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  • 1.
    Aaseth, Jan
    et al.
    Faculty of Health and Social Sciences, Inland Norway University of Applied Sciences, N-2624 Lillehammer, Norway.
    Alexander, Jan
    Norwegian Institute of Public Health, P.O. Box 222, N-0213 Oslo, Norway.
    Alehagen, Urban
    Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
    Tinkov, Alexey
    IM Sechenov First Moscow State Medical University (Sechenov University), Bolshaya Pirogovskaya St., 2-4, 119146 Moscow, Russia.
    Skalny, Anatoly
    IM Sechenov First Moscow State Medical University (Sechenov University), Bolshaya Pirogovskaya St., 2-4, 119146 Moscow, Russia.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Crisponi, Guido
    Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato-Cagliari, Italy.
    Nurchi, Valeria Marina
    Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato-Cagliari, Italy.
    The Aging Kidney-As Influenced by Heavy Metal Exposure and Selenium Supplementation2021In: Biomolecules, E-ISSN 2218-273X, Vol. 11, no 8, article id 1078Article in journal (Refereed)
    Abstract [en]

    The aging process in the kidneys has been well studied. It is known that the glomerular filtration rate (GFR) declines with age in subjects older than 50-60 years. However, there is still insufficient knowledge regarding the response of the aged kidney to environmental toxicants such as mercury, cadmium, and lead. Here, we present a review on the functional decline and proposed mechanisms in the aging kidney as influenced by metal pollutants. Due to the prevalence of these toxicants in the environment, human exposure is nearly unavoidable. Further, it is well known that acute and chronic exposures to toxic metals may be detrimental to kidneys of normal adults, thus it may be hypothesized that exposure of individuals with reduced GFR will result in additional reductions in renal function. Individuals with compromised renal function, either from aging or from a combination of aging and disease, may be particularly susceptible to environmental toxicants. The available data appear to show an association between exposure to mercury, cadmium and/or lead and an increase in incidence and severity of renal disease in elderly individuals. Furthermore, some physiological thiols, as well as adequate selenium status, appear to exert a protective action. Further studies providing improved insight into the mechanisms by which nephrotoxic metals are handled by aging kidneys, as well as possibilities of therapeutic protection, are of utmost importance.

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  • 2. Abedini, Sadollah
    et al.
    Holme, Ingar
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jardine, Alan
    Cole, Ed
    Maes, Bart
    Holdaas, Hallvard
    Cerebrovascular events in renal transplant recipients2009In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 87, no 1, p. 112-7Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The incidence of stroke and risk factors for different subtypes of cerebrovascular (CBV) events in renal transplant recipients have not been examined in any large prospective controlled trial. METHODS: The Assessment of Lescol in Renal Transplantation was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin (40-80 mg) daily on cardiovascular, and renal outcomes in renal transplant recipients. Patients initially randomized to fluvastatin or placebo in the 5 to 6 year trial was offered open-label fluvastatin in a 2-year extension to the original study. We investigated the incidence of stroke and risk factors for ischemic and hemorrhagic CBV events in 2102 renal graft recipients participating in the Assessment of Lescol in Renal Transplantation core and extension trial with a mean follow-up of 6.7 years. RESULTS: The incidence and type of CBV events did not differ between the lipid lowering arm and the placebo arm. A total of 184 (8.8%, 95% confidence interval 4.6-12.9) of 2102 patients experienced a CBV event during follow-up, corresponding to an incidence of 1.3% CBV event per year. The mortality for patients experiencing a hemorrhagic stroke was 48% (13 of 27), whereas the mortality for ischemic strokes was 6.0% (8 of 133). Diabetes mellitus, previous CBV event, age, and serum creatinine were independent risk factors for cerebral ischemic events. The risk of a hemorrhagic cerebral event was increased by diabetes mellitus, polycystic kidney disease, left ventricular hypertrophy, and systolic blood pressure. INTERPRETATION: Risk factors for CBV events in renal transplant recipients differ according to subtype.

  • 3. Abedini, Sadollah
    et al.
    Holme, Ingar
    März, Winfried
    Weihrauch, Gisela
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jardine, Alan
    Cole, Edward
    Maes, Bart
    Neumayer, Hans-Hellmut
    Grönhagen-Riska, Carola
    Ambühl, Patrice
    Holdaas, Halvard
    Inflammation in renal transplantation2009In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 4, no 7, p. 1246-1254Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: Renal transplant recipients experience premature cardiovascular disease and death. The association of inflammation, all-cause mortality, and cardiovascular events in renal transplant recipients has not been examined in a large prospective controlled trial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: ALERT was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin on cardiovascular and renal outcomes in 2102 renal transplant recipients. Patients initially randomized to fluvastatin or placebo in the 5- to 6-yr trial were offered open-label fluvastatin in a 2-yr extension to the original study. The association between inflammation markers, high-sensitivity C-reactive protein (hsCRP), and IL-6 on cardiovascular events and all-cause mortality was investigated. RESULTS: The baseline IL-6 value was 2.9 +/- 1.9 pg/ml (n = 1751) and that of hsCRP was 3.8 +/- 6.7 mg/L (n = 1910). After adjustment for baseline values for established risk factors, the hazard ratios for a major cardiac event and all-cause mortality for IL-6 were 1.08 [95% confidence interval (CI), 1.01 to 1.15, P = 0.018] and 1.11 (95% CI, 1.05 to 1.18, P < 0.001), respectively. The adjusted hazard ratio for hsCRP for a cardiovascular event was 1.10 (95% CI, 1.01 to 1.20, P = 0.027) and for all-cause mortality was 1.15 (95% CI, 1.06 to 1.1.25, P = 0.049). CONCLUSIONS: The inflammation markers IL-6 and hsCRP are independently associated with major cardiovascular events and all-cause mortality in renal transplant recipients.

  • 4. Abedini, Sadollah
    et al.
    Meinitzer, Andreas
    Holme, Ingar
    März, Winfried
    Weihrauch, Gisela
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jardine, Alan
    Holdaas, Halvard
    Asymmetrical dimethylarginine is associated with renal and cardiovascular outcomes and all-cause mortality in renal transplant recipients2010In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 77, no 1, p. 44-50Article in journal (Refereed)
    Abstract [en]

    Increased plasma levels of asymmetric dimethylarginine (ADMA) are associated with endothelial dysfunction and predict the progression to dialysis and death in patients with chronic kidney disease. The effects of these increased ADMA levels in renal transplant recipients, however, are unknown. We used the data from ALERT, a randomized, double-blind, placebo-controlled study of the effect of fluvastatin on cardiovascular and renal outcomes in 2102 renal transplant recipients with stable graft function on enrollment. Patients who were initially randomized to fluvastatin or placebo in the 5- to 6-year trial were offered open-label fluvastatin in a 2-year extension of the original study. After adjustment for baseline values for established factors in this post hoc analysis, ADMA was found to be a significant risk factor for graft failure or doubling of serum creatinine (hazard ratio 2.78), major cardiac events (hazard ratio 2.61), cerebrovascular events (hazard ratio 6.63), and all-cause mortality (hazard ratio 4.87). In this trial extension, the number of end points increased with increasing quartiles of plasma ADMA levels. All end points were significantly increased in the fourth compared to the first quartile. Our study shows that elevated plasma levels of ADMA are associated with increased morbidity, mortality, and the deterioration of graft function in renal transplant recipients.

  • 5.
    Acosta Ruiz, Vanessa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ladjevardi, Sam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Brekkan, Einar
    Uppsala University Hospital, Urology, Uppsala, Sweden.
    Häggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Lönnemark, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Periprocedural outcome after laparoscopic partial nephrectomy versus radiofrequency ablation for T1 renal tumors: A modified R.E.N.A.L nephrometry score adjusted comparison2019In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 60, no 2, p. 260-268Article in journal (Refereed)
    Abstract [en]

    Background: Comparable oncological outcomes have been seen after surgical nephrectomy and thermal ablation of renal tumors recently. However, periprocedural outcome needs to be assessed for aiding treatment decision.

    Purpose: To compare efficacy rates and periprocedural outcome (technical success, session time, hospitalization time, and complications) after renal tumor treatment with laparoscopic partial nephrectomy (LPN) or radiofrequency ablation (RFA).

    Material and Methods: The initial experience with 49 (treated with LPN) and 84 (treated with RFA) consecutive patients for a single renal tumor (diameter ≤ 5 cm, limited to the kidney) during 2007-2014 was evaluated. Patient and tumor characteristics, efficacy rates, and periprocedural outcome were collected retrospectively. The stratified Mantel Haenzel and Van Elteren tests, adjusted for tumor complexity (with the modified R.E.N.A.L nephrometry score [m-RNS]), were used to assess differences in treatment outcomes.

    Results: Primary efficacy rate was 98% for LPN and 85.7% for RFA; secondary efficacy rate was 93.9% for LPN and 95.2% for RFA; and technical success rate was 87.8% for LPN and 100% for RFA. Median session (m-RNS adjusted P < 0.001; LPN 215 min, RFA 137 min) and median hospitalization time were longer after LPN (m-RNS adjusted P < 0.001; LPN 5 days, RFA 2 days). Side effects were uncommon (LPN 2%, RFA 4.8%). Complications were more frequent after LPN (m-RNS adjusted P < 0.001; LPN 42.9%, RFA 10.7%).

    Conclusion: Both methods achieved equivalent secondary efficacy rates. RFA included several treatment sessions, but session and hospitalization times were shorter, and complications were less frequent than for LPN. The differences remained after adjustment for renal tumor complexity.

  • 6.
    Adamo, Hanibal
    et al.
    Umea Univ, Dept Med Biosci, Pathol, 6M, Umea, Sweden.
    Hammarsten, Peter
    Umea Univ, Dept Med Biosci, Pathol, 6M, Umea, Sweden.
    Hägglöf, Christina
    Umea Univ, Dept Med Biosci, Pathol, 6M, Umea, Sweden.
    Scherdin, Tove Dahl
    Umea Univ, Dept Med Biosci, Pathol, 6M, Umea, Sweden.
    Egevad, Lars
    Karolinska Univ Hosp, Dept Oncol Pathol, Stockholm, Sweden.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Bergström, Sofia Halin
    Umea Univ, Dept Med Biosci, Pathol, 6M, Umea, Sweden.
    Bergh, Anders
    Umea Univ, Dept Med Biosci, Pathol, 6M, Umea, Sweden.
    Prostate cancer induces C/EBP expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcome2019In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 79, no 5, p. 435-445Article in journal (Refereed)
    Abstract [en]

    Background: Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating adaptations in the tumor-bearing organ. Similar changes are seen in prostate cancer patients and they are related to outcome. One gene previously found to be upregulated in the non-malignant part of tumor-bearing prostate lobe in rats was the transcription factor CCAAT/enhancer-binding protein- (C/EBP).

    Methods: To explore this further, we examined C/EBP expression by quantitative RT-PCR, immunohistochemistry, and Western blot in normal rat prostate tissue surrounding slow-growing non-metastatic Dunning G, rapidly growing poorly metastatic (AT-1), and rapidly growing highly metastatic (MatLyLu) rat prostate tumors?and also by immunohistochemistry in a tissue microarray (TMA) from prostate cancer patients managed by watchful waiting.

    Results: In rats, C/EBP mRNA expression was upregulated in the surrounding tumor-bearing prostate lobe. In tumors and in the surrounding non-malignant prostate tissue, C/EBP was detected by immunohistochemistry in some epithelial cells and in infiltrating macrophages. The magnitude of glandular epithelial C/EBP expression in the tumor-bearing prostates was associated with tumor size, distance to the tumor, and metastatic capacity. In prostate cancer patients, high expression of C/EBP in glandular epithelial cells in the surrounding tumor-bearing tissue was associated with accumulation of M1 macrophages (iNOS+) and favorable outcome. High expression of C/EBP in tumor epithelial cells was associated with high Gleason score, high tumor cell proliferation, metastases, and poor outcome.

    Conclusions: This study suggest that the expression of C/EBP-beta, a transcription factor mediating multiple biological effects, is differentially expressed both in the benign parts of the tumor-bearing prostate and in prostate tumors, and that alterations in this may be related to patient outcome.

  • 7.
    Adams, Charleen
    et al.
    MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom.; University of Bristol, Bristol, United Kingdom..
    Richmond, Rebecca C.
    Santos Ferreira, Diana L
    Spiller, Wes
    Tan, Vanessa Y
    Zheng, Jie
    Wurtz, Peter
    Donovan, Jenny L
    Hamdy, Freddie C
    Neal, David E
    Lane, J Athene
    Davey Smith, George
    Relton, Caroline L
    Eeles, Rosalind A
    Henderson, Brian E
    Haiman, Christopher A
    Kote-Jarai, Zsofia
    Schumacher, Fredrick R
    Amin Al Olama, Ali
    Benlloch, Sara
    Muir, Kenneth
    Berndt, Sonja I
    Conti, David V
    Wiklund, Fredrik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden..
    Chanock, Stephen J
    Gapstur, Susan M
    Stevens, Victoria L
    Tangen, Catherine M
    Batra, Jyotsna
    Clements, Judith A
    Grönberg, Henrik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden..
    Pashayan, Nora
    Schleutker, Johanna
    Albanes, Demetrius
    Wolk, Alicja
    Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden..
    West, Catharine M L
    Mucci, Lorelei A
    Cancel-Tassin, Geraldine
    Koutros, Stella
    Sørensen, Karina D
    Maehle, Lovise
    Travis, Ruth C
    Hamilton, Robert
    Ingles, Sue Ann
    Rosenstein, Barry S
    Lu, Yong-Jie
    Giles, Graham G
    Kibel, Adam S
    Vega, Ana
    Kogevinas, Manolis
    Penney, Kathryn L
    Park, Jong Y
    Stanford, Janet L
    Cybulski, Cezary
    Nordestgaard, Borge G
    Brenner, Hermann
    Maier, Christiane
    Kim, Jeri
    John, Esther M
    Teixeira, Manuel R
    Neuhausen, Susan L
    DeRuyck, Kim
    Razack, Azad
    Newcomb, Lisa F
    Lessel, Davor
    Kaneva, Radka P
    Usmani, Nawaid
    Claessens, Frank
    Townsend, Paul
    Gago Dominguez, Manuela
    Roobol, Monique J
    Menegaux, Florence
    Khaw, Kay-Tee
    Cannon-Albright, Lisa A
    Pandha, Hardev
    Thibodeau, Stephen N
    Martin, Richard M
    Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study2019In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 28, no 1, p. 208-216Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer-metabolite associations using two-sample Mendelian randomization (MR).

    MATERIALS AND METHODS: The case-control portion of the study was conducted in nine UK centres with men aged 50-69 years who underwent prostate-specific antigen (PSA) screening for prostate cancer within the Prostate testing for cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium.

    RESULTS: Thirty-five metabolites were strongly associated with prostate cancer (p <0.0014, multiple-testing threshold). These fell into four classes: i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); ii) fatty acids and ratios; iii) amino acids; iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal.

    CONCLUSIONS: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk.

    IMPACT: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.

  • 8.
    Ahlberg, Mats Steinholtz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Surveillance and follow-up of early prostate cancer2024Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Active surveillance (AS) for prostate cancer was introduced to address overtreatment resulting from prostate-specific antigen (PSA) testing. Despite advancements such as Magnetic Resonance Imaging (MRI) and targeted biopsies, PSA remains crucial in prostate cancer diagnostics, leading to ongoing challenges of overdiagnosis and overtreatment. This thesis aimed to investigate different aspects of AS and follow-up of early prostate cancer and provide new insights to reduce overtreatment and enhance surveillance and follow-up. In Paper I, the rationale and methodology of a randomized controlled trial, the Prostate Cancer Active Surveillance Trigger trial/Scandinavian Prostate Cancer Group study no. 17 (PCASTt/SPCG17), were outlined. This trial's objective is to evaluate the safety of an AS protocol based on MRI and standardized triggers for repeat biopsies and transition to radical treatment. Patient recruitment is anticipated to conclude in 2024. Paper II investigated the risks of biochemical recurrence, metastatic disease, and prostate cancer-related death in patients following radical prostatectomy. The analysis was conditioned on time after radical prostatectomy without biochemical recurrence. For patients with favourable histopathology in prostatectomy specimens and no biochemical recurrence five years post-prostatectomy, the probability of developing metastatic disease or dying from prostate cancer within 20 years after surgery was very low. This suggests shorter follow-up for selected patients. Paper III compared outcomes of AS for men from different healthcare regions in Sweden with varying traditions of AS. Regions with lower uptake in AS demonstrated a higher probability of transitioning from AS to radical treatment, but no difference in AS failure. The results suggest overtreatment in regions with low uptake in AS. Paper IV explored the associations between potential triggers for transitioning from AS to radical treatment and the transition to treatment. We analysed how this association changed with the introduction of prostate MRI. We found an increasingly strong association between triggers, particularly histopathological progression, and transition. However, most treated men had not experienced histopathological progression. The introduction of MRI did not contribute much to the change. In conclusion, this thesis outlines an ongoing study on defined triggers for transitioning from AS to radical treatment, suggests shorter follow-up after radical prostatectomy for selected patients, reveals overtreatment in regions with low uptake in AS, and shows an increasing use of histopathological progression as a trigger for transition to radical treatment.

    List of papers
    1. PCASTt/SPCG-17-a randomised trial of active surveillance in prostate cancer: rationale and design
    Open this publication in new window or tab >>PCASTt/SPCG-17-a randomised trial of active surveillance in prostate cancer: rationale and design
    Show others...
    2019 (English)In: BMJ Open, E-ISSN 2044-6055, Vol. 9, no 8Article in journal (Refereed) Published
    Abstract [en]

    Introduction Overtreatment of localised prostate cancer is substantial despite increased use of active surveillance. No randomised trials help define how to monitor patients or when to initiate treatment with curative intent. Methods and analysis A randomised, multicentre, intervention trial designed to evaluate the safety of an MRI-based active surveillance protocol, with standardised triggers for repeated biopsies and radical treatment. The aim is to reduce overtreatment of prostate cancer. 2000 men will be randomly allocated to either surveillance according to current practice or to standardised triggers at centres in Sweden, Norway, Finland and the UK. Men diagnosed in the past 12 months with prostate cancer, <= T2a, prostate-specific antigen (PSA) <15ng/mL, PSA density <less than or equal to>0.2ng/mL/cc, any International Society of Urological Pathology (ISUP) grade 1 are eligible. Men with ISUP grade 2 in <30% of cores on systematic biopsy and <10mm cancer in one core on systematic or targeted biopsy are also eligible. Men diagnosed on systematic biopsy should have an MRI and targeted biopsies against Prostate Imaging and Reporting Data System V.2 3-5 lesions before inclusion. Identical follow-up in the two study arms: biannual PSA testing, yearly clinical examination and MRI every second year. In the experimental arm, standardised triggers based on MRI and PSA density elicit repeated biopsies. MRI and histopathological progression trigger radical treatment. Primary outcome measure is progression-free survival. Secondary outcome measures are cumulative incidence of metastatic disease, treatments with curative intent, pT3-4 at radical prostatectomy, switch to watchful waiting, prostate cancer mortality and quality of life. Inclusion started in October 2016 and in October 2018; 275 patients have been enrolled. Ethics and dissemination Ethical approval was obtained in each participating country. Results for the primary and secondary outcome measures will be submitted for publication in peer-reviewed journals. Trial registration number NCT02914873.

    Place, publisher, year, edition, pages
    BMJ PUBLISHING GROUP, 2019
    Keywords
    active surveillance, MRI, prostate cancer, randomised trial
    National Category
    Urology and Nephrology
    Identifiers
    urn:nbn:se:uu:diva-401175 (URN)10.1136/bmjopen-2018-027860 (DOI)000502537200134 ()31444180 (PubMedID)
    Funder
    Swedish Cancer Society, 2016/466Swedish Cancer Society, 2014/1275Swedish Research Council, 2016-00177Swedish Research Council, 2016-01293
    Available from: 2020-01-07 Created: 2020-01-07 Last updated: 2023-12-06Bibliographically approved
    2. Time without PSA recurrence after radical prostatectomy as a predictor of future biochemical recurrence, metastatic disease and prostate cancer death: a prospective Scandinavian cohort study
    Open this publication in new window or tab >>Time without PSA recurrence after radical prostatectomy as a predictor of future biochemical recurrence, metastatic disease and prostate cancer death: a prospective Scandinavian cohort study
    Show others...
    2022 (English)In: BMJ Open, E-ISSN 2044-6055, Vol. 12, no 12, article id e057242Article in journal (Refereed) Published
    Abstract [en]

    Objective: Although surveillance after radical prostatectomy routinely includes repeated prostate specific antigen (PSA)-testing for many years, biochemical recurrence often occurs without further clinical progression. We therefore hypothesised that follow-up can be shortened for many patients without increasing the risk of prostate cancer death. We investigated the long-term probabilities of PSA recurrence, metastases and prostate cancer death in patients without biochemical recurrence five and 10 years after radical prostatectomy.

    Design: Prospective cohort study. Stratification by Gleason score (<= 3+4=7or >= 4+3=7), pathological tumour stage (pT2 or >= pT3) and negative or positive surgical margins.

    Setting: Between 1989 and 1998, 14 urological centres in Scandinavia randomised patients to the Scandinavian Prostate Cancer Group study number 4 (SPCG-4) trial.ParticipationAll 306 patients from the SPCG-4 trial who underwent radical prostatectomy within 1year from inclusion were eligible. Four patients were excluded due to surgery-related death (n=1) or salvage radiotherapy or hormonal treatment within 6weeks from surgery (n=3).

    Primary outcome measures: Cumulative incidences and absolute differences in metastatic disease and prostate cancer death.

    Results: We analysed 302 patients with complete follow-up during a median of 24 years. Median preoperative PSA was 9.8ng/mL and median age was 65 years. For patients without biochemical recurrence 5 years after radical prostatectomy the 20-year probability of biochemical recurrence was 25% among men with Gleason score <= 3+4=7and 57% among men with Gleason score >= 4+3=7; the probabilities for metastases were 0.8% and 17%; and for prostate cancer death 0.8% and 12%, respectively. The long-term probabilities were higher for pT >= 3versus pT2 and for positive versus negative surgical margins. Limitations include small size of the cohort.

    Conclusion: Many patients with favourable histopathology without biochemical recurrence 5years after radical prostatectomy could stop follow-up earlier than 10 years after radical prostatectomy.

    Place, publisher, year, edition, pages
    BMJ Publishing Group Ltd, 2022
    Keywords
    Prostate disease, Urological tumours, Epidemiology
    National Category
    Urology and Nephrology Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-497720 (URN)10.1136/bmjopen-2021-057242 (DOI)000924517900003 ()36581423 (PubMedID)
    Funder
    Swedish Cancer Society, 2016/466Swedish Cancer Society, 2014/1275Swedish Research Council, 2016-00177Swedish Research Council, 2016-01293ProstatacancerförbundetPercy Falks stiftelse för forskning beträffande prostatacancer och bröstcancer
    Available from: 2023-03-07 Created: 2023-03-07 Last updated: 2023-12-06Bibliographically approved
    3. Variations in the Uptake of Active Surveillance for Prostate Cancer and Its Impact on Outcomes
    Open this publication in new window or tab >>Variations in the Uptake of Active Surveillance for Prostate Cancer and Its Impact on Outcomes
    2023 (English)In: European Urology Open Science, ISSN 2666-1691, E-ISSN 2666-1683, Vol. 52, p. 166-173Article in journal (Refereed) Published
    Abstract [en]

    Background: Regional differences in active surveillance (AS) uptake for prostate cancer (PC) illustrate an inequality in treatment strategies.

    Objective: To examine the association between regional differences in AS uptake and transition to radical treatment, start of androgen deprivation therapy (ADT), watchful waiting, or death.

    Design, setting, and participants: A Swedish population-based cohort study was con-ducted including men in the National Prostate Cancer Register in Sweden with low -risk or favorable intermediate-risk PC, starting AS from January 1, 2007 and continuing till December 31, 2019.

    Intervention: Regional tradition of low, intermediate, or high proportions of immediate radical treatment. Outcomes measurements and statistical analysis:Probabilities of transition from AS to radical treatment, start of ADT, watchful waiting, or death from other causes were assessed.

    Results and limitations: We included 13 679 men. The median age was 66 yr, median PSA 5.1 ng/ml, and median follow-up 5.7 yr. Men from regions with a high AS uptake had a lower probability of transition to radical treatment (36%) than men from regions with a low AS uptake (40%; absolute difference 4.1%; 95% confidence interval [CI] 1.0-7.2), but not a higher probability of AS failure defined as the start of ADT (absolute difference 0.4%; 95% CI -0.7 to 1.4). There were no statistically significant differences in the probability of transition to watchful waiting or death from other causes. Limitations include uncertainty in the estimation of remaining lifetime and transition to watchful waiting.

    Conclusions:A regional tradition of a high AS uptake is associated with a lower probability of transition to radical treatment, but not with AS failure. A low AS uptake suggests overtreatment.

    Place, publisher, year, edition, pages
    Elsevier BV, 2023
    Keywords
    Active surveillance, Prostate cancer, Outcomes, Overtreatment
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-509996 (URN)10.1016/j.euros.2023.04.006 (DOI)001043792000001 ()37284040 (PubMedID)
    Funder
    Swedish Cancer Society, 190020ProstatacancerförbundetPercy Falks stiftelse för forskning beträffande prostatacancer och bröstcancerStiftelsen Hillevi Fries forskningsfond
    Available from: 2023-08-28 Created: 2023-08-28 Last updated: 2023-12-06Bibliographically approved
    4. Triggers for transition from active surveillance to radical treatment of prostate cancer 2008-2020 – a case control study
    Open this publication in new window or tab >>Triggers for transition from active surveillance to radical treatment of prostate cancer 2008-2020 – a case control study
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: What should trigger transition from active surveillance (AS) to radical treatment for prostate cancer (PC) remains an unanswered question. 

    Objective:To examine the association between potential triggers and transition from AS to radical treatment.Design, Setting and Participants:Swedish register-based case-control study including men in the National Prostate Cancer Register in Sweden with low- or favorable intermediate-risk PC, starting AS from Jan 1st, 2008, to Dec 31st, 2020.

    Interventions: Triggers are: histopathological progression, MRI progression without histopathological progression, and only PSA progression.

    Outcomes measurements and statistical analysis: Probability of experiencing a trigger one year preceding treatment. Odds ratios (OR) of histopathological progression, MRI progression without histopathological progression, or only PSA progression, for transition to radical treatment, analyzed by logistic regression.

    Results and limitations: The study base included 846 patients, 99 cases 2008-2014, and 172 cases 2015-2020. For every case, 10 controls were chosen. Histopathological progression was strongly associated with transition to radical treatment (OR 2008-2014: 6.89, 95% confidence interval (CI) 3.78-12.56; 2015-2020: 65.03, 95% CI 35.11-120.44). MRI progression was associated with treatment 2015-2020 (adjusted OR 4.01, 95% CI 1.72-9.36) but PSA progression was not associated with treatment in any adjusted analyses. Absence of any progression was strongly associated with reduced probability of transition to treatment (adjusted OR 2008-2014: 0.24, 95% CI 0.15-0.39, adjusted OR 2015-2020: 0.08, 95% CI 0.05-0.12) but the probability of treated men not having experienced any trigger was still 27% 2015-2020. Limitations include small study-base.

    Conclusion: Histopathological progression during AS was increasingly strongly associated with transition to treatment but the probability of not having experienced any trigger before treatment was 27%.

    Patient summary: Reliance on objective signs of progression before discontinuing AS increase, but still about a quarter of treated men have not experienced progression.

    Keywords
    Prostate cancer, Active surveillance, Triggers
    National Category
    Urology and Nephrology Cancer and Oncology
    Research subject
    Urology
    Identifiers
    urn:nbn:se:uu:diva-515871 (URN)
    Available from: 2023-11-13 Created: 2023-11-13 Last updated: 2023-12-06
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  • 9.
    Ahlberg, Mats Steinholtz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Triggers for transition from active surveillance to radical treatment of prostate cancer 2008-2020 – a case control studyManuscript (preprint) (Other academic)
    Abstract [en]

    Background: What should trigger transition from active surveillance (AS) to radical treatment for prostate cancer (PC) remains an unanswered question. 

    Objective:To examine the association between potential triggers and transition from AS to radical treatment.Design, Setting and Participants:Swedish register-based case-control study including men in the National Prostate Cancer Register in Sweden with low- or favorable intermediate-risk PC, starting AS from Jan 1st, 2008, to Dec 31st, 2020.

    Interventions: Triggers are: histopathological progression, MRI progression without histopathological progression, and only PSA progression.

    Outcomes measurements and statistical analysis: Probability of experiencing a trigger one year preceding treatment. Odds ratios (OR) of histopathological progression, MRI progression without histopathological progression, or only PSA progression, for transition to radical treatment, analyzed by logistic regression.

    Results and limitations: The study base included 846 patients, 99 cases 2008-2014, and 172 cases 2015-2020. For every case, 10 controls were chosen. Histopathological progression was strongly associated with transition to radical treatment (OR 2008-2014: 6.89, 95% confidence interval (CI) 3.78-12.56; 2015-2020: 65.03, 95% CI 35.11-120.44). MRI progression was associated with treatment 2015-2020 (adjusted OR 4.01, 95% CI 1.72-9.36) but PSA progression was not associated with treatment in any adjusted analyses. Absence of any progression was strongly associated with reduced probability of transition to treatment (adjusted OR 2008-2014: 0.24, 95% CI 0.15-0.39, adjusted OR 2015-2020: 0.08, 95% CI 0.05-0.12) but the probability of treated men not having experienced any trigger was still 27% 2015-2020. Limitations include small study-base.

    Conclusion: Histopathological progression during AS was increasingly strongly associated with transition to treatment but the probability of not having experienced any trigger before treatment was 27%.

    Patient summary: Reliance on objective signs of progression before discontinuing AS increase, but still about a quarter of treated men have not experienced progression.

  • 10.
    Ahlberg, Mats Steinholtz
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Adami, Hans-Olov
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden;Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
    Beckmann, Kerri
    Kings Coll London, Translat Oncol & Urol Res, London, England;Univ Southern Australia, Ctr Populat Hlth Res, Adelaide, SA, Australia.
    Bertilsson, Helena
    Univ Sykehuset Trondheim, Dept Urol, Sankt Olavs Hosp, Trondheim, Norway;NTNU Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, Trondheim, Norway.
    Bratt, Ola
    Goteborgs Univ Sahlgrenska Akad, Dept Urol, Gothenburg, Sweden.
    Cahill, Declan
    Royal Mardsen Hosp, London, England.
    Egevad, Lars
    Karolinska Univ Sjukhuset, Stockholm, Sweden.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Kings Coll London, Sch Canc & Pharmaceut Sci, London, England;.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Kings Coll London, Div Canc Studies, Sch Med, London, England.
    Johansson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Rannikko, Antti
    Univ Helsinki, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland.
    Van Hemelrijck, Mieke
    Kings Coll London, Translat Oncol Off, London, England;Kings Coll London, Translat Urol Off, London, England.
    Jaderling, Fredrik
    Karolinska Univ Sjukhuset, Dept Radiol, Stockholm, Sweden;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Wassberg, Cecilia
    Karolinska Univ Sjukhuset, Dept Radiol, Stockholm, Sweden.
    Åberg, Ulrika W. N.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    PCASTt/SPCG-17-a randomised trial of active surveillance in prostate cancer: rationale and design2019In: BMJ Open, E-ISSN 2044-6055, Vol. 9, no 8Article in journal (Refereed)
    Abstract [en]

    Introduction Overtreatment of localised prostate cancer is substantial despite increased use of active surveillance. No randomised trials help define how to monitor patients or when to initiate treatment with curative intent. Methods and analysis A randomised, multicentre, intervention trial designed to evaluate the safety of an MRI-based active surveillance protocol, with standardised triggers for repeated biopsies and radical treatment. The aim is to reduce overtreatment of prostate cancer. 2000 men will be randomly allocated to either surveillance according to current practice or to standardised triggers at centres in Sweden, Norway, Finland and the UK. Men diagnosed in the past 12 months with prostate cancer, <= T2a, prostate-specific antigen (PSA) <15ng/mL, PSA density <less than or equal to>0.2ng/mL/cc, any International Society of Urological Pathology (ISUP) grade 1 are eligible. Men with ISUP grade 2 in <30% of cores on systematic biopsy and <10mm cancer in one core on systematic or targeted biopsy are also eligible. Men diagnosed on systematic biopsy should have an MRI and targeted biopsies against Prostate Imaging and Reporting Data System V.2 3-5 lesions before inclusion. Identical follow-up in the two study arms: biannual PSA testing, yearly clinical examination and MRI every second year. In the experimental arm, standardised triggers based on MRI and PSA density elicit repeated biopsies. MRI and histopathological progression trigger radical treatment. Primary outcome measure is progression-free survival. Secondary outcome measures are cumulative incidence of metastatic disease, treatments with curative intent, pT3-4 at radical prostatectomy, switch to watchful waiting, prostate cancer mortality and quality of life. Inclusion started in October 2016 and in October 2018; 275 patients have been enrolled. Ethics and dissemination Ethical approval was obtained in each participating country. Results for the primary and secondary outcome measures will be submitted for publication in peer-reviewed journals. Trial registration number NCT02914873.

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  • 11.
    Ahlberg, Mats Steinholtz
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Adami, Hans-Olov
    Univ Oslo, Inst Hlth & Soc, Clin Effectiveness Grp, Oslo, Norway.;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Andren, Ove
    Örebro Univ, Fac Med & Hlth, Dept Urol, Örebro, Sweden..
    Johansson, Jan-Erik
    Örebro Univ, Fac Med & Hlth, Dept Urol, Örebro, Sweden..
    Steineck, Gunnar
    Univ Gothenburg, Inst Clin Sci, Dept Oncol, Div Clin Canc Epidemiol,Sahlgrenska Acad, Gothenburg, Sweden..
    Holmberg, Lars
    Kings Coll London, Sch Canc & Pharmaceut Sci, London, England..
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Time without PSA recurrence after radical prostatectomy as a predictor of future biochemical recurrence, metastatic disease and prostate cancer death: a prospective Scandinavian cohort study2022In: BMJ Open, E-ISSN 2044-6055, Vol. 12, no 12, article id e057242Article in journal (Refereed)
    Abstract [en]

    Objective: Although surveillance after radical prostatectomy routinely includes repeated prostate specific antigen (PSA)-testing for many years, biochemical recurrence often occurs without further clinical progression. We therefore hypothesised that follow-up can be shortened for many patients without increasing the risk of prostate cancer death. We investigated the long-term probabilities of PSA recurrence, metastases and prostate cancer death in patients without biochemical recurrence five and 10 years after radical prostatectomy.

    Design: Prospective cohort study. Stratification by Gleason score (<= 3+4=7or >= 4+3=7), pathological tumour stage (pT2 or >= pT3) and negative or positive surgical margins.

    Setting: Between 1989 and 1998, 14 urological centres in Scandinavia randomised patients to the Scandinavian Prostate Cancer Group study number 4 (SPCG-4) trial.ParticipationAll 306 patients from the SPCG-4 trial who underwent radical prostatectomy within 1year from inclusion were eligible. Four patients were excluded due to surgery-related death (n=1) or salvage radiotherapy or hormonal treatment within 6weeks from surgery (n=3).

    Primary outcome measures: Cumulative incidences and absolute differences in metastatic disease and prostate cancer death.

    Results: We analysed 302 patients with complete follow-up during a median of 24 years. Median preoperative PSA was 9.8ng/mL and median age was 65 years. For patients without biochemical recurrence 5 years after radical prostatectomy the 20-year probability of biochemical recurrence was 25% among men with Gleason score <= 3+4=7and 57% among men with Gleason score >= 4+3=7; the probabilities for metastases were 0.8% and 17%; and for prostate cancer death 0.8% and 12%, respectively. The long-term probabilities were higher for pT >= 3versus pT2 and for positive versus negative surgical margins. Limitations include small size of the cohort.

    Conclusion: Many patients with favourable histopathology without biochemical recurrence 5years after radical prostatectomy could stop follow-up earlier than 10 years after radical prostatectomy.

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  • 12.
    Ahmad, Shafqat
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Harvard Med Sch, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA..
    Arnlov, Johan
    Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc NVS, S-14152 Stockholm, Sweden.;Dalarna Univ, Sch Hlth & Social Studies, S-79131 Falun, Sweden..
    Larsson, Susanna C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Medical epidemiology. Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, S-17177 Stockholm, Sweden.;Uppsala Univ, Dept Surg Sci, Unit Med Epidemiol, S-75185 Uppsala, Sweden..
    Genetically Predicted Circulating Copper and Risk of Chronic Kidney Disease: A Mendelian Randomization Study2022In: Nutrients, E-ISSN 2072-6643, Vol. 14, no 3, p. 509-, article id 509Article in journal (Refereed)
    Abstract [en]

    Elevated circulating copper levels have been associated with chronic kidney disease (CKD), kidney damage, and decline in kidney function. Using a two sample Mendelian randomization approach where copper-associated genetic variants were used as instrumental variables, genetically predicted higher circulating copper levels were associated with higher CKD prevalence (odds ratio 1.17; 95% confidence interval 1.04, 1.32; p-value = 0.009). There was suggestive evidence that genetically predicted higher copper was associated with a lower estimated glomerular filtration rate and a more rapid kidney damage decline. In conclusion, we observed that elevated circulating copper levels may be a causal risk factor for CKD.

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    FULLTEXT01
  • 13.
    Ajalloueian, Fatemeh
    et al.
    Tech Univ Denmark, DTU Food, Nanobio Sci Res Grp, Lyngby, Denmark.
    Lemon, Greg
    Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.
    Hilborn, Jöns
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Chronakis, Ioannis S.
    Tech Univ Denmark, DTU Food, Nanobio Sci Res Grp, Lyngby, Denmark.
    Fossum, Magdalena
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden; Karolinska Inst, Ctr Mol Med, CMM 02, Stockholm, Sweden; Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Dept Paediat Surg, Sect Urol, Stockholm, Sweden.
    Bladder biomechanics and the use of scaffolds for regenerative medicine in the urinary bladder2018In: Nature reviews. Urology, ISSN 1759-4812, E-ISSN 1759-4820, Vol. 15, no 3, p. 155-174Article, review/survey (Refereed)
    Abstract [en]

    The urinary bladder is a complex organ with the primary functions of storing urine under low and stable pressure and micturition. Many clinical conditions can cause poor bladder compliance, reduced capacity, and incontinence, requiring bladder augmentation or use of regenerative techniques and scaffolds. To replicate an organ that is under frequent mechanical loading and unloading, special attention towards fulfilling its biomechanical requirements is necessary. Several biological and synthetic scaffolds are available, with various characteristics that qualify them for use in bladder regeneration in vitro and in vivo, including in the treatment of clinical conditions. The biomechanical properties of the native bladder can be investigated using a range of mechanical tests for standardized assessments, as well as mathematical and computational bladder biomechanics. Despite a large body of research into tissue engineering of the bladder wall, some features of the native bladder and the scaffolds used to mimic it need further elucidation. Collection of comparable reference data from different animal models would be a helpful tool for researchers and will enable comparison of different scaffolds in order to optimize characteristics before entering preclinical and clinical trials.

  • 14.
    Akre, Olof
    et al.
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Garmo, Hans
    Regional Oncological Center, Uppsala, Sweden.
    Adolfsson, Jan
    Oncological Center, CLINTEC Department, Karolinska Institutet, Stockholm, Sweden.
    Lambe, Mats
    Oncological Center, CLINTEC Department, andDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Bratt, Ola
    Department of Urology, Helsingborg Hospital, Lund University, Sweden.
    Stattin, Pär
    Department of Surgical and Perioperative sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
    Mortality Among Men with Locally Advanced Prostate Cancer Managed with Noncurative Intent: A Nationwide Study in PCBaSe Sweden2011In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 60, no 3, p. 554-563Article in journal (Refereed)
    Abstract [en]

    Background

    There are limited prognostic data for locally advanced prostate cancer PCa to guide in the choice of treatment.

    Objective

    To assess mortality in different prognostic categories among men with locally advanced PCa managed with noncurative intent.

    Design, setting, and participants

    We conducted a register-based nationwide cohort study within the Prostate Cancer DataBase Sweden. The entire cohort of locally advanced PCa included 14 908 men. After the exclusion of 2724 (18%) men treated with curative intent, 12 184 men with locally advanced PCa either with local clinical stage T3 or T4 or with T2 with serum levels of prostate-specific antigen (PSA) between 50 and 99 ng/ml and without signs of metastases remained for analysis.

    Measurements

    We followed up the patient cohort in the Cause of Death Register for ≤11 yr and assessed cumulative incidence of PCa -specific death stratified by age and clinical characteristics.

    Results and limitations

    The PCa -specific mortality at 8 yr of follow-up was 28% (95% confidence interval [CI], 25–32%) for Gleason score (GS) 2–6, 41% (95% CI, 38–44%) for GS 7, 52% (95% CI, 47–57%) for GS 8, and 64% (95% CI, 59–69%) for GS 9–10. Even for men aged >85 yr at diagnosis with GS 8–10, PCa was a major cause of death: 42% (95% CI, 37–47%). Men with locally advanced disease and a PSA < 4 ng/ml at diagnosis were at particularly increased risk of dying from PCa. One important limitation is the lack of bone scans in 42% of the patient cohort, but results remained after exclusion of patients with unknown metastasis status.

    Conclusions

    The PCa-specific mortality within 8 yr of diagnosis is high in locally advanced PCa, suggesting undertreatment, particularly among men in older age groups. Our results underscore the need for more studies of treatment with curative intent for locally advanced tumors.

  • 15.
    Al Ahmadi, Ibrahim
    et al.
    King Faisal Hosp & Res Ctr, Organ Transplant Ctr, Riyadh, Saudi Arabia..
    Abasi, Amira
    King Faisal Hosp & Res Ctr, Organ Transplant Ctr, Riyadh, Saudi Arabia..
    Syed, Raza
    King Faisal Hosp & Res Ctr, Organ Transplant Ctr, Riyadh, Saudi Arabia..
    Broering, Dieter-C.
    King Faisal Hosp & Res Ctr, Organ Transplant Ctr, Riyadh, Saudi Arabia..
    Biglarnia, Ali-Reza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Initial Experience From Implementation of Hand-Assisted Retroperitoneoscopic Live Donor Nephrectomy in Saudi Arabia2013In: Annals of Saudi Medicine, ISSN 0256-4947, E-ISSN 0975-4466, Vol. 33, no 2, p. S58-S59Article in journal (Refereed)
    Abstract [en]

    Introduction: Donor risks and morbidity are consequences of the invasiveness of donor nephrectomy procedure. The flank incision is currently the default donor nephrectomy procedure at the King Faisal Hospital in Saudi Arabia. In order to minimize the surgical-related trauma, we are implementing the hand-assisted retroperitoneoscopic live donor nephrectomy (HARS), which previously has been shown to promote donor safety. Here, we present our initial experience with this procedure. Material and Methods: The HARS technique was implemented at our center in 2010. We present a survey of our data regarding operative characteristics as well as donor/recipient outcome. Given the small number of cases, data are presented as median with range. Results: Between 2010 and 2013, 18 left -sided HARS nephrectomy procedures were performed. The median donor age and BMI were 26.5 (18-43) and 24.1 (18.7-30.7), respectively. The median hospitalization was 4 days (3-5). One donor presented wound seroma in the pfannenstiell incision with no need for intervention. Another donor presented unspecific thoracoabdominal pain on postoperative day 2. No intra-and postoperative bleeding was observed. The median creatinine at the current follow-up was 90 mu mol/L with 100% graft survival. Conclusion: HARS is a feasible and safe technique. However, for implementation of HARS as the default donor nephrectomy procedure more practice is needed.

  • 16.
    Albert, Christian
    et al.
    Otto von Guericke Univ, Univ Clin Cardiol & Angiol, Med Fac, Magdeburg, Germany.;Diaverum Renal Serv Germany, MVZ Neuen Garten 11, D-14469 Potsdam, Germany..
    Zapf, Antonia
    Univ Med Ctr Hamburg Eppendorf, Dept Med Biometry & Epidemiol, Hamburg, Germany..
    Haase, Michael
    Otto von Guericke Univ, Fac Med, Magdeburg, Germany.;Diaverum Renal Serv Germany, MVZ Neuen Garten 11, D-14469 Potsdam, Germany..
    Rover, Christian
    Univ Med Ctr Gottingen, Dept Med Stat, Gottingen, Germany..
    Pickering, John W.
    Univ Otago Christchurch, Dept Med, Christchurch, New Zealand.;Christchurch Hosp, Emergency Dept, Christchurch, New Zealand..
    Albert, Annemarie
    Diaverum Renal Serv Germany, MVZ Neuen Garten 11, D-14469 Potsdam, Germany.;Klinikum Ernst von Bergmann, Dept Nephrol & Endocrinol, Potsdam, Germany..
    Bellomo, Rinaldo
    Austin Hosp, Dept Intens Care, Melbourne, Vic, Australia.;Univ Melbourne, Ctr Integrated Crit Care, Melbourne, Vic, Australia..
    Breidthardt, Tobias
    Univ Hosp Basel, Dept Internal Med, Basel, Switzerland.;Univ Hosp Basel, Dept Nephrol, Basel, Switzerland.;Univ Hosp Basel, Dept Cardiol, Basel, Switzerland..
    Camou, Fabrice
    CHU Bordeaux, Hop St Andre, Serv Reanimat Med, Bordeaux, France..
    Chen, Zhongquing
    Southern Med Univ, Nanfang Hosp, Dept Crit Care Med, Guangzhou, Guangdong, Peoples R China..
    Chocron, Sidney
    Univ Hosp Jean Minjoz, Dept Thorac & Cardiovasc Surg, Besancon, France..
    Cruz, Dinna
    Univ Calif San Diego, Div Nephrol Hypertens, San Diego, CA 92103 USA..
    de Geus, Hilde R. H.
    Erasmus MC, Dept Intens Care, Rotterdam, Netherlands..
    Devarajan, Prasad
    Univ Cincinnati, Div Nephrol & Hypertens, Cincinnati Childrens Hosp, Cincinnati, OH USA..
    Di Somma, Salvatore
    Univ Rome, Dept Med Surg Sci & Translat Med, Emergency Med, S Andrea Hosp, Rome, Italy..
    Doi, Kent
    Univ Tokyo, Dept Emergency & Crit Care Med, Tokyo, Japan..
    Endre, Zoltan H.
    Univ New South Wales, Prince Wales Hosp, Dept Nephrol, Sydney, NSW, Australia.;Univ New South Wales, Clin Sch, Dept Nephrol, Sydney, NSW, Australia..
    Garcia-Alvarez, Mercedes
    Hosp Santa Creu Sant & Pau, Dept Anesthesiol, Barcelona, Spain..
    Hjortrup, Peter B.
    Copenhagen Univ Hosp, Dept Intens Care, Copenhagen, Denmark..
    Hur, Mina
    Konkuk Univ, Dept Lab Med, Sch Med, Seoul, South Korea..
    Karaolanis, Georgios
    Natl & Kapodistrian Univ Athens, Med Sch, Laiko Gen Hosp, Vasc Unit,Dept Surg 1, Athens, Greece..
    Kavalci, Cemil
    Baskent Univ, Emergency Dept, Fac Med, Ankara, Turkey..
    Kim, Hanah
    Konkuk Univ, Dept Lab Med, Sch Med, Seoul, South Korea..
    Lentini, Paolo
    San Bassiano Hosp, Dept Nephrol & Dialysis, Bassano Del Grappa, Italy..
    Liebetrau, Christoph
    Kerckhoff Clin, Dept Cardiol, Bad Nauheim, Germany..
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Martensson, Johan
    Karolinska Inst, Sect Anaesthesia & Intens Care Med, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Mueller, Christian
    Univ Hosp Basel, Dept Internal Med, Basel, Switzerland.;Univ Hosp Basel, Dept Nephrol, Basel, Switzerland.;Univ Hosp Basel, Dept Cardiol, Basel, Switzerland..
    Nanas, Serafim
    Natl & Kapodistrian Univ Athens, Evangelismos Gen Hosp, Crit Care Dept 1, Athens, Greece..
    Nickolas, Thomas L.
    Columbia Univ, Vagelos Coll Phys & Surg, New York, NY USA..
    Pipili, Chrysoula
    Natl & Kapodistrian Univ Athens, Evangelismos Gen Hosp, Crit Care Dept 1, Athens, Greece..
    Ronco, Claudio
    Univ Padua, Nephrol Dialysis & Transplantat, Padua, Italy.;San Bortolo Hosp, Int Renal Res Inst, Vicenza, Italy..
    Rosa-Diez, Guillermo J.
    Hosp Italiano Buenos Aires, Dept Nephrol Dialysis & Transplantat, Buenos Aires, DF, Argentina..
    Ralib, Azrina
    Int Islamic Univ Malaysia, Dept Anaesthesiol & Intens Care, Pahang, Malaysia..
    Soto, Karina
    Hosp Fernando Fonseca, Dept Nephrol, Amadora, Portugal.;Univ Lisbon, Ctr Estat & Aplicacoes, CEAUL, Lisbon, Portugal..
    Braun-Dullaeus, Ruediger C.
    Otto von Guericke Univ, Univ Clin Cardiol & Angiol, Med Fac, Magdeburg, Germany..
    Heinz, Judith
    Univ Med Ctr Gottingen, Dept Med Stat, Gottingen, Germany..
    Haase-Fielitz, Anja
    Univ Potsdam, Brandenburg Med Sch Theodor Fontane, Immanuel Diakonie Bernau, Heart Ctr Brandenburg,Dept Cardiol,Fac Hlth Sci, Potsdam, Germany..
    Neutrophil Gelatinase-Associated Lipocalin Measured on Clinical Laboratory Platforms for the Prediction of Acute Kidney Injury and the Associated Need for Dialysis Therapy: A Systematic Review and Meta-analysis2020In: American Journal of Kidney Diseases, ISSN 0272-6386, E-ISSN 1523-6838, Vol. 76, no 6, p. 826-+Article, review/survey (Refereed)
    Abstract [en]

    Rationale & Objective: The usefulness of measures of neutrophil gelatinase-associated lipocalin (NGAL) in urine or plasma obtained on clinical laboratory platforms for predicting acute kidney injury (AKI) and AKI requiring dialysis (AKI-D) has not been fully evaluated. We sought to quantitatively summarize published data to evaluate the value of urinary and plasma NGAL for kidney risk prediction.

    Study Design: Literature-based meta-analysis and individual-study-data meta-analysis of diagnostic studies following PRISMA-IPD guidelines.

    Setting & Study Populations: Studies of adults investigating AKI, severe AKI, and AKI-D in the setting of cardiac surgery, intensive care, or emergency department care using either urinary or plasma NGAL measured on clinical laboratory platforms.

    Selection Criteria for Studies: PubMed, Web of Science, Cochrane Library, Scopus, and congress abstracts ever published through February 2020 reporting diagnostic test studies of NGAL measured on clinical laboratory platforms to predict AKI.

    Data Extraction: Individual-study-data meta analysis was accomplished by giving authors data specifications tailored to their studies and requesting standardized patient-level data analysis.

    Analytical Approach: Individual-study-data meta analysis used a bivariate time-to-event model for interval-censored data from which discriminative ability (AUC) was characterized. NGAL cutoff concentrations at 95% sensitivity, 95% specificity, and optimal sensitivity and specificity were also estimated. Models incorporated as confounders the clinical setting and use versus nonuse of urine output as a criterion for AKI. A literature-based meta-analysis was also performed for all published studies including those for which the authors were unable to provide individual-study data analyses.

    Results: We included 52 observational studies involving 13,040 patients. We analyzed 30 data sets for the individual-study-data meta-analysis. For AKI, severe AKI, and AKI-D, numbers of events were 837, 304, and 103 for analyses of urinary NGAL, respectively; these values were 705, 271, and 178 for analyses of plasma NGAL. Discriminative performance was similar in both meta-analyses. Individual-study-data meta-analysis AUCs for urinary NGAL were 0.75 (95% CI, 0.73-0.76) and 0.80 (95% CI, 0.79-0.81) for severe AKI and AKI-D, respectively; for plasma NGAL, the corresponding AUCs were 0.80 (95% CI, 0.790.81) and 0.86 (95% CI, 0.84-0.8 6). Cutoff concentrations at 95% specificity for urinary NGAL were >580 ng/mL with 27% sensitivity for severe AKI and >589 ng/mL with 24% sensitivity for AKI-D. Corresponding cutoffs for plasma NGAL were >364 ng/mL with 44% sensitivity and >546 ng/mL with 26% sensitivity, respectively.

    Limitations: Practice variability in initiation of dialysis. Imperfect harmonization of data across studies. Conclusions: Urinary and plasma NGAL concentrations may identify patients at high risk for AKI in clinical research and practice. The cutoff concentrations reported in this study require prospective evaluation.

  • 17.
    Aldenbratt, Annika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Lindberg, Christopher
    Johannesson, Elias
    Hammarsten, Ola
    Svensson, Maria K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Estimation of kidney function in patients with primary neuromuscular diseases: is serum cystatin C a better marker of kidney function than creatinine?2022In: JN. Journal of Nephrology, ISSN 1121-8428, E-ISSN 1724-6059, Vol. 35, no 2, p. 493-503Article in journal (Refereed)
    Abstract [en]

    Background: Using serum creatinine leads to an overestimation of kidney function in patients with primary neuromuscular disorders, and reduced kidney function may remain undetected. Cystatin C (CysC) could provide a better estimation.

    Aim: To evaluate the precision, accuracy, and bias of two creatinine-, one cystatin C-based and one combined equation to estimate glomerular filtration rate (eGFR) in patients with primary neuromuscular disease.

    Patients and methods: Of the 418 patients initially identified at the out-patient clinic, data on kidney function was obtained for 145 adult patients (age 46 ± 14 years, BMI 26 ± 6 kg/m2) with primary neuromuscular disease. Kidney function was measured by iohexol clearance, and blood samples for serum creatinine and CysC were drawn simultaneously. Bias was defined as the mean difference between eGFR and measured iohexol clearance, and accuracy as the proportion of eGFRs within ± 10% (P10) of measured clearance.

    Results: Kidney function (iohexol clearance) was 81 ± 19 (38–134) ml/min/1.73m2. All equations overestimated kidney function by 22–60 ml/min/1.73m2. eGFR CysC had the lowest bias overall 22 (95% CI 20–26) ml/min/1.73m2 also at all levels of kidney function we evaluated (at 30–59 ml/min/1.73m2 bias was 27 (95% CI 21–35), at 60–89 it was 25 (95% CI 20–28) and at ≥ 90 it was 12 (95% CI 7–22)). eGFR CysC also had the best accuracy in patients with reduced kidney function (P10 was 5.9% at 30–59 ml/min/1.73m2).

    Conclusions: Cystatin C-based estimations of kidney function performed better than creatinine-based ones in patients with primary neuromuscular disease, but most importantly, all evaluated equations overestimated kidney function, especially in patients with reduced kidney function. Therefore, kidney function should be measured by gold-standard methods when precision and accuracy are needed.

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  • 18.
    Aldenbratt, Annika
    et al.
    Sahlgrens Univ Hosp, Dept Nephrol, Gothenburg, Sweden.
    Lindberg, Christopher
    Sahlgrens Univ Hosp, Dept Neurol, Neuromuscular Ctr, Gothenburg, Sweden.
    Svensson, Maria K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Reduced renal function in patients with Myotonic Dystrophy type 1 and the association to CTG expansion and other potential risk factors for chronic kidney disease2017In: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 27, no 11, p. 1038-1042Article in journal (Refereed)
    Abstract [en]

    Myotonic dystrophy type 1 (DM1) affects several organs. Disease severity and age at onset are correlated to the CTG repeat expansion. The aim of this study was to assess renal function and the association to numbers of CTG repeat expansion in patients with DM1. Ninety-eight patients with DM1 were included. Glomerular filtration rate (measured GFR) was measured using iohexol clearance. Data on CTG repeats were available in 83/98 (85%) patients. The overall mGFR was 74 (16) ml/min/1.73 m(2) (range 38-134). Sixty-four patients (69%) had a mild and sixteen patients (17%) a moderate decrease in renal function (mGFR 60-89 and 30-59 ml/min/1.73 m(2), respectively). No correlations were found between CTG repeats and mGFR (r = 0.10, p = 0.4) or between CTG repeats and serum cystatin C (r = 0.12, p = 0.29). CTG repeats was positively correlated to creatinine-based estimates of GFR (eGFR) (modified diet in renal disease r = 0.49, p < 0.001, CKD-EPI creatinine equation; r = 0.50, p < 0.001), but analyses using Structural Equation Modeling showed no correlation. The correlation was explained by an indirect effect via serum creatinine and skeletal muscle mass index. In conclusion, patients with DM1 seem to have a slight decrease in renal function but there is no association between renal function and the number of CTG repeats, a marker of disease severity.

  • 19.
    Alderson, Helen V
    et al.
    Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Salford Royal NHS Foundation Trust, Salford, UK.
    Chinnadurai, Rajkumar
    Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Salford Royal NHS Foundation Trust, Salford, UK..
    Ibrahim, Sara T
    Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Salford Royal NHS Foundation Trust, Salford, UK..
    Asar, Ozgur
    Department of Biostatistics and Medical Informatics, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey..
    Ritchie, James P
    Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Salford Royal NHS Foundation Trust, Salford, UK..
    Middleton, Rachel
    Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Salford Royal NHS Foundation Trust, Salford, UK..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Diggle, Peter J
    CHICAS, Lancaster Medical School, Lancaster University, Lancaster, UK..
    Larsson, Tobias E
    Department of Clinical Science, Intervention and Technology, Renal Unit, Karolinska Institute, Stockholm, Sweden..
    Kalra, Philip A
    Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Salford Royal NHS Foundation Trust, Salford, UK..
    Longitudinal change in c-terminal fibroblast growth factor 23 and outcomes in patients with advanced chronic kidney disease2021In: BMC Nephrology, E-ISSN 1471-2369, Vol. 22, no 1, article id 329Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Fibroblast growth factor23 (FGF23) is elevated in CKD and has been associated with outcomes such as death, cardiovascular (CV) events and progression to Renal Replacement therapy (RRT). The majority of studies have been unable to account for change in FGF23 over time and those which have demonstrate conflicting results. We performed a survival analysis looking at change in c-terminal FGF23 (cFGF23) over time to assess the relative contribution of cFGF23 to these outcomes.

    METHODS: We measured cFGF23 on plasma samples from 388 patients with CKD 3-5 who had serial measurements of cFGF23, with a mean of 4.2 samples per individual. We used linear regression analysis to assess the annual rate of change in cFGF23 and assessed the relationship between time-varying cFGF23 and the outcomes in a cox-regression analysis.

    RESULTS: Across our population, median baseline eGFR was 32.3mls/min/1.73m2, median baseline cFGF23 was 162 relative units/ml (RU/ml) (IQR 101-244 RU/mL). Over 70 months (IQR 53-97) median follow-up, 76 (19.6%) patients progressed to RRT, 86 (22.2%) died, and 52 (13.4%) suffered a major non-fatal CV event. On multivariate analysis, longitudinal change in cFGF23 was significantly associated with risk for death and progression to RRT but not non-fatal cardiovascular events.

    CONCLUSION: In our study, increasing cFGF23 was significantly associated with risk for death and RRT.

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  • 20.
    Alderson, Helen V.
    et al.
    Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK;Salford Royal NHS Foundation Trust, Salford, UK..
    Ritchie, James P
    Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK;Salford Royal NHS Foundation Trust, Salford, UK..
    Middleton, Rachel
    Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK;Salford Royal NHS Foundation Trust, Salford, UK..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Larsson, Tobias E
    Department of Clinical Science, Intervention and Technology, Renal Unit, Karolinska Institute, Stockholm, Sweden..
    Kalra, Philip A
    Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK;Salford Royal NHS Foundation Trust, Salford, UK..
    FGF-23 and Osteoprotegerin but not Fetuin-A are associated with death and enhance risk prediction in non-dialysis chronic kidney disease stages 3-52016In: Nephrology (Carlton. Print), ISSN 1320-5358, E-ISSN 1440-1797, Vol. 21, no 7, p. 566-573Article in journal (Refereed)
    Abstract [en]

    AIM: Numerous biomarkers have been shown to associate with clinical endpoints in chronic kidney disease (CKD). There is limited evidence whether biomarkers improve risk prediction in relation to clinical outcomes. Our study investigates whether a small suite of key chronic kidney disease-mineral and bone disorder biomarkers could be used to enhance risk assessment in CKD.

    METHODS: Fetuin-A, fibroblast growth factor-23 and osteoprotegerin were measured on baseline plasma samples from 463 patients recruited to the Chronic Renal Insufficiency Standards Implementation Study. The biomarkers were analysed in relation to progression to end stage kidney disease, death and major cardiovascular events.

    RESULTS: Over a median follow up of 46 months (interquartile range 21-69), fibroblast growth factor-23 was associated with risk for renal replacement therapy (hazard ratio (HR) 1.35, P = 0.05, 95% confidence interval (CI) 1.001-1.820), cardiovascular events (HR 1.74 P < 0.001, 95% CI 1.303-1.305) and death (HR 1.4 P = 0.005, 95% CI 1.109-1.767). Osteoprotegerin was associated with risk for death (HR 1.06, P = 0.03, 95% CI 1.006-1.117). There was no clear association between Fetuin-A and any of the clinical endpoints. The addition of biomarkers to risk models led to marginal improvement in model discrimination and reclassification.

    CONCLUSION: Biomarkers are often associated with clinical endpoints, and we observed such associations in our study of patients with advanced CKD. However, the markers analysed in our study were of limited benefit in improving the prediction of these outcomes. Any extra information biomarkers may provide to improve risk prediction in clinical practice needs to be carefully balanced against the potential cost of these tools.

  • 21.
    Alehagen, Urban
    et al.
    Division of Cardiovascular Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, SE-581 85 Linköping, Sweden.
    Aaseth, Jan
    Research Department, Innlandet Hospital Trust, N-2381 Brumunddal, Norway.
    Alexander, Jan
    Norwegian Institute of Public Health, N-0403 Oslo, Norway.
    Brismar, Kerstin
    Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, SE-17176 Stockholm, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Selenium and Coenzyme Q10 Supplementation Improves Renal Function in Elderly Deficient in Selenium: Observational Results and Results from a Subgroup Analysis of a Prospective Randomised Double-Blind Placebo-Controlled Trial2020In: Nutrients, E-ISSN 2072-6643, Vol. 12, no 12, article id 3780Article in journal (Refereed)
    Abstract [en]

    A low selenium intake is found in European countries, and is associated with increased cardiovascular mortality. There is an association between selenium level and the severity of kidney disease. An association between inflammation and selenium intake is also reported. The coenzyme Q10 level is decreased in kidney disease. The aim of this study was to examine a possible association between selenium and renal function in an elderly population low in selenium and coenzyme Q10, and the impact of intervention with selenium and coenzyme Q10 on the renal function. The association between selenium status and creatinine was studied in 589 elderly persons. In 215 of these (mean age 71 years) a randomised double-blind placebo-controlled prospective trial with selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) (n = 117) or placebo (n = 98) was conducted. Renal function was determined using measures of glomerular function at the start and after 48 months. The follow-up time was 5.1 years. All individuals were low on selenium (mean 67 μg/L (SD 16.8)). The changes in renal function were evaluated by measurement of creatinine, cystatin-C, and the use of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) algorithm, and by the use of T-tests, repeated measures of variance and ANCOVA analyses. An association between low selenium status and impaired renal function was observed. Intervention causes a significantly lower serum creatinine, and cystatin-C concentration in the active treatment group compared with those on placebo (p = 0.0002 and p = 0.001 resp.). The evaluation with CKD-EPI based on both creatinine and cystatin-C showed a corresponding significant difference (p < 0.0001). All validations showed corresponding significant differences. In individuals with a deficiency of selenium and coenzyme Q10, low selenium status is related to impaired renal function, and thus supplementation with selenium and coenzyme Q10 results in significantly improved renal function as seen from creatinine and cystatin-C and through the CKD-EPI algorithm. The explanation could be related to positive effects on inflammation and oxidative stress as a result of the supplementation.

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  • 22. Ali, Muhammad
    et al.
    Acosta Ruiz, Vanessa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Psutka, Sarah P.
    Liu, David
    Siva, Shankar
    Ablative Therapies for Localized Primary Renal Cell Carcinoma2022In: Société Internationale d’Urologie Journal, ISSN 2563-6499, Vol. 3, no 6, p. 437-449Article in journal (Refereed)
    Abstract [en]

    Surgery with either partial or radical nephrectomy remains the standard of care for localized primary renal cellcarcinoma (RCC). However, most RCCs are detected in an older age group, and some may have multiple comorbiditiesthat preclude surgery. Thermal ablation (TA) with radiofrequency ablation (RFA), cryoablation (CA), or microwaveablation (MWA) is considered an alternative to extirpative surgical procedures for select patients with small renaltumors. There is more than 90% post-ablation local control in carefully selected patients with reported complicationrates of less than 10%. Most thermal ablation require only a single procedure. More recently, stereotactic ablativebody radiotherapy (SABR) has emerged as an attractive noninvasive treatment modality for elderly patients withcomorbidities and localized RCC. It has shown more than 90% local control rates for both small and relatively largertumors (> 4 cm). Modest post-SABR renal function decline has been observed. Despite most patients presenting withmild or moderate chronic kidney disease there is less than a 5% chance of progression to end-stage renal disease. Thisarticle aims to summarize the key evidence and ablative treatment’s optimal patient selection, efficacy, and toxicity.

  • 23. Aljabery, Firas
    et al.
    Liedberg, Fredrik
    Häggström, Christel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Department of Biobank Research, Umeå University; Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University.
    Ströck, Viveka
    Hosseini, Abolfazl
    Gårdmark, Truls
    Sherif, Amir
    Jerlström, Tomas
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Hagberg, Oskar
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Treatment and prognosis of patients with urinary bladder cancer with other primary cancers: a nationwide population-based study in the Bladder Cancer Data Base Sweden (BladderBaSe).2020In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 126, no 5, p. 625-632Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To study how patients with urinary bladder cancer (UBC) with previous or concomitant other primary cancers (OPCs) were treated, and to investigate their prognosis.

    PATIENTS AND METHODS: Using nationwide population-based data in the Bladder Cancer Data Base Sweden (BladderBaSe), we analysed the probability of treatment with curative intent, and UBC-specific and overall survival (OS) in patients with UBC diagnosed in the period 1997-2014 with or without OPC. The analyses considered the patient's characteristics, UBC tumour stage at diagnosis, and site of OPC.

    RESULTS: There were 38 689 patients, of which 9804 (25%) had OPCs. Those with synchronous OPCs more often had T2 and T3 tumours and clinically distant disease at diagnosis than those with UBC only. Patients with synchronous prostate cancer, female genital cancer and lower gastro-intestinal cancer were more often treated with curative intent than patients with UBC only. When models of survival were adjusted for age at diagnosis, marital status, education, year of diagnosis, Charlson Comorbidity Index and T-stage, UBC-specific survival was similar to patients with UBC only, but OS was lower for patients with synchronous OPC, explained mainly by deaths in OPC primaries with a bad prognosis.

    CONCLUSIONS: OPC is common in patients with UBC. Treatment for UBC, after or in conjunction with an OPC, should not be neglected and carries just as high a probability of success as treatment in patients with UBC only. The needs of patients with UBC and OPC, and optimisation of their treatment considering their complicated disease trajectory are important areas of research.

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  • 24.
    Al-Mashhadi, Ammar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery.
    Häggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Läckgren, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery.
    Ladjevardi, Sam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Nevéus, Tryggve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Stenberg, Arne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery.
    Persson, A. Erik G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlstrom, Mattias
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Changes of arterial pressure following relief of obstruction in adults with hydronephrosis2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 4, p. 216-224Article in journal (Refereed)
    Abstract [en]

    Background: As much as 20% of all cases of hypertension are associated with kidney malfunctions. We have previously demonstrated in animals and in pediatric patients that hydronephrosis causes hypertension, which was attenuated by surgical relief of the ureteropelvic junction (UPJ) obstruction. This retrospective cohort study aimed to investigate: (1) the proposed link between hydronephrosis, due to UPJ obstruction, and elevated arterial pressure in adults; and (2) if elevated blood pressure in patients with hydronephrosis might be another indication for surgery.

    Materials and methods: Medical records of 212 patients undergoing surgical management of hydronephrosis, due to UPJ obstruction, between 2000 and 2016 were assessed. After excluding patients with confounding conditions and treatments, paired arterial pressures (i.e. before/after surgery) were compared in 49 patients (35 years old; 95% CI 29–39). Split renal function was evaluated by using mercaptoacetyltriglycine (MAG3) renography before surgical management of the hydronephrotic kidney.

    Results: Systolic (−11 mmHg; 95% CI 6–15 mmHg), diastolic (−8 mmHg; 95% CI 4–11 mmHg), and mean arterial (-9 mmHg; 95% CI 6–12) pressures were significantly reduced after relief of the obstruction (p < 0.001). Split renal function of the hydronephrotic kidney was 39% (95% CI 37–41). No correlations were found between MAG3 and blood pressure level before surgery or between MAG3 and the reduction of blood pressure after surgical management of the UPJ obstruction.

    Conclusions: In adults with hydronephrosis, blood pressure was reduced following relief of the obstruction. Our findings suggest that elevated arterial pressure should be taken into account as an indication to surgically correct hydronephrosis.

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  • 25.
    Al-Mashhadi, Ammar Nadhom Farman
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Checa, Antonio
    Karolinska Institute.
    Wåhlin, Nils
    Karolinska Institute.
    Nevéus, Tryggve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Fossum, Magdalena
    Karolinska institute.
    Wheelock, Craig E.
    Karolinska Institute.
    Karanikas, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Stenberg, Arne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Persson, A. Erik G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlström, Mattias
    Karolinska Institute.
    Changes in arterial pressure and markers of nitric oxide homeostasis and oxidative stress following surgical correction of hydronephrosis in children2018In: Pediatric nephrology (Berlin, West), ISSN 0931-041X, E-ISSN 1432-198X, Vol. 33, no 4, p. 639-649Article in journal (Refereed)
    Abstract [en]

    Objective Recent clinical studies have suggested an increased risk of elevated arterial pressure in patients with hydronephrosis. Animals with experimentally induced hydronephrosis develop hypertension, which is correlated to the degree of obstruction and increased oxidative stress. In this prospective study we investigated changes in arterial pressure, oxidative stress, and nitric oxide (NO) homeostasis following correction of hydronephrosis.

    Methods Ambulatory arterial pressure (24 h) was monitored in pediatric patients with hydronephrosis (n = 15) before and after surgical correction, and the measurements were compared with arterial pressure measurements in two control groups, i.e. healthy controls (n = 8) and operated controls (n = 8). Markers of oxidative stress and NO homeostasis were analyzed in matched urine and plasma samples.

    Results The preoperative mean arterial pressure was significantly higher in hydronephrotic patients [83 mmHg; 95% confidence interval (CI) 80–88 mmHg] than in healthy controls (74 mmHg; 95% CI 68–80 mmHg; p < 0.05), and surgical correction of ureteral obstruction reduced arterial pressure (76 mmHg; 95% CI 74–79 mmHg; p < 0.05). Markers of oxidative stress (i.e., 11- dehydroTXB2, PGF2α, 8-iso-PGF2α, 8,12-iso-iPF2α-VI) were significantly increased (p < 0.05) in patients with hydronephrosis compared with both control groups, and these were reduced following surgery (p < 0.05). Interestingly, there was a trend for increased NO synthase activity and signaling in hydronephrosis, which may indicate compensatory mechanism(s).

    Conclusion This study demonstrates increased arterial pressure and oxidative stress in children with hydronephrosis compared with healthy controls, which can be restored to normal levels by surgical correction of the obstruction. Once reference data on ambulatory blood pressure in this young age group become available, we hope cut-off values can be defined for deciding whether or not to correct hydronephrosis surgically.

    Keywords Blood pressure . Hydronephrosis . Hypertension . Nitric oxide . Oxidative stress . Ureteral obstruction 

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  • 26.
    Al-Mashhadi, Ammar Nadhom Farman
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Nevéus, Tryggve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Stenberg, Arne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Karanikas, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Persson, A. Erik G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlstrom, Mattias
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Wahlin, Nils
    Department of Pediatric Surgery, Astrid Lindgren Hospital, Karolinska Institutet, Stockholm, Sweden.
    Surgical treatment reduces blood pressure in children with unilateral congenital hydronephrosis2015In: Journal of Pediatric Urology, ISSN 1477-5131, E-ISSN 1873-4898, Vol. 11, no 2, p. 91.e1-91.e6Article in journal (Refereed)
    Abstract [en]

    Objective Renal disorders can cause hypertension, but less is known about the influence of hydronephrosis on blood pressure. Hydronephrosis due to pelvo-ureteric junction obstruction (PUJO) is a fairly common condition (incidence in newborns of 0.5-1%). Although hypertensive effects of hydronephrosis have been suggested, this has not been substantiated by prospective studies in humans [1-3]. Experimental studies with PUJO have shown that animals with induced hydronephrosis develop salt-sensitive hypertension, which strongly correlate to the degree of obstruction [4-7]. Moreover, relief of the obstruction normalized blood pressure [8]. In this first prospective study our aim was to study the blood pressure pattern in pediatric patients with hydronephrosis before and after surgical correction of the ureteral obstruction. Specifically, we investigated if preoperative blood pressure is reduced after surgery and if split renal function and renographic excretion curves provide any prognostic information. Patients and methods Twelve patients with unilateral congenital hydronephrosis were included in this prospective study. Ambulatory blood pressure (24 h) was measured preoperatively and six months after surgery. Preoperative evaluations of bilateral renal function by Tc99m-MAG3 scintigraphy, and renography curves, classified according to O'Reilly, were also performed. Results As shown in the summary figure, postoperative systolic (103 +/- 2 mmHg) and diastolic (62 +/- 2 mmHg) blood pressure were significantly lower than those obtained preoperatively (110 +/- 4 and 69 +/- 2 mmHg, respectively), whereas no changes in circadian variation or pulse pressure were observed. Renal functional share of the hydronephrotic kidney ranged from 11 to 55%. There was no correlation between the degree of renal function impairment and the preoperative excretory pattern, or between the preoperative excretory pattern and the blood pressure reduction postoperatively. However, preoperative MAG3 function of the affected kidney correlated with the magnitude of blood pressure change after surgery. Discussion Correction of the obstruction lowered blood pressure, and the reduction in blood pressure appeared to correlate with the degree of renal functional impairment, but not with the excretory pattern. Thus, in the setting of hypertension, it appears that the functional share of the hydronephrotic kidney should be considered an indicator of the need for surgery, whereas the renography curve is less reliable. The strength of the present study is the prospective nature and that ambulatory blood pressure monitoring was used. Future longitudinal prolonged follow-up studies are warranted to confirm the present findings, and to understand if a real nephrogenic hypertension with potential necessity of treatment will develop. Conclusion This novel prospective study in patients with congenital hydronephrosis demonstrates a reduction in blood pressure following relief of the obstruction. Based on the present results, we propose that the blood pressure level should also be taken into account when deciding whether to correct hydronephrosis surgically or not.

  • 27.
    Almdalal, Tarik
    et al.
    Eskilstuna Country Hosp, Dept Surg & Urol, Eskilstuna, Sweden..
    Sundqvist, Pernilla
    Örebro Univ, Fac Med & Hlth, Dept Urol, Örebro, Sweden..
    Harmenberg, Ulrika
    Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden..
    Hellström, Mikael
    Department of Radiology, Sahlgrenska Academy/Sahlgrenska University Hospital, Gothenburg University, Gothenburg, Sweden..
    Lindskog, magli409
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Lindblad, Per
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden..
    Lundstam, Svan
    Department of Urology and Oncology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden..
    Ljungberg, Börje
    Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden..
    Clinical T1a Renal Cell Carcinoma, Not Always a Harmless Disease—A National Register Study2022In: European Urology Open Science, ISSN 2666-1691, E-ISSN 2666-1683, Vol. 39, p. 22-28Article in journal (Refereed)
    Abstract [en]

    Background: T1a renal cell carcinoma (RCC) is typically considered a curable disease, irrespective of the choice of local treatment modality.

    Objective: To identify factors associated with the risk of local and distant recurrence, and overall survival (OS) in patients with primary nonmetastatic clinical T1a RCC.

    Design setting and participants: A population-based nationwide register study of all 1935 patients with cT1a RCC, diagnosed during 2005-2012, identified through The National Swedish Kidney Cancer Register, was conducted.

    Outcome measurements and statistical analysis: Outcome variables were recurrence (local or distant) and OS. Possible explanatory variables included tumor size, RCC type, T stage, surgical technique, age, and gender. Associations with disease recurrence and OS were evaluated by multivariable regression and Cox multivariate analyses, respectively.

    Results and limitations: Among 1935 patients, 938 were treated with radical nephrectomy, 738 with partial nephrectomy, and 169 with ablative treatments, while 90 patients had no surgery. Seventy-eight (4%) patients were upstaged to pT3. Local or metastatic recurrences occurred in 145 (7.5%) patients, significantly more often after ablation (17.8%). The risk of recurrence was associated with tumor size, upstaging, and ablation. Larger tumor size, disease recurrence, and older age adversely affected OS, whereas partial nephrectomy and chromophobe RCC (chRCC) were associated with improved survival. Limitations include register design and a lack of comorbidity or performance status data.

    Conclusions: Upstaging and recurrence occurred, respectively, in 4.0% and 7.5% of patients with nonmetastatic RCCs ≤4 cm. Tumor size upstaging and ablation were associated with the risk for recurrence, while tumor size and recurrence were associated with decreased OS. Patients with chRCC and partial nephrectomy had prolonged OS in a real-world setting.

    Patient summary: We studied factors that may influence the risk of disease recurrence and overall survival, in a large nationwide patient cohort having nonmetastatic renal cell carcinoma ≤4 cm. Tumor size, tumor type, and treatment were associated with the risk of recurrence and overall death. Partial nephrectomy prolonged overall survival.

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  • 28.
    Alvaeus, Julia
    et al.
    Umeå Univ, Dept Surg & Perioperat Sci, Urol & Androl, S-90185 Umeå, Sweden..
    Rosenblatt, Robert
    Umeå Univ, Dept Surg & Perioperat Sci, Urol & Androl, S-90185 Umeå, Sweden.;Stockholm South Gen Hosp, Dept Urology, Karolinska Inst, Stockholm, Sweden..
    Johansson, Markus
    Umeå Univ, Dept Surg & Perioperat Sci, Urol & Androl, S-90185 Umeå, Sweden.;Sundsvall Hosp, Dept Urol, Sundsvall, Sweden..
    Alamdari, Farhood
    Vastmanland Hosp, Dept Urol, Västerås, Sweden..
    Jakubczyk, Tomasz
    Lanssjukhuset Ryhov, Dept Urol, Jönköping, Sweden..
    Holmström, Benny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Hemdan, Tammer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Huge, Ylva
    Linköping Univ, Dept Clin & Expt Med, Div Urol, Linköping, Sweden..
    Aljabery, Firas
    Linköping Univ, Dept Clin & Expt Med, Div Urol, Linköping, Sweden..
    Gabrielsson, Susanne
    Karolinska Inst, Dept Med Solna, Div Immunol & Allergy, Stockholm, Sweden..
    Riklund, Katrine
    Umeå Univ, Dept Radiat Sci, Umeå, Sweden..
    Winqvist, Ola
    Karolinska Univ Hosp, Dept Clin Immunol, Stockholm, Sweden..
    Sherif, Amir
    Umeå Univ, Dept Surg & Perioperat Sci, Urol & Androl, S-90185 Umeå, Sweden..
    Fewer tumour draining sentinel nodes in patients with progressing muscle invasive bladder cancer, after neoadjuvant chemotherapy and radical cystectomy2020In: World journal of urology, ISSN 0724-4983, E-ISSN 1433-8726, Vol. 38, no 9, p. 2207-2213Article in journal (Refereed)
    Abstract [en]

    Purpose

    To examine the relationship between the number of tumour draining sentinel nodes (SNs) and pathoanatomical outcomes, in muscle-invasive bladder cancer (MIBC), in patients undergoing neoadjuvant chemotherapy (NAC) and radical cystectomy (RC).

    Materials and Methods

    In an ongoing prospective multicenter study, we included 230 patients with suspected urothelial MIBC from ten Swedish urological centers. All underwent TURb and clinical staging. From the cohort, 116 patients with urothelial MIBC; cT2-cT4aN0M0, underwent radical cystectomy (RC) and lymphadenectomy with SN-detection (SNd). 83 patients received cisplatin-based NAC and 33 were NAC-naïve. The number and locations of detected SNs and non-SNs were recorded for each patient. The NAC treated patients were categorized by pathoanatomical outcomes post-RC into three groups: complete responders (CR), stable disease (SD) and progressive disease (PD). Selected covariates with possible impact on SN-yield were tested in uni -and multivariate analyses for NAC-treated patients only.

    Results

    In NAC treated patients, the mean number of SNs was significantly higher in CR patients (3.3) and SD patients (3.6) compared with PD patients (1.4) (p = 0.034). In a linear multivariate regression model, the number of harvested nodes was the only independent variable that affected the number of SNs (p = 0.0004).

    Conclusions

    The number of tumor-draining SNs in NAC-treated patients was significantly lower in patients with progressive disease.

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  • 29.
    Alverbratt, Charlotte
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Oncol, S-41396 Gothenburg, Sweden.
    Vikman, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Eriksson, Marie Hjalm
    St Goran Hosp, Dept Surg, Stockholm, Sweden.;Karolinska Inst, Dept Oncol & Pathol, Stockholm, Sweden.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Lissbrant, Ingela Franck
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Oncol, S-41396 Gothenburg, Sweden.
    Time difference in retrieving clinical information in Patient-overview Prostate Cancer compared to electronic health records2022In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 56, no 2, p. 95-101Article in journal (Refereed)
    Abstract [en]

    Background Patients with advanced prostate cancer (PCa) typically undergo numerous lines of treatment leading to large amounts of information in Electronic Health Records (EHRs). The Patient-overview Prostate Cancer (PPC) presents clinical information in a graphical overview. The aim of this study was to measure time spent on retrieving clinical information in PPC compared to EHRs, to assess if retrieved data was correct and to explore usability of PPC.

    Material and methods Oncologists, urologists and nurses in three hospitals in Sweden were timed when filling out questionnaires about patients using PPC and two different EHRs; Melior and COSMIC. Time and number of errors were analysed using linear mixed models (LMMs). Usability of PPC was measured with the System Usability Scale.

    Results The LMM showed a significantly shorter time to retrieve information in PPC compared to EHRs. The estimated time to complete one questionnaire was 8 minutes (95% CI = 6-10, p < 0.001) in PPC compared to 25 minutes in Melior and 21 minutes in COSMIC. Compared to PPC, the estimated time difference was 17 minutes longer in Melior (95% CI = 14-20, p < 0.001) and 13 minutes longer in COSMIC (95% CI = 10-17, p < 0.001). The LMM showed significantly fewer errors in PPC compared to Melior. No significant difference in the number of errors was found between PPC and COSMIC. The usability of PPC was rated as excellent by oncologists, urologists and nurses.

    Conclusion A graphical overview of a patient's medical history, as in PPC, gives health staff rapid access to relevant information with a high degree of usability.

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  • 30.
    Amin, Risul
    et al.
    Karolinska Inst, Novum, Clin Res Ctr, Expt Canc Med, S-14186 Stockholm, Sweden.
    He, Rui
    Karolinska Inst, Novum, Clin Res Ctr, Expt Canc Med, S-14186 Stockholm, Sweden.
    Gupta, Dhanu
    Karolinska Univ Hosp, Novum, Clin Res Ctr, Huddinge, Sweden.
    Zheng, Wenyi
    Karolinska Inst, Novum, Clin Res Ctr, Expt Canc Med, S-14186 Stockholm, Sweden.
    Burmakin, Mikhail
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Mohammad, Dara K.
    Karolinska Inst, Novum, Clin Res Ctr, Expt Canc Med, S-14186 Stockholm, Sweden;Salahaddin Univ Erbil, Coll Agr Engn Sci, Erbil 44002, Kurdistan Regio, Iraq.
    DePierre, Joseph W.
    Stockholm Univ, Arrhenius Labs Nat Sci, Dept Biochem & Biophys, SE-10691 Stockholm, Sweden.
    Sadeghi, Behnam
    Karolinska Inst, Dept CLINTEC, Translat Cell Therapy Res TCR, Stockholm, Sweden.
    Olauson, Hannes
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med, Huddinge, Sweden;Karolinska Univ Hosp, Huddinge, Sweden.
    Wernerson, Annika
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med, Huddinge, Sweden;Karolinska Univ Hosp, Huddinge, Sweden;Karolinska Univ Hosp, Clin Pathol & Cytol, Huddinge, Sweden.
    El-Andaloussi, Samir
    Karolinska Univ Hosp, Novum, Clin Res Ctr, Huddinge, Sweden.
    Hassan, Moustapha
    Karolinska Inst, Novum, Clin Res Ctr, Expt Canc Med, S-14186 Stockholm, Sweden;Karolinska Univ Hosp, Clin Res Ctr KFC, Huddinge, Sweden.
    Abedi-Valugerdi, Manuchehr
    Karolinska Inst, Novum, Clin Res Ctr, Expt Canc Med, S-14186 Stockholm, Sweden.
    The kidney injury caused by the onset of acute graft-versus-host disease is associated with down-regulation of αKlotho2020In: International Immunopharmacology, ISSN 1567-5769, E-ISSN 1878-1705, Vol. 78, article id 106042Article in journal (Refereed)
    Abstract [en]

    Acute graft-versus-host disease (aGVHD) and kidney injury are the major complications after allogeneic hematopoietic stem cell transplantation (HSCT). Although the underlying mechanisms for the development of these complications are not yet fully understood, it has been proposed that emergence of aGVHD contributes to the development of kidney injury after HSCT. We have shown previously that aGVHD targets the kidney in a biphasic manner: at the onset, inflammatory genes are up-regulated, while when aGVHD becomes established, donor lymphocytes infiltrate the kidney. Here, we characterize renal manifestations at the onset of aGVHD. Mice receiving allogeneic bone marrow and spleen cells displayed symptoms of aGVHD and elevated serum levels of tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) within 4 days. There was concurrent kidney injury with the following characteristics: (1) elevated expression of the kidney injury biomarker, neutrophil gelatinase-associated lipocalin (NGAL), (2) accumulation of hetero-lysosomes in proximal tubule epithelial cells, and (3) reductions in αKlotho mRNA and protein and increased serum levels of fibroblast growth factor 23 (Fgf23), phosphate and urea. This situation resembled acute renal injury caused by bacterial lipopolysaccharide. We conclude that the onset of aGVHD is associated with kidney injury involving down-regulation of αKlotho, a sight that may inspire novel therapeutic approaches.

  • 31.
    Anderberg, Sara B.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Luther, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Physiological aspects of Toll-like receptor 4 activation in sepsis-induced acute kidney injury2017In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 219, no 3, p. 575-590Article, review/survey (Refereed)
    Abstract [en]

    Sepsis-induced acute kidney injury (SI-AKI) is common and associated with high mortality. Survivors are at increased risk of chronic kidney disease. The precise mechanism underlying SI-AKI is unknown, and no curative treatment exists. Toll-like receptor 4 (TLR4) activates the innate immune system in response to exogenous microbial products. The result is an inflammatory reaction aimed at clearing a potential infection. However, the consequence may also be organ dysfunction as the immune response can cause collateral damage to host tissue. The purpose of this review is to describe the basis for how ligand binding to TLR4 has the potential to cause renal dysfunction and the mechanisms by which this may take place in gram-negative sepsis. In addition, we highlight areas for future research that can further our knowledge of the pathogenesis of SI-AKI in relation to TLR4 activation. TLR4 is expressed in the kidney. Activation of TLR4 causes cytokine and chemokine release as well as renal leucocyte infiltration. It also results in endothelial and tubular dysfunction in addition to altered renal metabolism and circulation. From a physiological standpoint, inhibiting TLR4 in large animal experimental SI-AKI significantly improves renal function. Thus, current evidence indicates that TLR4 has the ability to mediate SI-AKI by a number of mechanisms. The strong experimental evidence supporting a role of TLR4 in the pathogenesis of SI-AKI in combination with the availability of pharmacological tools to target TLR4 warrants future human studies.

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  • 32. Andersson, Gustav
    et al.
    Wennersten, Christoffer
    Gaber, Alexander
    Boman, Karolina
    Nodin, Bjorn
    Uhlen, Mathias
    Segersten, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Jirstrom, Karin
    Reduced expression of ezrin in urothelial bladder cancer signifies more advanced tumours and an impaired survival: validatory study of two independent patient cohorts2014In: BMC Urology, E-ISSN 1471-2490, Vol. 14, p. 36-Article in journal (Refereed)
    Abstract [en]

    Background: Reduced membranous expression of the cytoskeleton-associated protein ezrin has previously been demonstrated to correlate with tumour progression and poor prognosis in patients with T1G3 urothelial cell carcinoma of the bladder treated with non-maintenance Bacillus Calmette-Guerin (n = 92), and the associations with adverse clinicopathological factors have been validated in another, unselected, cohort (n = 104). In the present study, we examined the prognostic significance of ezrin expression in urothelial bladder cancer in a total number of 442 tumours from two independent patient cohorts. Methods: Immunohistochemical expression of ezrin was evaluated in tissue microarrays with tumours from one retrospective cohort of bladder cancer (n = 110; cohort I) and one population-based cohort (n = 342; cohort II). Classification regression tree analysis was applied for selection of prognostic cutoff. Kaplan-Meier analysis, log rank test and Cox regression proportional hazards' modeling were used to evaluate the impact of ezrin on 5-year overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS). Results: Ezrin expression could be evaluated in tumours from 100 and 342 cases, respectively. In both cohorts, reduced membranous ezrin expression was significantly associated with more advanced T-stage (p < 0.001), high grade tumours (p < 0.001), female sex (p = 0.040 and p = 0.013), and membranous expression of podocalyxin-like protein (p < 0.001 and p = 0.009). Moreover, reduced ezrin expression was associated with a significantly reduced 5-year OS in both cohorts (HR = 3.09 95% CI 1.71-5.58 and HR = 2.15(1.51-3.06), and with DSS in cohort II (HR = 2.77, 95% CI 1.78-4.31). This association also remained significant in adjusted analysis in Cohort I (HR1.99, 95% CI 1.05-3.77) but not in Cohort II. In pTa and pT1 tumours in cohort II, there was no significant association between ezrin expression and time to progression. Conclusions: The results from this study validate previous findings of reduced membranous ezrin expression in urothelial bladder cancer being associated with unfavourable clinicopathological characteristics and an impaired survival. The utility of ezrin as a prognostic biomarker in transurethral resection specimens merits further investigation.

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  • 33.
    Andersson, Marie
    et al.
    Helsingborg Hosp, Dept Urol, Charlotte Yhlensgata 10, S-25187 Helsingborg, Sweden..
    Berger, Marthe
    Lillebelt Hosp, Dept Urol, Vejle, Denmark..
    Zieger, Karsten
    Lillebelt Hosp, Dept Urol, Vejle, Denmark..
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Bläckberg, Mats
    Helsingborg Hosp, Dept Urol, Charlotte Yhlensgata 10, S-25187 Helsingborg, Sweden..
    The diagnostic challenge of suspicious or positive malignant urine cytology findings when cystoscopy findings are normal: an outpatient blue-light flexible cystoscopy may solve the problem2021In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 55, no 4, p. 263-267Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate whether outpatient blue-light flexible cystoscopy could solve the diagnostic challenge of positive or suspicious urine cytology findings despite normal white-light flexible cystoscopy results and normal findings on computerized tomography urography, in patients investigated for urothelial cancer.

    Material and methods: In a multicentre study, a total of 70 examinations were performed with the use of blue-light flexible cystoscopy (photodynamic diagnosis) after intravesical instillation of the fluorescence agent hexaminolevulinate. The examination started with a conventional white-light flexible cystoscopy and then the settings were switched to use blue light. Suspicious lesions were biopsied. Afterwards, the patients were interviewed regarding their experience of the examinations.

    Results: Bladder cancer was diagnosed in 29 out of 70 (41%) cases, among them 14/29 (48%) had malignant lesions seen only in blue light. The majority had carcinoma in situ (21/29). Normal findings were seen in 41 cases that underwent BLFC. During the further course, malignancy of the bladder was detected in six cases (9%) and malignancy of the upper urinary tract was detected in one case (1%). The majority of patients (93%) preferred the blue-light flexible cystoscopy performed at the outpatient clinic instead of the transurethral resection under general anaesthesia.

    Conclusion: Blue-light flexible cystoscopy at the outpatient clinic may be a useful tool to solve unclear cases of a malignant or suspicious urinary cytology suggestive of bladder cancer. The procedure was well tolerated by the patients.

  • 34. Andersson, S O
    et al.
    Rashidkhani, B
    Karlberg, L
    Wolk, A
    Johansson, J E
    Prevalence of lower urinary tract symptoms in men aged 45-79 years: a population-based study of 40,000 Swedish men2004In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 94, no 3, p. 327-331Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To estimate the age-specific prevalence and severity of lower urinary tract symptoms (LUTS) among Swedish men, the intercorrelations between different symptoms, and to assess quality of life and health-seeking behaviour among men with LUTS. SUBJECTS AND METHODS In 1997, an International Prostate Symptom Score (IPSS) questionnaire, together with other questions about lifestyle, was mailed to all men aged 45-79 years living in two counties in Sweden; the analyses included 39 928 men. RESULTS Overall, 18.5% and 4.8% of the men were moderately and severely symptomatic; the prevalence of at least one symptom was 83%. LUTS were strongly age-dependent, with 1.8% of severe symptoms among men aged 45-49 years and increasing to 9.7% among those 75-79 years old. Frequent urination was the most common symptom among men aged <70 years and nocturia among those aged >70 years. Symptoms like hesitancy, poor flow and intermittency were highly correlated with each other (Spearman coefficients 0.56-0.60). There was a high correlation between the IPSS and a poor score for quality of life resulting from the bothersomeness of LUTS (r = 0.70). Among symptomatic subjects, 36% reported a poor quality of life (fairly bad, very bad or terrible). Only 29% of symptomatic subjects (IPSS >7) reported that they had been diagnosed previously for their urinary problems, and only 11% received medication for that. CONCLUSION Although the prevalence of LUTS in Sweden is high, the percentage of men whose quality of life is substantially affected is much lower.

  • 35. Arnsrud Godtman, Rebecka
    et al.
    Månsson, Marianne
    Bratt, Ola
    Robinsson, David
    Johansson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Kjölhede, Henrik
    Development and validation of a prediction model for identifying men with intermediate- or high-risk prostate cancer for whom bone imaging is unnecessary: a nation-wide population-based study2019In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, no 6, p. 378-384Article in journal (Refereed)
    Abstract [en]

    Objective: To develop and validate a nomogram that identifies men for whom bone scan is unnecessary.

    Material and methods: The study datasets were derived from the National Prostate Cancer Register (NPCR) of Sweden. All men in the NPCR ≤80 years of age who were diagnosed with intermediate- or high-risk prostate cancer and who had pretreatment bone imaging (99mTc MDP scintigraphy, plain x-ray, computed tomography, magnetic resonance imaging, and/or positron emission tomography fused with computed tomography) were included. Men diagnosed from 2015–2016 formed a development dataset and men diagnosed in 2017 formed a validation dataset. Outcome was metastasis on bone imaging as registered in NPCR. Multivariable logistic regression was used to develop a nomogram.

    Results: In the development dataset 482/5084 men (10%) had bone metastasis, the corresponding percentage in the validation dataset was 282/2554 (11%). Gleason grade group, clinical T stage, and prostate-specific antigen were included in the final model. Discrimination and calibration were satisfactory in both the development (AUC 0.80, 95% CI 0.78–0.82) and validation dataset (AUC 0.80, 95% CI, 0.77–0.82). Compared with using the EAU guidelines’ recommendation for selecting men for imaging, using the nomogram with a cut-off at 4% chance of bone metastasis, would have avoided imaging in 519/2068 men (25%) and miss bone metastasis in 10/519 (2%) men in the validation dataset.

    Conclusion: By use of our nomogram, bone scans of men with prostate cancer can be avoided in a large proportion of men.

  • 36.
    Arthur, R.
    et al.
    Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England;Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
    Williams, R.
    Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.
    Malmstrom, H.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden;Swedish Orphan Biovitrum, Stockholm, Sweden.
    Lambe, M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Hammar, N.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden;AstraZeneca, Global Med Dev Med Evidence & Observat Res, Stockholm, Sweden.
    Walldius, G.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.
    Robinsson, D.
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Jungner, I.
    Karolinska Inst, Dept Clin Epidemiol, Stockholm, Sweden;CALAB Res, Stockholm, Sweden.
    Van Hemelrijck, M.
    Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England;Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.
    Serum inflammatory markers in relation to prostate cancer severity and death in the Swedish AMORIS study2018In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 142, no 11, p. 2254-2262Article in journal (Refereed)
    Abstract [en]

    Inflammation is a well-documented driver of cancer development and progression. However, little is known about its role in prostate carcinogenesis. Thus, we examined the association of C-reactive protein (CRP), haptoglobin, albumin and white blood cells (WBC) with prostate cancer (PCa) severity (defined by PCa risk category and clinicopathological characteristics) and progression (defined by PCa death). We selected 8,471 Swedish men with newly diagnosed PCa who had exposure measurements taken approximately 14 years prior to diagnosis. We calculated odds ratio (OR) and 95% confidence interval (CI) for the associations between the inflammatory markers and PCa severity using logistic regression, while Cox proportional hazard regression was used for the associations with overall and PCa death. Serum CRP levels were associated with increased odds of high risk and metastatic PCa, and high PSA levels (20 mu g/L) (OR: 1.29; 95% CI: 1.06-1.56, 1.32; 1.05-1.65 and 1.51; 1.26-1.81, respectively). Similarly, higher haptoglobin levels were associated with increased odds of metastatic PCa, high PSA level and possibly high grade PCa (1.38; 1.10-1.74, 1.50; 1.17-1.93 and 1.25; 1.00-1.56, respectively). Albumin was positively associated with Gleason 4+3 tumour (1.38; 1.02-1.86) and overall death (HRunit increase in log: 1.60; 95% CI: 1.11-2.30), but inversely associated with high risk PCa and high PSA levels (20 mu g/L) (0.71; 0.56-0.89 and 0.72; 0.5 9-0.90). WBC was associated with increased odds of T3-T4 PCa. Except for albumin, none of these markers were associated with PCa death or overall death. Systemic inflammation as early as 14 years prior to diagnosis may influence prostate cancer severity. What's new? High levels of C-reactive protein can presage a particularly malignant prostate cancer, new results show. Cancers certainly arise in the wake of chronic inflammation, but it's not known exactly how markers of inflammation initiate prostate cancer. Here, the authors show that systemic inflammation can worsen the severity of the cancer, even if it occurred long before the cancer's onset. High levels of CRP and haptoglobin, they found, were associated with prostate cancer with high PSA and metastasis. The question remains whether inflammation pushes cancer cells into a more malignant mode, or selects for the more dangerous cells early on.

  • 37.
    Asad, Danna
    et al.
    Umeå Univ, Dept Surg & Perioperat Sci Urol & Androl, S-90185 Umeå, Sweden..
    Styrke, Johan
    Umeå Univ, Dept Surg & Perioperat Sci Urol & Androl, S-90185 Umeå, Sweden..
    Hagsheno, Mohammad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Johansson, Markus
    Umeå Univ, Dept Surg & Perioperat Sci Urol & Androl, S-90185 Umeå, Sweden..
    Huge, Ylva
    Linköping Univ, Dept Clin & Expt Med, Div Urol, Linköping, Sweden..
    Svensson, Johan
    Umeå Univ, Umeå Sch Business Econ & Stat USBE, Dept Stat, Umeå, Sweden..
    Pelander, Sofia
    Linköping Univ, Dept Clin & Expt Med, Div Urol, Linköping, Sweden..
    Lauer, Jan
    Nyköping Cty Hosp, Dept Surg, Nyköping, Sweden..
    Netterling, Hans
    Umeå Univ, Dept Surg & Perioperat Sci Urol & Androl, S-90185 Umeå, Sweden..
    Aljabery, Firas
    Linköping Univ, Dept Clin & Expt Med, Div Urol, Linköping, Sweden..
    Sherif, Amir
    Umeå Univ, Dept Surg & Perioperat Sci Urol & Androl, S-90185 Umeå, Sweden..
    A prospective multicenter study of visual response-evaluation by cystoscopy in patients undergoing neoadjuvant chemotherapy for muscle invasive urinary bladder cancer2022In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 56, no 1, p. 20-26Article in journal (Refereed)
    Abstract [en]

    Purpose To evaluate a method of transurethral visual response-staging in patients with urothelial muscle-invasive urinary bladder cancer (MIBC), undergoing neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). Methods A prospective study at four Swedish cystectomy centers, cystoscopy was performed after final NAC-cycle for MIBC. Fifty-six participants underwent cystoscopy for visual staging of the tumor immediately pre-RC. Visual assessments were correlated to pathoanatomical outcomes post-RC. Results Seventeen tumors were classified as complete response (CR), i.e. pT0. Twenty-five patients had residual MIBC and 14 had non-muscle invasive residual tumors (NMIBC). Of the 39 patients with residual tumor, 25 were correctly identified visually (64%). Eleven patients were pN+. The diagnostic accuracy of cystoscopy to correctly identify complete response or remaining tumor was 70% (CI = 56-81%) with a sensitivity of 64% (CI = 47-79%), specificity 82% (CI = 57-96%), PPV 89% (CI = 74-96%) and NPV 50% (CI =38-61%). Twenty-eight cystoscopy evaluations showed signs of residual tumors and 3/28 (11%) were false positive. In 4/14 patients assessed having residual NMIBC the estimates were correct, 8/14 had histopathological MIBC and 2/14 had CR. In 11/14 patients (79%), the suggested visual assessment of MIBC was correct, 2/14 had NMIBC and 1/14 had CR. Twenty-eight cystoscopies had negative findings, 14 were false negatives (50%), when cystoscopy falsely predicted pT0. Among them there were eight patients with pTa, pT1 or pTis and six MIBC-tumors. In 17 patients with histopathological pT0, 14 were correctly identified with cystoscopy (82%). Conclusion Cystoscopy after the final NAC-cycle cannot robustly differentiate between NAC-responders and non-responders. Visually, negative MIBC-status cannot be determined safely.

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  • 38.
    Assel, Melissa
    et al.
    Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
    Dahlin, Anders
    Lund University.
    Ulmert, David
    Lund Univerity; Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
    Bergh, Anders
    Umeå University.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Umeå University.
    Lilja, Hans
    Lund University; University of Oxford; Memorial Sloan Kettering Cancer Center, New York, NY, USA.
    Vickers, Andrew J.
    Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
    Association Between Lead Time and Prostate Cancer Grade: Evidence of Grade Progression from Long-term Follow-up of Large Population-based Cohorts Not Subject to Prostate-specific Antigen Screening2018In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 73, no 6, p. 961-967Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Lead time (LT) is of key importance in early detection of cancer, but cannot be directly measured. We have previously provided LT estimates for prostate cancer (PCa) using archived blood samples from cohorts followed for many years without screening.

    OBJECTIVE: To determine the association between LT and PCa grade at diagnosis to provide an insight into whether grade progresses or is stable over time.

    DESIGN, SETTING, AND PARTICIPANTS: The setting was three long-term epidemiologic studies in Sweden including men not subject to prostate-specific antigen (PSA) screening. The cohort included 1041 men with PSA of 3-10 ng/ml at blood draw and subsequently diagnosed with PCa with grade data available.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable logistic regression was used to predict high-grade (Gleason grade group ≥2 or World Health Organization grade 3) versus low-grade PCa at diagnosis in terms of LT, defined as the time between the date of elevated PSA and the date of PCa diagnosis with adjustment for cohort and age.

    RESULTS AND LIMITATIONS: The probability that PCa would be high grade at diagnosis increased with LT. Among all men combined, the risk of high-grade disease increased with LT (odds ratio 1.13, 95% confidence interval [CI] 1.10-1.16; p<0.0001), with no evidence of differences in effect by age group or cohort. Higher PSA predicted shorter LT by 0.46 yr (95% CI 0.28-0.64; p<0.0001) per 1 ng/ml increase in PSA. However, there was no interaction between PSA and grade, suggesting that the longer LT for high-grade tumors is not simply related to age. Limitations include the assumption that men with elevated PSA and subsequently diagnosed with PCa would have had biopsy-detectable PCa at the time of PSA elevation.

    CONCLUSIONS: Our data support grade progression, whereby following a prostate over time would reveal transitions from benign to low-grade and then high-grade PCa.

    PATIENT SUMMARY: Men with a longer lead time between elevated prostate-specific antigen and subsequent prostate cancer diagnosis were more likely to have high-grade cancers at diagnosis.

  • 39. Augsten, Martin
    et al.
    Hägglöf, Christina
    Olsson, Eleonor
    Stolz, Claudia
    Tsagozis, Panagiotis
    Levchenko, Tetyana
    Frederick, Mitchell J.
    Borg, Åke
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Egevad, Lars
    Östman, Arne
    CXCL14 is an autocrine growth factor for fibroblasts and acts as a multi-modal stimulator of prostate tumor growth2009In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 106, no 9, p. 3414-3419Article in journal (Refereed)
    Abstract [en]

    This study explored the role of secreted fibroblast-derived factors in prostate cancer growth. Analyses of matched normal and tumor tissue revealed up-regulation of CXCL14 in cancer-associated fibroblasts of a majority of prostate cancer. Fibroblasts over-expressing CXCL14 promoted the growth of prostate cancer xenografts, and increased tumor angiogenesis and macrophage infiltration. Mechanistic studies demonstrated that autocrine CXCL14-stimulation of fibroblasts stimulate migration and ERK-dependent proliferation of fibroblasts. CXCL14-stimulation of monocyte migration was also demonstrated. Furthermore, CXCL14-producing fibroblasts, but not recombinant CXCL14, enhanced in vitro proliferation and migration of prostate cancer cells and in vivo angiogenesis. These studies thus identify CXCL14 as a novel autocrine stimulator of fibroblast growth and migration, with multi-modal tumor-stimulatory activities. In more general terms, our findings suggest autocrine stimulation of fibroblasts as a previously unrecognized mechanism for chemokine-mediated stimulation of tumor growth, and suggest a novel mechanism whereby cancer-associated fibroblasts achieve their pro-tumorigenic phenotype.

  • 40.
    Austin, Paul F.
    et al.
    Washington Univ, St Louis Childrens Hosp, Div Urol, St Louis, MO 63110 USA..
    Bauer, Stuart B.
    Harvard Univ, Childrens Hosp, Sch Med, Dept Urol, Boston, MA 02115 USA..
    Bower, Wendy
    Skejby Univ Hosp, Pediat Nephrol Sect, Aarhus, Denmark..
    Chase, Janet
    Cabrini Hosp, Childrens Ctr, Melbourne, Vic, Australia..
    Franco, Israel
    New York Med Coll, Valhalla, NY 10595 USA..
    Hoebeke, Piet
    Ghent Univ Hosp, Pediat Urol & Nephrol, Ghent, Belgium..
    Rittig, Soren
    Skejby Univ Hosp, Pediat Nephrol Sect, Aarhus, Denmark..
    Vande Walle, Johan
    Ghent Univ Hosp, Pediat Urol & Nephrol, Ghent, Belgium..
    von Gontard, Alexander
    Saarland Univ Hosp, Dept Child & Adolescent Psychiat, Saarbrucken, Germany..
    Wright, Anne
    St Thomas Hosp, Evelina Childrens Hosp, Pediat, London, England..
    Yang, Stephen S.
    Buddhist Med Fdn, Taipei Tzu Chi Hosp, Div Urol, New Taipei, Taiwan.;Buddhist Tzu Chi Univ, Sch Med, Hualien, Taiwan..
    Nevéus, Tryggve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    The standardization of terminology of lower urinary tract function in children and adolescents: Update report from the standardization committee of the International Children's Continence Society2016In: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 35, no 4, p. 471-481Article in journal (Refereed)
    Abstract [en]

    AimThe impact of the original International Children's Continence Society (ICCS) terminology document on lower urinary tract (LUT) function resulted in the global establishment of uniformity and clarity in the characterization of LUT function and dysfunction in children across multiple healthcare disciplines. The present document serves as a stand-alone terminology update reflecting refinement and current advancement of knowledge on pediatric LUT function. MethodsA variety of worldwide experts from multiple disciplines within the ICCS leadership who care for children with LUT dysfunction were assembled as part of the standardization committee. A critical review of the previous ICCS terminology document and the current literature was performed. Additionally, contributions and feedback from the multidisciplinary ICCS membership were solicited. ResultsFollowing a review of the literature over the last 7 years, the ICCS experts assembled a new terminology document reflecting current understanding of bladder function and LUT dysfunction in children using the resources from the literature review, expert opinion and ICCS member feedback. ConclusionsThe present ICCS terminology document provides a current and consensus update to the evolving terminology and understanding of LUT function in children.

  • 41. Babitt, Jodie L.
    et al.
    Eisenga, Michele F.
    Haase, Volker H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Vanderbilt University Medical Center; Vanderbilt University School of Medicine.
    Kshirsagar, Abhijit V.
    Levin, Adeera
    Locatelli, Francesco
    Małyszko, Jolanta
    Swinkels, Dorine W.
    Tarng, Der-Cherng
    Cheung, Michael
    Jadoul, Michel
    Winkelmayer, Wolfgang C.
    Drüeke, Tilman B.
    Controversies in Optimal Anemia Management: Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference2021In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 99, no 6, p. 1280-1295Article in journal (Refereed)
    Abstract [en]

    In chronic kidney disease (CKD), anemia and disordered iron homeostasis are prevalent and associated with significant adverse consequences. In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) issued an anemia guideline for managing the diagnosis, evaluation, and treatment of anemia in CKD. Since then, new data have accrued from basic research, epidemiological studies, and randomized trials that warrant a re-examination of previous recommendations. Therefore, in 2019, KDIGO decided to convene two Controversies Conferences to review the latest evidence, explore new and ongoing controversies, assess change implications for the current KDIGO anemia guideline, and propose a research agenda. The first conference, described here, focused mainly on iron-related issues, including the contribution of disordered iron homeostasis to the anemia of CKD, diagnostic challenges, available and emerging iron therapies, treatment targets, and patient outcomes. The second conference will discuss issues more specifically related to erythropoiesis-stimulating agents, including epoetins and hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs). Here we provide a concise overview of the consensus points and controversies resulting from the first conference and prioritize key questions which need to be answered by future research.

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  • 42. Bakris, George L
    et al.
    Agarwal, Rajiv
    Anker, Stefan D
    Pitt, Bertram
    Ruilope, Luis M
    Nowack, Christina
    Kolkhof, Peter
    Ferreira, Anna C
    Schloemer, Patrick
    Filippatos, Gerasimos
    Design and Baseline Characteristics of the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease Trial.2019In: American Journal of Nephrology, ISSN 0250-8095, E-ISSN 1421-9670, Vol. 50, no 5, p. 333-344Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Among diabetics, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality, and progression of their underlying disease. Finerenone is a novel, non-steroidal, selective mineralocorticoid-receptor antagonist which has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD), while revealing only a low risk of hyperkalemia. However, the effect of finerenone on renal and CV outcomes has not been investigated in long-term trials yet.

    METHODS: The Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease -(FIDELIO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important renal and CV outcomes in T2D patients with CKD. FIDELIO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 5.5 years. FIDELIO-DKD randomized 5,734 patients with an estimated glomerular filtration rate (eGFR) ≥25-<75 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio ≥30-≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of kidney failure, a sustained decrease of eGFR ≥40% from baseline over at least 4 weeks, or renal death.

    CONCLUSION: FIDELIO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of renal and CV events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen.

  • 43. Bakris, George L
    et al.
    Agarwal, Rajiv
    Anker, Stefan D
    Pitt, Bertram
    Ruilope, Luis M
    Rossing, Peter
    Kolkhof, Peter
    Nowack, Christina
    Schloemer, Patrick
    Joseph, Amer
    Filippatos, Gerasimos
    Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes2020In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 383, no 23, p. 2219-2229Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Finerenone, a nonsteroidal, selective mineralocorticoid receptor antagonist, reduced albuminuria in short-term trials involving patients with chronic kidney disease (CKD) and type 2 diabetes. However, its long-term effects on kidney and cardiovascular outcomes are unknown.

    METHODS: In this double-blind trial, we randomly assigned 5734 patients with CKD and type 2 diabetes in a 1:1 ratio to receive finerenone or placebo. Eligible patients had a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 30 to less than 300, an estimated glomerular filtration rate (eGFR) of 25 to less than 60 ml per minute per 1.73 m2 of body-surface area, and diabetic retinopathy, or they had a urinary albumin-to-creatinine ratio of 300 to 5000 and an eGFR of 25 to less than 75 ml per minute per 1.73 m2. All the patients were treated with renin-angiotensin system blockade that had been adjusted before randomization to the maximum dose on the manufacturer's label that did not cause unacceptable side effects. The primary composite outcome, assessed in a time-to-event analysis, was kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes. The key secondary composite outcome, also assessed in a time-to-event analysis, was death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure.

    RESULTS: During a median follow-up of 2.6 years, a primary outcome event occurred in 504 of 2833 patients (17.8%) in the finerenone group and 600 of 2841 patients (21.1%) in the placebo group (hazard ratio, 0.82; 95% confidence interval [CI], 0.73 to 0.93; P = 0.001). A key secondary outcome event occurred in 367 patients (13.0%) and 420 patients (14.8%) in the respective groups (hazard ratio, 0.86; 95% CI, 0.75 to 0.99; P = 0.03). Overall, the frequency of adverse events was similar in the two groups. The incidence of hyperkalemia-related discontinuation of the trial regimen was higher with finerenone than with placebo (2.3% and 0.9%, respectively).

    CONCLUSIONS: In patients with CKD and type 2 diabetes, treatment with finerenone resulted in lower risks of CKD progression and cardiovascular events than placebo. (Funded by Bayer; FIDELIO-DKD ClinicalTrials.gov number, NCT02540993.).

  • 44.
    Bamberg, Krister
    et al.
    AstraZeneca, BioPharmaceut R&D, Translat Sci & Expt Med, Res & Early Dev,Cardiovasc Renal & Metab, Gothenburg, Sweden..
    William-Olsson, Lena
    AstraZeneca, BioPharmaceut R&D, Biosci Renal Res & Early Dev, Cardiovasc Renal & Metab, Gothenburg, Sweden..
    Johansson, Ulrika
    AstraZeneca, BioPharmaceut R&D, Biosci Renal Res & Early Dev, Cardiovasc Renal & Metab, Gothenburg, Sweden..
    Arner, Anders
    Lund Univ, Dept Clin Sci Lund, Lund, Sweden..
    Hartleib-Geschwindner, Judith
    AstraZeneca, BioPharmaceut R&D, Projects Res & Early Dev, Cardiovasc Renal & Metab, Gothenburg, Sweden..
    Sällström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Electrolyte handling in the isolated perfused rat kidney: demonstration of vasopressin V2-receptor-dependent calcium reabsorption2020In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 125, no 4, p. 274-280Article in journal (Refereed)
    Abstract [en]

    Background The most profound effect of vasopressin on the kidney is to increase water reabsorption through V-2-receptor (V2R) stimulation, but there are also data suggesting effects on calcium transport. To address this issue, we have established an isolated perfused kidney model with accurate pressure control, to directly study the effects of V2R stimulation on kidney function, isolated from systemic effects. Methods The role of V2R in renal calcium handling was studied in isolated rat kidneys using a new pressure control system that uses a calibration curve to compensate for the internal pressure drop up to the tip of the perfusion cannula. Results Kidneys subjected to V2R stimulation using desmopressin (DDAVP) displayed stable osmolality and calcium reabsorption throughout the experiment, whereas kidneys not administered DDAVP exhibited a simultaneous fall in urine osmolality and calcium reabsorption. Epithelial sodium channel (ENaC) inhibition using amiloride resulted in a marked increase in potassium reabsorption along with decreased sodium reabsorption. Conclusions A stable isolated perfused kidney model with computer-controlled pressure regulation was developed, which retained key physiological functions. The preparation responds to pharmacological inhibition of ENaC channels and activation of V2R. Using the model, the dynamic effects of V2R stimulation on calcium handling and urine osmolality could be visualised. The study thereby provides evidence for a stimulatory role of V2R in renal calcium reabsorption.

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  • 45.
    Bandert, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Research and Development, Gävleborg. Department of Anaesthesiology and Intensive Care, Gävle Hospital, Lasarettvägen 1, 80324, Gävle, Sweden.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory.
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Smekal, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    In an endotoxaemic model, antibiotic clearance can be affected by different central venous catheter positions, during renal replacement therapy2023In: Intensive Care Medicine Experimental, E-ISSN 2197-425X, Vol. 11, no 1, article id 32Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In intensive care, different central venous catheters (CVC) are often used for infusion of drugs. If a patient is treated with continuous renal replacement therapy (CRRT) a second catheter, a central venous dialysis catheter (CVDC), is needed. Placing the catheters close together might pose a risk that a drug infused in a CVC could be directly aspirated into a CRRT machine and cleared from the blood without giving the effect intended. The purpose of this study was to elucidate if drug clearance is affected by different catheter placement, during CRRT. In this endotoxaemic animal model, an infusion of antibiotics was administered in a CVC placed in the external jugular vein (EJV). Antibiotic clearance was compared, whether CRRT was through a CVDC placed in the same EJV, or in a femoral vein (FV). To reach a target mean arterial pressure (MAP), noradrenaline was infused through the CVC and the dose was compared between the CDVDs.

    RESULTS: The main finding in this study was that clearance of antibiotics was higher when both catheter tips were in the EJV, close together, compared to in different vessels, during CRRT. The clearance of gentamicin was 21.0 ± 7.3 vs 15.5 ± 4.2 mL/min (p 0.006) and vancomycin 19.3 ± 4.9 vs 15.8 ± 7.1 mL/min (p 0.021). The noradrenaline dose to maintain a target MAP also showed greater variance with both catheters in the EJV, compared to when catheters were placed in different vessels.

    CONCLUSION: The results in this study indicate that close placement of central venous catheter tips could lead to unreliable drug concentration, due to direct aspiration, during CRRT.

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  • 46. Bangalore, Sripal
    et al.
    Maron, David J
    O'Brien, Sean M
    Fleg, Jerome L
    Kretov, Evgeny I
    Briguori, Carlo
    Kaul, Upendra
    Reynolds, Harmony R
    Mazurek, Tomasz
    Sidhu, Mandeep S
    Berger, Jeffrey S
    Mathew, Roy O
    Bockeria, Olga
    Broderick, Samuel
    Pracon, Radoslaw
    Herzog, Charles A
    Huang, Zhen
    Stone, Gregg W
    Boden, William E
    Newman, Jonathan D
    Ali, Ziad A
    Mark, Daniel B
    Spertus, John A
    Alexander, Karen P
    Chaitman, Bernard R
    Chertow, Glenn M
    Hochman, Judith S
    Management of Coronary Disease in Patients with Advanced Kidney Disease.2020In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 382, no 17, p. 1608-1618Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease.

    METHODS: We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest.

    RESULTS: At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P = 0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P = 0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P = 0.03).

    CONCLUSIONS: Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA-CKD ClinicalTrials.gov number, NCT01985360.).

  • 47.
    Barbour, Sean J.
    et al.
    Univ British Columbia, Div Nephrol, 2775 Laurel St,Fifth Floor, Vancouver, BC V5Z 1M9, Canada;BC Renal, Vancouver, BC, Canada.
    Coppo, Rosanna
    Regina Margherita Childrens Univ Hosp, Turin, Italy.
    Zhang, Hong
    Peking Univ, Inst Nephrol, Beijing, Peoples R China.
    Liu, Zhi-Hong
    Nanjing Univ, Sch Med, Nanjing, Jiangsu, Peoples R China.
    Suzuki, Yusuke
    Juntendo Univ, Fac Med, Tokyo, Japan.
    Matsuzaki, Keiichi
    Juntendo Univ, Fac Med, Tokyo, Japan.
    Katafuchi, Ritsuko
    Natl Fukuoka Higashi Med Ctr, Fukuoka, Fukuoka, Japan.
    Er, Lee
    BC Renal, Vancouver, BC, Canada.
    Espino-Hernandez, Gabriela
    BC Renal, Vancouver, BC, Canada.
    Kim, S. Joseph
    Univ Toronto, Div Nephrol, Toronto, ON, Canada.
    Reich, Heather N.
    Univ Toronto, Div Nephrol, Toronto, ON, Canada.
    Feehally, John
    Leicester Gen Hosp, John Walls Renal Unit, Leicester, Leics, England.
    Cattran, Daniel C.
    Univ Toronto, Div Nephrol, Toronto, ON, Canada.
    Russo, M. L.
    Fdn Ric Molinette, Turin, Italy.
    Troyanov, S.
    Hop Sacre Coeur Montreal, Dept Med, Div Nephrol, Montreal, PQ, Canada;Hop Sacre Coeur Montreal, Dept Med, Div Nephrol, Montreal, PQ, Canada.
    Cook, H. T.
    Imperial Coll, Dept Med, Ctr Complement & Inflammat Res, London, England.
    Roberts, I.
    Oxford Univ Hosp NHS Fdn Trust, John Radcliffe Hosp, Dept Cellular Pathol, Oxford, England.
    Tesar, V.
    Charles Univ Prague, Fac Med 1, Dept Nephrol, Prague, Czech Republic;Charles Univ Prague, Gen Univ Hosp, Prague, Czech Republic.
    Maixnerova, D.
    Charles Univ Prague, Fac Med 1, Dept Nephrol, Prague, Czech Republic;Charles Univ Prague, Gen Univ Hosp, Prague, Czech Republic.
    Lundberg, S.
    Karolinska Inst, Dept Clin Sci, Nephrol Unit, Stockholm, Sweden.
    Gesualdo, L.
    Univ Bah Aldo Moro, Dept Nephrol Emergency & Organ Transplantat, Foggia, Italy.
    Emma, F.
    Bambino Gesu Pediat Hosp, IRCCS, Dept Pediat Subspecialties, Div Nephrol, Rome, Italy.
    Fuiano, L.
    Bambino Gesu Pediat Hosp, IRCCS, Dept Pediat Subspecialties, Div Nephrol, Rome, Italy.
    Beltrame, G.
    San Giovanni Bosco Hosp, Nephrol & Dialysis Unit, Turin, Italy;Univ Turin, Turin, Italy.
    Rollino, C.
    San Giovanni Bosco Hosp, Nephrol & Dialysis Unit, Turin, Italy;Univ Turin, Turin, Italy.
    Amore, A.
    Regina Margherita Childrens Hosp, Nephrol Unit, Turin, Italy;Univ Turin, Regina Margherita Childrens Hosp, Nephrol Dialysis & Transplantat Unit, Turin, Italy.
    Camilla, R.
    Regina Margherita Childrens Hosp, Nephrol Unit, Turin, Italy.
    Peruzzi, L.
    Regina Margherita Childrens Hosp, Nephrol Unit, Turin, Italy.
    Praga, M.
    Hosp 12 Octubre, Nephrol Unit, Madrid, Spain.
    Feriozzi, S.
    Belcolle Hosp, Nephrol Unit, Viterbo, Italy.
    Polci, R.
    Belcolle Hosp, Nephrol Unit, Viterbo, Italy.
    Segoloni, G.
    Univ Turin, Turin, Italy;Citta Salute & Sci Hosp, Dept Med Sci, Div Nephrol Dialysis & Transplantat, Turin, Italy.
    Colla, L.
    Univ Turin, Turin, Italy;Citta Salute & Sci Hosp, Dept Med Sci, Div Nephrol Dialysis & Transplantat, Turin, Italy.
    Pani, A.
    G Brotzu Hosp, Nephrol Unit, Cagliari, Italy.
    Piras, D.
    G Brotzu Hosp, Nephrol Unit, Cagliari, Italy.
    Angioi, A.
    G Brotzu Hosp, Nephrol Unit, Cagliari, Italy.
    Cancarini, G.
    Spedali Civili Univ Hosp, Nephrol Unit, Brescia, Italy.
    Ravera, S.
    Spedali Civili Univ Hosp, Nephrol Unit, Brescia, Italy.
    Durlik, M.
    Med Univ Warsaw, Dept Transplantat Med Nephrol & Internal Med, Warsaw, Poland.
    Moggia, E.
    Santa Croce Hosp, Nephrol Unit, Cuneo, Italy.
    Ballarin, J.
    Fdn Puigvert, Dept Nephrol, Barcelona, Spain.
    Di Giulio, S.
    San Camillo Forlanini Hosp, Nephrol Unit, Rome, Italy.
    Pugliese, F.
    Policlin Umberto Univ Hosp, Dept Nephrol, Rome, Italy.
    Serriello, I.
    Policlin Umberto Univ Hosp, Dept Nephrol, Rome, Italy.
    Caliskan, Y.
    Istanbul Univ, Istanbul Fac Med, Dept Internal Med, Div Nephrol, Istanbul, Turkey.
    Sever, M.
    Istanbul Univ, Istanbul Fac Med, Dept Internal Med, Div Nephrol, Istanbul, Turkey.
    Kilicaslan, I.
    Istanbul Univ, Istanbul Fac Med, Dept Pathol, Istanbul, Turkey.
    Locatelli, F.
    ASST Lecco, Alessandro Manzoni Hosp, Dept Nephrol & Dialysis, Lecce, Italy.
    Del Vecchio, L.
    ASST Lecco, Alessandro Manzoni Hosp, Dept Nephrol & Dialysis, Lecce, Italy.
    Wetzels, J. F. M.
    Radboud Univ Nijmegen, Med Ctr, Dept Nephrol, Nijmegen, Netherlands.
    Peters, H.
    Radboud Univ Nijmegen, Med Ctr, Dept Nephrol, Nijmegen, Netherlands.
    Berg, U.
    Dept Clin Sci Intervent & Technol, Div Pediat, Huddinge, Sweden.
    Carvalho, F.
    Hosp Curry Cabral, Nephrol Unit, Lisbon, Portugal.
    da Costa Ferreira, A. C.
    Hosp Curry Cabral, Nephrol Unit, Lisbon, Portugal.
    Maggio, M.
    Hosp Maggiore Lodi, Nephrol Unit, Lodi, Italy.
    Wiecek, A.
    Silesian Univ Med, Dept Nephrol Endocrinol & Metab Dis, Katowice, Poland.
    Ots-Rosenberg, M.
    Tartu Univ Clin, Nephrol Unit, Tartu, Estonia.
    Magistroni, R.
    Policlin Modena & Reggio Emilia, Dept Nephrol, Modena, Italy.
    Topaloglu, R.
    Hacettepe Univ, Dept Pediat Nephrol & Rheumatol, Ankara, Turkey.
    Bilginer, Y.
    Hacettepe Univ, Dept Pediat Nephrol & Rheumatol, Ankara, Turkey.
    D'Amico, M.
    St Anna Hosp, Nephrol Unit, Como, Italy.
    Stangou, M.
    Aristotle Univ Thessaloniki, Hippokrat Gen Hosp, Dept Nephrol, Thessaloniki, Greece.
    Giacchino, F.
    Ivrea Hosp, Nephrol Unit, Ivrea, Italy.
    Goumenos, D.
    Univ Hosp Patras, Dept Nephrol, Patras, Greece.
    Kalliakmani, P.
    Univ Hosp Patras, Dept Nephrol, Patras, Greece.
    Gerolymos, M.
    Univ Hosp Patras, Dept Nephrol, Patras, Greece.
    Galesic, K.
    Univ Hosp Dubrava, Dept Nephrol, Zagreb, Croatia.
    Geddes, C.
    Western Infirm Glasgow, Renal Unit, Glasgow, Lanark, Scotland;Western Infirm & Associated Hosp, Renal Unit, Glasgow, Lanark, Scotland.
    Siamopoulos, K.
    Univ Ioannina, Med Sch, Nephrol Unit, Ioannina, Greece.
    Balafa, O.
    Univ Ioannina, Med Sch, Nephrol Unit, Ioannina, Greece.
    Galliani, M.
    S Pertini Hosp, Nephrol Unit, Rome, Italy.
    Stratta, P.
    Piemonte Orientale Univ, Maggiore Carita Hosp, Dept Nephrol, Novara, Italy.
    Quaglia, M.
    Piemonte Orientale Univ, Maggiore Carita Hosp, Dept Nephrol, Novara, Italy.
    Bergia, R.
    Infermi Hosp, Nephrol Unit, Biella, Italy.
    Cravero, R.
    Infermi Hosp, Nephrol Unit, Biella, Italy.
    Salvadori, M.
    Careggi Hosp, Dept Nephrol, Florence, Italy.
    Cirami, L.
    Careggi Hosp, Dept Nephrol, Florence, Italy.
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Smerud, Hilde Kloster
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Ferrario, F.
    San Gerardo Hosp, Nephropathol Unit, Monza, Italy;San Gerardo Hosp, Nephropathol Unit, Monza, Italy;San Carlo Borromeo Hosp, Renal Immunopathol Ctr, Milan, Italy.
    Stellato, T.
    San Gerardo Hosp, Nephropathol Unit, Monza, Italy.
    Egido, J.
    Fdn Jimenez Diaz, Dept Nephrol, Madrid, Spain.
    Martin, C.
    Fdn Jimenez Diaz, Dept Nephrol, Madrid, Spain.
    Floege, J.
    Univ Aachen, Med Klin 2, Nephrol & Immunol, Aachen, Germany.
    Eitner, F.
    Univ Aachen, Med Klin 2, Nephrol & Immunol, Aachen, Germany.
    Lupo, A.
    Univ Verona, Dept Nephrol, Verona, Italy.
    Bernich, P.
    Univ Verona, Dept Nephrol, Verona, Italy.
    Mene, R.
    S Andrea Hosp, Dept Nephrol, Rome, Italy.
    Morosetti, M.
    Grassi Hosp, Nephrol Unit, Ostia, Italy.
    van Kooten, C.
    Leiden Univ, Med Ctr, Dept Nephrol, Leiden, Netherlands.
    Rabelink, T.
    Leiden Univ, Med Ctr, Dept Nephrol, Leiden, Netherlands.
    Reinders, M. E. J.
    Leiden Univ, Med Ctr, Dept Nephrol, Leiden, Netherlands.
    Boria Grinyo, J. M.
    Bellvitge Hosp, Dept Nephrol, Barcelona, Spain.
    Cusinato, S.
    Borgomanero Hosp, Nephrol Unit, Borgomanero, Italy.
    Benozzi, L.
    Borgomanero Hosp, Nephrol Unit, Borgomanero, Italy.
    Savoldi, S.
    Civile Hosp, Nephrol Unit, Cirie, Italy.
    Licata, C.
    Civile Hosp, Nephrol Unit, Cirie, Italy.
    Mizerska-Wasiak, M.
    Med Univ Warsaw, Dept Pediat, Warsaw, Poland.
    Martina, G.
    Chivasso Hosp, Nephrol Unit, Chivasso, Italy.
    Messuerotti, A.
    Chivasso Hosp, Nephrol Unit, Chivasso, Italy.
    Dal Canton, A.
    San Matteo Hosp, Nephrol Unit, Pavia, Italy.
    Esposito, C.
    Maugeri Fdn, Nephrol Unit, Pavia, Italy.
    Migotto, C.
    Maugeri Fdn, Nephrol Unit, Pavia, Italy.
    Triolo, G.
    Nephrol Unit CTO, Turin, Italy.
    Mariano, F.
    Nephrol Unit CTO, Turin, Italy.
    Pozzi, C.
    Bassini Hosp, Nephrol Unit, Cinisello Balsamo, Italy.
    Boero, R.
    Martini Hosp, Nephrol Unit, Turin, Italy.
    Bellur, S.
    Oxford Univ Hosp NHS Fdn Trust, John Radcliffe Hosp, Dept Cellular Pathol, Oxford, England.
    Mazzucco, G.
    Univ Turin, Pathol Dept, Turin, Italy.
    Giannakakis, C.
    Sapienza Univ, Pathol Dept, Rome, Italy.
    Honsova, E.
    Inst Clin & Expt Med, Dept Clin & Transplant Pathol, Prague, Czech Republic.
    Sundelin, B.
    Karolinska Univ Hosp, Karolinska Inst, Dept Pathol & Cytol, Stockholm, Sweden.
    Di Palma, A. M.
    Aldo Moro Univ, Nephrol Unit, Foggia, Italy.
    Gutierrez, E.
    Univ Autonoma Madrid, Fdn Jimenez Diaz, Fdn Inst Invest Sanitarias, Renal Vasc & Diabet Res Lab, Madrid, Spain.
    Asunis, A. M.
    Brotzu Hosp, Dept Pathol, Cagliari, Italy.
    Barratt, J.
    Leicester Gen Hosp, John Walls Renal Unit, Leicester, Leics, England;Leicester Gen Hosp, John Walls Renal Unit, Leicester, Leics, England.
    Tardanico, R.
    Univ Brescia, Spedali Civili Hosp, Dept Pathol, Brescia, Italy.
    Perkowska-Ptasinska, A.
    Med Univ Warsaw, Dept Transplantat Med Nephrol & Internal Med, Warsaw, Poland.
    Arce Terroba, J.
    Fundacio Puigvert, Pathol Dept, Barcelona, Spain.
    Fortunato, M.
    S Croce Hosp, Pathol Dept, Cuneo, Italy.
    Pantzaki, A.
    Hippokrateion Hosp, Dept Pathol, Thessaloniki, Greece.
    Ozluk, Y.
    Istanbul Univ, Istanbul Fac Med, Dept Pathol, Istanbul, Turkey.
    Steenbergen, E.
    Radboud Univ Nijmegen, Med Ctr, Dept Pathol, Nijmegen, Netherlands.
    Soderberg, M.
    Dept Pathol Drug Safety & Metab, Huddinge, Sweden.
    Riispere, Z.
    Univ Tartu, Dept Pathol, Tartu, Estonia.
    Furci, L.
    Univ Modena, Pathol Dept, Modena, Italy.
    Orhan, D.
    Hacettepe Univ, Fac Med, Div Rheumatol, Dept Pediat, Ankara, Turkey.
    Kipgen, D.
    Queen Elizabeth Univ Hosp, Pathol Dept, Glasgow, Lanark, Scotland.
    Casartelli, D.
    Manzoni Hosp, Pathol Dept, Lecce, Italy.
    Ljubanovic, D. Galesic
    Univ Hosp Zagreb, Nephrol Dept, Zagreb, Croatia.
    Gakiopoulou, H.
    Univ Athens, Dept Pathol, Athens, Greece.
    Bertoni, E.
    Careggi Hosp, Nephrol Dept, Florence, Italy.
    Cannata Ortiz, P.
    UAM, IIS Fdn Jimenez Diaz, Pathol Dept, Madrid, Spain.
    Karkoszka, H.
    Med Univ Silesia, Nephrol Endocrinol & Metab Dis, Katowice, Poland.
    Groene, H. J.
    German Canc Res Ctr, Cellular & Mol Pathol, Heidelberg, Germany.
    Stoppacciaro, A.
    Sapienza Univ Rome, Osped St Andrea, Dept Clin & Mol Med, Surg Pathol Unit, Rome, Italy.
    Bajema, I.
    Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands.
    Bruijn, J.
    Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands;Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands.
    Fulladosa Oliveras, X.
    Bellvitge Univ Hosp, Nephrol Unit, Barcelona, Spain.
    Maldyk, J.
    Med Univ Warsaw, Childrens Clin Hosp, Div Pathomorphol, Warsaw, Poland.
    Loachim, E.
    Univ Ioannina, Med Sch, Dept Pathol, Ioannina, Greece.
    Bavbek, N.
    Vanderbilt Univ, Dept Pathol, Nashville, TN USA.
    Cook, T.
    Imperial Coll, London, England.
    Alpers, C.
    Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA.
    Berthoux, F.
    CHU St Etienne, Hop Nord, Dept Nephrol Dialysis & Renal Transplantat, St Etienne, France.
    Bonsib, S.
    LSU Hlth Sci Ctr, Dept Pathol, Shreveport, LA USA.
    D'Agati, V
    Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY USA.
    D'Amico, G.
    Fdn DAmico Ric Malattie Renali, Milan, Italy.
    Emancipator, S.
    Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA.
    Emmal, F.
    Bambino Gesu Childrens Hosp & Res Inst, Dept Nephrol & Urol, Div Nephrol & Dialysis, Rome, Italy.
    Fervenza, F.
    Mayo Clin, Div Nephrol & Hypertens, Rochester, MN USA.
    Florquin, S.
    Univ Amsterdam, Acad Med Ctr, Dept Pathol, Amsterdam, Netherlands.
    Fogo, A.
    Vanderbilt Univ, Dept Pathol, Nashville, TN USA.
    Groene, H.
    German Canc Res Ctr, Dept Cellular & Mol Pathol, Heidelberg, Germany.
    Haas, M.
    Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA.
    Hill, P.
    St Vincents Hosp, Melbourne, Vic, Australia.
    Hogg, R.
    Scott & White Med Ctr, Temple, TX USA.
    Hsu, S.
    Univ Florida, Coll Med, Div Nephrol Hypertens & Renal Transplantat, Gainesville, FL USA.
    Hunley, T.
    Vanderbilt Univ, Dept Pathol, Nashville, TN USA.
    Hladunewich, M.
    Jennette, C.
    Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27515 USA.
    Joh, K.
    East Natl Hosp, Clin Res Ctr Chiba, Div Immunopathol, Chiba, Japan.
    Julian, B.
    Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
    Kawamura, T.
    Jikei Univ, Sch Med, Div Nephrol & Hypertens, Tokyo, Japan;Jikei Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Tokyo, Japan.
    Lai, F.
    Chinese Univ Hong Kong, Hong Kong, Peoples R China.
    Leung, C.
    Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med, Hong Kong, Peoples R China.
    Li, L.
    Nanjing Univ, Sch Med, Jinling Hosp, Res Inst Nephrol, Nanjing, Jiangsu, Peoples R China.
    Li, P.
    Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med, Hong Kong, Peoples R China.
    Liu, Z.
    Nanjing Univ, Sch Med, Nanjing, Jiangsu, Peoples R China;Nanjing Univ, Sch Med, Jinling Hosp, Res Inst Nephrol, Nanjing, Jiangsu, Peoples R China.
    Massat, A.
    Mayo Clin, Div Nephrol & Hypertens, Rochester, MN USA.
    Mackinnon, B.
    Western Infirm & Associated Hosp, Renal Unit, Glasgow, Lanark, Scotland.
    Mezzano, S.
    Univ Austral Chile, Escuela Med, Dept Nefrol, Valdivia, Chile.
    Schena, F.
    Policlinico, Renal Dialysis & Transplant Unit, Bari, Italy.
    Tomino, Y.
    Juntendo Univ, Sch Med, Dept Internal Med, Div Nephrol, Tokyo, Japan.
    Walker, P.
    Nephropathol Associates, Little Rock, AR USA.
    Wang, H.
    Peking Univ, Inst Nephrol, Hosp 1, Renal Div, Beijing, Peoples R China.
    Weening, J.
    Erasmus MC, Rotterdam, Netherlands.
    Yoshikawa, N.
    Wakayama Med Univ, Dept Pediat, Wakayama, Japan.
    Zeng, Cai-Hong
    Nanjing Univ, Sch Med, Nanjing, Jiangsu, Peoples R China.
    Shi, Sufang
    Peking Univ, Inst Nephrol, Beijing, Peoples R China.
    Nogi, C.
    Juntendo Univ, Fac Med, Tokyo, Japan.
    Suzuki, H.
    Juntendo Univ, Fac Med, Tokyo, Japan;Juntendo Univ, Fac Med, Tokyo, Japan.
    Koike, K.
    Jikei Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Tokyo, Japan.
    Hirano, K.
    Jikei Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Tokyo, Japan.
    Yokoo, T.
    Jikei Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Tokyo, Japan.
    Hanai, M.
    Kurume Univ, Sch Med, Dept Med, Div Nephrol, Fukuoka, Fukuoka, Japan.
    Fukami, K.
    Kurume Univ, Sch Med, Dept Med, Div Nephrol, Fukuoka, Fukuoka, Japan.
    Takahashi, K.
    Fujita Hlth Univ, Sch Med, Dept Nephrol, Toyoake, Aichi, Japan.
    Yuzawa, Y.
    Fujita Hlth Univ, Sch Med, Dept Nephrol, Toyoake, Aichi, Japan.
    Niwa, M.
    Nagoya Univ, Grad Sch Med, Dept Nephrol, Nagoya, Aichi, Japan.
    Yasuda, Y.
    Nagoya Univ, Grad Sch Med, Dept Nephrol, Nagoya, Aichi, Japan.
    Maruyama, S.
    Nagoya Univ, Grad Sch Med, Dept Nephrol, Nagoya, Aichi, Japan.
    Ichikawa, D.
    St Marianna Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Kawasaki, Kanagawa, Japan.
    Suzuki, T.
    Juntendo Univ, Fac Med, Tokyo, Japan;St Marianna Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Kawasaki, Kanagawa, Japan.
    Shirai, S.
    St Marianna Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Kawasaki, Kanagawa, Japan.
    Fukuda, A.
    Miyazaki Univ, Fac Med, Dept Internal Med 1, Miyazaki, Japan.
    Fujimoto, S.
    Univ Miyazaki, Fac Med, Dept Hemovasc Med & Artificial Organs, Miyazaki, Japan.
    Trimarchi, H.
    Hosp Britanico, Div Nephrol, Buenos Aires, DF, Argentina.
    Evaluating a New International Risk-Prediction Tool in IgA Nephropathy2019In: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114, Vol. 179, no 7, p. 942-952Article in journal (Refereed)
    Abstract [en]

    Importance  Although IgA nephropathy (IgAN) is the most common glomerulonephritis in the world, there is no validated tool to predict disease progression. This limits patient-specific risk stratification and treatment decisions, clinical trial recruitment, and biomarker validation.

    Objective  To derive and externally validate a prediction model for disease progression in IgAN that can be applied at the time of kidney biopsy in multiple ethnic groups worldwide.

    Design, Setting, and Participants  We derived and externally validated a prediction model using clinical and histologic risk factors that are readily available in clinical practice. Large, multi-ethnic cohorts of adults with biopsy-proven IgAN were included from Europe, North America, China, and Japan.

    Main Outcomes and Measures  Cox proportional hazards models were used to analyze the risk of a 50% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease, and were evaluated using the R2D measure, Akaike information criterion (AIC), C statistic, continuous net reclassification improvement (NRI), integrated discrimination improvement (IDI), and calibration plots.

    Results  The study included 3927 patients; mean age, 35.4 (interquartile range, 28.0-45.4) years; and 2173 (55.3%) were men. The following prediction models were created in a derivation cohort of 2781 patients: a clinical model that included eGFR, blood pressure, and proteinuria at biopsy; and 2 full models that also contained the MEST histologic score, age, medication use, and either racial/ethnic characteristics (white, Japanese, or Chinese) or no racial/ethnic characteristics, to allow application in other ethnic groups. Compared with the clinical model, the full models with and without race/ethnicity had better R2D (26.3% and 25.3%, respectively, vs 20.3%) and AIC (6338 and 6379, respectively, vs 6485), significant increases in C statistic from 0.78 to 0.82 and 0.81, respectively (ΔC, 0.04; 95% CI, 0.03-0.04 and ΔC, 0.03; 95% CI, 0.02-0.03, respectively), and significant improvement in reclassification as assessed by the NRI (0.18; 95% CI, 0.07-0.29 and 0.51; 95% CI, 0.39-0.62, respectively) and IDI (0.07; 95% CI, 0.06-0.08 and 0.06; 95% CI, 0.05-0.06, respectively). External validation was performed in a cohort of 1146 patients. For both full models, the C statistics (0.82; 95% CI, 0.81-0.83 with race/ethnicity; 0.81; 95% CI, 0.80-0.82 without race/ethnicity) and R2D (both 35.3%) were similar or better than in the validation cohort, with excellent calibration.

    Conclusions and Relevance  In this study, the 2 full prediction models were shown to be accurate and validated methods for predicting disease progression and patient risk stratification in IgAN in multi-ethnic cohorts, with additional applications to clinical trial design and biomarker research.

  • 48.
    Barratt, Jonathan
    et al.
    Univ Leicester, Coll Med Biol Sci & Psychol, Leicester, England..
    Lafayette, Richard A.
    Stanford Univ, Dept Med, Div Nephrol, Stanford, CA USA..
    Rovin, Brad H.
    Ohio State Univ, Wexner Med Ctr, Div Nephrol, Columbus, OH USA..
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Budesonide delayed-release capsules to reduce proteinuria in adults with primary immunoglobulin A nephropathy2023In: Expert Review of Clinical Immunology, ISSN 1744-666X, E-ISSN 1744-8409, Vol. 19, no 7, p. 699-710Article in journal (Refereed)
    Abstract [en]

    IntroductionImmunoglobulin A nephropathy (IgAN) is characterized by mesangial deposition of immune complexes containing galactose-deficient IgA1 (Gd-IgA1). This Gd-IgA1 is believed to originate from mucosally sited B cells, which are abundant in the Peyer's patches-rich distal ileum. Nefecon is a targeted-release form of budesonide developed to act in the distal ileum, thereby exerting a direct action on the mucosal tissue implicated in the pathogenesis of the disease.Areas coveredThis review discusses IgAN pathophysiology and provides an overview of the current therapeutic landscape, focusing on Nefecon, the first drug to receive accelerated US approval and conditional EU approval for the treatment of patients with IgAN at risk of rapid disease progression.Expert opinionNefecon trial data thus far have demonstrated a promising efficacy profile, with a predictable pattern of adverse events. Treatment with Nefecon for 9 months reduces proteinuria substantially (Part A of the Phase 3 trial and the Phase 2b trial). A nearly complete prevention of deterioration of renal function has been observed at 12 months in patients at greatest risk of rapid disease progression. Long-term data from Part B of the Phase 3 study will provide 24-month data, furthering understanding of the durability of the 9-month treatment course.

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  • 49.
    Beckmann, Kerri
    et al.
    Univ South Australia, Australian Ctr Precis Hlth, Adelaide, SA, Australia;Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Garmo, Hans
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England;Uppsala Univ Hosp, Reg Canc Ctr Uppsala, Uppsala, Sweden.
    Adolfsson, Jan
    Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.
    Bosco, Cecilia
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Johansson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Robinson, David
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Holmberg, Lars
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Van Hemelrijck, Mieke
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England;Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.
    Androgen Deprivation Therapies and Changes in Comorbidity: A Comparison of Gonadotropin-releasing Hormone Agonists and Antiandrogen Monotherapy as Primary Therapy in Men with High-risk Prostate Cancer2019In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 75, no 4, p. 676-683Article in journal (Refereed)
    Abstract [en]

    Background: Some studies suggest that gonadotropin-releasing hormone (GnRH) agonists are associated with higher risk of adverse events than antiandrogens (AAs) monotherapy. However, it has been unclear whether this is due to indication bias.

    Objective: To investigate rates of change in comorbidity for men on GnRH agonists versus AA monotherapy in a population-based register study.

    Design, setting, and participants: Men with advanced nonmetastatic prostate cancer (PCa) who received primary AA (n = 2078) or GnRH agonists (n = 4878) and age- and area-matched PCa-free men were selected from Prostate Cancer Database Sweden 3.0. Increases in comorbidity were measured using the Charlson Comorbidity Index (CCI), from 5 yr before through to 5 yr after starting androgen deprivation therapy (ADT).

    Outcome measures and statistical methods: Multivariable linear regression was used to determine differences in excess rate of CCI change before and after ADT initiation. Risk of any incremental change in CCI following ADT was assessed using multivariable Cox regression analyses.

    Results and limitations: Men on GnRH agonists experienced a greater difference in excess rate of CCI change after starting ADT than men on AA monotherapy (5.6% per yr, p < 0.001). Risk of any new CCI change after ADT was greater for GnRH agonists than for AA (hazard ratio, 1.32; 95% confidence interval, 1.20-144).

    Conclusions: Impact on comorbidity was lower for men on AA monotherapy than for men on GnRH agonists. Our results should be confirmed through randomised trials of effectiveness and adverse effects, comparing AA monotherapy and GnRH agonists in men with advanced nonmetastatic PCa who are unsuitable for curative treatment.

    Patient summary: Hormone therapies for advanced prostate cancer can increase the risk of other diseases (eg, heart disease, diabetes). This study compared two common forms of hormone therapy and found that the risk of another serious disease was higher for those on gonadotropin-releasing hormone agonists than for those on antiandrogen monotherapy.

  • 50.
    Beckmann, Kerri
    et al.
    Univ South Australia, Allied Hlth & Human Performance, Canc Epidemiol & Populat Hlth Res Grp, Adelaide, SA 5001, Australia; Kings Coll London, Sch Canc & Pharmaceut Studies, Translat Oncol & Urol Res, London SE1 9RT, England.
    Garmo, Hans
    Kings Coll London, Sch Canc & Pharmaceut Studies, Translat Oncol & Urol Res, London SE1 9RT, England; Uppsala Univ Hosp, Reg Canc Ctr, SE-75122 Uppsala, Sweden.
    Franck Lissbrant, Ingela
    Sahlgrenska Univ, Inst Clin Sci, Dept Oncol, SE-41345 Gothenburg, Sweden.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    The Value of Real-World Data in Understanding Prostate Cancer Risk and Improving Clinical Care: Examples from Swedish Registries2021In: Cancers, ISSN 2072-6694, Vol. 13, no 4, article id 875Article, review/survey (Refereed)
    Abstract [en]

    Simple Summary

    Real-world data (RWD), i.e., data reflecting normal clinical practice collected outside the constraints of randomised controlled trials, provide important insights into our understanding of prostate cancer and its management. Clinical cancer registries are an important source of RWD. Depending on their scope and the potential linkage to other data sources, registry-based data can be utilised to address a variety of questions including risk factors, healthcare utilisation, treatment effectiveness, adverse effects, disparities in healthcare access, quality of care and healthcare economics. This review describes the various registry-based RWD sources for prostate cancer research in Sweden (namely the National Prostate Cancer Register, the Prostate Cancer data Base Sweden (PCBaSe) and the Patient-overview Prostate Cancer) and documents their utility for better understanding prostate cancer aetiology and improving clinical care.

    Abstract

    Real-world data (RWD), that is, data from sources other than controlled clinical trials, play an increasingly important role in medical research. The development of quality clinical registers, increasing access to administrative data sources, growing computing power and data linkage capacities have contributed to greater availability of RWD. Evidence derived from RWD increases our understanding of prostate cancer (PCa) aetiology, natural history and effective management. While randomised controlled trials offer the best level of evidence for establishing the efficacy of medical interventions and making causal inferences, studies using RWD offer complementary evidence about the effectiveness, long-term outcomes and safety of interventions in real-world settings. RWD provide the only means of addressing questions about risk factors and exposures that cannot be “controlled”, or when assessing rare outcomes. This review provides examples of the value of RWD for generating evidence about PCa, focusing on studies using data from a quality clinical register, namely the National Prostate Cancer Register (NPCR) Sweden, with longitudinal data on advanced PCa in Patient-overview Prostate Cancer (PPC) and data linkages to other sources in Prostate Cancer data Base Sweden (PCBaSe).

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