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  • 17901.
    Öberg, Kjell E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Is It Time to Widen the Use of Somatostatin Analogs in Neuroendocrine Tumors?2009In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 27, no 28, p. 4635-4636Article in journal (Refereed)
  • 17902.
    Öberg, Kjell E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    The Management of Neuroendocrine Tumours: Current and Future Medical Therapy Options2012In: Clinical Oncology, ISSN 0936-6555, E-ISSN 1433-2981, Vol. 24, no 4, p. 282-293Article in journal (Refereed)
    Abstract [en]

    Neuroendocrine tumours (NETS) are a genetically diverse group of malignancies that sometimes produce peptides causing characteristic hormonal syndromes. NETs can be clinically symptomatic (functioning) or silent (non-functioning); both types frequently synthesise more than one peptide, although often these are not associated with specific syndromes. Based on data from various sources, the incidence and prevalence of NETs is increasing. The primary treatment goal for patients with NETs is curative, with symptom control and the limitation of tumour progression as secondary goals. Surgery is the only possible curative approach and so represents the traditional first-line therapy. However, as most patients with NETs are diagnosed once metastases have occurred, curative surgery is generally not possible. Patients therefore require chronic postoperative medical management with the aim of relieving symptoms and, in recent years, suppressing tumour growth and spread. Somatostatin analogues, such as octreotide long-acting repeatable (LAR), can improve the symptoms of carcinoid syndrome and stabilise tumour growth in many patients. Results from the PROMID study show that octreotide LAR 30 mg is an effective antiproliferative treatment in patients with newly diagnosed, functionally active or inactive, well-differentiated metastatic midgut NETs. An antiproliferative effect can also be achieved with everolimus, and combination therapy with octreotide LAR has shown synergistic antiproliferative activity. In the future, pasireotide, the multi-receptor targeted somatostatin analogue, has the potential to be an effective therapy for de novo or octreotide-refractory carcinoid syndrome and for inhibiting tumour cell proliferation. Peptide receptor radiotherapy with [90]yttrium-DOTATOC or [177]lutetium-DOTATE is also a new interesting treatment option for NETs.

  • 17903.
    Öberg, Kjell E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Tumores Neuroendocrinos Gastrointestinais:  2012In: Aparelho Digestivo Clinica e Cirurgia: Vol. 1 / [ed] Julio Cezar Uili Coelho, Brasil: Atheneu , 2012, 4, p. 337-Chapter in book (Refereed)
  • 17904.
    Öberg, Kjell E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Reubi, Jean-Claude
    Kwekkeboom, Dik J.
    Krenning, Eric P.
    Role of somatostatins in gastroenteropancreatic neuroendocrine tumor development and therapy2010In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 139, no 3, p. 742-753, 753.e1Article, review/survey (Refereed)
    Abstract [en]

    The incidence and prevalence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have increased in the past 20 years. GEP-NETs are heterogeneous tumors, in terms of clinical and biological features, that originate from the pancreas or the intestinal tract. Some GEP-NETs grow very slowly, some grow rapidly and do not cause symptoms, and others cause hormone hypersecretion and associated symptoms. Most GEP-NETs overexpress receptors for somatostatins. Somatostatins inhibit the release of many hormones and other secretory proteins; their effects are mediated by G protein-coupled receptors that are expressed in a tissue-specific manner. Most GEP-NETs overexpress the somatostatin receptor SSTR2; somatostatin analogues are the best therapeutic option for functional neuroendocrine tumors because they reduce hormone-related symptoms and also have antitumor effects. Long-acting formulations of somatostatin analogues stabilize tumor growth over long periods. The development of radioactive analogues for imaging and peptide receptor radiotherapy has improved the management of GEP-NETs. Peptide receptor radiotherapy has significant antitumor effects, increasing overall survival times of patients with tumors that express a high density of SSTRs, particularly SSTR2 and SSTR5. The multi-receptor somatostatin analogue SOM230 (pasireotide) and chimeric molecules that bind SSTR2 and the dopamine receptor D2 are also being developed to treat patients with GEP-NETs. Combinations of radioactive labeled and unlabeled somatostatin analogues and therapeutics that inhibit other signaling pathways, such as mammalian target of rapamycin (mTOR) and vascular endothelial growth factor, might be the most effective therapeutics for GEP-NETs.

  • 17905.
    Öberg, Kjell
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Eriksson, Barbro
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Carcinoid Syndrome2005In: Endocrinology, Elsevier , 2005Chapter in book (Refereed)
  • 17906.
    Öberg, Kjell
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Eriksson, BarbroUppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Neuroendocrine tumours: Preface2007Collection (editor) (Other scientific)
  • 17907.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nuclear medicine in the detection, staging and treatment of gastrointestinal carcinoid tumours2005In: Best Practice & Research Clinical Endocrinology & Metabolism, ISSN 1521-690X, Vol. 19, no 2, p. 265-276Article in journal (Refereed)
    Abstract [en]

    Carcinoid tumours belong to the family of neuroendocrine tumours with a capacity to take up and concentrate amines and precursors as well as peptides, and can thereby be detected by nuclear medicine techniques. These rare tumours are difficult to diagnose at earlier stages because of small size and multiplicity. Computed tomography (CT) and magnetic resonance imaging (MRI) are mostly of benefit for detection of larger primary tumours (1–3cm) and liver and lymph-node metastases. A majority of carcinoid tumours express somatostatin receptors, particularly receptor type 2, and thus somatostatin receptor scintigraphy (SRS) can be used for detection and staging of carcinoid tumours. The detection rate of carcinoid tumours has been reported to be somewhere between 80 and 100% in different studies. The scintigraphy gives a good staging of the disease and detection of unexpected tumour sites, which were not determined by conventional imaging. This method also indicates content of somatostatin receptors, which might indicate efficacy of treatment with octreotide or other somatostatin analogues. Another new non-invasive technique for detection of carcinoid tumours is positron emission tomography (PET). The biological substance for study can be labelled for radioactive imaging with radionuclears, such as 11C, 15O and 18F, with emission of positrons. More than 95% of patients studied displayed high tracer uptake from PET with 11C-5HTP (5-hydroxytryptophan), which is significantly higher compared to both computer tomography and somatostatin receptor scintigraphy. MIBG has been used for decades to visualize carcinoid tumours, because MIBG is concentrated in the endocrine cells. It was initially developed to detect phaeochromocytomas of the adrenal with reported high sensitivity (87%) and specificity as high as 99%. The method can be used when other methods fail to localize carcinoid tumours and particularly when treatment with 131I-MIBG is being considered.

    Tumour-targeted treatment for malignant carcinoid tumour is still investigational, but has become of significant interest with the use of radiolabelled somatostatin analogues. Since a majority of carcinoid tumours present somatostatin receptors and can therefore be visualized in vivo by using radiolabelled somatostatin analogues, it seems logical to try to target these tumours with radioactive substances, not only for visualization but also for treatment.

    111Indium-DTPA-octreotide has been used as the first tumour-targeted treatment, with rather low response rates (in the order of 10–20%) and no significant tumour shrinkage. The second radioactive analogue which has been applied in the clinic is 90yttrium-DOTA-Tyr3-octreotide, which has given partial and complete remissions in 20–30% of patients. The most significant side-effects have been kidney dysfunction, thrombocytopenia and liver toxicity. The most recent compound is 177lutetium-DOTA-Tyr3-octreotate, which has been applied by the Rotterdam group and has been reported to give partial remission in about 40% of the patients. In the near future, combined treatment with both 90yttrium and 177lutetium coupled to a somatostatin analogue might come into clinical trials. 177Lutetium may be more effective for smaller tumours whereas 90yttrium may be more effective for larger tumours.

  • 17908.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    The role of interferons in the management of carcinoid tumors1991In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 30, no 4, p. 519-522Article in journal (Refereed)
    Abstract [en]

    Malignant carcinoid tumors with the carcinoid syndrome has over the years presented a therapeutic challenge. Surgery is the treatment of choice in local disease but when liver metastases have developed other treatment procedures must be considered. Conventional chemotherapy has been of little benefit, whereas a new somatostatin analogue octreotide gives a good control of clinical symptoms but not of tumor progression. Interferon treatment was introduced in 1982 by our group and we are now presenting results of medical treatment in 130 patients with histologically verified malignant carcinoid tumors and liver metastases. One hundred and eleven patients were treated with alpha-interferon, whereas 19 patients received conventional chemotherapy. Forty-seven out of 111 patients (42%) treated with alpha-interferon demonstrated a significant biochemical response and 15% also more than 50% reduction of tumor size. In another 43 (39%) patients stabilization of the carcinoid disease was noted whereas 21 (19%) showed progressive disease. The median duration of response was 34 months. Subjective response with improvement of diarrheas, flush and/or bronchoconstriction was noticed in 76 patients (68%). Among the 19 patients treated with conventional chemotherapy only 2 showed biochemical response and it lasted only for 3-5 months. The patients treated with chemotherapy had a median survival of only 8 months compared with 80+ months in the group treated with alpha-interferon. The adverse reactions of alpha-interferon are manageable and consist mainly of fatigue, weight reduction and reduction of blood cell counts. Neutralizing interferon antibodies might occur in patients treated with recombinant alpha-interferons (5-15%).

  • 17909.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Interferon alone or in combination with chemotherapy1994In: Digestion, ISSN 0012-2823, E-ISSN 1421-9867, Vol. 55, p. 64-69Article in journal (Refereed)
  • 17910.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ferone, Diego
    Kaltsas, Gregory
    Knigge, Ulrich-Peter
    Taal, Babs
    Plöckinger, Ursula
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: biotherapy2009In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 90, no 2, p. 209-213Article in journal (Refereed)
  • 17911.
    Öberg, Kjell
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Goldhirsch, A
    Munro Neville, A
    Neoplastic disorders of the adrenal glands1999In: Textbook of uncommon cancer. Second edition, 1999, Vol. 17, p. 239-Chapter in book (Other scientific)
  • 17912.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Ferolla, P.
    Papotti, M.
    Neuroendocrine bronchial and thymic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up2012In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, no suppl. 7, p. vii120-vii123Article in journal (Refereed)
  • 17913.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Kwekkeboom, D.
    Jelic, S.
    Neuroendocrine bronchial and thymic tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up2010In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 21, no Suppl 5, p. v220-v222Article in journal (Refereed)
    Abstract [en]

    The annual incidence of lung neuroendocrine tumour has been reported to be 1.35/100 000/year and the overall age adjusted incidence for thymic carcinoid 0.02/100 000/year. Of all neuroendocrine tumours, ∼25% are located in the respiratory tract. Both bronchial and thymic carcinoids may be part of multiple endocrine neoplasia type 1 syndrome (MEN-I) (5%–15%). The median age at diagnosis for lung neuroendocrine tumours is 64 years and for thymic tumours 59 years.

  • 17914.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jelic, S
    Neuroendocrine bronchial and thymic tumors: ESMO clinical recommendation for diagnosis, treatment and follow-up2008In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 19, no Suppl. 2, p. 102-103Article in journal (Refereed)
  • 17915.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Jelic, S.
    Neuroendocrine bronchial and thymic tumors: ESMO clinical recommendation for diagnosis, treatment and follow-up2009In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 20, no Suppl 4, p. 147-149Article in journal (Refereed)
  • 17916.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Jelic, S.
    Neuroendocrine gastroenteropancreatic tumors: ESMO clinical recommendation for diagnosis, treatment and follow-up2009In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 20, no Suppl 4, p. 150-153Article in journal (Refereed)
  • 17917.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jelic, S
    Neuroendocrine gastroenteropancreatic tumors: ESMO clinical recommendations for diagnosis, treatment and follow-up.2008In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 19, no Suppl. 2, p. 104-105Article in journal (Refereed)
  • 17918.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Knigge, U.
    Kwekkeboom, D.
    Perren, A.
    Neuroendocrine gastro-entero-pancreatic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up2012In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, no suppl. 7, p. vii124-vii130Article in journal (Refereed)
  • 17919.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Krenning, Eric
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bodei, Lisa
    Kidd, Mark
    Tesselaar, Margot
    Ambrosini, Valentina
    Baum, Richard P
    Kulke, Matthew
    Pavel, Marianne
    Cwikla, Jaroslaw
    Drozdov, Ignat
    Falconi, Massimo
    Fazio, Nicola
    Frilling, Andrea
    Jensen, Robert
    Koopmans, Klaus
    Korse, Tiny
    Kwekkeboom, Dik
    Maecke, Helmut
    Paganelli, Giovanni
    Salazar, Ramon
    Severi, Stefano
    Strosberg, Jonathan
    Prasad, Vikas
    Scarpa, Aldo
    Grossman, Ashley
    Walenkamp, Annemeik
    Cives, Mauro
    Virgolini, Irene
    Kjaer, Andreas
    Modlin, Irvin M
    A Delphic consensus assessment: imaging and biomarkers in gastroenteropancreatic neuroendocrine tumor disease management2016In: Endocrine Connections, E-ISSN 2049-3614, Vol. 5, no 5, p. 174-187Article in journal (Refereed)
    Abstract [en]

    The complexity of the clinical management of neuroendocrine neoplasia (NEN) is exacerbated by limitations in imaging modalities and a paucity of clinically useful biomarkers. Limitations in currently available imaging modalities reflect difficulties in measuring an intrinsically indolent disease, resolution inadequacies and inter-/intra-facility device variability and that RECIST (Response Evaluation Criteria in Solid Tumors) criteria are not optimal for NEN. Limitations of currently used biomarkers are that they are secretory biomarkers (chromogranin A, serotonin, neuron-specific enolase and pancreastatin); monoanalyte measurements; and lack sensitivity, specificity and predictive capacity. None of them meet the NIH metrics for clinical usage. A multinational, multidisciplinary Delphi consensus meeting of NEN experts (n = 33) assessed current imaging strategies and biomarkers in NEN management. Consensus (>75%) was achieved for 78% of the 142 questions. The panel concluded that morphological imaging has a diagnostic value. However, both imaging and current single-analyte biomarkers exhibit substantial limitations in measuring the disease status and predicting the therapeutic efficacy. RECIST remains suboptimal as a metric. A critical unmet need is the development of a clinico-biological tool to provide enhanced information regarding precise disease status and treatment response. The group considered that circulating RNA was better than current general NEN biomarkers and preliminary clinical data were considered promising. It was resolved that circulating multianalyte mRNA (NETest) had clinical utility in both diagnosis and monitoring disease status and therapeutic efficacy. Overall, it was concluded that a combination of tumor spatial and functional imaging with circulating transcripts (mRNA) would represent the future strategy for real-time monitoring of disease progress and therapeutic efficacy.

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  • 17920.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kulke, M.
    Pavel, M.
    Phan, A.
    Hoosen, S.
    St Peter, J.
    Cherfi, A.
    Yao, J. C.
    PROGNOSTIC AND PREDICTIVE VALUE OF CHROMOGRANIN A AND NEURON-SPECIFIC ENOLASE IN PATIENTS (PTS) WITH ADVANCED PANCREATIC NEUROENDOCRINE TUMORS (PNET) TREATED WITH EVEROLIMUS2010In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 21, p. 266-266Article in journal (Other academic)
  • 17921.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Lamberts, Steven W. J.
    Erasmus MC, Rotterdam, Netherlands..
    Somatostatin analogues in acromegaly and gastroenteropancreatic neuroendocrine tumours: past, present and future2016In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 23, no 12, p. R551-R566Article, review/survey (Refereed)
    Abstract [en]

    Acromegaly is a hormonal disorder that arises when the pituitary gland secretes excess growth hormone (GH), which in turn stimulates a concomitant increase in serum insulin-like growth factor 1 (IGF-1) levels. Gastroenteropancreatic neuroendocrine tumours (GEP-NET) constitute a heterogeneous group of tumours that can secrete serotonin and a variety of peptide hormones that may cause characteristic symptoms known as carcinoid syndrome or other symptoms and hormonal hypersecretion syndromes depending on the tumour's site of origin. Current medical therapy for the treatment of acromegaly and GEP-NET involves the administration of somatostatin analogues that effectively suppress excess hormone secretion. After its discovery in 1979, octreotide became the first synthetic biologically stable somatostatin analogue with a short-acting formulation of octreotide introduced into clinical practice in the late 1980s. Lanreotide, another somatostatin analogue, became available in the mid-1990s initially as a prolonged-release formulation administered every 10 or 14 days. Long-acting release formulations of both octreotide (Sandostatin LAR and Novartis) and lanreotide (Somatuline Autogel, Ipsen), based on microparticle and nanoparticle drug-delivery technologies, respectively, were later developed, which allowed for once-monthly administration and improved convenience. First-generation somatostatin analogues remain one of the cornerstones of medical therapy in the management of pituitary and GEP-NET hormone hypersecretion, with octreotide having the longest established efficacy and safety profile of the somatostatin analogue class. More recently, pasireotide (Signifor), a next-generation multireceptor-targeted somatostatin analogue, has emerged as an alternative therapeutic option for the treatment of acromegaly. This review summarizes the development and clinical success of somatostatin analogues.

  • 17922.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Metz, David C
    University of Pennsylvania School of Medicine, USA.
    Chapter 6, Diagnostic pathways:  2010In: Handbook of Gastroenteropancreatic and thoracic neuroendocrine tumours / [ed] Martyn Caplin & James C Yao, Bioscientifica, 2010Chapter in book (Other academic)
  • 17923.
    Öberg, Kjell
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Endokrin onkologi.
    Modlin, Irvin M
    Non-functioning pancreatic endocrine tumors2007In: A Century of Advances in Neuroendocrine tumor biology and treatment, Felsenstein , 2007, p. 86-99Chapter in book (Refereed)
  • 17924.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Modlin, Irvin M.
    Yale Univ, Sch Med, New Haven, CT 06510 USA..
    De Herder, Wouter
    Erasmus MC, Endocrinol Sect, Dept Internal Med, Rotterdam, Netherlands..
    Pavel, Marianne
    Charite, D-13353 Berlin, Germany..
    Klimstra, David
    Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA..
    Frilling, Andrea
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Metz, David C.
    Univ Penn Hlth Syst, Div Gastroenterol, Philadelphia, PA USA..
    Heaney, Anthony
    Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA..
    Kwekkeboom, Dik
    Erasmus MC, Dept Nucl Med, Rotterdam, Netherlands..
    Strosberg, Jonathan
    H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA..
    Meyer, Timothy
    UCL, Inst Canc, London, England..
    Moss, Steven F.
    Brown Univ, Liver Res Ctr, Providence, RI 02912 USA..
    Washington, Kay
    Vanderbilt Univ, Dept Pathol, Med Ctr, Nashville, TN 37235 USA..
    Wolin, Edward
    Univ Kentucky, Markey Canc Ctr, Lexington, KY USA..
    Liu, Eric
    Vanderbilt Univ, Dept Surg, Med Ctr, Nashville, TN 37235 USA..
    Goldenring, James
    Vanderbilt Univ, Dept Cell & Dev Biol, Med Ctr, Nashville, TN 37235 USA..
    Consensus on biomarkers for neuroendocrine tumour disease2015In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 16, no 9, p. E435-E446Article, review/survey (Refereed)
    Abstract [en]

    Management of neuroendocrine neoplasia represents a clinical challenge because of its late presentation, lack of treatment options, and limitations in present imaging modalities and biomarkers to guide management. Monoanalyte biomarkers have poor sensitivity, specificity, and predictive ability. A National Cancer Institute summit, held in 2007, on neuroendocrine tumours noted biomarker limitations to be a crucial unmet need in the management of neuroendocrine tumours. A multinational consensus meeting of multidisciplinary experts in neuroendocrine tumours assessed the use of current biomarkers and defined the perquisites for novel biomarkers via the Delphi method. Consensus (at > 75%) was achieved for 88 (82%) of 107 assessment questions. The panel concluded that circulating multianalyte biomarkers provide the highest sensitivity and specifi city necessary for minimum disease detection and that this type of biomarker had sufficient information to predict treatment effectiveness and prognosis. The panel also concluded that no monoanalyte biomarker of neuroendocrine tumours has yet fulfilled these criteria and there is insufficient information to support the clinical use of miRNA or circulating tumour cells as useful prognostic markers for this disease. The panel considered that trials measuring multianalytes (eg, neuroendocrine gene transcripts) should also identify how such information can optimise the management of patients with neuroendocrine tumours.

  • 17925.
    Öberg, Kjell
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Endokrin onkologi.
    Rehfeld, J
    Summation Session Section II: Neuroendocrine cell biology2007In: A Century of Advances in Neuroendocrine tumor biology and treatment, 2007Chapter in book (Refereed)
  • 17926.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Imaging of Neuroendocrine Tumors2016In: Imaging in Endocrine Disorders / [ed] M Buchfelder, F Guaraldi, E Ghigo, F Guaraldi, A Benso, Basel: S. Karger, 2016, p. 142-151Chapter in book (Refereed)
  • 17927.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Imaging of Neuroendocrine Tumors2016In: Imaging in Endocrine Disorders / [ed] Buchfelder M., Guaraldi F., Basel: Karger , 2016, Vol. 45, p. 142-151Chapter in book (Refereed)
    Abstract [en]

    Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies with a very variable clinical expression and progression. They present unique properties that are important to consider for radiological and nuclear imaging, such as APUD-characteristics (amine precursor uptake and dearboxylation), as well as the expression of somatostatin receptors. The most common localizations are the lungs, gastrointestinal tract and pancreas. The only curative treatment is surgery, but more than 50% present metastatic disease at the time of diagnosis. The systemic treatment includes chemotherapy and targeted agents, as well as peptide receptor radiotherapy. The diagnosis and follow-up of these tumors necessitate a large number of different imaging methods, such as CT, MRI, US, SRS and PET. Ultrasonography offers the possibility to take guided biopsies from different lesions. Somatostatin receptor scintigraphy was developed in the 1990s and nowadays presents the standard of care for NETs in most countries. The procedure offers a total body examination and a better staging of the disease. However, it has been replaced in most centers by PET/CT with 68Ga-DOTA-somatostatin analogues with a superior spatial resolution and faster imaging (one-stop procedure). Another tracer used for PET/CT is 18FDG, particularly for high-grade tumors. Other more specific tracers are 18F-L-DOPA, 11C-L-DOPA and 11C-5-hydroxytryptophan, which have demonstrated excellent imaging results. The new targeted agents present a challenge in the evaluation procedure of treatment and, therefore, new imaging techniques and an improvement of currently available techniques are mandatory.

  • 17928.
    Öberg, Kjell
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Tiensuu Janson, Eva
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Diseases of the gut and liver: The carcinoid syndrome2005In: Clinical Gastroenterology and Hepatology: Chapter 110, Elsevier Mosby , 2005, p. 823-Chapter in book (Refereed)
  • 17929.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Yao, J. C.
    Rationale for Combining mTOR with other Targeted Agents in the Treatment of Neuroendocrine Tumors2010In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 92, no 1, p. 49-50Article in journal (Other academic)
  • 17930.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Rindi, G.
    Jelic, S.
    Neuroendocrine gastroenteropancreatic tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up2010In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 21, no Suppl 5, p. v223-v227Article in journal (Refereed)
  • 17931.
    Ödling, Maria
    et al.
    Karolinska Inst, Dept Clin Sci & Educ, Södersjukhuset, Stockholm, Sweden.
    Andersson, Niklas
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Hallberg, Jenny
    Karolinska Inst, Dept Clin Sci & Educ, Södersjukhuset, Stockholm, Sweden; Sachs Children & Youth Hosp, Stockholm, Sweden.
    Almqvist, Catarina
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden; Karolinska Univ Hosp, Paediat Allergy & Pulmonol Unit, Astrid Lindgrens Childrens Hosp, Stockholm, Sweden.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Bergström, Anna
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden; Reg Stockholm, Ctr Occupat & Environm Med, Stockholm, Sweden.
    Melén, Erik
    Karolinska Inst, Dept Clin Sci & Educ, Södersjukhuset, Stockholm, Sweden; Karolinska Inst, Inst Environm Med, Stockholm, Sweden; Sachs Children & Youth Hosp, Stockholm, Sweden.
    Kull, Inger
    Karolinska Inst, Dept Clin Sci & Educ, Södersjukhuset, Stockholm, Sweden; Sachs Children & Youth Hosp, Stockholm, Sweden.
    A Gap Between Asthma Guidelines and Management for Adolescents and Young Adults2020In: Journal of Allergy and Clinical Immunology: In Practice, ISSN 2213-2198, E-ISSN 2213-2201, Vol. 8, no 9, p. 3056-3065.e2Article in journal (Refereed)
    Abstract [en]

    Background

    For adolescents, asthma management can be challenging during the transition to adulthood, and changes in health care and pharmacological treatment may occur.

    Objective

    To investigate asthma-related health care consumption and pharmacological dispensation during the transition process.

    Methods

    In a Swedish birth cohort study, questionnaire and clinical data from the 16- and 24-year follow-ups were linked to national and regional registries for asthma-related health care consumption and dispensed medications during an 8-year period: 4 years before and after age 18 y, respectively.

    Results

    In the study population (n = 1808), 14% fulfilled the study definition of current asthma at the 16- and 24-year follow-up and 8% (n = 147) had persistent asthma. Among them, register data showed that in the 4-year period before their 18th birthday, 39% (58 of 147) had at least 1 consultation, similar to 37% (55 of 147) in the following 4-year period. The mean number of consultations before age 18 years was 1.6, compared with 1.0 after age 18 years (P = .02). At least 1 dispensation of any inhaled corticosteroid before age 18 years was found for 73% (107 of 147), compared with 50% (74 of 147) after age 18 years. The mean number of dispensed any inhaled corticosteroid was 3.1 before 18 years and 2.1 after 18 years (P < .01). Only 3% (5 of 147) had a regular dispensation of any inhaled corticosteroid once a year during the 8-year period.

    Conclusions

    Health care consultations were fewer than recommended in guidelines and decreased after the transition to adult health care. Almost no one had dispensed regular asthma medications during the 8-year period.

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  • 17932.
    Ödling, Maria
    et al.
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden..
    Andersson, Niklas
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Melén, Erik
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.;Karolinska Inst, Inst Environm Med, Stockholm, Sweden.;SachsChildren & Youth Hosp, Stockholm, Sweden..
    Bergström, Anna
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.;Ctr Occupat & Environm Med Reg Stockholm, Stockholm, Sweden..
    Kull, Inger
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.;SachsChildren & Youth Hosp, Stockholm, Sweden..
    Health-related quality of life decreases in young people with asthma during the transition from adolescence to young adulthood: a birth cohort study2023In: BMC Pulmonary Medicine, E-ISSN 1471-2466, Vol. 23, article id 34Article in journal (Refereed)
    Abstract [en]

    Background: During the transition from paediatric to adult healthcare there is a gap between asthma guidelines and actual management with decreased healthcare consultations and dispensations of asthma medications after the transition to adult healthcare among young people with asthma. How health-related quality of life (HRQoL) develops during the transition from adolescence to young adulthood is unclear. Our aim was therefore to investigate HRQoL among young people with asthma during the transition to adulthood. Further, to assess if level of asthma control and physical activity influence any potential association between asthma and HRQoL.

    Methods: The study population consisted of 2268 participants from the ongoing Swedish population-based prospective birth cohort BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology). HRQoL was measured using the instrument EQ-5D-3 L and three general questions. The EQ-5D-3 L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3 L instrument and questions on general health, symptoms and treatment of asthma, and lifestyle factors were based on data from follow-ups at 16 and 24 years. Cross-sectional analyses were made.

    Results: At the 24-year follow-up, the adjusted median values of EQ VAS were lower compared with at the 16-year follow-up; among both participants with asthma (80 vs. 85, p < 0.01) and those without asthma (80 vs. 87, p < 0.01). At the 24-year follow-up, participants with uncontrolled asthma had a lower adjusted median EQ VAS score than peers with controlled/partly controlled asthma (75 vs. 80, p = 0.03). Further, young adults with asthma who did not fulfil the WHO recommendations on physical activity had lower EQ VAS scores than peers who did (70 vs. 80, p < 0.01).

    Conclusion: HRQoL is lower in young adulthood than in adolescence. Young adults with asthma having uncontrolled disease or who are physically inactive appear to be particularly vulnerable.

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  • 17933.
    Ödling, Maria
    et al.
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
    Jonsson, Marina
    Centre for Occupationaland Environmental Medicine, Stockholm County Council, Stockholm, Sweden.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Melén, Erik
    Institute of Environmental Medicine, Karolinska Institutet, Solna, Sweden; Sachs’ Children and Youth Hospital, Stockholm, Sweden.
    Bergström, Anna
    Centre for Occupationaland Environmental Medicine, Stockholm County Council, Stockholm, Sweden; Institute of Environmental Medicine, Karolinska Institutet, Solna, Sweden.
    Kull, Inger
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Sachs’ Children and Youth Hospital, Stockholm, Sweden.
    Lost in the transition from pediatric to adult healthcare? Experiences of young adults with severe asthma2020In: Journal of Asthma, ISSN 0277-0903, E-ISSN 1532-4303, Vol. 57, no 10, p. 1119-1127Article in journal (Refereed)
    Abstract [en]

    Objective: Asthma is a multifaceted disease, and severe asthma is likely to be persistent. Patients with severe asthma have the greatest burden and require more healthcare resources than those with mild-to-moderate asthma. The majority with asthma can be managed in primary care, while some patients with severe asthma warrant referral for expert advice regarding management. In adolescence, this involves a transition from pediatric to adult healthcare. This study aimed to explore how young adults with severe asthma experienced the transition process.Methods: Young adults with severe asthma were recruited from an ongoing Swedish population-based cohort. Qualitative data were obtained through individual interviews (n = 16, mean age 23.4 years), and the transcribed data were analyzed with systematic text condensation.Results: Four categories emerged based on the young adults' experiences: "I have to take responsibility", "A need of being involved", "Feeling left out of the system", and "Lack of engagement". The young adults felt they had to take more responsibility, did not know where to turn, and experienced fewer follow-ups in adult healthcare. Further, they wanted healthcare providers to involve them in self-management during adolescence, and in general, they felt that their asthma received insufficient support from healthcare providers.Conclusions: Based on how the young adults with severe asthma experienced the transition from pediatric to adult healthcare, it is suggested that healthcare providers together with each patient prepare, plan, and communicate in the transition process for continued care in line with transition guidelines.

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  • 17934. Ödling, Maria
    et al.
    Wang, Gang
    Andersson, Niklas
    Hallberg, Jenny
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Bergström, Anna
    Melén, Erik
    Kull, Inger
    Characterization of Asthma Trajectories from Infancy to Young Adulthood2021In: Journal of Allergy and Clinical Immunology: In Practice, ISSN 2213-2198, E-ISSN 2213-2201, Vol. 9, no 6, p. 2368-2376.e3Article in journal (Refereed)
    Abstract [en]

    Background: Development of asthma is complicated by the multidimensional nature of the disease.

    Objective: To identify and characterize trajectories of asthma from infancy to young adulthood, and their associations with lung function and inflammatory and respiratory markers in adolescence and young adulthood.

    Methods: A latent class analysis was performed in a population-based cohort (N = 4089). Parental and self-reported symptoms of asthma were used to investigate asthma development. We characterized background factors, allergic comorbidity, and IgE sensitization and investigated associations with asthma markers.

    Rerults: A 4-class solution of asthma trajectories was identified: never/infrequent (n = 3291 [80.4%]), early-onset transient (n = 307 [7.5%]), adolescent-onset (n = 261 [6.4%]), and persistent asthma (n = 230 [5.6%]). Uncontrolled asthma was equally prevalent in the adolescent-onset and persistent asthma trajectory groups, at both age 16 (41.7% vs 42.4%; P = .90) and 24 years (53.7% vs 52.4%; P = .81). The persistent asthma trajectory group had a higher proportion of eosinophil counts greater than or equal to 0.3 (109 cells/L) at age 24 years compared with the adolescent-onset trajectory group (31.0% vs 18.5%; P < .01).

    Conclusions: The adolescent-onset and persistent asthma trajectory groups had equal burdens of asthma control in adolescence and young adulthood. However, the persistent asthma trajectory group showed more signs of type 2 inflammation than the adolescent-onset trajectory group. This unbiased approach highlights the need of identifying patients with adolescent asthma to optimize care, because they suffer the same lack of asthma control as those with persistent asthma.

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  • 17935.
    Ödman, Jesper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jonasson, Rasmus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Patienters tillfredsställelse av smärtlindring vid akut smärta inom akutsjukvård: En litteraturstudie2021Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: One of the most common reasons for patients visiting emergency care units are due to acute pain of some sort both nationally and internationally. It’s therefore of great importance that these patients are offered an adequate treatment for their pain, if not this could lead to acute and chronic discomfort, unnecessary suffering both in a short and a long time perspective and ultimately even to distrust in the emergency healthcare system.

    Aim: To investigate the literature on patients’ satisfaction with pain management provided by emergency care.Method: A literature review with an inductive approach. A total of 14 articles from the PubMed and CINAHL databases are included and are presented through a thematic analysis.

    Results: Three themes were identified after the analysis of the included articles. These consist of factors that affect satisfaction, factors that increase the effectiveness of management and affect satisfaction and experiences towards treatment that affect satisfaction. The compassion from caregivers, the fact that patients received analgesics and in good time are all factors that contributed to increased satisfaction among patients. Different pain protocols and fears/worries that patients may have were also factors that contributed to how satisfied the patients felt about the management of their acute pain in the emergency care setting.

    Conclusion: Key factors when it comes to satisfactory treatment of patients in acute pain are: receiving analgesia, receiving analgesia on time and the establishment of a relationship based on trust between patient and caregiver.

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  • 17936. Ögmundsdottir Michelsen, Halldora
    et al.
    Henriksson, Peter
    Wallert, John
    Bäck, Maria
    Sjölin, Ingela
    Schlyter, Mona
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Kiessling, Anna
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hag, Emma
    Nilsson, Lennart
    Schiopu, Alexandru
    Zaman, M. Justin
    Leosdottir, Margret
    Organizational and patient-level predictors for attaining key risk factor targets in cardiac rehabilitation after myocardial infarction: The Perfect-CR study2023In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 371, p. 40-48Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Benefits of cardiac rehabilitation (CR) programme components on attaining risk factor targets post-myocardial infarction (MI) and their predictive strength relative to patient characteristics remain unclear. We aimed to identify organizational and patient-level predictors of risk factor target attainment at one-year post-MI.

    METHODS: In this observational study data on CR organization at 78 Swedish CR centres was collected and merged with patient-level registry data (n = 7549). Orthogonal partial least squares discriminant analysis identified predictors (Variables of Importance for the Projection (VIP) values >0.8) of attaining low-density lipoprotein-cholesterol (LDL-C) <1.8 mmol/L, blood pressure (BP) <140/90 mmHg and smoking abstinence.

    RESULTS: The strongest predictors (VIP [95% CI]) for attaining LDL-C and BP targets were offering psychosocial management (2.14 [1.78-2.50]; 2.45 [1.91-2.99]), having a psychologist in the CR team (1.62 [1.36-1.87]; 2.05 [1.67-2.44]), extended opening hours (2.13 [2.00-2.27]; 1.50 [0.91-2.10]), adequate facilities (1.54 [0.91-2.18]; 1.89 [1.38-2.40]), and having a medical director (1.70 [0.91-2.48]; 1.46 [1.04-1.88]). The strongest patient-level predictors of attaining LDL-C and/or BP targets were low baseline LDL-C (3.95 [3.39-4.51]) and having no history of hypertension (2.93 [2.60-3.26]), respectively, followed by exercise-based CR participation (1.38 [0.66-2.10]; 1.46 [1.14-1.78]). For smoking abstinence, the strongest organizational predictor was varenicline being prescribed by CR physicians (1.88 [0.95-2.80]) and patient-level predictors were participation in exercise-based CR (2.47 [2.07-2.88]) and group education (1.92 [1.43-2-42]), and no cardiovascular disease history (2.13 [1.78-2.48]).

    CONCLUSIONS: We identified multiple CR organizational and patient-level predictors of attaining risk factor targets post-MI. These results may influence the future design of comprehensive CR programmes.

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  • 17937.
    Ögmundsdottir Michelsen, Halldora
    et al.
    Department of Cardiology , Skane University Hospital and Department of Clinical Sciences, Lund University, Malmö, Sweden..
    Sjölin, Ingela
    Department of Cardiology , Skane University Hospital and Department of Clinical Sciences, Lund University, Malmö, Sweden..
    Schlyter, Mona
    Department of Cardiology , Skane University Hospital and Department of Clinical Sciences, Lund University, Malmö, Sweden..
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Kiessling, Anna
    Department of Clinical Sciences Danderyd Hospital , Karolinska Institute, Stockholm, Sweden..
    Henriksson, Peter
    Department of Clinical Sciences Danderyd Hospital , Karolinska Institute, Stockholm, Sweden..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hag, Emma
    Department of Internal Medicine , County Hospital Ryhov, Jönköping, Sweden..
    Nilsson, Lennart
    Department of Medical and Health Sciences , Linköping University, Sweden..
    Bäck, Maria
    Department of Occupational Therapy and Physiotherapy , Sahlgrenska University Hospital, Gothenburg, Sweden.; Department of Medical and Health Sciences , Division of Physiotherapy, Linköping University, Sweden..
    Schiopu, Alexandru
    Department of Cardiology , Skane University Hospital and Department of Clinical Sciences, Lund University, Malmö, Sweden..
    Zaman, M Justin
    Department of Cardiology , James Paget University Hospital, Gorleston-on-Sea, Great Yarmouth, Norfolk, UK..
    Leosdottir, Margret
    Department of Cardiology , Skane University Hospital and Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Cardiac rehabilitation after acute myocardial infarction in Sweden: evaluation of programme characteristics and adherence to European guidelines: The Perfect Cardiac Rehabilitation (Perfect-CR) study2020In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 27, no 1, p. 18-27Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: While patient performance after participating in cardiac rehabilitation programmes after acute myocardial infarction is regularly reported through registry and survey data, information on cardiac rehabilitation programme characteristics is less well described.

    AIM: The aim of this study was to evaluate Swedish cardiac rehabilitation programme characteristics and adherence to European Guidelines on Cardiovascular Disease Prevention.

    METHOD: Cardiac rehabilitation programme characteristics at all 78 cardiac rehabilitation centres in Sweden in 2016 were surveyed using a web-based questionnaire (100% response rate). The questions were based on core components of cardiac rehabilitation as recommended by European Guidelines.

    RESULTS: There was a wide variation in programme duration (2-14 months). All programmes reported offering an individual post-discharge visit with a nurse, and 90% (n = 70) did so within three weeks from discharge. Most programmes offered centre-based exercise training (n = 76, 97%) and group educational sessions (n = 61, 78%). All programmes reported to the national audit, SWEDEHEART, and 60% (n = 47) reported that performance was regularly assessed using audit data, to improve quality of care. Ninety-six per cent (n = 75) had a core team consisting of a cardiologist, a physiotherapist and a nurse and 76% (n = 59) reported having a medical director. Having other allied healthcare professionals included in the cardiac rehabilitation team varied. Forty per cent (n = 31) reported having regular team meetings where nurses, physiotherapists and cardiologist could discuss patient cases.

    CONCLUSION: The overall quality of cardiac rehabilitation programmes provided in Sweden is high. Still, there are several areas of potential improvement. Monitoring programme characteristics as well as patient outcomes might improve programme quality and patient outcomes both at a local and a national level.

  • 17938. Ögmundsdóttir Michelsen, Halldóra
    et al.
    Lidin, Matthias
    Bäck, Maria
    Scott Duncan, Therese
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Participatory eHealth and Health Data Research Group.
    Ekman, Björn
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Hägglund, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Participatory eHealth and Health Data Research Group.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Schlyter, Mona
    Leósdóttir, Margrét
    The effect of audit and feedback and implementation support on guideline adherence and patient outcomes in cardiac rehabilitation: a study protocol for an open-label cluster-randomized effectiveness-implementation hybrid trial2024In: Implementation Science, E-ISSN 1748-5908, Vol. 19, no 1, article id 35Article in journal (Refereed)
    Abstract [en]

    Background

    Providing secondary prevention through structured and comprehensive cardiac rehabilitation programmes to patients after a myocardial infarction (MI) reduces mortality and morbidity and improves health-related quality of life. Cardiac rehabilitation has the highest recommendation in current guidelines. While treatment target attainment rates at Swedish cardiac rehabilitation centres is among the highest in Europe, there are considerable differences in service delivery and variations in patient-level outcomes between centres. In this trial, we aim to study whether centre-level guideline adherence and patient-level outcomes across Swedish cardiac rehabilitation centres can be improved through a) regular audit and feedback of cardiac rehabilitation structure and processes through a national quality registry and b) supporting cardiac rehabilitation centres in implementing guidelines on secondary prevention. Furthermore, we aim to evaluate the implementation process and costs.

    Methods

    The study is an open-label cluster-randomized effectiveness-implementation hybrid trial including all 78 cardiac rehabilitation centres (attending to approximately 10 000 MI patients/year) that report to the SWEDEHEART registry. The centres will be randomized 1:1:1 to three clusters: 1) reporting cardiac rehabilitation structure and process variables to SWEDEHEART every six months (audit intervention) and being offered implementation support to implement guidelines on secondary prevention (implementation support intervention); 2) audit intervention only; or 3) no intervention offered. Baseline cardiac rehabilitation structure and process variables will be collected. The primary outcome is an adherence score measuring centre-level adherence to secondary prevention guidelines. Secondary outcomes include patient-level secondary prevention risk factor goal attainment at one-year after MI and major adverse coronary outcomes for up to five-years post-MI. Implementation outcomes include barriers and facilitators to guideline adherence evaluated using semi-structured focus-group interviews and relevant questionnaires, as well as costs and cost-effectiveness assessed by a comparative health economic evaluation.

    Discussion

    Optimizing cardiac rehabilitation centres’ delivery of services to meet standards set in guidelines may lead to improvement in cardiovascular risk factors, including lifestyle factors, and ultimately a decrease in morbidity and mortality after MI.

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  • 17939. Öhman, Lena
    et al.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Isaksson, Stefan
    Jerlstad, Pernilla
    Simrén, Magnus
    Altered Levels of Fecal Chromogranins and Secretogranins in IBS: Relevance for Pathophysiology and Symptoms?2012In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 107, no 3, p. 440-447Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    Chromogranins (Cg) and secretogranins (Sg) are proteins ubiquitous in secretory cells of the enteric, endocrine, and immune systems, and may reflect activity of these systems. We therefore performed a hypothesis generating study to evaluate the association between fecal levels of CgA, CgB, SgII, and SgIII, with the clinical and pathophysiological phenotype of irritable bowel syndrome (IBS) patients.

    METHODS:

    Analyses of CgA, CgB, SgII, SgIII, and calprotectin in fecal samples of 82 IBS patients and 29 healthy controls were performed. All IBS subjects completed validated questionnaires to assess gastrointestinal and psychological symptom severity, and underwent rectal barostat test and colonic transit time measurement.

    RESULTS:

    IBS patients demonstrated higher levels of fecal CgA (P=0.009), SgII (P<0.001), and SgIII (P<0.001), but lower levels of CgB (P<0.001) compared with controls. SgII had good discriminative validity to positively identify IBS patients, with an area under the receiver operating characteristics (ROC) curve (AUROC) of 0.86 (95% confidence interval (CI): 0.78-0.94). SgIII and CgB both had fairly good discriminative validity to positively identify IBS patients, with an AUROC of 0.79 (95% CI: 0.71-0.87) and 0.78 (95% CI: 0.69-0.87), respectively. There were negative correlations between the colonic transit time and fecal levels of CgA (r=-0.53, P<0.001), SgII (r=-0.55, P<0.001), and SgIII (r=-0.28, P=0.03). Perceived abdominal pain was moderately associated with levels of CgA (r=0.32, P=0.004), SgII (r=0.31, P=0.006), and SgIII (r=0.24, P=0.04). Calprotectin levels were not associated with the levels of granins or with the clinical or pathophysiological phenotype of IBS patients.

    CONCLUSIONS:

    Fecal levels of Cg and Sg may be related to the underlying pathophysiology of IBS and of potential importance for symptoms of the patients. Granins also show promise to serve as future biomarkers of IBS. Further studies are needed to explore the potential role of granins in IBS patients.

  • 17940.
    Öhman, Marie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Åkerfeldt, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Nilsson, Ingela
    Rosen, Christer
    Hansson, Lars-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Biochemical effects of consumption of eggs containing omega-3 polyunsaturated fatty acids2008In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 113, no 3, p. 315-323Article in journal (Refereed)
    Abstract [en]

    Today, eggs with an increased content of -3 fatty acids are available but there are few publications on the effects of consumption of such eggs on the lipoproteins and acute phase markers in humans. The aim of the present study was to evaluate the effects of consumption of standard eggs and -3 enriched eggs on lipoproteins, glucose and inflammation markers. Nineteen healthy volunteers consumed one extra egg per day of either standard eggs or omega-3 enriched eggs in a double-blind, cross-over study. The duration of each period was 1 month. The effects of the different egg diets on apolipoprotein A1 and B (Apo A1 and B), lipoprotein (a), creatinine, cystatin C, C-reactive protein, serum amyloid protein A, interleukin 6, triglycerides, glucose, total-, high-density lipoprotein and low-density lipo-protein cholesterol concentrations were analyzed. Addition of one regular egg per day to the normal diet had no negative impact on blood lipids or inflammation markers. Consumption of omega-3 enriched eggs resulted in higher levels of ApoA1, lower ApoB/ApoA1 ratio and lower plasma glucose. These effects have been associated in previous studies with a reduced risk for cardiovascular mortality and diabetes.

  • 17941.
    Öhrmalm, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Eriksson, Ronnie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Jobs, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Simonson, Magnus
    Naitonal Food Agency, Uppsala.
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Bondeson, Kåre
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Herrmann, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Blomberg, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Variation-tolerant capture and multiplex detection of nucleic acids: application to detection of microbes2012In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 50, no 10, p. 3208-3215Article in journal (Refereed)
    Abstract [en]

    In contrast to ordinary PCRs, which have a limited multiplex capacity and often return false-negative results due to target variation or inhibition, our new detection strategy, VOCMA (variation-tolerant capture multiplex assay), allows variation-tolerant, target-specific capture and detection of many nucleic acids in one test. Here we demonstrate the use of a single-tube, dual-step amplification strategy that overcomes the usual limitations of PCR multiplexing, allowing at least a 22-plex format with retained sensitivity. Variation tolerance was achieved using long primers and probes designed to withstand variation at known sites and a judicious mix of degeneration and universal bases. We tested VOCMA in situations where enrichment from a large sample volume with high sensitivity and multiplexity is important (sepsis; streptococci, enterococci, and staphylococci, several enterobacteria, candida, and the most important antibiotic resistance genes) and where variation tolerance and high multiplexity is important (gastroenteritis; astrovirus, adenovirus, rotavirus, norovirus genogroups I and II, and sapovirus, as well as enteroviruses, which are not associated with gastroenteritis). Detection sensitivities of 10 to 1,000 copies per reaction were achieved for many targets. VOCMA is a highly multiplex, variation-tolerant, general purpose nucleic acid detection concept. It is a specific and sensitive method for simultaneous detection of nucleic acids from viruses, bacteria, fungi, and protozoa, as well as host nucleic acid, in the same test. It can be run on an ordinary PCR and a Luminex machine and is suitable for both clinical diagnoses and microbial surveillance.

  • 17942.
    Öhrmalm, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jobs, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Eriksson, Ronnie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Golbob, Sultan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Elfaitouri, Amal
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Benachenhou, Farid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Blomberg, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Hybridization properties of long nucleic acid probes for detection of variable target sequences, and development of a hybridization prediction algorithm2010In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 38, no 21, p. e195-Article in journal (Refereed)
    Abstract [en]

    One of the main problems in nucleic acid-based techniques for detection of infectious agents, such as influenza viruses, is that of nucleic acid sequence variation. DNA probes, 70-nt long, some including the nucleotide analog deoxyribose-Inosine (dInosine), were analyzed for hybridization tolerance to different amounts and distributions of mismatching bases, e.g. synonymous mutations, in target DNA. Microsphere-linked 70-mer probes were hybridized in 3M TMAC buffer to biotinylated single-stranded (ss) DNA for subsequent analysis in a Luminex® system. When mismatches interrupted contiguous matching stretches of 6 nt or longer, it had a strong impact on hybridization. Contiguous matching stretches are more important than the same number of matching nucleotides separated by mismatches into several regions. dInosine, but not 5-nitroindole, substitutions at mismatching positions stabilized hybridization remarkably well, comparable to N (4-fold) wobbles in the same positions. In contrast to shorter probes, 70-nt probes with judiciously placed dInosine substitutions and/or wobble positions were remarkably mismatch tolerant, with preserved specificity. An algorithm, NucZip, was constructed to model the nucleation and zipping phases of hybridization, integrating both local and distant binding contributions. It predicted hybridization more exactly than previous algorithms, and has the potential to guide the design of variation-tolerant yet specific probes.

  • 17943.
    Öhrmalm, L.
    et al.
    Karolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med,Infect Dis Unit, Solna, Sweden..
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Wong, M.
    Karolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med,Infect Dis Unit, Solna, Sweden..
    Levinson, P.
    Karolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med,Infect Dis Unit, Solna, Sweden..
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Broliden, K.
    Karolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med,Infect Dis Unit, Solna, Sweden..
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Presence of rhinovirus in the respiratory tract of adolescents and young adults with asthma without symptoms of infection2016In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 115, p. 1-6Article in journal (Refereed)
    Abstract [en]

    Background: Viral respiratory infections have been associated with up to 80% of wheezing episodes and asthma exacerbations. However, studies on the role of these viruses in asthmatic patients in the interval between exacerbations are sparse. This study aimed to determine the presence of respiratory viruses, without symptoms of infection, in the airways of young asthmatics as compared to healthy controls.

    Material and Methods: Patients 10-35 years of age with stable asthma and a group of healthy controls were analyzed regarding the presence of RNA from common respiratory viruses in nasopharyngeal aspirates by PCR. Self-reported asthma control and quality of life, fraction of exhaled nitric oxide (FeNO), spirometry, and bronchial responsiveness to methacholine were recorded. Blood samples were collected to assess IgE sensitisation and eosinophil cationic protein (ECP) levels.

    Results: In 354 patients with asthma and 108 healthy controls, human rhinovirus (HRV) was the only virus detected (4.5% of asthmatics vs. 0.9% of controls; p = 0.08). HRV+ asthma patients had a higher degree of aeroallergen IgE sensitisation (median 37.7 vs. 10.4 kU(A)/L, p = 0.04), and a tendency for higher levels of serum ECP (median 17.2 vs. 12.6 mu g/L, p = 0.07), as compared to their HRV- counterparts.

    Conclusions: Absence of symptoms of respiratory tract infection notwithstanding, HRV seems to be more prevalent in the airways of adolescents and young adults with asthma and a high degree of aeroallergen IgE sensitisation than in controls. The presence of HRV seems also to be related to systemic eosinophilic inflammation despite ongoing treatment with inhaled corticosteroids.

  • 17944. Öhrvall, Ulf
    et al.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Juhlin, Claes
    Karacagil, Sadettin
    Rastad, Jonas
    Hellman, Per
    Åkerström, Göran
    Method for dissection of mesenteric metastases in mid-gut carcinoid tumors2000In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 24, no 11, p. 1402-1408Article in journal (Refereed)
    Abstract [en]

    With adequate medical management the midgut carcinoid tumor generally is an indolent malignancy associated with substantial life expectancy and appreciable life quality, even in the presence of liver metastases and significant tumor burden. Abdominal complications may occur in this entity of carcinoids owing to entrapment of intestines and encasement of mesenteric vessels by mesenteric metastases and associated marked mesenteric fibrosis. This may be the cause of abdominal pain, disabling diarrhea, weight loss to the extent of malnutrition, and eventually the risk of death with acute or chronic intestinal obstruction or intestinal gangrene. Operative removal of the mesentericointestinal lesion is often indicated to prevent or treat these complications but may be technically difficult when mesenteric metastases extend in the vicinity of major vessels in the mesenteric root. At laparotomy 56 patients with advanced midgut carcinoids underwent removal of the mesenteric tumor with a method for preserving the mesenteric vessels. This was feasible by mobilizing and releasing the right colon and mesenteric root from posterior adhesions, identifying the mesenteric artery below the pancreas, and free-dissecting this artery on the tumor capsule in the mobilized mesentery. Dissection was successful even with tumors initially judged inoperable unless tumor growth completely surrounded the mesenteric vessels or extended retroperitoneally. One patient was subjected to distal intestinal artery bypass. Symptom relief was been substantial and often of long duration after mesenteric tumor removal in patients who prior to surgery often had threatening intestinal ischemia. Patients with advanced midgut carcinoids may benefit markedly from dissectional removal of mesenteric tumors, which (conceivably better than conventional wedge resection) preserves the length of the remaining intestine.

  • 17945. Öhrvik, Veronica
    et al.
    Warensjö, Eva
    Science DepartmentNational Food AgencyUppsalaSweden.
    Nälsén, Cecilia
    Becker, Wulf
    Ridefelt, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lindroos, Anna Karin
    Dietary intake and biomarker status of folate in Swedish adults2018In: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 57, no 2, p. 451-462Article in journal (Refereed)
    Abstract [en]

    PURPOSE: National data on folate status are missing in Sweden, and regional data indicate folate insufficiency in up to more than 25% of the study populations. The objectives were to determine folate intake and status in the adult Swedish population as well as identifying dietary patterns associated with beneficial folate status.

    METHODS: Folate intake was estimated using a web-based 4-d food record in adults aged 18-80 years (n = 1797). Folate status was measured as erythrocyte (n = 282) and plasma folate concentrations (n = 294). Factor analysis was used to derive a dietary pattern associated with a higher folate status.

    RESULTS: Median folate intake was 246 µg/day (Q 1 = 196, Q 3 = 304, n = 1797) and for women of reproductive age 227 µg/day (Q 1 = 181, Q 3 = 282, n = 450). As dietary folate equivalents (DFE), median intake was 257 µg/day (Q 1 = 201, Q 3 = 323) and for women of reproductive age 239 µg/day (Q 1 = 185, Q 3 = 300). Low blood folate concentrations were found in 2% (erythrocyte concentrations <317 nmol/L) and 4% (plasma concentrations <6.8 nmol/L) of the participants, respectively. None of the women of reproductive age had erythrocyte folate concentrations associated with the lowest risk of neural tube defects. Dietary patterns associated with higher folate status were rich in vegetables, pulses and roots as well as cheese and alcoholic beverages, and low in meat.

    CONCLUSIONS: Prevalence of low erythrocyte folate concentrations was low in this population, and estimated dietary intakes are well above average requirement. However, to obtain a folate status optimal for prevention of neural tube defects major dietary changes are required and folic acid supplements recommended prior to conception.

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  • 17946.
    Ölander, Christine
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Buddee Roos, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Eriksson, Per Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Johansson, Hemming
    Institutionen för onkologi-patologi, Karolinska institutet.
    Danckwardt-Lillieström, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Gudjonsson, Olafur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    A Decade Later: Assessing Hearing Preservation in Vestibular Schwannoma Patients Post Middle Cranial Fossa Surgery: Long-term hearing outcomes of MCF surgeryManuscript (preprint) (Other academic)
  • 17947. Önskog, Jenny
    et al.
    Freyhult, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Landfors, Mattias
    Ryden, Patrik
    Hvidsten, Torgeir R.
    Classification of microarrays: synergistic effects between normalization, gene selection and machine learning2011In: BMC Bioinformatics, E-ISSN 1471-2105, Vol. 12, p. 390-Article in journal (Refereed)
    Abstract [en]

    Background: Machine learning is a powerful approach for describing and predicting classes in microarray data. Although several comparative studies have investigated the relative performance of various machine learning methods, these often do not account for the fact that performance (e. g. error rate) is a result of a series of analysis steps of which the most important are data normalization, gene selection and machine learning. Results: In this study, we used seven previously published cancer-related microarray data sets to compare the effects on classification performance of five normalization methods, three gene selection methods with 21 different numbers of selected genes and eight machine learning methods. Performance in term of error rate was rigorously estimated by repeatedly employing a double cross validation approach. Since performance varies greatly between data sets, we devised an analysis method that first compares methods within individual data sets and then visualizes the comparisons across data sets. We discovered both well performing individual methods and synergies between different methods. Conclusion: Support Vector Machines with a radial basis kernel, linear kernel or polynomial kernel of degree 2 all performed consistently well across data sets. We show that there is a synergistic relationship between these methods and gene selection based on the T-test and the selection of a relatively high number of genes. Also, we find that these methods benefit significantly from using normalized data, although it is hard to draw general conclusions about the relative performance of different normalization procedures.

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  • 17948.
    Örlefors, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Positron Emission Tomography in the Management of Neuroendocrine Tumors2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Neuroendocrine tumors (NET´s) are often characterized by overproduction of peptide hormones. In spite of pronounced clinical symptoms, the tumor lesions can be small and difficult to detect. The general aim of this thesis was to investigate, in vitro and in vivo, some of the potential monoamine pathways present in NET´s, using radiolabeled tracers for positron emission tomography (PET), with the intention to explore the value of PET-imaging in the management of NET´s.

    We used the 11C-labeled serotonin precursor 5-hydroxy tryptophan (HTP) as the tracer for imaging of NET´s. More than 95% of the subjects displayed a high tracer uptake on PET and tumor detection rate with PET was higher in >50% of the patients compared both to computed tomography (CT) and somatostatin receptor scintigraphy (SRS). The primary tumor was imaged by PET in 84% (16/19), compared to 47% and 42% for SRS and CT, respectively. Tumor visibility was better with PET due to a higher tumor-to-background ratio and a better spatial resolution. There was a strong correlation (r = .907) between changes in urinary-5-hydroxy indole acetic acid and changes in transport rate of 11C-5-HTP during treatment, indicating the use of PET in treatment monitoring of NET´s.

    Pretreatment with carbidopa decreased the urinary radioactivity concentration four-fold and significantly (p<0.001) increased the tumor tracer uptake. This greatly improved image interpretation and tumor lesion detection.

    A screening for expression of monoamine pathways in NET´s revealed a high in vitro binding of the monoamineoxidase-A ligand harmine to tumor sections. PET examinations with 11C-harmine could visualize tumors in all patients, including non-functioning endocrine pancreatic tumors (EPT´s).

    Finally, the in vitro turnover and in vivo distribution of the amino acids glutamate, glutamine and aspartate was investigated. Limited uptake in vivo indicates the lack of utility for these substances as PET-tracers for imaging and characterization of NET´s.

    List of papers
    1. Positron Emission Tomography with 5-hydroxytryptophan
    Open this publication in new window or tab >>Positron Emission Tomography with 5-hydroxytryptophan
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    1998 (English)In: Journal of Clinical Oncology, Vol. 16, no 7, p. 2534-2542Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-90208 (URN)
    Available from: 2003-04-24 Created: 2003-04-24 Last updated: 2011-03-23Bibliographically approved
    2. Uptake of 14C- and 11C-labeled glutamate, glutamine and aspartate in vitro and in vivo
    Open this publication in new window or tab >>Uptake of 14C- and 11C-labeled glutamate, glutamine and aspartate in vitro and in vivo
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    2000 In: Anticancer Research, no 20, p. 251-256Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-90209 (URN)
    Available from: 2003-04-24 Created: 2003-04-24 Last updated: 2015-09-24Bibliographically approved
    3. Demonstration of high monoamineoxidase-A levels in neuroendocrine gastroenteropancreatic tumors in vitro and in vivo: tumor visualization using positron emission tomography with 11C-harmine
    Open this publication in new window or tab >>Demonstration of high monoamineoxidase-A levels in neuroendocrine gastroenteropancreatic tumors in vitro and in vivo: tumor visualization using positron emission tomography with 11C-harmine
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    2003 (English)In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 30, no 6, p. 669-679Article in journal (Refereed) Published
    Abstract [en]

    Background and Aims: A majority of neuroendocrine gastroenteropancreatic (GEP) tumors can be detected by conventional radiological methods and scintigraphic techniques. Still there are problems to visualize small tumor lesions and non-functioning tumors. The aim of this study was to investigate some of the monoamine processing pathways of neuroendocrine GEP-tumors and try to find a new tracer substance for in vivo characterization and visualization by Positron Emission Tomography (PET).

    Subjects and Methods: Autoradiography of tumor sections from 8 midgut carcinoids (MGC) and 8 endocrine pancreatic tumors (EPT) was performed with C-11-labeled tracers for serotonin and dopamine transporters, serotonin HT2A-, dopamine D1- and muscarinic receptors and for monoamine oxidase A (MAO-A). The in vitro results initiated PET studies with C-11-Harmine in 4 patients with MGC and 7 patients with EPT (one insulinoma, two glucagonomas and four non-functioning EPT).

    Results: The MAO-A-ligand Harmine expressed specific in vitro binding of 87 +/- 21% for MGC and 125 +/- 50% for EPT, compared to reference tissue (rat brain, 100%). All other substances showed relatively low specific binding. C-11-harmine-PET could visualize tumors in all patients. The mean standardized uptake value (SUV) for MGC was 7.5 +/- 3.9 and for EPT 12.9 +/- 2.7, whereas the SUV of normal liver, intestine and pancreas were 3.1 +/- 0.5, 3.4 +/- 1.2 and 8.9 +/- 3.0 respectively. Conclusions: This study demonstrates in vitro and in vivo that neuroendocrine GEP-tumors are characterized by a high MAO-A-expression, thereby adding to the similarities of neuronal and neuroendocrine tissue. It also indicates a possible application for C-11-harmine as a new PET-tracer for neuroendocrine GEP-tumors with the potential to visualize also non-functioning EPT's.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-90210 (URN)10.1016/S0969-8051(03)00034-9 (DOI)
    Available from: 2003-04-24 Created: 2003-04-24 Last updated: 2017-12-14Bibliographically approved
    4. Whole-body 11C-5-HTP-PET as a general imaging technique for detection of Neuroendocrine tumors - a comparison with somatostatin receptor scintigraphy and computed tomography
    Open this publication in new window or tab >>Whole-body 11C-5-HTP-PET as a general imaging technique for detection of Neuroendocrine tumors - a comparison with somatostatin receptor scintigraphy and computed tomography
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    Manuscript (Other academic)
    Identifiers
    urn:nbn:se:uu:diva-90211 (URN)
    Available from: 2003-04-24 Created: 2003-04-24 Last updated: 2010-01-13Bibliographically approved
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  • 17949.
    Örlefors, Håkan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundin, Anders
    Ahlström, Håkan
    Bjurling, Peter
    Bergström, Mats
    Lilja, Anders
    Långström, Bengt
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Positron Emission Tomography with 5-hydroxytryptophan1998In: Journal of Clinical Oncology, Vol. 16, no 7, p. 2534-2542Article in journal (Refereed)
  • 17950.
    Örlefors, Håkan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    PET-Guided Surgery: High Correlation between Positron Emission Tomography with 11C-5-Hydroxytryptophane (5-HTP) and Surgical Findings in Abdominal Neuroendocrine Tumours2012In: Cancers, ISSN 2072-6694, Vol. 4, no 1, p. 100-112Article in journal (Other academic)
    Abstract [en]

    Positron emission tomography (PET) with 11C-labeled 5-hydroxytryptophane (5-HTP) is a sensitive technique to visualize neuroendocrine tumours (NETs), due to high intracellular uptake of amine-precursors like L-dihydroxyphenylalanine (L-DOPA) and 5-HTP. NETs are often small and difficult to localize in spite of overt clinical symptoms due to hormonal excess. In our study, 38 consecutive NET patients underwent 11C-5-HTP-PET and morphological imaging by CT within 12 weeks prior to surgery. Surgical, histopathological and 5-HTP PET findings were correlated. 11C-5-HTP-PET corresponded to the surgical findings in 31 cases, was false negative in six, and true negative in one case resulting in 83.8% sensitivity and 100% specificity. Positive predicted value was 100%. In 11 patients 11C-5-HTP-PET was the only imaging method applied to localize the tumour. Thus, we could demonstrate that functional imaging by 11C-5-HTP-PET in many cases adds vital preoperative diagnostic information and in more than every fourth patient was the only imaging method that will guide the surgeon in finding the NET-lesion. Although the present results demonstrates that 11C-5-HTP may be used as an universal NET tracer, the sensitivity to visualize benign insulinomas and non functioning pancreatic NETs was lower.

356357358359360 17901 - 17950 of 17988
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