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Krifors, A., Blennow, O., Påhlman, L. I., Gille-Johnson, P., Janols, H., Lipcsey, M., . . . Castegren, M. (2024). Influenza-associated invasive aspergillosis in patients admitted to the intensive care unit in Sweden: a prospective multicentre cohort study. Infectious Diseases, 56(2), 110-115
Open this publication in new window or tab >>Influenza-associated invasive aspergillosis in patients admitted to the intensive care unit in Sweden: a prospective multicentre cohort study
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2024 (English)In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 56, no 2, p. 110-115Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The purpose of this study was to prospectively investigate the incidence of influenza-associated pulmonary aspergillosis (IAPA) in influenza patients admitted to intensive care units in Sweden.

METHODS: The study included consecutive adult patients with PCR-verified influenza A or B in 12 Swedish intensive care units (ICUs) over four influenza seasons (2019-2023). Patients were screened using serum galactomannan and β-d-glucan tests and fungal culture of a respiratory sample at inclusion and weekly during the ICU stay. Bronchoalveolar lavage was performed if clinically feasible. IAPA was classified according to recently proposed case definitions.

RESULTS: The cohort included 55 patients; 42% were female, and the median age was 59 (IQR 48-71) years. All patients had at least one galactomannan test, β-d-glucan test and respiratory culture performed. Bronchoalveolar lavage was performed in 24 (44%) of the patients. Five (9%, 95% CI 3.8% - 20.4%) patients were classified as probable IAPA, of which four lacked classical risk factors. The overall ICU mortality was significantly higher among IAPA patients than non-IAPA patients (60% vs 8%, p = 0.01).

CONCLUSIONS: The study represents the first prospective investigation of IAPA incidence. The 9% incidence of IAPA confirms the increased risk of invasive pulmonary aspergillosis among influenza patients admitted to the ICU. Therefore, it appears reasonable to implement a screening protocol for the early diagnosis and treatment of IAPA in influenza patients receiving intensive care.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04172610, registered November 21, 2019.

Place, publisher, year, edition, pages
Taylor & Francis, 2024
Keywords
Influenza, influenza-associated aspergillosis, intensive care medicine, invasive aspergillosis
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-517175 (URN)10.1080/23744235.2023.2273381 (DOI)001089231700001 ()37897800 (PubMedID)
Available from: 2023-12-04 Created: 2023-12-04 Last updated: 2024-03-01Bibliographically approved
Eklund, R., Hjelmfors, L., Nyquist, S., Sveen, J., Hultström, M., Lipcsey, M., . . . Orwelius, L. (2024). Surviving COVID-19: patients' experiences of care and path to recovery. International Journal of Qualitative Studies on Health and Well-being, 19(1), Article ID 2301953.
Open this publication in new window or tab >>Surviving COVID-19: patients' experiences of care and path to recovery
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2024 (English)In: International Journal of Qualitative Studies on Health and Well-being, ISSN 1748-2623, E-ISSN 1748-2631, Vol. 19, no 1, article id 2301953Article in journal (Refereed) Published
Abstract [en]

Purpose: To examine patients' experiences of receiving care on an ICU for COVID-19 and the subsequent rehabilitation process.

Methods: An explorative and inductive design was used. Participants were recruited from two university hospitals in Sweden. Patients admitted to the ICU due to COVID-19 from March 2020 to April 2021, who enrolled in the ICU follow-up, and understood and spoke Swedish were invited to participate. In total, 20 participants completed a semi-structured interview, of whom 18 were included in the thematic analysis.

Results: The analysis resulted in two themes: "An isolated world with silver linings" and "Recovery in the wake of the pandemic". Findings show that patients cared for on an ICU for COVID-19 during the pandemic felt safe but experienced a sense of vulnerability. After discharge, physical rehabilitation was a slow process with frustrating day-to-day fluctuations. Mentally, participants felt isolated, fatigued, and emotionally sensitive. Patients reported that love and support from family and friends were crucial for the recovery process.

Conclusions: This study highlights the challenges of recovering from COVID-19, emphasizing the importance of continued support from health care, public services, family and friends. It provides important insights into patients' experiences and can inform future healthcare strategies and policies.

Place, publisher, year, edition, pages
Taylor & Francis, 2024
Keywords
COVID-19, intensive care, psychosocial well-being, psychosocial support, recovery, rehabilitation
National Category
Nursing
Identifiers
urn:nbn:se:uu:diva-521174 (URN)10.1080/17482631.2024.2301953 (DOI)001137343700001 ()38184794 (PubMedID)
Funder
Region Östergötland, ROE-978823
Available from: 2024-01-24 Created: 2024-01-24 Last updated: 2024-01-24Bibliographically approved
(2023). A second update on mapping the human genetic architecture of COVID-19 [Letter to the editor]. Nature, 621(7977), E7-E26
Open this publication in new window or tab >>A second update on mapping the human genetic architecture of COVID-19
2023 (English)In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 621, no 7977, p. E7-E26Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
Springer Nature, 2023
National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-523980 (URN)10.1038/s41586-023-06355-3 (DOI)001112777800001 ()37674002 (PubMedID)
Note

Robert Frithiof, Michael Hultström and Miklos Lipcsey are data collection members in The COVID-19 Host Genetics Initiative

For complete list of contributors see http://dx.doi.org/10.1038/s41586-023-06355-3

Available from: 2024-02-27 Created: 2024-02-27 Last updated: 2024-02-27Bibliographically approved
Bergström, A., Lipcsey, M., Larsson, A., Yang, B., Engblom, D., Chew, M. S. & Elander, L. (2023). Acetaminophen Attenuates Pulmonary Vascular Resistance and Pulmonary Arterial Pressure and Inhibits Cardiovascular Collapse in a Porcine Model of Endotoxemia. Shock, 59(3), 442-448
Open this publication in new window or tab >>Acetaminophen Attenuates Pulmonary Vascular Resistance and Pulmonary Arterial Pressure and Inhibits Cardiovascular Collapse in a Porcine Model of Endotoxemia
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2023 (English)In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 59, no 3, p. 442-448Article in journal (Refereed) Published
Abstract [en]

Acetaminophen (paracetamol) is often used in critically ill patients with fever and pain; however, little is known about the effects of acetaminophen on cardiovascular function during systemic inflammation. Here, we investigated the effect of acetaminophen on changes in the systemic and pulmonary circulation induced by endotoxin (0.5 μg/kg/h) in anesthetized pigs. Endotoxin infusion led to a rapid increase in pulmonary artery (PA)-pressure and pulmonary vascular resistance index (PVRI). Acetaminophen delayed and attenuated this increase. Furthermore, acetaminophen reduced tachycardia and decreased stroke volume, accompanied by systemic inflammation, without affecting inflammatory parameters such as white blood cell count and TNF-α in blood. As a proof of concept, we injected a high dose of endotoxin (100 μg), which induced rapid cardiovascular collapse in pigs. Pigs treated with acetaminophen survived with no obvious hemodynamic instability during the 50 min observation period. In conclusion, acetaminophen attenuates the effects of endotoxin on pulmonary circulation in anesthetized pigs. This may play a role in severe systemic inflammation.

Place, publisher, year, edition, pages
Shock Society, 2023
Keywords
Acetaminophen, cardiovascular, endotoxin, inflammation, MPAP
National Category
Anesthesiology and Intensive Care Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-492578 (URN)10.1097/SHK.0000000000002061 (DOI)000943272500016 ()36597769 (PubMedID)
Funder
Region Östergötland, RÖ-690421Region Sörmland, DLL-977570
Available from: 2023-01-06 Created: 2023-01-06 Last updated: 2023-04-13Bibliographically approved
Krifors, A., Lignell, A., Lipcsey, M., Sjölin, J. & Castegren, M. (2023). An experimental porcine model of invasive candidiasis. Intensive Care Medicine Experimental, 11(1), Article ID 27.
Open this publication in new window or tab >>An experimental porcine model of invasive candidiasis
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2023 (English)In: Intensive Care Medicine Experimental, E-ISSN 2197-425X, Vol. 11, no 1, article id 27Article in journal (Refereed) Published
Abstract [en]

Background

Invasive candidiasis (IC) is a severe and often fatal fungal infection that affects critically ill patients. The development of animal models that mimic human disease is essential for advancing our understanding of IC pathophysiology and testing experimental or novel treatments. We aimed to develop a large animal model of IC that could provide a much-needed addition to the widely used murine models.

Results

A total of 25 pigs (including one control), aged between 9 and 12 weeks, with a median weight of 25.1 kg (IQR 24.1–26.2), were used to develop the porcine IC model. We present the setup, the results of the experiments, and the justification for the changes made to the model. The experiments were conducted in an intensive care setting, using clinically relevant anaesthesia, monitoring and interventions. The final model used corticosteroids, repeated Candida inoculation, and continuous endotoxin. The model consistently demonstrated quantifiable growth of Candida in blood and organs. The registered physiological data supported the development of the sepsis-induced circulatory distress observed in IC patients in the ICU.

Conclusions

Our proposed porcine model of IC offers a potential new tool in the research of IC.

Place, publisher, year, edition, pages
Springer NatureSpringer Nature, 2023
National Category
Anesthesiology and Intensive Care Microbiology in the medical area
Identifiers
urn:nbn:se:uu:diva-503101 (URN)10.1186/s40635-023-00514-6 (DOI)000986487200001 ()37183195 (PubMedID)
Funder
Karolinska Institute
Available from: 2023-06-08 Created: 2023-06-08 Last updated: 2024-01-15Bibliographically approved
Havelka, A., Larsson, A. O., Mårtensson, J., Bell, M., Hultström, M., Lipcsey, M. & Eriksson, M. (2023). Analysis of Calprotectin as an Early Marker of Infections Is Economically Advantageous in Intensive Care-Treated Patients. Biomedicines, 11(8), Article ID 2156.
Open this publication in new window or tab >>Analysis of Calprotectin as an Early Marker of Infections Is Economically Advantageous in Intensive Care-Treated Patients
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2023 (English)In: Biomedicines, E-ISSN 2227-9059, Vol. 11, no 8, article id 2156Article in journal (Refereed) Published
Abstract [en]

Calprotectin is released from neutrophil granulocytes upon activation. Several studies have indicated that plasma calprotectin is an early determinant of bacterial infections, which may serve as a diagnostic tool facilitating decision making on antibiotic treatment. The study objective was to explore the health and economic implications of calprotectin as a predictive tool to initiate antimicrobial therapy in a cohort of critically ill patients. Thus, data obtained from a previously published study on calprotectin as a hypothetical early biomarker of bacterial infections in critically ill patients were evaluated regarding the potential cost-effective impact of early analysis of calprotectin on an earlier start of antibiotic treatment. Under the assumption that calprotectin is used predictively and comparators (white blood cells, procalcitonin, and C-reactive protein) are used diagnostically, a cost-effective impact of EUR 11,000-12,000 per patient would be obtained. If calprotectin would be used predictively and comparators would be used predictively for 50% of patients, it is hypothesized that cost-effectiveness would be between EUR 6000 and 7000 per patient, based on reduced stay in the ICU and general ward, respectively. Furthermore, predictive use of calprotectin seems to reduce both mortality and the length of hospital stay. This health economic analysis on the predictive use of plasma calprotectin, which facilitates clinical decision making in cases of suspected sepsis, indicates that such determination has a cost-saving and life-saving impact on the healthcare system.

Place, publisher, year, edition, pages
MDPI, 2023
Keywords
calprotectin, costs, early detection, economic modeling, infection, intensive care, sepsis
National Category
Anesthesiology and Intensive Care Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-510296 (URN)10.3390/biomedicines11082156 (DOI)001055404400001 ()37626653 (PubMedID)
Available from: 2023-08-27 Created: 2023-08-27 Last updated: 2023-09-26Bibliographically approved
Karlsson, P. A., Pärssinen, J., Danielsson, E. A., Fatsis-Kavalopoulos, N., Frithiof, R., Hultström, M., . . . Wang, H. (2023). Antibiotic use during coronavirus disease 2019 intensive care unit shape multidrug resistance bacteriuria: A Swedish longitudinal prospective study. Frontiers in Medicine, 10, Article ID 1087446.
Open this publication in new window or tab >>Antibiotic use during coronavirus disease 2019 intensive care unit shape multidrug resistance bacteriuria: A Swedish longitudinal prospective study
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2023 (English)In: Frontiers in Medicine, E-ISSN 2296-858X, Vol. 10, article id 1087446Article in journal (Refereed) Published
Abstract [en]

Objectives: High frequency of antimicrobial prescription and the nature of prolonged illness in COVID-19 increases risk for complicated bacteriuria and antibiotic resistance. We investigated risk factors for bacteriuria in the ICU and the correlation between antibiotic treatment and persistent bacteria.

Methods: We conducted a prospective longitudinal study with urine from indwelling catheters of 101 ICU patients from Uppsala University Hospital, Sweden. Samples were screened and isolates confirmed with MALDI-TOF and whole genome sequencing. Isolates were analyzed for AMR using broth microdilution. Clinical data were assessed for correlation with bacteriuria.

Results: Length of stay linearly correlated with bacteriuria (R2 = 0.99, p ≤ 0.0001). 90% of patients received antibiotics, primarily the beta-lactams (76%) cefotaxime, piperacillin-tazobactam, and meropenem. We found high prevalence of Enterococcus (42%) being associated with increased cefotaxime prescription. Antibiotic-susceptible E. coli were found to cause bacteriuria despite concurrent antibiotic treatment when found in co-culture with Enterococcus.

Conclusion: Longer stays in ICUs increase the risk for bacteriuria in a predictable manner. Likely, high use of cefotaxime drives Enterococcus prevalence, which in turn permit co-colonizing Gram-negative bacteria. Our results suggest biofilms in urinary catheters as a reservoir of pathogenic bacteria with the potential to develop and disseminate AMR.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2023
Keywords
UTI, ICU–intensive care unit, COVID-19, MDR–(multidrug resistance), AMR, antibiotic treatment, catheters
National Category
Anesthesiology and Intensive Care Infectious Medicine Urology and Nephrology Microbiology in the medical area Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Anaesthesiology and Intensive Care; Microbiology; Epidemiology; Urology; Pharmaceutical Microbiology; Clinical Bacteriology; Clinical Pharmacology
Identifiers
urn:nbn:se:uu:diva-496102 (URN)10.3389/fmed.2023.1087446 (DOI)000934136200001 ()36824610 (PubMedID)
Funder
Swedish Society for Medical Research (SSMF), S18-0174Swedish Research Council, 2018-02376Swedish Research Council, 2014-02569Swedish Research Council, 2014-07606Knut and Alice Wallenberg Foundation, 2020.0182Knut and Alice Wallenberg Foundation, 2020.0241Swedish Heart Lung Foundation, 20210089Swedish Heart Lung Foundation, 20190639Swedish Heart Lung Foundation, 20190637The Swedish Kidney Foundation, F2020-0054Science for Life Laboratory, SciLifeLab
Available from: 2023-02-07 Created: 2023-02-07 Last updated: 2023-10-18Bibliographically approved
Strandberg, G. & Lipcsey, M. (2023). Association of socioeconomic and demographic factors with limitations of life sustaining treatment in the intensive care unit [Letter to the editor]. Intensive Care Medicine, 49(10), 1249-1250
Open this publication in new window or tab >>Association of socioeconomic and demographic factors with limitations of life sustaining treatment in the intensive care unit
2023 (English)In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 49, no 10, p. 1249-1250Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Springer Nature, 2023
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-514524 (URN)10.1007/s00134-023-07177-7 (DOI)001048714800001 ()37580572 (PubMedID)
Available from: 2023-10-18 Created: 2023-10-18 Last updated: 2024-01-08Bibliographically approved
Bark, L., Larsson, I.-M., Wallin, E., Simren, J., Zetterberg, H., Lipcsey, M., . . . Hultström, M. (2023). Central nervous system biomarkers GFAp and NfL associate with post-acute cognitive impairment and fatigue following critical COVID-19. Scientific Reports, 13, Article ID 13144.
Open this publication in new window or tab >>Central nervous system biomarkers GFAp and NfL associate with post-acute cognitive impairment and fatigue following critical COVID-19
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2023 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 13, article id 13144Article in journal (Refereed) Published
Abstract [en]

A high proportion of patients with coronavirus disease 2019 (COVID-19) experience post-acute COVID-19, including neuropsychiatric symptoms. Objective signs of central nervous system (CNS) damage can be investigated using CNS biomarkers such as glial fibrillary acidic protein (GFAp), neurofilament light chain (NfL) and total tau (t-tau). We have examined whether CNS biomarkers can predict fatigue and cognitive impairment 3-6 months after discharge from the intensive care unit (ICU) in critically ill COVID-19 patients. Fifty-seven COVID-19 patients admitted to the ICU were included with analysis of CNS biomarkers in blood at the ICU and at follow up. Cognitive dysfunction and fatigue were assessed with the Montreal Cognitive Assessment (MoCA) and the Multidimensional Fatigue inventory (MFI-20). Elevated GFAp at follow-up 3-6 months after ICU discharge was associated to the development of mild cognitive dysfunction (p = 0.01), especially in women (p = 0.005). Patients who experienced different dimensions of fatigue at follow-up had significantly lower GFAp in both the ICU and at follow-up, specifically in general fatigue (p = 0.009), physical fatigue (p = 0.004), mental fatigue (p = 0.001), and reduced motivation (p = 0.001). Women showed a more pronounced decrease in GFAp compared to men, except for in mental fatigue where men showed a more pronounced GFAp decrease compared to women. NfL concentration at follow-up was lower in patients who experienced reduced motivation (p = 0.004). Our findings suggest that GFAp and NfL are associated with neuropsychiatric outcome after critical COVID-19.

Place, publisher, year, edition, pages
Springer Nature, 2023
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-510640 (URN)10.1038/s41598-023-39698-y (DOI)001049345000034 ()37573366 (PubMedID)
Available from: 2023-09-04 Created: 2023-09-04 Last updated: 2023-09-04Bibliographically approved
Stralin, K., Linder, A., Brink, M., Benjaminsson-Nyberg, P., Svefors, J., Bengtsson-Toni, M., . . . Kurland, L. (2023). Design of a national patient-centred clinical pathway for sepsis in Sweden. Infectious Diseases, 55(10), 716-724
Open this publication in new window or tab >>Design of a national patient-centred clinical pathway for sepsis in Sweden
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2023 (English)In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 55, no 10, p. 716-724Article in journal, Editorial material (Other academic) Published
Abstract [en]

Background: The World Health Organization has adopted a resolution on sepsis and urged member states to develop national processes to improve sepsis care. In Sweden, sepsis was selected as one of the ten first diagnoses to be addressed, when the Swedish government in 2019 allocated funds for patient-centred clinical pathways in healthcare. A national multidisciplinary working group, including a patient representative, was appointed to develop the patient-centred clinical pathway for sepsis. Methods: The working group mapped challenges and needs surrounding sepsis care and included a survey sent to all emergency departments (ED) in Sweden, and then designed a patient-centred clinical pathway for sepsis. Results: The working group decided to focus on the following four areas: (1) sepsis alert for early detection and management optimisation for the most severely ill sepsis patients in the ED; (2) accurate sepsis diagnosis coding; (3) structured information to patients at discharge after sepsis care and (4) structured telephone follow-up after sepsis care. A health-economic analysis indicated that the implementation of the clinical pathway for sepsis willmost likely not drive costs. An important aspect of the clinical pathway is implementing continuous monitoring of performance and process indicators. A national working group is currently building up such a systemformonitoring, focusing on extraction of this information from the electronic health records systems. Conclusion: A national patient-centred clinical pathway for sepsis has been developed and is currently being implemented in Swedish healthcare. We believe that the clinical pathway and the accompanying monitoring will provide a more efficient and equal sepsis care and improved possibilities to monitor and further develop sepsis care in Sweden.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2023
Keywords
Sepsis, sepsis alert, clinical pathway, discharge coding, SOFA score, sepsis recovery
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-513066 (URN)10.1080/23744235.2023.2234033 (DOI)001035690300001 ()37477232 (PubMedID)
Available from: 2023-10-06 Created: 2023-10-06 Last updated: 2023-10-06Bibliographically approved
Projects
Immunoinflammation och fibros hos patienter som har pågående eller genomgången svår COVID-19 studerad med positron-emissionstomografi [20210012_HLF]; Uppsala UniversityMECHANISTIC STUDIES OF THE INTRAVASCULAR INNATE IMMUNE SYSTEM (IIIS) IN COVID19 AND ARDS OF OTHER ORIGIN [2021-02252_VR]; Uppsala University; Publications
Lindelöf, L., Rantapää-Dahlqvist, S., Lundtoft, C., Sandling, J. K., Leonard, D., Sayadi, A., . . . Eriksson, O. (2024). A survey of ficolin-3 activity in Systemic Lupus Erythematosus reveals a link to hematological disease manifestations and autoantibody profile. Journal of Autoimmunity, 143, Article ID 103166.
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-1976-4129

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