6 research outputs found
The association of prior paracetamol intake with outcome of very old intensive care patients with COVID-19: results from an international prospective multicentre trial
No full textBACKGROUND: In the early COVID-19 pandemic concerns about the correct choice of analgesics in patients with COVID-19 were raised. Little data was available on potential usefulness or harmfulness of prescription free analgesics, such as paracetamol. This international multicentre study addresses that lack of evidence regarding the usefulness or potential harm of paracetamol intake prior to ICU admission in a setting of COVID-19 disease within a large, prospectively enrolled cohort of critically ill and frail intensive care unit (ICU) patients. METHODS: This prospective international observation study (The COVIP study) recruited ICU patients ≥ 70 years admitted with COVID-19. Data on Sequential Organ Failure Assessment (SOFA) score, prior paracetamol intake within 10 days before admission, ICU therapy, limitations of care and survival during the ICU stay, at 30 days, and 3 months. Paracetamol intake was analysed for associations with ICU-, 30-day- and 3-month-mortality using Kaplan Meier analysis. Furthermore, sensitivity analyses were used to stratify 30-day-mortality in subgroups for patient-specific characteristics using logistic regression. RESULTS: 44% of the 2,646 patients with data recorded regarding paracetamol intake within 10 days prior to ICU admission took paracetamol. There was no difference in age between patients with and without paracetamol intake. Patients taking paracetamol suffered from more co-morbidities, namely diabetes mellitus (43% versus 34%, p < 0.001), arterial hypertension (70% versus 65%, p = 0.006) and had a higher score on Clinical Frailty Scale (CFS; IQR 2–5 versus IQR 2–4, p < 0.001). Patients under prior paracetamol treatment were less often subjected to intubation and vasopressor use, compared to patients without paracetamol intake (65 versus 71%, p < 0.001; 63 versus 69%, p = 0.007). Paracetamol intake was not associated with ICU-, 30-day- and 3-month-mortality, remaining true after multivariate adjusted analysis. CONCLUSION: Paracetamol intake prior to ICU admission was not associated with short-term and 3-month mortality in old, critically ill intensive care patients suffering from COVID-19. Trial registration. This prospective international multicentre study was registered on ClinicalTrials.gov with the identifier “NCT04321265” on March 25, 2020
Contemporary assessment of short- and functional 90-days outcome in old intensive care patients suffering from COVID-19
No full textPurpose: There are limited data about the outcome of old intensive care (ICU) patients suffering from Covid-19 in the post-vaccination era. This study distinguishes the pre- and post-acute illness living conditions of ICU survivors from non-survivors. Methods: This prospective international multicenter study included 642 old (>= 70 years) ICU patients, including data ranging from pre-illness condition to functional 90-days follow-up. The primary endpoint was the difference of living conditions of ICU-survivors before ICU admission and 90-days after ICU discharge. Secondary outcomes were 90-days mortality, and quality of life. Results: A total of 642 patients were included. Significantly more ICU survivors lived at their own homes without support before ICU admission than non-survivors (p = 0.016), while more non-survivors resided in nursing homes (p = 0.016). ICU mortality was 39 %, 30-days and 90 days mortality were 47 %and 55 %. After 90 days, only 22 % maintained the same living conditions. Surviving patients viewed ICU admission positively after 90 days, while relatives were more uncertain. Quality of life indicated a self-reported average score of 60 (50-75). Conclusion: Living conditions influence the outcome of critically ill old patients suffering from Covid-19. Only a minority returned to their initial habitat after ICU survival. Trial registration number NCT04321265Purpose: There are limited data about the outcome of old intensive care (ICU) patients suffering from Covid-19 in the post-vaccination era. This study distinguishes the pre- and post-acute illness living conditions of ICU survivors from non-survivors. Methods: This prospective international multicenter study included 642 old (>= 70 years) ICU patients, including data ranging from pre-illness condition to functional 90-days follow-up. The primary endpoint was the difference of living conditions of ICU-survivors before ICU admission and 90-days after ICU discharge. Secondary outcomes were 90-days mortality, and quality of life. Results: A total of 642 patients were included. Significantly more ICU survivors lived at their own homes without support before ICU admission than non-survivors (p = 0.016), while more non-survivors resided in nursing homes (p = 0.016). ICU mortality was 39 %, 30-days and 90 days mortality were 47 %and 55 %. After 90 days, only 22 % maintained the same living conditions. Surviving patients viewed ICU admission positively after 90 days, while relatives were more uncertain. Quality of life indicated a self-reported average score of 60 (50-75). Conclusion: Living conditions influence the outcome of critically ill old patients suffering from Covid-19. Only a minority returned to their initial habitat after ICU survival. Trial registration number NCT04321265A
In reply: Sex-specific outcomes in COVID-19: missing pieces of the puzzle.
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Search for dark matter and unparticles in events with a Z boson and missing transverse momentum in proton-proton collisions at TeV
No full textA search for dark matter and unparticle production at the LHC has been performed using events containing two charged leptons (electrons or muons), consistent with the decay of a Z boson, and large missing transverse momentum. This study is based on data collected with the CMS detector in 2015, corresponding to an integrated luminosity of 2.3 inverse femtobarns of proton-proton collisions at the LHC, at a center-of-mass energy of 13 TeV. No excess over the standard model expectation is observed. Compared to previous searches in this topology, which exclusively relied on effective field theories, the results are interpreted in terms of a simplified model of dark matter production for both vector and axial vector couplings between a mediator and dark matter particles. The first study of this class of models using CMS data at sqrt(s)=13 TeV is presented. Additionally, effective field theories of dark matter and unparticle production are used to interpret the data
Are circulating immune cells a determinant of pancreatic cancer risk? A prospective study using epigenetic cell count measures
No full textBackground: Evidence is accumulating that immune cells play a prominent role in pancreatic cancer etiology but prospective investigations are missing.
Methods: We conducted a nested case–control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) study with 502 pairs of incident pancreatic cancer cases and matched controls. Relative counts of circulating immune cells (neutrophils and lymphocyte sublineages: total CD3+, CD8+, CD4+, and FOXP3+ regulatory T cells (Tregs) relative to nucleated cells, (white blood cells) were measured by qRT-PCR. ORs with 95% confidence intervals were estimated using logistic regressions, modeling relative counts of immune cells on a continuous scale.
Results: Neither relative counts of immune cell types taken individually, nor mutually adjusted for each other were associated with pancreatic cancer risks. However, in subgroup analyses by strata of lag-time, higher relative counts of Tregs and lower relative counts of CD8+ were significantly associated with an increased pancreatic cancer risks in participants diagnosed within the first 5 years of follow-up.
Conclusions: These results might reflect reverse causation, due to higher relative counts of Tregs and lower counts of CD8+ cells among individuals with more advanced stages of latent pancreatic cancer, who are closer to the point of developing clinical manifest disease.
Impact: We have shown, for the first time, that increased relative counts of regulatory T cells and lower relative counts of CD8+, cytotoxic T cells may be associated with pancreatic cancer risk or relatively late-stage tumor development
Oligogenic analysis across broad phenotypes of 46,XY differences in sex development associated with NR5A1/SF-1 variants : findings from the international SF1next study
No full textBackground Oligogenic inheritance has been suggested as a possible mechanism to explain the broad phenotype observed in individuals with differences of sex development (DSD) harbouring NR5A1/SF-1 variants. Methods We investigated genetic patterns of possible oligogenicity in a cohort of 30 individuals with NR5A1/SF-1 variants and 46,XY DSD recruited from the international SF1next study, using whole exome sequencing (WES) on family trios whenever available. WES data were analysed using a tailored filtering algorithm designed to identify rare variants in DSD and SF-1-related genes. Identified variants were subsequently tested using the Oligogenic Resource for Variant Analysis (ORVAL) bioinformatics platform for a possible combined pathogenicity with the individual NR5A1/SF-1 variant. Findings In 73% (22/30) of the individuals with NR5A1/SF-1 related 46,XY DSD, we identified one to seven additional variants, predominantly in known DSD-related genes, that might contribute to the phenotype. We found identical variants in eight unrelated individuals with DSD in DSD-related genes (e.g., TBCE, FLNB, GLI3 and PDGFRA) and different variants in eight genes frequently associated with DSD (e.g., CDH23, FLNB, GLI2, KAT6B, MYO7A, PKD1, SPRY4 and ZFPM2) in 15 index cases. Our study also identified combinations with NR5A1/SF-1 variants and variants in novel candidate genes. Interpretation These findings highlight the complex genetic landscape of DSD associated with NR5A1/SF-1, where in several cases, the use of advanced genetic testing and filtering with specific algorithms and machine learning tools revealed additional genetic hits that may contribute to the phenotype. Funding Swiss National Science Foundation and Boveri Foundation Zurich. Copyright (c) 2025 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Background Oligogenic inheritance has been suggested as a possible mechanism to explain the broad phenotype observed in individuals with differences of sex development (DSD) harbouring NR5A1/SF-1 variants. Methods We investigated genetic patterns of possible oligogenicity in a cohort of 30 individuals with NR5A1/SF-1 variants and 46,XY DSD recruited from the international SF1next study, using whole exome sequencing (WES) on family trios whenever available. WES data were analysed using a tailored filtering algorithm designed to identify rare variants in DSD and SF-1-related genes. Identified variants were subsequently tested using the Oligogenic Resource for Variant Analysis (ORVAL) bioinformatics platform for a possible combined pathogenicity with the individual NR5A1/SF-1 variant. Findings In 73% (22/30) of the individuals with NR5A1/SF-1 related 46,XY DSD, we identified one to seven additional variants, predominantly in known DSD-related genes, that might contribute to the phenotype. We found identical variants in eight unrelated individuals with DSD in DSD-related genes (e.g., TBCE, FLNB, GLI3 and PDGFRA) and different variants in eight genes frequently associated with DSD (e.g., CDH23, FLNB, GLI2, KAT6B, MYO7A, PKD1, SPRY4 and ZFPM2) in 15 index cases. Our study also identified combinations with NR5A1/SF-1 variants and variants in novel candidate genes. Interpretation These findings highlight the complex genetic landscape of DSD associated with NR5A1/SF-1, where in several cases, the use of advanced genetic testing and filtering with specific algorithms and machine learning tools revealed additional genetic hits that may contribute to the phenotype. Funding Swiss National Science Foundation and Boveri Foundation Zurich. Copyright (c) 2025 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).A
