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Journal of Infectious Diseases, 28.03.2024
Tilføjet 28.03.2024
Abstract Concerns regarding toxicity and resistance of current drugs have been reported in visceral leishmaniasis. Anti-microbial peptides are considered as new promising candidates and amongst them, human cathelicidin hCAP18/LL-37 showed significant parasite killing on drug-sensitive and resistant Leishmania promastigotes, coupled with its apoptosis-inducing role. Administration of hCAP18/LL-37 in infected macrophages also decreased parasite survival and increased the host favorable cytokine IL-12. However, 1,25-dihydroxyvitamin D3 (VitD3)-induced endogenous hCAP18/LL-37 production was hampered in infected THP-1 cells. Infection also suppressed the VitD3-receptor (VDR), transcription factor of hCAP18/LL-37. cAMP response element modulator (CREM), the repressor of VDR, was induced in infection resulting in suppression of both VDR and cathelicidin expression. PGE2/cAMP/PKA axis was found to regulate CREM induction during infection and silencing CREM in infected cells and BALB/c mice led to decreased parasite survival. Present study thus documents the anti-leishmanial potential of cathelicidin and further identifies CREM as a repressor of cathelicidin in Leishmania infection.
Læs mere Tjek på PubMedTulika Munshi, Antima Gupta, Dimitrios Evangelopoulos, Juan David Guzman, Simon Gibbons, Nicholas H. Keep, Sanjib Bhakta
PLoS One Infectious Diseases, 27.03.2024
Tilføjet 27.03.2024
by Tulika Munshi, Antima Gupta, Dimitrios Evangelopoulos, Juan David Guzman, Simon Gibbons, Nicholas H. Keep, Sanjib Bhakta
Læs mere Tjek på PubMedCrowell, Trevor A.; Ritz, Justin; Zheng, Lu; Naqvi, Asma; Cyktor, Joshua C.; Puleo, Joseph; Clagett, Brian; Lama, Javier R.; Kanyama, Cecilia; Little, Susan J.; Cohn, Susan E.; Riddler, Sharon A.; Collier, Ann C.; Heath, Sonya L.; Tantivitayakul, Pornphen; Grinsztejn, Beatriz; Arduino, Roberto C.; Rooney, James F.; van Zyl, Gert U.; Coombs, Robert W.; Fox, Lawrence; Ananworanich, Jintanat; Eron, Joseph J.; Sieg, Scott F.; Mellors, John W.; Daar, Eric S.; for the AIDS Clinical Trials Group (ACTG) A5354/EARLIER Study Team
AIDS, 23.03.2024
Tilføjet 23.03.2024
Objective: To assess how antiretroviral therapy (ART) initiation during acute or early HIV infection (AEHI) affects the viral reservoir and host immune responses. Design: Single-arm trial of ART initiation during AEHI at 30 sites in the Americas, Africa, and Asia. Methods: HIV DNA was measured at week 48 of ART in 5 million CD4+ T cells by sensitive qPCR assays targeting HIV gag and pol. Peripheral blood mononuclear cells were stimulated with potential HIV T cell epitope peptide pools consisting of env, gag, nef, and pol peptides and stained for expression of CD3, CD4, CD8, and intracellular cytokines/chemokines. Results: From 2017 to 2019, 188 participants initiated ART during Fiebig stages I (n = 6), II (n = 43), III (n = 56), IV (n = 23), and V (n = 60). Median age was 27 years (interquartile range 23–38), 27 (14%) participants were female, and 180 (97%) cisgender. Among 154 virally suppressed participants at week 48, 100% had detectable HIV gag or pol DNA. Participants treated during Fiebig I had the lowest HIV DNA levels (P 0.025). At week 48, the magnitude, but not polyfunctionality, of HIV-specific T cell responses was moderately reduced among participants who initiated ART earliest. Conclusion: Earlier ART initiation during AEHI reduced but did not eliminate the persistence of HIV-infected cells in blood. These findings explain the rapid viral rebound observed after ART cessation in early-treated individuals with undetectable HIV DNA by less sensitive methods. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedGrzegorz Dudek, Sebastian Sakowski, Olga Brzezińska, Joanna Sarnik, Tomasz Budlewski, Grzegorz Dragan, Marta Poplawska, Tomasz Poplawski, Michał Bijak, Joanna Makowska
PLoS One Infectious Diseases, 22.03.2024
Tilføjet 22.03.2024
by Grzegorz Dudek, Sebastian Sakowski, Olga Brzezińska, Joanna Sarnik, Tomasz Budlewski, Grzegorz Dragan, Marta Poplawska, Tomasz Poplawski, Michał Bijak, Joanna Makowska Machine learning (ML) algorithms can handle complex genomic data and identify predictive patterns that may not be apparent through traditional statistical methods. They become popular tools for medical applications including prediction, diagnosis or treatment of complex diseases like rheumatoid arthritis (RA). RA is an autoimmune disease in which genetic factors play a major role. Among the most important genetic factors predisposing to the development of this disease and serving as genetic markers are HLA-DRB and non-HLA genes single nucleotide polymorphisms (SNPs). Another marker of RA is the presence of anticitrullinated peptide antibodies (ACPA) which is correlated with severity of RA. We use genetic data of SNPs in four non-HLA genes (PTPN22, STAT4, TRAF1, CD40 and PADI4) to predict the occurrence of ACPA positive RA in the Polish population. This work is a comprehensive comparative analysis, wherein we assess and juxtapose various ML classifiers. Our evaluation encompasses a range of models, including logistic regression, k-nearest neighbors, naïve Bayes, decision tree, boosted trees, multilayer perceptron, and support vector machines. The top-performing models demonstrated closely matched levels of accuracy, each distinguished by its particular strengths. Among these, we highly recommend the use of a decision tree as the foremost choice, given its exceptional performance and interpretability. The sensitivity and specificity of the ML models is about 70% that are satisfying. In addition, we introduce a novel feature importance estimation method characterized by its transparent interpretability and global optimality. This method allows us to thoroughly explore all conceivable combinations of polymorphisms, enabling us to pinpoint those possessing the highest predictive power. Taken together, these findings suggest that non-HLA SNPs allow to determine the group of individuals more prone to develop RA rheumatoid arthritis and further implement more precise preventive approach.
Læs mere Tjek på PubMedIsabel M. BarcelóMaria Escobar-SalomGabriel CabotPau Perelló-BauzàElena Jordana-LluchBiel TaltavullGabriel TorrensEstrella Rojo-MolineroLaura ZamoranoAstrid PérezAntonio OliverCarlos Juan1Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain2Microbiology Department, University Hospital Son Espases (HUSE), Palma, Spain3Centro de Investigación Biomédica en Red, Área Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain4Department of Molecular Biology and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden5National Center for Microbiology, Instituto de Salud Carlos III (ISCIII), Madrid, Spain, Laurent Poirel
Antimicrobial Agents And Chemotherapy, 22.03.2024
Tilføjet 22.03.2024
Clinical Infectious Diseases, 21.03.2024
Tilføjet 21.03.2024
Clinical Infectious Diseases, 21.03.2024
Tilføjet 21.03.2024
Abstract Background Weight gain and associated metabolic complications are increasingly prevalent among people with HIV (PWH). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin-based therapies for diabetes and weight management that have been shown to result in substantial weight loss; however, studies of their effects in PWH are limited.Methods A retrospective single-center cohort study was conducted among PWH who were taking GLP-1RAs at UC San Diego Owen Clinic between 2/1/2021 to 2/1/2023. Baseline clinical data were collected and changes in weight, body mass index (BMI), and hemoglobin A1C (A1C) before starting GLP-1RAs compared to the most recent clinic visit were calculated (with a minimum of 3 months follow-up time required). Logistic regression was performed to identify variables associated with >5% of total body weight loss.Results A total of 225 patients received on average 13 months of GLP-1RA therapy, with 85 (37.8%) achieving the maximum GLP-1RA dose. GLP-1RA therapy resulted, on average, in a loss of 5.4 kg, decrease in BMI by 1.8 kg/m2, and decrease in A1C by 0.6%. In the multivariable analysis, higher baseline BMI [OR 1.10 (1.03-1.16)], treatment duration of GLP-1RA therapy greater than 6 months [OR 3.12 (1.49-6.49], and use of tirzepatide [OR 5.46 (1.44-20.76)] were significantly more likely to be associated with >5% weight loss.Conclusions Use of GLP-1RAs led to declines in weight, BMI, and hemoglobin A1C among PWH and offers an additional strategy to address weight gain and diabetes.
Læs mere Tjek på PubMedClinical Infectious Diseases, 19.03.2024
Tilføjet 19.03.2024
Somayaji, R., Luke, D. R., Lau, A., Guner, R., Tabak, O. F., Hepokoski, M., Gardetto, N., Conrad, S. A., Kumar, S. D., Ghosh, K., Robbins, S. M., Senger, D. L., Sun, D., Lim, R. K. S., Liu, J., Eser, F., Karaali, R., Tremblay, A., Muruve, D.
BMJ Open, 15.03.2024
Tilføjet 15.03.2024
ObjectiveDipeptidase-1 (DPEP-1) is a recently discovered leucocyte adhesion receptor for neutrophils and monocytes in the lungs and kidneys and serves as a potential therapeutic target to attenuate inflammation in moderate-to-severe COVID-19. We aimed to evaluate the safety and efficacy of the DPEP-1 inhibitor, LSALT peptide, to prevent specific organ dysfunction in patients hospitalised with COVID-19. DesignPhase 2a randomised, placebo-controlled, double-blinded, trial. SettingHospitals in Canada, Turkey and the USA. ParticipantsA total of 61 subjects with moderate-to-severe COVID-19. InterventionsRandomisation to LSALT peptide 5 mg intravenously daily or placebo for up to 14 days. Primary and secondary outcome measuresThe primary endpoint was the proportion of subjects alive and free of respiratory failure and/or the need for renal replacement therapy (RRT). Numerous secondary and exploratory endpoints were assessed including ventilation-free days, and changes in kidney function or serum biomarkers. ResultsAt 28 days, 27 (90.3%) and 28 (93.3%) of subjects in the placebo and LSALT groups were free of respiratory failure and the need for RRT (p=0.86). On days 14 and 28, the number of patients still requiring more intensive respiratory support (O2 ≥6 L/minute, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation) was 6 (19.4%) and 3 (9.7%) in the placebo group versus 2 (6.7%) and 2 (6.7%) in the LSALT group, respectively (p=0.14; p=0.67). Unadjusted analysis of ventilation-free days demonstrated 22.8 days for the LSALT group compared with 20.9 in the placebo group (p=0.4). LSALT-treated subjects had a significant reduction in the fold expression from baseline to end of treatment of serum CXCL10 compared with placebo (p=0.02). Treatment-emergent adverse events were similar between groups. ConclusionIn a Phase 2 study, LSALT peptide was demonstrated to be safe and tolerated in patients hospitalised with moderate-to-severe COVID-19. Trial registration numberNCT04402957.
Læs mere Tjek på PubMedSomayaji, R., Luke, D. R., Lau, A., Guner, R., Tabak, O. F., Hepokoski, M., Gardetto, N., Conrad, S. A., Kumar, S. D., Ghosh, K., Robbins, S. M., Senger, D. L., Sun, D., Lim, R. K. S., Liu, J., Eser, F., Karaali, R., Tremblay, A., Muruve, D.
BMJ Open, 15.03.2024
Tilføjet 15.03.2024
ObjectiveDipeptidase-1 (DPEP-1) is a recently discovered leucocyte adhesion receptor for neutrophils and monocytes in the lungs and kidneys and serves as a potential therapeutic target to attenuate inflammation in moderate-to-severe COVID-19. We aimed to evaluate the safety and efficacy of the DPEP-1 inhibitor, LSALT peptide, to prevent specific organ dysfunction in patients hospitalised with COVID-19. DesignPhase 2a randomised, placebo-controlled, double-blinded, trial. SettingHospitals in Canada, Turkey and the USA. ParticipantsA total of 61 subjects with moderate-to-severe COVID-19. InterventionsRandomisation to LSALT peptide 5 mg intravenously daily or placebo for up to 14 days. Primary and secondary outcome measuresThe primary endpoint was the proportion of subjects alive and free of respiratory failure and/or the need for renal replacement therapy (RRT). Numerous secondary and exploratory endpoints were assessed including ventilation-free days, and changes in kidney function or serum biomarkers. ResultsAt 28 days, 27 (90.3%) and 28 (93.3%) of subjects in the placebo and LSALT groups were free of respiratory failure and the need for RRT (p=0.86). On days 14 and 28, the number of patients still requiring more intensive respiratory support (O2 ≥6 L/minute, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation) was 6 (19.4%) and 3 (9.7%) in the placebo group versus 2 (6.7%) and 2 (6.7%) in the LSALT group, respectively (p=0.14; p=0.67). Unadjusted analysis of ventilation-free days demonstrated 22.8 days for the LSALT group compared with 20.9 in the placebo group (p=0.4). LSALT-treated subjects had a significant reduction in the fold expression from baseline to end of treatment of serum CXCL10 compared with placebo (p=0.02). Treatment-emergent adverse events were similar between groups. ConclusionIn a Phase 2 study, LSALT peptide was demonstrated to be safe and tolerated in patients hospitalised with moderate-to-severe COVID-19. Trial registration numberNCT04402957.
Læs mere Tjek på PubMedSomayaji, R., Luke, D. R., Lau, A., Guner, R., Tabak, O. F., Hepokoski, M., Gardetto, N., Conrad, S. A., Kumar, S. D., Ghosh, K., Robbins, S. M., Senger, D. L., Sun, D., Lim, R. K. S., Liu, J., Eser, F., Karaali, R., Tremblay, A., Muruve, D.
BMJ Open, 15.03.2024
Tilføjet 15.03.2024
ObjectiveDipeptidase-1 (DPEP-1) is a recently discovered leucocyte adhesion receptor for neutrophils and monocytes in the lungs and kidneys and serves as a potential therapeutic target to attenuate inflammation in moderate-to-severe COVID-19. We aimed to evaluate the safety and efficacy of the DPEP-1 inhibitor, LSALT peptide, to prevent specific organ dysfunction in patients hospitalised with COVID-19. DesignPhase 2a randomised, placebo-controlled, double-blinded, trial. SettingHospitals in Canada, Turkey and the USA. ParticipantsA total of 61 subjects with moderate-to-severe COVID-19. InterventionsRandomisation to LSALT peptide 5 mg intravenously daily or placebo for up to 14 days. Primary and secondary outcome measuresThe primary endpoint was the proportion of subjects alive and free of respiratory failure and/or the need for renal replacement therapy (RRT). Numerous secondary and exploratory endpoints were assessed including ventilation-free days, and changes in kidney function or serum biomarkers. ResultsAt 28 days, 27 (90.3%) and 28 (93.3%) of subjects in the placebo and LSALT groups were free of respiratory failure and the need for RRT (p=0.86). On days 14 and 28, the number of patients still requiring more intensive respiratory support (O2 ≥6 L/minute, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation) was 6 (19.4%) and 3 (9.7%) in the placebo group versus 2 (6.7%) and 2 (6.7%) in the LSALT group, respectively (p=0.14; p=0.67). Unadjusted analysis of ventilation-free days demonstrated 22.8 days for the LSALT group compared with 20.9 in the placebo group (p=0.4). LSALT-treated subjects had a significant reduction in the fold expression from baseline to end of treatment of serum CXCL10 compared with placebo (p=0.02). Treatment-emergent adverse events were similar between groups. ConclusionIn a Phase 2 study, LSALT peptide was demonstrated to be safe and tolerated in patients hospitalised with moderate-to-severe COVID-19. Trial registration numberNCT04402957.
Læs mere Tjek på PubMedClinical Infectious Diseases, 14.03.2024
Tilføjet 14.03.2024
Abstract Background A next-generation Vero cell rabies vaccine (PVRV-NG2) was developed using the same Pitman–Moore strain as in the licensed purified Vero cell vaccine (PVRV; Verorab®) and the human diploid cell vaccine (HDCV; Imovax Rabies®).Methods This dual-center, modified double-blind, phase III study in France evaluated immunogenic non-inferiority and safety of PVRV-NG2 with and without concomitant intramuscular human rabies immunoglobulin (HRIG), compared with PVRV+HRIG and HDCV+HRIG, in a simulated post-exposure prophylaxis (PEP) regimen. Healthy adults ≥18 years old (N=640) were randomized 3:1:1:1 to receive PVRV-NG2+HRIG, PVRV+HRIG, HDCV+HRIG, or PVRV-NG2 alone (administered as single vaccine injections on days [D] 0, 3, 7, 14, and 28, with HRIG administered on D0 in applicable groups). Rabies virus neutralizing antibodies (RVNA titers) were assessed pre- (D0) and post-vaccination (D14, D28, and D42) using the rapid fluorescent focus inhibition test. Non-inferiority, based on the proportion of participants achieving RVNA titers ≥0.5 IU/mL (primary objective), was demonstrated if the lower limit of the 95% CI of the difference in proportions between PVRV-NG2+HRIG and PVRV+HRIG/HDCV+HRIG was >−5% at D28. Safety was assessed up to 6 months after the last injection.Results The non-inferiority of PVRV-NG2+HRIG, compared with PVRV+HRIG and HDCV+HRIG, was demonstrated. Nearly all participants (99.6%, PVRV-NG2+HRIG; 100%, PVRV+HRIG; 98.7%, HDCV+HRIG; 100%, PVRV-NG2 alone) achieved RVNA titers ≥0.5 IU/mL at D28. Geometric mean titers were similar between groups with concomitant HRIG administration at all time points. Safety profiles were similar between PVRV-NG2 and comparator vaccines.Conclusions In a simulated PEP setting, PVRV-NG2+HRIG showed comparable immunogenicity and safety to current standard-of-care vaccines.Clinical Trials Registration NCT03965962.
Læs mere Tjek på PubMedMalaria Journal, 14.03.2024
Tilføjet 14.03.2024
Abstract Background The Great Mekong Subregion has attained a major decline in malaria cases and fatalities over the last years, but residual transmission hotspots remain, supposedly fueled by forest workers and migrant populations. This study aimed to: (i) characterize the fine-scale mobility of forest-goers and understand links between their daily movement patterns and malaria transmission, using parasites detection via real time polymerase chain reaction (RT PCR) and the individual exposure to Anopheles bites by quantification of anti-Anopheles saliva antibodies via enzyme-linked immunosorbent assay; (ii) assess the concordance of questionnaires and Global Positioning System (GPS) data loggers for measuring mobility. Methods Two 28 day follow-ups during dry and rainy seasons, including a GPS tracking, questionnaires and health examinations, were performed on male forest goers representing the population at highest risk of infection. Their time spent in different land use categories and demographic data were analyzed in order to understand the risk factors driving malaria in the study area. Results Malaria risk varied with village forest cover and at a resolution of only a few kilometers: participants from villages outside the forest had the highest malaria prevalence compared to participants from forest fringe’s villages. The time spent in a specific environment did not modulate the risk of malaria, in particular the time spent in forest was not associated with a higher probability to detect malaria among forest-goers. The levels of antibody response to Anopheles salivary peptide among participants were significantly higher during the rainy season, in accordance with Anopheles mosquito density variation, but was not affected by sociodemographic and mobility factors. The agreement between GPS and self-reported data was only 61.9% in reporting each kind of visited environment. Conclusions In a context of residual malaria transmission which was mainly depicted by P. vivax asymptomatic infections, the implementation of questionnaires, GPS data-loggers and quantification of anti-saliva Anopheles antibodies on the high-risk group were not powerful enough to detect malaria risk factors associated with different mobility behaviours or time spent in various environments. The joint implementation of GPS trackers and questionnaires allowed to highlight the limitations of both methodologies and the benefits of using them together. New detection and follow-up strategies are still called for.
Læs mere Tjek på PubMedJi Woong Kim, Ji Hyun Lee, Hyun Jung Kim, Kyun Heo, Yoonwoo Lee, Hui Jeong Jang, Ho‐Young Lee, Jun Won Park, Yea Bin Cho, Ha Gyeong Shin, Ha Rim Yang, Hee Eon Lee, Jin Young Song, Sukmook Lee
Journal of Medical Virology, 7.03.2024
Tilføjet 7.03.2024
Zhiyi LiaoChaoming WangXiaopeng TangMengli YangZilei DuanLei LiuShuaiyao LuLei MaRuomei ChengGan WangHongqi LiuShuo YangJingwen XuDawit Adisu TadeseJames MwangiPeter Muiruri KamauZhiye ZhangLian YangGuoyang LiaoXudong ZhaoXiaozhong PengRen LaiaEngineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology-Chinese University of Hong Kong Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), and Sino-African Joint Research Center, New Cornerstone Science Laboratory, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming 650201, ChinabKunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, ChinacSchool of Basic Medicine, Qingdao University, Qingdao 266071, ChinadInstitute of Medical Biology, Chinese Academy of Medical Sciences, Kunming 650118, ChinaeLaboratory of Animal Tumor Models, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, ChinafKunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, China
Proceedings of the National Academy of Sciences, 6.03.2024
Tilføjet 6.03.2024
Proceedings of the National Academy of Sciences, Volume 121, Issue 10, March 2024.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 5.03.2024
Tilføjet 5.03.2024
Abstract We previously described a novel Plasmodium vivax invasion mechanism into human reticulocytes via the PvRBP2a-CD98 receptor-ligand pair. We assessed the PvRBP2a epitopes involved in CD98 binding and recognised by antibodies from infected patients using linear epitope mapping. We identified two epitope clusters mediating PvRBP2a-CD98 interaction. One cluster named cluster B (PvRBP2a431-448, TAALKEKGKLLANLYNKL) was the target of antibody responses in P. vivax-infected humans. Peptides from each cluster were able to prevent live parasite invasion of human reticulocytes. These results provide new insights for development of a malaria blood stage vaccine against P. vivax.
Læs mere Tjek på PubMedWiseman, Robyn L.; Bigos, Kristin L.; Dastgheyb, Raha M.; Barker, Peter B.; Rubin, Leah H.; Slusher, Barbara S.
AIDS, 2.03.2024
Tilføjet 2.03.2024
Objectives : Cognitive impairment persists in virally-suppressed people with HIV (VS-PWH) especially in higher order domains. One cortical circuit, linked to these domains, is regulated by N-acetyl-aspartyl glutamate (NAAG), the endogenous agonist of the metabotropic glutamate receptor 3. The enzyme glutamate carboxypeptidase II (GCPII) catabolizes NAAG and is upregulated in aging and disease. Inhibition of GCPII increases brain NAAG and improves learning and memory in rodent and primate models. Design: As higher-order cognitive impairment is present in VS-PWH, and NAAG has not been investigated in earlier magnetic resonance spectroscopy studies (MRS), we investigated if brain NAAG levels measured by MRS were associated with cognitive function. Methods: We conducted a retrospective analysis of 7-Tesla MRS data from a previously published study on cognition in older VS-PWH. The original study did not separately quantify NAAG, therefore work for this report focused on relationships between regional NAAG levels in frontal white matter (FWM), left hippocampus, left basal ganglia and domain-specific cognitive performance in 40 VS-PWH after adjusting for confounds. Participants were >50 years of age, negative for affective and neurologic disorders, and had no prior 3-month psychoactive-substance use. Results: Higher NAAG levels in FWM were associated with better attention/working memory. Higher left basal ganglia NAAG related to better verbal fluency. There was a positive relationship between hippocampal NAAG and executive function which lost significance after correction for confounds. Conclusions: These data suggest brain NAAG serves as a biomarker of cognition in VS-PWH. Pharmacological modulation of brain NAAG warrants investigation as a therapeutic approach for cognitive deficits in VS-PWH. Conclusions: These data suggest brain NAAG serves as a biomarker of cognition in VS-PWH. Pharmacological modulation of brain NAAG warrants investigation as a therapeutic approach for cognitive deficits in VS-PWH. Graphical_abstract http://links.lww.com/QAD/D137 Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
Læs mere Tjek på PubMedMiao ZhangBingqing YangJingru ShiZhiqiang WangYuan Liu1Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, China2Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, China3Institute of Comparative Medicine, Yangzhou University, Yangzhou, China, Anne-Catrin Uhlemann
Antimicrobial Agents And Chemotherapy, 29.02.2024
Tilføjet 29.02.2024
Charanpreet Kaur, Kandala Pavan Asrith, S. G. Ramachandra, Nagendra R. Hegde
PLoS One Infectious Diseases, 28.02.2024
Tilføjet 28.02.2024
by Charanpreet Kaur, Kandala Pavan Asrith, S. G. Ramachandra, Nagendra R. Hegde Subclinical infection of laboratory animals with one or more of several pathogens affects the results of experiments on animals. Monitoring the health of laboratory animals encompasses routine surveillance for pathogens, including several viruses. This study aimed to explore the development of an alternative assay to the existing ones for detecting infection of mice and rats with the parvoviruses minute virus of mice (MVM) and Kilham rat virus (KRV), respectively. Full-length VP2 and NS1 proteins of these parvoviruses, besides fragments containing multiple predicted epitopes stitched together, were studied for serological detection. The optimal dilution of full-length proteins and antigenic regions containing predicted epitopes for coating, test sera, and conjugate was determined using a checkerboard titration at each step. The assays were evaluated vis-à-vis commercially available ELISA kits. The results showed that an engineered fusion of fragments containing multiple predicted MVM VP2 and NS1 epitopes was better than either of the full-length proteins for detecting antibodies in 90% of the tested sera samples. For KRV ELISA, full-length VP2 was better compared to other individual recombinant protein fragments or combinations thereof for the detection of antibodies in sera. This report is the first description of an ELISA for KRV and an improved assay for MVM. Importantly, our assays could be exploited with small volumes of sera. The results also demonstrate the utility of immunoinformatics-driven polypeptide engineering in the development of diagnostic assays and the potential to develop better tests for monitoring the health status of laboratory animals.
Læs mere Tjek på PubMedAndrew MulatoEric LansdonRon AoyamaJohannes VoigtMichael LeeAlbert LiclicanGary LeeEric SingerBrian StaffordRuoyu GongBernard MurrayJulie ChanJohnny LeeYili XuShekeba AhmadyarAna GonzalezAesop ChoGeorge J. StepanUli SchmitzBrian SchultzBruno MarchandBoris BrumshteinRuth WangHelen YuTomas CihlarLianhong XuStephen R. Yant1Department of Virology, Gilead Sciences, Foster City, California, USA2Department of Structural Biology and Chemistry, Gilead Sciences, Foster City, California, USA3Department of Drug Metabolism, Gilead Sciences, Foster City, California, USA4Department of Discovery Sciences and Technology, Gilead Sciences, Foster City, California, USA5Department of Medicinal Chemistry, Gilead Sciences, Foster City, California, USA, Miguel Angel Martinez
Antimicrobial Agents And Chemotherapy, 22.02.2024
Tilføjet 22.02.2024
Chris Kenyon
International Journal of Infectious Diseases, 21.02.2024
Tilføjet 21.02.2024
Three randomized controlled trials have found that doxycycline post exposure prophylaxis (doxy-PEP) can reduce the incidence of gonorrhoea, chlamydia and syphilis in men who have sex with men (MSM) [1]. As a result, a number of international organizations suggest that doxy-PEP should be considered for use by MSM at risk [1].
Læs mere Tjek på PubMedBMC Infectious Diseases, 21.02.2024
Tilføjet 21.02.2024
Abstract Background Leprosy is an infectious disease with a slow decline in global annual caseload in the past two decades. Active case finding and post-exposure prophylaxis (PEP) with a single dose of rifampicin (SDR) are recommended by the World Health Organization as measures for leprosy elimination. However, more potent PEP regimens are needed to increase the effect in groups highest at risk (i.e., household members and blood relatives, especially of multibacillary patients). The PEP++ trial will assess the effectiveness of an enhanced preventive regimen against leprosy in high-endemic districts in India, Brazil, Bangladesh, and Nepal compared with SDR-PEP. Methods The PEP++ study is a cluster-randomised controlled trial in selected districts of India, Brazil, Bangladesh, and Nepal. Sub-districts will be allocated randomly to the intervention and control arms. Leprosy patients detected from 2015 − 22 living in the districts will be approached to list their close contacts for enrolment in the study. All consenting participants will be screened for signs and symptoms of leprosy and tuberculosis (TB). In the intervention arm, eligible contacts receive the enhanced PEP++ regimen with three doses of rifampicin (150 − 600 mg) and clarithromycin (150 − 500 mg) administered at four-weekly intervals, whereas those in the control arm receive SDR-PEP. Follow-up screening for leprosy will be done for each individual two years after the final dose is administered. Cox’ proportion hazards analysis and Poisson regression will be used to compare the incidence rate ratios between the intervention and control areas as the primary study outcome. Discussion Past studies have shown that the level of SDR-PEP effectiveness is not uniform across contexts or in relation to leprosy patients. To address this, a number of recent trials are seeking to strengthen PEP regimens either through the use of new medications or by increasing the dosage of the existing ones. However, few studies focus on the impact of multiple doses of chemoprophylaxis using a combination of antibiotics. The PEP++ trial will investigate effectiveness of both an enhanced regimen and use geospatial analysis for PEP administration in the study communities. Trial registration NL7022 on the Dutch Trial Register on April 12, 2018. Protocol version 9.0 updated on 18 August 2022 https://www.onderzoekmetmensen.nl/en/trial/23060
Læs mere Tjek på PubMedJournal of Infectious Diseases, 20.02.2024
Tilføjet 20.02.2024
Abstract Background Lysins (cell wall hydrolases) targeting Gram-negative organisms require engineering to permeabilize the outer membrane and access subjacent peptidoglycan to facilitate killing. In the current study, the potential clinical utility for engineered lysin, CF-370, was examined in vitro and in vivo against Gram-negative pathogens important in human infections.Methods MICs and bactericidal activity were determined using standard methods. An in vivo proof-of-concept efficacy study was conducted using a rabbit acute pneumonia model caused by Pseudomonas aeruginosa.Results CF-370 exhibited potent antimicrobial activity, with MIC50/90 values (in µg/mL) for: P. aeruginosa, 1/2; Acinetobacter baumannii, 1/1; Escherichia coli, 0.25/1; Klebsiella pneumoniae, 2/4; Enterobacter cloacae 1/4; and Stenotrophomonas maltophilia 2/8. CF-370 furthermore demonstrated: i) bactericidal activity; (ii) activity in serum; iii) a low propensity for resistance; iv) anti-biofilm activity; and v) synergy with antibiotics. In the pneumonia model, CF-370 alone decreased bacterial densities in lungs, kidneys and spleen vs. vehicle control, and demonstrated significantly increased efficacy when combined with meropenem (vs either agent alone).Conclusions CF-370 is the first engineered lysin described with potent broad spectrum in vitro activity against multiple clinically-relevant Gram-negative pathogens, as well as potent in vivo efficacy in an animal model of severe invasive multi-system infection.
Læs mere Tjek på PubMedBolanaki, Myrto; Winning, Johannes; Slagman, Anna; Lehmann, Thomas; Kiehntopf, Michael; Stacke, Angelika; Neumann, Caroline; Reinhart, Konrad; Möckel, Martin; Bauer, Michael
Critical Care Medicine, 15.02.2024
Tilføjet 15.02.2024
Objectives: Consensus regarding biomarkers for detection of infection-related organ dysfunction in the emergency department is lacking. We aimed to identify and validate biomarkers that could improve risk prediction for overt or incipient organ dysfunction when added to quick Sepsis-related Organ Failure Assessment (qSOFA) as a screening tool. Design: In a large prospective multicenter cohort of adult patients presenting to the emergency department with a qSOFA score greater than or equal to 1, admission plasma levels of C-reactive protein, procalcitonin, adrenomedullin (either bioavailable adrenomedullin or midregional fragment of proadrenomedullin), proenkephalin, and dipeptidyl peptidase 3 were assessed. Least absolute shrinkage and selection operator regression was applied to assess the impact of these biomarkers alone or in combination to detect the primary endpoint of prediction of sepsis within 96 hours of admission. Setting: Three tertiary emergency departments at German University Hospitals (Jena University Hospital and two sites of the Charité University Hospital, Berlin). Patients: One thousand four hundred seventy-seven adult patients presenting with suspected organ dysfunction based on qSOFA score greater than or equal to 1. Interventions: None. Measurements and Main Results: The cohort was of moderate severity with 81% presenting with qSOFA = 1; 29.2% of these patients developed sepsis. Procalcitonin outperformed all other biomarkers regarding the primary endpoint (area under the curve for receiver operating characteristic [AUC-ROC], 0.86 [0.79–0.93]). Adding other biomarkers failed to further improve the AUC-ROC for the primary endpoint; however, they improved the model regarding several secondary endpoints, such as mortality, need for vasopressors, or dialysis. Addition of procalcitonin with a cutoff level of 0.25 ng/mL improved net (re)classification by 35.2% compared with qSOFA alone, with positive and negative predictive values of 60.7% and 88.7%, respectively. Conclusions: Biomarkers of infection and organ dysfunction, most notably procalcitonin, substantially improve early prediction of sepsis with added value to qSOFA alone as a simple screening tool on emergency department admission.
Læs mere Tjek på PubMedBMC Infectious Diseases, 14.02.2024
Tilføjet 14.02.2024
Abstract Background Food borne diseases is a challenging problem nowadays. Salmonella and Shigella species are great concern of food-born outbreaks. Thus, this study was aimed to assess the prevalence, antimicrobial susceptibility test and associated factors of Salmonella and Shigella species in fruit juices and salads. Methods A community based cross sectional study design was carried out on 50 juice houses from December to March 2020 in Mekelle. One hundred fifty samples were collected aseptically from the juice houses for laboratory analysis. Information related to risk factors was obtained using a structured questionnaire. In the laboratory, samples were homogenized using peptone water and incubated overnight for enrichment. Then, Salmonella and Shigella species were isolated on Salmonella-Shigella agar and Xylose Lysine Deoxycholate agar. Disc diffusion method was used to perform antimicrobial susceptibility test. Using SPSS (version 22) package, descriptive statistics and Chi square test (χ2) were used to analyze the data, and p
Læs mere Tjek på PubMedGroele, L., Dzygało, K., Kowalska, A., Szypowska, A.
BMJ Open, 10.02.2024
Tilføjet 10.02.2024
IntroductionSphingolipids regulate proinsulin folding, insulin secretion and control beta cells apoptosis. Recent evidence has demonstrated that, among other factors, reduced amounts of sulfatide may be relevant in the development of type 1 diabetes (T1D). Thus, fenofibrate, which activates sulfatide biosynthesis, may prolong remission in subjects with T1D. The aim of the study is to evaluate clinical efficacy of fenofibrate on the maintenance of residual beta-cell function in children with newly diagnosed T1D. Methods and analysisA total of 102 children aged 10–17 years with newly diagnosed T1D will be enrolled in a double-blind, two-centre randomised, non-commercial, placebo-controlled trial. Subjects who will meet all inclusion criteria will be randomly assigned to receive fenofibrate at a dose of 160 mg or an identically appearing placebo, orally, once daily, for 12 months. The primary endpoint will be the area under the curve of the C-peptide level during 2-hour responses to a mixed-meal tolerance test (MMTT). Secondary endpoints include fasting and maximum C-peptide concentration in the MMTT, parameters of diabetes control and glucose fluctuations, daily insulin requirement, inflammation markers, genetic analysis, safety and tolerance of the fenofibrate Ethics and disseminationThe study protocol was approved by the Bioethics Committee. The results of this study will be submitted to a peer-reviewed diabetic journal. Abstracts will be submitted to international and national conferences. Trial registration numberEnduraCT 2020-003916-28.
Læs mere Tjek på PubMedClinical Infectious Diseases, 10.02.2024
Tilføjet 10.02.2024
Abstract Over the past two decades, cases of sexually transmitted infections (STIs) due to syphilis, gonorrhea, and chlamydia have been rising in the United States, disproportionately among gay, bisexual, and other men who have sex with men (MSM), as well as racial and ethnic minorities of all genders. In this review, we address updates about the evidence on doxycycline post-exposure prophylaxis (doxy-PEP) for prevention of bacterial STIs, including efficacy, safety, antimicrobial resistance (AMR), acceptability, modeling population impact, and evolving guidelines for use. Equitable implementation of doxy-PEP will require evaluation of who is offered and initiates it, understanding patterns of use and longer-term STI incidence and AMR, provider training, and tailored community education.
Læs mere Tjek på PubMedTomáš Scholz, Nadav Davidovich
Trends in Parasitology, 9.02.2024
Tilføjet 9.02.2024
The tapeworm Amirthalingamia macracantha is a parasite of African cormorants whose larvae infect tilapia and other cichlids. Tilapia are the second most important group of farmed fish worldwide. Over the course of a few years, this parasite has successfully spread to the Middle East, infecting fish and bird populations there. This is a unique example of accelerated spillover (‘pathogen pollution’) of an alien parasite with a complex life cycle involving three hosts (copepods – fish – birds). Considering the size of the larvae (up to 2 cm) and their localisation in the liver, this parasite poses a potential threat to local communities of wild, endangered cichlids and farmed tilapia.
Læs mere Tjek på PubMedJulián Fernando Oviedo-León, Maribel Cornejo-Mazón, Rosario Ortiz-Hernández, Nayeli Torres-Ramírez, Humberto Hernández-Sánchez, Diana C. Castro-Rodríguez
PLoS One Infectious Diseases, 7.02.2024
Tilføjet 7.02.2024
by Julián Fernando Oviedo-León, Maribel Cornejo-Mazón, Rosario Ortiz-Hernández, Nayeli Torres-Ramírez, Humberto Hernández-Sánchez, Diana C. Castro-Rodríguez Due to the distinctive characteristics of probiotics, it is essential to pinpoint strains originating from diverse sources that prove efficacious in addressing a range of pathologies linked to dysfunction of the intestinal barrier. Nine strains of lactic acid bacteria were isolated from two different sources of tepache kefir grains (KAS2, KAS3, KAS4, KAS7, KAL4, KBS2, KBS3, KBL1 and KBL3), and were categorized to the genus Lacticaseibacillus, Liquorilactobacillus, and Lentilactobacillus by 16S rRNA gene. Kinetic behaviors of these strains were evaluated in MRS medium, and their probiotic potential was performed: resistance to low pH, tolerance to pepsin, pancreatin, bile salts, antibiotic resistance, hemolytic activity, and adhesion ability. KAS7 strain presented a higher growth rate (0.50 h-1) compared with KAS2 strain, who presented a lower growth rate (0.29 h-1). KBS2 strain was the only strain that survived the in vitro stomach simulation conditions (29.3%). Strain KBL1 demonstrated significantly higher viability (90.6%) in the in vitro intestine simulation conditions. Strain KAS2 demonstrated strong hydrophilic character with chloroform (85.6%) and xylol (57.6%) and a higher percentage of mucin adhesion (87.1%). However, strains KBS2 (84.8%) and KBL3 (89.5%) showed the highest autoaggregation values. In terms of adhesion to the intestinal epithelium in rats, strains KAS2, KAS3 and KAS4 showed values above 80%. The growth of the strains KAS2, KAS3, KAS4, KBS2, and KBL3 was inhibited by cefuroxime, cefotaxime, tetracycline, ampicillin, erythromycin, and cephalothin. Strains KBS2 (41.9% and 33.5%) and KBL3 (42.5% and 32.8%) had the highest co-aggregation values with S. aureus and E. coli. The results obtained in this study indicate that lactic acid bacteria isolated from tepache can be considered as candidates for potentially probiotic bacteria, laying the foundations to evaluate their probiotic functionality in vivo and thus to be used in the formulation of functional foods.
Læs mere Tjek på PubMedJoshua Osowicki, Fergus Hamilton, Todd C. Lee, Michael Marks, Erin K. McCreary, Emily G. McDonald, Jonathan H. Ryder, Steven YC. Tong
Clinical Microbiology and Infection, 7.02.2024
Tilføjet 7.02.2024
The spectre of severe invasive infections caused by Streptococcus pyogenes and Staphylococcus aureus haunt clinicians and patients alike. They are the quintessential causes of devastating high profile ‘front page sepsis’ cases affecting children and adults, often without recognised risk factors, and typically associated with toxic shock syndromes (TSS) and necrotizing soft tissue infections (NSTI), as seen in the global surge of invasive S. pyogenes disease from late 2022.(1) These fulminant clinical syndromes demand rapid empiric antibiotic treatment and urgent surgical intervention for source control.
Læs mere Tjek på PubMedYue ZhangVanthana BharathiTatsuya DokoshiJaime de AndaLauryn Tumey UrseryNikhil N. KulkarniYoshiyuki NakamuraJonathan ChenElizabeth W. C. LuoLamei WangHua XuAlison CoadyRaymond ZurichMichelle W. LeeTsutomu MatsuiHongKyu LeeLiana C. ChanAthena A. SchepmoesMary S. LiptonRui ZhaoJoshua N. AdkinsGeremy C. ClairLance R. ThurlowJonathan C. SchislerMatthew C. WolfgangRobert S. HaganMichael R. YeamanThomas M. WeissXinhua ChenMelody M. H. LiVictor NizetSilvio AntoniakNigel MackmanRichard L. GalloGerard C. L. WongaDepartment of Bioengineering, University of California, Los Angeles, CA 90095bDepartment of Chemistry and Biochemistry, University of California, Los Angeles, CA 9009cCalifornia NanoSystems Institute, University of California, Los Angeles, CA 90095dDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA 90095eBiomedical Engineering, School of Engineering, Westlake University, Hangzhou, Zhejiang 310012, ChinafUniversity of North Carolina Blood Research Center, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599gDepartment of Dermatology, University of California San Diego, La Jolla, CA 92093hDivision of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215iDepartment of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA 92093jStanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Stanford University, Menlo Park, CA 94025kDivision of Molecular Medicine, Harbor-University of California Los Angeles Medical Center, Los Angeles County, Torrance, CA 90502lDivision of Infectious Diseases, Harbor-University of California Los Angeles Medical Center, Los Angeles County, Torrance, CA 90502mDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095nInstitute for Infection & Immunity, Lundquist Institute for Biomedical Innovation, Harbor-University of California Los Angeles Medical Center, Torrance, CA 90502oEnvironmental Molecular Science Division, Pacific Northwest National Laboratory, Richland, WA 99354pBiological Science Division, Pacific Northwest National Laboratory, Richland, WA 99354qDivision of Oral and Craniofacial Health Sciences, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599rDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599sMcAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599tDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599uComputational Medicine Program, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599vMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599wDivision of Pulmonary Diseases and Critical Care Medicine, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599xDepartment of Pathology and Laboratory Medicine, University of North Carolina Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
Proceedings of the National Academy of Sciences, 7.02.2024
Tilføjet 7.02.2024
Proceedings of the National Academy of Sciences, Volume 121, Issue 6, February 2024.
Læs mere Tjek på PubMedYue ZhangVanthana BharathiTatsuya DokoshiJaime de AndaLauryn Tumey UrseryNikhil N. KulkarniYoshiyuki NakamuraJonathan ChenElizabeth W. C. LuoLamei WangHua XuAlison CoadyRaymond ZurichMichelle W. LeeTsutomu MatsuiHongKyu LeeLiana C. ChanAthena A. SchepmoesMary S. LiptonRui ZhaoJoshua N. AdkinsGeremy C. ClairLance R. ThurlowJonathan C. SchislerMatthew C. WolfgangRobert S. HaganMichael R. YeamanThomas M. WeissXinhua ChenMelody M. H. LiVictor NizetSilvio AntoniakNigel MackmanRichard L. GalloGerard C. L. WongaDepartment of Bioengineering, University of California, Los Angeles, CA 90095bDepartment of Chemistry and Biochemistry, University of California, Los Angeles, CA 9009cCalifornia NanoSystems Institute, University of California, Los Angeles, CA 90095dDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA 90095eBiomedical Engineering, School of Engineering, Westlake University, Hangzhou, Zhejiang 310012, ChinafUniversity of North Carolina Blood Research Center, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599gDepartment of Dermatology, University of California San Diego, La Jolla, CA 92093hDivision of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215iDepartment of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA 92093jStanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Stanford University, Menlo Park, CA 94025kDivision of Molecular Medicine, Harbor-University of California Los Angeles Medical Center, Los Angeles County, Torrance, CA 90502lDivision of Infectious Diseases, Harbor-University of California Los Angeles Medical Center, Los Angeles County, Torrance, CA 90502mDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095nInstitute for Infection & Immunity, Lundquist Institute for Biomedical Innovation, Harbor-University of California Los Angeles Medical Center, Torrance, CA 90502oEnvironmental Molecular Science Division, Pacific Northwest National Laboratory, Richland, WA 99354pBiological Science Division, Pacific Northwest National Laboratory, Richland, WA 99354qDivision of Oral and Craniofacial Health Sciences, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599rDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599sMcAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599tDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599uComputational Medicine Program, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599vMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599wDivision of Pulmonary Diseases and Critical Care Medicine, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599xDepartment of Pathology and Laboratory Medicine, University of North Carolina Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
Proceedings of the National Academy of Sciences: Immunology and Inflammation, 3.02.2024
Tilføjet 3.02.2024
Proceedings of the National Academy of Sciences, Volume 121, Issue 6, February 2024.
Læs mere Tjek på PubMedImmunity, 31.01.2024
Tilføjet 31.01.2024
Publication date: Available online 30 January 2024 Source: Immunity Author(s): Naina Gour, Hwan Mee Yong, Aishwarya Magesh, Aishwarya Atakkatan, Felipe Andrade, Stephane Lajoie, Xinzhong Dong
Læs mere Tjek på PubMedLaurène Meyniel-SchicklinJérôme AmaudrutPierre MallinjoudFabrice GuillierPhilippe E. MangeotLaetitia LinesAnne Aublin-GexCaroline ScholtesClaire PunginelliStéphane JolyFlorence VasseurEvelyne ManetHenri GruffatThomas HenryFarès HalitimJean-Laurent PaparinPeter MachinRaphaël DarteilDiane SampsonIvan MikaelianLydie LaneVincent NavratilMarie-Pierre Golinelli-CohenFabiola TerziPatrice AndréVincent LotteauJacky VonderscherEric C. MeldrumBenoit de ChasseyaENYO Pharma, Lyon 69008, FrancebInventiva, Daix 21121, FrancecCentre International de Recherche en Infectiologie, University Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Lyon 69007, FrancedUniversité de Paris, INSERM U1151, CNRS UMR 8253, Institut Necker Enfants Malades, Département “Croissance et Signalisation”, Paris 75015, FranceeUniversité de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de recherche en cancérologie de Lyon, Lyon 69373, FrancefComputer and Laboratory Investigation of Proteins of Human Origin Group, Swiss Institute of Bioinformatics, Lausanne 1015, SwitzerlandgPôle Rhône-Alpes de bioinformatique, Rhône-Alpes Bioinformatics Center, Université Lyon 1, Villeurbanne 69622, FrancehEuropean Virus Bio-informatiques Center, Jena 07743, GermanyiInstitut Français de Bioinformatique, IFB-core, UMS 3601, Évry 91057, FrancejUniversité Paris-Saclay, CNRS, Institut de Chimie des Substances Naturelles, Unité Propre de Recherche 2301, Gif-sur-Yvette 91198, France
Proceedings of the National Academy of Sciences, 31.01.2024
Tilføjet 31.01.2024
Proceedings of the National Academy of Sciences, Volume 121, Issue 5, January 2024.
Læs mere Tjek på PubMedInfection, 27.01.2024
Tilføjet 27.01.2024
Abstract Purpose Human Borna disease virus (BoDV-1) encephalitis is an emerging disease in Germany. This study investigates the spectrum of human BoDV-1 infection, characterizes anti-BoDV-1-antibodies and kinetics, and compares laboratory test performances. Methods Three hundred four encephalitis cases, 308 nation-wide neuropsychiatric conditions, 127 well-defined psychiatric cases from Borna disease-endemic areas, and 20 persons with contact to BoDV-1 encephalitis patients or animals were tested for BoDV-1 infections by serology and PCR. Results BoDV-1 infections were only found in encephalitis patients with residence in, or recent travel to, virus-endemic areas. Antibodies were detected as early as 12 days after symptom onset. Serum antibody levels correlated with disease duration. Serology was ordered after 50% of the disease duration had elapsed, reflecting low awareness. BoDV-1-antibodies were of IgG1 subclass, and the epitope on BoDV-1 antigens was determined. Specificity of the indirect immunofluorescence antibody test (IFAT) and lineblot (LB) from serum and cerebrospinal fluid (CSF), as well as PCR testing from CSF, was 100%. Sensitivity, depending on first or all samples, reached 75–86% in serum and 92–94% in CSF for the IFAT, and 33–57% in serum and 18–24% in CSF for the LB. Sensitivity for PCR in CSF was 25–67%. Positive predictive values were 100% each, while negative predictive values were 99% (IFAT), 91–97% (LB), and 90% (PCR). Conclusions There is no hint that BoDV-1 causes other diseases than encephalitis in humans. Awareness has to be increased in virus-endemic areas. Tests are robust but lack sensitivity. Detection of IgG1 against specific peptides may facilitate diagnosis. Screening of healthy individuals is likely not beneficial.
Læs mere Tjek på PubMedClinical Infectious Diseases, 26.01.2024
Tilføjet 26.01.2024
Abstract Given that HIV can be transmitted through breastfeeding, historically, breastfeeding among women with HIV in the United States and other resource rich settings was actively discouraged. Formula feeding was mandated as the only feeding option primarily out of concern for breastmilk transmission of HIV, which occurred in 16-24%1-3 of cases pre-antiretroviral therapy (ART) use. In January 2023, the United States’ Department of Health and Human Services (DHHS) Perinatal Guidelines were updated to support shared decision making for infant feeding choices4. Updated data from clinical trials in low- and middle-income settings suggest that the actual rate of HIV transmission through breastmilk in the context of maternal ART or neonatal post-exposure prophylaxis (PEP) is 0.3-1%1-3. High income countries are reporting increasing numbers of people with HIV breastfeeding their infants without cases of HIV transmission to date5-10. Here we will present the reasons for fully embracing breast/chestfeeding as a viable and safe infant feeding option for HIV-exposed infants in high-income settings now, while acknowledging unanswered questions and the need to continually craft more nuanced clinical guidance.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 26.01.2024
Tilføjet 26.01.2024
Abstract Background Severe fever with thrombocytopenia syndrome (SFTS), a lethal tick-borne hemorrhagic fever, prompted our investigation into prognostic predictors and potential drug targets using plasma Olink Proteomics.Methods Employing the Olink assay, we analyzed 184 plasma proteins in 30 survivors and 8 non-survivors of SFTS. Validation was performed in a cohort of 154 SFTS patients using enzyme-linked immunosorbent assay. We utilized the Drug Gene Interaction database to identify protein-drug interactions.Results Non-survivors exhibited 110 differentially expressed proteins (DEPs) compared to survivors, with functional enrichment in the cell chemotaxis-related pathway. Thirteen DEPs, including C-C motif chemokine 20 (CCL20), calcitonin gene-related peptide alpha and Pleiotrophin, were associated with multiple organ dysfunction syndrome. CCL20 emerged as the top predictor of death, demonstrating an area under the curve of 1 (P = .0004) and 0.9033 (P < .0001) in the discovery and validation cohort, respectively. Patients with CCL20 levels exceeding 45.74 pg/mL exhibited a fatality rate of 45.65%, while no deaths occurred in those with lower CCL20 levels. Furthermore, we identified 202 FDA-approved drugs targeting 37 death-related plasma proteins.Conclusions Distinct plasma proteomic profiles characterize SFTS patients with different outcomes, with CCL20 emerging as a novel, sensitive, accurate, and specific biomarker for predicting SFTS prognosis.
Læs mere Tjek på PubMedInfection, 25.01.2024
Tilføjet 25.01.2024
Abstract Purpose Human Borna disease virus (BoDV-1) encephalitis is an emerging disease in Germany. This study investigates the spectrum of human BoDV-1 infection, characterizes anti-BoDV-1-antibodies and kinetics, and compares laboratory test performances. Methods Three hundred four encephalitis cases, 308 nation-wide neuropsychiatric conditions, 127 well-defined psychiatric cases from Borna disease-endemic areas, and 20 persons with contact to BoDV-1 encephalitis patients or animals were tested for BoDV-1 infections by serology and PCR. Results BoDV-1 infections were only found in encephalitis patients with residence in, or recent travel to, virus-endemic areas. Antibodies were detected as early as 12 days after symptom onset. Serum antibody levels correlated with disease duration. Serology was ordered after 50% of the disease duration had elapsed, reflecting low awareness. BoDV-1-antibodies were of IgG1 subclass, and the epitope on BoDV-1 antigens was determined. Specificity of the indirect immunofluorescence antibody test (IFAT) and lineblot (LB) from serum and cerebrospinal fluid (CSF), as well as PCR testing from CSF, was 100%. Sensitivity, depending on first or all samples, reached 75–86% in serum and 92–94% in CSF for the IFAT, and 33–57% in serum and 18–24% in CSF for the LB. Sensitivity for PCR in CSF was 25–67%. Positive predictive values were 100% each, while negative predictive values were 99% (IFAT), 91–97% (LB), and 90% (PCR). Conclusions There is no hint that BoDV-1 causes other diseases than encephalitis in humans. Awareness has to be increased in virus-endemic areas. Tests are robust but lack sensitivity. Detection of IgG1 against specific peptides may facilitate diagnosis. Screening of healthy individuals is likely not beneficial.
Læs mere Tjek på PubMedBMC Infectious Diseases, 25.01.2024
Tilføjet 25.01.2024
Abstract Background Oritavancin, a long-acting lipoglycopeptide approved for use in acute bacterial skin and skin structure infections, has limited data evaluating use in serious infections due to Gram-positive organisms. We aimed to assess the effectiveness and safety of oritavancin for consolidative treatment of Gram-positive bloodstream infections (BSI), including infective endocarditis (IE). Methods We conducted a retrospective cohort study evaluating adult patients admitted to University of Colorado Hospital from March 2016 to January 2022 who received ≥ 1 oritavancin dose for treatment of Gram-positive BSI. Patients were excluded if the index culture was drawn at an outside facility or were > 89 years of age. The primary outcome was a 90-day composite failure (clinical or microbiological failure) in those with 90-day follow-up. Secondary outcomes included individual components of the primary outcome, acute kidney injury (AKI), infusion-related reactions (IRR), and institutional cost avoidance. Results Overall, 72 patients were included. Mean ± SD age was 54 ± 16 years, 61% were male, and 10% had IE. Organisms most commonly causing BSI were Staphylococcus aureus (68%, 17% methicillin-resistant), followed by Streptococcus spp. (26%), and Enterococcus spp. (10%). Patients received standard-of-care antibiotics before oritavancin for a median (IQR) of 11 (5–17) days. Composite failure in the clinically evaluable population (n = 64) at 90-days occurred in 14% and was composed of clinical and microbiological failure, which occurred in 14% and 5% of patients, respectively. Three patients (4%) experienced AKI after oritavancin, and two (3%) experienced an IRR. Oritavancin utilization resulted in earlier discharge for 94% of patients corresponding to an institutional cost-avoidance of $3,055,804 (mean $44,938/patient) from 1,102 hospital days saved (mean 16 days/patient). Conclusions The use of oritavancin may be an effective sequential therapy for Gram-positive BSI to facilitate early discharge resulting in institutional cost avoidance.
Læs mere Tjek på PubMedAnise Nkenjop HappiOlusola Akinola OgunsanyaAkeemat Opeyemi AyinlaAyotunde Elijah SijuwolaFemi Mudasiru SaibuKazeem AkanoCecilia NwofokeObineche Tobias EliasOlivia Achonduh-AtijegbeRichard Olumide DaoduOluwatobi Abel AdedokunAbraham AdeyemoKehinde Ebenezer OgundanaOmolola Zaheedat LawalEdyth ParkerIguosadolo NosamiefanJohnson OkolieZahra F. ParkerMelanie D. McCauleyLeigh Anne EllerKara LombardiAbdulwasiu Bolaji TiamiyuMichael IroezinduEdward AkinwaleThierry Lamare Fouapon Assedi NjatouTsedal MebrahtuErica BroachAnastasia ZuppePetra PrinsJenny LayMihret AmareKayvon ModjarradNatalie D. CollinsSandhya VasanCynthia TuckerSharon DayeChristian Tientcha Happia African Centre of Excellence for Genomics of Infectious Diseases, Redeemer’s University, Ede, Osun State, Nigeriab Redeemer’s University, Ede, Osun, Nigeriac Alex Ekwueme Federal University Teaching Hospital, Abakaliki, Ebonyi State, Nigeriad University of Nigeria, Nsukka, Nigeriae Scripps Translational Science Institute, La Jolla, CA, USAf Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USAg Henry M. Jackson Foundation Medical Research International Ltd/Gte, Abuja, Nigeriah Emerging Infectious Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD, USAi One Health Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD, USAk Viral Diseases Program, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD, USAl Department of Immunology and Infectious Diseases, Harvard T H Chan School of Public Health, Boston, MA, USA
Emerg Microbes Infect, 23.01.2024
Tilføjet 23.01.2024
Adenrele Oludiran, Areej Malik, Andriana C. Zourou, Yonghan Wu, Steven P. Gross, Albert Siryapon, Asia Poudel, Kwincy Alleyne, Savion Adams, David S. Courson, Myriam L. Cotten, Erin B. Purcell
PLoS One Infectious Diseases, 23.01.2024
Tilføjet 23.01.2024
by Adenrele Oludiran, Areej Malik, Andriana C. Zourou, Yonghan Wu, Steven P. Gross, Albert Siryapon, Asia Poudel, Kwincy Alleyne, Savion Adams, David S. Courson, Myriam L. Cotten, Erin B. Purcell The spore-forming intestinal pathogen Clostridioides difficile causes multidrug resistant infection with a high rate of recurrence after treatment. Piscidins 1 (p1) and 3 (p3), cationic host defense peptides with micromolar cytotoxicity against C. difficile, sensitize C. difficile to clinically relevant antibiotics tested at sublethal concentrations. Both peptides bind to Cu2+ using an amino terminal copper and nickel binding motif. Here, we investigate the two peptides in the apo and holo states as antibiotic adjuvants against an epidemic strain of C. difficile. We find that the presence of the peptides leads to lower doses of metronidazole, vancomycin, and fidaxomicin to kill C. difficile. The activity of metronidazole, which targets DNA, is enhanced by a factor of 32 when combined with p3, previously shown to bind and condense DNA. Conversely, the activity of vancomycin, which acts at bacterial cell walls, is enhanced 64-fold when combined with membrane-active p1-Cu2+. As shown through microscopy monitoring the permeabilization of membranes of C. difficile cells and vesicle mimics of their membranes, the adjuvant effect of p1 and p3 in the apo and holo states is consistent with a mechanism of action where the peptides enable greater antibiotic penetration through the cell membrane to increase their bioavailability. The variations in effects obtained with the different forms of the peptides reveal that while all piscidins generally sensitize C. difficile to antibiotics, co-treatments can be optimized in accordance with the underlying mechanism of action of the peptides and antibiotics. Overall, this study highlights the potential of antimicrobial peptides as antibiotic adjuvants to increase the lethality of currently approved antibiotic dosages, reducing the risk of incomplete treatments and ensuing drug resistance.
Læs mere Tjek på PubMedGabriele Giuliano, Sara Benedetti, Margherita Sambo, Fabio Pierguidi, Mario Tumbarello
Clinical Microbiology and Infection, 20.01.2024
Tilføjet 20.01.2024
We have read with great interest the article written by Wurcel et al. [1] published in Clin Microbiol Infect. We completely agree with the necessity to design randomized clinical trials to investigate the use of long-acting glycopeptides (LGPs) such as those for the treatment of infective endocarditis, which are now allowed off-label use, in comparison with oral therapy in people who inject drugs (PWIDs). We recently managed a 35-years-old man, who was addicted to heroin intravenously and who presented at our Emergency Department for fever and dyspnoea.
Læs mere Tjek på PubMedHai‐Ping Tang, Ya‐Ping He, Jian Wang, Jian‐Min Zhan, Wen‐Bo Lian, Feng Xue, Li Wang, Yijie Li, Ailian Zhang, Fuchun Zhang, Chen Xu, Jinyao Li, Wan‐Xiang Xu
Journal of Medical Virology, 19.01.2024
Tilføjet 19.01.2024
Thomas Karl Atkins, Arnav Solanki, George Vasmatzis, James Cornette, Marc Riedel
Frontiers in Immunology, 16.01.2024
Tilføjet 16.01.2024
Bias in neural network model training datasets has been observed to decrease prediction accuracy for groups underrepresented in training data. Thus, investigating the composition of training datasets used in machine learning models with healthcare applications is vital to ensure equity. Two such machine learning models are NetMHCpan-4.1 and NetMHCIIpan-4.0, used to predict antigen binding scores to major histocompatibility complex class I and II molecules, respectively. As antigen presentation is a critical step in mounting the adaptive immune response, previous work has used these or similar predictions models in a broad array of applications, from explaining asymptomatic viral infection to cancer neoantigen prediction. However, these models have also been shown to be biased toward hydrophobic peptides, suggesting the network could also contain other sources of bias. Here, we report the composition of the networks’ training datasets are heavily biased toward European Caucasian individuals and against Asian and Pacific Islander individuals. We test the ability of NetMHCpan-4.1 and NetMHCpan-4.0 to distinguish true binders from randomly generated peptides on alleles not included in the training datasets. Unexpectedly, we fail to find evidence that the disparities in training data lead to a meaningful difference in prediction quality for alleles not present in the training data. We attempt to explain this result by mapping the HLA sequence space to determine the sequence diversity of the training dataset. Furthermore, we link the residues which have the greatest impact on NetMHCpan predictions to structural features for three alleles (HLA-A*34:01, HLA-C*04:03, HLA-DRB1*12:02).
Læs mere Tjek på PubMedBMC Infectious Diseases, 15.01.2024
Tilføjet 15.01.2024
Keith Feldman, Sarah L. Suppes, Jennifer L. Goldman
PLoS One Infectious Diseases, 12.01.2024
Tilføjet 12.01.2024
by Keith Feldman, Sarah L. Suppes, Jennifer L. Goldman Documentation of adverse drug reactions (ADRs) is a key factor in guiding future prescribing. However, incomplete documentation is common and often fails to distinguish implicated drugs as true allergies. This in turn leads to unnecessary avoidance of implicated drug classes and may result in sub-optimal prescribing. Pharmacovigilance (PV) programs utilize a systematic approach to clarify ADR documentation and are known to improve patient safety. Yet it remains unclear if PV alters prescribing. Or, if the existence of the ADR documentation itself continues to prompt avoidance of implicated drugs. To address this, our work presents a retrospective cohort study assessing if clarification of antibiotic ADRs by a hospital-wide PV team was associated with future, safe, re-prescribing at a freestanding pediatric hospital in the midwestern United States. First, we compared the likelihood of future prescribing in an antibiotic class with an active ADR, as compared to alternative drug classes, between PV-clarified and non-clarified patients. Second, we assessed differences in adverse event rates 30-days after future prescribing based on PV clarification status. For robustness, analyses were performed on patients with ADRs in four antibiotic classes: penicillin-based beta-lactams (n = 45,642), sulfonamides/trimethoprim (n = 5,329), macrolides (n = 3,959), and glycopeptides (n = 622). Results illustrate that clarification of an ADR by PV was associated with an increased odds of future prescribing in the same drug class (Odds Ratio [95%-CI]): penicillin-based beta-lactams (1.59 [1.36–1.89]), sulfonamides/trimethoprim (2.29 [0.89–4.91]), macrolides (0.77 [0.33–1.61]), and glycopeptide (1.85 [1.12–3.20]). Notably, patients clarified by PV experienced no increase in the rate of adverse events within 30-days following the prescribing of antibiotics in the same class as an active ADR. Overall, this study provides strong evidence that PV reviews safely increase the rate of re-prescribing antibiotics even in the presence of an existing implicated drug ADR.
Læs mere Tjek på PubMedVictoria R. Adams, Leonard B. Collins, Taufika Islam Williams, Jennifer Holmes, Paul Hess, Hannah M. Atkins, Grace Scheidemantle, Xiaojing Liu, Mareca Lodge, Aaron J. Johnson, Arion Kennedy
Frontiers in Immunology, 11.01.2024
Tilføjet 11.01.2024
Background & aimsActivated CD8+ T cells are elevated in Nonalcoholic steatohepatitis (NASH) and are important for driving fibrosis and inflammation. Despite this, mechanisms of CD8+ T cell activation in NASH are largely limited. Specific CD8+ T cell subsets may become activated through metabolic signals or cytokines. However, studies in NASH have not evaluated the impact of antigen presentation or the involvement of specific antigens. Therefore, we determined if activated CD8+ T cells are dependent on MHC class I expression in NASH to regulate fibrosis and inflammation. MethodsWe used H2Kb and H2Db deficient (MHC I KO), Kb transgenic mice, and myeloid cell Kb deficient mice (LysM Kb KO) to investigate how MHC class I impacts CD8+ T cell function and NASH. Flow cytometry, gene expression, and histology were used to examine hepatic inflammation and fibrosis. The hepatic class I immunopeptidome was evaluated by mass spectrometry. ResultsIn NASH, MHC class I isoform H2Kb was upregulated in myeloid cells. MHC I KO demonstrated protective effects against NASH-induced inflammation and fibrosis. Kb mice exhibited increased fibrosis in the absence of H2Db while LysM Kb KO mice showed protection against fibrosis but not inflammation. H2Kb restricted peptides identified a unique NASH peptide Ncf2 capable of CD8+ T cell activation in vitro. The Ncf2 peptide was not detected during fibrosis resolution. ConclusionThese results suggest that activated hepatic CD8+ T cells are dependent on myeloid cell MHC class I expression in diet induced NASH to promote inflammation and fibrosis. Additionally, our studies suggest a role of NADPH oxidase in the production of Ncf2 peptide generation.
Læs mere Tjek på PubMedTassembedo, Souleymane; Mwiya, Mwiya; Mennecier, Anais; Kankasa, Chipepo; Fao, Paulin; Molès, Jean Pierre; Kania, Dramane; Chunda-Liyoka, Catherine; Sakana, Leticia Delphine; D’Ottavi, Morgana; Taofiki, Ajani Ousmane; Rutagwera, David; Wilfried-Tonga, MM; Tylleskär, Thorkild; Nagot, Nicolas; Van De Perre, Philippe
AIDS, 9.01.2024
Tilføjet 9.01.2024
Objective: Our study aimed to assess the PMTCT indicators in Burkina Faso and Zambia using a patient-orientated innovative strategy based on the second visit in the Expanded Program on Immunization (EPI-2) visit at 6–8 weeks. Design: This was a cross sectional study. Methods: We assessed women attending EPI-2 at primary healthcare facilities in Burkina Faso and Zambia with their children about their exposure to PMTCT interventions. For women living with HIV (WLHIV), viral load was measured and their children were tested for HIV DNA using point of care devices. Results: Overall, 25 093 were enrolled from Burkina Faso and 8961 women from Zambia. Almost, all women attended at least one antenatal care visit. Among those aware of their HIV-positive status, 95.8 and 99.2% were on antiretroviral therapy (ART) in Burkina Faso and Zambia, respectively. Among WLHIV on ART, 75 and 79.2% achieved a viral load suppression (viral load
Læs mere Tjek på PubMedBMC Infectious Diseases, 2.01.2024
Tilføjet 2.01.2024
Abstract Background Severe pneumonia frequently causes irreversible sequelae and represents a major health burden for children under the age of 5. Matrix Metallopeptidase 9 (MMP9) is a zinc-dependent endopeptidase that is involved in various cellular processes. The correlation between MMP9 and the risk of severe childhood pneumonia remains unclear. Methods Here we assemble a case–control cohort to study the association of genetic variants in MMP9 gene with severe childhood pneumonia susceptibility in a Southern Chinese population (1034 cases and 8426 controls). Results Our results indicate that the allele G in rs3918262 SNP was significantly associated with an increased risk of severe pneumonia. Bioinformatic analyses by expression quantitative trait loci (eQTL), RegulomeDB and FORGEdb database analysis showed that rs3918262 SNP has potential regulatory effect on translational efficiency and protein level of MMP9 gene. Furthermore, MMP9 concentrations were significantly up-regulated in the bronchoalveolar lavages (BALs) of children with severe pneumonia. Conclusion In summary, our findings suggest that MMP9 is a novel predisposing gene for childhood pneumonia.
Læs mere Tjek på PubMedSalama, H. Z., Alnajjar, Y. A., Owais, T. A., Jobran, A. W. M., Safi, R., Bahar, M., Al-Ashhab, H.
BMJ Open, 28.12.2023
Tilføjet 28.12.2023
ObjectiveTo evaluate the utilisation and outcomes of endoscopic retrograde cholangiopancreatography (ERCP) procedures, success rates, incidence and risk factors for procedural-related complications in a single centre-based study. Study designRetrospective cohort study. SettingFirst advanced tertiary endoscopy centre in Palestine. ParticipantsA total of 1909 procedures on 1303 patients were included in the analysis: females were 57.9% of the cases (n=755), 1225 patients (94%) were from West Bank and Jerusalem and 78 (6%) were from Gaza Strip. All patients who underwent ERCP throughout the period from December 2017 to September 2022 were selected to participate in the study. Primary and secondary outcome measuresThe primary outcomes of interest in our analysis were success rates, procedural outcomes and post- procedural complications including pancreatitis, bleeding and others. Two multivariate logistic regression models were performed to calculate the risk of post-ERCP complications and post-ERCP pancreatitis (PEP) in patients with certain risk factors like demographic factors, procedural techniques\' variation, pancreatic duct manipulations and others. We also discussed the management of the failed procedures. ResultsThe overall complication rate was 5%, including PEP (n=43, 2.3%), infection/cholangitis (n=20, 1%), bleeding (n=9, 0.5%) and perforation (n=7, 0.4%). The mortality rate was 0.6% (n=11). Risk factors for adverse events included pancreatic duct cannulation and PEP (p
Læs mere Tjek på PubMed