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Edward J. Schenck, Maria Plataki, Craig E. Wheelock
American Journal of Respiratory and Critical Care Medicine , 15.04.2024
Tilføjet 15.04.2024
American Journal of Respiratory and Critical Care Medicine, Volume 209, Issue 8, Page 903-904, April 15, 2024.
Læs mere Tjek på PubMedOsoul Chouchane, Alex R. Schuurman, Tom D. Y. Reijnders, Hessel Peters-Sengers, Joe M. Butler, Fabrice Uhel, Marcus J. Schultz, Marc J. Bonten, Olaf L. Cremer, Carolyn S. Calfee, Michael A. Matthay, Raymond J. Langley, Narges Alipanah-Lechner, Stephen F. Kingsmore, Angela Rogers, Michel van Weeghel, Frédéric M. Vaz, Tom van der Poll
American Journal of Respiratory and Critical Care Medicine , 15.04.2024
Tilføjet 15.04.2024
American Journal of Respiratory and Critical Care Medicine, Volume 209, Issue 8, Page 973-986, April 15, 2024.
Læs mere Tjek på PubMedJasper Fuk-Woo Chan, Shuofeng Yuan, Hin Chu, Siddharth Sridhar, Kwok-Yung Yuen
Nat Rev Microbiol, 15.04.2024
Tilføjet 15.04.2024
Alessandro ManconAngelo Roberto RaccagniGloria GagliardiDavide MoscheseAlberto RizzoAndrea GiacomelliMiriam CutreraFederica SalariFiorenza BracchittaSpinello AntinoriAndrea GoriGiuliano RizzardiniAntonella CastagnaMaria Rita GismondoSilvia NozzaDavide Miletoa Laboratory of Clincal Microbiology, Virology and Bioemergencies, ASST Fatebenefratelli Sacco, Milan, Italyb Vita-Salute San Raffaele University, Milan, Italyc University of Milan, Milan, Italyd Department of Infectious Diseases, ASST Fatebenefratelli Sacco, Milan, Italye Department of Infectious Diseases, San Raffaele Hospital, Milan, Italyf CNR-SCITEC, Istituto di Scienze e Tecnologie Chimiche “Giulio Natta”, via C. Golgi 19, 20133 Milan, Italy
Emerg Microbes Infect, 15.04.2024
Tilføjet 15.04.2024
Tao WangRui LuoJing ZhangJing LanZhanhao LuHuanjie ZhaiLian-Feng LiYuan SunHua-Ji Qiua State Key Laboratory for Animal Disease Control and Prevention, National African Swine Fever Para-Reference Laboratory, National High Containment Facilities for Animal Diseases Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of Chinab College of Animal Sciences, Yangtze University, Jingzhou, People’s Republic of China
Emerg Microbes Infect, 15.04.2024
Tilføjet 15.04.2024
Yaqin BaiHui LeiWenjun SongSang-Chul ShinJiaqi WangBiying XiaoZeynep A. KoçerMin-Suk SongRobert WebsterRichard J. WebbySook-San WongMark Zanina HKU-Pasteur Research Pole, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of Chinab Guangzhou Medical University, Guangzhou, People’s Republic of Chinac State Key Laboratory of Respiratory Diseases, Guangzhou, People’s Republic of Chinad School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of Chinae Centre for Immunology & Infection, Hong Kong SAR, People's Republic of Chinaf Guangzhou Laboratory, Guangzhou International Bio Island, Guangzhou, People’s Republic of Chinag Korea Institute of Science and Technology, Seoul, Koreah Emerging Viral Diseases Laboratory, Izmir Biomedicine and Genome Center, Izmir, Türkiyei Department of Biomedicine and Health Technologies, Izmir International Biomedicine and Genome Institute, Izmir, Türkiyej Department of Microbiology, Chungbuk National University Medical School, Chungbuk, Koreak Department of Host-Microbe Interactions, St. Jude Children’s Research Hospital, Memphis, TN, USA
Emerg Microbes Infect, 15.04.2024
Tilføjet 15.04.2024
Clinical & Experimental Immunology, 15.04.2024
Tilføjet 15.04.2024
Abstract Peri-implantitis and periodontitis are common oral inflammatory diseases, which seem to exhibit critical differences in some of their molecular features. Thus, we assessed the immune cell composition of peri-implantitis and periodontitis lesions and the corresponding inflammatory profile in soft tissues and crevicular fluid. Peri-implantitis, periodontitis and control patients were recruited (n=62), and soft tissue biopsies were collected during surgery. Crevicular fluid around implant or tooth was collected. The proportions of major immune cell populations in tissues were analyzed by flow cytometry, and the inflammatory profile in tissue and crevicular fluid by a multiplex immunoassay. No significant difference was seen between peri-implantitis and periodontitis lesions in the proportions of immune cells. Peri-implantitis tissues showed an increased frequency of B cells in comparison with control tissues, along with higher levels of IL-1β, TNF-α, IL-4, and BAFF in tissue and crevicular fluid. Moreover, TNF-α, IL-17A and BAFF were higher in peri-implantitis tissues, but not in periodontitis, than in control tissues. The immune cell composition did not differ significantly between peri-implantitis and periodontitis, but an enhanced inflammatory profile was seen in peri-implantitis tissue. Peri-implantitis lesions were enriched in B cells, and displayed increased levels of IL-1β, TNF-α, IL-4, and BAFF in both tissue and crevicular fluid.
Læs mere Tjek på PubMedInfection, 15.04.2024
Tilføjet 15.04.2024
Abstract Background The global mortality rate resulting from HIV-associated cryptococcal disease is remarkably elevated, particularly in severe cases with dissemination to the lungs and central nervous system (CNS). Regrettably, there is a dearth of predictive analysis regarding long-term survival, and few studies have conducted longitudinal follow-up assessments for comparing anti-HIV and antifungal treatments. Methods A cohort of 83 patients with HIV-related disseminated cryptococcosis involving the lung and CNS was studied for 3 years to examine survival. Comparative analysis of clinical and immunological parameters was performed between deceased and surviving individuals. Subsequently, multivariate Cox regression models were utilized to validate mortality predictions at 12, 24, and 36 months. Results Observed plasma cytokine levels before treatment were significantly lower for IL-1RA (p
Læs mere Tjek på PubMedSaberian, Chantal; Lurain, Kathryn; Hill, Lindsay K.; Marshall, Vickie; Castro, Elena M. Cornejo; Labo, Nazzarena; Miley, Wendell; Moore, Kyle; Roshan, Romin; Ruggerio, Margie; Ryan, Kerry; Widell, Anaida; Ekwede, Irene; Mangusan, Ralph; Rupert, Adam; Barochia, Amisha; Whitby, Denise; Yarchoan, Robert; Ramaswami, Ramya
AIDS, 14.04.2024
Tilføjet 14.04.2024
Objective: Kaposi sarcoma is a vascular tumor that affects the pulmonary system. However, the diagnosis of airway lesions suggestive of pulmonary Kaposi sarcoma (pKS) is reliant on bronchoscopic visualization. We evaluated the role of Kaposi sarcoma herpesvirus (KSHV) viral load in bronchoalveolar lavage (BAL) as a diagnostic biomarker in patients with bronchoscopic evidence of pKS and evaluated inflammatory cytokine profiles in BAL and blood samples. Design: In this retrospective study, we evaluated KSHV viral load and cytokine profiles within BAL and blood samples in patients who underwent bronchoscopy for suspected pKS between 2016 and 2021. Methods: KSHV viral load and cytokine profiles were obtained from both the circulation and BAL samples collected at the time of bronchoscopy to evaluate compartment-specific characteristics. BAL was centrifuged and stored as cell pellets and KSHV viral load was measured using primers for the KSHV K6 gene regions. Results: We evaluated 38 BAL samples from 32 patients (30 with HIV co-infection) of whom 23 had pKS. In patients with airway lesions suggestive of pKS, there was higher KSHV viral load (median 3188 vs. 0 copies/106 cell equivalent; P = 0.0047). A BAL KSHV viral load cutoff of 526 copies/106 cells had a sensitivity of 72% and specificity of 89% in determining lesions consistent with pKS. Those with pKS also had higher IL-1β and IL-8 levels in BAL. The 3-year survival rate for pKS patients was 55%. Conclusion: KSHV viral load in BAL shows potential for aiding in pKS diagnosis. Patients with pKS also have evidence of cytokine dysregulation in BAL. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedDirajlal-Fargo, Sahera; Yu, Wendy; Jacobson, Denise L.; Mirza, Ayesha; Geffner, Mitchell E.; Jao, Jennifer; Mccomsey, Grace A.; for the Pediatric HIV/AIDS Cohort Study (PHACS)
AIDS, 14.04.2024
Tilføjet 14.04.2024
The relationships between alterations in the intestinal barrier, and bacterial translocation with the development of metabolic complications in youth with perinatally-acquired HIV (YPHIV) have not been investigated. The PHACS Adolescent Master Protocol enrolled YPHIV across 15 U.S. sites, including Puerto Rico, from 2007-2009. For this analysis, we included YPHIV with HIV viral load ≤1000 c/mL, with at least one measurement of homeostatic assessment of insulin resistance (HOMA-IR) or non-high density lipoprotein (non-HDLc) between baseline and year 3 and plasma levels of intestinal fatty-acid binding protein (I-FABP), lipopolysaccharide binding protein (LBP), and zonulin levels at baseline. We fit linear regression models using generalized estimating equations to assess the association of baseline log10 gut markers with log10 HOMA-IR and non-HDLc at all timepoints. HOMA-IR or non-HDLc was measured in 237, 189, and 170 PHIV at baseline, Yr2, and Yr3, respectively. At baseline, median age (Q1, Q3) was 12 yrs (10, 14), CD4 count was 762 cells/mm3 (574, 984); 90% had HIV RNA
Læs mere Tjek på PubMedMalaria Journal, 14.04.2024
Tilføjet 14.04.2024
Abstract Background While Plasmodium falciparum and Plasmodium vivax cause the majority of malaria cases and deaths, infection by Plasmodium malariae and other Plasmodium species also causes morbidity and mortality. Current understanding of these infections is limited in part by existing point-of-care diagnostics that fail to differentiate them and have poor sensitivity for low-density infections. Accurate diagnosis currently requires molecular assays performed in well-resourced laboratories. This report describes the development of a P. malariae diagnostic assay that uses rapid, isothermal recombinase polymerase amplification (RPA) and lateral-flow-strip detection. Methods Multiple combinations of custom RPA primers and probes were designed using publicly available P. malariae genomic sequences, and by modifying published primer sets. Based on manufacturer RPA reaction conditions (TwistDx nfo kit), an isothermal assay was optimized targeting the multicopy P. malariae 18S rRNA gene with 39 °C incubation and 30-min run time. RPA product was visualized using lateral strips (FAM-labeled, biotinylated amplicon detected by a sandwich immunoassay, visualized using gold nanoparticles). Analytical sensitivity was evaluated using 18S rRNA plasmid DNA, and clinical sensitivity determined using qPCR-confirmed samples collected from Tanzania, Ethiopia, and the Democratic Republic of the Congo. Results Using 18S rRNA plasmid DNA, the assay demonstrates a detection limit of 10 copies/µL (~ 1.7 genome equivalents) and 100% analytical specificity. Testing in field samples showed 95% clinical sensitivity and 88% specificity compared to qPCR. Total assay time was less than 40 min. Conclusion Combined with simplified DNA extraction methods, the assay has potential for future field-deployable, point-of-care use to detect P. malariae infection, which remains largely undiagnosed but a neglected cause of chronic malaria. The assay provides a rapid, simple readout on a lateral flow strip without the need for expensive laboratory equipment.
Læs mere Tjek på PubMedInfection, 14.04.2024
Tilføjet 14.04.2024
Abstract Background The global mortality rate resulting from HIV-associated cryptococcal disease is remarkably elevated, particularly in severe cases with dissemination to the lungs and central nervous system (CNS). Regrettably, there is a dearth of predictive analysis regarding long-term survival, and few studies have conducted longitudinal follow-up assessments for comparing anti-HIV and antifungal treatments. Methods A cohort of 83 patients with HIV-related disseminated cryptococcosis involving the lung and CNS was studied for 3 years to examine survival. Comparative analysis of clinical and immunological parameters was performed between deceased and surviving individuals. Subsequently, multivariate Cox regression models were utilized to validate mortality predictions at 12, 24, and 36 months. Results Observed plasma cytokine levels before treatment were significantly lower for IL-1RA (p
Læs mere Tjek på PubMedInfection, 14.04.2024
Tilføjet 14.04.2024
Abstract Background Within endemic regions in southern and eastern Germany, Borna disease virus 1 (BoDV-1) causes rare zoonotic spill-over infections in humans, leading to encephalitis with a high case-fatality risk. So far, intra-vitam diagnosis has mainly been based on RT-qPCR from cerebrospinal fluid (CSF) and serology, both being associated with diagnostic challenges. Whilst low RNA copy numbers in CSF limit the sensitivity of RT-qPCR from this material, seroconversion often occurs late during the course of the disease. Case presentation Here, we report the new case of a 40 − 50 year-old patient in whom the detection of virus-specific T cells via ELISpot corroborated the diagnosis of BoDV-1 infection. The patient showed a typical course of the disease with prodromal symptoms like fever and headaches 2.5 weeks prior to hospital admission, required mechanical ventilation from day three after hospitalisation and remained in deep coma until death ten days after admission. Results Infection was first detected by positive RT-qPCR from a CSF sample drawn four days after admission (viral load 890 copies/mL). A positive ELISpot result was obtained from peripheral blood collected on day seven, when virus-specific IgG antibodies were not detectable in serum, possibly due to previous immune adsorption for suspected autoimmune-mediated encephalitis. Conclusion This case demonstrates that BoDV-1 ELISpot serves as additional diagnostic tool even in the first week after hospitalisation of patients with BoDV-1 encephalitis.
Læs mere Tjek på PubMedInfection, 14.04.2024
Tilføjet 14.04.2024
Abstract Purpose Sepsis has a high incidence and a poor prognosis. Early recognition is important to facilitate timely initiation of adequate care. Sepsis screening tools, such as the (quick) Sequential Organ Failure Assessment ((q)SOFA) and National Early Warning Score (NEWS), could help recognize sepsis. These tools have been validated in a general immunocompetent population, while their performance in immunocompromised patients, who are particularly at risk of sepsis development, remains unknown. Methods This study is a post hoc analysis of a prospective observational study performed at the emergency department. Inclusion criteria were age ≥ 18 years with a suspected infection, while ≥ two qSOFA and/or SOFA criteria were used to classify patients as having suspected sepsis. The primary outcome was in-hospital mortality. Results 1516 patients, of which 40.5% used one or more immunosuppressives, were included. NEWS had a higher prognostic accuracy as compared to qSOFA for predicting poor outcome among immunocompromised sepsis patients. Of all tested immunosuppressives, high-dose glucocorticoid therapy was associated with a threefold increased risk of both in-hospital and 28-day mortality. Conclusion In contrast to NEWS, qSOFA underestimates the risk of adverse outcome in patients using high-dose glucocorticoids. As a clinical consequence, to adequately assess the severity of illness among immunocompromised patients, health care professionals should best use the NEWS.
Læs mere Tjek på PubMedErik Svensson, Hannah Ketelsen, Sönke Andres, Dorte Bek Folkvardsen, Doris Hillemann, Ousman Conteh, Anders Norman, Stefan Niemann, Troels Lillebaek, Martin Kuhns
Clinical Microbiology and Infection, 14.04.2024
Tilføjet 14.04.2024
We evaluated the ability of FluoroType MTBDR version 2 (FTv2; Hain Lifescience), a second-step real-time PCR assay, to simultaneously detect Mycobacterium tuberculosis complex (MTBC) DNA and mutations conferring resistance to rifampicin (RIF) and isoniazid (INH), in pulmonary and extrapulmonary samples from patients and compared them with corresponding cultures.
Læs mere Tjek på PubMedBMC Infectious Diseases, 13.04.2024
Tilføjet 13.04.2024
Abstract Background Immunosuppression is a leading cause of septic death. Therefore, it is necessary to search for biomarkers that can evaluate the immune status of patients with sepsis. We assessed the diagnostic and prognostic value of low-density neutrophils (LDNs) and myeloid-derived suppressor cells (MDSCs) subsets in the peripheral blood mononuclear cells (PBMCs) of patients with sepsis. Methods LDNs and MDSC subsets were compared among 52 inpatients with sepsis, 33 inpatients with infection, and 32 healthy controls to investigate their potential as immune indicators of sepsis. The percentages of LDNs, monocytic MDSCs (M-MDSCs), and polymorphonuclear MDSCs (PMN-MDSCs) in PBMCs were analyzed. Sequential organ failure assessment (SOFA) scores, C-reactive protein (CRP), and procalcitonin (PCT) levels were measured concurrently. Results The percentages of LDNs and MDSC subsets were significantly increased in infection and sepsis as compared to control. MDSCs performed similarly to CRP and PCT in diagnosing infection or sepsis. LDNs and MDSC subsets positively correlated with PCT and CRP levels and showed an upward trend with the number of dysfunctional organs and SOFA score. Non-survivors had elevated M-MDSCs compared with that of patients who survived sepsis within 28 days after enrollment. Conclusions MDSCs show potential as a diagnostic biomarker comparable to CRP and PCT, in infection and sepsis, even in distinguishing sepsis from infection. M-MDSCs show potential as a prognostic biomarker of sepsis and may be useful to predict 28-day hospital mortality in patients with sepsis.
Læs mere Tjek på PubMedClinical Infectious Diseases, 13.04.2024
Tilføjet 13.04.2024
Abstract Background Antiretroviral therapy (ART)-related weight gain is of particular concern in people with HIV (PWH). While weight gain was observed among PWH receiving tenofovir alafenamide (TAF), little is known about the potential reversibility after TAF discontinuation. We evaluated weight and metabolic changes 12 months after TAF discontinuation in the Swiss HIV Cohort Study.Methods We included participants who received at least six months of TAF-containing ART between January 2016 and March 2023. Using multivariable mixed-effect models, changes in weight and lipid levels were compared between individuals who continued TAF and those who switched to one of the following TAF-free regimens: TDF-based ART, dolutegravir/lamivudine (DTG/3TC), or long-acting cabotegravir/rilpivirine (CAB/RPV).Results Of 6555 participants (median age 54 years, 24.3% female, 13% Black), 5485 (83.7%) continued and 1070 (16.3%) stopped TAF. Overall, discontinuing TAF was associated with an adjusted mean weight change of -0.54 kg (95% CI -0.98 to -0.11) after 12 months. In stratified analyses, switching from TAF to TDF led to an adjusted mean weight decrease of -1.84 kg (CI -2.72 to -0.97), and to a decrease in mean total cholesterol (-0.44 mmol/L) and triglycerides (-0.38 mmol/L) after 12 months. Switching from TAF-based ART to DTG/3TC (-0.17 kg, CI -0.82 to 0.48) or long-acting CAB/RPV (-0.64 kg, CI -2.16 to 0.89) did not lead to reductions in weight.Conclusions Replacing TAF with TDF in PWH led to a decrease in body weight and an improved lipid profile within one year. Weight changes were not observed among individuals who switched to DTG/3TC or long-acting CAB/RPV.
Læs mere Tjek på PubMedCassandra Laurie, Mariam El‐Zein, Joseph E. Tota, Pierre‐Paul Tellier, François Coutlée, Ann N. Burchell, Eduardo L. Franco
Journal of Medical Virology, 13.04.2024
Tilføjet 13.04.2024
Xie, W., Xiao, J., Chen, J., Huang, H., Huang, X., He, S., Xu, L.
BMJ Open, 13.04.2024
Tilføjet 13.04.2024
IntroductionInfluenza is a major public health threat, and vaccination is the most effective prevention method. However, vaccination coverage remains suboptimal. Low health literacy regarding influenza vaccination may contribute to vaccine hesitancy. This study aims to evaluate the effect of health education interventions on influenza vaccination rates and health literacy. Methods and analysisThis cluster randomised controlled trial will enrol 3036 students in grades 4–5 from 20 primary schools in Dongguan City, China. Schools will be randomised to an intervention group receiving influenza vaccination health education or a control group receiving routine health education. The primary outcome is the influenza vaccination rate. Secondary outcomes include health literacy levels, influenza diagnosis rate, influenza-like illness incidence and vaccine protection rate. Data will be collected through questionnaires, influenza surveillance and self-reports at baseline and study conclusion. Ethics and disseminationEthical approval has been sought from the Ethics Committee of the School of Public Health, Sun Yat-sen University. Findings from the study will be made accessible to both peer-reviewed journals and key stakeholders. Trial registration numberNCT06048406.
Læs mere Tjek på PubMedAnna Sophia Feix, Anja Joachim
Trends in Parasitology, 13.04.2024
Tilføjet 13.04.2024
Cystoisospora suis, an obligate intracellular protozoan parasite of the order Coccidia, causes porcine cystoisosporosis predominantly in suckling piglets, with significant economic losses in the pig-producing industry worldwide. It has a direct life cycle with sporulated oocysts as transmissible stages and, despite its monoxenic development, is a close relative of Toxoplasma gondii and Neospora caninum. Unlike any other member of the Coccidia, however, C. suis can be cultivated in vitro in all developmental phases, allowing for detailed studies on the morphology, development, transcriptomic, and proteomic makeup of asexual, presexual, and, specifically, sexual stages (gametes) which are frequently only poorly accessible in this order due to their short life span and low number.
Læs mere Tjek på PubMedIman Satti, Julia L Marshall, Stephanie A Harris, Rachel Wittenberg, Rachel Tanner, Raquel Lopez Ramon, Morven Wilkie, Fernando Ramos Lopez, Michael Riste, Daniel Wright, Marco Polo Peralta Alvarez, Nicola Williams, Hazel Morrison, Elena Stylianou, Pedro Folegatti, Daniel Jenkin, Samantha Vermaak, Linnea Rask, Ingrid Cabrera Puig, Rebecca Powell Doherty, Alison Lawrie, Paul Moss, Timothy Hinks, Henry Bettinson, Helen McShane
Lancet Infectious Diseases, 13.04.2024
Tilføjet 13.04.2024
This first-in-human aerosol BCG controlled human infection model was sufficiently well tolerated. Further work will evaluate the utility of this model in assessing vaccine efficacy and identifying potential correlates of protection.
Læs mere Tjek på PubMedKaren O’Leary
Nature, 13.04.2024
Tilføjet 13.04.2024
Infection, 13.04.2024
Tilføjet 13.04.2024
Abstract Background Within endemic regions in southern and eastern Germany, Borna disease virus 1 (BoDV-1) causes rare zoonotic spill-over infections in humans, leading to encephalitis with a high case-fatality risk. So far, intra-vitam diagnosis has mainly been based on RT-qPCR from cerebrospinal fluid (CSF) and serology, both being associated with diagnostic challenges. Whilst low RNA copy numbers in CSF limit the sensitivity of RT-qPCR from this material, seroconversion often occurs late during the course of the disease. Case presentation Here, we report the new case of a 40 − 50 year-old patient in whom the detection of virus-specific T cells via ELISpot corroborated the diagnosis of BoDV-1 infection. The patient showed a typical course of the disease with prodromal symptoms like fever and headaches 2.5 weeks prior to hospital admission, required mechanical ventilation from day three after hospitalisation and remained in deep coma until death ten days after admission. Results Infection was first detected by positive RT-qPCR from a CSF sample drawn four days after admission (viral load 890 copies/mL). A positive ELISpot result was obtained from peripheral blood collected on day seven, when virus-specific IgG antibodies were not detectable in serum, possibly due to previous immune adsorption for suspected autoimmune-mediated encephalitis. Conclusion This case demonstrates that BoDV-1 ELISpot serves as additional diagnostic tool even in the first week after hospitalisation of patients with BoDV-1 encephalitis.
Læs mere Tjek på PubMedInfection, 13.04.2024
Tilføjet 13.04.2024
Abstract Purpose Sepsis has a high incidence and a poor prognosis. Early recognition is important to facilitate timely initiation of adequate care. Sepsis screening tools, such as the (quick) Sequential Organ Failure Assessment ((q)SOFA) and National Early Warning Score (NEWS), could help recognize sepsis. These tools have been validated in a general immunocompetent population, while their performance in immunocompromised patients, who are particularly at risk of sepsis development, remains unknown. Methods This study is a post hoc analysis of a prospective observational study performed at the emergency department. Inclusion criteria were age ≥ 18 years with a suspected infection, while ≥ two qSOFA and/or SOFA criteria were used to classify patients as having suspected sepsis. The primary outcome was in-hospital mortality. Results 1516 patients, of which 40.5% used one or more immunosuppressives, were included. NEWS had a higher prognostic accuracy as compared to qSOFA for predicting poor outcome among immunocompromised sepsis patients. Of all tested immunosuppressives, high-dose glucocorticoid therapy was associated with a threefold increased risk of both in-hospital and 28-day mortality. Conclusion In contrast to NEWS, qSOFA underestimates the risk of adverse outcome in patients using high-dose glucocorticoids. As a clinical consequence, to adequately assess the severity of illness among immunocompromised patients, health care professionals should best use the NEWS.
Læs mere Tjek på PubMedInfection, 13.04.2024
Tilføjet 13.04.2024
Abstract Purpose To evaluate clinical outcomes associated with sotrovimab use during Omicron BA.2 and BA.5 predominance. Methods Electronic databases were searched for observational studies published in peer-reviewed journals, preprint articles and conference abstracts from January 1, 2022 to February 27, 2023. Results The 14 studies identified were heterogeneous in terms of study design, population, endpoints and definitions. They included > 1.7 million high-risk patients with COVID-19, of whom approximately 41,000 received sotrovimab (range n = 20–5979 during BA.2 and n = 76–1383 during BA.5 predominance). Four studies compared the effectiveness of sotrovimab with untreated or no monoclonal antibody treatment controls, two compared sotrovimab with other treatments, and three single-arm studies compared outcomes during BA.2 and/or BA.5 versus BA.1. Five studies descriptively reported rates of clinical outcomes in patients treated with sotrovimab. Rates of COVID-19-related hospitalization or mortality (0.95–4.0% during BA.2; 0.5–2.0% during BA.5) and all-cause mortality (1.7–2.0% during BA.2; 3.4% during combined BA.2 and BA.5 periods) among sotrovimab-treated patients were consistently low. During BA.2, a lower risk of all-cause hospitalization or mortality was reported across studies with sotrovimab versus untreated cohorts. Compared with other treatments, sotrovimab was associated with a lower (molnupiravir) or similar (nirmatrelvir/ritonavir) risk of COVID-19-related hospitalization or mortality during BA.2 and BA.5. There was no significant difference in outcomes between the BA.1, BA.2 and BA.5 periods. Conclusions This systematic literature review suggests continued effectiveness of sotrovimab in preventing severe clinical outcomes during BA.2 and BA.5 predominance, both against active/untreated comparators and compared with BA.1 predominance.
Læs mere Tjek på PubMedInfection, 13.04.2024
Tilføjet 13.04.2024
Abstract Purpose The prevalence of obesity is an escalating concern in modern populations, predominantly attributed to the widespread adoption of sedentary lifestyles observed globally. Extensive research has established a significant association between obesity and Helicobacter pylori (H. pylori). Nonetheless, a comprehensive assessment of the global prevalence of H. pylori among individuals with obesity remains undetermined. Methods A systematic search strategy was applied to PubMed, Scopus, and Web of Science. The resulting records were screened using the Rayyan online tool for the management of systematic reviews. Freeman–Tukey double arcsine transformation was used. Subgroup analyses (continent, regional classifications, developmental status, religion, global hemisphere, income, access to international waters, and H. pylori eradication) and multivariate meta-regression (latitude, longitude, male-to-all ratio, mean age, and body mass index) were done to estimate the effects of the moderators. Risk of bias assessment was done using JBI checklist for prevalence studies. Results A total of 472,511 individuals with obesity from 208 studies were included. The global estimation of H. pylori prevalence among individuals with obesity was 32.3% (95% CI 26.9%, 38.0%). South America had the highest prevalence. Based on the different classifications of countries, resource-rich, low-/middle-income, developing, and Islamic countries had the highest prevalence. Lower pooled prevalence was observed in the studies with adequate sample sizes (n ≥ 270). Conclusion The findings have the potential to influence future health policies for preventing and treating H. pylori infection. However, there is variability among the included studies, indicating the need for more population-based research.
Læs mere Tjek på PubMedBreanne MeffordKatie L. WallaceJ. Chris DonaldsonBrittany D. Bissell TurpinParijat SenAric D. SchadlerLucas J. LiuMelissa L. Thompson Bastin1Department of Pharmacy Services, University of Kentucky HealthCare, Lexington, Kentucky, USA2Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, Kentucky, USA3Division of Pulmonary, Critical Care and Sleep Medicine, University of Kentucky, Lexington, Kentucky, USA4University of Kentucky Children’s Hospital, Lexington, Kentucky, USA5Department of Computer Science, University of Kentucky, Lexington, Kentucky, USA, Ryan K. Shields
Antimicrobial Agents And Chemotherapy, 13.04.2024
Tilføjet 13.04.2024
Yi Xin Liew, Aloysius Yew Leng Ho, Gee Chuan Wong, Shimin Jasmine Chung, Thuan Tong Tan, Ban Hock Tan
International Journal of Infectious Diseases, 13.04.2024
Tilføjet 13.04.2024
In Haematology, prophylaxis for Pneumocystis jirovecii pneumonia (PCP) is recommended for patients undergoing hematopoietic stem cell transplantation (HSCT) and in selected categories of intensive chemotherapy for hematological malignancies (HM) [1]. Trimethoprim–sulfamethoxazole (TMP-SMX) is the recommended first-line agent, but its use is not straightforward, as it can be associated with myelosuppression and elevation of potassium and creatinine [2]. Furthermore, many patients have a sulfa allergy, and some are G6PD (glucose-6-phosphate dehydrogenase) deficient [3].
Læs mere Tjek på PubMedGemma Lladós, Marta Massanella, Roger Paredes, Lourdes Mateu
Clinical Microbiology and Infection, 13.04.2024
Tilføjet 13.04.2024
BMC Infectious Diseases, 13.04.2024
Tilføjet 13.04.2024
Abstract Background Non-tuberculous mycobacteria (NTM) are environmental organisms that are increasingly contributing to human infections. Mycobacterium immunogenum, a variant of NTM discovered in 2001, is a rapidly growing mycobacterium that exhibits multidrug resistance. Reports of infections caused by this organism, particularly tenosynovitis in the musculoskeletal system, are limited. Case presentation A 71-year-old female with vesicular pemphigus, undergoing immunosuppressive therapy, presented with a progressively enlarging tumour on the dorsum of her right hand, along with erythematous papules that extended across her right forearm. The specimens of skin tissues and blood cultures revealed the presence of M. immunogenum. Magnetic resonance imaging evaluation led to the diagnosis of pyogenic extensor tenosynovitis. A multidrug regimen, comprising amikacin and clarithromycin, was initiated, followed by synovectomy. The patient underwent a course of 180 days of antimicrobial therapy and demonstrated no signs of disease recurrence one year after treatment completion. Conclusion Early diagnosis and surgical intervention are crucial to prevent the adverse prognostic implications of pyogenic extensor tenosynovitis caused by M. immunogenum. Effective management requires precise microbial identification and susceptibility testing, necessitating collaborative engagement with microbiological laboratories.
Læs mere Tjek på PubMedBMC Infectious Diseases, 13.04.2024
Tilføjet 13.04.2024
Abstract Background Tuberculosis (TB) and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) co-morbidity continues to be a serious worldwide health issue, particularly in Sub-Saharan Africa. Studies on the quality of life (QOL) of TB/HIV co-infected patients guide stakeholders on the delivery of patient-centred healthcare. This study evaluated QOL of TB/HIV co-infected individuals and its contributing factors. Methods We conducted a cross-sectional study among TB/HIV co-infected patients, receiving treatment at clinics in the Northern Region of Ghana. Simple random sampling technique was used to select 213 patients from 32 clinics. We gathered information on patients’ QOL using the World Health Organization QOL-HIV BREF assessment tool. At a 5% level of significance, multiple logistic regression analyses were carried out to find correlates of QOL among the patients. Results The mean age of the patients was (38.99 ± 14.00) years with most, 33.3% (71/213) aged 30–39 years. Males constituted 54.9% (117/213). About 30.0% (64/213) of the patients reported a good QOL. Being employed (aOR = 5.23, 95% CI: 1.87 – 14.60), and adhering to treatment (aOR = 6.36, 95% CI: 1.51 – 26.65) were significantly associated with a good QOL. Being depressed (aOR = 0.02, 95% CI: 0.03 – 0.29), stigmatized (aOR = 0.31, 95% CI : 0.11 – 0.84), and not exercising (aOR = 0.28, 95% CI: 0.12 – 0.67) were negatively associated with a good QOL. Conclusion Less than one-third of TB/HIV co-infected patients in the region have good QOL. To guarantee good QOL, modifiable predictors such as patients’ physical activity and medication adherence should be targeted by the National AIDS and TB Control Programs.
Læs mere Tjek på PubMedBMC Infectious Diseases, 13.04.2024
Tilføjet 13.04.2024
Abstract Background This study aims to explore the potential of utilizing the expression levels of cannabinoid receptor 2 (CB2), μ-opioid receptor (MOR), MCP-1, IL-17, IFN-γ, and osteopontin as predictors for the severity of SARS-CoV-2 infection. The overarching goal is to delineate the pathogenic mechanisms associated with SARS-CoV-2. Methods Using quantitative Real-time PCR, we analyzed the gene expression levels of CB2 and MOR in nasopharynx specimens obtained from patients diagnosed with SARS-CoV-2 infection, with 46 individuals classified as having severe symptoms and 46 as non-severe. Additionally, we measured the circulating levels of MCP-1, IL-17, IFN-γ, and osteopontin using an ELISA assay. We examined the predictive capabilities of these variables and explored their correlations across all patient groups. Results Our results demonstrated a significant increase in MOR gene expression in the epithelium of patients with severe infection. The expression of CB2 receptor was also elevated in both male and female patients with severe symptoms. Furthermore, we observed concurrent rises in MCP-1, IL-17, IFN-γ, and osteopontin levels in patients, which were linked to disease severity. CB2, MOR, MCP-1, IL-17, IFN-γ, and osteopontin showed strong predictive abilities in distinguishing between patients with varying degrees of SARS-CoV-2 severity. Moreover, we identified a significant correlation between CB2 expression and the levels of MOR, MCP-1, osteopontin, and IFN-γ. Conclusions These results underline the interconnected nature of molecular mediators in a sequential manner, suggesting that their overexpression may play a role in the development of SARS-CoV-2 infections. Graphical Abstract
Læs mere Tjek på PubMedBMC Infectious Diseases, 13.04.2024
Tilføjet 13.04.2024
Abstract Background Cryptococcal osteomyelitis is a rare and potentially serious condition, typically encountered in individuals with compromised immune systems. This case underscores the unusual occurrence of disseminated Cryptococcosis in an immunocompetent person, involving multiple bones and lungs, with Cryptococcus neoformans identified as the causative agent. Case presentation An Indonesian man, previously in good health, presented with a chief complaint of successive multiple bone pain lasting for more one month, without any prior history of trauma. Additionally, he reported a recent onset of fever. On physical examination, tenderness was observed in the left lateral chest wall and right iliac crest. Laboratory findings indicated mildly elevated inflammatory markers. A computed tomography (CT) scan of the chest revealed an ovoid solid nodule in the right lower lung and multifocal osteolytic lesions in the sternum, ribs, and humeral head. A magnetic resonance imaging (MRI) study of the sacrum showed multiple lesions in the bilateral iliac bone and the lower L4 vertebral body. Confirmation of Cryptococcal osteomyelitis involved a fine-needle biopsy and culture, identifying Cryptococcus neoformans in the aspirate. The patient responded positively to targeted antifungal treatments, leading to a gradual improvement in his condition. Conclusions This case emphasizes the need to consider Cryptococcus neoformans osteomyelitis in immunocompetent patients with bone pain. A definitive diagnosis involves a fine-needle biopsy for pathology and culture, and prompt initiation of appropriate antifungal treatment has proven effective in preventing mortality.
Læs mere Tjek på PubMedNikolaj Pagh Kristensen, Edoardo Dionisio, Amalie Kai Bentzen, Tripti Tamhane, Janine Sophie Kemming, Grigorii Nos, Lasse Frank Voss, Ulla Kring Hansen, Georg Michael Lauer, Sine Reker Hadrup
Science Advances, 12.04.2024
Tilføjet 12.04.2024
Estie Hon-Kiu ShunJianwen SituJames Yiu-Hung TsoiShusheng WuJianpiao CaiKelvin Hon-Yin LoNicholas Foo-Siong ChewZhiyu LiRosana Wing-Shan PoonJade Lee-Lee TengVincent Chi-Chung ChengKwok-Yung YuenSiddharth Sridhara Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of Chinab Centre for Virology, Vaccinology and Therapeutics, Health@InnoHK, The University of Hong Kong, Hong Kong, People’s Republic of Chinac Faculty of Dentistry, The University of Hong Kong, Hong Kong, People’s Republic of Chinad State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, People’s Republic of Chinae Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
Emerg Microbes Infect, 12.04.2024
Tilføjet 12.04.2024
Malaria Journal, 12.04.2024
Tilføjet 12.04.2024
Abstract Background The emergence of resistance to artemisinin-based combination therapy necessitates the search for new, more potent antiplasmodial compounds, including herbal remedies. The whole extract of Maytenus senegalensis has been scientifically investigated for potential biological activities both in vitro and in vivo, demonstrating strong antimalarial activity. However, there is a lack of data on the electrocardiographic effects of M. senegalensis in humans, which is a crucial aspect in the investigation of malaria treatment. Assessing the electrocardiographic effects of M. senegalensis is essential, as many anti-malarial drugs can inadvertently prolong the QT interval on electrocardiograms. Therefore, the study\'s objective was to evaluate the electrocardiographic effects of M. senegalensis in healthy adult volunteers. Methods This study is a secondary analysis of an open-label single-arm dose escalation. Twelve healthy eligible Tanzanian males, aged 18 to 45, were enrolled in four study dose groups. A single 12-lead electrocardiogram (ECG) was performed at baseline and on days 3, 7, 14, 28, and 56. Results No QTcF adverse events occurred with any drug dose. Only one volunteer who received the highest dose (800 mg) of M. senegalensis experienced a moderate transient change (△QTcF > 30 ms; specifically, the value was 37 ms) from baseline on day 28. There was no difference in maximum QTcF and maximum △QTcF between volunteers in all four study dose groups. Conclusions A four-day regimen of 800 mg every 8 h of M. senegalensis did not impact the electrocardiographic parameters in healthy volunteers. This study suggests that M. senegalensis could be a valuable addition to malaria treatment, providing a safer alternative and potentially aiding in the battle against artemisinin-resistant malaria. The results of this study support both the traditional use and the modern therapeutic potential of M. senegalensis. They also set the stage for future research involving larger and more diverse populations to explore the safety profile of M. senegalensis in different demographic groups. This is especially important considering the potential use of M. senegalensis as a therapeutic agent and its widespread utilization as traditional medicine. Trial registration ClinicalTrials.gov, NCT04944966. Registered 30 June 2021-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04944966?term=kamaka&draw=2&rank=1
Læs mere Tjek på PubMedStephen J. BillingtonEva U. WieckowskiMahfuzur R. SarkerDawn BueschelJ. Glenn SongerBruce A. McClane
Infection and Immunity, 12.04.2024
Tilføjet 12.04.2024
Journal of Infectious Diseases, 12.04.2024
Tilføjet 12.04.2024
Abstract Background Respiratory syncytial virus (RSV) causes substantial respiratory disease. Bivalent RSV prefusion F (RSVpreF) vaccine is licensed in ≥60-year-olds. RSVpreF was well-tolerated and immunogenic in a phase 1/2 study. We evaluated antibody persistence after initial vaccination and safety and immunogenicity after revaccination from this study.Methods Healthy adults were randomized to receive both initial vaccination and revaccination 12 months later with either placebo or RSVpreF 240 µg (±Al(OH)3). RSV-A and RSV-B geometric mean neutralizing titers (GMTs) were measured through 12 months after both vaccinations. Tolerability/safety was assessed.Results There were 263 participants revaccinated (18−49-years-old, n=134; 65−85-years-old, n=129). Among 18−49-year-olds and 65−85-year-olds, respectively, geometric mean fold rises (GMFRs) for both RSV subgroups (RSV-A; RSV-B) 1 month after initial RSVpreF vaccination were 13.3−20.4 and 8.9−15.5 compared with levels before initial vaccination; corresponding GMFRs 12 months after initial vaccination were 4.1−5.0 and 2.6−4.1. GMFRs 1 month after revaccination compared with levels before revaccination were 1.4−2.3 and 1.4−2.2 for 18−49-year-olds and 65−85-year-olds, respectively. Peak GMTs after revaccination were lower than those after initial vaccination. GMTs 12 months after initial vaccination and revaccination were similar, with GMFRs ranging from 0.7−1.6. No safety signals occurred.Conclusions RSVpreF revaccination was immunogenic and well-tolerated among adults. NCT03529773
Læs mere Tjek på PubMedRemigius Gröning, Jonatan Walde, Clas Ahlm, Mattias NE Forsell, Johan Normark, Johan Rasmuson
International Journal of Infectious Diseases, 12.04.2024
Tilføjet 12.04.2024
The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a major public health concern since the start of the 2019 pandemic. Although current vaccines protect the general public, individuals with severe immunodeficiencies often exhibit a poor vaccine response and a higher risk of severe and/or persistent disease [1,2]. There are no treatment recommendations for persistent infection in immunocompromised individuals. Attempts with repeated antiviral mono or combination therapy has been described [3].
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