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Shalu Verma-Kumar, David Abraham, Nandini Dendukuri, Jacob Varghese Cheeran, Raman Sukumar, Kithiganahalli Narayanaswamy Balaji
PLoS One Infectious Diseases, 14.11.2023
Tilføjet 14.11.2023
by Shalu Verma-Kumar, David Abraham, Nandini Dendukuri, Jacob Varghese Cheeran, Raman Sukumar, Kithiganahalli Narayanaswamy Balaji
Læs mere Tjek på PubMedEuri Seo, Eun Seok Choi, Jung Hwa Kim, Hyery Kim, Kyung-Nam Koh, Ho Joon Im, Jina Lee
PLoS One Infectious Diseases, 14.11.2023
Tilføjet 14.11.2023
by Euri Seo, Eun Seok Choi, Jung Hwa Kim, Hyery Kim, Kyung-Nam Koh, Ho Joon Im, Jina Lee
Læs mere Tjek på PubMedJisu Kim, In-Whi Hwang, Jeong-Hui Park, Youngdeok Kim, Jung-Min Lee
PLoS One Infectious Diseases, 14.11.2023
Tilføjet 14.11.2023
by Jisu Kim, In-Whi Hwang, Jeong-Hui Park, Youngdeok Kim, Jung-Min Lee The current study is to examine the disparities in physical activity (PA), sedentary behavior (SB), and stress levels in Korean adolescents concerning changes in their perception of family economic status (ES) during COVID-19. Among a total of 6144 Korean adolescents aged 12 to 18, the participants were categorized into two groups based on their responses regarding changes in their family ES due to COVID-19: Declined ES (n = 3072) and Non-changed ES (n = 3072), with matching in terms of age, gender, and BMI. All variables were assessed using the 16th year (2020) of the Korean Youth Risk Behavior Survey. Statistical analyses were conducted using the SPSS 26.0 version, employing independent t-tests to examine anthropometrics’ differences and multinominal logistic regression to predict the impact of perception of family ES on PA, SB, and stress while comparing the two groups. The significance level was set at α = 0.05. Adolescents in the Declined ES group were 1.2 times more likely to engage in MVPA for less than 420 mins/wk (OR = 1.16, p = 0.039), 1.7 times more likely to meet recommended muscular strength activities (i.e., ≥ 3 days/wk) (OR = 1.70, p < 0.001), 37% less likely to not meet recommended recreational sitting time (i.e., ≥ 840 mins/wk) (OR = 0.63, p < 0.01), and were 2.1 times more likely to experience very severe stress level than the Non-changed ES group (p < 0.001). These results shed light on the importance of promoting mental health care in adolescents, regardless of PA levels, for their well-being during potential future pandemics. Understanding the impact of perceived ES changes on health behaviors can inform targeted interventions and support strategies to improve the mental health outcomes of adolescents during challenging times.
Læs mere Tjek på PubMedAdriana Castillo-Villanueva, Horacio Reyes-Vivas, Jesús Oria-Hernández
PLoS One Infectious Diseases, 14.11.2023
Tilføjet 14.11.2023
by Adriana Castillo-Villanueva, Horacio Reyes-Vivas, Jesús Oria-Hernández An empirical observation suggests that Giardia lamblia proteins have larger cysteine content than their counterparts in other organisms. As this parasite lacks conventional antioxidant stress systems, it is generally accepted that high cysteine content helps G. lamblia cope with oxygen toxicity, a strategy apparently shared by other organisms. Here, we question whether the high cysteine content in some organisms is genuine or just a simple assumption based on singular observations. To this end, we analyzed the cysteine content in 78 proteomes of organisms spanning the three domains of life. The results indicate that the cysteine content in eukaryota is approximately double that in archaea and bacteria, with G. lamblia among the highest. Atypical cysteine contents were found in a few organisms correlating with specific environmental conditions, supporting the evolutionary amino acid-level selection of amino acid composition.
Læs mere Tjek på PubMedEmily A. Simpson, Helen J. Stacey, Ross J. Langley, Joshua D. Jones
PLoS One Infectious Diseases, 14.11.2023
Tilføjet 14.11.2023
by Emily A. Simpson, Helen J. Stacey, Ross J. Langley, Joshua D. Jones Bacterial resistance or tolerance to antibiotics is costly to patients and healthcare providers. With the impact of antibiotic resistance forecast to grow, alternative antimicrobial approaches are needed to help treat patients with antibiotic refractory infections and reduce reliance upon existing antibiotics. There is renewed interest in bacteriophage (phage) therapy as a promising antimicrobial strategy. We therefore performed the first multi-specialty survey about phage therapy and the first such survey among clinicians in the United Kingdom. An anonymous 10-question survey of clinicians from medical and surgical specialties in two Scottish Health Boards was performed. The 90 respondents spanned 26 specialties and were predominantly consultants (73.3%). The respondents were concerned about antibiotic resistance in their clinical practice; 83 respondents estimated having seen 711 patients in the last 12 months whose infections were refractory to antibiotics (delaying or preventing resolution). Over half (58.8%) of the respondents had previously heard of phage therapy. Staphylococci, Pseudomonas and E. coli were identified as the highest cross-specialty priorities for the development of phage therapy. Together, 77 respondents estimated seeing 300 patients in the last 12 months for whom phage therapy may have been appropriate (an average of 3.9 patients per clinician). Most respondents (71.1%, n = 90) were already willing to consider using phage therapy in appropriate cases. Additional comments from the respondents affirmed the potential utility of phage therapy and highlighted a need for more information. The results of this survey demonstrate substantial demand for and willingness to use phage therapy in appropriate cases, both from individual clinicians and across specialties. Demand from a wide range of specialties illustrates the broad clinical utility of phage therapy and potential scope of impact. Widening access to phage therapy could deliver substantial clinical and financial benefits for patients and health authorities alike.
Læs mere Tjek på PubMedMalaria Journal, 14.11.2023
Tilføjet 14.11.2023
Abstract Background The overlap in the epidemiology of malaria and helminths has been identified as a potential area to exploit for the development of an integrated control strategy that may help to achieve elimination of malaria and helminths. A randomized, controlled, observer-blind trial was conducted to assess the feasibility and safety of combining mass drug administration (MDA) for schistosomiasis and soil transmitted helminths (STH) with seasonal malaria chemoprevention (SMC) among children living in Senegal. Methods Female and male children aged 1–14 years were randomized 1:1:1, to receive Vitamin A and Zinc on Day 0, followed by SMC drugs (sulfadoxine-pyrimethamine and amodiaquine) on Days 1–3 (control group); or praziquantel and Vitamin A on Day 0, followed by SMC drugs on Days 1–3 (treatment group 1); or albendazole and praziquantel on Day 0, followed by SMC drugs on Days 1–3 (treatment group 2). Safety assessment was performed by collecting adverse events from all children for six subsequent days following administration of the study drugs. Pre- and post-intervention, blood samples were collected for determination of haemoglobin concentration, malaria microscopy, and PCR assays. Stool samples were analyzed using Kato-Katz, Merthiolate-iodine-formalin and PCR methods. Urine filtration, PCR and circulating cathodic antigen tests were also performed. Results From 9 to 22 June 2022, 627 children aged 1–14 years were randomized into the three groups described above. Mild, transient vomiting was observed in 12.6% (26/206) of children in treatment group 2, in 10.6% (22/207) in group 1, and in 4.2% (9/214) in the control group (p = 0.005). Pre-intervention, the geometric mean value of Plasmodium falciparum parasite density was highest among children who received albendazole, praziquantel with SMC drugs. Post-intervention, the parasite density was highest among children who received SMC drugs only. Children who received praziquantel and SMC drugs had a lower risk of developing severe anaemia than their counterparts who received SMC drugs alone (OR = 0.81, 95% CI 0.13–5.00, p = 0.63). Conclusions Integration of MDA for helminths with SMC drugs was safe and feasible among Senegalese children. These findings support further evaluation of the integrated control model. Trial registration: The study is registered at Clinical Trial.gov NCT05354258.
Læs mere Tjek på PubMedInfection, 14.11.2023
Tilføjet 14.11.2023
Abstract Purpose Given reduced immunity levels for seasonally occurring respiratory infections and the experience of an unusually early, severe wave of RSV infections during 2021, a preexisting clinician-led reporting system (CLRS) was updated to prospectively monitor the anticipated high burden of respiratory infections (ARI) in German pediatric hospitals during fall/winter 2022–2023. Methods From September 13, 2022 through March 31, 2023, children hospitalized with ARI as a primary diagnosis were monitored via a national CLRS established by the German Society for Pediatric Infectious Diseases (DGPI). Once a week, the CLRS collected overall number of new hospital admissions, ARI-related admissions according to pathogen (SARS-CoV-2, RSV, influenza, and other), plus number of patients admitted to ICU with ARI as a primary diagnosis. Results With a high participation among children\'s hospitals across Germany (22.8%), 76 centers submitted 1,053 survey reports. ARI-related hospital admissions showed a steep rise starting in late September 2022 and reached their highpoint in early December 2022 (50.1% of all admissions). In parallel, the average number of newly admitted patients (aNA) with RSV (3.6) peaked, as did those with influenza (2.1) one week later. The average highpoint of ARI patients on ICU (aICU) (2.9) was reached shortly thereafter. Again, RSV (1.6) und influenza (1.2) were predominant pathogens. Conclusion In fall/winter 2022–2023, German hospitals reported a sharp increase in patients with ARIs. While RSV and influenza represented the greatest proportion of ARI, SARS-CoV-2 played a less significant role. Systematic, dynamic collection of ARI data is critical for assessing real burdens on the health care system.
Læs mere Tjek på PubMedSalvatore Rotundo, Francesco Bono, Maria Mazzitelli, Vincenzo Scaglione, Angelo Giuseppe Lamberti, Aida Giancotti, Luigi Tucci, Chiara Costa, Maria Teresa Tassone, Helen Linda Morrone, Enrico Maria Trecarichi, Carlo Torti
International Journal of Infectious Diseases, 14.11.2023
Tilføjet 14.11.2023
Bartonella spp. includes fastidious Gram-negative bacilli infecting blood-sucking arthropod vectors and mammalian hosts [1]. The pathological manifestations of Bartonella spp. infections are widely heterogeneous, ranging from asymptomatic bacteremia to vascular proliferative disorders such as bacillary peliosis and cutaneous bacillary angiomatosis (cBA) [1-3], which are caused by B. henselae, B. bacilliformis or B. quintana [1, 2, 4]. Cat bites and scratches and owning a cat bearing fleas are the most common risk factors identified in cBA due to B.
Læs mere Tjek på PubMedThinley Dorji, Kristy Horan, Norelle L Sherry, Ee Laine Tay, Maria Globan, Linda Viberg, Katherine Bond, Justin T Denholm, Benjamin P Howden, Patiyan Andersson
International Journal of Infectious Diseases, 14.11.2023
Tilføjet 14.11.2023
Globally, millions of people are infected with Mycobacterium tuberculosis, with most cases concentrated in developing countries. The burden of tuberculosis (TB) is low in most industrialised countries, and clusters of cases mostly arise from index cases who acquired the disease overseas. In Australia, TB is mostly diagnosed among migrants from high TB burden countries, healthcare workers, and among communities of First Nations Peoples [1]. The high frequency among migrant populations is primarily due to reactivation of latent TB.
Læs mere Tjek på PubMedBMC Infectious Diseases, 14.11.2023
Tilføjet 14.11.2023
Abstract Background Pro–b-type natriuretic peptide (Pro-BNP) is an inflammatory marker that indicates cardiac damage and inflammation. The elevation of this marker in COVID-19 patients can be used as a predictive factor in the prognosis of these patients. Method Our cross-sectional study investigated the evaluation of cardiac diagnostic test findings based on pro-BNP levels in pregnant COVID-19 patients in Sayyad Shirazi Hospital, Gorgan, Iran, in 2020–2022. A hundred and ten pregnant patients diagnosed with COVID-19 infection were evaluated for cardiac diagnostic tests (electrocardiogram (ECG) and echocardiography (Echo)) and pro-BNP levels. Data were analyzed using SPSS 25 software. Chi-square and Student\'s t-test will be used to test and compare the relationship between variables and compare them. A P-value less than 0.05 is considered statistically significant. The chi-square test was used to compare the ratio of qualitative variables among the groups if the presuppositions of chi-square distribution were established. Otherwise, Fisher\'s exact test was used. Result The mean age of participants were 31.06 ± 5.533 years and 49.1% of patients had pro-BNP levels above the cut-off value for predicting an adverse outcome of COVID-19. The mean ± standard deviation of pro-BNP levels in the low group was 46.125 ± 17.523 pg/mL and in the high group was 878.814 ± 1038.060 pg/mL. This study revealed that patients with higher pro-BNP plasma levels had a significant relation between, myocardial infarction (MI), pericardial effusion (PE), urgent Caesarean section (C/S), and mortality. In addition, no significant relation between gravid, trimester, vaccination, arrhythmia, heart block, and valves diseases with high pro-BNP levels was found. Conclusion The current research showed that pro-BNP levels can be used as a diagnostic and valuable prognostic tool in pregnant women to diagnose cardiac complications by using ECG and Echo.
Læs mere Tjek på PubMedBMC Infectious Diseases, 14.11.2023
Tilføjet 14.11.2023
Abstract Background Dermatophytes are the most common causative pathogens of mycoses worldwide and usually cause superficial infections. However, they can enter deep into the dermis lead to invasive dermatophytosis such as deeper dermal dermatophytosis on rare occasions. Erythroderma is a severe dermatological manifestation of various diseases resulting in generalized skin redness, but erythroderma due to fungi infections is barely reported. In this article, we reported the first case of erythroderma combined with deeper dermal dermatophytosis due to Trichophyton rubrum (T. rubrum) in a patient with myasthenia gravis. Case presentation A 48-year-old man was hospitalized because of erythema with scaling and nodules covering his body for a month. The patient had a history of myasthenia gravis controlled by regularly taking prednisolone for > 10 years and accompanied by onychomycosis and tinea pedis lasting > 8 years. Based on histopathological examinations, fungal cultures, and DNA sequencing results, the patient was finally diagnosed with dermatophyte-induced erythroderma combined with deeper dermal dermatophytosis caused by T. rubrum. After 2 weeks of antifungal treatment, the patient had recovered well. Conclusions This case report shows that immunosuppressed patients with long histories of superficial mycoses tend to have a higher risk of developing invasive dermatophytic infections or disseminated fungal infections. Dermatologists should be alert to this condition and promptly treat the superficial dermatophytosis.
Læs mere Tjek på PubMedBMC Infectious Diseases, 14.11.2023
Tilføjet 14.11.2023
Abstract Background Leptospirosis is an infectious disease caused by pathogenic Leptospira spp., which could result in severe illnesses. Indirect contact with these pathogens is more common. Individuals could contract this disease through contact with contaminated water or during floods. In this case, we present the details of a 40-year-old male pig farmer who suffered from severe pulmonary hemorrhagic leptospirosis and multiple organ failure. The diagnosis of leptospirosis was confirmed through metagenomics next-generation sequencing (mNGS) while the patient received extracorporeal membrane oxygenation (ECMO) support, and antibiotic treatment was adjusted accordingly. The patient underwent comprehensive treatment and rehabilitation in the intensive care unit. Conclusion This case illustrates the importance of early diagnosis and treatment of leptospirosis. While obtaining the epidemiological history, second-generation metagenomics sequencing was utilized to confirm the etiology. The prompt initiation of ECMO therapy provided a crucial window of opportunity for addressing the underlying cause. This case report offers valuable insights for diagnosing patients with similar symptoms.
Læs mere Tjek på PubMedBMC Infectious Diseases, 14.11.2023
Tilføjet 14.11.2023
Abstract Background Chronic kidney disease (CKD) was reported to be a risk factor of cardiac implantable electronic device (CIED) infection. The application of bundled skin antiseptic preparation before CIED implantation decreased the risk of CIED infection, even in patients undergoing complex procedures. However, the effect of bundled skin antiseptic preparation to prevent CIED infection in patients with CKD was not tested. Methods Between July 2012 and December 2019, 1668 patients receiving CIEDs comprised this retrospective cohort study and were categorized into two groups by the diagnosis of CKD: group with CKD (n = 750, 45%) and group without CKD (n = 918, 55%). The primary outcome was clinical CIED infection, including major and minor infection, and the secondary outcomes were cardiovascular mortality and all-cause mortality. Propensity score matching (PSM) was applied to reduce selection bias between the study groups. Results During a 4-year follow-up period, 30 patients (1.8%) had a CIED infection. After PSM, the incidence of CIED infection was similar between the patients with CKD and without CKD (1.0% vs. 1.8%). The incidences of cardiovascular mortality and all-cause mortality were higher in patients with CKD compared to patients without CKD (6.5% vs. 3.0%, P = 0.009; 22.8% vs. 11.8%, P
Læs mere Tjek på PubMedFleur M. Ferguson
Nature, 13.11.2023
Tilføjet 13.11.2023
Nature, 13.11.2023
Tilføjet 13.11.2023
Maryam Shahmanesh, Natsayi Chimbindi, Frances M. Cowan
Nature, 13.11.2023
Tilføjet 13.11.2023
Karen O’Leary
Nature, 13.11.2023
Tilføjet 13.11.2023
Emmanuel Montassier, Georgios D. Kitsios, Josiah E. Radder, Quentin Le Bastard, Brendan J. Kelly, Ariane Panzer, Susan V. Lynch, Carolyn S. Calfee, Robert P. Dickson, Antoine Roquilly
Nature, 13.11.2023
Tilføjet 13.11.2023
Journal of Infectious Diseases, 13.11.2023
Tilføjet 13.11.2023
AbstractAdaptive platform trials can be more efficient than classic trials for developing new treatments. Moving from culture-based to simpler- or faster-to-measure biomarkers as efficacy surrogates may enhance this advantage. We performed a systematic review of treatment efficacy biomarkers in adults with tuberculosis.Platform trials can span different development phases. We grouped biomarkers as: α, bacterial load estimates used in phase 2a trials; β, early and end-of treatment endpoints, phase 2b-c trials; γ, post-treatment or trial-level estimates, phase 2c-3 trials. We considered as analysis unit (biomarker entry) each combination of biomarker, predicted outcome, and their respective measurement times or intervals. Performance metrics included: sensitivity, specificity, area under the receiver-operator curve (AUC), and correlation measures, ,and classified as poor, promising, or good.Eighty-six studies included 22864 participants. From 1356 biomarker entries, 318 were reported with the performance metrics of interest, with 103 promising and 41 good predictors. Group results: α, mycobacterial RNA and Lipoarabinomannan in sputum, and host metabolites in urine; β, mycobacterial RNA and host transcriptomic or cytokine signatures for early treatment response; γ, host transcriptomics for recurrence.A combination of biomarkers from different categories could help designing more efficient platform trials. Efforts to develop efficacy surrogates should be better coordinated.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 13.11.2023
Tilføjet 13.11.2023
AbstractBackgroundAnnual influenza vaccination is recommended for older adults but repeated vaccination with standard-dose influenza vaccine has been linked to reduced immunogenicity and effectiveness, especially against A(H3N2) viruses.MethodsCommunity-dwelling Hong Kong adults aged 65-82 years were randomly allocated to receive 2017/18 standard-dose quadrivalent, MF59-adjuvanted trivalent, high-dose trivalent, and recombinant-HA quadrivalent vaccination. Antibody response to unchanged A(H3N2) vaccine antigen was compared among participants with and without self-reported prior year (2016/17) standard-dose vaccination.ResultsMean fold rise (MFR) in antibody titers from Day 0 to Day 30 by hemagglutination inhibition and virus microneutralization assays were lower among 2017/18 standard-dose and enhanced vaccine recipients with (range, 1.7-3.0) vs. without (range, 4.3-14.3) prior 2016/17 vaccination. MFR was significantly reduced by about one half to four fifths for previously vaccinated recipients of standard-dose and all three enhanced vaccines (β range, 0.21-0.48). Among prior-year vaccinated older adults, enhanced vaccines induced higher 1.43 to 2.39-fold geometric mean titers and 1.28 to 1.74-fold MFR vs. standard-dose vaccine by microneutralization assay.ConclusionsIn the context of unchanged A(H3N2) vaccine strain, prior-year vaccination was associated with reduced antibody response among both standard-dose and enhanced influenza vaccine recipients. Enhanced vaccines improved antibody response among older adults with prior-year standard-dose vaccination.
Læs mere Tjek på PubMedIsabella L. Platz, Malte M. Tetens, Ram Dessau, Svend Ellermann-Eriksen, Nanna S. Andersen, Veronika Vorobieva Solholm Jensen, Christian Østergaard, Jacob Bodilsen, Kirstine Kobberøe Søgaard, Jette Bangsborg, Alex Christian Yde Nielsen, Jens Kjølseth Møller, Anne-Mette Lebech, Lars Haukali Omland, Niels Obel
Clinical Microbiology and Infection, 13.11.2023
Tilføjet 13.11.2023
We compared characteristics and outcomes of individuals who in the cerebrospinal fluid (CSF) were positive for herpes simplex virus (HSV) or varicella-zoster virus (VZV)-intrathecal antibody index test ((AI)-positive) vs individuals who were PCR-positive for HSV type 1 (HSV1), type 2 (HSV2), and for varicella-zoster virus (VZV).
Læs mere Tjek på PubMedClinical & Experimental Immunology, 13.11.2023
Tilføjet 13.11.2023
AbstractCD8 T cells recognize infected and cancerous cells via their T cell receptor (TCR), which binds peptide-MHC complexes on the target cell. The affinity of the interaction between the TCR and peptide-MHC contributes to the antigen sensitivity, or functional avidity, of the CD8 T cell. In response to peptide-MHC stimulation, the TCR-CD3 complex and CD8 co-receptor are downmodulated. We quantified CD3 and CD8 downmodulation following stimulation of human CD8 T cells with CMV, EBV, and HIV peptides spanning eight MHC restrictions, observing a strong correlation between the levels of CD3 and CD8 downmodulation and functional avidity, regardless of peptide viral origin. In TCR-transduced T cells targeting a tumor-associated antigen, changes in TCR-peptide affinity were sufficient to modify CD3 and CD8 downmodulation. Correlation analysis and generalized linear modelling indicated that CD3 downmodulation was the stronger correlate of avidity. CD3 downmodulation, simply measured using flow cytometry, can be used to identify high-avidity CD8 T cells in a clinical context.
Læs mere Tjek på PubMedClinical & Experimental Immunology, 13.11.2023
Tilføjet 13.11.2023
AbstractMicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression and different immune-related pathways. There is great interest to identify miRNAs involved in immune cell development and function in order to elucidate the biological mechanisms underlying immune system, its regulation, and disease. In this study we aimed to investigate the association of circulating miRNAs with blood cell compositions and blood-based immune markers. Circulating levels of 2083 miRNAs were measured by RNA-sequencing in plasma samples of 1999 participants from the population-based Rotterdam Study collected between 2002 and 2005. Full blood count measurements were performed for absolute granulocyte, platelet, lymphocyte, monocyte, white and red blood cell counts. Multivariate analyses were performed to test the association of miRNAs with blood cell compositions and immune markers. We evaluated the overlap between predicted target genes of candidate miRNAs associated with immune markers and genes determining the blood immune response markers. First, principal component regression analysis showed that plasma levels of circulating miRNAs were significantly associated with red blood cell, granulocyte, and lymphocyte counts. Second, cross-sectional analysis identified 210 miRNAs significantly associated (P
Læs mere Tjek på PubMedAna Flávia Vieira Trindade, Whesley Tanor Silva, Vanessa Pereira Lima, Vanessa Amaral Mendonça, Ana Cristina Rodrigues Lacerda, Matheus Ribeiro Ávila, Lucas Fróis Fernandes de Oliveira, Igor Lucas Geraldo Izalino de Almeida, Keity Lamary Souza Silva, Luciano Fonseca Lemos de Oliveira, Liliany Mara Silva Carvalho, Paulo Henrique da Cruz Ferreira, Sanny Cristina Castro de Faria, Mauro Felippe Felix Mediano, Pedro Henrique Scheidt Figueiredo, Henrique Silveira Costa
Tropical Medicine & International Health, 13.11.2023
Tilføjet 13.11.2023
Infection, 13.11.2023
Tilføjet 13.11.2023
Infection, 13.11.2023
Tilføjet 13.11.2023
Abstract Purpose Sternal osteomyelitis is a major complication of cardiac operations performed through median sternotomy. The surgical treatment, which involves the debridement and removal of whole infected and necrotic tissue is the standard of care, although it is sometimes unachievable. This may occur, for instance, when the infectious-inflammatory process invades the anterior mediastinum and tenaciously incorporates one or more of vital anatomical structures. Methods and results An inoperable case of postoperative sternal osteomyelitis that involved the right ventricle and the right coronary artery, and that was successfully treated using a nonsurgical multidisciplinary approach, is reported here. Conclusion For highly selected patients with sternal osteomyelitis for whom surgery is a too risky option, an approach including the contribution of various specialists might be a viable way out.
Læs mere Tjek på PubMedFederica Bellerba, Nils Bardeck, Michael Boehm, Oriana D'Ecclesiis, Sara Raimondi, Elisa Tomezzoli, Mafalda Silva Miranda, Inês Martins Alves, Daniela Alves, Ana Abecasis, Valeria Gabellone, Elisa Gabrielli, Giulia Vaglio, Elham Shamsara, Nico Pfeifer, Chiara Mommo, Francesca Incardona, Rolf Kaiser, Sara Gandini
International Journal of Infectious Diseases, 12.11.2023
Tilføjet 12.11.2023
As part of the global reaction to stop the spread of SARS-CoV-2 during the early months of the COVID-19 pandemic, primary and secondary schools were closed to on-site learning in many countries. This decision was based on data extrapolated from influenza transmission models, which suggested that closing schools could help reduce the spread of infections[1]. However, the effectiveness of this measure for SARS-CoV-2 was unclear. Several studies about the impact of school openings found conflicting results on community transmission, with some suggesting substantial increases in positivity rates[2], and others suggesting a small impact[3], [4] or no effect after adjusting for community incidence[5]–[7].
Læs mere Tjek på PubMedBMC Infectious Diseases, 12.11.2023
Tilføjet 12.11.2023
Abstract Background Spontaneous bacterial peritonitis (SBP) is a common complication in patients with cirrhosis. The diagnosis of SBP is still mostly based on ascites cultures and absolute ascites polymorphonuclear (PMN) cell count, which restricts the widely application in clinical settings. This study aimed to identify reliable and easy-to-use biomarkers for both diagnosis and prognosis of cirrhotic patients with SBP. Methods We conducted a retrospective study including 413 cirrhotic patients from March 2013 to July 2022 in the First Affiliated Hospital of Guangxi Medical University. Patients’ clinical characteristics and laboratory indices were collected and analyzed. Two machine learning methods (Xgboost and LASSO algorithms) and a logistic regression analysis were adopted to screen and validate the indices associated with the risk of SBP. A predictive model was constructed and validated using the estimated area under curve (AUC). The indices related to the survival of cirrhotic patients were also analyzed. Results A total of 413 cirrhotic patients were enrolled in the study, of whom 329 were decompensated and 84 were compensated. 52 patients complicated and patients with SBP had a poorer Child–Pugh score (P
Læs mere Tjek på PubMedMalaria Journal, 11.11.2023
Tilføjet 11.11.2023
Abstract Background Malaria affects millions of Cameroonian children under 5 years of age living in the North and Far North regions. These regions bear the greatest burden, particularly for children under 5 years of age. To reduce the burden of disease in these regions, Cameroon adopted the Seasonal Malaria Chemoprevention (SMC) in 2016 and has implemented it each year since its adoption. However, no previous studies have systematically assessed the effects of this intervention in Cameroon. It is important to understand its effect and whether its implementation could be improved. This study aimed to assess the effect of SMC in Cameroon during the period 2016–2021 on malaria morbidity in children under 5 years of age using routine data. Methods Data on malaria cases were extracted from the Cameroon Health Monitoring Information System (HMIS) from January 1, 2011, to December 31, 2021. Health facilities report these data monthly on a single platform, the District Health Information System version 2 (DHIS2). Thus, a controlled interrupted time-series model in a Bayesian framework was used to evaluate the effects of the SMC on malaria morbidity. Results SMC implementation was associated with a reduction in the incidence of uncomplicated malaria cases during the high-transmission periods from 2016 to 2021. Regarding the incidence of severe malaria during the high-transmission period, a reduction was found over the period 2016–2019. The highest reduction was registered during the second year of implementation in 2017:15% (95% Credible Interval, 10–19) of uncomplicated malaria cases and 51% (47–54) of confirmed severe malaria cases. Conclusion The addition of SMC to the malaria intervention package in Cameroon decreased the incidence of uncomplicated and severe malaria among children under 5 years of age. Based on these findings, this study supports the wide implementation of SMC to reduce the malaria burden in Cameroon as well as the use of routine malaria data to monitor the efficiency of the strategy in a timely manner.
Læs mere Tjek på PubMedAsra Fazlollahi; Mahdi Zahmatyar; Ali Shamekh; Alireza Motamedi; Fatemeh Seyedi; Homa Seyedmirzaei; Seyed Ehsan Mousavi; Seyed Aria Nejadghaderi; Mark J. M. Sullman; Ali‐Asghar Kolahi; Shahnam Arshi; Saeid Safiri;
Reviews in Medical Virology, 11.11.2023
Tilføjet 11.11.2023
A number of different neurological complications have been reported following vaccination against the coronavirus disease 2019 (COVID‐19). Electroencephalogram (EEG) is one of the modalities used to evaluate the neurological complications of diseases. The aim of the present study was to identify the EEG changes in participants vaccinated against COVID‐19. PubMed, Scopus, Web of Science, medRxiv, and Google Scholar were searched up to 1 September 2022, with terms related to COVID‐19 vaccines, EEG, neurological signs/symptoms, or neurological disorders. All case reports and case series were included if the participants had received at least one dose of a COVID‐19 vaccine and a post vaccination EEG report was also reported. We used the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for case reports and case series to appraise the methodological quality of the included studies. Thirty‐one studies were included, which were comprised of 24 case reports and seven case series and a total of 36 participants. Generalised slowing and non‐convulsive focal status epilepticus were the most common EEG findings post‐COVID‐19 vaccination. The most frequent symptoms were headache, fatigue, generalised weakness, and vomiting. In addition, the most common signs were encephalopathy, post‐ictal phases, and confusion. Encephalitis, acute disseminated encephalomyelitis, and post‐vaccinal encephalopathy were the most commonly diagnosed adverse events. Furthermore, most of the imaging studies appeared normal. The EEG reports mainly showed background slowing and epileptiform discharges, encephalitis, encephalopathies, and demyelinating disorders. Future studies with larger samples and more vaccine types may help to further unravel the potential neurological effects of COVID‐19 vaccinations on recipients.
Læs mere Tjek på PubMedAdane Adugna;
Reviews in Medical Virology, 11.11.2023
Tilføjet 11.11.2023
Hepatitis B virus (HBV)‐associated liver cancer is the third most prevalent cancer‐related cause of death worldwide. Different studies have been done on the histomolecular analysis of HBV induced‐liver cancer including epigenetics which are dynamic molecular mechanisms to control gene expression without altering the host deoxyribonucleic acid, genomics characterise the integration of the viral genome with host genome, proteomics characterise how gene modifies and results overexpression of proteins, glycoproteomics discover different glyco‐biomarker candidates and show glycosylation in malignant hepatocytes, metabolomics characterise how HBV impairs a variety of metabolic functions during hepatocyte immortalisation, exosomes characterise immortalised liver cells in terms of their differentiation and proliferation, and autophagy plays a role in the development of hepatocarcinogenesis linked to HBV infection.
Læs mere Tjek på PubMedBruno Azevedo Randi; Hermes Ryoiti Higashino; Vinícius Ponzio da Silva; Erick Menezes Xavier; Vanderson Rocha; Silvia Figueiredo Costa;
Reviews in Medical Virology, 11.11.2023
Tilføjet 11.11.2023
Patients who undergo hematopoietic stem‐cell transplantation (HSCT) are more susceptible to developing severe forms of COVID‐19 with an increased risk of mortality. The aim of this study was to analyze, by performing a systematic review and meta‐analysis, all studies that evaluated COVID‐19 in HSCT adult recipients and present clinical characteristics and outcomes. Studies were eligible for inclusion if they: (I) described the clinical characteristics of COVID‐19 in adult (aged 18 years old or above) HSCT recipients; (II) described outcomes of COVID‐19 in this population, mainly lethality; (III) were full‐text articles. We searched MedLine, Embase, SCOPUS, LILACS and Web of Science for full‐text studies that evaluated COVID‐19 in adult HSCT patients until 26 Apr 2023. Two independent reviewers screened the articles and extracted the data. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Studies Reporting Prevalence Data was used to assess quality of the included studies. Meta‐analysis was performed and the pooled prevalence of severe/critical disease and of death with a 95% CI was calculated with the random‐effects model. Sixteen studies were included; seven (43.7%) were multicenter. Most of the studies were from Europe (37.5%). All of them had a low risk of bias using the JBI Checklist. A total of 1186 patients were included. Allogeneic HSCT patients were the majority in most studies, with a total of 861 patients (72.5%). The symptomatic rate was 79.4%. The pooled prevalence of severe/critical COVID‐19 was 24.0% (95% CI 0.13–0.36; = 94%; = 334/990). The pooled prevalence of death for the entire population was 17% (95% CI 0.13–0.22; = 76%; = 221/1117), 17% (95% CI 0.12–0.23; = 67%; = 152/822) for allogeneic‐HSCT and 14% (95% CI 0.08–0.22; = 65%; = 48/293) for autologous‐HSCT. In conclusion, frequently the infection of SARS‐CoV‐2 in HSCT was symptomatic and lethality is higher than in general population. Thus, it is essential to focus on the implementation of measures to mitigate the risk of SARS‐CoV‐2 infection in this population, as well as to carefully assess HSCT recipients who develop COVID‐19.
Læs mere Tjek på PubMedNicholas I. Nii‐Trebi; Thomas S. Mughogho; Anisa Abdulai; Francis Tetteh; Priscilla M. Ofosu; Mary‐Magdalene Osei; Akua K. Yalley;
Reviews in Medical Virology, 11.11.2023
Tilføjet 11.11.2023
Infectious diseases continue to be the leading cause of morbidity and mortality, and a formidable obstacle to the development and well‐being of people worldwide. Viruses account for more than half of infectious disease outbreaks that have plagued the world. The past century (1918/19–2019/20) has witnessed some of the worst viral disease outbreaks the world has recorded, with overwhelming impact especially in low‐ and middle‐income countries (LMIC). The frequency of viral disease outbreak appears to be increasing. Generally, although infectious diseases have afflicted the world for centuries and humankind has had opportunities to examine the nature of their emergence and mode of spread, almost every new outbreak poses a formidable challenge to humankind, beating the existing pandemic preparedness systems, if any, and causing significant losses. These underscore inadequacy in our understanding of the dynamics and preparedness against viral disease outbreaks that lead to epidemics and pandemics. Despite these challenges, the past 100 years of increasing frequencies of viral disease outbreaks have engendered significant improvements in response to epidemics and pandemics, and offered lessons to inform preparedness. Hence, the increasing frequency of emergence of viral outbreaks and the challenges these outbreaks pose to humankind, call for the continued search for effective ways to tackle viral disease outbreaks in real time. Through a PRISMA‐based approach, this systematic review examines the outbreak of viral diseases in retrospect to decipher the outbreak patterns, losses inflicted on humanity and highlights lessons these offer for meaningful preparation against future viral disease outbreaks and pandemics.
Læs mere Tjek på PubMedKiruthiga Mone; Jay Reddy;
Reviews in Medical Virology, 11.11.2023
Tilføjet 11.11.2023
Myocarditis can result from various infectious and non‐infectious causes that can lead to dilated cardiomyopathy (DCM) and heart failure. Among the infectious causes, viruses are commonly suspected. But the challenge is our inability to demonstrate infectious viral particles during clinical presentations, partly because by that point, the viruses would have damaged the tissues and be cleared by the immune system. Therefore, viral signatures such as viral nucleic acids and virus‐reactive antibodies may be the only readouts pointing to viruses as potential primary triggers of DCM. Thus, it becomes hard to explain persistent inflammatory infiltrates that might occur in individuals affected with chronic myocarditis/DCM manifesting myocardial dysfunctions. In these circumstances, autoimmunity is suspected, and antibodies to various autoantigens have been demonstrated, suggesting that immune therapies to suppress the autoimmune responses may be necessary. From this perspective, we endeavoured to determine whether or not the known viral causes are associated with development of autoimmune responses to cardiac antigens that include both cardiotropic and non‐cardiotropic viruses. If so, what their nature and significance are in developing chronic myocarditis resulting from viruses as primary triggers.
Læs mere Tjek på PubMedChang‐tai Zhu; Jian‐Yun Yin; Xiao‐hua Chen; Ming Liu; Shi‐gui Yang;
Reviews in Medical Virology, 11.11.2023
Tilføjet 11.11.2023
This study aimed to clarify the beneficial effect and the clinical application value of Paxlovid in the treatment of coronavirus disease‐19 (COVID‐19) through a systematic review. Databases including PubMed, Cochrane Library, Chinese Clinical Trial Registry, and were systematically searched for interventional or observational studies on the efficacy and safety of Paxlovid in the treatment of SARS‐COV‐2. The relative and absolute effect sizes for the outcomes were calculated based on the data reported in the original intervention literature. The external applicability of the evidence was analysed in terms of clinical application scenarios, patient willingness, and cost utility. One interventional and three observational studies were conducted. Four studies published in 2022, had participation sample sizes ranging 1780–109,254. Based on the randomised controlled trial data, the risk of all‐cause mortality, all‐cause death, and hospitalisation was significantly reduced in the Paxlovid group. Serious adverse events were reduced during the study. Based on observational studies, Paxlovid can significantly reduce the risk of death and hospitalisation in older patients with COVID‐19 (moderate certainty) and improve in‐hospital disease progression, composite disease progression, and viral load (low certainty). Paxlovid did not improve the outcomes of death and hospitalisation (low certainty) in patients aged
Læs mere Tjek på PubMedMaría Belén Colazo Salbetti; Gabriel Amilcar Boggio; Laura Moreno; María Pilar Adamo;
Reviews in Medical Virology, 11.11.2023
Tilføjet 11.11.2023
Human bocaviruses were first described between 2005 and 2010, identified in respiratory and enteric tract samples of children. Screening studies have shown worldwide distribution. Based on phylogenetic analysis, they were classified into four genotypes (HBoV1‐4). From a clinical perspective, human bocavirus 1 (HBoV1) is considered the most relevant, since it can cause upper and lower acute respiratory tract infection, mainly in infants, including common cold, bronchiolitis, and pneumonia, as well as wheezing in susceptible patients. However, the specific processes leading to structural, biochemical, and functional changes resulting in the different clinical presentations have not been elucidated yet. This review surveys the interactions between the virus and target cells that can potentially explain disease‐causing mechanisms. It also summarises the clinical phenotype of cases, stressing the role of HBoV1 as an aetiological agent of lower acute respiratory infection in infants, together with laboratory tests for detection and diagnosis. By exploring the current knowledge on the epidemiology of HBoV1, insights into the complex scenario of paediatric respiratory infections are presented, as well as the potential effects that changes in the circulation can have on the dynamics of respiratory agents, spotlighting the benefits of comprehensively increase insights into incidence, interrelationships with co‐circulating agents and potential control of HBoV1.
Læs mere Tjek på PubMedGeorge M. Bwire; Belinda J. Njiro; Harieth P. Ndumwa; Castory G. Munishi; Bonaventura C. Mpondo; Mathew Mganga; Emmanuel Mang'ombe; Muhammad Bakari; Raphael Z. Sangeda; Christopher R. Sudfeld; Japthet Killewo;
Reviews in Medical Virology, 11.11.2023
Tilføjet 11.11.2023
Differentiated service delivery (DSD) models, such as adherence clubs (ACs), are client‐centred approaches where clinically stable people living with HIV (PLHIV) meet to receive various services, including psychosocial support, brief symptoms screening, and refills of antiretroviral medications, among others. We conducted a review to assess the impact of DSD models, including ACs, on sustaining retention in care (RC) and achieving viral suppression (VS) among PLHIV in sub‐Saharan Africa. The review protocol was registered in PROSPERO (CRD42023418988). We searched the literature from PubMed, Scopus, Web of Science, Embase and Google Scholar from their inception through May 2023. Eligible randomised controlled trials of adherence clubs were reviewed to assess impact on retention and viral suppression. Random effect models were used to estimate the risk ratios (RR) and 95% confidence intervals (CI). The literature search yielded a total of 1596 records of which 16 randomised clinical trials were determined to be eligible. The trials were conducted in diverse populations among adults and children with a total of 13,886 participants. The RR between any DSD models and standard of care (SoC) was 1.09 (95% CI: 1.08–1.11, : 0%, :
Læs mere Tjek på PubMedShivani Malvankar; Anjali Singh; Y. S. Ravi Kumar; Swetangini Sahu; Megha Shah; Yamini Murghai; Mahendra Seervi; Rupesh K. Srivastava; Bhupendra Verma;
Reviews in Medical Virology, 11.11.2023
Tilføjet 11.11.2023
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV2) emerged in December 2019, causing a range of respiratory infections from mild to severe. This resulted in the ongoing global COVID‐19 pandemic, which has had a significant impact on public health. The World Health Organization declared COVID‐19 as a global pandemic in March 2020. Viruses are intracellular pathogens that rely on the host\'s machinery to establish a successful infection. They exploit the gene expression machinery of host cells to facilitate their own replication. Gaining a better understanding of gene expression modulation in SARS‐CoV2 is crucial for designing and developing effective antiviral strategies. Efforts are currently underway to understand the molecular‐level interaction between the host and the pathogen. In this review, we describe how SARS‐CoV2 infection modulates gene expression by interfering with cellular processes, including transcription, post‐transcription, translation, post‐translation, epigenetic modifications as well as processing and degradation pathways. Additionally, we emphasise the therapeutic implications of these findings in the development of new therapies to treat SARS‐CoV2 infection.
Læs mere Tjek på PubMedRaphael Udeh; Alberto Utrero‐Rico; Xenia Dolja‐Gore; Masoud Rahmati; Mark McEVoy; Tony Kenna;
Reviews in Medical Virology, 11.11.2023
Tilføjet 11.11.2023
There\'s critical need for risk predictors in long COVID. This meta‐analysis evaluates the evidence for an association between plasma lactate dehydrogenase (LDH) and long COVID and explores the contribution of LDH to symptoms persistent across the distinct post‐acute sequelae of COVID‐19 (PASC) domains. PubMed, EMBASE, Web of Science, and Google Scholar were searched for articles published up to 20 March 2023 for studies that reported data on LDH levels in COVID‐19 survivors with and without PASC. Random‐effect meta‐analysis was employed to estimate the standardized mean difference (SMD) with corresponding 95% confidence interval of each outcome. There were a total of 8289 study participants (3338 PASC vs. 4951 controls) from 46 studies. Our meta‐analysis compared to the controls showed a significant association between LDH elevation and Resp‐PASC [SMD = 1.07, 95%CI = 0.72, 1.41, = 0.01] but not Cardio‐PASC [SMD = 1.79, 95%CI = −0.02, 3.61, = 0.05], Neuro‐PASC [SMD = 0.19, 95%CI = −0.24, 0.61, = 0.40], and Gastrointestinal‐PASC [SMD = 0.45, 95%CI = −1.08, 1.98, = 0.56]. This meta‐analysis suggests elevated LDH can be used for predicting Resp‐PASC, but not Cardio‐PASC, Neuro‐PASC or gastrointestinal‐PASC. Thus, elevated plasma LDH following COVID infection may be considered as a disease biomarker.
Læs mere Tjek på PubMedMarta Calado; David Pires; Carolina Conceição; Quirina Santos‐Costa; Elsa Anes; José Miguel Azevedo‐Pereira;
Reviews in Medical Virology, 11.11.2023
Tilføjet 11.11.2023
Despite the success of combined antiretroviral therapy in controlling viral load and reducing the risk of human immunodeficiency virus (HIV) transmission, an estimated 1.5 million new infections occurred worldwide in 2021. These new infections are mainly the result of sexual intercourse and thus involve cells present on the genital mucosa, such as dendritic cells (DCs), macrophages (Mø) and CD4+ T lymphocytes. Understanding the mechanisms by which HIV interacts with these cells and how HIV exploits these interactions to establish infection in a new human host is critical to the development of strategies to prevent and control HIV transmission. In this review, we explore how HIV has evolved to manipulate some of the physiological roles of these cells, thereby gaining access to strategic cellular niches that are critical for the spread and pathogenesis of HIV infection. The interaction of HIV with DCs, Mø and CD4+ T lymphocytes, and the role of the intercellular transfer of viral particles through the establishment of the infectious or virological synapses, but also through membrane protrusions such as filopodia and tunnelling nanotubes (TNTs), and cell fusion or cell engulfment processes are presented and discussed.
Læs mere Tjek på PubMedGeorgina. R. HurleJulii BrainardKevin. M. TylerNorwich Medical School, University of East Anglia, Norwich, UK
Virulence, 11.11.2023
Tilføjet 11.11.2023
Benjamin KazaHector C. Aguilara Department of Microbiology, College of Agriculture and Life Sciences, Cornell University, Ithaca, NY, USAb Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University
Virulence, 11.11.2023
Tilføjet 11.11.2023
Lóser, Meghan K.; Horowitz, Jennifer K.; England, Peter; Esteitie, Rania; Kaatz, Scott; McLaughlin, Elizabeth; Munroe, Elizabeth; Heath, Megan; Posa, Pat; Flanders, Scott A.; Prescott, Hallie C.
Critical Care Explorations, 11.11.2023
Tilføjet 11.11.2023
OBJECTIVES: To identify opportunities for improving hospital-based sepsis care and to inform an ongoing statewide quality improvement initiative in Michigan. DESIGN: Surveys on hospital sepsis processes, including a self-assessment of practices using a 3-point Likert scale, were administered to 51 hospitals participating in the Michigan Hospital Medicine Safety Consortium, a Collaborative Quality Initiative sponsored by Blue Cross Blue Shield of Michigan, at two time points (2020, 2022). Forty-eight hospitals also submitted sepsis protocols for structured review. SETTING: Multicenter quality improvement consortium. SUBJECTS: Fifty-one hospitals in Michigan. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the included hospitals, 92.2% (n = 47/51) were nonprofit, 88.2% (n = 45/51) urban, 11.8% (n = 6/51) rural, and 80.4% (n = 41/51) teaching hospitals. One hundred percent (n = 51/51) responded to the survey, and 94.1% (n = 48/51) provided a sepsis policy/protocol. All surveyed hospitals used at least one quality improvement approach, including audit/feedback (98.0%, n = 50/51) and/or clinician education (68.6%, n = 35/51). Protocols included the Sepsis-1 (18.8%, n = 9/48) or Sepsis-2 (31.3%, n = 15/48) definitions; none (n = 0/48) used Sepsis-3. All hospitals (n = 51/51) used at least one process to facilitate rapid sepsis treatment, including order sets (96.1%, n = 49/51) and/or stocking of commonly used antibiotics in at least one clinical setting (92.2%, n = 47/51). Treatment protocols included guidance on antimicrobial therapy (68.8%, n = 33/48), fluid resuscitation (70.8%, n = 34/48), and vasopressor administration (62.5%, n = 30/48). On self-assessment, hospitals reported the lowest scores for peridischarge practices, including screening for cognitive impairment (2.0%, n = 1/51 responded “we are good at this”) and providing anticipatory guidance (3.9%, n = 2/51). There were no meaningful associations of the Centers for Medicare and Medicaid Services’ Severe Sepsis and Septic Shock: Management Bundle performance with differences in hospital characteristics or sepsis policy document characteristics. CONCLUSIONS: Most hospitals used audit/feedback, order sets, and clinician education to facilitate sepsis care. Hospitals did not consistently incorporate organ dysfunction criteria into sepsis definitions. Existing processes focused on early recognition and treatment rather than recovery-based practices.
Læs mere Tjek på PubMedLawler, Patrick R.; Manvelian, Garen; Coppi, Alida; Damask, Amy; Cantor, Michael N.; Ferreira, Manuel A. R.; Paulding, Charles; Banerjee, Nilanjana; Li, Dadong; Jorgensen, Susan; Attre, Richa; Carey, David J.; Krebs, Kristi; Milani, Lili; Hveem, Kristian; Damås, Jan K.; Solligård, Erik; Stender, Stefan; Tybjærg-Hansen, Anne; Nordestgaard, Børge G.; Hernandez-Beeftink, Tamara; Rogne, Tormod; Flores, Carlos; Villar, Jesús; Walley, Keith R.; Liu, Vincent X.; Fohner, Alison E.; Lotta, Luca A.; Kyratsous, Christos A.; Sleeman, Mark W.; Scemama, Michel; DelGizzi, Richard; Pordy, Robert; Horowitz, Julie E.; Baras, Aris; Martin, Greg S.; Steg, Philippe Gabriel; Schwartz, Gregory G.; Szarek, Michael; Goodman, Shaun G.
Critical Care Explorations, 11.11.2023
Tilføjet 11.11.2023
OBJECTIVES: Treatments that prevent sepsis complications are needed. Circulating lipid and protein assemblies—lipoproteins play critical roles in clearing pathogens from the bloodstream. We investigated whether early inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) may accelerate bloodstream clearance of immunogenic bacterial lipids and improve sepsis outcomes. DESIGN: Genetic and clinical epidemiology, and experimental models. SETTING: Human genetics cohorts, secondary analysis of a phase 3 randomized clinical trial enrolling patients with cardiovascular disease (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]; NCT01663402), and experimental murine models of sepsis. PATIENTS OR SUBJECTS: Nine human cohorts with sepsis (total n = 12,514) were assessed for an association between sepsis mortality and PCSK9 loss-of-function (LOF) variants. Incident or fatal sepsis rates were evaluated among 18,884 participants in a post hoc analysis of ODYSSEY OUTCOMES. C57BI/6J mice were used in Pseudomonas aeruginosa and Staphylococcus aureus bacteremia sepsis models, and in lipopolysaccharide-induced animal models. INTERVENTIONS: Observational human cohort studies used genetic PCSK9 LOF variants as instrumental variables. ODYSSEY OUTCOMES participants were randomized to alirocumab or placebo. Mice were administered alirocumab, a PCSK9 inhibitor, at 5 mg/kg or 25 mg/kg subcutaneously, or isotype-matched control, 48 hours prior to the induction of bacterial sepsis. Mice did not receive other treatments for sepsis. MEASUREMENTS AND MAIN RESULTS: Across human cohort studies, the effect estimate for 28-day mortality after sepsis diagnosis associated with genetic PCSK9 LOF was odds ratio = 0.86 (95% CI, 0.67–1.10; p = 0.24). A significant association was present in antibiotic-treated patients. In ODYSSEY OUTCOMES, sepsis frequency and mortality were infrequent and did not significantly differ by group, although both were numerically lower with alirocumab vs. placebo (relative risk of death from sepsis for alirocumab vs. placebo, 0.62; 95% CI, 0.32–1.20; p = 0.15). Mice treated with alirocumab had lower endotoxin levels and improved survival. CONCLUSIONS: PCSK9 inhibition may improve clinical outcomes in sepsis in preventive, pretreatment settings.
Læs mere Tjek på PubMedZhenlu Sun, Peihua Niu, Miao Jin, Ruiqing Zhang, Qiao Gao, Hongtao Wang, Xuejun Ma, Ji Wang
Journal of Medical Virology, 11.11.2023
Tilføjet 11.11.2023
Ya‐Ni Zhang, Guang‐Hao Zhu, Wei Liu, Xi‐Xiang Chen, Yuan‐Yuan Xie, Jian‐Rong Xu, Mei‐Fang Jiang, Xiao‐Yu Zhuang, Wei‐Dong Zhang, Hong‐Zhuan Chen, Guang‐Bo Ge
Journal of Medical Virology, 11.11.2023
Tilføjet 11.11.2023
Chia-Jung Kuo, Ngoc-Niem Bui, Jun-Nong Ke, Cheng- Yu Lin, Wey-Ran Lin, Ming-Ling Chang, Hui- Yu Wu, Mei-Zi Huang, Cheng-Hsun Chiu, Cheng-Tang Chiu, Chih-Ho Lai
International Journal of Infectious Diseases, 11.11.2023
Tilføjet 11.11.2023
H. pylori eradication has been recommended to prioritize first-line treatment options such as bismuth quadruple therapy or concomitant therapy, which includes a proton pump inhibitor (PPI), clarithromycin, amoxicillin, and metronidazole. However, this treatment regimen may fail to address infections in up to 20% of patients [1].
Læs mere Tjek på PubMed