Search

Background The adjuvanted respiratory syncytial virus (RSV) prefusion F protein–based vaccine (RSVPreF3 OA) is approved in adults aged ≥60 years. We evaluated RSVPreF3 OA immunogenicity and safety in adults aged 50–59 years without or with increased risk for RSV disease due to specific chronic medical conditions. Methods This observer-blind, phase 3, noninferiority trial included adults aged 50–59 years, stratified into 2 subcohorts: those with and those without predefined, stable, chronic medical conditions leading to an increased risk for RSV disease. Participants in both subcohorts were randomized 2:1 to receive RSVPreF3 OA or placebo. A control group of adults aged ≥60 years received RSVPreF3 OA. Primary outcomes were RSV-A and RSV-B neutralization titers (geometric mean titer ratios and sero-response rate differences) 1 month post-vaccination in 50–59-year-olds versus ≥60-year-olds. Cell-mediated immunity and safety were also assessed. Results The exposed population included 1152 participants aged 50–59 years and 381 participants aged ≥60 years. RSVPreF3 OA was immunologically noninferior in 50–59-year-olds versus ≥60-year-olds; noninferiority criteria were met for RSV-A and RSV-B neutralization titers in those with and those without increased risk for RSV disease. Frequencies of RSVPreF3-specific polyfunctional CD4+ T cells increased substantially from pre- to 1 month post-vaccination. Most solicited adverse events had mild-to-moderate intensity and were transient. Unsolicited and serious adverse event rates were similar in all groups. Conclusions RSVPreF3 OA was immunologically noninferior in 50–59-year-olds compared to ≥60-year-olds, in whom efficacy was previously demonstrated. The safety profile in 50–59-year-olds was consistent with that in ≥60-year-olds. Clinical Trial Registration ClinicalTrials.gov : NCT05590403. [ABSTRACT FROM AUTHOR]

Background Hospital-acquired (HAP) and ventilator-associated pneumonia (VAP) are important complications early (<30 days) after lung transplantation (LT). However, current incidence, associated factors, and outcomes are not well reported. Methods LT recipients transplanted at our institution (July 2019–January 2020 and October 2021–November 2022) were prospectively included. We assessed incidence and presentation of pneumonia and evaluated the impact of associated factors using regression models. We also evaluated molecular relatedness of respiratory pathogens collected peri-transplant and at pneumonia occurrence using pulsed-field gel electrophoresis (PFGE). Results In the first 30 days post-LT, 25/270 (9.3%) recipients were diagnosed with pneumonia (68% [17/25] VAP; 32% [8/25] HAP). Median time to pneumonia was 11 days (IQR, 7–13); 49% (132/270) of donor and 16% (44/270) of recipient respiratory peri-transplant cultures were positive. However, pathogens associated with pneumonia were not genetically related to either donor or recipient cultures at transplant, as determined by PFGE. Diagnosed pulmonary hypertension (HR, 4.42; 95% CI, 1.62–12.08) and immunosuppression use (HR, 2.87; 95% CI, 1.30–6.56) were pre-transplant factors associated with pneumonia. Pneumonia occurrence was associated with longer hospital stay (HR, 5.44; 95% CI, 2.22–13.37) and VAP with longer ICU stay (HR, 4.31; 95% CI, 1.73–10.75) within the first 30 days post-transplantation; 30- and 90-day mortality were similar. Conclusions Prospectively assessed early pneumonia incidence occurred in ∼10% of LT. Populations at increased risk for pneumonia occurrence include LT with pre-transplant pulmonary hypertension and pre-transplant immunosuppression. Pneumonia was associated with increased healthcare use, highlighting the need for further improvements by preferentially targeting higher-risk patients. [ABSTRACT FROM AUTHOR]

Background Obesity is on the rise globally in adults and children, including in tropical areas where diseases such as dengue have a substantial burden, particularly in children. Obesity impacts risk of severe dengue disease; however, the impact on dengue virus (DENV) infection and dengue cases remains an open question. Methods We used 9 years of data from 5940 children in the Pediatric Dengue Cohort Study in Nicaragua to determine whether pediatric obesity is associated with increased susceptibility to DENV infection and symptomatic presentation. Analysis was performed using generalized estimating equations adjusted for age, sex, and preinfection DENV antibody titers. Results From 2011 to 2019, children contributed 26 273 person-years of observation, and we observed an increase in prevalence of overweight (from 12% to 17%) and obesity (from 7% to 13%). There were 1682 DENV infections and 476 dengue cases in the study population. Compared with participants with normal weight, participants with obesity had higher odds of DENV infection (adjusted odds ratio [aOR], 1.21; 95% confidence interval [CI]: 1.03–1.42) and higher odds of dengue in DENV-infected individuals (aOR, 1.59; 95% CI: 1.15–2.19). Children with obesity infected with DENV showed increased odds of presenting fever (aOR, 1.46; 95% CI: 1.05–2.02), headache (aOR, 1.51; 95% CI: 1.07–2.14), and rash (aOR, 2.26; 95% CI: 1.49–3.44) when compared with children with normal weight. Conclusions Our results indicate that obesity is associated with increased susceptibility to DENV infection and dengue cases in children, independent of age, sex, and preinfection DENV antibody titers. [ABSTRACT FROM AUTHOR]

Suppressive antibiotic therapy is prescribed when a patient has an infection that is presumed to be incurable by a defined course of therapy or source control. The cohort receiving suppressive antibiotic therapy is typically highly comorbid and the infections often involve retained prosthetic material. In part due to a lack of clear guidelines regarding the use of suppressive antibiotics, and in part due to the complex nature of the infections in question, patients are often prescribed suppressive antibiotics for extremely long, if not indefinite, courses. The risks of prolonged antibiotic exposure in this context are not fully characterized, but they include adverse drug effects ranging from mild to severe, the development of antibiotic-resistant organisms, and perturbations of the gastrointestinal microbiome. In this narrative review we present the available evidence for the use of suppressive antibiotic therapy in 4 common indications, examine the gaps in the current literature, and explore the known and potential risks of this therapy. We also make suggestions for improving the quality of evidence in future studies, particularly by highlighting the need for a standardized term to describe the use of long courses of antibiotics to suppress hard-to-treat infections. [ABSTRACT FROM AUTHOR]

Neutrophils, the most abundant white blood cells in the human circulation, play crucial roles in various diseases, including kidney disease. Traditionally viewed as short-lived pro-inflammatory phagocytes that release reactive oxygen species, cytokines and neutrophil extracellular traps, recent studies have revealed their complexity and heterogeneity, thereby challenging this perception. Neutrophils are now recognized as transcriptionally active cells capable of proliferation and reverse migration, displaying phenotypic and functional heterogeneity. They respond to a wide range of signals and deploy various cargo to influence the activity of other cells in the circulation and in tissues. They can regulate the behavior of multiple immune cell types, exhibit innate immune memory, and contribute to both acute and chronic inflammatory responses while also promoting inflammation resolution in a context-dependent manner. Here, we explore the origin and heterogeneity of neutrophils, their functional diversity, and the cues that regulate their effector functions. We also examine their emerging role in infectious and non-infectious diseases with a particular emphasis on kidney disease. Understanding the complex behavior of neutrophils during tissue injury and inflammation may provide novel insights, thereby paving the way for potential therapeutic strategies to manage acute and chronic conditions. By deciphering their multifaceted role, targeted interventions can be developed to address the intricacies of neutrophil-mediated immune responses and improve disease outcomes. [ABSTRACT FROM AUTHOR]

This article discusses the recent regulatory restrictions on the use of fluoroquinolones and their impact on treating orthopaedic infections. We focus on the balance between the benefits and risks of fluoroquinolones in scenarios involving severe infections where alternative antibiotics may be less effective. The discussion includes a summary of recent evidence on adverse effects and the implications for clinical practice. [ABSTRACT FROM AUTHOR]

The intestine hosts the largest immune cell compartment in the body as a result of its continuous exposure to exogenous antigens. The intestinal barrier is formed by a single layer of epithelial cells which separate immune cells from the gut lumen. Bidirectional interactions between the epithelium and the immune compartment are critical for maintaining intestinal homeostasis by limiting infection, preventing excessive immune activation, and promoting tissue repair processes. However, our understanding of epithelial–immune interactions incomplete as the complexity of in vivo models can hinder mechanistic studies, cell culture models lack the cellular heterogeneity of the intestine and when established from primary cell can be difficult to maintain. In the last decade, organoids have emerged as a reliable model of the intestine, recapitulating key cellular and architectural features of native tissues. Herein, we provide an overview of how intestinal organoids are being co-cultured with immune cells leading to substantial advances in our understanding of immune–epithelial interactions in the gut. This has enabled new discoveries of the immune contribution to epithelial maintenance and regeneration both in homeostasis and in disease such as chronic inflammation, infection and cancer. Organoids can additionally be used to generate immune cells with a tissue-specific phenotype and to investigate the impact of disease associated risk genes on the intestinal immune environment. Accordingly, this review demonstrates the multitude of applications for intestinal organoids in immunological research and their potential for translational approaches. This review discusses the significance of intestinal organoids as a model for studying immune-epithelial interactions in the gut. Organoids replicate key features of native tissues and have advanced our understanding of the immune system's role in maintaining and regenerating the intestinal barrier during health and disease. The review highlights the various applications of intestinal organoids in immunological research, including co-culturing with immune cells, generating tissue-specific immune cells, and exploring the impact of disease-associated risk genes on the intestinal immune environment. Graphical Abstract [ABSTRACT FROM AUTHOR]

We provide field evidence that individuals engage in motivated optimism in the face of impending risk. Congruent with a dynamic anticipatory utility model, we demonstrate that belief distortions are time and stake dependent. Our study leverages variation in the time span between the survey and the externally imposed date when workers are required to return to their workplaces during the COVID-19 pandemic. We show that, as the work return date approaches, individuals become relatively more optimistic about the increased infection risk associated with going back to the workplace, and about how severely their health may be impacted if they get infected. Belief distortions are larger among those facing potential health complications conditional on infection. Our results are informative about when and for whom interventions will be most effective. [ABSTRACT FROM AUTHOR]

Background To describe reasons for deviations from planned chemotherapy treatments in women with nonmetastatic breast cancer that contribute to less-than-planned receipt of chemotherapy. Methods Electronic medical records for patients receiving chemotherapy were reviewed for adverse events and treatment modifications. Log-binomial regression models were used to estimate relative risks (RRs) with 95% CIs to examine associations between chemotherapy modifications, patient characteristics, and treatment modalities. Results Delays in chemotherapy initiation (7%) were for surgical complications (58%), personal reasons (16%), and other (26%; port malfunction, infections, and obtaining extra imaging). Delays during chemotherapy (38%) were for infections (20%), neutropenia (13%), and personal reasons (13%). Dose reductions (38%) were for neuropathy (36%), unknown causes (9%), anemia (9%), and neutropenia (8%). Early treatment discontinuations (23%) were for neuropathy (29%). Patients receiving paclitaxel/nab-paclitaxel (RR 2.05; 95% CI, 1.47-2.87) and an anthracycline (RR 1.89; 95% CI, 1.39-2.57) reported more dose delays during chemotherapy. Black race (RR 1.46; 95% CI, 1.07-2.00), stage 3 (RR 1.79; 95% CI, 1.09-2.93), and paclitaxel/nab-paclitaxel receipt (RR 1.39; 95% CI, 1.02-1.90) increased the likelihood of dose reduction. Both Black race (RR 2.06; 95% CI, 1.35-3.15) and receipt of paclitaxel/nab-paclitaxel (RR 1.93; 95% CI, 1.19-3.13) increased the likelihood of early discontinuation. Patients receiving anthracyclines had higher rates of hospitalizations during chemotherapy (RR: 1.79; 95% CI, 1.11-2.89). Conclusion Toxicities are the most common reason for treatment modifications and need close monitoring in high-risk groups for timely intervention. Dose reductions and early treatment discontinuations occurred more for Black patients and need further study. [ABSTRACT FROM AUTHOR]

Prior infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is typically measured by nucleocapsid serology assays. In this study, we show that the Simoa serology assay and T-cell intracellular cytokine staining assay are more sensitive than the clinical Elecsys assay for detection of nucleocapsid-specific immune responses. These data suggest that the prevalence of prior SARS-CoV-2 infection in the population may be higher than currently appreciated. [ABSTRACT FROM AUTHOR]

Background: 0.05% Chlorhexidine gluconate (CHG; Irrisept [IrriMax]) is a commercial wound irrigation solution approved by the Food and Drug Administration that has seen recent adoption in the field of prosthetic urology; however, no study has evaluated whether 0.05% CHG is compatible with the minocycline-rifampin–impregnated surface (InhibiZone) of the AMS 700 penile prosthesis (Boston Scientific). Aim: To evaluate whether 0.05% CHG alters the antibiotic efficacy of the minocycline-rifampin–impregnated penile prosthesis surface. Methods: Discs (8 mm) were taken by a punch biopsy (Sklar) from sterile penile prosthesis reservoirs whose surfaces had been impregnated with rifampin and minocycline. Discs (n = 10) were suspended in 0.05% CHG, vancomycin and gentamicin, or normal saline for 2 minutes to simulate intraoperative irrigation. Discs were then rinsed in normal saline to remove any unbound solution and incubated with methicillin-sensitive Staphylococcus aureus for 48 hours. Adherent surface bacteria were suspended by shaking in a 0.3% Tween 20 solution, serially diluted, plated onto 3M PetriFilms, and counted. Kirby-Bauer disc diffusion assays were conducted to generalize findings across various organisms. Outcomes: Outcomes included (1) bacterial adherence to the implant surface measured as bacterial counts (in colony-forming units per milliliter) and (2) bacterial growth reduction measured as zones of inhibitions (in millimeters). Results: Incubation of implant surfaces in 0.05% CHG did not alter recovered bacterial counts as compared with normal saline and vancomycin/gentamycin. Similarly, within a single bacterial species, 0.05% CHG and vancomycin/gentamycin did not alter zone-of-inhibition measurements in Kirby-Bauer disc diffusion studies. Clinical Translation: This study demonstrates in vitro that 0.05% CHG may be used directly on the minocycline-rifampin–impregnated surface without altering the antibiotic efficacy of the coating. Strengths and Limitations: Strengths include that this is the first study to evaluate if 0.05% CHG affected the minocycline-rifampin–impregnated surface. Limitations include the use of in vitro studies, which serve as a proxy for in vivo practices and may not be entirely accurate or translatable in a clinical setting. Conclusion: 0.05% CHG does not alter the antimicrobial activity of the minocycline-rifampin–impregnated surface as compared with vancomycin/gentamycin and normal saline in vitro; however, its efficacy in clinical practice remains to be evaluated. [ABSTRACT FROM AUTHOR]

Background: Chlorhexidine gluconate (CHG) (0.05%) has recently been suggested as both a dip for the hydrophilic surface and an irrigation solution in the setting of penile prosthesis (PP) surgery. Aim: The study sought to compare the antimicrobial efficacy of 0.05% CHG with vancomycin and gentamicin (VG) antibiotics as dip and/or irrigation solutions in the setting of a hydrophilic PP surface in vitro. Methods: Sterile PPs with a hydrophilic coating were obtained. A series of experiments were performed to evaluate the efficacy of normal saline (NS), 0.05% CHG, or VG as dip and/or irrigation solutions to reduce methicillin-sensitive Staphylococcus aureus adhesion to PP surfaces. The 8-mm discs from PPs were incubated in 105 colony-forming units/mL of methicillin-sensitive S aureus for 48 hours, plated, and counted. Disc-diffusion tests were conducted by suspending 6-mm discs for 2 minutes in NS, 0.05% CHG, or VG, then placing them coated side down onto plates streaked with the following organisms: methicillin-sensitive S aureus, S epidermidis, Enterococcus, and Escherichia coli. After 24 hours of growth, zones of inhibition were measured. Outcomes: We found average bacterial counts (colony-forming units/mL) and zones of inhibition (mm) following a series of treatment protocols of PP discs. Results: PP discs dipped in VG reduced bacterial adhesion to the implant surface >0.05% CHG (~5.5 log vs ~1.5 log; P < .01). Discs irrigated with either 0.05% CHG or NS removed all dip solution adsorbed to the hydrophilic surface, allowing bacterial growth. VG irrigation adsorbed to the hydrophilic surface even after 0.05% CHG or NS dips, reducing bacterial adherence (~3 log). Dipping and irrigating discs with VG was most effective in reducing adherent bacteria (~5.5 log) and was the only irrigation that showed antimicrobial activity. Clinical Translation: VG, when used both as a prophylactic dip and as an intraoperative irrigation solution for hydrophilic penile implant surfaces, has improved efficacy to 0.05% CHG and NS. Strengths and Limitations: This is the first study to compare the use of VG, 0.05% CHG, and NS as prophylactic dips and intraoperative irrigations for hydrophilic penile implant surfaces. Limitations include the use of in vitro studies, which serve as a proxy for in vivo practices and may not be entirely accurate nor translatable clinically. Conclusion: We demonstrated the superior efficacy of VG as a combined dip and irrigation solution for hydrophilic penile implant surfaces compared with 0.05% CHG. [ABSTRACT FROM AUTHOR]

Background Many patients with hematological malignancy develop fever after chemotherapy/conditioning but before chemotherapy-induced neutropenia (preneutropenic fever [PNF]). The proportion of PNF with an infectious etiology is not well established. Methods We conducted a single-center, prospective observational substudy of PNF (neutrophils >0.5 cells/μL, ≥38.0°C) in adults receiving acute myeloid leukemia (AML) chemotherapy, or allogeneic hematopoietic cell transplant (allo-HCT) conditioning enrolled in a neutropenic fever randomized controlled trial between 1 January and 31 October 2018. Eligible patients had anticipated neutropenia ≥10 days and exclusions included concurrent infection and/or neutropenia prior to chemotherapy or conditioning. PNF rates and infections encountered were described. Associations between noninfectious etiologies and fever were explored. Antimicrobial therapy prescription across preneutropenic and neutropenic periods was examined. Results Of 62 consecutive patients included (43 allo-HCT, 19 AML), 27 had PNF (44%) and 5 (19%) had an infective cause. Among allo-HCT, PNF occurred in 14 of 17 (82%) who received thymoglobulin; only 1 of 14 (7%) had infection. During AML chemotherapy, 18 of 19 received cytarabine, of which 8 of 18 (44%) had PNF and 3 of 8 (38%) had infection. Most patients with PNF had antimicrobial therapy continued into the neutropenic period (19/27 [70%]). Those with PNF were more likely to be escalated to broader antimicrobial therapy at onset/during neutropenic fever (5/24 [21%] vs 2/30 [7%]). Conclusions Rates of PNF were high, and documented infection low, leading to prolonged and escalating antimicrobial therapy. In the absence of infection, early cessation of empiric therapy after PNF is recommended as an important stewardship intervention. [ABSTRACT FROM AUTHOR]

Infections remain a major concern following bispecific antibody therapy but are not well described in pivotal trials. We present the first well-documented case of a classic but rare opportunistic infection, disseminated Mycobacterium avium complex, in a patient receiving bispecific antibody therapy. [ABSTRACT FROM AUTHOR]

Transposable elements make up substantial proportions of eukaryotic genomes and many are thought to be remnants of ancient viral infections. Current research has begun to highlight the role transposable elements can play in the immune system response to infections. However, most of our knowledge about transposable element expression during infection is limited by the specific host and pathogen factors from each study, making it difficult to compare studies and develop broader patterns regarding the role of transposable elements during infection. Here, we use the tools and resources available in the model, Drosophila melanogaster , to analyze multiple gene expression datasets of flies subject to bacterial, fungal, and viral infections. We analyzed differences in pathogen species, host genotype, host tissue, and sex to understand how these factors impact transposable element expression during infection. Our results highlight both shared and unique transposable element expression patterns between pathogens and suggest a larger effect of pathogen factors over host factors for influencing transposable element expression. [ABSTRACT FROM AUTHOR]

Lupus nephritis (LN) is one of the most severe clinical manifestations of systemic lupus erythematosus (SLE). Notably, the clinical manifestations of LN are not always consistent with the histopathological findings. Therefore, the diagnosis and activity monitoring of this disease are challenging and largely depend on invasive renal biopsy. Renal biopsy has side effects and is associated with the risk of bleeding and infection. There is a growing interest in the development of novel noninvasive biomarkers for LN. In this review, we summarize most of the LN biomarkers discovered so far by correlating current knowledge with future perspectives. These biomarkers fundamentally reflect the biological processes of kidney damage and repair during disease. Furthermore, this review highlights the role of urinary cell phenotype detection in the diagnosis, monitoring, and treatment of LN and summarizes the limitations and countermeasures of this test. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the effectiveness and safety of two different intravenous methylprednisolone (IVMP) pulse doses in patients with severe microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Methods We emulated a target trial using observational data from the nationwide registry in Japan. Patients with severe glomerulonephritis or diffuse alveolar haemorrhage were selected and pseudo-randomized into three groups using propensity score-based overlap weighting as follows: non-IVMP, IVMP 0.5 g/day and IVMP 1.0 g/day. The primary outcome was all-cause mortality, and the secondary outcomes were composite all-cause mortality and kidney failure, severe relapse and serious infection from 2 to 48 weeks after treatment initiation. To estimate the treatment effects, the Cox proportional hazard model and Fine–Gray subdistribution hazard model were used. Results In this emulated target trial, of 201 eligible patients (MPA, 175; GPA, 26), 6 (3%) died, 4 (2.0%) had kidney failure, 11 (5.5%) had severe relapse, and 40 (19.9%) had severe infections. Hazard ratios (HR) for IVMP 0.5 g/day and IVMP 1.0 g/day pulse groups compared with non-IVMP pulse were as follows: all-cause mortality 0.46 (95% CI: 0.07, 2.81) and 0.07 (95% CI: 0.01, 0.41), respectively; all-cause mortality/kidney failure 1.18 (95% CI: 0.26, 5.31) and 0.59 (95% CI: 0.08, 4.52), respectively; subdistribution HRs for severe relapse were 1.26 (95% CI: 0.12, 13.70) and 3.36 (95% CI: 0.49, 23.29), respectively; and for serious infection 1.88 (95% CI: 0.76, 4.65) and 0.94 (95% CI: 0.28, 3.13), respectively. Conclusion IVMP 1.0 g/day pulse may improve 48-week mortality in patients with severe MPA/GPA. [ABSTRACT FROM AUTHOR]

Background Polymicrobial pericarditis is an extremely rare and lethal form of pericarditis. Prompt initiation of appropriate antimicrobial treatment and pericardial drainage are crucial. Case summary A 57-year-old immunocompromised male patient presented to the emergency department due to dyspnoea, chest pain, and fever lasting for 7 days. Following clinical, laboratory, and imaging work-up, he was found to have pericardial effusion with signs of tamponade. After pericardiocentesis through subxiphoid and apical approaches, 800 mL of gross purulent fluid was obtained. Blood and pericardial fluid cultures confirmed the diagnosis of polymicrobial purulent pericarditis (Staphylococcus aureus and Bacteroides vulgatus). Further work-up revealed minor peritoneal effusion, and paracentesis fluid culture revealed the presence of S. aureus and, additionally, Candida albicans. After treatment initiation with intravenous antibiotics, pericardial, drainage and supportive measures, the patient's condition initially improved despite the development of constrictive pericarditis. However, he suddenly deteriorated after 37 days of hospitalization and passed away after 51 days of hospitalization. Discussion To the best of our knowledge, this is the first report of purulent pericarditis and purulent peritoneal effusion in the settings of S. aureus bacteraemia with an absent primary infection focus. Clinicians should be aware of treatment options for purulent pericarditis and consider intrapericardial fibrinolysis, especially in patients not suited for more invasive pericarditis treatment. [ABSTRACT FROM AUTHOR]

Background The pathogenesis of atopic dermatitis (AD) remains unclear. Nontyphoidal Salmonella (NTS) infection might trigger immune-mediated reactions. We aimed to examine NTS and the risk of subsequent AD. Methods From 2002 to 2015, eligible patients (aged 0–100 years) with NTS were identified. NTS and non-NTS groups were matched at a 1:10 ratio on age and sex. We utilized conditional multivariable Cox proportional hazard models to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for AD development. Subgroup analyses were conducted based on age, sex, and severity of NTS infection. We utilized landmark analysis to explore the time-dependent hazard of AD following NTS. Results In the NTS group (N = 6624), 403 developed AD. After full adjustment of demographics and comorbidities, the NTS group had a higher risk of AD than the reference group (aHR = 1.217, 95% CI = 1.096–1.352). Age-stratified analysis revealed that NTS group exhibited an elevated risk compared to the reference group, particularly among those aged 13–30 years (aHR = 1.25, 95% CI = 1.017–1.559), individuals aged 31–50 years (aHR = 1.388, 95% CI = 1.112–1.733), those aged 51–70 years (aHR = 1.301, 95% CI = 1.008–1.679), and individuals aged 71 years and over (aHR = 1.791, 95% CI = 1.260–2.545). Severe NTS was associated with a higher risk of AD than the reference group (aHR = 2.411, 95% CI = 1.577–3.685). Landmark analysis showed generally consistent findings. Conclusions Minimizing exposure to NTS infection may represent a prospective strategy for averting the onset and progression of atopic dermatitis. Key messages What is already known on this topic AD is particularly susceptible to affronts from the environment. NTS infection has been associated with dysbiosis and autoimmune reactions, which may have a common pathogenesis with AD. What this study adds NTS had a higher risk of AD than the reference group. Additionally, this risk was even more pronounced in those with severe NTS. How this study might affect research, practice, or policy Minimizing exposure to NTS infection could be a potential strategy for preventing the onset and progression of AD. The study offers a promising avenue for further investigation into the underlying pathogenesis of AD. [ABSTRACT FROM AUTHOR]

Background Outbreaks of vaccine-preventable diseases (VPDs) in healthcare workers (HCWs) can result in morbidity and mortality and cause significant disruptions to healthcare services, patients, and visitors as well as an added burden on the healthcare system. This scoping review aimed to describe the epidemiology of VPD outbreaks in HCWs caused by diseases that are prevented by the 10 vaccines recommended by the World Health Organization for HCWs. Methods In April 2022, CINAHL, MEDLINE, Global Health, and EMBASE were searched for all articles reporting on VPD outbreaks in HCWs since the year 2000. Articles were included regardless of language and study type. Clinical and epidemiological characteristics of VPD outbreaks were described. Results Our search found 9363 articles, of which 216 met the inclusion criteria. Studies describing 6 of the 10 VPDs were found: influenza, measles, varicella, tuberculosis, pertussis, and rubella. Most articles (93%) were from high- and upper-middle-income countries. While most outbreaks occurred in hospitals, several influenza outbreaks were reported in long-term-care facilities. Based on available data, vaccination rates among HCWs were rarely reported. Conclusions We describe several VPD outbreaks in HCWs from 2000 to April 2022. The review emphasizes the need to understand the factors influencing outbreaks in HCWs and highlights the importance of vaccination among HCWs. [ABSTRACT FROM AUTHOR]

Point-of-care ultrasound (POCUS) is a safe, noninvasive technique performed at the patient's bedside, providing immediate results to the operator. It complements physical examination and facilitates clinical decision-making. In infectious diseases, POCUS is particularly valuable, offering an initial assessment in cases of suspected infection. It often leads to an early tentative diagnosis enabling the prompt initiation of antimicrobial treatment without the delay associated with traditional radiology. POCUS provides direct visualization of affected organs, assists in evaluating fluid balance, and facilitates various interventions, all while reducing patient discomfort. For infectious disease specialists, becoming proficient in POCUS is a critical future challenge, requiring dedicated training for effective utilization. [ABSTRACT FROM AUTHOR]

During pandemics, healthcare providers struggle with balancing obligations to self, family, and patients. While HIV/AIDS seemed to settle this issue, coronavirus disease 2019 (COVID-19) rekindled debates regarding treatment refusal. We searched MEDLINE, Embase, CINAHL Complete, and Web of Science using terms including obligation, refusal, HIV/AIDS, COVID-19, and pandemics. After duplicate removal and dual, independent screening, we analyzed 156 articles for quality, ethical position, reasons, and concepts. Diseases in our sample included HIV/AIDS (72.2%), severe acute respiratory syndrome (SARS) (10.2%), COVID-19 (10.2%), Ebola (7.0%), and influenza (7.0%). Most articles (81.9%, n = 128) indicated an obligation to treat. COVID-19 had the highest number of papers indicating ethical acceptability of refusal (60%, P <.001), while HIV had the least (13.3%, P =.026). Several reason domains were significantly different during COVID-19, including unreasonable risks to self/family (26.7%, P <.001) and labor rights/workers' protection (40%, P <.001). A surge in ethics literature during COVID-19 has advocated for permissibility of treatment refusal. Balancing healthcare provision with workforce protection is crucial in effectively responding to a global pandemic. [ABSTRACT FROM AUTHOR]

M1UK is associated with current surges in invasive infection globally, partly due to increased production of superantigen streptococcal pyrogenic exotoxin A. We show that M1UK is now the dominant invasive emm 1 lineage in Aotearoa New Zealand and is genomically related to community infections, suggesting that measures that effectively prevent group A Streptococcus pharyngitis in children could reduce invasive disease. [ABSTRACT FROM AUTHOR]

Cardiac implantable electronic device infection in the context of corynebacterial bloodstream infection (BSI) remains poorly understood. From 2012 to 2023 at Mayo Clinic, 4 of 12 patients with corynebacterial BSI had cardiac implantable electronic device infection: 1 patient was diagnosed during a relapsing BSI episode. Undefined source, persistent BSI, and the presence of a prosthetic cardiac valve were common characteristics. [ABSTRACT FROM AUTHOR]

Background Advanced age has been widely identified as a risk factor for recurrent Clostridioides difficile infection (CDI), but most related studies were performed before the introduction of novel therapies. The aim of this study was to compare CDI characteristics and outcomes in patients over and under 80 years old with CDI and their outcomes in the era of new treatments. Methods This was a retrospective cohort study of patients diagnosed with CDI from January 2021 to December 2022 in an academic hospital. We compared recurrence and mortality at 12 weeks after the end of treatment. An extension of the Fine and Grey model adjusted for competing events was used to assess the effect of age on recurrence. Results Four hundred seventy-six patients were considered to have CDI (320 in patients <80 years and 156 in ≥80 years). CDI in older patients was more frequently healthcare-associated and was more severe. Although the Charlson index was almost identical between populations, comorbidities clearly differed. New treatments (bezlotoxumab, fidaxomicin and faecal microbiota transplantation) were more frequently used in older patients without statistical significance (41.3% vs. 33.4%, P  = .053). There were 69 (14.5%) recurrences, with no differences by age group after adjusting for competing events. Mortality was greater in the oldest (35.3%) than in the youngest (13.1%); P  < .001. Conclusions No differences in CDI recurrence rates were found between age groups. However, there was a high mortality rate in patients ≥80 years old, which emphasises the urgent need to improve the prevention and treatment of CDI in this group. [ABSTRACT FROM AUTHOR]

Background Numerous studies demonstrate associations between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases. Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population. The benefit-risk ratio of this increase in vitamin D use is not clear, and the optimal vitamin D intake and the role of testing for 25(OH)D for disease prevention remain uncertain. Objective To develop clinical guidelines for the use of vitamin D (cholecalciferol [vitamin D3] or ergocalciferol [vitamin D2]) to lower the risk of disease in individuals without established indications for vitamin D treatment or 25(OH)D testing. Methods A multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, identified and prioritized 14 clinically relevant questions related to the use of vitamin D and 25(OH)D testing to lower the risk of disease. The panel prioritized randomized placebo-controlled trials in general populations (without an established indication for vitamin D treatment or 25[OH]D testing), evaluating the effects of empiric vitamin D administration throughout the lifespan, as well as in select conditions (pregnancy and prediabetes). The panel defined "empiric supplementation" as vitamin D intake that (a) exceeds the Dietary Reference Intakes (DRI) and (b) is implemented without testing for 25(OH)D. Systematic reviews queried electronic databases for publications related to these 14 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and guide recommendations. The approach incorporated perspectives from a patient representative and considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations. The process to develop this clinical guideline did not use a risk assessment framework and was not designed to replace current DRI for vitamin D. Results The panel suggests empiric vitamin D supplementation for children and adolescents aged 1 to 18 years to prevent nutritional rickets and because of its potential to lower the risk of respiratory tract infections; for those aged 75 years and older because of its potential to lower the risk of mortality; for those who are pregnant because of its potential to lower the risk of preeclampsia, intra-uterine mortality, preterm birth, small-for-gestational-age birth, and neonatal mortality; and for those with high-risk prediabetes because of its potential to reduce progression to diabetes. Because the vitamin D doses in the included clinical trials varied considerably and many trial participants were allowed to continue their own vitamin D–containing supplements, the optimal doses for empiric vitamin D supplementation remain unclear for the populations considered. For nonpregnant people older than 50 years for whom vitamin D is indicated, the panel suggests supplementation via daily administration of vitamin D, rather than intermittent use of high doses. The panel suggests against empiric vitamin D supplementation above the current DRI to lower the risk of disease in healthy adults younger than 75 years. No clinical trial evidence was found to support routine screening for 25(OH)D in the general population, nor in those with obesity or dark complexion, and there was no clear evidence defining the optimal target level of 25(OH)D required for disease prevention in the populations considered; thus, the panel suggests against routine 25(OH)D testing in all populations considered. The panel judged that, in most situations, empiric vitamin D supplementation is inexpensive, feasible, acceptable to both healthy individuals and health care professionals, and has no negative effect on health equity. Conclusion The panel suggests empiric vitamin D for those aged 1 to 18 years and adults over 75 years of age, those who are pregnant, and those with high-risk prediabetes. Due to the scarcity of natural food sources rich in vitamin D, empiric supplementation can be achieved through a combination of fortified foods and supplements that contain vitamin D. Based on the absence of supportive clinical trial evidence, the panel suggests against routine 25(OH)D testing in the absence of established indications. These recommendations are not meant to replace the current DRIs for vitamin D, nor do they apply to people with established indications for vitamin D treatment or 25(OH)D testing. Further research is needed to determine optimal 25(OH)D levels for specific health benefits. [ABSTRACT FROM AUTHOR]

Objective: Infections are a critical concern for patients with microscopic polyangiitis (MPA). This study aimed to identify the risk factors associated with serious infections (SIs) and infection-related mortality in patients with MPA, as well as the effect of glucocorticoid (GC) dose tapering on these outcomes. Methods: This multicentre, retrospective, and observational study utilised data from a cohort of patients with MPA in Japan [Registry of Vasculitis Patients to Establish REAL World Evidence (REVEAL) cohort]. Patients were categorised based on the occurrence of SIs or infection-related deaths, and various characteristics were compared among the groups. Results: Among 182 patients, 66 (36.2%) experienced 129 SIs and 27 (14.8%) developed infection-related deaths. Advanced age, elevated C-reactive protein (CRP) levels, and higher ratio of the GC dose at 3 months to the initial dose were identified as independent risk factors for SIs. Older age was also associated with infection-related deaths. Furthermore, the cumulative incidence of infection-related deaths was significantly higher in patients with a higher ratio of the GC dose at 24 months to the initial dose. Conclusion: Older age, elevated CRP levels, and slower GC dose tapering predispose patients to SIs and infection-related deaths. Strategies, such as rapid GC dose tapering, are anticipated to mitigate the risk of infections. [ABSTRACT FROM AUTHOR]

Background Local institutional guidelines and order sets were updated in June 2023 to recommend first-line cefoxitin monotherapy for the treatment of intra-amniotic infections (IAIs) and endometritis. This study evaluated the clinical impact of this change. Methods This was a retrospective, observational cohort study in an 11-campus health system comparing clinical outcomes of patients with chorioamnionitis, endometritis, or septic abortion receiving intravenous antimicrobial therapy before and after implementation of first-line cefoxitin monotherapy recommendations for the treatment of these infections. Primary outcome was a composite of serious clinical events postdelivery (ie, intensive care unit admission, death, hospital readmission related to IAI or endometritis within 30 days, additional surgery or procedures, or deep surgical site infection). Baseline characteristics between the pre- and post-cefoxitin groups were compared via Student's t tests for continuous variables and chi-square tests for categorical variables. Outcomes were evaluated via generalized linear modeling. Results A total of 472 patients were enrolled, 350 (74%) in the pre-cefoxitin group and 122 (26%) in the post-cefoxitin group. Groups were significantly different by race, healthcare payor, and hospital campus. Cefoxitin was rarely used in the pre-cefoxitin group (n = 2, <0.1%) and commonly used in the post-cefoxitin group (n = 112, 91.8%). After controlling for group differences, odds of experiencing serious clinical event postdelivery in the post-cefoxitin group were noninferior to those in the pre-cefoxitin group (adjusted odds ratio,.37; 95% CI,.17–.76; P =.010). Conclusions Local institutional guidelines with predominant use of cefoxitin therapy were noninferior to traditional antimicrobial therapy regimens for the treatment of IAI. [ABSTRACT FROM AUTHOR]

Undernutrition is the leading risk factor for tuberculosis (TB) globally and in India. This multicenter prospective cohort analysis from India suggests that undernutrition is associated with increased risk of TB disease but not TB infection among household contacts of persons with TB. [ABSTRACT FROM AUTHOR]

Background People with human immunodeficiency virus (PWH) with recurrent visceral leishmaniasis (VL) could potentially drive Leishmania transmission in areas with anthroponotic transmission such as East Africa, but studies are lacking. Leishmania parasitemia has been used as proxy for infectiousness. Methods This study is nested within the Predicting Visceral Leishmaniasis in HIV-InfectedPatients (PreLeisH) prospective cohort study, following 490 PWH free of VL at enrollment for up to 24–37 months in northwest Ethiopia. Blood Leishmania polymerase chain reaction (PCR) was done systematically. This case series reports on 10 PWH with chronic VL (≥3 VL episodes during follow-up) for up to 37 months, and 3 individuals with asymptomatic Leishmania infection for up to 24 months. Results All 10 chronic VL cases were male, on antiretroviral treatment, with 0–11 relapses before enrollment. Median baseline CD4 count was 82 cells/µL. They displayed 3–6 VL treatment episodes over a period up to 37 months. Leishmania blood PCR levels were strongly positive for almost the entire follow-up (median cycle threshold value, 26 [interquartile range, 23–30]), including during periods between VL treatment. Additionally, we describe 3 PWH with asymptomatic Leishmania infection and without VL history, with equally strong Leishmania parasitemia over a period of up to 24 months without developing VL. All were on antiretroviral treatment at enrollment, with baseline CD4 counts ranging from 78 to 350 cells/µL. Conclusions These are the first data on chronic parasitemia in PWH from Leishmania donovani –endemic areas. PWH with asymptomatic and symptomatic Leishmania infection could potentially be highly infectious and constitute Leishmania superspreaders. Xenodiagnosis studies are required to confirm infectiousness. [ABSTRACT FROM AUTHOR]

Background This study aimed to describe documented infections associated with postinfusion fever after CAR T-cell therapy and to evaluate daily changes in vital signs, laboratory results, and the National Early Warning Score (NEWS) in patients with and without confirmed bacterial infections following fever onset, with the objective of assisting in antibiotic stewardship. Methods This was a retrospective, observational study including all consecutive adult patients who received CAR T-cell therapy. Documented infection in the first fever episode after infusion, and clinical and analytic trend comparison of patients with bacterial documented infections and those without documented infections, are described. Results Among 152 patients treated with CAR T-cell therapy, 87 (57.2%) had fever within 30 days of infusion, with a median time from infusion to fever of 3 (interquartile range, 2–5) days. Of these 87 patients, 82 (94.3%) received broad-spectrum antibiotics. Infection was documented in 9 (10.3%) patients and only 4 (4.6%) had bacterial infections. Clinical signs and biomarkers were similar in patients with bacterial documented infection and in those without documented infection at fever onset. Fever, tachycardia, and high C-reactive protein levels remained high during the first 3 days after CAR T-cell infusion, even when no infection was documented. Conclusions Fever is a common symptom following CAR T-cell infusion and is largely treated with broad-spectrum antibiotics. However, confirmed bacterial documented infections after the first fever post–CAR T-cell infusion are very unusual. Because clinical parameters and biomarkers are not useful for identifying infectious fever, other methods should be assessed to ensure the proper use of antibiotics. [ABSTRACT FROM AUTHOR]

Hospitalizations are increasing among persons who use opioids, secondary to overdose and infections. Our study identified acute hospitalization as a reachable moment for engaging people who use drugs in increased screening and education about human immunodeficiency virus risk and prevention (preexposure prophylaxis). [ABSTRACT FROM AUTHOR]

The emergence of new infectious diseases poses a major threat to humans, animals, and broader ecosystems. Defining factors that govern the ability of pathogens to adapt to new host species is therefore a crucial research imperative. Pathogenic bacteria are of particular concern, given dwindling treatment options amid the continued expansion of antimicrobial resistance. In this review, we summarize recent advancements in the understanding of bacterial host species adaptation, with an emphasis on pathogens of humans and related mammals. We focus particularly on molecular mechanisms underlying key steps of bacterial host adaptation including colonization, nutrient acquisition, and immune evasion, as well as suggest key areas for future investigation. By developing a greater understanding of the mechanisms of host adaptation in pathogenic bacteria, we may uncover new strategies to target these microbes for the treatment and prevention of infectious diseases in humans, animals, and the broader environment. [ABSTRACT FROM AUTHOR]

Objectives: This article aims to examine the ability of the Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) risk score to predict the occurrence of serious infections in Japanese patients with rheumatoid arthritis (RA), after initiating their first biologic disease–modifying antirheumatic drug (bDMARD). Methods: We used data from the Institute of Rheumatology, Rheumatoid Arthritis cohort from 2008 to 2020. Patients with RA who were started on their first bDMARDs were included. Those with missing data required to calculate the score were excluded. A receiver operating characteristic curve was used to evaluate the discriminatory ability of the RABBIT score. Results: A total of 1081 patients were enrolled. During the 1-year observational period, 23 (1.7%) patients had serious infections; the most frequent one was bacterial pneumonia (n = 11, 44%). The median RABBIT score in the serious infection group was significantly higher than that in the non-serious infection group [2.3 (1.5–5.4) vs 1.6 (1.2–2.5), P < .001]. The area under the receiver operating characteristic curve for the occurrence of serious infections was 0.67 (95% confidence interval 0.52–0.79), suggesting that the score had low accuracy. Conclusions: Our present study revealed that the RABBIT risk score did not have sufficient discriminatory ability for predicting the development of severe infections in Japanese patients with RA after initiating their first bDMARD. [ABSTRACT FROM AUTHOR]

Aim The high incidence of virus-related infections and the large diffusion of drug-resistant pathogens stimulate the search and identification of new antiviral agents with a broad spectrum of action. Antivirals can be designed to act on a single target by interfering with a specific step in the viral lifecycle. On the contrary, antiviral peptides (AVPs) are known for acting on a wide range of viruses, with a diversified mechanism of action targeting virus and/or host cell. In the present study, we evaluated the antiviral potential of the peptide Hylin-a1 secreted by the frog Hypsiobas albopunctatus against members of the Herpesviridae family. Methods and Results The inhibitory capacity of the peptide was evaluated in vitro by plaque assays in order to understand the possible mechanism of action. The results were also confirmed by real-time PCR and Western blot evaluating the expression of viral genes. Hylin-a1 acts to block the herpetic infection interfering at the early stages of both herpes simplex virus type 1 (HSV-1) and type 2 infection. Its mechanism is mainly directed on the membrane, probably by damaging the viral envelope. The same effect was also observed against HSV-1 strains resistant to acyclovir. Conclusions The data presented in this study, such as the increased activity of the peptide when combined to acyclovir, a weak hemolytic profile, an anti-inflammatory effect, and a tolerable half-life in serum, indicates Hylin-a1 as a novel antiherpetic molecule with promising potential in the clinical setting. [ABSTRACT FROM AUTHOR]

Aims A severe lockdown occurred in Wuhan during the COVID-19 pandemic, followed by a remission phase in the pandemic's aftermath. This study analyzed the bacterial and fungal profiles of respiratory pathogens in patients hospitalized with non-COVID-19 lower respiratory tract infections (LRTIs) during this period to determine the pathogen profile distributions in different age groups and hospital departments in Wuhan. Methods and results We collected reports of pathogen testing in the medical records of patients hospitalized with non-COVID-19 LRTI between 2019 and 2021. These cases were tested for bacterial and fungal pathogens using 16S and internal transcribed spacer sequencing methods on bronchoalveolar lavage fluid samples. The study included 1368 cases. The bacteria most commonly identified were Streptococcus pneumoniae (12.50%) and Mycoplasma pneumoniae (8.33%). The most commonly identified fungi were Aspergillus fumigatus (2.49%) and Pneumocystis jirovecii (1.75%). Compared to 2019, the S. pneumoniae detection rates increased significantly in 2021, and those of M. pneumoniae decreased. Streptococcus pneumoniae was detected mainly in children. The detection rates of almost all fungi were greater in the respiratory Intensive Care Unit compared to respiratory medicine. Streptococcus pneumoniae and M. pneumoniae were detected more frequently in the pediatric department. Conclusions Before and after the COVID-19 outbreak, a change in the common pathogen spectrum was detected in patients with non-COVID-19 in Wuhan, with the greatest change occurring among children. The major pathogens varied by the patient's age and the hospital department. [ABSTRACT FROM AUTHOR]

Wound infection is the most common complication among pediatric burn patients. When not treated promptly, burn wound infection may lead to delayed healing, failure of skin grafts, or death. Standard burn wound assessment includes inspection for visual signs and symptoms of infection (VSSI) and microbial sampling. To aid in the assessment of burn wound infection, the MolecuLight, a point-of-care autofluorescence imaging device, was introduced at our pediatric burn program in 2020. The MolecuLight uses violet light to illuminate the wound bed, causing clinically relevant quantities of 29 different species of bacteria (>104 CFU/g) to fluoresce in real time. The objectives of this study were to evaluate the role of the MolecuLight in the management of pediatric burn wounds and determine if the findings from the MolecuLight corresponded to VSSI and/or microbial sampling. A retrospective review of patients 0-18 years who had burn wounds assessed with the MolecuLight between November 1, 2020 and June 8, 2023 was conducted. Data were extracted from the medical records of 178 eligible patients with 218 wounds imaged with the device. Fluorescence corresponded with VSSI in 81% of wounds and microbial findings in 82% of wounds. MolecuLight fluorescence, in combination with VSSI, improved sensitivity for detecting wound infections by 39% and decreased specificity by 19% compared to visual signs and symptoms in isolation. Incorporation of the MolecuLight in standard burn wound assessments can improve the detection of infections, which may promote improved wound healing outcomes and antimicrobial stewardship. [ABSTRACT FROM AUTHOR]

The association between persistent gram-negative bloodstream infection (GN-BSI), or ongoing positive cultures, and recurrent GN-BSI has not been investigated. Among 992 adults, persistent GN-BSI was associated with increased recurrent GN-BSI with the same bacterial species and strain (6% vs 2%; P =.04). Persistent GN-BSI may be a marker of complicated infection. [ABSTRACT FROM AUTHOR]

We are currently witnessing the endemization of urogenital schistosomiasis in southern Europe. The incriminated parasite is a hybrid between a human parasite and a livestock parasite. Using an experimental evolutionary protocol, we created hybrid lines from pure strains of both parasite species. We showed that the host spectrum of the human parasite is enlarged to the livestock parasite after genomic introgression. We also evidenced that the tropism of the parasites within the host changes and that some hybrid lines are more virulent than the parental strains. These results engage a paradigm shift from human to zoonotic transmission of urogenital schistosomiasis. [ABSTRACT FROM AUTHOR]

A large body of evidence suggests that low parasite carriage in Plasmodium falciparum asymptomatic infection is required for the maintenance of malaria immunity. However, the fact that treating such infections has little to no impact on subsequent clinical malaria is rarely noted. In this paper, we review data and argue that low-density parasite carriage in asymptomatic infection may not support host immune processes and that parasites are virtually under the host's immunological radar. We also discuss factors that may be constraining parasitemia in asymptomatic infections from reaching the threshold required to cause clinical symptoms. A thorough understanding of this infectious reservoir is essential for malaria control and eradication because asymptomatic infections contribute significantly to Plasmodium transmission. [ABSTRACT FROM AUTHOR]

Background Vascular graft infection (VGI) is a serious complication after implantation of arterial vascular grafts. Optimal surgical and pathogen-specific antimicrobial treatment regimens for VGI are largely unknown. We evaluated patients with arterial VGI according to onset, location, microbiological and imaging characteristics, and surgical and antimicrobial treatment and performed an outcome evaluation. Methods Consecutive patients with VGI treated in 2 hospitals from 2010 through 2020 were retrospectively analyzed. Uniform definition criteria and standardized outcome evaluation were applied. Logistic regression was used for multiple analysis; survival analysis was performed with Kaplan-Meier analysis and a log-rank test. Results Seventy-eight patients with VGI were included: 30 early-onset cases (<8 weeks after graft implantation) and 48 late-onset cases, involving 49 aortic and 29 peripheral grafts. The median time from initial implantation to diagnosis of VGI was significantly longer in aortic than peripheral VGIs (363 vs 56 days, P =.018). Late-onset VGI (odds ratio [OR], 7.3; P =.005) and the presence of surgical site infection/complication (OR, 8.21; P =.006) were independent risk factors for treatment failure. Surgical site infection/complication was associated with a higher risk for early-onset VGI (OR, 3.13; P =.040). Longer infection-free survival was observed in cases where the infected graft was surgically removed (P =.037). Conclusions This study underlines the importance of timely diagnosis of VGI and preventing surgical site infections/complications at graft implantation. It highlights the complexity of infection eradication, especially for late-onset infections, and the importance of adequate antimicrobial and surgical treatment. [ABSTRACT FROM AUTHOR]

A recent study examined the prescribing practices for diabetic foot infections (DFIs) in the United States. The study found that there was a high rate of discordant use of antipseudomonal therapy compared to the actual prevalence of Pseudomonas aeruginosa (PsA) in culture. Risk factors for PsA isolation included immunocompromised status and previous outpatient treatment failure. The study suggests that antimicrobial stewardship programs should focus on avoiding unnecessary antipseudomonal antibiotics and emphasizes the need for surgical interventions and preventative care in addition to empiric antibiotic treatment. [Extracted from the article]

Echinococcus multilocularis , the fox dwarf tapeworm, causes alveolar echinococcosis (AE), a critical and life-threatening condition. A radical surgical approach represents the only curative option. In this case study, we present a 37-year-old man diagnosed with extensive hepatic AE requiring ex-situ extended right-sided liver resection including the caudate lobe and retro-hepatic vena cava. The left liver segments were auto-transplanted with reconstruction of the left hepatic vein and an inferior vena cava graft. In the post-operative course, the patient developed a bile leak, which was successfully managed with endoscopic stent intervention. He was discharged after a three-week hospitalization. Medical treatment with albendazole was initiated preoperatively and continued postoperatively. [ABSTRACT FROM AUTHOR]

Background: Identification of patients at high risk of surgical-site infections may allow surgeons to minimize associated morbidity. However, there are significant concerns regarding the methodological quality and transportability of models previously developed. The aim of this study was to develop a novel score to predict 30-day surgical-site infection risk after gastrointestinal surgery across a global context and externally validate against existing models. Methods: This was a secondary analysis of two prospective international cohort studies: GlobalSurg-1 (July–November 2014) and GlobalSurg-2 (January–July 2016). Consecutive adults undergoing gastrointestinal surgery were eligible. Model development was performed using GlobalSurg-2 data, with novel and previous scores externally validated using GlobalSurg-1 data. The primary outcome was 30-day surgical-site infections, with two predictive techniques explored: penalized regression (least absolute shrinkage and selection operator ('LASSO')) and machine learning (extreme gradient boosting ('XGBoost')). Final model selection was based on prognostic accuracy and clinical utility. Results: There were 14 019 patients (surgical-site infections = 12.3%) for derivation and 8464 patients (surgical-site infections = 11.4%) for external validation. The LASSO model was selected due to similar discrimination to extreme gradient boosting (AUC 0.738 (95% c.i. 0.725 to 0.750) versus 0.737 (95% c.i. 0.709 to 0.765)), but greater explainability. The final score included six variables: country income, ASA grade, diabetes, and operative contamination, approach, and duration. Model performance remained good on external validation (AUC 0.730 (95% c.i. 0.715 to 0.744); calibration intercept −0.098 and slope 1.008) and demonstrated superior performance to the external validation of all previous models. Conclusion: The 'Global Surgical-Site Infection' score allows accurate prediction of the risk of surgical-site infections with six simple variables that are routinely available at the time of surgery across global settings. This can inform the use of intraoperative and postoperative interventions to modify the risk of surgical-site infections and minimize associated harm. There are significant concerns regarding the methodological quality and transportability of models previously developed to predict patients at risk of surgical-site infections to allow surgeons to minimize associated morbidity. The novel 'Global Surgical-Site Infection' score allows accurate prediction of the risk of surgical-site infections with six simple variables that are routinely available at the time of surgery across global settings. This can inform the use of intraoperative and postoperative interventions to modify the risk of surgical-site infections and minimize associated harm. Lay Summary: This study is about finding ways to predict if someone will get an infection after having surgery on their stomach and intestines. If doctors know who is at high risk of getting an infection, they can take steps to prevent it and help the patient recover faster. The researchers used information from patients who had surgery all over the world to try to make a way to score how likely someone is to get infection in their wound from surgery. They did this in two different ways, then picked the one that was best at picking up infections, while still being easy to use. They then compared the new score against older scores to check if it really was better or not. The researchers found that their new score was good at predicting who might get an infection using just six bits of information on the patient. This new score worked even better than older scores when these were compared all together. This means that doctors can use this new score to check who is most likely to get an infection after surgery and so can take extra steps during and after the surgery to try and stop these from happening. Because the score is so simple, this is easy to use all around the world. [ABSTRACT FROM AUTHOR]

Introduction FebriDx® is a CE-marked, single-use point-of-care test with markers for bacterial [C-reactive protein (CRP)] and viral [myxovirus resistance protein A (MxA)] infection, using finger-prick blood samples. Results are available after 10–12 min. We explored the usability and potential impact of FebriDx® in reducing antibiotic prescriptions for lower respiratory tract infection (LRTI) in primary care, and the feasibility of conducting a randomized controlled trial (RCT). Methods Patients (aged ≥1 year) with LRTI deemed likely to receive antibiotic prescription were recruited at nine general practices and underwent FebriDx® testing. Data collection included FebriDx® results, antibiotic prescribing plan (before and after testing) and re-consultation rates. Staff completed System Usability Scale questionnaires. Results From 31 January 2023 to 9 June 2023, 162 participants participated (median age 57 years), with a median symptom duration of 7 days (IQR 5–14). A valid FebriDx® result was obtained in 97% (157/162). Of 155 patients with available results, 103 (66%) had no detectable CRP or MxA, 28 (18%) had CRP only, 5 (3%) had MxA only, and 19 (12%) had both CRP and MxA. The clinicians' stated management plan was to prescribe antibiotics for 86% (134/155) before testing and 45% (69/155) after testing, meaning a 41% (95% CI: 31%, 51%) difference after testing, without evidence of increased re-consultation rates. Ease-of-use questionnaires showed 'good' user-friendliness. Conclusions Use of FebriDx® to guide antibiotic prescribing for LRTI in primary care was associated with a substantial reduction in prescribing intentions. These results support a fully powered RCT to confirm its impact and safety. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has highlighted the need to use infection testing databases to rapidly estimate effectiveness of prior infection in preventing reinfection (⁠|$P{E}_S$|⁠) by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Mathematical modeling was used to demonstrate a theoretical foundation for applicability of the test-negative, case–control study design to derive |$P{E}_S$|⁠. Apart from the very early phase of an epidemic, the difference between the test-negative estimate for |$P{E}_S$| and true value of |$P{E}_S$| was minimal and became negligible as the epidemic progressed. The test-negative design provided robust estimation of |$P{E}_S$| and its waning. Assuming that only 25% of prior infections are documented, misclassification of prior infection status underestimated |$P{E}_S$|⁠ , but the underestimate was considerable only when > 50% of the population was ever infected. Misclassification of latent infection, misclassification of current active infection, and scale-up of vaccination all resulted in negligible bias in estimated |$P{E}_S$|⁠. The test-negative design was applied to national-level testing data in Qatar to estimate |$P{E}_S$| for SARS-CoV-2. |$P{E}_S$| against SARS-CoV-2 Alpha and Beta variants was estimated at 97.0% (95% CI, 93.6-98.6) and 85.5% (95% CI, 82.4-88.1), respectively. These estimates were validated using a cohort study design. The test-negative design offers a feasible, robust method to estimate protection from prior infection in preventing reinfection. [ABSTRACT FROM AUTHOR]

Background Antimicrobial peptides (AMPs) are key effectors of urinary tract innate immunity. Identifying differences in urinary AMP levels between younger and older adults is important in understanding older adults' susceptibility and response to urinary tract infections (UTI) and AMP use as diagnostic biomarkers. We hypothesized that uninfected older adults have higher urinary human neutrophil peptides 1-3 (HNP 1-3), human alpha-defensin-5 (HD-5), and human beta-defensin-2 (hBD-2), but lower urinary cathelicidin (LL-37) than younger adults. Methods We conducted a cross-sectional study of patients aged ≥18 years completing a family medicine clinic nonacute visit. Enzyme-linked immunosorbent assays were performed for AMPs. We identified associations between age and AMPs using unadjusted and multivariable linear regression models. Results Of the 308 subjects, 144 (46.8%) were ≥65 years of age. Comparing age ≥65 versus < 65 years, there were no significant differences in HNP 1-3 (p  = .371), HD5 (p  = .834), or LL-37 (p  = .348) levels. Values for hBD-2 were lower in older adults versus younger (p  < .001). In multivariable analyses, older males and females had significantly lower hBD-2 levels (p  < .001 and p  = .004). Models also showed urine leukocyte esterase was associated with increased levels of HNP 1-3 and HD5; hematuria with increased hBD-2; and urine cultures with contamination with increased HNP 1-3 and hBD-2. Conclusions Baseline urinary HNP 1-3, HD-5, and LL-37 did not vary with age. Older adults had lower baseline hBD-2. This finding has implications for the potential use of urinary AMPs as diagnostic markers and will facilitate further investigation into the role of innate immunity in UTI susceptibility in older adults. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV)-associated malignancies account for ~5% of human cancers worldwide. Thirteen, or more, HPV types are oncogenic, but infection with these viruses is common and usually cleared within 2 years. Only infections that become persistent are associated with the development of cancer, often occurring several decades later. These cancers mostly arise in 6 different anatomical regions: 5 are anogenital (anus, cervix, penis, vagina, and vulva) and the sixth is the oropharynx. Oncogenic HPVs promote cellular proliferation and genomic instability, but the anatomical niche of the target tissue also plays an important role in the development of cancer. Cells that reside in transitional regions between different types of epithelia, such as in the anus, cervix, and oropharynx, are particularly vulnerable to oncogenesis. [ABSTRACT FROM AUTHOR]

Background The 2030 target for schistosomiasis is elimination as a public health problem (EPHP), achieved when the prevalence of heavy-intensity infection among school-aged children (SAC) reduces to <1%. To achieve this, the new World Health Organization guidelines recommend a broader target of population to include pre-SAC and adults. However, the probability of achieving EPHP should be expected to depend on patterns in repeated uptake of mass drug administration by individuals. Methods We employed 2 individual-based stochastic models to evaluate the impact of school-based and community-wide treatment and calculated the number of rounds required to achieve EPHP for Schistosoma mansoni by considering various levels of the population never treated (NT). We also considered 2 age-intensity profiles, corresponding to a low and high burden of infection in adults. Results The number of rounds needed to achieve this target depends on the baseline prevalence and the coverage used. For low- and moderate-transmission areas, EPHP can be achieved within 7 years if NT ≤10% and NT <5%, respectively. In high-transmission areas, community-wide treatment with NT <1% is required to achieve EPHP. Conclusions The higher the intensity of transmission, and the lower the treatment coverage, the lower the acceptable value of NT becomes. Using more efficacious treatment regimens would permit NT values to be marginally higher. A balance between target treatment coverage and NT values may be an adequate treatment strategy depending on the epidemiological setting, but striving to increase coverage and/or minimize NT can shorten program duration. [ABSTRACT FROM AUTHOR]

Fever of unknown origin (FUO) is a clinical conundrum for patients and clinicians alike, and imaging studies are often performed as part of the diagnostic workup of these patients. Recently, the Society of Nuclear Medicine and Molecular Imaging convened and approved a guideline on the use of nuclear medicine tools for FUO. The guidelines support the use of 2-18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in adults and children with FUO. 18F-FDG PET/CT allows detection and localization of foci of hypermetabolic lesions with high sensitivity because of the 18F-FDG uptake in glycolytically active cells that may represent inflammation, infection, or neoplasia. Clinicians should consider and insurers should cover 18F-FDG PET/CT when evaluating patients with FUO, particularly when other clinical clues and preliminary studies are unrevealing. [ABSTRACT FROM AUTHOR]