Search

Targeted protein degradation has been widely adopted as a new approach to eliminate both established and previously recalcitrant therapeutic targets. Here, it is reported that the development of small molecule degraders of the envelope (E) protein of dengue virus. Two classes of bivalent E‐degraders are developed by linking two previously reported E‐binding small molecules, GNF‐2, and CVM‐2‐12‐2, to a glutarimide‐based recruiter of the CRL4CRBN ligase to effect proteosome‐mediated degradation of the E protein. ZXH‐2‐107 (based on GNF‐2) is an E‐degrader with ABL inhibitory activity while ZXH‐8‐004 (based on CVM‐2‐12‐2) is a selective and potent E‐degrader. These two compounds provide proof of concept that difficult‐to‐drug targets such as a viral envelope protein can be effectively eliminated using a bivalent degrader and provide starting points for the future development of a new class of direct‐acting antiviral drugs. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusions Concerns exist that intravenous (IV) iron might increase the risk of infections. The IRONMAN trial provided an opportunity to investigate whether giving IV ferric derisomaltose (FDI) to patients with heart failure and iron deficiency alters the rate of hospitalization or death due to infections.IRONMAN was a randomized trial of IV FDI versus usual care in patients with symptomatic heart failure, left ventricular ejection fraction (LVEF) ≤45%, and transferrin saturation (TSAT) <20% or ferritin <100 μg/L. Infection was a pre‐specified, blindly‐adjudicated, safety endpoint. The primary analysis of interest was infection as the main reason for hospitalization or death, using first and recurrent events analyses. The composite primary event of interest tended to be lower in those randomized to FDI when analysed as first (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.62–1.01, p = 0.055) or recurrent event (rate ratio 0.85, 95% CI 0.64–1.13, p = 0.089). The composite results were driven by fewer hospitalizations for infection (HR 0.76, 95% CI 0.49–0.98, p = 0.032), with 5% fewer patients (absolute reduction) experiencing such an event if assigned to FDI. Similar trends were observed for recurrent events (HR 0.82, 95% CI 0.62–1.10). Further analyses suggested that the reduction in hospitalizations due to infection with FDI was restricted to patients with TSAT <20%.In patients with heart failure and a reduced LVEF, correction of iron deficiency is not associated with an increased risk of hospitalization or death from infection, and may reduce such events, especially when TSAT is <20%.Clinical Trial Registration: ClinicalTrials.gov, NCT02642562. [ABSTRACT FROM AUTHOR]

Malaria is a mosquito‐borne disease caused by Plasmodium parasites, responsible for a significant impact on public health in several tropical and sub‐tropical countries. The majority of infection cases are classified as uncomplicated malaria, causing mild symptoms such as fever and headache. However, the disease may progress to severe malaria and death if the infection is not properly treated. Furthermore, malaria poses a major concern for children, pregnant women and immunosuppressed individuals. Exacerbated inflammation is characteristic of severe malaria cases. The C–C chemokine receptor type 5 (CCR5) is an important molecule for leukocyte migration and regulation of inflammation. Although widely known as an HIV‐1 co‐receptor, CCR5 also affects the susceptibility and progression of autoimmune and inflammatory diseases. There is evidence supporting the participation of CCR5 in malaria manifestations, with the evaluation of CCR5 gene expression levels suggested as a marker to monitor malaria severity. Certain genetic variants in the CCR5 gene affect CCR5 expression, potentially altering CCR5‐mediated inflammatory responses during malaria infection. However, the complex influences of CCR5 on malaria remain underexplored. Therefore, this review examines and updates the role of CCR5 in various contexts of malaria infection, including uncomplicated malaria, Plasmodium/HIV co‐infection, pregnancy and severe (cerebral) malaria. [ABSTRACT FROM AUTHOR]

Objective Materials and Methods Results Conclusion To evaluate the relationship between renal pelvis pressure and infection after ureteroscopy, using a live swine model.In anaesthetised pigs, a 1‐h ureteroscopy was performed using a pressure‐sensing guidewire, with renal pelvis pressure maintained at either 37 mmHg or 75 mmHg for the entire procedure and infusion with saline alone or with a standardised concentration of uropathogenic Escherichia coli strain CFT073 (1.5 × 107 colony‐forming units [CFU]/mL). Venous blood sampling was performed during and after the procedure. Vital signs, inflammatory biomarkers, and renal tissue and blood cultures were assessed.In 21 pig kidneys, study groups were: 37 mmHg with saline irrigation (n = 3); 75 mmHg with saline irrigation (n = 4); 37 mmHg with saline irrigation with 1.5 × 107 CFU/mL E. coli (n = 7); and 75 mmHg with saline irrigation with 1.5 × 107 CFU/mL E. coli (n = 7). Statistically significant changes in inflammatory biomarkers were most pronounced in the group with 75 mmHg saline irrigation + E. coli and were significantly elevated compared with the control group and the group receiving E. coli irrigation at 37 mmHg. Positive blood cultures were noted in 5/7 animals treated with E. coli at 75 mmHg; no others developed bacteraemia.In this swine model of ureteroscopy, irrigation with saline + E. coli at a renal pelvis pressure of 75 mmHg resulted in bacteraemia and inflammatory biomarker elevations significantly greater than both E. coli irrigation with renal pelvis pressure maintained at 37 mmHg and the control. [ABSTRACT FROM AUTHOR]

In the current era, environmental factors are well established as major causative agents for all cancers especially lung and breast cancer. We sought to review the current available literature on the topic pertaining to gynaecologic cancers. Although a few factors are well established in literature, others need more research to conclude. [ABSTRACT FROM AUTHOR]

Venous leg ulcers (VLUs) represent one of the most prevalent types of chronic wounds characterised by perturbed microbiome and biofilm‐forming bacteria. As one of the most abundant skin‐commensal, Staphylococcus epidermidis is known as beneficial for the host, however, some strains can form biofilms and hinder wound healing. In this study, S. epidermidis distribution in VLUs and associated resistome were analysed in ulcer tissue from patients. Virulence of S. epidermidis isolates from VLUs were evaluated by whole genome sequencing, antimicrobial susceptibility testing, in vitro biofilm and binding assays, and assessment of biofilm‐forming capability and pro‐inflammatory potential using human ex vivo wound model. We demonstrated that S. epidermidis isolates from VLUs inhibit re‐epithelialization through biofilm‐dependent induction of IL‐1β, IL‐8, and IL‐6 which was in accordance with impaired healing outcomes observed in patients. High extracellular matrix binding ability of VLU isolates was associated with antimicrobial resistance and expression levels of the embp and sdrG, responsible for bacterial binding to fibrinogen and fibrin, respectively. Finally, we showed that S. epidermidis from VLUs demonstrate pathogenic features with ability to impair healing which underscores the emergence of treatment‐resistant virulent lineages in patients with chronic ulcers. [ABSTRACT FROM AUTHOR]

Plain language summary Cytomegalovirus (CMV) is the most common cause of viral infection in newborn babies, and affects 1 in 200 of all live born infants in high‐income countries; and 1 in 71 in low‐ and middle‐income countries. It is a major cause of hearing loss and brain damage.Women may get CMV infection for the first time during pregnancy (primary infection) or may experience ‘non‐primary’ infection, either by reactivation of previous CMV infection or by a new infection with a different strain of the virus. The most common source of infection to pregnant women is the saliva and urine of young children. Therefore, all pregnant women, especially those in regular contact with young children, should be informed about hygiene‐based measures to reduce the risks, e.g. handwashing.The UK National Screening Committee recommends against universal antenatal or newborn screening for CMV. Testing for CMV is usually offered only to women who develop symptoms of influenza, glandular fever or hepatitis (liver inflammation) during pregnancy, or for those whom a routine ultrasound scan detects fetal anomalies that suggests possible CMV infection.The risk of harm to the fetus is greatest following primary CMV infection of the woman in early pregnancy, and appears to be very low following infection after 12 weeks of pregnancy. Babies with CMV infection at birth may have jaundice, a rash, enlarged liver or spleen, a small brain, or be small for their gestational age. Around 1 in 8 babies born with CMV infection will have clinically detectable signs at birth. The rest will not have any features detectable by clinical examination alone. Therefore, all infants with CMV infection at birth should be followed up at a minimum of up to 2 years of age or later, depending upon the disease status, to check hearing and brain development.Following primary CMV infection in the first 12 weeks of pregnancy, if the woman starts taking the antiviral medicine valaciclovir (valacyclovir) it reduces the risk of the baby becoming infected.Where CMV infection of the fetus in the womb has been confirmed (by amniocentesis, for example), regular ultrasound scans should be offered every 2–3 weeks until birth. Detailed assessment of the fetal brain is an essential part of these scans. Where maternal CMV infection occurs, but fetal infection is not confirmed, repeated ultrasound scans of the fetus should be offered every 2–3 weeks until birth.In infected fetuses, as well as ultrasound scans, an MRI scan of the brain should be offered at 28–32 weeks of gestation (and sometimes repeated 3–4 weeks later) to assess for any signs of harm to the fetal brain.All babies born to women with confirmed or suspected CMV infection should be tested for CMV with a urine or saliva sample within the first 21 days of life.In newborns with symptomatic CMV infection at birth, treatment with antiviral medicine (valganciclovir or ganciclovir) can reduce hearing loss in 5 out of 6 babies, and improve long‐term brain development outcomes in some. There is no licensed vaccine for CMV. [ABSTRACT FROM AUTHOR]

Host‐specific pathogens have long been suggested to act as a major driver of species diversity in tropical forests. However, determining the degree of host specificity of potential pathogens coupled to key cellular characteristics of infection is difficult and time‐consuming. These challenges have delayed progress in relating the functional specificity of pathogenic fungi to ecological consequences. We tested the pathogenicity of 27 (of 215) fungi that were isolated from surface sterilized roots of seedlings from four common tree species in a diverse subtropical forest. Inoculation experiments showed that six fungi exhibited strong pathogenicity on the host seedlings. Five of these only infected their specific hosts (i.e. host‐specific pathogen species). Green fluorescent protein labelling revealed that in three host‐specific pathogens fungal hyphae were able to grow into the vascular tissues only in their specific host plant, in contrast to other fungal‐host combinations that exhibit non‐pathogenic interactions. This fluorescent labelling technique allows direct tracking of the progress of fungal infection in different host tissues. Synthesis. By coupling the green fluorescent protein technique with standard host inoculation experiments, we determined the developmental differences between infections by pathogenic and non‐pathogenic fungi in a relatively simple and straightforward way. Our work provides a useful tool for rapidly screening and categorizing host–fungal interactions, reflecting the functional basis of host specificity of pathogenic fungi. More broadly, this technique can contribute to understanding the roles of pathogens in species coexistence and biodiversity maintenance in forest communities. [ABSTRACT FROM AUTHOR]

Summary This manuscript sheds light on the impact of maternal breast milk antibodies on infant health. Milk antibodies prepare and protect the newborn against environmental exposure, guide and regulate the offspring's immune system, and promote transgenerational adaptation of the immune system to its environment. While the transfer of IgG across the placenta ceases at birth, milk antibodies are continuously replenished by the maternal immune system. They reflect the mother's real‐time adaptation to the environment to which the infant is exposed. They cover the infant's upper respiratory and digestive mucosa and are perfectly positioned to control responses to environmental antigens and might also reach their circulation. Maternal antibodies in breast milk play a key role in the immune defense of the developing child, with a major impact on infectious disease susceptibility in both HIC and LMIC. They also influence the development of another major health burden in children—allergies. Finally, emerging evidence shows that milk antibodies also actively shape immune development. Much of this is likely to be mediated by their effect on the seeding, composition and function of the microbiota, but not only. Further understanding of the bridge that maternal antibodies provide between the child and its environment should enable the best interventions to promote healthy development. [ABSTRACT FROM AUTHOR]

Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous adverse reactions to medications characterized by keratinocyte necrosis leading to loss of protective barrier function and increased susceptibility to infection. Infection is a major cause of morbidity, and septicemia is the leading cause of mortality in this population. This systematic review and meta‐analysis aimed to determine infectious complications' prevalence and risk factors in adults with SJS and TEN. This review was registered with the International Platform of Registered Systematic Review and Meta‐Analysis Protocols (INPLASY) and conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) reporting guidelines. Thirty‐six articles describing results from 1446 cases were included. Skin infection was the most commonly diagnosed infection. The pooled prevalence of sepsis, respiratory tract infection, skin infection, and urinary tract infection was 27.3%, 21.5%, 37.5%, and 21.8%, respectively. Staphylococcus aureus was the most commonly identified organism. The overall quality of the studies was suboptimal, and the level of heterogeneity was high. The skin, bloodstream, respiratory, and urinary tracts are most commonly infected in the course of adult SJS and TEN. During hospitalization, clinicians should closely monitor and promptly investigate for these as well as several other infectious complications. More research is needed, with greater attention to the risk factors and causative organisms that cause these infections. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and Aims Methods Results Conclusions Metabolic dysfunction‐associated steatotic liver disease (MASLD) is linked to various intrahepatic and extrahepatic diseases, but its association with severe infectious disease remains to be investigated.We analysed data from the Shanghai Suburban Adult Cohort and Biobank, encompassing participants enrolled in 2016 and 2017 with available abdominal ultrasonography data, and followed them up until December 2022 (median follow‐up = 5.71 years). We categorised the participants into the MASLD group and those without steatotic liver disease (non‐SLD). Multivariable‐adjusted Cox regression was used to estimate hazard ratios (HR) for severe infections in patients with MASLD compared to the non‐SLD group. Cumulative incidences were calculated while accounting for competing risks (non‐infection‐related deaths). Mediation analyses were performed to explore the roles of cardiometabolic risk factors in the association between MASLD and severe infections.Among the 33 072 eligible participants (mean age 56.37 years; 38.20% male), 11 908 (36.01%) were diagnosed with MASLD at baseline. Severe infections occurred in 912 (7.66%) MASLD patients and 1258 (5.94%) non‐SLD. The rate of severe infections per 1000 person‐years was higher in MASLD patients (13.58) than in comparators (10.48) (fully adjusted HR 1.18, 95% CI 1.07–1.30). The most frequent infections in MASLD were respiratory (7.25/1000 person‐years) and urinary tract infections (2.61/1000 person‐years). The 5‐year cumulative incidence of severe infections was 6.79% (95% CI 6.36–7.26) in MASLD and 5.08% (95% CI 4.79–5.38) in comparators. Cardiometabolic risk factors, including waist circumference, triglycerides and HbA1C, partially mediate the association between MASLD and severe infections.Patients with MASLD were at significantly higher risk of incident severe infections compared to the non‐SLD group. Future studies are needed to elucidate the mechanisms linking MASLD to severe infections. [ABSTRACT FROM AUTHOR]

The arboviral disease dengue is a life-threatening global public health problem due to its high prevalence rate, morbidity and mortality. Recent studies suggest that morbidity during secondary dengue infection is higher than during primary infection. To deepen our understanding, we have explored a two-serotype co-infected dengue model with bilinear incidence for primary infection and saturated incidence for secondary infection. In the model, we have also included four control measures: mosquito bite prevention control, treatment control, vaccine control and mosquito killing control. The existence and local stability of the disease free, serotype II free, serotype I free and endemic equilibrium points have been studied. The effect of inhibitory or awareness factors on disease dynamics has also been exhaustively examined. By using sensitivity analysis we have identified and quantified the most influential parameters to prevent as well as to control the dengue outbreak. To optimize our strategies, we have characterized the time-dependent optimal control to reduce dengue prevalence and the total implementation cost of the aforementioned controls. Efficiency analysis has been done to identify the best effective combination of the applied controls to reduce dengue infection. Mosquito bites with treatment control is the most effective combined strategy to control dengue infection. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Design Setting Population or Sample Methods Main Outcome Measures Results Conclusions Adverse birth outcomes and the maternal severity of influenza in pregnancy are well documented but information on pertussis is limited.Population‐based linkage data were collected during 2001–2016.New South Wales, Australia.A total of 1 453 037 singleton births.Cox regression was used to estimate the associations between pertussis or influenza during pregnancy and birth outcomes with adjustment of covariates.Adverse birth outcomes (preterm birth and low birth weight).Among 1 453 037 singleton births over 16 years, we identified pertussis in 925 (49; 5.3% hospitalised) and influenza in 2850 (1092; 38.3% hospitalised) women during pregnancy. Cases of pertussis were similarly distributed by trimester (32% 3rd) whereas 46% of influenza cases were in the 3rd trimester. Younger age, previous birth, and being overseas‐born were associated with both pertussis and influenza, whereas identifying as Aboriginal or Torres Strait Islander, hypertension or diabetes before and during pregnancy, and a number of other factors were only associated with influenza. Both pertussis and influenza in pregnancy were associated with increased risk of preterm birth (pertussis: aHR = 1.30, 95% CI 1.01–1.68; influenza: aHR = 1.56, 95% CI 1.36–1.79) and these increased risks were greater when infections in the period within 2 weeks of birth were considered (pertussis: aHR = 2.36, 95% CI 1.26–4.41; influenza: aHR = 2.29, 95% CI 1.78–2.96).Maternal pertussis and influenza infections close to the time of birth were associated with adverse birth outcomes. These findings highlight the benefits of vaccination during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis and bone fractures affect health and quality of life. Since bone disease is multifactorial, identifying risk factors is key in prevention. There are multiple reports on how viral hepatitis, especially chronic hepatitis B (CHB) and chronic hepatitis C (CHC), are affecting bone disease, but results vary. Here, we analyzed the potential association between CHB/CHC and osteoporosis or bone fractures in a large outpatient cohort in Germany. Methods: We included 3136 outpatients with CHB and 15,608 matched non-hepatitis individuals as well as 2867 outpatients with CHC and 14,335 matched non-hepatitis individuals from the Disease Analyzer Database between 2005 and 2022. The main outcome was the 5-year cumulative incidence of osteoporosis and bone fractures as a function of either CHB or CHC. Results: Within 5 years of the index date, 2.9% vs. 1.6% of patients with and without CHB were diagnosed with osteoporosis (p = 0.001) and 1.0% vs. 0.4% were diagnosed with bone fractures (p < 0.001). Moreover, 3.3% of CHC patients and 2.2% of individuals without hepatitis C were diagnosed with osteoporosis (p = 0.002). In Cox regression analyses, CHB was significantly associated with an increased risk for osteoporosis (HR: 1.76) and fractures (HR:2.43) and CHC with osteoporosis (HR: 1.54). For both CHB and CHC, the association with osteoporosis was restricted to the female subgroup. Conclusions: CHB and CHC are associated with osteoporosis in women. CHB in male patients is associated with a higher risk of fractures. More research is needed to understand the underlying pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

Adrenomedullin has emerged as a promising biomarker in the field of viral diseases. Numerous studies have demonstrated its potential in assessing disease severity, predicting clinical outcomes, and monitoring treatment response. Adrenomedullin (AM) is a multifaceted peptide implicated in vasodilation, hormone secretion, antimicrobial defense, cellular growth, angiogenesis, and, importantly, chronic pain. AM and related peptides interface with cytoskeletal proteins within neuronal contexts, influencing microtubule dynamics. AM has primarily been utilized in diagnosing diseases of bacterial origin, including sepsis. Nevertheless, there are reports suggesting its utility in diseases of viral origin, and this is the focus of the present study. Furthermore, adrenomedullin has been shown to be elevated in various viral infections, suggesting its role in immune response modulation. Furthermore, AM may contribute to neuronal dysfunction through mechanisms involving immune and inflammatory responses, apoptosis, and disruptions in calcium homeostasis. This review aims to consolidate current knowledge regarding AM and its potential implications in viral diseases, elucidating its diverse roles in neurological pathophysiology. This review highlights the growing importance of adrenomedullin as a biomarker in viral diseases and the need for further functional studies to understand the underlying mechanisms involved. [ABSTRACT FROM AUTHOR]

The plant vascular system is not only a transportation system for delivering nutrients but also a highway transport network for spreading viruses. Tomato spotted wilt orthotospovirus (TSWV) is among the most destructive viruses that cause serious losses in economically important crops worldwide. However, there is minimal information about the long-distance movements of TSWV in the host plant vascular system. In this this study, we confirm that TSWV virions are present in the xylem as observed by transmission electron microscopy (TEM). Further, a quantitative proteomic analysis based on label-free methods was conducted to reveal the uniqueness of protein expression in xylem sap during TSWV infection. Thus, this study identified and quantified 3305 proteins in two groups. Furthermore, TSWV infection induced three viral structural proteins, N, Gn and Gc, and 315 host proteins differentially expressed in xylem (163 up-regulated and 152 down-regulated). GO enrichment analysis showed up-regulated proteins significantly enriched in homeostasis, wounding, defense response, and DNA integration terms, while down-regulated proteins significantly enriched in cell wall biogenesis/xyloglucan metabolic process-related terms. KEGG enrichment analysis showed that the differentially expressed proteins (DEPs) were most strongly associated with plant-pathogen interaction, MAPK signaling pathway, and plant hormone signal transduction. Cluster analysis of DEPs function showed the DEPs can be categorized into cell wall metabolism-related proteins, antioxidant proteins, PCD-related proteins, host defense proteins such as receptor-like kinases (RLKs), salicylic acid binding protein (SABP), pathogenesis related proteins (PR), DNA methylation, and proteinase inhibitor (PI). Finally, parallel reaction monitoring (PRM) validated 20 DEPs, demonstrating that the protein abundances were consistent between label-free and PRM data. Finally, 11 genes were selected for RT-qPCR validation of the DEPs and label-free-based proteomic analysis concordant results. Our results contribute to existing knowledge on the complexity of host plant xylem system response to virus infection and provide a basis for further study of the mechanism underlying TSWV long-distance movement in host plant vascular system. [ABSTRACT FROM AUTHOR]

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]

Introduction: Cancer, malnutrition, and surgery negatively impact patient's immune system. Despite standardized surgical technique and the development of new perioperative care protocols, morbidity after cystectomy remains a serious challenge for urologists. Most common postoperative complications, such as infections and ileus, often lead to longer length of stay and worse survival. The immune system and its interaction with the gut microbiota play a pivotal role in cancer immunosurveillance and in patient's response to surgical stress. Malnutrition has been identified as an independent and modifiable risk factor for both mortality and morbidity. Immunonutrition (IN) may improve the nutritional status, immunological function, and clinical outcome of surgical patients. Aims of the study are (1) to evaluate the impact of IN on morbidity and mortality at 30 and 90 days after cystectomy and (2) to determine immune and microbiota signature that would predict IN effect. Methods: This is a randomized, multicentric, controlled, pragmatic, parallel-group comparative study, supported by the Swiss National Science Foundation. A total of 232 patients is planned to be enrolled between April 2023 and June 2026. Three participating centers (Lausanne, Bern, and Riviera-Chablais) have been selected. All patients undergoing elective radical and simple cystectomy will be randomly assigned to receive 7 days of preoperative IN (Oral Impact®, Nestlé, Switzerland) versus standard of care (control group) and followed for 90 days after surgery. For the exploratory outcomes, blood, serum, urine, and stool samples will be collected in patients treated at Lausanne. In order to determine the impact of IN on immune fitness, patients enrolled at Lausanne will be vaccinated against influenza and the establishment of the vaccine-specific immune response will be followed. Analysis of the microbiota and expression of argininosuccinate synthetase 1 as potential biomarker will also be performed. Discussion and conclusion: Strengths of the INCyst study include the randomized, multicenter, prospective design, the large number of patients studied, and the translational investigation. This study will challenge the added value of preoperative IN in patients undergoing cystectomy, assessing the clinical effect of IN on the onset of postoperative morbidity and mortality after cystectomy. Furthermore, it will provide invaluable data on the host immune response and microbiota composition. Trial registration: ClinicalTrials.gov NCT05726786. Registered on March 9, 2023. [ABSTRACT FROM AUTHOR]

BACKGROUND. Most humans have been infected with cytomegalovirus (CMV) by midlife without clinical signs of disease. However, in settings in which the immune system is undeveloped or compromised, the virus is not adequately controlled and consequently presents a major infectious cause of both congenital disease during pregnancy as well as opportunistic infection in children and adults. With clear evidence that risk to the fetus varies with gestational age at the time of primary maternal infection, further research on humoral responses to primary CMV infection during pregnancy is needed. METHODS. Here, systems serology tools were applied to characterize antibody responses to CMV infection in pregnant and nonpregnant women experiencing either primary or chronic infection. RESULTS. Whereas strikingly different antibody profiles were observed depending on infection status, limited differences were associated with pregnancy status. Beyond known differences in IgM responses used clinically for identification of primary infection, distinctions observed in IgA and FcγR-binding antibodies and among antigen specificities accurately predicted infection status. Machine learning was used to define the transition from primary to chronic states and predict time since infection with high accuracy. Humoral responses diverged over time in an antigen-specific manner, with IgG3 responses toward tegument decreasing over time as typical of viral infections, while those directed to pentamer and glycoprotein B were lower during acute and greatest during chronic infection. CONCLUSION. In sum, this work provides insights into the antibody response associated with CMV infection status in the context of pregnancy, revealing aspects of humoral immunity that have the potential to improve CMV diagnostics. FUNDING. CYMAF consortium and NIH NIAID. [ABSTRACT FROM AUTHOR]

Our previous study first reported the efficacy of FURL using 365 μm fibers with holmium: yttrium aluminum garnet (Ho: YAG) laser lithotripsy. This study evaluates the 16-week safety of this procedure. A prospective cohort study was conducted, and the clinical characteristics of patients who underwent FURL using 365 μm fibers with Ho: YAG laser were retrospectively collected. Descriptive statistics were reported, and logistic regression analysis was conducted to identify risk factors influencing the stone-free rate (SFR). Infection-related laboratory parameters, including white blood cell count (WBC), procalcitonin (PCT), and C-reactive protein (CRP), were collected. Regression analysis was conducted to identify risk factors for the development of urosepsis post-surgery. Additionally, a 16-week follow-up was conducted in outpatient clinics, and kidney function was assessed. A total of 274 patients participated in this study. The 4-week stone-free rate (SFR) following FURL with 365 μm fibers of Ho: YAG laser was significantly associated with stone size and composition. No severe complications were observed following FURL procedures. There were no significant differences in white blood cell count (WBC), C-reactive protein (CRP), and procalcitonin (PCT) in peripheral blood before and after FURL procedures. Urosepsis was diagnosed in 1.82% of patients. Preoperative white blood cell count (WBC) in urine and preoperative urine culture results were identified as significant risk factors. Kidney function remained stable at 4 and 16 weeks following FURL. This prospective cohort study demonstrated the high safety of FURL with 365 μm fibers of Ho: YAG laser, as infection-related parameters during the perioperative period showed no significant differences, and kidney function remained stable throughout the 16-week follow-up. [ABSTRACT FROM AUTHOR]

Background: In COVID-19 management, a variety of pharmaceutical interventions (PI) and non- pharmaceutical interventions (NPI) were adopted to limit the spread of the disease and its associated deaths. We aimed to evaluate the impact of PI and NPI on risks of COVID-19 transmission and deaths. Method: We collected aggregate data from March 2nd, 2020, to December 1, 2022 from the Tunisian Ministry of Health's website and OurWorldInData.org site. NPI Periods (NPIP: March 2020 to March 2021) and PI Periods (PIP) were distributed to NPIP1, 2, 3 and 4 and to PIP1, 2, 3 and 4, respectively. We calculated the Relative Risks (RR) and 95% Confidence Intervals (CI) by comparing the subsequent period with previous one. Results: The risk of SARS-CoV-2 transmission increased progressively from the zero cases period (NPIP2) to the mitigate strategy period (NPIP3) (RR = 14.0; 95% CI: 12.4–15.8) and to the stop-and-go epidemic control period (NPIP4) (RR = 23.1 (95% CI: 22.4–23.9). It was stabilized in the targeted vaccination period (PIP1) (RR = 1.08, 95% CI: 1.07–1.08) and reduced during the mass vaccination period (PIP2) (RR: 0.50, 95% CI: 0.50–0.51). SARS-CoV-2 transmission, increased during PIP3 concomitant with the Omicron wave (RR = 2.65, 95% CI: 2.64–2.67). It remained at a low level in PIP4 (RR = 0.18; 95% CI: 0.18–0.18). Compared to NPIP2, NPIP3 and NPIP4 were associated with a higher risk of COVID-19 mortality (RR = 3.337; 95% CI: 1.797–6.195) and (RR = 72.63 (95% CI: 54.01–97.68), respectively. Since the start of the immunization program, the risk of COVID-19 death has consistently decreased. In comparison to each previous period, the risk transitioned in PIP1 to RR = 0.91; 95% CI: 0.88–0.93, then to RR = 0.85; 95% CI: 0.83–0.88 in PIP2, to RR = 0.47; 95% CI: 0.45–0.50 in PIP3, and to RR = 0.19; 95% CI: 0.18–0.24 during PIP4. Conclusion: In terms of lowering the risk of transmission and mortality, the NP strategy at the beginning of the epidemic outperformed the IP strategy during the outbreak. [ABSTRACT FROM AUTHOR]

Chronic active Epstein-Barr virus infection (CAEBV) is a progressive and life-threatening disease characterized by persistent or recurrent EBV activation. It has been reported that, γδ T cells, a type of cytotoxic lymphocyte, play a critical role in restricting EBV. However, the functional status of γδ T cells in pediatric CAEBV patients has not yet been described. In this study, flow cytometry analysis was conducted to explore the cytokine production capacity of γδ T cells in CAEBV patients. A diminished frequency of γδ T cells and decreased expression of cytolytic molecule granzyme B were found in CAEBV patients, suggesting a dysfunction in the immune regulatory function of γδ T cells in this disease. [ABSTRACT FROM AUTHOR]

Background: The first 24 h of infection represent a critical time window in interactions between pathogens and host tissue. However, it is not possible to study such early events in human lung during natural infection due to lack of clinical access to tissue this early in infection. We, therefore, applied RNA sequencing to ex vivo cultured human lung tissue explants (HLTE) from patients with emphysema to study global changes in small noncoding RNA, mRNA, and long noncoding RNA (lncRNA, lincRNA) populations during the first 24 h of infection with influenza A virus (IAV), Mycobacterium bovis Bacille Calmette-Guerin (BCG), and Pseudomonas aeruginosa. Results: Pseudomonas aeruginosa caused the strongest expression changes and was the only pathogen that notably affected expression of microRNA and PIWI-associated RNA. The major classes of long RNAs (> 100 nt) were represented similarly among the RNAs that were differentially expressed upon infection with the three pathogens (mRNA 77–82%; lncRNA 15–17%; pseudogenes 4–5%), but lnc-DDX60-1, RP11-202G18.1, and lnc-THOC3-2 were part of an RNA signature (additionally containing SNX10 and SLC8A1) specifically associated with IAV infection. IAV infection induced brisk interferon responses, CCL8 being the most strongly upregulated mRNA. Single-cell RNA sequencing identified airway epithelial cells and macrophages as the predominant IAV host cells, but inflammatory responses were also detected in cell types expressing few or no IAV transcripts. Combined analysis of bulk and single-cell RNAseq data identified a set of 6 mRNAs (IFI6, IFI44L, IRF7, ISG15, MX1, MX2) as the core transcriptomic response to IAV infection. The two bacterial pathogens induced qualitatively very similar changes in mRNA expression and predicted signaling pathways, but the magnitude of change was greater in P. aeruginosa infection. Upregulation of GJB2, VNN1, DUSP4, SerpinB7, and IL10, and downregulation of PKMYT1, S100A4, GGTA1P, and SLC22A31 were most strongly associated with bacterial infection. Conclusions: Human lung tissue mounted substantially different transcriptomic responses to infection by IAV than by BCG and P. aeruginosa, whereas responses to these two divergent bacterial pathogens were surprisingly similar. This HLTE model should prove useful for RNA-directed pathogenesis research and tissue biomarker discovery during the early phase of infections, both at the tissue and single-cell level. [ABSTRACT FROM AUTHOR]

AbstractIn this paper, Wolbachia infection in a bisexual and diploid population with a fixed cytoplasmic incompatibility rate w and maternal transmission rate d is studied as an evolution algebra. As the cytoplasmic incompatibility (CI) of the population causes deaths in the offspring, the evolution algebra of this model is not baric, and is a dibaric algebra if and only if the cytoplasmic incompatibility rate w is 1 and d=1 . The idempotent elements are given in terms of d and w. Moreover, this algebra has no absolute nilpotent elements when CI expression w≠1 . [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aims Methods Results Conclusions Given the introduction of new advanced therapies for inflammatory bowel diseases (IBDs), expanded risk mitigation strategies are essential.To create a comprehensive set of statements on assessment procedures and vaccinations before starting monoclonal antibodies, Janus kinase (JAK) inhibitors or sphingosine‐1‐phosphate (S1P) modulators for IBD.We examined literature, guidelines and drug product information regarding vaccination and assessment recommendations for initiating advanced IBD therapies. Using a modified Delphi approach, delegates voted anonymously on the acceptability of these statements prior to and following consensus discussion.We developed eight statements on the domains of infectious diseases screening, vaccinations and assessments prior to commencing JAK inhibitors and S1P modulators. Six statements received agreement. Pre‐advanced therapy screening for infectious diseases was established, and the vaccination protocol was revised. Malignancy, cardiovascular and thromboembolic risk assessments are necessary before initiating JAK inhibitors. Those starting S1P modulators need cardiac and ophthalmic assessments.These consensus statements combine vaccination and assessments on the currently available advanced therapies for IBD as a single comprehensive document that may reduce IBD complications associated with use of advanced therapies. Knowledge gaps identified during the consensus process will provide further research opportunities. [ABSTRACT FROM AUTHOR]

AbstractPseudomonas aeruginosa is a versatile Gram-negative pathogen known for its ability to invade the respiratory tract, particularly in cystic fibrosis patients. This review provides a comprehensive analysis of the multifaceted strategies for colonization, virulence, and immune evasion used by P. aeruginosa to infect the host. We explore the extensive protein arsenal of P. aeruginosa, including adhesins, exotoxins, secreted proteases, and type III and VI secretion effectors, detailing their roles in the infective process. We also address the unique challenge of treating diverse lung conditions that provide a natural niche for P. aeruginosa on the airway surface, with a particular focus in cystic fibrosis. The review also discusses the current limitations in treatment options due to antibiotic resistance and highlights promising future approaches that target host-pathogen protein-protein interactions. These approaches include the development of new antimicrobials, anti-attachment therapies, and quorum-sensing inhibition molecules. In summary, this review aims to provide a holistic understanding of the pathogenesis of P. aeruginosa in the respiratory system, offering insights into the underlying molecular mechanisms and potential therapeutic interventions. [ABSTRACT FROM AUTHOR]

Chronic wounds significantly burden health care systems worldwide, requiring novel strategies to ease their impact. Many physiological processes underlying wound healing are well studied but the role of mast cells remains controversial. Mast cells are innate immune cells and play an essential role in barrier function by inducing inflammation to defend the host against chemical irritants and infections, among others. Many mast cell–derived mediators have proposed roles in wound healing; however, in vivo evidence using mouse models has produced conflicting results. Recently, studies involving more complex wound models such as infected wounds, diabetic wounds and wounds healing under psychological stress suggest that mast cells play critical roles in these processes. This review briefly summarizes the existing literature regarding mast cells in normal wounds and the potential reasons for the contradictory results. Focus will be placed on examining more recent work emerging in the last 5 years that explores mast cells in more complex systems of wound healing, including infection, psychological stress and diabetes, with a discussion of how these discoveries may inspire future work in the field. [ABSTRACT FROM AUTHOR]

The aim of this meta‐analysis is to compare the clinical outcomes in patients with and without residual osteomyelitis (ROM) after surgical bone resection for diabetic foot osteomyelitis (DFO). We completed a systematic literature search using PubMed, Scopus, and Embase using keywords DFO, Residual OM (ROM), and positive bone margins. The study outcomes included wound healing, antibiotic duration, amputation, and re‐infection. Five hundred and thirty patients were included in the analysis; 319 had no residual osteomyelitis (NROM), and 211 had ROM. There was not a significant difference in the proportion of wounds that healed 0.6 (p = 0.1, 95% confidence intervals [95% CI] 0.3–1.3). The risk of infection was 2.0 times higher (OR = 2.0, p = 0.02, 95% CI 1.1–3.4), and the risk of amputation was 4.3 times higher (OR = 4.3, p = 0.0001, 95% CI 2.4–7.6) in patients with ROM. Patients with ROM received antibiotics significantly longer. The mean difference was 16.3 days (p = 0.02, 95% CI 11.1–21.1). [ABSTRACT FROM AUTHOR]

We study SIR‐type epidemics (susceptible‐infected‐resistant) on graphs in two scenarios: (i) when the initial infections start from a well‐connected central region and (ii) when initial infections are distributed uniformly. Previously, Ódor et al. demonstrated on a few random graph models that the expectation of the total number of infections undergoes a switchover phenomenon; the central region is more dangerous for small infection rates, while for large rates, the uniform seeding is expected to infect more nodes. We rigorously prove this claim under mild, deterministic assumptions on the underlying graph. If we further assume that the central region has a large enough expansion, the second moment of the degree distribution is bounded and the number of initial infections is comparable to the number of vertices, the difference between the two scenarios is shown to be macroscopic. [ABSTRACT FROM AUTHOR]

Evolving evidence suggests that Janus Kinase Inhibitors (JAKi) may predispose to certain infections, including tuberculosis and human herpes viruses. This review aimed to compare the infection risk in patients on a systemic JAKi for a dermatologic indication to a placebo. A systematic review was carried out from inception to June 2023, using the EMBASE, Medline, SCOPUS, and Cochrane Library of Registered Trials databases. Eligible studies included placebo‐controlled randomized trials that investigated the incidence of infection in patients with a dermatologic indication. Primary outcomes included the most commonly reported infections pertaining to serious and opportunistic infections, upper respiratory tract infections, nasopharyngitis, herpes simplex, varicella zoster, tuberculosis, neutropenia, and lymphopenia. A meta‐analysis of incidence ratios was conducted to determine odds ratios (OR), with a 95% confidence interval (CI) analysis. The meta‐analysis found no increased risk of serious (OR: 0.92, 95% CI: 0.61–1.43, P = 0.74) or opportunistic infections (OR: 0.65, 95% CI: 0.32–1.31, P = 0.23). The incidence of varicella‐zoster infections was significantly higher in the JAKi cohort (OR: 1.72, 95% CI: 1.08–2.72, P = 0.022). From 25 studies, there was no overall increased risk of herpes simplex infections (OR: 1.43, 95% CI: 0.93–2.23, P = 0.102) to placebo; however, a significantly higher risk in those with atopic dermatitis to alopecia areata was demonstrated (OR: 1.73, 95% CI: 1.13–2.69, P = 0.013). The results of this analysis do not suggest an increased risk of serious and opportunistic infections in those on JAKi compared to placebo. However, they support an increased risk of varicella‐zoster infections and a higher risk of herpes simplex infections in those with atopic dermatitis to alopecia areata. The results of this report support these agents' short‐term safety but signal that vigilance should be practiced in patients at risk for serious or recurrent herpes virus infections. [ABSTRACT FROM AUTHOR]

Clostridioides difficile infection (CDI) is an urgent public health threat with limited preventative options. In this work, we developed a messenger RNA (mRNA)-lipid nanoparticle (LNP) vaccine targeting C. difficile toxins and virulence factors. This multivalent vaccine elicited robust and long-lived systemic and mucosal antigen-specific humoral and cellular immune responses across animal models, independent of changes to the intestinal microbiota. Vaccination protected mice from lethal CDI in both primary and recurrent infection models, and inclusion of non-toxin cellular and spore antigens improved decolonization of toxigenic C. difficile from the gastrointestinal tract. Our studies demonstrate mRNA-LNP vaccine technology as a promising platform for the development of novel C. difficile therapeutics with potential for limiting acute disease and promoting bacterial decolonization. [ABSTRACT FROM AUTHOR]

Background Objective Animals Methods Results Conclusion and Clinical Importance Minimally invasive approaches are the standard for treatment of upper urinary tract uroliths in humans.To describe the medical dissolution of upper urinary tract uroliths in a series of dogs and report clinical outcomes.6 female dogs (9 kidneys).Retrospective case series. A review of medical records in dogs that underwent medical dissolution of upper urinary tract uroliths utilizing diet, administration of antibiotics, and double‐pigtail ureteral stent(s) placement, when indicated, was performed. Medical management was generally continued for 4 weeks beyond urolith dissolution. Information on biochemical, microbiological, imaging, and clinical outcomes before and after dissolution were recorded.Six dogs (9 kidneys) were included with bilateral (3) or unilateral (3) nephrolithiasis, ureterolithiasis, or a combination. A ureteral stent(s) was placed endoscopically in 5/6 dogs (6/9 kidneys) for obstructive ureterolithiasis (n = 5) or a nonobstructive massive nephrolith (n = 1). All dogs had a positive urine culture of Staphylococcus pseudintermedius with a median urine pH of 7.25 (range, 6.5‐8) and 4/5 had pyonephrosis. All dogs had initial evidence of urolith dissolution at a median of 1.1 months (range, 0.42‐5.9), with complete dissolution of ureteroliths at a median of 3.9 months (range, 1.5‐7.6), nephroliths at 5.3 months (range, 1.5‐7.6), and lower urinary tract uroliths at 0.87 months (range, 0.42‐5.9). Stents were removed in 3/6 once dissolution was documented. The median follow‐up time was 519 days (range, 177‐2492 days).Medical dissolution and decompression of upper urinary tract struvite uroliths should be considered a minimally invasive treatment for dogs before more invasive options. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusions Infections and vaccinations have been identified as potential immunological triggers of neuralgic amyotrophy (NA), but the exact type and frequency of the preceding agents is unknown.This was a multicentre, prospective, observational, matched case–control study. NA was diagnosed by neuromuscular experts according to validated clinical criteria and electrodiagnostic studies. Clinical data and biological samples of NA patients were collected within 90 days from disease onset between June 2018 and December 2023. All NA patients were asked about prior infection and vaccination in the month before disease onset. Serological tests for hepatitis E virus, human immunodeficiency virus, severe acute respiratory syndrome coronavirus 2, Epstein–Barr virus, cytomegalovirus, parvovirus B19, varicella‐zoster virus, Borrelia burgdorferi, Mycoplasma pneumoniae and Bartonella henselae were performed in a central laboratory. Each case was matched with a healthy control for age, sex, place of residence and time of blood collection.Fifty‐seven patients and corresponding controls were included. The mean age was 45 years for both groups. NA onset was preceded by a symptomatic infectious trigger confirmed by microbiological tests in 15/57 (26.3%) patients. Coronavirus disease 2019 vaccination was considered a potential trigger in 7/57 (12.3%) subjects. An acute viral infection was associated with a bilateral involvement of the brachial plexus (p = 0.003, Cramèr's V = 0.43).Confirmed immune triggers (infection or vaccination) preceded disease onset in 22/57 (38.6%) NA cases. We suggest to test NA patients in the acute phase for intracellular antigens, especially in the case of concomitant bilateral involvement and hepatitis. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionHelicobacter pylori (HP), which colonizes exclusively in the gastrointestinal tract, has been reported to dysregulate the immune response and gives rise to several extra-gastrointestinal autoimmune disorders. However, the relationship between HP and immune-mediated ocular diseases remains ambiguous. This study aims to clarify the association between immune-mediated ocular diseases and HP infection, as well as the impact of HP treatment on the incidence of immune-mediated ocular diseases.This is a retrospective population-based study using National Health Insurance Research Database in Taiwan. Patients with newly diagnosed peptic ulcer disease or HP infection between 2009 and 2015 were identified as HP group and compared to the non-HP group with one-to-one exact matching. Moreover, the incident risk of immune-mediated ocular diseases and its two subgroups (ocular surface and orbital inflammation group, intraocular inflammation group) were compared in HP patients with or without treatment.A total of 1,030,119 subjects in the non-HP group and 1,030,119 patients in the HP group were enrolled. The incidence rate of immune-mediated ocular diseases was significantly higher in the HP group (95% confidence interval (CI): 2.534–2.547). The incident rate ratio was significantly higher in HP with treatment than without treatment (HR: 1.654, 95% CI: 1.641–1.668). The Cox proportional hazards regression model demonstrated a significantly increased HR of immune-mediated ocular diseases in HP treated group (HR: 2.265, 95% CI: 2.024–2.534) and less increased HR in HP non-treated group (HR: 1.427, 95% CI: 1.273–1.598) when comparing to non-HP group. Subgroup analysis demonstrated a significantly higher incidence rate of ocular surface and orbital inflammation as well as intraocular inflammation in the HP group.This study illustrated a higher incidence of immune-mediated ocular diseases in HP infection, and a heightened risk following HP eradication. [ABSTRACT FROM AUTHOR]

Background/Objectives: As a primary source of mortality and disability, bacterial infections continue to develop a severe threat to humanity. Nuclear medicine imaging (NMI) is known for its promising potential to diagnose deep-seated bacterial infections. This work aims to develop a new technetium-99m (99mTc) labeled tigecycline radiopharmaceutical as an infection imaging agent. Methods: Reduced 99mTc was used to make a coordinate complex with tigecycline at pH 7.7–7.9 at room temperature. Instantaneous thin-layer chromatography impregnated with silica gel (ITLC-SG) and ray detector equipped high-performance liquid chromatography (ray-HPLC) was performed to access the radiolabeling yield and radiochemical purity (RCP). Results: More than 91% labeling efficiency was achieved after 25 min of mild shaking of the reaction mixture. The radiolabeled complex was found intact up to 4 h in saline. Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) infection-induced rats were used to record the biodistribution of the radiopharmaceutical and its target specificity; 2 h' post-injection biodistribution revealed a 2.39 ± 0.29 target/non-target (T/NT) ratio in the E. coli infection-induced animal model, while a 2.9 ± 0.31 T/NT value was recorded in the S. aureus bacterial infection-induced animal model. [99mTc]Tc-tigecycline scintigraphy was performed in healthy rabbits using a single photon emission computed tomography (SPECT) camera. Scintigrams showed normal kidney perfusion and excretion into the bladder. Conclusion: In conclusion, the newly developed [99mTc]Tc-tigecycline radiopharmaceutical could be considered to diagnose broad-spectrum bacterial infections. [ABSTRACT FROM AUTHOR]

Hepcidin production is regulated by iron concentration, erythropoietic activity, and inflammation. There is no reference method for determining its levels, but results obtained through various methods strongly correlate and can be compared using recalibration equations. Objective: To describe recalibrated serum hepcidin values at different percentiles in schoolchildren, considering age, sex, inflammatory processes, H. pylori infection, and iron status. Methods: Secondary analysis of data incorporating information on inflammation, H. pylori infection, and iron status of 349 schoolchildren. Hepcidin analysis was performed using a competitive ELISA, and recalibrated hepcidin values were calculated using the inverse of the linear regression model equation obtained by van der Vorm et al. Results: Recalibrated hepcidin values were lower than non-calibrated values. In schoolchildren without infection/inflammation and without iron deficiency, recalibrated values at the 50th percentile (25th–75th) were 4.89 ng/mL (2.68–8.42). For schoolchildren without infection/inflammation but with iron deficiency, recalibrated values were 2.34 ng/mL (1.10–6.58), the lowest hepcidin values observed. The highest values were found in the group with infection/inflammation, regardless of iron deficiency status. Conclusions: Recalibrated hepcidin values were lower than non-calibrated values. The highest values were observed in schoolchildren with infectious or inflammatory processes, and the lowest values were observed in schoolchildren with iron deficiency but only in the absence of infectious or inflammatory processes. Using recalibrated hepcidin values allows comparison between data obtained using different analytical methods. [ABSTRACT FROM AUTHOR]

Problem: Preterm birth (PTB) is a significant cause of maternal and neonatal morbidity and mortality worldwide. However, the effectiveness of progesterone (P4) which is clinically used for PTB management remains controversial and necessitates research into new therapeutic options Method of Study: In the current study, we investigated the effectiveness of two chlorophyll derivatives, pheophorbide a (PBa) and pheophytin a (PTa), in counteracting PTB. Timed‐pregnant mice (gestation day 17 ± 0.5) received lipopolysaccharide (LPS) (25 µg/mouse) or phosphate‐buffered saline (PBS) intraperitoneally, with PBa, PTa, progesterone (P4), and co‐administration of P4 and ibuprofen (IBP), administered orally 2 h prior. Results: The LPS group experienced PTB and 100% fetal mortality, whereas the PBa and PTa groups showed a delayed onset of LPS‐induced PTB, with significantly decreased PTB rate and fetal mortality. In addition, PBa and PTa suppressed LPS‐induced pro‐inflammatory cytokines and NF‐κB transcription factor while increasing anti‐inflammatory cytokines in the placenta and uterus. Conclusions: Our findings indicate that the chlorophyll derivatives, PBa and PTa increase fetal survival in infection‐induced PTB and demonstrate greater efficacy than P4 in preventing PTB. [ABSTRACT FROM AUTHOR]

Objectives Patients with reported Stenotrophomonas maltophilia (S. maltophilia) growth in lower respiratory tract samples were investigated. The results of these patients were assessed by clinicians as either infection or colonization. The data of patients considered to have S. maltophilia infection were compared to those considered to have colonization to explore factors associated with infection. Methods Parameters including as age, length of hospital stay, duration of S. maltophilia growth after hospital admission, sex, unit, department, specimen type, mechanical ventilation treatment status, antimicrobial susceptibility results, comorbidities, survival, and antimicrobials used during the period from hospital admission to S. maltophilia growth were investigated. Additionally, some biochemical parameters that were examined include the day of hospital admission, the day of sample collection when the bacterium was isolated (±1 day), and the day of discharge/died. Results The infection group had a significantly higher rate of admissions to internal medical departments and more cases of discharge/died. The infection group showed a lower amount of aminoglycoside antibiotic usage and significantly higher levels of BUN, creatinine, neutrophils, and neutrophil-to-lymphocyte ratio on their day of discharge/died. Conclusion Being admitted to internal medical departments and receiving aminoglycoside treatment were identified to be factors associated with S. maltophilia infection. These patients should be monitored for infection markers such as CRP and neutrophil count, as well as renal function tests. It should be noted that being infected with S. maltophilia is an independent risk factor for mortality. [ABSTRACT FROM AUTHOR]

The bond between humans and dogs is precious and has been treasured since ancient times. Dog ownership is linked to numerous health benefits, such as increased physical activity and social functioning and decreased depression and cardiovascular events. However, dogs can transmit zoonotic diseases to humans, many of which present with cutaneous findings. This review summarizes the dermatologic manifestations, transmission routes, diagnosis, and treatment of zoonotic diseases transmitted by dogs, including vector‐borne, bacterial, viral, fungal, and parasitic infections. This review emphasizes the significance of clinicians obtaining a comprehensive exposure history when patients exhibit a rash of unknown origin. Such an approach can provide valuable epidemiological clues related to diagnosing a zoonotic disease transmitted by a pet dog. Furthermore, identifying the dog as an infection source and subsequent veterinary treatment can help prevent recurrent infections in dermatologic patients. [ABSTRACT FROM AUTHOR]

Introduction: COVID-19 can have long-lasting effects, but the effects on blood parameters and inflammation are poorly understood. The aim of this study was to evaluate morphological and inflammatory markers in long-term COVID-19 patients. Aim: To evaluate complete blood count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and morphology in mild versus severe long COVID-19. Material and methods: In total, 39 long COVID-19 patients were stratified into mild (n = 25) and severe (n = 14) groups. Blood counts, NLR, PLR were measured. Cell morphology was analysed. ROC curves were used to determine biomarker thresholds. Survival was assessed using Kaplan-Meier curves. Results and discussion: Severe patients had lower leukocytes but higher neutrophils, indicating greater inflammation. NLR and PLR were significantly increased in severe patients compared to mild patients (NLR 12 vs 8; PLR 140 vs 100). NLR and PLR were higher than in controls, confirming their utility as inflammatory markers. NLR and PLR effectively discriminated between mild and severe disease. High NLR and PLR predicted poorer prognosis. Altered leukocyte morphology such as cytoplasmic vacuolization correlated with severity. Conclusions: NLR and PLR are promising biomarkers for assessing severity of long COVID-19, while morphological changes in blood cells provide additional evidence of inflammation. Further studies in larger populations are warranted. [ABSTRACT FROM AUTHOR]

Background: Population‐based studies describing the association between diabetes and increased risk of infection have largely been based in high‐income countries. There is limited information describing the burden of infectious disease attributable to diabetes in low and middle‐income countries. This study aimed to describe the burden and risk of infectious disease hospitalisation in people with diabetes compared to those without diabetes in northeastern Thailand. Methods: In a retrospective cohort study using electronic health record data for 2012–2018 for 3.8 million people aged ≥20 years in northeastern Thailand, hospitalisation rates for any infectious diseases (ICD‐10 codes A00‐B99) were estimated and negative binomial regression used to estimate rate ratios (RR) for the association between diabetes and infectious disease hospitalisation adjusted for age, sex and area of residence. Results: In this study, 164,177 people had a diagnosis of diabetes mellitus at any point over the study period. Infectious disease hospitalisation rates per 1000 person‐years (95%CI) were 71.8 (70.9, 72.8), 27.7 (27.1, 28.3) and 7.5 (7.5, 7.5) for people with prevalent diabetes, incident diabetes and those without diabetes respectively. Diabetes was associated with a 4.6‐fold higher risk of infectious disease hospitalisation (RR (95% CI) 4.59 (4.52, 4.66)). RRs for infectious disease hospitalisation were 3.38 (3.29, 3.47) for people with diabetes managed by lifestyle alone and 5.29 (5.20, 5.39) for people receiving prescriptions for diabetes drugs. Conclusions: In this Thai population, diabetes was associated with substantially increased risk of hospitalisation due to infectious diseases and people with diabetes who were on pharmacological treatment had a higher risk than those receiving lifestyle modification advice alone. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to describe the use of retrograde gentamicin-coated tibial intramedullary nail (ETN PROtect™) in patients with tibial defects who required a tibiotalocalcaneal arthrodesis (TTC). Methods: Consecutive series case review of seven men treated with TTC using retrograde PROtect™ between January 2018 and December 2023. The main outcomes evaluated were fracture union, complications, and the health-related quality of life using the EuroQol five-dimension three-level questionnaire (EQ-5D-3L). Results: The mean age was 45.3 ± 8.0 years. Six patients had a clinical history of chronic osteomyelitis, and one case underwent TTC for congenital pseudoarthrosis. Fracture union was achieved in 5 of 7 patients between 4 and 11 months after surgery. Three patients developed complications; two patients had fistulas, and one had persistent pain. At the end of the follow-up, a median of 70 points (interquartile range: 60 to 90) on the EQ-5D-3L was reported. No complications directly attributed to the use of the PROtect™ were reported. Conclusion: TTC with retrograde PROtect™ is a prophylactic treatment option in patients with tibial defects treated with external fixation requiring a tibiotalar and subtalar arthrodesis. This novel use of PROtect™ allows simultaneous fixation of the tibiotalocalcaneal joint and protection of the regenerated bone, facilitating earlier rehabilitation in patients at high risk for postoperative infections. [ABSTRACT FROM AUTHOR]

Background: The pararectus approach is a minimally invasive surgical approach for anterior acetabulum fracture, with an advantage of the medial window of the modified Stoppa approach (MSA). However, it is unclear whether the pararectus approach is superior to MSA. We aimed this systematic review and meta-analysis to compare the outcomes and complications of pararectus and MSA. Methods: We performed a data search by conducting an electronic search across databases of PubMed, Embase, Scopus, Cinahl, CNKI, and Cochrane Library and included seven comparative studies for analysis. Statistical analysis was performed using the RevMan software 5.4.1. The risk of bias was evaluated using the Cochrane Collaboration's risk of bias tool for RCTs and the MINORS tool for non-RCTs. Results: Two randomized control trials (RCTs), one prospective study, and four retrospective studies were included. Meta-analysis revealed a better Matta's reduction quality [OR 1.58, 95% CI 1.06, 2.37; p = 0.03] and radiological outcome [OR 2.18, 95% CI 1.03, 4.60; p = 0.04] in MSA than in pararectus approach. However, the pararectus approach has less intraoperative blood loss [MD – 9.79 (95% CI − 176.75, − 6.83; p = 0.03)] and a shorter hospital stay [MD − 2.61 (95% CI − 5.03, −.18; p = 0.04)] than MSA. Both approaches have failed to show a difference concerning overall complication rates [OR 0.66 (95% CI 0.28, 1.55; p = 0.34)], postoperative infection, DVT, duration of surgery [MD − 15.09 (95% CI − 35.38, 5.20; p = 0.15)], functional outcome, and incision length. Conclusion: The pararectus approach offers an advantage with lesser operative blood loss and shorter hospital stay, whilst MSA stands out with better reduction quality and radiological outcomes. Nevertheless, both approaches exhibit no difference in complication rates, duration of surgery, incision length, and functional outcome. Hence, the pararectus approach can be considered an alternative to MSA; however, the existing literature fails to demonstrate a distinct advantage over MSA. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy and postoperative infection rate of super mini percutaneous nephrolithotomy (SMP) and flexible ureteroscopic lithotripsy (FURL) in patients with diabetic nephrolithiasis and to explore the risk factors associated with postoperative infection following these two procedures. Methods: The medical history and surgery details of 252 patients with diabetic nephrolithiasis who underwent lithotripsy in our hospital between January 2018 and May 2023, including 144 SMP and 108 FURL, were reviewed and compared. Perioperative outcomes were compared between the two groups. Logistic regression was performed to identify the significant risk factors for infection after each procedure. Results: SMP achieved a higher stone-free rate (SFR) on postoperative day 1 and postoperative day 30 compared with FURL (p < 0.05). The mean operative time was shorter in SMP (p < 0.01). FURL was associated with less hemoglobin drop (p < 0.01) and shorter length of stay (p < 0.01). The incident rate of systemic inflammatory response syndrome (SIRS) was higher after SMP (p = 0.019), while the incident rate of urinary tract infection (UTI) was higher after FURL (p = 0.021). Overall postoperative infection and sepsis rates were similar between the two procedures. Logistic regression analysis revealed that gender odds ratio [OR]: 0.225, 95% confidence interval [CI]: 0.079–0.639), HbA1c (OR: 3.516, 95% CI: 1.841–6.716), and operation time (OR: 1.037, 95% CI: 1.008–1.066) were independent risk factors for infection after FURL, while operation time (OR: 1.063, 95% CI: 1.022–1.106) and HbA1c (OR: 7.443, 95% CI: 2.956–18.742) significantly predicted SMP-associated infections. Conclusion: In diabetic patients, SMP demonstrated higher SFR and shorter operation time, whereas FURL was associated with less bleeding and shorter hospitalization. SMP had a higher incident rate of SIRS and FURL had a higher incident rate of UTI. Elevated HbA1c and prolonged operative duration increased infection risk after both procedures, while female gender was an additional risk factor for FURL-related 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]

Fracture-related infection (FRI) is a devastating event, directly affecting fracture healing, impairing patient function, prolonging treatment, and increasing healthcare costs. Time plays a decisive role in prognosis, as biofilm maturation leads to the development of antibiotic resistance, potentially contributing to infection chronicity and increasing morbidity and mortality. Research exploring the association between biofilm maturation and antibiotic resistance in orthopaedics primarily addresses aspects related to quality of life and physical function; however, little exists on life-threatening conditions and mortality. Understanding the intrinsic relationship between biofilm maturation, bacterial resistance, and mortality is critical in all fields of medicine. In the herein narrative review, we summarize recent evidence regarding biofilm formation, antibiotic resistance, and infection chronicity (BARI), the three basic components of the "triangle of death" of FRI, and its implications. Preoperative, perioperative, and postoperative prevention strategies to avoid the "triangle of death" of FRI are presented and discussed. Additionally, the importance of the orthopaedic trauma surgeon in understanding new tools to combat infections related to orthopaedic devices is highlighted. [ABSTRACT FROM AUTHOR]