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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]

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]

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]

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]

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]

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]

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]

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]

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]

Aim Methods Results Conclusion Cerebral venous thrombosis (CVT) is a rare complication of ear, nose and throat (ENT) infections. Although recent guidelines recommend the systematic use of anti‐coagulation therapy (ACT) in the treatment of these CVT, literature data are scarce. The present study's objective was to determine the value of ACT in achieving recanalisation after thrombosis and its effect on patient outcomes.All paediatric patients with CVT and a concomitant ENT infection who attended Lille University Hospital (Lille, France) between January 2012 and December 2021 were retrospectively included.We included 43 children (63% boys), with a mean age of 4 years. The most frequent infection was mastoiditis (54%). ACT was initiated in 23 patients (53%), one of whom had an intracranial haemorrhage. Partial or full recanalisation was observed in 33 (80%) of the 41 survivors. In patients with no neurological signs and symptoms on admission and in patients with mastoiditis‐related CVT, the clinical and radiological outcomes were favourable and did not differ according to the administration of ACT. Likewise, ACT did not appear to influence the recanalisation rate or sequelae.ACT was not necessary for all patients with mastoiditis‐related CVT and those with no neurological signs and symptoms on admission. [ABSTRACT FROM AUTHOR]

Summary Inflammasomes are multi‐protein complexes that assemble within the cytoplasm of mammalian cells in response to pathogen‐associated molecular patterns (PAMPs) or damage‐associated molecular patterns (DAMPs), driving the secretion of the pro‐inflammatory cytokines IL‐1β and IL‐18, and pyroptosis. The best‐characterized inflammasome complexes are the NLRP3, NAIP‐NLRC4, NLRP1, AIM2, and Pyrin canonical caspase‐1‐containing inflammasomes, and the caspase‐11 non‐canonical inflammasome. Newer inflammasome sensor proteins have been identified, including NLRP6, NLRP7, NLRP9, NLRP10, NLRP11, NLRP12, CARD8, and MxA. These inflammasome sensors can sense PAMPs from bacteria, viruses and protozoa, or DAMPs in the form of mitochondrial damage, ROS, stress and heme. The mechanisms of action, physiological relevance, consequences in human diseases, and avenues for therapeutic intervention for these novel inflammasomes are beginning to be realized. Here, we discuss these emerging inflammasome complexes and their putative activation mechanisms, molecular and signaling pathways, and physiological roles in health and disease. [ABSTRACT FROM AUTHOR]

Exposure to infectious or non‐infectious immune activation during early development is a serious risk factor for long‐term behavioural dysfunctions. Mouse models of maternal immune activation (MIA) have increasingly been used to address neuronal and behavioural dysfunctions in response to prenatal infections. One commonly employed MIA model involves administering poly(I:C) (polyriboinosinic‐polyribocytdilic acid), a synthetic analogue of double‐stranded RNA, during gestation, which robustly induces an acute viral‐like inflammatory response. Using electroencephalography (EEG) and infrared (IR) activity recordings, we explored alterations in sleep/wake, circadian and locomotor activity patterns on the adult male offspring of poly(I:C)‐treated mothers. Our findings demonstrate that these offspring displayed reduced home cage activity during the (subjective) night under both light/dark or constant darkness conditions. In line with this finding, these mice exhibited an increase in non‐rapid eye movement (NREM) sleep duration as well as an increase in sleep spindles density. Following sleep deprivation, poly(I:C)‐exposed offspring extended NREM sleep duration and prolonged NREM sleep bouts during the dark phase as compared with non‐exposed mice. Additionally, these mice exhibited a significant alteration in NREM sleep EEG spectral power under heightened sleep pressure. Together, our study highlights the lasting effects of infection and/or immune activation during pregnancy on circadian activity and sleep/wake patterns in the offspring. [ABSTRACT FROM AUTHOR]

Host populations often vary in the magnitude of coinfection they experience across environmental gradients. Furthermore, coinfection often occurs sequentially, with a second parasite infecting the host after the first has established a primary infection. Because the local environment and interactions between coinfecting parasites can both drive patterns of coinfection, it is important to disentangle the relative contributions of environmental factors and within‐host interactions to patterns of coinfection.Here, we develop a conceptual framework and present an empirical case study to disentangle these facets of coinfection. Across multiple lakes, we surveyed populations of five damselfly (host) species and quantified primary parasitism by aquatic, ectoparasitic water mites and secondary parasitism by terrestrial, endoparasitic gregarines. We first asked if coinfection is predicted by abiotic and biotic factors within the local environment, finding that the probability of coinfection decreased for all host species as pH increased. We then asked if primary infection by aquatic water mites mediated the relationship between pH and secondary infection by terrestrial gregarines.Contrary to our expectations, we found no evidence for a water mite‐mediated relationship between pH and gregarines. Instead, the intensity of gregarine infection correlated solely with the local environment, with the magnitude and direction of these relationships varying among environmental predictors.Our findings emphasize the role of the local environment in shaping infection dynamics that set the stage for coinfection. Although we did not detect within‐host interactions, the approach herein can be applied to other systems to elucidate the nature of interactions between hosts and coinfecting parasites within complex ecological communities. [ABSTRACT FROM AUTHOR]

It is poorly understood how solid peripheral tumors affect brain neuroimmune responses despite the various brain‐mediated side effects and higher rates of infection reported in cancer patients. We hypothesized that chronic low‐grade peripheral tumor‐induced inflammation conditions microglia to drive suppression of neuroinflammatory responses to a subsequent peripheral immune challenge. Here, Balb/c murine mammary tumors attenuated the microglial inflammatory gene expression responses to lipopolysaccharide (LPS) and live Escherichia coli (E. coli) challenges and the fatigue response to an E. coli infection. In contrast, the inflammatory gene expression in response to LPS or a toll‐like receptor 2 agonist of Percoll‐enriched primary microglia cultures was comparable between tumor‐bearing and ‐free mice, as were the neuroinflammatory and sickness behavioral responses to an intracerebroventricular interleukin (IL)‐1β injection. These data led to the hypothesis that Balb/c mammary tumors blunt the neuroinflammatory responses to an immune challenge via a mechanism involving tumor suppression of the peripheral humoral response. Balb/c mammary tumors modestly attenuated select circulating cytokine responses to LPS and E. coli challenges. Further, a second mammary tumor/mouse strain model (E0771 tumors in C57Bl/6 mice) displayed mildly elevated inflammatory responses to an immune challenge. Taken together, these data indicate that tumor‐induced suppression of neuroinflammation and sickness behaviors may be driven by a blunted microglial phenotype, partly because of an attenuated peripheral signal to the brain, which may contribute to infection responses and behavioral side effects reported in cancer patients. Finally, these neuroimmune effects likely vary based on tumor type and/or host immune phenotype. [ABSTRACT FROM AUTHOR]

This article explores the challenges of determining the viability of infectious agents in tissue samples. It discusses various methods used in histopathology, such as staining techniques and immunohistochemistry, to assess viability. The article also mentions the potential use of mRNA analysis to indicate active replication of infectious agents. The author acknowledges the limitations of current techniques and suggests that nucleic acid amplification from formalin-fixed, paraffin-embedded samples could provide a more accurate assessment of viability. The article emphasizes the need for improved methods to determine the viability of infectious agents in tissue samples and calls for further research in this area. [Extracted from the article]

Objective: Medical students are demanders and future suppliers of antibiotic use. Understanding their knowledge, attitude and practice is important for appropriately using antibiotics and controlling antibiotic resistance. The objective of this study was to assess the measurement properties of existed instruments and summarize measurement items and results. Methods: Five English and Chinese databases were searched to comprehensively identify related studies between January 2000 and May 2023. Included instruments were assessed using consensus‐based standards for the selection of health measurement instruments checklist. Descriptive tables and narrative texts were applied to summary the data. Results: Of 3524 studies identified, 25 were finally included, from which 22 measurement instruments were included. Of these, 14 instruments were found with adequate content validity, only one study reported structural validation process and two studies reported reliability test results. Similar items were divided into different dimensions in different studies. Gaps and misconceptions in knowledge and attitude were indicated in antibiotic use principles, including antibiotic use indications and selection. Conclusions: Limitations existed in the current measurement instrument including lacking validation, inconsistent classification of item and lacking item regarding the perspective of suppliers. Scientific tools for objective and accurate measure are needed. [ABSTRACT FROM AUTHOR]

The objective of the study was to compare outcomes in patients with complete surgical resection versus partial resection of diabetic foot osteomyelitis (OM). A post hoc analysis of 171 patients with OM was performed using data from two randomized clinical trials. OM was confirmed with bone culture or histopathology. Surgical culture specimens were obtained from resected bone and sent for histopathology and microbiology. Residual osteomyelitis (RO) was defined as a positive resected margin on culture or histopathology. No residual osteomyelitis (NRO) was defined as no growth from bone culture and no histopathological inflammation in the biopsy of the resection margin. Data from the 12‐month follow‐up were used to determine clinical outcomes. During the index hospitalization, NRO patients had significantly shorter duration of antibiotic therapy (NRO 21.0, 13.0–38.0 vs. RO 37.0, 20.8–50.0, p <0.01) and more amputations than patients with RO (NRO 89.9% vs. RO 60.9%, p <0.01). During the 12‐month follow‐up, patients with NRO also had significantly shorter duration of antibiotic therapy (NRO 42, 21.0–66.5 vs. RO 50.5, 35.0–75.0, p = 0.02). During the 12‐month follow‐up, there was no difference in ulceration at the same site (NRO 3.7%, RO 4.3% p = 0.85), hospitalization (NRO 32.6%, RO 34.8%, p = 0.76), total re‐infections (NRO 25.3%, RO 29.3%, p = 0.56), re‐infection with osteomyelitis (NRO 13.3% vs. 13.5%, p = 0.36), amputation (NRO 8.8%, RO 5.4%, p = 0.86) and time to wound healing in days (NRO 94, 41.0–365 vs. RO 106, 42.8–365, p = 0.77). Successful treatment of osteomyelitis was achieved by 86.7% and 86.5% of patients. During the index hospitalization, patients with no residual osteomyelitis had more amputations and were treated with antibiotics for a shorter duration. During the 12‐month follow‐up, patients with no residual osteomyelitis had shorter durations of antibiotics. There were no differences in re‐infection, amputation, re‐ulceration or hospitalization. Level of evidence: 1 [ABSTRACT FROM AUTHOR]

Infertility, affecting approximately 16% of the global population, has led to increased reliance on reproductive medicine. The impact of human papillomavirus (HPV) infection in one or both partners on outcomes of Assisted Reproduction Technologies (ART) remains unclear. This prospective cohort study aimed to evaluate prevalence and effects of HPV infection in subjects and couples candidates to ART. A total of n = 510 men and n = 246 women were included and n = 145 couples (n = 290 individuals) had both partners enrolled in the study. The HPV semen infection rate was 17% (95% CI: 14–20) with HPV‐42, HPV‐16, HPV‐53 and HPV‐51 as the most frequently detected genotypes. In women, 26% (95% CI: 21–32) tested HPV‐positive in cervical swabs. In 6% (95% CI: 3–11) of the couples, both partners were positive but only three couples shared the same genotypes (HPV‐16; HPV‐39, HPV‐51, and HPV‐42; HPV‐31). Follicular fluids were positive in 20% (95% CI: 11–33) of samples, showing genotype discrepancies with cervical tests. Semen treatment could not completely eliminate the virus in positive samples but reduced the positivity to one‐third. No significant differences in semen and embryological variables, clinical pregnancy and live birth rates, neonatal and obstetrics outcomes were observed in subjects with positivity in semen or cervix compared to respective negative groups. Cumulative live birth rates per oocyte retrieval in couples where both partners were negative or both were positive did not differ, being 37% (95% CI: 28%–47%) and 44% (95% CI: 19–73), respectively. In conclusion, HPV testing should not be considered a prerequisite for accessing ART treatments. Robust inferences for natural fertility cannot be made using our findings, as the ART setting does not fully reflect natural conditions. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus‐associated acute respiratory infection (RSV‐ARI) constitutes an emerging cause of morbidity in the adult population. The present retrospective study was aimed at identifying factors predictive of poor outcome that may be assessed at the first evaluation in the Emergency Department (ED). We included 275 adult patients with laboratory‐confirmed RSV‐ARI that required hospital admission from the ED between January 2018 and December 2019. Poor outcome (composite of progression to high‐flow oxygen therapy, non‐invasive or invasive mechanical ventilation, or intensive care unit admission, and/or 30‐day all‐cause mortality) occurred in 31 patients (11.2%). Immunosuppression was present in 59 patients (21.5%). Although bacterial co‐infection was rare, antibiotic therapy was commonly initiated. Ribavirin was administered in 10 patients. Cognitive impairment (odds ratio [OR]: 2.452; 95% confidence interval [CI]: 0.990–6.072), concurrent oral anticoagulation (OR: 3.099; 95 CI: 1.287–7.464) and a pulse oximetry oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) ratio <382 at ED admission (OR: 3.013; 95 CI: 1.306–6.950) were independent risk factors for poor outcome, whereas influenza vaccination in the current season was protective (OR: 0.324; 95% CI: 0.138–0.763). Various factors easily available at the ED are useful for early risk stratification in adult patients with RSV‐ARI. [ABSTRACT FROM AUTHOR]

The Epstein–Barr virus (EBV) is responsible for a spectrum of human diseases and demonstrates a considerable prevalence among various populations. Advances in molecular epidemiological research have enhanced our comprehension of EBV‐related pathologies. In this study, our objective was to examine the epidemiological profile and clinical features of EBV infection in Chongqing, China. We enrolled patients suspected of EBV‐related diseases who were admitted to the First Affiliated Hospital of Chongqing Medical University between May 2013 and November 2022. Inclusion criteria were based on those who underwent EBV‐specific immunofluorescence or plasma EBV‐DNA testing. Among 13 584 inpatients, the overall seropositivity rates for EBNA‐1‐IgG, EBV‐VCA‐IgM, EBV‐EA‐IgG, EBV‐EA‐IgA, EBV‐VCA‐IgA, and EBV‐DNA were 91.89%, 7.22%, 18.00%, 16.19%, 30.78%, and 18.00%, respectively. The seropositivity rate for EBNA‐1‐IgG steadily increased with age. The seropositivity rate for VCA‐IgM, an indicator of acute EBV infection, was highest in patients aged 11–20 years at 26.41%, decreasing to 2%–6% in older patients. Additionally, among 205 outpatients, the EBV‐DNA positivity rate was 14.15%. In 3670 individuals from health check‐up centers, the seropositivity rates for EBV‐EA‐IgA and EBV‐VCA‐IgA were 11.96% and 28.09%, respectively, and the EBV‐DNA positivity rate was 11.92%, all of which were lower than those in inpatients. Among the 762 EBV‐DNA positive inpatients, adults aged 31–40 years were the least affected, with a seropositivity rate of 12.00%, which increased with age. The most common diseases associated with primary EBV infection were infectious mononucleosis (IM) (35.49%), followed by EBV infection (14.15%) and pneumonia (7.19%). The most common diseases associated with EBV reactivation were pneumonia (16.80%), nasopharyngeal carcinoma (NPC) (11.02%), and autoimmune diseases (7.04%). Patients with hemophagocytic lymphohistiocytosis (HLH) had the highest viral load, significantly higher than those with NPC, pneumonia, and liver cirrhosis. This large‐scale retrospective study explores the epidemiological characteristics and disease spectrum of EBV infection across all age groups. The findings contribute to the improvement of diagnostic and management strategies for EBV infection. [ABSTRACT FROM AUTHOR]

Surveillance studies of Transmitted Drug Resistance (TDR) are crucial in tracking the evolution of HIV epidemiology. Our aim was to investigate TDR to nucleoside reverse transcriptase inhibitors (NRTIs), non‐nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase inhibitors (INIs), as well as to new drugs: lenacapavir, fostemsavir. Predictive sensitivity was evaluated for maraviroc and broadly neutralizing antibodies (bNAbs) (zinlirvimab and teropavimab). Between 2020 and 2023, 85 people with HIV (PWH) were diagnosed with primary HIV‐1 infection (PHI). Pol and env sequences were analyzed and TDR was characterized according to the French ANRS algorithm. The genotypic‐based prediction of bNAbs sensitivity was based on HIV env amino acid signatures I108, I201, F353 for teropavimab and N325, N332, H330 for zinlirvimab. TDR to NRTIs, NNRTIs, PIs and INIs was evidenced in 8.2%, 12.9%, 4.7%, and 5.9% strains, respectively. Ten viruses were CXCR4/dual mix. All viruses were susceptible to lenacapavir (100%) and 52% harbored resistance to fostemsavir. The genotypic profile was associated with a predictive positive value (PPV) > 83% of susceptibility to both teropavimab and zinlirvimab for 23 viruses (31%), while 22 (29%) had a PPV between 62% and 75%, suggesting reduced susceptibility to both bNAbs as soon as primary infection. The surveillance of TDR evidenced at the time of PHI is important with regard to new strategies for HIV patients with virological failure and global implementation of PrEP using NRTI, INI such as recently approved injectable cabotegravir, and future long‐acting drugs such as lenacapavir and bNAbs. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is a widespread infectious disease with high mortality. Hence, identifying valuable biomarkers for detecting the early changes in SFTS is crucial. In this study, we investigated the relationship between the difference in hematocrit (HCT) and serum albumin (ALB) levels (HCT‐ALB) and the prognosis of patients with SFTS virus infection. After excluding the patients who did not meet the SFTS diagnostic criteria, those with SFTS from the First Affiliated Hospital of Wannan Medical College were divided into a fatal and Nonfatal group based on their disease prognosis. A dynamic analysis of the daily laboratory data was conducted for 14 days following SFTS onset. A receiver operating characteristic (ROC) curve was used to evaluate the predictive value of HCT‐ALB. Another sample of patients with SFTS admitted to the First Affiliated Hospital of Nanjing Medical University was utilized to verify the study conclusions. A total of 158 patients with SFTS were included. Among them, 126 patients were categorized in the Nonfatal group and 32 in the fatal group, leading to a mortality rate of 20.25% (32/158). Univariate analysis of the laboratory test findings and ROC curve analysis showed that alanine aminotransferase (ALT), aspartate aminotransferase (AST), HCT‐ALB, and lactate dehydrogenase (LDH) had a relatively better ability to discriminate the disease condition of the patients with SFTS. Moreover, HCT‐ALB served as a predictor of SFTS prognosis. Additionally, an area under the ROC curve (AUC) of 0.777 and a critical HCT‐ALB value of 4.75 on day 7 were associated with a sensitivity of 83.3% and a specificity of 73.9%. On day 8 (AUC = 0.882), the critical value of HCT‐ALB was 9.25, while the sensitivity was 100% and specificity was 76.5%. Further verification based on the data of 91 patients with SFTS admitted to the First Affiliated Hospital of Nanjing Medical University demonstrated a mortality rate of 51% (24/47) among those with HCT‐ALB values >4.75 on day 7 of the disease course, highlighting the potential of the HCT‐ALB value of >4.75 for predicting SFTS prognosis. High HCT‐ALB values are closely related to the mortality of patients with SFTS. HCT‐ALB is a sensitive and independent predictor of early disease in patients with SFTS. [ABSTRACT FROM AUTHOR]

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Summary: Background and Objectives: Knowledge about the current spectrum of dermatomycoses is important for diagnosis and therapy. Patients and Methods: A retrospective, monocentric analysis of mucocutaneous fungal infections diagnosed at a large European academic dermatology department in Munich was conducted; 87,229 samples from 48,916 patients from January 1, 2011, to August 30, 2020, were included. Results: Fungi were detected in 11,513 samples from 48,916 (23.54%), and 36 different species were identified. Candida (C.) albicans was the most common pathogen (5,055 detections; 43.91% of all positive samples), followed by Trichophyton (T.) rubrum (3,076 detections; 26.72% of all positive samples) and Candida parapsilosis (923 detections; 8.02% of all positive samples). Rare pathogens such as Trichophyton raubitschekii were also detected. Coinfections with multiple species were detected in 44 cases. Conclusions: Even though C. albicans, T. rubrum, and C. parapsilosis were confirmed as the most common pathogens, rare pathogens should also be considered in clinical practice. The predominant spectrum of fungi differed from that reported in other countries. Furthermore, a difference in the pathogen spectrum could be observed depending on the age group and body site. [ABSTRACT FROM AUTHOR]

Migrating animals are thought to be important spillover sources for novel pathogens. Haemosporidians (malaria‐related parasites) are one such group of pathogens that commonly spillover into novel host communities if competent vectors are present. In birds, shorebirds (sandpipers, plovers and allies) perform some of the longest avian migrations, yet they are traditionally perceived as relatively free from haemosporidians. Although low prevalence fits several theories, such as effective immune responses or low exposure to vectors, few studies have been carried out in freshwater inland sites, where the vectors of haemosporidians (e.g. mosquitoes) are abundant, with a mixture of actively migrating (staging) and breeding hosts. Here we report the prevalence of three haemosporidian parasites, Haemoproteus, Leucocytozoon and Plasmodium, screened in 214 shorebirds from 15 species sampled in a freshwater marshland, southern Belarus. Contrary to most previous studies, we found that haemosporidians were frequent, with an overall prevalence in the community of 16.36%, including the locally breeding shorebirds (23.13%, 134 individuals of 10 species). However, actively migrating shorebirds had much lower prevalence (0.05%, 55 individuals of five species). We suggest that blood parasite infections are more common in shorebirds than currently acknowledged. Yet, actively migrating species may be free from haemosporidians or carry suppressed infections, leading to lower prevalence or even apparent absence in some species. Taken together, we theorize that a combination of sampling biases has driven our understanding of haemosporidian prevalence in shorebirds and future studies should take the migratory status of individuals into account when reporting prevalence. Furthermore, we argue that birds undergoing active migration may be less likely sources of spillover events than previously assumed. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is a frequent cause of antimicrobial‐resistant hospital‐acquired pneumonia, especially in critically ill patients. Inflammation triggered by P. aeruginosa infection is necessary for bacterial clearance but must be spatially and temporally regulated to prevent further tissue damage and bacterial dissemination. Emerging data have shed light on the pro‐resolving actions of angiotensin‐(1‐7) [Ang‐(1‐7)] signaling through the G protein‐coupled receptor Mas (MasR) during infections. Herein, we investigated the role of the Ang‐(1‐7)/Mas axis in pneumonia caused by P. aeruginosa by using genetic and pharmacological approach and found that Mas receptor‐deficient animals developed a more severe form of pneumonia showing higher neutrophilic infiltration into the airways, bacterial load, cytokines, and chemokines production and more severe pulmonary damage. Conversely, treatment of pseudomonas‐infected mice with Ang‐(1‐7) was able to decrease neutrophilic infiltration in airways and lungs, local and systemic levels of pro‐inflammatory cytokines and chemokines, and increase the efferocytosis rates, mitigating lung damage/dysfunction caused by infection. Notably, the therapeutic association of Ang‐(1‐7) with antibiotics improved the survival rates of mice subjected to lethal inoculum of P. aeruginosa, extending the therapeutic window for imipenem. Mechanistically, Ang‐(1‐7) increased phagocytosis of bacteria by neutrophils and macrophages to accelerate pathogen clearance. Altogether, harnessing the Ang‐(1‐7) pathway during infection is a potential strategy for the development of host‐directed therapies to promote mechanisms of resistance and resilience to pneumonia. [ABSTRACT FROM AUTHOR]

This paper is an educationally focused article discussing how transplant infectious diseases (TID) providers balance the risks of accepting or rejecting an organ and have pushed barriers in organ transplantation. We emphasize the role TID providers play in the transplantation process as critical players on the transplant team. We discuss various donor‐derived infections that were previously deemed unacceptable for donation due to concerns for transmission. Advances in medical knowledge have changed some of these situations. We discuss the critical role TID providers have in closing the gap between the thousands of patients on organ waitlists and the organ deficit faced each day. We believe TID providers have a unique opportunity to expand the donor pool by increasing education, expanding acceptable organ definitions, and expanding the boundaries of what we can do with potentially transmissible infections in organ transplantation. [ABSTRACT FROM AUTHOR]

Background Objective Animals Methods Results Conclusions and Clinical Importance Before the discovery of effective antiviral drugs, feline infectious peritonitis (FIP) was a uniformly fatal disease of cats. Multiple antiviral treatments have been recognized, but optimization of treatment protocols is needed.To evaluate the efficacy of PO molnupiravir (MPV; EIDD‐2801) to treat effusive FIP.Ten cats with naturally occurring effusive FIP and 10 historical control cats with effusive FIP treated with PO GS‐441524.A single‐center, prospective, open‐label longitudinal, non‐inferiority trial with historical controls. Ten cats with FIP were enrolled and treated with PO MPV (10‐15 mg/kg PO q12h) for 84 days. Cats were evaluated at 0, 6, and 16 weeks, and the proportion of cats in clinical remission at 16 weeks was determined. Survival and clinicopathologic features were compared with historical control cats with effusive FIP treated with PO GS‐441524.Eight of the 10 cats treated with MPV survived and were in remission at 16 weeks. The 2 non‐survivors died in the first 24 hours of treatment. No adverse events that necessitated discontinuation of treatment were observed. Survival of cats treated with PO MPV was non‐inferior to historic control cats treated with PO GS‐441524 (5/9 [55%] survived), with a difference in survival of 25% (90% confidence interval, −9.3% to 59.3%). Clinicopathologic features associated with FIP normalized during the study period, and no differences in clinicopathologic data at each study time point were observed when comparing cats treated with MPV and GS‐441524.Molnupiravir is an effective antiviral treatment for effusive FIP. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Cold atmospheric plasma (CAP) therapy has been recognized as effective treatment option for reducing bacterial load in chronic wounds, such as adult ventricular assist device (VAD) driveline exit‐site infections. Currently, there have been no reports on the safety and efficacy of CAP therapy for pediatric cannula infections and inflammations in paracorporeal pulsatile VADs.The mechanical strength of Berlin Heart EXCOR cannulas were tested both before and after CAP treatment (SteriPlas, Adtec Healthcare Limited, UK) to prove material safety. A ring tensile test of 20 untreated and 20 CAP‐treated (5 min) EXCOR cannulas (Ø12mm), assessed the force at the breaking point of the cannulas (Fmax), at 25% (F25%) and 50% (F50%) of the maximum displacement. Additionally, the scanning electron microscope (SEM) micrographs for both groups examined any surface changes. Finally, the case of a 13‐year‐old male EXCOR patient with cannula infections, treated with CAP over 100 days, is presented.The in vitro measurements revealed no statistically significant differences in mechanical strength between the control and CAP group for F25% (8.18 ± 0.36 N, vs. 8.02 ± 0.43 N, p = 0.21), F50% (16.87 ± 1.07 N vs. 16.38 ± 1.32 N, p = 0.21), and FMAX (44.55 ± 3.24 N vs. 42.83 ± 4.32 N, p = 0.16). No surface structure alterations were identified in the SEM micrographs. The patient's cannula exit‐sites showed a visible improvement in DESTINE wound staging, reduction in bacterial load and inflammatory parameters after CAP treatment without any side effects.Overall, CAP therapy proved to be a safe and effective for treating EXCOR cannula exit‐site wound healing disorders in one pediatric patient, but further studies should investigate this therapy in more detail. [ABSTRACT FROM AUTHOR]

The ability to impact the immune response of the host has been recognized as essential for the success of a virus during infection. A few groups of viruses can combine these immunomodulatory mechanisms with specific patterns of their own transcriptional and replication regulation to achieve persistence within the host long term. The Herpesvirales order is one of those groups and the resultant state is known as latency. Throughout the years, latency has been studied in many host‐herpesvirus models to attempt to understand the complex and profound effects of this state on the host's systems, and in the hopes of deciphering a way to eliminate the latent state from survivors of the primary infection. Most studies of herpesvirus latency have been conducted on mammalian host species, but this review summarizes the data available regarding herpesviruses in fish species and their latent state. As the field of aquatic animal health research continues to advance, the elucidation of these complex mechanisms will be crucial for disease control, prevention, and treatment. [ABSTRACT FROM AUTHOR]

Background and Aim: Helicobacter pylori (H. pylori) infection is a bacterial disease of the stomach that has been associated with an increased incidence of cholelithiasis. While the updated German guideline emphasizes the relevance of H. pylori as a pathogen and recommends eradication therapy, systematic data on the association between H. pylori infection, its eradication, and the subsequent diagnosis of cholelithiasis in Germany are missing. Methods: A total of 25 416 patients with and 25 416 propensity score‐matched individuals without H. pylori infection were identified from the Disease Analyzer database (IQVIA) between 2005 and 2021. A subsequent diagnosis of cholelithiasis was analyzed as a function of H. pylori infection as well as its eradication using Cox regression models. Results: After 10 years of follow‐up, 8.0% versus 5.8% of patients with and without H. pylori infection were diagnosed with cholelithiasis (P < 0.001). Regression analysis revealed a significant association between H. pylori infection and cholelithiasis (hazard ratio [HR]: 1.45; 95% confidence interval [CI]: 1.33–1.58), which was stronger in men (HR: 1.63; 95% CI: 1.41–1.90) than in women (HR: 1.36; 95% CI: 1.22–1.52). In terms of eradication therapy, both an eradicated H. pylori infection (HR: 1.48; 95% CI: 1.31–1.67) and a non‐eradicated H. pylori infection (HR: 1.41; 95% CI: 1.25–1.60) were associated with a subsequent diagnosis of cholelithiasis. Conclusion: The present study reveals a strong association between H. pylori infection and a subsequent diagnosis of cholelithiasis in a large real‐world cohort from Germany. Eradication therapy was not associated with a reduced incidence of cholelithiasis in our cohort. [ABSTRACT FROM AUTHOR]

Introduction: Recently, antibiotics use in uncomplicated acute diverticulitis (AD) has been controversial in Europe. The American Gastroenterological Association (AGA) in their 2015 guidelines recommend their selective use. Our study highlights their role in outpatient management. Methods: We queried the Diamond Network through TriNetX‐Research Network including 92 healthcare organizations. We included large intestine diverticulitis without perforation, abscess or bleeding. Exclusion criteria included any of sepsis criteria, CRP > 15 mg/L, immunodeficiency or HIV, coronary artery disease, chronic kidney disease, history of Crohn's disease or ulcerative colitis, heart failure, hypertension, diabetes or any of the following in the 3 months before study date; clostridium difficile (C. diff) infection, diverticulitis or antibiotics. Patients with AD were divided into two cohorts; patients on antibiotics, and patients not on antibiotics. Cohorts were compared after propensity‐score matching (PSM). Results: 214,277 patients met inclusion criteria. 58.9% received antibiotics, and 41% did not. After PSM, both cohorts had 84,320. Rate of hospital admission was lower in the antibiotic group (3.3% vs 4.2%, p <.001). There was a statistical difference between ICU admission (0.1% vs 0.15%, p <.01) and the rate of bowel perforation, peritonitis, abscess formation or bleeding (1.3% vs 1.4%, p =.044). There was no difference in mortality (0.1% vs 0.1%, p =.11), C. diff (0.1% vs 0.1%, p =.9), colectomies (0.2% vs 0.2%, p =.33), or Acute Kidney Injury (AKI) (0.1% vs 0.1%, p =.28). Conclusion: Outpatient use of antibiotics in patients with uncomplicated AD is associated with lower rates of hospital admissions and complications without changing mortality rate or surgical intervention. [ABSTRACT FROM AUTHOR]

Background: Older adults in nursing and care homes (NCHs) are vulnerable to severe respiratory syncytial virus (RSV) infection, hospitalization, and death. This study aimed to gather data on RSV disease among older adults in NCHs and identify reported risk factors for RSV hospitalization and case fatality. Methods: The study protocol was registered in PROSPERO (CRD42022371908). We searched MEDLINE, EMBASE, and Global Health databases to identify articles published between 2000 and 2023. Observational and experimental studies conducted among older adults in NCHs requiring assistive care and reporting RSV illness were included and relevant data were extracted. Results: Of 18,690 studies screened, 32 were selected for full‐text review, and 20 were included. Overall, the number of NCH residents ranged from 42 to 1459 with a mean age between 67.6 and 85 years. Attack rates ranged from 6.7% to 47.6% and annual incidence ranged from 0.5% to 14%. Case fatality rates ranged from 7.7% to 23.1%. We found similar annual incidence rates of RSV‐positive acute respiratory infection (ARI) of 4582 (95% CI: 3259–6264) and 4785 (95% CI: 2258–10,141) per 100,000 reported in two studies. Annual incidence rate of RSV‐positive lower respiratory tract infection was 3040 (95% CI: 1986–4454) cases per 100,000 adults. Annual RSV‐ARI hospital admission rates were between 600 (95% CI: 190–10,000) and 1104 (95% CI: 350–1930) per 100,000 person‐years. Among all RSV disease cases, commonly reported chronic medical conditions included chronic obstructive pulmonary disease (COPD), heart failure, ischemic heart disease, coronary artery disease, hypertension, diabetes, kidney dysfunction, cerebrovascular accident, malignancies, dementia, and those with a Charlson comorbidity score > 6.5. Conclusion: Data on RSV infection among NCH residents are limited and largely heterogeneous but document a high risk of illness, frequent hospitalization, and high mortality. Preventive interventions, such as vaccination, should be considered for this high‐risk population. Nationally representative epidemiologic studies and NCH‐based viral pathogen surveillance could more precisely assess the burden on NCH residents. [ABSTRACT FROM AUTHOR]

Objectives: Haematopoietic stem cell transplant (HCT) is a cellular therapy that, whilst curative for a child's underlying disease, carries significant risk of mortality, including because of pulmonary complications. The aims of this study were to describe the burden of pulmonary complications post‐HCT in a cohort of Australian children and identify risk factors for the development of these complications. Methods: Patients were identified from the HCT databases at two paediatric transplant centres in Australia. Medical records were reviewed, and demographics, HCT characteristics and pulmonary complications documented. Relative risk ratio was used to identify risk factors for developing pulmonary complications prior to first transplant episode, and survival analysis performed to determine hazard ratio. Results: In total, 243 children underwent transplant during the study period, and pulmonary complications occurred in 48% (117/243) of children. Infectious complications were more common (55%) than non‐infective complications (18%) and 26% of patients developed both. Risk factors for the development of pulmonary complications included the following: diagnoses of MPAL (RR 2.16, P = 0.02), matched unrelated donor (RR1.34, P = 0.03), peripheral blood (RR 1.36, P = 0.028) or cord blood (RR 1.73, P = 0.012) as the stem cell source and pre‐existing lung disease (RR1.72, P < 0.0001). Children with a post‐HCT lung complication had a significantly increased risk of mortality compared with those who did not (HR 3.9, P < 0.0001). Conclusion: This study demonstrates pulmonary complications continue to occur frequently in children post‐HCT and contribute significantly to mortality. Highlighting the need for improved strategies to identify patients at risk pre‐transplant and enhanced treatments for those who develop lung disease. [ABSTRACT FROM AUTHOR]

Chronic endometritis (CE) is a frequent pathological condition that is defined as localized inflammation in the endometrium. Some adverse fertility consequences such as recurrent miscarriage and failure of implantation are associated with chronic endometritis. On the one hand, inflammation plays an important role in the pathogenesis of endometritis, and on the other hand, the role of viral infections in inducing inflammation can make this review strongly attractive and practical. We set out to provide an overview of viral infections as a potential etiology of CE pathophysiology through the alteration of an endometrial microenvironment and its association with infertility. To the best of our knowledge, this is the first review to demonstrate the role of viral infection in chronic endometritis, and whether or not infection ultimately plays a role.. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Cervicofacial necrotizing fasciitis (CNF) can occur as a dental complication in young, healthy individuals. Early diagnosis, treatment, and awareness of severe acute cervicofacial pain, rapid swelling, and radiological gas formation are crucial. Broad molecular profiling is recommended for understanding the organisms involved in such infections in future research. [ABSTRACT FROM AUTHOR]

B‐cell Acute Lymphoblastic Leukemia (B‐ALL) is the most common pediatric cancer, arising most often in children aged 2–5 years. This distinctive age distribution hints at an association between B‐ALL development and disrupted immune system function during a susceptible period during childhood, possibly triggered by early exposure to infection. While cure rates for childhood B‐ALL surpass 90% in high‐income nations, survivors suffer from diminished quality of life due to the side effects of treatment. Consequently, understanding the origins and evolution of B‐ALL, and how to prevent this prevalent childhood cancer, is paramount to alleviate this substantial health burden. This article provides an overview of our current understanding of the etiology of childhood B‐ALL and explores how this knowledge can inform preventive strategies. [ABSTRACT FROM AUTHOR]