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Introduction: Emerging evidence indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected individuals are at an increased risk for co-infections. This retrospective study aims to expand the knowledge of associated factors of respiratory co-infection in SARS-CoV-2 positivity., Methodology: A retrospective study was conducted to recruit fifty-five patients with laboratory-confirmed SARS-CoV-2 positivity. We additionally tested 29 other respiratory pathogens using RT-PCR assay for the same specimens tested for laboratory-confirmed SARS-CoV-2. Both univariate and multivariate analysis were performed to identify independent factors for co-infection. Cox regression was conducted to detect the association between co-infection and viral load after controlling other related factors., Results: Among all the fifty-five COVID-19 patients, the rate of co-infection with at least one other respiratory pathogen was 76.4% (42/55). The rate of bacterial co-infections was 83.3% (35/42), among which Streptococcus pneumonia was the most common co-infection. Over 70% of neutrophils proportion (OR: 4.563; 95% CI: 1.116-18.648) was an independently associated factor for bacterial co-infection, whereas fever (OR: 4.506; 95% CI: 1.044-19.441) and chest tightness (OR: 0.106; 95% CI: 0.015-0.743) for viral co-infection. The strongest promotion of SARS-CoV-2 viral decreasing load was detected from co-infection of only viruses (HR: 4.039; 95% CI: 1.238-13.177), and the weakest was found from co-infection of only bacteria (HR: 2.909; 95% CI: 1.308-6.472)., Conclusions: Various co-infections variously promote SARS-CoV-2 viral decreasing load. Timely identification of co-infections aggressively contributes to COVID-19 patient management., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Xiaowen Hu, Feng Zhang, Jing Jia, Xueling Xin, Xiaoqi Dai, Liyan Dong, Zhaoguo Wang, Fachun Jiang.)

High mortality has been reported in severe cases of COVID-19. Emerging reports suggested that the severity is not only due to SARS-CoV-2 infection, but also due to coinfections by other pathogens exhibiting symptoms like COVID-19. During the COVID-19 pandemic, simultaneous respiratory coinfections with various viral (Retroviridae, Flaviviridae, Orthomyxoviridae, and Picoviridae) and bacterial (Mycobacteriaceae, Mycoplasmataceae, Enterobacteriaceae and Helicobacteraceae) families have been observed. These pathogens intensify disease severity by potentially augmenting SARSCoV-2 replication, inflammation, and modulation of signaling pathways. Coinfection emerges as a critical determinant of COVID-19 severity, principally instigated by heightened pro-inflammatory cytokine levels, as cytokine storm. Thereby, in co-infection scenario, the severity is also driven by the modulation of inflammatory signaling pathways by both pathogens possibly associated with interleukin, interferon, and cell death exacerbating the severity. In the current review, we attempt to understand the role of co- infections by other pathogens and their involvement in the severity of COVID-19., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Patients with cirrhosis and clinically significant portal hypertension are at high risk of developing bacterial infections (BIs) that are the most common trigger of acute decompensation and acute-on-chronic liver failure. Furthermore, after decompensation, the risk of developing BIs further increases in an ominous vicious circle. BIs may be subtle, and they should be ruled out in all patients at admission and in case of deterioration. Timely administration of adequate empirical antibiotics is the cornerstone of treatment. Herein, we reviewed current evidences about pathogenesis, clinical implications and management of BIs in patients with cirrhosis and portal hypertension., Competing Interests: Disclosure PA held a patent with Biovie, received advisory board fees from Biovie, Biomarin, and GenFit and speaking fees from Grifols, Kedrion, and Bhering. SP received consulting fees from Plasma Protein Therapeutics Association and speaking fees from Grifols and Medscape. SI has nothing to disclose regarding the work under consideration for publication. No specific funding supported this study. Authors’ contribution: S. Incicco, P. Angeli, and S. Piano reviewed the literature and drafted the article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cirrhosis is an immune dysfunction state, and as such, patients with cirrhosis are susceptible to bacterial, fungal, and viral infections. Because of infection, these patients have a propensity to develop multiorgan failure, which is associated with high mortality. Bacterial infections are the most prevalent type of infection in patients with cirrhosis, with the prevalence of bacterial infections in patients admitted for an acute decompensating event ranging from 24% to 29%. Together with invasive fungal infections, bacterial infections are the most severe. Multidrug-resistant organisms have been evolving at a rapid and alarming rate around the world, which presents enormous challenges. The development of effective measures for the prevention, early detection, and treatment of infections in patients with cirrhosis is challenging, given the rising incidence of infections in this patient population., Competing Interests: Declaration of interests SP reports grants from the Italian Ministry of Health, European Association for the Study of the Liver, and EU (paid to the institution), has consulted for the Plasma Protein Therapeutics Association and Boehringer Ingelheim, and has received honoraria for lectures from Grifols and Medscape. SP is a member of the Italian Ministry of Health Technical and Scientific Committee. KRR reports grants and contracts from BMS, Intercept, Mallinckrodt, BioVie, Sequana, Grifols, Exact Sciences, HCC-Target, NASH-Target, Merck, Camarus, B and D Instruments (paid to the institution) and has consulted for Spark Therapeutics, Novo Nordisk, Mallinckrodt, Genfit, BioVie, and Pfizer. KRR has also participated on data and safety monitoring boards or advisory boards for Novartis, AstraZeneca, Genkyotex, and HiTide. CB and SM declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Acute undifferentiated febrile illness (AUFI) is often undiagnosed in Thailand, resulting in delayed or ineffective treatment. We compared the demographic, exposure history, and clinical characteristics of AUFI patients with laboratory evidence of bacterial and nonbacterial pathogens. Patients aged 2-80 years presenting to 12 hospitals in Nakhon Phanom and Tak provinces were enrolled from April 2017 through May 2020. Interviews were conducted and blood, urine, and sputum were collected for culture as well as rapid diagnostic and molecular testing. A total of 1,263 patients tested positive for one or more bacterial, viral, or parasitic pathogens and were included in the analysis. Multivariable logistic regression was performed to compare factors associated with bacterial infections versus nonbacterial infections. Bacterial infections were more commonly identified in participants from Nakhon Phanom than Tak. Bacterial infections were independently associated with several factors including age ≥50 years (adjusted odds ratio [95% CI]): (4.18 [2.85-6.14]), contact with farm animals (1.82 [1.29-2.57]), antibiotic use within 72 hours of hospital presentation (2.37 [1.50-3.74]), jaundice (2.31 [1.15-4.63]), existing comorbidities (2.77 [1.93-3.96]), contact with febrile individuals (0.42 [0.31-0.57]), muscle pain (0.44 [0.31-0.64]), and rash (0.45 [0.29-0.70]). Bacterial infections were also associated with longer hospitalization (2.75 [2.08-3.64]) and lower odds of recovery at the time of discharge (0.14 [0.07-0.31]). Consideration of patient characteristics and signs/symptoms may help to inform targeted laboratory testing for suspected infectious etiologies. Understanding factors associated with bacterial and non-bacterial causes of AUFI may aid diagnosis and judicious use of antibiotics in resource-limited settings.

Purpose of Review: In this review, we explore the intriguing and evolving connections between bacterial extracellular membrane nanovesicles (BEMNs) and atherosclerosis development, highlighting the evidence on molecular mechanisms by which BEMNs can promote the athero-inflammatory process that is central to the progression of atherosclerosis., Recent Findings: Atherosclerosis is a chronic inflammatory disease primarily driven by metabolic and lifestyle factors; however, some studies have suggested that bacterial infections may contribute to the development of both atherogenesis and inflammation in atherosclerotic lesions. In particular, the participation of BEMNs in atherosclerosis pathogenesis has attracted special attention. We provide some general insights into how the immune system responds to potential threats such as BEMNs during the development of atherosclerosis. A comprehensive understanding of contribution of BEMNs to atherosclerosis pathogenesis may lead to the development of targeted interventions for the prevention and treatment of the disease., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Spontaneous bacterial peritonitis (SBP) represents a critical and potentially lethal condition that typically develops in individuals with liver cirrhosis. This meta-analysis aimed to assess diabetes mellitus (DM) as a risk factor for SBP in liver cirrhotic patients., Methods: Following PRISMA guidelines, fifteen studies were included, for a total of 76 815 patients. The risk of bias was assessed using the Newcastle-Ottawa scale (NOS). We represented the results as risk ratios (RR) with the corresponding 95% confidence intervals (CI) using RevMan software. Additionally, we pooled the hazard ratios (HR) for developing SBP in patients with DM from the included studies., Results: The meta-analysis shows a significantly increased risk of SBP in cirrhotic patients with DM (HR: 1.26; 95% CI [1.05-1.51], P =.01; HR: 1.70; 95% CI [1.32-2.18], P <.001)., Conclusions: The study signifies that DM is an independent risk factor for SBP, emphasizing the need for targeted preventive measures in this specific population.

Introduction: Clinical observations suggest that Omicron infections may present with different radiographic findings and be more frequently associated with bacterial co-infections, but there is a paucity of published data. This study aimed to compare the clinical and radiographic findings of patients hospitalized with Omicron versus alpha-delta infections., Materials and Methods: Between January 1, 2021 and June 30, 2021 (alpha and delta period) and between January 1, 2022 and July 31, 2022 (Omicron period), respectively 149 and 163 COVID-19 PCR-positive patients who were followed up in the COVID-19 ward and intensive care unit of a tertiary care center were included in the study. Clinical (presence of fever and purulent sputum), laboratory and radiologic findings of the two groups were compared. Sputum culture results and antibiotic use were also evaluated., Result: In the alpha/delta group, ground glass opacities were seen in 75.2% (112) of the patients, consolidation in 2.7% (4), and both findings together in 6.0% (9). In the Omicron group, ground glass was seen in 40.5% (66), consolidation in 5.5% (9), and both ground glass and consolidation together in 8.7% (13) (p< 0.001). Procalcitonin levels were 0.25 µg/L or higher in 29.6% and 43.9% of the patients in the alpha/delta and Omicron groups, respectively. Mean PCT values were 0.36 µg/L and 1.93 µg/L, respectively (p> 0.05). CRP levels were similar in both groups. Mean LDH level in the Omicron group was 278 U/L and was significantly lower than the alpha/delta group (381 U/L) (p< 0.001). The proportion of patients requiring intensive care during hospitalization was higher in the alpha/delta group (36.2% vs 26.4%) (p= 0.06)., Conclusions: Lower LDH levels, less need for intensive care and less frequent development of ARDS indicate that Omicron causes milder disease, while a higher rate of consolidation and higher procalcitonin levels suggest a higher frequency of bacterial co-infections.

Background: An increasing number of research indicates an association between low-grade bacterial infections, particularly those caused by Propionibacterium acnes (P. acnes), and the development of intervertebral disc degeneration (IDD). However, no previous meta-analysis has systematically assessed the risk factors for low-grade bacterial infections that cause IDD., Purpose: This study reviewed the literature to evaluate the risk factors associated with low-grade bacterial infection in patients with IDD., Study Design: Systematic review and meta-analysis., Methods: The systematic literature review was conducted using the PubMed, Web of Science, Embase, and Cochrane Library databases. Eligible articles explicitly identified the risk factors for low-grade bacterial infections in IDD patients. Patient demographics and total bacterial infection rates were extracted from each study. Meta-analysis was performed using random- or fixed-effects models, with statistical analyses conducted using Review Manager (RevMan) 5.4 software.aut., Results: Thirty-three studies involving 4,109 patients were included in the meta-analysis. The overall pooled low-grade bacterial infection rate was 30% (range, 24%-37%), with P. acnes accounting for 25% (range, 19%-31%). P. acnes constituted 66.7% of bacteria-positive discs. Fourteen risk factors were identified, of which 8 were quantitatively explored. Strong evidence supported male sex (odds ratio [OR] = 2.15; 95% confidence interval [CI]=1.65-2.79; p<.00001) and Modic changes (MCs) (OR=3.59; 95% CI=1.68-7.76; p=.0009); moderate evidence of sciatica (OR=2.31; 95% CI=1.33-4.00; p=.003) and younger age (OR=-3.47; 95% CI=-6.42 to -0.53; p=.02). No evidence supported previous disc surgery, MC type, Pfirrmann grade, smoking, or diabetes being risk factors for low-grade bacterial infections in patients with IDD., Conclusions: Current evidence highlights a significant association between IDD and low-grade bacterial infections, predominantly P. acnes being the most common causative agent. Risk factors associated with low-grade bacterial infections in IDD include male sex, MCs, sciatica, and younger age., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

End-stage liver disease (ESLD) is a life-threatening clinical syndrome and when complicated with infection the mortality is markedly increased. In patients with ESLD, bacterial or fungal infection can induce or aggravate the occurrence or progression of liver decompensation. Consequently, infections are among the most common complications of disease deterioration. There is an overwhelming need for standardized protocols for early diagnosis and appropriate management for patients with ESLD complicated by infections. Asia Pacific region has the largest number of ESLD patients, due to hepatitis B and the growing population of alcohol and NAFLD. Concomitant infections not only add to organ failure and high mortality but also to financial and healthcare burdens. This consensus document assembled up-to-date knowledge and experience from colleagues across the Asia-Pacific region, providing data on the principles as well as evidence-based current working protocols and practices for the diagnosis and treatment of patients with ESLD complicated by infections., (© 2024. Asian Pacific Association for the Study of the Liver.)

Adrenomedullin (ADM) is a peptide hormone produced primarily in the adrenal glands, playing a crucial role in various physiological processes. As well as improving vascular integrity and decreasing vascular permeability, ADM acts as a vasodilator, positive inotrope, diuretic, natriuretic and bronchodilator, antagonizing angiotensin II by inhibiting aldosterone secretion. ADM also has antihypertrophic, anti-apoptotic, antifibrotic, antioxidant, angiogenic and immunoregulatory effects and antimicrobial properties. ADM expression is upregulated by hypoxia, inflammation-inducing cytokines, viral or bacterial substances, strength of shear stress, and leakage of blood vessels. These pathological conditions are established during systemic inflammation that can result from infections, surgery, trauma/accidents or burns. The ability to rapidly identify infections and the prognostic, predictive power makes it a valuable tool in severe viral and bacterial infections burdened by high incidence and mortality. This review sheds light on the pathophysiological processes that in severe viral or bacterial infections cause endothelitis up to the development of organ damage, the resulting increase in ADM levels dosed through its more stable peptide mid-regional proadrenomedullin (MR-proADM), the most significant studies that attest to its diagnostic and prognostic accuracy in highlighting the severity of viral or bacterial infections and appropriate therapeutic insights.

Introduction: Febrile young infants are at risk of serious bacterial infections (SBIs), which are potentially life-threatening. This study aims to investigate the association between delayed presentation and the risk of SBIs among febrile infants., Method: We performed a prospective cohort study on febrile infants ≤90 days old presenting to a Singapore paediatric emergency department (ED) between November 2017 and July 2022. We defined delayed presentation as presentation to the ED >24 hours from fever onset. We compared the proportion of SBIs in infants who had delayed presentation compared to those without, and their clinical outcomes. We also performed a multivariable logistic regression to study if delayed presentation was independently associated with the presence of SBIs., Results: Among 1911 febrile infants analysed, 198 infants (10%) had delayed presentation. Febrile infants with delayed presentation were more likely to have SBIs (28.8% versus [vs] 16.3%, P<0.001). A higher proportion of infants with delayed presentation required intravenous antibiotics (64.1% vs 51.9%, P=0.001). After adjusting for age, sex and severity index score, delayed presentation was independently associated with the presence of SBI (adjusted odds ratio [AOR] 1.78, 95% confidence interval 1.26-2.52, P<0.001)., Conclusion: Febrile infants with delayed presentation are at higher risk of SBI. Frontline clinicians should take this into account when assessing febrile infants., Competing Interests: The authors have no conflict of interest to declare.

Background and Aims: Infection is a serious complication in patients with cirrhosis. Mucosal-associated invariant T (MAIT) cells are involved in the immune defense against infections and known to be impaired in several chronic conditions, including cirrhosis. Here, we evaluated if MAIT cell levels in peripheral blood are associated with risk of bacterial infections in patients with cirrhosis., Methods: Patients with cirrhosis seen at the Karolinska University Hospital, Stockholm, Sweden, between 2016 and 2019 were included. Levels of MAIT cells in peripheral blood were determined using flow cytometry. Baseline and follow-up data after at least two years of follow-up were collected by chart review for the primary outcome (bacterial infection) and secondary outcomes (decompensation and death). Competing risk and Cox regression were performed., Results: We included 106 patients with cirrhosis. The median MAIT cells fraction in the circulation was 0.8% in cirrhosis compared to 6.1% in healthy controls. In contrast to our hypothesis, we found an association in the adjusted analysis between relatively preserved MAIT cell levels, and a slightly higher risk to develop bacterial infections (adjusted subdistribution hazard ratio (aSHR) 1.15 (95%CI = 1.01-1.31). However, MAIT cell levels were not associated with the risk of hepatic decompensation (aSHR 1.19 (95%CI = 0.91-1.56)) nor with death (adjusted hazard ratio 1.10 (95%CI = 0.97-1.22))., Conclusions: Relatively preserved MAIT cell levels in blood of patients with cirrhosis were associated with a somewhat higher risk of bacterial infections. The clinical relevance of this might not be strong. MAIT cells might however be an interesting biomarker to explore in future studies., Competing Interests: HH reports research funding to his institution from Astra Zeneca, EchoSens, Gilead, Intercept, MSD, Novo Nordisk and Pfizer. Board advisory for BMS. All outside the current work. BB, CM, JKS, and NKB report no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Bengtsson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Enterococcus is a relatively uncommon pathogen that causes urinary tract infections (UTIs) in healthy children. Most enterococcal infections occur in patients with risk factors such as anatomical or functional urinary tract anomalies, also known as CAKUT (congenital anomalies of kidney and urinary tract). Children who are suspected of having UTIs and who have certain risk factors are often treated specifically for enterococcal infection as part of their empiric regimen. Our primary objective was to determine the prevalence of enterococcal UTIs among high-risk children, and specifically among those with positive nitrite tests, with the goal of avoiding treatment with specific anti-enterococcal agents. This retrospective study included all the episodes of UTI treated at a tertiary pediatric center during 2010 to 2018. The data collected from medical records included nephrological and urological risk factors, nitrite status, and isolated pathogens. Of 931 episodes of UTI, 467 (50%) were considered high-risk. In all, 24 of the latter had Enterococcus as a single pathogen; 23 (96%) of these occurred in patients with negative nitrites in the first urine dipstick taken. The sole patient with high-risk factors, a positive nitrite test and coexisting enterococcal UTI had a history of previous enterococcal UTIs. In pediatric patients with nephrological and urological risk factors, who have positive nitrites in urinalysis, the risk for enterococcal UTI appears substantially low. Therefore, in this context, specific anti-enterococcal empirical antibiotic therapy may be unnecessary., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Prostatitis is a major urological disease affecting 25%-50% of men over their lifetime. However, prostatitis is often overlooked in nonurologic departments due to its sometimes indeterminate symptoms. In this review, we describe how to recognize and treat acute bacterial prostatitis, which manifests as a clinical problem in other departments as well as urology, to help prevent this disease from being overlooked. There are several possible negative effects of not recognizing acute bacterial prostatitis (ABP). First, initial treatment can fail. In the hyperacute phase, common antibiotics are often effective, but in rare cases, such antibiotics may not be effective. In addition, once ABP progresses to form a prostate abscess, potentially avoidable surgical interventions are often needed. A second issue is the transition to chronic prostatitis. If chronic bacterial prostatitis progresses, treatment requires long-term antibiotic administration and the response rate is not high. Some patients may have to deal with urinary tract infections for the rest of their lives. Finally, there is the problem of overlooking the underlying disease. ABP is rare in healthy adult men without underlying disease, including sexually transmitted diseases as well as benign prostatic hyperplasia, urinary stones, and malignant tumors, and may not be obvious. When examining patients with fever of unknown origin, it is necessary to exclude not only infectious diseases but also collagen diseases and malignant tumors. If there are any doubts, we recommend a rectal exam and consultation with a urologist., (© 2024 The Japanese Urological Association.)

In this multicenter, cross-sectional, secondary analysis of 4042 low-risk febrile infants, nearly 10% had a contaminated culture obtained during their evaluation (4.9% of blood cultures, 5.0% of urine cultures, and 1.8% of cerebrospinal fluid cultures). Our findings have important implications for improving sterile technique and reducing unnecessary cultures., Competing Interests: Declaration of Competing Interest Colleen K. Gutman was supported by NIH/NCATS grant number KL2TR001429. Paul L. Aronson is supported by NIH/NICHD grant number R03 HD110741. The NIH had no role in the design and conduct of the study. The other authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The use of a single C-reactive protein (CRP) value to differentiate between bacterial and non-bacterial causes is limited. Estimated CRP velocity (eCRPv) has shown promise in enhancing such discrimination in adults. This study aims to investigate the association between eCRPv and bacterial etiologies among pediatric patients with very elevated CRP levels. We conducted a retrospective analysis of patients under 18 years of age who had been admitted to our Pediatric Emergency Department from 2018 to 2020 with a fever and CRP levels ≥ 150 mg/L. Bacterial and non-bacterial etiologies were determined from hospital discharge diagnoses, which were monitored independently by three physicians from the research team. The records of 495 suitable patients (51.2% males, median age 3.2 years) were retrieved of whom 444 (89.7%) were eventually diagnosed with bacterial infections. The mean CRP levels were significantly higher for bacterial etiologies compared with other causes (209.2 ± 59.8 mg/L vs. 185.6 ± 35.8 mg/L, respectively, p < .001), while the mean eCRPv values did not differ significantly (p = .15). In a time course analysis, we found that specifically in patients presenting ≥ 72 h after symptom onset, only a eCRPv1 level > 1.08 mg/L/h was an independent predictor of bacterial infection (aOR = 5.5 [95% CI 1.7-17.8], p = .004).   Conclusion: Pediatric patients with very high CRP levels and fever mostly have bacterial infections. eCRPv levels, unlike CRP values alone, can serve as the sole independent predictor of bacterial infection > 72 h from symptom onset, warranting further prospective investigations into CRP kinetics in pediatric patients. What is Known: • The use of a single C-reactive protein (CRP) value to differentiate between bacterial and non-bacterial causes is limited. • Estimated CRP velocity (eCRPv) has shown promise in enhancing such discrimination in adults, but data on CRP kinetics in pediatric patients is sparse. What is New: • eCRPv levels, unlike CRP values alone, can serve as the sole independent predictor of bacterial infection > 72 h from symptom onset in pediatric patients with remarkably elevated CRP levels., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The pathogenesis involved in glucose metabolism disorders (GMDs) in patients with liver cirrhosis remains unclear., Aims: We investigated the effects of acute-on-chronic liver failure (ACLF) development and bacterial infections (BIs) on pancreatic β-cell function and glucose homeostasis in individuals with liver cirrhosis., Methods: A retrospective analysis was conducted on 327 patients experiencing acute deterioration of liver cirrhosis. Oral glucose tolerance tests (OGTTs) and OGTT-based β-cell function indices were employed to assess β-cell function and glucose homeostasis. Univariate and multivariate logistic regression analyses were employed to identify GMD-associated risk factors., Results: Both the development of ACLF and BIs significantly increased the prevalence of GMDs. Both ACLF and BIs markedly elevated the homeostasis model of assessment 2-insulin resistance (HOMA2-IR). ACLF significantly impaired glucose-stimulated insulin secretion, as evidenced by reduced insulinogenic index (IGI). Patients with GMDs exhibited significantly lower IGI levels than those without GMDs. Independent risk factors associated with GMDs were prothrombin activity (odds ratio [OR]=0.981, 95% confidence interval [CI]: 0.960-0.995), HOMA2-IR (OR=1.749, 95% CI: 1.130-2.707), and IGI (OR=0.963, 95% CI: 0.947-0.978)., Conclusions: In liver cirrhosis, the onset of ACLF impairs glucose-stimulated insulin secretion from β-cells. Both liver impairment and BIs contribute to increased insulin resistance, ultimately disturbing glucose homeostasis., Competing Interests: Conflict of interest Yujuan Liu, Han Hu, Chuan Li, Yin Zhang, Meichuan Li, Tao Lu, Yunchong Wu, Yanyan Yang, Ying Li, Fangwan Yang, Xiuquan Shi, and Shide Lin declare no competing interests., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Small intestine bacterial overgrowth (SIBO) has been associated with enteric inflammation, linear growth stunting, and neurodevelopmental delays in children from low-income countries. Little is known about the histologic changes or epithelial adherent microbiota associated with SIBO. We sought to describe these relationships in a cohort of impoverished Bangladeshi children. Undernourished 12-18-month-old children underwent both glucose hydrogen breath testing for SIBO and duodenoscopy with biopsy. Biopsy samples were subject to both histological scoring and 16s rRNA sequencing. 118 children were enrolled with 16s sequencing data available on 53. Of 11 histological features, we found that SIBO was associated with one, enterocyte injury in the second part of the duodenum (R = 0.21, p = 0.02). SIBO was also associated with a significant increase in Campylobacter by 16s rRNA analysis (Log 2-fold change of 4.43; adjusted p = 1.9 x 10-6). These findings support the growing body of literature showing an association between SIBO and enteric inflammation and enterocyte injury and further delineate the subgroup of children with environmental enteric dysfunction who have SIBO. Further, they show a novel association between SIBO and Campylobacter. Mechanistic work is needed to understand the relationship between SIBO, enterocyte injury, and Campylobacter., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fahim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Infectious Keratitis is one of the most common ocular emergencies seen by ophthalmologists. Our aim is to identify the risk factors and clinical features of Acanthamoeba Keratitis (AK)., Methods: This retrospective chart review study was conducted at King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia, and included all the microbial keratitis cases, male and female patients of all ages. The main outcome is the differentiation between various microbial keratitis types., Results: We included 134 consecutive eyes of 126 persons. We had 24 cases of acanthamoeba keratitis, 22 bacterial keratitis, 24 fungal keratitis, 32 herpetic keratitis, and 32 bacterial co-infection. Contact lens wear was found in 33 eyes (24.6%). Among acanthamoeba keratitis patients, 73% were ≤ 39 years of age, and 73% were females (P <0.001). Also, in AK cases, epithelial defect was found in all cases (100%), endothelial plaques were found in 18 eyes (69.2%), 12 cases had radial keratoneuritis (46.2%), and ring infiltrate was found in 53.8% of AK cases., Conclusions: We determined the factors that increase the risk of acanthamoeba infection and the clinical characteristics that help distinguish it from other types of microbial keratitis. Our findings suggest that younger females and patients who wear contact lenses are more likely to develop acanthamoeba keratitis. The occurrence of epitheliopathy, ring infiltrate, radial keratoneuritis, and endothelial plaques indicate the possibility of acanthamoeba infection. Promoting education on wearing contact lenses is essential to reduce the risk of acanthamoeba infection, as it is the most significant risk factor for this infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Alreshidi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The relationship between ammonia and liver-related complications (LRCs) in acute-on-chronic liver failure (ACLF) patients is not clearly established. This study aimed to evaluate the association between ammonia levels and LRCs in patients with ACLF. The study also evaluated the ability of ammonia in predicting mortality and progression of LRCs. The study prospectively recruited ACLF patients based on the APASL definition from the ACLF Research Consortium (AARC) from 2009 to 2019. LRCs were a composite endpoint of bacterial infection, overt hepatic encephalopathy (HE), and ascites. A total of 3871 cases were screened. Of these, 701 ACLF patients were enrolled. Patients with LRCs had significantly higher ammonia levels than those without. Ammonia was significantly higher in patients with overt HE and ascites, but not in those with bacterial infection. Multivariate analysis found that ammonia was associated with LRCs. Additionally, baseline arterial ammonia was an independent predictor of 30-day mortality, but it was not associated with the development of new LRCs within 30 days. In summary, baseline arterial ammonia levels are associated with 30-day mortality and LRCs, mainly overt HE and ascites in ACLF patients., (© 2024. The Author(s).)

Background: As a common complication of viral respiratory tract infection, bacterial infection was associated with higher mortality and morbidity. Determining the prevalence, culprit pathogens, outcomes, and risk factors of co-infection and secondary infection occurring in hospitalized patients with coronavirus disease 2019 (COVID-19) will be beneficial for better antibiotic management., Methods: In this retrospective cohort research, we assessed clinical characteristics, laboratory parameters, microbiologic results, and outcomes of laboratory-confirmed COVID-19 patients with bacterial co-infection and secondary infection in West China Hospital from 2022 December 2nd to 2023 March 15th., Results: The incidence of bacterial co-infection and secondary infection, as defined by positive culture results of clinical specimens, was 16.3% (178/1091) and 10.1% (110/1091) respectively among 1091 patients. Acinetobacter, Klebsiella, and Pseudomonas were the most commonly identified bacteria in respiratory tract samples of COVID-19 patients. In-hospital mortality of COVID-19 patients with co-infection (17.4% vs 9.5%, p = 0.003) and secondary infection (28.2% vs 9.5%, p < 0.001) greatly exceeded that of COVID-19 patients without bacterial infection. Cardiovascular disease (1.847 (1.202-2.837), p = 0.005), severe COVID-19 (1.694 (1.033-2.778), p = 0.037), and critical COVID-19 (2.220 (1.196-4.121), p = 0.012) were proved to be risk factors for bacterial co-infection, while only critical COVID-19 (1.847 (1.202-2.837), p = 0.005) was closely related to secondary infection., Conclusions: Bacterial co-infection and secondary infection could aggravate the disease severity and worsen clinical outcomes of COVID-19 patients. Notably, only critical COVID-19 subtype was proved to be an independent risk factor for both co-infection and secondary infection. Therefore, standard empirical antibiotics was recommended for critically ill COVID-19 rather than all the inpatients according to our research., (© 2024. The Author(s).)

Background: Portal vein thrombosis (PVT) and sepsis are common complications in patients with liver cirrhosis. Factors that lead to PVT are not completely understood. This study aimed to investigate the possible association between bacterial infections and the development of PVT in cirrhotic patients., Patients and Methods: 202 consecutive cirrhotic patients without previous infections, followed at the Liver Unit in Verona Hospital, were enrolled from 2017 to 2021 (median follow-up 3.3 years). During the follow-up period, PVT was diagnosed by ultrasound, CT and/or MRI, and episodes of bacterial infections requiring hospitalization were recorded. Malignant PVT was an exclusion criterion., Results: Of the 202 patients enrolled (68.3 % males, mean age 63.8 ± 11 years), 22 (10.8 %) developed PVT during the follow up. In patients with PVT, the prevalence of previous bacterial infections was significantly higher compared to patients without PVT (63.6% vs 31.1 %; p = 0.02). Cox regression analysis revealed that a history of bacterial infection was the only variable that demonstrated a significant association with the risk of de novo PVT occurrence (HR 4.04, 95 % CI: 1.68-9.65)., Conclusion: in patients with liver cirrhosis bacterial infections are a predisposing factor for the following development of PVT. Further studies are needed to confirm this evidence., Competing Interests: Conflict of interest The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Diabetes mellitus is associated with a wide range of neuropathies, vasculopathies, and immunopathies, resulting in many complications. More than 30% of diabetic patients risk developing diabetic foot ulcers (DFUs). Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play essential roles in various biological functions in the hyperglycaemic environment that determines the development of DFU. Ulceration results in tissue breakdown and skin barrier scavenging, thereby facilitating bacterial infection and biofilm formation. Many bacteria contribute to diabetic foot infection (DFI), including Staphylococcus aureus (S. aureus) et al. A heterogeneous group of "ncRNAs," termed small RNAs (sRNAs), powerfully regulates biofilm formation and DFI healing. Multidisciplinary foot care interventions have been identified for nonhealing ulcers. With an appreciation of the link between disease processes and ncRNAs, a novel therapeutic model of bioactive materials loaded with ncRNAs has been developed to prevent and manage diabetic foot complications., (© 2023 John Wiley & Sons Ltd.)

Background: Patients with atopic dermatitis (AD), particularly infants and young children, are at greater risk of developing skin infections. In this study, we assessed infection rates in AD patients aged 6 months to 5 years treated with dupilumab., Methods: In LIBERTY AD PRESCHOOL, a double-blind, placebo-controlled, phase III clinical trial, children aged 6 months to 5 years with moderate-to-severe AD were randomized 1:1 to subcutaneous dupilumab or placebo, with concomitant low-potency topical corticosteroids, every 4 weeks for 16 weeks. Exposure-adjusted infection rates were used to compare treatment groups., Results: The analysis included 162 patients, of whom 83 received dupilumab and 79 received placebo. Total infection rates were not significantly different between the dupilumab and placebo groups (rate ratio [RR] 0.75, 95% CI 0.48-1.19; p = 0.223). Non-herpetic adjudicated skin infections and bacterial infections were significantly less frequent with dupilumab versus placebo (non-herpetic skin infections: RR 0.46, 95% CI 0.21-0.99; p = 0.047; bacterial infections: RR 0.09, 95% CI 0.01-0.67; p = 0.019), and the number of patients using systemic anti-infective medication was significantly lower in the dupilumab group (RR 0.52, 95% CI 0.30-0.89; p = 0.019). There were no significant differences in the number of herpetic infections between the dupilumab and placebo groups (RR 1.17, 95% CI 0.31-4.35; p = 0.817). The number of patients with two or more infection events was significantly higher in the placebo group (RR 0.29, 95% CI 0.12-0.68; p = 0.004), and no severe or serious infections (including eczema herpeticum) were observed among patients receiving dupilumab., Conclusions: These data suggest that dupilumab treatment in infants and children younger than 6 years with AD does not increase overall risk of infections and is associated with a reduced risk of bacterial and non-herpetic skin infections compared with placebo, resulting in a reduced need for anti-infective medication., Trial Registration: The trial was registered with ClinicalTrials.gov with ID number NCT03346434 on November 17, 2017. INFOGRAPHIC., (© 2024. The Author(s).)

Background: Viral infection is a risk factor for asthma exacerbation (AE). However, bacterial infections related to AE in adults are poorly known. On the other hand, obese patients with asthma have their own clinical and biological characteristics compared with non-obese patients., Methods: We investigated the differences in isolated pathogens for AE between obese and non-obese patients with asthma. We included 407 patients with AE from 24 medical centers in Korea. Microorganisms isolated from culture, RT-PCR or serologic tests using lower respiratory tract specimens were retrospectively investigated., Results: A total of 171 obese and 236 non-obese patients with asthma were included for analysis. Compared to non-obese patients, obese patients were associated with women (77.2% vs. 63.6%), never smoker (82.5% vs. 73.9%), shorter duration of asthma (7.9 ± 8.4 vs. 10.5 ± 10.1 years), less history of pulmonary tuberculosis (8.8% vs. 17.4%), and more comorbidity of allergic rhinitis (48.5% vs. 0.8%). Viral and/or bacterial infections were detected in 205 patients (50.4%) with AE. The numbers of patients with viral only, bacterial only, or both infections were 119, 49, and 37, respectively. The most commonly isolated bacterium was Streptococcus pneumoniae, followed by Pseudomonas aeruginosa and Chlamydia pneumoniae. Obese patients showed a lower incidence of Chlamydia pneumoniae infection. In the non-obese group, bacterial infection, especially Chlamydia pneumoniae infection, was significantly associated with the duration of systemic corticosteroid use (13.6 ± 19.8 vs. 9.7 ± 6.7 days, p = 0.049)., Conclusion: Bacterial infection was associated with a longer period of corticosteroid use in the non-obese group. Acute Chlamydia pneumoniae infection was less associated with obese patients with AE. Further well-designed studies are needed to evaluate microorganisms and the efficacy of antibiotics in patients with AE., (© 2024. The Author(s).)

Emergency clinicians frequently provide care to febrile infants aged ≤60 days in the emergency department. In these very young infants, fever may be the only presenting sign of invasive bacterial infection and, if untreated, invasive bacterial infection can lead to severe outcomes. This issue reviews newer risk-stratification tools and the 2021 American Academy of Pediatrics clinical practice guideline to provide recommendations for the evaluation and management of febrile young infants. The most recent literature assessing the risk of concomitant invasive bacterial infection with urinary tract infections or positive viral testing is also reviewed., (Copyright 2024 EB Medicine.)

Objective: The purpose was to look into the diagnostic value of serum CRP, PCT and IL-6 in children with nephrotic syndrome co-infection., Methods: One hundred and forty-nine children with nephrotic syndrome who met the inclusion and exclusion criteria were included in this study. The children were divided into three groups: bacterial infection group, non-bacterial infection group, and non-infection group. The diagnostic value was analyzed and compared using the ROC curve., Results: There was no statistically significant difference in the Leukocyte counts among three groups. The mean results of serum CRP, PCT and IL-6 were significantly higher in the bacterial infection group compared to those in the non-infection group (p < 0.05). AUC of CRP, PCT, IL-6 in bacterial infection were 0.791, 0.859, 0.783. The following combinations CRP + PCT + IL-6, IL-6 + PCT, CRP + PCT significantly increased the efficiency of bacterial infection diagnosis, the AUCs were 0.881, 0.884, and 0.884, respectively. AUC of PCT in non-bacterial infection was 0.663. The combinations of these three clinical indicators performed no better than PCT in ROC analysis., Conclusion: Normal CRP or IL-6 levels do not rule out the diagnosis of bacterial infection in children on long-term glucocorticoid therapy. The appropriate combination of two or three indicators can improve the diagnostic value., Impact: This study evaluated the diagnostic value of the serum concentrations of CRP, PCT and IL-6 and assessed whether the value of their combined application is better than when used alone for diagnosing primary nephrotic syndrome complicated by infection. The elevation in leukocyte count cannot be used to diagnose children with nephrotic syndromes on long-term glucocorticoid treatment who have bacterial infections. Normal CRP or IL-6 levels do not rule out the diagnosis of bacterial infection in children on long-term glucocorticoid therapy. The appropriate combination of two or three indicators can improve diagnostic value, sensitivity, and specificity., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

While viruses are considered the most common infectious triggers for cytokine storm syndromes (CSS), a growing list of bacterial pathogens, particularly intracellular organisms, have been frequently reported to be associated with this syndrome. Both familial and sporadic cases of CSS are often precipitated by acute infections. It is also important to note that an underlying precipitating infection might not be clinically obvious as the CSS clinical picture can mimic an infectious process or an overwhelming septicemia. It is important to detect such an underlying treatable condition. In addition, infections can also be acquired during the course of CSS due to the concurrent immune suppression with treatment. Optimal CSS outcomes require treating bacterial infections when recognized.CSS should always be suspected in patients presenting with a sepsis-like or multi-organ dysfunction picture. There are many criteria proposed to diagnose CSS in general, with HLH-2004 being the most commonly used. Alternatively, criteria have been proposed for CSS occurring in specific underlying conditions such as systemic lupus erythematosus (SLE) or systemic juvenile idiopathic arthritis (sJIA). However, waiting for many of these criteria to be fulfilled could lead to significant delay in diagnosis, and the physician needs a high index of suspicion for CSS in critically ill febrile hospitalized patients in order to properly recognize the condition. Thus, there should be diagnostic equipoise between CSS and infections, including bacterial, in this population. In this chapter, we discuss the more common bacterial precipitants of CSS with many of the cases being discussed in the pediatric age group., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Introduction: Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel biomarker for liver fibrosis, but little is known about its role in cirrhosis-associated clinical outcomes. This study aimed to investigate the predictive role of M2BPGi in cirrhosis-associated complications., Methods: One hundred and forty-nine cirrhotic patients were retrospectively enrolled. Patients were followed up for 1 year, and cirrhosis-associated clinical events were recorded. Receiver operating characteristic curve (ROC) analysis was used to establish the values of the predictive models for cirrhotic outcomes, and Cox proportional hazards regression models were used to identify predictors of clinical outcomes., Results: Sixty (40.3%) patients experienced cirrhosis-associated clinical events and had higher M2BPGi levels compared to those without events (8.7 vs. 5.1 cutoff index, p &lt; 0.001). The most common cirrhosis-associated complications were bacterial infections (24.2%). On ROC analysis, M2BPGi to albumin ratio (M2BPGi/albumin) had comparable discriminant abilities for all cirrhosis-associated events (area under the ROC curve [AUC] = 0.74) compared with M2BPGi, Child-Pugh, model for end-stage liver disease, albumin-bilirubin scores, and neutrophil-to-lymphocyte ratio and was superior to M2BPGi alone for all bacterial infectious events (AUC = 0.80). Cox regression analysis revealed that the M2BPGi/albumin, but not M2BPGi alone, independently predicted all cirrhosis-associated events (hazard ratio [HR] = 1.34, p = 0.038) and all bacterial infectious events (HR = 1.51, p = 0.011) within 1 year. However, M2BPGi/albumin did not predict other cirrhotic complications and transplant-free survival., Discussion/conclusion: M2BPGi/albumin might serve as a potential prognostic indicator for patients with cirrhosis, particularly for predicting bacterial infections., (© 2024 S. Karger AG, Basel.)

Background: Neonatal bacterial infections have long been recognized as an important cause of acute morbidity and mortality, but long-term neurodevelopmental consequences have not been comprehensively described and discussed., Objectives: We aimed to summarize evidence on the pathogenesis, diagnosis, and epidemiology of long-term sequelae after neonatal bacterial sepsis and meningitis. We also discuss approaches for future studies to quantify the public health impact of neonatal infection-associated neurodevelopmental impairment., Sources: We identified studies, both research articles and reviews, which provide mechanistic information on the long-term disease, as well as epidemiological studies that describe the frequency of neurodevelopmental impairment in children with and, for comparison, without a history of neonatal bacterial infection. Tools currently used in clinical practice and research settings to assess neurodevelopmental impairment were also reviewed., Content: We first enumerate potential direct and indirect mechanisms that can lead to brain injury following neonatal infections. We then discuss summary data, either frequencies or measures of association, from epidemiological studies. Risk factors that predict long-term outcomes are also described. Finally, we describe clinical approaches for identifying children with neurodevelopmental impairment and provide an overview of common diagnostic tools., Implications: The limited number of studies that describe the long-term consequences of neonatal infections, often undertaken in high-income settings and using variable designs and diagnostic tools, are not sufficient to inform clinical practice and policy prioritization. Multi-country studies with follow-up into adolescence, standardized diagnostic approaches, and local comparator groups are needed, especially in low and middle-income countries where the incidence of neonatal sepsis is high., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Acute cholangitis is an ominous complication in biliary atresia (BA) patients. We investigated the prevalence of small intestine bacterial overgrowth (SIBO) in BA patients and its role in predicting acute cholangitis., Methods: There are 69 BA patients with native liver recruited into this study prospectively. They received hydrogen and methane-based breath testing (HMBT) to detect SIBO after recruitment and were followed prospectively in our institute., Results: There are 16 (23.19%) subjects detected to have SIBO by HMBT. BA subjects with SIBO were noted to have higher serum alanine aminotransferase levels than others without SIBO (P = 0.03). The risk of acute cholangitis is significantly higher in BA patients with SIBO than in others without SIBO (62.50% vs. 15.09%, P < 0.001). The logistic regression analysis demonstrated that BA subjects with SIBO have a higher risk of acute cholangitis than others without SIBO (odds ratio = 9.38, P = 0.001). Cox's proportional hazard analysis further confirmed the phenomena in survival analysis (hazard ratio = 6.43, P < 0.001)., Conclusions: The prevalence of SIBO in BA patients is 23.19% in this study. The presence of SIBO is associated with the occurrence of acute cholangitis in BA patients., Impact: What is the key message of your article? Acute cholangitis is common in BA, and is associated with SIBO after hepatoportoenterostomy in this study. What does it add to the existing literature? This study demonstrated that SIBO is common in BA after hepatoportoenterostomy, and is predictive of acute cholangitis and elevated serum ALT levels in BA. What is the impact? This prospective cohort study provides data regarding the significance of SIBO on the risk of acute cholangitis in BA patients., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

We aimed to assess the prevalence of serious bacterial infections (SBIs) in febrile infants < 90 days of age with SARS-CoV-2 infection versus SARS-CoV-2-negative febrile infants. A retrospective cohort study was conducted in a tertiary pediatric emergency department between March 2020 and October 2022. Febrile infants < 90 days of age who underwent SARS-CoV-2 testing were included. SBIs were defined as urinary tract infection (UTI), bacteremia, and/or bacterial meningitis; bacteremia and bacterial meningitis were considered invasive bacterial infections (IBIs). SBIs rates were compared between SARS-CoV-2-positive and negative infants and stratified by age. We included 779 infants: 221 (28.4%) SARS-CoV-2-positive and 558 (71.6%) SARS-CoV-2-negative. The SBI rate in the SARS-CoV-2-positive group was 5.9% vs 22.9% in the SARS-CoV-2-negative group (p < 0.001; relative risk (RR) 0.26; [95% CI 0.15-0.44]); the most common infections were UTI (5.4% vs 22.0%; p < 0.001). The IBI rate was 0.5% in the SARS-CoV-2-positive group vs. 3.2% in the negative group (p = 0.024; RR 0.14 [95% CI 0.02-1.04]). There were no cases of bacterial meningitis in the positive infants. SARS-CoV-2-positive infants > 28 days of age had a decreased likelihood of SBI (RR 0.22 [95% CI 0.11-0.43]), with no cases of IBI identified.     Conclusions: Febrile infants < 90 days of age with SARS-CoV-2 infection are at significantly lower risk of SBIs than those who are SARS-CoV-2-negative. Nevertheless, the rate of UTI remains considerable in SARS-CoV-2-positive infants. SARS-CoV-2 detection may be relevant in considering IBI risk for well-appearing febrile infants 29-89 days of age. What is Known: • Febrile infants with laboratory-confirmed viral infections have a significantly lower risk of serious bacterial infections when compared to those without them. Data focusing on very young febrile infants with a SARS-CoV-2 infection is still limited. What is New: • Young febrile infants with SARS-CoV-2 infection are at significantly lower risk of serious bacterial infections than those who are SARS-CoV-2-negative. Nevertheless, the rate of urinary tract infection remains considerable. SARS-CoV-2 detection may be relevant in considering invasive bacterial infection risk for well-appearing febrile infants 29-89 days of age., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aim of the article is to improve the differential diagnosis of specific and nonspecific inflammatory bowel diseases. In Russia, this scientific direction is associated with the name of G.F. Lang, who performed in 1901-1902 the study "On ulcerative inflammation of the large intestine caused by balantidiasis". The etiology of specific colitis is associated with infection with parasites, bacteria and viruses that cause inflammation of the intestinal wall, diarrhea, often with an admixture of mucus, pus and blood. Specific colitis (SC) may be accompanied by fever, abdominal pain, and tenesmus. Bacterial colitis is commonly caused by Salmonella, Shigella, Escherichia coli , Clostridium difficile , Campylobacter jejuni , Yersinia enterocolitica , and Mycobacterium tuberculosis . Viral colitis is caused by rotavirus, adenovirus, cytomegalovirus, and norovirus. Parasitic colitis can be caused by Entamoeba histolytica and balantidia. In gay people, SC can cause sexually transmitted infections: Neisseria gonorrhoeae, Chlamydia trachomatis , and treponema pallidum, affecting the rectum. Stool microscopy, culture, and endoscopy are used to establish the diagnosis. Stool culture helps in the diagnosis of bacterial colitis in 50% of patients, and endoscopic studies reveal only nonspecific pathological changes. Differential diagnosis of SC should be carried out with immune-inflammatory bowel diseases (ulcerative colitis, Crohn's disease, undifferentiated colitis), radiation colitis and other iatrogenic bowel lesions. The principles of diagnosis and therapy of inflammatory bowel diseases associated with various etiological.

Infection can induce hemophagocytic lymphohistiocytosis (HLH) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We herein report a 52-year-old man who had HLH and AAV simultaneously, possibly caused by Enterococcus faecalis infective endocarditis. The HLH diagnosis was based on the HLH-2004 criteria. AAV was diagnosed based on a positive result for proteinase-3 ANCA and necrotizing vasculitis of the small vessels on a skin biopsy. He eventually died and was sent for autopsy after combination treatment of valve replacement, antibiotics, and immunosuppressants, including corticosteroids. This case involved a challenging diagnosis and treatment of HLH with various complications in an adult.

Background: The incidence of sepsis increases significantly with age, including a high incidence of bacterial infection in the old adults. Eosinopenia and the CIBLE score have been proposed in critically ill adults and in internal medicine wards. This study aimed to assess whether a low eosinophil count was associated with acute bacterial infection among hospitalized older adults, and to find the most efficient eosinophil count cut-off to differentiate acute bacterial infection from other inflammatory states., Methods: This was a prospective study from July 2020 to July 2022 in geriatric wards of the University Paul Brousse Hospital (Villejuif, France) including patients aged of 75 y/o or over suffering from fever or biological inflammation. Acute bacterial infection was assessed using biological identification and/or clinical and radiological data., Results: A total of 156 patients were included. Eighty-two (53%) patients suffered from acute bacterial infection (mean age (SD) 88.7 (5.9)). Low eosinophil count was independently associated with acute bacterial infection: OR [CI95%] 3.03 [1.04-9.37] and 6.08 [2.42-16.5] for eosinophil count 0-0.07 G/L and 0.07-0.172 G/L respectively (vs. eosinophil count > 0.172 G/L). Specificity and sensitivity for eosinophil count < 0.01 G/L and CIBLE score were 84%-49% and 72%-62%, respectively with equivalent AUCs (0.66 and 0.67)., Conclusion: Eosinophil count < 0.01 G/L is a simple, routinely used and inexpensive tool which can easily participate in antibiotic decisions for older adults. Further studies are needed to assess clinical benefits., Trial Registration: The study was registered at Clinical trial.gov (NCT04363138-23/04/2020)., (© 2023. The Author(s).)

Introduction: Bacteroides fragilis (B. fragilis) is considered to act in an anti-inflammatory manner on the intestinal tract. On the contrary, enterotoxigenic B. fragilis (ETBF), a subtype of B. fragilis, produces an enterotoxin (BFT; B. fragilis toxin), leading to asymptomatic chronic infections and colonic tumor formation. However, the impact of B. fragilis and ETBF on the clinical outcome of colorectal cancer (CRC) remains unclear. We aim to assess whether their presence affects the outcome in patients with CRC after curative resection., Methods: We obtained 197 pairs of matched formalin-fixed paraffin-embedded samples from cancerous and adjacent non-cancerous tissues of patients with pathological stage (pstage) II and III CRC after curative resection. The presence of B. fragilis and ETBF were estimated using real-time polymerase chain reaction, and recurrence-free survival (RFS) and overall survival (OS) of the patients were analyzed., Results: 16S rRNA for B. fragilis and bft DNA were detected in 120 (60.9%) and 12 (6.1%) of the 197 patients, respectively. B. fragilis-positive patients had better RFS than B. fragilis-negative patients, although that was not statistically significant. In subgroup analysis, better outcomes on RFS were observed in the presence of B. fragilis in pstage II and left-sided CRC. The association of B. fragilis positivity on OS was accentuated in the depth of T4 subgroup. No significant differences were observed in RFS and OS between ETBF and non-toxigenic B. fragilis., Conclusions: Our findings suggest that the presence of B. fragilis is associated with better outcomes in patients with pstage II and III CRC after curative resection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the characteristics and outcomes of infants aged 29-90 days who are febrile discharged from the pediatric emergency department (ED)., Study Design: This was a multicenter, retrospective cohort study of infants aged 29-90 days who visited any of the 7 Clalit Health Services pediatric EDs in Israel between January 1, 2019, and March 31, 2022. Infants who were febrile discharged from the ED after having blood and urine cultures taken were included. The primary outcome measure was the incidence of return visit (RV) to an ED. Secondary outcome measures were the incidence of invasive bacterial infection, urinary tract infection, pediatric intensive care unit admissions, and deaths. We assessed variables associated with the primary outcomes., Results: A total of 1647 infants were included. Their median (IQR) age at ED visit was 58.5 (47.7, 72.7) days, 53.1% were male. A total of 329 patients (20%) returned to the ED within 120 hours. Overall, 7.8% of discharged infants had a positive urine culture, 4 (0.2%) had a positive blood culture, and none had meningitis. One patient was admitted to the pediatric intensive care unit, and there was no death. Abnormal C-reactive protein was associated with RV among 61- to 90-day-old infants., Conclusions: Infants aged 29-90 days who were febrile and discharged following a protocol-driven pathway from the pediatric ED had a relatively high RV rate. However, the rate of urinary tract infection was relatively low, and rate of invasive bacterial infection was extremely low. There were no deaths or serious sequelae., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Bacterial infections and the concurrent inflammation have been associated with increased long-term cardiovascular (CV) risk. In patients receiving peritoneal dialysis (PD), bacterial peritonitis is a common occurrence, and each episode further increases late CV mortality risk. However, the underlying mechanism(s) remains to be elucidated before safe and efficient anti-inflammatory interventions can be developed. Damage-Associated Molecular Patterns (DAMPs) have been shown to contribute to the acute inflammatory response to infections, but a potential role for DAMPs in mediating long-term vascular inflammation and CV risk following infection resolution in PD, has not been investigated. We found that bacterial peritonitis in mice that resolved within 24h led to CV disease-promoting systemic and vascular immune-mediated inflammatory responses that were maintained up to 28 days. These included higher blood proportions of inflammatory leukocytes displaying increased adhesion molecule expression, higher plasma cytokines levels, and increased aortic inflammatory and atherosclerosis-associated gene expression. These effects were also observed in infected nephropathic mice and amplified in mice routinely exposed to PD fluids. A peritonitis episode resulted in elevated plasma levels of the DAMP Calprotectin, both in PD patients and mice, here the increase was maintained up to 28 days. In vitro , the ability of culture supernatants from infected cells to promote key inflammatory and atherosclerosis-associated cellular responses, such as monocyte chemotaxis, and foam cell formation, was Calprotectin-dependent. In vivo , Calprotectin blockade robustly inhibited the short and long-term peripheral and vascular consequences of peritonitis, thereby demonstrating that targeting of the DAMP Calprotectin is a promising therapeutic strategy to reduce the long-lasting vascular inflammatory aftermath of an infection, notably PD-associated peritonitis, ultimately lowering CV risk., Competing Interests: Author GG-M was employed by Premium Research, S.L. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cetin, Mazzarino, González-Mateo, Kopytina, Meran, Fraser, López-Cabrera, Labéta and Raby.)

Neurodegenerative diseases remain the most prevalent and unsolved health problems in human society, especially Alzheimer's disease (AD) and Parkinson's disease (PD). The pathogenesis, pathology, and potential clinical treatments of neurodegenerative diseases still require in-depth research. In the wake of the association between pandemics and a growing number of neurodegeneration patients, there has been growing speculation that infections are linked to AD and PD. The Aβ peptide is an important causal-related biomarker of AD and is reported to share structural and functional similarities with certain antimicrobial peptides, suggesting that it has a role in eliciting an immune response against microbes. But how neurodegeneration is related to bacterial chronic infection has not been thoroughly investigated. Using the data from genome-wide association studies (GWAS), we performed Mendelian Randomization (MR) and map 7 genes in multiple bacterial infection pathways as exposure, which show a significant association with the outcome of AD or PD. As co-verification, we perform Gene Set Enrichment Analysis (GSEA) on selected genetic variants incorporating their perturb-seq gene list (combining single-cell RNA-seq and CRISPR-based perturbations). We observed clustering of the differentially expressed genes (DEGs) in the upstream and downstream of AD and PD-related KEGG pathways, hence confirming their causal association with AD and PD and providing new perspectives on the true cause of neurodegeneration.

Background: Improved tools are required to detect bacterial infection in children with fever without source (FWS), especially when younger than 3 years old. The aim of the present study was to investigate the diagnostic accuracy of a host signature combining for the first time two viral-induced biomarkers, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and interferon γ-induced protein-10 (IP-10), with a bacterial-induced one, C-reactive protein (CRP), to reliably predict bacterial infection in children with fever without source (FWS) and to compare its performance to routine individual biomarkers (CRP, procalcitonin (PCT), white blood cell and absolute neutrophil counts, TRAIL, and IP-10) and to the Labscore., Methods: This was a prospective diagnostic accuracy study conducted in a single tertiary center in children aged less than 3 years old presenting with FWS. Reference standard etiology (bacterial or viral) was assigned by a panel of three independent experts. Diagnostic accuracy (AUC, sensitivity, specificity) of host individual biomarkers and combinatorial scores was evaluated in comparison to reference standard outcomes (expert panel adjudication and microbiological diagnosis)., Results: 241 patients were included. 68 of them (28%) were diagnosed with a bacterial infection and 5 (2%) with invasive bacterial infection (IBI). Labscore, ImmunoXpert, and CRP attained the highest AUC values for the detection of bacterial infection, respectively 0.854 (0.804-0.905), 0.827 (0.764-0.890), and 0.807 (0.744-0.869). Labscore and ImmunoXpert outperformed the other single biomarkers with higher sensitivity and/or specificity and showed comparable performance to one another although slightly reduced sensitivity in children < 90 days of age., Conclusion: Labscore and ImmunoXpert demonstrate high diagnostic accuracy for safely discriminating bacterial infection in children with FWS aged under and over 90 days, supporting their adoption in the assessment of febrile patients., Competing Interests: The financial support received by AG from MeMed as well as the commercial affiliation of authors NM, LE, LS, ES, EB, RN, TG, KO, EE with MeMed does not alter our adherence to all PLOS ONE policies on sharing data and materials. Other authors had no relationship relating to employment, consultancy, patents, products in development, marketed products, etc. with any of the funding organizations., (Copyright: © 2023 Lacroix et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Spontaneous bacterial peritonitis (SBP) is a common complication in patients with cirrhosis. The diagnosis of SBP is still mostly based on ascites cultures and absolute ascites polymorphonuclear (PMN) cell count, which restricts the widely application in clinical settings. This study aimed to identify reliable and easy-to-use biomarkers for both diagnosis and prognosis of cirrhotic patients with SBP., Methods: We conducted a retrospective study including 413 cirrhotic patients from March 2013 to July 2022 in the First Affiliated Hospital of Guangxi Medical University. Patients' clinical characteristics and laboratory indices were collected and analyzed. Two machine learning methods (Xgboost and LASSO algorithms) and a logistic regression analysis were adopted to screen and validate the indices associated with the risk of SBP. A predictive model was constructed and validated using the estimated area under curve (AUC). The indices related to the survival of cirrhotic patients were also analyzed., Results: A total of 413 cirrhotic patients were enrolled in the study, of whom 329 were decompensated and 84 were compensated. 52 patients complicated and patients with SBP had a poorer Child-Pugh score (P < 0.05). Patients with SBP had a greater proportion of malignancies than those without SBP(P < 0.05). The majority of laboratory test indicators differed significantly between patients with and without SBP (P < 0.05). Albumin, neutrophil-to-lymphocyte ratio (NLR), and ferritin-to-neutrophil ratio (FNR) were found to be independently associated with SBP in decompensated cirrhotic patients using LASSO algorithms, and logistic regression analysis. The model established by the three indices showed a high predictive value with an AUC of 0.808. Furthermore, increased neutrophils, ALP, and C-reactive protein-to-albumin ratio (CAR) were associated with the shorter survival time of patients with decompensated cirrhosis, and the combination of these indices showed a greater predictive value for cirrhotic patients., Conclusions: The present study identified FNR as a novel index in the diagnosis of SBP in decompensated patients with cirrhosis. A model based on neutrophils, ALP and CAR showed high performance in predicting the prognosis of patients with decompensated cirrhosis., (© 2023. The Author(s).)

Acute focal bacterial nephritis (AFBN) is a kidney disease characterized by a localized bacterial infection that manifests as an inflammatory mass. Most children with AFBN have nonspecific symptoms including fever, vomiting, and abdominal discomfort, and some develop neurological symptoms such as meningeal irritation, unconsciousness, and seizures as their condition worsens. This was 2 cases of AFBN with central nervous system manifestations in children, and we analyzed its possible mechanisms of the clinical and radiographic features. We experience 2 very unusual cases of AFBN which were linked to central nervous system abnormalities. A 6-year-old boy with AFBN and clinically moderate ncephalitis/encephalopathy with a reversible splenial lesion (MERS) presented with neurological symptoms, including unconsciousness and convulsions. The second case involved an 8-year-old child with AFBN-associated acute encephalopathy who exhibited neurological symptoms, including unconsciousness. According to previous research, AFBN is linked to central nervous system impairment. As a result, when a clinician meets a patient with an inexplicable fever caused by a neurological condition, he should pay attention to this diagnosis of AFBN and follow it in the abdominal graph., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: The impact of confirmed viral infections (CVI) on procalcitonin (PCT) levels in febrile infants aged 8-60 days with a bacterial illness (BI) is unknown. The objectives of the study were to (1) examine the association of CVI with PCT levels in patients with/without a concurrent BI, defined as bacteremia, meningitis, or urinary tract infection, and (2) assess PCT as a predictor of BI in infants with a concurrent CVI., Methods: In this single-center, retrospective cohort study, we examined febrile infants aged 8-60 days presenting between January 1, 2018 and December 31, 2020. PCT levels were compared between groups, according to results of bacterial cultures and viral tests, using the Wilcoxon rank test. The prediction ability of PCT to detect BI with/without concurrent CVI was assessed by using area under the curve from logistic regression., Results: Patients included: 404 BI-/CVI+, 73 BI+/CVI-, 48 BI+/CVI+, and 138 BI-/CVI-. Median PCT level in the BI+/CVI+ group was significantly lower when compared to BI+/CVI- (0.36 ng/mL vs 0.89 ng/mL), but significantly higher than the BI-/CVI- group (0.36 ng/mL vs 0.1 ng/mL). The presence of a CVI reduced the sensitivity of PCT in BI detection (68% vs 44%), with minimal impact specificity (93% vs 96%)., Conclusions: In previously healthy febrile infants 8-60 days old, the presence of a CVI reduces the sensitivity of PCT BI detection without impacting its specificity. The impact of a CVI on PCT levels in febrile infants has implications for how this marker of infection should be considered when assessing risk of BI in infants., (Copyright © 2023 by the American Academy of Pediatrics.)

Introduction: SMBA is a cutaneous form of CAEBV that predominantly affects adolescents and children from East Asian countries. It is characterized by local skin erythema, bullae, ulcers, necrosis, and scarring following a mosquito bite. Affected patients may experience IM-like systemic inflammatory reactions. SMBA mainly involves NK cells and has the potential to progress to NK/T-cell lymphoma or invasive NK-cell leukemia., Case Report: A 7-year-old female was admitted to the hospital owing to recurring fever, skin allergies, and multifocal severe ulcerative necrotic skin lesions affecting both lower limbs. The authors primarily suspected bacterial infection, and debridement was insufficient to manage it. Pathological examination of residual skin tissues around the necrotic lesion revealed EBER-positive T cells. Eventually, the patient was diagnosed with SMBA complicated by bacterial infection based on diagnostic criteria and pathology findings. The patient responded well to timely antiviral and antibacterial treatment, with no deterioration during regular follow-up visits., Conclusions: SMBA is a subtype of CAEBV that is characterized by severe skin ulceration and is easily missed or misdiagnosed. Based on its mosquito bite history, pathological characteristics, and laboratory indicators, SMBA could expand new diagnostic and therapeutic approaches to the ulcerative skin diseases.