Bacteroides fragilis alleviates necrotizing enterocolitis through restoring bile acid metabolism balance using bile salt hydrolase and inhibiting FXR-NLRP3 signaling pathway.

Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in premature infants with no specific treatments available. We aimed to identify the molecular mechanisms underlying NEC and investigate the therapeutic effects of Bacteroides fragilis on NEC. Clinical samples of infant feces, bile acid-targeted metabolomics, pathological staining, bioinformatics analysis, NEC rat model, and co-immunoprecipitation were used to explore the pathogenesis of NEC. Taxonomic characterization of the bile salt hydrolase (bsh) gene, enzyme activity assays, 16S rRNA sequencing, and organoids were used to explore the therapeutic effects of B. fragilis on NEC-related intestinal damage. Clinical samples, NEC rat models, and in vitro experiments revealed that total bile acid increased in the blood but decreased in feces. Moreover, the levels of FXR and other bile acid metabolism-related genes were abnormal, resulting in disordered bile acid metabolism in NEC. Taurochenodeoxycholic acid accelerated NEC pathogenesis and taurodeoxycholate alleviated NEC. B. fragilis displayed bsh genes and enzyme activity and alleviated intestinal damage by restoring gut microbiota dysbiosis and bile acid metabolism abnormalities by inhibiting the FXR-NLRP3 signaling pathway. Our results provide valuable insights into the therapeutic role of B. fragilis in NEC. Administering B. fragilis may substantially alleviate intestinal damage in NEC.

Emerging infection: streptococcal toxic shock-like syndrome caused by group B Streptococcus (GBS), Streptococcus agalactiae.

Streptococcus agalactiae or Group B Streptococcus (GBS) infections are commonly associated with infections in neonates and pregnant women. However, there has been a rising incidence in nonpregnant adults. The risk of GBS infection in nonpregnant adults is increased for patients of advanced age and those with underlying medical conditions such as diabetes mellitus and cancer. We present a 77-year-old female with type-2 diabetes mellitus, hypertension, and bilateral foot ulcers that presented in probable septic shock with necrotic foot ulcers and necrotizing fasciitis and underwent bilateral lower limb amputations. The patient fulfilled the Streptococcal Toxic Shock Syndrome (STSS) criteria as defined by The Working Group on Severe Streptococcal Infections. These criteria were created for group A Streptococcus (Streptococcus pyogenes). Our patient fulfilled the Working Group's criteria, except that the blood culture was positive for group B Streptococcus (Streptococcus agalactiae). Numerous studies demonstrate the importance of early detection and antibiotic treatment for GBS infections in general and early surgical management for necrotizing soft tissue infections (NSTIs) such as necrotizing fasciitis.

Kikuchi Disease "A Lupus Mimicker": A Case Report.

Kikuchi disease, also called, Kikuchi-Fujimoto disease or histiocytic necrotizing lymphadenitis, is a rare self-limiting illness with an unknown etiology and pathogenesis. It is predominantly seen among young females. The cardinal clinical features include fever and cervical lymphadenopathy. Skin eruptions have also been reported. In Oman, two cases have been reported to date, in 2005 and 2020, with only one case exhibiting skin manifestations. There is a paucity of disease in our country and worldwide. In this case report, we discuss the diagnosis of Kikuchi disease in a previously healthy 17-year-old Omani female who presented with fever, cervical lymphadenopathy, and malar rash. The clinical picture in this case resembled that of systemic lupus erythematosus. Due to the rarity of Kikuchi disease, particularly in our region, it is crucial to consider it as a differential diagnosis when a patient exhibits the aforementioned symptoms to prevent misdiagnosis and inappropriate treatment, as it can easily be misdiagnosed as systemic lupus erythematosus.

Risks of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis After Liver Transplantation.

Biliary complications are common after liver transplantation (LT). Endoscopic retrograde cholangiopancreatography (ERCP) is the preferred method to treat biliary complications. Nevertheless, ERCP is not without complications and may have a greater complication rate in the LT population. Knowledge of the prevalence, severity, and possible risk factors for post-ERCP pancreatitis (PEP) in LT recipients is limited. Therefore, this study aims to determine the incidence and severity of PEP and identify potential risk factors in LT recipients. This retrospective cohort included patients ≥18 years who underwent ≥1 ERCP procedures after LT between January 2010 and October 2021. Two hundred thirty-two patients were included, who underwent 260 LTs and 1125 ERCPs. PEP occurred after 23 ERCP procedures (2%) with subsequent mortality in three (13%). Multivariate logistic regression identified wire cannulation of the pancreatic duct as a significant risk factor for PEP (OR, 3.21). The complication rate of PEP after LT in this study was shown to be low and is lower compared to patients without a history of LT. Nevertheless, the mortality rate of this group of patients was notably higher.

Immune-mediated necrotizing myopathy: A comprehensive review of the pathogenesis, clinical features, and treatments.

Immune-mediated necrotizing myopathy (IMNM) is a rare and newly recognized autoimmune disease within the spectrum of idiopathic inflammatory myopathies. It is characterized by myositis-specific autoantibodies, elevated serum creatine kinase levels, inflammatory infiltrate, and weakness. IMNM can be classified into three subtypes based on the presence or absence of specific autoantibodies: anti-signal recognition particle myositis, anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase myositis, and seronegative IMNM. In recent years, IMNM has gained increasing attention and emerged as a research hotspot. Recent studies have suggested that the pathogenesis of IMNM is linked to aberrant activation of immune system, including immune responses mediated by antibodies, complement, and immune cells, particularly macrophages, as well as abnormal release of inflammatory factors. Non-immune mechanisms such as autophagy and endoplasmic reticulum stress also participate in this process. Additionally, genetic variations associated with IMNM have been identified, providing new insights into the genetic mechanisms of the disease. Progress has also been made in IMNM treatment research, including the use of immunosuppressants and the development of biologics. Despite the challenges in understanding the etiology and treatment of IMNM, the latest research findings offer important guidance and insights for delving deeper into the disease's pathogenic mechanisms and identifying new therapeutic strategies.

Introduction of Solid Foods in Preterm Infants and Its Impact on Growth in the First Year of Life-A Prospective Observational Study.

The aim of this study was to investigate whether age at introduction of solid foods in preterm infants influences growth in the first year of life. This was a prospective observational study in very low birth weight infants stratified to an early (<17 weeks corrected age) or a late (≥17 weeks corrected age) feeding group according to the individual timing of weaning. In total, 115 infants were assigned to the early group, and 82 were assigned to the late group. Mean birth weight and gestational age were comparable between groups (early: 926 g, 26 + 6 weeks; late: 881 g, 26 + 5 weeks). Mean age at weaning was 13.2 weeks corrected age in the early group and 20.4 weeks corrected age in the late group. At 12 months corrected age, anthropometric parameters showed no significant differences between groups (early vs. late, mean length 75.0 vs. 74.1 cm, weight 9.2 vs. 8.9 kg, head circumference 45.5 vs. 45.0 cm). A machine learning model showed no effect of age at weaning on length and length z-scores at 12 months corrected age. Infants with comorbidities had significantly lower anthropometric z-scores compared to infants without comorbidities. Therefore, regardless of growth considerations, we recommend weaning preterm infants according to their neurological abilities.

Progranulin mitigates intestinal injury in a murine model of necrotizing enterocolitis by suppressing M1 macrophage polarization.

Neonatal necrotizing enterocolitis (NEC) is a critical digestive disorder frequently affecting premature infants. Characterized by intestinal inflammation caused by activated M1 macrophages, modulation of macrophage polarization is considered a promising therapeutic strategy for NEC. It has been demonstrated that the growth factor-like protein progranulin (PGRN), which plays roles in a number of physiological and pathological processes, can influence macrophage polarization and exhibit anti-inflammatory characteristics in a number of illnesses. However, its role in NEC is yet to be investigated. Our research showed that the levels of PGRN were markedly elevated in both human and animal models of NEC. PGRN deletion in mice worsens NEC by encouraging M1 polarization of macrophages and escalating intestinal damage and inflammation. Intravenous administration of recombinant PGRN to NEC mice showed significant survival benefits and protective effects, likely due to PGRN's ability to inhibit M1 polarization and reduce the release of pro-inflammatory factors. Our findings shed new light on PGRN's biological role in NEC and demonstrate its potential as a therapeutic target for the disease.

RNF31-mediated IKKα ubiquitination aggravates inflammation and intestinal injury through regulating NF-κB activation in human and mouse neonates.

AIMS: Neonatal necrotizing enterocolitis (NEC) is a leading cause of intestine inflammatory disease, and macrophage is significantly activated during NEC development. Posttranslational modifications (PTMs) of proteins, particularly ubiquitination, play critical roles in immune response. This study aimed to investigate the effects of ubiquitin-modified proteins on macrophage activation and NEC, and discover novel NEC-related inflammatory proteins. MATERIALS AND METHODS: Proteomic and ubiquitin proteomic analyses of intestinal macrophages in NEC/healthy mouse pups were carried out. In vitro macrophage inflammation model and in vivo NEC mouse model, as well as clinical human samples were used for further verification the inhibitor of nuclear factor-κB kinase α (IKKα) ubiquitination on NEC development through Western blot, immunofluorescence, quantitative real-time polymerase chain reaction (qRT-PCR) and flow cytometry. KEY FINDINGS: We report here that IKKα was a new ubiquitin-modified protein during NEC through ubiquitin proteomics, and RING finger protein 31 (RNF31) acted as an E3 ligase to be involved in IKKα degradation. Inhibition of IKKα ubiquitination and degradation with siRNF31 or proteasome inhibitor decreased nuclear factor-κB (NF-κB) activation, thereby decreasing the expression of pro-inflammatory factors and M1 macrophage polarization, resulting in reliving the severity of NEC. SIGNIFICANCE: Our study suggests the activation of RNF31-IKKα-NF-κB axis triggering NEC development and suppressing RNF31-mediated IKKα degradation may be therapeutic strategies to be developed for NEC treatment.

Enhancing Early Detection of Necrotizing Soft Tissue Infections: The Role of the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) Score.

Background There is great variation in the etiology, predisposing organisms, incidence, clinical characteristics, severity, and consequences of skin and/or subcutaneous tissue infections. Extensive necrosis of the subcutaneous tissues and fascia is a characteristic of necrotizing soft tissue infections, which are frequently deadly. To change the course of treatment, this study highlights the need to find a tool that can quickly and accurately identify patients with necrotizing fasciitis (NF) and assist in making an early treatment decision. Methodology A prospective evaluation of 30 individuals with soft tissue infections was conducted using the laboratory risk indicator for necrotizing fasciitis (LRINEC). The patients were classified as low, intermediate, and high risk for the start of NF based on their LRINEC score. To assess the importance of the LRINEC score in forecasting the start of NF and its clinical consequences, patients in each group underwent appropriate management and statistical analysis. Results This study included 28 males (93.3%) and two females (6.7%). The associated p-value, recorded as 0.039, signifies statistical significance in the observed area under the receiver operating characteristic (ROC) curve. The p-value in risk categorization was found to be 0.296, which suggests that LRINEC helps in risk categorization with 100% sensitivity when used as a screening tool. Conclusion The early detection of necrotizing soft tissue infections, such as NF, is vital. The LRINEC score, based on routine lab tests, accurately distinguishes these infections. With high sensitivity and significant p-values, it helps stratify patients, guiding timely interventions and saving lives.

Clinicopathological characteristics and renal outcomes of adult patients with pauci-immune necrotizing glomerulonephritis according to ANCA status.

BACKGROUND: Pauci-immune necrotizing glomerulonephritis (PING) is commonly associated with the presence of antineutrophilic cytoplasmic antibodies (ANCAs) but a significant number of patients do not have these antibodies. The significance of ANCA-negativity in the context of Berden's classification of PING is not known. METHODS: A retrospective analysis was conducted on all patients with histopathological diagnosis of idiopathic PING irrespective of ANCA status diagnosed between January 1998 to December 2018 and followed up at renal clinic for > 12 months. All biopsies were reclassified by Berden's classification. Clinicopathological characteristics and renal outcomes of ANCA-positive and ANCA-negative patients were compared. RESULTS: Out of 134 patients, 66 (49.5%) were ANCA-negative. The mean age was 34.76 ± 13.3 years. Compared with the ANCA-positive patients, ANCA-negative patients had significantly greater prevalence of nephrotic-range proteinuria (74.23% Vs 57.9%, P = 0.036) with less extra-renal manifestations (P < 0.05)). On histology, focal and crescentic classes dominated with less number of globally sclerosed glomeruli (2.7% Vs 5.07%, P = 0.02) and more mesangial proliferation (22.7% Vs 4.41%, P = 0.002) in the ANCA-negative group, whereas sclerotic was predominant in the ANCA-positive group (P = 0.05). More patients achieved complete and partial recovery in ANCA-negative patients (42.4% Vs 20.5%, P < 0.05) with better renal survival (27.27% Vs 16.17%, log-rank test: P = 0.03) and less patient mortality (13.63% vs 30.8%, log-rank test: P = 0.04) at 2 years. CONCLUSION: Our study confirms high prevalence of ANCA negativity among our cohort and this group presents with isolated renal involvement with better renal and patient survival. The ANCA-positive group showed significantly more patients in the sclerotic class, lower 2-year renal survival, and higher 2-year mortality as compared to the ANCA-negative group. However, the complete and partial responses to treatment were significantly better in the ANCA-negative group. Key Points • This study shows a high prevalence of ANCA negativity in cases of PING in Pakistani population, as almost half of patients in this study did not have these antibodies. • This negativity is more prevalent in the Asian populations but its significance in the context of Berden's classification of PING is unknown. • ANCA-negative group exhibited less severe phenotype and better outcomes compared with ANCA-positive group.

Use of Split-Thickness Skin Grafts and Autologous Skin Cell Suspension in a Case of Extensive Fournier Gangrene.

Fournier gangrene (FG) is a life-threatening necrotizing soft-tissue infection of the perineum and external genitalia, which primarily occurs in obese, diabetic males. The mainstay of treatment is source control via early aggressive surgical excision. Wide surgical excision can result in significant soft tissue defects that can be disfiguring and difficult to close. The most common method of closure is split-thickness skin grafting (STSG). Recently, autologous skin cell suspension (ASCS) technology has been used in addition to STSG to provide better wound healing and closure. This patient experienced excellent wound progression, following FG, through the application of ASCS with STSG, despite challenges related to the wounds, anatomical location, comorbidities, size, and the patient's medical history.

Invasive Community-Acquired Methicillin-Resistant Staphylococcus aureus With Aortic Aneurysm in a 10-Year-Old Patient: A Case Report.

The clinical presentation of disseminated community-acquired Methicillin-resistant Staphylococcus aureus (MRSA) in young pediatric patients without a known predisposing risk factor poses a diagnostic dilemma due to its non-specific clinical symptoms. This can lead to delayed initiation of appropriate antibiotics and surgical interventions to achieve a favorable outcome and prevent mortality. Appropriate imaging with good clinical judgment is required in the management of this infection. Outpatient surveillance for subacute and chronic complications is required for a good long-term prognosis. Few reported cases of disseminated infections with aortic aneurysm exist in the literature. We report a case of a child without predisposing risk factors managed for community-acquired MRSA sepsis, acute respiratory distress syndrome (ARDS), multiple abscesses, osteomyelitis, and necrotizing pneumonia with a post-discharge unruptured aortic aneurysm. This case emphasizes the importance of post-discharge monitoring even in patients with favorable outcomes.

Community-acquired necrotizing pneumonia caused by methicillin-resistant Staphylococcus aureus in a healthy pregnant woman after being infected with influenza A: A case report for early warning.

A previously healthy woman, 5 weeks pregnant, was admitted to the intensive care unit in critical condition for septic shock and acute respiratory distress syndrome due to methicillin-resistant Staphylococcus aureus (MRSA) after being infected with Influenza for 3 days. The patient in this case suffered from severe sequelae due to necrotizing pneumonia and later died on the 20th day after admission. We would like to remind clinicians to be aware of this rare but serious diagnosis. The key is to begin appropriate treatment immediately because MRSA necrotizing pneumonia is mediated by toxins and once the toxins are released they cannot be limited by antibiotic treatments. Necrotizing pneumonia related to MRSA should be considered in young patients with pneumonia, sepsis, and neutropenia following seasonal influenza infection with rapidly progressive symptoms.

Coaxial plastic stent placement within lumen-apposing metal stents for the management of pancreatic fluid collections: a systemic review and meta-analysis.

Background/Aims: Coaxial placement of double pigtail plastic stents (DPPS) through lumen-apposing metal stents (LAMSs) is commonly performed to reduce the risk of LAMS obstruction, bleeding, and stent migration when used for the drainage of pancreatic fluid collections (PFCs). A systematic review and meta-analysis were performed to compare the outcomes of LAMS alone and LAMS with coaxial DPPS placement in the management of PFCs. Methods: A systematic review was conducted to identify studies comparing LAMS and LAMS/DPPS for PFC drainage. Primary outcomes included the rate of clinical success, overall adverse events (AEs), bleeding, infection, occlusion, and stent migration. The pooled effect size was summarized using a random-effects model and compared between LAMS and LAMS/DPPS by calculating odds ratios (ORs). Results: Nine studies involving 709 patients were identified (338 on LAMS and 371 on LAMS/DPPS). LAMS/DPPS was associated with a reduced risk of stent obstruction (OR, 0.59; p=0.004) and infection (OR, 0.55; p=0.001). No significant differences were observed in clinical success (OR, 0.96; p=0.440), overall AEs (OR, 0.57; p=0.060), bleeding (OR, 0.61; p=0.120), or stent migration (OR, 1.03; p=0.480). Conclusions: Coaxial DPPS for LAMS drainage of PFCs is associated with a reduced risk of stent occlusion and infection; however, no difference was observed in the overall AE rates or bleeding.

Does the site, size, and number of necrotic collections affect the outcome of necrotizing pancreatitis? - a prospective analysis.

PURPOSE: In patients with acute necrotizing pancreatitis (ANP), the site, size, and the number of acute necrotic collections (ANC) may determine the outcome of patients. The current study aimed to correlate the nature of ANC with the adverse outcomes in ANP patients. METHODS: This was a single-center, prospective study (August 2019-August 2022) recruiting patients with ANP, correlating the site, size, and number of ANC with the length of hospital stay, intensive care unit (ICU) stays, development of organ failure and infection, need for intervention, and mortality. RESULTS: A total of 114 patients (mean age: 37.3 ± 13.4 years, 85.1% males) with ANP were included in the study. The number and maximum diameter of collections significantly correlated with the length of the hospital and ICU stay and the need for intervention. Taking a cut-off size of 8 cm, the sensitivity and specificity for predicting the need for intervention were 82.7% and 74.2%, respectively. ANCs located in the perinephric, paracolic, subhepatic, and epigastric regions had a significant correlation with two or more adverse outcomes. Additional points were added to the modified CT severity index (mCTSI) based on the present study's findings. The new score had significantly higher AUROC than mCTSI for predicting infection, need for intervention, ICU stay > 1 week, and mortality. CONCLUSION: The site, size, and number of EPNs have a significant correlation with adverse clinical outcomes in patients with ANP. The inclusion of these parameters, along with present scoring systems, will help further improve the prognostication of patients.

Alcohol and Periodontal Disease: A Narrative Review.

The scientific literature dealing with alcohol and alcoholic beverages revealed that these drinks possess an adverse impact on periodontal tissues. Additionally, other principal risk factors include tobacco, smoking, poor oral hygiene, etc. It has been observed that among chronic alcoholics, there are further issues, such as mental, social, and physical effects, that promote alcoholism. These people may have weak immunity for defense against pathogenic organisms and bacteria. Thus, chances of gingival bleeding, swollen gums, bad breath, and increased bone loss are there. Different alcoholic beverages in the market cause less salivation; these beverages contain sugars that promote acid production in the oral cavity by pathogens that demineralize the enamel and damage gum and teeth. This chronic alcohol consumption can progress into different types of oral disorders, including cancer, halitosis, and caries, and is also associated with tobacco and smoking. Chronic alcohol consumption can cause alteration of the oral microbiome and increase oral pathogens, which lead to periodontal disease and an environment of inflammation created in the body due to malnutrition, diminished immunity, altered liver condition, brain damage, and gut microbiota alteration. Heavily colored alcoholic beverages produce staining on teeth and, due to less saliva, may cause other toxic effects on the periodontium. Over-dependency on alcohol leads to necrotizing lesions such as necrotizing gingivitis, necrotizing periodontitis, and necrotizing stomatitis. These pathological impairments instigate severe damage to oral structures. Therefore, proper counseling by the attending dental surgeon and related health professionals is urgently required for the patient on the basis that the individual case needs to go away from the regular heavy consumption of alcohol.