Causal associations between gut microbiota and sepsis: A two-sample Mendelian randomization study.

BACKGROUND: Targeting the gut microbiota may become a new therapeutic to prevent and treat sepsis. Nonetheless, the causal relationship between specific intestinal flora and sepsis is still unclear. METHODS: A two-sample Mendelian randomization study was performed using the summary statistics of gut microbiota from the largest available genome-wide association study (n = 18,340). The summary statistics of sepsis were obtained from the UK Biobank (n = 486,484). Inverse-variance weighted, weighted median and MR-Egger were used to examine the causal association between gut microbiota and sepsis. Cochrane's Q test, MR-Egger intercept test, MR-PRESSO Global test and Rucker's Q'-test were used for sensitivity analyses. The leave-one method was used for testing the stability of MR results, and Bonferroni-corrected was used to test the strength of the causal relationship between exposure and outcome. RESULTS: Nine intestinal microflora were found causally associated with sepsis, and 11 intestinal microflora were causally associated with 28-day death in sepsis. Among them, Order Victivallales had a strong causality with lower risk of sepsis (OR = 0.86, 95% CI: 0.78-0.94, p = .00165) and lower 28-day mortality of sepsis (OR = 0.68, 95% CI: 0.53-0.87, p = .00179) after Bonferroni-corrected test. No pleiotropy was detected. CONCLUSIONS: Through the two-sample MR analysis, we identified the specific intestinal flora that had a causal relationship with the risk and prognosis of sepsis at the level of gene prediction, which may provide helpful biomarkers for early disease diagnosis and potential therapeutic targets for sepsis.

Rare case of intracranial hemorrhage associated with seoul virus infection diagnosed by metagenomic next-generation sequencing.

BACKGROUND: Seoul virus (SEOV) is a Hantavirus and the causative pathogen of Hemorrhagic Fever with Renal Syndrome (HFRS). Diagnosing SEOV infection is difficult because the clinical presentations are often undistinguishable from other viral or bacterial infections. In addition, diagnostic tools including serological and molecular assays are not readily available in the clinical settings. CASE REPORT: A 57-year-old male presented with fever and a sudden loss of consciousness in November 2019. Computed tomography (CT) scan showed subdural hematoma, subfalcine herniation, and brain infarction. He developed thrombocytopenia and elevated transaminases, but no rashes or obvious kidney damage. He reported having a rat bite. HFRS was suspected. The Hantavirus IgG was positive, and the metagenomic next-generation sequencing (mNGS) detected SEOV sequences directly in the blood. CONCLUSION: This report highlights the importance of suspecting SEOV infection in febrile patients with thrombocytopenia and elevated liver enzymes despite the absence of hemorrhagic manifestations of skin and renal syndromes. Next-generation sequencing is a powerful tool for pathogen detection. Intracranial hemorrhage and brain infarction as extrarenal manifestations of HFRS are rare but possible as demonstrated in this case.

The functions of SID1 transmembrane family, member 2 (Sidt2).

The SID1 transmembrane family, member 2, namely, Sidt2, is a highly glycosylated multichannel lysosomal transmembrane protein, but its specific physiological function remains unknown. Lysosomal membrane proteins are very important for the executive functioning of lysosomes. As an important part of the lysosomal membrane, Sidt2 can maintain the normal morphology of lysosomes and help stabilize them from the acidic pH environment within. As a receptor/transporter, it binds and transports nucleic acids and mediates the uptake and degradation of RNA and DNA by the lysosome. During glucose metabolism, deletion of Sidt2 can cause an increase in fasting blood glucose and the impairment of grape tolerance, which is closely related to the secretion of insulin. During lipid metabolism, the loss of Sidt2 can cause hepatic steatosis and lipid metabolism disorders and can also play a role in signal regulation and transport. Here, we review the function of the lysosomal membrane protein Sidt2, and focus on its role in glucose and lipid metabolism, autophagy and nucleotide (DNA/RNA) transport.

Correlation of serum albumin level on postoperative day 2 with hospital length of stay in patients undergoing emergency surgery for perforated peptic ulcer.

BACKGROUND: Perforated peptic ulcer (PPU) is a common emergency surgical condition and a significant cause of morbidity and mortality worldwide. While advances in surgical techniques have improved outcomes for patients with PPU, many factors still affect postoperative hospital stay and overall prognosis. One potential factor is the serum albumin (SA) level, a widely utilized marker of nutritional status that has been associated with length of stay and complications in various surgical procedures. AIM: To clarify the correlation of SA level on postoperative day 2 with hospital length of stay (HLOS) in patients undergoing emergency surgery for perforated peptic ulcer (PPU). METHODS: We retrospectively collected and analyzed clinical baseline data, including blood routine and SA levels, of patients who underwent emergency PPU surgery and postoperative treatment at the Lingnan Hospital, the Third Affiliated Hospital of Sun Yat-sen University between December 2012 and September 2021. Patients were grouped according to HLOS with 7 d as the cut-off value, and relevant indicators were analyzed using SPSS 26.0. RESULTS: Of the 37 patients undergoing emergency surgery for PPU referred to our department, 33 had gastric and 4 had duodenal ulcer perforation. The median HLOS was 10 d. There were 8 patients in the ≤ 7-d group (median HLOS: 7 d) and 29 patients in the > 7-d group (median HLOS: 10 d). The ≤ 7-d group had markedly higher SA on postoperative day 2 than the > 7-d group (37.7 g/L vs 32.6g/L; P < 0.05). The SA level on postoperative day 2 was a protective factor for patients with HLOS > 7 d (Odds ratio = 0.629, P = 0.015). The cut-off of SA on postoperative day 2 was 30.6g/L, with an area under the curve of 0.86 and a negative predictive value of 100% for the prediction of HLOS ≤ 7 d. CONCLUSION: The SA level on postoperative day 2 was associated with the HLOS in patients undergoing emergency surgery for PPU. The pre- and post-operative albumin levels should be monitored, and infusion of human SA should be considered in a timely manner.

Co-Infection Pneumonia with Mycobacterium abscessus and Pneumocystis jiroveci in a Patient without HIV Infection Diagnosed by Metagenomic Next-Generation Sequencing.

INTRODUCTION: Co-infection pneumonia with Mycobacterium abscessus (M. abscessus) and Pneumocystis jirovecii (P. jirovecii) is rarely reported in previously healthy patients without HIV infection. The diagnosis of pneumonia of M. abscessus and P. jirovecii remains challenging due to its nonspecific clinical presentation and the inadequate performance of conventional diagnostic methods. CASE REPORT: We report the case of a 44-year-old previously healthy male transferred to our hospital in February 2020 with a 4-month history of productive cough and one month of intermittent fever. At local hospital, the metagenomic next-generation sequencing(mNGS) detected P. jirovecii sequences in blood; with the antifungal therapy (Caspofungin, trimethoprim-sulfamethoxazole [TMP-SMX] and methylprednisolone [MP]), the patient still had hypoxemia, cough and fever. Then he was transferred to our hospital, the mNGS of bronchoalveolar lavage fluid (BALF) detected the sequences of M. abscessus and P. jirovecii. CD4+ T-lymphocytopenia in the peripheral blood cells was presented and HIV serology was negative. Caspofungin, TMP-SMX, clindamycin and MP were used to treat P. jirovecii pneumonia (PJP). Moxifloxacin, imipenem cilastatin and linezolid were used to treat M. abscessus infection. Clinical progress was satisfactory following antifungal combined with anti-M. abscessus therapy. CONCLUSION: Co-infection pneumonia with M. abscessus and P. jirovecii as reported here is exceptionally rare. mNGS is a powerful tool for pathogen detection. M. abscessus infection could be a risk factor for P. jirovecii infection. This case report supports the value of mNGS in diagnosing of M. abscessus and P. jirovecii, and highlights the inadequacies of conventional diagnostic methods.

Clinical descriptive analysis of severe Pneumocystis jirovecii pneumonia in renal transplantation recipients.

Pneumocystis jirovecii (P. jirovecii) pneumonia (PJP) is an opportunistic fungal infection after renal transplantation, which is always severe, difficult to diagnose, combined with multiple complications and have poor prognosis. We retrospectively analyzed clinical data, including risk factors, diagnosis, treatment and complications of seven clinical cases suffered with severe PJP after renal transplantation in our department in 2019. All the seven recipients were routinely prescribed with PJP prophylaxis after renal transplantation, and six of them suffered acute graft rejection before the infection. P. jirovecii sequence was identified in blood or broncho-alveolar lavage fluid (BALF) by the metagenomic next-generation sequencing (mNGS) in all patients. All the patients were improved with the therapy trimethoprim-sulfamethoxazole (TMP-SMX) combined with caspofungin for the PJP treatment, but suffered with complications including renal insufficiency, leukopenia, thrombocytopenia, gastrointestinal bleeding, mediastinalemphysema, pulmonary hemorrhage, and hemophagocytic syndrome and other severe infections. Taken together, mNGS is a powerful tool that could be used to diagnose PJP in renal transplantation recipients. And PJP prophylaxis should be prescribed during and after treatment for acute rejection. TMP-SMX is the first-line and effective drug for PJP treatment, but the complications are always life-threatening and lead to poor prognosis. We should pay attention to these life-threatening complications.

Potential value of autoantibodies as biomarkers of chronic graft-versus-host disease after allogeneic stem cell transplantation.

We investigated the value of autoantibodies as biomarkers of chronic graft-versus-host disease (cGVHD) by analyzing the autoantibody profiles of 65 patients (34 cGVHD and 31 non-cGVHD) surviving longer than three months after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Autoantibodies to at least one antigen were detected in 45 patients (70.8%), with multiple autoantibodies detected in 30 patients (46.2%). Antinuclear antibodies (ANAs) were the most frequently detected autoantibodies, with a significantly higher prevalence in non-cGVHD patients and cGVHD patients than that in healthy controls (HCs). ANA-nucleolar (ANA-N) was the main immunofluorescence pattern of ANA-positivity in both the non-cGVHD and cGVHD groups. There was a higher prevalence of anti-Ro52-positivity in non-cGVHD and cGVHD patients than in HC. Liver cGVHD was significantly associated with anti-Ro52-positivity. However, cGVHD activity and severity were not associated with the presence of autoantibodies. Similarly, there were no significant differences in overall survival or relapse among the four groups of patients expressing autoantibodies. Our results suggest that autoantibodies have limited value in predicting cGVHD.

Association between arterial hyperoxia and mortality in critically ill patients: A systematic review and meta-analysis.

PURPOSE: The relationship between arterial hyperoxia exposure and clinical outcome is under increasing scrutiny. We therefore performed an update meta-analysis to evaluate the effect of arterial hyperoxia on hospital mortality in critically ill adults. METHODS: We searched relevant articles for trials that investigated the relationship between arterial hyperoxia and mortality in critically ill adults. The end-point was hospital mortality of critically ill patients. RESULTS: Three RCTs and 26 cohort studies involving 257,223 patients were identified. Hyperoxia exposure was associated with increased mortality in critically ill patients (crude OR 1.42, 95% CI 1.26-1.61; adjusted OR 1.20, 95% CI 1.09-1.32). There was no change in significance for outcome in meta-analysis of RCTs (OR 1.36; 95% CI 1.04-1.77) and sensitivity analysis of the included prospective studies (OR 1.32; 95% CI 1.04-1.67). This association was also established in patients admitted to critical care units following cardiac arrest (adjusted OR 1.32; 95% CI 1.12-1.56), ischemic stroke (crude OR 1.31; 95% CI 1.03-1.65) and intracerebral hemorrhage (crude OR 1.47; 95% CI 1.19-1.81). CONCLUSIONS: The results of current meta-analysis suggest that arterial hyperoxia may be associated with increased hospital mortality in critically ill patients.

Outcome of patients with hepatorenal syndrome type 1 after liver transplantation: Hangzhou experience.

BACKGROUND: Patients with hepatorenal syndrome (HRS) type 1 have an extremely poor prognosis. Liver transplantation (LT) is the only treatment that can cure terminal stage liver disease and reverse HRS. However, the data showing the impact of LT on patients with HRS type 1 are limited. METHODS: The outcome and prognostic factors of 32 patients with HRS type 1 receiving LT were investigated. The natural course of renal recovery and the efficacy of continuous post-LT veno-veno hemodialysis (CVVH) were also evaluated. RESULTS: Overall patient mortality was 34.4% (11/32), with eight patients died during the first month after LT. Scoring model was based on independent prognostic factors for the model end-stage liver diseases (MELD) (risk ratio=1.169) and serum sodium (risk ratio=0.769). High MELD score (>36) or low serum sodium (< or =126 mEq/L) or both were associated with reduced patient survival. HRS was resolved in 30 patients (median time, 24 days). Eight patients received post-LT CVVH. The need for CVVH was associated with higher pretransplant serum creatinine, longer duration of HRS, more pretransplant CVVH, more intraoperative blood products infusion, lower intraoperative urine output, and higher serum creatinine at 1 week posttransplant. However, serum creatinine at 1 month posttransplant and patient survival did not differ significantly between patients with and without CVVH. CONCLUSION: Patients developing HRS type 1 in the absence of high MELD score and low serum sodium would benefit from LT.