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Background: Screening and treating healthcare workers (HCWs) for latent tuberculosis infection (LTBI) are essential for tuberculosis (TB) infection control. Adverse drug reactions (ADRs) to anti-TB drugs present challenges to patient safety and treatment completion. Objective: This study investigated the association between human leukocyte antigen (HLA) alleles and the risk of ADRs, especially drug hypersensitivity (DHS) and hepatotoxicity, in HCWs with LTBI receiving isoniazid (INH) and rifampin (RIF) therapy. Methods: Korean HCWs with LTBI who received a 3 month INH and RIF regimen were included in this study. HLA genotyping was performed on HCWs who experienced ADRs during treatment, as well as the control group consisted of individuals who did not develop ADRs. Results: Of the 67 patients, 29 (43.2%) experienced ADRs during INH and RIF therapy. The HLA-A*11:01 allele was more frequent in patients with DHS without hepatotoxicity (DSH+/H−) compared to the control group (DHS−/H−) (4/9, 44.4% vs. 3/38, 7.9%; odd ratio [OR], 8.554; 95% confidence interval [CI], 1.415–59.869; p = 0.018). Conversely, HLA-DPB1*05:01 was associated with an increased risk of hepatotoxicity regardless of DHS (10/20, 50% vs. 5/38, 13.2%; OR, 5.323; 95% CI, 1.493–21.518; p = 0.011). In the DHS with hepatotoxicity group (DHS+/H+), HLA-DPB1*05:01 was present in a higher proportion (3/5, 60% vs. 5/38, 13.2%; OR, 8.912; 95% CI, 1.110–92.993; p = 0.037), whereas HLA-A*11:01 was not observed in this group. Conclusions: The HLA-A*11:01 allele was associated with an increased risk of DHS without hepatotoxicity, whereas the HLA-DPB1*05:01 allele was associated with an increased risk of hepatotoxicity. [ABSTRACT FROM AUTHOR]

(1) Objectives: This study investigated the optimal duration of antibiotic therapy and determined the risk factors associated with relapse in patients with culture-proven septic arthritis of native joints. (2) Methods: A retrospective review was conducted on patients aged ≥18 years diagnosed with native joint septic arthritis, with bacteria isolated from joints and/or blood. The exclusion criteria were prosthetic joint infections and cases with no identified microorganisms. The outcomes were assessed in the remission and relapse groups. (3) Results: Among 479 patients with native joint septic arthritis, 137 met the inclusion criteria, with a median follow-up duration of 2.7 years. The relapse rate was 9.5%, which mainly occurred within 30 days after antibiotic treatment completion. Compared with the remission group, the relapse group showed a significantly higher proportion of cases that received antibiotic therapy for ≤ 4 weeks (4.8% vs. 46.2%, p < 0.001), synovial fluid white blood cell (WBC) counts ≥150 × 103/mm3 (25.3% vs. 60.0%, p = 0.030), acute kidney injury (19.2% vs. 50%, p = 0.024), and extended-spectrum beta-lactamases-producing Enterobacteriaceae (0.8 vs. 15.4%, p = 0.024). Independent risk factors for relapse were determined as antibiotic therapy duration of ≤ 4 weeks (odds ratio (OR), 25.47; 95% confidence interval (CI), 1.57–412.33; p = 0.023) and synovial fluid WBC counts ≥150 × 103/mm3 (OR, 17.46; 95% CI, 1.74–175.62; p = 0.015). (4) Conclusions: Patients with native joint septic arthritis require vigilant monitoring for relapse, particularly when treated with antibiotic regimens administered for less than four weeks or when synovial aspirates exhibit elevated WBC counts at diagnosis. [ABSTRACT FROM AUTHOR]

This study aimed to compare clinical characteristics and outcomes in patients with native joint septic arthritis (NJSA) due to methicillin-resistant Staphylococcus aureus (MRSA) in comparison to methicillin-sensitive S. aureus (MSSA) and identify treatment failure risk factors. We conducted a multi-center retrospective study on adult NJSA patients at three teaching hospitals in South Korea from 2005 to 2017. Among 101 patients diagnosed with S. aureus NJSA, 39 (38.6%) had MRSA strains. Compared to MSSA, patients with MRSA had a higher prevalence of nosocomial infections (17.9% vs. 1.6%; p = 0.005) and received inappropriate antibiotics within 48 h more frequently (74.4% vs. 0%; p < 0.001). In total, twenty patients (19.8%) experienced treatment failure, which encompassed five patients (5.0%) who passed away, nine (8.9%) requiring repeated surgical drainage after 30 days of antibiotic therapy, and seven (6.9%) with relapse. The MRSA group showed a higher rate of overall treatment failure (33.3% vs. 11.3%; p = 0.007) with a notably increased frequency of requiring repeated surgical interventions after 30 days of antibiotic therapy (17.9% vs. 3.2%, p = 0.026), in contrast to the MSSA group. Independent risk factors for treatment failure included Charlson comorbidity score, elevated CRP levels, and methicillin resistance. Methicillin resistance is an independent risk factor for treatment failure, emphasizing the need for vigilant monitoring and targeted interventions in MRSA-related NJSA cases. [ABSTRACT FROM AUTHOR]

Patients with COVID-19 have been reported to experience gastrointestinal symptoms as well as respiratory symptoms, but the effects of COVID-19 on the gut microbiota are poorly understood. We explored gut microbiome profiles associated with the respiratory infection of SARS-CoV-2 during the recovery phase in patients with asymptomatic or mild COVID-19. A longitudinal analysis was performed using the same patients to determine whether the gut microbiota changed after recovery from COVID-19. We applied 16S rRNA amplicon sequencing to analyze two paired fecal samples from 12 patients with asymptomatic or mild COVID-19. Fecal samples were selected at two time points: during SARS-CoV-2 infection (infected state) and after negative conversion of the viral RNA (recovered state). We also compared the microbiome data with those from 36 healthy controls. Microbial evenness of the recovered state was significantly increased compared with the infected state. SARS-CoV-2 infection induced the depletion of Bacteroidetes, while an abundance was observed with a tendency to rapidly reverse in the recovered state. The Firmicutes/Bacteroidetes ratio in the infected state was markedly higher than that in the recovered state. Gut dysbiosis was observed after infection even in patients with asymptomatic or mild COVID-19, while the composition of the gut microbiota was recovered after negative conversion of SARS-CoV-2 RNA. Modifying intestinal microbes in response to COVID-19 might be a useful therapeutic alternative. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a common disorder involving depressive mood and decreased motivation. Due to its high heterogeneity, novel biomarkers are required to diagnose MDD. In this study, a proteomic method was used to identify a new MDD biomarker. Using sequential window acquisition of all theoretical mass spectra acquisitions and multiple reaction monitoring analysis via mass spectrometry, relative and absolute quantification of proteins in the sera was performed. The results of the relative quantitation by sequential window acquisition for all theoretical mass spectra data showed that seven proteins were significantly differently expressed between MDD patients and other patients with remission status. However, absolute quantification by multiple reaction monitoring analysis identified prothrombin as the only significantly upregulated protein in the depressive state compared to remission (p < 0.05) and was, thus, subsequently selected as an MDD biomarker. The area under the curve for prothrombin was 0.66. Additionally, increased prothrombin/thrombin induced hyper-activation of platelets via activating protease-activated receptors, a feature associated with MDD; specifically, activated platelets secrete various molecules related to MDD, including brain-derived neurotropic factors and serotonin. Therefore, prothrombin is a potential screening, prognostic, and diagnostic marker for MDD. [ABSTRACT FROM AUTHOR]

Objectives: To investigate antibody production in asymptomatic and mild COVID-19 patients. Methods: Sera from asymptomatic to severe COVID-19 patients were collected. Microneutralization (MN), fluorescence immunoassay (FIA), and enzyme-linked immunosorbent assay (ELISA) were performed. Results: A total of 70 laboratory-confirmed COVID-19 patients were evaluated, including 15 asymptomatic/anosmia, 49 mild symptomatic, and 6 pneumonia patients. The production of the neutralizing antibody was observed in 100% of pneumonia, 93.9% of mild symptomatic, and 80.0% of asymptomatic/anosmia groups. All the patients in the pneumonia group showed high MN titer (≥1:80), while 36.7% of mild symptomatic and 20.0% of asymptomatic/anosmia groups showed high titer (p < 0.001). Anti-SARS-CoV-2 antibodies could be more sensitively detected by FIA IgG (98.8%) and ELISA (97.6%) in overall. For the FIA IgG test, all patients in the pneumonia group exhibited a high COI value (≥15.0), while 89.8% of mild symptomatic and 73.3% of asymptomatic/anosmia groups showed a high value (p = 0.049). For the ELISA test, all patients in the pneumonia group showed a high optical density (OD) ratio (≥3.0), while 65.3% of mild symptomatic and 53.3% of asymptomatic/anosmia groups showed a high ratio (p = 0.006). Conclusions: Most asymptomatic and mild COVID-19 patients produced the neutralizing antibody, although the titers were lower than pneumonia patients. ELISA and FIA sensitively detected anti-SARS-CoV-2 antibodies. [ABSTRACT FROM AUTHOR]

Gut dysbiosis is regarded as a pathogenetic factor of nonalcoholic fatty liver disease (NAFLD), but its role in NAFLD persistence is unknown. We investigated the influence of the gut microbiota on persistent NAFLD. This cohort study included 766 subjects with 16S ribosomal RNA (rRNA) gene sequencing data from fecal samples at baseline who underwent repeated health check-up examinations. Fatty liver was determined using ultrasound at baseline and follow-up. Participants were categorized into four groups: none (control), developed, regressed, or persistent NAFLD. The persistent NAFLD group had lower richness compared with the control group. Significant differences were also found in both non-phylogenic and phylogenic beta diversity measures according to NAFLD persistence. Pairwise comparisons indicated that taxa abundance mainly differed between the control and persistent NAFLD groups. A relative high abundance of Fusobacteria and low abundance of genera Oscillospira and Ruminococcus of the family Ruminococcaceae and genus Coprococcus of the family Lachnospiraceae were found in the persistent NAFLD group. Based on the functional predictions, pathways related to primary and secondary bile acid biosynthesis were highly detected in the persistent NAFLD group compared with the control group. These findings support that the composition of the gut microbiome associated with dysregulation of bile acid biosynthetic pathways may contribute to the persistence of NAFLD. This is the first cohort study to demonstrate the influence of microbiota on persistent NAFLD. Our findings may help identify potential targets for therapeutic intervention in NAFLD. [ABSTRACT FROM AUTHOR]

The changes in the gut microbiota of healthy hepatitis B virus (HBV) carriers, including asymptomatic and non-cirrhotic subjects, have been rarely scrutinized. From 1463 faecal samples in health examinees, in total 112 subjects, including 36 hepatitis B surface antigen (HBsAg)-positive and 76 control subjects, were included. Twenty-eight of 36 HBsAg-positive individuals (78%) showed normal alanine aminotransferase (ALT) levels (normal ALT group), whereas eight subjects exhibited elevated ALT levels (22%, high ALT group). By using 16S rRNA gene sequencing, the distance between normal and high ALT groups among HBsAg-positive subjects showed a significant separation after the pairwise comparison of weighted UniFrac distance (permutational analysis of variance q-value = 0.039), when compared with the distances to the control group. In comparison with the control group, the normal ALT group had Anaerostipes as a significant taxon that showed a positive association (Coefficient (Coef.) = 0.028, q = 0.039). Desulfovibrio (Coef. = 0.54, q = 0.014) and Megasphaera (Coef. = 1.41, q = 0.030) showed positive correlations, and Acidaminococcus (Coef. = −1.31, q = 4.15 × 10−75) exhibited a negative correlation with high ALT level. Gut microbial composition was different according to HBV-induced serum ALT levels, indicative of a potential link between gut and liver metabolism. [ABSTRACT FROM AUTHOR]