Puerperal mastitis caused by limited community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) clones.

Objective: To outline the epidemiology of puerperal mastitis caused by methicillin-resistant Staphylococcus aureus (MRSA) and evaluate the effect of an infection control bundle on its incidence. Methods: A surge in MRSA puerperal mastitis was noted in a community hospital in September 2009. MRSA samples from mastitis cases and the environment underwent typing using multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec), gene encoding surface protein A (spa), accessory gene regulator (agr), and pulsed-field gel electrophoresis (PFGE). The phenotypic characteristics, including superantigen toxin profiles, gene encoding Panton-Valentine leucocidin (pvl), and minimal inhibitory concentration (MIC) against vancomycin, were ascertained. Subsequently, an infection control bundle emphasizing contact precautions was introduced, and mastitis incidence rates pre- and post-intervention were compared. Results: The majority of cases occurred within 6 weeks post-delivery in first-time mothers. Of the 42 S. aureus isolates (27 from mastitis and 15 from colonized staff and environmental sources), 25 (92.6%) clinical and 3 (20%) colonized MRSA were identified as ST59-SCCmecVT-spa t437-agr group I with a vancomycin MIC of 1 mg/L, pvl-positive, and predominantly with a consistent toxin profile (seb-selk-selr). PFGE revealed 13 patterns; pulsotype B exhibited clonal relatedness between two clinical and three colonized MRSA samples. Post-intervention, the incidence of both mastitis and MRSA mastitis notably decreased from 13.01 to 1.78 and from 3.70 to 0.99 episodes per 100 deliveries, respectively. Conclusion: Distinct community-associated MRSA (CA-MRSA) clones were detected among puerperal mastitis patients and colonized staff. The outbreak was effectively controlled following the implementation of a targeted infection control bundle.

Comparative Analysis of Two Commercial Automated Systems with Agar Dilution for Oxacillin Susceptibility and Their Association with Genotypes of Invasive Staphylococcus aureus Isolates (2011-2021).

Background: Determining oxacillin susceptibility using reference methods and automated systems is crucial for treating invasive infections caused by Staphylococcus aureus. This study compares the oxacillin susceptibility results from the two automated systems with agar dilution and correlates them with genotypes of invasive S. aureus. Methods: Non-duplicate S. aureus invasive isolates were collected over an 11-year period. The oxacillin susceptibility was determined with Phoenix 100 (Jan 2011 to Aug 2018) or Vitek 2 (Sep 2018 to Dec 2021), and susceptibility for oxacillin and cefoxitin was determined with agar dilution. Methicillin-resistant S. aureus (MRSA) was confirmed with mecA existence, and the genotype was determined using SCCmec. The association between genotype and antibiotic susceptibility using two automated systems and agar dilution was evaluated. Results: A total of 842 invasive S. aureus, including 443 mecA+ MRSA and 399 mecA- MSSA, were collected. The susceptibility rates of oxacillin determined by two automated systems and agar dilution were 68.8% (76.8% for Phoenix 100 and 57.6% for Vitek 2) and 54.0%, respectively. When compared with the oxacillin susceptibility using agar dilution, the categorical agreement for Phoenix 100 and Vitek 2 were 0.46% and 0.88%, respectively (p < 0.001). One hundred and forty-three isolates were misinterpreted as oxacillin-susceptible S. aureus (OSSA) using automated systems while comparing with agar dilution, among which molecularly community-associated MRSA (CA-MRSA) outnumbered healthcare-associated MRSA (HA-MRSA) (99 vs 34, p < 0.001). There were 70 mecA+ OSSA (OS-MRSA) using agar dilution, among which 42 harbored SCCmec types were predominantly categorized as CA-MRSA (38, p < 0.001). Conclusion: The categorical agreement of Vitek 2 in determining oxacillin susceptibility and predicting mecA existence is comparable with agar dilution, whereas Phoenix 100 is not. Most of those ORSA determined by agar dilution but misinterpreted as OSSA by automated systems and OS-MRSA are categorized as CA-MRSA.

Endemic melioidosis in central Taiwan-A longitudinal case cohort study.

Background: Melioidosis is a systemic and suppurative disease endemic in the Southeast Asia. In Taiwan, most cases are reported in the southern region and no relevant profiles have been reported in central region. In this study, we performed the epidemiologic and clinical analyses from the melioidosis cases in central Taiwan. Methods: The demographic, clinical, laboratory, radiologic, and outcome profiles were collected retrospectively and analyzed from patients whom Burkhoderia pseudomallei was isolated from clinical specimens during the 12-year study period (2011-2022). Results: Totally 11 melioidosis cases (10 males and 1 female) were diagnosed, among them only 2 (18.2%) cases lived in suburban areas. Seven (63.6%) cases were diagnosed during 2019-2020, and diabetes mellitus was the most relevant comorbidity (5, 45.4%). All cases presented with fever at arrival, but only 4 (36.4%) and 2 (18.2%) cases presented with dyspnea and shock, respectively. Pneumonitis and extrapulmonary involvement were found in 5 cases (45.4%) each. Appropriate empiric and targeted antibiotic treatments were found in 4 (36.4%) and 10 (91.0%) case, respectively. Two cases (18.2%) succumbed to infection despite appropriate treatment including targeted antibiotics. Conclusion: Melioidosis has become endemic in central Taiwan. Septic patients who present with suppurative or undetermined foci and have unsatisfied responses to standard treatment should arouse clinicians to take melioidosis into consideration.

Repurposing Astragalus Polysaccharide PG2 for Inhibiting ACE2 and SARS-CoV-2 Spike Syncytial Formation and Anti-Inflammatory Effects.

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to global public health. In an effort to develop novel anti-coronavirus therapeutics and achieve prophylactics, we used gene set enrichment analysis (GSEA) for drug screening and identified that Astragalus polysaccharide (PG2), a mixture of polysaccharides purified from Astragalus membranaceus, could effectively reverse COVID-19 signature genes. Further biological assays revealed that PG2 could prevent the fusion of BHK21-expressing wild-type (WT) viral spike (S) protein and Calu-3-expressing ACE2. Additionally, it specifically prevents the binding of recombinant viral S of WT, alpha, and beta strains to ACE2 receptor in our non-cell-based system. In addition, PG2 enhances let-7a, miR-146a, and miR-148b expression levels in the lung epithelial cells. These findings speculate that PG2 has the potential to reduce viral replication in lung and cytokine storm via these PG2-induced miRNAs. Furthermore, macrophage activation is one of the primary issues leading to the complicated condition of COVID-19 patients, and our results revealed that PG2 could regulate the activation of macrophages by promoting the polarization of THP-1-derived macrophages into an anti-inflammatory phenotype. In this study, PG2 stimulated M2 macrophage activation and increased the expression levels of anti-inflammatory cytokines IL-10 and IL-1RN. Additionally, PG2 was recently used to treat patients with severe COVID-19 symptoms by reducing the neutrophil-to-lymphocyte ratio (NLR). Therefore, our data suggest that PG2, a repurposed drug, possesses the potential to prevent WT SARS-CoV-2 S-mediated syncytia formation with the host cells; it also inhibits the binding of S proteins of WT, alpha, and beta strains to the recombinant ACE2 and halts severe COVID-19 development by regulating the polarization of macrophages to M2 cells.

A case series report on successful management of patients with COVID-19-associated lymphopenia and potential application of PG2.

Background: Lymphopenia and the resultant high neutrophil-to-lymphocyte ratio (NLR) are hallmark signs of severe COVID-19, and effective treatment remains unavailable. We retrospectively reviewed the outcomes of COVID-19 in a cohort of 26 patients admitted to Chung Shan Medical University Hospital (Taichung City, Taiwan). Twenty-five of the 26 patients recovered, including 9 patients with mild/moderate illness and 16 patients with severe/critical illness recovered. One patient died after refusing treatment. Case presentation: We report the cases of four patients with high NLRs and marked lymphopenia, despite receiving standard care. A novel injectable botanical drug, PG2, containing Astragalus polysaccharides, was administered to them as an immune modulator. The decrease in the NLR in these four patients was faster than that of other patients in the cohort (0.80 vs. 0.34 per day). Conclusion: All patients recovered from severe COVID-19 showed decreased NLR and normalized lymphocyte counts before discharge. Administration of PG2 may be of benefit to patients with moderate to severe COVID-19 and lymphopenia.

Genotyping of methicillin-resistant Staphylococcus aureus isolates causing invasive infections using spa typing and their correlation with antimicrobial susceptibility.

Correlation of antimicrobial susceptibility patterns with particular spa types could help physicians select appropriate antibiotics for the treatment of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections. The aim of this study was to investigate invasive MRSA isolates through delineating the molecular typing results and correlating them with antibiotic susceptibility testing results. A total of 670 non-duplicate mecA-positive MRSA isolates from patients with invasive infections were collected from a 5-year nationwide antimicrobial surveillance programme [Tigecycline In vitro Surveillance in Taiwan (TIST)] and 58 spa types were identified among 639 isolates (95.4%) by determining the allelic profile of the spa gene using PCR and nucleotide sequencing. Six major spa types, including spa t002 (n = 103; 15.4%) and t037 (n = 253, 37.8%), were classified as healthcare-associated MRSA (HA-MRSA; 53.1%), while t437 (n = 151; 22.5%), t441 (n = 13; 1.9%), t1081 (n = 19; 2.8%) and t3525 (n = 14; 2.1%) were classified as community-associated MRSA (CA-MRSA; 29.4%). Antimicrobial susceptibility was determined by agar dilution or broth microdilution for various antibiotics, and Etest was also used both for daptomycin and vancomycin. The declining trend in vancomycin minimum inhibitory concentration (MIC) was in parallel with an increasing frequency of CA-MRSA. Antibiotic susceptibility patterns were correlated with particular spa types and this correlation could help physicians select appropriate antibiotics for the treatment of invasive MRSA infections.

Molecular epidemiology and phenotypes of invasive methicillin-resistant vancomycin-intermediate Staphylococcus aureus in Taiwan.

BACKGROUND: Patients with invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA), especially those with an elevated minimal inhibitory concentration (MIC) of vancomycin (VA), are likely to have treatment failure and poor outcomes. The aim of this study was to delineate and correlate the genotypes and phenotypes of clinical VA-intermediate S. aureus (VISA) from invasive infections in Taiwan. METHODS: Between 2006 and 2010, a total of 670 non-duplicate MRSA isolates were collected from patients with invasive infections, mostly from blood, as part of a nationwide antimicrobial surveillance program named Tigecycline in vitro Surveillance in Taiwan. Among them, 10 (1.5%) VISA (VA MIC = 4 mg/L) isolates were identified. Molecular typing with staphylococcal cassette chromosome mec (SCCmec), multilocus sequence typing, staphylococcal protein A (spa), mec-associated hypervariable region (dru), accessory gene regulator (agr), and pulse-field gel electrophoresis, and phenotypic analysis including antibiotic susceptibility testing, gene encoding Panton-Valentine leukocidin (pvl), and superantigenic toxin profiles, were analyzed. RESULTS: All but one isolate was defined as molecular health-care-associated MRSA: 6 as SCCmecIII-ST239-spa t037-agrI-dru7 (1 isolate) and dru14 (5 isolates), 2 as SCCmecII-ST5-spa t586-agrII-dru4, and one as SCCmecII-ST89-spa t3520-agrIII-dru7. One isolate was defined as SCCmecIV-ST59-spa t437-agrI-dru8, which was categorized as molecular community-associated MRSA. Five pulsotypes were identified; only one had a positive D-test and 3 were insusceptible to daptomycin (MIC ≧1 mg/L). Five isolates possessed sea-selk-selq, among them 4 belonged to SCCmecIII-ST239-spa t037-agrI. CONCLUSION: In this study, VISA was rarely isolated from invasive MRSA infections, and most cases harbored limited genotypes and corresponding phenotypes.

The Relationship between Long Noncoding RNA H19 Polymorphism and the Epidermal Growth Factor Receptor Phenotypes on the Clinicopathological Characteristics of Lung Adenocarcinoma.

The aim of the current study is to investigate potential associations among Long Noncoding RNA (LncRNA) H19 single nucleotide polymorphism (SNP) and epidermal growth factor receptor (EGFR) phenotypes on the clinicopathological characteristics of lung adenocarcinoma (LADC). Five loci of LncRNA H19 SNPs (rs217727, rs2107425, rs2839698, rs3024270, and rs3741219) were genotyped by using TaqMan allelic discrimination in 223 LADC patients with wild-type EGFR phenotype and 323 LADC individuals with EGFR mutations. After the statistical analyses, patients with the EGFR mutation were related to a higher distribution frequency of rs217727 SNP CT heterozygote (p = 0.030), and the female population with EGFR mutation demonstrated a higher distribution frequency of rs217727 SNP CT heterozygote (p < 0.001) and rs2107425 CT heterozygote (p = 0.002). In addition, the presence of LncRNA H19 SNP rs217727 T allele (CT + TT) in patients with EGFR wild-type was associated to higher tumor T status (stage III or IV, p = 0.037) and poorer cell differentiation status (poor differentiation, p = 0.012) compared to those EGFR wild-type individuals with LncRNA H19 SNP rs217727 CC allele. Besides, a prominently higher tumor T status was found in subjects with LncRNA H19 SNP rs2107425 T allele (CT + TT) (stage III or IV, p = 0.007) compared to EGFR wild-type LADC individuals with LncRNA CC allele in EGFR wild-type patients. Our findings suggest that the presence of LncRNA H19 SNP rs217727 is related to the EGFR mutation in LADC patients, and the LncRNA H19 SNP rs217727 and rs2107425 are associated with progressed tumor status for LADC patients with EGFR wild-type.

Astragalus Polysaccharide Injection (PG2) Normalizes the Neutrophil-to-Lymphocyte Ratio in Patients with Advanced Lung Cancer Receiving Immunotherapy.

OBJECTIVES: The neutrophil-to-lymphocyte ratio (NLR) is a prognostic marker in patients with cancer receiving immunotherapy. Recent studies have shown that a high NLR was associated with a poor response and decreased survival. However, there is no intervention to reverse abnormally high NLR and improve clinical outcomes. Astragalus polysaccharide injection (PG2) is an immunomodulatory therapy for cancer-related fatigue. This study aimed to examine whether PG2 might normalize the NLR and affect the overall survival of patients with lung cancer treated with immunotherapy. MATERIALS AND METHODS: We retrospectively examined the medical records of patients with lung cancer treated with immune checkpoint inhibitors (ICIs) between October 1, 2015 and November 30, 2019. All patients received ICI combination chemotherapies, and some similarly received PG2 (Control vs PG2). The NLR was assessed before treatment and 6 weeks after ICI initiation, and the survival data was collected at least 4 years after treatment initiation for the first enrolled patient. RESULTS: Fifty-three patients were included. Six weeks after ICI initiation, 91.3% of the patients in the PG2 group exhibited a predefined "Decrease or no change" in the NLR, which was 28% higher than that in the Control group (63.3%) (P = .028). The NLR significantly decreased by 31.60% from baseline in the PG2 group (P = .012), whereas it increased by 5.80% in the Control group (P = .572). Six weeks after ICI treatment initiation, both groups had a median NLR of 3.73, and the overall survival was also similar (PG2 vs Control, 26.1 months vs 25.4 months, respectively); however, the PG2 group had a higher median baseline NLR than the Control group (PG2 vs Control, 4.51 vs 2.81, respectively). CONCLUSION: This study demonstrated that PG2 could normalize the NLR in patients with lung cancer receiving ICI combination treatments.

Treatment of chronic hepatitis C regiments containing with recombinant interferon in patients with sustained virological response predicts risk of hepatocellular carcinoma: A meta-analysis.

Given that evidence supporting chronic hepatitis C (CHC) infection developed chance for hepatocellular carcinoma (HCC) following antiviral agents therapy is controversial. We conducted a meta-analysis to examine the risk.We evaluated 20 retrospective and prospective cohort studies published up to 31 December 2017 which investigated the association between sustained virological response (SVR) and incidence of HCC patients treated with monotherapy interferon (IFN) or IFN plus ribavirin (RBV) therapy. The primary outcome of the study was the cumulative incidence of HCC. Odds ratio (OR) was used to evaluate the index of effect size for the association between SVR and treatment with IFN alone or IFN/RBV in CHC patients.SVR patients demonstrated a lower incidence of HCC compared to non-SVR patients. Non-SVR patients had greater odds of HCC incidence compared to SVR patients in the treatment of IFN plus RBV (pooled OR = 7.405, 95% CI = 4.689 to 11.694, P < .001). Non-SVR patients had greater odds of HCC incidence compared to SVR patients in the treatment of IFN monotherapy (pooled OR = 4.135, 95% CI = 3.009 to 5.682, P < .001). Lack of SVR to IFN therapy was significantly associated with greater risk of HCC incidence (pooled OR = 5.035, 95% CI = 3.915 to 6.474, P < .001).SVR could be as a predictor of HCC in CHC patients treated with IFN or IFN plus RBV, and have important implications during HCC screening, whereby patients who fail to achieve SVR need to be screened more rigorously.

Association of Carbonic Anhydrase 9 Polymorphism and the Epithelial Growth Factor Receptor Mutations in Lung Adenocarcinoma Patients.

Carbonic anhydrase 9 (CA9) plays a vital role in lung cancer progression. The current study explored the effect of CA9 gene polymorphisms and the epidermal growth factor receptor (EGFR) mutations on the clinicopathological characters of lung adenocarcinoma. In this study, three loci of CA9 single nucleotide polymorphism (SNP) (rs2071676 A>G, rs3829078 A>G, and rs1048638 C>A) were genotyped using the TaqMan allelic discrimination method in 193 EGFR wild type individuals and 281 EGFR mutation subjects. After adjusting for age, gender, and cigarette smoking status in logistic regression, all three CA9 SNPs illustrated a non-significant difference for the distribution between the EGFR wild type group and EGFR mutation group. Nevertheless, a significantly lower rate of CA9 SNP rs2071676 AG (adjusted odds ratio (AOR): 0.40, 95% confidence interval (CI): 0.16-0.95, p = 0.039) and AG+GG (AOR: 0.43, 95% CI: 0.18-0.98, p = 0.046) were found in the male population with L858R EGFR mutation compared to men with EGFR wild type. In addition, the CA9 SNP rs2071676 AG+GG genotype were significantly correlated to the lower tumor stage of lung adenocarcinoma in the whole study population (p = 0.044) and EGFR wild type individuals (p = 0.033). For the male population, the presence of CA9 SNP rs2071676 AG+GG genotype was also correlated to a lower tumor stage (p = 0.037) and fewer lymph node invasion (p = 0.003) in those with EGFR wild type. In conclusion, the existence of CA9 SNP rs2071676 is associated with the rate of EGFR L858R mutation in males. Furthermore, the CA9 SNP rs2071676 is correlated to lower tumor stage and lower risk for developing lymph node metastasis in lung adenocarcinoma, mainly in the EGFR wild type.

Maintenance interferon therapy in chronic hepatitis C patients who failed initial antiviral therapy: A meta-analysis.

OBJECTIVES: To evaluate the effect of pegylated interferon maintenance therapy in patients with chronic hepatitis C who failed initial antiviral therapy. METHODS: This is a meta-analysis of 6 randomized controlled trials that met the eligibility criteria. In all, 2438 chronic hepatitis C patients who failed to achieve sustained virologic response after initial treatment with pegylated interferon and ribavirin (antiviral therapy nonresponders or relapsers) were enrolled; 1237 patients received maintenance therapy (Maintenance group) and 1201 received no treatment (Observation group). RESULTS: The pooled analyses found that patients in the Maintenance group had a significantly higher rate of normal alanine aminotransferase than did patients in the Observation group (pooled odds ratio [OR] 4.436, 95% confidence interval [CI] 1.225-16.064, P = .023), but there was no significant difference between the 2 groups in the incidence of hepatocellular carcinoma (pooled OR 0.872, 95% CI 0.501-1.519, P = .630), or the mortality rate (pooled OR 1.564, 95% CI 0.807-3.032, P = .185). CONCLUSIONS: Interferon-based maintenance therapy in patients with chronic hepatitis C who failed initial antiviral therapy improved liver inflammation as indicated by blood chemistry (alanine aminotransferase).

Plasma Soluble Urokinase-Type Plasminogen Activator Receptor Level as a Predictor of the Severity of Community-Acquired Pneumonia.

The urokinase-type plasminogen activator receptor (uPAR) mediates various cellular activities and is involved in proteolysis, angiogenesis, and inflammation. The objective of this study was to investigate the association between soluble uPAR (suPAR) levels and community-acquired pneumonia (CAP) severity. A commercial enzyme-linked immunosorbent assay (ELISA) was performed to measure the plasma suPAR levels in 67 healthy controls and 75 patients with CAP. Our results revealed that plasma suPAR levels were significantly elevated in patients with CAP compared with the controls, and antibiotic treatment was effective in reducing suPAR levels. The plasma suPAR levels were correlated with the severity of CAP based on the pneumonia severity index (PSI) scores. Furthermore, lipopolysaccharide (LPS)-stimulation significantly increased uPAR expression in RAW 264.7 macrophages. In conclusion, plasma suPAR levels may play a role in the clinical assessment of CAP severity; these findings may provide information on new targets for treatment of CAP.

Integrated safety summary of phase II and III studies comparing oral nemonoxacin and levofloxacin in community-acquired pneumonia.

BACKGROUND: Nemonoxacin, a novel nonfluorinated quinolone, has broad-spectrum antibacterial activity, including activity against antibiotic-resistant strains, and was developed for treating community-acquired pneumonia (CAP). This report provides an integrated safety summary of oral nemonoxacin from two phase II and one phase III clinical studies. METHODS: Patients with mild CAP were randomized for treatment with nemonoxacin 500 mg (NEMO-500MG), nemonoxacin 750 mg (NEMO-750MG), or levofloxacin 500 mg (LEVO), orally, once daily, for 7-10 days. Hematological, gastrointestinal, and hepatic disorders; electrocardiography abnormalities; and reported quinolone-associated clinical concerns were included in this analysis. RESULTS: A total of 520, 155, and 320 subjects were assigned to receive NEMO-500MG, NEMO-750MG, and LEVO, respectively. The incidence of adverse events (AEs) was the highest (54.8%) in the NEMO-750MG group (NEMO-500MG, 36.9%; NEMO-750MG, 54.8%; LEVO, 39.7%) and that of drug-related AEs was comparable between the three groups (NEMO-500MG, 22.9%; NEMO-750MG, 31.0%; LEVO, 22.5%). The majority (>80%) of the patients showed mild drug-related AEs and the distribution based on severity was similar between the groups. The most commonly reported drug-related AEs included neutropenia (NEMO-500MG, 2.5%; NEMO-750MG, 8.4%; LEVO, 4.4%), nausea (NEMO-500MG, 2.5%; NEMO-750MG, 7.1%; LEVO, 2.5%), leukopenia (NEMO-500MG, 2.3%; NEMO-750MG, 4.5%; LEVO, 3.1%), and increased alanine aminotransferase level (NEMO-500MG, 4.4%; NEMO-750MG, 0%; LEVO, 2.5%). CONCLUSION: Nemonoxacin was well tolerated and no clinically significant safety concerns were identified, suggesting that it possesses a desirable safety and tolerability profile similar to that of levofloxacin, and may be a suitable alternative to fluoroquinolones for treating patients with CAP.

Bergapten induces G1 arrest and pro-apoptotic cascade in colorectal cancer cells associating with p53/p21/PTEN axis.

Bergapten is a natural compound and has potent anticancer activities. In this study, we explored the cytotoxicity of bergapten on colorectal cancer (CRC) cell DLD-1 and LoVo and its underlying mechanisms. We observed that bergapten (30 and 50 µM) decreased the viability of the CRC cells and induced the G0/G1 and sub-G1 phase arrest. Furthermore, immunoblotting results indicated that bergapten increased p53, phospho-p53(Ser-46), p21, PUMA, Bax, PTEN, and the caspase-9 and caspase-3 cleavage, but decreased cyclin E, CDK2, and phosphor-AKT(Ser-473) in the CRC cells. Inhibition of p53 by pifithrin-α reversed the bergapten-induced p53-mediated apoptotic cascade and restored the survival signaling and cell viability. Collectively, our findings reveal that bergapten decrease the cell viability and induce cell cycle arrest in the CRC cells, which may be attributed to p53-mediated apoptotic cascade, upregulation of p21 and PTEN, and inhibition of AKT.

Association of Drug Metabolic Enzyme Genetic Polymorphisms and Adverse Drug Reactions in Patients Receiving Rifapentine and Isoniazid Therapy for Latent Tuberculosis.

Weekly rifapentine and isoniazid therapy (3HP) is the most frequent treatment for latent tuberculosis infection (LTBI). However, the association between major adverse drug reactions (ADRs) and drug metabolic enzyme single-nucleotide polymorphisms (SNPs) remains unclear. In this study, 377 participants who received the 3HP regimen were recruited and examined for genotyping of CYP5A6, CYP2B6, CYP2C19, CYP2E1, and NAT2 SNPs. In our study, 184 participants (48.4%) developed ADRs. Moreover, CYP2C19 rs4986893 (TT vs. CC+CT, odds ratio [OR] [95% CI]: 2.231 [1.015-4.906]), CYP2E1 rs2070676 (CC vs. CG+GG, OR [95% CI]: 1.563 [1.022-2.389]), and CYP2E1 rs2515641 (CC vs. CT+TT, OR [95% CI]: 1.903 [1.250-2.898]) were associated with ADR development. In conclusion, CYP2C19 and CYP2E1 SNPs may provide useful information regarding ADRs in LTBI patients receiving the 3HP regimen.

Human papillomavirus prevalence and behavioral risk factors among HIV-infected and HIV-uninfected men who have sex with men in Taiwan.

Human papillomavirus (HPV) infection is associated with cancer and can be prevented through vaccination. Few studies from Taiwan have reported on HPV infection among human immunodeficiency virus (HIV)-infected subjects. The aim of this study was to examine the prevalence of HPV infection among men who have sex with men (MSM) with and without HIV infection in Taiwan, and explore the behavioral risk factors thereof.We conducted a cross-sectional study in Taiwan during 2013 to 2016 to collect data on MSM aged 20 years or older. We used a questionnaire in a face-to-face interview, and subsequently collected oral, anal, and genital specimens from HIV-infected and HIV-uninfected subjects. Multivariate analysis was performed to predict factors associated with high-risk HPV (HR-HPV) positivity.Overall, 279 subjects, including 166 (59.5%) HIV-uninfected and 113 (40.5%) HIV-infected men were enrolled. Compared to HPV-negative subjects, HPV-positive subjects had significantly higher rates of receptive anal sex (91.3% vs 75.6%), substance use (22.6% vs 11%), history of sexually transmitted infections (75.7% vs 38.4%), anogenital or oral warts (39.1% vs 6.72%), syphilis (32.2% vs 11.6%), and HIV infection (69.6% vs 20.1%). We detected 489 HPV deoxyribonucleic acid (DNA) types (through 379 viable specimens), of which 43.6%, 5.7%, 56.4%, and 10.4% were HR-HPV type, HPV type 16, low-risk HPV types, and HPV type 6, respectively. In multivariate analysis, HIV-infected subjects had a significantly higher prevalence of HR-HPV infection (adjusted odds ratio, 5.80; 95% confidence interval, 2.57-13.11), compared to HIV-uninfected subjects.These results suggest that the prevalence of HPV infection was high among HIV-infected MSM. Additionally, anal HPV infection was observed to be common among both HIV-infected and HIV-uninfected MSM in Taiwan. The prevalence of oral and genital HPV infection, HR-HPV DNA types, and multiple HPV types was higher in HIV-infected subjects than in HIV-uninfected subjects. As only 35% of subjects practiced safe sex, we recommend routine HPV vaccination with 4-valent HPV or 9-valent HPV vaccines for both MSM, and HIV-infected subjects.

Circulating level of high mobility group box­1 predicts the severity of community­acquired pneumonia: Regulation of inflammatory responses via the c­Jun N­terminal signaling pathway in macrophages.

High mobility group box­1 (HMGB­1) has been reported to serve significant roles in various inflammatory diseases. However, the correlation between the circulating level of HMGB­1 and severity of community­acquired pneumonia (CAP) remains unclear. The present study investigated differential alterations in plasma HMGB­1 levels of patients with CAP prior to and following antibiotic treatment, and further analyzed the association between CAP severity and HMGB­1 levels. Furthermore, lipopolysaccharide (LPS)­induced HMGB­1 expression in RAW264.7 macrophages and the relevant signaling pathways were examined. Plasma HMGB­1 levels of 90 patients with CAP and 52 healthy controls were measured using a commercial ELISA. The levels of plasma HMGB­1 were significantly elevated in CAP patients compared with the controls, and antibiotic treatment was effective in reducing HMGB­1 levels. Plasma HMGB­1 correlated with the pneumonia severity index score (r=0.566, P<0.001). Furthermore, LPS­stimulation significantly upregulated HMGB­1 secretion via the c­Jun N­terminal kinase (JNK) signaling pathway in RAW264.7 macrophages, whereas pretreatment with the JNK inhibitor SP600125 markedly downregulated LPS­induced HMGB­1 levels. In conclusion, plasma HMGB­1 levels may serve a role in the diagnosis and clinical assessment of CAP severity. These findings may provide information on novel targets for the treatment of CAP.