Tzu Chi Foundation

In this double-blind randomised controlled trial of 58 patients with 58 diabetic foot ulcers, a topical probiotic formulation in soybean concentrate significantly accelerated wound healing compared with placebo. The mean time to complete healing was 89.6 vs. 165.9 days (P = 0.012), with higher healing rates from week 20 onwards. The treatment was safe and well tolerated, supporting topical probiotics as a promising adjunctive therapy for chronic diabetic foot ulcers.

A nucleotide substitution in codon 97 of HLA-B*40:337:01N results in a novel null allele, HLA-B*40:337:02N.

To evaluate the prognostic values of 18F-FDG PET-derived whole-body imaging features in patients with metastatic lung adenocarcinoma treated with EGFR-targeted therapies. We retrospectively analyzed 249 patients with lung adenocarcinoma who underwent pre-treatment 18F-FDG PET and were treated with EGFR-targeted agents. The patients were divided into analog (n = 150) and digital (n = 99) PET cohorts. Whole-body and primary tumor respiratory-stable imaging features were extracted. The prognostic values of the study variables for progression-free (PFS) and overall survival (OS) were assessed using univariate and multivariate Cox regression analyses across the analog and digital PET cohorts. Total sphericity and primary tumor inverse difference normalized were independent predictors of both PFS and OS. The total metabolic tumor volume was another independent predictor of OS. Combined models integrating these imaging biomarkers with clinical variables outperformed the traditional staging system (c-indices for PFS: 0.649 versus 0.550 for analog and 0.668 versus 0.583 for digital PET cohorts; for OS: 0.694 versus 0.562 for analog and 0.728 versus 0.579 for digital PET cohorts). Our models showed consistent predictive values across subgroups based on sex, EGFR mutation subtype, and clinical stage. Our results indicate that models integrating whole-body 18F-FDG PET features with traditional variables can enhance survival prediction and may support personalized treatment strategies for patients with lung adenocarcinoma treated with EGFR-targeted therapies.

Few genome-wide association studies have examined genetic variants associated with hepatocellular carcinoma (HCC) risk in individuals seronegative for HBsAg and anti-HCV, and the long-term impact of these variants remains uncertain. This multi-stage study analyzed adults >30 years old who were seronegative for HBsAg and anti-HCV. In the genome-wide association study discovery phase, 765 HCC cases and 9,949 controls were analyzed for 308,693 SNPs, with significant SNPs confirmed in community-based (171 HCC cases, 684 controls) and hospital-based (470 HCC cases, 5,460 controls) validation sets. A cohort of 67,909 participants, followed from 2012 to 2021, was used to evaluate the long-term HCC risk associated with these variants. Ten SNPs in PNPLA3/SAMM50 were significantly associated with HCC risk (p <1.62 × 10-7) and were in high linkage disequilibrium. Three SNPs (rs738409, rs2281135, rs2235776) were replicated and demonstrated strong associations with HCC, independent of steatosis. Over 267,238 person-years of follow-up, 32 new HCC cases occurred, with elevated risks observed in individuals homozygous for the risk genotypes: GG (rs738409), AA (rs2281135), and TT (rs2235776). The adjusted hazard ratios (95% CI) were 3.37 (1.32-8.63), 2.80 (1.06-7.37), and 2.64 (0.91-7.66), respectively. In allelic models, carriers of the risk allele had higher HCC risk, with adjusted hazard ratios (95% CI) of 1.88 (1.14-3.10) for rs738409, 1.68 (1.02-2.78) for rs2281135, and 1.61 (0.98-2.67) for rs2235776. This study identified PNPLA3/SAMM50 variants significantly associated with long-term HCC risk in individuals without viral hepatitis. These findings highlight their potential utility as biomarkers for HCC risk stratification and underscore the need for further research into underlying mechanisms. Variants in the PNPLA3/SAMM50 locus were significantly associated with hepatocellular carcinoma (HCC) risk in individuals seronegative for HBsAg and anti-HCV. The stepwise increase in HCC risk with higher numbers of risk alleles suggests their potential utility as biomarkers to identify high-risk individuals without a history of chronic hepatitis B or C virus infection. These findings provide a foundation for genetic risk stratification and precision prevention strategies in populations where non-viral etiologies of HCC are becoming increasingly important.

<sec><title>BACKGROUND</title>Post-TB bronchiectasis is a recognised but under-investigated category of bronchiectasis. This study evaluated its clinical features and identified risk factors for acute exacerbations (AEs).</sec><sec><title>METHODS</title>This retrospective observational cohort study analysed data from the Taiwan Bronchiectasis Registry. Patients with bronchiectasis were included, and those with post-TB bronchiectasis were identified for subgroup analysis. We collected demographics, symptoms, lung function, microbiological data, and modified Reiff scores to assess risk factors for AEs.</sec><sec><title>RESULTS</title>A total of 1,444 patients were analysed, including 222 (15%) with post-TB bronchiectasis. Among them, 54 (24%) experienced at least one AE during the study period. Post-TB bronchiectasis patients had more frequent AEs, higher FACED and modified Reiff scores, lower body mass index (BMI) and forced expiratory volume in 1 s (FEV1), and more symptoms than non-post-TB cases. Post-TB bronchiectasis patients with AEs had higher FACED and Reiff scores, lower BMI and FEV1, and higher rates of positive sputum cultures for gram-negative bacilli (GNB). Multivariable analysis identified FEV1 ≤ 60% predicted (adjusted odds ratio [aOR]: 2.334, 95% CI: 1.192-4.572) and positive GNB cultures (aOR: 3.075, 95% CI: 1.362-6.942) as independent risk factors for AEs.</sec><sec><title>CONCLUSION</title>Post-TB bronchiectasis is associated with a higher risk of exacerbations. Reduced FEV1 and positive GNB cultures are independent risk factors for AEs.</sec>.

Non-neurogenic voiding dysfunction is a bothersome urological condition that has a wide range of causes and limited treatment options. The current study retrospectively analyzed the treatment outcomes of botulinum toxin A (BoNT-A) injection and the predictive factors of successful therapeutic outcomes in women with non-neurogenic voiding dysfunction. This study included women diagnosed with non-neurogenic voiding dysfunction, including dysfunctional voiding (DV), poor relaxation of external sphincter (PRES), bladder neck dysfunction (BND), and detrusor underactivity (DU). Videourodynamic study (VUDS) was performed on all patients before treatment. In total, 100 U of BoNT-A was injected at 5 sites periurethrally in each patient. Treatment outcome was assessed by global response assessment (GRA) to improvement of voiding difficulty at 3 months after treatment. In total, 368 patients received urethral BoNT-A injections. The mean age was 54.1 ± 19.8years. At baseline VUDS, DV was noted in 246 (66.8%) patients, PRES in 112 (30.4%), BND in 5 (1.4%), and DU in 5 (1.4%). The overall success rate by GRA ≥ 2 was 47.8%, including 91.5% in patients with DV, 8.5% in patients with PRES, and none in patients with BND or DU. A higher voiding detrusor pressure (Pdet > 28.5 cmH2O) and a lower post-void residual volume (PVR < 222mL) at baseline could be predictors of successful outcomes after urethral sphincter BoNT-A injections. Urethral sphincter BoNT-A injection is effective in treating non-neurogenic voiding dysfunction caused by DV, but not BND or DU in women. A higher Pdet and a lower PVR at baseline indicate sustainable detrusor contractility and true urethral sphincter dysfunction rather than DU or PRES. Moreover, they may be predictors of a successful therapeutic outcome.

ABSTRACT Herpes zoster is caused by the reactivation of latent varicella-zoster virus (VZV), primarily affecting middle-aged and older individuals and often accompanied by severe pain and other complications. Vaccination is an effective preventive measure against this disease. In the present study, we evaluated the adjuvant activity of Toll-like receptor (TLR)9 and TLR7 agonists in combination with stimulator of interferon genes (STING) agonists for a VZV-glycoprotein E (gE)-based vaccine. Among the tested combinations, the CpG-2722 (TLR9 agonist) and 2′3′-c-di-AM(PS)2 (STING agonist) pairing exhibited potent immunostimulatory activity in immune cells and superior adjuvant activity for VZV-gE vaccines in a mouse models. Shingrix, a licensed herpes zoster vaccine, is administered intramuscularly. The CpG-2722/2′3′-c-di-AM(PS)2 combination adjuvanted VZV vaccine, administered intramuscularly, effectively induced higher gE-specific IgG responses than that induced by the Shingrix and imiquimod/2′3′-c-di-AM(PS)2 adjuvant vaccine. Notably, intranasal administration of the CpG-2722/2′3′-c-di-AM(PS)2 adjuvanted VZV vaccine to mice elicited a robust antigen-specific IgA response, which was barely detectable in intramuscularly administered vaccines. Two doses of the intranasal immunization, administered at a two-week interval, provided long-lasting protection, as antigen-specific IgG levels remained elevated for months without booster immunization. Further investigation into the functional mechanism revealed that CpG-2722 combined with 2′3′-c-di-AM(PS)2 induced a strong antigen-dependent T helper 1 (Th1) cytokine response, consistent with the antigen-independent cytokine-inducing properties of this adjuvant combination. This study demonstrates that the TLR9 and STING agonists formulated adjuvant induces a potent and long-lasting immune response, highlighting its potential as a promising adjuvant candidate for nasal VZV vaccines.

This case report describes the clinical response and safety of intranasal esketamine (Spravato®) in a 61-year-old female with treatment-resistant depression (TRD), a history of electroconvulsive therapy (ECT) poor response, and structural brain abnormalities secondary to left frontal lobe tissue loss from traumatic brain injury in 2008. Despite multiple antidepressant trials, atypical antipsychotic augmentation, and 6 ECT sessions since 2019, the patient achieved only partial remission. In 2024, she received four 56 mg doses of Spravato over 2 weeks while maintaining duloxetine, fluvoxamine, and clozapine therapy. Montgomery-Åsberg Depression Rating Scale (MADRS) scores improved from severe to mild depression, with resolution of suicidal ideation and symptom stabilization. Anxiety symptoms decreased and nightmares ceased post-treatment. Transient dizziness occurred approximately 10 minutes post-administration in all sessions, resolving with 90 minutes of bed rest. No severe adverse events (dissociation, psychosis, or hypertensive crises) were observed. Although limited by an abbreviated treatment regimen and a single-case design, this case suggests that esketamine may be considered in carefully selected TRD patients with structural brain abnormalities and prior ECT poor response, pending validation from larger studies.