Immune checkpoint inhibitors (ICIs) belong to the therapeutic armamentarium in advanced hepatocellular carcinoma (HCC). However, only a minority of patients benefit from immunotherapy. Therefore, we aimed to identify indicators of therapy response. This multicenter analysis included 99 HCC patients. Progression-free (PFS) and overall survival (OS) were studied by Kaplan-Meier analyses for clinical parameters using weighted log-rank testing. Next-generation sequencing (NGS) was performed in a subset of 15 patients. The objective response (OR) rate was 19% median OS (mOS)16.7 months. Forty-one percent reached a PFS > 6 months; these patients had a significantly longer mOS (32.0 vs. 8.5 months). Child-Pugh (CP) A and B patients showed a mOS of 22.1 and 12.1 months, respectively. Ten of thirty CP-B patients reached PFS > 6 months, including 3 patients with an OR. Tumor mutational burden (TMB) could not predict responders. Of note, antibiotic treatment within 30 days around ICI initiation was associated with significantly shorter mOS (8.5 vs. 17.4 months). Taken together, this study shows favorable outcomes for OS with low AFP, OR, and PFS > 6 months. No specific genetic pattern, including TMB, could identify responders. Antibiotics around treatment initiation were associated with worse outcome, suggesting an influence of the host microbiome on therapy success.

Objectives: To assess the association between country income status and national prevalence of invasive infections caused by the top-ranked bacteria on the WHO priority list: carbapenem-resistant (CR) Acinetobacter spp., Klebsiella spp. and Pseudomonas aeruginosa; third-generation cephalosporin-resistant (3GCR) Escherichia coli and Klebsiella spp.; and MRSA and vancomycin-resistant Enterococcus faecium (VR E. faecium). Methods: Active surveillance systems providing yearly prevalence data from 2012 onwards for the selected bacteria were included. The gross national income (GNI) per capita was used as the indicator for income status of each country and was log transformed to account for non-linearity. The association between antibiotic prevalence data and GNI per capita was investigated individually for each bacterium through linear regression. Results: Surveillance data were available from 67 countries: 38 (57%) were high income, 16 (24%) upper-middle income, 11 (16%) lower-middle income and two (3%) low income countries. The regression showed significant inverse association (P<0.0001) between resistance prevalence of invasive infections and GNI per capita. The highest rate of increase per unit decrease in log GNI per capita was observed in 3GCR Klebsiella spp. (22.5%, 95% CI 18.2%–26.7%), CR Acinetobacter spp. (19.2% 95% CI 11.3%–27.1%) and 3GCR E. coli (15.3%, 95% CI 11.6%–19.1%). The rate of increase per unit decrease in log GNI per capita was lower in MRSA (9.5%, 95% CI 5.2%–13.7%). Conclusions: The prevalence of invasive infections caused by the WHO top-ranked antibiotic-resistant bacteria is inversely associated with GNI per capita at the global level. Public health interventions designed to limit the burden of antimicrobial resistance should also consider determinants of poverty and inequality, especially in lower-middle income and low income countries.

Molecular Tumor Boards (MTBs) are pivotal in personalized cancer care. This systematic review and meta-analysis included 34 studies out of 576 articles (2020–January 2024) involving 12,176 patients across 26 major cancer entities. Of these, 20.8% (2,532 patients) received MTB-recommended therapies, with 178 outcome measures reported, achieving a median overall survival (OS) of 13.5 months, progression-free survival (PFS) of 4.5 months, and an objective response rate (ORR) of 5–57%. A pooled PFS2/PFS1 ratio ≥ 1.3 from 14 reports was observed in 38% (33–44%) of cases. Comparative data showed improved outcomes for MTB-treated patients, with hazard ratios of 0.46 (0.28–0.76, p < 0.001) for OS in 19 and 0.65 (0.52–0.80, p < 0.001) for PFS in 3 studies. These results highlight the benefits of MTB evaluations in improving outcomes for patients with solid tumors but also emphasize the need for standardized evaluation criteria to enable robust comparisons across studies.

The burden of infection in communities determines the spread of rotavirus infection and disease in susceptible populations. This study reports rotavirus infection and disease in a community based birth cohort in Vellore. Bimonthly surveillance and diarrheal stool were collected from 452 children enrolled at birth, of whom 373 completed three years of follow up. Samples were screened for rotavirus by an ELISA and genotyped by reverse transcription polymerase chain reaction for VP7 and VP4 genes. Rotavirus incidence rates were calculated using Poisson regression equations. Risk factors associated with symptomatic and asymptomatic rotavirus infections were compared using multiple logistic regression. A total of 1149 episodes of rotavirus infections occurred in 94.4% children in the cohort. Incidence of rotavirus infection was 1.04 (0.97-1.1) per child-year with 0.75 asymptomatic and 0.29 symptomatic infections per child-year. About 18% of the children were infected in the first month, mainly with the G10P[11] strain. Rotavirus infections were more prevalent during October-March, but seasonality was not as marked in rotavirus disease. Rotavirus was associated with 15.1% of mild diarrhea, 38.9% of moderate/severe diarrhea and 66.7% of very severe diarrhea. Four common G types - G1 (26.8%), G2 (16%), G10 (11.2%) and G9 (9.6%) were seen, with high rates of mixed infections and untypable samples. Male gender, presence of siblings and low maternal education were associated with rotavirus disease. This study demonstrates that rotavirus is the most common cause of gastroenteritis in the community, and indicates that since rotavirus caused the greatest proportion of moderate and severe disease, targeted interventions such as vaccines are needed for rotavirus, in addition to health education, sanitation and appropriate treatment to decrease diarrheal disease in communities.

Background/Objectives: While antibiotic prophylaxis is crucial for preventing infections, its impact on the development of antibiotic-resistant infections and clinical outcomes remains underexplored. We aimed to systematically assess the impact of medical and surgical antibiotic prophylaxis (SAP) on the development of antibiotic-resistant infections, clinical outcomes, and costs. Methods: A systematic review and meta-analysis of the effect of antibiotic prophylaxis on antibiotic-resistant infections, mortality, length of hospital stay, and/or costs was conducted in hemato-oncological or surgical patient populations. Pooled estimates of the relative risk (RR) or weighted mean difference (WMD) were derived using random-effect meta-analysis. Results: Of 10,409 screened studies, 109 (30%) comprising 131,519 patients were included. In 55 hemato-oncological studies, prophylaxis significantly reduced Gram-negative infections (RR: 0.51; 95% CI: 0.45 to 0.59) without an effect on mortality (RR = 1.01; 95% CI: 0.89 to 1.15), while the risk of developing an infection resistant to prophylactic antibiotics during hospitalization was doubled (RR: 2.05; 95% CI: 1.88 to 2.23). The length of hospitalization was reduced by 1.85 days. Among 54 surgical studies, SAP lowered surgical-site infections (RR: 0.58; 95% CI: 0.49 to 0.69). Extending prophylaxis beyond the recommended duration did not improve infection rates (RR: 1.10; 95% CI: 0.98 to 1.24). No association was demonstrated between prophylaxis adjusted by colonization status and the development of resistant infections. Conclusion: Though proven beneficial, our results highlight the critical need for targeted antibiotic stewardship programs (ASPs) in both settings. A meticulous risk assessment balancing the benefits of preventing life-threatening infections against the risk of driving antimicrobial resistance, and a tailored ASP, is urgently needed for hemato-oncological patients.

SUMMARY: Asymptomatic enteric infections are important where sequelae or protection from subsequent illness is an outcome measure. The use of reverse transcription–polymerase chain reaction (RT–PCR) to identify asymptomatic enteric infections in a birth cohort followed for rotaviral infections in a south Indian urban slum is reported. Of 1191 non-diarrhoeal samples from 371 children collected in May–June 2003, 22 (1·9%) were positive by ELISA. A total of 147 (40·6%) of 362 samples tested by VP6 RT–PCR were positive. In those samples that could be typed, a high diversity of G types including G1, G2, G4, G8, G9 and G10, and a high proportion (34·4%) of mixed infections were detected. Noroviruses were identified in 6/28 (21·4%) samples tested. The identification of infections undetectable by conventional techniques indicates the importance of the use of sensitive diagnostic techniques in research studies. Asymptomatically infected children may also act as a source of infection for other susceptible hosts.