Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide with a poor prognosis. Treatment with immune checkpoint inhibitors (ICIs) has improved overall survival in patients with HCC. However, not all patients benefit from the treatment. In this study, 59 patients with HCC were enrolled from two medical centers in Saudi Arabia, with 34% using antibiotics concurrently with their Nivolumab (anti-PD1 blockade). The impact of antibiotic use on the clinical outcomes of patients with HCC undergoing treatment with anti-PD1 blockade was examined. The patients' overall survival (OS) was 5 months (95% CI: 3.2, 6.7) compared to 10 months (95% CI: 0, 22.2) (p = 0.08). Notably, patients with Child-Pugh A cirrhosis receiving anti-PD1 blockade treatment without concurrent antibiotic use showed a significantly longer median OS reaching 22 months (95% CI: 6.5, 37.4) compared to those who were given antibiotics with a median OS of 6 months (95% CI: 2.7, 9.2) (p = 0.02). This difference in overall survival was particularly found in Child-Pugh class A patients receiving anti-PD1 blockade. These findings suggest that antibiotic use may negatively affect survival outcomes in HCC patients undergoing anti-PD1 blockade, potentially due to antibiotic-induced alterations to the gut microbiome impacting the anti-PD1 blockade response. This study suggests the need for careful consideration when prescribing antibiotics to patients with HCC receiving anti-PD1 blockade.
Background Sepsis remains a major cause of death, with high mortality and morbidity rates in children. The cause of mortality may be associated with several factors, including differences in cultures and the type of organism. This study was aimed at evaluating the characteristics and outcomes of negative bacterial blood culture compared to those of positive bacterial blood culture in children with severe sepsis/septic shock. Methods A retrospective cohort study was conducted at a pediatric intensive care unit (PICU) of a tertiary care medical center. All pediatric patients, from newborn to 14 years of age, admitted between April 2015 and January 2018 were included in the study if they fulfilled the criteria for severe sepsis/septic shock. Results Of the 209 patients, 30 (14.3%) had a positive bacterial blood culture whereas 179 (86.6%) had a negative bacterial blood culture. Mortality was more in positive bacterial blood culture 13 (43%) vs 35 (20%) in negative bacterial blood culture (P = 0.004). Respiratory tract infections were extremely common, present in 108 of 179 (60%) patients, and tended to result in a negative culture. The rate of organ dysfunction was higher in the positive bacterial blood culture group at admission (P = 0.01). However, the results did not reveal a significant finding related to multiorgan dysfunction syndrome (MODS) progression over three days of PICU admission (P = 0.06). Conclusion The negative bacterial blood culture constitutes a substantial proportion of pediatric patients with severe sepsis/septic shock. Furthermore, these pediatric patients have a lower mortality rate compared to positive bacterial blood cultures. The culture-negative sepsis group also had less organ dysfunction.
