Himeji Red Cross Hospital

Background: Gastrointestinal immune-related adverse events (GI-irAEs) are recognized complications of immune checkpoint inhibitors (ICIs), but their prognostic relevance and associated risk factors remain unclear. This study aimed to assess whether baseline nutritional status, measured using the prognostic nutritional index (PNI), modifies the prognostic impact of GI-irAEs, and to identify clinical factors associated with their occurrence. Methods: We retrospectively analyzed 1104 cancer patients treated with ICIs at a single institution. GI-irAEs were defined as gastrointestinal symptoms requiring clinical intervention. Patients were stratified by irAE type and PNI (≥40 vs. <40), and differences in survival and treatment response were evaluated. Potential risk factors for developing GI-irAEs were also examined. Results: GI-irAEs occurred in 2.7% of patients and were associated with prolonged overall survival (median: 28.7 vs. 14.0 months) among those with PNI ≥ 40. This survival advantage was not observed in patients with PNI < 40. The PNI-dependent prognostic pattern was specific to GI-irAEs and not observed for non-GI irAEs. Similar trends were confirmed in 4- and 8-week landmark analyses. Differences in objective response rate and disease control rate by PNI status were most pronounced in patients with GI-irAEs. The use of anti-CTLA-4 antibodies was significantly associated with GI-irAE development (odds ratio 4.24; 95% confidence interval 1.73-10.39). Conclusions: GI-irAEs appear to confer a survival benefit primarily in patients with preserved nutritional status. PNI may serve as a useful tool to contextualize the clinical relevance of GI-irAEs and help identify patients most likely to benefit from immune activation during ICI therapy.

Background/Objective: Recently, there has been an increasing need to implement the diagnosis of the presence of covert hepatic encephalopathy (CHE) in patients with cirrhosis. The aim of this study was to identify novel factors associated with CHE in clinical practice. Methods: This retrospective study enrolled a total of 402 patients with cirrhosis at 17 institutions. The Stroop test was performed to diagnose CHE at each center. Results: The patients comprised 233 males and 169 females, with a median age of 69 (IQR, 61-75) years. The median albumin and 25(OH)D3 levels were 3.9 (3.5-4.3) g/dL and 15.4 (11.0-21.0) ng/mL, respectively. This cohort included 181 patients with esophageal varices (EV). Multivariate analysis revealed that low 25(OH)D3 (p < 0.05) and EV (p < 0.05) were independent risk factors for CHE. When limited to only laboratory factors, low albumin (p < 0.01) and low 25(OH)D3 (p < 0.05) were independent factors for CHE. The optimal cut-off values of albumin and 25(OH)D3 for predicting CHE were 3.7 g/dL and 16.5 ng/mL, respectively. The prevalence of CHE was 59.2% for 25(OH)D3 < 16.5 ng/mL and EV, 53.8% for albumin < 3.7 g/dL and 25(OH)D3 < 16.5 ng/mL, and 66.7% for albumin < 3.7 g/dL, EV, and 25(OH)D3 < 16.5 ng/mL. Conclusions: Low 25(OH)D3 and albumin levels, and the EV were positively associated with CHE in patients with cirrhosis. Specifically, the prevalence of CHE increased with a decrease in 25(OH)D3 levels. Patients with such risk factors should be actively and carefully examined for the presence of CHE.

Acute encephalopathy is a severe condition predominantly affecting children with viral infections. The purpose of this study was to elucidate the epidemiology, treatment, and management of acute encephalopathy. The study also aimed to understand how the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has affected epidemiological trends. This retrospective study used the database of the Febrile Acute Convulsion and Encephalopathy registry, a prospective multicenter consecutive case registry for acute encephalopathy and febrile convulsive status epilepticus. Pediatric patients aged 0-18years hospitalized and diagnosed with acute encephalopathy between January 2020 and August 2023 were included in this study. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) was the most common syndrome (36 cases, 27.5%). SARS-CoV-2 was the most common pathogen (19 cases, 14.5%), followed by influenza virus type A (15 cases, 11.5%). Targeted temperature management was performed for 25 (69.4%) of 36 patients with AESD; 5 (50.0%) of 10 patients with hemorrhagic shock and encephalopathy; and only 1 (5.9%) of 17 patients with mild encephalitis or encephalopathy with a reversible splenial lesion (MERS). High-dose corticosteroids were administered to 9 (90.0%) of 10 patients with hemorrhagic shock and encephalopathy and 11 (30.6%) of 36 patients with AESD. The primary causative pathogen of acute encephalopathy has changed to SARS-CoV-2. AESD remains the most common syndrome. Targeted temperature management is more, whereas high-dose corticosteroid therapy is less, frequently used. No specific treatment for mild encephalitis or encephalopathy with a reversible splenial lesion has been established.

We investigated the impact of proteinuria on the therapeutic effect before lenvatinib administration as second-line treatment after atezolizumab-bevacizumab. We examined 64 patients who were administered lenvatinib as second-line treatment after discontinuation of atezolizumab and bevacizumab. Proteinuria assessed before lenvatinib administration was considered severe if the qualitative value test (QV) was 3+ or the urine protein/creatinine ratio (UPCR) was ≥ 2.0 (group A, n = 13) and non-severe if the UPCR was < 2.0 or the QV was ≤ 2+ (group B, n = 51). In the entire cohort, the modified albumin-bilirubin grades were grades 1, 2a, 2b, and 3 in 12, 21, 26, and 5 patients, respectively. Regarding the Barcelona Clinic of Liver Cancer stage, 2, 22, and 40 patients had stages A, B, and C, respectively. The objective response rate (ORR) was 14.0% and the disease control rate (DCR) was 59.3%. The median survival time and progression free survival after administration of lenvatinib was 14.8 (95% confidence interval [CI], 11.3-18.4) and 5.5 (95% CI, 3.6-7.5) months, respectively. The ORR and DCR were 0% and 38.4% for group A (n = 13) and 17.6% and 64.7% for group B (n = 51), respectively. The median time to treatment failure was 2.2 months in group A and 4.2 months in group B (p = 0.120). Severe proteinuria before lenvatinib as a second-line therapy after atezolizumab-bevacizumab treatment may affect the duration of lenvatinib administration and treatment efficacy.

Background and aims Endoscopic mucosal resection (EMR) is a standard preventive method for colorectal cancer. Managing patients on anticoagulants during EMR is challenging because of balancing bleeding and thrombotic risks. Updated guidelines recommend continuing anticoagulants over heparin bridging; however, data on bleeding risks with continuing anticoagulants remain limited. This multicenter prospective study evaluated bleeding rates in patients who continued oral anticoagulants during EMR. Methods Patients on warfarin or direct oral anticoagulants (DOACs) undergoing EMR were enrolled from 12 tertiary hospitals. Warfarin was maintained on the day of EMR, while DOACs were paused on the day of EMR and resumed afterward. Post-EMR mucosal defects were closed with clips per protocol. Adverse events were monitored for 30 days. The primary endpoint was the major bleeding rate, defined as immediate bleeding requiring difficult hemostasis or delayed bleeding necessitating endoscopic intervention. The secondary endpoints were minor bleeding, other adverse events, and differences in bleeding rates between warfarin and DOACs. Results Among 107 patients (341 polyps; mean size = 6.7 mm), major bleeding occurred in five (4.7%) patients (95% confidence interval: 2.0%-10.5%), and all cases were managed endoscopically. Minor bleeding and thromboembolism events occurred in eight (7.5%)patients and one (0.9%) patient, respectively. No significant differences in bleeding rates were observed between warfarin and DOACs. Major bleeding rates were lower than those reported for heparin bridging. Conclusions Continuing anticoagulanttherapy during EMR was associated with a low major bleeding rate (4.7%) and minimal thrombotic events, supporting its safety as an alternative to heparin bridging.