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824; sensitivity 75.9%; specificity 80.0%). CONCLUSIONS The combination of multiple markers of host-derived inflammation and tumor-derived focal hypermetabolism can serve as a predictor for the presence of HGD/INV.PURPOSE We aimed to evaluate the prognostic impact of pulmonary dysfunctions and their relationships with other possible prognostic factors, especially sarcopenia, in elderly patients with gastric carcinoma (GC). METHODS In total, 402 elderly GC patients (≥ 75 years) who underwent radical gastrectomy were retrospectively reviewed. Restrictive and obstructive pulmonary dysfunction were defined as %VC less then 80% and FEV1.0% less then 70%, respectively. RESULTS Forty-two patients (10.4%) had a low %VC, which was associated with ASA-PS, comorbidity and sarcopenia while correlating with neither the FEV1.0% nor pathological variables. The overall survival in the low %VC group was significantly worse than that in the high %VC group, especially in those with pStage I/II diseases. The survival was not stratified by FEV1.0%. Non-gastric cancer-related deaths were more prevalent in the low %VC group than in the high %VC group. The cancer-specific survival showed no significant differences between the two groups. A multivariate analysis revealed a low %VC to be the most powerful predictor of a poor survival among all independent variables, including sex, age, comorbidity, total gastrectomy, and pStage. Patients with both a low %VC and sarcopenia showed an extremely poor survival. CONCLUSIONS Preoperative restrictive pulmonary dysfunction was independently associated with poor survival outcomes, especially when present in combination with sarcopenia, due to an increased risk of death from non-cancer-related causes.PURPOSE An association between the prognoses of trauma and sarcopenia has not been well documented. Bemcentinib The purpose of this study was to compare the outcomes of elderly Japanese trauma patients with sarcopenia and those without sarcopenia. METHODS The medical records of patients aged ≧ 65 years old and Injury Severity Scores above 15 treated for trauma between 2010 and 2017 were reviewed, retrospectively. We measured the psoas muscle index (PMI), defined as the psoas muscle area at the third lumbar vertebra level divided by the body surface area. Patients of each gender with a PMI less than the lower interquartile range were included in the sarcopenia group. A questionnaire was mailed to the patients or their families to collect data on 1-year mortality and activities of daily living. RESULTS There were 405 patients included in this study 304 in the non-sarcopenia group (Group NS) and 101 in the sarcopenia group (Group S). Mortality was significantly higher in Group S than in Group NS (NS; 7.9% vs. S; 15.8%, OR, 2.20; 95% CI, 1.12-4.32; p = 0.027). Only 175 of the questionnaires were completed and the responses did not reveal any significant differences between the groups. CONCLUSIONS Sarcopenia as defined by the PMI may be used as an indicator for mortality risk for geriatric trauma patients.PURPOSE Cyclocreatine, a creatine analog, is a candidate drug for treating patients with cerebral creatine deficiency syndromes (CCDSs) caused by creatine transporter (CRT, SLC6A8) deficiency, which reduces brain creatine level. The purpose of this study was to clarify the characteristics of cyclocreatine transport in HEK293 cells, which highly express endogenous CRT, in hCMEC/D3 cells, a human blood-brain barrier (BBB) model, and in CCDSs patient-derived fibroblasts with CRT mutations. METHODS Cells were incubated at 37°C with [14C]cyclocreatine (9 μM) and [14C]creatine (9 μM) for specified periods of times in the presence or absence of inhibitors, while the siRNAs were transfected by lipofection. Protein expression and mRNA expression were quantified using targeted proteomics and quantitative PCR, respectively. RESULTS [14C]Cyclocreatine was taken up by HEK293 cells in a time-dependent manner, while exhibiting saturable kinetics. The inhibition and siRNA knockdown studies demonstrated that the uptake of [14C]cyclocreatine by both HEK293 and hCMEC/D3 cells was mediated predominantly by CRT as well as [14C]creatine. In addition, uptake of [14C]cyclocreatine and [14C]creatine by the CCDSs patient-derived fibroblasts was found to be largely reduced. CONCLUSION The present study suggests that cyclocreatine is a CRT substrate, where CRT is the predominant contributor to influx of cyclocreatine into the brain at the BBB. Our findings provide vital insights for the purposes of treating CCDSs patients using cyclocreatine.BACKGROUND Liver injury induced by immune checkpoint inhibitors (ICIs) is an immune-related adverse event (irAE) whose incidence has increased with the broader use of ICIs in clinical practice. However, the incidental risk factors of immune-related liver injury are unknown. We investigated the clinical characteristics of immune-related liver injury. METHODS A total of 546 patients treated with ICIs for advanced malignancies between September 2014 and February 2019 were included retrospectively. Factors associated with immune-related liver injury were determined. RESULTS Immune-related liver injury (≥ Grade 3) occurred in 29 (5.3%) patients (Grade 3, n = 20; Grade 4, n = 8; Grade 5, n = 1) during the follow-up period (median 153 days). The patterns of liver injuries were hepatocellular, n = 6 (20.7%); cholestatic, n = 17 (58.6%); and mixed, n = 6 (20.7%). The median period between the initial administration of ICIs and the incidence of irAEs was 52 days. Of 29 patients with immune-related liver injury (≥ Grade 3), four showed immune-related cholangitis with non-obstructive dilation of the bile ducts. Factors that were significantly associated with the incidence of immune-related liver injury in multivariate analysis were use of ipilimumab, anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) agent [hazard ratio [HR] 4.22, 95% confidence interval (CI) 1.65-10.80, P = 0.003], and fever over 38 °C within 24 h of initial ICI administration (HR 6.21, 95% CI 2.68-14.40, P less then 0.001). CONCLUSIONS We found that the use of ipilimumab and the presence of fever within 24 h of initial ICI administration were predictive factors for immune-related liver injury.
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