Calf Circumference as an Indicator for Cystatin C Testing in Hospitalized Elderly Male Patients for Detecting Hidden Renal Impairment.

Serum creatinine is used to measure the estimated glomerular filtration rate (eGFR); however, it is influenced by muscle mass and may therefore overestimate renal function in patients with sarcopenia. We examined calf circumference (CC) as a convenient muscle mass evaluation tool that can potentially indicate the need to test for cystatin C instead of creatinine in elderly inpatients. We retrospectively reviewed the electronic health record of 271 inpatients aged 65 or over. CC was determined by measuring the thickest part of the nondominant calf. eGFRcys and eGFRcr were calculated using cystatin C and creatinine levels, respectively. We evaluated optimum CC cutoff values using the eGFRcys/eGFRcr ratio for detecting hidden renal impairment (HRI, defined as eGFRcr ≥ 60 mL/min/1.73 m2 but eGFRcys < 60 mL/min/1.73 m2). CC showed a significant positive correlation with the eGFRcys/eGFRcr ratio in both sexes. The areas under the receiver operating characteristic curve were 0.725 and 0.681 for males and females, respectively. CC cutoffs with a sensitivity or specificity of 90% or 95% might be used to detect HRI in males. In conclusion, utilizing the optimum cutoff, CC could be a cost-effective screening tool for detecting HRI in elderly male patients using cystatin C as an add-on test.

Association of Tim-3/Gal-9 Axis with NLRC4 Inflammasome in Glioma Malignancy: Tim-3/Gal-9 Induce the NLRC4 Inflammasome.

Tim-3/Gal-9 and the NLRC4 inflammasome contribute to glioma progression. However, the underlying mechanisms involved are unclear. Here, we observed that Tim-3/Gal-9 expression increased with glioma malignancy and found that Tim-3/Gal-9 regulate NLRC4 inflammasome formation and activation. Tim-3/Gal-9 and NLRC4 inflammasome-related molecule expression levels increased with WHO glioma grade, and this association was correlated with low survival. We investigated NLRC4 inflammasome formation by genetically regulating Tim-3 and its ligand Gal-9. Tim-3/Gal-9 regulation was positively correlated with the NLRC4 inflammasome, NLRC4, and caspase-1 expression. Tim-3/Gal-9 did not trigger IL-1ß secretion but were strongly positively correlated with caspase-1 activity as they induced programmed cell death in glioma cells. A protein-protein interaction analysis revealed that the FYN-JAK1-ZNF384 pathways are bridges in NLRC4 inflammasome regulation by Tim-3/Gal-9. The present study showed that Tim-3/Gal-9 are associated with poor prognosis in glioma patients and induce NLRC4 inflammasome formation and activation. We proposed that a Tim-3/Gal-9 blockade could be beneficial in glioma therapy as it would reduce the inflammatory microenvironment by downregulating the NLRC4 inflammasome.

Clinical Significance of Glycolytic Metabolic Activity in Hepatocellular Carcinoma.

High metabolic activity is a hallmark of cancers, including hepatocellular carcinoma (HCC). However, the molecular features of HCC with high metabolic activity contributing to clinical outcomes and the therapeutic implications of these characteristics are poorly understood. We aimed to define the features of HCC with high metabolic activity and uncover its association with response to current therapies. By integrating gene expression data from mouse liver tissues and tumor tissues from HCC patients (n = 1038), we uncovered three metabolically distinct HCC subtypes that differ in clinical outcomes and underlying molecular biology. The high metabolic subtype is characterized by poor survival, the strongest stem cell signature, high genomic instability, activation of EPCAM and SALL4, and low potential for benefitting from immunotherapy. Interestingly, immune cell analysis showed that regulatory T cells (Tregs) are highly enriched in high metabolic HCC tumors, suggesting that high metabolic activity of cancer cells may trigger activation or infiltration of Tregs, leading to cancer cells' evasion of anti-cancer immune cells. In summary, we identified clinically and metabolically distinct subtypes of HCC, potential biomarkers associated with these subtypes, and a potential mechanism of metabolism-mediated immune evasion by HCC cells.

Risk factors of incisional hernia after single-incision cholecystectomy and safety of barbed suture material for wound closure.

Purpose: Single-incision cholecystectomy is a surgical method that offers comparable results to conventional laparoscopic cholecystectomy. However, a high risk of postoperative incisional hernia is an issue in single-incision cholecystectomy. This study evaluated the risk factors and incidences of incisional hernia after single-incision cholecystectomy and the advantage issue of using barbed suture material during wound closures. Methods: A total of 1,111 patients underwent laparoscopic or robotic single-incision cholecystectomy between March 2014 and February 2020 at our institution at CHA Bundang Medical Center. During this period, there were 693 patients who underwent wound closure with monofilament suture material (Monosyn 2-0; B. Braun) and the other 418 patients used barbed suture material (Stratafix 2-0; Ethicon). Results: The two patient groups were comparable in age, body mass index, and diagnosis. The total incidence of incisional hernia after single-incision cholecystectomy was 0.5% (five cases). All patients who developed incisional hernia were in the monofilament suture material group (0.7% vs. 0%, p = 0.021). The influence of predictive and possible risk factors on incisional hernia rate was analyzed. Among these factors, only old age was an independent predictive risk factor of incisional hernia. Conclusion: Our study showed a low incidence of incisional hernia, all of which occurred in the monofilament suture material group. If technically appropriate, single-incision cholecystectomy does not appear to present a high incidence of hernia. Barbed suture material can be safely applied in wound closure showing comparable incisional hernia incidence to monofilament suture material.