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Introduction: This study evaluated the performance of the albumin-lymphocyte-globulin-C-reactive protein (CRP) (ALGC) index as a novel prognostic biomarker for hepatocellular carcinoma (HCC) after hepatectomy., Methods: Patients (n=178) who underwent hepatectomy for HCC (July 2010 - December 2021) were analyzed. The ALGC index was calculated as [(albumin × lymphocyte) / (CRP × globulin × 104)]. Patients were divided into a low ALGC group (<1.82; n=81) and a high ALGC group (≥1.82; n=97). The association of the ALGC index with survival was assessed by univariate and multivariate analyses., Results: The median overall survival (OS) was 100 (range: 1-149) months with 1-, 3-, and 5-year OS rates of 91.6%, 81.2%, and 64.2%, respectively. In univariate analysis, ALGC index (<1.82), alpha-fetoprotein (≥25 ng/mL), tumor size (≥3.5 cm), microvascular invasion, and multiple tumors were associated with shorter OS. ALGC index (<1.82) (hazard ratio [95% confidence interval]) (2.48 [1.407-4.513]; P=0.001) and multiple tumors (1.92 [1.070-3.356]; P=0.029) were independent predictors of OS in multivariate analysis., Conclusion: ALGC index is a novel prognostic biomarker for HCC after hepatectomy. It may assist in treatment stratification and better management of patients with HCC., (S. Karger AG, Basel.)

Background: Sarcopenia accompanied by systemic inflammation is associated with poor prognosis in patients with advanced hepatocellular carcinoma (HCC). However, the effect of sarcopenia combined with systemic inflammation on the prognosis of patients with advanced HCC who underwent hepatectomy is unclear. This study aimed to evaluate the effect of sarcopenia and inflammation on the prognosis of patients with advanced HCC., Methods: This retrospective study included 151 patients recruited between July 2010 and December 2022. We defined advanced HCC as that presenting with vascular invasion or tumor size ≥2 cm or multiple tumors. Sarcopenia was assessed using the psoas muscle index. Preoperative inflammatory markers were used by calculating the prognostic nutritional index, albumin-globulin ratio (AGR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio. Cox regression analysis was performed to determine the prognostic factors for overall survival., Results: Of 151 patients, sarcopenia occurred in 84 (55.6 %). Sarcopenia was significantly associated with male sex, older age, body mass index (<25 kg/m 2 ), and a higher NLR. In the multivariate analysis, AGR <1.25 (hazard ratio [HR], 2.504; 95% confidence interval [CI]: 1.325-4.820; p < 0.05); alpha-fetoprotein levels ≥25 ng/mL (HR, 1.891; 95% CI: 1.016-3.480; p = 0.04); and sarcopenia (HR, 1.908; 95% CI: 1.009-3.776; p < 0.05) were independent predictors of overall survival. The sarcopenia and low AGR groups had significantly worse overall survival than either the non-sarcopenia and high AGR or sarcopenia and low AGR groups., Conclusion: Sarcopenia and AGR are independent prognostic factors in patients with advanced HCC. Thus, sarcopenia may achieve a better prognostic value when combined with AGR., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Background: This study aimed to evaluate the effects of sarcopenia and inflammation on the prognosis of patients with pancreatic cancer after pancreaticoduodenectomy., Methods: Eighty patients who had undergone pancreaticoduodenectomy for pancreatic cancer between July 2010 and December 2023 were included in this study. The psoas muscle index was used to assess sarcopenia. The C-reactive protein-to-albumin ratio, prognostic nutritional index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio were used to calculate the preoperative inflammatory marker levels. The prognostic factors for overall survival were determined using Cox regression analysis., Results: Twenty-four patients were diagnosed with sarcopenia. Sarcopenia showed a significant association with advanced tumor stage. Univariate analysis revealed a significant reduction in overall survival in patients with a prognostic nutritional index of <45, C-reactive protein-to-albumin ratio of ≥0.047, cancer antigen 19-9 levels of ≥130 U/mL, sarcopenia, lymph node metastasis, and vascular invasion. Multivariate analysis revealed that a C-reactive protein-to-albumin ratio of ≥0.047 (hazards ratio, 3.383; 95% confidence interval: 1.384-8.689; p< 0.001), cancer antigen 19-9 levels of ≥130 U/mL (hazards ratio, 2.720; 95% confidence interval: 1.291-6.060; p = 0.008), sarcopenia (hazards ratio, 3.256; 95% confidence interval: 1.535-7.072; p = 0.002) and vascular invasion (hazards ratio, 2.092; 95% confidence interval: 1.057-4.170; p = 0.034) were independent predictors of overall survival. Overall survival in the sarcopenia and high C-reactive protein-to-albumin ratio groups was significantly poorer than that in the non-sarcopenia and low C-reactive protein-to-albumin ratio and sarcopenia or high C-reactive protein-to-albumin ratio groups., Conclusion: Sarcopenia and a high C-reactive protein-to-albumin ratio are independent prognostic factors in patients with pancreatic cancer after pancreaticoduodenectomy. Thus, sarcopenia may have a better prognostic value when combined with the C-reactive protein-to-albumin ratio., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Utsumi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Beta-adrenergic receptors (β-AR) are expressed on the membranes of various cell types and their activation affects body water balance by modulating renal sodium and water excretion, cardiovascular function and metabolic processes. However, β-AR-associated body fluid imbalance has not been well characterised. In the present study, we hypothesized that chronic β-AR stimulation increases electrolyte and water content at the tissue level. We evaluated the effects of isoproterenol, a non-selective β-AR agonist, on electrolyte and water balance at the tissue level. Continuous isoproterenol administration for 14 days induced cardiac hypertrophy, associated with sodium-driven water retention in the heart, increased the total body sodium, potassium and water contents at the tissue level, and increased the water intake and blood pressure of the mice. There was greater urine output in response to the isoproterenol-induced body water retention. These isoproterenol-induced changes were reduced by propranolol, a non-selective beta-receptor inhibitor. Isoproterenol-treated mice even without excessive water intake had higher total body electrolyte and water contents, and this tissue water retention was associated with lower dry body mass, suggesting that β-AR stimulation in the absence of excess water intake induces catabolism and water retention. These findings suggest that β-AR activation induces tissue sodium and potassium retention, leading to body fluid retention, with or without excess water intake. This characterisation of β-AR-induced electrolyte and fluid abnormalities improves our understanding of the pharmacological effects of β-AR inhibitors. Significance Statement We have shown that chronic β-AR stimulation causes cardiac hypertrophy associated with sodium-driven water retention in the heart and increases the accumulation of body sodium, potassium and water at the tissue level. This characterisation of the β-AR-induced abnormalities in electrolyte and water balance at the tissue level improves our understanding of the roles of β-AR in physiology and pathophysiology and the pharmacological effects of β-AR inhibitors., (Copyright © 2024 American Society for Pharmacology and Experimental Therapeutics.)

Purpose: To evaluate the prognostic significance of sarcopenia and systemic inflammatory markers in patients with surgically resected biliary tract cancer (BTC)., Methods: Between July 2010 and December 2022, 146 patients were recruited. Sarcopenia was assessed using the psoas muscle index. Preoperative inflammatory markers were used to calculate the prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio. Cox regression analysis was performed to determine prognostic factors for overall survival (OS) and recurrence-free survival (RFS). P < 0.05 was considered statistically significant., Results: Sixty-four patients had sarcopenia. Sarcopenia was associated with body mass index (< 22 kg/m 2 ), lymph node metastasis, and low PNI (< 42). R1/R2 resection (P = 0.02), sarcopenia (P < 0.001), lymph node metastasis (P = 0.007), intrahepatic cholangiocarcinoma (P < 0.001), and low PNI (P = 0.01) were independent predictors of OS, while male sex (P = 0.04), R1/R2 resection (P < 0.001), lymph node metastasis (P = 0.005), intrahepatic cholangiocarcinoma (P < 0.001), tumor differentiation (other than well; P = 0.003), and low PNI (P = 0.03) were independent predictors of RFS. Patients were stratified into no sarcopenia and high PNI (≥ 42; A), sarcopenia or low PNI (B), and sarcopenia and low PNI (C) groups. Group C had worse OS than the other two groups (P < 0.001 and P = 0.02, respectively)., Conclusion: Sarcopenia is associated with the PNI. Sarcopenia and the PNI are independent prognostic factors among patients with resected BTC. Sarcopenia may have better prognostic value when combined with the PNI., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Renal denervation has attracted attention as a novel antihypertensive treatment for hypertensive patients who are poorly controlled by medicine. Clinical studies have shown the antihypertensive effects of renal denervation in patients with treatment-resistant hypertension. However, renal denervation potentially has other beneficial effects, such as improving glucose metabolism and cardioprotection beyond its antihypertensive effects. In this mini-review article, we summarize and discuss the effects of renal denervation on proteinuria, albuminuria, and renal function based on the recent findings of clinical studies, and review the renoprotective effects of renal denervation., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

We report a case of uterine prolapse in pregnancy, which was successfully managed before delivery. A 35-year-old woman (G2P1) complained consistently of a protruding uterus at 36 weeks gestation, and an engorged uterine cervix without tenderness, urinary disturbance, and incontinence were recognized (Pelvic Organ Prolapse Quantification (POP-Q) score C: +7). Manual retraction of the edematous cervix was gently performed with gauze packing, and strikingly improved edema of the cervix with a POP-Q score of C: -2 was observed one day after the gauze packing. Induction of labor was planned due to a suspected large-for-gestational-age infant, and the patient uneventfully delivered at 39 weeks gestation without any obstacles to delivery and cervical laceration. Cervical edema in pregnancy increases the risk of cervical dystocia and cervical lacerations. However, lacerations with edema are predicted to have a poor wound-healing process. The technique with gauze packing presented in this case may be useful in the protective handling of the uterine cervix during pregnancy., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Tachibana et al.)

Background: Sodium-glucose cotransporter 2 inhibitors are believed to improve cardiac outcomes due to their osmotic diuretic potential., Objectives: The goal of this study was to test the hypothesis that vasopressin-driven urine concentration overrides the osmotic diuretic effect of glucosuria induced by dapagliflozin treatment., Methods: DAPA-Shuttle1 (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment) was a single-center, double-blind, randomized, placebo-controlled trial, in which patients with chronic heart failure NYHA functional classes I/II and reduced ejection fraction were randomly assigned to receive dapagliflozin 10 mg daily or placebo (1:1) for 4 weeks. The primary endpoint was change from baseline in urine osmolyte concentration. Secondary endpoints included changes in copeptin levels and solute free water clearance., Results: Thirty-three randomized, sodium-glucose cotransporter 2 inhibitor-naïve participants completed the study, 29 of whom (placebo: n = 14; dapagliflozin: n = 15) provided accurate 24-hour urine collections (mean age 59 ± 14 years; left ventricular ejection fraction 31% ± 9%). Dapagliflozin treatment led to an isolated increase in urine glucose excretion by 3.3 mmol/kg/d (95% CI: 2.51-4.04; P < 0.0001) within 48 hours (early) which persisted after 4 weeks (late; 2.7 mmol/kg/d [95% CI: 1.98-3.51]; P < 0.0001). Dapagliflozin treatment increased serum copeptin early (5.5 pmol/L [95% CI: 0.45-10.5]; P < 0.05) and late (7.8 pmol/L [95% CI: 2.77-12.81]; P < 0.01), leading to proportional reductions in free water clearance (early: -9.1 mL/kg/d [95% CI: -14 to -4.12; P < 0.001]; late: -11.0 mL/kg/d [95% CI: -15.94 to -6.07; P < 0.0001]) and elevated urine concentrations (late: 134 mmol/L [95% CI: 39.28-229.12]; P < 0.01). Therefore, urine volume did not significantly increase with dapagliflozin (mean difference early: 2.8 mL/kg/d [95% CI: -1.97 to 7.48; P = 0.25]; mean difference late: 0.9 mL/kg/d [95% CI: -3.83 to 5.62]; P = 0.70)., Conclusions: Physiological-adaptive water conservation eliminated the expected osmotic diuretic potential of dapagliflozin and thereby prevented a glucose-driven increase in urine volume of approximately 10 mL/kg/d · 75 kg = 750 mL/kg/d. (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment [DAPA-Shuttle1]; NCT04080518)., Competing Interests: Funding Support and Author Disclosures The DAPA-Shuttle1 study was an investigator-initiated trial funded by AstraZeneca via the externally sponsored scientific research program (ESR-18-13712; Principal Investigator: Dr Titze). The SSIS Project was realized with grant support from Duke-NUS Medical School (Duke-NUS-KBrFA/2019/0026) to Dr Titze. No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Dr Titze has received one personal speaker fee from AstraZeneca in the past 4 years. Dr Greasley has been an employee of and shareholder in AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

2-Deoxy-d-glucose (2DG) induces anticancer effects through glycolytic inhibition but it may raise the risk of arrhythmia. The rare monosaccharide d-allose also has anticancer properties, but its cardiac effects are unknown. We examined the effects of d-allose on adenosine triphosphate (ATP) production in neonatal rat cardiomyocytes. We showed that 25 mM d-allose selectively reduced glycolytic ATP, but had minimal impact on mitochondrial ATP, while 1 mM 2DG strongly inhibited both. Furthermore, d-allose had less impact on cell viability and was less cytotoxic than 2DG; neither compound caused apoptosis. Thus, d-allose selectively diminished glycolytic ATP production with no apparent effects on cardiomyocytes., (Copyright © 2024 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

As a space project, in "Stem Cells" by the Japan Aerospace Exploration Agency (JAXA), frozen mouse ES cells were stored on the International Space Station (ISS) in the Minus Eighty Degree Laboratory Freezer for ISS (MELFI) for 1584 days. After taking these cells back to the ground, the cells were thawed and cultured, and their gene expressions were comprehensively analyzed using RNA sequencing in order to elucidate the early response of the cells to long-time exposure to space radiation consisting of various ionized particles. The comparisons of gene expression involved in double-stranded break (DSB) repair were examined. The expressions of most of the genes that were involved in homologous recombination (HR) and non-homologous end joining (NHEJ) were not significantly changed between the ISS-stocked cells and ground-stocked control cells. However, the transcription of Trp53inp1 (tumor protein 53 induced nuclear protein-1), Cdkn1a (p21), and Mdm2 genes increased in ISS-stocked cells as well as Fe ion-irradiated cells compared to control cells. This suggests that accumulated DNA damage caused by space radiation exposure would activate these genes, which are involved in cell cycle arrest for repair and apoptosis in a p53-dependent or -independent manner, in order to prevent cells with damaged genomes from proliferating and forming tumors.

Background/aim: Sarcopenia accompanied by systemic inflammation is associated with poor prognosis in patients with cancer. This study evaluated the prognostic significance of sarcopenia (myopenia and myosteatosis) and systemic inflammatory markers in older patients (aged ≥80 years) with resected biliary tract cancer., Patients and Methods: Patients who underwent resection for biliary tract cancer between July 2010 and January 2023 at the NHO Fukuyama Medical Center were retrospectively reviewed. Preoperative computed tomography measured myopenia and myosteatosis, using the psoas muscle index and modified intramuscular adipose tissue content. Associations between clinicopathological characteristics, inflammation-based prognostic scores, and overall survival were analyzed using Cox proportional hazards models., Results: Univariate analysis revealed low C-reactive protein-to-albumin ratio (<0.125), low prognostic nutritional index (<42), low modified intramuscular adipose tissue content, higher T-stage (T3-4), lymph node metastasis, and postoperative complications associated with worse overall survival in older patients (aged ≥ 80 years) with resected biliary tract cancer (n=48). Multivariate analysis identified low prognostic nutritional index (<42) (p=0.007), low modified intramuscular adipose tissue content (p=0.015), higher T-stage (T3-4) (p<0.001), lymph node metastasis (p=0.001), and postoperative complications (p=0.017) as independent predictors of overall survival., Conclusion: Preoperative myosteatosis and low prognostic nutritional index are independent prognostic factors for overall survival in older patients (aged ≥80 years) with resected biliary tract cancer. These factors may be useful for risk stratification and clinical decision-making. Early interventions, such as nutritional support and physical exercise, may improve outcomes after resection of biliary tract cancer., Competing Interests: The Authors declare that they have no competing interests., (Copyright 2024, International Institute of Anticancer Research.)

Previous basic and clinical investigations have identified various pathogenic factors and determinants of risk that contribute to hypertension. Nevertheless, the pathogenesis of hypertension has not been fully elucidated. Moreover, despite the availability of antihypertensive medications for the management of blood pressure, treatments that address the full spectrum of the pathophysiological defects underpinning hypertension remain to be identified. To further investigate the mechanisms of primary hypertension, it is imperative to consider novel potential aspects, such as fluid management by the skin, in addition to the conventional risk factors. There is a close association between body fluid regulation and blood pressure, and the kidney, which, as the principal organ responsible for body fluid homeostasis, is the primary target for research in the field of hypertension. In addition, the skin functions as a biological barrier, potentially contributing to body fluid regulation. In this review, we propose the hypothesis that changes in skin water conservation are associated with hypertension risk based on recent findings. Further studies are required to clarify whether this novel hypothesis is limited to specific hypertension or applies to physiological blood pressure regulation., Competing Interests: Disclosures None

Renal denervation (RDN) has emerged as a novel therapy for drug-resistant hypertension. We here examined the effects of RDN at early versus advanced stages of hypertension on blood pressure and organ pathology in rats with salt-sensitive hypertension. Dahl salt-sensitive (DahlS) rats fed an 8% NaCl diet from 6 weeks of age were subjected to RDN (surgical ablation and application of 10% phenol in ethanol) or sham surgery at 7 (early stage) or 9 (advanced stage) weeks and were studied at 12 weeks. RDN at early or advanced stages resulted in a moderate lowering of blood pressure. Although RDN at neither stage affected left ventricular (LV) and cardiomyocyte hypertrophy, it ameliorated LV diastolic dysfunction, fibrosis, and inflammation at both stages. Intervention at both stages also attenuated renal injury as well as downregulated the expression of angiotensinogen and angiotensin-converting enzyme (ACE) genes and angiotensin II type 1 receptor protein in the kidney. Furthermore, RDN at both stages inhibited proinflammatory gene expression in adipose tissue. The early intervention reduced both visceral fat mass and adipocyte size in association with downregulation of angiotensinogen and ACE gene expression. In contrast, the late intervention increased fat mass without affecting adipocyte size as well as attenuated angiotensinogen and ACE gene expression. Our results thus indicate that RDN at early or late stages after salt loading moderately alleviated hypertension and substantially ameliorated cardiac and renal injury and adipose tissue inflammation in DahlS rats. They also suggest that cross talk among the kidney, cardiovascular system, and adipose tissue may contribute to salt-sensitive hypertension. Supposed mechanism for the beneficial effects of RDN on hypertension and target organ damage in DahlS rats. RDN at early or late stages after salt loading moderately alleviated hypertension and substantially ameliorated renal injury in DahlS rats. Cross talk among the kidney, cardiovascular system, and adipose tissue possibly mediated by circulating RAS may contribute to salt-sensitive hypertension. LV; left ventricular, NE; norepinephrine, RAS; renin-angiotensin system, RDN; renal denervation., (© 2024. The Author(s).)

Total 276 manuscripts were published in Hypertension Research in 2022. Here our editorial members picked up the excellent papers, summarized the current topics from the published papers and discussed future perspectives in the sixteen fields. We hope you enjoy our special feature, 2023 update and perspectives in Hypertension Research., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)