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A research letter published in the journal Circulation discusses the LMNA Q353R mutation, which is associated with dilated cardiomyopathy. The mutation causes DNA damage accumulation in the heart, leading to premature aging and poor prognosis. The study found that vitamin D2 showed efficacy in reducing DNA damage in patient-specific cardiomyocytes. Another study investigated the mechanism by which the mutation causes DNA damage and found that abnormal localization of the vitamin D receptor leads to reduced DNA repair. The intervention with vitamin D2 can reduce DNA damage and improve cardiac function. This research provides insights into potential treatments for LMNA-mutant cardiomyopathy using vitamin D. [Extracted from the article]

BACKGROUND: The heart comprises many types of cells such as cardiomyocytes, endothelial cells (ECs), fibroblasts, smooth muscle cells, pericytes, and blood cells. Every cell type responds to various stressors (eg, hemodynamic overload and ischemia) and changes its properties and interrelationships among cells. To date, heart failure research has focused mainly on cardiomyocytes; however, other types of cells and their cell-to-cell interactions might also be important in the pathogenesis of heart failure. METHODS: Pressure overload was imposed on mice by transverse aortic constriction and the vascular structure of the heart was examined using a tissue transparency technique. Functional and molecular analyses including single-cell RNA sequencing were performed on the hearts of wild-type mice and EC-specific gene knockout mice. Metabolites in heart tissue were measured by capillary electrophoresis-time of flight-mass spectrometry system. The vaccine was prepared by conjugating the synthesized epitope peptides with keyhole limpet hemocyanin and administered to mice with aluminum hydroxide as an adjuvant. Tissue samples from heart failure patients were used for single-nucleus RNA sequencing to examine gene expression in ECs and perform pathway analysis in cardiomyocytes. RESULTS: Pressure overload induced the development of intricately entwined blood vessels in murine hearts, leading to the accumulation of replication stress and DNA damage in cardiac ECs. Inhibition of cell proliferation by a cyclin-dependent kinase inhibitor reduced DNA damage in ECs and ameliorated transverse aortic constriction-induced cardiac dysfunction. Single-cell RNA sequencing analysis revealed upregulation of Igfbp7 (insulin-like growth factor-binding protein 7) expression in the senescent ECs and downregulation of insulin signaling and oxidative phosphorylation in cardiomyocytes of murine and human failing hearts. Overexpression of Igfbp7 in the murine heart using AAV9 (adeno-associated virus serotype 9) exacerbated cardiac dysfunction, while EC-specific deletion of Igfbp7 and the vaccine targeting Igfbp7 ameliorated cardiac dysfunction with increased oxidative phosphorylation in cardiomyocytes under pressure overload. CONCLUSIONS: Igfbp7 produced by senescent ECs causes cardiac dysfunction and vaccine therapy targeting Igfbp7 may be useful to prevent the development of heart failure. [ABSTRACT FROM AUTHOR]

Background: Bursectomy, the total resection of the bursa omentalis, is a standard procedure in gastrectomy for resectable gastric cancer. A phase III trial (JCOG1001) comparing bursectomy and omentectomy alone was terminated early at the interim analysis. The final results of the updated analysis after a minimum follow-up of 5 years are reported here. Background: Bursectomy, the total resection of the bursa omentalis, is a standard procedure in gastrectomy for resectable gastric cancer. A phase III trial (JCOG1001) comparing bursectomy and omentectomy alone was terminated early at the interim analysis. The final results of the updated analysis after a minimum follow-up of 5 years are reported here. Results: A total of 1204 patients (602 bursectomy and 602 omentectomy alone) were enrolled between June 2010 and March 2015. The bursectomy group had a significantly higher incidence of Clavien-Dindo grade III-IV intra-abdominal abscess than the omentectomy-alone group (5.5 versus 2.5 per cent respectively; P= 0.008). The updated 5-year overall survival rates were 74.9 (95 per cent c.i. 71.2 to 78.2) per cent in the bursectomy group and 76.5 (72.8 to 79.7) per cent in the omentectomy-alone group; the adjusted HR for death in the bursectomy group was 1.03 (95 per cent c.i. 0.83 to 1.27) (1-sided P=0.598). Bursectomy did not decrease peritoneal recurrence (12.1 versus 12.3 per cent respectively; P= 1.000). In a multivariable analysis, old age (above 65 years), tumour located in the lower third or posterior wall of the stomach, macroscopic type 3/5, total gastrectomy, and cT4a were independent predictors of poor overall survival, but omentectomy alone was not. Conclusion: In D2 gastrectomy, bursectomy is not recommended as a standard procedure for cT3-T4a gastric cancer. Registration number: UMIN000003688 (https://www.umin.ac.jp/ctr/). [ABSTRACT FROM AUTHOR]

BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) for gastric cancer may prevent the loss of body weight and lean body mass resulting from reduced surgical stress in comparison to open distal gastrectomy (ODG). A multicenter phase III trial conducted by the Japan Clinical Oncology Group (JCOG0912 trial) was performed to confirm the non-inferiority of LADG to ODG for stage I gastric cancer in terms of relapse-free survival. METHODS: This study was performed as a single-institution exploratory analysis using the data of the patients from our hospital who were enrolled in the JCOG0912 phase III trial. Body weight and lean body mass were evaluated using a bioelectrical impedance analyzer within 1 week before and at 1 week, 1 month, and 3 months after surgery. RESULTS: One-hundred six patients were randomized to undergo ODG (54 patients) or LADG (51 patients). Body weight loss at 1 week, 1 month, and 3 months was -3.0%, -4.9%, and -5.4%, respectively, in the ODG group and -2.7%, -4.3%, and -5.7%, respectively, in the LADG group; the differences were not statistically significant (p = 0.330, 0.166, and 0.656, respectively). Lean body mass loss at 1 week, 1 month, and 3 months was -2.8%, -4.1%, and -2.3%, respectively, in the ODG group and -2.7%, -2.9%, and -3.0%, respectively, in the LADG group; the differences were not statistically significant (p = 0.610, 0.413, and 0.925, respectively). CONCLUSIONS: The laparoscopic approach did not attenuate the loss of body weight and lean body mass in comparison to patients who underwent open distal gastrectomy for gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Serum C-reactive protein (CRP) level can be an indicator of the early stage of infectious complications. However, its utility in advanced esophageal cancer patients who receive radical esophagectomy with two- or three-field lymph node dissection with perioperative steroid therapy and enhanced recovery after surgery (ERAS) care is unclear.Methods: The present study retrospectively examined 117 consecutive esophageal cancer patients who received neoadjuvant chemotherapy followed by radical esophagectomy. All patients received perioperative steroid therapy and ERAS care. The utility of the CRP value in the early detection of serious infectious complications (SICs) was evaluated based on the area under the receiver operating characteristic curve (AUC). Univariate and multivariate logistic regression analyses were performed to identify the risk factors for SICs.Results: SICs were observed in 20 patients (17.1%). The CRP level on postoperative day (POD) 4 had superior diagnostic accuracy for SICs (AUC 0.778). The cut-off value for CRP was determined to be 4.0 mg/dl. A multivariate analysis identified CRP ≥ 4.0 mg/dl on POD 4 (odds ratio, 18.600; 95% confidence interval [CI], 4.610-75.200) and three-field lymph node dissection (odds ratio, 7.950; 95% CI, 1.900-33.400) as independent predictive factors.Conclusions: CRP value on POD 4 may be useful for predicting SICs in esophageal cancer patients who receive radical esophagectomy with perioperative steroid therapy and ERAS care. This result may encourage the performance of imaging studies to detect the focus and thereby lead to the early medical and/or surgical intervention to improve short-term outcomes. [ABSTRACT FROM AUTHOR]

The insulin-like growth factors (IGF) system is involved in tumor proliferation, invasion and metastasis in cancer. The current study investigated the association of IGF-1, IGF-2 and IGF-1 receptor (IGF-1R), IGF binding proteins type 3 (IGFBP-3) mRNA expression levels with clinicopathological characteristics and outcomes of 202 patients with untreated colorectal cancer (CRC). IGF-1, IGF-2, IGF-1R and IGFBP-3 mRNA expression levels were analyzed in surgical specimens of cancer tissues and adjacent normal mucosa cells using reverse transcription-quantitative polymerase chain reaction. The IGF-1R gene expression level was significantly higher in cancer tissue compared with adjacent normal mucosa. By contrast, IGF-1 gene expression levels were reduced in cancer tissue compared with normal mucosa. IGF-2 and IGFBP-3 gene expression levels did not differ significantly between cancer tissue and adjacent normal mucosa. As for the association of gene expression and clinicopathological characteristics, IGFBP-3 gene expression was significantly associated with lymph node metastasis. High IGFBP-3 gene expression was associated with poor 5-year overall survival compared with patients with low IGFBP-3 expression. Furthermore, IGFBP-3 gene expression was identified as an independent prognostic factor using multivariate analysis. Overexpression of the IGFBP-3 gene is considered an effective independent predictor of outcomes in patients with CRC. [ABSTRACT FROM AUTHOR]