Bayesian parametric estimation based on left-truncated competing risks data under bivariate Clayton copula models.

In observational/field studies, competing risks and left-truncation may co-exist, yielding 'left-truncated competing risks' settings. Under the assumption of independent competing risks, parametric estimation methods were developed for left-truncated competing risks data. However, competing risks may be dependent in real applications. In this paper, we propose a Bayesian estimator for both independent competing risks and copula-based dependent competing risks models under left-truncation. The simulations show that the Bayesian estimator for the copula-based dependent risks model yields the desired performance when competing risks are dependent. We also comprehensively explore the choice of the prior distributions (Gamma, Inverse-Gamma, Uniform, half Normal and half Cauchy) and hyperparameters via simulations. Finally, two real datasets are analyzed to demonstrate the proposed estimators.

The integration of the intracorporeal triangular anastomotic technique in robotic distal gastrectomy: advancing patient safety and procedural simplicity.

BACKGROUND: Robotic distal gastrectomy (RDG) with Billroth I (BI) reconstruction is predominantly performed due to its physiological congruence and simplicity. The Intracorporeal Triangular Anastomotic Technique (INTACT) aims to reduce ischemic areas compared to the conventional Delta-shaped anastomosis using the unique characteristics of robotic surgery to standardize procedures, thereby ensuring safe, simple, and reliable reconstruction. This study aims to investigate the efficacy of the INTACT in RDG with BI reconstruction, focusing on its robotic precision in minimizing ischemic zones and improving surgical reliability. SURGICAL TECHNIQUE: The posterior duodenal wall is dissected before reconstruction, and the hepatoduodenal ligament is severed to facilitate passive duodenal manipulation. A quarter-circumference incision is created centrally on the anterior wall of the duodenal stump to avoid excessive tension during anastomosis and to ensure an adequate anastomotic diameter. A small opening is established on the greater curvature of the remaining stomach, and the posterior walls of the stomach and duodenum are joined using a Linear stapler in the first fire. A V-shape is created, and two EndoWrist instruments (robotic first and fourth arms) are utilized to grip and extend the anastomosis diameter, completing the anastomosis with a shared hole closure using the Linear stapler. The robotic arms' features improve the physiological integrity and stability of the BI reconstruction. RESULTS: A total of 81 patients underwent RDG with INTACT from September 2020 to January 2024. The median age was 72 years (range: 31-91), with 49 males and 32 females. The median blood loss was 0 ml (range: 0-200 ml), and the median postoperative hospital stay was 8 days (range: 6-20 days). No cases required reanastomosis during surgery, and no postoperative anastomotic leakage, surgery-related reoperations, or anastomotic strictures were reported. CONCLUSION: INTACT in RDG can be safely performed. The characteristics of the EndoWrist instruments helped in stabilizing the technique, making it a viable option in robotic-assisted surgeries.

A case of hepatoid adenocarcinoma of the lung harboring KRAS G12C responded favorably to sotorasib.

Hepatoid adenocarcinoma of the lung is a rare variant of adenocarcinoma. We describe a case of hepatoid adenocarcinoma of the lung that harbored KRAS G12C and responded favorably to sotorasib. A man in his 70s was found to have an abnormality on his chest X-ray. He underwent right middle lobectomy, and a pathological examination of the surgical specimen showed conventional invasive adenocarcinoma with highly focal hepatoid adenocarcinoma. He received chemoradiotherapy and concurrent radiation, followed by durvalumab for postoperative recurrence. After three doses of durvalumab, he reported feeling short of breath. A computed tomography scan showed emerging broad consolidation in the right lower lobe. Transbronchial lung biopsy specimens from the consolidation showed hepatoid adenocarcinoma harboring KRAS G12C mutation. Therefore, he was started on sotorasib 960 mg daily. Eight days later, a computed tomography scan showed that the area of consolidation had reduced in size. Progressive disease was detected after 42 days of treatment with sotorasib. The patient died 1 month after cessation of sotorasib and 3 months after postoperative recurrence. We have encountered what we believe to be the first case of hepatoid adenocarcinoma of the lung with KRAS G12C mutation that responded favorably to treatment with sotorasib.

Anti-Inflammatory, Wound Healing, and Anti-Diabetic Effects of Pure Active Compounds Present in the Ryudai Gold Variety of Curcuma longa.

Turmeric (Curcuma longa) contains curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). Nevertheless, curcumin is the most researched active ingredient for its numerous pharmacological effects. We investigated the impact of these curcuminoids found in Ryudai gold, an approved cultivar of Curcuma longa, on wound healing, inflammation, and diabetes. Sub-planter injections of carrageenan induced acute paw inflammation in rats. The wound-healing ability of 1% curcuminoids was examined by making a 6 mm round wound on the shaved dorsum of the mice with a biopsy punch. A single intraperitoneal injection of streptozotocin (50 mg/kg) was used to induce diabetes in mice. Curcuminoids at a dose rate of 100 mg/kg body weight were used with feed and as a gastric gavage to treat diabetes and inflammation in experimental animals. Paw thickness was measured at 1, 3, and 6 h following carrageenan injection. After three hours, mean paw volume was 58% in carrageenan-injected mice, which was 35%, 37%, and 31% in the curcumin, DMC, and BDMC groups, respectively. Histopathology of the paw tissue demonstrated severe infiltration of inflammatory cells and thickening of the dermis, which were remarkably improved by the curcuminoids. The wound-healing abilities were significantly higher in the curcumin- (95.0%), DMC- (93.17%), and BDMC-treated (89.0%) groups, in comparison to that of the control (65.09%) group at day nine. There were no significant differences in wound-healing activity among the groups treated with 1% curcuminoids throughout the study. Streptozotocin-induced diabetes was characterized by an increased blood glucose (552.2 mg/dL) and decreased body weight (31.2 g), compared to that of the control rats (145.6 mg/dL and 46.8 g blood glucose and body weight, respectively). It also caused an increase in serum alanine aminotransferase (ALT; 44.2 U/L) and aspartate aminotransferase (AST; 55.8 U/L) compared to that of the control group (18.6 U/L and 20.1 U/L, respectively). Histopathological examination of the liver showed that diabetes caused hepatic cellular necrosis, congestion of the central vein, and parenchymatous degeneration. However, all three curcuminoids significantly decreased blood glucose levels, ALT, and AST and improved the histopathological score of the liver. These results evidenced that not only curcumin but also DMC and BDMC have potent anti-inflammatory, wound healing, and anti-diabetic efficacy, and the Ryudai gold variety of turmeric could be used as a functional food supplement.

Combination of transbronchoscopic oxygen insufflation and a digital chest drainage system in endobronchial occlusion: a hybrid technique for localization of fistula in intractable pneumothorax.

BACKGROUND: The management of intractable secondary pneumothorax poses a considerable challenge as it is often not indicated for surgery owing to the presence of underlying disease and poor general condition. While endobronchial occlusion has been employed as a non-surgical treatment for intractable secondary pneumothorax, its effectiveness is limited by the difficulty of locating the bronchus leading to the fistula using conventional techniques. This report details a case treated with endobronchial occlusion where the combined use of transbronchoscopic oxygen insufflation and a digital chest drainage system enabled location of the bronchus responsible for a prolonged air leak, leading to the successful treatment of intractable secondary pneumothorax. CASE PRESENTATION: An 83-year-old male, previously diagnosed with chronic hypersensitivity pneumonitis and treated with long-term oxygen therapy and oral corticosteroid, was admitted due to a pneumothorax emergency. Owing to a prolonged air leak after thoracic drainage, the patient was deemed at risk of developing an intractable secondary pneumothorax. Due to his poor respiratory condition, endobronchial occlusion with silicone spigots was performed instead of surgery. The location of the bronchus leading to the fistula was unclear on CT imaging. When the bronchoscope was wedged into each subsegmental bronchus and low-flow oxygen was insufflated, a digital chest drainage system detected a significant increase of the air leak only in B5a and B5b, thus identifying the specific location of the bronchus leading to the fistula. With the occlusion of those bronchi using silicone spigots, the air leakage decreased from 200 mL/min to 20 mL/min, and the addition of an autologous blood patch enabled successful removal of the drainage tube. CONCLUSION: The combination of transbronchoscopic oxygen insufflation with a digital chest drainage system can enhance the therapeutic efficacy of endobronchial occlusion by addressing the problems encountered in conventional techniques, where the ability to identify the leaking bronchus is dependent on factors such as the amount of escaping air and the location of the fistula.

Acute exacerbation predicting poor outcomes in idiopathic interstitial pneumonia and advanced lung cancer patients undergoing cytotoxic chemotherapy.

Effective treatment for advanced lung cancer and idiopathic interstitial pneumonia (IIP) remains an unmet medical need. The relationship between chemotherapy's effectiveness in advanced lung cancer and the risk of acute exacerbation of IIP is poorly investigated. There is limited evidence that patients who experience an acute exacerbation of IIPs during cytotoxic chemotherapy have poorer outcomes than those who do not. Among 1004 patients with advanced lung cancer and IIPs enrolled in our published multi-centre retrospective study from 110 Japanese institutions, 708 patients (male: female, 645:63; mean age, 70.4) received first-line chemotherapy. The occurrence of chemotherapy-triggered acute exacerbations of IIPs and overall survival (OS) were analysed. The OS between groups of patients with and without the occurrence of acute exacerbation was compared at four landmark time points (30, 60, 90, and 120 days), starting from the first-line chemotherapy, using the landmark method. The incidence of acute exacerbation in patients who received first-line chemotherapy with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) was more frequent in NSCLC patients than in SCLC (4.2% vs 12.6%; odds ratio [OR]: 3.316; 95% confidence interval [CI] 1.25-8.8). Median survival time was 9.9 months (95% CI 9.2-10.7). Patients who experienced acute exacerbation had significant worse survival outcomes than those who did not at various time points (30 days, hazard ratio [HR]: 5.191, 95% CI 2.889-9.328; 60 days, HR: 2.351, 95% CI 1.104-5.009; 90 days, HR: 2.416, 95% CI 1.232-4.739; and 120 days, HR: 2.521, 95% CI 1.357-4.681). Acute exacerbation during first-line chemotherapy can predict poor survival.Trial Registration number: UMIN000018227.

Enhancing surgical outcomes in elderly gastric cancer patients: the role of comprehensive preoperative assessment and support.

BACKGROUND: As the prevalence of gastric cancer rises in aging populations, managing surgical risks and comorbidities in elderly patients presents a unique challenge. The Comprehensive Preoperative Assessment and Support (CPAS) program, through comprehensive preoperative assessments, aims to mitigate surgical stress and improve outcomes by enhancing patient awareness and preparation. This study investigates the efficacy of a CPAS program, incorporating frailty and sarcopenia evaluations, to improve short-term outcomes in elderly gastric cancer patients. METHODS: A retrospective analysis was conducted on 127 patients aged 75 or older who underwent surgery with CPAS between 2018 and August 2023, compared to 170 historical controls from 2012 to 2017. Propensity score matching balanced both groups based on age-adjusted Charlson Comorbidity Index and surgical details. The primary focus was on the impact of CPAS elements such as rehabilitation, nutrition, psychological support, oral frailty, and social support on short-term surgical outcomes. RESULTS: Among 83 matched pairs, the CPAS group, despite 40.4% of patients in the CPAS group and 21.2% in the control group had an ASA-PS score of 3 or higher (P < 0.001), demonstrated significantly reduced blood loss (100 ml vs. 190 ml, P = 0.026) and lower incidence of serious complications (19.3% vs. 33.7%, P = 0.034), especially in infections and respiratory issues. Sarcopenia was identified in 38.6% of CPAS patients who received tailored support. Additionally, the median postoperative hospital stay was notably shorter in the CPAS group (10 days vs. 15 days, P < 0.001), with no in-hospital deaths. These results suggest that personalized preoperative care effectively mitigates operative stress and postoperative complications. CONCLUSION: Implementing CPAS significantly enhances surgical safety and reduces complication rates in elderly gastric cancer patients, emphasizing the critical role of personalized preoperative care in surgical oncology for this demographic.

Effects of Maturation on Antibacterial Properties of Vietnamese Mango (Mangifera indica) Leaves.

This study, for the first time, has investigated the relationships between alterations of mangiferin contents in mango leaves at different maturity stages and their antibacterial properties. Leaves were classified into six different maturity stages based on their color: (1) young dark reddish brown, (2) young yellow, (3) young light green, (4) mature green, (5) old dark green, and (6) old yellow leaves. Ethanol extracts were then examined against Gram-positive and Gram-negative bacteria, applying broth dilution and agar well diffusion methods. In addition, we also measured the mangiferin contents in leaves at different stages for the purpose of evaluating how the changes in this phytochemistry value affects their activities against bacteria. The results showed that extracts from leaves at young ages had better antibacterial properties than those from old leaves, as evidenced by the lower minimum inhibitory concentrations and larger inhibitory zones. In addition, we also found that the contents of mangiferin were significantly decreased followed the maturation process. These results suggest that mango leaves at young stages, especially dark reddish brown and young yellow leaves, are preferable for application in bacterial infections and other therapies related to mangiferin's constituents.

Early detection of occupational cholangiocarcinoma in a high-risk patient under intensive surveillance: a case study.

BACKGROUND: Occupational cholangiocarcinoma is associated with exposure to organic solvents, such as dichloromethane (DCM) and 1,2-dichloropropane (DCP). This report describes a case of occupational cholangiocarcinoma detected through regularly imaging following the discovery of elevated serum γ-glutamyl trans peptidase (γ-GTP) levels revealed during regular checkup. CASE PRESENTATION: A 43-year-old man who had been working in a printing company with 15 years of exposure to organic solvents presented to our hospital owing to abnormalities found during a routine checkup. Ultrasound (US) imaging revealed thickening of the gallbladder wall accompanied by gallstones, although in the blood tests, γ-GTP levels were within normal range. Given the high risk of cholangiocarcinoma development, the patient underwent regular monitoring with abdominal US and blood tests at a local doctor's office. At the age of 48, his serum γ-GTP level mildly elevated for the first time, prompting the initiation of semi-annual magnetic resonance cholangiopancreatography (MRCP). By the age of 50 years, dilation in B8 was detected, and one and a half years later, a tumor on the central side of the B8 dilation appeared. The patient was diagnosed with intrahepatic cholangiocarcinoma, which was treated with anterior sectionectomy. Pathological examination revealed an adenocarcinoma with a papillary glandular ductal structure at the root of the B8. In addition, biliary intraepithelial neoplasia (BilIN) and dysplasia have been identified around the tumor and periphery bile ducts and in noncancerous bile ducts. Postoperatively, the patient received 6 months of adjuvant chemotherapy with S-1monotherapy. Eight months after surgery, the patient remained under observation with no signs of recurrence. CONCLUSIONS: We report a case of occupational cholangiocarcinoma detected during a prolonged period of regular follow-up after exposure to DCM and DCP. Given the delayed carcinogenesis process, occupational cholangiocarcinomas manifest long after exposure to organic solvents, therefore, ongoing screening is extremely important. Vigilance is essential to avoid underdiagnosis, particularly for individuals who are at an increased risk of developing this form of cancer. Continuous monitoring is key to the early detection and effective management of occupational cholangiocarcinoma.

Japanese guidelines for the treatment of idiopathic pulmonary fibrosis 2023:Revised edition.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with a poor prognosis and an unknown cause that generally progresses to pulmonary fibrosis and leads to irreversible tissue alteration. The "Guidelines for the treatment of idiopathic pulmonary fibrosis 2017," specializing in the treatment of IPF for the first time in Japan and presenting evidence-based standard treatment methods suited to the state of affairs in Japan, was published in 2017, in line with the 2014 version of "Formulation procedure for Minds Clinical Practice Guidelines." Because new evidence had accumulated, we formulated the "Guidelines for the treatment of Idiopathic Pulmonary Fibrosis 2023 (revised 2nd edition)." While keeping the revision consistent with the ATS/ERS/JRS/ALAT IPF treatment guidelines, new clinical questions (CQs) on pulmonary hypertension were added to the chronic stage, in addition to acute exacerbation and comorbid lung cancer, which greatly affect the prognosis but are not described in the ATS/ERS/JRS/ALAT IPF guidelines. Regarding the advanced stages, we additionally created expert consensus-based advice for palliative care and lung transplantation. The number of CQs increased from 17 in the first edition to 24. It is important that these guidelines be used not only by respiratory specialists but also by general practitioners, patients, and their families; therefore, we plan to revise them appropriately in line with ever-advancing medical progress.