3D QSAR study on substituted 1, 2, 4 triazole derivatives as anticancer agents by kNN MFA approach.

Background and objectives: Researchers have recently focused on the biological and synthetic effects of 1, 2, and 4-triazole fused heterocyclic molecules because they have tremendous medicinal value. The objective of the present study was to carry out the 3D QSAR evaluation on the substituted 1,2, and 4 triazole derivatives for anticancer potential using k-Nearest Neighbor-Molecular Field Analysis (kNN-MFA) method. Methods: Using the molecular design suite, a three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was undertaken on a series of 4-amino-5-(pyridin3yl)-4H-1, 2, and 4-triazole-3-thiol anticancer drugs (Vlife MDS). This study used a genetic algorithm and a manual selection approach on 20 substituted 1, 2, and 4-triazole derivatives. Based on the genetic algorithm (GA), the 3D-QSAR model was generated. Statistical significance and predictive capacity were evaluated using internal and external validation. Results: The most significant model has a correlation coefficient of 0.9334 (squared correlation coefficient r2 = 0.8713), showing that biological activity and descriptors have a strong relationship. The model exhibited internal predictivity of 74.45 percent (q2 = 0.2129), external predictivity of 81.09 percent (pred r2 = 0.8417), and the smallest error term for the predictive correlation coefficient (pred r2se = 0.1255). The model revealed steric (S 1047--0.0780--0.0451S 927) and electrostatic (E 1002) data points that contribute remarkably to anticancer activity. A molecular field study demonstrates a link between the structural features of substituted triazole derivatives and their activities. Conclusion: The good-to-moderate anticancer potential of compounds confirms the significant pharmacological role of 1,2,4-triazole derivatives. These results could lead to the identification of potential chemical compounds with optimal anticancer activity and minimal side effects.

Polypharmacy in chronic liver disease patients: Implications for disease severity, drug-drug interaction, and quality of life.

Multiple prescriptions for different medications may be needed for chronic conditions, increasing the risk of polypharmacy. The WHO defined polypharmacy as "the administration of many drugs at the same time or the administration of an excessive number of drugs". The primary goal of this study was to evaluate polypharmacy in patients with chronic liver disease and to identify potential drug-drug interactions associated with it. A cross-sectional study was conducted at a tertiary care hospital in Mangalore, Karnataka, for six months, from November 2020 to April 2021. The study involved 118 patients with chronic liver disease from various age groups. Data was gathered by analyzing patients' medical records kept on the ward and interviewing them individually. In admission and discharge prescriptions, polypharmacy was examined. Online interaction checkers from Drugs.com and Medscape were used to interpret potential drug-drug interactions. The SF-36 and Chronic Liver Disease Questionnaire were used to measure the quality of life. The data obtained were analyzed statistically to determine the significant correlation. The number of prescribed drugs was significantly correlated (P = 0.018) with the severity of liver disease in Child-Pugh categories B and C. Additionally, moderate polypharmacy reduced quality of life (P < 0.05), and the physical health category was significantly associated with disease severity (P < 0.05). Drug-drug interactions were found in 108 out of the 118 examined prescriptions, totaling 586 interactions in the admission list and 405 interactions in the discharge list. If the potentially serious main drug interaction identified in this study is not well monitored, it could lead to a serious, potentially fatal health condition. Despite being advised, safety is not always guaranteed by liver enzyme monitoring. Therefore, healthcare providers must take additional precautions to avoid inappropriate prescribing, minimize side effects, and ensure drug safety.

Endoscopic revision of gastric bypass: Holy Grail or Epic fail?

BACKGROUND: Approximately 20-30 % of patients who undergo Roux-en-Y gastric bypass (RYGB) will not meet the goals of weight loss surgery. Revisional surgery is associated with higher morbidity compared to initial operative management, and results in terms of weight loss have been inconsistent. Endoscopic plication has been seen as a less invasive option, with encouraging initial results. The objective was to analyze the outcomes after Restorative Obesity Surgery, Endolumenal (ROSE) procedure. METHODS: We retrospectively analyzed patients who underwent ROSE between 5/2008 and 11/2013. All patients had failure of weight loss or regain weight after RYGB. Demographics, operative data, and follow-up were recorded. RESULTS: Twenty-seven patients underwent ROSE. One patient was excluded due to lack of follow-up. Twenty-five (96 %) patients were female. Mean time since initial RYGB was 11.9 ± 4.3 years. Mean initial weight and BMI were 236 ± 47 lb and 40.6 ± 8.1 kg/m(2), respectively. Mean OR time was 77 ± 30 min. Preoperative average pouch length and stoma diameter were 6.8 ± 2.3 and 2.1 ± 0.7 cm, respectively. On average, 4 ± 1.6 stitches were placed. Final pouch length and stoma diameter were 3.4 ± 1.6 (50 % reduction) and 0.86 ± 0.4 cm (61 % reduction). A total of 12 (46 %) and seven (28 %) patients underwent EGD at 3 and 12 months postoperatively. The mean pouch length and stoma diameter were 5 ± 1.9 (26.5 % reduction) and 1.2 ± 0.7 cm (42.9 % reduction) at 3 months and 6.14 ± 1.6 (10 % reduction) and 2.2 ± 1.2 cm (4.7 % increase) at 12 months, respectively. The %EWL was 8.9, 9.3, 8, 6.7, -10.7, -13.5, -5.8, -4.5 at 3, 6, 12, 24, 36, 48, 60, and 72 months, respectively. CONCLUSION: Although endoscopic plication achieved the intended reduction in the pouch and stoma diameter at 3 months, these tend toward the preoperative diameter at 12 months. This anatomical failure and the lack of follow-up may explain why most patients failed to achieve sustainable weight loss.

Foramen of Winslow hernia: a minimally invasive approach.

Hernias through the foramen of Winslow comprise 8 % of all internal hernias and the majority contain incarcerated bowel. Clinical signs are often non-specific and delay in diagnosis associated with a mortality rate that approaches 50 %. Management is urgent surgical reduction with bowel decompression and resection of devitalized bowel. A foramen of Winslow hernia (FWH) has traditionally been managed via an exploratory laparotomy incision and the vast majority of cases describe an open approach. We describe a minimally invasive approach to the management of an incarcerated FWH requiring decompression and bowel resection.

Laparoscopic cholecystectomy using a novel single-incision surgical platform through a standard 15 mm trocar: initial experience and technical details.

OBJECTIVE: Single-incision minimally invasive surgery has previously been associated with incisions 2.0-3.0 cm in length. We present a novel single-incision surgical platform compatible for insertion through a standard 15-mm trocar. The objective of this study is to evaluate the safety and feasibility of the platform. METHODS: The technology is currently a Phase I investigational device. It features articulating surgical instruments and is inserted through a multiple-use introducer. The platform's introducer requires a standard 15-mm laparoscopic trocar. Cholecystectomy is performed through a 15-mm umbilical incision utilizing an additional epigastric 2-mm needle-port grasper for gallbladder retraction. A prospective feasibility study was performed at a single-center. Inclusion criteria were age 18-75 years and biliary colic. Patients were excluded if they had acute cholecystitis, dilation of the biliary tree, severe coagulopathy, BMI > 40 kg/m(2), or choledocholithiasis. Endpoints included the success rate of the platform, hospital length of stay, post-operative pain medication usage, cosmetic results, and presence of hernia. RESULTS: Six patients (5 female) with an average age of 41 years and BMI 28 kg/m(2) underwent cholecystectomy with the platform. Average OR time was 91 min and umbilical incision length did not exceed 15 mm. One case was converted to standard laparoscopy due to mechanical failure of the clip applier instrument. There were no intraoperative complications. Post-operatively, two patients developed self-resolving umbilical ecchymoses. Average length of stay was 13 h. Pain control was achieved with diclofenac for less than 7 days. At 1 month follow-up there were no complications and no umbilical hernias. CONCLUSIONS: This phase I study demonstrates that single-incision cholecystectomy through a 15-mm trocar with the Fortimedix Surgical B.V. single-incision surgical platform is feasible, safe, and reproducible. Additional benefits include excellent triangulation and range of motion as well as exceptional cosmetic results. Further studies will be needed to evaluate long-term hernia rates.