Intra-operative Tranexamic Acid Administration Significantly Decreases Incidence of Postoperative Bleeding Without Increasing Venous Thromboembolism Risk After Laparoscopic Sleeve Gastrectomy: a Retrospective Cohort Study of Over 400 Patients.

BACKGROUND: There is evidence that tranexamic acid (TXA) reduces surgical bleeding and is widely used in trauma, obstetrics and other specialties. This practice is less well-established in laparoscopic sleeve gastrectomy (LSG) due to concerns surrounding venous thromboembolism (VTE); equally postoperative bleeding is a serious complication often requiring re-operation. METHODS: This retrospective cohort study compared 30-day outcomes following primary LSG in patients receiving intra-operative TXA (March 2020-July 2022) to those who did not (March 2011-March 2020). The primary outcome was postoperative bleeding (Hb < 9 g/dL) requiring transfusion or re-operation. Secondary outcomes were incidence of VTE, serious postoperative complications (Clavien-Dindo > grade 3) and death. Patients underwent standardised-protocol LSG without staple line re-enforcement under a single surgeon within the independent sector (private practice). TXA 1 g intravenous was administered immediately after a methylene blue leak test, prior to extubation. RESULTS: TXA group had 226 patients and non-TXA group had 192 patients. Mean age was 40.5 ± 10.3 and 39.1 ± 9.8 years, respectively. In the TXA group, no postoperative bleeds [versus 3 (1.6%) in non-TXA group, p = 0.0279] occurred. One staple line leak (0.4%) occurred in the TXA group compared to zero in the non-TXA group (p = ns). There was no VTE or death. CONCLUSIONS: This is the largest cohort study of intra-operative TXA in primary LSG to date, which demonstrates significant decrease in postoperative bleeding without increasing VTE risk. The authors recommend administration of TXA immediately following leak test, or removal of bougie to maximise efficacy. Data of TXA in LSG is awaited from the randomised controlled PATAS trial.

Effect of indomethacin on embryo implantation and histomorphology of uterus, ovary, kidney, and liver of rats.

Background: This study aimed to determine the effects of Indomethacin (IMC) treatment on embryo implantation and histomorphology of uterus, ovary, and other vital organs and its effective dosage in establishing embryo implantation dysfunction model in Sprague-Dawley (SD) rats. Materials and Methods: The experiments were performed on 24 (6 × 4 groups) adult female SD rats aged 12 weeks old. G1 was the control group and received a normal diet with normal saline. However, on pregnancy days 3 (Pd3) and 4 (Pd4), G2, G3, and G4 were given normal saline and subcutaneously administered IMC twice daily at different doses of 4.33, 4.66 and 5.00 mg/kg body weight, respectively. The rats were euthanized on day 8 of pregnancy (Pd8). The uterus was excised and examined for signs of pregnancy, followed by tissue samples from liver, kidney, and ovary (for histomorphological examination using haematoxylin and eosin stain). Results: All IMC treatment doses disrupted the implantation process and caused a significant reduction in embryo development. Analysis for histopathological changes revealed that IMC doses above 4.33 mg/kg body weight caused more adverse reproductive health effects in rats. Vasoconstriction and micro vascularization were detected in the liver, while degenerative Bowman's capsules and inflammatory cells were observed in kidney sections from IMC-treated rats. Conclusion: IMC therapy interfered with implantation and embryo development in rats, resulting in significant uterine vasoconstriction and atrophy, 4.33 mg/kg bwt dose appeared to be optimum to establish embryo implantation dysfunction in SD rats.

Impact of Cadmium and Lead Exposure on Camel Testicular Function: Environmental Contamination and Reproductive Health.

The free grazing habits of camels from various sources may cause heavy metals to bioaccumulate in their tissues and organs, possibly resulting in higher amounts of these toxic substances in their bodies over time. The aim of this study was to assess the exposure impact of lead (Pb) and cadmium (Cd) on bull camels of the Lassi breed, aged 7 to 8 years, at a site near the industrial area and another two non-industrial sites, to analyze the presence of heavy metals. Samples from three sites were collected from thirty camels (n = 10/each), soil and water (n = 30), and five different plants (n = 15/each) for analysis. Testes were collected for atomic absorption spectrometry (AAS), and hematoxylin-eosin (HE) staining. Serum samples were obtained to measure testosterone levels by radioimmunoassay (RIA). Samples were obtained from plants, soil, water, blood, serum and urine for AAS. According to the results, the testes' weight, length, width, and volume significantly decreased at the industrial site compared with the other two sites as a result of exposure to Cd and Pb. Additionally, blood testosterone concentrations were considerably lower at the industrial site, indicating a detrimental impact on testicular steroidogenesis. The histological investigation of the industrial site indicated structural disturbances, including seminiferous tubule degeneration and shedding, cellular debris in seminiferous tubules, lining epithelium depletion, and vacuolation. Elevated amounts of Cd and Pb were found at the industrial site when analyzed using water, soil, plants, testes, serum, and urine. These findings demonstrate the adverse effects of Pb and Cd exposure on camel testicular function, including decreased weight and altered steroidogenesis. These findings are essential for understanding the impact of exposure to Pb and Cd on camel reproductive function and for developing successful prevention and management plans for these exposures in this species.

Discovery and Optimization of Potent and Orally Available CTP Synthetase Inhibitors for Use in Treatment of Diseases Driven by Aberrant Immune Cell Proliferation.

Herein, we report the discovery of a first-in-class chemotype 2-(alkylsulfonamido)thiazol-4-yl)acetamides that act as pan-selective inhibitors of cytidine 5'-triphosphate synthetase (CTPS1/2), critical enzymes in the de novo pyrimidine synthesis pathway. Weak inhibitors identified from a high-throughput screening of 240K compounds have been optimized to a potent, orally active agent, compound 27, which has shown significant pharmacological responses at 10 mg/kg dose BID in a well-established animal model of inflammation.

Edible bird's nest protects histomorphology of rat's uterus against cadmium (Cd) toxicity through a reduction of Cd deposition and enhanced antioxidant activity.

Cadmium (Cd) is often associated with reproductive disorders of mammals. Edible bird's nest (EBN) is a natural food product made of swiftlet's salivary secretion used to make their nests and it has been consumed as a tonic food for decades. This research aimed to study the protective effects of EBN against Cd-induced uterine toxicity in Sprague Dawley rats. Thirty (30) female Sprague Dawley rats were assigned into five groups as follows: group 1- negative control (NC) received distilled water; group 2 - positive control (PC) administered with CdCl2, 5 mg/kg BW; while groups EBN-1, EBN-2, and EBN-3 received CdCl2 (5 mg/kg BW) plus graded concentrations of 60, 90 and 120 mg/kg BW of EBN, respectively. After four weeks of daily oral treatment, rats were euthanized to collect the uterus for evluations of histopathological changes, Cd concentrations and Metallothionein (MT) expressions using H&E stain, inductive coupled plasma mass spectrometry (ICP-MS) and immunohistochemistry, respectively. Blood samples were collected for superoxide dismutase (SOD) analysis using SOD assay kit. Results revealed that the CdCl2 without EBN supplement (PC) group had elevated levels of Cd in the uterus along with increased MT expressions and decreased SOD enzyme activity as compared to the NC group. Moreover, uterine histopathological changes, including glandular cysts and loss of normal structure of luminal epithelium (LE) and glandular epithelium (GE) were found in the PC group. Interestingly, groups treated with CdCl2 along with EBN (EBN1, EBN2, EBN3) showed lower levels of uterine tissue Cd deposition and MT expression, lower degenerative changes with normal histomorphology of glands, and increased SOD activity as compared to the PC group. Overall, the findings revealed that oral exposure to Cd at a dose of 5 mg/kg BW resulted in significant alterations in the rat's uterus. However, the toxicity effect was averted by EBN treatment in a dose dependant manner; highest protection achieved with EBN 120 mg/kg BW, through a possible detoxification mechanism and prevention of Cd deposition.

Expedient synthesis of an atypical oxazolidinone compound library.

In order to address the current downturn in the drug discovery pipeline, initiatives are being undertaken to synthesise screening libraries of sp3-rich, low molecular weight compounds. As part of the European Lead Factory initiative, the synthesis and derivatisation of a simple hexahydrooxazolo[5,4-c]pyridin-2(1H)-one bicyclic carbamate has been achieved. The synthetic route employed involved a telescoped hetero-Diels-Alder/[2,3]-sigmatropic rearrangement/cyclisation sequence to deliver the desired core scaffold containing two points for further diversification. When applied, this synthesis was found to be robust and scalable which allowed the production of a 155 compound library.

Predictive power of Mannheim Peritonitis Index.

OBJECTIVE: To evaluate Mannheim Peritonitis Index (MPI) in predicting outcome in patients with secondary peritonitis and to assess each risk factor independently regarding its contribution towards final outcome. DESIGN: Prospective analytical study. PLACE AND DURATION OF STUDY: Surgical Unit-II of Rawalpindi General Hospital, from December 1999 to January 2001. PATIENTS AND METHODS: One hundred and twenty-six patients who presented to the department with secondary peritonitis were included in the study. MPI score was calculated for each patient on a pre-designed proforma and the patients were followed-up till death or discharged from the hospital. Death was the main outcome measure against which the MPI scores were analyzed under two categories; (i) score > or = 26 and < 26 (ii) scores < 21, 2-29, and > 29. Data was analyzed on software SPSS (version 11.0). Chi-square test was used to assess any significant association between scores and outcome. Odds ratios were calculated for individual risk factors. RESULTS: Mortality rate for MPI score > or = 26 was 28.1% while for scores less than 26 it was 4.3%. For MPI scores pound 20 mortality rate was 1.9%, for scores 21-29 it was 21.9% and for score 30 or more it was 28.1%. Chi-square showed significant association between mortality and increasing MPI score (p < 0.01). Odd ratios calculated were significant for age > 50 years, malignancy, organ failure, pre-operative duration of peritonitis > 24 hours and cloudy, purulent exudate. CONCLUSION: Increasing MPI score is strongly associated with outcome in secondary peritonitis.