1,3,5-Thiadiazinane thione derivatives as significant urease inhibitors.

We report the promising urease inhibitory activity of four sets of tetrahydro thiadiazine thiones (THTT) namely 3,5-disubstituted tetrahydro-2H-1,3,5-thiadiazine thiones: THTT 5-8 (set A) having alkyl/aryl substituents at N-3 and N-5 positions; THTT 9-12 (set B) and THTT 13-14 (set C) with 3-carboxylic acid derivatives and tetrahydro-2H-1,3,5-thiadiazine-6-thione esters 15-16 (set D). Gratifyingly, all four sets of THTT were recognized as promising inhibitors of urease enzyme. Among 12 tested compounds; THTT 6, 8, 10, 14 and 15 from each set respectively, demonstrated significant urease inhibitory activity with IC50 values between 11.2-29.8µM which is mostly found higher than that for thiourea, a standard urease inhibitor with IC50 value of 22.4µM. Furthermore, compound 7 showed almost the same level of inhibition (IC50 = 22.5µM) as of standard. In addition, molecular docking study supported the phenomenon that thiadiazinane ring itself is an active pharmacophore that binds through CH2 groups and S atom via carbon-hydrogen/π-sulfur interactions respectively to the active site of the urease enzyme. The optimistic results from this study suggest the use of thiadiazinane skeleton as a guided template for the advancement of new urease inhibitors in drug discovery.

Bronchoscopic retrieval of an aspirated tooth following high-speed motor vehicle accident.

A 28-year-old man aspirated a tooth into his right lower lobe bronchus following a high-speed motor vehicle accident. Initial retrieval attempts failed with a flexible bronchoscope, but a cryoprobe successfully dislodged and retrieved the tooth. Cryoprobe should be considered for bronchoscopic foreign body removal when conventional methods are unsuccessful.

Lymphomatoid granulomatosis mimicking PJP infection.

A male patient in his 40s who had been unwell for months with fever of unknown origin and clinicopathological features suspicious for haemophagocytic lymphohistiocytosis presented to hospital with worsening subacute shortness of breath. CT pulmonary angiogram demonstrated ground glass changes involving all lung lobes with an apicobasal gradient. These changes, combined with long-term steroid exposure for granulomatous hepatitis without pneumocystis prophylaxis, raised concern for pneumocystis jirovecii pneumonia (PJP). A subsequent bronchoscopic lavage specimen was positive on PCR for PJP and the patient was started on appropriate therapy. Clinical and radiological changes initially improved but after completion of therapy, symptoms and radiological abnormalities returned. Retreatment with second-line treatment resulted again in initial improvement followed by relapse with acute deterioration. Further investigations for an alternate diagnosis were made, with a surgical lung biopsy performed finally revealing immunosuppression-related Epstein-Barr virus positive large B cell lymphoma with lymphomatoid granulomatosis of grade 3 pattern.

A rare case of isolated ACTH deficiency associated with a Rathke's Cleft Cyst and a review of the literature.

A 78-year-old man was referred to clinic due to a 5-year history of weight loss, lethargy, and pathology showing hyponatremia. In the year prior, he had a hospital admission for symptomatic hyponatremia. MRI brain during that admission showed a 1-2 mm pituitary lesion of unknown significance. Testing during this presentation revealed hypocortisolism with ACTH deficiency. Progress MRI brain revealed the presence of a Rathke's Cleft Cyst (RC). Medical management with glucocorticoids resulted in symptomatic and biochemical parameter improvement. To our knowledge this is the first reported case of isolated ACTH deficiency in the setting of a RC.

Does a stoma reduce the risk of anastomotic leak and need for re-operation following low anterior resection for rectal cancer: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: There is a relatively high risk of anastomotic leak in low anterior resection (LAR), associated with significant morbidity and mortality. This systematic review and meta-analysis aims to compare diverting stoma vs. no stoma for LAR in terms of leak rates, reoperations, mortality rates and complication rates. METHODS: We systematically performed electronic searches of databases Ovid Medline, PubMed, CCTR, CDSR, ACP Journal Club and DARE from inception to present. Only randomized controlled trials comparing LAR for rectal cancer with versus without stoma diversion were included for analysis. Main outcomes were anastomotic leak, reoperation rate and mortality. Secondary outcomes included other operative and stoma-related complications. RESULTS: Eight randomized controlled trials were included in the study for qualitative and quantitative analyses. A significantly longer operative duration for patients with stoma diversion was seen (WMD 19.50 min; 95% CI: 7.38, 31.63; I2=0%, P=0.002). The pooled rate for anastomotic leak was significantly lower for those with stoma diversion (6.3% vs. 18.3%; RR 0.36; 95% CI: 0.24, 0.54; I2=0%; P<0.00001). There was lower reoperation rate for patients with stoma diversion compared to no stoma (5.9% vs. 16.7%; RR 0.40; 95% CI: 0.26, 0.60; I2=0%; P<0.00001). No significant difference was found in terms of leak-related mortality between stoma vs. no-stoma cohorts (0.47% vs. 1.0%; P=0.51). CONCLUSIONS: The present meta-analysis suggests a diverting or defunctioning stoma following LAR for rectal cancers can reduce anastomotic leak and reoperation rates, without increased risk of mortality or other complications.

Alcohol use disorders before and after bariatric surgery: a systematic review and meta-analysis.

BACKGROUND: There have been increasing reports of increased risk of alcohol use disorder (AUD) in the post bariatric surgery patient. The aim of this systematic review and meta-analysis is to observe the rate of AUD in the postoperative period following bariatric surgery for weight management. METHODS: Electronic searches were performed using six databases from their dates of inception to January 2017. Studies observing the trend in AUD post bariatric surgery were identified. Data for relevant endpoint was extracted and analysed. RESULTS: Ten studies were identified for inclusion of analyses. One year post operatively pooled odds were 1.004 [95% confidence interval (CI), 0.921-1.094; P=0.935], with no significant difference found in the proportion of patients with AUD at 1 year vs. pre-surgery. Two years post operatively pooled odds were 0.981 (95% CI, 0.843-1.142; P=0.806), with no significant difference found in the proportion of patients with AUD at 2 years vs. pre-surgery. Three years post operatively pooled odds were 1.825 (95% CI, 1.53-2.178; P<0.001) with a significant increase in AUD particularly with gastric bypass surgery. CONCLUSIONS: In conclusion, prevalence of AUD increases in patients undergoing gastric bypass surgery but not gastric banding. The risk of AUD was found to not be significantly increased in the first 2 years postoperatively but increasing after this period.