In-vitro and in-vivo evaluation of the anticancer activity of diruthenium-2, a new trithiolato arene ruthenium complex [(η6-p-MeC6H4Pri)2Ru2(µ-S-p-C6H4OH)3]Cl.

In the present study, we investigated the anticancer action of the trithiolato arene ruthenium complex, [(η-p-MeC6H4Pr)2Ru2(µ-S-p-C6H4OH)3]Cl, named diruthenium-2, both in vitro and in vivo. The mechanism of antiproliferative, cytotoxic, and DNA-damaging activity, and the effect on expressions of cell cycle regulatory proteins were investigated using a WST-1-based proliferation assay, lactate dehydrogenase leakage assay, comet assay, flow cytometry, and western blot analysis. In-vivo anticancer activity was evaluated using Ehrlich tumor-bearing NMRI mice. Diruthenium-2 inhibited the growth of all cancer cell lines used, the most sensitive being gastric (AGS), breast cancer (BT-549, MCF-7, MDA-MB-231), and leukemic (HL-60, MOLT-4) cells. In MCF-7 cells, it caused a G1/S cell cycle arrest, along with an increase in the expression of protein p21 and cyclin B1. We also observed increased levels of MRN complex proteins, which, together with the results from the comet assay, indicate the formation of DNA double-strand breaks. In tumor-bearing mice, diruthenium-2 at doses of 3 and 5 mg/kg inhibits the growth of solid Ehrlich tumor, although weaker than cisplatin. However, it did not prolong the post-therapeutic survival. Our results suggest the in-vitro potential of diruthenium-2 should be further evaluated in studies using other in-vivo models.

Development and Validation of a Mobile Clinical Decision Support Tool for the Diagnosis of Drug Allergy in Adults: The Drug Allergy App.

BACKGROUND: Penicillin allergy overdiagnosis has been associated with inappropriate antibiotic prescribing, increased antimicrobial resistance, worse clinical outcomes, and increased health care costs. OBJECTIVE: To develop and validate a questionnaire-based algorithm built in a mobile application to support clinicians in collecting accurate history of previous reactions and diagnosing drug allergy appropriately. METHODS: A survey was completed by 164 medical and nonmedical prescribers to understand barriers to best practice. Based on the survey recommendations, we created a 10-item questionnaire-based algorithm to allow classification of drug allergy history in line with the National Institute for Health and Care Excellence guidelines on drug allergy. The algorithm was incorporated into a mobile application and retrospectively validated using anonymized clinical databases at regional immunology and dermatology centers in Manchester, United Kingdom. RESULTS: A total of 55.2% of prescribers (95% confidence interval, 47% to 63.4%) thought it impossible to draw a firm conclusion based on history alone and 59.4% (95% CI, 51.4% to 67.5%) believed that regardless of the details of the penicillin allergy history, they would avoid all ß-lactams. A drug allergy mobile application was developed and retrospectively validated, which revealed a low risk for misclassification of outcomes compared with reference standard drug allergy investigations in the allergy and dermatology clinics. CONCLUSIONS: Perceived lack of time and preparedness to collect an accurate drug allergy history appear to be important barriers to appropriate antimicrobial prescribing. The Drug Allergy App may represent a useful clinical decision support tool to diagnose drug allergy correctly and support appropriate antibiotic prescribing.

Elbow instability following lateral collateral ligament complex avulsion fracture and joint interposition: an uncommon presentation.

The lateral collateral ligament (LCL) complex of the elbow is a capsuloligamentous structure, critical for elbow stability. Though isolated ligamentous injuries have been reported in literature, there are no studies reporting avulsion fractures of the lateral ligamentous complex of the elbow with joint incarceration in a child. An 11-year-old boy presented to the emergency department after a fall from height, with pain and swelling to the lateral side of his left elbow. Radiographs established a fracture of the lateral condyle and CT imaging confirmed an avulsion of the lateral ligamentous complex, with fragments in the inferior radiocapitellar joint. Examination under anaesthesia revealed an unstable elbow with restricted extension, and the child underwent joint debridement and open reduction internal fixation of LCL complex with cannulated screws. At the final follow-up at 15 months, the child regained preinjury level of function.