The cardiovascular safety of denosumab has not yet been evaluated in a systematic review. This systematic review and meta‐analysis sought to quantify the number of randomized controlled trials (RCTs) of denosumab (against comparators) reporting cardiovascular adverse events (CAEs) and examine the balance of CAEs between treatment arms. MEDLINE, Embase, and http://clinicaltrials.gov were searched from inception to October 26, 2019, for RCTs of denosumab versus comparators for any indication. Included trials were randomized, enrolled ≥100 participants, and reported bone‐related outcomes. Primary outcome for analysis was all CAEs, a composite endpoint representing summation of all CAEs as reported by included trials. Secondary outcomes included major adverse cardiovascular events (MACE). Data were pooled using a fixed effects model to determine relative risk (RR) and 95% confidence interval (95% CI). Risk of bias was assessed using the Cochrane risk‐of‐bias tool. Of 554 records screened, 49 were included, while 36 reported CAEs. Twenty‐seven included trials (12 eligible for meta‐analysis) were conducted in 13,202 postmenopausal women. Compared with bisphosphonates, there was a 46% (95% CI 1.05 to 2.02) increase in CAEs (85/2136 events in denosumab‐treated versus 58/2131 events in bisphosphonate‐treated; seven trials). There was a similar imbalance in a five‐point (stroke, myocardial infarction, cardiovascular death, heart failure, atrial fibrillation) MACE endpoint (28/2053 versus 12/2050; RR = 2.33 [1.19 to 4.56]). Compared with placebo‐treated women, there was no imbalance in total CAEs (439/4725 events in denosumab versus 399/4467 in placebo; RR = 0.79 [0.41 to 1.52]; seven trials). No imbalance in total AEs (versus bisphosphonates: 0.98 [0.92 to 1.04]; versus placebo: 0.99 [0.98 to 1.01]) occurred. Other indications showed no statistically significant results. The excess CAEs in postmenopausal women treated with denosumab compared with bisphosphonates, but not placebo, indirectly supports claims that bisphosphonates may suppress CAEs. Future trials should use standardized CAE reporting to better describe cardiovascular effects of bone active medications. (PROSPERO: CRD42019135414.) © 2020 American Society for Bone and Mineral Research (ASBMR).

No abstract

Background Emergency colorectal surgery tends to be associated with poorer outcomes compared to elective colorectal surgery. This study assessed the morbidity and mortality in patients undergoing emergency and elective colorectal resection in two metropolitan hospitals. Methods Patients were identified retrospectively from two institutions between April 2018 and July 2020. Baseline, operative and postoperative parameters were collected for comparative analysis between emergency and elective surgery groups. A binary logistic regression was performed to identify independent predictors of postoperative complications. Results During the study period, 454 patients underwent colorectal resection, 135 were emergency cases (29.74%) and 319 were elective cases (70.26%). Compared with elective resections, patients undergoing emergency resections were observed to have a higher American Society of Anesthesiologists (ASA) score of III to IV (53.33% vs. 38.56%) (P = 0.004). The mortality rate was similar between the emergency and elective group (1.48% vs. 0.63%, P = 0.369). The overall complication rate was higher in patients undergoing emergency resections (64.44% vs. 36.68%, P < 0.001), but the major complication rate was similar between groups (12.59% vs. 10.34%, P = 0.484). Independent predictors for postoperative complications included emergency surgery (Odds Ratio (OR) 2.77, 95% Confidence Interval (CI): 1.66 to 4.61) and an ASA Score of III to IV (OR 2.87, 95% CI: 1.84 to 4.47). Conclusion The overall complication rate was higher in patients undergoing emergency colorectal resection, however, rates of major complications and mortality were similar between groups. Higher complication rates reflect advanced disease pathology in patients who are more comorbid.

No abstract