Prior surgical fixation of proximal humerus fractures is associated with increased complications following subsequent reverse shoulder arthroplasty

BackgroundThe objective of this study was to compare complication rates between patients undergoing reverse shoulder arthroplasty (RSA) after a prior open reduction and internal fixation (ORIF) for proximal humerus fracture (PHF) to those undergoing RSA as a primary treatment for PHFs, glenohumeral osteoarthritis, or rotator cuff tear arthropathy (CTA).MethodsPatients who underwent RSA between 2015 and 2020 were identified in the Mariner database. Patients were separated into 3 mutually exclusive groups: (1) RSA for osteoarthritis, rotator cuff tear, or CTA (Control-RSA); (2) RSA as a primary treatment for PHF (PHF-RSA); and (3) RSA for patients with prior ORIF of PHFs (ORIF-RSA). Ninety-day medical and 2-year postoperative surgical complications were identified. In addition, patients in the PHF-RSA group were subdivided into those undergoing RSA for PHF within 3 months of the fracture (acute) vs. those treated greater than 3 months from diagnosis (delayed). Multivariate regression was performed to control for differences in comorbidities and demographics.ResultsA total of 30,824 patients underwent primary RSA for arthritis or CTA, 5389 patients underwent RSA as a primary treatment for a PHF, and 361 patients underwent RSA after ORIF of a PHF. ORIF before RSA was associated with an increased risk of overall revision (odds ratio [OR] 2.45, P = .002), infection (OR 2.40, P < .001), instability (OR 2.43, P < .001), fracture (OR 3.24, P = .001), minor medical complications (OR 1.59, P = .008), and readmission (OR 2.55, P = .001) compared with the Control-RSA cohort. RSA as a primary treatment for PHF was associated with an increased risk of 2-year revision (OR 1.60, P < .001), infection (OR 1.51, P < .001), instability (OR 2.84, P < .001), and fracture (OR 2.54, P < .001) in addition to major medical complications (OR 2.02, P < .001), minor medical complications (OR 1.92, P < .001), 90-day emergency department visits (OR 1.26, P < .001) and 90-day readmission (OR 2.03, P < .001) compared with the Control-RSA cohort. The ORIF-RSA group had an increased risk of periprosthetic infection (OR 1.94, P = .002) when compared with the PHF-RSA cohort. There were no differences in medical or surgical complications in the RSA-PHF cohort between patients treated in an acute or delayed fashion.ConclusionRSA following ORIF of a PHF is associated with increased complications compared with patients undergoing RSA for nonfracture indications. Prior ORIF of a PHF is also an independent risk factor for postoperative infection after RSA compared with patients who undergo RSA as a primary operation for fracture. The timing of RSA as a primary operation for PHF does not appear to impact the rates of postoperative medical and surgical complications.     

Losing the uphill battle? Emergent harm reduction interventions and barriers during the opioid overdose crisis in Canada

Canada continues to experience an escalating opioid overdose crisis that has claimed more than 8000 lives in the country since 2016. The presence of the synthetic opioid fentanyl and its analogues is a central contributor to the increases in preventable opioid-related deaths. However, a number of converging social-structural factors (e.g., the continued criminalisation of drug use, political changes) and political barriers are also complicating and contributing to the current crisis. We briefly outline four harm reduction interventions (i.e., injectable opioid agonist treatment, naloxone distribution programs, overdose prevention sites, and drug checking services) as emerging and rapidly expanding responses to this crisis in Canada. These examples of innovation and expansion are encouraging but also occurring at the same time that the opioid overdose crisis shows few signs of abating. To truly address the crisis, Canada needs political environments at all government levels that are responsive and foster harm reduction innovation and drug policy experimentation.     

Development of an IgG-Fc fusion COVID-19 subunit vaccine,AKS-452

AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.     

Tissue tracking of segmental strain as a predictor of provoked dynamic left ventricular outflow tract obstruction

BackgroundLeft ventricular outflow tract obstruction (LVOTO) is commonly observed in patients with hypertrophic cardiomyopathy (HCM) or left ventricular hypertrophy (LVH). Some patients develop LVOTO provoked by physical exertion, and hence termed dynamic LVOTO (DLVOTO). However, its precise prevalence and mechanism are still unclear.AimTwo-dimensional speckle tracking echocardiography (2D STE) seems to be helpful for the detection of early LV structural abnormalities. This study aimed to examine the possible role of segmental as well as global longitudinal strain in identifying DLVOTO non-HCM patients as detected by dobutamine stress echocardiography (DSE).Methods and resultsTwo hundred and fifty patients without structural heart disease had undergone conventional transthoracic echocardiography, 2D STE, and DSE. All patients with non-ischemic evidence were divided into two groups according to the DSE results; DLVOTO (+) and DLVOTO (?).Among 250 patients, 50 patients (36%) had shown DLVOTO after DSE (15 males, 35 females; mean age 55±7years). They were compared with 90 non -LVOTO obstruction patients (43 males, 47 females; mean age 57±6years). Based on multivariate logistic regression analysis, the independent predictors of provoked DLVOTO during DSE were resting basal septal longitudinal strain BS-LS _average (p < 0.001), resting LA reservoir strain (p < 0.001), and systolic LVOT diameter (p = 0.03). Resting BS-LS _average with cut-off - 17.5% was recognized as a critical indicator of DLVOTO, with sensitivity 78%, and specificity 95% (better than systolic LVOT diameter of sensitivity 76%, and specificity 15% and resting LA reservoir strain which showed poor AUC at ROC curve 0.007).ConclusionWe demonstrate that provoked LVOTO during DSE in non HCM symptomatic patients is directly correlated to resting regional LS, where the increased BS-LS of ≥ ?17.5% was a key determinant of LVOT gradient provocation. Assessment of baseline BS-LS _average might be a bedside simple tool for detection of patients with DLVOTO not able to do DSE.