Alpha‐1‐antitrypsin in cell and organ transplantation

Limited availability of donor organs and risk of ischemia‐reperfusion injury (IRI) seriously restrict organ transplantation. Therapeutics that can prevent or reduce IRI could potentially increase the number of transplants by increasing use of borderline organs and decreasing discards. Alpha‐1 antitrypsin (AAT) is an acute phase reactant and serine protease inhibitor that limits inflammatory tissue damage. Purified plasma–derived AAT has been well tolerated in more than 30 years of use to prevent emphysema in AAT‐deficient individuals. Accumulating evidence suggests that AAT has additional anti‐inflammatory and tissue‐protective effects including improving mitochondrial membrane stability, inhibiting apoptosis, inhibiting nuclear factor kappa B activation, modulating pro‐ vs anti‐inflammatory cytokine balance, and promoting immunologic tolerance. Cell culture and animal studies have shown that AAT limits tissue injury and promotes cell and tissue survival. AAT can promote tolerance in animal models by downregulating early inflammation and favoring induction and stabilization of regulatory T cells. The diverse intracellular and immune‐modulatory effects of AAT and its well‐established tolerability in patients suggest that it might be useful in transplantation. Clinical trials, planned and/or in progress, should help determine whether the promise of the animal and cellular studies will be fulfilled by improving outcomes in human organ transplantation.     

Working Memory Training for Adolescents With Cannabis Use Disorders: A Randomized Controlled Trial

Adolescent cannabis use is associated with working memory impairment. The present randomized controlled trial assigned adolescents ages 14 to 21 enrolled in cannabis use treatment to receive either working memory training (experimental group) or a control training (control group) as an adjunctive treatment. Cognitive function, drug use, and other outcomes were assessed before and after training. We observed few differences in cognitive, functional, or self-reported drug use outcomes as a function of training group, although tetrahydrocannabinol (THC) urinalysis results favored the experimental group. These findings are similar to previous studies in substance users, which have shown limited transfer effects for working memory training.     

Severe Obesity Increases Risk of Infection After Revision Total Hip Arthroplasty

BackgroundThe increasing prevalence of obesity has resulted in an increased number of revision total hip arthroplasties (rTHAs) performed in patients with a high body mass index (BMI). The aim of this study is to evaluate whether obesity negatively affects (1) complication rate, (2) reoperation and revision rate, and (3) patient-reported outcome in rTHA.MethodsIn this registry-based study, we prospectively followed 444 rTHAs (cup: n = 265, stem: n = 57, both: n = 122) performed in a specialized high-volume orthopedic center between 2013 and 2015. The number of complications, and reoperation and revision surgery was registered until 5 years postoperatively. Oxford Hip Score (OHS) was evaluated preoperatively, and at 1 and 2 years postoperatively. Patients were categorized based on BMI to nonobese (<30 kg/m², n = 328), obese (30-35 kg/m², n = 82), and severe obese (≥35 kg/m², n = 34).ResultsSevere obese patients, but not obese patients, had higher risks of complications and re-revision than nonobese patients. In particular, the risk of infection following rTHA was higher in severe obese patients (24%) compared to nonobese patients (3%; relative risk, 7.7). Severe obese patients had overall poorer OHS than nonobese patients, but improvement in OHS did not differ between severe obese and nonobese patients. No differences between obese and nonobese groups on OHS were observed.ConclusionIn our study, severe obesity was associated with an increased risk of infection following rTHA. Patients with high BMI should be counseled appropriately before surgery.