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IntroductionThe increasing prevalence of obesity has led to an increase in total knee arthroplasties (TKAs) being undertaken in patients with a higher body mass index (BMI). TKA in morbidly obese patients can be technically challenging due to numerous anatomical factors and patient co-morbidities. The long-term outcomes in this patient group are unclear. This systematic review aims to compare the long-term revision rates, functional outcomes and complication rates of TKAs in morbidly obese versus non-obese patients.MethodsA search of PubMed, EMBASE and PubMed Central was conducted to identify studies that reported revision rates in a cohort of morbidly obese patients (BMI ≥ 40 kg/m2) that underwent primary TKA, compared to non-obese patients (BMI ≤ 30 kg/m2). Secondary outcomes included Knee Society Objective Scores (KSOS), Knee Society Functional Scores (KSFS), and complication rates between the two groups. The difference in revision rates was assessed using the Chi-squared test. The Wilcoxon signed-rank test was used to compare pre-operative and post-operative functional scores for each group. KSOS and KSFS for morbidly obese and non-obese patients were compared using the Mann–Whitney test. Statistical significance was defined as p ≤ 0.05.ResultsNine studies were included in this review. There were 624 TKAs in morbidly obese patients and 9,449 TKAs in non-obese patients, average BMI values were 45.0 kg/m2 (range 40–66 kg/m2) and 26.5 kg/m2 (range 11–30 kg/m2) respectively. The average follow-up time was 4.8 years (range 0.5–14.1) and 5.2 years (range 0.5–13.2) respectively, with a revision rate of 7% and 2% (p < 0.001) respectively. All functional scores improved after TKA (p < 0.001). Pre- and post-operative KSOS and KSFS were poorer in morbidly obese patients, however, mean improvement in KSOS was the same in both groups and comparable between groups for KSFS (p = 0.78). Overall complication rates,  including infection, were higher in morbidly obese patients.ConclusionsThis review suggests an increased mid to long-term revision rate following primary TKA in morbidly obese patients, however, these patients have a functional recovery which is comparable to non-obese individuals. There is also an increased risk of perioperative complications, such as superficial wound infection. Morbidly obese patients should be fully informed of these issues prior to undergoing primary TKA.

Increased reactive oxygen species (ROS) contribute to asthma, but little is known about the molecular mechanisms connecting increased ROS with characteristic features of asthma. We show that enhanced oxidative activation of the Ca2+/calmodulin-dependent protein kinase (ox-CaMKII) in bronchial epithelium positively correlates with asthma severity and that epithelial ox-CaMKII increases in response to inhaled allergens in patients. We used mouse models of allergic airway disease induced by ovalbumin (OVA) or Aspergillus fumigatus (Asp) and found that bronchial epithelial ox-CaMKII was required to increase a ROS- and picrotoxin-sensitive Cl− current (ICl) and MUC5AC expression, upstream events in asthma progression. Allergen challenge increased epithelial ROS by activating NADPH oxidases. Mice lacking functional NADPH oxidases due to knockout of p47 and mice with epithelial-targeted transgenic expression of a CaMKII inhibitory peptide or wild-type mice treated with inhaled KN-93, an experimental small molecule CaMKII antagonist, were protected against increases in ICl, MUC5AC expression, and airway hyper-reactivity to inhaled methacholine. Our findings support the view that CaMKII is a ROS-responsive, pluripotent pro-asthmatic signal and provide proof-of-concept evidence that CaMKII is a therapeutic target in asthma.