Does body mass index influence improvement in patient reported outcomes following total knee arthroplasty? A retrospective analysis of 3918 cases

Abstract Purpose The study aimed to determine whether body mass index (BMI) classification for patients undergoing total knee arthroplasty (TKA) is associated with differences in mean patient reported outcome measure (PROM) score improvements across multiple domains—including pain, functional status, mental health, and global physical health. We hypothesized that patients with larger BMIs would have worse preoperative and postoperative PROM scores, though improvements in scores would be comparable between groups. Materials and methods Patients undergoing primary TKA from 2018 to 2021 were retrospectively reviewed and stratified into four groups: Normal Weight; 18.5–25 kg/m2, Overweight; 25.01–30 kg/m2, Obese; 30.01–40 kg/m2, and Morbidly Obese > 40 kg/m2. Preoperative, postoperative, and pre/post-changes (Δ) in knee injury and osteoarthritis, joint replacement (KOOS, JR) and Patient-Reported Outcome Measurement Information System (PROMIS) measures of pain intensity, pain interference, physical function, mobility, mental health, and physical health were compared. Multivariate linear regression was used to assess for confounding comorbid conditions. Results In univariate analysis, patients with larger BMIs had worse scores for KOOS, JR and all PROMIS metrics preoperatively. Postoperatively, scores for KOOS, JR and PROMIS pain interference, mobility, and physical health were statistically worse in higher BMI groups, though differences were not clinically significant. Morbidly obese patients achieved greater pre/post-Δ improvements in KOOS, JR and global physical health scores. Multivariate regression analysis showed high BMI was independently associated with greater pre/post-Δ improvements in KOOS, JR and global health scores. Conclusion Obese patients report worse preoperative scores for function and health, but greater pre/post-Δ improvements in KOOS, JR and physical health scores following TKA. Quality of life benefits of TKA in obese patients should be a factor when assessing surgical candidacy

Changes in Ultra-Processed Food Consumption and Lifestyle Behaviors Following COVID-19 Shelter-in-Place: A Retrospective Study

Ultra-processed food (UPF) consumption poses a potential risk to public health and may be related to shelter-in-place orders. This study utilized the level of food processing as a lens by which to examine the relationships between diet, weight change, and lifestyle changes (including cooking, snacking, and sedentary activity) that occurred during regional shelter-in-place orders. This study used a cross-sectional, retrospective survey (n = 589) to assess baseline demographics, changes in lifestyle behaviors using a Likert scale, and changes in dietary behaviors using a modified food frequency questionnaire from mid-March to May 2020; data were collected in the California Bay Area from August to October 2020. Foods were categorized by level of processing (minimally processed, processed, and ultra-processed) using the NOVA scale. Stepwise multiple linear regression and univariate linear regression models were used to determine the associations between these factors. Increased snacking was positively associated with a change in the percent of the calories derived from UPF and weight gain (β = 1.0, p < 0.001; β = 0.8 kg, p < 0.001) and negatively associated with the share of MPF calories consumed (β = -0.9, p < 0.001). These relationships have public health implications as interventions designed around decreased snacking may positively impact diet and weight management and thereby mitigate negative health outcomes

A CRISPR/Cas9-engineered ARID1A-deficient human gastric cancer organoid model reveals essential and non-essential modes of oncogenic transformation.

Mutations in ARID1A rank amongst the most common molecular aberrations in human cancer. However, oncogenic consequences of ARID1A mutation in human cells remain poorly defined due to lack of forward genetic models. Here, CRISPR/Cas9-mediated ARID1A knockout in primary TP53-/- human gastric organoids induced morphologic dysplasia, tumorigenicity and mucinous differentiation. Genetic Wnt/B-catenin activation rescued mucinous differentiation, but not hyperproliferation, suggesting alternative pathways of ARID1A KO-mediated transformation. ARID1A mutation induced transcriptional regulatory modules characteristic of MSI and EBV subtype human gastric cancer, including FOXM1-associated mitotic genes and BIRC5/survivin. Convergently, high-throughput compound screening indicated selective vulnerability of ARID1A-deficient organoids to inhibition of BIRC5/survivin, functionally implicating this pathway as an essential mediator of ARID1A KO-dependent early-stage gastric tumorigenesis. Overall, we define distinct pathways downstream of oncogenic ARID1A mutation, with non-essential Wnt-inhibited mucinous differentiation in parallel with essential transcriptional FOXM1/BIRC5-stimulated proliferation, illustrating the general utility of organoid-based forward genetic cancer analysis in human cells