Citations

Background: Studies evaluating the natural history of femoroacetabular impingement (FAI) are limited. Purpose: To stratify the risk of progression to osteoarthritis (OA) in patients with FAI using an unsupervised machine-learning algorithm, compare the characteristics of each subgroup, and validate the reproducibility of staging. Study Design: Cohort study (prognosis); Level of evidence, 2. Methods: A geographic database from the Rochester Epidemiology Project was used to identify patients with hip pain between 2000 and 2016. Medical charts were reviewed to obtain characteristic information, physical examination findings, and imaging details. The patient data were randomly split into 2 mutually exclusive sets: train set (70%) for model development and test set (30%) for validation. The data were transformed via Uniform Manifold Approximation and Projection and were clustered using Hierarchical Density-based Spatial Clustering of Applications with Noise. Results: The study included 1071 patients with a mean follow-up period of 24.7 ± 12.5 years. The patients were clustered into 5 subgroups based on train set results: patients in cluster 1 were in their early 20s (20.9 ± 9.6 years), female dominant (84%), with low body mass index (<19 ); patients in cluster 2 were in their early 20s (22.9 ± 6.7 years), female dominant (95%), and pincer-type FAI (100%) dominant; patients in cluster 3 were in their mid 20s (26.4 ± 9.7) and were mixed-type FAI dominant (92%); patients in cluster 4 were in their early 30s (32.7 ± 7.8), with high body mass index (≥29 ), and diabetes (17%); and patients in cluster 5 were in their early 30s (30.0 ± 9.1), with a higher percentage of males (43%) compared with the other clusters and with limited internal rotation (14%). Mean survival for clusters 1 to 5 was 17.9 ± 0.6, 18.7 ± 0.3, 17.1 ± 0.4, 15.0 ± 0.5, and 15.6 ± 0.5 years, respectively, in the train set. The survival difference was significant between clusters 1 and 4 ( P = .02), 2 and 4 ( P < .005), 2 and 5 ( P = .01), and 3 and 4 ( P < .005) in the train set and between clusters 2 and 5 ( P = .03) and 3 and 4 ( P = .01) in the test set. Cluster characteristics and prognosis was well reproduced in the test set. Conclusion: Using the clustering algorithm, it was possible to determine the prognosis for OA progression in patients with FAI in the presence of conflicting risk factors acting in combination.

Background Remote limb ischemic postconditioning (RLIPoC) has been demonstrated to protect against ischemic stroke. However, the underlying mechanisms of RLIPoC mediating cross‐organ protection remain to be fully elucidated. Methods and Results Ischemic stroke was induced by middle cerebral artery occlusion for 60 minutes. RLIPoC was performed with 3 cycles of 10‐minute ischemia followed by 10‐minute reperfusion of the bilateral femoral arteries immediately after middle cerebral artery reperfusion. The percentage of regulatory T cells (Tregs) in the spleen, blood, and brain was detected using flow cytometry, and the number of Tregs in the ischemic hemisphere was counted using transgenic mice with an enhanced green fluorescent protein‐tagged Foxp3. Furthermore, the metabolic status was monitored dynamically using a multispectral optical imaging system. The Tregs were conditionally depleted in the depletion of Treg transgenic mice after the injection of the diphtheria toxin. The inflammatory response and neuronal apoptosis were investigated using immunofluorescent staining. Infarct volume and neurological deficits were evaluated using magnetic resonance imaging and the modified neurological severity score, respectively. The results showed that RLIPoC substantially reduced infarct volume, improved neurological function, and significantly increased Tregs in the spleen, blood, and ischemic hemisphere after middle cerebral artery occlusion. RLIPoC was followed by subsequent alteration in metabolites, such as flavin adenine dinucleotide and nicotinamide adenine dinucleotide hydrate, both in RLIPoC‐conducted local tissues and circulating blood. Furthermore, nicotinamide adenine dinucleotide hydrate can mimic RLIPoC in increasing Tregs. Conversely, the depletion of Tregs using depletion of Treg mice compromised the neuroprotective effects conferred by RLIPoC. Conclusions RLIPoC protects against ischemic brain injury, at least in part by activating and maintaining the Tregs through the nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide hydrate pathway.

Background: Meniscal allograft transplant (MAT) is an important treatment option for young patients with deficient menisci; however, there is a lack of consensus on the optimal method of allograft fixation. Hypothesis: The various methods of MAT fixation have measurable and significant differences in outcomes. Study Design: Meta-analysis; Level of evidence, 4. Methods: A single-arm meta-analysis of studies reporting graft failure, reoperations, and other clinical outcomes after MAT was performed. Studies were stratified by suture-only, bone plug, and bone bridge fixation methods. Proportionate rates of failure and reoperation for each fixation technique were pooled with a mixed-effects model, after which reconstruction of relative risks with confidence intervals was performed using the Katz logarithmic method. Results: A total of 2604 patients underwent MAT. Weighted mean follow-up was 4.3 years (95% CI, 3.2-5.6 years). During this follow-up period, graft failure rates were 6.2% (95% CI, 3.2%-11.6%) for bone plug fixation, 6.9% (95% CI, 4.5%-10.3%) for suture-only fixation, and 9.3% (95% CI, 6.2%-13.9%) for bone bridge fixation. Transplanted menisci secured using bone plugs displayed a lower risk of failure compared with menisci secured via bone bridges (RR = 0.97; 95% CI, 0.94-0.99; P = .02). Risks of failure were not significantly different when comparing suture fixation to bone bridge (RR = 1.02; 95% CI, 0.99-1.06; P = .12) and bone plugs (RR = 0.99; 95% CI, 0.96-1.02; P = .64). Allografts secured using bone plugs were at a lower risk of requiring reoperations compared with those secured using sutures (RR = 0.91; 95% CI, 0.87-0.95; P < .001), whereas allografts secured using bone bridges had a higher risk of reoperation when compared with those secured using either sutures (RR = 1.28; 95% CI, 1.19-1.38; P < .001) or bone plugs (RR = 1.41; 95% CI, 1.32-1.51; P < .001). Improvements in Lysholm and International Knee Documentation Committee scores were comparable among the different groups. Conclusion: This meta-analysis demonstrates that bone plug fixation of transplanted meniscal allografts carries a lower risk of failure than the bone bridge method and has a lower risk of requiring subsequent operations than both suture-only and bone bridge methods of fixation. This suggests that the technique used in the fixation of a transplanted meniscal allograft is an important factor in the clinical outcomes of patients receiving MATs.

A rare APOE variant APOE3 -Jac reduces self-aggregation and promotes healthy brain aging.

AbstractBackground and ObjectivesThe prognostic significance of regression in predicting melanoma recurrences is unknown. We present a large multicenter study correlating regression with recurrence.MethodsThe Sentinel Lymph Node Working Group database was queried from 1993 to 2018 for cases with regression data. Clinicopathologic factors were correlated with overall and first‐site of recurrence and with recurrence‐free survival (RFS).ResultsThere were 4790 patients and the median follow‐up was 39.6 months. Regression and recurrences were seen in 1081 (22.6%) and 773 (16.1%) cases, respectively. First‐site locoregional and distant recurrences were seen in 412 (8.6%) and 352 (7.3%) patients, respectively. Regression was seen in 15.8% and 24.7% of all cases with and without recurrences (p < 0.0001), respectively, while regression was seen in 14.3% and 17.9% of first‐site locoregional and distant recurrent cases, respectively, compared with 23.3% and 22.9% of patients with regression and without first‐site locoregional and distant recurrences, respectively (p = 0.29). On multivariable analysis, after controlling for age, gender, thickness, ulceration, lymphovascular invasion, and sentinel lymph node status, regression significantly predicted improved RFS (p = 0.004) and fewer first‐site regional recurrences (p = 0.017).ConclusionOur data suggest that regression is a favorable prognostic marker in melanoma and predicts significantly better RFS and decreased first‐site regional recurrences.

Abstract Background: Young doctors have made up a substantial part of healthcare forces during the Coronavirus Disease 2019 (COVID-19) pandemic. The aim of this study was to determine the rate and level of psychological distress among young doctors during the COVID-19 outbreak. Methods: This cross-sectional cohort study, dedicated to doctors, at or below the age of 40, was conducted in 62 countries as an online survey between September – November 2020. Survey questions covered the following areas: 1. demographics 2. work environment 3.the ‘Hospital Anxiety and Depression Scale (HADS)’ and the ‘Perceived Stress Scale 10 (PSS-10)’. The primary outcome was the rate and level of anxiety/depression and stress among surveyed population defined according to adopted cut off values (HADS>13, PSS-10>14). Secondary outcomes included risk factors for increased HADS and PSS-10 scores.Results: Among 1186 respondents, median aged 32 [29–36], 675 (44.5%) females, 96% reported a high level of anxiety/depression and 97% reported a high level of stress. Factors associated with significantly higher scores for anxiety/depression were increased work hours [OR 1.61 95%CI (1.12–2.34);p=0.01] and loss of pay [OR 5.53, 95% CI (1.57–19.47);p=0.008], while reduced work hours [OR 0.68 95% CI (0.48 - 0.98);p=0.03], increased salaries [OR 0.54 95% CI (0.35–0.85);p=0.003) and good training [OR 0.99 95%CI (0.99– 1.00);p=0.002] were associated with lower scores. Higher scores for stress were associated with higher professional experience [OR 1.08 95% CI (1.02–1.14);p=0.008], reduced salaries [OR 1.74 95% CI (1.01–2.92);p=0.04] and living with a partner [OR 1.53 95% CI (1.08–2.17);p=0.01]. Conclusions: A high rate of young doctors working clinically during the COVID-19 pandemic reported a persistently high level of psychological distress more than six months after the initial outbreak. Improvements in work organization, including reduced work hours and financial security are essential to prevent further psychological suffering among young doctors worldwide.