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Category: Ankle; Hindfoot; Trauma Introduction/Purpose: Prosthetic substitution of the talus presents a unique challenge to the foot and ankle surgeon. The shear and compressive forces on the talus and its tenuous blood supply lead to high rates of avascular necrosis with possible talar collapse. The purpose of this systematic review is to evaluate whether total talus replacements (TTR) lead to improved clinical outcomes with appropriate safety metrics in patients with a history of avascular necrosis or significant trauma. Methods: Concepts of talus and arthroplasty were searched in MEDLINE (PubMed), Embase (Elsevier), CINAHL Complete (EBSCOhost), and Scopus (Elsevier) from the database's inception through November 4, 2021. Inclusion Criteria were 1) previous trauma to the talus, 2) post-traumatic or degenerative arthritis to the tibiotalar joint, 3) avascular necrosis of talus, 4) multiple failed prior interventions, 5) degenerative osteoarthritis to the tibiotalar joint, and 56) inflammatory arthropathy to tibiotalar joint. Manuscripts in non-English languages or those with concomitant total ankle arthroplasty or revision arthroplasty were excluded. All study designs were eligible according to the Journal of Bone and Joint Surgery criteria level I-IV. The modified Coleman Methodology Score was used to evaluate study quality and the Methodological Index for Non-Randomized Studies criteria was used to assess risk of bias. Results: Twenty-two studies of 191 patients (196 tali) at an average age of 50 (14-80) years were included (Figure 1a). Nineteen studies utilized third generation implants, two studies used first generation (n=9), and one study used second generation implants (n = 14) made of ceramic (n=82), cobalt chrome (n=49), or titanium (n=23) (Figure 1b). Radiographic and patient-reported outcomes are outlined in Figure 1c. The most common adverse outcome was osteosclerosis of the tibia (n=24), calcaneus (n=19), and navicular (n=5). Additionally, hindfoot varus (n=3), ankle discomfort (n = 3), decreased subtalar motion (n=7), periprosthetic fracture (n=1), calcaneal fracture (n=1), delayed wound healing (n=3), hindfoot valgus (n=1), prosthetic stem sunken into the talar neck (n=1), superficial peroneal nerve neuroma (n=1), loosening (n=2) were reported. Eight revisions were reported. Conclusion: TTR is an appealing option to maintain range of motion through the tibiotalar joint and allow for maintenance of more normal foot and ankle biomechanics. Given promising early- and mid-term outcomes, TTR is becoming more widely used in the setting of talar collapse. Still, high complication rates, especially adjacent joint osteoarthritis, may remain under-reported in the literature given inadequate long-term follow-up. Future research should aim to expand upon the indications of TTR, elucidate survivorship and complication rates, and directly compare TTR to existing forms of salvage options for advanced talar avascular necrosis.

The volume of outpatient total knee arthroplasty (TKA) has increased with advances in perioperative protocols, patient selection, and recent policy changes regarding insurance authorization. This study analyzed 30-day outcomes from a national database to better understand risk factors for delayed discharge (length of stay [LOS] ≥1), readmission, and reoperation after outpatient TKA.The National Surgical Quality Improvement Program (NSQIP) database was utilized to collect TKA (CPT 27447) billed as outpatient surgery performed from 2013 to 2018. Patient demographics, comorbidities, and short-term outcomes were collected and compared in LOS 0 versus LOS ≥1 cohorts. Subgroup analysis was completed for TKA performed in 2018, after the Center for Medicare Services removal of TKA from the inpatient-only list.A total of 13,669 patients had outpatient TKA performed from 2013 to 2018. Most patients had LOS ≥1 day (77.1%). The LOS 0 cohort demonstrated a lower 30-day readmission rate (1.8%) compared to LOS ≥1 (2.8%), P.01. Both groups demonstrated a low 30-day reoperation rate, LOS 0 (0.7%) and LOS ≥1 (1.1%), P = .05. Regression analysis demonstrated risk factors for LOS ≥1 day included COPD, ASA ≥3, age75, and BMI35 kg/mRisk factors for LOS ≥1 day include age75, ASA ≥3, BMI35 kg/m

Individuals with psychiatric disorders are at increased risk of age-related diseases and early mortality. Recent studies demonstrate that this link between mental health and aging is reflected in epigenetic clocks, aging biomarkers based on DNA methylation. The reported relationships between epigenetic clocks and mental health are mostly correlational, and the mechanisms are poorly understood. Here, we review recent progress concerning the molecular and cellular processes underlying epigenetic clocks as well as novel technologies enabling further studies of the causes and consequences of epigenetic aging. We then review the current literature on how epigenetic clocks relate to specific aspects of mental health, such as stress, medications, substance use, health behaviors, and symptom clusters. We propose an integrated framework where mental health and epigenetic aging are each broken down into multiple distinct processes, which are then linked to each other, using stress and schizophrenia as examples. This framework incorporates the heterogeneity and complexity of both mental health conditions and aging, may help reconcile conflicting results, and provides a basis for further hypothesis-driven research in humans and model systems to investigate potentially causal mechanisms linking aging and mental health.

Background Total shoulder arthroplasty (TSA) is the gold standard treatment of end-stage glenohumeral osteoarthritis. TSA with stemless humeral implants have shown comparable rates of success to stemmed components. Prolonged operative time is associated with increased cost, surgical, and medical complications, and higher rates of infection. Therefore, the goal of this study was to evaluate operative time with stemless TSA compared to stemmed TSA. We hypothesize that stemless TSA will be associated with less operative than stemmed TSA. Methods In this retrospective case-control study of 80 consecutive patients, 40 patients underwent stemless TSA and 40 patients underwent stemmed TSA. To eliminate potential bias due to individual surgeons surgical techniques, the cohorts were matched by surgeon in a 1:1 ratio. Only primary TSA, without augmented glenoid implants, were included. We evaluated the difference in operative time between groups. Operative time was defined as time from incision to commencement of wound closure. Results Our sample included 62.5% and 55% females in the stemmed and stemless cohorts respectively. Patients in the stemless group were noted to be younger with a mean age of 61 compared to 68 in the stemmed group (P Conclusion In this case-control study, matched by surgeon to avoid technique bias, evaluating stemmed and stemless humeral components for anatomic TSA, we noted a significantly shorter operative time in favor of stemless TSA. The clinical and economic impact of this difference remains unclear.

BACKGROUND: Aortic root evaluation is conventionally based on two-dimensional measurements at a single phase of the cardiac cycle. This work presents an image analysis method for assessing dynamic three-dimensional changes in the aortic root of minimally calcified bicuspid aortic valves (BAVs) with and without moderate to severe aortic regurgitation. METHODS: The aortic root was segmented over the full cardiac cycle in three-dimensional transesophageal echocardiographic images acquired from 19 patients with minimally calcified BAVs and from 16 patients with physiologically normal tricuspid aortic valves (TAVs). The size and dynamics of the aortic root were assessed using the following image-derived measurements: absolute mean root volume and mean area at the level of the ventriculoaortic junction, sinuses of Valsalva, and sinotubular junction, as well as normalized root volume change and normalized area change of the ventriculoaortic junction, sinuses of Valsalva, and sinotubular junction over the cardiac cycle. RESULTS: Normalized volume change over the cardiac cycle was significantly greater in BAV roots with moderate to severe regurgitation than in normal TAV roots and in BAV roots with no or mild regurgitation. Aortic root dynamics were most significantly different at the mid-level of the sinuses of Valsalva in BAVs with moderate to severe regurgitation than in competent TAVs and BAVs. CONCLUSIONS: Echocardiographic reconstruction of the aortic root demonstrates significant differences in dynamics of BAV roots with moderate to severe regurgitation relative to physiologically normal TAVs and competent BAVs. This finding may have implications for risk of future dilatation, dissection, or rupture, which warrant further investigation.

To evaluate changes in health-related and vision-related quality of life (VRQoL) among patients with noninfectious uveitis who were treated with antimetabolites.Secondary analysis of a randomized controlled trial.Patients with noninfectious uveitis from India, the United States, Australia, Saudi Arabia, and Mexico.From 2013 through 2017, 216 participants were randomized to receive 25 mg weekly oral methotrexate or 1.5 g twice daily oral mycophenolate mofetil. Median changes in quality of life (QoL) were measured using Wilcoxon signed-rank tests, and differences between treatment groups were measured using linear mixed models, adjusting for baseline QoL score, age, gender, and site. Among Indian patients, VRQoL scores from a general scale (the National Eye Institute Visual Function Questionnaire [NEI-VFQ]) and a culturally specific scale (the Indian Visual Function Questionnaire [IND-VFQ]) were compared using Pearson correlation tests.Vision-related QoL (NEI-VFQ and IND-VFQ) and health-related QoL (HRQoL; physical component score [PCS] and mental component score [MCS] of the Medical Outcomes Study 36-Item Short Form Survey [SF-36v2]) were measured at baseline, the primary end point (6 months or treatment failure before 6 months), and the secondary end point (12 months or treatment failure between 6 and 12 months).Among 193 participants who reached the primary end point, VRQoL increased from baseline by a median of 12.0 points (interquartile range [IQR], 1.0-26.1, NEI-VFQ scale), physical HRQoL increased by a median of 3.6 points (IQR, -1.4 to 14.9, PCS SF-36v2), and mental HRQoL increased by a median of 3.0 points (IQR, -3.7 to 11.9, MCS SF-36v2). These improvements in NEI-VFQ, SF-36v2 PCS, and SF-36v2 MCS scores all were significant (P0.01). The linear mixed models showed that QoL did not differ between treatment groups for each QoL assessment (NEI-VFQ, IND-VFQ, PCS SF-36v2, and MCS SF-36v2; P0.05 for all). The NEI-VFQ and IND-VFQ scores for Indian participants were correlated highly at baseline and the primary and secondary end points (correlation coefficients, 0.87, 0.80, and 0.90, respectively).Among patients treated with methotrexate or mycophenolate mofetil for uveitis, VRQoL and HRQoL improved significantly over the course of 1 year and did not differ by treatment allocation. These findings suggest that antimetabolites could improve overall patient well-being and daily functioning.

Background Low temperature bonding is the key for developing advanced electronic packaging technique. While Cu is regarded as a promising material for interconnects with high conductivity, the oxidation issue during processing needs to be solved. Methods In this study, Cu-to-Cu direct bonding was achieved at low temperature without applying pressure by a green chemical method. Synthesized Cu nanoparticles (NPs) without capping agents were mixed with polyethylene glycol (PEG). Significant findings An iterating mechanism is proposed as Cu oxide catalyzing the decomposition of PEG, and the decomposed products further reduce the Cu oxide. Particle size and size distribution of Cu NPs were simply controlled by pH value of the reducing solution. A random close packing model proves that packing density of the pre-sintered Cu NPs directly correlates to bonding strength. Ductile fracture surface confirms the realization of well-sintered joints by a green process that can be applied to devices.

Purpose To determine classification criteria for multifocal choroiditis with panuveitis (MFCPU) DESIGN: : Machine learning of cases with MFCPU and 8 other posterior uveitides. Methods Cases of posterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the posterior uveitides. The resulting criteria were evaluated on the validation set. Results One thousand sixty-eight cases of posterior uveitides, including 138 cases of MFCPU, were evaluated by machine learning. Key criteria for MFCPU included: 1) multifocal choroiditis with the predominant lesions size >125 µm in diameter; 2) lesions outside the posterior pole (with or without posterior involvement); and either 3) punched-out atrophic chorioretinal scars or 4) more than minimal mild anterior chamber and/or vitreous inflammation. Overall accuracy for posterior uveitides was 93.9% in the training set and 98.0% (95% confidence interval 94.3, 99.3) in the validation set. The misclassification rates for MFCPU were 15% in the training set and 0% in the validation set. Conclusions The criteria for MFCPU had a reasonably low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

Purpose To determine classification criteria for sarcoidosis-associated uveitis DESIGN: Machine learning of cases with sarcoid uveitis and 15 other uveitides. Methods Cases of anterior, intermediate, and panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were analyzed by anatomic class, and each class was split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training sets to determine a parsimonious set of criteria that minimized the misclassification rate among the intermediate uveitides. The resulting criteria were evaluated on the validation sets. Results One thousand eighty-three anterior uveitides, 589 intermediate uveitides, and 1012 panuveitides, including 278 cases of sarcoidosis-associated uveitis, were evaluated by machine learning. Key criteria for sarcoidosis-associated uveitis included a compatible uveitic syndrome of any anatomic class and evidence of sarcoidosis, either 1) a tissue biopsy demonstrating non-caseating granulomata or 2) bilateral hilar adenopathy on chest imaging. The overall accuracy of the diagnosis of sarcoidosis-associated uveitis in the validation set was 99.7% (95% confidence interval 98.8, 99.9).The misclassification rates for sarcoidosis-associated uveitis in the training sets were: anterior uveitis 3.2%, intermediate uveitis 2.6%, and panuveitis 1.2%; in the validation sets the misclassification rates were: anterior uveitis 0%, intermediate uveitis 0%, and panuveitis 0%, respectively. Conclusions The criteria for sarcoidosis-associated uveitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

Purpose To determine classification criteria for birdshot chorioretinitis. Design Machine learning of cases with birdshot chorioretinitis and 8 other posterior uveitides. Methods Cases of posterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the infectious posterior/panuveitides. The resulting criteria were evaluated on the validation set. Results One thousand sixty-eight cases of posterior uveitides, including 207 cases of birdshot chorioretinitis, were evaluated by machine learning. Key criteria for birdshot chorioretinitis included a multifocal choroiditis with: 1) the characteristic appearance a bilateral multifocal choroiditis with cream-colored or yellow-orange, oval or round choroidal spots ("birdshot" spots); 2) absent to mild anterior chamber inflammation; and 3) absent to moderate vitreous inflammation; or multifocal choroiditis with positive HLA-A29 testing and either: 1) classic "birdshot spots" or 2) characteristic imaging on indocyanine green angiography. Overall accuracy for posterior uveitides was 93.9% in the training set and 98.0% (95% confidence interval 94.3, 99.3) in the validation set. The misclassification rates for birdshot chorioretinitis were 10% in the training set and 0% in the validation set. Conclusions The criteria for birdshot chorioretinitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

Quantifying biological aging is critical for understanding why aging is the primary driver of morbidity and mortality and for assessing novel therapies to counter pathological aging. In the past decade, many biomarkers relevant to brain aging have been developed using various data types and modeling techniques. Aging involves numerous interconnected processes, and thus many complementary biomarkers are needed, each capturing a different slice of aging biology. Here we present a hierarchical framework highlighting how these biomarkers are related to each other and the underlying biological processes. We review those measures most studied in the context of brain aging: epigenetic clocks, proteomic clocks, and neuroimaging age predictors. Many studies have linked these biomarkers to cognition, mental health, brain structure, and pathology during aging. We also delve into the challenges and complexities in interpreting these biomarkers and suggest areas for further innovation. Ultimately, a robust mechanistic understanding of these biomarkers will be needed to effectively intervene in the aging process to prevent and treat age-related disease.

PURPOSE: To evaluate long-term efficacy and safety of extended treatment with adalimumab in patients with noninfectious intermediate, posterior, or panuveitis.DESIGN: Open-label, multicenter, phase 3 extension study (VISUAL III).PARTICIPANTS: Adults who had completed a randomized, placebo-controlled phase 3 parent trial (VISUAL I or II) without treatment failure (inactive uveitis) or discontinued after meeting treatment failure criteria (active uveitis).METHODS: Patients received subcutaneous adalimumab 40 mg every other week. Data were collected for ≤362 weeks. Adverse events (AEs) were recorded until 70 days after the last dose of study drug.MAIN OUTCOME MEASURES: Main outcome measures were long-term safety and quiescence; other efficacy variables included inflammatory lesions, anterior chamber cell and vitreous haze grade, macular edema, visual acuity, and dose of uveitis-related corticosteroids.RESULTS: Of 424 patients enrolled, 67% (283/424) had active uveitis and 33% (141/424) had inactive uveitis at study entry; 60 patients subsequently met exclusion criteria, and 364 patients were included in the intent-to-treat analysis. Efficacy variables were analyzed through week 150 when approximately 50% of patients (214/424) remained in the study. The percentage of patients in quiescence increased from 34% (122/364) at week 0 to 85% (153/180) at week 150. Corticosteroid-free quiescence was achieved by 54% (66/123) and 89% (51/57) of patients with active or inactive uveitis at study entry, respectively, by week 150. Mean daily dose of corticosteroids was reduced from 9.4±17.1 mg/day at week 0 (n=359) to 1.5±3.9 mg/day at week 150 (n=181). The percentage of patients who achieved other efficacy variables increased over time for those with active uveitis at study entry and was maintained for those with inactive uveitis. The most frequently reported treatment-emergent AEs of special interest for adalimumab were infections (n=275; 78.7 events/100 patient-years); AEs and serious AEs occurred at a rate of 396 events/100 patient-years and 15 events/100 patient-years, respectively.CONCLUSIONS: Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and maintenance of quiescence for those with inactive uveitis. AEs were comparable to those reported in the parent trials and consistent with the known safety profile of adalimumab.

Uveitis is a heterogeneous collection of diseases. We tested the hypothesis that despite the diversity of uveitides, there could be common mechanisms shared by multiple subtypes, and that evidence of these common mechanisms may be detected as gene expression profiles in whole blood.Cohort study.Ninety subjects with uveitis including axial spondyloarthritis (n = 17), sarcoidosis (n = 13), inflammatory bowel disease (n = 12), tubulointerstitial nephritis with uveitis (n = 10), or idiopathic uveitis (n = 38) as well as 18 healthy controls were enrolled, predominantly at Oregon HealthScience University. RNA-Seq data generated from peripheral, whole blood identified 19,859 unique transcripts. We analyzed gene expression pathways via Kyoto Encyclopedia of Genes and Genomes and Gene Ontology (GO). We validated our list of upregulated genes by comparison to a previously published study on peripheral blood gene expression among 50 subjects with diverse forms of uveitis.Both the Kyoto Encyclopedia of Genes and Genomes and GO analysis identified multiple shared pathways or GO terms with a P value of.0001. Almost all pathways related to the immune response and/or response to an infection. A total of 119 individual transcripts were upregulated by at least 1.5-fold and false discovery rate.05, and 61 were downregulated by similar criteria. Comparing mRNA from our study with a false discovery rate.05 and the prior report, we identified 10 common gene transcripts: ICAM1, IL15RA, IL15, IRF1, IL10RB, GSK3A, TYK2, MEF2A, MEF2B, and MEF2D.Many forms of uveitis share overlapping mechanisms. These data support the concept that a single therapeutic approach could benefit diverse forms of this disease.