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The possible mechanisms of action of bovine pancreatic ribonuclease are discussed in the light of the detailed knowledge of the geometry of the active site that has been derived from studies of inhibitor binding by X-ray diffraction and nuclear magnetic resonance. When combined with a knowledge of the mechanism of phosphate ester hydrolysis, this information imposes severe geometric constraints on possible mechanisms of action of the enzyme. Two types of mechanism can be distinguished, the linear and the pseudorotation. The linear mechanism includes a catalytic role for both histidine residues at the active site and does not involve pseudorotation of the intermediate. In contrast, in the pseudorotation mechanism one histidine residue performs all the catalytic functions, while the other serves only to bind the phosphate anion; this necessarily involves pseudorotation of the intermediate and specific protonation of the leaving group by the enzyme. The mode of binding of the product of the reaction, cytidine-3'-monophosphate, has been elucidated by X-ray diffraction and nuclear magnetic resonance. If the substrate binds in an analogous way, only the linear mechanism is possible. This mechanism is described in detail.

The incidence of adoption disruptions is much higher in special-needs adoptions than in infant adoptions. This article reports the results of an analysis of differences in functioning between families able to sustain special-needs placements and families in which they disrupted. The finding is that the father plays a pivotal role in maintaining these placements. If he is actively involved in parenting, and able to nurture and support the mother in her role, placements are more likely to be sustained. [ABSTRACT FROM AUTHOR]

The vacuolar H + -ATPase (V-ATPase) is a functionally conserved multimeric complex localized at the membranes of many organelles where its proton-pumping action is required for proper lumen acidification. The V-ATPase complex is composed of several subunits, some of which have been linked to human disease. We and others previously reported pathogenic dominantly acting variants in ATP6V1B2, the gene encoding the V1B2 subunit, as underlying a clinically variable phenotypic spectrum including dominant deafness-onychodystrophy (DDOD) syndrome, Zimmermann-Laband syndrome, and deafness, onychodystrophy, osteodystrophy, intellectual disability, and seizures (DOORS) syndrome. Here, we report on an individual with features fitting DOORS syndrome caused by dysregulated ATP6V1C1 function, expand the clinical features associated with ATP6V1B2 pathogenic variants, and provide evidence that these ATP6V1C1/ATP6V1B2 amino acid substitutions result in a gain-of-function mechanism upregulating V-ATPase function that drives increased lysosomal acidification. We demonstrate a disruptive effect of these ATP6V1B2/ATP6V1C1 variants on lysosomal morphology, localization and function, resulting in a defective autophagic flux and accumulation of lysosomal substrates. We also show that the upregulated V-ATPase function affects cilium biogenesis, further documenting pleiotropy. This work identifies ATP6V1C1 as a new gene associated with a neurodevelopmental phenotype resembling DOORS syndrome, documents the occurrence of a phenotypic continuum between ZLS, and DDOD and DOORS syndromes, and classify these conditions as lysosomal disorders., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Excessive daytime sleepiness (EDS) is a disabling symptom of Lewy body disorders (LBD). The hypothalamus is a key sleep-wake regulator, but its contribution to EDS in LBD remains unclear., Objectives: Use diffusion MRI to evaluate the relationship of hypothalamic microstructure to EDS symptoms in LBD., Methods: We studied 102 patients with clinically-defined LBD (Parkinson's disease, n=93; Parkinson's disease dementia, n=4; and dementia with Lewy bodies, n=5) and Epworth Sleepiness Scale (ESS) within 2 years of MRI. Mean diffusivity (MD) was compared between EDS+ (ESS≥10, n=37) and EDS- (ESS<10, n=65) groups in the whole hypothalamus and three subregions, covarying for age and sex. Secondary analyses tested correlations between subregion MD and continuous ESS, global cognition, and motor scores; and between subregion volume and continuous ESS., Results: MD was increased in EDS+ compared to EDS- only in the inferior tuberal subregion (Cohen's d=0.43, p=0.043, β=0.117±0.057), with trend level differences in the whole hypothalamus (Cohen's d=0.39, p=0.064, β=0.070±0.037) and superior tuberal subregion (Cohen's d=0.38, p=0.073, β=0.063±0.035). No difference was seen in the posterior subregion (Cohen's d=0.1, p=0.628, β=0.019±0.038). Significant correlations with continuous ESS were seen in MD of whole hypothalamus (r 2 =0.074, p=0.0057), superior tuberal (r 2 =0.081, p=0.0038), and inferior tuberal (r 2 =0.073, p=0.0059) subregions. There was no correlation of hypothalamic MD with global cognition or motor scores, and no correlation of whole/subregional hypothalamic volumes with ESS., Conclusions: Daytime sleepiness associates with increased MD in the inferior tuberal hypothalamus in an LBD cohort. This suggests degeneration within this region could contribute to EDS symptoms.

Firearm injuries are the leading cause of death among children and adolescents in the US. Safe storage of firearms in the home is one of the most effective ways of preventing firearm injuries in children. This feasibility study was conducted in both the pediatric and general Emergency Departments of a large urban academic medical center in a community with high rates of firearm injuries in children. The objective was to pilot a survey seeking to describe sociodemographic characteristics, firearm specific risk factors, and firearm storage practices of households with children in the community. One hundred participants completed a survey containing items regarding participant demographics, household features, firearm ownership, firearm characteristics, and storage practices. Descriptive statistics were used to define sociodemographic characteristics of the enrolled population, comparing those with firearms to those without, and to describe firearms and storage practices of firearm owners in households with children. Of 100 participants, 30 lived in households with firearms and children. Most firearms in homes with children were stored locked and unloaded most of the time; however, 30% of participants with firearms and children in the home reported not consistently storing a firearm locked and unloaded. The most common reason given for not storing a firearm in the safest manner possible was that storing a firearm locked and unloaded would make it difficult to access quickly. Engaging families with children in discussions around firearm prevention during Emergency Department visits is feasible and may have implications for future efforts to promote safe firearm storage practices., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Osteoporosis treatment following arthroplasty for femoral neck fracture (FNF) is associated with lower rates of periprosthetic fracture (PPF). Our study evaluated the economic viability of treatment in patients following arthroplasty and demonstrates that treatment with oral bisphosphonates can be cost-effective in preventing PPF., Introduction: Osteoporosis treatment following arthroplasty for femoral neck fracture (FNF) is associated with lower rates of periprosthetic fracture (PPF). Although cost-effective in reducing the rate of secondary fragility fracture, the economic viability of osteoporosis treatment in preventing PPF has not been evaluated. Therefore, the purpose of this study is to use a break-even analysis to determine whether and which current osteoporosis medications are cost-effective in preventing PPF following arthroplasty for FNFs., Methods: Three-year average cost of osteoporosis medication (oral bisphosphonates, estrogen hormonal therapy, intravenous (IV) bisphosphonates, denosumab, teriparatide, and abaloparatide), costs of PPF care, and PPF rates in patients who underwent hip arthroplasty for FNFs without osteoporosis treatment were used to perform a break-even analysis. The absolute risk reduction (ARR) related to osteoporosis treatment and sensitivity analyses were used to evaluate the cost-effectiveness of this intervention and break-even PPF rates., Results: Oral bisphosphonate therapy following arthroplasty for hip fractures would be economically justified if it prevents one out of 56 PPFs (ARR, 1.8%). Given the current cost and incidence of PPF, overall treatment can only be economically viable for PPF prophylaxis if the 3-year costs of these agents are less than $1500., Conclusion: The utilization of lower cost osteoporosis medications such as oral bisphosphonates and estrogen hormonal therapy as PPF prophylaxis in this patient population would be economically viable if they reduce the PPF rate by 1.8% and 1.5%, respectively. For IV bisphosphonates and newer agents to be economically viable as PPF prophylaxis in the USA, their costs need to be significantly reduced., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Background and Objectives: Suicide is a leading cause of death among youth in the United States. Pediatric emergency department visits for non-psychiatric concerns present an opportunity to identify youth at risk for suicidality. This quality improvement initiative was undertaken to ensure that those patients identified as low risk for suicide receive resources, bridging the gap between identifying at-risk youth and providing them with appropriate follow up mental health resources. The aim of this project was to increase the proportion of after visit summaries containing mental health resources by 25 % within 6 months for medical patients who are found to have non-acute low suicide risk and are discharged from the emergency department., Methods: The primary outcome measure was the proportion of discharged medical patients who screened positive for suicidal ideation and were determined to be at low risk for suicide who received mental health resources on discharge before and after intervention. A multidisciplinary team targeted the following 3 key drivers: 1) multidisciplinary engagement 2) training and education of providers and 3) health information technology. Plan, Do, Study and Act cycles included the following: 1) an educational campaign with regular multidisciplinary meetings, educational updates, and email reminders; 2). an electronic health record change; and 3) An individual report to providers., Results: After the intervention, the percentage of medical patients with low-risk suicidality being discharged with mental health resources increased by more than 70 %., Conclusions: A champion led multidisciplinary team, using PDSA methodology, can implement sustained improvements in mental health resource distribution., Competing Interests: Declaration of competing interest The authors have no potential conflicts of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Prior studies have demonstrated HIV does not increase the risk of 2-year complications following TKA; however, the literature is sparse regarding the impact of HIV and AIDS on long-term implant survivorship. The purpose of this study was to compare the 10-year cumulative incidence and risk of revision TKA in patients with and without asymptomatic HIV, and with and without AIDS., Methods: Patients with HIV who underwent elective TKA were identified using a national database and divided into subgroups of asymptomatic HIV (AHIV) and acquired immunodeficiency syndrome (AIDS). These patients with HIV were propensity matched based on age, sex, and Charlson Comorbidity Index (CCI) to a control group of elective TKA patients without HIV in a 1:2 ratio. Patients were also compared to an unmatched control group., Results: The 10-year risk for all-cause revision TKA was higher in the HIV group compared to unmatched controls (HR 1.40, 95% CI 1.02-1.93, p = 0.038) but not matched controls (HR 1.13, 95% CI 0.77-1.63, p = 0.594). When compared to both control groups (unmatched; matched), the AIDS group had a higher risk of 10-year all-cause revision (HR 2.74, 95% CI 1.51-4.99, p < 0.001; HR 2.19, 95% CI 1.17-4.11, p = 0.014), dislocation/instability (HR 4.89, 95% CI 1.54-15.51, p = 0.007; HR 3.86, 95% CI 1.12-13.34, p = 0.033), and periprosthetic fracture [PPF] (HR 0.67, 95% CI 0.16-2.74, p = 0.002; HR 3.82, 95% CI 1.08-13.45, p = 0.037). However, patients with AIDS were not at increased risk of PJI or mechanical loosening compared to unmatched controls or matched controls., Discussion: This study expands on current literature by following a nationwide cohort of HIV/AIDS patients for 10 years after TKA. Although a diagnosis of asymptomatic HIV was not associated with increased risk of 10-year revision rates following TKA, a diagnosis of AIDS was. Surgeons should ensure patients' serum CD4 level is sufficient, ideally in the normal range of 500-1500 cells per mm 3 , before undergoing TKA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Bariatric surgery (BS) is indicated for select class III obesity patients undergoing total knee arthroplasty (TKA) to reduce obesity-related complications. This study assessed the effect of BS on TKA revision rates compared to the general population and class III obesity patients without a history of BS., Methods: A national database identified patients who had primary TKA. They were divided into two groups: those with BS prior to TKA and those without. Patients without BS formed two control groups, a matched general population, and a matched class III obese cohort. The BS group was matched with controls based on age, Charlson Comorbidity Index (CCI), gender, and diabetes mellitus. Revision rates were analyzed using Kaplan-Meier survival analysis and hazard ratios (HR), calculated using Cox proportional hazard modeling., Results: 14,292 BS patients were compared to 57,006 matched general population controls, and 19,504 BS patients were compared to 77,846 matched class III obesity control patients. BS patients had a higher risk of 5-year all-cause revision (HR: 1.13; P = 0.014) and revision due to periprosthetic fracture (HR: 1.39; P < 0.001) compared to the general population. Compared to class III obesity controls, BS patients had a lower risk of 5-year revision due to prosthetic joint infection (HR: 0.77; P = 0.001), with no difference in all-cause revision (P = 0.362)., Conclusion: BS does not reduce all-cause TKA revision risk compared to the general or matched class III obesity population. However, it lowers the risk of revision due to prosthetic joint infection when compared to patients with class III obesity., Level of Evidence: IV., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Savyasachi C Thakkar is an unpaid consultant for KCI and OrthoAlign, editorial/governing board for Arthroplasty Today and Journal of Arthroplasty and Board Member of American Association of Hip and Knee Surgeons. Gregory J Golladay is a recipient of royalties from Stryker and Arthroplasty Today, editorial/governing board for Arthroplasty Today and Journal of Arthroplasty and Board Member of American Association of Hip and Knee Surgeons and Virginia Orthopaedic Society.]., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: There is no clear research showcasing bariatric surgery's (BS's) impact on long-term surgical complications following total hip arthroplasty (THA). Therefore, this study compared the 10-year cumulative incidence and risk of revision following THA in patients who underwent BS when compared to the general population and class III obesity patients who did not undergo BS., Methods: Patients who underwent elective THA from 2010 to 2021 were identified using an all-payer claims database. Patients who underwent BS prior to THA were separately matched to a control of the general population and those who had class III obesity (body mass index ≥40) by age, sex, Charlson Comorbidity Index, and diabetes using a 1:4 ratio. Kaplan-Meier analyses generated 10-year cumulative incidence rates, and a Cox proportional hazard ratio (HR) model generated HRs and 95% confidence intervals (CIs)., Results: When compared to the general control, patients who have a history of BS had an elevated 10-year risk of all-cause revision (HR 1.31, 95% CI: 1.16 to 1.47, P < .001), prosthetic joint infection (HR: 1.62, CI: 1.30 to 2.04; P < .001), mechanical loosening (HR: 1.20, CI: 1.01 to 1.44; P = .040), and dislocation/instability (HR: 1.35, CI: 1.09 to 1.68; P = .007). There was no difference in the 10-year risk of all-cause revision or other indications for revision in the BS cohort compared to the matched class III obesity cohort (P = .142)., Conclusions: Those who underwent BS before THA had comparable 10-year revision rates when compared to those who had class III obesity and higher rates compared to the general population. This suggests BS may not reduce the 10-year surgical risks associated with obesity when compared to a class III obese surgical population., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Bilateral simultaneous total knee arthroplasty (BSTKA) has decreased in frequency due to concerns about higher rates of early mortality and complications than unilateral or staged surgeries. Purpose : We sought to evaluate whether technology assistance (encompassing robotics and computer assistance) decreases early mortality following BSTKA. Methods : We conducted a retrospective cohort study using a national all-payer claims database. Patients who underwent BSTKA from October 2015 to December 2020 were identified. Univariate and multivariable analyses were conducted to compare outcomes in patients who underwent BSTKA with technology assistance compared to conventional instrumentation. The primary outcome was 30-day postoperative mortality. Secondary outcomes were respiratory failure and fat embolism. A post-hoc analysis was performed to evaluate length of stay, readmission, and other medical complications. Results : A total of 14,870 patients who underwent BSTKA were included in this study. Of these, 860 patients underwent technology-assisted BSTKA, and 14,010 patients underwent BSTKA without technology assistance. After a multivariable analysis, patients who underwent technology-assisted BSTKA had equivalent odds of 30-day mortality compared to those who underwent BSTKA without technology assistance. Technology assistance was not protective against the development of acute respiratory failure or fat embolism. Conclusion : This retrospective cohort study found no differences in the rates of 30-day mortality, respiratory failure, or fat embolism after technology-assisted BSTKA compared to conventional BSTKA. On the post-hoc analysis, technology use was associated with a decreased length of stay, lower readmission risk, and decreased rates of deep vein thrombosis, pulmonary embolism, and blood transfusion., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Gregory Golladay, MD, reports relationships with Stryker, GLG, Cuerus, Arthroplasty Today, Journal of Arthroplasty, American Association of Hip and Knee Surgeons, and Virginia Orthopaedic Society. Savyasachi Thakkar, MD, reports relationships with KCI, OrthoAlign, Arthroplasty Today, Journal of Arthroplasty, and American Association of Hip and Knee Surgeons. The other authors declare no potential conflicts of interest., (© The Author(s) 2023.)

The Rab family of guanosine triphosphatases (GTPases) includes key regulators of intracellular transport and membrane trafficking targeting specific steps in exocytic, endocytic, and recycling pathways. DENND5B (Rab6-interacting Protein 1B-like protein, R6IP1B) is the longest isoform of DENND5, an evolutionarily conserved DENN domain-containing guanine nucleotide exchange factor (GEF) that is highly expressed in the brain. Through exome sequencing and international matchmaking platforms, we identified five de novo variants in DENND5B in a cohort of five unrelated individuals with neurodevelopmental phenotypes featuring cognitive impairment, dysmorphism, abnormal behavior, variable epilepsy, white matter abnormalities, and cortical gyration defects. We used biochemical assays and confocal microscopy to assess the impact of DENND5B variants on protein accumulation and distribution. Then, exploiting fluorescent lipid cargoes coupled to high-content imaging and analysis in living cells, we investigated whether DENND5B variants affected the dynamics of vesicle-mediated intracellular transport of specific cargoes. We further generated an in silico model to investigate the consequences of DENND5B variants on the DENND5B-RAB39A interaction. Biochemical analysis showed decreased protein levels of DENND5B mutants in various cell types. Functional investigation of DENND5B variants revealed defective intracellular vesicle trafficking, with significant impairment of lipid uptake and distribution. Although none of the variants affected the DENND5B-RAB39A interface, all were predicted to disrupt protein folding. Overall, our findings indicate that DENND5B variants perturb intracellular membrane trafficking pathways and cause a complex neurodevelopmental syndrome with variable epilepsy and white matter involvement., Competing Interests: Declaration of interests A.C. is an employee of GeneDx, LLC. The Department of Molecular and Human Genetics at Baylor College of Medicine receives revenue from clinical genetic testing completed at Baylor Genetics Laboratories., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: ACTN2, encoding alpha-actinin-2, is essential for cardiac and skeletal muscle sarcomeric function. ACTN2 variants are a known cause of cardiomyopathy without skeletal muscle involvement. Recently, specific dominant monoallelic variants were reported as a rare cause of core myopathy of variable clinical onset, although the pathomechanism remains to be elucidated. The possibility of a recessively inherited ACTN2-myopathy has also been proposed in a single series., Methods: We provide clinical, imaging, and histological characterization of a series of patients with a novel biallelic ACTN2 variant., Results: We report seven patients from five families with a recurring biallelic variant in ACTN2: c.1516A>G (p.Arg506Gly), all manifesting with a consistent phenotype of asymmetric, progressive, proximal, and distal lower extremity predominant muscle weakness. None of the patients have cardiomyopathy or respiratory insufficiency. Notably, all patients report Palestinian ethnicity, suggesting a possible founder ACTN2 variant, which was confirmed through haplotype analysis in two families. Muscle biopsies reveal an underlying myopathic process with disruption of the intermyofibrillar architecture, Type I fiber predominance and atrophy. MRI of the lower extremities demonstrate a distinct pattern of asymmetric muscle involvement with selective involvement of the hamstrings and adductors in the thigh, and anterior tibial group and soleus in the lower leg. Using an in vitro splicing assay, we show that c.1516A>G ACTN2 does not impair normal splicing., Interpretation: This series further establishes ACTN2 as a muscle disease gene, now also including variants with a recessive inheritance mode, and expands the clinical spectrum of actinopathies to adult-onset progressive muscle disease., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Introduction: While the United States Preventative Services Task Force recommends osteoporosis screening for women 65 years and older, there is no definitive recommendation for routine osteoporosis screening in men. The purpose of this study was to determine the age at which the odds of fragility fractures (FFx) increase in men to help guide future policy discussions evaluating an optimal screening strategy in this population., Methods: Men older than 49 years were identified in the PearlDiver Patient Records Database. Patients were excluded if they had a prior fragility fracture, if they were at high risk for osteoporosis due to comorbidities, or if they carried a diagnosis of and/or were on treatment for osteoporosis. The prevalence of FFx was trended for each age group. A stratum-specific likelihood ratio (SSLR) analysis was conducted to identify data-driven strata that maximize the incremental FFx risk by age for men. Logistic regression analyses controlling for potential confounders were conducted to test these identified strata., Results: The incidence of FFx started to increase after the age of 64 years for men. Further, the identified data-driven age strata associated with a significant and incremental difference in fragility fractures were the following: 50-64, 65-69, 70-72, 73-75, 76-78, 79-80, and 81+. When compared to the youngest age stratum (50-64 years), multivariable regression showed the risk of fragility fracture incrementally increased starting in those aged 70-72 (RR, 1.31; 95% CI. 1.21-1.46; p < 0.001) with the highest risk in those aged 81+ (RR, 5.35; 95% CI, 5.10-5.62; p < 0.001)., Conclusion: In men without a pre-existing history of osteoporosis, the risk of fragility fractures starts to increase after the age of 70. Further work building upon these data may help to identify a specific age at which routine bone health screening in males can help to minimize fractures and their associated morbidity and mortality., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Background: Triage, the initial assessment and sorting of patients in the Emergency Department (ED), determines priority of evaluation and treatment. Little is known about the impact of undertriage, the underestimation of disease severity at triage, on clinical care in pediatric ED patients. We evaluate the impact of undertriage on time to disposition and treatment decisions in pediatric ED patients., Methods: This was a case control study of ED visits for patients <22 years of age, with an assigned Emergency Severity Index (ESI) score of 4 or 5, and associated hospital admission, nebulized treatment, supplemental oxygen, and/or intravenous (IV) line placement, between January 1, 2018, to June 30, 2022. Controls were sampled from a pool of patient visits with an ESI score of 3, matched by intervention, disposition, and date and hour of arrival. Primary outcome measures were time to order of intervention (nebulized treatment, oxygen administration, or IV placement) and time to disposition decision. A secondary outcome measure was return visits requiring admission or emergency intervention within 14 days of the index visit. Continuous variables (time to orders) were analyzed using Wilcoxon rank sum test and dichotomous outcomes (return visits) were compared using odds ratios with 95% confidence intervals. Analysis was performed with Python v3.10., Results: The final analysis included 7245 undertriaged patients. Undertriaged patients had longer times to orders for nebulized treatments, (p < 0.001) IV placement, (p < 0.001) and admission (p < 0.001) when compared to controls. There were no significant differences in time to supplemental oxygen delivery and time to discharge compared to controls. Undertriaged patients were more likely to experience a return visit requiring admission or emergency intervention (OR 3.74, 95% CI 3.32,4.22)., Conclusions: Undertriage in the pediatric ED is associated with delays in care and disposition decisions and increases likelihood of return visits., Competing Interests: Declaration of Competing Interest DB, JC, NM, CR, JC report no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

AMPA receptors are members of the glutamate receptor family and mediate a fast component of excitatory synaptic transmission at virtually all central synapses. Thus, their functional characteristics are a critical determinant of brain function. We evaluate intolerance of each GRIA gene to genetic variation using 3DMTR and report here the functional consequences of 52 missense variants in GRIA1-4 identified in patients with various neurological disorders. These variants produce changes in agonist EC 50 , response time course, desensitization, and/or receptor surface expression. We predict that these functional and localization changes will have important consequences for circuit function, and therefore likely contribute to the patients' clinical phenotype. We evaluated the sensitivity of variant receptors to AMPAR-selective modulators including FDA-approved drugs to explore potential targeted therapeutic options., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: With the increasing number of young patients undergoing primary total knee arthroplasty (TKA), there will be an increase in the number of patients who require revision. While the results of TKA in younger patients are well known, there is little information regarding to the outcomes of revision TKA in this population. The purpose of this study was to evaluate the clinical outcomes in patients <60 years of age undergoing aseptic revision TKA., Methods: We retrospectively reviewed 433 patients undergoing aseptic revision TKA between 2008 and 2019. There were 189 patients <60 years compared to a group of 244 patients >60 years undergoing revision TKA for aseptic failures in terms of implant survivorships, complications, and clinical outcomes. Patients were followed for a mean of 48 months (range, 24 to 149)., Results: A total of 28 (14.8%) patients less than 60 years of age required repeat revision compared to 25 (10.2%) 60 years or older (odds ratio (OR) 1.94, 95% confidence interval (CI) 0.73-5.22, P = .187). There were no differences regarding postprocedural Patient-Reported Outcomes Measurement Information System (PROMIS) physical health scores (72.3 ± 13.7 versus 72.0 ± 12.0, P = .66) and PROMIS mental health scores (66.6 ± 17.4 versus 65.8. ± 14.7, P = .72), at an average of 32.9 and 30.7 months, respectively. Postoperative infection occurred in 3 (1.6%) patients <60 years of age, while 12 (4.9%) postoperative infections occurred in patients 60 years or older (OR 0.75, 95% CI 0.06-10.2, P = .83)., Conclusion: There were no statistically significant differences in clinical outcomes between patients <60 versus > 60 years of age undergoing aseptic revision TKA., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Les dispensateurs de soins pédiatriques sont souvent le premier point de contact des enfants et des adolescents aux prises avec des problèmes de santé mentale, mais ils ne possèdent pas nécessairement les ressources (p. ex., l'accès à une équipe multidisciplinaire) ni la formation nécessaires pour procéder à leur dépistage ou à leur prise en charge. Le présent document de principes conjoint décrit les principaux rôles et les principales compétences à maîtriser pour évaluer et traiter les problèmes de santé mentale chez les enfants et les adolescents, de même que les facteurs qui optimisent le plus possible l'évolution de la santé mentale dans ces groupes d'âge. Il contient des conseils fondés sur des données probantes à propos du dépistage des préoccupations en matière de santé mentale chez les jeunes et leur famille ainsi qu'à propos des échanges sur le sujet. Les interventions préventives et thérapeutiques dont l'efficacité est démontrée en milieu communautaire sont abordées. Le présent document de principes, qui est fondamental, traite également des changements à l'enseignement de la médecine ainsi qu'aux systèmes et aux politiques de santé qui s'imposent pour améliorer la pratique clinique et les efforts de revendications au Canada, y compris les modèles de rémunération appropriés, les approches des soins abordées étape par étape, le financement gouvernemental ciblé, l'enseignement et la formation professionnelle., (© Société canadienne de pédiatrie 2023. Publié par Oxford University Press pour le compte de la Société canadienne de pédiatrie. Tous droits réservés. Pour obtenir une autorisation, écrivez à journals.permissions@oup.com.)

While paediatric care providers are often the first point of contact for children or youth experiencing mental health challenges, they may lack the resources (e.g., access to a multidisciplinary team) or training to adequately identify or manage such problems. This joint statement describes the key roles and competencies required to assess and address child and youth mental health problems, and the factors that optimize outcomes in this age group. Evidence-informed guidance on screening for and discussing mental health concerns with young people and families is provided. Preventive and therapeutic interventions with demonstrated efficacy in community care settings are discussed. This foundational statement also focuses on the changes to medical education, health systems, and health policy that are needed to improve clinical practice and advocacy efforts in Canada, including appropriate remuneration models, stepped-care approaches, targeted government funding, and professional training and education., Competing Interests: All authors: No reported conflicts of interest., (© Canadian Paediatric Society 2023. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

With improved treatment for human immunodeficiency virus (HIV), the demand for total knee arthroplasty (TKA) in this population has increased. Studying the relationship between HIV and postoperative complications following TKA will allow orthopaedic surgeons to accurately assess their patients' surgical risk and provide appropriate counseling. This study aims to understand how HIV impacts surgical and medical complications following TKA for osteoarthritis (OA). Patients identified in a national insurance database who underwent TKA for OA from 2010 to 2019 were divided into three cohorts: no HIV, asymptomatic HIV, and acquired immunodeficiency syndrome (AIDS). Univariate and multivariable regression analyses were performed to determine 90-day postoperative complications as well as 2-year surgical complications (revision surgery, prosthetic joint infection, aseptic loosening, and manipulation under anesthesia). A total of 855,373 patients were included, of whom 1,338 had asymptomatic HIV and 268 had AIDS. After multivariable regression analysis, patients with HIV had no difference in 2-year surgical complications relative to the control cohort. Within 90 days postoperatively, patients with asymptomatic HIV had increased odds of arrhythmia without atrial fibrillation and lower odds of anemia. Patients with AIDS had increased odds of anemia and renal failure. Patients with HIV and AIDS are at an increased risk for developing 90-day medical complications and 2-year surgical complications. However, after accounting for their comorbidities, the risk of 90-day complications was only mildly increased and the risk of 2-year surgical complications approximated the control cohort. Surgeons should pay particular attention to these patients' overall comorbidities, which appear to be more closely associated with postoperative risks than HIV status alone. Level of evidence: III., Competing Interests: G.J.G. reports royalty; payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, or educational events from Stryker, Inc. (formerly OrthoSensor); reports payment for expert testimony from Richie Hamlett, LLD for expert witness; reports support for attending meetings and/or travel from OrthoSensor, Inc.; reports leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid from Virginia Orthopaedic Society, American Association of Hip and Knee Surgeons; reports stock or stock options from OrthoSensor, Inc.S.C.T. reports leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid from AAHKS, AAOS. Rest authors declare no conflict of interest., (Thieme. All rights reserved.)

Chronic steroid and immunosuppressant use have been shown to increase the risk for postoperative complications in orthopedic surgery. Further understanding of the risks of immunosuppression is necessary to aid in risk stratification and patient counseling. However, these risks have not yet been explored in ankle fracture patients. Thus, the purpose of this study is to determine whether patients taking immunosuppressives are at an increased risk for morbidity and mortality following open reduction and internal fixation (ORIF) of ankle fractures. Patients undergoing operative treatment for ankle fractures from 2006 to 2018 were identified in the National Surgical Quality Improvement Program database. Patients were categorized based on their use of immunosuppressive medications. Postoperative outcomes assessed included superficial surgical site infections, deep surgical site infections, organ space infections, wound dehiscence, pneumonia, unplanned intubation, pulmonary embolism, urinary tract infection, renal failure, blood transfusion requirement, deep vein thrombosis, sepsis, cardiac arrest, extended length of hospital stay, readmission, reoperation, and mortality. Univariate and multivariate analyses were performed. In total, 10,331 patients underwent operative treatment for ankle fracture. Total 10,153 patients (98.3%) were not taking immunosuppressants and 178 (1.7%) were taking these medications. In multivariate analysis, patients taking immunosuppressants were at increased risk of pulmonary embolism (odds ratio [OR] 4.382; p = .041) and hospital readmission (OR 2.131; p = .021). Use of immunosuppressive medications is an independent risk factor for pulmonary embolism and readmission following ORIF for ankle fractures. Notably, no association with wound complications, infections, or sepsis was identified., (Copyright © 2023 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Literature regarding total knee arthroplasty (TKA) outcomes in sickle cell disease (SCD) is limited. Moreover, 10-year survivorship of SCD implants is unknown. This study aimed to observe 10-year cumulative incidence and indications for revision TKA in patients who did and did not have SCD., Methods: Patients who underwent primary TKA were identified using a large national database. The SCD patients were matched by age, sex, and a comorbidity index to a control cohort in a 1:4 ratio. The 10-year cumulative incidence rates were determined using Kaplan-Meier survival analyses. Multivariable analyses were conducted using Cox proportional hazard modeling. Chi-squared analyses were conducted to compare indications for revision between cohorts. In total, 1,010 SCD patients were identified, 100,000 patients included in the unmatched control, and 4,020 patients included in the matched control., Results: Compared to the unmatched control cohort, SCD patients exhibited higher 10-year all-cause revision (HR: 1.86; P < .001) with higher proportions of revisions for periprosthetic joint infection (PJI) (P < .001), aseptic loosening (P < .001), and hematoma (P < .001). Compared to the matched control, SCD patients had higher 10-year all-cause revision (Hazard Ratio (HR): 1.39; P = .034) with a higher proportion of revisions for PJI (P = .044), aseptic loosening (P = .003), and hematoma (P = .019)., Conclusion: Independent of other comorbidities, SCD patients are more likely to undergo revisions for PJI, aseptic loosening, and hematoma compared to patients who do not have SCD. Due to the high-risk of these complications, perioperative and postoperative surgical optimization should be enforced in SCD patients., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The study found that patients undergoing total knee arthroplasty with prior fragility fracture had increased risk of subsequent fragility fracture and periprosthetic fracture within 8 years postoperatively when compared to those without a prior history. However, these patients were not at increased risk for all-cause revision within this period., Purpose: The aim of this study was to characterize the association of prior FFs on long-term risk of secondary fragility fracture (FF), periprosthetic fracture (PPF), and revision TKA., Methods: Patients at least 50 years of age who underwent elective TKA were identified in the PearlDiver Database. Patients were stratified based on whether they sustained a FF within 3 years prior to TKA (7410 patients) or not (712,954 patients). Demographics and comorbidities were collected. Kaplan Meier analysis was used to observe the cumulative incidence of all-cause revision, PPF, and secondary FF within 8 years of TKA. Cox Proportional hazard ratio analysis was used to statistically compare the risk., Results: In total, 1.0% of patients had a FF within three years of TKA. Of these patients, only 22.6% and 10.9% had a coded diagnosis of osteoporosis and osteopenia, respectively, at time of TKA. The 8-year cumulative incidence of secondary FF and periprosthetic fracture was significantly higher in those with a prior FF (27.5% secondary FF and 1.9% PPF) when compared to those without (9.1% secondary FF and 0.7% PPF). After adjusting for covariates, patients with a recent FF had significantly higher risks of secondary FF (HR 2.73; p < 0.001) and periprosthetic fracture (HR 1.86; p < 0.001) than those without a recent FF., Conclusions: Recent FF before TKA is associated with increased risk for additional FF and PPF within 8 years following TKA. Surgeons should ensure appropriate management of fragility fracture is undertaken prior to TKA to minimize fracture risk, and if not, be vigilant to identify patients with prior FF or other bone health risk factors who may have undocumented osteoporosis., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Objective: FHL1-related reducing body myopathy is an ultra-rare, X-linked dominant myopathy. In this cross-sectional study, we characterize skeletal muscle ultrasound, muscle MRI, and cardiac MRI findings in FHL1-related reducing body myopathy patients., Methods: Seventeen patients (11 male, mean age 35.4, range 12-76 years) from nine independent families with FHL1-related reducing body myopathy underwent clinical evaluation, muscle ultrasound (n = 11/17), and lower extremity muscle MRI (n = 14/17), including Dixon MRI (n = 6/17). Muscle ultrasound echogenicity was graded using a modified Heckmatt scale. T1 and STIR axial images of the lower extremity muscles were evaluated for pattern and distribution of abnormalities. Quantitative analysis of intramuscular fat fraction was performed using the Dixon MRI images. Cardiac studies included electrocardiogram (n = 15/17), echocardiogram (n = 17/17), and cardiac MRI (n = 6/17). Cardiac muscle function, T1 maps, T2-weighted black blood images, and late gadolinium enhancement patterns were analyzed., Results: Muscle ultrasound showed a distinct pattern of increased echointensity in skeletal muscles with a nonuniform, multifocal, and "geographical" distribution, selectively involving the deeper fascicles of muscles such as biceps and tibialis anterior. Lower extremity muscle MRI showed relative sparing of gluteus maximus, rectus femoris, gracilis, and lateral gastrocnemius muscles and an asymmetric and multifocal, "geographical" pattern of T1 hyperintensity within affected muscles. Cardiac studies revealed mild and nonspecific abnormalities on electrocardiogram and echocardiogram with unremarkable cardiac MRI studies., Interpretation: Skeletal muscle ultrasound and muscle MRI reflect the multifocal aggregate formation in muscle in FHL1-related reducing body myopathy and are practical and informative tools that can aid in diagnosis and monitoring of disease progression., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Juvenile idiopathic arthritis (JIA) is a common pediatric rheumatic condition and is associated with symptoms such as joint pain that can negatively impact health-related quality of life. To effectively manage pain in JIA, young people, their families, and health care providers (HCPs) should be supported to discuss pain management options and make a shared decision. However, pain is often under-recognized, and pain management discussions are not optimal. No studies have explored decision-making needs for pain management in JIA using a shared decision making (SDM) model. We sought to explore families' decision-making needs with respect to pain management among young people with JIA, parents/caregivers, and HCPs., Methods: We conducted semi-structured virtual or face-to-face individual interviews with young people with JIA 8-18 years of age, parents/caregivers and HCPs using a qualitative descriptive study design. We recruited participants online across Canada and the United States, from a hospital and from a quality improvement network. We used interview guides based on the Ottawa Decision Support Framework to assess decision-making needs. We audiotaped, transcribed verbatim and analyzed interviews using thematic analysis., Results: A total of 12 young people (n = 6 children and n = 6 adolescents), 13 parents/caregivers and 11 HCPs participated in interviews. Pediatric HCPs were comprised of rheumatologists (n = 4), physical therapists (n = 3), rheumatology nurses (n = 2) and occupational therapists (n = 2). The following themes were identified: (1) need to assess pain in an accurate manner; (2) need to address pain in pediatric rheumatology consultations; (3) need for information on pain management options, especially nonpharmacological approaches; (4) importance of effectiveness, safety and ease of use of treatments; (5) need to discuss young people/families' values and preferences for pain management options; and the (6) need for decision support. Themes were similar for young people, parents/caregivers and HCPs, although their respective importance varied., Conclusions: Findings suggest a need for evidence-based information and communication about pain management options, which would be addressed by decision support interventions and HCP training in pain and SDM. Work is underway to develop such interventions and implement them into practice to improve pain management in JIA and in turn lead to better health outcomes., (© 2023. The Author(s).)