The learning curve for robotic-assisted total hip arthroplasty in low, medium, and high-volume surgeons.

Background: Robotic systems have been designed to increase the accuracy of implant alignment in total knee and hip arthroplasty. This technology is associated with a learning curve for the operative time to reach peak efficiency in its use. Prior studies done on high-volume orthopedic surgeons have suggested a learning curve of 14-35 cases for robotic-assisted total hip arthroplasty (THA). It is unclear if this learning curve is different for surgeons with lower volumes. Methods: Data was collected retrospectively from 299 THA procedures done by three different surgeons, with low (1-15 cases/year), medium (16-50), and high (51+) volume caseload. The learning curve was assessed primarily by average operative time from cases 1-20, 21-50, and 51+. Results: The high-volume surgeon had a learning curve of 20 cases, while the low and medium volume surgeons had no significant decrease in their operative time through the cases included in the study (20 and 63, respectively). Conclusions: High volume surgeons have a learning curve of about 20 cases, while low and medium volume surgeons have a longer curve, which was not able to be measured in this study.

Do social media use and patient satisfaction scores correlate with online award recognition among hip and knee arthroplasty specialists?

INTRODUCTION: The physician-patient interaction now begins before patients arrive in the office. Online ratings, social media profiles, and online award status are all components of physician online reputation which contributes to the patient's initial impressions. Therefore, it is important to understand the interplay of these factors and determine if there is a consistent trend indicating the value of this information. METHODS: We Identified all (N â€‹= â€‹160) registered American Association of Hip and Knee Surgeons (AAHKS) in New England using the https://findadoctor.aahks.net/tool for Massachusetts (MA), Connecticut (CT), Rhode Island (RI), Vermont (VT), New Hampshire (NH), and Maine (ME) on 6/26/2023. We collected surgeon age, fellowship graduation year, and practice type (i.e. Academic or Private). The average 5-star rating and number of ratings were collected from four websites. Any professional-use Facebook, Instagram, Twitter, LinkedIn, YouTube Channel, Personal Websites, or Institutional Websites were identified and a modified SMI Score was calculated. Finally, Castle Connolly Top Doctor, Local Magazine (e.g. Boston Magazine) Top Doctor, or the presence of having any award was noted for each surgeon. RESULTS: We identified several significant trends indicating that online awards were associated with higher online ratings. Social media presence, as determined by SMI Score, was also correlated with higher ratings overall and a higher likelihood of having an online award. CONCLUSION: Given the observed trends and reported importance patients place on ratings and awards, surgeons may consider increasing online engagement via social media and encouraging patients to share their experience via online ratings.

The Relative Importance of Factors That Applicants Weigh When Ranking Adult Reconstruction Fellowships as Well as Their Perspectives on Robotic-Assisted Arthroplasty.

BACKGROUND: Orthopedic Surgery Fellowship programs offer highly specialized training that varies based on the training environment and surgical experience. Additionally, for Adult Reconstruction programs, robotic-assisted surgery exposure has been a widely discussed topic. The purpose of this study was to determine the relative value of various factors to Adult Hip and Knee Fellowship applicants, and their perceptions of robotic-assisted arthroplasty. METHODS: We surveyed 780 applicants who applied to our fellowship to matriculate in 2020 to 2024. We received 158 responses (20.3% response rate). We assessed factors concerning people and perceptions, logistics, salary and benefits, program reputation and curriculum, and surgical experience. Additionally, we surveyed fellows' attitudes toward using robotic surgery and its impact on patient outcomes. RESULTS: The highest-rated factors were Level of Hands-On Operative Experience (4.83), Revision Hip Volume (4.72), Revision Knee Volume (4.71), Multiple Surgical Exposures to the Hip (4.59), and Clinical Case Variety (4.59). Respondents who were postfellowship matriculation placed significantly more value on Exposure to Multiple Attendings with Surgical Diversity (P = .01), and Anterior Hip Volume (P = .04), and less value on Geographic Location (P = .04) and Patient-Specific Instrumentation (P = .02) than prematriculates. Overall, 65% of applicants plan to or currently use robotics, 7.6% do not, and 27.2% said "Maybe". Those who plan to or currently use robotics most cited procedure fidelity, patient-preference, and marketability as reasons to use robotics. CONCLUSIONS: Hands-on surgical experience and revision volume were the most important factors for fellowship applicants. Applicants placed lower importance on robotics exposure and their perspectives on robotics in their future practice were highly variable. Our results will inform fellowship programs and future applicants what previous applicants have valued in their training to help guide fellowship program structure, resource management, as well as recruitment.

Product warranties by orthopaedic surgery companies. Quality control or a new fad?

Introduction: Product guarantees are known to the manufacturing industry, however warranties have been rare in Orthopaedic surgery. Over the last 10 years, select manufacturers of implants have instituted warranties of varying scope, length, and reimbursement. This phenomenon prompted us to investigate the landscape of warranties in Orthopaedics and compare that to other medical industries to better inform their impact on patient care. Methods: We conducted a systematic review of patient access material of over 120 Orthopaedic manufacturers including that of the Top 25 grossing companies of 2022 to identify the prevalence and scope of these warranties. Results: We identified eight companies that offer a warranty on implants. The expiration time for the implant warranties ranged from one year to lifetime. The scope of the warranties ranged from coverage of a one-time component replacement to outcome-based guarantees that cover any complications and revisions that may result from the surgery. Discussion: While the use of warranties remains uncommon in orthopaedics, their utility is expanding and evolving. Contemporary warranties appear to have a focus on enhancing product-marketability and improving quality-control.

Clinical validity assessment of genes frequently tested on intellectual disability/autism sequencing panels.

PURPOSE: Neurodevelopmental disorders (NDDs), such as intellectual disability (ID) and autism spectrum disorder (ASD), exhibit genetic and phenotypic heterogeneity, making them difficult to differentiate without a molecular diagnosis. The Clinical Genome Resource Intellectual Disability/Autism Gene Curation Expert Panel (GCEP) uses systematic curation to distinguish ID/ASD genes that are appropriate for clinical testing (ie, with substantial evidence supporting their relationship to disease) from those that are not. METHODS: Using the Clinical Genome Resource gene-disease validity curation framework, the ID/Autism GCEP classified genes frequently included on clinical ID/ASD testing panels as Definitive, Strong, Moderate, Limited, Disputed, Refuted, or No Known Disease Relationship. RESULTS: As of September 2021, 156 gene-disease pairs have been evaluated. Although most (75%) were determined to have definitive roles in NDDs, 22 (14%) genes evaluated had either Limited or Disputed evidence. Such genes are currently not recommended for use in clinical testing owing to the limited ability to assess the effect of identified variants. CONCLUSION: Our understanding of gene-disease relationships evolves over time; new relationships are discovered and previously-held conclusions may be questioned. Without periodic re-examination, inaccurate gene-disease claims may be perpetuated. The ID/Autism GCEP will continue to evaluate these claims to improve diagnosis and clinical care for NDDs.

TMPRSS3 Gene Variants With Implications for Auditory Treatment and Counseling.

Objective: To identify and report novel variants in the TMPRSS3 gene and their clinical manifestations related to hearing loss as well as intervention outcomes. This information will be helpful for genetic counseling and treatment planning for these patients. Methods: Literature review of previously reported TMPRSS3 variants was conducted. Reported variants and associated clinical information was compiled. Additionally, cohort data from 18 patients, and their families, with a positive result for TMPRSS3-associated hearing loss were analyzed. Genetic testing included sequencing and copy number variation (CNV) analysis of TMPRSS3 and the Laboratory for Molecular Medicine's OtoGenome-v1, -v2, or -v3 panels. Clinical data regarding patient hearing rehabilitation was interpreted along with their genetic testing results and in the context of previously reported cochlear implant outcomes in individuals with TMPRSS3 variants. Results: There have been 87 previously reported TMPRSS3 variants associated with non-syndromic hearing loss in more than 20 ancestral groups worldwide. Here we report occurrences of known variants as well as one novel variant: deletion of Exons 1-5 and 13 identified from our cohort of 18 patients. The hearing impairment in many of these families was consistent with that of previously reported patients with TMPRSS3 variants (i.e., typical down-sloping audiogram). Four patients from our cohort underwent cochlear implantation. Conclusion: Bi-allelic variants of TMPRSS3 are associated with down-sloping hearing loss regardless of ancestry. The outcome following cochlear implantation in patients with variants of TMPRSS3 is excellent. Therefore, cochlear implantation is strongly recommended for hearing rehabilitation in these patients.

Disease-specific ACMG/AMP guidelines improve sequence variant interpretation for hearing loss.

PURPOSE: The ClinGen Variant Curation Expert Panels (VCEPs) provide disease-specific rules for accurate variant interpretation. Using the hearing loss-specific American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines, the Hearing Loss VCEP (HL VCEP) illustrates the utility of expert specifications in variant interpretation. METHODS: A total of 157 variants across nine HL genes, previously submitted to ClinVar, were curated by the HL VCEP. The curation process involved collecting published and unpublished data for each variant by biocurators, followed by bimonthly meetings of an expert curation subgroup that reviewed all evidence and applied the HL-specific ACMG/AMP guidelines to reach a final classification. RESULTS: Before expert curation, 75% (117/157) of variants had single or multiple variants of uncertain significance (VUS) submissions (17/157) or had conflicting interpretations in ClinVar (100/157). After applying the HL-specific ACMG/AMP guidelines, 24% (4/17) of VUS and 69% (69/100) of discordant variants were resolved into benign (B), likely benign (LB), likely pathogenic (LP), or pathogenic (P). Overall, 70% (109/157) variants had unambiguous classifications (B, LB, LP, P). We quantify the contribution of the HL-specified ACMG/AMP codes to variant classification. CONCLUSION: Expert specification and application of the HL-specific ACMG/AMP guidelines effectively resolved discordant interpretations in ClinVar. This study highlights the utility of ClinGen VCEPs in supporting more consistent clinical variant interpretation.

Consensus interpretation of the p.Met34Thr and p.Val37Ile variants in GJB2 by the ClinGen Hearing Loss Expert Panel.

PURPOSE: Pathogenic variants in GJB2 are the most common cause of autosomal recessive sensorineural hearing loss. The classification of c.101T>C/p.Met34Thr and c.109G>A/p.Val37Ile in GJB2 are controversial. Therefore, an expert consensus is required for the interpretation of these two variants. METHODS: The ClinGen Hearing Loss Expert Panel collected published data and shared unpublished information from contributing laboratories and clinics regarding the two variants. Functional, computational, allelic, and segregation data were also obtained. Case-control statistical analyses were performed. RESULTS: The panel reviewed the synthesized information, and classified the p.Met34Thr and p.Val37Ile variants utilizing professional variant interpretation guidelines and professional judgment. We found that p.Met34Thr and p.Val37Ile are significantly overrepresented in hearing loss patients, compared with population controls. Individuals homozygous or compound heterozygous for p.Met34Thr or p.Val37Ile typically manifest mild to moderate hearing loss. Several other types of evidence also support pathogenic roles for these two variants. CONCLUSION: Resolving controversies in variant classification requires coordinated effort among a panel of international multi-institutional experts to share data, standardize classification guidelines, review evidence, and reach a consensus. We concluded that p.Met34Thr and p.Val37Ile variants in GJB2 are pathogenic for autosomal recessive nonsyndromic hearing loss with variable expressivity and incomplete penetrance.

Correction: ClinGen expert clinical validity curation of 164 hearing loss gene-disease pairs.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

ClinGen expert clinical validity curation of 164 hearing loss gene-disease pairs.

PURPOSE: Proper interpretation of genomic variants is critical to successful medical decision making based on genetic testing results. A fundamental prerequisite to accurate variant interpretation is the clear understanding of the clinical validity of gene-disease relationships. The Clinical Genome Resource (ClinGen) has developed a semiquantitative framework to assign clinical validity to gene-disease relationships. METHODS: The ClinGen Hearing Loss Gene Curation Expert Panel (HL GCEP) uses this framework to perform evidence-based curations of genes present on testing panels from 17 clinical laboratories in the Genetic Testing Registry. The HL GCEP curated and reviewed 142 genes and 164 gene-disease pairs, including 105 nonsyndromic and 59 syndromic forms of hearing loss. RESULTS: The final outcome included 82 Definitive (50%), 12 Strong (7%), 25 Moderate (15%), 32 Limited (20%), 10 Disputed (6%), and 3 Refuted (2%) classifications. The summary of each curation is date stamped with the HL GCEP approval, is live, and will be kept up-to-date on the ClinGen website ( https://search.clinicalgenome.org/kb/gene-validity ). CONCLUSION: This gene curation approach serves to optimize the clinical sensitivity of genetic testing while reducing the rate of uncertain or ambiguous test results caused by the interrogation of genes with insufficient evidence of a disease link.

Death by Suicide-The EMS Profession Compared to the General Public.

BACKGROUND: In 2016, nearly 45,000 deaths in the United States were attributed to suicide making this the 10th leading cause of death for all ages. National survey data suggest that among Emergency Medical Technicians (EMTs), including firefighters and Paramedics, rates of suicide are significantly higher than among the general public. EMTs face high levels of acute and chronic stress as well as high rates of depression and substance abuse, which increase their risk of suicide. OBJECTIVE/AIM: To determine the statewide Mortality Odds Ratio (MOR) of suicide completion among EMTs as compared to non-EMTs in Arizona. METHODS: We analyzed the Arizona Vital Statistics Information Management System Electronic Death Registry of all adult (≥18) deaths between January 1, 2009 and December 31, 2015. Manual review of decedent occupation was performed to identify the EMT cohort; all other deaths were included in the non-EMT cohort. Using the underlying cause of death as the outcome, we calculated the MOR of both the EMT and non-EMT cohorts. RESULTS: There were a total of 350,998 deaths during the study period with 7,838 categorized as suicide. The proportion of deaths attributed to suicide among EMTs was 5.2% (63 of 1,205 total deaths) while the percentage among non-EMTs was 2.2% (7,775/349,793) (p < 0.0001). The crude Mortality Odds Ratio for EMTs compared with non-EMTs was [cMOR 2.43; 95% CI (1.88-3.13)]. After adjusting for gender, age, race, and ethnicity, EMTs had higher odds that their death was by suicide than non-EMTs [aMOR: 1.39; 95% CI (1.06-1.82)]. CONCLUSION: In this statewide analysis, we found that EMTs had a significantly higher Mortality Odds Ratio due to suicide compared to non-EMTs. Further research is necessary to identify the underlying causes of suicide among EMTs and to develop effective prevention strategies.

The ClinGen Epilepsy Gene Curation Expert Panel-Bridging the divide between clinical domain knowledge and formal gene curation criteria.

The field of epilepsy genetics is advancing rapidly and epilepsy is emerging as a frequent indication for diagnostic genetic testing. Within the larger ClinGen framework, the ClinGen Epilepsy Gene Curation Expert Panel is tasked with connecting two increasingly separate fields: the domain of traditional clinical epileptology, with its own established language and classification criteria, and the rapidly evolving area of diagnostic genetic testing that adheres to formal criteria for gene and variant curation. We identify critical components unique to the epilepsy gene curation effort, including: (a) precise phenotype definitions within existing disease and phenotype ontologies; (b) consideration of when epilepsy should be curated as a distinct disease entity; (c) strategies for gene selection; and (d) emerging rules for evaluating functional models for seizure disorders. Given that de novo variants play a prominent role in many of the epilepsies, sufficient genetic evidence is often awarded early in the curation process. Therefore, the emphasis of gene curation is frequently shifted toward an iterative precuration process to better capture phenotypic associations. We demonstrate that within the spectrum of neurodevelopmental disorders, gene curation for epilepsy-associated genes is feasible and suggest epilepsy-specific conventions, laying the groundwork for a curation process of all major epilepsy-associated genes.

Assessing the gene-disease association of 19 genes with the RASopathies using the ClinGen gene curation framework.

The RASopathies are a complex group of conditions regarding phenotype and genetic etiology. The ClinGen RASopathy Expert Panel (RAS EP) assessed published and other publicly available evidence supporting the association of 19 genes with RASopathy conditions. Using the semiquantitative literature curation method developed by the ClinGen Gene Curation Working Group, evidence for each gene was curated and scored for Noonan syndrome (NS), Costello syndrome, cardiofaciocutaneous syndrome, NS with multiple lentigines, and Noonan-like syndrome with loose anagen hair. The curated evidence supporting each gene-disease relationship was then discussed and approved by the ClinGen RASopathy Expert Panel. Each association's strength was classified as definitive, strong, moderate, limited, disputed, or no evidence. Eleven genes were classified as definitively associated with at least one RASopathy condition. Two genes classified as strong for association with at least one RASopathy condition while one gene was moderate and three were limited. The RAS EP also disputed the association of two genes for all RASopathy conditions. Overall, our results provide a greater understanding of the different gene-disease relationships within the RASopathies and can help in guiding and directing clinicians, patients, and researchers who are identifying variants in individuals with a suspected RASopathy.

Expert specification of the ACMG/AMP variant interpretation guidelines for genetic hearing loss.

Due to the high genetic heterogeneity of hearing loss (HL), current clinical testing includes sequencing large numbers of genes, which often yields a significant number of novel variants. Therefore, the standardization of variant interpretation is crucial to provide consistent and accurate diagnoses. The Hearing Loss Variant Curation Expert Panel was created within the Clinical Genome Resource to provide expert guidance for standardized genomic interpretation in the context of HL. As one of its major tasks, our Expert Panel has adapted the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines for the interpretation of sequence variants in HL genes. Here, we provide a comprehensive illustration of the newly specified ACMG/AMP HL rules. Three rules remained unchanged, four rules were removed, and the remaining 21 rules were specified. These rules were further validated and refined using a pilot set of 51 variants assessed by curators and disease experts. Of the 51 variants evaluated in the pilot, 37% (19/51) changed category based upon application of the expert panel specified rules and/or aggregation of evidence across laboratories. These HL-specific ACMG/AMP rules will help standardize variant interpretation, ultimately leading to better care for individuals with HL.

Curating Clinically Relevant Transcripts for the Interpretation of Sequence Variants.

Variant interpretation depends on accurate annotations using biologically relevant transcripts. We have developed a systematic strategy for designating primary transcripts and have applied it to 109 hearing loss-associated genes that were divided into three categories. Category 1 genes (n = 38) had a single transcript; category 2 genes (n = 33) had multiple transcripts, but a single transcript was sufficient to represent all exons; and category 3 genes (n = 38) had multiple transcripts with unique exons. Transcripts were curated with respect to gene expression reported in the literature and the Genotype-Tissue Expression Project. In addition, high-frequency loss-of-function variants in the Genome Aggregation Database and disease-causing variants in ClinVar and the Human Gene Mutation Database across the 109 genes were queried. These data were used to classify exons as clinically significant, insignificant, or of uncertain significance. Interestingly, 6% of all exons, containing 124 reportedly disease-causing variants, were of uncertain significance. Finally, we used exon-level next-generation sequencing quality metrics generated at two clinical laboratories and identified a total of 43 technically challenging exons in 20 different genes that had inadequate coverage and/or homology issues that might lead to false-variant calls. We have demonstrated that transcript analysis plays a critical role in accurate clinical variant interpretation.

Reclassification of the BRAF p.Ile208Val variant by case-level data sharing.

The ClinVar database is a useful tool for patients and physicians to view variant interpretations submitted by clinical and nonclinical labs. However, variants of uncertain significance (VUS) in ClinVar can pose a significant burden on patients. If possible, it is important to resolve discrepancies and uncertainties surrounding interpreted variants. Here we highlight a case of a family who received a report of a variant (c.622A>G, p.Ile208Val) in BRAF following prenatal RASopathy testing. The variant had been previously classified by our laboratory as a VUS, so the mother contacted our laboratory via ClinVar for further information, which prompted reevaluation of the variant. Multiple sources of case-level data as well as the presence of the variant in the general population yielded sufficient evidence to reclassify the variant as likely benign. This reclassification alleviated significant concern for the family, and the child was born healthy with no clinical manifestations of Noonan syndrome or a RASopathy.