Inpatient or Outpatient: Does Initial Disposition Affect Outcomes in Trimalleolar Ankle Fractures?

Background The repair of trimalleolar fractures can be challenging for surgeons and may be managed as an inpatient or an outpatient. However, it is often unclear whether these patients should be admitted immediately or sent home from the emergency department (ED). This study aims to evaluate trimalleolar fractures treated surgically in the inpatient or outpatient settings to evaluate differences in outcomes for these patients. Methods A retrospective chart review of 223 patients undergoing open reduction internal fixation of a trimalleolar ankle fracture was performed from January 2015 to August 2022. Patients were classified by whether the fixation was performed as an inpatient or outpatient. Outcomes of interest included time from injury to surgery, complications, ED returns, and readmissions within 90 days. Results Inpatients had significantly higher ASA scores, BMI, and rates of comorbidities. Inpatient treatment was associated with faster time to surgery (median 2.0 vs. 9.0 days) and fewer delayed surgeries more than seven days from injury (18.4 vs. 67.9%). There were no differences in complications, 90-day ED returns, readmissions, or reoperation between groups. Conclusions Inpatient admission of patients presenting with trimalleolar ankle fractures resulted in faster time to surgery and fewer surgical delays than outpatient surgery. Despite having more preoperative risk factors, inpatients experienced similar postoperative outcomes as patients discharged home to return for outpatient surgery. Less restrictive admission criteria may improve the patient experience by providing more patients with support and pain control in the hospital setting while decreasing the time to surgery.

Exome copy number variant detection, analysis, and classification in a large cohort of families with undiagnosed rare genetic disease.

Copy number variants (CNVs) are significant contributors to the pathogenicity of rare genetic diseases and, with new innovative methods, can now reliably be identified from exome sequencing. Challenges still remain in accurate classification of CNV pathogenicity. CNV calling using GATK-gCNV was performed on exomes from a cohort of 6,633 families (15,759 individuals) with heterogeneous phenotypes and variable prior genetic testing collected at the Broad Institute Center for Mendelian Genomics of the Genomics Research to Elucidate the Genetics of Rare Diseases consortium and analyzed using the seqr platform. The addition of CNV detection to exome analysis identified causal CNVs for 171 families (2.6%). The estimated sizes of CNVs ranged from 293 bp to 80 Mb. The causal CNVs consisted of 140 deletions, 15 duplications, 3 suspected complex structural variants (SVs), 3 insertions, and 10 complex SVs, the latter two groups being identified by orthogonal confirmation methods. To classify CNV variant pathogenicity, we used the 2020 American College of Medical Genetics and Genomics/ClinGen CNV interpretation standards and developed additional criteria to evaluate allelic and functional data as well as variants on the X chromosome to further advance the framework. We interpreted 151 CNVs as likely pathogenic/pathogenic and 20 CNVs as high-interest variants of uncertain significance. Calling CNVs from existing exome data increases the diagnostic yield for individuals undiagnosed after standard testing approaches, providing a higher-resolution alternative to arrays at a fraction of the cost of genome sequencing. Our improvements to the classification approach advances the systematic framework to assess the pathogenicity of CNVs.

The landscape of regional missense mutational intolerance quantified from 125,748 exomes.

Missense variants can have a range of functional impacts depending on factors such as the specific amino acid substitution and location within the gene. To interpret their deleteriousness, studies have sought to identify regions within genes that are specifically intolerant of missense variation 1-12 . Here, we leverage the patterns of rare missense variation in 125,748 individuals in the Genome Aggregation Database (gnomAD) 13 against a null mutational model to identify transcripts that display regional differences in missense constraint. Missense-depleted regions are enriched for ClinVar 14 pathogenic variants, de novo missense variants from individuals with neurodevelopmental disorders (NDDs) 15,16 , and complex trait heritability. Following ClinGen calibration recommendations for the ACMG/AMP guidelines, we establish that regions with less than 20% of their expected missense variation achieve moderate support for pathogenicity. We create a missense deleteriousness metric (MPC) that incorporates regional constraint and outperforms other deleteriousness scores at stratifying case and control de novo missense variation, with a strong enrichment in NDDs. These results provide additional tools to aid in missense variant interpretation.

Considerations for reporting variants in novel candidate genes identified during clinical genomic testing.

Since the first novel gene discovery for a Mendelian condition was made via exome sequencing (ES), the rapid increase in the number of genes known to underlie Mendelian conditions coupled with the adoption of exome (and more recently, genome) sequencing by diagnostic testing labs has changed the landscape of genomic testing for rare disease. Specifically, many individuals suspected to have a Mendelian condition are now routinely offered clinical ES. This commonly results in a precise genetic diagnosis but frequently overlooks the identification of novel candidate genes. Such candidates are also less likely to be identified in the absence of large-scale gene discovery research programs. Accordingly, clinical laboratories have both the opportunity, and some might argue a responsibility, to contribute to novel gene discovery which should in turn increase the diagnostic yield for many conditions. However, clinical diagnostic laboratories must necessarily balance priorities for throughput, turnaround time, cost efficiency, clinician preferences, and regulatory constraints, and often do not have the infrastructure or resources to effectively participate in either clinical translational or basic genome science research efforts. For these and other reasons, many laboratories have historically refrained from broadly sharing potentially pathogenic variants in novel genes via networks like Matchmaker Exchange, much less reporting such results to ordering providers. Efforts to report such results are further complicated by a lack of guidelines for clinical reporting and interpretation of variants in novel candidate genes. Nevertheless, there are myriad benefits for many stakeholders, including patients/families, clinicians, researchers, if clinical laboratories systematically and routinely identify, share, and report novel candidate genes. To facilitate this change in practice, we developed criteria for triaging, sharing, and reporting novel candidate genes that are most likely to be promptly validated as underlying a Mendelian condition and translated to use in clinical settings.

Social vulnerability adversely affects emergency-department utilization but not patient-reported outcomes after total joint arthroplasty.

INTRODUCTION: Multiple studies demonstrate social deprivation is associated with inferior outcomes after total hip (THA) and total knee (TKA) arthroplasty; its effect on patient-reported outcomes is debated. The primary objective of this study evaluated the relationship between social vulnerability and the PROMIS-PF measure in patients undergoing THA and TKA. A secondary aim compared social vulnerability between patients who required increased resource utilization or experienced complications and those who didn't. MATERIALS AND METHODS: A retrospective review of 537 patients from March 2020 to February 2022 was performed. The Centers for Disease Control Social Vulnerability Index (SVI) were used to quantify socioeconomic disadvantage. The cohort was split into THA and TKA populations; univariate and multivariate analyses were performed to evaluate primary and secondary outcomes. Statistical significance was assessed at p < 0.05. RESULTS: 48.6% of patients achieved PROMIS-PF MCID at 1-year postoperatively. Higher levels of overall social vulnerability (0.40 vs. 0.28, p = 0.03) were observed in TKA patients returning to the ED within 90-days of discharge. Increased overall SVI (OR = 9.18, p = 0.027) and household characteristics SVI (OR = 9.57, p = 0.015) were independent risk factors for 90-day ED returns after TKA. In THA patients, increased vulnerability in the household type and transportation dimension was observed in patients requiring 90-day ED returns (0.51 vs. 0.37, p = 0.04). CONCLUSION: Despite an increased risk for 90-day ED returns, patients with increased social vulnerability still obtain good 1-year functional outcomes. Initiatives seeking to mitigate the effect of social deprivation on TJA outcomes should aim to provide safe alternatives to ED care during early recovery.

Inferring compound heterozygosity from large-scale exome sequencing data.

Recessive diseases arise when both copies of a gene are impacted by a damaging genetic variant. When a patient carries two potentially causal variants in a gene, accurate diagnosis requires determining that these variants occur on different copies of the chromosome (that is, are in trans) rather than on the same copy (that is, in cis). However, current approaches for determining phase, beyond parental testing, are limited in clinical settings. Here we developed a strategy for inferring phase for rare variant pairs within genes, leveraging genotypes observed in the Genome Aggregation Database (v2, n = 125,748 exomes). Our approach estimates phase with 96% accuracy, both in trio data and in patients with Mendelian conditions and presumed causal compound heterozygous variants. We provide a public resource of phasing estimates for coding variants and counts per gene of rare variants in trans that can aid interpretation of rare co-occurring variants in the context of recessive disease.

Non-White Race and Concomitant Orthopedic Conditions Are Risk Factors for Failure to Achieve Clinically Relevant Improvement After Total Knee Arthroplasty.

BACKGROUND: Data from the American Joint Replacement Registry demonstrate that 1-year minimal clinically important difference (MCID) achievement rates after total knee arthroplasty (TKA) are substantially lower when using general patient reported outcome measures, such as Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF), than joint specific measures. The purpose of this study was to evaluate patient characteristics and outcomes associated with MCID achievement after TKA using the PROMIS-PF measure. METHODS: A retrospective review of 263 patients undergoing TKA with preoperative and 1-year postoperative PROMIS-PF scores from March 12, 2020 to February 8, 2022 was performed. Three multivariate models were built to evaluate predictors of MCID achievement. Preoperative predictors evaluated included demographics, comorbidities, history of spine and knee surgery, and baseline PROMIS-PF. Postoperative clinical outcomes evaluated included lengths of stay, discharge statuses, complications, and utilizations of other orthopaedic services. RESULTS: There were 109 patients (41%) who achieved an MCID at 1-year postoperatively. Non-white patients had 2.17 times lower odds of achieving MCID. No clinical outcomes assessed were independently predictive of MCID achievement. During the 1-year postoperative period, 63% of patients sought care for another orthopaedic condition. Patients requiring postoperative injections on another joint had a 2.27 times lower odds of achieving MCID. Those seen for spine conditions postoperatively had a 2.44 lower odds of achieving MCID. CONCLUSIONS: Race, postoperative injections, and treatment for spine conditions after TKA were independent predictors of failure to achieve MCID. These results may guide preoperative patient consultation and risk-adjustment in future studies using PROMIS-PF as an endpoint for evaluation of TKA outcomes.

Effect of Lower Extremity Osteoarthritis on Outcomes of Lumbar Decompression.

BACKGROUND: The purpose of this study is to evaluate how hip or knee osteoarthritis (OA) and total joint arthroplasty impact the outcomes of patients undergoing lumbar decompression. METHODS: A retrospective review of 342 patients undergoing lumbar decompression without fusion from January 2019 and June 2021 at a single institution was performed. Univariate and multivariate analyses were used to compare outcomes between patients with and without concomitant hip or knee OA. RESULTS: Forty-six percent of patients had a hip or knee OA diagnosis and were higher risk as they were older, had higher BMIs, were more likely to be former smokers, had higher ASA scores, and were more likely to undergo 3+ level surgery. Postoperatively, after adjusting for differences between groups, hip or knee OA patients were more likely to be readmitted (OR=12.45, p=0.026) or have a complication (OR=13.77, p=0.031). However, patient reported outcomes as measured by Patient Reported Outcomes Measurement Information System-physical function. were similar at 1-3 months and 3-6 months. Higher levels of physical function were observed at 3-6 months postoperatively in hip OA patients with a history of THA. CONCLUSION: Patients with concomitant hip or knee OA are at higher risk for readmission and postoperative complications but may achieve similar levels of physical function as those without OA.

Exome copy number variant detection, analysis and classification in a large cohort of families with undiagnosed rare genetic disease.

Copy number variants (CNVs) are significant contributors to the pathogenicity of rare genetic diseases and with new innovative methods can now reliably be identified from exome sequencing. Challenges still remain in accurate classification of CNV pathogenicity. CNV calling using GATK-gCNV was performed on exomes from a cohort of 6,633 families (15,759 individuals) with heterogeneous phenotypes and variable prior genetic testing collected at the Broad Institute Center for Mendelian Genomics of the GREGoR consortium. Each family's CNV data was analyzed using the seqr platform and candidate CNVs classified using the 2020 ACMG/ClinGen CNV interpretation standards. We developed additional evidence criteria to address situations not covered by the current standards. The addition of CNV calling to exome analysis identified causal CNVs for 173 families (2.6%). The estimated sizes of CNVs ranged from 293 bp to 80 Mb with estimates that 44% would not have been detected by standard chromosomal microarrays. The causal CNVs consisted of 141 deletions, 15 duplications, 4 suspected complex structural variants (SVs), 3 insertions and 10 complex SVs, the latter two groups being identified by orthogonal validation methods. We interpreted 153 CNVs as likely pathogenic/pathogenic and 20 CNVs as high interest variants of uncertain significance. Calling CNVs from existing exome data increases the diagnostic yield for individuals undiagnosed after standard testing approaches, providing a higher resolution alternative to arrays at a fraction of the cost of genome sequencing. Our improvements to the classification approach advances the systematic framework to assess the pathogenicity of CNVs.

The Effect of Preoperative, Low-Dose Intrathecal Morphine on Patient Outcomes Following Lumbar Fusion Surgery: Can We Teach an Old Dog New Tricks?

BACKGROUND: Early pain control after lumbar fusion presents a challenge to patients and providers. Intrathecal morphine (ITM) has been used at the end of these procedures with limited benefit, but recent data suggest low-dose ITM at case initiation may be effective. This study aims to evaluate the use of preoperative ITM during lumbar fusion to determine whether there is a benefit for these patients. METHODS: One hundred and eighty lumbar fusion patients between 1 January 2018 and 31 May 2022 were evaluated. Patients were grouped by whether they received preoperative, low-dose ITM or not. Outcomes of interest included hospital narcotic consumption, pain scores, opioid-related complications, and complications within the first 90 days. RESULTS: Sixty-five study patients received 200 µg ITM at case initiation and 115 did not. No differences in length of stay, discharge disposition, or complications in the first 90 days were noted. ITM patients received fewer milligram morphine equivalents in the postanesthesia care unit (9.7 ± 31.23 vs 21.83 ± 21.07; P = 0.006) and on postoperative day 0 (18.60 ± 35.47 vs 35.47 ± 28.51; P = 0.001). Pain scores were lower in the ITM group both in the postanesthesia care unit and on postoperative day 0, with a decrease in extreme pain scores (>7; 35.4% vs 53.0%; P = 0.034). CONCLUSIONS: ITM appears to be safe and effective for reducing early pain and narcotic consumption on the day of surgery for lumbar fusion patients and may hold value for incorporation into rapid recovery protocols and for improving pain-related patient satisfaction. CLINICAL RELEVANCE: ITM appears to be safe and effective for reducing early pain and narcotic consumption on the day of surgery for lumbar fusion patients and may hold value for incorporation into rapid recovery protocols and for improving pain-related patient satisfaction.

Advanced variant classification framework reduces the false positive rate of predicted loss-of-function variants in population sequencing data.

Predicted loss of function (pLoF) variants are often highly deleterious and play an important role in disease biology, but many pLoF variants may not result in loss of function (LoF). Here we present a framework that advances interpretation of pLoF variants in research and clinical settings by considering three categories of LoF evasion: (1) predicted rescue by secondary sequence properties, (2) uncertain biological relevance, and (3) potential technical artifacts. We also provide recommendations on adjustments to ACMG/AMP guidelines' PVS1 criterion. Applying this framework to all high-confidence pLoF variants in 22 genes associated with autosomal-recessive disease from the Genome Aggregation Database (gnomAD v.2.1.1) revealed predicted LoF evasion or potential artifacts in 27.3% (304/1,113) of variants. The major reasons were location in the last exon, in a homopolymer repeat, in a low proportion expressed across transcripts (pext) scored region, or the presence of cryptic in-frame splice rescues. Variants predicted to evade LoF or to be potential artifacts were enriched for ClinVar benign variants. PVS1 was downgraded in 99.4% (162/163) of pLoF variants predicted as likely not LoF/not LoF, with 17.2% (28/163) downgraded as a result of our framework, adding to previous guidelines. Variant pathogenicity was affected (mostly from likely pathogenic to VUS) in 20 (71.4%) of these 28 variants. This framework guides assessment of pLoF variants beyond standard annotation pipelines and substantially reduces false positive rates, which is key to ensure accurate LoF variant prediction in both a research and clinical setting.

Absorbable Sutures and Telemedicine for Patients Undergoing Trigger Finger Release.

Background In the setting of the COVID-19 pandemic, the development of care processes that reduce the need for in-person clinic visits while maintaining low complication rates is needed. The purpose of this study is to assess the outcomes of patients undergoing trigger finger release with various suture and follow-up visit types to assess the feasibility of shifting towards telemedicine-based follow-up protocols. Methods A retrospective review of 329 patients undergoing trigger finger release was performed. Patients were classified based on whether or not they received in-office follow-ups; whether they received absorbable or non-absorbable sutures; and whether they were treated using a telemedicine and absorbable suture protocol or other combination of sutures and follow-ups. Univariate statistics were performed to compare outcomes between groups. Results Patients who did not undergo in-office follow-up were more likely to experience residual stiffness or contracture (11.4% vs. 4.1%; p=0.033) but had no significant differences in 30-day reoperation, emergency department (ED) returns, wound complaints, and Quick DASH (Disabilities of the Arm, Shoulder, and Hand) scores. When comparing chromic absorbable sutures to non-absorbable sutures, those with absorbable sutures were significantly more likely to have telemedicine visits but were also more likely to have wound complaints (17.9% vs. 8.5%; p=0.022). There was no significant difference in two- and six-week pain scores, 30-day reoperation, ED returns, residual symptoms, and Quick DASH scores. When comparing patients treated using the absorbable suture and telemedicine protocol with those receiving any other type of suture and postoperative follow-up, no significant differences in any postoperative clinical outcome measures were observed. Conclusion The results of this study demonstrate that the use of an absorbable suture and telemedicine protocol for patients undergoing trigger finger release yields similar outcomes as traditional methods of care. However, the use of absorbable sutures may result in decreased patient satisfaction with surgical wound healing.

Transosseous Fixation of the Distal Tibiofibular Syndesmosis: Comparison of Interosseous Suture and Endobutton Across Age Groups.

Background In the ankle, suture bridge fixation for syndesmotic injuries is commonly employed. Initial recommendations for suture bridge constructs advised against using the device in patients with insufficient quantity or quality of bone. Therefore, many surgeons limit its use to younger, more athletic patients and use traditional screw fixation in older, less active patients. The purpose of this study is to compare the outcomes of suture bridge fixation for syndesmotic repair in patients ≥ 60 years old vs patients < 60 years old. Methods A retrospective review of 140 ankle fracture patients from a single institution who received suture bridge fixation between July 13, 2010, and February 2, 2022, was performed. Patient data was obtained from patient records in the electronic health record. Univariate analysis, including chi-square and independent t-tests, was used. Complications included delayed wound healing, infection, hardware loosening, and non-union. Results There were no significant differences in demographics, comorbidities, primary or other procedures, loss of fixation, and neuropathy between groups. There was also no difference within the distribution of the mechanism of injury, affected side, or Weber classification. Finally, the rate of complication and complication type showed no significant differences between patients 60 years and older versus 60 years and younger. Complication rates and types in patients > 60 years versus < 60 years were not significantly different. Conclusion The use of the suture bridge fixation in patients > 60 years may not lead to an increased risk of complications and appears to be safe for use.

Phenotype and genetic analysis of data collected within the first year of NeuroDev.

Genetic association studies have made significant contributions to our understanding of the etiology of neurodevelopmental disorders (NDDs). However, these studies rarely focused on the African continent. The NeuroDev Project aims to address this diversity gap through detailed phenotypic and genetic characterization of children with NDDs from Kenya and South Africa. We present results from NeuroDev's first year of data collection, including phenotype data from 206 cases and clinical genetic analyses of 99 parent-child trios. Most cases met criteria for global developmental delay/intellectual disability (GDD/ID, 80.3%). Approximately half of the children with GDD/ID also met criteria for autism. Analysis of exome-sequencing data identified a pathogenic or likely pathogenic variant in 13 (17%) of the 75 cases from South Africa and 9 (38%) of the 24 cases from Kenya. Data from the trio pilot are publicly available, and the NeuroDev Project will continue to develop resources for the global genetics community.

Are We Considering the Whole Patient? The Impact of Physical and Mental Health on the Outcomes of Spine Care.

STUDY DESIGN: Retrospective, observational. OBJECTIVE: To evaluate the influence of baseline health status on the physical and mental health (MH) outcomes of spine patients. SUMMARY OF BACKGROUND DATA: Spine conditions can have a significant burden on both the physical and MH of patients. To date, few studies have evaluated the outcomes of both dimensions of health, particularly in nonoperative populations. MATERIALS AND METHODS: At their first visit to a multidisciplinary spine clinic, 2668 nonoperative patients completed the Patient-reported Outcomes Measurement Information System-Global Health (PROMIS-GH) instrument and a questionnaire evaluating symptoms and goals of care. Patients were stratified by their baseline percentile score of the MH and physical health (PH) components of the PROMIS-GH. Four groups of patients were compared based on the presence or absence of bottom quartile PH or MH scores. The primary end point was the achievement of a minimal clinically important difference (MCID) on the MH or PH components at follow-up. Multivariate regression assessed the predictors of MCID achievement. RESULTS: After controlling for demographics, symptoms, and goals, each 1-point increase in baseline PROMIS-GH mental score reduced the odds of achieving MH MCID by 9.0% ( P <0.001). Conversely, each 1-point increase in baseline GH-physical score increased the odds of achieving MCID by 4.5% ( P =0.005). Each 1-point increase in baseline GH-physical score reduced the odds of achieving PH MCID by 12.5% ( P <0.001), whereas each 1-point increase in baseline GH-mental score increased the odds of achieving MCID by 5.0% ( P <0.001). CONCLUSIONS: Spine patients presenting with the lowest levels of physical or MH were most likely to experience clinically significant improvement in those domains. However, lower levels of physical or mental health made it less likely that patients would experience significant improvement in the alternative domain. Physicians should evaluate and address the complex spine population holistically to maximize improvement in both physical and mental health status.

Adductor Canal Blocks Are Not Associated With Improved Early Postoperative Outcomes in Patients Undergoing Total Knee Arthroplasty.

Background: As length of stay after total knee arthroplasty (TKA) continues to shorten, interventions that may reduce early postoperative pain and complications must be studied. Peripheral nerve block is being explored as a potential means of improving pain management. The purpose of this study was to evaluate the impact of adductor canal block (ACB) on postoperative outcomes for patients undergoing TKA. Methods: We conducted a retrospective review of 565 patients who received unilateral TKA under spinal anesthesia with a periarticular anesthetic injection. Patients were divided by ACB status. Univariate comparisons and multivariate regression were used to compare outcomes for patients receiving ACBs vs those who did not. Results: Of the 565 patients, 167 received an ACB, and 398 did not. Patients who received an ACB were less likely to require nausea medication during the immediate postoperative period. Length of stay, narcotic consumption, rate of discharge to home, postanesthesia care unit recovery time, urinary retention, ability to complete physical therapy, and 30-day readmission rate did not differ significantly between groups. After risk adjustment, the only significant finding was decreased likelihood of nausea in patients receiving an ACB. Conclusion: ACBs appear to have little to no significant impact on early clinical outcomes in patients having TKA under spinal anesthesia with a periarticular anesthetic injection. Further study of larger patient cohorts is required to validate these findings.

Inferring compound heterozygosity from large-scale exome sequencing data.

Recessive diseases arise when both the maternal and the paternal copies of a gene are impacted by a damaging genetic variant in the affected individual. When a patient carries two different potentially causal variants in a gene for a given disorder, accurate diagnosis requires determining that these two variants occur on different copies of the chromosome (i.e., are in trans) rather than on the same copy (i.e. in cis). However, current approaches for determining phase, beyond parental testing, are limited in clinical settings. We developed a strategy for inferring phase for rare variant pairs within genes, leveraging genotypes observed in exome sequencing data from the Genome Aggregation Database (gnomAD v2, n=125,748). When applied to trio data where phase can be determined by transmission, our approach estimates phase with 95.7% accuracy and remains accurate even for very rare variants (allele frequency < 1×10-4). We also correctly phase 95.9% of variant pairs in a set of 293 patients with Mendelian conditions carrying presumed causal compound heterozygous variants. We provide a public resource of phasing estimates from gnomAD, including phasing estimates for coding variants across the genome and counts per gene of rare variants in trans, that can aid interpretation of rare co-occurring variants in the context of recessive disease.

Advanced variant classification framework reduces the false positive rate of predicted loss of function (pLoF) variants in population sequencing data.

Predicted loss of function (pLoF) variants are highly deleterious and play an important role in disease biology, but many of these variants may not actually result in loss-of-function. Here we present a framework that advances interpretation of pLoF variants in research and clinical settings by considering three categories of LoF evasion: (1) predicted rescue by secondary sequence properties, (2) uncertain biological relevance, and (3) potential technical artifacts. We also provide recommendations on adjustments to ACMG/AMP guidelines's PVS1 criterion. Applying this framework to all high-confidence pLoF variants in 22 autosomal recessive disease-genes from the Genome Aggregation Database (gnomAD, v2.1.1) revealed predicted LoF evasion or potential artifacts in 27.3% (304/1,113) of variants. The major reasons were location in the last exon, in a homopolymer repeat, in low per-base expression (pext) score regions, or the presence of cryptic splice rescues. Variants predicted to be potential artifacts or to evade LoF were enriched for ClinVar benign variants. PVS1 was downgraded in 99.4% (162/163) of LoF evading variants assessed, with 17.2% (28/163) downgraded as a result of our framework, adding to previous guidelines. Variant pathogenicity was affected (mostly from likely pathogenic to VUS) in 20 (71.4%) of these 28 variants. This framework guides assessment of pLoF variants beyond standard annotation pipelines, and substantially reduces false positive rates, which is key to ensure accurate LoF variant prediction in both a research and clinical setting.

Acetabular Total Hip Arthroplasty Revision: A Summary of Operative Factors, Outcomes, and Comparison of Approaches.

BACKGROUND: Revision total hip arthroplasty (THA) presents a greater risk to patients than primary THA, and surgical approach may impact outcomes. This study aimed to summarize acetabular revisions at our institution and to compare outcomes between direct anterior and posterior revision THA. METHODS: A series of 379 acetabular revision THAs performed from January 2010 through August 2022 was retrospectively reviewed. Preoperative, perioperative, and postoperative factors were summarized for all revisions and compared between direct anterior and posterior revision THA. RESULTS: The average time to acetabular revision THA was 10 years (range, 0.04 to 44.1), with mechanical failure (36.7%) and metallosis (25.6%) being the most prevalent reasons for revision. No differences in age, body mass index, or sex were noted between groups. Anterior revision patients had a significantly shorter length of stay (2.2 versus 3.2 days, P = .003) and rate of discharge to a skilled nursing facility (7.5 versus 25.2%, P = .008). In the 90-day postoperative period, 9.2% of patients returned to the emergency department (n = 35) and twelve patients (3.2%) experienced a dislocation. There were 13.2% (n = 50) of patients having a rerevision during the follow-up period with a significant difference between anterior and posterior approaches (3.8 versus 14.7%, respectively, P = .049). CONCLUSION: This study provides some evidence that the anterior approach may be protective against skilled nursing facility discharge and rerevision and contributes to decreased lengths of stay. We recommend surgeons select the surgical approach for revision THA based on clinical preferences and patient factors.

The Efficacy of Telemedicine Versus In-Person Education for High-Risk Patients Undergoing Primary Total Joint Arthroplasty.

BACKGROUND: While multiple studies have demonstrated the positive impact of preoperative education on total joint arthroplasty (TJA) outcomes, the traditional method of conducting in-person individualized counseling or group education may limit access to these resources for a subset of the population. This study aimed to evaluate the use of preoperative telemedicine and in-person educational programs for primary TJA patients to determine if the utilization of telemedicine is inferior to in-person education in high-risk populations. METHODS: A retrospective chart review of all "high-risk" patients undergoing primary unilateral TKA or THA by 1 of 10 board-certified surgeons at a single institution over 1 year was performed. Patients were prospectively classified as high-risk based on race/ethnicity, comorbidities, and socioeconomic and psychosocial factors. Demographics, comorbidities, and hospital outcomes were compared between patients receiving preoperative nurse navigator education via telemedicine versus those receiving face-to-face education. RESULTS: When comparing the interventions, telemedicine education was noninferior to face-to-face visits. No significant differences between postoperative length of stay, discharge home, 30-day emergency department return, or 30-day readmission rates were noted. Within the telemedicine group, patients who received video consultations were found to be 6 times more likely to be discharged home after surgery (odds ratio (OR): 5.95, 95% confidence interval (CI): 2.00 to 25.49; P = .004) and less likely to have a 30-day readmission than the phone consultations (OR: 0.36, 95% CI: 0.12 to 0.94: P = .050). CONCLUSION: This study demonstrates that telemedicine is not inferior to in-person preoperative education for patients undergoing unilateral TJA, although video-based consultation may improve outcomes over phone-only education.