T cells instruct myeloid cells to produce inflammasome-independent IL-1ß and cause autoimmunity.

The cytokine interleukin (IL)-1ß is a key mediator of antimicrobial immunity as well as autoimmune inflammation. Production of IL-1ß requires transcription by innate immune receptor signaling and maturational cleavage by inflammasomes. Whether this mechanism applies to IL-1ß production seen in T cell-driven autoimmune diseases remains unclear. Here, we describe an inflammasome-independent pathway of IL-1ß production that was triggered upon cognate interactions between effector CD4+ T cells and mononuclear phagocytes (MPs). The cytokine TNF produced by activated CD4+ T cells engaged its receptor TNFR on MPs, leading to pro-IL-1ß synthesis. Membrane-bound FasL, expressed by CD4+ T cells, activated death receptor Fas signaling in MPs, resulting in caspase-8-dependent pro-IL-1ß cleavage. The T cell-instructed IL-1ß resulted in systemic inflammation, whereas absence of TNFR or Fas signaling protected mice from CD4+ T cell-driven autoimmunity. The TNFR-Fas-caspase-8-dependent pathway provides a mechanistic explanation for IL-1ß production and its consequences in CD4+ T cell-driven autoimmune pathology.

The future of liver transplantation.

Over the last 50 years, liver transplantation has evolved into a procedure routinely performed in many countries worldwide. Those able to access this therapy frequently experience a miraculous risk-benefit ratio, particularly if they face the imminently life-threatening disease. Over the decades, the success of liver transplantation, with dramatic improvements in early posttransplant survival, has aggressively driven demand. However, despite the emergence of living donors to augment deceased donors as a source of organs, supply has lagged far behind demand. As a result, rationing has been an unfortunate focus in recent decades. Recent shifts in the epidemiology of liver disease combined with transformative innovations in liver preservation suggest that the underlying premise of organ shortage may erode in the foreseeable future. The focus will sharpen on improving equitable access while mitigating constraints related to workforce training, infrastructure for organ recovery and rehabilitation, and their associated costs. Research efforts in liver preservation will undoubtedly blossom with the aim of optimizing both the timing and conditions of transplantation. Coupled with advances in genetic engineering, regenerative biology, and cellular therapies, the portfolio of innovation, both broad and deep, offers the promise that, in the future, liver transplantation will not only be broadly available to those in need but also represent a highly durable life-saving therapy.

Disparities in Tuberculosis Incidence by Race and Ethnicity Among the U.S.-Born Population in the United States, 2011 to 2021 : An Analysis of National Disease Registry Data.

BACKGROUND: Elevated tuberculosis (TB) incidence rates have recently been reported for racial/ethnic minority populations in the United States. Tracking such disparities is important for assessing progress toward national health equity goals and implementing change. OBJECTIVE: To quantify trends in racial/ethnic disparities in TB incidence among U.S.-born persons. DESIGN: Time-series analysis of national TB registry data for 2011 to 2021. SETTING: United States. PARTICIPANTS: U.S.-born persons stratified by race/ethnicity. MEASUREMENTS: TB incidence rates, incidence rate differences, and incidence rate ratios compared with non-Hispanic White persons; excess TB cases (calculated from incidence rate differences); and the index of disparity. Analyses were stratified by sex and by attribution of TB disease to recent transmission and were adjusted for age, year, and state of residence. RESULTS: In analyses of TB incidence rates for each racial/ethnic population compared with non-Hispanic White persons, incidence rate ratios were as high as 14.2 (95% CI, 13.0 to 15.5) among American Indian or Alaska Native (AI/AN) females. Relative disparities were greater for females, younger persons, and TB attributed to recent transmission. Absolute disparities were greater for males. Excess TB cases in 2011 to 2021 represented 69% (CI, 66% to 71%) and 62% (CI, 60% to 64%) of total cases for females and males, respectively. No evidence was found to indicate that incidence rate ratios decreased over time, and most relative disparity measures showed small, statistically nonsignificant increases. LIMITATION: Analyses assumed complete TB case diagnosis and self-report of race/ethnicity and were not adjusted for medical comorbidities or social determinants of health. CONCLUSION: There are persistent disparities in TB incidence by race/ethnicity. Relative disparities were greater for AI/AN persons, females, and younger persons, and absolute disparities were greater for males. Eliminating these disparities could reduce overall TB incidence by more than 60% among the U.S.-born population. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Physiological determinants of mechanical efficiency during advanced ageing and disuse.

This study aimed to determine which physiological factors impact net efficiency (ηnet) in oldest-old individuals at different stages of skeletal muscle disuse. To this aim, we examined ηnet, central haemodynamics, peripheral circulation, and peripheral factors (skeletal muscle fibre type, capillarization and concentration of mitochondrial DNA [mtDNA]). Twelve young (YG; 25 ± 2 years), 12 oldest-old mobile (OM; 87 ± 3 years), and 12 oldest-old immobile (OI; 88 ± 4 years) subjects performed dynamic knee extensor (KE) and elbow flexors (EF) exercise. Pulmonary oxygen uptake, photoplethysmography, Doppler ultrasound and muscle biopsies of the vastus lateralis and biceps brachii were used to assess central and peripheral adaptations to advanced ageing and disuse. Compared to the YG (12.1 ± 2.4%), the ηnet of lower-limb muscle was higher in the OM (17.6 ± 3.5%, P < 0.001), and lower in the OI (8.9 ± 1.9%, P < 0.001). These changes in ηnet during KE were coupled with significant peripheral adaptations, revealing strong correlations between ηnet and the proportion of type I muscle fibres (r = 0.82), as well as [mtDNA] (r = 0.77). No differences in ηnet were evident in the upper-limb muscles between YG, OM and OI. In view of the differences in limb-specific activity across the lifespan, these findings suggest that ηnet is reduced by skeletal muscle inactivity and not by chronological age, per se. Likewise, this study revealed that the age-related changes in ηnet are not a consequence of central or peripheral haemodynamic adaptations, but are likely a product of peripheral changes related to skeletal muscle fibre type and mitochondrial density. KEY POINTS: Although the effects of ageing and muscle disuse deeply impact the cardiovascular and skeletal muscle function, the combination of these factors on the mechanical efficiency are still a matter of debate. By measuring both upper- and lower-limb muscle function, which experience differing levels of disuse, we examined the influence of central and peripheral haemodynamics, and skeletal muscle factors linked to mechanical efficiency. Across the ages and degree of disuse, upper-limb muscles exhibited a preserved work economy. In the legs the oldest-old without mobility limitations exhibited an augmented mechanical efficiency, which was reduced in those with an impairment in ambulation. These changes in mechanical efficiency were associated with the proportion of type I muscle fibres. Recognition that the mechanical efficiency is not simply age-dependent, but the consequence of inactivity and subsequent skeletal muscle changes, highlights the importance of maintaining physical activity across the lifespan.

Comparative analysis of CRISPR off-target discovery tools following ex vivo editing of CD34+ hematopoietic stem and progenitor cells.

While a number of methods exist to investigate CRISPR off-target (OT) editing, few have been compared head-to-head in primary cells after clinically relevant editing processes. Therefore, we compared in silico tools (COSMID, CCTop, and Cas-OFFinder) and empirical methods (CHANGE-Seq, CIRCLE-Seq, DISCOVER-Seq, GUIDE-Seq, and SITE-Seq) after ex vivo hematopoietic stem and progenitor cell (HSPC) editing. We performed editing using 11 different gRNAs complexed with Cas9 protein (high-fidelity [HiFi] or wild-type versions), then performed targeted next-generation sequencing of nominated OT sites identified by in silico and empirical methods. We identified an average of less than one OT site per guide RNA (gRNA) and all OT sites generated using HiFi Cas9 and a 20-nt gRNA were identified by all OT detection methods with the exception of SITE-seq. This resulted in high sensitivity for the majority of OT nomination tools and COSMID, DISCOVER-Seq, and GUIDE-Seq attained the highest positive predictive value (PPV). We found that empirical methods did not identify OT sites that were not also identified by bioinformatic methods. This study supports that refined bioinformatic algorithms could be developed that maintain both high sensitivity and PPV, thereby enabling more efficient identification of potential OT sites without compromising a thorough examination for any given gRNA.

Increased Alpha Angles and Younger Age Increase the Risk of Contralateral Femoral Acetabular Impingement Syndrome Symptom Development and Surgical Intervention: A Systematic Review.

PURPOSE: To identify the preoperative risk factors associated with contralateral symptom development and surgical intervention for patients presenting with unilateral femoral acetabular impingement (FAI) syndrome. METHODS: A literature search was performed using PubMed and Scopus computerized databases according to the 2020 Preferred Reporting Items for Systematic Meta-Analyses guidelines. Studies evaluating preoperative risk factors associated with the contralateral progression of FAI were included. Quality assessment was completed using the Methodological Index for Non-Randomized Studies criteria. RESULTS: A total of 5 studies (n = 1,011 patients; mean age, 29.9 years) published from 2013 to 2022 met the inclusion/exclusion criteria. Mean follow-up ranged from 12 to 132 months. The overall rate of contralateral progression of symptomatic FAI ranged from 32.4% to 81%. Increased alpha angle was frequently reported factor associated with contralateral symptom progression, followed by decreased total arc of rotation, decreased internal rotation, reduced neck-shaft angle, and head-neck offset. The incidence rate of progression to contralateral surgery ranged from 15.7% to 24% of patients. Younger age was frequently reported factor associated with contralateral surgical intervention, followed by male sex, increased level of activity, and increased alpha angle. CONCLUSIONS: Increased alpha angle and younger age were commonly reported risk factors associated with an increased risk of symptom development and surgical progression of contralateral FAI, respectively. The overall rate of contralateral progression of symptomatic FAI and the rate of progression to surgical intervention ranged up to 81% and 24%, respectively. This information may help both patients and surgeons to establish expectations regarding development of contralateral hip symptoms and possible need for surgery. LEVEL OF EVIDENCE: Level III; systematic review of Level II-III studies.

ChatGPT-3.5 Responses Require Advanced Readability for the General Population and May Not Effectively Supplement Patient-Related Information Provided by the Treating Surgeon Regarding Common Questions About Rotator Cuff Repair.

PURPOSE: To investigate the accuracy of ChatGPT's responses to frequently asked questions prior to rotator cuff repair surgery. METHODS: The 10 most common frequently asked questions related to rotator cuff repair were compiled from 4 institution websites. Questions were then input into ChatGPT-3.5 in 1 session. The provided ChatGPT-3.5 responses were analyzed by 2 orthopaedic surgeons for reliability, quality, and readability using the Journal of the American Medical Association Benchmark criteria, the DISCERN score, and the Flesch-Kincaid Grade Level. RESULTS: The Journal of the American Medical Association Benchmark criteria score was 0, indicating the absence of reliable source material citations. The mean Flesch-Kincaid Grade Level was 13.4 (range, 11.2-15.0). The mean DISCERN score was 43.4 (range, 36-51), indicating that the quality of the responses overall was considered fair. All responses cited making final decision-making to be made with the treating physician. CONCLUSIONS: ChatGPT-3.5 provided substandard patient-related information in alignment with recommendations from the treating surgeon regarding common questions around rotator cuff repair surgery. Additionally, the responses lacked reliable source material citations, and the readability of the responses was relatively advanced with a complex language style. CLINICAL RELEVANCE: The findings of this study suggest that ChatGPT-3.5 may not effectively supplement patient-related information in the context of recommendations provided by the treating surgeon prior to rotator cuff repair surgery.

All-Inside and Inside-Out Repair Techniques for Bucket-Handle Meniscus Tears Both Result in Improved Patient Outcomes and a Broad Range of Failure Rates: A Systematic Review.

PURPOSE: To compare patient-reported outcomes, failure rates, risk factors for failure, and complications in patients with bucket-handle meniscus tears (BHMTs) undergoing repair with inside-out (IO) versus all-inside (AI) techniques. METHODS: A literature search was performed using the PubMed, Embase, and Scopus databases from database inception to August 2023 according to the 2020 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. The inclusion criteria consisted of Level I to IV clinical studies published in the past 10 years with greater than 2 years of follow-up that evaluated patient-reported outcome scores and/or the incidence of failure after IO or AI repairs for BHMTs. Clinical studies not reporting outcomes or failure rates, older studies using outdated implants, animal studies, reviews, letters to the editor, case reports, cadaveric studies, and articles not written in the English language or with English-language translation were excluded. Study quality was assessed using the Methodological Index for Non-randomized Studies (MINORS) criteria. Outcomes were reported as ranges and qualitatively compared. RESULTS: A total of 16 studies published from 2013 to 2023, consisting of 1,062 patients with BHMTs, were identified. Thirteen studies (14 cohorts, 649 patients) reported on AI repair (mean age range, 23.7-32 years) and 7 studies (7 cohorts, 413 patients) reported on IO repair (mean age range, 16.7-34.6 years). Both groups had improved postoperative Lysholm and Tegner scores. Decreased range of motion was the most commonly reported complication in the AI group (range, 2.6%-4%), whereas adhesions for arthrofibrosis were the most commonly reported complication in the IO group (n = 12; range, 6%-7.9%). The overall reported failure rate ranged from 6.9% to 20.5% within the AI group and from 0% to 20% within the IO group. CONCLUSIONS: AI and IO repair techniques for BHMTs both result in improved Lysholm and Tegner scores. However, broad ranges of failure are reported in the literature, with overall failure rates ranging from 6.9% to 20.5% after AI repair and from 0% to 20% after IO repair. Younger age and isolated medial BHMT repair are the most frequently reported risk factors for the AI technique, whereas postoperative stiffness is the most frequently reported complication after both repair techniques. LEVEL OF EVIDENCE: Level IV, systematic review of Level I to IV studies.

Ulnar Collateral Ligament Reconstruction Is Commonly Performed Using a Palmaris Graft and Provides Favorable Patient Outcomes With Variable Return-to-Play and Postoperative Complication Rates: A Systematic Review.

PURPOSE: To systematically review the literature to provide an updated evaluation of postoperative clinical outcomes, return to play (RTP), and postoperative complications after primary ulnar collateral ligament reconstruction (UCLR) in throwing and nonthrowing athletes at minimum 2-year follow-up. METHODS: A literature search was performed on November 25, 2023, by querying the Embase, PubMed, and Scopus online databases using the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The inclusion criteria consisted of Level I to IV human clinical studies reporting postoperative outcomes and/or complications after primary UCLR with minimum 2-year follow-up. The exclusion criteria consisted of non-English-language studies; biomechanical, animal, and cadaveric studies; review articles; letters to the editor; and studies not reporting postoperative outcomes or complications. Study quality was evaluated using the Methodological Index for Non-Randomized Studies criteria. The incidence of reported complications among the included studies was extracted. Clinical outcome scores included the Kerlan-Jobe Orthopaedic Clinic Shoulder & Elbow (KJOC) score, Andrews-Timmerman (AT) score, and satisfaction score. RTP data were also extracted. RESULTS: A total of 21 studies published from 2006 to 2023, consisting of 2,452 patients (2,420 male patients) with a mean age of 21.7 years (mean range, 12-65 years) and mean follow-up period of 50.5 months (mean range, 24-151.2 months), were included. The mean Methodological Index for Non-Randomized Studies score was 16 (range, 13-20). A total of 46% of patients (1,138 of 2,452) underwent concomitant ulnar nerve transposition. Palmaris graft was the most frequently used method (66.6%; n = 1,799), followed by hamstring graft (26.0%, n = 703). At the final follow-up, mean postoperative KJOC scores ranged from 72.0 to 88.0; mean AT scores, from 83.6 to 98.3; and mean satisfaction scores, from 86.1 to 98.3. The overall RTP rate ranged from 62.5% to 100% at a mean range of 9.5 to 18.5 months. The total incidence of complications ranged from 0% to 31.8%, with 0% to 7.4% of patients undergoing revision surgery. CONCLUSIONS: UCLR was commonly performed using a palmaris graft, with concomitant ulnar nerve transposition reported in 46% of patients. At a mean follow-up of 50.5 months, mean postoperative KJOC scores ranged from 72 to 98.3, AT scores ranged from 83.6 to 98.3, and satisfaction scores ranged from 86.1 to 98.3, with variable RTP rates. LEVEL OF EVIDENCE: Level IV, systematic review of Level II to IV studies.

Reported Anterior Cruciate Ligament Injury Incidence in Adolescent Athletes Is Greatest in Female Soccer Players and Athletes Participating in Club Sports: A Systematic Review and Meta-analysis.

PURPOSE: To identify the risk of anterior cruciate ligament (ACL) injury in adolescent athletes based on sex, sport, and sport affiliation. METHODS: A literature search was performed using 3 online databases (PubMed, Cochrane Library, and EMBASE) from database inception to November 2023 per the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included studies consisted of Level I or II studies reporting on ACL injury exposures in time (hours) or injuries per 1,000 athlete-exposures (AEs) (1 game or practice) in adolescent athletes. Exclusion criteria consisted of non-English studies, case reports, animal/cadaveric studies, and review articles. Methodological quality and bias assessment of the included studies was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. ACL injuries were analyzed and pooled to calculate incidence rates (IRs), per-season risk, and relative risk (RR) based on sex, sport, and sport affiliation (club sport participation vs school sport participation). RESULTS: A total of 1,389 ACL injuries over 19,134,167 AEs were identified (IR, 0.075; 95% confidence interval [CI], 0.071-0.079). Of these, 670 ACL injuries were reported in female athletes over 7,549,892 AEs (IR, 0.089; 95% CI, 0.087-0.091) with 719 in males over 11,584,275 AEs (IR, 0.062; 95% CI, 0.058-0.067). The greatest RR for ACL injury in females was in soccer (RR, 3.12; 95% CI, 2.58-3.77) for AEs. The greatest per-season risk of ACL injuries reported in female athletes occurred in soccer (1.08%), basketball (1.03%), and gymnastics (1.01%). The greatest per-season risk of ACL injuries reported in male athletes occurred in football (0.82%), lacrosse (0.64%), and soccer (0.35%). Club sport participation, in both AEs (RR, 3.94; 95% CI, 3.19-4.87) and hours of exposure (RR, 1.57; 95% CI, 1.07-2.28), demonstrated an increased risk of ACL injury. CONCLUSIONS: The risk of ACL injuries was 1.56-fold greater in adolescent female athletes compared with male athletes. The highest-risk sport for females was soccer. Participation in club sports possessed higher rates of injury compared with school sports. LEVEL OF EVIDENCE: Level II; meta-analysis of Level I and II studies.

Massive Irreparable Rotator Cuff Tears Treated With a Tuberoplasty Yield Favorable Clinical Outcomes With Variable Rates of Complications: A Systematic Review.

PURPOSE: To systematically review the patient-reported outcomes and postoperative complications following tuberoplasty for the treatment of massive irreparable rotator cuff tears. METHODS: A literature search was conducted using PubMed and EMBASE computerized databases from database inception to June 2023 in accordance with the 2020 Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Included studies evaluated clinical outcomes, postoperative complications, and reoperation rates following tuberoplasty for the treatment of massive irreparable rotator cuff tears. Exclusion criteria consisted of non-English language, cadaveric studies, case reports, animal studies, studies with overlapping cohorts, letters to editors, and review articles. Study quality was assessed using the Methodological Index for Non-Randomized Studies criteria. Clinical outcome scores included the visual analog scale for pain, University of California Los Angeles score, and Constant score. RESULTS: Seven studies from 2002 to 2023 consisting of 123 patients with a mean age of 66.5 years (mean range, 63-70.4 years) were included. The mean follow-up time ranged from 18 to 98 months. The mean Methodological Index for Non-Randomized Studies score was 13.5 (range, 13-15). At final follow-up, the mean postoperative visual analog scale pain scores ranged from 2.3 to 2.5, University of California-Los Angeles shoulder score from 27.2 to 27.7, and Constant scores from 59.2 to 90.6. Postoperative active forward flexion and abduction ranged from 131° to 165°, and 123° to 160°, respectively. The change in acromiohumeral distance postoperatively ranged from -1 mm to -0.6 mm. The rate of postoperative complications ranged from 0% to 19% of patients, while 0% to 19% of patients underwent revision surgery to reverse shoulder arthroplasty. CONCLUSIONS: Tuberoplasty for the treatment of massive irreparable rotator cuff tears results in good clinical outcomes with significant pain relief in select populations. However, the variable reoperation rates should be considered when counseling patients. LEVEL OF EVIDENCE: Level IV, systematic review of Level IV studies.

The Sex or Race of Program Directors May Not Play a Significant Role in Impacting Diversity Among Orthopaedic Surgery Residents.

PURPOSE: To identify the influence of residency program characteristics, including the presence of under-represented minorities in medicine (URiM) and/or female program directors (PDs), on the race and sex distribution of orthopaedic surgery residency trainees. METHODS: All active and Accreditation Council for Graduate Medical Education-accredited orthopaedic surgery residency programs from 2017-2021 that reported usable information in the Residency Explorer Tool were included. Data collected included program characteristics, as well as faculty and resident sex distribution, ethnicity, race, and demographic characteristics. The PDs' specific sex, ethnicity, race, and demographic characteristics were collected using residency program websites. The prevalence of factors in programs with the top quartile of female and URiM residents was compared with that in programs with the bottom 3 quartiles. RESULTS: Data were obtained from 148 of 200 Accreditation Council for Graduate Medical Education-accredited programs (3,694 residents). The 52 excluded programs had no usable information in the Residency Explorer Tool or on an identifiable program website. Overall, 15.9% of residents in orthopaedic surgery residency programs were women and 14% were under-represented minorities. The rates of female PDs and chairs were 12.4% and 6.9%, respectively, whereas those of URiM PDs and chairs were 8.3% and 4.6%, respectively. Programs with more female residents were not associated with female PDs (P = .79) or URiM PDs (P = .48). Programs with a greater percentage of URiM residents were not associated with URiM PDs (P = .16). Larger programs (P = .021) and university-based programs (P = .048) had a greater percentage of female residents. Orthopaedic residency programs with visa sponsorship had a greater percentage of URiM residents (P = .017). CONCLUSIONS: Programs with a higher percentage of female or URiM residents did not show a significant association with having female or URiM PDs. Larger programs and university-affiliated programs were more likely to have a larger percentage of female residents, whereas programs that offered visa sponsorship had a higher percentage of URiM residents. CLINICAL RELEVANCE: This study highlights factors influencing diversity among orthopaedic surgery residents. Although the presence of female or URiM PDs does not influence the percentage of female or URiM residents, other program characteristics such as size, affiliation, and visa sponsorship offer potentially actionable insights for promoting greater diversity in orthopaedic training. Doing so may increase under-represented groups within the field and could ultimately impact patient care and improve health care equity.

Isolated Primary Latarjet Procedures for Anterior Shoulder Instability Results in High Rates of Graft Resorption and Glenohumeral Degenerative Changes With Low Rates of Failure at a Minimum 2-Year Follow-Up: A Systematic Review.

PURPOSE: To evaluate the incidence of postoperative complications after an isolated primary Latarjet procedure for anterior shoulder instability at a minimum 2-year follow-up. METHODS: A systematic review was performed in accordance with 2020 PRISMA guidelines. EMBASE, Scopus, and PubMed databases were queried from database inception through September 2022. The literature search was limited to human clinical studies reporting on postoperative complications and adverse events after a primary Latarjet procedure with a minimum 2-year follow-up. Risk of bias was measured using the Newcastle-Ottawa Scale. RESULTS: Twenty-two studies, consisting of 1,797 patients (n = 1,816 shoulders), with a mean age of 24 years were identified. The overall postoperative complication rate ranged from 0% to 25.7%, with the most common complication being persistent shoulder pain (range: 0%-25.7%). Radiological changes included graft resorption (range: 7.5%-100%) and glenohumeral degenerative changes (range: 0%-52.5%). Recurrent instability following surgery was documented in 0% to 35% of shoulders, while the incidence of bone block fractures ranged from 0% to 6% of cases. Postoperative nonunion, infection, and hematomas had a reported incidence rate ranging from 0% to 16.7%, 0% to 2.6%, and 0% to 4.4%, respectively. Overall, 0% to 7.5% of surgeries were reported failures, and 0% to 11.1% of shoulders required reoperation, with a revision rate ranging from 0% to 7.7%. CONCLUSIONS: The incidence of complications following the primary Latarjet procedure for shoulder instability was variable, ranging from 0% to 25.7%. High rates of graft resorption, degenerative changes, and nonunion were present while failure and revision rates remained low at a minimum 2-year follow-up. LEVEL OF EVIDENCE: Level III, systematic review of Level I-III studies.

Platelet-Rich Plasma, Bone Marrow Aspirate Concentrate, and Hyaluronic Acid Injections Outperform Corticosteroids in Pain and Function Scores at a Minimum of 6 Months as Intra-Articular Injections for Knee Osteoarthritis: A Systematic Review and Network Meta-analysis.

PURPOSE: To compare the efficacy of common intra-articular injections used in the treatment of knee osteoarthritis, including corticosteroid (CS), hyaluronic acid (HA), platelet-rich plasma (PRP), and bone marrow aspirate concentrate (BMAC), with a minimum follow-up of 6-months. METHODS: A literature search was conducted using the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in August 2022 in the following databases: PubMed/MEDLINE, Scopus, Cochrane Database of Controlled Trials, and the Cochrane Database of Systematic Reviews. Level I to II randomized clinical trials with a minimum follow-up of 6 months that investigated the treatments of interest were included. Patient-reported outcome scores for pain and function at baseline and at latest follow-up were extracted, and the change in scores was converted to uniform 0 to 100 scales. Arm-based Bayesian network meta-analysis using a random-effects model was created to compare the treatment arms in pain and function. RESULTS: Forty-eight studies comprising a total of 9,338 knees were included. The most studied intra-articular injection was HA (40.9%), followed by placebo (26.2%), PRP (21.5%), CS (8.8%), and then BMAC (2.5%). HA and PRP both led to a significant improvement in pain compared with placebo. HA, PRP, and BMAC all led to a significant improvement in function scores when compared with placebo. Surface under the cumulative ranking curves (SUCRAs) of the interventions revealed that PRP, BMAC, and HA were the treatments with the highest likelihood of improvement in both pain and function, with overall SUCRA scores of 91.54, 76.46, and 53.12, respectively. The overall SUCRA scores for CS and placebo were 15.18 and 13.70, respectively. CONCLUSIONS: At a minimum 6-month follow-up, PRP demonstrated significantly improved pain and function for patients with knee osteoarthritis compared with placebo. Additionally, PRP exhibited the highest SUCRA values for these outcomes when compared with BMAC, HA, and CS. LEVEL OF EVIDENCE: Level II, meta-analysis of Level I to II studies.

Meniscus Extrusion, Radial Tears, and Root Tears.

Management of meniscal radial and root tears and extrusion is complex and has changed significantly over recent years. It is important to provide a comprehensive overview of the management of radial and root tears and meniscal extrusion and be aware of the currently available evidence on repair techniques, rehabilitation, and outcomes following radial and root repairs.

Social Media Use and Patient Ratings in Shoulder and Elbow Surgeons: How Many 'Likes' for Five Stars?

INTRODUCTION: Social media plays an important role in healthcare and physician selection by facilitating direct communication with patients and impacting physician ratings. A concern however is the increased online scrutiny and negative impact on patient satisfaction with these connections. This study aimed to investigate whether social media activity by fellowship-trained shoulder and elbow surgeons impacts patient's perceptions and ratings on physician rating websites (PRWs). MATERIALS AND METHODS: The American Shoulder and Elbow Surgeons (ASES) physician directory was used to identify currently practicing shoulder and elbow surgeons in the US. Physician ratings were collected from Healthgrades, Google reviews, and Vitals. The surgeons were divided into two groups: social media users (SMU) and non-social media users (NSMU). The association of social media use with online physician ratings was evaluated using simple and multilinear regressions. RESULTS: A total of 385 ASES surgeons were included and 21.3% were SMU. SMU were younger (mean age, 48 years) compared to NSMU (mean age, 51 years) (p = 0.01), all other demographics were comparable including sex (p = 0.797), medical degree (MD or DO) (p = 0.114), and geographic location within the US (p = 0.49). SMU had significantly higher ratings on Healthgrades (p<0.001) and Vitals (p<0.001). However, social media use did not impact the total number of ratings on PRWs. Additionally, surgeons who utilized Facebook had higher physician ratings and number of website reviews on Healthgrades (p = 0.028 and p=0.014, respectively). In addition, surgeons who used Twitter had higher ratings on Healthgrades (p<0.001) and Vitals (p=0.001). Surgeons with a greater average number of likes per post on Twitter had significantly higher average ratings across all three sites (p=0.004). Surgeons with a greater number of Twitter followers and greater average number of likes per post had significantly higher average ratings on Healthgrades (p=0.052 and p=0.005, respectively) while surgeons with a greater average number of likes per post had significantly higher average ratings on Vitals (p=0.006). Finally, surgeons with a greater average posting frequency on Instagram had significantly higher average ratings across all websites (p=0.029). CONCLUSION: Shoulder and elbow surgeons who use Twitter and Facebook had significantly higher online ratings. However, the increased use of these platforms in terms of post content, post frequency, comments, and number of followers was not as influential on PRWs. This suggests that social media is an important marketing and outreach method for orthopedic surgeons to improve their ratings and patient reviews.

Outcomes Following Revision Reverse Shoulder Arthroplasty for Infection.

BACKGROUND: In comparison to primary reverse shoulder arthroplasty (RSA) procedures, revision arthroplasty can be a longer and more complex procedure leading to an increased risk of complications. The reported rates of infection in primary RSA range from 1% to 19% and the cost impact on patients and healthcare systems is significant, leading to multiple revision surgeries. The purpose of this study was to evaluate the postoperative outcomes, complications, and revision rates for revision reverse shoulder arthroplasty (rRSA) due to infection compared to rRSA for non-infectious causes. METHODS: Patients who underwent rRSA between 2009 and 2020 by a single fellowship-trained orthopedic surgeon at a single institution were retrospectively identified through a prospectively collected database. Patients were separated into two cohorts based on revision diagnosis: (1) rRSA due to infection (rRSAi), and (2) rRSA due to non-infectious causes (rRSAn). Patient-reported outcome scores (PROs), including the Simple Shoulder Test (SST), Constant score, American Shoulder and Elbow Surgeons (ASES) score, University of California-Los Angeles (UCLA), Shoulder Arthroplasty Smart score (SAS), and active range of motion (ROM) were collected preoperatively and at a minimum one year follow-up. Postoperative complications and revision rates were also collected. RESULTS: A total of 93 patients (n=19 rRSAi group, n=74 rRSAn group) with a mean age of 68 years were included in this analysis. All baseline demographics were comparable between groups. No significant differences were found in preoperative or postoperative PROs and ROM between the two groups. Postoperative complication rates and revision rates were comparable between the groups. CONCLUSION: Revision reverse shoulder arthroplasty due to infection results in similar patient-reported outcome scores, range of motion, and revision rates when compared to rRSA for non-infectious causes. Our results suggest that despite the unique challenges associated with rRSA for infection, patient outcomes do not differ from cases attributed to non-infectious causes. Further efforts are warranted to further validate and contextualize these findings, considering the protentional influence of patient-specific and implant-specific factors.

Telemedicine in orthopaedics during the COVID-19 pandemic: a comparative landscape.

PURPOSE: The purpose of this study was to provide a comprehensive analysis on observed trends regarding the impact of the COVID-19 pandemic on telemedicine application in orthopaedics compared to other procedural, non-emergent specialties. METHODS: This was a retrospective review of all telemedicine and in-person visits at a large single institution from January to December 2020. The number of patient visits, visit type, location, and provider specifics were collected. Comparisons were made between subspecialties (orthopaedic surgery, oncology, family medicine, rheumatology) for analyses. RESULTS: All specialties included were not conducting virtual visits at the beginning of 2020. By April 2020, orthopaedic virtual visits spiked to an all-time high of 33.5% of all patient visits as compared to oncology at 25.5%, rheumatology at 92.9%, and family medicine at 94%. By the end of the study period, orthopaedic virtual visits decreased back down to 6.5% of patient visits compared to oncology at 7.0%, and family medicine (17.4%) and rheumatology (26.2%). Orthopaedic providers practicing greater than 20 years had the highest average virtual visit rates. CONCLUSION: Although the COVID-19 pandemic has posed unique challenges for healthcare providers, there was a great advancement in the rollout and application of telemedicine. To mitigate the spread of infection from coronavirus and given the recent adjustments to reimbursement policies and HIPAA regulations, orthopaedics saw a dramatic expansion of telemedicine since April 2020. The pandemic may have served as a catalyst to adopt telehealth into clinical practice. However, telehealth saw a downtrend trend by December 2020, particularly in procedure-based fields like orthopaedics and oncology.

Change in Body Mass Index and Attributable Risk of New-Onset Hypertension Among Obese Living Kidney Donors.

OBJECTIVE: To examine whether body mass index (BMI) changes modify the association between kidney donation and incident hypertension. BACKGROUND: Obesity increases hypertension risk in both general and living kidney donor (LKD) populations. Donation-attributable risk in the context of obesity, and whether weight change modifies that risk, is unknown. METHODS: Nested case-control study among 1558 adult LKDs (1976-2020) with obesity (median follow-up: 3.6 years; interquartile range: 2.0-9.4) and 3783 adults with obesity in the Coronary Artery Risk Development in Young Adults (CARDIA) and Atherosclerosis Risk in Communities (ARIC) studies (9.2 y; interquartile range: 5.3-15.8). Hypertension incidence was compared by donor status using conditional logistic regression, with BMI change investigated for effect modification. RESULTS: Overall, LKDs and nondonors had similar hypertension incidence [incidence rate ratio (IRR): 1.16, 95% confidence interval (95% CI): 0.94-1.43, P =0.16], even after adjusting for BMI change (IRR: 1.25, 95% CI: 0.99-1.58, P =0.05). Although LKDs and nondonors who lost >5% BMI had comparable hypertension incidence (IRR: 0.78, 95% CI: 0.46-1.34, P =0.36), there was a significant interaction between donor and >5% BMI gain (multiplicative interaction IRR: 1.62, 95% CI: 1.15-2.29, P =0.006; relative excess risk due to interaction: 0.90, 95% CI: 0.24-1.56, P =0.007), such that LKDs who gained weight had higher hypertension incidence than similar nondonors (IRR: 1.83, 95% CI: 1.32-2.53, P <0.001). CONCLUSIONS: Overall, LKDs and nondonors with obesity had similar hypertension incidence. Weight stability and loss were associated with similar hypertension incidence by donor status. However, LKDs who gained >5% saw increased hypertension incidence versus similar nondonors, providing support for counseling potential LKDs with obesity on weight management postdonation.

Targeting a cytokine checkpoint enhances the fitness of armored cord blood CAR-NK cells.

Immune checkpoint therapy has resulted in remarkable improvements in the outcome for certain cancers. To broaden the clinical impact of checkpoint targeting, we devised a strategy that couples targeting of the cytokine-inducible Src homology 2-containing (CIS) protein, a key negative regulator of interleukin 15 (IL-15) signaling, with fourth-generation "armored" chimeric antigen receptor (CAR) engineering of cord blood-derived natural killer (NK) cells. This combined strategy boosted NK cell effector function through enhancing the Akt/mTORC1 axis and c-MYC signaling, resulting in increased aerobic glycolysis. When tested in a lymphoma mouse model, this combined approach improved NK cell antitumor activity more than either alteration alone, eradicating lymphoma xenografts without signs of any measurable toxicity. We conclude that targeting a cytokine checkpoint further enhances the antitumor activity of IL-15-secreting armored CAR-NK cells by promoting their metabolic fitness and antitumor activity. This combined approach represents a promising milestone in the development of the next generation of NK cells for cancer immunotherapy.