Rehabilitation-Specific Predictors of Pain Intensity and Physical Activity Levels in Individuals With Acetabular Dysplasia 6 Months After Periacetabular Osteotomy.

INTRODUCTION: Individuals with acetabular dysplasia often report hip joint instability, pain, and poor hip-related function. Periacetabular osteotomy (PAO) is a surgical procedure that aims to reposition the acetabulum to improve joint congruency and improve pain and function. We aimed to examine the influence of presurgery clinical measures on functional recovery following PAO and the associations among clinical outcomes after PAO. METHODS: We screened 49 potential participants, 28 were enrolled, and 23 completed both study visits (pre-PAO and 6 months post-PAO). We evaluated dynamometer-measured hip and thigh strength, loading patterns during a squat and countermovement jump (CMJ), pain intensity, and device-measured physical activity (PA) levels (light, moderate-to-vigorous PA [MVPA], and daily steps). We used linear regression models to examine the influence of muscle strength (peak torque; limb symmetry index [LSI]) and loading patterns before PAO on pain intensity and PA levels in individuals 6 months following PAO. Additionally, we used Pearson correlation coefficient to examine cross-sectional associations among all variables 6 months following PAO. RESULTS: Lower extremity muscle strength and loading patterns during the squat and CMJ before PAO did not predict pain intensity or device-measured PA levels in individuals 6 months following PAO (p > 0.05). Six months following PAO, higher knee extensor LSI was associated with higher time spent in MVPA (r = 0.56; p = 0.016), higher hip abductor LSI was associated with both lower pain (r = 0.50; p = 0.036) and higher involved limb loading during the squat task (r = 0.59; p = 0.010). Lastly, higher hip flexor LSI was associated with higher CMJ takeoff involved limb loading (r = 0.52; p = 0.021) and higher involved hip extensor strength was associated with higher CMJ landing involved limb loading (r = 0.56; p = 0.012). CONCLUSION: Six months after PAO, higher hip and thigh muscle strength and strength symmetry were associated with lower pain, higher PA levels, and greater normalized limb loading during dynamic movement tasks.

The Relationship Between All-Suture and Solid Medial-Row Anchors and Patient-Reported Outcomes for Double-Row Suture Bridge Rotator Cuff Repair.

Background: The use of all-suture anchors for rotator cuff repair is increasing. Potential benefits include decreased bone loss and decreased damage to the chondral surface. Minimal evidence exists comparing outcomes among medial-row anchor fixation methods in double-row suture bridge rotator cuff repair. Purpose: To compare the clinical outcomes between all-suture and solid medial-row anchors in double-row suture bridge rotator cuff repair. Study Design: Case series; Level of evidence, 4. Methods: A total of 352 patients (mean age at surgery, 60.3 years) underwent double-row suture bridge rotator cuff repair at our institution. Patients were separated into 2 groups based on whether they underwent all-suture (n = 280) or solid (n = 72) anchor fixation for the medial row. Outcomes data were collected via an ongoing longitudinal data repository or through telephone calls (minimum follow-up time, 2.0 years; mean follow-up time, 3.0 years). Outcomes were evaluated using the American Shoulder and Elbow Surgeons (ASES) standardized shoulder assessment form and the visual analog scale (VAS). The same rehabilitation protocol was administered to all patients. The proportions of patients meeting previously published Patient Acceptable Symptom State (PASS) thresholds were calculated for the outcome measures, and outcome scores and the proportions of patients meeting PASS thresholds between groups were compared using linear and logistic regression, respectively. Results: The groups did not differ in terms of age at surgery, sex distribution, rotator cuff tear size, or number of medial-row anchors used. The solid anchor group had a longer follow-up time compared with the all-suture anchor group (3.6 ± 0.7 vs 2.8 ± 0.8 years, respectively; P < .01). After controlling for follow-up time, the solid and all-suture anchor groups did not differ in ASES scores (89.6 ± 17.8 vs 88.8 ± 16.7, respectively; P = .44) or VAS scores (1.1 ± 2.1 vs 1.2 ± 2.1, respectively; P = .37). Similarly, after controlling for follow-up time, the solid and all-suture anchor groups did not differ in the proportions of patients meeting PASS cutoffs for the ASES (84.7% vs 80.7%, respectively; P = .44) or the VAS (80.6% vs 75.0%, respectively; P = .83). Conclusion: Double-row suture bridge rotator cuff repair using all-suture anchors for medial-row fixation demonstrated similar excellent clinical outcomes to rotator cuff repair using solid medial-row anchors.

Pre- and Post-Operative Pain Intensity and Physical Activity Levels in Individuals with Acetabular Dysplasia Undergoing Periacetabular Osteotomy: A Prospective Cohort Study.

Background: Acetabular dysplasia (AD) causes pain, limited function, and development of early hip osteoarthritis. Periacetabular osteotomy (PAO) is a surgical treatment for AD that aims to reposition the acetabulum to reduce pain and improve function. Purpose: To examine pain recovery and physical activity (PA) before and during the six months after PAO. Study Design: Case series, prospective. Methods: Individuals with AD scheduled for PAO were enrolled. Pain intensity was evaluated before PAO and at one week and one, three, and six months following PAO. PA levels was evaluated before and six months following PAO using accelerometers (time spent in sedentary behavior, light PA, moderate-to-vigorous PA [MVPA], and daily steps) and the International Physical Activity Questionnaire (IPAQ; time spent in walking and in MVPA). Pain improvements was examined over time following PAO using a repeated-measures one-way ANOVA as well as improvements in PA levels before and six months after PAO using paired-sample t tests. In addition, time spent in MVPA was qualitatively summarized at each time point (before and six months after PAO) measured by both the accelerometers and IPAQ. Results: Out of 49 screened participants, 28 were enrolled, and 23 individuals (22 females; age=23.1±7.9 years) completed both study visits. Compared to pre-PAO pain, participants reported significant improvements in pain at one month and onward following PAO (p\<0.011). However, PA levels at six months following PAO did not differ from pre-PAO PA levels (p>0.05). Qualitatively, participants reported spending more time in MVPA recorded by the IPAQ (pre-PAO=73.3±150.2 mins/day; six-months after PAO=121.2±192.2 mins/day), compared with MVPA recorded by accelerometers (pre-PAO=22.6±25.2 mins/day; six-months after PAO=25.0±21.4 mins/day). Conclusions: Individuals with AD reported significant pain reduction at one month and up to six months after PAO, but PA levels did not change six months after PAO compared to baseline testing. Future studies should consider examining longitudinal pain recovery and PA improvements over longer periods of time with larger samples of individuals with AD undergoing PAO and identifying modifiable factors to minimize pain and increase PA participation. Level of Evidence: III.

Long-term Outcomes of Multiligament Knee Injuries in American Football Players.

BACKGROUND: Long-term outcomes for isolated anterior cruciate ligament (ACL) reconstructions in competitive American football athletes are well reported in the literature, but little data currently exist regarding multiligament knee injury (MLKI) reconstruction outcomes. PURPOSE: To examine patient-reported and return-to-sport outcomes of competitive American football athletes who underwent primary, single-staged, multiligament knee reconstruction. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: We identified patients from our institution's prospectively collected data repository between 2001 and 2020 who underwent single-staged surgical reconstruction of an MLKI sustained during competitive participation in American football. We assessed patient-reported outcomes at a minimum of 2 years after surgery using the International Knee Documentation Committee (IKDC) Subjective Knee Form and questions regarding surgical satisfaction and return to sport. Successful return to sport was defined as a return to preinjury level of competition. We summarized all outcome data and compared outcomes between 2-ligament and >2-ligament groups and between ACL-only MLKI injury and bicruciate MLKI injury groups using independent t test for IKDC scores and chi-square test for return to sport. Additionally, we evaluated predictors of postoperative IKDC scores using linear regression and predictors of return to sport using logistic regression. RESULTS: Outcome data were successfully collected for 53 of 73 total eligible patients (73%; mean follow-up time, 7.7 ± 4.0 years; all male; mean age at surgery, 18.1 ± 2.7 years). The mean postoperative IKDC score was 84 ± 16. The most common level of preinjury competition was high school (n = 36; 68%), followed by college (n = 10; 19%). Seven patients did not return to sport competition at any level due to limitations from their knee surgery, and 82% of patients that attempted to return to preinjury level of sport were able to do so. A total of 50 patients (94%) were satisfied or very satisfied with their surgical outcome. The 2-ligament (n = 39) and >2-ligament (n = 14) groups did not significantly differ in IKDC scores (P = .96) or proportions with successful return to sport (P = .77). Similarly, the ACL-MLKI injury (n = 39) and bicruciate MLKI injury (n = 14) groups did not significantly differ in IKDC scores (P = .89) or proportions with successful return to sport (P = .77). Age and body mass index were not significantly associated with IKDC scores or successful return to sport at follow-up (all P > .05). CONCLUSION: This study may represent the largest cohort of competitive American football athletes evaluated for longitudinal outcomes after multiligament knee reconstruction. Despite the severity of these injuries, we found good knee-related function and that the large majority of athletes who attempted to return to sport were successful. The majority of athletes (94%) were satisfied with their operative treatment.

Lymphovascular Invasion in Cutaneous Squamous Cell Carcinoma.

BACKGROUND: Although there is a large body of literature regarding risk stratification and outcomes for perineural invasion (PNI) in cutaneous squamous cell carcinoma (cSCC), there is a relative paucity of studies exploring the role of lymphovascular invasion (LVI) in cSCC and a lack of clear evidence-based guidelines for how to manage patients with these tumors. OBJECTIVE: This article is intended to review the available literature regarding LVI in cSCC and formulate evidence-based recommendations for clinical management. METHODS AND MATERIALS: A literature review was conducted using PubMed to find relevant articles relating to outcomes and management of primary cSCC with LVI. RESULTS: The available literature suggests that LVI is a major risk factor for poor outcomes and increased morbidity and mortality in cSCC. CONCLUSION: Lymphovascular invasion is a very high-risk feature that should place these tumors in the highest-risk category, and management of these tumors should be similar to that of squamous cell carcinoma with PNI.

Clinic-based perspectives on the integration of patient-reported outcomes (PROs) in a tertiary cancer center.

PURPOSE: This study examines providers' and clinic staff's perspectives on patient-reported outcomes (PROs) implementation at an academic medical center. METHODS: An anonymous and voluntary survey was administered to Henry Ford Cancer providers and clinic staff 18 months after PROs program implementation in September 2020, to obtain their feedback on perceived barriers, impact on workflows, and PROs administration frequency in routine cancer care. RESULTS: A total of 180 providers and 40 clinic staff were invited to complete the survey; 31% and 63% completed the survey, respectively. Approximately 68% of providers reported that electronically integrated PROs scores were either beneficial or somewhat beneficial to their patients, while only 28% of the clinic staff reported that PROs were beneficial or somewhat beneficial to patients. According to the clinic staff, the most common barriers to PROs completion included lack of patients' awareness of the utility of the program with respect to their care, patients' health status at check-in, and PROs being offered too frequently. CONCLUSION: There is favorable acceptance of the PROs program by providers, but clinic staff found it less favorable. Interventions to address barriers and improve program engagement are needed to ensure broad adoption of PROs in oncology practice.

Limited Access to Aortic Valve Procedures in Socioeconomically Disadvantaged Areas.

BACKGROUND: To explore how differences in local socioeconomic deprivation impact access to aortic valve procedures and the treatment of aortic valve disease, in comparison to other open and minimally invasive surgical procedures. METHODS AND RESULTS: Procedure volume data were obtained from the Healthcare Cost and Utilization Project from 18 states from 2016 to 2019 and merged with area deprivation index data, an index of zip code-level socioeconomic distress. We estimate the relationship between local deprivation ranking and differences in volumes of aortic valve replacement, which include transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR), versus coronary artery bypass graft surgery and laparoscopic colectomy (LC). All regressions control for state and year fixed effects and an array of zip code-level characteristics. TAVR procedures have increased over time across all zip codes. The rate of increase is negatively correlated with deprivation ranking, regardless of the higher share of hospitalizations per population in high deprivation areas. Distributional analysis further supports these findings, showing that lower area deprivation index areas account for a disproportionately large share of SAVR, TAVR, and LC procedures in our sample relative to their share of all hospitalizations in our sample. By comparison, the cumulative distribution of coronary artery bypass graft procedures was nearly identical to that of total hospitalizations, suggesting that this procedure is equitably distributed. Regressions show high area deprivation index areas have lower prevalence of SAVR (ß=-15.1%, [95% CI, -26.8 to -3.5]), TAVR (ß=-9.1%, [95% CI, -18.0 to -0.2]), and LC (ß=-19.9%, [95% CI, -35.4 to -4.4]), with no statistical difference in the prevalence of coronary artery bypass graft (ß=-2.5%, [95% CI, -12.7 to 7.6]), a widespread and commonly performed procedure. In the population aged ≥80 years, results show high area deprivation index areas have a lower prevalence of TAVR (ß=-11.9%, [95% CI, -18.7 to -5.2]) but not SAVR (ß=-0.8%, [95% CI, 8.1 to 6.3]), LC (ß=-3.5%, [95% CI, -13.4 to -6.4]), or coronary artery bypass graft (ß=5.2%, [95% CI, -1.1 to 1.1]). CONCLUSIONS: People living in high deprivation areas have less access to life-saving technologies, such as SAVR, and even moreso to device-intensive minimally invasive procedures such as TAVR and LC.

Rare adrenal cavernous hemangioma: a case report highlighting diagnostic challenges.

Introduction: Adrenal cavernous hemangiomas are rare benign vascular tumors that pose significant diagnostic challenges. Despite their benign nature, features overlapping with malignancies often complicate management decisions. Case presentation: A 64-year-old male presented with a 4.4 cm necrotic left adrenal mass discovered incidentally on imaging. His medical history included papillary thyroid carcinoma, with subsequent thyroidectomy and radioactive iodine ablation. Evaluations for hiccups revealed multiple lung nodules, hypertrophic cardiomyopathy, and anemia. Given the patient's previous cancer history, elevated aldosterone/renin ratio, and mass size, our multidisciplinary tumor board decided to proceed with a left adrenalectomy. Post-surgical pathology confirmed a diagnosis of adrenal cavernous hemangioma. Conclusion: The occurrence of ambiguous adrenal mass with other pathologies, such as our patient's papillary thyroid carcinoma, complicates the diagnostic and therapeutic landscape. As demonstrated in our case, opting for surgery remains a viable solution for adrenal cavernous hemangiomas, especially for masses greater than 4 cm. Interdisciplinary collaboration, exemplified by our tumor board's decision-making process, is crucial for optimal management. This case underscores the need for a multifaceted approach when confronting adrenal masses with such diagnostic ambiguity.

Outcomes of Double-Row Rotator Cuff Repair Using a Novel All-Suture Soft Anchor Medial Row.

Background: Few studies have examined the short-term clinical outcomes of rotator cuff repair (RCR) with all-suture anchors for medial row anchor fixation. Purpose: To evaluate clinical outcomes of double-row suture bridge RCR using a novel all-suture medial row anchor. Study Design: Case series; Level of evidence, 4. Methods: We enrolled 179 patients before double-row suture bridge RCR (mean age at surgery, 60.0 years; 63% male patients) at a single institution. All patients underwent RCR with all-suture anchor fixation for the medial row and solid anchor fixation for the lateral row. Preoperative (baseline) and follow-up (minimum follow-up time of 2 years; mean, 2.5 years) clinical outcomes were compared using the American Shoulder and Elbow Surgeons (ASES) score and a 10-point numeric pain rating scale (NPRS). We calculated the proportions of patients meeting previously published Patient Acceptable Symptom State (PASS) thresholds for the ASES (≥78.0) and NPRS (≤1.7). We further compared baseline and follow-up outcome scores and the proportions of patients meeting PASS thresholds using paired t tests and McNemar tests, respectively, and calculated effect size to quantify the magnitude of change from baseline to follow-up. Results: Values significantly improved from baseline to follow-up for ASES (from 45.3 ± 19.8 to 87.3 ± 17.1) and NPRS (from 5.2 ± 2.5 to 1.4 ± 2.1). The proportion of patients meeting PASS thresholds also significantly improved for the ASES (from 6% to 77%) and the NPRS (from 7% to 72%). The magnitude of baseline to follow-up change for all measures was large (all effect sizes ≥1.5). Conclusion: Our study demonstrated excellent short-term clinical outcomes and substantial improvements for patients undergoing double-row suture bridge RCR with all-suture anchors for medial row fixation.

High ploidy large cytoplasmic megakaryocytes are hematopoietic stem cells regulators and essential for platelet production.

Megakaryocytes (MK) generate platelets. Recently, we and others, have reported MK also regulate hematopoietic stem cells (HSC). Here we show high ploidy large cytoplasmic megakaryocytes (LCM) are critical negative regulators of HSC and critical for platelet formation. Using a mouse knockout model (Pf4-Srsf3Δ/Δ) with normal MK numbers, but essentially devoid of LCM, we demonstrate a pronounced increase in BM HSC concurrent with endogenous mobilization and extramedullary hematopoiesis. Severe thrombocytopenia is observed in animals with diminished LCM, although there is no change in MK ploidy distribution, uncoupling endoreduplication and platelet production. When HSC isolated from a microenvironment essentially devoid of LCM reconstitute hematopoiesis in lethally irradiated mice, the absence of LCM increases HSC in BM, blood and spleen, and the recapitulation of thrombocytopenia. In contrast, following a competitive transplant using minimal numbers of WT HSC together with HSC from a microenvironment with diminished LCM, sufficient WT HSC-generated LCM regulates a normal HSC pool and prevents thrombocytopenia. Importantly, LCM are conserved in humans.

Interferon Gamma-Inducible NAMPT in Melanoma Cells Serves as a Mechanism of Resistance to Enhance Tumor Growth.

(1) Background: Immune cells infiltrate the tumor microenvironment and secrete inflammatory cytokines, including interferons (IFNs), to drive antitumor responses and promote tumor clearance. However, recent evidence suggests that sometimes, tumor cells can also harness IFNs to enhance growth and survival. The essential NAD+ salvage pathway enzyme nicotinamide phosphoribosyltransferase (NAMPT) gene is constitutively expressed in cells during normal homeostasis. However, melanoma cells have higher energetic demands and elevated NAMPT expression. We hypothesized that interferon gamma (IFNγ) regulates NAMPT in tumor cells as a mechanism of resistance that impedes the normal anti-tumorigenic effects of IFNγ. (2) Methods: Utilizing a variety of melanoma cells, mouse models, Crispr-Cas9, and molecular biology techniques, we explored the importance of IFNγ-inducible NAMPT during melanoma growth. (3) Results: We demonstrated that IFNγ mediates the metabolic reprogramming of melanoma cells by inducing Nampt through a Stat1 binding site in the Nampt gene, increasing cell proliferation and survival. Further, IFN/STAT1-inducible Nampt promotes melanoma in vivo. (4) Conclusions: We provided evidence that melanoma cells directly respond to IFNγ by increasing NAMPT levels, improving their fitness and growth in vivo (control n = 36, SBS KO n = 46). This discovery unveils a possible therapeutic target that may improve the efficacy of immunotherapies involving IFN responses in the clinic.

Clinical outcomes of osteochondritis dissecans lesions of the capitellum treated with arthroscopy with a mean follow-up period of 8.3 years.

BACKGROUND AND HYPOTHESIS: Although numerous studies exist evaluating the short-term clinical outcomes of patients who have undergone elbow arthroscopy for osteochondritis dissecans (OCD) of the capitellum, the literature on minimum 2-year clinical outcomes in a large cohort of patients is limited. We hypothesized that the clinical outcomes of patients treated arthroscopically for OCD of the capitellum would be favorable, with improved postoperative subjective functional and pain scores and with an acceptable return-to-play rate. METHODS: A retrospective analysis of a prospectively collected surgical database was performed to identify all patients treated surgically for OCD of the capitellum at our institution from January 2001 to August 2018. The inclusion criteria for this study included a diagnosis of OCD of the capitellum treated arthroscopically with a minimum 2-year follow-up period. The exclusion criteria included any prior surgical treatment on the ipsilateral elbow, missing operative reports, and cases in which any portion of the surgical procedure was performed in an open manner. Follow-up was performed by telephone using multiple patient-reported outcome questionnaires: American Shoulder and Elbow Surgeons-Elbow (ASES-e), Andrews-Carson, and Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow Score (KJOC) questionnaires and our institution-specific return-to-play questionnaire. RESULTS: After the inclusion and exclusion criteria were applied to our surgical database, 107 eligible patients were identified. Of these, 90 were successfully contacted, for a follow-up rate of 84%. The mean age was 15.2 years, and the mean follow-up time was 8.3 years. A subsequent revision procedure was performed in 11 patients, for a 12% failure rate in these patients. The ASES-e pain score was an average of 4.0 on a maximum pain scale of 100, the ASES-e function score was an average of 34.5 of a maximum of 36, and the surgical satisfaction score was an average of 9.1 of 10. The average Andrews-Carson score was 87.1 of 100, and the average KJOC score for overhead athletes was 83.5 of 100. Additionally, of the 87 patients evaluated who played sports at the time of their arthroscopy, 81 (93%) returned to play. CONCLUSION: This study demonstrated an excellent return-to-play rate and satisfactory subjective questionnaire scores with a 12% failure rate following arthroscopy for OCD of the capitellum with a minimum 2-year follow-up period.

A history of eponym usage in hip and pelvis radiography part 2: the adult hip.

Eponyms, while inherently flawed, remain a constant in medical vernacular, especially in orthopaedic surgery. It is essential to understand how these eponyms came to be named and for whom they were named after in order to understand their correct usage and definitions. In this second part of a 2-part review, we describe the history of eponym usage in the radiography of the adult hip; who, when, what, where, and how. We hope to provide a historical perspective of interest, resolve any controversies in semantic definitions, and create a comprehensive library of eponymous terms related to adult hip radiography.

Pharmacological tumor PDL1 depletion with chlorambucil treats ovarian cancer and melanoma: improves antitumor immunity and renders anti-PDL1-resistant tumors anti-PDL1-sensitive through NK cell effects.

BACKGROUND: Tumor intracellular programmed cell death ligand-1 (PDL1) mediates pathologic signals that regulate clinical treatment responses distinctly from surface-expressed PDL1 targeted by αPDL1 immune checkpoint blockade antibodies. METHODS: We performed a drug screen for tumor cell PDL1 depleting drugs that identified Food and Drug Administration (FDA)-approved chlorambucil and also 9-[2-(phosphonomethoxy)ethyl] guanine. We used in vitro and in vivo assays to evaluate treatment and signaling effects of pharmacological tumor PDL1 depletion focused on chlorambucil as FDA approved, alone or plus αPDL1. RESULTS: PDL1-expressing mouse and human ovarian cancer lines and mouse melanoma were more sensitive to chlorambucil-mediated proliferation inhibition in vitro versus corresponding genetically PDL1-depleted lines. Orthotopic peritoneal PDL1-expressing ID8agg ovarian cancer and subcutaneous B16 melanoma tumors were more chlorambucil-sensitive in vivo versus corresponding genetically PDL1-depleted tumors. Chlorambucil enhanced αPDL1 efficacy in tumors otherwise αPDL1-refractory, and improved antitumor immunity and treatment efficacy in a natural killer cell-dependent manner alone and plus αPDL1. Chlorambucil-mediated PDL1 depletion was relatively tumor-cell selective in vivo, and treatment efficacy was preserved in PDL1KO hosts, demonstrating tumor PDL1-specific treatment effects. Chlorambucil induced PDL1-dependent immunogenic tumor cell death which could help explain immune contributions. Chlorambucil-mediated PDL1 reduction mechanisms were tumor cell-type-specific and involved transcriptional or post-translational mechanisms, including promoting PDL1 ubiquitination through the GSK3ß/ß-TRCP pathway. Chlorambucil-mediated tumor cell PDL1 depletion also phenocopied genetic PDL1 depletion in reducing tumor cell mTORC1 activation and tumor initiating cell content, and in augmenting autophagy, suggesting additional treatment potential. CONCLUSIONS: Pharmacological tumor PDL1 depletion with chlorambucil targets tumor-intrinsic PDL1 signaling that mediates treatment resistance, especially in αPDL1-resistant tumors, generates PDL1-dependent tumor immunogenicity and inhibits tumor growth in immune-dependent and independent manners. It could improve treatment efficacy of selected agents in otherwise treatment-refractory, including αPDL1-refractory cancers, and is rapidly clinically translatable.

Clinical outcomes and return to play in softball players following SLAP repair or biceps tenodesis.

BACKGROUND: Shoulder pain due to labral tears and biceps tendonitis is commonly found in softball players. Surgical options include labral repair and biceps tenodesis. Although past studies are limited by heterogeneous study groups from multiple sports, this is the first study that assesses clinical outcomes and return to play rates for fast-pitch softball players. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate the clinical outcomes and return to play for fast-pitch softball players treated for a superior labrum anterior posterior (SLAP) tear and recalcitrant biceps tendonitis with a biceps tenodesis compared with a traditional SLAP repair. We hypothesized that the biceps tenodesis would have comparable outcomes with a faster return to play compared with SLAP repair. METHODS: We performed a retrospective analysis on fast-pitch softball players treated surgically for SLAP tear, recalcitrant biceps tendonitis, or a combination between 2001 and 2019 at our institution. Inclusion criteria were fast-pitch softball players who underwent biceps tenodesis or a SLAP repair with greater than 2-year follow-up. Exclusion criteria involved slow-pitch softball players, patients with less than 2-year follow-up, and patients who had undergone concomitant procedures on the ipsilateral shoulder at the time of SLAP repair or biceps tenodesis. Follow-up was either self-reported through OBERD, a patient-reported outcomes (PRO)-managing software, or achieved over the phone. Follow-up data included American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form score, Andrews Carson Score, Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow Score, Numeric Rating Scale for Pain, and our institution-specific return-to-play questionnaire. We statistically compared players who underwent biceps tenodesis or a SLAP repair, and compared pitchers with position players using Student t tests and Fisher exact test with statistical significance determined to be P < .05. RESULTS: From 60 eligible patients identified, follow-up outcome data were successfully captured for 47 (78%). Of the 18 SLAP repair patients, 17 (94%) returned to full competition at an average of 7.9 months. Of the 29 patients who underwent biceps tenodesis, 27 (93%) returned to full competition at an average of 7.1 months. Statistical analysis of PRO scores for each group found no significant differences between any of the measures used to evaluate patient outcomes, including no statistical difference in pitchers compared with position players. CONCLUSION: In conclusion, this study demonstrated comparable outcomes between SLAP repairs and biceps tenodesis procedures among our study group of fast-pitch softball players. There was no significant difference between RTP times between the 2 groups.

Artificial Intelligence for Automated Implant Identification in Total Hip Arthroplasty: A Multicenter External Validation Study Exceeding Two Million Plain Radiographs.

BACKGROUND: The surgical management of complications after total hip arthroplasty (THA) necessitates accurate identification of the femoral implant manufacturer and model. Automated image processing using deep learning has been previously developed and internally validated; however, external validation is necessary prior to responsible application of artificial intelligence (AI)-based technologies. METHODS: We trained, validated, and externally tested a deep learning system to classify femoral-sided THA implants as one of the 8 models from 2 manufacturers derived from 2,954 original, deidentified, retrospectively collected anteroposterior plain radiographs across 3 academic referral centers and 13 surgeons. From these radiographs, 2,117 were used for training, 249 for validation, and 588 for external testing. Augmentation was applied to the training set (n = 2,117,000) to increase model robustness. Performance was evaluated by area under the receiver operating characteristic curve, sensitivity, specificity, and accuracy. Implant identification processing speed was calculated. RESULTS: The training and testing sets were drawn from statistically different populations of implants (P < .001). After 1,000 training epochs by the deep learning system, the system discriminated 8 implant models with a mean area under the receiver operating characteristic curve of 0.991, accuracy of 97.9%, sensitivity of 88.6%, and specificity of 98.9% in the external testing dataset of 588 anteroposterior radiographs. The software classified implants at a mean speed of 0.02 seconds per image. CONCLUSION: An AI-based software demonstrated excellent internal and external validation. Although continued surveillance is necessary with implant library expansion, this software represents responsible and meaningful clinical application of AI with immediate potential to globally scale and assist in preoperative planning prior to revision THA.

Fifty years of impact on treating bone disease: a commentary on Gasser et al.

The precise control of whole-body calcium is essential for the maintenance of normal physiological function. Disruptions in calcium homeostasis can lead to pathology including osteoporosis, kidney stone formation, and cardiac arrythmias. During the 1960s and early 1970s, a full understanding of calcium metabolism was still emerging. This commentary spotlights a seminal Clinical Science paper published in 1972 that significantly advanced the field and contributed to the eventual approval of bisphosphonate drugs commonly used to treat postmenopausal osteoporosis, cancer metastases, and other calcium disorders.

Epithelial sodium channels in macrophage migration and polarization: role of proinflammatory cytokines TNFα and IFNγ.

Migration of monocytes-macrophages plays an important role in phagocytosis of pathogens and cellular debris in a variety of pathophysiological conditions. Although epithelial Na+ channels (ENaCs) are required for normal migratory responses in other cell types, their role in macrophage migration signaling is unknown. To address this possibility, we determined whether ENaC message is present in several peripheral blood monocyte cell populations and tissue-resident macrophages in healthy humans using the Human Protein Atlas database (www.proteinatlas.org) and the mouse monocyte cell line RAW 264.7 using RT-PCR. We then determined that selective ENaC inhibition with amiloride inhibited chemotactic migration (∼50%), but not phagocytosis, of the mouse monocyte-macrophage cell line RAW 264.7. Furthermore, we generated a cell line stably expressing an NH2-terminal truncated αENaC to interrupt normal channel trafficking and found it suppressed migration. Prolonged exposure (48 h) of RAW 264.7 cells to proinflammatory cytokines interferon γ (IFNγ) and/or tumor necrosis factor α (TNFα) inhibited RAW 264.7 migration and abolished the amiloride (1 µM)-sensitive component of migration, a finding consistent with ENaC downregulation. To determine if proinflammatory cytokines regulate αENaC protein expression, cells were exposed to proinflammatory cytokines IFNγ (10 ng/mL, last 48 h) and TNFα (10 ng/mL, last 24 h). By Western blot analysis, we found whole cell αENaC protein is reduced ≥50%. Immunofluorescence demonstrated heterogeneous αENaC inhibition. Finally, we found that overnight exposure to amiloride stimulated morphological changes and increased polarization marker expression. Our findings suggest that ENaC may be a critical molecule in macrophage migration and polarization.

Clinical Outcomes of Ulnar Collateral Ligament Surgery in Nonthrowing Athletes.

BACKGROUND: Ulnar collateral ligament (UCL) surgery continues to demonstrate excellent clinical outcomes and a high return-to-play (RTP) rate with a low complication rate. Recent studies have demonstrated similar clinical outcomes for baseball players who have undergone either UCL reconstruction or UCL repair. In comparison, few studies have assessed the clinical outcomes of UCL surgery for nonthrowing athletes. PURPOSE/HYPOTHESIS: The primary objective of this study is to provide clinical outcomes of UCL surgery performed in nonthrowing athletes at a single institution with a minimum 2-year follow-up. Our hypothesis was that these patients would have similar clinical outcomes, complication rates, and RTP rates when compared with throwing athletes. LEVEL OF EVIDENCE: Case series; Level of evidence, 4. METHODS: From our longitudinal elbow registry, 40 nonthrowing athletes were identified who underwent UCL surgery (repair or reconstruction) between 2011 and 2019. Participant characteristics were recorded: age, sex, laterality, arm dominance, sport, level of competition, and type of surgery (UCL repair or reconstruction). Outcomes included RTP rate and average time, American Shoulder and Elbow Surgeons (ASES) scores, and complications. RESULTS: From the 40 patients eligible for inclusion in this study with a minimum 2-year follow-up, 37 (93%) were successfully contacted: 16 male (43%) and 21 female (57%). Mean ± standard deviation age at the time of surgery was 18.0 ± 3.7 years. From the 37 technical procedures, 28 (76%) were UCL repairs and 9 (24%) were UCL reconstructions. For these patients, 15 (41%) had partial tears, 20 (54%) had complete tears, 1 (3%) had a medial epicondyle avulsion, and 1 (3%) had an unspecified pathology. Sports included football (n = 11), gymnastics (11), cheerleading (7), wrestling (4), volleyball (2), basketball (1), and acrobatics (1). Quarterbacks were excluded from the football patients, as quarterbacks are throwing athletes. Level of competition included high school (n = 26), college (8), professional (2), and youth sports (1). The RTP rate was 93% (26/28) at a mean 7.4 months for UCL repair and 100% (9/9) at a mean 10.0 months for UCL reconstruction. Mean ASES scores were 94.4 and 98.7 for UCL repair and reconstruction, respectively. Complications were low, with 2 patients in the UCL repair group requiring ulnar nerve transposition for ulnar nerve paresthesia. CONCLUSION: In nonthrowing athletes, patients undergoing UCL repair and UCL reconstruction show favorable outcomes at minimum 2-year follow-up. RTP and clinical outcomes are consistent with previous studies in baseball players as well as a parallel ongoing study conducted on non-baseball throwing athletes.

Biallelic pathogenic variants in COX11 are associated with an infantile-onset mitochondrial encephalopathy.

Primary mitochondrial diseases are a group of genetically and clinically heterogeneous disorders resulting from oxidative phosphorylation (OXPHOS) defects. COX11 encodes a copper chaperone that participates in the assembly of complex IV and has not been previously linked to human disease. In a previous study, we identified that COX11 knockdown decreased cellular adenosine triphosphate (ATP) derived from respiration, and that ATP levels could be restored with coenzyme Q10 (CoQ10 ) supplementation. This finding is surprising since COX11 has no known role in CoQ10 biosynthesis. Here, we report a novel gene-disease association by identifying biallelic pathogenic variants in COX11 associated with infantile-onset mitochondrial encephalopathies in two unrelated families using trio genome and exome sequencing. Functional studies showed that mutant COX11 fibroblasts had decreased ATP levels which could be rescued by CoQ10 . These results not only suggest that COX11 variants cause defects in energy production but reveal a potential metabolic therapeutic strategy for patients with COX11 variants.