Tendon transfers in the setting of shoulder arthroplasty.

Background: Tendon transfers in conjunction with reverse total shoulder arthroplasty can significantly improve functional outcomes in patients with glenohumeral arthritis and irreparable rotator cuff deficiency. There have been multiple promising new techniques described within the last 20 years that shoulder surgeons should become familiar with. Methods: The authors reviewed the literature on tendon transfers in the setting of reverse total shoulder arthroplasty. Procedures to restore various shoulder functions were described including surgical anatomy, techniques, pearls and pitfalls, and photos. Results: Subscapularis insufficiency can be reconstructed with a pectoralis major transfer or latissimus dorsi transfer, with the latter having better clinical outcomes and a more anatomic line of pull. Posterosuperior rotator cuff deficiency can be reconstructed with a latissimus transfer (L'Episcopo transfer) or lower trapezius transfer, with the latter proving superior in biomechanical and short-term studies. Deltoid deficiency can be reconstructed with a pedicled upper pectoralis major transfer. Massive proximal humerus bone loss can be reconstructed with an allograft-prosthetic composite, and any of the aforementioned transfers can be utilized in this setting as well. Conclusion: Tendon transfers in conjunction with reverse shoulder arthroplasty can significantly improve functional outcomes in patients with glenohumeral arthritis and irreparable rotator cuff deficiency. There have been multiple promising new techniques described within the last 20 years that shoulder surgeons should become familiar with.

Structural Bone Grafting with Reverse Shoulder Arthroplasty for Osteoarthritis with Severe Glenoid Bone Loss: outcomes using a long post.

INTRODUCTION: Severe posterior glenoid bone loss with glenohumeral osteoarthritis with an intact rotator cuff can be managed with reverse shoulder arthroplasty but requires lateralization and version correction to avoid potential complications, such as instability, notching and implant failure. Angled bone grafting with humeral head autograft can provide durable glenoid bone stock, but results have been mixed. The purpose of this study was to evaluate patient-reported and objective outcomes as well as complication and failure rates for patients who underwent angled humeral head autografting for severe retroversion. METHODS: All patients who underwent a primary RSA with angled humeral head autograft and Stryker Tornier long central post baseplate for severe glenoid bone loss in the setting of glenohumeral osteoarthritis with an intact rotator cuff at our institution between November 2018 and February of 2022 were identified. Individuals with a primary diagnosis of osteoarthritis and preoperative glenoid retroversion of ≥30° were included. Patients undergoing revision procedures, planned two-stage arthroplasty were excluded. Differences in pre- and postoperative range of motion, as well as patient-reported outcomes were assessed. Intraoperative complications, postoperative complications, and re-operation rates were analyzed. RESULTS: A total of 24 shoulders in 23 patients (61% male), with a mean age of 65.6 years were included. Average preoperative retroversion was 37.4° (range: 30° - 51°). Mean follow-up was 2.9 years (range: 2 - 4.3 years). Significant improvements were found in flexion, abduction, and external rotation. Patient-reported subjective outcomes were excellent, with average ASES score of 93.6 and average SSV 93.8%. Sixteen (67%) shoulders received postoperative CT scans and all were found to have incorporated. Complications included one shoulder hematoma requiring incision and drainage without revision, and a post-traumatic fracture of the inferior glenoid screw at 11 months, requiring revision RSA with bone grafting. No atraumatic catastrophic failures occurred due to component loosening. CONCLUSION: This study suggests that using angled humeral head bone grafting is a good solution for version correction in extreme posterior glenoid bone loss. Significant improvements are reported in ROM, pain, and subjective functional scores, with excellent graft incorporation rates and a low complication profile at early follow-up. Further work should focus on gathering higher levels of evidence, detailed radiographic analyses and exploring humeral head bone grafting for other indications.

Superficial Branch of the Radial Nerve Versus Sural Nerve Grafting After Traumatic Adult Brachial Plexus Injury.

The purpose of this study was to compare two sources of nerve graft for brachial plexus reconstruction: the denervated superficial branch of the radial nerve (SBRN) and the sural nerve. Ninety-seven patients who underwent brachial plexus reconstruction with denervated SBRN nerve (24 patients with 24 grafts) or with sural nerve grafting (73 patients with 83 nerve grafts) were included. The two groups were compared with respect to postoperative muscle reinnervation, disabilities of the arm, shoulder, and hand (DASH) scores. In the SBRN group, only four (17%) of the nerve grafts provided grade III or higher muscle function. In the sural nerve group, 31 (37%) of the nerve grafts provided grade III or higher muscle function. Smoking had a negative impact on muscle recovery. Denervated SBRN grafts are associated with inferior outcomes when compared with sural nerve grafts in the treatment of traumatic adult brachial plexus injuries. (Journal of Surgical Orthopaedic Advances 33(2):080-083, 2024).

Determining the Optimal Intramedullary Screw Canal Fill Ratio in Length Unstable Metacarpal Fractures: A Biomechanical Investigation.

PURPOSE: Intramedullary (IM) screw fixation is gaining popularity in the treatment of metacarpal fractures. Despite its rapid adoption, there is a paucity of evidence regarding parameters to optimize effectiveness. This study aimed to quantify the relationship between stability, IM screw size, and canal fill using a cadaveric model. METHODS: Thirty cadaveric metacarpals (14 index, 13 middle, and three ring fingers; mean age: 58.3 years, range: 48-70) were selected to allow for canal fill ratios of 0.7-1.1 for screws sized 3.0, 3.5, and 4.5 mm. Metacarpals underwent a 45° volar-dorsal osteotomy at the midpoint before fixation with an IM screw. Specimens were subjected to 100 cycles of loading at 10 N, 20 N, and 30 N before load-to-failure testing. Correlation coefficients for angular displacement on the final cycle at each load, peak load to failure, and average stiffness were assessed. RESULTS: Correlation coefficients for the angular displacement on the 100th cycle were as follows: 10 N, R = 0.62, 20 N, R = 0.57, and 30N, R = 0.58. Correlation values for peak load to failure as a function of canal fit were as follows: 3.0 mm, R = 0.5, 3.5 mm, R = 0.17, and 4.5 mm, R = 0.44. The canal fill ratio that intersected the line-of-best fit at an angular deformity of 10° was 0.74. Average peak forces for 3.0-, 3.5-, and 4.5-mm screws were 79.5, 136.5, and 179.6 N, respectively. Average stiffness for each caliber was 14.8, 33.4, and 52.3 N/mm. CONCLUSIONS: Increasing screw diameter and IM fill resulted in more stable fixation, but marginal gains were seen in ratios >0.9. A minimum fill ratio of 0.74 was sufficient to withstand forces of early active motion with angular deformity <10°. CLINICAL RELEVANCE: An understanding of the relationship of IM fill ratio of metacarpal screws to fracture stability may provide a framework for clinicians to optimally size these implants.

Cytoplasmic binding partners of the Integrator endonuclease INTS11 and its paralog CPSF73 are required for their nuclear function.

INTS11 and CPSF73 are metal-dependent endonucleases for Integrator and pre-mRNA 3'-end processing, respectively. Here, we show that the INTS11 binding partner BRAT1/CG7044, a factor important for neuronal fitness, stabilizes INTS11 in the cytoplasm and is required for Integrator function in the nucleus. Loss of BRAT1 in neural organoids leads to transcriptomic disruption and precocious expression of neurogenesis-driving transcription factors. The structures of the human INTS9-INTS11-BRAT1 and Drosophila dIntS11-CG7044 complexes reveal that the conserved C terminus of BRAT1/CG7044 is captured in the active site of INTS11, with a cysteine residue directly coordinating the metal ions. Inspired by these observations, we find that UBE3D is a binding partner for CPSF73, and UBE3D likely also uses a conserved cysteine residue to directly coordinate the active site metal ions. Our studies have revealed binding partners for INTS11 and CPSF73 that behave like cytoplasmic chaperones with a conserved impact on the nuclear functions of these enzymes.

Outcomes Following a False-Positive Multi-Cancer Early Detection Test: Results from DETECT-A, the First Large, Prospective, Interventional MCED Study.

Guideline recommended standard of care screening is available for four cancer types; most cancer-related deaths are caused by cancers without standard of care screening. DETECT-A is the first prospective interventional trial evaluating a multi-cancer early detection (MCED) blood test (CancerSEEK) in women without a history of cancer, providing the first opportunity to assess the long-term outcomes of individuals with false-positive (FP) MCED results. This prospective analysis of DETECT-A participants with FP results evaluates the performance of an imaging-based diagnostic workflow and examines cancer risk following a FP result. This analysis included all DETECT-A participants with a positive CancerSEEK test and subsequent flourine-18 fluorodeoxyglucose positron emission tomography-IV contrast-enhanced computed tomography (18-F-FDG PET-CT) imaging and clinical workup indicating no evidence of cancer within 1 year of enrollment (n = 98). Medical records, study interactions, and study surveys were used to assess cancer incidence, treatments, and clinical outcomes through August 2023. Ninety-five of 98 participants with a FP result remained cancer-free with a median follow-up of 3.6 years (IQR: 2.5-4.1) from determination of FP status. Three incident cancers were observed over the follow-up period. One bilateral stage IIIC ovarian cancer was diagnosed 1.9 years after determination of FP status; two stage I breast cancers were diagnosed 0.1 and 1.6 years from determination of FP status. The annual incidence rate of cancer during follow-up from FP determination was 1.0% (95% confidence interval, 0.2%-2.8%). Participants with a positive CancerSEEK test who underwent 18-F-FDG PET-CT and clinical workup without cancer findings had low risk for cancer over the following several years. Prevention Relevance: This study provides multiyear clinical outcomes data following a false-positive multi-cancer early detection test for individuals participating in a prospective interventional trial. It provides a preliminary performance assessment of an imaging-based diagnostic workflow following a false-positive multi-cancer early detection test.

A preoperative risk assessment tool for predicting adverse outcomes among total shoulder arthroplasty patients.

BACKGROUND: With the increased utilization of Total Shoulder Arthroplasty (TSA) in the outpatient setting, understanding the risk factors associated with complications and hospital readmissions becomes a more significant consideration. Prior developed assessment metrics in the literature either consisted of hard-to-implement tools or relied on postoperative data to guide decision-making. This study aimed to develop a preoperative risk assessment tool to help predict the risk of hospital readmission and other postoperative adverse outcomes. METHODS: We retrospectively evaluated the 2019-2022(Q2) Medicare fee-for-service inpatient and outpatient claims data to identify primary anatomic or reserve TSAs and to predict postoperative adverse outcomes within 90 days postdischarge, including all-cause hospital readmissions, postoperative complications, emergency room visits, and mortality. We screened 108 candidate predictors, including demographics, social determinants of health, TSA indications, prior 12-month hospital, and skilled nursing home admissions, comorbidities measured by hierarchical conditional categories, and prior orthopedic device-related complications. We used two approaches to reduce the number of predictors based on 80% of the data: 1) the Least Absolute Shrinkage and Selection Operator logistic regression and 2) the machine-learning-based cross-validation approach, with the resulting predictor sets being assessed in the remaining 20% of the data. A scoring system was created based on the final regression models' coefficients, and score cutoff points were determined for low, medium, and high-risk patients. RESULTS: A total of 208,634 TSA cases were included. There was a 6.8% hospital readmission rate with 11.2% of cases having at least one postoperative adverse outcome. Fifteen covariates were identified for predicting hospital readmission with the area under the curve of 0.70, and 16 were selected to predict any adverse postoperative outcome (area under the curve = 0.75). The Least Absolute Shrinkage and Selection Operator and machine learning approaches had similar performance. Advanced age and a history of fracture due to orthopedic devices are among the top predictors of hospital readmissions and other adverse outcomes. The score range for hospital readmission and an adverse postoperative outcome was 0 to 48 and 0 to 79, respectively. The cutoff points for the low, medium, and high-risk categories are 0-9, 10-14, ≥15 for hospital readmissions, and 0-11, 12-16, ≥17 for the composite outcome. CONCLUSION: Based on Medicare fee-for-service claims data, this study presents a preoperative risk stratification tool to assess hospital readmission or adverse surgical outcomes following TSA. Further investigation is warranted to validate these tools in a variety of diverse demographic settings and improve their predictive performance.

The surgical treatment of proximal humerus fractures 2010-2019: United States national case volume and incidence trends.

Background: Proximal humerus fractures are the third most common fracture type for patients between the ages of 65 and 89 and occur more frequently in women than men. Given the variety of surgical treatments for proximal humerus fractures, the aim of this study was to (1) report United States national volume and incidence estimates for surgical management of proximal humerus fractures to better understand the changing practice over the past decade and (2) to analyze differences in volume and incidence among age groups, sex, and geographic region. Methods: Using IBM Marketscan national database, all patients that underwent open reduction internal fixation (ORIF), hemiarthroplasty, or reverse total shoulder arthroplasty (RTSA) between 2010 and 2019 were identified with Current Procedural Terminology codes. The dataset was further stratified to identify patients treated for proximal humerus fractures. IBM Marketscan provided discharge weights that were used to determine estimated national annual volumes of each procedure in IBM SPSS Statistics software (IBM Corp., Armonk, NY, USA). Volume and incidence were adjusted per 1,000,000 persons and calculated for subgroups according to age group, sex, and geographical region. The United States Census Bureau annual population data was used for all incidence calculations. Results: Over the past decade, the total volume and incidence of surgically treated proximal humerus fractures increased by 13% and 5%, respectively. Although overall incidence decreased, ORIF remained the most common surgical treatment. The greatest decrease in volume and incidence of ORIF occurred in patients ≥75. The incidence of ORIF treatment increased in the South and West while it decreased in the Northeast and Midwest. Total volume and incidence of HA decreased between 2010 and 2019 and this trend remained among all subgroups. Total volume and incidence of RTSA increased by over 300%. The incidence of males and females receiving RTSA increased by 266% and 320%, respectively. Volume and incidence of RTSA increased across all age groups. Volume and incidence of RTSA increased in the Midwest, South, and Western regions while it remained unchanged in the Northeast. Conclusion: Surgical management trends of proximal humerus fractures have changed greatly over the past decade. ORIF remains the most common surgical treatment for proximal humerus fractures. HA has fallen out of favor while RTSA has seen significant increases in usage across sex, age groups, and geographic regions. These trends represent a change in practice for treating proximal humerus fractures by considering all patient and fracture characteristics when opting for surgical management.

Outcomes following a false positive multi-cancer early detection (MCED) test: Results from DETECT-A, the first large, prospective, interventional MCED study.

Guideline recommended standard of care (SoC) screening is available for four cancer types; most cancer-related deaths are caused by cancers without SoC screening. DETECT-A is the first prospective interventional trial evaluating an MCED blood test (CancerSEEK) in women without a history of cancer, providing the first opportunity to assess the long-term outcomes of individuals with false positive (FP) MCED results. This prospective analysis of DETECT-A participants with FP results evaluates the performance of an imaging-based diagnostic workflow and examines cancer risk following a FP result. This analysis included all DETECT-A participants with a positive CancerSEEK test and subsequent flourine-18 fluorodeoxyglucose positron emission tomography-IV contrast enhanced computed tomography (18-F-FDG PET-CT) imaging and clinical workup indicating no evidence of cancer within one year of enrollment (n=98). Medical records, study interactions, and study surveys were used to assess cancer incidence, treatments, and clinical outcomes through August 2023. Ninety-five of 98 participants with a FP result remained cancer-free with a median follow-up of 3.6 years (IQR: 2.5-4.1) from determination of FP status. Three incident cancers were observed over the follow-up period. One bilateral stage IIIC ovarian cancer was diagnosed 1.9 years after determination of FP status; two stage I breast cancers were diagnosed 0.1 and 1.6 years from determination of FP status. The annual incidence rate of cancer during follow-up from FP determination was 1.0% (95% CI: 0.2%-2.8%). Participants with a positive CancerSEEK test who underwent 18-F-FDG PET-CT and clinical workup without cancer findings had low risk for cancer over the following several years.

Multiyear Clinical Outcomes of Cancers Diagnosed Following Detection by a Blood-Based Multicancer Early Detection Test.

In the US, <20% of cancers are diagnosed by standard-of-care (SoC) screening. Multicancer early detection (MCED) tests offer the opportunity to expand cancer screening. Understanding the characteristics and clinical outcomes of MCED-detected cancers is critical to clarifying MCED tests' potential impact. DETECT-A is the first prospective interventional trial of an MCED blood test (CancerSEEK). CancerSEEK, coupled with diagnostic PET-CT, identified cancers including those not detected by SoC screening, the majority of which were localized or regional. We report multiyear outcomes in patients with cancers diagnosed following a positive CancerSEEK test. Nine cancer types were diagnosed in 26 participants whose cancers were first detected by CancerSEEK. Information on cancer diagnoses, treatments, and clinical outcomes was extracted from medical records through November 2022. Data collection occurred at a median of 4.4 years (IQR: 4.1-4.6) following study enrollment. Thirteen of 26 (50%) participants were alive and cancer-free [ovarian (4), thyroid (1), uterine (2), breast (1), colorectal (2), and lung (3)]; 7/13 (54%) had cancers without recommended SoC screening modalities. All eight treated stage I or II participants (8/8, 100%) and 12/14 (86%) surgically treated participants were alive and cancer-free. Eligibility for surgical treatment was associated with favorable multiyear outcomes (P = 0.0002). Half of participants with MCED-detected cancers were alive and cancer-free after 4.4 years median follow-up. Most were diagnosed with early-stage cancers and were treated surgically. These results suggest that early cancer detection by CancerSEEK may have facilitated curative-intent treatments and associated positive clinical outcomes in some DETECT-A participants. Prevention Relevance: This study provides preliminary evidence of the potential of multicancer early detection testing as an effective screening tool for detecting cancers without standard-of-care (SoC) screening modalities and complementing SoC cancer screening.

A UL26-PIAS1 complex antagonizes anti-viral gene expression during Human Cytomegalovirus infection.

Viral disruption of innate immune signaling is a critical determinant of productive infection. The Human Cytomegalovirus (HCMV) UL26 protein prevents anti-viral gene expression during infection, yet the mechanisms involved are unclear. We used TurboID-driven proximity proteomics to identify putative UL26 interacting proteins during infection to address this issue. We find that UL26 forms a complex with several immuno-regulatory proteins, including several STAT family members and various PIAS proteins, a family of E3 SUMO ligases. Our results indicate that UL26 prevents STAT phosphorylation during infection and antagonizes transcriptional activation induced by either interferon α (IFNA) or tumor necrosis factor α (TNFα). Additionally, we find that the inactivation of PIAS1 sensitizes cells to inflammatory stimulation, resulting in an anti-viral transcriptional environment similar to ΔUL26 infection. Further, PIAS1 is important for HCMV cell-to-cell spread, which depends on the presence of UL26, suggesting that the UL26-PIAS1 interaction is vital for modulating intrinsic anti-viral defense.

Five-Year Mortality Rates Following Elective Shoulder Arthroplasty and Shoulder Arthroplasty for Fracture in Patients Over Age 65.

Background: To effectively counsel patients prior to shoulder arthroplasty, surgeons should understand the overall life trajectory and life expectancy of patients in the context of the patient's shoulder pathology and medical comorbidities. Such an understanding can influence both operative and nonoperative decision-making and implant choices. This study evaluated 5-year mortality following shoulder arthroplasty in patients ≥65 years old and identified associated risk factors. Methods: We utilized Centers for Medicare & Medicaid Services Fee-for-Service inpatient and outpatient claims data to investigate the 5-year mortality rate following shoulder arthroplasty procedures performed from 2014 to 2016. The impact of patient demographics, including fracture diagnosis, year fixed effects, and state fixed effects; patient comorbidities; and hospital-level characteristics on 5-year mortality rates were assessed with use of a Cox proportional hazards regression model. A p value of <0.05 was considered significant. Results: A total of 108,667 shoulder arthroplasty cases (96,104 nonfracture and 12,563 fracture) were examined. The cohort was 62.7% female and 5.8% non-White and had a mean age at surgery of 74.3 years. The mean 5-year mortality rate was 16.6% across all shoulder arthroplasty cases, 14.9% for nonfracture cases, and 29.9% for fracture cases. The trend toward higher mortality in the fracture group compared with the nonfracture group was sustained throughout the 5-year postoperative period, with a fracture diagnosis being associated with a hazard ratio of 1.63 for mortality (p < 0.001). Medical comorbidities were associated with an increased risk of mortality, with liver disease bearing the highest hazard ratio (3.07; p < 0.001), followed by chronic kidney disease (2.59; p < 0.001), chronic obstructive pulmonary disease (1.92; p < 0.001), and congestive heart failure (1.90; p < 0.001). Conclusions: The mean 5-year mortality following shoulder arthroplasty was 16.6%. Patients with a fracture diagnosis had a significantly higher 5-year mortality risk (29.9%) than those with a nonfracture diagnosis (14.9%). Medical comorbidities had the greatest impact on mortality risk, with chronic liver and kidney disease being the most noteworthy. This novel longer-term data can help with patient education and risk stratification prior to undergoing shoulder replacement. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Regulation of the Drosophila transcriptome by Pumilio and the CCR4-NOT deadenylase complex.

The sequence-specific RNA-binding protein Pumilio (Pum) controls Drosophila development; however, the network of mRNAs that it regulates remains incompletely characterized. In this study, we use knockdown and knockout approaches coupled with RNA-seq to measure the impact of Pum on the transcriptome of Drosophila cells in culture. We also use an improved RNA coimmunoprecipitation method to identify Pum-bound mRNAs in Drosophila embryos. Integration of these data sets with the locations of Pum-binding motifs across the transcriptome reveals novel direct Pum target genes involved in neural, muscle, wing, and germ cell development and in cellular proliferation. These genes include components of Wnt, TGF-ß, MAPK/ERK, and Notch signaling pathways, DNA replication, and lipid metabolism. We identify the mRNAs regulated by the CCR4-NOT deadenylase complex, a key factor in Pum-mediated repression, and observe concordant regulation of Pum:CCR4-NOT target mRNAs. Computational modeling reveals that Pum binding, binding site number, clustering, and sequence context are important determinants of regulation. In contrast, we show that the responses of direct mRNA targets to Pum-mediated repression are not influenced by the content of optimal synonymous codons. Moreover, contrary to a prevailing model, we do not detect a role for CCR4-NOT in the degradation of mRNAs with low codon optimality. Together, the results of this work provide new insights into the Pum regulatory network and mechanisms and the parameters that influence the efficacy of Pum-mediated regulation.

A fearful scourge to the penguin colonies: Southern giant petrel (Macronectes giganteus) predation on living Magellanic penguins (Spheniscus magellanicus) may be more common than assumed.

Southern giant petrels (Macronectes giganteus) are important consumers that range across the oceans throughout the southern hemisphere. In Argentina, previous studies have shown they eat primarily pinnipeds and penguins, which they are assumed to scavenge, although there are occasional anecdotes of them attacking living penguins. Here we describe a predation attempt by a trio of southern giant petrels on a molting adult Magellanic penguin (Spheniscus magellanicus) at the large colony at Punta Tombo, Argentina. We relate giant petrel attendance patterns at the colony to the penguins' phenology, showing how giant petrel numbers rise with the increasing prevalence of vulnerable penguins. We suggest that living penguins-both fledglings and adults-may constitute a more seasonally significant proportion of the giant petrel diet than previously assumed, and their capture may represent a specialized predation technique.

Real-time evaluation and adaptation to facilitate rapid recruitment in a large, prospective cohort study.

BACKGROUND: Recruiting large cohorts efficiently can speed the translation of findings into care across a range of scientific disciplines and medical specialties. Recruitment can be hampered by factors such as financial barriers, logistical concerns, and lack of resources for patients and clinicians. These and other challenges can lead to underrepresentation in groups such as rural residents and racial and ethnic minorities. Here we discuss the implementation of various recruitment strategies for enrolling participants into a large, prospective cohort study, assessing the need for adaptations and making them in real-time, while maintaining high adherence to the protocol and high participant satisfaction. METHODS: While conducting a large, prospective trial of a multi-cancer early detection blood test at Geisinger, an integrated health system in central Pennsylvania, we monitored recruitment progress, adherence to the protocol, and participants' satisfaction. Tracking mechanisms such as paper records, electronic health records, research databases, dashboards, and electronic files were utilized to measure each outcome. We then reviewed study procedures and timelines to list the implementation strategies that were used to address barriers to recruitment, protocol adherence and participant satisfaction. RESULTS: Adaptations to methods that contributed to achieving the enrollment goal included offering multiple recruitment options, adopting group consenting, improving visit convenience, increasing the use of electronic capture and the tracking of data and source documents, staffing optimization via leveraging resources external to the study team when appropriate, and integrating the disclosure of study results into routine clinical care without adding unfunded work for clinicians. We maintained high protocol adherence and positive participant experience as exhibited by a very low rate of protocol deviations and participant complaints. CONCLUSION: Recruiting rapidly for large studies - and thereby facilitating clinical translation - requires a nimble, creative approach that marshals available resources and changes course according to data. Planning a rigorous assessment of a study's implementation outcomes prior to study recruitment can further ground study adaptations and facilitate translation into practice. This can be accomplished by proactively and continuously assessing and revising implementation strategies.

Methylprednisolone taper is an effective addition to multimodal pain regimens after total shoulder arthroplasty: results of a randomized controlled trial: 2022 Neer Award winner.

BACKGROUND: Perioperative corticosteroids have shown potential as nonopioid analgesic adjuncts for various orthopedic pathologies, but there is a lack of research on their use in the postoperative setting after total shoulder arthroplasty (TSA). The purpose of this study was to assess the effect of a methylprednisolone taper on a multimodal pain regimen after TSA. METHODS: This study was a randomized controlled trial (clinicaltrials.gov NCT03661645) of opioid-naive patients undergoing TSA. Patients were randomly assigned to receive intraoperative dexamethasone only (control group) or intraoperative dexamethasone followed by a 6-day oral methylprednisolone (Medrol) taper course (treatment group). All patients received the same standardized perioperative pain management protocol. Standardized pain journal entries were used to record visual analog pain scores (VAS-pain), VAS-nausea scores, and quantity of opioid tablet consumption during the first 7 postoperative days (POD). Patients were followed for at least one year postoperatively for clinical evaluation, collection of patient-reported outcomes, and observation of complications. RESULTS: A total of 67 patients were enrolled in the study; 32 in the control group and 35 in the treatment group. The groups had similar demographics and comorbidities. The treatment group demonstrated a reduction in mean VAS pain scores over the first 7 POD. Between POD 1 and POD 7, patients in the control group consumed an average of 17.6 oxycodone tablets while those in the treatment group consumed an average of 5.5 tablets. This equated to oral morphine equivalents of 132.1 and 41.1 for the control and treatment groups, respectively. There were fewer opioid-related side effects during the first postoperative week in the treatment group. The treatment group reported improved VAS pain scores at 2-week, 6-week, and 12-week postoperatively. There were no differences in Europe Quality of Life, shoulder subjective value (SSV), at any time point between groups, although American Shoulder and Elbow Surgeons questionnaire scores showed a slight improvement at 6-weeks in the treatment group. At mean follow-up, (control group: 23.4 months; treatment group:19.4 months), there was 1 infection in the control group and 1 postoperative cubital tunnel syndrome in the treatment group. No other complications were reported. CONCLUSIONS: A methylprednisolone taper course shows promise in reducing acute pain and opioid consumption as part of a multimodal regimen following TSA. As a result of this study, we have included this 6-day methylprednisolone taper course in our multimodal regimen for all primary shoulder arthroplasties. We hope this trial serves as a foundation for future studies on the use of low-dose oral corticosteroids and other nonnarcotic modalities to control pain after shoulder surgeries.

PolyAMiner-Bulk is a deep learning-based algorithm that decodes alternative polyadenylation dynamics from bulk RNA-seq data.

Alternative polyadenylation (APA) is a key post-transcriptional regulatory mechanism; yet, its regulation and impact on human diseases remain understudied. Existing bulk RNA sequencing (RNA-seq)-based APA methods predominantly rely on predefined annotations, severely impacting their ability to decode novel tissue- and disease-specific APA changes. Furthermore, they only account for the most proximal and distal cleavage and polyadenylation sites (C/PASs). Deconvoluting overlapping C/PASs and the inherent noisy 3' UTR coverage in bulk RNA-seq data pose additional challenges. To overcome these limitations, we introduce PolyAMiner-Bulk, an attention-based deep learning algorithm that accurately recapitulates C/PAS sequence grammar, resolves overlapping C/PASs, captures non-proximal-to-distal APA changes, and generates visualizations to illustrate APA dynamics. Evaluation on multiple datasets strongly evinces the performance merit of PolyAMiner-Bulk, accurately identifying more APA changes compared with other methods. With the growing importance of APA and the abundance of bulk RNA-seq data, PolyAMiner-Bulk establishes a robust paradigm of APA analysis.

Mixed-reality improves execution of templated glenoid component positioning in shoulder arthroplasty: a CT imaging analysis.

INTRODUCTION: Glenoid placement is critical for successful outcomes in total shoulder arthroplasty (TSA). Preoperative templating with three-dimensional imaging has improved implant positioning, but deviations from the planned inclination and version still occur. Mixed-Reality (MR) is a novel technology that allows surgeons intra-operative access to three-dimensional imaging and templates, capable of overlaying the surgical field to help guide component positioning. The purpose of this study was to compare the execution of preoperative templates using MR vs.standard instruments (SIs). METHODS: Retrospective review of 97 total shoulder arthroplasties (18 anatomic, 79 reverse) from a single high-volume shoulder surgeon between January 2021 and February 2023, including only primary diagnoses of osteoarthritis, rotator cuff arthropathy, or a massive irreparable rotator cuff tear. To be included, patients needed a templated preoperative plan and then a postoperative computed tomography scan. Allocation to MR vs. SI was based on availability of the MR headset, industry technical personnel, and the templated preoperative plan loaded into the software, but preoperative or intraoperative patient factors did not contribute to the allocation decision. Postoperative inclination and version were measured by two independent, blinded physicians and compared to the preoperative template. From these measurements, we calculated the mean difference, standard deviation (SD), and variance to compare MR and SI. RESULTS: Comparing 25 MR to 72 SI cases, MR significantly improved both inclination (P < .001) and version (P < .001). Specifically, MR improved the mean difference from preoperative templates (by 1.9° inclination, 2.4° version), narrowed the SD (by 1.7° inclination, 1.8° version), and decreased the variance (11.7-3.0 inclination, 14.9-4.3 version). A scatterplot of the data demonstrates a concentration of MR cases within 5° of plan relative to SI cases typically within 10° of plan. There was no difference in operative time. CONCLUSION: MR improved the accuracy and precision of glenoid positioning. Although it is unlikely that 2° makes a detectable clinical difference, our results demonstrate the potential ability for technology like MR to narrow the bell curve and decrease the outliers in glenoid placement. This will be particularly relevant as MR and other similar technologies continue to evolve into more effective methods in guiding surgical execution.

The Top 100 Classical and Contemporary Papers on Elbow Surgery: A Trend Analysis of Elbow Surgery Literature.

INTRODUCTION: Bibliometric analyses provide an aggregate of the most frequently cited literature in a given field. The purpose of this study was to analyze the top 100 most-cited classical and contemporary papers relating to elbow surgery to serve as a reference for surgeons and trainees for educational and research purposes. METHODS: A search was conducted for all papers containing the term "elbow" in the categories Orthopedics, Surgery, and Sports Science in the Clarivate Web of Science. Classical papers were those published from 1980 to 2009, and contemporary papers were those published from 2010 to 2019. Articles were assessed by country of origin, authors and their credentials, parent journal, level of evidence, and topic. RESULTS: Citation frequency ranged from 86 to 867. Among the classical group, there were more level IV papers compared with level I papers; however, the opposite was true in the contemporary group. The most common topic in the classical group was elbow anatomy and function, and the most common topic in the contemporary group was lateral epicondylitis and medial epicondylitis and associated therapies. DISCUSSION: This bibliometric analysis serves to help guide surgeons and trainees on the highly cited articles and important topics in elbow surgery, demonstrating a shift to prospective randomized controlled trials in recent years. LEVEL OF EVIDENCE: Level V (Systematic Review with Level V as Lowest LOE).