Evolution of Reverse Shoulder Arthroplasty Design Rationales and Where We Are Now.

Reverse shoulder arthroplasty (RSA) will soon reach its 20-year anniversary in the United States and has now become the most performed shoulder arthroplasty in the United States. The evolution from Grammont style implants to lateralized designs continues to generate debate as comparable outcomes have been reported with both types of systems. While early literature focused on fixation and expanded indications, recent studies have evaluated component design and position and their effect on functional outcomes and complications. The purpose of this article was to provide a synopsis of design rationales of current RSA prostheses and review outcomes related to RSA design and position.

Anatomic variations of the deltoid muscle insertion: a cadaveric study.

Background: The deltoid is a trisegmented muscle with anterior, middle, and posterior components. While the clinical relevance of the presence of anatomic variations of the deltoid origin and insertion continues to be debated, the architecture of the deltoid muscle is more complex than initially believed. This study aimed to evaluate the gross anatomy of the deltoid muscle insertion by qualitatively and quantitatively characterizing the insertion and location of the deltoid muscle's anterior, middle, and posterior components. This information is valuable to surgeons as it raises awareness of potential variants that could be encountered during surgery, promotes mindfulness of neurovascular proximities, and reduces the likelihood of confusion between adjacent muscle fibers. Methods: Eight nonpaired, fresh-frozen clavicle-to-fingertip cadaveric shoulders were acquired for the study (6 left, 2 right). The average age of the cadavers was 79.5 years (range: 64-92). The standard deltopectoral approach was carried out on all specimens. The planes dividing the anterior, middle, and posterior deltoid were identified and marked. Once complete exposure had been achieved, digital calipers were used to record the size of the deltoid insertion. The specimens were qualitatively assessed to characterize the style of insertion they demonstrated. Results: The average length of the deltoid insertion was 39.45 ± 9.33 mm (n = 8). Six of the eight shoulders demonstrated an insertion style previously characterized in the literature. The remaining two shoulders highlighted an insertion pattern not previously described. Conclusion: The current study demonstrates a novel insertion pattern for the deltoid muscle that has not been previously characterized. This "step-off" insertion pattern shows that the anterior, middle, and posterior tendons are inserted superior-medial, directly on, and inferior-lateral to the deltoid tuberosity and was found in 2/8 of our cadaveric specimens.

Dermal Allograft Augmentation for Large and Massive Rotator Cuff Tears and Revisions: A Case Series.

Introduction Arthroscopic advancements have notably improved rotator cuff repair, yet the healing of tendons and retear risks still pose significant challenges, especially with massive and large tears. These larger tears have shown a quadruple increase in retear rate when the tear size grows from 1-3 cm. The prevalent cause of failure, particularly in tears with fatty degeneration, is suture tearing. As such, techniques that enhance tendon healing are pivotal due to their correlation with improved functional outcomes. Dermal allograft augmentation (DAA) is one method that has demonstrated improvements in rotator cuff repair biomechanics, as well as the promotion of vascularization and neotendon formation. This study evaluates the efficacy of DAA in the postoperative healing of large and massive rotator cuff tears, assessed through patient-reported outcomes and functional range of motion. Methods This retrospective study reviewed a single surgeon's database, selecting patients who underwent arthroscopic surgery for full-thickness rotator cuff tears measuring at least 3 cm, or those with maximum stage II fatty infiltration of the supraspinatus or infraspinatus muscle on MRI. We used three validated patient-reported outcome (PRO) measures, American Shoulder and Elbow Surgeon Score (ASES), Single Assessment Numeric Evaluation (SANE), and Simple Shoulder Test (SST), alongside a range of motion metrics, external rotation (ER), and forward flexion (FF). These were recorded pre-operatively and, at minimum, one year post-operatively, with a standard student t-test employed for comparative analysis. Results Out of 18 total patients, the average age was 61 years, and 83% were male. The cause of injury was mostly traumatic in nature (n=11), with the remainder being chronic (n=7). All three PROs (n=11) demonstrated a statistically significant increase in score including ASES (p=0.003), SANE (p=0.004), and SST (p=0.039). External rotation also significantly improved pre- to post-operative function (46 vs 58, p=0.049). Three patients (17%) suffered from a retear within three months of their rotator cuff repair. Two patients (11%) required a reverse shoulder arthroplasty within a year. Conclusion Our study demonstrated that DAA in rotator cuff repair yielded notable functional and clinical advancements, with a moderately low retear rate as confirmed by ultrasound. These outcomes suggest that DAA is a promising intervention for large and historically difficult rotator cuff tears, offering significant implications for future treatment protocols.

Obesity is associated with improvement in functional outcome but lower internal rotation after reverse shoulder arthroplasty.

Background: The role of obesity as an independent risk factor for increased complications following reverse shoulder arthroplasty (RSA) continues to generate debate. While no standardized body mass index (BMI) cutoff values for shoulder arthroplasty exist, many surgeons are concerned about the potential for poor outcomes and decreased range of motion (ROM) in patients with a high BMI. The purpose of this study was to compare functional outcomes in obese and nonobese patients preoperatively and at short-term follow-up after RSA. Methods: A retrospective review was performed of a prospectively maintained, multicenter database of primary RSAs performed by 14 surgeons between 2015 and 2019 with minimum 2-year follow-up. A total of 245 patients met the study criteria, including 111 obese (BMI >30) and 134 nonobese (BMI <30) patients. Patient-reported outcomes (PROs) as well as ROM measurements were compared between the 2 groups. Results: At baseline, obese patients had significantly lower American Shoulder and Elbow Surgeons (36.6 vs. 42.0, P = .014), Western Ontario Osteoarthritis of the Shoulder scores (33.1 vs. 37.8, P = .043), external rotation at 90° (19° vs. 28°, P = .007), internal rotation (IR) spinal level (L5 vs. L4, P = .002), and belly press strength (P = .003) compared to the nonobese cohort. There were no statistical differences in 2-year outcomes (PROs, ROM, and strength) other than a worse IR (spinal level) in the low BMI group (L4 vs. L3, P = .002). In linear regression analyses controlling for confounding variables, increasing BMI was negatively correlated with preoperative external rotation (B = -0.591, P = .034) and preoperative IR spinal level (B = 0.089, P = .002). Increasing BMI was not correlated with postoperative external rotation at 90° (B = 0.189, P = .490) but was associated with worse postoperative IR by spinal level (B = 0.066, P = .043). Conclusions: Obese patients have greater restrictions in external and internal rotation as well as American Shoulder and Elbow Surgeons and Western Ontario Osteoarthritis of the Shoulder scores at baseline prior to RSA. However, there are no major differences in postoperative PROs or ROM measurements between obese and nonobese patients apart from a worse active IR by spinal level in the obese group (L4 vs. L3, P = .002). This study suggests that an RSA procedure does not need to be restricted solely based on BMI.

Stener-like lesion of the lateral meniscus in the setting of a multiligamentous knee injury: A case report.

Traumatic dislocations of the knee can result in significant soft tissue damage including multiligamentous and meniscal knee injury. When a meniscal tear involves the posterior horn, the meniscus loses one of its attachments to the tibia and can become extruded from the joint. Stener-like lesions of the knee have been reported throughout the literature; however, they have been exclusively described as a distal tear of the medial collateral ligament (MCL) lying superficial to the pes anserine tendon which prevents anatomic healing. The purpose of this report is to present a previously unreported unique variant of a lateral meniscus tear in the setting of a MLKI. In this case presentation, the lateral meniscus became extruded superficial to the intact lateral collateral ligament (LCL) resulting in a Stener-like lesion. Corrective recognition of lesions like these and timely surgical intervention is recommended to restore native anatomy and prevent chronic pain, instability, and premature degenerative disease. Level IV, Case report.

Return-to-Golf Rate After Shoulder Arthroplasty: A Systematic Review and Meta-analysis.

Background: With advancements in the technology, techniques, and biomechanical understanding of shoulder arthroplasty, higher rates of postoperative return to various sports have been seen in the past decade. Purpose: To observe the return-to-golf rate after various types of shoulder arthroplasty (anatomic total shoulder arthroplasty [TSA], hemiarthroplasty [HA], and reverse total shoulder arthroplasty [RSA]) and also to review the protocols for return to golf. Study Design: Scoping review; Level of evidence, 4. Methods: The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed in a search of PubMed, JSTOR, Google Scholar, ScienceDirect, and CORE using the keywords "return to sport,""shoulder arthroplasty,""golf,""TSA,""shoulder arthroplasty,""hemiarthroplasty,""reverse shoulder arthroplasty,""RSA,""sports," and "athlete." Of 145 preliminary results, 10 retrospective studies (n = 178 patients) published between 1998 and 2021 were included in the final analysis. Results: The mean patient age was 65 years. Of the 172 patients with reported return-to-sport rates, the mean return-to-golf rate was 75.8% for all types of shoulder arthroplasty. Of these 172 patients, 107 patients were categorized by type of procedure: Anatomic TSA had the highest return-to-golf rate at 77.6% (49/107), followed by HA at 64.3% (14/107) and RSA at 59.1% (44/107). Four studies commented on return to the full 18 holes of golf, with a return-to-sport timeline ranging from 5 to 6 months postoperatively. One study specified the return-to-golf timeline based on the type of shot and reported the mean number of weeks before putting, chipping, and returning to the course as 20, 22, and 27 weeks, respectively. Two studies that reported on golf playing frequency noted an increase from before to 1 year after TSA, from a mean of 1.6 and 0.7 times per week to 2.0 and 1.7 times per week, respectively. Only 1 study, published in 1998, provided a comprehensive return-to-golf protocol. Conclusion: The return-to-golf rate after shoulder arthroplasty was highest after anatomic TSA (78%) compared with HA (64%) and RSA (59%). The most commonly reported duration before returning to a full 18 holes was 5 to 6 months, but patients returned to putting and chipping earlier.

Acute exercise-induced release of innate immune proteins via small extracellular vesicles changes with aerobic fitness and age.

AIM: Physical exercise triggers the secretion of small extracellular vesicles (sEVs) into the circulation in humans, enabling signalling crosstalk between tissues. Exercise-derived EVs and their cargo have been proposed to mediate adaptations to exercise; however, our understanding of how exercise-derived EV protein cargo is modulated by factors such as aerobic fitness and age of an individual is currently unknown. Here, we examined the circulating sEV proteome following aerobic exercise in healthy males of different ages and aerobic fitness to understand exercise-induced EV response during the aging process. METHODS: Twenty-eight healthy men completed a bout of 20-min cycling exercise at 70% estimated VO2peak . Small EVs were isolated from blood samples collected before and immediately after exercise, and then quantified using particle analysis and Western blotting. Small EV proteome was examined using quantitative proteomic analysis. RESULTS: We identified a significant increase in 13 proteins in small plasma EVs following moderate-to-vigorous intensity exercise. We observed distinct changes in sEV proteome after exercise in young, mature, unfit, and fit individuals, highlighting the impact of aerobic fitness and age on sEV protein secretion. Functional enrichment and pathway analysis identified that the majority of the significantly altered sEV proteins are associated with the innate immune system, including proteins known to be damage-associated molecular patterns (DAMPs). CONCLUSION: Together, our findings suggest that exercise-evoked acute stress can positively challenge the innate immune system through the release of signalling molecules such as DAMPs in sEVs, proposing a novel EV-based mechanism for moderate-to-vigorous intensity exercise in immune surveillance pathways.

Using a Multi-pronged Behavioral Intervention to Standardize Antibiotic Prophylaxis at the Time of Foley Catheter Removal After Radical Prostatectomy.

OBJECTIVE: To identify antibiotic prescribing patterns at the time of foley catheter removal after radical prostatectomy and implement a multi-pronged behavioral intervention to standardize antibiotic use. METHODS: This was a single-institution study examining the prescribing of antibiotics at the time of foley catheter removal after radical prostatectomy. Pre-intervention data were collected retrospectively to establish baselines for antibiotic prescribing, patient characteristics, and urinary tract infection rates. A single dose of an oral antibiotic taken at the time of foley catheter removal was recommended as the standard antibiotic protocol. A multi-pronged behavioral intervention was used to encourage compliance with our protocol. Adherence to the protocol, quantity of antibiotics prescribed, and rate of urinary tract infection were recorded prospectively. Durability of the intervention was evaluated during a post-intervention phase. RESULTS: A total of 416 patients and 6 surgeons were included in the study. Accordance with the standardized antibiotic protocol was 59% in the pre-intervention phase and 91% in the intervention phase (P = .03). No patients in the intervention or post-intervention phase were prescribed more than one dose of an antibiotic. The rate of urinary tract infection did not differ across the study phases. CONCLUSION: Implementation of a multi-pronged behavioral intervention resulted in a high rate of surgeon compliance with a standardized antibiotic protocol. This led to a significant reduction in antibiotic use with no change in the rate of urinary tract infection after foley catheter removal after radical prostatectomy.

Financial Implications of the Merit-Based Incentive Payment System for Surgical Health Care Professionals.

This study describes financial implications of the merit-based incentive payment system for surgical health care professionals.

Comparison of Radiation Exposure for Pregnant Patients Requiring Intervention for Suspected Obstructing Nephrolithiasis.

OBJECTIVE: To identify the differences in radiation exposure per suspected stone episode between percutaneous nephrostomy tube (PCN), stent, and primary ureteroscopy (URS).The incidence of nephrolithiasis in pregnancy is low; however, repercussions for both mother and fetus can be significant. In cases of suspected obstructing nephrolithiasis, intervention may be required, including ureteral stent, PCN, or URS, with the potential for multiple subsequent procedures that often utilize fluoroscopy. METHODS: Pregnant patients who required an intervention (stent, PCN, or URS) for suspected obstructing nephrolithiasis were retrospectively reviewed. The primary outcome was total fluoroscopy exposure per suspected stone episode. Secondary outcomes included fluoroscopic exposure per procedure and number of procedures required. RESULTS: After excluding patients with renal anomalies and incomplete radiation data, 78 out of 100 patients were included in the analysis. Forty patients (51.3%) underwent initial stent placement, 22 (28.2%) underwent initial PCN placement, and 16 (20.5%) underwent primary URS. Total mean radiation exposure per stone episode was significantly higher in patients who underwent PCN, (286.9 mGy vs 3.7 mGy (stent) and 0.2 mGy (URS), P <.001). In addition, patients who underwent initial PCN placement had significantly more procedures (P <.001) and mean radiation exposure per procedure was higher (P <.001). More than 40% of PCNs experienced dysfunction, and mean duration between PCN exchanges was 16.5 days. CONCLUSION: In pregnant patients with suspected obstructing nephrolithiasis requiring intervention, initial PCN placement was associated with a significantly higher number of procedures, radiation exposure per procedure, and total radiation exposure per suspected stone episode compared to stent and URS.

Anterior cruciate ligament reconstruction with a biocomposite interference screw maintains graft fixation survival and improves clinical outcomes at 1 year: A multicenter prospective case series.

A biocomposite interference screw with an open architecture was developed to provide a greater available surface area for bone ingrowth compared with conventional solid interference screws. We herein describe a prospective, single-cohort study conducted using this interference screw in anterior cruciate ligament (ACL) reconstruction. Sixty subjects (mean age, 34.9 years; standard deviation, 10.6) undergoing ACL repair using the biocomposite interference screw were enrolled at 3 sites in the United States. Subjects were followed preoperatively (baseline) and postoperatively at 6 months and 1 year. The primary endpoint was graft fixation survival rate at 6 months and 1 year. Secondary endpoints included graft survival (failure defined as that occurring for any reason); International Knee Documentation Committee (IKDC) score (exam and subjective forms); Tegner Activity form; Lysholm score; and EQ (EuroQuol)-5D-5L index score and visual analogue scale. There was a 100 % rate of graft fixation survival at 6 months (54/54; 95 % confidence interval [CI]: 100-100) and 1 year (50/50; 95 % CI: 100-100). One patient experienced a complete tear of the ACL 5 months following index surgery, resulting in graft survival rates of 98.1 % (53/54; 95 % CI: 94.6-100) at 6 months at 98.0 % (49/50; 95 % CI: 94.1-100) at 1 year. Significant improvements (p < .0001) were obtained between baseline and 6 months for the majority of patient-reported outcomes, and were maintained out to 1-year follow up. There was no significant difference over baseline in the IKDC sub-scale of symptoms. Nine patients (15.0 %) experienced serious adverse events during the course of the study; three of these patients' adverse events were considered possibly or definitely related to the procedure device (ACL tear, pulmonary embolism/deep vein thrombosis, and a patellar fracture). In conclusion, this biocomposite interference screw has a favorable safety and efficacy profile at 1 year, with no failures of graft fixation, noted during that time.

Sex differences in muscle protein expression and DNA methylation in response to exercise training.

BACKGROUND: Exercise training elicits changes in muscle physiology, epigenomics, transcriptomics, and proteomics, with males and females exhibiting differing physiological responses to exercise training. However, the molecular mechanisms contributing to the differing adaptations between the sexes are poorly understood. METHODS: We performed a meta-analysis for sex differences in skeletal muscle DNA methylation following an endurance training intervention (Gene SMART cohort and E-MTAB-11282 cohort). We investigated for sex differences in the skeletal muscle proteome following an endurance training intervention (Gene SMART cohort). Lastly, we investigated whether the methylome and proteome are associated with baseline cardiorespiratory fitness (maximal oxygen consumption; VO2max) in a sex-specific manner. RESULTS: Here, we investigated for the first time, DNA methylome and proteome sex differences in response to exercise training in human skeletal muscle (n = 78; 50 males, 28 females). We identified 92 DNA methylation sites (CpGs) associated with exercise training; however, no CpGs changed in a sex-dependent manner. In contrast, we identified 189 proteins that are differentially expressed between the sexes following training, with 82 proteins differentially expressed between the sexes at baseline. Proteins showing the most robust sex-specific response to exercise include SIRT3, MRPL41, and MBP. Irrespective of sex, cardiorespiratory fitness was associated with robust methylome changes (19,257 CpGs) and no proteomic changes. We did not observe sex differences in the association between cardiorespiratory fitness and the DNA methylome. Integrative multi-omic analysis identified sex-specific mitochondrial metabolism pathways associated with exercise responses. Lastly, exercise training and cardiorespiratory fitness shifted the DNA methylomes to be more similar between the sexes. CONCLUSIONS: We identified sex differences in protein expression changes, but not DNA methylation changes, following an endurance exercise training intervention; whereas we identified no sex differences in the DNA methylome or proteome response to lifelong training. Given the delicate interaction between sex and training as well as the limitations of the current study, more studies are required to elucidate whether there is a sex-specific training effect on the DNA methylome. We found that genes involved in mitochondrial metabolism pathways are differentially modulated between the sexes following endurance exercise training. These results shed light on sex differences in molecular adaptations to exercise training in skeletal muscle.

Methylome and proteome integration in human skeletal muscle uncover group and individual responses to high-intensity interval training.

Exercise is a major beneficial contributor to muscle metabolism, and health benefits acquired by exercise are a result of molecular shifts occurring across multiple molecular layers (i.e., epigenome, transcriptome, and proteome). Identifying robust, across-molecular level targets associated with exercise response, at both group and individual levels, is paramount to develop health guidelines and targeted health interventions. Sixteen, apparently healthy, moderately trained (VO2 max = 51.0 ± 10.6 mL min-1 kg-1 ) males (age range = 18-45 years) from the Gene SMART (Skeletal Muscle Adaptive Responses to Training) study completed a longitudinal study composed of 12-week high-intensity interval training (HIIT) intervention. Vastus lateralis muscle biopsies were collected at baseline and after 4, 8, and 12 weeks of HIIT. DNA methylation (~850 CpG sites) and proteomic (~3000 proteins) analyses were conducted at all time points. Mixed models were applied to estimate group and individual changes, and methylome and proteome integration was conducted using a holistic multilevel approach with the mixOmics package. A total of 461 proteins significantly changed over time (at 4, 8, and 12 weeks), whilst methylome overall shifted with training only one differentially methylated position (DMP) was significant (adj.p-value < .05). K-means analysis revealed cumulative protein changes by clusters of proteins that presented similar changes over time. Individual responses to training were observed in 101 proteins. Seven proteins had large effect-sizes >0.5, among them are two novel exercise-related proteins, LYRM7 and EPN1. Integration analysis showed bidirectional relationships between the methylome and proteome. We showed a significant influence of HIIT on the epigenome and more so on the proteome in human muscle, and uncovered groups of proteins clustering according to similar patterns across the exercise intervention. Individual responses to exercise were observed in the proteome with novel mitochondrial and metabolic proteins consistently changed across individuals. Future work is required to elucidate the role of these proteins in response to exercise.

Phospho-Analyst: An Interactive, Easy-to-Use Web Platform To Analyze Quantitative Phosphoproteomics Data.

Phosphoproteomics is nowadays the method of choice to comprehensively identify and quantify thousands of phosphorylated peptides and their associated proteins with the goal of interrogating changes in signal transduction pathways and other cellular processes. One of the most popular software suites to analyze phosphoproteomic data sets is MaxQuant, which converts mass spectrometric raw data into quantitative information on phosphopeptides and proteins. However, despite the increased utilization of phosphoproteomics in biomedical research, simple and user-friendly tools supporting downstream statistical analysis and interpretation of these highly complex outputs are still lacking. We have therefore developed Phospho-Analyst, which─similar to its sibling LFQ-Analyst─is an easy-to-use, interactive web application specifically designed to reproducibly perform differential expression analyses with "one click" and to visualize phosphoproteomic results in a meaningful and practical manner. Furthermore, if quantitative total proteomic information is available for the same samples, Phospho-Analyst automatically normalizes all phosphoproteomic results to underlying protein abundance levels, thereby ensuring that only genuine changes in phosphorylation events are considered. As such, Phospho-Analyst can not only be used by experienced proteomic veterans but also by researchers without any prior knowledge in (phospho)proteomics, statistics, or bioinformatics. Phospho-Analyst, including a detailed manual, is freely available at https://analyst-suites.org/apps/phospho-analyst/.

Total intravenous anesthesia compared to traditional general anesthesia in shoulder arthroscopy with interscalene block in the beach chair position.

Background: Shoulder arthroscopy is commonly performed in the beach chair position, which has been linked to cerebral oxygen desaturation. Previous studies comparing general anesthesia (GA) to total intravenous anesthesia (TIVA) using propofol indicate that TIVA can preserve cerebral perfusion and autoregulation, as well as shorten recovery time and reduce the incidence of postoperative nausea and vomiting. However, few studies have evaluated the use of TIVA in shoulder arthroscopy. Thus, this study seeks to determine if TIVA is superior to traditional GA methods in terms of improving operating room efficiency, shortening recovery time, and reducing adverse events while theoretically preserving cerebral autoregulation in patients undergoing shoulder arthroscopy in the beach chair position. Methods: This is a retrospective study of patients undergoing shoulder arthroscopy in the beach chair position, comparing 2 anesthetic techniques. One hundred fifty patients were included (75 TIVA and 75 GA). Unpaired t-tests were used to determine statistical significance. Outcome measures included operating room times, recovery times, and adverse events. Results: Compared to GA, TIVA significantly improved phase 1 recovery time (53.2 ± 32.9 min compared to 65.8 ± 41.3 min; P = .037) and total recovery time (120.3 ± 31.0 min compared to 131.5 ± 36.8 min; P = .048). TIVA also decreased time from case finish to out-of-room (6.5 ± 3.5 min compared to 8.4 ± 6.3 min; P = .021). However, the in-room to case start time was slightly longer for the TIVA group (31.8 ± 7.22 min compared to 29.2 ± 4.92 min; P = .012). Although not statistically significant, there were fewer readmissions in the TIVA group compared to the GA group (P = .08), and TIVA had lower rates of postoperative nausea and vomiting (P = .22) and higher intraoperative mean arterial pressures (87.1 ± 11.4 mmHg in the TIVA group compared to 85.0 ± 9.3 mmHg in the GA group; P = .22). Conclusion: TIVA may be a safe and efficient alternative to GA in shoulder arthroscopy in the beach chair position. Larger scale studies are needed to evaluate the risk of adverse events related to impaired cerebral autoregulation in the beach chair position.

Massive and Irreparable Rotator Cuff Tears: A Review of Current Definitions and Concepts.

Background: While massive and irreparable rotator cuff tears (MIRCTs) have been abundantly studied, inconsistent definitions in the literature and theories about pain and dysfunction related to them can be difficult to navigate when considering an individual patient. Purpose: To review the current literature for definitions and critical concepts that drive decision-making for MIRCTs. Study Design: Narrative review. Methods: A search of the PubMed database was performed to conduct a comprehensive literature review on MIRCTs. A total of 97 studies were included. Results: Recent literature reflects added attention to clarifying the definitions of "massive, "irreparable," and "pseudoparalysis." In addition, numerous recent studies have added to the understanding of what generates pain and dysfunction from this condition and have reported on new techniques for addressing them. Conclusion: The current literature provides a nuanced set of definitions and conceptual foundations on MIRCTs. These can be used to better define these complex conditions in patients when comparing current surgical techniques to address MIRCTs, as well as when interpreting the results of new techniques. While the number of effective treatment options has increased, high-quality and comparative evidence on treatments for MIRCTs is lacking.

Merit-based Incentive Payment System Quality Reporting in Urology Practices.

INTRODUCTION: Most urologists are required to participate in Merit-based Incentive Payment System-an alternative payment model in which physicians must track and report quality measures. However, Merit-based Incentive Payment System measures are urology-specific, and it remains unclear what measures urologists are choosing to track and report. METHODS: We performed a cross-sectional analysis of Merit-based Incentive Payment System measures reported by urologists for the most recent performance year. Urologists were categorized by their reporting affiliation (ie, individual, group, or alternative payment model). We identified the measures most frequently reported by urologists. Among reported measures, we identified those that were specific to urological conditions and those that were "topped out" (ie, measures considered indiscriminate by Medicare because high performance is easily achieved). RESULTS: A total of 6,937 urologists reported in Merit-based Incentive Payment System during the 2020 performance year, of whom 14% reported as an individual, 56% as a group, and 30% as an alternative payment model. Among the top 10 most frequently reported measures, none were urology-specific. Eleven percent of urologists reported measures that were directly specific to urological conditions; 65% of individual urologists, 58% of those in groups, and 92% in alternative payment models reported at least 1 or more "topped out" measures. CONCLUSIONS: Most measures reported by urologists are not specific to urological conditions, and therefore performance within Merit-based Incentive Payment System may be a poor indicator of the quality of urological care provided. As Medicare transitions Merit-based Incentive Payment System to implement specific quality measures, the urological community will need to develop and submit measures that will be most impactful for urology patients.

Disease-modifying effects of sodium selenate in a model of drug-resistant, temporal lobe epilepsy.

There are no pharmacological disease-modifying treatments with an enduring effect to mitigate the seizures and comorbidities of established chronic temporal lobe epilepsy (TLE). This study aimed to evaluate for disease modifying effects of sodium selenate treatment in the chronically epileptic rat post-status epilepticus (SE) model of drug-resistant TLE. Wistar rats underwent kainic acid-induced SE or sham. Ten-weeks post-SE, animals received sodium selenate, levetiracetam, or vehicle subcutaneousinfusion continuously for 4 weeks. To evaluate the effects of the treatments, one week of continuous video-EEG was acquired before, during, and 4, 8 weeks post-treatment, followed by behavioral tests. Targeted and untargeted proteomics and metabolomics were performed on post-mortem brain tissue to identify potential pathways associated with modified disease outcomes. Telomere length was investigated as a novel surrogate marker of epilepsy disease severity in our current study. The results showed that sodium selenate treatment was associated with mitigation of measures of disease severity at 8 weeks post-treatment cessation; reducing the number of spontaneous seizures (p< 0.05), cognitive dysfunction (p< 0.05), and sensorimotor deficits (p< 0.01). Moreover, selenate treatment was associated with increased protein phosphatase 2A (PP2A) expression, reduced hyperphosphorylated tau, and reversed telomere length shortening (p< 0.05). Network medicine integration of multi-omics/pre-clinical outcomes identified protein-metabolite modules positively correlated with TLE. Our results provide evidence that treatment with sodium selenate results in a sustained disease-modifying effect in chronically epileptic rats in the post-KA SE model of TLE, including improved comorbid learning and memory deficits.

According to the World Health Organization (WHO), there are around 50 million people with epilepsy worldwide. Although drugs are available to control epileptic seizures, these only provide symptomatic relief. They cannot prevent the condition from worsening, and if people with epilepsy stop taking their medication, there is no lasting effect on the severity or frequency of their seizures. Some epilepsy cases are also resistant to these drugs. This is particularly common in adults with temporal epilepsy, with 30% of people continuing to suffer with seizures despite receiving medication. Current treatments also have no effect on problems with learning, memory and mental health that sometimes accompany drug-resistant epilepsy. Previous studies in animals have identified some potential treatments that could slow the progression of temporal epilepsy, but these have only been shown to work when used at a very early stage. Since most individuals with temporal epilepsy have already started having seizures when they are diagnosed (and it is difficult to predict who will develop the condition), these drugs are unlikely to be useful in practice. Here, Casillas-Espinosa et al. set out to find if a novel drug called sodium selenate can stop the progression of epilepsy and reduce the severity of temporal epilepsy when the condition is fully advanced. To do this, they used an animal model of temporal epilepsy, where rats had been modified to develop spontaneous seizures, resistance to normal anti-seizure medications, and problems with learning and memory. Casillas-Espinosa et al. found that sodium selenate not only reduced the number and severity of seizures in these model rats, but also improved their memory and learning ability. Several rats stopped having seizures altogether even after the treatment had stopped, indicating that sodium selenate had a long-lasting protective effect. Genetic analysis of the rats also revealed that shorter telomeres (special DNA sequences at the ends of chromosomes) correlated with increasing severity of the condition, suggesting that telomere length could help predict who might develop temporal epilepsy or respond best to treatment. This study identifies sodium selenate as a potential treatment that could reverse the progression of temporal epilepsy, even in individuals with advanced symptoms. Later this year, sodium selenate will be trialled in people with drug-resistant temporal epilepsy to determine if the drug benefits humans in the same way. Casillas-Espinosa et al. hope that it will improve participants' epilepsy and, ultimately, their quality of life.

Integrative omics identifies conserved and pathogen-specific responses of sepsis-causing bacteria.

Even in the setting of optimal resuscitation in high-income countries severe sepsis and septic shock have a mortality of 20-40%, with antibiotic resistance dramatically increasing this mortality risk. To develop a reference dataset enabling the identification of common bacterial targets for therapeutic intervention, we applied a standardized genomic, transcriptomic, proteomic and metabolomic technological framework to multiple clinical isolates of four sepsis-causing pathogens: Escherichia coli, Klebsiella pneumoniae species complex, Staphylococcus aureus and Streptococcus pyogenes. Exposure to human serum generated a sepsis molecular signature containing global increases in fatty acid and lipid biosynthesis and metabolism, consistent with cell envelope remodelling and nutrient adaptation for osmoprotection. In addition, acquisition of cholesterol was identified across the bacterial species. This detailed reference dataset has been established as an open resource to support discovery and translational research.

Approaching Artificial Intelligence in Orthopaedics: Predictive Analytics and Machine Learning to Prognosticate Arthroscopic Rotator Cuff Surgical Outcomes.

Machine learning (ML) has not yet been used to identify factors predictive for post-operative functional outcomes following arthroscopic rotator cuff repair (ARCR). We propose a novel algorithm to predict ARCR outcomes using machine learning. This is a retrospective cohort study from a prospectively collected database. Data were collected from the Surgical Outcome System Global Registry (Arthrex, Naples, FL, USA). Pre-operative and 3-month, 6-month, and 12-month post-operative American Shoulder and Elbow Surgeons (ASES) scores were collected and used to develop a ML model. Pre-operative factors including demography, comorbidities, cuff tear, tissue quality, and fixation implants were fed to the ML model. The algorithm then produced an expected post-operative ASES score for each patient. The ML-produced scores were compared to actual scores using standard test-train machine learning principles. Overall, 631 patients who underwent shoulder arthroscopy from January 2011 to March 2020 met inclusion criteria for final analysis. A substantial number of the test dataset predictions using the XGBoost algorithm were within the minimal clinically important difference (MCID) and substantial clinical benefit (SCB) thresholds: 67% of the 12-month post-operative predictions were within MCID, while 84% were within SCB. Pre-operative ASES score, pre-operative pain score, body mass index (BMI), age, and tendon quality were the most important features in predicting patient recovery as identified using Shapley additive explanations (SHAP). In conclusion, the proposed novel machine learning algorithm can use pre-operative factors to predict post-operative ASES scores accurately. This can further supplement pre-operative counselling, planning, and resource allocation. Level of Evidence: III.