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First-generation trabecular metal (TM) backed glenoids reported poor implant survival and were recalled from the market. Second generation TM glenoids have demonstrated promising findings at short- and mid-term follow-up. In our study, we report on clinical and radiographic outcomes of TM glenoids with an average of 10 years of clinical and radiographic follow-up. The charts of 14 TM glenoid patients with minimum 5 years follow-up were retrospectively analyzed. The primary end points included implant survival, range of motion, and patient-reported outcomes. Additionally, radiographic data (metal debris, lateral humeral offset (LHO), acromiohumeral interval (AHI)) were studied. The mean age at surgery was 52 ± 11 years and the mean follow-up time was 10 ± 3 years. Implant survivorship was 100%. Range of motion improved significantly following surgery. Forward elevation changed from 120 ± 22º preoperatively to 155 ± 13º postoperatively (P <.01). The mean external rotation showed a statistically significant increase from 19 ± 30º preoperatively to 54 ± 13º postoperatively (P <.01). Internal rotation improved six vertebral levels on average (P <.01). Pain levels decreased significantly from 7 ± 1 to 2 ± 2 (P <.01) while American Shoulder and Elbow Surgeons Shoulder scores increased from 35 ± 10 to 83 ± 21 (P <.01). Simple Shoulder Test scores demonstrated an improvement from 5 ± 3 to 10 ± 3 (P <.01). No patients had glenoid loosening, metal debris, or radioluency on radiographic imaging. The immediate LHO was 18 (standard deviation [SD] ± 9) and final LHO of 16 (SD ± 8) (P value =.01). The immediate AHI was 12 (SD ± 3) and final AHI was 11 (SD ± 3) (P value =.01). TM backed glenoids should remain in the modern orthopedic surgeon's armamentarium of procedures. This particular glenoid design showed 100% implant survival at a decade following surgery, and provided sustained improvements in range of motion and shoulder function in osteoarthritic patients. [ABSTRACT FROM AUTHOR]

The main objective of this retrospective analysis was to report on the long-term clinical and radiographic outcomes (>10 years) in a series of patients who have previously undergone hemiarthroplasty for proximal humerus fracture. The charts of 11 patients (12 shoulders) who underwent hemiarthroplasty for proximal humerus fractures were retrospectively analyzed and stratified based on tuberosity healed (TH) or tuberosity resorption (TR). The primary end points included range of motion measurements and patient-reported outcome scores. We obtained forward elevation, exterx nal rotation, internal rotation, Simple Shoulder Test, American Shoulder and Elbow Surgeons scores, and Visual Analog Scale (VAS) scores. Tuberosity healing or resorption, acromiohumeral interval, subluxation, and humeral radiolucency were analyzed separately by 2 fellowship-trained orthopedic surgeons. The mean age at surgery for TH patients was 60.0 ± 9.8 years and for TR patients was 57.7 ± 4.3 years. There were 7 cases in tuberosity healing cohort and 5 cases in the tuberosity resorption cohort. Implant survivorship at final follow-up was 100% (7/7) for TH and 60% (3/5) for TR; 2 patients who failed hemiarthroplasty were converted to reverse total shoulder arthroplasty. Mean postoperative forward elevation (TH: 155°, TR: 36°; P value <.01), external rotation (TH: 59°, TR: 28°; P value <.01), and internal rotation (TH:T12, TR:L3; P value =.08) were higher in the TH cohort. American Shoulder and Elbow Surgeons scores (TH: 90, TR: 40; P value <.01) and Simple Shoulder Test scores (TH: 9, TR: 2; P value <.01) were statistically significant between the 2 cohorts while VAS scores approached significance (mean VAS [TH: 1, TR: 4; P value =.08]). To our knowledge, this study provides the longest follow-up to date for outcomes following hemiarthroplasty with fracture. Significant improvements in shoulder function and reduction in pain levels are sustainable even after 19 years in patients whose tuberosity heals. Hemiarthroplasty remains a viable option for younger candidates whose tuberosity will heal postoperatively. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) can lead to debilitating pain, decreased bone stock, and poor rotator cuff quality in afflicted patients. Patients with chronic pain from RA may necessitate surgical intervention, including shoulder arthroplasty, at a younger age than their osteoarthritic counterparts. For several decades, anatomic total shoulder arthroplasty (TSA) or hemiarthroplasty remained the dominant treatments for RA patients. The objective of this abstract is to report on mid-term to long-term outcomes following TSA for RA. This study retrospectively analyzed patients who necessitated TSA for RA. Range of motion scores (forward elevation, external rotation, and internal rotation) and patient-reported outcomes (American Shoulder and Elbow Surgeons, Simple Shoulder Test, and Visual Analog Scale scores) were compared preoperatively and postoperatively. Preoperative and postoperative radiographic measures (lateral humeral offset, acromiohumeral interval, and subluxation) were reviewed by 2 fellowship-trained orthopedic surgeons and the averages were used for analysis. Included in the analysis were 13 patients (17 shoulders) with an average follow-up time of 8.1 ± 3.6 years. The mean age was 65.3 ± 10.5 years. Forward flexion (Preop: 112o ± 43o, Postop: 145o ± 35o; P =.03), external rotation (Preop: 31o ± 20o, Postop: 46o ± 15o; P =.04), and internal rotation (Preop: L2, Postop: T11; P =.02) all improved significantly when preoperative and postoperative values were compared. Furthermore, American Shoulder and Elbow Surgeons (Preop: 33 ± 20, Postop: 74 ± 19; P =.0002), Simple Shoulder Test (Preop: 4 ± 2, Postop: 8 ± 4; P =.003), and Visual Analog Scale pain (Preop: 7 ± 3, Postop: 2 ± 2; P =.002) scores all significantly improved. Analysis of preoperative and postoperative radiographs showed a significant difference in lateral humeral offset (Preop: 14 ± 3, Final: 8 ± 9; P =.02) and acromiohumeral interval (Preop: 11 ± 3, Postop: 7 ± 3; P =.01) measurements; glenoid radiolucency was seen in 10/17 patients at follow-up. This study contributes to the available literature on TSA for RA at mid-term to long-term follow-up. We show that improvements are obtainable at mid-term evaluation, showing significant pain reduction and increased shoulder function and range of motion. Ultimately, this study demonstrates that TSA is an option for RA patients who require shoulder replacement. [ABSTRACT FROM AUTHOR]

As of 2018, upwards of 42% of the US adult population was considered obese based on body mass index (BMI) scales. With the annual number of total joint replacements increasing, this study aimed to evaluate the impact BMI has on anatomic total shoulder arthroplasty (aTSA) outcomes. This was a retrospective analysis of 128 shoulders requiring primary aTSA. Patients were stratified into 3 cohorts based on their BMI at surgery: underweight/normal weight (U/NW; BMI ≤25.0), overweight (25.0 < BMI ≤ 30.0), and obese (BMI >30.0). BMI was separately analyzed as a continuous variable. Clinical endpoints were range of motion scores, including forward elevation, external rotation, and internal rotation, and patient-reported outcomes, including visual analog scale (VAS) scores, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) scores, and the Simple Shoulder Test (SST). Survivorship curves were calculated using Kaplan-Meier analysis. Forty-four, 50, and 34 patient shoulders were in the U/NW, overweight, and obese cohorts, respectively. The mean follow-up time was 11.4 years. The U/NW cohort had more females (73%) compared with the overweight (34%; P =.0030) and obese (35%; P =.0015) groups; no differences were seen in revision rates. BMI was negatively correlated with age at surgery (r = −0.19, P =.014); it was not correlated with any of the 6 postoperative clinical endpoints. All 3 cohorts saw significant improvements in forward elevation, external rotation, internal rotation and VAS, ASES, and SST scores when compared preoperatively to postoperatively (P <.001). There were no significant differences between the 3 cohorts with respect to postoperative range of motion. Postoperative ASES scores were higher for the overweight cohort (82.6 ± 18.6) compared with both the U/NW (63.0 ± 25.1) and obese cohorts (70.5 ± 26.8) (P <.001). The overweight cohort also had higher SST (P =.0012) postoperative scores compared with the U/NW and obese cohorts; VAS scores were comparable between groups (P =.12). The nonobese (BMI <30) group (n = 94) showed 5-, 10-, and 15-year implant survival of 98.9%, 94.9%, and 83.9%, respectively compared to 97.1%, 93.7%, and 87.0% in the obese (BMI ≥30) group (n = 34). The log rank test revealed no significant difference in survival curves (P =.82). To our knowledge, this is the longest follow-up study analyzing clinical endpoints stratified by BMI for aTSA. We saw that patients with a higher BMI required shoulder replacement at a significantly younger age. However, we also report that regardless of BMI, all patients saw significant improvements in patient-reported outcomes and range of motion scores postoperatively. [ABSTRACT FROM AUTHOR]

Implementing novel tools that identify contributors to the cost of orthopedic procedures can help hospitals maximize efficiency, minimize waste, improve surgical decision-making, and practice value-based care. The purpose of this study was to develop and internally validate a machine learning algorithm to identify key drivers of total charges after ambulatory arthroscopic rotator cuff repair and compare its performance with a state-of-the-art statistical learning model. A retrospective review of the New York State Ambulatory Surgery and Services Database was performed to identify patients who underwent elective outpatient rotator cuff repair (RCR) from 2015 to 2016. Initial models were constructed using patient characteristics (age, gender, insurance status, patient income, Elixhauser Comorbidity Index) as well as intraoperative variables (concomitant procedures and services, operative time). These were subsequently entered into 5 separate machine learning algorithms and a generalized additive model using natural splines. Global variable importance and partial dependence curves were constructed to identify the greatest contributors to cost. A total of 33,976 patients undergoing ambulatory RCR were included. Median total charges after ambulatory RCR were $16,017 (interquartile range: $11,009-$22,510). The ensemble model outperformed the generalized additive model and demonstrated the best performance on internal validation (root mean squared error: $7112, 95% confidence interval: 7036-7188; logarithmic root mean squared error: 0.354, 95% confidence interval: 0.336-0.373, R2: 0.53), and identified major drivers of total charges after RCR as increasing operating room time, patient income level, number of anchors used, use of local infiltration anesthesia/peripheral nerve blocks, non-White race/ethnicity, and concurrent distal clavicle excision. The model was integrated into a web-based open-access application capable of providing individual predictions and explanations on a case-by-case basis. This study developed an ensemble supervised machine learning algorithm that outperformed a sophisticated statistical learning model in predicting total charges after ambulatory RCR. Important contributors to total charges included operating room time, duration of care, number of anchors used, type of anesthesia, concomitant distal clavicle excision, community characteristics, and patient demographic factors. Generation of a patient-specific payment schedule based on the Agency for Healthcare Research and Quality risk of mortality highlighted the financial risk assumed by physicians in flat episodic reimbursement schedules given variable patient comorbidities and the importance of an accurate prediction algorithm to appropriately reward high-value care at low costs. [ABSTRACT FROM AUTHOR]

The objective of this study is to understand the clinical and radiographic outcomes for uncemented humeral stems in reverse total shoulder arthroplasty. The usage of an uncemented stem is increasing in incidence, and it is important to understand both outcomes and complications for this stem. Studies were included if range of motion, radiographic outcomes, and complication outcomes in relation to uncemented humeral stems in reverse total shoulder arthroplasty were mentioned. Studies were excluded if they did not provide clinical data about uncemented stems, such as surgical technique manuscripts, case reports, and animal studies. PubMed, MEDLINE (Ovid, New York, NY, USA), Scopus (www.scopus.com), and Web of Science were queried using relevant search terms in January 2021. Paired t -tests were done to present and synthesize the results. Twenty-six studies were included in this review. Four were of Level III evidence, and 22 were of Level IV evidence, totaling 1620 shoulders. Forward flexion improved from 67° ± 18° to 126° ± 15° (P <.001) and external rotation improved from 18° ± 8° to 36° ± 12° (P =.002). Constant scores increased from 28 ± 10 to 68 ± 14 (P <.001) and visual analog scale scores decreased from 7 ± 2 to 2 ± 2 (P <.001). Radiographic outcomes included scapular notching (n = 173), tuberosity union (n = 120), and radiolucent lines (n = 329). The most frequently observed complications in this systematic review included fracture (n = 52), infection (n = 24), and shoulder dislocation (n = 16). Uncemented humeral stems show significant improvements in range of motion and patient-reported outcomes. Perioperative fractures and scapular notching continue to be prevalent in this population. Analysis of previous literature indicates that humeral loosening is comparative between cemented and uncemented humeral stems, but operative time is significantly reduced in uncemented stems. Limitations of this review include the paucity of Level III or higher literature, which makes it challenging to compare uncemented and cemented humeral stem outcomes. Level IV, Systematic Review [ABSTRACT FROM AUTHOR]

[Display omitted] The norcembranoid and cembranoid diterpenoids represent an intriguing class of natural products isolated from marine sources. Their chemical synthesis has been a challenging and exciting field of research over the past two decades, owing largely to their structural complexity. We recently disclosed a total synthesis of a member of this class, ineleganolide, in a 23 step longest linear sequence. In search of a shorter, more efficient route, we have devised a new strategy for the synthesis of a key bicyclic enone. Disclosed herein is our improved synthesis of this strained intermediate, completing the formal synthesis of ineleganolide in only 14 steps, thereby shortening our previous synthesis by 9 steps. Dedicated to Prof. Thomas Maimone on his receipt of the Tetrahedron Young Investigator Award 2024. [ABSTRACT FROM AUTHOR]

Purpose: To compare the efficacy of a subacromial injection (SAI) with a single-shot interscalene block (ISB) for immediate postoperative pain relief after outpatient arthroscopic rotator cuff repair (ARCR).Methods: We performed a retrospective chart review of consecutive patients who underwent ARCR. Patients received either an ISB before the procedure or an SAI after the procedure. Preoperative baseline patient characteristics were collected and compared. Visual analog scale (VAS) pain scores were recorded preoperatively, at 15-minute intervals over a 120-minute period in the postanesthesia care unit (PACU), and at discharge. Differences in VAS scores between groups were compared with known values of the minimal clinically important difference, and the percentage of patients with VAS scores below the patient acceptable symptom state was tabulated. Differences between preoperative characteristics were assessed using the Mann-Whitney U, Fisher exact, or χ2 test. The Mann-Whitney U test was also used to evaluate VAS scores and total time spent in the PACU between groups.Results: The median VAS score was significantly lower in the ISB group at PACU admission, at all intervals throughout the PACU stay, and at discharge (P < .0001). The median total time in the PACU was 107 minutes (25th percentile-75th percentile, 90-120 minutes) and 210 minutes (25th percentile-75th percentile, 175-274 minutes) in the ISB and SAI groups, respectively (P < .0001). Between-group differences in VAS scores were greater than the values of the minimal clinically important difference at each measured interval. A total of 98% and 67% of patients in the ISB and SAI groups, respectively, were discharged with VAS scores below the patient acceptable symptom state of 3.Conclusions: Patients receiving an ISB experience significantly less pain than those receiving an SAI. In addition, they are discharged home from the PACU in half the time as patients receiving an SAI. On the basis of the comparative efficacy, an SAI cannot replace an ISB after ARCR. The ISB should therefore remain the standard of care as an adjunct to postoperative analgesia for patients who undergo outpatient ARCR.Level Of Evidence: Level III, retrospective, comparative therapeutic trial. [ABSTRACT FROM AUTHOR]

A key feature of age-related hearing loss is a reduction in the expression of inhibitory neurotransmitters in the central auditory system. This loss is partially responsible for changes in central auditory processing, as inhibitory receptive fields play a critical role in shaping neural responses to sound stimuli. Vigabatrin (VGB), an antiepileptic agent that irreversibly inhibits γ-amino butyric acid (GABA) transaminase, leads to increased availability of GABA throughout the brain. This study used multi-channel electrophysiology measurements to assess the excitatory frequency response areas in old CBA mice to which VGB had been administered. We found a significant post-VGB reduction in the proportion of V-type shapes, and an increase in primary-like excitatory frequency response areas. There was also a significant increase in the mean maximum driven spike rates across the tonotopic frequency range of all treated animals, consistent with observations that GABA buildup within the central auditory system increases spike counts of neural receptive fields. This increased spiking is also seen in the rate-level functions and seems to explain the improved low-frequency thresholds. [ABSTRACT FROM AUTHOR]

Interpretation of high-resolution CT images plays an important role in the diagnosis and management of interstitial lung diseases. However, interreader variation may exist due to varying levels of training and expertise. This study aims to evaluate interreader variation and the role of thoracic radiology training in classifying interstitial lung disease (ILD). This is a retrospective study where seven physicians (radiologists, thoracic radiologists, and a pulmonologist) classified the subtypes of ILD of 128 patients from a tertiary referral center, all selected from the Interstitial Lung Disease Registry which consists of patients from November 2014 to January 2021. Each patient was diagnosed with a subtype of interstitial lung disease by a consensus diagnosis from pathology, radiology, and pulmonology. Each reader was provided with only clinical history, only CT images, or both. Reader sensitivity and specificity and interreader agreements using Cohen's κ were calculated. Interreader agreement based only on clinical history, only on radiologic information, or combination of both was most consistent amongst readers with thoracic radiology training, ranging from fair (Cohen's κ: 0.2–0.46), moderate to almost perfect (Cohen's κ: 0.55–0.92), and moderate to almost perfect (Cohen's κ: 0.53–0.91) respectively. Radiologists with any thoracic training showed both increased sensitivity and specificity for NSIP as compared to other radiologists and the pulmonologist when using only clinical history, only CT information, or combination of both (p < 0.05). Readers with thoracic radiology training showed the least interreader variation and were more sensitive and specific at classifying certain subtypes of ILD. Thoracic radiology training may improve sensitivity and specificity in classifying ILD based on HRCT images and clinical history. • Compared to other readers, thoracic radiologists displayed better overall sensitivity and specificity when diagnosing ILD • Nonspecific interstitial pneumonia was most accurately diagnosed by thoracic radiologists • Readers with thoracic radiology training showed the most interreader agreement when classifying ILD based on HRCT and clinical history [ABSTRACT FROM AUTHOR]

Full-grown Xenopus oocytes are arrested at the prophase of the first meiotic division in a G2-like state. Progesterone triggers meiotic resumption also called the G2/M transition. This event is characterized by germinal vesicle breakdown (GVBD) and by a burst in phosphorylation level that reflects activation of M-phase-promoting factor (MPF) and MAPK pathways. Besides phosphorylation and ubiquitin pathways, increasing evidence has suggested that the cytosolic and nucleus-specific O-GIcNAc glycosylation also contributes to cell cycle regulation. To investigate the relationship between O-GlcNAc and cell cycle, Xenopus oocyte, in which most of the M-phase regulators have been discovered, was used. Alloxan, an O-GlcNAc transferase inhibitor, blocked G2/M transition in a concentration-dependent manner. Alloxan prevented GVBD and both MPF and MAPK activations, either triggered by progesterone or by egg cytoplasm injection. The addition of detoxifying enzymes (SOD and catalase) did not rescue GVBD, indicating that the alloxan effect did not occur through reactive oxygen species production. These results were strengthened by the use of a benzoxazolinone derivative (XI), a new O-GlcNAc transferase inhibitor. Conversely, injection of O-(2-acetamido-2-deoxy-D-glucopyrano-sylidene)amino-N-phenylcarbamate, an O-GlcNAcase inhibitor, accelerated the maturation process. Glutamine:fructose-6-phosphate amidotransferase inhibitors, azaserine and 6-diazo-5-oxonorleucine, failed to prevent GVBD. Such a strategy appeared to be inefficient; indeed, UDP-GlcNAc assays in mature and in mature oocytes revealed a constant pool of the nucleotide sugar. Finally, we observed that cydin B2, the MPF regulatory subunit, was associated with an unknown O-GlcNAc partner. The present work underlines a crucial role for O-GlcNAc in G2/M transition and strongly suggests that its function is required for cell cycle regulation. [ABSTRACT FROM AUTHOR]