Systemic versus localized Bacillus Calmette Guérin immunotherapy of bladder cancer promotes an anti-tumoral microenvironment: Novel role of trained immunity.

Treatment for higher-risk non-muscle invasive bladder cancer (NMIBC) involves intravesical immunotherapy with Bacillus Calmette Guérin (BCG); however, disease recurrence and progression occur frequently. Systemic immunity is critical for successful cancer immunotherapy; thus, recurrence of NMIBC may be due to suboptimal systemic activation of anti-tumor immunity after local immunotherapy. We previously reported that systemically acquired trained immunity (a form of innate immune memory) in circulating monocytes is associated with increased time-to-recurrence in patients with NMIBC treated with BCG. Herein, we used a mouse model of NMIBC to compare the effects of intravesical versus intravenous (systemic) BCG immunotherapy on the local and peripheral immune microenvironments. We also assessed whether BCG-induced trained immunity modulates anti-tumor immune responses. Compared with intravesical BCG, which led to a tumor-promoting immune microenvironment, intravenous BCG resulted in an anti-tumoral bladder microenvironment characterized by increased proportions of cytotoxic T lymphocytes (CTLs), and decreased proportions of myeloid-derived suppressor cells. Polarization toward anti-tumoral immunity occurred in draining lymph nodes, spleen, and bone marrow following intravenous versus intravesical BCG treatment. Pre-treatment with intravesical BCG was associated with increased rate of tumor growth compared with intravenous BCG pre-treatment. Trained immunity contributed to remodeling of the tumor immune microenvironment, as co-instillation of BCG-trained macrophages with ovalbumin-expressing bladder tumor cells increased the proportion of tumor-specific CTLs. Furthermore, BCG-trained dendritic cells exhibited enhanced antigen uptake and presentation and promoted CTL proliferation. Our data support the concept that systemic immune activation promotes anti-tumor responses, and that BCG-induced trained immunity is important in driving anti-tumor adaptive immunity.

Click-chemistry mediated synthesis of OTBN-1,2,3-Triazole derivatives exhibiting STK33 inhibition with diverse anti-cancer activities.

There is a continuous and pressing need to establish new brain-penetrant bioactive compounds with anti-cancer properties. To this end, a new series of 4'-((4-substituted-4,5-dihydro-1H-1,2,3-triazol-1-yl)methyl)-[1,1'-biphenyl]-2-carbonitrile (OTBN-1,2,3-triazole) derivatives were synthesized by click chemistry. The series of bioactive compounds were designed and synthesized from diverse alkynes and N3-OTBN, using copper (II) acetate monohydrate in aqueous dimethylformamide at room temperature. Besides being highly cost-effective and significantly reducing synthesis, the reaction yielded 91-98 % of the target products without the need of any additional steps or chromatographic techniques. Two analogues exhibit promising anti-cancer biological activities. Analogue 4l shows highly specific cytostatic activity against lung cancer cells, while analogue 4k exhibits pan-cancer anti-growth activity. A kinase screen suggests compound 4k has single-digit micromolar activity against kinase STK33. High STK33 RNA expression correlates strongly with poorer patient outcomes in both adult and pediatric glioma. Compound 4k potently inhibits cell proliferation, invasion, and 3D neurosphere formation in primary patient-derived glioma cell lines. The observed anti-cancer activity is enhanced in combination with specific clinically relevant small molecule inhibitors. Herein we establish a novel biochemical kinase inhibitory function for click-chemistry-derived OTBN-1,2,3-triazole analogues and further report their anti-cancer activity in vitro for the first time.

Novel tetrahydropyran-triazole hybrids with antiproliferative activity against human tumor cells.

A series of new hybrid compounds was prepared combining tetrahydropyran rings with different aromatic systems by means of a 1,2,3-triazole, using a building block strategy. The design of these structures was guided by Lead-Likeness and Molecular Analysis (LLAMA) software, adding modifications to our most potent scaffold (the tetrahydropyran ring) to generate promising "lead-like" candidates, which were subsequently compared against reported anticancer compounds. Our synthesized compounds demonstrated significant antiproliferative activity when compared with the standards cisplatin and 5-fluorouracil, across a panel of six different tumor cell lines. Moreover, compared with our group's previous hybrid compounds, these new structures exhibit similar activity while offering simpler synthesis and greater potential for structural diversification, a fact that was previously an issue. Further investigations on the most active compounds included assessments of reproductive cell survival, inhibition of cell migration, and effects on nuclear morphology, indicating potential diverse mechanisms of action for these compounds. Pharmacokinetic properties were also calculated for the whole series of compounds using the pkCSM online software.

Elevated HbA1c is not associated with reoperation following arthroscopic rotator cuff repair in patients with diabetes mellitus.

BACKGROUND: Hyperglycemia is a known risk factor for tendon degeneration due to oxidative stresses from production of advanced glycosylation end products. In patients with diabetes mellitus (DM), analysis of glycated hemoglobin (HbA1c) provides a 3-month window into a patient's glucose control. No guidelines exist for ideal preoperative HbA1c and glucose control prior to arthroscopic rotator cuff repair. This study evaluated if a critical HbA1c level is associated with reoperation following arthroscopic rotator cuff repair. METHODS: We retrospectively evaluated patients with DM who underwent primary arthroscopic rotator cuff repair from January 2014 to December 2018 at a single institution. Patients required a preoperative HbA1c within 3 months of surgery. Medical records were queried to evaluate for reoperation and identify the subsequent procedures performed. Univariate statistical analysis was performed to assess factors associated with reoperation (P < .05 considered significant). Threshold, area under the curve (AUC), analysis was performed to assess if a critical HbA1c value was associated with reoperation. RESULTS: A total of 402 patients met inclusion criteria. Patients had an average age of 65.5 years (range 40-89) at time of surgery; 244 (60.6%) patients were male; and average body mass index was 32.96 ± 5.81. Mean HbA1c was 7.36 (range 5.2-12). Thirty-three patients (8.2%) underwent subsequent reoperation. Six patients (1.5%) underwent capsular release and lysis of adhesions, 20 patients (5.0%) underwent a revision rotator cuff surgery, combination revision rotator cuff repair and lysis of adhesions, graft-augmented revision repair, or superior capsular reconstruction, and 7 patients (1.7%) underwent revision to reverse shoulder arthroplasty (1.7%). There were no cases of reoperation for infection. On AUC analysis, no critical HbA1c value was identified to predispose to reoperation. Interestingly, elevated preoperative American Society of Anesthesiologists (ASA) physical status classification score (2.8 vs. 2.28, P = .001) was associated with a higher reoperation rate. DISCUSSION: In patients with DM, preoperative HbA1c is not a predictive factor for surgical failure requiring reoperation. Stable glycemic control is important to a patient's overall health and may play a role in minimizing postoperative medical complications, but an elevated preoperative HbA1c should not be a strict surgical contraindication for arthroscopic rotator cuff repair. In patients with DM, an elevated ASA score is associated with an increased rate of subsequent reoperation; diabetic patients should be counseled accordingly.

Reverse Versus Anatomic Total Shoulder Arthroplasty for Glenohumeral Osteoarthritis with Intact Cuff: A Meta-Analysis of Clinical Outcomes.

BACKGROUND: Anatomic and reverse shoulder arthroplasty (TSA, RSA) have surged in popularity in recent years. While RSA is Food and Drug Administration (FDA) approved for cases of rotator cuff tear arthropathy, indications have expanded to include, among others, primary glenohumeral osteoarthritis (GHOA). METHODS: PubMed, Cochrane, and Google Scholar (pages 1-20) were queried through November 2023. Inclusion criteria consisted of studies that compared the utility of TSA to that of RSA for the treatment of GHOA with intact rotator cuff with respect to adverse events, patient-reported outcomes, and range of motion. The ROBINS-I tool was used to assess the risk of bias in the included non-randomized studies, and Review Manager 5.4 was used for statistical analysis. P-values <0.05 were deemed significant. RESULTS: Fourteen studies met the above inclusion criteria. Twelve studies reported adverse outcomes, with the RSA group having a lower rate of complications (odds-ratio=0.54, p=0.004) and reoperations (odds-ratio=0.31, p<.001) relative to TSA at an average follow-up of 3.4 years. Four studies reported SPADI and UCLA scores, while five reported SST scores. These studies showed superior SPADI (p=0.040), UCLA(p=0.006), and SST(p=0.040) scores among the RSA group. No significant differences were seen with regards to other patient reported outcomes. Ten studies reported on range of motion, and the RSA group had a significantly lower external rotation relative to the TSA group (p<.001) while other range of motion parameters did not show statistically significant differences. CONCLUSION: The present study provides support for RSA as a reasonable surgical option for patients with GHOA and an intact rotator cuff, with lower rates of adverse events and better outcomes relative to TSA, although at the expense of decreased external rotation. Patient education and counseling is key in order to decide optimal treatment as part of a shared decision-making process, as well as setting appropriate expectations.

Effect of vitamin E-enhanced highly cross-linked polyethylene on wear rate and particle debris in anatomic total shoulder arthroplasty: a biomechanical comparison to ultrahigh-molecular-weight polyethylene.

BACKGROUND: Particle-induced osteolysis resulting from polyethylene wear remains a source of implant failure in anatomic total shoulder designs. Modern polyethylene components are irradiated in an oxygen-free environment to induce cross-linking, but reducing the resulting free radicals with melting or heat annealing can compromise the component's mechanical properties. Vitamin E has been introduced as an adjuvant to thermal treatments. Anatomic shoulder arthroplasty models with a ceramic head component have demonstrated that vitamin E-enhanced polyethylene show improved wear compared with highly cross-linked polyethylene (HXLPE). This study aimed to assess the biomechanical wear properties and particle size characteristics of a novel vitamin E-enhanced highly cross-linked polyethylene (VEXPE) glenoid compared to a conventional ultrahigh-molecular-weight polyethylene (UHMWPE) glenoid against a cobalt chromium molybdenum (CoCrMo) head component. METHODS: Biomechanical wear testing was performed to compare the VEXPE glenoid to UHMWPE glenoid with regard to pristine polyethylene wear and abrasive endurance against a polished CoCrMo alloy humeral head in an anatomic shoulder wear-simulation model. Cumulative mass loss (milligrams) was recorded, and wear rate calculated (milligrams per megacycle [Mc]). Under pristine wear conditions, particle analysis was performed, and functional biologic activity (FBA) was calculated to estimate particle debris osteolytic potential. In addition, 95% confidence intervals for all testing conditions were calculated. RESULTS: The average pristine wear rate was statistically significantly lower for the VEXPE glenoid compared with the HXLPE glenoid (0.81 ± 0.64 mg/Mc vs. 7.00 ± 0.45 mg/Mc) (P < .05). Under abrasive wear conditions, the VEXPE glenoid had a statistically significant lower average wear rate compared with the UHMWPE glenoid comparator device (18.93 ± 5.80 mg/Mc vs. 40.47 ± 2.63 mg/Mc) (P < .05). The VEXPE glenoid demonstrated a statistically significant improvement in FBA compared with the HXLPE glenoid (0.21 ± 0.21 vs. 1.54 ± 0.49 (P < .05). CONCLUSIONS: A new anatomic glenoid component with VEXPE demonstrated significantly improved pristine and abrasive wear properties with lower osteolytic particle debris potential compared with a conventional UHMWPE glenoid component. Vitamin E-enhanced polyethylene shows early promise in shoulder arthroplasty components. Long-term clinical and radiographic investigation needs to be performed to verify if these biomechanical wear properties translate to diminished long-term wear, osteolysis, and loosening.

Trends and outcomes of outpatient total shoulder arthroplasty after its removal from CMS's inpatient-only list.

BACKGROUND: In January 2021, the US Medicare program approved reimbursement of outpatient total shoulder arthroplasties (TSA), including anatomic and reverse TSAs. It remains unclear whether shifting TSAs from the inpatient to outpatient setting has affected clinical outcomes. Herein, we describe the rate of outpatient TSA growth and compare inpatient and outpatient TSA complications, readmissions, and mortality. METHODS: Medicare fee-for-service claims for 2019-2022Q1 were analyzed to identify the trends in outpatient TSAs and to compare 90-day postoperative complications, all-cause hospital readmissions, and mortality between outpatients and inpatients. Outpatient cases were defined as those discharged on the same day of the surgery. To reduce the COVID-19 pandemic's impact and selection bias, we excluded 2020Q2-Q4 data and used propensity scores to match 2021-2022Q1 outpatients with inpatients from the same period (the primary analysis) and from 2019-2020Q1 (the secondary analysis), respectively. We performed both propensity score-matched and -weighted multivariate analyses to compare outcomes between the two groups. Covariates included sociodemographics, preoperative diagnosis, comorbid conditions, the Hierarchical Condition Category risk score, prior year hospital/skilled nursing home admissions, annual surgeon volume, and hospital characteristics. RESULTS: Nationally, the proportion of outpatient TSAs increased from 3% (619) in 2019Q1 to 22% (3456) in 2021Q1 and 38% (6778) in 2022Q1. A total of 55,166 cases were identified for the primary analysis (14,540 outpatients and 40,576 inpatients). Overall, glenohumeral osteoarthritis was the most common indication for surgery (70.8%), followed by rotator cuff pathology (14.6%). The unadjusted rates of complications (1.3 vs 2.4%, P < .001), readmissions (3.7 vs 6.1%, P < .001), and mortality (0.2 vs 0.4%, P = .024) were significantly lower among outpatient TSAs than inpatient TSAs. Using 1:1 nearest matching, 12,703 patient pairs were identified. Propensity score-matched multivariate analyses showed similar rates of postoperative complications, hospital readmissions, and mortality between outpatients and inpatients. Propensity score-weighted multivariate analyses resulted in similar conclusions. The secondary analysis showed a lower hospital readmission rate in outpatients (odds ratio: 0.8, P < .001). CONCLUSIONS: There has been accelerated growth in outpatient TSAs since 2019. Outpatient and inpatient TSAs have similar rates of postoperative complication, hospital readmission, and mortality.

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.

Racial and Gender Disparities in Utilization of Outpatient Total Shoulder Arthroplasties.

BACKGROUND: Utilization in outpatient total shoulder arthroplasties (TSAs) has increased significantly in recent years. It remains largely unknown whether utilization of outpatient TSA differs across gender and racial groups. This study aimed to quantify racial and gender disparities both nationally and by geographic regions. METHODS: 168,504 TSAs were identified using Medicare fee-for-service (FFS) inpatient and outpatient claims data and beneficiary enrollment data from 2020 to 2022Q4. The percentage of outpatient cases, defined as cases discharged on the same day of surgery, was evaluated by racial and gender groups and by different census divisions. A multivariate logistics regression model controlling for patient socio-demographic information (white vs. non-white race, age, gender, and dual eligibility for both Medicare and Medicaid), hierarchical condition category (HCC) score, hospital characteristics, year fixed effects, and patient residency state fixed effects was performed. RESULTS: The TSA volume per 1000 beneficiaries was 2.3 for the White population compared to 0.8, 0.6 and 0.3 for the Black, Hispanic, and Asian population, respectively. A higher percentage of outpatient TSAs were in White patients (25.6%) compared to Black patients (20.4%) (p < 0.001). The Black TSA patients were also younger, more likely to be female, more likely to be dually eligible for Medicaid, and had higher HCC risk scores. After controlling for patient socio-demographic characteristics and hospital characteristics, the odds of receiving outpatient TSAs were 30% less for Black than the White group (OR 0.70). Variations were observed across different census divisions with South Atlantic (0.67, p < 0.01), East North Central (0.56, p < 0.001), and Middle Atlantic (0.36, p < 0.01) being the four regions observed with significant racial disparities. Statistically significant gender disparities were also found nationally and across regions, with an overall odds ratio of 0.75 (p < 0.001). DISCUSSION: Statistically significant racial and gender disparities were found nationally in outpatient TSAs, with Black patients having 30% (p < 0.001) fewer odds of receiving outpatient TSAs than white patients, and female patients with 25% (p < 0.001) fewer odds than male patients. Racial and gender disparities continue to be an issue for shoulder arthroplasties after the adoption of outpatient TSAs.

Comparison of nucleocapsid and spike antibody ELISAs for determining SARS-CoV-2 seropositivity in Kenyan women and infants.

A multitude of enzyme-linked immunosorbent assays (ELISAs) has been developed to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies since the coronavirus disease 2019 pandemic started in late 2019. Assessing the reliability of these assays in diverse global populations is critical. This study compares the use of the commercially available Platelia Total Ab Assay (Bio-Rad) nucleocapsid ELISA to the widely used Mount Sinai spike IgG ELISA in a Kenyan population seroprevalence study. Using longitudinal plasma specimens collected from a mother-infant cohort living in Nairobi, Kenya between May 2019 and December 2020, this study demonstrates that the two assays have a high qualitative agreement (92.7%) and strong correlation of antibody levels (R2 = 0.973) in repeated measures. Within this cohort, seroprevalence detected by either ELISA closely resembled previously published seroprevalence estimates for Kenya during the sampling period and no significant difference in the incidence of SARS-CoV-2 antibody detection by either assay was observed. Assay comparability was not affected by HIV exposure status. These data support the use of the Platelia SARS-CoV-2 Total Ab ELISA as a suitable high-throughput method for seroprevalence studies in Kenya.

Next-generation Sequencing Results Require Higher Inoculum for Cutibacterium acnes Detection Than Conventional Anaerobic Culture.

BACKGROUND: Cutibacterium acnes has been described as the most common causative microorganism in prosthetic shoulder infections. Conventional anaerobic culture or molecular-based technologies are usually used for this purpose, but little to no concordance between these methodologies (k = 0.333 or less) has been observed. QUESTIONS/PURPOSES: (1) Is the minimum C. acnes load for detection higher for next-generation sequencing (NGS) than for anaerobic conventional culture? (2) What duration of incubation is necessary for anaerobic culture to detect all C. acnes loads? METHODS: Five C. acnes strains were tested for this study: Four strains were causing infection and were isolated from surgical samples. Meanwhile, the other was a reference strain commonly used as a positive and quality control in microbiology and bioinformatics. To create inoculums with varying degrees of bacterial load, we began with a standard bacterial suspension at 1.5 x 10 8 colony-forming units (CFU)/mL and created six more diluted suspensions (from 1.5 x 10 6 CFU/mL to 1.5 x 10 1 CFU/mL). Briefly, to do so, we transferred 200 µL from the tube with the highest inoculum (for example, 1.5 x 10 6 CFU/mL) to the following dilution tube (1.5 x 10 5 CFU/mL; 1800 µL of diluent + 200 µL of 1.5 x 10 6 CFU/mL). We serially continued the transfers to create all diluted suspensions. Six tubes were prepared per strain. Thirty bacterial suspensions were tested per assay. Then, 100 µL of each diluted suspension was inoculated into brain heart infusion agar with horse blood and taurocholate agar plates. Two plates were used per bacterial suspension in each assay. All plates were incubated at 37°C in an anaerobic chamber and assessed for growth after 3 days of incubation and daily thereafter until positive or Day 14. The remaining volume of each bacterial suspension was sent for NGS analysis to identify bacterial DNA copies. We performed the experimental assays in duplicate. We calculated mean DNA copies and CFUs for each strain, bacterial load, and incubation timepoint assessed. We reported detection by NGS and culture as a qualitative variable based on the identification or absence of DNA copies and CFUs, respectively. In this way, we identified the minimum bacterial load detected by NGS and culture, regardless of incubation time. We performed a qualitative comparison of detection rates between methodologies. Simultaneously, we tracked C. acnes growth on agar plates and determined the minimum incubation time in days required for CFU detection in all strains and loads examined in this study. Growth detection and bacterial CFU counting were performed by three laboratory personnel, with a high intraobserver and interobserver agreement (κ > 0.80). A two-tailed p value below 0.05 was considered statistically significant. RESULTS: Conventional cultures can detect C. acnes at a load of 1.5 x 10 1 CFU/mL, whereas NGS can detect bacteria when the concentration was higher, at 1.5 x 10 2 CFU/mL. This is represented by a lower positive detection proportion (73% [22 of 30]) for NGS than for cultures (100% [30 of 30]); p = 0.004). By 7 days, anaerobic cultures were able to detect all C. acnes loads, even at the lowest concentrations. CONCLUSION: When NGS is negative and culture is positive for C. acnes , there is likely a low bacterial load. Holding cultures beyond 7 days is likely unnecessary. CLINICAL RELEVANCE: This is important for treating physicians to decide whether low bacterial loads necessitate aggressive antibiotic treatment or whether they are more likely contaminants. Cultures that are positive beyond 7 days likely represent contamination or bacterial loads even below the dilution used in this study. Physicians may benefit from studies designed to clarify the clinical importance of the low bacteria loads used in this study at which both methodologies' detection differed. Moreover, researchers might explore whether even lower C. acnes loads have a role in true periprosthetic joint infection.

Higher Surgeon Volume is Associated With a Lower Rate of Subsequent Revision Procedures After Total Shoulder Arthroplasty: A National Analysis.

BACKGROUND: Studies assessing the relationship between surgeon volume and outcomes have shown mixed results, depending on the specific procedure analyzed. This volume relationship has not been well studied in patients undergoing total shoulder arthroplasty (TSA), but it should be, because this procedure is common, expensive, and potentially morbid. QUESTIONS/PURPOSES: We performed this study to assess the association between increasing surgeon volume and decreasing rate of revision at 2 years for (1) anatomic TSA (aTSA) and (2) reverse TSA (rTSA) in the United States. METHODS: In this retrospective study, we used Centers for Medicare and Medicaid Services (CMS) fee-for-service inpatient and outpatient data from 2015 to 2021 to study the association between annual surgeon aTSA and rTSA volume and 2-year revision shoulder procedures after the initial surgery. The CMS database was chosen for this study because it is a national sample and can be used to follow patients over time. We included patients with Diagnosis-related Group code 483 and Current Procedural Terminology code 23472 for TSA (these codes include both aTSA and rTSA). We used International Classification of Diseases, Tenth Revision, procedural codes. Patients who underwent shoulder arthroplasty for fracture (10% [17,524 of 173,242]) were excluded. We studied the variables associated with the subsequent procedure rate through a generalized linear model, controlling for confounders such as patient age, comorbidity risk score, surgeon and hospital volume, surgeon graduation year, hospital size and teaching status, assuming a binomial distribution with the dependent variable being whether an episode had at least one subsequent procedure within 2 years. The regression was fitted with standard errors clustered at the hospital level, combining all TSAs and within the aTSA and rTSA groups, respectively. Hospital and surgeon yearly volumes were calculated by including all TSAs, primary procedure and subsequent, during the study period. Other hospital-level and surgeon-level characteristics were obtained through public files from the CMS. The CMS Hierarchical Condition Category risk score was controlled because it is a measure reflecting the expected future health costs for each patient based on the patient's demographics and chronic illnesses. We then converted regression coefficients to the percentage change in the odds of having a subsequent procedure. RESULTS: After controlling for confounding variables including patient age, comorbidity risk score, surgeon and hospital volume, surgeon graduation year, and hospital size and teaching status, we found that an annual surgeon volume of ≥ 10 aTSAs was associated with a 27% decreased odds of revision within 2 years (95% confidence interval 13% to 39%; p < 0.001), while surgeon volume of ≥ 29 aTSAs was associated with a 33% decreased odds of revision within 2 years (95% CI 18% to 45%; p < 0.001) compared with a volume of fewer than four aTSAs per year. Annual surgeon volume of ≥ 29 rTSAs was associated with a 26% decreased odds of revision within 2 years (95% CI 9% to 39%; p < 0.001). CONCLUSION: Surgeons should consider modalities such as virtual planning software, templating, or enhanced surgeon training to aid lower-volume surgeons who perform aTSA and rTSA. More research is needed to assess the value of these modalities and their relationship with the rates of subsequent revision. LEVEL OF EVIDENCE: Level III, therapeutic study.

The Western Himalayan fir tree ring record of soil moisture in Pakistan since 1855.

Data on historical soil moisture is crucial for assessing and responding to droughts that commonly occur in climate change-affected countries. The Himalayan temperate forests in Pakistan are particularly at risk of climate change. Developing nations lack the means to gather surface soil moisture (SSM) information. Tree rings are one way to bridge this gap. Here, we employed dendrochronological methods on climate-sensitive tree rings from Abies pindrow to reconstruct the SSM in the Western Himalayan mountain region of Pakistan from 1855 to 2020. December (r = 0.41), May (r = 0.40), and June (r = 0.65) SSMs were found to be the limiting factors for A. pindrow growth. However, only the June SSM showed reconstruction possibility (coefficient of efficiency = 0.201 and reduction of error = 0.325). Over the studied period, we found 6 years (wet year) when June SSM was above the threshold of 32.04 (mean + 2 δ) and 1 year (dry year) when June SSM was below the threshold of 21.28 (mean - 2 δ). It was revealed that 1921 and 1917 were the driest and wettest SSM of all time, with means of 19.34 and 36.49, respectively. Our study shows that winter soil moisture is critical for the growing season in the context of climate change. Climate change has broad impacts on tree growth in the Western Himalayas. This study will assist various stakeholders in understanding and managing local and regional climate change.

Emerging Treatment Options for Massive Rotator Cuff Tears: Biologic Tuberoplasty, Balloon Arthroplasty, Anterior Cable Reconstruction, Lower Trapezius Transfer.

There are several emerging treatments for patients with massive rotator cuff tears. Biologic tuberoplasty is still in its infancy but holds promise for improving pain and function by biologically covering a bare tuberosity with a dermal allograft to prevent bone-to-bone contact between the tuberosity and the undersurface of the acromion. Balloon arthroplasty is a technique of widespread interest, with the device recently gaining FDA approval. Anterior cable reconstruction uses the autologous long head of the biceps tendon to reconstruct the anterior cable of the rotator cuff. Tendon transfers, specifically lower trapezius tendon transfer, have now been established as a viable option especially in patients who want to regain active external rotation.

Preoperative prophylactic antibiotics administration does not influence culture yield in revision shoulder arthroplasty.

BACKGROUND: The importance of administrating prophylactic antibiotics prior to a surgical procedure is well established. Given the difficulty in diagnosing shoulder periprosthetic infections, which are more indolent in nature, some advocate holding prophylactic antibiotics prior to obtaining cultures as there is a concern antibiotics may lead to a false negative culture result. The purpose of this study is to determine whether administration of antibiotics prior to obtaining cultures in revision shoulder arthroplasty influences culture yield. METHODS: This was a retrospective analysis of revision shoulder arthroplasty cases performed at a single institution between 2015 and 2021. During the study period, each surgeon had a standardized protocol that dictated whether antibiotics were given or held prior to each revision surgery. Each case was categorized into either a Preculture antibiotic group, if antibiotics were administered prior to incision, or a Postculture antibiotic group if antibiotics were administered after incision and obtaining cultures. The International Consensus Meeting (ICM) scoring criteria provided by the Musculoskeletal Infection Society was used to categorize the probability of periprosthetic joint infection for each case. Culture positivity was calculated as the ratio of positive cultures and total number of cultures obtained. RESULTS: One hundred twenty-four patients met inclusion criteria. There were 48 patients in the Preculture group and 76 patients in the Postculture group. No significant difference in patient demographics or ICM criteria (P = .09) was observed between the 2 groups. With regard to culture positivity, there was no difference between the Preculture antibiotic group and the Postculture antibiotic group (16% vs. 15%, P = .82, confidence interval = 8%-25% vs. 10%-20%, respectively). CONCLUSION: In the setting of revision shoulder arthroplasty, timing of antibiotic administration did not significantly influence culture yield. This study supports the use of prophylactic antibiotics prior to obtaining cultures in revision shoulder arthroplasty.

Anatomic shoulder arthroplasty in Walch type C glenoid deformity: mid- to long-term outcomes.

BACKGROUND: Hypoplastic glenoid morphology in the setting of glenohumeral osteoarthritis is a rare yet complex surgical problem. Treatment of this patient population with anatomic total shoulder arthroplasty (aTSA) remains controversial. Furthermore, there is no gold-standard approach, with limited guidance for surgeons on the need for glenoid version correction in the setting of a dysplastic glenoid. The purpose of this study was to evaluate mid- to long-term outcomes and reoperation rates of aTSA for the treatment of primary glenohumeral osteoarthritis with Walch type C glenoid deformity. METHODS: This observational, retrospective cohort study identified patients with a Walch type C glenoid who underwent aTSA at 2 institutions between 2007 and 2016. Patients were contacted to complete updated patient-reported outcome measures at a minimum of 5.5 years postoperatively. The outcome measures collected included the American Shoulder and Elbow Surgeons (ASES) score and Single Assessment Numeric Evaluation (SANE) score. Secondary outcomes included any additional surgical procedures on the operative shoulder, patient satisfaction, and willingness to undergo aTSA again. RESULTS: In total, 30 patients met the inclusion criteria, of whom 26 (86.7%) were able to be contacted to undergo final outcome evaluations. The mean age at the time of surgery was 61.3 years (range, 40.9-75.5 years), and 20 patients (76.9%) were men. The mean follow-up period was 8.5 years (range, 5.5-11.3 years) after surgery. Treatment was performed with an augmented component in 9 patients and with a standard component in 17. Of the 17 patients with non-augmented components, 9 underwent partial correction with asymmetrical reaming, 3 received a mini-inset glenoid component, and 2 had an anteriorly offset humeral component. At final follow-up, patients had a mean ASES score of 83.6 ± 16.7, ASES pain score of 24.7 ± 20.8, SANE score of 80.4 ± 20.9, and patient satisfaction rate of 84.1%. No statistically significant differences in any outcome measure were observed between patients with augmented glenoid components and those with non-augmented glenoid components. One revision to reverse shoulder arthroplasty was performed for instability at 7 years postoperatively after a traumatic dislocation. All patients reported that they would be willing to undergo the same surgical procedure again. DISCUSSION: Despite variance in glenoid reconstructive approach, aTSA provides satisfactory and sustained improvements in patient-reported outcomes in patients with glenoid dysplasia and primary glenohumeral osteoarthritis with a low revision rate at a mean of 8.5 years. Anatomic shoulder arthroplasty should remain a surgical option in patients with Walch type C glenoid deformity.

Impact of the COVID-19 pandemic on shoulder arthroplasty: surgical trends and postoperative care pathway analysis.

BACKGROUND: COVID-19 triggered disruption in the conventional care pathways for many orthopedic procedures. The current study aims to quantify the impact of the COVID-19 pandemic on shoulder arthroplasty hospital surgical volume, trends in surgical case distribution, length of hospitalization, posthospital disposition, and 30-day readmission rates. METHODS: This study queried all Medicare (100% sample) fee-for-service beneficiaries who underwent a shoulder arthroplasty procedure (Diagnosis-Related Group code 483, Current Procedural Terminology code 23472) from January 1, 2019, to December 18, 2020. Fracture cases were separated from nonfracture cases, which were further subdivided into anatomic or reverse arthroplasty. Volume per 1000 Medicare beneficiaries was calculated from April to December 2020 and compared to the same months in 2019. Length of stay (LOS), discharged-home rate, and 30-day readmission for the same period were obtained. The yearly difference adjusted for age, sex, race (white vs. nonwhite), Centers for Medicare & Medicaid Services Hierarchical Condition Category risk score, month fixed effects, and Core-Based Statistical Area fixed effects, with standard errors clustered at the provider level, was calculated using a multivariate analysis (P < .05). RESULTS: A total of 49,412 and 41,554 total shoulder arthroplasty (TSA) cases were observed April through December for 2019 and 2020, respectively. There was an overall decrease in shoulder arthroplasty volume per 1000 Medicare beneficiaries by 14% (19% reduction in anatomic TSA, 13% reduction in reverse shoulder arthroplasty, and 3% reduction in fracture cases). LOS for all shoulder arthroplasty cases decreased by 16% (-0.27 days, P < .001) when adjusted for confounders. There was a 5% increase in the discharged-home rate (88.0% to 92.7%, P < .001), which was most prominent in fracture cases, with a 20% increase in discharged-home cases (65.0% to 73.4%, P < .001). There was no significant change in 30-day hospital readmission rates overall (P = .20) or when broken down by individual procedures. CONCLUSIONS: There was an overall decrease in shoulder arthroplasty volume per 1000 Medicare beneficiaries by 14% during the COVID-19 pandemic. A decrease in LOS and increase in the discharged-home rates was also observed with no significant change in 30-day hospital readmission, indicating that a shift toward an outpatient surgical model can be performed safely and efficiently and has the potential to provide value.

Ball-Milling-Enabled Reactivity of Manganese Metal*.

Efforts to generate organomanganese reagents under ball-milling conditions have led to the serendipitous discovery that manganese metal can mediate the reductive dimerization of arylidene malonates. The newly uncovered process has been optimized and its mechanism explored using CV measurements, radical trapping experiments, EPR spectroscopy, and solution control reactions. This unique reactivity can also be translated to solution whereupon pre-milling of the manganese is required.

Clinical Management of Osteoporotic Fractures.

PURPOSE OF REVIEW: This review examines recent literature regarding the clinical management of fragility fractures, provides insight into new practice patterns, and discusses controversies in current management. RECENT FINDINGS: There are declining rates of osteoporosis management following initial fragility fracture. Management of osteoporotic fractures via a multidisciplinary team reduces secondary fracture incidence and improves overall osteoporotic care. Anabolic agents (abaloparatide and teriparatide) are effective adjuvants to fracture repair, and have shown positive results in cases of re-fracture in spite of medical management (i.e., bisphosphonates). For AO 31-A1 and A2 intertrochanteric hip fractures (non-reverse obliquity), no clinical advantage of intramedullary fixation over the sliding hip screw (SHS) has been proven; SHS is more cost-effective. As fragility fracture incidence continues to rise, orthopedic surgeons must play a more central role in the care of osteoporotic patients. Initiation of pharmacologic intervention is key to preventing subsequent fragility fractures, and may play a supportive role in initial fracture healing. While the media bombards patients with complications of medical therapy (atypical femur fractures, osteonecrosis of jaw, myocardial infarction), providers need to understand and communicate the low incidence of these complications compared with consequences of not initiating medical therapy.

Six centuries of Upper Indus Basin streamflow variability and its climatic drivers.

Our understanding of the full range of natural variability in streamflow, including how modern flow compares to the past, is poorly understood for the Upper Indus Basin (UIB) because of short instrumental gauge records. To help address this challenge, we use Hierarchical Bayesian Regression (HBR) with partial pooling to develop six centuries long (1394-2008 C.E.) streamflow reconstructions at three UIB gauges (Doyian, Gilgit, and Kachora), concurrently demonstrating that HBR can be used to reconstruct short records with interspersed missing data. At one gauge (Partab Bridge), with a longer instrumental record (47 years), we develop reconstructions using both Bayesian Regression (BR) and the more conventionally used Principal Components Regression (PCR). The reconstructions produced by PCR and BR at Partab Bridge are nearly identical and yield comparable reconstruction skill statistics, highlighting that the resulting tree-ring reconstruction of streamflow is not dependent on the choice of statistical method. Reconstructions at all four reconstructions indicate flow levels in the 1990s were higher than mean flow for the past six centuries. While streamflow appears most sensitive to accumulated winter (January-March) precipitation and summer (MJJAS) temperature, with warm summers contributing to high flow through increased melt of snow and glaciers, shifts in winter precipitation and summer temperatures cannot explain the anomalously high flow during the 1990s. Regardless, the sensitivity of streamflow to summer temperatures suggests that projected warming may increase streamflow in coming decades, though long-term water risk will additionally depend on changes in snowfall and glacial mass balance.