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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.
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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.
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Background: Total shoulder arthroplasty (TSA) in patients with rheumatoid arthritis (RA) can present unique challenges. The aim of this study was to compare both systemic and joint-related postoperative complications in patients undergoing primary TSA with RA versus those with primary osteoarthritis (OA). Methods: Using the TriNetX database, Current Procedural Terminology and International Classification of Diseases, 10th edition codes were used to identify patients who underwent primary TSA. Patients were categorized into two cohorts: RA and OA. After 1:1 propensity score matching, postoperative systemic complications within 90 days following primary TSA and joint-related complications within 5 years following anatomic TSA (aTSA) and reverse shoulder arthroplasty (RSA) were compared. Results: After propensity score matching, the RA and OA cohorts each consisted of 8,523 patients. Within 90 days postoperation, RA patients had a significantly higher risk of total complications, deep surgical site infection, wound dehiscence, pneumonia, myocardial infarction, acute renal failure, urinary tract infection, mortality, and readmission compared to the OA cohort. RA patients had a significantly greater risk of periprosthetic joint infection and prosthetic dislocation within 5 years following aTSA and RSA, and a greater risk of scapular fractures following RSA. Among RA patients, RSA had a significantly higher risk of prosthetic dislocation, scapular fractures, and revision compared to aTSA. Conclusions: Following TSA, RA patients should be considered at higher risk of systemic and joint-related complications compared to patients with primary OA. Knowledge of the risk profile of RA patients undergoing TSA is essential for appropriate patient counseling and education. Level of evidence: III.
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CASE: A 71-year-old female patient presented with severe glenoid bone loss and deformity after 2 subsequent failed arthroplasty procedures because of baseplate failures. The patients then underwent a conversion from reverse shoulder arthroplasty to hemiarthroplasty, while using a distal radius allograft to augment the deformed glenoid. At the 2-year follow-up, the patient reported minimal pain and satisfactory outcomes. CONCLUSION: This case presents the distal radius as a potentially useful allograft option for augmenting severe glenoid bone loss in the setting of revision shoulder arthroplasty.
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Aloinjertos , Artroplastía de Reemplazo de Hombro , Radio (Anatomía) , Reoperación , Humanos , Femenino , Anciano , Radio (Anatomía)/cirugía , Radio (Anatomía)/trasplante , Trasplante Óseo/métodos , Articulación del Hombro/cirugía , Articulación del Hombro/diagnóstico por imagenRESUMEN
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.
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Antineoplásicos , Proliferación Celular , Química Clic , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores de Proteínas Quinasas , Proteínas Serina-Treonina Quinasas , Triazoles , Humanos , Triazoles/química , Triazoles/farmacología , Triazoles/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Estructura Molecular , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/metabolismo , Línea Celular Tumoral , Nitrilos/química , Nitrilos/farmacología , Nitrilos/síntesis químicaRESUMEN
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.
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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 post-discharge, 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 (LASSO) 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 (AUC) of 0.70, and 16 were selected to predict any adverse postoperative outcome (AUC=0.75). The LASSO 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.
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OBJECTIVE: This study aims to evaluate published clinical trials of ramucirumab to assess the risk/benefit profile and burden over time for patients. BACKGROUND: The burden of oncologic drug development on patients paired with increasing clinical trial failure rates emphasizes the need for reform of drug development. Identifying and addressing patterns of excess burden can guide policy, ensure evidence-based protections for trial participants, and improve medical decision-making. METHODS: On May 25, 2023 a literature search was performed on Pubmed/MEDLINE, Embase, Cochrane CENTRAL, and ClinicalTrials.gov for clinical trials using ramucirumab as monotherapy or in combination with other interventions for cancer treatment. Authors screened titles and abstracts for potential inclusion in a masked, duplicate fashion. Following data screening, data was extracted in a masked, duplicate fashion. Trials were classified as positive when meeting their primary endpoint and safety, negative or indeterminate. RESULTS: Ramucirumab was initially approved for gastric cancer but has since been tested in 20 cancers outside of its FDA approved indications. In our analysis of ramucirumab trials, there were a total of 10,936 participants and 10,303 adverse events reported. Gains in overall survival and progression-free survival for patients were 1.5 and 1.2 months, respectively. FDA-approved indications have reported more positive outcomes in comparison to off-label indications. CONCLUSION: We found that FDA-approved indications for ramucirumab had better efficacy outcomes than non-approved indications. However, a concerning number of adverse events were observed across all trials assessed. Participants in ramucirumab randomized controlled trials saw meager gains in overall survival when evaluated against a comparison group. Clinicians should carefully weigh the risks associated with ramucirumab therapy given its toxicity burden and poor survival gains.
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Anticuerpos Monoclonales Humanizados , Ensayos Clínicos como Asunto , Desarrollo de Medicamentos , Ramucirumab , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Medición de Riesgo , Neoplasias/tratamiento farmacológico , Neoplasias/mortalidad , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversosRESUMEN
INTRODUCTION: The diagnosis of neovascular age-related macular degeneration (nAMD), the leading cause of visual impairment in the developed world, relies on the interpretation of various imaging tests of the retina. These include invasive angiographic methods, such as Fundus Fluorescein Angiography (FFA) and, on occasion, Indocyanine-Green Angiography (ICGA). Newer, non-invasive imaging modalities, predominately Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCTA), have drastically transformed the diagnostic approach to nAMD. The aim of this study is to undertake a comprehensive diagnostic accuracy assessment of the various imaging modalities used in clinical practice for the diagnosis of nAMD (OCT, OCTA, FFA and, when a variant of nAMD called Polypoidal Choroidal Vasculopathy is suspected, ICGA) both alone and in various combinations. METHODS AND ANALYSIS: This is a non-inferiority, prospective, randomised diagnostic accuracy study of 1067 participants. Participants are patients with clinical features consistent with nAMD who present to a National Health Service secondary care ophthalmology unit in the UK. Patients will undergo OCT as per standard practice and those with suspicious features of nAMD on OCT will be approached for participation in the study. Patients who agree to take part will also undergo both OCTA and FFA (and ICGA if indicated). Interpretation of the imaging tests will be undertaken by clinicians at recruitment sites. A randomised design was selected to avoid bias from consecutive review of all imaging tests by the same clinician. The primary outcome of the study will be the difference in sensitivity and specificity between OCT+OCTA and OCT+FFA (±ICGA) for nAMD detection as interpreted by clinicians at recruitment sites. ETHICS AND DISSEMINATION: The study has been approved by the South Central-Oxford B Research Ethics Committee with reference number 21/SC/0412.Dissemination of study results will involve peer-review publications, presentations at major national and international scientific conferences. TRIAL REGISTRATION NUMBER: ISRCTN18313457.
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Angiografía con Fluoresceína , Tomografía de Coherencia Óptica , Humanos , Neovascularización Coroidal/diagnóstico por imagen , Neovascularización Coroidal/diagnóstico , Angiografía con Fluoresceína/métodos , Degeneración Macular/diagnóstico por imagen , Estudios Multicéntricos como Asunto , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Tomografía de Coherencia Óptica/métodos , Reino Unido , Degeneración Macular Húmeda/diagnóstico por imagen , Degeneración Macular Húmeda/diagnósticoRESUMEN
Purpose: Minimal clinically important difference (MCID), substantial clinical benefit (SCB), and patient acceptable symptomatic state (PASS) serve as metrics to gauge orthopedic treatment efficacy based on anchoring questions that do not account for a patient's satisfaction with their surgical outcome. This study evaluates if reaching MCID, SCB, or PASS values for American Shoulder and Elbow Surgeons score (ASES), Single Alpha Numeric Evaluation (SANE), Simple Shoulder Test (SST), and Visual Analog Score (VAS) for pain following arthroscopic rotator cuff repair (RCR) correlates with overall patient satisfaction. Methods: This was a single-institution, retrospective study of patients who underwent RCR from 2015 to 2019. Pre-operative and 2 year postoperative ASES, SANE, SST, and VAS scores were recorded. Patients underwent a survey to assess: (1) what is your overall satisfaction with your surgical outcome? (scale 1 to 10); (2) if you could go back in time, would you undergo this operation again? (yes/no); (3) for the same condition, would you recommend this operation to a friend or family member? (yes/no). Spearman correlation coefficients were run to assess relationship between reaching MCID, SCB, or PASS and satisfaction. Results: Ninety-two patients were included. Mean preoperative ASES was 51.1 ± 16.9, SANE was 43.3 ± 20.9, SST was 5.4 ± 2.9, and VAS was 4.6 ± 2.1. Mean 2 year ASES was 83.9 ± 18.5, SANE was 81.7 ± 27.0, SST was 9.8 ± 3.2, and VAS was 1.4 ± 1.9. Mean patient satisfaction was 9.0 ± 1.9; 89 (96.7%) patients would undergo surgery again and recommend surgery. Correlation for reaching PASS for SANE and satisfaction was moderate. Correlation coefficients were very weak for all other outcome metrics. Conclusions: Reaching MCID, SCB, and PASS in ASES, SANE, SST, or VAS following RCR did not correlate with a patient's overall satisfaction or willingness to undergo surgery again or recommend surgery. Further investigation into the statistical credibility and overall clinical value of MCID, SCB, and PASS is necessary.
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Background: Dementia is a recognized complication of atrial fibrillation (AF). Oral anticoagulant (OAC) therapy can potentially be protective against this complication. Methods: A comprehensive search of MEDLINE and Embase for comparative observational studies reporting the efficacy of OAC therapy for the incidence of dementia in patients with AF was conducted from its inception until March 2023. Studies that had patients with prior use of OAC or with a previous history of dementia were excluded. Results: A total of 22 studies were included in this review involving 617,204 participants. The pooled analysis revealed that OAC therapy, including direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs), was associated with a reduced incidence of dementia in AF patients. Specifically, compared to non-OAC treatment, OACs demonstrated a significant reduction in dementia incidence (HR 0.68, 95 % CI [0.58, 0.80], p < 0.00001), with similar findings observed for DOACs (HR 0.69, 95 % CI [0.51, 0.94], p = 0.02) and VKAs (HR 0.73, 95 % CI [0.56, 0.95], p = 0.02). The comparison of DOAC vs VKA revealed that DOACs are associated with reduced risk of dementia (HR 0.87, 95 % CI [0.79, 0.96], p = 0.004). Conclusion: Our SR and meta-analysis showed that the use of OAC therapy is associated with a reduced risk of dementia in individuals with AF. However, our results are limited by the potential influence of confounding bias and significant heterogeneity in the analyses.
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AIM: Statin therapy is considered the gold standard for treating hypercholesterolemia. This updated meta-analysis aims to compare the efficacy and safety of a low/moderate-intensity statin in combination with ezetimibe compared with high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (ASCVD). METHODS: A systematic search of two databases (PubMed and Cochrane CENTRAL) was conducted from inception to January 2023 and a total of 21 randomized clinical trials (RCTs) were identified and included in the analysis. Data were pooled using Hedges's g and a Mantel-Haenszel random-effects model to derive standard mean differences (SMDs) and 95% confidence intervals (Cis). The primary outcome studied was the effect of these treatments on lipid parameters and safety events. RESULTS: The results revealed that combination therapy was more effective in reducing low-density lipoprotein cholesterol (LDL-C) levels (SMD= - 0.41; CI - 0.63 to - 0.19; P = 0.0002). There was no significant change in the levels of high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglyceride (TG), high-sensitivity C-reactive protein (hs-CRP), Apo A1, or Apo B. The safety of these treatments was assessed by the following markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatine phosphokinase (CK), and a significant difference was only observed in CK (SMD: - 0.81; CI - 1.52 to - 0.10; P = 0.02). CONCLUSION: This meta-analysis demonstrated that the use of low/moderate-intensity statin combination therapy significantly reduced LDL-C levels compared with high-intensity statin monotherapy, making it preferable for patients with related risks. However, further trials are encouraged to evaluate potential adverse effects associated with combined therapy.
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Anticolesterolemiantes , Aterosclerosis , Quimioterapia Combinada , Ezetimiba , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , Anticolesterolemiantes/administración & dosificación , Anticolesterolemiantes/efectos adversos , Anticolesterolemiantes/uso terapéutico , Aterosclerosis/tratamiento farmacológico , Enfermedades Cardiovasculares , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Ezetimiba/administración & dosificación , Ezetimiba/uso terapéutico , Ezetimiba/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipercolesterolemia/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Background: To effectively counsel patients prior to shoulder arthroplasty, surgeons should understand the overall life trajectory and life expectancy of patients in the context of the patient's shoulder pathology and medical comorbidities. Such an understanding can influence both operative and nonoperative decision-making and implant choices. This study evaluated 5-year mortality following shoulder arthroplasty in patients ≥65 years old and identified associated risk factors. Methods: We utilized Centers for Medicare & Medicaid Services Fee-for-Service inpatient and outpatient claims data to investigate the 5-year mortality rate following shoulder arthroplasty procedures performed from 2014 to 2016. The impact of patient demographics, including fracture diagnosis, year fixed effects, and state fixed effects; patient comorbidities; and hospital-level characteristics on 5-year mortality rates were assessed with use of a Cox proportional hazards regression model. A p value of <0.05 was considered significant. Results: A total of 108,667 shoulder arthroplasty cases (96,104 nonfracture and 12,563 fracture) were examined. The cohort was 62.7% female and 5.8% non-White and had a mean age at surgery of 74.3 years. The mean 5-year mortality rate was 16.6% across all shoulder arthroplasty cases, 14.9% for nonfracture cases, and 29.9% for fracture cases. The trend toward higher mortality in the fracture group compared with the nonfracture group was sustained throughout the 5-year postoperative period, with a fracture diagnosis being associated with a hazard ratio of 1.63 for mortality (p < 0.001). Medical comorbidities were associated with an increased risk of mortality, with liver disease bearing the highest hazard ratio (3.07; p < 0.001), followed by chronic kidney disease (2.59; p < 0.001), chronic obstructive pulmonary disease (1.92; p < 0.001), and congestive heart failure (1.90; p < 0.001). Conclusions: The mean 5-year mortality following shoulder arthroplasty was 16.6%. Patients with a fracture diagnosis had a significantly higher 5-year mortality risk (29.9%) than those with a nonfracture diagnosis (14.9%). Medical comorbidities had the greatest impact on mortality risk, with chronic liver and kidney disease being the most noteworthy. This novel longer-term data can help with patient education and risk stratification prior to undergoing shoulder replacement. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
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INTRODUCTION: Total joint arthroplasties (TJAs) have recently been shifting toward outpatient arthroplasty. This study aims to explore recent trends in outpatient total joint arthroplasty (TJA) procedures and examine whether patients with a higher comorbidity burden are undergoing outpatient arthroplasty. METHODS: Medicare fee-for-service claims were screened for patients who underwent total hip, knee, or shoulder arthroplasty procedures between January 2019 and December 2022. The procedure was considered to be outpatient if the patient was discharged on the same date of the procedure. The Hierarchical Condition Category Score (HCC) and the Charlson Comorbidity Index (CCI) scores were used to assess patient comorbidity burden. Patient adverse outcomes included all-cause hospital readmission, mortality, and postoperative complications. Logistic regression analyses were used to evaluate if higher HCC/CCI scores were associated with adverse patient outcomes. RESULTS: A total of 69,520, 116,411, and 41,922 respective total knee, hip, and shoulder arthroplasties were identified, respectively. Despite earlier removal from the inpatient-only list, outpatient knee and hip surgical volume did not markedly increase until the pandemic started. By 2022Q4, 16%, 23%, and 36% of hip, knee, and shoulder arthroplasties were discharged on the same day of surgery, respectively. Both HCC and CCI risk scores in outpatients increased over time ( P < 0.001). DISCUSSION: TJA procedures are shifting toward outpatient surgery over time, largely driven by the COVID-19 pandemic. TJA outpatients' HCC and CCI risk scores increased over this same period, and additional research to determine the effects of this should be pursued. LEVEL OF EVIDENCE: Level III, therapeutic retrospective cohort study.
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Procedimientos Quirúrgicos Ambulatorios , Medicare , Humanos , Estados Unidos/epidemiología , Estudios Retrospectivos , Anciano , Masculino , Femenino , Procedimientos Quirúrgicos Ambulatorios/tendencias , Procedimientos Quirúrgicos Ambulatorios/estadística & datos numéricos , Anciano de 80 o más Años , Complicaciones Posoperatorias/epidemiología , Artroplastía de Reemplazo de Hombro , Artroplastia de Reemplazo de Cadera/estadística & datos numéricos , Artroplastia de Reemplazo de Rodilla/estadística & datos numéricos , COVID-19/epidemiología , Comorbilidad , Readmisión del Paciente/estadística & datos numéricos , Artroplastia de Reemplazo/estadística & datos numéricos , Artroplastia de Reemplazo/tendenciasRESUMEN
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.
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Vacuna BCG , Inmunoterapia , Microambiente Tumoral , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/inmunología , Neoplasias de la Vejiga Urinaria/terapia , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Animales , Microambiente Tumoral/inmunología , Ratones , Vacuna BCG/inmunología , Vacuna BCG/administración & dosificación , Vacuna BCG/uso terapéutico , Inmunoterapia/métodos , Femenino , Administración Intravesical , Ratones Endogámicos C57BL , Linfocitos T Citotóxicos/inmunología , Humanos , Modelos Animales de Enfermedad , Inmunidad Innata/inmunología , Línea Celular Tumoral , Memoria Inmunológica/inmunología , Células Supresoras de Origen Mieloide/inmunología , Inmunidad EntrenadaRESUMEN
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.
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Artroplastía de Reemplazo de Hombro , Ensayo de Materiales , Polietilenos , Diseño de Prótesis , Falla de Prótesis , Prótesis de Hombro , Vitamina E , Humanos , Artroplastía de Reemplazo de Hombro/métodos , Fenómenos Biomecánicos , Tamaño de la Partícula , Osteólisis/etiología , Osteólisis/prevención & control , Articulación del Hombro/cirugíaRESUMEN
BACKGROUND: Distal tibial allograft (DTA) reconstruction for glenoid bone loss is nonanatomic, as it does not match the glenoid radius of curvature (ROC) in the anterior-posterior (AP) plane. The dorsal articular portion of the distal radius has not been previously described as an allograft reconstruction option for glenoid bone loss. PURPOSE: To evaluate distal radius fresh-frozen allograft (DRA) as a potential match for glenoid reconstruction. STUDY DESIGN: Controlled laboratory study. METHODS: Eighteen fresh-frozen human cadaveric specimens-including 6 shoulder, 6 wrist, and 6 tibia specimens-were used. The ROC and the graft length were measured in the superior-inferior (SI) plane. A 30% defect was created in all glenoid specimens, and both DTAs and DRAs were harvested to assess graft fit after fixation. Computed tomography analysis was used to assess bony ROC and bone mineral density (BMD). RESULTS: The cadaveric specimens had a mean age of 77 years. The mean SI glenoid length was 39.7 mm compared with 36.8 mm for the DRA and 30 mm for the DTA. The ROC in the SI plane was 29 ± 5.3 mm for the glenoid, 37.8 ± 4.9 mm for the DRA, and 24 ± 3.7 mm for the DTA. In the AP plane, the ROC was 39.6 ± 6.6 mm for the glenoid, 30.4 ± 18.6 mm for the DRA, and 126.3 ± 9.5 mm for the DTA. On computed tomography analysis, the ROC in the SI plane was 30.4 ± 1.5 mm for the glenoid, 30.3 ± 5.6 mm for the DRA, and 24.5 ± 9.4 mm for the DTA. In the AP plane, the ROC was 30.8 ± 2 mm for the glenoid, 19.1 ± 2.3 mm for the DRA, and 46.7 ± 21.7 mm for the DTA. The BMD was 226.3 ± 79 Hounsfield units (HU) for the glenoid, 228.5 ± 94.7 HU for the DRA, 235 ± 96.2 HU for the coracoid process, and 235.1 ± 84.6 HU for the DTA. CONCLUSION: Compared with the DTA, the DRA had a greater mean graft length in the SI plane, providing utilization in cases of larger bony defects; the DRA has a more acute ROC in the AP plane (closer to that of the glenoid), providing a greater potential buttress to anterior humeral translation. Compared with currently utilized grafts, the DRA BMD was not significantly diminished. This study presents the DRA as a novel allograft reconstruction option in the setting of anterior glenoid bone loss; further biomechanical and clinical investigation is indicated.
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Inestabilidad de la Articulación , Articulación del Hombro , Humanos , Anciano , Articulación del Hombro/cirugía , Radio (Anatomía)/cirugía , Inestabilidad de la Articulación/cirugía , Aloinjertos , CadáverRESUMEN
Researchers from multiple disciplines have studied the simulation of actions through motor imagery, action observation, or their combination. Procedures used in these studies vary considerably between research groups, and no standardized approach to reporting experimental protocols has been proposed. This has led to under-reporting of critical details, impairing the assessment, replication, synthesis, and potential clinical translation of effects. We provide an overview of issues related to the reporting of information in action simulation studies, and discuss the benefits of standardized reporting. We propose a series of checklists that identify key details of research protocols to include when reporting action simulation studies. Each checklist comprises A) essential methodological details, B) essential details that are relevant to a specific mode of action simulation, and C) further points that may be useful on a case-by-case basis. We anticipate that the use of these guidelines will improve the understanding, reproduction, and synthesis of studies using action simulation, and enhance the translation of research using motor imagery and action observation to applied and clinical settings.
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Imágenes en Psicoterapia , Imaginación , Humanos , Imágenes en Psicoterapia/métodos , PoaceaeRESUMEN
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.
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Artroplastía de Reemplazo de Hombro , Pacientes Internos , Anciano , Humanos , Estados Unidos/epidemiología , Pacientes Ambulatorios , Artroplastía de Reemplazo de Hombro/efectos adversos , Centers for Medicare and Medicaid Services, U.S. , Pandemias , Medicare , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Readmisión del Paciente , Estudios RetrospectivosRESUMEN
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.