Belantamab Mafodotin, Pomalidomide, and Dexamethasone in Multiple Myeloma.

BACKGROUND: Triplet or quadruplet therapies incorporating proteasome inhibitors, immunomodulators, and anti-CD38 antibodies have led to prolonged survival among patients with newly diagnosed multiple myeloma; however, most patients have a relapse. Frontline lenalidomide therapy has increased the number of patients with lenalidomide-refractory disease at the time of the first relapse. METHODS: In this phase 3, randomized, open-label trial, we evaluated belantamab mafodotin, pomalidomide, and dexamethasone (BPd), as compared with pomalidomide, bortezomib, and dexamethasone (PVd), in lenalidomide-exposed patients who had relapsed or refractory myeloma after at least one line of therapy. The primary end point was progression-free survival. Disease response and safety were also assessed. RESULTS: A total of 302 patients underwent randomization; 155 were assigned to the BPd group, and 147 to the PVd group. At a median follow-up of 21.8 months (range, <0.1 to 39.2), the 12-month estimated progression-free survival with BPd was 71% (95% confidence interval [CI], 63 to 78), as compared with 51% (95% CI, 42 to 60) with PVd (hazard ratio for disease progression or death, 0.52; 95% CI, 0.37 to 0.73; P<0.001). Data on overall survival were immature. The percentage of patients with a response to treatment (partial response or better) was 77% (95% CI, 70 to 84) in the BPd group and 72% (95% CI, 64 to 79) in the PVd group; 40% (95% CI, 32 to 48) and 16% (95% CI, 11 to 23), respectively, had a complete response or better. Grade 3 or higher adverse events occurred in 94% of the patients in the BPd group and 76% of those in the PVd group. Ocular events occurred in 89% of the patients who received BPd (grade 3 or 4 in 43%) and 30% of those who received PVd (grade 3 or 4 in 2%); ocular events in the BPd group were managed with belantamab mafodotin dose modification. Ocular events led to treatment discontinuation in 9% of the patients in the BPd group and in no patients in the PVd group. CONCLUSIONS: Among lenalidomide-exposed patients with relapsed or refractory myeloma, BPd conferred a significantly greater benefit than PVd with respect to progression-free survival, as well as deeper, more durable responses. Ocular events were common but were controllable by belantamab mafodotin dose modification. (Funded by GSK; DREAMM-8 ClinicalTrials.gov number, NCT04484623; EudraCT number, 2018-00434-21.).

Risks of Reoperation in Surgically Treated Fractures of the Proximal Phalanx.

Purpose: The objective of this study was to determine the risk factors and the rate of reoperation after closed reduction percutaneous pinning (CRPP) of isolated closed single-digit proximal phalanx fractures. Methods: A retrospective cohort study was conducted for patients who underwent CRPP of non-thumb closed proximal phalanx fractures between 2010 and 2020 at two level-I trauma centers and two community teaching hospitals. Demographics, fracture, and treatment characteristics were collected. The primary outcome measure was reoperation. Secondary outcome measures were complication and reoperation specifically for digital stiffness. Results: Of the 115 patients who underwent surgical treatment, 46 patients (40.0%) had a complication and 13 patients (11.3%) underwent reoperation at a mean of 6.7 months-most of which (84.6%) were for digital stiffness. Conclusions: Surgeons and patients may be aware that CRPP of closed extra-articular proximal phalanx fractures carries considerable rates of complication and reoperation. Type of study/level of evidence: Therapeutic III.

Jaw Thrust: A Simple Predictor of Success in Mandibular Distraction Osteogenesis.

BACKGROUND: The hypoplastic mandible in the congenital condition Pierre Robin sequence (PRS) displaces the base of the tongue posteriorly, which results in upper airway obstruction (UAO) that can potentially be corrected with mandibular distraction osteogenesis (MDO). Jaw thrust (JT) is routinely performed during evaluation of the airway; similar to MDO, it projects the mandible and tongue anteriorly to open the airway. The authors demonstrate that JT can be used as a criterion to predict successful MDO outcomes in infants with PRS. METHODS: The study was a single-center, retrospective chart review of infants diagnosed with PRS between 2016 and 2023. Data regarding their demographics, comorbid diagnoses, JT success, airway anomalies, laryngeal grade of view, apnea-hypopnea index, and perioperative course were statistically analyzed. RESULTS: Of the 16 patients included in the study, 11 had successful relief of their airway obstruction with JT and proceeded with MDO. The unsuccessful JT group had significantly greater proportions of females, birth prematurity, gastrostomies, tracheostomies, and longer hospital stays. In the successful JT group, both the mean laryngeal grade of view (P=0.029) and mean apnea-hypopnea index (P=0.025) improved significantly post-MDO. Post-MDO tracheostomy was also avoided in all but 1 patient who was not previously tracheostomized. CONCLUSIONS: There is no widely accepted algorithm to guide craniofacial surgeons on the optimal intervention for relieving UAO in infants with PRS. In our institutional experience, patients whose preoperative JT relieved UAO also successfully relieved UAO with MDO. In patients with PRS, JT may be a useful criterion for selecting appropriate candidates for MDO.

Potassium-Alkali-Enriched Diet, Hypertension, and Proteinuria following Uninephrectomy.

BACKGROUND: Losing or donating a kidney is associated with risks of developing hypertension and albuminuria. Few studies address mechanisms or interventions. We investigate potential benefits of a K+- alkali-enriched diet and the mechanisms underlying proteinuria. METHODS: Male Sprague Dawley rats were fed either a 2% NaCl + 0.95% KCl diet (HNa-LK) or a 0.74% NaCl + 3% K+-alkali diet (HK-alk) for 3 wk prior to uninephrectomy then maintained on respective diets for 12 wk. Blood pressure (by tail-cuff), urine, blood and kidney proteins were analyzed Pre- and Post-uninephrectomy. RESULTS: Pre-uninephrectomy, HK-alk vs. HNa-LK fed rats exhibited similar blood pressures and plasma [K+], [Na+], but lower proximal (NHE3, NBCe1, NaPi2) and higher distal (NCC, ENaC, pendrin) transporter abundance, a pattern facilitating K+ and HCO3- secretion. Post-uninephrectomy, single nephron GFR rose 50% and Li+ clearance doubled with both diets; in HK-alk vs HNa-LK: the rise in blood pressure was less and ammoniagenesis was lower, abundance of proximal tubule transporters remained lower, ENaC-α fell and NCCp rose consistent with K+ conservation. Post-uninephrectomy, independent of diet, albuminuria increased 8-fold and abundance of endocytic receptors was reduced (megalin by 44%, dab2 by 25-35%) and KIM-1 was increased. CONCLUSIONS: The K-alkali-enriched diet blunted post-uninephrectomy hypertension and facilitated acid clearance by suppressing proximal Na+ transporters and increasing K+ -alkali secretion. Further, uninephrectomy associated proteinuria could be attributed, at least in part, to elevated SNGFR coupled to downregulation of megalin which reduced fractional protein endocytosis and Vmax.

Current Status of Cardiac Regenerative Therapy Using Induced Pluripotent Stem Cells.

Heart failure (HF) is a life-threatening disorder and is treated by drug therapies and surgical interventions such as heart transplantation and left ventricular assist device (LVAD). However, these treatments can lack effectiveness in the long term and are associated with issues such as donor shortage in heart transplantation, and infection, stroke, or gastrointestinal bleeding in LVADs. Therefore, alternative therapeutic strategies are still needed. In this respect, stem cell therapy has been introduced for the treatment of HF and numerous preclinical and clinical studies are employing a range of stem cell varieties. These stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have been shown to improve cardiac function and attenuate left ventricular remodeling. IPSCs, which have a capacity for unlimited proliferation and differentiation into cardiomyocytes, are a promising cell source for myocardial regeneration therapy. In this review, we discuss the following topics: (1) what are iPSCs; (2) the limitations and solutions for the translation of iPSC-CMs practically; and (3) the current therapeutic clinical trials.

Predicting operative outcomes of total shoulder arthroplasty using the model for end-stage liver disease score.

Background: The aim of this study was to assess the efficacy of the Model for End-Stage Liver Disease (MELD) score in predicting postoperative complications following total shoulder arthroplasty (TSA). Methods: The American College of Surgeons National Surgical Quality Improvement database was queried for all patients who underwent TSA between 2015 and 2019. The study population was subsequently classified into two categories: those with a MELD score ≥ 10 and those with a MELD score < 10. A total of 5265 patients undergoing TSA between 2015 and 2019 were included in this study. Among these, 4690 (89.1%) patients had a MELD score ≥ 10, while 575 (10.9%) patients had a MELD score < 10. Postoperative complications within 30 days of the TSA were collected. Multivariate logistic regression analysis was conducted to explore the correlation between a MELD score ≥ 10 and postoperative complications. The anchor based optimal cutoff was calculated by receiver operating characteristic analysis to determine the MELD score cutoff that most accurately predicts a specific complication. Youden's index (J) determined the optimal cutoff point calculation for the maximum sensitivity and specificity; these were deemed to be "acceptable" if the area under curve (AUC) was greater than 0.7 and "excellent" if greater than 0.8. Results: Multivariate regression analysis found a MELD score ≥ 10 to be independently associated with higher rates of reoperation (OR, 2.08; P = .013), cardiac complications (OR, 3.37; P = .030), renal complications (OR, 7.72; P = .020), bleeding transfusions (OR, 3.23; P < .001), and nonhome discharge (OR, 1.75; P < .001). The receiver operating characteristic analysis showed that AUC for a MELD score cutoff of 7.61 as a predictor of renal complications was 0.87 (excellent) with sensitivity of 100.0% and specificity of 70.0%. AUC for a MELD score cutoff of 7.76 as a predictor of mortality was 0.76 (acceptable) with sensitivity of 81.8% and specificity of 71.0%. Conclusion: A MELD score ≥ 10 was correlated with high rates of reoperation, cardiac complications, renal complications, bleeding transfusions, and nonhome discharge following TSA. MELD score cutoffs of 7.61 and 7.76 were effective in predicting renal complications and mortality, respectively.

Cumulative effect of chronic dehydration and age on postoperative complications after total shoulder arthroplasty.

Background: Dehydration is a modifiable risk factor that should be optimized prior to all surgical procedures. The aim of this study was to determine the effects of dehydration on postoperative complications following total shoulder arthroplasty (TSA). Methods: The American College of Surgeons National Surgical Quality Improvement database was queried for all patients who underwent TSA between 2015 and 2019 and a total of 16,993 patients were included in this study. The study population was subsequently classified into 3 categories: 8498 (50.0%) nondehydrated patients with blood urea nitrogen/creatinine (BUN/Cr) < 20, 4908 (28.9%) moderately dehydrated patients with 20 ≤ BUN/Cr ≤ 25, and 3587 (21.1%) severely dehydrated patients with 25 < BUN/Cr. A subgroup analysis involving only elderly patients aged > 65 years and normalized gender-adjusted Cr values was also performed. Postoperative complications within 30 days of the TSA were collected. Multivariate logistic regression analysis was conducted to explore the correlation between dehydration and postoperative complications. Results: Adjusted multivariate logistic regression analysis showed that the severely dehydrated cohort had a greater risk of postoperative transfusion, mortality, nonhome discharge, and increased length of stay (all P < .05). The moderately dehydrated cohort had a greater risk of wound dehiscence (P = .044). Among the elderly, severely dehydrated patients had a greater risk of cardiac complications, postoperative transfusion, mortality, nonhome discharge, and increased length of stay (all P < .05). Finally, the elderly moderately dehydrated cohort had a greater risk of postoperative transfusion and nonhome discharge (all P < .05). Conclusion: BUN/Cr ratio is an important preoperative diagnostic tool to identify at-risk dehydrated patients. Providers should optimize dehydration to prevent complications, decrease costs, and improve discharge planning.

The Neuropsychological Assessment Battery Driving Scenes Test in a Dementia Clinic.

OBJECTIVE: In dementia research, the Driving Scenes test from the Neuropsychological Assessment Battery has been shown to relate to memory, dementia diagnosis, and functional impairment. The aim of the current study was to examine Driving Scenes and its component scores, and their relationships with cognition and daily functioning, in a mixed dementia clinic sample. METHOD: One hundred U.S. military veterans between the ages of 55 and 88 were administered a full neuropsychological protocol that included Driving Scenes. RESULTS: The Driving Scenes score and its subscores were strongly related to memory skills, and there were additional subscore associations with language and visuospatial functions. Driving Scenes uniquely predicted reported bill payment difficulties and tendency to get lost while driving, which were not predicted by other performances across cognitive domains. CONCLUSION: Driving Scenes is a clinically and functionally relevant measure of memory. Although the Driving Scenes total score remains useful in dementia evaluations, component scores and error scores contribute additional practical information.

Preoperative Dehydration Is an Underrecognized Modifiable Risk Factor in Total Hip Arthroplasty.

Dehydration is an overlooked modifiable risk factor that should be optimized prior to elective total hip arthroplasty (THA) to reduce postoperative complications and inpatient costs. All primary THA from 2005 - 2019 were queried from the National Surgical Quality Improvement Program database, and patients were compared based on dehydration status: blood urea nitrogen (BUN): creatinine ratio (Cr) (BUN/Cr) < 20 (nondehydrated), 20 ≤ BUN/Cr ≤ 25 (moderately dehydrated), 25 < BUN/Cr (severely dehydrated). A subgroup analysis involving only elderly patients > 65 years and normalized gender-adjusted Cr values was also performed. The analysis included 212,452 patients who underwent THA. Adjusted multivariate logistic regression analysis showed that the severely dehydrated cohort had a greater risk of overall complications, postoperative anemia requiring transfusion, nonhome discharge, and increased length of stay (all p < 0.01). Among the elderly, dehydrated patients had a greater risk of postoperative transfusion, cardiac complications, and nonhome discharge (all p < 0.01). BUN/Cr > 20 is an important preoperative diagnostic tool to identify at-risk dehydrated patients. Providers should optimize dehydration to prevent complications, decrease costs, and improve discharge planning. (Journal of Surgical Orthopaedic Advances 33(1):017-025, 2024).

Evaluating Prescriber Adherence to a Standardized Postoperative Opioid Prescription Protocol for Cubital Tunnel Surgery.

Purpose: Concerns regarding the ongoing opioid epidemic have led to the implementation of standardized postoperative opioid-prescribing protocols for many common hand surgical procedures. This study investigated patient- and procedure-specific factors affecting adherence to a standardized postoperative opioid-prescribing protocol after cubital tunnel surgery. Methods: A retrospective review of patients who underwent primary cubital tunnel surgery within one academic medical system between October 1, 2016 (after the implementation of a standardized postoperative opioid-prescribing protocol) and March 1, 2020 was performed. Patients aged <18 years or with a history of revision surgery, prior traumatic ulnar nerve injury, additional concurrent surgical procedures, or a surgeon not participating in the protocol were excluded. Patient demographics, comorbidities, prior opioid history, and surgical variables were recorded. The primary outcome was adherence to the standardized postoperative opioid-prescribing protocol. A bivariate statistical analysis was performed. Results: Ninety-eight patients were included. The median initial postoperative prescription amount was 75 morphine equivalent units (100% of protocol target) for 78 patients (80% of cohort) who underwent in situ decompression and 75 morphine equivalent units (50% of protocol target) for 20 patients (20% of cohort) who underwent decompression with ulnar nerve transposition. Forty-nine percent of initial opioid prescriptions adhered to protocol, compared with 26% below target and 26% above target. In the bivariate analysis, recent opioid prescriptions within 3 months preoperatively were associated with improved prescriber protocol adherence; longer tourniquet time and anterior transposition were associated with prescriptions below target, and in situ decompression was associated with prescriptions above target. Conclusions: Variation in postoperative opioid-prescribing patterns persists despite the implementation of a standardized postoperative opioid-prescribing protocol. Recent opioid prescriptions were associated with protocol adherence, possibly reflecting increased provider vigilance in this patient population. Differing target prescription amounts for in situ decompression versus decompression with anterior transposition may be unnecessary. Type of study/level of evidence: Therapeutic IV.

Factors Associated With Episode of Care Adverse Events After Humerus Nonunion Repair.

BACKGROUND: Humeral nonunions have devastating negative effects on patients' upper extremity function and health-related quality of life. The objective of this study was to identify factors independently associated with 30-day complication, hospital readmission, and reoperation after surgical treatment of humeral nonunions. MATERIALS AND METHODS: A retrospective case-control study was performed using the American College of Surgeons National Surgical Quality Improvement Program database by querying the Current Procedural Terminology codes for patients who underwent humeral nonunion repair from 2011 to 2020. The study outcomes were 30-day complication, hospital readmission, and reoperation. RESULTS: Of the 1306 patients in our cohort, 135 patients (10%) developed a complication, 66 patients (5%) were readmitted to the hospital, and 44 patients (3%) underwent reoperation during the 30-day postoperative period. Multivariable logistic regression analysis showed that older age, longer operative time, partially dependent functional status, congestive heart failure, bleeding disorder, and contaminated wound classification were associated with 30-day complication after humeral nonunion repair. Older age and disseminated cancer were associated with 30-day reoperation after humeral nonunion repair. Disseminated cancer was associated with 30-day readmission after humeral nonunion repair. CONCLUSION: Using a large database over a recent 10-year period, we identified demographic and comorbid factors independently associated with episode of care adverse events after humeral nonunion repair. Patients 50 years or older had approximately three times the incidence of complications, readmissions, and reoperations in the first month after humeral nonunion repair compared with patients younger than 50 years. Our findings are relevant for preoperative risk stratification and counseling. [Orthopedics. 202x;4x(x):xx-xx.].

Rare variant associations with birth weight identify genes involved in adipose tissue regulation, placental function and insulin-like growth factor signalling.

Investigating the genetic factors influencing human birth weight may lead to biological insights into fetal growth and long-term health. Genome-wide association studies of birth weight have highlighted associated variants in more than 200 regions of the genome, but the causal genes are mostly unknown. Rare genetic variants with robust evidence of association are more likely to point to causal genes, but to date, only a few rare variants are known to influence birth weight. We aimed to identify genes that harbour rare variants that impact birth weight when carried by either the fetus or the mother, by analysing whole exome sequence data in UK Biobank participants. We annotated rare (minor allele frequency <0.1%) protein-truncating or high impact missense variants on whole exome sequence data in up to 234,675 participants with data on their own birth weight (fetal variants), and up to 181,883 mothers who reported the birth weight of their first child (maternal variants). Variants within each gene were collapsed to perform gene burden tests and for each associated gene, we compared the observed fetal and maternal effects. We identified 8 genes with evidence of rare fetal variant effects on birth weight, of which 2 also showed maternal effects. One additional gene showed evidence of maternal effects only. We observed 10/11 directionally concordant associations in an independent sample of up to 45,622 individuals (sign test P=0.01). Of the genes identified, IGF1R and PAPPA2 (fetal and maternal-acting) have known roles in insulin-like growth factor bioavailability and signalling. PPARG, INHBE and ACVR1C (all fetal-acting) have known roles in adipose tissue regulation and rare variants in the latter two also showed associations with favourable adiposity patterns in adults. We highlight the dual role of PPARG in both adipocyte differentiation and placental angiogenesis. NOS3, NRK, and ADAMTS8 (fetal and maternal-acting) have been implicated in both placental function and hypertension. Analysis of rare coding variants has identified regulators of fetal adipose tissue and fetoplacental angiogenesis as determinants of birth weight, as well as further evidence for the role of insulin-like growth factors.

Impacts of economic factors influencing net returns of beef feedlot heifers administered two implant programs and fed for differing days-on-feed from pooled randomized controlled trials.

The objective of this research was to evaluate the effects of two implant programs and differing days-on-feed (DOF) on net returns of beef feedlot heifers using sensitivity analyses of key economic factors. Crossbred beef heifers [n = 10,583; initial weight 315 kg (± 20.1 SD)] were enrolled across three trials (one Kansas, two Texas feedlot trials). Heifers were blocked by arrival and randomly allocated to one of six pens, resulting in a total of 144 pens and 24 blocks. Pen was randomly assigned to treatment as a 2 × 3 factorial. Implant programs were: IH + 200-Revalor-IH at initial processing, and a terminal implant after approximately 90 DOF (Revalor-200), or, XH-a single implant at initial processing (Revalor-XH). The DOF treatments were: heifers fed to a standard baseline endpoint (BASE) or heifers fed for an additional + 21 or + 42 d beyond BASE. Pen-level partial budgets were used for economic sensitivity analyses, which varied price points of single pricing components with all other components fixed. Variable components were live-fed cattle prices, base carcass prices (i.e., dressed), Choice-Select spread (CS-spread), and feed and yardage prices (FYP). For each, a Low, Mid-Low, Middle, Mid-High, and High price was chosen. Linear mixed models were fit for statistical analyses (α = 0.05). There were no significant two-way interactions (P-values ≥ 0.14). Regardless of the variable component evaluated, XH heifers had poorer net returns than IH + 200 at all prices (P ≤ 0.04). Selling live, the + 21 and (or) + 42 heifers had lower net returns than BASE at every fed cattle price point (P < 0.01). Selling dressed, the + 21 and (or) + 42 heifers had lower returns than BASE at Low, Mid-Low, and Middle fed cattle base prices (P < 0.01); there were no significant DOF differences at Mid-High, or High prices (P ≥ 0.24). Net returns were lower for + 42 than BASE at all CS-spreads (P ≤ 0.03), while BASE and + 21 did not differ significantly. Longer DOF had lower net returns than BASE when selling live at every FYP (P < 0.01) except at the Low price (P = 0.14). Selling dressed, there was no significant effect of DOF at Low or Mid-Low FYP (P ≥ 0.11); conversely, extended DOF had lower net returns than BASE at Middle, Mid-High, and High FYP (P < 0.01). Overall, there was minimal economic evidence to support extending feedlot heifer DOF beyond the BASE endpoint, and when feeding longer, larger reductions in return were observed when marketing live as opposed to dressed.

Programmed Heterocycle Synthesis Using Halomucononitriles as Pyridinimine Precursors.

Herein we report a method to convert primary amines, ubiquitous motifs found in pharmaceutical libraries, to either imidazo[1,2-a]pyridines or 7-alkyl azaindoles in two steps from known compounds. Using halomucononitrile reagents, we can directly access 5-bromo-6-imino-1-alkyl-1,6-dihydropyridine-2-carbonitriles (pyridinimines) in a single step from primary amines (25-93% yield) through the cyclization of transient aminomucononitrile intermediates. We then demonstrate that these compounds can be readily converted to 7-alkylazaindoles using Sonogashira cross-coupling conditions (13 examples, up to 91% yield). Under oxidative conditions, the pyridinimines serve as directing groups for C-H functionalization reactions to afford imidazo[1,2-a]pyridines. We also studied the mechanism of the cyclization event using DFT calculations and propose that this takes place via sequential base-mediated E/Z isomerization and cyclization steps.

The Relationship Between Preoperative International Normalized Ratio and Postoperative Major Bleeding in Total Shoulder Arthroplasty.

INTRODUCTION: This study aimed to assess the relationship between preoperative international normalized ratio (INR) levels and major postoperative bleeding events after total shoulder arthroplasty (TSA). METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried for TSA from 2011 to 2020. A final cohort of 2405 patients with INR within 2 days of surgery were included. Patients were stratified into four groups: INR ≤ 1.0, 1.0 < INR ≤ 1.25, 1.25< INR ≤ 1.5, and INR > 1.5. The primary outcome was bleeding requiring transfusion within 72 hours, and secondary outcome variables included complication, revision surgery, readmission, and hospital stay duration. Multivariable logistic and linear regression analyses adjusted for relevant comorbidities were done. RESULTS: Of the 2,405 patients, 48% had INR ≤ 1.0, 44% had INR > 1.0 to 1.25, 7% had INR > 1.25 to 1.5, and 1% had INR > 1.5. In the adjusted model, 1.0 < INR ≤ 1.25 (OR 1.7, 95% CI 1.176 to 2.459), 1.25 < INR ≤ 1.5 (OR 2.508, 95% CI 1.454 to 4.325), and INR > 1.5 (OR 3.200, 95% CI 1.233 to 8.302) were associated with higher risks of bleeding compared with INR ≤ 1.0. DISCUSSION: The risks of thromboembolism and bleeding lie along a continuum, with higher preoperative INR levels conferring higher postoperative bleeding risks after TSA. Clinicians should use a patient-centered, multidisciplinary approach to balance competing risks.

The significance of subjective mechanical symptoms in rotator cuff pathology.

BACKGROUND: The presence of subjective mechanical symptoms, such as clicking or popping, is common in patients presenting for shoulder pain and dysfunction, with unclear clinical significance. The primary objective of this study was to assess whether subjective mechanical symptoms in the affected shoulder were associated with full-thickness rotator cuff tearing in a consecutive, prospective cohort of patients undergoing shoulder magnetic resonance imaging (MRI) for suspected rotator cuff pathology. METHODS: A prospective cohort study was performed of 100 consecutive patients with suspected rotator cuff tendinopathy and/or tearing who underwent shoulder MRI. The presence of subjective shoulder mechanical symptoms, including clicking or popping, was documented prior to MRI. Indications for MRI included weakness on isolated testing of rotator cuff muscle(s) or symptoms refractory to conservative treatment including at least a 6-week course of physical therapy. The primary outcome variable was the presence of full-thickness rotator cuff tearing; secondary outcome variables included any (full-thickness or partial-thickness) rotator cuff tearing and biceps long head subluxation. Radiographic parameters, including critical shoulder angle, Goutallier grade, tear retraction, and tear size were quantified. One patient was lost to follow-up, and 99 patients completed MRI imaging. RESULTS: In our cohort, 60% of patients reported subjective mechanical symptoms in the affected shoulder. Full-thickness rotator cuff tearing was identified in 42% of patients, any rotator cuff tearing in 69% of patients, and biceps long head subluxation in 14% of patients. Subjective mechanical symptoms were not associated with full-thickness rotator cuff tearing, any rotator cuff tearing, biceps long head subluxation, critical shoulder angle, Goutallier grade, tear size, or tear retraction. Older age was associated with full-thickness and any rotator cuff tearing. As a diagnostic test for full-thickness rotator cuff tearing, subjective shoulder mechanical symptoms has a sensitivity of 64%, a specificity of 44%, and Youden's index of 0.08, consistent with poor diagnostic accuracy. CONCLUSIONS: Subjective mechanical symptoms in the affected shoulder are a common complaint in patients with suspected rotator cuff pathology. Patients may be reassured that a sensation of clicking or popping alone does not necessarily entail structural shoulder derangement.

A multifaceted approach to global health.

World Health Day underscores the scientific community's commitment to achieving health equity for all. It is paramount to eliminate bias in research that has traditionally focused on men, neglecting the specific needs of diverse populations. Innovative clinical trial designs are being developed with more inclusive enrollment. Ensuring equitable access to essential antibiotics, coupled with robust infection prevention and control measures, is vital to safeguarding public health. The pursuit of health equity extends beyond the realm of medicine. Investments in local food production and robust social safety nets are critical for mitigating the effects of climate change on access to healthy diets. Additionally, in times of polycrisis, prioritizing the unique needs of children and empowering community-led healthcare initiatives in conflict zones are essential steps. By taking these actions, we can move closer to realizing everyone's fundamental right to health.

Incretin and glucagon receptor polypharmacology in chronic kidney disease.

Chronic kidney disease is a debilitating condition associated with significant morbidity and mortality. In recent years, the kidney effects of incretin-based therapies, particularly glucagon-like peptide-1 receptor agonists (GLP-1RAs), have garnered substantial interest in the management of type 2 diabetes and obesity. This review delves into the intricate interactions between the kidney, GLP-1RAs, and glucagon, shedding light on their mechanisms of action and potential kidney benefits. Both GLP-1 and glucagon, known for their opposing roles in regulating glucose homeostasis, improve systemic risk factors affecting the kidney, including adiposity, inflammation, oxidative stress, and endothelial function. Additionally, these hormones and their pharmaceutical mimetics may have a direct impact on the kidney. Clinical studies have provided evidence that incretins, including those incorporating glucagon receptor agonism, are likely to exhibit improved kidney outcomes. Although further research is necessary, receptor polypharmacology holds promise for preserving kidney function through eliciting vasodilatory effects, influencing volume and electrolyte handling, and improving systemic risk factors.

Associations between personality and psychological characteristics and cognitive outcomes among older adults.

Prior research has shown that some personality traits are associated with cognitive outcomes and may confirm risk or protection against cognitive decline. The present study expands on previous work to examine the association between a more comprehensive set of psychological characteristics and cognitive performance in a diverse cohort of older adults. We also examine whether controlling for brain atrophy influences the association between psychological characteristics and cognitive function. A total of 157 older adults completed a battery of psychological questionnaires (Openness to Experience, Conscientiousness, Agreeableness, Neuroticism, Extraversion, positive affect, negative affect-sadness, negative affect-anger, sense of purpose, loneliness, grit, and self-efficacy). Cognitive outcomes were measured across multiple domains: episodic memory, semantic memory, executive function, and spatial ability. Baseline brain (MRI) variables included gray matter, hippocampus, and total white matter hyperintensity volume. Parallel process, multilevel models yielded intercept (individual cognitive domain scores) and linear slope (global cognitive change) random effects for the cognitive outcomes. Positive affect (ß = 0.013, SE = 0.005, p = .004) and Openness (ß = 0.018, SE = 0.007, p = .009) were associated with less cognitive change, independent of baseline brain variables and covariates. Greater sadness predicted more cognitive decline when controlling for covariates, but not brain atrophy. A variety of psychological characteristics were associated with the cross-sectional measures of cognition. This study highlights the important impact of positive and negative affect on reducing or enhancing the risk of longitudinal cognitive decline. Such findings are especially important, given the available efficacious interventions that can improve affect. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Risk Factors for Rescue Opioid Prescription After Cubital Tunnel Surgery.

BACKGROUND: Concerns regarding the ongoing opioid epidemic have led to heightened scrutiny of postoperative opioid prescribing patterns for common orthopedic surgical procedures. This study investigated patient- and procedure-specific risk factors for additional postoperative opioid rescue prescriptions following ambulatory cubital tunnel surgery. METHODS: A retrospective review was performed of patients who underwent cubital tunnel surgery at 2 academic medical centers between June 1, 2015 and March 1, 2020. Patient demographics, comorbidities, prior opioid history, and surgical variables were recorded. The primary outcome was postoperative rescue opioid prescription. Univariate and bivariate statistical analyses were performed. RESULTS: Two hundred seventy-four patients were included, of whom 171 (62%) underwent in situ ulnar nerve decompression and 103 (38%) underwent ulnar nerve decompression with anterior transposition. The median postoperative opioid prescription amount was 90 morphine equivalent units (MEU) for the total cohort, 77.5 MEU for in situ ulnar nerve decompression, and 112.5 MEU for ulnar nerve decompression with transposition. Twenty-two patients (8%) required additional rescue opioid prescriptions postoperatively. Female sex, fibromyalgia, chronic opioid use, chronic pain diagnosis, and recent opioid were associated with the need for additional postoperative rescue opioid prescriptions. CONCLUSIONS: While most patients do not require additional rescue opioid prescriptions after cubital tunnel surgery, chronic pain patients and patients with pain sensitivity syndromes are at risk for requiring additional rescue opioid prescriptions. For these high-risk patients, preoperative collaboration of a multidisciplinary team may be beneficial for developing a perioperative pain management plan that is both safe and effective.