Development of a machine learning algorithm to predict the residual cognitive reserve index.

Elucidating the mechanisms by which late-life neurodegeneration causes cognitive decline requires understanding why some individuals are more resilient than others to the effects of brain change on cognition (cognitive reserve). Currently, there is no way of measuring cognitive reserve that is valid (e.g. capable of moderating brain-cognition associations), widely accessible (e.g. does not require neuroimaging and large sample sizes), and able to provide insight into resilience-promoting mechanisms. To address these limitations, this study sought to determine whether a machine learning approach to combining standard clinical variables could (i) predict a residual-based cognitive reserve criterion standard and (ii) prospectively moderate brain-cognition associations. In a training sample combining data from the University of California (UC) Davis and the Alzheimer's Disease Neuroimaging Initiative-2 (ADNI-2) cohort (N = 1665), we operationalized cognitive reserve using an MRI-based residual approach. An eXtreme Gradient Boosting machine learning algorithm was trained to predict this residual reserve index (RRI) using three models: Minimal (basic clinical data, such as age, education, anthropometrics, and blood pressure), Extended (Minimal model plus cognitive screening, word reading, and depression measures), and Full [Extended model plus Clinical Dementia Rating (CDR) and Everyday Cognition (ECog) scale]. External validation was performed in an independent sample of ADNI 1/3/GO participants (N = 1640), which examined whether the effects of brain change on cognitive change were moderated by the machine learning models' cognitive reserve estimates. The three machine learning models differed in their accuracy and validity. The Minimal model did not correlate strongly with the criterion standard (r = 0.23) and did not moderate the effects of brain change on cognitive change. In contrast, the Extended and Full models were modestly correlated with the criterion standard (r = 0.49 and 0.54, respectively) and prospectively moderated longitudinal brain-cognition associations, outperforming other cognitive reserve proxies (education, word reading). The primary difference between the Minimal model-which did not perform well as a measure of cognitive reserve-and the Extended and Full models-which demonstrated good accuracy and validity-is the lack of cognitive performance and informant-report data in the Minimal model. This suggests that basic clinical variables like anthropometrics, vital signs, and demographics are not sufficient for estimating cognitive reserve. Rather, the most accurate and valid estimates of cognitive reserve were obtained when cognitive performance data-ideally augmented by informant-reported functioning-was used. These results indicate that a dynamic and accessible proxy for cognitive reserve can be generated for individuals without neuroimaging data and gives some insight into factors that may promote resilience.

Revision Total Hip Arthroplasty: Evaluating the Utility of the Geriatric Nutritional Risk Index as a Risk Stratification Tool.

Background: This study investigates the association between the Geriatric Nutritional Risk Index (GNRI), a measure of malnutrition risk, and 30-day postoperative complications following revision total hip arthroplasty (rTHA). Methods: The American College of Surgeons National Surgical Quality Improvement Program database was queried for all patients ≥65 who underwent aseptic rTHA between 2015 and 2021. The final study population (n = 7119) was divided into 3 groups based on preoperative GNRI: normal/reference (GNRI >98) (n = 4342), moderate malnutrition (92 ≤ GNRI ≤98) (n = 1367), and severe malnutrition (GNRI <92) (n = 1410). Multivariate logistic regression analysis was conducted to investigate the association between preoperative GNRI and 30-day postoperative complications. Results: After controlling for significant covariates, the risk of experiencing any postoperative complications was significantly higher with both moderate (odds ratio [OR] 2.08, P < .001) and severe malnutrition (OR 8.79, P < .001). Specifically, moderate malnutrition was independently and significantly associated with deep vein thrombosis (OR 1.01, P = .044), blood transfusions (OR 1.78, P < .001), nonhome discharge (OR 1.83, P < .001), readmission (OR 1.27, P = .035), length of stay >2 days (OR 1.98, P < .001), and periprosthetic fracture (OR 1.54, P = .020). Severe malnutrition was independently and significantly associated with sepsis (OR 3.67, P < .001), septic shock (OR 3.75, P = .002), pneumonia (OR 2.73, P < .001), urinary tract infection (OR 2.04, P = .002), deep vein thrombosis (OR 1.01, P = .001), pulmonary embolism (OR 2.47, P = .019), acute renal failure (OR 8.44, P = .011), blood transfusions (OR 2.78, P < .001), surgical site infection (OR 2.59, P < .001), nonhome discharge (OR 3.36, P < .001), readmission (OR 1.69, P < .001), unplanned reoperation (OR 1.97, P < .001), length of stay >2 days (OR 5.41, P < .001), periprosthetic fractures (OR 1.61, P = .015), and mortality (OR 2.63, P < .001). Conclusions: Malnutrition has strong predictive value for short-term postoperative complications and has potential as an adjunctive risk stratification tool for geriatric patients undergoing rTHA.

Electrical neuromodulation for the treatment of chronic pain: derivation of the intrinsic barriers, outcomes and considerations of the sustainability of implantable spinal cord stimulation therapies.

INTRODUCTION: For over 60 years, spinal cord stimulation has endured as a therapy through innovation and novel developments. Current practice of neuromodulation requires proper patient selection, risk mitigation and use of innovation. However, there are tangible and intangible challenges in physiology, clinical science and within society. AREAS COVERED: We provide a narrative discussion regarding novel topics in the field especially over the last decade. We highlight the challenges in the patient care setting including selection, as well as economic and socioeconomic challenges. Physician training challenges in neuromodulation is explored as well as other factors related to the use of neuromodulation such as novel indications and economics. We also discuss the concepts of technology and healthcare data. EXPERT OPINION: Patient safety and durable outcomes are the mainstay goal for neuromodulation. Substantial work is needed to assimilate data for larger and more relevant studies reflecting a population. Big data and global interconnectivity efforts provide substantial opportunity to reinvent our scientific approach, data analysis and its management to maximize outcomes and minimize risk. As improvements in data analysis become the standard of innovation and physician training meets demand, we expect to see an expansion of novel indications and its use in broader cohorts.

Stereoselective C-B and C-H Bonds Functionalization of PolyBorylated Alkenes.

Alkenes are fundamental functional groups which feature in various materials and bioactive molecules; however, efficient divergent strategies for their stereodefined synthesis are difficult. In this regard, numerous synthetic methodologies have been developed to construct carbon-carbon bonds with regio- and stereoselectivity, enabling the predictable and efficient synthesis of stereodefined alkenes. In fact, an appealing alternative approach for accessing challenging stereodefined alkenes molecular frameworks could involve the sequential selective activation and cross-coupling of strong bonds instead of conventional C-C bond formation. In this study, we introduce a series of programmed site- and stereoselective strategies that capitalizes on the versatile reactivity of readily accessible polymetalloid alkenes (i.e. polyborylated alkenes), through a tandem cross-coupling reaction, which is catalyzed by an organometallic Rh-complex to produce complex molecular scaffolds. By merging selective C-B and remote C-H bond functionalization, we achieve the in-situ generation of polyfunctional C(sp2)-nucleophilic intermediates. These species can be further modified by selective coupling reactions with various C-based electrophiles, enabling the formation of C(sp2)-C(sp3) bond for the generation of even more complex molecular architectures using the readily available starting polyborylated-alkenes. Mechanistic and computational studies have provided insight into the origins of the stereoselectivities and C-H activation via a 1,4-Rh migration process.

The McCusker Subjective Cognitive Impairment Inventory (McSCI): a novel measure of perceived cognitive decline.

BACKGROUND: Subjective cognitive decline (SCD), i.e. self/other-reported concerns on one's cognitive functioning without objective evidence of significant decline, is an indicator of dementia risk. There is little consensus on reliability and validity of the available SCD measures. Therefore, introducing a novel and psychometrically sound measure of SCD is timely. OBJECTIVE: The psychometric properties of a new SCD measure, the McCusker Subjective Cognitive Impairment Inventory-Self-Report (McSCI-S), are reported. METHODS: Through review of previously published measures as well as our clinical and research data on people with SCD, we developed a 46-item self-report questionnaire to assess concerns on six cognitive domains, namely, memory, language, orientation, attention and concentration, visuoconstruction abilities and executive function. The McSCI-S was examined in a cohort of 526 participants using factor analysis, item response theory analysis and receiver operating characteristic (ROC) curve. RESULTS: A unidimensional model provided acceptable fit (CFI = 0.94, TLI = 0.94, RMSEA [90% CI] = 0.052 [.049, 0.055], WRMR = 1.45). The McSCI-S internal consistency was excellent (.96). A cut-off score of ≥24 is proposed to identify participants with SCDs. Higher McSCI-S scores were associated with poorer general cognition, episodic verbal memory, executive function and greater memory complaints and depressive scores (P < .001), controlling for age, sex and education. CONCLUSIONS: Excellent reliability and construct validity suggest the McSCI-S estimates SCDs with acceptable accuracy while capturing self-reported concerns for various cognitive domains. The psychometric analysis indicated that this measure can be used in cohort studies as well as on individual, clinical settings to assess SCDs.

Dynamics of nanocluster aerosol in the indoor atmosphere during gas cooking.

Nanocluster aerosol (NCA: particles in the size range of 1-3 nm) are a critically important, yet understudied, class of atmospheric aerosol particles. NCA efficiently deposit in the human respiratory system and can translocate to vital organs. Due to their high surface area-to-mass ratios, NCA are associated with a heightened propensity for bioactivity and toxicity. Despite the human health relevance of NCA, little is known regarding the prevalence of NCA in indoor environments where people spend the majority of their time. In this study, we quantify the formation and transformation of indoor atmospheric NCA down to 1 nm via high-resolution online nanoparticle measurements during propane gas cooking in a residential building. We observed a substantial pool of sub-1.5 nm NCA in the indoor atmosphere during cooking periods, with aerosol number concentrations often dominated by the newly formed NCA. Indoor atmospheric NCA emission factors can reach up to ∼1016 NCA/kg-fuel during propane gas cooking and can exceed those for vehicles with gasoline and diesel engines. Such high emissions of combustion-derived indoor NCA can result in substantial NCA respiratory exposures and dose rates for children and adults, significantly exceeding that for outdoor traffic-associated NCA. Combustion-derived indoor NCA undergo unique size-dependent physical transformations, strongly influenced by particle coagulation and condensation of low-volatility cooking vapors. We show that indoor atmospheric NCA need to be measured directly and cannot be predicted using conventional indoor air pollution markers such as PM2.5 mass concentrations and NO x (NO + NO2) mixing ratios.

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.

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, 2018-004354-21.).

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.

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.

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).

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.

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.

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. 2024;47(4):e181-e187.].

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.