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BACKGROUND: Despite the pivotal role of clinical trials in advancing orthopaedic oncology knowledge and treatment strategies, the persistent issues of trial discontinuation and nonpublication are significant problems. This study conducted an analysis examining clinical trial discontinuation rates, associations between intervention types and discontinuation/nonpublication, and the role of funding, enrollment size, and their implications for trial success and completion. METHODS: This study, conducted on May 1, 2023, utilized a cross-sectional design to comprehensively analyze phase 3 and 4 randomized controlled trials within the realm of orthopaedic oncology. We specifically incorporated Phase 3 and 4 trials as they are designed to evaluate prolonged outcomes in human subjects and are more likely to reach publication. Study characteristics of interest included the intervention utilized in the clinical trial, presence of funding, whether the trial was published, completed, and trial enrollment size. The investigation involved an examination of ClinicalTrials.gov, a prominent online repository of clinical trial data managed by the National Library of Medicine of the USA. Descriptive statistics and multivariate logistic regressions were used to determine statistical significance. RESULTS: Among the cohort of 130 trials, 19.2% were prematurely discontinued. Completion rates varied based on intervention type; 111 pharmaceutical trials demonstrated a completion rate of 83.8%, whereas 19 non-pharmaceutical trials exhibited a completion rate of 8.0% (P

Background Orthopaedic surgery has the lowest number of full-time faculty positions held by women, at 19%, with endowed chairs among the most coveted and advantageous. We examined the characteristics of endowed professors from the US top 100 orthopaedic academic centers and highest-funded musculoskeletal (MSK) researchers to determine if gender is associated with endowed professorship. Additionally, we sought to determine if gender is associated with increased NIH funding for top-performing musculoskeletal researchers.  Methods Our primary study group included the top 100 orthopaedic academic centers defined by US News World Report and Doximitys rankings. Our secondary study group examined the top MSK researchers, defined as principal investigators, who received >$400,000 in annual NIH funding from 2018 to 2021. Orthopaedic departments included MSK researchers and subspecialties within orthopaedics and medicine. Publicly available sources were used to compile institutional, gender, H-index, citation number, and subspecialty data on endowed professors; statistical comparisons were calculated. Results Within the top 100 orthopaedic academic departments, 4674 faculty were identified. Seven hundred and thirty-three (15.68%) were identified as women, 3941 as men (84.32%). One hundred and ninety-four held endowed professorships; 13 were awarded to women (6.7%), and 185 (95.3%) were awarded to men, with a significant odds ratio (OR) of 2.95, favoring men. For MSK researchers, the OR increases to 11.4. Arthroplasty and sports had the highest numbers of endowments. Significant differences in H-index, publications, and graduation year were identified between men and women for top MSK researchers and orthopaedic-trained surgeons; however, these differences disappeared when considering heterogenous orthopaedic departments that included medicine subspecialties, plastic surgery, hand surgery, and neurosurgery. Additional gender differences were observed in endowment names, with awards commemorating 51.5% men, 7.2% women, and 34% families or groups. Conclusion Gender inequities at the endowment level are substantial, and there are very few women in musculoskeletal medicine to achieve endowments. Differences in H-index, publications, and graduation year between men and women MSK researchers and orthopaedic-trained surgeons, but not combined orthopaedic, PM&R, and medical subspecialty departments, suggest unique challenges in orthopaedic surgery environments and histories that may contribute to endowment disparity. Gender was not found to be associated with funding bias for top-performing musculoskeletal researchers.

Mechanical stimuli, such as stretch, shear stress, or compression, activate a range of biomolecular responses through cellular mechanotransduction. In the nervous system, studies on mechanical stress have highlighted key pathophysiological mechanisms underlying traumatic injury and neurodegenerative diseases. However, the biomolecular pathways triggered by mechanical stimuli in the nervous system has not been fully explored, especially compared to other body systems. This gap in knowledge may be due to the wide variety of methods and definitions used in research. Additionally, as mechanical stimulation techniques such as ultrasound and electromagnetic stimulation are increasingly utilized in psychological and neurorehabilitation treatments, it is vital to understand the underlying biological mechanisms in order to develop accurate pathophysiological models and enhance therapeutic interventions. This review aims to summarize the cellular signaling pathways activated by various mechanical and electromagnetic stimuli with a particular focus on the mammalian nervous system. Furthermore, we briefly discuss potential cellular mechanosensors involved in these processes.

IntroductionThe purpose of this study is to provide a state-of-the-art review regarding risk factors for perioperative complications in adult spinal deformity (ASD) surgery. The review includes levels of evidence for risk factors associated with complications in ASD surgery.MethodsUsing the PubMed database, we searched for complications, risk factors, and adult spinal deformity. The included publications were assessed for level of evidence as described in clinical practice guidelines published by the North American Spine Society, with summary statements generated for each risk factor (Bono et al. in Spine J 9:1046-1051, 2009).ResultsFrailty had good evidence (Grade A) as a risk for complications in ASD patients. Fair evidence (Grade B) was assigned for bone quality, smoking, hyperglycemia and diabetes, nutritional status, immunosuppression/steroid use, cardiovascular disease, pulmonary disease, and renal disease. Indeterminate evidence (Grade I) was assigned for pre-operative cognitive function, mental health, social support, and opioid utilization.ConclusionsIdentification of risk factors for perioperative complications in ASD surgery is a priority for empowering informed choices for patients and surgeons and managing patient expectations. Risk factors with grade A and B evidence should be identified prior to elective surgery and modified to reduce the risk of perioperative complications.

BackgroundSocial determinants of health (SDOH), have been demonstrated to significantly impact health outcomes in spine patients. There may be interaction between opioid use and these factors in spine surgical patients. We aimed to evaluate the social determinants of health (SDOH) which are associated with perioperative opioid use among lumbar spine patients.MethodsThis retrospective cohort study included patients undergoing spine surgery for lumbar degeneration in 2019. Opioid use was determined based on prescription records from the electronic medical records. Preoperative opioid users (OU) were compared with opioid-naïve patients regarding SDOH including demographics like age and race, and clinical data such as activity and tobacco use. Demographics and surgical data, including age, comorbidities, surgical invasiveness, and other variables were also collected from the records. Multivariate logistic regression was used for analysis of these factors.ResultsNinety-eight patients were opioid-naïve and 90 used opioids preoperatively. All OU had ≥3 months of use, had more prior spine surgeries (1.07 vs. 0.44, p

PurposeTo identify independent risk factors, including the Risk Assessment and Prediction Tool (RAPT) score, associated with extended length of stay (eLOS) and non-home discharge following elective multi-level instrumented spine fusion operations for diagnosis of adult spinal deformity (ASD) and lumbar degenerative pathology.MethodsAdults who underwent multi-level ([Formula: see text] segments) instrumented spine fusions for ASD and lumbar degenerative pathology at a single institution (2016-2021) were reviewed. Presence of a pre-operative RAPT score was used as an inclusion criterion. Excluded were patients who underwent non-elective operations, revisions, operations for trauma, malignancy, and/or infections. Outcomes were eLOS (> 7 days) and discharge location (home vs. non-home). Predictor variables included demographics, comorbidities, operative information, Surgical Invasiveness Index (SII), and RAPT score. Fisher's exact test was used for univariate analysis, and significant variables were implemented in multivariate binary logistic regression, with generation of 95% percent confidence intervals (CI), odds ratios (OR), and p-values.ResultsIncluded for analysis were 355 patients. Post-operatively, 36.6% (n = 130) had eLOS and 53.2% (n = 189) had a non-home discharge. Risk factors significant for a non-home discharge were older age (> 70 years), SII > 36, pre-op RAPT  20, RAPT

Mechanical stimuli, such as stretch, shear stress, or compression, activate a range of biomolecular responses through cellular mechanotransduction. In the nervous system, studies on mechanical stress have highlighted key pathophysiological mechanisms underlying traumatic injury and neurodegenerative diseases. However, the biomolecular pathways triggered by mechanical stimuli in the nervous system has not been fully explored, especially compared to other body systems. This gap in knowledge may be due to the wide variety of methods and definitions used in research. Additionally, as mechanical stimulation techniques such as ultrasound and electromagnetic stimulation are increasingly utilized in psychological and neurorehabilitation treatments, it is vital to understand the underlying biological mechanisms in order to develop accurate pathophysiological models and enhance therapeutic interventions. This review aims to summarize the cellular signaling pathways activated by various mechanical and electromagnetic stimuli with a particular focus on the mammalian nervous system. Furthermore, we briefly discuss potential cellular mechanosensors involved in these processes. [ABSTRACT FROM AUTHOR]

Amibegron, a β3‐adrenergic receptor (B3AR) agonist, has recently been shown to provide therapeutic effects for chronic rotator cuff (RC) tears by inducing the expression of uncoupling protein 1 (UCP‐1), a marker of brown fat, in fibroadipogenic progenitors (FAPs). However, it remains to be seen if these beneficial effects hold true with age and in older, more clinically relevant populations. This study seeks to understand the impacts of aging on the efficacy of amibegron to treat chronic RC tears. Young (4‐month‐old) and aged (33‐month‐old) C57BL/6 mice underwent a RC injury procedure with delayed repair (DR). Mice were equally randomized to receive amibegron or dimethyl sulfoxide (DMSO) treatments after repair. Functional ability was measured at baseline and 6‐weeks after DR. Wet muscle weight and histology of injured and contralateral supraspinatus were also analyzed 6‐weeks post‐DR. For in vitro histology and real‐time quantitative PCR experiments, FAPs were isolated from young and aged mice via fluorescence‐activated cell sorting. Young and aged FAPs were treated with amibegron or DMSO either immediately after seeding (early exposure) or 8‐days after seeding (late exposure). In vitro results showed that amibegron‐mediated FAP UCP‐1 expression decreases with age. In vivo data demonstrated that aged mice have a decreased responsiveness to amibegron and decreased propensity for intramuscular FAP UCP‐1 expression. Further, delayed amibegron treatment with RC repair did not lead to improvements in muscle atrophy and functional outcomes. Our findings demonstrate that age and the timing of interventions play a critical role in FAP‐targeted therapeutics for chronic injuries. [ABSTRACT FROM AUTHOR]

K2P potassium channels are known to be modulated by volatile anesthetic (VA) drugs and play important roles in clinically relevant effects that accompany general anesthesia. Here, we utilize a photoaffinity analog of the VA isoflurane to identify a VA-binding site in the TREK1 K2P channel. The functional importance of the identified site was validated by mutagenesis and biochemical modification. Molecular dynamics simulations of TREK1 in the presence of VA found multiple neighboring residues on TREK1 TM2, TM3, and TM4 that contribute to anesthetic binding. The identified VA-binding region contains residues that play roles in the mechanisms by which heat, mechanical stretch, and pharmacological modulators alter TREK1 channel activity and overlaps with positions found to modulate TASK K2P channel VA sensitivity. Our findings define molecular contacts that mediate VA binding to TREK1 channels and suggest a mechanistic basis to explain how K2P channels are modulated by VAs. [ABSTRACT FROM AUTHOR]

Mechanical stimuli, such as stretch, shear stress, or compression, activate a range of biomolecular responses through cellular mechanotransduction. In the nervous system, studies on mechanical stress have highlighted key pathophysiological mechanisms underlying traumatic injury and neurodegenerative diseases. However, the biomolecular pathways triggered by mechanical stimuli in the nervous system has not been fully explored, especially compared to other body systems. This gap in knowledge may be due to the wide variety of methods and definitions used in research. Additionally, as mechanical stimulation techniques such as ultrasound and electromagnetic stimulation are increasingly utilized in psychological and neurorehabilitation treatments, it is vital to understand the underlying biological mechanisms in order to develop accurate pathophysiological models and enhance therapeutic interventions. This review aims to summarize the cellular signaling pathways activated by various mechanical and electromagnetic stimuli with a particular focus on the mammalian nervous system. Furthermore, we briefly discuss potential cellular mechanosensors involved in these processes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ryu, Wague, Liu, Feeley, Ferguson and Morioka.)