Deciphering the Molecular Dance: Exploring the Dynamic Interplay Between Mouse Insulin B9-23 Peptides and their Variants.

Type 1 diabetes results from the autoimmune destruction of pancreatic insulin-producing ß-cells, primarily targeted by autoreactive T cells that recognize insulin B9-23 peptides as antigens. Using drift tube ion mobility spectrometry-mass spectrometry, transmission electron microscopy, and two-dimensional infrared spectroscopy, we characterized mouse insulin 1 B9-23 (Ins1 B9-23), insulin 2 B9-23 (Ins2 B9-23), along with two of their mutants, Ins2 B9-23 Y16A and Ins2 B9-23 C19S. Our findings indicate that Ins1 B9-23 and the Ins2 Y16A mutant exhibit rapid fibril formation, whereas Ins2 B9-23 and the Ins2 C19S mutant show slower fibrillization and a structural rearrangement from globular protofibrils to fibrillar aggregates. These differences in aggregation behaviors also manifest in interactions with (-)epigallocatechin gallate (EGCG), a canonical amyloid inhibitor. EGCG effectively disrupts the fibrils formed by Ins1 B9-23 and the Y16A mutant. However, it proves ineffective in preventing fibril formation of Ins2 B9-23 and the C19S mutant. These results establish a strong correlation between the aggregation behaviors of these peptides and their divergent effects on anti-islet autoimmunity.

Impact of Educational Videos on Patient Understanding of Interventional Radiology Procedures.

RATIONALE AND OBJECTIVES: Under-awareness of Interventional Radiology (IR) care by the public has been reported. The aim of this study is to evaluate the impact of educational videos to facilitate better patient understanding during the informed consent process. MATERIALS AND METHODS: Educational videos for six common IR procedures including chemoembolization, radioembolization, ablation, tunneled central venous catheter placement, port placement, and port removal were developed for educating patients in the pre-procedural setting. One hundred and eighty patients referred to a tertiary academic institution were randomly selected to participate, including 30 patients per procedure type. Anonymous seven question, five-point Likert-scale assessments were administered to the participants before and after engaging with the videos. The survey evaluated patients' perceived understanding of IR procedures and satisfaction with the videos as educational tools. RESULTS: One hundred and eighty patients completed the survey. Comparing post-video to pre-video ratings, there was an increase in patients' understanding of the involved anatomy (4.5 vs 3.3; p < 0.01), understanding of procedure benefits (4.6 vs 3.7; p < 0.01), understanding of procedural risks (4.5 vs 3.3; p < 0.01), understanding of procedural alternatives (3.4 vs 2.7; p < 0.01), and overall procedural understanding (4.7 vs 3.4; p < 0.01). Additionally, patients had a positive impression of the videos with a mean overall satisfaction rating of the video-assisted explanation of 4.80. CONCLUSIONS: A patient-centric video-assisted informed consent for IR procedures enhances patients' understanding and results in high patient satisfaction.

Stepwise developmental mimicry generates proximal-biased kidney organoids.

The kidney maintains body fluid homeostasis by reabsorbing essential compounds and excreting waste. Proximal tubule cells, crucial for renal reabsorption of a range of sugars, ions, and amino acids, are highly susceptible to damage, leading to pathologies necessitating dialysis and kidney transplants. While human pluripotent stem cell-derived kidney organoids are used for modeling renal development, disease, and injury, the formation of proximal nephron cells in these 3D structures is incomplete. Here, we describe how to drive the development of proximal tubule precursors in kidney organoids by following a blueprint of in vivo human nephrogenesis. Transient manipulation of the PI3K signaling pathway activates Notch signaling in the early nephron and drives nephrons toward a proximal precursor state. These "proximal-biased" (PB) organoid nephrons proceed to generate proximal nephron precursor cells. Single-cell transcriptional analyses across the organoid nephron differentiation, comparing control and PB types, confirm the requirement of transient Notch signaling for proximal development. Indicative of functional maturity, PB organoids demonstrate dextran and albumin uptake, akin to in vivo proximal tubules. Moreover, PB organoids are highly sensitive to nephrotoxic agents, display an injury response, and drive expression of HAVCR1 / KIM1 , an early proximal-specific marker of kidney injury. Injured PB organoids show evidence of collapsed tubules, DNA damage, and upregulate the injury-response marker SOX9 . The PB organoid model therefore has functional relevance and potential for modeling mechanisms underpinning nephron injury. These advances improve the use of iPSC-derived kidney organoids as tools to understand developmental nephrology, model disease, test novel therapeutics, and for understanding human renal physiology.

What are the Protocols and Resources for Sport-Related Concussion Among Top National Collegiate Athletic Association Football Programs? A Cross-Sectional Survey of A5 Schools.

OBJECTIVE: This study summarizes findings from a cross-sectional survey conducted among National Collegiate Athletic Association (NCAA) Division 1 football programs, focusing on sport-related concussion (SRC) protocols for the 2018 season. DESIGN: Cross-sectional survey study. SETTING: 65 football programs within the Autonomy Five (A5) NCAA conferences. PARTICIPANTS: Athletic trainers and team physicians who attended a football safety meeting at the NCAA offices June 17 to 18, 2019, representing their respective institutions. INTERVENTION: Electronic surveys were distributed on June 14, 2019, before the football safety meeting. MAIN OUTCOME MEASURES: Results for 16 unique questions involving SRC protocols and resources were summarized and evaluated. RESULTS: The survey garnered responses from 46 of 65 programs (response rate = 71%). For baseline testing, 98% measured baseline postural stability and balance, 87% used baseline neurocognitive testing, while only 61% assessed baseline vestibular and/or ocular function. Regarding concussion prevention, 51% did not recommend additional measures, while 4% and 24% recommended cervical compression collars and omega-3 supplementation, respectively. In postconcussion treatment, 26% initiated aerobic exercise 1 day postconcussion if symptoms were stable, 24% waited at least 48 hours, 4% waited for the athlete to return to baseline, 11% waited until the athlete became asymptomatic, and 35% determined procedures on a case-by-case basis. CONCLUSIONS: Most institutions assessed postural stability/balance and neurocognitive functioning at baseline and introduced light aerobic exercise within 48 h postconcussion. There was variation in baseline assessment methods and concussion prevention recommendations. These survey findings deepen our understanding of diverse SRC protocols in NCAA football programs.

Sport-related concussions in baseball and softball: do mechanisms of injury affect recovery?

OBJECTIVE: Baseball and softball pose unique risks for sport-related concussion (SRC). Although these are not collision sports, concussions in baseball and softball can nonetheless involve high-speed impacts. In a regional, single-institution cohort of baseball and softball athletes who sustained an SRC, the current study sought to 1) describe the mechanisms of injury that led to SRC, and 2) compare initial symptom burden and recovery metrics across mechanisms, including time to return to learn (RTL), time to symptom resolution, and time to return to play (RTP) by mechanism of injury. METHODS: A retrospective cohort study was performed of baseball and softball athletes 12 to 23 years old who sustained an SRC between November 2017 and April 2022. Mechanisms of injury were divided into two categories: 1) contact mechanism (i.e., what initiated contact with the injured player, such as head-to-ball), and 2) player mechanism (i.e., the action the injured player was performing at the time of injury, such as fielding). The recovery outcomes of time to RTL, symptom resolution, and RTP were compared between mechanisms using bivariate analysis and multivariable regression analysis, controlling for sex, age, time to present to concussion clinic, and initial total symptom score. RESULTS: The sample included 58 baseball and softball players (60.3% female, mean age 16.0 ± 1.9 years). Most SRCs (62.1%) occurred during competition. Head-to-ball (50.0%) was the most common contact mechanism, followed by head-to-head/body (31.0%) and head-to-wall/ground/equipment (17.2%). Fielding (63.8%) was the most common player mechanism, followed by drills (20.7%) and running (13.8%). SRCs sustained in practice had significantly longer RTL (median 10.0 [interquartile range (IQR) 3.3-16.3] vs 4.0 [IQR 2.0-8.0] days; U = 421.5, p = 0.031) and symptom resolution (37.0 [IQR 18.0-90.0] vs 14.0 [IQR 7.0-41.0] days; U = 406.5, p = 0.025) compared with SRCs sustained in competition. Multivariable regression analysis revealed that head-to-wall/ground/equipment contact mechanism was associated with longer RTL (ß = 0.30, 95% CI 0.07-0.54, p = 0.013). CONCLUSIONS: The current study found that SRCs in baseball and softball occurred more often in competition than in practice. Head-to-ball and fielding were the most common contact and player mechanisms, respectively. SRCs sustained in practice were associated with longer time to RTL and symptom resolution, and head-to-wall/ground/equipment was associated with longer RTL in multivariable regression analysis. These results provide empirical data to improve concussion safety in baseball/softball.

Solution studies, synthesis and antibacterial activity of Ga(III) complexes with bis-kojate derivatives.

Given the recognized major problem of microbial drug resistance for human health, new metal-based drugs have been currently explored for their antimicrobial properties, including gallium-based compounds as potential metallophores that could perturb Fe's interactions with proteins. Herein we have designed and synthesized two bis-kojate ligands (named L4 and L6) and studied their Ga(III) complexes for their physico-chemical and biological properties. In particular a detailed study of their complexation properties in aqueous solution, showed equilibrium models with formation of quite stable dinuclear 2:3 metal:ligand complexes, though with different stability. Solid state complexes were also prepared and characterized and complementary DFT studies indicated that [Ga2(L4)3] complex, with higher stability, seems to adopt a three-ligand bridging conformation, while that for L6 adopt a one ligand bridging conformation. Preliminary investigation of the antibacterial activity of these gallium complexes showed antipseudomonal activity, which appeared higher for the complex with L4, a feature of potential interest for the scientific community.

Obstacles to receiving postoperative radiation therapy following separation surgery for metastatic spine disease.

OBJECTIVE: Obtaining timely postoperative radiotherapy (RT) following separation surgery is critical to avoid local recurrence of disease yet can be a challenge due to scheduling conflicts, insurance denials, and travel arrangements. In patients undergoing metastatic spine surgery for spinal cord compression, the authors sought to: 1) report the rate of postoperative RT, 2) describe reasons for patients not receiving postoperative RT, and 3) investigate factors that may predict whether a patient receives postoperative RT. METHODS: A single-center retrospective case series was undertaken of all patients who underwent metastatic spine surgery for extradural disease between January 2010 and January 2021. Inclusion criteria were patients with intermediate or radioresistant tumors with evidence of spinal cord compression who underwent surgery. The primary outcome was the occurrence of RT within 3 months following surgery. Multivariable logistic regression analysis was performed controlling for age, BMI, race, total number of decompressed levels, tumor size, other organ metastasis, and preoperative RT or chemotherapy to predict patients receiving postoperative RT. RESULTS: Of 239 patients undergoing spine surgery for metastatic disease, 113 (47.3%) received postoperative RT while 126 (52.7%) did not. In the postoperative RT group, 24 (21.2%) received stereotactic body radiation therapy while 89 (78.8%) received conventional external-beam radiation therapy. The most common reasons for patients not receiving postoperative RT included death or transfer to hospice (31.0%), RT not being recommended by radiation oncology (30.2%), and loss to follow-up (23.8%). On critical review with the radiation oncology department, the authors estimated that 101 of 126 (80.2%) patients who did not receive postoperative RT were potential candidates for postoperative RT. Patients who received postoperative RT had more documented inpatient (48.7% vs 32.5%, p < 0.001) and outpatient (100.0% vs 65.1%, p < 0.001) radiation oncology consultations than those who did not. Additionally, patients who received postoperative RT had a higher rate of postoperative chemotherapy (53.1% vs 25.4%, p < 0.001), while patients who did not receive postoperative RT had a higher rate of preoperative RT (7.1% vs 31.0%, p < 0.001). Multivariable analysis confirmed that patients who received preoperative RT had lower odds of undergoing postoperative RT (OR 0.14, 95% CI 0.06-0.34; p < 0.001), and patients who underwent postoperative chemotherapy had higher odds of undergoing postoperative RT (OR 3.83, 95% CI 2.05-7.17; p < 0.001). CONCLUSIONS: In the current study reflecting real-world care of patients with metastatic spine disease after undergoing separation surgery, 47% of patients did not receive postoperative RT, and 80% of those patients were potential candidates for postoperative RT. Radiation oncology consultation and postoperative chemotherapy were significantly associated with receiving postoperative RT, whereas preoperative RT was significantly associated with not receiving postoperative RT. The lack of timely postoperative RT highlights a potential gap in metastatic spine tumor care and underscores the necessity for prompt radiation oncology consultation and effective planning.

The current landscape of machine learning-based radiomics in arteriovenous malformations: a systematic review and radiomics quality score assessment.

Background: Arteriovenous malformations (AVMs) are rare vascular anomalies involving a disorganization of arteries and veins with no intervening capillaries. In the past 10 years, radiomics and machine learning (ML) models became increasingly popular for analyzing diagnostic medical images. The goal of this review was to provide a comprehensive summary of current radiomic models being employed for the diagnostic, therapeutic, prognostic, and predictive outcomes in AVM management. Methods: A systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, in which the PubMed and Embase databases were searched using the following terms: (cerebral OR brain OR intracranial OR central nervous system OR spine OR spinal) AND (AVM OR arteriovenous malformation OR arteriovenous malformations) AND (radiomics OR radiogenomics OR machine learning OR artificial intelligence OR deep learning OR computer-aided detection OR computer-aided prediction OR computer-aided treatment decision). A radiomics quality score (RQS) was calculated for all included studies. Results: Thirteen studies were included, which were all retrospective in nature. Three studies (23%) dealt with AVM diagnosis and grading, 1 study (8%) gauged treatment response, 8 (62%) predicted outcomes, and the last one (8%) addressed prognosis. No radiomics model had undergone external validation. The mean RQS was 15.92 (range: 10-18). Conclusion: We demonstrated that radiomics is currently being studied in different facets of AVM management. While not ready for clinical use, radiomics is a rapidly emerging field expected to play a significant future role in medical imaging. More prospective studies are warranted to determine the role of radiomics in the diagnosis, prediction of comorbidities, and treatment selection in AVM management.

Stopping at C2 Versus C3/4 in Elective Posterior Cervical Decompression and Fusion: A 5-Year Follow-up Study.

STUDY DESIGN: This is a retrospective cohort study. OBJECTIVE: In patients undergoing elective posterior cervical laminectomy and fusion (PCLF) with a minimum of 5-year follow-up, we sought to compare reoperation rates between patients with an upper instrumented vertebra (UIV) of C2 versus C3/4. SUMMARY OF BACKGROUND DATA: The long-term outcomes of choosing between C2 versus C3/4 as the UIV in PCLF remain unclear. METHODS: A single-institution, retrospective cohort study from a prospective registry was conducted of patients undergoing elective, degenerative PCLF from December 2010 to June 2018. The primary exposure was UIV of C2 versus C3/4. The primary outcome was reoperation. Multivariable logistic regression controlled for age, smoking, diabetes, and fusion to the thoracic spine. RESULTS: Of the 68 patients who underwent PCLF with 5-year follow-up, 27(39.7%) had a UIV of C2, and 41(60.3%) had a UIV of either C3/4. Groups had similar duration of symptoms (P=0.743), comorbidities (P>0.999), and rates of instrumentation to the thoracic spine (70.4% vs. 53.7%, P=0.210). The C2 group had significantly longer operative time (231.8±65.9 vs. 181.6±44.1 mins, P<0.001) and more fused segments (5.9±1.8 vs. 4.2±0.9, P<0.001). Reoperation rate was lower in the C2 group compared with C3/4 (7.4% vs. 19.5%), though this did not reach statistical significance (P=0.294). Multivariable logistic regression showed increased odds of reoperation for the C3/4 group compared with the C2 group (OR=3.29, 95%CI=0.59-18.11, P=0.170), though statistical significance was not reached. Similarly, the C2 group had a lower rate of instrumentation failure (7.4% vs. 12.2%, P=0.694) and adjacent segment disease/disk herniation (0% vs. 7.3%, P=0.271), though neither trend attained statistical significance. CONCLUSIONS: Patients with a UIV of C2 had less than half the number of reoperations and less adjacent segment disease, though neither trend was statistically significant. Despite a lack of statistical significance, whether a clinically meaningful difference exists between UIV of C2 versus C3/4 should be validated in larger samples with long-term follow-up. LEVEL OF EVIDENCE: Level-3.

Long-term expandable mouse and human-induced nephron progenitor cells enable kidney organoid maturation and modeling of plasticity and disease.

Nephron progenitor cells (NPCs) self-renew and differentiate into nephrons, the functional units of the kidney. Here, manipulation of p38 and YAP activity allowed for long-term clonal expansion of primary mouse and human NPCs and induced NPCs (iNPCs) from human pluripotent stem cells (hPSCs). Molecular analyses demonstrated that cultured iNPCs closely resemble primary human NPCs. iNPCs generated nephron organoids with minimal off-target cell types and enhanced maturation of podocytes relative to published human kidney organoid protocols. Surprisingly, the NPC culture medium uncovered plasticity in human podocyte programs, enabling podocyte reprogramming to an NPC-like state. Scalability and ease of genome editing facilitated genome-wide CRISPR screening in NPC culture, uncovering genes associated with kidney development and disease. Further, NPC-directed modeling of autosomal-dominant polycystic kidney disease (ADPKD) identified a small-molecule inhibitor of cystogenesis. These findings highlight a broad application for the reported iNPC platform in the study of kidney development, disease, plasticity, and regeneration.

Post-Transcriptional Modular Synthetic Receptors.

Inspired by the power of transcriptional synthetic receptors and hoping to complement them to expand the toolbox for cell engineering, we establish LIDAR (Ligand-Induced Dimerization Activating RNA editing), a modular post-transcriptional synthetic receptor platform that harnesses RNA editing by ADAR. LIDAR is compatible with various receptor architectures in different cellular contexts, and enables the sensing of diverse ligands and the production of functional outputs. Furthermore, LIDAR can sense orthogonal signals in the same cell and produce synthetic spatial patterns, potentially enabling the programming of complex multicellular behaviors. Finally, LIDAR is compatible with compact encoding and can be delivered by synthetic mRNA. Thus, LIDAR expands the family of synthetic receptors, holding the promise to empower basic research and therapeutic applications.

The Lunar Environment Heliophysics X-ray Imager (LEXI) Mission.

The Lunar Environment heliospheric X-ray Imager (LEXI) is a wide field-of-view soft X-ray telescope developed to study solar wind-magnetosphere coupling. LEXI is part of the Blue Ghost 1 mission comprised of 10 payloads to be deployed on the lunar surface. LEXI monitors the dayside magnetopause position and shape as a function of time by observing soft X-rays (0.1-2 keV) emitted from solar wind charge-exchange between exospheric neutrals and high charge-state solar wind plasma in the dayside magnetosheath. Measurements of the shape and position of the magnetopause are used to test temporal models of meso- and macro-scale magnetic reconnection. To image the boundary, LEXI employs lobster-eye optics to focus X-rays to a microchannel plate detector with a 9.1×∘9.1∘ field of view.

Low serum creatinine levels are associated with major post-operative complications in patients undergoing surgery with gynecologic oncologists.

OBJECTIVE: Serum creatinine is a byproduct of muscle metabolism, and low creatinine is postulated to be associated with diminished muscle mass. This study examined the association between low pre-operative serum creatinine and post-operative outcomes. METHODS: This retrospective cohort study utilized the 2014-2021 National Surgical Quality Improvement Program to identify patients undergoing surgery with gynecologic oncologists. Patients with missing pre-operative creatinine, end-stage renal disease, sepsis, septic shock, dialysis, or pregnancy were excluded. Pre-operative creatinine was categorized into markedly low (≤0.44 mg/dL), mildly low (0.45-0.64 mg/dL), normal (0.65-0.84 mg/dL), and four categories of elevated levels (0.85-1.04, 1.05-1.24, 1.25-1.44, and ≥1.45 mg/dL). Outcomes included major (≥Grade 3) 30-day complications, categorized into any complications, wound, cardiovascular and pulmonary, renal, infectious, and thromboembolic complications. Also examined were 30-day readmissions, reoperations, and mortality. Logistic regressions assessed the association between creatinine and complications, with stratification by albumin and sensitivity analysis with propensity score matching. RESULTS: Among 84 786 patients, 0.8% had markedly low, 19.6% mildly low, and 50.2% normal creatinine; the remainder had elevated creatinine. As creatinine decreased, the risks of major complications increased in a dose-dependent manner on univariable and multivariable analyses. A total of 9.6% (n=63) markedly low patients experienced major complications, second to creatinine ≥1.45 mg/dL (9.9%, n=141). On multivariable models, both markedly and mildly low creatinine were associated with higher odds of major complications (OR 1.715, 95% CI 1.299 to 2.264 and OR 1.093, 95% CI 1.001 to 1.193) and infections (OR 1.575, 95% CI 1.118 to 2.218 and OR 1.165, 95% CI 1.048 to 1.296) versus normal. Markedly low creatinine had similar ORs to creatinine ≥1.45 mg/dL and was further associated with higher odds of cardiovascular and pulmonary complications (OR 2.301, 95% CI 1.300 to 4.071), readmissions (OR 1.403, 95% CI 1.045 to 1.884), and mortality (OR 2.718, 95% CI 1.050 to 7.031). After albumin stratification, associations persisted for markedly low creatinine. Propensity-weighted analyses demonstrated congruent findings. CONCLUSIONS: Low creatinine levels are associated with major post-operative complications in gynecologic oncology in a dose-dependent manner. Low creatinine can offer useful information for pre-operative risk stratification, surgical counseling, and peri-operative management.

Retinoids in the treatment of photoageing: A histological study of topical retinoid efficacy in black skin.

BACKGROUND: Photoageing describes complex cutaneous changes that occur due to chronic exposure to solar ultraviolet radiation (UVR). The 'gold standard' for the treatment of photoaged white skin is all-trans retinoic acid (ATRA); however, cosmetic retinol (ROL) has also proven efficacious. Recent work has identified that black skin is susceptible to photoageing, characterized by disintegration of fibrillin-rich microfibrils (FRMs) at the dermal-epidermal junction (DEJ). However, the impact of topical retinoids for repair of black skin has not been well investigated. OBJECTIVES: To determine the potential of retinoids to repair photoaged black skin. METHODS: An exploratory intervention study was performed using an in vivo, short-term patch test protocol. Healthy but photoaged black volunteers (>45 years) were recruited to the study, and participant extensor forearms were occluded with either 0.025% ATRA (n = 6; 4-day application due to irritancy) or ROL (12-day treatment protocol for a cosmetic) at concentrations of 0.3% (n = 6) or 1% (n = 6). Punch biopsies from occluded but untreated control sites and retinoid-treated sites were processed for histological analyses of epidermal characteristics, melanin distribution and dermal remodelling. RESULTS: Treatment with ATRA and ROL induced significant acanthosis (all p < 0.001) accompanied by a significant increase in keratinocyte proliferation (Ki67; all p < 0.01), dispersal of epidermal melanin and restoration of the FRMs at the DEJ (all p < 0.01), compared to untreated control. CONCLUSIONS: This study confirms that topical ATRA has utility for the repair of photoaged black skin and that ROL induces comparable effects on epidermal and dermal remodelling, albeit over a longer timeframe. The effects of topical retinoids on black photoaged skin are similar to those reported for white photoaged skin and suggest conserved biology in relation to repair of UVR-induced damage. Further investigation of topical retinoid efficacy in daily use is warranted for black skin.

The activity advantage: Objective measurement of preoperative activity is associated with postoperative recovery and outcomes in patients undergoing surgery with gynecologic oncologists.

OBJECTIVE: To examine the association between objectively-measured preoperative physical activity with postoperative outcomes and recovery milestones in patients undergoing gynecologic oncology surgeries. METHODS: Prospective cohort study of patients undergoing surgery with gynecologic oncologists who wore wearable actigraphy rings before and after surgery from 03/2021-11/2023. Exposures encompassed preoperative activity intensity (moderate- and vigorous-intensity metabolic equivalent of task-minutes [MAVI MET-mins] over seven days) and level (average daily steps over seven days). Intensity was categorized as <500, 500-1000, and >1000 MAVI MET-mins; level categorized as <8000 and ≥8000 steps/day. Primary outcome was 30-day complications. Secondary outcomes included reaching postoperative goal (≥70% of recommended preoperative intensity and level thresholds) and return to baseline (≥70% of individual preoperative intensity and level). RESULTS: Among 96 enrolled, 87 met inclusion criteria, which constituted 39% (n = 34) with <500 MET-mins and 56.3% (n = 49) with <8000 steps preoperatively. Those with <500 MET-mins and <8000 steps had higher ECOG scores (p = 0.042 & 0.037) and BMI (p = 0.049 & 0.002) vs those with higher activity; all other perioperative characteristics were similar between groups. Overall, 29.9% experienced a 30-day complication, 29.9% reached postoperative goal, and 64.4% returned to baseline. On multivariable models, higher activity was associated with lower odds of complications: 500-1000 MET-mins (OR = 0.26,95%CI = 0.07-0.92) and >1000 MET-mins (OR = 0.25,95%CI = 0.07-0.94) vs <500 MET-mins; ≥8000 steps (OR = 0.25,95%CI = 0.08-0.73) vs <8000 steps. Higher preoperative activity was associated fewer days to reach postoperative goal. CONCLUSION: Patients with high preoperative activity are associated with fewer postoperative complications and faster attainment of recovery milestones. Physical activity may be considered a modifiable risk factor for adverse postoperative outcomes.

Rapamycin does not alter bone microarchitecture or material properties quality in young-adult and aged female C57BL/6 mice.

Advancing age is the strongest risk factor for osteoporosis and skeletal fragility. Rapamycin is an FDA-approved immunosuppressant that inhibits the mechanistic target of rapamycin (mTOR) complex, extends lifespan, and protects against aging-related diseases in multiple species; however, the impact of rapamycin on skeletal tissue is incompletely understood. We evaluated the effects of a short-term, low-dosage, interval rapamycin treatment on bone microarchitecture and strength in young-adult (3 mo old) and aged female (20 mo old) C57BL/6 mice. Rapamycin (2 mg/kg body mass) was administered via intraperitoneal injection 1×/5 d for a duration of 8 wk; this treatment regimen has been shown to induce geroprotective effects while minimizing the side effects associated with higher rapamycin dosages and/or more frequent or prolonged delivery schedules. Aged femurs exhibited lower cancellous bone mineral density, volume, trabecular connectivity density and number, higher trabecular thickness and spacing, and lower cortical thickness compared to young-adult mice. Rapamycin had no impact on assessed microCT parameters. Flexural testing of the femur revealed that both yield strength and ultimate strength were lower in aged mice compared to young-adult mice. There were no effects of rapamycin on these or other measures of bone biomechanics. Age, but not rapamycin, altered local and global measures of bone turnover. These data demonstrate that short-term, low-dosage interval rapamycin treatment does not negatively or positively impact the skeleton of young-adult and aged mice.

Is ChatGPT a trusted source of information for total hip and knee arthroplasty patients?

Aims: While internet search engines have been the primary information source for patients' questions, artificial intelligence large language models like ChatGPT are trending towards becoming the new primary source. The purpose of this study was to determine if ChatGPT can answer patient questions about total hip (THA) and knee arthroplasty (TKA) with consistent accuracy, comprehensiveness, and easy readability. Methods: We posed the 20 most Google-searched questions about THA and TKA, plus ten additional postoperative questions, to ChatGPT. Each question was asked twice to evaluate for consistency in quality. Following each response, we responded with, "Please explain so it is easier to understand," to evaluate ChatGPT's ability to reduce response reading grade level, measured as Flesch-Kincaid Grade Level (FKGL). Five resident physicians rated the 120 responses on 1 to 5 accuracy and comprehensiveness scales. Additionally, they answered a "yes" or "no" question regarding acceptability. Mean scores were calculated for each question, and responses were deemed acceptable if ≥ four raters answered "yes." Results: The mean accuracy and comprehensiveness scores were 4.26 (95% confidence interval (CI) 4.19 to 4.33) and 3.79 (95% CI 3.69 to 3.89), respectively. Out of all the responses, 59.2% (71/120; 95% CI 50.0% to 67.7%) were acceptable. ChatGPT was consistent when asked the same question twice, giving no significant difference in accuracy (t = 0.821; p = 0.415), comprehensiveness (t = 1.387; p = 0.171), acceptability (χ2 = 1.832; p = 0.176), and FKGL (t = 0.264; p = 0.793). There was a significantly lower FKGL (t = 2.204; p = 0.029) for easier responses (11.14; 95% CI 10.57 to 11.71) than original responses (12.15; 95% CI 11.45 to 12.85). Conclusion: ChatGPT answered THA and TKA patient questions with accuracy comparable to previous reports of websites, with adequate comprehensiveness, but with limited acceptability as the sole information source. ChatGPT has potential for answering patient questions about THA and TKA, but needs improvement.

Shifting trends and sicker patients: Reassessing hysterectomy performed for benign indications by gynecologic oncologists.

OBJECTIVE: To assess trends and differences in patient characteristics, complications, and distributions of hysterectomy for benign indications by benign gynecologists (BG) and gynecologic oncologists (GO). METHODS: This retrospective cohort study identified patients undergoing hysterectomy for benign indications using the National Surgical Quality Improvement Program data from 2014 to 2021. Exclusions were made for gynecologic or disseminated cancers, ascites, non-gynecologic surgeons, and cesarean hysterectomies. Primary outcome was major (≥Grade 3) 30-day complications, categorized into any complications, wound, cardiovascular and pulmonary, renal, infectious, andthromboembolic complications. Thirty-day readmissions, reoperations, and mortality were also analyzed. Propensity score matching was performed in a 1:1 match of GO to BG patients and was compared. Linear regressions assessed trends. RESULTS: Among 198,767 patients, 18% (n = 37,707) underwent hysterectomy for benign indications with GO. GO patients exhibited more risk factors for complications and differed significantly from BG patients in comorbidities and perioperative characteristics. Overall, GO patients had higher major complication rates (3.1% vs 2.2%, p < 0.001) and for several other composite complications. After matching, compared to BG, GO-performed hysterectomies had similar rates of major complications (3.0% vs 3.0%, p = 0.55) and no differences in other composite complications, except fewer reoperations (1.2 % vs 1.5%, p < 0.01) and wound complications (0.4% vs 0.5%, p = 0.02) in GO patients. Over the eight years, the percentage of GO-performed hysterectomy (ß = 0.41, R2 = 0.71,p < 0.01) increased significantly whereas BG-performed surgeries decreased by the same magnitude. BG had a significant decrease in frail patients (ß = -0.47, R2 = 0.90, p < 0.01), but GO did not (ß = -0.36, R2 = 0.38, p = 0.10). CONCLUSIONS: GO are performing more hysterectomies for benign indications on higher-risk patients. However, on a matched cohort, risks of major complications were similar between GO and BG.

In the patient's shoes: The impact of hospital proximity and volume on stage I endometrial cancer care patterns and outcomes.

OBJECTIVE: To compare the impact of travel burden and hospital volume on care patterns and outcomes in stage I endometrial cancer. METHODS: This retrospective cohort study identified patients from the National Cancer Database with stage I epithelial endometrial carcinoma who underwent hysterectomy between 2012 and 2020. Patients were categorized into: lowest quartiles of travel distance and hospital surgical volume for endometrial cancer (Local) and highest quartiles of distance and volume (Travel). Primary outcome was overall survival. Secondary outcomes were surgery route, lymph node (LN) assessment method, length of stay (LOS), 30-day readmission, and 30- and 90-day mortality. Results were stratified by tumor recurrence risk. Outcomes were compared using propensity-score matching. Propensity-adjusted survival was evaluated using Kaplan-Meier curves and compared using log-rank tests. Cox models estimated hazard ratios for death. Sensitivity analysis using modified Poisson regressions was performed. RESULTS: Among 36,514 patients, 51.4% were Local and 48.6% Travel. The two cohorts differed significantly in demographics and clinicopathologic characteristics. Upon propensity-score matching (p < 0.05 for all), more Travel patients underwent minimally invasive surgery (88.1%vs79.1%) with fewer conversions to laparotomy (2.0%vs2.6%), more sentinel (20.5%vs11.3%) and fewer traditional LN assessments (58.1vs61.7%) versus Local. Travel patients had longer intervals to surgery (≥30 days:56.7%vs50.1%) but shorter LOS (<2 days:76.9%vs59.8%), fewer readmissions (1.9%vs2.7%%), and comparable 30- and 90-day mortality. OS and HR for death remained comparable between the matched groups. CONCLUSIONS: Compared to surgery in nearby low-volume hospitals, patients with stage I epithelial endometrial cancer who travelled longer distances to high-volume centers experienced more favorable short-term outcomes and care patterns with comparable long-term survival.

Conservative Management of LVAD-Associated Ventricular Pseudoaneurysm.

Left ventricular assist devices (LVAD) are surgically implanted mechanical support devices utilized with increasing frequency as a bridge to myocardial recovery, destination therapy, and heart transplantation. While the use of such devices in patients with advanced heart failure has shown significant survival benefits and improved quality of life, they bear their own risks and complications.1 Bleeding, infection, pump thrombosis, and stroke are just some of the serious complications associated with LVADs.2 LVAD-associated pseudoaneurysms are rare, with prior reports of occurrence at the left ventricular apex and at the anastomosis site of the outflow graft to the ascending aorta.3,4 Typically, this device-related complication requires surgical repair and, if at all feasible, heart transplantation. However, in cases of difficult anatomy, unfavorable position, and significant comorbidities, surgery may be contraindicated due to high surgical risk. This case portrays a patient suffering from a left ventricular pseudoaneurysm after HeartMate-III implantation that was not amenable to surgical repair due to heightened surgical risk. We document the first pseudoaneurysm associated with the HeartMate-III in available literature and describe a novel management strategy of documented nonoperative course of LVAD-associated pseudoaneurysm, with the patient surviving 56+ months with medical optimization and management.