Fully automated determination of robotic pedicle screw accuracy and precision utilizing computer vision algorithms.

Historically, pedicle screw accuracy measurements have relied on CT and expert visual assessment of the position of pedicle screws relative to preoperative plans. Proper pedicle screw placement is necessary to avoid complications, cost and morbidity of revision procedures. The aim of this study was to determine accuracy and precision of pedicle screw insertion via a novel computer vision algorithm using preoperative and postoperative computed tomography (CT) scans. Three cadaveric specimens were utilized. Screw placement planning on preoperative CT was performed according to standard clinical practice. Two experienced surgeons performed bilateral T2-L4 instrumentation using robotic-assisted navigation. Postoperative CT scans of the instrumented levels were obtained. Automated segmentation and computer vision techniques were employed to align each preoperative vertebra with its postoperative counterpart and then compare screw positions along all three axes. Registration accuracy was assessed by preoperatively embedding spherical markers (tantalum beads) to measure discrepancies in landmark alignment. Eighty-eight pedicle screws were placed in 3 cadavers' spines. Automated registrations between pre- and postoperative CT achieved sub-voxel accuracy. For the screw tip and tail, the mean three-dimensional errors were 1.67 mm and 1.78 mm, respectively. Mean angular deviation of screw axes from plan was 1.58°. For screw mid-pedicular accuracy, mean absolute error in the medial-lateral and superior-inferior directions were 0.75 mm and 0.60 mm, respectively. This study introduces automated algorithms for determining accuracy and precision of planned pedicle screws. Our accuracy outcomes are comparable or superior to recent robotic-assisted in vivo and cadaver studies. This computerized workflow establishes a standardized protocol for assessing pedicle screw placement accuracy and precision and provides detailed 3D translational and angular accuracy and precision for baseline comparison.

The Role of Aging and Senescence in Immune Checkpoint Inhibitor Response and Toxicity.

Cellular senescence accumulates with age and has been shown to impact numerous physiological and pathological processes, including immune function. The role of cellular senescence in cancer is multifaceted, but the impact on immune checkpoint inhibitor response and toxicity has not been fully evaluated. In this review, we evaluate the impact of cellular senescence in various biological compartments, including the tumor, the tumor microenvironment, and the immune system, on immune checkpoint inhibitor efficacy and toxicity. We provide an overview of the impact of cellular senescence in normal and pathological contexts and examine recent studies that have connected aging and cellular senescence to immune checkpoint inhibitor treatment in both the pre-clinical and clinical contexts. Overall, senescence plays a multi-faceted, context-specific role and has been shown to modulate immune-related adverse event incidence as well as immune checkpoint inhibitor response.

Injuries With Electric vs Conventional Scooters and Bicycles.

Importance: Micromobility, the use of small vehicles (primarily scooters and bicycles), has become a standard transportation method in the US. Despite broad adoption of electric micromobility vehicles, there is a paucity of data regarding the injury profiles of these vehicles, particularly in the US. Objective: To characterize micromobility injury trends in the US, identify demographic characteristic differences in users of electric and conventional vehicles, and identify factors associated with hospitalization. Design, Setting, and Participants: This cross-sectional study queried the National Electronic Injury Surveillance System, a comprehensive database that collates injury data associated with consumer products from emergency departments across the US to provide national estimates, from calendar year 2017 to 2022. Data on micromobility vehicle injuries (bicycles, scooters, electric bicycles [e-bicycles], and electric scooters [e-scooters]) were obtained. Main Outcomes and Measures: Trends in injury and hospitalization counts, injury characteristics, and factors associated with hospitalization. Results: From 2017 to 2022, the US recorded 2 499 843 bicycle (95% CI, 1 948 539-3 051 147), 304 783 scooter (95% CI, 232 466-377 099), 45 586 e-bicycle (95% CI, 17 684-73 488), and 189 517 e-scooter (95% CI, 126 101-252 932) injuries. The median age of the riders was 28 (IQR, 12-51) years; 72% were male, 1.5% Asian, 13% Black, 12% Hispanic, and 49% White. Annual e-bicycle and e-scooter injuries increased from 751 (95% CI, 0-1586) to 23 493 (95% CI, 11 043-35 944) and injuries increased from 8566 (95% CI, 5522-11 611) to 56 847 (95% CI, 39 673-74 022). Compared with conventional vehicles, electric vehicle accidents involved older individuals (median age, 31 vs 27 years; P < .001) and a higher proportion of Black riders (25% vs 12%; P < .001). Helmet use was less in electric vehicle incidents compared with conventional vehicles (43% vs 52%; P = .02), and injuries were more common in urban settings (83% vs 71%; P = .008). Age-adjusted odds of hospitalization among all Black individuals compared with White individuals was 0.76 (95% CI, 0.59-0.98; P = .04). Conclusions and Relevance: In this cross-sectional study of micromobility vehicles, an increased number of injuries and hospitalizations was observed with electric vehicles compared with conventional vehicles from 2017 to 2022. These findings suggest the need for change in educational policies, infrastructure, and law to recenter on safety with the use of micromobility vehicles.

Measuring and Understanding Market Exclusivity Length for New Prescription Drugs in France, Australia, and the USA.

BACKGROUND: Originator drug manufacturers use several strategies to delay generic competition in the USA, but it remains unclear whether this results in longer market exclusivity compared to other countries. OBJECTIVES: We sought to understand how drug market exclusivity lengths vary between the USA and two comparable countries. METHODS: We focused on drugs approved within 2 years of each other in the USA, France, and Australia from 1995 to 2005, and we compared the lengths of exclusivity from marketing approval through first generic competition or June 2023 using Kaplan-Meier analyses. RESULTS: Among 165 drugs in common between the USA and France, the median length of exclusivity was slightly longer in France (15.0 years, interquartile range [IQR]: 13.0-19.6) than the USA (14.5 years, IQR: 11.7-17.6). Among 100 drugs in common between the USA and Australia, the median length of exclusivity was longer in Australia (16.3 years, IQR: 13.9-22.4) than in the USA (14.4 years, IQR: 12.0-17.1). CONCLUSIONS: Market exclusivity lengths in the USA are not longer than in France and Australia. Potential reasons include the larger US market and incentives that offer transient high generic drug prices in the USA for manufacturers that successfully challenge originator market exclusivity.

The prevalence of sexual grooming behaviors among survivors of childhood sexual abuse.

BACKGROUND: Childhood sexual abuse (CSA) is a global problem that is preventable. Sexual grooming behaviors have been deemed an integral part of CSA for the purpose of avoiding detection and preventing disclosure. Many of these behaviors are reported more often by adults who experienced CSA as compared to those that did not (Jeglic et al., 2023). Such behaviors form important targets for prevention efforts, as well as the investigation and prosecution of CSA. Consequently, it is important to identify the prevalence rates of sexual grooming behaviors. OBJECTIVE: The aim of the present study was to identify the prevalence of sexual grooming as reported by adult survivors of CSA. PARTICIPANTS AND SETTING: A large sample of adults who reported a history of CSA (n = 1045) completed the study online via Prolific. METHODS: Participants completed an anonymous self-report survey which included the Sexual Grooming Scale - Victim Version (Winters & Jeglic, 2022). RESULTS: Overall, 99% of participants endorsed experiencing at least one sexual grooming behavior, with an average of 14.25 sexual grooming behaviors out of a possible 42 (range = 0-36) reported per survivor. Participants endorsed behaviors across all five stages of the sexual grooming process: victim selection, gaining access and isolation, trust development, desensitization, and post-abuse maintenance. The most frequently reported sexual grooming behaviors included the perpetrator selecting a child who was compliant/trusting (68%) or had low self-esteem (61%); arranging activities alone with the child (57%); presenting themselves as nice/charming/likeable (70%); showing the child large amounts of attention (56%) or affection (54%); and using seemingly innocent touch (51%). CONCLUSIONS: Sexual grooming is prevalent based on reports from adult survivors of CSA. These findings will be discussed as they pertain to the prevention, detection, and prosecution of CSA.

State Spending Targets for Prescription Drugs.

This Viewpoint discusses the limitations of state prescription drug spending targets for lowering medication costs.

Updates to Incontinence After Prostate Treatment: AUA/GURS/SUFU Guideline (2024).

PURPOSE: In 2023 the American Urological Association (AUA) requested an Update Literature Review (ULR) to incorporate new evidence generated since the 2019 publication of this Guideline. The resulting 2024 Guideline Amendment addresses updated recommendations to provide guidance for the care of patients with incontinence after prostate treatment (IPT). MATERIALS AND METHODS: In 2023, the IPT Guideline was updated through the AUA amendment process in which newly published literature is reviewed and integrated into previously published guidelines. There were 82 studies of interest initially identified in preliminary abstract review. Following full-text review, 17 studies met inclusion criteria and ultimately informed the statements of interest. RESULTS: The Panel developed evidence- and consensus-based statements based on an updated review to provide guidance for the care of patients who experience IPT. These updates are detailed herein. CONCLUSIONS: As prostate treatments are refined, a decreasing incidence of incontinence is anticipated. This Guideline will require further review as the diagnostic and treatment options for patients with IPT continue to evolve.

Risk Factors for Quantity of Cannabis Use Per Day among College Students Who Violated Their University Drug Use Policy.

Background: Cannabis use among college students represents a continued public health issue. The objective was to assess risk factors and reasons for cannabis use among students who violated their university's drug use policy, and whether risk factors influenced cannabis use quantity. Methods: This cross-sectional survey study included 99 college students enrolled at a large U.S. public university. Descriptive statistics were calculated, and an ordinary least squares regression analysis was conducted. Results: Students reported using cannabis an average of 7.4 (SD = 10.2) days in the past month, with 8% reporting daily use. On average, students consumed slightly over 0.25 (SD = 0.25) grams per day, with 40% reporting greater than one gram per day. The average age of onset of cannabis use was 16.8 (SD = 1.8) years old. The top reasons for cannabis use were to: relax or relieve tension (75.8%), feel good or get high (62.6%), and have a good time with friends (60.6%). Students perceived an average of 47% of their peers engaged in past-month cannabis use and only slight risk was associated with regular use. Students perceived their loved ones would mostly approve of a reduction in their cannabis use. Regression results indicated past-month cannabis frequency (p = .002) and being of racial/ethnic minority descent (p = .05) were positively associated with quantity of cannabis per day, while perceived risk of regular cannabis use (ß = -0.21) was negatively associated. Conclusion: Evidence-based cannabis interventions for students who violate their university's drug use policies are critically needed that aim to reduce cannabis use and mitigate its associated negative consequences.

Artificial neural networks for ECG interpretation in acute coronary syndrome: A scoping review.

INTRODUCTION: The electrocardiogram (ECG) is a crucial diagnostic tool in the Emergency Department (ED) for assessing patients with Acute Coronary Syndrome (ACS). Despite its widespread use, the ECG has limitations, including low sensitivity of the STEMI criteria to detect Acute Coronary Occlusion (ACO) and poor inter-rater reliability. Emerging ECG features beyond the traditional STEMI criteria show promise in improving early ACO diagnosis, but complexity hinders widespread adoption. The potential integration of Artificial Neural Networks (ANN) holds promise for enhancing diagnostic accuracy and addressing reliability issues in ECG interpretation for ACO symptoms. METHODS: Ovid MEDLINE, CINAHL, EMBASE, Cochrane, PubMed and Scopus were searched from inception through to 8th of December 2023. A thorough search of the grey literature and reference lists of relevant articles was also performed to identify additional studies. Articles were included if they reported the use of ANN for ECG interpretation of Acute Coronary Syndrome in the Emergency Department patients. RESULTS: The search yielded a total of 244 articles. After removing duplicates and excluding non-relevant articles, 14 remained for analysis. There was significant heterogeneity in the types of ANN models used and the outcomes assessed, making direct comparisons challenging. Nevertheless, ANN appeared to demonstrate higher accuracy than physician interpreters for the evaluated outcomes and this proved independent of both specialty and years of experience. CONCLUSIONS: The interpretation of ECGs in patients with suspected ACS using ANN appears to be accurate and potentially superior when compared to human interpreters and computerised algorithms. This appears consistent across various ANN models and outcome variables. Future investigations should emphasise ANN interpretation of ECGs in patients with ACO, where rapid and accurate diagnosis can significantly benefit patients through timely access to reperfusion therapies.

Sensitivity of air quality to vehicle ammonia emissions in the United States.

The US Environmental Protection Agency (EPA) estimates on-road vehicles emissions using the Motor Vehicle Emission Simulator (MOVES). We developed updated ammonia emission rates for MOVES based on road-side exhaust emission measurements of light-duty gasoline and heavy-duty diesel vehicles. The resulting nationwide on-road vehicle ammonia emissions are 1.8, 2.1, 1.8, and 1.6 times higher than the MOVES3 estimates for calendar years 2010, 2017, 2024, and 2035, respectively, primarily due to an increase in light-duty gasoline vehicle NH3 emission rates. We conducted an air quality simulation using the Community Multi-Scale Air Quality (CMAQv5.3.2) model to evaluate the sensitivity of modeled ammonia and fine particulate matter (PM2.5) concentrations in calendar year 2017 using the updated on-road vehicle ammonia emissions. The average monthly urban ammonia ambient concentrations increased by up to 2.3 ppbv in January and 3.0 ppbv in July. The updated on-road NH3 emission rates resulted in better agreement of modeled ammonia concentrations with 2017 annual average ambient ammonia measurements, reducing model bias by 5.8 % in the Northeast region. Modeled average winter PM2.5 concentrations increased in urban areas, including enhancements of up to 0.5 µg/m3 in the northeast United States. The updated ammonia emission rates have been incorporated in MOVES4 and will be used in future versions of the NEI and EPA's modeling platforms.

Down Syndrome and Autoimmune Disease.

Down syndrome is the most common genetic cause of intellectual disability and has previously been associated with a variety of autoimmune disorders affecting multiple organ systems. The high prevalence of autoimmune disease, in conjunction with other inflammatory and infectious diseases, in this population suggests an intrinsic immune dysregulation associated with triplication of chromosome 21. Emerging data on the role of chromosome 21 in interferon activation, cytokine production, and activation of B-cell mediated autoimmunity are emerging hypotheses that may explain the elevated prevalence of autoimmune thyroid disease, celiac disease, type I diabetes, autoimmune skin disease, and a variety of autoimmune neurologic conditions. As the life expectancy for individuals with Down syndrome increases, knowledge of the epidemiology, clinical features, management and underlying causes of these conditions will become increasingly important. Disorders such as Hashimoto's thyroiditis are prevalent in between 13 and 34% of individuals with Down syndrome but only 3% of the neurotypical population, a pattern similarly recognized in individuals with Celiac Disease (5.8% v 0.5-2%), alopecia areata (27.7% v. 2%), and vitiligo (4.4% v. 0.05-1.55%), respectively. Given the chronicity of autoimmune conditions, early identification and management can significantly impact the quality of life of individuals with Down syndrome. This comprehensive review will highlight common clinical autoimmune conditions observed in individuals with Down syndrome and explore our current understanding of the mechanisms of disease in this population.

De novo variants in immune regulatory genes in Down syndrome regression disorder.

BACKGROUND: Down Syndrome Regression Disorder (DSRD) is a rare and poorly understood disorder of the central nervous system, characterized by acute or subacute neuropsychiatric symptoms in previously healthy individuals with Down syndrome (DS). Many patients exhibit immunotherapy-responsiveness, indicative of immune dysregulation as a potential underlying etiology. While hypotheses are emerging regarding the role of interferon signaling in DSRD and other autoimmune conditions associated with DS, it is unclear why a small subset of individuals with DS develop DSRD. The aim of this study was to investigate genes of immune regulation in persons with DSRD. METHODS: This study included individuals with DSRD aged 10-30 years with trio exome sequencing performed during the diagnostic work up. Descriptive statistics and univariate analysis (Chi-square and Fisher's exact test) were used to describe and compare the characteristics of individuals with and without variants. RESULTS: Forty-one individuals with DSRD had trio exome sequencing results. Eight (20%) had heterozygous de novo variants of immune regulatory genes, with four variants being pathogenic or likely pathogenic (UNC13D, XIAP, RNASEH2A, and DNASE1L3). All genes harboring pathogenic variants were associated with interferon type-1 inflammatory response. Individuals harboring variants were more likely to have a preceding trigger (p = 0.03, 95% CI 1.21-97.06), rapid clinical decline in less than 1 month (p = 0.01, 95% CI 1.67-52.06), and MRI abnormalities (p < 0.001, 95% CI 4.89-527.71). DISCUSSION: A distinct subset of individuals with DSRD exhibited pathogenic variants in immune regulation genes associated with interferon-mediated inflammatory response, coinciding with previously established links between these genes and interferonopathies such as Aicardi-Goutieres syndrome. Our observations suggest that these variants might potentially contribute to the development of DSRD in individuals with DS.

Patient Perception of Physician Reimbursement by Medicare for Artificial Urinary Sphincter Placement.

INTRODUCTION: Patient perceptions of physician reimbursement commonly differ from actual reimbursement. This study aims to improve health care cost transparency and trust between patients, physicians, and the health care system by evaluating patient perceptions of Medicare reimbursement for artificial urinary sphincter (AUS) placement. METHODS: We identified patients who underwent AUS placement at a single institution from 2014 to 2023. After obtaining informed consent, we administered a telephone survey to ask patients about their perceptions of Medicare reimbursement for AUS surgery and the amount they felt the physician should be compensated. RESULTS: Sixty-four patients were enrolled and completed the survey. On average, patients estimated Medicare physician reimbursement to be $18,920, 25 times the actual average procedure reimbursement. Once informed that the actual amount was $757.52, 97% of respondents felt that the reimbursement was "somewhat lower" (13%) or "much lower" (84%) than what they considered fair. The average amount that patients felt the physician should be paid was $8,844, 12 times the actual average procedure reimbursement. Fifty-four percent of patients estimated their physician's reimbursement to be higher than what they later reported as being "fair," representing a presurvey belief that their physician was overpaid. CONCLUSIONS: Patient perceptions of physician reimbursement for AUS are vastly different than the actual amount paid. The discordance between patient perception and actual reimbursement could impact how patients view health care costs and the relationship with their provider.

Urinary and Oral Microbiota Among Men Undergoing Buccal Urethroplasty.

OBJECTIVE: To assess changes in the urinary microbiota after buccal urethroplasty. METHODS: At the University of California San Francisco, we enrolled 9 adult males with urethral strictures undergoing buccal urethroplasty where we collected urine and oral swabs intraoperatively and 3 months postoperatively. 16S rRNA sequencing was used to profile the microbiota. RESULTS: At baseline, the mouth contains twice the number of unique bacteria (alpha diversity) and the microbial community is significantly distinct compared to the urinary tract. Despite having a buccal mucosa in the urinary tract after urethroplasty, the number of unique bacteria in the urine remained stable. However, the bacterial community composition and structure significantly changed in the urinary tract with the enrichment of Corynebacterium genus at 3 months post-urethroplasty procedure. CONCLUSION: In this pilot study, we showed that the alpha diversity in the urinary microbiota did not significantly change despite having a buccal tissue with the capacity to support high bacterial diversity in the urinary tract. To our surprise, the post-urethroplasty urinary microbiota was not a hybrid of baseline oral and urine microbiotas; the changes detected, such as an enrichment of the Corynebacterium genus, were more nuanced yet could profoundly impact surgical outcomes like graft changes and stricture recurrence. Our study not only established the feasibility but also outlined a blueprint for conducting a large-scale study to assess alterations in the urinary microbiome in relation to surgical outcomes.

Recapitulating the tumor microenvironment in a dish, one cell type at a time.

The tumor microenvironment harbors a variety of different cell types that differentially impact tumor biology. In this issue of Cell Reports Methods, Raffo-Romero et al. standardized and optimized 3D tumor organoids to model the interactions between tumor-associated macrophages and tumor cells in vitro.

A Multicenter Evaluation of Treatment-associated Changes in Body Composition in Men With Germ Cell Tumors of the Testis: Implications for Adverse Events and Complications.

OBJECTIVE: To characterize changes in body composition following cytotoxic chemotherapy for germ cell carcinoma of the testis (GCT) and quantify associations between body composition metrics and chemotherapy-associated adverse events (AEs) and post-retroperitoneal lymph node dissection (RPLND) complications. MATERIALS AND METHODS: This retrospective multi-center study included 216 men with GCT treated with cytotoxic chemotherapy and/or RPLND (2005-2020). We measured body composition including skeletal muscle (SMI), visceral adipose (VAI,), subcutaneous adipose (SAI), and fat mass (FMI) indices on computed tomography. We quantified chemotherapy-associated changes in body composition and evaluated associations between body composition and incidence of grade 3 + AEs and post-RPLND complications on multivariable logistic regression analyses. RESULTS: One hundred and eighty-two men received a median of 3 cycles of cisplatin-based chemotherapy. Following chemotherapy, median change in SMI was -6% (P = <.0001), while VAI, SAI, and FMI increased by +13% (P = <.0001), +11% (P = <.0001), and +6% (P = <.0001), respectively. Seventy-nine patients (43%) experienced at least one grade 3 + AE. A decrease in SMI following chemotherapy was associated with increased risk of grade 3 + AEs (P = .047). One hundred and 3 men with a median age of 28.5 years (IQR 23-35.5) underwent RPLND of whom 22 (21.3%) experienced at least 1 grade 3 + post-RPLND complication. No baseline body composition metrics were associated with post-RPLND complications. CONCLUSION: In men with GCT of the testis, chemotherapy was associated with 6% loss of lean muscle mass and gains in adiposity. Lower skeletal muscle was associated with a higher incidence of chemotherapy-associated AEs. Body composition was not associated with the incidence of post-RPLND complications.