High Area Deprivation Index is Associated With Discharge to Foster Care in Pediatric Patients With Non-accidental Trauma.

BACKGROUND: Outcomes after non-accidental trauma (NAT) have been shown to be impacted by social determinants of health. Our study aims to investigate the association between NAT, patient demographics, neighborhood disadvantage as measured by the Area Deprivation Index (ADI), and patient disposition. METHODS: An 8-year retrospective chart review was conducted in pediatric patients presenting to our level I trauma center with suspected NAT. Patient demographics, ADI, injury severity score (ISS), Glasgow coma scale (GCS), length of stay, and discharge disposition were analyzed using univariate and multivariate techniques to evaluate associations between patient demographics, injury severity, and patient outcomes. RESULTS: A total of 84 patients were admitted with suspected NAT. Of our study population, 45% of patients were White and 26% were Black. Black children were overrepresented in this cohort compared to general population means, while White children were underrepresented (p < 0.05). Median ADI was 6.5 (IQR 4.0-8.0). Of our cohort, 65 patients were discharged home, and 18 patients to foster care. One patient in our cohort died. An ADI >6 was the only factor significantly associated with discharge to foster care. This association held on both univariate (OR 1.4; 95% CI 1.07-1.84, p = 0.02) and multivariate (OR 1.4; 95% CI 1.05-1.86, p = 0.02) analyses. CONCLUSION: Our study found that neighborhood disadvantage, as measured by ADI, is an independent predictor of discharge to foster care. Additionally, Black children remain over-represented in the NAT population referred to our institution, including those discharged to foster care. Efforts to address healthcare disparities and community-based NAT prevention and reunification programs are necessary. TYPE OF STUDY: Prognosis Study (Retrospective Case-Control Study). LEVEL OF EVIDENCE: Level III.

Deciphering the importance of culture pH on CD22 CAR T-cells characteristics.

BACKGROUND: Chimeric antigen receptor (CAR) T-cells have demonstrated significant efficacy in targeting hematological malignancies, and their use continues to expand. Despite substantial efforts spent on the optimization of protocols for CAR T-cell manufacturing, critical parameters of cell culture such as pH or oxygenation are rarely actively monitored during cGMP CAR T-cell generation. A comprehensive understanding of the role that these factors play in manufacturing may help in optimizing patient-specific CAR T-cell therapy with maximum benefits and minimal toxicity. METHODS: This retrospective study examined cell culture supernatants from the manufacture of CAR T-cells for 20 patients with B-cell malignancies enrolled in a phase 1/2 clinical trial of anti-CD22 CAR T-cells. MetaFLEX was used to measure supernatant pH, oxygenation, and metabolites, and a Bio-Plex assay was used to assess protein levels. Correlations were assessed between the pH of cell culture media throughout manufacturing and cell proliferation as well as clinical outcomes. Next-generation sequencing was conducted to examine gene expression profiles of the final CAR T-cell products. RESULTS: A pH level at the lower range of normal at the beginning of the manufacturing process significantly correlated with measures of T-cell expansion and metabolism. Stable or rising pH during the manufacturing process was associated with clinical response, whereas a drop in pH was associated with non-response. CONCLUSIONS: pH has potential to serve as an informative factor in predicting CAR T-cell quality and clinical outcomes. Thus, its active monitoring during manufacturing may ensure a more effective CAR T-cell product.

Validation of Cell-Free Protein Synthesis Aboard the International Space Station.

Cell-free protein synthesis (CFPS) is a rapidly maturing in vitro gene expression platform that can be used to transcribe and translate nucleic acids at the point of need, enabling on-demand synthesis of peptide-based vaccines and biotherapeutics as well as the development of diagnostic tests for environmental contaminants and infectious agents. Unlike traditional cell-based systems, CFPS platforms do not require the maintenance of living cells and can be deployed with minimal equipment; therefore, they hold promise for applications in low-resource contexts, including spaceflight. Here, we evaluate the performance of the cell-free platform BioBits aboard the International Space Station by expressing RNA-based aptamers and fluorescent proteins that can serve as biological indicators. We validate two classes of biological sensors that detect either the small-molecule DFHBI or a specific RNA sequence. Upon detection of their respective analytes, both biological sensors produce fluorescent readouts that are visually confirmed using a hand-held fluorescence viewer and imaged for quantitative analysis. Our findings provide insights into the kinetics of cell-free transcription and translation in a microgravity environment and reveal that both biosensors perform robustly in space. Our findings lay the groundwork for portable, low-cost applications ranging from point-of-care health monitoring to on-demand detection of environmental hazards in low-resource communities both on Earth and beyond.

A fluorescence viewer for rapid molecular assay readout in space and low-resource terrestrial environments.

Fluorescence-based assays provide sensitive and adaptable methods for point of care testing, environmental monitoring, studies of protein abundance and activity, and a wide variety of additional applications. Currently, their utility in remote and low-resource environments is limited by the need for technically complicated or expensive instruments to read out fluorescence signal. Here we describe the Genes in Space Fluorescence Viewer (GiS Viewer), a portable, durable viewer for rapid molecular assay readout that can be used to visualize fluorescence in the red and green ranges. The GiS Viewer can be used to visualize any assay run in standard PCR tubes and contains a heating element. Results are visible by eye or can be imaged with a smartphone or tablet for downstream quantification. We demonstrate the capabilities of the GiS Viewer using two case studies-detection of SARS-CoV-2 RNA using RT-LAMP and quantification of drug-induced changes in gene expression via qRT-PCR on Earth and aboard the International Space Station. We show that the GiS Viewer provides a reliable method to visualize fluorescence in space without the need to return samples to Earth and can further be used to assess the results of RT-LAMP and qRT-PCR assays on Earth.

Patient engagement in designing, conducting, and disseminating clinical pain research: IMMPACT recommended considerations.

ABSTRACT: In the traditional clinical research model, patients are typically involved only as participants. However, there has been a shift in recent years highlighting the value and contributions that patients bring as members of the research team, across the clinical research lifecycle. It is becoming increasingly evident that to develop research that is both meaningful to people who have the targeted condition and is feasible, there are important benefits of involving patients in the planning, conduct, and dissemination of research from its earliest stages. In fact, research funders and regulatory agencies are now explicitly encouraging, and sometimes requiring, that patients are engaged as partners in research. Although this approach has become commonplace in some fields of clinical research, it remains the exception in clinical pain research. As such, the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials convened a meeting with patient partners and international representatives from academia, patient advocacy groups, government regulatory agencies, research funding organizations, academic journals, and the biopharmaceutical industry to develop consensus recommendations for advancing patient engagement in all stages of clinical pain research in an effective and purposeful manner. This article summarizes the results of this meeting and offers considerations for meaningful and authentic engagement of patient partners in clinical pain research, including recommendations for representation, timing, continuous engagement, measurement, reporting, and research dissemination.

Antineoplastic activity of GP-2250 in-vitro and in mouse xenograft models.

This study examined the antineoplastic effects of GP-2250 (misetionamide), an oxathiazine derivative with broad activity, in multiple cancer cell lines and mouse xenograft models. Antineoplastic activity of GP-2250 was tested in >300 cancer cell lines using the OncoPanel cytotoxicity assay. GP-2250 activity was further tested in mouse xenograft models, in which GP-2250 or vehicle (10 ml/kg) was administered daily for 28 days by intraperitoneal injection in the lower right abdomen of CrTac:NCR-Foxn1nu mice with tumor volumes of 100 to 200 mm 3 . In the in-vitro models, GP-2250 increased cytotoxicity readings with IC50 and EC50 as well as indications of cell cycle blockage in pancreatic and ovarian cell lines. In mouse xenograft models, a reduction of 30-40% in tumor volume occurred in the GP-2250 group versus the vehicle group. On the final day of the study, tumor progression was significantly reduced in 4 tumor types: HT-29 in the GP-2250 500 and 1000 mg/kg groups, SKOV-3 in all GP-2250 treatment groups, Cal-27 in the GP-2250 1000 mg/kg group, and Hs-695T in the GP-2250 250 and 1000 mg/kg groups. Tumor regression in Cal-27 tumors was dose-dependent. GP-2250 demonstrated cytotoxic activity in vitro and reduced the tumor volume in a variety of human cancer cell lines in a xenograft mouse model. Given these results, as well as evidence of synergism with other anticancer drugs, GP-2250 shows promise as a new therapeutic agent for treating human cancers and is being evaluated in a phase 1 dose-escalation study (NCT03854100).

Assessment and comparison of viability assays for cellular products.

BACKGROUND AIMS: Accurate assessment of cell viability is crucial in cellular product manufacturing, yet selecting the appropriate viability assay presents challenges due to various factors. This study compares and evaluates different viability assays on fresh and cryopreserved cellular products, including peripheral blood stem cell (PBSC) and peripheral blood mononuclear cell (PBMC) apheresis products, purified PBMCs and cultured chimeric antigen receptor and T-cell receptor-engineered T-cell products. METHODS: Viability assays, including manual Trypan Blue exclusion, flow cytometry-based assays using 7-aminoactinomycin D (7-AAD) or propidium iodide (PI) direct staining or cell surface marker staining in conjunction with 7-AAD, Cellometer (Nexcelom Bioscience LLC, Lawrence, MA, USA) Acridine Orange/PI staining and Vi-CELL BLU Cell Viability Analyzer (Beckman Coulter, Inc, Brea, CA, USA), were evaluated. A viability standard was established using live and dead cell mixtures to assess the accuracy of these assays. Furthermore, precision assessment was conducted to determine the reproducibility of the viability assays. Additionally, the viability of individual cell populations from cryopreserved PBSC and PBMC apheresis products was examined. RESULTS: All methods provided accurate viability measurements and generated consistent and reproducible viability data. The assessed viability assays were demonstrated to be reliable alternatives when evaluating the viability of fresh cellular products. However, cryopreserved products exhibited variability among the tested assays. Additionally, analyzing the viability of each subset of the cryopreserved PBSC and PBMC apheresis products revealed that T cells and granulocytes were more susceptible to the freeze-thaw process, showing decreased viability. CONCLUSIONS: The study demonstrates the importance of careful assay selection, validation and standardization, particularly for assessing the viability of cryopreserved products. Given the complexity of cellular products, choosing a fit-for-purpose viability assay is essential.

Rapid anti-myeloma activity by T cells expressing an anti-BCMA CAR with a human heavy-chain-only antigen-binding domain.

Multiple myeloma (MM) is a rarely curable malignancy of plasma cells. MM expresses B cell maturation antigen (BCMA). We developed a fully human anti-BCMA chimeric antigen receptor (CAR) with a heavy-chain-only antigen-recognition domain, a 4-1BB domain, and a CD3ζ domain. The CAR was designated FHVH33-CD8BBZ. We conducted the first-in-humans clinical trial of T cells expressing FHVH33-CD8BBZ (FHVH-T). Twenty-five patients with relapsed MM were treated. The stringent complete response rate (sCR) was 52%. Median progression-free survival (PFS) was 78 weeks. Of 24 evaluable patients, 6 (25%) had a maximum cytokine-release syndrome (CRS) grade of 3; no patients had CRS of greater than grade 3. Most anti-MM activity occurred within 2-4 weeks of FHVH-T infusion as shown by decreases in the rapidly changing MM markers serum free light chains, urine light chains, and bone marrow plasma cells. Blood CAR+ cell levels peaked during the time that MM elimination was occurring, between 7 and 15 days after FHVH-T infusion. C-C chemokine receptor type 7 (CCR7) expression on infusion CD4+ FHVH-T correlated with peak blood FHVH-T levels. Single-cell RNA sequencing revealed a shift toward more differentiated FHVH-T after infusion. Anti-CAR antibody responses were detected in 4 of 12 patients assessed. FHVH-T has powerful, rapid, and durable anti-MM activity.

Debunking Myths of Gender Informed Care: What Every Pediatric Surgeon Should Know.

As the transgender population in the United States grows, gender-affirming care is becoming increasingly relevant to the practice of pediatric surgery. Medical care for the transgender and gender diverse population is a politically charged topic with significant complexity and opportunities for clarification. It is important for providers to better understand this population's unique health and social needs. This review aims to debunk long-standing myths regarding gender-affirming care and highlight the current therapeutic and legislative landscapes within the scope of pediatric surgical practice. LEVEL OF EVIDENCE: IV.

T cell activation is insufficient to drive SIV disease progression.

Resolution of T cell activation and inflammation is a key determinant of the lack of SIV disease progression in African green monkeys (AGMs). Although frequently considered together, T cell activation occurs in response to viral stimulation of acquired immunity, while inflammation reflects innate immune responses to mucosal injury. We dissociated T cell activation from inflammation through regulatory T cell (Treg) depletion with Ontak (interleukin-2 coupled with diphtheria toxin) during early SIV infection of AGMs. This intervention abolished control of T cell immune activation beyond the transition from acute to chronic infection. Ontak had no effect on gut barrier integrity, microbial translocation, inflammation, and hypercoagulation, despite increasing T cell activation. Ontak administration increased macrophage counts yet decreased their activation. Persistent T cell activation influenced SIV pathogenesis, shifting the ramp-up in viral replication to earlier time points, prolonging the high levels of replication, and delaying CD4+ T cell restoration yet without any clinical or biological sign of disease progression in Treg-depleted AGMs. Thus, by inducing T cell activation without damaging mucosal barrier integrity, we showed that systemic T cell activation per se is not sufficient to drive disease progression, which suggests that control of systemic inflammation (likely through maintenance of gut integrity) is the key determinant of lack of disease progression in natural hosts of SIVs.

Bringing the Walk with Ease Programme to the UK: a mixed-methods study to assess the relevance, acceptability, and feasibility of implementation for people with arthritis and musculoskeletal conditions.

Developed in the United States (US), Walk With Ease (WWE) is a popular evidence-based, 6-week community walking programme for adults with arthritis, delivered in either an instructor-led or self-directed format. While WWE has expanded into communities across the USA, it is relatively unknown in other countries across the globe. This study, in collaboration with community and patient partners, aimed to examine the relevance, acceptability and feasibility of introducing WWE into a UK context. After initial cultural adaptation, participants were recruited into the study. Eligible (≥18 years, doctor diagnosed arthritis (confirmed or self-report), self-reported joint symptoms in last 30 days, BMI ≥25 kg/m2, and <150 min/week of moderate/vigorous PA) and consented participants were randomized into two groups: WWE programme or usual care. A mixed-methods analysis approach integrated quantitative data (physical performance assessment; baseline and post-six week programme questionnaire) and qualitative data (narrative interviews exploring participants' pre- and post-WWE experiences and stakeholders' perceptions). Of 149 participants, the majority were women (70%) aged ≥60 years (76%). Among the 97 receiving the programme, 52 chose instructor-led; 45 chose self-directed. Participants found WWE relevant and acceptable-99% indicating they would recommend WWE to family/friends. Within both WWE formats, mixed differences representing improvement were observed at 6 weeks from baseline for physical performance and arthritis symptoms. Emergent themes included improved motivation, health, and social well-being. WWE is a relevant and acceptable walking programme with scope for wider implementation to support UK health and well-being policy strategies.

Walk With Ease (WWE) is a popular walking programme in the USA. It was specially designed for people living with arthritis and musculoskeletal conditions. Over 6-weeks, participants follow a guidebook and can choose to walk by themselves or with an instructor-led group. Research evidence has shown that WWE increases time spent being physically active and improves arthritis symptoms. We wanted to bring WWE across the pond to explore whether it would be well-received and possible to conduct in the UK. We worked with community and patient partners to make sure the WWE materials made sense for a British audience and trained walk leaders. We recruited participants and asked them to complete physical assessment tests, questionnaires, and interviews both before and after the 6-week walking programme. There were 149 participants who took part­most were older women­and 97 participants received the WWE programme. Almost all (99%) would recommend WWE to family and friends. They said, in the interviews, that the programme improved their motivation to be physically active, helped their mood, and social well-being. Their physical performance and arthritis symptoms also improved. WWE has great potential to improve health and well-being of people with arthritis in the UK.

Views of American Pediatric Surgeons on Diversity, Equity, and Inclusion.

INTRODUCTION: Diversity, Equity, and Inclusion (DEI) are concepts common in surgery. However, these can be difficult to define, and what constitutes DEI can be vague. Closing this knowledge gap, particularly within pediatric surgery, would be helpful to understand the views and needs of current surgeons. METHODS: 1558 APSA members were sent an anonymous survey, of which 423 (27%) responded. Respondents were asked about their demographics, views on what constitutes diversity as well as questions on how DEI is handled within APSA and definitions of common DEI terms. RESULTS: Of 11 possible diversity measures, members agreed that a median of 9 (IQR 7-11) counted towards diversity. The most common being race and ethnicity (98%), gender (96%), sexual orientation (93%), religion (92%), age (91%), and disability (90%). On a 5-point Likert scale, the median response was 4 or greater on questions regarding how APSA handles issues related to DEI. However, members who identify as black were less likely to score in favor of APSA, and members identifying as women were more likely to rank higher importance of DEI initiatives. We also captured subjective responses on DEI terminology. CONCLUSION: Respondents had broad definitions of diversity. There is support for further DEI initiatives and how APSA handles DEI, however this perception differs based on identities. There is significant variability in beliefs and views regarding DEI definitions and understanding this is helpful for the organization moving forward. LEVEL OF EVIDENCE: IV. TYPE OF STUDY: Original Research.

Calcaneal broadband ultrasound attenuation predicts physical capability: EPIC-Norfolk prospective population-based study.

BACKGROUND: Calcaneal ultrasound (broadband ultrasound attenuation - BUA), a marker of bone strength, may predict future physical capability and thus provide a strategy to identify individuals at risk of age-related deterioration of health. This study aims to determine if BUA can predict future physical capability among middle-aged and older adults. METHODS: Summary performance scores (SPS), an objective quantification of physical capability, were devised using participants' measures of standing balance, gait speed and timed chair rises. Associations between BUA and SPS, measured at least six years apart, were investigated using univariable and multivariate sex-specific linear and logistic regression, adjusting for confounders. RESULTS: 5893 participants were included. In men and women, for every five points lower BUA, there was a 0.2-point decrease in SPS. In women, BUA less than one standard deviation below the mean was associated with low physical capability (defined as SPS 3-6); fully adjusted odds ratio (OR) (95 % confidence interval (CI)) 1.35 (1.01-1.84). No association existed among men; OR (95 % CI) 0.84 (0.59-1.19). Significant risk factors for low physical capability in men with baseline low BUA were: older age [OR 5.77]; high BMI [OR 2.85]; lower social class [OR 1.59]; low physical activity [OR 1.64]. Risk factors among women were: older age [OR 5.54]; high BMI [OR 2.08]; lower education [OR 1.42], low physical activity [OR 1.27]; steroid use [OR 2.05]; and stroke [OR 2.74]. CONCLUSION: BUA may predict future physical capability in older adults. With further validation, BUA could stratify individuals at risk of deterioration in physical health.

Cervical Collar Clearance in Obtunded Children Presenting Without a Known Traumatic Mechanism: Is Imaging Necessary?

BACKGROUND: Obtunded pediatric patients are often placed in cervical collars (c-collars) to protect their cervical spine (c-spine) while injury is being ruled out, even without a known traumatic injury. The goal of this study was to determine the necessity of c-collars in this population by determining the rate of c-spine injury among patients with suspected non-traumatic mechanisms of loss of consciousness. METHODS: A single institution, ten-year retrospective chart review was conducted including all obtunded patients admitted to the Pediatric Intensive Care Unit without a known traumatic event. Patients were categorized into five groups based on etiology of obtundation: respiratory, cardiac, medical/metabolic, neurologic, and other. Comparisons were made between those placed in a c-collar and a control group who were not, using Wilcoxon rank sum test for continuous measures, and Chi-square or Fisher's exact test for categorical measures. RESULTS: 464 patients were included, of which 39 (8.41%) were placed in a c-collar. There was a significant difference in whether a patient was placed in a c-collar based on diagnosis category (p < 0.001). Those placed in a-c-collar were more likely to undergo imaging studies than the control group (p < 0.001). The overall incidence of c-spine injury in this patient population in our study was zero. CONCLUSION: Cervical collar placement and radiographic evaluation is not necessary in obtunded pediatric patients who present without a known traumatic mechanism as the overall risk of injury is low. Consideration for collar placement should be given in cases when trauma cannot be definitively ruled out at initial evaluation. LEVELS OF EVIDENCE: III.

Factors predicting the transition from acute to persistent pain in people with 'sciatica': the FORECAST longitudinal prognostic factor cohort study protocol.

INTRODUCTION: Sciatica is a common condition and is associated with higher levels of pain, disability, poorer quality of life, and increased use of health resources compared with low back pain alone. Although many patients recover, a third develop persistent sciatica symptoms. It remains unclear, why some patients develop persistent sciatica as none of the traditionally considered clinical parameters (eg, symptom severity, routine MRI) are consistent prognostic factors.The FORECAST study (factors predicting the transition from acute to persistent pain in people with 'sciatica') will take a different approach by exploring mechanism-based subgroups in patients with sciatica and investigate whether a mechanism-based approach can identify factors that predict pain persistence in patients with sciatica. METHODS AND ANALYSIS: We will perform a prospective longitudinal cohort study including 180 people with acute/subacute sciatica. N=168 healthy participants will provide normative data. A detailed set of variables will be assessed within 3 months after sciatica onset. This will include self-reported sensory and psychosocial profiles, quantitative sensory testing, blood inflammatory markers and advanced neuroimaging. We will determine outcome with the Sciatica Bothersomeness Index and a Numerical Pain Rating Scale for leg pain severity at 3 and 12 months.We will use principal component analysis followed by clustering methods to identify subgroups. Univariate associations and machine learning methods optimised for high dimensional small data sets will be used to identify the most powerful predictors and model selection/accuracy.The results will provide crucial information about the pathophysiological drivers of sciatica symptoms and may identify prognostic factors of pain persistence. ETHICS AND DISSEMINATION: The FORECAST study has received ethical approval (South Central Oxford C, 18/SC/0263). The dissemination strategy will be guided by our patient and public engagement activities and will include peer-reviewed publications, conference presentations, social media and podcasts. TRIAL REGISTRATION NUMBER: ISRCTN18170726; Pre-results.

Cost-effectiveness of cognitive behavioural and personalized exercise interventions for reducing fatigue in inflammatory rheumatic diseases.

OBJECTIVES: To estimate the cost-effectiveness of a cognitive behavioural approach (CBA) or a personalized exercise programme (PEP), alongside usual care (UC), in patients with inflammatory rheumatic diseases who report chronic, moderate to severe fatigue. METHODS: A within-trial cost-utility analysis was conducted using individual patient data collected within a multicentre, three-arm randomized controlled trial over a 56-week period. The primary economic analysis was conducted from the UK National Health Service (NHS) perspective. Uncertainty was explored using cost-effectiveness acceptability curves and sensitivity analysis. RESULTS: Complete-case analysis showed that, compared with UC, both PEP and CBA were more expensive [adjusted mean cost difference: PEP £569 (95% CI: £464, £665); CBA £845 (95% CI: £717, £993)] and, in the case of PEP, significantly more effective [adjusted mean quality-adjusted life year (QALY) difference: PEP 0.043 (95% CI: 0.019, 0.068); CBA 0.001 (95% CI: -0.022, 0.022)]. These led to an incremental cost-effectiveness ratio (ICER) of £13 159 for PEP vs UC, and £793 777 for CBA vs UC. Non-parametric bootstrapping showed that, at a threshold value of £20 000 per QALY gained, PEP had a probability of 88% of being cost-effective. In multiple imputation analysis, PEP was associated with significant incremental costs of £428 (95% CI: £324, £511) and a non-significant QALY gain of 0.016 (95% CI: -0.003, 0.035), leading to an ICER of £26 822 vs UC. The estimates from sensitivity analyses were consistent with these results. CONCLUSION: The addition of a PEP alongside UC is likely to provide a cost-effective use of health care resources.

Mechanism of Injury and Age Predict Operative Intervention in Pediatric Perineal Injury.

OBJECTIVES: Literature characterizing pediatric perineal trauma is sparse and generally limited to females. The purpose of this study was to characterize pediatric perineal injuries with specific focus on patient demographics, mechanisms of injury, and care patterns at a regional level 1 pediatric trauma center. METHODS: Retrospective review of children aged younger than 18 years evaluated at a level 1 pediatric trauma center from 2006 to 2017. Patients were identified by International Classification of Diseases-9 and 10 codes. Extracted data included demographics, injury mechanism, diagnostic studies, hospital course, and structures injured. The χ 2 and t tests were used to examine differences between subgroups. Machine learning was used to predict variable importance in determining the need for operative interventions. RESULTS: One hundred ninety-seven patients met inclusion criteria. Mean age was 8.5 years. A total of 50.8% were girls. Blunt trauma accounted for 83.8% of injuries. Motor vehicle collisions and foreign bodies were more common in patients aged 12 years and older, whereas falls and bicycle-related injuries were more common in those younger than 12 years ( P < 0.01). Patients younger than 12 years were more likely to sustain blunt trauma with isolated external genital injuries ( P < 0.01). Patients aged 12 and older had a higher incidence of pelvic fractures, bladder/urethral injuries, and colorectal injuries, suggesting more severe injury patterns ( P < 0.01). Half of patients required operative intervention. Children aged 3 years or younger and older than 12 years had longer mean hospital stays compared with children aged 4 to 11 years ( P < 0.01). Mechanism of injury and age constituted more than 75% of the variable importance in predicting operative intervention. CONCLUSIONS: Perineal trauma in children varies by age, sex, and mechanism. Blunt mechanisms are the most common, with patients frequently requiring surgical intervention. Mechanism of injury and age may be important in deciding which patients will require operative intervention. This study describes injury patterns in pediatric perineal trauma that can be used to guide future practice and inform injury prevention efforts.

Sex Difference in OA: Should We Blame Estrogen?

Osteoarthritis (OA) is a leading cause of chronic pain and disability, not only in the United States but also worldwide. The burden of OA is higher in women than in men. Estrogen as a possible explanation for observed sex differences in OA has not been definitively established. The purpose of this review was to summarize the results from studies of estrogen, estrogen depletion and treatment, and their impact on knee, hip, hand, and spine OA. We conducted a targeted review of the literature using PubMed. Although several studies show that hormone replacement therapy has the potential to be protective of OA for some joints, there are studies that showed no protective effect or even adverse effect. Taken together, the evidence for the protective effect of estrogen therapy depends on OA joint, OA outcome, and study design. Although this area has been studied for decades, more exclusively since the 1990s, there is a lack of high-quality experimental research in this topic. The lack of definitive conclusion on whether estrogen can play a role in the development in OA of either the knee, hip, spine, or hand is often in part due to the noncomparability of studies existing within the literature. Differences in diagnostic criteria, imaging modalities, populations studied, study designs, and outcome measures, as well as random error, have all contributed to inconclusive evidence. Future research on the role of estrogen in OA is needed, particularly as global demographic shifts in increasing overweight/obesity prevalence and ageing populations may contribute to widening OA-related health inequalities.

APSA Members experience bias and discrimination in training and practice.

INTRODUCTION: Bias and discrimination remain pervasive in the medical field and increase the risk of burnout, mental health disorders, and medical errors. The experiences of APSA members with bias and discrimination are unknown, therefore the APSA committee on Diversity, Equity and Inclusion conducted a survey to characterize the prevalence of bias and discrimination. METHODS: 1558 APSA members were sent an anonymous survey, of which 423 (27%) responded. Respondents were asked about their demographics, knowledge of implicit bias, and experience of bias and discrimination within their primary workplace, APSA, and APSA committees. Data were analyzed using Fisher's Exact test, Kruskal-Wallis test, and multivariable logistic regression as appropriate with significance defined as p<0.05. RESULTS: Discrimination was reported across all levels of practice, academic appointments, race, ethnicity, and gender identities. On multivariable analysis, surgical trainees (OR 3.6) as well as Asian American and Pacific Islander (OR 4.8), Black (OR 5.2), Hispanic (OR 8.2) and women (OR 8.7) surgeons were more likely to experience bias and discrimination in the workplace. Community practice surgeons were more likely to experience discrimination within APSA committees (OR 3.6). Members identifying as Asian (OR 0.4), or women (OR 0.6) were less likely to express comfort reporting instances of bias and discrimination. CONCLUSION: Workplace discrimination exists across all training levels, academic appointments, and racial and gender identities. Trainees and racial- and gender-minority surgeons report disproportionately high prevalence of bias and discrimination. Improving reporting mechanisms and implicit bias training are possible initiatives in addressing these findings.