LX1 Targets Androgen Receptor Variants and AKR1C3 to overcome Therapy Resistance in Advanced Prostate Cancer.

The development of resistance to current standard-of-care treatments, such as androgen receptor (AR) targeting therapies, remains a major challenge in the management of advanced prostate cancer. There is an urgent need for therapeutic strategies targeting key resistance drivers, such as AR variants like AR-V7 and steroidogenic enzymes like AKR1C3, to improve outcomes for patients with advanced prostate cancer. Here, we designed, synthesized, and characterized a class of LX compounds targeting both AR/AR variants and AKR1C3. Molecular docking indicated that LX compounds bound to the AKR1C3 active sites. LX1 blocked AKR1C3 enzymatic activity, suppressing the conversion of androstenedione into testosterone. LX compounds also reduced AR/AR-V7 expression and downregulated their target genes. In vitro, LX1 inhibited the growth of prostate cancer cells resistant to antiandrogens, including enzalutamide, abiraterone, apalutamide, and darolutamide. Treatment with LX1 in vivo significantly decreased tumor growth, lowered serum PSA levels, and reduced intratumoral testosterone levels, without affecting mouse body weight. Furthermore, LX1 overcame resistance to enzalutamide treatment, and the combination of LX1 with enzalutamide further suppressed tumor growth. Collectively, the dual effect of LX1 in reducing intratumoral testosterone and AR signaling, along with its synergy with standard therapies in resistant models, underscores its potential as a valuable treatment option for advanced prostate cancer.

Associations Between PTSD Features and Firearm Ownership and Storage: Results From the PRImary Care Screening Methods (PRISM) Study.

INTRODUCTION: Veterans and active duty service members are significantly more likely to die by suicide using firearms compared to the general population. Not-secure firearm storage (e.g., keeping guns loaded/in an unlocked location) is associated with greater risk for suicide and a third of veteran firearm owners store at least 1 personal firearm unsecured. Veterans and active duty service members are also significantly more likely to be diagnosed with posttraumatic stress disorder (PTSD) than the general population. Symptoms of PTSD are divided into 4 criteria: reexperiencing, avoidance, negative affect, and hyperarousal. Research has suggested that endorsement of hyperarousal symptoms is positively associated with unsecure firearm storage and that avoidance symptoms might be negatively associated with unsecure storage practices. The present study examined the relationship between self-reported firearm ownership and storage practices among each item from the Primary Care PTSD Screening for DSM-IV-TR (PC-PTSD-IV) to explore associations between PTSD features and firearm ownership and storage. MATERIALS AND METHODS: Participants were recruited from primary care clinics across 5 military installations in the United States as part of a larger study (Mage = 45.4, SD = 16.9). Among participants (n = 2,685), most of our sample identified as male (51.3%) and white (67.3%) with 61.6% currently serving in the military, 16.8% retirees, and 21.6% family members. PTSD symptoms were assessed using the PC-PTSD-IV and a quarter met the clinical threshold for PTSD. Binomial and multinomial logistic regression analyses were used. RESULTS: Among completed responses, 989 (38.1%) people reported owning guns; among gun owners, 386 (39.0%) reported that they were loaded, and 352 (35.6%) reported they were loaded and unlocked. Endorsement of specific items on the PC-PTSD-IV, including those specific to hyperarousal and avoidance, was not significantly associated with storing firearms loaded and/or in nonsecure locations when controlling for military service. Non-responses to items around firearm storage practices were significantly associated with those individuals meeting the clinical threshold for PTSD according to the PC-PTSD-IV and participants currently serving had higher odds of storing at least 1 personal firearm loaded and both loaded and unlocked. CONCLUSIONS: Results from our study highlight similarities and departures from the previous literature on the connection between PTSD and non-secure firearm storage practices. Further research may examine (1) the relation between PTSD symptoms and firearm storage between active duty service members, retirees, and family members and (2) whether non-response to items regarding firearm ownership is systematic.

Tournament Recovery Profiles and Physical Demands in a Collegiate Women's Tennis Team.

ABSTRACT: Tendero-Ortiz, E, Johnson, MJ, Horsfall, CM, Vondrasek, JD, Grosicki, GJ, Riemann, BL, and Flatt, AA. Tournament recovery profiles and physical demands in a collegiate women's tennis team. J Strength Cond Res XX(X): 000-000, 2024-We aimed to characterize recovery profiles and tournament physical demands in women's collegiate tennis players. A Division 1 team (n = 9) participated in the study. Markers of cardiac autonomic (resting heart rate [HR], HR variability), neuromuscular (isometric handgrip strength, seated single-arm shot-put test [SSAPT], hexagon agility, countermovement jump characteristics), and perceptual recovery were obtained before the tournament (baseline) and again 1 and 2 days posttournament. Cardiorespiratory (HR) and movement characteristics from matches were quantified with wearable devices. p values < 0.05 were statistically significant. No recovery markers differed from baseline (ps > 0.05), although small effect size reductions 1 day posttournament were noted for SSAPT, hexagon agility, and select countermovement jump characteristics. In addition, hexagon agility times and SSAPT were slower (p < 0.01) and shorter (p < 0.05), respectively, at 1 versus 2 days posttournament. Similarly, relative to 1 day posttournament, perceptual makers were improved 2 days posttournament (ps < 0.05). Mean and peak HR were higher for singles versus doubles matches  (ps < 0.05). Except for average speed, movement parameters were greater during singles versus doubles matches (ps < 0.05). Markers of recovery were minimally affected 1 day posttournament relative to baseline, but perceptual and select neuromuscular markers were most improved 2 days posttournament. Thus, passive rest or limited intensity training 1 day posttournament seems advisable. Competition HR and movement profiles inform practitioners of the cardiorespiratory and locomotor demands of women's collegiate tennis, which may be useful in designing preparatory conditioning programs to ensure that players attain match-specific physical capacities in training before competition.

The Role of Local Flaps in Foot and Ankle Reconstruction: An Assessment of Outcomes Across 206 Patients with Chronic Wounds.

BACKGROUND: Reconstructive surgery has experienced a paradigm shift in favor of free flaps. Yet, local flaps may be of particular use in foot and ankle reconstruction among comorbid patient populations. Thus, we sought to better characterize long-term outcomes in this setting. METHODS: A single-center, retrospective cohort study of patients undergoing local muscle and fasciocutaneous flaps of the foot and ankle from January 2010-November 2022 was performed. Flap were performed on wounds measuring 3x6cm or smaller, and flap selection depended on preoperative vascular assessment, Doppler findings, comorbidity profile, and wound location, depth, and geometry. RESULTS: Two-hundred and six patients met inclusion criteria. Median age was 61.0 years (IQR 16.8), and comorbidities included diabetes mellitus (DM; n=149/206, 72.3%) and peripheral arterial disease (PAD; n=105/206, 51.0%). Presentations included chronic, non-healing wounds (n=77/206, 39.1%) or osteomyelitis (n=45/206, 22.8%), and most frequently extended to the bone (n=128/206, 62.1%). Eighty-seven patients (n=87/206, 42.2%) received muscle flaps, while 119 received fasciocutaneous flaps (n=119/206, 57.8%). Six patients (n=6/206, 2.9%) necessitated return to the operating room, with thrombosis occurring in two cases (n=2/206, 1.0%). Flap success rate was 98.1%. By a median follow-up duration of 21.7 months (IQR 39.0), 45 patients (n=45/206, 21.8%) necessitated ipsilateral amputation, 73% (n=145/199) were ambulatory, and two deaths were related to the operated wound (n=2/49, 4.1%). Multivariate analysis revealed positive predictors of complications included DM, end-stage renal disease, and prior histories of venous thromboembolism or smoking. CONCLUSION: Local flaps remain a reliable option to reconstruct smaller defects of the foot and ankle in a highly comorbid population.

Gut microbial ß-glucuronidases influence endobiotic homeostasis and are modulated by diverse therapeutics.

Hormones and neurotransmitters are essential to homeostasis, and their disruptions are connected to diseases ranging from cancer to anxiety. The differential reactivation of endobiotic glucuronides by gut microbial ß-glucuronidase (GUS) enzymes may influence interindividual differences in the onset and treatment of disease. Using multi-omic, in vitro, and in vivo approaches, we show that germ-free mice have reduced levels of active endobiotics and that distinct gut microbial Loop 1 and FMN GUS enzymes drive hormone and neurotransmitter reactivation. We demonstrate that a range of FDA-approved drugs prevent this reactivation by intercepting the catalytic cycle of the enzymes in a conserved fashion. Finally, we find that inhibiting GUS in conventional mice reduces free serotonin and increases its inactive glucuronide in the serum and intestines. Our results illuminate the indispensability of gut microbial enzymes in sustaining endobiotic homeostasis and indicate that therapeutic disruptions of this metabolism promote interindividual response variabilities.

Clines of resistance to parasitoids: the multifarious effects of temperature on defensive symbioses in insects.

Insects are frequently infected with heritable bacterial endosymbionts. Some of them confer resistance to parasitoids. Such defensive symbionts are sensitive to variation in temperature. Drawing predominantly from the literature on aphids and flies, we show that temperature can affect the reliability of maternal transmission and the strength of protection provided by defensive symbionts. Costs of infection with defensive symbionts can also be temperature-dependent and may even turn into benefits under extreme temperatures, for example, when defensive symbionts increase heat tolerance. Alone or in combination, these mechanisms can drive temperature-associated (latitudinal) clines of infection prevalence with defensive symbionts. This has important consequences for host-parasitoid coevolution, as the relative importance of host-encoded vs. symbiont-provided defenses will shift along such clines.

Extruded alginate tubes with myogenic potential.

BACKGROUND: There are currently no proven methods to reverse muscle loss in humans, which is caused by trauma (e.g., volumetric muscle loss, VML), genetic neuromuscular diseases (e.g., muscular dystrophies, MDs), and accelerated senescence (e.g., sarcopenia). Since muscle tissue is capable of regeneration through muscle satellite cells (MuSCs), the implantation of autologous (or other) donor MuSCs and MuSC-derived myoblasts into host muscles can promote donor-cell-derived myogenesis. Direct injection or implantation of MuSCs or MuSC-derived myoblasts into host muscles only promotes minimal donor-cell-derived myogenesis, whereas implantation of MuSCs/myoblasts along with associated muscle tissue (muscle fibers, extracellular matrix, neurovascular pathways, etc.) gives better results. METHODS: We aim to leverage the benefits of constraining donor myogenic cells within a template that resembles muscle tissue. In this paper, we present a workflow for basic and translational studies aimed at promoting donor-cell-derived myogenesis to increase functional muscle mass in mice. Our workflow involves preparing a slurry of 10% sodium alginate mixed with myogenic cells in cell culture media, extruding the cell-containing slurry into 10% calcium lactate to form tubes, and implanting the cellularized alginate tubes into host muscle. RESULTS: Our data suggest that, the extruded alginate tubes can tolerate a peak stress of 1892 ± 527 mN, that the elastic range is at ~75-125% strain beyond initial length, and that the Young's modulus (stiffness) is 14.17 ± 1.68 %/mm2. Importantly, these mechanical properties render the alginate tubes suitable for a published technique known as minimally-invasive muscle embedding (MIME) that was developed by us to implant myogenic material into host muscle. MIME involves threading donor myogenic tissue into a needle track created within a host muscle. Cellularized alginate tubes implanted into the tibialis anterior muscle of previously euthanized mice had numerous hematoxylin-stained structures similar to nuclear staining, supporting the idea that our alginate tubes can support cell seeding. Alginate tubes that were seeded with MuSCs, incubated in MuSC/myoblast growth (i.e., proliferation) media for two days, incubated in myotube differentiation media for six days, and then minced and reseeded in new dishes, were able to promote in vitro myoblast outgrowth over several days. DISCUSSION: This pilot study is limited in its translational scope because it was performed in vitro and with previously euthanized mice. Additional studies are needed to confirm that cellularized alginate tubes can promote the de novo development of donor-cell-derived muscle fibers, which can contribute to contractile force production. CONCLUSION: Alginate tubes with MuSC/myoblasts can be generated by a simple extrusion method. The alginate tubes have sufficient mechanical strength to tolerate insertion into a host muscle, in a minimally-invasive manner, through a needle track. The cellularized alginate tubes demonstrate myogenic potential since they are capable of being maintained in culture conditions for several days, after which they can still facilitate myoblast outgrowth in a dish.

A Multidisciplinary Approach to End-Stage Limb Salvage in the Highly Comorbid Atraumatic Population: An Observational Study.

Background: The use of free tissue transfer (FTT) is efficacious for chronic, non-healing lower extremity (LE) wounds. The four pillars of managing patient comorbidities, infection control, blood flow status, and biomechanical function are critical in achieving successful limb salvage. The authors present their multidisciplinary institutional experience with a review of 300 FTTs performed for the complex LE limb salvage of chronic LE wounds. Methods: A single-institution, retrospective review of atraumatic LE FTTs performed by a single surgeon from July 2011 to January 2023 was reviewed. Data on patient demographics, comorbidities, preoperative management, intraoperative details, flap outcomes, postoperative complications, and long-term outcomes were collected. Results: A total of 300 patients who underwent LE FTT were included in our retrospective review. Patients were on average 55.9 ± 13.6 years old with a median Charlson Comorbidity Index of 4 (IQR: 3). The majority of patients were male (70.7%). The overall hospital length of stay (LOS) was 27 days (IQR: 16), with a postoperative LOS of 14 days (IQR: 9.5). The most prevalent comorbidities were diabetes (54.7%), followed by peripheral vascular disease (PVD: 35%) and chronic kidney disease (CKD: 15.7%). The average operative LE FTT time was 416 ± 115 min. The majority of flaps were anterolateral thigh (ALT) flaps (52.7%), followed by vastus lateralis (VL) flaps (25.3%). The immediate flap success rate was 96.3%. The postoperative ipsilateral amputation rate was 12.7%. Conclusions: Successful limb salvage is possible in a highly comorbid patient population with a high prevalence of diabetes mellitus, peripheral vascular disease, and end-stage renal disease. In order to optimize patients prior to their LE FTT, extensive laboratory, arterial, and venous preoperative testing and diabetes management are needed preoperatively. Postoperative monitoring and long-term follow-up with a multidisciplinary team are also crucial for long-term limb salvage success.

The urban lives of green sea turtles: Insights into behavior in an industrialized habitat using an animal-borne camera.

The cryptic and aquatic life histories of sea turtles have made them a challenging group to directly observe, leaving significant knowledge gaps regarding social behavior and fine-scale elements of habitat use. Using a custom-designed animal-borne camera, we observed previously undocumented behaviors by green turtles (Chelonia mydas) at a foraging area in San Diego Bay, a highly urbanized ecosystem in California, USA. We deployed a suction-cup-attached pop-off camera (manufactured by Customized Animal Tracking Solutions) on 11 turtles (mean straight carapace length = 84.0 ± 11.2 cm) for between 1 and 30.8 h. Video recordings, limited to sunlit hours, provided 73 h of total observation time between May 2022 and June 2023. We observed 32 conspecific interactions; we classified 18 as active, entailing clear social behaviors, as compared with 14 passive interactions representing brief, chance encounters. There was no evidence for agonistic interactions. The camera additionally revealed that green turtles consistently use metal structures within urban San Diego Bay. In seven instances, turtles exhibited rubbing behavior against metal structures, and we observed two examples of turtles congregating at these structures. High rates of intraspecific interaction exhibited relatively consistently among individuals provide a compelling case for sociality for green turtles in San Diego Bay, adding to a growing research base updating their historical label of "non-social." The frequent use of metal structures by the population, in particular the rubbing of exposed skin, has implications for behavioral adaptations to urban environments. Our study exemplifies the promise of technological advances (e.g., underwater and animal-borne cameras) for updating natural history paradigms, even for well-studied populations.

Survival outcomes in pediatric patients with metastatic Ewing sarcoma who achieve a rapid complete response of pulmonary metastases.

PURPOSE: Our objectives were to compare overall survival (OS) and pulmonary relapse between patients with metastatic Ewing sarcoma (EWS) at diagnosis who achieve rapid complete response (RCR) and those with residual pulmonary nodules after induction chemotherapy (non-RCR). PATIENTS AND METHODS: This retrospective cohort study included children under 20 years with metastatic EWS treated from 2007 to 2020 at 19 institutions in the Pediatric Surgical Oncology Research Collaborative. Chi-square tests were conducted for differences among groups. Kaplan-Meier curves were generated for OS and pulmonary relapse. RESULTS: Among 148 patients with metastatic EWS at diagnosis, 61 (41.2%) achieved RCR. Five-year OS was 71.2% for patients who achieved RCR, and 50.2% for those without RCR (p = .04), and in multivariable regression among patients with isolated pulmonary metastases, RCR (hazards ratio [HR] 0.42; 95% confidence interval [CI]: 0.17-0.99) and whole lung irradiation (WLI) (HR 0.35; 95% CI: 0.16-0.77) were associated with improved survival. Pulmonary relapse occurred in 57 (37%) patients, including 18 (29%) in the RCR and 36 (41%) in the non-RCR groups (p = .14). Five-year pulmonary relapse rates did not significantly differ based on RCR (33.0%) versus non-RCR (47.0%, p = .13), or WLI (38.8%) versus no WLI (46.0%, p = .32). DISCUSSION: Patients with EWS who had isolated pulmonary metastases at diagnosis had improved OS if they achieved RCR and received WLI, despite having no significant differences in rates of pulmonary relapse.

Primary peritoneal clear cell carcinoma arising in the setting of abdominal wall Endometriosis: A case report and review of the literature.

•Primary peritoneal clear cell carcinoma can arise from endometriotic implants within the abdomen and pelvis.•Immunohistochemistry can be used to confirm primary disease site. Endometriotic origin can be inferred based on clinical history and intraoperative findings suggestive of endometriosis.•While no standardized treatment exists, consideration should be given to cytoreductive surgery with adjuvant chemotherapy. Adjuvant radiation can also be considered for local control.

Evaluation of the X-ray/EUV Nanolithography Facility at AS through wavefront propagation simulations.

Synchrotron light sources can provide the required spatial coherence, stability and control to support the development of advanced lithography at the extreme ultraviolet and soft X-ray wavelengths that are relevant to current and future fabricating technologies. Here an evaluation of the optical performance of the soft X-ray (SXR) beamline of the Australian Synchrotron (AS) and its suitability for developing interference lithography using radiation in the 91.8 eV (13.5 nm) to 300 eV (4.13 nm) range are presented. A comprehensive physical optics model of the APPLE-II undulator source and SXR beamline was constructed to simulate the properties of the illumination at the proposed location of a photomask, as a function of photon energy, collimation and monochromator parameters. The model is validated using a combination of experimental measurements of the photon intensity distribution of the undulator harmonics. It is shown that the undulator harmonics intensity ratio can be accurately measured using an imaging detector and controlled using beamline optics. Finally, the photomask geometric constraints and achievable performance for the limiting case of fully spatially coherent illumination are evaluated.

Variable parallelism in the genomic basis of age at maturity across spatial scales in Atlantic Salmon.

Complex traits often exhibit complex underlying genetic architectures resulting from a combination of evolution from standing variation, hard and soft sweeps, and alleles of varying effect size. Increasingly, studies implicate both large-effect loci and polygenic patterns underpinning adaptation, but the extent that common genetic architectures are utilized during repeated adaptation is not well understood. Sea age or age at maturation represents a significant life history trait in Atlantic Salmon (Salmo salar), the genetic basis of which has been studied extensively in European Atlantic populations, with repeated identification of large-effect loci. However, the genetic basis of sea age within North American Atlantic Salmon populations remains unclear, as does the potential for a parallel trans-Atlantic genomic basis to sea age. Here, we used a large single-nucleotide polymorphism (SNP) array and low-coverage whole-genome resequencing to explore the genomic basis of sea age variation in North American Atlantic Salmon. We found significant associations at the gene and SNP level with a large-effect locus (vgll3) previously identified in European populations, indicating genetic parallelism, but found that this pattern varied based on both sex and geographic region. We also identified nonrepeated sets of highly predictive loci associated with sea age among populations and sexes within North America, indicating polygenicity and low rates of genomic parallelism. Despite low genome-wide parallelism, we uncovered a set of conserved molecular pathways associated with sea age that were consistently enriched among comparisons, including calcium signaling, MapK signaling, focal adhesion, and phosphatidylinositol signaling. Together, our results indicate parallelism of the molecular basis of sea age in North American Atlantic Salmon across large-effect genes and molecular pathways despite population-specific patterns of polygenicity. These findings reveal roles for both contingency and repeated adaptation at the molecular level in the evolution of life history variation.

A Case of Varicella Zoster and Mpox Coinfection in a Patient Living With HIV.

ABSTRACT: We present a case of recurrent, cutaneous mpox with coinfection of disseminated varicella zoster in an immunocompromised patient with poorly controlled HIV. This case demonstrates the importance of maintaining a high index of suspicion for mpox despite prior infection and vaccination, as suboptimal immune response is possible in immunocompromised patients, and also noting the potential for coinfection necessitating timely diagnosis and appropriate testing.

IGFBP3 promotes resistance to Olaparib via modulating EGFR signaling in advanced prostate cancer.

Olaparib is a pioneering PARP inhibitor (PARPi) approved for treating castration-resistant prostate cancer (CRPC) tumors harboring DNA repair defects, but clinical resistance has been documented. To study acquired resistance, we developed Olaparib-resistant (OlapR) cell lines through chronic Olaparib treatment of LNCaP and C4-2B cell lines. Here, we found that IGFBP3 is highly expressed in acquired (OlapR) and intrinsic (Rv1) models of Olaparib resistance. We show that IGFBP3 expression promotes Olaparib resistance by enhancing DNA repair capacity through activation of EGFR and DNA-PKcs. IGFBP3 depletion enhances efficacy of Olaparib by promoting DNA damage accumulation and subsequently, cell death in resistant models. Mechanistically, we show that silencing IGFBP3 or EGFR expression reduces cell viability and resensitizes OlapR cells to Olaparib treatment. Inhibition of EGFR by Gefitinib suppressed growth of OlapR cells and improved Olaparib sensitivity, thereby phenocopying IGFBP3 inhibition. Collectively, our results highlight IGFBP3 and EGFR as critical mediators of Olaparib resistance.

Epidermoid Cyst in the Submandibular Region Mimicking Plunging Ranula: A Case Report.

Epidermoid cysts rarely present in the submandibular area, constituting approximately less than 7% of all cystic lesions in the head and neck region and less than 0.01% of all oral cavity cysts. Therefore, epidermoid cysts can be easily misdiagnosed, as the differential diagnosis for a submandibular area mass is very broad. Imaging can help define characteristics of the mass; however, a pathologic specimen is usually required for the final diagnosis. Surgical excision is often required and tolerated well by most patients. However, there is a risk of recurrence of the cyst after excision, as well as a rare chance for malignant transformation if not excised, which must be discussed with the patient at the time of diagnosis of epidermoid cyst. We present a 33-year-old Caucasian female with a left submandibular cystic mass measuring 4.7 cm x 2.9 cm, that was originally thought to be a plunging ranula and subsequently diagnosed as an epidermoid cyst. This report is meant to raise awareness of the possibility of a submandibular mass being an epidermoid cyst as well as appropriate workup, treatment, and prognosis of epidermoid cysts in the submandibular region. This report also describes a unique approach to a submandibular epidermoid cyst of which the submandibular gland is divided for access to the cyst for safe and effective excision. To the author's knowledge, this surgical approach has not been described in the literature for a submandibular epidermoid cyst.

The impact of COVID-19 on racial and ethnic disparities in presentation with perforated appendicitis in children: A retrospective cohort study.

Background: Children from racial and ethnic minority groups have higher prevalence of perforated appendicitis, and the COVID-19 pandemic worsened racial and ethnic health-related disparities. We hypothesized that the incidence of perforated appendicitis worsened for children from racial and ethnic minorities during the COVID-19 pandemic. Methods: We performed a retrospective cohort study of the Pediatric Health Information System for children ages 2-18y undergoing appendectomy pre-pandemic (3/19/2019-3/18/2020) and intra-pandemic (3/19/2020-3/30/2021). The primary outcome was presentation with perforated appendicitis. Multivariable logistic regression with mixed effects estimated the likelihood of presentation with perforated appendicitis. Covariates included race, ethnicity, pandemic status, Child Opportunity Index, gender, insurance, age, and hospital region. Results: Overall, 33,727 children underwent appendectomy: 16,048 (47.6 %) were Non-Hispanic White, 12,709 (37.7 %) were Hispanic, 2261 (6.7 %) were Non-Hispanic Black, 960 (2.8 %) were Asian, and 1749 (5.2 %) Other. Overall perforated appendicitis rates were unchanged during the pandemic (37.4 % intra-pandemic, 36.4 % pre-pandemic, p = 0.06). Hispanic children were more likely to present with perforated appendicitis intra-pandemic versus pre-pandemic (OR 1.18, 95%CI: 1.07, 1.13). Hispanic children had higher odds of perforated appendicitis versus Non-Hispanic White children pre-pandemic (OR 1.10, 95%CI: 1.00, 1.20) which increased intra-pandemic (OR 1.19, 95%CI: 1.09, 1.30). Publicly-insured children had increased odds of perforated appendicitis intra-pandemic versus pre-pandemic (OR 1.14, 95%CI: 1.03, 1.25), and had increased odds of perforated appendicitis versus privately-insured children (intra-pandemic OR 1.26, 95%CI: 1.16, 1.36; pre-pandemic OR 1.12, 95%CI: 1.04, 1.22). Conclusions: During the COVID-19 pandemic, Hispanic and publicly-insured children were more likely to present with perforated appendicitis, suggesting that the pandemic exacerbated existing disparities in healthcare for children with appendicitis. Key message: We found that Hispanic children and children with public insurance were more likely to present with perforated appendicitis during the COVID-19 pandemic. Public health efforts aimed at ameliorating racial and ethnic disparities created during the COVID-19 pandemic should consider increasing healthcare access for Hispanic children to address bias, racism, and systemic barriers that may prevent families from seeking care.

The Impact of Prescription Drug Coverage on Disparities in Adherence and Medication Use: A Systematic Review.

Prescription drug cost-sharing is a barrier to medication adherence, particularly for low-income and minority populations. In this systematic review, we examined the impact of prescription drug cost-sharing and policies to reduce cost-sharing on racial/ethnic and income disparities in medication utilization. We screened 2,145 titles and abstracts and identified 19 peer-reviewed papers that examined the interaction between cost-sharing and racial/ethnic and income disparities in medication adherence or utilization. We found weak but inconsistent evidence that lower cost-sharing is associated with reduced disparities in adherence and utilization, but studies consistently found that significant disparities remained even after adjusting for differences in cost-sharing across individuals. Study designs varied in their ability to measure the causal effect of policy or cost-sharing changes on disparities, and a wide range of policies were examined across studies. Further research is needed to identify the types of policies that are best suited to reduce disparities in medication adherence.