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Introduction Studies focused on rural–urban disparities in patients with prostate cancer have demonstrated minimal differences in incidence and overall survival (OS). However, available data are limited, especially in understudied geographic locations. In this study, we investigated additional measures of potential cancer disparity and focused on examining rural–urban prostate cancer disparity in Nebraska residents. Methods Patients diagnosed with prostate cancer from 1991 to 2023 living in Nebraska were identified in the integrated Cancer Repository for Cancer Research (iCaRe2) and categorized as rural and urban by rural–urban commuting area (RUCA) codes. Results Results are presented as mean ± standard deviation. The iCaRe2 patient registry contained data on 765 men with prostate cancer living in Nebraska, 621 (81.2%) of whom were urban residents and 144 (18.8%) of whom were rural residents. Rural residents were diagnosed with prostate cancer 3.1 years younger than urban residents (rural: 65.6 ± 8.21 years, urban: 68.7 ± 9.08 years, p < 0.001). Rural residents died of prostate cancer 4.2 years younger than urban residents (rural: 72.9 ± 9.75 years, urban: 77.1 ± 8.85 years, p < 0.001). Analyses of Gleason score and AJCC stage did not reveal statistically significant differences between rural and urban residents. OS was similar between rural and urban men in Nebraska with prostate cancer, congruent with currently published literature. Conclusions Our analysis demonstrates that rural patients in Nebraska are diagnosed and die with prostate cancer at younger ages compared to urban patients. Our findings offer strategies to better define and delineate rural–urban cancer disparity and support future, more robust investigations to consider novel approaches to determining disparities in cancer disease course.

Blocked or narrowed arteries restrict blood flow to the lower limbs, commonly leading to peripheral artery disease (PAD). Patients with PAD have been shown to have increased gait variability, which may contribute to higher rates of falls and worsen functional outcomes. Surgical revascularization seeks to restore blood flow to the legs, but it is unknown if this restoration enhances limb function. This study investigated whether gait variability changes in patients with PAD after revascularization surgery. Thirty-three patients with PAD exhibiting claudication symptoms were recruited for the study. Kinematic data were recorded using a motion capture system while the patients walked on a treadmill following a progressive treadmill protocol, both before and after undergoing revascularization surgery. Angular sagittal movements’ linear and nonlinear variability in the lower limbs were measured and compared before and after surgery across the ankle, knee, and hip joints. Following revascularization surgery, knee joint sample entropy (SampEn) decreased, suggesting improved gait regularity. Furthermore, the hip range of motion (ROM) significantly decreased, whereas the knee ROM significantly increased. The ankle joint showed significantly greater changes in the Lyapunov Exponent (LyE) relative to the pre-exercise condition compared with the hip and knee joints. No significant differences existed in the linear variability (standard deviation) of the ROM between joints. In individuals with PAD, revascularization surgery considerably increased knee ROM and gait regularity, indicating improved limb function and motor control. However, the ankle ROM remained unchanged, indicating the need for targeted strengthening exercises post-surgery.

Background: Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are common diseases affecting millions worldwide. These two diseases have a complex relationship that is not well understood. Previous small studies suggest an inverse relationship of disease severity of OSA with COPD airflow obstruction. Objective: The aim of this study was to determine if a relationship exists between severity of airflow obstruction in COPD and severity of OSA via apnea hypopnea index obtained during an in-lab baseline polysomnogram using a large quaternary care center cohort. Methods: From November 2015 through December 2018, 273 patients with confirmed COPD via spirometry and OSA via in-lab baseline polysomnogram were included. Conclusion: No associations were noted between severity of airflow obstruction in COPD and disease severity of OSA. Given the heterogeneity of these diseases, further exploration of a relationship within disease subtypes is warranted. Keywords: airflow obstruction, chronic obstructive pulmonary disease, obstructive sleep apnea

This study investigated the impact of walking with ankle-foot-orthoses (AFOs) and without AFOs (non-AFO) on ground reaction forces (GRFs) in patients with peripheral artery disease (PAD). Additionally, this study examined the effect of AFO intervention vs. no AFO intervention on GRFs while walking with and without AFOs. Fifty patients with PAD were randomly assigned to either a three-month intervention (AFO) or a control (standard-of-care) group. After three months, subjects crossed over to the alternate group and were evaluated after three additional months. GRF data (anterior-posterior, medial-lateral, and vertical) were collected during walking with and without AFOs at baseline, three, and six months. Peak discrete GRF points, braking and propulsion impulses were compared across conditions, groups, and time points using linear mixed models. The peak brake and propulsion GRF were significantly reduced while walking with AFOs versus non-AFO (p < 0.01). Compared to non-AFO, walking with AFOs significantly reduced lateral GRF magnitude (p = 0.03) and significantly increased medial GRF (p = 0.02). The first and second maximum (p < 0.01) vertical GRF were significantly increased with AFOs versus non-AFOs. Walking with AFOs helped patients with PAD achieve greater peak propulsion and vertical GRFs compared to non-AFO, with GRF values trending toward those previously reported in healthy individuals.

Accurate diagnosis of melanomas is crucial for proper evaluation and treatment. One immunohistochemical stain frequently utilized is PRAME (PReferentially expressed Antigen in MElanoma), a tumor-associated antigen expressed in most melanomas. This study aims to evaluate the reproducibility of PRAME scoring performed by dermatopathologists at an academic tertiary referral medical center. A blinded survey was designed featuring 21 melanocytic neoplasms stained with PRAME and H&E. For each case, five dermatopathologists provided a PRAME score from 0–4+, percent PRAME positivity, values for H-score, and a descriptive interpretation. Absolute agreement across raters was assessed using a Kappa statistic for PRAME score and intraclass correlations (ICCs) for H-score and PRAME percentage. Statistical analysis indicated poor inter-rater reliability for PRAME score (Kappa = 0.16), percent PRAME positivity (ICC = 0.31), and H-score (ICC = 0.40). Reporting language varied among pathologists. Our study demonstrated that the interpretation of PRAME immunohistochemistry lacks reproducibility, especially for challenging lesions. This suggests that a more rigorous, defined, and reproducible scoring method should be investigated for equivocal cases. Future studies may explore the utility of artificial intelligence software in the interpretation of PRAME for borderline lesions to improve reliability and standardize scoring.

Competent physicians must be able to self-assess skill level; however, previous studies suggest that medical trainees may not accurately self-assess. We utilized Pathology Milestones (PM) data to determine whether there were discrepancies in self- versus Clinical Competency Committee (CCC) ratings by sex, program year (PGY), time of evaluation, and question category (Patient Care, Medical Knowledge, Systems-Based Practice [SBP], Practice-Based Learning and Improvement [PBL], Professionalism [PRO], and Interpersonal and Communication Skills) and Residency In-Service Examination (RISE) score. We completed retrospective analyses of PM evaluation scores from 2016 to 2019 (n = 23 residents) 2 times per year. Discrepancies in evaluation scores were calculated by subtracting CCC scores from resident self-evaluation scores. There was no significant difference in discrepancy scores between male versus female residents (P = .94). Discrepancy scores among all PGYs were significantly different (P < .0001), with PGY1 tending to overrate the most, followed by PGY2. PGY3 and PGY4 underrated themselves on average compared to CCC ratings, with PGY4 having significantly lower self-ratings than CCC compared to any other PGY. In January, residents underscored themselves and in July residents overscored themselves compared to CCC (P < .0001 for both). Question types resulted in variable discrepancy scores, with SBP significantly lower than and PRO significantly higher than all other categories (P < .05 for both). Increases in RISE score correlated to increases in self- and CCC-scoring. These discrepancies can help trainees improve self-assessment. Discrepancies indicate potential areas for amelioration, such as curriculum adjustments or Milestone’s verbiage.

•Down-staging of cervical cancer has occurred over the study period.•Cervical cancer incidence increased prior to 2006, after which is plateaued.•Cervical cancer mortality has slightly increased over the study period.•In recent years, the second most common stage of diagnosis was stage III. In most developed countries, incidence of cervical cancer declined likely due to well-established cervical cancer screening programs. However, such decline has not been identified in Eastern Europe, where such programs are not well established. This study utilized data of the Bulgarian Cancer Registry for the period 1993–2013. Age-standardized incidence and mortality trends were analyzed using Joinpoint regression. Maps were created to illustrate spatial distributions of rates. The northern region of Bulgaria showed a larger cervical cancer burden than the southern region and rural women tended to be diagnosed at older ages (p<0.0001) and later stages (p<0.0001) than urban women. The distribution of disease stages changed over the 21 years, with most common stages of diagnosis being stage II in 1993 (39.2%) to stage I in 2013 (44.7%; p<0.0001). While age-standardized mortality slightly increased over the 21 years (from 4.8 to 5.2 per 100,000; p=0.009), age-standardized incidence increased from 14.0 to 21.4 per 100,000 up until 2006 (p<0.001), after which it plateaued. The lack of a similar plateau in mortality may be because the second most prevalent stage of diagnosis in recent years was stage III, indicating diagnosis at advanced symptomatic stages. Cervical cancer incidence is expected to continue to decrease if screening programs are strengthened and human papillomavirus vaccines are widely utilized. As Bulgaria has shared cervical cancer trends with other Eastern European countries in the past, it may be beneficial to develop future prevention interventions based on a regional, rather than a country-specific level.

Introduction: Tobacco control laws that raise the minimum age of tobacco sales to 21 years (T21) play a pivotal role in youth tobacco prevention, yet empirical data are sorely needed to inform enforcement, compliance efforts, and future legislation. Methods: Spatial analysis was conducted at the zip code level by geocoding the states and localities that adopted T21 ordinances from 2015 to 2019. A multi-level logistic regression model was conducted to examine disparities in neighborhood socioeconomic status (SES), FDA retail inspection, and state-level tobacco control policies associated with T21 adoption. Results: T21 adoption at the state and local level increased considerably from 1.4% of zip codes in 2015 to 40.2% in 2019. However, the T21 ordinances were disproportionally adopted in New England (82.6%) and Pacific (73.6%) regions with scarce coverage in East South Central (< 0.1%), Mountain (1.6%), and West North Central regions (6.1%). The T21 policies were more likely to be adopted in areas with stronger tobacco control policies, urban areas (vs rural, adjusted odds ratio, AOR=1.25, p=0.005), areas with a larger Hispanic (AOR=1.19, p< 0.0001) or Asian population (AOR=1.12, p< 0.0001), and in areas where the population had higher levels of education (AOR=1.05, p< 0.0001). It was less likely to be adopted in areas with larger proportions of American Indians, youths, and young adults. Nearly 40% of zip codes with tobacco retailers did not receive annual FDA tobacco retail inspections for underage sales in 2019. The average retail violation rate of underage sales of tobacco products in T21 regions was lower than in non-T21 regions. Conclusions: Disparities in T21 adoption, retail inspections, and retail compliance may limit the policy impact. Unified enforcement of youth tobacco access restrictions with resources and interventions in vulnerable communities is needed to reduce tobacco-related health disparities.

Higher therapeutic concentrations of the antiseizure medication carbamazepine (CBZ) are associated with cognitive side effects. Hippocampal sharp wave-ripple complexes (SPW-Rs) are proposed to participate in memory consolidation during periods of quiet and slow-wave sleep. SPW-Rs are generated in the CA3 region and are regulated by multiple synaptic inputs. Here, we used a multi-electrode array to determine the effects of CBZ on SPW-Rs and synaptic transmission at multiple hippocampal synapses. Our results demonstrate that CBZ reduced SPW-Rs at therapeutically relevant concentrations (IC50 = 37 μM) and altered the core characteristics of ripples, important for information processing and consolidation. Moreover, CBZ inhibited neurotransmission in a synapse-specific manner. CBZ inhibition was most potent at the medial-perforant-path-to-CA3 and mossy-fiber-to-CA3 synapses (IC50s ~ 30 and 60 μM, respectively) and least potent at medial-perforant-path-to-dentate granule cell synapses (IC50 ~ 120 μM). These results suggest that the synapse-specific CBZ inhibition of neurotransmission reduces SPW-Rs and that the CBZ inhibition of SPW-Rs may underlie the cognitive impairments observed with therapeutic doses of CBZ.

Background: Sepsis is a major cause of mortality worldwide. Early identification and treatment are critical to improve survival. Band count has been used as part of SIRS criteria for the early identification of potentially septic patients. Unfortunately, band count requires manual interpretation. This leads to increased potential for intraobserver variability. Immature granulocytes are counted in an automated fashion, which has the potential to improve accuracy and reduce costs.Research Objective: We aim to compare the band percentage and immature granulocyte percentage to set the threshold for immature granulocyte percentage equal to the sensitivity of > 10% band count.Methods: A retrospective chart review was conducted at a single academic medical center. Data from patients with SIRS criteria and measured immature granulocyte and band percentages were utilized to explore potential associations between immature granulocyte percentages and band percentages. Data were analyzed using Spearman correlations, Wilcoxon rank-sum tests, and logistic regressions.Results: We found no significant associations between immature granulocyte percentage and band percentage or other SIRS criteria.Conclusion: We conclude that immature granulocyte percentage does not correlate with band percentage in the setting of possible infection.