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Background/Objectives: Colorectal cancer remains a significant global health challenge, particularly in resource-limited settings where patient-centered outcomes following surgery are often suboptimal. Although more prevalent in low- and middle-income countries (LMICs), segments of the United States have similarly limited healthcare resources, resulting in stark inequities even within close geographic proximity. Methods: This review compares and contrasts colorectal cancer outcomes in LMICs with those in resource-constrained communities in rural America, utilizing an established implementation science framework to identify key determinants of practice for delivering high-quality colorectal cancer care. Results: Barriers and innovative, community-based strategies aimed at improving patient-centered outcomes for colorectal cancer patients in low resource settings are identified. We explore innovative approaches and community-based strategies aimed at improving patient-centered outcomes, highlighting the newly developed colorectal surgery fellowship in Sub-Saharan Africa as a model of innovation in this field. Conclusions: By exploring these diverse contexts, this paper proposes actionable solutions and strategies to enhance surgical care of colorectal cancer and patient outcomes, ultimately aiming to inform global health practices, inspire collaboration between LMIC and rural communities, and improve care delivery across various resource settings.

We sought to evaluate common leadership experiences and academic achievements obtained by current U.S. Medical School Deans of Medicine (DOMs) prior to their first appointment as Dean in order to elucidate a common pathway for promotion. In April-June 2019 the authors requested a curriculum vitae from each of the 153 LCME-accredited U.S. Medical School DOMs. The authors abstracted data on prior appointments, demographics, and achievements from CVs and online databases. Differences by gender and institutional rank were then evaluated by the Fisher's exact and Wilcoxon rank sum tests. CVs were obtained for 62% of DOMs (95 of 153), with women comprising 16% of the responding cohort (15/95). Prior to appointment as DOM, 34% of respondents had served as both permanent Department Chair and Associate Dean, 39% as permanent Department Chair but not Associate Dean, and 17% as Associate Deans but not permanent Department Chair. There was a non-significant trend for men to have been more likely to have been a permanent Department Chair (76% vs 53%, p = 0.11) and less likely to have been an Associate Dean (48% vs 67%, p = 0.26) compared to women. Responding DOMs at Top-25 research institutions were mostly male (15/16), more likely to have been appointed before 2010 (38% vs 14%, p = 0.025), and had higher H-indices (mean (SD): 73.1 (32.3) vs 33.5 (22.5), p<0.01) than non-Top-25 Deans. The most common pathway to DOM in this study cohort was prior service as Department Chair. This suggests that diversification among Department Chair positions or expansion of search criteria to seek leaders from pools other than Department Chairs may facilitate increased diversity, equity, and inclusion among DOM overall.

Organs suitable for donation are a scarce resource and maximizing the use of available organs is a priority. We aimed to determine whether there is a supply restricting left digit bias in organs offered and accepted for donors entering a new decade of age. Potential deceased organ donors (n = 105,387) who had any organs offered for transplantation from 2010 to 2019 Organ Procurement and Transplantation Network data were analyzed. Donors were identified 1 year before and after a decade altering birthday. At age 70 there was a 5.4% decrease in the probability of any organ placement compared to 69 (95% CI 1.1–9.7). There was a decrease of 0.25 organs (95% CI 0.13–0.37) after age 70. There was a significant left digit bias in the acceptance of any organs for transplantation at ages 60 and 70 as well as in the acceptance of a kidney at age 70. •There was a decrease in the probability of any organ placement for donors at age 70 compared to 69.•After a donor's 70th birthday there was a decrease in number of organs placed.•These findings represent a left digit bias in the evaluation of donor organs that restricts the supply of available organs.

To explore persisting gender disparities across leadership roles in medicine, we examined factors associated with holding endowed chairs in US oncology divisions. In 2019, we identified 95 academic oncology divisions, using the Oncology Division Chiefs and Department Chairs listing in the American Society of Clinical Oncology myConnection forum. We collected public information on gender, degree, total National Institutes of Health funding as principal investigator, H-indices, publication and citation numbers, and graduation year and constructed a multivariable logistic regression model. All statistical tests were 2-sided. We identified 1087 oncology full professors. Of these, 287 (26.4%) held endowed chairs: 60 of 269 women (22.3%) vs 227 of 818 men (27.8%) (P = .08). On multivariable analysis, greater research productivity and National Institutes of Health funding were associated with having an endowed chair (P < .001), whereas gender was not (P = .45). Though sample size was limited, if gender differences are in fact smaller in certain subspecialties than other fields of internal medicine, insights might emerge to guide efforts to promote equity.

This study examined US kidney transplant center websites for readability and for inclusion of languages other than English.

Efforts to develop a range of HIV prevention products that can serve as behaviorally congruent viable alternatives to consistent condom use and oral pre-exposure prophylaxis (PrEP) remain crucial. MTN-035 was a randomized crossover trial seeking to evaluate the safety, acceptability, and adherence to three placebo modalities (insert, suppository, enema) prior to receptive anal intercourse (RAI). If participants had no RAI in a week, they were asked to use their assigned product without sex. We hypothesized that the modalities would be acceptable and safe for use prior to RAI, and that participants would report high adherence given their behavioral congruence with cleansing practices (e.g., douches and/or enemas) and their existing use to deliver medications (e.g., suppositories; fast-dissolving inserts) via the rectum. Participants (N = 217) were sexual and gender minorities enrolled in five different countries (Malawi, Peru, South Africa, Thailand, and the United States of America). Mean age was 24.9 years (range 18–35 years). 204 adverse events were reported by 98 participants (45.2%); 37 (18.1%) were deemed related to the study products. The proportion of participants reporting “high acceptability” was 72% (95%CI: 65% - 78%) for inserts, 66% (95%CI: 59% - 73%) for suppositories, and 73% (95%CI: 66% - 79%) for enemas. The proportion of participants reporting fully adherent per protocol (i.e., at least one use per week) was 75% (95%CI: 69% - 81%) for inserts, 74% (95%CI: 68% - 80%) for suppositories, and 83% (95%CI: 77% - 88%) for enemas. Participants fully adherent per RAI-act was similar among the three products: insert (n = 99; 58.9%), suppository (n = 101; 58.0%) and enema (n = 107; 58.8%). The efficacy and effectiveness of emerging HIV prevention drug depends on safe and acceptable delivery modalities that are easy to use consistently. Our findings demonstrate the safety and acceptability of, and adherence to, enemas, inserts, and suppositories as potential modalities through which to deliver a rectal microbicide.

Hyposmia is one of the most prevalent non-motor symptoms of Parkinson’s disease and antecedes motor dysfunction by up to a decade. However, the underlying pathophysiology remains poorly understood. In this study, we investigated the mechanisms of dopamine metabolism in post-mortem olfactory bulbs from ten Parkinson’s disease and ten neurologic control subjects. In contrast to the loss of dopaminergic neurons in the midbrain, we observed an increase in tyrosine hydroxylase-positive neurons in the Parkinson’s disease olfactory bulb, suggesting a potential role for dopamine in the hyposmia associated with the condition. Using immunohistochemistry, high-performance liquid chromatography, western blot, and enzyme-linked immunosorbent assays, we demonstrate a reduction in catechol- O -methyltransferase catabolism of dopamine to homovanillic acid, potentially due to a depletion of the methyl donor substrate S -adenosyl methionine. We hypothesized that reduction in catechol- O -methyltransferase activity would result in increased dopamine occupation of the D 2 receptor, and consequent inhibition of olfactory processing. Next, we conducted pharmacological interventions to modify dopamine dynamics in hyposmic tau knockout mice, which exhibit altered dopamine metabolism. Our hypothesis was supported by the observation that the D 2 receptor antagonist haloperidol temporarily alleviated olfactory deficits in these tau knockout mice. This study implicates a potential role of catechol- O -methyltransferase-mediated dopamine metabolism in the early olfactory impairments associated with Parkinson’s disease.

Nicholas Katsanis and colleagues report that a common allele of RPGRIP1L is associated with photoreceptor loss in ciliopathies. An A229T variant in RPGRIP1L compromises binding to RPGR and modifies the retinal degeneration phenotype in ciliopathies caused by mutations in other genes. Despite rapid advances in the identification of genes involved in disease, the predictive power of the genotype remains limited, in part owing to poorly understood effects of second-site modifiers. Here we demonstrate that a polymorphic coding variant of RPGRIP1L (retinitis pigmentosa GTPase regulator-interacting protein-1 like), a ciliary gene mutated in Meckel-Gruber (MKS) and Joubert (JBTS) syndromes, is associated with the development of retinal degeneration in individuals with ciliopathies caused by mutations in other genes. As part of our resequencing efforts of the ciliary proteome, we identified several putative loss-of-function RPGRIP1L mutations, including one common variant, A229T. Multiple genetic lines of evidence showed this allele to be associated with photoreceptor loss in ciliopathies. Moreover, we show that RPGRIP1L interacts biochemically with RPGR, loss of which causes retinal degeneration, and that the Thr229-encoded protein significantly compromises this interaction. Our data represent an example of modification of a discrete phenotype of syndromic disease and highlight the importance of a multifaceted approach for the discovery of modifier alleles of intermediate frequency and effect.