Sex and racial disparities in living donor liver transplantation in the United States.

Sex and racial disparities in deceased donor liver transplantation (DDLT) have been described, but this has not been well studied in living donor liver transplantation (LDLT). We aim to examine these disparities in the US LDLT population and identify potential predictors of these differences. From 2002 to 2021, the Organ Procurement and Transplant Network database was queried to characterize the adult LDLT population and evaluate differences between LDLT and DDLT recipients with regard to sex and race. Donor demographics, Model for End-stage Liver Disease (MELD), and socioeconomic data were all included. Of the 4961 LDLT and 99,984 DDLT recipients, males received the majority of LDLT (55% vs. 45%, p < 0.001) and DDLT (67% vs. 33%, p < 0.001) compared to females. There was a significant difference in race between male and female LDLT recipients ( p < 0.001); 84% of male recipients were White and 78% of females. In both groups, females had lower levels of education and were less likely to have private insurance. There were more female living donors (N = 2545, 51%); 50% of female donors donated to males but only 40% of males donated to females. Donor-recipient relationships varied significantly by sex ( p < 0.001); males received more donations from spouses (62% vs. 39%) and siblings (60% vs. 40%). In the LDLT population, significant disparities exist with respect to sex and race that disadvantage women, but these disparities are less pronounced than in the DDLT population. Although further studies are needed, complex clinical and socioeconomic differences as well as donor factors may explain these variations.

NSG-Pro mouse model for uncovering resistance mechanisms and unique vulnerabilities in human luminal breast cancers.

Most breast cancer deaths are caused by estrogen receptor-α­positive (ER+) disease. Preclinical progress is hampered by a shortage of therapy-naïve ER+ tumor models that recapitulate metastatic progression and clinically relevant therapy resistance. Human prolactin (hPRL) is a risk factor for primary and metastatic ER+ breast cancer. Because mouse prolactin fails to activate hPRL receptors, we developed a prolactin-humanized Nod-SCID-IL2Rγ (NSG) mouse (NSG-Pro) with physiological hPRL levels. Here, we show that NSG-Pro mice facilitate establishment of therapy-naïve, estrogen-dependent PDX tumors that progress to lethal metastatic disease. Preclinical trials provide first-in-mouse efficacy of pharmacological hPRL suppression on residual ER+ human breast cancer metastases and document divergent biology and drug responsiveness of tumors grown in NSG-Pro versus NSG mice. Oncogenomic analyses of PDX lines in NSG-Pro mice revealed clinically relevant therapy-resistance mechanisms and unexpected, potently actionable vulnerabilities such as DNA-repair aberrations. The NSG-Pro mouse unlocks previously inaccessible precision medicine approaches for ER+ breast cancers.

The impact of risk factors on gastroparesis at an urban medical center.

BACKGROUND: Gastroparesis is a complex and poorly understood disease. The literature is lacking with respect to the epidemiology of patient comorbidities and their effect on gastric emptying. We aimed to describe the most common comorbid conditions among patients with gastroparesis in an urban population and quantify the effect of these comorbidities on the severity of delayed gastric emptying (DGE). METHODS: We examined the medical records of all patients diagnosed with gastroparesis at a quaternary care center between 2014 and 2015. The severity of DGE was analyzed after patients were stratified for possible causative etiologies. Likelihood ratio tests were used to assess the significance of demographic and scintigraphic variation in this population. RESULTS: Of the 221 patients, 56.1% were Caucasian and 31.7% were African American. Among these patients, 29.4% had evidence of medication-associated gastroparesis, 29.0% had diabetes-associated gastroparesis, and 31.7% had idiopathic disease. African American patients with gastroparesis were more likely to have diabetic gastroparesis than patients of other races (P=0.01). There was a statistically significant relationship between the number of major risk factors and the severity of a patient's DGE (P=0.004). CONCLUSIONS: Among a diverse urban population, patients with DGE often carry multiple comorbid conditions that serve as risk factors for the development of gastroparesis, including prescriptions for narcotic medications. Greater numbers of these comorbid conditions are associated with more severe disease. Demographics are significantly associated with the etiology and severity of gastroparesis; in particular, African American patients are more likely to have diabetic gastroparesis than patients of other races.