Pulmonary Hypertension in Underrepresented Minorities: A Narrative Review.

Minoritized racial and ethnic groups suffer disproportionately from the incidence and morbidity of pulmonary hypertension (PH), as well as its associated cardiovascular, pulmonary, and systemic conditions. These disparities are largely explained by social determinants of health, including access to care, systemic biases, socioeconomic status, and environment. Despite this undue burden, minority patients remain underrepresented in PH research. Steps should be taken to mitigate these disparities, including initiatives to increase research participation, combat inequities in access to care, and improve the treatment of the conditions associated with PH.

Association of Reduced Hospitalizations and Mortality Rates Among COVID-19-Vaccinated Patients With Heart Failure.

BACKGROUND: Patients with heart failure (HF) are at high risk for adverse outcomes when they have COVID-19. Reports of COVID-19 vaccine-related cardiac complications may contribute to vaccine hesitancy in patients with HF. METHODS: To analyze the impact of COVID-19 vaccine status on clinical outcomes in patients with HF, we conducted a retrospective cohort study of the association of COVID-19 vaccination status with hospitalizations, intensive care unit admission and mortality after adjustment for covariates. Inverse probability treatment-weighted models were used to adjust for potential confounding. RESULTS: Of 7094 patients with HF, 645 (9.1%) were partially vaccinated, 2200 (31.0%) were fully vaccinated, 1053 were vaccine-boosted (14.8%), and 3196 remained unvaccinated (45.1%) by January 2022. The mean age was 73.3 ± 14.5 years, and 48% were female. Lower mortality rates were observed in patients who were vaccine-boosted, followed by those who were fully vaccinated; they experienced lower mortality rates (HR 0.33; CI 0.23, 0.48) and 0.36 (CI 0.30, 0.43), respectively, compared to unvaccinated individuals (P< 0.001) over the mean follow-up time of 276.5 ± 104.9 days, whereas no difference was observed between those who were unvaccinated or only partially vaccinated. CONCLUSION: COVID-19 vaccination was associated with significant reduction in all-cause hospitalization rates and mortality rates, lending further evidence to support the importance of vaccination implementation in the high-risk population of patients living with HF.

Barriers to Follow Up Care in the South Asian Immigrant Population at High Risk of Acute Coronary Syndrome at Elmhurst Hospital Center.

We studied South Asian immigrant patients who did not return to Elmhurst Hospital Center (EHC) after emergent cardiac catheterization in order to propose interventions to improve follow up care. We identified 74 eligible patients, interviewed 30 about follow up practices, and analyzed findings. Most patients are Bangladeshi and 77% preferred a foreign language. Some were visiting the US during the admission without intent to follow up. Half were dissatisfied with EHC providers, complications, and inadequate care at follow up appointments. Some patients were unaware of scheduled appointments or the necessity of follow up. Most follow with private providers due to language accessibility, availability, and proximity. We found that language barriers contribute to loss to follow up and the true loss to follow up rate is lower than reported at EHC. This can inform practices at hospitals with immigrant populations, minimize resource waste, and improve quality of care.

Survival of Patients With Gastroenteropancreatic Neuroendocrine Tumors and Diabetes Mellitus.

OBJECTIVES: Diabetes mellitus (DM) is associated with an increased risk of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), but the association between DM and GEP-NET survival is unknown. We evaluated disease characteristics and survival in individuals with DM and GEP-NETs. METHODS: Using the Surveillance, Epidemiology, and End Results registry linked to Medicare (SEER-Medicare) claims database, we examined sociodemographics, GEP-NET characteristics, and treatment in patients with and without DM before GEP-NET diagnosis. We compared survival using univariate and multivariate analyses. RESULTS: We identified 1858 individuals with GEP-NETs: 478 (25.7%) with DM and 1380 (74.3%) without. Significant differences in race (P = 0.002) were found between the DM and non-DM groups. Compared with individuals without DM, those with DM had more gastric (9.7% vs 14.9%), duodenal (6.5% vs 10.0%), and pancreatic (17.0% vs 21.8%), and less jejunal/ileal (18.1% vs 12.8%) NETs (P < 0.0001). Patients with DM had earlier stages (stage I, 37.0%; stage IV, 30.8%) than those without (stage I, 30.6%; stage IV, 36.4%; P = 0.0012). We found no difference in survival (multivariate hazard ratio, 0.97; 95% confidence interval, 0.76-1.23) between groups. CONCLUSIONS: Among patients with and without DM before GEP-NET diagnosis, we found differences in tumor location and stage, but not survival.

Effect of treatment center volume on outcomes in gastroenteropancreatic neuroendocrine tumor patients.

BACKGROUND: Medical centers with varying levels of expertise treat gastroenteropancreatic neuroendocrine tumors (GEP-NETs), which are relatively rare tumors. This study assesses the impact of center volume on GEP-NET treatment outcomes. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) registry linked to Medicare claims data. The data includes patients diagnosed between 1995 and 2010 who had no health maintenance organization (HMO) coverage, participated in Medicare parts A and B, were older than 65 at diagnosis, had tumor differentiation information, and had no secondary cancer. We identified medical centers at which patients received GEP-NET treatment (surgery, chemotherapy, somatostatin analogues, or radiation therapy) using Medicare claims data. Center volume was divided into 3 tiers - low, medium, and high - based on the number of unique GEP-NET patients treated by a medical center over 2 years. We used Kaplan-Meier curves and Cox regression to assess the association between volume and disease-specific survival. RESULTS: We identified 899 GEP-NET patients, of whom 37, 45, and 18% received treatment at low, medium volume, and high-volume centers, respectively. Median disease-specific survival for patients at low and medium tiers were 1.4 years and 5.3 years, respectively, but was not reached for patients at high volume centers. Results showed that patients treated at high volume centers had better survival than those treated in low volume centers (HR: 0.63, 95% CI: 0.4-0.9), but showed no difference in outcomes between medium and high-volume centers. CONCLUSIONS: Our results suggest that for these increasingly common tumors, referral to a tertiary care center may be indicated. Physicians caring for GEP-NET patients should consider early referral to high volume centers.

Recovery from secondary adrenal insufficiency in a patient with immune checkpoint inhibitor therapy induced hypophysitis.

BACKGROUND: Hypophysitis is a well-recognized immune-related adverse event in patients treated with immune checkpoint inhibitors for cancer. Some anterior pituitary hormones may recover; however, secondary adrenal insufficiency is usually permanent. CASE PRESENTATION: A 26-year old male with metastatic clear cell renal cell carcinoma was started on treatment with the anti-programmed cell death-1 monoclonal antibody (anti-PD-1 mAb) nivolumab, followed by combined nivolumab and the anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) mAb, ipilimumab. After starting nivolumab monotherapy the patient developed thyroiditis, which resolved without treatment. Prior to commencing combined ICI therapy, a random serum cortisol drawn at 1:30 pm and was 15.0 µg/dL (414 nmol/L). Three weeks after starting combined ICI therapy he developed sudden onset of severe fatigue and 1 pm serum cortisol was 2.0 µg/dL (55.2 nmol/L), adrenocorticotropic hormone (ACTH) was 16 pg/mL (3.52 pmol/L). A diagnosis of hypophysitis was made, and he was immediately started on prednisone 1 mg/kg. His symptoms resolved rapidly, and he continued immune checkpoint inhibitor therapy. He was noted to also have low gonadotropic hormones and testosterone (nadir testosterone 81.19 ng/dL). The prednisone was tapered slowly over the next six weeks to a maintenance dose of 5 mg daily. Four months after the initial presentation his cortisol remained low, but his testosterone level had increased to 973.43 ng/dL. After five months his random serum cortisol (1 pm) increased to 11.0 µg/dL (303.6 nmol/L). The prednisone was cautiously discontinued with close monitoring. Two months off glucocorticoid replacement he remained asymptomatic with an ACTH of 24.1 pg/mL (5.3 pmol/L), and cortisol of 13.0 µg/dL (358.8 nmol/L). CONCLUSIONS: This case documents the unusual recovery from secondary adrenal insufficiency in a patient who developed hypophysitis from immune checkpoint inhibitor therapy. Repeated pituitary hormone testing every three months for the first year after the development of hypophysitis may identify more patients with hypothalamic-pituitary-adrenal axis recovery.

Antibodies Against Specific MUC16 Glycosylation Sites Inhibit Ovarian Cancer Growth.

Expression of the retained C-terminal extracellular portion of the ovarian cancer glycoprotein MUC16 induces transformation and tumor growth. However, the mechanisms of MUC16 oncogenesis related to glycosylation are not clearly defined. We establish that MUC16 oncogenic effects are mediated through MGAT5-dependent N-glycosylation of two specific asparagine sites within its 58 amino acid ectodomain. Oncogenic signaling from the C-terminal portion of MUC16 requires the presence of Galectin-3 and growth factor receptors colocalized on lipid rafts. These effects are blocked upon loss of either Galectin-3 expression or activity MGAT5. Using synthetic MUC16 glycopeptides, we developed novel N-glycosylation site directed monoclonal antibodies that block Galectin-3-mediated MUC16 interactions with cell surface signaling molecules. These antibodies inhibit invasion of ovarian cancer cells, directly blocking the in vivo growth of MUC16-bearing ovarian cancer xenografts, elucidating new therapeutic modalities.

Expression of the Carboxy-Terminal Portion of MUC16/CA125 Induces Transformation and Tumor Invasion.

The CA125 antigen is found in the serum of many patients with serous ovarian cancer and has been widely used as a disease marker. CA125 has been shown to be an independent factor for clinical outcome in this disease. In The Cancer Genome Atlas ovarian cancer project, MUC16 expression levels are frequently increased, and the highest levels of MUC16 expression are linked to a significantly worse survival. To examine the biologic effect of the proximal portion of MUC16/CA125, NIH/3T3 (3T3) fibroblast cell lines were stably transfected with the carboxy elements of MUC16. As few as 114 amino acids from the carboxy-terminal portion of MUC16 were sufficient to increase soft agar growth, promote matrigel invasion, and increase the rate of tumor growth in athymic nude mice. Transformation with carboxy elements of MUC16 was associated with activation of the AKT and ERK pathways. MUC16 transformation was associated with up-regulation of a number of metastases and invasion gene transcripts, including IL-1ß, MMP2, and MMP9. All observed oncogenic changes were exclusively dependent on the extracellular "ectodomain" of MUC16. The biologic impact of MUC16 was also explored through the creation of a transgenic mouse model expressing 354 amino acids of the carboxy-terminal portion of MUC16 (MUC16c354). Under a CMV, early enhancer plus chicken ß actin promoter (CAG) MUC16c354 was well expressed in many organs, including the brain, colon, heart, kidney, liver, lung, ovary, and spleen. MUC16c354 transgenic animals appear to be viable, fertile, and have a normal lifespan. However, when crossed with p53-deficient mice, the MUC16c354:p53+/- progeny displayed a higher frequency of spontaneous tumor development compared to p53+/- mice alone. We conclude that the carboxy-terminal portion of the MUC16/CA125 protein is oncogenic in NIH/3T3 cells, increases invasive tumor properties, activates the AKT and ERK pathways, and contributes to the biologic properties of ovarian cancer.