Impact of diabetes on COVID-19 patient health outcomes in a vulnerable racial minority community.

BACKGROUND: Diabetes is a growing health concern in the United States and especially New York City. New York City subsequently became an epicenter for the coronavirus pandemic in the Spring of 2020. Previous studies suggest that diabetes is a risk factor for adverse outcomes in COVID-19. OBJECTIVE: To investigate the association between diabetes and COVID-19 outcomes as well as assess other covariates that may impact health outcomes. DESIGN: Retrospective cohort study of COVID-19 hospitalized patients from March to May, 2020. PARTICIPANTS: In total, 1805 patients were tested for COVID-19 and 778 tested positive for COVID-19. Patients were categorized into 2 groups: diabetes (measured by an Hba1c >6.5 or had a history of diabetes) and those without diabetes. RESULTS: After controlling for other comorbidities, diabetes was associated with increased risk of mortality (aRR = 1.28, 95% CI 1.03-1.57, p = 0.0231) and discharge to tertiary care centers (aRR = 1.69, 95% CI 1.04-2.77, p = 0.036). compared to non-diabetes. Age and coronary artery disease (CAD) increased the risk of mortality among diabetic patients compared to patients with diabetes alone without CAD or advanced age. The diabetes cohort had more patients with resolving acute respiratory failure (62.2%), acute kidney injury secondary to COVID-19 (49.0%) and sepsis secondary to COVID-19 (30.1%). CONCLUSION: This investigation found that COVID-19 patients with diabetes had increased mortality, multiple complications at discharge, and increased rates of admission to a tertiary care center than those without diabetes suggesting a more severe and complicated disease course that required additional services at time of discharge.

Syndrome of inappropriate antidiuretic hormone in a patient with leptomeningeal carcinomatosis.

BACKGROUND: Leptomeningeal carcinomatosis is a condition in which metastatic cancer cells infiltrate the meninges of the brain and spinal cord, progressing to also involve the cerebrospinal fluid. Incidence of leptomeningeal carcinomatosis arising from an esophageal cancer is particularly rare. CASE PRESENTATION: Here, we present a case report of a 76-year-old Caucasian man with a history of esophageal adenocarcinoma status-post chemoradiation followed by resection. He was admitted to our unit for intractable headache, nausea without emesis, anorexia, weakness, gait instability, delirium, syncope, and near syncope. Our diagnostic workup revealed leptomeningeal carcinomatosis and syndrome of inappropriate antidiuretic hormone. Our patient was treated with lumbar puncture for the headache, methotrexate for the leptomeningeal carcinomatosis, and table salt for the syndrome of inappropriate antidiuretic hormone. Despite our best efforts, our patient died 6 weeks posttreatment. CONCLUSIONS: Understanding the molecular pathogenesis of the development of syndrome of inappropriate antidiuretic hormone associated with leptomeningeal carcinomatosis from metastatic esophageal adenocarcinoma would help us to identify patients at risk and treat them accordingly.

The effects of COX-1 and COX-2 inhibitors on prostaglandin synthesis and the formation of heterotopic bone in a rat model.

INTRODUCTION: Traumatic heterotopic ossification (HO) is a common clinical condition associated with various orthopedic procedures that involve injury to soft tissues near bone. In this study, we tested the hypothesis that the prophylactic effects of NSAID's in the treatment of HO are mediated via inhibition of the COX-2 enzyme. Here we describe a rat model that simulates HO in the human that was used to test the above hypothesis. MATERIALS AND METHODS: Heterotopic ossification was surgically induced in the quadriceps by injury to the muscle and femoral periosteum and transplantation of donor bone marrow cells containing osteoprogenitors into the site of injury. HO was imaged and quantified by micro-CT scanning of femurs removed from sacrificed animals at 6 weeks post-injury, three-dimensional computer reconstructions of the scanned bones and computer-assisted morphometric analysis. Prostaglandin E(2) (PGE(2)) synthesis was quantified using an enzyme immunoassay system. The effects of a nonselective COX inhibitor or specific inhibitors of COX-1 or COX-2 following oral administration on the content of ectopic bone and PGE(2) were also measured. RESULTS: Micro-CT and histological analyses demonstrated that all of the femurs in operated limbs developed HO in the vastus lateralis muscle belly of the quadriceps close to the anterior femur. Only the COX-1,2 nonselective and COX-2 inhibitors significantly decreased HO formation (by about one-third in each case; P < 0.05). PGE(2) synthesis at the site of injury was increased 50- and 100-fold (to 25 ng/g tissue) within 1 and 7 days, respectively, post-injury with the levels declining to near baseline within 2 weeks of surgery. Both the COX-1,2 nonselective and COX-2 inhibitors significantly decreased PGE(2) levels to 25% of control HO levels within 24 h of the first administration, even at low dosages. The COX-1 inhibitor only produced the same effect after 1 week of administration. CONCLUSION: These findings suggest that although inhibitors of COX-2 or COX-1 reduced PGE(2) synthesis, only the COX-2 enzyme plays a role in the mechanism of traumatic HO.

Astrocyte differentiation selectively upregulates CCL2/monocyte chemoattractant protein-1 in cultured human brain-derived progenitor cells.

Chemokines (chemoattractant cytokines) and their receptors are present in the brain and may play roles in both neurodevelopment and neuropathology. Increased brain levels of monocyte chemoattractant protein-1 (MCP-1), also known as CCL2, are found in patients with human immunodeficiency virus type 1 (HIV-1)-associated dementia and other acute and chronic neurologic diseases. Although the function of CCL2 in the brain is unclear, it is believed that upregulation of this chemokine during neuropathologic or neuroinflammatory conditions leads to recruitment of activated monocytes into the brain, where they differentiate into macrophages producing neurotoxic and inflammatory molecules. We recently showed that human fetal brain-derived progenitor cells are susceptible to HIV-1 and JC virus infection, and that differentiation toward an astrocyte phenotype increased virus production from these cells. In the current study, we found that in the absence of infection, progenitors produced moderate levels of CCL2 (5.6 ng per million cells). Astrocyte differentiation over 3 weeks increased CCL2 protein levels 30-fold in a biphasic manner, whereas neuronal differentiation decreased production 20-fold. Electromobility shift assays (EMSAs) demonstrated increased nuclear NF-kappaB levels within 2 h of initiating astrocyte differentiation, and inhibitors of NF-kappaB activation partially blocked the CCL2 increase in differentiating astrocytes. Transfection of progenitors with mutated CCL2 promoter/CAT reporter constructs showed that the distal promoter region, containing NF-kappaB and NF-I binding sites, is important for differentiation-induced CCL2 upregulation. Together these results suggest that the transcription factor NF-kappaB, and possibly NF-I, contribute to the upregulation of CCL2 chemokine production during the differentiation of human progenitor cells toward an astrocyte phenotype.