CONTEXT:Diabetes or hyperglycemia at admission are established risk factors for adverse outcomes during hospitalization for COVID-19, but the impact of prior glycemic control is not clear.OBJECTIVE:We aimed to examine the associations between admission variables, including glycemic gap, and adverse clinical outcomes in patients hospitalized with COVID-19 infection.METHODS:We examined the relationship between clinical predictors, including acute and chronic glycemia, and clinical outcomes, including intensive care unit (ICU) admission, mechanical ventilation (MV), and mortality among 1786 individuals with diabetes or hyperglycemia (glucose > 10 mmol/L twice in 24 hours) who were admitted from March 2020 through February 2021 with COVID-19 infection at 5 university hospitals in the eastern United States.RESULTS:The cohort was 51.3% male, 53.3% White, 18.8% Black, 29.0% Hispanic, with age = 65.6 ± 14.4 years, BMI = 31.5 ± 7.9 kg/m2, glucose = 12.0 ± 7.5 mmol/L [216 ± 135 mg/dL], and HbA1c = 8.07% ± 2.25%. During hospitalization, 38.9% were admitted to the ICU, 22.9% received MV, and 10.6% died. Age (P < 0.001) and admission glucose (P = 0.014) but not HbA1c were associated with increased risk of mortality. Glycemic gap, defined as admission glucose minus estimated average glucose based on HbA1c, was a stronger predictor of mortality than either admission glucose or HbA1c alone (OR = 1.040 [95% CI: 1.019, 1.061] per mmol/L, P < 0.001). In an adjusted multivariable model, glycemic gap, age, BMI, and diabetic ketoacidosis on admission were associated with increased mortality, while higher estimated glomerular filtration rate (eGFR) and use of any diabetes medication were associated with lower mortality (P < 0.001).CONCLUSION:Relative hyperglycemia, as measured by the admission glycemic gap, is an important marker of mortality risk in COVID-19.

Poor socioeconomic status and inadequate insurance coverage may affect an individual’s ability to utilize healthcare services. This study was conducted to evaluate whether the type of insurance coverage is associated with missed appointments for diabetes care. Data analysis included all patients with diabetes mellitus (DM) managed at a major academic center between Jan 2015 and Dec 2020. Association between insurance coverage and proportion of missed appointments was evaluated using analysis of covariance with adjustments for demographic variables and social determinants of health. The relationship between proportion of missed appointments and glycemic control was also evaluated in multivariate analyses. The final dataset included 30,633 patients, out of which 14,064 (46%) reported commercial insurance, 13,376 (44%) reported Medicare and 3,193 (10%) reported Medicaid coverage. Medicaid group was identified to have the highest proportion of Spanish-speakers, African Americans, women, current smokers and single individuals. Proportion of missed appointments was 18.1 ± 18.1% in Medicaid covered patients as compared to 12.1 ± 15.3% among commercially insured and 10.2 ± 14.1% among Medicare covered patients (p <0.001) . Type of insurance was found to be a statistically significant predictor of the proportion of missed appointments after adjusting for age, race, preferred language, marital status, smoking, BMI, HbA1c and type of diabetes (p<0.001) . Proportion of missed appointments was associated with HbA1c with partial correlation coefficient +0.1 (p <0.001) after adjusting for age, race, gender, type of insurance, BMI and type of diabetes. We conclude that Medicaid covered patients with diabetes have higher proportion of missed clinic appointments and higher HbA1C. More research is needed to evaluate the root causes of inability to keep appointments in this population so that strategies for improved healthcare delivery can be designed. Disclosure R.Radhakrishnan: None. W.H.Cade: None. E.Bernal-mizrachi: None. R.Garg: None.

While diabetes and admission blood glucose (BG) are established risk factors for adverse outcomes during hospitalization for COVID-19, reports on the impact of prior glycemic control have been variable. We examined the relationship between acute and chronic glycemia on risk of ICU admission, mechanical ventilation (MV) , and mortality among 1,786 patients with diabetes or hyperglycemia (BG > 180 mg/dl twice during any 24-hr period during hospitalization) admitted from March 2020 to February 2021 with COVID-at 5 large university hospitals in the eastern U.S. The cohort was 51.3% male, 53.3% White, 18.8% Black, 29.3% Hispanic, with age = 64.8 ± 13.8 y, BMI = 31.5 ± 7.9 kg/m2, admission BG = 216 ± 134 mg/dl, and HbA1c = 8.1 ± 2.2%. During hospitalization, 38.9% were admitted to the ICU, 22.9% received MV, and 10.6% died. In multivariate regression analysis, among demographic factors, age was the strongest risk factor for in-hospital mortality (OR = 1.per year [95% CI: 1.04, 1.06]) , and Hispanic ethnicity was the greatest risk factor for ICU admission (OR = 1.45 [95% CI: 1.16, 1.80]) and intubation (OR = 1.64 [95% CI: 1.28, 2.10]) . Higher BMI (p = 0.005) and admission BG (p = 0.014) were associated with increased risk of mortality, but HbA1c was not. The glycemic gap (GG) , defined as admission BG minus estimated average BG based on HbA1c, was a stronger predictor of mortality than either admission BG or HbA1c alone. Mortality rate was 5.7% for GG < -20 mg/dl; 12.2% for GG = -20 to < 20 mg/dl; 12.4% for GG = 20 to < 100 mg/dl; and 16.1% for GG ≥ 100 mg/dl (p for trend < 0.001) . Conclusion: Among patients with diabetes or hyperglycemia admitted for COVID-19, in addition to previously established risk factors for poor outcomes (age, Hispanic ethnicity, and BMI) , we found that GG is a stronger predictor of in-hospital mortality than blood glucose alone. This suggests that relative hyperglycemia, as measured by the admission GG, is an important marker of disease severity in COVID-and potentially other serious illnesses. Disclosure M.E.Mcdonnell: Advisory Panel; Everlywell, Inc., Research Support; Lilly, Stock/Shareholder; Abbott Diabetes. G.P.Westcott: None. D.C.Simonson: Stock/Shareholder; GI Windows, Phase V Technologies, Inc. G.Gopalakrishnan: Research Support; Eli Lilly and Company, Spruce Biosciences. R.Garg: None. J.Mitri: Consultant; dairy management, Lnutra. R.S.Weinstock: Research Support; Boehringer Ingelheim International GmbH, Dexcom, Inc., Diasome, Eli Lilly and Company, Insulet Corporation, Kowa Pharmaceuticals America, Inc., Medtronic, Novo Nordisk, Tandem Diabetes Care, Inc., Tolerion, Inc. M.Greenfield: None. N.E.Palermo: Research Support; Dexcom, Inc. R.Radhakrishnan: None. Funding Brigham-TechFoundation, Cambridge, MA 2021

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•Frequency of missed clinic appointments is associated with high HbA1c level.•Patients with diabetes who have Medicaid coverage have higher chances of missing a clinic appointment for diabetes.•The same group of patients also have high HbA1c.•Further studies need to explore the specific reasons for underutilization of health care services by Medicaid covered population.

Introduction: Renal dysfunction commonly occurs in patients with cirrhosis and is typically associated with poor prognosis. Several pathophysiologic mechanisms are responsible for renal disease in these patients, prompt identification permits individualized management.Areas covered: Pathophysiology, evaluation and differential diagnosis, management and prognosis of renal disease in patients with cirrhosis. Special focus on management of hepatorenal syndrome and indications for simultaneous liver-kidney transplantation.Literature search methodology: a detailed literature search was performed using PubMed without date restrictions. Published guidelines and position papers were also used and cross-referenced to identify additional studies.Expert opinion: The prognostic significance of renal dysfunction in patients with cirrhosis is highlighted by the inclusion of serum creatinine in the model for end-stage liver disease (MELD). Both acute and chronic renal dysfunction result in increased mortality in patients with cirrhosis, although there are marked differences related to the etiology of renal disease. Early recognition and prompt intervention determined by the most likely etiology are key in the management of these patients. Simultaneous liver-kidney transplantation improves patient survival compared to isolated liver transplantation in patients with cirrhosis and persistent renal impairment; however, selection of candidates must be judicious and individualized due to the ongoing shortage of donor kidneys.

Abstract Introduction While research suggests that asylum-seekers often present with a high level of medical and psychological needs, there is a dearth of research exploring sleep quality in this population, and, accordingly, the role that the sleep medicine community may be able to play in alleviating the suffering of this population. Therefore, this study aims to assess the prevalence of sleep disruption amongst asylum-seekers presenting to a South Florida clinic and to categorize these disruptions according to severity and type. Methods This is a cross-sectional study utilizing medical affidavits for asylum seekers in South Florida from 2018-2020 (n=54). Affidavits were reviewed for narrative descriptions of sleep quality and information from validated screeners regarding sleep; demographic information was also collected. Affidavits were excluded if they did not include itemized answers to screening questions. Results Out of 54 asylum-seekers (31% male, median age=34.5 years), 72.2% reported sleep disturbance. 38.9% reported nightmares, 66.7% reported insomnia of any type, and 29.6% reported severe insomnia. Asylum-seekers that screened positive for post-traumatic stress disorder (PTSD) were more likely to report ongoing sleep disturbance than asylum-seekers that screened negative for PTSD (p=.004). Sleep disturbance prevalence did not vary significantly by gender identity or country of origin. Conclusion This study reveals a high prevalence of sleep disruption amongst asylum-seekers in South Florida. The asylum-seekers in our study were more likely to experience insomnia than nightmares, but many experienced both; sleep disturbance was significantly associated with screening positive for PTSD. Our findings suggest that physicians working with asylum-seekers should ask about sleep quality and offer appropriate care. Directions for further research include investigating how poor sleep quality impacts the health and wellbeing of asylum-seekers. Support (if any) None

People with diabetes (DM) hospitalized with COVID-19 infection have a 2-3 fold higher risk of death compared with those without DM, and mechanical ventilation (MV) has been identified as a major risk factor for death. While stress hyperglycemia (StH) has been established as a risk factor for death in some critically ill cohorts, it is not a well-established risk factor for MV in COVID-19. The COVIDEastDM consortium pooled data from 5 academic hospitals on the East Coast of the US to study the relationship between hyperglycemia and COVID-19 outcomes. Data were obtained retrospectively from electronic records of adults with COVID-19 and either DM or StH (defined in this cohort as day-1 admission blood glucose >180 mg/dl and A1c <6.5%). This analysis included 3,435 individuals, of which 1,001 (29.1%) required MV and 748 (21.8%) died. The mean age was 67 ± 15 yrs., BMI 30.4 ± 7.7 kg/m2, A1c 7.98 ± 2.21 % and glucose 184 ± 104 mg/dl. Additionally, 57% were male, 4 % Asian,19% Black, 52% White, and 28% Hispanic. In a univariate analysis, risk factors for MV included younger age (OR 0.98 [95% CI 0.97, 0.99] per year older), male sex (OR 1.4 [1.2, 1.7]), BMI (OR 1.013 [1.003, 1.023] per kg/m2), Hispanic ethnicity (OR 1.16 [1.07, 1.28]) and the presence of diabetic ketoacidosis (n=38) at admission (OR 3.9 [2.0, 7.5]). Patients with StH were more likely to require MV (OR 1.93, [1.10, 3.39]). In a multivariate analysis, this relationship was continuous, with both lower A1c and higher glucose increasing risk of MV (p< 0.01 for higher glucose, p<0.001 for lower A1c). Patients who required MV were more likely to die than those who did not require MV (OR 5.1, [4.3, 6.1]) and StH predicted mortality in the multivariate analysis. Thus, in patients hospitalized with COVID19 infection, StH is a strong predictor of both MV and death in COVID-19 infected adults. While it is unclear if StH is a cause or effect of severe COVID-19, its presence early in the hospital course identifies higher risk patients and could potentially impact management. Disclosure M. E. Mcdonnell: Stock/Shareholder; Spouse/Partner; Abbott Diabetes. N. E. Palermo: None. R. Radhakrishnan: None. G. P. Westcott: None. R. S. Weinstock: Research Support; Self; Boehringer Ingelheim International GmbH, Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Insulet Corporation, Kowa Research Institute, Inc., Medtronic, Tolerion, Inc. R. Garg: None. D. C. Simonson: Stock/Shareholder; Spouse/Partner; Phase V Technologies, Inc. G. Cromwell: None. G. Gopalakrishnan: None. M. Greenfield: None. M. Johnson: None. S. R. Katta: None. J. Lebastchi: None. J. Mitri: Consultant; Self; L-Nutra. Funding TechFoundation; Brigham Education Institute

Many inflammation-associated diseases, including cancers, increase in women after menopause and with obesity. In contrast to anti-inflammatory actions of 17β-estradiol, we find estrone, which dominates after menopause, is pro-inflammatory. In human mammary adipocytes, cytokine expression increases with obesity, menopause, and cancer. Adipocyte:cancer cell interaction stimulates estrone- and NFκB-dependent pro-inflammatory cytokine upregulation. Estrone- and 17β-estradiol-driven transcriptomes differ. Estrone:ERα stimulates NFκB-mediated cytokine gene induction; 17β-estradiol opposes this. In obese mice, estrone increases and 17β-estradiol relieves inflammation. Estrone drives more rapid ER+ breast cancer growth in vivo. HSD17B14, which converts 17β-estradiol to estrone, associates with poor ER+ breast cancer outcome. Estrone and HSD17B14 upregulate inflammation, ALDH1 activity, and tumorspheres, while 17β-estradiol and HSD17B14 knockdown oppose these. Finally, a high intratumor estrone:17β-estradiol ratio increases tumor-initiating stem cells and ER+ cancer growth in vivo. These findings help explain why postmenopausal ER+ breast cancer increases with obesity, and offer new strategies for prevention and therapy.

Neoplasms in the heart are exceptionally rare. Cardiac sarcomas are the most common malignant type. Clinical presentations can vary from congestive heart failure, to thromboembolism and arrhythmias. A 76-year-old male with history of severe mitral regurgitation status post mitral valve annuloplasty