Role of body mass index in outcomes of patients hospitalized with COVID-19 illness.

Background: Since the start of coronavirus disease 2019 (COVID-19) pandemic, several studies have linked obesity with severity of illness as well as mortality in patients with COVID-19. Outcomes of patients with overweight or obesity, who develop critical illness, have been studied extensively over the past decade where the studies have shown conflicting results. In this study, we aimed to assess the association between the body mass index (BMI) classes and outcomes among hospitalized patients with COVID-19. Methods: This was a retrospective chart review of all adults admitted to our hospital with COVID-19 illness between 1 March 2020 and 30 June 2020. Patients were divided into four groups based on their BMI range as follows: patients with underweight (BMI < 18.5 kg/m2), patients with normal weight (BMI 18.5-24.9 kg/m2), patients with overweight (BMI 25-29.9 kg/m2), and patients with obesity (BMI ≥ 30 kg/m2). Results: 1274 patients were admitted during the study period. There were 24 (1.9%) patients with underweight, 268 (21%) patients with normal weight, 445 (34.9%) patients with overweight, and 537 (42.2%) patients with obesity. Patients with obesity were younger (p < 0.001) and there were more females among patients with underweight and patients with obesity (54% and 48% respectively, p < 0.001). There were no differences in subgroup with regards to presence of hypertension, diabetes mellitus, coronary artery disease, congestive heart failure, and dyslipidemia. In a multivariate logistic regression model, patients with overweight and patients with obesity had higher odds of requiring mechanical ventilation. BMI class was not associated with difference in survival time in a multivariate analysis. Conclusions: In our large single-center study of hospitalized patients with COVID-19, patients with overweight and obesity had higher need for mechanical ventilation but had similar mortality when compared to patients with normal weight and underweight.

Hypercalcemia and Renal Mass: A Diagnostically Challenging Case.

Hypercalcemia of malignancy frequently occurs in patients with solid tumors as a paraneoplastic syndrome known as humoral hypercalcemia of malignancy (HHM), caused by the secretion of parathyroid hormone-related peptide (PTHrP). On the other hand, 1,25-dihydroxyvitamin D [1,25(OH)2D]-mediated hypercalcemia is a less common cause of hypercalcemia of malignancy and is mostly observed in lymphoma patients. Here, we report an interesting case of a 77-year-old male nursing home resident with suspected renal cell carcinoma (RCC) presenting with severe hypercalcemia (18.7 mg/dL), which was initially presumed to be HHM. However, workup revealed nonsuppressed parathyroid hormone, low PTHrP, and elevated 25-hydroxyvitamin D and 1,25(OH)2D levels. Steroids were initiated due to an inadequate response to bisphosphonate therapy and elevated vitamin D metabolites, resulting in further reduction in serum calcium levels. This case highlights the need to consider multiple concurrent etiologies in the differential diagnosis of severe hypercalcemia, including the possible role of calcitriol-mediated hypercalcemia in RCC.

Impact of Prediabetes and Type-2 Diabetes on Outcomes in Patients with COVID-19.

INTRODUCTION: The true impact of prediabetes and type-2 diabetes in patients with COVID-19 remains unknown, with studies thus far providing conflicting evidence. METHODS: This is a single-center retrospective observational study involving 843 hospitalized patients with SARS-CoV-2 infection. Primary outcomes, mortality, and mechanical ventilation use were compared among the three groups: control, prediabetes, and type-2 diabetes. Binomial regression analysis was used to determine predictors of mortality and mechanical ventilation requirement. RESULTS: Age was a significant predictor of mortality. On stratifying our patients based on their age, older patients aged 55 years and above had no difference in mortality or mechanical ventilation requirement among the three groups of control, prediabetes, and type-2 diabetes. However, among the younger population aged less than 55 years, patients with type-2 diabetes had significantly higher mortality as compared with patients in control and prediabetes groups (27% vs 12.5% vs 9%, p 0.025). Additionally, newly diagnosed type-2 diabetes patients demonstrated lower mortality rate in comparison to previously known type-2 diabetes patients (18% vs 40%, p 0.005). Outcomes in the prediabetes group were similar to that in the control group. Admission hyperglycemia was associated with higher mortality regardless of diabetes status. CONCLUSION: In older patients aged 55 years and above, status of type-2 diabetes does not influence their mortality. However, in younger patients aged less than 55 years, the presence of type-2 diabetes is an important driver of mortality. Newly diagnosed type-2 diabetes, in comparison with previously diagnosed type-2 diabetes, may have better survival. Presence of prediabetes did not affect outcomes in patients with COVID-19 infection.

Drugs and hyperglycemia: A practical guide.

Drug-induced diabetes is one of the factors contributing to the increasing incidence of diabetes worldwide. This review considers the frequency, pathogenesis and treatment of drug-induced diabetes. Drugs that induce diabetes include hormonal therapy, especially glucocorticoids and androgen blockers, cardiovascular drugs, especially statins, beta-blockers and diuretics, antipsychotics, especially clozapine, olanzapine and quetiapine, antiretrovirals (protease inhibitors and non-reverse transcriptase inhibitors - NRTIs) and other drugs (mechanistic target of rapamycin inhibitors -mTORs, post organ transplantation drugs, tyrosine kinase inhibitors and interferon-alpha). Abnormalities of the distal gluco-regulatory pathways of hyperglycemia involve decreased insulin secretion and frequent insulin resistance, whereas the proximal defects are unknown, thus limiting targeted treatment. Drug-induced diabetes is potentially reversible and the risk is underestimated. There is little information on its long-term effects on microvascular complications as clinical trials have not been long enough and neither have they focused on these factors. Overall management includes awareness of a drug's diabetogenic potential, underlying diabetes risk, benefits and risks of continuing vs discontinuing the drug, plus a consideration of drug duration and dose. While diabetes and its severity can be identified and controlled, the likelihood of future diabetes complications frequently cannot. This, balanced against the predicted benefit of the drug, results in clinical uncertainty. Empirical approaches to drug-related hyperglycemia include decreasing the dose or selecting an alternative treatment, if possible. In the absence of drug-specific evidence, treatment of drug-induced hyperglycemia and diabetes is similar to comprehensive standard diabetes care, including lifestyle modifications, oral/injectable antidiabetic agents and insulin. Important clinical considerations include surveillance of glucose before and during treatment and, in some cases, institution of diabetes preventive measures like lifestyle modification and early treatment. Future research is needed to elucidate pathophysiology and optimal targeted treatment for drug-induced diabetes and its long-term complications.

Does Nursery-Based Intensified Anticipatory Guidance Reduce Emergency Department Use for Nonurgent Conditions in the First Month of Life? A Randomized Controlled Trial.

Objective. We aimed to evaluate the impact of an intensified anticipatory guidance program in the nursery on Emergency Department (ED) use for nonurgent conditions (NUCs) in the neonatal period. Methods. Parturient mothers of healthy newborns were randomized to an intervention group or control group. Baseline and 1-month follow-up knowledge surveys regarding newborn care were conducted. The primary outcome was the proportion of neonates who used the ED for a NUC. Secondary outcome was change in caregivers' knowledge on NUC. Results. Of a total of 594 mothers, 323 (54%) agreed to participate and were randomized to intervention (n = 170) or control (n = 153) group. Most were Hispanic (68%), single (61%), primiparous (39%), and without high school diploma (44%). 35 (21%) neonates in the intervention group and 41 (27%) in the control group were brought at least once for a NUC to the ED (p = 0.12). There was no statistically significant difference in within subject change on knowledge scores between the two study arms. Conclusions. Neonatal ED visits for NUCs occur frequently. This nursery-based intensified anticipatory guidance program had no statistically significant impact on neonatal ED use for NUC, nor on neonatal care-relevant knowledge among parturient mothers. Alternative modalities and timing of parental educational intervention may need to be considered. This trial is registered with Clinical Trials Number NCT01859065 (Clinicaltrials.gov).

Diabetes insipidus: celebrating a century of vasopressin therapy.

Diabetes mellitus, widely known to the ancients for polyuria and glycosuria, budded off diabetes insipidus (DI) about 200 years ago, based on the glucose-free polyuria that characterized a subset of patients. In the late 19th century, clinicians identified the posterior pituitary as the site of pathology, and pharmacologists found multiple bioactivities there. Early in the 20th century, the amelioration of the polyuria with extracts of the posterior pituitary inaugurated a new era in therapy and advanced the hypothesis that DI was due to a hormone deficiency. Decades later, a subset of patients with polyuria unresponsive to therapy were recognized, leading to the distinction between central DI and nephrogenic DI, an early example of a hormone-resistant condition. Recognition that the posterior pituitary had 2 hormones was followed by du Vigneaud's Nobel Prize winning isolation, sequencing, and chemical synthesis of oxytocin and vasopressin. The pure hormones accelerated the development of bioassays and immunoassays that confirmed the hormone deficiency in vasopressin-sensitive DI and abundant levels of hormone in patients with the nephrogenic disorder. With both forms of the disease, acquired and inborn defects were recognized. Emerging concepts of receptors and of genetic analysis led to the recognition of patients with mutations in the genes for 1) arginine vasopressin (AVP), 2) the AVP receptor 2 (AVPR2), and 3) the aquaporin 2 water channel (AQP2). We recount here the multiple skeins of clinical and laboratory research that intersected frequently over the centuries since the first recognition of DI.

Tumors, IGF-2, and hypoglycemia: insights from the clinic, the laboratory, and the historical archive.

Tumors of mesenchymal and epithelial origin produce IGF-2, which activates pathways in the tumors. In a minority of patients, the tumors (hepatomas, fibromas, and fibrosarcomas are the most common among many) release into the circulation enough IGF-2-related peptides to mimic the fasting hypoglycemia characteristic of patients with insulin-producing islet-cell tumors. Rarely, markedly elevated IGF-2 levels produce somatic changes suggestive of acromegaly. Typically, the elevated IGF-2 levels are associated with suppressed plasma levels of insulin, IGF-1, and GH. Complicating the pathophysiology are the IGF binding proteins (IGFBPs) that can bind IGF-2 and IGF-1, modifying hormone metabolism and action. IGFBP concentrations are often altered in the presence of these tumors. At the cellular level, the 3 hormone-related ligands, IGF-2, IGF-1, and insulin, all bind to 4 (or more) types of IGF-1 receptor (IGF-1R) and insulin receptor (IR). Each receptor has its own characteristic affinity for each ligand, a tyrosine kinase, and overlapping profiles of action in the target cells. The IGF-2R, in addition to binding mannose-6-phosphate-containing proteins, provides an IGF-2 degradation pathway. Recent evidence suggests IGF-2R involvement also in signal transduction. Surgery, the treatment of choice, can produce a cure. For patients not cured by surgery, multiple therapies exist, for the tumor and for hypoglycemia. Potential future therapeutic approaches are sketched. From 1910 to 1930, hypoglycemia, insulin, insulinomas, and non-islet-cell tumors were recognized. The latter third of the century witnessed the emergence of the immunoassay for insulin; the IGFs, their binding proteins, and assays to measure them; and receptors for the insulin-related peptides as well as the intracellular pathways beyond the receptor. In closing, we replace non-islet-cell tumor hypoglycemia, an outdated and misleading label, with IGF-2-oma, self-explanatory and consistent with names of other hormone-secreting tumors.