A randomized pilot study using calcitriol in hospitalized COVID-19 patients.

The systemic illness associated with SARS-CoV-2 infection results in hospitalization rate of 380.3 hospitalizations per 100,000 population, overwhelming health care systems. Vitamin D regulates expression of approximately 11,000 genes spanning many physiologic functions that include regulation of both innate and adaptive immune function. We investigate potential benefit of calcitriol therapy given to patients hospitalized with COVID-19. This was an open label, randomized clinical trial of calcitriol or no treatment given to hospitalized adult patients with COVID-19. Subjects were randomly assigned treatment with calcitriol 0.5 µg daily for 14 days or hospital discharge; or no treatment (1:1) at time of enrollment. We enrolled 50 consecutive patients, 25 per trial arm. The change in peripheral arterial oxygen saturation to the inspired fraction of oxygen (SaO2/FIO2 ratio) was calculated on admission and discharge between the groups. The control group had an average increase of +13.2 (±127.7) on discharge and the calcitriol group had an increase of +91.04 (±119.08) (p = .0305), suggesting an improvement in oxygenation among subjects who received calcitriol. Additionally, 12 patients in the control group required oxygen supplementation on admission and 21 of them were discharged on room air. 14 subjects needed oxygen supplementation in the calcitriol group on admission while all 25 were discharged on room air. Other clinical markers showed the average length of stay was 9.24 (±9.4) in the control group compared to 5.5 (±3.9) days in the calcitriol group (p = .14). The need for ICU transfer was 8 in the control group and 5 in the calcitriol group. There were 3 deaths and 4 readmissions in the control group and 0 deaths and 2 readmissions in the calcitriol group. This pilot study illustrates improvement in oxygenation among hospitalized patients with COVID-19 treated with calcitriol and suggests the need for a larger randomized trial.

BROWN TUMORS SECONDARY TO PARATHYROID CARCINOMA MASQUERADING AS SKELETAL METASTASES ON 18F-FDG PET/CT: A CASE REPORT.

OBJECTIVE: Brown tumors develop as skeletal manifestations of hyperparathyroidism. Increased osteoclast activity leads to accumulation of highly active giant cells and to excess cortical bone resorption, producing fibrous cysts. Though most often reported in patients with parathyroid adenomas, brown tumors secondary to parathyroid carcinoma create a clinical dilemma. Increased signal uptake on 2-deoxy-2-(fluorine-18)fluoro-D-glucose positron emission tomography (18F-FDG PET)/computed tomography (CT) seen within brown tumors may be indistinguishable from bone metastases. We report a case of parathyroid carcinoma in a 38-year-old man presenting with osteolytic bone lesions on 18F-FDG PET/CT that were diagnosed as brown tumors by biopsy. METHODS: We describe the patient history, presentation, diagnostic studies, and treatment. RESULTS: We report a case of a 38-year-old man diagnosed with parathyroid carcinoma with associated hypercalcemia and elevated parathyroid hormone levels who had undergone 3 surgical resections for local recurrences and had persistent hypercalcemia. He was found to have multiple osteolytic lesions throughout his skeleton on 18F-FDG PET/CT imaging 2 months after diagnosis. Biopsy of a right scapula lesion confirmed a brown tumor. CONCLUSION: The role of 18F-FDG PET/CT in management of parathyroid carcinoma has not been systematically evaluated. Skeletal manifestations of parathyroid carcinoma may be present in this imaging modality. Clinicians should consider the possibility of brown tumors in patients with parathyroid carcinoma who undergo 18F-FDG PET/CT imaging.

Long-Term Physical HRQOL Decreases After Single Lung as Compared With Double Lung Transplantation.

BACKGROUND: Single lung transplantation (SLT) and double lung transplantation (DLT) are associated with differences in morbidity and mortality, although the effects of transplant type on patient-reported outcomes are not widely reported and conclusions have differed. Previous studies compared mean health-related quality of life (HRQOL) scores but did not evaluate potentially different temporal trajectories in the context of longitudinal follow-up. To address this uncertainty, this study was designed to evaluate longitudinal HRQOL after SLT and DLT with the hypothesis that temporal trajectories differ between SLT and DLT. METHODS: Patients transplanted at a single institution were eligible to be surveyed at 1 month, 3 months, 6 months, and then annually after transplant using the Short Form 36 Health Survey, with longitudinal physical component summary (PCS) and mental component summary (MCS) scores as the primary outcomes. Multivariable mixed-effects models were used to evaluate the effects of transplant type and time posttransplant on longitudinal PCS and MCS after adjusting age, diagnosis, rejection, Lung Allocation Score quartile, and intubation duration. Time by transplant type interaction effects were used to test whether the temporal trajectories of HRQOL differ between SLT and DLT recipients. HRQOL scores were referenced to general population norms (range, 40 to 60; mean, 50 ± 10) using accepted standards for a minimally important difference (½ SD, 5 points). RESULTS: Postoperative surveys (n = 345) were analyzed for 136 patients (52% male, 23% SLT, age 52 ± 13 years, LAS 42 ± 12, follow-up 37 ± 29 months [range, 0.6 to 133]) who underwent lung transplantation between 2005 and 2016. After adjusting for model covariates, overall posttransplant PCS scores have a significant downward trajectory (p = 0.015) whereas MCS scores remain stable (p = 0.593), with both averaging within general population norms. The time by transplant type interaction effect (p = 0.002), however, indicate that posttransplant PCS scores of SLT recipients decline at a rate of 2.4 points per year over the total observation period compared to DLT. At approximately 60 months, the PCS scores of SLT recipients, but not DLT recipients, fall below general population norms. CONCLUSIONS: The trajectory of physical HRQOL in patients receiving SLT declines over time compared with DLT, indicating that, in the longer term, SLT recipients are more likely to have physical HRQOL scores that fall substantively below general population norms. Physical HRQOL after 5 years may be a consideration for lung allocation and patient counseling regarding expectations when recommending SLT or DLT.

Nutritional and Micronutrient Care of Bariatric Surgery Patients: Current Evidence Update.

PURPOSE OF REVIEW: The continued success of bariatric surgery to treat obesity and obesity-associated metabolic conditions creates a need for a strong understanding of clinical nutrition both before and after these procedures. RECENT FINDINGS: Surgically induced alteration of gastrointestinal physiology can affect the nutrition of individuals, especially among those who have undergone malabsorptive procedures. While uncommon, a subset of patients may develop protein-calorie malnutrition. In these cases, nutrition support should be tailored to the severity of malnutrition. Among all patients who undergo bariatric surgery, high rates of micronutrient deficiencies have been observed. To mitigate these deficiencies, empiric supplementation with multivitamins, calcium citrate, and vitamin D is generally recommended. Periodic surveillance should be performed for commonly deficient micronutrients, including thiamin (B1), folate (B9), cobalamin (B12), iron, and vitamin D. Following Roux-en-Y gastric bypass, serum levels of copper and zinc should also be monitored. In addition, lipid-soluble vitamins should be monitored following biliopancreatic diversion with/without duodenal switch.

Nutrition in Type 2 Diabetes and the Metabolic Syndrome.

For individuals at risk for type 2 diabetes mellitus or the metabolic syndrome, adherence to an idealized dietary pattern can drastically alter the risk and course of these chronic conditions. Target levels of carbohydrate intake should approximate 30% of consumed calories. Healthy food choices should include copious fruits, vegetables, and nuts while minimizing foods with high glycemic indices, especially processed foods.

Previous gastric bypass surgery complicating total thyroidectomy.

Hypocalcemia is a well-known complication of total thyroidectomy. Patients who have previously undergone gastric bypass surgery may be at increased risk of hypocalcemia due to gastrointestinal malabsorption, secondary hyperparathyroidism, and an underlying vitamin D deficiency. We present the case of a 58-year-old woman who underwent a total thyroidectomy for the follicular variant of papillary thyroid carcinoma. Her history included Roux-en-Y gastric bypass surgery. Following the thyroid surgery, she developed postoperative hypocalcemia that required large doses of oral calcium carbonate (7.5 g/day), oral calcitriol (up to 4 µg/day), intravenous calcium gluconate (2.0 g/day), calcium citrate (2.0 g/day), and ergocalciferol (50,000 IU/day). Her serum calcium levels remained normal on this regimen after hospital discharge despite persistent hypoparathyroidism. Bariatric surgery patients who undergo thyroid surgery require aggressive supplementation to maintain normal serum calcium levels. Preoperative supplementation with calcium and vitamin D is strongly recommended.

Obesity as a Disease.

In recent years, obesity and related medical conditions have become leading public health concerns worldwide. Policy measures to combat or prevent obesity have been instated in a number of countries, with varying degrees of success. To stress the importance of obesity as a health issue, many professional health organizations, including the American Medical Association, have defined obesity itself as a disease. While this may be somewhat controversial, the high risk of comorbid conditions in obese individuals, the significant changes from healthy physiology that are present in the obese state, and the need for further public policies to address the public health threat and economic impact of obesity in the population are strong supporting arguments to label obesity as a disease.

Malnutrition, dehydration, and ancillary feeding options in dysphagia patients.

Patients with dysphagia are at high risk for malnutrition. Several strategies may be used to address the nutritional needs of these patients. Dietary modification, the addition of oral supplements, or the use of nutritional support in the form of enteral tube feeds or parenteral nutrition infusions can greatly impact the overall health of the patient.

The role of bariatric surgery in the treatment of type 2 diabetes: current evidence and clinical guidelines.

The incidence of type 2 diabetes (T2D) continues to rise worldwide. The management of T2D is challenging and therefore amenable to multimodality treatment options. Many published observations of obese individuals with T2D that have undergone bariatric surgery consistently demonstrate remarkable improvement and short-term remission of T2D. Recently published randomized trials confirm these findings and demonstrate significantly improved glycemic control following bariatric procedures, especially Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy. However, the question of long-term remission remains uncertain. Clinicians may consider the use of bariatric surgery as a treatment option for certain obese patients with T2D who have failed intensive lifestyle intervention and conventional pharmacotherapy.

The malnutrition of obesity: micronutrient deficiencies that promote diabetes.

Obesity and diabetes are increasing in prevalence worldwide. Despite excessive dietary consumption, obese individuals have high rates of micronutrient deficiencies. Deficiencies of specific vitamins and minerals that play important roles in glucose metabolism and insulin signaling pathways may contribute to the development of diabetes in the obese population. This paper reviews the current evidence supporting this hypothesis.

Intravenous ibandronate acutely reduces bone hyperresorption in chronic critical illness.

OBJECTIVE: Patients who remain critically ill for prolonged periods and require tracheotomy, defined as chronic critical illness (CCI), display elevated levels of bone resorption. The measurement of bone turnover markers reveals that osteoclastic bone resorption is not only enhanced but also uncoupled from osteoblastic bone formation. We examine the effect of ibandronate on bone turnover in patients with CCI. METHODS: This study is a prospective, double-blind, placebo-controlled trial, in which 20 postmenopausal female participants with CCI were followed for an 11-day period after the administration of a single intravenous dose of ibandronate (3 mg). All participants were treated with ergocalciferol (2000 IU daily), calcium carbonate (1250 mg daily), and calcitriol (0.25 µg daily). RESULTS: The ibandronate group showed a 34% decrease in serum C-telopeptide (CTX) levels (a marker of osteoclastic activity) on day 6, while the placebo group showed a 13% increase (P = .01). By day 11, CTX levels in ibandronate group were not significantly different than baseline or from the placebo group. Osteocalcin (OCN) levels (a marker of osteoblast activity) increased by 78% compared to baseline in the ibandronate group (P = .01) and by 42% in the placebo group (P = .05). There were no significant differences in OCN between the 2 groups throughout the study. Parathyroid hormone levels remained constant throughout the study. No adverse events were observed. CONCLUSION: A single dose of intravenous ibandronate causes a significant but transient reduction in osteoclast activity in patients with CCI, which persists over a 6-day period.

Inpatient enteral and parenteral [corrected] nutrition for patients with diabetes.

Both glycemic control and adequate nutrition support impact the clinical outcome of hospitalized patients. Providing nutrition to malnourished patients using the enteral or parenteral route may increase the risk of hyperglycemia, especially in patients with diabetes. Hyperglycemia can be managed through the use of enteral tube feeds with reduced carbohydrate content or limiting the carbohydrate concentration in parenteral formulas. Judicious use of insulin or other glucose-lowering medications synchronized with appropriate nutrition support allows for optimal inpatient glycemic control.

Bone physiology and therapeutics in chronic critical illness.

Modern medical practices allow patients to survive acute insults and be sustained by machinery and medicines for extended periods of time. We define chronic critical illness as a later stage of prolonged critical illness that requires tracheotomy. These patients have persistent elevations of inflammatory cytokines, diminished hypothalamic-pituitary function, hypercatabolism, immobilization, and malnutrition. The measurement of bone turnover markers reveals markedly enhanced osteoclastic bone resorption that is uncoupled from osteoblastic bone formation. We review the mechanisms by which these factors contribute to the metabolic bone disease of chronic critical illness and suggest potential therapeutics.

Metabolic management following bariatric surgery.

Bariatric surgery is an effective treatment option for obesity. Commonly utilized procedures are either restrictive, malabsorptive, or both. Substantial weight loss can be achieved. Postoperatively, patients experience nutritional, metabolic, and hormonal changes that have important clinical implications. The postoperative diet should be advanced carefully, according to protocol. Micronutrient deficiencies such as vitamin C, vitamin A, and zinc deficiencies are common, especially following malabsorptive procedures. Bone metabolism is greatly affected, in part due to vitamin D deficiency, decreased calcium absorption, and secondary hyperparathyroidism. Diabetes improves acutely in malabsorptive procedures and in sequence with weight loss in restrictive procedures. Polycystic ovarian syndrome improves in nearly all women with this condition who undergo bariatric surgery. Testosterone levels in men also improve after surgery. Consideration of these nutritional, metabolic, and hormonal changes allows for optimal medical management following bariatric surgery.

Impaired postoperative hyperglycemic stress response associated with increased mortality in patients in the cardiothoracic surgery intensive care unit.

OBJECTIVE: To describe the association of tight glycemic control with intensive insulin therapy and clinical outcome among patients in the cardiothoracic surgery intensive care unit. METHODS: All patients who underwent cardiothoracic surgery and were admitted to the cardiothoracic surgery intensive care unit between September 13, 2007, and November 1, 2007, were enrolled. Clinical and metabolic data were prospectively collected. All patients received intensive insulin therapy using a nurse-driven dynamic protocol targeting blood glucose values of 80 to 110 mg/dL. Four stages of critical illness were defined as follows: acute critical illness (intensive care unit days 0-2), prolonged acute critical illness (intensive care unit 3 or more days), chronic critical illness (tracheotomy performed), and recovery (liberated from ventilator). RESULTS: One hundred fourteen patients were enrolled. Seventy-three (64%) recovered during acute critical illness, 26 (23%) recovered during prolonged acute critical illness, and 15 (13%) progressed to chronic critical illness. All 6 deaths were among patients in chronic critical illness. Admission blood glucose and average blood glucose values for the first 12 hours were lower in patients who developed chronic critical illness and died and were higher in patients who developed chronic critical illness and survived (P = .007 and P = .007, respectively). Severe hypoglycemia (blood glucose <40 mg/dL) occurred once (0.03% of all measurements). Lower initial blood glucose values, which reflect an impaired stress response immediately after surgery, were associated with increased mortality, and a significant delay in achieving tight glycemic control with intensive insulin therapy was associated with prolonged intensive care unit course, but no increase in mortality. CONCLUSION: The study findings suggest that acute postoperative hyperglycemia and its prompt correction with intensive insulin therapy are associated with favorable outcomes in patients in the cardiothoracic surgery intensive care unit.

Bromocriptine approved as the first medication to target dopamine activity to improve glycemic control in patients with type 2 diabetes.

Type 2 diabetes mellitus (T2DM) continues to rise in prevalence in the United States and worldwide. Despite advances in medical treatments for T2DM, many patients remain uncontrolled. By targeting centrally mediated pathways of glucose metabolism, bromocriptine represents a novel therapeutic option in T2DM. Several small clinical trials demonstrate improvements in insulin resistance and glycemic control. After the submission of data from four recent, large clinical trials, the US Food and Drug Administration has approved the use of bromocriptine in T2DM. We review the available data from these four trials and other published studies. Bromocriptine is a promising therapy for diabetes patients and demonstrates modest improvements in glycemic control.

Excess thyroid hormone and carbohydrate metabolism.

OBJECTIVE: To review the pertinent basic and clinical research describing the complex effects of excess thyroid hormone on carbohydrate metabolism. METHODS: We performed a MEDLINE search of the English-language literature using a combination of words (ie, "thyrotoxicosis and diabetes," "diabetic ketoacidosis and thyroid storm," "carbohydrate metabolism and hyperthyroid," "glucose homeostasis and thyrotoxicosis") to identify key articles addressing various aspects of the thyroid's influence on carbohydrate metabolism. RESULTS: Thyroid hormone affects glucose homeostasis via its actions on a variety of organs including increased hepatic glucose output, increased futile cycling of glucose degradation products between the skeletal muscle and the liver, decreased glycogen stores in the liver and skeletal muscle, altered oxidative and non-oxidative glucose metabolism, decreased active insulin output from the pancreas, and increased renal insulin clearance. Thyroid hormone also affects adipokines and adipose tissue, further predisposing the patient to ketosis. CONCLUSIONS: Thyrotoxicosis can alter carbohydrate metabolism in a type 2 diabetic patient to such an extent that diabetic ketoacidosis develops if untreated. Based on the current understanding of this relationship, all diabetic patients should be screened for thyroid dysfunction because correcting hyperthyroidism can profoundly affect glucose homeostasis. Similarly, patients presenting in diabetic ketoacidosis should undergo a thyroid function assessment.

Chromium infusion reverses extreme insulin resistance in a cardiothoracic ICU patient.

Insulin resistance is common and often multifactorial in acutely critically ill patients. At our institution, glycemic control is achieved in these patients using an intravenous insulin protocol. The authors present a case in which a patient developed severe insulin resistance following surgical repair of a thoracic aorta aneurysm. Postoperatively, the patient required 2110 units of insulin over 40 hours while receiving pressors and glucocorticoids. After the administration of intravenous chromium at 3 microg/h, the blood sugar normalized and insulin therapy was discontinued. This case represents a unique approach using intravenous chromium to achieve glycemic control in a patient with extreme insulin resistance and acute critical illness. Prospective clinical trials using intravenous chromium may provide the means to optimize intensive insulin therapy for critically ill patients.