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Most deaths from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection occur in older subjects. We assessed the utility of serum inflammatory markers interleukin-6 (IL-6), C reactive protein (CRP), and ferritin (Roche, Indianapolis, IN), and SARS-CoV-2 immunoglobulin G (IgG), immunoglobulin M (IgM), and neutralizing antibodies (Diazyme, Poway, CA). In controls, non-hospitalized subjects, and hospitalized subjects assessed for SARS-CoV-2 RNA (n = 278), median IgG levels in arbitrary units (AU)/mL were 0.05 in negative subjects, 14.83 in positive outpatients, and 30.61 in positive hospitalized patients (PPP = 1.00 x 10−12). Antibody or ferritin levels did not add significantly to predicting hospitalization. Antibody testing in family members and contacts of SARS-CoV-2 RNA positive cases (n = 759) was invaluable for case finding. Persistent IgM levels were associated with chronic COVID-19 symptoms. In 81,624 screened subjects, IgG levels were positive (≥1.0 AU/mL) in 5.21%, while IgM levels were positive in 2.96% of subjects. In positive subjects median IgG levels in AU/mL were 3.14 if P = 2.96 x 10−38). Our data indicate that: 1) combined IL-6 ≥10 pg/mL and CRP ≥10 mg/L identify SARS-CoV-2 positive subjects requiring hospitalization; 2) IgG levels were significantly correlated with neutralizing antibody levels with a wide range of responses; 3) IgG levels have significant utility for case finding in exposed subjects; 4) persistently elevated IgM levels are associated with chronic symptoms; and 5) IgG levels are significantly higher in positive older subjects than their younger counterparts.

Most deaths from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection occur in older subjects. We assessed age effects and clinical utility of serum SARS-CoV-2 immunoglobulin G (IgG), immunoglobulin M (IgM), and neutralizing antibodies and serum inflammatory markers. Serum IgG, IgM, and neutralizing antibody levels were measured using chemiluminescence assays from Diazyme (Poway, CA), while serum interleukin-6 (IL-6), C reactive protein (CRP), and ferritin were measured with immunoassays obtained from Roche (Indianapolis, IN). In 79,005 subjects, IgG and IgM levels were positive (≥1.0 arbitrary units [AU]/mL) in 5.29% and 3.25% of subjects, respectively. In antibody positive subjects, median IgG levels were 3.93 AU/mL if >1.0 AU/mL occurred in 97.7% of inpatients versus 1.8% of outpatients (>50-fold relative risk, C statistic 0.986, p

Lower extremity arterial disease affects more than 200 × 10e6 people worldwide causing Critical Limb Ischemia (CLI), also referred to as chronic limb-threatening ischemia (CLTI) a life-threatening disease and the major cause of ischemic amputation. For nonrevascularizable patients, the outlook is bleak and novel therapies are needed. This chapter discusses new approaches including gene therapy and stem/progenitor cell (SPC)-based therapies, including autologous bone marrow-derived cells (BM), MB-mononuclear cells (BM-MNC), mesenchymal stem cells (MSC), mobilized bone marrow cell (PB-MNC), allogeneic cells and ex vivo expanded or activated/differentiated cell products. A preliminary first-in-human trial of a novel treatment is presented that combines immune cell therapy and a stepwise activation and differentiation of SPC. Cells from a standard blood draw (with no pretreatment or mobilization) are transformed, within a day, into a therapeutic product (BGC101) composed of endothelial progenitor cells (EPCs), SPCs, dendritic cells (DCs), and T helper cells. BGC101 was found safe and effective in stabilizing and reversing the course of CLI. Controlled studies on a larger population are planned to evaluate this new concept.

Intermittent fasting is increasing in popularity as a means of losing weight and controlling chronic illness. Patients with diabetes mellitus, both types 1 and 2, comprise about 10% of the population in the United States and would likely be attracted to follow one of the many methods of intermittent fasting. Studies on the safety and benefits of intermittent fasting with diabetes are very limited though, and health recommendations unfortunately today arise primarily from weight loss gurus and animal studies. Medical guidelines on how to manage therapeutic intermittent fasting in patients with diabetes are non-existent. The evidence to build such a clinical guideline for people with a diabetes diagnosis is almost non-existent, with just one randomized trial and several case reports. This article provides an overview of the available knowledge and a review of the very limited pertinent literature on the effects of intermittent fasting among people with diabetes. It also evaluates the known safety and efficacy issues surrounding treatments for diabetes in the fasting state. Based on those limited data and a knowledge of best practices, this paper proposes expert-based guidelines on how to manage a patient with either type 1 or 2 diabetes who is interested in intermittent fasting. The safety of each relevant pharmaceutical treatment during a fasting period is considered. When done under the supervision of the patient’s healthcare provider, and with appropriate personal glucose monitoring, intermittent fasting can be safely undertaken in patients with diabetes.

Hypoglycemia is the major side effect of insulin therapy. The elderly are especially vulnerable to episodes of hypoglycemia, and with greater risks of complications such as falls. Two new long-acting basal insulins, glargine-300 (Gla-300) and degludec, are associated with lower incidences of hypoglycemia than previously available basal insulins. One of them, Gla-300, was studied in the elderly and has a lower incidence of hypoglycemia in patients over 65 years old. These new data should be incorporated into decision making when treating the elderly patient with insulin, whether they have type 1 or 2 diabetes. Abbreviations: A1c = glycated hemoglobin A1c Gla-100 = glargine 100 U/mL Gla-300 = glargine 300 U/mL GLP-1 RA = glucagon-like peptide-1 receptor analogue

In August 2003, I wrote a commentary entitled "How Long Can a Vial of Insulin be Used After It Is Started." The commentary included comments from each of the 3 insulin manufacturers, as well as the American Diabetes Association. Anyone reading the article quickly realized that there was little agreement among the insulin manufacturers and just as little clarity to this question. Over the ensuing 10 years, there has been little or no effort made by either the Food and Drug Administration (FDA) or the insulin manufacturers to clarify this issue of insulin storage after a bottle is started. Current package inserts list varying times from 28 to 42 days, while the latest recommendation from the American Diabetes Association gives a uniform 1-month time limit. I would therefore propose that insulin manufacturers begin putting on every insulin vial and pen, in addition to the expiration date, the amount of time that particular insulin should be used after it is started. In addition there should be a box for the patient to write the starting date directly onto the vial or pen. This would eliminate the need for uniformity of recommendations; all the patient would have to do is read the instructions written on the insulin vial or pen.

To create guidelines for patients with diabetes to fast safely on Yom Kippur and other Jewish fast days, with the primary goal of avoiding hypoglycemia.Almost 30 years of experience in endocrinology and the pharmacokinetics and pharmacodynamics of current drug therapy were applied to develop these guidelines and recommendations. A few illustrative cases are presented.Patients with either type 1 or type 2 diabetes were able to fast safely when a treatment plan was proactively formulated before the fast day. An understanding of which medications lower basal and which lower prandial blood glucose levels, as well as their duration of action, is critical.The overwhelming majority of patients with type 1 or type 2 diabetes can, from the perspective of blood glucose control, safely fast on Yom Kippur. Physician-patient discussion is important to prevent the patient from relying only on personal judgment and potentially taking too much medication, with the resultant development of hypoglycemia.

Women with a history of gestational diabetes are at high risk for developing type 2 diabetes mellitus. In studies with long periods of follow-up, diabetes incidence of up to 70% has been reported. The appropriate follow-up of women following a pregnancy complicated by gestational diabetes has not been studied. Published guidelines recommend that obstetrician/gynaecologists, who are often the de facto primary care physicians for these otherwise healthy young women, incorporate glucose monitoring in the post-partum period into their annual examinations. In reality, reported rates of screening have been low. There is also no clear evidence for any beneficial interventions to prevent diabetes in patients with prior history of gestational diabetes. Lifestyle intervention programmes for diabetes prevention among these patients yielded disappointing results. Metformin, pioglitazone, liraglutide, and bariatric surgery are possible options but based on inadequate data. There remains a need for randomized, placebo-controlled studies to evaluate various pharmacologic treatments, with and without lifestyle interventions, to prevent type 2 diabetes mellitus in women with a history of gestational diabetes.

This commentary constitutes the opinions of the endocrinologists whose names are appended. The commentary is based on articles published in peer-reviewed journals as listed in the cited references, as well as cumulative experience in treating patients with type 1 diabetes mellitus (T1DM). This commentary applies only to patients with T1DM, and does not apply to patients with type 2 DM who are being treated with insulin even though the principles may be similar. The recommendations outlined also do NOT apply to the pregnant woman with T1DM, who should not fast. Additionally, this commentary does not preclude an individual from directing any questions having to do with religious observance to a competent Rabbi. For example, with regard to fingerstick blood glucose testing, which requires the use of an electronic meter, we have received written council from Rabbi Yosef Shalom Eliashiv and Rabbi Joseph Efrati (Jerusalem, Israel), and Rabbi M. Weissmandl and Rabbi Mordechai Willig (NY) that the procedure is permissible when performed appropriately for the patient's welfare and health while fasting on Yom Kippur.

To report the first case of central diabetes insipidus associated with hemophagocytic lympho-histiocytosis.We describe the clinical course of a 75-year-old woman who developed febrile illness 1 month after receiving the H1N1 influenza vaccination. Shortly thereafter, she developed central diabetes insipidus, which responded to treatment with intranasal desmopressin acetate. She was then hospitalized with another febrile illness and diagnosed with hemophagocytic lymphohistiocytosis.Magnetic resonance imaging of the pituitary gland was significant for plaquelike meningeal enhancement and thickening surrounding the infundibulum, which has been previously reported as a manifestation of histiocytosis.We believe this is the first case of central diabetes insipidus associated with hemophagocytic lymphohistiocytosis.

Patients with diabetes may undergo an approximately 24-h fast for a voluntary religious observance or in preparation for a medical procedure. Commonly, patients will manage their diabetes before and during such fasting without guidelines from their doctors, often because they did not ask for advice. The physician should therefore take the lead in advising patients how to fast safely, in order to avoid the situation wherein the patient manages medication changes on his/her own. Furthermore, it sends a message to the patient that having diabetes does not preclude living a reasonably ‘normal’ life, even when it comes to religious observances. Copyright © 2011 John Wiley & Sons, Ltd.

Editor’s comment : The commentary by Dr. Grajower has such important clinical relevance that responses were invited from the three pharmaceutical companies that supply insulin in the U.S. and the American Diabetes Association, and all of these combined in this commentary. The commenting letter and individual responses were authored separately and are completely independent of each other. Diabetic patients treated with insulin, whether for type 1 or type 2 diabetes, are prone to often unexplained swings in their blood glucose. These swings can vary from dangerously low to persistently high levels. Most diabetic patients, and most physicians, will adjust insulin regimens so as to avoid hypoglycemia at the expense of hyperglycemia. Among the “textbook” reasons for variable glucose responses to any given insulin regimen are 1 ) site of administration, 2 ) exercise, 3 ) bottles not adequately mixed before drawing the insulin (for NPH, Lente, or Ultralente), and 4 ) duration of treatment with insulin (1). A new insulin was marketed by Aventis Pharmaceuticals about 1 year ago, insulin glargine (Lantus). The manufacturer seemed to stress that patients not use a started bottle of this insulin for >28 days (2). Two patients of mine highlighted this point. L.K. is a 76-year-old woman with type 2 diabetes, diagnosed at 55 years of age, and treated with insulin since age 56. Her insulin regimen was changed to Lantus at night together with Novolog before meals. She monitors her blood glucose four times a day. She used a bottle of Lantus until it ran out; therefore, a bottle lasted for 2 months. Her recent HbA1c was 7.6%. I retrospectively analyzed her home glucose readings by averaging her fasting blood glucose levels for the first 15 days of a new bottle and the last 15 days of that same bottle. The results were 137 ± …

Objective To report a case of life-threatening hyponatremia as a complication of a 4-week long low-iodine diet and highlight the risk factors for this complication by reviewing all previously reported cases. Methods The clinical and biochemical data from the study patient are presented and the pertinent literature is reviewed. A risk analysis for this complication is highlighted. Results A 66-year-old Vietnamese woman had a total thyroidectomy and bilateral neck lymph node dissection for papillary thyroid carcinoma. A whole body radioiodine scan demonstrated 2 foci of activity in the anterior neck. The patient received recombinant human thyrotropin (rhTSH) and was admitted for radioiodine therapy. She had strictly adhered to a low-iodine diet for 4 weeks in preparation for ablation. The patient was on a thiazide diuretic for her hypertension, which was discontinued on admission. On admission, the patient started feeling light-headed, dizzy, and nauseated. Blood tests revealed a critical serum sodium concentration of 107 mEq/L. Further investigations confirmed hypotonic hyponatremia, which had developed despite being euthyroid after receiving rhTSH. The patient was managed accordingly and made a full recovery. Conclusions This case, in addition to the reviewed cases, emphasizes the importance of preventing and managing this rare but relatively dangerous complication. Based on an analysis of the reviewed cases, the risk factors for developing this complication are a prolonged low-iodine diet, the elimination of salt from the diet, and the use of thiazide diuretics. All patients in the reported cases were older than 65 years of age. (Endocr Pract. 2011;17:e113-e117)

The concentration of hepatic nuclear T3 receptors was measured in isolated nuclei from athyreotic mice bearing thyrotrophic tumors and intact rats with Walker 256 carcinoma. Receptor concentration was reduced in all tumor-bearing animals. The mean receptor capacity of the Walker tumor-bearing rats [0.31 +/- 0.05 (SEM) ng/mg DNA] was significantly decreased from simultaneously assayed controls (0.47 +/- 0.04 ng/mg DNA; P less than 0.01). No change in the apparent equilibrium association constant was observed. In individual rats, the magnitude of the decrease in nuclear T3 receptor concentration was highly correlated with the decrease in tumor-free body weight. Additional studies showed that the decrease in nuclear receptors was not due to delayed equilibration of added T3 with nuclear sites in vitro or to an increase in endogenous hepatic T3 concentration. The plasma concentration of total and free T4 and T3 was decreased in tumor-bearing rats. Plasma TSH concentration, however, remained unchanged. Thus, these transplantable neoplasms seem to be associated with decreased hepatic nuclear receptors and low concentrations of plasma thyroid hormones. The unchanged plasma TSH suggests that the animals remained euthyroid.

We have observed six episodes of severe symptomatic hypoglycemia in 5 nondiabetic patients on chronic maintenance hemodialysis. The common factor in all 5 patients was propranolol administration for the treatment of hypertension. This observation suggests that beta-adrenergic blockade may cause profound hypoglycemia in dialyzed patients with other predisposing factors such as poor nutrition, liver dysfunction or stress. On the basis of our experience, we recommend blood sugar determinations for propranolol-treated patients during dialysis against glucose-free dialysate.

The activity of hepatic α-glycerophosphate dehydrogenase (α-GPD) and malic enzyme (ME) was measured in rats bearing the Walker 256 carcinoma to assess the relationship between the reduction in the nuclear L-T3 (T3) receptor concentration which occurs in tumor-bearing (T) rats and the biological effects of thyroid hormones. T3 receptor concentration was uniformly decreased when tumors exceeded 9.5% of body weight. No change in basal α-GPD activity was observed, but ME activity was decreased to between 29–61% of control. The decrease in ME activity did not appear to be related to decreased nuclear T;) receptor concentration since ME was also decreased in T rats with tumors that were too small to effect a decrease in the concentration of nuclear T3 receptors or plasma T4 and T3. The response of both ME and α-GPD to T3 administration in T rats was comparable to that of control despite reduced nuclear T3 receptor and plasma hormone concentrations. When non-T rats were subjected to food restriction to simulate ...

Excerpt To the editor: I write to add to the report of Dat and Sontag (1) with a brief description of another family with pancreatic carcinoma. I treated an 80-year-old white man who presented with...