Long-Term Safety and Efficacy of Recombinant Human Parathyroid Hormone (1-84) in Adults With Chronic Hypoparathyroidism.

Context: Chronic hypoparathyroidism is conventionally treated with oral calcium and active vitamin D to reach and maintain targeted serum calcium and phosphorus levels, but some patients remain inadequately controlled.

Objective: To assess long-term safety and efficacy of recombinant human parathyroid hormone (1-84) (rhPTH(1-84)) treatment.

Methods: This was an open-label extension study at 12 US centers.

Risk of Cardiovascular Conditions in Patients with Chronic Hypoparathyroidism: A Retrospective Cohort Study.

Introduction: In patients with chronic hypoparathyroidism disordered calcium homeostasis has been associated with risk of cardiovascular diseases, including cardiomyopathy, congestive heart failure, and arrhythmia; however, larger-scale studies are needed to examine these risks. This study evaluated the risk of cardiovascular conditions among patients with chronic hypoparathyroidism.

Methods: Adults with and without chronic hypoparathyroidism were selected from a medical insurance claims database in the USA from January 2007 to June 2017, and were followed for up to 5 years.

Risk of Nephrolithiasis and Nephrocalcinosis in Patients with Chronic Hypoparathyroidism: A Retrospective Cohort Study.

Introduction: Chronic hypoparathyroidism managed with conventional treatment, comprising oral administration of calcium and active vitamin D, has been associated with renal complications, including nephrolithiasis and nephrocalcinosis. Further larger-scale studies are needed to examine these risks. This study evaluated the risk of nephrolithiasis and nephrocalcinosis in patients with chronic hypoparathyroidism.

Risk of Chronic Kidney Disease and Estimated Glomerular Filtration Rate Decline in Patients with Chronic Hypoparathyroidism: A Retrospective Cohort Study.

Introduction: Chronic hypoparathyroidism, treated with conventional therapy of oral calcium supplements and active vitamin D, may increase the risk of kidney complications. This study examined risks of development and progression of chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) decline in patients with chronic hypoparathyroidism.

Methods: A retrospective cohort study using a managed care claims database in the United States from January 2007 to June 2017 included patients with chronic hypoparathyroidism (excluding those receiving parathyroid hormone) and randomly selected patients without hypoparathyroidism followed for up to 5 years.

Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism.

Context: Conventional hypoparathyroidism treatment with oral calcium and active vitamin D is aimed at correcting hypocalcemia but does not address other physiologic defects caused by PTH deficiency.

Objective: To evaluate long-term safety and tolerability of recombinant human PTH (1-84) [rhPTH(1-84)].

Design: Open-label extension study; 5-year interim analysis.

Long-term toxic effects of proton radiotherapy for paediatric medulloblastoma: a phase 2 single-arm study.

Background: Compared with traditional photon radiotherapy, proton radiotherapy irradiates less normal tissue and might improve health outcomes associated with photon radiotherapy by reducing toxic effects to normal tissue. We did a trial to assess late complications, acute side-effects, and survival associated with proton radiotherapy in children with medulloblastoma.

Methods: In this non-randomised, open-label, single-centre, phase 2 trial, we enrolled patients aged 3-21 years who had medulloblastoma.

Alefacept provides sustained clinical and immunological effects in new-onset type 1 diabetes patients.

Background: Type 1 diabetes (T1D) results from destruction of pancreatic β cells by autoreactive effector T cells. We hypothesized that the immunomodulatory drug alefacept would result in targeted quantitative and qualitative changes in effector T cells and prolonged preservation of endogenous insulin secretion by the remaining β cells in patients with newly diagnosed T1D.

Methods: In a multicenter, randomized, double-blind, placebo-controlled trial, we compared alefacept (two 12-week courses of 15 mg/wk i.

Targeting of memory T cells with alefacept in new-onset type 1 diabetes (T1DAL study): 12 month results of a randomised, double-blind, placebo-controlled phase 2 trial.

Background: Type 1 diabetes results from autoimmune targeting of the pancreatic β cells, likely mediated by effector memory T (Tem) cells. CD2, a T cell surface protein highly expressed on Tem cells, is targeted by the fusion protein alefacept, depleting Tem cells and central memory T (Tcm) cells. We postulated that alefacept would arrest autoimmunity and preserve residual β cells in patients newly diagnosed with type 1 diabetes.

Teplizumab preserves C-peptide in recent-onset type 1 diabetes: two-year results from the randomized, placebo-controlled Protégé trial.

Protégé was a phase 3, randomized, double-blind, parallel, placebo-controlled 2-year study of three intravenous teplizumab dosing regimens, administered daily for 14 days at baseline and again after 26 weeks, in new-onset type 1 diabetes. We sought to determine efficacy and safety of teplizumab immunotherapy at 2 years and to identify characteristics associated with therapeutic response. Of 516 randomized patients, 513 were treated, and 462 completed 2 years of follow-up.

Teplizumab for treatment of type 1 diabetes (Protégé study): 1-year results from a randomised, placebo-controlled trial.

Background: Findings of small studies have suggested that short treatments with anti-CD3 monoclonal antibodies that are mutated to reduce Fc receptor binding preserve β-cell function and decrease insulin needs in patients with recent-onset type 1 diabetes. In this phase 3 trial, we assessed the safety and efficacy of one such antibody, teplizumab.

Methods: In this 2-year trial, patients aged 8-35 years who had been diagnosed with type 1 diabetes for 12 weeks or fewer were enrolled and treated at 83 clinical centres in North America, Europe, Israel, and India.

Management of diabetic ketoacidosis in children and adolescents.

Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes mellitus. While it can occur in all types of diabetes mellitus, it is seen most often in patients with type 1 diabetes, either at presentation or as a result of non-compliance with medical therapy. DKA is characterized by hyperglycemia, acidosis, dehydration, and electrolyte abnormalities, which result from a deficiency of insulin and an excess of counter-regulatory hormones.

Exendin-4 improves reversal of diabetes in NOD mice treated with anti-CD3 monoclonal antibody by enhancing recovery of beta-cells.

Immune modulators can arrest loss of insulin secretion in type 1 diabetes mellitus (T1DM), but they have not caused permanent disease remission or restored normal insulin secretion. We tested whether exendin-4, a glucagon-like peptide-1 receptor agonist, would enhance remission of T1DM in NOD mice treated with anti-CD3 monoclonal antibody (mAb) and studied the effects of exendin-4 treatment on cellular and metabolic responses of beta-cells. Diabetic NOD mice treated with anti-CD3 mAb and exendin-4 had a higher rate of remission (44%) than mice treated with anti-CD3 mAb alone (37%) or exendin-4 (0%) or insulin or IgG alone (0%) (P < 0.

Autoimmunity and beta cell regeneration in mouse and human type 1 diabetes: the peace is not enough.

Accumulating data from animal models of type 1 diabetes and some findings from clinical studies suggest that autoimmune destruction of islet beta cells is associated with enhanced beta cell regeneration. Successful immune therapies, aimed at preservation of islet cell mass, result in a remarkable reduction of beta cell regeneration. Treated or not, as long as the task of treatment is limited by "making peace" with autoimmunity, the process of beta cell loss continues.

Effects of autoimmunity and immune therapy on beta-cell turnover in type 1 diabetes.

beta-Cell mass can expand in response to demand: during pregnancy, in the setting of insulin resistance, or after pancreatectomy. It is not known whether similar beta-cell hyperplasia occurs following immune therapy of autoimmune diabetes, but the clinical remission soon after diagnosis and the results of recent immune therapy studies suggest that beta-cell recovery is possible. We studied changes in beta-cell replication, mass, and apoptosis in NOD mice during progression to overt diabetes and following immune therapy with anti-CD3 monoclonal antibodies (mAbs) or immune regulatory T-cells (Tregs).

Clinical and metabolic characteristics of an obese, Dominican, pediatric population.

The prevalence of obesity is particularly high in Black and Latino pediatric populations. A limited number of metabolic studies suggest that race plays a role in the development of obesity-related co-morbidities. We evaluated clinical and metabolic characteristics of 428 obese (mean BMI z-score 2.

Natural history of beta-cell function in type 1 diabetes.

Despite extensive and ongoing investigations of the immune mechanisms of autoimmune diabetes in humans and animal models, there is much less information about the natural history of insulin secretion before and after the clinical presentation of type 1 diabetes and the factors that may affect its course. Studies of insulin production previously published and from the Diabetes Prevention Trial (DPT)-1 suggest that there is progressive impairment in insulin secretory responses but the reserve in response to physiological stimuli may be significant at the time of diagnosis, although maximal responses are more significantly impaired. Other factors, including insulin resistance, may play a role in the timing of clinical presentation along this continuum.