LIFE-THREATENING HYPOCALCEMIA IN A PATIENT WITH HIGHLY SUSPECTED OSTEOMALACIA: A CASE REPORT

ABSTRACT: Objective: Osteomalacia is a metabolic bone disease characterized by impaired mineralization with increased non-mineralized osteoid tissue, increased frailty, and reduced bone mineral density. A common cause of osteomalacia in adults and the elderly is severe deficiency of vitamin D, which leads to chronic hypocalcemia, hypophosphatemia, and secondary hyperparathyroidism. The objective of this case report is to describe an unusual clinical presentation of osteomalacia, consisting of life-threatening acute hypocalcemia.Methods: Clinical, laboratory, and imaging data are presented.Results: We report the case of a 65-year-old man that showed symptoms and signs of severe and prolonged hypocalcemia due to unrecognized vitamin D deficiency. He presented at the emergency room reporting abdominal pain and vomiting since the evening before. Blood tests showed increased levels of rhabdomyolysis markers, severe hypocalcemia, hypophosphatemia, hypomagnesemia, normal renal function, elevated levels of alkaline phosphatase, extremely high levels of parathyroid hormone, and hypovitaminosis D. Radiological skeletal features of bone demineralization and bone abnormalities suggestive of osteomalacia were additionally detected. Other secondary causes of hypocalcemia were excluded. Clinical and biochemical resolution were progressively obtained only after an intramuscular loading dose of cholecalciferol was added to the standard calcium intravenous replacement therapy.Conclusion: This case report shows that osteomalacia consequent to a severe vitamin D deficiency can present with acute symptoms and signs of severe hypocalcemia requiring hospital admission. In such cases, vitamin D administration, and not intensive calcium supplementation alone, is essential to achieve clinical resolution of symptoms and normalization of mineral metabolism parameters.Abbreviations: 25-OH-D 25-hydroxyvitamin D CT computed tomography IV intravenous PTH parathyroid hormon

Drug interactions of direct oral anticoagulants in elderly patients with cardiometabolic diseases

In the present review we summarized current knowledge about significant interactions (DIs) of direct oral anticoagulants (DOACs) with other medications frequently prescribed to elderly patients with cardiometabolic diseases. Literature search was performed using PubMed from 1990 to October 2020. Randomized clinical trials (RCTs), subgroup analyses from RCTs, longitudinal studies, case series and case reports were included. Only studies in humans were considered. Elderly was defined as ≥75 years. Assessment of DIs with DOACs is often tricky because of the lack of validated tools to routinely assess magnitude of their anti-coagulation effect. Most of reports in the cardiometabolic area regarded the classes of anti-antiarrhythmic, lipid-lowering and platelet-inhibitors drugs, namely drugs that are widely used to reduce cardiovascular risk in patients with common metabolic diseases. Reports about elderly are limited in general, and it is not known whether certain types of DIs occur more frequently in elderly subjects. DIs were more frequently reported in association with dabigatran, which however has been available for a longer period of time compared with other DOACs. In most cases, no complete information about dosages of medications was available. DIs of DOACs leading to adverse events (both ischemic and bleeding ones) were generally facilitated by older age, polymedication and impaired renal function. Further studies should be carried out to properly investigate DIs of DOACs with cardiometabolic drugs in elderly patients, with particular focus on differences between DOACs and the influence of different dosages

Glucose variability: a new risk factor for cardiovascular disease

Aims and data synthesis: glucose variability (GV) is increasingly considered an additional index of glycemic control. Growing evidence indicates that GV is associated with diabetic vascular complications, thus being a relevant point to address in diabetes management. GV can be measured using various parameters, but to date, a gold standard has not been identified. This underscores the need for further studies in this field also to identify the optimal treatment. Conclusions: We reviewed the definition of GV, the pathogenetic mechanisms of atherosclerosis, and its relationship with diabetic complications

Prevalence and risk of new-onset diabetes mellitus after COVID-19: a systematic review and meta-analysis

AimsAfter the acute phase of SARS-CoV-2 infection, the onset of glycemic impairment and diabetes have been reported. Nevertheless, the exact burden of glycemic impairment and diabetes after COVID-19 has not been clearly described.Materials and methodsElectronic search was run in Pubmed (MEDLINE), Web of Science, Scopus, and ClinicalTrial.org for reports published from database inception to September 2022. We included observational studies reporting quantitative data on diabetes prevalence or its onset in subjects with a history of SARS-CoV-2 infection from at least 60 days. Risk of bias was assessed by the JBI’s critical appraisal checklist. Random effect model was used to calculate pooled data. The review protocol was registered on PROSPERO (CRD42022310722).ResultsAmong 1,630 records screened, 20 studies were included in the analysis. The mean or median age of participants ranged from ~ 35 to 64 years, with a percentage of males ranging from 28% to 80%. Only two studies were considered at low risk of bias. The estimate of diabetes prevalence, calculated on a total of 320,948 participants pooled with 38,731 cases, was 16% (95%CI: 11-22%). The estimate of proportion of incident cases of diabetes was 1.6% (95%CI: 0.8-2.7%). Subgroup analysis showed that previous hospitalization increased the prevalence of diabetes and the proportion of incident cases.ConclusionDiabetes is common in individuals who have experienced SARS-CoV-2 infection, especially if they required hospitalization. This data may be helpful to screen for diabetes and manage its complications in individuals who experienced COVID-19.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022310722, identifier CRD42022310722

Diet Rich in Plant Protein May Prevent Type 2 Diabetes

Purpose : The aim is to show the ideal protein quality and quantity and the dietary composition for the prevention and metabolic control of type 2 diabetes mellitus (T2DM). Introduction Although some reviews demonstrate the advantages of a diet with a higher protein intake, other reviews have observed that a diet high in carbohydrates, with low-glycaemic index carbohydrates and good fibre intake, is equally effective in improving insulin sensitivity. Methods Over 2831 articles were screened, and 24 from the last 5 years were analysed and summarised for this review, using the protein, diabetes and insulin glucose metabolic keywords in Pubmed in June 2019. Results Eleven studies demonstrate that a higher consumption of proteins has a positive effect on insulin sensitivity. A higher intake of animal protein seems to be related to an increased risk of T2DM. Four studies show that consumption of meat has a deleterious effect. Higher intake of plant protein and dairy products is associated with a modestly reduced risk. Discussion Based on the results obtained, for the prevention of T2DM and all disorders related to metabolic syndrome, no ideal dietary composition has yet been found. The advantage of plant protein sources may be related to the foods' low-glycaemic index due to the high fibre content. However, the right protein quality (animal and plant) and the quantity for T2DM prevention and metabolic control are unclear and need to be investigated with further long-term studies

Insulin autoimmune syndrome in an Argentine woman taking α-lipoic acid: A case report and review of the literature.

Insulin autoimmune syndrome is an unusual cause of spontaneous hypoglycaemia in non-Asian populations. In the majority of cases, this syndrome appears a few weeks after the administration of drugs containing a sulfhydryl group. A strong association between this syndrome and HLA-DR4 has been shown. Only seven cases have been described in non-Asian patients. We report the first case of insulin autoimmune syndrome in an Argentine woman taking alfa-lipoic acid. She developed hypoglycaemic symptoms approximately 1 month after starting therapy. Blood sampling collected during an episode of symptomatic hypoglycaemia showed low blood glucose level (2.39 mmol/L), high level of serum insulin (1971.55 pmol/L), inappropriately high level of C-peptide (2.36 nmol/L) and high levels of insulin antibodies (274.78 IU/mL). HLA-DNA typing identified DRB1*04:03. Due to the widespread use of alfa-lipoic acid for its antioxidant properties, clinicians should be aware that it may trigger an autoimmune hypoglycaemia in people with a genetic predisposition

Short-term treatment with atorvastatin reduces platelet CD40 ligand and thrombin generation in hypercholesterolemic patients

Background - Soluble CD40L (sCD40L), a substance that maximally reflects in vivo platelet activation, is increased in patients with hypercholesterolemia. We investigated the relation between sCD40L and platelet CD4OL in hypercholesterolemic patients before and after a short-term treatment with atorvastatin. Methods and Results - Collagen-induced platelet CD40L and plasma levels of sCD40L and prothrombin fragment F1+2, a marker of thrombin generation, were investigated in 30 hypercholesterolemic patients and 20 healthy subjects. Hypercholesterolemic patients were then randomized to either diet ( n = 15; group A) or atorvastatin 10 mg/d ( group B); the aforementioned variables were measured at baseline and after 3 days of treatment. Compared with referents, hypercholesterolemic patients showed higher values of platelet CD40L ( P < 0.005), sCD40L ( P < 0.005), and F1 + 2 ( P < 0.003). Platelet CD40L was significantly correlated with sCD40L ( P < 0.001), and the latter was significantly correlated with F1 + 2 ( P < 0.001). The intervention trial showed no changes in group A but a significant decrease in platelet CD40L ( P < 0.01), sCD40L ( P < 0.002), and F1 + 2 ( P < 0.03) in group B. In vitro studies demonstrated that cholesterol enhanced platelet CD40L and CD40L-mediated clotting activation by human monocytes; also, atorvastatin dose-dependently inhibited platelet CD40L expression and clotting activation by CD40L-stimulated monocytes. Conclusions - This study shows that, in hypercholesterolemia, platelet overexpression of CD40L may account for enhanced plasma levels of sCD40L and F1 + 2. Atorvastatin exerts a direct antithrombotic effect via inhibition of platelet CD40L and CD40L-mediated thrombin generation, independently of its cholesterol-lowering effect

Long-Term Iron and Vitamin B12 Deficiency Are Present after Bariatric Surgery, Despite the Widespread Use of Supplements

There are few long-term nutritional studies in subjects undergoing bariatric surgery that have assessed weight regain and nutritional deficiencies. In this study, we report data 8 years after surgery on weight loss, use of dietary supplements and deficit of micronutrients in a cohort of patients from five centres in central and northern Italy. The study group consisted of 52 subjects (age: 38.1 +/- 10.6 y, 42 females): 16 patients had Roux-en-Y gastric bypass (RYGB), 25 patients had sleeve gastrectomy (SG) and 11 subjects had adjustable gastric banding (AGB). All three bariatric procedures led to sustained weight loss: the average percentage excess weight loss, defined as weight loss divided by excess weight based on ideal body weight, was 60.6% +/- 32.3. Despite good adherence to prescribed supplements, 80.7% of subjects (72.7%, AGB; 76.7%, SG; 93.8 %, RYGB) reported at least one nutritional deficiency: iron (F 64.3% vs. M 30%), vitamin B12 (F 16.6% vs. M 10%), calcium (F 33.3% vs. M 0%) and vitamin D (F 38.1% vs. M 60%). Long-term nutritional deficiencies were greater than the general population among men for iron and among women for vitamin B12

Model Predictive Control for Building Active Demand Response Systems

The Active Demand Response (ADR), integrated with the distributed energy generation and storage systems, is the most common strategy for the optimization of energy consumption and indoor comfort in buildings, considering the energy availability and the balancing of the energy production from renewable sources. In the paper an overview of basic requirements and applications of ADR management is presented. Specifically, the model predictive control (MPC) adopted in several applications as optimal control strategy in the ADR buildings context is analysed. Finally the research experience of the authors in this context is described