Rickets Types and Treatment with Vitamin D and Analogues.

The definition of "Vitamin D" encompasses a group of fat-soluble steroid compounds of different origins with similar chemical structures and the same biological effects. Vitamin D deficiency and/or a defect in the process of its synthesis or transport predispose individuals to several types of rickets. In addition to cholecalciferol, ergocalciferol, and vitamins D3 and D2, there are also active metabolites for the treatment of this condition which are commercially available. Calcitriol and aphacalcidiol are active metabolites that do not require the renal activation step, which is required with calcifediol, or hepatic activation. The purpose of this review is to summarize current approaches to the treatment of rickets for generalist physicians, focusing on the best vitamin D form to be used in each type, or, in the case of X-linked hypophosphatemic rickets (XLH), on both conventional and innovative monoclonal antibody treatments.

Alkaline phosphatase in clinical practice in childhood: Focus on rickets.

Serum alkaline phosphatase (ALP) and its isoenzymes reflect bone metabolism: ALP increases the ratio of inorganic phosphate to pyrophosphate systemically and facilitates mineralization as well as reduces extracellular pyrophosphate concentration, an inhibitor of mineral formation. On the contrary, low ALP activity is associated with reduction of bone turnover. ALP includes four isoenzymes depending on the site of tissue expression: intestinal ALP, placental ALP, germ cell ALP and tissue nonspecific ALP or liver/bone/kidney ALP. The bone isoenzyme (B-ALP) is involved in bone calcification and is a marker of bone turnover as a result of osteoblastic activity. ALP and its isoenzymes are crucial in the diagnostic process of all the forms of rickets.The most common cause of rickets is vitamin D nutritional deficiency. The aim of this review is to update on the role played by ALP serum concentrations as a relevant marker in thediagnosis and treatment of rickets. Indeed, the diagnosis of rickets is based on its clinical, radiological and laboratory characteristics. An elevated ALP level is one of the markers for the diagnosis of rickets in children, though it is also associated with bone formation process. ALP is also useful for the differentiation between rickets and other disorders that can mimic rickets because of their clinical and laboratory characteristics, and, together with other biochemical markers, is crucial for the differential diagnosis of the different forms of rickets. Age, severity and duration of rickets may also modulate ALP elevation. Finally, ALP measurements are useful in clinical and therapeutic follow-up.

Safe Perinatal Management of Neonates Born to SARS-CoV-2 Positive Mothers at the Epicenter of the Italian Epidemic.

Introduction: 2019-novel Coronavirus Disease (COVID-19) pandemic has recently struck Northern Italy. Limited data are available about COVID-19 during pregnancy and infancy, mostly from China. Herein, our experience on a safe perinatal management of neonates born to COVID-19 mothers is reported. Method: Since late February through May 15, 2020, 375 pregnant women delivered at our City Hospital in Piacenza, at the epicenter of the Italian epidemic. Of these, 144 were tested via a SARS-CoV-2 quantitative rRT-PCR nasopharyngeal swab prior to delivery, firstly on the basis of epidemiological and clinical criteria, then adopting a universal screening approach. All newborns from SARS-CoV-2 positive mothers were tested via nasopharyngeal swab at birth, on day 3 and/or day 7. In case of positive result, they were re-tested on day 14. Results: Fifteen women tested positive for SARS-CoV-2 infection. All newborns except one were born at term. All of them were non-infected at birth, irrespective of mode of delivery; 13 out 15 remained negative; the two positive neonates became negative by day 14 of life. All of them have always remained asymptomatic. All newborns except two were allowed to have immediate bonding, permanent rooming-in, and direct breastfeeding. Conclusions: Our study supports the claim that COVID-19 in pregnancy is not associated with worse clinical outcomes compared to non-COVID-19 pregnant women and/or with higher rates of preterm birth and intrauterine growth restriction. Intrauterine vertical transmission of SARS-CoV-2 seems to be unlikely. Breastfeeding appears to be safe and protective for the neonate, once appropriate preventive measures are adopted.

Prostaglandin E2 Stimulates the Expansion of Regulatory Hematopoietic Stem and Progenitor Cells in Type 1 Diabetes.

Hematopoietic stem and progenitor cells (HSPCs) are multipotent stem cells that have been harnessed as a curative therapy for patients with hematological malignancies. Notably, the discovery that HSPCs are endowed with immunoregulatory properties suggests that HSPC-based therapeutic approaches may be used to treat autoimmune diseases. Indeed, infusion with HSPCs has shown promising results in the treatment of type 1 diabetes (T1D) and remains the only "experimental therapy" that has achieved a satisfactory rate of remission (nearly 60%) in T1D. Patients with newly diagnosed T1D have been successfully reverted to normoglycemia by administration of autologous HSPCs in association with a non-myeloablative immunosuppressive regimen. However, this approach is hampered by a high incidence of adverse effects linked to immunosuppression. Herein, we report that while the use of autologous HSPCs is capable of improving C-peptide production in patients with T1D, ex vivo modulation of HSPCs with prostaglandins (PGs) increases their immunoregulatory properties by upregulating expression of the immune checkpoint-signaling molecule PD-L1. Surprisingly, CXCR4 was upregulated as well, which could enhance HSPC trafficking toward the inflamed pancreatic zone. When tested in murine and human in vitro autoimmune assays, PG-modulated HSPCs were shown to abrogate the autoreactive T cell response. The use of PG-modulated HSPCs may thus provide an attractive and novel treatment of autoimmune diabetes.

Rapunzel syndrome: an infrequent cause of severe iron deficiency anemia and abdominal pain presenting to the pediatric emergency department.

BACKGROUND: Iron deficiency anemia (IDA) and abdominal pain are commonly seen in a pediatric emergency department (8 and 18% incidence respectively in our center). They are manifestations of a wide variety of diseases ranging from benign to immediately life-threatening. Trichobezoar is an under-diagnosed entity that has to be considered in children and adolescents, expecially female, suffering from trichotillomania (compulsion to pull hair) and trichophagy (compulsion to swallow hair). When undiagnosed, gastric bezoars may cause gastric ulceration, perforation, haemorrhage and obstruction. CASE PRESENTATION: To underline the importance of including this pathology in the differential diagnosis of IDA and abdominal pain, we present the case of a 14 year-old girl with a huge trichobezoar which completely filled the stomach and extended into the small bowel. Since trichobezoar has an extension to the small bowel, it is classified as Rapunzel syndrome. As the bezoar couldn't be removed by endoscopy, the girl underwent surgical intervention. The patient passed through a gradual re-feeding, with iron and vitamins supplementation, and through a psychiatric counselling. CONCLUSION: The Rapunzel syndrome is a rare entity that may be complicated by life-threatening events. A prompt diagnosis and an appropriate therapy can reduce comorbidities. Gradual re-feeding with supplementation of micronutrients allows adequate catch-up weight with normalization of haematochemical nutritional parameters. Since many of these patients suffer from psychiatric pathology such as PICA with emotional problems and mental retardation, psychological/psychiatric counselling plays an important role in order to prevent bezoar recurrence.