Cutaneous Disease in Autism Spectrum Disorder: A Review

Dermatologic comorbid symptoms and conditions in persons with autism spectrum disorder (ASD) are compelling for several reasons, including problems with tactile sensory dysfunction in this population, a large number of syndromes with dermatologic findings and high rates of autism, nutritional and hormonal problems in ASD and their dermatologic manifestations, and the potential for overrepresentation of dermatologic symptoms that are neurobehavioral in nature. The current article reviews the available literature on the prevalence of comorbid dermatologic symptoms and conditions in children with ASD and identifies strategies for diagnosing and managing cutaneous disease in this population.     

Long-term survival of ex-thalassemic patients with persistent mixed chimerism after bone marrow transplantation

Twenty-six transplanted thalassemic patients out of 295 analyzed, showed the presence of persistent mixed chimerism, over a period of time varying between 2 and 11 years after BMT. Despite the presence of large numbers of residual host cells, these transplanted thalassemic patients no longer require red blood cell transfusions and have a functional graft, producing sufficient levels of hemoglobin A ranging from 8.3-14.7 g/dl. These ex-thalassemic patients with persistent mixed chimerism, although they did not achieve complete donor engraftment are no longer exposed to the risk of graft rejection. The mechanisms underlying this apparent state of tolerance or education in these patients are at the present time unknown. However, these observations may be useful for physicians involved in defining optimal strategies for clinical gene therapy, in utero hematopoietic stem cell transplantation and adoption of less toxic conditioning regimens in mini-transplantation.     

Transplantation of fetal liver of different ages in the rat

Summary This study investigates the effect of fetal liver transplantation in reconstituting hemopoiesis in supralethally irradiated rats. Different cell doses of fetuses at the embryonic age of 15 and 18 days were compared to equivalent cell doses of adult bone marrow cells. Although the frequency of engraftment ranged between 75 and 100% in all the groups of animals studied, the survival rate at 30 days after TBI did not show any significant difference between the fetal liver and the bone marrow treated recipients. The bone marrow transplants performed in littermate rats almost doubled the percentage of survivors at 30 days and showed a cell dose relationship suggesting that, in the closed colony of random-bred rats used, the mortality after bone marrow and fetal liver transplants was mainly due to graft-versus-host-disease. Antibiotic prophylaxis and treatment during the experiment did not modify the results in a separate group of fetal liver and bone marrow transplanted rats. In the rat model system used in this set of experiments fetal liver did not reveal any advantage over bone marrow transplantation.Supported by CNR N 80.00486 Rome, Italy, and Stiftung Volkswagenwerk Hannover, Federal Republic of Germany     

Evaluation of cardiac status in iron-loaded thalassaemia patients following bone marrow transplantation: improvement in cardiac function during reduction in body iron burden

Iron-induced cardiac disease is the primary cause of death in transfused patients with thalassaemia major. The beneficial effects of deferoxamine mesylate on clinical cardiac disease have been well described but the impact of therapy on subclinical cardiac dysfunction is unknown. To assess the reversibility of subclinical cardiac dysfunction we studied the cardiac status during iron depletion treatment (phlebotomy) in iron overloaded patients, cured of thalassaemia by marrow transplantation, without clinical manifestation of heart failure but with alteration in both left ventricular diastolic function and in contractility property. 32 patients were studied and demonstrated a slight but significant impairment in the morphology and function if compared with matched normal controls. 17 of these patients were submitted to sequential echocardiographic evaluations during the phlebotomy programme. Following completion of the programme, normalization of the indices of contractility and normalization of diastolic function were observed. This study indicates that transplanted thalassaemia patients with subclinical left ventricular diastolic dysfunction and impaired left ventricular contractility may reverse these processes with an effective regimen of iron reduction such as phlebotomy.     

Haematopoietic stem cell transplantation in Nigerian sickle cell anaemia children patients

Background:

Sickle cell anaemia (SCA) remains associated with high risks of morbidity and early death. Children with SCA are at high risk for ischaemic stroke and transient ischaemic attacks, secondary to intracranial arteriopathy involving carotid and cerebral arteries. Allogeneic haematopoietic stem cell transplantation (HSCT) is the only curative treatment for SCA. We report our experience with transplantation in a group of patients with the Black African variant of SCA.

Patients and Methods:

This study included 31 consecutive SCA patients who underwent bone marrow transplantation from human leukocyte antigen (HLA)-identical sibling donors between 2010 and 2014 following a myeloablative-conditioning regimen.

Results:

The median patient age was 10 years (range 2–17 years). Before transplantation, 14 patients had recurrent, painful, vaso-occlusive crisis; ten patients had recurrent painful crisis in association with acute chest syndrome; three patients experienced ischaemic stroke and recurrent vaso-occlusive crisis; two patients experienced ischaemic stroke; one patient exhibited leukocytosis; and one patient exhibited priapism. Of the 31 patients, 28 survived without sickle cell disease, with Lansky/Karnofsky scores of 100. All surviving patients remained free of any SCA-related events after transplantation.

Conclusion:

The protocols used for the preparation to the transplant in thalassaemia are very effective also in the other severe haemoglobinopathy as in the sickle cell anaemia with 90% disease free survival. Today, if a SCA patient has a HLA identical family member, the cellular gene therapy through the transplantation of the allogeneic haemopoietic cell should be performed. Tomorrow, hopefully, the autologous genetically corrected stem cell will break down the wall of the immunological incompatibility.     

Drain After Laparoscopic Cholecystectomy for Acute Calculous Cholecystitis. A Pilot Randomized Study

Drainage after laparoscopic cholecystectomy (LC) for acute calculous cholecystitis (ACC) is used without evidence of its efficacy. The present pilot study was designed to address this issue. After laparoscopic gallbladder removal, 15 patients were randomized to have a drain positioned in the subhepatic space (group A) and 15 patients to have a sham drain (group B). The primary outcome measure was the presence of subhepatic fluid collection at abdominal ultrasonography, performed 24 h after surgery. Secondary outcome measures included postoperative abdominal and shoulder tip pain, use of analgesics, and morbidity. Abdominal ultrasonography did not show any subhepatic fluid collection in eight patients (53.3 %) in group A and in five patients (33.3 %) in group B (P?=?0.462). If present, median (range) subhepatic collection was 50 mL (20–100 mL) in group A and 80 mL (30–120 mL) in group B (P?=?0.573). No significant differences in the severity of abdominal and shoulder pain and use of parenteral ketorolac were found in either group. Two biliary leaks and one subhepatic fluid collection occurred postoperatively. The present study was unable to prove that the drain was useful in LC for ACC, performed in a selected group of patients.     

Risk of type 1 diabetes in childhood and maternal age at delivery, interaction with ACP1 and sex

BACKGROUND: We have investigated the possible role of ACP1 (also known as cLMWPTP: cytosolic low molecular weight phosphotyrosine phosphatase), a highly polymorphic enzyme involved in signal transduction of T-cell receptor, insulin receptor and other growth factors in the relationship between maternal age at delivery and risk of type 1 diabetes in the offspring. METHODS: One hundred and eighty-nine consecutive children with type 1 diabetes (TIDM) diagnosed at the Department of Pediatrics of the University of Sassari (Sardinia) were studied. A control sample of 5460 consecutive newborns from the same population was also studied. RESULTS: Maternal age at birth of children with type 1 diabetes has shifted towards high values. There is also an effect of birth order on the susceptibility to type 1 diabetes, which is independent of that due to maternal age. The proportion of low activity ACPl genotypes is much higher among children born from older mothers than among diabetic children born from relatively young mothers. There is a significant effect of sex, maternal age, sex-ACPl two-way interaction and sex-ACP1-maternal age three-way interaction on the age at diagnosis of diabetes. CONCLUSIONS: The present data confirm the strong association between maternal age at delivery and risk of type 1 diabetes in the child. In addition, our analysis suggests a complex interaction among maternal age, sex of infant and ACP1 concerning age at diagnosis of diabetes. Thus, risk and clinical course of type 1 diabetes seem to be dependent on both maternal environment during intrauterine development and foetal genetic factors.     

Evaluating the clinical accuracy of GlucoMen®Day: a novel microdialysis-based continuous glucose monitor

Background

The objective of this work was to determine the clinical accuracy of GlucoMen®Day, a new microdialysis-based continuous glucose monitoring system (CGMS) from A. Menarini Diagnostics (Florence, Italy). Accuracy evaluation was performed using continuous glucose-error grid analysis (CG-EGA), as recommended by the Performance Metrics for Continuous Interstitial Glucose Monitoring; Approved Guideline (POCT05-A).

Methods

Two independent clinical trials were carried out on patients with types 1 and 2 diabetes mellitus, the glycemic levels of whom were monitored in an in-home setting for 100-hour periods. A new multiparametric algorithm was developed and used to compensate in real-time the GlucoMen®Day signal.The time lag between continuous glucose monitoring (CGM) and reference data was first estimated using the Poincaré plot method. The entire set of CGM/reference data pairs was then evaluated following the CG-EGA criteria, which allowed an estimation of the combined point and rate accuracy stratified by glycemic ranges.

Results

With an estimated time lag of 11 minutes, the linear regression analysis of the CGM/reference glucose values yielded r = 0.92. The mean absolute error (MAE) was 11.4 mg/dl. The calculated mean absolute rate deviation (MARD) was 0.63 mg/dl/min. The data points falling within the A+B zones of CG-EGA were 100% in hypoglycemia, 95.7% in euglycemia, and 95.2% in hyperglycemia.

Conclusions

The GlucoMen®Day system provided reliable, real-time measurement of subcutaneous glucose levels in patients with diabetes for up to 100 hours. The device showed the ability to follow rapid glycemic excursions and detect severe hypoglycemic events accurately. Its accuracy parameters fitted the criteria of the state-of-the-art consensus guideline for CGMS, with highly consistent results from two independent studies.