Vitamin D status and predictors of hypovitaminosis D in internationally adopted children

To evaluate vitamin D status in internationally adopted children at first medical evaluation in Italy and to identify possible risk factors for hypovitaminosis D in this population.25-hydroxyvitamin D [25(OH)D] levels were analyzed in internationally adopted children consecutively recruited at one Italian Center between 2010 and 2014 as part of the first screening protocol. Demographic, clinical and laboratory data were prospectively collected. Serum 25(OH)D levels <10 ng/mL, <20 ng/mL, and <30 ng/mL were used to define severe vitamin D deficiency, vitamin D deficiency and hypovitaminosis D, respectively.962 internationally adopted children (median age: 5.47 years; IQR:3.14-7.93) were included in the study. Median 25(OH)D level was 22.0 ng/mL (IQR:15.0-30.0 ng/mL); 710/962 (73.8%) children showed hypovitaminosis D (<30 ng/mL), 388/962 (40.3%) had vitamin D deficiency (<20 ng/dL), and 92/962 (9.6%) had severe vitamin D deficiency (<10ng/mL). No case of clinical rickets was observed. Hypovitaminosis D was particularly frequent (>90%) in children adopted from Ethiopia, Peru, India, Bulgaria and Lithuania. At multivariate analysis an increased risk of hypovitaminosis D was found to be associated with: age ≥ 6 years, time spent in Italy ≥ 3 months, blood sample taken in winter, spring or fall, compared to summer. Gender, ethnicity/continent of origin, tubercular infection, intestinal parassitosis and BMI-z-score < -2 were not associated with vitamin D status.Hypovitaminosis D is common in internationally adopted children, from all ethnic group. The evaluation of serum 25(OH)D level could be useful early after the adoption to promptly start vitamin D supplementation/treatment if needed

Infectious diseases prevalence, vaccination coverage, and diagnostic challenges in a population of internationally adopted children referred to a Tertiary Care Children&apos;s Hospital from 2009 to 2015

Infectious diseases are common in internationally adopted children (IAC). With the objective to evaluate infectious diseases prevalence in a large cohort of IAC and to explore possible risk factors for tuberculosis (TB) and parasitic infections, clinical and laboratory data at first screening visit of all IAC (<18 years) consecutively referred to our Center in 2009 to 2015 were collected and analyzed. In total, 1612 children (median age: 5.40 years; interquartile range: 3.00–7.90) were enrolled, 123/1612 (7.60%) having medical conditions included in the special needs definition. The most frequent cutaneous infections were Molluscum contagiosum (42/1612; 2.60%) and Tinea capitis (37/1612; 2.30%). Viral hepatitis prevalence was <1% (hepatitis B virus [HBV]: 13 children, 0.80%; hepatitis C virus: 1 child, 0.10%; hepatitis A virus: 6 children, 0.40%). A parasitic infection was diagnosed in 372/1612 (23.10%) children. No risk factors for parasitosis were evidenced. Active TB was diagnosed in 4/1355 (0.3%) children, latent TB in 222/1355 (16.40%). Only 3.7% (51/1355) children had concordant positive tuberculin skin test (TST) and QuantiFERON-TB-Gold In-Tube (QFT-G-IT) results. Risk factors for TST+/QFT-G-IT− results were previous Bacille de Calmette-Guérin vaccination (adjusted odds ratio [aOR]: 2.18; 96% confidence interval [CI]: 1.26–3.79; P = 0.006), and age ≥5 years (aOR: 1.49; 95% CI: 1.06–2.11; P = 0.02). The proportion of children with nonprotective titers for vaccine-preventable diseases (VPD) ranged from 15.70% (208/1323) for tetanus to 35.10% (469/1337) for HBV. Infectious diseases were commonly observed in our cohort. The high rate of discordant TST/QFT-G results brings up questions regarding the optimal management of these children, and suggests that, at least in children older than 5 years, only QFT-G-IT results may be reliable. The low proportion of children protected for VPD, confirms importance of a timely screening

Idiopathic thrombocytopenic purpura and coronary artery disease: comparison between coronary artery bypass grafting and percutaneous coronary intervention.

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by a low platelet count and an increased risk of bleeding. At the same time, ITP patients present an increased risk of thrombosis and atherosclerosis related to the high presence of haemostatic factors and chronic steroid therapy. Although relatively rare, the association of ITP and coronary artery disease represents a complex therapeutic challenge. In particular, no recommendations exist regarding the best management approach. We reviewed the literature making a comparison between coronary artery bypass grafting and percutaneous coronary intervention. © 2011 Published by European Association for Cardio-Thoracic Surgery. All rights reserved

Variable Phenotype in a P102L Gerstmann-Sträussler-Scheinker Italian Family

Background:Gerstmann-Sträussler-Scheinker disease is an autosomal dominant prion disease. The clinical features include ataxia, dementia, spastic paraparesis and extrapyramidal signs.Methods:We report a new large Italian family affected by Gerstmann-Sträussler-Scheinker disease.Results:The four generation pedigree includes 11 patients. The mean age at onset ± SD was 41.4 ± 16.2 years. Mean disease duration to death in four patients was 5.5 ± 1.7 years. Two clinical patterns were evident: cognitive impairment with scarce neurological features or ataxia followed by cognitive impairment. Molecular analysis showed P102L mutation in PRNP gene.Conclusion:Three Italian families have been reported to date. The variable phenotype has already been reported, and does not appear related to the codon 129 polymorphism

Detection of TDP-43 seeding activity in the olfactory mucosa from patients with frontotemporal dementia

INTRODUCTION: We assessed TAR DNA-binding protein 43 (TDP-43) seeding activity and aggregates detection in olfactory mucosa of patients with frontotemporal lobar degeneration with TDP-43-immunoreactive pathology (FTLD-TDP) by TDP-43 seeding amplification assay (TDP43-SAA) and immunocytochemical analysis. METHODS: The TDP43-SAA was optimized using frontal cortex samples from 16 post mortem cases with FTLD-TDP, FTLD with tau inclusions, and controls. Subsequently, olfactory mucosa samples were collected from 17 patients with FTLD-TDP, 15 healthy controls, and three patients carrying MAPT variants. RESULTS: TDP43-SAA discriminated with 100% accuracy post mortem cases presenting or lacking TDP-43 neuropathology. TDP-43 seeding activity was detectable in the olfactory mucosa, and 82.4% of patients with FTLD-TDP tested positive, whereas 86.7% of controls tested negative (P < 0.001). Two out of three patients with MAPT mutations tested negative. In TDP43-SAA positive samples, cytoplasmatic deposits of phosphorylated TDP-43 in the olfactory neural cells were detected. DISCUSSION: TDP-43 aggregates can be detectable in olfactory mucosa, suggesting that TDP43-SAA might be useful for identifying and monitoring FTLD-TDP in living patients

Detection of TDP-43 seeding activity in the olfactory mucosa from patients with frontotemporal dementia

Introduction: We assessed TAR DNA-binding protein 43 (TDP-43) seeding activity and aggregates detection in olfactory mucosa of patients with frontotemporal lobar degeneration with TDP-43-immunoreactive pathology (FTLD-TDP) by TDP-43 seeding amplification assay (TDP43-SAA) and immunocytochemical analysis. Methods: The TDP43-SAA was optimized using frontal cortex samples from 16 post mortem cases with FTLD-TDP, FTLD with tau inclusions, and controls. Subsequently, olfactory mucosa samples were collected from 17 patients with FTLD-TDP, 15 healthy controls, and three patients carrying MAPT variants. Results: TDP43-SAA discriminated with 100% accuracy post mortem cases presenting or lacking TDP-43 neuropathology. TDP-43 seeding activity was detectable in the olfactory mucosa, and 82.4% of patients with FTLD-TDP tested positive, whereas 86.7% of controls tested negative (P&nbsp;&lt;&nbsp;0.001). Two out of three patients with MAPT mutations tested negative. In TDP43-SAA positive samples, cytoplasmatic deposits of phosphorylated TDP-43 in the olfactory neural cells were detected. Discussion: TDP-43 aggregates can be detectable in olfactory mucosa, suggesting that TDP43-SAA might be useful for identifying and monitoring FTLD-TDP in living patients

Reduced Mortality With Antiplatelet Therapy Deescalation After Percutaneous Coronary Intervention in Acute Coronary Syndromes: A Meta-Analysis

Background:Antiplatelet therapy deescalation has been suggested as an alternative to standard treatment with potent dual antiplatelet therapy (DAPT) for 1 year in low bleeding risk patients with acute coronary syndromes undergoing percutaneous coronary intervention to mitigate the increased risk of bleeding. Whether this strategy preserves the ischemic and survival benefits of potent DAPT is uncertain. Methods:We performed a pairwise meta-analysis in patients with acute coronary syndrome undergoing percutaneous coronary intervention treated with either 1-year standard potent DAPT versus deescalation therapy (potent DAPT for 1-3 months followed by either reduced potency DAPT or ticagrelor monotherapy for up to 1 year). Randomized trials comparing standard DAPT versus deescalation therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention were searched through MEDLINE, EMBASE, Cochrane databases, and proceedings of international meetings. The primary end point was 1-year all-cause mortality. Results:The meta-analysis included 6 trials in which 20 837 patients were randomized to potent DAPT for 1 to 3 months followed by deescalation therapy for up to 1 year (n=10 392) or standard potent DAPT for 1 year (n=10 445). Deescalation therapy was associated with lower 1-year rates of all-cause mortality compared with standard therapy (odds ratio, 0.75 [95% CI, 0.59-0.95]; P=0.02). Deescalation therapy was also associated with lower rates of major bleeding (odds ratio, 0.59 [95% CI, 0.48-0.72]; P<0.0001), with no significant difference in major adverse cardiac events (major adverse cardiovascular events; odds ratio, 0.89 [95% CI, 0.77-1.04]; P=0.14). Conclusions:In low bleeding risk patients with acute coronary syndrome undergoing percutaneous coronary intervention, compared with 1-year of potent DAPT, antiplatelet therapy deescalation therapy after 1 to 3 months was associated with decreased mortality and major bleeding with similar rates of major adverse cardiovascular events

Novel and Rare Fusion Transcripts Involving Transcription Factors and Tumor Suppressor Genes in Acute Myeloid Leukemia.

Approximately 18% of acute myeloid leukemia (AML) cases express a fusion transcript. However, few fusions are recurrent across AML and the identification of these rare chimeras is of interest to characterize AML patients. Here, we studied the transcriptome of 8 adult AML patients with poorly described chromosomal translocation(s), with the aim of identifying novel and rare fusion transcripts. We integrated RNA-sequencing data with multiple approaches including computational analysis, Sanger sequencing, fluorescence in situ hybridization and in vitro studies to assess the oncogenic potential of the ZEB2-BCL11B chimera. We detected 7 different fusions with partner genes involving transcription factors (OAZ-MAFK, ZEB2-BCL11B), tumor suppressors (SAV1-GYPB, PUF60-TYW1, CNOT2-WT1) and rearrangements associated with the loss of NF1 (CPD-PXT1, UTP6-CRLF3). Notably, ZEB2-BCL11B rearrangements co-occurred with FLT3 mutations and were associated with a poorly differentiated or mixed phenotype leukemia. Although the fusion alone did not transform murine c-Kit+ bone marrow cells, 45.4% of 14q32 non-rearranged AML cases were also BCL11B-positive, suggesting a more general and complex mechanism of leukemogenesis associated with BCL11B expression. Overall, by combining different approaches, we described rare fusion events contributing to the complexity of AML and we linked the expression of some chimeras to genomic alterations hitting known genes in AML

Decellularized human dermal matrix produced by a skin bank: A new treatment for abdominal wall defects

BACKGROUND; Interest is increasing for human decellularized scaffolds for their ability to favor healing and cell infiltration after transplantation, in the treatment of abdominal wall defects. The purpose of the present study is to show the clinical results obtained after the application of human decellularized dermal matrix (HDM) produced by RER Skin Bank, on patients suffering from different abdominal wall defects. METHODS: Between 2012 and 2014, 64 patients, average age 64 years, received HDM, to replace and cover the damage area during abdominal wall surgery. After surgical procedures, all patients were followed weekly for the first month and then monthly up to 6 months postoperative and any major problem or complication were recorded. Six months follow up included abdominal exams, serological tests and MRI analysis in order to evaluate integration of HDM with the patients surroundings tissues and eventual long-term complications. RESULTS: Incisional hernia was the most frequent clinical condition in which HDM was applied, requiring also the highest amount of human decellularized dermal matrix. One month after the surgical operation, 61 patients revealed a well tolerability of HDM and a normal wound healing was also identified in all the damage areas. Only 3 patients experienced postoperative infections. Moreover the follow up after 6 months reported no signs of dermis rejection and that none of the patients was positive to serological tests. CONCLUSIONS: Human decellularized dermal matrix can be considered a safe and useful bioproduct to treat large abdominal defects, characterized by minor complications and simplicity to be implanted