Genotype-Phenotype Relationships in Inheritable Idiopathic Pulmonary Fibrosis: A Greek National Cohort Study.

Background: Monogenic and polygenic inheritances are evidenced for idiopathic pulmonary fibrosis (IPF). Pathogenic variations in surfactant protein-related genes, telomere-related genes (TRGs), and a single-nucleotide polymorphism in the promoter of MUC5B gene encoding mucin 5B (rs35705950 T risk allele) are reported. This French-Greek collaborative study, Gen-Phen-Re-GreekS in inheritable IPF (iIPF), aimed to investigate genetic components and patients' characteristics in the Greek national IPF cohort with suspected heritability.

A Novel Heterozygous Deletion Variant in Gene Leading to Haploinsufficiency and Impairment of Fibroblast Growth Factor 23 Signaling Pathway.

Hyperphosphatemia is commonly present in end-stage renal disease. Klotho (KL) is implicated in phosphate homeostasis since it acts as obligate co-receptor for the fibroblast growth factor 23 (FGF23), a major phosphaturic hormone. We hypothesized that genetic variation in the KL gene might be associated with alterations in phosphate homeostasis resulting in hyperphosphatemia.

Lipodystrophy-like features after total body irradiation among survivors of childhood acute leukemia.

Background/objective: The number of long-term survivors of childhood acute leukemia (AL) is substantially growing. These patients are at high risk for metabolic syndrome (MS), especially those who received total body irradiation (TBI). The consequences of children's irradiation on adipose tissue (AT) development in adulthood are currently unknown.

The R178Q mutation is a recurrent cause of hemochromatosis and is associated with a novel pathogenic mechanism.

Hemochromatosis type 4 is one of the most common causes of primary iron overload, after -related hemochromatosis. It is an autosomal dominant disorder, primarily due to missense mutations in This gene encodes ferroportin 1 (FPN1), which is the sole iron export protein reported in mammals. Not all heterozygous missense mutations in are disease-causing.

Prevalence and characteristics of metabolic syndrome in adults from the French childhood leukemia survivors' cohort: a comparison with controls from the French population.

The prevalence of the metabolic syndrome among adults from the French LEA childhood acute leukemia survivors' cohort was prospectively evaluated considering the type of anti-leukemic treatment received, and compared with that of controls. The metabolic profile of these patients was compared with that of controls. A total of 3203 patients from a French volunteer cohort were age- and sex-matched 3:1 to 1025 leukemia survivors (in both cohorts, mean age: 24.

Surveillance of carbapenemase-producing Enterobacteriaceae in the Indian Ocean Region between January 2010 and December 2015.

Background: The aim of this study was to trace the emergence of carbapenemase-producing Enterobacteriaceae (CPE) on Reunion Island, a French overseas territory well suited for the surveillance of CPE emergence in patients from the entire Indian Ocean Region.

Methods: This retrospective multicenter study was conducted on Reunion Island between 2010 and 2015.

Results: A total of 43 CPEs were isolated during the course of the study, in 36 patients (50% in the last year alone).

Cytogenetics and outcome of allogeneic transplantation in first remission of acute myeloid leukemia: the French pediatric experience.

We analyzed the impact of cytogenetics on 193 children enrolled in two successive French trials (LAME89/91 and ELAM02), who received hematopoietic stem cell transplantation during CR1. Detailed karyotype was available for 66/74 (89%) in LAME89/91 and 118/119 (99%) in ELAM02. Several karyotype and transplant characteristics differed according to therapeutic protocol: unfavorable karyotypes were more frequent in ELAM02 (36% vs 18%), pretransplant chemotherapy included high-dose cytarabine in ELAM02 and not in LAME89/91, IV replaced oral busulfan in the conditioning regimen, methotrexate was removed from post-transplant immunosuppression, and matched unrelated donor and cord blood transplantation were introduced.

Prevalence and risk factors of iron overload after hematopoietic stem cell transplantation for childhood acute leukemia: a LEA study.

Data on post-transplant iron overload (IO) are scarce in pediatrics. We conducted a prospective multicenter cohort study (Leucémie de l'Enfant et de l'Adolescent cohort) to determine the prevalence and risk factors of IO in 384 acute leukemia survivors transplanted during childhood. Prevalence of IO (ferritin level ⩾350 ng/mL) was 42.

The Impact of Donor Type on Long-Term Health Status and Quality of Life after Allogeneic Hematopoietic Stem Cell Transplantation for Childhood Acute Leukemia: A Leucémie de l'Enfant et de L'Adolescent Study.

We compared the long-term impact of donor type (sibling donor [SD] versus matched unrelated donor [MUD] or umbilical cord blood [UCB]) on late side effects and quality of life (QoL) in childhood acute leukemia survivors treated with hematopoietic stem cell transplantation. We included 314 patients who underwent transplantation from 1997 to 2012 and were enrolled in the multicenter French Leucémie de l'Enfant et de L'Adolescent ("Leukemia in Children and Adolescents") cohort. More than one-third of the patients were adults at last visit; mean follow-up duration was 6.

Metabolic syndrome in long-term survivors of childhood acute leukemia treated without hematopoietic stem cell transplantation: an L.E.A. study.

Cardiovascular conditions are serious long-term complications of childhood acute leukemia. However, few studies have investigated the risk of metabolic syndrome, a known predictor of cardiovascular disease, in patients treated without hematopoietic stem cell transplantation. We describe the overall and age-specific prevalence, and the risk factors for metabolic syndrome and its components in the L.

Single- vs double-unit cord blood transplantation for children and young adults with acute leukemia or myelodysplastic syndrome.

Transplantation of 2 unrelated cord blood (UCB) units instead of 1 has been proposed to increase the cell dose. We report a prospective randomized study, designed to compare single- vs double-UCB transplantation in children and young adults with acute leukemia in remission or myelodysplasia. Eligible patients had at least two 4-6 HLA-identical UCBs with >3 × 10(7) nucleated cells/kg for the first and >1.

Late thyroid complications in survivors of childhood acute leukemia. An L.E.A. study.

Thyroid complications are known side effects of irradiation. However, the risk of such complications in childhood acute leukemia survivors who received either central nervous system irradiation or hematopoietic stem cell transplantation is less described. We prospectively evaluated the incidence and risk factors for thyroid dysfunction and tumors in survivors of childhood acute myeloid or lymphoid leukemia.

Heterozygous Mutations in BMP6 Pro-peptide Lead to Inappropriate Hepcidin Synthesis and Moderate Iron Overload in Humans.

Background & Aims: Hereditary hemochromatosis is a heterogeneous group of genetic disorders characterized by parenchymal iron overload. It is caused by defective expression of liver hepcidin, the main regulator of iron homeostasis. Iron stimulates the gene encoding hepcidin (HAMP) via the bone morphogenetic protein (BMP)6 signaling to SMAD.

Metabolic syndrome in adults who received hematopoietic stem cell transplantation for acute childhood leukemia: an LEA study.

We evaluated prospectively the incidence and risk factors of the metabolic syndrome (MS) and its components in 170 adult patients (mean age at evaluation: 24.8±5.4 years) who received an hematopoietic stem cell transplantation for childhood ALL, n=119, or AML, n=51.

Quality of life in minor siblings of childhood leukemia survivors, long-term after diagnosis: A LEA study (for Leucemies de l'Enfant et de l'Adolescent--childhood and adolescent leukemia).

Objective: The objectives of this study are to assess the quality of life (QoL) of siblings of childhood leukemia survivors in comparison with population controls and to identify determinants of sibling's QoL.

Methods: The nearest-aged siblings (8-17 years) of minor CLS participating in the French LEA cohort (Childhood and Adolescent Leukemia), at the Marseilles center, were included. Siblings' QoL was self-reported using the 'Vécu et Santé Perçue de l'Adolescent et l'enfant' questionnaire.

Incidence and risk factors for cataract after haematopoietic stem cell transplantation for childhood leukaemia: an LEA study.

Cataract was prospectively assessed by serial slip lamp tests in 271 patients included in the Leucémie Enfants Adolescents (LEA) programme, the French cohort of childhood leukaemia survivors. All had received haematopoietic stem cell transplantation (HSCT) after total body irradiation (TBI, n = 201) or busulfan-based (n = 70) myeloablative conditioning regimen. TBI was fractionated in all but six patients.

Functional and clinical impact of novel TMPRSS6 variants in iron-refractory iron-deficiency anemia patients and genotype-phenotype studies.

Iron-refractory iron-deficiency anemia (IRIDA) is a rare autosomal-recessive disorder characterized by hypochromic microcytic anemia, low transferrin saturation, and inappropriate high levels of the iron hormone hepcidin. The disease is caused by variants in the transmembrane protease serine 6 (TMPRSS6) gene that encodes the type II serine protease matriptase-2, a negative regulator of hepcidin transcription. Sequencing analysis of the TMPRSS6 gene in 21 new IRIDA patients from 16 families with different ethnic origin reveal 17 novel mutations, including the most frequent mutation in Southern Italy (p.

Reduced-toxicity conditioning prior to allogeneic stem cell transplantation improves outcome in patients with myeloid malignancies.

The introduction of reduced intensity/toxicity conditioning regimens has allowed allogeneic hematopoietic cell transplantation to be performed in patients who were previously considered too old or otherwise unfit. Although it led to a reduction in non-relapse mortality, disease control remains a major challenge. We studied the outcome of 165 patients with acute myeloid leukemia (n=124) or myelodysplastic syndrome (n=41) transplanted after conditioning with fludarabine (30 mg/m(2)/day for 5 days), intravenous busulfan (either 260 mg/m(2): reduced intensity conditioning, or 390-520 mg/m(2): reduced toxicity conditioning), and rabbit anti-thymoglobulin (2.