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Summary: Haematopoietic stem cell reinjection may be a curative option for poor graft function after haematopoietic stem cell transplantation; however, literature supporting its use remains limited. We conducted a multicentre retrospective study on behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy, including 55 patients. We demonstrated response rates of nearly 40% and two‐year survival of more than 60% in the context of an otherwise deadly complication and we observed that the timing of injection and the degree of cytopenia are strongly associated with outcomes. This study shows the feasibility of the procedure informing on its epidemiology, outcomes and prognostic factors, setting the stage for future guidelines. [ABSTRACT FROM AUTHOR]

Background: Paediatric cutaneous granuloma with primary immunodeficiency (PID) is a rare condition. The physiopathology is unclear, and treatment is challenging. We report on 17 paediatric cases and review the literature. Objectives: To make dermatologists and dermatopathologists aware of the diagnostic value of skin granulomas in paediatric PID. Methods: We collected data on 17 patients with cutaneous granulomas and PID registered with us and also reviewed 33 cases from the literature. Results: Cutaneous granuloma was the presenting feature of the PID in 15 of the 50 collated cases. The lesions presented as red‐brownish nodules and infiltrated ulcerative plaques, predominantly on the face and limbs. Scleroderma‐like infiltration on a single limb was observed in 10% of the cases. The associated PID was ataxia‐telangiectasia (52%), combined immunodeficiency (24%), cartilage‐hair hypoplasia (6%) and other subtypes (18%). The granulomas were mostly sarcoidal, tuberculoid, palisaded or undefined subtypes. In some patients, several different histopathologic granulomatous patterns were found in the same biopsy. Some granulomas were associated with the presence of a vaccine strain of rubella virus. Conclusion: Cutaneous granulomas associated with a PID have a variable clinical presentation. A PID can be suspected when crusty, brownish lesions are found on the face or limbs. The concomitant presence of several histological subtypes in a single patient is suggestive of a PID. [ABSTRACT FROM AUTHOR]

A boy with X-linked agammaglobulinemia experienced progressive global motor decline, cerebellar syndrome, and epilepsy. All standard polymerase chain reactions for neurotropic viruses were negative on cerebrospinal fluid and brain biopsy. Next-generation sequencing allowed fast identification of a new astrovirus strain (HAstVVA1/HMO-C-PA), which led to tailor the patient's treatment, with encouraging clinical monitoring over 1 year. [ABSTRACT FROM AUTHOR]

Scarce data exist on allogeneic hematopoietic stem cell transplantation (HSCT) outcomes in hepatitis B virus (HBV)-naïve recipients from HBV-experienced donors. Long-term follow-up is herein reported for 17 allogeneic HSCT performed in 13 HBV-naïve children from HBc-antibodies-positive donors between 2006 and 2012. Four donors were HBs-antigen-positive, with detectable but low viremia in 2 cases (<2 logIU/ml). HBV-DNA was undetectable in all transplanted cell products. Recipients' HBV prophylaxis consisted of pre-transplant vaccination, polyvalent immune globulins, specific anti-HBV immune globulins, and/or oral lamivudine in 3, 12, 8, and 8 children, respectively. No case of HBV transmission occurred based on negative close monitoring of recipients' HBV serology and plasma HBV-DNA during a median follow-up of 22 months. In case of undetectable viremia in the donor, prophylaxis with vaccination and/or immune globulins in the recipient seems to be sufficient and lamivudine prophylaxis might be unnecessary to prevent viral transmission. In case of undetectable viremia in the donor, a systematic screening of HBV DNA in the stem cell product might be unnecessary to confirm the low risk of viral transmission. Prior exposure to HBV in the donor should not be considered a contraindication to HSCT. [ABSTRACT FROM AUTHOR]

Background: Identifying the molecular mechanisms of intrinsic aging is critical in developing modalities for reversal of cutaneous aging. Objective: The objective was to evaluate the expression of epidermal Fas, epidermal thickness, collagen, and elastic fibers degeneration in unexposed skin of aged individuals compared with young ones. Materials and Methods: Skin biopsies were taken from normal skin of the back of 22 old subjects (age range: 48-75 years) and 15 young subjects (age range: 18-28 years). Skin sections were stained with hematoxylin and eosin, Masson trichrome, orcein. Epidermal thickness was measured with image analyzer and scoring was done for collagen and elastic fiber degeneration. Fas immunostaining was done. Quantitative and qualitative data were compared statistically between the old and young subjects. Results: A statistically significant decreased epidermal thickness was found in old compared with young skin (P<0.05). A statistically significant number of patients showed decreased epidermal thickness, density, and fragmentation of both collagen and elastic fibers in old compared with young skin (P<0.001). Epidermal Fas expression was detected in 19 of 22 old subjects (86.4%) compared with 2 of 15 young subjects (13.3%) (P<0.001). There was no statistically significant correlation between age of old subjects and each of epidermal thickness, collagen, and elastic fiber degeneration. Conclusion: The decreased epidermal thickness and morphological alteration of collagen and elastic fibers are not correlated with aging and Fas-mediated apoptosis could be involved in thinning of the epidermis in unexposed aged skin. [ABSTRACT FROM AUTHOR]

Background Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare disorder characterized by neonatal autoimmune enteropathy, diabetes and thyroiditis, food allergies and skin rash. IPEX syndrome is caused by mutations in FOXP3, a master control gene of regulatory T cells (Tregs), resulting in absent or dysfunctional Tregs. Data in the literature are scarce and the cutaneous manifestations are rarely depicted. Objectives To evaluate the frequency and characteristics of cutaneous manifestations found in IPEX. Methods Retrospective single-centre study of a case series of IPEX. Patients’ data were retrieved from medical files and numerous parameters concerning general and cutaneous characteristics of the disease were recorded. Results Ten children with IPEX were studied. Cutaneous involvement was present in seven of 10 chidren; age at onset was 0–4 months, median 1·5. All patients presented with atopic dermatitis (AD). Three presented more psoriasiform lesions. Eczema was severe; most affected areas were lower limbs, trunk and face. Pruritus was present in four of seven, and painful fissurary cheilitis in four of seven. Hyper-IgE was found in seven of 10 and hypereosinophilia in five of 10. Skin biopsies showed eczematiform or psoriasiform features. Affected patients were improved by dermocorticoids; no clear improvement was obtained with immunosuppressive regimens. Other features were urticaria secondary to food allergies and staphylococcal sepsis, mostly Staphylococcus aureus and catheter related. Conclusions AD seems to be a frequent finding in IPEX syndrome, which is characterized by Treg anomalies. This hints to a possible role of Tregs in AD, which is then discussed in this study. [ABSTRACT FROM AUTHOR]

Oral busulfan clearance is age-dependent and children experience a wide variability in plasma exposure. BSA- or age-based dosing is used with therapeutic drug monitoring (TDM) to reduce this variability. A new intravenous (IV) dosing of busulfan (Bu) based on body weight, designed to improve AUC targeting without TDM and dose-adjustment, was prospectively evaluated. Bu was administered as a 2 h IV infusion every 6 h over 4 days (16 administrations). Five dose levels were defined on body weight as follows: 1.0 mg/kg for <9 kg; 1.2 mg/kg for 9 to <16 kg; 1.1 mg/kg for 16–23 kg; 0.95 mg/kg for >23–34 kg; 0.80 mg/kg for >34 kg. Bu treatment was followed by Cyclophosphamide or Melphalan prior to allogeneic or autologous transplantation in 55 children aged 0.3–17.2 years (median 5.6 years). No difference in AUC values was observed between weight strata (mean ± SD 1248 ± 205 μmol·min), whereas a significant difference in Bu clearance was demonstrated. This new dosing enabled to achieve a mean exposure comparable to that in adults. At dose 1, 91% of patients achieved the targeted AUC range (900–1500 μmol·min) while no patients were underexposed. At doses 9 and 13, over 75% of patients remained within that target whilst most of the others were slightly above. Successful engraftment was achieved in all patients. In conclusion, from infants to adults this new dosing enabled, without TDM and dose adjustment, to successfully target a therapeutic AUC window. [ABSTRACT FROM AUTHOR]

Oral busulfan clearance is age-dependent and children experience a wide variability in plasma exposure. BSA- or age-based dosing is used with therapeutic drug monitoring (TDM) to reduce this variability. A new intravenous (IV) dosing of busulfan (Bu) based on body weight, designed to improve AUC targeting without TDM and dose-adjustment, was prospectively evaluated. Bu was administered as a 2 h IV infusion every 6 h over 4 days (16 administrations). Five dose levels were defined on body weight as follows: 1.0 mg/kg for <9 kg; 1.2 mg/kg for 9 to <16 kg; 1.1 mg/kg for 16–23 kg; 0.95 mg/kg for >23–34 kg; 0.80 mg/kg for >34 kg. Bu treatment was followed by Cyclophosphamide or Melphalan prior to allogeneic or autologous transplantation in 55 children aged 0.3–17.2 years (median 5.6 years). No difference in AUC values was observed between weight strata (mean ± SD 1248 ± 205 μmol·min), whereas a significant difference in Bu clearance was demonstrated. This new dosing enabled to achieve a mean exposure comparable to that in adults. At dose 1, 91% of patients achieved the targeted AUC range (900–1500 μmol·min) while no patients were underexposed. At doses 9 and 13, over 75% of patients remained within that target whilst most of the others were slightly above. Successful engraftment was achieved in all patients. In conclusion, from infants to adults this new dosing enabled, without TDM and dose adjustment, to successfully target a therapeutic AUC window. [ABSTRACT FROM AUTHOR]

Adenovirus infections result in significant morbidity and mortality in allogeneic haematopoietic stem cell transplanted (hSCT) children. Adenovirus from species C and B account for more than 90% of adenoviruses recovered after hSCT. However, infections due to adenovirus A31 have been increasingly reported in recent years. Between April 2002 and April 2005, blood samples obtained every 2 weeks from 58 hSCT children were screened for adenovirus species A to C by quantitative real-time PCR. Phylogenetic analysis was realized after amplification and sequencing of the entire hexon gene. Fifteen cases of adenovirus infection with viraemia were recovered during this 3 years period. During spring/summer 2003, seven cases occurred and were due to an adenovirus species A. Phylogenetic analysis of the seven strains showed that they belonged to the A31 genotype and shared 100% homology. Clinical features of the seven HSCT children with A31 adenovirus viraemia are described. We describe here an epidemic spread of adenovirus genotype A31 in a paediatric haematology unit. Timing, location and hexon gene genotyping results highly suggested a nosocomial origin to this epidemic. The burden of adenovirus A31 infection needs to be further assessed in this context.Bone Marrow Transplantation (2006) 38, 23–28. doi:10.1038/sj.bmt.1705389; published online 15 May 2006 [ABSTRACT FROM AUTHOR]

The article presents a study which investigates the toxicity of dimethoate to two freshwater fishes such as guppy Poecilia reticulate and zebrafish Brachydanio rerio and Daphnia magna Straus. The recommended guidelines from the Commission of the European Communities was used to examine the acute toxicity tests of freshwater fishes and daphnids. The results reveal that the 10% emulsible concentration of insecticide dimethoate is more toxic to the two freshwater fishes and D. magna.

The article discusses the study on the toxicological effects of vanadium to various freshwater organisms. The experiments were conducted using different methods such as ultraviolet-visible (UV-VIS) spectrophotometer, bubble-aeration and toxicity tests. Results show that zebrafish are more susceptible to vanadium than guppy while mortality did not go over 10% during the chronic testing.

An abstract of the conference paper "Diversity in clinical manifestations of autoinflammatory syndromes," by S. Boiuand and colleagues is presented.

An abstract of the conference paper "The Eurofever Registry for autoinflammatory diseases: results of the first 15 months of enrolment," by N. Toplak and colleagues is presented.