Beckwith–Wiedemann syndrome (BWS), a human genomic imprinting disorder, is characterized by phenotypic variability that might include overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycaemia, lateralized overgrowth and predisposition to embryonal tumours. Delineation of the molecular defects within the imprinted 11p15.5 region can predict familial recurrence risks and the risk (and type) of embryonal tumour. Despite recent advances in knowledge, there is marked heterogeneity in clinical diagnostic criteria and care. As detailed in this Consensus Statement, an international consensus group agreed upon 72 recommendations for the clinical and molecular diagnosis and management of BWS, including comprehensive protocols for the molecular investigation, care and treatment of patients from the prenatal period to adulthood. The consensus recommendations apply to patients with Beckwith–Wiedemann spectrum (BWSp), covering classical BWS without a molecular diagnosis and BWS-related phenotypes with an 11p15.5 molecular anomaly. Although the consensus group recommends a tumour surveillance programme targeted by molecular subgroups, surveillance might differ according to the local health-care system (for example, in the United States), and the results of targeted and universal surveillance should be evaluated prospectively. International collaboration, including a prospective audit of the results of implementing these consensus recommendations, is required to expand the evidence base for the design of optimum care pathways.

Human type 1 diabetes (T1D) is an autoimmune disease associated with major histocompatibility complex polymorphisms, β-cell autoantibodies, and autoreactive T cells. However, there is increasing evidence that innate cells may also play critical roles in T1D. We aimed to monitor peripheral immune cells in early stages of T1D (i.e., in healthy autoantibody-positive subjects) and in more advanced phases of the disease (i.e., at disease onset and years after diagnosis). We found a mild but significant and reproducible peripheral neutropenia that both precedes and accompanies the onset of T1D. This reduction was not due to peripheral neutrophil cell death, impaired differentiation, or the presence of anti-neutrophil antibodies. Neutrophils were observed by electron microscopy and immunohistochemical analysis in the exocrine pancreas of multiorgan donors with T1D (both at onset and at later stages of the disease) and not in that of multiorgan donors with type 2 diabetes or nondiabetic donors. These pancreas-infiltrating neutrophils mainly localized at the level of very small blood vessels. Our findings suggest the existence of a hitherto unrecognized clinical phenotype that might reflect unexplored pathogenic pathways underlying T1D.

Intra‐arterial transplantation of mesoangioblasts proved safe and partially efficacious in preclinical models of muscular dystrophy. We now report the first‐in‐human, exploratory, non‐randomized open‐label phase I–IIa clinical trial of intra‐arterial HLA‐matched donor cell transplantation in 5 Duchenne patients. We administered escalating doses of donor‐derived mesoangioblasts in limb arteries under immunosuppressive therapy (tacrolimus). Four consecutive infusions were performed at 2‐month intervals, preceded and followed by clinical, laboratory, and muscular MRI analyses. Two months after the last infusion, a muscle biopsy was performed. Safety was the primary endpoint. The study was relatively safe: One patient developed a thalamic stroke with no clinical consequences and whose correlation with mesoangioblast infusion remained unclear. MRI documented the progression of the disease in 4/5 patients. Functional measures were transiently stabilized in 2/3 ambulant patients, but no functional improvements were observed. Low level of donor DNA was detected in muscle biopsies of 4/5 patients and donor‐derived dystrophin in 1. Intra‐arterial transplantation of donor mesoangioblasts in human proved to be feasible and relatively safe. Future implementation of the protocol, together with a younger age of patients, will be needed to approach efficacy. Synopsis This study reports a safe, first‐in‐human mesoangioblast cell therapy to treat Duchenne muscular dystrophy (DMD) in 5 young patients, using a successful preclinical strategy, as an exploratory non‐randomized open‐label phase I–IIa clinical trial of intra‐arterial HLA‐matched donor cell transplantation. Five patients affected by DMD were treated by intra‐arterial infusions of escalating doses of HLA‐matched donor mesoangioblasts. The trial was overall safe but showed minimal, if any, efficacy. Data analysis suggested to treat patients at an earlier stage of the disease, optimize in in vitro models each single step of the transplantation protocol, and use genetically corrected, autologous mesoangioblasts in a future trial.

In September 2018, an international meeting of doctors of various disciplines, with expertise in the detection and treatment of DDH, was held in Csolyospalos, Hungary. The aim was to achieve consensus on the detection and early treatment of the condition and to develop a standardized system of teaching and training for hip ultrasound. There was strong agreement that US screening is essential. Specifically the Graf technique was selected as the technique of choice. Universal US screening was strongly favored. Screening should be carried out as soon as possible, but not later than the sixth week of age. US screening is cost-effective, does not result in overtreatment, and contributes to a reduction of long-term consequences. The essential principle of treatment is timely application of a device to achieve reduction, retention and maturation, by holding the hips in flexion, and a safe degree of abduction. It was agreed that the effectiveness of any screening policy depends on the correct scanning technique. Therefore, standardization of teaching and training of the Graf technique is mandatory. A unified teaching policy and materials should be developed for this purpose. Certification, re-certification and audit were discussed. The group, which has been formalized as the International Interdisciplinary Consensus Committee On DDH Evaluation (ICODE), will continue to meet and work towards establishing international consensus on DDH, standardizing and developing teaching and training of the Graf technique for hip US, and maintaining standards for detection and management.

Purpose: The aim of this study was to describe a subtalar extra-articular screw arthroereisis (SESA) technique for the correction of flexible flatfoot (FFF) in children and report the outcome. Methods: From 1990 to 2012, data were collected on 485 patients who underwent SESA at the San Raffaele Hospital. The average age of the patient cohort was 11.5 ± 1.81 years (range 5.0–17.9 years; median 11.5 years). Inclusion criteria were FFF and marked flexible hindfoot valgus, and the exclusion criterion was rigid flatfoot. SESA was performed in 732 cases of FFF—bilaterally in 247 patients and monolaterally in 238 patients. Results: The values of the pre- and post-SESA weight-bearing X-ray angles were 146° ± 7° and 129° ± 5°, respectively, for the Costa-Bartani angle, 43° ± 8° and 25° ± 6°, respectively, for the talar inclination angle and 11° ± 6° and 14° ± 5°, respectively, for calcaneal pitch ( p 20 years of experience, we believe that SESA is an optimal technique for the correction of FFF as it is simple and can be performed rapidly, and the corrective effect results from the screw's mechanical and proprioceptive effect. The indication for surgery must be accurate. We suggest that the patient be at least 10 years of age in order that all of the foot's growth potential can be utilized and to allow for spontaneous resolution and thereby avoid the possibility of over-treatment.