Effective combination treatment of GD2-expressing neuroblastoma and Ewing's sarcoma using anti-GD2 ch14.18/CHO antibody with Vγ9Vδ2+ γδT cells.

Gamma delta T lymphocytes (γδT cells) have pleiotropic properties including innate cytotoxicity, which make them attractive effectors for cancer immunotherapy. Combination treatment with zoledronic acid and IL-2 can activate and expand the most common subset of blood γδT, which express the Vγ9Vδ2 T cell receptor (TCR) (Vδ2 T cells). Vγ9Vδ2 T cells are equipped for antibody-dependent cell-mediated cytotoxicity (ADCC) through expression of the low-affinity FcγR CD16.

EPG5-related Vici syndrome: a paradigm of neurodevelopmental disorders with defective autophagy.

Vici syndrome is a progressive neurodevelopmental multisystem disorder due to recessive mutations in the key autophagy gene EPG5. We report genetic, clinical, neuroradiological, and neuropathological features of 50 children from 30 families, as well as the neuronal phenotype of EPG5 knock-down in Drosophila melanogaster. We identified 39 different EPG5 mutations, most of them truncating and predicted to result in reduced EPG5 protein.

Quantitative Histomorphometry of the Healthy Peritoneum.

The peritoneum plays an essential role in preventing abdominal frictions and adhesions and can be utilized as a dialysis membrane. Its physiological ultrastructure, however, has not yet been studied systematically. 106 standardized peritoneal and 69 omental specimens were obtained from 107 patients (0.

Gaseous nitric oxide to treat antibiotic resistant bacterial and fungal lung infections in patients with cystic fibrosis: a phase I clinical study.

Background: Individuals with cystic fibrosis (CF) receive antibiotics continuously throughout their entire life which leads to drug resistant microbial lung infections which are difficult to treat. Nitric oxide (NO) gas possesses antimicrobial activity against a wide variety of microorganisms in vitro, in vivo in animal models and a phase I study in healthy adults showed administration of intermittent 160 ppm NO to be safe.

Methods: We assessed feasibility and safety of inhaled NO in eight CF patients who received 160 ppm NO for 30 min, three times daily for 2 periods of 5 days.

The second European interdisciplinary Ewing sarcoma research summit--A joint effort to deconstructing the multiple layers of a complex disease.

Despite multimodal treatment, long term outcome for patients with Ewing sarcoma is still poor. The second "European interdisciplinary Ewing sarcoma research summit" assembled a large group of scientific experts in the field to discuss their latest unpublished findings on the way to the identification of novel therapeutic targets and strategies. Ewing sarcoma is characterized by a quiet genome with presence of an EWSR1-ETS gene rearrangement as the only and defining genetic aberration.

Effects of the New Generation Synthetic Reconstituted Surfactant CHF5633 on Pro- and Anti-Inflammatory Cytokine Expression in Native and LPS-Stimulated Adult CD14+ Monocytes.

Background: Surfactant replacement therapy is the standard of care for the prevention and treatment of neonatal respiratory distress syndrome. New generation synthetic surfactants represent a promising alternative to animal-derived surfactants. CHF5633, a new generation reconstituted synthetic surfactant containing SP-B and SP-C analogs and two synthetic phospholipids has demonstrated biophysical effectiveness in vitro and in vivo.

The extended phenotype of LPS-responsive beige-like anchor protein (LRBA) deficiency.

Background: LPS-responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency caused by biallelic mutations in LRBA that abolish LRBA protein expression.

Objective: We sought to report the extended phenotype of LRBA deficiency in a cohort of 22 LRBA-deficient patients.

Methods: Clinical criteria, protein detection, and genetic sequencing were applied to diagnose LRBA deficiency.

Effect of TH2 cytokines and interferon gamma on beat frequency of human respiratory cilia.

Background: In asthmatic airways secondary ciliary dyskinesia contributes to impaired mucociliary clearance. To investigate underlying mechanisms, we studied the effects of cytokines associated with asthma phenotype on the ciliary beat frequency (CBF) in a cell culture model of ciliated human respiratory epithelial cells.

Methods: Nasal respiratory epithelial cells of 21 patients were used to prepare multicellular cells (spheroids) in the presence of the T helper (TH) 2 cytokines interleukin (IL)-4, IL-5, IL-9 and IL-13, and the TH1 cytokine interferon gamma (IFN-γ).

Febrile urinary tract infection after pediatric kidney transplantation: a multicenter, prospective observational study.

Background: Febrile urinary tract infections (fUTIs) are common after kidney transplantation (KTx); however, prospective data in a multicenter pediatric cohort are lacking. We designed a prospective registry to record data on fUTI before and after pediatric KTx.

Methods: Ninety-eight children (58 boys and 40 girls) ≤ 18 years from 14 mid-European centers received a kidney transplant and completed a 2-year follow-up.

Assessment of intracardiac flow and vorticity in the right heart of patients after repair of tetralogy of Fallot by flow-sensitive 4D MRI.

Objectives: To comprehensively and quantitatively analyse flow and vorticity in the right heart of patients after repair of tetralogy of Fallot (rTOF) compared with healthy volunteers.

Methods: Time-resolved flow-sensitive 4D MRI was acquired in 24 rTOF patients and 12 volunteers. Qualitative flow evaluation was based on consensus reading of two observers.

Rapid Response to Cyclosporin A and Favorable Renal Outcome in Nongenetic Versus Genetic Steroid-Resistant Nephrotic Syndrome.

Background And Objectives: Treatment of congenital nephrotic syndrome (CNS) and steroid-resistant nephrotic syndrome (SRNS) is demanding, and renal prognosis is poor. Numerous causative gene mutations have been identified in SRNS that affect the renal podocyte. In the era of high-throughput sequencing techniques, patients with nongenetic SRNS frequently escape the scientific interest.

Transitional Care and Adherence of Adolescents and Young Adults After Kidney Transplantation in Germany and Austria: A Binational Observatory Census Within the TRANSNephro Trial.

Transition from child to adult-oriented care is widely regarded a challenging period for young people with kidney transplants and is associated with a high risk of graft failure. We analyzed the existing transition structures in Germany and Austria using a questionnaire and retrospective data of 119 patients transferred in 2011 to 2012. Most centers (73%) confirmed agreements on the transition procedure.

Exome sequencing of osteosarcoma reveals mutation signatures reminiscent of BRCA deficiency.

Osteosarcomas are aggressive bone tumours with a high degree of genetic heterogeneity, which has historically complicated driver gene discovery. Here we sequence exomes of 31 tumours and decipher their evolutionary landscape by inferring clonality of the individual mutation events. Exome findings are interpreted in the context of mutation and SNP array data from a replication set of 92 tumours.

Enthesopathy of the pectoralis major tendon mimicking osteoid osteoma. A case report with an unfortunate series of events.

Background: we present the case of an enthesopathy at the proximal humerus which was initially - due to the clinical history and a positive bone scintigraphy - regarded suspicious for metastatic breast cancer in a 50-year-old woman.

Case Report: after complementing radiographs and a magnetic resonance (MR) examination exhibiting a focally contrast enhancing juxtacortical osteolysis of the humerus, a metastasis seemed radiologically unlikely, but besides a traction-related periosteal reaction of the pectoralis major tendon an unusual osteoid osteoma could not unequivocally be ruled out. Although radiological follow-up was recommended the patient insisted on a surgical resection that was performed subsequently and confirmed an enthesopathy.

Scarlet fever: A not so typical exanthematous pharyngotonsillitis (based on 171 cases).

Aim: To describe the age, signs and clinical symptoms of children with scarlet fever at the present time, and to check whether they are equivalent to those with traditional streptococcal pharyngotonsillitis.

Study Design: An observational, retrospective study was conducted on the clinical records of 5500 children aged from 0 to 15 years attending a primary health care center. A record was made of the percentage of the cases in which signs and symptoms appear and the Centor score was calculated.

Multiple Major and Minor Anomalies Associated With Klippel-Feil Syndrome: A Case Report.

Klippel-Feil syndrome is defined as congenital fusion of two or more cervical vertebrae. In this article, we report a 55-year-old male patient with one-year history of neck pain, headaches, and one episode of syncope after a severe trauma. X-rays and magnetic resonance imaging of cervical spine revealed fused vertebral bodies of C2-C5.

Radiotherapy and subsequent thyroid cancer in German childhood cancer survivors: a nested case-control study.

Background: Radiotherapy is associated with a risk of subsequent neoplasms (SN) in childhood cancer survivors. It has been shown that children's thyroid glands are especially susceptible. The aim is to quantify the risk of a second neck neoplasm after primary cancer radiotherapy with emphasis on thyroid cancer.

X-linked hypophosphatemic rickets and sagittal craniosynostosis: three patients requiring operative cranial expansion: case series and literature review.

Purpose: A defect in a phosphate-regulating gene leads to the most common form of rickets: X-linked hypophosphatemic rickets (XLH) or vitamin D-resistant rickets (VDDR). XLH has been associated with craniosynostosis, the sagittal suture being the most commonly involved.

Methods: We present three patients with rickets and symptomatic sagittal suture craniosynostosis all of whom presented late (>2 years of age).

Frequency of Oral Mucositis and Local Virus Reactivation in Herpes Simplex Virus Seropositive Children with Myelosuppressive Therapy.

Background: Oral mucositis (OM) is a common chemo- and radiotherapy adverse effect in oncological pediatric patients. Herpes simplex virus (HSV) infection can cause a severe clinical course. We hypothesize, that HSV seropositivity is a risk factor for local HSV-1 reactivation and increased frequency of OM in patients with myelosuppressive therapies.

Cost-effectiveness of peer role play and standardized patients in undergraduate communication training.

Background: The few studies directly comparing the methodological approach of peer role play (RP) and standardized patients (SP) for the delivery of communication skills all suggest that both methods are effective. In this study we calculated the costs of both methods (given comparable outcomes) and are the first to generate a differential cost-effectiveness analysis of both methods.

Methods: Medical students in their prefinal year were randomly assigned to one of two groups receiving communication training in Pediatrics either with RP (N = 34) or 19 individually trained SP (N = 35).

Rat renal transplant model for mixed acute humoral and cellular rejection: Weak correlation of serum cytokines/chemokines with intragraft changes.

Background: Acute renal allograft rejection remains a major cause of allograft dysfunction; especially for episodes with mixed humoral and cellular character which can be detrimental for graft survival. We established a rat RT model with exclusive and complete MHC-disparity to investigate pathomechanisms of acute rejection and evaluate serum multiplex assays as a diagnostic tool in this context.

Methods: LEW rats receive congeneic LEW.

Synovial sarcoma is a gateway to the role of chromatin remodeling in cancer.

Patients afflicted with synovial sarcoma share the fate of other translocation positive sarcomas; the driver mutation for this cancer is known, yet no means to target the fusion protein SS18-SSX directly exist. Current chemotherapeutic regimens are minimally beneficial, particularly in patients with metastatic disease. SS18-SSX putatively promotes its oncogenic activity through protein-protein interactions that alter genetic programs through chromatin remodeling.

Nijmegen Breakage Syndrome: Clinical and Immunological Features, Long-Term Outcome and Treatment Options - a Retrospective Analysis.

Purpose: Nijmegen Breakage Syndrome (NBS) is a rare inherited condition, characterized by microcephaly, chromosomal instability, immunodeficiency, and predisposition to malignancy. This retrospective study, characterizing the clinical and immunological status of patients with NBS at time of diagnosis, was designed to assess whether any parameters were useful in disease prognosis, and could help determine patients qualified for hematopoietic stem cell transplantation.

Methods: The clinical and immunological characteristics of 149 NBS patients registered in the online database of the European Society for Immune Deficiencies were analyzed.

Insulin-like growth factor-1 receptor (IGF-1R) inhibition promotes expansion of human NK cells which maintain their potent antitumor activity against Ewing sarcoma cells.

Background: Patients with primary metastatic or relapsed Ewing sarcomas (EwS) have a poor prognosis. While inhibitory insulin-like growth factor 1 receptor (IGF-1R)-specific antibodies have shown single agent activity in some patients with refractory disease, effective therapeutic targeting will rely on optimal combinations with conventional or innovative therapies. Specifically, combination of inhibitory IGF-1R antibodies with adoptive transfer of activated natural killer (NK) cells may have therapeutic benefit in EwS without adding toxicity.