Pemphigus Vulgaris With Esophageal Involvement in an Atopic Child Successfully Treated With Dupilumab.

We report the case of a 3-year-old boy who was diagnosed with childhood pemphigus vulgaris having developed oral lesions, gastrointestinal symptoms with esophageal involvement, and failure to thrive. He had a markedly increased total serum IgE level and peripheral blood eosinophilia. The pemphigus was recalcitrant to conventional therapies and, based on the coexisting characteristics of Th2 immune deviation, he was treated with dupilumab and has had sustained clinical improvement since starting treatment.

Evidence-Informed Expert Recommendations for the Management of Celiac Disease in Children.

Although the need for effective long-term follow-up for patients with celiac disease (CD) has been recognized by many expert groups, published practice guidelines have not provided a clear approach for the optimal management of these patients. In an attempt to provide a thoughtful and practical approach for managing these patients, a group of experts in pediatric CD performed a critical review of the available literature in 6 categories associated with CD to develop a set of best practices by using evidence-based data and expert opinion. The 6 categories included the following: bone health, hematologic issues, endocrine problems, liver disease, nutritional issues, and testing.

Nonclinical aspects of venous thrombosis in pregnancy.

Pregnancy is a hypercoagulable state which carries an excess risk of maternal venous thrombosis. Endothelial injury, alterations in blood flow and activation of the coagulation pathway are proposed to contribute to the hypercoagulability. The risk for thrombosis may be accentuated by certain drugs and device implants that directly or indirectly affect the coagulation pathway.

Development and validation of a celiac disease quality of life instrument for North American children.

Objective: Given the social constraints imposed by a gluten-free diet, it can be hypothesized that children with celiac disease (CD) living in the United States have a reduced health-related quality of life (HRQOL); however, there is no validated CD-specific HRQOL instrument for children living in the United States. The goals of this study were to develop and validate a CD-specific HRQOL instrument for children 8 to 18 years of age with CD and to report HRQOL in these children using both generic- and disease-specific instruments.

Methods: This was a prospective study using focus group methodology to develop a CD-specific HRQOL instrument that was then administered to children 8 to 18 years of age with CD living throughout the United States.

Anticipated classes of new medications and molecular targets for pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) remains a life-limiting condition with a major impact on the ability to lead a normal life. Although existing therapies may improve the outlook in some patients there remains a major unmet need to develop more effective therapies in this condition. There have been significant advances in our understanding of the genetic, cell and molecular basis of PAH over the last few years.

Is randomization to placebo safe? Risk in placebo-controlled angina trials: angina risk meta-analysis.

Objective: It was the aim of this study to document the risks of symptomatic patients with angina in placebo-controlled, anti-anginal drug development trials in which symptom-limited exercise testing was used as the primary endpoint.

Patients And Methods: The original case report forms submitted to the United States Food and Drug Administration in support of approval of new or supplemental new drug applications between 1973 and 2001 were identified and subjected to a by-patient meta-analysis, utilizing both a maximum likelihood analysis and classical Mantel-Haenszel methods.

Results: There were 63 placebo-controlled, clinical trials that randomized 10,865 patients, with 1,047 patient-years of observation time.

Celiac disease in normal-weight and overweight children: clinical features and growth outcomes following a gluten-free diet.

Objectives: There are few data on pediatric celiac disease in the United States. The aim of our study was to describe the presentation of celiac disease among children with a normal and an elevated body mass index (BMI) for age, and to study their BMI changes following a gluten-free diet (GFD).

Patients And Methods: One hundred forty-two children (age 13 months-19 years) with biopsy-proven celiac disease, contained in a registry of patients studied at our center from 2000 to 2008, had follow-up growth data available.

Biomarkers of endothelial cell activation serve as potential surrogate markers for drug-induced vascular injury.

Drug-induced vascular injury (DIVI) is a nonclinical finding that often confounds the toxicological evaluation of investigational drugs, but there is an absence of qualified biomarkers that can be used to detect and monitor its appearance in animals and patients during drug development and clinical use. It is well known that endothelial cell (EC) activation plays a key role in the expression and evolution of DIVI, and the various immunological and inflammatory factors involved in its expression may serve as potential biomarker candidates. Activated ECs change their morphology and gene expression, generating endothelial adhesion molecules, pro-coagulant molecules, cytokines, chemokines, vasodilators, nitric oxide, and acute-phase reactants.

Renal biomarker qualification submission: a dialog between the FDA-EMEA and Predictive Safety Testing Consortium.

The first formal qualification of safety biomarkers for regulatory decision making marks a milestone in the application of biomarkers to drug development. Following submission of drug toxicity studies and analyses of biomarker performance to the Food and Drug Administration (FDA) and European Medicines Agency (EMEA) by the Predictive Safety Testing Consortium's (PSTC) Nephrotoxicity Working Group, seven renal safety biomarkers have been qualified for limited use in nonclinical and clinical drug development to help guide safety assessments. This was a pilot process, and the experience gained will both facilitate better understanding of how the qualification process will probably evolve and clarify the minimal requirements necessary to evaluate the performance of biomarkers of organ injury within specific contexts.

The risks associated with short-term placebo-controlled antihypertensive clinical trials: a descriptive meta-analysis.

Short-term (4-8 weeks) placebo-controlled trials are used to evaluate new antihypertensive drug treatment. To evaluate the consequences of such practice, a descriptive meta-analysis was conducted, consisting of blinded review of original case report forms for all patients who died or left a study before its completion for all short-term, placebo-controlled hypertension trials submitted to the Food and Drug Administration from 1973 through 2001. There were 93 marketing applications or supplements involving 590 individual trials that involved 86137 randomized patients (64438 randomized to experimental drug and 21 699 randomized to placebo) with 12658 patient years of observation.

Endothelial injury in the initiation and progression of vascular disorders.

Endothelial cell dysfunction is considered to be an early event which subsequently leads to vascular wall disorders. Ultrastructural studies indicate that the endothelial cell changes involve membrane damage, increased permeability, swelling and necrosis. The endothelial cell loss of function could be as a result of changes in hemodynamic forces (shear and/or hoop stress), direct drug-induced cytotoxicity, mechanical device implant-induced injury and/or immune-mediated mechanisms.

Presentation of pediatric celiac disease in the United States: prominent effect of breastfeeding.

Childhood celiac disease (CD) is considered rare in the United States. Consequently there are few data concerning its clinical presentation. A validated questionnaire was distributed to families of children with CD.

Acute hepatic failure in a child treated with lamotrigine.

An 8-year-old boy with a known seizure disorder that was being treated with lamotrigine developed acute hepatic failure. The patient, who had been well previously, presented with jaundice, elevated liver enzymes, and a coagulopathy. After discontinuation of lamotrigine and aggressive resuscitation, the patient made an uneventful recovery.

Use of neomycin as the prophylaxis against recurrent cholangitis after Kasai portoenterostomy.

Ascending cholangitis after portoenterostomy for biliary atresia often leads to significant morbidity. The long-term prognosis also involves recurrent and frequently recalcitrant bouts of cholangitis. Attempts at prophylaxis with use of oral antibiotics are frequently unsuccessful.

Regulatory considerations for oligonucleotide drugs: updated recommendations for pharmacology and toxicology studies.

This article describes pharmacology and toxicity studies for oligonucleotide drugs that are recommended for inclusion in the initial Investigational New Drug Application (IND), a first request to use an investigational drug in clinical trials. Recent observations of non-sequence-dependent cardiovascular toxicity and deaths in monkeys following intravenous infusions of phosphorothioates have raised a potential safety concern for oligonucleotide drugs. This concern should be considered by drug sponsors in designing pre-IND nonclinical development programs and Phase I clinical protocols.

Low methionine ingestion by rats extends life span.

Dietary energy restriction has been a widely used means of experimentally extending mammalian life span. We report here that lifelong reduction in the concentration of a single dietary component, the essential amino acid L-methionine, from 0.86 to 0.

Association of congenital hepatic fibrosis with autosomal dominant polycystic kidney disease. Report of a family with review of literature.

The association of autosomal recessive polycystic kidney disease (ARPKD) with congential hepatic fibrosis (CHF) is well known; a rare occurrence is that of congenital hepatic fibrosis with autosomal dominant polycystic kidney disease (ADPKD). We report a family with ADPKD in which congenital hepatic fibrosis with severe portal hypertension (PHT) presented in a 4-year-old girl; the kidneys were initially normal. Typical changes of autosomal dominant polycystic kidney disease developed in the next decade and were also found in the mother and sister (neither of whom had any evidence of portal hypertension).

Obstruction of the Roux limb after portoenterostomy for biliary atresia: a delayed complication.

We report the case of a 5-year-old girl who underwent a Kasai portoenterostomy for extrahepatic biliary atresia. The conduit was exteriorized until 11 months of age. She was doing well, with stable portal hypertension until she suddenly developed jaundice, acholic stools, and bacteremia not responsive to a course of steroids and intravenous antibiotics.