Severe obesity and diabetes insipidus in a patient with PCSK1 deficiency.

Non-synonymous mutations affecting both alleles of PCSK1 (proprotein convertase 1/3) are associated with obesity and impaired prohormone processing. We report a proband who was compound heterozygous for a maternally inherited frameshift mutation and a paternally inherited 474kb deletion that encompasses PCSK1, representing a novel genetic mechanism underlying this phenotype. Although pro-vasopressin is not a known physiological substrate of PCSK1, the development of central diabetes insipidus in this proband suggests that PCSK1 deficiency can be associated with impaired osmoregulation.ISF and SOR were supported by the Wellcome Trust, the MRC Centre for Obesity and Related Disorders and the UK NIHR Cambridge Biomedical Research Centre.This is the final published version. It first appeared at http://www.sciencedirect.com/science/article/pii/S1096719213001145#

Vitamin D status in pediatric irritable bowel syndrome.

IMPORTANCE:Irritable bowel syndrome (IBS) is associated with significant morbidity in children and adolescents, and the therapeutic efficacy of available treatment options is limited. The role of vitamin D supplementation in pediatric IBS is unclear as the vitamin D status of pediatric patients with IBS is unknown. Equally, the relationship of vitamin D status with psychosomatic symptoms in children and adolescents is unclear. AIM:To characterize the vitamin D status of pediatric patients with IBS using a case-control study design. HYPOTHESIS:Serum 25-hydroxyvitamin D [25(OH)D] concentration will be similar between patients with IBS and controls. SUBJECTS AND METHODS:A retrospective case-controlled study of 116 controls (age 14.6 ± 4.3 y), female (n = 67; 58%) and 55 subjects with IBS (age 16.5 ± 3.1y), female (n = 44; 80%). Overweight was defined as BMI of ≥85th but 90% of IBS subjects had vitamin D deficiency at a cut-off point of 50% of the subjects with IBS had vitamin D deficiency. This is a much higher prevalence of vitamin D deficiency compared to IBD and other malabsorption syndromes. Monitoring for vitamin D deficiency should be part of the routine care for patients with IBS. Randomized control trials are warranted to determine the role of adjunctive vitamin D therapy in pediatric IBS

Correction: Vitamin D status in pediatric irritable bowel syndrome.

[This corrects the article DOI: 10.1371/journal.pone.0172183.]

Splenic pseudoaneurysm in a child with hereditary pancreatitis

Splenic artery pseudoaneurysm (SAP) formation is an uncommon complication of pancreatitis. It is believed to be the result of vascular erosion by pancreatic enzymes, a process that compromises the integrity of the splenic artery wall. The final result is a weak, expanded vessel wall that may hemorrhage into the peritoneal cavity or retroperitoneal space. There are no known reports of SAP in the pediatric population or in patients with hereditary pancreatitis. We report a case of SAP formation in a 5-year-old child with hereditary pancreatitis that was successfully managed via transcatheter coil embolization of the splenic artery

An Unusual Manifestation of Celiac Disease in an Adolescent With Down Syndrome and Graves Disease

We describe an adolescent girl with Down syndrome and Graves disease presenting with polymenorrhea as the initial symptom of Celiac disease

Box plot of the comparison of 25-hydroxyvitamin D values of patients with irritable bowel syndrome (IBS) and controls stratified by body mass index (BMI).

<p>This figure shows that serum 25(OH)D concentration was significantly higher in the normal-weight controls compared to the overweight/obese controls (69.8 ± 27.5 nmol/L vs. 58.3 ± 27.6, p = 0.03), and to both the normal-weight and overweight/obese IBS subjects. Serum 25(OH)D concentration was similar between the normal-weight IBS- and overweight/obese IBS subjects (p = 0.91) Note: 50 nmol/L = 20 ng/mL. Circles represent standard deviations.</p

A comparison of the characteristics of subjects with irritable bowel syndrome and controls.

<p>A comparison of the characteristics of subjects with irritable bowel syndrome and controls.</p

Boxplot of the comparison of 25(OH)D concentrations between the controls and IBS subjects with psychosomatic manifestations.

<p>This figure shows a significant difference in serum 25(OH)D between the 4 groups: IBS subjects with anxiety (n = 17), IBS subjects with depression (n = 14), and IBS subjects with migraines (n = 13), and the controls, (ANOVA, p = 0.004). <i>Post hoc</i> analysis revealed a significant difference in 25(OH)D between the controls and subjects with IBS and migraines (p = 0.01), but not for IBS patients with depression (p = 0.08), or IBS patients with anxiety (p = 0.44). Hatched boxes represent subjects with symptoms, while clear boxes represent subjects with no symptoms. Circles and asterisks represent standard deviations.</p

Evaluating cost per remission and cost of serious adverse events of advanced therapies for ulcerative colitis

Background: Determining the relative cost-effectiveness between advanced therapeutic options for ulcerative colitis (UC) may optimize resource utilization. We evaluated total cost per response, cost per remission, and cost of safety events for patients with moderately-to-severely active UC after 52 weeks of treatment with advanced therapies at standard dosing. Methods: An analytic model was developed to estimate costs from the US healthcare system perspective associated with achieving efficacy outcomes and managing safety outcomes for advanced therapies approved for the treatment of UC. Numbers needed to treat (NNT) for response and remission, and numbers needed to harm (NNH) for serious adverse events (SAEs) and serious infections (SIs) were derived from a network meta-analysis of pivotal trials. NNT for induction and maintenance were combined with drug regimen costs to calculate cost per clinical remission. Cost of managing AEs was calculated using NNH for safety outcomes and published costs of treating respective AEs. Results: Costs per remission were 205,240, 249,417, 267,463, 365,050, 579,622, 750,200, and 787,998 for tofacitinib 10 mg, tofacitinib 5 mg, infliximab, vedolizumab, golimumab, adalimumab, and ustekinumab, respectively. Incremental costs of SAEs and SIs collectively were 136,390, 90,333, 31,888, 31,061, 20,049, 12,059, and 0 for tofacitinib 5 mg, golimumab, adalimumab, tofacitinib 10 mg, infliximab, ustekinumab, and vedolizumab (reference), respectively. Conclusions: Tofacitinib was associated with the lowest cost per response and cost per remission, while vedolizumab had the lowest costs related to SAEs and SIs. Balancing efficacy versus safety is important when evaluating the costs associated with treatment of moderate-to-severe UC.</p