Clinical and economic profile of prucalopride in the treatment of chronic constipation in women

Chronic constipation is a common disorder, especially in women. Options available for different subgroups of constipation are limited and in most cases unsatisfactory. The most severe forms of chronic constipation often require the use of laxatives in high doses or the use of invasive therapies. The introduction of a new drug, such as prucalopride, active in promoting intestinal transit, can help to improve the therapy of patients with chronic idiopathic constipation who have not found relief from previous treatment with laxatives. In this review, after a brief discussion of pathophysiology and pharmacotherapy of chronic constipation, we evaluate the pharmacological profile, therapeutic and cost of prucalopride, recently authorized in the EU countries and also available in Italy for the treatment of chronic constipation in women who did not benefit from the use of laxative

Pyridostigmine in pediatric Intestinal pseudo-obstruction. case report of a 2-year old girl and literature review

Pediatric chronic intestinal pseudo-obstruction is a rare disorder characterized by a severe impairment of gastrointestinal motility leading to intestinal obstruction symptoms in the absence of mechanical causes. The diagnosis is usually clinical and diagnostic work is usually aimed to rule out mechanical obstruction and to identify any underlying diseases. Treatment is challenging and requires a multidisciplinary effort. In this manuscript we describe the youngest child successfully treated with the orally administrable, longacting, reversible anti-cholinesterase drug, pyridostigmine. Like other drugs belonging to cholinesterase inhibitors, pyridostigmine enhances gut motility by increasing acetylcholine availability in the enteric nervous system and neuro-muscular junctions. Based on the direct evidence from the reported case, we reviewed the current literature on the use of pyridostigmine in severe pediatric dysmotility focusing on intestinal pseudo-obstruction. The overall data emerged from the few published studies suggest that pyridostigmine is an effective and usually well tolerated therapeutic options for patients with intestinal pseudo-obstruction. More specifically, the main results obtained by pyridostigmine included marked reduction of abdominal distension, reduced need of parenteral nutrition, and improvement of oral feeding. The present case and review on pyridostigmine pave the way for eagerly awaited future randomized controlled studies testing the efficacy of cholinesterase inhibitors in pediatric severe gut dysmotility

Prenatal diagnosis and follow-up of a case of branchio-oto-renal syndrome displays renal growth impairment after the second trimester

Branchio-oto-renal syndrome combines branchial arch defects, hearing impairment and renal malformations or hypoplasia. Due to the high phenotypic variability, prenatal diagnosis has a limited prognostic value in mutation-positive cases. We report the first branchio-oto-renal syndrome molecular prenatal diagnosis and ultrasonographic follow-up, showing a normal renal growth until the 24th week of pregnancy, a growth deceleration during the third trimester and a renal volume recovery during the first months of life

Pathophysiology and Clinical Management of Bile Acid Diarrhea

Bile acid malabsorption (BAM) represents a common cause of chronic diarrhea whose prevalence is under-investigated. We reviewed the evidence available regarding the pathophysiology and clinical management of bile acid diarrhea (BAD). BAD results from dysregulation of the enterohepatic recirculation of bile acids. It has been estimated that 25-33% of patients with functional diarrhea and irritable bowel syndrome with diarrhea have BAM. Currently, the selenium homotaurocholic acid test is the gold standard for BAD diagnosis and severity assessment. However, it is an expensive method and not widely available. The validation of the utility in the clinical practice of several other serum markers, such as 7 alpha-hydroxy-4-cholesten-3-one (C4) and the fibroblast growth factor 19 (FGF19) is ongoing. The first-line treatment of patients with BAD is bile acid sequestrants. Patients that are refractory to first-line therapy should undergo further diagnostics to confirm the diagnosis and to treat the underlying cause of BAD. An early and correct diagnosis of BAD would improve patient's quality of life, avoiding additional diagnostic tests that burden health care systems. Considering the limited availability and tolerability of specific medications for BAD treatment, future research is awaited to identify other therapeutic approaches, such as gut microbiota modulating therapies

Chronic constipation in the elderly: a primer for the gastroenterologist

Constipation is a frequently reported bowel symptom in the elderly with considerable impact on quality of life and health expenses. Disease-related morbidity and even mortality have been reported in the affected frail elderly. Although constipation is not a physiologic consequence of normal aging, decreased mobility, medications, underlying diseases, and rectal sensory-motor dysfunction may all contribute to its increased prevalence in older adults. In the elderly there is usually more than one etiologic mechanism, requiring a multifactorial treatment approach. The majority of patients would respond to diet and lifestyle modifications reinforced by bowel training measures. In those not responding to conservative treatment, the approach needs to be tailored addressing all comorbid conditions. In the adult population, the management of constipation continues to evolve as well as the understanding of its complex etiology. However, the constipated elderly have been left behind while gastroenterology consultations for this common conditions are at a rise for the worldwide age increment. Aim of this review is to provide an update on epidemiology, quality of life burden, etiology, diagnosis, current approaches and limitations in the management of constipation in the older ones to ease the gastroenterologists’ clinic workload

Autoimmune Hepatitis and Celiac Disease: Case Report Showing an Entero-Hepatic Link

Celiac disease is an autoimmune disorder primarily targeting the small bowel, although extraintestinal extensions have been reported. The autoimmune processes can affect the liver with manifestations such as primary biliary cirrhosis and autoimmune hepatitis. We describe a 61-year-old woman with celiac disease and an increased levels of aminotransferases. The persistence of increased levels of aminotransferases after 1 year of gluten-free diet and the positivity for an anti-nuclear and anti-double-strand DNA antibodies led to a misdiagnosis of systemic lupus erythematosus-related hepatitis. Based on these findings the patient was placed on steroids, which after a few months were stopped because of the onset of diabetes mellitus. Soon after steroid withdrawal, the patient had a marked increase in aminotransferases and γ-globulins, and a liver biopsy revealed chronic active hepatitis. A course of three months of steroids and azathioprine normalized both biochemical and clinical parameters. Currently the patient is symptom-free and doing well. In conclusion, a hypertransaminasemia persisting after a gluten-free diet should be interpreted as a sign of coexisting autoimmune liver disease. Any autoantibody positivity (in this case to ANA and anti-dsDNA) should be carefully considered in order to avoid misdiagnosis delaying appropriate clinical management

Clinical Impact of Pretransplant Multidrug-Resistant Gram-Negative Colonization in Autologous and Allogeneic Hematopoietic Stem Cell Transplantation

Abstract Multidrug-resistant Gram-negative bacteria (MDR-GNB) are an emerging cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Three-hundred forty-eight consecutive patients transplanted at our hospital from July 2012 to January 2016 were screened for a pretransplant MDR-GNB colonization and evaluated for clinical outcomes. A pretransplant MDR-GNB colonization was found in 16.9% of allo-HSCT and in 9.6% of auto-HSCT recipients. Both in auto- and in allo-HSCT, carriers of a MDR-GNB showed no significant differences in overall survival (OS), transplant-related mortality (TRM), or infection-related mortality (IRM) compared with noncarriers. OS at 2 years for carriers compared with noncarriers was 85% versus 81% ( P  = .262) in auto-HSCT and 50% versus 43% ( P  = .091) in allo-HSCT. TRM at 2 years was 14% versus 5% ( P  = .405) in auto-HSCT and 31% versus 25% ( P  = .301) in allo-HSCT. IRM at 2 years was 14% versus 2% ( P  = .142) in auto-HSCT and 23% versus 14% ( P  = .304) in allo-HSCT. In multivariate analysis, only grade III to IV acute graft-versus-host disease was an independent factor for reduced OS ( P P P P  = .207). We conclude that in this extended single-center experience, a pretransplant MDR-GNB colonization did not significantly influence OS, TRM, and IRM both in auto- and allo-HSCT settings and that MDR-GNB attributed mortality can be controlled in carriers when an early pre-emptive antimicrobial therapy is started in case of neutropenic fever

Expression and regulation of α-transducin in the pig gastrointestinal tract

Taste signalling molecules are found in the gastrointestinal (GI) tract suggesting that they participate to chemosensing. We tested whether fasting and refeeding affect the expression of the taste signalling molecule, a-transducin (Gatran), throughout the pig GI tract and the peptide content of Gatran cells. The highest density of Gatran-immunoreactive (IR) cells was in the pylorus, followed by the cardiac mucosa, duodenum, rectum, descending colon, jejunum, caecum, ascending colon and ileum. Most Gatran-IR cells contained chromogranin A. In the stomach, many Gatran-IR cells contained ghrelin, whereas in the upper small intestine many were gastrin/cholecystokinin-IR and a few somatostatin-IR. Gatran-IR and Gagust-IR colocalized in some cells. Fasting (24 h) resulted in a significant decrease in Gatran-IR cells in the cardiac mucosa (29.3 0.8 versus 64.8 1.3, P < 0.05), pylorus (98.8 1.7 versus 190.8 1.9, P < 0.0 l), caecum (8 0.01 versus 15.5 0.5, P < 0.01), descending colon (17.8 0.3 versus 23 0.6, P < 0.05) and rectum (15.3 0.3 versus 27.5 0.7, P < 0.05). Refeeding restored the control level of Gatran-IR cells in the cardiac mucosa. In contrast, in the duodenum and jejunum, Gatran-IR cells were significantly reduced after refeeding, whereas Gatran-IR cells density in the ileum was not changed by fasting/refeeding. These findings provide further support to the concept that taste receptors contribute to luminal chemosensing in the GI tract and suggest they are involved in modulation of food intake and GI function induced by feeding and fasting

a new clinicobiological scoring system for the prediction of infection related mortality and survival after allogeneic hematopoietic stem cell transplantation

Abstract Infection-related mortality (IRM) is a substantial component of nonrelapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). No scores have been developed to predict IRM before transplantation. Pretransplantation clinical and biochemical data were collected from a study cohort of 607 adult patients undergoing allo-HSCT between January 2009 and February 2017. In a training set of 273 patients, multivariate analysis revealed that age >60 years ( P  = .003), cytomegalovirus host/donor serostatus different from negative/negative ( P P  = .004), and pretransplantation IgM level P  = .028) were independent predictors of increased IRM. Based on these results, we developed and subsequently validated a 3-tiered weighted prognostic index for IRM in a retrospective set of patients (n = 219) and a prospective set of patients (n = 115). Patients were assigned to 3 different IRM risk classes based on this index score. The score significantly predicted IRM in the training set, retrospective validation set, and prospective validation set ( P P P

Anatomical Laser Microdissection of the Ileum Reveals mtDNA Depletion Recovery in A Mitochondrial Neuro-Gastrointestinal Encephalomyopathy (MNGIE) Patient Receiving Liver Transplant

mitochondrial neuro-gastrointestinal encephalomyopathy (MNGIE) is a rare genetic disorder characterized by thymidine phosphorylase (TP) enzyme defect. The absence of TP activity induces the imbalance of mitochondrial nucleotide pool, leading to impaired mitochondrial DNA (mtDNA) replication and depletion. Since mtDNA is required to ensure oxidative phosphorylation, metabolically active tissues may not achieve sufficient energy production. The only effective life-saving approach in MNGIE has been the permanent replacement of TP via allogeneic hematopoietic stem cell or liver transplantation. However, the follow-up of transplanted patients showed that gut tissue changes do not revert and fatal complications, such as massive gastrointestinal bleeding, can occur. The purpose of this study was to clarify whether the reintroduction of TP after transplant can recover mtDNA copy number in a normal range. Using laser capture microdissection and droplet-digital-PCR, we assessed the mtDNA copy number in each layer of full-thickness ileal samples of a naive MNGIE cohort vs. controls and in a patient pre- and post-TP replacement. The treatment led to a significant recovery of gut tissue mtDNA amount, thus showing its efficacy. Our results indicate that a timely TP replacement is needed to maximize therapeutic success before irreversible degenerative tissue changes occur in MNGIE