Brazilian consensus on gastroesophageal reflux disease: proposals for assessment, classification, and management

The Brazilian Consensus on Gastroesophageal Reflux Disease considers gastroesophageal reflux disease to be a chronic disorder related to the retrograde flow of gastroduodenal contents into the esophagus and/or adjacent organs, resulting in a variable spectrum of symptoms, with or without tissue damage. Considering the limitations of classifications currently in use, a new classification is proposed that combines three criteria-clinical, endoscopic, and pH-metric-providing a comprehensive and more complete characterization of the disease. The diagnosis begins with the presence of heartburn, acid regurgitation, and alarm manifestations (dysphagia, odynophagia, weight loss, GI bleeding, nausea and/or vomiting, and family history of cancer). Also, atypical esophageal, pulmonary, otorhinolaryngological, and oral symptoms may occur. Endoscopy is the first approach, particularly in patients over 40 yr of age and in those with alarm symptoms. Other exams are considered in particular cases, such as contrast radiological examination, scyntigraphy, manometry, and prolonged pH measurement. The clinical treatment encompasses behavioral modifications in lifestyle and pharmacological measures. Proton pump inhibitors in manufacturers' recommended doses are indicated, with doubling of the dose in more severe cases of esophagitis. The minimum time of administration is 6 wk. Patients who do not respond to medical treatment, including those with atypical manifestations, should be considered for surgical treatment. Of the complications of gastroesophageal reflux disease, Barrett's esophagus presents a potential development of adenocarcinoma; biopsies should be performed, independent of Barrett's esophagus extent or location. In this regard the designation "short Barrett's" is not important in terms of management and prognosis.     

Endoluminal delivery of radiofrequency energy to the gastroesophageal junction in uncomplicated GERD: efficacy and potential mechanism of action

OBJECTIVES: The endoluminal delivery of radiofrequency energy to the gastroesophageal junction has been shown to decrease symptoms of gastroesophageal reflux disease in a multicenter study. In this single-center trial, we sought to further examine its efficacy and physiological effects in patients with uncomplicated gastroesophageal reflux disease. METHODS: Patients with chronic heartburn requiring maintenance antisecretory therapy but without a hiatal hernia >2 cm, severe esophagitis, or complications of gastroesophageal reflux disease were prospectively studied. Radiofrequency energy was delivered to the gastroesophageal junction using a transorally delivered, flexible bougie-tipped catheter and a thermocouple-controlled generator, under sedation and analgesia. The primary outcome measure was effect on reflux symptoms, assessed at baseline and at 1, 3, and 6 months, after treatment. Other outcome measures included effects on antireflux medication use, quality of life, overall patient satisfaction, esophageal motility, esophageal acid exposure, esophageal wall thickness, appearance of the cardioesophageal flap valve, and vagal efferent function. RESULTS: A total of 18 patients underwent successful outpatient treatment without a serious adverse event. A significant improvement in symptom scores (Gastroesophageal Reflux Disease [GERD] Activity Index: 112.5 [range 76.2-140.6] vs 81.0 (74.2-97.6); p < 0.0001) and antacid use (17/wk [range 0-81] vs 0 (0-10); p < 0.0001) was noted at 6-month follow-up. No adverse effect on abdominal vagal function was identified and no significant change in any esophageal motility parameter was seen; however, a trend was noted toward a reduction in the number of transient lower esophageal sphincter relaxations induced by gastric air distension (3.5/h vs 1.0/h, p = 0.13). No detrimental effects on peristalsis or swallow-induced lower esophageal sphincter relaxation pressure were seen. Nonsignificant trends (p = 0.06) were noted regarding a decrease in the Hill score and an increase in esophageal wall thickness after treatment. Finally, although a decrease in all pH parameters in both the upper and lower esophagus was seen, none reached statistical significance. CONCLUSIONS: Radiofrequency energy delivery to the region of the gastroesophageal junction provides effective symptom relief over the short term in patients with uncomplicated gastroesophageal reflux disease. It may achieve its therapeutic effect by reducing the frequency of transient lower esophageal sphincter relaxations triggered by gastric distension.     

Recommendations for probiotic use--2008

Recommendations for the clinical use of probiotics were published after a Yale University Workshop in 2005. A similar workshop was held in 2007, and the recommendations were updated and extended into other areas. The recommendations are graded into an "A," "B," "C" or no category based on the expert's opinion and review by the workshop participants. An "A" recommendation is made for acute childhood diarrhea, prevention of antibiotic-associated diarrhea, preventing and maintaining remission in pouchitis, and in an immune response for the treatment and prevention of atopic eczema associated with cow's milk allergy. The group maintained several "B" recommendations in other areas of treating inflammatory bowel disease and irritable bowel syndrome. Although there are significant studies in the "B" group, most "B" recommendations did not reach an "A" level because of some negative studies or a limited number of studies. Many reports in the "C" recommendations were significant but fell short of receiving stronger ratings because of the size of reported patient studies, and also the factors that limited categories to the "B" rating.     

Combined NGS Approaches Identify Mutations in the Intraflagellar Transport Gene IFT140 in Skeletal Ciliopathies with Early Progressive Kidney Disease

Ciliopathies are genetically heterogeneous disorders characterized by variable expressivity and overlaps between different disease entities. This is exemplified by the short rib‐polydactyly syndromes, Jeune, Sensenbrenner, and Mainzer‐Saldino chondrodysplasia syndromes. These three syndromes are frequently caused by mutations in intraflagellar transport (IFT) genes affecting the primary cilia, which play a crucial role in skeletal and chondral development. Here, we identified mutations in IFT140, an IFT complex A gene, in five Jeune asphyxiating thoracic dystrophy (JATD) and two Mainzer‐Saldino syndrome (MSS) families, by screening a cohort of 66 JATD/MSS patients using whole exome sequencing and targeted resequencing of a customized ciliopathy gene panel. We also found an enrichment of rare IFT140 alleles in JATD compared with nonciliopathy diseases, implying putative modifier effects for certain alleles. IFT140 patients presented with mild chest narrowing, but all had end‐stage renal failure under 13 years of age and retinal dystrophy when examined for ocular dysfunction. This is consistent with the severe cystic phenotype of Ift140 conditional knockout mice, and the higher level of Ift140 expression in kidney and retina compared with the skeleton at E15.5 in the mouse. IFT140 is therefore a major cause of cono‐renal syndromes (JATD and MSS). The present study strengthens the rationale for IFT140 screening in skeletal ciliopathy spectrum patients that have kidney disease and/or retinal dystrophy.     

Molecular epidemiology of noroviruses associated with acute sporadic gastroenteritis in children: Global distribution of genogroups,genotypes and GII.4 variants

Noroviruses are a leading cause of epidemic and sporadic acute gastroenteritis worldwide. The development of sensitive molecular diagnostic techniques has revolutionized our understanding of norovirus epidemiology over the past two decades, but norovirus strain types associated with sporadic gastroenteritis remain poorly described. Therefore, we conducted a systematic review of studies performed after 2000 to clarify the genotypic distribution of noroviruses in children (≤18 years of age) with sporadic acute gastroenteritis. Genogroup GII norovirus was the most prevalent, accounting for 96% of all sporadic infections. GII.4 was the most prevalent genotype, accounting for 70% of the capsid genotypes and 60% of the polymerase genotypes, followed by the capsid genotype GII.3 (16%) and the polymerase genotype GII.b (14%). The most common ORF1/ORF2 inter-genotype recombinants were GII.b, GII.12, and GII.4 polymerase genotypes combined with the capsid genotype GII.3, accounting for 19% of all genotyped strains. The distribution of GII.4 variants over the last decade was dominated by successive circulation of GII.4/2002, GII.4/2004, GII.4/2006b, and GII.4/2008 with GII.4/2006b continuing to date. Genotypes GII.4 and GII.3 have predominated in children during the past decade; this is most notable in the global emergence of GII.4 variant noroviruses. As the burden of rotavirus disease decreases following the introduction of childhood immunization programs, the relative importance of norovirus in the etiology of acute childhood gastroenteritis will likely increase. In order for a successful norovirus vaccine to be developed, it should provide immunity against strains with capsid genotypes GII.4 and GII.3.     

Gastrointestinal motility problems in critical care: A clinical perspective

Advances in surgery, anesthesia and intensive care have led to a dramatic increase in the number of patients who spend time in our intensive care units (ICU). Gastrointestinal (GI) motility disorders are common complications in the intensive care setting and are predictors of increased mortality and length of the stay in the ICU. Several risk factors for developing GI motility problems in the ICU setting have been identified and include sepsis, being on mechanical ventilation and the use of vasopressors, opioids or anticholinergic medications. Our focus is on the most common clinical manifestations of GI motor dysfunction in the ICU patient: gastroesophageal reflux, gastroparesis, ileus and acute pseudo‐obstruction of the colon.     

The genetics of phaeochromocytoma: using clinical features to guide genetic testing

Phaeochromocytoma is a rare, usually benign, tumour predominantly managed by endocrinologists. Over the last decade, major advances have been made in understanding the molecular genetic basis of adrenal and extra-adrenal phaeochromocytoma (also referred to as adrenal phaeochromocytoma (aPCA) and extra-adrenal functional paraganglioma (eFPGL)). In contrast to the previously held belief that only 10% of cases had a genetic component, currently about one-third of all aPCA/eFPGL cases are thought to be attributable to germline mutations in at least nine genes (NF1, RET, SDHA, SDHB, SDHC, SDHD, TMEM127, MAX and VHL). Recognition of inherited cases of aPCA/eFPGL is critical for optimal patient management. Thus, the identification of a germline mutation can predict risks of malignancy, recurrent disease, associated non-chromaffin tumours and risks to other family members. Mutation carriers should be offered specific surveillance programmes (according to the relevant gene). In this review, we will describe the genetics of aPCA/eFPGL and strategies for genetic testing.