Maria de Fátima Correia Pimenta Servidoni

Measurements of CFTR-Mediated Cl- Secretion in Human Rectal Biopsies Constitute a Robust Biomarker for Cystic Fibrosis Diagnosis and Prognosis

Background Cystic Fibrosis (CF) is caused by ∼1,900 mutations in the CF transmembrane conductance regulator (CFTR) gene encoding for a cAMP-regulated chloride (Cl−) channel expressed in several epithelia. Clinical features are dominated by respiratory symptoms, but there is variable organ involvement thus causing diagnostic dilemmas, especially for non-classic cases. Methodology/Principal Findings To further establish measurement of CFTR function as a sensitive and robust biomarker for diagnosis and prognosis of CF, we herein assessed cholinergic and cAMP-CFTR-mediated Cl− secretion in 524 freshly excised rectal biopsies from 118 individuals, including patients with confirmed CF clinical diagnosis (n = 51), individuals with clinical CF suspicion (n = 49) and age-matched non-CF controls (n = 18). Conclusive measurements were obtained for 96% of cases. Patients with “Classic CF”, presenting earlier onset of symptoms, pancreatic insufficiency, severe lung disease and low Shwachman-Kulczycki scores were found to lack CFTR-mediated Cl− secretion (<5%). Individuals with milder CF disease presented residual CFTR-mediated Cl− secretion (10–57%) and non-CF controls show CFTR-mediated Cl− secretion ≥30–35% and data evidenced good correlations with various clinical parameters. Finally, comparison of these values with those in “CF suspicion” individuals allowed to confirm CF in 16/49 individuals (33%) and exclude it in 28/49 (57%). Statistical discriminant analyses showed that colonic measurements of CFTR-mediated Cl− secretion are the best discriminator among Classic/Non-Classic CF and non-CF groups. Conclusions/Significance Determination of CFTR-mediated Cl− secretion in rectal biopsies is demonstrated here to be a sensitive, reproducible and robust predictive biomarker for the diagnosis and prognosis of CF. The method also has very high potential for (pre-)clinical trials of CFTR-modulator therapies.

Regression of childhood Barrett's esophageal mucosa by antireflux surgery and bipolar electrocoagulation

The authors report a case of a 13-year-old girl with Barretts esophagus who underwent antireflux surgery and was subsequently treated with endoscopic thermal coagulation using bipolar electrocoagulation. Follow-up endoscopy 15 months after completion of the endoscopic therapy showed normal esophageal mucosa without intestinal metaplasia. Longer follow-up is needed to assess the long-term effects of endoscopic treatment of the Barretts mucosa with thermal coagulation, and this procedure should still be considered under investigation.

Clinical and endoscopic outcome after Nissen fundoplication for gastroesophageal reflux disease

CONTEXT The surgical treatment of gastroesophageal reflux disease is indicated in patients with a chronic condition when proton pump inhibitors therapy is ineffective or when symptoms are persistently recurrent. Fundoplication failure occurrence has been detected in some patients and highlights a needing of monitoring esophageal post-surgical condition since that clinical symptoms are not sensitive enough for indicating fundoplication failure. AIMS To identify the frequency of a disrupted wrap in the postoperative period and to evaluate esophageal complications related with gastroesophageal reflux recurrence in children and adolescents. METHODS The study was cross-sectional, prospective and descriptive, including 45 patients (16 months-16.9 years) who had undergone Nissen fundoplication in a school hospital. Twenty six patients (57.8%) were neurologically impaired. Upper gastrointestinal endoscopy was performed in order to determine fundoplication integrity, endoscopic and histopathological esophageal condition. Upper gastrointestinal endoscopies were performed from 12 up to 30 months after surgery. RESULTS Patent wrap was identified in 41 patients (91.1%). Recurrent peptic esophagitis was found in 6 of 45 patients, 2 of which required a second fundoplication and other two had Barrett esophagus. Endoscopic peptic esophagitis was associated with a defective wrap (P = 0.005). Conclusions - Fundoplication was effective for treating esophagitis, even in patients with previous esophageal stenosis. Endoscopic follow up may detect surgery failure in children undergone anti-reflux surgery even in asymptomatic patients.

Thirty Years of Sweat Chloride Testing at One Referral Center

Objective To conduct a descriptive analysis of the sweat test (ST), associating ST results with epidemiological data, CFTR (cystic fibrosis transmembrane conductance regulator) mutations and reasons to indicate the ST, as well as correlating sweat sodium and sweat chloride concentrations in subjects. Methods Retrospective survey and descriptive analysis of 5,721 ST at a university referral center. Results The inclusion of the subjects was based on clinical data related with cystic fibrosis (CF) phenotype. The samples were grouped by (i) sweat chloride concentrations (mEq/L): <30: 3,249/5,277 (61.6%); ≥30 to <60: 1,326/5,277 (25.1%); ≥60: 702/5,277 (13.3%) and (ii) age: (Group A––GA) 0 to <6 months; (Group B––GB) ≥6 months to <18 years; (Group C––GC) ≥18 years. Digestive symptoms showed higher prevalence ratio for the CF diagnosis as well as association between younger age and higher values of sweat chloride, sweat sodium, and chloride/sodium ratio. The indication of ST due to respiratory symptoms was higher in GB and associated with greater age, lower values of sweat chloride, sweat sodium, and chloride/sodium ratio. There was higher prevalence of ST with sweat chloride levels <30 mEq/L in GB, ≥60 mEq/L in GC, and with borderline level in GB. There was positive correlation between sweat sodium and sweat chloride. Sweat chloride/sweat sodium and sweat sodium–sweat chloride indexes showed association with sex, reason for ST indication, and CFTR mutations. Sex alters some values presented in the ST. The number of ST/year performed before and after the newborn screening implementation was the same; however, we observed a higher number of borderlines values. A wide spectrum of CFTR mutation was found. Severe CFTR mutations and F508del/F508del genotype were associated with highest probability of ST chloride levels ≥60 mEq/L, and the absence of CFTR mutations identified was associated with borderline ST and respiratory symptoms. Conclusions ST data showed wide variability dependent on age, sex, reason for examination indication, CFTR mutations, and weight of the collected sweat sample. Sweat sodium concentration is directly correlated with sweat chloride levels and it could be used as a quality parameter.

Evolução clínica e endoscópica após fundoplicatura para tratamento da doença do refluxo gastroesofágico

CONTEXT The surgical treatment of gastroesophageal reflux disease is indicated in patients with a chronic condition when proton pump inhibitors therapy is ineffective or when symptoms are persistently recurrent. Fundoplication failure occurrence has been detected in some patients and highlights a needing of monitoring esophageal post-surgical condition since that clinical symptoms are not sensitive enough for indicating fundoplication failure. AIMS To identify the frequency of a disrupted wrap in the postoperative period and to evaluate esophageal complications related with gastroesophageal reflux recurrence in children and adolescents. METHODS The study was cross-sectional, prospective and descriptive, including 45 patients (16 months-16.9 years) who had undergone Nissen fundoplication in a school hospital. Twenty six patients (57.8%) were neurologically impaired. Upper gastrointestinal endoscopy was performed in order to determine fundoplication integrity, endoscopic and histopathological esophageal condition. Upper gastrointestinal endoscopies were performed from 12 up to 30 months after surgery. RESULTS Patent wrap was identified in 41 patients (91.1%). Recurrent peptic esophagitis was found in 6 of 45 patients, 2 of which required a second fundoplication and other two had Barrett esophagus. Endoscopic peptic esophagitis was associated with a defective wrap (P = 0.005). Conclusions - Fundoplication was effective for treating esophagitis, even in patients with previous esophageal stenosis. Endoscopic follow up may detect surgery failure in children undergone anti-reflux surgery even in asymptomatic patients.

Evaluation of continuous constant current and continuous pulsed current in sweat induction for cystic fibrosis diagnosis

BackgroundThe sweat test (ST) is the gold standard for the diagnosis of cystic fibrosis (CF). However, little is known about sweat induction using different types of currents and waves. In this context, our objective was to develop a device to induce sweat and compare the use of continuous constant current (CCC) and continuous pulsed current (CPC) in individuals with CF and healthy controls.MethodsA prospective cross-sectional study with experimental intervention. The variables of gender, ethnicity, age, and body mass index (BMI) were considered. The method of Gibson and Cooke was used, and the following markers were evaluated: sweat weight, electrical impedance, sufficient sweat amount, and CF diagnosis. Triangular (TPC) or sinusoidal (SPC) pulsed current was applied to the right arm, and CCC was applied to the left arm.ResultsThe study analyzed 260 individuals, 141/213 (54.2%) were female participants, 135/260 (51.9%) were Caucasians. The distribution of individuals by concentration of chloride at the ST was: (CF) 26/260 (10%); (borderlines) 109/260 (41.9%); (healthy) 97/260 (37.3%); (insufficient weight in sweat) 28/260 (10.8%). No association was observed between the sufficient sweat amount to perform the ST when we compared the currents. However, the SPC showed a higher amount of sweat weight. Using Bland and Altman plot considering the agreement between the sweat chloride values achieved from CPC [SPC and TPC] and CCC, there was no proportional bias and mean values are unrelated and only explain less than 8% of the variation. Moreover, TPC presented higher electrical impedance when compared with SPC and CCC. SPC presented lower electrical impedance and higher sweat weight than CCC. Male participants presented lower electrical impedance and higher sweat weight with CCC and TPC, and higher sweat weight with SPC.ConclusionsThe evaluated currents are safe and able to induce and produce sweat in sufficient quantities for the ST. SPC presented lower electrical impedance when compared with other currents. The use of SPC is recommended to induce sweat in patients with sweat problems. Finally, ethnicity, gender, age and BMI did not influence sweat induction at the ST, and no side effect was observed in our study.