Pulsed direct and constant direct currents in the pilocarpine iontophoresis sweat chloride test.

BACKGROUND: The classic sweat test (CST) is the golden standard for cystic fibrosis (CF) diagnosis. Then, our aim was compare the production and volume of sweat, and side effects caused by pulsed direct current (PDC) and constant direct current (CDC). To determine the optimal stimulation time (ST) for the sweat collection. To verify the PDC as CF diagnosis option. METHODS: Prospective study with cross-sectional experimental intervention. Experiment 1 (right arm): PDC and CDC. ST at 10 min and sweat collected at 30 min. Currents of 0.5; 0.75; 1.0 and 1.5 mA and frequencies of 0, 200, 1,000 and 5,000 Hz applied. Experiment 2 (left arm): current of 1.0 mA, ST at 5 and 10 min and sweat collected at 15 and 30 min with frequencies of 0; 200; 1,000 and 5,000 Hz applied Experiments 1 and 2 were performed with current density (CD) from 0.07 to 0.21 mA/cm2. Experiment 3: PDC was used in typical CF patients with two CFTR mutations screened and or with CF diagnosis by rectal biopsy and patients with atypical CF. RESULTS: 48 subjects (79.16% female) with average of 29.54 ± 8.87 years old were enrolled. There was no statistical difference between the interaction of frequency and current in the sweat weight (p = 0.7488). Individually, positive association was achieved between weight sweat and stimulation frequency (p = 0.0088); and current (p = 0.0025). The sweat production was higher for 10 min of stimulation (p = 0.0023). The sweat collection was better for 30 min (p = 0.0019). The skin impedance was not influenced by ST and sweat collection (p > 0.05). The current frequency was inversely associated with the skin impedance (p < 0.0001). The skin temperature measured before stimulation was higher than after (p < 0.0001). In Experiment 3 (29 subjects) the PDC showed better kappa index compared to CDC (0.9218 versus 0.5205, respectively). CONCLUSIONS: The performance of the CST with CDC and PDC with CD of 0.14 to 0.21 mA/cm2 showed efficacy in steps of stimulation and collection of sweat, without side effects. The optimal stimulation time and sweat collection were, respectively, 10 and 30 min.

FACTORS ASSOCIATED WITH A HIGHER NUMBER OF ESOPHAGEAL DILATIONS IN CHILDREN WITH A HISTORY OF ALKALINE INGESTION.

BACKGROUND: Children who experience alkaline injury are at risk for the development of esophageal strictures and the need for esophageal dilations. OBJECTIVE: We aimed to assess predictors for a higher number of esophageal dilatations in children following alkali ingestion. METHODS: Single-center retrospective cohort study including children who underwent esophagogastroduodenoscopy (EGD) after alkali ingestion. Possible predictive factors for the need for esophageal dilatations were evaluated. RESULTS: A total of 34 patients were included, and 19 were female (55.9%). The median age at the time of the accidents was 20.6 months (IQR 15-30.7). All alkali ingestions were accidental, in all cases involving liquid products, and most (24/34; 70%) occurred at the child's home. Homemade liquid soap was the agent in half of the cases. The most frequently reported symptom at presentation was vomiting (22/34, 64.7%). The median follow-up time was 3.2 years (IQR 1.1-7.4). On follow-up, the median number of esophageal dilatations required for these patients was 12.5 (IQR 0-34). Among demographic factors, male gender (P=0.04), ingestion of homemade products (P<0.01), and accidents happening outside of the household environment (P=0.02) were associated with a greater number of esophageal dilations on follow-up. An endoscopic classification Zargar of 2B or higher (P=0.03), the presence of stricture at the time of the second EGD (P=0.01), and gastroesophageal reflux disease (GERD) as a late complication (P=0.01) were also associated with a greater number of esophageal dilations on long term follow-up. CONCLUSION: Beyond the endoscopic classification severity - a well-known risk factor for the strictures after alkali ingestions, we found that male gender, accidents with homemade products, and accidents occurring outside the household environment were significantly associated with a greater number of esophageal dilatations in the long-term follow-up of children following alkali ingestion.

Combined multi-channel intraluminal impedance measurement and pHmetry in the detection of gastroesophageal reflux disease in children with cystic fibrosis.

OBJECTIVE: To assess the prevalence of GERD exclusively by means of multichannel intraluminal impedanciometry associated with pH monitoring (MIIpH) and compare it with respiratory symptoms in children with CF. To compare MIIpH with pHmetry alone to perform GERD diagnosis. METHODS: An analytical cross-sectional study was conducted with children diagnosed with CF who underwent MIIpH. Clinical and laboratory markers, including respiratory and digestive symptoms, were used for comparative analyses. High-resolution chest computed tomography was performed on patients with symptoms of chronic lung disease. Severity was classified according to the Bhalla score. RESULTS: A total of 29 children < 10 yo (18 girls) were evaluated; 19 of whom with physiological GER and 10 with GERD. Of the children with GERD, seven had predominantly acid GER, two acid+non-acid GER, and one non-acid GER. Three patients had GERD diagnosed only by MIIpH. Bhalla scores ranged from seven to 17.75 with no significant relationship with GERD. The number of pulmonary exacerbations was associated with a decrease in esophageal clearance regardless of the position in pHmetry and MIIpH. CONCLUSIONS: The prevalence of GERD was 34% in children with CF. There was no association between respiratory disease severity and GER types. MIIpH detected 30% more patients with GERD than pHmetry.

Brazilian Guidelines for Nutrition in Cystic Fibrosis.

OBJECTIVE: To develop a scientific consensus on nutrition in cystic fibrosis. METHODS: Sixteen coordinators elaborated relevant questions on nutritional therapy in cystic fibrosis, which were divided into six sections: nutritional assessment, nutritional recommendations, nutritional intervention, dietary counseling, special situations and enzyme replacement, and gastrointestinal manifestations. Two to three specialists in the field were responsible for each section and obtaining answers formulated based on standardized bibliographic searches. The available literature was searched in the PubMed®/MEDLINE database, after training and standardization of search strategies, to write the best level of evidence for the questions elaborated. Issues related to disagreement were discussed until a consensus was reached among specialists, based on the current scientific literature. RESULTS: Forty-two questions were prepared and objectively answered, resulting in a consensus of nutritional therapy in cystic fibrosis. CONCLUSION: This work enabled establishing a scientific consensus for nutritional treatment of cystic fibrosis patients.

Elevated IgA and IL-10 levels in very-early-onset inflammatory bowel disease secondary to IL-10 receptor deficiency.

OBJECTIVE: To report two patients with very-early-onset inflammatory bowel disease (VEOIBD) secondary to interleukin-10 receptor (IL-10R) mutations, explore immunophenotyping data and plasma cytokine profile on these cases compared to healthy controls, and describe the phenotype of IL-10/IL-10R mutations based on a literature review. CASE DESCRIPTION: We report on two female infants referred to our tertiary center at the age of ten months, with severe colonic and perianal disease, as well as significant malnutrition, who had shown limited response to usual inflammatory bowel disease (IBD) therapy agents. In the first case, whole-exome sequencing (WES) revealed a homozygous (c.537G>A/p.T179T) mutation in exon 4 of the IL-10RA gene, while in the second patient, compound heterozygosity was identified, also in the IL-10RA gene (chr11:117.859.199 variant A>G/p.Tyr57Cys and chr11: 117.860.335 variant G>T/p.Val123Leu). Both patients underwent hematopoietic cell transplantation (HCT). Immunological work-up of these patients revealed increased IL-10 plasma levels and increased IgA. COMMENTS: Our case reports disclose novel findings on plasma cytokine profile in IL-10R deficiency, and we describe the severe phenotype of IL-10/IL-10R deficiency that should be recognized by physicians.

PEUTZ-JEGHERS SYNDROME IN RESOURCE-LIMITED SCENARIO.

BACKGROUND: Peutz-Jeghers Syndrome (PJS) is a rare, autosomal dominant disease, caused by deletions in the chromosome 19p33.3/ gene LKB1/STK11. These mutations inactivate a serine/threonine kinase and predispose to carcinogenesis. In PJS, tumors of the gastrointestinal, testicles, pulmonary, breast, pancreas, uterus and ovaries can be found. OBJECTIVE: To evaluate demographics, clinical presentation and complication/outcomes of pediatric patients presenting with Peutz-Jeghers syndrome (PJS), as well as to present and discuss management in the context of limited resources. METHODS: We conducted a retrospective chart review of a cohort of six patients, who were diagnosed and/or followed at the Clinics Hospital, University of Campinas - Sao Paulo/Brazil, between 2000 and 2018. Data analyzed included gender, age of presentation, age of diagnosis, family history, PJS complications. RESULTS: Median age of diagnosis of 6.7 years, with a mean time of follow-up of 8.1 years. Mucocutaneous pigmentation was universally present. Half of the patients had a known family history at the time of diagnosis. On follow up, intestinal intussusception was documented in four out of six patients, in most (three), in different locations and in multiple occasions. The active investigation of siblings and parents of the index case led to the diagnosis of three first-degree relatives in the present case series. CONCLUSION: In this first pediatric PJS Brazilian case series, we report a wide spectrum of PJS manifestations and complications. In a resource limited scenario, despite limitations for the surveillance of complications, the relative frequency of complications was not higher than historically reported.

Distal intestinal obstruction syndrome: a diagnostic and therapeutic challenge in cystic fibrosis.

OBJECTIVE: To evaluate the demographics, genotype, and clinical presentation of pediatric patients presenting with distal intestinal obstruction syndrome (DIOS), and factors associated with DIOS recurrence. METHODS: Case series of ten patients (median age 13.2 years), followed-up in a reference center, retrospectively assessed. Data analyzed included age, gender, cystic fibrosis genotype, meconium ileus at birth, hydration status, pulmonary exacerbation, Pseudomonas aeruginosa colonization, pancreatic insufficiency (PI), body mass index (BMI) at the episodes, clinical manifestations of DIOS, imaging studies performed, acute management of DIOS, maintenance therapy, and recurrence on follow-up. RESULTS: All patients had two positive sweat chloride tests, and nine of ten also had genotype study. The most common genotype identified was homozygosis for the delta F508 mutation. In seven cases, a previous history of meconium ileus was reported. All patients had pancreatic insufficiency. Diagnosis of DIOS was based on clinical and imaging findings. Of the total number of episodes, 85% were successfully managed with oral osmotic laxatives and/or rectal therapy (glycerin enema or saline irrigation). Recurrence was observed in five of ten patients. CONCLUSION: In this first report of pediatric DIOS in South America, the presence of two risk factors for DIOS occurrence was universal: pancreatic insufficiency and severe genotype. Medical history of meconium ileus at birth was present in most patients, as well as in the subgroup with DIOS recurrence. The diagnosis relied mainly on the clinical presentation and on abdominal imaging. The practices in the management of episodes varied, likely reflecting changes in the management of this syndrome throughout time.

Fatores associados a um maior número de dilatações esofágicas em crianças com história de ingestão alcalina / Factors associated with a higher number of esophageal dilations in children with a history of alkaline ingestion

ABSTRACT Background: Children who experience alkaline injury are at risk for the development of esophageal strictures and the need for esophageal dilations. Objective: We aimed to assess predictors for a higher number of esophageal dilatations in children following alkali ingestion. Methods: Single-center retrospective cohort study including children who underwent esophagogastroduodenoscopy (EGD) after alkali ingestion. Possible predictive factors for the need for esophageal dilatations were evaluated. Results: A total of 34 patients were included, and 19 were female (55.9%). The median age at the time of the accidents was 20.6 months (IQR 15-30.7). All alkali ingestions were accidental, in all cases involving liquid products, and most (24/34; 70%) occurred at the child's home. Homemade liquid soap was the agent in half of the cases. The most frequently reported symptom at presentation was vomiting (22/34, 64.7%). The median follow-up time was 3.2 years (IQR 1.1-7.4). On follow-up, the median number of esophageal dilatations required for these patients was 12.5 (IQR 0-34). Among demographic factors, male gender (P=0.04), ingestion of homemade products (P<0.01), and accidents happening outside of the household environment (P=0.02) were associated with a greater number of esophageal dilations on follow-up. An endoscopic classification Zargar of 2B or higher (P=0.03), the presence of stricture at the time of the second EGD (P=0.01), and gastroesophageal reflux disease (GERD) as a late complication (P=0.01) were also associated with a greater number of esophageal dilations on long term follow-up. Conclusion: Beyond the endoscopic classification severity - a well-known risk factor for the strictures after alkali ingestions, we found that male gender, accidents with homemade products, and accidents occurring outside the household environment were significantly associated with a greater number of esophageal dilatations in the long-term follow-up of children following alkali ingestion.

RESUMO Contexto: Crianças que sofrem lesões cáusticas correm alto risco de desenvolver estenose esofágica e necessidade de dilatações esofágicas. Objetivo: Objetivamos avaliar preditores de necessidade de maior número de dilatações esofágicas em crianças, após uma ingestão cáustica. Métodos: Estudo de coorte retrospectivo de centro único incluindo crianças submetidas a esofagogastroduodenoscopia (EGD) após ingestão cáustica. Foram avaliados possíveis fatores preditivos para a necessidade de dilatações esofágicas. Resultados: Foram incluídos 34 pacientes, 19 do sexo feminino (55,9%). A idade mediana no momento dos acidentes foi de 20,6 meses (IQR 15-30,7). Todas as ingestões cáusticas foram incidentais, de substâncias líquidas, e a maioria dos acidentes (24/34; 70%) ocorreu no domicílio da criança. Em metade dos casos, a substância ingerida foi um sabão caseiro. O sintoma mais reportado na apresentação foi vômito (22/34 -64,7%). O tempo médio de acompanhamento foi de 3,2 anos (IQR 1,1- 7,4). No seguimento, o número médio de dilatações esofágicas necessárias foi de 12,5 (IQR 0-34). Entre os fatores demográficos, o sexo masculino (P=0,04), acidentes com produtos caseiros (P=<0,01) e a localização do acidente fora do ambiente domiciliar (P=0,02) foram associados a um maior número de dilatações esofágicas no seguimento. A classificação endoscópica Zargar 2B ou mais (P=0,03), a presença de estenose na segunda EGD (P=0,01) e a DRGE como complicação tardia (P=0,01) também se associaram a maior número de dilatações esofágicas no acompanhamento a longo prazo. Conclusão: Além da gravidade da classificação endoscópica - fator de risco bem conhecido para as estenoses após ingestão de cáusticos, observamos que o sexo masculino, os acidentes com produtos caseiros e os acidentes ocorridos fora do ambiente doméstico foram fatores significativamente associados a um maior número de dilatações esofágicas em acompanhamento em longo prazo de crianças após ingestão de soda cáustica.

Combined multi-channel intraluminal impedance measurement and pHmetry in the detection of gastroesophageal reflux disease in children with cystic fibrosis

Abstract Objective To assess the prevalence of GERD exclusively by means of multichannel intraluminal impedanciometry associated with pH monitoring (MIIpH) and compare it with respiratory symptoms in children with CF. To compare MIIpH with pHmetry alone to perform GERD diagnosis. Methods An analytical cross-sectional study was conducted with children diagnosed with CF who underwent MIIpH. Clinical and laboratory markers, including respiratory and digestive symptoms, were used for comparative analyses. High-resolution chest computed tomography was performed on patients with symptoms of chronic lung disease. Severity was classified according to the Bhalla score. Results A total of 29 children < 10 yo (18 girls) were evaluated; 19 of whom with physiological GER and 10 with GERD. Of the children with GERD, seven had predominantly acid GER, two acid+non-acid GER, and one non-acid GER. Three patients had GERD diagnosed only by MIIpH. Bhalla scores ranged from seven to 17.75 with no significant relationship with GERD. The number of pulmonary exacerbations was associated with a decrease in esophageal clearance regardless of the position in pHmetry and MIIpH. Conclusions The prevalence of GERD was 34% in children with CF. There was no association between respiratory disease severity and GER types. MIIpH detected 30% more patients with GERD than pHmetry.

MAST CELLS DISTINGUISH EOSINOPHILIC ESOPHAGITIS IN PEDIATRIC PATIENTS.

BACKGROUND:: Mast cells exert a substantial role in gastrointestinal allergic diseases. Therefore, it is reasonable to presume that mast cell may aid diagnosis in eosinophilic gastroenteropathy. OBJECTIVE:: To evaluate whether mast cell count in the esophageal epithelium can discriminate eosinophilic esophagitis, proton-pump inhibitor (PPI)-responsive eosinophilic esophagitis and gastroesophageal reflux esophagitis. METHODS:: Retrospectively we reviewed the files of 53 consecutive patients (age: 7.8 years; range: 8-14 years) with definitive diagnose established during clinical follow up in a universitary outpatient clinic as follow: eosinophilic esophagitis (N=23), PPI-responsive eosinophilic esophagitis (N=15) and gastroesophageal reflux esophagitis (N=15). Eosinophil count in the esophageal epithelium in slides stained with H-E was reviewed and immunohistochemistry for mast cell tryptase was performed. RESULTS:: Count of eosinophils/high-power field (HPF) higher than 15 were found in 14 out of 15 reflux esophagitis patients. The mean count of eosinophils/HPF was similar in eosinophilic esophagitis patients and in those with PPI-responsive eosinophilic esophagitis (42 and 39 eosinophils/HPF, respectively, P=0.47). Values of mast cell tryptase (+) were higher in eosinophilic esophagitis [median: 25 mast cells/HPF; range (17-43) ] and in PPI-responsive eosinophilic esophagitis patients [25 (16-32) ], compared to reflux esophagitis [4 (2-14) ], P<0.001. There was no difference between the mean count of mast cells/HPF in the esophageal epithelium of eosinophilic esophagitis patients and PPI-responsive eosinophilic esophagitis patients, respectively, 26 and 24 mast cells/HPF, P=0.391. CONCLUSION:: Tryptase staining of mast cells differentiates eosinophilic esophagitis from reflux esophagitis.

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.

Elevated IgA and IL-10 levels in very-early-onset inflammatory bowel disease secondary to IL-10 receptor deficiency / Níveis elevados de IgA e IL-10 na doença inflamatória intestinal de início muito precoce secundária à deficiência do receptor de IL-10

ABSTRACT Objective: To report two patients with very-early-onset inflammatory bowel disease (VEOIBD) secondary to interleukin-10 receptor (IL-10R) mutations, explore immunophenotyping data and plasma cytokine profile on these cases compared to healthy controls, and describe the phenotype of IL-10/IL-10R mutations based on a literature review. Case description: We report on two female infants referred to our tertiary center at the age of ten months, with severe colonic and perianal disease, as well as significant malnutrition, who had shown limited response to usual inflammatory bowel disease (IBD) therapy agents. In the first case, whole-exome sequencing (WES) revealed a homozygous (c.537G>A/p.T179T) mutation in exon 4 of the IL-10RA gene, while in the second patient, compound heterozygosity was identified, also in the IL-10RA gene (chr11:117.859.199 variant A>G/p.Tyr57Cys and chr11: 117.860.335 variant G>T/p.Val123Leu). Both patients underwent hematopoietic cell transplantation (HCT). Immunological work-up of these patients revealed increased IL-10 plasma levels and increased IgA. Comments: Our case reports disclose novel findings on plasma cytokine profile in IL-10R deficiency, and we describe the severe phenotype of IL-10/IL-10R deficiency that should be recognized by physicians.

RESUMO Objetivo: Relatar os casos de duas pacientes com doença inflamatória intestinal de início muito precoce (em inglês VEOIBD) secundária a mutações do receptor de interleucina 10 (IL-10R), explorar dados de imunofenotipagem e perfil de citocinas plasmáticas nesses casos em comparação com indivíduos saudáveis e descrever o fenótipo de mutações IL-10/IL-10R com base em uma revisão da literatura. Descrição do caso: Duas lactentes do sexo feminino foram encaminhadas ao nosso centro terciário, ambas com dez meses no momento do encaminhamento, com doença colônica e perianal grave, bem como desnutrição significativa, tendo uma resposta limitada aos agentes de terapia usuais de doença inflamatória intestinal (DII). No primeiro caso, o sequenciamento completo do exoma revelou mutação homozigótica (c. 537G>A/p.T179T) no exon 4 do gene IL-10RA, enquanto no segundo caso heterozigosidade composta foi identificada também no gene IL-10RA [chr11: 117.859.199 - variante A>G/p.Tyr57Cys e chr11: 117.860.335 - variante G>T/ p.Val123Leu]. Ambas as pacientes foram submetidas a Transplante de Células-Tronco Hematopoiéticas. A investigação imunológica das pacientes revelou aumento dos níveis plasmáticos de IL-10 e aumento da IgA. Comentários: Nossos relatos de casos descrevem novos achados no perfil de citocinas plasmáticas na deficiência de IL-10R, e relatamos o fenótipo grave da deficiência de IL-10/IL-10R que deve ser reconhecido pelos médicos.

Brazilian Guidelines for Nutrition in Cystic Fibrosis

ABSTRACT Objective To develop a scientific consensus on nutrition in cystic fibrosis. Methods Sixteen coordinators elaborated relevant questions on nutritional therapy in cystic fibrosis, which were divided into six sections: nutritional assessment, nutritional recommendations, nutritional intervention, dietary counseling, special situations and enzyme replacement, and gastrointestinal manifestations. Two to three specialists in the field were responsible for each section and obtaining answers formulated based on standardized bibliographic searches. The available literature was searched in the PubMed®/MEDLINE database, after training and standardization of search strategies, to write the best level of evidence for the questions elaborated. Issues related to disagreement were discussed until a consensus was reached among specialists, based on the current scientific literature. Results Forty-two questions were prepared and objectively answered, resulting in a consensus of nutritional therapy in cystic fibrosis. Conclusion This work enabled establishing a scientific consensus for nutritional treatment of cystic fibrosis patients.

Quality of sweat test (ST) based on the proportion of sweat sodium (Na) and sweat chloride (Cl) as diagnostic parameter of cystic fibrosis: are we on the right way?

BACKGROUND: To assess the quality of sweat test (ST) based on the proportion of sweat sodium and sweat chloride as diagnostic parameter of cystic fibrosis (CF). METHODS: A retrospective study of 5,721 sweat samples and subsequent descriptive analysis were carried out. The test was considered "of good quality" (correct) when: (i) sweat chloride was lower than 60 mEq/L, and sweat sodium was higher than sweat chloride; (ii) sweat chloride was higher than 60 mEq/L, and sweat sodium was lower than sweat chloride. RESULTS: The study included 5,692/5,721 sweat samples of ST which had been requested due to clinical presentations compatible with CF and/or neonatal screenings with altered immunoreactive trypsinogen values. Considering the proportion of sweat sodium and sweat chloride as ST quality parameter, the test was performed correctly in 5,023/5,692 (88.2 %) sweat samples. The sweat chloride test results were grouped into four reference ranges for chloride (i) chloride < 30 mEq/L: 3,651/5,692 (64.1 %); (ii) chloride ≥ 30 mEq/L to < 40 mEq/L: 652/5,692 (11.5 %); (iii) ≥ 40 mEq/L to < 60 mEq/L: 673/5,692 (11.8 %); (iv) ≥ 60 mEq/L: 716/5,692 (12.6 %). In the comparative analysis, there was no association between ST quality and: (i) symptoms to indicate a ST [respiratory (p = 0.084), digestive (p = 0.753), nutritional (p = 0.824), and others (p = 0.136)], (ii) sweat weight (p = 0.416). However, there was a positive association with: (i) gender, (ii) results of ST (p < 0.001), (iii) chloride/sodium ratio (p < 0.001), (iv) subject's age at the time of ST [grouped according to category (p < 0.001) and numerical order (p < 0.001)]. For the subset of 169 patients with CF and two CFTR mutations Class I, II and/or III, in comparative analysis, there was a positive association with: (i) sweat chloride/sodium ratio (p < 0.001), (ii) sweat chloride values (p = 0.047), (iii) subject's age at the time of the ST grouped by numerical order (p = 0.001). CONCLUSIONS: Considering that the quality of ST can be assessed by levels of sweat sodium and sweat chloride, an increasing number of low-quality tests could be observed in our sweat samples. The quality of the test was associated with important factors, such as gender, CF diagnosis, and subjects' age.

Manejo da síndrome de Peutz-Jeghers no contexto de recursos limitados / Peutz-jeghers syndrome in resource-limited scenario

ABSTRACT BACKGROUND: Peutz-Jeghers Syndrome (PJS) is a rare, autosomal dominant disease, caused by deletions in the chromosome 19p33.3/ gene LKB1/STK11. These mutations inactivate a serine/threonine kinase and predispose to carcinogenesis. In PJS, tumors of the gastrointestinal, testicles, pulmonary, breast, pancreas, uterus and ovaries can be found. OBJECTIVE: To evaluate demographics, clinical presentation and complication/outcomes of pediatric patients presenting with Peutz-Jeghers syndrome (PJS), as well as to present and discuss management in the context of limited resources. METHODS: We conducted a retrospective chart review of a cohort of six patients, who were diagnosed and/or followed at the Clinics Hospital, University of Campinas - Sao Paulo/Brazil, between 2000 and 2018. Data analyzed included gender, age of presentation, age of diagnosis, family history, PJS complications. RESULTS: Median age of diagnosis of 6.7 years, with a mean time of follow-up of 8.1 years. Mucocutaneous pigmentation was universally present. Half of the patients had a known family history at the time of diagnosis. On follow up, intestinal intussusception was documented in four out of six patients, in most (three), in different locations and in multiple occasions. The active investigation of siblings and parents of the index case led to the diagnosis of three first-degree relatives in the present case series. CONCLUSION: In this first pediatric PJS Brazilian case series, we report a wide spectrum of PJS manifestations and complications. In a resource limited scenario, despite limitations for the surveillance of complications, the relative frequency of complications was not higher than historically reported.

RESUMO CONTEXTO: A síndrome de Peutz-Jeghers (SPJ) é uma doença autossômica dominante rara, causada por deleções no cromossomo 19p33.3/gene LKB1/STK11. Essas mutações inativam uma serina/treonina quinase e predispõem à carcinogênese. Na SPJ, podem ser encontrados tumores do trato gastrointestinal, testicular, pulmonar, de mama, de pâncreas, de útero e de ovários. OBJETIVO: Avaliar dados demográficos, apresentação clínica e complicações de pacientes pediátricos que se apresentam com SPJ, além de apresentar e discutir o manejo no contexto de recursos limitados. MÉTODOS: Realizamos uma revisão retrospectiva de prontuários de uma coorte de seis pacientes, diagnosticados e/ou acompanhados no Hospital das Clínicas da Universidade de Campinas - São Paulo, Brasil, entre 2000 e 2018. Os dados analisados incluíram sexo, idade de apresentação, idade do diagnóstico, história familiar, complicações da SPJ. RESULTADOS: Idade média de diagnóstico de 6,7 anos, com tempo médio de seguimento de 8,1 anos. A pigmentação mucocutânea estava universalmente presente. Metade dos pacientes tinha um histórico familiar conhecido no momento do diagnóstico. Intussuscepção intestinal foi observada em quatro dos seis pacientes durante o período de acompanhamento, sendo que em três ocorreram vários episódios em diferentes múltiplas localizações. A investigação ativa de irmãos e pais do caso-índice levou ao diagnóstico de três parentes de primeiro grau na presente série de casos. CONCLUSÃO: Nesta primeira série de casos brasileiros de SPJ pediátrica, relatamos um amplo espectro de manifestações e complicações da SPJ. Em um contexto de recursos limitados, apesar das limitações para a vigilância de complicações, a frequência relativa de complicações não foi maior do que o relatado historicamente.

Distal intestinal obstruction syndrome: a diagnostic and therapeutic challenge in cystic fibrosis / Síndrome da obstruc¸ão intestinal distal: um desafio diagnóstico e terapêutico na fibrose cística

Abstract Objective: To evaluate the demographics, genotype, and clinical presentation of pediatric patients presenting with distal intestinal obstruction syndrome (DIOS), and factors associated with DIOS recurrence. Methods: Case series of ten patients (median age 13.2 years), followed-up in a reference center, retrospectively assessed. Data analyzed included age, gender, cystic fibrosis genotype, meconium ileus at birth, hydration status, pulmonary exacerbation, Pseudomonas aeruginosa colonization, pancreatic insufficiency (PI), body mass index (BMI) at the episodes, clinical manifestations of DIOS, imaging studies performed, acute management of DIOS, maintenance therapy, and recurrence on follow-up. Results: All patients had two positive sweat chloride tests, and nine of ten also had genotype study. The most common genotype identified was homozygosis for the delta F508 mutation. In seven cases, a previous history of meconium ileus was reported. All patients had pancreatic insufficiency. Diagnosis of DIOS was based on clinical and imaging findings. Of the total number of episodes, 85% were successfully managed with oral osmotic laxatives and/or rectal therapy (glycerin enema or saline irrigation). Recurrence was observed in five of ten patients. Conclusion In this first report of pediatric DIOS in South America, the presence of two risk factors for DIOS occurrence was universal: pancreatic insufficiency and severe genotype. Medical history of meconium ileus at birth was present in most patients, as well as in the subgroup with DIOS recurrence. The diagnosis relied mainly on the clinical presentation and on abdominal imaging. The practices in the management of episodes varied, likely reflecting changes in the management of this syndrome throughout time.

Resumo Objetivo: Avaliar os dados demográficos, o genótipo e o quadro clínico de pacientes pediátricos que apresentam síndrome da obstrução intestinal distal (DIOS) e os fatores associados à recidiva da DIOS. Métodos: Casuística de 10 pacientes (média de 13,2 anos) monitorados em um centro de referência e avaliados de forma retroativa. Os dados analisados incluíram idade, sexo, genótipo da fibrose cística, íleo meconial no nascimento, estado de hidratação, exacerbação pulmonar, colonização por Pseudomonas aeruginosa, insuficiência pancreática (IP), IMC nos episódios, manifestações clínicas da DIOS, estudos de diagnóstico por imagem realizados, manejo agudo da DIOS, terapia de manutenção e recidiva no acompanhamento. Resultados: Todos os pacientes apresentaram dois exames de cloreto no suor positivos e 09/10 também apresentaram estudo do genótipo. O genótipo mais comum identificado foi a homozigose da mutação delta F508. Em sete casos foi mencionado um histórico de íleo meconial. Todos os pacientes apresentaram insuficiência pancreática. O diagnóstico da DIOS teve como base achados clínicos e de imagem; 85% do número total de episódios foram tratados com sucesso com laxantes osmóticos orais e/ou terapia retal (enema de glicerina ou irrigação salina). A recidiva foi observada em 5 de 10 pacientes. Conclusão: Neste primeiro relatório da DIOS pediátrica na América do Sul, a presença de dois fatores de risco na ocorrência da DIOS foi universal: insuficiência pancreática e genótipo associado a doença grave. O histórico de íleo meconial no nascimento esteve presente na maioria dos pacientes, bem como no subgrupo com recidiva da DIOS. O diagnóstico dependeu principalmente do quadro clínico e do diagnóstico por imagem abdominal. As práticas de manejo de episódios variaram, provavelmente refletiram as mudanças no tratamento dessa síndrome ao longo do tempo.

Growth assessment in children with extra-hepatic portal vein obstruction and portal hypertension.

BACKGROUND: Several studies carried out to examine the growth of children with extra-hepatic portal vein obstruction and portal hypertension have reported a variety of findings. AIM: To assess anthropometric indices in children with portal hypertension due to extra-hepatic portal vein obstruction and who were treated by endoscopic variceal sclerotherapy. METHODS: Anthropometric data were obtained retrospectively from the medical records of 24 patients who had been followed for 3.8 +/- 2.5 years at the Pediatric Gastroenterology Outpatient Clinic of the University Hospital, Campinas, SP, Brazil. The mean Z scores of weight for age, height for age and body mass index at diagnosis and at the last consultation were compared to reference data of the National Center for Health Statistics. The two recordings were compared to assess the long-term effect of the condition. RESULTS: The mean Z scores at diagnosis and at the last follow-up visit were all within normal ranges when compared to the reference population, with the following respective values: weight for age, 0.042 +/- 1.09 and 0.132 +/- 1.29; height for age, 0.200 +/- 1.04 and 0.466 +/- 1.24, and body mass index, -0.223 +/- 0.98 and -0.198 +/- 0.98. In addition, there were no significant differences between the Z score values obtained in the two recordings. CONCLUSION: Portal hypertension due to extra-hepatic portal vein obstruction was not associated with growth impairment in the group of children studied.

Trajetória profissional de egressos do curso de Medicina da Universidade de Campinas (Unicamp), São Paulo, Brasil: o olhar do ex-aluno na avaliação do programa / Trayectoria profesional de egresados del curso de Medicina da Universidad de Campinas, São Paulo, Brasil: la mirada del ex-alumno en la evaluación del programa / Professional trajectory of medical course alumni from from Campinas University, São Paulo, Brazil: graduates' point of view in evaluating the course

A Faculdade de Ciências Médicas da Unicamp implantou uma ampla reforma curricular, que antecedeu as Diretrizes Curriculares Nacionais (DCN) de 2001. Analisou-se a trajetória profissional e o impacto da reforma curricular na formação pela percepção dos egressos. Alunos concluintes de 1991-2005 compuseram o grupo pré-reforma e os de 2006-2012, o grupo pós-reforma, que receberam um questionário semiestruturado on-line por e-mail e redes sociais. Obtiveram-se 213 (15,8%) respostas do grupo pré e 126 (16,1%) do pós-reforma. Os dados apontaram pouca dispersão geográfica dos ex-alunos, ocupação de 2,4 postos de trabalho por médico, entendimento da residência como necessária, maior frequência a cursinhos preparatórios no grupo pós-reforma e sugestão de inclusão de administração/gestão em saúde no currículo. A integração entre áreas básicas/clínicas apresentou significante melhora pós-reforma. A percepção sobre a graduação foi altamente positiva. O estudo contribuiu para implantar o acompanhamento sistemático de egressos no curso de Medicina.(AU)

La Facultad de Ciencias Médicas de Unicamp implantó una amplia reforma curricular que antecedió a las directrices curriculares nacionales de 2001. Se analizó la trayectoria profesional y el impacto de la reforma curricular en la formación a partir de la percepción de los egresados. Alumnos concluyentes de la promoción 1991-2005 compusieron el grupo pre-reforma y los de 2006-2012 el grupo post-reforma, recibiendo un cuestionario semi-estructurado, on line, por e-mail y redes sociales. Se obtuvieron 213 (15,8%) respuestas del grupo pre-reforma y 126 (16,1%) del post-reforma. Se encontró poca dispersión geográfica de los ex-alumnos, ocupación de 2,4 puestos de trabajo/médico, comprensión de la residencia como necesaria, mayor frecuencia a cursos preparatorios en el grupo post-reforma y sugerencia de inclusión de administración/gestión en salud en el currículo. La integración entre áreas básicas/clínicas presentó una mejora significativa post-reforma. La percepción sobre la graduación fue altamente positiva. El estudio contribuyó para implantar el acompañamiento sistemático de egresados en el curso de Medicina.(AU)

The School of Medical Sciences of UNICAMP implemented a new curriculum in 2001, predating the national guidelines. This study analyzed the professional trajectory and the new curriculum's impact. Graduates from 1991 to 2005 were grouped in the pre-curricular renovation group, and those from 2006 to 2012 in the post-group. A semi-structured survey was sent through e-mail and social media. There were 213 (15.8%) answers from pre-renovation group and 126 (16.1%) from post. Data showed low geographic dispersion of alumni, 2.4 work posts per physician, residency as a necessary complementation, suggestions for curricular inclusion of management issues and higher frequency of preparatory courses for residency in post-renovation group. There are signs of better integration between basic and clinical areas after the reform. Alumni showed positive perceptions regarding their undergraduate course. The study contributes to the implementation of systematic follow-up of graduates.(AU)

Mastócitos discriminam esofagite eosinofílica em pacientes pediátricos / Mast cells distinguish eosinophilic esophagitis in pediatric patients

ABSTRACT BACKGROUND: Mast cells exert a substantial role in gastrointestinal allergic diseases. Therefore, it is reasonable to presume that mast cell may aid diagnosis in eosinophilic gastroenteropathy. OBJECTIVE: To evaluate whether mast cell count in the esophageal epithelium can discriminate eosinophilic esophagitis, proton-pump inhibitor (PPI)-responsive eosinophilic esophagitis and gastroesophageal reflux esophagitis. METHODS: Retrospectively we reviewed the files of 53 consecutive patients (age: 7.8 years; range: 8-14 years) with definitive diagnose established during clinical follow up in a universitary outpatient clinic as follow: eosinophilic esophagitis (N=23), PPI-responsive eosinophilic esophagitis (N=15) and gastroesophageal reflux esophagitis (N=15). Eosinophil count in the esophageal epithelium in slides stained with H-E was reviewed and immunohistochemistry for mast cell tryptase was performed. RESULTS: Count of eosinophils/high-power field (HPF) higher than 15 were found in 14 out of 15 reflux esophagitis patients. The mean count of eosinophils/HPF was similar in eosinophilic esophagitis patients and in those with PPI-responsive eosinophilic esophagitis (42 and 39 eosinophils/HPF, respectively, P=0.47). Values of mast cell tryptase (+) were higher in eosinophilic esophagitis [median: 25 mast cells/HPF; range (17-43) ] and in PPI-responsive eosinophilic esophagitis patients [25 (16-32) ], compared to reflux esophagitis [4 (2-14) ], P<0.001. There was no difference between the mean count of mast cells/HPF in the esophageal epithelium of eosinophilic esophagitis patients and PPI-responsive eosinophilic esophagitis patients, respectively, 26 and 24 mast cells/HPF, P=0.391. CONCLUSION: Tryptase staining of mast cells differentiates eosinophilic esophagitis from reflux esophagitis.

RESUMO CONTEXTO: Os mastócitos detêm papel fundamental na resposta imuno-alérgica gastrintestinal. Assim, é razoável admitir que essas células sejam úteis no diagnóstico diferencial das gastroenteropatias eosinofílicas. OBJETIVO: Determinar se a análise quantitativa de mastócitos na mucosa esofágica permite discernir esofagite eosinofílica, esofagite eosinofílica responsiva ao inibidor de bomba de prótons e esofagite péptica por doença de refluxo gastroesofágico. MÉTODOS: Revisamos retrospectivamente os prontuários 53 crianças (idade: 7,8 anos; variação: 8-14 anos), atendidas consecutivamente, num serviço terciário e cujos diagnósticos definitivos estabelecidos após seguimento clínico foram esofagite eosinofílica (N=23), esofagite eosinofílica responsiva ao inibidor de bomba de prótons (N=15) e esofagite péptica por doença de refluxo gastroesofágico (N=15). As amostras histológicas foram revisadas quanto à contagem de eosinófilos na coloração de H-E e processadas para imunoistoquímica da triptase de mastócitos. RESULTADOS: Valores de eosinófilos/campo de maior aumento (CMA; 400X) >15 foram encontrados em 14 dos 15 pacientes com refluxo gastroesofágico. A média de eosinófilos/CMA foi similar nos pacientes com esofagite eosinofílica e com esofagite eosinofílica responsiva ao inibidor de bomba de prótons, respectivamente, 42 e 39 eosinófilos/CMA, P=0,47). Os valores de mastócitos triptase (+) foram superiores no epitélio esofágico dos pacientes com esofagite eosinofílica [mediana: 25 mastócitos/CMA; variação (17- 43) ] e na esofagite eosinofílica responsiva ao inibidor de bomba de prótons [25 (16-32) ], comparados aos pacientes com refluxo gastroesofágico [4(2-14) ], P<0,001. Não houve diferença entre a média de mastócitos/CMA nos pacientes com esofagite eosinofílica comparados aos com esofagite eosinofílica responsiva ao inibidor de bomba de prótons, respectivamente, 26 e 24 mastócitos/CMA, P=0,391. CONCLUSÃO: A coloração para mastócitos pela imunoistoquímica da triptase diferencia as esofagites eosinofílicas da esofagite péptica.

[Clinical and endoscopic outcome after Nissen fundoplication for gastroesophageal reflux disease]. / 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.