Chronic Pancreatitis: Pediatric and Adult Cohorts Show Similarities in Disease Progress Despite Different Risk Factors.
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SUBMITTER: Schwarzenberg SJ
PROVIDER: S-EPMC6492264 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
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Project description:BackgroundFew attempts have been made to monitor progress toward HIV diagnosis and antiretroviral treatment (ART) coverage targets in children, and the impact that ART and prevention of mother-to-child transmission (PMTCT) programs have had on pediatric HIV incidence and mortality.MethodsA multiparameter evidence synthesis approach was adopted to integrate South African pediatric HIV data sources. A previously developed model of HIV in South Africa was calibrated to household survey HIV prevalence data, routine antibody testing data, data on numbers and ages of children on ART, vital registration data and data on HIV diagnosis at death. The impact of ART and PMTCT was estimated by comparing validated model outputs against model predictions of the trends that would have been expected in the absence of ART and PMTCT.ResultsBy mid-2018, the model estimated that 75.2% (95% CI: 73.9%-76.8%) of HIV-positive children were diagnosed, substantially lower than the corresponding estimates in HIV-positive adults (91.0%). ART coverage in children in 2018 (51.2%, 95% CI: 49.4%-52.7%) was also lower than that in adults (62.0%). In 2017-2018, the numbers of new cases of mother-to-child transmission and pediatric AIDS deaths were reduced by 84% and 94%, respectively, relative to what would have been expected in the absence of interventions, but reductions in mortality were driven largely by PMTCT.ConclusionsAlthough levels of AIDS mortality in children have declined dramatically in South Africa, this has mostly been due to successful PMTCT programs, and progress toward the 90-90-90 targets appears relatively poor when compared with that in adults.
| S-EPMC7958302 | biostudies-literature
Project description:OBJECTIVE:The aim of this study was to assess the impact of obesity on pediatric acute recurrent pancreatitis or chronic pancreatitis (CP). METHODS:We determined body mass index (BMI) status at enrollment in INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) cohort using CDC criteria for pediatric-specific BMI percentiles. We used the Cochran-Armitage test to assess trends and the Jonckheere-Terpstra test to determine associations. RESULTS:Of 446 subjects (acute recurrent pancreatitis, n = 241; CP, n = 205), 22 were underweight, 258 normal weight, 75 overweight, and 91 were obese. The BMI groups were similar in sex, race, and age at presentation. Hypertriglyceridemia was more common in overweight or obese. Obese children were less likely to have CP and more likely to have acute inflammation on imaging. Compared with children with normal weight, obese or overweight children were older at first acute pancreatitis episode and diagnosed with CP at an older age. Obese or overweight children were less likely to undergo medical or endoscopic treatment, develop exocrine pancreatic insufficiency, and require total pancreatectomy with islet autotransplantation. Diabetes was similar among all groups. CONCLUSIONS:Obesity or overweight seems to delay the initial acute pancreatitis episode and diagnosis of CP compared with normal weight or underweight. The impact of obesity on pediatric CP progression and severity deserves further study.
| S-EPMC6095802 | biostudies-literature
Project description:ObjectivesThe aim of this study was to determine if comprehensive genetic testing was useful to identify genetic variants that discriminate chronic pancreatitis (CP) from acute recurrent pancreatitis (ARP) in a pediatric population.MethodsWe conducted a retrospective review of 50 patients enrolled in our institutional pancreatitis registry between April 2013 and January 2015. Genetic analysis of PRSS1, CFTR, SPINK1, and CTRC classified variants as mutations or variants of unknown clinical significance and the minor allele frequency of variants in our cohort was obtained.ResultsGenetic testing was obtained in 16/16 (100%) of CP and 29/34 (85%) of ARP patients. A total of 39 genetic variants were found in 27 (60%) of 45 subjects tested with 5 (11%) subjects having 2 different genes affected. Variant frequency was greatest in patients for CFTR (17/45, 38%) followed by SPINK1 (11/44, 25%), CTRC (2/27, 7%), and PRSS1 (2/44, 4%). CFTR variants were more likely in those with CP compared to ARP (63% and 24%, P = 0.01).ConclusionsThis study is the first to find a higher rate of CFTR mutations in CP versus ARP groups using comprehensive genetic testing in a pediatric population.
| S-EPMC5021552 | biostudies-literature
Project description:Pannexins are homologous to innexins, the invertebrate gap junction family. However, mammalian pannexin1 does not form canonical gap junctions, instead forming hexameric oligomers in single plasma membranes and intracellularly. Pannexin1 acts as an ATP release channel, whereas less is known about the function of Pannexin2. We purified cellular membranes isolated from MDCK cells stably expressing rat Pannexin1 or Pannexin2 and identified pannexin channels (pannexons) in single membranes by negative stain and immunogold labeling. Protein gel and Western blot analysis confirmed Pannexin1 (Panx1) or Pannexin2 (Panx2) as the channel-forming proteins. We expressed and purified Panx1 and Panx2 using a baculovirus Sf9 expression system and obtained doughnut-like structures similar to those seen previously in purified connexin hemichannels (connexons) and mammalian membranes. Purified pannexons were comparable in size and overall appearance to Connexin46 and Connexin50 connexons. Pannexons and connexons were further analyzed by single-particle averaging for oligomer and pore diameters. The oligomer diameter increased with increasing monomer molecular mass, and we found that the measured oligomeric pore diameter for Panxs was larger than for Connexin26. Panx1 and Panx2 formed active homomeric channels in Xenopus oocytes and in vitro vesicle assays. Cross-linking and native gels of purified homomeric full-length and a C-terminal Panx2 truncation mutant showed a banding pattern more consistent with an octamer. We purified Panx1/Panx2 heteromeric channels and found that they were unstable over time, possibly because Panx1 and Panx2 homomeric pannexons have different monomer sizes and oligomeric symmetry from each other.
| S-EPMC2915678 | biostudies-literature
Project description: Not available
| S-EPMC8478374 | biostudies-literature
Project description:IMPORTANCE:Pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) are poorly understood. OBJECTIVE:To characterize and identify risk factors associated with ARP and CP in childhood. DESIGN, SETTING, AND PARTICIPANTS:A multinational cross-sectional study of children with ARP or CP at the time of enrollment to the INSPPIRE (International Study Group of Pediatric Pancreatitis: In Search for a Cure) study at participant institutions of the INSPPIRE Consortium. From August 22, 2012, to February 8, 2015, 155 children with ARP and 146 with CP (aged ?19 years) were enrolled. Their demographic and clinical information was entered into the REDCap (Research Electronic Data Capture) database at the 15 centers. Differences were analyzed using 2-sample t test or Wilcoxon rank sum test for continuous variables and Pearson ?2 test or Fisher exact test for categorical variables. Disease burden variables (pain variables, hospital/emergency department visits, missed school days) were compared using Wilcoxon rank sum test. MAIN OUTCOMES AND MEASURES:Demographic characteristics, risk factors, abdominal pain, and disease burden. RESULTS:A total of 301 children were enrolled (mean [SD] age, 11.9 [4.5] years; 172 [57%] female); 155 had ARP and 146 had CP. The majority of children with CP (123 of 146 [84%]) reported prior recurrent episodes of acute pancreatitis. Sex distribution was similar between the groups (57% female in both). Hispanic children were less likely to have CP than ARP (17% vs 28%, respectively; odds ratio [OR]?=?0.51; 95% CI, 0.29-0.92; P?=?.02). At least 1 gene mutation in pancreatitis-related genes was found in 48% of patients with ARP vs 73% of patients with CP (P?<?.001). Children with PRSS1 or SPINK1 mutations were more likely to present with CP compared with ARP (PRSS1: OR?=?4.20; 95% CI, 2.14-8.22; P?<?.001; and SPINK1: OR?=?2.30; 95% CI, 1.03-5.13; P?=?.04). Obstructive risk factors did not differ between children with ARP or CP (33% in both the ARP and CP groups), but toxic/metabolic risk factors were more common in children with ARP (21% overall; 26% in the ARP group and 15% in the CP group; OR?=?0.55; 95% CI, 0.31-0.99; P?=?.046). Pancreatitis-related abdominal pain was a major symptom in 81% of children with ARP or CP within the last year. The disease burden was greater in the CP group compared with the ARP group (more emergency department visits, hospitalizations, and medical, endoscopic, and surgical interventions). CONCLUSIONS AND RELEVANCE:Genetic mutations are common in both ARP and CP. Ethnicity and mutations in PRSS1 or SPINK1 may influence the development of CP. The high disease burden in pediatric CP underscores the importance of identifying predisposing factors for progression of ARP to CP in children.
| S-EPMC5317277 | biostudies-literature
Project description:BackgroundThere is no published systematic review on the etiologies of chronic cough or the relationship between OSA and chronic cough in children aged ? 14 years. We thus undertook a systematic review based on key questions (KQs) using the Population, Intervention, Comparison, Outcome format. The KQs follow: Among children with chronic (> 4 weeks) cough (KQ 1) are the common etiologies different from those in adults? (KQ 2) Are the common etiologies age or setting dependent, or both? (KQ 3) Is OSA a cause of chronic cough in children?MethodsWe used the CHEST Expert Cough Panel's protocol and the American College of Chest Physicians (CHEST) methodological guidelines and Grading of Recommendations Assessment, Development, and Evaluation framework. Data from the systematic reviews in conjunction with patients' values and preferences and the clinical context were used to form recommendations. Delphi methodology was used to obtain consensus.ResultsCombining KQs 1 and 2, we found moderate-level evidence from 10 prospective studies that the etiologies of cough in children are different from those in adults and are setting dependent. Data from three studies found that common etiologies of cough in young children were different from those in older children. However, data relating sleep abnormalities to chronic cough in children were found only in case studies.ConclusionsThere is moderate-quality evidence that common etiologies of chronic cough in children are different from those in adults and are dependent on age and setting. As there are few data relating OSA and chronic cough in children, the panel suggested that these children should be managed in accordance with pediatric sleep guidelines.
| S-EPMC6026225 | biostudies-literature
Project description:We present here a genome-wide map of abnormalities found in diagnostic samples from 45 adults and adolescents with acute lymphoblastic leukemia (ALL). A 500K SNP array analysis uncovered frequent genetic abnormalities, with cryptic deletions constituting half of the detected changes, implying that microdeletions are a characteristic feature of this malignancy. Importantly, the pattern of deletions resembled that recently reported in pediatric ALL, suggesting that adult, adolescent, and childhood cases may be more similar on the genetic level than previously thought. Thus, 70% of the cases displayed deletion of one or more of the CDKN2A, PAX5, IKZF1, ETV6, RB1, and EBF1 genes. Furthermore, several genes not previously implicated in the pathogenesis of ALL were identified as possible recurrent targets of deletion. In total, the SNP array analysis identified 367 genetic abnormalities not corresponding to known copy number polymorphisms, with all but two cases (96%) displaying at least one cryptic change. The resolution level of this SNP array study is the highest used to date to investigate a malignant hematologic disorder. Our findings provide insights into the leukemogenic process and may be clinically important in adult and adolescent ALL. Most importantly, we report that microdeletions of key genes appear to be a common, characteristic feature of ALL that is shared among different clinical, morphological, and cytogenetic subgroups.
| S-EPMC2373322 | biostudies-literature
Project description:Hereditary chronic pancreatitis (HCP) is a very rare form of early onset chronic pancreatitis. With the exception of the young age at diagnosis and a slower progression, the clinical course, morphological features and laboratory findings of HCP do not differ from those of patients with alcoholic chronic pancreatitis. As well, diagnostic criteria and treatment of HCP resemble that of chronic pancreatitis of other causes. The clinical presentation is highly variable and includes chronic abdominal pain, impairment of endocrine and exocrine pancreatic function, nausea and vomiting, maldigestion, diabetes, pseudocysts, bile duct and duodenal obstruction, and rarely pancreatic cancer. Fortunately, most patients have a mild disease. Mutations in the PRSS1 gene, encoding cationic trypsinogen, play a causative role in chronic pancreatitis. It has been shown that the PRSS1 mutations increase autocatalytic conversion of trypsinogen to active trypsin, and thus probably cause premature, intrapancreatic trypsinogen activation disturbing the intrapancreatic balance of proteases and their inhibitors. Other genes, such as the anionic trypsinogen (PRSS2), the serine protease inhibitor, Kazal type 1 (SPINK1) and the cystic fibrosis transmembrane conductance regulator (CFTR) have been found to be associated with chronic pancreatitis (idiopathic and hereditary) as well. Genetic testing should only be performed in carefully selected patients by direct DNA sequencing and antenatal diagnosis should not be encouraged. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications, such as pseudocysts, bile duct or duodenal obstruction. The disease course and prognosis of patients with HCP is unpredictable. Pancreatic cancer risk is elevated. Therefore, HCP patients should strongly avoid environmental risk factors for pancreatic cancer.
| S-EPMC1774562 | biostudies-literature
Project description:Background. The clinical pattern and genetic background of juvenile idiopathic chronic pancreatitis (ICP) are yet unclear. Methods. A retrospective study of 73 Chinese juvenile ICP patients was performed, and genetic tests were carried out to detect relevant mutations using direct sequencing technique and high-resolution melting technique. Subjects without pancreatitis served as controls. Results. The SPINK1 c.194+2T>C variant was present in 56.16% and 42.00% of juvenile and adult ICP patients, respectively (p = 0.020), but was not present in any of the control subjects. Thirty-four (46.58%) of the 73 juvenile ICP patients were male, and a significantly higher ratio of male patients in the adult group was identified (46.58% versus 64.00%, p = 0.022). Although most of the juvenile patients presented with abdominal pain (70/73, 95.89%), the patterns of pain attack are significantly different in patients with or without SPINK1 c.194+2T>C mutation. Patients carrying the mutation are more likely to present with recurrent acute pancreatitis (70.70%). Conclusions. The main symptom of pediatric ICP was abdominal pain. SPINK1 c.194+2T>C mutation had a higher occurrence in juvenile ICP patients than in adult group and typically presented with recurrent acute pancreatitis. There may be unidentified factors that lead to a greater incidence rate of ICP in adult male population.
| S-EPMC5350339 | biostudies-literature