Assessing the accuracy and reliability of satellite-derived precipitation products in the Kosi River basin (India).

The present research endeavors to examine the effectiveness of four gridded precipitation datasets, namely Integrated Multi-satellite Retrievals for GPM (IMERG), Tropical Precipitation Measuring Mission (TRMM), Modern-Era Retrospective Analysis for Research and Applications Version 2 (MERRA-2), and Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks (PERSIANN), with the observed rainfall data of eight rain gauge stations of India Meteorological Department (IMD) from 2001 to 2019 in Kosi River basin, India. Various statistical metrics, contingency tests, trend analysis, and rainfall anomaly index were utilized at daily, monthly, seasonal, and annual time scales. The categorical metrics namely probability of detection (POD) and false alarm ratio (FAR) indicate that MERRA-2 and IMERG datasets have the highest level of concurrence with the observed daily data. Statistical analysis of gridded datasets with observed dataset of IMD showed that the performance of the IMERG dataset is better than MERRA-2, PERSIANN, and TRMM datasets with "very good" coefficient of determination (R2) and Nash-Sutcliffe Efficiency values for monthly data. Trend analysis of gridded seasonal data of IMERG showed similar trends of observed seasonal data whereas other dataset differs. IMERG also performed well in identifying wet and dry years based on annual data. Discrepancies of the satellite sensor in capturing the precipitation have also been discussed. Thus, the IMERG dataset can be effectively used for hydro-meteorological and climatological investigations in cases of lack of observed datasets.

Effect of land use land cover changes on hydrological response of Punpun River basin.

The present study assessed the hydrological response of land use land cover (LULC) change on the Punpun River basin. High-resolution gridded rainfall and temperature data from the years 1995 to 2020 have been used in the Soil and Water Assessment Tool (SWAT) in the Geographic Information System (GIS) to analyze the hydrological response of the Punpun River basin and water balance components. Hydrological Response Units (HRUs) have been created for the basin. Each HRU is based on a distinct combination of soil, slope, and land use. Five SWAT models have been prepared based on the LULC of every 5-year interval to simulate the basin's hydrological response. The period selected for calibration is 1995-2015 and for validation is 2016-2020 for the modeling of daily streamflow data. The observed and simulated streamflow was checked for performance indices of coefficient of determination (R2), Nash-Sutcliffe Efficiency (NSE), and percent bias (PBIAS) on daily time steps. The results were found to be good with R2 = 0.72, NSE = 0.68, and PBIAS = 23.2 for calibration and R2 = 0.93, NSE = 0.77, and PBIAS = 19.8 for validation. The study reveals that 7.01% of evapotranspiration (ET) was increased from 1995 to 2020 with increase in agricultural area of 21.86%. It was also found that built-up area, surface runoff, and water yield have been increased by 9.14, 14.43, and 17.40%, respectively. Further, the groundwater contribution of the basin was decreased.

A cross-sectional study of nausea in functional abdominal pain: relation to mucosal mast cells and psychological functioning.

BACKGROUND: Nausea is a common symptom in youth with chronic abdominal pain. The aims of the current study were to assess: 1) the frequency of nausea in patients with functional dyspepsia (FD) and irritable bowel syndrome (IBS), respectively, as defined by Rome IV criteria; and, 2) relationships between nausea and mucosal inflammation as defined by antral and duodenal eosinophil and mast cell densities. A secondary aim was to assess relationships between nausea and other gastrointestinal symptoms, non-gastrointestinal somatic symptoms, and psychological dysfunction. METHODS: Records from patients with pain associated functional gastrointestinal disorders were retrospectively reviewed for gastrointestinal and somatic symptoms and anxiety, depression, and somatizations scores as assessed by the Behavior Assessment System for Children (BASC-2). In addition, previous gastric and mucosal biopsies were assessed for mast cell and eosinophil densities, respectively. RESULTS: 250 patients, ages 8 to 17 years, were assessed. Nausea was reported by 78% and was equally prevalent in those with FD alone, those with IBS alone, and those with both FD and IBS. Nausea was associated with increased mean (21.4 vs. 17.5) and peak (26.2 vs. 22.9) duodenal mast cell densities as compared those without nausea. Nausea was also associated with a wide variety of individual gastrointestinal symptoms, as well as headaches, fatigue, and dizziness. Lastly, nausea was associated with elevated self-report scores for anxiety (55.2 vs. 50.0), depression (50.2 vs. 46.1), and somatization (70.3 vs. 61.8). CONCLUSIONS: Nausea is common in children and adolescents with pain-associated FGIDs as defined by Rome IV and is not unique to either FD or IBS. Nausea is associated with increased mucosal mast cell density, non-gastrointestinal somatic symptoms, and psychologic dysfunction.

Mucosal Th17 Cells Are Increased in Pediatric Functional Dyspepsia Associated with Chronic Gastritis.

BACKGROUND: Chronic gastritis is a common histologic finding in children with functional dyspepsia (FD). While Th17 cells have been implicated in other forms of gastritis, they have not been evaluated in chronic gastritis. AIMS: The aim of the current study was to assess Th17 cells in children with FD with and without chronic gastritis. METHODS: Densities were determined for Th17 cells, eosinophils, and mast cells, respectively, in both the gastric antrum and the duodenum. Densities were compared between five groups: FD with chronic gastritis (N = 20), FD without chronic gastritis (N = 20), Helicobacter pylori-associated gastritis (N = 10), Crohn's gastritis (N = 10), and normal controls (N = 10). Th17 densities were also compared between patients with and without early satiety. RESULTS: FD with chronic gastritis was associated with higher Th17 cell density as compared to normal controls and comparable to both H. pylori-associated gastritis and Crohn's gastritis. Eosinophil and mast cell densities were higher in FD patients with chronic gastritis as compared to either FD without gastritis or normal controls. Th17 density was higher in patients reporting early satiety but not in those with epigastric pain. CONCLUSIONS: FD with chronic gastritis is associated with higher Th17 cell, eosinophil, and mast cell density as compared to FD without chronic gastritis or normal controls. Chronic gastritis demonstrated Th17 cell density similar to that seen in other conditions where Th17 cells are believed to play a pathogenic role. Th17 cells may represent another therapeutic target in these patients.

The relationship of eosinophilia with outcomes of Hirschsprung disease in children.

PURPOSE: It has been postulated that children with Hirschsprung disease (HD) and mucosal eosinophilia have been thought to have poorer outcome, but supporting evidence is lacking. The objective of our study was to review the outcomes of children with HD and mucosal eosinophilia. METHODS: A single center, retrospective review was conducted on all patients diagnosed with HD between 1999 and 2016. Pathology specimens were evaluated for mucosal eosinophilia. Demographics, complications, and outcomes were analyzed. RESULTS: A total of 100 patients were diagnosed with HD and 27 had mucosal eosinophilia. Median age at the time of surgery was 12 days (8, 30) and 82 were males. Comparing patients with HD with and without mucosal eosinophilia, there was no statistically significant difference in time to bowel function (2 days vs. 2 days; p = 0.85), time to start feeds (3 days vs. 3 days; p = 0.78) and time to goal feeds (5 days vs. 5 days; p = 0.47). There was no statistically significant difference in feeding issues (13% vs. 9%; p = 1.0) and stooling issues (60% vs. 50%; p = 0.38). There was no statistically significant difference in postoperative complications and readmissions rates (63% vs. 56%; p = 0.53). CONCLUSION: Hirschsprung-associated mucosal eosinophilia may not increase postoperative complications, and may not change feeding and bowel management. Further prospective studies are in process to evaluate long term follow-up outcomes for this patient population.

Immunohistochemical Staining of Pediatric Solitary Angiokeratomas.

The precise etiology and subtype of vessels constituting angiokeratomas is poorly understood. We sought to characterize the vessels by studying prospero-related homeobox gene-1 and D2-40 expression in 22 pediatric solitary angiokeratomas. Routine histologic examination demonstrated a mix of lymph-containing vessels and erythrocyte-filled small vessels. Our results suggest that angiokeratomas may in part be comprised of vessels with lymphatic differentiation.

Decreased Pregnane X Receptor Expression in Children with Active Crohn's Disease.

Expression of the pregnane X receptor (PXR) has been reported to be decreased in animal models of inflammatory bowel disease (IBD). To investigate the differential expression of PXR in children with Crohn's disease, a type of IBD, RNA was extracted from archived intestinal biopsies from 18 children with Crohn's disease (CD) and 12 age- and sex-matched controls (aged 7-17yrs). The aim of this investigation was to compare the relative mRNA expression of PXR, cytochrome p450 3A4 (CYP3A4), and villin 1 (VIL1) (a marker of epithelial cell integrity) in the inflamed terminal ileum (TI) versus noninflamed duodenum of children with CD. Relative expression was determined via reverse transcription real-time quantitative polymerase chain reaction, data normalized to glyceraldehyde 3-phosphate dehydrogenase, and differences in gene expression explored via paired t tests. PXR expression was decreased in the inflamed TI versus noninflamed duodenum (TI = 1.88 ± 0.89 versus duodenum = 2.5 ± 0.67; P < 0.001) in CD, but not controls (TI = 2.11 ± 0.41 versus duodenum = 2.26 ± 0.61; P = 0.52). CYP3A4 expression was decreased in CD (TI = -0.89 ± 3.11 versus duodenum = 1.90 ± 2.29; P < 0.05), but not controls (TI = 2.46 ± 0.51 versus duodenum = 2.60 ± 0.60; P = 0.61), as was VIL1 (CD TI = 3.80 ± 0.94 versus duodenum = 4.61 ± 0.52; P < 0.001; controls TI = 4.30 ± 0.35 versus duodenum = 4.47 ± 0.40; P = 0.29). PXR expression correlated with VIL1 (r = 0.78, P = 0.01) and CYP3A4 (r = 0.52, P = 0.01) expression. In conclusion, PXR, CYP3A4, and VIL1 expression was decreased only in the actively inflamed small intestinal tissue in children with CD. Our findings suggest that inflammation has the potential to influence expression of genes, and potentially intestinal proteins, important to drug disposition and response. The observed differential patterns of gene expression support further investigation of the role of PXR in the pathogenesis and/or treatment of pediatric Crohn's disease.

Investigation of potential early Histologic markers of pediatric inflammatory bowel disease.

BACKGROUND: Early manifestations of pediatric inflammatory bowel disease (IBD) can be relatively nonspecific. Initial mucosal biopsies may not be conclusive, delaying the diagnosis until subsequent biopsies demonstrate typical histologic features of IBD. We hypothesized that certain inflammatory cell types may be utilized as early histologic indicators of IBD in children. METHODS: A retrospective analysis compared histologic findings from initially inconclusive or negative endoscopic studies in 22 patients who were subsequently diagnosed with IBD (after diagnostic endoscopy) to those of 20 comparison patients with functional abdominal pain matched for age, gender, and study type. A pediatric pathologist, blinded to study group, reviewed biopsies for histologic abnormalities. Eosinophil densities were obtained from the stomach, duodenum, and rectosigmoid areas. Immunohistochemistry (IHC) staining for tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-9 (MMP-9) was performed on the stomach and rectosigmoid areas. RESULTS: Gastritis and colonic crypt distortion were present in the IBD group at a greater rate (61 % vs. 22 %, p = 0.020; 34 % vs. 4 %, p = 0.008, respectively). Peak and mean eosinophil densities in the rectosigmoid area were greater in the IBD group (17.0/hpf vs. 5.0/hpf, p = 0.0063; 12.3/hpf vs. 4.2/hpf, p = 0.0106, respectively). TNF-α and MMP-9 staining did not reveal any significant differences. CONCLUSIONS: Our data suggests that significantly greater inflammation in the stomach, crypt distortion in the colon, and eosinophilia in the rectosigmoid distinguished the IBD group from the comparison group at the time of the initial endoscopic evaluation.

Molecular diagnosis of infantile onset inflammatory bowel disease by exome sequencing.

Pediatric-onset inflammatory bowel disease (IBD) is known to be associated with severe disease, poor response to therapy, and increased morbidity and mortality. We conducted exome sequencing of two brothers from a non-consanguineous relationship who presented before the age of one with severe infantile-onset IBD, failure to thrive, skin rash, and perirectal abscesses refractory to medical management. We examined the variants discovered in all known IBD-associated and primary immunodeficiency genes in both siblings. The siblings were identified to harbor compound heterozygous mutations in IL10RA (c.784C>T, p.Arg262Cys; c.349C>T, p.Arg117Cys). Upon molecular diagnosis, the proband underwent successful hematopoietic stem cell transplantation and demonstrated marked clinical improvement of all IBD-associated clinical symptoms. Exome sequencing can be an effective tool to aid in the molecular diagnosis of pediatric-onset IBD. We provide additional evidence of the safety and benefit of HSCT for patients with IBD due to mutations in the IL10RA gene.

Mucosal prolapse syndrome mimicking Peutz-Jeghers syndrome in a pediatric patient.

Mucosal prolapse syndrome (MPS) is a rare group of benign conditions characterized by a set of unifying histologic findings thought to be the result of repeated mucosal shearing and submucosal vascular congestion caused by straining. This set of conditions is often misdiagnosed as other polyposis syndromes, inflammatory bowel disease, or malignancy due to its clinical presentation, appearance, and rarity. We report a case of a 15-year-old male who presented with painless rectal bleeding. He was found to have four rectal polyps thought to be due to Peutz-Jeghers syndrome. A repeat colonoscopy with biopsies a year later revealed a diagnosis of MPS. Our case highlights the morphologic similarity between hamartomatous polyp and mucosal prolapse histology. Since MPS is a rare diagnosis even among the adult population, it has not been well described in pediatrics. This syndrome should be on the differential diagnosis for pediatric rectal polyps to prevent unnecessary invasive testing and a delay in treatment.

Impact of Duodenal Pathology on Oral Drug Bioavailability and Disease Outcomes in Pediatric Crohn's Disease.

BACKGROUND: Crohn's disease with upper gastrointestinal tract involvement occurs more often in children than adults and has the potential to interfere with oral drug absorption. We aimed to compare disease outcomes in children receiving oral azathioprine for the treatment of Crohn's disease with (DP) and without (NDP) duodenal pathology at diagnosis. METHODS: Duodenal villous length, body mass index (BMI), and laboratory studies were compared in DP vs. NDP during the first year post-diagnosis, using parametric/nonparametric tests and regression analysis (SAS v9.4); the data are reported as the median (interquartile range) or the mean ± standard deviation. Thiopurine metabolite concentration (pmol/8 × 108 erythrocytes) 230-400 was considered therapeutic for 6-thioguanine nucleotides (6-TGN), and >5700 was considered hepatotoxic for 6-methylmercaptopurine (6-MMPN). RESULTS: Twenty-six of the fifty-eight children enrolled (29 DP, 29 NDP) started azathioprine for standard medical care, including nine DP and ten NDP who had normal thiopurine methyltransferase activity. Duodenal villous length was significantly shorter in DP vs. NDP (342 ± 153 vs. 460 ± 85 µm; p < 0.001) at diagnosis; age, sex, hemoglobin, and BMI were comparable between groups. A trend toward lower 6-TGN was observed in the DP vs. NDP subset receiving azathioprine (164 (117, 271) vs. 272 (187, 331); p = 0.15). Compared to NDP, DP received significantly higher azathioprine doses (2.5 (2.3, 2.6) vs. 2.2 (2.0, 2.2) mg/kg/day; p = 0.01) and had an increased relative risk of sub-therapeutic 6-TGN. At 9 months post-diagnosis, children with DP had significantly lower hemoglobin (12.5 (11.7, 12.6) vs. 13.1 (12.7, 13.3) g/dL; p = 0.01) and BMI z-scores (-0.29 (-0.93, -0.11) vs. 0.88 (0.53, 0.99); p = 0.02) than children with NDP. CONCLUSION: For children with Crohn's disease, duodenal pathology, marked by villous blunting, increased the risk of sub-therapeutic 6-TGN levels, despite higher azathioprine dosing during the first year post-diagnosis. Lower hemoglobin and BMI z-scores at 9 months post-diagnosis suggest the impaired absorption/bioavailability of nutrients, as well as oral drugs, in children with duodenal disease.

Free Flap Reconstruction in a Tongue Cancer Patient with Nephrotic Syndrome: A Case Report.

Free flap has become crucial for reconstruction in head and neck oncology post resection since the time of its advent. It has shown a high success rate and provides a better quality of life over loco regional flaps. Literature has shown the success of free flaps does get influenced by preexisting medical conditions of the patient. Nephrotic syndrome being a hypercoagulable state doesn't find much mention in literature and its effect on free flaps has been less studied. Hence, using a free flap in such condition creates a decision making dilemma. Here we present a case report to show the feasibility of such flaps in nephrotic syndrome patients under structured environment successfully.

Urethral pyogenic granuloma in a pediatric patient.

Pyogenic granuloma, also known as lobular capillary hemangioma, is a benign vascular tumor rarely found in the genitourinary tract. Here, we present a case of a 6-year-old boy presenting with gross hematuria who was found to have a mass at the bladder base on ultrasound. Endoscopic resection was performed, revealing the base of the mass originating from the prostatic urethra. Pathology found pyogenic granuloma. This entity has not previously been reported to arise from the pediatric urethra and should be considered on the differential for children presenting with gross hematuria and those found to have bladder or urethral masses.

Do Histologic Features of the Proximal Margin of Resected Specimens Predict Clinical Outcomes in Hirschsprung Disease?

Objective Patients with Hirschsprung disease (HSCR) can experience obstructive symptoms despite adequate resection. We sought to determine if submucosal nerve thickness or length of ganglionated bowel in the resected specimen correlated with functional outcomes. Methods A retrospective study of patients who underwent surgery between 2015-2019 was performed. The resected specimen was scanned to measure areas of the thickest submucosal nerves and the length of the ganglionated segment. Functional outcomes were collected via chart review. Results Thirty patients were included. The median age at pull-through was 4.5 months (interquartile range {IQR} 0.5 - 6.7 months); 70% were male, and 57% had a Swenson pull-through. The median size of the thickest nerves was 28 micrometers (IQR 24, 32). Three specimens had a nerve thickness of >40 micrometers. The median length of the resected ganglionated segment was 4.4 cm (IQR 2.2, 7.2). Out of the total, 53% of patients experienced post-operative enterocolitis; 13% required further surgery. At a median of 25.3 months (IQR 17.6, 42.2 months) from pull-through, 33% did not require any bowel regimen therapy. Utilizing logistic regression, neither submucosal nerve thickness nor length of the resected ganglionic segment correlated with outcomes. Conclusion While continued bowel management therapy was common, no correlation was found between histologic findings and functional outcomes.

Cytoplasmic P53 Immunostaining With N-Terminus P53 Antibody And Absence Of Staining With C-Terminus P53 Antibody: A Report Of Two Pediatric Sarcomas With Distal Truncating TP53 Mutations Affecting Nuclear Localization Domain.

P53 immunohistochemical staining with antibodies targeted to epitopes at or near the N-terminus are commonly used in diagnostic pathology practice as a surrogate for TP53 mutations. The abnormal staining patterns indicating TP53 mutations include nuclear overexpression, null, and the recently described cytoplasmic staining. The latter staining pattern occurs with the less common TP53 mutations affecting its nuclear localization and/or tetramerization domains that are located toward the C-terminus. Here we describe the first two cases of pediatric sarcomas with cytoplasmic staining with P53 antibody against N-terminus epitope and the absence of staining with P53 antibody against C-terminus epitope. We propose that a more precise description of P53 immunohistochemical staining patterns should include the nature of the antibody used.

Characterization of the Mucosally-Adherent Duodenal Microbiome in Children with and without Crohn's Disease.

Manipulation of the microbiome is a rational treatment strategy for inflammatory bowel disease (IBD). Compared to the colon and terminal ileum (TI), understanding of the microbial composition in the duodenum is sparse. This gap in knowledge is especially significant for children with Crohn's disease (CD) because the prevalence of duodenal CD is higher in children than in adults. Our aim was to characterize the bacterial composition of the mucosally-adherent duodenal microbiome in children with and without CD as a first step toward development of targeted IBD treatment strategies at this disease location. Fresh-frozen mucosal biopsies were obtained from the duodenum and TI of children with treatment-naïve CD and age- and sex-matched controls. Extracted DNA was analyzed for sequence variation in the 16S ribosomal RNA bacterial gene region V4 (Novogene; Beijing, China). Bacterial relative abundance, alpha and beta composition, and diversity, were compared across duodenal and TI samples from the controls and CD groups with and without chronic active inflammation (118 samples from 73 children total; approx. 50% CD), using UniFrac dissimilarity coefficients (α < 0.05), Linear Discriminant Analysis Effect Size (LEfSe) analysis (LDA score ≥ 2), and Unweighted Pair Group Method with Arithmetic Mean (UPGMA) analysis. The relationships between bacterial abundance, sex, age, concomitant medication use, and villous length were assessed. The microbial composition in the duodenum was significantly different from the TI in the control population(R-value = 0.558, p = 0.001) and in children with active CD (R-value = 0.301, p = 0.001). Significant differences in bacterial abundance were noted between the control and CD duodena (LDA > 4). The duodenum of children without CD was characterized by increased abundance in Pseudomonodales, whereas the actively inflamed duodenum in CD was characterized by increased abundance of Bacteroidales, specifically the family Prevotellaceae. This trend is opposite of previously published observations of microbial composition in the TI, where active inflammation was associated with a relative decrease in the abundance of Bacteroidetes and an increase in Proteobacteria, including Pseudomonadales. No statistically significant correlations were noted between abundance and age, sex, concomitant medication use or villous length, except for Bacteroidetes, which significantly decreased in abundance in the TI with age (p = 0.048). The pediatric duodenal microbiome is distinct from the TI and characterized by an increased abundance of Pseudomonodales and Spirochetes in healthy children, and an increased abundance of Bacteroidales in active CD patients.

Colonic mucosal eosinophilia in children without inflammatory bowel disease.

Children undergoing colonoscopy and mucosal biopsies may show increased colonic mucosal eosinophils, which may or may not be associated with inflammatory bowel disease. There is not much clinical data on American children who have isolated increased colonic mucosal eosinophils. We sought to study the clinical correlates of children without inflammatory bowel disease who show increased mucosal eosinophils to understand their clinical presentation, etiological associations, and outcome. A retrospective analysis of children seen at a tertiary-level Children's hospital was performed by reviewing their medical charts and extracting pertinent data. There were 110 children in the study who had increased colonic mucosal eosinophils. Most children presented with abdominal pain, but several of them also had constipation, blood in stools, and diarrhea. Food allergies, irritable bowel syndrome, asthma, and lactase deficiency were the top four conditions present in these patients. Pathology of the colonic distribution revealed involvement of more than two colonic regions in 86% of the subjects, and only two subjects showing epithelial or crypt involvement by eosinophils. All subjects had a good outcome. Children with colonic mucosal eosinophilia (CME) who do not have an inflammatory bowel disease most frequently present with abdominal pain and primarily an increase of lamina propria eosinophils in two or more colonic regions. Based on the etiological associations we noted in the study, a work-up of children with CME may encompass detailed history for functional gastrointestinal disorders and lactose intolerance, testing for food and environmental allergies, stool examination for parasites, and peripheral blood counts. Almost all children had resolution of symptoms in the studied period suggesting that CME in children has a good clinical outcome.

Effect of Crohn's Disease on Villous Length and CYP3A4 Expression in the Pediatric Small Intestine.

Changes in absorptive capacity and first-pass metabolism in the small intestine affect oral drug bioavailability. Characterization of such changes as a consequence of inflammation is important for developing physiologically-based pharmacokinetic (PBPK) models for inflammatory bowel disease. We sought to elucidate the impact of small intestinal Crohn's disease (CD) on villous length and CYP3A4 expression in children. Freshly frozen duodenal and terminal ileum (TI) biopsies from 107 children (1-19 years) with and without CD were evaluated for active inflammation. Villous length and CYP3A4 mRNA/protein expression were compared among regions of active and inactive inflammation in CD and controls. A twofold reduction in villous length was observed in inflamed duodena and ilia of children with CD, but in the absence of regional inflammation, villi in CD were comparable in length to controls. Expression of CYP3A4 mRNA correlated significantly with villous length in the TI (P = 0.0003), with a trend observed in the duodenum that did not reach statistical significance. In the presence of active inflammation, a significant decrease in CYP3A protein expression was confirmed in the duodenum, where protein expression also correlated significantly with villous length across diagnoses (P < 0.0001). Our findings suggest that previous observations of decreased CYP3A4 expression and function in inflamed intestine may not be due solely to downregulation by inflammatory cytokines, but also to villous blunting and subsequent loss of surface area for protein expression. This information is relevant for PBPK model development and could aid with dose adjustment decisions for oral CYP3A4 substrates administered during CD flare (e.g., budesonide).

Symptoms and subtypes in pediatric functional dyspepsia: relation to mucosal inflammation and psychological functioning.

OBJECTIVES: The aim of the present study was to explore relations between antral or duodenal inflammatory cells and aspects of psychological functioning with clinical symptom presentation in children with functional dyspepsia (FD), as well as to determine whether histologic inflammation and/or psychopathology are differentially associated with FD subtypes as defined by the Rome II and Rome III criteria. PATIENTS AND METHODS: One hundred pediatric patients with dyspepsia completed a standardized history and physical examination at initial evaluation. Patients and parents also completed a measure of psychological functioning. Subsequently, 63 of these patients underwent upper endoscopy with biopsy (4 patients excluded from analysis because of mucosal disease). Inflammatory cells in the mucosa of stomach and duodenum were enumerated. Associations between specific symptoms and FD subtypes with inflammatory cell densities and anxiety, depression, and somatization scores were examined. RESULTS: Rome III subtypes were more robustly related to differences in mast cell densities and scores on psychologic subscales than was true for Rome II subtypes. At the individual symptom level, having pain wake the patient from sleep was associated with higher duodenal mast cell density. Bloating was associated with lower levels of general antral inflammation, as well as higher self-reported levels of anxiety and somatization. Early satiety and bothersome postprandial fullness also were associated with higher levels of self-reported anxiety and depression. CONCLUSIONS: The present study provides preliminary evidence for a relation between clinical presentation, specific types of inflammatory cell infiltrates, and aspects of psychological functioning in children with FD. Rome III subtyping, adopted for adult dyspepsia, may be relevant to the pediatric population.