Utilization of Antitumor Necrosis Factor Biologics in Very Early Onset Inflammatory Bowel Disease: A Multicenter Retrospective Cohort Study From North America.

BACKGROUND: Research on the utilization and effectiveness of antitumor necrosis factor (TNF) biologics in children with very early onset inflammatory bowel disease (VEOIBD) is urgently needed. Here we describe anti-TNF use and durability in a multicenter cohort. METHODS: We performed a retrospective cohort study of patients diagnosed with VEOIBD (<6 years) between 2008 and 2013 at 25 North American centers. We performed chart abstraction at diagnosis and 1, 3, and 5 years after diagnosis. We examined the rate of initiation and durability of infliximab and adalimumab and evaluated associations between treatment durability and the following covariates with multivariate Cox proportional hazard regression: age at diagnosis, sex, disease duration, disease classification, and presence of combined immunomodulatory treatment versus monotherapy. RESULTS: Of 294 children with VEOIBD, 120 initiated treatment with anti-TNF therapy and 101 had follow-up data recorded [50% Crohn disease (CD), 31% ulcerative colitis (UC), and 19% IBD unclassified (IBD-U)]. The cumulative probability of anti-TNF treatment was 15% at 1 year, 30% at 3 years, and 45% at 5 years from diagnosis; 56 (55%) were treated between 0 and 6 years old. Anti-TNF durability was 90% at 1 year, 75% at 3 years, and 55% at 5 years. The most common reason for discontinuation of anti-TNF were loss of response in 24 (57%) children. Children with UC/IBD-U had lower durability than those with CD (hazard ratio [HR] 0.17; 95% confidence interval [CI], 0.06-0.51; P = 0.001). CONCLUSIONS: Utilization and durability of anti-TNF in VEOIBD is relatively high and comparable with older children. Having Crohn disease (compared with UC/IBD-U) is associated with greater durability.

Biologics Delay Progression of Crohn's Disease, but Not Early Surgery, in Children.

BACKGROUND & AIMS: Up to 30% of patients with Crohn's disease (CD) require surgery within the first 5 years from diagnosis. We investigated the recent risk of bowel surgery in an inception cohort of pediatric patients with CD and whether early use of biologics (tumor necrosis factor antagonists) alters later disease course. METHODS: We collected data from the Pediatric Inflammatory Bowel Disease Collaborative Research Group registry on 1442 children (age, ≤16 y) diagnosed with CD from January 2002 through December 2014. Data were collected at diagnosis, 30 days following diagnosis, and then quarterly and during hospitalizations for up to 12 years. Our primary aim was to determine the 10-year risk for surgery in children with CD. Our secondary aim was to determine whether early use of biologics (<3 mo of diagnosis) affected risk of disease progression. RESULTS: The 10-year risk of first bowel surgery was 26%. The 5-year risk of bowel surgery did not change from 2002 through 2014, and remained between 13% and 14%. Most surgeries occurred within 3 years from diagnosis. The only predictor of surgery was disease behavior at diagnosis. CD with inflammatory behavior had the lowest risk of surgery compared to stricturing disease, penetrating disease, or both. We associated slowing of disease progression to stricturing or penetrating disease (but not surgery) with early use of biologics, but this effect only became evident after 5 years of disease. Our results indicate that biologics slow disease progression over time (hazard ratio, 0.85; 95% CI, 0.76-0.95). CONCLUSIONS: In an analysis of data from a registry of pediatric patients with CD, we found that among those with significant and progressing disease at or shortly after presentation, early surgery is difficult to prevent, even with early use of biologics. Early use of biologics (<3 mo of diagnosis) can delay later disease progression to stricturing and/or penetrating disease, but this affect could become evident only years after initial management decisions are made.

Impact of surgical pulmonary valve replacement on ventricular strain and synchrony in patients with repaired tetralogy of Fallot: a cardiovascular magnetic resonance feature tracking study.

BACKGROUND: In patients with repaired tetralogy of Fallot (TOF), a better understanding of the impact of surgical pulmonary valve replacement (PVR) on ventricular mechanics may lead to improved indications and outcomes. Therefore, we used cardiovascular magnetic resonance (CMR) feature tracking analysis to quantify ventricular strain and synchrony in repaired TOF patients before and after PVR. METHODS: Thirty-six repaired TOF patients (median age 22.4 years) prospectively underwent CMR a mean of 4.5 ± 3.8 months before PVR surgery and 7.3 ± 2.1 months after PVR surgery. Feature tracking analysis on cine steady-state free precession images was used to measure right ventricular (RV) and left ventricular (LV) circumferential strain from short-axis views at basal, mid-ventricular, and apical levels; and longitudinal strain from 4-chamber views. Intraventricular synchrony was quantified using the maximum difference in time-to-peak strain, the standard deviation of the time-to-peak, and cross correlation delay (CCD) metrics; interventricular synchrony was assessed using the CCD metric. RESULTS: Following PVR, RV end-diastolic volume, end-systolic volume, and ejection fraction declined, and LV end-diastolic volume and end-systolic volume both increased with no significant change in the LV ejection fraction. LV global basal and apical circumferential strains, and basal synchrony improved. RV global circumferential and longitudinal strains were unchanged, and there was a varied impact on synchrony across the locations. Interventricular synchrony worsened at the midventricular level but was unchanged at the base and apex, and on 4-chamber views. CONCLUSIONS: Surgical PVR in repaired TOF patients led to improved LV global strain and no change in RV global strain. LV and RV synchrony parameters improved or were unchanged, and interventricular synchrony worsened at the midventricular level.

Management of chronic intractable constipation in children.

BACKGROUND: Chronic intractable constipation (CIC) is a debilitating disease that is challenging to manage. Treatment options in children include medications, enemas, and surgical management in selected cases. METHOD: We reviewed medical records of pediatric patients diagnosed as having CIC at Tufts Medical Center from 2005 to 2012. Demographic variables, diagnostic procedures, and medical and surgical outcomes were collected. Clinical outcome was defined using the Rome III criteria. RESULTS: A total of 14 patients were included in the study (10 boys). The age range was 10 to 21 years. All of the patients had the diagnosis of CIC. Eleven patients had cecostomy placement. During the follow-up period, 10 patients underwent total abdominal colectomy with ileorectal anastomosis, 1 had total colectomy with ileostomy, and 1 had partial colectomy with colorectal anastomosis. Successful clinical outcome was reported in 7 patients with 3 patients reporting persistent fecal incontinence. Colonic motility studies were performed on 12 patients (colonic neuropathy in 11 patients and normal study in 1 patient). Defecography was consistent with isolated pelvic floor dysfunction in 1 patient, abnormal motility and anatomy in 1 patient, pelvic floor dysfunction and abnormal motility in 2 patients, and found abnormal motility only in 5. Defecography study was normal in 5 patients. All of the patients with abnormal colonic manometry underwent a surgical procedure. CONCLUSIONS: Anorectal manometry, colonic manometry, and defecography help in understanding the pathophysiology of defecation disorders in children. The majority of patients with abnormal colonic manometry underwent TAC-IRA. There was no statistical correlation between individual investigations (anorectal manometry, colonic manometry, and defecography) with surgical intervention (P > 0.35). TAC-IRA may be safe and useful intervention in a subset of patients when other treatment options have failed.

Thrombotic events in critically ill children with myocarditis.

BACKGROUND: Children with myocarditis have multiple risk factors for thrombotic events, yet the role of antithrombotic therapy is unclear in this population. We hypothesised that thrombotic events in critically ill children with myocarditis are common and that children with myocarditis are at higher risk for thrombotic events than children with non-inflammatory dilated cardiomyopathy. METHODS: This is a retrospective chart review of all children presenting to a single centre cardiac intensive care unit with myocarditis from 1995 to 2008. A comparison group of children with dilated cardiomyopathy was also examined. Antithrombotic regimens were recorded. The primary outcome of thrombotic events included intracardiac clots and any thromboembolic events. RESULTS: Out of 45 cases with myocarditis, 40% were biopsy-proven, 24% viral polymerase chain reaction-supported, and 36% diagnosed based on high clinical suspicion. There were two (4.4%) thrombotic events in the myocarditis group and three (6.7%) in the dilated cardiomyopathy group (p = 1.0). Neither the use of any antiplatelet or anticoagulation therapy, use of intravenous immune globulin, presence of any arrhythmia, nor need for mechanical circulatory support were predictive of thrombotic events in the myocarditis, dilated cardiomyopathy, or combined groups. CONCLUSIONS: Thrombotic events in critically ill children with myocarditis and dilated cardiomyopathy occurred in 6% of the combined cohort. There was no difference in thrombotic events between inflammatory and non-inflammatory cardiomyopathy groups, suggesting that the decision to use antithrombotic prophylaxis should be based on factors other than the underlying aetiology of a child's acute decompensated heart failure.

Radioactivity determination in depth distribution of stone samples of Kalaburagi District, Karnataka, India.

The activity concentrations of 238U, 232Th and 40K were found using high-resolution gamma-ray spectrometry on depth profile samples collected from the Kalaburagi districts. This study aims to ascertain the radioactivity Changes concerning the depth profile. With values of 51.64 ± 0.50 Bq kg-1 for 238U, 58.77 ± 0.23 for 232Th and 313.92 ± 3.57 for 40K, respectively, the depth profile samples of Jayanagar in the Kalaburagi region exhibit significant activity concentrations among the measured values. Moreover, estimates of the K/Th and K/U ratios have been made, based on surface-level collected samples, which may have values that differ from the samples under study.

Measurement of natural radioactivity levels in soil samples of Bidar district, Karnataka, India.

Natural radioactivity measurement, radiation monitoring of the region, dose assessment and interpretation of radiological-related parameters are crucial aspects from the public awareness and environmental safety point of view. The ionising radiations (gamma-rays) emitted from radionuclides such as 226Ra, 232Th and 40K present in environmental materials contributes significantly to the external radiation dose received by the public. High-efficiency gamma spectrometry based on a 4″ × 4″ NaI (Tl) detector was employed for estimating activity concentrations of the gamma-emitting radioelements. The spectra from the detector were recorded using a PC-based 1k multichannel analyser system (WinTMCA 32). Each sample spectrum was acquired for a counting period of 60 000 s (16.67 hr). Assuming the daughter products of 226Ra and 232Th in equilibrium, the activity concentration of these radionuclides were estimated by using the prominent gamma photo peaks of daughter products. Using the same technique, dose-related radiological parameters were calculated for all the samples. The activity concentrations of the radionuclides and the dose-related parameters for the samples were found to be comparable with the global literature values. The data generated from our study will contribute to the baseline radiological data of the region.

Study of multi-elemental concentration and nano-micro structural morphology in medicinal plants by FE-SEM and EDX method.

Medicinal plants of the Moraceae family, such as Ficus racemosa linn, have been traditionally used in the North Karnataka region for treating various ailments. This study aims to analyze the elemental composition and nano-micro structural morphology of selected species of Moraceae family medicinal plants, focusing on their potential therapeutic applications. Samples were collected from the Dharwad and Gadag districts in North Karnataka. The surface morphology at nano and micro levels was examined using a field emission scanning electron microscope, while the elemental composition was analyzed through energy-dispersive X-ray spectroscopy. The study emphasizes the detailed examination of the specific weight percent of elemental concentration and the morphological features observed. The analysis revealed fine, irregularly shaped particles with an average diameter of 20 to 50 µm on the plant surface. Elemental composition analysis showed the presence of Mg, Al, Si, Cl, K, Ca, Mn, Fe, Cu, and Zn within WHO-recommended limits.

Assessment of naturally occurring radionuclides in surface soil and drinking water from western part of Yadgir district Karnataka, India.

Radionuclide activity of the selected radionuclides 238U, 232Th and 40K was measured in surface soil samples collected from 40 villages of the western part of Yadgir district of Karnataka. A 4″ × 4″ NaI (Tl) detector based on a gamma spectrometer is used for the estimation of radionuclides. The major type of soil in this region is sandy and red. The 222Rn activity concentrations in drinking water were determined by the Emanometry method. The 222Rn activity in ground water is found to vary from 1.73 to 155.6 Bql-1. The total annual effective doses because of 222Rn inhalation and ingestion range from 4.72 to 424.84 µSv y-1 with an average value of 108.8 µSv y-1, respectively. Among the sampling stations, Shahapur and Shorapur soil samples show higher activity values than the Kembhavi and Hunasagi sampling stations soil samples.

Estimation of radioactivity in soil and drinking water samples from Northern Gulbarga District of Karnataka.

The gamma activity of the radionuclides238U, 232Th and 40K were measured in surface soil samples collected from 40 villages of Aland, Afzalpur, Ganaghapur and Kamalapur talukas of Northern Gulbarga district, Karnataka. The gamma activity of natural radionuclides were measured using 4" × 4" NaI (Tl) scintillation detector, the spectrum was analysed using a PC based 1 k MCA (winTMCA 32 scinti SPEC) and the 222Rn activity concentrations in drinking water were determined by the Emanometry method. The activity of 238U, 232Th and 40K was found to be in the range from 14.3 ± 0.3 to 64.5 ± 6.1, 15.4 ± 0.2 to 95.0 ± 4.1 and 21 ± 06 to 323 ± 09 Bq kg-1, respectively. Outdoor AED from 0.023 to 0.07 mSv y-1 and all the radiological hazards indices were well within the safe limit. The 222Rn activity in ground water is found to vary from 1.11 to 66.6 Bq l-1. The total annual effective doses due to 222Rn inhalation and ingestion range from 3.02 to 181.81 µSv y-1, respectively, with an average value of 77.18 µSv y-1.

Natural History of Very Early Onset Inflammatory Bowel Disease in North America: A Retrospective Cohort Study.

BACKGROUND: The incidence of very early onset inflammatory bowel disease (VEOIBD) is increasing, yet the phenotype and natural history of VEOIBD are not well described. METHODS: We performed a retrospective cohort study of patients diagnosed with VEOIBD (6 years of age and younger) between 2008 and 2013 at 25 North American centers. Eligible patients at each center were randomly selected for chart review. We abstracted data at diagnosis and at 1, 3, and 5 years after diagnosis. We compared the clinical features and outcomes with VEOIBD diagnosed younger than 3 years of age with children diagnosed with VEOIBD at age 3 to 6 years. RESULTS: The study population included 269 children (105 [39%] Crohn's disease, 106 [39%] ulcerative colitis, and 58 [22%] IBD unclassified). The median age of diagnosis was 4.2 years (interquartile range 2.9-5.2). Most (94%) Crohn's disease patients had inflammatory disease behavior (B1). Isolated colitis (L2) was the most common disease location (70% of children diagnosed younger than 3 years vs 43% of children diagnosed 3 years and older; P = 0.10). By the end of follow-up, stricturing/penetrating occurred in 7 (6.6%) children. The risk of any bowel surgery in Crohn's disease was 3% by 1 year, 12% by 3 years, and 15% by 5 years and did not differ by age at diagnosis. Most ulcerative colitis patients had pancolitis (57% of children diagnosed younger than 3 years vs 45% of children diagnosed 3 years and older; P = 0.18). The risk of colectomy in ulcerative colitis/IBD unclassified was 0% by 1 year, 3% by 3 years, and 14% by 5 years and did not differ by age of diagnosis. CONCLUSIONS: Very early onset inflammatory bowel disease has a distinct phenotype with predominantly colonic involvement and infrequent stricturing/penetrating disease. The cumulative risk of bowel surgery in children with VEOIBD was approximately 14%-15% by 5 years. These data can be used to provide anticipatory guidance in this emerging patient population.

Correlation of endoscopic disease severity with pediatric ulcerative colitis activity index score in children and young adults with ulcerative colitis.

AIM: To investigate of pediatric ulcerative colitis activity index (PUCAI) in ulcerative colitis correlate with mucosal inflammation and endoscopic assessment of disease activity (Mayo endoscopic score). METHODS: We reviewed charts from ulcerative colitis patients who had undergone both colonoscopy over 3 years. Clinical assessment of disease severity within 35 d (either before or after) the colonoscopy were included. Patients were excluded if they had significant therapeutic interventions (such as the start of corticosteroids or immunosuppressive agents) between the colonoscopy and the clinical assessment. Mayo endoscopic score of the rectum and sigmoid were done by two gastroenterologists. Inter-observer variability in Mayo score was assessed. RESULTS: We identified 99 patients (53% female, 74% pancolitis) that met inclusion criteria. The indications for colonoscopy included ongoing disease activity (62%), consideration of medication change (10%), assessment of medication efficacy (14%), and cancer screening (14%). Based on PUCAI scores, 33% of patients were in remission, 39% had mild disease, 23% had moderate disease, and 4% had severe disease. There was "moderate-substantial" agreement between the two reviewers in assessing rectal Mayo scores (kappa = 0.54, 95%CI: 0.41-0.68). CONCLUSION: Endoscopic disease severity (Mayo score) assessed by reviewing photographs of pediatric colonoscopy has moderate inter-rater reliability, and agreement was less robust in assessing patients with mild disease activity. Endoscopic disease severity generally correlates with clinical disease severity as measured by PUCAI score. However, children with inflamed colons can have significant variation in their reported clinical symptoms. Thus, assessment of both clinical symptoms and endoscopic disease severity may be required in future clinical studies.

Neonatal blood cultures: survey of neonatologists' practices.

BACKGROUND: There are currently no standard recommendations regarding the optimal method to obtain a blood culture in neonates. METHODS: We performed an online survey of the membership of the Section on Perinatal Pediatrics of the American Academy of Pediatrics regarding their practices when drawing blood cultures. The survey included questions regarding the type of antisepsis used in preparing the site for sampling, the amount of blood drawn and preferred site for obtaining the culture. RESULTS: Overall 715 of 2955 (24%) members responded to the survey. There was wide variability in responses to all of the questions. However, virtually all providers washed their hands and wore gloves while performing the procedure, and virtually all providers obtained ≥0.5 mL of blood for the sample. CONCLUSIONS: Given the wide variability of practices among the members of the Section, evidence-based standards are needed to guide clinical practice for this procedure.

Maternal genital bacteria and surface colonization in early neonatal sepsis.

OBJECTIVE: The study was intended to evaluate the role of maternal genital bacteria and baby's surface colonization in early onset neonatal sepsis. METHODS: Babies (born in the hospital of Jawaharlal Institute of Postgraduate Medical Education and Research) who developed clinical signs of sepsis were studied. Swabs were collected for culture from baby's umbilicus, ear, throat in addition to gastric aspirate and blood culture. The genital tract of the mother was also studied for bacterial colonization. The organisms isolated from the maternal genital tract and baby's surface colonization were correlated with those isolated from blood culture by calculating Phi correlation coefficient. RESULTS: Esch coli was the most common organism isolated from maternal genital tract and surface cultures of babies, but Klebseilla-Spp was the most common organism isolated from blood. There was a significant correlation between surface colonization of babies and maternal genital bacteria, so also was baby's surface culture and blood culture. However, correlation between maternal genital bacteria and baby's blood culture was not significant. CONCLUSION: Surface colonizing bacteria and not maternal genital bacteria are important in early onset neonatal sepsis.