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Background: Therapeutic endoscopic procedures are increasingly necessary for children. Pediatric gastroenterologist training and experience with endoscopic hemostasis and other complex therapeutic endoscopy procedures are often limited. We evaluated the impact of the implementation of an advanced complex endoscopy (ACE) team, which provides 24/7 inpatient/outpatient back-up endoscopy support., Methods: We analyzed hemostasis quality outcomes in the 2 years before implementation of ACE (2018-2020) versus the year following the implementation of ACE (2020-2021). We analyzed pediatric gastroenterology provider satisfaction and perspectives with a survey that was distributed to faculty, fellows, and advanced practice providers 1 month before implementation of ACE and again 12 months following ACE implementation., Results: Endoscopy volume and outcome metrics for hemostasis procedures, including latency to endoscopy, need for reintervention, and administration/diversity of hemostatic therapy, including multimodal therapy, improved in the year following implementation of the ACE (p < 0.05 for each). Survey results demonstrated a positive impact on provider endoscopy experience and high utilization of ACE. Twenty-two percent of providers reported activating ACE in the prior month and 66% in the prior year. Most providers who activated ACE were very satisfied (85%) or satisfied (7.7%). Eighty-three percent noted ACE had a positive impact on inpatients, and 50% noted a positive impact on outpatient endoscopy. Provider anxiety with endoscopy diminished post-ACE implementation (62% vs. 28%). Respondents unanimously found ACE beneficial to patient care (100%)., Conclusions: ACE implementation was associated with improved provider perspectives surrounding endoscopy and significant improvement in hemostasis quality parameters, escalation of hemostasis procedure volume, and broadening the range of hemostasis interventions., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Abstract: High-frequency ultrasound is the imaging modality of choice for evaluating penile pathology because of its easy access, low cost, and patient tolerance ( The Penis, Diagnostic Ultrasound, second edtion . Boca Raton: CRC Press; 2007:957-978). This pictorial review will illustrate the sonographic features of emergent and nonemergent penile conditions such as penile fracture, spongial tear, urethral injury, various types of priapism, erectile dysfunction, penile abscess, and Mondor disease., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Eosinophilic esophagitis (EoE) is an immune-mediated inflammatory disease characterized by eosinophilic infiltration of esophageal tissue. Subtyping of EoE patients could be useful in predicting therapeutic response. We propose clinical subtypes, apply them to our pediatric EoE population retrospectively, and assess therapy choices and remission at one year., Methods: A retrospective chart review of pediatric patients diagnosed with EoE was conducted. Patients were grouped into proposed subtypes (severe, allergic, fibrostenotic, inflammatory, unclassified) based on presenting characteristics. The primary outcome was histologic remission, which was defined &lt;15 eosinophils/high-powered-field (hpf) at the closest visit 1 year postdiagnosis., Results: Subtyping was possible in 242 of 256 patients and follow-up histological data were available in 75 subjects. The majority had an overlap in phenotype with 17% severe, 77% allergic, 15% fibrostenotic, 60% inflammatory, and 5% unclassified, whereas 45% of the cohort were assigned to a unique subtype. At 1 year, 43/75 (57%) of patients achieved histologic remission, with an overall average decrease of 33 (IQR -47, -12) eosinophils/hpf across the entire cohort. There was no difference in remission rates among subtypes. First-line therapy review revealed higher rates of proton pump inhibitor (PPI) ± topical steroids utilization in severe patients, while topical steroids were prescribed preferentially over dietary therapy in the fibrostenotic subtype., Conclusion: There were no observed differences in remission rates at 1 year among clinically defined subtypes of EoE, although this could be attributed to overlapping subtypes. Most patients responded well to medical therapy. Larger scale prospective studies designed to subtype patients and protocolize treatment may help personalize the approach to EoE management., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Inflammatory bowel diseases are costly chronic gastrointestinal diseases. We aimed to determine whether immediate colectomy with ileal pouch-anal anastamosis (IPAA) after diagnosis of severe ulcerative colitis (UC) was cost-effective compared to the standard medical therapy., Methods: We created a Markov model simulating 2 cohorts of 21-year-old patients with severe UC, following them until 100 years of age or death, comparing early colectomy with IPAA strategy to the standard medical therapy strategy. Deterministic and probabilistic analyses were performed., Results: Standard medical care accrued a discounted lifetime cost of $236,370 per patient. In contrast, early colectomy with IPAA accrued a discounted lifetime cost of $147,763 per patient. Lifetime quality-adjusted life-years gained (QALY-gained) for standard medical therapy was 20.78, while QALY-gained for early colectomy with IPAA was 20.72. The resulting incremental cost-effectiveness ratio (Δcosts/ΔQALY) was approximately $1.5 million per QALY-gained. Results were robust to one-way sensitivity analyses for all variables in the model. Quality-of-life after colectomy with IPAA was the most sensitive variable impacting cost-effectiveness. A low utility value of less than 0.7 after colectomy with IPAA was necessary for the colectomy with IPAA strategy to be cost-ineffective., Conclusions: Under the appropriate clinical settings, early colectomy with IPAA after diagnosis of severe UC reduces health care expenditures and provides comparable quality of life compared to exhaustive standard medical therapy.

Background: Inflammatory bowel diseases (IBDs) are costly chronic gastrointestinal diseases, with pediatric IBD representing increased costs per patient compared to adult disease. Health care expenditures for ulcerative colitis (UC) are >$2 billion annually. It is not clear whether the addition of VSL#3 to standard medical therapy in UC induction and maintenance of remission is a cost-effective strategy., Patients and Methods: We performed a systematic review of the literature and created a Markov model simulating a cohort of 10-year-old patients with severe UC, studying them until 100 years of age or death. We compared 2 strategies: standard medical therapy versus medical therapy + VSL#3. For both strategies, we assumed that patients progressed through escalating therapies--mesalamine, azathioprine, and infliximab--before receiving a colectomy + ileal pouch anal anastamosis (IPAA) if the 3 medical therapy options were exhausted. The primary outcome measure was the incremental cost-effectiveness ratio (ICER), defined as the difference of costs between strategies for each quality-adjusted life-year (QALY) gained. One-way sensitivity analyses were performed on variables to determine the key variables affecting cost-effectiveness., Results: Standard medical care accrued a lifetime cost of $203,317 per patient, compared to $212,582 per patient for medical therapy + VSL#3. Lifetime QALYs gained was comparable for standard medical therapy and medical therapy + VSL#3 at 24.93 versus 25.05, respectively. Using the definition of ICER <50,000/QALY as a cost-effective intervention, medical therapy + VSL#3 produced an ICER of $79,910 per QALY gained, making this strategy cost-ineffective. Sensitivity analyses showed that 4 key parameters could affect the cost-effectiveness of the 2 strategies: cost of colectomy + IPAA, maintenance cost after surgery, probability of developing pouchitis after surgery, and the quality of life after a colectomy + IPAA. High surgical and postsurgical costs, a high probability of developing pouchitis, and a low quality of life after a colectomy + IPAA could make adjunct VSL#3 use a cost-effective strategy., Conclusions: Given present data, adjunct VSL#3 use for pediatric UC induction and maintenance of remission is not cost-effective, although several key parameters could make this strategy cost-effective. The quality of life after an IPAA is the single most important variable predicting whether this procedure benefits patients over escalating standard medical therapy.

Background and Aim: Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder characterized by upper gastrointestinal symptoms and the presence of high numbers of eosinophils in the esophagus. Although eosinophils in the esophagus have been found to be activated in subjects with EoE, detailed studies of intracellular signaling pathways involved in the mechanism of activation of eosinophils in EoE have heretofore been limited. The aim of the study was to assess whether any surface molecules or transcription factors are activated in peripheral eosinophils in subjects with EoE., Methods: Eosinophils and CD3+ lymphocytes were identified directly from 50 μL of whole blood of EoE and control subjects. Using Hi-FACS, levels of surface activation markers, including CD66b, and intracellular phosphoepitopes, including phosphorylated forms of signal transducer and activator of transcription (phospho-STAT) 1 and 6, were measured within each cell subset., Results: Levels of surface CD66b as well as levels of intracellular phospho-STAT1 and phospho-STAT6 in peripheral blood eosinophils were significantly higher for untreated subjects with EoE vs healthy controls (P < 0.05). Levels of phospho-STAT1 and phospho-STAT6 in peripheral blood eosinophils were lower in subjects with EoE on therapy versus untreated subjects with EoE (P < 0.05)., Conclusions: Levels of phospho-STAT1 and phospho-STAT6, transcription factors involved in inflammatory processes, were both significantly higher in peripheral eosinophils from untreated (ie, newly diagnosed) subjects with EoE versus subjects with EoE on therapy, healthy controls. Blood-based measurements of CD66b and phospho-STAT levels in peripheral eosinophils may be beneficial for identifying EoE.

Objective: The aim of the study was to investigate whether eosinophils have increased human leukocyte antigen (HLA)-DR expression in subjects with eosinophilic esophagitis (EoE) compared with controls., Patients and Methods: Patients who were undergoing an upper endoscopy with biopsies for suspected gastroesophageal reflux disease (GERD) or EoE at Lucile Packard Children's Hospital were enrolled. In total, the blood and tissue samples of 10 healthy controls (HC), 11 subjects with GERD, and 10 with EoE were studied. Multiple tissue staining to identify eosinophils (via eosinophil cationic protein-clone EG2) and major histocompatibility complex class II cell surface receptors (via HLA-DR) was performed via immunohistochemistry. The peripheral blood was analyzed using flow cytometry to detect eosinophil HLA-DR expression among these subjects., Results: In the tissue, a greater proportion of eosinophils expressed HLA-DR among the subjects with EoE (mean 0.83 +/- 0.14, n = 9) relative to those with GERD (mean 0.18 +/- 0.19, n = 8, P < 0.01) and HC (mean 0.18 +/- 0.13, n = 6, P < 0.01). In total, 6 participants (4 HC subjects and 2 subjects with GERD) did not have any eosinophils identified on tissue staining and were unable to be included in the present statistical analysis. In the blood, there was no statistically significant difference in eosinophil HLA-DR expression among HC subjects (mean 415 +/- 217, n = 6), subjects with GERD (mean 507 +/- 429, n = 2), and those with EoE (mean 334 +/- 181, n = 6)., Conclusions: These data demonstrate that the eosinophils from the esophagus of subjects with EoE have increased HLA-DR expression within this tissue.

Objectives: There are limited data on the role of regulatory T cells (Treg) in the disease pathology of eosinophilic esophagitis (EoE). We tested the differences in Treg in subjects with EoE compared with those with gastroesophageal reflux disease (GERD) and healthy controls (HC)., Patients and Methods: Pediatric patients evaluated by endoscopy were recruited for our study. Participants were categorized into 3 groups: EoE, GERD, and HC. RNA purified from esophageal biopsies were used for real-time quantitative polymerase chain reaction assays and tested for forkhead box P3 (FoxP3) mRNA expression. Treg were identified as CD4+CD25hiCD127lo cells in peripheral blood and as CD3+/FoxP3+cells in esophageal tissue., Results: Forty-eight subjects were analyzed by real-time quantitative polymerase chain reaction: EoE (n = 33), GERD (n = 7), and HC (n = 8). FoxP3 expression was higher by up to 1.5-fold in the EoE group compared with the GERD and HC groups (P < 0.05). Protein levels of FoxP3 in blood and tissue were then investigated in 21 subjects: EoE (n = 10), GERD (n = 6), and HC (n = 5). The percentage of Treg and their subsets in peripheral blood were not significant between groups (P > 0.05). The amount of Treg in esophageal tissue was significantly greater in the EoE group (mean 10.7 CD3+/FoxP3+cells/high power field [HPF]) compared with the other groups (GERD, mean 1.7 CD3+/FoxP3+cells/HPF and HC, mean 1.6 CD3+/FoxP3+cells/HPF) (P < 0.05)., Conclusions: We show that Treg are increased in esophageal tissue of EoE subjects compared with GERD and HC subjects. The present study illustrates another possible mechanism involved in EoE that implicates impairment of immune homeostasis.

Objective: To examine the morphology and motility of the distal small bowel of infants with rotavirus gastroenteritis using non-invasive/non-ionizing imaging technology., Methods: Prospective, non-randomized observational study of five infants with symptomatic rotavirus infection. Infants were imaged by real-time magnetic resonance imaging (MRI) and ultrasound within 5 days of onset of gastroenteritis symptoms. Imaging studies were repeated in the convalescent period 5 to 9 weeks later., Results: Three of five infants had a significant increase in the ileal wall thickness visualized by ultrasound during acute rotavirus infection compared with convalescence. The number and size of mesenteric lymph nodes visualized by ultrasound appeared similar in the acute and convalescent phases, as did peristaltic activity assessed by MRI., Conclusion: Abdominal ultrasound can detect changes in ileal wall thickness in infants with rotavirus infection. These changes may reflect ileal inflammation elicited by viral infection. Such studies may prove useful in evaluating morphologic response to attenuated rotavirus vaccines.

Objective: To assess familial cardiovascular risk factors in women developing hypertension in pregnancy., Method: Of 2211 women delivering live births after enrollment in a pregnancy cohort study, 85 (3.8%) developed preeclampsia (antepartum systolic blood pressure greater than 140 or diastolic blood pressure greater than 90 plus proteinuria) and 142 (6.4%) developed transient hypertension of pregnancy (antepartum blood pressure elevation without proteinuria). At a mean of 10.2 weeks' gestation, women were asked about first-degree family members with heart disease or stroke, hypertension, diabetes, renal disease, or any of these, which defined familial cardiovascular risk., Results: After adjustment for age and body size, having two or more family members, versus no family members, with cardiovascular risk imparted a 1.9-fold (95% confidence interval [CI] 1.1, 3.2) elevated risk for developing preeclampsia and a 1.7-fold (95% CI 1.1, 2.6) risk for developing transient hypertension of pregnancy. Having two or more family members with hypertension also imparted a significant, two-fold elevation in risk of preeclampsia and transient hypertension of pregnancy, and having two or more family members with heart disease or stroke imparted a 3.2-fold (95% CI 1.4, 7.7) elevation in the risk for preeclampsia., Conclusion: A strong family history of aggregate cardiovascular risk increased the likelihood for developing preeclampsia and transient hypertension of pregnancy. These findings support the theory that a preexisting tendency to cardiovascular risk, and particularly hypertension, increases a women's susceptibility to developing hypertension in pregnancy.

We studied the characteristics and temporal trends of AIDS- associated non-Hodgkin's lymphoma (AIDS-NHL) in individuals with hemophilia. Prospective data were collected on 33 HIV-positive hemophiliacs with AIDS-NHL enrolled in the Hemophilia Malignancy Study (HMS), of whom 21 had primary and 12 had secondary or subsequent AIDS-defining illnesses, and analyzed for frequency and temporal trends. As compared with primary AIDS- NHL, secondary AIDS-NHL occurred at an older mean age, 37 versus 29 years (p = 0.12); at a lower mean CD4 count, 46 versus 154 (p = 0.07); after a longer period of immunosuppression (CD4 < 200/microl), 41 versus 16 months (p = 0.03); and with shorter median survival, 2 versus 7 months (p = 0.09). The presence of EBV in tumor tissue was associated with shorter survival, 1 versus 7 months (p = 0.17). Between 1981 and 1988 and 1989 and 1994, the proportion of primary AIDS diagnoses that were AIDS-NHL changed minimally, 4.6 versus 6.1%, whereas there were significant decreases in Pneumocystis carinii pneumonia (PCP, p = 0.02) and wasting (p = 0.07), and an increase in Candida (p = 0.004). These findings confirm that an increasing proportion of AIDS-NHL in hemophiliacs are occurring as secondary or later AIDS diagnoses, and they are associated with prolonged duration of immunosuppression.

Background: The minimum alveolar concentration (MAC) of volatile anesthetics is decreased during pregnancy, but MAC in the early postpartum period has not been reported. The aim of this study was to determine the MAC of isoflurane and to evaluate the relation between MAC and serum progesterone and beta-endorphin in patients after delivery., Methods: Eight patients undergoing elective bilateral tubal ligation during general anesthesia in the early postpartum period (< 12 h postpartum) and eight patients undergoing this procedure in the late postpartum period (12-25 h postpartum) were studied. Eight patients undergoing bilateral tubal ligation more than 6 weeks after delivery served as control subjects. Anesthesia was induced with propofol and maintained with isoflurane in oxygen to a steady end-tidal concentration of 0.8-1.0 vol% for 10 min. Reaction to a standardized electric stimulation applied to the forearm was graded as positive (gross or delayed movement) or negative. By using the bracketing technique, the concentration of isoflurane was increased or decreased by 0.1 vol%, depending on the positive or negative responses., Results: The MAC (mean +/- SD) in patients in the early postpartum period was significantly less (0.75 +/- 0.17 vol%) than that in control subjects (1.04 +/- 0.12 vol%; P < 0.01) and that in patients in the late postpartum period (0.95 +/- 0.2 vol%; P < 0.05). The difference in MAC values between late postpartum and control was not significant (P > 0.05). There was an inverse correlation between progesterone concentration postpartum and time after delivery (r = -0.527; P = 0.036), but P = 0.744). There was no correlation between plasma progesterone or beta-endorphin and MAC by multiple regression (r = 0.166; P = 0.950)., Conclusions: Isoflurane MAC remains 28% less than normal within the 1st 12 h postpartum and then returns to normal 12-25 h after delivery.

A randomized clinical trial in adult ALL has previously shown a benefit for central nervous system prophylaxis (intrathecal methotrexate plus cranial irradiation) with respect to CNS relapse-free interval, and the long-term follow-up revealed that about 20% of the patients in this multicenter trial were long survivors, probably cured. Questions that were not addressed in the earlier reports concern the time to CNS relapse as the initial site of relapse and the prognostic factors associated with initial CNS relapse. Further analysis of the 62 evaluable randomized patients has shown that in every case with CNS relapse, time to any relapse and time to CNS relapse as the first event were the same. Multivariate analysis showed that, although CNS prophylaxis is a significant favorable prognostic factor with respect to CNS relapse over time, race (nonwhite is unfavorable) and splenomegaly (unfavorable) are more significant, albeit not well explained. Future trials should examine race and splenomegaly as well as other clinical and biologic features as potential prognostic factors for CNS relapse in adult ALL.