Pyloric Stenosis in a Patient with CEDNIK Syndrome.

We present a rare neurocutaneous genetic disorder where patients develop a combination of cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma, commonly known as CEDNIK syndrome. It is an autosomal recessive inheritance involving the SNAP29 protein, mapped to the 22q11.2 gene. Phenotypic variation is seen with this disease, with clinical manifestation of developmental milestone delays ranging in severity. With only a handful of documented cases, available research, management of the syndrome, and prognosis are not well established. As CEDNIK syndrome has systemic implications, care coordination between specialists is essential in improving patient outcomes. Particularly important is preventing patients from meeting the criteria of failure to thrive, a commonly reported issue. In this case, we present a four-month-old male with a past medical history of pyloric stenosis status/post pyloromyotomy who has failure to thrive, gastroesophageal reflux disease, profound hypotonia, and delayed progression of developmental milestones. Additionally, the case is complicated by idiopathic pyloric stenosis, further contributing to the patient's failure to thrive. We aim to discuss the pathophysiology of this syndrome, explore the timeline of disease progression, as well as compare our case to the current literature.

Multifocal hepatic abscess post-ERCP.

A woman in her 40s presented to hospital with cholangitis. A magnetic resonance cholangiopancreatography showed a moderately dilated common bile duct and mild intrahepatic duct dilatation with sludge. She underwent a successful endoscopic retrograde cholangiopancreatography (ERCP) and sphincteroplasty. She subsequently developed recurrence of fevers and abdominal pain with rising inflammatory markers. Initial investigations and imaging were unremarkable. A positron emission tomography scan demonstrated multiple fluorodeoxyglucose (FDG)-avid hepatic lesions, and subsequent imaging confirmed multifocal liver abscesses without a drainable collection. The patient was managed with intravenous co-amoxiclav initially before switching to oral antibiotics, however, represented 1 week later with similar symptoms. Her antibiotic coverage was broadened to intravenous pipercillin-tazobactam, and she was discharged on this with follow-up in clinic. This case report highlights the rare complication of hepatic abscesses following ERCP and the importance of considering this as a differential in patients who present with sepsis following the procedure.

Smoking status in acute myeloid leukemia is associated with worse overall survival and independent of prior nonhematopoietic malignancies, cytogenetic abnormalities, and WHO category.

Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy with several patient- and disease-associated variables known to impact prognosis. Tobacco smoking is an environmental factor associated with a greater incidence of AML, but there have been limited studies that evaluated smoking toward overall survival. We retrospectively searched for AML cases and collected clinical and diagnostic data for each case. We also used an independent next-generation sequencing (NGS) data set to assess for a distinct mutational signature associated with smoking. When stratified by smoking status, there was a greater number of males, patients aged ≥60 years, and patients with ≥2 comorbidities within the smoking category (P < .05). Survival analysis demonstrated decreased survival probability in the smokers, male smokers, smokers with 1 other comorbidity, and smokers without a prior history of nonhematopoietic malignancy (P < .05) as compared to nonsmokers. Smoking was associated with a decrease in survival within the World Health Organization categories of AML, not otherwise specified (AML NOS; P = .035) and AML with recurrent genetic abnormalities (AML RGA; P = .002). Multivariate analysis showed that patients who were smokers had a greater hazard ratio than nonsmokers after adjusting for the other covariates. Our findings demonstrated that smoking was independently associated with decreased overall survival after adjusting for other potentially confounding factors. In addition, our results suggest that a mutational signature can be recognized using NGS data in a subset of AML patients who smoke.

Prevalence of Exocrine Pancreatic Dysfunction Based on Direct Function Testing in Pediatric Inflammatory Bowel Disease.

OBJECTIVES: Patients with inflammatory bowel disease (IBD) frequently have extraintestinal manifestations. The goal of this pilot study was to assess exocrine pancreatic function in cases with suspicion for or an established diagnosis of IBD. METHODS: Direct stimulated endoscopic pancreatic function test (ePFT) was performed in 74 children with IBD, in both newly diagnosed and established cases. Demographic, clinical, and laboratory parameters were entered into a database and analyzed. RESULTS: Among the 74 children, 49 were newly diagnosed and 25 had an established diagnosis of IBD. A majority had the diagnosis of Crohn disease (CD) (n = 48; 32 new and 16 established cases) with male predominance (64.6%). Altogether, 42 (56.7%) children had either generalized or partial exocrine pancreatic insufficiency (EPI). Twenty-four of the 48 CD children (50%) had abnormal ePFT. In those with ulcerative colitis (UC), 18 of the 26 (62.9%) had abnormal ePFT. The highest abnormality rate was in lipase enzyme activity. Weight z scores were significantly lower in those with abnormal ePFT (Crohn cases: P = 0.008; UC cases: P = 0.046). Peak protein concentration in collected pancreatic fluid was significantly lower in children with CD who had abnormal ePFT ( P = 0.013). CONCLUSIONS: This pilot study revealed a relatively high prevalence of EPI in children with IBD through use of ePFT. EPI can result in maldigestion, with decreased capacity to digest fat. Further prospective studies are needed to assess need and efficacy of pancreatic enzyme replacement therapy in children with IBD and abnormal ePFT.

Assessment of exocrine pancreatic function in children and adolescents with direct and indirect testing.

The exocrine pancreas plays an important role in digestion. Understanding of the physiology and regulation of exocrine function provides insight into disease processes and basis of functional testing. Specifically, exocrine pancreatic insufficiency (EPI) can cause maldigestion and thus a proper assessment of exocrine pancreatic function is important. There are indirect and direct methods for evaluating pancreatic function. Indirect methods are varied and include stool, serum, urine, and breath tests. Fecal elastase is a commonly used indirect test today. Direct methods involve stimulated release of pancreatic fluid that is collected from the duodenum and analyzed for enzyme activity. The most used direct test today is the endoscopic pancreatic function test. Indirect pancreatic function testing is limited in identifying cases of mild to moderate EPI, and as such in these cases, direct testing has higher sensitivity and specificity in diagnosing EPI. This review provides a comprehensive guide to indirect and direct pancreatic function tests as well as an in-depth look at exocrine pancreatic function including anatomy, physiology, and regulatory mechanisms.

Development of the human pancreas and its exocrine function.

The pancreas has both endocrine and exocrine function and plays an important role in digestion and glucose control. Understanding the development of the pancreas, grossly and microscopically, and the genetic factors regulating it provides further insight into clinical problems that arise when these processes fail. Animal models of development are known to have inherent issues when understanding human development. Therefore, in this review, we focus on human studies that have reported gross and microscopic development including acinar-, ductal-, and endocrine cells and the neural network. We review the genes and transcription factors involved in organ formation using data from animal models to bridge current understanding where necessary. We describe the development of exocrine function in the fetus and postnatally. A deeper review of the genes involved in pancreatic formation allows us to describe the development of the different groups (proteases, lipids, and amylase) of enzymes during fetal life and postnatally and describe the genetic defects. We discuss the constellation of gross anatomical, as well as microscopic defects that with genetic mutations lead to pancreatic insufficiency and disease states.

Improving the quality of inpatient discharge summaries.

BACKGROUND: Discharge summaries (DCS) are vital in facilitating handover to community colleagues. Unfortunately, at Whittington Health, General Practitioners (GPs) found it difficult to identify relevant information in DCS, and use of medical jargon meant patients did not understand details of their admission. With this quality improvement project, the team aimed to improve DCS to enhance patient-centered care. OBJECTIVE: The aim of this quality improvement project (QIP) was to improve the quality of DCS by critiquing the ones produced within our trust and implementing various interventions. METHODS: Multiple Plan-Do-Study-Act (PDSA) cycles were completed. A multi-disciplinary meeting was conducted to identify the needs of each party in a DCS. A new template was subsequently launched. Teaching was conducted and educational leaflets were disseminated hospital-wide. Quality of written communication was audited quarterly, and evaluated against quality indicators. Problems with DCS were identified via GP and patient feedback, and these became the focus of subsequent PDSA cycles. RESULTS: From March 2019 to February 2020, all the audited categories improved, with an overall improvement from 67% to 92%. We also received positive feedback from GPs. CONCLUSIONS: Quality of DCS can be improved with appropriate interventions, leading to improved patient care. A similar PDSA cycle could be utilized elsewhere to achieve similar results.

Prospective Evaluation of Transanal Irrigation With a Validated Pediatric Neurogenic Bowel Dysfunction Scoring System.

OBJECTIVES: To evaluate the efficacy of transanal irrigation (TAI) in pediatric patients with neurogenic bowel dysfunction (NBD) who were treatment naïve to catheter-based TAI using Peristeen device (Coloplast). METHODS: Prospective recruitment of patients with NBD who were unsatisfied with their bowel regimen or had no bowel regimen in place, were assessed using the neurogenic bowel dysfunction score (NBDS) before initiating treatment (Time 0) with Peristeen. NBDS scores were reassessed twice: within the first 6 months (Time 1) of initiation of Peristeen and again after greater than 6 months of usage with Peristeen (Time 2). RESULTS: Over a 26-month period, 104 patients with NBD were enrolled. Mean age was 10.6 years ± 4.7 (range 3-18 years). The NBDS at Time 1 had an average reduction of 14 points from the original score. A similar trajectory was seen at Time 2, with an average reduction of 13 points from original score. There was a statistically significant decrease of 14 points, P < 0.001 at Time 1 and this response was sustained at Time 2 with a statistically significant decrease in scores from initiation by 13 points, P < 0.001. Improved patient satisfaction and quality of life with Peristeen was seen at Time 1 and Time 2. CONCLUSION: Our results suggest that Peristeen can improve quality of life in pediatric patients with NBD. Significant improvement in NBDS occurred in our pediatric patients with NBD when initiated on Peristeen. Lower scores were seen at both Time 1 and Time 2, which indicated an improvement in their overall NBD.

The Mutant Mouse Resource and Research Center (MMRRC): the NIH-supported National Public Repository and Distribution Archive of Mutant Mouse Models in the USA.

The Mutant Mouse Resource and Research Center (MMRRC) Program is the pre-eminent public national mutant mouse repository and distribution archive in the USA, serving as a national resource of mutant mice available to the global scientific community for biomedical research. Established more than two decades ago with grants from the National Institutes of Health (NIH), the MMRRC Program supports a Consortium of regionally distributed and dedicated vivaria, laboratories, and offices (Centers) and an Informatics Coordination and Service Center (ICSC) at three academic teaching and research universities and one non-profit genetic research institution. The MMRRC Program accepts the submission of unique, scientifically rigorous, and experimentally valuable genetically altered and other mouse models donated by academic and commercial scientists and organizations for deposition, maintenance, preservation, and dissemination to scientists upon request. The four Centers maintain an archive of nearly 60,000 mutant alleles as live mice, frozen germplasm, and/or embryonic stem (ES) cells. Since its inception, the Centers have fulfilled 13,184 orders for mutant mouse models from 9591 scientists at 6626 institutions around the globe. Centers also provide numerous services that facilitate using mutant mouse models obtained from the MMRRC, including genetic assays, microbiome analysis, analytical phenotyping and pathology, cryorecovery, mouse husbandry, infectious disease surveillance and diagnosis, and disease modeling. The ICSC coordinates activities between the Centers, manages the website (mmrrc.org) and online catalog, and conducts communication, outreach, and education to the research community. Centers preserve, secure, and protect mutant mouse lines in perpetuity, promote rigor and reproducibility in scientific experiments using mice, provide experiential training and consultation in the responsible use of mice in research, and pursue cutting edge technologies to advance biomedical studies using mice to improve human health. Researchers benefit from an expansive list of well-defined mouse models of disease that meet the highest standards of rigor and reproducibility, while donating investigators benefit by having their mouse lines preserved, protected, and distributed in compliance with NIH policies.

The Gut Microbiome Alterations in Pediatric Patients with Functional Abdominal Pain Disorders.

In this prospective longitudinal study, we enrolled 54 healthy pediatric controls and 28 functional abdominal pain disorders (FAPDs) pediatric patients (mean age was 11 ± 2.58 years old). Fecal samples and symptom questionnaires were obtained from all participants over the course of the year. Clinical data assessment showed that FAPDs patients were more symptomatic than the control group. Microbiome analysis revealed that Phylum Bacteroidetes was higher in FAPDs compared to the control group (p < 0.05), while phylum Firmicutes was lower in FAPDs (p < 0.05). In addition, Verrucomicrobiota was higher in the control group than the FAPDs (p < 0.05). At the genus level the relative abundance of 72 bacterial taxa showed statistically significant differences between the two groups and at the school term levels. In the control group, Shannon diversity, Observed_species, and Simpson were higher than the FAPDs (p < 0.05), and beta diversity showed differences between the two groups (PERMANOVA = 2.38; p = 0.002) as well. Using linear discriminant analysis effect size (LEfSe), Enterobacteriaceae family and Megaspherae showed increased abundances in vacation term (LDA score > 2.0, LEfSe, p < 0.05). In the FAPDs group, the severity of symptoms (T-scores) correlated with 11 different taxa bacterial relative abundances using Pearson's correlation and linear regression analyses. Our data showed that gut microbiome is altered in FAPDs compared to the control. Differences in other metrics such as alpha- and beta diversity were also reported between the two groups. Correlation of the severity of the disease (T-scores) correlated with gut microbiome. Finally, our findings support the use of Faecalibacterium/Bacteroides ratio as a potential diagnostic biomarker for FAPDs.

Efficacy of Short Course of Preksha Dhyana for Functional Abdominal Pain Disorder in a Busy Pediatric Clinic.

Introduction: Mind body techniques such as meditation improve symptoms in children and adults with IBS. Typical courses, however, are lengthy and difficult to administer. We report our experience with a short course of Preksha Dhyana (PD), a child-friendly focused meditation with yoga. Method: Physicians deliver focused meditation while medical assistants taught yoga. Three sessions were administered biweekly with recommendations for daily practice. Pain severity Likert scores were compared with a treatment as usual (TAU) historical control. Anxiety scores were compared from baseline in the PD group. Results: Thirty PD patients aged 9-17 (20 female) and 52 consecutive TAU group aged 5-17 (33 female) were reviewed. The biweekly sessions had high (71%) completion rates. Utilization rates of PD were similar to TAU despite added sessions. The PD group had an average time of follow-up of 8.9 ± 9.4 vs. 6.0 ± 3.9 months in the TAU group (p = 0.522). Changes in pain scores from baseline showed improvement in the PD group, 0.67 ± 0.13 vs. TAU 1.39 ± 0.11 (p = 0.0003). In the PD group, anxiety scores improved significantly from baseline (0.5 vs. 1, P < 0.001). Pain improved in 93% (28/30) and resolved in 47% (14/30). Conclusion: A short course of PD was successfully embedded in a busy pediatric office without additional staffing. The approach proved cost-effective without increasing overall healthcare utilization and showed significant benefits over TAU. Pending RCT confirmation, this offers a cost-effective method to incorporate mind-body techniques into a pediatric office practice.

Impact of Transanal Irrigation Device in the Management of Children With Fecal Incontinence and Constipation.

OBJECTIVES: Children with fecal incontinence and constipation can be classified into 3 groups: neurogenic bowel dysfunction (NBD) related to spinal cord defects (NBD), refractory constipation (RC), or anorectal malformations (ARMs). The transanal irrigation (TAI) device (Peristeen) was approved in 2012 by the Food and Drug Administration. This system uses a pump rather than gravity to instill water as a colonic irrigant and uses balloon occlusion of the rectum. Our aim was to evaluate the effectiveness of TAI (Peristeen) in children who failed to respond to conservative measures for stool incontinence and constipation. METHODS: Retrospective study of 147 patients prescribed TAI between January 2014 and January 2020. Data collected included demographics, prior bowel regimen, symptoms before and after, patient satisfaction scores, and NBD scores. RESULTS: Of the 147 patients initiated, 114 remain active users (13 lost to follow-up and 20 discontinued use). Multiple bowel regimens including laxatives (n = 139), cone enema (n = 40), and cecostomy (n = 7) were tried previously. The majority of our patients (n = 85) have NBD, primarily spina bifida, followed by RC (n = 43), and ARM (n = 19). For all patient groups, there was significant improvement in symptoms of fecal incontinence and constipation (P ≤ 0.001). Abdominal pain was improved in the NBD and RC group, but not significantly in the ARM group. CONCLUSIONS: We provide a single-center review of a large pediatric cohort using TAI (Peristeen) for management of fecal incontinence and constipation. Peristeen offered significant improvement in patients with NBD, RC, and ARM.

Isolated Amylase Deficiency in Children and Its Clinical Implication.

OBJECTIVES: Among the 3 lines of pancreatic enzymes, amylase secretion develops last and it is not detected in duodenal aspirates of infants in the first month after birth. The aim of this study was to assess the prevalence and symptoms of isolated amylase deficiency in children. METHODS: During a 6-year period, we performed endoscopic pancreatic function tests (ePFT) in 712 children. Isolated amylase deficiency was defined as activity that was below the third percentile of our referenced population with normal lipase and protease activities. RESULTS: Seventy-two children between age 0.21 and 15.7 years (boys, n = 35) had isolated amylase deficiency. The highest prevalence of isolated amylase deficiency was found in patients less than 6 months of age (52.9%). From 6 months to 1 year of age, the prevalence was 40%. The prevalence gradually decreased until 18 months. Failure to thrive, poor weight gain, diarrhea, and abdominal bloating were the most frequent indications for ePFT. Eleven children had repeat ePFT after initial diagnosis and 6 had normal enzyme activity, whereas 5 had remained amylase-deficient an average of 1.65 years later. CONCLUSIONS: The prevalence of selective amylase deficiency was 10.1% in the 712 children who underwent ePFT with the suspicion of malabsorption. Low amylase activity is "physiologic" in infants <6 months of age, however, this study supports that it should be considered in the differential diagnosis in children older than 6 months of age.

The role of psychological factors in pediatric functional abdominal pain disorders.

BACKGROUND: Pediatric functional abdominal pain disorders (FAPDs) are disorders of brain-gut dysregulation. Psychological factors are known to be related to etiology, maintenance, and exacerbation of pediatric FAPDs. With the evolving literature in the past two decades, a better understanding has emerged of precisely which psychological factors are associated with childhood FAPDs. PURPOSE: This narrative literature review summarizes the literature of both child and parent psychological factors in pediatric FAPD. Where anxiety and depression were major targets in the older literature, present-day focus is increasingly on pain-specific cognitions and coping strategies including disease threat and catastrophizing. In addition, parental reaction to a child's pain is increasingly recognized as an important moderator of a child's outcomes and has become an area for clinical intervention. Screening for these factors and integrative treatment approaches are recommended in childhood FAPD.

Association between continuous peripheral i.v. infusion of 3% sodium chloride injection and phlebitis in adults.

PURPOSE: One institution's experience with use of peripheral i.v. (PIV) catheters for prolonged infusions of 3% sodium chloride injection at rates up to 100 mL/hr is described. METHODS: A prospective, observational, 13-month quality assurance project was conducted at an academic medical center to evaluate frequencies of patient and catheter phlebitis among adult inpatients who received both an infusion of 3% sodium chloride injection for a period of ≥4 hours through a dedicated PIV catheter and infusions of routine-care solutions (RCSs) through separate PIV catheters during the same hospital stay. RESULTS: Sixty patients received PIV infusions through a total of 291 catheters during the study period. The majority of patients (78%) received infusions of 3% sodium chloride injection for intracranial hypertension, with 30% receiving such infusions in the intensive care unit. Phlebitis occurred in 28 patients (47%) during infusions of 3% sodium chloride and 26 patients (43%) during RCS infusions (p = 0.19). Catheter phlebitis occurred in 73 catheters (25%), with no significant difference in the frequencies of catheter phlebitis with infusion of 3% sodium chloride versus RCSs (30% [32 of 106 catheters]) versus 22% [41 of 185 catheters]), p = 0.16). CONCLUSION: Patient and catheter phlebitis rates were not significantly different with infusions of 3% sodium chloride injection versus RCSs, suggesting that an osmolarity cutoff value of 900 mOsm/L for peripheral infusions of hypertonic saline solutions may not be warranted.

Allergic reactions associated with pegaspargase in adults.

One of the severe toxicities of pegaspargase (PEG) is the development of allergic reactions. This study retrospectively assessed 311 PEG doses administered to 139 acute lymphoblastic leukemia patients from May 1, 2008 to July 30, 2014 for allergic reactions based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Fourteen reactions were recorded in 13 patients (9.4%). The rate of reaction did not differ between patients who received pre-medications and those who did not (p = 0.939). Patients who received only IV PEG doses had a higher rate of reaction compared to only IM PEG (14.0% vs 1.6%; p = 0.010). Six of the seven patients with CTCAE grade 4 reactions received a majority of IV doses, suggesting that severity of reactions may increase with IV administration. Capped doses at 3750 units only had a reaction rate of 2.3%, while uncapped doses over 3750 units were found to have a 6.0% reaction rate (p = 0.194).

Fosaprepitant for the Treatment of Refractory Postoperative Nausea and Vomiting.

Postoperative nausea and vomiting (PONV) is a debilitating condition that occurs in approximately 30% of patients undergoing general anesthesia. Premedication with 5-HT3 receptor antagonists and glucocorticoids is effective in clinical practice; however, 10% to 20% of patients still develop PONV. Currently, little is known about the treatment of refractory PONV. We present a case that illustrates the use of fosaprepitant for the treatment of refractory postoperative nausea and vomiting.

Rupture of the maternal renal calyx secondary to fetal malpresentation: a case report.

BACKGROUND: Rupture of the renal collecting system is a potentially life-threatening condition in pregnancy. Most cases are associated with obstruction from nephrolithiasis or diseased renal parenchyma. CASE: A 24-year-old, nulliparous, African American woman at 38 weeks + 3 days' gestation presented with left flank pain refractory to conservative pain management. Computed tomography was negative for a stone but significant for infrarenal fluid and rupture of a left renal calyx. The fetal head was not flexed and appeared to be compressing the left ureter. A face presentation became apparent during her labor course, and she underwent a cesarean delivery when labor did not progress. CONCLUSION: This represents the first reported case of a ruptured renal collecting system secondary to fetal malpresentation. A high index of suspicion is essential to diagnose collecting system rupture, and it may occur in the absence of parenchymal disease or stones.

Treatment of acute myeloid leukemia during pregnancy.

OBJECTIVES: Systematically review the literature assessing outcomes of acute myeloid leukemia (AML) treatment during pregnancy. DATA SOURCES: A Pubmed literature search (January 1969 to June 2014) for articles written about AML and pregnancy, and bibliographies/citations of previously published reviews. STUDY SELECTION AND DATA EXTRACTION: Articles written in the English language that administered active AML chemotherapy during pregnancy were included. DATA SYNTHESIS: Eighty-five fetuses were exposed to chemotherapy from 83 mothers: 8 mothers began induction chemotherapy in the first trimester, 61 mothers in the second trimester, and 14 mothers in the third trimester. Chemotherapy resulted in more fetal deaths and spontaneous abortions during the first trimester (37.5%) compared with the second (9.7%) and third trimesters (0%). All cases included cytarabine; 47 fetuses were exposed to daunorubicin and 8 fetuses to idarubicin. The percentages of fetal defects and death for cytarabine and daunorubicin combinations were 8.5% and 6.4%, respectively. With cytarabine and idarubicin combinations, the percentages of fetal defects and death were 28.6% and 12.5%, respectively. Complete remission (CR) rates were 100%, 81%, and 67% in the first, second, and third trimesters. CONCLUSIONS: Treatment during the second and third trimesters resulted in fewer fetal complications than the first trimester. However, delaying AML treatment may adversely affect the mother's outcomes. In the reported cases, induction during pregnancy resulted in CR rates comparable to that in nonpregnant patients. The choice of anthracycline is still unclear, but the decision should be made with careful consideration, weighing the outcomes for the mother and fetus.