Association of Anxiety and Gastrointestinal Comorbidities in Repeat Hospital Admissions in Pediatric Cyclic Vomiting Syndrome.

INTRODUCTION: Cyclic vomiting syndrome (CVS) is a functional gastrointestinal disorder with recurrent episodes of intense nausea and vomiting and thus may require frequent hospitalizations. There is paucity of data exploring the association of psychiatric and gastrointestinal comorbidities in repeat hospitalizations among pediatric patients with CVS. METHODS: We analyzed the Pediatric Health Information System database and included all patients up to 18 years of age with a diagnosis of CVS between 2016 and 2020. We excluded patients with chronic conditions, which mimic CVS. The primary outcome variable was 90-day admission rate, which was defined as a visit to emergency department or admission to observation/inpatient unit with a primary diagnosis of CVS within 90 days after an index CVS hospitalization. RESULTS: We evaluated a total of 2,604 hospitalizations represented by 1,370 unique individuals. The overall 90-day admission rate was 28.5%, which steadily decreased from 35.7% in 2016 to 23% in 2019 ( P < 0.001). Patients in the repeat hospitalization cohort were slightly older and more often men. Patients with repeat admissions had an increased proportion of anxiety and other gastrointestinal disorders. Multivariable logistic regression showed that anxiety, gastroesophageal reflux disease, functional dyspepsia, and abdominal migraine were associated with increased odds of repeat admissions. DISCUSSION: Ninety-day admission rates in pediatric CVS are decreasing overall, although still contributing to significant healthcare expenditure. Anxiety and gastrointestinal comorbidities were associated with increased risk of repeat admissions. Further prospective studies are needed to better understand the complex interactions of these comorbidities and their management affecting the natural course of CVS.

Prevalence and impact of psychiatric disorders on hospitalized pediatric patients with chronic pancreatitis.

BACKGROUND: Patients with chronic pancreatitis (CP) often have a debilitating clinical course characterized by high disease burden, and poor quality of life and these factors adversely affect mental health. However, there is paucity of literature on the prevalence and impact of psychiatric disorders on hospitalized pediatric patients with CP. METHOD: ology: We analyzed the Kids Inpatient Database, and National Inpatient Sample, between 2003 and 2019 and included patients up to 21 years of age. Pediatric CP patients with psychiatric disorders were compared with patients without any of the psychiatric disorders using the ICD diagnostic codes. Various demographic and clinical factors were compared between the groups. Length of hospitalization and total hospital charges were used as surrogates to compare the hospital resource utilization between the groups. RESULTS: We analyzed a total of 9,808 hospitalizations with CP and the overall prevalence rate of psychiatric disorders was 19.8%. The prevalence rate increased from 19.1% in 2003 to 23.4% in 2019, p = 0.006. The peak prevalence rate of 37.2% was noted at 20 years of age. Depression was noted at 7.6% of the total hospitalizations followed by substance abuse (6.5%), and anxiety (4.4%). Multivariate linear regression analysis showed that among CP patients, psychiatric disorders were independently associated with 1.3 additional days of stay and incurred $15,965 higher charges. CONCLUSIONS: The prevalence of psychiatric disorders is increasing in pediatric CP. The concomitant presence of psychiatric disorders was found to be associated with prolonged hospital stay and incurred higher healthcare charges than those CP patients without psychiatric disorders.

Gut Microbiome and Its Impact on Obesity and Obesity-Related Disorders.

PURPOSE OF REVIEW: The prevalence of overweight and obesity has been increasing worldwide at an alarming rate. Gut microbiota intimately influence host energy metabolism, and immune response. Studies indicate a prominent role of gut dysbiosis in propagating inflammation that is associated with the development of obesity and obesity-related disorders such as type 2 diabetes mellitus, metabolic syndrome, and non-alcoholic fatty liver disease. This article will review the current literature on gut microbiome and its impact on obesity and obesity-related disorders. RECENT FINDINGS: An altered gut microbial composition in obesity and obesity-related disorders is associated with enhanced energy extraction from the non-digestible dietary carbohydrates, increased gut permeability, increased production of proinflammatory metabolites, such as lipopolysaccharides, resulting in systemic inflammation and insulin resistance. Gut microbiota modulation can be achieved either by dietary manipulation or by administration of probiotics, prebiotics, synbiotics, and/or fecal microbiota transplantation aiming at the improvement of the gut dysbiosis in obesity and metabolic disorders. Further clinical trials are required to better elucidate the dose, and frequency of these interventions and also their long-term impact on host metabolism.

Increasing incidence of acute kidney injury in pediatric severe sepsis and related adverse hospital outcomes.

BACKGROUND: Pediatric severe sepsis (PSS) is associated with increased mortality, and acute kidney injury (AKI) is an independent risk factor of mortality in PSS. However, there is little data on impact of AKI on hospital outcomes in PSS. METHODS: We analyzed non-overlapping years of the Kids' Inpatient Database (KID) and National Inpatient Sample (NIS) database between 2003 and 2019 of all pediatric patients with severe sepsis between 1 and 18 years of age. Using ICD diagnosis codes, patients were divided into two groups based on AKI status and compared for outcomes measures including in-hospital mortality and healthcare resource utilization using length of stay and inflation-adjusted hospitalization charges. RESULTS: We analyzed 192,712 hospitalizations due to PSS during the 17-year period. Prevalence of AKI was 23.6% with overall increasing trend, P<0.001. Prevalence of AKI was significantly increased in patients with diabetes mellitus, organ transplantation, HIV, urinary tract anomalies, and malnutrition, P<0.001. Mortality rate was significantly higher among patients with AKI (19.8% vs. 8.1%, P<0.001). PSS with AKI had significantly higher median length of stay (14 vs. 11 days) and total hospitalization charges ($168,106 vs. 100,906), P<0.001. Multivariate logistic regression analysis showed that AKI without kidney replacement therapy (KRT) was associated with 3.02 times increased odds of mortality (95% CI 2.99-3.17, P<0.001) and those requiring KRT had 6.4 times increased odds of mortality (95%CI 6.1-6.7, P<0.001). AKI without KRT was associated with 7.7 (95% CI 7.3-8.05) additional days of hospitalization and 154,536 (95% CI 149,500-159,572) additional US dollars in hospitalization charges. CONCLUSION: Almost 1 in 4 hospitalizations with PSS had AKI and was associated with >3 times increased risk of mortality and need for KRT further adversely impacts mortality and healthcare utilization. A higher resolution version of the Graphical abstract is available as Supplementary information.

Acute Pancreatitis Is Associated with Increased Risk of In-Hospital Mortality and Health Care Utilization Among Pediatric Patients with Hematopoietic Stem Cell Transplantation.

OBJECTIVE: To analyze the impact of acute pancreatitis on mortality and hospital outcomes among the pediatric population following hematopoietic stem cell transplantation (HSCT). STUDY DESIGN: We analyzed nationally representative, nonoverlapping years of the National Inpatient Sample and Kids Inpatient Database between 2003 and 2016, including all pediatric patients who had HSCT. Patients were divided into those with and without a diagnosis of acute pancreatitis and compared for demographics, clinical characteristics, comorbid conditions related to both HSCT and acute pancreatitis, and outcome measures such as in-hospital mortality and health care resource use (length of hospital stay and total hospitalization charges). RESULTS: We analyzed a total of 128 772 hospitalizations of children and adolescents with HSCT. The overall incidence rate of acute pancreatitis was approximately 1%, with an overall increasing trend between 2003 and 2016, P < .001. The overall mortality rate was significantly greater among patients with acute pancreatitis (14.9% vs 3.6%, P < .001). Multivariate regression analysis showed that acute pancreatitis was independently associated with 3.4 times (95% CI 2.86-4.02, P < .001) increased risk of in-hospital mortality. Patients with acute pancreatitis who underwent HSCT had a greater incidence of end-organ damage and thrombotic events. Pediatric acute pancreatitis was associated with 24.3 additional days of hospitalization (95% CI 22.9-25.7, P < .001) and incurred additional $213 496 in hospitalization charges (95% CI 193 768-233 063, P < .001). CONCLUSIONS: Pediatric recipients of HSCT who develop acute pancreatitis have adverse outcomes with increased in-hospital mortality, end-organ damage, prolonged hospital stay, and greater hospitalization charges.

Role of Traditional Chinese Herbal Medicines in Functional Gastrointestinal and Motility Disorders.

PURPOSE OF REVIEW: Traditional Chinese medicine (TCM) has been in use for thousands of years in Asian countries and is rapidly gaining popularity in the Western world. Among different forms of TCM, the traditional Chinese herbal therapy and acupuncture are the most popular modalities. Here, we review the fundamentals of TCMs for clinicians practicing in the West and will also detail the evidence-based utility of Chinese herbal medicine in the management of functional gastrointestinal disorders (FGIDs). RECENT FINDINGS: In the recent decades, the popularity and usage of traditional Chinese herbal medicine in FGIDs is increasing in the West. TCMs are commonly utilized by many patients with FGIDs as the conventional therapies do have limitations such as cost, inadequate symptom control and adverse effects. The unfamiliarity of TCM philosophy among clinicians in the West, and shortage of traditional Chinese herbalists remain. The philosophy of TCM is complex and entirely different from the Western medical concepts and is difficult to understand for a clinician trained in the West. Further traditional Chinese herbal therapies are often viewed skeptically by the clinicians in the West for various reasons such as lack of scientific rigor, inconsistencies in the constituents of herbal products, and also concerns due to adverse herb effects. Future clinical trials in FGIDs should focus on herb product quality, herb-drug interactions, and standardized criteria for diagnosis and management outcomes.

Prevalence and impact of acute kidney injury in hospitalized pediatric patients with acute pancreatitis.

BACKGROUND: The incidence of acute pancreatitis (AP) in pediatric patients is rising with accompanying increased hospitalizations. Acute kidney injury (AKI) is associated with worse clinical outcomes in adults, and similar data in the pediatric age group is limited. METHODS: We analyzed non-overlapping years of National Inpatient Sample (NIS) and Kids Inpatient Database (KID) to include all patients less than 21 years old with primary diagnosis of AP between 2003 and 2016. Patients with concomitant diagnosis of AKI were compared with patients without AKI for demographics, comorbid/etiologic conditions, procedures, complications, and mortality. Length of stay and inflation-adjusted hospitalization charges were used to compare health care resource utilization. RESULTS: In total, 123,185 AP-related hospitalizations were analyzed. Overall prevalence of AKI among AP patients was 1.5% during the study period. The prevalence rate of AKI increased almost five-fold from 0.6% (2003) to a peak rate of 2.9% (2016), P < 0.001. Patients with AKI were older, more often male and had either more systemic diseases or chronic comorbid conditions such as malignancies, systemic lupus erythematosus, solid organ transplantation, hypertriglyceridemia, and hypercalcemia. Multivariate analysis demonstrated AP-related hospitalizations with AKI were 1.97 (CI 1.27-3.08, P < 0.001) times more likely to be associated with in-hospital mortality and contributed to 4.3 additional days of hospitalization (CI 4.02-4.6, P < 0.001), also incurring an additional $51,830 (CI 48571-55088, P < 0.001) in hospital charges. CONCLUSION: The prevalence of AKI is increasing steadily among pediatric patients with AP and is associated with increased risk of mortality and higher health care resource expenditure.

Successful treatment of relapsing autoimmune thrombotic thrombocytopenic purpura with rituximab.

Thrombotic thrombocytopenic purpura (TTP) is a rare but life-threatening condition characterized by thrombotic microangiopathy. The standard treatment for TTP is plasmapheresis. For refractory or relapsing cases, various immunosuppressive agents have been tried, and among them rituximab has shown promising results. TTP is rarer in the pediatric age group and the use of rituximab in children with TTP is limited. Reported herein is the successful treatment of relapsing autoimmune TTP with rituximab in a 12-year-old girl.

Cannabis use and cyclic vomiting syndrome.

None.

"Feed a Cold, Starve a Fever?" A Review of Nutritional Strategies in the Setting of Bacterial Versus Viral Infections.

PURPOSE OF REVIEW: Some data, mostly originally derived from animal studies, suggest that low glucose intake is protective in bacterial sepsis but detrimental in overwhelming viral infections. This has been interpreted into a broad belief that different forms of sepsis may potentially require different nutritional management strategies. There are a few mechanistic differences between the host interactions with virus and bacteria which can explain why there may be opposing responses to macronutrient and micronutrient during the infected state. Here, we aim to review relevant evidence on the mechanisms and pathophysiology of nutritional management strategies in various infectious syndromes and summarize their clinical implications. RECENT FINDINGS: Newer literature - in the context of the SARS-CoV-19 pandemic - offers some insight to viral infections. There is still limited clinically applicable data during infection that clearly delineate the role of nutrition during an active viral vs bacterial infections. Based on contrasting findings in different models of viruses and bacteria, the macronutrient and micronutrient needs may depend more on specific infectious organisms that may not be generalizable as bacterial versus viral. Overall, the metabolic effects of sepsis are context dependent, and various host-specific (e.g., age, baseline nutritional status, immune status, comorbidities) and illness variables (phase, duration, and severity of illness) play a significant role in determining the outcome besides pathogen-specific (virus or bacterial or fungi and combined infections) factors. Microbe therapy (probiotics and prebiotics) seems to have therapeutic potential in both viral and bacterial infected states, and this seems like a promising area for further practical research.

Impact of elexacaftor/tezacaftor/ivacaftor on lipid and fat-soluble vitamin levels and association with body mass index.

INTRODUCTION: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve gastrointestinal absorption of nutrients and may result in changes in body mass index (BMI), serum lipids, and fat-soluble vitamin levels. We hypothesized that serum lipids and vitamin levels would increase with CFTR modulator therapy and that greater increase in lipids and vitamin levels would be related to greater increase in BMI. METHODS: A retrospective study was performed to evaluate the impact of elexacaftor/tezacaftor/ivacaftor (ETI) on nutritional parameters, serum lipids, and fat-soluble vitamin levels. Pre-ETI values (<2 years prior) and post-ETI values (>1 month after) were compared. Linear regression was used to evaluate whether change in BMI is associated with the change in lipid and/or vitamin levels and whether modulator duration is associated with the degree of rise in lipid and/or vitamin levels. RESULTS: Adults and adolescents with CF (n = 137) were evaluated before and 31-300 days after starting ETI. Median BMI (adults 21.9 vs. 23.5 kg/m2 ; adolescents 48 vs. 63 percentile) increased after initiation of ETI. Total cholesterol (126 vs. 154 mg/dL), low-density lipoprotein cholesterol (63 vs. 78 mg/dL), non-high-density lipoprotein cholesterol (84 vs. 102 mg/dL), and high density lipoprotein cholesterol (43 vs. 49 mg/dL) increased after ETI, while triglycerides and very low density lipoprotein did not change. Median values for vitamin D (34.5 vs. 38.0 ng/mL) and vitamin A (40.1 vs. 47.9 µg/dL) increased, while vitamin E did not change significantly. There was no significant correlation between BMI change or duration of modulator therapy with vitamin levels or lipid changes. CONCLUSION: After initiation of ETI therapy, serum lipids increased in our population, but most values remained within the normal range. Vitamins A and D levels increased post-ETI and no changes were noted in vitamin E. No significant correlation between the degree of BMI change and the magnitude of increase in lipids or vitamin levels was found.

Severe gastric variceal bleeding successfully treated by emergency splenic artery embolization.

Bleeding from gastric varices due to splenic vein obstruction is extremely rare in children, but it can be catastrophic. Reported herein is the case of a teenager with splenic vein thrombosis and chronic decompensated liver disease from autoimmune hepatitis who presented with massive gastric variceal bleeding. Standard medical management did not control the bleeding. Due to decompensated liver disease and continuous active bleeding, emergency partial splenic artery embolization was preferred over splenectomy or a shunt procedure. Bleeding was successfully controlled by partial splenic artery embolization by decreasing the inflow of blood into the portal system. It is concluded that emergency partial splenic artery embolization is a safer alternative life-saving procedure to manage severe gastric variceal bleeding due to splenic vein obstruction in a patient with high surgical risk. To our knowledge, only one other patient with similar management has been reported in the pediatric age group.

Visual diagnosis: newborn who has unilateral color change. Diagnosis: Harlequin color change.

HCC is a benign, transient, self-limited condition encountered in neonates. Prompt recognition is required to avoid unnecessary diagnostic testing. No treatment is needed, and parental reassurance is adequate.

Exocrine Pancreatic Insufficiency in Children - Challenges in Management.

Cystic fibrosis (CF) is the leading etiology for exocrine pancreatic insufficiency (EPI) in children, followed by chronic pancreatitis, Shwachman-Diamond syndrome, and other genetic disorders. Management of EPI in children poses several unique challenges such as difficulties in early recognition, lack of widespread availability of diagnostic tests and limited number of pediatric-specific pancreatic centers. Pancreatic enzyme replacement therapy is the cornerstone of EPI management and in young children difficulties in administering pancreatic enzymes are frequently encountered. Patients with EPI also should be screened for fat-soluble vitamin deficiencies and receive appropriate supplementation. Among disorders with EPI in children, CF is the relatively well-studied condition, and most management recommendations for EPI in children come from expert consensus and conventional practice guidelines. The impact of EPI can be greater in children given their high metabolic demands and rapid growth. Early diagnosis and aggressive management of EPI prevent consequences of complications such as malnutrition, fat-soluble vitamin deficiencies, and poor bone health and improve outcomes. Management by multi-disciplinary team is the key to success.

Rising Burden of Psychiatric and Behavioral Disorders and Their Adverse Impact on Health Care Expenditure in Hospitalized Pediatric Patients with Inflammatory Bowel Disease.

Purpose: The incidence and prevalence of inflammatory bowel disease (IBD) are increasing along with an increasing number of patients with comorbid conditions like psychiatric and behavioral disorders, which are independent predictors of quality of life. Methods: Non-overlapping years (2003-2016) of National Inpatient Sample and Kids Inpatient Database were analyzed to include all IBD-related hospitalizations of patients less than 21 years of age. Patients were analyzed for a concomitant diagnosis of psychiatric/behavioral disorders and were compared with IBD patients without psychiatric/behavioral disorder diagnoses for outcome variables: IBD severity, length of stay and inflation-adjusted hospitalization charges. Results: Total of 161,294 IBD-related hospitalizations were analyzed and the overall prevalence rate of any psychiatric and behavioral disorders was 15.7%. Prevalence rate increased from 11.3% (2003) to 20.6% (2016), p<0.001. Depression, substance use, and anxiety were the predominant psychiatric disorders. Regression analysis showed patients with severe IBD (odds ratio [OR], 1.57; confidence interval [CI], 1.47-1.67; p<0.001) and intermediate IBD (OR, 1.14; CI, 1.10-1.28, p<0.001) had increased risk of associated psychiatric and behavioral disorders than patients with a low severity IBD. Multivariate analysis showed that psychiatric and behavioral disorders had 1.17 (CI, 1.07-1.28; p<0.001) mean additional days of hospitalization and incurred additional $8473 (CI, 7,520-9,425; p<0.001) of mean hospitalization charges, independent of IBD severity. Conclusion: Prevalence of psychiatric and behavioral disorders in hospitalized pediatric IBD patients has been significantly increasing over the last two decades, and these disorders were independently associated with prolonged hospital stay, and higher total hospitalization charges.

Cytomegalovirus Infection Is Associated With Adverse Outcomes Among Hospitalized Pediatric Patients With Inflammatory Bowel Disease.

Background: Adults with inflammatory bowel disease (IBD) are at increased risk of developing cytomegalovirus (CMV) colitis, which is associated with adverse outcomes. Similar studies in pediatric IBD patients are lacking. Methods: We analyzed non-overlapping years of National Inpatient Sample (NIS) and Kids Inpatient Database (KID) between 2003 and 2016. We included all patients < 21 years with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC). Patients with coexisting CMV infection during that admission were compared with patients without CMV infection for outcome measures such as in-hospital mortality, disease severity, and healthcare resource utilization. Results: We analyzed a total of 254,839 IBD-related hospitalizations. The overall prevalence rate of CMV infection was 0.3% with an overall increasing prevalence trend, P < 0.001. Approximately two-thirds of patients with CMV infection had UC, which was associated with almost 3.6 times increased risk of CMV infection (confidence interval (CI): 3.11 to 4.31, P < 0.001). IBD patients with CMV had more comorbid conditions. CMV infection was significantly associated with increased odds of in-hospital mortality (odds ratio (OR): 3.58; CI: 1.85 to 6.93, P < 0.001) and severe IBD (OR: 3.31; CI: 2.54 to 4.32, P < 0.001). CMV-related IBD hospitalizations had increased length of stay by 9 days while incurring almost $65,000 higher hospitalization charges, P < 0.001. Conclusions: The prevalence of CMV infection is increasing in pediatric IBD patients. CMV infections significantly corelated with increased risk of mortality and severity of IBD leading to prolonged hospital stay and higher hospitalization charges. Further prospective studies are needed to better understand the factors leading to this increasing CMV infection.

Impact of Erythromycin as a Prokinetic on the Gut Microbiome in Children with Feeding Intolerance-A Pilot Study.

BACKGROUND: Studies have demonstrated that the gut microbiome changes upon exposure to systemic antibiotics. There is a paucity of literature regarding impact on the gut microbiome by long-term usage of erythromycin ethyl succinate (EES) when utilized as a prokinetic. METHODS: Stool samples from pediatric patients with feeding intolerance who received EES (N = 8) as a prokinetic were analyzed for both bacteriome and mycobiome. Age-matched children with similar clinical characteristics but without EES therapy were included as controls (N = 20). RESULTS: In both groups, Proteobacteria, Firmicutes, and Bacteroidetes were the most abundant bacterial phyla. Ascomycota was the most abundant fungal phyla, followed by Basidiomycota. There were no significant differences in richness between the groups for both bacterial and fungal microbiome. Alpha diversity (at genus and species levels) and beta diversity (at the genus level) were not significantly different between the groups for both bacterial and fungal microbiome. At the species level, there was a significant difference between the groups for fungal microbiota, with a p-value of 0.029. We also noted that many fungal microorganisms had significantly higher p-values in the EES group than controls at both genera and species levels. CONCLUSIONS: In this observational case-control study, the prokinetic use of EES was associated with changes in beta diversity between the groups for mycobiome at the species level. Many fungal microorganisms were significantly higher in the EES group when compared to the controls. Confirmation of these results in larger trials will provide further evidence regarding the impact of EES on gut microbiota when utilized as a prokinetic agent.

Nutritional considerations for a new era: A CF foundation position paper.

OBJECTIVE: To provide interim advice and considerations to the CF Community around CF nutrition in the current era. METHODS: The Cystic Fibrosis (CF) Foundation organized a multidisciplinary committee to develop a Nutrition Position Paper based on the rapidly changing nutrition landscape in CF, due in part to widespread use of cystic fibrosis transmembrane regulator highly effective modulator therapy (HEMT). Four workgroups were formed: Weight Management, Eating Behavior/Food Insecurity, Salt Homeostasis and Pancreatic Enzyme use. Each workgroup conducted their own focused review of the literature. RESULTS: The committee summarized current understanding of issues pertaining to the four workgroup topics and provided 6 key take-aways around CF Nutrition in the new era. CONCLUSION: People with CF (pwCF) are living longer, particularly with the advent of HEMT. The traditional high fat, high calorie CF diet may have negative nutritional and cardiovascular consequences as pwCF age. Individuals with CF may have poor diet quality, food insecurity, distorted body image, and an higher incidence of eating disorders. An increase in overweight and obesity may lead to new considerations for nutritional management, given potential effects of overnutrition on pulmonary and cardiometabolic parameters.

Clinical case of the month. Idiopathic pulmonary hemosiderosis presenting as a rare cause of iron deficiency anemia in a toddler--a diagnostic challenge.

Iron deficiency anemia is the most common cause of anemia in all age groups. Idiopathic pulmonary hemosiderosis is an extremely rare etiology of iron deficiency anemia seen predominantly in the pediatric population. Idiopathic pulmonary hemosiderosis is characterized by the triad of symptoms consisting of iron deficiency anemia, diffuse pulmonary infiltrates, and hemoptysis. The clinical presentation is extremely variable, and all three symptoms may not always be seen. Due to the rarity of the disease and the variability in clinical presentation, diagnosis is usually delayed. Early diagnosis and treatment with corticosteroids prevents further episodes of recurrent alveolar hemorrhage and improves the clinical outcome. Hence, a high index of suspicion is required for the diagnosis of this condition in young patients presenting with severe iron deficiency anemia and diffuse pulmonary infiltrates. We report a toddler with idiopathic pulmonary hemosiderosis whose initial clinical presentation was severe iron deficiency anemia.