"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.

Cannabis use and cyclic vomiting syndrome.

None.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Update on the management of vitamins and minerals in cystic fibrosis.

Advancements in respiratory and nutrition management have significantly improved the survival of patients with cystic fibrosis (CF). With the availability of several nutrition interventions such as oral/enteral nutrition supplements, enteric-coated pancreatic enzymes, and water-miscible CF-specific vitamin supplements, frank vitamin deficiencies-with the exception of vitamin D-are rarely encountered in current clinical practice. Whereas they were previously considered as micronutrients, our current understanding of fat-soluble vitamins and minerals as antioxidants, immunomodulators, and disease biomarkers has been evolving. The impact of highly effective modulators on the micronutrient status of patients with CF remains elusive. This narrative review focuses on the updates on the management of fat-soluble vitamins and other micronutrients in CF in the current era and identifies the gaps in our knowledge.

Epidemiology of Eosinophilic Esophagitis in Patients with Cystic Fibrosis: A Population-Based 5-Year Study.

Purpose: The prevalence of eosinophilic esophagitis (EoE) has been on the rise since it was first described in the 1990s. Several diseases and exogenous factors have been associated with EoE. Our aim was to investigate the epidemiology of EoE in cystic fibrosis (CF) patients. Methods: We identified individuals with CF from September 2014 to September 2019 within a database (IBM Explorys Solutions, Inc.). The prevalence of EoE in patients with CF was compared to the general population. Results: The database included 36,111,860 patients during the 5-year study period: 12,950 with CF (0.036%) and 28,090 with EoE (0.078%). EoE prevalence was higher in CF patients than the general population (46 in 10,000 vs. 7.8 in 10,000, p<0.001). Patients with CF and EoE were more likely to be male (50% vs. 33.5%, p<0.008), children (33.3% vs. 16.5%, p<0.001), and non-Hispanic (100% vs. 88.7%, p<0.001) than CF patients without EoE. CF with EoE patients were more likely to be children than EoE only (33.3% vs. 10.5%, p<0.001). Allergic conditions were generally more prevalent in CF with EoE than CF only (83.3% vs. 68.3%, p=0.01) and EoE only (83.3% vs. 69.3%, p=0.014). Conclusion: EoE is nearly 6-times more prevalent in CF patients. Those patients had higher incidence of other atopic conditions. EoE must be considered in the differential diagnosis of patients with CF presenting with dysphagia, refractory gastroesophageal reflux, vomiting, and other esophagus-related symptoms.

Cystic fibrosis-related liver disease is an independent risk factor for mortality and increased health care resource utilization in hospitalized pediatric patients with cystic fibrosis.

BACKGROUND: Cystic fibrosis-related liver disease (CFLD) is more prevalent in recent decades due to the increasing life expectancy of patients with cystic fibrosis (CF). There is paucity of population-level data on the impact of CFLD on hospital outcomes. METHODS: We interrogated nonoverlapping years (2003-2016) of the National Inpatient Sample and Kids' Inpatient Database to include all hospitalized patients <21 years of age with a primary diagnosis of CF within the United States. A concomitant diagnosis of cirrhosis, liver fibrosis, chronic liver disease, portal hypertension, hepatomegaly, splenomegaly, hypersplenism, and liver transplant status was considered as surrogates for the diagnosis of CFLD and was compared with CF-related hospitalizations without these diagnoses (controls) for demographics, comorbid conditions, in-hospital mortality, length-of-stay, and hospital charges. RESULTS: We evaluated 94,374 CF-related hospitalizations. The prevalence of CFLD was 5.8%. The prevalence increased from 3.1% (2003) to a peak of 7.3% (2014) with an overall increasing trend, p < 0.001. Hospitalizations with CFLD had an increased prevalence of significant comorbidities: respiratory failure,lung transplant, pulmonary hypertension, diabetes mellitus, malnutrition, Clostridioides difficile infection, cholelithiasis, anemia, and need for parenteral nutrition, p < 0.001. Multivariate regression models showed CFLD as independently associated with 2.1 (95% confidence interval [CI]: 1.5 to 2.8) times increased risk of inpatient mortality, contributed to 1.1 (95% CI: 0.89 to 1.37) additional days of hospitalization, and incurring $14,852 (95% CI: 12,204 to 17,501) excess hospital charges, p < 0.001. CONCLUSION: CFLD is associated with multiple comorbidities and is independently associated with increased risk of mortality and increased health care resource utilization in pediatric CF-related hospitalizations.

Eosinophilic esophagitis in cystic fibrosis: A case series with long-term follow-up.

Challenging mealtime behaviors in young children and difficulties in meeting their dietary intake recommendations are sources of parenting stress and associated with negative quality of life. The gastrointestinal (GI) manifestations of cystic fibrosis (CF) can often present similarly to a GI pathology unrelated to CF. Specifically, this case series focuses on three toddlers with CF who presented with oral aversion and challenging mealtime behaviors and later were diagnosed with eosinophilic esophagitis (EoE). Though EoE often presents with dysphagia, younger patients commonly present with nonspecific GI symptoms such as regurgitation, emesis, abdominal pain, failure to thrive, food intolerance, and oral aversion. Given the overlap of GI manifestations in CF and EoE, it can be challenging for clinicians to diagnose the coexistent EoE in patients with CF. We describe the presenting symptoms, treatment, and successful outcomes of three pediatric patients with CF and EoE. To our knowledge, this is the second case series with a detailed description of EoE in CF.

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.