Therapeutic potential of Pien Tze Huang in colitis-associated colorectal cancer: mechanistic insights from a mouse model.

BACKGROUND: Pien Tze Huang (PZH), a traditional Chinese medicine formulation, is recognized for its therapeutic effect on colitis and colorectal cancer. However, its protective role and underlying mechanism in colitis-associated colorectal cancer (CAC) remain to be elucidated. METHODS: A CAC mouse model was established using AOM/DSS. Twenty mice were randomly divided into four groups (n = 5/group): Control, PZH, AOM/DSS, and AOM/DSS + PZH groups. Mice in the PZH and AOM/DSS + PZH group were orally administered PZH (250 mg/kg/d) from the first day of experiment, while the control and AOM/DSS group received an equivalent volume of distilled water. Parameters such as body weight, disease activity index (DAI), colon weight, colon length, colon histomorphology, intestinal tumor formation, serum concentrations of pro-inflammatory cytokines, proliferation and apoptosis in colon tissue were assessed. RNA sequencing was employed to identify the differentially expressed transcripts (DETs) in colonic tissues and related signaling pathways. Wnt/ß-Catenin Pathway-Related genes in colon tissue were detected by QPCR and immunohistochemistry (IHC). RESULTS: PZH significantly attenuated AOM/DSS-induced weight loss, DAI elevation, colonic weight gain, colon shortening, histological damage, and intestinal tumor formation in mice. PZH also notably decreased serum concentration of IL-6, IL-1ß, and TNF-α. Furthermore, PZH inhibited cell proliferation and promote apoptosis in tumor tissues. RNA-seq and KEGG analysis revealed key pathways influenced by PZH, including Wnt/ß-catenin signaling pathway. IHC staining confirmed that PZH suppressed the expression of ß-catenin, cyclin D1 and c-Myc in colonic tissues. CONCLUSIONS: PZH ameliorates AOM/DSS-induced CAC in mice by suppressing the activation of Wnt/ß-catenin signaling pathway.

Standardizing steroid protocols for newly diagnosed inflammatory bowel disease patients: A quality improvement initiative.

OBJECTIVES: Systemic steroids can be used for induction of inflammatory bowel disease (IBD), but are not recommended as long-term therapy. Steroid weaning requires rigorous monitoring of symptoms, which may be cumbersome and lead to missed opportunities. We aim to describe our local quality improvement (QI) initiative to improve and standardize the steroid weaning process. METHODS: After identifying drivers of steroid weaning, a protocol was developed and implemented for newly diagnosed IBD patients started on steroids and subsequently initiated on anti-TNF-α therapy. Interventions included development of a tapering schedule, and standardizing communication with patients and evaluation of symptoms. The primary aim was to increase the percent of patients called on a weekly basis by 20%; secondary aims were to decrease the median steroid days by 25% and to increase the number of our patients weaned off steroids at 8 weeks from 35% to 75% by 1 year after the initiative. RESULTS: The median percent of patients called on a weekly basis to assess clinical symptoms and to wean steroids increased to 80% after 1 year. The median number of systemic corticosteroid days decreased from 67.5 to 50.5 days post-protocol implementation with 61.1% patients weaned off by 8 weeks from discharge. Zero patients were admitted for flares with the protocol implementation. CONCLUSION: Our experience illustrates that QI methodology can be used successfully to improve and standardize the steroid weaning process, leading to shortened steroid duration and without increased flares and hospitalizations.

Comparison of budesonide vehicles in inducing histologic remission in pediatric eosinophilic esophagitis.

OBJECTIVES: Oral viscous budesonide (OVB) is a common medication used to treat eosinophilic esophagitis (EoE). It is typically mixed with Splenda to produce a slurry, but other delivery vehicles have been used in clinical practice. We aimed to evaluate outcomes of pediatric EoE patients treated with OVB using different drug delivery vehicles. METHODS: We performed a retrospective chart review of pediatric EoE patients treated with OVB. The primary aim was to evaluate rates of histologic remission (defined by <15 eosinophils per high power field in both mid and distal esophagus) after 6-12 weeks of OVB treatment for each delivery vehicle. Secondary aims were to evaluate histologic response and endoscopic response and remission of different delivery vehicles, and to compare the efficacy of different treatment regimens. RESULTS: A total of 111 patients were included in the study. Median treatment duration was 3.4 months. Overall rate of histologic remission with OVB was 52.6%. There was no difference in rates of histologic remission (p = 0.313) or response (p = 0.195 and p = 0.681 in mid and distal esophagus, respectively) among the different vehicle types or treatment regimens. Similarly, there was no difference in endoscopic remission and response among the different vehicle types (p = 0.853 and p = 0.727) or treatment regimens (p = 0.244 and p = 0.157). Patients who achieve histologic remission were more likely to be non-Hispanic Caucasian. CONCLUSION: Our findings suggest there is no difference in histologic and endoscopic outcomes with various delivery vehicles or combination therapy with OVB in the treatment of EoE. More palatable and cost-effective vehicles can be used to treat EoE.

Qing Hua Chang Yin ameliorates chronic colitis in mice by inhibiting PERK-ATF4-CHOP pathway of ER stress and the NF-κB signalling pathway.

CONTEXT: Ulcerative colitis has been clinically treated with Qing Hua Chang Yin (QHCY), a traditional Chinese medicine formula. However, its precise mechanisms in mitigating chronic colitis are largely uncharted. OBJECTIVE: To elucidate the therapeutic efficiency of QHCY on chronic colitis and explore its underlying molecular mechanisms. MATERIALS AND METHODS: A total ion chromatogram fingerprint of QHCY was analysed. Chronic colitis was induced in male C57BL/6 mice using 2% dextran sodium sulphate (DSS) over 49 days. Mice were divided into control, DSS, DSS + QHCY (0.8, 1.6 and 3.2 g/kg/d dose, respectively) and DSS + mesalazine (0.2 g/kg/d) groups (n = 6). Mice were intragastrically administered QHCY or mesalazine for 49 days. The changes of disease activity index (DAI), colon length, colon histomorphology and serum pro-inflammatory factors in mice were observed. RNA sequencing was utilized to identify the differentially expressed transcripts (DETs) in colonic tissues and the associated signalling pathways. The expression of endoplasmic reticulum (ER) stress-related protein and NF-κB signalling pathway-related proteins in colonic tissues was detected by immunohistochemistry staining. RESULTS: Forty-seven compounds were identified in QHCY. Compared with the DSS group, QHCY significantly improved symptoms of chronic colitis like DAI increase, weight loss, colon shortening and histological damage. It notably reduced serum levels of IL-6, IL-1ß and TNF-α. QHCY suppressed the activation of PERK-ATF4-CHOP pathway of ER stress and NF-κB signalling pathways in colonic tissues. DISCUSSION AND CONCLUSIONS: The findings in this study provide novel insights into the potential of QHCY in treating chronic colitis patients.

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.

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.

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.

Differences in Clinical Presentation of Eosinophilic Esophagitis in Pediatric Patients With Ulcerative Colitis and Crohn Disease.

SIGNIFICANCE: Eosinophilic esophagitis (EoE) is an inflammatory condition characterized by T helper-2 (T H 2) cytokines. Ulcerative colitis (UC) and Crohn disease (CD) are inflammatory conditions with different clinical presentations and immune profiles. UC is associated with T H 2 cytokines and CD with T H 1 cytokines. We investigated potential differences in the association of EoE with UC and CD because of these different immune profiles. METHODS: We utilized ICD-9 and ICD-10 codes to find patients with inflammatory bowel disease (IBD) and EoE. We defined EoE as any esophageal biopsy with >15 eosinophils. We collected demographic, clinical, laboratory, endoscopic, and histological data. RESULTS: Thirty patients had both EoE and IBD. 14.9% of UC patients had EoE and 5.7% of CD patients had EoE. 64.7% of UC patients presented with UC and EoE at the same time, whereas 76.9% of CD patients presented with EoE at follow up. Ten of 13 CD patients were on anti-tumor necrosis factor (TNF) at EoE diagnosis. No UC patients were on anti-TNF at EoE diagnosis. Eighty-three percent of CD patients had mild disease or were in remission, whereas 50% of UC patients had moderate to severe disease at the time of EoE diagnosis. CONCLUSION: A higher percentage of UC than CD patients had EoE. EoE was more likely to be present at the initial diagnosis of UC than CD. EoE was more likely after diagnosis and treatment of CD with anti-TNF, when CD activity was mild or in remission. The difference in presentation suggests that anti-TNF or it's impact on inflammation may differentially impact the association of EoE with CD and UC.

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.

Upregulation of SNTB1 correlates with poor prognosis and promotes cell growth by negative regulating PKN2 in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most highly malignant tumors and has a complicated pathogenesis. A preliminary study identified syntrophin beta 1 (SNTB1) as a potential oncogene in CRC. However, the clinical significance, biological function, and underlying mechanisms of SNTB1 in CRC remain largely unknown. Thus, the present study aimed to investigate the role of SNTB1 in CRC. METHODS: The expression profile of SNTB1 in CRC samples was evaluated by database analysis, cDNA array, tissue microarray, quantitative real-time PCR (qPCR), and immunohistochemistry. SNTB1 expression in human CRC cells was silenced using short hairpin RNAs (shRNA)/small interfering RNAs (siRNA) and its mRNA and protein levels were assessed by qPCR and/or western blotting. Cell viability, survival, cell cycle, and apoptosis were determined by the CCK-8 assay, colony formation, and flow cytometry assays, respectively. A xenograft nude mouse model of CRC was established to validate the roles of SNTB1 in vivo. Immunohistochemistry and TUNEL staining were used to determine the expression of SNTB1, PCNA, and cell apoptosis in tissue samples. Isobaric tag for relative and absolute quantification (iTRAQ) was used to analyze the differentially expressed proteins after knockdown of SNTB1 in CRC cells. Silence of protein kinase N2 (PKN2) using si-PNK2 was performed for rescue experiments. RESULTS: SNTB1 expression was increased in CRC tissues compared with adjacent noncancerous tissues and the increased SNTB1 expression was associated with shorter overall survival of CRC patients. Silencing of SNTB1 suppressed cell viability and survival, induced cell cycle arrest and apoptosis in vitro, and inhibited the growth of CRC cells in vivo. Further elucidation of the regulation of STNB1 on CRC growth by iTRAQ analysis identified 210 up-regulated and 55 down-regulated proteins in CRC cells after SNTB knockdown. A PPI network analysis identified PKN2 as a hub protein and was up-regulated in CRC cells after SNTB1 knockdown. Western-blot analysis further confirmed that SNTB1 knockdown significantly up-regulated PKN2 protein expression in CRC cells and decreased the phosphorylation of both ERK1/2 and AKT. Moreover, rescue experiments indicated that PKN2 knockdown significantly rescued SNTB1 knockdown-mediated decrease in cell viability, survival, and increase of cell cycle arrest at G0/G1 phase and apoptosis of CRC cells. CONCLUSIONS: These findings indicate that SNTB1 is overexpressed in CRC. Elevated SNTB1 levels are correlated with shorter patient survival. Importantly, SNTB1 promotes tumor growth and progression of CRC, possibly by reducing the expression of PKN2 and activating the ERK and AKT signaling pathway. Our study highlights the potential of SNTB1 as a new prognostic factor and therapeutic target for CRC.

Acute Recurrent Pancreatitis in Children: A Study From the Pediatric Health Information System.

We investigated acute recurrent pancreatitis (ARP) in children using a national health care database. From 2002 to 2014, 26,435 children had a diagnosis of acute pancreatitis (AP); 10,648 discharges were index hospitalizations. A total of 6159 children had a single hospitalization for AP, whereas 4489 (42%) children underwent 15,787 rehospitalizations. Children experienced a median of 2 ARP-related hospitalizations with a median time between admissions of 86 days. Younger patients with a more severe index episode of AP were at a higher risk of ARP. ARP-related hospitalizations had an increased requirement for intensive care unit care compared with an index episode of AP.

Emergency Department Visits and Hospitalizations in Children With Chronic Pancreatitis in the United States.

We analyzed 2 national databases to assess the use of health care resources by children with chronic pancreatitis (CP). In 2012, the hospital discharge rate for pediatric CP was 2.73/100,000 children. Patients with CP were sicker with a greater burden of illness than age- and sex-matched counterparts. Acute pancreatitis occurred frequently in hospitalized children with CP. Abdominal pain and nausea, and vomiting were the most common gastrointestinal symptoms associated with emergency department visits in children with CP. A significant proportion of these visits resulted in a hospitalization. These findings add to our understanding of the epidemiology of CP in the United States.

Trends in endoscopic retrograde cholangiopancreatography in children within the United States, 2000-2009.

We investigated the volume of endoscopic retrograde cholangiopancreatographies (ERCPs) performed in hospitalized children in the United States using a nationwide healthcare administrative database for the years 2000 to 2009. A total of 22,153 cases of ERCP were identified: 6372 diagnostic and 17,314 therapeutic (1533 cases were recorded as undergoing both types during a single hospitalization). The number of ERCPs increased from 5337 to 6733 per year; diagnostic ERCPs decreased 43% and therapeutic increased 69% (significant decreasing trends for diagnostic and increasing for therapeutic ERCPs, P<0.001 for each analysis). Our results define a recent increase in the use of therapeutic ERCPs in hospitalized children.

Erratum: [Corrigendum] Pien Tze Huang inhibits hypoxia­induced epithelial­mesenchymal transition in human colon carcinoma cells through suppression of the HIF­1 pathway.

[This corrects the article DOI: 10.3892/etm.2014.1549.].

Pien Tze Huang Inhibits Proliferation of Colorectal Cancer Cells through Suppressing PNO1 Expression and Activating p53/p21 Signaling Pathway.

OBJECTIVE: To explore the regulatory effect of Pien Tze Huang (PZH) on targeting partner of NOB1 (PNO1) and it's down-stream mediators in colorectal cancer (CRC) cells. METHODS: Quantitative polymerase chain reaction was performed to determine mRNA levels of PNO1, TP53, and CDKN1A. Western blotting was performed to determine protein levels of PNO1, p53, and p21. HCT-8 cells were transduced with a lentivirus over-expressing PNO1. Colony formation assay was used to detect cell survival in PNO1 overexpression of HCT-8 cells after PZH treatment. Cell-cycle distribution, cell viability and cell apoptosis were performed to identify the effect of PNO1 overexpression on cell proliferation and apoptosis of HCT-8 cells after PZH treatment. Xenograft BALB/c nude mice bearing HCT116 cells transduced with sh-PNO1 or sh-Ctrl lentivirus were evaluated. Western blot assay was performed to detect PNO1, p53, p21 and PCNA expression in tumor sections. Terminal deoxynucleotidyl transferase dUTP nick end labling (TUNEL) assay was used to determine the apoptotic cells in tissues. RESULTS: PZH treatment decreased cell viability, down-regulated PNO1 expression, and up-regulated p53 and p21 expressions in HCT-8 cells (P<0.05). PNO1 overexpression attenuated the effects of PZH treatment, including the expression of p53 and p21, cell growth, cell viability, cell cycle arrest and cell apoptosis in vitro (P<0.05). PNO1 knockdown eliminated the effects of PZH treatment on tumor growth, inhibiting cell proliferation inhibition and apoptosis induction in vivo (P<0.05). Similarly, PNO1 knockdown attenuated the effects of PZH treatment on the down-regulation of PNO1 and up-regulation of p53 and p21 in vivo (P<0.05). CONCLUSION: The mechanism by which PZH induces its CRC anti-proliferative effect is at least in part by regulating the expression of PNO1 and its downstream targets p53 and p21.

Community-associated Clostridium difficile infection and antibiotics: a meta-analysis.

OBJECTIVES: Antibiotic exposure is the most important risk factor for Clostridium difficile infection (CDI). Most evaluations of antimicrobial risk factors have been conducted in healthcare settings. The objective of this meta-analysis was to evaluate the association between antibiotic exposure and community-associated CDI (CA-CDI) (i.e. symptom onset in the community with no healthcare facility admission within 12 weeks) and to determine the classes of antibiotics posing the greatest risk. METHODS: We searched four electronic databases for subject headings and text words related to CA-CDI and antibiotics. Studies that investigated the risk of CA-CDI associated with antibiotic usage were considered eligible. Data from the identified studies were combined using a random-effects model and ORs were calculated. RESULTS: Of 910 citations identified, eight studies (n = 30 184 patients) met our inclusion criteria. Antibiotic exposure was associated with an increased risk of CA-CDI (OR 6.91, 95% CI 4.17-11.44, I(2) = 95%). The risk was greatest with clindamycin (OR 20.43, 95% CI 8.50-49.09) followed by fluoroquinolones (OR 5.65, 95% CI 4.38-7.28), cephalosporins (OR 4.47, 95% CI 1.60-12.50), penicillins (OR 3.25, 95% CI 1.89-5.57), macrolides (OR 2.55, 95% CI 1.91-3.39) and sulphonamides/trimethoprim (OR 1.84, 95% CI 1.48-2.29). Tetracyclines were not associated with an increased CDI risk (OR 0.91, 95% CI 0.57-1.45). CONCLUSIONS: Antibiotic exposure was an important risk factor for CA-CDI, but the risk was different amongst different antibiotic classes. The risk was greatest with clindamycin followed by fluoroquinolones and cephalosporins, whereas tetracyclines were not associated with an increased risk.

Acid-suppressive therapy is associated with spontaneous bacterial peritonitis in cirrhotic patients: a meta-analysis.

BACKGROUND AND AIM: Proton pump inhibitors (PPI) and H(2) -receptor antagonists (H2RA) are frequently prescribed in hospitalized patients with cirrhosis. There are conflicting reports regarding the role of acid-suppressive therapy in predisposing hospitalized patients with cirrhosis to spontaneous bacterial peritonitis (SBP). The aim of this meta-analysis was to evaluate the association between acid-suppressive therapy and the risk of SBP in hospitalized patients with cirrhosis. METHODS: We searched MEDLINE and four other databases for subject headings and text words related to SBP and acid-suppressive therapy. All observational studies that investigated the risk of SBP associated with PPI/H2RA therapy and utilized SBP as an endpoint were considered eligible. Data from the identified studies were combined by means of a random-effects model and odds ratios (ORs) were calculated. RESULTS: Eight studies (n = 3815 patients) met inclusion criteria. The risk of hospitalized cirrhotic patients developing SBP increased when using acid-suppressive therapy. The risk was greater with PPI therapy (n = 3815; OR 3.15, 95% confidence interval 2.09-4.74) as compared to those on H2RA therapy (n = 562; OR 1.71, 95% confidence interval 0.97-3.01). CONCLUSIONS: Pharmacologic acid suppression was associated with a greater risk of SBP in hospitalized patients with cirrhosis. Cirrhotic patients receiving a PPI have approximately three times the risk of developing SBP compared with those not receiving this medication. Prospective studies may help clarify this relationship and shed light on the mechanism(s) by which acid-suppressive therapy increases the risk of SBP in hospitalized patients with cirrhosis.

T cell co-stimulatory molecules: a co-conspirator in the pathogenesis of eosinophilic esophagitis?

Eosinophilic esophagitis (EoE) has become a common gastrointestinal disease. It is characterized by severe eosinophil infiltration in the esophagus. EoE is strongly associated with food allergy, asthma, atopic dermatitis, and other allergic diseases. T lymphocytes, especially Th2 cells, play an instrumental role in the development of allergic inflammation. Recent studies have shown that the ligation of co-stimulatory molecules contributes to the activation, differentiation, and proliferation of T cells. In this review, we will discuss the growing evidence of co-stimulatory molecules including OX40, Light, and HVEM in the pathogenesis of Th2-driven EoE. Our goal is to provide the rationale for the development of novel therapy therapies that target co-stimulatory molecules.

A Case of Cyclic Vomiting Syndrome-Induced Hypertension Causing Posterior Reversible Encephalopathy Syndrome.

Cyclic vomiting syndrome (CVS) is characterized by repeated episodes of vomiting in a stereotyped pattern and is a known cause of hypertension. Our patient is a 10-year-old female who presented with nonbilious, nonbloody vomiting, and constipation concerning for a flare of her known CVS. During the hospital course, she developed intermittent severe hypertensive episodes, leading to an acute episode of altered mental status and a tonic-clonic seizure. Magnetic resonance imaging confirmed diagnosis of posterior reversible encephalopathy syndrome (PRES) after eliminating other organic etiologies. This is one of the first documented cases of CVS-induced hypertension causing PRES.

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.