Risk factors for recurrent emergency care utilization for flares in inflammatory bowel disease.

OBJECTIVES: Patients with inflammatory bowel disease (IBD) need frequent emergency care due to flares of their disease. However, understanding which patients are most vulnerable to repeat emergency care due to recurrent flares of their disease remains poor. METHODS: This was a retrospective cohort study of Kaiser Permanente Northern California health plan members aged ≥18 years between 2009 and 2018. Our primary outcome was occurrence of repeat emergency department (ED) visits with a primary diagnosis code of IBD in the 6 months following their index ED visit. Baseline characteristics and clinical service use patterns were extracted. We used multivariable negative binomial regression analysis to measure the incident risk of a recurrent ED visit within 6 months. RESULTS: We found 2111 patients who met eligibility criteria, of whom 56.7% were female and 39.7% were non-White. During the 6-month observation period, 19.3% (n = 408) returned to the ED for a second IBD flare. In adjusted analyses, we found older age (incident risk ratio [IRR] 0.44, 95% confidence interval [CI] 0.31-0.62 for age 60+ compared to 18-30), higher neighborhood household income (IRR 0.80, 95% CI 0.65-0.98 for income ≥$85,000), and diagnosis of alcohol use disorder were associated with a lower risk of repeat ED utilization (IRR 0.62, 95% CI 0.41-0.93), while presence of mood disorder (IRR 1.26, 95% CI 1.03-1.58), history of opiate prescription (IRR 1.38, 95% CI 1.10-1.73), and corticosteroid prescription (IRR 1.57, 95% CI 1.27-1.95) were associated with increased risk of repeat ED utilization. Prompt outpatient follow-up was not associated with a lower odds of recurrent ED utilization (IRR 0.93, 95% CI 0.75-1.15). CONCLUSIONS: Our study identified multiple patient characteristics associated with higher recurrent short-term use of the ED for IBD care. Although we did not find prompt outpatient follow-up after initial ED visit to be protective, targeted interventions directed at high-risk individuals based on mood disorders, opiate use, or steroid use may help to optimize care and health care utilization.

Psychiatric Diagnoses, Medication, and Service Use Among Patients Who Receive Emergency Care for Inflammatory Bowel Diseases.

This study examined relative psychiatric burden among patients who presented to the emergency department once or more than once for inflammatory bowel disease visits. Results highlight the need for integration of psychiatric and gastrointestinal care among high-risk inflammatory bowel disease patients.

Using Search Engine Query Data to Explore the Epidemiology of Common Gastrointestinal Symptoms.

BACKGROUND: Internet searches are an increasingly used tool in medical research. To date, no studies have examined Google search data in relation to common gastrointestinal symptoms. AIMS: The aim of this study was to compare trends in Internet search volume with clinical datasets for common gastrointestinal symptoms. METHODS: Using Google Trends, we recorded relative changes in volume of searches related to dysphagia, vomiting, and diarrhea in the USA between January 2008 and January 2011. We queried the National Inpatient Sample (NIS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS) during this time period and identified cases related to these symptoms. We assessed the correlation between Google Trends and these two clinical datasets, as well as examined seasonal variation trends. RESULTS: Changes to Google search volume for all three symptoms correlated significantly with changes to NIS output (dysphagia: r = 0.5, P = 0.002; diarrhea: r = 0.79, P < 0.001; vomiting: r = 0.76, P < 0.001). Both Google and NIS data showed that the prevalence of all three symptoms rose during the time period studied. On the other hand, the NHAMCS data trends during this time period did not correlate well with either the NIS or the Google data for any of the three symptoms studied. Both the NIS and Google data showed modest seasonal variation. CONCLUSIONS: Changes to the population burden of chronic GI symptoms may be tracked by monitoring changes to Google search engine query volume over time. These data demonstrate that the prevalence of common GI symptoms is rising over time.

Absence of pancreatic intraepithelial neoplasia predicts poor survival after resection of pancreatic cancer.

OBJECTIVES: Pancreatic intraepithelial neoplasia (PanIN), thought to represent the dominant precursor of pancreatic adenocarcinoma (PDAC), is often found synchronously adjacent to resected PDAC tumors. However, its prognostic significance on outcome after PDAC resection is unknown. METHODS: A total of 342 patients who underwent resection for PDAC between 2005 and 2010 at a single institution were identified and stratified according to highest grade of PanIN demonstrated surrounding the tumor. Clinical and pathologic characteristics of each patient and tissue were recorded and analyzed. The primary outcome was length of survival after resection. RESULTS: An absence of PanIN lesions was identified in 32 patients (9%), low grade PanIN without synchronous high grade lesions was identified in 52 patients (15%), and high grade PanIN was found in 258 patients (75%). Median survival were 12.8 months for the non-PanIN group, 26.3 months for the low-grade PanIN group, and 23.8 months for the high-grade PanIN groups (P = 0.043). In multivariable analysis, absence of PanIN was independently associated with poor survival (P = 0.002). CONCLUSIONS: The patients who demonstrate an absence of PanIN in the pancreatic tissue adjacent to the resected PDAC tumor have shorter postresection survival compared with those who demonstrate a PanIN lesion.

Celiac disease in normal-weight and overweight children: clinical features and growth outcomes following a gluten-free diet.

OBJECTIVES: There are few data on pediatric celiac disease in the United States. The aim of our study was to describe the presentation of celiac disease among children with a normal and an elevated body mass index (BMI) for age, and to study their BMI changes following a gluten-free diet (GFD). PATIENTS AND METHODS: One hundred forty-two children (age 13 months-19 years) with biopsy-proven celiac disease, contained in a registry of patients studied at our center from 2000 to 2008, had follow-up growth data available. Patients' height, weight, and BMI were converted to z scores for age and grouped by BMI as underweight, normal, and overweight. Compliance was confirmed using results of serological assays, and data of noncompliant patients were analyzed separately. Data were analyzed during the observation period and were expressed as change in height, weight, and BMI z score per month of dietary treatment. RESULTS: Nearly 19% of patients had an elevated BMI at diagnosis (12.6% overweight, 6% obese) and 74.5% presented with a normal BMI. The mean duration of follow-up was 35.6 months. Seventy-five percent of patients with an elevated BMI at diagnosis decreased their BMI z scores significantly after adherence to a GFD, normalizing it in 44% of cases. Of patients with a normal BMI at diagnosis, weight z scores increased significantly after treatment, and 13% became overweight. CONCLUSIONS: Both normal weight and overweight frequently occur in North American children presenting with celiac disease. A GFD may have a beneficial effect upon the BMI of overweight and obese children with celiac disease.

C3a receptor antagonist attenuates brain injury after intracerebral hemorrhage.

Neuroprotective therapy targeting the complement cascade may reduce injury associated with intracerebral hemorrhage (ICH). We investigated the role of C3a-receptor antagonist (C3aRA) after ICH in mice. Autologous whole blood was infused into the right striatum of mice that were treated with C3aRA or vehicle, using both a pre- and postinjury dosing regimen. Hematoma volume, brain water content, and inflammatory cell profile were assessed at 72 h post-ICH. Neurologic dysfunction was assessed by evaluating both spatial memory and sensorimotor capacity. Animals pretreated with C3aRA showed significantly improved neurologic function, brain water content, and granulocyte infiltration relative to vehicle-treated animals when assessed at 72 h. There was no significant difference in hemorrhagic/nonhemorrhagic ratio of microglial activation among all groups. Hematoma volumes were also not significantly different between C3aRA-treated and vehicle-treated animals. Administration of C3aRA beginning 6 h postinjury afforded significant amelioration of neurologic dysfunction as well as a reduction in brain water content. Treatment with C3aRA improved neurologic outcome while reducing inflammatory cell infiltration and brain edema formation after experimental ICH in mice. Results of this study suggest that the C3a receptor may be a promising target for therapeutic intervention in hemorrhagic stroke.

Neuronal RAGE expression modulates severity of injury following transient focal cerebral ischemia.

Inflammation has a significant role in the neurological injury that follows stroke. The receptor for advanced-glycation end products (RAGE) is a multiligand member of the immunoglobulin superfamily that has been implicated in multiple neuronal and inflammatory stress processes. To directly test the role of neuronal RAGE in stroke, we employed two cohorts of transgenic mice, one over-expressing full-length functional human RAGE in neurons, and the other a human RAGE transgene in which deletion of the cytoplasmic domain of the receptor in neurons suppresses signal transduction stimulated by ligands (referred to as dominant negative or DN-RAGE). We found a statistically significant increase in stroke volume in the RAGE over-expressing cohort compared to normal controls, and a trend towards decreased stroke volume in the DN RAGE cohort. These results indicate that RAGE signaling directly contributes to pathology in cerebral ischemia.

C3a receptor modulation of granulocyte infiltration after murine focal cerebral ischemia is reperfusion dependent.

The complement anaphylatoxin C3a contributes to injury after cerebral ischemia in mice. This study assesses the effect of C3a receptor antagonist (C3aRA) on leukocyte infiltration into the ischemic zone. Transient or permanent middle cerebral artery occlusion (MCAO) was induced in wild-type C57Bl/6 mice. Intraperitoneal C3aRA or vehicle was administered 45 mins before or 1 h after occlusion. Twenty-four hours after occlusion, we harvested brain tissue and purified inflammatory cells using flow cytometry. Soluble intercellular adhesion molecule (ICAM)-1 protein levels were assessed using enzyme-linked immunosorbent assays, and ICAM-1 and C3a receptor (C3aR) expression was confirmed via immunohistochemistry. In the transient MCAO model, animals receiving C3aRA showed smaller strokes, less upregulation of C3aR-positive granulocytes, and less ICAM-1 protein on endothelial cells than vehicle-treated animals; no significant differences in other inflammatory cell populations were observed. C3a receptor antagonist-treated and vehicle-treated animals showed no differences in stroke volume or inflammatory cell populations after permanent MCAO. These data suggest that blocking the binding of C3a to C3aR modulates tissue injury in reperfused stroke by inhibiting the recruitment of neutrophils to the ischemic zone. It further establishes antagonism of the C3a anaphylatoxin as a promising strategy for ameliorating injury after ischemia/reperfusion.

Complement component C3 mediates inflammatory injury following focal cerebral ischemia.

The complement cascade has been implicated in ischemia/reperfusion injury, and recent studies have shown that complement inhibition is a promising treatment option for acute stroke. The development of clinically useful therapies has been hindered, however, by insufficient understanding of which complement subcomponents contribute to post-ischemic injury. To address this issue, we subjected mice deficient in selected complement proteins (C1q, C3, C5) to transient focal cerebral ischemia. Of the strains investigated, only C3-/- mice were protected, as demonstrated by 34% reductions in both infarct volume (P<0.01) and neurological deficit score (P<0.05). C3-deficient mice also manifested decreased granulocyte infiltration (P<0.02) and reduced oxidative stress (P<0.05). Finally, administration of a C3a-receptor antagonist resulted in commensurate neurological improvement and stroke volume reduction (P<0.05). Together, these results establish C3 activation as the key constituent in complement-related inflammatory tissue injury following stroke and suggest a C3a anaphylatoxin-mediated mechanism.

Temporal pattern of C1q deposition after transient focal cerebral ischemia.

Recent studies have focused on elucidating the contribution of individual complement proteins to post-ischemic cellular injury. As the timing of complement activation and deposition after cerebral ischemia is not well understood, our study investigates the temporal pattern of C1q accumulation after experimental murine stroke. Brains were harvested from mice subjected to transient focal cerebral ischemia at 3, 6, 12, and 24 hr post reperfusion. Western blotting and light microscopy were employed to determine the temporal course of C1q protein accumulation and correlate this sequence with infarct evolution observed with TTC staining. Confocal microscopy was utilized to further characterize the cellular localization and characteristics of C1q deposition. Western Blot analysis showed that C1q protein begins to accumulate in the ischemic hemisphere between 3 and 6 hr post-ischemia. Light microscopy confirmed these findings, showing concurrent C1q protein staining of neurons. Confocal microscopy demonstrated co-localization of C1q protein with neuronal cell bodies as well as necrotic cellular debris. These experiments demonstrate the accumulation of C1q protein on neurons during the period of greatest infarct evolution. This data provides information regarding the optimal time window during which a potentially neuroprotective anti-C1q strategy is most likely to achieve therapeutic success.