Heterogeneity of asthma and the risk of celiac disease in children.

BACKGROUND: Although human leukocyte antigen (HLA)-DR and HLA-DQ genes and gluten play crucial roles in developing celiac disease (CD), most patients with these risk factors still do not develop CD, which indicates additional unrecognized risk factors. OBJECTIVE: To determine the association between asthma and the risk of CD in children. METHODS: We conducted a population-based retrospective case-control study in children who resided in Olmsted County, Minnesota. We identified children with CD (cases) between January 1, 1997, and December 31, 2014, and compared these with children without CD (controls) (1:2 matching). Asthma status was ascertained by using the predetermined asthma criteria (PAC) and the asthma predictive index (API). Data analysis included conditional logistic regression models and an unsupervised network analysis by using an independent phenome-wide association scan (PheWAS) data set. RESULTS: Although asthma status as determined by using PAC was not associated with the risk of CD (odds ratio [OR] 1.4 [95% confidence interval {CI}, 0.8-2.5]; p = 0.2), asthma status by using the API was significantly associated (OR 2.8 [95% CI, 1.3-6.0]; p = 0.008). A subgroup analysis indicated that children with both asthma as determined by using PAC and a family history of asthma had an increased risk of CD compared with those without asthma (OR 2.28 [95% CI, 1.11-4.67]; p = 0.024). PheWAS data showed a cluster of asthma single nucleotide polymorphisms and patients with CD. CONCLUSION: A subgroup of children with asthma who also had a family history of asthma seemed to be at an increased risk of CD, and, thus, the third factor that underlies the risk of CD might be related to genetic factors for asthma. Heterogeneity of asthma plays a role in determining the risk of asthma-related comorbidity.

Characterization of Admission Types in Medically Hospitalized Patients Prescribed Clozapine.

BACKGROUND: Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia; however, rigorous monitoring is required to prevent or detect adverse drug events that contribute to morbidity and mortality. In addition to the Food and Drug Administration (FDA) boxed safety warnings specific to clozapine (agranulocytosis, hypotension, seizures, and cardiomyopathy/myocarditis), other adverse events such as pneumonia and gastrointestinal hypomotility have been reported in the literature to result in hospitalization. OBJECTIVE: To explore the reasons for medical hospitalization in patients prescribed clozapine, a retrospective chart review was completed. METHODS: Adults with schizophrenia or schizoaffective disorder prescribed clozapine were identified if they had a nonpsychiatric medical admission between 1/1/2003 and 8/1/2015. Demographics, admitting diagnosis, admitting service type, psychiatric consult information, clozapine dosing, and drug interactions were collected. RESULTS: Overall, 104 patients, representing 248 hospitalizations, were admitted to a medical unit during the study period. The predominant admission types were for the management of either pulmonary (32.2%) or gastrointestinal (19.8%) illnesses. The most common pulmonary diagnosis was pneumonia, accounting for 58% of pulmonary admissions. Further, 61.2% of the gastrointestinal admissions were related to hypomotility, ranging from constipation to death. Clozapine was discontinued owing to neutropenia in 2 patients; however, in both cases concomitant chemotherapy had been given. CONCLUSION: In patients prescribed clozapine admitted to nonpsychiatric medical settings, gastrointestinal and pulmonary illnesses were common, but not illnesses related to boxed warnings. Additional research is needed to better assess the causality and true incidence of gastrointestinal or pulmonary events associated with clozapine. Furthermore, clinicians must be prepared to prevent, detect, and manage potentially life-threatening events associated with clozapine.

Pheochromocytoma with Synchronous Ipsilateral Adrenal Cortical Adenoma.

BACKGROUND: Pheochromocytoma with synchronous ipsilateral adrenal cortical adenoma (PSCA) may present with mixed clinical, biochemical, and radiological features characteristic to each neoplasm subtype. METHODS: All patients with a pathological diagnosis of pheochromocytoma were evaluated for an ipsilateral cortical adenoma from 1994 through 2015. Retrospectively extracted data included indications for adrenalectomy, diagnostic workup (biochemical and radiographic), operative characteristics, pathological findings, and postoperative complications. RESULTS: Sixteen of 413 patients (4%) undergoing adrenalectomy for pheochromocytoma had a PSCA. Median patient age was 57.7 years (IQR 50.1, 63.1); 50% were male. On imaging, 75% of the adrenal neoplasms were found incidentally and only 50% were reported to have a synchronous ipsilateral neoplasm based on imaging findings. Clinically important cortical hormone secretion was diagnosed in 38% of these patients; 25% had glucocorticoid secretory autonomy; and 13% had primary aldosteronism. CONCLUSION: Physicians should be aware that adrenal neoplasms with mixed diagnostic findings may represent PSCA. Evaluation should be performed on this co-occurrence to prevent perioperative complications from resection of an unexpected secretory cortical neoplasm.

An Immunocompromised Child with Bloodstream Infection Caused by Two Escherichia coli Strains, One Harboring NDM-5 and the Other Harboring OXA-48-Like Carbapenemase.

We describe a 16-year-old neutropenic patient from the Middle East with bloodstream infection caused by two carbapenemase-producing Escherichia coli isolates that we characterized by whole-genome sequencing. While one displayed meropenem resistance and was blaNDM positive, the other demonstrated meropenem susceptibility yet harbored blaOXA181 (which encodes a blaOXA48-like enzyme). This report highlights the challenge of laboratory detection of blaOXA48-like enzymes and the clinical implications of genotypic resistance detection in carbapenemase-producing Enterobacteriaceae.

Asthma and Risk of Appendicitis in Children: A Population-Based Case-Control Study.

OBJECTIVE: To assess whether asthma is associated with risk of appendicitis in children. METHODS: We used a population-based case-control study design using a comprehensive medical record review and predetermined criteria for appendicitis and asthma. All children (age younger than 18 years of age) who resided in Olmsted County, Minnesota, and developed appendicitis between 2006 and 2012 were matched to controls (1:1) with regard to birthday, gender, registration date, and index date. Asthma status was ascertained using predetermined criteria. Active (current) asthma was defined as the presence of asthma symptoms or asthma-related events (eg, medication use, clinic visits, emergency department, or hospitalization) within 1 year before the index date. Inactive asthma was defined as subjects without these events. A conditional logistic regression model was used. RESULTS: Among the 309 appendicitis cases identified, when stratified according to asthma status, active asthma was associated with significantly increased risk of appendicitis compared with inactive asthma (odds ratio [OR] = 2.48; 95% confidence interval [CI], 1.22-5.03) and to no asthma (OR = 1.88; 95% CI, 1.07-3.27; overall P = .035). When controlling for potential confounders such as gender, age, and smoking status, active asthma was associated with a higher odds of developing appendicitis compared with nonasthmatic patients (adjusted OR = 1.75; 95% CI, 0.99-3.11) whereas inactive asthma was not (overall P = .049). Tobacco smoke exposure within 3 months was associated with an increased risk of appendicitis (adjusted OR = 1.66; 95% CI, 1.02-2.69). Among asthma medications, leukotriene receptor antagonists reduced the risk of appendicitis (OR = 0.18; 95% CI, 0.04-0.74). CONCLUSIONS: Active asthma might be an unrecognized risk factor for appendicitis in children whereas a history of inactive asthma does not pose such risk. Further investigation exploring the underlying mechanisms is warranted.