Left Main Coronary Artery to Superior Vena Cava Fistula Unmasked by Endarteritis.

Coronary artery fistulas are rare vascular malformations that can present with a broad range of symptoms. We present a case of a left main coronary artery to superior vena cava fistula that was discovered during a work-up for sepsis. A multidisciplinary approach is crucial for successful management of these vascular malformations. (Level of Difficulty: Beginner.).

Hypoplastic Coronary Artery Disease Presenting with Ventricular Fibrillation Cardiac Arrest.

Hypoplastic coronary artery disease is a rare congenital anomaly that may present with ischaemic heart disease, heart failure or sudden cardiac death (SCD). We describe a case of cardiac arrest in a healthy young man. Work-up revealed a hypoplastic left anterior descending artery. The patient underwent cardioverter-defibrillator implantation for secondary prevention. LEARNING POINTS: Hypoplastic coronary artery disease (HCAD) is a rare cause of cardiac arrest and should be suspected in cases of sudden cardiac death (SCD) in young adults.The mechanism in HCAD leading to ventricular fibrillation cardiac arrest is not well understood.Implantable cardioverter-defibrillator (ICD) implantation is recommended for secondary prevention of ventricular fibrillation.

Novel Associations Between Genome-Wide Single Nucleotide Polymorphisms and MR Enterography Features in Crohn's Disease Patients.

BACKGROUND: Patient genetic polymorphism is associated with Crohn's clinical behavior; however, its association with magnetic resonance enterography (MRE) imaging appearance is not known. PURPOSE: To analyze a set of known Crohn's disease (CD)-related single nucleotide polymorphisms for associations with MRE imaging phenotype and frequency of imaging. STUDY TYPE: Retrospective. POPULATION: 54 patients (mean age 40 years; 32 females and 22 males) with established CD from 2009 to 2016 who underwent baseline MRE and genetic testing for the presence of 168 single nucleotide polymorphisms (SNPs) potentially associated with inflammatory bowel disease. FIELD STRENGTH/SEQUENCE: 1.5T or 3T clinical scanners, standard MRE clinical pulse sequences, including T2 -weighted single-shot fast spin echo, balanced steady-state free precession, T2 -weighted fast spin echo fat-suppressed, and T1 -weighted fat-suppressed pre- and postcontrast imaging. ASSESSMENT: Three readers (all body imaging fellowship-trained radiologists) independently evaluated all imaging for the presence or absence of active disease and penetrating complications. Date of onset and frequency of endoscopies and cross-sectional imaging (CSI) were recorded. Disease behavior and distribution were categorized according to the Vienna and Montreal classifications, respectively. STATISTICAL TESTS: Student's t-test and Fisher's exact test were used to assess significance of continuous and categorical variables, respectively. A hidden Markov model statistical knockoff approach was also applied for the analysis of genetic-imaging associations, with corrected P < 0.05 considered significant. RESULTS: MRE demonstrated active bowel inflammation in 42 (78%) patients, strictures in 13 (28%), and fistulae in 13 (28%). The SNP rs1292053 (RBS6KB1) was highly associated with small bowel inflammation and luminal narrowing, with observed frequencies of association 0.66 and 0.39, respectively (P = 0.001). rs6062504 (Decoy receptor 3) was associated with lower age of onset (P = 0.012), higher proportion of early disease onset patients (P = 0.012), and higher average number of CSI/year (P = 0.014). DATA CONCLUSION: This study demonstrated significant associations between CD genotype and MRE phenotype and frequency of cross-sectional imaging. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Rare Case of Coincident Quadricuspid Pulmonic Valve and Suprapulmonic Ridge: Multimodality Imaging.

A 32-year-old woman with a history of mild congenital pulmonic stenosis presented with new dyspnea on exertion. Multimodal imaging revealed a quadricuspid pulmonic valve with supravalvular ridge. We illustrate the evaluation and diagnosis of this rare condition. (Level of Difficulty: Advanced.).

Postoperative atrial fibrillation is associated with increased morbidity and resource utilization after left ventricular assist device placement.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a known risk factor for morbidity and mortality after cardiac surgery but has not been investigated in the left ventricular assist device (LVAD) population. We hypothesize that POAF will increase morbidity and resource utilization after LVAD placement. METHODS: Records were extracted for all patients in a regional database who underwent continuous-flow LVAD placement (n = 1064, 2009-2017). Patients without a history of atrial fibrillation (n = 689) were stratified by POAF for univariate analysis. Multivariable regression models calculated the risk-adjusted association of arrhythmias on outcomes and resource utilization. RESULTS: The incidence of new-onset POAF was 17.6%, and patients who developed POAF were older and more likely to have moderate/severe mitral regurgitation, a history of stroke, and concomitant tricuspid surgery. After risk adjustment, POAF was not associated with operative mortality or stroke but was associated with major morbidity (odds ratio [OR] 2.5 P = .0004), prolonged ventilation (OR 2.7, P < .0001), unplanned right ventricular assist device (OR 2.9, P = .01), and a trend toward renal failure (OR 2.0, P = .06). In addition, POAF was associated with greater risk-adjusted resource utilization, including discharge to a facility (OR 2.2, P = .007), an additional 4.9 postoperative days (P = .02), and 88 hours in the intensive care unit (P = .01). CONCLUSIONS: POAF was associated with increased major morbidity, possibly from worsening right heart failure leading to increased renal failure and unplanned right ventricular assist device placement. This led to patients with POAF having longer intensive care unit and hospital stays and more frequent discharges to a facility.

Ontology-based collection, representation and analysis of drug-associated neuropathy adverse events.

BACKGROUND: Neuropathy often occurs following drug treatment such as chemotherapy. Severe instances of neuropathy can result in cessation of life-saving chemotherapy treatment. RESULTS: To support data representation and analysis of drug-associated neuropathy adverse events (AEs), we developed the Ontology of Drug Neuropathy Adverse Events (ODNAE). ODNAE extends the Ontology of Adverse Events (OAE). Our combinatorial approach identified 215 US FDA-licensed small molecule drugs that induce signs and symptoms of various types of neuropathy. ODNAE imports related drugs from the Drug Ontology (DrON) with their chemical ingredients defined in ChEBI. ODNAE includes 139 drug mechanisms of action from NDF-RT and 186 biological processes represented in the Gene Ontology (GO). In total ODNAE contains 1579 terms. Our analysis of the ODNAE knowledge base shows neuropathy-inducing drugs classified under specific molecular entity groups, especially carbon, pnictogen, chalcogen, and heterocyclic compounds. The carbon drug group includes 127 organic chemical drugs. Thirty nine receptor agonist and antagonist terms were identified, including 4 pairs (31 drugs) of agonists and antagonists that share targets (e.g., adrenergic receptor, dopamine, serotonin, and sex hormone receptor). Many drugs regulate neurological system processes (e.g., negative regulation of dopamine or serotonin uptake). SPARQL scripts were used to query the ODNAE ontology knowledge base. CONCLUSIONS: ODNAE is an effective platform for building a drug-induced neuropathy knowledge base and for analyzing the underlying mechanisms of drug-induced neuropathy. The ODNAE-based methods used in this study can also be extended to the representation and study of other categories of adverse events.

High C-Reactive Protein Is Associated with Poor Sleep Quality Independent of Nocturnal Symptoms in Patients with Inflammatory Bowel Disease.

BACKGROUND: Sleep disruption is common in inflammatory bowel diseases (IBD). However, studies demonstrating a similar prevalence in irritable bowel syndrome suggest that nighttime disruption due to diarrhea and abdominal pain may be key drivers of poor sleep quality. Whether inflammation is associated with poor sleep independently has not been examined previously. METHODS: This single-center study included subjects with IBD recruited to an ongoing prospective registry who completed a questionnaire assessing sleep quality and mood. Inflammatory marker levels [C-reactive protein (CRP), erythrocyte sedimentation rate] and clinical disease activity including nighttime disruption on the day of enrollment were obtained from the medical record. Logistic regression models were used to identify predictors of sleep quality. RESULTS: The study included 131 subjects (72 women) with a median age of IBD diagnosis of 25 years. Twenty-three subjects (19 %) had a high C-reactive protein level (≥8 mg/dL). Poor sleep was more common in those with high CRP levels than with normal values (70 vs. 39 %, p = 0.009). This association remained significant on multivariate analysis [Odds ratio (OR) 4.12, 95 % confidence interval (CI) 1.38-12.29]. Adjusting for the presence of nighttime disruption did not significant alter this association (OR 3.16, 95 % CI 1.01-9.90). High CRP correlated with poor sleep even in patients not experiencing nocturnal symptoms (n = 101, OR 4.89, 95 % CI 1.24-19.36). CONCLUSION: High CRP is associated with poor sleep quality in IBD independent of the presence of nighttime disruptions, suggesting that a relationship exists between circulating inflammatory markers and sleep.

Early life environment and natural history of inflammatory bowel diseases.

BACKGROUND: Early life exposures may modify risk of inflammatory bowel diseases (IBD; Crohn's disease (CD), ulcerative colitis (UC)). However, the relationship between early life exposures and natural history of IBD has not been previously examined. METHODS: This single center study included patients with CD or UC recruited in a prospective IBD registry. Enrolled patients completed a detailed environmental questionnaire that assessed various early life environmental exposures. Our primary outcome was requirement for disease-related surgery in CD and UC. Logistic regression models defined independent effect of early life exposures, adjusting for potential confounders. RESULTS: Our study included 333 CD and 270 UC patients. Just over half were female with a median age at diagnosis of 25 years. One-third of the cohort had history of bowel surgery (31%) and nearly half had used at least one biologic agent (47%). Among those with CD, being breastfed was associated with reduced risk of CD-related surgery (34% vs. 55%), while childhood cigarette smoke exposure was associated with increased risk. On multivariate analysis, history of being breastfed (odds ratio (OR) 0.21, 95% confidence interval [CI] 0.09-0.46) and cigarette smoke exposure as a child (OR 2.17, 95% CI 1.10-4.29) remained independently associated with surgery. None of the early life variables influenced disease phenotype or outcome in UC. CONCLUSION: A history of being breastfed was associated with a decreased risk while childhood cigarette smoke exposure was associated with an increased risk of surgery in patients with CD. Further investigation to examine biological mechanisms is warranted.

OAE: The Ontology of Adverse Events.

BACKGROUND: A medical intervention is a medical procedure or application intended to relieve or prevent illness or injury. Examples of medical interventions include vaccination and drug administration. After a medical intervention, adverse events (AEs) may occur which lie outside the intended consequences of the intervention. The representation and analysis of AEs are critical to the improvement of public health. DESCRIPTION: The Ontology of Adverse Events (OAE), previously named Adverse Event Ontology (AEO), is a community-driven ontology developed to standardize and integrate data relating to AEs arising subsequent to medical interventions, as well as to support computer-assisted reasoning. OAE has over 3,000 terms with unique identifiers, including terms imported from existing ontologies and more than 1,800 OAE-specific terms. In OAE, the term 'adverse event' denotes a pathological bodily process in a patient that occurs after a medical intervention. Causal adverse events are defined by OAE as those events that are causal consequences of a medical intervention. OAE represents various adverse events based on patient anatomic regions and clinical outcomes, including symptoms, signs, and abnormal processes. OAE has been used in the analysis of several different sorts of vaccine and drug adverse event data. For example, using the data extracted from the Vaccine Adverse Event Reporting System (VAERS), OAE was used to analyse vaccine adverse events associated with the administrations of different types of influenza vaccines. OAE has also been used to represent and classify the vaccine adverse events cited in package inserts of FDA-licensed human vaccines in the USA. CONCLUSION: OAE is a biomedical ontology that logically defines and classifies various adverse events occurring after medical interventions. OAE has successfully been applied in several adverse event studies. The OAE ontological framework provides a platform for systematic representation and analysis of adverse events and of the factors (e.g., vaccinee age) important for determining their clinical outcomes.

Mu-opioid signaling modulates biphasic expression of TrkB and IκBα genes and neurite outgrowth in differentiating and differentiated human neuroblastoma cells.

Chronic opioid exposure leads to changes in gene expression (functional changes), resulting in structural changes in neural circuits that are linked to eventually behavioral changes. Little is known about the cellular and molecular mechanisms of how such changes occur. In this study, we found that mu-opioid [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin (DAMGO) and morphine exposure led to dynamic changes in neural differentiation- and growth-associated genes, IκBα and NTRK2 (TrkB), in differentiating and differentiated human neuroblastoma SH-SY5Y cells. Chromatin immunoprecipitation-polymerase chain reaction (ChIP-PCR) analysis revealed that binding of NF-κB/p65 to the IκBα promoter in living cells was temporally altered when the cells were exposed to morphine. The changes in gene expression correlated with the changes in neurite length of the RA-differentiating and RA-differentiated neuron-like cells. Our findings for the first time showed that TrkB signaling and NF-κB/IκBα signaling temporally correlated with each other in response to single-dose and repeated mu-opioid treatment in differentiating and differentiated human neuron-like cells. The findings from this human cell study in vitro indicate that both relatively high single-dose and chronic opioid exposure may induce the structural changes in the developing human brain and the adult brain by altering the expression of neuronal differentiation- and neurite outgrowth-related genes IκBa and TrkB in vivo.