Associations between the size and location of myocardial infarction and cerebral infarction.

BACKGROUND: Myocardial infarction (MI) is a known cause of cerebral infarction. We assessed whether the size and location of MI is associated with the risk of cerebral infarction. METHODS AND RESULTS: We performed a cross-sectional study of adults who underwent both brain MRI and delayed-enhancement cardiac MRI (DE-CMR) within 365 days of each other at Weill Cornell Medicine between 2014 and 2017 and had evidence of MI on DE-CMR. We used multiple logistic regression to evaluate associations between MI size and any cerebral infarction, apical MI location and any cerebral infarction, and MI size/location and cortical versus subcortical cerebral infarction. Models were adjusted for demographics, and the total number of vascular risk factors. Among 234 patients who underwent both DE-CMR and brain MRI within 365 days, 76 had evidence for MI on DE-CMR. Among these 76 patients, 51 (67.1%) had evidence of cerebral infarction. The size of MI (global MI burden) was not associated with any cerebral infarction (OR per 5% increase in MI size, 1.12; 95% CI, 0.85-1.47), but was associated with cortical cerebral infarction (OR per 5% increase in MI size, 1.30; 95% CI, 1.00.-1.68). Similarly, apical MI location was not associated with any cerebral infarction (OR 2.63, 95% CI, 0.78-8.87), but was associated with cortical cerebral infarction (OR, 3.67; 95% CI, 1.19-11.33). CONCLUSION: Among patients with MI on cardiac MRI, both size and apical location of MI were associated with cortical cerebral infarction. Our results may help stratify cardioembolic risk and inform antithrombotic treatment algorithms among patients with MI.

Stroke Risk Following Takotsubo Cardiomyopathy.

BACKGROUND AND PURPOSE: Takotsubo cardiomyopathy, also known as stress cardiomyopathy, is an increasingly recognized cause of left ventricular dysfunction. Previously considered a benign disease, Takotsubo cardiomyopathy may be a risk factor of ischemic stroke based on recent small, single-center case series. The strength and temporal profile of this association remains uncertain. METHODS: We performed a cohort-crossover study using administrative claims data on all emergency department visits and acute care hospitalizations from 2005 to 2015 in California, New York, and Florida. We identified patients with Takotsubo cardiomyopathy, excluding those with a prior or concomitant stroke diagnosis. We compared the risk of ischemic stroke in the first year after Takotsubo cardiomyopathy to the risk of ischemic stroke in the second year after Takotsubo cardiomyopathy. Takotsubo cardiomyopathy and ischemic stroke were ascertained using previously validated ICD-9-CM codes. Absolute risks and odds ratios (OR) were calculated using McNemar test for matched data. RESULTS: Among 5283 patients with Takotsubo cardiomyopathy (mean age, 67 years; 92% female), we identified 49 ischemic strokes during the first year after Takotsubo cardiomyopathy versus 19 ischemic strokes during the second year after. The risk of stroke was significantly higher in the year after Takotsubo cardiomyopathy (absolute increase, 0.6%; 95% CI: 0.2-0.9; OR: 2.6; 95% CI: 1.5-4.6) as compared to the control period. CONCLUSION: We found a heightened risk of ischemic stroke in the year after a diagnosis of Takotsubo cardiomyopathy, although the absolute risk increase was small.

Tricuspid Stenosis in Pregnancy: A Valve-in-Valve Conundrum.

Redo tricuspid valve replacement has high surgical operative mortality. Transcatheter valve-in-valve provides a viable option for valve replacement. We discuss the decision-making process involved in performing transcatheter tricuspid valve-in-valve replacement in a 23-week pregnant woman with multiple comorbidities and symptomatic severe bioprosthetic stenosis. (Level of Difficulty: Intermediate.).

Survivin in Insulin-Like Growth Factor-Induced Resistance to Lapatinib in Head and Neck Squamous Carcinoma Cells.

Epidermal growth factor receptor (EGFR) inhibitors have limited efficacy in head and neck squamous cell carcinoma (HNSCC) due to various resistance mechanisms, such as activation of the insulin-like growth factor-1 receptor (IGF1R), which initiates pro-survival signaling. Survivin, a member of the inhibitor of apoptosis proteins family, is expressed at relatively high levels in malignant tissues and plays a role in cell division. Expression of survivin in tumors has been shown to correlate with poor prognosis due to chemotherapy resistance and anti-apoptotic behavior. We previously demonstrated that activation of the IGF1R reduces sensitivity to EGFR-tyrosine kinase inhibitors (TKIs) via reduced apoptosis suggesting a role of survivin in this process. This study evaluates the role of survivin in IGF1R-mediated lapatinib resistance. Using HNSCC cell lines FaDu and SCC25, survivin expression increased and lapatinib sensitivity decreased with IGF1R activation. Further, these effects were reversed by the survivin inhibitor YM-155. Conversely, survivin expression and lapatinib sensitivity were unchanged with IGF1R activation in UNC10 cells. YM-155 enhanced the inhibitory effect of lapatinib on UNC10 cells, regardless of activation of the IGF1R. These results demonstrate that enhanced survivin expression correlates with IGF1R-mediated lapatinib resistance in HNSCC cells and suggest that regulation of survivin expression may be a key mechanistic element in IGF1R-based therapeutic resistance. Combinatorial treatment with survivin antagonists and EGFR-TKIs warrants further investigation.

The Risk of Takotsubo Cardiomyopathy in Acute Neurological Disease.

BACKGROUND: Case series have reported reversible left ventricular dysfunction, also known as stress cardiomyopathy or Takotsubo cardiomyopathy (TCM), in the setting of acute neurological diseases such as subarachnoid hemorrhage. The relative associations between various neurological diseases and Takotsubo remain incompletely understood. METHODS: We performed a cross-sectional study of all adults in the National Inpatient Sample, a nationally representative sample of US hospitalizations, from 2006 to 2014. Our exposures of interest were primary diagnoses of acute neurological disease, defined by ICD-9-CM diagnosis codes. Our outcome was a diagnosis of TCM. Binary logistic regression models were used to examine the associations between our pre-specified neurological diagnoses and TCM after adjustment for demographics. RESULTS: Among acute neurological diagnoses, the strongest associations were seen with subarachnoid hemorrhage (odds ratio [OR] 11.7; 95% confidence interval [CI] 10.2-13.4), status epilepticus (OR 4.9; 95% CI 3.7-6.3), and seizures (OR 1.3; 95% CI 1.1-1.5). In a sensitivity analysis including secondary diagnoses of acute neurological diagnoses, associations were also seen with transient global amnesia (OR 2.3; 95% CI 1.5-3.6), meningoencephalitis (OR 2.1; 95% CI 1.7-2.5), migraine (OR 1.7; 95% CI 1.5-1.8), intracerebral hemorrhage (OR 1.3; 95% CI 1.1-1.5), and ischemic stroke (OR 1.2; 95% CI 1.1-1.3). In addition, female sex was strongly associated with Takotsubo (OR 5.1; 95% CI 4.9-5.4). CONCLUSION: TCM appears to be associated with varying degrees with several acute neurological diseases besides subarachnoid hemorrhage.

Thirty-Day Readmission Rates, Timing, Causes, and Costs after ST-Segment-Elevation Myocardial Infarction in the United States: A National Readmission Database Analysis 2010-2014.

Background Readmission after ST-segment-elevation myocardial infarction ( STEMI ) poses an enormous economic burden to the US healthcare system. Efforts to prevent readmissions should be based on understanding the timing and causes of these readmissions. This study aimed to investigate contemporary causes, timing, and cost of 30-day readmissions after STEMI . Methods and Results All STEMI hospitalizations were selected in the Nationwide Readmissions Database ( NRD ) from 2010 to 2014. The 30-day readmission rate as well as the primary cause and cost of readmission were examined. Multivariate regression analysis was performed to identify the predictors of 30-day readmission and increased cumulative cost. From 2010 to 2014, the 30-day readmission rate after STEMI was 12.3%. Within 7 days of discharge, 43.9% were readmitted, and 67.3% were readmitted within 14 days. The annual rate of 30-day readmission decreased by 19% from 2010 to 2014 ( P<0.001). Female sex, AIDS , anemia, chronic kidney disease , collagen vascular disease, diabetes mellitus, hypertension, pulmonary hypertension, congestive heart failure , atrial fibrillation, and increased length of stay were independent predictors of 30-day readmission. A large proportion of patients (41.6%) were readmitted for noncardiac reasons. After multivariate adjustment, 30-day readmission was associated with a 47.9% increase in cumulative cost ( P<0.001). Conclusions Two thirds of patients were readmitted within the first 14 days after STEMI , and a large proportion of patients were readmitted for noncardiac reasons. Thirty-day readmission was associated with an ≈50% increase in cumulative hospitalization costs. These findings highlight the importance of closer surveillance of both cardiac and general medical conditions in the first several weeks after STEMI discharge.

Nutritional Risk Index predicts mortality in hospitalized advanced heart failure patients.

BACKGROUND: Hospitalized advanced heart failure (HF) patients are at high risk for malnutrition and death. The Nutritional Risk Index (NRI) is a simple, well-validated tool for identifying patients at risk for nutrition-related complications. We hypothesized that, in advanced HF patients from the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial, the NRI would improve risk discrimination for 6-month all-cause mortality. METHODS: We analyzed the 160 ESCAPE index admission survivors with complete follow-up and NRI data, calculated as follows: NRI = (1.519 × discharge serum albumin [in g/dl]) + (41.7 × discharge weight [in kg] / ideal body weight [in kg]); as in previous studies, if discharge weight is greater than ideal body weight (IBW), this ratio was set to 1. The previously developed ESCAPE mortality model includes: age; 6-minute walk distance; cardiopulmonary resuscitation/mechanical ventilation; discharge ß-blocker prescription and diuretic dose; and discharge serum sodium, blood urea nitrogen and brain natriuretic peptide levels. We used Cox proportional hazards modeling for the outcome of 6-month all-cause mortality. RESULTS: Thirty of 160 patients died within 6 months of hospital discharge. The median NRI was 96 (IQR 91 to 102), reflecting mild-to-moderate nutritional risk. The NRI independently predicted 6-month mortality, with adjusted HR 0.60 (95% CI 0.39 to 0.93, p = 0.02) per 10 units, and increased Harrell's c-index from 0.74 to 0.76 when added to the ESCAPE model. Body mass index and NRI at hospital admission did not predict 6-month mortality. The discharge NRI was most helpful in patients with high (≥ 20%) predicted mortality by the ESCAPE model, where observed 6-month mortality was 38% in patients with NRI < 100 and 14% in those with NRI > 100 (p = 0.04). CONCLUSIONS: The NRI is a simple tool that can improve mortality risk stratification at hospital discharge in hospitalized patients with advanced HF.

Nanoimmunoassay to Detect Responses in Head and Neck Cancer: Feasibility in a Mouse Model.

OBJECTIVE: To demonstrate the feasibility of detecting and quantifying extracellular signal-related kinase (ERK) phosphorylation status using nanoimmunoassay (NIA). STUDY DESIGN: Analyses using Cal27, SCC25, and OSC19 head and neck squamous carcinoma cell lines in vitro and in a murine xenograft model. SUBJECTS AND METHODS: NIA and immunoblot were performed on whole-cell lysates, tumor lysates, and fine-needle aspirate biopsies to detect ERK phosphorylation states. RESULTS: Using NIA, all 6 isoforms of ERK1/2, including nonphosphorylated, monophosphorylated, and diphosphorylated species, could be reliably detected, distinguished, and quantified in a single assay using a single antibody. In vitro treatment of Cal27 cells with the epidermal growth factor receptor inhibitor gefitinib abolished phospho-ERK detection by immunoblot but resulted in residual detectable species by NIA. Residual phospho-ERK in gefitinib-treated cells could be further reduced by the addition of the insulin-like growth factor 1 receptor inhibitor OSI-906; this correlated with an additional decrease in proliferation over gefitinib alone. In a pilot study of 4 murine xenograft tumors, NIA performed on tumor lysates and fine-needle aspirate biopsies demonstrated altered ERK profiles after 2 days of gefitinib treatment compared with untreated mice. CONCLUSION: NIA offers a novel approach to quantitating the activation state of signaling molecules such as ERK in nanoscale in vitro and in vivo samples across a wide dynamic range. As such, it has potential to provide molecular diagnostic information before, during, and after treatment using a minimally invasive technique. Further study is warranted to determine its utility in assessing signaling proteins as biomolecular outcome predictors in clinical trials.