Epithelial-Mesenchymal Transition Markers in Breast Cancer and Pathological Responseafter Neoadjuvant Chemotherapy.

The association between pathologic complete response (pCR) following to neoadjuvant chemotherapy (NAC) and the improved survival in breast cancer has been previously reported. The aim of this study was is to explore the expression of several biomarkers described during epithelial-mesenchymal transition (EMT) and the achievement of pCR in different molecular subtypes of breast cancer. We identified archived pathology tissue from patients with breast cancer who received NAC during the year 2014. We performed immunohistochemical analysis of vimentin, nuclear factor κB (NF-κB), epidermal growth factor receptor (EGFR), E-cadherin, estrogen receptor (ER), progesterone receptor, and Her2neu and studied the association between the expression of these markers and pCR. A Fisher exact test for categorical cofactors, an unpaired t test and a nonparametric Wilcoxon test for continuous cofactors were used. The results showed a significant expression of vimentin in triple-negative breast cancer (TNBC; P = .023). An inverse correlation between vimentin and the ER expression (P = .032) was observed. No significant association was noted for vimentin, NF-κB, EGFR, and E-cadherin was associated with pCR. This study suggests that the evaluated EMT related biomarkers are not associated with pCR after NAC chemotherapy in an unselected breast cancer population. Vimentin and NF-κB expressions were associated with TNBC and could be further explored as potential therapeutic targets in this subgroup. A prevalence of vimentin and NF-κB among Hispanic patients with breast cancer warrants further investigation as a possibly contributing to the prevalence of TNBC and adverse prognosis in this population.

The Basic Metabolic Profile in Heart Failure-Marker and Modifier.

PURPOSE OF REVIEW: The physiologic determinants of each of the components of the basic metabolic profile in patients with heart failure will be explored. Additionally, the review will discuss the prognostic value of alterations in the basic metabolic profile as well as their effects on management. RECENT FINDINGS: Abnormalities in the basic metabolic profile have significant correlation with clinical outcomes and can modify treatment in heart failure. Hypochloremia has recently received increased attention for these reasons. Elevated creatinine, increased blood urea nitrogen, hyponatremia, and hypochloremia correlate with worse mortality and diuretic resistance in heart failure. Hypokalemia, even when mild, has proven to be a worse clinical indicator than modest elevations in serum potassium. Hypochloremia is mechanistically linked to hyponatremia and metabolic alkalosis, but recent compelling data suggests that it can provide more discriminating prognostic information. Knowledge of the physiologic basis for each of these alterations informs their management.

An assessment of the safety, hemodynamic response, and diagnostic accuracy of commonly used vasodilator stressors in patients with severe aortic stenosis.

BACKGROUND: Increasing numbers of patients are undergoing transcatheter aortic valve replacement, which often involves assessment of coronary artery disease ischemic burden. The safety and diagnostic accuracy of vasodilator stress agents in patients with severe aortic stenosis (AS) undergoing SPECT myocardial perfusion imaging (MPI) has not been established. METHODS: Patients with severe AS (valve area <1 cm2) on echocardiography who underwent vasodilator stress SPECT MPI at two centers were identified. Patients with aortic valve intervention prior to MPI or who underwent concurrent exercise during stress testing were excluded. AS patients were matched to controls without AS based on age, gender, BMI, ejection fraction, and stress agent. Symptoms, serious adverse events, hemodynamic response, and correlation to invasive angiography were assessed. RESULTS: A total of 95 cases were identified with 45% undergoing regadenoson, 31% dipyridamole, and 24% adenosine stress. A significant change in systolic blood pressure (BP), cases vs controls, was observed with adenosine [-17.9 ± 20.1 vs -2.6 ± 24.9 P = .03)], with a trend toward significance with regadenoson [-16.8 ± 20.3 vs -9.4 ± 17.9 (P = .08)] and dipyridamole [-17.8 ± 20.6 vs -9.0 ± 12.1 (P = .05)]. The change in heart rate was significantly different only for adenosine [5.3 ± 16.8 vs 14.2 ± 10.8 (P = .04)]. Overall, 45% of cases vs 24% of controls (P = .004) had a >20 mmHg decrease in systolic BP. Age, BMI, and resting systolic BP were related to a >20 mmHg decrease in systolic BP on univariate analysis, although only higher resting systolic BP was a predictor on multivariate analysis. In 33 patients who underwent angiography, the sensitivity, specificity, and diagnostic accuracy of vasodilator stress MPI was 77%, 69%, and 73%, respectively. No serious adverse events occurred in the severe AS patients. CONCLUSION: Severe AS patients are more likely to have a hemodynamically significant decrease in systolic BP with vasodilator stress. There were no serious adverse events in this severe AS cohort with good diagnostic performance of MPI compared to angiography.

Glycemic Control and Excess Cardiovascular Mortality in Type 1 Diabetes.

Diabetes mellitus is a chronic systemic disease with multiple complications ranging from microvascular to macrovascular diseases. Type 1 diabetes comprises 5 % of adults with diabetes in the US. This population is shown to be at increased risk of cardiovascular events and mortality. Intensive glycemic control has been consistently associated with decreased microvascular complications but trials on macrovascular benefit yielded mixed results over the years. Recent data from long-term observational follow-up studies of major diabetes cardiovascular events and mortality are showing benefits that were not seen with the initial interventional trials. This article will review evidence on the effect of glycemic control on complications in diabetes mellitus with a focus on cardiovascular mortality in type 1 diabetes.

Recurrent myopericarditis as a complication of Marijuana use.

PATIENT: Male, 29 FINAL DIAGNOSIS: Myopericarditis Symptoms: Chest pain Medication: Ibuprofen Clinical Procedure: - Specialty: Cardiology. OBJECTIVE: Unusual clinical course. BACKGROUND: Cannabis is the most commonly used illegal substance worldwide and its consumption portends significant side effects. Nowadays, in order to increase its psychotropic effect, various substances are being added constantly to it to promote its potency that might hold toxic effects to different organs including the heart and might lead to other unreported complications such as myopericarditis. Herein, we are presenting a unique case of recurrent myopericarditis after the consumption of contaminated marijuana, an association that has not been reported in literature before. CASE REPORT: A 29-year-old man presented to our institution with pressure-like left-sided chest pain that is aggravated by cough and deep inspiration and relieved by sitting and leaning forward. Examination revealed pericardial rub and workup showed elevated white blood cell count, C-reactive protein and troponin I level of 2.99 ng/ml. ECG upon admission showed ST-segment elevation in the inferior leads with PR-segment depression. Echocardiogram revealed only concentric hypertrophy. PATIENT was admitted to another institution with similar symptoms 2 months earlier. PATIENT admitted to using adulterated Marijuana on both occasions prior to hospitalization. Review of medical records from the outside hospital revealed similar ECG and laboratory findings. Treatment with Ibuprofen resulted in resolution of patient's symptoms and ECG abnormalities. CONCLUSIONS: Recurrent myopericarditis in our patient is likely the result of consumption of contaminated Marijuana. Careful history taking in patients presenting with myopericarditis is crucial as it might be the causal link.

Serum amyloid A renal amyloidosis in a chronic subcutaneous ("skin popping") heroin user.

BACKGROUND: Systemic AA amyloidosis is a long-term complication of several chronic inflammatory disorders. Organ damage results from the extracellular deposition of proteolytic fragments of the acute-phase reactant serum amyloid A (SAA) as amyloid fibrils. Drug users that inject drug by a subcutaneous route ("skin popping") have a higher chance of developing secondary amyloidosis. The kidneys, liver, and spleen are the main target organs of AA amyloid deposits. More than 90% of patients with renal amyloidosis will present with proteinuria, nephrotic syndrome, or renal function. CASE PRESENTATION: A 37 year-old female presented to the hospital with a one-week history of pain and redness in her right axilla. Her relevant medical history included multiple skin abscesses secondary to "skin popping", heroin abuse for 18 years, and hepatitis C. The physical examination revealed "skin popping" lesions, bilateral costovertebral angle tenderness, and bilateral knee swelling. The laboratory workup was significant for renal insufficiency with a serum creatinine of 5 mg/dL and 14.8 grams of urine protein per 1 gram of urine creatinine. The renal biopsy findings were consistent with a diagnosis of renal amyloidosis due to serum amyloid A deposition and acute tubulointerstitial nephritis. CONCLUSIONS: AA renal amyloidosis among heroin addicts seems to be associated with chronic suppurative skin infection secondary to "skin popping". It is postulated that the chronic immunologic stimulation by one or more exogenous antigens or multiple acute inflammatory episodes is an important factor in the pathogenesis of amyloidosis in these patients. Therefore, AA renal amyloidosis should always be considered in chronic heroin users presenting with proteinuria and renal impairment.

PPAR- γ agonist in treatment of diabetes: cardiovascular safety considerations.

The peroxisome proliferator-activated receptors (PPARs) are nuclear fatty acid receptors, which contain a type II zinc finger DNA binding motif and a hydrophobic ligand binding pocket. These receptors are thought to play an important role in metabolic diseases such as obesity, insulin resistance, and coronary artery disease. Three subtypes of PPAR receptors have been described: PPARα, PPARδ/ß, and PPARγ. PPARα is found in the liver, muscle, kidney, and heart. In the liver, its role is to up-regulate genes involved in fatty acid uptake, binding, ß-oxidation and electron transport, and oxidative phosphorylation in subcutaneous fat but not in skeletal muscle. PPARδ/ß is expressed in many tissues but markedly in brain, adipose tissue, and skin. PPARγ has high expression in fat, low expression in the liver, and very low expression in the muscle. The thiazolidinediones (TZD) are synthetic ligands of PPARγ. By activating a number of genes in tissues, PPARγ increases glucose and lipid uptake, increases glucose oxidation, decreases free fatty acid concentration, and decreases insulin resistance. Although, there is a rationale for the use of TZDs in patients with type 2 diabetes mellitus, clinical studies have produced conflicting data. While currently used TZDs are clearly associated with heart failure (HF) worsening; with regards to cardiovascular outcomes, pioglitazone seems to be related to a trend toward reduction in cardiovascular morbidity and mortality, whereas rosiglitazone may actually increase risk of cardiovascular events. We review the existing literature on TZDs and discuss role and cardiovascular safety of these agents for the contemporary treatment of diabetes. Other side effects of these agents i.e. increase in osteoporosis and possible risk of bladder cancer is also discussed.