Glycogen-rich Clear Cell Carcinoma of the Breast: A Comprehensive Review.

Glycogen-rich clear cell carcinoma (GRCC) is a very rare form of primary breast cancer (<0.1% of all breast cancers). It is characterized by the presence of neoplastic cells with a glycogen-abundant clear cytoplasm (the Periodic Acid Schiff-positive, diastase-sensitive). The expression of steroid receptors (estrogen and progesterone receptors) has been variably reported (35% to 100% of the cases), whereas most studies reported low human epidermal growth factor receptor 2 positivity in GRCC. High androgen receptor positivity without androgen receptor splice variant-7 was reported in one recent study. Although sparse, the preliminary theranostic data on GRCC indicate the potential of targeted treatments in selected cases (antiandrogen, PIK3CA, and immune checkpoint inhibitors). Because of its rarity, the prognosis for GRCC patients remains controversial. Herein, we comprehensively appraise the epidemiological, morphologic, molecular, and clinical characteristics of this rare mammary malignancy

Pushing the Limits of Medical Management in HCM: A Review of Current Pharmacological Therapy Options

Hypertrophic cardiomyopathy (HCM) is the most common monogenic cardiac disease with a highly variable phenotypic expression, ranging from asymptomatic to drug refractory heart failure (HF) presentation. Pharmacological therapy is the first line of treatment, but options are currently limited to nonspecific medication like betablockers or calcium channel inhibitors, with frequent suboptimal results. While being the gold standard practice for the management of drug refractory HCM patients, septal reduction therapy (SRT) remains an invasive procedure with associated surgical risks and it requires the expertise of the operating centre, thus limiting its accessibility. It is therefore with high interest that researchers look for pharmacological alternatives that could provide higher rates of success. With new data gathering these past years as well as the development of a new drug class showing promising results, this review provides an up-to-date focused synthesis of existing medical treatment options and future directions for HCM pharmacological treatment

Beta-Blocker-Related Atrioventricular Conduction Disorders—A Single Tertiary Referral Center Experience

Background and Objectives: Drug-related bradyarrhythmia is a well-documented major adverse event among beta-blocker users and a potential cause for hospitalization or additional interventions. Whether beta-blocker use is associated with specific bradyarrhythmia presentations, and how this relates to other predisposing factors, is not well known. We aim to evaluate the association between beta-blocker use and the type of atrioventricular (AV) conduction disorder in patients with symptomatic bradycardia. Materials and Methods: We conducted a retrospective cohort study on 596 patients with a primary diagnosis of symptomatic bradyarrhythmia admitted to a single tertiary referral center. Of the cases analyzed, 253 patients were on beta-blocker treatment at presentation and 343 had no bradycardic treatment. We analyzed demographics, clinical and paraclinical parameters in relation to the identified AV conduction disorder. A multivariate regression analysis was performed to explore factors associated with beta-blocker use. Results: Of the 596 patients (mean age 73.9 ± 8.8 years, 49.2% male), 261 (43.8%) had a third-degree AV block, 92 (15.4%) had a second-degree AV block, 128 (21.5%) had slow atrial fibrillation, 93 (15.6%) had sick sinus syndrome and 21 (3.5%) had sinus bradycardia/sinus pauses. Beta-blocker use was associated with the female gender (p p p = 0.003), the lower left ventricular ejection fraction (p = 0.02), mitral stenosis (p = 0.009), chronic kidney disease (p = 0.02), higher potassium levels (p = 0.04) and QRS duration > 120 ms (p = 0.02). Slow atrial fibrillation (OR = 4.2, p p = 0.001) and sinus bradycardia/pauses (OR = 32.9, p Conclusions: Beta-blocker use is more likely to be associated with slow atrial fibrillation, sick sinus syndrome and sinus bradycardia/pauses, compared to a second- or third-degree AV block, after adjusting for other patient factors such as gender, admission type, ECG, comorbidities, cardiac function and lab testing

Targeted deletion of kcne2 impairs ventricular repolarization via disruption of IK,slow1 and Ito,f

Mutations in human KCNE2, which encodes the MiRP1 potassium channel ancillary subunit, associate with long QT syndrome (LQTS), a defect in ventricular repolarization. The precise cardiac role of MiRP1 remains controversial, in part, because it has marked functional promiscuity in vitro. Here, we disrupted the murine kcne2 gene to define the role of MiRP1 in murine ventricles. kcne2 disruption prolonged ventricular action potential duration (APD), suggestive of reduced repolarization capacity. Accordingly, kcne2 (−/−) ventricles exhibited a 50% reduction in IK,slow1, generated by Kv1.5—a previously unknown partner for MiRP1. Ito,f, generated by Kv4 α subunits, was also diminished, by ∼25%. Ventricular MiRP1 protein coimmunoprecipitated with native Kv1.5 and Kv4.2 but not Kv1.4 or Kv4.3. Unexpectedly, kcne2 (−/−) ventricular membrane fractions exhibited 50% less mature Kv1.5 protein than wild type, and disruption of Kv1.5 trafficking to the intercalated discs. Consistent with the reduction in ventricular K+ currents and prolonged ventricular APD, kcne2 deletion lengthened the QTc under sevoflurane anesthesia. Thus, targeted disruption of kcne2 has revealed a novel cardiac partner for MiRP1, a novel role for MiRPs in α subunit targeting in vivo, and a role for MiRP1 in murine ventricular repolarization with parallels to that proposed for the human heart.—Roepke, T. K., Kontogeorgis, A., Ovanez, C., Xu, X., Young, J. B., Purtell, K., Goldstein, P. A., Christini, D. J., Peters, N. S., Akar, F. G., Gutstein, D. E., Lerner, D. J., Abbott, G. W. Targeted deletion of kcne2 impairs ventricular repolarization via disruption of IK,slow1 and Ito,f