Crinkle-Cut Coronary Arteries in a Patient With Granulomatosis With Polyangiitis.

Granulomatosis with polyangiitis (GPA) is a rare type of small to medium vessel necrotizing vasculitis that usually affects vessels of the upper or lower airways and kidneys. Cardiac involvement in GPA is often subclinical and if clinically significant has been rarely reported, even less so as an initial presentation. We describe the case of a 44-year-old man who presented with what appeared to be inferior ST-segment elevation myocardial infarction and was found to have small vessel vasculitis of the coronary arteries with associated myocarditis as a presenting manifestation of GPA, which was ultimately treated with steroids, rituximab, and avacopan.

Correction to: Targeted degradation of activating estrogen receptor α ligand-binding domain mutations in human breast cancer.

In the original publication of the article, the spelling of the sixth author's given name was incorrect. The corrected author name should read as "Wadie David". The original article has been corrected.

Targeted degradation of activating estrogen receptor α ligand-binding domain mutations in human breast cancer.

PURPOSE: Studies have identified several estrogen receptor α (ERα) ligand-binding domain (LBD) somatic mutations in endocrine therapy resistant, metastatic ER-positive breast cancers. The most common mutations, Tyr537Ser (Y537S) and Asp538Gly (D538G), are detected in ~ 30% of endocrine resistant metastatic breast cancer patients. These ESR1 mutations induce the agonist conformation of ERα, confer an estrogen-independent phenotype, and promote drug resistance to antiestrogens. METHODS: ER-positive, estrogen-dependent MCF-7 cells were engineered to express either the Y537S or D538G mutants using CRISPR knock-in (cY537S and cD538G). These cells were used to screen several estrogen receptor degrader (ERD) compounds synthesized using the Proteolysis Targeting Chimeras (PROTAC) method to induce degradation of ERα via the ubiquitin-proteasome pathway. RESULTS: Wild-type MCF-7 and ERα LBD mutant cells were treated with ERD-148 (10 pM-1 µM) and assayed for cellular proliferation using the PrestoBlue cell viability assay. ERD-148 attenuated ER-dependent growth with IC50 values of 0.8, 10.5, and 6.1 nM in MCF-7, cY537S, and cD538G cells, respectively. Western blot analysis showed that MCF-7 cells treated with 1 nM ERD-148 for 24 h exhibited reduced ERα protein expression as compared to the mutants. The ER-regulated gene, GREB1, demonstrated significant downregulation in parental and mutant cells after 24 h of ERD-148 treatment at 10 nM. Growth of the ER-negative, estrogen-independent MDA-MB-231 breast cancer cells was not inhibited by ERD-148 at the ~ IC90 observed in the ER-positive cells. CONCLUSION: ERD-148 inhibits the growth of ER-positive breast cancer cells via downregulating ERα with comparable potency to Fulvestrant with marginal non-specific toxicity.

Inverted Yoga and Near Syncope: An Unusual Diagnosis of Right Ventricular Myxoma.

Primary cardiac tumors are extremely rare and are difficult to diagnose. Although usually benign in nature, myxomas require surgical resection due to their increased risk of embolic and cardiac complications, with the timing of resection dependent on the presentation and size of the tumor. However, if diagnosed early, patients with primary benign cardiac tumors have excellent prognosis following surgery. Therefore, a high index of suspicion and a wide differential diagnosis are very important in detecting rare conditions that can affect otherwise healthy individuals. We present an uncommon case of a right ventricular myxoma that was discovered when the patient was performing inverted yoga and experienced a near syncopal episode. Patient subsequently underwent an echocardiographic evaluation and was found to have a right ventricular myxoma that was excised. Although recurrence is rare, it is important for physicians to remain vigilant and continue careful and consistent follow-up for patients with a history of a cardiac myxoma.

Unloading of right ventricle and clinical improvement after ultrasound-accelerated thrombolysis in patients with submassive pulmonary embolism.

Acute pulmonary embolism (PE) can be devastating. It is classified into three categories based on clinical scenario, elevated biomarkers, radiographic or echocardiographic features of right ventricular strain, and hemodynamic instability. Submassive PE is diagnosed when a patient has elevated biomarkers, CT-scan, or echocardiogram showing right ventricular strain and no signs of hemodynamic compromise. Thromboemboli in the acute setting increase pulmonary vascular resistance by obstruction and vasoconstriction, resulting in pulmonary hypertension. This, further, deteriorates symptoms and hemodynamic status. Studies have shown that elevated biomarkers and right ventricular (RV) dysfunction have been associated with increased risk of mortality. Therefore, aggressive treatment is necessary to "unload" right ventricle. The treatment of submassive PE with thrombolysis is controversial, though recent data have favored thrombolysis over conventional anticoagulants in acute setting. The most feared complication of systemic thrombolysis is intracranial or major bleeding. To circumvent this problem, a newer and safer approach is sought. Ultrasound-accelerated thrombolysis is a relatively newer and safer approach that requires local administration of thrombolytic agents. Herein, we report a case series of five patients who underwent ultrasound-accelerated thrombolysis with notable improvement in symptoms and right ventricular function.

Primary hyperaldosteronism decoded: a case of curable resistant hypertension.

Patients with resistant hypertension have a higher incidence of secondary causes of hypertension compared with the general hypertensive population. It is important to screen such patients for secondary causes of hypertension because appropriate treatment can lead to improved blood pressure control or even cure these patients, and thus avoid the cardiovascular morbidity and mortality associated with uncontrolled hypertension. One common cause of secondary hypertension, often associated with hypokalemia, is primary hyperaldosteronism or Conn syndrome. Aldosterone is a mineralocorticoid hormone produced in the outer layer of the adrenal cortex (the zona glomerulosa); its primary action is to increase sodium and water reabsorption by the kidney. Once the diagnosis of primary aldosteronism is made, it is necessary to determine if aldosterone production is unilateral or bilateral. When production is unilateral (most often from a functional adenoma), surgery is potentially curative. The authors report a case and review the diagnostic workup of Conn syndrome in which resistant hypertension and hypokalemia were cured by unilateral adrenalectomy.

Emerging practice patterns and outcomes of percutaneous aortic balloon valvuloplasty in patients with severe aortic stenosis.

A total of 33 patients with severe aortic stenosis undergoing percutaneous aortic balloon valvuloplasty (PABV) for bridging or palliative therapy were reviewed; the emerging treatment patterns for this procedure are described. Longitudinal data suggest that PABV provides a significant reduction in peak and mean aortic valve gradients with > 12-month survival for more than half of observed patients. This supports the current application of PABV, which is currently limited to palliative care and bridging therapy to more definitive forms of future treatment, including transcatheter aortic valve implantation.