Left Ventricular Septal Hypertrophy in Elderly Patients With Aortic Stenosis.

OBJECTIVES: Left ventricular (LV) septal hypertrophy in aortic stenosis raises diagnostic and therapeutic questions. However, the etiology and clinical consequences of this finding have not been well studied. The aim of this study was to perform a morphologic evaluation of the LV in aortic stenosis and to investigate the contributing factors and consequences of septal hypertrophy. METHODS: Patients with moderate or severe aortic stenosis were prospectively enrolled. Patients with previous myocardial infarction, wall motion abnormalities, at least moderate valvular regurgitation, known cardiomyopathy, an LV ejection fraction of less than 50%, and age younger than 65 years were excluded. RESULTS: Forty-one patients underwent a final analysis. Septal hypertrophy (LV septal wall thickness ≥15 mm) was confirmed in 21 of 41 patients. The septal hypertrophy group had higher peak aortic valve velocity, a higher diabetes mellitus rate, and a higher rate and longer duration of hypertension than those without septal hypertrophy. The peak aortic valve velocity (odds ratio, 7.1; 95% confidence interval, 1.4-37.1) and diabetes mellitus (odds ratio, 7.4; 95% confidence interval, 1.2-46.2) were the significant factors associated with septal hypertrophy by multivariate analysis. Intraventricular conduction disturbance on electrocardiography was more frequent in the septal hypertrophy group (P = .021). CONCLUSIONS: Left ventricular septal hypertrophy was commonly observed in elderly patients with aortic stenosis, and a higher aortic valve velocity, hypertension, and diabetes mellitus were associated factors. Intraventricular conduction disturbance occurred more often in patients with septal hypertrophy than those without, which implies the pathophysiologic consequence. Further studies are needed to determine the impact of septal hypertrophy and intraventricular conduction disturbance on the prognosis of patients after aortic valve interventions.

Variability and accuracy of different software packages for dynamic susceptibility contrast magnetic resonance imaging for distinguishing glioblastoma progression from pseudoprogression.

Determining whether glioblastoma multiforme (GBM) is progressing despite treatment is challenging due to the pseudoprogression phenomenon seen on conventional MRIs, but relative cerebral blood volume (CBV) has been shown to be helpful. As CBV's calculation from perfusion-weighted images is not standardized, we investigated whether there were differences between three FDA-cleared software packages in their CBV output values and subsequent performance regarding predicting survival/progression. Forty-five postradiation therapy GBM cases were retrospectively identified as having indeterminate MRI findings of progression versus pseudoprogression. The dynamic susceptibility contrast MR images were processed with different software and three different relative CBV metrics based on the abnormally enhancing regions were computed. The intersoftware intraclass correlation coefficients were 0.8 and below, depending on the metric used. No statistically significant difference in progression determination performance was found between the software packages, but performance was better for the cohort imaged at 3.0 T versus those imaged at 1.5 T for many relative CBV metric and classification criteria combinations. The results revealed clinically significant variation in relative CBV measures based on the software used, but minimal interoperator variation. We recommend against using specific relative CBV measurement thresholds for GBM progression determination unless the same software or processing algorithm is used.

Treatment of Endometriosis with the GnRHa Deslorelin and Add-Back Estradiol and Supplementary Testosterone.

BACKGROUND: This randomized, multicenter, open-label clinical trial was intended to generate pilot data on the efficacy and safety of the gonadotropin-releasing hormone agonist (GnRHa) deslorelin (D) with low-dose estradiol ± testosterone (E2 ± T) add-back for endometriosis-related pelvic pain. METHODS: Women with pelvic pain and laparoscopically confirmed endometriosis were treated with a six-month course of daily intranasal D with concurrent administration of either transdermal E2, intranasal E2, or intranasal E2 + T. Efficacy data included evaluation of dyspareunia, dysmenorrhea, pelvic pain, tenderness, and induration. Cognition and quality of life were also assessed. Safety parameters included assessment of endometrial hyperplasia, bone mineral density (BMD), and hot flashes. RESULTS: Endometriosis symptoms and signs scores decreased in all treatment arms from a baseline average of 7.4 to 2.5 after 3 months of treatment and 3.4 after 6 months. BMD changes and incidence of hot flashes were minimal, and no endometrial hyperplasia was observed. Patient-reported outcomes showed significant improvement across multiple domains. CONCLUSIONS: Daily intranasal D with low dose E2 ± T add-back resulted in significant reduction in severity of endometriosis symptoms and signs with few safety signals and minimal hypoestrogenic symptoms that would be expected with the use of a GnRHa alone.

Subselective intra-arterial chemotherapy infusion in the treatment of hepatocellular carcinoma.

Intra-arterial delivery of chemotherapy is a well-established dominant treatment for hepatocellular carcinoma (HCC). This approach takes advantage of differential blood supply to the cancer, which is arterial, and to the liver, which is predominantly portal. Randomized trials demonstrating survival benefit have used transarterial chemoembolization (TACE) with arrest of blood flow and arterial obstruction to increase efficiency of drug delivery. Treatment-associated morbidity is significant but usually justified by the patient benefit. A number of alternative embolic particles have been explored to address efficacy and toxicity deficiencies of the original technology. In this article we list those materials. We then develop evidence that sub-selective arterial infusion therapy without embolic agents provides equivalent efficacy with less treatment morbidity.

Reduced mammographic density with use of a gonadotropin-releasing hormone agonist-based chemoprevention regimen in BRCA1 carriers.

PURPOSE: Women with a BRCA1 mutation (BRCA1(mut)) need risk reduction options beyond mastectomy and oophorectomy. We evaluated the efficacy, safety, and tolerability of hormonal chemoprevention with a gonadotropin-releasing hormone agonist (GnRHA) with low-dose add-back steroids in BRCA1(mut) carriers. EXPERIMENTAL DESIGN: The 12-month open label clinical trial used the GnRHA deslorelin, ultra-low-dose estradiol (E(2)), and replacement testosterone, administered via daily intranasal spray in premenopausal women with a BRCA1(mut), and intermittent oral medroxyprogesterone acetate. The end points included mammographic percent density, bone mineral density, endometrial hyperplasia, symptom inventory, and quality of life (Medical Outcomes SF-36 survey). RESULTS: Six of eight BRCA1(mut) women (mean age, 30.3 years; range, 25-36 years) completed the study. Mammographic percent density was significantly reduced at 12 months (median absolute mammographic percent density decrease, 8.3%; P = 0.043), representing a 29.2% median reduction in mammographic percent density. Bone mineral density remained within reference limits for all participants; there were no cases of atypical endometrial hyperplasia and menses resumed within a median of 67 days (range, 35-110 days) after last drug treatment day. The treatment was well tolerated; hypoestrogenic side effects were minimal and transient; and there were no significant changes in quality of life. CONCLUSIONS: The GnRHA deslorelin, with low-dose add-back steroids, was well tolerated and significantly decreased mammographic percent density in BRCA1(mut) carriers. This regimen may reduce breast cancer risk and improve the usefulness of mammographic surveillance by reducing density. This is the first demonstration, to our knowledge, of a direct reduction of mammographic densities in young BRCA1(mut) carriers.