Unsafe Drug Use and Arrhythmic Events in Brugada Patients with ICD: Results of a Long-Term Follow-Up

Purpose

Brugada syndrome is a hereditary disease linked with an increased risk of sudden death that may require an implantable cardioverter-defibrillator (ICD) in order to halt the arrhythmic events. The aim of this study was to identify possible triggers for appropriate ICD therapies in patients with Brugada syndrome, focusing on their past and current therapeutic profiles.

Methods

Thirty patients with high-risk Brugada syndrome, with ICD implanted at the Coimbra Hospital and University Center, were enrolled. Patients were questioned about their Brugada syndrome history, previous cardiac events, comorbidities, present and past medications, and physical activity. Patients were followed up during 5.8?±?5.3 years. The ICD was interrogated, and arrhythmic events and device therapies were recorded. The cohort who received appropriate ICD therapies was compared with the remaining patients to determine the potential link between clinical variables and potentially fatal arrhythmic events.

Results

More than half of the patients (53.3%) took at least one non-recommended drug, and 16.7% received appropriate ICD therapies, with a long-term rate of 4.0%/year. There was a tendency for more appropriate ICD therapies in patients who took unsafe drugs (85.7 versus 45.5%, p?=?0.062), and the mean time between unsafe drug intake and appropriate ICD therapies was 3.8?±?7.5 days.

Conclusions

This study revealed that the medical community is still unaware of the pharmacological restrictions imposed by Brugada syndrome. Patients who took non-recommended drugs seem to have a higher risk of ventricular arrhythmic events.

     

Monocyte and Lymphocyte Activation in Bipolar Disorder: A New Piece in the Puzzle of Immune Dysfunction in Mood Disorders

Background:

This study tested the hypothesis that the low-grade inflammation presented in patients with bipolar disorder (BD) is associated with expansion of activated T cells, and this activated state may be due to a lack of peripheral regulatory cells.

Methods:

Specifically, we investigated the distribution of monocytes and lymphocyte subsets, and investigated Th1/Th2/Th17 cytokines in plasma by flow cytometry. Twenty-one BD type I patients and 21 age- and sex-matched controls were recruited for this study.

Results:

BD patients had increased proportions of monocytes (CD14+). Regarding lymphocyte populations, BD patients presented reduced proportions of T cells (CD3+) and cytotoxic T cells (CD3+CD8+). BD patients also exhibited a higher percentage of activated T CD4+CD25+ cells, and a lower percentage of IL-10 expressing Treg cells.

Conclusions:

Our data shed some light into the underlying mechanisms involved with the chronic low-grade inflammatory profile described in BD patients.     

Increased HLA-G Expression in Tissue-Infiltrating Cells in Inflammatory Bowel Diseases

Background

Since HLA-G is an immune checkpoint molecule and since Crohn’s disease (CD) and ulcerative colitis (UC) exhibit deregulated immune-mediated mechanisms, we aimed to evaluate intestinal HLA-G expression and soluble HLA-G (sHLA-G) levels in CD/UC patients stratified according to the CD phenotype/localization and UC extension.

Methods

HLA-G tissue expression was assessed by immunohistochemistry in biopsies collected from 151 patients (90 CD, 61 UC) and in surgical resection specimens (28 CD, 12 UC). Surgical material from 24 healthy controls was also assessed. Plasma sHLA-G levels (97 CD, 81 UC, and 120 controls) were evaluated using ELISA.

Results

HLA-G expression was similarly observed in the intestinal epithelial cells of control and CD/UC specimens. However, in biopsies, the plasma cells/lymphocytes infiltrating the lamina propria in CD/UC presented (1) increased HLA-G expression compared to controls (P?<?0.0001), (2) greater cell staining in UC cells than in CD cells irrespective of disease extent (P?=?0.0011), and (3) an increased number of infiltrating cells in the inflammatory CD phenotype compared to that in the stenosing and fistulizing phenotypes (P?=?0.0407). In surgical specimens, CD/UC patients exhibited higher infiltrating cell HLA-G expression in lesion areas than in margins. sHLA-G levels were higher in UC/CD patients (P?<?0.0001) than in controls, but no difference was observed between diseases.

Conclusions

Increased infiltrating cell HLA-G expression associated with increased sHLA-G levels in CD/UC patients may reflect ongoing host strategies to suppress chronic inflammation.

     

Sex differences in uric acid metabolism in adults: evidence for a lack of influence of estradiol-17 beta (E2) on the renal handling of urate

The serum urate concentration of adult women, which is lower than in men of a similar age, is thought to be related to a higher renal clearance of urate in women, possibly due to their higher plasma estrogen levels. Intersexual differences in the renal handling of uric acid was assessed in 9 normal adult women and 9 normal age-matched men. Women showed a significantly lower serum urate concentration as compared to men (3.5 +/- 0.3 v 4.9 +/- 0.7 mg/dL, P less than 0.001), higher fractional excretion of urate (9.8 +/- 1.0 v 7.3 +/- 0.8%, P less than 0.001), and significantly lower tubular urate postsecretory reabsorption (67.2 +/- 1.6 v 76.6 +/- 1.4% of secreted urate, P less than 0.01). To test whether plasma E2 has a uricosuric effect we administered estradiol valerate and estradiol benzoate to either oophorectomized or adult women. Plasma E2 levels and urinary total estrogen excretion increased significantly in both groups but the treatment failed to significantly modify serum urate or the fractional excretion of uric acid. Furthermore, in 4 normal adult women, the tubular phases that modulate the renal excretion of urate were not significantly influenced by increased plasma E2 levels. We conclude that in comparison to men of a similar age, the lower tubular urate postsecretory reabsorption of adult women is in accordance with the intersexual differences in uric acid metabolism. Plasma E2 does not influence renal handling of uric acid or serum urate levels.     

A Specific Angiographic View of Left Coronary Artery Bifurcation in the Left Main Percutaneous Coronary Intervention Era

Objectives

We propose a right lateral (90–120° RAO) with 30° cranial angiographic view to expose the bifurcation of the left main coronary artery (LMCA) when previously used routine projections were inefficient at clearly showing this region.

Background

Little has been published in the medical literature regarding angiographic projections dedicated to special anatomies.

Methods

A total of 84 patients were subjected to the proposed projections. A reproducibility study, conducted with the participation of 2 independent observers, judged the effectiveness of the proposed projection. The Prevalence and Bias Adjusted Kappa (PABAK) index, with a 95% confidence interval (CI), was used to demonstrate the intensity of intra/inter‐observer agreement.

Results

The proposed projection was efficient in 79% of the angiograms, with agreement of 0.76 (0.6–0.9; P ≤ 0.001). The origins and the proximal segments of: the anterior descending coronary artery were exposed in 89% of the angiograms, agreement of 0.86 (0.7–1.0; P ≤ 0.001); the circumflex artery were exposed in 83% of the angiograms, with agreement of 0.72 (0.5–1.0; P ≤ 0.001); and the intermediate branch, when present, were exposed in 89% of the angiograms, agreement of 0.79 (0.6–1.0; P ≤ 0.001).

Conclusion

The right lateral (90–120° RAO) with 30° cranial projection is effective, safe, and reproducible. In special situations where routine projections fail, this proposed projection can reveal important details of the anatomy of the bifurcation of the LMCA during conventional coronary angiography or be the working projection during coronary angioplasty. (J Interven Cardiol 2016;29:293–299)

     

Flow cytometric DNA ploidy and S-phase fraction correlate with histopathologic indicators of tumor behavior in colorectal carcinoma

BACKGROUND: The clinical behavior of colorectal carcinoma is highly variable without reliable predictive biomarkers. Previous reports have shown that flow cytometric DNA analysis may provide valuable prognostic information in these tumors. PURPOSE AND METHODS: This study evaluates the DNA ploidy and the S-phase fraction (SPF) on frozen samples obtained from 61 patients with colorectal carcinoma by using flow cytometry, and it correlates the data with histopathologic features known to affect disease prognosis. Tumors were classified using the World Health Organization's histologic criteria and were staged according the American Joint Committee on Cancer's classification system. Grade of the neoplasm, vascular invasion, and perineural tumor spread were evaluated in every case. RESULTS: Fifty-nine percent of tumors were aneuploid and showed statistically significant higher S-phase values than diploid tumors (22.5 vs. 11.2 percent; P < 0.00001). Mean SPF of the whole series was 17.9 (range, 4.2–44.2) percent. A statistically significant association was found between SPF values and histologic grade (P < 0.0016), nodal status (P <0.0007), distant metastasis(P < 0.0001), tumor stage (P <0.0001), venous invasion (P < 0.0002), and lymphatic permeation (P < 0.01) but not with perineural growth and infiltration of the neoplasm through the bowel wall (T). DNA ploidy correlated positively with tumor stage (P <0.03), and the association between aneuploidy and advanced stages of the disease was statistically significant. CONCLUSIONS: These findings showed that flow cytometric DNA ploidy and SPF, evaluated in fresh samples, are potentially useful parameters to estimate colorectal carcinoma biopathology. Aneuploidy and high replicative neoplastic activity correlated with histopathologic features that are commonly associated with the prognosis of colorectal carcinoma, being SPF-related to disease dissemination and, therefore, an indicator of clinical relevance.     

Body composition estimation in children and adolescents by bioelectrical impedance analysis: A systematic review

Background

Bioelectrical impedance analysis (BIA) has commonly been used to assess the body composition of children and adolescents. BIA validation studies have found distinct correlation values with reference methods.

Estimating bone mineral content based on different types of muscle strength tests

The aims of this pilot study were to verify which muscle strength tests better explain bone mineral content (BMC) of the femoral neck and lumbar spine and to develop predictive equations to estimate femoral neck and lumbar spine BMC. Twenty-nine subjects aged 56–76 years old (12 women and 17 men) participated in the study. Femoral neck and lumbar spine BMC was evaluated by Dual X-ray absorptiometry (DXA). Muscle strength measurements included maximal isometric voluntary contractions of knee extensors and flexors, vertical jump, 5-repetition maximum of the leg press (5-RM_LP) and seated leg curl (5-RM_LC), and handgrip strength. Women presented a moderate to strong correlation between femoral neck BMC and 5-RM_LP (r = 0.819), 5-RM_LC (r = 0.879), knee extensors peak torque (r = 0.699), and handgrip strength (r = 0.663), as well as between lumbar spine BMC and the 5-RM_LP test (r = 0.845) and manual grip strength (r = 0.699). For females, the 5-RM_LP and 5-RM_LC tests most fully explained femoral neck BMC (R² = 0.859) and the 5-RM_LP test and body mass explained lumbar spine density (R² = 0.757) for females. Men did not present correlations between BMC and strength variables. For females, the 5-RM_LP and 5-RM_LC variables explained the variations of femoral neck BMC, while 5-RM_LP and body mass explained lumbar spine BMC. Future studies should evaluate a larger sample size and prioritize the strength tests with a greater predictive capacity.