2019 HRS expert consensus statement on evaluation,risk stratification,and management of arrhythmogenic cardiomyopathy

Arrhythmogenic cardiomyopathy (ACM) is an arrhythmogenic disorder of the myocardium not secondary to ischemic, hypertensive, or valvular heart disease. ACM incorporates a broad spectrum of genetic, systemic, infectious, and inflammatory disorders. This designation includes, but is not limited to, arrhythmogenic right/left ventricular cardiomyopathy, cardiac amyloidosis, sarcoidosis, Chagas disease, and left ventricular noncompaction. The ACM phenotype overlaps with other cardiomyopathies, particularly dilated cardiomyopathy with arrhythmia presentation that may be associated with ventricular dilatation and/or impaired systolic function. This expert consensus statement provides the clinician with guidance on evaluation and management of ACM and includes clinically relevant information on genetics and disease mechanisms. PICO questions were utilized to evaluate contemporary evidence and provide clinical guidance related to exercise in arrhythmogenic right ventricular cardiomyopathy. Recommendations were developed and approved by an expert writing group, after a systematic literature search with evidence tables, and discussion of their own clinical experience, to present the current knowledge in the field. Each recommendation is presented using the Class of Recommendation and Level of Evidence system formulated by the American College of Cardiology and the American Heart Association and is accompanied by references and explanatory text to provide essential context. The ongoing recognition of the genetic basis of ACM provides the opportunity to examine the diverse triggers and potential common pathway for the development of disease and arrhythmia.     

A Phase II Study of Gemcitabine and Capecitabine in Advanced Cholangiocarcinoma and Carcinoma of the Gallbladder: A Single-Institution Prospective Study

Aim To determine the clinical benefit response (CBR), time to tumor progression (TTP), overall survival, and effect on quality of life (QOL) of gemcitabine and capecitabine in patients with advanced biliary cancer. Methods Gemcitabine (1000 mg/m² IV over 30 minutes on days 1 and 8) and capecitabine (650 mg/m² orally twice daily for 14 days) were administered and repeated every 21 days. All patients completed the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire and Pancreatic Cancer Module (EORTC QLQ-C30-PAN 26) questionnaire on day 1 of each cycle. Cumulative QOL scores were calculated. The two-stage design required 17 patients to evaluate the confirmed response at nine weeks. Results Twelve patients with a median age of 54 years were enrolled. A median of eight cycles per patient were completed. With a median follow-up of 18.2 months, the CBR (two partial response and five stable disease) was 58% [95% confidence interval (CI) 28–85%]. Four out of seven patients with CBR had no decline in QOL with chemotherapy. The probability of survival at one year was 0.58. Median TTP and overall survival were 9.0 and 14.0 months, respectively. Nine patients had grade 3 or 4 toxicities. There were no treatment-related deaths. Conclusions Gemcitabine and capecitabine at this dose and schedule are well tolerated and effective and may offer clinical benefit and maintain QOL in patients with advanced biliary cancer. This regimen merits further investigation in the neoadjuvant setting.     

Association of Total Cholesterol/High-Density Lipoprotein Cholesterol Ratio With Proximal Coronary Atherosclerosis Detected by Multislice Computed Tomography

The authors assessed the association between an elevated total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio (≥4) and proximal coronary artery disease (CAD), as observed on multislice computed tomography. Coronary multislice computed tomographic angiography (96% on 40- or 64-slice) was performed in 295 individuals (39% women; mean age, 54±13 years) without documented CAD who were referred for coronary evaluation. Significant CAD was defined as ≥50% stenosis in the left main, proximal left anterior descending, or ≥2 epicardial vessels. Proximal plaque was defined as presence of any plaque in left main or proximal left anterior descending vessels. Individuals with an elevated TC/HDL-C ratio vs those without had a higher prevalence of proximal plaque (62% vs 48%, P =.04) and significant CAD (19% vs 9%, P =.009). On multivariate logistic regression analysis, only age, sex, and TC/HDL-C ratio ≥4 were associated with significant CAD and proximal plaque.     

Osteochondral Interface Tissue Engineering Using Macroscopic Gradients of Bioactive Signals

Continuous gradients exist at osteochondral interfaces, which may be engineered by applying spatially patterned gradients of biological cues. In the present study, a protein-loaded microsphere-based scaffold fabrication strategy was applied to achieve spatially and temporally controlled delivery of bioactive signals in three-dimensional (3D) tissue engineering scaffolds. Bone morphogenetic protein-2 and transforming growth factor-β₁-loaded poly(d,l-lactic-co-glycolic acid) microspheres were utilized with a gradient scaffold fabrication technology to produce microsphere-based scaffolds containing opposing gradients of these signals. Constructs were then seeded with human bone marrow stromal cells (hBMSCs) or human umbilical cord mesenchymal stromal cells (hUCMSCs), and osteochondral tissue regeneration was assessed in gradient scaffolds and compared to multiple control groups. Following a 6-week cell culture, the gradient scaffolds produced regionalized extracellular matrix, and outperformed the blank control scaffolds in cell number, glycosaminoglycan production, collagen content, alkaline phosphatase activity, and in some instances, gene expression of major osteogenic and chondrogenic markers. These results suggest that engineered signal gradients may be beneficial for osteochondral tissue engineering.     

Molecular analyses of microbial diversity associated with the Lonar soda lake in India: an impact crater in a basalt area

The prokaryotic diversity associated with an Indian soda lake (Lonar Crater Lake) located in a basaltic soil area was investigated using a culture-independent approach. Community DNA was extracted directly from four sediment samples obtained by coring to depths of 10-20 cm. Small subunit rRNA genes (16S rDNA) were amplified by PCR using primers specific to the domains Bacteria and Archaea. The PCR products were cloned and sequenced. For the bacterial rDNA clone library, 500 clones were randomly selected for further analysis. After restriction fragment length polymorphism (RFLP) analysis and subsequent sequencing, a total of 44 unique phylotypes were obtained. These phylotypes spanned a wide range within the domain Bacteria, occupying eight major lineages/phyla. 34% of the clones were classified as firmicutes. The other clones were grouped into proteobacteria (29.5%), actinobacteria (6.8%), deinococcus-thermus (4.5%), cytophages-flavobacterium-bacteroidetes (13.3%), planctomycetes (6.8%), cyanobacteria (4.5%) and spirochetes (2.27%). In the case of the archaeal 16S rDNA library, analysis of 250 randomly selected clones revealed the presence of 13 distinct phylotypes; 5 phylotypes were associated with Crenarchaeota and 8 with Euryarchaeota. Most of the euryarchaeota sequences were related to methanogens. Findings from this molecular study of a site investigated for the first time have revealed the presence of a highly diverse bacterial population and a comparatively less diverse archaeal population. The majority ( approximately 80%) of the cloned sequences show little affiliation with known taxa (<97% sequence similarity) and may represent novel taxa/sequences and organisms specifically adapted to this basaltic soda lake environment. Diversity analyses demonstrate greater diversity and evenness of bacterial species compared to a skewed representation of species for Archaea.     

Use of tissue Doppler imaging to guide tube current modulation in cardiac multidetector computed tomographic angiography

In multidetector computed tomographic coronary angiography, strategies to minimize effective radiation dose (ERD) are urgently needed. Prospective tube current modulation (TCM) allows a decrease in ERD, although it may limit reconstruction options. We sought to determine if tissue Doppler imaging (TDI) by echocardiography could predict an optimal phase for multidetector computed tomography and be used to guide TCM. Echocardiographic studies were performed in 94 patients immediately before multidetector computed tomography (83% men; mean 60 +/- 11 years of age, mean body mass index 27.7+/-4.1 kg/m2) and identified the most quiescent phase of the cardiac cycle within the atrioventricular groove. In 40 patients, prospective TCM was programmed according to TDI (TCM(TDI) group); 54 patients underwent multidetector computed tomography without TCM (no-TCM). In 25 patients assigned to the TCM(TDI) group, multidetector computed tomograms were correlated with invasive quantitative coronary angiograms to ensure maintenance of diagnostic accuracy. Optimal phase determined by TDI was 71 +/- 11%, with a distinct bi-modal distribution. Compared with no-TCM, effective radiation dose was decreased by 42% in the TCM(TDI) group (6.6 +/- 1.2 vs 11.4 +/- 2.2 mSv, p < 0.0001). Only 8 segments (3%) were unevaluable due to motion artifact. In 296 segments, sensitivity, specificity, and positive and negative predictive values to detect lesions > 50% by multidetector computed tomography were 92%, 94%, 65%, and 99%, respectively. There was good correlation between quantitative coronary angiography and multidetector computed tomography for absolute degree of stenosis (r = 0.70, p < 0.0001). In conclusion, TDI is a useful tool to guide prospective TCM in multidetector computed tomography. ERD in multidetector computed tomography may be significantly decreased using this technique while maintaining excellent image quality.     

MRI of the heart: promises fulfilled?

Cardiac magnetic resonance imaging (MRI) has established itself as an important noninvasive method of evaluating a wide array of cardiovascular diseases. Despite these successes, questions remain about whether cardiac MRI is the best way to evaluate patients with complex cardiac conditions in whom more traditional diagnostic techniques have been inconclusive. We review the most important current applications of MRI in heart failure, ischemic heart disease, and myocardial disease.     

Valgus knee injuries: evaluation and documentation using a simple technique of stress radiography

Clinical assessment of post traumatic ligament laxity is subjective. Stress radiographs provide an objective and permanent record of the laxity. We describe a simple method of stress radiography to help evaluate and to document valgus knee injuries. In this study we have correlated the X-ray findings with those at arthroscopy. No specialised equipment is required and radiation exposure to the patient and the surgeon is minimal. With the patient under general anaesthesia the injured and the normal knee are firmly bound together. A valgus stress is applied to both the knees simultaneously and a radiograph is taken. The opening of the medial joint space is measured as in the figure 1, i.e. the perpendicular distance between the tangent drawn to the subchondral bone of the femoral condyles, and the most medial point of the tibial plateau. The opening of the medial joint space provides a direct measure of valgus laxity. The ratio of the medial joint opening to the normal knee is calculated. A ratio of two or more is indicative of an associated anterior or posterior cruciate ligament rupture in addition to medial collateral ligament injury.