Risk of adverse outcomes associated with cardiac sarcoidosis diagnostic schemes

BackgroundMultiple cardiac sarcoidosis (CS) diagnostic schemes have been published.ObjectivesThis study aims to evaluate the association of different CS diagnostic schemes with adverse outcomes. The diagnostic schemes evaluated were 1993, 2006, and 2017 Japanese criteria and the 2014 Heart Rhythm Society criteria.MethodsData were collected from the Cardiac Sarcoidosis Consortium, an international registry of CS patients. Outcome events were any of the following: all-cause mortality, left ventricular assist device placement, heart transplantation, and appropriate implantable cardioverter-defibrillator therapy. Logistic regression analysis evaluated the association of outcomes with each CS diagnostic scheme.ResultsA total of 587 subjects met the following criteria: 1993 Japanese (n = 310, 52.8%), 2006 Japanese (n = 312, 53.2%), 2014 Heart Rhythm Society (n = 480, 81.8%), and 2017 Japanese (n = 112, 19.1%). Patients who met the 1993 criteria were more likely to experience an event than patients who did not (n = 109 of 310, 35.2% vs n = 59 of 277, 21.3%; OR: 2.00; 95% CI: 1.38-2.90; P P P = 0.18 or OR: 1.51; 95% CI: 0.97-2.33; P = 0.067, respectively).ConclusionsCS patients who met the 1993 and the 2006 criteria had higher odds of adverse clinical outcomes. Future research is needed to prospectively evaluate existing diagnostic schemes and develop new risk models for this complex disease.Cardiolog

Ajmaline blocks INa and IKr without eliciting differences between Brugada syndrome patient and control human pluripotent stem cell-derived cardiac clusters

© 2017 The Authors The class Ia anti-arrhythmic drug ajmaline is used clinically to unmask latent type I ECG in Brugada syndrome (BrS) patients, although its mode of action is poorly characterised. Our aims were to identify ajmaline's mode of action in human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs), and establish a simple BrS hiPSC platform to test whether differences in ajmaline response could be determined between BrS patients and controls. Control hiPSCs were differentiated into spontaneously contracting cardiac clusters. It was found using multi electrode array (MEA) that ajmaline treatment significantly lengthened cluster activation-recovery interval. Patch clamping of single CMs isolated from clusters revealed that ajmaline can block both I Na and I Kr . Following generation of hiPSC lines from BrS patients (absent of pathogenic SCN5A sodium channel mutations), analysis of hiPSC-CMs from patients and controls revealed that differentiation and action potential parameters were similar. Comparison of cardiac clusters by MEA showed that ajmaline lengthened activation-recovery interval consistently across all lines. We conclude that ajmaline can block both depolarisation and repolarisation of hiPSC-CMs at the cellular level, but that a more refined integrated tissue model may be necessary to elicit differences in its effect between BrS patients and controls

Prognostic significance of FLT3 internal tandem duplication and tyrosine kinase domain mutations in acute promyelocytic leukemia: A systematic review

The fms-like tyrosine kinase 3 (FLT3) gene aberrations, internal tandem duplication (ITD) and tyrosine kinase domain (TKD) mutations, are frequent in acute promyelocytic leukemia (APL). To evaluate their prognostic significance, we performed a systematic review and meta-analysis. Eleven studies covering a total of 1063 subjects were included in this review. Incidence of ITD and TKD mutations was 12–38% and 2–20%, respectively. In 9 of 11 studies, ITD was associated with high WBC count at the time of diagnosis, which is a known prognostic indicator in APL. Patients with ITD had inferior 3-year overall survival compared to patients without ITD (risk ratio 1.42, 95% CI: 1.04–1.95). Similarly, ITD was also associated with adverse 3-year disease-free survival (risk ratio 1.48, 95% CI: 1.02–2.15). There were only two studies that evaluated the association of TKD mutation in APL; both showed a trend towards worse survival in patients with mutated TKD. In conclusion, FLT3 ITD is associated with high WBC at diagnosis in patients with APL. Although the available literature is limited to observational studies, our systematic review suggests that FLT3 mutations, especially ITD, can adversely affect overall survival and disease-free survival in APL

Analysis of water reuse potential for irrigation in Lebanon

Water scarcity and pollution are major threats for human development in the Middle East and North Africa (MENA) region, and Lebanon is no exception. Wastewater treatment and reuse in agriculture can contribute to addressing the increasing water crisis in the MENA region. However, what is the actual potential of water reuse as a solution for agriculture in Lebanon? This report addresses this question and provides the most comprehensive assessment of water reuse potential up to now. Using geographic information system (GIS) modelling and the best and most recent data available in the country, the report develops a detailed technical assessment of the quantities of treated water available for safe reuse in irrigation, and identifies the wastewater treatment plants that have the highest potential for that purpose. The report also examines the governance barriers that need to be overcome for the water reuse potential to materialize in practice. These barriers include structural shortcomings in the wastewater sector combined with challenges of governance and the lack of a regulatory framework for reuse management. Once the current economic, financial and political crisis in Lebanon eases, addressing these barriers will be key to achieving more and safer water reuse in the country

Analysis of water reuse potential for irrigation in Lebanon

Water scarcity and pollution are major threats for human development in the Middle East and North Africa (MENA) region, and Lebanon is no exception. Wastewater treatment and reuse in agriculture can contribute to addressing the increasing water crisis in the MENA region. However, what is the actual potential of water reuse as a solution for agriculture in Lebanon? This report addresses this question and provides the most comprehensive assessment of water reuse potential up to now. Using geographic information system (GIS) modelling and the best and most recent data available in the country, the report develops a detailed technical assessment of the quantities of treated water available for safe reuse in irrigation, and identifies the wastewater treatment plants that have the highest potential for that purpose. The report also examines the governance barriers that need to be overcome for the water reuse potential to materialize in practice. These barriers include structural shortcomings in the wastewater sector combined with challenges of governance and the lack of a regulatory framework for reuse management. Once the current economic, financial and political crisis in Lebanon eases, addressing these barriers will be key to achieving more and safer water reuse in the country

Outcomes of intraoperative ultrasound for endoscopic endonasal transsphenoidal pituitary surgery in adenomas with parasellar extension

Background: Pituitary adenomas with parasellar extension present a technical challenge for adequate visualization and gross total resection (GTR). The endoscope improves identification of parasellar extension, however, additional intraoperative imaging adjuncts can further augment visualization. Intraoperative ultrasound (iUS) may provide a viable and cost-effective solution for intraoperative imaging. We sought to assess the ability of intraoperative ultrasound to predict extent of resection on 3-month postoperative magnetic resonance imaging (MRI) in pituitary adenomas with parasellar extension. Methods: Twenty consecutive patients undergoing endoscopic endonasal transsphenoidal surgery for pituitary adenomas with the assistance of intraoperative ultrasound were prospectively collected. Intraoperative ultrasound findings were recorded during each case. 3-month postoperative MRI studies were reviewed in a blinded fashion to assess for residual tumor and compared with the intraoperative ultrasound findings. Results: Median preoperative Knosp grade was 2. Cavernous sinus invasion was encountered intraoperatively in 3 patients, all of whom were Knosp grade 3 preoperatively. Median operative time was 152 min. Based on iUS findings, 17 patients were expected to have a GTR while 3 patients underwent subtotal resection. 18 patients completed a 3-month postoperative MRI. The iUS and MRI findings were concordant in 16 cases (88.9%) with only two instances of discordance. Conclusion: Intraoperative ultrasound can reliably predict tumor resection as assessed by 3-month postoperative MRI in pituitary adenomas with parasellar extension. Image capture and interpretation may vary based on operator experience. Ultrasound provides reliable immediate assessment of extent of resection, identification of normal pituitary gland and other important neurovascular structures