Evaluation of peak pressure gradients in patients after melody valve implantation: a comparison of cardiac catheterization and doppler echocardiography.

OBJECTIVES: The aim of this study was to determine and quantify the relationship between Doppler echocardiography and cardiac catheterization measurements of the peak right ventricle-pulmonary artery (RV-PA) pressure gradient in patients within 24 hours of Melody valve implantation for treatment of a dysfunctional RV outflow tract (RVOT) conduit or bioprosthetic valve (BPV). BACKGROUND: Patients with a dysfunctional RVOT conduit or BPV are now routinely treated percutaneously with implantation of a Melody valve. However, often the postimplantation catheter measurements of the RV-PA peak gradient do not match the postimplant echo-derived gradients obtained after completion of the procedure. Importantly, these echo gradients are commonly used to monitor patients after implantation over time. METHODS: Medical records of 42 patients with Melody valve implantation were reviewed (men: 25/42; mean age: 22.4 ± 11.2 years; RVOT conduit: 23/42; BPV: 18/42; pulmonic stenosis: 6/42, pulmonic regurgitation: 3/42, both: 33/42). RESULTS: The postimplantation RV-PA peak gradient measured by Doppler echocardiography (within 24 hours of valve implantation) was significantly higher than the measurements acquired by catheterization immediately following implantation (24.2 ± 16.3 mmHg vs. 11.6 ± 8.5 mmHg, P < 0.0001). The relationship showed a moderate-strong correlation (r = 0.65, P < 0.0001) with regression analysis suggesting a linear association in both directions (echo gradient = 1.24 × cath gradient + 9.8, P<0.0001 vs. cath gradient = 0.34 × echo gradient + 3.4, P<0.0001). CONCLUSION: The Doppler echocardiography-derived RV-PA peak gradient within 24 hours of valve implantation is predictably higher than the catheter measured peak gradient immediately following valve implantation. A regression equation was derived to define this important relationship.

Antitumor effects of the investigational selective MEK inhibitor TAK733 against cutaneous and uveal melanoma cell lines.

BACKGROUND: TAK733 is a novel allosteric, non-ATP-binding, inhibitor of the BRAF substrates MEK-1/2. METHODS: The growth inhibitory effects of TAK733 were assessed in a panel of 27 cutaneous and five uveal melanoma cell lines genotyped for driver oncogenic mutations. Flow cytometry, Western blots and metabolic tracer uptake assays were used to characterize the changes induced by exposure to TAK733. RESULTS: Fourteen cutaneous melanoma cell lines with different driver mutations were sensitive to the antiproliferative effects of TAK733, with a higher proportion of BRAFV600E mutant cell lines being highly sensitive with IC50s below 1 nM. The five uveal melanoma cell lines had GNAQ or GNA11 mutations and were either moderately or highly sensitive to TAK733. The tested cell lines wild type for NRAS, BRAF, GNAQ and GNA11 driver mutations were moderately to highly resistant to TAK733. TAK733 led to a decrease in pERK and G1 arrest in most of these melanoma cell lines regardless of their origin, driver oncogenic mutations and in vitro sensitivity to TAK733. MEK inhibition resulted in increase in pMEK more prominently in NRASQ61L mutant and GNAQ mutant cell lines than in BRAFV600E mutant cell lines. Uptake of the metabolic tracers FDG and FLT was inhibited by TAK733 in a manner that closely paralleled the in vitro sensitivity assays. CONCLUSIONS: The MEK inhibitor TAK733 has antitumor properties in melanoma cell lines with different oncogenic mutations and these effects could be detectable by differential metabolic tracer uptake.

Continuing Education for Prehospital Healthcare Providers in India - A Novel Course and Concept.

BACKGROUND: Emergency medical services (EMS) in India face enormous challenges in providing care to a geographically expansive and diverse patient population. Over the last decade, the public-private-partnership GVK EMRI (Emergency Management and Research Institute) has trained over 100,000 emergency medical technicians (EMTs), with greater than 21,000 currently practicing, to address this critical gap in the healthcare workforce. With the rapid development and expansion of EMS, certain aspects of specialty development have lagged behind, including continuing education requirements. To date, there have been no substantial continuing education EMT skills and training efforts. We report lessons learned during development and implementation of a continuing education course (CEC) for EMTs in India. METHODS: From 2014 to 2017, we employed an iterative process to design and launch a novel CEC focused on five core emergency competency areas (medicine and cardiology, obstetrics, trauma, pediatrics, and leadership and communication). Indian EMT instructors and providers partnered in design and content, and instructors were trained to independently deliver the CEC. Many challenges had to be overcome: scale (>21,000 EMTs), standardization (highly variable skill levels among providers and instructors), culture (educational emphasis on rote memorization rather than practical application), and translation (22 major languages and a few hundred local dialects spoken nationwide). LESSONS LEARNED: During the assessment and development phases, we identified five key strategies for success: (1) use icon-based video instruction to ensure consistent quality and allow voice-over for easy translation; (2) incorporate workbooks during didactic videos and (3) employ low-cost simulation and case discussions to emphasize active learning; (4) focus on non-technical skills; (5) integrate a formal training-of-trainers prior to delivery of materials. CONCLUSION: These key strategies can be combined with innovation and flexibility to address unique challenges of language, system resources, and cultural differences when developing impactful continuing educational initiatives in bourgeoning prehospital care systems in low- and middle-income countries.

Adult Epiglottitis: A Case Series.

INTRODUCTION: Emergency Departments are inundated by patients with respiratory illness during the winter months. Emergency physicians are required to quickly identify critically ill patients among the large volume of patients with mild upper respiratory illness. Among these life-threatening conditions is acute epiglottitis. CASE PRESENTATION: We report a rare series of four adult patients who presented to our Emergency Department during a period of only one week in April 2015 and were ultimately diagnosed with acute epiglottitis. Three of the patients improved with conservative measures and were observed in the intensive care unit. One patient required an emergent tracheostomy. DISCUSSION: This series of patients is unique in that all four patients presented to a single Emergency Department within a few days of each other and, despite a myriad of presenting chief complaints, the patients were eventually found to have the same potentially life-threatening diagnosis.These cases reinforce the variability of presenting symptoms and physical examination findings that can occur in patients with epiglottitis. They also highlight clinical findings and adjunctive testing that can help identify patients who would most benefit from intervention.

Spontaneous pneumomediastinum on bedside ultrasound: case report and review of the literature.

Spontaneous pneumomediastinum is a rare disease process with no clear etiology, although it is thought to be related to changes in intrathoracic pressure causing chest pain and dyspnea. We present a case of a 17-year-old male with acute chest pain evaluated initially by bedside ultrasound, which showed normal lung sliding but poor visualization of the parasternal and apical cardiac views due to significant air artifact, representing air in the thoracic cavity. The diagnosis was later verified by chest radiograph. We present a case report on ultrasound-diagnosed pneumomediastinum, and we review the diagnostic modalities to date.