In vivo fluid dynamics of the Ventura interatrial shunt device in patients with heart failure.

AIMS: Interatrial shunts are under evaluation as a treatment for heart failure (HF); however, their in vivo flow performance has not been quantitatively studied. We aimed to investigate the fluid dynamics properties of the 0.51 cm orifice diameter Ventura shunt and assess its lumen integrity with serial transesophageal echocardiography (TEE). METHODS AND RESULTS: Computational fluid dynamics (CFD) and bench flow tests were used to establish the flow-pressure relationship of the shunt. Open-label patients from the RELIEVE-HF trial underwent TEE at shunt implant and at 6 and 12 month follow-up. Shunt effective diameter (Deff) was derived from the vena contracta, and flow was determined by the continuity equation. CFD and bench studies independently validated that the shunt's discharge coefficient was 0.88 to 0.89. The device was successfully implanted in all 97 enrolled patients; mean age was 70 ± 11 years, 97% were NYHA class III, and 51% had LVEF ≤40%. Patency was confirmed in all instances, except for one stenotic shunt at 6 months. Deff remained unchanged from baseline at 12 months (0.47 ± 0.01 cm, P = 0.376), as did the trans-shunt mean pressure gradient (5.1 ± 3.9 mmHg, P = 0.316) and flow (1137 ± 463 mL/min, P = 0.384). TEE measured flow versus pressure closely correlated (R2 ≥ 0.98) with a fluid dynamics model. At 12 months, the pulmonary/systemic flow Qp/Qs ratio was 1.22 ± 0.12. CONCLUSIONS: When implanted in patients with advanced HF, this small interatrial shunt demonstrated predictable and durable patency and performance.

Orphan disease status of cancer cachexia in the USA and in the European Union: a systematic review.

BACKGROUND: Cachexia has significant impact on the patients' quality of life and prognosis. It is frequently observed in patients with cancer, especially in advanced stages, but prevalence data for the overall population are lacking. Good quality estimates of cancer cachexia in general and for each of the major cancer types would be highly relevant for potential treatment development efforts in this field. Both the USA and European Union (EU) have implemented special clinical development rules for such rare disorders what are called 'orphan diseases'. The cut-off level for a disease to be considered an orphan disease in the USA is 200 000 people (0.06% of the population) and EU is 5 per 10 000 people (0.05% of the population). METHODS: For this systematic review, we searched at PubMed (from inception to 31 January 2018) to identify clinical studies that assessed the prevalence of cachexia in cancer patients at risk. Studies reporting the prevalence of either cancer cachexia or wasting disease in the top-10 cancer types and 4 other selected cancer types known to be particularly commonly complicated by cachexia were included in this analysis (i.e. prostate cancer, breast cancer, colorectal cancer, melanoma, endometrial cancer, thyroid cancer, urinary bladder cancer, non-hodgkin lymphoma, lung cancer, kidney and renal pelvis cancer, head and neck cancer, gastric cancer, liver cancer, and pancreatic cancer). We calculated the current burden of cancer cachexia, disease by disease, in the USA and in the EU and compared them to the current guidelines for the definition of orphan disease status. RESULTS: We estimate that in 2014 in the USA, a total of 527 100 patients (16.5 subjects per 10 000 people of the total population), and in 2013 in the EU, a total of 800 300 patients (15.8 subjects per 10 000 people of the total population) suffered from cancer cachexia (of any kind). In the 14 separately analysed cancer types, the prevalence of cancer cachexia in the USA ranged between 11 300 (0.4/10 000, gastric cancer) and 92 000 patients (2.9/10 000, lung cancer) and in the EU between 14 300 (0.3/10 000, melanoma of the skin) and 150 100 (3.0/10 000, colorectal cancer). CONCLUSIONS: The absolute number of patients affected by cancer cachexia in each cancer group is lower than the defined thresholds for orphan diseases in the USA and EU. Cancer cachexia in each subgroup separately should be considered an orphan disease.

Early Detection of Lung Cancer with Meso Tetra (4-Carboxyphenyl) Porphyrin-Labeled Sputum.

INTRODUCTION: Early detection of lung cancer in high-risk individuals reduces mortality. Low-dose spiral computed tomography (LDCT) is the current standard but suffers from an exceedingly high false-positive rate (>96%) leading to unnecessary and potentially dangerous procedures. We, therefore, set out to develop a simple, noninvasive, and quantitative assay to detect lung cancer. METHODS: This proof-of-concept study evaluated the sensitivity/specificity of the CyPath Early Lung Cancer Detection Assay to correctly classify LDCT-confirmed cohorts of high-risk control (n = 102) and cancer (n = 26) subjects. Fluorescence intensity parameters of red fluorescent cells (RFCs) from tetra (4-carboxyphenyl) porphyrin (TCPP)-labeled lung sputum samples and subjects' baseline characteristics were assessed for their predictive power by multivariable logistic regression. A receiver operating characteristic curve was constructed to evaluate the sensitivity/specificity of the CyPath assay. RESULTS: RFCs were detectable in cancer subjects more often than in high-risk ones (p = 0.015), and their characteristics differed between cohorts. Two independent predictors of cancer were the mean of RFC average fluorescence intensity/area per subject (p < 0.001) and years smoked (p = 0.003). The CyPath-based classifier had an overall accuracy of 81% in the test population; false-positive rate of 40% and negative predictive value of 83%. CONCLUSIONS: The tetra (4-carboxyphenyl) porphyrin -based CyPath assay correctly classified study participants into cancer or high-risk cohorts with considerable accuracy. Optimizing sputum collection, sample reading, and refining the classifier should improve sensitivity and specificity. The CyPath assay thus has the potential to complement LDCT screening or serve as a stand-alone approach for early lung cancer detection.

The REDUCE pivotal trial: a prospective, randomized controlled pivotal trial of a dual intragastric balloon for the treatment of obesity.

BACKGROUND: Saline-filled intragastric balloon devices are reversible endoscopic devices designed to occupy stomach volume and reduce food intake. OBJECTIVE: To evaluate the safety and effectiveness of a dual balloon system plus diet and exercise in the treatment of obesity compared to diet and exercise alone. SETTING: Academic and community practice, United States. METHODS: Participants (n = 326) with body mass index (BMI) 30-40 kg/m(2) were randomized to endoscopic DBS treatment plus diet and exercise (DUO, n = 187) or sham endoscopy plus diet and exercise alone (DIET, n = 139). Co-primary endpoints were a between-group comparison of percent excess weight loss (%EWL) and DUO subject responder rate, both at 24 weeks. Thereafter DUO patients had the DBS retrieved followed by 24 additional weeks of counseling; DIET patients were offered DBS treatment. RESULTS: Mean BMI was 35.4. Both primary endpoints were met. DUO weight loss was over twice that of DIET. DUO patients had significantly greater %EWL at 24 weeks (25.1% intent-to-treat (ITT), 27.9% completed cases (CC, n = 167) compared with DIET patients (11.3% ITT, P = .004, 12.3% CC, n = 126). DUO patients significantly exceeded a 35% response rate (49.1% ITT, P<.001, 54.5% CC) for weight loss dichotomized at 25%EWL. Accommodative symptoms abated rapidly with support and medication. Balloon deflation occurred in 6% without migrations. Early retrieval for nonulcer intolerance occurred in 9%. Gastric ulcers were observed; a minor device change led to significantly reduced ulcer size and frequency (10%). CONCLUSION: The DBS was significantly more effective than diet and exercise in causing weight loss with a low adverse event profile.

Incidence and significance of early recurrences of atrial fibrillation after cryoballoon ablation: insights from the multicenter Sustained Treatment of Paroxysmal Atrial Fibrillation (STOP AF) Trial.

BACKGROUND: Early recurrence of atrial fibrillation (ERAF) is common after radiofrequency catheter ablation for AF. We sought to determine the incidence and prognostic significance of ERAF after cryoballoon ablation. Moreover, the benefit of early reablation for ERAF after cryoballoon ablation is undetermined. METHODS AND RESULTS: The Sustained Treatment of Paroxysmal Atrial Fibrillation (STOP AF) trial randomized 245 patients with paroxysmal AF to medical therapy versus cryoballoon-based pulmonary vein ablation. Patients were followed for 12 months. ERAF was defined as any recurrence of AF >30 seconds during the first 3 months of follow-up. Late recurrence (LR) was defined as any recurrence of AF >30 seconds between 3 and 12 months. Of the 163 patients randomized to cryoablation, 84 patients experienced ERAF (51.5%). The only significant factor associated with ERAF was male sex (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.03-4.61; P=0.041). LR was observed in 41 patients (25.1%), and was significantly related to ERAF (55.6% LR with ERAF versus 12.7% without ERAF; P<0.001). Among patients with ERAF, only current tobacco use (HR, 3.84; 95% CI, 1.82-8.11; P<0.001) was associated with LR. Conversely, early reablation was associated with greater freedom from LR (3.3% LR with early reablation versus 55.6% without; HR, 0.04; 95% CI, 0.01-0.32; P=0.002). CONCLUSIONS: ERAF after cryoballoon ablation occurs in ≈50% of patients and is strongly associated with LR. Early reablation for ERAF is associated with excellent long-term freedom from recurrent AF.

Cryoballoon ablation of pulmonary veins for paroxysmal atrial fibrillation: first results of the North American Arctic Front (STOP AF) pivotal trial.

OBJECTIVES: This study sought to assess the safety and effectiveness of a novel cryoballoon ablation technology designed to achieve single-delivery pulmonary vein (PV) isolation. BACKGROUND: Standard radiofrequency ablation is effective in eliminating atrial fibrillation (AF) but requires multiple lesion delivery at the risk of significant complications. METHODS: Patients with documented symptomatic paroxysmal AF and previously failed therapy with ≥ 1 membrane active antiarrhythmic drug underwent 2:1 randomization to either cryoballoon ablation (n = 163) or drug therapy (n = 82). A 90-day blanking period allowed for optimization of antiarrhythmic drug therapy and reablation if necessary. Effectiveness of the cryoablation procedure versus drug therapy was determined at 12 months. RESULTS: Patients had highly symptomatic AF (78% paroxysmal, 22% early persistent) and experienced failure of at least one antiarrhythmic drug. Cryoablation produced acute isolation of three or more PVs in 98.2% and all four PVs in 97.6% of patients. PVs isolation was achieved with the balloon catheter alone in 83%. At 12 months, treatment success was 69.9% (114 of 163) of cryoblation patients compared with 7.3% of antiarrhythmic drug patients (absolute difference, 62.6% [p < 0.001]). Sixty-five (79%) drug-treated patients crossed over to cryoablation during 12 months of study follow-up due to recurrent, symptomatic AF, constituting drug treatment failure. There were 7 of the resulting 228 cryoablated patients (3.1%) with a >75% reduction in PV area during 12 months of follow-up. Twenty-nine of 259 procedures (11.2%) were associated with phrenic nerve palsy as determined by radiographic screening; 25 of these had resolved by 12 months. Cryoablation patients had significantly improved symptoms at 12 months. CONCLUSIONS: The STOP AF trial demonstrated that cryoballoon ablation is a safe and effective alternative to antiarrhythmic medication for the treatment of patients with symptomatic paroxysmal AF, for whom at least one antiarrhythmic drug has failed, with risks within accepted standards for ablation therapy. (A Clinical Study of the Arctic Front Cryoablation Balloon for the Treatment of Paroxysmal Atrial Fibrillation [Stop AF]; NCT00523978).

Detection of breast cancer with full-field digital mammography and computer-aided detection.

OBJECTIVE: The purpose of this study was to evaluate computer-aided detection (CAD) performance with full-field digital mammography (FFDM). MATERIALS AND METHODS: CAD (Second Look, version 7.2) was used to evaluate 123 cases of breast cancer detected with FFDM (Senographe DS). Retrospectively, CAD sensitivity was assessed using breast density, mammographic presentation, histopathology results, and lesion size. To determine the case-based false-positive rate, patients with four standard views per case were included in the study group. Eighteen unilateral mammography examinations with nonstandard views were excluded, resulting in a sample of 105 bilateral cases. RESULTS: CAD detected 115 (94%) of 123 cancer cases: six of six (100%) in fatty breasts, 63 of 66 (95%) in breasts containing scattered fibroglandular densities, 43 of 46 (93%) in heterogeneously dense breasts, and three of five (60%) in extremely dense breasts. CAD detected 93% (41/44) of cancers manifesting as calcifications, 92% (57/62) as masses, and 100% (17/17) as mixed masses and calcifications. CAD detected 94% of the invasive ductal carcinomas (n = 63), 100% of the invasive lobular carcinomas (n = 7), 91% of the other invasive carcinomas (n = 11), and 93% of the ductal carcinomas in situ (n = 42). CAD sensitivity for cancers 1-10 mm (n = 55) was 89%; 11-20 mm (n = 37), 97%; 21-30 mm (n = 16), 100%; and larger than 30 mm (n = 15), 93%. The CAD false-positive rate was 2.3 marks per four-image case. CONCLUSION: CAD with FFDM showed a high sensitivity in identifying cancers manifesting as calcifications and masses. Sensitivity was maintained in cancers with lower mammographic sensitivity, including invasive lobular carcinomas and small neoplasms (1-20 mm). CAD with FFDM should be effective in assisting radiologists with earlier detection of breast cancer. Future studies are needed to assess CAD accuracy in larger populations.