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Apomorphine, used to treat OFF episodes in patients with Parkinson's disease (PD), is typically administered via subcutaneous injections. Administration of an oromucosal solution could offer a non-invasive and user-friendly alternative. This two-part clinical study evaluated the safety, tolerability, pharmacokinetics (PK), and dose proportionality of a novel apomorphine hydrochloride oromucosal solution, as well as its relative bioavailability to subcutaneous apomorphine injection and apomorphine sublingual film. In part A of the study, 12 patients with PD received 2 mg oromucosal apomorphine (4% weight/volume) and 2 mg subcutaneous apomorphine in a randomized order, followed by 4 and 8 mg oromucosal apomorphine. In part B of the study, 13 patients with PD received 7 mg oromucosal apomorphine (7% weight/volume) and 30 mg sublingual apomorphine in a randomized order, followed by 14 mg oromucosal apomorphine. Washout between dose administrations in both study parts was at least 2 days. Safety, tolerability, and PK were assessed pre- and post-dose. Both study parts showed that oromucosal apomorphine was generally well-tolerated. Observed side effects were typical for apomorphine administration and included asymptomatic orthostatic hypotension, yawning, fatigue, and somnolence. Oromucosal apomorphine exposure increased with dose, although less than dose proportional. The mean (SD) maximum exposure reached with 14 mg oromucosal apomorphine was 753.0 (298.6) ng*min/mL (area under the plasma concentration-time curve from zero to infinity) and 8.0 (3.3) ng/mL (maximum plasma concentration). This was comparable to exposure reached after 2 mg subcutaneous apomorphine and approximately half of the exposure observed with 30 mg sublingual apomorphine. In summary, clinically relevant plasma concentrations could be reached in PD patients without tolerability issues., (© 2024 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Objectives: Right heart failure (RHF) is an important prognostic factor in continuous-flow left ventricular assist device (LVAD) therapy. We aimed to assess the clinical variables associated with RHF after LVAD implantation and to compare their performance against currently available RHF predictive scoring systems., Methods: The study cohort comprised 57 patients who underwent LVAD therapy between January 2012 and May 2018 in our centre. The mean age of the patients was 39.9 ± 18.3 years, and 43 (81.1%) of them were men. Thirty-eight patients (66.6%) were in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile I or II. The study cohort was divided into the patients with RHF postoperatively (n = 20, 35.1%) and without RHF (n = 37, 64.9%)., Results: Independent predictors for RHF were preoperative right ventricular ejection fraction <25% [odds ratio (OR) 4.68, 95% confidence interval (CI) 1.41-15.5; P = 0.01], right ventricular stroke work index <400 mmHg ml-1 (OR 3.73, 95% CI 1.01-13.7; P = 0.04), right ventricular outflow tract systolic excursion <7 mm (OR 1.55, 95% CI 0.31-0.84; P = 0.002), right ventricular outflow tract fractional shortening <15% (OR 1.62, 95% CI 0.34-0.78; P = 0.02), right ventricular free wall longitudinal strain ≤19% (OR 3.13, 95% CI 1.01-2.43; P = 0.003), right ventricular fractional area change <27% (OR 3.71, 95% CI 1.15-11.9; P = 0.02) and prealbumin <14 mg/dl (OR 3.45, 95% CI 1.07-11.03; P = 0.03). Modest diagnostic performance for RHF was detected in 4 of 7 validated scoring systems with resulting area under the curve values of 0.70 (95% CI 0.55-0.84; P = 0.001) for the Seattle Heart Failure Model; 0.68 (95% CI 0.49-0.81, P = 0.03) for the Fitzpatrick's; 0.68 (95% CI 0.53-0.83, P = 0.028) for the acute physiology and chronic health evaluation (APACHE) II; and 0.66 (95% CI 0.50-0.82, P = 0.04) for the model for end-stage liver disease scoring systems. However, we found best discrimination performance of the score with a resulting area under the curve value of 0.94 (95% CI 0.55-0.89, P = 0.03) for right ventricular free wall longitudinal strain ≥-15.5% and 0.82 for right ventricular stroke work index <400 mmHg ml-1 m-2 in predicting RHF., Conclusions: Right ventricular free wall longitudinal strain ≥-15.5% and right ventricular stroke work index <400 mmHg ml-1 m-2 were independent predictors of RHF following LVAD implantation. Currently available prediction risk scores had the modest power of accuracy in the low INTERMACS profile Turkish population., (© The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Sutureless aortic valve replacement (SU-AVR) is an alternative technique to standard aortic valve replacement. We evaluated our experience with the Perceval SU-AVR with concomitant mitral valve surgery, with or without tricuspid valve surgery, and aimed to discuss the technical considerations., Methods: From January 2013 through June 2016, 30 patients with concomitant severe mitral valve disease, with or without tricuspid valve disease, underwent SU-AVR with the Perceval prosthesis in a single center., Results: The mean age was 73.0 ± 6.6 years, ranging from 63 to 86 years, and 60% (n = 18) were male. Mean logistic EuroScore of the study cohort was 9.8 ± 4.6. Concomitant procedures consisted of mitral valve repair (n = 8, 26.6%), mitral valve replacement (n = 22, 73.3%), tricuspid valve repair (n = 18, 60%), tricuspid valve replacement (n = 2, 6.6%), and cryoablation for atrial fibrillation (n = 21, 70%). Median prosthesis size was 25 mm (large size). At 1 year, there were 2 deaths from noncardiac causes. One patient (3.3%) had third-degree atrioventricular block requiring permanent pacemaker implantation. Three patients (10%) had intraoperative supra-annular malpositioning of the aortic prosthesis, which was safely removed and reimplanted in all cases. Mean follow-up was 18 ± 4.5 for months (maximum 3 years). During the postoperative period, sinus rhythm restoration rate in patients who underwent the cryo-maze procedure was 76.1% (n = 16) at discharge. There was no structural valve deterioration or migration of the prosthesis at follow-up., Conclusions: Perceval SU-AVR is a technically feasible and safe procedure in patients with severe aortic stenosis with good results even in the presence of multivalvular disease and atrial fibrillation surgery., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Liver resection for intrahepatic cholangiocarcinoma (ICC) with invasion of the inferior vena cava (IVC) and hepatic veins (HV) is a challenging procedure., Case Presentation: We report a case of a 63-year-old woman with a 6-cm, centrally located liver mass. Her biochemistry results were normal except for a Ca19-9 level of 1199 U/ml. The liver biopsy was consistent with ICC and 60% macrosteatosis. Abdominal CT scans revealed a large central mass invading the left HV, middle HV and right HV, infringing on their junction with the vena cava. An operation was planned using a 3-dimensional (3D) computer simulation model using dedicated software. We also describe a novel veno-portal-venous extracorporeal membrane oxygenation (VPV-ECMO) support with in-situ hypothermic perfusion (IHP) during this procedure. We aimed to perform an extended left hepatectomy and reconstruct 3 right HV orifices with an interposition jump graft to the IVC with total vascular exclusion (TVE) and IHP A supplemental video describing the preoperative planning, the operative procedure with the postoperative follow-up in detail is presented. After the patient was discharged, she developed a hepatic venous outflow obstruction 3 months postoperatively, which was effectively managed with hepatic venous stenting by interventional radiology. She is currently symptom free and without tumour recurrence at the 1-year follow-up., Conclusions: This report demonstrates that extended left hepatectomy for IHC with IHP and VPV-ECMO is safe and feasible under the supervision of a highly experienced team.

Objectives: Patients on venoarterial or venovenous extracorporeal membrane oxygenation (ECMO) support may require venoarterial-venous (VAV-ECMO) configuration during follow-up. We report 12 cases of VAV-ECMO with significant outflow steal., Methods: Between October 2014 and November 2016, a total of 97 patients (56.6 ± 12.0 years; 59 men/38 women; body surface area 1.84 ± 0.36 m2) were supported with venoarterial ECMO (n = 85) or venovenous ECMO (n = 12). Among the 97 patients, 12 patients (age 61.5 ± 3.5 years; 8 men/4 women; body surface area 1.8 ± 0.8 m2) required hybrid use of VAV-ECMO. Control and monitoring of flow ratios in supplying cannulae using flow sensors were performed, and occluder devices were used according to patient requirements to achieve optimum haemodynamics and oxygenation., Results: Among the 85 venoarterial ECMO-supported patients, Harlequin syndrome was detected in 9 cases (10.6%) who required switching to VAV-ECMO. Among the 12 patients, 3 (25%) patients required VAV-ECMO while on venovenous ECMO support as a result of initial respiratory failure subsequently developed cardiac decompensation. Mean duration of VAV-ECMO support was 6.4 ± 1.8 days. Overall, on VAV-ECMO support, 70.0 ± 4.6% of blood flow was detected within the supplying right internal jugular vein cannula as a result of lower afterload in venous system. We partially occluded the internal jugular vein cannula and directed flow to the common femoral artery. After adjustment, 34.3 ± 7.4% flow was directed to internal jugular vein and 65.6 ± 7.4% to common femoral artery., Conclusions: Non-invasive monitoring of flow rates within the supplying cannulae of VAV-ECMO and the use of partial occlusion for venous-supplying cannula enable individualized patient management and effective weaning from VAV-ECMO., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Introduction and Objective: We investigated the relationship between coronary sinus (CS) diameter and pulmonary artery systolic pressure (PASP) in patients with pulmonary hypertension (PH) and normal left ventricular systolic function., Methods: A total of 155 participants referred for transthoracic echocardiography were included in the study. The study population consisted of 100 patients with chronic PH and 55 control subjects. Patients with PH were divided into two groups according to PASP: those with PASP 36-45 mmHg, the mild PH group (n=53); and those with PASP >45 mmHg, the moderate to severe PH group (n=47). CS diameter was measured from the posterior atrioventricular groove in apical 4-chamber view during ventricular systole according to the formula: mean CS=(proximal CS+mid CS+distal CS)/3., Results: Mean CS diameter was significantly higher in the moderate to severe PH group than in the controls and in the mild PH group (1.12±0.2 cm vs. 0.82±0.1 cm and 0.87±0.1 cm, respectively; p<0.001). It was significantly correlated with right atrial (RA) area (r=0.674, p<0.001), RA pressure (r=0.458, p<0.001), PASP (r=0.562, p<0.001), inferior vena cava diameter (r=0.416, p<0.001), right ventricular E/A ratio (r=-0.290, p<0.001), and E/Em ratio (r=0.235, p=0.004). RA area (β=0.475, p<0.001) and PASP (β=0.360, p=0.002) were found to be independent predictors of CS diameter., Conclusions: A dilated CS was associated with moderate to severe pulmonary hypertension, and RA area and PASP were independent predictors of CS diameter., (Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.)

Introduction: Cardiac syndrome X (CSX) is a clinical entity defined as the triad of typical angina pectoris on exercise, electrocardiographic or metabolic findings of ischemia and normal epicardial coronary arteries. Platelets, whose amount in the blood is indicated with plateletcrit (PCT), play an important role in inflammatory and thrombotic processes and the physiopathology of cardiovascular events., Aim: To investigate the association between cardiac syndrome X and PCT and platelet count., Material and Methods: A total of 113 patients with normal coronary angiogram were included in the study. Fifty patients with typical chest pain and evidence of myocardial ischemia in non-invasive tests formed the CSX patient group. The control group consisted of 63 age- and gender-matched patients with normal coronary arteries but without angina., Results: The mean PCT value of the CSX group was significantly higher than that of the control group (0.22 ±0.06 vs. 0.19 ±0.04; respectively, p=0.03). Higher PCT was found to be associated with the presence of CSX in patients with normal coronary arteries by multivariate logistic regression analysis., Conclusions: We suggest that high PCT may predict the presence of cardiac syndrome X in patients with normal coronary arteries. The value of PCT appears additive to conventional expensive methods commonly used in CSX prediction.

Behcet's disease (BD) is a multisystemic inflammatory disorder of unknown origin, presenting with mucocutaneous, ocular, articular, vascular, gastrointestinal and central nervous system manifestations. Coronary involvement is very rare in patients with BD. Sildenafil, an oral drug used to treat erectile dysfunction, was shown to cause significant cardiovascular problems including acute myocardial infarction (MI) and sudden cardiac death. Acute MI associated with BD and sildenafil has not been reported previously. We present a case of a 23-year-old male patient with an acute inferior MI associated with BD diagnosed after admission of sildenafil, who was successfully treated with thrombus aspiration and tirofiban administration.

Among all myxomas, left ventricular outflow tract (LVOT) myxomas are very rare. This article reports an LVOT myxoma in a 67-year-old woman presenting with palpitations and weight loss. Surgical excision of the LVOT myxoma was performed.

Aims. The aim of this study was to investigate the relationship of echocardiographic epicardial fat thickness (EFT) with carotid intima-media thickness (CIMT), in patients with type 2 diabetes mellitus (T2DM). Methods and Results. A total of 139 patients with T2DM (mean age 54.3 ± 9.2 and 49.6% male) and 40 age and sex-matched control subjects were evaluated. Echocardiographic EFT and ultrasonographic CIMT were measured in all subjects. Patients with T2DM had significantly increased EFT and CIMT than those of the controls (6.0 ± 1.5 mm versus 4.42 ± 1.0 mm, P < 0.001 and 0.76 ± 0.17 mm versus 0.57 ± 0.14 mm, P < 0.001, resp.). EFT was correlated with CIMT, waist circumference, BMI, age, duration of T2DM, HbA1c in the type 2 diabetic patients. Linear regression analysis showed that CIMT (β = 3.52, t = 3.72, P < 0.001) and waist circumference (β = 0.36, t = 2.26, P = 0.03) were found to be independent predictors of EFT. A cutoff high risk EFT value of 6.3 mm showed a sensitivity and specificity of 72.5% and 71.7%, respectively, for the prediction of subclinical atherosclerosis. Conclusion. We found that echocardiographic EFT was significantly higher in patients with T2DM. Our study also showed that EFT was strongly correlated with waist circumference and CIMT as being independent of sex.

Coronary artery anomalies are not uncommon. The importance of coronary anomalies varies from unimportant to life threatening. Herein, we report for the first time twin circumflex coronary arteries originating separately from the left sinus of Valsalva.

A high diastereoselectivity (up to >99:1) is found for the aziridinations of chiral allylic alcohols with acetoxyaminoquinazolinone (Q-NHOAc). The selectivity is explained in terms of hydrogen bonding between the hydroxy functionality of the allylic alcohol and the remote carbonyl group of the quinazolinone.