Combination Therapy with a Bispecific Antibody Targeting the hERG1/β1 Integrin Complex and Gemcitabine in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) represents an unmet medical need. Difficult/late diagnosis as well as the poor efficacy and high toxicity of chemotherapeutic drugs result in dismal prognosis. With the aim of improving the treatment outcome of PDAC, we tested the effect of combining Gemcitabine with a novel single chain bispecific antibody (scDb) targeting the cancer-specific hERG1/β1 integrin complex.

Ten-year retrospective cohort analysis of ventricular assist device infections.

Background: The number of patients treated by ventricular assist devices (VAD) and the duration of VAD treatment is increasing. One of the main complications in terms of morbidity and mortality for VAD patients are microbial infections. With this study, we aimed to investigate the epidemiology and microbiological characteristics of infections occurring in a VAD population to identify modifiable factors.

Third-generation continuous-flow left ventricular assist devices: a comparative outcome analysis by device type.

Aims: Continuous-flow left ventricular assist devices (CF-LVADs) have become a standard of care in end-stage heart failure. Limited data exist comparing outcomes of HeartMate3 (HM3) and HeartWare HVAD (HW). We aimed to compare midterm outcomes of these devices.

Pump thrombosis and dynamic outflow graft compression: complications in left ventricular assist device therapy.

Over the past decade, left ventricular assist device (VAD) therapy has become more prevalent and increasingly safe. Severe complications, such as VAD pump thrombosis and outflow graft obstruction, are rare, yet still associated with high morbidity and mortality. Clinical presentation, VAD alarm and log files, laboratory analysis, and non-invasive cardiac imaging are crucial for establishing the correct diagnosis and determining clinical management.

Intractable coronary fibromuscular dysplasia leading to end-stage heart failure and fatal heart transplantation.

Coronary fibromuscular dysplasia is uncommon, and even rarer its unstable and recurrent course. We present the unique case of a 52-year-old woman who underwent in total 12 coronary angiographies and three percutaneous coronary intervention within 24 months because of repetitive acute coronary syndromes due to refractory spasm, dissection, restenosis all leading to end-stage heart failure, and heart transplantation. The patient died 12 days after the heart transplantation complicated by intraoperative acute thrombotic occlusion of left anterior descending artery of the graft despite normal pretransplant coronary angiography.

Is it safe to irradiate the newest generation of ventricular assist devices? A case report and systematic literature review.

An increasing number of mechanical assist devices, especially left ventricular assist devices (VADs), are being implanted for prolonged periods and as destination therapy. Some VAD patients require radiotherapy due to concomitant oncologic morbidities, including thoracic malignancies. This raises the potential of VAD malfunction via radiation-induced damage.

[Pharmacological therapy of heart failure with reduced ejection fraction].

Pharmacological therapy of heart failure with reduced ejection fraction Abstract. Pharmacological therapy for heart failure has made great progress over the last three decades and evidence-based therapies have significantly improved survival and quality of life. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and beta-blockers are the cornerstone of the heart failure therapy; indicated in virtually every patient with heart failure and reduced ejection fraction.

Failing Systemic Right Ventricles With Persistent Pulmonary Hypertension: Candidates for Ventricular Assist Devices as Destination Therapy?

Dysfunction of the systemic right ventricle is common after the atrial switch procedure for transposition of the great arteries. Cardiac transplantation remains the only long-term solution in terminal systemic right ventricular (RV) failure, but concomitant pulmonary hypertension (PHT) may preclude it. The increasing number of such patients, together with the concerns related to combined heart-lung transplantation (HLTx), urge us to consider other therapeutic options.

[Ventricular assist device – Possibilities of long-term mechanical circulatory support].

In Switzerland 200’000 people suffer from congestive heart failure. Approximately 10’000 patients find themselves in an advanced state of the disease. When conservative treatment options are no longer available heart transplantation is the therapy of choice.

Continuous flow left ventricular assist devices: a valid option for heart failure patients.

Recent outstanding clinical advances with new mechanical circulatory systems (MCS) have led to additional strategies in the treatment of end stage heart failure (HF). Heart transplantation (HTx) can be postponed and for certain patients even replaced by smaller implantable left ventricular assist devices (LVAD). Mechanical support of the failing left ventricle enables appropriate hemodynamic stabilisation and recovery of secondary organ failure, often seen in these severely ill patients.

[Advanced heart failure - treatment options beyond medical management].

Improvement of heart failure therapy has led to a far better survival and quality of life of patients. Treatment of the underlying disease, patient education and improvement of compliance and consequent upgrading of medical heart failure therapy often delays further progression to an advanced stage of heart failure. Nevertheless heart failure remains a chronic progressive disease and it is up to the treating clinician to identify the signs of advanced heart failure in a timely manner in order to evaluate patients for further treatment strategies such as heart transplantation.

Analysis of single Monte Carlo methods for prediction of reflectance from turbid media.

Starting from the radiative transport equation we derive the scaling relationships that enable a single Monte Carlo (MC) simulation to predict the spatially- and temporally-resolved reflectance from homogeneous semi-infinite media with arbitrary scattering and absorption coefficients. This derivation shows that a rigorous application of this single Monte Carlo (sMC) approach requires the rescaling to be done individually for each photon biography. We examine the accuracy of the sMC method when processing simulations on an individual photon basis and also demonstrate the use of adaptive binning and interpolation using non-uniform rational B-splines (NURBS) to achieve order of magnitude reductions in the relative error as compared to the use of uniform binning and linear interpolation.

Clinical use of temporary percutaneous left ventricular assist devices.

Background: Temporary percutaneous left ventricular assist devices (TPLVAD) can be inserted and removed in awake patients. They substitute left ventricular function for a period of up to a few weeks and provide an excellent backup and bridge to recovery or decision.

Methods: Retrospective analysis of 75 patients who received TPLVAD to treat cardiogenic shock (n = 49) or to facilitate high-risk percutaneous coronary intervention (PCI) (n = 26).

Tailored total lymphoid irradiation in heart transplant patients: 10-years experience of one center.

Background: To assess safety and efficacy of tailored total lymphoid irradiation (tTLI) in cardiac transplant patients.

Methods: A total of seven patients, of which five had recalcitrant cellular cardiac allograft rejection (RCCAR), confirmed by endomyocardial biopsies, and two had side effects of immunosuppressive drug therapy, were all treated with tTLI. tTLI was defined by the adjustment of both the fraction interval and the final irradiation dosage both being dependent on the patients general condition, irradiation-dependent response, and the white blood and platelet counts.

Heart rate response determines long term exercise capacity after heart transplantation.

Background: Exercise capacity after heart transplantation (HTx) remains limited despite normal left ventricular systolic function of the allograft. Various clinical and haemodynamic parameters are predictive of exercise capacity following HTx. However, the predictive significance of chronotropic competence has not been demonstrated unequivocally despite its immediate relevance for cardiac output.

Plasma homocysteine and cardiovascular risk in heart failure with and without cardiorenal syndrome.

Introduction: Plasma homocysteine (Hcy) has been associated with an increased cardiovascular (CV) risk in patients with chronic heart failure (CHF). Thus, we investigated whether Hcy has a prognostic impact on CV events in CHF-patients with and without cardiorenal syndrome (CRS).

Methods: 161 patients with CHF were included in the present analysis.

In vivo measurement of vascular modulation in experimental tumors using a fluorescent contrast agent.

We compared the effectiveness of three optical techniques based on fluorescence imaging and spectroscopy with indocyanine green (ICG) contrast agent to evaluate in vivo the disruption of the active vasculature induced by a vascular targeting agent. The blood perfusion of the MDA-MB-435 tumor model transplanted in nude mice was estimated from the signal of the contrast agent measured immediately after its systemic injection in mice. Optical measurements were performed using a fluorescence imaging setup and a fiber-based time correlated single photon counting (TCSPC) apparatus.

Anthropometric measures and risk of cutaneous malignant melanoma: a case-control study from Italy.

Several studies have investigated the effect of various anthropometric factors on the risk of cutaneous malignant melanoma (CMM). As the results are controversial, we analysed this issue in a case-control study conducted in Italy. The roles of several body size measures were investigated in a hospital-based case-control study of CMM conducted in Italy.

Potential antagonism of tubulin-binding anticancer agents in combination therapies.

ZD6126 is a vascular targeting agent, developed for the treatment of solid tumors. In vivo, ZD6126 is rapidly converted into the tubulin-binding agent N-acetylcolchinol. We have previously reported that in vitro N-acetylcolchinol disrupts microtubules and induces rapid changes in endothelial cell morphology, which in a tumor would lead to a rapid loss of tumor vessel integrity and subsequent extensive tumor necrosis.

A splicing mutation in the alpha/beta GlcNAc-1-phosphotransferase gene results in an adult onset form of mucolipidosis III associated with sensory neuropathy and cardiomyopathy.

A 47-year-old female who presented with a dilated cardiomyopathy and mild neuropathy was found to have pseudoHurler polydystrophy (mucolipidosis III). The serum lysosomal enzymes were strikingly elevated and GlcNAc-1-phosphotransferase activity in the patient's fibroblasts was 3% of normal. Sequence analysis of the patient's genomic DNA revealed a homozygous mutation of the last nucleotide of the 135-bp exon 7 of the phosphotransferase gene encoding the alpha/beta subunits, resulting in aberrant splicing and skipping of this exon.

Vascular-targeting activity of ZD6126, a novel tubulin-binding agent.

The tubulin-binding agent ZD6126 is a novel vascular-targeting agent in clinical development for the treatment of solid tumors. In vivo, ZD6126 is rapidly converted into N-acetylcolchinol (ZD6126 phenol). In this study, we have explored the antivascular property of N-acetylcolchinol in vitro and ZD6126 in vivo.