Does infection predispose to thrombosis during long-term ventricular assist device support?

Background: Infections and thrombotic events remain life-threatening complications in patients with ventricular assist devices (VAD).

Methods: We describe the relationship between both events in our cohort of patients (n = 220) supported with the HeartWare VAD (HVAD). This is a retrospective analysis of patients undergoing HVAD implantation between July 2009 and March 2019 at the Freeman Hospital, Newcastle upon Tyne, United Kingdom.

Markers of Right Ventricular Dysfunction Predict Maximal Exercise Capacity After Left Ventricular Assist Device Implantation.

Although left ventricular assist device (LVAD) improves functional capacity, on average LVAD patients are unable to achieve the aerobic capacity of normal healthy subjects or mild heart failure patients. The aim of this study was to examine if markers of right ventricular (RV) function influence maximal exercise capacity. This was a single-center prospective study that enrolled 20 consecutive HeartWare ventricular assist device patients who were admitted at the Freeman Hospital (Newcastle upon Tyne, United Kingdom) for a heart transplant assessment from August 2017 to October 2018.

Using existing technology better: Improving outcomes with the HeartWare left ventricular assist device.

Background: The HeartWare left ventricular assist device has been in use for over 12 years. We sought to determine how outcomes at our centre have improved over time.

Methods: Review of electronic hospital records at the Freeman Hospital, Newcastle upon Tyne, United Kingdom.

A prospective cohort study of the safety of breast cancer surgery during COVID-19 pandemic in the West of Scotland.

Introduction: In order to minimise the risk of breast cancer patients for COVID-19 infection related morbidity and mortality prioritisation of care has utmost importance since the onset of the pandemic. However, COVID-19 related risk in patients undergoing breast cancer surgery has not been studied yet. We evaluated the safety of breast cancer surgery during COVID-19 pandemic in the West of Scotland region.

Validity of Hemodynamic Monitoring Using Inert Gas Rebreathing Method in Patients With Chronic Heart Failure and Those Implanted With a Left Ventricular Assist Device.

Objective: The present study assessed agreement between resting cardiac output estimated by inert gas rebreathing (IGR) and thermodilution methods in patients with heart failure and those implanted with a left ventricular assist device (LVAD).

Methods And Results: Hemodynamic measurements were obtained in 42 patients, 22 with chronic heart failure and 20 with implanted continuous flow LVAD (34 males, aged 50 ± 11 years). Measurements were performed at rest using thermodilution and IGR methods.

Initial conservative management strategy of HeartWare left ventricular assist device thrombosis with intravenous heparin or bivalirudin.

Introduction And Objectives: Pump thrombosis is a serious left ventricular assist device complication, though there are no guidelines regarding its treatment. The main aim of this study was to describe a strategy of intravenous anticoagulation as the initial treatment in these patients and then to compare intravenous heparin with bivalirudin.

Methods: All consecutive patients who received a HeartWare left ventricular assist device from July 2009 to March 2019 were retrospectively analysed.

Effect of Preoperative Tricuspid and/or Mitral Regurgitation on Development of Late Right-Sided Heart Failure After Insertion of the HeartWare Left Ventricular Assist Device.

Right-sided heart failure (RHF) after left ventricular assist device implantation is a significant cause of morbidity and mortality. Although multiple predictors of early RHF have been described, information on late RHF is scarce. The aim of this study was to identify predictors of late RHF in left ventricular assist device patients.

Left Ventricular Filling Pressures Contribute to Exercise Limitation in Patients with Continuous Flow Left Ventricular Assist Devices.

We sought to determine hemodynamic mechanisms of exercise intolerance in a group of patients with the HeartWare ventricular assist device (VAD) compared to a group of heart failure patients. Twenty VAD and 22 heart failure patients underwent symptom-limited active straight leg raising exercise during right heart catheterization with thermodilution (TD), and upright cycling cardiopulmonary stress testing with cardiac output measurement by inert gas rebreathing (IGR) method. The TD and IGR exercise cardiac indexes were higher in VAD compared with heart failure group (both P < 0.

Neutrophil to Lymphocyte Ratio Is Related to Thrombotic Complications and Survival in Continuous Flow Left Ventricular Assist Devices.

Left ventricular assist devices (LVADs) have become an established treatment for advanced heart failure, although with long-term support these patients are potentially exposed to serious complications. Our purpose was to assess the role of the neutrophil to lymphocyte ratio (NLR) in LVAD complications and to evaluate if higher values of NLR after 4-6 months on LVAD support (NLR 4_6m) are associated with worse prognosis. All consecutive patients who received a HeartWare LVAD (N = 188, age 50 ± 13 years), as bridge to transplant from December 2009 to January 2018 were included.

A population-based audit of surgical practice and outcomes of oncoplastic breast conservations in Scotland - An analysis of 589 patients.

Introduction: Current evidence for oncoplastic breast conservation (OBC) is based on single institutional series. Therefore, we carried out a population-based audit of OBC practice and outcomes in Scotland.

Methods: A predefined database of patients treated with OBC was completed retrospectively in all breast units practicing OBC in Scotland.

Interactions between MAP kinase and oestrogen receptor in human breast cancer.

Purpose: The oestrogen receptor (ERα) may be activated in a ligand-dependent manner, via oestrogen, or in a ligand-independent manner, via signal transduction pathways. Mitogen Activated Protein Kinase (MAPK) is known to directly phosphorylate ERα at serine 118 in a ligand-independent manner. This study investigated the interaction between MAPK and ERα in breast cancer.

Five-year follow-up of participants in a randomised controlled trial showing benefits from exercise for breast cancer survivors during adjuvant treatment. Are there lasting effects?

Purpose: In an earlier randomised controlled trial, we showed that early stage breast cancer patients who received a supervised exercise programme, with discussion of behaviour change techniques, had psychological and functional benefits 6 months after the intervention. The purpose of this study was to determine if benefits observed at 6 months persisted 18 and 60 months later.

Methods: Women who were in the original trial were contacted at 18 and 60 months after intervention.

Sphingosine kinase 1 induces tolerance to human epidermal growth factor receptor 2 and prevents formation of a migratory phenotype in response to sphingosine 1-phosphate in estrogen receptor-positive breast cancer cells.

We demonstrate here a new concept termed "oncogene tolerance" whereby human EGF receptor 2 (HER2) increases sphingosine kinase 1 (SK1) expression in estrogen receptor-positive (ER(+)) MCF-7 HER2 cells and SK1, in turn, limits HER2 expression in a negative-feedback manner. The HER2-dependent increase in SK1 expression also limits p21-activated protein kinase 1 (p65 PAK1) and extracellular signal regulated kinase 1/2 (ERK-1/2) signaling. Sphingosine 1-phosphate signaling via S1P(3) is also altered in MCF-7 HER2 cells.

Is expression or activation of Src kinase associated with cancer-specific survival in ER-, PR- and HER2-negative breast cancer patients?

The aim of the current study was to assess the expression levels of c-Src and phosphorylated Src kinase in human breast cancers and to establish if these are linked to oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status or patient survival. Tissue microarray technology was used to analyze 314 breast cancer specimens. Immunohistochemistry was performed using antibodies to c-Src, Y419Src, and Y215Src, and expression was assessed using the weighted histoscore method.

Ras/Raf-1/MAPK pathway mediates response to tamoxifen but not chemotherapy in breast cancer patients.

Purpose: The expression and activation of the Ras/Raf-1/mitogen-activated protein kinase (MAPK) pathway plays an important role in the development and progression of cancer, and may influence response to treatments such as tamoxifen and chemotherapy. In this study we investigated whether the expression and activation of the key components of this pathway influenced clinical outcome, to test the hypothesis that activation of the MAPK pathway drives resistance to tamoxifen and chemotherapy in women with breast cancer.

Experimental Design: Breast tumors from patients at the Glasgow Royal Infirmary and others treated within the BR9601 trial were analyzed for expression of the three Ras isoforms, total Raf-1, active and inactive forms of Raf-1 [pRaf(ser338) and pRaf(ser259), respectively], MAPK, and phospho-MAPK using an immunohistochemical approach.

Expression of tumor necrosis factor alpha converting enzyme in endocrine cancers.

Tumor necrosis factor alpha converting enzyme (TACE) mediates shedding of human epidermal growth factor receptor-4 (HER4). Recent data suggest that released HER4 intracellular domain (4ICD) induces apoptosis in breast cancer. TACE expression, as measured by immunohistochemical analysis, was observed in 183 of 383 breast carcinomas, 39 of 217 ovarian carcinomas, and 16 of 24 and 17 of 24 hormonesensitive and hormone-insensitive prostate carcinomas, respectively.

Amplified in breast cancer 1 in human epidermal growth factor receptor - positive tumors of tamoxifen-treated breast cancer patients.

Purpose: Amplified in breast cancer 1 (AIB1) is a member of the p160/steroid receptor coactivators family and is involved in estrogen-dependent gene transcription by reducing the antagonistic activity of tamoxifen-bound estrogen receptor-alpha (ER-alpha). The present study was carried out to test the hypothesis that AIB1 protein expression and/or gene amplification mediates tamoxifen resistance in breast cancer.

Experimental Design: Immunohistochemistry using AIB1 antibody and fluorescence in situ hybridization using probes specific for AIB1 and chromosome 20 was done on 402 ER-alpha-positive tamoxifen-treated breast cancers.

Bad expression predicts outcome in patients treated with tamoxifen.

Aims: Activation of the PI3K/Akt signal transduction pathway has been linked to endocrine resistance in tamoxifen treated breast cancer patients. Activation of the PI3K/Akt pathway causes phosphorylation of Bad leading to modulation of cellular apoptosis. The present study was carried out to test the hypothesis that disruption of apoptosis in breast cancer, via Akt activation, is linked with hormone resistance.

The ERBB4/HER4 intracellular domain 4ICD is a BH3-only protein promoting apoptosis of breast cancer cells.

ERBB4/HER4 (referred to here as ERBB4) is a unique member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. In contrast to the other three members of the EGFR family (i.e.

HER4 in breast cancer: comparison of antibodies against intra- and extra-cellular domains of HER4.

Introduction: We have previously linked HER4 expression with increased survival in breast cancer. However, other reports have associated HER4 with adverse prognostic significance. One possible explanation for the conflicting reports may be that these results are antibody dependent.

AKT activation predicts outcome in breast cancer patients treated with tamoxifen.

Oestrogen receptor (ERalpha) expression is a strong predictor of response to endocrine therapy. The PI3K/AKT/mTOR signal transduction pathway has been implicated in endocrine resistance in vitro. The present study was carried out to test the hypothesis that AKT activation mediates tamoxifen resistance in clinical breast cancer.

Can molecular markers predict when to implement treatment with aromatase inhibitors in invasive breast cancer?

Purpose: Resistance to tamoxifen is linked to overexpression of HER2, and aromatase inhibitors show particular benefit in progesterone receptor (PR)-negative patients. We previously reported reduced survival in patients overexpressing HER1, HER2, and HER3. We now show that both HER1-3 and PR status predicts for early relapse in estrogen receptor (ER)-positive tamoxifen-treated breast cancer patients.

Outcome and human epidermal growth factor receptor (HER) 1-4 status in invasive breast carcinomas with proliferation indices evaluated by bromodeoxyuridine labelling.

Background: We have shown previously that whereas overexpression of human epidermal growth factor receptor (HER)1, HER2 and HER3 is associated with poor prognosis in breast cancer, HER4 is associated with a good prognosis. Cell proliferation is a key component of aggressive cancers and is driven by growth factors. In this study, bromodeoxyuridine (BrdU)-derived proliferation indices are correlated with clinical outcome and HER1-4 status for further clarification of the differing roles for the HER family at a biological level.