Evaluating the impact of modeling choices on the performance of integrated genetic and clinical models.

Purpose: The value of genetic information for improving the performance of clinical risk prediction models has yielded variable conclusions. Many methodological decisions have the potential to contribute to differential results. We performed multiple modeling experiments integrating clinical and demographic data from electronic health records (EHR) with genetic data to understand which decisions may affect performance.

Evaluating the impact of modeling choices on the performance of integrated genetic and clinical models.

The value of genetic information for improving the performance of clinical risk prediction models has yielded variable conclusions. Many methodological decisions have the potential to contribute to differential results across studies. Here, we performed multiple modeling experiments integrating clinical and demographic data from electronic health records (EHR) and genetic data to understand which decision points may affect performance.

Patient-specific severity of von Willebrand factor degradation identifies patients with a left ventricular assist device at high risk for bleeding.

Background: Continuous-flow left ventricular assist devices (LVADs) cause an acquired von Willebrand factor (VWF) deficiency and bleeding. Models to risk-stratify for bleeding are urgently needed. We developed a model of continuous-flow LVAD bleeding risk from patient-specific severity of VWF degradation.

Association of Essential Tremor With Novel Risk Loci: A Genome-Wide Association Study and Meta-analysis.

Importance: Essential tremor (ET) is one of the most common movement disorders, affecting 5% of the general population older than 65 years. Common variants are thought to contribute toward susceptibility to ET, but no variants have been robustly identified.

Objective: To identify common genetic factors associated with risk of ET.

Decreased RPM reduces von Willebrand factor degradation with the EVAHEART LVAS: implications for device-specific LVAD management.

Background: Continuous-flow left ventricular assist devices (LVADs) produces supraphysiologic shear stress that causes von Willebrand factor (VWF) degradation and a bleeding diathesis. Reduction of revolutions per minute (RPM) with axial-flow LVADs does not decrease shear stress enough to reduce VWF degradation and bleeding. However, it is unknown if RPM reduction with centrifugal flow LVADs may minimize VWF degradation.

Tinagl1 Suppresses Triple-Negative Breast Cancer Progression and Metastasis by Simultaneously Inhibiting Integrin/FAK and EGFR Signaling.

Triple-negative breast cancer (TNBC) patients have the worst prognosis and distant metastasis-free survival among all major subtypes of breast cancer. The poor clinical outlook is further exacerbated by a lack of effective targeted therapies for TNBC. Here we show that ectopic expression and therapeutic delivery of the secreted protein Tubulointerstitial nephritis antigen-like 1 (Tinagl1) suppresses TNBC progression and metastasis through direct binding to integrin α5β1, αvβ1, and epidermal growth factor receptor (EGFR), and subsequent simultaneous inhibition of focal adhesion kinase (FAK) and EGFR signaling pathways.

Clinical and In Vitro Evidence That Left Ventricular Assist Device-Induced von Willebrand Factor Degradation Alters Angiogenesis.

Background Gastrointestinal bleeding from angiodysplasia is a major problem in continuous-flow left ventricular assist device (LVAD) patients. LVAD shear stress causes pathologic degradation of VWF (von Willebrand factor). A mechanistic relationship between VWF degradation and angiodysplasia has not been explored.

Clinical and In Vitro Evidence That Subclinical Hemolysis Contributes to LVAD Thrombosis.

Background: Recent data suggest that hemolysis contributes to left ventricular assist device (LVAD) thrombosis, but the mechanism is unknown. In a clinical study, we measured plasma free hemoglobin (pfHgb) and the incidence of LVAD thrombosis. In an in vitro study, we examined biophysical relationships between shear stress, pfHgb and von Willebrand factor (vWF) metabolism toward understanding mechanisms of LVAD thrombosis.

Continuous-Flow LVAD Support Causes a Distinct Form of Intestinal Angiodysplasia.

Rationale: The objective of this autopsy study was to determine whether gastrointestinal angiodysplasia develops during continuous-flow left ventricular assist device (LVAD) support.

Objective: LVAD support causes pathologic degradation of von Willebrand factor (vWF) and bleeding from gastrointestinal angiodysplasia at an alarming rate. It has been speculated that LVAD support itself may cause angiodysplasia.

A salt-sensing kinase in T lymphocytes, SGK1, drives hypertension and hypertensive end-organ damage.

We previously showed that angiotensin II (Ang II) increases T cell production of IL-17A, and that mice deficient in IL-17A have blunted hypertension and attenuated renal and vascular dysfunction. It was recently shown that salt enhances IL-17A production from CD4+ T cells via a serum- and glucocorticoid-regulated kinase 1-dependent (SGK1-dependent) pathway. Thus, we tested the hypothesis that SGK1 signaling in T cells promotes hypertension and contributes to end-organ damage.

Left Ventricular Assist Device Design Reduces von Willebrand Factor Degradation: A Comparative Study Between the HeartMate II and the EVAHEART Left Ventricular Assist System.

Background: Supraphysiologic shear stress from continuous-flow left ventricular assist devices (LVADs) accelerates von Willebrand factor (vWF) degradation and predisposes patients to nonsurgical bleeding. It is unknown whether unique design characteristics of LVADs differentially affect vWF degradation. We tested the hypothesis that the centrifugal-flow EVAHEART (Evaheart, Houston, TX) left ventricular assist system (LVAS), which was designed to minimize shear stress (low operational revolutions per minute [rpm], larger flow gaps, low shear stress, flat H-Q curve), reduced vWF degradation versus the axial-flow HeartMate II (Thoratec, Pleasanton, CA) LVAD.

Reduced continuous-flow left ventricular assist device speed does not decrease von Willebrand factor degradation.

Background: Nonsurgical bleeding is a frequent complication of continuous-flow left ventricular assist device (LVAD) support. Abnormal von Willebrand factor (vWF) metabolism plays a major role. However, the relationship between LVAD speed and vWF degradation is unknown.

Continuous glucose monitoring system in the operating room and intensive care unit: any difference according to measurement sites?

Given the benefit of glucose control in the perioperative period, we evaluated the accuracy and performance of the continuous glucose monitoring system (CGMS) depending on different measurement sites in the operating room (OR) and in the intensive care unit (ICU). Patients over 18 years of age scheduled for elective surgery and ICU admission were enrolled prospectively. Two CGMS sensors were inserted into the subcutaneous tissue of the proximal lateral thigh and the lateral abdomen.

Inhibition of ADAMTS-13 by Doxycycline Reduces von Willebrand Factor Degradation During Supraphysiological Shear Stress: Therapeutic Implications for Left Ventricular Assist Device-Associated Bleeding.

Objectives: The aim of this study was to investigate a potential therapy for left ventricular assist device (LVAD)-associated bleeding.

Background: Nonsurgical bleeding is the most frequent complication of LVAD support. Recent evidence has demonstrated that supraphysiological shear stress from continuous-flow LVADs accelerates von Willebrand factor (vWF) metabolism by the action of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13) (the vWF protease).

Comparison of central venous catheterization techniques in pediatric patients: needle vs angiocath.

Background: A needle or an angiocath has been generally used as a route for inserting a guide wire during central venous catheterization. We compared the needle with the angiocath for ultrasound-guided central venous catheterization in pediatric patients concerning accuracy and easiness.

Methods: One hundred and thirty-two patients aged between 1 day and 5 years were randomized into the needle and the angiocath groups.

Comparison of the efficacy and safety of different doses of propacetamol for postoperative pain control after breast surgery.

Intravenous propacetamol has been shown to be effective for postoperative pain control. However, the recommendations regarding propacetamol doses for pain control are vague. The present study was performed to compare the efficacy and safety of propacetamol at a dose of 1 g or 2 g.