Cardiac filling volumes versus pressures for predicting fluid responsiveness after cardiovascular surgery: the role of systolic cardiac function

ABSTRACT: INTRODUCTION: Static cardiac filling volumes have been suggested to better predict fluid responsiveness than filling pressures, but this may not apply to hearts with systolic dysfunction and dilatation. We evaluated the relative value of cardiac filling volume and pressures for predicting and monitoring fluid responsiveness, according to systolic cardiac function, estimated by global ejection fraction (GEF, normal 25 to 35%) from transpulmonary thermodilution. METHODS: We studied hypovolemic, mechanically ventilated patients after coronary (n = 18) or major vascular (n = 14) surgery in the intensive care unit. We evaluated 96 colloid fluid loading events (200 to 600 mL given in three consecutive 30-minute intervals, guided by increases in filling pressures), divided into groups of responding events (fluid responsiveness) and non-responding events, in patients with low GEF ( <20%) or near-normal GEF (≥20%). Patients were monitored by transpulmonary dilution and central venous (n = 9)/pulmonary artery (n = 23) catheters to obtain cardiac index (CI), global end-diastolic volume index (GEDVI), central venous (CVP) and pulmonary artery occlusion pressure (PAOP). RESULTS: Fluid responsiveness occurred in 8 (≥15% increase in CI) and 17 (≥10% increase in CI) of 36 fluid loading events when GEF was <20%, and 7 (≥15% increase in CI) and 17 (≥10% increase in CI) of 60 fluid loading events when GEF was ≥20%. Whereas a low baseline GEDVI predicted fluid responsiveness particularly when GEF was ≥20% (P = 0.002 or lower), a low PAOP was of predictive value particularly when GEF was <20% (P = 0.004 or lower). The baseline CVP was lower in responding events regardless of GEF. Changes in CVP and PAOP paralleled changes in CI particularly when GEF was <20%, whereas changes in GEDVI paralleled CI regardless of GEF. CONCLUSIONS: Regardless of GEF, CVP may be useful for predicting fluid responsiveness in patients after coronary and major vascular surgery provided that positive end-expiratory pressure is low. When GEF is low ( <20%), PAOP is more useful than GEDVI for predicting fluid responsiveness, but when GEF is near-normal (≥20%) GEDVI is more useful than PAOP. This favors predicting and monitoring fluid responsiveness by pulmonary artery catheter-derived filling pressures in surgical patients with systolic left ventricular dysfunction and by transpulmonary thermodilution-derived GEDVI when systolic left ventricular function is relatively norma

Lipid control and use of lipid-regulating drugs for prevention of cardiovascular events in Chinese type 2 diabetic patients: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Dyslipidaemia is an important but modifiable risk factor of cardiovascular disease (CVD) in type 2 diabetes. Yet, the effectiveness of lipid regulating drugs in Asians is lacking. We examined the effects of lipid control and treatment with lipid regulating drugs on new onset of CVD in Chinese type 2 diabetic patients.</p> <p>Methods</p> <p>In this prospective cohort consisting of 4521 type 2 diabetic patients without history of CVD and naïve for lipid regulating treatment recruited consecutively from 1996 to 2005, 371 developed CVD after a median follow-up of 4.9 years. We used Cox proportional hazard regression to obtain the hazard ratios (HR) of lipids and use of lipid regulating drugs for risk of CVD.</p> <p>Results</p> <p>The multivariate-adjusted HR (95% confidence interval) of CVD in patients with high LDL-cholesterol (≥ 3.0 mmol/L) was 1.36 (1.08 - 1.71), compared with lower values. Using the whole range value of HDL-cholesterol, the risk of CVD was reduced by 41% with every 1 mmol/L increase in HDL-cholesterol. Plasma triglyceride did not predict CVD. Statins use was associated with lower CVD risk [HR = 0.66 (0.50 - 0.88)]. In sub-cohort analysis, statins use was associated with a HR of 0.60 (0.44 - 0.82) in patients with high LDL-cholesterol (≥ 3.0 mmol/L) and 0.49 (0.28 - 0.88) in patients with low HDL-cholesterol. In patients with LDL-cholesterol < 3.0 mmol/L, use of fibrate was associated with HR of 0.34 (0.12 - 1.00). Only statins were effective in reducing incident CVD in patients with metabolic syndrome [(HR = 0.58(0.42--0.80)].</p> <p>Conclusions</p> <p>In Chinese type 2 diabetic patients, high LDL-cholesterol and low HDL-cholesterol predicted incident CVD. Overall, patients treated with statins had 40-50% risk reduction in CVD compared to non-users.</p

Complement-Mediated Virus Infectivity Neutralisation by HLA Antibodies Is Associated with Sterilising Immunity to SIV Challenge in the Macaque Model for HIV/AIDS.

Sterilising immunity is a desired outcome for vaccination against human immunodeficiency virus (HIV) and has been observed in the macaque model using inactivated simian immunodeficiency virus (SIV). This protection was attributed to antibodies specific for cell proteins including human leucocyte antigens (HLA) class I and II incorporated into virions during vaccine and challenge virus preparation. We show here, using HLA bead arrays, that vaccinated macaques protected from virus challenge had higher serum antibody reactivity compared with non-protected animals. Moreover, reactivity was shown to be directed against HLA framework determinants. Previous studies failed to correlate serum antibody mediated virus neutralisation with protection and were confounded by cytotoxic effects. Using a virus entry assay based on TZM-bl cells we now report that, in the presence of complement, serum antibody titres that neutralise virus infectivity were higher in protected animals. We propose that complement-augmented virus neutralisation is a key factor in inducing sterilising immunity and may be difficult to achieve with HIV/SIV Env-based vaccines. Understanding how to overcome the apparent block of inactivated SIV vaccines to elicit anti-envelope protein antibodies that effectively engage the complement system could enable novel anti-HIV antibody vaccines that induce potent, virolytic serological response to be developed

O-RADS US risk stratification and management system: A consensus guideline from the ACR ovarian-adnexal reporting and data system committee.

The Ovarian-Adnexal Reporting and Data System (O-RADS) US risk stratification and management system is designed to provide consistent interpretations, to decrease or eliminate ambiguity in US reports resulting in a higher probability of accuracy in assigning risk of malignancy to ovarian and other adnexal masses, and to provide a management recommendation for each risk category. It was developed by an international multidisciplinary committee sponsored by the American College of Radiology and applies the standardized reporting tool for US based on the 2018 published lexicon of the O-RADS US working group. For risk stratification, the O-RADS US system recommends six categories (O-RADS 0-5), incorporating the range of normal to high risk of malignancy. This unique system represents a collaboration between the pattern-based approach commonly used in North America and the widely used, European-based, algorithmic-style International Ovarian Tumor Analysis (IOTA) Assessment of Different Neoplasias in the Adnexa model system, a risk prediction model that has undergone successful prospective and external validation. The pattern approach relies on a subgroup of the most predictive descriptors in the lexicon based on a retrospective review of evidence prospectively obtained in the IOTA phase 1-3 prospective studies and other supporting studies that assist in differentiating management schemes in a variety of almost certainly benign lesions. With O-RADS US working group consensus, guidelines for management in the different risk categories are proposed. Both systems have been stratified to reach the same risk categories and management strategies regardless of which is initially used. At this time, O-RADS US is the only lexicon and classification system that encompasses all risk categories with their associated management schemes

SdrF, a Staphylococcus epidermidis Surface Protein, Contributes to the Initiation of Ventricular Assist Device Driveline–Related Infections

Staphylococcus epidermidis remains the predominant pathogen in prosthetic-device infections. Ventricular assist devices, a recently developed form of therapy for end-stage congestive heart failure, have had considerable success. However, infections, most often caused by Staphylococcus epidermidis, have limited their long-term use. The transcutaneous driveline entry site acts as a potential portal of entry for bacteria, allowing development of either localized or systemic infections. A novel in vitro binding assay using explanted drivelines obtained from patients undergoing transplantation and a heterologous lactococcal system of surface protein expression were used to identify S. epidermidis surface components involved in the pathogenesis of driveline infections. Of the four components tested, SdrF, SdrG, PIA, and GehD, SdrF was identified as the primary ligand. SdrF adherence was mediated via its B domain attaching to host collagen deposited on the surface of the driveline. Antibodies directed against SdrF reduced adherence of S. epidermidis to the drivelines. SdrF was also found to adhere with high affinity to Dacron, the hydrophobic polymeric outer surface of drivelines. Solid phase binding assays showed that SdrF was also able to adhere to other hydrophobic artificial materials such as polystyrene. A murine model of infection was developed and used to test the role of SdrF during in vivo driveline infection. SdrF alone was able to mediate bacterial adherence to implanted drivelines. Anti-SdrF antibodies reduced S. epidermidis colonization of implanted drivelines. SdrF appears to play a key role in the initiation of ventricular assist device driveline infections caused by S. epidermidis. This pluripotential adherence capacity provides a potential pathway to infection with SdrF-positive commensal staphylococci first adhering to the external Dacron-coated driveline at the transcutaneous entry site, then spreading along the collagen-coated internal portion of the driveline to establish a localized infection. This capacity may also have relevance for other prosthetic device–related infections

Characterisation of breast fine-needle aspiration biopsies by centrosome aberrations and genomic instability

Recent studies have suggested that aneuploidy in malignant tumours could be a consequence of centrosome aberrations. Using immunofluorescence analysis with an antibody against γ-tubulin and DNA image cytometry, we measured centrosome aberrations and DNA ploidy patterns in fine-needle aspiration biopsies (FNABs) of 58 breast lesions. Benign lesions did not show any centrosome aberrations. DNA diploid carcinomas showed a mean percentage of cells with centrosomal defects of 2.1%. The aneuploid invasive carcinomas could be divided into two subgroups by their significantly (P=0.0003) different percentage of cells with centrosome aberrations (2.0 and 10.3%, respectively) and their significantly (P=0.0003) different percentage of cells with nonmodal DNA content values determined by the Stemline Scatter Index (SSI), a measure of genomic instability. The percentage of cells with centrosome aberrations demonstrated a positive, linear correlation with the corresponding SSI (r=0.82, P<0.0001) and loss of tissue differentiation (r=0.78, P<0.0001). Our results indicate the percentage of cells with centrosome aberrations as being sufficient to divide the investigated tumours into three significantly different groups: benign lesions with no centrosomal aberrations, and two malignant tumour types with mean values of 2.1 and 9.6% of centrosomal defects, respectively. Together, these results demonstrate that centrosome aberrations correlate with genomic instability and loss of tissue differentiation. Furthermore, this study shows the feasibility of centrosomal analysis in FNAB of the breast and suggests centrosomal aberrations as possessing diagnostic and prognostic value

Chapter 4: Effective Search Strategies for Systematic Reviews of Medical Tests

This article discusses techniques that are appropriate when developing search strategies for systematic reviews of medical tests. This includes general advice for searching for systematic reviews and issues specific to systematic reviews of medical tests. Diagnostic search filters are currently not sufficiently developed for use when searching for systematic reviews. Instead, authors should construct a highly sensitive search strategy that uses both controlled vocabulary and text words. A comprehensive search should include multiple databases and sources of grey literature. A list of subject-specific databases is included in this article

Monitoring symptoms at home: What methods would cancer patients be comfortable using?

PURPOSE: This study aimed to determine which methods of remote symptom assessment cancer outpatients would be comfortable using, including those involving information technology, and whether this varied with age and gender. METHODS: A questionnaire survey of 477 outpatients attending the Edinburgh Cancer Centre in Edinburgh, UK. RESULTS: Most patients reported that they would not feel comfortable using methods involving technology such as a secure website, email, mobile phone text message, or a computer voice on the telephone but that they would be more comfortable using more traditional methods such as a paper questionnaire, speaking to a nurse on the telephone, or giving information in person. CONCLUSIONS: The uptake of new, potentially cost-effective technology-based methods of monitoring patients' symptoms at home might be limited by patients' initial discomfort with the idea of using them. It will be important to develop methods of addressing this potential barrier (such as detailed explanation and supervised practice) if these methods are to be successfully implemented

Population Pharmacokinetic Modelling of FE 999049, a Recombinant Human Follicle-Stimulating Hormone, in Healthy Women After Single Ascending Doses

OBJECTIVE: The purpose of this analysis was to develop a population pharmacokinetic model for a novel recombinant human follicle-stimulating hormone (FSH) (FE 999049) expressed from a human cell line of foetal retinal origin (PER.C6(®)) developed for controlled ovarian stimulation prior to assisted reproductive technologies.METHODS: Serum FSH levels were measured following a single subcutaneous FE 999049 injection of 37.5, 75, 150, 225 or 450 IU in 27 pituitary-suppressed healthy female subjects participating in this first-in-human single ascending dose trial. Data was analysed by nonlinear mixed effects population pharmacokinetic modelling in NONMEM 7.2.0.RESULTS: A one-compartment model with first-order absorption and elimination rates was found to best describe the data. A transit model was introduced to describe a delay in the absorption process. The apparent clearance (CL/F) and apparent volume of distribution (V/F) estimates were found to increase with body weight. Body weight was included as an allometrically scaled covariate with a power exponent of 0.75 for CL/F and 1 for V/F.CONCLUSIONS: The single-dose pharmacokinetics of FE 999049 were adequately described by a population pharmacokinetic model. The average drug concentration at steady state is expected to be reduced with increasing body weight