Objectives This study evaluated Multidimensional Geriatric Assessment (MGA) as predictor of mortality and major adverse cardiovascular and cerebral events (MACCE) after transcatheter aortic valve ...implantation (TAVI). Background Currently used global risk scores do not reliably estimate mortality and MACCE in these patients. Methods This prospective cohort comprised 100 consecutive patients ≥70 years undergoing TAVI. Global risk scores (Society of Thoracic Surgeons STS score, EuroSCORE) and MGA-based scores (cognition, nutrition, mobility, activities of daily living ADL, and frailty index) were evaluated as predictors of all-cause mortality and MACCE 30 days and 1 year after TAVI in regression models. Results In univariable analyses, all predictors were significantly associated with mortality and MACCE at 30 days and 1 year, except for the EuroSCORE at 30 days and instrumental ADL at 30 days and 1 year. Associations of cognitive impairment (odds ratio OR: 2.98, 95% confidence interval CI: 1.07 to 8.31), malnutrition (OR: 6.72, 95% CI: 2.04 to 22.17), mobility impairment (OR: 6.65, 95% CI: 2.15 to 20.52), limitations in basic ADL (OR: 3.63, 95% CI: 1.29 to 10.23), and frailty index (OR: 3.68, 95% CI: 1.21 to 11.19) with 1-year mortality were similar compared with STS score (OR: 5.47, 95% CI: 1.48 to 20.22) and EuroSCORE (OR: 4.02, 95% CI: 0.86 to 18.70). Similar results were found for 30-day mortality and MACCE. Bivariable analyses, including STS score or EuroSCORE suggested independent associations of MGA-based scores (e.g., OR of frailty index: 3.29, 95% CI: 1.06 to 10.15, for 1-year mortality in a model including EuroSCORE). Conclusions This study provides evidence that risk prediction can be improved by adding MGA-based information to global risk scores. Larger studies are needed for the development and validation of improved risk prediction models.
Summary Surgical site infections (SSIs) are among the most preventable health-care-associated infections and are a substantial burden to health-care systems and service payers worldwide in terms of ...patient morbidity, mortality, and additional costs. SSI prevention is complex and requires the integration of a range of measures before, during, and after surgery. No international guidelines are available and inconsistencies in the interpretation of evidence and recommendations of national guidelines have been identified. Given the burden of SSIs worldwide, the numerous gaps in evidence-based guidance, and the need for standardisation and a global approach, WHO decided to prioritise the development of evidence-based recommendations for the prevention of SSIs. The guidelines take into account the balance between benefits and harms, the evidence quality, cost and resource use implications, and patient values and preferences. On the basis of systematic literature reviews and expert consensus, we present 13 recommendations on preoperative preventive measures.
Summary Surgical site infections (SSIs) are the most common health-care-associated infections in developing countries, but they also represent a substantial epidemiological burden in high-income ...countries. The prevention of these infections is complex and requires the integration of a range of preventive measures before, during, and after surgery. No international guidelines are available and inconsistencies in the interpretation of evidence and recommendations in national guidelines have been identified. Considering the prevention of SSIs as a priority for patient safety, WHO has developed evidence-based and expert consensus-based recommendations on the basis of an extensive list of preventive measures. We present in this Review 16 recommendations specific to the intraoperative and postoperative periods. The WHO recommendations were developed with a global perspective and they take into account the balance between benefits and harms, the evidence quality level, cost and resource use implications, and patient values and preferences.
Objective We sought to evaluate whether in addition to cortisol, catecholamines also transfer psychosocial stress indirectly to the fetus by decreasing uterine blood flow (UBF) and increasing fetal ...anaerobic metabolism and stress hormones. Study Design Seven pregnant sheep chronically instrumented with uterine ultrasound flow probes and catheters at 0.77 gestation underwent 2 hours of psychosocial stress by isolation. We used adrenergic blockade with labetalol to examine whether decreased UBF is catecholamine mediated and to determine to what extent stress transfer from mother to fetus is catecholamine dependent. Results Stress induced transient increases in maternal cortisol and norepinephrine (NE). Maximum fetal plasma cortisol concentrations were 8.1 ± 2.1% of those in the mother suggesting its maternal origin. In parallel to the maternal NE increase, UBF decreased by maximum 22% for 30 minutes ( P < .05). Fetal NE remained elevated for >2 hours accompanied by a prolonged blood pressure increase ( P < .05). Fetuses developed a delayed and prolonged shift toward anaerobic metabolism in the presence of an unaltered oxygen supply. Adrenergic blockade prevented the stress-induced UBF decrease and, consequently, the fetal NE and blood pressure increase and the shift toward anaerobic metabolism. Conclusion We conclude that catecholamine-induced decrease of UBF is a mechanism of maternal-fetal stress transfer. It may explain the influence of maternal stress on fetal development and on programming of adverse health outcomes in later life especially during early pregnancy when fetal glucocorticoid receptor expression is limited.
Abstract Background We aimed to compare safety and efficacy of the direct thrombin inhibitor bivalirudin with unfractionated heparin (UFH) during transcatheter aortic valve implantation (TAVI). ...Methods In this retrospective analysis, 461 patients underwent TAVI between 2007 and 2012; 339 patients received bivalirudin, and 122 patients received UFH. In the bivalirudin group, the Sapien XT valve was implanted in 159 (46.9%) patients, and 180 (53.1%) received a Medtronic CoreValve. In the UFH group, only the Medtronic CoreValve was implanted. The primary outcome of interest was the incidence of any bleeding. Secondary outcomes of interest were all-cause mortality and cardiovascular mortality at 72 hours after the procedure and at 30 days. Results No significant difference between the groups was observed for life-threatening bleeding (2.4% for bivalirudin vs 3.3% for UFH; P = 0.59), major bleeding (8.3% vs 8.2%, respectively; P = 0.98) and minor bleeding (8.3% vs 7.4%, respectively; P = 0.76). At 72 hours after the procedure, all-cause mortality was 3.0% in the bivalirudin group and 3.3% for the UFH group ( P = 0.88), whereas cardiovascular mortality was 3.0% in the bivalirudin group and 2.5% in the heparin group ( P = 0.77). At 30 days, all-cause mortality was 5.3% vs 4.1% in the bivalirudin and heparin groups ( P = 0.57) and cardiovascular mortality was 4.4% vs 2.5% ( P = 0.33). Device success (Valve Academic Research Consortium 2 composite end point) was 94.0% in the bivalirudin-treated and 92.6% in the UFH-treated patients ( P = 0.60). The early safety at 30 days was 85.3% in the bivalirudin-treated group compared with 83.6% in the UFH-treated group ( P = 0.65). Conclusions Bivalirudin has a safety and efficacy profile similar to weight-adjusted UFH during the TAVI procedure.
Objective Glyoxalase 1 (GLO1) is ubiquitously expressed in the cytosol of the cell and is the major opponent against the reactive metabolite methylglyoxal, which is involved in the development of ...atherosclerosis. Nondiabetic individuals with an increased hemoglobin A1c (HbA1c ) level are at higher risk for development of cardiovascular diseases. As such, this study investigated whether there was an association between reduced GLO1 activity in atherosclerotic lesions of nondiabetic patients with an increased HbA1c level. Methods HbA1c level was determined in venous blood of patients with carotid artery disease. Protein level of GLO1 was measured in endarterectomy-derived carotid artery plaques by Western blotting. Activity was measured by spectrophotometric assay in the plaques as well as in the erythrocytes; GLO1 activity in erythrocytes was compared with that in a cohort of healthy individuals (n = 15; 33% men; average age, 60 years). Results There were 36 patients with carotid artery disease (69% men; average age, 69 years) included in this study and divided into two equal groups: group I, HbA1c < 5.7% (<39 mmol/mol); and group II, 5.7% ≤ HbA1c < 6.5% (39 mmol/mol ≤ HbA1c < 48 mmol/mol). GLO1 activity in carotid plaques was reduced by 29% in group II compared with group I ( P = .048), whereas protein expression was unchanged ( P = .25). Analysis of GLO1 activity in erythrocytes revealed no difference between the groups ( P = .36) or in comparison to healthy controls ( P = .15). Examination of clinical parameters showed an increased amount of patients with concomitant peripheral arterial disease in group II (44% vs 10%; P = .020). Conclusions Reduction of GLO1 activity in atherosclerotic lesions of nondiabetic patients with increased HbA1c is associated with a functional involvement of this protective enzyme in atherogenesis. Systemic GLO1 activity seems to be independent of both HbA1c and localized atherosclerosis as it was unchanged between group I and group II as well as compared with healthy controls, respectively.
Malignant mesothelioma (MM) of the pleura is an aggressive and often fatal neoplasm. Because MM frequently demonstrates marked angiogenesis, it may be responsive to antiangiogenic therapy, but ...effective methods for selecting and monitoring of patients are further needed. We employed dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and quantitative immunohistochemistry (IHC) to characterize the microvascularity of MM using both a physiologic and ultrastructural method.
Nineteen patients diagnosed with MM were enrolled and DCE-MRI was performed before antiangiogenic treatment. For each patient, tumor regions were characterized by their DCE-MRI-derived pharmacokinetic parameters (Amp, k(ep), k(el)), which were also compared to those of normal tissue (aorta, liver, spleen, and muscle). In addition, quantitative IHC of representative samples was performed with CD-34 staining to compare the calculated microvessel density (MVD) results with DCE-MRI results.
MM demonstrated markedly abnormal pharmacokinetic properties compared with normal tissues. Among the parameters tested, Amp was significantly different in MM (P < or = .001) compared to normal organs. Despite the observation that the MVD of mesotheliomas in this series was high compared to other tumors, DCE-MRI pharmacokinetic parameters had a moderately positive correlation with MVD (r = 0.5).
DCE-MRI and IHC can be used in patients with MM to visualize tumor microvascularity and to characterize tumor heterogeneity. DCE-MRI and IHC results positively correlated, though moderately, but these two methods present as essential tumor biomarkers. This multimodal characterization may be useful in selecting possible tumor subtypes that would benefit from antiangiogenic therapy.
Summary Background The role of the operating room's ventilation system in the prevention of surgical site infections (SSIs) is widely discussed, and existing guidelines do not reflect current ...evidence. In this context, laminar airflow ventilation was compared with conventional ventilation to assess their effectiveness in reducing the risk of SSIs. Methods We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and WHO regional medical databases from Jan 1, 1990, to Jan 31, 2014. We updated the search for MEDLINE for the period between Feb 1, 2014, and May 25, 2016. We included studies most relevant to our predefined question: is the use of laminar airflow in the operating room associated with the reduction of overall or deep SSI as outcomes in patients of any age undergoing surgical operations? We excluded studies not relevant to the study question, studies not in the selected languages, studies published before Jan 1, 1990, or after May 25, 2016, meeting or conference abstracts, and studies of which the full text was not available. Data were extracted by two independent investigators, with disagreements resolved through further discussion. Authors were contacted if the full-text article was not available, or if important data or information on the paper's content was absent. Studies were assessed for publication bias. Grading of recommendations assessment, development, and evaluation was used to assess the quality of the identified evidence. Meta-analyses were done with RevMan (version 5.3). Findings We identified 1947 records of which 12 observational studies were comparing laminar airflow ventilation with conventional turbulent ventilation in orthopaedic, abdominal, and vascular surgery. The meta-analysis of eight cohort studies showed no difference in risk for deep SSIs following total hip arthroplasty (330 146 procedures, odds ratio OR 1·29, 95% CI 0·98–1·71; p=0·07, I2 =83%). For total knee arthroplasty, the meta-analysis of six cohort studies showed no difference in risk for deep SSIs (134 368 procedures, OR 1·08, 95% CI 0·77–1·52; p=0·65, I2 =71%). For abdominal and open vascular surgery, the meta-analysis of three cohort studies found no difference in risk for overall SSIs (63 472 procedures, OR 0·75, 95% CI 0·43–1·33; p=0·33, I2 =95%). Interpretation The available evidence shows no benefit for laminar airflow compared with conventional turbulent ventilation of the operating room in reducing the risk of SSIs in total hip and knee arthroplasties, and abdominal surgery. Decision makers, medical and administrative, should not regard laminar airflow as a preventive measure to reduce the risk of SSIs. Consequently, this equipment should not be installed in new operating rooms. Funding None.
Summary Background We compared the efficacy and safety of the addition of lapatinib versus trastuzumab to anthracycline-taxane-based neoadjuvant chemotherapy. Methods In the GeparQuinto randomised ...phase 3 trial, patients with untreated HER2-positive operable or locally advanced breast cancer were enrolled between Nov 7, 2007, and July 9, 2010. Patients were eligible if their tumours were classified as cT3/4a-d, or hormone receptor (HR)-negative, HR-positive with clinically node-positive and cT2 disease (cT2 cN+), or HR-positive and pathologically node-positive in the sentinel lymph node for those with cT1 disease (cT1 pNSLN+ ). Patients were randomly assigned in a 1:1 ratio to receive neoadjuvant treatment with four cycles of EC (epirubicin 90 mg/m2 intravenously plus cyclophosphamide 600 mg/m2 intravenously, every 3 weeks), and four cycles of docetaxel (100 mg/m2 intravenously every 3 weeks) with either trastuzumab (6 mg/kg intravenously, with a starting loading dose of 8 mg/kg, for eight cycles, every 3 weeks) or lapatinib (1000–1250 mg per day orally) throughout all cycles before surgery. Randomisation was done by dynamic allocation with the minimisation method of Pocock and patients were stratified by participating site, HR status, and extent of disease (cT1–3 cN0–2 vs T4 or N3). The primary endpoint was pathological complete response (defined as ypT0 and ypN0) and was analysed in all patients who received at least one cycle of EC. Participants and investigators were not masked to treatment assignment. Pathologists in centres assessing surgery outcomes were masked to group assignment. This trial is registered with ClinicalTrials.gov , number NCT00567554. Findings Of 620 eligible patients, 309 were randomly assigned to chemotherapy with trastuzumab (ECH-TH group) and 311 to chemotherapy with lapatinib (ECL-TL group). Two patients in the ECH-TH group and three patients in the ECL-TL group did not start treatment because of withdrawal of consent or immediate surgery. 93 (30·3%) of 307 patients in the ECH-TH group and 70 (22·7%) of 308 patients in the ECL-TL group had a pathological complete response (odds ratio OR 0·68 95%CI 0·47–0·97; p=0·04). Chemotherapy with trastuzumab was associated with more oedema (119 39·1% vs 88 28·7%) and dyspnoea (90 29·6% vs 66 21·4%), and ECL-TL with more diarrhoea (231 75·0% vs 144 47·4%) and skin rash (169 54·9% vs 97 31·9%). 43 (14·0%) patients discontinued in the ECH-TH group and 102 (33·1%) in the ECL-TL group. 70 serious adverse events were reported in the ECH-TH group and 87 in the ECL-TL group. Interpretation This direct comparison of trastuzumab and lapatinib showed that pathological complete response rate with chemotherapy and lapatinib was significantly lower than that with chemotherapy and trastuzumab. Unless long-term outcome data show different results, lapatinib should not be used outside of clinical trials as single anti-HER2-treatment in combination with neoadjuvant chemotherapy. Funding GlaxoSmithKline, Roche, and Sanofi-Aventis.
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