A Patient-Level Meta-Analysis of Intensive Glucose Control in Critically Ill Adults.

BACKGROUND: Whether intensive glucose control reduces mortality in critically ill patients remains uncertain. Patient-level meta-analyses can provide more precise estimates of treatment effects than are currently available. METHODS: We pooled individual patient data from randomized trials investigating intensive glucose control in critically ill adults. The primary outcome was in-hospital mortality. Secondary outcomes included survival to 90 days and time to live cessation of treatment with vasopressors or inotropes, mechanical ventilation, and newly commenced renal replacement. Severe hypoglycemia was a safety outcome. RESULTS: Of 38 eligible trials (n=29,537 participants), 20 (n=14,171 participants) provided individual patient data including in-hospital mortality status for 7059 and 7049 participants allocated to intensive and conventional glucose control, respectively. Of these 1930 (27.3%) and 1891 (26.8%) individuals assigned to intensive and conventional control, respectively, died (risk ratio, 1.02; 95% confidence interval [CI], 0.96 to 1.07; P=0.52; moderate certainty). There was no apparent heterogeneity of treatment effect on in-hospital mortality in any examined subgroups. Intensive glucose control increased the risk of severe hypoglycemia (risk ratio, 3.38; 95% CI, 2.99 to 3.83; P<0.0001). CONCLUSIONS: Intensive glucose control was not associated with reduced mortality risk but increased the risk of severe hypoglycemia. We did not identify a subgroup of patients in whom intensive glucose control was beneficial. (Funded by the Australian National Health and Medical Research Council and others; PROSPERO number CRD42021278869.).

Analysis of admissions to intensive care units that could be supported on an intermediate care unit.

BACKGROUND: Only one third of European countries use intermediate care units (IMCs). An IMC makes it possible to manage patients who do not require intensive care but who need a higher level of nursing care that cannot be provided on the general ward. In Belgium, there are no national criteria for ICU admission or discharge, and no policies regarding IMC care or for differentiating ICU intensity levels. AIM/S: The aim of our study was to analyse the profile of ICU patients in Belgium on the basis of registered nursing activity in order to quantify the number of ICU days potentially transferable to an IMC. STUDY DESIGN: The study was conducted on 310 ICU beds. Patients admitted to the study were recruited during two different one-month periods in 2018 and were included into a prospective database that evaluated nursing workload carried out in 15 hospitals in the French-speaking part of Belgium. The number of ICU days that could be supported on an IMC was defined according to the Nursing Activities Score (NAS) items. RESULTS: A total of 3279 ICU patients for a total of 13 942 ICU days were included. 4987 days (35.8%) were considered as "transferable" to an IMC. The proportion of ICU days transferable to an IMC was highly variable among hospitals, ranging from 20.4% to 59.5% of all ICU days. On the day of ICU admission, 665/2142 (31.0%) of the patients were already identified as transferable to an IMC; this percentage significantly increased on day 2 (972/2066, 47.1%) and day 3 (650/1390, 46.7%). CONCLUSIONS: In Belgian ICUs, 35.8% of ICU hospital days, as per recorded NAS, do not necessitate intensive monitoring. These 35.8% of days of ICU hospitalization could be supported on an IMC. RELEVANCE FOR CLINICAL PRACTICE: In this study, a significant number of days spent in the ICU could be supported on an IMC, this could alleviate the workload of nurses and reduce the occupancy rate of intensive care units.

Intensive glucose control in critically ill adults: a protocol for a systematic review and individual patient data meta-analysis / Controle intensivo da glicose em adultos em estado grave: um protocolo de revisão sistemática e metanálise de dados individuais de pacientes

ABSTRACT Objective: The optimal target for blood glucose concentration in critically ill patients is unclear. We will perform a systematic review and meta-analysis with aggregated and individual patient data from randomized controlled trials, comparing intensive glucose control with liberal glucose control in critically ill adults. Data sources: MEDLINE®, Embase, the Cochrane Central Register of Clinical Trials, and clinical trials registries (World Health Organization, clinical trials.gov). The authors of eligible trials will be invited to provide individual patient data. Published trial-level data from eligible trials that are not at high risk of bias will be included in an aggregated data meta-analysis if individual patient data are not available. Methods: Inclusion criteria: randomized controlled trials that recruited adult patients, targeting a blood glucose of ≤ 120mg/dL (≤ 6.6mmol/L) compared to a higher blood glucose concentration target using intravenous insulin in both groups. Excluded studies: those with an upper limit blood glucose target in the intervention group of > 120mg/dL (> 6.6mmol/L), or where intensive glucose control was only performed in the intraoperative period, and those where loss to follow-up exceeded 10% by hospital discharge. Primary endpoint: In-hospital mortality during index hospital admission. Secondary endpoints: mortality and survival at other timepoints, duration of invasive mechanical ventilation, vasoactive agents, and renal replacement therapy. A random effect Bayesian meta-analysis and hierarchical Bayesian models for individual patient data will be used. Discussion: This systematic review with aggregate and individual patient data will address the clinical question, 'what is the best blood glucose target for critically ill patients overall?' Protocol version 0.4 - 06/26/2023 PROSPERO registration: CRD42021278869

RESUMO Objetivo: Não está claro qual é a meta ideal de concentração de glicose no sangue em pacientes em estado grave. Realizaremos uma revisão sistemática e uma metanálise com dados agregados e de pacientes individuais de estudos controlados e randomizados, comparando o controle intensivo da glicose com o controle liberal da glicose em adultos em estado grave. Fontes de dados: MEDLINE®, Embase, Cochrane Central Register of Clinical Trials e registros de ensaios clínicos (Organização Mundial da Saúde, clinical trials.gov). Os autores dos estudos qualificados serão convidados a fornecer dados individuais de pacientes. Os dados publicados em nível de ensaio qualificado que não apresentem alto risco de viés serão incluídos em uma metanálise de dados agregados se os dados individuais de pacientes não estiverem disponíveis. Métodos: Critérios de inclusão: ensaios clínicos controlados e randomizados que recrutaram pacientes adultos, com meta de glicemia ≤ 120mg/dL (≤ 6,6mmol/L) comparada a uma meta de concentração de glicemia mais alta com insulina intravenosa em ambos os grupos. Estudos excluídos: aqueles com meta de glicemia no limite superior no grupo de intervenção > 120mg/dL (> 6,6mmol/L), ou em que o controle intensivo de glicose foi realizado apenas no período intraoperatório, e aqueles em que a perda de seguimento excedeu 10% até a alta hospitalar. Desfecho primário: Mortalidade intra-hospitalar durante a admissão hospitalar. Desfechos secundários: Mortalidade e sobrevida em outros momentos, duração da ventilação mecânica invasiva, agentes vasoativos e terapia de substituição renal. Utilizaremos metanálise bayesiana de efeito randômico e modelos bayesianos hierárquicos para dados individuais de pacientes. Discussão: Essa revisão sistemática com dados agregados e de pacientes individuais abordará a questão clínica: Qual é a melhor meta de glicose no sangue de pacientes graves em geral? Protocolo versão 0.4 - 26/06/2023 Registro PROSPERO: CRD42021278869

Beneficial Effects of Tacrolimus on Brain-Death-Associated Right Ventricular Dysfunction in Pigs.

BACKGROUND: Right ventricular (RV) dysfunction remains a major problem after heart transplantation and may be associated with brain death (BD) in a donor. A calcineurin inhibitor tacrolimus was recently found to have beneficial effects on heart function. Here, we examined whether tacrolimus might prevent BD-induced RV dysfunction and the associated pathobiological changes. METHODS: After randomized tacrolimus (n = 8; 0.05 mg·kg-1·day-1) or placebo (n = 9) pretreatment, pigs were assigned to a BD procedure and hemodynamically investigated 1, 3, 5, and 7 h after the Cushing reflex. After euthanasia, myocardial tissue was sampled for pathobiological evaluation. Seven pigs were used as controls. RESULTS: Calcineurin inhibition prevented increases in pulmonary vascular resistance and RV-arterial decoupling induced by BD. BD was associated with an increased RV pro-apoptotic Bax-to-Bcl2 ratio and RV and LV apoptotic rates, which were prevented by tacrolimus. BD induced increased expression of the pro-inflammatory IL-6-to-IL-10 ratio, their related receptors, and vascular cell adhesion molecule-1 in both the RV and LV. These changes were prevented by tacrolimus. RV and LV neutrophil infiltration induced by BD was partly prevented by tacrolimus. BD was associated with decreased RV expression of the ß-1 adrenergic receptor and sarcomere (myosin heavy chain [MYH]7-to-MYH6 ratio) components, while ß-3 adrenergic receptor, nitric oxide-synthase 3, and glucose transporter 1 expression increased. These changes were prevented by tacrolimus. CONCLUSIONS: Brain death was associated with isolated RV dysfunction. Tacrolimus prevented RV dysfunction induced by BD through the inhibition of apoptosis and inflammation activation.

Altered Left Ventricular Rat Gene Expression Induced by the Myosin Activator Omecamtiv Mecarbil.

To explore the impact of omecamtiv mecarbil (OM) on the gene expression profile in adult male rats. Fourteen male Wistar rats were randomly assigned to a single OM (1.2 mg/kg/h; n = 6) or placebo (n = 8) 30-min infusion. Echocardiography was performed before and after OM infusion. Seven days after infusion, rats were euthanized, and left ventricular (LV) tissues were removed for real-time quantitative polymerase chain reaction (RTq-PCR) experiments. After OM infusion, pro-apoptotic Bax-to-Bcl2 ratio was decreased, with increased Bcl2 and similar Bax gene expression. The gene expression of molecules regulating oxidative stress, including glutathione disulfide reductase (Gsr) and superoxide dismutases (Sod1/Sod2), remained unchanged, whereas the expression of antioxidant glutathione peroxidase (Gpx) increased. While LV gene expression of key energy sensors, peroxisome proliferator activator (Ppar) α and γ, AMP-activated protein kinase (Ampk), and carnitine palmitoyltransferase 1 (Cpt1) remained unchanged after OM infusion, and the expression of pyruvate dehydrogenase kinase 4 (Pdk4) increased. The LV expression of the major myocardial glucose transporter Glut1 decreased, with no changes in Glut4 expression, whereas the LV expression of oxidized low-density lipoprotein receptor 1 (Olr1) and arachidonate 15-lipoxygenase (Alox15) increased, with no changes in fatty acid transporter Cd36. An increased LV expression of angiotensin II receptors AT1 and AT2 was observed, with no changes in angiotensin I-converting enzyme expression. The Kalikrein-bradykinin system was upregulated with increased LV expression of kallikrein-related peptidases Klk8, Klk1c2, and Klk1c12 and bradykinin receptors B1 and B2 (Bdkrb1 and Bdkrb2), whereas the LV expression of inducible nitric oxide synthase 2 (Nos2) increased. LV expression in major molecular determinants involved in calcium-dependent myocardial contraction remained unchanged, except for an increased LV expression of calcium/calmodulin-dependent protein kinase II delta (Cacna1c) in response to OM. A single intravenous infusion of OM, in adult healthy rats, resulted in significant changes in the LV expression of genes regulating apoptosis, oxidative stress, metabolism, and cardiac contractility.

Intensive glucose control in critically ill adults: a protocol for a systematic review and individual patient data meta-analysis.

OBJECTIVE: The optimal target for blood glucose concentration in critically ill patients is unclear. We will perform a systematic review and meta-analysis with aggregated and individual patient data from randomized controlled trials, comparing intensive glucose control with liberal glucose control in critically ill adults. DATA SOURCES: MEDLINE®, Embase, the Cochrane Central Register of Clinical Trials, and clinical trials registries (World Health Organization, clinical trials.gov). The authors of eligible trials will be invited to provide individual patient data. Published trial-level data from eligible trials that are not at high risk of bias will be included in an aggregated data meta-analysis if individual patient data are not available. METHODS: Inclusion criteria: randomized controlled trials that recruited adult patients, targeting a blood glucose of ≤ 120mg/dL (≤ 6.6mmol/L) compared to a higher blood glucose concentration target using intravenous insulin in both groups. Excluded studies: those with an upper limit blood glucose target in the intervention group of > 120mg/dL (> 6.6mmol/L), or where intensive glucose control was only performed in the intraoperative period, and those where loss to follow-up exceeded 10% by hospital discharge. PRIMARY ENDPOINT: In-hospital mortality during index hospital admission. Secondary endpoints: mortality and survival at other timepoints, duration of invasive mechanical ventilation, vasoactive agents, and renal replacement therapy. A random effect Bayesian meta-analysis and hierarchical Bayesian models for individual patient data will be used. DISCUSSION: This systematic review with aggregate and individual patient data will address the clinical question, 'what is the best blood glucose target for critically ill patients overall?'Protocol version 0.4 - 06/26/2023PROSPERO registration:CRD42021278869.

Tacrolimus Prevents Mechanical and Humoral Alterations in Brain Death-induced Lung Injury in Pigs.

Rationale: Donor brain death-induced lung injury may compromise graft function after transplantation. Establishing strategies to attenuate lung damage remains a challenge because the underlying mechanisms remain uncertain. Objectives: The effects of tacrolimus pretreatment were evaluated in an experimental model of brain death-induced lung injury. Methods: Brain death was induced by slow intracranial infusion of blood in anesthetized pigs after randomization to tacrolimus (orally administered at 0.25 mg ⋅ kg-1 twice daily the day before the experiment and intravenously at 0.05 mg ⋅ kg-1 1 h before the experiment; n = 8) or placebo (n = 9) pretreatment. Hemodynamic measurements were performed 1, 3, 5, and 7 hours after brain death. After euthanasia of the animals, lung tissue was sampled for pathobiological and histological analysis, including lung injury score (LIS). Measurements and Main Results: Tacrolimus pretreatment prevented increases in pulmonary arterial pressure, pulmonary vascular resistance, and pulmonary capillary pressure and decreases in systemic arterial pressure and thermodilution cardiac output associated with brain death. After brain death, the ratio of PaO2 to FiO2 decreased, which was prevented by tacrolimus. Tacrolimus pretreatment prevented increases in the ratio of IL-6 to IL-10, VCAM1 (vascular cell adhesion molecule 1), circulating concentrations of IL-1ß, and glycocalyx-derived molecules. Tacrolimus partially decreased apoptosis (Bax [Bcl2-associated X apoptosis regulator]-to-Bcl2 [B-cell lymphoma-2] ratio [P = 0.07] and number of apoptotic cells in the lungs [P < 0.05]) but failed to improve LIS. Conclusions: Immunomodulation through tacrolimus pretreatment prevented pulmonary capillary hypertension as well as the activation of inflammatory and apoptotic processes in the lungs after brain death; however, LIS did not improve.

Impact of treatment delays on outcome of acute testicular torsion: a 15-year retrospective study.

INTRODUCTION: Preservation of the testicle is directly associated with the duration of torsion. The aim in this retrospective study was to identify factors that influence pre-and in-hospital times and measure the extent to which these times affect testicle survival. PATIENTS AND METHODS: A retrospective review of 116 patients who underwent exploration for testicular torsion between 2000 and 2015. Patients were divided into orchiectomy and salvaged testicle groups. Times in patient management and clinical features were compared with Mann-Whitney, chi-squared, and Fisher exact tests. Multivariate logistical regression was used to identify independent factors associated with orchiectomy. RESULTS: The median prehospital time of 48 h (15.4-138 h) in the orchiectomy group was longer than the 2.4 h (1.6 h-5.2h) in the salvaged group. Patients examined by a general practitioner (GP) prior to presenting at hospital had a median prehospital time of 48 h, compared to 3 h for patients not examined before presentation at hospital. In-hospital times between admission and operation room, as well as times between ultrasonography and operation room, were also longer in the orchiectomy group. Previous GP consultation (OR = 27.26, 95% CI 2.32-320.59, p = .009), prehospital time (OR = 1.04, 95% CI 1.01-1.07, p = .003) and nausea (OR = 9.25, 95% IC 1.33-64.52, p = .025) were independent predictive factors associated with orchiectomy. CONCLUSION: Prehospital time was a determining factor in orchiectomy. For each extra hour of prehospital delay, the risk of orchiectomy increased by 4%. The rate of orchiectomy was higher among patients who first consulted a GP.

Effects of hyperoxia and cardiovascular risk factors on myocardial ischaemia-reperfusion injury: a randomized, sham-controlled parallel study.

NEW FINDINGS: What is the central question of this study? The beneficial effects of supplemental oxygen in patients with acute myocardial infarction are still uncertain: what are the effects of ischaemia-reperfusion injury during hyperoxia and normoxia in mature rats with and without cardiovascular risk factors? What is the main finding and its importance? Despite elevated baseline oxidative stress in rodents with cardiovascular risk factors, hyperoxic reperfusion limited myocardial necrosis and anti/pro-oxidant imbalance in spontaneously hypertensive and Zucker rats. In contrast, this effect was exacerbated in healthy Wistar rats. These results suggest that oxygen supplementation may not be harmful in patients with acute myocardial injury. ABSTRACT: Recent studies on O2 supplementation in acute coronary syndrome patients are equivocal. We tested the hypothesis that oxidative stress is increased in rodents with cardiovascular risk factors and enhances ischaemia-reperfusion injury in the presence of hyperoxia. A total of 43 Wistar rats (WR), 30 spontaneously hypertensive rats (SHR) and 33 obese Zucker rats (ZR) were randomized in a sham procedure (one-third) or underwent a left anterior descending ligation of the coronary artery for 60 min (two-thirds). This was followed by 3 h of reperfusion while animals were randomized either in a hyperoxic (HR) or a normoxic reperfusion (NR) group. Myocardial infarction size and oxidative stress biomarkers (myeloperoxidase (MPO), malondialdehyde and total free thiols) were assessed in blood samples. Baseline troponin T was higher in SHR and ZR than in WR (both P < 0.001). Baseline total MPO was elevated in ZR in comparison to SHR and WR (both P < 0.001). SHR had lower thiol concentration compared to WR and ZR (P < 0.000001). HR was associated with a lower troponin T rise in SHR and ZR than in NR (both P < 0.001), while the reverse occurred in WR (P < 0.001). In SHR, HR limited total MPO increase as compared to NR (P = 0.0056) and the opposite effect was observed with total MPO in WR (P = 0.013). NR was associated with a drastic reduction of total thiols as compared to HR both in SHR and in ZR (both P < 0.001). Despite a heightened baseline oxidative stress level, HR limited myocardial necrosis and anti/pro-oxidant imbalance in SHR and ZR whereas this effect was exacerbated in healthy WR.

Improving NSAIDs Prescription in Emergency Services Unit by a Point-of-Care-Based Renal Function Evaluation.

BACKGROUND: Patients evaluated in our emergency department (ED) often receive nonsteroidal anti-inflammatory drugs (NSAIDs) without any determination of their renal function, despite the known nephrotoxicity of NSAIDs. Guidelines recommend NSAID avoidance in patients with estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2, and long-lasting therapy is not recommended in people with chronic kidney disease. OBJECTIVE: We aimed to highlight the influence of a rapid measurement of the eGFR on NSAID prescriptions in patients at risk of impaired renal function using a point-of-care (POC) device. Our goal was to prevent the potential nephrotoxicity of NSAIDs by allowing the physicians to modify their treatments after eGFR determination, while avoiding a standard blood test for patients that would extend the duration of stay in the ED. METHODS: We included 192 patients evaluated in the ED for minor trauma or injury, with an indication of treatment with NSAIDs and no known contraindication to NSAIDs. Emergency physicians were asked to register their intention to actually prescribe NSAIDs based on their clinical gestalt with specific regard to kidney function. Immediately after, the creatinine level was measured in capillary blood and eGFR was calculated using the POC device (StatSensor Creatinine; Nova Biomedical, Waltham, MA). Our physicians avoided NSAID prescriptions when eGFR was < 30 mL/min/1.73 m2, and prescribed a shorter NSAID regimen therapy in patient with eGFR < 45 mL/min/1.73 m2, with a reminder to assure hydration. The decision based on eGFR was compared with original clinician intention. RESULTS: The clinicians intended to treat 164 patients with NSAIDs (group 1) and defer NSAIDs in 28 patients (group 2). In the first group, eGFR results supported no change in intended NSAID use in 144 patients, highlighted the need for a short regimen in 17 patients, and indicated contraindication to NSAIDs in 3 patients. In group 2, eGFR determination allowed prescription of NSAIDs in 21 patients, allowed utilization of NSAIDs with a short course in 5 patients, and supported the clinician decision to avoid NSAIDs in 2 patients. CONCLUSIONS: POC measurement of creatinine with eGFR estimation changed the prescription of NSAIDs in almost 25% of patients with previously unknown renal function.

Sepsis is frequent in initially non-critical hypotensive emergency department patients and is associated with increased mortality.

OBJECTIVE: Hypotension, defined as a mean arterial pressure of maximum 70 mmHg, is associated with significant morbidity and mortality. The objective of this study was to determine in initially non-critical hypotensive adult patients the proportion of sepsis and if septic patients had different outcome and clinical factors than non-septic patients. METHODS: This retrospective observational study was conducted over a year on adult hypotensive emergency department patients initially considered by triage as non-critical. Patients were separated into three groups: hypotensive septic patients (HSP), hypotensive non-septic infected patients (HNSIP), and other hypotensive patients (OHP). Clinical scores, signs, length of stay (LOS), and mortality were compared using analysis of variance for continuous variables and chi-square analysis for categorical variables. RESULTS: There were 136 (35.5%) septic patients, 37 (9.7%) with non-septic infection, and 210 (54.8%) with another cause of hypotension. Overall in-hospital mortality was 12.0% and total mortality was greater in HSP than in HNSIP (20.6% vs. 5.4%, p = 0.031) or OHP (20.6 vs. 7.6%, p < 0.001). LOS was greater for HSP when compared to HNSIP (median(IQR): 9(6-17) vs. 6(1-13), p = 0.004) and OHP (median(IQR): 9(6-17) vs. 3(1-8) days, p < 0.0001). CONCLUSION: Sepsis in a priori non-critical hypotensive adult patients, when compared with other causes of hypotension, is associated with significantly higher mortality and increased LOS. Patients that present to the emergency department and have a MAP of 70mmHg or less must be rigorously evaluated and have consistent follow-up.

Contegra versus pulmonary homograft for right ventricular outflow tract reconstruction in newborns.

OBJECTIVES: Pulmonary homografts are standard alternatives to right ventricular outflow tract reconstruction in congenital heart surgery. Unfortunately, shortage and conduit failure by early calcifications and shrinking are observed for small-sized homografts in younger patients. In neonates, Contegra® 12 mm (Medtronic Inc., Minneapolis, Minnesota, United States of America) could be a valuable alternative, but conflicting evidence exists. There is no published study considering only newborns with heterogeneous pathologies. We retrospectively compared the outcomes of these two conduits in this challenging population. METHODS: Patients who underwent a right ventricular outflow tract reconstruction between January 1992 and December 2014 at the Hôpital Universitaire des Enfants Reine Fabiola were included. We retrospectively collected and analysed demographic, echocardiographic, surgical, and follow-up data. RESULTS: Of the 53 newborns who benefited from a right ventricular outflow tract reconstruction during the considered period, 30 received a Contegra 12 mm (mean age 15 ± 8 days), and 23 a small (9-14 mm) pulmonary homograft (mean age 10 ± 7 days). Overall mortality was 16.6% with Contegra versus 17.4% in the pulmonary homograft group (p = 0.98 log-rank). Operative morbidity and early re-operation for conduit failure were not significantly different between the two groups. Mean follow-up in this study is 121 ± 74 months. Survival free from re-operation was not different between the two groups (p = 0.15). Multivariable analysis showed that weight and significant early gradient were factors associated with anticipated conduit failure. CONCLUSIONS: Contegra 12 mm is a valid alternative to small pulmonary homografts in a newborn patient population. TRIAL REGISTRATION: NCT03348397.

Bilateral Internal Mammary Artery Bypass Grafting: Sternal Wound Infection in High-Risk Population. Should Sternal Infection Scare Us?

BACKGROUND: Bilateral internal mammary arteries (BIMAs) remain underused in coronary artery bypass grafting (CABG), especially in elderly, diabetic, and obese patients. This study investigated incidence of sternal wound infection (SWI), sternal instability (SI), and reintervention for bleeding (RIB) in this high-risk population. METHODS: A single-center retrospective observational study was performed in "Grand Hôpital de Charleroi, Gilly, Belgium." A total of 319 patients undergoing CABG from December 2011 to December 2015 were included. Three main outcome measures (SWI, SI, and RIB) were investigated in obese vs nonobese, diabetic vs nondiabetic, and elderly vs younger patients. RESULTS: In all, 14 SWI, 11 SI, and 6 RIB were discounted. Death rate was as follows: SWI: 2/14 vs 17/305 (P = .178), SI: 2/11 vs 17/308 (P = .081), and RIB: 2/6 vs 17/313 (P = .004). In obese (n = 113) vs nonobese (n = 206) patients, there was no difference for SWI (P = .263), SI (P = .565), and RIB (P = .332). In diabetic (n = 118) vs nondiabetic (n = 201) patients, there was no difference for SWI (P = .642), SI (P = .497), and RIB (P = .298). In elderly (n = 62) vs younger (n = 257) patients, there was no difference for SWI (P = .619), SI (P = .915), and RIB (P = .385). CONCLUSIONS: Obesity, age, and diabetes treated by insulin (or not) do not seem to be risk factors for developing SWI, SI, or RIB in patients receiving a CABG using BIMA. Nevertheless, mortality was higher in RIB group.

Baseline hepcidin measurement in the differential diagnosis of anaemia for elderly patients and its correlation with the increment of transferrin saturation following an oral iron absorption test.

Background Anaemia is often multifactorial in the elderly, with a frequent association between iron deficiency anaemia (IDA) and anaemia of chronic disease (ACD). The primary objective of our study was to investigate whether baseline hepcidin measurement could be useful for identifying iron deficiency (ID) in anaemic elderly patients. The secondary objective was to assess whether baseline hepcidin concentrations correlated with the relative increase of transferrin saturation (TS) after an oral iron absorption test (OIAT). Methods Blood samples were collected between 7:30 am and 10:00 am in 328 geriatric outpatients, 102 underwent the OIAT. Types of anaemia were classified according biochemical and clinical criteria. TS and hepcidin were measured at baseline and 4 h after the iron dose. The ability of baseline hepcidin measurement to highlight ID in elderly anaemic patients was assessed using a receiver operator curve (ROC) analysis. Correlations between baseline hepcidin levels and the increment of TS following the OIAT were investigated using the Spearman coefficient. Results Among 328 included patients, 78 (23.8%) suffered from anaemia; 13 (4.0%), 19 (5.8%), 27 (8.2%) and 19 (5.8%) patients fulfilled criteria for IDA, IDA/ACD, ACD and unexplained anaemia, respectively. By multivariable analysis, creatinine, C-reactive protein, ferritin, Delta TS and Delta hepcidin were independently associated with baseline hepcidin concentrations. The area under the ROC curve (95% confidence interval) was 0.900 (0.830-0.970) for baseline hepcidin measurement. Baseline hepcidin levels correlated negatively with the relative increase in TS with a Spearman coefficient of -0.742. Conclusions Baseline hepcidin levels could be a useful tool to identify ID in anaemic elderly patients and may predict acute iron response following OIAT.

Differential Effects of E-Cigarette on Microvascular Endothelial Function, Arterial Stiffness and Oxidative Stress: A Randomized Crossover Trial.

Propylene glycol and glycerol are electronic cigarettes vehicles allowing liquid vaporization and nicotine transport. The respective effects of these different constituents on the cardiovascular system are unknown. We assessed the differential effects of vehicles (propylene glycol and glycerol) and nicotine on microcirculatory function, arterial stiffness, hemodynamic parameters and oxidative stress. Twenty-five tobacco smokers were exposed to vaping with and without nicotine, and sham vaping, in a randomized, single blind, 3-period crossover design study. Neither sham-vaping nor vaping in the absence of nicotine resulted in modifications of cardiovascular parameters or oxidative stress. In contrast, vaping with nicotine: 1) impaired acetylcholine mediated vasodilation (mean ± standard error mean) (area under curve, perfusion unit (PU), 3385 ± 27PU to 2271 ± 27PU, p < 0.0001); 2) increased indices of arterial stiffness, namely augmentation index corrected for heart rhythm (-3.5 ± 1.5% to 1.9 ± 2.3%; p = 0.013) and pulse wave velocity (4.9 ± 0.1 m.s-1 to 5.3 ± 0.1 m.s-1; p < 0.0001); 3) increased systolic and diastolic blood pressures as well as heart rate (all p < 0.0001) and finally; 4) raised plasma myeloperoxidase (median [interquartile range]) (13.6 ng.ml-1 [10-17.7] to 18.9 ng.ml-1 [12.2-54.4], p = 0.005). Our findings demonstrated that high temperature e-cigarette vehicle vaporization does not alter micro- and macro-vascular function, and oxidative stress, and that these effects are solely attributable to nicotine.

[Early postsurgical temozolomide treatment in newly diagnosed bad prognosis glioblastoma patients: Feasibility study]. / Administration précoce de témozolomide après chirurgie chez des patients ayant un glioblastome de mauvais pronostic : étude de faisabilité.

INTRODUCTION: Despite the combined adjuvant treatment of radiotherapy plus chemotherapy with temozolomide (TMZ) followed by 6 cycles of temozolomide after surgery, the prognosis of patients with glioblastoma remains poor. We conducted a monocentric prospective study to explore the tolerance and potential efficacy of an early temozolomide cycle after surgery. METHOD: Patients with newly diagnosed glioblastoma (unmutated IDH1) and of poor prognosis (age>50 years, biopsy or partial resection or unmethylated MGMT promoter) were prospectively included from June 2014 to 2017. They all received a cycle of 5 days of temozolomide between surgery and the combined adjuvant treatment. RESULTS: Twelve patients of median age 64.5 years (45-73) were included in the study. The median doses of temozolomide administered were respectively 265mg (225-300) for the early cycle; 130mg (110-150) for the concomitant treatment and 310mg (225-400) for the adjuvant one. Side effects during treatment were grade III lymphopenia, grade III neutropenia, fatigue and nausea/vomiting respectively in 4, 1, 7 and 5 patients. Progression-free survival and overall survival were respectively 90% and 91.7% at 6 months; 58.3 and 71.3% at 12 months; 31.1 and 71.3% at 18 months. CONCLUSION: Early postsurgical temozolomide treatment prior to standard adjuvant therapy for poor prognosis glioblastoma patients in our small prospective series presents toxicity and survival similar to those published in the literature for the general population of glioblastoma. These encouraging results should be confirmed by a multicentric study comparing this regiment with the standard treatment.

Focal Treatment for Unilateral Prostate Cancer Using High-Intensity Focal Ultrasound: A Comprehensive Study of Pooled Data.

BACKGROUND: Focal therapy for prostate cancer (PCa) remains experimental. Aim of the current study is to review available evidence and perform a pooled analysis exploring oncologic and functional results of high intensity focus ultrasound (HIFU) focal therapy for the treatment of unilateral PCa. METHODS: The National Library of Medicine Database was searched for relevant articles. A wide search was performed, including the combination of following words: "HIFU," "prostate," "cancer," and "focal." Overall, 167 articles were reviewed. Of these, seven articles were identified and eligible for the pooled analysis. Data on HIFU hemiablation or focal prostate ablation, oncologic and functional results were pooled from these seven studies that included 366 men with unilateral PCa. RESULTS: In the 366 analyzed cases, mean age was 67 years (95% confidence interval 66-69), and mean preoperative prostate-specific antigen was 6.4 ng/cc (5.5-7.4). Three studies included PCa up to Gleason 7 (3 + 4), three studies did include also Gleason 7 (4 + 3), whereas one study had no limitation in terms of Gleason score. Regarding early complications, low-grade Clavien-Dindo I-II were reported in 26% (16-37), whereas high-grade Clavien-Dindo ≥III were found in 3.8% (0-8.6). Analyzing oncologic outcomes mean follow-up was 26 months (23-31): at one year after HIFU, negative biopsy rate for clinically significant PCa was 87% (79-96), whereas salvage treatment-free survival rate was 92% (85-98). Regarding functional outcomes, reported potency rates were 74% (64-84), and continence 96% (91-100), although definitions of potency and continence were not homogenous across studies. CONCLUSIONS: This pooled analysis of the results of focal HIFU treatment of PCa shows promising oncologic and functional outcomes. Well-selected patients may be candidates for such a conservative partial treatment of the gland. Well-designed trials are awaited to compare HIFU focal treatment with current standard of care.

Arterial stiffness and cardiometabolic phenotype of Cameroonian Pygmies and Bantus.

BACKGROUND: Pygmies living in the Central African rainforest with a traditional hunter-gatherer lifestyle have a low incidence of cardiovascular diseases. Because of progressive loss of traditional habitat and ancestral lands, some Pygmies have migrated to urban areas and adopt specific Bantu lifestyles such as increased salt consumption and a sedentary way of life. We tested the hypothesis that migrant Pygmies could present with hemodynamic and metabolic characteristics different from those of traditional in-situ Pygmies and possibly closer to those of Bantu farmers. PATIENTS AND METHODS: The study included 148 Pygmies (94 traditional and 54 migrants) and 164 Bantus. Peripheral and central hemodynamics, aortic pulse wave velocity (PWV), and augmentation index corrected for heart rate (AIx) were measured, as well as fasting lipid profile. Urinary sodium and potassium excretion was also measured on a morning spot. RESULTS: Compared to Bantus, Pygmies had lower height (even between men and women, but men were taller than women in the three groups), weight, waist and hip circumference, peripheral and central blood pressure, total, low-density lipoprotein, and high-density lipoprotein cholesterol and apolipoprotein B100 levels, sodium urinary excretion, and lower prevalence of the metabolic syndrome. By contrast, they had a higher waist-to-hip ratio, and higher triglycerides levels, as compared to Bantu farmers. PWV and AIx did not differ between Bantus and Pygmies. Compared to traditional in-situ Pygmies, migrant Pygmies were not taller when adjusted for sex, had lower brachial and central blood pressure, higher PWV (adjusted for mean arterial pressure, BMI, and sex), and higher apolipoprotein B100 levels. In the whole population, multivariable analysis revealed that PWV was independently associated with age, weight, height, mean arterial pressure, total cholesterol, and hip circumference, whereas AIx was independently related to age, sex, height, heart rate, diastolic blood pressure, and group (from Bantu farmers to Pygmies). CONCLUSION: Comparisons between Bantus and Pygmies, and between migrant Pygmies and traditional in-situ Pygmies, showed mixed results, with favorable and deleterious hemodynamic and metabolic characteristics in all groups. This could be due to increased contacts between these populations, which blunt the expected differences and because the beneficial effects of the hunter-gatherer subsistence mode of traditional in-situ Pygmies are counterbalanced by unhealthy behavioral habits.

Management of supratentorial recurrent low-grade glioma: A multidisciplinary experience in 35 adult patients.

The management of recurrent diffuse low-grade gliomas (LGGs) is controversial. In the present study, the multidisciplinary management of 35 patients with recurrent LGGs was retrospectively analyzed. Tumor progression or recurrence was defined by clinical, radiological and/or metabolic pejorative evolution. All patients were regularly followed up by a multidisciplinary neuro-oncological group at Hôpital Erasme. Patients with histologically confirmed supratentorial LGGs (7 astrocytoma, 22 oligodendrogliomas and 6 oligoastrocytomas) who had undergone surgery between August 2004 and November 2010 were included. A total of 3 patients exhibited no tumor progression (median follow-up (FU), 81 months; range, 68-108 months). Tumor recurrence occurred in the 32 remaining patients [progression-free survival (PFS), 26 months; range, 2-104 months]. In addition, 25/29 (86%) patients who received surgery alone underwent reoperation at the time of tumor recurrence, and high-grade transformation occurred in 6 of these patients (24%). Furthermore, 4/29 (14%) patients were treated with adjuvant therapy alone (3 chemotherapy and 1 radiotherapy). In the 19 patients with no high-grade transformation at reintervention, 3 received adjuvant therapy and 16 were regularly followed up through multimodal imaging. The PFS time of the patients who underwent reoperation with close FU (n=16) and for the patients receiving adjuvant therapy with or without surgery (n=7) at first recurrence was 10 and 24 months (P=0.005), respectively. However, no significant difference was observed for overall survival (P=0.403). At the time of this study, 22 of the 35 patients included were alive following a median FU time of 109 months (range, 55-136). The results of the present study could change the multidisciplinary approach used into a more aggressive approach with adjuvant therapy, with or without surgery, for the treatment of a select subpopulation of patients with LGGs at the first instance of tumor recurrence.