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.

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.

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.

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.

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.

Predictors of costs from the hospital perspective of primary pulmonary embolism.

The objective of this study was to estimate the total hospital cost per patient admitted through the emergency department with a primary diagnosis of pulmonary embolism (PE), and to identify the main components and predictors of costs.Actual costs of care of 652 consecutive patients hospitalised in 10 general hospitals in Belgium, including 31 outlier patients in terms of length of stay (4.8%), were obtained by aggregating all cost components contributing to care of each patient.In both inlier and outlier patients, the mean total cost per patient increased linearly with the degree of severity of illness classes related to the All Patient Refined Diagnosis Related Group (p<0.0001). Medical procedures, nursing activities and hospitalisation accommodation were the main cost components. We identified six independent predictors of costs in inliers: age group, chronic pulmonary heart disease, heart failure, admission to intensive care unit, initial thrombolysis treatment and type of hospital. There was a statistically significant linear trend between age groups and costs (p<0.0001).An increasing burden of comorbid illness was strongly associated with increasing actual cost for caring hospitalised patients for PE. Increasing age was associated with an increase in all main cost components.

Impact of hyponatremia on nerve conduction and muscle strength.

BACKGROUND: Hyponatremia is associated with unstable gait and propensity to falls. The potential contribution of peripheral nervous system dysfunction induced by hyponatremia has not yet been addressed by prospective studies. DESIGN: In the first part of this prospective study, we performed two tests evaluating muscle strength (grip test and quadriceps isometric contraction test) together with a timed up and go (TUG) test in 11 patients with chronic mild-to-moderate hyponatremia before and after the normalization of natremia. In the second part, we measured nerve conduction velocities and F-wave latencies in nine patients with profound hyponatremia (< 125 mmol/L) before and after the normalization of natremia. RESULTS: No significant change in muscle strength was observed when natremia was corrected from 127·7 ± 2·5 to 136·1 ± 1·8 mmol/L, contrary to a significant improvement in TUG from 14·9 ± 5·1 to 12·5 ± 4·7 s (P = 0·006). Nerve conduction velocities and F-wave latencies showed significant improvement in most of the studied nerves when natremia was corrected from 121·9 ± 2·4 to 135·5 ± 3·4 mmol/L (e.g. mean increase of 14·3% for motor nerve conduction and mean decrease of 21·6% for F-wave latency of left peroneal nerve). CONCLUSION: Whereas chronic mild-to-moderate hyponatremia has no impact on muscle strength, we demonstrate for the first time an impact of profound hyponatremia on nerve conduction studies. Further studies are needed to ascertain the contribution of these latter results on gait disturbances, propensity to falls and attention deficits associated with hyponatremia.

Blood storage duration and morbidity and mortality in children undergoing cardiac surgery. A retrospective analysis.

BACKGROUND: Blood transfusion is frequently required in children undergoing cardiac surgery and is associated with altered postoperative outcome. This may be due to alterations in red blood cell properties related to the storage process. OBJECTIVE: To evaluate the effect of blood storage duration on postoperative morbidity and mortality in children undergoing cardiac surgery. DESIGN: A retrospective review of a paediatric cardiac surgery database. SETTING: Department of Anaesthesiology, Queen Fabiola Children's University Hospital, Brussels, Belgium. PARTICIPANTS: Children transfused with one or two units of blood in the perioperative period. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Storage duration was used to allocate children to the Group 'Young' or the Group 'Old' (cut-off = 7 days). The primary endpoint was a composite based on the incidence of hospital mortality and/or the incidence of at least one organ failure. RESULTS: From 1014 children in the database, 570 were included in the final analysis. One hundred and eighteen patients were included in the Group 'Young' [median (interquartile range, IQR) storage duration 6 (5 to 7) days] and 452 in the Group 'Old' [storage duration 14 (11 to 19) days]. No difference was found in mortality, length of ICU stay, mechanical ventilation duration, postoperative infection and major organ dysfunction. Duration of storage used as a continuous variable did not influence the incidence of the composite endpoint when evaluated by univariate or multivariate logistic regression analyses. CONCLUSION: Red blood cell storage duration did not influence postoperative morbidity and mortality in paediatric cardiac surgery patients transfused with one or two units of blood.

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.).

Impact of entropy monitoring on volatile anesthetic uptake.

BACKGROUND: Electroencephalogram-derived monitoring to assess anesthetic depth may allow more accurate hypnotic drug administration, resulting in decreased anesthetic drug consumption. The authors hypothesized that the use of M-Entropy monitoring (Datex-Ohmeda, Helsinki, Finland) is associated with reduced sevoflurane uptake (primary outcome) in patients undergoing major abdominal surgery. METHODS: A total of 50 patients with an American Society of Anesthesiology score of II-III, scheduled for elective laparoscopic rectosigmoidectomy were randomized into two groups in this randomized controlled trial. In the control group, the target expiratory fraction of sevoflurane was adapted according to standard clinical practice. In the study group, the target expiratory fraction of sevoflurane was adapted to maintain state entropy values between 40 and 60. State entropy values were continuously recorded in both groups but were not available to the anesthesiologist in the control group. In both groups, patients were ventilated using the auto-control mode of the Zeus® (Dräger, Lübeck, Germany) respirator, which allows precise measurements of sevoflurane uptake. Sufentanil was administered using a target-controlled infusion system. RESULTS: Demographics did not differ between groups. During the anesthesia maintenance phase, state entropy values were lower in the control group than the study group (P < 0.0001). Sevoflurane uptake was higher in the control group than the study group (5.2 ± 1.4 ml/h vs. 3.8 ± 1.5 ml/h; P = 0.0012). Three patients in the control group developed intraoperative hypotension compared with none in the study group (P = 0.03). CONCLUSIONS: Monitoring the depth of anesthesia using M-Entropy was associated with a significant reduction in sevoflurane uptake.

Validation of use of the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form (ICIQ-UI-SF) for impairment rating: a transversal retrospective study of 120 patients.

AIMS: A urinary incontinence impairment rating must be a highly accurate, non-invasive exploration of the condition using International Classification of Functioning (ICF)-based assessment tools. The objective of this study was to identify the best evaluation test and to determine an impairment rating model of urinary incontinence. METHODS: In performing a cross-sectional study comparing successive urodynamic tests using both the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form (ICIQ-UI-SF) and the 1-hr pad-weighing test in 120 patients, we performed statistical likelihood ratio analysis and used logistic regression to calculate the probability of urodynamic incontinence using the most significant independent predictors. Subsequently, we created a template that was based on the significant predictors and the probability of urodynamic incontinence. RESULTS: The mean ICIQ-UI-SF score was 13.5 ± 4.6, and the median pad test value was 8 g. The discrimination statistic (receiver operating characteristic) described how well the urodynamic observations matched the ICIQ-UI-SF scores (under curve area (UDA):0.689) and the pad test data (UDA: 0.693). Using logistic regression analysis, we demonstrated that the best independent predictors of urodynamic incontinence were the patient's age and the ICIQ-UI-SF score. The logistic regression model permitted us to construct an equation to determine the probability of urodynamic incontinence. Using these tools, we created a template to generate a probability index of urodynamic urinary incontinence. CONCLUSIONS: Using this probability index, relative to the patient and to the maximum impairment of the whole person (MIWP) relative to urinary incontinence, we were able to calculate a patient's permanent impairment.

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.

Exercise testing to predict outcome in idiopathic versus associated pulmonary arterial hypertension.

We tested the ability of exercise testing to predict not only survival, but also time to clinical worsening (TTCW) in idiopathic versus associated pulmonary arterial hypertension (PAH). 136 patients with PAH (85 idiopathic and 51 with associated conditions) underwent cardiopulmonary exercise testing and a 6-min walk test. Death or transplantation, and clinical worsening events were recorded. 32 patients died and four had lung transplantation. In a univariate analysis, PAH patients survival was associated with oxygen uptake (V'(O(2))) at peak exercise and at the anaerobic threshold, ventilatory equivalent for carbon dioxide (minute ventilation (V'(E))/carbon dioxide production (V'(CO(2))) at the anaerobic threshold ((at))), V'(E)/V'(CO(2)) slope and distance walked. TTCW was associated with peak V'(O(2)) and V'(O(2),at), V'(E)/V'(CO(2),at), end-tidal carbon dioxide tension measured at the anaerobic threshold, peak oxygen pulse, increase in oxygen pulse and distance walked. In a multivariable analysis, distance walked and V'(E)/V'(CO(2),at) predicted survival, and only peak V'(O(2)) predicted TTCW. The receiver operating characteristic curve-derived cut-off values were 305 m for the 6-min walk distance, 54 for V'(E)/V'(CO(2),at) and 11.6 mL·kg(-1)·min for peak V'(O(2)). In the subgroup with associated PAH, no variable independently predicted either survival or clinical worsening. We conclude that several exercise variables predict survival and clinical stability in idiopathic PAH. Exercise variables are less accurate predictors of outcome in associated PAH.

Beta-blockers cause paracentesis-induced circulatory dysfunction in patients with cirrhosis and refractory ascites: a cross-over study.

BACKGROUND & AIMS: In patients with cirrhosis and refractory ascites the role of beta-blockers in the development of paracentesis-induced circulatory dysfunction (PICD) is unknown. The aim of this study was to investigate the incidence of PICD before and after discontinuation of beta-blockers in patients with cirrhosis and refractory ascites. A self control cross-over study was performed. METHODS: Patients with cirrhosis and refractory ascites treated with beta-blockers were selected. Heart rate, arterial pressure, and plasma renin concentrations (PRC) were collected before, immediately after and 1 week after large-volume paracentesis associated with intravenous albumin administration. Beta-blocker therapy was progressively discontinued after complete endoscopic eradication of varices. The clinical and biological evaluation was then repeated. The presence of PICD was defined as an increase in PRC of at least 50% above baseline 1 week after paracentesis. RESULTS: Ten patients were included (nine men, mean age 59.1 ± 10.7 years old). The MELD score was 17.7 ± 4.4 and eight patients were Child-Pugh C. When patients were given beta-blockers, the heart rate did not change immediately after paracentesis while mean arterial pressure significantly decreased; PICD developed in eight patients. After beta-blockers were discontinued, the heart rate significantly increased immediately after paracentesis and mean arterial pressure significantly decreased; PICD only developed in one patient; the difference in the incidence of PICD was significant when these same patients were treated with beta-blockers. CONCLUSIONS: The use of beta-blockers may be associated with a high risk of PICD in patients with cirrhosis and refractory ascites.