Effects of short vs. prolonged mechanical ventilation on antioxidant systems in piglet diaphragm

Objective Prolonged controlled mechanical ventilation (MV) is known to induce diaphragmatic oxidative stress that seems to be an important factor reducing force-generating capacity. To better understand the cellular mechanisms involved, this work examined the effect of short vs. prolonged MV on antioxidant defense in the diaphragm.Design and setting Prospective, randomized, controlled animal study in a university laboratory.Methods Eleven piglets (15–20 kg) were assigned to one of two groups: a long-MV group (n=6) ventilated for 3 days or a short-MV group (n=5) ventilated for 3 h. Force frequency curves of the transdiaphragmatic pressure (Pdi) were obtained in vivo by phrenic nerve pacing. Oxidative stress was evaluated by thiobarbituric reactive substance (TBARs) content and the enzymatic antioxidant activity of both superoxide dismutase (SOD) and glutathione peroxidase (GPx) in samples of diaphragm.Results Pdi decreased in the long-MV group by 30–35% over the 3 days at all frequencies compared to the short-MV group. Diaphragm TBARs content was significantly higher and SOD activity lower in long-MV animals than in short-MV animals after 72 h. GPx activity tended to be lower in diaphragms from long-MV animals, but this difference was not significant.Conclusions This study shows that 3 days of MV in piglets is associated with a decrease in antioxidant activity which could emphasize oxidative stress and both contribute to the diaphragm dysfunction caused by MVElectronic Supplementary Material Electronic supplementary material to this paper can be obtained by using the Springer Link server located at .S. Jaber and M. Sebbane contributed equally to this study.This article refers to the editorial     

Hippocampal functional magnetic resonance imaging during a face-name learning task in adolescents with antecedents of prematurity

Functional magnetic resonance imaging (fMRI) was used to map hippocampal activation during a declarative memory task in a sample of 14 adolescents with antecedents of prematurity (AP). The sample with AP was matched by age, sex and handedness with 14 full-term controls with no history of neurological or psychiatric illness. The target task consisted in learning 16 novel face-name pairs, and the control task involved the examination of two repeated face-name pairs. Stereological methods were also used to quantify hippocampal volumes. In both groups, we observed increased activation in the learning condition compared to the control task in the right fusiform gyrus and the left inferior occipital gyrus, but only premature subjects activated the hippocampus. Group comparison of the activation versus control conditions showed that prematures had greater activity in the right hippocampus than controls during the encoding of the word-face association. Volumetric analyses showed a significant left hippocampal volume loss in adolescents with AP. In addition, we found a significant positive correlation in the premature group between right hippocampal activation and face-name recognition. Functional MRI data also correlated with structural MRI data: right hippocampal activation correlated positively with right hippocampal volume. Our findings are consistent with previous studies of brain plasticity after focal lesions. Left hippocampal tissue loss may be related to an increase in contralateral brain activity, probably reflecting a compensatory mechanism. Our data also suggest that this plasticity is not enough to achieve normal performance.     

Regulation of peritoneal and systemic neutrophil-derived tumor necrosis factor-alpha release in patients with severe peritonitis: role of tumor necrosis factor-alpha converting enzyme cleavage

OBJECTIVE: Polymorphonuclear neutrophil (PMN) influx and peritoneal tumor necrosis factor (TNF)-alpha production are key host defense mechanisms during peritonitis. The aim of this study was to explore the potential interactions between TNF-alpha production and TNF-alpha converting enzyme (TACE) expression by PMN in the blood and peritoneum of patients with severe peritonitis. DESIGN: A prospective study. SETTING: A surgical adult intensive care unit in a university hospital. PATIENTS: A total of 29 consecutive immunocompetent patients with severe sepsis within 48 hrs of onset were enrolled and underwent laparotomy for a diffuse secondary peritonitis. Thirteen volunteers served as controls. MEASUREMENTS: Blood and peritoneal fluid recovered during laparotomy were analyzed and compared for 1) soluble TNF-alpha, soluble L-selectin, and type I and II TNF-alpha receptor levels; 2) PMN membrane TNF-alpha, membrane L-selectin, and TACE expression (flow cytometry); and 3) TNF-alpha production by cultured PMN. Correlations between these forms of PMN-derived TNF-alpha and the severity of the peritonitis and patient's outcome were investigated. MAIN RESULTS: Elevated soluble TNF-alpha levels in both plasma and peritoneal fluid from the patients were found, together with decreased expression of membrane TNF-alpha and TACE up-regulation at the PMN surface. Soluble L-selectin and type I and II TNF receptors were highly released, suggesting also the role of TACE. In contrast, the capacity of both blood and peritoneal PMN to synthesize TNF-alpha in vitro, in optimal conditions of stimulation (lipopolysaccharide + interferon-gamma), was impaired as compared with controls' blood PMN. Regulation of PMN-derived TNF-alpha was similar in the two compartments, but responses were more pronounced in the peritoneum. TACE up-regulation at the surface of blood-derived PMN correlated with the Sequential Organ Failure Assessment score and vital outcome. CONCLUSION: These human data demonstrate that mTACE is up-regulated at the PMN surface during severe peritonitis. This finding could be related to a paracrine regulatory loop involving some TACE substrates such as TNF-alpha, L-selectin, and TNF receptors.     

Curriculum directions and strategies for the implementation of a new pedagogic proposal

This study is aimed at contributing to the transformation movement to be developed in the Nursing Courses/Schools. The contribution refers to the formation of nurses with autonomy and discernment, to ensure the construction of the model of health attention, to the production of new knowledge and to the delivery of quality services directed to the health needs of the population. This study brings some conceptual and methodological reflections that may direct the change in the nurse formation process, as well as pointing strategies to implement the new pedagogic proposal from the challenge posed by the implementation of the National Curriculum Directions for Undergraduate Nursing Courses.     

HMR1402, a potassium ATP channel blocker during hyperdynamic porcine endotoxemia: effects on hepato-splanchnic oxygen exchange and metabolism

Objective To assess the effects of the potassium ATP (KATP) channel blocker HMR1402 (HMR) on systemic and hepato-splanchnic hemodynamics, oxygen exchange and metabolism during hyperdynamic porcine endotoxemia.Design Prospective, randomized, controlled study with repeated measures.Setting Animal laboratory.Subjects Eighteen pigs allocated to receive endotoxin alone (control group, CON, n=10) or endotoxin and HMR (6 mg/kg h^–1, n=8).Interventions Anesthetized, mechanically ventilated, and instrumented pigs receiving continuous i.v. endotoxin were resuscitated with hetastarch to maintain mean arterial pressure (MAP) >60 mmHg. Twelve hours after starting the endotoxin infusion, they received HMR or its vehicle for another 12 h.Results HMR transiently increased MAP by about 15 mmHg, but this effect was only present during the first 1 h of infusion. The HMR decreased cardiac output due to a fall in heart rate, and thereby reduced liver blood flow. While liver O₂ delivery and uptake remained unchanged, HMR induced hyperlactatemia [from 1.5 (1.1; 2.0), 1.4 (1.2; 1.8), and 1.2 (0.8; 2.0) to 3.1 (1.4; 3.2), 3.2 (1.6; 6.5), and 3.0 (1.0; 5.5) mmol/l in the arterial, portal and hepatic venous samples, respectively] and further increased arterial [from 8 (3; 13) to 23 (11; 57); p<0.05], portal [from 9 (4; 14) to 23 (14; 39); p<0.05] and hepatic vein [from 7 (0; 15) to 30 (8; 174), p<0.05] lactate/pyruvate ratios indicating impaired cytosolic redox state.Conclusion The short-term beneficial hemodynamic effects of KATP channel blockers have to be weighted with the detrimental effect on mitochondrial respiration.P. Asfar and Z. Iványi equally contributed to this work     

Percutaneous Osteotomies in Hallux Valgus: A Systematic Review

Percutaneous and minimally invasive surgery is one of the greatest advances in the operating field of orthopedic since the late 1990s. The potential advantages include a shorter operative time, quicker recovery, and reduced hospital stay compared with traditional open surgery. However, scientific validation of the safety and efficacy of hallux valgus (HV) percutaneous surgery remains inconclusive. The objective of the present study was to systematically review the published data and clinical evidence for percutaneous HV surgery, evaluate the scientific method of the reports, and clarify the indications, safety, efficacy, and potential risks of these surgical techniques. Two reviewers independently identified the studies using a PubMed search, with the keywords “hallux valgus,” “osteotomy,” “minimally invasive,” and “percutaneous.” Quality assessment was performed using the Coleman methodology scale, and each study was assigned a level of evidence and grade of recommendation. Eighteen studies were included and reported a total of 1534 procedures for percutaneous HV surgery on 1397 patients. Of the 18 studies, 14 (77.8%) were level IV, 2 (11.1%) were level III, and 2 (11.1%) were level II. Overall, the average angle correction of the HV deformity improved postoperatively. Regarding the complications, although some investigators revealed no major complications, others described deformity recurrence in 7.8%, stiffness of the first metatarsophalangeal joint in 9.8%, malunion in 4% to 8.7%, and infection rates ranging from 1.9% to 14.3%. The main indication for percutaneous HV surgery is the correction of mild deformities. The complication rate was elevated even in experienced surgeons. In conclusion, future research in percutaneous techniques should include adequately sized randomized control trials, standardization of treatment protocols, and the use of validated tools for the measurement of clinical outcomes.     

Comorbidity Burden in Trial-Aligned Patients with Established Gout in Germany,UK, US,and France: a Retrospective Analysis

Introduction

Patients with gout have numerous comorbidities. We aimed to estimate the prevalence and incidence rates of renal and cardiovascular morbidities in trial-aligned patients with established gout in Germany (DE), the United Kingdom (UK), the United States (US), and France (FR).

Methods

This longitudinal cohort study used retrospective data from IMS Disease Analyzer? (DE, FR), Clinical Practice Research Datalink–Hospital Episode Statistics (UK), and IMS’ PharMetrics Plus database linked with outpatient laboratory results (US). Included patients were ≥18 years at index date (January 1, 2010; all dates +1 year for FR), with continuous enrollment during the pre-index year, had “prevalent established gout” determined by data in the pre-index year, and ≥1 documented visit after index date; additional inclusion/exclusion criteria were aligned with recent gout clinical trials. Look-back for comorbidity prevalence extended to January 1, 2003 (US: January 1, 2009). Follow-up for incidence extended from index date to at most March 26, 2013 (FR: May 31, 2014). Events of interest were identified by diagnostic codes and/or laboratory data.

Results

The trial-aligned cohorts included 35,118 (DE), 24,607 (UK), 121,591 (US), and 17,338 (FR) patients. Among renal conditions, baseline diagnosis of chronic kidney disease/renal failure was most prevalent in the UK followed by DE; abnormal serum creatinine was most prevalent in the UK. Hypertension was the most prevalent cardiovascular diagnosis in all countries, followed by ischemic heart disease (IHD) and myocardial infarction. Incidence rates (per 100 patient-years) for new/worsening renal impairment ranged from 1.67 (DE) to 4.34 (US) and for nephrolithiasis diagnosis from 0.31 (FR) to 3.79 (US). The incidence rates for hypertension diagnosis were highest among cardiovascular-related events, ranging from 3.23 (UK) to 20.27 (US), followed by IHD.

Conclusions

Patients with established gout such as those included in gout trials have a high burden of established morbidity and new diagnoses of morbid events. Consideration of comorbidities, which greatly exacerbate disease burden, is important in gout management.

Funding

AstraZeneca.

     

Psychometric properties of the MOS (Medical Outcomes Study) Sleep Scale in patients with neuropathic pain.

OBJECTIVE: This study assessed the psychometric properties of the MOS Sleep Scale in neuropathic pain (NeP). METHODS: Psychometric properties were tested in patients with neuropathic pain enrolled in a prospective study exploring the effectiveness of gabapentin for 3 months. Participants also completed scales for pain intensity, anxiety, depression, disability, and health-related quality of life. Feasibility, reliability, validity and sensitivity to change were measured in this study. RESULTS: Six-hundred-three patients [58.4+/-14.4 years (65.1% female), mean+/-SD] with pain for 1.2+/-3.3 years were included. The MOS Sleep Scale was acceptable (items with missing data <10% and floor and ceiling effects <50% per item and <15% per domain) and reliable (Cronbach's alpha between 0.64 and 0.87, and test-retest intraclass correlation coefficients between 0.79 and 0.91, p<0.001 for all cases). After adjusting for confounders, the MOS Sleep Scale was able to distinguish between sex, present pain intensity, level of disability and presence of anxiety or depression. Correlations with other scales were moderate; rho-coefficients between -0.21 and 0.57 (p<0.01, all cases). The scale was sensitive to change after treatment with gabapentin; after adjusting, responders (50% reduction in baseline pain) showed a decrease in sleep problems index of -25.6+/-14.3 points vs. -12.1+14.5 points in nonresponders (F=80.5, df=1/398, p<0.0001). Score reduction in summary index and subscales correlated significantly with pain intensity reduction (Pearson r-coefficients between 0.428 and 0.116, p<0.01, all cases). CONCLUSIONS: The MOS Sleep Scale showed good psychometric properties and was sensitive to changes in patients with NeP of broad aetiology.     

Familial Hemiplegic Migraine: A New Case

SYNOPSIS
The definition of familial hemiplegic migraine is still unsettled. We report the case of a young man who has had hemiplegic migraine attacks for ten years. CT of the brain was abnormal with a low density in the temporal lobe, suggesting infarction and probably having no relation to the attacks. There was a clear family history of hemiplegic migraine, possibly with the same type of attack. Ergotamine tartrate seemed to be effective in preventing headache. This case challenges the current clinical definition of familial hemiplegic migraine, in that while the attack pattern was hereditary, the hemiplegia occurred as an aura rather than accompanying and outlasting the headache.