Long-term follow-up of cardiac arrest survivors: Protocol of the DESAC (Devenir des survivants d'Arrets Cardiaques) study, a French multicentric prospective cohort.

Background: While the short-term prognosis of cardiac arrest patients - nearly 250,000 new cases per year in Europe - has been extensively studied, less is known regarding the mid and long-term outcome of survivors. Objective: The aim of the DESAC study is to describe mid- and long-term survival rate and functional status of cardiac arrest survivors, and to assess the influence of pre and intra hospital therapeutic strategies on these two outcomes. Methods: Between Jul 2015 and Oct 2018, adult patients over 18 years who were discharged alive from any intensive care units (public and private hospitals) in the Ile-de-France area (Paris and suburbs, France) after a non-traumatic cardiac arrest were screened for participation in this multicentric study. Survivors were included after they signed (or the proxies) an informed consent before discharge during initial hospitalisation. We calculated that including 600 patients in total would allow an 80% power to demonstrate a 2 years survival rate difference of 10% between patients who did and those who did not receive therapeutic hypothermia after resuscitation. Pre- and in-hospital data related to the circumstances surrounding the event and to the therapeutic interventions (such as cardio-pulmonary resuscitation, defibrillation, emergent coronary revascularization, neuroprotective therapeutics) were collected. After discharge, patients were interviewed at 3 months, 6 months and every year thereafter for a minimum follow-up of 26 months and a maximum follow-up of 48 months. Information on vital status, occurrence of cardiovascular events, medications and a comprehensive assessment of the functional status (qualitive of life as assessed by the Short-Form General Health Survey (SF36) scale, activities of daily living (ADL) scale, neurological Cerebral Performance Categories (CPC) and Overall Performance Categories (OPC) scales, socio-professional activities) were collected at follow-up interviews. Discussion: The DESAC study should provide important information regarding several dimensions of the mid and long-term prognosis of cardiac arrest survivors and on the benefit (and potentially harm) of early therapeutic strategies.

Collective excitations in a melt of fast phase change material GeCu2Te3.

Inelastic x-ray scattering measurements have been carried out to investigate atomic dynamics in a melt of fast phase change material GeCu2Te3. The dynamic structure factor was analysed using the model function with three damped harmonic oscillator components. By investigating the correlation between the excitation energy and the linewidth, and that between the excitation energy and the intensity on contour maps of a relative approximate probability distribution function proportional toexp(-χ2/N), we could judge the reliability of each inelastic excitation in the dynamic structure factor. The results indicate that there are two inelastic excitation modes besides the longitudinal acoustic one in the liquid. The lower energy excitation could be assigned to the transverse acoustic one whereas the higher energy one disperses like fast sound. The latter result may imply that the liquid ternary alloy exhibits a microscopic phase separation tendency.

Ten-year follow-up of Lenke 5 curves treated with spinal fusion.

INTRODUCTION: Patients with surgically treated Lenke 5 curves require at least partial fusion of the lumbar spine. The implications of lumbar fusion remain unknown as long-term follow-up is sparse. METHODS: A retrospective review of a prospectively collected registry of patients with Lenke 5 curves treated with spinal fusion was performed. Clinical and radiographic outcomes as well as SRS-22 scores were collected at 2- and 10-year follow-up. RESULTS: 54 of 247 available patients met all inclusion criteria [26 treated with posterior spinal fusion (PSF) and 28 with anterior spinal fusion (ASF)]. Preoperative lumbar curve magnitude was 45.1 ± 8.4° and corrected to 14.0 ± 7.2° (p < 0.001). A 3.3 ± 7.3° increase in curve size was noted at final follow-up (p < 0.008) with 20.3% of patients having a loss of correction (LOC)of 10° or more. Thoracic curve correction and kyphosis were stable at 10-year follow-up. End vertebrae angulation improved from 11.2 ± 23.2° to 0.96 ± 6.4° (p = 0.004) and translation improved from 2.5 ± 2.9 to 0.92 ± 1.5 cm (p = 0.008) with no LOC. Disc wedging below the lower instrumented vertebrae increased from 0.3 ± 4.9° to 2.8 ± 4.4° (p < 0.001) with no change at 10 years. SRS-22 self-image and satisfaction improved from post-operative to final follow-up. No patient required a second operation. CONCLUSIONS: Both ASF and PSF showed durable results at 10-year follow-up with no obvious difference between approaches. 20% of patients had a LOC > 10°; this did not correlate with pain or need for revision surgery. Disc wedging was stable. Selection of LIV did not correlate with pain scores. LEVEL OF EVIDENCE: Level III.

Ischemic injury of the upper gastrointestinal tract after out-of-hospital cardiac arrest: a prospective, multicenter study.

BACKGROUND: The consequences of cardiac arrest (CA) on the gastro-intestinal tract are poorly understood. We measured the incidence of ischemic injury in the upper gastro-intestinal tract after Out-of-hospital CA (OHCA) and determined the risk factors for and consequences of gastrointestinal ischemic injury according to its severity. METHODS: Prospective, non-controlled, multicenter study in nine ICUs in France and Belgium conducted from November 1, 2014 to November 30, 2018. Included patients underwent an esophago-gastro-duodenoscopy 2 to 4 d after OHCA if still intubated and the presence of ischemic lesions of the upper gastro-intestinal tract was determined by a gastroenterologist. Lesions were a priori defined as severe if there was ulceration or necrosis and moderate if there was mucosal edema or erythema. We compared clinical and cardiac arrest characteristics of three groups of patients (no, moderate, and severe lesions) and identified variables associated with gastrointestinal ischemic injury using multivariate regression analysis. We also compared the outcomes (organ failure during ICU stay and neurological status at hospital discharge) of the three groups of patients. RESULTS: Among the 214 patients included in the analysis, 121 (57%, 95% CI 50-63%) had an upper gastrointestinal ischemic lesion, most frequently on the fundus. Ischemic lesions were severe in 55/121 (45%) patients. In multivariate regression, higher adrenaline dose during cardiopulmonary resuscitation (OR 1.25 per mg (1.08-1.46)) was independently associated with increased odds of severe upper gastrointestinal ischemic lesions; previous proton pump inhibitor use (OR 0.40 (0.14-1.00)) and serum bicarbonate on day 1 (OR 0.89 (0.81-0.97)) were associated with lower odds of ischemic lesions. Patients with severe lesions had a higher SOFA score during the ICU stay and worse neurological outcome at hospital discharge. CONCLUSIONS: More than half of the patients successfully resuscitated from OHCA had upper gastrointestinal tract ischemic injury. Presence of ischemic lesions was independently associated with the amount of adrenaline used during resuscitation. Patients with severe lesions had higher organ failure scores during the ICU stay and a worse prognosis. Clinical Trial Registration NCT02349074 .

[Hepatopulmonary syndrome: Prevalence, pathophysiology and clinical implications]. / Syndrome hépatopulmonaire : prévalence, physiopathologie et implications cliniques.

Hepatopulmonary syndrome (HPS) is a pulmonary vascular disease induced by portal hypertension that is characterized by dilation of the pulmonary capillaries and right-to-left shunting, leading to gas exchange abnormalities. While dysregulation of several endothelial cell (EC)-derived angiocrine factors and the development of HPS have been associated, the field is currently lacking in mechanistic understanding on how they contribute to disease initiation, perpetuation, and worsening. Although substantial progress has been made in the description of clinical characteristics and outcomes, no specific targeting therapy has been shown to have a long-term effect on the evolution of HPS; only liver transplantation can lead full or partial reversibility of the syndrome. This article aims to provide a comprehensive review of the clinical and epidemiological definitions of HPS and to describe its experimental models as well as recent advances in understanding the pathophysiology of the disease, with specific focus on BMP-9 and its signaling pathway.

Differences in ebullitive methane release from small, shallow ponds present challenges for scaling.

Small, shallow waterbodies are potentially important sites of greenhouse gas release to the atmosphere. The role of ebullition may be enhanced here relative to larger and deeper systems, due to their shallow water, but these features remain relatively infrequently studied in comparison to larger systems. Herein, we quantify ebullitive release of methane (CH4) in small shallow ponds in three regions of North America and investigate the role of potential drivers. Shallow ponds exhibited open-water season ebullitive CH4 release rates as high as 40 mmol m-2 d-1, higher than previously reported for similar systems. Ebullitive release of CH4 varied by four orders of magnitude across our 15 study sites, with differences in flux rates both within and between regions. What is less clear are the drivers responsible for these differences. There were few relationships between open water-season ebullitive flux and physicochemical characteristics, including organic matter, temperature, and sulphate. Temperature was only weakly related to ebullitive CH4 release across the study when considering all observation intervals. Only four individual sites exhibited significant relationships between temperature and ebullitive CH4 release. Other sites were unresponsive to temperature, and region-specific factors may play a role. There is some evidence that where surface water sulphate concentrations are high, CH4 production and release may be suppressed. Missouri sites (n = 5) had characteristically low ebullitive CH4 release; here bioturbation could be important. While this work greatly expands the number of open-water season ebullition rates for small and shallow ponds, more research is needed to disentangle the role of different drivers. Further investigation of the potential thresholding behaviour of sulphate as a control on ebullitive CH4 release in lentic systems is one such opportunity. What is clear, however, is that efforts to scale emissions (e.g., as a function of temperature) must be undertaken with caution.

Biodistribution of Detonation Synthesis Nanodiamonds in Mice after Intravenous Administration and Some Biochemical Changes in Blood Plasma.

Biodistribution of nanodiamonds in mice after intravenous administration, activities of AST and ALT, and the level of bilirubin in the blood plasma were studied in 2.5 h and 10, 35, and 97 days after injection of nanodiamonds. In 2.5 h after intravenous injection, nanodiamonds mainly accumulate in the lungs and liver. Then, redistribution of nanodiamonds from all organs to the liver was observed. Activities of AST and ALT and the level of bilirubin in the blood increased after 2.5 h and then decreased to the initial values.

Low energy excitation in liquid Sb and liquid Bi observed in inelastic x-ray scattering spectra.

The dynamic structure factorS(Q,E), whereQandEare momentum and energy transfer, respectively, has been measured for liquid Sb, using inelastic x-ray scattering. A modified damped harmonic oscillator model function was applied to analyseS(Q,E) of liquid Sb and also to that of liquid Bi by Inuiet al(2015Phys. Rev.B92, 054206). The obtained excitation energy was in fairly good agreement with that predicted byab initiomolecular dynamics simulations on these liquid semi-metals. The excitation energy of the longitudinal acoustic mode in liquid Sb and liquid Bi exhibits flat-toppedQdependence whereas the lower excitation energy below the longitudinal acoustic excitation showsQ-gap behaviour. From the viscosity estimated from theQ-gap experimentally obtained, it is inferred that the lower energy excitation arises from the transverse acoustic excitation in the liquids.

Risk factors for surgical site infection after pancreatic surgery: a better postoperative antibiotic strategy is possible.

INTRODUCTION: Pancreatic surgery is associated with high morbidity, mainly due to infectious complications, so many centres use postoperative antibiotics (ATBpo) for all patients. However, antibiotic regimens vary according to local practices. The aims of this study were to describe the occurrence of surgical site infection (SSI) and ATBpo prescription after pancreatic surgery, and to determine the risk factors of postoperative SSI, in order to better define the clinical indications for ATBpo in this context. PATIENTS AND METHODS: All patients undergoing scheduled major pancreatic surgery from January 2007 to November 2018 were included in this retrospective study. Patients were classified into four groups according to SSI and routine ATBpo prescription: SSI+/ATBpo+, SSI-/ATBpo+, SSI+/ATBpo- and SSI-/ATBpo-. In addition, risk factors (fever and pre-operative biliary prosthesis) associated with the occurrence of SSI and ATBpo were analysed using a logistic regression model. RESULTS: Data from 149 patients (115 pancreaticoduodenectomies and 34 splenopancreatectomies) were analysed. Thirty (20.1%) patients experienced SSI and 42 (28.2%) received ATBpo. No difference was found in routine ATBpo prescription between patients with and without SSI (26.7% vs 28.6%, respectively; P=0.9). Amongst the 107 patients who did not receive routine ATBpo, 85 (79.4%) did not develop an SSI. In-hospital mortality did not differ between infected and uninfected patients (7% vs 2%, respectively; P=0.13). The occurrence of postoperative fever differed between SSI+ and SSI- patients (73.3% vs 34.2%, respectively; P<0.001), while the prevalence of pre-operative biliary prosthesis was similar (37.9% vs 26.7%, respectively; P=0.3). CONCLUSION: Non-routine ATBpo after major pancreatic surgery resulted in 85 (56%) patients being spared unnecessary antibiotic treatment. This suggests that routine ATBpo prescription could be excessive, but further studies are needed to confirm such antibiotic stewardship. Fever appears to be a relevant clinical sign for individual-based prescription, but the presence of a biliary prosthesis does not.

Nematic Correlation Length in Iron-Based Superconductors Probed by Inelastic X-Ray Scattering.

Nematicity is ubiquitous in electronic phases of high-T_{c} superconductors, particularly in the Fe-based systems. We used inelastic x-ray scattering to extract the temperature-dependent nematic correlation length ξ from the anomalous softening of acoustic phonon modes in FeSe, underdoped Ba(Fe_{0.97}Co_{0.03})_{2}As_{2}, and optimally doped Ba(Fe_{0.94}Co_{0.06})_{2}As_{2}. In all cases, we find that ξ is well described by a power law (T-T_{0})^{-1/2} extending over a wide temperature range. Combined with the previously reported Curie-Weiss behavior of the nematic susceptibility, these results point to the mean-field character of the nematic transition, which we attribute to a sizable nematoelastic coupling that is likely detrimental to superconductivity.

Systematic review and literature appraisal on methodology of conducting and reporting critical-care echocardiography studies: a report from the European Society of Intensive Care Medicine PRICES expert panel.

BACKGROUND: The echocardiography working group of the European Society of Intensive Care Medicine recognized the need to provide structured guidance for future CCE research methodology and reporting based on a systematic appraisal of the current literature. Here is reported this systematic appraisal. METHODS: We conducted a systematic review, registered on the Prospero database. A total of 43 items of common interest to all echocardiography studies were initially listed by the experts, and other "topic-specific" items were separated into five main categories of interest (left ventricular systolic function, LVSF n = 15, right ventricular function, RVF n = 18, left ventricular diastolic function, LVDF n = 15, fluid management, FM n = 7, and advanced echocardiography techniques, AET n = 17). We evaluated the percentage of items reported per study and the fraction of studies reporting a single item. RESULTS: From January 2000 till December 2017 a total of 209 articles were included after systematic search and screening, 97 for LVSF, 48 for RVF, 51 for LVDF, 36 for FM and 24 for AET. Shock and ARDS were relatively common among LVSF articles (both around 15%) while ARDS comprised 25% of RVF articles. Transthoracic echocardiography was the main echocardiography mode, in 87% of the articles for AET topic, followed by 81% for FM, 78% for LVDF, 70% for LVSF and 63% for RVF. The percentage of items per study as well as the fraction of study reporting an item was low or very low, except for FM. As an illustration, the left ventricular size was only reported by 56% of studies in the LVSF topic, and half studies assessing RVF reported data on pulmonary artery systolic pressure. CONCLUSION: This analysis confirmed sub-optimal reporting of several items listed by an expert panel. The analysis will help the experts in the development of guidelines for CCE study design and reporting.

Antitumor activity of ipatasertib combined with chemotherapy: results from a phase Ib study in solid tumors.

BACKGROUND: This phase Ib study evaluated the safety, tolerability, pharmacokinetics, and preliminary efficacy of the oral AKT inhibitor ipatasertib and chemotherapy or hormonal therapy in patients with advanced or metastatic solid tumors to determine combined dose-limiting toxicities (DLTs), maximum tolerated dose, and recommended phase II doses and schedules. PATIENTS AND METHODS: The clinical study comprised four combination treatment arms: arm A (with docetaxel), arm B [with mFOLFOX6 (modified leucovorin, 5-fluorouracil, and oxaliplatin)], arm C (with paclitaxel), and arm D (with enzalutamide). Primary endpoints were safety and tolerability; secondary endpoints were pharmacokinetics, clinical activity per Response Evaluation Criteria in Solid Tumors v1.1, and prostate-specific antigen levels. RESULTS: In total, 122 patients were enrolled. Common adverse events were diarrhea, nausea, vomiting, decreased appetite, and fatigue. The safety profiles of the combination regimens were consistent with those of the background regimens, except for diarrhea, hyperglycemia, and rash, which were previously observed with ipatasertib treatment. The only combination DLT across all treatment arms was one event of grade 3 dehydration (ipatasertib 600 mg and paclitaxel). Recommended phase II doses for ipatasertib were 600 mg (and mFOLFOX6) and 400 mg (and paclitaxel), respectively. The maximum assessed dose of ipatasertib 600 mg combined with docetaxel or enzalutamide was well tolerated. Coadministration with enzalutamide (a cytochrome P450 3A inducer) resulted in approximately 50% lower ipatasertib exposure. CONCLUSIONS: Ipatasertib in combination with chemotherapy or hormonal therapy was well tolerated with a safety profile consistent with that of ATP-competitive AKT inhibitors. CLINICAL TRIAL NUMBER: NCT01362374.

[Cor pulmonale]. / Cœur pulmonaire.

Cor pulmonale is a disease of the heart characterised by dilatation of the right ventricle and paradoxical movement of the interventricular septum. The diagnosis depends on echocardiography even if pulmonary artery catheterisation suggests it. It is secondary to pulmonary disease or a disorder of the pulmonary circulation. These two mechanisms, which are often connected, involve pulmonary hypertension as the origin of a systolic and diastolic overload of the right ventricle, which then leads to the alterations of its structure and performance. Acute cor pulmonale is usually secondary to an acute respiratory distress syndrome or to a pulmonary embolism but it can also be seen in primary lactic acidosis, a vaso-occlusive crisis in a patient with sickle cell anaemia, severe acute asthma, and entry of air or injected crushed tablets into the circulation. Chronic cor pulmonale is the terminal stage of pulmonary hypertension. Clinically these patients are dyspnoeic with signs of chronic right heart failure. They should have an echocardiogram confirming the cardiac involvement. Certain precipitating factors, such as infection of any origin, have been reported, leading to acute on chronic cor pulmonale that has a particularly high mortality.

Peculiar temperature dependence of dynamical sound speed in liquid Se50Te50 by inelastic x-ray scattering.

Inelastic x-ray scattering (IXS) measurements were carried out on liquid Se50Te50 at temperatures up to 1323 K to investigate how the atomic dynamics changes with temperature through the semiconductor-metal transition. The acoustic mode was clearly observed in the dynamic structure factor and its energy was determined using a damped harmonic oscillator model. The dynamical sound speed obtained by IXS for [Formula: see text] nm-1 was found to behave similarly to the temperature dependence of ultrasonic sound velocity with a minimum near the semiconductor metal transition. The results can be explained by taking liquid Se50Te50 to be an inhomogeneous liquid consisting of metallic and semiconducting domains whose size is approximately 3 nm. The relaxation time obtained from frequency dependence of the dynamical sound speed was on a picosecond time scale.

Vaccinia-based oncolytic immunotherapy Pexastimogene Devacirepvec in patients with advanced hepatocellular carcinoma after sorafenib failure: a randomized multicenter Phase IIb trial (TRAVERSE).

Pexastimogene devacirepvec (Pexa-Vec) is a vaccinia virus-based oncolytic immunotherapy designed to preferentially replicate in and destroy tumor cells while stimulating anti-tumor immunity by expressing GM-CSF. An earlier randomized Phase IIa trial in predominantly sorafenib-naïve hepatocellular carcinoma (HCC) demonstrated an overall survival (OS) benefit. This randomized, open-label Phase IIb trial investigated whether Pexa-Vec plus Best Supportive Care (BSC) improved OS over BSC alone in HCC patients who failed sorafenib therapy (TRAVERSE). 129 patients were randomly assigned 2:1 to Pexa-Vec plus BSC vs. BSC alone. Pexa-Vec was given as a single intravenous (IV) infusion followed by up to 5 IT injections. The primary endpoint was OS. Secondary endpoints included overall response rate (RR), time to progression (TTP) and safety. A high drop-out rate in the control arm (63%) confounded assessment of response-based endpoints. Median OS (ITT) for Pexa-Vec plus BSC vs. BSC alone was 4.2 and 4.4 months, respectively (HR, 1.19, 95% CI: 0.78-1.80; p = .428). There was no difference between the two treatment arms in RR or TTP. Pexa-Vec was generally well-tolerated. The most frequent Grade 3 included pyrexia (8%) and hypotension (8%). Induction of immune responses to vaccinia antigens and HCC associated antigens were observed. Despite a tolerable safety profile and induction of T cell responses, Pexa-Vec did not improve OS as second-line therapy after sorafenib failure. The true potential of oncolytic viruses may lie in the treatment of patients with earlier disease stages which should be addressed in future studies. ClinicalTrials.gov: NCT01387555.

SEIS: Insight's Seismic Experiment for Internal Structure of Mars.

By the end of 2018, 42 years after the landing of the two Viking seismometers on Mars, InSight will deploy onto Mars' surface the SEIS (Seismic Experiment for Internal Structure) instrument; a six-axes seismometer equipped with both a long-period three-axes Very Broad Band (VBB) instrument and a three-axes short-period (SP) instrument. These six sensors will cover a broad range of the seismic bandwidth, from 0.01 Hz to 50 Hz, with possible extension to longer periods. Data will be transmitted in the form of three continuous VBB components at 2 sample per second (sps), an estimation of the short period energy content from the SP at 1 sps and a continuous compound VBB/SP vertical axis at 10 sps. The continuous streams will be augmented by requested event data with sample rates from 20 to 100 sps. SEIS will improve upon the existing resolution of Viking's Mars seismic monitoring by a factor of ∼ 2500 at 1 Hz and ∼ 200 000 at 0.1 Hz. An additional major improvement is that, contrary to Viking, the seismometers will be deployed via a robotic arm directly onto Mars' surface and will be protected against temperature and wind by highly efficient thermal and wind shielding. Based on existing knowledge of Mars, it is reasonable to infer a moment magnitude detection threshold of M w ∼ 3 at 40 ∘ epicentral distance and a potential to detect several tens of quakes and about five impacts per year. In this paper, we first describe the science goals of the experiment and the rationale used to define its requirements. We then provide a detailed description of the hardware, from the sensors to the deployment system and associated performance, including transfer functions of the seismic sensors and temperature sensors. We conclude by describing the experiment ground segment, including data processing services, outreach and education networks and provide a description of the format to be used for future data distribution. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11214-018-0574-6) contains supplementary material, which is available to authorized users.

Correction to: Practical approach to diastolic dysfunction in light of the new guidelines and clinical applications in the operating room and in the intensive care.

In the original article [1], the authors noticed a typographical error in Figure 2. The top left box should have included "E/A <0.8 and E <50 cm/s". Please see below the corrected figure.