Effect of early use of noradrenaline on in-hospital mortality in haemorrhagic shock after major trauma: a propensity-score analysis.

BACKGROUND: The role of vasopressors in trauma-related haemorrhagic shock (HS) remains a matter of debate. They are part of the most recent European recommendations on the management of HS and are regularly used in France. We assessed the effect of early administration of noradrenaline in 24 h mortality of trauma patients in HS, using a propensity-score analysis. METHODS: The study included patients from a multicentre prospective regional trauma registry. HS was defined as transfusion of ≥4 erythrocyte-concentrate units during the first 6 h. Patients with a Glasgow coma scale=3 and pre-hospital traumatic cardiac arrest were excluded. The main outcome measure was in-hospital mortality. The explicative and adjustment variables for the outcome and treatment allocation were predetermined by a Delphi method. The in-hospital mortality of patients with and without early administration of noradrenaline was compared in a propensity-score model, including all predetermined variables. RESULTS: Of 7141 patients in the registry in the study period, 6353 were screened and 518 patients in HS (201 with early noradrenaline use and 317 without) were included and analysed. After propensity-score matching, 100 patients remained in each group, and the hazard-ratio mortality was 0.95 (95% confidence interval: 0.45-2.01; P=0.69). CONCLUSIONS: The results of the present study suggest that noradrenaline use in the early phase of traumatic HS does not seem to affect mortality adversely. This observation supports a rationale for equipoise in favour of a prospective trial of the use of vasopressors in HS after trauma.

[Medical information system (PMSI) does not adequately identify severe trauma]. / La codification PMSI identifie mal les traumatismes graves.

BACKGROUND: Resource allocation to hospitals is highly dependent on appropriate case coding. For trauma victims, the major diagnosis-coding category (DCC) is multiple trauma (DCC26), which triggers higher funding. We hypothesized that DCC26 has limited capacity for appropriate identification of severe trauma victims. METHODS: We studied Injury Severity Score (ISS), Trauma Related Injury Severity Score (TRISS) and in-hospital mortality using data recorded in three level 1 trauma centers over a 2-year period. Patients were divided into two groups: DCC26 and non-DCC26. For non-DCC26 patients, two subgroups were identified: patients with severe head trauma and patients with spinal trauma. Clinical endpoints were mortality, ISS>15 and TRISS, IGS II. Use of hospital resources was estimated using funding and expenditures associated with each patient. RESULTS: During the study period, 2570 trauma victims were included in the analysis. These patients were 39±18 years old, with median ISS=14, and observed mortality=10 %. Group DCC26 had 811 (31 %) patients, group non-DCC26 1855 (69 %) patients. DCC26 coding identified a more severely injured group of patients. However, in the group non-DCC26, there was a high proportion of severe trauma (ISS>15: 35 %; TRISS<0.95: 9 %). CONCLUSION: DCC26 is not an appropriate coding for severe trauma patients. For these patients, expenditures will include intensive care and rare and costly resources. We propose to take into account the TRISS score to improve trauma coding.

Early Results of Physician Modified Fenestrated Stent Grafts for the Treatment of Thoraco-abdominal Aortic Aneurysms.

OBJECTIVES: The aim was to determine whether physician modified stent grafts (PMSGs) are safe and effective for the treatment of high risk patients with thoraco-abdominal aortic aneurysms (TAAAs). DESIGN: This was a retrospective single institution study. MATERIAL: Consecutive patients with TAAA undergoing endovascular repair using a PMSG between January 2012 and June 2014 were evaluated. METHODS: Fenestrations to preserve branch vessels were created in TX2 thoracic (Cook Medical) stent grafts. Pre- intra- and post-operative data were recorded by means of a prospectively maintained database. RESULTS: Eleven high risk patients with TAAA (type I, n = 4; type III, n = 3; type IV, n = 3; type V, n = 1) underwent fenestrated endovascular repair using PMSGs. Indications were painful aneurysm (n = 5), >70 mm rapidly enlarging aneurysm (n = 4), saccular aneurysm (n = 1), and visceral patch false aneurysm after open repair of a type IV TAAA (n = 1). In four asymptomatic patients, an additional fenestration was created for temporary selective sac perfusion and occluded 2-4 weeks later. Median duration for stent graft modifications was 2 hours (range 1-3 hours). The median number of fenestrations was three (range 2-4). One patient died during the post-operative period from colonic ischemia, giving a 9% in hospital mortality rate. Four (36%) patients presented with moderate to severe complications. One (9%) patient presented with a paraparesis that resolved completely after spinal fluid drainage. Among surviving patients, four required early endovascular re-intervention for type III endoleak (n = 2), type Ia endoleak (n = 1), or target vessel cannulation failure (n = 1). The median follow up time was 6 months (range 3-20 months). During follow up, no other complications occurred and all target vessels remained patent. One patient presented with a persistent type II endoleak. CONCLUSION: PMSGs provided acceptable short-term results and may be a management option for the treatment of TAAA in selected high risk patients. Durability concerns need to be assessed in additional studies with long-term follow up.

Gate-induced transition between metal-type and thermally activated transport in self-catalyzed MBE-grown InAs nanowires.

Electronic transport properties of InAs nanowires are studied systematically. The nanowires are grown by molecular beam epitaxy on a SiOx-covered GaAs wafer, without using foreign catalyst particles. Room-temperature measurements revealed relatively high resistivity and low carrier concentration values, which correlate with the low background doping obtained by our growth method. Transport parameters, such as resistivity, mobility, and carrier concentration, show a relatively large spread that is attributed to variations in surface conditions. For some nanowires the conductivity has a metal-type dependence on temperature, i.e. decreasing with decreasing temperature, while other nanowires show the opposite temperature behavior, i.e. temperature-activated characteristics. An applied gate voltage in a field-effect transistor configuration can switch between the two types of behavior. The effect is explained by the presence of barriers formed by potential fluctuations.

[Embolization of splenic artery aneurysms: Treatment of choice. About a case and review of the literature]. / Embolisation des anévrysmes de l'artère splénique : traitement de choix. À propos d'un cas et revue de la littérature.

Splenic artery aneurysms constitute 60% of digestive artery aneurysms. They are often discovered incidentally and by imaging. Currently, endovascular treatment is considered the first-line treatment, as it is less invasive with less morbidity and mortality than surgery. An aggressive approach in their management is certainly justified because the overall mortality of ruptured splenic aneurysms is 25%. False splenic aneurysms have a greater potential for rupture than true aneurysms because they grow faster. Endovascular treatment is generally indicated for aneurysms larger than 2cm or with an increase in size of more than 0.5cm/year. Embolization is rarely associated with an infarction of the spleen due to the good supply of short gastric vessels. Embolization is performed using different materials including coils, which can be used alone or with other embolic agents. Post-embolization syndrome can be seen with persistent pain, fever and other systemic symptoms. Endovascular treatment compared to open surgery is associated with better quality of life and appears to be the most cost-effective strategy. Endovascular treatment and especially coil embolization are starting to be the standard treatment. Surgical and laparoscopic treatment are reserved for ruptured aneurysms which are burdened with significant mortality, especially in pregnant women. We report the case of a 66-year-old female patient in whom a splenic artery aneurysm was discovered incidentally during an ultrasound for an ovarian cyst.

Neuroergonomic and psychometric evaluation of full-face crew oxygen masks respiratory tolerance: a proof-of-concept study.

INTRODUCTION: Preventing in-flight hypoxia in pilots is typically achieved by wearing oxygen masks. These masks must be as comfortable as possible to allow prolonged and repeated use. The consequences of mask-induced facial contact pressure have been extensively studied, but little is known about mask-induced breathing discomfort. Because breathlessness is a strong distractor and engages cerebral resources, it could negatively impact flying performances. METHODS: Seventeen volunteers (age 20-32) rated respiratory discomfort while breathing with no mask and with two models of quick-donning full-face crew oxygen masks with regulators (mask A, mask B). Electroencephalographic recordings were performed to detect a putative respiratory-related cortical activation in response to inspiratory constraint (experiment 1, n=10). Oxygen consumption was measured using indirect calorimetry (experiment 2, n=10). RESULTS: With mask B, mild respiratory discomfort was reported significantly more frequently than with no mask or mask A (experiment 1: median respiratory discomfort on visual analogue scale 0.9 cm (0.5-1.4), experiment 1; experiment 2: 2 cm (1.7-2.9)). Respiratory-related cortical activation was present in 1/10 subjects with no mask, 1/10 with mask A and 6/10 with mask B (significantly more frequently with mask B). Breathing pattern, sigh frequency and oxygen consumption were not different. CONCLUSIONS: In a laboratory setting, breathing through high-end aeronautical full-face crew oxygen masks can induce mild breathing discomfort and activate respiratory-related cortical networks. Whether or not this can occur in real-life conditions and have operational consequences remains to be investigated. Meanwhile, respiratory psychometric and neuroergonomic approaches could be worth integrating to masks development and evaluation processes.

CARE-rCortex: A Matlab toolbox for the analysis of CArdio-REspiratory-related activity in the Cortex.

BACKGROUND: Although cardio-respiratory (CR) system is generally controlled by the autonomic nervous system, interactions between the cortex and these primary functions are receiving an increasing interest in neurosciences. NEW METHOD: In general, the timing of such internally paced events (e.g. heartbeats or respiratory cycles) may display a large variability. For the analysis of such CR event-related EEG potentials, a baseline must be correctly associated to each cycle of detected events. The open-source toolbox CARE-rCortex provides an easy-to-use interface to detect CR events, define baselines, and analyse in time-frequency (TF) domain the CR-based EEG potentials. RESULTS: CARE-rCortex provides some practical tools to detect and validate these CR events. Users can define baselines time-locked to a phase of respiratory or heart cycle. A statistical test has also been integrated to highlight significant points of the TF maps with respect to the baseline. We illustrate the use of CARE-rCortex with the analysis of two real cardio-respiratory datasets. COMPARISON WITH EXISTING METHODS: Compared to other open-source toolboxes, CARE-rCortex allows users to automatically detect CR events, to define and check baselines for each detected event. Different baseline normalizations can be used in the TF analysis of EEG epochs. CONCLUSIONS: The analysis of CR-related EEG activities could provide valuable information about cognitive or pathological brain states. CARE-rCortex runs in Matlab as a plug-in of the EEGLAB software, and it is publicly available at https://github.com/FannyGrosselin/CARE-rCortex.

How useful are hemoglobin concentration and its variations to predict significant hemorrhage in the early phase of trauma? A multicentric cohort study.

BACKGROUND: The diagnostic value of hemoglobin (Hb) for detecting a significant hemorrhage (SH) in the early phase of trauma remains controversial. The present study aimed to assess the abilities of Hb measurements taken at different times throughout trauma management to identify patients with SH. METHODS: All consecutive adult trauma patients directly admitted to six French level-1 trauma centers with at least one prehospital Hb measurement were analyzed. The abilities of the following variables to identify SH (≥ 4 units of red blood cells in the first 6 h and/or death related to uncontrolled bleeding within 24 h) were determined and compared to that of shock index (SI): Hb as measured with a point-of-care (POC) device by the prehospital team on scene (POC-Hbprehosp) and upon patient's admission to the hospital (POC-Hbhosp), the difference between POC-Hbhosp and POC-Hbprehosp (DeltaPOC-Hb) and Hb as measured by the hospital laboratory on admission (Hb-Labhosp). RESULTS: A total of 6402 patients were included, 755 with SH and 5647 controls (CL). POC-Hbprehosp significantly predicted SH with an area under ROC curve (AUC) of 0.72 and best cutoff values of 12 g/dl for women and 13 g/dl for men. POC-Hbprehosp < 12 g/dl had 90% specificity to predict of SH. POC-Hbhosp and Hb-Labhosp (AUCs of 0.92 and 0.89, respectively) predicted SH better than SI (AUC = 0.77, p < 0.001); best cutoff values of POC-Hbhosp were 10 g/dl for women and 12 g/dl for men. DeltaPOC-Hb also predicted SH with an AUC of 0.77, a best cutoff value of - 2 g/dl irrespective of the gender. For a same prehospital fluid volume infused, DeltaPOC-Hb was significantly larger in patients with significant hemorrhage than in controls. CONCLUSIONS: Challenging the classical idea that early Hb measurement is not meaningful in predicting SH, POC-Hbprehosp was able, albeit modestly, to predict significant hemorrhage. POC-Hbhosp had a greater ability to predict SH when compared to shock index. For a given prehospital fluid volume infused, the magnitude of the Hb drop was significantly higher in patients with significant hemorrhage than in controls.

Organization in response to massive afflux of war victims in civilian practice - experimental feedback from the November 2015 Paris terrorist attacks.

The arrival of a large number of war-weapon casualties at a civilian trauma center requires anticipation. A plan defining the management principles and the respective roles of the involved physicians and nurses and their interaction with each other is essential. Uni-directional patient flow associated with adequate numbers of staff physicians and nurses under the leadership of a medical director is essential to prevent the overwhelming of the trauma center. Routine and regular interaction between the pre-hospital medical flow control system and the medical director, on one hand, and between surgical teams and the medical director, on the other, are necessary to know when to apply "damage control" surgical techniques. Based on the feedback of a level 1 trauma center that received 53 victims of the November 13, 2015 terrorist attack in Paris, we present the factors of success, and the stumbling blocks.

Riemannian Geometry Applied to Detection of Respiratory States From EEG Signals: The Basis for a Brain-Ventilator Interface.

GOAL: During mechanical ventilation, patient-ventilator disharmony is frequently observed and may result in increased breathing effort, compromising the patient's comfort and recovery. This circumstance requires clinical intervention and becomes challenging when verbal communication is difficult. In this study, we propose a brain-computer interface (BCI) to automatically and noninvasively detect patient-ventilator disharmony from electroencephalographic (EEG) signals: a brain-ventilator interface (BVI). METHODS: Our framework exploits the cortical activation provoked by the inspiratory compensation when the subject and the ventilator are desynchronized. Use of a one-class approach and Riemannian geometry of EEG covariance matrices allows effective classification of respiratory states. The BVI is validated on nine healthy subjects that performed different respiratory tasks that mimic a patient-ventilator disharmony. RESULTS: Classification performances, in terms of areas under receiver operating characteristic curves, are significantly improved using EEG signals compared to detection based on air flow. Reduction in the number of electrodes that can achieve discrimination can be often desirable (e.g., for portable BCI systems). By using an iterative channel selection technique, the common highest order ranking, we find that a reduced set of electrodes (n = 6) can slightly improve for an intrasubject configuration, and it still provides fairly good performances for a general intersubject setting. CONCLUSION: Results support the discriminant capacity of our approach to identify anomalous respiratory states, by learning from a training set containing only normal respiratory epochs. SIGNIFICANCE: The proposed framework opens the door to BVIs for monitoring patient's breathing comfort and adapting ventilator parameters to patient respiratory needs.

[Preoperative cardiac assessment using dobutamine stress echocardiography]. / Evaluation du risque cardiaque avant chirurgie programmée par l'échocardiographie dobutamine.

Postoperative myocardial ischaemia is the leading cause of life expectancy impairment after high cardiac risk surgical procedures. Preoperative identification of patients at high risk for such complication helps reducing its postoperative incidence through therapeutic adjustments. The former relies upon preoperative selection of patients who are candidates for cardiac testing using dobutamine stress echocardiography, according to ACC/AHA guidelines. This exam evaluates echographic myocardial response to a pharmacological stress induced by dobutamine infusion. Its aim is to reproduce part of the stress the myocardium will undergo during surgical procedure. A stress induced myocardial ischaemia suggests such a complication could occur postoperatively. A positive dobutamine stress echocardiography justifies to prescribe preoperative anti-ischaemic treatment in order to reduce the cardiac risk of the further surgical procedure. Moreover, it justifies clear definition of perioperative haemodynamic objectives. Whatever the result of the dobutamine stress echocardiography, cardiac ischaemia should be monitored up to the third postoperative day on the basis of a daily 12-lead electrocardiogram recording and daily plasmatic troponin Ic measurement.

Studies of ACTH secretion control in 116 cases of Cushing's syndrome.

Plasma ACTH (normal value: 0.16 plus or minus mU/100 ml) was measured in 116 patients with Cushing's syndrome, using a bioassay including dynamic tests and sequential determinations. In 10 patients with adrenal tumors ACTH levels were nondetectable (ND) or low, and usually nonstimulatable. In 10 patients with ectopic ACTH secretion high levels (0.42 plus or minus 0.07 mU/100 ml) were measured. The extracts of 6 tumors yielded an ACTH-like substance. Forty-three patients with Cushing's disease (without pituitary tumor) had, before treatment, a mean ACTH level of 0.18 plus or minus 0.01 mU/100 ml, accompanied by high levels of plasma cortisol (32.1 plus or minus 1.9 mug/100 ml). Irregular nycthemeral variations occurred. ACTH rose to 0.30 mU/100 ml after incomplete adrenalectomy (20 patients) and to 1.14 mU/100 ml after total adrenalectomy (21 patients). Dexamethasone (8 mg per day) suppressed ACTH levels. Metyrapone induced a normal ACTH rise, but at abnormal times. Lysine-vasopressin (LVP) induced an ACTH mean relative increase of 120% before, and of 140% after adrenalectomy (i.e., within the normal range). Six nonadrenalectomized patients with pituitary tumors showed similar abnormalities of ACTH regulation. However, the ACTH rise after LVP was above 500%. When pituitary tumors occurred after adrenalectomy (12 patients) the mean basal ACTH level was 18 mU/100 ml. Dexamethasone induced a 90% decrease, and LVP a 416% increase in ACTH levels. In 6 patients with nodular adrenal hyperplasia, ACTH was undetectable before treatment. After adrenalectomy, ACTH rose to 0.4 mU/100 ml (11 patients) and the increase after LVP was 90%. Five additional patients developed pituitary tumors. These data confirm the abnormalities of ACTH feedback regulation in Cushing's disease. However, even when pituitary tumors occur, ACTH levels can be altered by metyrapone, dexamethasone and LVP. This last test is of particular interest for the detection of pituitary tumors. The follow-up pattern of treated nodular adrenal hyperplasia appears to be very similar to that of Cushing's disease.

Development and standardization of methods to evaluate the antibody response to an HIV-1 candidate vaccine in secretions and sera of seronegative vaccine recipients.

Enzyme-linked immunosorbent assays (ELISA) were developed to test, in serum and mucosal samples, total IgG, total IgA, serum albumin, and anti-gp120 MN and anti-p24 LAI IgG and IgA levels. These ELISAs were optimized according to reagents and experimental conditions. Inter- and intra-assay coefficients of variation ranged from 3.3% to 18.6%. The ELISA results were linear and precise, and for anti-HIV-1 IgG and IgA, the analytical recovery was close to 100%. For IgG and IgA titration against gp120 MN and p24 LAI, standards were made using pooled sera or gammaglobulins with assigned titres in ELISA units per ml (EU/ml). These standards were used to obtain a linear regression curve that could then be used to obtain the titres of experimental samples. The cut-offs for positivity were determined for sera and mucosal fluid using healthy controls. Validation conditions were defined for ELISAs, and samples that did not satisfy these conditions were retested. Measurement of total IgG and IgA allowed normalization and comparison of the results of specific immunoglobulin levels between different samples. Serum albumin was tested as a marker of transudation from serum to mucosal fluid, allowing calculation of the relative coefficient of excretion, which is one element required to determine the origin of the immunoglobulin detected in mucosal samples. These ELISAs were developed with samples from HIV-1-infected and healthy subjects. We now have the tools to study and understand mucosal immunity in seronegative subjects vaccinated with an HIV-1 candidate vaccine.

IgG subclass distribution in serum and various mucosal fluids of HIV type 1-infected subjects.

We measured total IgG1, IgG2, IgG3, and IgG4 concentrations by ELISA in serum (S), total saliva (TS), cervicovaginal secretions (CVS), seminal secretions (SPE), and rectal secretions (RS) from either CDC II/III HIV-1-infected subjects or healthy volunteers. Human serum albumin was measured in parallel to calculate the relative coefficient of excretion (RCE). Levels of IgG1 and IgG3 directed against gp120 MN also were measured by ELISA in all samples, and the specific activity (SA) calculated. HIV-1-specific IgG2 and IgG4 were not compared, as total IgG2 and total IgG4 levels in HIV-1-infected subjects were found to be lower than in the healthy controls. Despite substantial interindividual variability, total IgG1 and IgG3 concentrations in all fluids were greater in the HIV-1-infected subjects than in the healthy controls. Calculations of RCE indicated predominantly a transudative origin for IgG subclasses in the different mucosal fluids, except for CVS, in which IgG1, IgG2, and IgG4 was produced locally. The transduction behavior of IgG3 in secretions appears to be different from that of other IgG subclasses. HIV-1-infected subjects were considered positive for IgG1 and IgG3 antibodies against gp120 MN if their antibody levels exceeded the maximum titer measured in the control group. Positive levels of anti-gp120 MN IgG1 were detected for 100% of HIV-1-infected individuals in S, CVS, and SPE, 97% in TS, and 75% in RS. Fewer subjects had positive levels of IgG3 to gp120 MN in their secretions (maximum 67% in CVS). Despite the low concentrations of total IgG3, mean SA values for IgG3 to gp120 MN were greater in secretions than in serum. No significant difference in the SA values for IgG1 to gp120 MN was observed between the different fluids. Only CVS had a local production of HIV-specific IgG1 Our results highlight the importance of an HIV-specific IgG1 and IgG3 immune response in mucosal fluids from HIV-1-infected subjects.

Comparison of the distribution of IgG and IgA antibodies in serum and various mucosal fluids of HIV type 1-infected subjects.

We compared IgG and IgA distribution in serum, three different salivary samples, two different rectal secretion samples, cervicovaginal secretions, and seminal secretions from asymptomatic CDC stage II/III HIV-1-infected subjects (n = 44) and from HIV-1-seronegative volunteers (n = 52). In-house ELISAs were used to measure total IgG and total IgA levels, as well as HIV-specific anti-gp120 MN and anti-p24 LAI IgG and IgA. Human serum albumin was titrated in parallel to calculate the relative coefficient of excretion (RCE). In spite of substantial interindividual variability, total IgG concentrations in all fluids were found to be significantly greater in the HIV-1-infected group than in the seronegative subjects. Calculation of RCE values revealed three different types of mucosal secretion: secretions with no local Ig production, such as sperm; secretions with local production of IgA and transudative origin of IgG, such as salivary and rectal samples; and secretions with local production of both IgG and IgA, such as in cervicovaginal secretions. For all mucosal specimens from HIV-1-infected subjects, the response to HIV-1 was predominantly IgG, with highest titers observed in cervicovaginal secretions (although these were lower than serum levels). In contrast, the specific IgA response appeared weaker in the mucosa than in serum.

Safety and immunogenicity of a live recombinant canarypox virus expressing HIV type 1 gp120 MN MN tm/gag/protease LAI (ALVAC-HIV, vCP205) followed by a p24E-V3 MN synthetic peptide (CLTB-36) administered in healthy volunteers at low risk for HIV infection. AGIS Group and L'Agence Nationale de Recherches sur Le Sida.

A live recombinant canarypox vector expressing HIV-1 gpl20 MN tm/gag/protease LAI (ALVAC-HIV, vCP205) alone or boosted by a p24E-V3 MN synthetic peptide (CLTB-36) was tested in healthy volunteers at low risk for HIV infection for their safety and immunogenicity. Both antigens were well tolerated. ALVAC-HIV (vCP205) induced low levels of neutralizing antibodies against HIV-1 MN in 33% of the volunteers. None of them had detectable neutralizing antibodies against a nonsyncytium-inducing HIV-1 clade B primary isolate (Bx08). After the fourth injection of vCP205, CTL activity was detected in 33% of the volunteers and was directed against Env, Gag, and Pol. This activity was mediated by both CD4+ and CD8+ lymphocytes. On the other hand, the CLTB-36 peptide was poorly immunogenic and induced no neutralizing antibodies or CTLs. Although the ALVAC-HIV (vCP205) and CLTB-36 prime-boost regimen was not optimal, further studies with ALVAC-HIV (vCP205) are warranted because of its clear induction of a cellular immune response and utility as a priming agent for other subunit antigens such as envelope glycoproteins, pseudoparticles, or new peptides.

Postoperative pulmonary complications updating.

Postoperative pulmonary complications (PPCs) are a major contributor to the overall risk of surgery. PPCs affect the length of hospital stay and are associated with a higher in-hospital mortality. PPCs are even the leading cause of death either in cardiothoracic surgery but also in non-cardiothoracic surgery. Thus, reliable PPCs risk stratification tools are the key issue of clinical decision making in the perioperative period. When the risk is clearly identified related to the patient according the ARISCAT score and/or the type of surgery (mainly thoracic and abdominal), low-cost preemptive interventions improve outcomes and new strategies can be developed to prevent this risk. The EuSOS, PERISCOPE and IMPROVE studies demonstrated this care optimization by risk identification first, then risk stratification and new care (multifaceted) strategies implementation allowing a decrease in PPCs mortality by optimizing the clinical path of the patient and the care resources.