Do institutions matter for citizens' health status? Empirical evidence from Italy.

This paper investigates the role of institutional quality in explaining cross-regional variation in population health status in Italy. We first introduce a composite Regional Health Status Indicator summarizing life expectancy, mortality and morbidity data. Then, we study the empirical relationship between this indicator and a set of socioeconomic, health system and institutional controls at the Italian regional level over the period of 2011-2019. We find that institutional quality is a driver of population health. Furthermore, well-functioning local institutions and regions compliant with national standards in terms of public healthcare services (Essential Levels of Care) make socioeconomic context no longer relevant for population health, potentially reducing inequalities.

Development and validation of a comprehensive model to predict complications after hepatectomy.

OBJECTIVE: Despite advances in perioperative care, hepatectomy remains associated with morbidity rates of up to 40%. Currently, available nomograms for predicting severe post-hepatectomy complications do not include early postoperative data. This retrospective observational study aimed to determine whether the parameters routinely measured in patients admitted to the Intensive Care Unit (ICU) after hepatectomy could represent risk factors for severe morbidity and to propose a nomogram scoring system to predict severe postoperative complications. PATIENTS AND METHODS: 411 adult patients who underwent elective hepatectomy at a high-volume tertiary care center for hepatic surgery from December 2016 to June 2022 were enrolled. The primary outcome was the assessment of predictors of 30-day severe postoperative complications following hepatectomy, defined as Clavien-Dindo grade 3a or higher. As a secondary outcome, we aimed to develop an easy-to-use scoring system to estimate the risk of severe postoperative complications. RESULTS: Severe complications occurred in 78 patients (19%). The final model included body mass index, preoperative bilirubin level, and ICU data (i.e., pH, lactate clearance, arterial lactate concentration 12 hours after ICU admission, need for packed red blood cell transfusions, and length of stay). Notably, the latter three variables were proven to be independent predictors of the outcomes. The model showed an overall good fit (C-index=0.754, corrected Dxy=0.692). A calibration plot using bootstrap internal validity resampling confirmed the stability of the model (mean absolute error=0.017, root mean square error of approximation=0.00051). CONCLUSIONS: We developed an accurate and practical scoring system based on preoperative and early postoperative data to predict poor outcomes after hepatectomy. Further external validation on larger series could lead to the integration of such a tool in the routine clinical practice to support patients' management and early warning during ICU stay. Graphical Abstract: https://www.europeanreview.org/wp/wp-content/uploads/Graphical-Abstract-NEW-2.pdf.

Pilot randomized experimental study evaluating isopropyl alcohol and ultraviolet-C radiation in the disinfection of healthcare workers' smartphones.

BACKGROUND: Smartphones in medical settings pose infection risks due to harbouring pathogenic bacteria. AIM: This pilot study assessed the effectiveness duration of sanitization methods, focusing on 70% isopropyl alcohol wipes and ultraviolet-C (UVC) boxes, aiming to obtain preliminary data on the reduction in total bacterial load 3 h post-sanitization. METHODS: A randomized monocentric trial with two intervention arms (wipes and UVC boxes) was designed. As participants, healthcare workers from three wards at Fondazione Policlinico Universitario 'A. Gemelli' IRCCS Hospital were recruited, stratified by ward, and block randomized within each ward to control confounders. FINDINGS: Seventy-one healthcare workers, mostly nurses (62%) were included in the study. Initial bacterial load reduction was significant with both disinfection techniques, but after 3 h both methods showed increased bacterial levels, with wipes displaying potentially higher residual efficacy (P=0.056). To adequately size a trial (89% power, significance level 0.05) for assessing the residual efficacy of alcohol-impregnated wipes compared with UVC boxes at 3 h post-sanitization, 503 professionals per group were required. CONCLUSION: This study highlights the necessity for guidelines on hospital smartphone sanitization and educational initiatives for healthcare workers and patients. Further studies, adequately sized, are necessary to determine optimal sanitization intervals and assess pathogen transmission risks.

Comparative bench study evaluation of a modified snorkeling mask used during COVID-19 pandemic and standard interfaces for non-invasive ventilation.

PURPOSE: The aim of this bench study is to compare the standard NIV and nCPAP devices (Helmet, H; Full face mask, FFM) with a modified full face snorkeling mask used during COVID-19 pandemic. METHODS: A mannequin was connected to an active lung simulator. The inspiratory and expiratory variations in airways pressure observed with a high simulated effort, were determined relative to the preset CPAP level. NIV was applied in Pressure Support Mode at two simulated respiratory rates and two cycling-off flow thresholds. During the bench study, we measured the variables defining patient-ventilator interaction and performance. RESULTS: During nCPAP, the tested interfaces did not show significant differences in terms of ∆Pawi and ∆Pawe. During NIV, the snorkeling mask demonstrated a better patient-ventilator interaction compared to FFM, as shown by significantly shorter Pressurization Time and Expiratory Trigger Delay (p < 0.01), but no significant differences were found in terms of Inspiratory Trigger Delay and Time of Synchrony between the interfaces tested. At RR 20sim, the snorkeling mask presented the lower ΔPtrigger (p < 0.01), moreover during all the conditions tested the snorkeling mask showed the longer Pressure Time Product at 200, 300, and 500 ms compared to FFM (p < 0.01). A major limitation of snorkeling mask is that during NIV with this interface it is possible to reach maximum 18 cmH2O of peak inspiratory pressure. CONCLUSIONS: The modified snorkeling mask can be used as an acceptable alternative to other interfaces for both nCPAP and NIV in emergencies.

Awake prone positioning in nonintubated spontaneous breathing ICU patients with acute hypoxemic respiratory failure (PRONELIFE)-protocol for a randomized clinical trial.

BACKGROUND: It is uncertain whether awake prone positioning can prevent intubation for invasive ventilation in spontaneous breathing critically ill patients with acute hypoxemic respiratory failure. Awake prone positioning could benefit these patients for various reasons, including a reduction in direct harm to lung tissue, and prevention of tracheal intubation-related complications. DESIGN AND METHODS: The PRONELIFE study is an investigator-initiated, international, multicenter, randomized clinical trial in patients who may need invasive ventilation because of acute hypoxemic respiratory failure. Consecutive patients admitted to participating ICUs are randomly assigned to standard care with awake prone positioning, versus standard care without awake prone positioning. The primary endpoint is a composite of tracheal intubation and all-cause mortality in the first 14 days after enrolment. Secondary endpoints include time to tracheal intubation and effects of awake prone positioning on oxygenation parameters, dyspnea sensation, and complications. Other endpoints are the number of days free from ventilation and alive at 28 days, total duration of use of noninvasive respiratory support, total duration of invasive ventilation, length of stay in ICU and hospital, and mortality in ICU and hospital, and at 28, 60, and 90 days. We will also collect data regarding the tolerance of prone positioning. DISCUSSION: The PRONELIFE study is among the first randomized clinical trials investigating the effect of awake prone positioning on intubation rate in ICU patients with acute hypoxemic failure from any cause. The PRONELIFE study is sufficiently sized to determine the effect of awake prone positioning on intubation for invasive ventilation-patients are eligible in case of acute hypoxemic respiratory failure without restrictions regarding etiology. The PRONELIFE study is a pragmatic trial in which blinding is impossible-however, as around 35 ICUs worldwide will participate in this study, its findings will be highly generalizable. The findings of the PRONELIFE study have the potential to change clinical management of patients who may need invasive ventilation because of acute hypoxemic respiratory failure. TRIAL REGISTRATION: ISRCTN ISRCTN11536318 . Registered on 17 September 2021. The PRONELIFE study is registered at clinicaltrials.gov with reference number NCT04142736 (October, 2019).

Thermodynamic Stability Implies Causality.

The stability conditions of a relativistic hydrodynamic theory can be derived directly from the requirement that the entropy should be maximized in equilibrium. Here, we use a simple geometrical argument to prove that, if the hydrodynamic theory is stable according to this entropic criterion, then localized perturbations to the equilibrium state cannot propagate outside their future light cone. In other words, within relativistic hydrodynamics, acausal theories must be thermodynamically unstable, at least close to equilibrium. We show that the physical origin of this deep connection between stability and causality lies in the relationship between entropy and information. Our result may be interpreted as an "equilibrium conservation theorem," which generalizes the Hawking-Ellis vacuum conservation theorem to finite temperature and chemical potential.

VMAT-like plans for magnetic resonance guided radiotherapy: Addressing unmet needs.

PURPOSE: VMAT delivery technique is currently not applicable to Magnetic Resonance-guided radiotherapy (MRgRT) hybrid systems. Aim of this study is to evaluate an innovative VMAT-like (VML) delivery technique. MATERIAL AND METHODS: First, planning and dosimetric evaluation of the MRgRT VML treatment have been performed on 10 different disease sites and the results have been compared with the corresponding IMRT plans. Then, in the second phase, 10 of the most dosimetrically challenging locally advanced pancreas treatment plans have been retrospectively re-planned using the VML approach to explore the potentiality of this new delivery technique. Finally, VML robustness was evaluated and compared with the IMRT plans, considering a lateral positioning error of ± 5 mm. RESULTS: In phase one, all VML plans were within constraint for all OARs. When PTV coverage is considered, in the 50% of the cases VML PTV coverage is equal or higher than in IMRT plan. In the remaining 50%, the highest target under coverage difference in comparison with IMRT plan is -1.71%. The mean and maximum treatment time differences (VML-IMRT) is 0.2 min and 3.1 min respectively. In phase two, the treatment time variation (VML-IMRT), shows a mean, maximum and minimum variations of 1.3, 4.6 and -0.6 min respectively. All VML plans have a better target coverage if compared with IMRT plans, keeping in any case the OARs constraints within tolerance. VML doesn't increase plan robustness. CONCLUSION: VMAT-like treatment approach appeared to be an efficient planning solution and it was decided to clinically implement it in daily practice, especially in the frame of hypo fractionated treatments.

Optimal symptom combinations to aid COVID-19 case identification: Analysis from a community-based, prospective, observational cohort.

OBJECTIVES: Diagnostic work-up following any COVID-19 associated symptom will lead to extensive testing, potentially overwhelming laboratory capacity whilst primarily yielding negative results. We aimed to identify optimal symptom combinations to capture most cases using fewer tests with implications for COVID-19 vaccine developers across different resource settings and public health. METHODS: UK and US users of the COVID-19 Symptom Study app who reported new-onset symptoms and an RT-PCR test within seven days of symptom onset were included. Sensitivity, specificity, and number of RT-PCR tests needed to identify one case (test per case [TPC]) were calculated for different symptom combinations. A multi-objective evolutionary algorithm was applied to generate combinations with optimal trade-offs between sensitivity and specificity. FINDINGS: UK and US cohorts included 122,305 (1,202 positives) and 3,162 (79 positive) individuals. Within three days of symptom onset, the COVID-19 specific symptom combination (cough, dyspnoea, fever, anosmia/ageusia) identified 69% of cases requiring 47 TPC. The combination with highest sensitivity (fatigue, anosmia/ageusia, cough, diarrhoea, headache, sore throat) identified 96% cases requiring 96 TPC. INTERPRETATION: We confirmed the significance of COVID-19 specific symptoms for triggering RT-PCR and identified additional symptom combinations with optimal trade-offs between sensitivity and specificity that maximize case capture given different resource settings.

Household disinfectant exposure during the COVID-19 pandemic: a retrospective study of the data from an Italian poison control center.

OBJECTIVE: Since the beginning of the COVID-19 pandemic it has been recommended that chemical disinfectants are used to protect surfaces. This study aimed to determine whether the number of exposure calls related to household disinfectants (HD) received between January 30, 2020 to May 18, 2020 varied from the same time period in the previous year. MATERIALS AND METHODS: A retrospective review of the poison control center database from the Fondazione Universitario Policlinico Agostino Gemelli IRCCS, Rome, Italy, was conducted. Calls from Italian citizens, hospitals, and general practitioners received during the same time period in 2019 and 2020 were compared. RESULTS: The center received 1972 exposure calls during the study period. A 5% increase in calls regarding exposure to HDs was noted from 2019 to 2020 (9.8% to 15.2%, p<0.001). The majority of enquiries regarded bleach-containing products, hand sanitizers, ethanol, and hydrogen peroxide. Most calls were received from patients in their homes (n, 259; prevalence, 86%; increase, 107%) and concerned accidental exposure (n, 280; prevalence, 93%; increase, 76%), while cases of intentional exposure decreased (n, 14; prevalence, 5%; decrease, 33%). The main route of exposure was ingestion (n, 170; prevalence, 57%; increase, 45%), but the highest increase was observed in inhalation cases (n, 82; prevalence, 27%; increase, 122%). CONCLUSIONS: As the incidence of enquiries regarding products that can represent an important health hazard, when improperly used, increased in 2020 suggests that the COVID-19 public health messaging on the proper use of HDs should be improved.

Association between colorectal cancer and Streptococcus gallolyticus subsp. pasteuranus (former S. bovis) endocarditis: clinical relevance and cues for microbiota science. Case report and review of the literature.

OBJECTIVE: The purpose of this paper is to contextualize the case of a patient with a synchronous diagnosis of colorectal cancer (CRC) and endocarditis from S. gallolyticus subsp. pasteuranus (former S. Bovis) within the current evidence, in order to determine if this condition is indicative of an underlying CRC and if it has any pathophysiologic significance. PATIENTS AND METHODS: First, we describe the clinical case. Then, we review the literature focused on the association between infections from the former S. Bovis group and CRC and on the possible role of certain microbiota species on the occurrence of CRC. At last, we discuss the implications of this case considering the current evidence. RESULTS: There is a strong association between all the species of the former S. Bovis group and CRC. There is initial evidence that these bacteria may contribute to CRC by a genomic passenger mechanism. CONCLUSIONS: There are two main conclusions for this paper. The first one is that CRC neoplasms and endocarditis from all species of the former S. bovis group have a strong association. Any case of infection by these subspecies should prompt to a diagnostic completion by colonoscopy. The second one is that there is an increased need for detailed reports/series and original articles based on the evaluation of gut microbiota in patients with CRC, with the aim to clarify if the association between bacteria and CRC is causative or sporadic and to better understand the possible causative mechanism of specific bacteria in initiating and promoting CRC.

Optimal symptom combinations to aid COVID-19 case identification: analysis from a community-based, prospective, observational cohort.

OBJECTIVES: Diagnostic work-up following any COVID-19 associated symptom will lead to extensive testing, potentially overwhelming laboratory capacity whilst primarily yielding negative results. We aimed to identify optimal symptom combinations to capture most cases using fewer tests with implications for COVID-19 vaccine developers across different resource settings and public health. METHODS: UK and US users of the COVID-19 Symptom Study app who reported new-onset symptoms and an RT-PCR test within seven days of symptom onset were included. Sensitivity, specificity, and number of RT-PCR tests needed to identify one case (test per case [TPC]) were calculated for different symptom combinations. A multi-objective evolutionary algorithm was applied to generate combinations with optimal trade-offs between sensitivity and specificity. FINDINGS: UK and US cohorts included 122,305 (1,202 positives) and 3,162 (79 positive) individuals. Within three days of symptom onset, the COVID-19 specific symptom combination (cough, dyspnoea, fever, anosmia/ageusia) identified 69% of cases requiring 47 TPC. The combination with highest sensitivity (fatigue, anosmia/ageusia, cough, diarrhoea, headache, sore throat) identified 96% cases requiring 96 TPC. INTERPRETATION: We confirmed the significance of COVID-19 specific symptoms for triggering RT-PCR and identified additional symptom combinations with optimal trade-offs between sensitivity and specificity that maximize case capture given different resource settings.

Thromboelastography clot strength profiles and effect of systemic anticoagulation in COVID-19 acute respiratory distress syndrome: a prospective, observational study.

OBJECTIVE: Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection may yield a hypercoagulable state with fibrinolysis impairment. We conducted a single-center observational study with the aim of analyzing the coagulation patterns of intensive care unit (ICU) COVID-19 patients with both standard laboratory and viscoelastic tests. The presence of coagulopathy at the onset of the infection and after seven days of systemic anticoagulant therapy was investigated. PATIENTS AND METHODS: Forty consecutive SARS-CoV-2 patients, admitted to the ICU of a University hospital in Italy between 29th February and 30th March 2020 were enrolled in the study, providing they fulfilled the acute respiratory distress syndrome criteria. They received full-dose anticoagulation, including Enoxaparin 0.5 mg·kg-1 subcutaneously twice a day, unfractionated Heparin 7500 units subcutaneously three times daily, or low-intensity Heparin infusion. Thromboelastographic (TEG) and laboratory parameters were measured at admission and after seven days. RESULTS: At baseline, patients showed elevated fibrinogen activity [rTEG-Ang 80.5° (78.7 to 81.5); TEG-ACT 78.5 sec (69.2 to 87.9)] and an increase in the maximum amplitude of clot strength [FF-MA 42.2 mm (30.9 to 49.2)]. No alterations in time of the enzymatic phase of coagulation [CKH-K and CKH-R, 1.1 min (0.85 to 1.3) and 6.6 min (5.2 to 7.5), respectively] were observed. Absent lysis of the clot at 30 minutes (LY30) was observed in all the studied population. Standard coagulation parameters were within the physiological range: [INR 1.09 (1.01 to 1.20), aPTT 34.5 sec (29.7 to 42.2), antithrombin 97.5% (89.5 to 115)]. However, plasma fibrinogen [512.5 mg·dl-1 (303.5 to 605)], and D-dimer levels [1752.5 ng·ml-1 (698.5 to 4434.5)], were persistently increased above the reference range. After seven days of full-dose anticoagulation, average TEG parameters were not different from baseline (rTEG-Ang p = 0.13, TEG-ACT p = 0.58, FF-MA p = 0.24, CK-R p = 0.19, CKH-R p  = 0.35), and a persistent increase in white blood cell count, platelet count and D-dimer was observed (white blood cell count p < 0.01, neutrophil count p = 0.02, lymphocyte count p < 0.01, platelet count p = 0.13 < 0.01, D-dimer levels p= 0.02). CONCLUSIONS: SARS-CoV-2 patients with acute respiratory distress syndrome show elevated fibrinogen activity, high D-dimer levels and maximum amplitude of clot strength. Platelet count, fibrinogen, and standard coagulation tests do not indicate a disseminated intravascular coagulation. At seven days, thromboelastographic abnormalities persist despite full-dose anticoagulation.

Efficacy of Telavancin in Comparison to Linezolid in a Porcine Model of Severe Methicillin-Resistant Staphylococcus aureus Pneumonia.

Current guidelines recommend vancomycin and linezolid as first-line agents against methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. Telavancin is a potential new therapeutic alternative, specifically in monomicrobial MRSA pneumonia. This study compared the efficacies of telavancin versus linezolid in a porcine model of severe MRSA pneumonia. In 18 mechanically ventilated pigs (32.11 ± 1.18 kg), 75 ml of 106 CFU/ml of MRSA was administered into each pulmonary lobe. After the onset of pneumonia, pigs were randomized into three groups: a control group, a group receiving 22.5 mg/kg of body weight every 24 h (q24h) of telavancin, and a group receiving 10 mg/kg q12h of linezolid intravenously. Tracheal aspirate and bronchoalveolar lavage (BAL) fluids were cultured every 24 h. After 48 h of treatment, tissue samples were collected from the ventral and dorsal sections of each lobe. Microbiological and histopathological analyses were performed. Lung tissue concentrations differed among the groups (P = 0.019), with the lowest MRSA lung burden in the telavancin group (P < 0.05 versus the control). MRSA was detected in 46.7%, 40.0%, and 21.7% of the lung tissue samples from the control, linezolid, and telavancin groups, respectively (P < 0.001). MRSA concentrations differed among the groups in tracheal aspirate fluid (P = 0.011) but not in BAL fluid. Furthermore, there was no increased risk of kidney injury during telavancin use. Thus, telavancin has higher bactericidal efficacy than linezolid during the first 48 h of treatment in a porcine model of severe MRSA pneumonia. However, studies are needed to confirm the benefits of telavancin in treating MRSA nosocomial pneumonia.

Major trauma critical pathway: preliminary results from the monitoring system in the regional network and in a hub center in Rome metropolitan area.

OBJECTIVE: The aim of this study is to collect the two years' data regarding the Integrated Trauma Management System (SIAT) by capturing the activity of its three Hubs in the Italian Lazio Region and test the performance of one of the Hubs' (Fondazione Policlinico Universitario A. Gemelli - IRCCS, FPG -IRCCS) Major Trauma Clinical Pathway's (MTCP) monitoring system, introducing the preliminary results through volume, process and outcome indicators. MATERIALS AND METHODS: A retrospective analysis on SIAT was conducted on years 2016 to 2018, by collecting outcome and timeliness indicators through the Lazio Informative System whereas the MTCP was monitored through set of indicators from the FPG - IRCCS Informative System belonging to randomly selected clinical records of the established period. RESULTS: Hubs managed 11.3% of the 998,240 patients admitted in SIAT. All patients eligible for MTCP were "Flagged", and 83% underwent a CT within 2 hours; intra-hospital mortality was 13% whereas readmission rates 16.9%. CONCLUSIONS: SIAT converges the most severe patients to its Hubs. The MTCP monitoring system was able to measure a total of 9 out of 13 indicators from the original panel. This research may serve as a departing point to conduct a pre-post analysis on the performance of the MTCP.

Fetal heart rate variability responsiveness to maternal stress, non-invasively detected from maternal transabdominal ECG.

PURPOSE: Prenatal stress (PS) during pregnancy affects in utero- and postnatal child brain-development. Key systems affected are the hypothalamic-pituitary-adrenal axis and the autonomic nervous system (ANS). Maternal- and fetal ANS activity can be gauged non-invasively from transabdominal electrocardiogram (taECG). We propose a novel approach to assess couplings between maternal (mHR) and fetal heart rate (fHR) as a new biomarker for PS based on bivariate phase-rectified signal averaging (BPRSA). We hypothesized that PS exerts lasting impact on fHR. METHODS: Prospective case-control study matched for maternal age, parity, and gestational age during the third trimester using the Cohen Perceived Stress Scale (PSS-10) questionnaire with PSS-10 over or equal 19 classified as stress group (SG). Women with PSS-10 < 19 served as control group (CG). Fetal electrocardiograms were recorded by a taECG. Coupling between mHR and fHR was analyzed by BPRSA resulting in fetal stress index (FSI). Maternal hair cortisol, a memory of chronic stress exposure for 2-3 months, was measured at birth. RESULTS: 538/1500 pregnant women returned the questionnaire, 55/538 (10.2%) mother-child pairs formed SG and were matched with 55/449 (12.2%) consecutive patients as CG. Maternal hair cortisol was 86.6 (48.0-169.2) versus 53.0 (34.4-105.9) pg/mg (p = 0.029). At 36 + 5 weeks, FSI was significantly higher in fetuses of stressed mothers when compared to controls [0.43 (0.18-0.85) versus 0.00 (- 0.49-0.18), p < 0.001]. CONCLUSION: Prenatal maternal stress affects the coupling between maternal and fetal heart rate detectable non-invasively a month prior to birth. Lasting effects on neurodevelopment of affected offspring should be studied. TRIAL REGISTRATION: Clinical trial registration: NCT03389178.

Madelung's disease and acute alcoholic hepatitis: case report and review of literature.

Madelung's disease is a rare condition characterized by symmetric growth of fatty tumors (lipomas) around the neck, shoulders, upper arms, and trunk. It often affects men with a history of alcohol abuse. Here we report a review of the literature about this disease together with the description of a patient affected by Madelung's disease and acute alcoholic hepatitis.

Is the social status a new prognostic factor in the Fournier's gangrene?

Fournier's gangrene is a life-threatening acute necrotizing fasciitis of perianal, genitourinary and perineal areas. Local symptoms are scrotal swelling, erythema of scrotal skin and pain with generalized constitutional symptoms. The gangrene may extends to abdominal wall, intra-abdominal structures, and even in the retroperitoneal tissues. Urgent surgical debridement is crucial to warrant a good outcome since delayed intervention carries a poor prognosis. We report the case of a not diabetic patient with Fournier's disease presented with severe sepsis and successfully treated with urgent deep debridement and reconstructive surgery. We propose the social status of the patient as a prognostic factor with high impact for survival rate.

Assessing the role of CAP for more sustainable and healthier food systems in Europe: A literature review.

Today, the European food system is characterized by unhealthy dietary trends, environmentally unsustainable production, and a dependency on an ageing farming population. The ongoing reform of the Common Agricultural Policy (CAP) represents an opportunity to redress these issues. This literature review highlights trends in how academic and grey literature have received CAP attempts in addressing the (i) environmental issues, (ii) nutritional outcomes, and (iii) rural livelihoods. Additionally, future policy and research directions relating to the CAP have been identified from the selected literature. The reviewed literature varies in approach and perspective. In particular, since the environment and rural development are already part of the CAP, the reviewed studies analyze and propose improvements to existing mechanisms. While for nutrition, the reviewed studies assessed possible policy strategies for integrating this sphere within the CAP, highlighting both the complexity of this task as well as its potential benefits. Despite these differences, a clear commonality emerged from the policy recommendations: the CAP should promote the European Union (EU) policy integration and multi-disciplinary and participatory research as key strategies to meet food system sustainability targets.

Polymyxin B hemoperfusion in endotoxemic septic shock patients without extreme endotoxemia: a post hoc analysis of the EUPHRATES trial.

PURPOSE: The EUPHRATES trial examined the impact of polymyxin B hemoperfusion (PMX) on mortality in patients with septic shock and endotoxemia, defined as EAA ≥ 0.60. No difference was found in 28-day all-cause mortality. However, the trial showed that in some patients with septic shock the burden of endotoxin activity was extreme (EAA ≥ 0.9). In a post hoc analysis, we evaluated the impact of PMX use in patients with septic shock and endotoxin activity measured between 0.6-0.89. METHODS: Post-hoc analysis of the EUPHRATES trial for the 194 patients with EAA ≥ 0.6-0.89 who completed two treatments (PMX or sham). The primary end point was mortality at 28 days adjusted for APACHE II score and baseline mean arterial pressure (MAP). Additional end points included changes in MAP, cumulative vasopressor index (CVI), median EAA reduction, ventilator-free days (VFD), dialysis-free days (DFD) and hospital length of stay. Subpopulations analyzed were site and type of infection and those with norepinephrine dose > 0.1 mcg/kg/min at baseline. RESULTS: At 28 days, 23 patients of 88 (26.1%) in the PMX group died versus 39 of 106 (36.8%) in the sham group [risk difference 10.7%, OR 0.52, 95% CI (0.27, 0.99), P = 0.047]. When unadjusted for baseline variables, P = 0.11. The 28-day survival time in the PMX group was longer than for the sham group [HR 0.56 (95% CI 0.33, 0.95) P = 0.03]. PMX treatment compared with sham showed greater change in MAP [median (IQR) 8 mmHg (- 0.5, 19.5) vs. 4 mmHg (- 4.0, 11) P = 0.04] and VFD [median (IQR) 20 days (0.5, 23.5) vs. 6 days (0, 20), P = 0.004]. There were no significant differences in other end points. There was a significant difference in mortality in PMX-treated patients with no bacterial growth on culture [PMX, 6/30 (20%) vs. sham, 13/31 (41.9%), P = 0.005]. The median EAA change in the population was - 12.9% (range: increase 49.2%-reduction 86.3%). The mortality in the above median EAA change group was PMX: 6/38 (15.7%) vs. sham 15/49 (30.6%), P = 0.08. CONCLUSIONS: These hypothesis-generating results, based on an exploratory post hoc analysis of the EUPHRATES trial, suggest measurable responses in patients with septic shock and an EAA ≥ 0.6 to 0.89 on changes in mean arterial pressure, ventilator-free days and mortality. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01046669. Funding Spectral Medical Incorporated.