A novel risk score for severe ARDS patients undergoing ECMO after retrieval from peripheral hospitals.

BACKGROUND: Extracorporeal Membrane Oxygenation in severe ARDS unresponsive to conventional protective ventilation is associated with elevated costs, resource and complications, and appropriate risk stratification of candidate patients could be useful to recognize those more likely to benefit from ECMO. We aimed to derive a new outcome prediction score for patients retrieved by our ECMO team from peripheral centers, including systematic echocardiographic evaluation before ECMO start. METHODS: Sixty-nine consecutive patients with refractory ARDS requiring ECMO transferred from peripheral centers to our ICU (a tertiary ECMO referral center), from 1 October 2009 to 31 December 2015, were assessed. RESULTS: All patients were transported on ECMO (distance, median 77, range 4-456 km) The mortality rate was 41% (28/69). Our new risk score included age ≥ 42 years, BMI < 31 kg/m2 , RV dilatation, and pH < 7.35. The proposed cut off (Youden's index method) of nine had a sensitivity of 96% and a specificity of 30% (AUC-ROC: 0.85, 95% CI: 0.76-0.94, P < 0.001). When assessing the discriminatory ability of our risk score in the population of local patients, survivors had a mean value of 15.4 ± 8.6, whereas non-survivors showed a mean value of 20.1 ± 7.4 (P < 0.001). CONCLUSIONS: Our new risk score shows good discriminatory ability both in patients retrieved from peripheral centers and in those implanted at our center. This score includes variables easily available at bedside, and, for the first time, a pathophysiologic element, RV dilatation.

Neurophysiological prediction of neurological good and poor outcome in post-anoxic coma.

OBJECTIVE: Investigation of the utility of association between electroencephalogram (EEG) and somatosensory-evoked potentials (SEPs) for the prediction of neurological outcome in comatose patients resuscitated after cardiac arrest (CA) treated with therapeutic hypothermia, according to different recording times after CA. METHODS: Glasgow Coma Scale, EEG and SEPs performed at 12, 24 and 48-72 h after CA were assessed in 200 patients. Outcome was evaluated by Cerebral Performance Category 6 months after CA. RESULTS: Within 12 h after CA, grade 1 EEG predicted good outcome and bilaterally absent (BA) SEPs predicted poor outcome. Because grade 1 EEG and BA-SEPs were never found in the same patient, the recording of both EEG and SEPs allows us to correctly prognosticate a greater number of patients with respect to the use of a single test within 12 h after CA. At 48-72 h after CA, both grade 2 EEG and BA-SEPs predicted poor outcome with FPR=0.0%. When these neurophysiological patterns are both present in the same patient, they confirm and strengthen their prognostic value, but because they also occurred independently in eight patients, poor outcome is predictable in a greater number of patients. SIGNIFICANCE: The combination of EEG/SEP findings allows prediction of good and poor outcome (within 12 h after CA) and of poor outcome (after 48-72 h). Recording of EEG and SEPs in the same patients allows always an increase in the number of cases correctly classified, and an increase of the reliability of prognostication in a single patient due to concordance of patterns.

Pulmonary vascular dysfunction in refractory acute respiratory distress syndrome before veno-venous extracorporeal membrane oxygenation.

BACKGROUND: Pulmonary vascular dysfunction has been described in patients with acute respiratory distress syndrome (ARDS). Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a well-established treatment for these patients. We hypothesized that severe pulmonary vascular dysfunction and cor pulmonale identified by echocardiography before cannulation in these patients were associated with worse survival. METHODS: Echocardiography was used to identify pulmonary hypertension in 21 patients with refractory ARDS just before ECMO implantation. Survival was compared for those with and without cor pulmonale. RESULTS: In our series, the overall mortality rate was 57.1% (12/21). Echocardiographic exams were transthoracic in 5 patients (23.8%), transesophageal in 4 patients (19%), and both (transthoracic and transesophageal) in the remaining 12 patients (57.1%). In our series, six patients (28.5%) showed LV dysfunction. Acute cor pulmonale was detectable in 2 patients (9.5%), while the remaining 19 patients showed moderate pulmonary dysfunction. Survivors had a higher pre-cannulation LV ejection fraction (EF) (P = 0.02) and tricuspid annular plane excursion (P = 0.04), and lower peak systolic pulmonary artery pressures (P = 0.02). CONCLUSIONS: In patients with refractory ARDS immediately before ECMO implantation, the prevalence of acute cor pulmonale is low (9.5%). Survival is associated with higher LVEF and lower systolic pulmonary arterial pressure. These findings support the idea that echocardiographic assessment of pulmonary artery pressure in patients with refractory ARDS before VV-ECMO implantation may have value for risk-stratification.

Cerebral microemboli detected by transcranial doppler in patients treated with extracorporeal membrane oxygenation.

INTRODUCTION: Cerebrovascular complications rate in patients treated with extracorporeal membrane oxygenation (ECMO) is about 7%. Ischemic stroke may be caused by solid or gaseous microemboli due to thrombosis within the circuit or cannula. Transcranial Doppler (TCD) is the only method able to detect microembolic signals (MES) in real time. The objective of this study was to detect possible MES by TCD in patients treated with veno-venous (VV) and veno-arterial (VA) ECMO and to test for a relation between the number of MES and the 6-month clinical outcome of these patients. METHODS: This is a monocentric observational prospective study in patients consecutively admitted and treated with ECMO at our regional ECMO referral center in 18 months. TCD detection of MES was performed in patients upon initiation of treatment and then repeated during treatment. RESULTS: Two hundred and forty-eight TCD monitoring were performed in 42 VV and 11 VA ECMO patients. MES were detected in 26.2% of VV ECMO patients and in 81.8% of VA ECMO patients (P < 0.001). In both subgroups of patients, no correlation was found between MES detection and extracorporeal flow velocities or aPTT values. In VA ECMO patients, an inverse correlation between left ventricular ejection fraction and MES grading was found (P = 0.037). In both groups, no clinical neurological impairments correlated to MES detection were found at 6 months follow-up. CONCLUSIONS: MES were found in both ECMO configurations; independently from their pathophysiology, MES do not seem to influence clinical outcome. Multicenter studies are still required with more extensive cases to confirm these results.

Audits in real time for safety in critical care: definition and pilot study.

UNLABELLED: Adverse events significantly impact upon mortality rates and healthcare costs. PURPOSE: To design a checklist of safety measures based on relevant scientific literature, apply random checklist measures to critically ill patients in real time (safety audits), and determine its utility and feasibility. METHODS: A list of safety measures based on scientific literature was drawn up by investigators. Subsequently, a group of selected experts evaluated these measures using the Delphi methodology. Audits were carried out on 14 days over a period of one month. Each day, 50% of the measures were randomly selected and measured in 50% of the randomized patients. Utility was assessed by measuring the changes in clinical performance after audits, using the variable improvement proportion related to audits. Feasibility was determined by the successful completion of auditing on each of the days on which audits were attempted. RESULTS: The final verified checklist comprised 37 measures distributed into 10 blocks. The improvement proportion related to audits was reported in 83.78% of the measures. This proportion was over 25% in the following measures: assessment of the alveolar pressure limit, checking of mechanical ventilation alarms, checking of monitor alarms, correct prescription of the daily treatment orders, daily evaluation of the need for catheters, enteral nutrition monitoring, assessment of semi-recumbent position, and checking that patient clinical information is properly organized in the clinical history. Feasibility: rounds were completed on the 14 proposed days. CONCLUSIONS: Audits in real time are a useful and feasible tool for modifying clinical actions and minimizing errors.

Pesticides in water and sediments from natural protected areas of Spain and their associated ecological risk.

In the last years, issues related to intensive agriculture have been found in protected areas potentially harming wildlife. This study aimed to analyze a wide range of pesticides in water and sediments of two protected areas namely Doñana Natural Park (DNP) and Tablas de Daimiel National Park (TDNP) performing an environmental risk assessment in order to highlight potential risks to living organisms derived from pesticide burden. Higher pesticide load was found in DNP than TDNP with similar distribution profiles, with pyrethroid insecticides (PYRs) the main detected class. Particularly problematic are two PYRs, cyhalothrin and fenvalerate, which were detected at high concentrations that can pose a high risk to aquatic organisms. In addition, despite being detected at lower concentrations, the presence of chlorpyrifos, cypermethrin, and permethrin in water, and of chlorpyrifos, dicofol, and diflufenican in sediments, must be taken into account due to their potential risks for aquatic organisms. Moreover, some banned pesticides such as dimethoate, terbutryn, diazinon, and tricyclazol were detected in water at levels which deserve further investigation to assess their potential sources, including potential illegal practices.

Effect of mothering on the spatial exploratory behavior of quail chicks.

Previous maternal deprivation experiments demonstrated that absence of maternal care impacts the behavioral development of young animals. Here we assessed the influence of the presence of a mothering hen on the spatial exploration of Japanese quail chicks, after the mothering period. Brooded and nonbrooded chicks were placed in a novel environment containing feeding troughs. The distribution of chicks and their inter-individual distances were measured during repeated tests. Brooded chicks exhibited a higher ability to disperse, thereby progressively exploiting larger surfaces and gaining access to food more easily. The fact that exploration by nonbrooded chicks was delayed suggests a deficit in their exploratory motivation and/or spatial skills. We hypothesize that brooded chicks experienced the constraint to follow the mothering hen, and to adapt to frequent reconfigurations of their environment. The lack of this variability in the environment of nonbrooded chicks could have reduced adaptability of their spatial behavior.

Pesticide contamination of bird species from Doñana National Park (southwestern Spain): Temporal trends (1999-2021) and reproductive impacts.

Doñana National Park (DNP) is a protected area renowned for hosting a wide variety of birds. However, the agricultural practices in its surroundings might cause pesticide contamination of the park biota. This work aimed to assess temporal trends of a wide variety of pesticides, including organochlorine (OCPs), organophosphate (OPPs) and pyrethroid (PYRs) pesticides, in bird eggs collected for more than twenty years (1999-2021) in DNP. Twenty-six pesticides were detected, being 4,4'-DDE the most frequently detected and also the one with the highest concentrations (up to 2.55 µg g-1 ww), exceeding in some cases the values usually reported to cause detrimental health and reproductive effects in avian species. An overall decreasing trend of OCPs was observed. In contrast, an apparent increase in PYRs was detected from 2013 onwards, especially for fenvalerate, whose median concentration was 3-5 orders of magnitude higher in the most recent samples. Moreover, other pesticides such as oxadiazon, oxyfluorfen and fenitrothion were first detected in 2021 samples. Finally, two variables estimating the cumulative impact of pesticides significantly decreased the breeding performance of a top predator such as the booted eagle. Therefore, it is essential to control the use of pesticides in the agricultural practices surrounding DNP and to study their potential negative impact on the bird populations breeding in this protected area.

Pesticides in sediments of the Ebro River Delta cultivated area (NE Spain): Occurrence and risk assessment for aquatic organisms.

Intense agricultural activities are performed in the Ebro River Delta (NE Spain) with extensive use of pesticides. Medium to highly polar pesticides have not been studied intensively in sediments despite its larger use in the recent years. This work aimed at assessing the occurrence of 69 pesticides, including medium to highly polar compounds, in sediments collected from drainage and irrigation channels of the Ebro River Delta during the main rice growing season. In addition, an environmental risk assessment was performed to evaluate the potential adverse effects to sediment-dwelling organisms with the risk quotient approach. A total of 24 pesticides were detected in sediments with bentazone and cypermethrin exhibiting high detection frequencies (79%) as well as high mean concentration levels (61.9 and 81.8 ng g-1 dw, respectively). Overall, the Alfacs bay, in the South of the delta, presented higher pesticide contamination than the Fangar bay, in the North. A similar pesticide distribution profile was observed in both bays, with oxadiazoles, organochlorines, pyrethroids, benzothiazinones and organophosphates as major, predominant classes. The presence of oxadiazon, pendimethalin and thifensulfuron methyl in the sediments may pose a moderate risk to sediment-dwelling organisms while bentazone, chlorpyrifos, and cypermethrin exhibited a potential high risk. Thus, the importance of the inclusion of medium to highly polar pesticides in the analysis of sediments is emphasized since some polar pesticides such as bentazone, imidacloprid, and thifensulfuron-methyl have been detected at concentrations that may pose a risk to aquatic organisms. Moreover, the co-occurrence of pesticides may potentially pose a high risk to sediment-dwelling organisms in 13 out of the 14 investigated locations. Finally, it could be concluded that the risk derived from the presence of pesticides in sediments must be assessed since some pesticides not detected at concerning levels in water, may pose a moderate/high risk in the sediments.

Comparison of physical activity and sedentary behaviours between young haemophilia A patients and healthy adolescents.

In recent studies, adolescent haemophilia A patients and healthy adolescents have been encouraged to participate in physical activity (PA) based on its many established health benefits. However, none of the studies to date has used objective measures of PA and sedentary behaviour. The aims of the current study included: (i) to determine the amount and intensity of habitual PA among haemophilia A and healthy adolescents, and in haemophilia A patients with and without bleeding episodes in the previous year, and (ii) to identify the type and determine the time spent in sedentary activities in which both groups participate to obtain a broadened view of their daily activities. A total of 41 adolescent haemophiliacs and 25 healthy adolescents, between the ages of 8 and 18 years, participated in this cross-sectional study. A triaxial accelerometer was used to measure PA and the Adolescent Sedentary Activity Questionnaire to assess sedentary behaviours among members of both groups. Adolescent haemophilia A patients showed a higher daily mean time engaged in light, moderate and moderate-to-vigorous PAs relative to their healthy counterparts (P < 0.001). Patients who had experienced bleeding episodes during the previous year also spent more time participating in vigorous PAs than healthy adolescents (P = 0.002). With regard to sedentary behaviours, healthy adolescents spent more time listening to music than haemophilia A adolescents (P = 0.003), whereas haemophilia A adolescents spent more time watching TV (P < 0.001) and playing videogames (P = 0.003) than healthy counterparts. Findings suggest that increased participation in moderate intensity PAs and reduced sedentary behaviours should be recommended among adolescents with haemophilia A.

Comparison between single-step and balloon dilatational tracheostomy in intensive care unit: a single-centre, randomized controlled study.

BACKGROUND: Balloon dilatational tracheostomy using the Ciaglia Blue Dolphin device has recently been introduced as a modification of the Ciaglia technique. The aim of this study was to compare the new Dolphin system with the single-step dilatational tracheostomy (Ciaglia Blue Rhino) in intensive care unit (ICU) patients. METHODS: Consecutive patients admitted to the ICU of the Emergency Department (Careggi Teaching Hospital, Florence, Italy) from January 2009 to October 2009, aged >18 years and with an indication for percutaneous dilatational tracheostomy (PDT), were enrolled. Exclusion criteria were infection/injury/malignancy of the neck, thyroid gland hypertrophy, severe head injury with uncontrolled intracranial hypertension, and coagulopathy. Patients were randomly assigned to undergo PDT using either the Ciaglia Blue Rhino (n=35) or the Ciaglia Blue Dolphin technique (n=35). Groups were compared according to tracheal puncture, tracheal tube placement time, procedure-related complications, and bleeding. RESULTS: Baseline clinical data were comparable between the two groups. Median procedure time was significantly shorter in the Rhino group compared with the Dolphin group (1.5 vs 4 min, P = 0.035). The presence of limited intra-tracheal bleeding at bronchoscopy examination after 6 h from PDT was more frequent in the Dolphin group than in the Rhino group patients (68.6% vs 34.3%, respectively, P = 0.008). No major bleeding occurred in either group. CONCLUSIONS: PDT using the Ciaglia Blue Dolphin technique is a feasible and viable option in ICU patients, but the Rhino technique had a shorter execution time and seemed to be associated with fewer tracheal injuries.

The value of lung ultrasound monitoring in H1N1 acute respiratory distress syndrome.

We present the case of a healthy young male who developed acute respiratory failure as a result of infection with influenza A/H1N1 of swine-origin and in whom ventilatory support was optimised and recovery of lung function was monitored by the use of sequential chest ultrasound examinations. The potential pivotal role of bedside lung ultrasonography in H1N1-induced respiratory failure is discussed.

[Does Stewart-Fencl improve the evaluation of acid-base status in stable patients on hemodiafiltration?]. / ¿Mejora la aproximación físico-química de Stewart-Fencl la valoración del equilibrio ácido-base en pacientes estables en hemodiafiltración?

INTRODUCTION: The traditional evaluation of acid-base status relies on the Henderson-Hasselbach equation. In 1983, an alternative approach, based on physical and chemical principles was proposed by P. Stewart. In this approach, plasma pH is determined by 3 independent variables: pCO2, Strong Ion Difference (SIDm), which is the difference between the strong cations (Na +, K +, Ca ++, Mg ++) and the strong anions (Cl-, lactate) and total plasma concentration of nonvolatile weak acids (ATot), mainly inorganic phosphate and albumin. Bicarbonate is considered a dependent variable. The aim of this study was to evaluate the acid-base status using both perspectives, physical chemical and traditional approach. MATERIAL AND METHODS: We studied 35 patients (24 M; 11F) on hemodiafiltration, mean age was 67,2+/-15,7, 8+/-19,2 kg. We analyzed plasma chemistry including pH, pCO2, HCO3-, base excess and Na+, K+, Cl-, Ca++, Mg++, lactate and SIDm. The SID estimated (SIDe) was calculated by Figge's formula (1000 x 2.46E-11 x pCO2 / (10-pH) + Album gr/dl x (0.123 x pH-0.631) + P in mmol/l x (0.309 x pH-0.469) and Gap of the SID as the difference SIDm-SIDe. RESULTS: pH preHD was 7,36+/-0,08 and pH posHD 7,44+/-0,08 (p < 0.001). There was no significant differences between pCO2 pre and pos-HD. HCO3 - and base excess increased during the session (p < 0.001). SIDm decreased from 46,2+/-2,9 preHD to 45+/-2,3 mEq/l postHD (p < 0.05). On the opposite, SIDe increased from 38,5+/-3,8 to 42,9+/-3,1 mEq/l (p < 0.001). The Gap Anion descended from 18,6+/-3,8 preHD to 12,8+/-2,8 mEq/l mEq/l postHD (p < 0.001) and the Gap of the SID 7,6+/-3 to 2,1+/-2 (p < 0.001). Anion Gap correlated with the Gap-SID so much pre-HDF as pos-HDF. Delta Base excess correlated only with Delta of the Gap SID. CONCLUSION: Stewart-Fencl's approach does not improve characterization of acid-base status in patients on chronic HDF. In presence of normocloremia the SIDm does not reflect the alkalinizing process of the session of hemodialysis. According this approach, hemodialysis therapy can be viewed as a withdrawal of inorganic anions, especially the sulphate. These anions are replaced by OH - and secondarily for HCO3-. The approach only improves the evaluation of unmeasured anions by the Gap of the SID, without the effect of albumin and phosphate.

Comprehending and improving cannabis specialized metabolism in the systems biology era.

Cannabis sativa is a source of food, fiber and specialized metabolites such as cannabinoids, with psychoactive and pharmacological effects. Due to its expanding and increasingly-accepted use in medicine, cannabis cultivation is acquiring more importance and less social stigma. Humans initiated different domestication episodes whose later spread gave rise to a plethora of landrace cultivars. At present, breeders cross germplasms from different gene pools depending on their specific use. The fiber (hemp) and drug (marijuana) types of C. sativa differ in their cannabinoid chemical composition phenotype (chemotype) and also in the accumulation of terpenoid compounds that constitute a strain's particular flavor and scent. Cannabinoids are isoprenylated polyketides among which cannabidiolic acid (CBDA) and (-)-trans-Δ9-tetrahydrocannabinol acid (THCA) have been well-documented for their many effects on humans. Here, we review the most studied specialized metabolic pathways in C. sativa, showing how terpenes and cannabinoids share both part of the isoprenoid pathway and the same biosynthetic compartmentalization (i.e. glandular trichomes of leaves and flowers). We enlist the several studies that have deciphered these pathways in this species including physical and genetic maps, QTL analyses and localization and enzymatic studies of cannabinoid and terpene synthases. In addition, new comparative modeling of cannabinoid synthases and phylogenetic trees are presented. We describe the genome sequencing initiatives of several accessions with the concomitant generation of next-generation genome maps and transcriptomic data. Very recently, proteomic characterizations and systems biology approaches such as those applying network theory or the integration of multi-omics data have increased the knowledge on gene function, enzyme diversity and metabolite content in C. sativa. In this revision we drift through the history, present and future of cannabis research and on how second- and third-generation sequencing technologies are bringing light to the field of cannabis specialized metabolism. We also discuss different biotechnological approaches for producing cannabinoids in engineered microorganisms.

Switching from three times a week to short daily online hemodiafiltration: effects on acid-base balance.

AIMS: This study examines the effect of a change from the standard 4-5 hours 3 times a week of online hemodiafiltration (OL-HDF) to 2-2.5 hours daily (6 times a week) OL-HDF, on acid-base balance, and attempts assess the modifications of acid-base parameters, ionic concentration, and electrical charges of albumin and phosphate available for diffusion and convection mechanisms across the membrane and subsequent infusion. METHODS: In 18 patients on online HDF, blood gas, electrolytes (Na, K, Cl), lactate, phosphate, albumin, apparent strong ion difference (SIDa), effective strong ion difference (SIDe), strong ion gap (SIG), anion gap (AG), and bicarbonate and pH time-averaged concentration (TAC) and time-averaged deviation (TAD) variables were evaluated at baseline, and 1, 3, 6, 9, and 12 months after patients were switched to daily OL-HDF. Additionally, in 12 patients, the same parameters measured simultaneously at dialyzer inlet, outlet, and after reinfusion were studied. RESULTS: Throughout the study, weekly single-pool Kt/V, equilibrated Kt/V, and TAC urea remained constant. However, standard Kt/V increased and TAD urea decreased on daily OL-HDF. There were no statistical differences during the time span of 12 months in pH, cations (Na, K), anions (Cl, HCO3(-) AG, and lactate), or SIDa, SIDe, and SIG pre-HDF; while pH and HCO3(-) TAD decreased from 0.02 and 1.02 +/- 0.74 mEq/L, to 0.01 and 0.64 +/- 0.52 mEq/L, respectively (p<0.01). Net albumin charge and AG increased significantly at dialyzer outlet and decreased after reinfusion. CONCLUSIONS: We did not observe changes in the acid-base balance in patients who switched from 3 times a week to short daily OL-HDF. The main benefit observed was a lower pH and bicarbonate TAD. This shows a better physiology for daily OL-HDF.