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Background: The prognostic role of right ventricle dilatation and dysfunction (RVDD) has not been elucidated in patients with coronavirus disease (COVID)-related respiratory failure refractory to standard treatment needing extracorporeal membrane oxygenation (ECMO) support., Aim: To assess whether pre veno-venous (VV) ECMO RVDD were related to in-intensive care unit (ICU) mortality., Methods: We enrolled 61 patients with COVID-related acute respiratory distress syndrome refractory to conventional treatment submitted to VV ECMO and consecutively admitted to our ICU (an ECMO referral center) from 31 th March 2020 to 31 th August 2021. An echocardiographic exam was performed immediately before VV ECMO implantation., Results: Males were prevalent (73.8%) and patients with a body mass index > 30 kg/m 2 were the majority (46/61, 75%). The overall in-ICU mortality rate was 54.1% (33/61). RVDD was detectable in more than half of the population (34/61, 55.7%) and associated with higher simplified organ functional assessment (SOFA) values ( P = 0.029) and a longer mechanical ventilation duration prior to ECMO support ( P = 0.046). Renal replacement therapy was more frequently needed in RVDD patients ( P = 0.002). A higher in-ICU mortality ( P = 0.024) was observed in RVDD patients. No echo variables were independent predictors of in-ICU death., Conclusion: In patients with COVID-related respiratory failure on ECMO support, RVDD (dilatation and dysfunction) is a common finding and identifies a subset of patients characterized by a more severe disease (as indicated by higher SOFA values and need of renal replacement therapy) and by a higher in-ICU mortality. RVDD (also when considered separately) did not result independently associated with in-ICU mortality in these patients., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

We assessed whether right ventricle (RV) alterations and their development may have clinical significance in critically-ill Coronavirus Disease (COVID) patients, as detected by serial echocardiograms during Intensive Care Unit (ICU) course. This observational single center study included 98 consecutive patients with COVID-related acute respiratory distress syndrome (ARDS). Three subgroups were considered: RV Dysfunction (Dys) on admission (10/98, 10%), developed RV Dys (17/98, 17%), and no RV Dys (71/98, 73%). Overall mortality at 3 months was 46.9%. The first subgroup was characterized by the highest need for Extracorporeal Membrane Oxygenation (ECMO) support ( P < .001) and a systemic inflammatory activation (as indicated by increased D-dimer), the second one by the lowest PaO2/FiO2 (P/F). At multivariate regression analysis, age and Sequential Organ Failure Assessment score were independent predictors for mortality. Different RV echo patterns were observed in critically ill patients presenting with COVID-related ARDS during ICU stay. RV Dys on admission was characterized by a high inflammatory activation while patients who developed RV Dys during ICU stay showed lowest P/F. Both these two subgroups identify patients with a severe COVID disease which in a high percentage of cases was unresponsive to standard treatment and required the use of ECMO.

Purposes: To assess the effects of inhaled Nitric Oxide (iNO) on right ventricle dimension and function and systolic pulmonary arterial pressures in severe Acute Respiratory Distress (ARDS) due to Sars-Cov2 (COVID) infection., Materials and Methods: We assessed the effects of iNO on right ventricle dimension and function and systolic pulmonary arterial pressures in 12 consecutive COVID-related ARDS patients by means of serial echocardiographic exams (baseline, 12 and 24 h since iNO start)., Results: Inhaled NO administration did not influence systolic pulmonary arterial pressures nor RV dimension and function. No changes were detectable in ventilatory data with iNO administration. Considering the negligible effect on oxygenation, iNO use was discontinued in all cases., Conclusions: In COVID-related severe ARDS iNO administrated as rescue therapy is not able to ameliorate oxygenation nor pulmonary hypertension, as assessed by serial echocardiograms. This finding may be explained by the diffuse loss of hypoxic pulmonary vasoconstriction with increased perfusion around alveolar consolidations which characterizes COVID-related severe ARDS., Competing Interests: Declaration of Competing Interest No conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Background: Organs from donation after circulatory death (DCD) are increasingly used for liver transplantation, due to the persisting organ shortage and waiting list mortality. However, the use of DCD grafts is still limited by the inferior graft survival rate and the increased risk of primary non-function and biliary complications when compared to brain death donors' grafts., Methods: Abdominal normothermic regional perfusion with extracorporeal membrane oxygenation (ECMO) is an in situ preservation strategy. which may mitigate ischemia-reperfusion injuries. and has been proposed to restore blood perfusion after the determination of death thus optimizing liver function before implantation., Results: In this systematic review, we highlighted the clinical evidence supporting the use of normothermic regional perfusion in DCD liver underlying the pathophysiological mechanisms, and technical, logistic, and regulatory aspects., Conclusions: Despite the lack of properly designed, prospective, randomized trials, the current available data suggest beneficial effects of normothermic regional perfusion on clinical outcomes after liver transplantation., (© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Objectives: Venovenous extracorporeal membrane oxygenation (ECMO) support may be considered in experienced centers for patients with acute respiratory distress syndrome (ARDS) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection refractory to conventional treatment. In ECMO patients, echocardiography has emerged as a clinical tool for implantation and clinical management; but to date, little data are available on COVID-related ARDS patients requiring ECMO. The authors assessed the incidence of right ventricular dilatation and dysfunction (RvDys) in patients with COVID-related ARDS requiring ECMO., Design: Single-center investigation., Setting: Intensive care unit (ICU)., Participants: A total of 35 patients with COVID-related ARDS requiring ECMO, consecutively admitted to the ICU (March 1, 2020, to February 28, 2021)., Interventions: Serial echocardiographic examinations. RvDys was defined as RV end-diastolic area/LV end-diastolic area >0.6 and tricuspid annular plane excursion <15 mm., Measurements and Main Results: The incidence of RvDys was 15/35 (42%). RvDys patients underwent ECMO support after a longer period of mechanical ventilation (p = 0.006) and exhibited a higher mortality rate (p = 0.024) than those without RvDys. In nonsurvivors, RvDys was observed in all patients (n = nine) who died with unfavorable progression of COVID-related ARDS. In survivors, weaned from ECMO, a significant reduction in systolic pulmonary arterial pressures was detectable., Conclusions: According to the authors' data, in COVID-related ARDS requiring ECMO support, RvDys is common, associated with increased ICU mortality. Overall, the data underscored the clinical role of echocardiography in COVID-related ARDS supported by venovenous ECMO, because serial echocardiographic assessments (especially focused on RV changes) are able to reflect pulmonary COVID disease severity., Competing Interests: Conflict of Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Study Objectives: To assess whether echocardiography, systematically performed, could help in risk stratifying patients with acute respiratory distress syndrome (ARDS) due to SARS-CoV2 (COVID) infection for non invasive ventilation (NIV) failure., Design: Observational single center investigation., Setting: Intensive care unit., Interventions: Echocardiography., Outcome Measures: NIV failure., Main Results: Seventy-five patients were included in our study. In respect to patients who did not need mechanical ventilation (NIV success), those in the NIV failure subgroup (31 patients, 41 %) were older, with more comorbidities and showed a higher SOFA score and LOS. Higher values of NTpro BNP, CRP and D-dimer were observed in the NIV failure subgroup who exhibited a higher ICU mortality rate. At echocardiographic examination, the NIV failure subgroup showed higher values of RV/LV ratio, systolic pulmonary arterial pressure (sPAP) and lower values of tricuspid annular plane systolic excursion (TAPSE)/SPAP, and PaO2/FiO2. At logistic regression analysis TAPSE/sPAP resulted an independent predictor of NIV failure. At receiving operating characteristic curve analysis, the TAPSE/SPAP cut-off of 0.575 mm/mm Hg showed a sensitivity of 97 % and a specificity of 48 %., Conclusions: Our results documented a marked uncoupling of right ventricular function from the pulmonary circulation (as indicated by TAPSE/sPAP) in COVID-related ARDS treated with non invasive ventilation and the measurement of this parameter, performed on ICU admission, provides independent prognostic relevance for NIV failure., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: Acute brain injury (ABI) can cause out of hospital cardiac arrest (OHCA). The aim of this study was to compare clinical features, mortality and potential for organ donation in patients with OHCA due to ABI vs other causes., Methods: From January 2017 to December 2018, all adult patients presenting to ED for OHCA were considered for the study. Two physicians established the definitive cause of OHCA, according to clinical, laboratory, diagnostic imaging and autoptic findings. Clinical features in patients with OHCA due to ABI or other causes were compared., Results: 280 patients were included in the analysis. ABI was the third most frequent cause of OHCA (21, 7.5%); ABIs were 8 subarachnoid hemorrhage, 8 intracerebral hemorrhage, 2 ischemic stroke, 2 traumatic spinal cord injury and 1 status epilepticus respectively. Neurological prodromes such as seizure, headache and focal neurological signs were significantly more frequent in patients with OHCA due to ABI (OR 5.34, p = 0.03; OR 12.90, p = 0.02; and OR 66.53, p < 0.01 respectively) while among non-neurological prodromes chest pain and dyspnea were significantly more frequent in patients with OHCA due to other causes (OR 14.5, p < 0.01; and OR 10.4, p = 0.02 respectively). Anisocoria was present in 19% of patients with OHCA due to ABI vs 2.7% due to other causes (OR 8.47, p < 0.01). In 90.5% of patients with ABI and in 53.1% of patients with other causes the first cardiac rhythm was non shockable (OR 8.1; p = 0.05). Multivariate logistic regression analysis revealed that older age, active smoking, post-traumatic OHCA, neurological prodromes, anisocoria at pupillary examination were independently associated with OHCA due to ABI. Patients with ABI showed a higher mortality compared with the other causes group (19 pts., 90.5% versus 167 pts., 64.5%; p = 0.015). Potential organ donors were more frequent among ABI than other causes group (10 pts., 47.6% vs 75 pts., 28.9%) however the difference did not reach the statistical significance (p = 0.07)., Conclusions: ABI is the third cause of OHCA. Neurological prodromes, absence of chest pain and dyspnea before cardiac arrest, anisocoria and initial non-shockable rhythm might suggest a neurological etiology of the cardiac arrest. Patients with OHCA due to ABI has an unfavorable outcome, however, they could be candidate to organ donation., Competing Interests: Declaration of Competing Interest none., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Donor management is the key in the complex donation process, since up to 20% of organs of brain death donors (DBD) are lost due to hemodynamic instability. This challenge is made more difficult due to the lack of strong recommendations on therapies for hemodynamic management in DBDs and more importantly to the epidemiologic changes in these donors who are becoming older and with more comorbidities (marginal donors). In the present manuscript we aimed at summarizing the available evidence on therapeutic strategies for hemodynamic management (focusing on vasoactive drugs) and monitoring (therapeutic goals). Evidence on management in elderly DBDs is also summarized. Donor management continues critical care but with different and specific therapeutic goals since the number of donor goals met is related to the number of organs retrieved and transplanted. Careful monitoring of selected parameters (possibly including serial echocardiography) is the clinical tool able to guarantee the achievement and maintaining of therapeutic goals. Despide worldwide differences, norepinephrine is the vasoactive of choice in most countries but, whenever higher doses (> 0.2 mcg/kg/min) are needed, a second vasoactive drug (vasopressin) is advisable. Hormonal therapy (desmopressin, corticosteroid and thyroid hormone) are suggested in all DBDs independently of hemodynamic instability. In the single patient, therapeutic regimen (imprimis vasoactive drugs) should be chosen also according to the potential organs retrievable ( i.e. heart vs liver and kidneys)., Competing Interests: Conflict-of-interest statement: No conflict of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Lung ultrasound (LU) is a useful tool for monitoring lung involvement in novel coronavirus (COVID) disease, while information on echocardiographic findings in COVID disease is to date scarce and heterogeneous. We hypothesized that lung and cardiac ultrasound examinations, serially and simultaneously performed, could monitor disease severity in COVID-related ARDS., Methods: We enrolled 47 consecutive patients with COVID-related ARDS (1st March-31st May 2020). Lung and cardiac ultrasounds were performed on admission, at discharged and when clinically needed., Results: Most patients were mechanically ventilated (75%) and veno-venous extracorporeal membrane oxygenation was needed in ten patients (21.2%). The in-ICU mortality rate was 27%%. On admission, not survivors showed a higher LUS score (p = 0.006) and a higher incidence of consolidations (p = 0.003), lower values of LVEF (p = 0.027) and a higher RV/LV ratio (0.008). At discharge, a significant reduction in the incidence of subpleural consolidations (p < 0.001) and, thus, in LUS score (p < 0.001) and an increase in patter A findings (p < 0.001) together with reduced systolic pulmonary arterial pressures were detectable. In not survivors at final examination, an increased in LUS score (p < 0.001), and in RV/LV ratio (p < 0.001) associated with a reduction in TAPSE (p = 0.013) were observed. A significant correlation was observed between LUS and systolic pulmonary arterial pressure (p = 0.04). LUS and RV/LV resulted independent predictors of in-ICU death., Conclusions: In COVID-related ARDS, the combined lung and cardiac ultrasound proved to be an useful clinical tool in monitoring disease progression and in identifying parameters (LU score and RV/LV ratio) able to risk stratifying these patients., (© 2021. Società Italiana di Medicina Interna (SIMI).)

Background: Critical illness polyneuropathy and myopathy (CIPNM) is a frequent neurological manifestation in patients with acute respiratory distress syndrome (ARDS) from coronavirus disease 2019 (COVID-19) infection. CIPNM diagnosis is usually limited to clinical evaluation. We compared patients with ARDS from COVID-19 and other aetiologies, in whom a neurophysiological evaluation for the detection of CIPNM was performed. The aim was to determine if there were any differences between these two groups in frequency of CINPM and outcome at discharge from the intensive care unit (ICU)., Materials and Methods: This was a single-centre retrospective study performed on mechanically ventilated patients consecutively admitted (January 2016-June 2020) to the ICU of Careggi Hospital, Florence, Italy, with ARDS of different aetiologies. Neurophysiological evaluation was performed on patients with stable ventilation parameters, but marked widespread hyposthenia (Medical Research Council score <48). Creatine phosphokinase (CPK), lactic dehydrogenase (LDH) and mean morning glycaemic values were collected., Results: From a total of 148 patients, 23 with COVID-19 infection and 21 with ARDS due to other aetiologies, underwent electroneurography/electromyography (ENG/EMG) recording. Incidence of CIPNM was similar in the two groups, 65% (15 of 23) in COVID-19 patients and 71% (15 of 21) in patients affected by ARDS of other aetiologies. At ICU discharge, subjects with CIPNM more frequently required ventilatory support, regardless the aetiology of ARDS., Conclusion: ENG/EMG represents a useful tool in the identification of the neuromuscular causes underlying ventilator wean failure and patient stratification. A high incidence of CIPNM, with a similar percentage, has been observed in ARDS patients of all aetiologies., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aims: Due to heterogeneity on the prognostic role of glucose values and glucose variability in Novel Coronavirus (COVID) disease, we aimed at assessing the prognostic role for Intensive Care Unit (ICU) death of admission hyperglycaemia, peak glycemia and glucose variability in critically ill COVID patients: METHODS: 83 patients consecutively admitted for COVID-related Acute Respiratory Distress Syndrome (ARDS) from from 1st March to 1st October 2020., Results: Non survivors were older, with more comorbidities and a more severe disease. Corticosteroids were used in the majority of patients (54/83, 65%) with no difference between survivors and non survivors. Mean blood glucose values, (during the first 24 and 48 h, respectively), were comparable between the two subgroups, as well as SD 24 and CV 24. During the first 48 h, survivors showed significantly lower values of SD 48 (p < 0.001) and CV 48, respectively (p < 0.001) than non survivors., Conclusions: in consecutive COVID-related ARDS patients admitted to ICU hyperglycemia (>180 mg/dl) is more common in non survivors who also showed a significantly higher glucose variability in the first 48 h since ICU admission. Our findings point to the clinical significance of in-ICU glucose control in severe COVID patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Better preservation and evaluation of kidneys from donors after circulatory death serve to increase the number of kidneys available for transplantation and hypothermic machine perfusion has been shown to decrease ischemia reperfusion injury and delayed graft function. Data on relation between hemodynamic parameters during hypothermic machine perfusion and delayed graft function in kidneys from donors after circulatory death are so far scarce and not univocal. We aimed at assessing whether hemodynamic parameters measured during hypothermic machine perfusion (flow, mean perfusion pressure, and renal resistance) are associated with delayed graft function in 26 kidneys retrieved from uncontrolled donors after circulatory death. In our series, the incidence of delayed graft function was 57.7% (15/26). Recipients who developed delayed graft function had a longer warm ischemic time (p = 0.04). All hemodynamic parameters measured during hypothermic machine perfusion were comparable between recipients with delayed graft function and those without. According to our data, in kidneys from uncontrolled donors after circulatory death, a longer warm ischemic time (that is the overall time of no flow, as the sum of the no-flow and the no-touch period) is associated with delayed graft function. This finding underscores the pivotal role of ischemic injury in terms of absence of flow in affecting graft function. No association was detectable between hemodynamic parameters during hypothermic machine perfusion and the development of delayed graft function in our series.

Objectives: Determining early and reliable prognosis in comatose subjects after cardiac arrest is a central component of post-cardiac arrest care both for developing realistic prognostic expectations for families, and for better determining which resources are mobilized or withheld for individual patients. The aim of the study was to evaluate the prognostic accuracy of EEG and SEP patterns during the very early period (within the first 6 h) after cardiac arrest., Methods: We retrospectively analysed comatose patients after CA, either inside or outside the hospital, in which prognostic evaluation was made during the first 6 h from CA. Prognostic evaluation comprised clinical evaluation (GCS and pupillary light reflex) and neurophysiological (electroencephalography (EEG) and somatosensory evoked potentials (SEP)) studies. Prognosis was evaluated with regards to likelihood of recovery of consciousness and also likelihood of failure to regain consciousness., Results: Forty-one comatose patients after cardiac arrest were included. All patients with continuous and nearly continuous EEG recovered consciousness. Isoelectric EEG was always associated with poor outcome. Burst-suppression, suppression and discontinuous patterns were usually associated with poor outcome although some consciousness recovery was observed. Bilaterally absent SEP responses were always associated with poor outcome. Continuous and nearly continuous EEG patterns were never associated with bilaterally absent SEP., Conclusions: During the very early period following cardiac arrest (first 6 h), EEG and SEP maintain their high predictive value to predict respectively recovery and failure of recovery of consciousness. A very early EEG exam allows identification of patients with very high probability of a good outcome, allowing rapid use of the most appropriate therapeutic procedures., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

In Italy, 20 minutes of a continuous flat line on an electrocardiogram are required for declaration of death. In the setting of donation after circulatory death (DCD), prolonged warm ischemia time prompted the introduction of abdominal normothermic regional perfusion (NRP) followed by postprocurement ex situ machine perfusion (MP). This is a retrospective review of DCD liver transplantations (LTs) performed at 2 centers using sequential NRP and ex situ MP. From January 2018 to April 2019, 34 DCD donors were evaluated. Three (8.8%) were discarded before NRP, and 11 (32.4%) were discarded based on NRP parameters (n = 1, 3.0%), liver macroscopic appearance at procurement and/or biopsy results (n = 9, 26.5%), or severe macroangiopathy at back-table evaluation (n = 1, 3.0%). A total of 20 grafts (58.8%; 11 uncontrolled DCDs, 9 controlled DCDs) were considered eligible for LT, procured and perfused ex situ (9 normothermic and 11 dual hypothermic MPs). In total, 18 (52.9%; 11 uncontrolled) livers were eventually transplanted. Median (interquartile range) no-flow time was 32.5 (30-39) minutes, whereas median functional warm ischemia time was 52.5 (47-74) minutes (controlled DCD), and median low-flow time was 112 minutes (105-129 minutes; uncontrolled DCD). There was no primary nonfunction, while postreperfusion syndrome occurred in 8 (44%) recipients. Early allograft dysfunction happened in 5 (28%) patients, while acute kidney injury occurred in 5 (28%). After a median follow-up of 15.1 (9.5-22.3) months, 1 case of ischemic-type biliary lesions and 1 patient death were reported. DCD LT is feasible even with the 20-minute no-touch rule. Strict NRP and ex situ MP selection criteria are needed to optimize postoperative results., (Copyright © 2020 by the American Association for the Study of Liver Diseases.)

Electronic cigarettes are a popular, easily purchased, alternative source of nicotine that is considered safer than conventional tobacco. However, Intentional or accidental exposure to e-liquid substances, mainly nicotine, can lead to serious, potentially fatal toxicity. Emergency and critical care physicians should keep in mind acute intoxication of this poison with a biphasic toxic syndrome. We highlight its potentially fatal outcome and suggest monitoring the adverse effects of nicotine according to a multimodal protocol integrating somatosensory evoked potentials, electroencephalography and neuroimaging data with anamnestic report and toxicological and laboratory data., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In patients with the novel coronavirus (COVID-19) infection, the echocardiographic assessment of the right ventricle (RV) represents a pivotal element in the understanding of current disease status and in monitoring disease progression. The present manuscript is aimed at specifically describing the echocardiographic assessment of the right ventricle, mainly focusing on the most useful parameters and the time of examination. The RV direct involvement happens quite often due to preferential lung tropism of COVID-19 infection, which is responsible for an interstitial pneumonia characterized also by pulmonary hypoxic vasoconstriction (and thus an RV afterload increase), often evolving in acute respiratory distress syndrome (ARDS). The indirect RV involvement may be due to the systemic inflammatory activation, caused by COVID-19, which may affect the overall cardiovascular system mainly by inducing an increase in troponin values and in the sympathetic tone and altering the volemic status (mainly by affecting renal function). Echocardiographic parameters, specifically focused on RV (dimensions and function) and pulmonary circulation (systolic pulmonary arterial pressures, RV wall thickness), are to be measured in a COVID-19 patient with respiratory failure and ARDS. They have been selected on the basis of their feasibility (that is easy to be measured, even in short time) and usefulness for clinical monitoring. It is advisable to measure the same parameters in the single patient (based also on the availability of valid acoustic windows) which are identified in the first examination and repeated in the following ones, to guarantee a reliable monitoring. Information gained from a clinically-guided echocardiographic assessment holds a clinical utility in the single patients when integrated with biohumoral data (indicating systemic activation), blood gas analysis (reflecting COVID-19-induced lung damage) and data on ongoing therapies (in primis ventilatory settings).

The cardiac involvement in Coronavirus disease (COVID-19) is still under evaluation, especially in severe COVID-19-related Acute Respiratory Distress Syndrome (ARDS). The cardiac involvement was assessed by serial troponin levels and echocardiograms in 28 consecutive patients with COVID-19 ARDS consecutively admitted to our Intensive Care Unit from March 1 to March 31. Twenty-eight COVID-19 patients (aged 61.7 ± 10 years, males 79%). The majority was mechanically ventilated (86%) and 4 patients (14%) required veno-venous extracorporeal membrane oxygenation. As of March 31, the Intensive Care Unit mortality rate was 7%, whereas 7 patients were discharged (25%) with a length of stay of 8.2 ±5 days. At echocardiographic assessment on admission, acute core pulmonale was detected in 2 patients who required extracorporeal membrane oxygenation support. Increased systolic arterial pressure was detected in all patients. Increased Troponin T levels were detectable in 11 patients (39%) on admission. At linear regression analysis, troponin T showed a direct relationship with C-reactive Protein (R square: 0.082, F: 5.95, p = 0.017). In conclusions, in COVID-19-related ARDS, increased in Tn levels was common but not associated with alterations in wall motion kinesis, thus suggesting that troponin T elevation is likely to be multifactorial, mainly linked to disease severely (as inferred by the relation between Tn and C-reactive Protein). The increase in systolic pulmonary arterial pressures observed in all patients may be related to hypoxic vasoconstriction. Further studies are needed to confirm our findings in larger cohorts., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The use of machine perfusion (MP) in liver transplantation (LT) is spreading worldwide. However, its efficacy has not been demonstrated, and its proper clinical use has far to go to be widely implemented. The Società Italiana Trapianti d'Organo (SITO) promoted the development of an evidence-based position paper. A 3-step approach has been adopted to develop this position paper. First, SITO appointed a chair and a cochair who then assembled a working group with specific experience of MP in LT. The Guideline Development Group framed the clinical questions into a patient, intervention, control, and outcome (PICO) format, extracted and analyzed the available literature, ranked the quality of the evidence, and prepared and graded the recommendations. Recommendations were then discussed by all the members of the SITO and were voted on via the Delphi method by an institutional review board. Finally, they were evaluated and scored by a panel of external reviewers. All available literature was analyzed, and its quality was ranked. A total of 18 recommendations regarding the use and the efficacy of ex situ hypothermic and normothermic machine perfusion and sequential normothermic regional perfusion and ex situ MP were prepared and graded according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. A critical and scientific approach is required for the safe implementation of this new technology., (Copyright © 2020 by the American Association for the Study of Liver Diseases.)

Backgrounds: The still high poor outcome of ARDS may be more consequence of circulatory failure than hypoxemia per se. For patients with circulatory failure and ARDS, hemodynamic instability is directly related to ARDS following pulmonary circulation dysfunction and its consequence - right ventricular (RV) dysfunction., Objectives: We hypothesize that in the era of protective ventilation, echocardiographic abnormalities did not parallel ARDS severity, defined by the degree of hypoxemia., Methods: We included 63 consecutively identified mechanically ventilated ARDS patients (1st January 2015 to 31th December 2016). All had echocardiography performed routinely within the first 12 h after ICU admission., Results: The analysis included 110 exams. Twenty-eight patients had severe ARDS (28/63, 44.4%), 27 had moderate ARDS (27/63, 42.1%) and 8 mild ARDS (8/63, 12.7%).There was no difference in echocardiographic findings between mild-moderate and severe ARDS. At Pearson's linear regression analysis, TAPSE was directly correlated with LVEF (r = 0.22, p = 0.021) and inversely with sPAP (r = -0.37, p < 0.001). Systolic pulmonary arterial pressure (sPAP) showed a direct correlation with pCO 2 (r = 0.30, p = 0.002) and an inverse one with pH (r = -0.35, p < 0.001) and TAPSE (r =-0.35, p < 0.001)., Conclusions: Among patients with ARDS, the severity of disease (as indicated by pO2) does not translate into specific cardiac abnormalities, detected by echocardiography. However, RV function (as indicated by TAPSE) is inversely related to pCO 2 and to sPAP (which therefore may be underestimated in presence ofRV dysfunction). Our data strongly suggest that in mechanically ventilated ARDS, the interpretation of echo findings should consider also pCO 2 values., Competing Interests: Declaration of Competing Interest No conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The use of electronic cigarettes (e-cigarettes) is very common worldwide. To date, an increase of nicotine intoxication following an accidental or intentional ingestion/injection of refill solution (e-liquid) has been detected., Case: A 23-year-old man presented with sudden loss of consciousness, bradycardia, and respiratory muscle paralysis after intentional ingestion of e-liquid. Early clinical data, brain computed tomography, and neurophysiological tests (electroencephalogram [EEG] and somatosensory evoked potentials [SEPs]) did not show features with a poor neurological prognostic meaning of an hypoxic encephalopathy. After 4 days, the patient showed bilateral loss of the pupillary reflex, and severe and cytotoxic edema was detected on brain magnetic resonance imaging. SEPs showed a bilateral loss of cortical responses and EEG a suppressed pattern. Nine days after the onset of coma, the patient evolved toward brain death (BD)., Discussion: Because nicotine intoxication might cause respiratory muscle paralysis, without cardiac arrest (CA), it would be important to understand the mechanisms underlying brain damage and to take into account that the current neurological prognostic evidence for hypoxic-ischemic encephalopathy, based on data from patients who all experienced CA may not be reliable. Reporting cases of nicotine intoxication through e-liquid is relevant in order to improve regulatory parameters for e-liquid sale., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

BACKGROUNDCoronavirus disease 19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2. Antiviral immune response is crucial to achieve pathogen clearance; however, in some patients an excessive and aberrant host immune response can lead to an acute respiratory distress syndrome. The comprehension of the mechanisms that regulate pathogen elimination, immunity, and pathology is essential to better characterize disease progression and widen the spectrum of therapeutic options.METHODSWe performed a flow cytometric characterization of immune cell subsets from 30 patients with COVID-19 and correlated these data with clinical outcomes.RESULTSPatients with COVID-19 showed decreased numbers of circulating T, B, and NK cells and exhibited a skewing of CD8+ T cells toward a terminally differentiated/senescent phenotype. In agreement, CD4+ T and CD8+ T, but also NK cells, displayed reduced antiviral cytokine production capability. Moreover, a reduced cytotoxic potential was identified in patients with COVID-19, particularly in those who required intensive care. The latter group of patients also showed increased serum IL-6 levels that inversely correlated to the frequency of granzyme A-expressing NK cells. Off-label treatment with tocilizumab restored the cytotoxic potential of NK cells.CONCLUSIONThe association between IL-6 serum levels and the impairment of cytotoxic activity suggests the possibility that targeting this cytokine may restore antiviral mechanisms.FUNDINGThis study was supported by funds from the Department of Experimental and Clinical Medicine of University of Florence (the ex-60% fund and the "Excellence Departments 2018-2022 Project") derived from Ministero dell'Istruzione, dell'Università e della Ricerca (Italy).

Background: Effectiveness of uncontrolled donation after circulatory death (uDCD) has been recently reported to be 75% according to data coming from some European countries in 2016, but few data are to date available on this topic., Methods: We assessed the utilization rate (as the percentage of donors who were converted into actual donors) in 37 uDCDs consecutively enrolled at our Center (Careggi Teaching Hospital) from June 2016 to June 2019., Results: In three cases, the family did not give consent for donation (3/37, 8.1%). Among the 37 potential uDCDs, 22 became actual donors (22/37, 59%), with 10 livers and 38 kidneys being transplanted, respectively. Fifteen livers were recovered (15/37, 68%), and 10 livers were transplanted (10/15, 67%). Forty-two kidneys were procured and 38 organs transplanted. The overall effectiveness was 78%., Conclusions: According to our 3-year experience, uncontrolled DCDs do represent an additional means of increasing the number of transplanted organs (kidneys and livers) with an acceptable utilization rate. Research on organ viability assessment (for both livers and kidneys from uDCDs) is still in its infancy, and there is probably space for a further wider use of organs from uDCDs., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In the last decades lung ultrasound (LUS) has become of crucial importance in the evaluation and monitoring of a widely range of pulmonary diseases. One of the major benefits which favours this examination, is that this is a non-invasive, low-cost and radiation-free imaging modality which allows repeated imaging. LUS plays an important role in a wide range of pathologies, including cardiogenic oedema, acute respiratory distress syndrome and fibrosis. Specific LUS findings have proved useful and predictive of acute respiratory distress syndrome which is of particular relevance in the suspicion and monitoring of patients with lung disease. Furthermore, several studies have confirmed the role of LUS in the screening of interstitial lung diseases in connective tissue diseases. Given these data, LUS will likely play an important role in the management of COVID-19 patients from identification of specific abnormalities corresponding to definite pneumonia phases and CT scans findings. In addition, LUS could allow reduction in the exposure of health-care workers to potential infection. Herein, we provide a summary on emerging role of lung ultrasound in COVID-19 pneumonia.

Aim: Admission hyperglycemia and glucose variability were associated with mortality in critically ill patients, but data on trauma patients are to date scarce and heterogeneous., Methods: We assessed the prognostic role of ICU death of admission and peak glycemia and glucose variability (indicated by the standard deviation of mean glucose levels and the coefficient of variation of glucose) in 252 patients consecutively admitted for trauma in our ICU (January 1, 2016-December 31, 2018)., Results: The in-ICU mortality rate was 17% (43/252). When compared to patients who died during ICU stay, survivors were younger (p = 0.001), more frequently males (p = 0.002), with a lower incidence of hypertension (p = 0.023). Higher values of SAPS II, SOFA and ISS were observed in nonsurvivors (p < 0.001, p < 0.001, p < 0.001, respectively). Survivors exhibited significantly lower values of admission glycemia (p = 0.001), peak glycemia (p = 0.002) and mean glucose values measured during the first 24 h since ICU admission (p = 0.001). Glucose variability was significantly higher in nonsurvivors, as indicated by higher values of SD and CV (p = 0.001 and p = 0.001, respectively). At multivariate regression analysis, admission glycemia (Model 1), peak glycemia (Model 2) and glucose variability (Model 3 and 4) were independent predictors for in-ICU mortality., Conclusions: Our findings indicate that not only admission glycemia but also peak glycemia and glucose variability show a correlation with in-ICU mortality in trauma patients.

Objectives: Out of hospital cardiac arrest (OHCA) is worldwide quite a common disease, whose mortality still remains high. We aimed at assessing the number of potential donors after OHCA in a tertiary cardiac arrest center with extracorporeal membrane oxygenation (ECPR) and uncontrolled donation after circulatory death (uDCD) programs., Methods: In our single center, prospective, observational study (June 2016 to December 2018), we included all OHCA consecutive patients aged or less 65 years., Results: Our series included 134 OHCA patients. The percentage of patients with return of spontaneous circulation (ROSC) was 36% (48/134). Among patients with no ROSC, ECPR was implanted in 26 patients (26/86, 30%). Among patients without ROSC, 25 patients were eligible for uDCD (25/86, 29%), while 35 patients died at the emergency department. Among patients with ROSC, 15 patients died (15/48, 31%), among whom seven became donors after brain death (7/15, 49%), a percentage which did not vary during the study period. In the subgroup of the 26 patients treated with ECPR, 24 patients died (24/26, 92%) among whom eight were potential donors (33%, 8/34), and only two patients survived (7.7%, 2/26) though with good neurological outcome., Conclusions: The implementation of ECPR and uDCD programs in a tertiary cardiac center is feasible and increased the number of donors, because despite organizational and technical challenges, the uDCD donor pool was 62.5% of all potential donors (25/40).

Objective: In severe acute respiratory distress syndrome (ARDS) treated with extracorporeal membrane oxygenation (ECMO), right ventricular (RV failure) and dilation have been investigated with the use of echocardiography, whereas RV hypertrophy has not been addressed in the literature. The present study assessed the incidence of RV hypertrophy using echocardiography before ECMO treatment and at intensive care unit (ICU) discharge in severe ARDS patients., Design: Observational, retrospective, single-center study., Setting: A single ECMO center., Participants: The study comprised 46 consecutive patients with severe ARDS., Intervention: Echocardiographic evaluation and ECMO support., Measurements and Main Results: A dual-lumen cannula was implanted in most patients (38/46 [82.6%]). Before the start of ECMO, RV hypertrophy was present in 28 patients (60.8%) with no significant differences in baseline characteristics between the 2 subgroups. The ICU mortality rate was 30.4% (14/46), with no difference between patients with RV hypertrophy and those without. At ICU discharge, all patients showed RV hypertrophy., Conclusions: In severe ARDS treated with ECMO support, RV hypertrophy is a common finding and patients with normal RV wall thickness developed RV hypertrophy after ECMO support. The latter finding may suggest that during ECMO support, the right ventricle still may be subjected to increased afterload. However, additional research should be performed to elucidate the spectrum of mechanism(s) involved in the genesis of RV hypertrophy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Although livers from older donors (> 70 y) have been shown to be increasingly more efficiently used for transplant, donor comorbidities are considered additional risk factors. This is quite intriguing as comorbidities are known to increase with advancing age in the donor population., Materials and Methods: We assessed whether age and donor comorbidities influenced liver procurement over a 15-year period in a cohort of 1702 brain-dead donors in Tuscany, Italy., Results: Over the study period, age of potential donors significantly increased (P = .02) as well as the proportion of patients who were > 55 years old. The incidence of hypertension, diabetes mellitus, and previously known coronary artery disease also significantly increased. We observed a progressive increase in the number of transplanted livers from donors with advancing age despite an increase in comorbidities. The highest incidences of traumatic brain injury and anoxic brain injury were observed in the youngest donors. Transaminase levels and use of vasoactive drugs were lower in donors who were ≥ 72 years old., Conclusions: According to our results, criteria for liver donors have already changed. Although age does not seem to be a limiting factor, older donors deserve a more accurate donor selection due to the higher incidence of risk factors (primarily diabetes mellitus).

This review aimed at summarizing the available evidence on liver transplantation from uncontrolled donation after circulatory death (uDCD) on differences in protocols, donor management, in and ex vivo perfusion techniques from center to center. Uncontrolled DCDs represent a unique, complex model of ischemia-reperfusion injury, so far not completely understood. Nevertheless, results on liver transplantation from uDCDs are promising in terms of long-term graft survival. True difficulties still remain since common/shared protocols are not achievable due to legal differences between countries (i.e. no touch period duration). To date, there is no reliable metrics to determine whether a liver is safe to be ex situ perfused or to be transplanted since existing criteria, as stated by investigators themselves, are so far arbitrary. Values and kinetics of transaminanes during normothermic regional perfusion (nRP) should not considered absolute contraindication at least for ex vivo perfusion. Intraoperative evaluation at organ recovery remains pivotal since macroscopic alterations (i.e. hepatic rupture, an abnormal appearance of gall bladder and choledocus) still represent contraindications for organ retrieval. Concerning ex vivo perfusion, the debate is still open, since the choice of type of machine perfusion (mainly hypothermic vs. normothermic) varies from center to center, mainly relying to the single center experience (especially in controlled DCD), surgeons' believes and/or criteria translated from animal models.

Objective: Beyond retrieval and management of patients with severe acute respiratory distress syndrome, an extracorporeal membrane oxygenation (ECMO) center also encompasses several other actions, such as on-call consultations, advice, and counseling, to the physicians at the peripheral centers, but few data are available on this topic. Therefore, the authors describe the composite activities of retrieval and counseling of an ECMO center since 2014., Design: The referral calls addressed to the authors' ECMO center for patients with respiratory failure were prospectively recorded in a dedicated database. Referral call frequency, patient data, and results of the calls were analyzed., Setting: The 12-bed intensive care unit of Careggi Hospital in Florence, the ECMO referral center for Tuscany, and the center of Italy, with a mobile ECMO team., Participants: Patients from intensive care units of peripheral hospitals for whom a referral call was addressed to the authors' ECMO center., Interventions: Many possible responses were given after a referral call, varying from ECMO team deployment to advice or to refusal., Measurements and Main Results: From January 1, 2014, to December 31, 2017, 231 calls were received at the authors' ECMO center, of which 220 calls were for acute respiratory failure cases. Throughout the study period the overall number of calls did not vary, but the percentage of ECMO retrievals decreased, whereas the percentage of ARF patients from peripheral hospital admitted to our ECMO center on conventional ventilation increased. Fifty-five patients were treated by the mobile ECMO team and were transferred on ECMO; 59 were admitted on ventilatory support. In flu periods the overall calls were more frequent than in the no-flu periods (171 v 82 calls), and more ECMO retrieval missions were deployed., Conclusions: During the study period, a decreased number of patients retrieved on ECMO was observed, whereas patients transferred on ventilation increased, with an overall unchanged number of referred patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: To date, there is no agreement on the timing to perform a physical session in patients on veno-venous extracorporeal membrane oxygenation (VV-ECMO). We aimed to assess whether early physiotherapy (within the first week from ECMO start) could affect in-ICU mortality., Methods: Our retrospective observational study included 101 adults supported on VV ECMO from 2009 to 2016, consecutively admitted at our ECMO referral Center in Florence (Italy). Clinical data right before ECMO start were collected for all patients. The level of mobilization using the ICU mobility scale was recorded on the first session and at discharge., Results: Early physiotherapy (within the first week) was more frequently initiated in patients with lower BMI (P=0.013) and it was associated with lower duration of ECMO support (P=0.03), mechanical ventilation (P=0.001) and length of stay (P=0.001). In-ICU mortality was not different between the two subgroups., Conclusions: In patients on VV-ECMO support, physiotherapy is feasible and safe and that early physiotherapy, initiated within the first week from ECMO start, is associated with shorter duration of ECMO support and ICU length of stay.

We provide a step-by-step description of the insertion of a dual-lumen cannula, for venovenous extracorporeal membrane oxygenation support and how a close monitoring by combined transthoracic and transesophageal techniques ensures a safe procedure and can promptly detect complications.

Changes in the causes of brain death may influence the numbers of hearts that can be procured and transplanted. We retrospectively investigated whether the distribution of causes responsible for brain death have changed over a 15-year period in a cohort of 1286 potential heart donor (aged ≤ 60), and whether it influenced heart procurement. Between 2001 and 2016, the age of potential donors significantly increased (p < 0.0001) as well as the relative proportion of postanoxic brain death, while that of traumatic brain injury decreased (p = 0.0007). A significant increase in the use of norepinephrine was detectable. The number of transplanted hearts did not significantly change, with no differences in the age of donors or in the causes of brain death. According to our data, in our 15-year study period, significant changes in the causes of brain death occurred (indicated by a reduction in potential donors following traumatic brain injury) together with an increase in donor age. Nevertheless, the number of transplanted hearts did not change probably thanks to a modified donor management (as inferred by a different use of vasoactive drugs).

Objective: The bilateral absence of cortical Somatosensory Evoked Potentials (SEPs), after cardiac arrest (CA), is a high reliable predictor of poor outcome but it is present in no more than 40% of patients. An amplitude reduction of cortical SEPs was found in about 30% of subjects, but few papers analysed its prognostic significance. The aim of our study is to identify a value of SEP amplitude reduction below which all the CA patients had poor outcome and the relationship between SEP and Electroencephalogram (EEG) patterns., Material and Methods: We analysed comatose patients in whom SEPs and EEG were recorded at 6-12 hours after CA. We evaluated the sensitivity at specificity of 100% of SEP amplitude in predicting the non-recovery of consciousness by plotting Receiver Operating Characteristic (ROC) curves. We also analysed the relationship between SEP amplitude and EEG patterns. Outcome was evaluated at 6 months by Glasgow Outcome Scale., Results: We analysed 119 subjects. According to the ROC analysis (area under the curve = 0.95/CI 0.91-0.99), all patients with a cortical SEP amplitude <0.65 μV did not recover consciousness (GOS 1-2), with a sensitivity of 71.8%. Severe EEG abnormalities (suppression and burst-suppression patterns) were also observed in all these patients., Conclusion: Not only the absence but also a bilateral amplitude reduction of cortical SEPs (<0.65 μV) is associated with ominous prognosis (death or non-recovery of consciousness) with a very high predictive value. However, we emphasize that great caution should be applied before adopting amplitude reduction as a criterion for the poor prognosis of CA patients., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Speckle tracking echocardiography is a novel echocardiographic technique to assess RV myocardial function but no data are so far available in patients with acute respiratory distress syndrome (ARDS), and we aimed at assessing the feasibility of 2 dimensional (2D) speckle tracking echocardiography and the prognostic role of RV free wall speckle tracking strain in 30 consecutive patients with moderate-severe ARDS MATERIALS AND METHODS: In an observational prospective study, 30 consecutive patients with moderate-severe ARDS were enrolled. Echocardiography was performed within 12 hours from ICU admission., Results: Mortality rate was 33% (10/30). Non-survivors showed lower values of pH (7.32 ± 0.09, P = 0.03) and higher troponin I levels (0.32 (0.08-0.46), P = 0.04), NT-pro BNP (3091 (2662-7128), P = 0.009), and SAPS II (60.3 ± 9.6, P < 0.001). At echocardiographic examination, non-survivors showed lower values of TAPSE (18.3 ± 3, P = 0.034) and higher systolic pulmonary arterial pressure (49.6 ± 16, P = 0.05). Two patients (6.6%) did not show valid acoustic windows. Only three patients showed normal values of RV strain free wall (22%, 25%, and 28% absolute values, respectively), among whom one patient died. When compared to survivors, non-survivors showed significantly lower values of RV strain free wall (-10.4 ± 0.10, P < 0.001)., Conclusions: In mechanically ventilated moderate-severe ARDS, 2D speckle tracking is feasible even though difficult acoustic windows are common. Further studies are needed to confirm our findings in a larger cohort of patients., (© 2018 Wiley Periodicals, Inc.)

Background: Acute respiratory distress syndrome (ARDS) has been shown to be frequently associated with haemodynamic instability requiring the use of vasopressors. To date, there is still some uncertainty in the use of veno-venous Extracorporeal Membrane Oxygenation (VV-ECMO) in haemodynamically unstable ARDS patients., Methods: We therefore assessed whether patients receiving pre ECMO vasopressors had a worse prognosis and, furthermore, we reviewed the factors associated with the use of pre ECMO vasopressors in 92 consecutive patients with refractory ARDS treated with VV-ECMO. All patients were submitted to an echocardiogram before implantation., Results: In our series, 55 patients (59.7%) were given a vasopressor. Septic shock is the main cause of vasopressor requirement (45.5%). When compared with patients without vasopressors, the subgroup under vasopressors showed a significantly higher sequential organ failure assessment (SOFA) score (p=0.040), a lower pH (p=0.013), lower pO2 values (p=0.030) and higher lactate levels (p=0.024). A higher incidence of right ventricular (RV) dysfunction and of biventricular dysfunction were observed in patients under vasopressors (p=0.018 and p=0.036, respectively). The intensive care unit (ICU) mortality rate was 43.4% (40/92) with no difference between the two subgroups., Conclusions: In refractory ARDS requiring VV-ECMO, infusion of vasopressors is needed in a high proportion of patients, who did not exhibit a worse prognosis when compared to haemodynamically stable patients. Pre ECMO echocardiography helps in characterising these patients since they showed a higher incidence of RV (and biventricular) dysfunction. According to our data, in ARDS patients refractory to conventional treatment, haemodynamic instability should not be considered a contraindication to VV-ECMO support., (Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)