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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.)

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.)

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: The prevalence of Takotsubo syndrome in hip fracture is not known., Methods: Hip fracture patients were evaluated in a multidisciplinary unit. Patients with ECG abnormalities and increased troponin I values at the time of hospital admission were included in the study Follow-up was clinical at 30 days and by telephonic interview at one year., Results: Between October 1st 2011 to September 30th 2016, 51 of 1506 patients had preoperative evidence of myocardial damage. Eight, all females, fulfilled the Mayo criteria for Takotsubo syndrome, six had no coronary lesions. Hip surgery was uneventful, and all eight were alive at thirty days, and seven of these were still alive after one year. Forty-three patients had myocardial infarction: mortality at thirty days and one year were 11% and 44% (p<0.0001, Student's t-test; log-rank test)., Conclusion: At least 15% of patients with hip fracture and preoperative myocardial damage had Takotsubo syndrome. They were all elderly females. Contrary to myocardial infarction, Takotsubo syndrome has a favourable long term prognosis., Competing Interests: Conflict of interest None to declare., (© 2020 Carlo Rostagno, Gianluca Polidori, Alice Ceccofiglio, Alessandro Cartei, Alberto Boccaccini, Adriano Peris, Gaia Rubbieri, Roberto Civinini, Massimo Innocenti, published by Sciendo.)

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.)

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.)

Aims: To investigate the ability of 30-min electroencephalogram (EEG), short-latency somatosensory evoked potentials (SEPs) and brain computed tomography (CT) to predict poor neurological outcome (persistent vegetative state or death) at 6 months in comatose survivors of cardiac arrest within 24 h from the event., Methods: Prospective multicentre prognostication study in seven hospitals. SEPs were graded according to the presence and amplitude of their cortical responses, EEG patterns were classified according to the American Clinical Neurophysiology Society terminology and brain oedema on brain CT was measured as grey/white matter (GM/WM) density ratio. Sensitivity for poor outcome prediction at 100% specificity was calculated for the three tests individually and in combination. None of the patients underwent withdrawal of life-sustaining treatments before the index event occurred., Results: A total of 346/396 patients were included in the analysis. At 6 months, 223(64%) had poor neurological outcome; of these, 68 were alive in PVS. Bilaterally absent/absent-pathological amplitude cortical SEP patterns, a GM/WM ratio<1.21 on brain CT and isoelectric/burst-suppression EEG patterns predicted poor outcome with 100% specificity and sensitivities of 57.4%, 48.8% and 34.5%, respectively. At least one of these unfavourable patterns was present in 166/223 patients (74.4% sensitivity). Two unfavourable patterns were simultaneously present in 111/223 patients (49.7% sensitivity), and three patterns in 38/223 patients (17% sensitivity)., Conclusions: In comatose resuscitated patients, a multimodal approach based on results of SEPs, EEG and brain CT accurately predicts poor neurological outcome at 6 months within the first 24 h after cardiac arrest., (Copyright © 2019 Elsevier B.V. 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.

Objectives: To evaluate the effects of perioperative myocardial infarction in patients with hip fracture referred to multidisciplinary unit at a tertiary teaching hospital., Methods: 1030 patients with hip fracture underwent troponin measurement, electrocardiogram and echocardiogram at admission, 24 and 48 h after surgery. Exclusion criteria were age < 70 years, severe aortic stenosis, myocardial infarction <30 days, stress cardiomyopathy, renal failure, sepsis, active neoplastic disease. End-points were 30-day and 1 year mortality., Results: Troponin I levels ≥0.5 μg/l were found in 129/1030. 37 of them were excluded according to reported criteria. In the 92 patients included in the study in hospital and 1 year mortality were significantly higher than in controls (12.5% vs 3.5%, p .0012 and respectively 44% vs 16.1% at 12 months, p < .001). 18 patients underwent coronary angiography within 1 week from hip surgery. All had multivessel coronary artery disease. One patient died after angiography. At multivariate logistic analysis age (OR 1.09, 95% CI = 1.01 to 1.19, p = .044) and creatinine values (OR = 7. 55, 95% CI = 1.26 to 45.3, p = .02) were independent predictive factors of 1 year mortality whereas coronary revascularization (OR = 0.15, 95% CI = 0.03 to 0.78, p = .024) was an independent factor associated with improved survival., Conclusions: Perioperative TnI elevation is associated with a significantly increase in 30-day and 1-year mortality. Severe coronary disease may be suspected in patients with perioperative myocardial infarction after hip fracture surgery. Our study is one of the first providing data on the safety and feasibility of early (inhospital) coronary angiograpy and PCI after hip surgery. Further studies are needed to establish indication of coronary angiography in these patients., (Copyright © 2018. Published by Elsevier B.V.)

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: To report the development of the first robot-assisted kidney transplantation (RAKT) programme from deceased donors, examining technical feasibility and early perioperative and functional outcomes at a referral academic centre., Patients and Methods: A RAKT programme was developed in 2016 at our institution following structured modular training. Specific inclusion/exclusion criteria for both living and deceased donors were set. Data from patients undergoing RAKT from January 2017 to April 2018 were prospectively collected in an a priori developed web-based data set. RAKT followed the principles of the Vattikuti Urology Institute-Medanta technique, with specific technical modifications based on clinical recipient characteristics, as well as surgeon's skills and preference during the learning curve. Technical feasibility of RAKT from deceased donors and evaluation of perioperative and early functional outcomes were the main study endpoints., Results: In all, 17 RAKTs were performed during the study period. Of these, six were from living donors and 11 were from deceased donors. All RAKTs were successfully completed without need of conversion. The median (interquartile range [IQR]) console time was 190 (160-220) min and the median (IQR) estimated blood loss was 120 (110-140) mL. The median times to complete venous, arterial and uretero-vesical anastomoses were 21, 22 and 21 min, respectively. The median (IQR) length of stay was 8 (6-12) days. At a median (IQR) follow-up of 8 (6-11) months, five (30%) complications were recorded. Of these, four (24%) were minor (Clavien-Dindo Grade I-II) and one major (Clavien-Dindo Grade IIIb, requiring graft nephrectomy). Overall, two patients were still on dialysis at last follow-up. A significant improvement in graft function was recorded progressively at all postoperative time points., Conclusion: Our preliminary experience outlines that: (i) the development of a RAKT programme is feasible in centres experienced in robotic surgery and open kidney transplantation; (ii) RAKT from deceased donors is feasible from both a technical and logistical perspective; and (iii) RAKT from deceased donors appears to achieve favourable early postoperative and functional outcomes. Larger studies with longer follow-up are needed to confirm these findings and compare the outcomes of RAKT from deceased donors with those from living donors., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

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.)

Background: Five to ten percent of patients with hip fracture have severe aortic valve stenosis (AS). The aim of the present investigation was to evaluate the impact of AS on early and long-term outcome after surgery for hip fracture., Methods: 145 patients with AS and 283 consecutive patients without AS (control group) aged >70 years referred to Azienda Ospadaliera Universitaria (AOU) Careggi for hip fracture were included in the study. The endpoints were incidence of postoperative myocardial infarction, 30-day and 1-year mortality, and a composite endpoint (30-day mortality + myocardial infarction)., Results: 66 patients had mild, 47 moderate and 32 severe AS according to the European Society of Cardiology guidelines. 30-day mortality was 6.2% in AS and 3.1% in controls. Postoperative non-fatal myocardial infarction and composite endpoint were more frequent in AS than in the control group (8.3% vs 1.1%, p<0.001 and 14.5% vs 4.2%, p<0.001, respectively). The risk was significantly higher for patients with severe AS (28.1%). 1-year mortality in patients with moderate/severe AS was 46% in comparison with 16% in mild AS or in the control group (p<0.001). Coronary disease, atrial fibrillation, age, and aortic gradient were independent predictors of mortality in AS., Discussion: AS significantly affects postoperative outcome after surgery for hip fracture. Since not infrequently AS is incidentally diagnosed during hospitalization after trauma, which should be the management in these patients after hip surgery? How many might benefit from surgical valve replacement or transcatheter aortic valve replacement? A heart team evaluation may be suggested before discharge for most of these patients., Level of Evidence: IV., Competing Interests: Competing interests: None declared.

Purpose: The aim of this study was to evaluate the outcomes of an integrated multidisciplinary hip fracture unit through the following parameters: time to surgery, mortality, return to activities of daily living, adherence to re-fractures prevention programs., Methods: Six hundred seventy-seven consecutive patients with hip fracture were included in the study. We calculated the time to surgery as the time in hours from admission until surgery. The in-hospital mortality was calculated as the number of deaths that occurred before discharge. Each patient was then evaluated post-operatively at six weeks, three months, and one year. We studied basic activity of daily living (BADL) and the New Mobility Scale (NMS). Adherence to re-fractures prevention programs was also evaluated., Results: 88.9% of patients underwent surgery within two calendar days from admission. In-hospital mortality was 2.4%, and the overall mortality at one year from the intervention was 18.7%. Full mobility status or a low impairment of the mobility status was reached in 32.1% of the patients at one year and a level ≥ 3 of autonomy in BADL was reached in 62.4% (338/542) of patients. Three hundred forty-two patients were prescribed a specific therapy for secondary prevention of re-fracture., Conclusions: An integrated, multidisciplinary model for the treatment of hip fragility fractures was effective in reducing time to surgery and mortality, increasing the level autonomy and mobility status and promoting adherence to re-fracture therapy.

Background: Bedside diagnostic laparoscopy could be helpful in extremely critically ill patients. The aim of this retrospective study is to evaluate the safety and diagnostic accuracy of bedside diagnostic laparoscopy in the identification of intra-abdominal pathology in critically ill patients and to compare its accuracy and outcomes with the ones of laparotomy., Patients and Methods: A retrospective review was conducted on the medical records of patients admitted to the Intensive Care Unit (ICU) of Careggi University Hospital and submitted to bedside diagnostic laparoscopy between January 2006 and May 2017. This group of patients was compared with a group of patients that were admitted to the ICU and submitted directly to explorative laparotomy for suspected intra-abdominal pathologies., Results: One hundred and twenty-nine patients (M/F = 81/48, mean age = 71.64 years) underwent bedside diagnostic laparoscopy in ICU. 154 patients instead were submitted directly to explorative laparotomy in operatory room (mean age 75.70 years, M/F = 94/60). Among the 129 patients submitted to bedside laparoscopy, 53.49% were positive for intra-abdominal pathologies whereas 46.51% were negative, while among the 154 patients submitted directly to laparotomy, 76.62% were positive for intra-abdominal pathologies whereas 23.38% were negative. In 55.03% of all patients submitted to bedside laparoscopy, a non-therapeutic laparotomy was avoided, while the 33.76% of patients submitted directly to laparotomy had a non-therapeutic laparotomy that could be avoidable., Conclusions: Our results pinpoint the advantages of performing bedside diagnostic laparoscopy in the ICU setting, which can be considered an option every time there is the suspicion of an intra-abdominal pathology., Competing Interests: Authors certify that there is no actual or potential conflict of interest in relation to this article and they state that there are no financial interests or connections, direct or indirect or other situations that might raise the question of bias in the work reported or the conclusions, implications or opinions stated – including pertinent commercial or other sources of funding for the individual author(s) or for the associated department(s) or organisation(s), personal relationships or direct academic competition.

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.)

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: Donation after circulatory death (DCD) is an emerging way to implement organ procurement for transplantation. In Italy, until June 2016, the only formal DCD program was implemented in Pavia, the so-called "Alba program.", Methods: We describe our one-year experience of the DCD program implemented at the Careggi Teaching Hospital (Florence, Italy) since June 2016. We specifically describe organizational changes induced by the DCD program on our pre-existing Donation After Brain Death (DBD) program and DCD activity., Results: Eighteen activations were recorded (i.e. 18 DCD donors), among whom Seven donors were discarded due to opposition in five patients and failure to meet activation criteria in two (inability to contact relatives). Our population comprises 11 donors among whom eight patients were Maastricht type II donors while three were Maastricht type III donors. 22 kidneys and six livers were retrieved, while 13 kidneys and two liver were transplanted., Conclusions: A DCD program was feasible and increased procurement of splancnic organs (kidney and liver). Starting a DCD program in a traditionally oriented to DBD poses some organizational and cultural problems. A skilled, experienced ECMO team is necessary to guarantee organ ex vivo perfusion. Another important aspect for the implementation of a DCD program is the collaboration with the emergency system which allows a therapeutic approach of patients with cardiac arrest.

The use of donation after circulatory death (DCD) has increased significantly to face the persistent mismatch between supply and demand of organs for transplantation. While controlled (c) DCDs have warm ischemic time (WIT) that can be estimated, the WIT is often inexact and extended in uncontrolled DCD (uDCD), making assessment of injury difficult. We aimed at investigating the effects of cold ischemia on potential donor organ damage in the course of nRP by assessing the dynamic variations of transaminases and creatinine values in 17 uDCD donors. In our series, lactate values did not show significant changes during the study period (P = 0.147). Creatinine values did not significantly changed while transaminases progressive increased throughout the study period, even if it was significant only for AST (P = 0.035). According to our data, nRP duration affects splanchnic organs, being the liver sensitive to hypoperfusion, and serial biochemical measurements could help in detecting organ functional status., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Family refusal (FR) to heart beating donation (HBD) in Intensive Care Unit (ICU) is increasing in recent years with a significant impact on the number of transplantable organs. Fostering setting humanization, quality of relationships, respect for will and family reliance towards ICU could be relevant in containing FR to organ donation (OD) in ICU. Our aims were to highlight the effects of structural features of ICUs and humanization determinants on FR in HBD process, and to describe visiting policies, structure and modalities of support in ICUs., Methods: A survey was conducted among all the ICUs of the Tuscany Region included in the National Transplant System of the Ministry of Health in Italy. Data on ICUs' general and architectural characteristics, visiting policies and support for families were collected. Baseline characteristics of brain dead certified patients (BDCPs) were retrieved from the Registry of the Regional Transplant Centre., Results: Twenty-nine (93.5%) ICUs out of 31 completed the survey. 330 BDCPs were managed during 2016 in the ICUs studied, with an opposition rate of 33.3%. The following independent factors for opposition emerged: BDCPs' age (OR=1.025; 95% CI: 1.007-1.042; P=0.005), ICU length of stay (LOS) (OR=1.065; 95% CI: 1.005-1.128; P=0.034) and the availability of an ICU team trained in procurement (OR=0.472; 95% CI: 0.275-0.811; P=0.007)., Conclusions: Older age of BDCPs and a prolonged ICU LOS resulted in FR. ICU team specific education emerged as the only modifiable protective factor for oppositions, thus continuous and in-depth training programs for physicians and nurses could be of importance in preventing FR.

Introduction: Prognosticating outcome after cardiac arrest(CA) requires a multimodal approach. However, evidence regarding combinations of methods is limited. We evaluated whether the combination of electroencephalography(EEG), somatosensory evoked potentials(SEPs) and brain computed tomography(CT) could predict poor outcome., Methods: We screened our database regarding patients successfully resuscitated after CA, for whom EEG, SEPs and brain CT were available within 24 h. EEG patterns were classified according to American Clinical Neurophysiological Society terminology; SEPs were graded accounting for the cortical responses of each hemisphere; and the grey matter/white matter(GM/WM) ratio was evaluated by brain CT. EEG patterns, SEP findings and GM/WM ratio (with a specificity of 100%) were, individually and in combination, related to poor outcome (death/unresponsive wakefulness state) at 6-month follow-up, using the cerebral performance categories(CPC)., Results: EEG, SEPs and brain CT were available in 183/273(67%) patients. Bilateral absent/absent-pathologic(AA/AP) cortical SEPs predicted a poor outcome with a sensitivity of 58.5%. A GM/WM ratio <1.21 predicted a poor outcome with a sensitivity of 50.4%. Isoelectric/burst-suppression EEG patterns predicted a poor outcome with a sensitivity of 43%. If at least one of these poor prognostic patterns was present, sensitivity for an ominous outcome increased to 71.5%. If, in the same subject, two poor prognostic patterns were simultaneously present, sensitivity was 48%. If all three poor prognostic patterns were present, sensitivity decreased by up to 23%., Conclusion: In this population, in which life-sustaining treatments were never suspended, the combination of EEG, SEPs and brain CT improved the sensitivity, maintaining the specificity of poor outcome prediction., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Objective: Many extracorporeal membrane oxygenation (ECMO) centers for respiratory failure and ECMO mobile teams were instituted during the H1N1 pandemic. Data on transportation are scarce and heterogeneous. The authors therefore described the experience of their referral ECMO center for severe respiratory failure from 2009 to 2016 and gave a comprehensive report of transfers performed by their mobile ECMO team., Design: Observational retrospective study., Setting: An intensive care unit (ECMO referral center) in a teaching hospital., Participants: One hundred and sixty consecutive patients with acute respiratory distress syndrome refractory to conventional treatment requiring veno-venous (VV)-ECMO., Intervention: VV-ECMO implantation., Measurements and Main Results: In this series, the transferred patients on ECMO averaged 57%, with annual percentages ranging from 28% to 90% over the years. No adverse event was observed during transportation. A progressive increase in simplified acute physiology score (SAPS) values and in the use of norepinephrine were detectable (p = 0.048 and p = 0.037, respectively) as well as in neuromuscular blockers use (p = 0.004). Dual-lumen cannule were more frequently used in recent years (p < 0.001). The overall mortality rate was 40% (64/160), with no differences over the years or between transferred and local patients. Body mass index and pre-ECMO neuromuscular blockers and SAPS were independent predictors for early mortality (when adjusted for age)., Conclusions: The workload of the authors' referral center and mobile team did not change, documenting that severe respiratory failure requiring VV-ECMO support is still a clinical need. No difference in mortality rate was detectable during this period or between transferred and local patients who were managed by the same team., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In patients with severe cardiac dysfunction refractory to conventional therapies, extracorporeal membrane oxygenation used in veno-arterious modality can provide temporary circulatory assistance (extracorporeal life support, ECLS). Since it is an invasive and complex technique, its use is potentially burdened by severe complications, thus requiring careful nursing and medical care during intensive cardiac care unit stay. The use of ECLS requires specific skills such as knowledge of protective mechanical invasive ventilation, specific echocardiographic evaluation, accurate monitoring of hemodynamics and laboratory tests. A patient on ECLS is at high risk of thrombotic and hemorrhagic complications that could be fatal, hence specific pro- and anti-hemostatic therapy is needed. Moreover, the knowledge of some peculiar aspects of ECLS system and management can help doctors to avoid several complications such as limb ischemia, left ventricular overload and regional perfusion discrepancy. In conclusion, careful management by adequately trained personnel is required.

The data presented in this article are related to our research article entitled 'Neurophysiological and neuroradiological multimodal approach for early poor outcome prediction after cardiac arrest' (Scarpino et al., 2018) [1]. We reported two additional analyses, including results gathered from somatosensory evoked potentials(SEPs), brain computed tomography(CT) and electroencephalography(EEG) performed on 183 subjects within the first 24 h after cardiac arrest(CA). In the first analysis, we considered the Cerebral Performance Categories(CPC) 3, 4 and 5a,b (severe disability, unresponsive wakefulness state, neurological death and non-neurological death, respectively) as poor outcomes. In the second analysis, patients that died from non-neurological causes (CPC 5b) were excluded from the analysis. Concerning the first analysis, bilateral absent/absent-pathologic(AA/AP) cortical SEPs predicted poor outcome with a sensitivity of 49.3%. A Grey Matter/White Matter(GM/WM) ratio <1.21 predicted poor outcome with a sensitivity of 41.7%. Isoelectric/burst-suppression EEG patterns predicted poor outcome with a sensitivity of 33.5%. If at least one of these poor prognostic patterns was present, the sensitivity for an ominous outcome increased to 60.9%. Concerning the second analysis, AA/AP cortical SEPs predicted poor outcome with a sensitivity of 52.5%. GM/WM ratio <1.21 predicted poor outcome with a sensitivity of 50.4%. Isoelectric/burst-suppression EEG patterns predicted poor outcome with a sensitivity of 39.8%.

Transplant renal artery stenosis (TRAS) is the most frequent vascular complication after kidney transplantation (KT) and has been associated with potentially reversible refractory hypertension, graft dysfunction, and reduced patient survival. The aim of the study is to describe the outcomes of a standardized Duplex Ultrasound- (DU-) based screening protocol for early diagnosis of TRAS and for selection of patients potentially requiring endovascular intervention. We retrospectively reviewed our prospectively collected database of KT from January 1998 to select patients diagnosed with TRAS. The follow-up protocol was based on a risk-adapted, dynamic subdivision of eligible KT patients in different risk categories (RC) with different protocol strategies (PS). Of 598 patients included in the study, 52 (9%) patients had hemodynamically significant TRAS and underwent percutaneous angioplasty (PTA) and stent placement. Technical and clinical success rates were 97% and 90%, respectively. 7 cases of restenosis were recorded at follow-up and treated with re-PTA plus stenting. Both DU imaging and clinical parameters improved after stent placement. Prospective high-quality studies are needed to test the efficacy and safety of our protocol in larger series. Accurate trial design and standardized reporting of patient outcomes will be key to address the current clinical needs.

The measurement of mechanical effects associated with the dilatation phase of a percutaneous dilatational tracheostomy is of primary importance to identify the causes of major complications associated with this procedure, such as tracheal cartilage subluxation or fracture and bleeding. Such information can be very useful also for the design of better instruments and procedures. The aim of this study was to present a methodology to evaluate mechanical effects of the dilatation phase of a percutaneous dilatational tracheostomy on the tracheal rings and adjacent anatomical structures. Forces and moments were measured through a dilator instrumented with strain gauges. Two surgeons, with different levels of expertise, performed the percutaneous dilatational tracheostomy on a lifelike reproduction of an adult head, specifically designed for training professionals. The modified dilator was effective in measuring forces involved in the percutaneous dilatational tracheostomy without affecting the ability of the operator to perform the procedure. The main contribution to the insertion of the dilator was given by the axial force, defined as the force acting on the handle, compressing it (mean and peak force: 48.8 and 88.2 N for Surgeon 1, 31.3 and 82.8 N for Surgeon 2, respectively). The proposed method was effective in measuring differences between procedures performed by surgeons with different amounts of experience in terms of duration, forces applied and repeatability. In addition, it may have applications for use as a feedback for incorrect positioning or excessively variable pressure during the training of surgeons for the execution of percutaneous dilatational tracheostomy.

Bilirubin is known as a marker of hepatic dysfunction and is incorporated in scoring algorithms to assess prognosis in critically ill patients. No data are so far available on the prognostic role of hepatic dysfunction in patients with severe ARDS on venovenous extracorporeal membrane oxygenation (VV-ECMO) support. In 112 consecutive patients with severe ARDS treated with VV-ECMO, we aimed at assessing whether increased bilirubin during the first 72 h could affect early death. Increased serum bilirubin (≥1.2 mg/dl) was detectable in 29 patients (25.9%) who were older (p = 0.031), exhibited a higher SOFA score (p = 0.006), were more frequently given pre-ECMO muscular blockers (p = 0.001) and supported with ECMO for a longer period (p = 0.024), when compared to patients with normal bilirubin. No difference in in-ICU mortality rate was observed between the two subgroups. In survivors, bilirubin showed a progressive and significant decrease (p = 0.032) during the first 72 h of ECMO support, while it increased in dead patients (p = 0.007).The mortality rate was higher in patients with increased bilirubin at 24, 48 and 72 h after ECMO start in respect to that of patients with normal values. Pre-ECMO increased bilirubin values (≥1.2 mg/dl), being detectable in about one-fourth of the entire population, is not associated with increased in-ICU mortality, while the persistence of increased bilirubin values after 24 h of ECMO start and within the first 3 days identified a subgroup of patients at higher risk of death.

Transcranial Doppler (TCD) is able to detect cerebral hemodynamic changes in real-time. Impairment of cerebral blood flow during veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) treatment is referred to in the literature. Several cerebrovascular complications can affect VA ECMO patients, eventually leading to brain death (BD). Transcranial Doppler is a worldwide accepted technique for cerebral circulatory arrest (CCA) diagnosis for BD confirmation, and in Italy, it is mandatory in certain clinical conditions. Nowadays, no data have been published on the use of TCD as a confirmation test in VA ECMO patients evolved to BD. The aim of our study was to investigate the feasibility of TCD in CCA diagnosis during VA ECMO treatment. Thirty-two TCD examinations, performed in 25 patients on VA ECMO, were retrospectively analyzed, and factors that could be responsible for TCD waveforms abnormalities were reviewed. Differences in TCD patterns were detected depending on values of left ventricular ejection fraction and the absence or presence of intraaortic balloon pump (IABP). Four categories of different TCD patterns were then identified. In five BD patients, diagnostic CCA patterns in all cerebral arteries were identified by TCD. Our data suggest that cerebral hemodynamic changes due to both residual cardiac function and the effects of IABP can be detected by TCD in VA ECMO patients. In the case of BD, TCD seems to be a reliable instrumental test for CCA diagnosis in patients on VA ECMO when a pulsatile flow is maintained (native or IABP support).

Purpose: In critically ill patient it is observed a severe oxidative stress, not only due to the acute pathology but also for some therapeutic treatments. The aim of the present study was to analyze the variations of non-enzymatic antioxidants in plasma during veno-venous ECMO-treatment in a homogeneous population of critical patients with ARDS., Materials and Methods: We carried out a retrospective study enrolling all patients with ARDS by influence A H1N1 treated with veno-venous ECMO. In all patients included, we have recorded clinical and laboratory parameters considered indicators of oxidative stress during the first week of treatment., Results: With regard to non-enzymatic antioxidants evaluated, we observed that both albumin and uric acid decreased significantly, at all observation times, after ECMO-treatment [(25.88±4.51, 18.05±4.27, 16.32±4.57, 19.07±5.10, p<0.05)(g/l), (5.46±1.43, 2.30±1.15, 2.90±2.09, 2.07±1.03, p<0.05)(mg/dl), respectively]. At the same time the amount of insulin administered daily was increased with statistical significance (p=0.03)., Conclusions: The veno-venous ECMO-treatment causes a significant reduction of some of the major non-enzymatic antioxidants and a possible increase in insulin resistance in patients with ARDS by influence A H1N1., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Lactate has been recognised as a prognostic factor in several critical conditions. Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO) is a well-established therapy in patients with Acute Respiratory Disease Syndrome (ARDS) unresponsive to conventional therapy and echocardiography pre ECMO initiation has been recently reported to help in risk stratifying these patients., Methods: We assessed whether the detection of hyperlactataemia could be associated with the presence of left ventricle (LV) or right ventricle (RV) dysfunction in 121 consecutive patients with refractory ARDS., Results: The mortality rate was 42.9% (52/121). Higher dosages of norepinephrine and dobutamine were administered to non survivors (p=0.023 and p=0.047, respectively) who showed significantly higher levels of lactate (p=0.002). At echocardiography, non survivors showed higher values of systolic pulmonary artery pressure (sPAP) (p=0.05) and a higher incidence of RV dysfunction (as indicated by lower Tricuspid Annular Plane Excursion (TAPSE)) and RV dilatation (p=0.001). At multivariate logistic regression analysis, the following variables were independent predictors of death: body mass index (BMI) (OR: 0.914, 95%CI 0.857-0.975, p=0.006), RV dilatation (OR: 0.239, 95%CI 0.101-0.561, p=0.001) and lactate (OR: 1.292, 95%CI 1.015-1.645, p=0.038). Lactate values were directly correlated with the simplified acute physiology score (SAPS) II (r=0.38, p<0.001), while they showed an indirect correlation with left ventricular ejection fraction (LVEF) (r=-0.24, p=0.009) and TAPSE (r=-0.21, p=0.024)., Conclusions: In refractory ARDS, hyperlactataemia before VVV-ECMO identified a subset of patients at higher risk of death, being an independent predictor of in-Intensive Care Unit (ICU) mortality. Lactate values are mainly related to disease severity (as indicated by SAPS II) and haemodynamic impairment (as inferred by LVEF) and RV failure, as (indicated by TAPSE)., (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.)

Heart transplantation rates are limited by a shortage of donor hearts, and left ventricular dysfunction is an important cause. We hypothesized that an early echocardiographic evaluation in severe brain injury (performed within 12 hours from ICU admission) could allow the detection of potentially reversible left ventricular (LV) abnormalities and thus the initiation of tailored treatment whose effects could be assessed at a second echocardiogram performed when brain death develops. We assessed this hypothesis in 49 patients with severe brain injury who were potential heart donors. A reduction in LV ejection fraction (LVEF) (<55%) was present in five patients (10.2%): diffuse hypokinesia in three patients (6.1%), segmental wall motion abnormalities in two (4.1%). Two patients showed apical ballooning (normal LVEF). The three patients with diffuse hypokinesia showed, at the echocardiogram performed 12 hours later, a complete recovery of wall motion and LVEF. Among patients with apical ballooning, a complete resolution was observed in both patients. Two patients were considered potentially eligible for heart donation, resulting in 20% increase in donor retrieval rate. In serious encephalic lesions, potentially evolving toward brain death, echocardiography performed after ICU admission allowed the identification of LV abnormalities, which could be specifically treated with complete resolution., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Brain death (BD) in coma after cardiac arrest (CA) is difficult to predict. Basal ganglia gray matter/white matter (GM/WM) ratio density and somatosensory evoked potentials (SEPs) may differentiate patients evolving toward BD., Methods: We used SEPs and brain computed tomography (CT) after coma onset, within the first 24hours., Results: Of the 160 patients included in the study, 22 (14%) evolved toward BD. SEP patterns predicted BD (ROC area=0.82, P<0.0001). The combination of SEP patterns, bilaterally absent (AA) and absent on one hemisphere and pathological on the other (AP), predicted BD with a sensitivity of 100% and a specificity of 62.3%, with a positive likelihood ratio of 2.65. The GM/WM ratio predicted BD (ROC area=0.68, P=0.01). A GM/WM ratio <1.07 had a sensitivity of 30.4%, a specificity of 94.9%, and a positive likelihood ratio of 6.27. The combination of SEP and CT findings did not increase the prediction of BD., Conclusion: SEPs and brain CT within 24hours predicted BD after CA. Severe SEP findings (SEP patterns: AA, AP) identified a subset of patients in whom BD could occur. Brain CT (GM/WM ratio in basal ganglia) predicted an early evolution toward BD with high specificity but lower sensitivity., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: Serial lactate measurements over time or lactate clearance has been reported to be clinically reliable for risk stratification in different pathologic conditions ranging from sepsis to trauma, but no data are so far available on the behavior of lactate during venovenous extracorporeal membrane oxygenation (VV-ECMO) support in refractory adult acute respiratory distress syndrome (ARDS)., Methods: We assessed lactate values during VV-ECMO support and the prognostic role of lactate clearance at 6, 24, and 72 hours after ECMO start in 126 consecutive patients with refractory ARDS treated with VV-ECMO., Results: Survivors showed a progressive, significant decrease in lactate values throughout the study period, whereas nonsurvivors exhibited a progressive increase. Lactate values (measured before ECMO initiation, as well as 6 and 24 hours after) were independently associated with intensive care unit (ICU) death. A significantly higher lactate clearance was observed for survivors at 72 hours after ECMO start than for nonsurvivors. At logistic regression analysis, lactate clearance at 72 hours after ECMO start was an independent predictor of ICU death (odds ratio 0.988, 95% confidence interval [CI]: 0.995 to 0.982, p = 0.001) (together with age, body mass index, and Sequential Organ Failure Assessment). At receiver operating characteristic curve analysis, lactate clearance at 72 hours after ECMO start cutoff value of -16% had a sensitivity of 68% and a specificity of 63% (area under the curve = 0.67, 95% CI: 0.57 to 0.77, p = 0.002)., Conclusions: Lactate (measured before ECMO initiation, as well as 6 and 24 hours after) is a prognostic factor in patients with refractory ARDS treated with VV-ECMO, and lactate clearance at 72 hours after ECMO initiation helps in the risk stratification of these patients, being independently associated with death., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)