SARS-CoV-2 and COVID-19: From the Bench to the Bedside.

First isolated in China in early 2020, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the novel coronavirus responsible for the ongoing pandemic of Coronavirus Disease 2019 (COVID-19). The disease has been spreading rapidly across the globe, with the largest burden falling on China, Europe, and the United States. COVID-19 is a new clinical syndrome, characterized by respiratory symptoms with varying degrees of severity, from mild upper respiratory illness to severe interstitial pneumonia and acute respiratory distress syndrome, aggravated by thrombosis in the pulmonary microcirculation. Three main phases of disease progression have been proposed for COVID-19: an early infection phase, a pulmonary phase, and a hyperinflammation phase. Although current understanding of COVID-19 treatment is mainly derived from small uncontrolled trials that are affected by a number of biases, strong background noise, and a litany of confounding factors, emerging awareness suggests that drugs currently used to treat COVID-19 (antiviral drugs, antimalarial drugs, immunomodulators, anticoagulants, and antibodies) should be evaluated in relation to the pathophysiology of disease progression. Drawing upon the dramatic experiences taking place in Italy and around the world, here we review the changes in the evolution of the disease and focus on current treatment uncertainties and promising new therapies.

First-in-human liver transplantation from a centenarian deceased donor after brain death.

Liver transplantation from elderly donors is expanding due to demand for liver grafts, aging of recipients and donors, and introduction of machine perfusion. We report on a liver transplant from a 100-year-old deceased donor after brain death. The liver was transplanted after the use of hypothermic machine perfusion to a 60-year-old recipient with advanced hepatocellular carcinoma undergoing neoadjuvant immunotherapy. Nine months after the transplant, the patient is alive with a functioning graft and no evidence of acute rejection or tumor recurrence.

Tuscany Normothermic Regional Perfusion Mobile Teams for Controlled Donation After Circulatory Death.

INTRODUCTION: To facilitate the implementation of controlled donation after circulatory death (cDCD) programs even in hospitals not equipped with a local extracorporeal membrane oxygenation (ECMO) team, some countries have launched a local cDCD network with an ECMO mobile team for normothermic regional perfusion (NRP). In the Tuscany region, in 2021, the Regional Transplant Authority launched a cDCD program to make the cDCD pathway feasible even in peripheral hospitals with NRP mobile teams, which were "converted" existing ECMO mobile teams, composed of highly skilled and experienced personnel. METHODS: We describe the Tuscany cDCD program, (2021-2023), for cDCD from peripheral hospitals with NRP mobile teams. RESULTS: Twenty-six cDCDs (26/40, 65%) came from peripheral hospitals. Following the launch of the cDCD program, cDCDs from peripheral hospitals increased, from 33% (2021) to 75% (2022 and 2023) of the overall cDCDs. The mean age was 63 years, with older donors (>75 years) in half the cases. The median warm ischemia time was 45 min (20 min are required by the Italian law for death certification), ranging from 35 to 59 min. Among the 20 livers retrieved and 18 kidneys retrieved, 16 livers, and 11 kidneys (single kidney transplantation) were transplanted, after ex vivo reperfusion, respectively. CONCLUSIONS: The use of NRP mobile teams proved to be feasible and safe in the management of cDCD in peripheral hospitals. No complications were reported with NRP despite the advanced age of most cDCDs.

An extensive evaluation of hepatic markers of damage and regeneration in controlled and uncontrolled donation after circulatory death.

Livers from donations after circulatory death (DCDs) are very sensitive to ischemia/reperfusion injury and thus need careful reconditioning, such as normothermic regional perfusion (NRP). So far, its impact on DCDs has not been thoroughly investigated. This pilot cohort study aimed to explore the NRP impact on liver function by evaluating dynamic changes of circulating markers and hepatic gene expression in 9 uncontrolled DCDs (uDCDs) and 10 controlled DCDs. At NRP start, controlled DCDs had lower plasma levels of inflammatory and liver damage markers, including α-glutathione s-transferase, sorbitol-dehydrogenase, malate dehydrogenase 1, liver-type arginase-1, and keratin-18, but higher levels of osteopontin, sFas, flavin mononucleotide, and succinate than uDCDs. During 4-hour NRP, some damage and inflammatory markers increased in both groups, while IL-6, HGF, and osteopontin increased only in uDCDs. At the NRP end, the tissue expression of early transcriptional regulators, apoptosis, and autophagy mediators was higher in uDCDs than in controlled DCDs. In conclusion, despite initial differences in liver damage biomarkers, the uDCD group was characterized by a major gene expression of regenerative and repair factors after the NRP procedure. Correlative analysis among circulating/tissue biomarkers and the tissue congestion/necrosis degree revealed new potential candidate biomarkers.

Metabolomic/lipidomic profiling of COVID-19 and individual response to tocilizumab.

The current pandemic emergence of novel coronavirus disease (COVID-19) poses a relevant threat to global health. SARS-CoV-2 infection is characterized by a wide range of clinical manifestations, ranging from absence of symptoms to severe forms that need intensive care treatment. Here, plasma-EDTA samples of 30 patients compared with age- and sex-matched controls were analyzed via untargeted nuclear magnetic resonance (NMR)-based metabolomics and lipidomics. With the same approach, the effect of tocilizumab administration was evaluated in a subset of patients. Despite the heterogeneity of the clinical symptoms, COVID-19 patients are characterized by common plasma metabolomic and lipidomic signatures (91.7% and 87.5% accuracy, respectively, when compared to controls). Tocilizumab treatment resulted in at least partial reversion of the metabolic alterations due to SARS-CoV-2 infection. In conclusion, NMR-based metabolomic and lipidomic profiling provides novel insights into the pathophysiological mechanism of human response to SARS-CoV-2 infection and to monitor treatment outcomes.

The role of sequential normothermic regional perfusion and end-ischemic normothermic machine perfusion in liver transplantation from very extended uncontrolled donation after cardiocirculatory death.

The use of pre-procurement normothermic regional perfusion (NRP) allowed us to implement controlled DCD liver transplantation with results comparable to brain death donors, but the use of uncontrolled DCD is declining due to logistic challenges and the high incidence of post-transplant complications. In Italy, the mandatory stand-off period of 20 min for DCD donors has driven the combined use of NRP and ex-situ machine perfusion with the intent to counterbalance the negative impact of prolonged warm ischemia. Organ viability during NRP is based on duration of warm ischemia, regional perfusion flow, lactate, transaminases values and histology, and those used in Italy are the widest worldwide. However, this evaluation can be difficult, especially when the acute damage is particularly severe. The use of ex-situ NRP could provide a safe organ evaluation. In the period from 06/2020 to 06/2022, all DCD grafts exceeding NRP viability criteria at a single center were eventually evaluated using ex-situ normothermic machine perfusion. Machine perfusion viability criteria were based on lactate clearance, irrespectively to bile production, unless 1-h transaminases perfusate level were not exceeding 5000 IU/L. Three cases of uncontrolled DCD grafts in excess of NRP viability criteria underwent ex-situ graft evaluation. Two matched ex-situ normothermic machine perfusion viability criteria and were successfully transplanted. Both recipients are doing well after 26 and 5 months after surgery with no signs of ischemic cholangiopathy. This experience suggests that the sequential use of NRP and normothermic machine perfusion may further expand the boundaries of organ viability in uncontrolled DCD liver transplantation.

Echocardiography Before Extracorporeal Membrane Oxygenation in Refractory Respiratory Failure: SARS-CoV-2 Infection Versus Other Etiologies.

OBJECTIVES: The study authors hypothesized that in patients with SARS-CoV-2, COVID-19-related refractory respiratory failure requiring extracorporeal membrane oxygenation (ECMO) support echocardiographic findings (just before ECMO implantation) would be different from those observed in patients with refractory respiratory failure from different etiologies. DESIGN: A single-center observational study. SETTING: At an intensive care unit (ICU). PARTICIPANTS: A total of 61 consecutive patients with refractory COVID-19-related respiratory failure (COVID-19 series) and 74 patients with refractory acute respiratory disease syndrome from other etiologies (no COVID-19 series), all needing ECMO support. INTERVENTIONS: Echocardiogram pre-ECMO. MEASUREMENTS AND MAIN RESULTS: Right ventricle dilatation and dysfunction were defined in the presence of the RV end-diastolic area and/or left ventricle end-diastolic area (LVEDA >0.6 and tricuspid annular plane systolic excursion [TAPSE] <15 mm. Patients in the COVID-19 series showed a higher body mass index (p < 0.001) and a lower Sequential Organ Failure Assessment score (p = 0.002). In-ICU mortality rates were comparable between the 2 subgroups. Echocardiograms performed in all patients before ECMO implantation revealed an incidence of RV dilatation that was higher in patients in the COVID-19 series (p < 0.001), and they also showed higher values of systolic pulmonary artery pressure (sPAP) (p < 0.001) and lower TAPSE and/or sPAP (p < 0.001). The multivariate logistic regression analysis showed that COVID-19-related respiratory failure was not associated with early mortality. The presence of RV dilatation and the uncoupling of RV function and pulmonary circulation were associated independently with COVID-19 respiratory failure. CONCLUSIONS: The presence of RV dilatation and an altered coupling between RVe function and pulmonary vasculature (as indicated by TAPSE and/or sPAP) are associated strictly with COVID-19-related refractory respiratory failure needing ECMO support.

Regional Cerebral Oxygen Saturation to Predict Favorable Outcome in Extracorporeal Cardiopulmonary Resuscitation: A Systematic Review and Meta-Analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to investigate the role of regional cerebral oxygen saturation (rSO2) in predicting survival and neurologic outcomes after extracorporeal cardiopulmonary resuscitation (ECPR). DESIGN: The study authors performed a systematic review and meta-analysis of all available literature. SETTING: The authors searched relevant databases (Pubmed, Medline, Embase) for studies measuring precannulation rSO2 in patients undergoing ECPR and reporting mortality and/or neurologic outcomes. PARTICIPANTS: The authors included both in-hospital and out-of-hospital cardiac arrest patients receiving ECPR. They identified 3 observational studies, including 245 adult patients. INTERVENTIONS: The authors compared patients with a low precannulation rSO2 (≤15% or 16%) versus patients with a high (>15% or 16%) precannulation rSO2. In addition, the authors carried out subgroup analyses on out-of-hospital cardiac arrest (OHCA) patients. MEASUREMENTS AND MAIN RESULTS: A high precannulation rSO2 was associated with an overall reduced risk of mortality in ECPR recipients (98 out of 151 patients [64.9%] in the high rSO2 group, v 87 out of 94 patients [92.5%] in the low rSO2 group, risk differences [RD] -0.30; 95% CI -0.47 to -0.14), and in OHCA (78 out of 121 patients [64.5%] v 82 out of 89 patients [92.1%], RD 0.30; 95% CI -0.48 to -0.12). A high precannulation rSO2 also was associated with a significantly better neurologic outcome in the overall population (42 out of 151 patients [27.8%] v 2 out of 94 patients [2.12%], RD 0.22; 95% CI 0.13-0.31), and in OHCA patients (33 out of 121 patients [27.3%] v 2 out of 89 patients [2.25%] RD 0.21; 95% CI 0.11-0.30). CONCLUSIONS: A low rSO2 before starting ECPR could be a predictor of mortality and survival with poor neurologic outcomes.

Cerium oxide nanoparticles administration during machine perfusion of discarded human livers: A pilot study.

The combined approach of ex situ normothermic machine perfusion (NMP) and nanotechnology represents a strategy to mitigate ischemia/reperfusion injury in liver transplantation (LT). We evaluated the uptake, distribution, and efficacy of antioxidant cerium oxide nanoparticles (nanoceria) during normothermic perfusion of discarded human livers. A total of 9 discarded human liver grafts were randomized in 2 groups and underwent 4 h of NMP: 5 grafts were treated with nanoceria conjugated with albumin (Alb-NC; 50 µg/ml) and compared with 4 untreated grafts. The intracellular uptake of nanoceria was analyzed by electron microscopy (EM) and inductively coupled plasma-mass spectrometry (ICP-MS). The antioxidant activity of Alb-NC was assayed in liver biopsies by glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) assay, telomere length, and 4977-bp common mitochondrial DNA deletion (mtDNA4977 deletion). The cytokine profile was evaluated in perfusate samples. EM and ICP-MS confirmed Alb-NC internalization, rescue of mitochondrial phenotype, decrease of lipid droplet peroxidation, and lipofuscin granules in the treated grafts. Alb-NC exerted an antioxidant activity by increasing GSH levels (percentage change: +94% ± 25%; p = 0.01), SOD (+17% ± 4%; p = 0.02), and CAT activity (51% ± 23%; p = 0.03), reducing the occurrence of mtDNA4977 deletion (-67.2% ± 11%; p = 0.03), but did not affect cytokine release. Alb-NC during ex situ perfusion decreased oxidative stress, upregulating graft antioxidant defense. They could be a tool to improve quality grafts during NMP and represent an antioxidant strategy aimed at protecting the graft against reperfusion injury during LT.

Normothermic regional perfusion in liver transplantation from donation after cardiocirculatory death: Technical, biochemical, and regulatory aspects and review of literature.

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.

Comparison of out of hospital cardiac arrest due to acute brain injury vs other causes.

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.

Persistent Right Ventricle Dilatation in SARS-CoV-2-Related Acute Respiratory Distress Syndrome on Extracorporeal Membrane Oxygenation Support.

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.

Perinatal outcomes of pregnant women with severe COVID-19 requiring extracorporeal membrane oxygenation (ECMO): a case series and literature review.

PURPOSE: Pregnant women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have a higher risk of hospitalization, admission to intensive care unit (ICU) and invasive ventilation, and of acute respiratory distress syndrome (ARDS). In case of ARDS and critical severe coronavirus disease 2019 (COVID-19), the use of extracorporeal membrane oxygenation (ECMO) is recommended when other respiratory support strategies (oxygen insufflation, non-invasive ventilation [NIV], invasive ventilation through an endotracheal tube) are insufficient. However, available data on ECMO in pregnant and postpartum women with critical COVID-19 are very limited. METHODS: A case series of three critically ill pregnant women who required ECMO support for COVID-19 in pregnancy and/or in the postpartum period. RESULTS: The first patient tested positive for COVID-19 during the second trimester, she developed ARDS and required ECMO for 38 days. She was discharged in good general conditions and a cesarean-section [CS] at term was performed for obstetric indication. The second patient developed COVID-19-related ARDS at 28 weeks of gestation. During ECMO, she experienced a precipitous vaginal delivery at 31 weeks and 6 days of gestation. She was discharged 1 month later in good general conditions. The third patient, an obese 43-year-old woman, tested positive at 38 weeks and 2 days of gestation. Because of the worsening of clinical condition, a CS was performed, and she underwent ECMO. 143 days after the CS, she died because of sepsis and multiple organ failure (MOF). Thrombosis, hemorrhage and infections were the main complications among our patients. Neonatal outcomes have been positive. CONCLUSION: ECMO should be considered a life-saving therapy for pregnant women with severe COVID-19.

Sequential Use of Normothermic Regional and Ex Situ Machine Perfusion in Donation After Circulatory Death Liver Transplant.

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.

Epidemiological analysis of a COVID-19 outbreak associated with an infected surgeon.

Control of the novel COronaVIrus Disease-2019 (COVID-19) in a hospital setting is a priority. A COVID-19-infected surgeon performed surgical activities before being tested. An exposure risk classification was applied to the identified exposed subjects and high- and medium-risk contacts underwent active symptom monitoring for 14 days at home. All healthcare professionals (HCPs) were tested for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) at the end of the quarantine and serological tests were performed. Three household contacts and 20 HCPs were identified as high- or medium-risk contacts and underwent a 14-day quarantine. Fourteen HCPs and 19 patients were instead classified as low risk. All the contacts remained asymptomatic and all HCPs tested negative for SARS-CoV-2. About 25-28 days after their last exposure, HCPs underwent serological testing and two of them had positive IgM but negative confirmatory swabs. In a low COVID-19 burden area, the in-hospital transmission of SARS-CoV-2 from an infectious doctor did not occur and, despite multiple and frequent contacts, a hospital outbreak was avoided. This may be linked to the adoption of specific recommendations and to the use of standard personal protective equipment by HCPs.

Electrodiagnostic findings in patients with non-COVID-19- and COVID-19-related acute respiratory distress syndrome.

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.

Delayed graft function and perfusion parameters of kidneys from uncontrolled donors after circulatory death.

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.

Quantitative and qualitative alterations of circulating myeloid cells and plasmacytoid DC in SARS-CoV-2 infection.

SARS-CoV-2 is responsible for a new infectious disease (COVID-19) in which individuals can either remain asymptomatic or progress from mild to severe clinical conditions including acute respiratory distress syndrome and multiple organ failure. The immune mechanisms that potentially orchestrate the pathology in SARS-CoV-2 infection are complex and only partially understood. There is still paucity of data on the features of myeloid cells involved in this viral infection. For this reason, we investigated the different activation status profiles and the subset distribution of myeloid cells and their correlation with disease progression in 40 COVID-19 patients at different stages of disease. COVID-19 patients showed a decrease in the absolute number of plasmacytoid and myeloid dendritic cells, different subset distribution of monocytes and different activation patterns of both monocytes and neutrophils, coupled to a significant reduction of HLA-DR monocyte levels. We found that some of these alterations are typical of all COVID-19 patients, while some others vary at different stages of the disease and correlate with biochemical parameters of inflammation. Collectively, these data suggest that not only the lymphoid, but also the myeloid compartment, is severely affected by SARS-CoV-2 infection.

Utilization rate of uncontrolled donors after circulatory death-a 3-year single-center investigation.

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.

Right Ventricular Hypertrophy in Refractory Acute Respiratory Distress Syndrome Treated With Venovenous Extracorporeal Membrane Oxygenation Support.

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.