Kidney Transplants From Donors on Extracorporeal Membrane Oxygenation Prior to Death Are Associated With Better Long-Term Renal Function Compared to Donors After Circulatory Death.

Donation after circulatory death (DCD) allows expansion of the donor pool. We report on 11 years of Italian experience by comparing the outcome of grafts from DCD and extracorporeal membrane oxygenation (ECMO) prior to death donation (EPD), a new donor category. We studied 58 kidney recipients from DCD or EPD and collected donor/recipient clinical characteristics. Primary non function (PNF) and delayed graft function (DGF) rates, dialysis need, hospitalization duration, and patient and graft survival rates were compared. The estimated glomerular filtration rate (eGFR) was measured throughout the follow-up. Better clinical outcomes were achieved with EPD than with DCD despite similar graft and patient survival rates The total warm ischemia time (WIT) was longer in the DCD group than in the EPD group. Pure WIT was the highest in the class II group. The DGF rate was higher in the DCD group than in the EPD group. PNF rate was similar in the groups. Dialysis need was the greatest and hospitalization the longest in the class II DCD group. eGFR was lower in the class II DCD group than in the EPD group. Our results indicate good clinical outcomes of kidney transplants from DCD despite the long "no-touch period" and show that ECMO in the procurement phase improves graft outcome, suggesting EPD as a source for pool expansion.

Prevalence, Characteristics, Risk Factors, and Outcomes of Invasively Ventilated COVID-19 Patients with Acute Kidney Injury and Renal Replacement Therapy.

BACKGROUND: There is no information on acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) among invasively ventilated coronavirus disease 2019 (COVID-19) patients in Western healthcare systems. OBJECTIVE: To study the prevalence, characteristics, risk factors and outcome of AKI and CRRT among invasively ventilated COVID-19 patients. METHODS: Observational study in a tertiary care hospital in Milan, Italy. RESULTS: Among 99 patients, 72 (75.0%) developed AKI and 17 (17.7%) received CRRT. Most of the patients developed stage 1 AKI (33 [45.8%]), while 15 (20.8%) developed stage 2 AKI and 24 (33.4%) a stage 3 AKI. Patients who developed AKI or needed CRRT at latest follow-up were older, and among CRRT treated patients a greater proportion had preexisting CKD. Hospital mortality was 38.9% for AKI and 52.9% for CRRT patients. CONCLUSIONS: Among invasively ventilated COVID-19 patients, AKI is very common and CRRT use is common. Both carry a high risk of in-hospital mortality.

Predictors of Pneumothorax/Pneumomediastinum in Mechanically Ventilated COVID-19 Patients.

OBJECTIVE: To determine the incidence, predictors, and outcome of pneumothorax (PNX)/pneumomediastinum (PMD) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). DESIGN: Observational study. SETTING: Tertiary-care university hospital. PARTICIPANTS: One hundred sixteen consecutive critically ill, invasively ventilated patients with COVID-19 ARDS. INTERVENTIONS: The authors collected demographic, mechanical ventilation, imaging, laboratory, and outcome data. Primary outcome was the incidence of PNX/PMD. Multiple logistic regression analyses were performed to identify predictors of PNX/PMD. MEASUREMENTS AND MAIN RESULTS: PNX/PMD occurred in a total of 28 patients (24.1%), with 22 patients developing PNX (19.0%) and 13 developing PMD (11.2%). Mean time to development of PNX/PMD was 14 ± 11 days from intubation. The authors found no significant difference in mechanical ventilation parameters between patients who developed PNX/PMD and those who did not. Mechanical ventilation parameters were within recommended limits for protective ventilation in both groups. Ninety-five percent of patients with PNX/PMD had the Macklin effect (linear collections of air contiguous to the bronchovascular sheaths) on a baseline computed tomography scan, and tended to have a higher lung involvement at intensive care unit (ICU) admission (Radiographic Assessment of Lung Edema score 32.2 ± 13.4 v 18.7 ± 9.8 in patients without PNX/PMD, p = 0.08). Time from symptom onset to intubation and time from total bilirubin on day two after ICU admission were the only independent predictors of PNX/PMD. Mortality was 60.7% in patients who developed PNX/PMD versus 38.6% in those who did not (p = 0.04). CONCLUSION: PNX/PMD occurs frequently in COVID-19 patients with ARDS requiring mechanical ventilation, and is associated with increased mortality. Development of PNX/PMD seems to occur despite use of protective mechanical ventilation and has a radiologic predictor sign.

Bone resorption in autologous cryopreserved cranioplasty: quantitative evaluation, semiquantitative score and clinical significance.

BACKGROUND: Changes after reimplantation of the autologous bone have been largely described. However, the rate and the extent of resorption in cranial grafts have not been clearly defined. Aim of our study is to evaluate the bone flap resorption (BFR) after cryopreservation. METHODS: We retrospectively reviewed 27 patients, aged 18 years or older, subjected to cranioplasty (CP) adopting autologous cryopreserved flap. The BFR was derived from the percentage of decrease in flap volume (BFR%), comparing the first post-operative computed tomography (CT) and the last one available (performed at least 1 year after surgery). We also proposed a semiquantitative scoring system, based on CT, to define a clinically workable BFR classification. RESULTS: After a mean ± SE follow-up of 32.5 ± 2.4 months, the bone flap volume decreased significantly (p < 0.0001). The mean BFR% was 31.7 ± 3.8% and correlated with CT-score (p < 0.001). Three BFR classes were described: mild (14.8% of cases) consisting in minimal bone remodelling, CT-score ≤ 6, mean BFR% = 3.5 ± 0.7%; moderate (51.9% of cases) corresponding to satisfactory cerebral protection, CT-score < 13, mean BFR% = 25.6 ± 2.2%; severe (33.3% of cases) consisting in loss of cerebral protection, CT-score ≥ 13, mean BFR% = 54.2 ± 3.9%. Females had higher BFR% than males (p = 0.022). BFR classes and new reconstructive surgery were not related (p = 0.58). CONCLUSIONS: BFR was moderate or severe in 85.2% of re-implanted cryopreserved flaps. The proposed CT-score is an easy and reproducible tool to define resorption extent.

Successful donation after cardiac death liver transplants with prolonged warm ischemia time using normothermic regional perfusion.

The role of donation after cardiac death (DCD) in expanding the donor pool is mainly limited by the incidence of primary nonfunction (PNF) and ischemia-related complications. Even greater concern exists toward uncontrolled DCD, which represents the largest potential pool of DCD donors. We recently started the first Italian series of DCD liver transplantation, using normothermic regional perfusion (NRP) in 6 uncontrolled donors and in 1 controlled case to deal with the legally required no-touch period of 20 minutes. We examined our first 7 cases for the incidence of PNF, early graft dysfunction, and biliary complications. Acceptance of the graft was based on the trend of serum transaminase and lactate during NRP, the macroscopic appearance, and the liver biopsy. Hypothermic machine perfusion (HMP) was associated in selected cases to improve cold storage. Most notably, no cases of PNF were observed. Median posttransplant transaminase peak was 1014 IU/L (range, 393-3268 IU/L). Patient and graft survival were both 100% after a mean follow-up of 6.1 months (range, 3-9 months). No cases of ischemic cholangiopathy occurred during the follow-up. Only 1 anastomotic stricture completely resolved with endoscopic stenting. In conclusion, DCD liver transplantation is feasible in Italy despite the protracted no-touch period. The use of NRP and HMP seems to earn good graft function and proves safe in these organs. Liver Transplantation 23 166-173 2017 AASLD.

The allocation of pancreas allografts on donor age and duration of intensive care unit stay: the experience of the North Italy Transplant program.

Starting in 2011, the North Italy Transplant program (NITp) has based on the allocation of pancreas allografts on donor age and duration of intensive care unit (ICU) stay, but not on donor weight or BMI. We analyzed the detailed allocation protocols of all NITp pancreas donors (2011-2012; n = 433). Outcome measures included donor characteristics and pancreas loss reasons during the allocation process. Twenty-three percent of the 433 pancreases offered for allocation were transplanted. Younger age, shorter ICU stay, traumatic brain death, and higher eGFR were predictors of pancreas transplant, either as vascularized organ or as islets. Among pancreas allografts offered to vascularized organ programs, 35% were indeed transplanted, and younger donor age was the only predictor of transplant. The most common reasons for pancreas withdrawal from the allocation process were donor-related factors. Among pancreas offered to islet programs, 48% were processed, but only 14.2% were indeed transplanted, with unsuccessful isolation being the most common reason for pancreas loss. Younger donor age and higher BMI were predictors of islet allograft transplant. The current allocation strategy has allowed an equal distribution of pancreas allografts between programs for either vascularized organ or islet transplant. The high rate of discarded organs remained an unresolved issue.

Organ donation after extracorporeal cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest in a metropolitan cardiac arrest centre in Milan, Italy.

INTRODUCTION: Extracorporeal cardiopulmonary resuscitation (ECPR) may improve survival in refractory out-of-hospital cardiac arrest (OHCA) but also expand the donor pool as these patients often become eligible for organ donation. Our aim is to describe the impact of organ donation in OHCA patients treated with ECPR in a high-volume cardiac arrest centre. METHODS: Rate of organ donation (primary outcome), organs harvested, a composite of patient survival with favourable neurological outcome or donation of ≥1 solid organ (ECPR benefit), and the potential total number of individuals benefiting from ECPR (survivors with favourable neurological outcome and potential recipients of one solid organ) were analysed among all-rhythms refractory OHCA patients treated with ECPR between January 2013-November 2022 at San Raffaele Hospital in Milan, Italy. RESULTS: Among 307 adults with refractory OHCA treated with ECPR (95% witnessed, 66% shockable, low-flow 70 [IQR 58-81] minutes), 256 (83%) died during hospital stay, 33% from brain death. Donation of at least one solid organ occurred in 58 (19%) patients, 53 (17%) after determination of brain death and 5 (1.6%) after determination of circulatory death, contributing a total of 167 solid organs (3.0 [IQR 2.5-4.0] organs/donor). Overall, 196 individuals (29 survivors with favourable neurological outcome and 167 potential recipients of 1 solid organ) possibly benefited from ECPR. ECPR benefit composite outcome was achieved in 87 (28%) patients. Solid organ donation decreased from 19% to 16% in patients with low-flow <60 min and to 11% with low-flow <60 min and initial shockable rhythm. CONCLUSIONS: When ECPR fails in patients with refractory OHCA, organ donation after brain or circulatory death can help a significant number of patients awaiting transplantation, enhancing the overall benefit of ECPR. ECPR selection criteria may affect the number of potential organ donors.

Feasibility, safety and efficacy of COVID-19 severe acute respiratory distress syndrome management without invasive mechanical ventilation.

BACKGROUND: COVID-19 acute respiratory distress syndrome (ARDS) is often managed with mechanical ventilation (MV), requiring sedation and paralysis, with associated risk of complications. There is limited evidence on the use of high flow nasal cannula (HFNC). We hypothesized that management of COVID-19 ARDS without MV is feasible. METHODS: Included were all adult patients diagnosed with COVID-19 ARDS, with PaO2/FiO2 ratio <100 at admission, and whose management was initially performed without MV. We evaluated need for intubation during ICU stay, mortality and hospital/ICU length of stay (LOS). RESULTS: Out of 118 patients, 41 were managed only with HFNC from hospital admission (and at least during first 24 hours in ICU) and had a PaO2/FiO2 ratio <100 (72.9±13.0). Twenty-nine out of 41 patients never required MV: 24 of them survived and were discharged home. Their median ICU LOS was 11 (7-17) days, and their hospital LOS was 29 (18-45) days. We identified PaO2/FiO2 ratio at ICU admission as the only significant predictor for need for MV during ICU stay. We also identified age, length of non-invasive respiratory support before ICU admission, mean value of PaO2/FiO2 ratio during first half and whole ICU stay as predictors of mortality. CONCLUSIONS: It is safe to monitor in ICU and use HFNC in patients affected by COVID-19 ARDS who initially present data suggesting an early need for intubation. The 41 patients admitted with a PaO2/FiO2 ratio <100 and initially treated only with HFNC show a 22% mortality that is in the lower range of what is reported in recent literature.

Percutaneous tracheostomy in COVID-19 patients: a new apneic approach.

BACKGROUND: Percutaneous dilation tracheostomy is an aerosol-generating procedure carrying a documented infectious risk during respiratory virus pandemics. For this reason, during the COVID-19 outbreak, surgical tracheostomy was preferred to the percutaneous one, despite the technique related complications increased risk. METHODS: We describe a new sequence for percutaneous dilation tracheostomy procedure that could be considered safe both for patients and healthcare personnel. A fiberscope was connected to a video unit to allow bronchoscopy. Guidewire positioning was performed as usual. While the established standard procedure continues with the creation of the stoma without any change in mechanical ventilation, we retracted the bronchoscope until immediately after the access valve in the mount tube, allowing normal ventilation. After 3 minutes of ventilation with 100% oxygen, mechanical ventilation was stopped without disconnecting the circuit. During apnea, the stoma was created by dilating the trachea and the tracheostomy cannula was inserted. Ventilation was then resumed. We evaluated the safeness of the procedure by recording any severe desaturation and by performing serological tests to all personnel. RESULTS: Thirty-six patients (38%) of 96 underwent tracheostomy; 22 (23%) percutaneous dilation tracheostomies with the new approach were performed without any desaturation. All personnel (150 operators) were evaluated for serological testing: 9 (6%) had positive serology but none of them had participated in tracheostomy procedures. CONCLUSION: This newly described percutaneous dilation tracheostomy technique was not related to severe desaturation events and we did not observe any positive serological test in health workers who performed the tracheostomies.

Early prognosis after severe traumatic brain injury with minor or absent computed tomography scan lesions.

BACKGROUND: To assess the prognostic value of corpus callosum lesions (CCL) and brain stem lesions (BSL) in diffuse axonal injury (DAI) patients. METHODS: From December 1989 to December 2008, 102 consecutive patients with pure DAI were admitted to our neurosurgical intensive care unit. Age, gender, Acute Physiology and Chronic Health Evaluation score, Glasgow Coma Score (GCS), pupillary light reactivity on admission, brain magnetic resonance imaging (MRI) 24 hours to 72 hours after trauma and sepsis, shock, adult respiratory distress syndrome, renal failure, neurosurgery, high intracranial pressure during the 6 months posttrauma were studied with multiple logistic regression, and Cox's proportional hazards, respectively, considering the Glasgow Outcome Scale and the time to recovery of consciousness as outcome variables. RESULTS: Four variables predicted unfavorable Glasgow Outcome Scale (likelihood ratio p<0.0001; Area Under the Receiver Operator Curve (AUROC)=0.92; Naglekerke's R=0.64; Goodness-of-Fit p=0.8679): age (5-year odds ratio [OR], 1.44; 95% CI, 1.14-1.82; p=0.002), bilateral absence of light reflexes (OR, 11.11; 95% CI, 2.19-57.67; p=0.004), multiplicity of CCL (OR, 29.23; 95% CI, 7.06-121.01; p<0.001), and multiplicity of BSL (OR, 9.43; 95% CI, 2.44-36.42; p=0.001). Four variables affected time to recovery of consciousness: age (hazard ratio, 0.98; 95% CI, 0.97-0.99; p=0.009), bilateral absence of light reflexes (hazard ratio, 0.51; 95% CI, 0.27-0.97; p=0.041), multiplicity of CCL (hazard ratio, 0.40; 95% CI, 0.25-0.66; p<0.001), and total GCS on admission (hazard ratio, 1.45; 95% CI, 1.23-1.71; p<0.001). CONCLUSIONS: In DAI patients, bad outcome is predicted by age, bilateral absence of pupillary light reflexes, multiplicity of CCL, and BSL on MRI. Time to recovery of consciousness is predicted by age, bilateral absence of light reflexes, multiplicity of CCL on MRI, and GCS on admission.

Tracheoesophageal Fistula in a COVID-19 Ventilated Patient: A Challenging Therapeutic Decision.

COVID-19 associated severe respiratory failure frequently requires admission to an intensive care unit, tracheal intubation, and mechanical ventilation. Among the risks of prolonged mechanical ventilation under these conditions, there is the development of tracheoesophageal fistula. We describe a case of a severe COVID-19 associated respiratory failure, who developed a tracheoesophageal fistula. We hypothesized that one of the mechanisms for tracheoesophageal fistula, along with other local and general risk factors, is the local infection due to the location of the virus itself in the tracheobronchial tree. The patient was managed successfully with surgical intervention. This case highlights the increased risk of this potentially life-threatening complication among the COVID-19 patient cohort and suggests a management strategy.

COVID-19 second wave: appropriateness of admissions to the Emergency Department of a main metropolitan hospital in Milan.

BACKGROUND: In Europe, Italy and Lombardy, in autumn 2020, there was a steep increase in reported cases due to the second epidemic wave of SARS-Cov-2 infection. We aimed to evaluate the appropriateness of COVID-19 patients' admissions to the ED of the San Raffaele Hospital. METHODS: We compared data between the inter-wave period (IWP, from 1st to 30th September) and the second wave period (WP, 1st October to 15th November) focusing on the ED presentation, discharge priority colour code and outcomes. RESULTS: Out of 977 admissions with a SARS-Cov-2 positive swab, 6% were in the IWP and 94% in the WP. Red, yellow and white code increased (these latter from 1.8% to 5.4%) as well as self-presented in yellow and white code. Discharges home increased from 1.8% to 5.4%, while hospitalizations decreased from 63% to 51%. DISCUSSION: We found a rise in white codes (among self-presented patients), indicating inappropriateness of admissions. The increase in discharges suggests that several patients did not require hospitalization. CONCLUSIONS: The pandemic brought out the fundamental role of primary care to manage patients with low-intensity needs. The important increase in ED admissions of COVID-19 patients caused a reduction of NO-COVID-19 patients, with possible inadequate treatment.

Fast reshaping of intensive care unit facilities in a large metropolitan hospital in Milan, Italy: facing the COVID-19 pandemic emergency

At the end of 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak spread from China all around the world, causing thousands of deaths. In Italy, the hardest hit region was Lombardy, with the first reported case on 20 February 2020. San Raffaele Scientific Institute ­ a large tertiary hospital and research centre in Milan, Italy ­ was immediately involved in the management of the public health emergency. Since the beginning of the outbreak, the elective surgical activity of the hospital was rapidly reduced and large areas of the hospital were simultaneously reorganised to admit and assist patients with coronavirus disease 2019 (COVID-19). In addition, the hospital became the regional referral hub for cardiovascular emergencies in order to keep ensuring a high level of health care to non-COVID-19 patients in northern Italy. In a few days, a COVID-19 emergency department was created, improving the general ward capacity to a total number of 279 beds dedicated to patients with COVID-19. Moreover, the number of intensive care unit (ICU) beds was increased from 28 to 72 (54 of them dedicated to patients with COVID-19, and 18 to cardiology and cardiac surgery hub emergencies), both converting pre-existing areas and creating new high technology spaces. All the involved health care personnel were rapidly trained to use personal protection equipment and to manage this particular category of patients both in general wards and ICUs. Furthermore, besides clinical activities, continuously important research projects were carried out in order to find new strategies and more effective therapies to better face an unprecedented health emergency in Italy.

Post-traumatic interpeduncular cistern hemorrhage as a marker for brainstem lesions.

We retrospectively reviewed a prospectively collected database of our diffuse axonal injury (DAI) patients to evaluate the accuracy of the evidence of interpeduncular cistern (IPC) blood on computed tomography (CT) scan when diagnosing brainstem lesions (BSL) early after trauma. From December 1989 to December 2008 we prospectively maintained a clinical and radiological database of head injured patients admitted to our neurosurgical intensive care unit (ICU) that met the following criteria: coma (Glasgow Coma Scale [GCS] score < 9) following the traumatic event; neurological derangement not ascribable to hypoxia, hypotension, or long-acting drugs able to alter state of consciousness; absence of lesions accounting for the severity of coma either on the admission CT scan or on subsequent CT scans; and no contraindications to magnetic resonance imaging (MRI; e.g., indwelling metallic implants). Patients with MRI evidence of BSL exhibited a significantly higher incidence of IPC blood on CT scan than patients without such evidence (77.92% versus 20.00%; p < 0.0001). However, these same patients showed a similar incidence of lesions not associated with IPC blood (68.83% versus 56%; p = 0.2459). The evidence of IPC blood on CT scan as an indicator of BSL had a sensitivity of 0.78 (95% CI: 0.70, 0.86), and a specificity of 0.80 (95% CI: 0.72, 0.88), with a 3.90 likelihood ratio for a positive CT scan, and a 0.28 likelihood ratio for a negative CT scan. Our data suggest that the finding of IPC blood on CT scan early after trauma in patients with otherwise unexplained coma is a good marker for possible brainstem lesions.