Daniele Dondossola

Mechanical Power and Development of Ventilator-induced Lung Injury.

Background:The ventilator works mechanically on the lung parenchyma. The authors set out to obtain the proof of concept that ventilator-induced lung injury (VILI) depends on the mechanical power applied to the lung. Methods:Mechanical power was defined as the function of transpulmonary pressure, tidal volume (TV), and respiratory rate. Three piglets were ventilated with a mechanical power known to be lethal (TV, 38 ml/kg; plateau pressure, 27 cm H2O; and respiratory rate, 15 breaths/min). Other groups (three piglets each) were ventilated with the same TV per kilogram and transpulmonary pressure but at the respiratory rates of 12, 9, 6, and 3 breaths/min. The authors identified a mechanical power threshold for VILI and did nine additional experiments at the respiratory rate of 35 breaths/min and mechanical power below (TV 11 ml/kg) and above (TV 22 ml/kg) the threshold. Results:In the 15 experiments to detect the threshold for VILI, up to a mechanical power of approximately 12 J/min (respiratory rate, 9 breaths/min), the computed tomography scans showed mostly isolated densities, whereas at the mechanical power above approximately 12 J/min, all piglets developed whole-lung edema. In the nine confirmatory experiments, the five piglets ventilated above the power threshold developed VILI, but the four piglets ventilated below did not. By grouping all 24 piglets, the authors found a significant relationship between the mechanical power applied to the lung and the increase in lung weight (r2 = 0.41, P = 0.001) and lung elastance (r2 = 0.33, P < 0.01) and decrease in PaO2/FIO2 (r2 = 0.40, P < 0.001) at the end of the study. Conclusion:In piglets, VILI develops if a mechanical power threshold is exceeded.

Lung inhomogeneities and time course of ventilator-induced mechanical injuries.

Background:During mechanical ventilation, stress and strain may be locally multiplied in an inhomogeneous lung. The authors investigated whether, in healthy lungs, during high pressure/volume ventilation, injury begins at the interface of naturally inhomogeneous structures as visceral pleura, bronchi, vessels, and alveoli. The authors wished also to characterize the nature of the lesions (collapse vs. consolidation). Methods:Twelve piglets were ventilated with strain greater than 2.5 (tidal volume/end-expiratory lung volume) until whole lung edema developed. At least every 3 h, the authors acquired end-expiratory/end-inspiratory computed tomography scans to identify the site and the number of new lesions. Lung inhomogeneities and recruitability were quantified. Results:The first new densities developed after 8.4 ± 6.3 h (mean ± SD), and their number increased exponentially up to 15 ± 12 h. Afterward, they merged into full lung edema. A median of 61% (interquartile range, 57 to 76) of the lesions appeared in subpleural regions, 19% (interquartile range, 11 to 23) were peribronchial, and 19% (interquartile range, 6 to 25) were parenchymal (P < 0.0001). All the new densities were fully recruitable. Lung elastance and gas exchange deteriorated significantly after 18 ± 11 h, whereas lung edema developed after 20 ± 11 h. Conclusions:Most of the computed tomography scan new densities developed in nonhomogeneous lung regions. The damage in this model was primarily located in the interstitial space, causing alveolar collapse and consequent high recruitability.

Visceral artery aneurysms in liver transplant candidates and in patients after liver transplantation.

There are only few reviews concerning visceral aneurysms in cirrhotics, and a small number of papers on visceral aneurysms in liver transplant patients. The present paper investigates this condition in both groups of patients in a 10-year-retrospective study.

IROA: International Register of Open Abdomen, preliminary results

BackgroundNo definitive data about open abdomen (OA) epidemiology and outcomes exist. The World Society of Emergency Surgery (WSES) and the Panamerican Trauma Society (PTS) promoted the International Register of Open Abdomen (IROA).MethodsA prospective observational cohort study including patients with an OA treatment. Data were recorded on a web platform (Clinical Registers®) through a dedicated website: www.clinicalregisters.org.ResultsFour hundred two patients enrolled. Adult patients: 369 patients; Mean age: 57.39±18.37; 56% male. OA indication: Peritonitis (48.7%), Trauma (20.5%), Vascular Emergencies/Hemorrhage (9.4%), Ischemia (9.1%), Pancreatitis (4.2%),Post-operative abdominal-compartment-syndrome (3.9%), Others (4.2%). The most adopted Temporary-abdominal-closure systems were the commercial negative pressure ones (44.2%). During OA 38% of patients had complications; among them 10.5% had fistula. Definitive closure: 82.8%; Mortality during treatment: 17.2%. Mean duration of OA: 5.39(±4.83) days; Mean number of dressing changes: 0.88(±0.88). After-closure complications: (49.5%) and Mortality: (9%). No significant associations among TACT, indications, mortality, complications and fistula. A linear correlationexists between days of OA and complications (Pearson linear correlation = 0.326 p<0.0001) and with the fistula development (Pearson = 0.146 p= 0.016).Pediatric patients: 33 patients. Mean age: 5.91±(3.68) years; 60% male. Mortality: 3.4%; Complications: 44.8%; Fistula: 3.4%. Mean duration of OA: 3.22(±3.09) days.ConclusionTemporary abdominal closure is reliable and safe. The different techniques account for different results according to the different indications. In peritonitis commercial negative pressure temporary closure seems to improve results. In trauma skin-closure and Bogotà-bag seem to improve results.Trial registrationClinicalTrials.gov NCT02382770

A giant adrenal myelolipoma in a beta-thalassemia major patient: Does ineffective erythropoiesis play a role?

A 40-year-old thalassemia major (genotype b0 cod39/b1 IVSI-110) patient, regularly transfused with three units of packed red cells every three weeks with an average pre-transfusion hemoglobin level of 100 g/L, presented in 2002 with a right abdominal mass measuring 7.5 cm of maximum width found incidentally during the annual ultrasound (US) examination of the abdomen. A subsequent MRI showed radiological features suggestive for extramedullary hematopoiesis (EMH) thus the mass was periodically monitored. In 2009, because of the progressive increase in mass volume, hydroxyurea therapy was started at increasing dosage up to 15 mg/kg per day. In 2014 and 2015, a US evaluation showed a rapidly increasing volume of the abdominal mass. A computed tomography (CT) scan of the abdomen and pelvis with intravenous iodine contrast (Image 1) showed a huge well circumscribed retroperitoneal poly-lobed mass in the right abdomen measuring 19 3 15 3 25 cm, originating from the right adrenal gland and displacing the liver medially and the right kidney caudally and anteriorly; moreover, it compressed the inferior vena cava and displaced the mesenteric vessels. The mass was poorly vascularized with low contrast enhancement and marked heterogeneity, primarily due to the presence of fat tissue. At this time the radiological features were more suggestive of either an angiomyolipoma or a myelolipoma rather than EMH. Laparotomy was performed and a 3.5 kg encapsulated tumor (Image 1) attached to the right adrenal gland was removed. Gross examination showed a soft yellow to red cut surface with focal areas of hemorrhage. Extensive sampling was performed given the size of the mass and microscopic examination showed typical features of myelolipomas, with varying proportions of mature adipose tissue admixed with trilineage hematopoiesis (Image 1). A thin rim of residual adrenal tissue was present at the edge of the mass. Myelolipoma is a rare tumor that accounts for approximately the 4% of adrenal tumors. Some cases are associated with chronic hemolytic anemias or ineffective erythropoiesis, including both transfusion dependent and transfusion independent thalassemia [1–4], sickle cell anemia [5,6], and hereditary spherocytosis [7,8]. In a few cases the diagnosis of myelolipoma allowed the retrospective diagnosis of the underlying congenital anemia [5,8]. These associations suggest that the tumor is under the control of hematopoietic stimuli. It has been demonstrated that the first hematopoietic activity, known as primitive hematopoiesis, appears in the blood islands of the yolk sac. However, the first hematopoietic stem cells (HSC), defined by their capacity for long-term and multi-lineage engraftment in adult recipients, appear in the mammal embryo in the (AGM) region, and then home to the fetal liver [9,10]. We demonstrated by flow cytometry that the mass of our patient contained erythroid precursors (Image 1). Hence, residual HSC in organs derived from the AGM region in patients with ineffective erythropoiesis might be the source of the tumor mass. In our cohort of 190 patients affected by transfusion dependent thalassemia, we observed four cases of myelolipoma, three originating from the adrenal glands and one from the pelvic region. Further investigations involving a greater number of patients are needed to establish the prevalence of a tumor that might be underestimated in patients affected by diseases with chronic anemia and ineffective erythropoiesis.

Preliminary experience on hypothermic oxygenated machine perfusion in an Italian Liver Transplant Center

BACKGROUND Machine perfusion is increasingly utilized in liver transplantation to face the detrimental consequences of the use of extended-criteria donors. Hypothermic oxygenated machine perfusion (HOPE) appears to be more protective relative to static cold storage. Conversely, normothermic machine perfusion (NMP) allows a better graft evaluation. We describe a pilot prospective study on machine perfusion in selected grafts. METHODS HOPE was executed for all the grafts procured from donors after cardiac death (DCDs) and for livers from donors after brain death (DBDs) requiring prolonged preservation time. NMP was used when a more precise evaluation was needed. Both HOPE and NMP were performed through the portal vein and hepatic artery. RESULTS From July 2016 to November 2017, we performed 7 HOPE procedures: 5 for DCD and 2 for DBD grafts. Two livers presented with macrovesicular steatosis >30% (1 DCD and 1 DBD). HOPE lasted 240 minutes (180-320 min) with a total ischemia time of 575 minutes (410-810 min). Six grafts were successfully transplanted. One DCD graft required additional evaluation using NMP. The graft was then discarded due to extensive hepatocellular necrosis. In the post-transplant course, acute and chronic renal failure were the main complications affecting 3 and 2 recipients, respectively. In our series, steatosis was the main risk factor for kidney injury. Patient and graft survival rate was 100% and no ischemic cholangiopathies were observed after 270 days (106-582 days). CONCLUSIONS Our study confirms HOPE safety and efficacy for DCD and DBD grafts. These data are particularly significant for DCD management in the Italian setting where the mandatory 20-minute hands-off interval before death declaration further prolongs warm ischemia time.

OATPB1/B3 and MRP3 expression in hepatocellular adenoma predicts Gd-EOB-DTPA uptake and correlates with risk of malignancy

Hepatobiliary phase (HBP) Gd‐EOB‐DTPA‐enhanced magnetic resonance imaging (MRI) has increased the accuracy in differentiating focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA). However, the ability of this technique to distinguish HCA subtypes remains controversial. The aim of this study was to investigate the expression of hepatocyte transporters (OATPB1/B3, MRP2, MRP3) in HCA subtypes, hence to understand their MRI signal intensity on HBP Gd‐EOB‐DTPA‐enhanced MRI.

Open abdomen and entero-atmospheric fistulae: An interim analysis from the International Register of Open Abdomen (IROA)

INTRODUCTION No definitive data describing associations between cases of Open Abdomen (OA) and Entero-atmospheric fistulae (EAF) exist. The World Society of Emergency Surgery (WSES) and the Panamerican Trauma Society (PTS) thus analyzed the International Register of Open Abdomen (IROA) to assess this question. MATERIAL AND METHODS A prospective analysis of adult patients enrolled in the IROA. RESULTS Among 649 adult patients with OA 58 (8.9%) developed EAF. Indications for OA were peritonitis (51.2%) and traumatic-injury (16.8%). The most frequently utilized temporary abdominal closure techniques were Commercial-NPWT (46.8%) and Bogotà-bag (21.9%). Mean OA days were 7.9 ± 18.22. Overall mortality rate was 29.7%, with EAF having no impact on mortality. Multivariate analysis associated cancer (p = 0.018), days of OA (p = 0.003) and time to provision-of-nutrition (p = 0.016) with EAF occurrence. CONCLUSION Entero-atmospheric fistulas are influenced by the duration of open abdomen treatment and by the nutritional status of the patient. Peritonitis, intestinal anastomosis, negative pressure and oral or enteral nutrition were not risk factors for EAF during OA treatment.

Erratum to: IROA: International Register of Open Abdomen, preliminary results

[This corrects the article DOI: 10.1186/s13017-017-0123-8.].