Perfusion of isolated rat kidney with Mesenchymal Stromal Cells/Extracellular Vesicles prevents ischaemic injury

Kidney donation after circulatory death (DCD) is a less than ideal option to meet organ shortages. Hypothermic machine perfusion (HMP) with Belzer solution (BS) improves the viability of DCD kidneys, although the graft clinical course remains critical. Mesenchymal stromal cells (MSC) promote tissue repair by releasing extracellular vesicles (EV). We evaluated whether delivering MSC-/MSC-derived EV during HMP protects rat DCD kidneys from ischaemic injury and investigated the underlying pathogenic mechanisms. Warm ischaemic isolated kidneys were cold-perfused (4 hrs) with BS, BS supplemented with MSC or EV. Renal damage was evaluated by histology and renal gene expression by microarray analysis, RT-PCR. Malondialdehyde, lactate, LDH, glucose and pyruvate were measured in the effluent fluid. MSC-/EV-treated kidneys showed significantly less global ischaemic damage. In the MSC/EV groups, there was up-regulation of three genes encoding enzymes known to improve cell energy metabolism and three genes encoding proteins involved in ion membrane transport. In the effluent fluid, lactate, LDH, MDA and glucose were significantly lower and pyruvate higher in MSC/EV kidneys as compared with BS, suggesting the larger use of energy substrates by MSC/EV kidneys. The addition of MSC/EV to BS during HMP protects the kidney from ischaemic injury by preserving the enzymatic machinery essential for cell viability and protects the kidney from reperfusion damage

Physiological parameters for Prognosis in Abdominal Sepsis (PIPAS) Study : a WSES observational study

BackgroundTiming and adequacy of peritoneal source control are the most important pillars in the management of patients with acute peritonitis. Therefore, early prognostic evaluation of acute peritonitis is paramount to assess the severity and establish a prompt and appropriate treatment. The objectives of this study were to identify clinical and laboratory predictors for in-hospital mortality in patients with acute peritonitis and to develop a warning score system, based on easily recognizable and assessable variables, globally accepted.MethodsThis worldwide multicentre observational study included 153 surgical departments across 56 countries over a 4-month study period between February 1, 2018, and May 31, 2018.ResultsA total of 3137 patients were included, with 1815 (57.9%) men and 1322 (42.1%) women, with a median age of 47years (interquartile range [IQR] 28-66). The overall in-hospital mortality rate was 8.9%, with a median length of stay of 6days (IQR 4-10). Using multivariable logistic regression, independent variables associated with in-hospital mortality were identified: age > 80years, malignancy, severe cardiovascular disease, severe chronic kidney disease, respiratory rate >= 22 breaths/min, systolic blood pressure 4mmol/l. These variables were used to create the PIPAS Severity Score, a bedside early warning score for patients with acute peritonitis. The overall mortality was 2.9% for patients who had scores of 0-1, 22.7% for those who had scores of 2-3, 46.8% for those who had scores of 4-5, and 86.7% for those who have scores of 7-8.ConclusionsThe simple PIPAS Severity Score can be used on a global level and can help clinicians to identify patients at high risk for treatment failure and mortality.Peer reviewe

THALLIUM-201 MYOCARDIAL PERFUSION IMAGING IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

The cardiovascular system is frequently affected in systemic lupus erythematosus (SLE). The observation of clinical manifestations related to the presence of coronary artery disease has not been frequently documented in young SLE patients. In these patients, the presence of inflammatory or thrombotic vascular lesions is often documented by anatomo-histological studies in the absence of previous clinical manifestations. The purpose of this study was to evaluate the presence of myocardial perfusion defects in SLE patients. The study was carried out in 15 patients without clinical signs of myocardial ischemia, 1 male and 14 females, 24 to 64 years old, with a mean SLE duration of 10.2 +/- 7.5 years. All the patients had normal blood pressure; electrocardiogram and Doppler-echocardiographic analysis showed values in the normal range. All the patients underwent thallium-201 exercise stress imaging repeated 3 hours later at rest, with tomographic SPECT analysis. Exercise test was carried out until submaximal load, without induction of ST segment alterations or symptoms. Scintigraphic scan showed normal thallium-201 SPECT imaging in 11/15 patients, while the other 4 patients had a slight perfusion defect, 3 of them in the inferior segment, in 2 non reversible and in 1 reversible; 1 patient had a non reversible defect in the septal segment. These slight perfusion defects, prevalently non reversible, may sometimes be a false positive imaging. Our results are in contrast with the literature observations concerning the frequent incidence of thallium-201 perfusion defects in SLE patients. In young asymptomatic SLE patients, our study does not report very important data indicating myocardial ischemia and suggesting the presence of significant coronary obstruction or vasculitis

Operating Room Setup: How to Improve Health Care Professionals Safety During Pandemic COVID-19-A Quality Improvement Study

Background:COVID-19 is a terrific pandemic and a potential risk for every health care professional (HCP), especially during emergency conditions where the right timing is essential for the correct treatment. During surgery the correct setting of operative room (OR) is mandatory to reduce the risk of contamination. Personal protection equipment (PPE), specific devices, and planned OR setting are essential during surgery in pandemic COVID-19. Methods:Medline, PubMed, Scientific societies recommendations, and guidelines were consulted to identify articles reporting the setup of OR during pandemic COVID-19. Results:OR must have a high-efficiency particulate air (HEPA) filter with negative pressure and a high air exchange cycle rate. Every supply kit should be packed and placed in the OR before patient arrival. A detailed checklist of equipment and devices is necessary. Personal PPE at the highest level should be provided to every HCP (Association of the Advancement of Medical Instrumentation [AAMI]-Level-III surgical gowns; double latex-free gloves with Acceptable Quality Level <1.0; FFP3 or powered air-purifying respirator masks with face shield). Anesthesia should be performed with a rapid sequence intubation. During surgery energy devices should be settled to the lower level in combination with a smoke evacuation switch pen with disposable smoke evacuation HEPA filter to minimize surgical smoke spread. During laparoscopy low pneumoperitoneum pressures and aspiration systems must be provided. Conclusions:Emergency surgery during pandemic COVID-19 increases the risk for every HCP in the OR. A theoretical risk of transmission from the surgical field exists. It is mandatory the adoption of strong strategies to reduce the risk of contamination in the OR

Kidney transplant rejection rate in screened patients for anti-SARS-CoV-2 antibodies, during COVID-19 pandemic in Northern Italy

Coronavirus is a high-risk pathogen for kidney transplant recipients receiving immunosuppressive therapy; Coronavirus disease 2019 (COVID-19) is an infection causing severe acute respiratory syndrome (SARS-CoV2), and progressive withdrawal of immunosuppressive drugs has been suggested in transplanted patients. At IRCCS San Matteo Hospital in Pavia, Northern Italy, during the pandemic we performed a screening and all transplanted patients were evaluated for IgG anti SARS-CoV-2; 12 of 201 kidney transplant recipients (6%) screened for IgG anti SARS-CoV-2 (s) developed kidney transplant rejection; 10 (83%) were negative and 2 (17%) resulted positive for SARS-CoV-2 IgG, while among 189 patients without rejection, 162 (86%) resulted negative and 27 (14%) positive (P=0.69). COVID 19 course may be more severe in kidney transplant recipients but it does not significantly increase risk of kidney rejection

Francia y la Guerra de la Independencia en 1808 (de Bailén a Chamartín): la información y la acción

Ann. It. Med. Int

Understanding Bone Damage After Kidney Transplantation: A\ua0Retrospective Monocentric Cross Sectional Analysis

Background. Kidney transplantation (KT) immunosuppression may induce bone tissue damage with bone mineral density (BMD) loss increasing bone fractures risk. Steroid therapy is considered the major player, but others factors are still under review.Patients and Methods. We designed an observational retrospective cohort study to evaluate bone damage after KT. The prevalence of osteopenia, osteoporosis, bone fractures, and the associated risk factors were investigated. The following parameters were recorded before transplantation and at the last follow-up: demographic indexes, cumulative steroid dose (CSD), dialytic and transplantologic age, previous nephropathy, femoral and lumbar BMD, fractures, immunosuppressors, calcemia, phosphoremia, rejection episodes, estimated glomerular filtration rate, and parathyroid hormone and vitamin D levels. Stata software (Stata Corporation, College Station, Texas, United States) was used for the statistical analysis, to perform the Fisher's exact test, Kruskal-Wallis test, Student t test, as well as univariate and multivariate analyses.Results. The analyzed cohort was composed of 297 patients (65.3% males and 34.7% females). Sixty percent of KT patients had normal BMD, 24% had osteopenia, and 15% had osteoporosis. Twelve percent were victims of bone fractures (8.4% minor, 2% femoral, and 1.7% vertebral). A significant correlation (P <.05) was observed for both osteopenia and osteoporosis with menopause, transplantologic age, CSD, previous glomerulonephritis, and mammalian target of rapamycin (mTOR) inhibitors treatment (imTOR).Conclusion. This study confirms the correlation between CSD (both before and after transplantation) and post -transplantation bone damage. It also shows that a large fraction of these patients had normal BMD related with a low steroid dose in our protocols. This correlation between imTOR assumption and osteoporosis deserves attention and warrants further in vitro analyses to be performed

The role of therapeutic drug monitoring in the treatment of cytomegalovirus disease in kidney transplantation.

Cytomegalovirus (CMV) infection is a common complication following solid organ transplantation that may severely affect the outcome of transplantation. Ganciclovir (GCV) and its prodrug valganciclovir are successfully used to prevent and treat CMV infection; however, in a small percentage of patients, CMV gene mutations may lead to drug resistance. GCV resistance is defined as increasing CMV viremia or progressive clinical disease during prolonged antiviral therapy, due to CMV gene mutation. This has emerged as a new challenge, especially because alternative drugs such as cidofovir and foscarnet have a number of important side effects. Here we report the case of a kidney transplanted patient who experienced life-threatening CMV disease, which initially appeared to be GCV-resistant, but was instead found to be associated with inadequate antiviral drug levels. The patient was then successfully treated by monitoring plasma GCV levels. We suggest using plasma GCV monitoring in the management of all cases of critical CMV disease, in which GCV resistance is suspected