New Definitions of Sepsis and the Quest for Specific Biomarkers. Are the miRNAs the Answer?

Sepsis represents a systemic illness, characterized by life-threatening organ dysfunction induced by infection. Early diagnostic, evaluation of severity of sepsis with aggressive resuscitation and administration of appropriate antibiotics are associated with improved outcomes. In 2016 a new definition of sepsis (Sepsis-3) was proposed. The key element of sepsis-induced organ dysfunction is defined by "an acute change in total SOFA score >= 2 points consequent to infection". The use of SIRS criteria as identification of sepsis was abandoned and subcategory of severe sepsis was eliminated. A wide spectrum of biomarkers had been proposed for potential use in sepsis, more than in other diseases, outlying the complex pathophysiology of this condition. The first study reporting the clinical value of circulating miRNAs in sepsis showed that both leukocytes and plasma miR-150 levels are significantly reduced in sepsis patients compared with controls and correlate with sepsis severity. Several miRNAs were found differentially expressed in sepsis patients, but most of the published studies failed to find miRNA biomarkers that could differentiate sepsis from SIRS. A solution to this problem seems to be building and analyzing miRNA network in sepsis patients.

Gastric Cancer, Hemophilia A and Angiodysplasia - An Unreported Association with Clinical Implications in a Patient with Digestive Hemorrhage.

Introduction: Gastric cancer is a rare cause of upper digestive hemorrhage. Associated co-morbidities may have a detrimental effect on both early and long-term outcomes after surgery for gastric cancer. Association of gastric adenocarcinoma with hemophilia A and angiodysplasia was not previously reported, and the impact on postoperative outcome is not known. Case Report: A 49-year-old male with inherited hemophilia A presented with upper digestive hemorrhage and severe anemia, and was diagnosed with gastric carcinoma. The patient underwent total gastrectomy with splenectomy and D2 lymph nodes dissection. The postoperative outcome was complicated by digestive hemorrhage due to the presence of lesions of angiodysplasia of the cecum and jejunum that were successfully treated with coils mounted by the interventional radiologic approach. During the pre and postoperative periods, the patient received human coagulation factor VIII and developed auto-antibodies against factor VIII. Thus, human coagulation factor VIII administration was stopped and replaced with factor eight inhibitor bypassing activity (FEIBA). The patient was discharged at home on postoperative day 41, without any signs of bleeding. Conclusion: To the best of our knowledge, this is the first reported association of gastric adenocarcinoma, hemophilia A and angiodysplasia. All these lesions may lead to digestive hemorrhage and can pose very difficult problems of decision for diagnosis and therapy. A multidisciplinary approach including hematologist, surgeon, anesthesiologist, endoscopist and the interventional radiologist is mandatory to have a proper diagnosis and management for these patients.

The Romanian National Program for Liver Transplantation - 852 Procedures in 815 Patients over 17 Years (2000-2017): A Continuous Evolution to Success.

Background: Liver transplantation (LT) has become an established treatment for end-stage liver disease, with more than 20.000 procedures yearly worldwide. The aim of this study was to analyze the results of Romanian National Program of LT. Methods: Between April 2000 and April 2017, 817 pts received 852 LTs in Romania. Male/female ratio was 487/330, while adult/pediatric ratio was 753/64, with a mean age of 46 years (median 50 yrs; range 7 months - 68 yrs). Main LT indications were HBV cirrhosis (230 pts; 28.2%), HCC (173 pts; 21.2%), and HCV cirrhosis (137 pts; 16.8%). Waiting time and indications for LT, patient and donor demographics, graft features, surgical procedures, and short and long-term outcomes were analyzed. Results: DDLT was performed in 682 pts (83.9%): whole LT in 662 pts (81%), split LT in 16 pts (2.3%), reduced LT in 2 pts (0.2%), and domino LT in 1 pts (0.1%). LDLT was performed in 135 pts (16.5%): right hemiliver in 93 pts (11.4%), left lateral section in 28 pts (3.4%), left hemiliver in 8 pts (1%), left hemiliver with segment 1 in 4 pts (0.5%), and dual graft LDLT in 2 pts (0.2%). Overall major morbidity rate was 31.4% (268 pts), while perioperative mortality was 7.9% (65 pts). Retransplantation rate was 4.3% (35 pts): 27 whole LTs, 3 reduced LTs, 3 split LTs, and 2 LDLT. Long-term overall 1-, 3-, and 5-year estimated survival rates for patients were 87.9%, 81.5%, and 79.1%, respectively. One-, 3-, and 5-year overall mortality on waiting list also decreased significantly over time from 31.4%, 54.1% and 63.5%, to 4.4%, 13.9% and 23.6%, respectively. Conclusions: The Romanian National program for liver transplantation addresses all causes of acute and chronic liver failure or liver tumors in adults and children, using all surgical techniques, with good long-term outcome. The program constantly evolved over time, leading to decreased mortality rate on the waiting list.

Patients After Splenectomy: Old Risks and New Perspectives.

The risks that arise after splenectomy can be divided in infectious and non-infectious. The link between splenectomy and these hazards remains partially unknown. Host defense against infection is altered after splenectomy and such individuals develop sepsis more easily and the infection has a fulminant course. Splenectomy is also a potential risk factor for several vascular complications that result from partial or total obstruction of an arterial or venous blood vessel. Furthermore, pulmonary hypertensioncan be a severe and sometimes fatal complication following splenectomy. Some authors also consider that malignancies, diabetes mellitus and acute pancreatitis are non-infectious complications after splenectomy. The most feared complication for splenectomized patients remains sepsis. The pathophysiology of sepsis is still controversial. Death in sepsis can occur due to either hyper-inflammation or immune paralysis. Multiple experimental evidences link cellular and viral microRNAs with sepsis. We presume that miRNAs are also associated with the immunosuppression of the asplenic patients which leads to the high risk of deadly sepsis. Studying the expression level of circulating miRNAs in asplenic patients could help us better understand the postsplenectomy immunosuppression and develop new diagnostic and therapeutic tools.