Objectives
Cirrhotic children wait‐listed for liver transplant are prone to bleeding from gastrointestinal varices. Grade 2‐3 esophageal varices, red signs, and gastric varices are well‐known risk ...factors. However, the involvement of hemostatic factors remains controversial because of the rebalanced state of coagulation during cirrhosis.
Methods
Children suffering from decompensated cirrhosis were prospectively included while being on waitlist. Portal hypertension was assessed by ultrasound and endoscopy. Coagulopathy was evaluated through conventional tests, thromboelastometry, and platelet function testing. The included children were followed up until liver transplantation, and all bleeding episodes were recorded. Children with or without bleeding were compared according to clinical, radiological, endoscopic, and biological parameters. In addition, validation of a predictive model for risk of variceal bleeding comprising of grade 2‐3 esophageal varices, red spots, and fibrinogen level <150 mg/dL was applied on this cohort.
Results
Of 20 enrolled children, 6 had upper gastrointestinal bleeding. Significant differences were observed in fibrinogen level, adenosine diphosphate, and thrombin‐dependent platelet aggregation. The model used to compute the upper gastrointestinal bleeding risk had an estimated predictive performance of 81.0%. Platelet aggregation analysis addition improved the estimated predictive performance up to 89.0%.
Conclusions
We demonstrated an association between hemostatic factors and the upper gastrointestinal bleeding risk. A low fibrinogen level and platelet aggregation dysfunction may predict the risk of bleeding in children with decompensated cirrhosis. A predictive model is available to assess the upper gastrointestinal bleeding risk but needs further investigations.
Clinicaltrials.gov number: NCT03244332
Stem cells from extra-or intrahepatic sources have been recently characterized and their usefulness for the generation of hepatocyte-like lineages has been demonstrated. Therefore, they are being ...increasingly considered for future applications in liver cell therapy. In that field, liver cell transplantation is currently regarded as a possible alternative to whole organ transplantation, while stem cells possess theoretical advantages on hepatocytes as they display higher in vitro culture performances and could be used in autologous transplant procedures. However, the current research on the hepatic fate of stem cells is still facing difficulties to demonstrate the acquisition of a full mature hepatocyte phenotype, both in vitro and in vivo. Furthermore, the lack of obvious demonstration of in vivo hepatocyte-like cell functionality remains associated to low repopulation rates obtained after current transplantation procedures. The present review focuses on the current knowledge of the stem cell potential for liver therapy. We discuss the characteristics of the principal cell candidates and the methods to demonstrate their hepatic potential in vitro and in vivo. We finally address the question of the future clinical applications of stem cells for liver tissue repair and the technical aspects that remain to be investigated.
Cell therapy, in particular liver cell transplantation, holds great therapeutic potential and is partially hindered by the high rate of apoptosis during cell isolation, cryopreservation, and ...engraftment. Apoptosis occurring due to cell detachment from the extracellular matrix is a phenomenon termed “anoikis. ” The purpose of this review is to describe signaling mechanisms pertinent to anoikis in both immortalized cell lines, but particularly in primary normal epithelial cells. The mechanisms described include integrin signaling and survival molecules, caspase activation, and the role of mitochondrial proteins in anoikis. Strategies to prevent anoikis during isolation and cryopreservation of hepatocytes are discussed.
Accelerated step-up or anti-tumor necrosis factor (TNF) before first remission is currently not recommended in pediatric Crohn's disease.
Five-year follow-up data from a prospective observational ...cohort of children diagnosed with Crohn's disease in Belgium were analyzed. Disease severity was scored as inactive, mild, or moderate to severe. Remission or inactive disease was defined as sustained if lasting ≥2 years. Univariate analyses were performed between anti-TNF-exposed versus naive patients and anti-TNF before versus after first remission and correlations assessed with primary outcomes average disease severity and sustained remission.
A total of 91 patients (median IQR age 12.7 10.9-14.8 yrs, 53% male) were included. Disease location was 12% L1, 23% L2, and 64% L3 with 76% upper gastrointestinal and 30% perianal involvement. Disease severity was 25% mild and 75% moderate to severe. Of 66 (73%) anti-TNF-exposed patients, 34 (52%) had accelerated step-up. Anti-TNF use was associated with age (13.1 11.5-15.2 versus 11.8 8.7-13.8 yrs; P < 0.05), L2 (29% versus 8%; P = 0.04), and average disease severity (1.7 1.4-1.9 versus 1.4 1.3-1.6; P < 0.001). Duration of anti-TNF correlated with average disease severity (r = 0.32, P = 0.002). Accelerated step-up was also associated with age (13.3 12.1-15.9 versus 12.5 10.2-14.1; P = 0.02) and average disease severity (1.8 1.6-1.9 versus 1.6 1.3-1.8; P = 0.002). Duration of sustained remission was similar in all patients, and no serious infections, cancer, or deaths were reported.
Anti-TNF therapy and accelerated step-up in older patients with more severe disease leads to beneficial long-term outcomes.
vWFpp/ADAMTS13 ratio should be further studied as a useful marker for diagnosis of thrombotic microangiopathy postliver transplantation. Immunosuppressive regimen modification and plasma ...supplementation can lead to recovery.
vWFpp/ADAMTS13 ratio should be further studied as a useful marker for diagnosis of thrombotic microangiopathy postliver transplantation. Immunosuppressive regimen modification and plasma supplementation can lead to recovery.
Summary
Aims
The aim of this study was to evaluate the usability and safety of the Explorer Endoscopy Mask® (EM) as an alternative to endotracheal intubation in children undergoing elective ...esogastroduodenoscopy (EGD) under general anesthesia (GA).
Methods
This study was a retrospective observational study. The study was undertaken at the pediatric digestive endoscopy suite in the Cliniques universitaires Saint‐Luc, Brussels, Belgium. We retrospectively analyzed the occurrence of minor and major airway‐related adverse effects during pediatric EGD procedures performed under GA with the EM between June 2014 and March 2015.
Results
During the study period, 173 patients underwent EGD. Their mean age was 8.4 years (median: 9.1 years, range 4 months to 16 years). Mean duration of endoscopy (from insertion to removal of the endoscope) was 12.6 min (median: 12 min, range 3–47 min). The use of EM was uneventful in 159 (92%) cases. There were 24 airway‐related adverse events in 14 children. Hypoxemia (SpO2 <90%) (13 events, 7.5%) was the most commonly encountered complication followed by laryngo‐ or bronchospasm (five events, 2.89%), cough (five events, 2.89%), and intubation (one event, 0.58%). No cases of regurgitation/aspiration were observed.
Conclusions
Our data support the EM use in pediatric EGD. There were few transient respiratory adverse events which were easily solved with minor interventions.
Transplantation of human hepatocytes has recently been demonstrated as a safe alternative to partially correct liver inborn errors of metabolism. Cryopreservation remains the most appropriate way of ...cell banking. However, mitochondrial-mediated apoptosis has been reported after cryopreservation and little is known on the involved molecular mechanisms. The aim of this study was to investigate mitochondrial functions of freshly isolated and cryopreserved/thawed hepatocytes from mice and humans. We report here that cryopreservation induced a dramatic drop of ATP levels in hepatocytes. The oxygen consumption rate of cryopreserved/thawed hepatocytes was significantly lower compared to fresh cells. In addition, the uncoupling effect of 2,4-dinitrophenol was lost, in parallel with a reduction of mitochondrial membrane potential. Furthermore, a decrease in mitochondrial respiratory rate was evidenced on permeabilized hepatocytes in the presence of substrate for the respiratory chain complex 1. Interestingly, this effect was less marked with a substrate for complex 2. Electron microscopy examination indicated that mitochondria were swollen and devoid of cristae after cryopreservation. These changes could explain the cytosolic release of the proapoptotic protein cytochrome c in cryopreserved cells. Nevertheless, no caspase 9-3 activation and only few apoptotic and necrotic cells were found, indicating that the subsequent cell death program was not yet evidenced. Our results demonstrate that cryopreservation of hepatocytes induced alteration of the mitochondrial machinery. They also suggest that, in addition to technical progress in the cryopreservation procedure, protection of the respiratory chain complex 1 should be considered to improve the quality of cryopreserved hepatocytes.
Internalizing Motivation to Self-Care Aujoulat, Isabelle; Janssen, Magda; Libion, France ...
Qualitative health research,
03/2014, Letnik:
24, Številka:
3
Journal Article
Recenzirano
The transition from parent-controlled care to self-managed care represents an important challenge for adolescents with chronic conditions. We sought to gain a deeper understanding of the factors ...influencing the internalization of motivation to self-care in adolescent liver transplant recipients. We conducted a qualitative study using in-depth interviews with 18 young patients. We triangulated the data collected from the patients with data from parents and health care providers, and used an inductive approach to analyze the data. Our results illustrate three interrelated challenges that impact on young patients’ motivation to self-care: (a) the cognitive challenge of fully understanding one’s condition and personal health risks; (b) the behavioral challenge of developing independence regarding self-management issues; and (c) the psychological challenge of building a sense of self-ownership and purpose. The latter involves overcoming the trauma of survival and coming to terms with feelings of obligation, two challenges inherent to transplantation that warrant further investigation.
PDF
