Peritoneal adhesions represent an important clinical challenge in gastrointestinal surgery. Peritoneal adhesions are a consequence of peritoneal irritation by infection or surgical trauma, and may be ...considered as the pathological part of healing following any peritoneal injury, particularly due to abdominal surgery. The balance between fi brin deposition and degradation is critical in determining normal peritoneal healing or adhesion formation. Postoperative peritoneal adhesions are a major cause of morbidity resulting in multiple complications, many of which may manifest several years after the initial surgical procedure. In addition to acute small bowel obstruction, peritoneal adhesions may cause pelvic or abdominal pain, and infertility. In this paper, the authors reviewed the epidemiology, pathogenesis and various prevention strategies of adhesion formation, using Medline and PubMed search. Several preventive agents against postoperative peri-toneal adhesions have been investigated. Their role aims in activating fi brinolysis, hampering coagulation, diminishing the inflammatory response, inhibiting col-lagen synthesis or creating a barrier between adjacentwound surfaces. Their results are encouraging but most of them are contradictory and achieved mostly in animal model. Until additional fi ndings from future clinical researches, only a meticulous surgery can be recommended to reduce unnecessary morbidity and mortality rates from these untoward effects of surgery. In the current state of knowledge, pre-clinical or clini-cal studies are still necessary to evaluate the effective-ness of the several proposed prevention strategies of postoperative peritoneal adhesions.
Over the past decade, the clinical application of mesenchymal stromal cells (MSCs) has generated growing enthusiasm as an innovative cell-based approach in solid organ transplantation (SOT). These ...expectations arise from a significant number of both transplant- and non–transplant-related experimental studies investigating the complex anti-inflammatory, immunomodulatory, and tissue-repair properties of MSCs. Promising preclinical results have prompted clinical trials using MSC-based therapy in SOT. In the present review, the general properties of MSCs are summarized, with a particular emphasis on MSC-mediated impact on the immune system and in the ischemic conditioning strategy. Next, we chronologically detail all clinical trials using MSCs in the field of SOT. Finally, we envision the challenges and perspectives of MSC-based cell therapy in SOT.
BACKGROUNDLaparoscopic cholecystectomy might be considered minor surgery, but it may result in severe postoperative pain. Subcostal transversus abdominis plane (TAP) block, which produces ...long-lasting supra-umbilical parietal analgesia, might improve analgesia after laparoscopic cholecystectomy.
OBJECTIVEWe investigated whether subcostal TAP block would reduce opioid consumption and pain after laparoscopic cholecystectomy in patients provided with multimodal analgesia.
DESIGNA randomised, placebo-controlled, double-blind study.
SETTINGThe study was conducted at a university teaching hospital from December 2017 to June 2018.
PATIENTSSixty patients scheduled for laparoscopic cholecystectomy were included. Anaesthesia and postoperative analgesia (etoricoxib, paracetamol, ketamine and dexamethasone) were standardised.
INTERVENTIONAfter induction of anaesthesia, patients were allocated into two groupsultrasound-guided bilateral subcostal TAP block with 20 ml of levobupivacaine 0.375% and epinephrine 5 μg ml or 0.9% saline with epinephrine 5 μg ml.
MAIN OUTCOME MEASURESOpioid consumption in the recovery room and during the first 24 h after surgery were recorded. Postoperative somatic and visceral pain scores, fatigue and nausea were measured. Intra-operative end-tidal concentrations of sevoflurane (FETSEVO) were also recorded.
RESULTSTwenty-four hour postoperative opioid consumption were similar in both groups21.2 mg (95% CI 15.3 to 27.1) vs. 25.2 (95% CI 15.1 to 35.5) oral morphine equivalent in the levobupivacaine and 0.9% saline groups, respectively; P = 0.48. No significant between-group differences were observed with regards to parietal (P = 0.56) and visceral (P = 0.50) pain scores, fatigue and nausea. FETSEVO was slightly lower in the levobupivacaine group (P < 0.01).
CONCLUSIONSubcostal TAP block does not improve the analgesia provided by multimodal analgesia after laparoscopic cholecystectomy. It allows for a small reduction in intra-operative sevoflurane requirements.
TRIAL REGISTRATIONNCT0339153
Thiamine (vitamin B1) is an essential molecule for all life forms because thiamine diphosphate (ThDP) is an indispensable cofactor for oxidative energy metabolism. The less abundant thiamine ...monophosphate (ThMP), thiamine triphosphate (ThTP) and adenosine thiamine triphosphate (AThTP), present in many organisms, may have still unidentified physiological functions. Diseases linked to thiamine deficiency (polyneuritis, Wernicke-Korsakoff syndrome) remain frequent among alcohol abusers and other risk populations. This is the first comprehensive study on the distribution of thiamine derivatives in human biopsies, body fluids and cell lines.
Thiamine derivatives were determined by HPLC. In human tissues, the total thiamine content is lower than in other animal species. ThDP is the major thiamine compound and tissue levels decrease at high age. In semen, ThDP content correlates with the concentration of spermatozoa but not with their motility. The proportion of ThTP is higher in humans than in rodents, probably because of a lower 25-kDa ThTPase activity. The expression and activity of this enzyme seems to correlate with the degree of cell differentiation. ThTP was present in nearly all brain and muscle samples and in ∼60% of other tissue samples, in particular fetal tissue and cultured cells. A low (ThTP+ThMP)/(Thiamine+ThMP) ratio was found in cardiovascular tissues of patients with cardiac insufficiency. AThTP was detected only sporadically in adult tissues but was found more consistently in fetal tissues and cell lines.
The high sensitivity of humans to thiamine deficiency is probably linked to low circulating thiamine concentrations and low ThDP tissue contents. ThTP levels are relatively high in many human tissues, as a result of low expression of the 25-kDa ThTPase. Another novel finding is the presence of ThTP and AThTP in poorly differentiated fast-growing cells, suggesting a hitherto unsuspected link between these compounds and cell division or differentiation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IMPORTANCE: The option of donating organs after euthanasia is not well known. Assessment of the results of organ transplants with grafts donated after euthanasia is essential to justify the use of ...this type of organ donation. OBJECTIVES: To assess the outcomes of liver transplants (LTs) with grafts donated after euthanasia (donation after circulatory death type V DCD-V), and to compare them with the results of the more commonly performed LTs with grafts from donors with a circulatory arrest after the withdrawal of life-supporting treatment (type III DCD-III). DESIGN, SETTING, AND PARTICIPANTS: This retrospective multicenter cohort study analyzed medical records and LT data for most transplant centers in the Netherlands and Belgium. All LTs with DCD-V grafts performed from the start of the donation after euthanasia program (September 2012 for the Netherlands, and January 2005 for Belgium) through July 1, 2018, were included in the analysis. A comparative cohort of patients who received DCD-III grafts was also analyzed. All patients in both cohorts were followed up for at least 1 year. Data analysis was performed from September 2019 to December 2019. EXPOSURES: Liver transplant with either a DCD-V graft or DCD-III graft. MAIN OUTCOMES AND MEASURES: Primary outcomes were recipient and graft survival rates at years 1, 3, and 5 after the LT. Secondary outcomes included postoperative complications (early allograft dysfunction, hepatic artery thrombosis, and nonanastomotic biliary strictures) within the first year after the LT. RESULTS: Among the cohort of 47 LTs with DCD-V grafts, 25 organ donors (53%) were women and the median (interquartile range IQR) age was 51 (44-59) years. Among the cohort of 542 LTs with DCD-III grafts, 335 organ donors (62%) were men and the median (IQR) age was 49 (37-57) years. Median (IQR) follow-up was 3.8 (2.1-6.3) years. In the DCD-V cohort, 30 recipients (64%) were men, and the median (IQR) age was 56 (48-64) years. Recipient survival in the DCD-V cohort was 87% at 1 year, 73% at 3 years, and 66% at 5 years after LT. Graft survival among recipients was 74% at 1 year, 61% at 3 years, and 57% at 5 years after LT. These survival rates did not differ statistically significantly from those in the DCD-III cohort. Incidence of postoperative complications did not differ between the groups. For example, the occurrence of early allograft dysfunction after the LT was found to be 13 (31%) in the DCD-V cohort and 219 (45%) in the DCD-III cohort. The occurrence of nonanastomotic biliary strictures after the LT was found to be 7 (15%) in the DCD-V cohort and 83 (15%) in the DCD-III cohort. CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that LTs with DCD-V grafts yield similar outcomes as LTs with DCD-III grafts; therefore, grafts donated after euthanasia may be a justifiable option for increasing the organ donor pool. However, grafts from these donations should be considered high-risk grafts that require an optimal donor selection process and logistics.
Introduction
Mesenchymal stromal cells (MSCs) have particular properties that are of interest in organ transplantation, including the expansion of regulatory T cells (Tregs), a key factor in ...transplant tolerance induction. However, the most effective immunosuppressive drug to associate with MSCs has yet to be defined. Additionally, the impact of the association of everolimus with MSCs on Treg expansion, and on the induction of liver graft tolerance, has never been studied. The aim of this study was to evaluate the effects of MSCs in combination, or not, with everolimus on Treg expansion and in a model of rejection after liver transplantation (LT) in the rat.
Methods
Firstly, 24 Lewis rats were assigned to 4 groups (n=6 in each group) receiving intravenous MSCs or saline injection at day (D)9 with/without subcutaneous everolimus from D0 to D14. Analysis of circulating Tregs was performed at D0, D14 and D28. In a second set of experiment, 30 Lewis rats were randomized in 3 groups 48hours after LT with a Dark Agouti rat liver: everolimus (subcutaneous for 14 days), MSCs (intravenous injection at post-operative day 2 and 9), or both everolimus and MSCs. Rejection of the liver graft was assessed by liver tests, histology and survival.
Results
Individually, MSC infusion and everolimus promoted Treg expansion in rats, and everolimus had no negative impact on Treg expansion in combination with MSCs. However, in the LT model, injections of MSCs two and nine days following LT were not effective at preventing acute rejection, and the combination of MSCs with everolimus failed to show any synergistic effect when compared to everolimus alone.
Conclusion
Everolimus may be used in association with MSCs. However, in our model of LT in the rat, post-transplant MSC injections did not prevent acute rejection, and the association of MSCs with everolimus did not show any synergistic effect.
Ischemia/reperfusion injury (IRI) represents a worldwide public health issue of increasing incidence. IRI may virtually affect all organs and tissues and is associated with significant morbidity and ...mortality. Particularly, the duration of blood supply deprivation has been recognized as a critical factor in stroke, hemorrhagic shock, or myocardial infarction, as well as in solid organ transplantation (SOT). Pathophysiologically, IRI causes multiple cellular and tissular metabolic and architectural changes. Furthermore, the reperfusion of ischemic tissues induces both local and systemic inflammation. In the particular field of SOT, IRI is an unavoidable event, which conditions both short- and long-term outcomes of graft function and survival. Clinically, the treatment of patients with IRI mostly relies on supportive maneuvers since no specific target-oriented therapy has been validated thus far. In the present review, we summarize the current literature on mesenchymal stromal cells (MSC) and their potential use as cell therapy in IRI. MSC have demonstrated immunomodulatory, anti-inflammatory, and tissue repair properties in rodent studies and in preliminary clinical trials, which may open novel avenues in the management of IRI and SOT.
PDF
