When tissue injury results to breakage, platelets are not only involved in plug formation and wound sealing, but they also play an important role throughout the tissue recovery process. Specifically, ...platelets accumulate at the site of injury and release a large number of biologically active mediators at injury sites, which initiate or modulate damaged tissue regeneration. Moreover, extensive experimental evidence has elucidated the involvement of platelets in tumor growth and metastasis. As such, this mini-review aimed to highlight the relatively lesser known functions of platelets.
Preoperative neutrophil-lymphocyte ratio (NLR), has shown a predictive value in living donor liver transplantation (LDLT). However, the change in the NLR during LDLT has not been fully investigated. ...We aimed to compare graft survival between the NLR increase and decrease during LDLT. From June 1997 to April 2019, we identified 1292 adult LDLT recipients with intraoperative NLR change. The recipients were divided according to NLR change: 103 (8.0%) in the decrease group and 1189 (92.0%) in the increase group. The primary outcome was graft failure in the first year. In addition, variables associated with NLR change during LDLT were evaluated. During 1-year follow-up, graft failure was significantly higher in the decrease group (22.3% vs. 9.1%; hazard ratio 1.87; 95% confidence interval 1.10-3.18; p = 0.02), but postoperative complications did not differ between two groups. This finding was consistent for the overall follow-up. Variables associated with NLR decrease included preoperative NLR > 4, model for end-stage liver disease score, intraoperative inotropic infusion and red blood cell transfusion, and operative duration. The least absolute shrinkage and selection operator model yielded similar results. NLR decrease during LDLT appeared to be independently associated with graft survival. Further studies are needed to confirm our findings.
Despite various intraoperative thermal strategies, core heat loss is considerable during liver transplantation and hypothermia is common. We tested whether forced-air prewarming prevents hypothermia ...during liver transplantation. Adult patients undergoing living donor liver transplantation were randomly assigned to non-prewarming group (n = 20) or prewarming group (n = 20). Patients in prewarming group underwent 30-min forced-air warming before anesthetic induction. During surgery, core temperature was measured in the pulmonary artery. The primary outcome was intraoperative hypothermia (< 36.0 °C). The secondary outcomes included plasma lactate concentration. Intraoperative hypothermia risk was significantly lower in prewarming group than in non-prewarming group (60.0% vs. 95.0%, P = 0.020). The difference in hypothermia incidence between groups was greater in the post-induction phase (20.0% vs. 85.0%, P < 0.001) than in the anhepatic or post-reperfusion phase, suggesting that prewarming mainly acts on preventing post-induction core-to-peripheral heat redistribution. Hypothermia duration was significantly shorter in prewarming group (60 0-221 min vs. 383 108-426 min, P = 0.001). Lactate concentration decreased during 3 h after graft reperfusion in prewarming group, whereas it continuously increased in non-prewarming group (- 0.19 - 0.48 to 0.13 mmol/L vs. 1.17 3.31-0.77 mmol/L, P = 0.034). In conclusion, forced-air prewarming decreases the incidence and duration of intraoperative hypothermia with potential clinical benefit while mainly acting by preventing the core-to-peripheral heat redistribution.Clinical trial registration: Registered at the Clinical Research Information Service ( https://cris.nih.go.kr , KCT0003230) on 01/10/2018.
Pure laparoscopic donor right hepatectomy (PLDRH) is not a standard procedure for living donor liver transplantation but is safe and reproducible in the hands of experienced surgeons. However, the ...perioperative outcomes of PLDRH have not been fully evaluated yet. We used propensity score matching to compare the perioperative complications and postoperative short-term outcomes of donors undergoing PLDRH and open donor right hepatectomy (ODRH). A total of 325 consecutive donors who underwent elective, adult-to-adult right hepatectomy were initially screened. After propensity score matching, all patients were divided into two groups: PLDRH (n = 123) and ODRH (n = 123) groups. Perioperative complications and postoperative outcomes were compared between the two groups. Postoperative pulmonary complications were significantly more common in the ODRH than in the PLDRH group (54.5 vs. 31.7%, P < 0.001). The biliary complications (leak and stricture) were higher in PLDRH group than in the ODRH group (8% vs. 3%), but it failed to reach statistical significance (P = 0.167). Overall, surgical complication rates were similar between the two groups (P = 0.730). The opioid requirement during the first 7 postoperative days was higher in the ODRH group (686 vs. 568 mg, P < 0.001). The hospital stay and time to the first meal were shorter in the PLDRH than in the ODRH group (P = 0.003 and P < 0.001, respectively). PLDRH reduced the incidence of postoperative pulmonary complications and afforded better short-term postoperative outcomes compared to ODRH. However, surgical complication rates were similar in both groups.
OBJECTIVE:To evaluate the association between anesthetic management before and after graft reperfusion and early graft regeneration in living donor liver transplantation (LDLT).
BACKGROUND:Sufficient ...graft regeneration is essential for the success of LDLT. Diverse signals start to trigger liver regeneration immediately after graft reperfusion.
METHODS:Graft volume at 14 ± 2 days after LDLT was measured in 379 consecutive recipients using computed tomography images with 3-dimensional reconstruction. The association between anesthetic variables and the degree of graft regeneration for 2 weeks was analyzed using simple and multiple linear regressions. The anesthetic variables included hemodynamics, laboratory measurements, vasoactive drugs, and blood products transfusion.
RESULTS:The degree of graft regeneration for 2 weeks was 52% in median and ranged from 5% to 123%. Platelet transfusion was identified as the sole independent anesthetic factor contributing to graft regeneration. Platelet concentrate transfusion of 1 to 6 units vs none was correlated with a 6.5% increase in graft regeneration (P = 0.012). Platelet concentrate transfusion of more than 6 units vs none was further correlated with an 18.4% increase in regeneration (P < 0.001). In the subgroup of recipients without intraoperative platelet transfusion, mean platelet count measured during the intraoperative reperfusion phase was positively associated with graft regeneration (P = 0.033).
CONCLUSIONS:Graft regeneration after LDLT increased in relation to a graded increase in the amount of transfused platelets and higher postreperfusion platelet counts during surgery. These results offer additional evidence regarding the important role of platelets in initiating liver regeneration and, furthermore, the indications for and the benefits vs risks of platelet transfusion during LDLT.
This study sought to evaluate the association between newly-developed significant hypercholesterolemia within one year following living donor liver transplantation (LDLT) and long term outcomes in ...light of cardiovascular events and graft failure. From October 2003 to July 2017, 877 LDLT recipients were stratified according to development of significant hypercholesterolemia within one year following LDLT. The primary outcome was occurrence of a major adverse cardiac event (MACE), defined as a composite of cardiac death, myocardial infarction, and coronary revascularization after LDLT. The incidence of graft failure, defined as all-cause death or retransplantation, was also compared. A total of 113 (12.9%) recipients developed significant hypercholesterolemia within one year. The differences in incidences of cardiac related events and graft related events began emerging significantly higher in the hypercholesterolemia group after 24 months and 60 months since the LDLT, respectively. After adjustment using the inverse probability of weighting, the hazard ratio (HR) for MACE was 2.77 (95% confidence interval (CI) 1.16-6.61; p = 0.02), while that for graft failure was 3.76 (95% CI 1.97-7.17, p < 0.001). A significant hypercholesterolemia after LDLT may be associated with cardiac and graft-related outcome; therefore, a further study and close monitoring of cholesterol level after LDLT is needed.
Greater graft-failure-risk of female-to-male liver transplantation (LT) is thought to be due to acute decrease in hepatic-estrogen-signaling. Our previous research found evidence that female ...hepatic-estrogen-signaling decreases after 40 years or with macrosteatosis. Thus, we hypothesized that inferiority of female-to-male LT changes according to donor-age and macrosteatosis. We stratified 780 recipients of grafts from living-donors into four subgroups by donor-age and macrosteatosis and compared graft-failure-risk between female-to-male LT and other LTs within each subgroup using Cox model. In recipients with ≤ 40 years non-macrosteatotic donors, graft-failure-risk was significantly greater in female-to-male LT than others (HR 2.03 1.18-3.49, P = 0.011). Within the subgroup of recipients without hepatocellular carcinoma, the inferiority of female-to-male LT became greater (HR 4.75 2.02-11.21, P < 0.001). Despite good graft quality, 1y-graft-failure-probability was 37.9% (23.1%-57.9%) in female-to-male LT within this subgroup while such exceptionally high probability was not shown in any other subgroups even with worse graft quality. When donor was > 40 years or macrosteatotic, graft-failure-risk was not significantly different between female-to-male LT and others (P > 0.60). These results were in agreement with the estrogen receptor immunohistochemistry evaluation of donor liver. In conclusion, we found that the inferiority of female-to-male LT was only found when donor was ≤ 40 years and non-macrosteatotic. Abrogation of the inferiority when donor was > 40 years or macrosteatotic suggests the presence of dominant contributors for post-transplant graft-failure other than graft quality/quantity and supports the role of hepatic-estrogen-signaling mismatch on graft-failure after female-to-male LT.
Osteoarthritis (OA) is a prevalent degenerative disease, which involves progressive and irreversible destruction of cartilage matrix. Despite efforts to reconstruct cartilage matrix in osteoarthritic ...joints, it has been a difficult task as adult cartilage exhibits marginal repair capacity. Here we report the identification of tankyrase as a regulator of the cartilage anabolism axis based on systems-level factor analysis of mouse reference populations. Tankyrase inhibition drives the expression of a cartilage-signature matrisome and elicits a transcriptomic pattern that is inversely correlated with OA progression. Furthermore, tankyrase inhibitors ameliorate surgically induced OA in mice, and stem cell transplantation coupled with tankyrase knockdown results in superior regeneration of cartilage lesions. Mechanistically, the pro-regenerative features of tankyrase inhibition are mainly triggered by uncoupling SOX9 from a poly(ADP-ribosyl)ation (PARylation)-dependent protein degradation pathway. Our findings provide insights into the development of future OA therapies aimed at reconstruction of articular cartilage.
Transfusion-associated graft-versus-host disease (TA-GvHD) is caused by leukocytes, specifically T cells within a transfused blood product. Currently, the prevention of transfusion-associated ...graft-versus-host disease is performed by irradiation of blood products. With a sufficient reduction of leukocytes, the risk for TA-GvHD can be decreased. With consistent advances in current state-of-the-art blood filters, we herein propose that double filtration can sufficiently reduce leukocytes to reduce the risk for TA-GvHD.
Thirty RBC concentrates were filtered with leukocyte filters, followed by storage at 1-6 oC for 72 hours, and then a second filtration was performed. Residual leukocytes in the double-filtered RBC units (n = 30) were assessed with flow cytometric methods, and an additional assay with isolated peripheral blood mononuclear cells (PBMCs) (n = 6) was done by both flow cytometric methods and an automated hematology analyzer. Quality of the RBCs after filtration was evaluated by hematological and biochemical tests. In vitro T cell expansion was performed using anti-CD3/CD28-coated Dynabeads or anti-CD3 (OKT3). In vivo experiment for GvHD was performed by using NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice.
Double-filtered blood products showed residual leukocyte levels below detection limits, which calculated to be below 1200-2500 cells per blood unit. In vitro expansion rate of T cells showed that 6x103 and 1x103 cell-seeded specimens showed 60.8±10.6 fold and 10.2±9.7-fold expansion, respectively. Cell expansion was not sufficiently observed in wells planted with 1x102 or 10 cells. In vivo experiments showed that mice injected with 1x105 or more cells cause fatal GvHD. GvHD induced inflammation was observed in mice injected with 1x104 or more cells. No evidence of GvHD was found in mice injected with 103 cells.
Our study suggests that additional removal of contaminating lymphocytes by a second leukodepletion step may further reduce the risk for TA-GvHD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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