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Heliyon Mar 2024normothermic machine perfusion (NMP) preserves donor organs and permits real-time assessment of allograft health, but the most effective indicators of graft viability...
normothermic machine perfusion (NMP) preserves donor organs and permits real-time assessment of allograft health, but the most effective indicators of graft viability are uncertain. Mitochondrial DNA (mtDNA), released consequent to traumatic cell injury and death, including the ischemia-reperfusion injury inherent in transplantation, may meet the need for a biomarker in this context. We describe a real time PCR-based approach to assess cell-free mtDNA during NMP as a universal biomarker of allograft quality. Measured in the perfusate fluid of 29 livers, the quantity of mtDNA correlated with metrics of donor liver health including International Normalized Ratio (INR), lactate, and warm ischemia time, and inversely correlated with inferior vena cava (IVC) flow during perfusion. Our findings endorse mtDNA as a simple and rapidly measured feature that can inform donor liver health, opening the possibility to better assess livers acquired from extended criteria donors to improve organ supply.
PubMed: 38463874
DOI: 10.1016/j.heliyon.2024.e27122 -
Annals of Gastroenterological Surgery Mar 2024The use of extended criteria donors is a routine practice that sometimes involves extracorporeal membrane oxygenation (ECMO) in donations after cardiac death or brain...
AIMS
The use of extended criteria donors is a routine practice that sometimes involves extracorporeal membrane oxygenation (ECMO) in donations after cardiac death or brain death.
METHODS
We performed a retrospective study in a single center from January 2006 to December 2019. The study included 90 deceased donor liver transplants. The patients were divided into three groups: the donation after brain death (DBD) group ( = 58, 64.4%), the DBD with ECMO group ( = 11, 12.2%) and the donation after cardiac death (DCD) with ECMO group ( = 21, 23.3%).
RESULTS
There were no significant differences between the DBD with ECMO group and the DBD group. When comparing the DCD with ECMO group and the DBD group, there were statistically significant differences for total warm ischemia time ( < 0.001), total cold ischemia time ( = 0.023), and split liver transplantation ( < 0.001), and there was significantly poor recovery in regard to total bilirubin level ( = 0.027) for the DCD with ECMO group by repeated measures ANOVA. The 5-year survival rates of the DBD, DBD with ECMO, and DCD with ECMO groups were 78.1%, 90.9%, and 75.6%, respectively. The survival rate was not significantly different when comparing the DBD group to either the DBD with ECMO group ( = 0.435) or the DCD with ECMO group ( = 0.310).
CONCLUSIONS
Using ECMO in donations after cardiac death or brain death is a good technology, and it contributed to 35.6% of the liver graft pool.
PubMed: 38455485
DOI: 10.1002/ags3.12749 -
Journal of Translational Medicine Mar 2024Cellular stress associated with static-cold storage (SCS) and warm reperfusion of donor lungs can contribute to ischemia-reperfusion (IR) injury during transplantation....
BACKGROUND
Cellular stress associated with static-cold storage (SCS) and warm reperfusion of donor lungs can contribute to ischemia-reperfusion (IR) injury during transplantation. Adding cytoprotective agents to the preservation solution may be conducive to reducing graft deterioration and improving post-transplant outcomes.
METHODS
SCS and warm reperfusion were simulated in human lung epithelial cells (BEAS-2B) by exposing cells to low potassium dextran glucose solution at 4 °C for different periods and then switching back to serum-containing culture medium at 37 °C. Transcriptomic analysis was used to explore potential cytoprotective agents. Based on its results, cell viability, caspase activity, cell morphology, mitochondrial function, and inflammatory gene expression were examined under simulated IR conditions with or without thyroid hormones (THs).
RESULTS
After 18 h SCS followed by 2 h warm reperfusion, genes related to inflammation and cell death were upregulated, and genes related to protein synthesis and metabolism were downregulated in BEAS-2B cells, which closely mirrored gene profiles found in thyroid glands of mice with congenital hypothyroidism. The addition of THs (T3 or T4) to the preservation solution increases cell viability, inhibits activation of caspase 3, 8 and 9, preserves cell morphology, enhances mitochondrial membrane potential, reduces mitochondrial superoxide production, and suppresses inflammatory gene expression.
CONCLUSION
Adding THs to lung preservation solutions may protect lung cells during SCS by promoting mitochondrial function, reducing apoptosis, and inhibiting pro-inflammatory pathways. Further in vivo testing is warranted to determine the potential clinical application of adding THs as therapeutics in lung preservation solutions.
Topics: Humans; Mice; Animals; Organ Preservation; Lung; Reperfusion Injury; Reperfusion; Epithelial Cells; Thyroid Hormones
PubMed: 38429788
DOI: 10.1186/s12967-024-05024-x -
Immunity, Inflammation and Disease Feb 2024Ischemia/reperfusion injury (IRI) is generally unavoidable following liver transplantation. Here, we investigated the role of protein phosphatase, Mg /Mn dependent 1G...
BACKGROUND
Ischemia/reperfusion injury (IRI) is generally unavoidable following liver transplantation. Here, we investigated the role of protein phosphatase, Mg /Mn dependent 1G (PPM1G) in hepatic IRI.
METHODS
Hepatic IRI was mimicked by employing a hypoxia/reperfusion (H/R) model in RAW 264.7 cells and a 70% warm ischemia model in C57BL/6 mice, respectively. In vitro, expression changes of tumor necrosis factor-α and interleukin were detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blot analysis, and enzyme-linked immunosorbent assay. The protein expressions of PPM1G and the stimulator of interferon genes (STING) pathway components were analyzed by western blot. Interaction between PPM1G and STING was verified by coimmunoprecipitation (CO-IP). Immunofluorescence was applied for detection of p-IRF3. Flow cytometry, qRT-PCR and western blot were utilized to analyze markers of macrophage polarization. In vivo, histological analyses of mice liver were carried out by TUNEL and H&E staining. Changes in serum aminotransferases were also detected.
RESULTS
Following H/R intervention, a steady decline in PPM1G along with an increase in inflammatory cytokines in vitro was observed. Addition of plasmid with PPM1G sequence limited the release of inflammatory cytokines and downregulated phosphorylation of STING. CO-IP validated the interaction between PPM1G and STING. Furthermore, inhibition of PPM1G with lentivirus enhanced phosphorylation of STING and its downstream components; meanwhile, p65, p38, and Jnk were also surged to phosphorylation. Expression of INOS and CD86 was surged, while CD206, Arg-1, and IL-10 were inhibited. In vivo, PPM1G inhibition further promoted liver damage, hepatocyte apoptosis, and transaminases release. Selective inhibition of STING with C-176 partially reversed the activation of STING pathway and inflammatory cytokines in vitro. M1 markers were also suppressed by C-176. In vivo, C-176 rescued liver damage and transaminase release caused by PPM1G inhibition.
CONCLUSION
PPM1G suppresses hepatic IRI and macrophage M1 phenotype by repressing STING-mediated inflammatory pathways.
Topics: Animals; Mice; Cytokines; Ischemia; Liver Diseases; Macrophages; Mice, Inbred C57BL; Reperfusion Injury; Protein Phosphatase 2C
PubMed: 38372470
DOI: 10.1002/iid3.1189 -
Journal of Robotic Surgery Feb 2024Robotic nephron-sparing surgery is traditionally performed via a transperitoneal (TP) approach. However, the retroperitoneal (RP) approach has gained popularity,...
Robotic nephron-sparing surgery is traditionally performed via a transperitoneal (TP) approach. However, the retroperitoneal (RP) approach has gained popularity, particularly for posterolateral renal masses. The RP approach is associated with shorter operative time, less blood loss, and shorter length of stay, while preserving oncologic outcomes in selected masses. Here, we aim to assess the feasibility of the RP approach in excising anterior renal masses. Patients ≥ 18 years of age who underwent robotic nephron-sparing surgery for anterior renal masses were retrospectively identified (2008-2022). Baseline demographics, tumor characteristics, and perioperative data were collected and characterized based on TP vs RP approaches. Wilcoxon rank sum test and Pearson's Chi-squared test were used to compare continuous and categorical variables, respectively. Two hundred and sixteen patients were included-178 (82.4%) underwent TP approach and 38 (17.6%) underwent RP approach. Baseline demographics, preoperative tumor size, and renal nephrometry scores were similar. The RP approach was associated with shorter operative (150 vs 203 min, p < 0.001) and warm ischemia time (12 vs 21 min, p < 0.001), and less blood loss (20 vs 100 cc, p = 0.002) (Table 1). The RP approach was associated with shorter length of stay (1 vs 2 days, p < 0.001) and less total complications (5.3% vs 19.1%, p = 0.038). Major complication (Clavien-Dindo Grade > 3) rates were similar. There was no difference in positive surgical margin rates or pathologic characteristics. Robotic RP approach for nephron-sparing surgery is feasible for eligible anterior tumors and is associated with favorable perioperative outcomes with preserved negative surgical margin rates. Table 1 Patient baseline demographics Overall Transperitoneal Retroperitoneal p value Median/N IQR/% Median/N IQR/% Median/N IQR/% N 216 178 82.4% 38 17.6% Age (years) 60.5 (52.1-67.7) 60.4 (52.8-67.7) 61.6 (49.1-69.2) 0.393 Sex Male 126 58.3% 100 56.2% 26 68.4% Female 90 41.7% 78 43.8% 12 31.6% 0.165 Race White 162 75.0% 137 77.0% 25 65.8% Asian 4 1.9% 2 1.1% 2 5.3% Black 21 9.7% 18 10.1% 3 7.9% Hispanic 26 12.0% 18 10.1% 8 21.1% Other 2 0.9% 2 1.1% 0 0.0% 0.197 Body mass index (kg/m) < 25 32 14.8% 25 14.0% 7 18.4% 25-30 68 31.5% 55 30.9% 13 34.2% 30-35 60 27.8% 50 28.1% 10 26.3% 35 + 56 25.9% 48 27.0% 8 21.1% 0.808 Prior abdominal surgery Yes 118 54.6% 104 58.4% 14 36.8% No 98 45.4% 74 41.6% 24 63.2% 0.015 Prior kidney surgery Yes 10 4.6% 9 5.1% 1 2.6% No 206 95.4% 169 94.9% 37 97.4% 0.518 Chronic kidney disease stage ≥ 3 Yes 45 20.8% 38 21.3% 7 18.4% No 171 79.2% 140 78.7% 31 81.6% 0.687 Charlson comorbidity index 0 138 63.9% 116 65.2% 22 57.9% 1 46 21.3% 38 21.4% 8 21.1% 2 19 8.8% 13 7.3% 6 15.8% ≥ 3 13 6.0% 11 6.2% 2 5.3% 0.412 Tumor size (cm) 2.7 (2-3.6) 2.8 (2-3.5) 2.55 (2-3.7) 0.796 Tumor laterality Left 100 46.3% 78 43.8% 22 57.9% Right 116 53.7% 100 56.2% 16 42.1% 0.114 Clinical T stage cT1a 186 86.1% 152 85.4% 34 89.5% cT1b 30 13.9% 26 14.6% 4 10.5% 0.509 RENAL Nephrometry score Low (4 to 6) 94 43.5% 76 42.7% 18 47.4% Intermediate (7 to 9) 112 51.9% 94 52.8% 18 47.4% High (≥ 10) 19 4.6% 8 4.5% 2 5.3% 0.829 TE tumor enucleation, SPN standard margin partial nephrectomy, IQR interquartile range.
Topics: Humans; Female; Male; Retrospective Studies; Robotic Surgical Procedures; Nephrectomy; Neoplasms; Nephrons
PubMed: 38353825
DOI: 10.1007/s11701-023-01798-2 -
Scientific Reports Feb 2024Liver failure secondary to metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most common cause for liver transplantation in many parts of...
Liver failure secondary to metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most common cause for liver transplantation in many parts of the world. Moreover, the prevalence of MASLD not only increases the demand for liver transplantation, but also limits the supply of suitable donor organs because steatosis predisposes grafts to ischemia-reperfusion injury (IRI). There are currently no pharmacological interventions to limit hepatic IRI because the mechanisms by which steatosis leads to increased injury are unclear. To identify potential novel mediators of IRI, we used liquid chromatography and mass spectrometry to assess temporal changes in the hepatic lipidome in steatotic and non-steatotic livers after warm IRI in mice. Our untargeted analyses revealed distinct differences between the steatotic and non-steatotic response to IRI and highlighted dynamic changes in lipid composition with marked changes in glycerophospholipids. These findings enhance our knowledge of the lipidomic changes that occur following IRI and provide a foundation for future mechanistic studies. A better understanding of the mechanisms underlying such changes will lead to novel therapeutic strategies to combat IRI.
Topics: Mice; Animals; Lipidomics; Liver; Fatty Liver; Liver Transplantation; Reperfusion Injury; Warm Ischemia
PubMed: 38351300
DOI: 10.1038/s41598-024-54122-9 -
International Journal of Surgery... May 2024This study aimed to compare the safety and effectiveness of the MP1000 surgical system with the da Vinci Si robot system in robot-assisted partial nephrectomy (RAPN)... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
This study aimed to compare the safety and effectiveness of the MP1000 surgical system with the da Vinci Si robot system in robot-assisted partial nephrectomy (RAPN) through a prospective, single-blinded, randomized controlled trial.
MATERIALS AND METHODS
A total of 62 patients who were scheduled to undergo RAPN were randomly assigned to either the da Vinci Si robot or MP1000 group. A noninferiority test was conducted with a noninferior intermediate value of 10%. The study compared installation and operation times, estimated blood loss, warm ischemia time, postoperative surgical margin, rate of conversion to open surgery, eGFR level, complications, and other safety indicators between the two groups.
RESULTS
All procedures were successfully completed without the need for conversion to open or laparoscopic surgery, and no major complications were observed during the process. The test of noninferiority was achieved. There were no significant differences in median installation time, operation time, complication rate at 3 months, rate of positive surgical margin, and eGFR level at 3 months between the groups. Additionally, no evidence of recurrence was found on imaging in both groups. No difference in National Aeronautics and Space Administration task load index results for ergonomic considerations. A limitation of this study was its small sample size.
CONCLUSIONS
The MP1000 system is a suitable platform for RAPN with safety and effectiveness compared with da Vinci Si system.
Topics: Humans; Nephrectomy; Robotic Surgical Procedures; Female; Male; Middle Aged; Prospective Studies; Aged; Kidney Neoplasms; Single-Blind Method; Operative Time; Adult; Treatment Outcome
PubMed: 38349210
DOI: 10.1097/JS9.0000000000001166 -
Journal of Clinical Medicine Jan 2024The aim of our study is to compare the perioperative, functional, and oncological outcomes of laparoscopic transperitoneal partial nephrectomy (LTPN) and laparoscopic...
The aim of our study is to compare the perioperative, functional, and oncological outcomes of laparoscopic transperitoneal partial nephrectomy (LTPN) and laparoscopic retroperitoneal partial nephrectomy (LRPN) for posterior cT1 renal tumors. We retrospectively collected data on all patients who consecutively underwent LTPN and LRPN for posterior cT1 renal tumors in three different centers from January 2015 to January 2023. Patients with a single, unilateral, cT1 renal mass, located in the posterior renal surface were included. Patients' data regarding perioperative, functional, and oncological outcomes were collected from medical records and statistically analyzed and compared. A total of 128 patients was obtained, with 53 patients in the LPTN group and 75 patients in the LRPN group. Baseline characteristics were similar. Warm ischemia time (WIT) (18.8 vs. 22.6 min, = 0.002) and immediate postoperative eGFR drop (-6.1 vs. -13.0 mL/min/1.73 m, = 0.047) were significantly lower in the LPTN group. Estimated blood loss (EBL) (100 vs. 150 mL, = 0.043) was significantly lower in the LRPN group. All other perioperative and functional outcomes and complications were similar between the groups. The positive surgical margin (PSM) rate was lower in the LRPN group, although without statistical significance (7.2% vs. 13.5%, = 0.258). Surgical success defined by Trifecta (WIT ≤ 25 min, no PSM, and no major postoperative complication) was similar between both approaches. LTPN has significantly shorter WIT and a significantly smaller drop in immediate eGFR when compared to LRPN for posterior renal tumors. On the other hand, LRPN has significantly less EBL than LTPN. LRPN demonstrated fewer PSMs than LTPN, albeit without statistical significance. In terms of overall surgical success, as defined by Trifecta, both approaches achieved similar results.
PubMed: 38337397
DOI: 10.3390/jcm13030701 -
European Urology Open Science Feb 2024Repeat partial nephrectomy (PN) is an effective treatment in improving the prognosis for patients with recurrent renal cancer after initial PN. However, salvage PN (sPN)...
Repeat partial nephrectomy (PN) is an effective treatment in improving the prognosis for patients with recurrent renal cancer after initial PN. However, salvage PN (sPN) is inevitably associated with a higher rate of complications, largely because of intraperitoneal adhesions and fibrosis. Here we describe three initial cases for which recurrent renal tumors were treated with a novel minimally invasive approach, namely Ultrasound-guided Renal Artery Balloon catheter Occluded Hybrid Partial Nephrectomy (UBo-HPN).With laparoscopic ultrasound (LUS) guiding a Fogarty catheter to occlude the arterial blood supply, dissection of the renal hilum and most of the abdominal cavity can be avoided. UBo-HPN was successfully performed in three patients. One case of postoperative fever (Clavien-Dindo grade II) occurred, with no other complications. The mean operative time was 106 min, with a mean warm ischemia time of 21 min. UBo-HPN may be considered a safe and effective alternative for sPN, with a minimally invasive surgical footprint and better surgical outcomes.
PubMed: 38333046
DOI: 10.1016/j.euros.2024.01.008 -
World Journal of Pediatric Surgery 2023Living donor liver transplantation (LDLT) remains the only curative treatment for children with end-stage liver disease; however, complications of the procedure are...
BACKGROUND
Living donor liver transplantation (LDLT) remains the only curative treatment for children with end-stage liver disease; however, complications of the procedure are associated with indications for early relaparotomy. Several risk factors associated with early relaparotomy after liver transplantation include pediatric end-stage liver disease (PELD) score, warm ischemia time (WIT), and cold ischemia time (CIT). Our study investigated the incidence and indications of early relaparotomy in postoperative pediatric LDLT recipients and compared the outcomes with patients who did not require relaparotomy.
METHODS
A retrospective cohort study of pediatric LDLT recipients from Cipto Mangunkusumo Hospital, Jakarta, Indonesia, was collected from 2010 to August 2022. Indications for early relaparotomy were investigated. Factors analyzed in the early relaparotomy group compared with the nonrelaparotomy group included intraoperative blood loss, surgery duration, CIT, WIT, and PELD score.
RESULTS
The highest indication for early relaparotomy was biliary leakage. Most patients who underwent early relaparotomy only had one incidence of relaparotomy (60%). The surgery duration in subjects with early relaparotomy was longer by a median of 3 hours compared with those without early relaparotomy (p=0.289). Intraoperative blood loss was greater in early relaparotomy subjects than in subjects without early relaparotomy (95 vs 77 mL/kg, p=0.552). Other factors, such as PELD score, CIT, and WIT, also showed no significant difference between the two groups.
CONCLUSION
Biliary leakage was the most common indication for early relaparotomy in our center. There were no preoperative or intraoperative factors that significantly influenced the incidence of early relaparotomy due to the limited sample size and the early advancement of our liver transplant center.
PubMed: 38328395
DOI: 10.1136/wjps-2022-000511