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Investigative and Clinical Urology Sep 2020This study aimed to determine the effectiveness and safety of partial nephrectomy (PN) without ischemia compared with PN with warm ischemia for reducing the... (Comparative Study)
Comparative Study Meta-Analysis
PURPOSE
This study aimed to determine the effectiveness and safety of partial nephrectomy (PN) without ischemia compared with PN with warm ischemia for reducing the deterioration in renal function in patients with cT1 renal tumors.
MATERIALS AND METHODS
We conducted a systematic review that included patients over 18 years of age who underwent PN with or without warm ischemia for cT1 renal tumors. The primary outcome was impaired renal function. A search strategy was performed in MEDLINE, EMBASE, LILACS, CENTRAL, the article reference lists, and the unpublished literature to reach saturation of the information. We assessed the risk of bias with the methodological index for nonrandomized studies (MINORS) tool, and we performed a meta-analysis according to the type of variable.
RESULTS
We found a total of 5,682 articles, of which 14 met the inclusion criteria. Seven studies evaluated renal function, identifying a difference in means (MD) of 3.50 (95% confidence interval [CI], 1.16 to 5.83), favoring no ischemia. We did not find any significant differences regarding intraoperative bleeding or operative time (MD, 55 mL; 95% CI, -33.16 to 144.08; and MD, 1.87; 95% CI, -20.47 to 24.21; respectively).
CONCLUSIONS
In this study, PN without ischemia showed a decrease in deterioration of the estimated glomerular filtration rate compared with warm ischemia.
Topics: Humans; Kidney Neoplasms; Neoplasm Staging; Nephrectomy; Treatment Outcome; Warm Ischemia
PubMed: 32869563
DOI: 10.4111/icu.20190313 -
Kidney International Mar 2016Warm ischemia time is a potentially modifiable insult to transplanted kidneys, but little is known about its effect on long-term outcomes. Here we conducted a study of... (Comparative Study)
Comparative Study
Warm ischemia time is a potentially modifiable insult to transplanted kidneys, but little is known about its effect on long-term outcomes. Here we conducted a study of United States kidney transplant recipients (years 2000-2013) to determine the association between warm ischemia time (the time from organ removal from cold storage to reperfusion with warm blood) and death/graft failure. Times under 10 minutes were potentially attributed to coding error. Therefore, the 10-to-under-20-minute interval was chosen as the reference group. The primary outcome was mortality and graft failure (return to chronic dialysis or preemptive retransplantation) adjusted for recipient, donor, immunologic, and surgical factors. The study included 131,677 patients with 35,901 events. Relative to the reference patients, times of 10 to under 20, 20 to under 30, 30 to under 40, 40 to under 50, 50 to under 60, and 60 and more minutes were associated with hazard ratios of 1.07 (95% confidence interval, 0.99-1.15), 1.13 (1.06-1.22), 1.17 (1.09-1.26), 1.20 (1.12-1.30), and 1.23 (1.15-1.33) for the composite event, respectively. Association between prolonged warm ischemia time and death/graft failure persisted after stratification by donor type (living vs. deceased donor) and delayed graft function status. Thus, warm ischemia time is associated with adverse long-term patient and graft survival after kidney transplantation. Identifying strategies to reduce warm ischemia time is an important consideration for future study.
Topics: Adult; Delayed Graft Function; Female; Graft Survival; Humans; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Registries; Renal Dialysis; Reoperation; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; United States; Warm Ischemia; Young Adult
PubMed: 26880458
DOI: 10.1016/j.kint.2015.09.002 -
Frontiers in Immunology 2020Liver allograft rejection remains a significant cause of morbidity and graft failure in liver transplant recipients. Rejection is caused by the recognition of non-self... (Review)
Review
Liver allograft rejection remains a significant cause of morbidity and graft failure in liver transplant recipients. Rejection is caused by the recognition of non-self donor alloantigens by recipient T-cells. Antigen recognition results in proliferation and activation of T-cells in lymphoid tissue before migration to the allograft. Activated T-cells have a variety of effector mechanisms including direct T-cell mediated damage to bile ducts, endothelium and hepatocytes and indirect effects through cytokine production and recruitment of tissue-destructive inflammatory cells. These effects explain the histological appearances of typical acute T-cell mediated rejection. In addition, donor specific antibodies, most typically against HLA antigens, may give rise to antibody-mediated rejection causing damage to the allograft primarily through endothelial injury. However, as an immune-privileged site there are several mechanisms in the liver capable of overcoming rejection and promoting tolerance to the graft, particularly in the context of recruitment of regulatory T-cells and promotors of an immunosuppressive environment. Indeed, around 20% of transplant recipients can be successfully weaned from immunosuppression. Hence, the host immunological response to the liver allograft is best regarded as a balance between rejection-promoting and tolerance-promoting factors. Understanding this balance provides insight into potential mechanisms for novel anti-rejection therapies.
Topics: Allografts; Antigen Presentation; Cold Ischemia; Cytokines; Cytotoxicity, Immunologic; Graft Rejection; HLA Antigens; Humans; Immune Tolerance; Immunologic Memory; Immunosuppressive Agents; Ischemia; Isoantibodies; Isoantigens; Leukocytes; Liver; Liver Transplantation; Lymphocyte Activation; Lymphocyte Subsets; Macrophages; Reperfusion Injury; Stromal Cells; T-Lymphocytes, Regulatory; Warm Ischemia
PubMed: 32983177
DOI: 10.3389/fimmu.2020.02155 -
Frontiers in Molecular Biosciences 2022Ischemic acute kidney injury (AKI) has always been a hot and difficult research topic in the field of renal diseases. This study aims to illustrate the safe warm...
Ischemic acute kidney injury (AKI) has always been a hot and difficult research topic in the field of renal diseases. This study aims to illustrate the safe warm ischemia time of kidney and the molecular network characteristics and pathological features of mild to severe ischemia reperfusion kidney injury. We established varying degrees of renal injury due to different ischemia time (0 min, 16 min, 18 min, 20 min, 22 min, 24 min, 26 min, 28 min, and 30 min) on unilateral (left kidney) ischemia-reperfusion injury and contralateral (right kidney) resection (uIRIx) mouse model. Mice were sacrificed 24 h after uIRIx, blood samples were harvested to detect serum creatinine (Scr), and kidney tissue samples were harvested to perform Periodic Acid-Schiff (PAS) staining and RNA-Seq. Differentially expressed genes (DEGs) were identificated, time-dependent gene expression patterns and functional enrichment analysis were further performed. Finally, qPCR was performed to validated RNA-Seq results. Our results indicated that there was no absolute safe renal warm ischemia time, and every minute of ischemia increases kidney damage. Warm ischemia 26min or above in mice makes severe kidney injury, renal pathology and SCr were both significantly changed. Warm ischemia between 18 and 26 min makes mild kidney injury, with changes in pathology and renal molecular expression, while SCr did not change. No obvious pathological changes but significant differences in molecular expression were found less than 16min warm ischemia. There are two key time intervals in the process of renal ischemia injury, 0 min-16 min (short-term) and 26 min-28 min (long-term). Gene expression of immune-related pathways were most significantly down-regulated in short-term ischemia, while metabolism-related pathways were the mainly enriched pathway in long-term ischemia. Taken together, this study provides novel insights into safe renal artery occlusion time in partial nephrectomy, and is of great value for elucidating molecular network characteristics and pathological features of mild to severe ischemia reperfusion kidney injury, and key genes related to metabolism and immune found in this study also provide potential diagnostic and therapeutic biomarkers for AKI.
PubMed: 36465563
DOI: 10.3389/fmolb.2022.1006917 -
International Journal of Clinical and... 2019This study was conducted to investigate the effect of warm ischemia duration on hepatocyte mitochondrial damage after liver transplantation, and confirm the role of...
This study was conducted to investigate the effect of warm ischemia duration on hepatocyte mitochondrial damage after liver transplantation, and confirm the role of CaMKIIγ in this process. Rat donation after cardiac death (DCD) liver transplantation model was established by exposing donor liver to 0 (W group), 15 (W group), and 30 (W group) min warm ischemia. Some rats in W group were transfected with CaMKIIγ and CaMKIIγ-shRNA lentivirus. On day 1, 3, and 7 post-transplantation, a series of experiments, including HE staining, TEM observation, ALT and AST measurement, flow cytometry analysis, qRT-PCR, and Western blotting were performed to evaluate the extent of hepatic and mitochondria damage. Within 7 days post-transplantation, prolonged ischemia led to an obvious deterioration of hepatic and mitochondria damage, presenting with a marked increase of apoptotic hepatocytes, ALT and AST levels, cells with low MMP, and AIF and Cyt C expression. CaMKIIγ overexpression caused the significant ultrastructural damage of hepatic cells, increase of cells with low MMP, enhancement of AIF and Cyt C expression, and augmented Ca/CaM/CaMKIIγ, while blocking CaMKIIγ showed an opposite result. In conclusion, ischemia duration is proportional to the extent of hepatic mitochondria damage, and CaMKIIγ plays a negative regulatory role in this process by regulating the Ca/CaM/CaMKII signaling pathway.
PubMed: 31933737
DOI: No ID Found -
Canadian Journal of Gastroenterology &... 2019Decreased organ function following liver resection is a major clinical issue. The practical method of ischemic postconditioning (IPostC) has been studied in heart...
BACKGROUND
Decreased organ function following liver resection is a major clinical issue. The practical method of ischemic postconditioning (IPostC) has been studied in heart diseases, but no data exist regarding fibrotic livers.
AIMS
We aimed to determine whether IPostC could protect healthy, fibrotic, and cirrhotic livers from ischemia reperfusion injury (IRI).
METHODS
Fibrosis was induced in male SD rats using bile duct ligation (BDL, 4 weeks), and cirrhosis was induced using thioacetamide (TAA, 18 weeks). Fibrosis and cirrhosis were histologically confirmed using HE and EvG staining. For healthy, fibrotic, and cirrhotic livers, isolated liver perfusion with 90 min of warm ischemia was performed in three groups (each with n=8): control, IPostC 8x20 sec, and IPostC 4x60 sec. additionally, healthy livers were investigated during a follow-up study. Lactate dehydrogenase (LDH) and thromboxane B (TXB) in the perfusate, as well as bile flow (healthy/TAA) and portal perfusion pressure, were measured.
RESULTS
LDH and TXB were reduced, and bile flow was increased by IPostC, mainly in total and in the late phase of reperfusion. The follow-up study showed that the perfusate derived from a postconditioned group had much less damaging potential than perfusate derived from the nonpostconditioned group.
CONCLUSION
IPostC following warm ischemia protects healthy, fibrotic, and cirrhotic livers against IRI. Reduced efflux of TXB is one possible mechanism for this effect of IPostC and increases sinusoidal microcirculation. These findings may help to improve organ function and recovery of patients after liver resection.
Topics: Animals; Disease Models, Animal; Ischemic Postconditioning; Liver; Liver Cirrhosis; Male; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Warm Ischemia
PubMed: 31281804
DOI: 10.1155/2019/5683479 -
American Journal of Translational... 2014To quantitatively and visually characterize changes in phosphorylated biomarker expression in head and neck squamous cell carcinoma specimens from excision through 90...
OBJECTIVES
To quantitatively and visually characterize changes in phosphorylated biomarker expression in head and neck squamous cell carcinoma specimens from excision through 90 minutes of warm ischemia.
MATERIALS AND METHODS
Tissue biospecimens were procured prospectively. Head and neck squamous cell carcinoma specimens from 5 patients were subdivided into three parts upon excision, exposed to warm ischemia of 15, 30, or 90 minutes, and routinely biobanked. Relative change in biomarker expression of p-Akt, p-ERK, and p-Stat3 was measured by immunoblot densitometry. Immunofluorescent stains were performed to visually supplement the quantitative analysis.
RESULTS
From 15 to 30 minutes of ex vivo ischemia, there was a significant decrease in p-Akt (p = 0.045) as the mean intensity fell by 44.9%. This decrease in p-Akt remained significant at the 90 minute time point (p = 0.015). From 15 to 30 minutes of ischemia, there was a trend toward a decline in p-ERK, which became significant by 90 minutes of ex vivo warm ischemia (p = 0.008). These changes were supported by qualitative differences in p-ERK fluorescence at 0 and 90 minutes warm ischemia.
CONCLUSION
Some phosphorylated biomarkers of HNSCC remain highly dynamic during the period of ex vivo warm ischemia after surgical excision but before biobanking. These findings have critical implications for studies that attempt to correlate protein phosphorylation with clinical outcome. We conclude that ex vivo warm ischemia time is a major determinant of tissue quality that may explain inconsistent results from biomarker research in head and neck squamous cell carcinoma.
PubMed: 25360219
DOI: No ID Found -
Sulforaphane Is Protective against Warm Ischemia/Reperfusion Injury and Partial Hepatectomy in Rats.International Journal of Molecular... Jan 2024Sulforaphane (SFN) has various beneficial effects on organ metabolism. However, whether SFN affects inflammatory mediators induced by warm hepatic ischemia/reperfusion...
Sulforaphane (SFN) has various beneficial effects on organ metabolism. However, whether SFN affects inflammatory mediators induced by warm hepatic ischemia/reperfusion injury (HIRI) is unclear. To investigate the hepatoprotective effects of SFN using an in vivo model of HIRI and partial hepatectomy (HIRI + PH), rats were subjected to 15 min of hepatic ischemia with blood inflow occlusion, followed by 70% hepatectomy and release of the inflow occlusion. SFN (5 mg/kg) or saline was randomly injected intraperitoneally 1 and 24 h before ischemia. Alternatively, ischemia was prolonged for 30 min to evaluate the effect on mortality. The influence of SFN on the associated signaling pathways was analyzed using the interleukin 1β (IL-1β)-treated primary cultured rat hepatocytes. In the HIRI + PH-treated rats, SFN reduced serum liver enzyme activities and the frequency of pathological liver injury, such as apoptosis and neutrophil infiltration. SFN suppressed tumor necrosis factor-alpha (TNF-α) mRNA expression and inhibited nuclear factor-kappa B (NF-κB) activation by HIRI + PH. Mortality was significantly reduced by SFN. In IL-1β-treated hepatocytes, SFN suppressed the expression of inflammatory cytokines and NF-κB activation. Taken together, SFN may have hepatoprotective effects in HIRI + PH in part by inhibiting the induction of inflammatory mediators, such as TNF-α, via the suppression of NF-κB in hepatocytes.
Topics: Animals; Rats; Hepatectomy; NF-kappa B; Tumor Necrosis Factor-alpha; Warm Ischemia; Reperfusion Injury; Inflammation Mediators; Interleukin-1beta; Ischemia; Sulfoxides; Isothiocyanates
PubMed: 38203749
DOI: 10.3390/ijms25010579 -
Mediators of Inflammation 2017Liver ischemia and reperfusion (I/R) induce local and distant tissue injuries, contributing to morbidity and mortality in a wider range of pathologies. This is...
Liver ischemia and reperfusion (I/R) induce local and distant tissue injuries, contributing to morbidity and mortality in a wider range of pathologies. This is especially seen under uncontrolled aseptic inflammatory conditions, leading to injury of remote organs, such as lung injury, and even failure. Saquinavir (SQV) is a kind of HIV protease inhibitor that possesses an anti-inflammatory property. In this study, we investigated whether SQV suppresses Toll-like receptor 4- (TLR4-) dependent signaling pathways of high-mobility group box 1 (HMGB1) and P38/JNK, conferring protection against murine liver I/R-induced lung injury. To investigate our hypothesis, C57BL/6 mice and TLR4 knockout mice (TLR4) were used to perform the study. SQV administration markedly attenuated remote lung tissue injury after 1-hour ischemia and 6-hour reperfusion of the liver. To our expectation, SQV attenuated I/R-induced lung edema, hyperpermeability, and pathological injury. The beneficial effects of SQV were associated with decreased levels of circulating and lung tissue inflammatory cytokines, such as IL-6, IL-1, TNF-, and iNOS. The protective effect of SQV was also associated with decreased lung tissue expression of HMGB1, TLR-4, and p-P38/JNK, but not p-ERK in wild-type liver I/R mice. Overall, this study demonstrated a new role of SQV, facilitating negative regulation of HMGB1- and P38/JNK-mediated TLR-4-dependent signaling pathways, conferring protection against liver I/R-induced lung injury.
Topics: Animals; Cytokines; HMGB1 Protein; JNK Mitogen-Activated Protein Kinases; Liver; Lung Injury; Male; Mice; Mice, Inbred C57BL; Reperfusion Injury; Saquinavir; Signal Transduction; Toll-Like Receptor 4; Warm Ischemia; p38 Mitogen-Activated Protein Kinases
PubMed: 29440779
DOI: 10.1155/2017/7083528 -
Transplantation Direct Jun 2022The expansion of donation after circulatory determination of death (DCDD) programs and unmet demands for kidney transplantation indicate that there is a need to improve...
BACKGROUND
The expansion of donation after circulatory determination of death (DCDD) programs and unmet demands for kidney transplantation indicate that there is a need to improve the efficiency and utilization of these organs.
METHODS
We studied all DCDD donors retrieved for kidney transplantation in Australia between 2014 and 2019 and determined the factors associated with nonutilization using least absolute shrinkage and selection operator and random forest models. Self-organizing maps were used to group these donors into clusters with similar characteristics and features associated with nonutilization were defined.
RESULTS
Of the 762 DCDD donors, 116 (15%) were not utilized for kidney transplantation. Of the 9 clusters derived from self-organizing map, 2 had the highest proportions of nonutilized kidneys. Factors for nonutilization (adjusted odds ratio [95% confidence interval], per SD increase) were duration from withdrawal of cardiorespiratory support till death (1.38 [1.16-1.64]), admission and terminal serum creatinine (1.43 [1.13-1.85]) and (1.41 [1.16-1.73]). Donor kidney function and duration of warm ischemia were the main factors for clinical decisions taken not to use kidneys from DCDD donors.
CONCLUSIONS
Donor terminal kidney function and the duration of warm ischemia are the key factors for nonutilization of DCDD kidneys. Strategies to reduce the duration of warm ischemia and improve post-transplant recipient kidney function may reduce rates of nonutilization.
PubMed: 35721459
DOI: 10.1097/TXD.0000000000001331