Warm Ischemia Research Articles

Creating a Risk Score for Prolonged Length of Stay Following Pediatric Lung Transplants.

Pediatric lung transplant (LT) outcomes correlate with prolonged length of stay (pLOS), yet a paucity of research exists predicting pLOS in this population. We aim to identify factors associated with pLOS following pediatric LT, and to create a risk score identifying individual patients at increased risk of pLOS. Using the OPTN database, we analyzed 733 pediatric patients who received an LT between January 2000-July 2022. We used LASSO regularization to identify factors predicting pLOS. A risk score was calculated using odds ratios for each variable in the model. LASSO was run on 51 factors and identified 13 to be included in the model. The variables with the highest negative impact on LOS were recipient ethnicity (Asian, Native American, Pacific Islanders, or Mixed Race) (OR = 3.187), recipient requiring life support (OR = 2.354), and recipient age 2-10 years old (OR = 2.203). In contrast, low cold ischemia time (OR = 0.562), time on waitlist 21-60 days (OR = 0.284), and diagnosis of primary pulmonary hypertension (OR = 0.307) had protective effects on LOS. Using the risk score, we stratified patients into three equal groups: low (mean LOS = 20.60 days), medium (mean LOS = 22.53 days), and high risk (mean LOS = 36.72 days) of pLOS. The c-statistic for the model was 0.7931 and 0.7757 for the risk score. Using this model and risk score, physicians and healthcare systems could identify patients at risk of pLOS and could intervene on preventable variables before transplantation.

HPB SO76 - Is there a difference in liver transplant outcomes between daytime vs nighttime transplants?

Abstract Background Liver transplantation (LT) is the most effective treatment for end-stage liver disease. Night-time transplantations are often scheduled to minimize cold ischemia time (CIT), but they may pose challenges due to potential fatigue and circadian rhythm disruptions among surgical teams. This study aims to investigate the effect of transplant timing on the outcomes of liver transplant patients. Method A preliminary retrospective analysis was conducted on liver transplants performed between January and May 2018. Surgeries were categorized into daytime (8:00 am–8:00 pm) and nighttime (8:00 pm–8.00 am) groups. Outcomes examined included operative time, early mortality, complications (wound, vascular, biliary, and other) occurring within 30 days post-surgery, CIT, re-transplantation, length of ITU stay and length of hospital stay. Results The nighttime group, the mean recipient age was 50.17 years (SD 10.86). Surgery duration averaged 5.67 hours (SD 1.57) with a mean CIT of 8.08 hours (SD 2.41). The average hospital stay was 14days, with 1-year and 3-year survival rates of 100% and 95.68%. Acute rejection occurred in 8.7% of patients. The daytime group, the mean recipient age was 51.83 years (SD 10.86). Surgery duration averaged 5.05 hours (SD 1.20) with a mean CIT of 7.31 hours (SD 1.97). Hospital stays averaged 12.88days, with 1-year and 3-year survival rates of 97.2% and 91.67%. Acute rejection occurred in 13.9% of patients. Conclusion The preliminary results suggest slight differences in outcomes between the two groups, but a larger cohort of patients needs to be analyzed to determine statistical significance. This study will be expanded to include 400 transplant patients for a more comprehensive analysis.

Uterus Transplantation from Deceased Donors: First Italian Experience

Background: Uterus transplantation (UTx) is currently the only available treatment for absolute uterine factor infertility. Deceased donors have recently emerged as a valid alternative to living donors for uterus transplantation, with similar results. Methods: We report the first experience in Italy of uterus transplantation from deceased donors. Three uterus transplantations from deceased donors were performed at the Organ Transplant Unit of the University Hospital of Catania, Italy, between August 2020 and January 2022. Results: Two patients underwent UTx due to Mayer–Rokitansky–Küster–Hauser syndrome, while one patient had a previous hysterectomy due to benign disease. The donors’ ages were between 25 and 43 years and the mean cold ischemia time was 18.3 h. The mean age of the recipients was 31.6 years, and the mean recipient surgery duration was 5.3 h, with a mean blood loss of 766.66 mL. Two recipients developed a post-transplant hematoma, which was treated conservatively. No uterus recipient needed a re-operation during the first 30 days after transplantation. No histological signs of acute rejection were detected at the cervical biopsies performed at 1, 3, and 6 months after transplantation. First menstruation occurred in all recipients after 39 ± 12 days after transplantation. One live birth was reported 15 months after UTx. One graft was lost three months after UTx due to graft thrombosis. Conclusions: Uterus transplantation from deceased donors is emerging as a valid alternative to living donors in order to increase the donor pool.

Abstract 4147630: Towards transplantation of hearts from donation after circulatory death - stem cell derived therapy for ameliorating donor organ damage

The use of heart transplantation (HTx), a key life-saving therapy for end-stage heart failure, is limited by the shortage of acceptable donor hearts. Although donation after circulatory death (DCD) offers a potentially promising resource for clinical transplantation, its adoption for HTx is concerned by warm ischemic damage during the death process. Mesenchymal stem cell (MSC)-derived paracrine action has been proved to mediate cardioprotection. Based on our previous study showing that MSC conditioned media (MSC CM) and MSC-exosomes (MSC Exo) confer improved donor heart preservation during cold ischemic storage, we aimed to test the effect of MSC CM and MSC Exo on ex vivo recovery of ischemia-damaged myocardium and on promoting the implanted DCD heart function using an in vivo murine heterotopic heart transplantation model. Methods: Donor hearts from adult male C57BL/6 mice with 0, 30’ or 50’ in vivo warm ischemia (WI) were divided into (n=5-7/group): 1) no WI; 2) 30’-WI; 3) 50’-WI; 4) no WI+4h cold storage at 0-4°C (no WI+CS); 5) 30’-WI+CS; 6) 50’-WI+CS; 7) 50’-WI+CS+vehicle; 8) 50’-WI+CS+MSC CM; and 9) 50’-WI+CS+MSC Exo. The CM and Exo were obtained from cultivation of human bone marrow-MSCs in serum-free media for 72h and was added into preservation solution. Donor hearts were implanted into C57BL/6 male recipients using cervical heterotopic heart transplantation. At 24h post-surgery, left ventricular (LV) function was detected in transplanted hearts. Abdominal artery pressure was measured in recipients to validate technical reproducibility of the HTx model. Mitochondrial structure was detected by electron microscopy on the fixed human LV (hDCD&hDBD). Results: WI significantly impaired LV function in transplanted DCD hearts vs. no-WI (Fig. A, B). Intriguingly, markedly improved graft function was observed in MSC CM- or Exo-treated DCD hearts vs. vehicle (Fig. C). Short and disrupted cristae in mitochondria were noticed in hDCD vs. hDBD (Fig. D). Conclusions: Our results represent the initial evidence that MSC secretome (CM&Exo) mediates ex vivo cardiac repair in DCD hearts and validate an approach on MSC derived therapy to rescue marginal DCD donor hearts and improve post-transplant graft function.

The clinical efficacy of monolayer suture combined with hem-o-lok clip in partial nephrectomy among patient with renal cell carcinoma: a quasi-experimental study

ObjectiveTo explore the clinical efficacy of monolayer suture combined with a hem-o-lok clip during partial nephrectomy among patients with renal cell carcinoma (RCC).MethodsEighty patients with RCC underwent laparoscopic partial nephrectomy from January to October 2021. They were assigned into a control group and an intervention group, each with 40 cases using random number table. The control group received double-layer sutures on the wound, while the intervention group had single-layer sutures with a hem-o-lok clip for hemostasis. The study compared operative indexes and postoperative recovery of the two groups.ResultsIntraoperative bleeding and warm ischemia time in the intervention group were significantly shorter than that in the control group. There were no significant differences in operation time, drainage volume on the first day after operation, and hospital stay between the two groups. Before operation, there were no significant differences in serum creatinine and blood urea nitrogen between the two groups. However, 24 h post-operation, both groups experienced a significant increase in these levels, with the intervention group showing lower levels than the control group. Changes in glomerular filtration rate were significantly lower in the intervention group than the control group. Complication rates were similar, with 7.5% in the research group and 10.0% in the control group.ConclusionMonolayer suture combined with a hem-o-lok clip can shorten the time of warm ischemia, reduce intraoperative bleeding and the loss of normal renal parenchyma in patients undergoing laparoscopic partial nephrectomy. More studies with larger sample size are needed to confirm the results.

The clinical application value of mixed reality in robotic laparoscopic partial nephrectomy

PurposeRobot-assisted laparoscopic partial nephrectomy (RAPN) has become a key technology in the treatment of renal tumors. Effective preoperative planning and precise intraoperative navigation are critical to a successful surgical outcome. This study aimed to evaluate the clinical application value of mixed reality (MR) in robotic nephron-sparing partial nephrectomy for patients with renal tumors of different complexity based on the R.E.N.A.L. score.Patients and methodsA retrospective analysis was conducted on 68 eligible patients with renal cancer who underwent RAPN at The Second Affiliated Hospital of Nanchang University from January 2021 to December 2023, with postoperative pathology confirmation. Patients were divided into two groups: the MR group, with 28 cases, and the traditional imaging (control) group, with 40 cases. All patients underwent mid-abdominal CT plain scans and enhancements. The MR group utilized three-dimensional reconstruction of CT data and employed 3D tablets and HoloLens glasses for preoperative discussions, surgical planning, and intraoperative guidance. Collect clinical data and metrics to assess surgical outcomes, as well as evaluate performance in areas such as preoperative discussions, doctor-patient communication, surgical planning, and intraoperative navigation.ResultsCompared to robot-assisted partial nephrectomy in the control group, the MR group experienced a reduction in operation time by approximately 30 min [(135.89 ± 23.494) min vs. (165.00 ± 34.320) min, P< 0.001)] and a decrease in ischemia time by around 2.5 min [(20.36 ± 3.956) min vs. (23.80± 6.889) min, P = 0.02)]. Within the subgroup with a R.E.N.A.L. score of less than 7 points, the MR group only showed a significant reduction in operation time [(134.55 ± 150.190) min vs. (150.19 ± 28.638) min, P = 0.045], with no notable differences in other parameters. For the subgroup with a R.E.N.A.L. score of 7 points or higher, the MR group exhibited shorter operation time [(140.83 ± 25.183) min vs. (195.77 ± 23.080) min, P< 0.001] and reduced warm ischemia time [(21.17 ± 2.714) min vs. (28.85 ± 7.570) min, P = 0.029]. Additionally, there was less estimated blood loss [(53.33 ± 5.164) min vs. (114.62 ± 80.376) min, P = 0.018]. All patients had negative resection margins, indicating equivalent therapeutic outcomes between the two groups.ConclusionIn comparison to traditional RAPN, MR technology demonstrates the ability to decrease operation time and warm ischemia time all the while maintaining equivalent curative outcomes. Additionally, it enhances preoperative discussions, doctor-patient interactions, preoperative strategizing, and intraoperative navigation, particularly excelling in complex renal tumor cases of RAPN, where its benefits are most pronounced.

Effect of warm and cold ischemia on pancreaticoduodenectomy specimen following robotic pancreaticoduodenectomy

BackgroundThe adoption of robotic pancreaticoduodenectomy (PD) has increased in recent years for the treatment of pancreatic head tumors and periampullary lesions. Some potential benefits seem to be demonstrated; however, obtaining specimens through this method can potentially compromise the diagnosis depending on the timing of the specimen retrieval, and the impact of longer perioperative time on ischemia and autolysis of the surgical specimen has not been analyzed. The aim of this study is to evaluate the histological changes associated with timing of specimen retrieval during robotic PD.MethodsA review of histopathology files was performed for all pancreatic specimens collected at our hospital from January 2022 to March 2024. Both warm ischemia time (WIT) and cold ischemia time (CIT) were collected. Histological features related to ischemic damage were evaluated in normal duodenal and pancreatic parenchyma as well as pancreatic tumor, and were graded as: absent, mild, moderate and severe. Univariate and multivariate analyses were performed to determine which variables were associated with moderate and severe ischemic changes.ResultsSixty surgical specimens were analyzed: 20 open PD, 17 robotic PD with cold ischemia, and 23 robotic PD. Median total WIT was 182 min (open PD 57 min vs. RPD 190 min vs. RPD-CI 198 min; p < 0.001). Median CIT was 760 min (740–835) in samples stored at 4ºC. Univariate analysis showed that longer intraoperative time, male gender and cold ischemia were associated with pancreatic tissue ischemic changes. In multivariate analysis, cold ischemia was the only independent factor associated with normal pancreatic tissue and tumor tissue moderate and severe ischemic changes.ConclusionsProlonged ischemia time, especially in the case of cold storage, has a strong effect on the degradation of normal and tumor tissue without affecting pathological evaluation. Operative teams should aim to optimize both the duration and efficiency of the surgical procedure, ensuring minimal ischemic time. Simultaneously, pathology departments must be equipped to process pancreatic specimens promptly, with protocols in place to minimize the time between resection and analysis.

Perfusate Biomarkers of DCD Cardiac Graft Quality Identified With Proteomics: Studies in an Isolated Rat Heart Model.

Heart transplantation with donation after circulatory death (DCD) enhances cardiac graft availability, but exposes hearts to potentially damaging conditions, such as warm ischemia. Normothermic machine perfusion (NMP), used for graft transportation, allows biomarker determination in perfusate. Using our isolated, rat heart model of DCD, we evaluated potent. Isolated, perfused adult male Wistar rat hearts (n = 5/group) underwent different warm ischemic durations to simulate DCD, followed by reperfusion to simulate NMP. Perfusate samples were collected after 10 min reperfusion, and proteins were analyzed using mass spectrometry. Cardiac recovery was evaluated after 60 min reperfusion. The relationship between perfusate proteins and cardiac recovery was investigated. Cardiac recovery decreased with increasing ischemic duration. Principal component analysis of perfusate proteins demonstrated segregation by ischemic group. Several proteins demonstrated an On-Off pattern, and correlated with key outcome measurements. Other proteins were released by all hearts and were confirmed as predictors of cardiac recovery, for example, heat shock protein 70 and valosin-containing protein (area under the curve [AUC] = 0.962-0.968, respectively; P < 0.05 for all). Additionally, proteins such as glycogen phosphorylase, muscle associated (AUC = 0.9632; P < 0.05) showed potential as novel biomarkers for evaluating cardiac graft quality, unlike lactate release after 10 min of reperfusion (AUC = 0.60). Multiple perfusate proteins, such as heat shock protein 70, valosin-containing protein, or glycogen phosphorylase, muscle associated, released during early reperfusion are promising as biomarkers for assessing graft quality during NMP. Perfusate proteins, as biomarkers, offer the possibility of both rapid immune detection and out-of-hospital implementation, and may provide valuable information about graft quality, especially when profiled with serial sampling during NMP.

Synthetic torpor confers cardioprotection against myocardial ischaemia/reperfusion injury in the rat

Abstract Introduction Torpor is a hypothermic, bradycardic, hypometabolic state enabling animals, such as mice, to survive in unfavourable environmental conditions such as cold exposure or reduced food availability. It is thought to be a cardioprotective state. There is interest in developing models that mimic aspects of torpor in clinical settings such as ischaemia-reperfusion injury. The preoptic area of the hypothalamus (POA) has emerged as a key centre for triggering torpor in the mouse. Purpose Induce a synthetic torpor-like state in a species that does not naturally enter torpor (the rat) by chemoactivation of neurons in the POA that correspond to those that induce torpor in the mouse. Test the cardioprotective effects of synthetic torpor in the Langendorff ischaemia-reperfusion preparation. Methods Designer receptors exclusively activated by designer drugs (DREADDs) were used to exogenously activate excitatory neurons in the POA of the rat hypothalamus. Viral vectors (pAAV-CaMKIIa-hM3D(Gq)-mCherry) were stereotaxically injected bilaterally into the POA under ketamine and medetomidine anaesthesia, resulting in expression of DREADDs in excitatory neurons. Control animals received a vector delivering the gene for a fluorescent protein only. DREADD receptors in transfected neurons were activated by subsequent injection of Clozapine-N-Oxide (CNO, 2mg/kg IP), which results in neuronal activation and induces synthetic torpor. Heart rate and core temperature were monitored using implanted telemeters. 2 weeks after vector injection, animals were anaesthetised using 5% isoflurane and culled by cervical dislocation. Hearts were excised and ex-vivo whole heart perfusion at 37°C was performed using the Langendorff apparatus. Hearts were subjected to 30 minutes of global warm ischaemia followed by 60 minutes of reperfusion. Hearts were stained using tetrazolium triphenyl chloride, and infarct size as a proportion of the total heart area calculated. Results Chemoactivation of rat POA neurons induced synthetic torpor characterised by bradycardia (pre: 341.0 ± 17.73bpm, post: 233.4 ± 20.47bpm, paired t (4) = 5.4791, p = .0054) and hypothermia (36.2 ±0.40°C vs 31.6 ± 0.55°C (paired t (4) = 7.9023, p = .0014). CNO had no effect on heart rate or core temperature in control animals. The mean infarct size was significantly lower in synthetic torpor (21.54 ±2.84%) compared to control hearts (29.62 ±2.59%) (unpaired t (23) = 2.1054, p = .0464). Conclusions Synthetic torpor, induced centrally in a species for which torpor is not a natural behaviour, confers striking cardioprotection in an ex-vivo ischaemia-reperfusion model. This novel approach to cardioprotection against myocardial ischaemia/reperfusion injury should be further investigated as a potential therapeutic target for use in clinical practice.

Use of fibrin sealant in vein anastomosis in renal transplantation and its effect in preventing blood loss and postoperative peri-graft collection.

This study is to assess efficacy of fibrin sealant in vein anastomosis in renal transplantation in preventing blood loss and postoperative peri-graft collection. This is a retrospective analytical case-control study of renal transplantations done in a tertiary care center in India in a 1-year period. Fibrin sealant was randomly used in vein anastomosis during the period. All the data were extracted and retrospectively analyzed. Those with fibrin sealant use were the study group and without sealant use were the control group. Primary objective was to assess effectiveness of fibrin sealant in preventing blood loss and postoperative peri-graft collection. Secondary objectives were to evaluate patients' demographic profile, hospital stay and other intraoperative and postoperative characteristics. During the study, 163 patients were enrolled, 82 study group and 81 control group. Warm ischemia, cold ischemia and operative times of study group were 2.57 ± 2.03, 44.23 ± 8.89 and 189.6 ± 51.6min, respectively, and that of control group were 2.67 ± 2.07, 42.37 ± 8.5 and 178.8 ± 54.6min, respectively. The mean intraoperative blood loss in study and control groups was 124.83 ± 110.89 and 155 ± 50.27ml, respectively, and the difference was statistically significant (p .027). The mean peri-graft collection in study group and control group were 72.33 ± 29.18ml and 134.67 ± 102.84ml, respectively, but the difference was not statistically significant (p .086). The study also demonstrated that the duration of hospital stays significantly differed between two groups (p < .043). In this study, fibrin sealant has demonstrated both safety and efficacy in effectively managing bleeding, sealing vascular anastomoses, and mitigating peri-graft collection.

Accuracy of warm ischemia time measurement using a surgical intelligence software in partial nephrectomies: A validation study

AbstractObjectivesThe objectives of this study are to compare the accuracy of warm ischemia times (WITs) derived by a surgical artificial intelligence (AI) software to those documented in surgeon operative reports during partial nephrectomy procedures and to assess the potential of this technology in evaluating postoperative renal function.Patients and methodsA surgical AI software (Theator Inc., Palo Alto, CA) was used to capture and analyse videos of partial nephrectomies performed between October 2023 and April 2024. The platform utilized computer vision algorithms to detect clamp placement and removal, enabling precise WIT measurement. Expert‐reviewed surgical videos served as the ground truth. Platform‐derived WITs were compared to those in surgeon operative reports using paired‐sample t‐tests. Additionally, we analysed the correlation between platform‐derived WITs and postoperative creatinine levels extracted from electronic health records (EHRs) integrated via health level seven (HL7) messaging protocols.ResultsOf 64 eligible cases, 61 were included in the final analysis. Platform‐derived WITs were within 1 min of the ground truth in all procedures, within 30 s in 97%, and within 10 s in over 80%. The mean difference between platform‐derived WITs and ground truth was 8.3 s, significantly lower than the 2.45 min difference for operative reports (p &lt; 0.001). No significant correlation was found between platform‐derived WIT and postoperative creatinine changes, aligning with the view that WIT may not independently determine postoperative renal function. Although not the primary goal of this study, significant correlations were observed between WIT, tumour size and RENAL score.ConclusionThis study demonstrates the high accuracy of a surgical intelligence platform in measuring WIT during partial nephrectomies. The findings support the use of AI‐based surgical time measurement for precise intraoperative documentation and highlight the potential of integrating these data with EHRs to advance research on surgical outcomes.

Impacts of completely endophytic renal masses on perioperative, oncologic, and functional outcomes in robot-assisted partial nephrectomy: a systematic review and meta-analysis.

The objective of this study was to perform a comprehensive pooled analysis aimed at comparing the efficacy and safety of robot-assisted partial nephrectomy (RAPN) between completely endophytic tumors (CERT) and non-completely endophytic tumors (non-CERT). This study adhered rigorously to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to conduct a systematic review and meta-analysis. We performed a systematic search in the PubMed, Embase, Web of Science, and Cochrane Library databases, focusing on studies published in English up to May 2024. Our analysis primarily evaluated key outcomes, specifically perioperative, functional, and oncological outcomes. A total of 2126 patients across six studies were included in the analysis. Compared to non-CERT, CERT was associated with significantly higher rates of major complications (Odds Ratio [OR]: 2.47; 95% CI: 1.14 to 5.34; p = 0.02), longer warm ischemia times (Weighted Mean Difference [WMD]: 3.27min; 95% CI: 0.61 to 5.39; p = 0.02), a greater decline in estimated glomerular filtration rate (eGFR) (WMD: 2.93 ml/min/1.73 m2; 95% CI: 0.75 to 5.11; p = 0.008), and relatively lower trifecta achievement rates (OR: 0.63; 95% CI: 0.41 to 0.96; p = 0.03). However, no statistically significant differences were observed between the two groups in terms of operative time, length of stay, blood loss, transfusion rates, intraoperative complications, overall complications, positive surgical margins, and local recurrence. Although CERT was associated with greater declines in eGFR and lower rates of trifecta achievement, it yielded perioperative, functional, and oncologic outcomes comparable to those of non-CERT in RAPN. Our findings suggest that RAPN for completely endophytic renal masses can achieve acceptable outcomes when performed in centers with substantial expertise in robotic surgery. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=555067, identifier CRD42024555067.

Remote kidney and liver injury after transplantation of lung allografts in an allogeneic mouse model

Background: Remote organ dysfunction is common after lung transplantation and might negatively affect outcome. The local anesthetic ropivacaine was previously demonstrated to attenuate acute rejection after allogeneic lung transplantation in mice. We hypothesized that lung transplantation might result in detectable molecular signs of injury in kidneys and liver and that ropivacaine might attenuate this damage. Methods: Organs from C57BL/6 mice undergoing allogeneic orthotopic single-lung transplantation were procured at postoperative day five and analyzed using western blot and real-time quantitative polymerase chain reaction probing for Src protein tyrosine kinase, STAT3 and bax/bcl-2. During cold ischemia, the allograft had either been flushed with normal saline only or in combination with ropivacaine (1 µM). A non-transplanted group of animals served as baseline controls. Results: The allogeneic stimulus induced by transplantation lead to an increase in Src-phosphorylation and STAT3-expression in kidneys and livers of lung-transplanted mice compared to non-transplanted animals. Bax/bcl-2 as a marker of cellular apoptosis was not affected by the transplantation. In contrast to the findings in the transplanted lungs, the addition of ropivacaine did not have an effect on the examined markers of inflammation in the remote organs. Conclusions: The observed increase in the inflammatory signaling provides first insight into a possible mechanism, by which remote organ dysfunction after lung transplantation might occur.

Grasping time - longevity of vascularized composite allografts.

Despite significant advancements in the field of vascularized composite allotransplantation, challenges, particularly regarding the long-term viability and functionality of vascularized composite allotransplantation (VCA) grafts, persist. This paper provides a review of the current literature on the longevity of VCA grafts, focusing on factors influencing graft survival, immunological considerations and clinical outcomes. Longevity of VCA grafts is influenced by a variety of peri- and postoperative factors including cold ischemia time, human leukocyte antigen matching, environmental exposure, psychosocial factors, adherence, immunosuppression, and complications. Due to the limited number of VCA transplants performed and heterogenous reporting, direct correlation of single factors with VCA outcomes remains inconclusive. Indirect evidence, however, supports their importance. High immunosuppressive burden, frequent occurrence of acute and accumulating cases of chronic rejection remain a significant challenge of the field. Insights gained from this review aim to inform clinical practice and guide future research endeavors with the goal of ameliorating outcomes after VCA transplantation and facilitate wider use of VCA grafts for restoration of tissue defects.

Cold ischemia time alters cell-type specific senescence leading to loss of cellular integrity in mouse lungs

Purpose: Ischemia-reperfusion injury (IRI) is a major challenge in lung transplantation often causing graft dysfunction and chronic airway illnesses in recipients. To prevent potential transplant related complications, strict guidelines were put in place to choose viable donor lungs with minimal risk of IRI. These regulations deem most of the donor organs unfit for transplant which then are donated for research to understand the mechanisms of health and diseases in human. However, resected organs that are being transported undergo cold ischemia that can negatively affect the tissue architecture and other cellular functions under study. Thus, it is important to assess how cold ischemia time (CIT) affects the physiological mechanism. In this respect, we are interested in studying how CIT affects cellular senescence in normal aging and various pulmonary pathologies. We thus hypothesized that prolonged CIT exhibits cell-type specific changes in lung cellular senescence in mice. Methods: Lung lobes from C57BL/6J (n = 5–8) mice were harvested and stored in UW Belzer cold storage solution for 0, 4-, 9-, 12-, 24-, and 48-h CIT. Lung cellular senescence was determined using fluorescence (C12FdG) assay and co-immunolabelling was performed to identify changes in individual cell types. Results: We found a rapid decline in the overall lung cellular senescence after 4-h of CIT in our study. Co-immunolabelling revealed the endothelial cells to be most affected by cold ischemia, demonstrating significant decrease in the endothelial cell senescence immediately after harvest. Annexin V-PI staining further revealed a prominent increase in the number of necrotic cells at 4-h CIT, thus suggesting that most of the cells undergo cell death within a few hours of cold ischemic injury. Conclusions: We thus concluded that CIT significantly lowers the cellular senescence in lung tissues and must be considered as a confounding factor for mechanistic studies in the future.

Oncologic Outcomes and Safety Assessment of Retroperitoneal Laparoscopic Partial Nephrectomy versus Open Partial Nephrectomy in Treating Patients with Localized Renal Cell Carcinoma: A Propensity Score Matching Study.

Surgical intervention is crucial in radical resection of renal cell carcinoma (RCC). Different surgical procedures have different oncologic outcomes and safety in patients with RCC. Therefore, we aimed to investigate the oncologic outcomes and safety of retroperitoneal laparoscopic partial nephrectomy (RLPN) versus open partial nephrectomy (OPN) in treating patients with localized RCC. This retrospective cohort study included 160 patients with localized RCC who underwent either OPN or RLPN from January 2016 to June 2020. Out of these patients, 75 patients were treated with OPN and 85 patients were treated with RLPN. After propensity score matching, 130 patients (65 cases in each group) were finally included in the analysis. Additionally, surgical outcomes, three-year survival rates, and renal function parameters were assessed between the two groups, and the data were statistically analyzed using SPSS. Compared to the OPN group, RLPN demonstrated significantly shorter surgical time, lower estimated blood loss (p < 0.05), and lower incidence of complications (p = 0.024). In contrast, the RLPN group had significantly longer warm ischemia time (p = 0.011) than the OPN group. Furthermore, there were no significant differences in three-year overall survival, disease-free survival, cancer specific survival rates, positive surgical margins, hospitalization time between the RLPN and OPN groups (p > 0.05). The incidence of complications in the RLPN group was significantly lower than that in the OPN group (p = 0.024). Postoperatively, creatinine level was significantly lower following RLPN at one year compared to OPN (p = 0.029). RLPN offers advantages in surgical time, estimated blood loss, and postoperative complications, and it positively affects postoperative renal function, while OPN shows a shorter warm ischemia time. These two approaches result in comparable three-year survival rates. This study provides valuable insights into the oncologic outcomes and safety of RLPN compared to OPN in treating localized RCC.

Impact of tumor dissecting technique on trifecta achievement in patients requiring extended warm ischemia during robot-assisted partial nephrectomy.

To clarify specific factors associated with surgical outcomes in robot-assisted partial nephrectomy (RAPN) that require extended warm ischemia time (WIT), which may have a negative impact, but cannot always be avoided. We included 1,182 patients who had RAPN performed between January 2016 and December 2022 from a prospectively generated multi-institutional RAPN database, divided into normal WIT (nWIT) (≤ 20min; 843 patients) and extended WIT (eWIT) (> 20min; 339 patients) groups. Primary outcome measures were WIT and the Surface-Intermediate-Base (SIB) margin score, which contribute to postoperative trifecta achievement. Results were compared between the two groups using logistic regression. Patients in the eWIT group had larger tumors, higher RENAL nephrometry scores, and lower SIB scores than those of the nWIT group. The trifecta achievement rate was significantly different between the two groups (nWIT: 70.1 vs. 49.0%, p < 0.001). In the nWIT group, WIT (coefficient: -0.105 [standard error 0.020], p < 0.001) and SIB score (coefficient: -0.107 [0.053], p = 0.045) were significant predictors of trifecta achievement. In the eWIT group, the SIB score (coefficient - 0.216 [0.082], p = 0.008) was significantly associated with trifecta attainment, whereas WIT only showed a trend toward significance. Limitations included a lack of long-term survival, renal function, and chronic complications data. For patients with eWIT during RAPN, the tumor dissection technique may be more important than WIT in predicting postoperative outcomes. Further prospective studies are required to confirm our results.

Revisiting the Prognostic Influences of Donor-Recipient Size Mismatch in Deceased Donor Liver Transplantation.

Liver transplantation (LT) outcomes are influenced by donor-recipient size mismatch. This study re-evaluated the impact on graft size discrepancies on survival outcomes. Data from 53 389 adult LT recipients from the United Network for Organ Sharing database (2013-2022) were reviewed. The study population was divided by the body surface area index (BSAi), defined as the ratio of donor body surface area (BSA) to recipient BSA, into small-for-size (BSAi < 0.78), normal-for-size (BSAi 0.78-1.24), and large-for-size (BSAi > 1.24) grafts in deceased donor LT (SFSD, NFSD, and LFSD). Multivariate Cox regression and Kaplan-Meier survival analyses were conducted. The frequency of size mismatch in deceased donor LT increased over the past 10 y. SFSD had significantly worse 90-d graft survival (P < 0.01), and LFSD had inferior 1-y graft survival among 90-d survivors (P = 0.01). SFSD was hazardous within 90 d post-LT because of vascular complications. Beyond 1 y, graft size did not affect graft survival. LFSD risk within the first year was mitigated with lower model for end-stage liver disease (MELD) 3.0 scores (<35) or shorter cold ischemia time (<8 h). The negative impacts on donor-recipient size mismatch on survival outcomes are confined to the first year post-LT. SFSD is associated with a slight decrease in 90-d survival rates. LFSD should be utilized more frequently by minimizing cold ischemia time to <8 h, particularly in patients with MELD 3.0 scores below 35. These findings could improve donor-recipient matching and enhance LT outcomes.

Clinical application and efficacy analysis of robot-assisted laparoscopic tumor enucleation combined with tumor aspiration in the treatment of renal hilar angiomyolipoma

BackgroundFor renal hilar angiomyolipoma, general surgical resection is often quite challenging. The aim of this study is to evaluate the safety and efficacy of an innovative robot-assisted laparoscopic strategy that combines tumor enucleation with tumor aspiration in the treatment of renal hilar angiomyolipoma.MethodsThe clinical data of 38 patients with renal hilar angiomyolipoma who went through robotic tumor enucleation combined with tumor aspiration in the Department of Urology, the Affiliated Hospital of Nanjing University Medical School, from December 2019 to December 2022 were retrospectively analyzed. The basic characteristics, the perioperative variables, intraoperative procedures, and postoperative complications were all recorded. Patients were followed up to evaluate the angiomyolipoma recurrence and the renal function by urologic CT or ultrasound and renal function tests.ResultsAll surgeries were successfully completed without conversion to radical nephrectomy or open surgery. One patient developed urinary extravasation 10 days after surgery, and was readmitted to the hospital for transurethral ureteral stenting considering the injury of the renal collecting system. The median operative time was 181.5 (123.8-206.3) min, the warm ischemia time was 20.0 (17.3–24.0) min, the blood loss was 125 (100.0-262.5) ml, and no patients received blood transfusion during and after surgery. The median hospitalization time was 7.0 (6.0–9.0) days, and the duration of indwelling drainage tube was 2.0 (2.0–3.0) days. The serum creatinine (Scr) on the first day, 3 months, and 6 months after surgery were 55.5 (50.8–62.8) µmol/L, 55.5 (48.0–62.0) µmol/L and 54.0 (51.8–63.5) µmol/L, respectively, and there was no significant difference compared with the preoperative level 56.0 (47.8–60.3) µmol/L. All patients were followed up after surgery, and the urinary CT scan or renal color doppler ultrasound, and renal function were reexamined. The median follow-up time of all patients was 19.0 (14.75-33.0) months, and no local recurrence of angiomyolipoma was seen in all patients.ConclusionsThe surgical strategy of robot-assisted laparoscopic tumor enucleation combined with tumor aspiration is safe and effective in the treatment of renal hilar angiomyolipoma.

Outcomes of Donation After Circulatory Death Heart Transplantation Using Normothermic Regional Perfusion

BackgroundDonation after circulatory death (DCD) with cardiopulmonary bypass for thoracoabdominal normothermic regional perfusion (TA-NRP) has led to increased use of donor hearts. Rejection rates and long-term survival outcomes are not known. MethodsA single-center retrospective cohort review of patients who underwent DCD heart transplantation from January 2020 to December 2023 was performed. Donor and recipient characteristics, operative characteristics, and posttransplantation outcomes were analyzed. Subgroup analysis comparing co-localized vs distant donors and recipients was performed. The primary end point was 1-year survival. Secondary end points included incidences of primary graft dysfunction (PGD), cardiac allograft vasculopathy (CAV), rejection rate, and overall mortality. Our TA-NRP protocol has remained the same, consisting of sternotomy, ligation of aortic arch vessels, establishment of cardiopulmonary bypass, reintubation, resuscitation of the heart, and cold static storage during transport. ResultsIn total, 32 recipients underwent DCD heart transplantation, including 26 isolated hearts, 3 heart-lungs, and 3 heart-kidneys. The median age was 56 years for recipients and 39 years for donors; 21 donors and recipients were co-localized, whereas 11 were distant. One-year survival was 100%. Two patients required mechanical circulatory support for PGD. Four patients experienced grade 2R acute cellular rejection. Five patients had grade 1 CAV at 1 year. On subgroup analysis, distant donors and recipients had longer warm (47 vs 30 minutes; P < .005) and cold (213 vs 76 minutes; P < .005) ischemia times, without any other differences. ConclusionsOutcomes after DCD heart transplantation using TA-NRP remain encouraging with acceptable rates of rejection, PGD, CAV, and survival at 1 year.