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A persistent challenge that has limited access and delivery of digit replantation surgery is timing, as ischemia time has traditionally been considered an important determinant of success. However, reports that the viability of amputated digits decreases after 6 hours of warm ischemia and 12 hours of cold ischemia are largely anecdotal. This review evaluates the quality and generalizability of available evidence regarding ischemia times after digit amputation and reported outcomes of “delayed” replantation. We identify substantial limitations in the literature supporting ischemia time cutoffs and recent evidence supporting the feasibility of delayed digit replantation. The current treatment approach for amputation injuries often necessitates transfers or overnight emergency procedures that increase costs and limit availability of digit replantation nationwide. Evidence-based changes to digit replantation protocols could lead to broader availability of this service, as well as improved care quality.

OBJECTIVES To review a large, multicenter experience to identify the current salvage and amputation rates of these combined injuries and, where possible, the variables that predict amputation. DESIGN Retrospective. SETTING Nine trauma centers. PATIENTS This study involved 199 patients presenting to 9 trauma centers with orthopaedic and vascular injuries resulting in ischemic limbs for whom the orthopaedic service was involved with the decision for salvage versus amputation. RESULTS We reviewed 199 patients, 17-85 years of age. One hundred seventy-two of the injuries were open. Thirty-eight patients (19%) were treated with amputation upon admission as they were deemed to be unsalvageable. Of the remaining 161 patients who had attempted salvage, 36 (30%) required late amputation. Closed injuries were successfully salvaged in 25 of 27 cases (93%). The highest rate of amputation was in tibia fractures with a combined amputation rate of 62%. In those attempted to be salvaged, 21 of 48 (44%) required amputation. The ischemia time for successful salvage was significantly less, P = 0.03. One hundred twenty-four patients had their definitive vascular repair before the bony reconstruction. There were 15 vascular complications, of which 13 (86%) had the definitive vascular repair performed before the definitive osseous repair, although this was not statistically significant. CONCLUSIONS In this series of combined orthopaedic and vascular injuries, we found a high rate of acute and late amputations. It is possible that other protocols, such as shunting and stabilizing the osseous injury, before vascular repair may benefit limb salvage, although this needs more study. LEVEL OF EVIDENCE Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

International audience; Many variables impact islet isolation, including pancreas ischemia time. The ischemia time upper limit that should be respected to avoid a negative impact on the isolation outcome is not well defined. We have performed a retrospective analysis of all islet isolations in our center between 2008 and 2018. Total ischemia time, cold ischemia time, and organ removal time were analyzed. Isolation success was defined as an islet yield ≥200 000 IEQ. Of the 452 pancreases included, 288 (64%) were successfully isolated. Probability of isolation success showed a significant decrease after 8 hours of total ischemia time, 7 hours of cold ischemia time, and 80 minutes of organ removal time. Although we observed an impact of ischemia time on islet yield, a probability of isolation success of 50% was still present even when total ischemia time exceeds 12 hours. Posttransplantation clinical outcomes were assessed in 32 recipients and no significant difference was found regardless of ischemia time. These data indicate that although shorter ischemia times are associated with better islet isolation outcomes, total ischemia time >12 hours can provide excellent results in appropriately selected donors.

Background: High-throughput transcript sequencing plays an important role in the study of hepatocellular carcinoma (HCC) occurrence and development. High-quality biospecimens, especially high-quality RNA, are the most basic prerequisites for obtaining good transcript sequencing data. Our purpose was to explore the treatment conditions of in vitro ischemic tissue samples that can be used to obtain high-integrity RNA before freezing the samples in liquid nitrogen. Materials and Methods: Postoperative tumor tissues (T) and adjacent normal tissues (AN) from 50 HCC patients were randomly selected from May 5, 2017, to June 15, 2017. Postoperative tissue specimens from each HCC patient were stratified by tissue type (T or AN), ischemia time (minutes), and ischemia temperature (°C) into 16 groups: T-4°C-15 minutes, T-4°C-30 minutes, T-4°C-60 minutes, T-4°C-120 minutes, T-24°C-15 minutes, T-24°C-30 minutes, T-24°C-60 minutes, T-24°C-120 minutes, AN-4°C-15 minutes, AN-4°C-30 minutes, AN-4°C-60 minutes, AN-4°C-120 minutes, AN-24°C-15 minutes, AN-24°C-30 minutes, AN-24°C-60 minutes, and AN-24°C-120 minutes. RNA integrity was detected by RNA integrity number (RIN) and 1% agarose gel electrophoresis. Results: At an ischemia temperature of 4°C and ischemia time of >30 minutes, the RIN of T began to decrease. RIN also gradually decreased in T at an ischemia temperature of 4°C and in both T and AN at an ischemia temperature of 24°C for ischemia times 15, 30, 60, and 120 minutes. For an ischemia time ≤15 minutes and ischemia temperature 4°C or 24°C, the RINs of T and AN were significantly different. Furthermore, at ischemia temperature 4°C and ischemia time 30 and 60 minutes or ischemia temperature 24°C and ischemia time 30 minutes, the RIN of T was higher compared with AN. However, there was no significant difference in RIN between T and AN under other treatment conditions. Conclusions: Tissue quality is adversely affected by ischemia time and ischemia temperature. Therefore, temporary ischemia time (≤15 minutes) before snap freezing is key for maintaining high-integrity RNA in HCC tissues.

Traumatic penis amputation is a urological emergency. Although repair techniques have been well described in literature, failure of replantation and its causes are poorly understood and reported. The aim of this study is to evaluate the treatment and prognosis of microsurgical replantation of penile amputation with a relative long-term ischemia, and review related literatures to summarize relevant clinical experiences. We report two cases of penile amputation and microsurgical replantation performed in our hospital in August 2016. In the first case, the patient was injured by sharp scissors due to family conflict, while in the second case, it was a mechanical injury. For both cases, microsurgical approaches were adopted. After the microsurgical replantation, both the patients recovered well and showed normal urination, erectile function, return of sensations and satisfactory cosmetic appearance. With the development of microsurgical techniques, the successful re-anastomosis of blood vessel and nerve can increase the survival and functional recovery of the penis even in cases exceeding 10 hours of ischemia. This provides greater possibility of graft survival with minimum complication.

Despite improvements in organ preservation techniques and efforts to minimize the duration of cold ischemia, ischemia–reperfusion (IR) injury remains associated with poor graft function and long-term survival in kidney transplantation. We recently demonstrated a clinically significant day-time variation in myocardial tolerance to IR, transcriptionally orchestrated by the circadian clock. Patient and graft post-transplant survival were studied in a cohort of 10,291 patients first transplanted between 2006 and 2017 to test whether kidney graft tolerance to IR depends on the time-of-the-day of clamping/declamping, and thus impacts graft and patient survival. Post-transplant 1- and 3-year survival decreased with increasing ischemia duration. Time-of-the-day of clamping did not influence outcomes. However, night-time (vs. day-time) declamping was associated with a significantly worse post-transplant survival. After adjustment for other predictors, night-time (vs. day-time) declamping remained associated with a worse 1-year (HR= 1.26 (1.08–1.47), p = 0.0028 by Cox multivariable analysis) and 3-year (HR= 1.14 (1.02–1.27), p = 0.021) outcome. Interestingly, the deleterious impact of prolonged ischemia time (&gt, 15 h) was partially compensated by day-time (vs. night-time) declamping. Compared to night-time declamping, day-time declamping was associated with a better prognosis of kidney transplantation despite a longer duration of cold ischemia.

Nephron mass preservation is a key determinant of functional outcomes after partial nephrectomy (PN), while ischemia plays a secondary role. Analyses focused specifically on recovery of the operated kidney appear to be most informative, yet have only included limited numbers of patients.To evaluate the relative impact of parenchymal preservation and ischemia on functional recovery after PN using a more robust cohort allowing for more refined perspectives about ischemia.A total of 401 patients managed with PN with necessary studies were analyzed for function and nephron mass preserved specifically within the kidney exposed to ischemia.PN.The nephron mass preserved was measured from computed tomography scans2 mo before and 3-12 mo after PN. Patients with two kidneys were required to have nuclear renal scans within the same timeframes. Recovery from ischemia was defined as the percent function preserved normalized by the percent nephron mass preserved. Pearson correlation was used to evaluate relationships between functional recovery and nephron mass preservation or ischemia time. Multivariable linear regression assessed predictors for recovery from ischemia.The median tumor size was 3.5cm and the median RENAL score was 8. Cold and warm ischemia were utilized in 151 and 250 patients, and the median ischemia time was 27 and 21min, respectively. The function preserved was strongly correlated with nephron mass preserved(r=0.63; p0.001). Median recovery from ischemia was significantly higher for hypothermia (99% vs 92%; p0.001) and remained consistently strong even with longer duration. Multivariable analysis demonstrated that recovery from ischemia, which normalizes for nephron mass preservation, was significantly associated with ischemia type and duration (both p0.05). However, each additional 10min of warm ischemia was associated with only a 2.5% decline in recovery from ischemia. Limitations include the retrospective design.Our data suggest that functional recovery from clamped PN is most reliable with hypothermia. Longer intervals of warm ischemia are associates with reduced recovery; however, incremental changes are modest and may not be clinically significant in patients with a normal contralateral kidney.Functional recovery after clamped partial nephrectomy is primarily dependent on preservation of nephron mass. Recovery is most reliable when hypothermia is applied. Longer intervals of warm ischemia are associated with reduced recovery; however, the incremental changes are modest.

We evaluated the effects of three-dimensional virtual planning and the use of a plate-embedded surgical guide in mandibular reconstruction with microvascular fibula flaps.We retrospectively reviewed 35 patients who underwent primary mandibular reconstruction with a free fibula flap. They were divided into three groups according to the therapy they received. In group A, 12 patients underwent reconstruction using the modified surgical guide system, including virtual surgeries, pre-bent titanium plates, screw-predesignated cutting guides for mandibular and fibular osteotomies, and plate-embedded shaping guides. In group B, 14 patients underwent reconstruction using the common surgical guide system, including virtual surgeries, cutting guides and pre-bent plates. In group C, 9 patients underwent reconstruction based on the surgeon's experience. All cases were reviewed for the total operative time, ischemia time of the fibula flaps, accuracy of surgery, and postoperative complications.All of the fibula flaps survived. In group A, the ischemia time was shorter than that of groups B and C (P .05). The average gonion and condyle shift was lower in group A than in groups B and C (P .01).Application of the screw-predesignated and plate-embedded surgical guide system can reduce the ischemia time and operation time in mandibular reconstruction with a fibula flap, and can increase reconstruction accuracy. This method is a precise and highly reliable technique for improving the clinical outcome of mandibular reconstruction.

One of the keys to successful cardiac transplantation is preservation of the heart during explantation, transport and implantation. To date the most commonly used method has been cold static storage and this currently remains the only method available for pediatric recipients. However, there has long been interest in continuous perfusion of the donor organ during the ex vivo period to mitigate the effects of ischemia and this is now becoming a clinical reality for adult recipients with good short and early midterm results. Data to date however suggests that the greatest benefit lies in preserving marginal organs, especially those following circulatory death, or when a prolonged ischemic time can be predicted.

Renal ischemic time is one of the most variable risk factors in partial nephrectomy (PN). Our purpose was to investigate if intermittent ischemia could decrease renal impairment in the process of PN in porcine model and explore the feasibility of this surgical procedure in nephrectomy. A kidney ischemia-reperfusion injury model was successfully established in six pigs under laparoscopic surgery. One kidney of each pig was continuously ischemic, and intermittent ischemia was administered to the kidney of another side. Laparoscopic renal artery occlusion was applied to each kidney for 120 minutes. Intermittent ischemia was 15/3 minutes of cycles (ischemia for 15 minutes and reperfusion for 3 minutes). Microdialysis technique, immunohistochemistry, and histopathology were used to evaluate the extent of renal function injures. The concentration of glycerol in intermittently ischemic group was significantly lower than that in continuously ischemic group (

Background: Ischemic time has prognostic importance in ST-elevation myocardial infarction patients. Mobile intensive care unit use can reduce components of total ischemic time by appropriate triage of ST-elevation myocardial infarction patients. Methods: Data from the Acute Coronary Survey in Israel registry 2000–2010 were analyzed to evaluate factors associated with mobile intensive care unit use and its impact on total ischemic time and patient outcomes. Results: The study comprised 5474 ST-elevation myocardial infarction patients enrolled in the Acute Coronary Survey in Israel registry, of whom 46% ( n=2538) arrived via mobile intensive care units. There was a significant increase in rates of mobile intensive care unit utilization from 36% in 2000 to over 50% in 2010 ( p1 (odds ratio=1.32, pConclusions: Among patients with ST-elevation myocardial infarction, the utilization of mobile intensive care units is associated with increased rates of primary reperfusion, a reduction in the time interval to reperfusion, and a reduction in one-year adjusted mortality.

Our understanding of the potential impact of ischemia time on renal function during nephron-sparing surgery (NSS) is based on decades of low-quality evidence. Recent studies have shown that the baseline quality of the renal parenchyma and the quantity of parenchyma remaining, rather than duration of ischemia, are more important in predicting renal functional recovery. A prospective clinical trial evaluating actual renal parenchyma under clamp conditions during NSS showed minimal structural and functional changes that were reversible and were not associated with duration of ischemia. Patients with known preoperative kidney disease should be optimized before surgery and care should be taken intraoperatively to preserve the maximum amount of healthy parenchyma. A thorough evaluation of evidence is warranted before setting or changing surgical practice and approach. Patient summary: This mini-review reveals that a limited duration of ischemia during nephron-sparing surgery for kidney cancer does not have a significant impact on renal function. Baseline renal function and the amount of parenchyma preserved appear to play a more important role in predicting postoperative renal function.

Background During free-tissue transfer for scalp reconstruction, pedicle lengthening may be required when finding a recipient vessel is difficult because of defects from previous surgery. Arteriovenous (AV) bundle interposition grafting is a good option. This study compared 2 sequences of AV bundle interposition grafting when flap pedicle lengthening is needed. Methods Two anastomosis methods were used. In the recipient lengthening type (R type), the flap was harvested and the AV bundle was harvested from a donor vessel for lengthening. In the flap lengthening type (F type), the flap was harvested first. Next, in contrast to that in the R type method, the authors performed anastomosis with a flap pedicle and bundle before the AV bundle was harvested. Results The mean flap pedicle length was 8.75 cm (range, 5-11 cm). The AV bundle had a mean length of 9.25 cm (range, 6-13 cm), meaning that 13 cm of additional pedicle length can be added. The mean length of the extended vascular pedicle was 18 cm (range, 14-23 cm). Conclusion This study compared the results of F type and R type AV bundle interposition grafting. The F type allowed easy monitoring of the anastomosis of the flap pedicle and ensured flap stability by reducing continuous ischemic time. Finally, this study confirmed the efficacy and safety of the AV bundle interposition graft in scalp reconstruction.

Objectives: We evaluated the efficacy of sutureless laparoscopic partial nephrectomy (LPN), using a fibrin gel in order to minimize renal ischemia time and preserve kidney function. Materials and Methods: Nineteen patients (mean age 58.3 ± 7.1) undergoing sutureless LPN using a fbrin gel were compared with a control group consisting of 21 patients (mean age 57.9 ± 7.5) subjected to LPN with standard suturing. Intraand post-operative data for the two groups were compared. The following parameters were recorded: patient demographics, Charlson Comorbidity Index, tumor characteristics according to the RENAL score, warm ischemia and operative times, estimated blood loss, mean hospital stay, post-operative complications referring to the Clavien-Dindo classification, renal function parameters pathologic and follow-up data. The main outcome measure was renal ischemia time and maintenance of kidney function. Results: Median warm ischemia time was 13 minutes (range 11-19) in the group treated with fibrin gel and 19 (range 17- 29) in the control group, with a statistically significant difference (p < 0.001). The two groups were homogeneous in terms of the Charlson Comorbidity Index (4.6 vs 4.8) and RENAL score (9.6 vs 9.4). Median operative time differed significantly in the two groups, 183 minutes (range 145-218) in the group treated with fibrin gel and 201 (range 197-231) in the control group (p < 0.001). A negative surgical margin was reported in 18 patients (94.7%) in the group treated with fibrin gel and in 21 patients (100%) in the control group. No difference in renal function was found between the two groups. Conclusions: Sutureless LPN with fibrin gel can reduce warm ischemia and total operative time while preserving kidney function.

The use of robotic techniques in laparoscopic donor nephrectomy currently tends to involve a longer ischemia time without clear advantages, and the cost of robotic surgery is significantly higher. If only one robot is available, then unnecessary prolongation of cold ischemia time also occurs, as the donor must first be undocked to dock the recipient. The combination of laparoscopic donor nephrectomy with parallel initiation of robot-assisted situs preparation and exposure of the renal vessels appears to be the best current approach to safe and cost-effective donor nephrectomy and subsequent robot-assisted kidney transplantation without wasting any time.

To accurately predict the ischemic time (IT) and select candidates for transabdominal laparoscopic partial nephrectomy (LPN).Transabdominal LPN was performed for 135 Japanese patients with renal masses7 cm in diameter between 2009 and 2016 by a single surgeon in a single institute. The renal parenchymal sutures were done with a combination of felt, Hem-o-lok and Lapra-Ty. The original R.E.N.A.L. nephreometry score (NS) was modified as follows. In terms of the tumor size (R), 1, 2, and 3 points were given for ≤2.5, 2.5-4, and4 cm, respectively. For tumor location (A), 1, 2, and 3 points were given for anterior, on the coronal plane, and posterior, respectively.The median IT was 24.6 minutes. Using the original NS, 64, 65, and 6 patients were categorized into low (4-6), moderate (7-9), and high (10-12) complexity, respectively. With the modified NS, 42, 75, and 18 patients were categorized into low (5-7), moderate (8-11), and high (12-15) complexity, respectively. Pearson's correlation coefficient (R) between the original NS and IT was 0.297, whereas the R was improved to 0.388 when the modified NS was employed. If the modified NS was low complexity, 95.2% achieved IT30 minutes. Of them, none showed IT ≥30 minutes if the body mass index was25 kg/mThe modified NS had a better correlation to the IT than the original NS for patients with tumor sizes7 cm who underwent transabdominal LPN. The modified NS with body mass index is a practical tool to select candidates for transabdominal LPN.

Considerable effort has been made to improve differentiated diagnostics as well as personalized treatment for colorectal cancer patients. High-quality fresh frozen tissue is often required to investigate relevant molecular signatures in these patients. In RNA expression studies, the "RNA integrity number" is widely accepted as a reliable marker of RNA quality. Here, we investigate the feasibility of obtaining high-quality tissue from a colon cancer biobank and the impact of in vivo ischemic time and various technical and clinicopathological factors on RNA quality. Biopsies were obtained immediately following the tumor removal. The time from clamping the main arterial supply to resection and removal of the tumor was used to estimate the in vivo ischemic time. We did not observe a significant difference in RNA quality between normal tissue and tumor tissue. We observed a significant correlation between in vivo ischemic time and RNA quality in normal tissue (r = -0.24, p0.001) but not in tumor tissue. Male gender and laparoscopic procedure were also significantly associated with lower RNA quality in normal tissue only. In tumor tissue, poor differentiation was associated with low RNA quality. In conclusion, in vivo ischemic time, surgical procedure, and gender have minor but significant effects on the quality of RNA from normal colon tissue but not tumor tissue. Poorly differentiated tumors are associated with lower RNA quality. Although its impact is low, it can still be considered to note in vivo ischemic time in colon cancer specimen procurement.

BackgroundAlthough the intermittent Pringle maneuver is used for major transplant surgery, traumas, and hepatic protection, long ischemia time and reperfusion may limit some protection in Wistar rats. The aim of the study was to evaluate the protection effects of intermittent clamping in the total hepatic pedicle after a long period of ischemia and reperfusion in Wistar rats.MethodsForty-two male Wistar rats, weighing ±327.7 g, were anesthetized intravenously with sodium thiopental and given a U-shaped incision in the abdomen. The total hepatic pedicle was isolated and subjected to clamping with a microvascular clamp. Groups included were the continuous group (CG, n = 14, 40 minutes of ischemia/40 minutes of reperfusion); the intermittent group (IG, n = 14, 4 cycles a 10 minute ischemia/reperfusion 10 minutes); and the sham group (SG, n = 14, 80 minutes of observation time). Blood collection for transaminase dosage was carried out, and hepatic biopsy specimens were taken for mitochondrial respiration and histological evaluation.ResultsIn groups CG and IG, aspartate aminotransferase and alanine aminotransferase enzymes were elevated in comparison to group SG (P < .008); mitochondrias, when stimulated by use of adenosine diphosphate or carbonylcyanide p-trifluoromethoxyphenylhydrazone, had a significant decrease in mitochondrial respiration (P < .05), and the respiratory control ratio in the ischemic groups was lower (P < .03) when compared with the GS. On histological examination, 100% of the GC had lesions: 33% focal hemorrhagic necrosis, 17% sinuzoidal congestion and/or vacuolization, and 50% venous congestion; in the IG, 100% had lesions: 43% sinusoidal congestion and/or vacuolization and 57% venous congestion.ConclusionsThe intermittent total hepatic pedicle clamping for a long period of time in the Wistar rats had no efficacy in protection of liver injury.

SummaryThe suitable size of a graft is a key element in the success of liver transplantation. A small-for-size liver graft is very likely to sustain a significant degree of injury as a result of ischemia, preservation, reperfusion, and rejection. Usually, small-for-size grafts are a concern in living-donor liver transplantation rather than in deceased-donor liver transplantation. Here, we describe the successful transplantation of a liver from a 2-year-old deceased donor to a 61-year-old male recipient who suffered from liver failure related to hepatitis B. No report of successful deceased-donor liver transplantation with discrepancies between donor and recipient age and size to such an extent has been found in the literature. Despite unusually large discrepancies, with effort in minimizing the ischemic time, revised surgical techniques, and strong regenerative power of the “young” graft, the old patient's liver function gradually returned to normal. This again proves that the definition of a “suitable graft” evolves with time and experience.

Severed tissues should be replanted within 6 h at room temperature (20–25 °C), as irreversible necrosis of the muscles occurs because of ischemia. The time can be increased to 12 h if refrigerated (4 °C). The ischemia time for fingers without muscles could be 8 h at room temperature and 12 h under refrigeration. The replantation of a finger whose warm ischemia time is over the time limit is called late replantation. There are very few successful reports of late replantation, and most of these are case reports.

Prolonged graft ischemia may be a risk factor for early rejection post-HTx, but this has not been well studied in children. Furthermore, factors moderating the association between IT and early rejection have not been investigated. From 2004 to 2012, pediatric HTx recipients (n = 2381) were identified from the UNOS database. A ROC curve determined the optimal IT discriminating patients by the presence of early rejection. Separate univariate analyses identified factors associated with: (i) early (prior to hospital discharge) rejection, and (ii) IT. A multivariable logistic regression assessed independent risk factors for early rejection. We included interaction terms to evaluate whether IT's independent risk effect on early rejection is moderated via interaction with associated factors found in univariate analysis. Longer IT was associated with an increased risk of early rejection. In multivariable analysis, IT > 3.1 hours was an independent risk factor for early rejection (AOR 1.44, P = .01). No interaction terms between IT and any associated factors were significant. Longer IT is an independent risk for early rejection in pediatric HTx recipients. Better understanding the association between IT and early rejection may identify interventions to mitigate this risk.

Both authors contributed equally to this work.Primary abdominal wall closure following small boweltransplantation is frequently impossible due to con-traction of the abdominal domain. Although abdomi-nalwalltransplantationwasreported10yearsago,thistechnique has not been widely adopted, partly due toits complexity, but largely because of concerns thatstoring the abdominal allograft until the end of aprolongedintestinaltransplantprocedurewouldcausesevereischemia-reperfusioninjury.Wereportsixcasesof combined small bowel and abdominal wall trans-plantation where the ischemic time was minimized byremotely revascularizing the abdominal wall on theforearm vessels, synchronous to the intestinal proce-dure. When the visceral transplant was complete, theabdominal wall was removed from the forearm andrevascularizedontheabdomen(n¼4),orusedtoclosethe abdomen while still vascularized on the forearm(n¼2). Primary abdominal wall closure was achievedin all. Mean cold ischemia was 305min (300–330min),and revascularization on the arm was 50min (30–60min). Three patients had proven abdominal wallrejection, all treated successfully. Immediate revascu-larization of the abdominal wall allograft substantiallyreduces cold ischemia without imposing constraintson the intestinal transplant. Reducing storage timemay also have benefits with respect to ischemia-reperfusion-related graft immunogenicity.Keywords: Abdominal wall, composite vascularizedallograft, ischemiaAbbreviations: CVA, composite vascularized allograft;LAD, loss of abdominal domain; UW, University ofWisconsinReceived 18 November 2013, revised 11 February 2014and accepted for publication 23 February 2014

Purpose Efforts to increase the number of viable donors, such as ex vivo lung perfusion and donation after circulatory death, are likely to significantly alter allograft ischemic time distributions. As such, understanding the impact allograft ischemia has on short and long-term outcomes will be key in determining best practices going forward. Methods We conducted an ISHLT database study of adult bilateral lung transplant recipients between January 1, 2006 and June 30, 2016. We evaluated for an association between first and second lung ischemic time and short- and long-term outcomes post-transplant. We also performed regression modeling to evaluate factors associated with prolonged ischemic time. Results 13,183 recipients were included in the final analysis. Prolonged first but not second lung ischemic time was associated with decreased unadjusted 30-day survival (log-rank p=0.048) and higher rates of treated acute rejection in the first post-transplant year (p Conclusion First allograft ischemic time appears more strongly associated with increased 30-day and 1-year mortality as well as prolonged index hospitalization and increased acute rejection in the first year. This suggests that, in bilateral lung recipients, first lung ischemic time is more clinically relevant to allograft and patient outcomes.

Patients with unrecognized or untreated extremity compartment syndrome are at high risk of amputation and the rates following major extremity vascular injury are high. Despite this, no clear evidence exists supporting the use of prophylactic fasciotomy. The procedure itself is associated with significant morbidity. Risk factors such as ischemia time, location of injury, concurrent injuries, and hypotension should be used to stratify which patients are most likely to benefit.

The fast label-free detections of the extent and degree of cerebral ischemia have been the difficulties and hotspots for precise and accurate neurosurgery. We experimentally demonstrated the terahertz (THz) transmission imaging of the fresh cerebral tissues at different ischemic stages within 24 hours. With a CO2 laser pumped continuous-wave THz imaging system operating at 2.52 THz, THz imaging could distinguish the ischemic cerebral tissues from the normal cerebral tissues. It was indicated that the transmittance of the THz wave for ischemic cerebral tissues was lower than that for normal cerebral tissues. As the ischemic time increased, the ischemic areas became larger and diffused. Compared to the traditional triphenyltetrazolium chloride-stained (TTC-stained) images, the ischemic tissues can been detected using THz wave with a high sensitivity as early as the ischemic time of 2 hours. Thus, THz imaging has a great potential in recognition of cerebral ischemia and it may become a new method for intraoperative real-time guidance, recognition in situ, and precise excision.

The fact that kidney is sensitive to ischemia/reperfusion (I/R) injury had encouraged us to compare the conventional histology and differential scanning calorimetry (DSC) methods in renal structural changes following experimental warm I/R models. Our histological findings showed that longer warm I/R period caused more severe damage in structure of kidney. The thermal parameters (transition temperature, calorimetric enthalpy) of I/R injury reflected the histological results. These processes correlated with the ischemia time and the degree of injury was more serious after reperfusion periods compared to normal kidney structure, which provides basis for further investigation in different kidney stress models.

Background. Composite tissue allotransplantation (CTA) may restore a variety of tissue defects, but carries the potential risks of graft failure and/or immunosuppression-related complications. Ischemia-reperfusion injury has been documented in CTA is known to contribute to acute rejection of solid organ grafts. This study describes the influence of subcritical ischemic time (ie, ischemia sufficient to generate reversible cell damage) on signs of rejection of musculocutaneous allograft components of subcritical ischemic time, namely, ischemia sufficient to generate reversible cell injury. Although skin is considered the most antigenic component of a composite allograft and is currently used for rejection surveillance, muscle and adipose are more susceptible to ischemia-related injury. Methods. Vascularized epigastric flaps were transplanted from WKY to Fisher 344 rats after 1 or 3 hours of ischemia. Biopsies taken on postoperative day 6 were graded for signs of acute rejection according to criteria modified from previously published grading systems for CTA rejection. Results. Skin and muscle exposed to 3 hours of ischemia showed significantly higher rejection scores than after 1 hour of ischemia, as evidenced by a more aggressive diffuse lymphocytic infiltration with disruption of tissue architecture. The rejection score in skin with 3-hour ischemia was 5.0 ± 0.1 versus 3.7 ± 0.2 with 1-hour (Mann-Whitney U test; P

Item does not contain fulltext BACKGROUND: Under ideal circumstances, creation of the anastomosis during free flap transfer is a routine task and can be performed under short ischemia time. However, vessels may be in suboptimal state due to atherosclerosis, radiotherapy or trauma, increasing difficulties regarding receptor vessel identification, and anastomosis which in turn may lead to lengthening of ischemia time resulting in postoperative wound problems or even flap loss. In the current pilot study, a modified heart-lung machine was assembled to achieve continuous oxygenated extracoporeal perfusion using porcine myocutaneous rectus abdominis flaps, aimed at minimizing tissue damage occurring during ischemia time. MATERIALS AND METHODS: Different pilot test groups with n = 2 were created, including oxygenated perfusion with heparinized autologous blood or organ preservation solutions. Control groups included short flush with preservation solution followed by cold storage. RESULTS: Flaps were successfully attached to the modified heart-lung machine while maintaining stable flow throughout the 24-h experiments. Flaps undergoing continuous oxygenated perfusion with preservation solutions showed minimal or no signs of cell necrosis during the 24-h experiment, in contrast to using heparinized autologous blood or flushing and cold storage. CONCLUSIONS: The use of a modified heart-lung machine for oxygenated perfusion of free flaps provides new possibilities to minimize tissue damage during ischemia time, and further study of its use is warranted.

A rabbit ear ischemic model was created using a minimally invasive surgical technique. On one ear, three small skin incisions were made on the vascular pedicles about 1 cm from the base of the ear. The central and cranial arteries were ligated and divided along with their accompanying nerves. A circumferential subcutaneous tunnel was made through the incisions to cut subcutaneous tissues, muscles, nerves, and small vessels. The other ear was used as a normal control. Wounds were made on the ventral side of the ear. Twenty-two rabbits (14 young adults, four aged, and four diabetic) were used. In the 26 pairs of wounds in young adult rabbits, the mean healing time on the ischemic ear was 20.5+/-3.4 days vs. 14.9+/-1.6 days on the normal ear (mean+/-SD) when normal saline was used as a dressing. Tissue high-energy phosphate contents were higher in the normal ear than in the ischemic ear. The skin temperature on the ischemic ear was 1-7 degrees C lower than that on the normal ear. Wound-healing times were longer in the aged and diabetic rabbits, but no complications occurred in these rabbits. The model created by minimally invasive procedure results in little skin disruption, a longer ischemic time, and a higher success rate as compared with many other models. It can be used in normal animals as well as aged animals, and for the first time, was used successfully in diabetic animals.

In many clinical settings, the duration of renal ischemia and therefore the outcome of acute renal failure cannot be determined adequately. Renal ischemia reperfusion injury is known to shorten telomeres and upregulate stress-induced genes, such as the cyclin-dependent kinase (CDK) inhibitor p21. So far, the expression and role of CDK inhibitors, as well as mouse telomerase reverse transcriptase (mTERT), has not been investigated in a model with variable lasting ischemic periods. Male C57Bl/6 mice were subjected to renal ischemia reperfusion injury by clamping both renal pedicles for 10, 20, 30, and 45 min, and the kidneys were allowed to be reperfused for 3, 24, and 48 h. Expression of different CDK inhibitors and mTERT was evaluated. Mice developed signs of acute renal failure linear to the duration of the ischemic period. Real-time PCR revealed that mTERT was only significantly upregulated in kidneys after short ischemic periods (20 min). In contrast, p21 was constantly upregulated in kidneys after long ischemic intervals (30 and 45 min), but not in kidneys, which were clamped for shorter periods. Mainly, tubular cells contributed to the observed increase in p21 expression. Targeting p21 via the selective p53 inhibitor pifithrin-α was able to prevent acute renal failure when administered immediately before ischemia. The expression of another CDK inhibitor, namely p16, was differentially regulated, depending on the time of reperfusion. Taken together, we detected mTERT and p21 as “indicator” genes for short and long ischemic intervals, respectively. These two proteins might also be possible new therapeutic targets in the treatment and prevention of acute renal failure.

Background The liver is the most commonly injured organ in blunt abdominal trauma. Although major hepatic bleeding may be partially controlled with portal triade clamping (the Pringle’s maneuver), continuous prolonged clamping results in liver ischemia. Objectives The purpose of this study was to determine the safe time of Pringle maneuver based on pathologic changes of liver in rabbit models. Materials and Methods In an experimental study, 20 New-Zealand white rabbits were selected. In laparotomy, a blunt dissector was passed through the foramen of Winslow and the hepato-duodenal ligament encircled with an umbilical tape. En masse Pringle maneuver was performed using atraumatic flexible clamps. Rabbits were divided into four groups based on Pringle maneuver time (30 minutes, 45 minutes, 60 minutes, and 75 minutes). A hepatic biopsy was performed at the beginning of operation. The degree of tissue injury was evaluated using blood markers. Results There were five rabbits in each group. At the end of 60 minutes ischemia, only minor alterations were observed in pathological specimens. At the end of 75 minutes, hepatocyte damage and necrosis were observed. The serum levels of alanine aminotransferase (Group A: P = 0.02; Group B: P = 0.01; Group C: P = 0.0002; Group D: P = 0.01) and Aspartate aminotransferase (Group A: P = 0.03; Group B: P = 0.002; Group C: P = 0.0004; Group D: P = 0.0003) were significantly increased post-operatively. The maximum level was in the first day after operation. Conclusions Continuous portal triade clamping (the Pringle maneuver) during liver ischemia (30 and 45 minutes) in rabbits resulted in no ischemic change. Increasing time of clamping to 30 minutes was safe in intermittent Pringle maneuver.

Background Ischemic postconditioning (IPostC), has been proposed as a useful approach to reduce infarct size in all species, but its clinical utility remains unclear. Objective To investigate the role played by the protocol used on the efficacy of IPostC in protecting the diseased human myocardium. Methods Myocardial atrial samples from patients were subjected to a 90 min ischemia/120 min reoxygenation followed by different IPostC protocols to investigate the role of the time of ischemia (30, 60, 90 and 120 s) and the number of cycles (1, 2, 3 and 4) with 60 and 120 s of total ischemic time. Muscles were also subjected to ischemic preconditioning (IPreC). The release of lactate dehydrogenase (LDH) and the measurement of tetrazolium bromide (MTT) were determined. Results IPostC increased the LDH and decreased the MTT values from those of control, independently of the duration of the conditioning ischemia. LDH and MTT values also worsened by augmenting the number of IPostC cycles whereas they were significantly improved by IPreC. However, analysis of individual results indicated that in approximately 1/3 of the cases IPostC exhibited some degree of protection especially in the presence of increased ischemic injury. Conclusions The present findings show that IPostC of the human myocardium may be influenced by the protocol used and also by the degree of the preceding ischemic injury. IPostC was beneficial in approximately 1/3 of the cases; however in the remaining cases it increased ischemic damage and, therefore, these results raise a word of caution on its broad clinical use.

BACKGROUND:Remote ischemic conditioning (RIC) is a known manual conditioning to decrease ischemic reperfusion injury (IRI) but not increase ischemic time. Here we tried to establish a rat RIC model of liver transplantation (LT), optimize the applicable protocols and investigate the protective mechanism. METHODS:The RIC model was developed by a standard tourniquet. Sprague-Dawley rats were assigned randomly to the sham operated control (N), standard rat liver transplantation (OLT) and RIC groups. According to the different protocols, RIC group was divided into 3 subgroups (10 min×3, n = 6; 5 min×3, n = 6; 1 min×3, n = 6) respectively. Serum transaminases (ALT, AST), creatine kinase (CK), histopathologic changes, malondialdehyde (MDA), myeloperoxidase (MPO) and expressions of p-Akt were evaluated. RESULTS:Compared with the OLT group, the grafts subjected to RIC 5min*3 algorithm showed significant reduction of morphological damage and improved the graft function. Also, production of reactive oxygen species (MDA) and neutrophil accumulation (MPO) were markedly depressed and p-Akt was upregulated. CONCLUSION:In conclusion, we successfully established a novel model of RIC in rat LT, the optimal RIC 5min*3 algorithm seemed to be more efficient to alleviate IRI of the liver graft in both functional and morphological categories, which due to its antioxidative, anti-inflammation activities and activating PI3K Akt pathway.

OBJECTIVE Allocation criteria changed in 2000 as a result of Germany's new transplantation law. Before, thoracic organs were primarily allocated electively within the donor region (according to urgency and waiting time). Afterwards, all patients in Germany eligible for heart transplants were registered in a national waiting list. With the exception of high-urgency patients that are approved by an audit committee, waiting time has become the major criteria for allocation. In this study, we investigated the impact of the new allocation system on economic aspects as on clinical results. METHODS One year in the new allocation system (NA) was compared to the previous year in the old allocation system (OA) regarding explantation/transportation distance, costs, ischemia time and clinical outcome. All explantations performed by our institution within Germany were evaluated. RESULTS The number of transplantations and the spectrum was similar between the two time periods (NA vs. OA: 61 vs. 57 overall). Eighty-two percent of these explanted organs were transplanted within the donor region in the OA time period, but only 37 % in the NA period. This resulted in higher transportation distances (NA: 441 +/- 177 km vs. OA: 179 +/- 118 km), higher transportation cost (NA: EUR 4,472 +/- 2,858 per explantation vs. OA: EUR 1,858 +/- 2,293 explantation, p = 0.001), and therefore longer ischemia times in the NA period (NA: 264 +/- 56 min: OA: 208 + 61 min, p = 0.001). Perioperative results and survival after a mean clinical follow-up of 21 +/- 8 (OA) and 11 +/- 5 (NA) months were comparable (86 % vs. 87 % (p = 0.93). CONCLUSION Transportation distance, costs for explantation and ischemia time increased significantly with the NA period. While the clinical short-term outcome proved to be comparable, we cannot yet judge the long-term impact of the prolonged ischemia time on the development of chronic rejection.

To determine whether on-clamp partial nephrectomy (ON-PN) has any significant impact on long-term renal function in a two kidney model.From November 1999 to July 2013, 607 patients underwent PN at our institution. After excluding patients with solitary kidneys, multiple renal masses, and follow-up less than 90 days, 331 remained. Patient demographics were assessed, as was renal function based on pre- and postoperative mercaptoacetyltriglycine (MAG-3) renal scans and change in estimated glomerular filtration rate (eGFR) using the preoperative and most recent recorded creatinine levels.There were a total of 236 patients who underwent ON-PN and 95 who underwent off-clamp PN (OFF-PN) during the study period. The longest follow-up was 12.6 years with mean follow-up of 3 years. Mean ischemia time of patients undergoing ON-PN was 25 minutes (range 8-63 min). No differences were noted between the ON-PN and OFF-PN cohorts with respect to estimated change in eGFR (ON-PN: -6.07 mL/min/1.73 m(2) vs OFF-PN: -6.00 mL/min/1.73 m(2), P=0.69). No differences were noted in the % change in the MAG-3 renal scans (ON-PN: -0.77% vs OFF-PN: -1.1%, P=0.94). A post hoc sensitivity analysis of the same two variables stratified by age revealed no differences in change in estimated GFR or % change in differential function on renal scan.In the two kidney model, ischemia does not appear to affect long-term renal function outcomes after PN. These data provide evidence that ON-PN is perfectly acceptable in the appropriately selected patient with two kidneys.

Drainages in primary knee arthroplasty remain unclear. Our aim is to analyze variables that may affect bleeding in knee arthroplasty (age, drained volume, and ischemia time). We included 188 knee arthroplasties, divided into three groups: conventional approach for total knee arthroplasty (TKA), minimally invasive total knee arthroplasty (MIS), and unicompartmental knee arthroplasty (UNI). Main variables analyzed for the present study were age, drained volume, and ischemia time. Other recorded variables were operated knee, pre- and postoperative hematocrit, diagnosis, comorbidities, and transfusions required. No relationship between age and drained volume was observed. However, patients younger than 70 years presented a major rate of survival curve bleeding. A statistically significant difference was found between drained volume in UNI in contrast to TKA and MIS. There was a significant relationship between time and bleeding at 24 hours postoperative, observing that the greater the bleeding, the longer it would keep bleeding (log-rank, p