Effect of the Duration of Deep Hypothermic Circulatory Arrest on the Neurodevelopmental Outcomes in Children Undergoing Cardiac Surgery.

Background/Objectives: Deep hypothermic circulatory arrest (DHCA) is safe, but subtle neurodevelopmental deficits may persist far beyond the perioperative period. We aimed to investigate the relationship between DHCA duration and neurodevelopmental outcomes in young children undergoing cardiac surgery with DHCA. Methods: Children aged < 42 months, including neonates who underwent cardiac surgery using DHCA without regional perfusion techniques, were included as the DHCA group. Children in the same age range who underwent cardiac surgery without DHCA were included as the control group. All enrolled patients underwent neurodevelopmental assessment using the Bayley Scales of Infant and Toddler Development (BSTID) by a trained pediatrician, and 17 DHCA patients and 6 control patients completed the BSTID assessment. Results: Both groups showed no significant preoperative, operative, or postoperative differences. Adjusted multivariable analysis revealed that prematurity and age at assessment were significant changing predictors of each of the BSTID components (p < 0.001), except for the gross motor component, where only age at assessment was a significant adjusting predictor. Longer DHCA was associated with lower fine and gross motor BSTID components; however, the association was not statistically significant (p = 0.06). Conclusions: Long-duration DHCA without regional perfusion techniques may be associated with less optimal neurodevelopmental outcomes.

Efficient Desulfurizer Recycling during Spent Lead-Acid Batteries Paste Disposal by Zero-Carbon Precursor Hypothermic Smelting.

Recycling of spent lead-acid batteries (LABs) is extremely urgent in view of environmental protection and resources reuse. The current challenge is to reduce high consumption of chemical reagents. Herein, a closed-loop spent LABs paste (SLBP) recovery strategy is demonstrated through Na2MoO4 consumption-regeneration-reuse. Experimental and DFT calculations verify that MoO4 2- competes Pb/Ca ions and weakens the metal-oxygen bond of PbSO4/CaSO4.2H2O in SLBP, facilitating PbMoO4/CaMoO4 formation and 99.13 wt% of SO4 2- elimination. Pb of 99.97 wt% is obtained as zero-carbon precursors (PbO2 and PbMoO4) by green leaching coupled with re-crystallization. The regeneration of Na2MoO4 is realized at 600 ℃ using LABs polypropylene shells and NaOH as reagents. Compared with the traditional smelting technologies, the temperature is reduced from ＞1000 to 600 °C. The extraction of Na2MoO4 require only water, and satisfactory re-used desulfurization efficiency (98.67 wt%) is achieved. For the residual Na2MoO4 after first SLBP desulfurization, the desulfurization efficiency remains above 97.36 wt% after adding fresh reagents for two running cycles. The new principle enables the reuse of 99.83 wt% of Na2MoO4 and the recycling of 95.27 wt% of Pb without generating wastewater and slags. The techno-economic analysis indicates this strategy is efficient, economical, and environmentally-friendly.

Neurocognitive Dysfunction After Short (<20 Minutes) Duration Hypothermic Circulatory Arrest.

BACKGROUND: It has long been held that the safe duration of hypothermic circulatory arrest (HCA) is at least 25-30 minutes. However, this is based primarily on clinical outcomes research and has not been systematically investigated using more sensitive brain imaging and neurocognitive assessments. METHODS: This exploratory sub-study of the randomized GOT ICE trial, which compared outcomes for deep versus moderate hypothermia during arch surgery, investigated the frequency of neurocognitive and structural and functional magnetic resonance imaging (MRI) deficits with short (<20 minutes) duration HCA. Neurocognitive deficit was defined as >1 standard deviation decline in >1 of 5 cognitive domains on neurocognitive testing. RESULTS: Of 228 GOT ICE patients with complete 4-week cognitive data, 74.6% (n=170/228) had HCA durations <20 minutes, including 59 randomized to deep (<20.0°C), 55 low-moderate (20.1-24.0°C), and 56 high-moderate (24.1-28.0°C) hypothermia. Of these, cognitive deficit was detected 4-weeks post-surgery in ∼40% of patients in all 3 groups [deep: 22/59 (37.3%); low-moderate: 23/55 (41.8%); high-moderate: 24/56 (42.9%)]. Furthermore, in a subset of patients with complete MRI data (n=43), baseline to 4-week post-surgery right frontal lobe functional connectivity change was inversely associated with HCA duration (range 8-17 minutes; p-FWE<0.01). CONCLUSIONS: Even short durations of HCA result in cognitive deficits in ∼40% of patients, independent of systemic hypothermia temperature. HCA duration was inversely associated with frontal lobe functional MRI connectivity, suggesting this brain region may be preferentially sensitive to HCA. Surgeons should be aware that even short durations of HCA may not provide complete neuroprotection following aortic arch surgery.

Remimazolam ameliorates postoperative cognitive dysfunction after deep hypothermic circulatory arrest through HMGB1-TLR4-NF-κB pathway.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a complication of deep hypothermic circulatory arrest (DHCA). Various amounts of neurologic dysfunctions have been shown after DHCA, which has often been attributed to systemic inflammatory response syndrome and cerebral ischemia/reperfusion injury. Remimazolam is one of the commonly used anesthetic drugs with protective actions against inflammatory diseases, such as sepsis and cerebral ischemia/reperfusion injury. Here, we determined the protective effect and potential mechanism of action of remimazolam against neuronal damage after DHCA. METHODS: A rat model of DHCA was established, and a gradient dosage of remimazolam was administered during cardiopulmonary bypass (CPB). The cognitive function of rats was evaluated by Morris water maze. Hematoxylin and eosin and TUNEL staining were performed to assess hippocampus tissue injury and neuronal apoptosis. Inflammatory cytokines concentration were analyzed by enzyme-linked immunosorbent assay. The protein expression was analyzed using automated electrophoresis western analysis and immunohistochemical analysis. RESULTS: The appropriate dosage of remimazolam reduced histologic injury, neuronal apoptosis, microglia activation, and secondary inflammatory cascades, as well as the downregulation of the expression of the HMGB1-TLR4-NF-κB pathway after DHCA, improved the memory and learning abilities in DHCA rats. Further, administration of a TLR4 antagonist TAK-242 had a similar effect to remimazolam, while the TLR4 agonist LPS attenuated the effect of remimazolam. CONCLUSIONS: Remimazolam could ameliorate POCD after DHCA through the HMGB1-TLR4-NF-κB signaling pathway.

Assessment of liver graft quality during hypothermic oxygenated perfusion: the first international validation study.

BACKGROUND AND AIM: While it is currently assumed that liver assessment is only possible during normothermic machine perfusion (NMP), there is uncertainty regarding a reliable and quick prediction of graft injury during ex situ hypothermic oxygenated perfusion (HOPE). We therefore intended to test, in an international liver transplant cohort, recently described mitochondrial injury biomarkers measured during HOPE before liver transplantation. STUDY DESIGN: Perfusate samples of human livers from 10 centers in 7 countries with HOPE-experience were analyzed for released mitochondrial compounds, i.e. flavin mononucleotide (FMN), NADH, purine derivates and inflammatory markers. Perfusate FMN was correlated with graft loss due to primary non-function or symptomatic non-anastomotic biliary strictures (NAS), and kidney failure, as well as liver injury after transplantation. Livers deemed unsuitable for transplantation served as negative control. RESULTS: We collected 473 perfusate samples of human DCD (n=315) and DBD livers (n=158). Fluorometric assessment of FMN in perfusate was validated by mass spectrometry (R=0.7011,p<0.0001). Graft loss due to primary non-function or cholangiopathy was predicted by perfusate FMN values (c-statistic mass spectrometry 0.8418 (95%CI 0.7466-0.9370,p<0.0001), c-statistic fluorometry 0.7733 (95%CI 0.7006-0.8461,p<0.0001). Perfusate FMN values were also significantly correlated with symptomatic NAS and kidney failure, and superior in prediction of graft loss when compared to conventional scores derived from donor and recipient parameters, such as the donor risk index and the balance of risk score. Mitochondrial FMN values in liver tissues of non-utilized livers were low, and inversely correlated to high perfusate FMN values and purine metabolite release. CONCLUSIONS: This first international study validates the predictive value of the mitochondrial co-factor FMN, released from complex I during HOPE, and may therefore contribute to a better risk stratification of injured livers before implantation. IMPACT AND IMPLICATIONS: Analysis of 473 perfusates, collected from 10 international centers during hypothermic oxygenated perfusion (HOPE), revealed that mitochondria derived flavin mononucleotide (FMN) values in perfusate is predictive for graft loss, cholangiopathy, and kidney failure after liver transplantation. This result is of high clinical relevance, as recognition of graft quality is urgently needed to improve the safe utilization of marginal livers. Ex-situ machine perfusion approaches, such as HOPE, are therefore likely to increase the number of useable liver grafts.

Matched pair analysis of the effect of longer hypothermic machine perfusion time on kidney transplant outcomes.

BACKGROUND: Hypothermic machine perfusion (HMP) has demonstrated benefits in terms of early kidney transplant function compared to static cold storage. While longer preservation times have shown detrimental effects, a previous paired study indicated that longer pump times (the second kidney in a pair) might lead to improved outcomes. AIM: To revisit the prior paired study's somewhat unexpected results by reviewing our program's experience. METHODS: A total of 61 pairs of transplant recipients who received kidneys from the same donor (2012-2021) were analyzed. Patients were divided into two groups depending on whether they were transplanted first (K1) or second (K2). Therefore, the patients in each pair had identical donor characteristics, except for time on the pump. Statistical analyses included Kaplan-Meyer analysis and paired tests, including McNemar's test, student's paired t-test, or Wilcoxon's test, as appropriate. RESULTS: The two groups of recipients had similar demographics (age, body mass index, diabetes, time on dialysis, sensitization and retransplants). Cold ischemic times for K1 and K2 were 8.9 (95%CI: 7.9, 9.8) and 14.7 hours (13.7, 15.8) (P < 0.0001), respectively. Overall, K2 had a higher rate of freedom from biopsy-proven acute rejection at 1 year (P = 0.015). Delayed graft function was less common in K2, 12/61 (20%) than in K1, 20/61 (33%) (P = 0.046). Finally, K2 showed a higher graft survival than K1 (P = 0.023). CONCLUSION: Our results agree with a previous study that suggested possible advantages to longer pump times. Both studies should encourage further research into HMP's potential anti-inflammatory effect.

Long-term hypothermic storage of oocytes of the European common frog Rana temporaria at various pressure regimes in gas mixtures based on oxygen, carbon monoxide, and nitrous oxide.

In recent years, the challenge of preserving amphibian biodiversity has increasingly been addressed through technologies for the short-term storage of unfertilized spawn at low positive temperatures. Previously the possibility of using a 6.5 atm gaseous mixture of carbon monoxide and oxygen for prolonged hypothermic preservation of unfertilized oocytes for more than 4 days was shown. This study aimed to investigate the viability of oocytes R. temporaria preserved under conditions of hypothermia at 2.5, 3 and 6.5 excess atm pressure in the various gas mixture compositions (CO, N2O, O2) and pure oxygen. The use of pressure up to 3 excess atmospheres was significantly beneficial compared to 6.5 atm at the 7 days storage period. The results indicate that oxygen pressure is a critical factor in maintaining oocyte viability. Admixing CO or N2O to oxygen reduced variability in the results but did not significantly affect the measured indicators (fertilization, hatching) in the experimental groups. The composition CO + O2 (0.5/3.5 ratio, 3 excess atm) reliably extended the shelf life of viable oocytes, indistinguishable from native controls by fertilization and hatching rates, to 4 days. After 7 days, oocytes exhibited fertilization and hatching rates that were 79 % and 48 % compared to native control. Reducing the pressure of the preserving gas mixture to 3 atm, as utilized in this study, simplifies the practical implementation of gas preservation technology for maintaining endangered amphibian species during breeding in laboratory conditions.

Zwitterionic-hydrogel-based sensing system enables real-time ROS monitoring for ultra-long hypothermic cell preservation.

Hypothermic preservation (HP) is highly desired for the maintenance of the viability of living cell specimens, e.g. rare cells in whole-blood samples or therapeutic cells, in an unfrozen state. However, the extension of the viable preservation time is a challenge because of the multiple injuries suffered by hypothermically preserved cells. Here, based on a dynamic bond crosslinked zwitterionic hydrogel, we established a sensing preservation system that could monitor the levels of reactive oxygen species (ROS) via real-time electronic signals and intelligent control of antioxidant addition, to completely prevent an excess of ROS in the whole-cell specimen. Furthermore, the hydrogel-based system can counter the extracellular-matrix-loss-induced anoikis of living cells. Based on the design aimed at affording protection against two primary HP injuries (i.e. ROS overproduction and anoikis) to cells, this system extended the preservation time of cell specimens under refrigerated conditions to 24 days. After preservation, the use of a mild cell retrieval process guaranteed the activity of the preserved living cells. This work not only possesses the potential to facilitate intelligent cell-based clinical applications, but also paves the way for the preparation of living materials that can host programmed cells with long-term survival. STATEMENT OF SIGNIFICANCE: An intelligent system based on a zwitterionic sensing hydrogel is established, which can afford ultra-long hypothermic cell-preservation times of up to 24 days. The system enables the real-time monitoring of ROS overproduction and intelligent antioxidant addition, because of the merging of the smart hydrogel with a computer intelligent detection and control system. Furthermore, the automatic addition of an antioxidant according to the ROS-signal changes produced by the ZBA hydrogel effectively prevented HP lesions, including ROS over-production and ECM loss, in the preserved living cells. Subsequently, the system could also be gently dissociated, to retrieve the preserved cells. This work provides a solution for the real-time monitoring and long-term HP of living specimens, which holds the promise of benefiting cell-based medicine and the development of genetically programmed cell-based living materials.

The optimal degree of core temperature for hypothermic circulatory arrest in complex aortic arch surgery: results from 1310 patients.

OBJECTIVES: The optimal core temperature for hypothermic circulatory arrest during aortic arch surgery remains contentious. This study aims to evaluate patient outcomes under various temperatures within a large single-centre cohort. METHODS: Between 2010 and 2018, patients diagnosed with type A aortic dissection underwent total arch replacement at Fuwai Hospital were enrolled. They were categorized into 4 groups: deep hypothermia group, low-moderate hypothermia group, high-moderate hypothermia group and mild hypothermia group. Clinical data were analysed to ascertain differences between the groups. RESULTS: A total of 1310 patients were included in this cohort. Operative mortality stood at 6.9% (90/1310), with a higher incidence observed in the deep hypothermia group [29 (12.9%); 35 (6.9%); 21 (4.8%); 5 (3.4%); all adjusted P < 0.05]. Overall 10-year survival was 80.3%. Long-term outcomes did not significantly differ among the groups. Multivariable logistic analysis revealed a protective effect of higher core temperature on operative mortality (odds ratio 0.848, 95% confidence interval 0.766-0.939; P = 0.001). High-moderate hypothermia emerged as an independent protective factor for operative mortality (odds ratio 0.303, 95% confidence interval 0.126-0.727; P = 0.007). Multivariable Cox analysis did not detect an effect of hypothermic circulatory arrest on long-term survival (all P > 0.05). CONCLUSIONS: High-moderate hypothermia (24.1-28°C) offers the most effective protection against surgical mortality and is therefore recommended. Different hypothermic circulatory arrest temperatures do not influence long-term survival or quality of life.

Effects of temperature on transient neurologic dysfunction after total arch replacement.

OBJECTIVES: The relationship between cooling status during aortic surgery with hypothermic circulatory arrest and postoperative neurologic dysfunction remains unknown. In the present study, we evaluated the effect of cooling status on transient neurologic dysfunction after total arch replacement. METHODS: We studied patients who underwent elective total arch replacement with hypothermic circulatory arrest and antegrade selective cerebral perfusion from December 2011 to January 2021. Changes in tympanic temperature trends recorded during surgery were plotted. Several parameters, including the nadir temperature, cooling speed, and degree of cooling (cooling area, or the area under the curve of inverted temperature trends from cooling to rewarming as calculated by the integral method), were analyzed. The relationships between these variables and transient neurologic dysfunction were evaluated. RESULTS: Transient neurologic dysfunction was observed in 33 (14.5%) of the 228 included patients. In the transient neurologic dysfunction group, the cooling area was larger (2417.3 vs. 1920.8 °C min; P < 0.001) and the cooling speed was higher (0.68 vs. 0.51 °C/min; P < 0.001) than in the non-transient neurologic dysfunction group. A multivariate logistic model revealed that both the cooling area (odds ratio = 1.13 per 100 °C min; P < 0.001) and cooling speed (odds ratio = 3.69 per °C/min; P = 0.041) were independent risk factors for transient neurologic dysfunction. CONCLUSIONS: Both the cooling area, which indicates the degree of cooling, and cooling speed had significant relationships with transient neurologic dysfunction after total arch replacement. Together, these findings indicate that overcooling and rapid cooling may contribute to brain injury.

Giant unruptured middle cerebral artery aneurysm revealed by intracranial hypertension: is a systematic decompressive hemicraniotomy mandatory?

Our study aimed to evaluate the postoperative outcome of patients with unruptured giant middle cerebral artery (MCA) aneurysm revealed by intracranial hypertension associated to midline brain shift. From 2012 to 2022, among the 954 patients treated by a microsurgical procedure for an intracranial aneurysm, our study included 9 consecutive patients with giant MCA aneurysm associated to intracranial hypertension with a midline brain shift. Deep hypothermic circulatory flow reduction (DHCFR) with vascular reconstruction was performed in 4 patients and cerebral revascularization with aneurysm trapping was the therapeutic strategy in 5 patients. Early (< 7 days) and long term clinical and radiological monitoring was done. Good functional outcome was considered as mRS score ≤ 2 at 3 months. The mean age at treatment was 44 yo (ranged from 17 to 70 yo). The mean maximal diameter of the aneurysm was 49 mm (ranged from 33 to 70 mm). The mean midline brain shift was 8.6 mm (ranged from 5 to 13 mm). Distal MCA territory hypoperfusion was noted in 6 patients. Diffuse postoperative cerebral edema occurred in the 9 patients with a mean delay of 59 h and conducted to a postoperative neurological deterioration in 7 of them. Postoperative death was noted in 3 patients. Among the 6 survivors, early postoperative decompressive hemicraniotomy was required in 4 patients. Good functional outcome was noted in 4 patients. Complete aneurysm occlusion was noted in each patient at last follow-up. We suggest to discuss a systematic decompressive hemicraniotomy at the end of the surgical procedure and/or a partial temporal lobe resection at its beginning to reduce the consequences of the edema reaction and to improve the postoperative outcome of this specific subgroup of patients. A better intraoperative assessment of the blood flow might also reduce the occurrence of the reperfusion syndrome.

Cerebral Protection With Deep Hypothermic Circulatory Arrest During Total Arch Replacement Using the Arch-First Technique for Acute Aortic Dissection.

OBJECTIVES: Stroke remains a serious complication after total arch replacement (TAR). To prevent this, deep hypothermia is commonly employed during TAR. We evaluated the effectiveness of cerebral protection using deep hypothermic circulatory arrest (DHCA) during TAR with the arch-first technique, focusing particularly on patients with acute aortic dissection (AAD). METHODS: This retrospective study included 109 consecutive patients with AAD who underwent emergency TAR using the arch-first technique under DHCA, and 147 patients with non-ruptured aneurysm who underwent scheduled TAR using the same technique between October 2009 and July 2022. We reviewed these patients for major adverse events, including stroke and 30-day mortality after surgery. We also analyzed the impact of clinical variables and anatomical features on the occurrence of newly developed stroke after TAR in patients with AAD. RESULTS: A newly developed stroke after TAR occurred in 11 (10.1%) patients with AAD. These were attributed to embolism in eight patients, malperfusion in two patients (including one who had been comatose), and low output syndrome in one patient. A stroke occurred in 3 (2.0%) patients with aneurysm, all due to embolism (P = 0.005). The DHCA time was 37 ± 7 minutes for patients with AAD and 36 ± 6 minutes for patients with aneurysm (P = 0.122). The 30-day mortality rate was 10 (9.2%) for patients with AAD and 2 (1.4%) for patients with aneurysm (P = 0.003). In our multivariable analysis, arch vessel dissection with a patent false lumen (double-barreled dissection) was the only significant predictor of newly developed stroke after TAR for AAD (odds ratio, 33.02; P < 0.001). CONCLUSIONS: Patients with aneurysm undergoing TAR using the arch-first technique under DHCA experienced significantly better outcomes, in terms of newly developed stroke and 30-day mortality, than those with AAD. Cerebral protection with DHCA during TAR using the arch-first technique continues to be a viable option. Newly developed stroke in patients undergoing TAR for AAD appears to be associated with air emboli deriving from the residual dissection with a patent false lumen in the repaired arch vessels.

Cerebral Protection Strategies in Aortic Arch Surgery-Past Developments, Current Evidence, and Future Innovation.

Surgery of the aortic arch remains a complex procedure, with neurological events such as stroke remaining its most dreaded complications. Changes in surgical technique and the continuous innovation in neuroprotective strategies have led to a significant decrease in cerebral and spinal events. Different modes of cerebral perfusion, varying grades of hypothermia, and a number of pharmacological strategies all aim to reduce hypoxic and ischemic cerebral injury, yet there is no evidence indicating the clear superiority of one method over another. While surgical results continue to improve, novel hybrid and interventional techniques are just entering the stage and the question of optimal neuroprotection remains up to date. Within this perspective statement, we want to shed light on the current evidence and controversies of cerebral protection in aortic arch surgery, as well as what is on the horizon in this fast-evolving field. We further present our institutional approach as a large tertiary aortic reference center.

Evaluation of end-organ protection in newborns and infants after surgery of aortic arch hypoplasia: A prospective randomized study.

INTRODUCTION: Surgical repair of aortic arch hypoplasia in children requires a "dry" surgical field with reliable end-organ protection. Perfusion strategies commonly involve deep hypothermic circulatory arrest (DHCA) and variations of the continuous perfusion techniques, such as selective antegrade cerebral perfusion (SACP) and full-flow perfusion with double aortic cannulation (DAC). We aimed to evaluate the end-organ protection in the surgery of aortic arch hypoplasia in newborns and infants using DHCA and DAC. MATERIALS AND METHODS: 66 newborns and infants with aortic arch hypoplasia and biventricular anatomy were enrolled in this prospective study. Patients were randomly assigned into two groups according to the perfusion strategy - DHCA (n = 33); and DAC (n = 33). Primary endpoint: acute kidney injury (AKI), graded according to the KDIGO score. Secondary endpoints: neurological sequelae (pre- and postoperative MRI), in-hospital mortality. RESULTS: The lowest temperature was 32 (28; 34)°Ð¡ in the DAC group and 23 (20; 25)°Ð¡ in the DHCA group. The patients with DAC had lower incidence of AKI (6 patients (18.2%) versus 19 patients (57.6%); p = .017). In the multivariate analysis, the inotropic index at 48 h was identified as a risk factor, increasing the risk of AKI by 4%. The DHCA group was associated with a 3.8-fold increase in the risk of AKI. There was no difference in hospital mortality between the DAC and DHCA groups (1 patient (3%) versus 3 patients (9.1%); p = .61). Neurological sequelae by MRI scan were observed in 18 patients (54.5%) in the DHCA group compared to 5 patients (15.15%) in the DAC group (p = .026). The only risk factor identified in the multivariate analysis for neurological lesions on MRI scan was the DHCA group, which increased the risk by 8.8 times. CONCLUSIONS: Surgical reconstruction of the aortic arch hypoplasia using the method of full-body perfusion reduces the incidence of neurological lesions and renal complications requiring renal replacement therapy compared with the deep hypothermic circulatory arrest in neonates and infants.

Simultaneous liver-kidney transplantation: future perspective.

BACKGROUND: The aims of this narrative review were (i) to describe the current indications of SLKT, (ii) to report evolution of SLKT activity, (iii) to report the outcomes of SLKT, (iv) to explain the immune-protective effect of liver transplant on kidney transplant, (v) to explain the interest of delay kidney transplantation, using hypothermic machine perfusion (HMP), (vi) to report kidney after liver transplantation (KALT) indications and (vii) to describe the value of the increase in the use of extended criteria donors (ECD) and particular controlled donation after circulatory death (cDCD) transplant, thanks to the development of new organ preservation strategies. METHOD: Electronic databases were screened using the keywords "Simultaneous", "Combined", "kidney transplantation" and "liver transplantation". The methodological and clinical heterogeneity of the included studies meant that meta-analysis was inappropriate. RESULTS:  A total of 1,917 publications were identified in the literature search. Two reviewers screened all study abstracts independently and 1,107 of these were excluded. Thus, a total of 79 full text articles were assessed for eligibility. Of these, 21 were excluded. In total, 58 studies were included in this systematic review. CONCLUSIONS:  Simultaneous liver-kidney transplantation has made a significant contribution for patients with dual-organ disease. The optimization of indication and selection of SLKT patients will reduce futile transplantation. Moreover, increasing the use of transplants from extended criteria donors, in particular cDCD, should be encouraged, thanks to the development of new modalities of organ preservation.

Long-term outcomes after hypothermic oxygenated machine perfusion and transplantation of 1,202 donor livers in a real-world setting (HOPE-REAL study).

BACKGROUND & AIMS: Despite strong evidence for improved preservation of donor livers by machine perfusion, longer post-transplant follow-up data are urgently needed in an unselected patient population. We aimed to assess long-term outcomes after transplantation of hypothermic oxygenated machine perfusion (HOPE)-treated donor livers based on real-world data (i.e., IDEAL-D stage 4). METHODS: In this international, multicentre, observational cohort study, we collected data from adult recipients of HOPE-treated livers transplanted between January 2012 and December 2021. Analyses were stratified by donation after brain death (DBD) and donation after circulatory death (DCD), sub-divided by their respective risk categories. The primary outcome was death-censored graft survival. Secondary outcomes included the incidence of primary non-function (PNF) and ischaemic cholangiopathy (IC). RESULTS: We report on 1,202 liver transplantations (64% DBD) performed at 22 European centres. For DBD, a total number of 99 benchmark (8%), 176 standard (15%), and 493 extended-criteria (41%) cases were included. For DCD, 117 transplants were classified as low risk (10%), 186 as high risk (16%), and 131 as futile (11%), with significant risk profile variations among centres. Actuarial 1-, 3-, and 5-year death-censored graft survival rates for DBD and DCD livers were 95%, 92%, and 91%, vs. 92%, 87%, and 81%, respectively (log-rank p = 0.003). Within DBD and DCD strata, death-censored graft survival was similar among risk groups (log-rank p = 0.26, p = 0.99). Graft loss due to PNF or IC was 2.3% and 0.4% (DBD), and 5% and 4.1% (DCD). CONCLUSIONS: This study shows excellent 5-year survival after transplantation of HOPE-treated DBD and DCD livers with low rates of graft loss due to PNF or IC, irrespective of their individual risk profile. HOPE treatment has now reached IDEAL-D stage 4, which further supports its implementation in routine clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05520320. IMPACT AND IMPLICATIONS: This study demonstrates the excellent long-term performance of hypothermic oxygenated machine perfusion (HOPE) treatment of donation after circulatory and donation after brain death liver grafts irrespective of their individual risk profile in a real-world setting, outside the evaluation of randomised-controlled trials. While previous studies have established safety, feasibility, and efficacy against the current standard, according to the IDEAL-D evaluation framework, HOPE treatment has now reached the final IDEAL-D stage 4, which further supports its implementation in routine clinical practice.

Donor Conditioning and Organ Pre-Treatment Prior to Kidney Transplantation: Reappraisal of the Available Clinical Evidence.

Therapeutic measures aimed at optimising organ function prior to transplantation-whether by conditioning the donor after determination of brain death or by improving organ preservation after kidney removal-have the potential to enhance outcomes after transplantation. The particular advantage is that, unlike any optimised immunosuppressive therapy, a favourable effect can be achieved without side effects for the organ recipient. In recent years, several such measures have been tested in controlled clinical trials on large patient cohorts following kidney transplantation. Hypothermic pulsatile machine perfusion, in particular, has become the focus of interest, but interventions in the donor prior to organ removal, such as the administration of low-dose dopamine until the start of cold perfusion as an example of conditioning antioxidant therapy and therapeutic donor hypothermia in the intensive care unit after brain death confirmation, have also significantly reduced the frequency of dialysis after transplantation with far less effort and cost. With regard to benefits for graft survival, the database for all procedures is less clear and controversial. The aim of this review article is to re-evaluate the available clinical evidence from large multicentre controlled trials, which have also significantly influenced later meta-analyses, and to assess the significance for use in routine clinical practice.

[Machine perfusion in transplantation surgery]. / Maschinenperfusion in der Transplantationschirurgie.

The use of machine perfusion in solid organ transplantation has developed tremendously worldwide in recent years. Although the number of randomized controlled trials in the field of organ preservation is still limited, machine perfusion has been shown to be superior to static cold storage of donor organs. Various devices for clinical use with hypothermia or normothermia are already available for most organs. Whether and which perfusion strategy is superior to the others is the subject of current clinical research. This also applies to the further evaluation of possible synergistic effects in the sequential use of the various protocols. The common goal of all dynamic perfusion technologies is to optimize organ preservation between removal and transplantation. By testing the quality of marginal donor organs prior to transplantation, it should also be possible to use these organs without exposing the patient to increased risk. This can lead to a significant expansion of the donor pool. This is particularly important in Germany, where there is an ongoing shortage of organs and restrictive legislation regarding the expansion of the donor pool. Furthermore, the perfusion technology offers the possibility to serve as a platform for other ex situ and in situ therapies on isolated organs. In addition to the conditioning of pre-damaged organs for transplantation, this could lead to further applications in the context of targeted organ therapies and also to improved transplant logistics in the future.

Comparative study of neonatal hypothermia and associated factors among neonates in rural and urban areas of the Shebadino Woreda, Sidama region, Southern Ethiopia: a community-based comparative cross-sectional study.

BACKGROUND: Hypothermia is one of the major causes of newborn death, particularly in low-income nations. This was due to poor thermal care in most of the rural communities. Recent studies show that there was a prevalence discrepancy between urban and rural communities where economic, educational, and life standard differences exist. Therefore, this study aimed to assess the prevalence and factors associated with neonatal hypothermia among neonates in rural and urban areas of the Shebadino woreda, Sidama region, Ethiopia. METHOD: A comparative community-based cross-sectional study was performed on 682 neonates in the Shebadino Woreda, Sidama Region, southern Ethiopia, in 2023. A multistage sampling technique was used, and the collected data were manually cleaned, coded, and entered into Epi Data version 4.6 before being exported to SPSS version 26 software for analysis. Variables with a p-value < 0.25 in the bivariate logistic regression were further analyzed using multivariable logistic regression. The odds ratio (OR) with 95% CI was used as a measure of association, and variables that had a p-value less than 0.05 in the multivariable logistic regression were considered significantly associated variables. RESULTS: The overall prevalence of neonatal hypothermia in this study was 51.8% (95% CI: 47.2%-56.3%). It was greater among rural neonates (55.1%) than among urban neonates (48.6%). Bathing before 24 h. (AOR = 3.64, 95% CI: 1.39, 7.16), Placing a cold object near babies' head (AOR = 2.97, 95% CI: 1.75, 5.03), Neonates who were given traditional medication (Amessa) (AOR = 1.83% CI; 1.04-3.20) and, not separated humans and animals house (AOR = 1.75, 95%, 1.05-2.91) were significantly associated with neonatal hypothermia in rural, while Night time delivery (AOR = 1.81, CI: 1.01-5.62), Neonates who were given traditional medication (Amessa) (AOR = 3.11% CI; 1.85-5.21), and Placing a cold object near babies' head (AOR = 2.40, 95% CI: 1.37, 3.29 were significantly associated with neonatal hypothermia among urban neonates. CONCLUSION: The Prevalence of neonatal hypothermia in the study area was relatively greater in rural areas than in urban areas. Cost-effective thermal care such as separating humans from animal houses, teaching not to put cold objects near babies, giving special care to newborns for those delivered from women with medical problems, and giving priority to those delivered at night, is needed.