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Journal of Hepatology Aug 2023Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ availability. Ischemia-free organ transplantation is a novel approach designed to avoid IRI, with the potential to improve outcomes.
METHODS
In this randomized-controlled clinical trial, recipients of livers from donors after brain death were randomly assigned to receive either an ischemia-free or a 'conventional' transplant. The primary endpoint was the incidence of early allograft dysfunction. Secondary endpoints included complications related to graft IRI.
RESULTS
Out of 68 randomized patients, 65 underwent transplants and were included in the analysis. 32 patients received ischemia-free liver transplantation (IFLT), and 33 received conventional liver transplantation (CLT). Early allograft dysfunction occurred in two recipients (6%) randomized to IFLT and in eight (24%) randomized to CLT (difference -18%; 95% CI -35% to -1%; p = 0.044). Post-reperfusion syndrome occurred in three recipients (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference -54%; 95% CI -74% to -35%; p <0.001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in two recipients (8%) randomized to IFLT and in nine (36%) randomized to CLT (difference, -28%; 95% CI -50% to -7%; p = 0.014). The comprehensive complication index at 1 year after transplantation was 30.48 (95% CI 23.25-37.71) in the IFLT group vs. 42.14 (95% CI 35.01-49.26) in the CLT group (difference -11.66; 95% CI -21.81 to -1.51; p = 0.025).
CONCLUSIONS
Among patients with end-stage liver disease, IFLT significantly reduced complications related to IRI compared to a conventional approach.
CLINICAL TRIAL REGISTRATION
chictr.org. ChiCTR1900021158.
IMPACT AND IMPLICATIONS
Ischemia-reperfusion injury has thus far been considered as an inevitable event in organ transplantation, compromising outcomes and limiting organ availability. Ischemia-free liver transplantation is a novel approach of transplanting donor livers without interruption of blood supply. We showed that in patients with end-stage liver disease, ischemia-free liver transplantation, compared with a conventional approach, led to reduced complications related to ischemia-reperfusion injury in this randomized trial. This new approach is expected to change the current practice in organ transplantation, improving transplant outcomes, increasing organ utilization, while providing a clinical model to delineate the impact of organ injury on alloimmunity.
Topics: Humans; Liver Transplantation; End Stage Liver Disease; Ischemia; Liver; Reperfusion Injury; Perfusion; Organ Preservation
PubMed: 37086919
DOI: 10.1016/j.jhep.2023.04.010 -
JAMA Network Open Jan 2024Assessing clinical tumor response following completion of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer is paramount to select patients... (Randomized Controlled Trial)
Randomized Controlled Trial
Organ Preservation and Survival by Clinical Response Grade in Patients With Rectal Cancer Treated With Total Neoadjuvant Therapy: A Secondary Analysis of the OPRA Randomized Clinical Trial.
IMPORTANCE
Assessing clinical tumor response following completion of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer is paramount to select patients for watch-and-wait treatment.
OBJECTIVE
To assess organ preservation (OP) and oncologic outcomes according to clinical tumor response grade.
DESIGN, SETTING, AND PARTICIPANTS
This was secondary analysis of the Organ Preservation in Patients with Rectal Adenocarcinoma trial, a phase 2, nonblinded, multicenter, randomized clinical trial. Randomization occurred between April 2014 and March 2020. Eligible participants included patients with stage II or III rectal adenocarcinoma. Data analysis occurred from March 2022 to July 2023.
INTERVENTION
Patients were randomized to induction chemotherapy followed by chemoradiation or chemoradiation followed by consolidation chemotherapy. Tumor response was assessed 8 (±4) weeks after TNT by digital rectal examination and endoscopy and categorized by clinical tumor response grade. A 3-tier grading schema that stratifies clinical tumor response into clinical complete response (CCR), near complete response (NCR), and incomplete clinical response (ICR) was devised to maximize patient eligibility for OP.
MAIN OUTCOMES AND MEASURES
OP and survival rates by clinical tumor response grade were analyzed using the Kaplan-Meier method and log-rank test.
RESULTS
There were 304 eligible patients, including 125 patients with a CCR (median [IQR] age, 60.6 [50.4-68.0] years; 76 male [60.8%]), 114 with an NCR (median [IQR] age, 57.6 [49.1-67.9] years; 80 male [70.2%]), and 65 with an ICR (median [IQR] age, 55.5 [47.7-64.2] years; 41 male [63.1%]) based on endoscopic imaging. Age, sex, tumor distance from the anal verge, pathological tumor classification, and clinical nodal classification were similar among the clinical tumor response grades. Median (IQR) follow-up for patients with OP was 4.09 (2.99-4.93) years. The 3-year probability of OP was 77% (95% CI, 70%-85%) for patients with a CCR and 40% (95% CI, 32%-51%) for patients with an NCR (P < .001). Clinical tumor response grade was associated with disease-free survival, local recurrence-free survival, distant metastasis-free survival, and overall survival.
CONCLUSIONS AND RELEVANCE
In this secondary analysis of a randomized clinical trial, most patients with a CCR after TNT achieved OP, with few developing tumor regrowth. Although the probability of tumor regrowth was higher for patients with an NCR compared with patients with a CCR, a significant proportion of patients achieved OP. These findings suggest the 3-tier grading schema can be used to estimate recurrence and survival outcomes in patients with locally advanced rectal cancer who receive TNT.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02008656.
Topics: Humans; Male; Middle Aged; Neoadjuvant Therapy; Organ Preservation; Rectal Neoplasms; Neoplasms, Second Primary; Adenocarcinoma
PubMed: 38194231
DOI: 10.1001/jamanetworkopen.2023.50903 -
International Journal of Gynaecology... Dec 2023Fertility preservation is a growing field in reproductive medicine that may raise ethical questions. Preservation of fertility must be discussed with the patient if...
Fertility preservation is a growing field in reproductive medicine that may raise ethical questions. Preservation of fertility must be discussed with the patient if gonadotoxic treatment is required, whether in the case of benign or malignant pathology, or in the management of transgender identity. As a result, surgery or chemotherapy that has fewer adverse impacts on fertility should be proposed if this does not alter the prognosis of the disease. If the risk of infertility persists, then fertility cryopreservation should be proposed for children and adults of reproductive age. Sperm, oocytes, and gonadal tissue can be cryopreserved for many years. FIGO wishes to emphasize the importance of fertility preservation in the medical and surgical management of patients, and the importance of a specialized, multidisciplinary approach.
Topics: Child; Adult; Humans; Male; Fertility Preservation; Semen; Cryopreservation; Oocytes; Infertility; Neoplasms
PubMed: 37807831
DOI: 10.1002/ijgo.15187 -
Transplant International : Official... 2024
Topics: Humans; Liver Transplantation; Transplants; Perfusion; Organ Preservation; Graft Survival; Liver
PubMed: 38544563
DOI: 10.3389/ti.2024.12853 -
Ugeskrift For Laeger Apr 2024Due to degeneration, homografts were since the 1950s only used strictly for replacement of complex arterial segments and lesions incl. the aortic valve, replacement of... (Review)
Review
Due to degeneration, homografts were since the 1950s only used strictly for replacement of complex arterial segments and lesions incl. the aortic valve, replacement of infected arterial prostheses, and vascular access for patients on haemodialysis. During the 1990s, rate-differentiated freezing methods and anti-crystallization agents proved to prevent crystallisation, and more widespread use with expanded indications incl. coronary and lower limb bypasses began justified by promising midterm results. In 2021, the first Scandinavian homograft biobank was founded in Odense in Denmark. This review summarises the history and the experiences from this biobank.
Topics: Humans; Cryopreservation; Allografts; Blood Vessel Prosthesis; Denmark
PubMed: 38708698
DOI: 10.61409/V07230454 -
Ugeskrift For Laeger Sep 2023Donation after circulatory death (DCD) is practiced in several countries to increase the number of organs for transplantation. This review summarises the key points in a... (Review)
Review
Donation after circulatory death (DCD) is practiced in several countries to increase the number of organs for transplantation. This review summarises the key points in a new protocol which will introduce controlled DCD in Denmark as an option in seriously ill patients, in whom death is inevitable and the criteria for brain death is not met. It includes a no touch period of five minutes following circulatory arrest. Rapid procurement or normothermic regional perfusion may be applied depending on the organs to be transplanted. The introduction of DCD requires thorough training of involved health personnel.
Topics: Humans; Tissue Donors; Organ Preservation; Tissue and Organ Procurement; Cardiovascular System; Denmark
PubMed: 37772648
DOI: No ID Found -
Transfusion Clinique Et Biologique :... May 2024The field of haemovigilance continues to develop, building on more than forty years of international experience. This review considers the current scope and activities... (Review)
Review
The field of haemovigilance continues to develop, building on more than forty years of international experience. This review considers the current scope and activities of haemovigilance around the world and explores aspects of preparation for the advent of new blood products and alternative therapies to transfusion; new tools for data acquisition (including patient- and donor-reported outcomes, and data from 'wearables') and the analysis and communication of haemovigilance results.
Topics: Humans; Blood Safety; Blood Transfusion; Blood Banks; Blood Donors; Forecasting
PubMed: 38460837
DOI: 10.1016/j.tracli.2024.03.001 -
Transplant International : Official... 2023Organ preservation and assessment with machine perfusion (MP) has provided transplant physicians with the ability to evaluate and select grafts suitable for... (Review)
Review
Organ preservation and assessment with machine perfusion (MP) has provided transplant physicians with the ability to evaluate and select grafts suitable for transplantation. Nevertheless, the discard of organs considered too damaged still sustains the imbalance between donor organs supply and demands. Therefore, there is the pressing clinical need for strategies to repair and/or regenerate organs before transplantation, and MP is uniquely positioned to satisfy this need. The systemic administration of mesenchymal stromal cells (MSC) was shown to reduce ischemia-reperfusion injury in pre-clinical organ transplant models but could not be reproduced in clinical transplantation, largely because of inefficient cell delivery. The administration of MSC during MP is one strategy that recently gained much attention as an alternative delivery method to target MSC directly to the donor organ. However, careful reinterpretation of preliminary results reveals that this approach is equally limited by a suboptimal delivery of short-lived MSC to the target organ. In contrast, the use of MSC secretome and/or extracellular vesicles therapy during MP seems to be more efficient in harnessing MSC properties during MP. In this mini review we speculate on the future of the novel niche of organ repair and regeneration before transplantation.
Topics: Humans; Organ Preservation; Organ Transplantation; Regeneration; Perfusion; Mesenchymal Stem Cell Transplantation
PubMed: 38020754
DOI: 10.3389/ti.2023.11947 -
Journal of Assisted Reproduction and... Dec 2023Over the past two decades, the importance of fertility preservation has grown not only in the realm of medical and clinical patient care, but also in the field of basic... (Review)
Review
Over the past two decades, the importance of fertility preservation has grown not only in the realm of medical and clinical patient care, but also in the field of basic and applied research in human reproduction. With advancements in cancer treatments resulting in higher rates of patient survival, it is crucial to consider the quality of life post-cure. Therefore, fertility preservation must be taken into account prior to antitumor treatments, as it can significantly impact a patient's future fertility. For postpubertal patients, gamete cryopreservation is the most commonly employed preservation strategy. However, for prepubertal patients, the situation is more intricate. Presently, ovarian tissue cryopreservation is the standard practice for prepubertal girls, but further scientific evidence is required in several aspects. Testicular tissue cryopreservation, on the other hand, is still experimental for prepubertal boys. The primary aim of this review is to address the strategies available for possible fertility preservation in prepubertal girls and boys, such as ovarian cryopreservation/transplantation, in vitro follicle culture and meiotic maturation, artificial ovary, transplantation of cryopreserved spermatogonia, and cryopreservation/grafting of immature testicular tissue and testicular organoids.
Topics: Humans; Male; Female; Fertility Preservation; Quality of Life; Cryopreservation; Neoplasms; Testis
PubMed: 37770817
DOI: 10.1007/s10815-023-02945-2 -
MBio Jan 2024messenger RNA (mRNA) vaccines are a key technology in combating existing and emerging infectious diseases. However, the inherent instability of mRNA and the...
messenger RNA (mRNA) vaccines are a key technology in combating existing and emerging infectious diseases. However, the inherent instability of mRNA and the nonspecificity of lipid nanoparticle-encapsulated (LNP) delivery systems result in the need for cold storage and a relatively short-duration immune response to mRNA vaccines. Herein, we develop a novel vaccine in the form of circRNAs encapsulated in LNPs, and the circular structure of the circRNAs enhances their stability. Lyophilization is considered the most effective method for the long-term preservation of RNA vaccines. However, this process may result in irreversible damage to the nanoparticles, particularly the potential disruption of targeting modifications on LNPs. During the selection of lymph node-targeting ligands, we found that LNPs modified with mannose maintained their physical properties almost unchanged after lyophilization. Additionally, the targeting specificity and immunogenicity remained unaffected. In contrast, even with the addition of cryoprotectants such as sucrose, the physical properties of LNPs were impaired, leading to an obvious decrease in immunogenicity. This may be attributed to the protective role of mannose on the surface of LNPs during lyophilization. Freshly prepared and lyophilized mLNP-circRNA vaccines elicited comparable immune responses in both the rabies virus model and the SARS-CoV-2 model. Our data demonstrated that mLNP-circRNA vaccines elicit robust immune responses while improving stability after lyophilization, with no compromise in tissue targeting specificity. Therefore, mannose-modified LNP-circRNA vaccines represent a promising vaccine design strategy.
Topics: RNA, Circular; Mannose; Vaccines; Immunity; Freeze Drying; RNA, Messenger
PubMed: 38078742
DOI: 10.1128/mbio.01775-23