Showing papers on "Transplantation published in 2023"
TL;DR: In this article , the authors investigated the growth and hemodynamics of growth hormone receptor (GHR) knockout xenografts without the use of adjuncts to prevent intrinsic graft growth after transplantation.
40 citations
TL;DR: Wang et al. as discussed by the authors tracked the effective reproduction number (Rt) of the predominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant Omicron BF.
Abstract: We tracked the effective reproduction number (Rt) of the predominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant Omicron BF.7 in Beijing in November–December 2022 by fitting a transmission dynamic model parameterized with real-time mobility data to (i) the daily number of new symptomatic cases on 1–11 November (when China’s zero-COVID interventions were still strictly enforced) and (ii) the proportion of individuals who participated in online polls on 10–22 December and self-reported to have been test-positive since 1 November. After China’s announcement of 20 measures to transition from zero-COVID, we estimated that Rt increased to 3.44 (95% credible interval (CrI): 2.82–4.14) on 18 November and the infection incidence peaked on 11 December. We estimated that the cumulative infection attack rate (IAR; that is, proportion of the population infected since 1 November) in Beijing was 75.7% (95% CrI: 60.7–84.4) on 22 December 2022 and 92.3% (95% CrI: 91.4–93.1) on 31 January 2023. Surveillance programs should be rapidly set up to monitor the evolving epidemiology and evolution of SARS-CoV-2 across China. With the lifting of the zero-COVID policy and requirements governing reporting case numbers in China, it has become imperative to estimate the dynamics and cumulative infection rate of SARS-CoV-2 to help guide public health responses.
36 citations
TL;DR: In this article , the authors characterized a case of long-term HIV-1 remission of a 53-year-old male who was carefully monitored for more than 9 years after allogeneic CCR5 Δ32/Δ32 HSCT performed for acute myeloid leukemia.
Abstract: Despite scientific evidence originating from two patients published to date that CCR5Δ32/Δ32 hematopoietic stem cell transplantation (HSCT) can cure human immunodeficiency virus type 1 (HIV-1), the knowledge of immunological and virological correlates of cure is limited. Here we characterize a case of long-term HIV-1 remission of a 53-year-old male who was carefully monitored for more than 9 years after allogeneic CCR5Δ32/Δ32 HSCT performed for acute myeloid leukemia. Despite sporadic traces of HIV-1 DNA detected by droplet digital PCR and in situ hybridization assays in peripheral T cell subsets and tissue-derived samples, repeated ex vivo quantitative and in vivo outgrowth assays in humanized mice did not reveal replication-competent virus. Low levels of immune activation and waning HIV-1-specific humoral and cellular immune responses indicated a lack of ongoing antigen production. Four years after analytical treatment interruption, the absence of a viral rebound and the lack of immunological correlates of HIV-1 antigen persistence are strong evidence for HIV-1 cure after CCR5Δ32/Δ32 HSCT.
14 citations
TL;DR: In this article , a review of the major challenges faced by artificial bone transplantation are systemtically analyzed and current methods and strategies to address these issues are discussed: 1) the need for developing a type of bone scaffold material with both biological and mechanical properties.
Abstract: It is an urgent need that defect repair can develop from simple device fixation to living tissue reconstruction, from short life function replacement to permanent regeneration repair. At present, bone transplantation has become the second largest transplantation surgery after blood transfusion, and artificial bone transplantation generates great hope for the repair and treatment of bone defect. In order to repair bone defect, artificial bone must have good biological properties and sufficient mechanical properties, and it should also have the shape matching to bone defect site and the connected porous structure. For structures and properties requirements of artificial bone, in this review three major challenges faced by artificial bone transplantation are systemtically analyzed and current methods and strategies to address these issues are discussed: 1) the need for developing a type of bone scaffold material with both biological and mechanical properties, 2) the need for realizing the controllable fabrication of individual shape and multistage pore structure of bone scaffold, 3) the need for realizing the transformation from man‐made structure to biological structure. Besides, it summarizes the advantages and disadvantages of these methods and discusses the potential future directions of structural and functional adaptive artificial bone for bone defect regeneration.
14 citations
TL;DR: In this paper , DNA sequencing was performed on pretransplant blood from patients aged 18 years or older who had undergone their first allogeneic hematopoietic cell transplant during first remission for acute myeloid leukemia associated with variants in FLT3, NPM1, IDH1 or KIT at 1 of 111 treatment sites from 2013 through 2019.
Abstract: Importance
Preventing relapse for adults with acute myeloid leukemia (AML) in first remission is the most common indication for allogeneic hematopoietic cell transplant. The presence of AML measurable residual disease (MRD) has been associated with higher relapse rates, but testing is not standardized.
Objective
To determine whether DNA sequencing to identify residual variants in the blood of adults with AML in first remission before allogeneic hematopoietic cell transplant identifies patients at increased risk of relapse and poorer overall survival compared with those without these DNA variants.
Design, Setting, and Participants
In this retrospective observational study, DNA sequencing was performed on pretransplant blood from patients aged 18 years or older who had undergone their first allogeneic hematopoietic cell transplant during first remission for AML associated with variants in FLT3, NPM1, IDH1, IDH2, or KIT at 1 of 111 treatment sites from 2013 through 2019. Clinical data were collected, through May 2022, by the Center for International Blood and Marrow Transplant Research.
Exposure
Centralized DNA sequencing of banked pretransplant remission blood samples.
Main Outcomes and Measures
The primary outcomes were overall survival and relapse. Day of transplant was considered day 0. Hazard ratios were reported using Cox proportional hazards regression models.
Results
Of 1075 patients tested, 822 had FLT3 internal tandem duplication (FLT3-ITD) and/or NPM1 mutated AML (median age, 57.1 years, 54% female). Among 371 patients in the discovery cohort, the persistence of NPM1 and/or FLT3-ITD variants in the blood of 64 patients (17.3%) in remission before undergoing transplant was associated with worse outcomes after transplant (2013-2017). Similarly, of the 451 patients in the validation cohort who had undergone transplant in 2018-2019, 78 patients (17.3%) with residual NPM1 and/or FLT3-ITD variants had higher rates of relapse at 3 years (68% vs 21%; difference, 47% [95% CI, 26% to 69%]; HR, 4.32 [95% CI, 2.98 to 6.26]; P < .001) and decreased survival at 3 years (39% vs 63%; difference, -24% [2-sided 95% CI, -39% to -9%]; HR, 2.43 [95% CI, 1.71 to 3.45]; P < .001).
Conclusions and Relevance
Among patients with acute myeloid leukemia in first remission prior to allogeneic hematopoietic cell transplant, the persistence of FLT3 internal tandem duplication or NPM1 variants in the blood at an allele fraction of 0.01% or higher was associated with increased relapse and worse survival compared with those without these variants. Further study is needed to determine whether routine DNA-sequencing testing for residual variants can improve outcomes for patients with acute myeloid leukemia.
13 citations
TL;DR: In this article , a culture system that allows the long-term ex vivo expansion of human haematopoietic stem cells, achieved through the complete replacement of exogenous cytokines and albumin with chemical agonists and a caprolactam-based polymer.
Abstract: Haematopoietic stem cells (HSCs) are a rare cell type that reconstitute the entire blood and immune systems after transplantation and can be used as a curative cell therapy for a variety of haematological diseases1,2. However, the low number of HSCs in the body makes both biological analyses and clinical application difficult, and the limited extent to which human HSCs can be expanded ex vivo remains a substantial barrier to the wider and safer therapeutic use of HSC transplantation3. Although various reagents have been tested in attempts to stimulate the expansion of human HSCs, cytokines have long been thought to be essential for supporting HSCs ex vivo4. Here we report the establishment of a culture system that allows the long-term ex vivo expansion of human HSCs, achieved through the complete replacement of exogenous cytokines and albumin with chemical agonists and a caprolactam-based polymer. A phosphoinositide 3-kinase activator, in combination with a thrombopoietin-receptor agonist and the pyrimidoindole derivative UM171, were sufficient to stimulate the expansion of umbilical cord blood HSCs that are capable of serial engraftment in xenotransplantation assays. Ex vivo HSC expansion was further supported by split-clone transplantation assays and single-cell RNA-sequencing analysis. Our chemically defined expansion culture system will help to advance clinical HSC therapies. A culture system allows the long-term expansion of human haematopoietic stem cells (HSCs) in vivo without the use of recombinant cytokines or albumin, with potential applications for clinical therapies involving HSCs.
12 citations
TL;DR: In this article , a randomized controlled phase III trial was conducted to investigate the impact of hypothermic oxygenated perfusion (HOPE) on cumulative complications within a 12-month period after liver transplantation.
12 citations
TL;DR: In this article , the authors evaluated the role of ASCT in younger patients and maintenance rituximab (MR) after bendamustine plus RituxIMab (BR) for mantle cell lymphoma.
Abstract: Commonly used first-line (1L) treatments for mantle cell lymphoma include high-dose cytarabine-based induction followed by autologous stem-cell transplant (ASCT) for younger patients and several chemoimmunotherapy regimens for older patients. Continuous debates exist on the role of ASCT in younger patients and maintenance rituximab (MR) after bendamustine plus rituximab (BR).Retrospective data from 4,216 patients with mantle cell lymphoma in the Flatiron Health electronic record-derived deidentified database diagnosed between 2011 and 2021, mostly in US community oncology settings, were evaluated for treatment patterns and outcomes. The efficacy findings with ASCT and MR were validated in an independent cohort of 1,168 patients from 12 academic centers.Among 3,614 patients with documented 1L treatment, BR was the most used. Among 1,265 patients age < 65 years, 30.5% received cytarabine-based induction and 23.5% received ASCT. There was no significant association between ASCT and real-world time to next treatment (hazard ratio [HR], 0.84; 95% CI, 0.68 to 1.03; P = .10) or overall survival (HR, 0.86; 95% CI, 0.63 to 1.18; P = .4) among ASCT-eligible patients. Among MR-eligible patients, MR after BR versus BR alone was associated with a longer real-world time to next treatment (HR, 1.96; 95% CI, 1.61 to 2.38; P < .001) and overall survival (HR, 1.51; 95% CI, 1.19 to 1.92; P < .001). The efficacy findings were consistent in the validation cohort.In this large cohort of patients treated primarily in the US community setting, only one in four young patients received cytarabine or ASCT consolidation, suggesting the need to develop treatments that can be delivered effectively in routine clinical practice. Together with the validation cohort, data support future clinical trials exploring regimens without ASCT consolidation in young patients, whereas MR should be considered for patients after 1L BR and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.
12 citations
TL;DR: The results of the STEMS clinical trial as mentioned in this paper showed that the highest dosage of human fetal precursor cells (HfNPCs) significantly reduced brain atrophy and increased cerebrospinal fluid levels of anti-inflammatory and neuroprotective molecules.
Abstract: Abstract Innovative pro-regenerative treatment strategies for progressive multiple sclerosis (PMS), combining neuroprotection and immunomodulation, represent an unmet need. Neural precursor cells (NPCs) transplanted in animal models of multiple sclerosis have shown preclinical efficacy by promoting neuroprotection and remyelination by releasing molecules sustaining trophic support and neural plasticity. Here we present the results of STEMS, a prospective, therapeutic exploratory, non-randomized, open-label, single-dose-finding phase 1 clinical trial ( NCT03269071 , EudraCT 2016-002020-86), performed at San Raffaele Hospital in Milan, Italy, evaluating the feasibility, safety and tolerability of intrathecally transplanted human fetal NPCs ( hf NPCs) in 12 patients with PMS (with evidence of disease progression, Expanded Disability Status Scale ≥6.5, age 18–55 years, disease duration 2–20 years, without any alternative approved therapy). The safety primary outcome was reached, with no severe adverse reactions related to hf NPCs at 2-year follow-up, clearly demonstrating that hf NPC therapy in PMS is feasible, safe and tolerable. Exploratory secondary analyses showed a lower rate of brain atrophy in patients receiving the highest dosage of hf NPCs and increased cerebrospinal fluid levels of anti-inflammatory and neuroprotective molecules. Although preliminary, these results support the rationale and value of future clinical studies with the highest dose of hf NPCs in a larger cohort of patients.
9 citations
TL;DR: In this paper , the authors compared defibrotide prophylaxis plus best supportive care (BSC) versus best supportive Care alone for sinusoidal obstruction syndrome prevention after haematopoietic stem-cell transplantation (HSCT).
9 citations
TL;DR: The authors in this article performed a retrospective analysis of adults at the Cleveland Clinic with Stanford Integrated Psychosocial Assessment for Transplant scores before primary left ventricular assist device program implantation from April 1, 2013, to December 31, 2018.
TL;DR: Using longitudinal brain imaging and physiological phenotypes from the UK Biobank, this article established normative models of biological age for three brain and seven body systems, revealing a multiorgan aging network.
Abstract: Biological aging of human organ systems reflects the interplay of age, chronic disease, lifestyle and genetic risk. Using longitudinal brain imaging and physiological phenotypes from the UK Biobank, we establish normative models of biological age for three brain and seven body systems. Here we find that an organ's biological age selectively influences the aging of other organ systems, revealing a multiorgan aging network. We report organ age profiles for 16 chronic diseases, where advanced biological aging extends from the organ of primary disease to multiple systems. Advanced body age associates with several lifestyle and environmental factors, leukocyte telomere lengths and mortality risk, and predicts survival time (area under the curve of 0.77) and premature death (area under the curve of 0.86). Our work reveals the multisystem nature of human aging in health and chronic disease. It may enable early identification of individuals at increased risk of aging-related morbidity and inform new strategies to potentially limit organ-specific aging in such individuals.
TL;DR: In this article , the authors present a review of current knowledge on individual enhanced recovery elements on short-term outcomes, identify key components for comprehensive pathways, and create internationally accepted guidelines on enhanced recovery for livertransplant recipients.
TL;DR: In this article , the authors performed fecal microbiota transplantation (FMT) from young mice to aged mice and observed significant increment in lymphoid differentiation and decrease in myeloid differentiation in aged recipient mice.
TL;DR: The authors reported the first remission and possible HIV-1 cure in a mixed-race woman who received a CCR5Δ32/Δ 32 haplo-cord transplant (cord blood cells combined with haploidentical stem cells from an adult) to treat acute myeloid leukemia (AML).
TL;DR: In this paper , liver offers were counted from donation after circulatory death (DCD) donors (Maastricht type III) arising during the past decade in eight countries, including Belgium, France, Italy, Spain, Switzerland, the UK, and the US.
TL;DR: The authors of as discussed by the authors proposed a set of diagnostic and prognostic features for transplantation-associated thrombotic microangiopathy (TA-TMA) associated with significant morbidity and mortality.
TL;DR: In this paper , the authors describe and risk-stratify different profiles of patients listed for heart transplant supported by extracorporeal membrane oxygenation (ECMO), and assess 1-year survival in patients bridged to transplant with ECMO and patients who were previously supported on ECMO but had it removed before HT (ECMOREMOVED).
TL;DR: Fecal microbiota transplantation (FMT) is a treatment method traditionally used for Clostridium difficile infections, but it has recently been used in neurodegenerative disease research as a potential treatment method as mentioned in this paper .
Abstract: Neurodegenerative diseases are highly prevalent but poorly understood, and with few treatment options despite decades of intense research, attention has recently shifted toward other mediators of neurological disease that may present future targets for therapeutic research. One such mediator is the gut microbiome, which communicates with the brain through the gut–brain axis and has been implicated in various neurological disorders. Alterations in the gut microbiome have been associated with numerous neurological and other diseases, and restoration of the dysbiotic gut has been shown to improve disease conditions. One method of restoring a dysbiotic gut is via fecal microbiota transplantation (FMT), recolonizing the “diseased” gut with normal microbiome. Fecal microbiota transplantation is a treatment method traditionally used for Clostridium difficile infections, but it has recently been used in neurodegenerative disease research as a potential treatment method. This review aims to present a summary of neurodegenerative research that has used FMT, whether as a treatment or to investigate how the microbiome influences pathogenesis.
TL;DR: A guideline for the management of patients requiring acute mechanical circulatory support (MCS) was developed by the International Society of Heart and Lung Transplantation and the Heart Failure Society of America as mentioned in this paper .
Abstract: In spite of medical advances, cardiogenic and pulmonary shock are associated with high mortality and morbidity. The availability and use of acute or temporary mechanical support devices has grown over the years, with the goal of improving patient outcomes by temporarily providing support to allow time for organ recovery or for longer-term decisions including transition to durable therapies. A collaborative effort commissioned by the International Society of Heart and Lung Transplantation and the Heart Failure Society of America has developed this critically-needed guideline for the management of patients requiring acute mechanical circulatory support (MCS). The document covers definitions of cardiogenic and pulmonary shock, medical treatment and surgical interventions, management of patients supported with temporary devices, complications, special populations, and social and ethical dilemmas. The writing groups include multidisciplinary members from both societies with a focus on diversity in gender, geography, area of expertise and level of seniority. The target audience includes cardiologists, especially interventional and advanced heart failure, pulmonarycritical care specialists, intensivists, cardiothoracic surgeons, as well as referring providers.
TL;DR: In this paper , the authors make decisions to transplant organs from severe acute respiratory syndrome coronavirus 2 (SARS•CoV•2) nucleic acid test positive (NAT+) donors must balance risk of donor-derived transmission events (DDTE) with the scarcity of available organs.
Abstract: Decisions to transplant organs from severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) nucleic acid test‐positive (NAT+) donors must balance risk of donor‐derived transmission events (DDTE) with the scarcity of available organs.
TL;DR: In this article , the authors evaluated the effect of hypothermia as compared with machine perfusion on outcomes after kidney transplantation and concluded that the combination of both methods was superior to each individual therapy.
Abstract: Therapeutic hypothermia in brain-dead organ donors has been shown to reduce delayed graft function in kidney recipients after transplantation. Data are needed on the effect of hypothermia as compared with machine perfusion on outcomes after kidney transplantation.At six organ-procurement facilities in the United States, we randomly assigned brain-dead kidney donors to undergo therapeutic hypothermia (hypothermia group), ex situ kidney hypothermic machine perfusion (machine-perfusion group), or both (combination-therapy group). The primary outcome was delayed graft function in the kidney transplant recipients (defined as the initiation of dialysis during the first 7 days after transplantation). We also evaluated whether hypothermia alone was noninferior to machine perfusion alone and whether the combination of both methods was superior to each of the individual therapies. Secondary outcomes included graft survival at 1 year after transplantation.From 725 enrolled donors, 1349 kidneys were transplanted: 359 kidneys in the hypothermia group, 511 in the machine-perfusion group, and 479 in the combined-therapy group. Delayed graft function occurred in 109 patients (30%) in the hypothermia group, in 99 patients (19%) in the machine-perfusion group, and in 103 patients (22%) in the combination-therapy group. Adjusted risk ratios for delayed graft function were 1.72 (95% confidence interval [CI], 1.35 to 2.17) for hypothermia as compared with machine perfusion, 1.57 (95% CI, 1.26 to 1.96) for hypothermia as compared with combination therapy, and 1.09 (95% CI, 0.85 to 1.40) for combination therapy as compared with machine perfusion. At 1 year, the frequency of graft survival was similar in the three groups. A total of 10 adverse events were reported, including cardiovascular instability in 9 donors and organ loss in 1 donor owing to perfusion malfunction.Among brain-dead organ donors, therapeutic hypothermia was inferior to machine perfusion of the kidney in reducing delayed graft function after transplantation. The combination of hypothermia and machine perfusion did not provide additional protection. (Funded by Arnold Ventures; ClinicalTrials.gov number, NCT02525510.).
TL;DR: In this paper , the authors performed a narrative review of relevant academic and grey literature and revised their results after consultation with two national experts and synthesized according to a conceptual framework for organ donation and transplantation programs.
Abstract: Over the past two decades, Portugal has become one of the world leaders in organ donation and transplantation despite significant financial constraints. This study highlights how Portugal achieved success in organ donation and transplantation and discusses how this information might be used by other countries that are seeking to reform their national programs. To accomplish this goal, we performed a narrative review of relevant academic and grey literature and revised our results after consultation with two national experts. Our findings were then synthesized according to a conceptual framework for organ donation and transplantation programs. Our results revealed several key strategies used by the Portuguese organ donation and transplantation program, including collaboration with Spain and other European nations, a focus on tertiary prevention, and sustained financial commitment. This report also explores how cooperative efforts were facilitated by geographical, governmental, and cultural proximity to Spain, a world leader in organ donation and transplantation. In conclusion, our review of the Portuguese experience provides insight into the development of organ donation and transplantation systems. However, other countries seeking to reform their national transplant systems will need to adapt these policies and practices to align with their unique cultures and contexts. Graphical Abstract
TL;DR: In this paper , a 47-year old male with ischaemic cardiomyopathy was referred to us for durable left ventricular assist device placement, which was found to have prohibitively elevated pulmonary vascular resistance for heart transplantation.
Abstract: A 47‐year old male with ischaemic cardiomyopathy was referred to us for durable left ventricular assist device placement. He was found to have prohibitively elevated pulmonary vascular resistance for heart transplantation. He underwent HeartMate 3 left ventricular assist device implantation, with additional temporary right ventricular assist device (RVAD) placement. Following a 2‐week period of unweanable temporary right ventricular support, the patient was switched to durable biventricular support with two Heartmate 3 pumps. The patient was placed on a transplant waiting list but was not offered a heart for over 4 years. While on Heartmate 3 biventricular support (BiVAD), he returned to full activity and enjoyed an excellent quality of life. He underwent laparoscopic cholecystectomy 7 months after the BIVAD implant. After 52 months of uneventful BiVAD support, he presented with a combination of adverse events that occurred over a short period. These included subarachnoidal haemorrhage and a new motor deficit, followed by RVAD infection and RVAD low‐flow alarms. After over 4 years of unimpeded RVAD flows, new imaging revealed an outflow graft twist with subsequent flow reduction. The patient underwent heart transplantation after a total of 1655 days of Heartmate 3 BiVAD support and continues to do well on latest follow‐up.
TL;DR: In this article , a consensus report provides clinical practice recommendations in kidney, heart, lung, and liver transplantation based on expert assessment of quality and strength of evidence, including guidance regarding posttransplant DSA assessment and application to diagnostics, prognostics, and therapeutics.
TL;DR: The A Brain-Based Definition of Death and Criteria for its Determination After Arrest of Neurologic or Circulatory Function in Canada project was undertaken to a develop a unified brain-based definition of death, and to establish criteria for its determination after devastating brain injury and/or circulatory arrest as mentioned in this paper .
Abstract: Clarity regarding the biomedical definition of death and the criteria for its determination is critical to inform practices in clinical care, medical research, law, and organ donation. While best practices for death determination by neurologic criteria and circulatory criteria were previously outlined in Canadian medical guidelines, several issues have arisen to force their reappraisal. Ongoing scientific discovery, corresponding changes in medical practice, and legal and ethical challenges compel a comprehensive update. Accordingly, the A Brain-Based Definition of Death and Criteria for its Determination After Arrest of Neurologic or Circulatory Function in Canada project was undertaken to a develop a unified brain-based definition of death, and to establish criteria for its determination after devastating brain injury and/or circulatory arrest. Specifically, the project had three objectives: (1) to clarify that death is defined in terms of brain functions; (2) to clarify how a brain-based definition of death is articulated; and (3) to clarify the criteria for determining if the brain-based definition is met. The updated death determination guideline therefore defines death as the permanent cessation of brain function and describes corresponding circulatory and neurologic criteria to ascertain the permanent cessation of brain function. This article explores the challenges that prompted revisions to the biomedical definition of death and the criteria for its determination and outlines the rationales underpinning the project's three objectives. By clarifying that all death is defined in terms of brain function, the project seeks to align guidelines with contemporary medicolegal understandings of the biological basis of death.RéSUMé: Il est essentiel que la définition biomédicale du décès et les critères de sa détermination soient précis afin d’éclairer les pratiques en matière de soins cliniques, de recherche médicale, de droit et de don d’organes. Alors que les meilleures pratiques pour la détermination du décès par des critères neurologiques et circulatoires ont déjà été décrites dans les lignes directrices médicales canadiennes, plusieurs problèmes ont été soulevés, lesquels ont motivé leur réévaluation. Les découvertes scientifiques en cours, les changements correspondants dans la pratique médicale et les défis juridiques et éthiques imposent une mise à jour complète. Par conséquent, le projet d’Élaboration d’une définition uniformisée de la mort cérébrale et de critères fondés sur des données probantes pour sa détermination au Canada a été entrepris dans le but d’élaborer une définition uniformisée de la mort cérébrale et d’établir des critères pour sa détermination après une lésion cérébrale dévastatrice et/ou un arrêt circulatoire. Plus précisément, le projet avait trois objectifs : (1) clarifier que le décès est défini en termes de fonctions cérébrales; (2) clarifier la façon dont une définition cérébrale du décès est articulée; et (3) clarifier les critères permettant de déterminer si la définition de mort cérébrale est respectée. Les lignes directrices mises à jour sur la détermination du décès définissent donc le décès comme l’arrêt permanent de la fonction cérébrale et décrivent les critères circulatoires et neurologiques correspondants pour établir l’arrêt permanent de la fonction cérébrale. Cet article explore les défis qui ont motivé la révision de la définition biomédicale du décès et des critères de sa détermination et décrit les raisons d’être qui sous-tendent les trois objectifs du projet. En précisant que tout décès est défini en termes de fonction cérébrale, le projet cherche à aligner les lignes directrices sur les compréhensions médicolégales contemporaines des fondements biologiques de la mort.
TL;DR: The authors in this paper presented a narrative literature review of the Spanish organ donation and transplantation program supplemented by expert feedback and presented according to a conceptual framework of best practices in the field, including three-tiered governing structure, close and collaborative relationships with the media, dedicated professional roles, a comprehensive reimbursement strategy, and intensive tailored training programs for all personnel.
Abstract: The organ donation and transplantation program in Spain has long been considered the gold standard worldwide. An in-depth understanding of the Spanish program may promote the development and reform of transplant programs in other countries. Here, we present a narrative literature review of the Spanish organ donation and transplantation program supplemented by expert feedback and presented according to a conceptual framework of best practices in the field. Core features of the Spanish program include its three-tiered governing structure, close and collaborative relationships with the media, dedicated professional roles, a comprehensive reimbursement strategy, and intensive tailored training programs for all personnel. Several more sophisticated measures have also been implemented, including those focused on advanced donation after circulatory death (DCD) and expanded criteria for organ donation. The overall program is driven by a culture of research, innovation, and continuous commitment and complemented by successful strategies in prevention of end-stage liver and renal disease. Countries seeking ways to reform their current transplant systems might adopt core features and may ultimately aspire to include the aforementioned sophisticated measures. Countries intent on reforming their transplant system should also introduce programs that support living donation, an area of the Spanish program with potential for further improvement. Graphical Abstract
TL;DR: Gupta et al. as discussed by the authors reported the emergence of resistant SARS-CoV-2 variants in immunocompromised patients after monoclonal antibody (mAb) therapy, which is a weakness of such therapy when treating a mutagenic and variable virus.
Abstract: COVID-19 in immunocompromised hosts has emerged as a difficult therapeutic management problem. Immunocompromised hosts mount weak responses to SARS-CoV-2 and manifest infection outcomes ranging from severe disease to persistent infection. Weakened immune systems mean greater viral loads and increased opportunities for viral evolution. Gupta, Konnova, et al. report the emergence of resistant SARS-CoV-2 variants in immunocompromised patients after monoclonal antibody (mAb) therapy. mAbs target only a single determinant in the viral Spike protein, which is a weakness of such therapy when treating a mutagenic and variable virus. Hence, the emergence of mAb resistance could have been anticipated, but its documentation is important because it has major public health implications, since such resistant variants have the potential to spread and escape vaccine immunity. For immunocompromised patients, these findings suggest the need for combination therapy with antiviral drugs and the use of polyclonal antibody preparations such as convalescent plasma.
TL;DR: T-cell receptor excision circle (TREC)-based newborn screening (NBS) for severe combined immunodeficiencies (SCID) was introduced in Germany in August 2019 as mentioned in this paper .
Abstract: T-cell receptor excision circle (TREC)-based newborn screening (NBS) for severe combined immunodeficiencies (SCID) was introduced in Germany in August 2019.Children with abnormal TREC-NBS were referred to a newly established network of Combined Immunodeficiency (CID) Clinics and Centers. The Working Group for Pediatric Immunology (API) and German Society for Newborn Screening (DGNS) performed 6-monthly surveys to assess the TREC-NBS process after 2.5 years.Among 1.9 million screened newborns, 88 patients with congenital T-cell lymphocytopenia were identified (25 SCID, 17 leaky SCID/Omenn syndrome (OS)/idiopathic T-cell lymphocytopenia, and 46 syndromic disorders). A genetic diagnosis was established in 88%. Twenty-six patients underwent hematopoietic stem cell transplantation (HSCT), 23/26 within 4 months of life. Of these, 25/26 (96%) were alive at last follow-up. Two patients presented with in utero onset OS and died after birth. Five patients with syndromic disorders underwent thymus transplantation. Eight syndromic patients deceased, all from non-immunological complications. TREC-NBS missed one patient, who later presented clinically, and one tracking failure occurred after an inconclusive screening result.The German TREC-NBS represents the largest European SCID screening at this point. The incidence of SCID/leaky SCID/OS in Germany is approximately 1:54,000, very similar to previous observations from North American and European regions and countries where TREC-NBS was implemented. The newly founded API-CID network facilitates tracking and treatment of identified patients. Short-term HSCT outcome was excellent, but NBS and transplant registries will remain essential to evaluate the long-term outcome and to compare results across the rising numbers of TREC-NBS programs across Europe.