Indirect Basophil Activation Test for Peanut Allergy Diagnosis Using Human Donor Basophils.

The basophil activation test (BAT) is a promising test for the replacement of the expensive, time-consuming, and patient-unfriendly oral food challenge (OFC). However, the BAT requires a fresh blood sample which has to be analyzed within 1 day, which can be a logistical constraint. The indirect or passive basophil activation test (iBAT) with human donor basophils and patient serum that can be stored for a long time (1) enables laboratories to perform the assay at any time, (2) gives the possibility to analyze different allergens in the course of time without the need of a new blood sample, and (3) does not suffer from inconclusive results due to nonresponder basophils. The advantage of this iBAT with human donor basophils over the use of basophil or mast cell lines is that this iBAT can be executed without the need of laboratory facilities for cell culture.

[Fundamentals of organ and tissue procurement]. / Les fondamentaux concernant le prélèvement d'organes et de tissus.

Transplantation is the treatment of choice for the terminal evolution of many organ failures. This recent solution has been deployed in France, essentially from deceased donors, in a state of encephalic death or after circulatory arrest. The ethical issues raised by these practices are strictly regulated. The Agence de la biomédecine, in conjunction with healthcare professionals and supervisory authorities, is the public operator in charge of organizing and developing the procurement activities. The volume of activity, severely disrupted by the Covid-19 pandemic, is now back on the rise. The 2022-2026 transplant plan sets ambitious but realistic targets to meet the needs of waiting patients.

[Organ donation is not a gift]. / Le don d'organes n'est pas un don.

If the obligation to donate as defined by French law ("we are all donors") remains in the wake of sociologist Marcel Mauss's Essai sur le don (Essay on donation), there the similarity ends. How do you make a counter-donation to a deceased person? In the case of inter vivos organ donation, the act is more akin to mutualization than donation.

Pneumatosis cystoides intestinalis mimicking free intraabdominal air following chemotherapy for relapsed acute myeloblastic leukemia in a transplanted neutropenic child: a case report.

BACKGROUND: Pneumatosis cystoides intestinalis (PI) is a rare but important condition in which widespread air sacs are found in the submucosa, and subserosa of the bowel wall. Although it has several etiologies, children receiving chemotherapy are at risk for PI. Preferred imaging tools for the diagnosis are abdominal direct radiography and computed tomography. In patients with PI, rupture of intramural air sacs is the source of benign pneumoperitoneum, causing free air without true intestinal perforation. Intestinal perforation or obstruction are indications for surgical intervention. CASE: Here, we present a 4-year-old patient diagnosed with acute myeloblastic leukemia (AML), who underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a matched sibling donor (MSD) and developed PI after HSCT. The patient was consulted to the pediatric surgery department, and her oral feeding was stopped. Broad spectrum antibiotics (teicoplanin, metronidazol and vancomycin) were initiated. Her fever increased during the 24-hour monitoring, there was no stool passage, CRP ( > 25 mg/dL, normal value < 1 mg/dL) and abdominal distension increased and there was prolonged neutropenia and radiologic investigations could not rule out intestinal perforation, so the patient underwent exploratory laparotomy. No intestinal perforation was found. There was no sign in the intestinal wall and numerous gas-filled cysts of various sizes. CONCLUSIONS: PI is an uncommon complication, and direct radiography/computed tomography scans are very helpful in making the diagnosis in suspicious cases. PI, should be kept in mind, especially in transplanted or relapsed leukemia patients receiving intensive chemotherapy.

Intestinal Donation and Utilization: Single-Center Analysis Within Eurotransplant.

Intestinal donor criteria are classically kept strict, thereby limiting donor supply. Indications for intestinal transplantation (ITx) are rare, but improved outcome and new emerging indications lead to increased demand and relaxing donor criteria should be considered. We sought to compare the donor criteria of intestines transplanted at our center with predefined (per protocol) criteria, and to determine how relaxing donor criteria could impact the potential donor pool. Donor criteria used in 22 consecutive ITx at our center between 2000 and 2020 were compared with predefined criteria. Next, multiorgan donors effectively offered by our Donor Network to Eurotransplant between 2014 and 2020 were retrospectively screened, according to predefined and effectively used intestinal donation criteria. Finally, utilization rate of offered intestines was calculated. In our ITx series, the effectively used donor criteria were less strict than those initially predefined. With these relaxed criteria, a favorable 5-year graft/patient survival of 75% and 95%, respectively was reached. Applying these relaxed criteria would lead to a 127% increase in intestinal offers. Paradoxically, 70% of offered intestines were not used. In conclusion, a significant increase in intestinal donation could be obtained by relaxing donor criteria, while still achieving excellent outcome. Offered intestines are underutilized.

Management of the sensitized heart transplant candidate.

PURPOSE OF REVIEW: For sensitized heart transplant candidates who have antibodies to human leukocyte antigens (HLA), finding a suitable donor can be challenging and can lead to adverse waitlist outcomes. In recent years, the number of sensitized patients awaiting heart transplantation has increased likely due to the use of durable and mechanical circulatory support as well as increasing number of candidates with underlying congenital heart disease. RECENT FINDINGS: Advances in the assessment of HLA antibodies allow for identification of heart transplant candidates who may benefit from desensitization strategies to widen the donor pool and mitigate the risk of adverse posttransplant outcomes. SUMMARY: Antibody sensitization is a barrier to successful heart transplantation and strategies to identify sensitized patients, stratify their risk, and mitigate this risk through desensitization is crucial to optimize the quality of life and survival of HT recipients.

A Neonatal Heterotopic Rat Heart Transplantation Model for the Study of Endothelial-to-Mesenchymal Transition.

Endocardial fibroelastosis (EFE), defined by subendocardial tissue accumulation, has major impacts on the development of the left ventricle (LV) and precludes patients with congenital critical aortic stenosis and hypoplastic left heart syndrome (HLHS) from curative anatomical biventricular surgical repair. Surgical resection is currently the only available therapeutic option, but EFE often recurs, sometimes with an even more infiltrative growth pattern into the adjacent myocardium. To better understand the underlying mechanisms of EFE and to explore therapeutic strategies, an animal model suitable for preclinical testing was developed. The animal model takes into consideration that EFE is a disease of the immature heart and is associated with flow disturbances, as supported by clinical observations. Thus, the heterotopic heart transplantation of neonatal rat donor hearts is the basis for this model. A neonatal rat heart is transplanted into an adolescent rat's abdomen and connected to the recipient's infrarenal aorta and inferior vena cava. While perfusion of the coronary arteries preserves the viability of the donor heart, flow stagnation within the LV induces EFE growth in the very immature heart. The underlying mechanism of EFE formation is the transition of endocardial endothelial cells to mesenchymal cells (EndMT), which is a well-described mechanism of early embryonic development of the valves and septa but also the leading cause of fibrosis in heart failure. EFE formation can be macroscopically observed within days after transplantation. Transabdominal echocardiography is used to monitor the graft viability, contractility, and the patency of the anastomoses. Following euthanasia, the EFE tissue is harvested, and it shows the same histopathological characteristics as human EFE tissue from HLHS patients. This in vivo model allows for studying the mechanisms of EFE development in the heart and testing treatment options to prevent this pathological tissue formation and provides the opportunity for a more generalized examination of EndMT-induced fibrosis.

Synchronous Donor Heart and Lung Procurement Does Not Impair Outcomes After Heart Transplant.

OBJECTIVES: Donor hearts frequently originate from donors whose lungs are also recovered for transplant. Synchronous heart and lung procurement is more complex than procurement ofthe heart alone, and the effects on outcomes are debated. This study examines the effect of synchronous procurement on outcomes in heart transplant recipients. MATERIALS AND METHODS: This single-center study included patients who received a heart transplant from September 2010 to June 2022. Main outcomes were overall mortality and mortality at 30 days, 3 months, 1 year, and 3 years and morbidity within the first year. We analyzed overall mortality using KaplanMeier survival analysis. Logistic regression was used for the remaining outcomes, adjusting for covariates. P < .05 was considered significant. RESULTS: Our study included 253 heart transplant recipients (72.3% male, mean age 55.0 years), of which 184 patients (72.7%) received hearts from donors of heart and lung, and 69 (27.3%) received hearts from donors of only hearts. Heart-and-lung donors were younger than heart-only donors (43.2 vs 47.2 years; P = .017). Transplant recipient baseline characteristics were not different between the 2 groups. Receipt of hearts from heart-and-lung donors was not associated with higher overall mortality (P = .33) or mortality at 3 months (P = .199), 1 year (P = .348), or 3 years (P = .375), and even showed better 30-day survival than receipt of hearts from heart-only donors (p=0.035). Recipients of hearts from heart-and-lung donors did not have higher rates of postoperative mechanical circulatory support, resternotomy, or pacemaker implantation within the first year. CONCLUSIONS: Our study confirms that synchronous heart and lung procurement for transplant is not associated with worse outcomes in heart transplant recipients and that hearts originating from heart-andlung donors may even be associated with improved outcomes.

Immunoadsorption-Based HLA Desensitization in Patients Awaiting Deceased Donor Kidney Transplantation: An Interventional, Non-Randomised, Single Cohort Study.

Whether immunoadsorption (IADS) as part of desensitization protocols could facilitate deceased donor kidney transplantation (KT) in highly sensitized (HS) patients remains to be proven. We retrospectively analyzed our IADS based desensitization protocol for deceased donor KTs between 2013 and 2018. Fifteen HS patients (age 52 years [40-56]) were included. Waiting time before IADS was 6 years [5-10] and the interval between IADS initiation and KT was 5 months [1-12] for the 14 transplanted patients. Nine patients had prior KT. Calculated panel reactive antibody decreased significantly during the protocol (99.3% [92.5-99.9] vs. 79.4% [56.7-81.9]; p = 0.004). Death-censored graft survival was 85.7% at 1 and 2 years post-transplantation. One-year median plasma creatinine level was 135 µmol/L [111-202]. Six developed active antibody mediated rejection (ABMR) at 1 year, with a median delay of 13 days [11-26]. Eight patients developed severe infections, including two fatal outcomes. Finally, compared to 93% of patients who received desensitization receiving a KT, only 43% of a control with similar characteristics underwent transplantation. However, no difference was found in overall probability of being alive with a functioning graft at the end of follow-up. The results indicate that our IADS-based desensitization strategy was not effective due to a high rate of ABMR and severe infectious complications which pose a challenge to its universalization.

Robotic Bladder Autotransplantation: Preclinical Studies in Preparation for First-in-human Bladder Transplant.

PURPOSE: Human urinary bladder transplantation has never been performed. From a technical standpoint, challenges include the complex deep pelvic vascular anatomy, limited intraoperative visualization, and high procedural complexity. In preparation for a first-in-human clinical trial, we report preclinical studies to develop the technique of robotic retrieval and autotransplantation of vascularized composite bladder allograft. MATERIALS AND METHODS: Institutional Animal Care and Use Committee, Institutional Review Board, and UNOS (United Network for Organ Sharing) approvals were obtained, and IDEAL (Idea, Development, Exploration, Assessment, Long-term Study) Reporting Guidelines were followed. Robotic vascularized composite bladder allograft recovery, back-table graft preparation, and robotic autotransplantation were performed in 3 vascularized model settings: living porcine (n=3), pulsatile human cadavers (n=2), and heart-beating brain-dead deceased research human donors (n=5). Our primary objective was to develop a reproducible technique for robotic vascularized composite bladder allograft transplantation. Technical success was defined by adequate, sustained vascularized composite bladder allograft reperfusion. Secondary objectives were intraoperative parameters, including operative time, graft ischemia time, and blood loss. RESULTS: Successful robotic vascularized composite bladder allograft autotransplantation was achieved in 2 porcine, 1 cadaver, and 3 brain-dead research donors. In the heart-beating research donors, console time decreased with successive surgeries, and visual inspection revealed healthy revascularized autografts with prompt, global indocyanine green immunofluorescence uptake. In 1 heart-beating donor who was hemodynamically maintained for 12 hours postoperatively, reinspection confirmed excellent maintained global vascularized composite bladder allograft vascularity and bladder mucosal integrity. CONCLUSIONS: To our knowledge, the first preclinical experience of bladder autotransplantation in vascularized models is reported, including robotic vascularized composite bladder allograft recovery, back-table reconstruction, and autotransplantation. This experience represents the essential preclinical work required to build toward the first-in-human trial of bladder transplantation, performed under a UNOS-approved genitourinary vascularized composite bladder allograft program (NCT No. 05462561).

Chapitre 10. La part sociale des transplantations d'organes.

What do we share when we donate or receive an organ? What meaning does donation have in the mourning process of a loved one or in the therapeutic process of a transplant patient? These questions rarely reach the public arena, but they do animate the people who concretely participate in the circulation of organs, whether it is because they accept the removal of an organ, receive one or are in charge of organizing it. With this contribution, I wish to shed light on the answers to these questions, as they emerge in practice, and thereby expose the social component of these surgical operations. I first examine the trend towards the promotion of organ donation and transplantation since the 1970s; then I look at the limits for the patients of an approach to transplantation based solely on a biomedical prism; and finally I examine the horizon of possibilities in terms of recognition of the relationships that organ transplant can create between donors and receivers.

Chapitre 15. L'accès aux origines personnelles.

Law n° 2021-1017 of August 2nd. 2021 allows children born of assisted reproduction with a third party donor to have access, as of their majority, to non-identifying data and the identity of this third party. Without calling into question the principle of anonymity, it enshrines the right of access to origins. The reasons for this development are to be found in the evolution of European law, rather than in a logical evolution of French bioethics law. However, such an enshrinement is not without difficulties, both in terms of the concrete and technical implementation of this access to origins and in terms of the practical consequences in the realisation of access to this right for the children benefiting from this system.

Chapitre 17. Du père caché au père révélé, l'émergence d'un lien sui generis.

The bioethics bill reflects a paradigm shift in filiation. Indeed, the bill provides for the lifting of donor anonymity at the age of majority of the child born of the donation. However, the legislator does not provide for a specific legal regime qualifying the link between the donor and the child born of the donation. It thus proceeds to a negative qualification of a situation that nevertheless entails important legal consequences. One then wonders about the nature of this relationship and about the potential consequences induced by the lifting of anonymity, consequences that are both legal and social. This article will then make it possible to dissociate the notion of filiation and the progressive emergence of the right of access to one’s origins.

Theoretical Study of Structure and Photophysics of Homologous Series of Bis(arylydene)cycloalkanones.

Photophysical properties of a series of bis(arylydene)cycloalkanone dyes with various donor substituents are studied using quantum chemistry. Their capacity for luminescence and nonradiative relaxation through trans-cis isomerization is related to their structure, in particular, to the donor capacity of the substituents and the degree of conjugation due to the central cycloalkanone moiety. It is shown that cyclohexanone central moiety introduces distortions and disrupts the conjugation, thus leading to a nonmonotonic change in their properties. The increasing donor capacity of the substituents causes increase in the HOMO energy (rise in the oxidation potential) and decrease in the HOMO-LUMO gap, which results in the red shift of the absorption spectra. The ability of the excited dye to relax through fluorescence or through trans-cis isomerization is governed by the height of the barrier between the Franck-Condon and S1-S0 conical intersection regions on the potential energy surface of the lowest π-π* excited state. This barrier also correlates with the donor capacity of the substituents and the degree of conjugation between the central and donor moieties. The calculated fluorescence and trans-cis isomerization rates are in good agreement with the observed fluorescence quantum yields.

Sensitive Detection of Various Forms of Hydrogen Sulfide via Highly Selective Naphthalimide-Based Fluorescent Probe.

Hydrogen sulfide (H2S) is an important gasotransmitter, but only a few methods are available for real-time detection. Fluorescent probes are attractive tools for biological applications because of their high sensitivity, convenience, rapid implementation, noninvasive monitoring capability, and simplicity in fluorescent imaging of living cells and tissues. Herein, we report on a pro-fluorescent probe, NAP-Py-N3 based on naphthalimide derivative, which was found to show high selectivity toward H2S over various other analytes, including biothiols, making it feasible to detect H2S. After reaction with H2S, this probe showed rapid and significant turn-on green fluorescent enhancement at 553 nm (about 54-fold, k2 = 9.62 M-1s-1), high sensitivity (LOD: 15.5 nM), significant Stokes shift (118 nm), and it was found that the fluorescence quantum yield of fluorescence product can reach 0.36. Moreover, the probe has also been successfully applied to detect the gaseous H2S and to confirm the presence of H2S released from modern organic donors, which in recent years have been commonly used to investigate the role of H2S in biological systems. All the results indicate that this probe is excellent and highly valuable.

[Acute Aortic Dissection Complicated by IgA Deficiency].

Immunoglobulin A (IgA) deficiency is the most common type of primary immunodeficiency. When a patient receives a blood product transfusion, anti-IgA antibodies are formed. Second transfusion may sometimes cause an anaphylactic reaction, thus caution is necessary. Reported here is a case of Stanford type A acute aortic dissection performed in the patient with IgA deficiency with a history of blood transfusion. Red blood cells and platelet were washed and prepared, and flesh frozen plasma from IgA deficient donors was obtained. Thereafter, the surgery was safely performed.

Linking donor-specific antibody generation with natural killer cells in antibody-mediated kidney graft rejection.

Natural killer (NK) cell infiltration of kidney allografts is a distinguishing feature of antibody-mediated rejection. Bailly et al. identify a distinct population of cytotoxic CD160+ interleukin-21 receptor+ CD56dimCD16bright NK cells that are uniquely found in the peripheral blood of donor-specific antibody-positive kidney transplant recipients and are present in kidney allografts with active antibody-mediated rejection. This population is implicated in a T follicular helper/interleukin-21/NK cell axis that links donor-specific antibody generation with graft-infiltrating NK cells in antibody-mediated rejection.

Importance of human milk for infants in the clinical setting: Updates and mechanistic links.

INTRODUCTION: Human milk (HM) is the optimal source of nutrition for infants and has been implicated in multiple aspects of infant health. Although much of the existing literature has focused on the individual components that drive its nutrition content, examining HM as a biological system is needed for meaningful advancement of the field. Investigation of the nonnutritive bioactive components of HM and the maternal, infant, and environmental factors which affect these bioactives is important to better understand the importance of HM provision to infants. This information may inform care of clinical populations or infants who are critically ill, hospitalized, or who have chronic diseases and may benefit most from receiving HM. METHODS: In this narrative review, we reviewed literature examining maternal and infant influences on HM composition with a focus on studies published in the last 10 years that were applicable to clinical populations. RESULTS: We found multiple studies examining HM components implicated in infant immune and gut health and neurodevelopment. Additional work is needed to understand how donor milk and formula may be used in situations of inadequate maternal HM. Furthermore, a better understanding of how maternal factors such as maternal genetics and metabolic health influence milk composition is needed. CONCLUSION: In this review, we affirm the importance of HM for all infants, especially clinical populations. An understanding of how HM composition is modulated by maternal and environmental factors is important to progress the field forward with respect to mechanistic links between HM biology and infant health outcomes.

Donor activity is associated with US legislators' attention to political issues.

Campaign contributions are a staple of congressional life. Yet, the search for tangible effects of congressional donations often focuses on the association between contributions and votes on congressional bills. We present an alternative approach by considering the relationship between money and legislators' speech. Floor speeches are an important component of congressional behavior, and reflect a legislator's policy priorities and positions in a way that voting cannot. Our research provides the first comprehensive analysis of the association between a legislator's campaign donors and the policy issues they prioritize with congressional speech. Ultimately, we find a robust relationship between donors and speech, indicating a more pervasive role of money in politics than previously assumed. We use a machine learning framework on a new dataset that brings together legislator metadata for all representatives in the US House between 1995 and 2018, including committee assignments, legislative speech, donation records, and information about Political Action Committees. We compare information about donations against other potential explanatory variables, such as party affiliation, home state, and committee assignments, and find that donors consistently have the strongest association with legislators' issue-attention. We further contribute a procedure for identifying speech and donation events that occur in close proximity to one another and share meaningful connections, identifying the proverbial needles in the haystack of speech and donation activity in Congress which may be cases of interest for investigative journalism. Taken together, our framework, data, and findings can help increase the transparency of the role of money in politics.

Healthcare System Impact on Deceased Organ Donation and Transplantation: A Comparison Between the Top 10 Organ Donor Countries With 4 Countries in Southeast Asia.

The need for organ donation is constantly increasing. Some countries have made improvements, while others, such as countries in Southeast Asia (SEA), have some of the lowest rates of deceased donors (pmp). This review aims to compare 14 countries with regards to many variables related to healthcare systems. Countries leading in deceased organ donation spend more on health and education, which is associated with increased potential for deceased organ donation. Out-of-pocket expenditure, is also associated with a decrease in deceased organ donation. Countries in SEA are lacking in healthcare resources such as workforce and materials, which are both necessary for a successful transplant program. Most countries in SEA have an excellent foundation for successful organ donation systems, including proper legislation, government support, and brain death laws along with an overall acceptance of brain death diagnosis. Priorities should include improving coordination, donor identification, and healthcare worker education. Countries in SEA have a lot of potential to increase deceased organ donation, especially by investing in healthcare and education. There is no one size fits all for organ donation programs and countries in SEA should focus on their strengths and take cultural differences into consideration when planning interventions.