Pig kidney transplantation: an up-to-date guideline

Background: Swine and human beings have many aspects in common that make swine a well-characterized large animal model for kidney transplantation (KTx). However, pigs have some peculiar anatomical characteristics that standardized techniques must adapt to. The aim of this study was to prepare an up-to-date guideline for porcine KTx. Methods: To achieve this goal, we performed a Medline search using the terminology ”kidney’ or ”renal’ and ”transplantation’ and ”pig’ or ”swine’ or ”porcine’. We found over 1,300 published articles since 1963. Only 13 studies focused on the surgical aspect. Furthermore, we reviewed related books and articles about swine anatomical characteristics and surgery. Finally, our experimental experiences of KTx during the last few decades were added to this collection. Results: Proper hosting, fasting, anesthesia, medical therapy and monitoring can prevent postoperative complications. Explantation with a Carrel patch of the aorta facilitates the implantation and prevents future stenosis. Native nephrectomy makes the follow-up of the implanted organ more precise. KTx in the infrarenal fossa via end-to-side anastomosis to the aorta and inferior vena cava followed by ureteroureterostomy are the recommended options for KTx in pigs compared to other possible methods. Conclusion: Pigs, with respect to their characterizations, constitute one of the best large animal models for KTx. Preoperative preparations are as important as the intra- and postoperative management. Using the most adaptable methods of surgery with respect to the specific anatomical characteristics of pigs can prevent undermining the studies and avoid preventable complications and pitfalls. Copyright (c) 2012 S. Karger AG, Base

Characterization of Rate Dependency and Inhomogeneity of Aortic Tissue

Traumatic aortic rupture (TAR) is one of the leading causes of morbidity and mortality in motor-vehicle accidents with the majority of injuries occurring in the peri-isthmus region. To date, the mechanisms of aorta injury are poorly understood as this injury cannot be replicated reliably in cadaver crash tests. Due to inconclusiveness of the experimental tests, finite element (FE) modeling is often used to gain a better insight into the mechanisms of TAR. However, the FE models are also hindered by many unknowns particularly the soft tissues biomechanical responses. A crucial step to improve the FE models of blunt chest trauma is to advance our understanding of the local mechanical properties of aortic tissue subject to high loading rates associated with TAR. The objective of this dissertation was to investigate the effects of tissue rate dependency and inhomogeneity in the modeling of loading conditions that lead to TAR. The material properties of human aorta in large deformations and high loading rates were characterized based on oscillatory biaxial tests. It was shown that a quasilinear viscoelastic (QLV) model with the instantaneous elastic response of the second order and the reduced relaxation function with one exponentially decaying term could describe the experimental results between 20 Hz and 130 Hz. The obtained decay rates (in the range of 70 to 550 s-1) were 10 to 100 folds higher than previously reported values and showed significant rate dependence within 10 ms after the loading. It was shown that the rate dependent properties, similar to the elastic properties, were anisotropic with generally higher decay rate and stiffness observed in the circumferential direction compared to the longitudinal direction. The inhomogeneity of porcine descending thoracic aorta was characterized in three dimensions using a nano-indentation technique and QLV modeling approach. The tests were conducted in the axial, circumferential, and radial orientations with about 100 micrometer spatial resolution. Aortic tissue was divided into 10 regions across the thickness, 4 quadrants in the circumferential direction, and 3 sections in the longitudinal direction. While across the thickness, the results in different orientations were significantly different, four distinct layers were identified that were matched with the anatomical features. In the axial direction, the medial quadrant, and in all directions, the proximal DTA had the lowest stiffness. The results predict that under equal stresses, the inner layers of the medial quadrant in upper DTA would undergo more strains and will be therefore more prone to failure. This prediction is in agreement with clinical observations. The inhomogeneity and rate dependency of aorta were implemented in the Global Human Body Models Consortium full-body FE model. It was demonstrated that in a simulation of blunt chest impact, both features significantly affected the tissue strain levels particularly in the isthmus, arch, and ascending aorta. Accurate quantifications of these features are essential to assess the risk of aortic injury based on FE models.Mechanical Engineerin

Deconstructing and Approaching Heterogeneities in the Biomedical Field via Computational Modeling

Natural variation between human characteristics as well as differences across collected datasets in disparate medical or research centers on various levels (e.g., semantical and technical) lead to high heterogeneity in terms of patients and data in the biomedical field. These heterogeneities not only impede understanding of disease pathology and clinical diagnosis but also their implications in the treatment of disease are substantial. Moreover, these heterogeneities limit the impact of computational solutions on clinical practice in spite of their high potential in bringing significant advances in the biomedical domain. In this thesis, we address the aforementioned issues in the context of complex diseases, namely Alzheimer’s disease (AD) and multiple types of cancers. First, in an in-depth study, we shed light on hurdles derived from heterogeneities and out-line how they can restrict the impact of computational models in clinical practice with special focus in AD. Then, to demonstrate the findings of the preceding work, we present a comparative study on characterizing the order of pathological markers by applying a computational model, more specifically a data-driven one, to multiple independent datasets collected in different research centers. In this work, we investigate how heterogeneity across datasets can result in disparities among the ordering of changes in AD biomarkers and influence the models’ impact on clinical practices. Further, to provide a more meaningful biological context into AD pathology, we use a pure knowledge-driven approach to showcase different mechanisms of disease development and progression that genetic variants may cause. Finally, we conclude this thesis by proposing a novel methodology to address heterogeneity among cancer patients in the context of disease treatment. In this publication, with the help of highly predictive machine learning models and an innovative scoring algorithm, we evaluate whether a given sample that was formerly classified as diseased could be predicted as normal after treatment with a given drug taking into account the corresponding molecular signatures of that particular sample. In summary, this thesis presents the challenges and their implications brought on by heterogeneities in the biomedical domain in order to understand disease pathology and possible treatments, and attempt to uncover avenues to tackle the hindrances. Such advances have numerous applications in the biomedical field, ranging from patient stratification to drug discovery and achieving the ideal of precision medicine

Is clinical practice concordant with the changes in guidelines for antiretroviral therapy initiation during primary and chronic HIV-1 infection? The ANRS PRIMO and COPANA cohorts.

International audienceOBJECTIVE: Guidelines for initiating HIV treatment are regularly revised. We explored how physicians in France have applied these evolving guidelines for ART initiation over the last decade in two different situations: chronic (CHI) and primary HIV-1 infection (PHI), since specific recommendations for PHI are also provided in France. METHODS: Data came from the ANRS PRIMO (1267 patients enrolled during PHI in 1996-2010) and COPANA (800 subjects enrolled at HIV diagnosis in 2004-2008) cohorts. We defined as guidelines-inconsistent during PHI and CHI, patients meeting criteria for ART initiation and not treated in the following month and during the next 6 months, respectively. RESULTS: ART initiation during PHI dramatically decreased from 91% of patients in 1996-99 to 22% in 2007 and increased to 60% in 2010, following changes in recommendations. In 2007, however, after the CD4 count threshold was raised to 350 cells/mm(3) in 2006, only 55% of the patients with CD4≤350 were treated and 66% in 2008. During CHI, ART was more frequently initiated in patients who met the criteria at entry (96%) than during follow-up: 83% when recommendation to treat was 200 and 73% when it was 350 cells/mm(3). Independent risk factors for not being treated during CHI despite meeting the criteria were lower viral load, lower educational level, and poorer living conditions. CONCLUSION: HIV ART initiation guidelines are largely followed by practitioners in France. What can still be improved, however, is time to treat when CD4 cell counts reach the threshold to treat. Risk factors for lack of timely treatment highlight the need to understand better how patients' living conditions and physicians' perceptions influence the decision to initiate treatment

Hand-Assisted laparoscopic donor nephrectomy PERiumbilical versus Pfannenstiel incision and return to normal physical ACTivity (HAPERPACT): study protocol for a randomized controlled trial

Background: Hand-assisted laparoscopic living donor nephrectomy (HALDN) using a periumbilical or Pfannenstiel incision was developed to improve donor outcome after a kidney transplant. The aim of this study was to investigate two methods of hand assistance and kidney removal during HALDN and their effect on the time it takes for the donor to return to normal physical activity. Methods/design: This study was initiated in November 2017 and is expected to last for 2 years. To be eligible for the study, donors must be more than 20 years of age and must not be receiving permanent pain therapy. Only donors with a single artery and vein in the graft are being enrolled in this trial. Donors with infections or scars in the periumbilical or hypogastric area, bleeding disorders, chronic use of immunosuppressive agents, or active infection will be excluded. Donors will be randomly allocated to either a control arm (periumbilical incision) or an intervention arm (Pfannenstiel incision). The sample size was calculated as 26 organ donors in each group. The primary endpoint is the number of days it takes the donor to return to normal physical activity (up to 4 weeks after the operation). Secondary endpoints are intraoperative outcomes, including estimated blood loss, warm ischemia time, and duration of the operation. Postoperative pain will be assessed using the visual analog scale, rescue analgesic use, and peak expiratory flow rate. Length of hospital stay, physical activity score, time to return to work, donor satisfaction, cosmetic score, postoperative complications, and all-cause mortality in living donors will also be reported. Delayed graft function, primary non-function, serum creatinine levels, and glomerular filtration rate will also be assessed in the recipients after transplantation. Discussion: This is the first randomized controlled trial to compare the time it takes the living donor to return to normal physical activity after HALDN using two different types of incision. The comprehensive findings of this study will help decide which nephrectomy procedure is best for living donors with regard to patient comfort and satisfaction as well as graft function in the recipient after transplantation. Trial registration: ClinicalTrials.gov, NCT03317184 . Registered on 23 October 2017

Between ritual and everyday : musicking, virtue ethics, and politics in diasporic Persian-speaking churches

After the Islamic Revolution of 1979 in Iran, the theocratic state regulated and controlled emotions in the country due to religious-nationalism and anti-colonialism discourses. The regime suppressed joyful activities, coercing people into sadness. For these reasons, scholarship on music, politics, and affect in Iran have argued that the expression of joy serves as a subversive act and resistance against the state-promoted sadness. Building on this scholarly foundation, this dissertation explores the spiritual and political works of joy (shādi) among diasporic Persian-speaking Christians by analyzing their musical practices. Members of these diasporic churches who have converted from Islam to Christianity are immigrants and refugees who left Iran the years after the Revolution. As such, these Christians are in-between multiple states such as living as Muslim or Christian, living in a permanent or temporarily diasporic state, and fusing Persian and Western European musical practices to ground their experiences of in-betweenness. I conducted multi-sited and hybrid ethnographic research among Persian-speaking Christians in cities of Los Angeles, Austin, Dallas, and Stockholm during 2021-2024. My fieldwork revealed daily and ritual practices of shādi as an ethical affect through textual forms such as sermons, Bible verses, song lyrics, and the paratextual 6/8 dance rhythm. I argue that Persian-speaking Christians’ musicking at church is an ethical and affective practice, through which the community and individuals understand themselves as spiritual and political beings. Drawing on interdisciplinary perspectives from ethnomusicology, ritual and practice theories, affect theory, ethics, and the politics of music in Iran and its diaspora, I illustrate how repeated communal acts of musicking establish and maintain pious subjects. I assert that through musicking, this Christian community not only shapes their pious subjectivity but also navigates and surmounts the in-between political and social conditions of living in the diaspora.Musi