2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology ...
Parents Search For 'hero' Kidney Donor For 2-year-old Boy
A 2-year-old boy who beat the odds by surviving a very rare birth defect is now in search of a "hero" kidney donor to save his life again.
"They are out there living their life right now, and they are his perfect match, and one day ... They're going to come forward and donate their kidney to Conrad," Austyn Evans, 2-year-old Conrad's mom, told "Good Morning America." "And it's just such an amazing thing to think that my child's hero is walking around in the world."
Conrad, whom Evans shares with her husband Branden Williams, was born with a rare birth defect known as lower urinary tract obstruction, or LUTO, which impacts his kidneys and bladder. The condition, which affects only 1 in every 5,000 to 7,0000 births, prevents the passage of urine, which can lead to kidney damage, and can impair fetal lung development, according to the Children's Hospital of Philadelphia.
In Conrad's case, the drainage portion of his kidney was not developed correctly at birth, which resulted in end-stage kidney disease, which is a nearly one-in-a-million condition in infants, according to Dr. Joshua Zaritsky, a pediatric nephrologist at Studer Family Children's Hospital at Ascension Sacred Heart in Pensacola, Florida, and the doctor currently overseeing Conrad's care.
Evans said she learned of her son's rare birth defect while she was pregnant. She and her husband moved from Florida to Houston when Evans was in her third trimester so they could receive specialty care at Texas Children's Hospital.
Conrad spent the first six months of his life in the neonatal intensive care unit, or NICU, at Texas Children's Hospital, where he was placed on a ventilator immediately after birth and subsequently spent hours each day connected to a state-of-the-art dialysis machine specially designed for infants.
Baby Conrad spent the first six months of his life in the NICU at Texas Children's Hospital.
Austyn Evans/Texas Children's Hospital
When he was discharged from the NICU last June, Evans and her husband became the primary caregivers for Conrad, connecting him to a dialysis machine at home each night and maintaining the gastrostomy tube, or G-tube, that gives him medication and nutrition directly to his stomach.
"Conrad is on dialysis eight hours every single night, and in addition to that, we do his blood pressure and we do his weight and his temperature twice daily," Evans said. "He takes over 13 medications because dialysis doesn't work like a kidney works ... We have to give him supplemental medication to keep him well and growing and thriving."
Due to the catheter used for dialysis, Conrad cannot take a bath or get wet, and has to stay especially clean, meaning he can't play outside and get messy like a typical 2-year-old, according to Evans.
"It's very hard to tell a toddler, 'No,'" Evans said of the limitations her son faces. "I would say that his childhood is continually being robbed from him."
Conrad Evans, 2, is in need of a kidney donor due to a rare birth defect.
Austyn Evans
Since his birth, doctors have said that Conrad would be in need of a kidney transplant in order to stay alive, according to Evans. She and her husband and other family members were not matches for Conrad, so for more than a year, the family has searched for the right stranger to donate a kidney to Conrad.
"The need for Conrad to get a kidney is pretty immediate," Evans said. "We continue to see his little body give us signs that dialysis isn't giving the best filtration. His growth and development are two of the things that we see a lot of suffering in while he's on dialysis."
MORE: Woman finds kidney donor through TikTokConrad, who turned 2 in December, is in need of a kidney from an adult living donor both because a living donor's kidney will provide more longevity, and because a living donor allows for more time for planning for the transplant, according to Zaritsky.
Austyn Evans and Branden Williams pose with their son, Conrad, who is in need of a kidney transplant.
Austyn Evans
Research shows that a kidney from a living donor will last five to 10 years longer than a kidney from a deceased donor. In addition, the waiting time for an organ for a deceased donor can be multiple years, time that a child in Conrad's situation does not have.
"For the most part, the majority of kids who receive an organ get an adult organ," Zaritsky told "GMA," noting that with a kidney transplant, its easier to work with an adult kidney than a pediatric kidney. "If you look at the donor list, pediatric patients are sort of given preference for the highest-quality kidneys because we as a society have decided that they, children, are going to get the most bang for the buck for a kidney transplant and we're going to try to prioritize them for the best kidneys on the list."
A kidney transplant surgery typically takes three to four hours and involves two operations, one to remove the kidney from the donor and another to place the donated kidney in the recipient. Both the kidney donor and the recipient typically stay in the hospital for "several days" following the transplant, according to the National Institutes of Health.
Best friend couples donate kidneys to each other
High school teacher getting ready to donate kidney to student
Woman saves man's life, then his daughter's life 6 years later
Zaritsky said that for a young patient like Conrad, his health would improve immediately after transplant. In addition to no longer needing to be on dialysis, Zaritsky said a kidney transplant would help improve everything from Conrad's eyes to his ability to grow and speak and be independent.
"Imagine a donation where you're potentially increasing that person's lifespan," he said. "You're doubling that person's lifespan and, in some cases, tripling it."
Austyn Evans and Branden Williams pose with their son, Conrad, who is in need of a kidney transplant.
Austyn Evans
Evans said she hopes that sharing her family's story helps raise awareness of not only Conrad's need for a kidney donor, but of the larger need for organ donors across the United States.
Currently, over 103,000 children and adults are on the national transplant waiting list, and 17 people die each day waiting for an organ donation, according to the U.S. Health and Resources Administration.
MORE: After their dad died in need of a kidney transplant, 2 sisters donate their kidneys to strangersAccording to Evans, one of the most challenging parts of searching for a donor for Conrad has been educating people that he, like many kids on the transplant waiting list, needs an adult kidney.
"Throughout this search, I can't tell you the number of people who have reached out and said, 'I wish I could donate. I'm an adult, though. My kidney will be too big,'" she said. "There's just not this realization that an adult donor is exactly what Conrad needs in order to [have] a kidney transplant."
Conrad Evans, 2, is in need of a kidney donor due to a rare birth defect.
Austyn Evans
Evans continued, "The best kidney that we can get Conrad right now sets him up for a long and full life that's not full of hospital admissions consistently, or searching for a donor multiple times."
Shortly after Conrad's birth, Evans started a Facebook page to share information on how to apply to be a donor because she said she wants his story shared far and wide.
"You never know where Conrad's hero is," Evans said. "The more people that this can reach, the greater chance we have of saving Conrad."
Fetal And Neonatal Lung Development
Crossref Citations
This Book has been cited by the following publications. This list is generated based on data provided by Crossref.van Well, Gijs T. J. Daalderop, Leonie A. Wolfs, Tim and Kramer, Boris W. 2017. Human perinatal immunity in physiological conditions and during infection. Molecular and Cellular Pediatrics, Vol. 4, Issue. 1,
Schachner, E. R. Sedlmayr, J. C. Schott, R. Lyson, T. R. Sanders, R. K. And Lambertz, M. 2017. Pulmonary anatomy and a case of unilateral aplasia in a common snapping turtle (Chelydra serpentina): developmental perspectives on cryptodiran lungs. Journal of Anatomy, Vol. 231, Issue. 6, p. 835.
Agustí, Alvar and Celli, Bartolomé 2017. Natural history of COPD: gaps and opportunities. ERJ Open Research, Vol. 3, Issue. 4, p. 00117-2017.
Breyer-Kohansal, Robab Hartl, Sylvia Burghuber, Otto Chris Urban, Matthias Schrott, Andrea Agusti, Alvar Sigsgaard, Torben Vogelmeier, Claus Wouters, Emiel Studnicka, Michael and Breyer, Marie-Kathrin 2019. The LEAD (Lung, Heart, Social, Body) Study: Objectives, Methodology, and External Validity of the Population-Based Cohort Study. Journal of Epidemiology, Vol. 29, Issue. 8, p. 315.
Laughney, Ashley M. Hu, Jing Campbell, Nathaniel R. Bakhoum, Samuel F. Setty, Manu Lavallée, Vincent-Philippe Xie, Yubin Masilionis, Ignas Carr, Ambrose J. Kottapalli, Sanjay Allaj, Viola Mattar, Marissa Rekhtman, Natasha Xavier, Joao B. Mazutis, Linas Poirier, John T. Rudin, Charles M. Pe'er, Dana and Massagué, Joan 2020. Regenerative lineages and immune-mediated pruning in lung cancer metastasis. Nature Medicine, Vol. 26, Issue. 2, p. 259.
Decrue, Fabienne Gorlanova, Olga Usemann, Jakob and Frey, Urs 2020. Lung functional development and asthma trajectories. Seminars in Immunopathology, Vol. 42, Issue. 1, p. 17.
Amatya, Shaili Rajbhandari, Sharina Pradhan, Sandeep Trinh, Van Paudel, Umesh and Parton, Lance A. 2021. Hedgehog signaling pathway gene variant influences bronchopulmonary dysplasia in extremely low birth weight infants. World Journal of Pediatrics, Vol. 17, Issue. 3, p. 298.
Gruzieva, Olena Jeong, Ayoung He, Shizhen Yu, Zhebin de Bont, Jeroen Pinho, Maria G.M. Eze, Ikenna C. Kress, Sara Wheelock, Craig E. Peters, Annette Vlaanderen, Jelle de Hoogh, Kees Scalbert, Augustin Chadeau-Hyam, Marc Vermeulen, Roel C.H. Gehring, Ulrike Probst-Hensch, Nicole and Melén, Erik 2022. Air pollution, metabolites and respiratory health across the life-course. European Respiratory Review, Vol. 31, Issue. 165, p. 220038.
Dassios, Theodore 2023. Critical functional lung volumes in neonatal intensive care: evidence and clinical applications. Pediatric Research, Vol. 94, Issue. 1, p. 82.
How Immune Cells Shape Our Earliest Breaths
In a recent study published in the journal Science Immunology, researchers profile the origins and subsequent differentiation of embryonic and fetal immune cells during human lung development.
Study: Early human lung immune cell development and its role in epithelial cell fate. Image Credit: u3d / Shutterstock.Com
Previous research has extensively documented the functions of immune cells in regeneration, maintaining homeostasis, particularly in the intestine and testis, and somatic tissue development. Studies have aimed to elucidate the structure, subtypes, and function of epithelial and mesenchymal cells; however, a gap exists in researchers' understanding of the processes and functional roles of lung immune cells.
Immune cells are some of the most critical cells responsible for an infant's survival from birth onwards. Given the defenses provided by lung-associated mucosal immune cells against airborne pathogens and inhaled toxins, the current dearth of literature on the subject is surprising. A possible explanation for this gap in the literature may be due to the complex nature of cell differentiation during embryonic development and the historical lack of techniques capable of safely tracing these differentiations throughout pregnancy.
A critical question that remains unanswered is whether immune cells might have functions over and above defense – could they modulate or otherwise influence the development of the tissues wherein they reside? Answering this and similar questions pertaining to human lung development at both cellular and molecular levels may result in the genesis of novel clinical interventions designed to repair and regenerate lungs, thereby affording millions or even hundreds of millions of patients an alternative to lung transplantation.
Previous research has characterized human lung developmental morphology and classified the process into five temporally overlapping stages. These consist of the embryonic stage between four and seven weeks post conception (pcw), the pseudoglandular stage between five and 17 pcw, the canalicular stage between 16 and 26 pcw, the saccular stage between 24 and 38 pcw, and the alveolar stage from 36 pcw to 21 years of age.
The first three stages, specifically between five and 22 pcw, represent the least understood period of lung development despite their collectively covering the entire evolution of epithelial stem cells into almost functional lungs.
About the studyThe present study aimed to evaluate the temporal progression of the fetal immune system and elucidate its potential role in modulating embryonic lung development. Human fetal and embryonic samples were acquired from the Human Developmental Biology Resource (HDBR) Joint MRC/Wellcome Trust grant.
Pregnancies terminated between five and 22 pcw were used to obtain fresh lung tissue with written consent from donors. Karyotypic analysis was performed to ensure that included samples were free from genetic abnormalities and represented 'typical' human embryonic growth.
Immunohistochemistry (IHC) of lung tissues was used to validate immune cell types and quantity across the first three stages of embryonic lung development. IHC analysis further contributed to evaluating the locations of observed immune cells and variations therein from five to 22 pcw.
To improve the accuracy and reliability of immune cell quantification, three-dimensional (3D) quantification using confocal microscopy followed by Imaris software analyses was performed. Computed 3D images were compared to 2D images at every time point across the study duration.
Lung tissue digestion followed by flow cytometry and fluorescence-activated cell sorting (FACS) were used to validate IHC quantification estimates, elucidate relative proportions of CD3+, CD4+, CD8+, and regulatory T cells (Tregs) as a proportion of CD45+ populations for the same developmental stage, and sort CD45+ cells as a precursor to single-cell ribonucleic acid (RNA) sequencing (scRNA-sq).
Moreover, scRNA-sq served the dual purpose of validating flow cytometry results and the molecular characterization of immune cells across samples. Cellular indexing of transcriptomes and epitopes sequencing (CITE-seq) was additionally employed to improve the resolution of the results.
Human embryonic lung organoids were also used for functional characterization experiments, including cytokine treatments, dual Suppressor of Mothers Against Decapentaplegic (SMAD) transcription assays, and macrophage, dendritic cell (DC) culture, and cytokine arrays.
All obtained data were subject to statistical analyses consisting of one-way Analysis of Variance (ANOVA), unpaired two-tailed t-tests, residual maximum likelihood analysis (REML), and Tukey's post hoc multiple-comparison test.
Study findingsThe scRNA-seq, IHC, and functional organoid assays revealed that immune cell populations varied significantly across fetal developmental stages. Progenitor and innate immune cells, including myeloid, innate lymphoid (ILC), and natural killer (NK) cells, predominated in early developmental stages but were gradually replaced by T- and B-lymphocytes. CD45+ cells were nearly ubiquitous across developmental stages and in all lung-associated tissue regions; however, their relative quantity varied across time and location.
Molecular characterization of immune cells revealed 77,559 transcriptomic profiles, 61,757 of which are novel to science. Annotation of these profiles followed by clustering analyses revealed 59 clusters representative of all known immune cell categories. Analyses of the progenitors of these categories resulted in the discovery of unexpectedly high ILC- and early lymphoid progenitor (ELPs) densities.
Taken together, these results suggest that immune cells follow a biphasic pattern during fetal development and a spike in abundance during eight and 20 pcw. Quantitivate polymerase chain reaction (qPCR) evaluations suggest that the 20 pcw peak may be partially due to vascular maturation.
B-cell maturation in lungs was revealed for the first time using IHC and single-molecule fluorescence in situ hybridization (smFISH) assays. This added to a growing body of evidence that the bone marrow is not the sole source of mature B-cells, which is contrary to previous scientific beliefs.
Immunoglobulin (Ig) isotype expression in tandem with clonal expansion assays revealed that, during development, lung mesenchyme and epithelium support B-cell homeostasis through the secretion of modulatory chemokines, including CCL28.
The collective output of transcriptomic and cytokine assays revealed the complex interactions of multiple immune cell-secreted cytokines, which, in turn, were functionally validated to affect epithelial cell differentiation. These results suggest that immune cells serve a dual purpose of defense and lung development during fetal development, thereby confirming previous hypotheses.
ConclusionsIn the present study, researchers combined cutting-edge transcriptomic analyses with IHC to elucidate immune cells' structural and functional roles during fetal and embryonic development. Evaluations of fetal immune cells during the five to 33 pcw period revealed that complete B-cell maturation occurs in embryonic lungs, which contests the prevalent belief that the bone marrow is the sole source of mature B-cell populations.
Interleukin-1 beta (IL-1β) was found to be extensively produced by widely dispersed myeloid cells. IL-1β, in turn, was found to modulate and promote epithelial stem cell differentiation, highlighting the dual role of immune cells in both defense and lung epithelial development.
Together, these findings provide an immune atlas of developing human lungs and suggest a role for fetal immune cells in guiding development of the lung epithelium."
Journal reference:
Comments
Post a Comment