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101.
102.
Suzanne M Jan de Beur Paul D Miller Thomas J Weber Munro Peacock Karl Insogna Rajiv Kumar Frank Rauch Diana Luca Tricia Cimms Mary Scott Roberts Javier San Martin Thomas O Carpenter 《Journal of bone and mineral research》2021,36(4):627-635
Tumor-induced osteomalacia (TIO) is caused by phosphaturic mesenchymal tumors producing fibroblast growth factor 23 (FGF23) and is characterized by impaired phosphate metabolism, skeletal health, and quality of life. UX023T-CL201 is an ongoing, open-label, phase 2 study investigating the safety and efficacy of burosumab, a fully human monoclonal antibody that inhibits FGF23, in adults with TIO or cutaneous skeletal hypophosphatemia syndrome (CSHS). Key endpoints were changes in serum phosphorus and osteomalacia assessed by transiliac bone biopsies at week 48. This report focuses on 14 patients with TIO, excluding two diagnosed with X-linked hypophosphatemia post-enrollment and one with CSHS. Serum phosphorus increased from baseline (0.52 mmol/L) and was maintained after dose titration from week 22 (0.91 mmol/L) to week 144 (0.82 mmol/L, p < 0.0001). Most measures of osteomalacia were improved at week 48: osteoid volume/bone, osteoid thickness, and mineralization lag time decreased; osteoid surface/bone surface showed no change. Of 249 fractures/pseudofractures detected across 14 patients at baseline, 33% were fully healed and 13% were partially healed at week 144. Patients reported a reduction in pain and fatigue and an increase in physical health. Two patients discontinued: one to treat an adverse event (AE) of neoplasm progression and one failed to meet dosing criteria (receiving minimal burosumab). Sixteen serious AEs occurred in seven patients, and there was one death; all serious AEs were considered unrelated to treatment. Nine patients had 16 treatment-related AEs; all were mild to moderate in severity. In adults with TIO, burosumab exhibited an acceptable safety profile and was associated with improvements in phosphate metabolism and osteomalacia. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.. 相似文献
103.
Carlos Solano Lourdes Vázquez Estela Giménez Rafael de la Cámara Eliseo Albert Montserrat Rovira Ildefonso Espigado Carmen M. Calvo Javier López-Jiménez María Suárez-Lledó Anabella Chinea Albert Esquirol Ariadna Pérez Aránzazu Bermúdez Raquel Saldaña Inmaculada Heras Ana J. González-Huerta Tamara Torrado Guiomar Bautista Montserrat Batlle Santiago Jiménez Carlos Vallejo Pere Barba María Á. Cuesta José L. Piñana David Navarro 《American journal of transplantation》2021,21(1):258-271
The net impact of cytomegalovirus (CMV) DNAemia on overall mortality (OM) and nonrelapse mortality (NRM) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a matter of debate. This was a retrospective, multicenter, noninterventional study finally including 749 patients. CMV DNA monitoring was conducted by real-time polymerase chain reaction (PCR) assays. Clinical outcomes of interest were OM and NRM through day 365 after allo-HSCT. The cumulative incidence of CMV DNAemia in this cohort was 52.6%. A total of 306 out of 382 patients with CMV DNAemia received preemptive antiviral therapy (PET). PET use for CMV DNAemia, but not the occurrence of CMV DNAemia, taken as a qualitative variable, was associated with increased OM and NRM in univariate but not in adjusted models. A subcohort analysis including patients monitored by the COBAS Ampliprep/COBAS Taqman CMV Test showed that OM and NRM were comparable in patients in whom either low or high plasma CMV DNA threshold (<500 vs ≥500 IU/mL) was used for PET initiation. In conclusion, CMV DNAemia was not associated with increased OM and NRM in allo-HSCT recipients. The potential impact of PET use on mortality was not proven but merits further research. 相似文献
104.
Cathy Logan Ily Yumul Javier Cepeda Victor Pretorius Eric Adler Saima Aslam Natasha K. Martin 《American journal of transplantation》2021,21(2):657-668
Outcomes following hepatitis C virus (HCV)-viremic heart transplantation into HCV-negative recipients with HCV treatment are good. We assessed cost-effectiveness between cohorts of transplant recipients willing and unwilling to receive HCV-viremic hearts. Markov model simulated long-term outcomes among HCV-negative patients on the transplant waitlist. We compared costs (2018 USD) and health outcomes (quality-adjusted life-years, QALYs) between cohorts willing to accept any heart and those willing to accept only HCV-negative hearts. We assumed 4.9% HCV-viremic donor prevalence. Patients receiving HCV-viremic hearts were treated, assuming $39 600/treatment with 95% cure. Incremental cost-effectiveness ratios (ICERs) were compared to a $100 000/QALY gained willingness-to-pay threshold. Sensitivity analyses included stratification by blood type or region and potential negative consequences of receipt of HCV-viremic hearts. Compared to accepting only HCV-negative hearts, accepting any heart gained 0.14 life-years and 0.11 QALYs, while increasing costs by $9418/patient. Accepting any heart was cost effective (ICER $85 602/QALY gained). Results were robust to all transplant regions and blood types, except type AB. Accepting any heart remained cost effective provided posttransplant mortality and costs among those receiving HCV-viremic hearts were not >7% higher compared to HCV-negative hearts. Willingness to accept HCV-viremic hearts for transplantation into HCV-negative recipients is cost effective and improves clinical outcomes. 相似文献
105.
Aránzazu Caballero-Marcos Magdalena Salcedo Roberto Alonso-Fernández Manuel Rodríguez-Perálvarez María Olmedo Javier Graus Morales Valentín Cuervas-Mons Alba Cachero Carmelo Loinaz-Segurola Mercedes Iñarrairaegui Lluís Castells Sonia Pascual Carmen Vinaixa-Aunés Rocío González-Grande Alejandra Otero Santiago Tomé Javier Tejedor-Tejada José María Álamo-Martínez Luisa González-Diéguez Flor Nogueras-Lopez Gerardo Blanco-Fernández Gema Muñoz-Bartolo Francisco Javier Bustamante Emilio Fábrega Mario Romero-Cristóbal Rosa Martin-Mateos Julia Del Rio-Izquierdo Ana Arias-Milla Laura Calatayud Alberto A. Marcacuzco-Quinto Víctor Fernández-Alonso Concepción Gómez-Gavara Jordi Colmenero Patricia Muñoz José A. Pons the Spanish Society of Liver Transplantation 《American journal of transplantation》2021,21(8):2876-2884
The protective capacity and duration of humoral immunity after SARS-CoV-2 infection are not yet understood in solid organ transplant recipients. A prospective multicenter study was performed to evaluate the persistence of anti-nucleocapsid IgG antibodies in liver transplant recipients 6 months after coronavirus disease 2019 (COVID-19) resolution. A total of 71 liver transplant recipients were matched with 71 immunocompetent controls by a propensity score including variables with a well-known prognostic impact in COVID-19. Paired case–control serological data were also available in 62 liver transplant patients and 62 controls at month 3 after COVID-19. Liver transplant recipients showed a lower incidence of anti-nucleocapsid IgG antibodies at 3 months (77.4% vs. 100%, p < .001) and at 6 months (63.4% vs. 90.1%, p < .001). Lower levels of antibodies were also observed in liver transplant patients at 3 (p = .001) and 6 months (p < .001) after COVID-19. In transplant patients, female gender (OR = 13.49, 95% CI: 2.17–83.8), a longer interval since transplantation (OR = 1.19, 95% CI: 1.03–1.36), and therapy with renin–angiotensin–aldosterone system inhibitors (OR = 7.11, 95% CI: 1.47–34.50) were independently associated with persistence of antibodies beyond 6 months after COVID-19. Therefore, as compared with immunocompetent patients, liver transplant recipients show a lower prevalence of anti-SARS-CoV-2 antibodies and more pronounced antibody levels decline. 相似文献
106.
Lennart Berglin Peter Gouras Yoahua Sheng Javier Lavid Po-Kang Lin Huiyun Cao Hild Kjeldbye 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》1997,235(2):103-110
Background: RPE transplantation offers the possibility of treating certain forms of retinal degeneration. Understanding how to optimize the surgical technique for performing RPE transplantation, especially in primates, is therefore of considerable interest. Methods: Fifteen patch RPE transplants were performed in six monkeys. The transplant sites were examined at follow-up by ophthalmoscopy, biomicroscopy, fluorescein angiography and histology. Foveal and peripheral retinal transplants were compared. Results: Human fetal RPE xenografts can survive without rejection for at least 6 months after transplantation in monkey retina. Such grafts form a basal lamina and make intimate contacts with the outer segments of the host. Both rods and cones retain a normal appearance when in contact with unrejected transplants. Rejection occurred in only 30% (3/10) of the peripheral but in 60% (3/5) of the foveal transplants. Conclusions: Cultured human fetal RPE patch transplants can survive and maintain local photoreceptor integrity for relatively long periods of time in monkey subretinal space without immunosuppression. Rejection, when it occurs, is more frequent near the fovea. 相似文献
107.
108.
Blanco JA Javier G Fraile M Isnard RM Castellví A López P Riba J Prats J Casasa JM 《Cirugía pediátrica : organo oficial de la Sociedad Espa?ola de Cirugía Pediátrica》1999,12(3):127-128
Radio-guided surgery is a new technique which can provide benefits for pediatric oncology, as in our patient with neuroblastoma in stage IV, that after a chemotherapy, surgical, radiotherapy and autologous bone marrow transplant treatment kept showing, at 2 years, residual tumoral fragments and increase of catecholamines. Radio-guided surgery allowed an easy and exact location. This technique decreases surgery time and let us find residual tumoral tissue no matter how small. With radio-guided surgery we can obtain higher survival and even cure the patient. 相似文献
109.
Professor Jose L. Balibrea M.D. Jose Gomez M.D. Jose R. Alemany M.D. Jose Aznar M.D. Mercedes Canela M.D. Enrique Castells M.D. Jose L. Fernandez M.D. Pedro G. Barreno M.D. Javier Ruiz M.D. 《World journal of surgery》1980,4(1):83-89
The purpose of these experiments was to study the incidence of stress ulcers in restrained rats and to correlate it with hypothalamic and adrenal cortical and medullary activity, with and without vagotomy. A total of 217 adult rats were used, grouped into 56 sets, and distributed at random in 5 experimental groups. Restraint was followed by a 79% incidence of ulceration in the glandular portion of the gastric mucosa. Vagotomy made these worse (p<0.01). Hypothalamic levels of catecholamines and serotonin showed no significant changes. Urinary measurements revealed decreased excretion of 17-ketosteroids (p<0.001), increased excretion of uropepsinogen (p<0.01), and no significant changes in vanillylmandelic acid among the rats submitted to immobilization. In the adrenal glands of stressed animals, there was a decreased level of catecholamines (p<0.01) and no significant changes in corticosteroid content (17-ketosteroids). These results suggest that hypothalamic stimulation and the participation of the adrenal glands are not essential factors in the pathogenesis of restraint-induced experimental stress ulcer. 相似文献
110.
Summary Reactive microglia in the developing brain after stab wound was studied by morphological, cytochemical, and autoradiographic methods. Morphologically, early reactive cells are of the M cell type (Matthews 1974). They show an activated nucleus, cytoplasm rich in ribosomes with wide Golgi complex and variable numbers of lipid inclusions. Big clear vacuoles are found in many of these cells. Microtubules not associated with centrioles and filaments may or may not be present. Junctional complexes of the zonula or puncta adherentia types are occasionally found. Strong NADPH dehydrogenase, weak NADH dehydrogenase, strong ATPase, and strong acid phosphatase, in addition to nonspecific esterase activites were demonstrated in many reactive cells. Intravenous infusion of labelled bone marrow cells from a donor showed labelled macrophages and labelled perivascular cells at the site of injury. Intracerebral injection of a small dose of tritiated thymidine at the time of injury resulted in the appearance of labelled macrophages in the following days. These data suggest that many of the reactive cells have an exogenous, more probably monocytic, origin; but a certain amount of endogenous cells also act as macrophages in brain injuries. 相似文献