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1.
Cell ; 178(4): 795-806.e12, 2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31398337

RESUMO

Most patients diagnosed with resected pancreatic adenocarcinoma (PDAC) survive less than 5 years, but a minor subset survives longer. Here, we dissect the role of the tumor microbiota and the immune system in influencing long-term survival. Using 16S rRNA gene sequencing, we analyzed the tumor microbiome composition in PDAC patients with short-term survival (STS) and long-term survival (LTS). We found higher alpha-diversity in the tumor microbiome of LTS patients and identified an intra-tumoral microbiome signature (Pseudoxanthomonas-Streptomyces-Saccharopolyspora-Bacillus clausii) highly predictive of long-term survivorship in both discovery and validation cohorts. Through human-into-mice fecal microbiota transplantation (FMT) experiments from STS, LTS, or control donors, we were able to differentially modulate the tumor microbiome and affect tumor growth as well as tumor immune infiltration. Our study demonstrates that PDAC microbiome composition, which cross-talks to the gut microbiome, influences the host immune response and natural history of the disease.


Assuntos
Carcinoma Ductal Pancreático/microbiologia , Carcinoma Ductal Pancreático/mortalidade , Microbioma Gastrointestinal , Neoplasias Pancreáticas/microbiologia , Neoplasias Pancreáticas/mortalidade , Adulto , Idoso , Animais , Bactérias/classificação , Linhagem Celular Tumoral , Estudos de Coortes , Transplante de Microbiota Fecal , Fezes/microbiologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Análise de Sequência de RNA , Taxa de Sobrevida
2.
Bioessays ; : e2400118, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39058892

RESUMO

Parkinson's disease (PD) is characterized by the loss of the dopaminergic nigrostriatal pathway which has led to the successful development of drug therapies that replace or stimulate this network pharmacologically. Although these drugs work well in the early stages of the disease, over time they produce side effects along with less consistent clinical benefits to the person with Parkinson's (PwP). As such there has been much interest in repairing this pathway using transplants of dopamine neurons. This work which began 50 years ago this September is still ongoing and has now moved to first in human trials using human pluripotent stem cell-derived dopaminergic neurons. The results of these trials are eagerly awaited although proof of principle data has already come from trials using human fetal midbrain dopamine cell transplants. This data has shown that developing dopamine cells when transplanted in the brain of a PwP can survive long term with clinical benefits lasting decades and with restoration of normal dopaminergic innervation in the grafted striatum. In this article, we discuss the history of this field and how this has now led us to the recent stem cell trials for PwP.

3.
Circulation ; 147(6): 482-497, 2023 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-36515099

RESUMO

BACKGROUND: Transplant arteriosclerosis is a major complication in long-term survivors of heart transplantation. Increased lymph flow from donor heart to host lymph nodes has been reported to play a role in transplant arteriosclerosis, but how lymphangiogenesis affects this process is unknown. METHODS: Vascular allografts were transplanted among various combinations of mice, including wild-type, Lyve1-CreERT2;R26-tdTomato, CAG-Cre-tdTomato, severe combined immune deficiency, Ccr2KO, Foxn1KO, and lghm/lghdKO mice. Whole-mount staining and 3-dimensional reconstruction identified lymphatic vessels within the grafted arteries. Lineage tracing strategies delineated the cellular origin of lymphatic endothelial cells. Adeno-associated viral vectors and a selective inhibitor were used to regulate lymphangiogenesis. RESULTS: Lymphangiogenesis within allograft vessels began at the anastomotic sites and extended from preexisting lymphatic vessels in the host. Tertiary lymphatic organs were identified in transplanted arteries at the anastomotic site and lymphatic vessels expressing CCL21 (chemokine [C-C motif] ligand 21) were associated with these immune structures. Fibroblasts in the vascular allografts released VEGF-C (vascular endothelial growth factor C), which stimulated lymphangiogenesis into the grafts. Inhibition of VEGF-C signaling inhibited lymphangiogenesis, neointima formation, and adventitial fibrosis of vascular allografts. These studies identified VEGF-C released from fibroblasts as a signal stimulating lymphangiogenesis extending from the host into the vascular allografts. CONCLUSIONS: Formation of lymphatic vessels plays a key role in the immune response to vascular transplantation. The inhibition of lymphangiogenesis may be a novel approach to prevent transplant arteriosclerosis.


Assuntos
Arteriosclerose , Transplante de Coração , Vasos Linfáticos , Camundongos , Animais , Humanos , Linfangiogênese , Fator C de Crescimento do Endotélio Vascular/genética , Fator C de Crescimento do Endotélio Vascular/metabolismo , Fator C de Crescimento do Endotélio Vascular/farmacologia , Transplante de Coração/efeitos adversos , Células Endoteliais/metabolismo , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Doadores de Tecidos , Vasos Linfáticos/patologia , Arteriosclerose/metabolismo
4.
Am J Transplant ; 24(3): 479-490, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37898317

RESUMO

During the pandemic period, health care systems were substantially reorganized for managing COVID-19 cases. Corresponding consequences on persons with chronic diseases remain insufficiently documented. This observational cohort study investigated the direct and indirect impact of the pandemic period on the survival of kidney transplant recipients (KTR). Using the French National Health Data System, incident persons with end-stage kidney disease between 2015 and 2020, and who received a kidney transplant during this period were included and followed up from their transplantation date to December 31, 2021. The survival of KTR during the prepandemic and pandemic periods was investigated using Cox models with time-dependent covariates. There were 10 637 KTR included in the study, with 324 and 430 deaths observed during the prepandemic and pandemic periods, respectively. The adjusted risk of death during the pandemic period was similar to that observed during the prepandemic period (hazard ratio [HR] [95% confidence interval]: 0.92 [0.77-1.11]), COVID-19-related hospitalization was associated with an increased risk of death (HR: 10.62 [8.46-13.33]), and a third vaccine dose was associated with a lower risk of death (HR: 0.42 [0.30-0.57]). The pandemic period was not associated with an indirect higher risk of death in KTR with no COVID-19-related hospitalization.


Assuntos
COVID-19 , Transplante de Rim , Humanos , COVID-19/epidemiologia , Pandemias , Transplantados , França/epidemiologia
5.
World J Urol ; 42(1): 116, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38436781

RESUMO

PURPOSE: Successful treatment options for ureteral strictures are limited. Surgical options such as ileal interposition and kidney autotransplantation are difficult and associated with morbidity and complications. Techniques such as Boari flap and psoas hitch are limited to distal strictures. Only limited case studies on the success of open buccal mucosa graft (BMG) ureteroplasty exist to this date. The purpose of this study was to evaluate the success of open BMG ureteroplasty without omental wrap. METHODS: In this single-center retrospective study between July 2020 and January 2023, we included 14 consecutive patients with ureteric strictures who were treated with open BMG ureteroplasty without omental wrap. The primary outcome was the success of open BMG ureteroplasty. Further endpoints were complications and hospital readmission. Outcome variables were assessed by clinical examination, kidney sonography, and patient anamnesis. RESULTS: Out of 14 patients, 13 were stricture and ectasia-free without a double-J stent at a median follow-up of 15 months (success rate 93%). No complications were observed at the donor site, and the complication rate overall was low with 3 out of 14 patients (21%) having mild-to-medium complications. CONCLUSIONS: Open BMG ureteroplasty without omental wrap is a successful and feasible technique for ureteric stricture repair.


Assuntos
Mucosa Bucal , Procedimentos de Cirurgia Plástica , Humanos , Constrição Patológica/cirurgia , Estudos Retrospectivos , Rim
6.
Eur J Haematol ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39135216

RESUMO

BACKGROUND: Graft-versus-host disease (GVHD) is a recognized complication among individuals undergoing bone marrow transplantation (BMT). There is a requirement for supplementary data regarding the in-patient outcomes of GVHD in individuals who have undergone BMT. Our analysis seeks to assess the healthcare burden and outcomes associated with GVHD in hospitalized patients who have undergone BMT. METHOD: In this retrospective study, we used data from the National Inpatient Sample (NIS) database spanning from 2016 to 2019. Utilizing ICD-10 codes, we distinguished hospitalizations related to BMT and grouped them into two categories: those with GVHD and those without GVHD. Our areas of focus included in-hospital mortality, length of stay, charges, and associations related to GVHD. Unadjusted odds ratios/coefficients were computed through univariable analysis, followed by adjusted odds ratios (aORs)/coefficients from multivariable analysis that considered potential confounding factors. RESULTS: From 2016 to 2019, data were collected from 13,999 hospitalizations with bone marrow transplants. Among them, 836 had GVHD cases. Patient characteristics showed slight differences in mean age and demographics between the two groups, with GVHD patients having a mean age of 51.61 years and higher percentages of males and whites. Analyzing outcomes, patients with GVHD experienced significantly longer hospital stays (41.4 days vs. 21.3 days) and higher total hospital charges ($824,058 vs. $335,765). Adjusting for confounding factors, GVHD posed a substantial risk. The aOR for mortality in GVHD hospitalizations was 7.20 (95% CI: 5.54-9.36, p < .001). The coefficient for the length of stay was 19.36 days (95% CI: 17.29-21.42, p < .001), and the coefficient for total hospital charges was $453,733 (95% CI: $396,577 to $510,889, p < .001) in GVHD cases. Furthermore, GVHD in patients was associated with elevated risks of various medical conditions. The aORs for sepsis, pneumonia, acute respiratory failure, intubation and mechanical ventilation, Clostridium difficile infection, and acute kidney injury (AKI) in GVHD patients were 2.79 (95% CI: 2.28-3.41, p < .001), 3.30 (95% CI: 2.57-4.24, p < .001), 5.10 (95% CI: 4.01-6.49, p < .001), 4.88 (95% CI: 3.75-6.34, p < .001), 1.45 (95% CI: 1.13-1.86, p = .003), and 3.57 (95% CI: 2.97-4.29, p < .001). CONCLUSION: GVHD in individuals undergoing BMT is linked to elevated mortality rates, prolonged hospitalization, and higher healthcare costs. Moreover, they face a significantly increased risk of developing complications, such as sepsis, pneumonia, acute respiratory failure, C. difficile infection, and AKI. These results underscore the critical need for vigilant monitoring and effective GVHD management to improve patient outcomes and reduce the complications associated with BMT. Nevertheless, further prospective studies are essential to obtain a more profound understanding and a comprehensive assessment of outcomes in these hospitalized patients.

7.
Clin Oral Implants Res ; 35(4): 359-376, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38315151

RESUMO

BACKGROUND: The aim of this systematic review and network meta-analysis (NMA) was to assess the efficacy of different wound-healing agents for palatal donor area management after soft tissue graft harvesting. METHODS: Electronic searches in six databases were conducted for publications up to October 2023. Studies with data from patients undergoing therapeutic approaches using agents for palatal healing after gingival graft harvesting were included. Data about postoperative pain, wound-healing and postoperative complications reported for each agent were extracted. Three different tools were used for the risk of bias within studies evaluation (Murad tool for case series and case report, RoB 2.0 tool for randomized studies and ROBINS-I tool for non-randomized studies). A Bayesian random effects NMA was conducted for postoperative pain levels and wound healing. RESULTS: Eighty-four publications were included in the systematic review (qualitative analysis), with 14 of these subjected to NMA (quantitative analysis). The summarized results from the qualitative and quantitative analysis showed that all wound-healing agents evaluated promoted better pain control and wound healing compared to spontaneous healing and hemostatic sponges alone. The NMA outcomes reveal that leucocyte- and platelet-rich fibrin (L-PRF) was the most effective agent in reducing postoperative pain in all analyzed periods. Moreover, the L-PRF seems to accelerate wound healing and reduce postoperative complications compared to other agents. CONCLUSION: In conclusion, the L-PRF was the most effective agent in reducing postoperative pain, accelerating wound healing and reducing postoperative complications after harvesting soft tissue grafts from the palatal area.


Assuntos
Metanálise em Rede , Dor Pós-Operatória , Palato , Cicatrização , Humanos , Cicatrização/efeitos dos fármacos , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Palato/cirurgia , Fibrina Rica em Plaquetas , Complicações Pós-Operatórias/prevenção & controle , Coleta de Tecidos e Órgãos/métodos , Coleta de Tecidos e Órgãos/efeitos adversos , Gengiva/transplante
8.
Rev Panam Salud Publica ; 48: e24, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38464873

RESUMO

Objective: To obtain a comprehensive overview of organ donation, organ utilization, and discard in the entire donation process in Colombia. Methods: A retrospective study of 1 451 possible donors, distributed in three regions of Colombia, evaluated in 2022. The general characteristics, diagnosis, and causes of contraindication for potential donors were described. Results: Among the 1 451 possible donors, 441 (30.4%) fulfilled brain death criteria, constituting the potential donor pool. Families consented to organ donation in 141 medically suitable cases, while 60 instances utilized legal presumption, leading to 201 eligible donors (13.9%). Of those, 160 (11.0%) were actual donors (in whom operative incision was made with the intent of organ recovery or who had at least one organ recovered). Finally, we identified 147 utilized donors (10.1%) (from whom at least one organ was transplanted). Statistically significant differences were found between age, sex, diagnosis of brain death, and donor critical pathway between regions. A total of 411 organs were transplanted from 147 utilized donors, with kidneys being the most frequently procured and transplanted organs, accounting for 280 (68.1%) of the total. This was followed by 85 livers (20.7%), 31 hearts (7.5%), 14 lungs (3.4%), and 1 pancreas (0.2%). The discard rate of procured deceased donors was 8.1%. Conclusions: About one-tenth of donors are effectively used for transplantation purposes. Our findings highlight areas of success and challenges, providing a basis for future improvements in Colombia.

9.
Emerg Infect Dis ; 29(2): 286-293, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36596569

RESUMO

In March 2022, a 61-year-old woman in France who had received a heart-lung transplant sought treatment with chronic hepatitis mainly characterized by increased liver enzymes. After ruling out common etiologies, we used metagenomic next-generation sequencing to analyze a liver biopsy sample and identified an unknown species of circovirus, tentatively named human circovirus 1 (HCirV-1). We found no other viral or bacterial sequences. HCirV-1 shared 70% amino acid identity with the closest known viral sequences. The viral genome was undetectable in blood samples from 2017-2019, then became detectable at low levels in September 2020 and peaked at very high titers (1010 genome copies/mL) in January 2022. In March 2022, we found >108 genome copies/g or mL in the liver and blood, concomitant with hepatic cytolysis. We detected HCirV-1 transcripts in 2% of hepatocytes, demonstrating viral replication and supporting the role of HCirV-1 in liver damage.


Assuntos
Circovirus , Transplante de Coração-Pulmão , Hepatite A , Hepatite , Feminino , Humanos , Pessoa de Meia-Idade , Circovirus/genética , Genoma Viral
10.
J Evol Biol ; 36(12): 1669-1683, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37822108

RESUMO

The fitness of the host is highly influenced by the interplay between the host and its associated microbiota. The flexible nature of these microbiota enables them to respond swiftly to shifts in the environment, which plays a key role in the host's capacity to withstand environmental stresses. To understand the role of the microbiome in host tolerance to hypoxia, one of the most significant chemical changes occurring in water ecosystems due to climate change, we performed a reciprocal gut transplant experiment with the freshwater crustacean Daphnia magna. In a microbiome transplant experiment, two genotypes of germ-free recipients were inoculated with gut microbiota from Daphnia donors of their own genotype or from the other genotype, that had been either pre-exposed to normoxic or hypoxic conditions. We found that D. magna individuals had a higher survival probability in hypoxia if their microbiome had been pre-exposed to hypoxia. The bacterial communities of the recipients changed over time with a reduction in alpha diversity, which was stronger when donors were pre-exposed to a hypoxic environment. While donor genotype had no influence on the long-term survival probability in hypoxia, donor genotypes was the most influential factor of the microbial community 3 days after the transplantation. Our results indicate that microbiome influencing factors mediate host fitness in a hypoxic environment in a time depending way.


Assuntos
Daphnia magna , Microbiota , Humanos , Animais , Microbiota/genética , Bactérias/genética , Daphnia/genética , Genótipo
11.
J Surg Res ; 284: 303-311, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36628916

RESUMO

INTRODUCTION: Nephrotoxicity is a significant side effect of thoracic transplantation. Many lung transplant patients will require subsequent renal transplantation (KAL). Recently, simultaneous lung/kidney transplants (SLuK) have become an attractive option for patients with end-stage renal disease at the time of lung transplantation. This article explores SLuK outcomes compared to conventional KAL, as well as outcomes among KAL patients against those were KAL listed but never transplanted. MATERIALS AND METHODS: The United Network for Organ Sharing/the Organ Procurement and Transportation Network database was used to identify SLuK patients (n = 74), KAL transplants (n = 456), and patients who were listed for KAL but were never transplanted (n = 626). Significance was determined by chi2, Wilcoxon rank sum test, or independent t-tests. Death-censored graft survival for subgroups was estimated using Kaplan-Meier with log-rank for significance. Analyses were completed using SPSS Statistics 28. RESULTS: The SLuK cohort was older (P = 0.04), more likely diabetic (P < 0.001), and had shorter life expectancies (P < 0.001) than KAL patients. Of those SLuK transplants within 5 y, 84% of patients were alive 1 y post transplant and 82% were alive 3 y post-transplant (compared to 74.6% and 60.3% of overall SLuK). Patients who did undergo KAL were younger and had a lower body mass index (both P < 0.001) compared to those who did not. Those who received a kidney had increased survival times compared to WL patients (P < 0.001). CONCLUSIONS: Conventional KAL transplants are still favorable for average lung recipients. However, recent improvements have made SLuK an option for patients with renal dysfunction. Those patients who were able to receive KAL transplants were better surgical candidates than those who remained on the waitlist.


Assuntos
Falência Renal Crônica , Transplante de Rim , Transplante de Pulmão , Obtenção de Tecidos e Órgãos , Humanos , Transplante de Rim/efeitos adversos , Transplante Homólogo , Falência Renal Crônica/cirurgia , Sobrevivência de Enxerto
12.
Clin Transplant ; 37(4): e14923, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36700660

RESUMO

INTRODUCTION: Dual organ donation and transplantation from living donors (LDs) is a rare practice. Dual organ transplants can be done from the same LD or from different LDs and either simultaneously or sequentially. Simultaneous dual organ transplants from the same LD are of considerable concern due to the magnitude of the donor procedure. METHODS AND RESULTS: According to the UNOS/OPTN and IPTR databases, the US experience of LD dual organ transplants from 1981 to 2021 comprised 101 simultaneous or sequential dual organ transplants from the same LD and 111 transplants from different LDs for a total of 212 LD dual transplants. The first simultaneous or sequential dual organ transplants from either the same LD or different LDs were pancreas-kidney transplants (n = 92). Four additional LD organ transplant combinations have been performed in the United States: liver-kidney (n = 93), lung-kidney (n = 16), liver-intestine (n = 9), and intestine-kidney (n = 2). Only for dual pancreas-kidney (n = 49) and liver-intestinal transplants (n = 4), organs from the same LD have been procured simultaneously. Importantly, no donor deaths have been reported after any simultaneous or sequential procurement. LD dual organ outcomes in all recipient categories have been excellent. CONCLUSIONS: LD dual organ donation and transplantation is safe and successful. Any potential dual organ LD candidate must be subject to the highest level of evaluation scrutiny. A (dual) organ donor registry is warranted for long-term follow-up.


Assuntos
Transplante de Rim , Transplante de Órgãos , Obtenção de Tecidos e Órgãos , Humanos , Estados Unidos , Doadores Vivos , Sobrevivência de Enxerto , Doadores de Tecidos , Sistema de Registros
13.
Clin Transplant ; 37(4): e14893, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36571802

RESUMO

Kidney transplant recipients carrying the CYP3A5*1 allele have lower tacrolimus troughs, and higher dose requirements compared to those with the CYP3A5*3/*3 genotype. However, data on the effect of CYP3A5 alleles on post-transplant tacrolimus management are lacking. The effect of CYP3A5 metabolism phenotypes on the number of tacrolimus dose adjustments and troughs in the first 6 months post-transplant was evaluated in 78 recipients (64% Caucasians). Time to first therapeutic concentration, percentage of time in therapeutic range (TTR), and estimated glomerular filtration rate (eGFR) were also evaluated. Fifty-five kidney transplant recipients were CYP3A5 poor metabolizers (PM), 17 were intermediate metabolizers (IM), and 6 were extensive metabolizers (EM). Compared to PMs, EMs/IMs had significantly more dose adjustments (6.1 vs. 8.1, p = .015). Overall, 33.82% of trough measurements resulted in a dose change. There was no difference in the number of tacrolimus trough measurements between PMs and EM/IMs. The total daily tacrolimus dose requirements were higher in EMs and IMs compared to PMs (<.001). TTR was ∼50% in the PMs and EMs/IMs groups. CYP3A5 EM/IM metabolizers have more tacrolimus dose changes and higher dose requirements which increases clinical management complexity. Larger studies are needed to assess the cost and benefits of including genotyping data to improve clinical management.


Assuntos
Transplante de Rim , Tacrolimo , Humanos , Tacrolimo/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Rim/métodos , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Genótipo , Transplantados , Polimorfismo de Nucleotídeo Único
14.
Ecol Appl ; 33(2): e2779, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36398530

RESUMO

Restoration of degraded areas is now a central tool in humanity's response to continued species-loss. However, restoration projects often report exceedingly slow or failed recolonization of fauna, especially dispersal-constrained groups such as invertebrates. Active interventions via reintroducing or "rewilding" invertebrates may assist recolonization and speed up restoration of communities toward a desired target. However, invertebrate rewilding is rarely implemented during ecological restoration. Here, we studied the efficacy of invertebrate rewilding as a means of reintroducing dispersal-constrained species and improving diversity and compositional similarities to remnant communities during restoration. Rewilding was conducted by transplanting leaf litter and soil, including associated communities of invertebrates from species rich remnant sites into species poor, and geographically isolated, revegetated farmland sites. We sampled pre- and post-rewilding invertebrate communities in remnant, rewilded revegetation, and control revegetation sites. We analyzed morphospecies richness, abundance, community composition, and modeled morphospecies traits (dispersal method/trophic guild) using a Hierarchical Modelling of Species Communities approach to determine which biological properties facilitated establishment. Beetle (Coleoptera) morphospecies richness increased rapidly in rewilded sites and was indistinguishable from remnant communities as early as 7 months post-rewilding. Beetle community similarity in the rewilding sites significantly deviated from the control sites 27 months post-rewilding, however remnant communities remained distinct over the study timeframe. Establishment success varied as other taxa did not respond as consistently as beetles within the study timeframe. Furthermore, there were no discernible shifts in dispersal traits in rewilded sites. However, predatory morphospecies were more likely to establish post-rewilding than other trophic groups. Our results demonstrate that the relatively simple act of transplanting leaf litter can result in comparatively large increases in morphospecies richness during restoration in a short timeframe. We advocate methodologies such as ours should be adopted more frequently to address failed community restoration as they are cost-effective and can be easily applied by practitioners in various restoration settings. However, further efficacy tests (e.g., varying the number of rewilding events) and longer study timeframes are needed to ensure effectiveness for a broader range of invertebrate taxa and ecosystems.


Assuntos
Besouros , Ecossistema , Animais , Invertebrados/fisiologia , Solo , Biodiversidade
15.
Value Health ; 26(2): 204-215, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36243666

RESUMO

OBJECTIVES: This study aimed to estimate the cost-effectiveness of the use of recombinant zoster vaccine (RZV) (Shingrix), which protects against herpes zoster (HZ), among immunocompromised adults aged 19 to 49 years, as a contribution to deliberations of the Advisory Committee on Immunization Practices. METHODS: Hematopoietic cell transplant (HCT) recipients experience a high incidence of HZ, and the efficacy of RZV in preventing HZ has been studied in clinical trials. The cost-effectiveness model calculated incremental cost-effectiveness ratios that compared vaccination with RZV with a no vaccination strategy among adults aged 19 to 49 years. Costs and outcomes were calculated until age 50 years using the healthcare sector perspective and summarized as cost per quality-adjusted life-year (QALY) gained. The base case represents HCT recipients, with scenario analyses representing persons with other immunocompromising conditions, including hematologic malignancies, human immunodeficiency virus, and autoimmune and inflammatory conditions. Uncertainty was investigated using univariate, multivariate, and probabilistic sensitivity analyses. RESULTS: Base-case results indicated vaccination with RZV would avert approximately 35% of HZ episodes and complications, while saving approximately 11% of net costs. Compared with no vaccination, vaccination of HCT recipients with RZV generated cost-savings (ie, lower costs and improved health) in the base case and in 81% of simulations in the probabilistic analysis. In scenario analyses, vaccination cost US dollar ($) 9500/QALY among patients with hematologic malignancies, $79 000/QALY among persons living with human immunodeficiency virus, and $208 000/QALY among persons with selected autoimmune and inflammatory conditions. CONCLUSIONS: Generally favorable economic estimates supported recommendations for vaccination of immunocompromised adults with RZV to prevent episodes of HZ and related complications.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Vacina contra Herpes Zoster , Herpes Zoster , Neuralgia Pós-Herpética , Adulto , Humanos , Análise de Custo-Efetividade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplantados , Neuralgia Pós-Herpética/epidemiologia , Neuralgia Pós-Herpética/prevenção & controle , Análise Custo-Benefício , Herpes Zoster/epidemiologia , Herpes Zoster/prevenção & controle , Vacinas Sintéticas
16.
Transpl Int ; 36: 10800, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36846602

RESUMO

In the last few years, innovative technology and health care digitalization played a major role in all medical fields and a great effort worldwide to manage this large amount of data, in terms of security and digital privacy has been made by different national health systems. Blockchain technology, a peer-to-peer distributed database without centralized authority, initially applied to Bitcoin protocol, soon gained popularity, thanks to its distributed immutable nature in several non-medical fields. Therefore, the aim of the present review (PROSPERO N° CRD42022316661) is to establish a putative future role of blockchain and distribution ledger technology (DLT) in the organ transplantation field and its role to overcome inequalities. Preoperative assessment of the deceased donor, supranational crossover programs with the international waitlist databases, and reduction of black-market donations and counterfeit drugs are some of the possible applications of DLT, thanks to its distributed, efficient, secure, trackable, and immutable nature to reduce inequalities and discrimination.


Assuntos
Blockchain , Humanos , Segurança Computacional , Tecnologia , Atenção à Saúde/métodos
17.
Pediatr Transplant ; 27(7): e14591, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37583096

RESUMO

BACKGROUND: It is unknown how shear wave dispersion (SWD) is displayed in pediatric liver transplant recipients and not fully elucidated how ultrasound shear wave elastography (2D-SWE) display within this cohort, which is important to determine to improve noninvasive surveillance of these patients. The study aimed to compare SWE and SWD values with histopathology in pediatric liver recipients. METHODS: Forty-eight pediatric liver recipients were examined with SWE in conjunction with an elective liver biopsy (clinically without complication). Additionally, SWD values were measured in 21 children. SWE and SWD values were compared to histologically determined fibrosis graded as none-to-mild (F0-1) and moderate-to-severe (F2-4), and inflammation graded as low (grade 0-1) and high (grade 2-4). RESULTS: Two children were excluded due to SWE IQR/median > 30% kPa. The mean age across 46 included patients was 10.9 years (range 1.4-18). The number of patients and median (range) SWE value (kPa) for each stage of fibrosis were: F0-1 [n = 23; 5.8 (3.2-16.1)], F2 [n = 22; 6.0 (4.5-25.9)], F3 [n = 1; 33.3], and F4 [n = 0]. Significantly higher SWE values and greater variability were registered in F2-4 vs. F0-1 (p = .05). Grade of fibrosis correlated weakly to SWE values (r = .3; p = .05), but not to SWD values (r = .2; p = .27). In patients with low-grade inflammation, median SWD was 13.7 m/s KHz (10.7-17.6). Only one patient had high-grade inflammation. CONCLUSIONS: Uncomplicated transplanted liver grafts in a small pediatric cohort revealed slightly increased SWE and SWD values compared to previously reported values in healthy children. This likely reflect both the fibrotic and inflammatory elements in the grafts; however, other confounders impacting the liver's viscoelastic properties are also probable factors.

18.
Pediatr Transplant ; 27(3): e14470, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36651195

RESUMO

BACKGROUND: We used the BSAi (Donor BSA/Recipient BSA) to assess whether transplanting a small or large kidney into a pediatric recipient relative to his/her size influences renal transplant outcomes. METHODS: We included 14 322 single-kidney transplants in pediatric recipients (0-17 years old) (01/2000-02/2020) from the United Network for Organ Sharing database. We divided cases into four BSAi groups (BSAi ≤ 1, 1 < BSAi ≤ 2, 2 < BSAi ≤ 3, BSAi > 3). RESULTS: There were no differences concerning delayed graft function (DGF) or primary non-function (PNF) rates, whether the grafts were from living or brain-dead donors. In both transplants coming from living donors and brain-dead donors, cases with BSAi > 3 and cases with 2 < BSAi ≤ 3 had similar graft survival (p = .13 for transplants from living donors, p = .413 for transplants from brain-dead donors), and both groups had longer graft survival than cases with 1 < BSAi ≤ 2 and cases with BSAi ≤ 1 (p < .001). The difference in 10-year graft survival rates between cases with BSAi > 3 and cases with BSAi ≤ 1 reached around 25% in both donor types. The better graft survival in transplants with BSAi > 2 was confirmed in multivariable analysis. CONCLUSIONS: There is no significant impact of donor-recipient size mismatch on DGF and PNF rates in pediatric renal transplants. However, graft survival is significantly improved when the donor's size is more than twice the pediatric recipient's size.


Assuntos
Nefropatias , Transplante de Rim , Humanos , Criança , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Adolescente , Doadores de Tecidos , Doadores Vivos , Sobrevivência de Enxerto , Taxa de Sobrevida , Morte Encefálica , Sistema de Registros
19.
Oral Dis ; 2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36789456

RESUMO

OBJECTIVE: The aim of this study was to investigate the oral health status among allogeneic transplant recipients who were seen in a multidisciplinary graft-versus-host disease paediatric clinic at the University of California, San Francisco (UCSF). METHODS: This was a retrospective cohort study of patients who underwent allogeneic transplants and were seen in the graft-versus-host disease paediatric clinic between January 2010 and September 2021. Demographic, medical and oral health data were recorded and analysed using descriptive statistics. RESULTS: A total of 25 patients were seen in the paediatric graft-versus-host disease clinic (68% males) with a median age of 12 years at the time of transplant were included. Among them, 12 patients (48%) were diagnosed with oral chronic GVHD, 11 (44%) with dry mouth, four (16%) with oral pseudomembranous candidiasis, one (4%) with recrudescent Herpes Simplex Virus (HSV) infection and one (4%) with mammalian target of rapamycin-inhibitor stomatitis and were managed by the oral medicine team, accordingly with medications, such as topical steroids (44%) and anti-fungal (20%). CONCLUSIONS: HSCT recipients may present with a variety of oral complications. Patients may benefit by a multi-disciplinary approach including a dental specialist as part of the cancer care team.

20.
Acta Paediatr ; 112(3): 557-568, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36567640

RESUMO

AIM: Our aim was to evaluate cardiovascular risk profile in 42 children with kidney transplants (KT) at the Queen Silvia Children's Hospital, Gothenburg Sweden. METHODS: Forty-two children (7.1-18 years) with KT, time from transplantation 3.5 (0.9-13) years, were examined at inclusion and annually for three consecutive years. Eighteen matched controls were examined once. Cardiovascular phenotyping included ultra-high-frequency ultrasound (UHFUS), pulse wave velocity (PWV), and endothelial function. RESULTS: Children with KT had higher body mass index (BMI) z-score and blood pressure (BP) z-score than healthy controls (BMI z-score: 0.4 ± 1.0 and - 0.2 ± 0.9, respectively, p = 0.02; SBP z-score: 0.5 ± 0.9 and - 0.8 ± 0.7; DBP z-score: 0.7 ± 0.7 and - 0.3 ± 0.5, respectively, p < 0.001). BP z-score decreased significantly over 3 years; other vascular markers remained unchanged. PWV and carotid intima thickness (IT) were higher in children with KT compared to healthy controls. Children with pre-emptive KT had lower radial IT and dorsal pedal media thickness (MT) compared to children with preceding dialysis. CONCLUSION: Children with KT show increased cardiovascular risk parameters, not increasing over time. Children on dialysis before KT have more pronounced vascular changes than those with pre-emptive KT, suggesting pre-emptive transplantation more beneficial for cardiovascular health.


Assuntos
Transplante de Rim , Rigidez Vascular , Humanos , Criança , Seguimentos , Análise de Onda de Pulso , Pressão Sanguínea/fisiologia , Diálise Renal , Espessura Intima-Media Carotídea , Rigidez Vascular/fisiologia
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