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1.
Transplantation ; 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38383958

RESUMO

Delayed graft function (DGF) is an early posttransplant complication predictive of adverse outcomes. This "acute kidney injury of transplantation" is often defined as allograft dysfunction requiring renal replacement within 7 d posttransplantation. DGF is an important area of study because it is emerging with efforts to expand the donor pool and address the supply-demand gap in kidney transplantation. DGF is often caused by severe kidney injury mechanisms because of multiple donors, recipients, and immunologic factors. The role of kidney biopsy, particularly in prolonged DGF, is an ongoing area of research and inquiry for clinicians and researchers alike to better define, manage, and predict outcomes of this early posttransplant event. This review aims to provide an in-depth, comprehensive summary of the literature to date on the histopathology of DGF and the role of kidney transplant biopsies in prolonged DGF.

2.
Ann Chir Plast Esthet ; 69(1): 53-58, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36737354

RESUMO

BACKGROUND: Pectus excavatum (PE) is the most common congenital chest wall deformity, whose cardiopulmonary consequences are controversial. PE surgery is in our experience usually performed for aesthetic reasons. OBJECTIVES: The aim of this study was to evaluate the impact of PE on respiratory function and exercise capacity in patients with PE before patient-specific silicone implant correction. METHODS: This monocentric prospective study conducted at Toulouse University Hospital included sixty patients scheduled for custom-made silicone implants correction. Respiratory function (pulmonary function tests (FPTs)) and exercise capacity (VO2 max) were measured before surgery. RESULTS: Before surgery, no (0/60) restrictive lung disease was detected, with a mean total lung capacity (TLC) of 98.5% of predicted value (IC 95%; 80.4-137). Median VO2 max (n=56) was normal (89% predicted), with no cardiac limitation. CONCLUSION: In this cohort, PE had no impact on respiratory function nor exercise capacity. In patients without cardiac or respiratory effects of PE, silicone implants should be considered the preferred approach as it adequately addressed patients' main complaint of low self-esteem.


Assuntos
Tórax em Funil , Humanos , Tórax em Funil/cirurgia , Silicones , Tolerância ao Exercício , Estudos Prospectivos , Próteses e Implantes
3.
Clin Transplant ; 38(1): e15217, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38078682

RESUMO

BACKGROUND: While presumably less common with modern molecular diagnostic and imaging techniques, fever of unknown origin (FUO) remains a challenge in kidney transplant recipients (KTRs). Additionally, the impact of FUO on patient and graft survival is poorly described. METHODS: A cohort of adult KTRs between January 1, 1995 and December 31, 2018 was followed at the University of Wisconsin Hospital. Patients transplanted from January 1, 1995 to December 31, 2005 were included in the "early era"; patients transplanted from January 1, 2006 to December 31, 2018 were included in the "modern era". The primary objective was to describe the epidemiology and etiology of FUO diagnoses over time. Secondary outcomes included rejection, graft and patient survival. RESULTS: There were 5590 kidney transplants at our center during the study window. FUO was identified in 323 patients with an overall incidence rate of .8/100 person-years. Considering only the first 3 years after transplant, the incidence of FUO was significantly lower in the modern era than in the early era, with an Incidence Rate Ratio (IRR) per 100 person-years of .48; 95% CI: .35-.63; p < .001. A total of 102 (31.9%) of 323 patients had an etiology determined within 90 days after FUO diagnosis: 100 were infectious, and two were malignancies. In the modern era, FUO remained significantly associated with rejection (HR = 44.1; 95% CI: 16.6-102; p < .001) but not graft failure (HR = 1.21; 95% CI: .68-2.18; p = .52) total graft loss (HR = 1.17; 95% CI: .85-1.62; p = .34), or death (HR = 1.17; 95% CI: .79-1.76; p = .43. CONCLUSIONS: FUO is less common in KTRs during the modern era. Our study suggests infection remains the most common etiology. FUO remains associated with significant increases in risk of rejection, warranting further inquiry into the management of immunosuppressive medications in SOT recipients in the setting of FUO.


Assuntos
Febre de Causa Desconhecida , Transplante de Rim , Neoplasias , Adulto , Humanos , Incidência , Transplante de Rim/efeitos adversos , Febre de Causa Desconhecida/epidemiologia , Febre de Causa Desconhecida/etiologia , Febre de Causa Desconhecida/diagnóstico
4.
Phys Rev Lett ; 131(8): 083002, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37683165

RESUMO

We report on an evaluation of an optical clock that uses the ^{2}S_{1/2}→^{2}D_{5/2} transition of a single ^{88}Sr^{+} ion as the reference. In contrast to previous work, we estimate the effective temperature of the blackbody radiation that shifts the reference transition directly during operation from the corresponding frequency shift and the well-characterized sensitivity to thermal radiation. We measure the clock output frequency against an independent ^{171}Yb^{+} ion clock, based on the ^{2}S_{1/2}(F=0)→^{2}F_{7/2}(F=3) electric octupole (E3) transition, and determine the frequency ratio with a total fractional uncertainty of 2.3×10^{-17}. Relying on a previous measurement of the ^{171}Yb^{+} (E3) clock frequency, we find the absolute frequency of the ^{88}Sr^{+} clock transition to be 444 779 044 095 485.277(59) Hz. Our result reduces the uncertainty by a factor of 3 compared with the previously most accurate measurement and may help to resolve so far inconsistent determinations of this value. We also show that for three simultaneously interrogated ^{88}Sr^{+} ions, the increased number causes the expected improvement of the short-term frequency instability of the optical clock without degrading its systematic uncertainty.

5.
J Toxicol Environ Health B Crit Rev ; 25(7): 372-392, 2022 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-36253946

RESUMO

The objectives of this systematic review of original articles published up until August 2021 and meta-analyses were to identify the links between occupational and non-occupational environmental exposures, types of occupations and idiopathic pulmonary fibrosis (IPF). Sixteen selected case-control studies were qualified as good level with Newcastle-Ottawa quality assessment scale. Sensitivity analyses highlighted the role of choice of control group, tobacco adjustment and diagnostic tools. Significantly increased risks of IPF were observed (OR (95%CI): for metals (1.42(1.05-1.92)), wood (OR:1.32(1.02-1.71)), and general dust (OR:1.32(1.08-1.63)) exposures. Subgroup analyses found a significantly elevated risk for: hardwood (OR:1.75 (1.13-2.70)), organic dusts (OR:1.72 (1.20-2.46)) and pesticides (OR:2.30 (1.30-4.08)), while no significant change was noted for softwoods and solvents. Smoking adjustments: general dust (1.45 (1.04-2.03)/organic dust (2.5 (1.49-4.22)/metals (1.87 (1.16-3)/wood dust OR: 1.16 (0.86-1.61)/pesticide exposure 2.4 (0.84-6.9) were calculated. Among agricultural workers, the risk was also increased (OR:2.06 (1.02-4.16)). Few environmental data were available and no significant associations detected. Thus, these meta-analyses highlighted the role of some occupational exposures in IPF occurrence. A more accurate and thorough assessment of exposures over the entire working life as well as on the duration and intensity of exposure and complex of multi-pollutant exposure is needed in future research and clinical practice.


Assuntos
Poluentes Ambientais , Fibrose Pulmonar Idiopática , Exposição Ocupacional , Praguicidas , Humanos , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/epidemiologia , Poeira , Exposição Ocupacional/efeitos adversos , Metais , Solventes
6.
Eur J Immunol ; 52(11): 1819-1828, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36189878

RESUMO

Anti-viral T-cell responses are usually directed against a limited set of antigens, but often contain many T cells expressing different T-cell receptors (TCRs). Identical TCRs found within virus-specific T-cell populations in different individuals are known as public TCRs, but also TCRs highly-similar to these public TCRs, with only minor variations in amino acids on specific positions in the Complementary Determining Regions (CDRs), are frequently found. However, the degree of freedom at these positions was not clear. In this study, we used the HLA-A*02:01-restricted EBV-LMP2FLY -specific public TCR as model and modified the highly-variable position 5 of the CDR3ß sequence with all 20 amino acids. Our results demonstrate that amino acids at this particular position in the CDR3ß region of this TCR are completely inter-changeable, without loss of TCR function. We show that the inability to find certain variants in individuals is explained by their lower recombination probability rather than by steric hindrance.


Assuntos
Aminoácidos , Receptores de Antígenos de Linfócitos T , Linfócitos T , Peptídeos/metabolismo , Receptores de Antígenos de Linfócitos T alfa-beta
7.
Front Immunol ; 13: 851868, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401538

RESUMO

Since multiple different T-cell receptor (TCR) sequences can bind to the same peptide-MHC combination and the number of TCR-sequences that can theoretically be generated even exceeds the number of T cells in a human body, the likelihood that many public identical (PUB-I) TCR-sequences frequently contribute to immune responses has been estimated to be low. Here, we quantitatively analyzed the TCR-repertoires of 190 purified virus-specific memory T-cell populations, directed against 21 epitopes of Cytomegalovirus, Epstein-Barr virus and Adenovirus isolated from 29 healthy individuals, and determined the magnitude, defined as prevalence within the population and frequencies within individuals, of PUB-I TCR and of TCR-sequences that are highly-similar (PUB-HS) to these PUB-I TCR-sequences. We found that almost one third of all TCR nucleotide-sequences represented PUB-I TCR amino-acid (AA) sequences and found an additional 12% of PUB-HS TCRs differing by maximally 3 AAs. We illustrate that these PUB-I and PUB-HS TCRs were structurally related and contained shared core-sequences in their TCR-sequences. We found a prevalence of PUB-I and PUB-HS TCRs of up to 50% among individuals and showed frequencies of virus-specific PUB-I and PUB-HS TCRs making up more than 10% of each virus-specific T-cell population. These findings were confirmed by using an independent TCR-database of virus-specific TCRs. We therefore conclude that the magnitude of the contribution of PUB-I and PUB-HS TCRs to these virus-specific T-cell responses is high. Because the T cells from these virus-specific memory TCR-repertoires were the result of successful control of the virus in these healthy individuals, these PUB-HS TCRs and PUB-I TCRs may be attractive candidates for immunotherapy in immunocompromised patients that lack virus-specific T cells to control viral reactivation.


Assuntos
Infecções por Vírus Epstein-Barr , Citomegalovirus , Herpesvirus Humano 4 , Humanos , Receptores de Antígenos de Linfócitos T , Linfócitos T
8.
Am J Transplant ; 22(1): 266-273, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34467618

RESUMO

Increasing numbers of compatible pairs are choosing to enter paired exchange programs, but motivations, outcomes, and system-level effects of participation are not well described. Using a linkage of the Scientific Registry of Transplant Recipients and National Kidney Registry, we compared outcomes of traditional (originally incompatible) recipients to originally compatible recipients using the Kaplan-Meier method. We identified 154 compatible pairs. Most pairs sought to improve HLA matching. Compared to the original donor, actual donors were younger (39 vs. 50 years, p < .001), less often female (52% vs. 68%, p < .01), higher BMI (27 vs. 25 kg/m², p = .03), less frequently blood type O (36% vs. 80%, p < .001), and had higher eGFR (99 vs. 94 ml/min/1.73 m², p = .02), with a better LKDPI (median 7 vs. 22, p < .001). We observed no differences in graft failure or mortality. Compatible pairs made 280 additional transplants possible, many in highly sensitized recipients with long wait times. Compatible pair recipients derived several benefits from paired exchange, including better donor quality. Living donor pairs should receive counseling regarding all options available, including kidney paired donation. As more compatible pairs choose to enter exchange programs, consideration should be given to optimizing compatible pair and hard-to-transplant recipient outcomes.


Assuntos
Transplante de Rim , Obtenção de Tecidos e Órgãos , Seleção do Doador , Feminino , Humanos , Doadores Vivos , Motivação , Transplantados
9.
Transpl Infect Dis ; 24(1): e13768, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34825437

RESUMO

INTRODUCTION: BK polyomavirus (BKV) is a common infection among kidney transplant recipients (KTR). Risk factors and outcomes based on donor characteristics remain largely unknown. METHODS: In this study, we aimed to analyze the impact of donor factors through a paired kidney analysis. We included 289 pairs of adult deceased donor transplants (578 KTRs total); each pair had received kidneys from the same donor. Recipient pairs were divided into three groups: "no BK group" if neither KTR developed BK viremia (n = 336), "discordant" if the only one did (n = 176), and "concordant" if both did (n = 66). Acute rejection (AR), graft failure, and BK nephropathy (BKN) were outcomes of interest. RESULTS: Donors in the concordant group were younger, had lower kidney donor profile index (KDPI), and were less likely to be donor after circulatory death (DCD). In multivariate analyses, KTRs who had a donor with a higher body mass index (BMI) (hazard ratio (HR): 0.97; 95% confidence interval (CI): 0.95-0.99; p = .009) were less likely to develop BKV. Concordance was not associated with AR (HR: 0.83; 95% CI: 0.51-1.34; p = .45), graft failure (HR: 1.77; 95% CI: 0.42-7.50; p = .43), or BKN (HR: 1.02; 95% CI: 0.51-2.03; p = .96). DISCUSSION: Our study suggests lower donor BMI is associated with BKV infection, and concordance or discordance between paired kidney recipients is not associated with poor outcomes.


Assuntos
Vírus BK , Transplante de Rim , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Adulto , Humanos , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/epidemiologia , Fatores de Risco , Transplantados , Infecções Tumorais por Vírus/epidemiologia , Viremia/epidemiologia
10.
Int J Mol Sci ; 22(22)2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34830090

RESUMO

Recent studies have identified sex-differences in auditory physiology and in the susceptibility to noise-induced hearing loss (NIHL). We hypothesize that 17ß-estradiol (E2), a known modulator of auditory physiology, may underpin sex-differences in the response to noise trauma. Here, we gonadectomized B6CBAF1/J mice and used a combination of electrophysiological and histological techniques to study the effects of estrogen replacement on peripheral auditory physiology in the absence of noise exposure and on protection from NIHL. Functional analysis of auditory physiology in gonadectomized female mice revealed that E2-treatment modulated the peripheral response to sound in the absence of changes to the endocochlear potential compared to vehicle-treatment. E2-replacement in gonadectomized female mice protected against hearing loss following permanent threshold shift (PTS)- and temporary threshold shift (TTS)-inducing noise exposures. Histological analysis of the cochlear tissue revealed that E2-replacement mitigated outer hair cell loss and cochlear synaptopathy following noise exposure compared to vehicle-treatment. Lastly, using fluorescent in situ hybridization, we demonstrate co-localization of estrogen receptor-2 with type-1C, high threshold spiral ganglion neurons, suggesting that the observed protection from cochlear synaptopathy may occur through E2-mediated preservation of these neurons. Taken together, these data indicate the estrogen signaling pathways may be harnessed for the prevention and treatment of NIHL.


Assuntos
Cóclea , Estradiol/farmacologia , Potenciais Evocados Auditivos/efeitos dos fármacos , Perda Auditiva Provocada por Ruído , Animais , Cóclea/metabolismo , Cóclea/patologia , Cóclea/fisiopatologia , Feminino , Perda Auditiva Provocada por Ruído/metabolismo , Perda Auditiva Provocada por Ruído/patologia , Perda Auditiva Provocada por Ruído/fisiopatologia , Perda Auditiva Provocada por Ruído/prevenção & controle , Camundongos , Ovariectomia
11.
Rev Mal Respir ; 38(10): 972-979, 2021 Dec.
Artigo em Francês | MEDLINE | ID: mdl-34629221

RESUMO

EPIDemio study is a multicenter, prospective and observational study. The objective is to estimate the prevalence and incidence of fibrosing interstitial lung diseases (ILDs) in the department of Haute Garonne (31) in France. Fifty-five pulmonologists from the Toulouse university hospital and 8 private establishments participated in this study. Two hundred and fifty-six cases of fibrosing ILDs were reported (gross overall prevalence: 22.8/100,000 and estimated 30.1/100,000. Idiopathic ILDs represent 55.8% of fibrosing ILDs ahead of systemic disease-related ILDs (24.6%) and ILDs associated with environmental exposure (13.3%). Idiopathic pulmonary fibrosis (IPF) represents 35.9% of fibrosing ILDs, which corresponds to a minimal prevalence of 8.2/100,000 and an estimated prevalence of 11.2/100,000. This study confirms epidemiological data collected in France and Europe.


Assuntos
Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Progressão da Doença , Fibrose , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/epidemiologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/epidemiologia , Estudos Prospectivos
12.
Int J Radiat Biol ; 97(9): 1217-1228, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34232830

RESUMO

RATIONALE: The role of radiation-induced bystander effects in cancer therapy with alpha-particle emitting radiopharmaceuticals remains unclear. With renewed interest in using alpha-particle emitters to sterilize disseminated tumor cells, micrometastases, and tumors, a better understanding of the direct effects of alpha particles and the contribution of the bystander responses they induce is needed to refine dosimetric models that help predict clinical benefit. Accordingly, this work models and quantifies the relative importance of direct effects (DE) and bystander effects (BE) in the growth delay of human breast cancer xenografts observed previously in the tibiae of mice treated with 223RaCl2. METHODS: A computational model of MDA-MB-231 and MCF-7 human breast cancer xenografts in the tibial bone marrow of mice administered 223RaCl2 was created. A Monte Carlo radiation transport simulation was performed to assess individual cell absorbed doses. The responses of the breast cancer cells to direct alpha particle irradiation and gamma irradiation were needed as input data for the model and were determined experimentally using a colony-forming assay and compared to the responses of preosteoblast MC3T3-E1 and osteocyte-like MLO-Y4 bone cells. Using these data, a scheme was devised to simulate the dynamic proliferation of the tumors in vivo, including DE and BE propagated from the irradiated cells. The parameters of the scheme were estimated semi-empirically to fit experimental tumor growth. RESULTS: A robust BE component, in addition to a much smaller DE component, was required to simulate the in vivo tumor proliferation. We also found that the relative biological effectiveness (RBE) for cell killing by alpha particle radiation was greater for the bone cells than the tumor cells. CONCLUSION: This modeling study demonstrates that DE of radiation alone cannot explain experimental observations of 223RaCl2-induced growth delay of human breast cancer xenografts. Furthermore, while the mechanisms underlying BE remain unclear, the addition of a BE component to the model is necessary to provide an accurate prediction of the growth delay. More complex models are needed to further comprehend the extent and complexity of 223RaCl2-induced BE.


Assuntos
Medula Óssea/efeitos da radiação , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Transformação Celular Neoplásica , Modelos Biológicos , Rádio (Elemento)/uso terapêutico , Partículas alfa/uso terapêutico , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos da radiação , Feminino , Camundongos , Método de Monte Carlo , Eficiência Biológica Relativa
13.
Kidney Int Rep ; 6(6): 1642-1652, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34169205

RESUMO

INTRODUCTION: It is critical to identify kidney transplant recipients (KTRs) at higher risk for adverse outcomes, to focus on monitoring and interventions to improve outcomes. We examined the associations between graft function variability and long-term outcomes in KTRs in an observational study. METHODS: We identified 2919 KTRs in the Wisconsin Allograft Recipient Database (WisARD) who had a functioning allograft 2 years posttransplantation and at least 3 outpatient measurements of estimated glomerular filtration rate (eGFR) from 1 to 2 years posttransplantation. Graft function slope was calculated from a linear regression of eGFR, and variability was defined as the coefficient of variation around this regression line. Associations of eGFR variability and slope with death, graft failure, cardiovascular events, and acute rejection were estimated. RESULTS: Compared to the lowest quartile, the highest quartile of eGFR variability was associated with a higher risk of death (adjusted hazard ratio [HR] = 1.85; 95% CI = 1.23-2.76), but not with a higher risk of graft failure (subhazard ratio = 1.16; 95% CI = 0.85-1.58), independent of eGFR and slope of eGFR. Greater eGFR variability was associated with higher risk of cardiovascular- and infection-related death and cardiovascular events but not malignancy-related death or allograft rejection. Including variability of eGFR significantly improved prediction of mortality but not prediction of graft failure. CONCLUSION: Variability of eGFR is independently associated with risk of death, especially cardiovascular disease-related death and cardiovascular events, but not graft failure. Variability of eGFR may help identify KTRs at higher risk for death and cardiovascular events.

14.
Am J Kidney Dis ; 78(3): 418-428, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33992729

RESUMO

Optimal glycemic control in kidney transplant recipients with diabetes is associated with improved morbidity and better patient and allograft survival. Transplant options for patients with diabetes requiring insulin therapy and chronic kidney disease who are suitable candidates for kidney transplantation should include consideration of ß-cell replacement therapy: pancreas or islet transplantation. International variation related to national regulatory policies exists in offering one or both options to suitable candidates and is further affected by pancreas/islet allocation policies and transplant waiting list dynamics. The selection of appropriate candidates depends on patient age, coexistent morbidities, the timing of referral to the transplant center (predialysis versus on dialysis) and availability of living kidney donors. Therefore, early referral (estimated glomerular filtration rate < 30 mL/min/1.73 m2) is of the utmost importance to ensure adequate time for informed decision making and thorough pretransplant evaluation. Obesity, cardiovascular disease, peripheral vascular disease, smoking, and frailty are some of the conditions that need to be addressed before acceptance on the transplant list, and ideally before dialysis becoming imminent. This review offers insights into selection of pancreas/islet transplant candidates by transplant centers and an update on posttransplant outcomes, which may have practice implications for referring nephrologists.


Assuntos
Diabetes Mellitus Tipo 1/complicações , Nefropatias/cirurgia , Transplante de Rim/métodos , Doadores Vivos , Complicações Pós-Operatórias/epidemiologia , Saúde Global , Sobrevivência de Enxerto , Humanos , Morbidade/tendências , Transplante Homólogo
15.
Front Immunol ; 12: 630440, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33854504

RESUMO

T-cell products derived from third-party donors are clinically applied, but harbor the risk of off-target toxicity via induction of allo-HLA cross-reactivity directed against mismatched alleles. We used third-party donor-derived virus-specific T cells as model to investigate whether virus-specificity, HLA restriction and/or HLA background can predict the risk of allo-HLA cross-reactivity. Virus-specific CD8pos T cells were isolated from HLA-A*01:01/B*08:01 or HLA-A*02:01/B*07:02 positive donors. Allo-HLA cross-reactivity was tested using an EBV-LCL panel covering 116 allogeneic HLA molecules and confirmed using K562 cells retrovirally transduced with single HLA-class-I alleles of interest. HLA-B*08:01-restricted T cells showed the highest frequency and diversity of allo-HLA cross-reactivity, regardless of virus-specificity, which was skewed toward multiple recurrent allogeneic HLA-B molecules. Thymic selection for other HLA-B alleles significantly influenced the level of allo-HLA cross-reactivity mediated by HLA-B*08:01-restricted T cells. These results suggest that the degree and specificity of allo-HLA cross-reactivity by T cells follow rules. The risk of off-target toxicity after infusion of incompletely matched third-party donor-derived virus-specific T cells may be reduced by selection of T cells with a specific HLA restriction and background.


Assuntos
Antígenos HLA/imunologia , Linfócitos T/imunologia , Vírus/imunologia , Alelos , Reações Cruzadas , Citomegalovirus/imunologia , Antígenos HLA/genética , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 4/imunologia , Teste de Histocompatibilidade , Humanos , Imunoterapia Adotiva , Células K562 , Doadores de Tecidos
16.
Transplant Proc ; 53(5): 1462-1469, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33579551

RESUMO

Delayed graft function (DGF) after kidney transplantation is associated with an increased risk of graft failure. We studied the histologic findings among adult kidney transplant recipients transplanted between January 2000 and June 2015 who had DGF and had a kidney biopsy within 14 days of transplant. Death censored graft failure (DCGF) and death at 1 and 3 years after transplant were examined. A total of 269 transplant recipients fulfilled our selection criteria, of which 152 (56.51%) had acute tubular necrosis (ATN), 44 (16.4%) had acute rejection (AR), mainly T-cell mediated rejection (n = 31), 35 (13%) had ATN with AR (mainly T-cell mediated rejection, n = 26), and 38 (14.1%) had other pathology. Compared with those with ATN alone, kidney transplant recipients with AR alone had a significantly higher risk of DCGF at 1 year post transplant (adjusted hazard ratio = 3.70; 95% confidence interval 1.5-9.5; P = .006). Those with AR alone had an increased risk of DCGF at 3 years post transplant (hazard ratio = 3.10; 95% confidence interval 1.3-8.5; P = .01) in crude analyses. There was no association between DGF etiology and mortality. Early renal biopsy can be used to distinguish AR, which has protocolized treatments, from other etiologies. This could potentially alter allograft survival within 1 year of transplant complicated by DGF.


Assuntos
Biópsia/estatística & dados numéricos , Função Retardada do Enxerto/mortalidade , Rejeição de Enxerto/mortalidade , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/mortalidade , Adulto , Função Retardada do Enxerto/etiologia , Função Retardada do Enxerto/patologia , Feminino , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Humanos , Incidência , Rim/patologia , Necrose Tubular Aguda/etiologia , Necrose Tubular Aguda/mortalidade , Necrose Tubular Aguda/patologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Transplantes/patologia
17.
Transpl Infect Dis ; 23(3): e13561, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33400361

RESUMO

BACKGROUNDS: Effective management of BK viremia (BKPyV-DNAemia) in kidney transplant recipients (KTRs) involves regular monitoring and adjustment of immunosuppression. With this strategy, the majority of patients will clear BK or have ongoing, but non-significant, low-level BKPyV-DNAemia. However, despite adjustments, some will develop more severe sequelae of BK including BKPyV-DNAemia >5 log10 copies/mL and BK nephropathy, and others may develop de novo DSA (dnDSA) or acute rejection (AR). METHODS: This was a single-center study of KTRs transplanted at the University of Wisconsin-Madison between 01/01/2015 and 12/31/2017. In this study, we sought to elucidate characteristics associated with the progression of BKPyV-DNAemia to unfavorable outcomes after decreasing immunosuppressive medications for the management of BK viremia as described in consensus guidelines. RESULTS: A total of 224 KTRs fulfilled our selection criteria; 118 (53%) resolved or had persistent low DNAemia, 64 (28%) had severe BK/nephropathy, and 42 (19%) developed dnDSA or AR. In multivariable analysis, female gender (HR: 2.05; 95% CI: 1.08-3.90; P = .02); previous rejection (HR: 2.90; 95% CI: 1.04-8.12; P = .04), and early infection (HR: 0.81; 95% CI: 0.72-0.90; P < .001) were associated with the development of severe BK/nephropathy. Conversely, non-depleting induction at transplant (HR: 2.06; 95% CI: 1.03-4.11; P = .03), HLA mismatches >3 (HR: 2.27; HR: 1.01-5.06; P = .04), and delayed graft function (HR: 4.14; 95% CI: 1.12-15.28; P = .03) were associated with development of dnDSA and/or rejection. CONCLUSION: Our study suggests that almost half of KTRs with BKPyV-DNAemia managed by our immunosuppressant adjustment protocol progress unfavorably. Identification of these risk factors could assist the frontline clinician in creating an individualized immunosuppressive modification plan potentially mitigating negative outcomes.


Assuntos
Vírus BK , Transplante de Rim , Infecções por Polyomavirus , Feminino , Humanos , Imunossupressores , Fatores de Risco , Infecções Tumorais por Vírus
18.
Kidney Int Rep ; 5(12): 2228-2237, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33305116

RESUMO

INTRODUCTION: Opportunistic viral infections cause extensive morbidity and mortality in kidney transplant recipients (KTRs). Low serum albumin levels before and after transplant have been associated with negative outcomes. However, it is uncertain whether serum albumin levels before transplantation are associated with the risk for post-transplantation opportunistic BK polyomavirus (BKV) or cytomegalovirus (CMV). METHODS: We reviewed all KTRs transplanted at our institution between 1 January 2005 and 31 December 2015 with serum albumin measured within 45 days before transplantation in a retrospective observational cohort study. Selected patients were stratified into 3 groups: normal albuminemia (≥3.5 g/dl), moderate hypoalbuminemia (3.49-2.5 g/dl), and severe hypoalbuminemia (<2.5 g/dl). Patients were observed for post-transplantation BKV or CMV according to standard of care. RESULTS: We included 1717 patients in this study; 72.3% had normal serum albumin, 26.3% had moderate hypoalbuminemia, and 1.5% had severe hypoalbuminemia. Moderate and severe hypoalbuminemia incurred a higher risk for BKV compared with normal serum albumin levels in univariable analysis (moderate hypoalbuminemia: hazard ratio [HR] = 1.5; 95% confidence interval [CI], 1.14-1.90; P = .003); severe hypoalbuminemia: HR = 2.15; 95% CI, 1.01-4.56; P = 0.05). Although not significant after multivariable adjustment, there was still 18% increased risk in moderate hypoalbuminemia and 64% in severe hypoalbuminemia for BKV compared with the normal albumin group. Moderate hypoalbuminemia was associated with a higher risk for CMV infection than normal serum albumin levels in multivariable analysis, although it was not statistically significant (HR = 1.15; 95% CI, 0.36-3.64; P = 0.81). CONCLUSIONS: These findings suggest that pretransplantation hypoalbuminemia is associated with a higher risk for post-transplantation BKV and possibly CMV. More intense screening is warranted for these viruses in recipients with pretransplant hypoalbuminemia.

19.
Rev. cuba. anestesiol. reanim ; 19(3): e631, sept.-dic. 2020. tab
Artigo em Espanhol | CUMED, LILACS | ID: biblio-1138884

RESUMO

Introducción: El aumento de la expectativa de vida determina un incremento en la incidencia de enfermedades con indicación quirúrgica. El avance en las técnicas quirúrgicas, los cuidados intensivos y el conocimiento más profundo del proceso de envejecimiento tiende a favorecer la disminución de la morbimortalidad perioperatoria del paciente geriátrico. Objetivo: Determinar la incidencia de complicaciones intra y posoperatorias en pacientes geriátricos durante la cirugía abdominal mayor electiva. Métodos: Se realizó un estudio observacional descriptivo, de corte transversal a 373 pacientes geriátricos programados para intervención quirúrgica abdominal mayor desde enero de 2017 hasta diciembre de 2019 en el Hospital Clínico Quirúrgico Dr. Miguel Enríquez. Se registró la incidencia de complicaciones perioperatorias relacionándolas con las variables de estudio. Resultados: Las complicaciones más frecuentes fueron las cardiovasculares. La mortalidad fue escasa. Conclusiones: Las complicaciones perioperatorias detectadas en los pacientes geriátricos estudiados, se relacionan con las enfermedades previas, el tipo y la envergadura de la cirugía y con el tiempo quirúrgico(AU)


Introduction: The increase in life expectancy determines an increase in the incidence of diseases with surgical indication. Advances in surgical techniques, intensive care and deeper understanding of the aging process tend to favor the reduction of perioperative morbidity and mortality among geriatric patients. Objective: To determine the incidence of intraoperative and postoperative complications among geriatric patients during elective major abdominal surgery. Methods: A descriptive, cross-sectional and observational study was carried out with 373 geriatric patients scheduled for major abdominal surgery from January 2017 to December 2019 at Dr. Miguel Enríquez Clinical-Surgical Hospital. The incidence of perioperative complications was recorded, relating them to the study variables. Results: The most frequent complications were the cardiovascular ones. Mortality was low. Conclusions: The perioperative complications identified among the geriatric patients studied are related with previous diseases, with the type and extent of surgery, and with the surgical time(AU)


Assuntos
Humanos , Idoso , Idoso de 80 Anos ou mais , Complicações Pós-Operatórias/prevenção & controle , Indicadores de Morbimortalidade , Assistência Perioperatória/métodos , Abdome/cirurgia , Cuidados Intraoperatórios/métodos , Complicações Pós-Operatórias/epidemiologia , Envelhecimento , Epidemiologia Descritiva , Estudos Transversais , Estudo Observacional
20.
Kidney Int Rep ; 5(11): 1894-1905, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32864513

RESUMO

INTRODUCTION: The scope of the impact of the coronavirus disease 2019 (COVID-19) pandemic on living donor kidney transplantation (LDKT) practices is not well defined. METHODS: We surveyed US transplant programs to assess practices, strategies, and barriers to living LDKT during the COVID-19 pandemic. After institutional review board approval, the survey was distributed from 9 May 2020 to 30 May 2020 by e-mail and postings to professional society list-servs. Responses were stratified based on state COVID-19 cumulative incidence levels. RESULTS: Staff at 118 unique centers responded, representing 61% of US living donor recovery programs and 75% of LKDT volume in the prepandemic year. Overall, 66% reported that LDKT surgery was on hold (81% in "high" vs. 49% in "low" COVID-19 cumulative incidence states). A total of 36% reported that evaluation of new donor candidates had paused, 27% reported that evaluations were very much decreased (>0% to <25% typical), and 23% reported that evaluations were moderately decreased (25% to <50% typical). Barriers to LDKT surgery included program concerns for donor (85%) and recipient (75%) safety, patient concerns (56%), elective case restrictions (47%), and hospital administrative restrictions (48%). Programs with higher local COVID-19 cumulative incidence reported more barriers related to staff and resource diversion. Most centers continuing donor evaluations used remote strategies (video, 82%; telephone, 43%). As LDKT resumes, all programs will screen for COVID-19, although timeframe and modalities will vary. Recommendations for presurgical self-quarantine are also variable. CONCLUSION: The COVID-19 pandemic has had broad impacts on LDKT practice. Ongoing research and consensus building are needed to reduce barriers, to guide optimal practices, and to support safe restoration of LDKT across centers.

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