Contribution of Estimates of Glomerular Filtration to the Extensive Disparities in Preemptive Listing for Kidney Transplant.

Introduction: The use of race coefficients in equations for estimated glomerular filtration rate (eGFR) may have contributed to racial disparities in access to preemptive (without dialysis exposure) kidney transplantation (Ktx). Methods: In this retrospective national cohort study of incident kidney transplant candidates in the United States from 2001 to 2019, we describe temporal trends and racial disparities in preemptive listing and the distribution of eGFR at listing, using eGFR as reported and after removing the race coefficient for Black candidates. Results: Among 511,686 candidates, preemptive listing increased over time, from 18% in 2001 to 33% in 2019. Non-Black candidates were listed preemptively nearly twice as frequently as Black candidates in 2019 (38% vs. 21% preemptive) and at higher eGFR values (median 15.6 vs. 15.0 ml/min per 1.73 m2). After adjusting for candidate characteristics, including listing eGFR without the race coefficient, preemptive Black candidates still had significantly lower odds of preemptive deceased donor (DD) kidney transplantation compared to non-Black candidates (odds ratio 0.87, 95% confidence interval: 0.78-0.98). Conclusions: Over the last 2 decades, Black patients were consistently less likely to be listed preemptively and were listed at lower eGFR values. Adjusting for listing eGFR with the race coefficient computationally removed did not eliminate the racial disparity, suggesting that additional efforts are needed to achieve equity in preemptive transplantation beyond adopting race-free eGFR equations.

Effects of Delayed Graft Function on Transplant Outcomes: A Meta-analysis.

Delayed graft function (DGF) is a frequent complication of kidney transplantation, but its impact on long- and short-term transplant outcomes is unclear. We conducted a systematic literature search for studies published from 2007 to 2020 investigating the association between DGF and posttransplant outcomes. Forest plots stratified between center studies and registry studies were created with pooled odds ratios. Posttransplant outcomes including graft failure, acute rejection, patient mortality, and kidney function were analyzed. Of the 3422 articles reviewed, 38 papers were included in this meta-analysis. In single-center studies, patients who experienced DGF had increased graft failure (odds ratio [OR] 3.38; 95% confidence interval [CI], 1.85-6.17; P < 0.01), acute allograft rejection (OR 1.84; 95% CI, 1.30-2.61; P < 0.01), and mortality (OR 2.32; 95% CI, 1.53-3.50; P < 0.01) at 1-y posttransplant. Registry studies showed increased graft failure (OR 3.66; 95% CI, 3.04-4.40; P < 0.01) and acute rejection (OR 3.24; 95% CI, 1.88-5.59; P < 0.01) but not mortality (OR 2.27; 95% CI, 0.97-5.34; P = 0.06) at 1-y posttransplant. DGF was associated with increased odds of graft failure, acute rejection, and mortality. These results in this meta-analysis could help inform the selection process, treatment, and monitoring of transplanted kidneys at high risk of DGF.

Retrospective analysis of the impact of severe obesity on kidney transplant outcomes.

BACKGROUND: The prevalence of obesity among kidney transplant recipients is rising. We sought to determine the association between recipient body mass index (BMI) and post-transplant complications. METHODS: Single-center, retrospective cohort study of all adult kidney transplant recipients from 2004 to 2020. Recipients were stratified into four BMI categories: normal-weight (BMI 18.5-24.9 kg/m2, n = 1020), overweight (BMI 25-29.9 kg/m2, n = 1002), moderately obese (BMI 30-34.9 kg/m2, n = 510) and severely-to-morbidly obese (BMI ≥35 kg/m2, n = 274). Logistic regression was used to estimate the association between BMI category and surgical site infections (SSIs). RESULTS: Recipients with BMI ≥35 kg/m2 had significantly higher rates of SSIs (P < .0001) compared with recipients in all other categories. On multivariable analysis, recipients with BMI ≥35 kg/m2 had increased odds of SSIs compared with normal-weight recipients [odds ratio (OR) 3.34, 95% confidence interval (CI) 1.55-7.22, P = .022). On multivariable and Kaplan-Meier analyses, no BMI groups demonstrated increased odds for death-censored graft failure. CONCLUSION: Severe obesity in kidney transplant recipients is associated with increased SSIs, but not kidney allograft failure.

Monoallelic IRF5 deficiency in B cells prevents murine lupus.

Gain-of-function polymorphisms in the transcription factor IFN regulatory factor 5 (IRF5) are associated with an increased risk of developing systemic lupus erythematosus. However, the IRF5-expressing cell type(s) responsible for lupus pathogenesis in vivo is not known. We now show that monoallelic IRF5 deficiency in B cells markedly reduced disease in a murine lupus model. In contrast, similar reduction of IRF5 expression in macrophages, monocytes, and neutrophils did not reduce disease severity. B cell receptor and TLR7 signaling synergized to promote IRF5 phosphorylation and increase IRF5 protein expression, with these processes being independently regulated. This synergy increased B cell-intrinsic IL-6 and TNF-α production, both key requirements for germinal center (GC) responses, with IL-6 and TNF-α production in vitro and in vivo being substantially lower with loss of 1 allele of IRF5. Mechanistically, TLR7-dependent IRF5 nuclear translocation was reduced in B cells from IRF5-heterozygous mice. In addition, we show in multiple lupus models that IRF5 expression was dynamically regulated in vivo with increased expression in GC B cells compared with non-GC B cells and with further sequential increases during progression to plasmablasts and long-lived plasma cells. Overall, a critical threshold level of IRF5 in B cells was required to promote disease in murine lupus.

Cost-effectiveness analysis of newborn pulse oximetry screening to detect critical congenital heart disease in Colombia.

BACKGROUND: In many countries, economic assessments of the routine use of pulse oximetry in the detection of Critical Congenital Heart Disease (CCHD) at birth has not yet been carried out. CCHDs necessarily require medical intervention within the first months of life. This assessment is a priority in low and medium resource countries. The purpose of this study was to assess the cost-effectiveness (CE) relation of pulse oximetry in the detection of cases of CCHD in Colombia. METHODS: A full economic assessment of the cost-effectiveness type was conducted from the perspective of society. A decision tree was constructed to establish a comparison between newborn physical examination plus pulse oximetry, versus physical examination alone, in the diagnosis of CCHDs. The sensitivity and specificity of pulse oximetry were estimated from a systematic review of the literature; to assess resource use, micro-costing analyses and surveys were conducted. The time horizon of the economic evaluation was the first week after birth and until the first year of life. The incremental cost-effectiveness ratio (ICER) was determined and, to control for uncertainty, deterministic and probabilistic sensitivity analysis were made, including the adoption of different scenarios of budgetary impact. All costs are expressed in US dollars from 2017, using the average exchange rate for 2017 [$2,951.15 COP for 1 dollar]. RESULTS: The costs of pulse oximetry screening plus physical examination were $102; $7 higher than physical examination alone. The effectiveness of pulse oximetry plus the physical examination was 0.93; that is, 0.07 more than the physical examination on its own. The ICER was $100 for pulse oximetry screening; that is, if one wishes to increase 1% the probability of a correct CCHD diagnosis, this amount would have to be invested. A willingness to pay of $26.292 USD (direct medical cost) per probability of a correct CCHD diagnosis was assumed. CONCLUSIONS: At current rates and from the perspective of society, newborn pulse oximetry screening at 24 h in addition to physical examination, and considering a time horizon of 1 week, is a cost-effective strategy in the early diagnosis of CCHDs in Colombia.Trial registration "retrospectively registered".

Nanoparticle exposures from nano-enabled toner-based printing equipment and human health: state of science and future research needs.

Toner formulations used by laser printers (LP) and photocopiers (PC), collectively called "toner-based printing equipment" (TPE), are nano-enabled products (NEP) because they contain several engineered nanomaterials (ENM) that improve toner performance. It has been shown that during consumer use (printing), these ENM are released in the air, together with other semi-volatile organic nanoparticles, and newly formed gaseous co-pollutants such as volatile organic compounds (VOC). The aim of this review is to detail and analyze physico-chemical and morphological (PCM), as well as the toxicological properties of particulate matter (PM) emissions from TPE. The review covers evolution of science since the early 2000, when this printing technology first became a subject of public interest, as well as the lagging regulatory framework around it. Important studies that have significantly changed our understanding of these exposures are also highlighted. The review continues with a critical appraisal of the most up-to-date cellular, animal and human toxicological evidence on the potential adverse human health effects of PM emitted from TPE. We highlight several limitations of existing studies, including (i) use of high and often unrealistic doses in vitro or in vivo; (ii) unrealistically high-dose rates in intratracheal instillation studies; (iii) improper use of toners as surrogate for emitted nanoparticles; (iv) lack of or inadequate PCM characterization of exposures; and (v) lack of dosimetry considerations in in vitro studies. Presently, there is compelling evidence that the PM0.1 from TPE are biologically active and capable of inducing oxidative stress in vitro and in vivo, respiratory tract inflammation in vivo (in rats) and in humans, several endpoints of cellular injury in monocultures and co-cultures, including moderate epigenetic modifications in vitro. In humans, limited epidemiological studies report typically 2-3 times higher prevalence of chronic cough, wheezing, nasal blockage, excessive sputum production, breathing difficulties, and shortness of breath, in copier operators relative to controls. Such symptoms can be exacerbated during chronic exposures, and in individuals susceptible to inhaled pollutants. Thus respiratory, immunological, cardiovascular, and other disorders may be developed following such exposures; however, further toxicological and larger scale molecular epidemiological studies must be done to fully understand the mechanism of action of these TPE emitted nanoparticles. Major research gaps have also been identified. Among them, a methodical risk assessment based on "real world" exposures rather than on the toner particles alone needs to be performed to provide the much-needed data to establish regulatory guidelines protective of individuals exposed to TPE emissions at both the occupational and consumer level. Industry-wide molecular epidemiology as well as mechanistic animal and human studies are also urgently needed.

Estabelecimento in vitro de explantes de três cultivares de bananeira / Explants establishment in vitro of three banana cultivars

O objetivo do presente trabalho foi avaliar dois protocolos de desinfestação na micropropagação em três cultivares de bananeira. Utilizaram-se mudas das cultivares de bananeira Prata Anã, FHIA 18 e SH3640. Os protocolos 1 e 2 de desinfestação (Des. 1 e Des. 2) foram realizados utilizando-se os seguintes produtos: solução fungicida de Derosol, álcool comercial, solução de hipoclorito de sódio e de hipoclorito de cálcio e tween 20, apresentando variações na concentração dos produtos em cada um dos protocolos. As avaliações para a porcentagem de contaminação foram realizadas diariamente por meio do número total de tubos contaminados e não contaminados. O delineamento foi em blocos casualizados, com quatro repetições, em um sistema fatorial. As contaminações que ocorreram foram causadas exclusivamente por bactérias. Independentemente do tratamento utilizado, os índices de contaminação foram superiores a 29 por cento para as três cultivares testadas. Estes resultados indicam a necessidade de adequar novas metodologias de assepsias de explantes de bananeira.

The purpose of this work was to evaluate two protocols of disinfestations in the micropropagation on young plants of three banana cultivars: Prata-Anã, FHIA 18 and SH3640. Protocols 1 and 2 of disinfestations (Dis. 1 and Dis. 2) were carried out using the products: fungicidal solution of Derosol, commercial alcohol, solution of sodium hypo chlorite and calcium hypo chlorite and tween 20, presenting variations in their concentration in every one of the protocols. The evaluations for contamination rate were taken daily by means of the total number of contaminated and non-contaminated tubes. A random block design in a factorial scheme with four repetitions was used. Exclusively bacteria had caused all contamination. Independently of the used treatment the contamination levels had been up to 29 percent for all the three cultivars tested. These results indicate the necessity of adjusting the new methodologies of asepses of banana explants.