Transcriptome Analysis in Renal Transplant Biopsies Not Fulfilling Rejection Criteria

The clinical significance of renal transplant biopsies displaying borderline changes suspicious for T-cell mediated rejection (TCMR) or interstitial fibrosis and tubular atrophy (IFTA) with interstitial inflammation has not been well defined. Molecular profiling to evaluate renal transplant biopsies using microarrays has been shown to be an objective measurement that adds precision to conventional histology. We review the contribution of transcriptomic analysis in surveillance and indication biopsies with borderline changes and IFTA associated with variable degrees of inflammation. Transcriptome analysis applied to biopsies with borderline changes allows to distinguish patients with rejection from those in whom mild inflammation mainly represents a response to injury. Biopsies with IFTA and inflammation occurring in unscarred tissue display a molecular pattern similar to TCMR while biopsies with IFTA and inflammation in scarred tissue, apart from T-cell activation, also express B cell, immunoglobulin and mast cell-related genes. Additionally, patients at risk for IFTA progression can be identified by genes mainly reflecting fibroblast dysregulation and immune activation. At present, it is not well established whether the expression of rejection gene transcripts in patients with fibrosis and inflammation is the consequence of an alloimmune response, tissue damage or a combination of both

Lupus nephritis: Correlation of interstitial cells with glomerular function

Lupus nephritis: Correlation of interstitial cells with glomerular function. Mononuclear inflammatory cells were studied using monoclonal antibodies in the interstitium and glomeruli of 35 renal biopsy specimens from patients with lupus nephritis already taking immunosuppressants. The aims of this study were to assess the composition and significance of the infiltrate, and to assess correlations with immediate glomerular function and ability to predict the future course of the disease. The majority of interstitial cells were T lymphocytes and monocytes/macrophages. The number of interstitial CD4 +ve T helper/ inducer lymphocytes was greater than that of CD8 +ve T cytotoxic/ suppressor cells in only 19 out of 35 biopsies, the mean CD4:CD8 ratio being only 1.5 ± 1.2. NK cells and B lymphocytes were a minor component only. Some expression of IL-2, transferrin and C3b receptors was seen on interstitial cells, but HLA-DR expressing cells were much in excess of controls and the number of tubular cells expressing HLA-DR was also increased. The number of interstitial T cells, CD4 +ve cells and monocytes/macrophages was highly correlated with the extent of chronic damage judged by optical microscopy. There was also an association between glomerular function at biopsy and numbers of interstitial T cells, CD8 +ve cells, monocytes/macrophages and DR expressing cells. Subsequent decline in renal function, however, was associated only with numbers of monocytes/macrophages and the rather small number of C3b receptor-positive cells. The presence of tubulointerstitial immune aggregates of Ig and/or C in 63% of patients was associated with greater numbers of NK cells. As previously described, the degree of renal function at biopsy correlated with a chronicity index based on optical microscopy. No correlations were found between numbers or types (mostly monocyte/macrophages) of intraglomerular leukocytes and clinical or biopsy features, except that more proliferative types showed greater leukocyte numbers. One hypothesis consistent with our findings is that interstitial T cells and monocytes may be important determinants of pathogenesis and progression of lupus nephritis. While several mechanisms may play an initial role, interstitial monocytes may be the major factor in chronic injury

Perfil de personalidad en pacientes con trasplante renal: el modelo alternativo de los cinco factores

Background: There is limited research on personality traits that characterized kidney transplant patients. The aim of this study was to describe personality profile of kidney transplant patients using the Alternative Five Factor Model (AFFM), and compared it with the Spanish standard population. Method: Personality was assessed using the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ). A sample of 207 kidney transplant patients was matched by age and gender with 207 standard range controls. A logistic regression analyses was utilized to study the contribution of each ZKPQ dimension to describe the distinctive transplant patient’s profile. Results: Significant differences were showed in Neuroticism-Anxiety (p=.001), Aggression-Hostility (p=.009), and Activity (p=.001) dimensions, with lower scores on transplant patients compared with standard population. But Sociability (p=.024) was significantly higher on kidney transplant patients. In logistic regression analysis low scores on Neuroticism-Anxiety (p=.005) and Activity (p=.001) were the significant predictors to characterize personality traits of kidney transplant patients. Conclusions: Kidney transplant patients had a differential profile under the AFFM compared to standardrange sample, with lower scores on Neuroticism-Anxiety and Activity dimensions.Introducción: la investigación sobre rasgos de personalidad en pacientes con trasplante renal es limitada. El objetivo de este estudio fue describir el perfil de personalidad de pacientes con trasplante renal, utilizando el modelo alternativo de cinco factores (AFFM), y compararlo con población estándar española. Material y métodos: la personalidad fue evaluada mediante el Zuckerman-Kuhlman Personality Questionnaire (ZKPQ). Una muestra de 207 pacientes con trasplante renal se emparejó por edad y género con 207controles de la población estándar. El análisis de regresión logística permitió estudiar la aportación de cada dimensión del ZKPQ al perfil distintivo de los pacientes trasplantados. Resultados: aparecieron diferencias significativas en las dimensiones de Neuroticismo-Ansiedad (p=.001), Agresión-Hostilidad (p=.009) y Actividad (p=.001), con puntuaciones bajas en pacientes trasplantados en comparación con la población estándar. La sociabilidad (p=.024) fue significativamente mayor en pacientes trasplantados. En el análisis de regresión, las bajas puntuaciones en Neuroticismo-Ansiedad (p=.005) y Actividad (p=.001) fueron predictores significativos para caracterizar los rasgos de personalidad de pacientes trasplantados. Conclusiones: desde el AFFM, los pacientes con trasplante renal muestran un perfil diferente de personalidad comparado con la población estándar, con bajas puntuaciones en las dimensiones de Neuroticismo-Ansiedad y Actividad

Sindrome da lipodistrofia associada com a terapia anti-retroviral em portadores do HIV: considerações para os aspectos psicossociais

Several side effects have been strongly associated with antiretroviral therapy in HIV patients. Among them, the lipodystrophy syndrome which presents alterations in body shape with central adipose hypertrophy and peripheral lipoatrophy, reported by patients as a visible marker identifying them as HIV patients. This manuscript presents an analysis of current literature regarding the psychosocial aspects of HIV patients with lipodystrophy associated with antiretroviral therapy. The results show that the alterations in body shape can be disturbing in terms of psychosocial well being, affecting quality of life and increasing the stigma associated with the disease, with consequent disturbances in social relations. This analysis provides a preliminary review of the psychosocial aspects of lipodystrophy and further studies are needed for a better understanding of this complex syndrome, which could provide new information to be used in nursing care for HIV patients affected by this problem.Varios efectos secundarios han sido fuertemente asociados con la terapia antiretroviral en pacientes con HIV. Entre ellos, el síndrome de la lipodistrofia se presenta con alteraciones en la forma del cuerpo con hipertrofia adiposa central y lipoatrofia periférica, las cuales son reportadas por pacientes como marcas visibles que los identifica como pacientes con VIH. En este manuscrito, presentamos un análisis de literatura actual con respecto a los aspectos psicosociales de pacientes con VIH presentándose con lipodistrofia asociado con la terapia antiretroviral. Los resultados demuestran que las alteraciones de la forma del cuerpo pueden ser inquietantes en lo que se refiere al bienestar psicosocial, afectando la calidad de vida y aumentando el estigma asociado con la enfermedad, con las consiguientes dificultades en las relaciones sociales. Este análisis provee un repaso preliminar de los aspectos psicosociales de la lipodistrofia; sin embargo, otros estudios son necesarios para entender mejor este complejo síndrome, proveyendo nueva información para ser utilizada en el cuidado de enfermería para pacientes con VIH que están afectados por este problema.Diversos efeitos colaterais têm sido associados à terapia anti-retroviral em portadores da infecção pelo HIV, dentre esses, a síndrome da lipodistrofia apresentando hiperlipidemia e alterações na forma do corpo, com hipertrofia adiposa central e lipoatrofia periférica, relatada pelos pacientes como um visível marcador para a identificação de portadores da infecção pelo HIV. Este estudo consiste em análise da produção científica sobre aspectos psicossociais em portadores da infecção pelo HIV que apresentam lipodistrofia associada à utilização da terapia anti-retroviral. Os resultados mostram que alterações corporais podem ser suficientemente perturbadoras para o bem-estar psicossocial, afetando a qualidade de vida e aumentando o estigma da doença, ocasionando perturbações nas relações sociais. Esta revisão possibilita uma análise preliminar dos aspectos psicossocias da lipodistrofia; entretanto, outros estudos são necessários para o melhor entendimento desta complexa síndrome, trazendo novas informações a serem utilizadas no cuidado de enfermagem a portadores da infecção pelo HIV afetados por este problema

Progression of Interstitial Fibrosis and Tubular Atrophy in Low Immunological Risk Renal Transplants Monitored by Sequential Surveillance Biopsies : The Influence of TAC Exposure and Metabolism

The combination of tacrolimus (TAC) and mycophenolate is the most widely employed maintenance immunosuppression in renal transplants. Different surrogates of tacrolimus exposure or metabolism such as tacrolimus trough levels (TAC-C), coefficient of variation of tacrolimus (CV-TAC-C), time in therapeutic range (TTR), and tacrolimus concentration dose ratio (C/D) have been associated with graft outcomes. We explore in a cohort of low immunological risk renal transplants (n = 85) treated with TAC, mycophenolate mofetil (MMF), and steroids and then monitored by paired surveillance biopsies the association between histological lesions and TAC-C at the time of biopsy as well as CV-TAC-C, TTR, and C/D during follow up. Interstitial inflammation (i-Banff score ≥ 1) in the first surveillance biopsy was associated with TAC-C (odds ratio (OR): 0.69, 95% confidence interval (CI): 0.50-0.96; p = 0.027). In the second surveillance biopsy, inflammation was associated with time below the therapeutic range (OR: 1.05 and 95% CI: 1.01-1.10; p = 0.023). Interstitial inflammation in scarred areas (i-IFTA score ≥ 1) was not associated with surrogates of TAC exposure/metabolism. Progression of interstitial fibrosis/tubular atrophy (IF/TA) was observed in 35 cases (41.2%). Multivariate regression logistic analysis showed that mean C/D (OR: 0.48; 95% CI: 0.25-0.92; p = 0.026) and IF/TA in the first biopsy (OR: 0.43, 95% CI: 0.24-0.77, p = 0.005) were associated with IF/TA progression between biopsies. A low C/D ratio is associated with IF/TA progression, suggesting that TAC nephrotoxicity may contribute to fibrosis progression in well immunosuppressed patients. Our data support that TAC exposure is associated with inflammation in healthy kidney areas but not in scarred tissu

Fertilization with liquid swine manure increases productivity and improves the quality of Urochloa decumbens

This study aims at assessing the influence of mineral fertilization and biofertilizer from liquid swine manure (LSM) in productivity, levels of crude protein (CP), neutral detergent fiber (NDF) and Acid Detergent Fiber (ADF) of Urochloa decumbens. The experiment was carried out in a red Latosol under a Urochloa decumbens pasture, in a state of degradation with loss of vigor and forage productivity. The delineation chosen for this study was randomized blocks with six treatments (control without fertilization, control with use of mineral fertilizer and four unique concentrations of liquid swine manure biofertilizer (61 m3 ha-1, 121 m3 ha-1, 181 m3 ha-1, 241 m3 ha-1)). The application of residue has been split in two times on the surface of the soil, by means of a distributor of liquid waste with a fan-shaped application. Yield and bromatological features were evaluated for two years. Fertilization with LSM can fully replace mineral fertilizing in Urochloa decumbens pasture systems, resulting in an increase, as a result, in the dry mass yield from the dosage of 121 m3 ha-1 and the reduction in fiber content in neutral and acid detergent. The increments in yield were observed in the second year, while improvement in bromatological quality was observed from the first application of LSM

Recommendations for SARS-CoV- 2/ COVID-19 testing: a scoping review of current guidance

Background Testing used in screening, diagnosis and follow-up of COVID-19 has been a subject of debate. Several organisations have developed formal advice about testing for COVID-19 to assist in the control of the disease. We collated, delineated and appraised current worldwide recommendations about the role and applications of tests to control SARS-CoV- 2/COVID-19. Methods We searched for documents providing recommendations for COVID-19 testing in PubMed, EMBASE, LILACS, the Coronavirus Open Access Project living evidence database and relevant websites such as TRIP database, ECRI Guidelines Trust, the GIN database, from inception to 21 September 2020. Two reviewers applied the eligibility criteria to potentially relevant citations without language or geographical restrictions. We extracted data in duplicate, including assessment of methodological quality using the Appraisal of Guidelines for Research and Evaluation-II tool. Results We included 47 relevant documents and 327 recommendations about testing. Regarding the quality of the documents, we found that the domains with the lowest scores were ‘Editorial independence’ (Median=4%) and ‘Applicability’ (Median=6%). Only six documents obtained at least 50% score for the ‘Rigour of development’ domain. An important number of recommendations focused on the diagnosis of suspected cases (48%) and deisolation measures (11%). The most frequently recommended test was the reverse transcription-PCR (RT-PCR) assay (87 recommendations) and the chest CT (38 recommendations). There were 22 areas of agreement among guidance developers, including the use of RT-PCR for SARS-Cov- 2 confirmation, the limited role of bronchoscopy, the use chest CT and chest X-rays for grading severity and the co-assessment for other respiratory pathogens. Conclusion This first scoping review of recommendations for COVID-19 testing showed many limitations in the methodological quality of included guidance documents that could affect the confidence of clinicians in their implementation. Future guidance documents should incorporate a minimum set of key methodological characteristics to enhance their applicability for decision making.Instituto de Salud Carlos III 2017/CD17/00219European Social Fund 2014-2020, 'Investing in your future'Spanish Governmen

Diabetic retinopathy as an independent predictor of subclinical cardiovascular disease : Baseline results of the PRECISED study

Funding This work was supported by an Integrative Excellence Project by the Spanish Institute of Health, Instituto de Salud Carlos III, grant PIE 2013/27, CIBER CV, CIBERDEM, and the European Regional Development Fund (ERDF-FEDER). The Neurovascular Research Laboratory is part of the Spanish Stroke Research Network INVICTUS+ (RD16/0019/0021).Objective Detection of subclinical cardiovascular disease (CVD) has significant impact on the management of type 2 diabetes. We examined whether the assessment of diabetic retinopathy (DR) is useful for identifying patients at a higher risk of having silent CVD. Research design and methods Prospective case-control study comprising 200 type 2 diabetic subjects without history of clinical CVD and 60 age-matched non-diabetic subjects. The presence of subclinical CVD was examined using two parameters: (1) calcium coronary score (CACs); (2) composite of CACs >400 UA, carotid plaque ≥3 mm, carotid intima-media thickness ratio >1, or the presence of ECG changes suggestive of previous asymptomatic myocardial infarction. In addition, coronary angio-CT was performed. DR was assessed by slit-lamp biomicroscopy and retinography. Results Type 2 diabetic subjects presented higher CACs than non-diabetic control subjects (p400 (area under the receiver operating characteristic curve (AUROC) 0.76). In addition, an inverse relationship was observed between the degree of DR and CACs <10 AU. The variables independently associated with the composite measurement of subclinical CVD were age, diabetes duration, the glomerular filtration rate, microalbuminuria, and the presence of DR (AUROC 0.71). In addition, a relationship (p<0.01) was observed between the presence and degree of DR and coronary stenosis. Conclusions The presence and degree of DR is independently associated with subclinical CVD in type 2 diabetic patients. Our results lead us to propose a rationalized screening for coronary artery disease in type 2 diabetes based on prioritizing patients with DR, particularly those with moderate-severe degree

Treatment of early borderline lesions in low immunological risk kidney transplant patients : a Spanish multicenter, randomized, controlled parallel-group study protocol: the TRAINING study

Subclinical inflammation, including borderline lesions (BL), is very common (30-40%) after kidney transplantation (KT), even in low immunological risk patients, and can lead to interstitial fibrosis/tubular atrophy (IFTA) and worsening of renal function with graft loss. Few controlled studies have analyzed the therapeutic benefit of treating these BL on renal function and graft histology. Furthermore, these studies have only used bolus steroids, which may be insufficient to slow the progression of these lesions. Klotho, a transmembrane protein produced mainly in the kidney with antifibrotic properties, plays a crucial role in the senescence-inflammation binomial of kidney tissue. Systemic and local inflammation decrease renal tissue expression and soluble levels of α-klotho. It is therefore important to determine whether treatment of BL prevents a decrease in α-klotho levels, progression of IFTA, and loss of kidney function. The TRAINING study will randomize 80 patients with low immunological risk who will receive their first KT. The aim of the study is to determine whether the treatment of early BL (3rd month post-KT) with polyclonal rabbit antithymocyte globulin (Grafalon®) (6 mg/kg/day) prevents or decreases the progression of IFTA and the worsening of graft function compared to conventional therapy after two years post-KT, as well as to analyze whether treatment of BL with Grafalon® can modify the expression and levels of klotho, as well as the pro-inflammatory cytokines that regulate its expression. This phase IV investigator-driven, randomized, placebo-controlled clinical trial will examine the efficacy and safety of Grafalon® treatment in low-immunological-risk KT patients with early BL. : NCT04936282. Registered June 23, 2021, . Protocol Version 2 of 21 January 2022. Sponsor: Canary Isles Institute for Health Research Foundation, Canary Isles (FIISC). [email protected]