Severe neutropenia probably caused by enzalutamide and abiraterone in a prostate cancer patient.

INTRODUCTION: Abiraterone and enzalutamide are two androgen receptor pathway inhibitors approved, among others, for the treatment of metastatic castration-resistant prostate cancer in adult men whose disease has progressed on or after a docetaxel-based regimen. Although hematological effects, especially neutropenia, are one of the main complications of other oral antineoplastic drugs, these adverse effects are infrequent in the case of androgen receptor pathway inhibitors. CASE REPORT: We report the case of a patient diagnosed with metastatic castration-resistant prostate cancer who discontinued an androgen receptor pathway inhibitor due to drug-related grade 4 neutropenia. His control blood counts before enzalutamide starting were normal. After one month of treatment, he developed a grade 4 neutropenia, with complete neutrophil count recovery four weeks later. He underwent a bone marrow aspiration, which revealed normocelullar results, and enzalutamide was restarted. Three weeks later, the treatment was eventually discontinued due to neutropenia reappearance. Neutrophil count recovery was achieved one month later. Then, he started treatment with abiraterone, but two weeks later neutropenia reappeared. Abiraterone was withdrawn, and the patient recovered from neutropenia 2 weeks later. MANAGEMENT AND OUTCOMES: This case exposes not only the occurrence of rare toxicity of two individual drugs but also the description of a probable drug-class adverse event not reported before. The patient recovered from neutropenia after the androgen receptor pathway inhibitor was withdrawn, thereby supporting the diagnosis of probable drug-induced neutropenia. DISCUSSION: There is scarce evidence in the literature concerning androgen receptor pathway inhibitor-related neutropenia. However, its life-threatening potential cannot be ignored, so healthcare professionals should be warned of the possibility of the occurrence of such adverse reactions.

Biological computation through recurrence.

One of the defining features of living systems is their adaptability to changing environmental conditions. This requires organisms to extract temporal and spatial features of their environment, and use that information to compute the appropriate response. In the last two decades, a growing body of work, mainly coming from the machine learning and computational neuroscience fields, has shown that such complex information processing can be performed by recurrent networks. Temporal computations arise in these networks through the interplay between the external stimuli and the network's internal state. In this article we review our current understanding of how recurrent networks can be used by biological systems, from cells to brains, for complex information processing. Rather than focusing on sophisticated, artificial recurrent architectures such as long short-term memory (LSTM) networks, here we concentrate on simpler network structures and learning algorithms that can be expected to have been found by evolution. We also review studies showing evidence of naturally occurring recurrent networks in living organisms. Lastly, we discuss some relevant evolutionary aspects concerning the emergence of this natural computation paradigm.

Cost-effectiveness of preoperative pharmaceutical care consultations: a 5-year analysis.

OBJECTIVES: Preoperative medication errors can be prevented by screening patients through a preoperative pharmaceutical care consultation. The aim of this study was to analyse the cost-effectiveness of implementing such a consultation and to determine which patients would benefit most. METHODS: A retrospective study was conducted that included all patients who underwent a preoperative pharmacy consultation between 2016 and 2020. During this consultation, two part-time pharmacists reviewed patients' appropriate preoperative chronic medication management. All prevented errors were collected and classified by therapeutic group and type of error. A team of pharmacists and anaesthetists assigned to each prevented medication error a probability of causing an adverse event 'p', following the methodology of Nesbit et al by establishing five different 'p' values: 0, 0.01, 0.1, 0.4, and 0.6. 'p' = 1 was not considered. The cost of an adverse event was determined to be between €4124 and €6946 according to current literature, and a sensitivity analysis was performed by increasing the interval by 20% above and below. The cost of employing two part-time specialist pharmacists was estimated to be €59 142. Savings per medication error prevented were calculated as (€4124 OR €6946) × 'p'. Total savings were the sum of all costs associated with prevented medication errors. Patients on chronic medications who were in therapeutic groups with a 0.6 probability of an adverse event or who were in therapeutic groups responsible for 50% of the prevented adverse events were considered prioritisable. RESULTS: 3105 patients attended the consultation and 1179 medication errors were prevented, corresponding to 300 adverse events. 42.2% of the errors had a 'p' of 0.4. The costs avoided by this consultation ranged from €1 237 200 to €2 083 800, while the cost of its implementation was €295 710. The cost-effectiveness ratio was between €4.2 and €7.0 saved per euro invested. In the sensitivity analysis, the ratios ranged from €3.3 to €8.5 per euro invested. Fifteen different therapeutic groups accounted for 90% of the medication errors prevented. The therapeutic groups 'Agents acting on the renin-angiotensin system', 'Antidiabetics, non-insulin (excluding SGLT2)' and 'Antithrombotics: low molecular weight heparins' were responsible for 56% of the prevented adverse events. The therapeutic groups 'Antidiabetics: rapid-acting insulin' and 'Antithrombotic agents: vitamin K antagonists, low-molecular-weight heparins, or direct oral anticoagulants' had a 'p' of 0.6. Therefore, patients in six therapeutic groups should be prioritised for preoperative pharmacy counselling. CONCLUSIONS: The implementation of preoperative pharmaceutical care consultations in Spain has proven to be cost-effective. Incorporating the probability of a medication error causing an adverse event allowed the prioritisation of patients for these consultations. Patients taking anticoagulants, oral antidiabetics, rapid-acting insulins, and agents acting on the renin-angiotensin system benefited the most. This study could serve as a basis for implementing such consultations in other hospitals, as they are effective in reducing the cost of medication errors in surgical patients.

Prognostic Implications of Blood Immune-Cell Composition in Metastatic Castration-Resistant Prostate Cancer.

The prognosis for patients with metastatic castration-resistant prostate cancer (mCRPC) varies, being influenced by blood-related factors such as transcriptional profiling and immune cell ratios. We aimed to address the contribution of distinct whole blood immune cell components to the prognosis of these patients. This study analyzed pre-treatment blood samples from 152 chemotherapy-naive mCRPC patients participating in a phase 2 clinical trial (NCT02288936) and a validation cohort. We used CIBERSORT-X to quantify 22 immune cell types and assessed their prognostic significance using Kaplan-Meier and Cox regression analyses. Reduced CD8 T-cell proportions and elevated monocyte levels were substantially connected with a worse survival. High monocyte counts correlated with a median survival of 32.2 months versus 40.3 months for lower counts (HR: 1.96, 95% CI 1.11-3.45). Low CD8 T-cell levels were associated with a median survival of 31.8 months compared to 40.3 months for higher levels (HR: 1.97, 95% CI 1.11-3.5). These findings were consistent in both the trial and validation cohorts. Multivariate analysis further confirmed the independent prognostic value of CD8 T-cell counts. This study highlights the prognostic implications of specific blood immune cells, suggesting they could serve as biomarkers in mCRPC patient management and should be further explored in clinical trials.

Phase Angle as Surrogate Marker of Muscle Weakness in Kidney Transplant Candidates Referred to Prehabilitation.

Phase angle (PhA), a marker of nutritional status obtained by bioelectrical impedance analysis (BIA), is associated with the integrity of cell membranes. Damage to muscle fiber membranes can impact muscle strength, which is related to adverse outcomes in adults with advanced chronic kidney disease (CKD). The main objective of this study was to determine the usefulness of the PhA in identifying muscle weakness in candidates for kidney transplants (KTs). Secondly, it aimed to examine the associations of PhA with other parameters of body composition, exercise performance, and muscle structure. Sensitivity, specificity, and area under the receiver operating characteristics curve were used to evaluate the PhA (index test) as a biomarker of muscle weakness. Muscle strength was estimated with maximal voluntary isometric contraction of the quadriceps (MVCI-Q) of the dominant side. Muscle weakness was defined as MVIC-Q < 40% of body weight. A total of 119 patients were evaluated (mean age 63.7 years, 75.6% men). A phase angle cut-off of 5.1° was identified to classify men with a higher likelihood of having low muscle strength in upper limbs (MVIC-Q 40% of their body weight). Male KT candidates with PhA < 5.1° had poorer exercise capacity, lower muscle strength, less muscle mass, and smaller muscle size. A PhA < 5.1° was significantly associated with an eight-fold higher muscle weakness risk (OR = 8.2, 95%CI 2.3-29.2) in a binary regression model adjusted by age, frailty, and hydration status. Remarkably, PhA is an easily obtainable objective parameter in CKD patients, requiring no volitional effort from the individual. The associations of PhA with aerobic capacity, physical activity, muscle mass, and muscle size underscore its clinical relevance and potential utility in the comprehensive evaluation of these patients.

Clinical and molecular spectrum of v-lesion.

Isolated v-lesion presents diagnostic stratification and clinical challenges. We characterized allograft outcomes for this entity based on post-transplant time (early: ≤1 month vs. late: >1 month) and compared its molecular phenotype with other v+ rejection forms. Using the NanoString® B-HOT panel, we analyzed 92 archival FFPE kidney biopsies from three centers: isolated v-lesion (n=23), ABMR v+ (n=26), TCMR v+ (n=10), mixed rejection v+ (n=23), and normal tissue (n=10). Six gene sets (ABMR, DSAST, ENDAT, TCMR, early/acute injury, late injury) were assessed. Early isolated v-lesions had the poorest one-year death-censored graft survival compared to late isolated v-lesions or other rejections (p=0.034). Gene set analysis showed lower TCMR-related gene expression in isolated v+ groups than TCMR and mixed rejection (p<0.001). Both early and late isolated v-lesions had lower ABMR-related gene expression than ABMR, mixed rejection, and TCMR (p≤0.022). Late isolated v-lesions showed reduced DSAST and ENDAT gene expression versus ABMR (p≤0.046); and decreased early/acute injury gene expression than early isolated v+, ABMR, TCMR, and mixed rejection (p≤0.026). In conclusion, isolated v-lesions exhibit distinct gene expression patterns versus other rejection v+ forms. Early isolated v+ is associated with poorer prognosis and increased early/acute injury gene expression than late isolated v+, suggesting distinct etiologies.

Screening for tropical and imported infections in migrant kidney transplant candidates from the kidney transplant access consultation.

BACKGROUND AND OBJECTIVE: Kidney transplantation (KT) should be postponed in those people with active bacterial, fungal, viral and parasitic processes, since these must be treated and resolved previously. The objective of this study is to present the screening circuit implemented by the Nephrology clinic and describe the prevalence of tropical and imported infections in KT candidates born or coming from endemic areas. MATERIALS AND METHODS: Descriptive cross-sectional study, carried out in 2021. Sociodemographic and clinical variables, serological data of general infections and specific tests of tropical infectious diseases were collected. A descriptive analysis of the data was carried out. RESULTS: 67 TR candidates from Latin America (32.8%), North Africa (22.4%), Sub-Saharan Africa (14.9%) and Asia (29.9%) were included. 68.7% were men and the mean age was 48.9 ±â€¯13.5 years. After the general and specific studies, 42 (62.7%) patients were referred to the Infectious Diseases Service to complete this study or indicate treatment. 35.8% of the patients had eosinophilia, and in one case parasites were detected in feces at the time of the study. Serology for strongyloidiasis was positive in 18 (26.9%) cases, while positive serology for other tropical infections was hardly detected. 34.3% of patients had latent tuberculosis infection. CONCLUSIONS: The prevalence of tropical and imported infections in migrant candidates for RT was low, except for strongyloidiasis and latent tuberculosis infection. Its detection and treatment are essential to avoid serious complications in post-TR. To this end, the implementation of an interdisciplinary screening program from the KT access consultation is feasible, necessary and useful.

Unmet Questions About Frailty in Kidney Transplant Candidates.

Frailty occurs frequently among patients with advanced chronic kidney disease, especially among women. Assessing frailty in kidney transplant (KT) candidates is crucial for informing them about associated risks. However, there is poor agreement between frailty scales and research on their correlation with transplant outcomes. Being prefrail significantly impacts both graft and patient survival, often beginning with just 1 Fried criterion. Rather than viewing frailty as a categorical state, it should be regarded as a spectrum ranging from 1 to 5 criteria, with the risk of adverse outcomes escalating as frailty worsens. Frailty status fluctuates during the waiting period for KT; hence, a 1-time frailty evaluation is insufficient to determine risks and implement strategies for improving functional status. Further research should investigate the components of frailty that most frequently change during this waiting period and establish strategies to prevent or reverse frailty. Although careful evaluation of frail KT candidates is necessary to prevent early complications and mortality, exclusion based solely on a frailty score is unwarranted. Instead, efforts should focus on timely interventions to enhance their condition before transplantation. Although evidence is limited, exercise programs appear feasible and yield positive results. A pretransplant clinical framework encompassing multimodal prehabilitation-comprising physical therapy, nutritional measures, and psychological support-during the waiting list period may help alleviate the effects of frailty and poor fitness after KT, ultimately improving key outcomes. Despite logistical challenges, there is a pressing need for interventional trials in this area.

Complex management and descriptive cost analysis of kidney transplant candidates: a descriptive cross-sectional study.

BACKGROUND: The organisational care needs involved in accessing kidney transplant have not been described in the literature and therefore a detailed analysis thereof could help to establish a framework (including appropriate timing, investment, and costs) for the management of this population. The main objective of this study is to analyse the profile and care needs of kidney transplant candidates in a tertiary hospital and the direct costs of studying them. METHODS: A descriptive, cross-sectional study was conducted using data on a range of variables (sociodemographic and clinical characteristics, study duration, and investment in visits and supplementary tests) from 489 kidney transplant candidates evaluated in 2020. RESULTS: The comorbidity index was high (> 4 in 64.3%), with a mean of 5.6 ± 2.4. Part of the study population had certain characteristics that could hinder their access a kidney transplant: physical dependence (9.4%), emotional distress (33.5%), non-adherent behaviours (25.2%), or language barriers (9.4%). The median study duration was 6.6[3.4;14] months. The ratio of required visits to patients was 5.97:1, meaning an investment of €237.10 per patient, and the ratio of supplementary tests to patients was 3.5:1, meaning an investment of €402.96 per patient. CONCLUSIONS: The study population can be characterised as complex due to their profile and their investment in terms of time, visits, supplementary tests, and direct costs. Management based on our results involves designing work-adaptation strategies to the needs of the study population, which can lead to increased patient satisfaction, shorter waiting times, and reduced costs.

A multiscale sensorimotor model of experience-dependent behavior in a minimal organism.

To survive in ever-changing environments, living organisms need to continuously combine the ongoing external inputs they receive, representing present conditions, with their dynamical internal state, which includes influences of past experiences. It is still unclear in general, however 1) how this happens at the molecular and cellular levels and 2) how the corresponding molecular and cellular processes are integrated with the behavioral responses of the organism. Here, we address these issues by modeling mathematically a particular behavioral paradigm in a minimal model organism, namely chemotaxis in the nematode C. elegans. Specifically, we use a long-standing collection of elegant experiments on salt chemotaxis in this animal, in which the migration direction varies depending on its previous experience. Our model integrates the molecular, cellular, and organismal levels to reproduce the experimentally observed experience-dependent behavior. The model proposes specific molecular mechanisms for the encoding of current conditions and past experiences in key neurons associated with this response, predicting the behavior of various mutants associated with those molecular circuits.

Presence of metallic components in transdermal drug delivery systems and risk of skin burns. / [Artículo traducido] Presencia de partículas metálicas en parches transdérmicos de medicamentos y riesgo de quemaduras.

OBJECTIVE: Skin burns are associated with the presence of metallic components in transdermal drug delivery systems during Magnetic Resonance Imaging, cardioversion or defibrillation procedures. The aim of the study was to review the presence of metallic components in marketed products of transdermal drug delivery systems in Spain. METHOD: For each presentation, the summary of product characteristics was reviewed. If the information was not provided, manufacturers were contacted. RESULTS: We identified 59 marketed products of transdermal drug delivery systems of 12 different active substances. 59.3% of patches contained metallic components or their presence could not be ruled out. Information regarding the need to remove the patch was only included in 8 summaries of product characteristics (13.6%). A table was elaborated and included the following aspects: product, active substance, manufacturer, need to remove the patch before the exposure to magnetic or electric fields and references. CONCLUSION: More than a half of the patches at the time of the study contained metals or their absence could not be confirmed by the manufacturer. However, this information was only included in 13.6% of summaries of product characteristics.

Treatment with Rasburicase in Hospitalized Patients with Cardiorenal Syndrome: Old Treatment, New Scenario.

Cardiorenal syndrome (CRS) involves joint dysfunction of the heart and kidney. Acute forms share biochemical alterations like hyperuricaemia (HU) with tumour lysis syndrome (TLS). The mainstay treatment of acute CRS with systemic overload is diuretics, but rasburicase is used in TLS to prevent and treat hyperuricaemia. An observational, retrospective study was performed to assess the effectiveness and safety of a single dose of rasburicase in hospitalized patients with cardiorenal syndrome, worsening renal function and uric acid levels above 9 mg/dL. Rasburicase improved diuresis and systemic congestion in the 35 patients included. A total of 86% of patients did not need to undergo RRT, and early withdrawal was possible in the remaining five. Creatinine (Cr) decreased after treatment with rasburicase from a peak of 3.6 ± 1.27 to 1.79 ± 0.83 mg/dL, and the estimated glomerular filtration rate (eGFR) improved from 17 ± 8 to 41 ± 20 mL/min/1.73 m2 (p = 0.0001). The levels of N-terminal type B Brain Natriuretic Peptide (Nt-ProBNP) and C-reactive protein (CRP) were also significantly reduced. No relevant adverse events were detected. Our results show that early treatment with a dose of rasburicase in patients with CRS and severe HU is effective to improve renal function and systemic congestion, avoiding the need for sustained extrarenal clearance, regardless of comorbidities and ventricular function.

Genome-wide association study and polygenic risk scores of retinal thickness across the cognitive continuum: data from the NORFACE cohort.

BACKGROUND: Several studies have reported a relationship between retinal thickness and dementia. Therefore, optical coherence tomography (OCT) has been proposed as an early diagnosis method for Alzheimer's disease (AD). In this study, we performed a genome-wide association study (GWAS) aimed at identifying genes associated with retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) thickness assessed by OCT and exploring the relationships between the spectrum of cognitive decline (including AD and non-AD cases) and retinal thickness. METHODS: RNFL and GCIPL thickness at the macula were determined using two different OCT devices (Triton and Maestro). These determinations were tested for association with common single nucleotide polymorphism (SNPs) using adjusted linear regression models and combined using meta-analysis methods. Polygenic risk scores (PRSs) for retinal thickness and AD were generated. RESULTS: Several genetic loci affecting retinal thickness were identified across the genome in accordance with previous reports. The genetic overlap between retinal thickness and dementia, however, was weak and limited to the GCIPL layer; only those observable with all-type dementia cases were considered. CONCLUSIONS: Our study does not support the existence of a genetic link between dementia and retinal thickness.

Blood gene expression biomarkers of response to anti-TNF drugs in pediatric inflammatory bowel diseases before initiation of treatment.

BACKGROUND/AIMS: Changes in gene expression profiles among individuals with inflammatory bowel diseases (IBDs) could potentially influence the responsiveness to anti-TNF treatment. The aim of this study was to identify genes that could serve as predictors of early response to anti-TNF therapies in pediatric IBD patients prior to the initiation of treatment. METHODS: We conducted a prospective, longitudinal, and multicenter study, enrolling 24 pediatric IBD patients aged less than 18 years who were initiating treatment with either infliximab or adalimumab. RNA-seq from blood samples was analyzed using the DESeq2 library by comparing responders and non-responders to anti-TNF drugs. RESULTS: Bioinformatic analyses unveiled 102 differentially expressed genes, with 99 genes exhibiting higher expression in responders compared to non-responders prior to the initiation of anti-TNF therapy. Functional enrichment analyses highlighted defense response to Gram-negative bacteria (FDR = 2.3 ×10-7) as the most significant biological processes, and hemoglobin binding (FDR = 0.002), as the most significant molecular function. Gene Set Enrichment Analysis (GSEA) revealed notable enrichment in transcriptional misregulation in cancer (FDR = 0.016). Notably, 13 genes (CEACAM8, CEACAM6, CILP2, COL17A1, OLFM4, INHBA, LCN2, LTF, MMP8, DEFA4, PRTN3, AZU1, and ELANE) were selected for validation, and a consistent trend of increased expression in responders prior to drug administration was observed for most of these genes, with findings for 4 of them being statistically significant (CEACAM8, LCN2, LTF2, and PRTN3). CONCLUSIONS: We identified 102 differentially expressed genes involved in the response to anti-TNF drugs in children with IBDs and validated CEACAM8, LCN2, LTF2, and PRTN3. Genes participating in defense response to Gram-negative bacterium, serine-type endopeptidase activity, and transcriptional misregulation in cancer are good candidates for anticipating the response to anti-TNF drugs in children with IBDs.

Recurrence of membranous nephropathy after kidney transplantation: A multicenter retrospective cohort study.

Membranous nephropathy (MN) is a leading cause of kidney failure worldwide and frequently recurs after transplant. Available data originated from small retrospective cohort studies or registry analyses; therefore, uncertainties remain on risk factors for MN recurrence and response to therapy. Within the Post-Transplant Glomerular Disease Consortium, we conducted a retrospective multicenter cohort study examining the MN recurrence rate, risk factors, and response to treatment. This study screened 22,921 patients across 3 continents and included 194 patients who underwent a kidney transplant due to biopsy-proven MN. The cumulative incidence of MN recurrence was 31% at 10 years posttransplant. Patients with a faster progression toward end-stage kidney disease were at higher risk of developing recurrent MN (hazard ratio [HR], 0.55 per decade; 95% confidence interval [CI], 0.35-0.88). Moreover, elevated pretransplant levels of anti-phospholipase A2 receptor (PLA2R) antibodies were strongly associated with recurrence (HR, 18.58; 95% CI, 5.37-64.27). Patients receiving rituximab for MN recurrence had a higher likelihood of achieving remission than patients receiving renin-angiotensin-aldosterone system inhibition alone. In sum, MN recurs in one-third of patients posttransplant, and measurement of serum anti-PLA2R antibody levels shortly before transplant could aid in risk-stratifying patients for MN recurrence. Moreover, patients receiving rituximab had a higher rate of treatment response.

Detection and reduction of errors in parenteral nutrition compounding through gravimetric and product control.

OBJECTIVE: To analyze the errors in the preparation of parenteral nutrition in a Pharmacy Service, detected through an already consolidated gravimetric and product quality control, and compare them with those detected during the initial years of implementing this quality control. METHODS: All errors detected through quality control in the compounding of pediatric and adult parenteral nutritions between 2019 and 2021 were prospectively analyzed. This quality control consisted of 3 sequential processes: a visual check, a gravimetric control, and a product control. Errors were classified as gravimetric, when the nutrition had a deviation of more than 5% from the theoretical weight, or as product errors when a qualitative or quantitative error was detected upon reviewing the remainder of the components used. These errors were analyzed in terms of type and the component involved. A comparison was made with the errors detected during the implementation phase of this quality control from 2016 to 2018. RESULTS: A total of 41,809 parenteral nutritions were reviewed, and 345 errors were detected (0.83% of the preparations); of these, 59 errors were found in pediatric nutritions (0.68% of them), and 286 in adult nutritions (0.86% of them). Among these errors, 193 were of gravimetric nature, while 152 were detected through product control. The main components involved in product errors were electrolytes, primarily due to the addition of excessive volumes and the use of incorrect components. A significant absolute reduction of 0.71% (P < .05) in the total number of errors was observed when compared to the implementation phase. This reduction was consistent in both gravimetric errors (-0.59%) and product-related errors (-0.12%) (P < .05). CONCLUSIONS: Comprehensive quality control of parenteral nutrition preparation is an easily implementable tool that effectively detected and prevented significant errors. Furthermore, its widespread adoption contributed to a reduction in the overall error count.

The absence of seroconversion after exposition to hepatitis C virus is not related to KIR-HLA genotype combinations (GEHEP-012 study).

BACKGROUND & AIMS: It has been reported that specific killer-cell immunoglobulin-like receptors (KIRs) and HLA genotype combinations, such as KIR2DS4/HLA-C1 with presence of KIRDL2 or KIRDL3, homozygous KIRDL3/HLA-C1 and KIR3DL1/≥2HLA-Bw4, are strongly associated with the lack of active infection and seroconversion after exposition to hepatitis C virus (HCV). OBJECTIVE: To determine whether these KIR-HLA combinations are relevant factors involved in that phenotype. PATIENTS AND METHODS: In this retrospective case-control study, genotype data from a genome-wide association study previously performed on low susceptibility to HCV-infection carried out on 27 high-risk HCV-seronegative (HRSN) individuals and 743 chronically infected (CI) subjects were used. HLA alleles were imputed using R package HIBAG v1.2223 and KIR genotypes were imputed using the online resource KIR*IMP v1.2.0. RESULTS: It was possible to successfully impute at least one KIR-HLA genotype combination previously associated with the lack of infection and seroconversion after exposition to HCV in a total of 23 (85.2%) HRSN individuals and in 650 (87.5%) CI subjects. No KIR-HLA genotype combination analyzed was related to the HRSN condition. CONCLUSIONS: Our results suggest that those KIR-HLA genotype combinations are not relevant factors involved in the lack of infection and seroconversion after exposition to HCV. More studies will be needed to completely understand this phenotype.

Tubulo-interstitial inflammation increases the risk of graft loss after the recurrence of IgA nephropathy.

Background: Immunoglobulin A nephropathy (IgAN) is the most frequent recurrent disease in kidney transplant recipients and its recurrence contributes to reducing graft survival. Several variables at the time of recurrence have been associated with a higher risk of graft loss. The presence of clinical or subclinical inflammation has been associated with a higher risk of kidney graft loss, but it is not precisely known how it influences the outcome of patients with recurrent IgAN. Methods: We performed a multicentre retrospective study including kidney transplant recipients with biopsy-proven recurrence of IgAN in which Banff and Oxford classification scores were available. 'Tubulo-interstitial inflammation' (TII) was defined when 't' or 'i' were ≥2. The main endpoint was progression to chronic kidney disease (CKD) stage 5 or to death censored-graft loss (CKD5/DCGL). Results: A total of 119 kidney transplant recipients with IgAN recurrence were included and 23 of them showed TII. Median follow-up was 102.9 months and 39 (32.8%) patients reached CKD5/DCGL. TII related to a higher risk of CKD5/DCGL (3 years 18.0% vs 45.3%, log-rank 7.588, P = .006). After multivariate analysis, TII remained related to the risk of CKD5/DCGL (HR 2.344, 95% CI 1.119-4.910, P = .024) independently of other histologic and clinical variables. Conclusions: In kidney transplant recipients with IgAN recurrence, TII contributes to increasing the risk of CKD5/DCGL independently of previously well-known variables. We suggest adding TII along with the Oxford classification to the clinical variables to identify recurrent IgAN patients at increased risk of graft loss who might benefit from intensified immunosuppression or specific IgAN therapies.

Impaired Reverse Cholesterol Transport is Associated with Changes in Fatty Acid Profile in Children and Adolescents with Abdominal Obesity.

BACKGROUND: Abdominal obesity is an important cardiovascular disease risk factor. Plasma fatty acids display a complex network of both pro and antiatherogenic effects. High density lipoproteins (HDL) carry out the antiatherogenic pathway called reverse cholesterol transport (RCT), which involves cellular cholesterol efflux (CCE), and lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities. OBJECTIVES: Our aim was to characterize RCT and its relation to fatty acids present in plasma in pediatric abdominal obesity. METHODS: Seventeen children and adolescents with abdominal obesity and 17 healthy controls were studied. Anthropometric parameters were registered. Glucose, insulin, lipid levels, CCE employing THP-1 cells, LCAT and CETP activities, plus fatty acids in apo B-depleted plasma were measured. RESULTS: The obese group showed a more atherogenic lipid profile, plus lower CCE (Mean±Standard Deviation) (6 ± 2 vs. 7 ± 2%; P < 0.05) and LCAT activity (11 ± 3 vs. 15 ±5 umol/dL.h; P < 0.05). With respect to fatty acids, the obese group showed higher myristic (1.1 ± 0.3 vs. 0.7 ± 0.3; P < 0.01) and palmitic acids (21.5 ± 2.8 vs. 19.6 ± 1.9; P < 0.05) in addition to lower linoleic acid (26.4 ± 3.3 vs. 29.9 ± 2.6; P < 0.01). Arachidonic acid correlated with CCE (r = 0.37; P < 0.05), myristic acid with LCAT (r = -0.37; P < 0.05), palmitioleic acid with CCE (r = -0.35; P < 0.05), linoleic acid with CCE (r = 0.37; P < 0.05), lauric acid with LCAT (r = 0.49; P < 0.05), myristic acid with LCAT (r = -0.37; P < 0.05) ecoisatrienoic acid with CCE (r = 0.40; P < 0.05) and lignoseric acid with LCAT (r = -0.5; P < 0.01). CONCLUSIONS: Children and adolescents with abdominal obesity presented impaired RCT, which was associated with modifications in proinflammatory fatty acids, such as palmitoleic and myristic, thus contributing to increased cardiovascular disease risk.