Analysis of SIRT1 genetic variants in young Mexican individuals: relationships with overweight and obesity.

The high prevalence of obesity in Mexico starting from the early stages of life is concerning and represents a major public health problem. Genetic association studies have reported that single nucleotide variants (SNVs) in SIRT1, an NAD+-dependent deacetylase that plays an important role in the regulation of metabolic cellular functions, are associated with multiple metabolic disorders and the risk of obesity. In the present study, we analyzed the effect that the SNVs rs1467568 and rs7895833 of the SIRT1 gene may have on cardiometabolic risk factors in a young adult population from Mexico. A cross-sectional study was carried out with young adults between the ages of 18 and 25 who had a body mass index (BMI) greater than 18.5 kg/m2. This study included 1122 young adults who were classified into the normal weight (n = 731), overweight group (n = 277), and obesity group (n = 114) according to BMI of whom 405 and 404 volunteers were genotyped for rs1467568 and rs7895833 respectively using TaqMan probes through allelic discrimination assays. We found that the male sex carrying the G allele of rs7895833 had slightly lower BMI levels (p = 0.009). Furthermore, subjects carrying rs1467568 (G allele) showed a 34% lower probability of presenting with hyperbetalipoproteinemia where female carrying rs1467568 had lower levels of total cholesterol (p = 0.030), triglycerides (p = 0.026) and LDL cholesterol (p = 0.013). In conclusion, these findings suggest that the presence of both SNVs could have a non-risk effect against dyslipidemia in the Mexican population.

Cognitive rehabilitation program in patients with multiple sclerosis: A pilot study / Programa de rehabilitación cognitiva para pacientes con esclerosis múltiple: estudio piloto

Introduction In recent years, there has been an increase of studies dedicated to cognitive rehabilitation in patients with multiple sclerosis (MS); however, few of these analyze the impact on such variables as cognitive reserve. The study aims to explore the effects of a cognitive rehabilitation program comprising a combination of cognitive and physical exercises, as well as group sessions to improve cognitive performance, emotional state, and cognitive reserve index. Method Fifty patients with MS were subdivided into 2 groups: the control group, which performed aerobic exercise (n = 25), and the experimental group (n = 25), which participated in the integrated cognitive rehabilitation program (ICRP). All participants were evaluated 3 times (baseline, post-treatment, and long-term) with the Brief Repeatable Battery of Neuropsychological Tests, Cognitive Reserve Scale, Beck Depression Inventory, and a scale evaluating trait and state anxiety. Results Compared with the control group, patients in the experimental group showed improvements in cognitive function, with significant changes in measures of information processing speed, attention, memory, cognitive reserve index, and long-term mood. Conclusions The ICRP was effective in improving cognitive and emotional function in MS, and increased the cognitive reserve index. (AU)

Introducción En los últimos años se ha observado un interés creciente por la rehabilitación cognitiva en pacientes con esclerosis múltiple. Sin embargo, pocos estudios han analizado su impacto en variables como la reserva cognitiva. Analizamos el efecto de un programa de rehabilitación cognitiva que incluye ejercicios físicos y cognitivos, así como sesiones en grupo enfocadas a mejorar el rendimiento cognitivo, el estado emocional y el índice de reserva cognitiva. Métodos Nuestro estudio incluyó a 50 pacientes con esclerosis múltiple, divididos en 2 grupos: un grupo control (n = 25), en el que los pacientes realizaban ejercicio aeróbico, y un grupo experimental (n = 25), al que se administró un programa integral de rehabilitación cognitiva. Evaluamos a todos los pacientes en 3 momentos diferentes (al inicio, tras el tratamiento, y a largo plazo) con la Batería Neuropsicológica Breve, la Escala de Reserva Cognitiva, el Inventario de Depresión de Beck y una escala para medir la ansiedad rasgo y la ansiedad estado. Resultados Los pacientes del grupo experimental mostraron un mejor rendimiento cognitivo que los controles, con cambios significativos en medidas de velocidad de procesamiento de la información, atención, memoria, índice de reserva cognitiva y estado de ánimo a largo plazo. Conclusión Nuestros resultados demuestran la eficacia del programa de rehabilitación cognitiva para mejorar las funciones cognitiva y emocional de los pacientes con esclerosis múltiple y aumentar el índice de reserva cognitiva. (AU)

Glycemia and associated factors in a pediatric population in Mexico.

Aims: In this study, we evaluated the association of sociodemographic, lifestyle and cardiometabolic factors with blood glucose levels in children and adolescents in Mexico. Methods: An analytical cross-sectional study of 642 children and adolescents aged 6 to 19 years from different educational centers located in municipalities of the state of San Luis Potosí, Mexico, was carried out. Pearson χ2 and Spearman correlation tests and multiple linear regression models were used to evaluate the associations of the variables with glycemia. Results: The prevalence of prediabetes was 8.0% in both sexes. Male participants were more likely to develop hyperglycemia than female participants (OR 2.7, 95% CI: 1.5-5.0). The variables associated with glucose levels were male sex, high socioeconomic status, inadequate diet, high blood pressure, and increased total cholesterol, LDL cholesterol, and triglycerides, which also explained up to 15.6% (p < 0.05) of the variability in glucose concentrations. Conclusion: The detection of sociodemographic, lifestyle and cardiometabolic factors in children and adolescents will contribute to the implementation of prevention strategies for cardiometabolic diseases, among which prediabetes is common.

Agave fructans enhance the effects of fermented milk products on obesity biomarkers: a randomised trial.

Dysbiosis has been implicated in childhood obesity. Oral intake of fermented milk containing Lacticaseibacillus casei strain Shirota preserves gut microbiota (GM) diversity in children and adults. This study was a double-blind trial involving 37 overweight or obese children aged 6-10 years. Children were followed over a 6-week intervention period in which they received different fermented milk products containing L. casei Shirota: 10 in the first group received just L. casei Shirota; 13 received L. casei Shirota with 3 g/day of inulin (L. casei+inulin); and 14 received L. casei Shirota with 3 g/day of fructans from Agave salmiana (L. casei+fructans). Principal component analysis showed the relationship between microbial abundance, GM metabolites, and other obesity-related markers. Supplementation with probiotics and synbiotics improved the HDL-cholesterol levels of overweight and obese children, although no changes in body composition were detected. We observed an increase in butyrate or propionate concentrations in the L. casei+fructans group compared to the end of the intervention (P<0.03). A diminished level of ANGPTL4 within the L. casei+fructans group (P=0.04) was also found, but no differences when lipopolysaccharide-binding protein was evaluated. The FFAR2+ cell frequency decreased between baseline and at the end of 6-week intervention in L. casei+inulin (P=0.02) and L. casei+fructans groups (P=0.04). In contrast, the percentage of CD14+FFAR3+ frequency increased in the same groups (P=0.04). The L. casei Shirota with inulin or fructans modulates GM, which improves the lipid profile and changes at a molecular level, such as expression of FFAR3 and FFAR2, ANGPTL4, propionate, and butyrate. It, therefore, could be considered an interesting therapeutic possibility for treating childhood overweight and obesity. The study was registered at ClinicalTrials.gov (ID: NCT05423015).

Uricaemia and associated health determinants in a paediatric population in Mexico.

BACKGROUND AND AIM: Uric acid (UA) is a product of the catabolism of purines, and its increase in blood may be related to the development of cardiometabolic diseases. Whether UA is the result or causal determinant of the appearance of risk factors for cardiometabolic disease is not yet known. UA levels among the young student population in San Luis Potosi have increased in recent years, which may be indicative of a serious future public health concern. Therefore, the objective of this study was to evaluate the association of sociodemographic, lifestyle and cardiometabolic determinants with UA levels in children and adolescents in San Luis Potosí. METHODS AND RESULTS: A total of 730 students (54.1% female and 45.9% male, 6-19 years old) participated in the study. The subjects attended one of five public schools located in San Luis Potosí. Venous blood samples were collected, blood serum was separated by centrifugation, and UA concentrations were measured with an automated analytical platform. UA was associated with most of the independent variables studied. It presented a positive correlation with body mass index (r = 0.363, p < 0.01). Male sex, socioeconomic status, total screen time, exercise, adequate sleep, systolic blood pressure, total cholesterol, and high-density lipoprotein cholesterol explained 23%-39% (p < 0.001) of the variability of plasma concentrations of UA in children and adolescents. CONCLUSION: Early detection of these determinants will prevent future diseases. Moreover, it will help with the implementation of preventive strategies that could improve the health of this population.

[The importance of semiology and biochemistry in the diagnostic management of a peroxisomal biogenesis disorder]. / Importancia de la semiologia y la bioquimica en el abordaje diagnostico de un trastorno de la biogenesis peroxisomica.

INTRODUCTION: Peroxisomal biogenesis disorders are due to mutations in the PEX genes, which code for peroxins that are required for peroxisomal biogenesis. Clinically, they are expressed as a Zellweger syndrome spectrum, and there is a wide phenotypic variety. They are diagnosed biochemically, and confirmation is molecular. The aim of this illustrative case is to highlight the importance of the clinical features and biochemical testing in the management of a peroxisomal disease. CASE REPORT: A 3-year-old boy with neonatal hypotonia, overall developmental delay and failure to thrive and a pattern of hypomyelinating leukodystrophy in brain resonance. The suspected diagnosis was a disorder affecting the biogenesis of the peroxisomes due to having found a variant with an uncertain meaning in PEX5. The clinical features, the biochemical studies and critical analysis, however, made this diagnosis unlikely. Emphasis is placed on the management that must be applied when a Zellweger syndrome spectrum is suspected. CONCLUSION: In the case reported here, a peroxisomal biogenesis disorder was suspected owing to an exome sequencing which, on being critically analysed together with the clinical features and the biochemical findings, made a peroxisomal disease very unlikely. In cases of clinical suspicion, backed up by neuroimaging, the main diagnostic management must be based on the biochemistry analysis. Although confirmation is molecular, these tests must be interpreted with caution.

TITLE: Importancia de la semiologia y la bioquimica en el abordaje diagnostico de un trastorno de la biogenesis peroxisomica.Introduccion. Los trastornos de la biogenesis de los peroxisomas se deben a mutaciones en los genes PEX, que codifican peroxinas requeridas para la biogenesis peroxisomica. Clinicamente se expresan como un espectro del sindrome de Zellweger, y hay una amplia variedad fenotipica. Su diagnostico se realiza bioquimicamente y la confirmacion es molecular. El objetivo de este caso ilustrativo es resaltar la importancia de la clinica y de las pruebas bioquimicas en el abordaje de una enfermedad peroxisomica. Caso clinico. Niño de 3 años con hipotonia neonatal, retraso global del desarrollo y fallo de medro, con un patron en resonancia cerebral de leucodistrofia hipomielinizante, en quien se habia sospechado un trastorno de la biogenesis de los peroxisomas por encontrarse una variante de significado incierto en PEX5, pero su clinica, los estudios bioquimicos y el analisis critico de las pruebas moleculares hacian improbable este diagnostico. Se hace enfasis en el abordaje que deberia tenerse cuando se sospecha un trastorno del espectro del sindrome de Zellweger. Conclusion. En el caso descrito se sospecho un trastorno de la biogenesis de los peroxisomas por una secuenciacion exomica que, al analizarse criticamente junto con la clinica y los hallazgos bioquimicos, hacia muy poco probable una enfermedad peroxisomica. Cuando se tiene sospecha clinica y por neuroimagenes, el abordaje diagnostico principal debe partir del analisis bioquimico. Aunque la confirmacion es molecular, estas pruebas deben interpretarse con precaucion.

The inflammatory state of adipose tissue is not affected by the anti-inflammatory response of the A2a-adenosine system and miR-221/PTEN.

Obesity is a chronic inflammatory state with cytokines, adipokines, and miRNAs. The A2a-adenosine system decreases activation and cytokine release in immune cells. MiR-221 is upregulated in carcinogenesis and inflammatory processes, where its targets PTEN and ETS-1, negatively regulates the Akt pathway and induces the release of pro-inflammatory cytokines, respectively. However, the roles of the A2a-adenosine system and miR-221 in adipose tissue are unknown. The aim of this work was to evaluate the A2a-adenosine and miRNA pathways as immune modulators in adipose tissue. We collected aspirate of adipose tissue from patients with BMI < 25 kg/m2 (BMI < 25) and BMI ≥ 25 kg/m2 (BMI ≥ 25) who underwent liposuction; the adipose tissue was digested with collagenase, and then a Ficoll gradient was performed to obtain mononuclear cells from adipose tissue (MCAT). We evaluated the A2a levels by quantitative Retro-transcriptase Polymerase Chain Reaction (RT-qPCR) and flow cytometry and the A2a-adenosine function with a proliferation assay or cytokine levels in the presence or absence of NAD+, activators, and inhibitors of the system. We also analyzed miR-221, ETS-1 and PTEN levels by qRT-PCR. First, we detected that MCAT presented higher basal proliferation than mononuclear cells from peripheral blood; however, activation of the A2a receptor downregulated cell proliferation and cytokine release. Interestingly, while miR-221 was downregulated in MCAT from subjects with BMI ≥ 25 compared to BMI < 25, their targets ETS-1 and PTEN, were increased. In conclusion, the A2a-adenosine system is decreased in MCAT, but it maintains its function; moreover, miR-221 could participate in promoting inflammation in adipose tissue.

Amino acid profiles of young adults differ by sex, body mass index and insulin resistance.

BACKGROUND AND AIMS: An increase in plasma branched-chain amino acids is associated with a higher risk of developing type 2 diabetes and cardiovascular diseases. However, little is known about the basal plasma amino acid concentrations in young adults. Our aim was to determine the plasma amino acid profiles of young adults and to evaluate how these profiles were modified by sex, body mass index (BMI) and insulin resistance (IR). METHODS AND RESULTS: We performed a transversal study with 608 Mexican young adults aged 19.9 ± 2.4 years who were applicants to the Universidad Autónoma de San Luis Potosí. The subjects underwent a physical examination and provided a clinical history and a blood sample for biochemical, hormonal and amino acid analyses. The women had higher levels of arginine, aspartate and serine and lower levels of α-aminoadipic acid, cysteine, isoleucine, leucine, methionine, proline, tryptophan, tyrosine, urea and valine than the men. The obese subjects had higher levels of alanine, aspartate, cysteine, ornithine, phenylalanine, proline and tyrosine and lower levels of glycine, ornithine and serine than the normal weight subjects. Subjects with IR (defined as HOMA > 2.5) had higher levels of arginine, alanine, aspartate, isoleucine, leucine, phenylalanine, proline, tyrosine, taurine and valine than the subjects without IR. Furthermore, we identified two main groups in the subjects with obesity and/or IR; one group was composed of amino acids that positively correlated with the clinical, biochemical and hormonal parameters, whereas the second group exhibited negative correlations. CONCLUSION: This study demonstrates that young adults with obesity or IR have altered amino acid profiles characterized by an increase in alanine, aspartate, proline and tyrosine and a decrease in glycine.

Study of ß2-Glycoprotein I Polymorphisms in Patients With Chronic Renal Failure as a Predisposing Factor for the Development of Anti-ß2-Glycoprotein I Auto-Antibodies.

BACKGROUND: Immunoglobulin (Ig)A anti-ß2-glycoprotein I (aB2GP1) antibodies are associated with thrombotic events, cardiovascular morbidity, and death in dialysis patients. About 30% of patients with chronic renal disease are positive for IgA aB2GP1; however, the origin of these antibodies is unknown. It has been speculated that dialysis membranes, age, or etiology of renal base disease are possible precipitating factors, although these factors do not appear to be the source of antibodies. B2GP1 is a protein of 326 amino acids grouped into five domains. Eight polymorphisms have been described; the most important are Val/Leu247, which appears to predispose aB2GP1 antibody production in patients with anti-phospholipid syndrome, and Trp/Ser316, which appears to have protective antibody production of aB2GP1. METHODS: DNA samples from 92 patients with renal failure on hemodialysis were randomly collected with a 1:1 ratio for the positivity for IgA aB2GP1. Forty-six samples were positive for IgA aB2GP1 (group 1) and 46 negative for IgA aB2GP1 (group 2). All samples were anonymized to study polymorphism Val/Leu247 and polymorphism Trp/Ser316. RESULTS: No significant differences were observed between those who were positive or negative for IgA aB2GP1 in patients with renal failure treated with hemodialysis and the polymorphism located in codons 247 and 316. CONCLUSIONS: The two groups of patients have the same prevalence in polymorphisms 247 and 316, and therefore there appears not to be a genetic predisposition in our population. New trigger factors must be studied.

Effects of pregrazing herbage mass in late spring on enteric methane emissions, dry matter intake, and milk production of dairy cows.

Few studies have examined the effects of fresh forage quality on enteric methane (CH4) emissions of dairy cows under grazing conditions. The aim of the current study was to evaluate the effects of 2 contrasting forage qualities induced by different pregrazing herbage masses in late spring on enteric CH4 emissions and milk production of grazing dairy cows. The experiment was conducted as a crossover design with 24 lactating Holstein Friesian dairy cows randomly assigned to 1 of 2 treatments in 2 experimental periods. Each period had a duration of 3wk (2wk for diet adaptation and 1wk for measurements), and the interval between them was 2wk. Treatments consisted of 2 target pregrazing herbage masses [2,200 and 5,000kg of dry matter (DM)/ha above 3cm], generated by different regrowth periods, corresponding to low (LHM) and high (HHM) herbage mass treatments, respectively. Daily herbage allowance (Lolium perenne) for both treatments was 20kg of DM per cow measured above 3cm. Enteric CH4 emissions were individually determined during the last week of each period using the sulfur hexafluoride tracer technique. Daily herbage intakes by individual cows during the CH4 measurement weeks were estimated using the n-alkanes technique. During the CH4 measurement weeks, milk yield and body mass were determined twice daily, whereas milk composition was determined once in the week. The LHM pasture had a higher crude protein concentration, lower neutral detergent fiber and acid detergent fiber concentrations, and higher in vitro digestibility, with a lower proportion of ryegrass pseudostems, than the HHM pasture. Cows offered the LHM pasture had greater herbage (+13%) and total DM (+12%) intakes, increased milk (+13%) and energy-corrected milk (+11%) yields, and tendencies toward higher milk protein (+4.5%) and higher milk urea nitrogen (+15%) concentrations than their counterparts offered the HHM pasture. No differences were found between treatments in total daily CH4 production. However, the LHM treatment reduced enteric CH4 emissions per unit of milk yield (-11%) and enteric CH4 energy as a percentage of ingested gross energy (-9%) and tended to reduce CH4 per unit of dry matter intake (-8.2%) and energy-corrected milk yield (-10%) compared with the HHM treatment. The results from this study suggest that a grazing management that favors better quality pasture, as was the case of the LHM pasture in late spring compared with the HHM pasture, increases milk production of grazing dairy cows and reduces enteric CH4 emissions per unit of milk produced, constituting a viable CH4 mitigation strategy.

Evaluation of three fully automated immunoassay systems for detection of IgA anti-beta 2-glycoprotein I antibodies.

INTRODUCTION: In recent years, we have been witnessing increased clinical interest in the determination of IgA anti-beta 2-glycoprotein I (aB2GPI) antibodies as well as increased demand for this test. Some ELISA-based diagnostic systems for IgA aB2GPI antibodies detection are suboptimal to detect it. The aim of our study was to determine whether the diagnostic yield of modern detection systems based on automatic platforms to measure IgA aB2GPI is equivalent to that of the well-optimized ELISA-based assays. METHODS: In total, 130 patients were analyzed for IgA aB2GPI by three fully automated immunoassays using an ELISA-based assay as reference. The three systems were also analyzed for IgG aB2GPI with 58 patients. RESULTS: System 1 was able to detect IgA aB2GPI with good sensitivity and kappa index (99% and 0.72, respectively). The other two systems had also poor sensitivity (20% and 15%) and kappa index (0.10 and 0.07), respectively. On the other hand, kappa index for IgG aB2GPI was >0.89 in the three systems. CONCLUSION: Some analytical methods to detect IgA aB2GPI are suboptimal as well as some ELISA-based diagnostic systems. It is important that the scientific community work to standardize analytical methods to determine IgA aB2GPI antibodies.

Progressive increase of resistance in Enterobacteriaceae urinary isolates from kidney transplant recipients over the past decade: narrowing of the therapeutic options.

BACKGROUND: Antibiotic resistance is an emerging phenomenon in kidney transplantation (KT). METHODS: We compared species distribution and antimicrobial susceptibility patterns in 1052 isolates from urine cultures obtained in 2 different cohorts of kidney transplant recipients in a single center (Cohort A: 189 patients undergoing KT between January 2002 and December 2004 [336 isolates]; Cohort B: 115 patients undergoing KT between January 2011 and December 2013 [716 isolates]). RESULTS: Asymptomatic bacteriuria accounted for most of the isolates (86.9% in Cohort A and 92.3% in Cohort B). Klebsiella pneumoniae (9.5% vs. 15.6%), Pseudomonas aeruginosa (1.8% vs. 7.9%), and Enterobacter cloacae (0.6% vs. 3.1%) were significantly more common in Cohort B. The isolation of K. pneumoniae in Cohort B was associated with the occurrence of acute pyelonephritis (9.8% of all K. pneumoniae isolates vs. 2.8% of the remaining uropathogens; P = 0.001). Non-susceptibility rates among Enterobacteriaceae in Cohort B were higher for every class of antibiotics (P ≤ 0.003) with the exception of fosfomycin. Compared to Cohort A, significant increases were seen in isolates from Cohort B for multidrug-resistant (MDR) (43.9% vs. 67.8%, respectively; P = 0.001), extended-spectrum beta-lactamase (ESBL)-producing (6.6% vs. 26.1%; P = 0.001), and carbapenemase-producing Enterobacteriaceae strains (0.0% vs. 5.0%; P = 0.001). Such differences were mostly attributable to K. pneumoniae (as 54.5% and 13.4% of isolates in Cohort B were ESBL-producing and carbapenemase-producing, respectively). MDR isolates were responsible for 69.1% of episodes of symptomatic urinary tract infection in Cohort B. CONCLUSION: The increase in resistance rates among Enterobacteriaceae uropathogens is significant and may have an effect on KT programs.

Quantitative volcanic susceptibility analysis of Lanzarote and Chinijo Islands based on kernel density estimation via a linear diffusion process.

Risk management stakeholders in high-populated volcanic islands should be provided with the latest high-quality volcanic information. We present here the first volcanic susceptibility map of Lanzarote and Chinijo Islands and their submarine flanks based on updated chronostratigraphical and volcano structural data, as well as on the geomorphological analysis of the bathymetric data of the submarine flanks. The role of the structural elements in the volcanic susceptibility analysis has been reviewed: vents have been considered since they indicate where previous eruptions took place; eruptive fissures provide information about the stress field as they are the superficial expression of the dyke conduit; eroded dykes have been discarded since they are single non-feeder dykes intruded in deep parts of Miocene-Pliocene volcanic edifices; main faults have been taken into account only in those cases where they could modified the superficial movement of magma. The application of kernel density estimation via a linear diffusion process for the volcanic susceptibility assessment has been applied successfully to Lanzarote and could be applied to other fissure volcanic fields worldwide since the results provide information about the probable area where an eruption could take place but also about the main direction of the probable volcanic fissures.

Study of duodenal bacterial communities by 16S rRNA gene analysis in adults with active celiac disease vs non-celiac disease controls.

AIMS: Several studies have suggested that abnormalities in the small-intestinal microbiota might be involved in the development or the pathogenesis of celiac disease (CD). The objective of this study was to characterize and compare the composition of the duodenal microbiota between CD patients and non-CD controls. METHOD AND RESULTS: Bacterial communities were identified by pyrosequencing of 16S rRNA extracted from duodenal biopsies. The sequences analysis showed that the majority of the reads were classified within two phyla: Firmicutes and Proteobacteria. Bacterial richness and diversity were higher in non-CD controls than in untreated CD patients, but the differences were not statistically significant. The principal coordinates analysis revealed that bacterial communities of non-CD controls and untreated CD patients were dispersed without forming a clear group according to diagnosis of CD. CONCLUSIONS: There are no statistically significant differences in the upper small intestinal composition of bacterial communities between untreated CD patients and non-CD controls. SIGNIFICANCE AND IMPACT OF THE STUDY: This pyrosequencing analysis reveals a global picture of the duodenal microbiota that could be useful in future trials investigating the role of the microbiota in CD.

Risk Factors Associated With Early Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: Results From a Multinational Matched Case-Control Study.

Risk factors for invasive pulmonary aspergillosis (IPA) after kidney transplantation have been poorly explored. We performed a multinational case-control study that included 51 kidney transplant (KT) recipients diagnosed with early (first 180 posttransplant days) IPA at 19 institutions between 2000 and 2013. Control recipients were matched (1:1 ratio) by center and date of transplantation. Overall mortality among cases was 60.8%, and 25.0% of living recipients experienced graft loss. Pretransplant diagnosis of chronic pulmonary obstructive disease (COPD; odds ratio [OR]: 9.96; 95% confidence interval [CI]: 1.09-90.58; p = 0.041) and delayed graft function (OR: 3.40; 95% CI: 1.08-10.73; p = 0.037) were identified as independent risk factors for IPA among those variables already available in the immediate peritransplant period. The development of bloodstream infection (OR: 18.76; 95% CI: 1.04-339.37; p = 0.047) and acute graft rejection (OR: 40.73, 95% CI: 3.63-456.98; p = 0.003) within the 3 mo prior to the diagnosis of IPA acted as risk factors during the subsequent period. In conclusion, pretransplant COPD, impaired graft function and the occurrence of serious posttransplant infections may be useful to identify KT recipients at the highest risk of early IPA. Future studies should explore the potential benefit of antimold prophylaxis in this group.

Clinical Pharmacokinetics of Rifampin in Patients with Tuberculosis and Type 2 Diabetes Mellitus: Association with Biochemical and Immunological Parameters.

Tuberculosis (TB) remains a major public health issue due to the increasing incidence of type 2 diabetes mellitus (T2DM), which exacerbates the clinical course of TB and increases the risk of poor long-term outcomes. The aim of this study was to characterize the pharmacokinetics of rifampin (RIF) and its relationship with biochemical and immunological parameters in patients with TB and T2DM. The biochemical and immunological parameters were assessed on the same day that the pharmacokinetic evaluation of RIF was performed. Factors related to the metabolic syndrome that is characteristic of T2DM patients were not detected in the TB-T2DM group (where predominant malnutrition was present) or in the TB group. Percentages of CD8(+) T lymphocytes and NK cells were diminished in the TB and TB-T2DM patients, who had high tumor necrosis factor alpha (TNF-α) and low interleukin-17 (IL-17) levels compared to healthy volunteers. Delayed RIF absorption was observed in the TB and TB-T2DM patients; absorption was poor and slower in the latter group due to poor glycemic control. RIF clearance was also slower in the diabetic patients, thereby prolonging the mean residence time of RIF. There was a significant association between glycemic control, increased TNF-α serum concentrations, and RIF pharmacokinetics in the TB-T2DM patients. These altered metabolic and immune conditions may be factors to be considered in anti-TB therapy management when TB and T2DM are concurrently present.

Impact of squalene-based adjuvanted influenza vaccination on graft outcome in kidney transplant recipients.

BACKGROUND: Safety concerns have been raised about the use of adjuvanted vaccines after kidney transplantation. METHODS: We retrospectively analyzed 65 kidney transplant (KT) recipients who received ≥1 dose of influenza vaccine (pandemic or seasonal) during the 2009-2010 campaign. Participants were classified into 2 groups: those who received a squalene-based AS03- or MF59-adjuvanted vaccine ("adjuvanted vaccination" [AV] group, n = 37) and those who exclusively received non-adjuvanted vaccines ("non-adjuvanted vaccination" [NAV] group, n = 28). Primary outcomes included occurrence of biopsy-proven acute graft rejection (BPAR) and graft function at months 6 and 12 after vaccination. Patients were followed up until graft loss, death, or October 2010. RESULTS: Four episodes of BPAR occurred during post-vaccination follow-up, with no differences between the AV and NAV groups, in terms of cumulative incidence (5.4% vs. 7.1%, respectively; P = 0.581), incidence rate (0.22 vs. 0.18 episodes per 1000 transplant-days; P = 0.950), or occurrence of severe episodes (T-cell-mediated BPAR of grade ≥2a) (2.7% vs. 3.6%; P = 0.680). No between-group differences were seen in graft function after vaccination. CONCLUSION: Adjuvanted influenza vaccination in KT recipients seems to be safe regarding graft outcome.

Everolimus-based immunosuppression therapy for BK virus nephropathy.

BACKGROUND: Mammalian target of rapamycin inhibitors (mTOR-i) have been proposed as possible immunosuppressants of choice in BK virus nephropathy (BKN) because of their antiviral capacity. On this basis, in 2007, our Service proposed a conversion to everolimus (EVE)-based therapy from calcineurin inhibitors with an anti-calcineurin-free therapy protocol in those patients diagnosed of BKN. METHODS: A prospective, single-center case series study was performed. Fifteen cases of BKN were diagnosed from 2007 to the end of 2010. According to our protocol, immunosuppressant treatment was modified in 9 of these patients with suspension of mycophenolate and conversion from tacrolimus to EVE. RESULTS: The renal function achieved by our patients after the transplantation was excellent. Mean serum creatinine (sCr) achieved was 1.16 ± 0.2 mg/dL. Evolution of the renal function after BKN diagnosis and conversion to mTOR-i was positive in all the patients. sCr on diagnosis was 1.85 ± 0.22 mg/dL, sCr at the point in time of conversion to EVE was 2 ± 0.21 mg/dL, and final sCr of the follow-up was 1.6 ± 0.39 mg/dL (P = .05). BK viremia became negative in 5 of our patients and decreased more than 95% in the remaining 4. None of the patients had an acute rejection episode after the change of immunosuppressant. CONCLUSIONS: Conversion to mTOR-i-based therapy could provide an added benefit in BKN and could be an effective strategy for the decrease of the viremia and increase of graft survival in selected patients.

Linfohistiocitosis hemofagocítica asociada a infecciones virales: reto diagnóstico y dilema terapéutico / Hemophagocytic lymphohistiocytosis associated with viral infections: diagnostic challenges and therapeutic dilemmas

La linfohistiocitosis hemofagocítica es un síndrome clinicopatológico de evolución potencialmente fatal, en el que una respuesta inmune no controlada e ineficaz conduce a hiperinflamación. Puede aparecer como una enfermedad familiar o esporádica, asociado a diferentes factores desencadenantes: infecciones, neoplasias, enfermedades autoinmunes o inmunodeficiencias adquiridas, pero la asociación más consistente es con infecciones virales, especialmente el virus de Epstein-Barr. Las principales características clínicas son fiebre, disfunción hepática, coagulopatía y pancitopenia. El diagnóstico es difícil debido a la rareza de este síndrome y a la falta de especificidad de los hallazgos clínicos, sin embargo, un diagnóstico y tratamiento precoces son importantes para disminuir la mortalidad. El tratamiento debe ser dirigido al control de la enfermedad subyacente y a suprimir la respuesta inflamatoria exagerada mediante el uso de inmunosupresores (AU)

Hemophagocytic lymphohistiocytosis is a frequently fatal clinicopathologic syndrome in which an uncontrolled and ineffective immune response leads to severe hyperinflammation. It may occur as either a familial disorder or a sporadic condition in association with a variety of triggers: infections, malignancies, autoimmune diseases, and acquired immune deficiencies. However, the most consistent association is with viral infections, especially Epstein-Barr virus. The main clinical features are fever, liver dysfunction, coagulation abnormalities and pancytopenia. Early diagnosis and treatment are important to reducing mortality, but the diagnosis is difficult because of the rarity of the syndrome and the lack of specificity of the clinical findings. Treatment should be directed towards treating the underlying disease and to suppressing the exaggerated inflammatory response through the use of immunosuppressive agents (AU)