Summary
Background
Little is known about the impact of Epstein‐Barr virus (EBV) infection on clinical outcomes in adults with inflammatory bowel disease (IBD).
Aim
To evaluate seroprevalence, ...seroconversion rate and complications associated with EBV infection in an adult IBD cohort attending a tertiary care hospital in Spain between 2006 and 2016.
Methods
EBV serological status was determined. In seronegative patients, the seroconversion rate was evaluated. The complications associated with primary and latent EBV infection are described.
Results
One thousand four hundred and eighty‐three patients over the age of 17 were included in the study (mean age at EBV serological status determination was 48.3). Overall seroprevalence of EBV was 97.4% (95% CI: 96.6%‐98.2%). The seroconversion rate was 29.7% (95% CI: 16.2‐45.9) after a mean of 47.5 months. There were no differences in seroconversion rates between patients 35 years or younger and patients older than 35 years. A 66‐year‐old man, on treatment with thiopurines, developed lymphoma and a hemophagocytic syndrome during a primary EBV infection. Overall, six patients (one with primary infection and five with prior EBV infection) developed lymphoma. In three of five patients with lymphoma and thiopurine use, EBV was associated to the development of lymphoma.
Conclusions
There is a small percentage of adults with IBD at risk of primary EBV infection. The risks of seroconversion and its complications remain through adulthood. Our results suggest that, when considering the use of thiopurines in IBD, the information on EBV serological status should be taken into account at any age.
The net impact of cytomegalovirus (CMV) DNAemia on overall mortality (OM) and nonrelapse mortality (NRM) following allogeneic hematopoietic stem cell transplantation (allo‐HSCT) remains a matter of ...debate. This was a retrospective, multicenter, noninterventional study finally including 749 patients. CMV DNA monitoring was conducted by real‐time polymerase chain reaction (PCR) assays. Clinical outcomes of interest were OM and NRM through day 365 after allo‐HSCT. The cumulative incidence of CMV DNAemia in this cohort was 52.6%. A total of 306 out of 382 patients with CMV DNAemia received preemptive antiviral therapy (PET). PET use for CMV DNAemia, but not the occurrence of CMV DNAemia, taken as a qualitative variable, was associated with increased OM and NRM in univariate but not in adjusted models. A subcohort analysis including patients monitored by the COBAS Ampliprep/COBAS Taqman CMV Test showed that OM and NRM were comparable in patients in whom either low or high plasma CMV DNA threshold (<500 vs ≥500 IU/mL) was used for PET initiation. In conclusion, CMV DNAemia was not associated with increased OM and NRM in allo‐HSCT recipients. The potential impact of PET use on mortality was not proven but merits further research.
Among allogeneic hematopoietic stem cell transplant recipients, cytomegalovirus DNAemia, considered as a qualitative variable, is not associated with increased all‐cause or nonrelapse mortality, irrespective of the threshold of CMV DNA used to trigger preemptive antiviral therapy.
•Low-grade inflammation is a key factor for the development of metabolic syndrome.•Dysfunctional adipose tissue contributes to obesity-associated chronic inflammation.•Marine n-3 fatty acids can ...attenuate adipose tissue inflammation and dysfunction.•n-3 fatty acids-derived lipid mediators have potent proresolutive properties.•n-3 fatty acids-derived lipid mediators are beneficial in animal models of obesity.
The n-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) have been reported to improve obesity-associated metabolic disorders including chronic inflammation, insulin resistance and dyslipidaemia. Growing evidence exits about adipose tissue as a target in mediating the beneficial effects of these marine n-3 PUFAs in adverse metabolic syndrome manifestations. Therefore, in this manuscript we focus in reviewing the current knowledge about effects of marine n-3 PUFAs on adipose tissue metabolism and secretory functions. This scope includes n-3 PUFAs actions on adipogenesis, lipogenesis and lipolysis as well as on fatty acid oxidation and mitochondrial biogenesis. The effects of n-3 PUFAs on adipose tissue glucose uptake and insulin signaling are also summarized. Moreover, the roles of peroxisome proliferator-activated receptor γ (PPARγ) and AMPK activation in mediating n-3 PUFAs actions on adipose tissue functions are discussed. Finally, the mechanisms underlying the ability of n-3 PUFAs to prevent and/or ameliorate adipose tissue inflammation are also revised, focusing on the role of n-3 PUFAs-derived specialized proresolving lipid mediators such as resolvins, protectins and maresins.
Tissue injury secondary to surgical lesion produces profound changes in endocrine-metabolic function and defence mechanisms in the patient (inflammatory, immunological), leading to an increase in ...catabolism, immunosuppression and postoperative morbidity. The best anaesthetic and surgical technique should be capable of modulating this response, especially in major surgery, where it can be most harmful and increase patient morbidity. Many of the changes that maintain homeostasis are controlled by the hypothalamicpituitary- adrenal axis. The autonomic-adrenal response is usually immediate, compared to the hypothalamus-pituitary gland, which is slower and longer lasting. Cytokine synthesis and release are the earliest stages in the response to tissue lesion. The most frequently studied cytokines in surgical stress response are IL-6 and TNF-α. Inflammatory mediator concentrations are direct indicators of perioperative stress, while haemodynamic changes are considered the indirect indicators of this response. Multiple anaesthetic techniques have been described to modify the stress response in patients undergoing elective surgery. The aim of this review is to present clinical evidence on perioperative stress modulation with different anesthetics. We also describe a different point of view in immunomodulation with the intraoperative management of haemodynamic responses with inhalational bolus of sevoflurane or with remifentanil intravenous bolus. The effects of sevoflurane used as an inhalational bolus to counteract patients' intraoperative haemodynamic responses modulates the immune response the same than opioid remifentanil.
Abstract This paper presents information on the morphological, morphometric, and dental sex differences in the dwarf round ray Urotrygon nana. We recorded 12 morphological traits, sex, the ...distribution pattern of dermal denticles, the number of tooth rows, and the tooth shape of 466 individuals. The disc width of females ranged from 50 to 172 mm and that of males ranged from 53 to 135 mm. A neuronal classification model and a correspondence analysis showed that female disc width was 21.5% broader, and the distance from the rostrum to the anus was 17.7% longer than that of males, whereas males presented 19.5% greater distance between the nostrils, 9.7% greater preorbital snout length, 6.8% greater cloaca to caudal‐fin length, 2.7% greater interorbital distance, and 1.1% greater total length than females. The disc of adult males, including the abdominal cavity area, was densely covered with dermal denticles, which were slightly larger than those observed in females. Females presented homodont dentition with molariform teeth and a smooth lozenge‐shaped crown with rounded margins. Males exhibited homodonty but with tooth morphology variations in individuals of different sizes (from molariforms to sharper cusp teeth). There were changes in disc shape (from subcircular to oval), distribution and size of dermal denticles (more abundant and larger), and tooth shape (from molariform to monocuspid teeth) during male development, from neonates to adults. U. nana exhibited sexual dimorphism in size, disc shape, number and shape of teeth, and distribution and size of dermal denticles.
Methotrexate is the gold standard treatment in rheumatoid arthritis. Once absorbed, it is internalized in cells, where glutamate residues are added to produce polyglutamated forms, which are ...responsible for the effect of methotrexate. The aim of the current study is to determine the relationship between methotrexate triglutamate concentrations and the clinical evolution in rheumatoid arthritis patients, as well as to characterize the variability in both features to propose strategies for low‐dose methotrexate optimization. The quantification of methotrexate triglutamate concentration in red blood cells was performed through ultra‐performance liquid chromatography coupled with mass spectrometry. Polymorphisms of genes involved in the formation of polyglutamates were determined by real‐time polymerase chain reaction. A multivariate regression was performed to determine the covariates involved in the variability of methotrexate triglutamate concentrations and a population pharmacokinetics model was developed through nonlinear mixed‐effects modeling. Disease activity score changed according to methotrexate triglutamate concentrations; patients with good response to treatment had higher concentrations than moderate or nonresponding patients. The methotrexate triglutamate concentrations were related to time under treatment, dose, red blood cells, and body mass index. A 1‐compartment open model was selected to estimate the pharmacokinetic parameters; the typical total clearance (L/day) was determined as 1.45 * (body mass index/28 kg/m2) * (red blood cells/4.6 × 106 cells/μL) and the volume of distribution was 52.4 L, with an absorption rate of 0.0346/day and a fraction metabolized of 1.03%. Through the application of the model, the initial dose of methotrexate is proposed on the basis of stochastic simulations and considering methotrexate triglutamate concentrations found in responders patients.
Summary
The combination of fludarabine, cytarabine, idarubicin, and granulocyte colony‐stimulating factor (FLAG‐Ida) is widely used in relapsed/refractory acute myeloid leukaemia (AML). We ...retrospectively analysed the results of 259 adult AML patients treated as first salvage with FLAG‐Ida or FLAG‐Ida plus Gentuzumab‐Ozogamicin (FLAGO‐Ida) of the Programa Español de Tratamientos en Hematología (PETHEMA) database, developing a prognostic score system of survival in this setting (SALFLAGE score). Overall, 221 patients received FLAG‐Ida and 38 FLAGO‐Ida; 92 were older than 60 years. The complete remission (CR)/CR with incomplete blood count recovery (CRi) rate was 51%, with 9% of induction deaths. Three covariates were associated with lower CR/CRi: high‐risk cytogenetics and t(8;21) at diagnosis, no previous allogeneic stem cell transplantation (allo‐SCT) and relapse‐free interval <1 year. Allo‐SCT was performed in second CR in 60 patients (23%). The median overall survival (OS) of the entire cohort was 0·7 years, with 22% OS at 5‐years. Four independent variables were used to construct the score: cytogenetics, FLT3‐internal tandem duplication, length of relapse‐free interval and previous allo‐SCT. Using this stratification system, three groups were defined: favourable (26% of patients), intermediate (29%) and poor‐risk (45%), with an expected 5‐year OS of 52%, 26% and 7%, respectively. The SALFLAGE score discriminated a subset of patients with an acceptable long‐term outcome using FLAG‐Ida/FLAGO‐Ida regimen. The results of this retrospective analysis should be validated in independent external cohorts.
In the study, the authors evaluate the spatial distribution pattern of vermiculate electric‐ray Narcine vermiculatus using geostatistical techniques to predict its spatial distribution and indicate ...its reproduction strategy. From January 2008 to December 2009, 3333 specimens of vermiculate electric‐ray were caught. Total length (LT), sex, maturity stage, catch location and depth were recorded for each specimen. The LT of vermiculate electric‐ray ranged from 6.7–24.6 cm. The authors estimate an irregular spatial structure, with a high‐density patch (x¯= 53 ind. ha−1) located on the east coast, which concentrates 65.2% of the specimens. The high‐density patch consists mainly of large juveniles (13.3–19.5 cm LT), sub‐adults (14.0–19.8 cm LT) and young adults (14.7–21.3 cm LT). Data indicate that adults migrate to the high‐density patch to reproduce. Males reached maturity at 14.5 cm LT, whereas females reached maturity at 19.3 cm LT. Vitellogenesis in female vermiculate electric‐ray begins in June; ovulation, mating, fertilization and gestation in October and birth begins in February. This indicates an annual cycle with vitellogenesis and consecutive gestation, in females synchronized in reproduction. Fecundity was 1–8 (x¯= 4), and the sex ratio of embryos was 1:1. The birth occurred between February and April, with an average size at parturition of 6.3 cm LT. Incidental capture of sub‐adults and adults of N. vermiculatus by bottom trawls threatens the survival of this species.
Rhabdomyolysis ranges from an asymptomatic illness with elevation in the creatine kinase level to a life-threatening condition associated with extreme elevations in creatine kinase, electrolyte ...imbalances, acute renal failure and disseminated intravascular coagulation. Muscular trauma is the most common cause of rhabdomyolysis. Less common causes include muscle enzyme deficiencies, electrolyte abnormalities, infectious causes, drugs, toxins and endocrinopathies. Weakness, myalgia and tea-colored urine are the main clinical manifestations. The most sensitive laboratory finding of muscle injury is an elevated plasma creatine kinase level. The management of patients with rhabdomyolysis includes early vigorous hydration.
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