Successful implementation of prophylactic veno-venoarterial extracorporeal membrane oxygenation in high-risk trauma surgery: A case report.

INTRODUCTION: Extracorporeal Membrane Oxygenation (ECMO) is increasingly utilized in trauma care, yet its elective use during high-risk surgeries remains unreported. CASE REPORT: We report a successful instance of prophylactic ECMO support via a Veno-Venoarterial (V-VA) configuration during high-risk surgery in a patient with extensive trauma, including severe thoracic damage and a highly unstable thoracic spine fracture. V-VA ECMO prevented complications such as hemodynamic and respiratory collapse associated with chest compression during the surgical procedure, as the patient should be in a prone position. DISCUSSION: The potential of ECMO as prophylactic support in high-risk surgery amongst trauma patients underscores a novel application of this technology. Complex configurations must be evaluated to avoid associated ECMO complications. CONCLUSION: Our case highlights the potential of prophylactic ECMO hybrid modes, indicating their safe application during high-risk procedures in select trauma patients.

Consenso de hemofilia en México / Mexican Consensus in Haemophilia

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Abstract Hemophilia is a hemorrhagic disorder with a sex-linked inherited pattern, characterized by an inability to amplify coagulation due to a deficiency in coagulation factor VIII (hemophilia A or classic) or factor IX (hemophilia B). Sequencing of the genes involved in hemophilia has provided a description and record of the main mutations, as well as a correlation with the various degrees of severity. Hemorrhagic manifestations are related to levels of circulating factor, mainly affecting the musculoskeletal system and specifically the large joints (knees, ankles and elbows). This document is a review and consensus of the main genetic aspects of hemophilia, from the inheritance pattern to the concept of women carriers, physiopathology and classification of the disorder, the basic and confirmation studies when hemophilia is suspected, the various treatment regimens based on infusion of the deficient coagulation factor as well as innovative factor-free therapies and recommendations for the management of complications associated with treatment (development of inhibitors and/or transfusion transmitted infections) or secondary to articular hemorrhagic events (hemophilic arthropathy). Finally, relevant reviews of clinical and treatment aspects of hemorrhagic pathology charachterized by acquired deficiency of FVIII secondary to neutralized antibodies named acquired hemophilia.

Proton pump inhibitors and risk for recurrent ischemic events or death in outpatients with symptomatic artery disease.

BAGKGROUND AND AIMS: The influence of proton pump inhibitors (PPIs) on outcome in patients with symptomatic artery disease remains controversial. METHODS: FRENA is a prospective registry of consecutive outpatients with symptomatic coronary (CAD), cerebrovascular (CVD) or peripheral artery disease (PAD). We compared the risk for subsequent ischemic events or death according to the use of PPIs. RESULTS: As of December 2016, 5170 patients were recruited: 1793 (35%) had CAD, 1530 (30%) CVD and 1847 (35%) had PAD. Overall, 2289 patients (44%) were regularly using PPIs. During a median follow-up of 36 months, 172 patients suffered a recurrent myocardial infarction, 139 had ischemic stroke, 71 underwent limb amputation and 267 died (cardiovascular death, 109). On multivariable analysis, patients using PPIs were at a lower risk for subsequent limb amputation (hazard ratio [HR]: 0.53; 95%CI: 0.30-0.94), a similar risk for myocardial infarction (HR: 0.78; 95%CI: 0.55-1.10) or stroke (HR: 0.93; 95%CI: 0.64-1.35) and at a higher risk of death (HR: 1.37; 95%CI: 1.04-1.79). CONCLUSIONS: Among stable outpatients with symptomatic artery disease, the use of PPIs was associated with a lower risk for subsequent ischemic events but a higher risk for death.

Multivariate analysis for coronary heart disease in heterozygote familial hypercholesterolemia patients.

AIM: rs599839 polymorphism has been related with low levels of cholesterol and reduced coronary heart disease (CHD). METHODS: We investigated the frequency of this polymorphism in patients with heterozygous familial hypercholesterolemia (HeFH) in the Spanish familial hypercholesterolemia cohort, 230 with and 202 without CHD. Results & discussion: A lower G-allele prevalence was observed in HeFH patients with CHD with respect to controls, 35 versus 45%, respectively (p = 0.029), suggesting a protective effect. However, it was found that there was no association between rs599839 alleles and CHD in the multivariate analysis. CONCLUSION: The frequency of the protective G-allele of the rs599839 polymorphism was lower in HeFH patients with CHD compared with those HeFH patients without CHD. However, its role in HeFH may be masked by very high levels of cholesterol.

Long-Term Loss of Response in Proton Pump Inhibitor-Responsive Esophageal Eosinophilia Is Uncommon and Influenced by CYP2C19 Genotype and Rhinoconjunctivitis.

OBJECTIVES: Proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE) is diagnosed in at least one-third of patients with suspected eosinophilic esophagitis (EoE). We aimed to evaluate the durability and factors influencing long-term efficacy of PPI therapy. METHODS: Retrospective multicenter cohort study of patients with PPI-REE who had at least 12 months of follow-up. PPI therapy was tapered to the lowest dose, which maintained clinical remission. Primary outcomes were the proportion of patients with loss of histological response (<15 eos/HPF) and predictors of loss of response. CYP2C19 polymorphisms were determined from blood samples in a subset of patients. RESULTS: Seventy-five PPI-REE patients were included (mean follow-up 26 months (12-85)), of whom fifty-five (73%) had sustained histological remission on low-dose PPI therapy. Loss of response was significantly higher in those patients with a CYP2C19 rapid metabolizer genotype (36% vs. 6%, P = 0.01) and with rhinoconjunctivitis (40% vs. 13%, P = 0.007). On the multivariate analysis, a CYP2C19 rapid metabolizer genotype (odds ratio (OR) 12.5; 95% confidence interval (CI): 1.3-115.9) and rhinoconjunctivitis (OR 8.6; 95% CI: 1.5-48.7) were independent predictors of loss of response. Among relapsing patients, eosinophilia was limited to the distal esophagus in 14/20 (70%). Nine of ten relapsers, with distal eosinophilia, all showing a CYP2C19 rapid metabolizer genotype, regained histological remission after PPI dose intensification. CONCLUSIONS: Most PPI-REE patients remain in long-term remission on low-dose PPI therapy. CYP2C19 rapid metabolizer genotypes and rhinoconjunctivitis were independent predictors of loss of response to PPI, but patients frequently responded to PPI dose escalation.

rs1801275 Interleukin-4 receptor alpha polymorphism in familial hypercholesterolemia.

BACKGROUND: Interleukin-4 (IL-4) has been linked with atherogenic effects and some single nucleotide polymorphisms (SNPs) of the IL4/13 receptors (ILR4/13) have been associated with enhanced response to IL-4. OBJECTIVES: We investigated the frequency of SNP ILR4/13 in patients with familial hypercholesterolemia (FH) compared with control relatives without FH and their possible association with cardiovascular disease (CVD). METHODS: ILR4/13 polymorphisms were studied in 626 subjects included in the Spanish FH cohort, 408 patients with FH and 218 healthy relative control subjects. Logistic regression was used to assess the relation between SNP, clinical data, and CVD. RESULTS: A total of 143 (35%) FH patients had rs1801275 polymorphisms (AG or GG) of the IL-4Rα, whereas only 52 (24%) of the control group had these polymorphisms, P = .002. No differences were observed between the groups when the IL13RA2 rs638376 polymorphisms were analyzed. The multivariate analysis found association (odds ratio: 95% confidence interval) between CVD and smoking history (2.22: 1.30-3.80), low levels of high-density lipoprotein cholesterol (1.72: 1.07-2.75), hypertension (2.25: 1.32-3.85), age > 60 years (2.50: 1.52-4.07), and FH diagnosis (13.1: 6.65-26), but not with IL-4Rα rs1801275 polymorphisms. CONCLUSION: Our data suggest that SNP of IL-4Rα is more frequent in FH patients than in the relative controls. Conversely to the general population, IL-4 does not seems to play a role in the risk of developing CVD in FH patients.

Telmisartan improves insulin resistance in patients with low cytokine levels.

UNLABELLED: Metabolic syndrome (MS) is a disease with an inflammatory component. Telmisartan improves insulin resistance in MS, but its relationship with the inflammatory state is unknown. We investigated the effect of 3-month telmisartan therapy on homeostatic model assessment-insulin resistance (HOMA-IR) in hypertensive subjects with MS with regard to the levels of circulating plasma cytokines. METHODS: A total of 42 patients were included in this study; 30 were men (71%), aged 50 ± 8.2 years (mean ± SD). Cytokines and metabolic parameters were analyzed before and after treatment with telmisartan. RESULTS: Twenty-eight patients showed low plasma levels of cytokines (group 1) similar to control subjects, and 14 showed high levels (group 2). Treatment with telmisartan diminished by 35% HOMA-IR in group 1 (4.5 ± 3.1 vs 2.9 ± 2.1), without improvement in group 2. In the multivariate analysis, the predictors of improvement of HOMA-IR in response to telmisartan treatment were low levels of cytokines, whereas systolic and diastolic blood pressure and the elevation of high-sensitivity C-reactive protein had a negative effect. CONCLUSIONS: Our study provides evidence of a more favorable effect of telmisartan on glucose homeostasis in patients with MS and low levels of serum cytokines.

Treatment of cells with n-alpha-tosyl-L-phenylalanine-chloromethyl ketone induces the proteolytic loss of STAT6 transcription factor.

The implication of the STAT6 transcription factor in several human diseases makes the regulation of its activity a topic of great biological interest. The activation of this transcription factor is tightly regulated by kinases, phosphatases, and proteases. The initial aim of this study was to investigate the utility of protease inhibitors in controlling STAT6 activation. Among all inhibitors analyzed, n-alpha-tosyl-L-phenylalanine-chloromethyl ketone (TPCK) was found to inhibit the IL-4-induced STAT6 activation. Unexpectedly, this inhibition was accompanied by a loss of STAT6 protein. Thus, TPCK promoted the loss of STAT6 by a mechanism sensitive to the serine-protease inhibitor 4-(2-aminoetyl)-benzenesulfonyl fluoride. However, the effects of TPCK seemed not to be mediated by its protease inhibitory activity since multiple protease inhibitors tested had no effect on STAT6 expression. The results found suggest that the effect of TPCK was mediated by its alkylating activity. Thus, cysteine reactive and thiol antioxidant compounds prevented the loss of STAT6 induced by TPCK. The reactivity of thiol groups on STAT6 was moreover demonstrated with biotinylated sulfhydryl-reactive compounds. Analysis of other signaling molecules indicated that STAT5, but not other STATs, Shc, or c-Rel, was also affected by TPCK, suggesting a common downregulatory mechanism for STAT6 and STAT5. These results reveal a novel mechanism of action of TPCK in inducing a selective loss of STAT proteins. These findings may have implications for diseases in which STAT proteins are involved.

Kaempferol inhibits IL-4-induced STAT6 activation by specifically targeting JAK3.

IL-4 is involved in several human diseases including allergies, autoimmunity, and cancer. Its effects are mainly mediated through the transcription factor STAT6. Therefore, investigation of compounds that regulate STAT6 activation is of great interest for these diseases. Natural polyphenols are compounds reported to have therapeutic properties in diseases involving IL-4 and STAT6. The aim of this study was to investigate the effect of these compounds in the activation of this transcription factor. We found that in hemopoietic cells from human and mouse origin, some flavonoids were able to inhibit the activation of STAT6 by IL-4. To identify molecular mechanisms, we focused on kaempferol, the compound that showed the greatest inhibitory effect with the lowest cell toxicity. Treatment of cells with kaempferol did not affect activation of Src kinase by IL-4 but did prevent the phosphorylation of JAK1 and JAK3. Further enzymatic analysis demonstrated that kaempferol blocked the in vitro phosphorylation activity of JAK3 without affecting JAK1, suggesting that it specifically targeted JAK3 activity. Accordingly, kaempferol had no effect on STAT6 activation in nonhemopoietic cell lines lacking JAK3, supporting its selective inhibition of IL-4 responses through type I receptors expressing JAK3 but not type II lacking this kinase. The inhibitory effect of kaempferol was also observed in IL-2 but not IL-3-mediated responses and correlated with the inhibition of MLC proliferation. These findings reveal the potential use of kaempferol as a tool for selectively controlling cell responses to IL-4 and, in general, JAK3-dependent responses.

Developmental responses of a terrestrial insect detritivore, Megaselia scalaris (Loew) to four selenium species.

Megaselia scalaris (Loew) (Diptera: Phoridae) is an important and ubiquitous terrestrial detritivore that consumes both animal and plant material. Because both plants and animals convert selenium pollutants into various forms, the relative toxicities of ecologically relevant concentrations of sodium selenate, sodium selenite, seleno-L-methionine, and Se-(methyl) selenocysteine hydrochloride to larvae were assessed in diet bioassays. In addition, ovipositional preferences of adults and developmental effects on the eggs and larvae were measured. With chronic exposure selenocysteine was the most toxic of the selenium species to the larvae (LC50: 83 microg/g wet weight), followed by seleno-L-methionine (LC50: 130 microg/g), selenate (LC50: 258 microg/g), and selenite (LC50: 392 microg/g). Ovipositing females did not discriminate between the highest treatment concentrations of any of the pollutants as compared to the controls, indicating a lack of avoidance behavior. Larval development time was significantly increased with exposure to selenate at 100 microg/g wet weight and above, selenite at 300 microg/g and above, and at 50 microg/g and 25 microg/g and above for seleno-L-methionine and selenocysteine respectively. Pupal development was not affected by any of the selenium treatments. Significant differences between male and female adult eclosion times were observed, with females eclosing later than males as selenium concentrations increased. Significant decreases in larval survival relative to controls occurred at the lowest treatment tested (100 microg/g) for both selenate and selenite and at 100 microg/g for seleno-L-methionine, and 50 microg/g for selenocysteine. The population level implications of lack of avoidance of contaminated food, and the effects of increased development times, reduced survivorship, and non-synchronized male and female emergence are discussed.