Plasma polyamines during pregnancy and their relationships with maternal allergies and the immune response of the neonates.

BACKGROUND: Some studies have reported that polyamine levels may influence immune system programming. The aim of this study was to evaluate the polyamine profile during gestation and its associations with maternal allergy and cytokine production in cord blood cells in response to different allergenic stimuli. METHODS: Polyamines were determined in plasma of pregnant women (24 weeks, N = 674) and in umbilical cord samples (N = 353 vein and N = 160 artery) from the Mediterranean NELA birth cohort. Immune cell populations were quantified, and the production of cytokines in response to different allergic and mitogenic stimuli was assessed in cord blood. RESULTS: Spermidine and spermine were the most prevalent polyamines in maternal, cord venous, and cord arterial plasma. Maternal allergies, especially allergic conjunctivitis, were associated with lower spermine in umbilical cord vein. Higher levels of polyamines were associated with higher lymphocyte number but lower Th2-related cells in cord venous blood. Those subjects with higher levels of circulating polyamines in cord showed lower production of inflammatory cytokines, especially IFN-α, and lower production of Th2-related cytokines, mainly IL-4 and IL-5. The effects of polyamines on Th1-related cytokines production were uncertain. CONCLUSIONS: Spermidine and spermine are the predominant polyamines in plasma of pregnant women at mid-pregnancy and also in umbilical cord. Maternal allergic diseases like allergic conjunctivitis are related to lower levels of polyamines in cord vein, which could influence the immune response of the newborn. Cord polyamine content is related to a decreased Th2 response and inflammatory cytokines production, which might be important to reduce an allergenic phenotype in the neonate.

Genome-wide association studies meta-analysis uncovers NOJO and SGS3 novel genes involved in Arabidopsis thaliana primary root development and plasticity.

BACKGROUND: Arabidopsis thaliana primary root growth has become a model for evo-devo studies due to its simplicity and facility to record cell proliferation and differentiation. To identify new genetic components relevant to primary root growth, we used a Genome-Wide Association Studies (GWAS) meta-analysis approach using data published in the last decade. In this work, we performed intra and inter-studies analyses to discover new genetic components that could participate in primary root growth. METHODS AND RESULTS: We used 639 accessions from nine different studies under control conditions and performed different GWAS tests. We found that primary root growth changes were associated with 41 genes, of which six (14.6%) have been previously described as inhibitors or promoters of primary root growth. The knockdown lines of two genes, Suppressor of Gene Silencing (SGS3), involved in tasiRNA processing, and a gene with a Sterile Alpha Motif (SAM) motif named NOJOCH MOOTS (NOJO), confirmed their role as repressors of primary root growth, none has been shown to participate in this developmental process before. CONCLUSIONS: In summary, our GWAS analysis of different available studies identified new genes that participate in primary root growth; two of them were identified as repressors of primary root growth.

Effectiveness of the Use of the Human Recombinant Epidermal Growth Factor in the Subsidized Regime vs The Contributive Regime in Patients with Venous Ulcers in Bogotá.

Introduction: Vascular ulcers constitute a serious global public health problem, responsible for causing a significant social and economic impact due to their recurrent, disabling nature and the need for prolonged therapies to cure them. Objective: To evaluate the use and efficacy of the rhEGF in the epithelialization of patients with a diagnosis of CEAP stage 6 venous insufficiency, in the two regimes of the health system in Colombia, the contributive (equivalent to a health system where citizens with payment capacity contribute a percentage of their salary) and the subsidized (equivalent to a health system where the state covers the vulnerable population and low socioeconomic level) versus the other treatments used. Methodology: Observational, descriptive, retrospective, multicenter study, in which 105 medical records with 139 ulcers were reviewed, in 2 centers, one belonging to the subsidized system and the other to the contributive system in Colombia. Results: The association with the epithelialization variable of the different treatment groups for ulcers according to the application of the mixed effect model test, for both regimes was for the Biologicals (EC 34.401/p = 0.000), Bioactive Agents (Hydrogels) (EC 24.735/p = 0.005) groups; for the rest of the treatment groups, the results were neither associated nor statistically significant. Conclusion: Intra- and perilesional therapy with rhEGF expands the therapeutic spectrum in patients with venous ulcers, regardless of the type of health system in which it will be applied, shortening the healing time and reaching a possible therapeutic goal, which according to this study there is an association with epithelialization regardless of the regime applied.

ELISA with recombinant antigen Lb6H validated for the diagnosis of American tegumentary leishmaniasis.

American tegumentary leishmaniasis (ATL) diagnosis is an open question, and the search for a solution is urgent. The available tests that detect the etiological agent of the infection are specific for ATL diagnosis. However, they present disadvantages, such as low sensitivity and the need for invasive procedures to obtain the samples. Immunological methods (leishmanin skin test and search for anti-Leishmania antibodies) are good alternatives to the etiological diagnosis of ATL. Presently, we face problems with disease confirmation due to the discontinuity in the production of leishmanin skin test antigen, particularly in resource-poor settings. Aiming to diagnose ATL, we validated rLb6H-ELISA for IgG antibodies using 1,091 samples from leishmaniasis patients and healthy controls, divided into four panels, living in 19 Brazilian endemic and non-endemic states. The rLb6H-ELISA showed a sensitivity of 98.6% and a specificity of 100.0%, with the reference panel comprising 70 ATL patient samples and 70 healthy controls. The reproducibility evaluation showed a coefficient of variation of positive samples ≤ 8.20% for repeatability, ≤ 17,97% for reproducibility, and ≤ 8.12% for homogeneity. The plates sensitized with rLb6H were stable at 4°C and -20°C for 180 days and 37°C for seven days, indicating 12 months of validity. In samples of ATL patients from five research and healthcare centers in endemic and non-endemic areas, rLb6H-ELISA showed a sensitivity of 84.0%; no significant statistical difference was observed among the five centers (chi-square test, p = 0.13). In samples of healthy controls from four areas with different endemicity, a specificity of 92.4% was obtained; lower specificity was obtained in a visceral leishmaniasis high endemicity locality (chi-square test, p<0.001). Cross-reactivity was assessed in 166 other disease samples with a positivity of 13.9%. Based on the good diagnostic performance and the reproducibility and stability of the antigen, we suggest using ELISA-rLb6H to diagnose ATL.

Vaccination against seasonal flu in childhood and adolescence. Recommendations of the Advisory Committee on Vaccines and Immunizations of the Spanish Association of Pediatrics (CAV-AEP) for the 2024-2025 season.

The flu is a constant threat that can sometimes cause severe forms of disease. The highest incidence rates by age group occur in children under 15 years of age, especially in those under 5 years, in whom the rate of hospitalization is also similar to the population aged 65 years and older. In addition, children are the main transmitters of the infection. In Spain, 5 influenza vaccines are authorized for the paediatric age group: three inactivated tetravalent vaccines harvested from fertilised eggs, one tetravalent inactivated vaccine obtained from cell cultures and one attenuated tetravalent vaccine for intranasal administration, which will become trivalent in the 2024-2025 season by excluding the B Yamagata lineage as recommended by the WHO. The CAV-AEP recommends systematic vaccination in children aged 6-59 months, children and adolescents belonging to risk groups, people who can transmit the flu to groups at risk of complicated flu, and household contacts or close family of infants under 6 months. From 2 years of age, the intranasal attenuated vaccine is preferred due to its greater acceptability and thus contribution to greater vaccination coverage. The CAV-AEP also considers that vaccination against influenza of healthy children and adolescents aged 5-18 years is advisable, as it provides individual protection and promotes protection at the family and community levels. It is especially important to vaccinate all health care professionals against influenza as well as pregnant women at any time during pregnancy.

Exploring FAST Technique for Diffusion Bonding of Tungsten to EUROFERE97 in DEMO First Wall.

The European Fusion Reactor (DEMO, Demonstration Power Plant) relies significantly on joining technologies in its design. Current research within the EUROfusion framework focuses on developing materials for the first wall and divertor applications, emphasizing the need for suitable joining processes, particularly for tungsten. The electric field-assisted sintering technique (FAST) emerges as a promising alternative due to its high current density, enabling rapid heating and cooling rates for fast sintering or joining. In this study, FAST was employed to join tungsten and EUROFERE97 steel, the chosen materials for the first wall, using 50-µm-thick Cu foils as interlayers. Three distinct joining conditions were tested at 980 °C for 2, 5, and 9 min at 41.97 MPa to optimize joint properties and assess FAST parameters influence. Hardness measurements revealed values around 450 HV0.1 for tungsten, 100 HV0.1 for copper, and 390 HV0.1 for EUROFER97 under all joining conditions. Increasing bonding time improved joint continuity along the EUROFER97/Cu and W/Cu interfaces. Notably, the 5 min bonding time resulted in the highest shear strength, while the 9 min sample exhibited reduced strength, possibly due to Kirkendall porosity accumulation at the EUROFER97/Cu interface. This porosity facilitated crack initiation and propagation, diminishing interfacial adhesion properties.

Design of Wearable Textile Electrodes for the Monitorization of Patients with Heart Failure.

Heart failure is a severe medical condition with an important worldwide incidence that occurs when the heart is unable to efficiently pump the patient's blood throughout the body. The monitoring of edema in the lower limbs is one of the most efficient ways to control the evolution of the condition. Impedance spectroscopy has been proposed as an efficient technique to monitor body volume in patients with heart failure. It is necessary to research new wearable devices for remote patient monitoring, which can be easily worn by patients in a continuous way. In this work, we design and implement new wearable textile electrodes for the monitoring of edema evolution in patients with heart failure. Impedance spectroscopy measurements were carried out in 5 healthy controls and 2 patients with heart failure using our wearable electrodes for 3 days. The results show the appropriateness of impedance spectroscopy and our wearable electrodes to monitor body volume evolution. Impedance spectroscopy is shown to be an efficient marker of the presence of edema in heart failure patients. Initial patient positive feedback was obtained for the use of the wearable device.

NIR Sensing Technologies for the Detection of Fraud in Nuts and Nut Products: A Review.

Food fraud is a major threat to the integrity of the nut supply chain. Strategies using a wide range of analytical techniques have been developed over the past few years to detect fraud and to assure the quality, safety, and authenticity of nut products. However, most of these techniques present the limitations of being slow and destructive and entailing a high cost per analysis. Nevertheless, near-infrared (NIR) spectroscopy and NIR imaging techniques represent a suitable non-destructive alternative to prevent fraud in the nut industry with the advantages of a high throughput and low cost per analysis. This review collects and includes all major findings of all of the published studies focused on the application of NIR spectroscopy and NIR imaging technologies to detect fraud in the nut supply chain from 2018 onwards. The results suggest that NIR spectroscopy and NIR imaging are suitable technologies to detect the main types of fraud in nuts.

A Search for New Biological Pathways in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy by Proteomic Research.

Background/Objectives: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary small vessel disease leading to significant morbidity and mortality. Despite advances in genetic diagnosis, the underlying pathophysiology remains incompletely understood. Proteomic studies offer insights into disease mechanisms by identifying altered protein expression patterns. Here, we conducted a proteomic analysis to elucidate molecular pathways associated with CADASIL. Methods: We enrolled genetically diagnosed CADASIL patients and healthy, genetically related controls. Plasma samples were subjected to proteomic analysis using the Olink platform, measuring 552 proteins across six panels. The data were analyzed from several approaches by using three different statistical methods: Exploratory Principal Component Analysis (PCA) and Partial Least Squares-Discriminant Analysis (PLS-DA), differential expression with moderated t-test, and gene set enrichment analysis (GSEA). In addition, bioinformatics analysis, including volcano plot, heatmap, and Variable Importance on Projection (VIP) scores from the PLS-DA model were drawn. Results: Significant differences in protein expression were observed between CADASIL patients and controls. RSPO1 and FGF-19 exhibited elevated levels (p < 0.05), while PPY showed downregulation (p < 0.05) in CADASIL patients, suggesting their involvement in disease pathogenesis. Furthermore, MIC-A/B expression varied significantly between patients with mutations in exon 4 versus exon 11 of the NOTCH3 gene (p < 0.05), highlighting potential immunological mechanisms underlying CADASIL. We identified altered pathways using GSEA, applied after ranking the study data. Conclusions: Our study provides novel insights into the proteomic profile of CADASIL, identifying dysregulated proteins associated with vascular pathology, metabolic dysregulation, and immune activation. These findings contribute to a deeper understanding of CADASIL pathophysiology and may inform the development of targeted therapeutic strategies. Further research is warranted to validate these biomarkers and elucidate their functional roles in disease progression.

Use of probiotics in preventing and treating excess weight and obesity. A systematic review.

Background: The prevalence of excess weight and obesity is increasing in an extremely concerning manner worldwide, with highly diverse therapies for current treatment. This review evaluated the scientific evidence of the past 10 years on the use of probiotics in treating excess weight and obesity in the absence of dieting. Materials: A systematic review was conducted by searching for clinical trials on humans published in English in the PubMed, Scopus and Cochrane Central databases, using the combination of keywords "Overweight", "Probiotics" and "Obesity", and published between 2012 and 2022. Results: Six published studies met the inclusion criteria. The review showed that, although there is a lack of consensus in the literature, the use of probiotics in the absence of dieting produced a significant reduction in body weight and body mass index in 66.6% of the reviewed studies, a significant reduction in waist circumference in 80.0% of the reviewed studies, and an improvement in total body fat mass and waist circumference. Conclusions: This review showed evidence of a trend in preventing body weight gain and reducing weight through the use of probiotics in individuals with excess weight or obesity. A combination of various strains of the genera Bifidobacterium and Lactobacillus was the most effective.

Increased reactivity of the paraventricular nucleus of the hypothalamus and decreased threat responding in male rats following psilocin administration.

Psychedelics have experienced renewed interest following positive clinical effects, however the neurobiological mechanisms underlying effects remain unclear. The paraventricular nucleus of the hypothalamus (PVN) plays an integral role in stress response, autonomic function, social behavior, and other affective processes. We investigated the effect of psilocin, the psychoactive metabolite of psilocybin, on PVN reactivity in Sprague Dawley rats. Psilocin increased stimulus-independent PVN activity as measured by c-Fos expression in male and female rats. Psilocin increased PVN reactivity to an aversive air-puff stimulus in males but not females. Reactivity was restored at 2- and 7-days post-injection with no group differences. Additionally, prior psilocin injection did not affect PVN reactivity following acute restraint stress. Experimental groups sub-classified by baseline threat responding indicate that increased male PVN reactivity is driven by active threat responders. These findings identify the PVN as a significant site of psychedelic drug action with implications for threat responding behavior.

Esofagitis disecante supeEsofagitis disecante superficial: dos casos de una misma entidad poco frecuente / Esophagitis dissecans superficialis: two cases of the same rare entity

La esofagitis disecante superficial (EDS) es una entidad infrecuente que se caracteriza endoscópicamente por el desprendimiento de las capas superficiales del epitelio esofágico e, histológicamente, por el aspecto bitonal del epitelio escamoso esofágico secundario a la necrosis de los estratos más superficiales. La etiología es desconocida, aunque se ha asociado con la ingesta de determinados fármacos, enfermedades autoinmunes, estasis esofágica y procedimientos endoscópicos. Presentamos dos casos: uno de ellos acontece en una mujer tras un episodio de disfagia abrupta y el segundo en un varón con comorbilidades y clínica de dolor epigástrico. La EDS es una patología que hay que considerar en su adecuado contexto clínico y endoscópico, ya que su curso es autolimitado en comparación con otras entidades de evolución tórpida o que precisan un tratamiento específico. (AU)

Esophagitis dissecans superficialis (EDS) is a rare disease characterized by sloughing of the superficial esophageal mucosa and, histologically, by the bitonal appearance of the squamous epithelium secondary to necrosis of the most superficial layers. Etiology is uncertain, however, it has been associated with some medications, autoimmune diseases, esophageal stasis and endoscopic procedures. Here, two cases are presented, one of them which appeared in a woman after an episode of dysphagia and another one which occurred to a man with comorbidities and epigastric pain. This entity should be considered due to its self-limiting clinical course, compared to other entities with a more torpid evolution or that require more specific treatment. (AU)

Circulating free insulin-like growth factor-I and prostate cancer: a case-control study nested in the European prospective investigation into cancer and nutrition.

BACKGROUND: Circulating total insulin-like growth factor-I (IGF-I) is an established risk factor for prostate cancer. However, only a small proportion of circulating IGF-I is free or readily dissociable from IGF-binding proteins (its bioavailable form), and few studies have investigated the association of circulating free IGF-I with prostate cancer risk. METHODS: We analyzed data from 767 prostate cancer cases and 767 matched controls nested within the European Prospective Investigation into Cancer and Nutrition cohort, with an average of 14-years (interquartile range = 2.9) follow-up. Matching variables were study center, length of follow-up, age, and time of day and fasting duration at blood collection. Circulating free IGF-I concentration was measured in serum samples collected at recruitment visit (mean age 55 years old; standard deviation = 7.1) using an enzyme-linked immunosorbent assay (ELISA). Conditional logistic regressions were performed to examine the associations of free IGF-I with risk of prostate cancer overall and subdivided by time to diagnosis (≤ 14 and > 14 years), and tumor characteristics. RESULTS: Circulating free IGF-I concentrations (in fourths and as a continuous variable) were not associated with prostate cancer risk overall (odds ratio [OR] = 1.00 per 0.1 nmol/L increment, 95% CI: 0.99, 1.02) or by time to diagnosis, or with prostate cancer subtypes, including tumor stage and histological grade. CONCLUSIONS: Estimated circulating free IGF-I was not associated with prostate cancer risk. Further research may consider other assay methods that estimate bioavailable IGF-I to provide more insight into the well-substantiated association between circulating total IGF-I and subsequent prostate cancer risk.

Factors associated with vasoplegic shock in the postoperative period of cardiac surgery and influence on morbidity and mortality of the use of arginine vasopressin as rescue therapy.

OBJECTIVES: Analyzing associated factors with vasoplegic shock in the postoperative period of Cardiac Surgery. Analyzing the influence of vasopressin as rescue therapy to first-line treatment with norepinephrine. DESIGN: Cohort, prospective and observational study. SETTING: Main hospital Postoperative Cardiac ICU. PATIENTS: Patients undergoing cardiac surgery with subsequent ICU admission from January 2021 to December 2022. INTERVENTIONS: Record of presurgical, perioperative and ICU discharge clinical variables. MAIN VARIABLES OF INTEREST: chronic treatment, presence of vasoplegic shock, need for vasopressin, cardiopulmonary bypass time, mortality. RESULTS: 773 patients met the inclusion criteria. The average age was 67.3, with predominance of males (65.7%). Post-CPB vasoplegia was documented in 94 patients (12.2%). In multivariate analysis, vasoplegia was associated with age, female sex, presurgical creatinine levels, cardiopulmonary bypass time, lactate level upon admission to the ICU, and need for prothrombin complex transfusion. Of the patients who developed vasoplegia, 18 (19%) required rescue vasopressin, associated with pre-surgical intake of ACEIs/ARBs, worse Euroscore score and longer cardiopulmonary bypass time. Refractory vasoplegia with vasopressin requirement was associated with increased morbidity and mortality. CONCLUSIONS: Postcardiopulmonary bypass vasoplegia is associated with increased mortality and morbidity. Shortening cardiopulmonary bypass times and minimizing products blood transfusion could reduce its development. Removing ACEIs and ARBs prior to surgery could reduce the incidence of refractory vasoplegia requiring rescue with vasopressin. The first-line treatment is norepinephrine and rescue treatment with VSP is a good choice in refractory situations. The first-line treatment of this syndrome is norepinephrine, although rescue with vasopressin is a good complement in refractory situations.

Metabolome-associated psychological comorbidities improvement in irritable bowel syndrome patients receiving a probiotic.

Our recent randomized, placebo-controlled study in Irritable Bowel Syndrome (IBS) patients with diarrhea or alternating bowel habits showed that the probiotic Bifidobacterium longum (BL) NCC3001 improves depression scores and decreases brain emotional reactivity. However, the involved metabolic pathways remain unclear. This analysis aimed to investigate the biochemical pathways underlying the beneficial effects of BL NCC3001 using metabolomic profiling. Patients received probiotic (1x 1010CFU, n=16) or placebo (n=19) daily for 6 weeks. Anxiety and depression were measured using the Hospital Anxiety and Depression Scale. Brain activity in response to negative emotional stimuli was assessed by functional Magnetic Resonance Imaging. Probiotic fecal abundance was quantified by qPCR. Quantitative measurement of specific panels of plasma host-microbial metabolites was performed by mass spectrometry-based metabolomics. Probiotic abundance in feces was associated with improvements in anxiety and depression scores, and a decrease in amygdala activation. The probiotic treatment increased the levels of butyric acid, tryptophan, N-acetyl tryptophan, glycine-conjugated bile acids, and free fatty acids. Butyric acid concentration correlated with lower anxiety and depression scores, and decreased amygdala activation. Furthermore, butyric acid concentration correlated with the probiotic abundance in feces. In patients with non-constipation IBS, improvements in psychological comorbidities and brain emotional reactivity were associated with an increased abundance of BL NCC3001 in feces and specific plasma metabolites, mainly butyric acid. These findings suggest the importance of a probiotic to thrive in the gut and highlight butyric acid as a potential biochemical marker linking microbial metabolism with beneficial effects on the gut-brain axis.

HDACs MADS-domain protein interaction: a case study of HDA15 and XAL1 in Arabidopsis thaliana.

Cellular behavior, cell differentiation and ontogenetic development in eukaryotes result from complex interactions between epigenetic and classic molecular genetic mechanisms, with many of these interactions still to be elucidated. Histone deacetylase enzymes (HDACs) promote the interaction of histones with DNA by compacting the nucleosome, thus causing transcriptional repression. MADS-domain transcription factors are highly conserved in eukaryotes and participate in controlling diverse developmental processes in animals and plants, as well as regulating stress responses in plants. In this work, we focused on finding out putative interactions of Arabidopsis thaliana HDACs and MADS-domain proteins using an evolutionary perspective combined with bioinformatics analyses and testing the more promising predicted interactions through classic molecular biology tools. Through bioinformatic analyses, we found similarities between HDACs proteins from different organisms, which allowed us to predict a putative protein-protein interaction between the Arabidopsis thaliana deacetylase HDA15 and the MADS-domain protein XAANTAL1 (XAL1). The results of two-hybrid and Bimolecular Fluorescence Complementation analysis demonstrated in vitro and in vivo HDA15-XAL1 interaction in the nucleus. Likely, this interaction might regulate developmental processes in plants as is the case for this type of interaction in animals.

Can resistance prehabilitation training bring additional benefits in valvular cardiac surgery? protocol for a randomized controlled trial.

INTRODUCTION: Cardiovascular diseases (CVD) are a group of illnesses that include coronary heart disease, cerebrovascular disease, congenital heart disease and deep vein thrombosis. Major surgery is often chosen as the treatment of choice for CVD. The concept of fast-track rehabilitation after surgery appeared in the 1970s. Participation in these exercise-based prehabilitation programmes may decrease postoperative complications and length of hospital stay. The primary aim of the present study is to evaluate whether the implementation of an additional resistance training (RT) prehabilitation protocol within cardiac exercises based prehabilitation can reduce intensive care unit (ICU) length of stay, postoperative complications and hospital length of stay (LOS). METHODS: A protocol of a prospective, parallel, randomised clinical trial includes 96 adult patients diagnosed with valvular pathology and who have been scheduled for surgery. The participants will be randomly assigned to two groups of 48. Control group will be treated with ventilatory and strengthening of respiratory muscles, and aerobic exercise. Experimental group, in addition, will be treated with RT of peripheral muscles. Both hospital stay and ICU stay will be assessed as main variables. Other secondary variables such as exercise capacity, quality of life and respiratory values will also be assessed. Quantitative variables will be analysed with a T-Test or ANOVA, or Mann Witney if the distribution is non-parametric. RESULTS AND CONCLUSION: This will be the first controlled clinical study focused on adding strength exercise as an additional treatment during prehabilitation. The results of this study will focus on helping to improve rehabilitation and prehabilitation protocols, considering that it is essential to maintain pulmonary training, as well as the inclusion of peripheral exercises that help people with heart disease to be in a better physical condition in order to increase their participation and sense of quality of life.

Exploring Definitions and Predictors of Response to Biologics for Severe Asthma.

BACKGROUND: Biologic effectiveness is often assessed as response, a term that eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging. OBJECTIVE: To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response. METHODS: This was a longitudinal cohort study using data from 21 countries, which shared data with the International Severe Asthma Registry. Changes in four asthma outcome domains were assessed in the 1-year period before and after biologic initiation in patients with a predefined level of prebiologic impairment. Responder cutoffs were 50% or greater reduction in exacerbation rate, 50% or greater reduction in long-term oral corticosteroid daily dose, improvement in one or more category in asthma control, and 100 mL or greater improvement in FEV1. Responders were defined using single and multiple domains. The association between prebiologic characteristics and postbiologic initiation response was examined by multivariable analysis. RESULTS: A total of 2,210 patients were included. Responder rate ranged from 80.7% (n = 566 of 701) for exacerbation response to 10.6% (n = 9 of 85) for a four-domain response. Many responders still exhibited significant impairment after biologic initiation: 46.7% (n = 206 of 441) of asthma control responders with uncontrolled asthma before the biologic still had incompletely controlled disease postbiologic initiation. Predictors of response were outcome-dependent. Lung function responders were more likely to have higher prebiologic FeNO (odds ratio = 1.20 for every 25-parts per billion increase), and shorter asthma duration (odds ratio = 0.81 for every 10-year increase in duration). Higher blood eosinophil count and the presence of type 2-related comorbidities were positively associated with higher odds of meeting long-term oral corticosteroid, control, and lung function responder criteria. CONCLUSIONS: Our findings underscore the multimodal nature of response, showing that many responders experience residual symptoms after biologic initiation and that predictors of response vary according to the outcome assessed.

Healthy lifestyle change and all-cause and cancer mortality in the European Prospective Investigation into Cancer and Nutrition cohort.

BACKGROUND: Healthy lifestyles are inversely associated with the risk of noncommunicable diseases, which are leading causes of death. However, few studies have used longitudinal data to assess the impact of changing lifestyle behaviours on all-cause and cancer mortality. METHODS: Within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, lifestyle profiles of 308,497 cancer-free adults (71% female) aged 35-70 years at recruitment across nine countries were assessed with baseline and follow-up questionnaires administered on average of 7 years apart. A healthy lifestyle index (HLI), assessed at two time points, combined information on smoking status, alcohol intake, body mass index, and physical activity, and ranged from 0 to 16 units. A change score was calculated as the difference between HLI at baseline and follow-up. Associations between HLI change and all-cause and cancer mortality were modelled with Cox regression, and the impact of changing HLI on accelerating mortality rate was estimated by rate advancement periods (RAP, in years). RESULTS: After the follow-up questionnaire, participants were followed for an average of 9.9 years, with 21,696 deaths (8407 cancer deaths) documented. Compared to participants whose HLIs remained stable (within one unit), improving HLI by more than one unit was inversely associated with all-cause and cancer mortality (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.81, 0.88; and HR: 0.87; 95% CI: 0.82, 0.92; respectively), while worsening HLI by more than one unit was associated with an increase in mortality (all-cause mortality HR: 1.26; 95% CI: 1.20, 1.33; cancer mortality HR: 1.19; 95% CI: 1.09, 1.29). Participants who worsened HLI by more than one advanced their risk of death by 1.62 (1.44, 1.96) years, while participants who improved HLI by the same amount delayed their risk of death by 1.19 (0.65, 2.32) years, compared to those with stable HLI. CONCLUSIONS: Making healthier lifestyle changes during adulthood was inversely associated with all-cause and cancer mortality and delayed risk of death. Conversely, making unhealthier lifestyle changes was positively associated with mortality and an accelerated risk of death.