Fostamatinib effectiveness and safety for immune thrombocytopenia in clinical practice.

Fostamatinib, a recently approved syk inhibitor used in adult primary immune thrombocytopenia (ITP), has been shown to be safe and effective in this disorder. However, clinical trial results may not be similarly reproduced in clinical practice. Here 138 ITP patients (both primary and secondary) from 42 Spanish centers who had been treated with fostamatinib were evaluated prospectively and retrospectively. The median age of our cohort (55.8% women) was 66 years (interquartile range, IQR, 56-80 years). The median time since ITP diagnosis at fostamatinib initiation was 51 months (IQR, 10-166 months). The median number of therapies prior to fostamatinib initiation was 4 (IQR, 2-5), including eltrombopag (76.1%), romiplostim (57.2%) and intravenous immunoglobulins (IVIG) (44.2%). Fifty-eight patients (42.0%) had signs/symptoms of bleeding in the month prior to treatment initiation. 79.0% of patients responded to fostamatinib with 53.6% complete responses (platelet count > 100 x 109 /L). Eighty-three patients (60.1%) received fostamatinib monotherapy achieving a high response rate (85.4%). The proportion of time in response during the 27-month period examined was 83.3%. The median time to platelet response was 11 days (IQR, 7-21 days). Sixty-seven patients (48.5%) experienced adverse events, mainly grade 1-2, the commonest of which were diarrhea (n = 28) and hypertension (n = 21). One patient had deep venous thrombosis and one patient developed acute myocardial infarction. Fostamatinib was shown to be effective with good safety profile in patients with primary and secondary ITP across a wide age spectrum in this real-world study.

Y-chromosome in the olfactory neuroepithelium as a potential biomarker of depression in women with male offspring: an exploratory study.

The persistence of fetal cells in the mother (fetal microchimerism (FMc)) has been described in maternal tissues essential to the newborn. FMc is associated with several diseases that start or worsen in pregnancy or postpartum. This exploratory study reports-for the first time-the presence of FMc in the olfactory neuroepithelium (ON) of both healthy and depressed women with male offspring. However, depressed women had fewer microchimeric cells (digital PCR). The existence of FMc in the ON could facilitate mother-child bonding. These findings open new pathways to study FMc in the ON, female depression, and mother-child bonding.

Free skin micrografts with cyanoacrylate as outpatient treatment for venous leg ulcers.

OBJECTIVE: The present study describes an ambulatory, free skin micrograft technique with cyanoacrylate as a coadjuvant venous leg ulcer (VLU) healing strategy and its outcomes after one month. METHODS: This prospective study involved Comprehensive Classification System for Chronic Venous Disorders (CEAP) stage C6 patients with good granulation tissue and negative culture results, consecutively recruited in January 2017 in the Hospital Clinico San Carlos. A skin micrograft was harvested from the anterior surface of the patient's thigh with a 0.4cm punch (0.12cm2). The graft was adhered to the ulcer bed with cyanoacrylate. Anti-adherent dressing and double-layer bandaging was applied, with weekly replacements. Measurements were obtained of the surface of the VLU and graft progression (in cm2) using a photographic grid. RESULTS: A total of 12 VLUs in 12 patients were included, with a mean treated surface of 20.32±13.9cm2. A total of 18 grafts were placed and all were found to be viable after one week. Average graft growth was not noticeable after one week but was found to be 0.25±0.08cm2 after week two, 0.41±0.98cm2 after week three, and 0.70±0.15cm2 after week four (p<0.001). There were no complications in the donor zone. CONCLUSION: The findings of this study show that free skin micrografting with cyanoacrylate as outpatient treatment for VLUs was simple, rapid and without complication in this study, and may contribute to its wider application in clinical use.

Change in functioning outcomes as a predictor of the course of depression: a 12-month longitudinal study.

PURPOSE: Functioning is a necessary diagnostic criterion for depression, and thus routinely assessed in depressive patients. While it is highly informative of disorder severity, its change has not been tested for prognostic purposes. Our study aimed to analyze to what extent early functioning changes predict depression in the mid-term. METHODS: Longitudinal study (four occasions: baseline, 1, 3, and 12 months) of 243 patients with depressive symptomatology at three different services (primary care, outpatients, and hospital). Functioning was assessed on the first three occasions using the Global Assessment of Functioning (GAF), the WHODAS-2.0, and a self-reported functioning (SRF) rating scale. Growth mixture modeling of initial assessments served to estimate individual person-change parameters of each outcome. Person-growth parameters were used as predictors of major depressive episode at 12 months in a logistic regression model, adjusted by sex, age, healthcare level, and depression clinical status at third month. Predictive accuracy of all measures was assessed with area under the receiver operating curve (AUC). RESULTS: Of the 179 patients who completed all assessments, 58% had an active depression episode at baseline and 20% at 12 months (64% non-recoveries and 36% new onsets). Individual trends of change in functioning significantly predicted patient depression status a year later (AUCWHODAS = 0.76; AUCGAF = 0.92; AUCSRF = 0.93). CONCLUSIONS: Longitudinal modeling of functioning was highly predictive of patients' clinical status after 1 year. Although clinical and patient-reported assessment had high prognostic value, the use of very simple patient-reported outcome measures could improve case management outside specialized psychiatric services.

TGFß Superfamily Members as Regulators of B Cell Development and Function-Implications for Autoimmunity.

The TGFß superfamily is composed of more than 33 growth and differentiation factors, including TGFß1, ß2, ß3, BMPs, GDFs, nodal-related proteins, and activins. These members usually exert pleiotropic actions on several tissues and control multiple cellular processes, such as cell growth, cell survival, cell migration, cell fate specification, and differentiation, both during embryonic development and postnatal life. Although the effects of these factors on immune responses were elucidated long ago, most studies have been focused on the actions of TGFßs on T cells, as major regulators of adaptive immunity. In this review, we discuss new findings about the involvement of TGFß superfamily members in the control of B cell development and function. Moreover, the potential contribution of TGFß signaling to control B cell-mediated autoimmune diseases and its utility in the design of new therapies are also discussed.

Imiquimod Treatment Causes Systemic Disease in Mice Resembling Generalized Pustular Psoriasis in an IL-1 and IL-36 Dependent Manner.

Generalized pustular psoriasis (GPP) is a severe form of psoriasis that can be caused by missense mutations in the interleukin-36 (IL-36) receptor antagonist. In addition to neutrophil rich skin inflammation, GPP patients typically also experience anorexia, fever, malaise, and pain. The imiquimod-induced skin inflammation mouse model has rapidly become a popular way to study plaque psoriasis, which typically does not involve symptoms of systemic disease. In this model, neutrophil recruitment to the skin is dependent upon the inflammatory mediators IL-1, via its receptor IL-1R1, and IL-36α. Unexpectedly, we observed that mice also exhibited signs of anorexia (weight loss and decreased food intake), general malaise (decreased activity and loss of interest in building nests), and pain (nose bulging and hunched posture). A scoring system allowing quantitative comparisons of test groups was developed. Female mice were found to develop more severe disease than male mice. Furthermore, mice deficient in both IL-1R1 and IL-36α are nearly disease-free, while mice lacking only one of these inflammatory mediators have less severe disease than wild type mice. Hence, the imiquimod-induced skin inflammation mouse model recapitulates not only plaque psoriasis, but also the more severe symptoms, that is, anorexia, malaise, and pain, seen in GPP.

DETECTION OF ANXIETY DISORDERS IN PRIMARY CARE: A META-ANALYSIS OF ASSISTED AND UNASSISTED DIAGNOSES.

BACKGROUND: Evidence suggests that general practitioners (GPs) fail to diagnose up to half of common mental disorder cases. Yet no previous research has systematically summarized the evidence in the case of anxiety disorders. The aim of this review was to systematically assess and meta-analyze the diagnostic accuracy of GPs' assisted (i.e., using severity scales/diagnostic instruments) and unassisted (without such tools) diagnoses of anxiety disorders. METHODS: Systematic review (PROSPERO registry CRD42013006736) was conducted. Embase, Ovid Journals--Ovid SP Medline, Pubmed, PsycINFO, Scopus, Web of Science, and Science Direct were searched from January 1980 through June 2014. Seven investigators, working in pairs, evaluated studies for eligibility. The quality of included studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool version 2 (QUADAS-2). The main outcome measures were sensitivity and specificity of clinical diagnoses of any anxiety disorder. We pooled sensitivity and specificity levels from included studies using bivariate meta-analyses. RESULTS: Twenty-four studies were included in the meta-analysis with a total sample of 34,902 patients. Pooled sensitivity and specificity were estimated at 44.5% (95% CI 33.7-55.9%) and 90.8% (95% CI 87-93.5%). GPs' sensitivity was higher when diagnoses were assisted (63.6%, 95% CI 50.3-75.1%) than when unassisted (30.5%, 95% CI 20.7-42.5%) to the expense of some specificity loss (87.9%, 95% CI 81.3-92.4% vs. 91.4%, 95% CI 86.6-94.6%, respectively). Identification rates remained constant over time (P-value = .998). CONCLUSIONS: The use of diagnostic tools might improve detection of anxiety disorders in "primary care."

Validation of clinical symptom IRT scores for diagnosis and severity assessment of common mental disorders.

PURPOSE: We studied the validity and responsiveness of an item response theory (IRT) scoring method for assessing major depressive episode (MDE) and generalized anxiety disorder (GAD) severity based on direct assessment of DSM-IV-TR symptoms. METHODS: Prospective cohort study (baseline, 1-month, 3-months assessments) of patients seeking help for incident or aggravated mood or anxiety symptoms from primary, outpatient and inpatient mental health centers (N = 244; 67.81 % active cases - 100 % under psychiatric treatment). The drop-out rate at 3 months was 24.89 %. Patients were assessed at each follow-up for presence/absence of DSM-IV symptoms of MDE (nine symptoms) and GAD (eight symptoms). IRT scores for depression (INS-D) and anxiety (INS-G), based on response patterns, were obtained by means of a 2-parameter model. Diagnostic accuracy was assessed with receiver operating characteristic analysis, using a blinded MINI interview as gold standard. Scores' construct validity was compared with external clinician-administered (Hamilton Depression Rating Scale, HRSD; Hamilton Anxiety Rating Scale, HAM-A) and self-reported severity measures (PHQ-9; Beck Anxiety Inventory-Subjective Aspects, BAI-Sub). Responsiveness was analyzed based on the evolution of HRSD and HAM-A scores. RESULTS: Both severity scores showed excellent reliability (INS-D: 0.92; INS-G: 0.93) and yielded high diagnostic accuracy (INS-D: AUC = 0.96; INS-G: AUC = 0.91) with respect to MINI diagnoses. INS-D and INS-G had higher correlations with clinician-administered measures of the same disorder (INS-D-HRSD: 0.73; INS-G-HAM-A: 0.53) than with self-reported measures (INS-D-PHQ-9: 0.69; INS-G-BAI-Sub: 0.49). Patients who recovered during follow-up showed important decreases in severity (Cohen's d INS-D:-1.38; INS-G: -1.75). About 90 % variance of INS-D and INS-G score changes over time was associated with changes in clinical status. CONCLUSIONS: INS-D and INS-G are short reliable, valid, and responsive measures that can be used for diagnostic and severity assessment of mood and anxiety disorders in outpatient care.

Cornual adenomyosis in Essure® device users and in patients hysterectomized for other causes: A retrospective cohort study.

OBJECTIVE: To determine whether adenomyosis is present in the cornual portion of hysterectomies of symptomatic sterilization device users and in patients hysterectomized for different benign causes and who presented with pelvic pain and/or menstrual alterations. METHODS: An observational, analytical, cross-sectional, single-center, retrospective cohort study was conducted in a secondary level hospital. Cohort 1 consisted of women who had Essure® hysteroscopic sterilization devices inserted between 2009 and 2017, who developed gynecologic symptoms (pelvic pain, heavy menstrual bleeding, and/or abnormal uterine bleeding) and who underwent a hysterectomy for explantation of the devices. Cohort 2 consisted of women with the same gynecologic symptoms, who underwent a hysterectomy for other benign causes. All surgeries were performed by the gynecology team between 2018 and 2022. A descriptive and comparative analysis of sociodemographic, clinical characteristics, and pathologic findings between cohorts was made. RESULTS: In total, 96 patients were studied (cohort 1 included 34 women, cohort 2 included 62 women). Pelvic pain was found to be more frequent in the cohort of Essure users (76.47% vs. 50%, P = 0.012), with a ratio of three times higher in this group (odds ratio 3.25, 95% confidence interval 1.27-8.28). Adenomyosis was more frequently found in the Essure group, both at corporal and cornual portions, the latter being five times higher in this cohort (relative risk = 5.47; 95% confidence interval 1.17-25.64). CONCLUSIONS: The present study may be the first to describe cornual adenomyosis related to Essure devices. These devices may play a role in the development of adenomyosis and, consequently, pelvic pain. However, causality is difficult to establish.

Retrospective registry of patients with locally advanced/metastatic HR+/HER2- breast cancer treated in clinical practice in Andalusia.

BACKGROUND: Limited data are available regarding the real-world effectiveness and safety of Cyclin Dependent Kinase 4/6 inhibitor (CDK4/6i) (palbociclib/ribociclib) just as a first-line treatment for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR + /HER2‒) metastatic breast cancer (MBC). OBJECTIVE: To assess whether clinical or demographic characteristics limit access to first-line CDK4/6i treatment in clinical practice in the Autonomous Community of Andalusia (Spain) between November 2017 and April 2020. In addition, effectiveness will be described in an exploratory analysis. METHODS: Physicians from 12 centers participated in selecting demographic and clinical characteristics, treatment, and outcome data from women with HR + /HER2- MBC treated with or without CDK4/6i in addition to hormonal in the first-line setting, in a 3:1 proportion. Kaplan-Meier analysis estimated progression-free rates (PFRs) and survival rates (SRs). RESULTS: A total of 212 patients were included, of whom 175 (82.5%) were in the CDK4/6i treatment group and 37 (17.5%) were in the non-CDK4/6i treatment group (control group). Patients in the CDK 4/6i treatment group were younger (p = 0.0011), the biopsies of the metastatic site at the moment of the relapse were most commonly performed (p = 0.0454), and had multiple metastatic sites (p = 0.0025). The clinical benefit rate (CBR) was 82.3% in the CDK4/6i group and 67.8% in the control group. Median time to a progression event or death (PFS) was 20.4 months (95%CI 15.6-28) in the CDK4/6i group and 12.1 months (95%CI 7.9-not reached) in the control group. CONCLUSIONS: Younger patients, biopsies of metastatic disease and with multiple metastatic sites were more frequently treated with CDK4/6i in our daily clinical practice.

Real-world experience with pertuzumab and trastuzumab combined with chemotherapy in neoadjuvant treatment for patients with early-stage HER2-positive breast cancer: the NEOPERSUR study.

PURPOSE: HER2-targeted therapies have dramatically improved outcomes of patients with HER2-positive breast cancer (BC), as demonstrated in neoadjuvant trials. This study aims to provide real-world evidence on the use and effectiveness of combined pertuzumab, trastuzumab and chemotherapy (CT) in early-stage HER2-positive BC. METHODS: A retrospective, multicentre study was conducted on patients diagnosed with HER2-positive early BC treated with neoadjuvant pertuzumab and trastuzumab plus CT at 13 Spanish sites. The primary endpoint was pathological complete response (pCR). RESULTS: A total of 310 patients were included. Pertuzumab and trastuzumab were combined with anthracyclines and taxanes, carboplatin and docetaxel, and taxane-based CT in 77.1%, 16.5%, and 6.5% of patients, respectively. Overall, the pCR rate was 62.2%. The pCR was higher amongst patients with hormone receptor-negative tumours and with tumours expressing higher levels of Ki-67 (> 20%). After postoperative adjuvant treatment, 13.9% of patients relapsed. Those patients who did not achieve pCR, with tumours at advanced stages (III), and with node-positive disease were more likely to experience distant relapse. Median overall survival (OS) and distant disease-free survival (D-DFS) were not reached at the study end. The estimated mean OS and D-DFS times were 7.5 (95% CI 7.3-7.7) and 7.3 (95% CI 7.1-7.5) years, respectively (both were significantly longer amongst patients who achieved pCR). Grade 3-4 anti-HER2 related toxicities were reported in six (1.9%) patients. CONCLUSION: Neoadjuvant pertuzumab and trastuzumab plus CT achieve high pCR rates in real-life patients with HER2-positive early BC, showing an acceptable safety profile. Innovative adjuvant strategies are essential in patients at high risk of distant disease recurrence.

Analysis of psychometric questionnaires used in patient selection for bariatric surgery.

INTRODUCTION: In severe forms of obesity there is a high prevalence of psychopathological comorbidity. Psychiatric evaluation is an important component of comprehensive obesity care and contributes to optimizing therapeutic results after bariatric surgery. OBJECTIVE: To assess the effectiveness of psychometric tests used in the protocol for selecting patients for bariatric surgery. MATERIAL AND METHODS: Retrospective naturalistic observational study of 100 patients who were candidates for bariatric surgery. Patients who complete the psychometric protocol and the psychiatric interview between January 2019 and June 2021 are included. Two groups are formed: those considered unfit for any psychopathological reason and those considered fit. To evaluate the effectiveness of the tests used, ROC curves will be used. The sensitivity and specificity values of each test used will be obtained. RESULTS: 97 patients included, aged between 20 and 61 years, 64.9% women. 51.5% had a family history and 38.1% a personal history of any psychiatric disorder. Regarding the area under the curve, the scales that presented a value greater than 0.7 were the YFAS total score (0.771), HADS-D (0.757), the Edinburgh Bulimia total score (0.747), the severity score of YFAS (0.722) and Edinburgh Bulimia Severity Score (0.705). The most frequent diagnoses as a cause of exclusion were Food Addiction 8 (20.5%) and Generalized Anxiety Disorder (GAD) 6 (15.5%). CONCLUSIONS: The YFAS, BITE and HADS-A scales were useful to discriminate those patients considered unsuitable for bariatric surgery for any psychopathological cause.

Telemedicine screening program for diabetic retinopathy in patients with type 1 diabetes mellitus.

PURPOSE: To analyze the results of the telemedicine screening program for diabetic retinopathy (DR) in patients with type 1 diabetes conducted by the Endocrinology and Nutrition Management Unit of Virgen del Rocío University Hospital. METHODS: This cross-sectional study comprised patients with type 1 diabetes mellitus (DM) in our DR screening program from January 2018 to November 2020. Fundus photographs are performed by trained nurses and reviewed by a trained endocrinologist. Those suggestive of pathology are sent to ophthalmology through a telematic program for review. RESULTS: Of the 995 fundus photographs evaluated, 646 (65.3%) showed no evidence of DR, 327 (33.1%) presented possible DR, and 16 (1.6%) were not gradable. The diagnosis was confirmed in 254 patients after reviewing by ophthalmology, and the screening program achieved a positive predictive value for DR of 77.7%. Seventy-three were excluded by ophthalmology due to the absence of DR (false positive rate - 22.3%). In 92.5% of the cases classified by the ophthalmologist, the degree of DR was mild or very mild. CONCLUSION: Our telemedicine screening program for DR in patients with type 1 DM is consistent with the literature. Effective screening for DR is performed, with patients diagnosed in the early stages. Telemedicine programs facilitate efficient communication among healthcare personnel.

Importance of immunometabolic markers for the classification of patients with major depressive disorder using machine learning.

BACKGROUND: Although there is scientific evidence of the presence of immunometabolic alterations in major depression, not all patients present them. Recent studies point to the association between an inflammatory phenotype and certain clinical symptoms in patients with depression. The objective of our study was to classify major depression disorder patients using supervised learning algorithms or machine learning, based on immunometabolic and oxidative stress biomarkers and lifestyle habits. METHODS: Taking into account a series of inflammatory and oxidative stress biomarkers (C-reactive protein (CRP), tumor necrosis factor (TNF), 4-hydroxynonenal (HNE) and glutathione), metabolic risk markers (blood pressure, waist circumference and glucose, triglyceride and cholesterol levels) and lifestyle habits of the participants (physical activity, smoking and alcohol consumption), a study was carried out using machine learning in a sample of 171 participants, 91 patients with depression (71.42% women, mean age = 50.64) and 80 healthy subjects (67.50% women, mean age = 49.12). The algorithm used was the support vector machine, performing cross validation, by which the subdivision of the sample in training (70%) and test (30%) was carried out in order to estimate the precision of the model. The prediction of belonging to the patient group (MDD patients versus control subjects), melancholic type (melancholic versus non-melancholic patients) or resistant depression group (treatment-resistant versus non-treatment-resistant) was based on the importance of each of the immunometabolic and lifestyle variables. RESULTS: With the application of the algorithm, controls versus patients, such as patients with melancholic symptoms versus non-melancholic symptoms, and resistant versus non-resistant symptoms in the test phase were optimally classified. The variables that showed greater importance, according to the results of the area under the ROC curve, for the discrimination between healthy subjects and patients with depression were current alcohol consumption (AUC = 0.62), TNF-α levels (AUC = 0.61), glutathione redox status (AUC = 0.60) and the performance of both moderate (AUC = 0.59) and vigorous physical exercise (AUC = 0.58). On the other hand, the most important variables for classifying melancholic patients in relation to lifestyle habits were past (AUC = 0.65) and current (AUC = 0.60) tobacco habit, as well as walking routinely (AUC = 0.59) and in relation to immunometabolic markers were the levels of CRP (AUC = 0.62) and glucose (AUC = 0.58). In the analysis of the importance of the variables for the classification of treatment-resistant patients versus non-resistant patients, the systolic blood pressure (SBP) variable was shown to be the most relevant (AUC = 0.67). Other immunometabolic variables were also among the most important such as TNF-α (AUC = 0.65) and waist circumference (AUC = 0.64). In this case, sex (AUC = 0.59) was also relevant along with alcohol (AUC = 0.58) and tobacco (AUC = 0.56) consumption. CONCLUSIONS: The results obtained in our study show that it is possible to predict the diagnosis of depression and its clinical typology from immunometabolic markers and lifestyle habits, using machine learning techniques. The use of this type of methodology could facilitate the identification of patients at risk of presenting depression and could be very useful for managing clinical heterogeneity.

Analysis of clinical data associated with Essure® sterilization devices: An expanded case series.

OBJECTIVES: To evaluate clinical data in women who underwent Essure® hysteroscopic sterilization and to determine whether this sterilization technique plays a role in developing new-onset symptoms. STUDY DESIGN: An observational, retrospective, single-center study. It was conducted in a secondary level hospital. It included 804 women who had Essure® hysteroscopic sterilization from 2009 to 2017. Charts from these women were reviewed from June 2009 to November 2019, searching for the development of gynecological symptoms (pelvic pain and bleeding disorders) and non-gynecological symptoms (bloating, joint pain, fatigue, headache, alopecia, allergy and depression). The sample was divided into two groups depending on whether they had developed gynecological symptoms (symptomatic group) or not (asymptomatic group), and a descriptive and comparative analysis was made between them. The impact of the global social alarm in 2015 regarding adverse events attributed to the devices, the development of non-gynecological symptoms, and the treatments required, including conservative and surgical options, were also described. RESULTS: Out of 804 women who had Essure® devices placed, 541(67.29%) remained asymptomatic, 263(32.71%) developed gynecological symptoms, and 41 of these (15.5% of the total sample) requested Essure® surgical removal. Pelvic pain was the most frequent symptom and the main reason for surgical removal. Bleeding alterations were the second most frequent symptom. Up to 55.89% described the symptoms after the social alarm. Non-gynecological symptoms were statistically significantly more frequent in the symptomatic group. CONCLUSIONS: More than a half of the women who underwent Essure® sterilization remained asymptomatic. The new-onset symptoms attributed to the devices are the minority and causality is difficult to establish. IMPLICATIONS STATEMENT: Our research provides new follow-up data about Essure® hysteroscopic sterilization. Association between gynecological symptoms and Essure® devices is difficult to demonstrate and some confounding factors may be implicated. The results we described, may guide and counsel medical-patient decisions for the treatment of symptoms related to the devices, including surgical removal.

Relationship between immunometabolic status and cognitive performance among major depression disorder patients.

BACKGROUND: Alterations in cognitive performance have been described in patients with major depressive disorder (MDD). However, the specific risk factors of these changes are not yet known. This study aimed to explore whether inmunometabolic parameters are related to cognitive performance in MDD in comparison to healthy controls (HC) METHODS: Sample consisted of 84 MDD patients and 78 HC. Both groups were compared on the results of cognitive performance measured with the Cambridge Neuropsychological Test Automated Battery (CANTAB), the presence of metabolic syndrome (MetS) and an inflammatory/oxidative index calculated by a principal component analysis of peripheral biomarkers (tumor necrosis factor, C-reactive protein and 4-hydroxynonenal). A multiple linear regression was carried out, to study the relationship between inmunometabolic variables and the global cognitive performance, being the latter the dependent variable. RESULTS: Significant differences were obtained in the inflammatory/oxidative index between both groups (F(1157)= 12.93; p < .001), also in cognitive performance (F(1157)= 56.75; p < .001). The inmunometabolic covariate regression model (i.e., condition (HC/MDD), sex, age and medication loading, MetS, inflammatory/oxidative index and the interaction between MetS and inflammatory/oxidative index) was statistically significant (F(7157)= 11.24; p < .01) and explained 31% of variance. The condition, being either MDD or HD, (B=-0.97; p < .001), age (B=-0.28; p < .001) and the interaction between inflammatory/oxidative index and MetS (B=-0.38; p = .02) were factors associated to cognitive performance. LIMITATIONS: Sample size was relatively small. The cross-sectional design of the study limits the possibilities of analysis. CONCLUSIONS: Our results provide evidence on the conjoint influence of metabolic and inflammatory dysregulation on cognitive dysfunction in MDD patients. In this way, our study opens a line of research in immunometabolic agents to deal with cognitive decline associated with MDD.

Early- and late-onset depression in the older: no differences found within the melancholic subtype.

OBJECTIVE: Several studies have reported clinical and biological differences between early- and late-onset(EO and LO) depression, which suggest different underlying aetiological processes. The aim of the present study is to examine whether there are differences between EO and LO depressed patients with melancholy, controlling for current age, with regard to clinical variables, vascular risk factors and family history of affective disorders or suicide. METHODS: One hundred and twenty-one melancholic patients were divided into three groups: patients with current age and onset earlier than 60 (N = 60), patients aged 60 or over and with onset at 60 or later(N = 30) and patients aged 60 or over and with onset before the age of 60 (N = 31). Systematic clinical data were collected with the structured interview 'The Schedule for Affective Disorders and Schizophrenia'. Symptom ratings at admission and at discharge were assessed by means of the 21-item Hamilton Depression Rating Scale, the Hamilton Anxiety Scale and the Widlöcher Depression Retardation Scale. Family history of affective disorders or suicide was obtained using the Family History Research Diagnostic Criteria. Vascular risk factors were also recorded. RESULTS: The only symptoms that differed across the groups were feelings of anger and irritability, which scored lower in the LO older group. No other significant differences were found in the variables studied. CONCLUSION: According to this study, LO depression with melancholia should not be considered as a distinct entity. Further studies on EO and LO-depression should consider this diagnostic subtype, among others, as a key variable.