Impact of Inherited Thrombophilia in Women with Obstetric Antiphospholipid Syndrome: A Single-Center Study and Literature Review.

Inherited thrombophilia (IT) has been implicated as a potential causal factor of adverse pregnancy outcomes (APOs), including recurrent miscarriage with and without the presence of antiphospholipid syndrome (APS). The aim of this study was to assess the prevalence and impact of IT on fetal-maternal outcomes and thrombotic risk in women within the spectrum of obstetric APS. Three hundred and twenty-eight women with APS-related obstetric morbidity ever pregnant were included. Of these, 74 met the APS classification criteria, 169 were non-criteria (NC)-APS, and 85 were seronegative (SN)-APS. Patients with other autoimmune diseases were excluded. APOs included early pregnancy loss, fetal death, preeclampsia, abruptio placentae, and preterm birth. Successful pregnancy was defined as the achievement of a live newborn. A literature search was also performed. The mean age of the overall group was 33.9 ± 5.3 years, and the patients were followed up for 35 (11-79) months. During the study period, there were 1332 pregnancies. Nearly 14% of the patients had an associated IT. IT patients more frequently received the standard-of-care (SoC) therapy. The presence of IT was not associated with worse maternal-fetal outcomes in patients treated with SoC treatment. Overall, IT patients had a lower frequency of newborns without treatment, especially those without definite APS. In addition, IT did not increase the risk of thrombosis during pregnancy or the postpartum period. A detailed analysis of the literature review identified only four publications related to our study and did not show conclusive evidence of the impact of IT on patients with obstetric APS. The group of women with APS-related obstetric morbidity and IT who did not receive treatment, especially those without definite APS, had a worse prognosis in terms of a live birth. However, with SoC therapy, the prognosis is similar in those patients without IT. The association of IT with APS does not seem to predispose to the development of thrombosis during pregnancy and/or the postpartum period.

Bone formation by human paediatric marrow stromal cells in a functional allogeneic immune system.

Allogeneic stem-cell based regenerative medicine is a promising approach for bone defect repair. The use of chondrogenically differentiated human marrow stromal cells (MSCs) has been shown to lead to bone formation by endochondral ossification in immunodeficient pre-clinical models. However, an insight into the interactions between the allogeneic immune system and the human MSC-derived bone grafts has not been fully achieved yet. The choice of a potent source of MSCs isolated from pediatric donors with consistent differentiation and high proliferation abilities, as well as low immunogenicity, could increase the chance of success for bone allografts. In this study, we employed an immunodeficient animal model humanised with allogeneic immune cells to study the immune responses towards chondrogenically differentiated human pediatric MSCs (ch-pMSCs). We show that ch-differentiated pMSCs remained non-immunogenic to allogeneic CD4 and CD8 T cells in an in vitro co-culture model. After subcutaneous implantation in mice, ch-pMSC-derived grafts were able to initiate bone mineralisation in the presence of an allogeneic immune system for 3 weeks without the onset of immune responses. Re-exposing the splenocytes of the humanised animals to pMSCs did not trigger further T cell proliferation, suggesting an absence of secondary immune responses. Moreover, ch-pMSCs generated mature bone after 8 weeks of implantation that persisted for up to 6 more weeks in the presence of an allogeneic immune system. These data collectively show that human allogeneic chondrogenically differentiated pediatric MSCs might be a safe and potent option for bone defect repair in the tissue engineering and regenerative medicine setting.

Impact of homeostatic body hydration status, evaluated by hemodynamic measures, on different pain sensitization paths to a chronic pain syndrome.

Contrasting findings on the mechanisms of chronic pain and hypertension development render the current conventional evidence of a negative relationship between blood pressure (BP) and pain severity insufficient for developing personalized treatments. In this interdisciplinary study, patients with fibromyalgia (FM) exhibiting clinically normal or elevated BP, alongside healthy participants were assessed. Different pain sensitization responses were evaluated using a dynamic 'slowly repeated evoked pain' (SREP) measure, as well as static pain pressure threshold and tolerance measures. Cardiovascular responses to clino-orthostatic (lying-standing) challenges were also examined as acute re- and de-hydration events, challenging cardiovascular and cerebrovascular homeostasis. These challenges involve compensating effects from various cardiac preload or afterload mechanisms associated with different homeostatic body hydration statuses. Additionally, hair cortisol concentration was considered as a factor with an impact on chronic hydration statuses. Pain windup (SREP) and lower pain threshold in FM patients were found to be related to BP rise during clinostatic (lying) rehydration or orthostatic (standing) dehydration events, respectively. These events were determined by acute systemic vasoconstriction (i.e., cardiac afterload response) overcompensating for clinostatic or orthostatic cardiac preload under-responses (low cardiac output or stroke volume). Lower pain tolerance was associated with tonic blood pressure reduction, determined by permanent hypovolemia (low stroke volume) decompensated by permanent systemic vasodilation. In conclusion, the body hydration status profiles assessed by (re)activity of systemic vascular resistance and effective blood volume-related measures can help predict the risk and intensity of different pain sensitization components in chronic pain syndrome, facilitating a more personalized management approach.

Prognostic effect of systematic geriatric assessment on patients with acute heart failure.

AIMS: Frailty and dependence are frequent in patients admitted for acute heart failure (AHF), but their prognostic significance is unknown, especially in young adults. We aimed to study in adults admitted for AHF, regardless of age, the effect of frailty and dependence on the incidence of mortality and a combined event of mortality, readmissions for AHF, and visits to the emergency room (ER) for AHF at 1 and 6 months. METHODS AND RESULTS: We designed a prospective cohort study by including all the patients with AHF admitted in our Cardiology Department from July 2020 through May 2021. A multidimensional geriatric assessment was performed during the admission. We clinically followed up the patients 6 months after discharge. We enrolled 202 patients. The mean age was 73 ± 12.32 years, and 100 (49.5%) of the patients were elderly (>75 years). Just 78 patients (38.6%) were women, and 100 (49.5%) had previous HF. Frailty (FRAIL ≥ 3) was observed in 68 (33.7%) patients (mean FRAIL score: 1.88 ± 1.48). Dependence (Barthel < 100) was observed in 65 (32.2%) patients (mean Barthel index: 94.38 ± 11.21). Frailty and dependence showed a significant association with both prognostic events at 1 and 6 months. In the multivariable analysis, frailty was associated with higher mortality at 1 month [hazard ratio (HR) 12.61, 95% confidence interval (CI) 1.57-101.47, P = 0.017] but not at 6 months (HR 2.25, 95% CI 0.61-8.26, P = 0.224) or with the combined endpoint at neither 1 month (HR 1.64, 95% CI 0.54-5.03, P = 0.384) nor 6 months (HR 1.35, 95% CI 0.75-2.46, P = 0.320). Dependence was related to higher mortality at 1 month (HR 13.04, 95% CI 1.62-104.75, P = 0.016) and 6 months (HR 7.18, 95% CI 1.99-25.86, P = 0.003) and to higher incidence of the combined event at 1 month (HR 5.93, 95% CI 1.63-21.50, P = 0.007) and 6 months (HR 2.62, 95% CI 1.49-4.61, P = 0.001). CONCLUSIONS: In AHF patients, frailty and dependence implied a worse prognosis, rising mortality, readmissions, and ER visits for AHF.

Comparative study of the glistening between four intraocular lens models assessed by OCT and deep learning.

PURPOSE: To evaluate the glistening in 4 different models of intraocular lenses (IOLs) using optical coherence tomography (OCT) and deep learning (DL). SETTING: Centro Internacional de Oftalmología Avanzada (Madrid, Spain). DESIGN: Cross-sectional study. METHODS: 325 eyes were assessed for the presence and severity of glistening in 4 IOL models: ReSTOR+3 SN6AD1 (n = 41), SN60WF (n = 110), PanOptix TFNT (n = 128) and Vivity DFT015 (n = 46). The presence of glistening was analyzed using OCT, identifying the presence of hyperreflective foci (HRF) in the central area of the IOL. A manual and an original DL-based quantification algorithm designed for this purpose was applied. RESULTS: Glistening was detected in 22 (53.7%) ReSTOR SN6AD1, 44 (40%) SN60WF, 49 (38.3%) PanOptix TFNT, and 4 (8.7%) Vivity DFT015 IOLs, when any grade was considered. In the comparison of the different types of IOLs, global glistening measured as total HRF was 17.3 ± 25.9 for the ReSTOR+3; 9.3 ± 15.7 for the SN60WF; 6.9 ± 10.5 for the PanOptix; and 1.2 ± 2.6 for the Vivity ( P < .05). There was excellent agreement between manual and DL-based quantification (≥0.829). CONCLUSIONS: It is possible to quantify, classify and compare the glistening severity in different IOL models using OCT images in a simple and objective manner with a DL algorithm. In the comparative study, the Vivity presented the lowest severity of glistening.

Cross-cultural adaptation of the FRAIL scale for critically ill patients in Spain.

AIM: To translate and culturally adapt the FRAIL scale into Spanish and perform a preliminary test of diagnostic accuracy in patients admitted to intensive care units. DESIGN: Cross-sectional diagnostic study. METHODS: Five intensive care units (ICU) in Spain were participated. Stage 1: Three native Spanish-speaking bilingual translators familiar with the field of critical care translated the scale from English into Spanish. Stage 2: Three native English-speaking bilingual translators familiar with critical care medicine. Stage 3: Authors of the original scale compared the English original and back-translated versions of the scale. Stage 4: Five nurses with more than 5 years of ICU experience and five critical care physicians assessed the comprehension and relevance of each of the items of the Spanish version in 30 patients of 3 different age ranges (<50, 50-65 and >65 years). RESULTS: The FRAIL scale was translated and adapted cross-culturally for patients admitted to intensive care units in Spain. The process consisted of four stages: translation, back translation, comparison and pilot test. There was good correspondence between the original scale and the Spanish version in 100% of the items. The participating patients assessed the relevance (content validity) and comprehensibility (face validity) of each of the items of the first Spanish version. The relevance of some of the items scored low when the scale was used in patients younger than 65 years. CONCLUSIONS: We have cross-culturally adapted the FRAIL scale, originally in English, to Spanish for its use in the critical care medical setting in Spanish-speaking countries. IMPLICATIONS FOR PROFESSIONALS: Physicians and nurses can apply the new scale to all patients admitted to the intensive care units. Nursing care can be adapted according to frailty, trying to reduce the side effects of admission to these units for the most fragile patients. REPORTING METHOD: The manuscript's authors have adhered to the EQUATOR guidelines, using the COSMIN reporting guideline for studies on the measurement properties of patient-reported outcome measures. PATIENT OR PUBLIC CONTRIBUTION: In a pilot clinical study, we applied the first version of the FRAIL-Spain scale to intensive care unit (ICU) patients. Five nurses with more than 5 years of ICU experience and five critical care physicians assessed the relevance (content validity) and comprehensibility (face validity) of the five items of the first Spanish version. Relevance was assessed using a 4-point Likert scale ranging from 1 (no relevance) to 4 (high relevance), and comprehensibility was assessed as poor, acceptable or good. Each health professional applied the scale to three patients (total number of patients = 30) of three different age ranges (<50, 50-65 and >65 years) and recorded the time of application of the scale to each patient. Although the frailty scales were initially created by geriatricians to be applied to the elders, there is little experience with their application in critically ill patients of any age. Therefore, more information is needed to determine the relevance of using this scale in critical care patients. In this pilot study, we considered that nurses and critical care physicians should evaluate frailty using this adapted scale in adult patients admitted to the Intensive Care Units.

Normative Topographic Anterior and Posterior Corneal Astigmatism: Axis Distribution and Its Relations with Ocular and Biometric Parameters.

Corneal astigmatism correction is a key factor when planning refractive treatment for ametropies with intraocular lenses. We aim to obtain normative anterior and posterior corneal astigmatism (ACA and PCA, respectively) data in a local population and to describe their axis distribution and their association with other parameters. A total of 795 patients with no ocular diseases were evaluated with corneal tomography and optical biometry. Only data of the right eye were included. Mean ACA and PCA were 1.01 ± 0.79 and 0.34 ± 0.17 D, respectively. Vertical steep axis distribution was 73.5% for ACA and 93.3% for PCA. Axis orientation between ACA and PCA matched best for vertical orientation (especially 90° to 120°). Vertical ACA orientation frequency decreased with age, with a more positive sphere and less ACA. Vertical PCA orientation frequency increased with higher PCA. Eyes with vertical ACA orientation were younger and showed a greater white-to-white (WTW) measurement, anterior corneal elevations, ACA and PCA. Eyes with vertical PCA orientation were younger and showed greater anterior corneal elevations and PCA. Normative ACA and PCA data in a Spanish population were presented. Steep axis orientations presented differences with age, WTW, anterior corneal elevations and astigmatism.

Reply to Stanojcic et al. Comment on "Fernández-Vigo et al. Objective Classification of Glistening in Implanted Intraocular Lenses Using Optical Coherence Tomography: Proposal for a New Classification and Grading System. J. Clin. Med. 2023, 12, 2351".

We appreciate the comments made by Stanojcic et al. [...].

Objective Classification of Glistening in Implanted Intraocular Lenses Using Optical Coherence Tomography: Proposal for a New Classification and Grading System.

PURPOSE: To propose a classification of the glistening in intraocular lenses (IOL) using swept-source optical coherence tomography (SS-OCT) by means of a simple, objective and reproducible method that allows the quantification of the presence and severity of glistening. METHODS: A cross-sectional study on a sample of 150 eyes of 150 patients who underwent cataract surgery in at least 600 days before the exam and attended a routine examination. Each subject was examined by SS-OCT after pupil dilation, identifying the presence of glistening or hyperreflective foci (HRF) in the central area of the IOL. The degree of glistening was classified into four categories: 0: ≤5 HRF; 1: 6 to 15 HRF; 2: 16 to 30 HRF; and 3: >30 HRF. The intra and interobserver reproducibility (intraclass correlation coefficient, ICC) in the quantification and classification of the glistening were calculated. The correlation between the horizontal and vertical scan of the IOL was also assessed. RESULTS: Glistening was present in the IOL in 42.7% of the patients. The mean number of HRF or glistening microvacuoles was 10.4 ± 26.2 (range 0 to 239). In total, 63.3% of the IOLs had a grade 0, 20% grade a 1, 6.7% grade a 2 and 10% a grade 3. The intraobserver and interobserver reproducibility were very high, both for the absolute quantification of the glistening (ICC ≥ 0.994) and for the severity scale (ICC ≥ 0.967). There was an excellent correlation in the quantification of the IOL glistening between the horizontal and vertical scans (R ≥ 0.834; p < 0.001). CONCLUSIONS: The use of SS-OCT makes it possible to identify, quantify and classify IOL glistening in a simple, objective and reproducible way. This technique could provide relevant information for the study of the glistening on IOLs.

Fast systematic geriatric assessment in acute heart failure patients admitted in Cardiology.

BACKGROUND: Heart failure prevalence is increasing in elder adults. These patients usually present geriatric syndromes, especially frailty. The effect of frailty on heart failure is under discussion but there are few data about the clinical characterization of frail patients who are admitted for acute heart failure decompensation. OBJECTIVE: The purpose of this study was to study the differences in clinical baseline variables and geriatric scales between frail and non-frail patients admitted to the Cardiology unit via the Emergency Department for acute heart failure. METHODS: We enrolled all patients with acute heart failure who were admitted to the Cardiology unit from the Emergency Department of our hospital from July 2020 through May 2021. A multidimensional and comprehensive geriatric assessment was performed at the moment of admission. We studied differences in baseline variables and geriatric scales according to the frailty status determined by the FRAIL scale. RESULTS: A total of 202 patients were included. In the whole population, 68 (33.7%) patients presented frailty defined by a FRAIL score ≥ 3. The frail patients were older (80±9 vs. 69±12 years; p<0.001), and had a worse quality of life (58.31±12.18 vs.39.26±13.71 points; p<0.001) according to the Minnesota scale, presented high comorbidity (47 (69.1%) vs. 67 (50.4%) patients; p = 0.011) defined as ≥3 points according to the Charlson scale and were more dependent (40 (58.8%) vs. 25 (18.8%) patients; p<0.001) according to the Barthel scale. The frail patients presented higher MAGGIC risk scores (24.09±4.99 vs. 18.89±6.26; p<0.001). Despite this adverse profile, the treatments prescribed during the admission and at the hospital discharge were similar. CONCLUSIONS: The prevalence of geriatric syndromes, especially frailty, is very high in patients admitted for acute heart failure. Frail patients with acute heart failure had an adverse clinical profile with more prevalence of concomitant geriatric syndromes. Therefore, we consider that a geriatric assessment should be performed during the admission of acute heart failure patients to improve care and attention.

Green Synthesis, Characterization, and Empirical Thermal Conductivity Assessment of ZnO Nanofluids for High-Efficiency Heat-Transfer Applications.

ZnO nanoparticles were synthesized using lemon juice and zinc nitrate (1:1) through the green method. The structure of the biosynthesized ZnO nanoparticles was analyzed by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). The morphology and the size of ZnO nanoparticles were elucidated by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The powder was highly dispersed and irregularly shaped and the size of the nanoparticles ranged from 28 to 270 nm, depending on the shape of the particles. Thermal conductivity of the biosynthesized ZnO PG/W mixture 40:60 (v/v) nanofluids was measured within the temperature range of 20-70 °C. Experimental results revealed a linear increase in thermal conductivity with the rise of temperature and volume fraction. The enhancement of this parameter with temperature was probably due to the different shapes of the former agglomerates. They were broken by the thermal energy in aggregates of different forms. A correlation of these structures with temperature was established. Finally, an empirical model was developed for predicting thermal conductivity with particle volume fraction and temperature.

Specific facial emotion recognition deficits across the course of psychosis: A comparison of individuals with low-risk, high-risk, first-episode psychosis and multi-episode schizophrenia-spectrum disorders.

Our study aimed to explore the recognition of specific emotions across the course of psychosis. A visual task representing the six basic emotions was used to assess facial emotion recognition (FER) in 204 healthy controls classified into 152 low-risk (LR) and 52 high-risk for psychosis (HR), following a psychometric risk approach; and 100 patients: 44 with first-episode psychosis (FEP) and 56 with multi-episode schizophrenia-spectrum disorders (MES). First, we performed a MANCOVA to compare the four conditions. Next, we conducted a logistic regression to explore whether specific FER deficits predicted the presence of psychosis. Finally, we investigated the relationships of FER with psychosis-like experiences (PLEs) and psychotic symptoms. Global FER, anger and fear recognition were impaired in HR, FEP and MES. No differences between HR and FEP appeared. Moreover, fear and anger correctly classified 83% of individuals into LR or psychosis. FER was associated with PLEs and psychotic symptoms. Concluding, FER is early impaired in HR individuals and increases along the psychosis continuum. However, fear recognition is similarly impaired throughout the illness, suggesting a possible vulnerability marker. Furthermore, deficits in anger and fear recognition predicted the presence of psychosis. Therefore, we suggest that FER may be essential in detecting psychosis risk.

Utility of Genetic Testing in Patients with Transthyretin Amyloid Cardiomyopathy: A Brief Review.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly diagnosed condition. Although wild-type transthyretin amyloidosis (ATTRwt) is the most common ATTR-CM, hereditary transthyretin amyloidosis (ATTRv) may also occur. Currently, genetic testing for transthyretin pathogenic variants is recommended for patients with a confirmed clinical diagnosis of ATTR-CM. In fact, confirmation of this autosomal dominant pathogenic variant prompts genetic counselling and allows early identification of affected relatives. Additionally, in the presence of an ATTR-CM-associated polyneuropathy, specific drugs targeting transthyretin can be used. In this paper, we review the utility of genetic testing for the detection of pathogenic variants among patients harboring ATTR-CM and its impact on the natural history of the disease.

Non-Criteria Obstetric Antiphospholipid Syndrome: How Different Is from Sidney Criteria? A Single-Center Study.

This study aims to compare the demographic characteristics, clinical features, serology, and fetal-maternal outcomes between women with obstetric antiphospholipid syndrome (APS) and those with non-criteria (NC)-APS and seronegative (SN)-APS. Two-hundred and sixty-three women with APS obstetric morbidity ever pregnant were included. Of those, 66 met the APS classification criteria, 140 were NC-APS, and 57 were SN-APS. Patients with other autoimmune diseases were excluded. Adverse pregnancy outcomes (APO) included early pregnancy loss, fetal death, preeclampsia, abruptio placentae, and preterm birth. The mean age of the study group was 33.6 ± 5.3 years, and patients were followed up for 129.5 ± 81.9 months. In the NC-APS group, 31 (22.1%) did not fulfill clinical and serological criteria (Subgroup A), 49 (35%) did meet clinical but not serologic criteria (Subgroup B), and 60 (42.9%) fulfilled the serologic criteria but not the clinical ones (Subgroup C). The cardiovascular risk burden was higher in the APS group, due to a higher proportion of smoking. Patients with criteria APS received more intensive treatment than patients in the other study groups. The addition of standard of care (SoC) treatment significantly improved live birth and decreased APO in all groups. Significant clinical differences were observed between the study groups. However, when treated with SoC, fetal-maternal outcomes were similar, with a significant improvement in live births and a decrease in APO. Risk stratification in patients with obstetric morbidity associated with APS can help individualize their treatment.

Self-reported cognitive biases in psychosis: Validation of the Davos Assessment of Cognitive Biases Scale (DACOBS) in a Spanish sample of psychotic patients and healthy controls.

Cognitive biases have been demonstrated to be important in developing and maintaining psychosis. However, self-report measures for everyday clinical practice have been developed only recently. We aimed to study one of these instruments for assessing cognitive biases: the Davos Assessment of Cognitive Biases Scale (DACOBS). In a Spanish sample of 84 patients diagnosed with schizophrenia-spectrum disorders and 152 healthy controls, we examined a) the factor structure using Confirmatory Factor Analysis (CFA) to test the original one-, three- and seven-factor solutions, b) the reliability (Cronbach's alpha), c) the discriminative power (Multivariate Analysis of Covariance - MANCOVA) and d) the relationships of cognitive biases with positive psychotic-like experiences (PPLEs) in healthy individuals and with psychotic symptoms in schizophrenia-spectrum patients. The CFA revealed that the seven-factor solution achieved the best fit. The DACOBS overall scale (Cronbach's alpha = .92) and subscales obtained good internal consistencies. MANCOVA, controlling for age and education, demonstrated that all subscales differentiated between healthy controls and psychotic patients (Wilks' Lambda = 0.87; F7, 226 = 4.70; p < .000; partial eta squared = 0.13). In addition, the DACOBS showed high correlations with PPLEs (controls) and moderate correlations with positive and general symptoms (patients), demonstrating its predictive validity. Concluding, the DACOBS proved to be a psychometrically suitable instrument for assessing cognitive biases in psychosis and adequately differentiated between patients and healthy individuals within the Spanish population. Norm scores are provided.

A Differential Profile of Biomarkers between Patients with Atrial Fibrillation and Healthy Controls.

Atrial fibrillation (AF) is explained by anatomical and electrophysiological changes in the atria determined by high pressure, dilatation, infiltration and inflammation in the myocardium. There are some biomarkers implicated in these processes, namely, NT-proBNP, high sensitivity troponin (Hs-Tn), urate, galectin-3, ST2, C reactive protein and fibrinogen. The aim of this study was to assess differences in these biomarkers between patients with AF and healthy controls. We designed a cross-sectional study consecutively including all patients undergoing electrical cardioversion in our hospital for persistent AF and matched healthy controls. We included 115 patients with persistent non-valvular AF and 33 healthy subjects. The biomarkers NT-proBNP, ST2 and Hs-Tn T were significantly related to the presence of AF (1054 ± 833.30 vs. 58.31 ± 59.40, p < 0.001; 35.43 ± 15.89 vs. 27.43 ± 10.95, p < 0.001 and 10.25 ± 6.11 vs. 8.42 ± 6.85, p < 0.001, respectively). NT-proBNP was the best biomarker differentiating AF patients (area under the curve 0.995). The best NT-proBNP cut-off point to differentiate AF was 102 pg/mL; for Hs-Tn T it was 11.5 ng/L and for ST2 it was 37.7 ng/mL. It is possible that these biomarkers intervene at the onset of AF and have no role in AF maintenance.

The Role of Depressive Disorders in Autonomic Cardiovascular Dysregulation in Fibromyalgia.

OBJECTIVE: Previous research revealed aberrances in autonomic cardiovascular regulation in fibromyalgia, which may be relevant to symptoms genesis and the increased risk of cardiovascular disorders in individuals with fibromyalgia. This study investigated the role of comorbid depression in autonomic cardiovascular dysregulations in fibromyalgia. METHODS: Cardiovascular recordings were obtained in 53 participants with fibromyalgia who also had depression ( n = 27), in participants with fibromyalgia without depression ( n = 26), and in 29 healthy controls, at rest and during a cold pressor test and an arithmetic task. Assessed parameters included interbeat interval, blood pressure, heart rate variability, baroreflex sensitivity, stroke volume, preejection period, left ventricular ejection time, Heather index, and total peripheral resistance. RESULTS: Participants with both fibromyalgia and depression displayed lower tonic interbeat interval, baroreflex sensitivity, and heart rate variability compared with participants with fibromyalgia without depression and controls ( p values < .012, d values = 0.71-1.06). Participants with fibromyalgia but without depression did not differ from controls in these variables. Moreover, participants with fibromyalgia who also had depression, but not those without depression, exhibited lower Heather index, stroke volume, and left ventricular ejection time compared with controls ( p values < .013, d values = 0.62-0.78). No group differences arose for preejection period or total peripheral resistance. Stress reactivity was reduced in participants with fibromyalgia, independently of depression, for diastolic blood pressure, interbeat interval, left ventricular ejection time, and heart rate variability, than in controls. CONCLUSIONS: The role of depression in the autonomic dysregulation in fibromyalgia involves chronotropic cardiac control rather than adrenergic influences on contractility and vascular tone. Blunted cardiovascular reactivity may be ascribable to pathological factors inherent to fibromyalgia. These results underline the importance of diagnostics and treatment of comorbid depressive disorders in the management of fibromyalgia.

An imaging flow cytometry-based methodology for the analysis of single extracellular vesicles in unprocessed human plasma.

Extracellular vesicles (EVs) are tissue-specific particles released by cells containing valuable diagnostic information in the form of various biomolecules. To rule out selection bias or introduction of artefacts caused by EV isolation techniques, we present a clinically feasible, imaging flow cytometry (IFCM)-based methodology to phenotype and determine the concentration of EVs with a diameter ≤400 nm in human platelet-poor plasma (PPP) without prior isolation of EVs. Instrument calibration (both size and fluorescence) were performed with commercial polystyrene beads. Detergent treatment of EVs was performed to discriminate true vesicular events from artefacts. Using a combination of markers (CFSE & Tetraspanins, or CD9 & CD31) we found that >90% of double-positive fluorescent events represented single EVs. Through this work, we provide a framework that will allow the application of IFCM for EV analysis in peripheral blood plasma in a plethora of experimental and potentially diagnostic settings. Additionally, this direct approach for EV analysis will enable researchers to explore corners of EVs as cellular messengers in healthy and pathological conditions.

Kidney Biopsy in Patients with Cancer along the Last Decade: A Multicenter Study.

BACKGROUND: Currently, following the new advances in cancer treatments and the increasing prevalence of kidney disease in the population, more kidney biopsies are being performed. The aim of our study is to analyze clinical and histological characteristics of patients with active solid organ malignancy who underwent kidney biopsy. This is a multi-center collaborative retrospective study supported by groups GLOSEN/Onconephrology from the Spanish Society of Nephrology. Clinical, demographical and histological data were collected. RESULTS: A total of 148 patients with cancer who underwent a kidney biopsy from 12 hospitals were included. 64.3% men and mean age of 66.9 years old. The indications for biopsy were acute renal injury (67.1%), proteinuria (17.1%), exacerbated chronic kidney disease (8.2%), and chronic kidney disease (7.5%). Most frequent malignances were lung (29.1%) and abdominal (25%), with 49.7% metastatic cancer. As oncospecific treatment, 28% received chemotherapy, 29.3% immunotherapy, 19.3% specific therapies, and 2.1% conservative treatment. At the time of kidney biopsy, median creatinine was of 2.58 mg/dL [1.81-4.1 (IQ 25-75)], median urine protein-to-creatinine ratio of 700 mg/g [256-2463 (IQ 25-75)] and 53.1% presented hematuria. The most frequent renal biopsy diagnoses were: acute interstitial nephritis (39.9%), acute tubular necrosis (8.8%), IgA nephropathy (7.4%) and membranous nephropathy (6.1%). Median follow-up was 15.2 months [5.7-31.4 (IQ 25-75)]. CONCLUSIONS: There is a new trend in kidney disease and cancer patients in terms of diagnosis and treatment. Acute interstitial nephritis has established itself as the most common kidney injury in patients with cancer who underwent a kidney biopsy. Renal biopsy is a valuable tool for diagnosis, treatment, and prognosis of solid organ cancer patients with kidney damage.

Blunted short-term autonomic cardiovascular reactivity to orthostatic and clinostatic challenges in fibromyalgia as an indicator of the severity of chronic pain.

Fibromyalgia is a long-term pain disorder that has been related to autonomic dysfunctions and reduced cardiovascular reactivity. We aimed to assess the dynamic short-term cardiovascular responses to postural changes in fibromyalgia. Thirty-eight women with fibromyalgia and thirty-six healthy women underwent the "Chronic Pain Autonomic Stress Test". Electrocardiogram, blood pressure and impedance cardiography were continuously recorded during active standing and lying down. Second-by-second values were derived over the first 30 s of each posture. Lower reactivity during the beginning of each position was observed in fibromyalgia sufferers compared to healthy women, with smaller responses seen during stand up in heart rate, blood pressure, cardiac output, total peripheral resistance, and pre-ejection period, and smaller changes during lying down in heart rate, cardiac output and total peripheral resistance. The magnitude of the autonomic adjustments to postural changes was inversely associated with the severity of clinical pain. These findings indicate an early impaired autonomic cardiovascular response to orthostatic and clinostatic challenges in fibromyalgia, suggesting less autonomic flexibility and adaptability to situational demands and challenges. Short-term second-by-second cardiovascular measures may be useful in the clinical assessment of fibromyalgia.