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.

sST2 and Galectin-3 genotyping in patients with persistent atrial fibrillation.

Genotyping of ST2 and galectin-3 in atrial fibrillation (AF) is not well analyzed. The aim of our study was to analyze the possible relationship between levels of sST2 and galectin-3 and three polymorphisms in patients with AF. We included 125 patients with persistent AF undergoing electric cardioversion. We analyzed sST2 and galectin-3 levels and three polymorphisms in peripheral blood samples. Rs2274273 was significantly related with levels of galectin-3. Rs1558648 was associated with levels of sST2 but rs13019803 were not. None of the polymorphisms were connected to the variation of biomarkers levels during the follow up. We found a relationship between rs2274273 and galectin-3 levels and rs1558648 and sST2 levels in patients with AF.

Proteomic Analysis of Mesenchymal Stromal Cell-Derived Extracellular Vesicles and Reconstructed Membrane Particles.

Extracellular vesicles (EV) derived from mesenchymal stromal cells (MSC) are a potential therapy for immunological and degenerative diseases. However, large-scale production of EV free from contamination by soluble proteins is a major challenge. The generation of particles from isolated membranes of MSC, membrane particles (MP), may be an alternative to EV. In the present study we generated MP from the membranes of lysed MSC after removal of the nuclei. The yield of MP per MSC was 1 × 105 times higher than EV derived from the same number of MSC. To compare the proteome of MP and EV, proteomic analysis of MP and EV was performed. MP contained over 20 times more proteins than EV. The proteins present in MP evidenced a multi-organelle origin of MP. The projected function of the proteins in EV and MP was very different. Whilst proteins in EV mainly play a role in extracellular matrix organization, proteins in MP were interconnected in diverse molecular pathways, including protein synthesis and degradation pathways and demonstrated enzymatic activity. Treatment of MSC with IFNγ led to a profound effect on the protein make up of EV and MP, demonstrating the possibility to modify the phenotype of EV and MP through modification of parent MSC. These results demonstrate that MP are an attractive alternative to EV for the development of potential therapies. Functional studies will have to demonstrate therapeutic efficacy of MP in preclinical disease models.

Ambrisentan use in a HIV-1 infected patient with end-stage renal disease and pulmonary hypertension: minimal removal by hemodialysis - a case report.

BACKGROUND: Ambrisentan is a selective endothelin receptor antagonist used for the treatment of pulmonary arterial hypertension (PAH). Little is known about ambrisentan removal by hemodialysis in patients with end-stage renal disease (ESRD). CASE PRESENTATION: A 53-year-old woman with HIV/hepatitis C virus (HCV) co-infection, PAH and ESRD on regular hemodialyis was admitted in our hospital due to refractory heart failure while on treatment with bosentan (125 mg twice daily) and tadalafil (20 mg once daily) for PAH and antiretroviral treatment (cART) including darunavir/cobicistat (800/150 mg once daily). Excessive exposure to bosentan due to drug interactions between bosentan and darunavir/cobicistat was suspected. Bosentan was replaced by ambrisentan, with progressive improvement in her clinical condition. Pre- and postdialyzer cocentrations of ambrisentan in plasma were determined and hemodialysis extraction ratio for ambrisentan was 2%. CONCLUSIONS: Our results suggest that hemodialysis results in minimal ambrisentan removal, and therefore no specific ambrisentan dosage adjustment seems to be required in ESRD patients undergoing hemodialysis.

Administration of Human MSC-Derived Extracellular Vesicles for the Treatment of Primary Sclerosing Cholangitis: Preclinical Data in MDR2 Knockout Mice.

Primary Sclerosing Cholangitis (PSC) is a progressive liver disease for which there is no effective medical therapy. PSC belongs to the family of immune-mediated biliary disorders and it is characterized by persistent biliary inflammation and fibrosis. Here, we explored the possibility of using extracellular vesicles (EVs) derived from human, bone marrow mesenchymal stromal cells (MSCs) to target liver inflammation and reduce fibrosis in a mouse model of PSC. Five-week-old male FVB.129P2-Abcb4tm1Bor mice were intraperitoneally injected with either 100 µL of EVs (± 9.1 × 109 particles/mL) or PBS, once a week, for three consecutive weeks. One week after the last injection, mice were sacrificed and liver and blood collected for flow cytometry analysis and transaminase quantification. In FVB.129P2-Abcb4tm1Bor mice, EV administration resulted in reduced serum levels of alkaline phosphatase (ALP), bile acid (BA), and alanine aminotransferase (ALT), as well as in decreased liver fibrosis. Mechanistically, we observed that EVs reduce liver accumulation of both granulocytes and T cells and dampen VCAM-1 expression. Further analysis revealed that the therapeutic effect of EVs is accompanied by the inhibition of NFkB activation in proximity of the portal triad. Our pre-clinical experiments suggest that EVs isolated from MSCs may represent an effective therapeutic strategy to treat patients suffering from PSC.

Immunomodulation By Therapeutic Mesenchymal Stromal Cells (MSC) Is Triggered Through Phagocytosis of MSC By Monocytic Cells.

Mesenchymal stem or stromal cells (MSC) are under investigation as a potential immunotherapy. MSC are usually administered via intravenous infusion, after which they are trapped in the lungs and die and disappear within a day. The fate of MSC after their disappearance from the lungs is unknown and it is unclear how MSC realize their immunomodulatory effects in their short lifespan. We examined immunological mechanisms determining the fate of infused MSC and the immunomodulatory response associated with it. Tracking viable and dead human umbilical cord MSC (ucMSC) in mice using Qtracker beads (contained in viable cells) and Hoechst33342 (staining all cells) revealed that viable ucMSC were present in the lungs immediately after infusion. Twenty-four hours later, the majority of ucMSC were dead and found in the lungs and liver where they were contained in monocytic cells of predominantly non-classical Ly6Clow phenotype. Monocytes containing ucMSC were also detected systemically. In vitro experiments confirmed that human CD14++ /CD16- classical monocytes polarized toward a non-classical CD14++ CD16+ CD206+ phenotype after phagocytosis of ucMSC and expressed programmed death ligand-1 and IL-10, while TNF-α was reduced. ucMSC-primed monocytes induced Foxp3+ regulatory T cell formation in mixed lymphocyte reactions. These results demonstrate that infused MSC are rapidly phagocytosed by monocytes, which subsequently migrate from the lungs to other body sites. Phagocytosis of ucMSC induces phenotypical and functional changes in monocytes, which subsequently modulate cells of the adaptive immune system. It can be concluded that monocytes play a crucial role in mediating, distributing, and transferring the immunomodulatory effect of MSC. Stem Cells 2018;36:602-615.

Normative Pentacam anterior and posterior corneal elevation measurements: effects of age, sex, axial length and white-to-white.

PURPOSE: To provide normal corneal elevation data for a large Caucasian population and to determine the impacts on these data of age, sex, axial length (AXL) and horizontal white-to-white (WW). SETTING: Centro Internacional de Oftalmología Avanzada, Madrid, Spain. DESIGN: Retrospective, cross-sectional, observational. METHODS: In this retrospective, cross-sectional, observational study, anterior and posterior corneal elevations were measured in 789 right eyes of subjects with no ocular disease at the thinnest corneal location in relation to a fixed 8-mm best-fit sphere using the Pentacam, and AXL and WW were measured with the IOLMaster. A multiple linear regression model was used to assess the effects of age, sex, AXL and WW on the elevation data. RESULTS: Mean subject age was 50.5 ± 15 years (range 17-93 years); 64% were women. Mean anterior and posterior corneal elevations were 1.99 ± 1.75 µm (- 7 to 10 µm) and 7.70 ± 5.7 µm (- 6 to 28 µm). Anterior corneal elevations were higher by 0.165 µm and 0.033 µm for every mm reduction in AXL and every year reduction in age, respectively. Sex and WW were not significant predictors of anterior elevations (R2 = 7.7%). Posterior corneal elevation increased by 0.186 µm/year of age, 0.707 µm/mm reduction in WW and 0.819 µm/mm reduction in AXL. This variable was also 0.866 µm greater in men (R2 = 34.4%). CONCLUSION: Anterior corneal elevations decrease with age and are higher for shorter AXL but are not influenced by sex or WW. Posterior corneal elevations increase with age, decreasing AXL, decreasing WW and are higher in men.

Epigenetic changes in umbilical cord mesenchymal stromal cells upon stimulation and culture expansion.

BACKGROUND: Mesenchymal stromal cells (MSCs) are studied for their immunotherapeutic potential. Prior to therapeutic use, MSCs are culture expanded to obtain the required cell numbers and, to improve their efficacy, MSCs may be primed in vitro. Culture expansion and priming induce phenotypical and functional changes in MSCs and thus standardisation and quality control measurements come in need. We investigated the impact of priming and culturing on MSC DNA methylation and examined the use of epigenetic profiling as a quality control tool. METHODS: Human umbilical cord-derived MSCs (ucMSCs) were cultured for 3 days with interferon (IFN)γ, transforming growth factor (TGF)ß or a multi-factor combination (MC; IFNγ, TGFß and retinoic acid). In addition, ucMSCs were culture expanded for 14 days. Phenotypical changes and T-cell proliferation inhibition capacity were examined. Genome-wide DNA methylation was measured with Infinium MethylationEPIC Beadchip. RESULTS: Upon priming, ucMSCs exhibited a different immunophenotype and ucMSC(IFNγ) and ucMSC(MC) had an increased capacity to inhibit T-cell proliferation. DNA methylation patterns were minimally affected by priming, with only one significantly differentially methylated site (DMS) in IFNγ- and MC-primed ucMSCs associated with autophagy activity. In contrast, 14 days after culture expansion, ucMSCs displayed minor phenotypical and functional changes but showed >4000 significantly DMSs, mostly concerning genes involved in membrane composition, cell adhesion and transmembrane signalling. DISCUSSION: These data show that DNA methylation of MSCs is only marginally affected by priming, whereas culture expansion and subsequent increased cellular interactions have a large impact on methylation. On account of this study, we suggest that DNA methylation analysis is a useful quality control tool for culture expanded therapeutic MSCs.

Aging of bone marrow- and umbilical cord-derived mesenchymal stromal cells during expansion.

BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) are used as experimental immunotherapy. Extensive culture expansion is necessary to obtain clinically relevant cell numbers, although the impact on MSCs stability and function is unclear. This study investigated the effects of long-term in vitro expansion on the stability and function of MSCs. METHODS: Human bone marrow-derived (bmMSCs) and umbilical cord-derived (ucMSCs) MSCs were in vitro expanded. During expansion, their proliferative capacity was examined. At passages 4, 8 and 12, analyses were performed to investigate the ploidy, metabolic stability, telomere length and immunophenotype. In addition, their potential to suppress lymphocyte proliferation and susceptibility to natural killer cell lysis was examined. RESULTS: BmMSCs and ucMSCs showed decreasing proliferative capacity over time, while their telomere lengths and mitochondrial activity remained stable. Percentage of aneuploidy in cultures was unchanged after expansion. Furthermore, expression of MSC markers and markers associated with stress or aging remained unchanged. Reduced capacity to suppress CD4 and CD8 T-cell proliferation was observed for passage 8 and 12 bmMSCs and ucMSCs. Finally, susceptibility of bmMSCs and ucMSCs to NK-cell lysis remained stable. CONCLUSIONS: We showed that after long-term expansion, phenotype of bmMSCs and ucMSCs remains stable and cells exhibit similar immunogenic properties compared with lower passage cells. However, immunosuppressive properties of MSCs are reduced. These findings reveal the consequences of application of higher passage MSCs in the clinic, which will help increase the yield of therapeutic MSCs but may interfere with their efficacy.

Endothelial microparticles mediate inflammation-induced vascular calcification.

Stimulation of endothelial cells (ECs) with TNF-α causes an increase in the expression of bone morphogenetic protein-2 (BMP-2) and the production of endothelial microparticles (EMPs). BMP-2 is known to produce osteogenic differentiation of vascular smooth muscle cells (VSMCs). It was found that EMPs from TNF-α-stimulated endothelial cells (HUVECs) contained a significant amount of BMP-2 and were able to enhance VSMC osteogenesis and calcification. Calcium content was greater in VSMCs exposed to EMPs from TNF-α-treated HUVECs than EMPs from nontreated HUVECs (3.56 ± 0.57 vs. 1.48 ± 0.56 µg/mg protein; P < 0.05). The increase in calcification was accompanied by up-regulation of Cbfa1 (osteogenic transcription factor) and down-regulation of SM22α (VSMC lineage marker). Inhibition of BMP-2 by small interfering RNA reduced the VSMC calcification induced by EMPs from TNF-α-treated HUVECs. Similar osteogenic capability was observed in EMPs from both patients with chronic kidney disease and senescent cells, which also presented a high level of BMP-2 expression. Labeling of EMPs with CellTracker shows that EMPs are phagocytized by VSMCs under all conditions (with or without high phosphate, control, and EMPs from TNF-α-treated HUVECs). Our data suggest that EC damage results in the release of EMPs with a high content of calcium and BMP-2 that are able to induce calcification and osteogenic differentiation of VSMCs.

CD154-CD40 T-cell co-stimulation pathway is a key mechanism in kidney ischemia-reperfusion injury.

Ischemia-reperfusion occurs in a great many clinical settings and contributes to organ failure or dysfunction. CD154-CD40 signaling in leukocyte-endothelial cell interactions or T-cell activation facilitates tissue inflammation and injury. Here we tested a siRNA anti-CD40 in rodent warm and cold ischemia models to check the therapeutic efficacy and anti-inflammatory outcome of in vivo gene silencing. In the warm ischemia model different doses were used, resulting in clear renal function improvement and a structural renoprotective effect. Renal ischemia activated the CD40 gene and protein expression, which was inhibited by intravenous siRNA administration. CD40 gene silencing improved renal inflammatory status, as seen by the reduction of CD68 and CD3 T-cell infiltrates, attenuated pro-inflammatory, and enhanced anti-inflammatory mediators. Furthermore, siRNA administration decreased a spleen pro-inflammatory monocyte subset and reduced TNFα secretion by splenic T cells. In the cold ischemia model with syngeneic and allogeneic renal transplantation, the most effective dose induced similar functional and structural renoprotective effects. Our data show the efficacy of our siRNA in modulating both the local and the systemic inflammatory milieu after an ischemic insult. Thus, CD40 silencing could emerge as a novel therapeutic strategy in solid organ transplantation.

Patient Management and Psychopharmacological Treatment Associated to Smoking Ban in an Acute Psychiatric Unit.

This study investigates differences in terms of clinical and treatment management in psychiatric hospitalization associated to smoking ban. We collected data regarding medication, socio-demographic and admission characteristics from all patients admitted to an acute psychiatric hospital before and after a smoking ban was in force. We also assessed a limited sample of patients before and after the ban regarding nicotine dependence, motivation to quit smoking and attitudes towards the ban. More number of leaves of absence and movement restrictions during the ban period occurred in comparison to the pre-ban period. On the contrary a lack of significant differences in terms of hospital stay (duration, rate of voluntary admissions and voluntary discharges), use of sedatives and doses of antipsychotics was found. A period of adjustment regarding the deal with leave of access and facilitate nicotine replacement treatment may help future psychiatric facilities planning smoking free policies.

Clinical observation, pharmacotherapy and referral on discharge of patients with anxiety disorder in a psychiatric emergency service.

INTRODUCTION: To analyze factors associated with clinical observation, pharmacotherapy and referral on discharge of patients with anxiety disorder (AD) seeking care at a psychiatric emergency unit. METHOD: A total of 5003 consecutive visits were reviewed over a three-year period at a psychiatric emergency service in a tertiary university hospital. Data collected included sociodemographic and clinical information as well as the Global Assessment of Functioning (GAF) and the Severity Psychiatric Illness (SPI) scale scores. RESULTS: Of all the visits, 992 (19.8%) were diagnosed of AD. Of these, 19.6% required clinical observation and 72.2% were referred to a psychiatrist at discharge. Regression analysis showed that referral to psychiatry was associated with being male, native, psychiatric background, greater severity, lower global functioning, and behavioral disorders. Clinical observation (in a box) was associated with being female, greater severity, and psychotic or behavioral symptoms. Prescription of benzodiazepines was associated with anxiety, no history of addiction, and lower global functioning. Antidepressants were associated with being a native, anxiety with no history of addiction, and lower functioning. Antipsychotics were associated with being native, psychiatric background (not addiction), anxiety, and lower functioning. CONCLUSION: Behavior, psychiatric background and illness severity were determinants of referral to a specialist. Besides these, psychotic symptoms and non-specific clinical symptoms were determinants of observation. Drug prescription in AD is less frequent if the main complaint is not anxiety and depends more on the level of functioning than on that of severity.

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.

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 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.

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.

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.

Senescent CD14+CD16+ monocytes exhibit proinflammatory and proatherosclerotic activity.

In elderly subjects and in patients with chronic inflammatory diseases, there is an increased subset of monocytes with a CD14(+)CD16(+) phenotype, whose origin and functional relevance has not been well characterized. In this study, we determined whether prolonged survival of human CD14(++)CD16(-) monocytes promotes the emergence of senescent cells, and we analyzed their molecular phenotypic and functional characteristics. We used an in vitro model to prolong the life span of healthy monocytes. We determined cell senescence, intracellular cytokine expression, ability to interact with endothelial cells, and APC activity. CD14(+)CD16(+) monocytes were senescent cells with shortened telomeres (215 ± 37 relative telomere length) versus CD14(++)CD16(-) cells (339 ± 44 relative telomere length; p < 0.05) and increased expression of ß-galactosidase (86.4 ± 16.4% versus 10.3 ± 7.5%, respectively; p = 0.002). CD14(+)CD16(+) monocytes exhibited features of activated cells that included expression of CD209, release of cytokines in response to low-intensity stimulus, and increased capacity to sustain lymphocyte proliferation. Finally, compared with CD14(++)CD16(-) cells, CD14(+)CD16(+) monocytes showed elevated expression of chemokine receptors and increased adhesion to endothelial cells (19.6 ± 8.1% versus 5.3 ± 4.1%; p = 0.033). In summary, our data indicated that the senescent CD14(+)CD16(+) monocytes are activated cells, with increased inflammatory activity and ability to interact with endothelial cells. Therefore, accumulation of senescent monocytes may explain, in part, the development of chronic inflammation and atherosclerosis in elderly subjects and in patients with chronic inflammatory diseases.