Pituitary-Adrenal Axis and Peripheral Immune Cell Profile in Long COVID.

In Long COVID, dysfunction in the pituitary-adrenal axis and alterations in immune cells and inflammatory status are warned against. We performed a prospective study in a cohort of 42 patients who suffered COVID-19 at least 6 months before attending the Long COVID unit at Althaia Hospital. Based on Post-COVID Functional Status, 29 patients were diagnosed with Long COVID, while 13 were deemed as recovered. The hormones of the pituitary-adrenal axis, adrenocorticotropin stimulation test, and immune cell profiles and inflammatory markers were examined. Patients with Long COVID had significantly lower EuroQol and higher mMRC scores compared to the recovered individuals. Their symptoms included fatigue, myalgia, arthralgia, persistent coughing, a persistent sore throat, dyspnoea, a lack of concentration, and anxiety. We observed the physiological levels of cortisol and adrenocorticotropin in individuals with or without Long COVID. The results of the adrenocorticotropin stimulation test were similar between both groups. The absolute number of neutrophils was lower in the Long COVID patients compared to recovered individuals (p < 0.05). The total count of B lymphocytes remained consistent, but Long COVID patients had a higher percentage of mature B cells compared to recovered participants (p < 0.05) and exhibited a higher percentage of circulating resident memory CD8+ T cells (p < 0.05) and Treg-expressing exonucleases (p < 0.05). Our findings did not identify adrenal dysfunction related to Long COVID, nor an association between adrenal function and clinical symptoms. The data indicated a dysregulation in certain immune cells, pointing to immune activation. No overt hyperinflammation was observed in the Long COVID group.

Effectiveness and Safety of Teriflunomide in Relapsing-Remitting Multiple Sclerosis and Improvements in Quality of Life: Results from the Real-World TERICARE Study.

INTRODUCTION: Teriflunomide is a once-daily oral immunomodulator approved for relapsing forms of multiple sclerosis (MS) or relapsing-remitting multiple sclerosis (RRMS; depending on the local label), based on extensive evidence from clinical trials and a real-world setting on efficacy, tolerability and patient-reported benefits. The TERICARE study assessed the impact of teriflunomide treatment over 2 years on health-related quality of life (HRQoL) and some of the most common and disabling symptoms of MS, such as fatigue and depression. METHODS: This prospective observational study in Spain included RRMS patients treated with teriflunomide for ≤ 4 weeks. The following patient-reported outcomes (PROs) were collected at baseline and every 6 months for 2 years: the 29-item Multiple Sclerosis Impact Scale version 2 (MSIS-29), the 21-item Modified Fatigue Impact Scale (MFIS-21), the Beck Depression Inventory (BDI-II), the Short Form (SF)-Qualiveen and the Treatment Satisfaction Questionnaire for Medication v1.4 (TSQM). Annualised relapse rate (ARR), disability progression according to the Expanded Disability Status Scale (EDSS), and no evidence of disease activity (NEDA-3) were also assessed. RESULTS: A total of 325 patients were analysed. Patients had a mean (SD) age of 43.2 years (10.4), a mean baseline EDSS score of 1.75 (1.5), a mean number of relapses in the past 2 years of 1.5 (0.7), and 64% had received prior disease-modifying therapy (DMT). Patients showed significant improvements in the psychological domain of MSIS-29 from 35.9 (26.6) at baseline to 29.4 (25.5) at 18 months (p = 0.004) and 29.0 (24.6) at 24 months (p = 0.002). Levels of fatigue and depression were also reduced. After 2 years of treatment with teriflunomide, ARR was reduced to 0.17 (95% CI 0.14-0.21) from the baseline of 0.42 (95% CI 0.38-0.48), representing a 60.1% reduction. Mean EDSS scores remained stable during the study, and 79.9% of patients showed no disability progression. 54.7% of patients achieved NEDA-3 in the first 12 months, which increased to 61.4% during months 12-24. Patients reported increased satisfaction with treatment over the course of the study, regardless of whether they were DMT naive or not. CONCLUSION: Teriflunomide improves psychological aspects of HRQoL and maintains low levels of fatigue and depression. Treatment with teriflunomide over 2 years is effective in reducing ARR and disability progression.

A ternary eutectic solvent for cellulose nanocrystal production: exploring the recyclability and pre-pilot scale-up.

Deep eutectic solvents (DES) formed using choline chloride (ChCl), p-toluenesulfonic acid (pTSA) of stoichiometry ChCl: pTSA (1:1) and (1:2), and its ternary eutectic mixtures with phosphoric acid (PA) 85% as an additive (ChCl: pTSA: PA) were evaluated for cellulose nanocrystal (CNC) isolation. Initially, the hydrolytic efficiency to produce CNC of each DES was compared before and after adding phosphoric acid by Hammett acidity parameters and the Gutmann acceptor number. Moreover, different DES molar ratios and reaction time were studied at 80°C for CNC optimization. The nanomaterial characteristics were analyzed by field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). The ternary eutectic mixture ChCl: pTSA: PA molar ratio (1:1:1.35) was chosen as a suitable recyclable ternary system at the laboratory scale. A CNC yield of about 80% was obtained from the hydrolysis of commercial cellulose in five cycles of recovery, but it dropped to 35% in pre-pilot scaling. However, no variation in the average size of the resulting CNC was observed (132 ± 50 nm x 23 ± 4 nm), which presented high thermal stability (Tmax 362°C) and high crystallinity of about 80% after 3 h of reaction time.

Immunomodulation of Oxidative Stress during Organ Donation Process: Preliminary Results.

The objective was to quantify oxidative stress resulting from ischemia during the donation process, using malondialdehyde (MDA) measurement, and its modulation by the administration of melatonin. We designed a triple-blind clinical trial with donors randomized to melatonin or placebo. We collected donors by donation after brain death (DBD) and controlled donation after circulatory death (DCD), the latter maintained by normothermic regional perfusion (NRP). Melatonin or placebo was administered prior to donation or following limitation of therapeutic effort (LTE). Demographic variables and medical history were collected. We also collected serial measurements of MDA, at 60 and 90 min after melatonin or placebo administration. A total of 53 donors were included (32 from DBD and 21 from DCD). In the DBD group, 17 donors received melatonin, and 15 placebo. Eight DCD donors were randomized to melatonin and 13 to placebo. Medical history and cause for LTE were similar between groups. Although MDA values did not differ in the DBD group, statistical differences were observed in DCD donors during the 0-60 min interval: -4.296 (-6.752; -2.336) in the melatonin group and -1.612 (-2.886; -0.7445) in controls. Given the antioxidant effect of melatonin, its use could reduce the production of oxidative stress in controlled DCD.

Tumour Markers in the Differential Diagnosis of Patients With Isolated Involuntary Weight Loss.

BACKGROUND/AIM: Paraneoplastic syndrome symptoms include isolated involuntary weight loss (IIWL). The differential diagnosis of cancer from other diseases may require a significant number of tests. Tumour markers (TMs) can be used for the diagnosis and stratification of patients according to cancer risk. PATIENTS AND METHODS: This study included 606 patients (48% females) seen at the rapid diagnostic unit for IIWL. We determined the levels of TMs carcinoembryonic antigen, carbohydrate antigen 19-9, soluble fragments of cytokeratin 19, carbohydrate antigen 15-3, carbohydrate antigen 125, neuron specific enolase, alpha-fetoprotein, prostatic specific antigen using the multiparametric analyser COBAS 601. Two cut-off points were established, the upper reference limit described by the manufacturer and a high cut-off point suggested by Molina et al., to stratify patients according to cancer risk. RESULTS: Patients were classified according to TM levels as follows: I) all TMs below the upper reference limit; II) highest number of TMs between the two cut-offs; III) at least one TM above the higher cut-off. The odds ratio for malignancy was 4.3 for group II and 248 for group III. These results indicate that when at least one TM is above the higher cut-off, neoplasia is highly probable. CONCLUSION: TM determination allowed to establish cancer risk in patients with IIWL.

Etiologies and 12-month mortality in patients with isolated involuntary weight loss at a rapid diagnostic unit.

BACKGROUND: Numerous studies on involuntary weight loss (IWL) have been published since the 1980s, although most of them have included small samples of patients with specific symptoms. The aim of the present study was to determine the causes, demographic and clinical characteristics and mortality at 12 months in patients attended at a rapid diagnostic unit (RDU) for isolated IWL. METHODS: A single-center retrospective observational study including all patients presenting to the RDU for isolated IWL between 2005 and 2013. The following data were recorded: demographic and clinical variables, results of complementary tests (blood tests, x-rays, computed tomography scan and digestive endoscopy), main diagnosis and vital status at 12 months. RESULTS: Seven hundred and ninety-one patients met the criteria for IWL. Mean age was 67.9 years (SD 4.7), 50.4% were male and mean weight loss was 8.3 kg (SD 4.7). The cause for IWL was malignant disease in 23.6% of patients, non-malignant organic disease in 44.5%, psychiatric disorder in 29.0% and unknown in 3.2%. Overall mortality at 12 months was 18.6% (95%CI: 16.1-21.6). The mortality rate was highest in the group with malignancy (61.1%; 95%CI: 54.2-68.2). CONCLUSIONS: Almost a quarter of all patients attended at the RDU for IWL were diagnosed with cancer. Mortality at 12 months was higher in this group than in the other three. Malignancy should therefore be ruled out during the first visit for patients attended for IWL.

Visual and Hearing Impairment Are Associated With Delirium in Hospitalized Patients: Results of a Multisite Prevalence Study.

OBJECTIVE: Sensory deficits are important risk factors for delirium but have been investigated in single-center studies and single clinical settings. This multicenter study aims to evaluate the association between hearing and visual impairment or bi-sensory impairment (visual and hearing impairment) and delirium. DESIGN: Cross-sectional study nested in the 2017 "Delirium Day" project. SETTING AND PARTICIPANTS: Patients 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes, and hospices in Italy. METHODS: Delirium was assessed with the 4AT (a short tool for delirium assessment) and sensory deficits with a clinical evaluation. We assessed the association between delirium, hearing and visual impairment in multivariable logistic regression models, adjusting for: Model 1, we included predisposing factors for delirium (ie, dementia, weight loss and autonomy in the activities of daily living); Model 2, we added to Model 1 variables, which could be considered precipitating factors for delirium (ie, psychoactive drugs and urinary catheters). RESULTS: A total of 3038 patients were included; delirium prevalence was 25%. Patients with delirium had a higher prevalence of hearing impairment (30.5% vs 18%; P < .001), visual impairment (24.2% vs 15.7%; P < .01) and bi-sensory impairment (16.2% vs 7.5%) compared with those without delirium. In the multivariable logistic regression analysis, the presence of bi-sensory impairment was associated with delirium in Model 1 [odds ratio (OR) 1.5, confidence interval (CI) 1.2-2.1; P = .00] and in Model 2 (OR 1.4; CI 1.1-1.9; P = .02), whereas the presence of visual and hearing impairment alone was not associated with delirium either in Model 1 (OR 0.8; CI 0.6-1.2, P = .36; OR 1.1; CI 0.8-1.4; P = .42) or in Model 2 (OR 0.8, CI 0.6-1.2, P = .27; OR 1.1, CI 0.8-1.4, P = .63). CONCLUSIONS AND IMPLICATIONS: Our findings support the importance of routine screening and specific interventions by a multidisciplinary team to implement optimal management of sensory impairments and hence prevention and the management of the patients with delirium.

Comparative Assessment of Two Strategies for Interpreting Tumor Markers in Ascitic Effusions.

BACKGROUND/AIM: There are two strategies for the interpretation of tumor markers (TM) in fluid effusions: i) high cut-off and ii) fluid/serum ratio (F/S) and low cut-off. The objective of this study is to compare these two strategies and to determine whether diagnostic accuracy improves by the identification of possible false positives using Adenosine deaminase (ADA), C reactive protein (CRP) and % of polymorphonuclear cells (%PN). PATIENTS AND METHODS: We studied 157 ascitic fluids, 74 of which were malignant. ADA, CRP and %PN were determined in ascitic fluid, and Carcinoembryonic antigen (CEA), Cancer antigen 72-4 (CA72-4), Cancer antigen CA19-9 and Cancer antigen 15-3 (CA15-3) in both fluid and serum. RESULTS: The strategy of high cut-off showed 59.5% sensitivity at 100% specificity. The F/S strategy showed 75.7% sensitivity at 95.2% specificity. Subclassifying cases with ADA, CRP and %PN negative showed 67.5% sensitivity at 100% specificity for high cut-off and for the F/S strategy was 81.7% sensitivity at 98.7% specificity. CONCLUSION: The strategy of F/S with negative ADA, CRP and %PN allow the best interpretation for TM in the ascitic fluid.

Medicina intensiva: la columna vertebral del proceso de donación en España / Intensive Care Medicine: The cornerstone of the donation process in Spain

No disponible

Systemic lupus erythematosus and hydroxychloroquine-related acute intermittent porphyria.

Porphyrias, particularly acute intermittent porphyria (AIP), are rare disorders which could be associated with systemic lupus erythematosus (SLE). Although the association with AIP has been known since 1952, only 11 cases have been published to date. It is widely known that precipitating causes such as infections, hormonal changes, sunlight exposure, stress and drugs could provoke an AIP crisis. Hydroxychloroquine (HCQ) is usually used in lupus patients, but rarely appears to trigger AIP crises even in SLE patients. The case of a 51-year-old man in whom AIP onset was probably due to hydroxychloroquine use during SLE management is presented. SLE onset was accompanied by fever, pleural, lung and joint involvement with a characteristic SLE autoantibody panel. Although prednisone was given, the joint symptoms did not subside. HCQ was then started; however, some days later the patient suffered anxiety, vomiting and severe abdominal pain refractory to pain-relief drugs and liver function had worsened. No cutaneous lesions were observed. The patient suffered similar episodes accompanied by paralytic ileus and dark-coloured urine, the sediment of which showed no abnormalities. In addition, no myoglobinuria was found. This finding raised the suspicion of AIP and urine tests revealed elevated values of delta-aminolevulinic acid and porphobilinogen. Hydroxychloroquine was preventively suspended and the patient improved notably within a few days. In the following months, the patient suffered no relapse and the prednisone dose could be lowered. Finally, a review of the literature on this topic highlighted the exceptional nature of an API/ SLE association particularly in men. Interestingly, porphyria may present first followed by SLE, or vice versa. The latency period between drug administration and disease onset varies from days to 2 years. Both chloroquine and HCQ may induce PAI in SLE patients. Clinicians should be alerted to a possible association with AIP when a patient with SLE recently put on HCQ presents acute onset of abdominal and/or neurological symptoms and dark urine. Appropriate tests and prompt HCQ cessation are mandatory.

Diagnostic Accuracy of CYFRA21-1 in the Differential Diagnosis of Pleural Effusions.

BACKGROUND/AIM: Approximately 20% of pleural effusions are associated with cancer; about 50% require invasive procedures to perform diagnosis. Determination of the concentration of soluble cytokeratin 19-fragments (CYFRA21-1) may help identify patients with malignant effusions. However, pathologies other than cancer can increase its concentration. The identification of these possible false positives with routine tests CRP, ADA, % polymorphonuclear cells (PN) may improve diagnostic accuracy. This study aimed to determine the diagnostic accuracy of CYFRA21-1 in the detection of malignant pleural effusions and the possible false positives. MATERIALS AND METHODS: Analysis of CYFRA21-1, adenosine deaminase (ADA), C-reactive protein (CRP), and the percentage of polymorphonuclear leukocytes (PN%) in the fluid from 643 consecutive undiagnosed pleural effusions was performed. RESULTS: CYFRA21-1 showed 38.7% sensitivity and 97.3% specificity at 175 ng/ml cut-off. Effusions not suspicious of a false-positive showed 39.0% sensitivity and 98.2% specificity, while effusions suspicious of false positive showed lower sensitivity (36.4%) and specificity (95.0%). CONCLUSION: The diagnostic accuracy of CYFRA21-1 in pleural effusions can be improved by classification according to the possibility of false positives.

Long-term Impact of Hip Fracture on the Use of Healthcare Resources: a Population-Based Study.

OBJECTIVES: To assess the impact of hip fracture (HF) on health care expenditures and resource use. DESIGN: Observational, retrospective study. An administrative registry was used to obtain sociodemographic, clinical, and expenditure data of patients treated in centers all over Catalonia (North-East Spain). SETTING AND PARTICIPANTS: Male and female patients aged 65 years or older admitted to a Catalonian hospital due to hip fracture (HF) between January 1 2012, and December 31, 2016. MEASURES: The study data set included the expenditure and frequency of using nonemergency transport, rehabilitation, skilled nursing facility, specialist visits, admissions to the emergency department, hospitalization, pharmacy, and primary care. The patient status at each time point included living at home, staying in hospital, staying in a skilled nursing facility, institutionalized in a nursing home, and death. RESULTS: The record included 38,628 patients (74.4% female) with a mean [standard deviation (SD)] age of 84.9 (7.07) years. The average expenditure per patient during the first year after hospital admission was €11,721.06, the index hospitalization being the leading expenditure (€4740.29). Expenditures related to hospitalization and skilled nursing facility remained higher than preinjury throughout the 3 years following HF. Three years after the index admission, 44.9% of patients had died, 39.7% were living in their homes, 14.2% were in a nursing home, 0.9% were in a skilled nursing facility, and 0.3% were in hospital. The expenditure of hospitalizations, primary care, and visits to the emergency department increased few months before the HF. CONCLUSIONS: In patients hospitalized for HF, the expenditure per patient decreases after hospital discharge but the use of healthcare resources is not restored to preinjury values. The increase of expenditures associated with primary care services, hospitalization, and emergency department services during the few months preceding hospital admission suggests a decline of health status in these patients.

Hip fractures in the oldest old. Comparative study of centenarians and nonagenarians and mortality risk factors.

INTRODUCTION: Centenarians and nonagenarians constitute a rapidly growing age group in Western countries and they are expected to be admitted to hospital with hip fractures. The aim of this study was to compare outcomes of centenarian and nonagenarian patients following a hip fracture and to identify risk factors related to in-hospital and post-discharge mortality in both groups. PATIENTS AND METHODS: A prospective evaluation of centenarian patients and nonagenarian controls admitted to a tertiary university hospital in Barcelona with hip fractures over a period of 5 years and 9 months. Baseline characteristics and outcomes in both patient groups were compared. Variables associated with in-hospital, 30-day, 3-month and 1-year mortality were also analyzed. RESULTS: Thirty-three centenarians and 82 nonagenarians were included. The most relevant statistically significant differences found were: Barthel index at admission (61.90 vs. 75.22), number of drugs before admission (4.21vs 5.55), in-hospital complication rates (97 vs. 78%), readmissions at 3 months and 1 year (0 vs 11.7% and 3.4 vs. 19.5% respectively) and mortality at 3 months and 1 year (41.4 vs. 20.8% and 62.1 vs. 29.9%, respectively). Mean number of complications, rapid atrial fibrillation, mean age, and urinary tract infection were risk factors associated with mortality. CONCLUSIONS: Centenarian patients had similar in-hospital outcomes to nonagenarians, but experienced more complications and twice the 3-month and 1-year mortality rate. The mean number of complications was the risk factor most consistently related to in-hospital and post-discharge mortality. These findings emphasize the need to improve care in very old patients to prevent complications.

Influence of demographic and clinical characteristics of elderly patients with a hip fracture on mortality: A retrospective, total cohort study in North-East Spain.

IMPORTANCE: The increased mortality after hip fracture (HF) is caused by multiple factors, and large samples are needed to assess the weight of each factor. To date, few studies have investigated these factors through a total cohort approach, and the complexity of underlying medical conditions has not been considered. OBJECTIVE: To investigate the influence of demographic and clinical characteristics on increased mortality risk in elderly patients with hip fracture (HF). DESIGN: Retrospective, total cohort study collecting 4-year data. SETTING: All hospitals and primary care units owned by, or associated with, Catalonia's local health department (CatSalut) (north-east Spain). PARTICIPANTS: All patients aged ≥65 years, admitted to Catalan hospitals from CatSalut because of a HF between 1st January 2012 and 31st December 2015. EXPOSURE: Hip fracture. MAIN OUTCOME MEASURES: The main outcome was survival. Measures regarding demographic and clinical characteristics at the moment of hospital admission included age, sex, osteoporosis treatment, previous fractures, type of intervention, nutritional status, and comorbidities. Patients were stratified using the Adjusted Morbidity Groups (GMA) risk assessment tool. RESULTS: Of the 30,552 patients included in the study sample, 10,439 (34%) died during follow-up, 6821 (22%) within the first year after hospital admission. Mean (SD) age was 84 (7) years; 75% were female. Baseline factors with greater influence on survival were age (HRs 1.44 [95% CI 1.22-1.70], 2.38 [2.03-2.79], and 4.38 [3.73-5.15] for age groups 70-79, 80-89, and >89, respectively), underweight (HR 1.65 [1.36-2.01]), lack of surgical intervention (HR 2.64 [2.47-2.83]), and very high risk stratum of GMA risk (HR 1.58 [1.45-1.73]). Vitamin D/calcium supplementation and osteoporosis treatment showed a significant but moderate influence on mortality (HRs 0.84 (0.79-0.88) and 0.92 [0.85-0.99], respectively). CONCLUSIONS AND RELEVANCE: In elderly patients with HF, age and health status factors at hospital admission have the greatest impact on mortality risk after hospital admission. Our findings encourage a comprehensive intervention aimed at improving underlying medical conditions of HF patients.

Clinical study of hyaluronic acid gel in dyspareunia caused by vaginal dryness / Estudio clínico con un gel de ácido hialurónico en la dispareunia por sequedad vaginal

Objective: Hyaluronic acid plays a key role in the hydration, elasticity, and lubrication of the vagina. We evaluated the efficacy of a hyaluronic acid gel (Hyaluron mucus(R)) in the treatment of dyspareunia due to vaginal dryness. Material and methods: A total of 150 women applied the gel using their fingers before intercourse. The gel could also be applied simultaneously by the partner. We assessed the intensity of pain, discomfort during intercourse, and degree of vaginal dryness; we also recorded overall opinion (physician and/or patient) on the efficacy and tolerability of the gel and on its cosmetic and medical properties. Adverse effects and their causality were also recorded. Results: An improvement in pain, discomfort during intercourse, and vaginal dryness was reported by 91%, 84%, and 92% of patients, respectively. Medical opinion was favorable in 81% of cases and moderate in the remaining 19%. Patient opinion was favorable in 82%, moderate in 15%, and poor in 3%. Tolerability was good (2 cases of pruritus, 3 of stinging, and 1 of burning sensation). Compared with the previous treatment, the new gel was considered better by 64% of the women, equal or similar by 33%, and worse by 4%. Conclusions: The hyaluronic acid gel studied (Hyaluron mucus(R)) significantly improved vaginal dryness and dyspareunia with good tolerability and favorable cosmetic-medical properties in around 90% of cases

Objetivo: el ácido hialurónico es clave en la hidratación, elasticidad y lubricación vaginal. Hemos valorado la eficacia de un gel de ácido hialurónico (Hyaluron mucus(R)) en el tratamiento de la dispareunia asociada a sequedad vaginal. Material y métodos: 150 mujeres se aplicaron el gel en la vagina digitalmente antes de cada relación sexual, y se dejó abierta la posibilidad de que se aplicara simultáneamente por la pareja. Se valoraron la intensidad del dolor, la dificultad en la relación y el grado de sequedad vaginal; se registró la opinión global (del médico y/o del paciente) sobre la eficacia, la tolerabilidad y las características cosmético-galénicas del gel. También se recogieron los efectos adversos y su imputabilidad. Resultados: el dolor, la dificultad en la relación y la sequedad vaginal mejoraron en el 91%, el 84% y el 92%, respectivamente. El juicio médico global fue bueno para el 81% de los casos y moderado en el 19% restante, para las pacientes fue bueno en el 82%, moderado en el 15% y malo en un 3%. La tolerabilidad ha sido buena (2 casos de prurito, 3 de escozor y 1 de quemazón). El gel en estudio fue considerado mejor por el 64% de las mujeres, igual o semejante por el 33% y peor por el 4%, respecto al tratamiento previo. Conclusiones: el gel de ácido hialurónico estudiado mejora de forma relevante en torno al 90% de los casos la sequedad vaginal y la dispareunia con una buena tolerabilidad y aceptabilidad cosmeto-galénica

AMPA Receptor Antagonist CFM-2 Decreases Survivin Expression in Cancer Cells.

BACKGROUND: Glutamate receptors are widely expressed in different types of cancer cells. α-Amino-3- hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors are ionotropic glutamate receptors which are coupled to intracellular signaling pathways that influence cancer cell survival, proliferation, and migration. Blockade of AMPA receptors by pharmacologic compounds may potentially constitute an effective tool in anticancer treatment strategies. METHOD: Here we investigated the impact of the AMPA receptor antagonist CFM-2 on the expression of the protein survivin, which is known to promote cancer cell survival and proliferation. We show that CFM-2 inhibits survivin expression at mRNA and protein levels and decreases the viability of cancer cells. Using a stably transfected cell line which overexpresses survivin, we demonstrate that over-expression of survivin enhances cancer cell viability and attenuates CFM-2-mediated inhibition of cancer cell growth. RESULT: These findings point towards suppression of survivin expression as a new mechanism contributing to anticancer effects of AMPA antagonists.

Hip Fractures in People Older Than 95 Years: Are Patients Without Age-Associated Illnesses Different?

Background: Patients older than 95 years of age can be categorized according to three morbidity profiles: escapers, delayers, and survivors. The aim of this study was to describe the baseline characteristics, in-hospital outcomes, and cumulative mortality of extremely elderly patients admitted with hip fractures and to examine whether there were differences between patients without age-related illnesses (escapers) and others in the same age group (survivors when age-associated illnesses were diagnosed before the age of 80, delayers when these illnesses appeared after the age of 80). Methods: A retrospective review of clinical and outcome data of all patients older than 95 years of age admitted with hip fractures. Results: Two hundred patients older than 95 years were admitted with hip fractures between December 2009 and September 2015. Eighty-six per cent of patients had at least one in-hospital complication. In-hospital mortality was 12.5 per cent; cumulative mortality rates at 30 days, 3 months, and 1 year were 20.3, 30.8, and 50.5 per cent, respectively. There were 15 (7.5%) escaper patients. Compared with other patients with age-related illnesses, they took fewer drugs, had lower Charlson scores, a higher Barthel index score, shorter length of hospital stay, less delay in surgery, and more often required discharge to an in-patient rehabilitation facility. No differences in cumulative mortality were noted. Conclusions: Escaper patients had better baseline characteristics, shorter length of hospital stay, and delay in surgery. Nevertheless, their in-hospital and cumulative mortality rates were similar to those of other patients older than 95 years.

Exploring APOE genotype effects on Alzheimer's disease risk and amyloid ß burden in individuals with subjective cognitive decline: The FundacioACE Healthy Brain Initiative (FACEHBI) study baseline results.

INTRODUCTION: Subjective cognitive decline (SCD) has been proposed as a potential preclinical stage of Alzheimer's disease (AD). Nevertheless, the genetic and biomarker profiles of SCD individuals remain mostly unexplored. METHODS: We evaluated apolipoprotein E (APOE) ε4's effect in the risk of presenting SCD, using the Fundacio ACE Healthy Brain Initiative (FACEHBI) SCD cohort and Spanish controls, and performed a meta-analysis addressing the same question. We assessed the relationship between APOE dosage and brain amyloid burden in the FACEHBI SCD and Alzheimer's Disease Neuroimaging Initiative cohorts. RESULTS: Analysis of the FACEHBI cohort and the meta-analysis demonstrated SCD individuals presented higher allelic frequencies of APOE ε4 with respect to controls. APOE dosage explained 9% (FACEHBI cohort) and 11% (FACEHBI and Alzheimer's Disease Neuroimaging Initiative cohorts) of the variance of cerebral amyloid levels. DISCUSSION: The FACEHBI sample presents APOE ε4 enrichment, suggesting that a pool of AD patients is nested in our sample. Cerebral amyloid levels are partially explained by the APOE allele dosage, suggesting that other genetic or epigenetic factors are involved in this AD endophenotype.

Potentially Inappropriate Antihypertensive Prescriptions to Elderly Patients: Results of a Prospective, Observational Study.

INTRODUCTION: Previous studies of antihypertensive treatment of older patients have focused on blood pressure control, cardiovascular risk or adherence, whereas data on inappropriate antihypertensive prescriptions to older patients are scarce. OBJECTIVES: The aim of the study was to assess inappropriate antihypertensive prescriptions to older patients. METHODS: An observational, prospective multicentric study was conducted to assess potentially inappropriate prescription of antihypertensive drugs, in patients aged 75 years and older with arterial hypertension (HTN), in the month prior to hospital admission, using four instruments: Beers, Screening Tool of Older Person's Prescriptions (STOPP), Screening Tool to Alert Doctors to the Right Treatment (START) and Assessing Care of Vulnerable Elders 3 (ACOVE-3). Primary care and hospital electronic records were reviewed for HTN diagnoses, antihypertensive treatment and blood pressure readings. RESULTS: Of 672 patients, 532 (median age 85 years, 56% female) had HTN. 21.6% received antihypertensive monotherapy, 4.7% received no hypertensive treatment, and the remainder received a combination of antihypertensive therapies. The most frequently prescribed antihypertensive drugs were diuretics (53.5%), angiotensin-converting enzyme inhibitors (ACEIs) (41%), calcium antagonists (32.2%), angiotensin receptor blockers (29.7%) and beta-blockers (29.7%). Potentially inappropriate prescription was observed in 51.3% of patients (27.8% overprescription and 35% underprescription). The most frequent inappropriately prescribed drugs were calcium antagonists (overprescribed), ACEIs and beta-blockers (underprescribed). ACEI and beta-blocker underprescriptions were independently associated with heart failure admissions [beta-blockers odds ratio (OR) 0.53, 95% confidence interval (CI) 0.39-0.71, p < 0.001; ACEIs OR 0.50, 95% CI 0.36-0.70, p < 0.001]. CONCLUSION: Potentially inappropriate prescription was detected in more than half of patients receiving antihypertensive treatment. Underprescription was more frequent than overprescription. ACEIs and beta-blockers were frequently underprescribed and were associated with heart failure admissions.