Approach to the elderly patient with vertebral fracture due to bone fragility. / Abordaje del adulto mayor con fractura vertebral por fragilidad osea.

Osteoporosis is a metabolic and systemic disease characterized by alterations at the level of bone tissue with loss of bone mineral density, changes in microarchitecture, mineralization and remodeling that determine greater bone fragility and risk of fracture. Falls in the elderly are a risk factor closely related to fragility fractures and numerous studies demonstrate this relationship. Vertebral fractures are a major cause of morbidity and mortality. The epidemiology differs from osteoporotic fractures at other skeletal sites, as only one-third are clinically recognized. In the elderly, the approach to osteoporotic vertebral fracture involves comprehensive evaluation of the patient, since it is both a cause and a consequence of multiple geriatric syndromes. This fracture, in its acute phase and subsequently, can lead to destabilization of other organs and systems of the elderly, medical complications at different levels, functional deterioration, dependence, and even the need for institutionalization. Therefore, it is important to carry out a multiple assessment of patients with vertebral fractures, addressing not only the history and risk factors of osteoporosis, but also those factors that lead to falls, as well as a comprehensive geriatric assessment and the complications closely associated with it. In this chapter we address each of these aspects that are necessary in the individual and multidimensional approach to the elderly patient with vertebral fracture due to bone fragility.

In Vivo Predictive Dissolution and Biopharmaceutic-Based In Silico Model to Explain Bioequivalence Results of Valsartan, a Biopharmaceutics Classification System Class IV Drug.

The purpose of this study was to predict the in vivo bioequivalence (BE) outcome of valsartan (VALS, BCS class IV) from three oral-fixed combination products with hydrochlorothiazide (HCTZ, BCS class III) (Co-Diovan® Forte as reference and two generic formulations in development) by conducting in vivo predictive dissolution with a gastrointestinal simulator (GIS) and a physiologically based biopharmaceutic model (PBBM). In the first BE study, the HCTZ failed, but the VALS 90% CI of Cmax and the AUC were within the acceptance limits, while, in the second BE study, the HCTZ 90% CI of Cmax and the AUC were within the acceptance limits, but the VALS failed. As both drugs belong to different BCS classes, their limiting factors for absorption are different. On the other hand, the gastrointestinal variables affected by the formulation excipients have a distinct impact on their in vivo exposures. Dissolution tests of the three products were performed in a GIS, and a PBBM was constructed for VALS by incorporating in the mathematical model of the in vitro-in vivo correlation (IVIVC) the gastrointestinal variables affected by the excipients, namely, VALS permeability and GI transit time. VALS permeability in presence of the formulation excipients was characterized using the in situ perfusion method in rats, and the impact of the excipients on the GI transit times was estimated from the HCTZ's in vivo results. The model was able to fit the in vivo BE results with a good prediction error. This study contributes to the field by showing the usefulness of PBBM in establishing in vitro-in vivo relationships incorporating not only dissolution data but also other gastrointestinal critical variables that affect drug exposure in BCS class IV compounds.

Retinal Function in Long-Term Type 1 Diabetes without Retinopathy: Insights from Pattern Electroretinogram and Pattern Visual Evoked Potentials Assessments.

BACKGROUND: To evaluate changes in pattern electroretinogram (pERG) and pattern visual evoked potentials (pVEP) in patients with long-lasting type 1 diabetes without diabetic retinopathy (DR). METHODS: Prospective study involving 92 eyes divided into two groups. The diabetic group included 46 eyes of 23 patients with type 1 diabetes (T1DM); the control group included 23 age-matched healthy subjects. pERG and pVEP were assessed using the RETI-port/scan21 recording software (version 1021.3.0.0). RESULTS: Mean age was 48 ± 9.77 years for the diabetic group and 51.7 ± 4.75 years for the control group. The mean duration of diabetes was 28.88 ± 8.04 years. The mean HbA1c value was 7.29 ± 0.89%. There were no differences in the age or sex distribution. Regarding the pERG, T1DM patients exhibited a significant decrease in the amplitude of the P50 and N95 waves compared to the control group (p = 0.018 and p = 0.035, respectively), with no differences in the peak time of each component. pVEP showed no significant changes in either peak time or amplitude of the different components. CONCLUSIONS: Long-term T1DM patients without DR showed changes in the amplitude of pERG waves with preserved peak times. We did not observe modifications in pVEP. pERG may serve as a subclinical marker of ganglion cell damage in long-term T1DM patients.

Effectiveness of a Spectacle Lens with a Specific Asymmetric Myopic Peripheral Defocus: 12-Month Results in a Spanish Population.

BACKGROUND: Different designs of ophthalmic lenses have been studied to control the progression of myopia in children. This study aims to evaluate the short-term efficacy of a new design of ophthalmic lens with asymmetric myopic peripheral defocus (MPDL) on myopia progression in children compared to a control group wearing a single-vision lens (SVL). METHODS: Children aged 5 to 12 with myopia up to -0.50 D, astigmatism and anisometropia under 1.50 D, and corrected visual acuity over 20/20 were randomized to either the study group (MPDL) or control group (SVL). The myopia progression was evaluated by measuring axial length (AL) growth (IOL Master; Zeiss) over a period of one year. RESULTS: Ninety-two subjects were recruited. Forty-six children were randomly assigned to the control group, and 46 to the study group. In total, 83 children completed the clinical trial, with a mean age of 10.81 [9.53-11.92] years, among which 59.04% were female. After one year of treatment, there was less AL elongation in the study group compared to the control group (0.16 ± 0.16 mm vs. 0.24 ± 0.16 mm, p = 0.034). CONCLUSIONS: The MPDL significantly reduced the absolute growth of AL by 39% (p = 0.014) and relative growth of AL by 37.3% (p = 0.012) after 12 months in comparison to the control group in a Spanish population.

Electrophysiological findings in long-term type 1 diabetes patients without diabetic retinopathy using different ERG recording systems.

To assess full-field electroretinogram findings in long-term type 1 diabetes patients without diabetic retinopathy. Prospective study including 46 eyes of 23 patients with type 1 diabetes and 46 age-matched healthy eyes evaluated by the RETI-port/scan21 and the portable system RETeval following ISCEV guidelines. The average duration of diabetes was 28.88 ± 8.04 years. In scotopic conditions, using the RETI-port/scan21, diabetic patients showed an increase in b-wave implicit time (IT) (p = 0.017) with the lowest stimuli; a diminished b-wave amplitude (p = 0.005) in the mixed response, an increased IT (p = 0.004) with the high-intensity stimuli and an OP2 increased IT (p = 0.008) and decreased amplitude (p = 0.002). Under photopic conditions, b-wave amplitude was lower (p < 0.001) and 30-Hz flicker response was diminished (p = 0.021). Using the RETeval, in scotopic conditions, diabetic patients showed a reduction in the rod b-wave amplitude (p = 0.009), an increase in a-wave IT with the 280 Td.s stimulus (p = 0.005). OP2 had an increased IT and diminished amplitude (p = 0.003 and p = 0.002 respectively). 16 Td.s flicker showed an increased IT (p = 0.008) and diminished amplitude (p = 0.048). Despite variations in values between both systems, nearly all results displayed positive correlations. Long-term type 1 diabetes patients without diabetic retinopathy exhibit alterations in scotopic conditions, as evidenced by both conventional and portable electroretinogram devices. These findings suggest a modified retinal function, particularly in rod-driven pathways, even in the absence of vascular signs.

Muscle mass loss measured with portable ultrasound in hospitalized older adults: The ECOSARC study.

OBJECTIVES: The main objective was to analyze the evolution of muscle of the Quadriceps Rectus Femoris (QRF) between admission and discharge, in older adults hospitalized with an acute medical disease in Acute Geriatric Units (AGUs). DESIGN: Prospective multicentric observational cohort study. SETTING: Seven AGUs from University Hospitals in Spain. PARTICIPANTS: Hospitalized adults ≥ 70 years old, able to ambulate and without severe dementia. MEASUREMENTS: Ultrasound measurements of QRF were acquired at 2/3 distal between anterior-superior iliac spine and patella in both legs by trained Geriatricians. Ultrasound Chison model ECO2 was used. QRF area, thickness, edema, echogenicity, and fasciculations were measured. RESULTS: From the complete sample (n = 143), in 45 (31.5%) participants, ultrasound images were classified as non-valid by an expert radiologist. Mean age was 87.8 (SD 5.4). Mean hospital stay 7.6 days (SD 4.3). From those with valid images, 36 (49.3%), 2 (2.7%), and 35 (47.9%) presented a decrease, equal values, or an increase in QRF area from baseline to discharge, respectively, and 37 (50.0%), 2 (2.7%), and 35 (47.3%) presented a decrease, equal values, or an increase in QRF thickness, respectively. 26 (35.6%) presented a decrease in more than 0.2 cm2 of QRF area, and 23 (31.1%) a decrease in more than 0.1 cm of QRF thickness. Only 4 (5.4%) patients presented new edema, while 13 (17.6%) worsened echogenicity. CONCLUSION: One third of older adults develop significant muscle loss during a hospitalization for acute medical diseases. TRIAL REGISTRATION NUMBER: NCT05113758.

Towards precision medicine of long-acting aripiprazole through population pharmacokinetic modelling.

Population pharmacokinetic (popPK) models constitute a valuable tool for characterizing the pharmacokinetic properties of once-monthly long-acting injectable aripiprazole (LAI aripiprazole) and quantifying the sources of variability in drug exposure. Our aim is to develop a popPK model of both aripiprazole and its metabolite dehydro-aripiprazole in patients treated with LAI aripiprazole, and to personalize the dosing regimen of aripiprazole across different sub-groups of patients. This is a prospective study investigating the pharmacokinetics of LAI aripiprazole. A total of 93 patients were included, 21 for model development and 71 for external model evaluation. A one-compartment model with linear absorption and elimination adequately described both aripiprazole and dehydro-aripiprazole concentrations. The weight of the patients has been shown to be the factor that most influences the absorption. However, the metabolizing phenotype for CYP2D6 and the concomitant treatment with strong inhibitors of this cytochrome have been shown to be the covariates that most influence total drug exposure. This is the first popPK model developed for LAI aripiprazole that includes aripiprazole and its main active metabolite, dehydroaripiprazole. It provides a personalized dosage recommendation that maximizes the probability of achieving optimal therapeutic concentrations and minimizes the difficulties associated with trial-and-error therapeutic strategies carried out in clinical practice.

Seawater physics and chemistry along the Med-SHIP transects in the Mediterranean Sea in 2016.

The Mediterranean Sea has been sampled irregularly by research vessels in the past, mostly by national expeditions in regional waters. To monitor the hydrographic, biogeochemical and circulation changes in the Mediterranean Sea, a systematic repeat oceanographic survey programme called Med-SHIP was recommended by the Mediterranean Science Commission (CIESM) in 2011, as part of the Global Ocean Ship-based Hydrographic Investigations Program (GO-SHIP). Med-SHIP consists of zonal and meridional surveys with different frequencies, where comprehensive physical and biogeochemical properties are measured with the highest international standards. The first zonal survey was done in 2011 and repeated in 2018. In addition, a network of meridional (and other key) hydrographic sections were designed: the first cycle of these sections was completed in 2016, with three cruises funded by the EU project EUROFLEETS2. This paper presents the physical and chemical data of the meridional and key transects in the Western and Eastern Mediterranean Sea collected during those cruises.

Relación entre el estreñimiento y la calidad de vida de las personas en tratamiento renal sustitutivo con hemodiálisis / Relationship between constipation and the quality of life of individuals undergoing renal replacement therapy with hemodialysis

Introducción:El estreñimiento es un problema frecuente en pacientes en hemodiálisis, asociado, entre otros aspectos a comorbilidad, polimedicación y restricciones hídricas y dieté-ticas, pudiendo llegar a afectar la calidad de vida. Objetivos: Analizar la relación del estreñimiento en la calidad de vida de pacientes en hemodiálisis, determinar la prevalen-cia del estreñimiento objetivo y subjetivo, y analizar las varia-bles más influyentes. Material y Método: Estudio observacional descriptivo trans-versal en una unidad de hemodiálisis hospitalaria. Se emplea-ron los Criterios Diagnósticos Roma IV (2016) y escala visual Bristol para evaluar el estreñimiento. Para evaluar la calidad de vida, el cuestionario CVE-20. Resultados: Se estudiaron 38 pacientes (58% hombres) con una edad media de 68,69±12,76 años, tiempo en hemodiá-lisis de 44±37,19 meses y el 31,57% eran sedentarios. La ingesta hídrica diaria fue de 1004,05±460,13 ml y diuresis 658,11±696,47 ml. El índice de Charlson fue 8,15±2,29 pun-tos. El 45% presentaron estreñimiento subjetivo y 42% obje-tivo. Los pacientes con estreñimiento fueron: 56% mujeres, con edad media de 67,81±14,88 años y tiempo en hemodiá-lisis de 40,06±32,97 meses; 12% tenían pautados opioides, 44% quelantes del fósforo, 56% hierro intravenoso y 25% laxantes. La calidad de vida fue inferior en los pacientes es-treñidos (53,06 vs 69,62 puntos); existiendo diferencias signi-ficativas en todas las dimensiones del cuestionario.Conclusiones: En los pacientes en hemodiálisis existe una importante prevalencia de estreñimiento, siendo más pre-valente en mujeres. Este estreñimiento está asociado a peor percepción de la calidad de vida (AU)

Introducción: Constipation is a frequent issue in hemodialy-sis patients, associated, among other factors, with comorbidi-ty, polypharmacy, and restrictions in fluid and dietary intake, potentially affecting the quality of life.Objectives: To analyze the relationship between constipation and the quality of life of hemodialysis patients, determine the prevalence of objective and subjective constipation, and analyze the most influential variables.Material and Method: Cross-sectional descriptive obser-vational study in a hospital hemodialysis unit. The Rome IV Diagnostic Criteria (2016) and the Bristol Visual Scale were used to assess constipation. Quality of life was evaluated using the CVE-20 questionnaire.Results: A total of 38 patients were studied (58% males) with a mean age of 68.69±12.76 years, a hemodialysis du-ration of 44±37.19 months, and 31.57% were sedentary. aily fluid intake was 1004.05±460.13 ml, and diuresis was 658.11±696.47 ml. The Charlson index was 8.15±2.29 points. Subjective constipation was present in 45%, and ob-jective constipation in 42%. Patients with constipation were 56% females, with a mean age of 67.81±14.88 years, and hemodialysis duration of 40.06±32.97 months; 12% were prescribed opioids, 44% phosphorus binders, 56% intra-venous iron, and 24% laxatives. Quality of life was lower in constipated patients (53.06 vs. 69.62 points), with significant differences in all dimensions of the questionnaire.Conclusions: Hemodialysis patients have a significant preva-lence of constipation, more prevalent in females. This consti-pation is associated with a poorer perception of quality of life (AU)

Demographic, functional and clinical characteristics in hip fracture patients according to mental status of Spanish National Hip Fracture Registry.

OBJECTIVE: To describe the differences according to mental status at admission on the care process and 30-day outcomes in hip fracture patients, mainly regarding the use of rehabilitation resources and anti-osteoporotic medication, by analysing data from the Spanish National Hip Fracture Registry (RNFC, "Registro Nacional de Fracturas de Cadera" in Spanish). METHODS: We analysed prospectively collected data from a cohort of patients admitted participating in the Spanish National Hip Fracture Registry (RNFC) in 76 Spanish hospitals between 2017 and 2019. We classified participants using Short Portable Mental Status Questionnaire (SPMSQ), defining two groups: patients with ≤2 SPMSQ score and patients with >2 SPMSQ score. RESULTS: Of 21,254 patients was recorded SPMSQ in 17,242 patients, 9052 were >2 SPMSQ score (52.6%). These were older (87.7 vs. 85.3 years; p<0.001), had worse mobility (no-independent walking ability 26.0% vs. 4.5%; p<0.001) and were more likely to be living in nursing homes (35.3% vs. 9.6%; p<0.001). They were more likely to be treated nonoperatively (3.8% vs. 1.5%; p>0.001), less early mobilisation (57.5% vs. 68.9%; p<0.001) and suffered higher in-hospital mortality (5.2% vs. 2.7%; p<0.001). At discharge, they received less anti-osteoporotic medication (37.9% vs. 48.9%; p<0.001) and returned home less often (29.8%% vs. 51.2%; p<0.001). One month after fracture, patients with >2 SPMSQ score had poorer mobility (no-independent walking ability 44.4% vs. 24.9%; p<0.001) and were newly institutionalised in a nursing home more (12.6% vs. 12.0%; p<0.001) and were more likely to die by one-month post-fracture (9.5% vs. 4.6%; p<0.001). CONCLUSION: RNFC patients with >2 SPMSQ score were more vulnerable and had poorer outcomes than patients with ≤2 SPMSQ score, suggesting that they need specialised care in-hospital and in the recovery phase.

Predictors of fall risk in older adults using the G-STRIDE inertial sensor: an observational multicenter case-control study.

BACKGROUND: There are a lot of tools to use for fall assessment, but there is not yet one that predicts the risk of falls in the elderly. This study aims to evaluate the use of the G-STRIDE prototype in the analysis of fall risk, defining the cut-off points to predict the risk of falling and developing a predictive model that allows discriminating between subjects with and without fall risks and those at risk of future falls. METHODS: An observational, multicenter case-control study was conducted with older people coming from two different public hospitals and three different nursing homes. We gathered clinical variables ( Short Physical Performance Battery (SPPB), Standardized Frailty Criteria, Speed 4 m walk, Falls Efficacy Scale-International (FES-I), Time-Up Go Test, and Global Deterioration Scale (GDS)) and measured gait kinematics using an inertial measure unit (IMU). We performed a logistic regression model using a training set of observations (70% of the participants) to predict the probability of falls. RESULTS: A total of 163 participants were included, 86 people with gait and balance disorders or falls and 77 without falls; 67,8% were females, with a mean age of 82,63 ± 6,01 years. G-STRIDE made it possible to measure gait parameters under normal living conditions. There are 46 cut-off values of conventional clinical parameters and those estimated with the G-STRIDE solution. A logistic regression mixed model, with four conventional and 2 kinematic variables allows us to identify people at risk of falls showing good predictive value with AUC of 77,6% (sensitivity 0,773 y specificity 0,780). In addition, we could predict the fallers in the test group (30% observations not in the model) with similar performance to conventional methods. CONCLUSIONS: The G-STRIDE IMU device allows to predict the risk of falls using a mixed model with an accuracy of 0,776 with similar performance to conventional model. This approach allows better precision, low cost and less infrastructures for an early intervention and prevention of future falls.

Intranasal administration of molecular-gated mesoporous nanoparticles to increase ponatinib delivery to the brain.

Background: Glioblastoma is the most common and lethal brain cancer. New treatments are needed. However, the presence of the blood-brain barrier is limiting the development of new treatments directed toward the brain, as it restricts the access and distribution of drugs to the CNS. Materials & methods: In this work, two different nanoparticles (i.e., mesoporous silica nanoparticles and magnetic mesoporous silica nanoparticles) loaded with ponatinib were prepared. Results & conclusion: Both particles were characterized and tested in vitro and in vivo, proving that they are not toxic for blood-brain barrier cells and they increase the amount of drug reaching the brain when administered intranasally in comparison with the results obtained for the free drug.

This article presents a couple of promising nanoparticles for the treatment of brain cancer. This research is interesting because the brain and spinal cord are protected by a membrane that prevents toxic substances from reaching them but also hinders the access of drugs. One type of particle has a magnet in its core, so it can be driven with another external magnet until it reaches target; the other type does not have a magnet but has a small size, which would allow it to cross the membrane mentioned above. These particles have been proven to be able to kill cancer cells and to reach the brain after been administered through the nose in a better way than the free drug.

Vitamin D deficiency and SARS­CoV­2 infection: A retrospective case-Control study with big-data analysis covering March 2020 to March 2021.

BACKGROUND: Vitamin D may have immunomodulatory functions, and might therefore play a role in the pathogenesis of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, no conclusive evidence exists regarding its impact on the prevalence of this infection, the associated course of disease, or prognosis. OBJECTIVE: To study the association between SARS-CoV-2 infection and vitamin D deficiency in patients attending a tertiary university hospital, and to examine the clinical course of infection and prognosis for these patients. METHODS: This non-interventional, retrospective study, which involved big-data analysis and employed artificial intelligence to capture data from free text in the electronic health records of patients diagnosed with SARS-CoV-2, was undertaken at a tertiary university hospital in Madrid, Spain, between March 2020 and March 2021. The variables recorded were vitamin D deficiency, sociodemographic and clinical characteristics, course of disease, and prognosis. RESULTS: Of the 143,157 patients analysed, 36,261 had SARS-CoV-2 infection (25.33%) during the study period, among whom 2,588 (7.14%) had a vitamin D deficiency. Among these latter patients, women (OR 1.45 [95%CI 1.33-1.57]), adults over 80 years of age (OR 2.63 [95%CI 2.38-2.91]), people living in nursing homes (OR 2.88 [95%CI 2.95-3.45]), and patients with walking dependence (OR 3.45 [95%CI 2.85-4.26]) appeared in higher proportion. After adjusting for confounding factors, a higher proportion of subjects with SARS-CoV-2 plus vitamin D deficiency required hospitalisation (OR 1.38 [95%CI 1.26-1.51]), and had a longer mean hospital stay (3.94 compared to 2.19 days in those with normal levels; P = 0.02). CONCLUSION: A low serum 25(OH) vitamin D concentration in patients with SARS-CoV-2 infection is significantly associated with a greater risk of hospitalisation and a longer hospital stay. Among such patients, higher proportions of institutionalised and dependent people over 80 years of age were detected.

A database with frailty, functional and inertial gait metrics for the research of fall causes in older adults.

The GSTRIDE database contains information of the health status assessment of 163 elderly adults. We provide socio-demographic data, functional and frailty variables, and the outcomes from tests commonly performed for the evaluation of elder people. The database contains gait parameters estimated from the measurements of an Inertial Measurement Unit (IMU) placed on the foot of volunteers. These parameters include the total walking distance, the number of strides and multiple spatio-temporal gait parameters, such as stride length, stride time, speed, foot angles and clearance, among others. The main processed database is stored, apart from MS Excel, in CSV format to ensure their usability. The database is complemented with the raw IMU recordings in TXT format, in order to let researchers test other algorithms of gait analysis. We include the Python programming codes as a base to reproduce or modify them. The database stores data to study the frailty-related parameters that distinguish faller and non-faller populations, and analyze the gait-related parameters in the frail subjects, which are essential topics for the elderly.

Assessing falls in the elderly population using G-STRIDE foot-mounted inertial sensor.

Falls are one of the main concerns in the elderly population due to their high prevalence and associated consequences. Guidelines for the management of the elder with falls are comprised of multidimensional assessments, especially gait and balance. Daily clinical practice needs for timely, effortless, and precise tools to assess gait. This work presents the clinical validation of the G-STRIDE system, a 6-axis inertial measurement unit (IMU) with onboard processing algorithms, that allows the calculation of walking-related metrics correlated with clinical markers of fall risk. A cross-sectional case-control study was conducted with 163 participants (falls and non-falls groups). All volunteers were assessed with clinical scales and conducted a 15-min walking test at a self-selected pace while wearing the G-STRIDE. G-STRIDE is a low-cost solution to facilitate the transfer to society and clinical evaluations. It is open hardware and flexible and, thus, has the advantage of providing runtime data processing. Walking descriptors were derived from the device, and a correlation analysis was conducted between walking and clinical variables. G-STRIDE allowed measuring walking parameters in non-restricted walking conditions (e.g. hallway). Walking parameters statistically discriminate between falls and non-falls groups. We found good/excellent estimation accuracy (ICC = 0.885; [Formula: see text]) for walking speed, showing good/excellent correlation between gait speed and several clinical variables. G-STRIDE can calculate walking-related metrics that allow for discrimination between falls and non-falls groups, which correlates with clinical indicators of fall risk. A preliminary fall-risk assessment based on the walking parameters was found to improve the Timed Up and Go test in the identification of fallers.

Specialized Care Resources for Diagnosis and Management of Patients Who Have Suffered Falls: Results of a National Survey in Geriatric Units.

INTRODUCTION: Clinical guidelines recommend comprehensive multifactorial assessment and intervention to prevent falls and fractures in older populations. METHODS: A descriptive study was conducted by the Falls Study Group of the Spanish Geriatric Medicine Society (SEMEG) to outline which types of healthcare-specific resources were assigned for fall assessment in Spanish geriatric departments. A self-reported seven-item questionnaire was delivered from February 2019 to February 2020. Where geriatric medicine departments were not available, we tried to contact geriatricians working in those areas. RESULTS: Information was obtained regarding 91 participant centers from 15 autonomous communities, 35.1% being from Catalonia and 20.8% from Madrid. A total of 21.6% reported a multidisciplinary falls unit, half of them in geriatric day hospitals. Half of them reported fall assessment as part of a general geriatric assessment in general geriatric outpatient clinics (49.5%) and, in 74.7% of cases, the assessment was based on functional tests. A total of 18.7% reported the use of biomechanical tools, such as posturography, gait-rides or accelerometers, for gait and balance analysis, and 5.5% used dual X-ray absorptiometry. A total of 34% reported research activity focused on falls or related areas. Regarding intervention strategies, 59% reported in-hospital exercise programs focused on gait and balance improvement and 79% were aware of community programs or the pathways to refer patients to these resources. CONCLUSIONS: This study provides a necessary starting point for a future deep analysis. Although this study was carried out in Spain, it highlights the need to improve public health in the field of fall prevention, as well as the need, when implementing public health measures, to verify that these measures are implemented homogeneously throughout the territory. Therefore, although this analysis was at the local level, it could be useful for other countries to reproduce the model.

Deregulation of the miR-19b/PPP2R5E Signaling Axis Shows High Functional Impact in Colorectal Cancer Cells.

MicroRNA (miR)-19b is deregulated in colorectal cancer (CRC) and locally advanced rectal cancer (LARC), predicting worse outcome and disease progression in CRC patients, and acting as a promising prognostic marker of patient recurrence and pathological response to 5-fluorouracil (5-FU)-based neoadjuvant chemoradiotherapy in LARC. Moreover, there is a strong inverse correlation between miR-19b and PPP2R5E in LARC, and both predict the response to neoadjuvant therapy in LARC patients. However, the functional role of the miR-19b/PPP2R5E axis in CRC cells remains to be experimentally evaluated. Here, we confirm with luciferase assays that miR-19b is a direct negative regulator of PPP2R5E in CRC, which is concordant with the observed decreased PP2A activity levels after miR-19b overexpression. Furthermore, PPP2R5E downregulation plays a key role mediating miR-19b-induced oncogenic effects, increasing cell viability, colonosphere formation ability, and the migration of CRC cells. Lastly, we also confirm the role of miR-19b mediating 5-FU sensitivity of CRC cells through negative PPP2R5E regulation. Altogether, our findings demonstrate the functional relevance of the miR-19b/PPP2R5E signaling pathway in disease progression, and its potential therapeutic value determining the 5-FU response of CRC cells.

Establishment and Validation of a New Co-Culture for the Evaluation of the Permeability through the Blood-Brain Barrier in Patients with Glioblastoma.

Currently, the mechanisms involved in drug access to the central nervous system (CNS) are not completely elucidated, and research efforts to understand the behaviour of the therapeutic agents to access the blood-brain barrier continue with the utmost importance. The aim of this work was the creation and validation of a new in vitro model capable of predicting the in vivo permeability across the blood-brain barrier in the presence of glioblastoma. The selected in vitro method was a cell co-culture model of epithelial cell lines (MDCK and MDCK-MDR1) with a glioblastoma cell line (U87-MG). Several drugs were tested (letrozole, gemcitabine, methotrexate and ganciclovir). Comparison of the proposed in vitro model, MDCK and MDCK-MDR1 co-cultured with U87-MG, and in vivo studies showed a great predictability for each cell line, with R2 values of 0.8917 and 0.8296, respectively. Therefore, both cells lines (MDCK and MDCK-MDR1) are valid for predicting the access of drugs to the CNS in the presence of glioblastoma.

"SARCOPENIA MEASURED BY ULTRASOUND IN HOSPITALIZED OLDER ADULTS" (ECOSARC): multi-centre, prospective observational study protocol.

BACKGROUND: Measurement of muscle mass and function, and thereafter, screening and diagnosis of sarcopenia, is a challenge and a need in hospitalized older adults. However, it is difficult in complex real-world old patients, because usually they are unable to collaborate with clinical, functional, and imaging testing. Ultrasound measurement of quadriceps rectus femoris (QRF) provides a non-invasive, real-time assessment of muscle quantity and quality, and is highly acceptable to participants with excellent inter-rater and intra-rater variability. However, normative data, protocol standardization, and association with longitudinal outcomes, needs further research and consensus. METHODS: Prospective exploratory multicenter study in older adults admitted to Acute Geriatric Units (AGUs) for medical reasons. 157 subjects from 7 AGUs of Spain were recruited between May 2019 and January 2022. Muscle ultrasound measurements of the anterior vastus of the QRF were acquired on admission and on discharge, using a previously validated protocol, using a Chieson model ECO2 ultrasound system (Chieson Medical Technologies, Co. Ltd, Wimxu District Wuxi, Jiangsu, China). Measurements included the cross-sectional area, muscle thickness in longitudinal view, intramuscular central tendon thickness, echogenicity, and the presence or absence of edema and fasciculations. Functional, nutritional, and DXA measurements were provided. Clinical follow-up was completed at discharge, and 30 and 90 days after discharge. Variations between hospital admission and discharge ultrasound values, and the relationship with clinical variables, will be analyzed using paired t-tests, Wilcoxon tests, or Mc Nemar chi-square tests when necessary. Prevalence of sarcopenia will be calculated, as well as sensitivity and specificity of ultrasound measurements to determine sarcopenia. Kappa analysis will be used to analyze the concordance between measurements, and sensitivity analysis will be conducted for each participating center. DISCUSSION: The results obtained will be of great interest to the scientific geriatric community to assess the utility and validity of ultrasound measurements for the detection and follow-up of sarcopenia in hospitalized older adults, and its association with adverse outcomes. TRIAL REGISTRATION: NCT05113758. Registration date: November 9th 2021. Retrospectively registered.

Access to the CNS: Strategies to overcome the BBB.

The blood-brain barrier (BBB) limits the access of substances to the central nervous system (CNS) which hinders the treatment of pathologies affecting the brain and the spinal cord. Nowadays, research is focus on new strategies to overcome the BBB and can treat the pathologies affecting the CNS are needed. In this review, the different strategies that allow and increase the access of substances to the CNS are analysed and extended commented, not only invasive strategies but also non-invasive ones. The invasive techniques include the direct injection into the brain parenchyma or the CSF and the therapeutic opening of the BBB, while the non-invasive techniques include the use of alternative routes of administration (nose-to-brain route), the inhibition of efflux transporters (as it is important to prevent the drug efflux from the brain and enhance the therapeutic efficiency), the chemical modification of the molecules (prodrugs and chemical drug delivery systems (CDDS)) and the use of nanocarriers. In the future, knowledge about nanocarriers to treat CNS diseases will continue to increase, but the use of other strategies such as drug repurposing or drug reprofiling, which are cheaper and less time consuming, may limit its transfer to society. The main conclusion is that the combination of different strategies may be the most interesting approach to increase the access of substances to the CNS.