Asia-Pacific consensus on long-term and sequential therapy for osteoporosis.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition. The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and antiresorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to antiresorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for individuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions: This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Adapting response to a measles outbreak in a context of high vaccination and breakthrough cases: an example from Vaud, Switzerland, January to March 2024.

A measles outbreak with 51 cases occurred in the canton of Vaud, Switzerland, between January and March 2024. The outbreak was triggered by an imported case, and 37 (72.5%) subsequent cases were previously vaccinated individuals. Epidemiological investigations showed that vaccinated measles cases were symptomatic and infectious. In a highly vaccinated population, it is important to raise awareness among healthcare professionals to suspect and test for measles virus when an outbreak is declared, irrespective of the vaccination status of the patients.

Beyond VEGF: Angiopoietin-Tie Signaling Pathway in Diabetic Retinopathy.

Complications from diabetic retinopathy such as diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) constitute leading causes of preventable vision loss in working-age patients. Since vascular endothelial growth factor (VEGF) plays a major role in the pathogenesis of these complications, VEGF inhibitors have been the cornerstone of their treatment. Anti-VEGF monotherapy is an effective but burdensome treatment for DME. However, due to the intensive and burdensome treatment, most patients in routine clinical practice are undertreated, and therefore, their outcomes are compromised. Even in adequately treated patients, persistent DME is reported anywhere from 30% to 60% depending on the drug used. PDR is currently treated by anti-VEGF, panretinal photocoagulation (PRP) or a combination of both. Similarly, a number of eyes, despite these treatments, continue to progress to tractional retinal detachment and vitreous hemorrhage. Clearly there are other molecular pathways other than VEGF involved in the pathogenesis of DME and PDR. One of these pathways is the angiopoietin-Tie signaling pathway. Angiopoietin 1 (Ang1) plays a major role in maintaining vascular quiescence and stability. It acts as a molecular brake against vascular destabilization and inflammation that is usually promoted by angiopoietin 2 (Ang2). Several pathological conditions including chronic hyperglycemia lead to Ang2 upregulation. Recent regulatory approval of the bi-specific antibody, faricimab, may improve long term outcomes in DME. It targets both the Ang/Tie and VEGF pathways. The YOSEMITE and RHINE were multicenter, double-masked, randomized non-inferiority phase 3 clinical trials that compared faricimab to aflibercept in eyes with center-involved DME. At 12 months of follow-up, faricimab demonstrated non-inferior vision gains, improved anatomic outcomes and a potential for extended dosing when compared to aflibercept. The 2-year results of the YOSEMITE and RHINE trials demonstrated that the anatomic and functional results obtained at the 1 year follow-up were maintained. Short term outcomes of previously treated and treatment-naive eyes with DME that were treated with faricimab during routine clinical practice suggest a beneficial effect of faricimab over other agents. Targeting of Ang2 has been reported by several other means including VE-PTP inhibitors, integrin binding peptide and surrobodies.

Feasibility and Short-Term Outcomes in Liver-First Approach: A Spanish Snapshot Study (the RENACI Project).

(1) Background: The liver-first approach may be indicated for colorectal cancer patients with synchronous liver metastases to whom preoperative chemotherapy opens a potential window in which liver resection may be undertaken. This study aims to present the data of feasibility and short-term outcomes in the liver-first approach. (2) Methods: A prospective observational study was performed in Spanish hospitals that had a medium/high-volume of HPB surgeries from 1 June 2019 to 31 August 2020. (3) Results: In total, 40 hospitals participated, including a total of 2288 hepatectomies, 1350 for colorectal liver metastases, 150 of them (11.1%) using the liver-first approach, 63 (42.0%) in hospitals performing <50 hepatectomies/year. The proportion of patients as ASA III was significantly higher in centers performing ≥50 hepatectomies/year (difference: 18.9%; p = 0.0213). In 81.1% of the cases, the primary tumor was in the rectum or sigmoid colon. In total, 40% of the patients underwent major hepatectomies. The surgical approach was open surgery in 87 (58.0%) patients. Resection margins were R0 in 78.5% of the patients. In total, 40 (26.7%) patients had complications after the liver resection and 36 (27.3%) had complications after the primary resection. One-hundred and thirty-two (89.3%) patients completed the therapeutic regime. (4) Conclusions: There were no differences in the surgical outcomes between the centers performing <50 and ≥50 hepatectomies/year. Further analysis evaluating factors associated with clinical outcomes and determining the best candidates for this approach will be subsequently conducted.

Modulation of neuronal dynamics by sustained and activity-dependent continuous-wave near-infrared laser stimulation.

Significance: Near-infrared laser illumination is a non-invasive alternative/complement to classical stimulation methods in neuroscience but the mechanisms underlying its action on neuronal dynamics remain unclear. Most studies deal with high-frequency pulsed protocols and stationary characterizations disregarding the dynamic modulatory effect of sustained and activity-dependent stimulation. The understanding of such modulation and its widespread dissemination can help to develop specific interventions for research applications and treatments for neural disorders. Aim: We quantified the effect of continuous-wave near-infrared (CW-NIR) laser illumination on single neuron dynamics using sustained stimulation and an open-source activity-dependent protocol to identify the biophysical mechanisms underlying this modulation and its time course. Approach: We characterized the effect by simultaneously performing long intracellular recordings of membrane potential while delivering sustained and closed-loop CW-NIR laser stimulation. We used waveform metrics and conductance-based models to assess the role of specific biophysical candidates on the modulation. Results: We show that CW-NIR sustained illumination asymmetrically accelerates action potential dynamics and the spiking rate on single neurons, while closed-loop stimulation unveils its action at different phases of the neuron dynamics. Our model study points out the action of CW-NIR on specific ionic-channels and the key role of temperature on channel properties to explain the modulatory effect. Conclusions: Both sustained and activity-dependent CW-NIR stimulation effectively modulate neuronal dynamics by a combination of biophysical mechanisms. Our open-source protocols can help to disseminate this non-invasive optical stimulation in novel research and clinical applications.

Enhancing motor functional recovery in spinal cord injury through pharmacological inhibition of Dickkopf-1 with BHQ880 antibody.

BACKGROUND: Mounting experimental evidence has underscored the remarkable role played by the Wnt family of proteins in the spinal cord functioning and therapeutic potential in spinal cord injury (SCI). We aim to provide a therapeutic prospect associated with the modulation of canonical Wnt signaling, examining the spatio-temporal expression pattern of Dickkopf-1 (Dkk1) and its neutralization after SCI. We employ an intraparenchymal injection of the clinically validated Dkk1-blocking antibody, BHQ880, to elucidate its effects in SCI. METHODS: A rat model of contusion SCI was used. Histological analyses were performed, wherein Dkk1 protein was sought, and ELISA analyses were employed for Dkk1 detection in cerebrospinal fluid and serum. To ascertain the BHQ880 therapeutic effect, rats were subjected to SCI and then injected with the antibody in the lesion epicenter 24 hours post-injury (hpi). Subsequent evaluation of motor functional recovery extended up to 56 days post-injury (dpi). qRT-PCR and histological analyses were conducted. RESULTS: We demonstrate the presence of Dkk1 in the healthy rat spinal cord, with pronounced alterations observed following injury, primarily concentrated in the epicenter regions. Notably, a significative upregulation of Dkk1 was detected at 24 hpi, peaking at 3 dpi and remaining elevated until 42 dpi. Moreover, we revealed that early administration of BHQ880 considerably improved motor functional recovery, promoted preservation of myelinated tissue, and reduced astroglial and microglia/macrophage reactivity. Furthermore, there was a decrease in the acute expression of different inflammatory genes. CONCLUSIONS: Collectively, our findings highlight the therapeutic potential of BHQ880 treatment in the context of SCI.

Long-term risk of death in patients with infection attended by prehospital emergency services. / Modelo de riesgo de mortalidad a largo plazo en pacientes con infección atendidos por servicios de emergencias prehospitalarios.

OBJECTIVES: To develop and validate a risk model for 1-year mortality based on variables available from early prehospital emergency attendance of patients with infection. MATERIAL AND METHODS: Prospective, observational, noninterventional multicenter study in adults with suspected infection transferred to 4 Spanish hospitals by advanced life-support ambulances from June 1, 2020, through June 30, 2022. We collected demographic, physiological, clinical, and analytical data. Cox regression analysis was used to develop and validate a risk model for 1-year mortality. RESULTS: Four hundred ten patients were enrolled (development cohort, 287; validation cohort, 123). Cumulative mortality was 49% overall. Sepsis (infection plus a Sepsis-related Organ Failure Assessment score of 2 or higher) was diagnosed in 29.2% of survivors vs 56.7% of nonsurvivors. The risk model achieved an area under the receiver operating characteristic curve of 0.89 for 1-year mortality. The following predictors were included in the model: age; institutionalization; age-adjusted Charlson comorbidity index; PaCO2; potassium, lactate, urea nitrogen, and creatinine levels; fraction of inspired oxygen; and diagnosed sepsis. CONCLUSION: The model showed excellent ability to predict 1-year mortality based on epidemiological, analytical, and clinical variables, identifying patients at high risk of death soon after their first contact with the health care system.

OBJETIVO: Diseñar y validar un modelo de riesgo con variables determinadas a nivel prehospitalario para predecir el riesgo de mortalidad a largo plazo (1 año) en pacientes con infección. METODO: Estudio multicéntrico, observacional prospectivo, sin intervención, en pacientes adultos con sospecha infección atendidos por unidades de soporte vital avanzado y trasladados a 4 hospitales españoles entre el 1 de junio de 2020 y el 30 de junio de 2022. Se recogieron variables demográficas, fisiológicas, clínicas y analíticas. Se construyó y validó un modelo de riesgo para la mortalidad a un año usando una regresión de Cox. RESULTADOS: Se incluyeron 410 pacientes, con una tasa de mortalidad acumulada al año del 49%. La tasa de diagnóstico de sepsis (infección e incremento sobre el SOFA basal $ 2 puntos) fue del 29,2% en supervivientes frente a un 56,7% en no supervivientes. El modelo predictivo obtuvo un área bajo la curva de la característica operativa del receptor para la mortalidad a un año fue de 0,89, e incluyó: edad, institucionalización, índice de comorbilidad de Charlson ajustado por edad, presión parcial de dióxido de carbono, potasio, lactato, nitrógeno ureico en sangre, creatinina, saturación en relación con fracción inspirada de oxígeno y diagnóstico de sepsis. CONCLUSIONES: El modelo desarrollado con variables epidemiológicas, analíticas y clínicas mostró una excelente capacidad predictiva, y permitió identificar desde el primer contacto del paciente con el sistema sanitario, a modo de evento centinela, casos de alto riesgo.

Study of Salmonella spp. from Cage Papers Belonging to Pet Birds in an Argentinean Canary Breeder Championship.

Birds, including canaries and other birds, have become increasingly popular as pets. Bird fairs, where breeders gather and show their production in a championship setting, present a setting for possible Salmonella spp. contamination and transmission. Therefore, this study estimated the rate of Salmonella spp. isolation from cage papers, located in the bottom of cages of exotic pet birds, including canaries. Collected Salmonella isolates were used to determine the antimicrobial resistance profile to 52 antibiotics and 17 commercial disinfectants, based on pure or a mixture of acids, alcohols, aldehydes, alkalis, halogens, peroxygen, and quaternary ammonium compounds. The samples consisted of 774 cage papers taken in the 2015 Argentinean canary breeder championship, pooling three cage papers into one sterile sampling bag. Only one pool of the cage papers was positive for Salmonella spp. (0.4%), which belonged to the sample from three frill canary cages. Two strains of Salmonella serotype Glostrup were isolated, which were only resistant to sulfonamides and erythromycin and sensitive to alkali-based product PL301 AS. Although the rate of Salmonella spp. isolation from cage papers in an Argentinean canary breeder championship is low, it should not be discounted because Salmonella ser. Glostrup can be a source of human Salmonella outbreaks and they show high resistance to disinfecting products.

Analysis of Protection and Immune Response against Teladorsagia circumcincta in Goats Immunised with Thiol-Binding Proteins from Adult Worms.

In view of the increasing occurrence of anthelmintic-resistant strains of gastrointestinal nematodes in ruminants, various alternative control strategies have been investigated, such as those based on the induction of protective immune responses by immunisation with parasite antigens. In this study, the protective activity of somatic antigens from adult worms of Teladorsagia circumcincta purified by affinity chromatography on thiol-sepharose was analysed in goats. After challenge, the enriched products induced a slight reduction in the cumulative faecal egg counts (21%) and in the number of worms (23.3%), with a greater effect on female worms, which also showed a reduction in parameters related to their fertility. These parasitological findings were associated with a Th2 immune response, with a prominent local humoral response and an eosinophilic infiltrate in the gastric mucosa (negatively associated with the fertility of female worms and the number of worms, respectively), as well as an infiltration of MCHII+, CD4+, IgG+ and IgA+ cells. However, several analyses showed an increase in CD8+ cells in the mucosa, as well as IL-2 expression in the gastric lymph nodes, which may have been associated with inhibition of protective responses or with the development of mixed Th1/Th2 responses, a finding that should be analysed in future studies.

Screening of Microalgae for Bioactivity with Antiviral, Antibacterial, Anti-Inflammatory and Anti-Cancer Assays.

Marine microalgae are a rich reservoir of natural compounds, including bioactives. Nonetheless, these organisms remain fairly unexplored despite their potential biotechnological applications. Culture collections with diverse taxonomic groups and lifestyles are a good source to unlock this potential and discover new molecules for multiple applications such as the treatment of human pathologies or the production of aquaculture species. In the present work extracts from thirty-three strains (including twenty dinoflagellates, four diatoms and nine strains from seven other algal classes), cultivated under identical conditions, were examined for their antiviral, antibacterial, anti-inflammatory and anti-cancer activities. Among these, antiviral and anti-inflammatory activities were detected in a few strains while the antibacterial tests showed positive results in most assays. In turn, most trials did not show any anti-cancer activity. Significant differences were observed between species within the same class, in particular dinoflagellates, which were better represented in this study. These preliminary findings pave the way for an in-depth characterization of the extracts with highest signals in each test, the identification of the compounds responsible for the biological activities found and a further screening of the CCVIEO culture collection.

Spanish vs USA cohort comparison of prehospital trauma scores to predict short-term mortality.

BACKGROUND: This study aimed to evaluate three prehospital early warning scores (EWSs): RTS, MGAP and MREMS, to predict short-term mortality in acute life-threatening trauma and injury/illness by comparing United States (US) and Spanish cohorts. METHODS: A total of 8,854 patients, 8,598/256 survivors/nonsurvivors, comprised the unified cohort. Datasets were randomly divided into training and test sets. Training sets were used to analyse the discriminative power of the scores in terms of the area under the curve (AUC), and the score performance was assessed in the test set in terms of sensitivity (SE), specificity (SP), accuracy (ACC) and balanced accuracy (BAC). RESULTS: The three scores showed great discriminative power with AUCs>0.90, and no significant differences between cohorts were found. In the test set, RTS/MREMS/MGAP showed SE/SP/ACC/BAC values of 86.0/89.9/89.6/87.1%, 91.0/86.9/87.5/88.5%, and 87.7/82.9/83.4/85.2%, respectively. CONCLUSIONS: All EWSs showed excellent ability to predict the risk of short-term mortality, independent of the country.

Human olfactory neural progenitor cells reveal differences in IL-6, IL-8, thrombospondin-1, and MCP-1 in major depression disorder and borderline personality disorder.

Background: Discovering biological markers is essential for understanding and treating mental disorders. Despite the limitations of current non-invasive methods, neural progenitor cells from the olfactory epithelium (hNPCs-OE) have been emphasized as potential biomarker sources. This study measured soluble factors in these cells in Major Depressive Disorder (MDD), Borderline Personality Disorder (BPD), and healthy controls (HC). Methods: We assessed thirty-five participants divided into MDD (n=14), BPD (n=14), and HC (n=7). MDD was assessed using the Hamilton Depression Rating Scale. BPD was evaluated using the DSM-5 criteria and the Structured Clinical Interview for Personality Disorders. We isolated hNPCs-OE, collected intracellular proteins and conditioned medium, and quantified markers and soluble factors, including Interleukin-6, interleukin-8, and others. Analysis was conducted using one-way ANOVA or Kruskal-Wallis test and linear regression. Results: We found that hNPCs-OE of MDD and BPD decreased Sox2 and laminin receptor-67 kDa levels. MASH-1 decreased in BPD, while tubulin beta-III decreased in MDD compared to controls and BPD. Also, we found significant differences in IL-6, IL-8, MCP-1, and thrombospondin-1 levels between controls and MDD, or BPD, but not between MDD and BPD. Conclusions: Altered protein markers are evident in the nhNPCs-OE in MDD and BPD patients. These cells also secrete higher concentrations of inflammatory cytokines than HC cells. The results suggest the potential utility of hNPCs-OE as an in vitro model for researching biological protein markers in psychiatric disorders. However, more extensive validation studies are needed to confirm their effectiveness and specificity in neuropsychiatric disorders.

Response of the toxic dinoflagellate Alexandrium minutum to exudates of the eelgrass Zostera marina.

Biotic interactions are a key factor in the development of harmful algal blooms. Recently, a lower abundance of planktonic dinoflagellates has been reported in areas dominated by seagrass beds, suggesting a negative interaction between both groups of organisms. The interaction between planktonic dinoflagellates and marine phanerogams, as well as the way in which bacteria can affect this interaction, was studied in two experiments using a non-axenic culture of the toxic dinoflagellate Alexandrium minutum exposed to increasing additions of eelgrass (Zostera marina) exudates from old and young leaves and to the presence or absence of antibiotics. In these experiments, A. minutum abundance, growth rate and photosynthetic efficiency (Fv/Fm), as well as bacterial abundance, were measured every 48 h. Toxin concentration per cell was determined at the end of both experiments. Our results demonstrated that Z. marina exudates reduced A. minutum growth rate and, in one of the experiments, also the photosynthetic efficiency. These results are not an indirect effect mediated by the bacteria in the culture, although their growth modify the magnitude of the negative impact on the dinoflagellate growth rate. No clear pattern was observed in the variation of toxin production with the treatments.

Utility of non-invasive monitoring of exhaled carbon dioxide and perfusion index in adult patients in the emergency department.

BACKGROUND: Several noninvasive solutions are available for the assessment of patients at risk of deterioration. Capnography, in the form of end-tidal exhaled CO2 (ETCO2) and perfusion index (PI), could provide relevant information about patient prognosis. The aim of the present project was to determine the association of ETCO2 and PI with mortality of patients admitted to the emergency department (ED). METHODS: Multicenter, prospective, cohort study of adult patients with acute disease who needed continuous monitoring in the ED. The study included two tertiary hospitals in Spain between October 2022 and June 2023. The primary outcome of the study was in-hospital mortality (all-cause). Demographics, vital signs, ETCO2 and PI were collected. RESULTS: A total of 687 patients were included in the study. The in-hospital mortality rate was 6.8%. The median age was 79 years (IQR: 69-86), and 63.3% were males. The median ETCO2 value was 30 mmHg (26-35) in survivors and 23 mmHg (16-30) in nonsurvivors (p = 0.001). For the PI, the medians were 4.7% (2.8-8.1) for survivors and 2.5% (0.98-4-4) for nonsurvivors (p < 0.001). The model that presented the best AUC was age (odds ratio (OR): 1.02 (1.00-1.05)), the respiratory rate (OR: 1.06 (1.02-1.11)), and the PI (OR: 0.83 (0.75-0.91)), with a result of 0.840 (95% CI: 0.795-0.886); the model with the respiratory rate (OR: 1.05 (1.01-1.10)), the PI (OR: 0.84 (0.76-0.93)), and the ETCO2 (no statistically significant OR), with an AUC of 0.838 (95% CI: 0.787-0.889). CONCLUSIONS: The present study showed that the PI and respiratory rate are independently associated with in-hospital mortality. Both the PI and ETCO2 are predictive parameters with improved prognostic performance compared with that of standard vital signs.

GrimAge is elevated in older adults with mild COVID-19 an exploratory analysis.

COVID-19 has been contained; however, the side effects associated with its infection continue to be a challenge for public health, particularly for older adults. On the other hand, epigenetic status contributes to the inter-individual health status and is associated with COVID-19 severity. Nevertheless, current studies focus only on severe COVID-19. Considering that most of the worldwide population developed mild COVID-19 infection. In the present exploratory study, we aim to analyze the association of mild COVID-19 with epigenetic ages (HorvathAge, HannumAge, GrimAge, PhenoAge, SkinAge, and DNAmTL) and clinical variables obtained from a Mexican cohort of older adults. We found that all epigenetic ages significantly differ from the chronological age, but only GrimAge is elevated. Additionally, both the intrinsic epigenetic age acceleration (IEAA) and the extrinsic epigenetic age acceleration (EEAA) are accelerated in all patients. Moreover, we found that immunological estimators and DNA damage were associated with PhenoAge, SkinBloodHorvathAge, and HorvathAge, suggesting that the effects of mild COVID-19 on the epigenetic clocks are mainly associated with inflammation and immunology changes. In conclusion, our results show that the effects of mild COVID-19 on the epigenetic clock are mainly associated with the immune system and an increase in GrimAge, IEAA, and EEAA.

Comparison of eight prehospital early warning scores in life-threatening acute respiratory distress: a prospective, observational, multicentre, ambulance-based, external validation study.

BACKGROUND: A myriad of early warning scores (EWSs) exist, yet there is a need to identify the most clinically valid score to be used in prehospital respiratory assessments to estimate short-term and midterm mortality, intensive-care unit admission, and airway management in life-threatening acute respiratory distress. METHODS: This is a prospective, observational, multicentre, ambulance-based, external validation study performed in 44 ambulance services and four hospitals across three Spanish provinces (ie, Salamanca, Segovia, and Valladolid). We identified adults (ie, those aged 18 years and older) discharged to the emergency department with suspected acute respiratory distress. The primary outcome was 2-day all-cause in-hospital mortality, for all the patients or according to prehospital respiratory conditions, including dyspnoea, chronic obstructive pulmonary disease (COPD), COVID-19, other infections, and other conditions (asthma exacerbation, haemoptysis, and bronchoaspirations). 30-day mortality, intensive-care unit admission, and invasive and non-invasive mechanical ventilation were secondary outcomes. Eight EWSs, namely, the National Early Warning Score 2, the Modified Rapid Emergency Medicine Score, the Rapid Acute Physiology Score, the Quick Sequential Organ Failure Assessment Score, the CURB-65 Severity Score for Community-Acquired Pneumonia, the BAP-65 Score for Acute Exacerbation of COPD, the Quick COVID-19 Severity Index, and the Modified Sequential Organ Failure Assessment (mSOFA), were explored to determine their predictive validity through calibration, clinical net benefit as determined through decision curve analysis, and discrimination analysis (area under the curve of the receiver operating characteristic [AUROC], compared with Delong's test). FINDINGS: Between Jan 1, 2020, and Nov 31, 2022, 902 patients were enrolled. The global 2-day mortality rate was 87 (10%); in proportion to various respiratory conditions, the rates were 35 (40%) for dyspnoea, nine (10%) for COPD, 13 (15%) for COVID-19, 28 (32%) for other infections, and two (2%) for others conditions. mSOFA showed the best calibration, a higher net benefit, and the best discrimination (AUROC 0·911, 95% CI 0·86-0·95) for predicting 2-day mortality, and its discrimination was statistically significantly more accurate (p<0·0001) compared with the other scores. The performance of mSOFA for predicting 2-day mortality was higher than the other scores when considering the prehospital respiratory conditions, and was also higher for the secondary outcomes, except for non-invasive mechanical ventilation. INTERPRETATION: Our results showed that mSOFA outperformed other EWSs. The inclusion of mSOFA in prehospital decision making will entail a quick identification of patients in acute respiratory distress at high risk of deterioration, allowing prioritisation of resources and patient care. FUNDING: Gerencia Regional de Salud, Public Health System of Castilla y León (GRS Spain). TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Distinct phenotype of SARS-CoV-2 Omicron BA.1 in human primary cells but no increased host range in cell lines of putative mammalian reservoir species.

SARS-CoV-2's genetic plasticity has led to several variants of concern (VOCs). Here we studied replicative capacity for seven SARS-CoV-2 isolates (B.1, Alpha, Beta, Gamma, Delta, Zeta, and Omicron BA.1) in primary reconstituted airway epithelia (HAE) and lung-derived cell lines. Furthermore, to investigate the host range of Delta and Omicron compared to ancestral SARS-CoV-2, we assessed replication in 17 cell lines from 11 non-primate mammalian species, including bats, rodents, insectivores and carnivores. Only Omicron's phenotype differed in vitro, with rapid but short replication and efficient production of infectious virus in nasal HAEs, in contrast to other VOCs, but not in lung cell lines. No increased infection efficiency for other species was observed, but Delta and Omicron infection efficiency was increased in A549 cells. Notably replication in A549 and Calu3 cells was lower than in nasal HAE. Our results suggest better adaptation of VOCs towards humans, without an extended host range, and may be relevant to the search for the putative intermediate host and reservoirs prior to the pandemic.

Is the Combination of Robot-Assisted Therapy and Transcranial Direct Current Stimulation Useful for Upper Limb Motor Recovery? A Systematic Review with Meta-Analysis.

Stroke is the third leading cause of disability in the world, and effective rehabilitation is needed to improve lost functionality post-stroke. In this regard, robot-assisted therapy (RAT) and transcranial direct current stimulation (tDCS) are promising rehabilitative approaches that have been shown to be effective in motor recovery. In the past decade, they have been combined to study whether their combination produces adjuvant and greater effects on stroke recovery. The aim of this study was to estimate the effectiveness of the combined use of RATs and tDCS in the motor recovery of the upper extremities after stroke. After reviewing 227 studies, we included nine randomised clinical trials (RCTs) in this study. We analysed the methodological quality of all nine RCTs in the meta-analysis. The analysed outcomes were deficit severity, hand dexterity, spasticity, and activity. The addition of tDCS to RAT produced a negligible additional benefit on the effects of upper limb function (SMD -0.09, 95% CI -0.31 to 0.12), hand dexterity (SMD 0.12, 95% CI -0.22 to 0.46), spasticity (SMD 0.04, 95% CI -0.24 to 0.32), and activity (SMD 0.66, 95% CI -1.82 to 3.14). There is no evidence of an additional effect when adding tDCS to RAT for upper limb recovery after stroke. Combining tDCS with RAT does not improve upper limb motor function, spasticity, and/or hand dexterity. Future research should focus on the use of RAT protocols in which the patient is given an active role, focusing on the intensity and dosage, and determining how certain variables influence the success of RAT.

Combining transcranial direct current stimulation with hand robotic rehabilitation in chronic stroke patients: a double blind randomized clinical trial.

OBJECTIVE: This study aimed to assess the impact of combining transcranial direct current stimulation (tDCS) with end-effector robot-assisted treatment (RAT) on upper limb function, spasticity, and hand dexterity in chronic stroke patients. DESIGN: This was a prospective, double-blind randomized trial with 20 equally allocated stroke patients. The experimental group received dual-tDCS (anode over affected M1, cathode over contralateral M1) alongside RAT, while the control group received sham tDCS with the same electrode placement + RAT. Each patient underwent 20 combined tDCS and RAT sessions. The primary outcome measure was the Fugl Meyer Upper Limb motor score (mFM-UL), with secondary outcomes including AMADEO® kinematic measures, Action Research Arm Test (ARAT), and Functional Independence Measure (FIM). Assessments were conducted at baseline, post-rehabilitation, and three months later. RESULTS: Combining bilateral tDCS with RAT did not yield additional improvements in mFM-UL, FIM, or ARAT scores among stroke patients. However, the real tDCS group showed enhanced finger flexion in the affected hand based on AMADEO® kinematic measures. CONCLUSION: The addition of tDCS to RAT did not result in significant overall functional improvements in chronic stroke patients. However, a benefit was observed in finger flexion of the affected hand.