Effect of early vs. delayed extubation on functional outcome among patients with acute ischemic stroke treated with endovascular thrombectomy under general anesthesia: the prospective, randomized controlled EDESTROKE trial study protocol.

BACKGROUND: Recent meta-analyses and randomized studies have shown that among patients with acute ischemic stroke undergoing endovascular thrombectomy, general anesthesia with mechanical ventilation is associated with better functional status compared to local anesthesia and sedation, and they recommend its use. But once the procedure is completed, when is the optimal moment for extubation? Currently, there are no guidelines recommending the optimal moment for extubation. Prolonged mechanical ventilation time could potentially be linked to increased complications such as pneumonia or disturbances in cerebral blood flow due to the vasodilatation produced by most anesthetic drugs. However, premature extubation in a patient who has suffered a stroke could led to complications such as agitation, disorientation, abolished reflexes, sudden fluctuations in blood pressure, alterations in cerebral blood flow, respiratory distress, bronchial aspiration, and the need for reintubation. We therefore designed a randomized study hypothesizing that early compared with delayed extubation is associated with a better functional outcome 3 months after endovascular thrombectomy treatment under general anesthesia for acute ischemic stroke. METHODS: This investigator-initiated, single-center, prospective, parallel, evaluated blinded, superiority, randomized controlled trial will include 178 patients with a proximal occlusion of the anterior circulation treated with successful endovascular thrombectomy (TICI 2b-3) under general anesthesia. Patients will be randomly allocated to receive early (< 6 h) or delayed (6-12 h) extubation after the procedure. The primary outcome measure is functional independence (mRS of 0-2) at 90 days, measured with the modified Rankin Score (mRS), ranging from 0 (no symptoms) to 6 (death). DISCUSSION: This will be the first trial to compare the effect of mechanical ventilation duration (early vs delayed extubation) after satisfactory endovascular thrombectomy for acute ischemic stroke under general anesthesia. TRIAL REGISTRATION: The study protocol was approved April 11, 2023, by the by the Santiago-Lugo Research Ethics Committee (CEI-SL), number 2023/127, and was registered into the clinicaltrials.gov clinical trials registry with No. NCT05847309. Informed consent is required. Participant recruitment begins on April 18, 2023. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences.

Cytotoxicity and concentration of silver ions released from dressings in the treatment of infected wounds: a systematic review.

Introduction: Silver-releasing dressings are used in the treatment of infected wounds. Despite their widespread use, neither the amount of silver released nor the potential in vivo toxicity is known. The aim of this study was to evaluate the cytotoxic effects and the amount of silver released from commercially available dressings with infected wounds. Methods: The review was conducted according to the PRISMA statement. The Web of Science, PubMed, Embase, Scopus, and CINAHL databases were searched for studies from 2002 through December 2022. The criteria were as follows: population (human patients with infected wounds); intervention (commercial dressings with clinical silver authorized for use in humans); and outcomes (concentrations of silver ions released into tissues and plasma). Any study based on silver-free dressings, experimental dressings, or dressings not for clinical use in humans should be excluded. According to the type of study, systematic reviews, experimental, quasi-experimental, and observational studies in English, Spanish, or Portuguese were considered. The quality of the selected studies was assessed using the JBI critical appraisal tools. Studies that assessed at least 65% of the included items were included. Data were extracted independently by two reviewers. Results: 740 articles were found and five were finally selected (all of them quasi-experimental). Heterogeneity was found in terms of study design, application of silver dressings, and methods of assessment, which limited the comparability between studies. Conclusion: In vivo comparative studies of clinical dressings for control of infection lack a standardized methodology that allows observation of all the variables of silver performance at local and systemic levels, as well as evaluation of its cytotoxicity. It cannot be concluded whether the assessed concentrations of released silver in commercial dressings for the topical treatment of infected wounds are cytotoxic to skin cells. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022351041, PROSPERO [CRD42022351041].

Consensus document for lipid profile testing and reporting in Spanish clinical laboratories: what parameters should a basic lipid profile include?

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

Family Planning in Fertile-Age Patients With Multiple Sclerosis (MS) (ConPlanEM Study): Delphi Consensus Statements.

Family planning is essential for establishing Multiple Sclerosis (MS) prognosis, treatment decision, and disease monitoring. We aimed to generate an expert consensus addressing recommendations for family planning in MS patients of childbearing age. Initially, a committee comprising seven neurologists, experts in the MS field, identified the topics to be addressed. Then, the committee elaborated on different evidence-based preliminary statements. Next, using the Delphi methodology, a panel of neurologists manifested their level of agreement on the different statements using a Likert-type scale. Consensus was reached when ⩾70% of respondents expressed an agreement or disagreement using a five-point scale. Consensus was achieved on 47 out of 63 recommendations after three rounds of evaluations. The panel considered it essential to address family planning in all patients of childbearing age. There was also consensus that treatment should not be delayed due to the patient's desire for pregnancy. Additionally, in highly active patients, planning the pregnancy in the medium to long term using depletory drugs such as cladribine or alemtuzumab might represent a useful strategy. However, risks of adverse effects on the fetus due to drug-associated secondary autoimmunity should be addressed when alemtuzumab is considered. Moreover, the maintenance of natalizumab during pregnancy in very active patients reached expert consensus. Also, the panel supported the use of certain disease-modifying treatment (DMT) during lactation in selected cases. Our results identified specific areas of pregnancy planning in MS patients, where different treatment strategies might be considered to facilitate a safe and successful pregnancy while maintaining clinical and radiological stability.

Dietary Supplementation with Yerba Mate (Ilex paraguariensis) Infusion Increases IRS-1 and PI3K mRNA Levels and Enhances Insulin Sensitivity and Secretion in Rat Pancreatic Islets.

"Yerba mate" (YM), an aqueous extract of Ilex paraguariensis, has antioxidant, diuretic, cardio-protective and hypoglycaemic properties. Since its effect on the pancreatic islets remains unclear, we evaluated insulin sensitivity and glucose-stimulated insulin secretion (GSIS) in rats consuming YM or tap water (C) for 21 days. Glucose tolerance, glycemia, triglyceridemia, insulinemia, TBARS and FRAP serum levels were evaluated. GSIS and mRNA levels of insulin signaling pathway and inflammatory markers were measured in isolated pancreatic islets from both groups. In C rats, islets were incubated with YM extract or its phenolic components to measure GSIS. YM improved glucose tolerance, enhanced GSIS, increased FRAP plasma levels and islet mRNA levels of IRS-1 and PI3K (p110), and decreased TBARS plasma levels and islet gene expression of TNF-α and PAI-1. Islets from C rats incubated with 100 µg/mL dry YM extract, 1 µM chlorogenic acid, 0.1 and 1 µM rutin, 1 µM caffeic acid or 1 µM quercetin showed an increase in GSIS. Our results suggest that YM enhances glucose tolerance because of its positive effects on GSIS, oxidative stress rate and insulin sensitivity in rat islets, suggesting that long-term dietary supplementation with YM may improve glucose homeostasis in pre-diabetes or type 2 diabetes.

Consensus document for lipid profile testing and reporting in Spanish clinical laboratories: What parameters should a basic lipid profile include?

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

Consensus document for lipid profile testing and reporting in Spanish clinical laboratories.

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

Consensus document for lipid profile determination and reporting in Spanish clinical laboratories. What parameters should be included in a basic lipid profile? / Documento de consenso para la determinación e informe del perfil lipídico en laboratorios clínicos españoles: ¿Qué parámetros debe incluir un perfil lipídico básico?

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

In vitro effects of European and Latin-American medicinal plants in CYP3A4 gene expression, glutathione levels, and P-glycoprotein activity.

Many medicinal plants species from European -such as Artemisia absinthium, Equisetum arvense, Lamium album, Malva sylvestris, Morus nigra, Passiflora incarnata, Frangula purshiana, and Salix alba- as well as Latin American traditions -such as Libidibia ferrea, Bidens pilosa, Casearia sylvestris, Costus spicatus, Monteverdia ilicifolia, Persea americana, Schinus terebinthifolia, Solidago chilensis, Syzygium cumini, Handroanthus impetiginosus, and Vernonanthura phosphorica- are shortlisted by the Brazilian National Health System for future clinical use. However, they lack many data on their action upon some key ADME targets. In this study, we assess non-toxic concentrations (up to100 µg/ml) of their infusions for in vitro ability to modulate CYP3A4 mRNA gene expression and intracellular glutathione levels in HepG2 cells, as well as P-glycoprotein (P-gp) activity in vincristine-resistant Caco-2 cells (Caco-2 VCR). We further investigated the activation of human pregnane X receptor (hPXR) in transiently co-transfected HeLa cells and the inhibition of Gamma-glutamyl transferase (GGT) in HepG2 cells. Our results demonstrate L. ferrea, C. sylvestris , M. ilicifolia, P. americana, S. terebinthifolia, S. cumini, V. phosphorica, E. arvense, P. incarnata, F. purshiana, and S. alba can significantly increase CYP3A4 mRNA gene expression in HepG2 cells. Only F. purshiana shown to do so likely via hPXR activation. P-gp activity was affected by L. ferrea, F. purshiana, S. terebinthifolia, and S. cumini. Total intracellular glutathione levels were significantly depleted by exposure to all extracts except S. alba and S. cumini This was accompanied by a lower GGT activity in the case of C. spicatus, P. americana, S. alba, and S. terebinthifolia, whilst L. ferrea, P. incarnata and F. purshiana increased it. Surprisingly, S. cumini aqueous extract drastically decreased GGT activity (-48%, p < 0.01). In conclusion, this preclinical study shows that the administration of some of these herbal medicines causes in vitro disturbances to key drug metabolism mechanisms. We recommend active pharmacovigilance for Libidibia ferrea (Mart.) L. P. Queiroz, Frangula purshiana Cooper, Schinus terebinthifolia Raddi, and Salix alba L. which were able to alter all targets in our preclinical study.

[Design and validation of an instrument about quality of the advance care planning for professionals]. / Diseño y validación de un instrumento sobre calidad de la planificación anticipada de decisiones para profesionales.

OBJECTIVE: To develop a questionnaire aimed to measure the quality of the advance care planning process in healthcare professionals and to assess its psychometric quality. METHOD: Instrumental questionnaire validation study. SCOPE: primary care centers and outpatients clinics from general hospitals in Ferrol, Ourense, Monforte-Lugo and Health Area V of the Health Service of Asturias. PARTICIPANTS: physicians and nurses. Phases: (1) design of the first version of the questionnaire using the Delphi technique; (2) construction of the second version of 21 items, after judges' agreement and Kendall's W test; (3) pilot study: internal consistency using Cronbach's alpha and omega coefficient, retest-test by Pearson's correlation coefficient; (4) validation: Barlett's spherity test and Kaiser-Meyer-Olkin measurement, exploratory factor analysis with varimax rotation and study of the dimensions of the questionnaire (number, CCI and correlation), internal consistency using Cronbach's alpha. RESULTS: Pilot study with 28 professionals. Reliability É·=0.917, α=0.841, and test-retest correlation coefficient of 0.785 (95% confidence interval: 0.587-0.894; p<0.001). Validation of the questionnaire (21 items) in 204 professionals. Ítem analysis and exploratory factor analysis (Barlett's test [χ2=1298,789] and KMO=0.808; p<0.001) yielded a five-factor model explaining 64.377% of the total variance, with 18 items grouped into 5 dimensions (information, preferences, behavioral intention, training and communication). Cronbach's alpha of the global questionnaire was 0.841. CONCLUSIONS: The ProPAD-pro questionnaire has showed to be a valid and reliable instrument to assess the quality of the advance care planning process.

The Broad Concept of "Spasticity-Plus Syndrome" in Multiple Sclerosis: A Possible New Concept in the Management of Multiple Sclerosis Symptoms.

Multiple sclerosis (MS) pathology progressively affects multiple central nervous system (CNS) areas. Due to this fact, MS produces a wide array of symptoms. Symptomatic therapy of one MS symptom can cause or worsen other unwanted symptoms (anticholinergics used for bladder dysfunction produce impairment of cognition, many MS drugs produce erectile dysfunction, etc.). Appropriate symptomatic therapy is an unmet need. Several important functions/symptoms (muscle tone, sleep, bladder, pain) are mediated, in great part, in the brainstem. Cannabinoid receptors are distributed throughout the CNS irregularly: There is an accumulation of CB1 and CB2 receptors in the brainstem. Nabiximols (a combination of THC and CBD oromucosal spray) interact with both CB1 and CB2 receptors. In several clinical trials with Nabiximols for MS spasticity, the investigators report improvement not only in spasticity itself, but also in several functions/symptoms mentioned before (spasms, cramps, pain, gait, sleep, bladder function, fatigue, and possibly tremor). We can conceptualize and, therefore, hypothesize, through this indirect information, that it could be considered the existence of a broad "Spasticity-Plus Syndrome" that involves, a cluster of symptoms apart from spasticity itself, the rest of the mentioned functions/symptoms, probably because they are interlinked after the increase of muscle tone and mediated, at least in part, in the same or close areas of the brainstem. If this holds true, there exists the possibility to treat several spasticity-related symptoms induced by MS pathology with a single therapy, which would permit to avoid the unnecessary adverse effects produced by polytherapy. This would result in an important advance in the symptomatic management of MS.

The systematic review: Plurality of approaches and methodologies. / La revisión sistemática: pluralidad de enfoques y metodologías.

A systematic review is considered a "special" type of scientific article that, without being original, summarizes the current state of research on a particular topic, through a rigorous and reproducible systematic process. It emerged in order to offer a deeper insight and to understand a specific phenomenon of reality, based on the results of other research to consolidate existing knowledge and identify unresolved problems. This could facilitate decision-making according to the evidence. However, many synonyms are included under the generic term "review" that, through ignorance or misuse, can be disconcerting. This article explores the different types of published systematic reviews that we can find published, depending on the organization of their approach and the knowledge synthesis methodology used.

Quality of clinical practice guidelines of lower extremity venous ulcers. / Calidad de las guías de práctica clínica sobre úlceras venosas de la extremidad inferior.

The clinical variability and professional uncertainty in the prevention and treatment of lower extremity venous ulcers (VU) has as a main consequence, the fact that patients can be subjected to diagnostic and therapeutic tests, sometimes of dubious utility, these may even be harmful to the health of the patient and that, at other times, certain procedures or processes that may be appropriate to the patient's situation and needs may be omitted. It is for this reason that a series of specific documents called clinical practice guidelines for the approach of VU (CPG-VU) have been created, with the aim of improving the effectiveness and quality of care, reducing unjustified variability and establishing homogeneous criteria for its handling. Nevertheless, the literature shows that not all CPGs have the same methodological and evidence-drawing criteria. Many of them are of poor scientific quality and editorial rigor. This implies that CPGs should be periodically reviewed and updated based on the most current evidence and their quality contrasted with validated instruments such as AGREE-II. After an analysis of the quality of six CPG-VU available today, it has been possible to identify what guidelines are recommended for its implementation in the practice of care, which should be modified to improve their applicability and development of the evidence.

[Implementing evidence and implementation research: two different and prime realities]. / Implementar evidencias e investigar en implementación: dos realidades diferentes y prioritarias.

Scientific research can contribute to more efficient health care, enhance care quality and safety of persons. In order for this to happen, the knowledge gained must be put into practice. Implementation is known as the introduction of a change or innovation to daily practice, which requires effective communication and the elimination of barriers that hinder this process. Best practice implementation experiences are being used increasingly in the field of nursing. The difficulty in identifying the factors that indicate the success or failure of implementation has led to increased studies to build a body of differentiated knowledge, recognized as implementation science or implementation research. Implementation research is the scientific study whose objective is the adoption and systematic incorporation of research findings into clinical practice to improve the quality and efficiency of health services. The purpose of implementation research is to improve the health of the population through equitable and effective implementation of rigorously evaluated scientific knowledge, which involves gathering the evidence that has a positive impact on the health of the community. In this text, we set out the characteristics of nursing implementation research, providing a synthesis of different methods, theories, key frameworks and implementation strategies, along with the terminology proposed for greater conceptual clarity.

Effects of diazoxide in multiple sclerosis: A randomized, double-blind phase 2 clinical trial.

OBJECTIVE: The aim of this study was to test the safety of diazoxide and to search for signs of efficacy in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: In this multicenter, randomized, placebo-controlled, double-blind trial (treatment allocation was concealed), 102 patients with RRMS were randomized to receive a daily oral dose of diazoxide (0.3 and 4 mg/d) or placebo for 24 weeks (NCT01428726). The primary endpoint was the cumulative number of new T1 gadolinium-enhancing lesions per patient, recorded every 4 weeks from week 4 to week 24. Secondary endpoints included brain MRI variables such as the number of new/enlarging T2 lesions and the percentage brain volume change (PBVC); clinical variables such as the percentage of relapse-free patients, relapse rate, and change in the Expanded Disability Status Scale score; and safety and tolerability. RESULTS: Diazoxide was well-tolerated and it produced no serious adverse events other than 1 case of Hashimoto disease. At the 2 doses tested, diazoxide did not improve the primary endpoint or the MRI and clinical variables related to the presence of new lesions or relapses. Patients treated with diazoxide showed reduced PBVC compared with the placebo group, although such changes could be confounded by the higher disease activity of the treated group and the vascular effects of diazoxide. CONCLUSION: At the doses tested, oral diazoxide did not decrease the appearance of new lesions evident by MRI. The effects in slowing the progression of brain atrophy require further validation. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with RRMS, diazoxide (0.3 and 4 mg/d) does not significantly change the number of new MRI T1 gadolinium-enhancing lesions.

Effects of 20-hydroxyecdysone, Leuzea carthamoides extracts, dexamethasone and their combinations on the NF-κB activation in HeLa cells.

OBJECTIVES: The plant steroid 20-hydroxyecdysterone (20E) and 20E-containing extracts from Leuzea carthamoides (Willd.) DC are sold with claims of anabolic and immunomodulatory effects. Yet their effect on the activation of nuclear factor kappa B (NF-κB), a key player in immune response and cell fate, and their influence on the NF-κB-inhibiting activity of steroidal anti-inflammatory drugs is still unknown. METHODS: The ability of 20E, Leuzea extracts and selected steroidal/non-steroidal anti-inflammatory drugs to influence the activation of NF-κB was explored using, as the experimental model, human cervical cancer HeLa-IL-6 cells stably transfected with an IL-6-bound reporter gene. Effects on cell viability and proliferation were monitored (MTT assay). HPLC-DAD was used to establish links between chemical patterns of Leuzea extracts and their bioactivities. KEY FINDINGS: 20E inhibited NF-κB activation (IC50 31.8 µm) but was less active than other plant metabolites (xanthohumol 3.8 µm, withaferin A 1.4 µm). Leuzea extracts with high content in 20E had a fair activating effect, but in contrast, some extracts with low 20E content significantly inhibited NF-κB activation at IC50s ranging from 3.5 to 6.2 µg/ml. Combination tests confirmed that 20E does not explain the NF-κB modulation achieved by Leuzea extracts. The extracts but not 20E itself showed a significant modulation of the NF-κB inhibitory effect of dexamethasone. CONCLUSIONS: 20E is unlikely a major player in the NF-κB inhibitory effects displayed by some Leuzea extracts in vitro. If confirmed in vivo, caution should prevail towards marketed Leuzea extracts that are non-standardised or standardised on 20E only, since different starting materials and extracts may even cause opposite effects. More importantly, our results indicate the interaction potential of Leuzea with steroidal anti-inflammatory drugs.