Intracardiac vs Transesophageal Echocardiography for Left Atrial Appendage Occlusion: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: Multiple studies continue to evaluate the use of intracardiac echocardiography (ICE) and transesophageal echocardiography (TEE) for guiding left atrial appendage occlusion (LAAO). OBJECTIVE: To conduct an updated meta-analysis comparing the effectiveness and safety outcomes of both imaging modalities. METHODS: PubMed, Cochrane, and Embase were searched for studies comparing ICE vs TEE to guide LAAO. Odds ratios (OR) with 95% confidence intervals (CI) were pooled using a random-effects model. The primary effectiveness endpoint was procedural success. The primary safety endpoint included the overall complications rate. Additional safety outcomes were assessed as secondary endpoints. Subgroup analysis of primary endpoints was conducted according to device type (Amulet, LAmbre, Watchman, Watchman FLX) and study region (American, Asia, Europe). We used R version 4.3.1 for all statistical analyses. RESULTS: Our meta-analysis included 19 observational studies encompassing 42,474 patients, of whom 4,415 (10.4%) underwent ICE-guided LAAO. Compared with TEE, ICE was associated with a marginally higher procedural success (OR 1.33; 95% CI: 1.01-1.76; p=0.04; I2=0%). There was no significant difference in the overall complications rate (OR 1.02; 95% CI: 0.77-1.36; p=0.89; I2=5%). However, ICE showed higher rates of pericardial effusion (OR 2.11; 95% CI: 1.47-3.03; p<0.001; I2=0%) and residual iatrogenic atrial septal defect (iASD) (OR 1.52; 95% CI: 1.15-2.03; p<0.004; I2=0%). Subgroup analysis revealed variations in procedural success within the ICE group across study regions (p=0.02). CONCLUSION: In this updated meta-analysis, the increasing adoption of ICE-guided LAAO demonstrated higher procedural success rates compared to TEE, although with limited statistical significance. Overall complication rates were similar; however, ICE showed higher rates of pericardial effusion and residual iASD.

Mapping and Characterizing Instruments for Assessing Family Nurses' Workload: Scoping Review.

BACKGROUND: The importance of knowing the workload of family nurses lies essentially in the possibility of improving health outcomes, care processes and the nurse's professional life. There is a lack of studies that fully describe the nursing workload in primary care, particularly, in the context of family health nursing, and the ideal metrics to be used remain unknown, making it impossible to characterize and therefore provide the necessary insight to acknowledge the different contributions of several aspects that embody the global workload of family nurses. The objective of this scoping review was to map the known evidence and characterize the instruments used to assess the workload of family nurses. METHODS: Scoping review, according to the Joanna Briggs Institute, proposed a methodology for scoping reviews, consisting of three research stages: (1) an initial research in Medline and CINHAL; (2) an extended search, using keywords and search terms, in the following databases: JBI, CINAHL Complete, MEDLINE, Cochrane and Scopus; and (3) a search of the reference lists of the selected articles. No time limit was defined. RESULTS: Fourteen studies referring to ten assessment instruments were included. Nine of them analyze workload as a dimension of a broader instrument, and two studies refer to an instrument that focuses exclusively on workload. CONCLUSIONS: The diversity of professional competencies and contexts, the conceptual complexity of workload and the absence of a theoretical framework make it difficult to identify consensual instruments to assess the workload of family nurses. This study was prospectively registered with the Open Science Framework® on 6 September 2023, with the registration number: 3k6vr.

Direct oral anticoagulants in embolic stroke of undetermined source: an updated meta-analysis.

The efficacy and safety of direct oral anticoagulants (DOAC) in patients with embolic stroke of undetermined source (ESUS) remains unclear. We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCT) comparing DOACs versus aspirin in patients with ESUS. Risk ratios (RR) and 95% confidence intervals (CI) were computed for binary endpoints. Four RCTs comprising 13,970 patients were included. Compared with aspirin, DOACs showed no significant reduction of recurrent stroke (RR 0.95; 95% CI 0.84-1.09; p = 0.50; I2 = 0%), ischemic stroke or systemic embolism (RR 0.97; 95% CI 0.80-1.17; p = 0.72; I2 = 0%), ischemic stroke (RR 0.92; 95% CI 0.79-1.06; p = 0.23; I2 = 0%), and all-cause mortality (RR 1.11; 95% CI 0.87-1.42; p = 0.39; I2 = 0%). DOACs increased the risk of clinically relevant non-major bleeding (CRNB) (RR 1.52; 95% CI 1.20-1.93; p < 0.01; I2 = 7%) compared with aspirin, while no significant difference was observed in major bleeding between groups (RR 1.57; 95% CI 0.87-2.83; p = 0.14; I2 = 63%). In a subanalysis of patients with non-major risk factors for cardioembolism, there is no difference in recurrent stroke (RR 0.98; 95% CI 0.67-1.42; p = 0.90; I2 = 0%), all-cause mortality (RR 1.24; 95% CI 0.58-2.66; p = 0.57; I2 = 0%), and major bleeding (RR 1.00, 95% CI 0.32-3.08; p = 1.00; I2 = 0%) between groups. In patients with ESUS, DOACs did not reduce the risk of recurrent stroke, ischemic stroke or systemic embolism, or all-cause mortality. Although there was a significant increase in clinically relevant non-major bleeding, major bleeding was similar between DOACs and aspirin.

Critical thinking pedagogical practices in medical education: a systematic review.

Introduction: The development of critical thinking (CT) has been a universal goal in higher education. A systematic review of the literature was conducted to evaluate the effectiveness of currently used pedagogical practices to foster CT/ clinical reasoning (CR)/ clinical judgment (CJ) skills and/or dispositions in undergraduate medical students. Methods: PubMed, Web of Science and Scopus databases were searched from January 2010 to April 2021 with a predefined Boolean expression. Results: Of the 3221 articles originally identified, 33 articles were included by using PICOS methodology. From these, 21 (64%) reported CR pedagogical practices and 12 (36%) CT pedagogical practices. Discussion: Overall, pedagogical practices such as cognitive/visual representation, simulation, literature exposure, test-enhancing and team-based learning, clinical case discussion, error-based learning, game-based learning seem to enhance CT/CR skills and/or dispositions. Further research is required to identify the optimal timing, duration and modality of pedagogical interventions for effectively foster CT/CR in medical education.

Adjunctive Statin Therapy in Patients with Covid-19: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The efficacy and safety of adjunctive statin therapy in hospitalized patients with coronavirus disease 2019 (Covid-19) remains uncertain. METHODS: We systematically searched Medline, Embase, Cochrane, and ClinicalTrials.gov databases from inception to late April 2024 for randomized controlled trials (RCTs) comparing statin versus no statin use in patients hospitalized with Covid-19. We pooled risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) applying a random-effects model. R version 4.3.1 was used for statistical analyses. RESULTS: We included 7 RCTs comprising 4,262 patients, of whom 2,645 (62%) were randomized to receive statin therapy. Compared with no statin, statin use significantly reduced case-fatality rate (RR 0.88; 95% CI 0.80-0.98; I2 = 0%). In a time-to-event analysis, we found similar results (HR 0.86; 95% CI 0.75-0.99; I2 = 0%). Statin use also significantly reduced World Health Organization (WHO) scale at 14 days (mean difference -0.27; 95% CI -0.54 to -0.01; I2 = 0%). There was no statistically significant difference between the two groups in length of hospital stay, elevation of liver enzymes, and C-reactive protein levels. CONCLUSIONS: In patients hospitalized with Covid-19, statins significantly reduced case-fatality rate and WHO scale score. REGISTRATION: A prospective register was recorded in International Prospective Register of Systematic Reviews (PROSPERO) with the number CRD42023479007.

Efficacy and safety of neuroendoscopy surgery versus craniotomy for supratentorial intracerebral hemorrhage: an updated meta-analysis of randomized controlled trials.

Neuroendoscopy (NE) surgery emerged as a promising technique for the treatment of spontaneous intracerebral hemorrhage (ICH). A previous meta-analysis of randomized controlled trials (RCTs) analyzed the efficacy and safety of NE compared to craniotomy, but NE did not present a significant improvement in functional outcomes. However, a new study provided an opportunity to update the current knowledge. We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for RCTs reporting NE evacuation of spontaneous supratentorial ICH compared to craniotomy. The efficacy outcomes of interest were favorable functional outcome, functional disability, hematoma evacuation rate, and residual hematoma volume. The safety outcomes of interest were rebleeding, infection, and mortality. Seven RCTs were included containing 879 patients. The NE approach presented a significantly higher rate of favorable functional outcome compared with craniotomy (RR: 1.42; 95% CI 1.17, 1.73; p < 0.001). The evacuation rate was higher in patients who underwent the NE approach (MD: -8.36; 95% CI -12.66, -4.07; p < 0.001). NE did not show a benefit in improving the mortality rate (RR: 0.81, 95% CI 0.54, 1.22; p = 0.32). NE was associated with more favorable functional outcomes and lower rates of functional disabilities compared to craniotomy. Also, NE was superior regarding evacuation rate, while presenting a reduction in residual hematoma volume. NE might be associated with lower infection rates. Mortality was not improved by NE surgery. Larger, higher-quality randomized studies are needed to adequately evaluate the efficacy and safety of NE compared to craniotomy.

Venoarterial extracorporeal membrane oxygenation versus impella for cardiogenic shock in acute myocardial infarction: a systematic review and meta-analysis

BACKGROUND: Acute myocardial infarction (AMI) is an important cause of cardiogenic shock (CS). There is lack of evidence regarding the safety and efficacy of venoarterial extracorporeal membrane oxygenation (VA-ECMO) compared with Impella in this population. METHODS: We systematically searched PubMed, EMBASE, and Cochrane Library for studies comparing VA-ECMO with Impella in patients with CS related to AMI. The systematic review and meta-analysis followed Cochrane recommendations and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We used R version 4.3.1 for all statistical analyses. Odds ratios (OR) and 95% confidence intervals (CI) were pooled with a random-effects model. RESULTS: We included seven observational studies with 15.903 patients, of whom 12.943 (81.3%) were treated with Impella. There was no significant difference between groups regarding in-hospital mortality (OR 0.79; 95% CI 0.37-1.69; p=0.54; Figure 1A), ischemic stroke (OR 0.69; 95% CI 0.14-3.35; p=0.64; Figure 1B), acute kidney injury (OR 1.22; 95% CI 0.55-2.70; p=0.62), renal replacement therapy or dialysis (OR 1.02; 95% CI 0.33-3.19; p=0.97; Figure 1C), and blood transfusion (OR 0.52; 95% CI 0.16-1.72; p=0.28). CONCLUSION: In this meta-analysis, there was no significant difference between VA-ECMO and Impella among patients with CS and AMI for the outcomes of in-hospital mortality, ischemic stroke, acute kidney injury, renal replacement therapy, or blood transfusion.

Ticagrelor versus clopidogrel in dual antiplatelet therapy after minor stroke or transient ischemic attack: an updated network meta-analysis.

BACKGROUND: Dual antiplatelet therapy (DAPT) with clopidogrel plus aspirin is a well-established practice after a minor stroke or transient ischemic attack (TIA). However, ticagrelor plus aspirin may be an alternative. AIMS: We systematically searched PubMed, Embase, and Cochrane Central from inception to January 2024. We included randomized controlled trials (RCTs) enrolling adults with acute minor stroke or TIA within 72 hours of the onset of the symptoms. RESULTS: A total of 8 RCTs were included in our meta-analysis. Ticagrelor plus aspirin (RR, 0.70; 95% CrI 0.52, 0.91) and clopidogrel plus aspirin (RR, 0.79; 95% CrI 0.64, 0.98) were superior to aspirin in preventing stroke recurrence in overall analysis. Excluding studies with dual antiplatelet up to 90 days, ticagrelor plus aspirin was the only strategy that maintained superiority compared with aspirin regarding stroke recurrence (RR, 0.70; 95% CrI 0.51, 0.95) and ischemic stroke (RR, 0.68; 95% CrI 0.47, 0.94). There was no significant difference between treatment groups regarding hemorrhagic stroke, functional disability, and mortality. CONCLUSIONS: DAPTs were superior to aspirin in preventing recurrence or ischemic stroke. Although no significant difference was observed between DAPTs, ticagrelor plus aspirin may be related to worse major bleeding results, including intracranial bleeding. Ticagrelor plus aspirin is a considerable option for patients after a minor stroke or TIA.

Hair cortisol levels are associated with overweight and obesity in the ELSA-Brasil cohort.

Introduction: Hair cortisol level has recently been identified as a promising marker for detecting long-term cortisol levels and a marker of hypothalamic-pituitary-adrenal cortex (HPA) axis activity. However, research on the association between obesity and an altered cortisol metabolism remains controversial. Objective: This study aimed to investigate the relationship between hair cortisol levels and overweight and obesity in participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Methods: This was a cross-sectional study involving 2,499 participants from the second follow-up (visit 3, 2017-2019) attending research centers in Rio de Janeiro and Rio Grande do Sul states. Hair samples were collected, and cortisol levels were analyzed using enzyme-linked immunosorbent assay (ELISA) kits. Cortisol levels were classified as low (< 40 pg/mg), medium (40-128 pg/mg), or high (> 128 pg/mg). The participants were classified as eutrophic, overweight, or obese according to their weight (kg) and height (m2). Odds ratios (ORs) with 95% confidence intervals (95%CI) were estimated. Results: Of the 2499 individuals, 30% had eutrophic weight, 40% were overweight, and 30% were obese. Notably, cortisol levels gradually increased with increasing body weight. Among participants with high hair cortisol levels, 41.2% were classified as overweight and 34.2% as obese. Multinomial logistic regression analysis indicated that participants with high cortisol levels were 43% (OR =1.43; 95%CI: 1.02-2.03) more likely to be overweight and 72% (OR =1.72; 95%CI:1.20-2.47) more likely to be obese than participants with low hair cortisol levels. After adjustment for all covariates, high cortisol levels remained associated with obesity (OR = 1.54; 95%CI:1.02-2.31) and overweight (OR =1.33; 95%CI:0.91-1.94). Conclusion: In the ELSA-Brazil cohort, hair stress were positively associated with overweight and obesity. These results underscore the importance of considering stress and cortisol as potential factors in obesity prevention and intervention efforts, and highlight a novel aspect of the complex relationship between stress and obesity in the Brazilian population.

Brazil nut (Bertholletia excelsa H.B.K.) and Brazil nut oil: effects on oxidative stress and potential therapeutic health benefits from human, animal, and cell culture models.

Brazil nut (Bertholletia excelsa H.B.K.) is characterized by its high nutritional and energetic value. It contains high levels of l-arginine, antioxidant vitamins, phenolic compounds, and phytosterols. In addition to their biological functions, bioactive compounds and essential fatty acids present therapeutic effects on chronic disease prevention through their antioxidant effects. Thus, this review aims to present the most recent scientific evidence on the effect of Brazil nut on human health. A search for scientific articles was carried out through the MEDLINE/PubMed, Science Direct, and LILACS databases, considering articles published between the years 2010 and 2023. The results showed that Brazil nuts and Brazil nut oil, when consumed regularly and associated with a balanced diet, can improve lipid profile, attenuate inflammatory response, and improve oxidative stress through increased activity and gene expression of antioxidant enzymes. However, further studies are recommended to better understand the mechanisms of action.

The Association between Dietary Pattern, Obesity, and Glycemic Control of Children and Adolescents with Type 1 Diabetes Mellitus.

AIMS: To evaluate the association between dietary patterns, obesity, and glycemic control in children and adolescents with type 1 diabetes mellitus (T1DM). METHODS: A cross-sectional study was carried out in 2015 at a diabetes reference center in Rio de Janeiro. Sociodemographic data and those related to outpatient follow-ups were obtained from the medical records. The assessment of food consumption was performed using a 24 h food recall. Obesity was defined as body mass index-for-age (BMI-for-age) ≥ +1 z-score. Glycemic control was assessed using glycated hemoglobin (HbA1c). Dietary patterns were generated by factorial analysis, and each individual's adherence to these dietary patterns was determined by the factor loadings and then classified into terciles. RESULTS: The study population included 120 children and adolescents, among whom 5 dietary patterns were identified. The prevalence of obesity was 31.7% (n = 38), and 64.2% (n = 77) of the participants had inadequate glycemic control. We observed that individuals with higher adherence to dietary pattern five, characterized by a greater consumption of ultra-processed foods, had higher odds of having higher HbA1c levels (OR = 3.49; 95% CI = 1.18-11.16). CONCLUSIONS: Higher consumption of ultra-processed foods can be detrimental to glycemic control in children and adolescents. Thus, food intake monitoring is of paramount importance as part of the multidisciplinary care of patients with T1DM.

Exploring Professional Practice Environments and Organisational Context Factors Affecting Nurses' Adoption of Evidence-Based Practice: A Scoping Review.

This scoping review, conducted within the Joanna Briggs Institute (JBI) framework, analysed the recent literature (January 2018 to March 2023) addressing factors inherent to professional practice environments and organisational contexts influencing nurses' adoption of evidence-based practice (EBP). This review included studies involving nurses regardless of sector, practice setting, and scope of practice. A systematic search was undertaken across the PubMed, Web of Science, CINAHL, and MEDLINE databases, as well as the EThOS, OATD, and RCAAP platforms. The extracted textual elements underwent a content analysis, resulting in a coding structure established through an inductive approach that categorised information into main categories and subcategories linked by similarity and thematic affinity. Forty-one studies were included, revealing four main categories of factors impacting EBP adoption by nurses: (1) organisational dynamics, (2) management and leadership, (3) teamwork and communication, and (4) resources and infrastructure. The study's limitations acknowledge the subjective nature of categorisation, recognising potential variations based on individual perspectives despite adopting procedures to minimise the risk of bias. The results provide a substantial foundation for developing interventions to cultivate environments conducive to EBP adoption by nurses, thereby enhancing the integration of evidence into nurses' professional practice contexts. This review was prospectively registered on the Open Science Framework (registration no. osf.io/e86qz).

Video versus direct laryngoscopy in critically ill patients: an updated systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The utilization of video laryngoscopy (VL) has demonstrated superiority over direct laryngoscopy (DL) for intubation in surgical settings. However, its effectiveness in the intensive care unit and emergency department settings remains uncertain. METHODS: We systematically searched PubMed, Embase, Cochrane, and ClinicalTrials.gov databases for randomized controlled trials (RCTs) comparing VL versus DL in critically ill patients. Critical setting was defined as emergency department and intensive care unit. This systematic review and meta-analysis followed Cochrane and PRISMA recommendations. R version 4.3.1 was used for statistical analysis and heterogeneity was examined with I2 statistics. All outcomes were submitted to random-effect models. RESULTS: Our meta-analysis of 14 RCTs, compromising 3981 patients assigned to VL (n = 2002) or DL (n = 1979). Compared with DL, VL significantly increased successful intubations on the first attempt (RR 1.12; 95% CI 1.04-1.20; p < 0.01; I2 = 82%). Regarding adverse events, VL reduced the number of esophageal intubations (RR 0.44; 95% CI 0.24-0.80; p < 0.01; I2 = 0%) and incidence of aspiration episodes (RR 0.63; 95% CI 0.41-0.96; p = 0.03; I2 = 0%) compared to DL. CONCLUSION: VL is a more effective and safer strategy compared with DL for increasing successful intubations on the first attempt and reducing esophageal intubations in critically ill patients. Our findings support the routine use of VL in critically ill patients. Registration CRD42023439685 https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023439685 . Registered 6 July 2023.

Measles seroprevalence in adolescents and young adults living with HIV and response to MMR booster in seronegative ones.

OBJECTIVE: The study analyzed people with HIV (PWH) measles seroprevalence and response to MMR booster given to seronegative individuals. DESIGN: A prospective cohort study with four groups: vertically (v-HIV), horizontally infected (h-HIV) individuals, and two control groups. An MMR booster was offered to seronegative individuals. RESULTS: Measles seropositivity and IgG antibodies were significantly lower in v-HIV than in the other groups. All measles seronegative patients responded to booster. CONCLUSION: An MMR booster must be sought during adolescence in vertically PWH.

Cholesterol Exacerbates the Pathophysiology of Non-Alcoholic Steatohepatitis by Upregulating Hypoxia-Inducible Factor 1 and Modulating Microcirculatory Dysfunction.

Cholesterol is a pivotal lipotoxic molecule that contributes to the progression of Non-Alcoholic Steatohepatitis NASH). Additionally, microcirculatory changes are critical components of Non-Alcoholic Fatty Liver Disease (NAFLD) pathogenesis. This study aimed to investigate the role of cholesterol as an insult that modulates microcirculatory damage in NAFLD and the underlying mechanisms. The experimental model was established in male C57BL/6 mice fed a high-fat high-carbohydrate (HFHC) diet for 39 weeks. Between weeks 31-39, 2% cholesterol was added to the HFHC diet in a subgroup of mice. Leukocyte recruitment and hepatic stellate cells (HSC) activation in microcirculation were assessed using intravital microscopy. The hepatic microvascular blood flow (HMBF) was measured using laser speckle flowmetry. High cholesterol levels exacerbated hepatomegaly, hepatic steatosis, inflammation, fibrosis, and leukocyte recruitment compared to the HFHC group. In addition, cholesterol decreased the HMBF-cholesterol-induced activation of HSC and increased HIF1A expression in the liver. Furthermore, cholesterol promoted a pro-inflammatory cytokine profile with a Th1-type immune response (IFN-γ/IL-4). These findings suggest cholesterol exacerbates NAFLD progression through microcirculatory dysfunction and HIF1A upregulation through hypoxia and inflammation. This study highlights the importance of cholesterol-induced lipotoxicity, which causes microcirculatory dysfunction associated with NAFLD pathology, thus reinforcing the potential of lipotoxicity and microcirculation as therapeutic targets for NAFLD.

Relationship of the nursing practice environment with the quality of care and patients' safety in primary health care.

BACKGROUND: Nursing practice environment has impact on the quality of nursing care and on patients' and nurses' outcomes, namely better performances of these healthcare workers. Improving the nursing practice environment is a low-cost organizational strategy to achieve better patients' outcomes and retain qualified nurses, thus improving nursing care of units, healthcare organizations and healthcare system. This study aims to analyse the relationship between nursing practice environment and the nurses` perception of quality of care, patient safety, and safety culture in Primary Health Care in Portugal. METHODS: We conducted a descriptive, analytical, and cross-sectional study using data from RN4CAST Portugal. The sample was composed of 1059 nurses from 55 Health Center Groups of the mainland Portugal, 15 Health Centers of the Autonomous Region of Madeira and 6 Health Centers of the Autonomous Region of the Azores. Multivariate analysis and correlation analysis methods were used for data processing. RESULTS: Nurses consider that, in the Portuguese Primary Health Care, there is a mixed and unfavourable nursing practice environment, with a perception of a good quality of care, and both acceptable patients' safety and safety culture. The Collegial Nurse-Physician Relations and Nursing Foundations for Quality of Care dimensions to have the best ratings. The perception of Primary Health Care nurses on the dimension Nurse Participation in Organization Affairs was the one that showed the lowest score, followed by Staffing and Resource Adequacy and Nurse Manager Ability, Leadership, and Support of Nurses. Based on perception of nurses, the relationship between the nursing practice environment and the safety culture is higher, followed by the quality of care and patients' safety. CONCLUSIONS: The perception of Primary Health Care nurses is that there is an unfavourable and mixed nursing practice environment, with good quality of care, and acceptable patient safety and safety culture. The quality of the nursing practice environments is associated to better quality and safety of care. Thus, improving the nursing practice environments in healthcare organizations is a low-cost organizational strategy to achieve greater patients and nurses' outcomes, improving the quality of nursing care to patients in the Primary Health Care units.

A hitchhikers' guide to the terminology of accreditation processes for health professionals and institutions.

Accreditation processes for health care professions are designed to ensure that individuals and programs in these fields meet established standards of quality and effectiveness. The accelerating pace of globalization in the health care professions has increased the need for a shared understanding of the vocabulary of evaluation, assessment, and accreditation. The psychometric principles of valid and reliable assessment are commonly accepted, but the terminology is confusing. We believe that all stakeholders - evaluators, faculty, students but also the community - will benefit from a shared language and common set of definitions. We recognize that not all readers will agree with the definitions we propose, but we hope that this guide will help to ensure clarity, consistency, transparency, and fairness, and that it will promote through the stimulation of a debate greater collaboration across national and international boundaries.

Secretome as a Tool to Treat Neurological Conditions: Are We Ready?

Due to their characteristics, mesenchymal stem cells (MSCs) are considered a potential therapy for brain tissue injury or degeneration. Nevertheless, despite the promising results observed, there has been a growing interest in the use of cell-free therapies in regenerative medicine, such as the use of stem cell secretome. This review provides an in-depth compilation of data regarding the secretome composition, protocols used for its preparation, as well as existing information on the impact of secretome administration on various brain conditions, pointing out gaps and highlighting relevant findings. Moreover, due to the ability of MSCs to respond differently depending on their microenvironment, preconditioning of MSCs has been used to modulate their composition and, consequently, their therapeutic potential. The different strategies used to modulate the MSC secretome were also reviewed. Although secretome administration was effective in improving functional impairments, regeneration, neuroprotection, and reducing inflammation in brain tissue, a high variability in secretome preparation and administration was identified, compromising the transposition of preclinical data to clinical studies. Indeed, there are no reports of the use of secretome in clinical trials. Despite the existing limitations and lack of clinical data, secretome administration is a potential tool for the treatment of various diseases that impact the CNS.