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Impaired lipid metabolism is a pivotal driver of cardiovascular disease (CVD). In this regard, the accumulation of ceramides within the circulation as well as in metabolically active tissues and atherosclerotic plaques is a direct consequence of derailed lipid metabolism. Ceramides may be at the nexus between impaired lipid metabolism and CVD. Indeed, although on one hand ceramides have been implicated in the pathogenesis of CVD, on the other specific ceramide subspecies have also been proposed as predictors of major adverse cardiovascular events. This review will provide an updated overview of the role of ceramides in the pathogenesis of CVD, as well as their pathogenetic mechanisms of action. Furthermore, the manuscript will cover the importance of ceramides as biomarkers to predict cardiovascular events and the role of diet, both in terms of nutrients and dietary patterns, in modulating ceramide metabolism and homeostasis.
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Enfermedades Cardiovasculares , Ceramidas , Dieta , Metabolismo de los Lípidos , Ceramidas/metabolismo , Humanos , Enfermedades Cardiovasculares/etiología , Biomarcadores/sangre , Animales , HomeostasisRESUMEN
OBJECTIVE: To characterise sex and gender-based analysis (SGBA) and diversity metric reporting, representation of female/women participants in acute care trials and temporal changes in reporting before and after publication of the 2016 Sex and Gender Equity in Research guideline. DESIGN: Systematic review. DATA SOURCES: We searched MEDLINE for trials published in five leading medical journals in 2014, 2018 and 2020. STUDY SELECTION: Trials that enrolled acutely ill adults, compared two or more interventions and reported at least one clinical outcome. DATA ABSTRACTION AND SYNTHESIS: 4 reviewers screened citations and 22 reviewers abstracted data, in duplicate. We compared reporting differences between intensive care unit (ICU) and cardiology trials. RESULTS: We included 88 trials (75 (85.2%) ICU and 13 (14.8%) cardiology) (n=111 428; 38 140 (34.2%) females/women). Of 23 (26.1%) trials that reported an SGBA, most used a forest plot (22 (95.7%)), were prespecified (21 (91.3%)) and reported a sex-by-intervention interaction with a significance test (19 (82.6%)). Discordant sex and gender terminology were found between headings and subheadings within baseline characteristics tables (17/32 (53.1%)) and between baseline characteristics tables and SGBA (4/23 (17.4%)). Only 25 acute care trials (28.4%) reported race or ethnicity. Participants were predominantly white (78.8%) and male/men (65.8%). No trial reported gendered-social factors. SGBA reporting and female/women representation did not improve temporally. Compared with ICU trials, cardiology trials reported significantly more SGBA (15/75 (20%) vs 8/13 (61.5%) p=0.005). CONCLUSIONS: Acute care trials in leading medical journals infrequently included SGBA, female/women and non-white trial participants, reported race or ethnicity and never reported gender-related factors. Substantial opportunity exists to improve SGBA and diversity metric reporting and recruitment of female/women participants in acute care trials. PROSPERO REGISTRATION NUMBER: CRD42022282565.
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Cuidados Críticos , Humanos , Femenino , Masculino , Cuidados Críticos/estadística & datos numéricos , Publicaciones Periódicas como Asunto/estadística & datos numéricos , Factores Sexuales , Factor de Impacto de la Revista , Ensayos Clínicos como Asunto , Equidad de Género , CardiologíaRESUMEN
HDL-cholesterol quality, including cholesterol distribution in HDL subfractions, is emerging as a key discriminant in dictating the effects of these lipoproteins on cardiovascular health. This study aims at elucidating the relationship between cholesterol distribution in HDL subfractions and CVD risk factors as well as diet quality and energy density in a population of pre- and postmenopausal women. Seventy-two women aged 52 ± 6 years were characterized metabolically and anthropometrically. Serum HDL-C subfractions were quantified using the Lipoprint HDL System. Cholesterol distribution in large HDL subfractions was lower in overweight individuals and study participants with moderate to high estimated CVD risk, hypertension, or insulin resistance. Cholesterol distribution in large, as opposed to small, HDL subfractions correlated negatively with insulin resistance, circulating triglycerides, and visceral adipose tissue (VAT). VAT was an independent positive and negative predictor of cholesterol distribution in large and small HDL subfractions, respectively. Furthermore, an increase in energy intake could predict a decrease in cholesterol levels in large HDL subfractions while lipid intake positively predicted cholesterol levels in small HDL subfractions. Cholesterol distribution in HDL subfractions may represent an additional player in shaping CVD risk and a novel potential mediator of the effect of diet on cardiovascular health.
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Enfermedades Cardiovasculares , HDL-Colesterol , Grasas de la Dieta , Grasa Intraabdominal , Adulto , Femenino , Humanos , Persona de Mediana Edad , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , HDL-Colesterol/sangre , Dieta , Grasas de la Dieta/efectos adversos , Factores de Riesgo de Enfermedad Cardiaca , Resistencia a la Insulina , Grasa Intraabdominal/metabolismo , Obesidad Abdominal/sangre , Obesidad Abdominal/epidemiología , Factores de Riesgo , Triglicéridos/sangreRESUMEN
Introduction: Eggerthia catenaformis, a non-spore-forming anaerobic Gram-positive bacillus component of the human fecal microbiota has rarely been reported in human diseases. In almost every case described in current literature to date, dental diseases (abscesses, periodontitis, or caries), are the most common source of the infection which extends to the brain, cervical spaces, pulmonary parenchyma, the pleural cavity, the abdominal wall, and the abdominal cavity. Case report: An 82-year-old male Caucasian patient was admitted to our Emergency Department (ED) with a painless, right submandibular mass, dyspnea, and inspiratory stridor. A CT scan of the head, neck, and chest with intravenous contrast material revealed a retrotonsillar fluid collection. Air bubbles and minimal fluid were present from the right sub-mandibular area to the lower mediastinum between the spine, the descending thoracic aorta, and the trachea. The patient underwent surgical treatment and a broad-spectrum antibiotic. The retropharyngeal fluid collection culture showed the presence of Eggerthia catenaformis. After a first period in the Intensive Care Unit, he was admitted to a Step-Down Unit (SDU) where he underwent respiratory weaning, motor rehabilitation, and gradual oral feeding resumption. At discharge, the patient maintained the tracheal cannula as he still had impaired swallowing of solid foods. Conclusions: Here we report the first case of descending necrotizing mediastinitis in a patient with a retropharyngeal abscess, in the absence of dental diseases.
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Triple-negative breast cancer (TNBC) accounts for almost 15% of all diagnosed breast cancers and often presents high rates of relapses and metastases, with generally poor prognosis despite multiple lines of treatment. Immunotherapy has radically changed the approach of clinicians towards TNBC in the last two to three years, even if targeted and specific therapeutic options are still missing; this unmet need is further justified by the extreme molecular and clinical heterogeneity of this subtype of breast cancer and by the weak response to both single-agent and combined therapies. In March 2023, the National Comprehensive Cancer Network (NCCN), the main association of cancer centers in the United States, released the last clinical practice guidelines, with an update on classic and novel approaches in the field of breast cancer. The purpose of this comprehensive review is to summarize the latest findings in the setting of metastatic TNBC treatment, focusing on each category of drugs approved by the Food and Drug Administration (FDA) and included in the NCCN guidelines. We also introduce part of the latest published studies, which have reported new and promising molecules able to specifically target some of the biomarkers involved in TNBC pathogenesis. We searched the PubMed and Scopus databases for free full texts reported in the literature of the last 5 years, using the words "triple-negative breast cancer" or "TNBC" or "basal-like". The articles were analyzed by the authors independently and double-blindly, and a total of 114 articles were included in the review.
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Risk prediction models are fundamental to effectively triage incoming COVID-19 patients. However, current triaging methods often have poor predictive performance, are based on variables that are expensive to measure, and often lead to hard-to-interpret decisions. We introduce two new classification methods that can predict COVID-19 mortality risk from the automatic analysis of routine clinical variables with high accuracy and interpretability. SVM22-GASS and Clinical-GASS classifiers leverage machine learning methods and clinical expertise, respectively. Both were developed using a derivation cohort of 499 patients from the first wave of the pandemic and were validated with an independent validation cohort of 250 patients from the second pandemic phase. The Clinical-GASS classifier is a threshold-based classifier that leverages the General Assessment of SARS-CoV-2 Severity (GASS) score, a COVID-19-specific clinical score that recently showed its effectiveness in predicting the COVID-19 mortality risk. The SVM22-GASS model is a binary classifier that non-linearly processes clinical data using a Support Vector Machine (SVM). In this study, we show that SMV22-GASS was able to predict the mortality risk of the validation cohort with an AUC of 0.87 and an accuracy of 0.88, better than most scores previously developed. Similarly, the Clinical-GASS classifier predicted the mortality risk of the validation cohort with an AUC of 0.77 and an accuracy of 0.78, on par with other established and emerging machine-learning-based methods. Our results demonstrate the feasibility of accurate COVID-19 mortality risk prediction using only routine clinical variables, readily collected in the early stages of hospital admission.
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Biological sex and sociocultural gender are emerging as pivotal modifiers of health and diseases. Sex-based differences exist in the development, pathogenesis, and management of individuals with pulmonary arterial hypertension (PAH). The interplay between gender domains (ie, identity, roles, relations, and institutionalized gender) and PAH has been barely investigated. The aim of this narrative review is to describe up-to-date evidence on the integration of sex and gender in PAH research, highlighting areas for future investigation.
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Hipertensión Pulmonar , Masculino , Femenino , Humanos , Hipertensión Pulmonar/epidemiología , Hipertensión Pulmonar/terapia , Caracteres SexualesRESUMEN
Chordoma is a rare slow-growing neoplastic bone lesion. However, they show an invasive local growth and high recurrence rate, leading to an overall survival rate of 65% at 5 years and 35% at 10 years. We conducted a pooled and meta-analysis comparing recurrence rate, post-operative-complications, and survival in patients undergoing either microsurgical (MA) or endoscopic approaches (EA). Search of literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify surgical series of clivus chordomas published between January 1990 and March 2018 on Pubmed, Scopus, and Cochrane. Two different statistical analyses have been performed: a pooled analysis and a single-arm meta-analysis of overall recurrence rate and subgroup meta-analysis of complications in the subgroups open surgery and endoscopic surgery. After full-text screening, a total of 58 articles were included in the pooled analysis and 27 studies were included for the study-level meta-analysis. Pooled analysis-the extent of resection was the only association that remained significant (subtotal: HR = 2.18, p = 0.004; partial: HR = 4.40, p < 0.001). Recurrence was more prevalent among the surgical patients (45.5%) compared to endoscopic ones (23.7%). Meta-analysis-results of the cumulative meta-analysis showed an overall rate of recurrence of 25.6%. MA recurrence rate was 31.8% (99% CI 14-52.8), EA recurrence rate was 19.4% (5.4-39.2). CSF leak rate for the endoscopic group was 10.3% (99%CI 5-17.3) and 9.5% (99%CI 1.2-24.6) for the open surgery group. The partial removal versus total removal has an influence on recurrence rate (p < 0.001). MA recurrence rate was 31.8%; EA recurrence rate was 19.4%. The extent of resection is confirmed as a statistically significant factor affecting the risk for recurrence both with the pooled analysis and with the meta-analysis. Meta-analysis demonstrated that older patients tend to recur more than young patients, especially in surgical group.
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Cordoma/cirugía , Fosa Craneal Posterior/cirugía , Microcirugia/métodos , Neuroendoscopía/métodos , Neoplasias de la Base del Cráneo/cirugía , Cordoma/diagnóstico , Humanos , Microcirugia/efectos adversos , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/cirugía , Neuroendoscopía/efectos adversos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Neoplasias de la Base del Cráneo/diagnóstico , Resultado del TratamientoRESUMEN
OBJECTIVE: Traumatic spinal injury (TSI) is a global health issue contributing to morbidity and mortality, especially in low- and middle-income countries. The aim of this study is to compare the epidemiological estimates of TSI with the corresponding amount of published papers for different regions. METHODS: A bibliometric analysis was performed by collecting the number of publications concerning TSI from the PubMed database. Results were sorted according to the different geographical World Health Organization regions. A "publication-to-volume ratio" was obtained by comparing the average number of documents per year with the number of TSI cases across each region. RESULTS: A total of 2304 articles were detected from 2008 to 2018. The major publishing regions were North America (AMR-US/Can: 843 articles, 36.6%) and Europe (EUR: 833, 36.2%), then Western Pacific (WPR: 410, 17.8%), Eastern Mediterranean (EMR: 73, 3.2%), South-East Asia (SEAR: 71, 3.1%), Latin America (AMR-L: 55, 2.4%), Africa (AFR: 19, 0.8%). The United States is the most publishing country in AMR-US/Can (86.0%), and Germany in EUR (22.4%). In 2018, EUR published 36.6% of papers versus AMR-US/Can 26.5% and WPR 25.7%, thanks to an increase in Chinese publications. The highest publication ratios of 4.63 and 2.68 were found for AMR-US/Can and EUR, respectively. The other were EMR (0.22), WPR (0.18), AMR-L (0.07), SEAR (0.03), and AFR (0.01). CONCLUSIONS: A marked divide is currently found between countries with a high burden of TSI and those where there is most research interest, estimated as amount of publications. Data demonstrate the need for increased inclusiveness in guidelines generation from high-income countries including collection and analysis from low- and middle-income countries.
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Salud Global , Edición/estadística & datos numéricos , Traumatismos de la Médula Espinal/epidemiología , Traumatismos Vertebrales/epidemiología , África/epidemiología , Asia/epidemiología , Bibliometría , Países en Desarrollo , Europa (Continente)/epidemiología , Humanos , América Latina/epidemiología , América del Norte/epidemiología , Oceanía/epidemiología , Organización Mundial de la SaludRESUMEN
OBJECTIVE: Traumatic brain injury (TBI) is a global public health problem and more than 70% of trauma-related deaths are estimated to occur in low- and middle-income countries (LMICs). Nevertheless, there is a consistent lack of data from these countries. The aim of this work is to estimate the capacity of different and heterogeneous areas of the world to report and publish data on TBI. In addition, we wanted to estimate the countries with the highest and lowest number of publications when taking into account the relative TBI burden. METHODS: First, a bibliometric analysis of all the publications about TBI available in the PubMed database from January 1, 2008, to December 31, 2018, was performed. These data were tabulated by country and grouped according to each geographical region as indicated by the WHO: African Region (AFR), Region of the Americas (PAH), South-East Asia Region (SEAR), European Region (EUR), Eastern Mediterranean Region (EMR), and Western Pacific Region (WPR). In this analysis, PAH was further subdivided into Latin America (AMR-L) and North America (AMR-US/Can). Then a "publication to TBI volume ratio" was derived to estimate the research interest in TBI with respect to the frequency of this pathology. RESULTS: Between 2008 and 2018 a total of 8144 articles were published and indexed in the PubMed database about TBI. Leading WHO regions in terms of contributions were AMR-US/Can with 4183 articles (51.36%), followed by EUR with 2003 articles (24.60%), WPR with 1507 (18.50%), AMR-L with 141 articles (1.73%), EMR with 135 (1.66%), AFR with 91 articles (1.12%), and SEAR with 84 articles (1.03%). The highest publication to TBI volume ratios were found for AMR-US/Can (90.93) and EUR (21.54), followed by WPR (8.71) and AMR-L (2.43). Almost 90 times lower than the ratio of AMR-US/Can were the ratios for AFR (1.15) and SEAR (0.46). CONCLUSIONS: An important disparity currently exists between countries with a high burden of TBI and those in which most of the research is conducted. A call for improvement of data collection and research outputs along with an increase in international collaboration could quantitatively and qualitatively improve the ability of LMICs to ameliorate TBI care and develop clinical practice guidelines.
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Bibliometría , Investigación Biomédica , Lesiones Traumáticas del Encéfalo/epidemiología , Países Desarrollados , Países en Desarrollo , Lesiones Traumáticas del Encéfalo/diagnóstico , Lesiones Traumáticas del Encéfalo/terapia , Costo de Enfermedad , HumanosRESUMEN
OBJECTIVE: In 2015, the Lancet Commission on Global Surgery highlighted the disparities in surgical care worldwide. The aim of the present study was to investigate the research productivity of low-income countries (LICs) and low- to middle-income countries (LMICs) in selected journals representing the worldwide neurosurgical data and their ability to report and communicate globally the existing differences between high-income countries (HICs) and LMICs. METHODS: We performed a retrospective bibliometric analysis using PubMed and Scopus databases to record all the reports from 2015 to 2017 by investigators affiliated with neurosurgical departments in LICs and LMICs. RESULTS: A total of 8459 reports by investigators self-identified as members of neurosurgery departments worldwide were identified. Of these, 6708 reports were included in accordance with our method in the final analysis. The systematic search resulted in 459 studies reported by LICs and LMICs. Of these, 334 reports were included for the full text evaluation. Of the 6708 reports, 303 (4.52%) had been reported with an LMIC affiliation and only 31 (0.46%) with an LIC. The leading countries were India with 182 (54.5% among LMICs and LICs; 2.71% overall), followed by Egypt at 66 (19.76% among the LMICs and LICs; 0.98% overall), with a large difference compared with other countries such as Uganda at 9 (2.69% among the LMICs and LICs) and Tunisia and Pakistan at 8 each (2.4% among the LMICs and LICs). A few reports studies had been generated by collaboration with HIC neurosurgeons. CONCLUSIONS: Our results have shown that research studies from LMICs are underrepresented. Understanding and discussing the reasons for this underrepresentation are necessary to start addressing the disparities in neurosurgical research and care capacity. Future engagements from international journals, more partnership collaboration from HICs, and tailored funding to support investigators, collaborations, and networks could be of help.
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Bibliometría , Análisis de Datos , Países en Desarrollo/economía , Procedimientos Neuroquirúrgicos/economía , Pobreza/economía , Informe de Investigación , Humanos , Procedimientos Neuroquirúrgicos/tendencias , Pobreza/tendencias , Informe de Investigación/tendencias , Estudios RetrospectivosRESUMEN
BACKGROUND: In Cambodia, the most common victims of traumatic brain injury (TBI) are men 20-30 years of age involved in motor vehicle collision. Secondary injury sustained by these patients occurs during the time period between initial insult and hospital admission. Strengthening prehospital systems for TBI in low- and middle-income countries (LMICs) such as Cambodia is therefore a key element of the development agenda for universal health equity. We report a retrospective analysis of the relationship between prehospital delays and TBI outcomes among patients from a large government hospital in Cambodia. METHODS: Data were collected from 3476 patients with TBI admitted to a major government hospital in Phnom Penh, Cambodia, from June 2013 to June 2018. Patients with missing data or those admitted >8 hours postinjury were excluded. Statistical analyses examined associations between injury-to-admission delay (IAD) and outcomes such as Glasgow Outcome Scale (GOS) score and length of stay (LOS). RESULTS: A total of 2125 patients with TBI (76.85% men) were included. The median age was 27 years (interquartile range, 22-37 years). Injury severity at presentation included 1406 mild (66%), 464 moderate (22%), and 240 severe cases (11%). No Glasgow Coma Scale (GCS) data were available for 15 patients (1%). We found an inverse relationship between IAD and GOS score, most evidently for mild and moderate TBI (n = 1870; 88%). Regression analysis revealed a marked decrease in GOS score at the IAD >4-hour threshold. Each 30-minute delay in IAD was correlated with >2-hour increase in LOS for mild (P < 0.001) and moderate TBI (P < 0.001). CONCLUSIONS: In a retrospective cohort of >2000 patients with TBI from Cambodia, we found that increasing IAD was associated with worsening outcome, especially beyond the 4-hour threshold. These data should inform development of prehospital guidelines for TBI care in LMICs.