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BACKGROUND: Elexacaftor-tezacaftor-ivacaftor has been approved in Europe for people with cystic fibrosis with at least one F508del CFTR variant. Additionally, it is approved by the US Food and Drug Administration (FDA) for people with cystic fibrosis with at least one of 177 rare variants. The aims of this study were to describe the clinical response to elexacaftor-tezacaftor-ivacaftor for people with cystic fibrosis without a F508del CFTR variant in France and to determine CFTR variant responsiveness to elexacaftor-tezacaftor-ivacaftor based on the observed clinical response. METHODS: The French compassionate programme expanded access to elexacaftor-tezacaftor-ivacaftor to people with cystic fibrosis, aged 6 years and older, without a F508del variant, excluding those with two variants previously characterised as non-responsive. Participants at France's 47 cystic fibrosis centres were given a 4-6 week trial of elexacaftor-tezacaftor-ivacaftor and response was determined by a centralised committee based on evolution of clinical data, lung function, and sweat chloride concentration. Responsiveness of individual CFTR variants was derived from observed clinical responses. FINDINGS: The first compassionnate programme was launched on May 19, 2022; by March 8, 2024, 516 people with cystic fibrosis had been identified for inclusion in this real-word study: 37 were not included due to the presence of two variants previously characterised as non-responsive to elexacaftor-tezacaftor-ivacaftor, and 479 (229 females [48%] and 250 males [52%]) received elexacaftor-tezacaftor-ivacaftor for 4-6 weeks. Among 443 participants who received no CFTR modulator before elexacaftor-tezacaftor-ivacaftor, 83 had at least one FDA-approved variant, of whom 81 (98%) were responders and continued elexacaftor-tezacaftor-ivacaftor; in responders, mean absolute change in sweat chloride was -44·5 mmol/L (95% CI -39·1 to -49·8) and percentage of predicted FEV1 (ppFEV1) was 11·1 percentage points (95% CI 8·4 to 13·7; both comparisons p<0·0001). Among 360 participants with no FDA-approved variant and no previous CFTR modulator, 177 (49%) were responders; in responders, mean absolute change in sweat chloride was -20·5 mmol/L (-17·2 to -23·8) and ppFEV1 was 13·2 percentage points (11·4 to 15·0; both comparisons p<0·0001). Among 36 participants who were receiving ivacaftor before elexacaftor-tezacaftor-ivacaftor, 32 (89%) continued elexacaftor-tezacaftor-ivacaftor. Of 251 individual CFTR variants, 64 (28 FDA-approved) were classified as responsive or possibly responsive to elexacaftor-tezacaftor-ivacaftor, and 123 (two FDA-approved) as non-responsive or possibly non-responsive to elexacaftor-tezacaftor-ivacaftor. INTERPRETATION: In France, over half of the population with cystic fibrosis without a F508del variant responded to elexacaftor-tezacaftor-ivacaftor, with most responders having no FDA-approved variant. The treatment period was relatively short and further research is warranted to describe the long-term safety and effectiveness of elexacaftor-tezacaftor-ivacaftor in this population. FUNDING: Association Vaincre la Mucoviscidose, Société Française de la Mucoviscidose, and Filière Maladies Rares MUCO-CFTR.
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OBJECTIVES: (1) To estimate the association of social risk factors with unplanned readmission and emergency care after a hospital stay. (2) To create a social risk scoring index. DATA SOURCES AND SETTING: We analyzed administrative data from the Department of Veterans Affairs (VA) Corporate Data Warehouse. Settings were VA medical centers that participated in a national social work staffing program. STUDY DESIGN: We grouped socially relevant diagnoses, screenings, assessments, and procedure codes into nine social risk domains. We used logistic regression to examine the extent to which domains predicted unplanned hospital readmission and emergency department (ED) use in 30 days after hospital discharge. Covariates were age, sex, and medical readmission risk score. We used model estimates to create a percentile score signaling Veterans' health-related social risk. DATA EXTRACTION: We included 156,690 Veterans' admissions to a VA hospital with discharged to home from 1 October, 2016 to 30 September, 2022. PRINCIPAL FINDINGS: The 30-day rate of unplanned readmission was 0.074 and of ED use was 0.240. After adjustment, the social risks with greatest probability of readmission were food insecurity (adjusted probability = 0.091 [95% confidence interval: 0.082, 0.101]), legal need (0.090 [0.079, 0.102]), and neighborhood deprivation (0.081 [0.081, 0.108]); versus no social risk (0.052). The greatest adjusted probabilities of ED use were among those who had experienced food insecurity (adjusted probability 0.28 [0.26, 0.30]), legal problems (0.28 [0.26, 0.30]), and violence (0.27 [0.25, 0.29]), versus no social risk (0.21). Veterans with social risk scores in the 95th percentile had greater rates of unplanned care than those with 95th percentile Care Assessment Needs score, a clinical prediction tool used in the VA. CONCLUSIONS: Veterans with social risks may need specialized interventions and targeted resources after a hospital stay. We propose a scoring method to rate social risk for use in clinical practice and future research.
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Background: Health care organizations, including the Veterans Health Administration (VHA), are increasingly adopting programs to address social determinants of health. As part of a comprehensive social risk screening and referral model, tailored resource guides can support efforts to address unmet social needs. However, limited guidance is available on best practices for the development of resource guides in health care settings. Observations: This article describes the development of geographically tailored resource guides for a national VHA quality improvement initiative, Assessing Circumstances and Offering Resources for Needs (ACORN), which aims to systematically screen for and address social needs among veterans. We outline the rationale for using resource guides as a social needs intervention and provide a pragmatic framework for resource guide development and maintenance. We offer guidance based on lessons learned from the development of ACORN resource guides, emphasizing a collaborative approach with VHA social workers and other frontline clinical staff, as well as with community-based organizations. Our how-to guide provides steps for identifying high-yield resources along with formatting considerations to maximize accessibility and usability among patients. Conclusions: Resource guides can serve as a valuable cross-cutting component of health care organizations' efforts to address social needs. We provide a practical approach to resource guide development that may support successful implementation within the VHA and other clinical settings.
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The field of electrophysiology (EP) has benefited from numerous seminal innovations and discoveries that have enabled clinicians to deliver therapies and interventions that save lives and promote quality of life. The rapid pace of innovation in EP may be hindered by several challenges including the aging population with increasing morbidity, the availability of multiple costly therapies that, in many instances, confer minor incremental benefit, the limitations of healthcare reimbursement, the lack of response to therapies by some patients, and the complications of the invasive procedures performed. To overcome these challenges and continue on a steadfast path of transformative innovation, the EP community must comprehensively explore how artificial intelligence (AI) can be applied to healthcare delivery, research, and education and consider all opportunities in which AI can catalyze innovation; create workflow, research, and education efficiencies; and improve patient outcomes at a lower cost. In this white paper, we define AI and discuss the potential of AI to revolutionize the EP field. We also address the requirements for implementing, maintaining, and enhancing quality when using AI and consider ethical, operational, and regulatory aspects of AI implementation. This manuscript will be followed by several perspective papers that will expand on some of these topics.
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Inteligencia Artificial , Electrofisiología Cardíaca , Atención a la Salud , Humanos , Investigación Biomédica , Técnicas Electrofisiológicas Cardíacas/métodosRESUMEN
Recent artificial intelligence (AI) advancements in cardiovascular care offer potential enhancements in effective diagnosis, treatment, and outcomes. More than 600 U.S. Food and Drug Administration-approved clinical AI algorithms now exist, with 10% focusing on cardiovascular applications, highlighting the growing opportunities for AI to augment care. This review discusses the latest advancements in the field of AI, with a particular focus on the utilization of multimodal inputs and the field of generative AI. Further discussions in this review involve an approach to understanding the larger context in which AI-augmented care may exist, and include a discussion of the need for rigorous evaluation, appropriate infrastructure for deployment, ethics and equity assessments, regulatory oversight, and viable business cases for deployment. Embracing this rapidly evolving technology while setting an appropriately high evaluation benchmark with careful and patient-centered implementation will be crucial for cardiology to leverage AI to enhance patient care and the provider experience.
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Inteligencia Artificial , Enfermedades Cardiovasculares , Humanos , Enfermedades Cardiovasculares/terapia , Enfermedades Cardiovasculares/diagnóstico , CardiologíaRESUMEN
Recent artificial intelligence (AI) advancements in cardiovascular care offer potential enhancements in diagnosis, treatment, and outcomes. Innovations to date focus on automating measurements, enhancing image quality, and detecting diseases using novel methods. Applications span wearables, electrocardiograms, echocardiography, angiography, genetics, and more. AI models detect diseases from electrocardiograms at accuracy not previously achieved by technology or human experts, including reduced ejection fraction, valvular heart disease, and other cardiomyopathies. However, AI's unique characteristics necessitate rigorous validation by addressing training methods, real-world efficacy, equity concerns, and long-term reliability. Despite an exponentially growing number of studies in cardiovascular AI, trials showing improvement in outcomes remain lacking. A number are currently underway. Embracing this rapidly evolving technology while setting a high evaluation benchmark will be crucial for cardiology to leverage AI to enhance patient care and the provider experience.
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Inteligencia Artificial , Enfermedades Cardiovasculares , Humanos , Enfermedades Cardiovasculares/terapia , Enfermedades Cardiovasculares/diagnóstico , Cardiología/métodosRESUMEN
Rationale: Limited data exist on the safety and effectiveness of elexacaftor-tezacaftor-ivacaftor (ETI) in people with cystic fibrosis (pwCF) and advanced lung disease. Objectives: To evaluate the effects of ETI in an unselected population of pwCF and advanced lung disease. Methods: A prospective observational study, including all adults aged 18 years and older with percentage predicted forced expiratory volume in 1 second (ppFEV1) ⩽ 40 who initiated ETI from December 2019 to June 2021 in France, was conducted. PwCF were followed until August 8, 2022. Results: ETI was initiated in 434 pwCF with a median ppFEV1 of 30 (interquartile range, 25-35), including 27 with severe cystic fibrosis liver disease and 183 with diabetes. PwCF were followed for a median of 587 (interquartile range, 396-728) days after ETI initiation. Discontinuation of ETI occurred in 12 (2.8%) pwCF and was due mostly to lung transplantation (n = 5) or death (n = 4). Absolute increase in ppFEV1 by a mean of +14.2% (95% confidence interval, 13.1-15.4%) occurred at 1 month and persisted throughout the study. Increase in ppFEV1 in the youngest age quartile was almost twice that of the oldest quartile (P < 0.001); body mass index < 18.5 kg/m2 was found in 38.6% at initiation versus 11.3% at 12 months (P = 0.0001). Increases in serum concentrations of vitamins A and E, but not 25-hydroxy vitamin D3, were observed. Significant reductions in the percentages of pwCF using oxygen therapy, noninvasive ventilation, nutritional support, and inhaled and systemic therapies (including antibiotics) were observed; insulin was discontinued in 12% of patients with diabetes. Conclusions: ETI is safe in pwCF and advanced lung disease, with multisystem pulmonary and extrapulmonary benefits.
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Aminofenoles , Benzodioxoles , Fibrosis Quística , Combinación de Medicamentos , Indoles , Quinolonas , Humanos , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/complicaciones , Masculino , Femenino , Adulto , Estudios Prospectivos , Indoles/uso terapéutico , Volumen Espiratorio Forzado , Aminofenoles/uso terapéutico , Quinolonas/uso terapéutico , Benzodioxoles/uso terapéutico , Persona de Mediana Edad , Pirazoles/uso terapéutico , Piridinas/uso terapéutico , Francia , Pirrolidinas/uso terapéutico , Adulto Joven , Agonistas de los Canales de Cloruro/uso terapéutico , QuinolinasRESUMEN
Mechanisms underlying the disruption of self-tolerance in acquired autoimmunity remain unclear. Immunoglobulin A (IgA) nephropathy is an acquired autoimmune disease where deglycosylated IgA1 (IgA subclass 1) auto-antigens are recognized by IgG auto-antibodies, forming immune complexes that are deposited in the kidneys, leading to glomerulonephritis. In the intestinal microbiota of patients with IgA nephropathy, there was increased relative abundance of mucin-degrading bacteria, including Akkermansia muciniphila. IgA1 was deglycosylated by A. muciniphila both in vitro and in the intestinal lumen of mice. This generated neo-epitopes that were recognized by autoreactive IgG from the sera of patients with IgA nephropathy. Mice expressing human IgA1 and the human Fc α receptor I (α1KI-CD89tg) that underwent intestinal colonization by A. muciniphila developed an aggravated IgA nephropathy phenotype. After deglycosylation of IgA1 by A. muciniphila in the mouse gut lumen, IgA1 crossed the intestinal epithelium into the circulation by retrotranscytosis and became deposited in the glomeruli of mouse kidneys. Human α-defensins-a risk locus for IgA nephropathy-inhibited growth of A. muciniphila in vitro. A negative correlation observed between stool concentration of α-defensin 6 and quantity of A. muciniphila in the guts of control participants was lost in patients with IgA nephropathy. This study demonstrates that gut microbiota dysbiosis contributes to generation of auto-antigens in patients with IgA nephropathy and in a mouse model of this disease.
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Microbioma Gastrointestinal , Glomerulonefritis por IGA , Humanos , Ratones , Animales , Inmunoglobulina A , Glomerulonefritis por IGA/genética , Riñón , Inmunoglobulina GRESUMEN
Wearable biosensors (wearables) enable continual, noninvasive physiologic and behavioral monitoring at home for those with pediatric or congenital heart disease. Wearables allow patients to access their personal data and monitor their health. Despite substantial technologic advances in recent years, issues with hardware design, data analysis, and integration into the clinical workflow prevent wearables from reaching their potential in high-risk congenital heart disease populations. This science advisory reviews the use of wearables in patients with congenital heart disease, how to improve these technologies for clinicians and patients, and ethical and regulatory considerations. Challenges related to the use of wearables are common to every clinical setting, but specific topics for consideration in congenital heart disease are highlighted.
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American Heart Association , Técnicas Biosensibles , Cardiopatías Congénitas , Dispositivos Electrónicos Vestibles , Humanos , Cardiopatías Congénitas/diagnóstico , Técnicas Biosensibles/instrumentación , Estados UnidosRESUMEN
OBJECTIVES: Patient priorities care (PPC) is an evidence-based approach designed to help patients achieve what matters most to them by identifying their health priorities and working with clinicians to align the care they provide to the patient's priorities. This study examined the impact of the PPC approach on long-term service and support (LTSS) use among veterans. DESIGN: Quasi-experimental study examining differences in LTSS use between veterans exposed to PPC and propensity-matched controls not exposed to PPC adjusting for covariates. SETTING AND PARTICIPANTS: Fifty-six social workers in 5 Veterans Health Administration (VHA) sites trained in PPC in 2018, 143 veterans who used the PPC approach, and 286 matched veterans who did not use the PPC approach. METHODS: Veterans with health priorities identified through the PPC approach were the intervention group (n = 143). The usual care group included propensity-matched veterans evaluated by the same social workers in the same period who did not participate in PPC (n = 286). The visit with the social worker was the index date. We examined LTSS use, emergency department (ED), and urgent care visits, 12 months before and after this date for both groups. Electronic medical record notes were extracted with a validated natural language processing algorithm (84% sensitivity, 95% specificity, and 92% accuracy). RESULTS: Most participants were white men, mean age was 76, and 30% were frail. LTSS use was 48% higher in the PPC group compared with the usual care group [odds ratio (OR), 1.48; 95% CI, 1.00-2.18; P = .05]. Among those who lived >2 years after the index date, new LTSS use was higher (OR, 1.69; 95% CI, 1.04-2.76; P = .036). Among nonfrail individuals, LTSS use was also higher in the PPC group (OR, 1.70; 95% CI, 1.06-2.74; P = .028). PPC was not associated with higher ED or urgent care use. CONCLUSIONS AND IMPLICATIONS: PPC results in higher LTSS use but not ED or urgent care in these veterans. LTSS use was higher for nonfrail veterans and those living longer. The PPC approach helps identify health priorities, including unmet needs for safe and independent living that LTSS can support.
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Puntaje de Propensión , Humanos , Masculino , Femenino , Estados Unidos , Anciano , Persona de Mediana Edad , Estudios de Cohortes , Veteranos , Prioridades en Salud , United States Department of Veterans Affairs , Cuidados a Largo PlazoRESUMEN
BACKGROUND: This study sought to evaluate the impact of elexacaftor-tezacaftor-ivacaftor (ETI) on lung structural abnormalities in adults with cystic fibrosis (awCF) with a specific focus on the reversal of bronchial dilatations. METHODS: Chest computed tomography (CT) performed prior to, and ≥12â months after initiation of ETI were visually reviewed for possible reversal of bronchial dilatations. AwCF with and without reversal of bronchial dilatation (the latter served as controls with 3 controls per case) were selected. Visual Brody score, bronchial and arterial diameters, and lung volume were measured on CT. RESULTS: Reversal of bronchial dilatation was found in 12/235 (5%) awCF treated with ETI. Twelve awCF with and 36 without reversal of bronchial dilatations were further analyzed (male=56%, mean age=31.6±8.5â years, F508del/F508del CFTR =54% and mean %predicted forced expiratory volume in 1â s=58.8%±22.3). The mean±sd Brody score improved overall from 79.4±29.8 to 54.8±32.3 (p<0.001). Reversal of bronchial dilatations was confirmed by a decrease in bronchial lumen diameter in cases from 3.9±0.9â mm to 3.2±1.1â mm (p<0.001), whereas it increased in awCF without reversal of bronchial dilatation (from 3.5±1.1â mm to 3.6±1.2â mm, p=0.002). Reversal of bronchial dilatations occurred in cylindrical (not varicose or saccular) bronchial dilatations. Lung volumes decreased by -6.6±10.7% in awCF with reversal of bronchial dilatation but increased by +2.3±9.6% in controls (p=0.007). CONCLUSION: Although bronchial dilatations are generally considered irreversible, ETI was associated with reversal, which was limited to the cylindrical bronchial dilatations subtype, and occurred in a small subset of awCF. Initiating ETI earlier in life may reverse early bronchial dilatations.
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Direct-to-consumer (D2C) wearables are becoming increasingly popular in cardiovascular health management because of their affordability and capability to capture diverse health data. Wearables may enable continuous health care provider-patient partnerships and reduce the volume of episodic clinic-based care (thereby reducing health care costs). However, challenges arise from the unregulated use of these devices, including questionable data reliability, potential misinterpretation of information, unintended psychological impacts, and an influx of clinically nonactionable data that may overburden the health care system. Further, these technologies could exacerbate, rather than mitigate, health disparities. Experience with wearables in atrial fibrillation underscores these challenges. The prevalent use of D2C wearables necessitates a collaborative approach among stakeholders to ensure effective integration into cardiovascular care. Wearables are heralding innovative disease screening, diagnosis, and management paradigms, expanding therapeutic avenues, and anchoring personalized medicine.
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Costos de la Atención en Salud , Humanos , Reproducibilidad de los ResultadosRESUMEN
The American Heart Association sponsored the first iteration of a scientific statement that addressed all aspects of cardiovascular implantable electronic device infection in 2010. Major advances in the prevention, diagnosis, and management of these infections have occurred since then, necessitating a scientific statement update. An 11-member writing group was identified and included recognized experts in cardiology and infectious diseases, with a career focus on cardiovascular infections. The group initially met in October 2022 to develop a scientific statement that was drafted with front-line clinicians in mind and focused on providing updated clinical information to enhance outcomes of patients with cardiovascular implantable electronic device infection. The current scientific statement highlights recent advances in prevention, diagnosis, and management, and how they may be incorporated in the complex care of patients with cardiovascular implantable electronic device infection.
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Cardiología , Infecciones Cardiovasculares , Enfermedades Transmisibles , Desfibriladores Implantables , Endocarditis Bacteriana , Estados Unidos , Humanos , American Heart Association , Enfermedades Transmisibles/diagnóstico , Enfermedades Transmisibles/epidemiología , Enfermedades Transmisibles/terapia , Endocarditis Bacteriana/tratamiento farmacológico , Desfibriladores Implantables/efectos adversosRESUMEN
A esporotricose é uma zoonose micótica emergente e subcutânea, que afeta a pele, o sistema linfático e outros órgãos de humanos e animais. Assim como outras doenças infecciosas fúngicas, se torna ainda mais grave quando acomete pacientes imunossuprimidos. Essa infecção possui distribuição global e é endêmica em algumas regiões do Brasil e de outros países tropicais e subtropicais, sendo um problema de saúde pública importante em nosso país. A doença é causada por um complexo de pelo menos quatro espécies patogênicas, incluindo o Sporothrix brasiliensis (S. brasiliensis). A resposta imunológica contra estas espécies ainda não é completamente elucidada, mas estruturas como as vesículas extracelulares (VEs) poderiam transportar componentes importantes que podem contribuir na modulação e no controle desta importante infecção. Assim, o objetivo deste trabalho, é analisar a participação das VEs de células dendríticas (DCs) naive e VEs de DCs previamente primadas com leveduras de S. brasiliensis e primadas com VEs do fungo, na resposta imune contra a esporotricose experimental em modelos murinos. Para isso, as DCs obtidas da medula óssea de camundongos, foram cultivadas com leveduras de S. brasiliensis ou com VEs do fungo e posteriormente, VEs totais das DCs foram purificadas a partir de ultracentrifugação e analisadas quanto a sua participação na modulação da resposta imunológica. Essas VEs foram utilizadas em protocolo profilático em modelos murinos, previamente a infecção subcutânea experimental. Foi observado o diâmetro médio das lesões no decorrer de 35 dias de infecção e a carga fúngica da lesão na pele. Os resultados obtidos mostram que as VEs de DCs naive, e VEs de DCs previamente cultivadas com leveduras do fungo ou com VEs fúngicas, são capazes de modular a carga fúngica. Os grupos que receberam VEs de DCs de forma profilática, de modo geral apresentaram diminuição significativa da carga fúngica em relação ao grupo controle. Na análise comparativa apenas dos grupos que receberam a profilaxia, observa-se que o uso de VEs de DCs naive, resultam em uma carga fúngica maior que o uso de VEs de DCs previamente ativadas, e quando as DCs são ativadas com levedura, essa carga fúngica é a menor. Quando analisamos o perfil de citocinas na pele de camundongos tratados com as VEs previamente a infecção, observamos aumento de IFN-γ, TNF-α, IL-17 e IL-10 principalmente nos animais previamente tratados com VEs de DCs que foram ativadas com leveduras. Em relação às citocinas produzidas, podemos sugerir até o momento, uma resposta imunológica mista, mas que de alguma maneira, ainda não esclarecida, devem contribuir para melhor controle do processo infeccioso in vivo. Em relação a linfoproliferação, observa-se principalmente um aumento de linfócitos T CD4+ quando acrescentamos VEs de DCs que não foram previamente ativadas, mostrando uma ação de uma resposta mais inespecífica. Vale ressaltar que todos os protocolos profiláticos foram capazes de modular e minimizar o crescimento fúngico, quando comparados ao controle, ou seja, as VEs contribuíram com o controle da infecção e agiram a favor do hospedeiro, demonstrando um caráter protetivo
Sporotrichosis is an emerging subcutaneous mycotic zoonosis that affects the skin, lymphatic system, and other organs of humans and animals, and like other infectious fungal diseases, it becomes even more serious when it affects immunosuppressed patients. This infection has a global distribution and is endemic in some regions of Brazil and other tropicals and subtropicals countries, being an important public health problem in our country. The disease is caused by a complex of at least four pathogenic species, including Sporothrix brasiliensis (S. brasiliensis). The immunological response against these species has not yet been completely elucidated, but structures such as extracellular vesicles (EVs) could carry important components that can contribute to the modulation and control of this important infection. Thus, the objective of this work is to analyze the participation of EVs from naïve dendritic cells (DCs) and EVs from DCs previously primed with S. brasiliensis yeast and primed with EVs from the fungus, in the immune response against experimental sporotrichosis in murine models. For this, DCs obtained from the bone marrow of mice were cultivated with S. brasiliensis yeast or EVs from the fungus, and subsequently, total EVs from the DCs were purified through ultracentrifugation and analyzed for their participation in modulating the immune response. These EVs were used in a prophylactic protocol in murine models, before experimental subcutaneous infection. The average diameter of the lesions over 35 days of infection and the fungal load of the lesion on the skin were observed. The results obtained show that EVs from naïve DCs, and EVs from DCs previously cultured with yeast or fungal EVs, are capable of modulating the fungal load. The groups that received EVs from DCs prophylactically generally showed a significant decrease in fungal load compared to the control group. In the comparative analysis of only the groups that received prophylaxis, it was observed that the use of EVs from naïve DCs results in a higher fungal load than the use of EVs from previously activated DCs, and when the DCs are activated with yeast, this load fungal is smaller. When we analyzed the cytokine profile in the skin of mice treated with EVs before infection, we observed an increase in IFN-γ, TNF-α, IL-17, and IL-10, mainly in animals previously treated with EVs from DCs that were activated with yeast. About the cytokines produced, we can so far suggest a mixed immunological response, but in some way, not yet clear, they should contribute to better control of the infectious process in vivo. About lymphoproliferation, an increase in CD4+ T lymphocytes is mainly observed when we add EVs from DCs that were not previously activated, showing a more nonspecific response. It is worth highlighting that all prophylactic protocols were able to modulate and minimize fungal growth, when compared to the control, that is, EVs contributed to the control of the infection and acted in favor of the host, demonstrating a protective character
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Esporotricosis/patología , Células Dendríticas/clasificación , Heridas y Lesiones/clasificación , Enfermedades Transmisibles/complicaciones , Vesículas Extracelulares/clasificaciónRESUMEN
BACKGROUND: Secondary bacterial infection (SBI) occurs in a proportion of individuals with dengue and results in longer hospitalization, higher mortality, and increased health-related costs. However, the frequency, risk factors and predictive biomarkers of this comorbidity in pediatric dengue is partially known. METHODS: We conducted a retrospective multicenter study in a dengue hyperendemic region of Colombia, analyzing 1597 children from two pediatric cohorts. We included children with confirmed dengue (mild to severe disease) and evaluated the rate of SBI, their clinical characteristics, diagnostic predictors and attention costs. We also assessed the diagnostic performance of plasma interleukin (IL)-6 for detecting SBI in pediatric dengue. RESULTS: The frequency of SBI in children with dengue with warning signs in cohorts 1 and 2 was 2.4% and 7.3%, respectively, and this rate reached 30.7% and 38.2% in children with severe disease. Staphylococcus aureus and Escherichia coli were the more frequent infectious agents. Increased total leukocytes and C-reactive protein levels, as well as high IL-6 at hospital admission, in children <48 months of age were early indications of SBI in dengue. Higher rates of organ dysfunction, the requirement of a longer hospitalization and a 2.3-fold increase in attention costs were observed in SBI. CONCLUSIONS: An important proportion of children with dengue course with SBI and exhibit higher morbidity. Elevated leukocytes, C-reactive protein and IL-6 in young children are early markers of SBI. Physicians should identify children with dengue and risk factors for SBI, microbiologically confirm the bacterial infection, and rationally and timely provide antimicrobial therapy.