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1.
Cytokine ; 133: 155135, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32534356

RESUMO

The anti-tuberculosis vaccine Bacillus Calmette-Guérin (BCG) is able to boost innate immune responses through a process called 'trained immunity'. It is hypothesized that BCG-induced trained immunity contributes to protection against Mycobacterium tuberculosis infection. Since alveolar macrophages are the first cell type to encounter M. tuberculosis upon infection, we aimed to investigate the immunomodulatory effects of BCG vaccination on alveolar macrophages. Searching for a less-invasive method than bronchoalveolar lavage, we optimized the isolation of alveolar macrophages from induced sputum of healthy volunteers. Viable alveolar macrophages could be successfully isolated from induced sputum and showed signs of activation already upon retrieval. Further flow cytometric analyses revealed that at baseline, higher expression levels of activation markers were observed on the alveolar macrophages of smokers compared to non-smokers. In addition, BCG vaccination resulted in decreased expression of the activation markers CD11b and HLA-DR on alveolar macrophages. Future studies should evaluate the functional consequences of this reduced activation of alveolar macrophages after BCG vaccination.


Assuntos
Vacina BCG/imunologia , Macrófagos Alveolares/imunologia , Escarro/imunologia , Adolescente , Adulto , Voluntários Saudáveis , Humanos , Imunidade Inata/imunologia , Fatores Imunológicos/imunologia , Masculino , Mycobacterium tuberculosis/imunologia , Tuberculose/imunologia , Vacinação/métodos , Adulto Jovem
2.
Genesis ; 54(8): 415-30, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27265328

RESUMO

Embryonic dermal fibroblasts in the skin have the exceptional ability to initiate hair follicle morphogenesis and contribute to scarless wound healing. Activation of the Wnt signaling pathway is critical for dermal fibroblast fate selection and hair follicle induction. In humans, mutations in Wnt pathway components and target genes lead to congenital focal dermal hypoplasias with diminished hair. The gene expression signature of embryonic dermal fibroblasts during differentiation and its dependence on Wnt signaling is unknown. Here we applied Shannon entropy analysis to identify the gene expression signature of mouse embryonic dermal fibroblasts. We used available human DNase-seq and histone modification ChiP-seq data on various cell-types to demonstrate that genes in the fibroblast cell identity signature can be epigenetically repressed in other cell-types. We found a subset of the signature genes whose expression is dependent on Wnt/ß-catenin activity in vivo. With our approach, we have defined and validated a statistically derived gene expression signature that may mediate dermal fibroblast identity and function in development and disease. genesis 54:415-430, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Diferenciação Celular , Derme/citologia , Fibroblastos/metabolismo , Transcriptoma , Via de Sinalização Wnt/genética , Animais , Derme/embriologia , Fibroblastos/citologia , Regulação da Expressão Gênica no Desenvolvimento , Camundongos
3.
Artigo em Inglês | MEDLINE | ID: mdl-39167447

RESUMO

BACKGROUND: Plasma cystatin C is a reliable marker to estimate kidney function; however, it is unknown whether this remains true in patients receiving continuous kidney replacement therapy (CKRT). Herein, we tested the hypothesis that lower concentrations of plasma cystatin C during the first three days of CKRT would predict kidney function recovery. METHODS: We performed a retrospective observational study of 72 patients from a 126-patient, single-center CKRT study. We studied two a priori defined cohorts of patients without advanced CKD who had acute kidney injury requiring CKRT (AKI-CKRT): 1) with early kidney function recovery defined as liberation from KRT within seven days of CKRT initiation versus 2) with delayed kidney function recovery defined as receipt of KRT for >21 days or death while on KRT. Subsequent analysis included patients with advanced CKD and intermediate kidney function recovery (liberation between 8 and 21 days). Cystatin C was then measured on stored plasma, urine, and dialysis effluent collected prior to CKRT initiation and on days 1, 2, and 3 of CKRT. RESULTS: Plasma cystatin C was significantly lower in patients with early kidney function recovery in comparison to patients with delayed kidney function recovery on days 1 (1.79 vs. 2.39mg/L), 2 (1.91 vs. 2.38mg/L) and 3 (2.04 vs. 2.67mg/L) of CKRT. Sieving coefficient and CKRT clearance of cystatin C were similar for patients with early and delayed kidney function recovery. The lowest plasma cystatin C concentration on days 1-3 of CKRT predicted early kidney function recovery with an area under the receiver operating curve of 0.77 (P = 0.002), positive likelihood ratio of 5.60 for plasma cystatin C <1.30mg/L, and negative likelihood ratio of 0.17 for plasma cystatin C ≥1.88mg/L. CONCLUSION: Lower plasma cystatin C concentrations during the first three days of CKRT are associated with early kidney function recovery.

4.
Crit Care Explor ; 4(12): e0816, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36601564

RESUMO

Distributive shock is a major cause of morbidity and mortality in the ICU. IV fluid resuscitation is a vital intervention to improve cardiac output and end-organ perfusion during the initial resuscitation and for those who remain fluid responsive. Noninvasive measures of fluid responsiveness are lacking. The aim of this study is to assess whether changes in end-tidal co2 after mini-fluid challenge, or 250 mL bolus, can predict fluid responsiveness in mechanically ventilated patients with distributive shock. DESIGN: Single-center prospective study. SETTING: Patients were enrolled from 2019 to 2021 from the medical ICU within a single academic hospital. PATIENTS: Thirty-eight patients with paired measurements of fluid responsiveness as determined by bioreactance who were admitted to the ICU with a diagnosis of distributive shock and on mechanical ventilation. INTERVENTIONS: Stroke volume index (SVI), cardiac index, heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, and ETco2 were measured before and after completion of a mini-fluid challenge. Test characteristics of change in ETco2 (ΔETco2) greater than or equal to 2 after mini-fluid challenge to determine fluid responsiveness were calculated with percentage change in SVI greater than or equal to 10% used as the reference standard. MEASUREMENTS AND MAIN RESULTS: The sensitivity and specificity of a ΔETco2 greater than or equal to 2 mm Hg as a predictor of a change in SVI greater than or equal to 10% following a mini-fluid challenge were 20.0% and 91.3%, respectively. The area under the receiver operating characteristic curve was 0.62. CONCLUSIONS: A ΔETco2 greater than or equal to 2 mm Hg after mini-fluid challenge has limited test performance for determining fluid responsiveness in intubated patients with distributive shock.

5.
Thromb Haemost ; 121(10): 1317-1325, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33450778

RESUMO

BACKGROUND: Fibrinogen (FIB) levels less than 150 mg/dL have been associated with increased rates of bleeding and lower survival in critically ill cirrhosis patients. OBJECTIVE: We aimed to determine if treatment with cryoprecipitate (CRYO) for low FIB levels is associated with bleeding outcomes or survival. METHODS: A total of 237 cirrhosis patients admitted to an intensive care unit at a tertiary care liver transplant center with initial FIB levels less than 150 mg/dL were retrospectively assessed for CRYO transfusion, bleeding events, and survival outcomes. RESULTS: The mean MELD score was 27.2 (95% confidence interval [CI]: 26.0-28.3) and CLIF-C acute on chronic liver failure score was 53.4 (51.9-54.8). Ninety-nine (41.8%) were admitted for acute bleeding and the remainder were admitted for nonbleeding illnesses. FIB level on admission correlated strongly with disease severity. After adjusting for disease severity, FIB on admission was not an independent predictor of 30-day survival (hazard ratio [HR]: 0.99, 95% CI: 0.99-1.01, p = 0.68). CRYO transfusion increased FIB levels but had no independent effect on mortality or bleeding complications (HR: 1.10, 95% CI: 0.72-1.70, p = 0.65). CONCLUSION: In cirrhosis patients with critical illness, low FIB levels on presentation reflect severity of illness but are not independently associated with 30-day mortality. Treatment of low FIB with CRYO also does not affect survival or bleeding complications, suggesting FIB is an additional marker of severity of illness but is not itself a direct factor in the pathophysiology of bleeding in critically ill cirrhosis patients.


Assuntos
Afibrinogenemia/terapia , Transfusão de Sangue , Varizes Esofágicas e Gástricas/terapia , Fator VIII/administração & dosagem , Fibrinogênio/metabolismo , Hemorragia Gastrointestinal/terapia , Hipertensão Portal/terapia , Cirrose Hepática/terapia , Afibrinogenemia/sangue , Afibrinogenemia/diagnóstico , Afibrinogenemia/mortalidade , Biomarcadores/sangue , Transfusão de Sangue/mortalidade , Estado Terminal , Regulação para Baixo , Varizes Esofágicas e Gástricas/sangue , Varizes Esofágicas e Gástricas/diagnóstico , Varizes Esofágicas e Gástricas/mortalidade , Fator VIII/efeitos adversos , Feminino , Fibrinogênio/administração & dosagem , Fibrinogênio/efeitos adversos , Hemorragia Gastrointestinal/sangue , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/mortalidade , Humanos , Hipertensão Portal/sangue , Hipertensão Portal/diagnóstico , Hipertensão Portal/mortalidade , Unidades de Terapia Intensiva , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
6.
ATS Sch ; 2(3): 484-496, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34667995

RESUMO

The American Thoracic Society Sleep Core Curriculum updates clinicians on important sleep topics, presented during the annual meeting, and appearing in summary here. This year's sleep core theme is sleep-disordered breathing and its management. Topics range from pathophysiological mechanisms for the association of obstructive sleep apnea (OSA) and metabolic syndrome, surgical modalities of OSA treatment, comorbid insomnia and OSA, central sleep apnea, and sleep practices during a pandemic. OSA has been associated with metabolic syndrome, independent of the role of obesity, and the pathophysiology suggests a role for sleep fragmentation and intermittent hypoxia in observed metabolic outcomes. In specific patient populations, surgical treatment modalities for OSA have demonstrated large reductions in objective disease severity compared with no treatment and may facilitate adherence to positive airway pressure treatment. Patient-centered approaches to comorbid insomnia and sleep apnea include evaluating for both OSA and insomnia simultaneously and using shared-decision making to determine the order and timing of positive airway pressure therapy and cognitive behavioral therapy for insomnia. The pathophysiology of central sleep apnea is complex and may be due to the loss of drive to breathe or instability in the regulatory pathways that control ventilation. Pandemic-era sleep practices have evolved rapidly to balance safety and sustainability of care for patients with sleep-disordered breathing.

7.
JAMA Intern Med ; 183(4): 360-361, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36780155

RESUMO

This Teachable Moment discusses time-limited trials, "an agreement between clinicians and a patient/family to use certain medical therapies over a defined period to see if the patient improves or deteriorates according to agreed-on clinical outcomes.".


Assuntos
Cuidados Críticos , Unidades de Terapia Intensiva , Humanos , Fatores de Tempo
8.
Biomed Res Int ; 2018: 5051289, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29850526

RESUMO

BACKGROUND: Cardiovascular disease (CVD) annually claims more lives and costs more dollars than any other disease globally amid widening health disparities, despite the known significant reductions in this burden by low cost dietary changes. The world's first medical school-based teaching kitchen therefore launched CHOP-Medical Students as the largest known multisite cohort study of hands-on cooking and nutrition education versus traditional curriculum for medical students. METHODS: This analysis provides a novel integration of artificial intelligence-based machine learning (ML) with causal inference statistics. 43 ML automated algorithms were tested, with the top performer compared to triply robust propensity score-adjusted multilevel mixed effects regression panel analysis of longitudinal data. Inverse-variance weighted fixed effects meta-analysis pooled the individual estimates for competencies. RESULTS: 3,248 unique medical trainees met study criteria from 20 medical schools nationally from August 1, 2012, to June 26, 2017, generating 4,026 completed validated surveys. ML analysis produced similar results to the causal inference statistics based on root mean squared error and accuracy. Hands-on cooking and nutrition education compared to traditional medical school curriculum significantly improved student competencies (OR 2.14, 95% CI 2.00-2.28, p < 0.001) and MedDiet adherence (OR 1.40, 95% CI 1.07-1.84, p = 0.015), while reducing trainees' soft drink consumption (OR 0.56, 95% CI 0.37-0.85, p = 0.007). Overall improved competencies were demonstrated from the initial study site through the scale-up of the intervention to 10 sites nationally (p < 0.001). DISCUSSION: This study provides the first machine learning-augmented causal inference analysis of a multisite cohort showing hands-on cooking and nutrition education for medical trainees improves their competencies counseling patients on nutrition, while improving students' own diets. This study suggests that the public health and medical sectors can unite population health management and precision medicine for a sustainable model of next-generation health systems providing effective, equitable, accessible care beginning with reversing the CVD epidemic.


Assuntos
Cardiologia/educação , Culinária , Currículo , Educação em Saúde , Aprendizado de Máquina , Análise Multinível , Pontuação de Propensão , Estudantes de Medicina , Adulto , Estudos de Coortes , Educação Médica , Feminino , Humanos , Masculino , Fenômenos Fisiológicos da Nutrição
10.
J Interferon Cytokine Res ; 35(8): 585-99, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25803788

RESUMO

Granulocyte macrophage colony stimulating factor (GM-CSF) is generally recognized as an inflammatory cytokine. Its inflammatory activity is primarily due its role as a growth and differentiation factor for granulocyte and macrophage populations. In this capacity, among other clinical applications, it has been used to bolster anti-tumor immune responses. GM-CSF-mediated inflammation has also been implicated in certain types of autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. Thus, agents that can block GM-CSF or its receptor have been used as anti-inflammatory therapies. However, a review of literature reveals that in many situations GM-CSF can act as an anti-inflammatory/regulatory cytokine. We and others have shown that GM-CSF can modulate dendritic cell differentiation to render them "tolerogenic," which, in turn, can increase regulatory T-cell numbers and function. Therefore, the pro-inflammatory and regulatory effects of GM-CSF appear to depend on the dose and the presence of other relevant cytokines in the context of an immune response. A thorough understanding of the various immunomodulatory effects of GM-CSF will facilitate more appropriate use and thus further enhance its clinical utility.


Assuntos
Citocinas/fisiologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/fisiologia , Mediadores da Inflamação/fisiologia , Animais , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Autoimunidade , Citocinas/farmacologia , Citocinas/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Humanos , Tolerância Imunológica , Imunossupressores/metabolismo , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Imunoterapia , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/metabolismo , Mediadores da Inflamação/farmacologia , Mediadores da Inflamação/uso terapêutico
11.
Am J Orthop (Belle Mead NJ) ; 40(11): 576-8, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22263211

RESUMO

Calcific periarthritis is a calcium deposition disease of the periarticular tissues. Deposits of calcium from calcific periarthritis can be found in the periarticular tissues of the shoulders, hips, elbows, wrists, and knees. This disease is often the manifestation of another primary process, such as end-stage renal disease, collagen vascular disease, and systemic diseases (eg, diabetes mellitus, rheumatoid arthritis), among others. Furthermore, calcific periarthritis has been linked to certain areas of the body because of pathologic stress related to repetitive motions, microtrauma, and local hypoxia. This type of soft-tissue mass is usually found in older men and women. In addition, its incidence, calcium deposits related to calcific periarthritis, and soft-tissue masses in general, are rare in children. Here we present the first report of idiopathic chronic calcific periarthritis in a child. The diagnosis was suspected on the basis of clinical and radiographic appearance and despite the rarity of the disease in children. The patient underwent surgical treatment and was free of local recurrence. The cause of this case was never determined.


Assuntos
Calcinose/diagnóstico por imagem , Articulação do Cotovelo/diagnóstico por imagem , Periartrite/diagnóstico por imagem , Calcinose/patologia , Calcinose/cirurgia , Criança , Articulação do Cotovelo/patologia , Articulação do Cotovelo/cirurgia , Feminino , Humanos , Periartrite/patologia , Periartrite/cirurgia , Radiografia , Resultado do Tratamento
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