RESUMO
BACKGROUND: Research suggests demographic, economic, residential, and health-related factors influence vulnerability to environmental exposures. Greater environmental vulnerability may exacerbate environmentally related health outcomes. We developed a neighborhood environmental vulnerability index (NEVI) to operationalize environmental vulnerability on a neighborhood level. OBJECTIVE: We explored the relationship between NEVI and pediatric asthma emergency department (ED) visits (2014-19) in 3 US metropolitan areas: Los Angeles County, Calif; Fulton County, Ga; and New York City, NY. METHODS: We performed separate linear regression analyses examining the association between overall NEVI score and domain-specific NEVI scores (demographic, economic, residential, health status) with pediatric asthma ED visits (per 10,000) across each area. RESULTS: Linear regression analyses suggest that higher overall and domain-specific NEVI scores were associated with higher annual pediatric asthma ED visits. Adjusted R2 values suggest that overall NEVI scores explained at least 40% of the variance in pediatric asthma ED visits. Overall NEVI scores explained more of the variance in pediatric asthma ED visits in Fulton County. NEVI scores for the demographic, economic, and health status domains explained more of the variance in pediatric asthma ED visits in each area compared to the NEVI score for the residential domain. CONCLUSION: Greater neighborhood environmental vulnerability was associated with greater pediatric asthma ED visits in each area. The relationship differed in effect size and variance explained across the areas. Future studies can use NEVI to identify populations in need of greater resources to mitigate the severity of environmentally related outcomes, such as pediatric asthma.
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Asma , Nevo , Criança , Humanos , Asma/epidemiologia , Morbidade , Serviço Hospitalar de Emergência , Características de ResidênciaRESUMO
INTRODUCTION: There is a paucity of literature comparing patients receiving bedside placed percutaneous endoscopic gastrostomy (PEG) versus fluoroscopic-guided percutaneous gastrostomy tubes (G-tube) in an intensive care unit (ICU) setting. This study aims to investigate and compare the natural history and complications associated with PEG versus fluoroscopic G-tube placement in ICU patients. METHODS: All adult patients admitted in the ICU requiring feeding tube placement at our center from 1/1/2017 to 1/1/2022 with at least 12-month follow up were identified through retrospective chart review. Adjusting for patient comorbidities, hospital factors, and indications for enteral access, a 1-to-2 propensity score matched Cox proportional-hazards model was fitted to evaluate the treatment effect of bedside PEG tube placement versus G-tube placement on patient 1-year complication, readmission, and death rates. Major complications were defined as those requiring operative or procedural intervention. RESULTS: This study included 740 patients, with 178 bedside PEG and 562 fluoroscopic G-tube placements. The overall rate of complication was 22.3% (13% PEG, 25.2% G-tube, P = 0.003). The major complication rate was 11.2% (8.5% PEG, 12.1% G-tube, P = 0.09). Most common complications were tube dysfunction (16.7% PEG; 39.4% G-tube; P = 0.04) and dislodgement (58.3% PEG; 40.8% G-tube). After propensity score matching, G-tube recipients had significantly increased risk for all-cause (HR 2.7, 95% CI 1.56-4.87, P < 0.001) and major complications (HR 2.11, 95% CI 1.05-4.23, P = 0.035). There were no significant differences in 1-year rates of readmission (HR 0.90, 95% CI 0.58-1.38, P = 0.62) or death (HR 1.00, 95% CI 0.70-1.44, P = 0.7). CONCLUSIONS: The overall rate of complications for ICU patients requiring feeding tube in our cohort was 22.3%. ICU patients receiving fluoroscopic-guided percutaneous gastrostomy tube placement had significantly elevated risk of 1-year all-cause and major complications compared to those undergoing bedside PEG.
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Gastrostomia , Unidades de Terapia Intensiva , Adulto , Humanos , Gastrostomia/efeitos adversos , Estudos Retrospectivos , Fluoroscopia , Fatores de RiscoRESUMO
OBJECTIVE: To investigate the relationship between frailty and treatment response to antidepressant medications in adults with late life depression (LLD). METHODS: Data were evaluated from 100 individuals over age 60 years (34 men, 66 women) with a depressive diagnosis, who were assessed for frailty at baseline (characteristics include gait speed, grip strength, activity levels, fatigue, and weight loss) and enrolled in an 8-week trial of antidepressant medication followed by 10 months of open-treatment. RESULTS: Frail individuals (nâ¯=â¯49 with ≥3 deficits in frailty characteristics) did not differ at baseline from the non/intermediate frail (nâ¯=â¯51 with 0-2 deficits) on demographic, medical comorbidity, cognitive, or depression variables. On average, frail individuals experienced 2.82 fewer Hamilton Rating Scale for Depression (HRSD) points of improvement (tâ¯=â¯2.12, df 89, p = 0.037) than the non/intermediate frail over acute treatment, with this difference persisting over 10 months of open-treatment. Weak grip strength and low physical activity levels were each associated with decreased HRSD improvement, and lower response and remission rates over the course of the study. Despite their poorer outcomes, frail individuals received more antidepressant medication trials than the non/intermediate frail. CONCLUSION: Adults with LLD and frailty have an attenuated response to antidepressant medication and a greater degree of disability compared to non/intermediate frail individuals. This disability and attenuated response remain even after receiving a greater number of antidepressant medication trials. Future research must focus on understanding the specific pathophysiology associated with the frail-depressed phenotype to permit the design and implementation of precision medicine interventions for this high-risk population.
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Fragilidade , Idoso , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Feminino , Idoso Fragilizado , Fragilidade/complicações , Fragilidade/tratamento farmacológico , Humanos , Masculino , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the rates of frailty and frailty characteristics and examine the clinical and neuropsychological correlates of frailty in adults with late life depression (LLD). METHODS: Data were used from the evaluation of 134 individuals over the age of 60 years (45 men, 89 women) with a depressive diagnosis who enrolled in studies for the treatment of their depression. Depression, neuropsychological functioning, white matter hyperintensity (WMH) burden via magnetic resonance imaging, and characteristics of frailty were assessed. RESULTS: Fried frailty burden (≥3 characteristics) was present in 25% of the sample, with this rate increasing to 45.5% when using clinically meaningful cut-scores for gait speed (<1 m/s) and physical activity levels (<1000 kcal/week). Moreover, 62% of the sample exhibited gait slowing (<1 m/s) or weakness (grip strength), with 29% demonstrating both. Greater frailty burden was associated with greater Hamilton Depression Rating Scale severity in covariate adjusted linear regression models (t127â¯=â¯2.41, pâ¯=â¯0.02). Greater frailty burden was not associated with neuropsychological dysfunction, nor was it associated with greater WMH burden. CONCLUSION: Findings from this study show that frailty, specifically physical frailty deficits in mobility and strength, is highly comorbid in adults with LLD, associated with greater depressive symptom severity, and does not appear to be associated with the vascular depression subtype of LLD. Future research should investigate the relationship between frailty and antidepressant treatment response as well as test whether there are age-related biological processes that result in the manifestation of the frail-depressed subtype of LLD.
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Depressão/fisiopatologia , Depressão/psicologia , Idoso Fragilizado/psicologia , Substância Branca/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Força da Mão , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Substância Branca/diagnóstico por imagemRESUMO
Dysregulation of the hepatic endocannabinoid (EC) system and high fat diet (HFD) are associated with non-alcoholic fatty liver disease. Liver cytosol contains high levels of two novel endocannabinoid binding proteins-liver fatty acid binding protein (FABP1) and sterol carrier protein-2 (SCP-2). While Fabp1 gene ablation significantly increases hepatic levels of arachidonic acid (ARA)-containing EC and sex-dependent response to pair-fed high fat diet (HFD), the presence of SCP-2 complicates interpretation. These issues were addressed by ablating Scp-2/Scp-x in Fabp1 null mice (TKO). In control-fed mice, TKO increased hepatic levels of arachidonoylethanolamide (AEA) in both sexes. HFD impacted hepatic EC levels by decreasing AEA in TKO females and decreasing 2-arachidonoyl glycerol (2-AG) in WT of both sexes. Only TKO males on HFD had increased hepatic 2-AG levels. Hepatic ARA levels were decreased in control-fed TKO of both sexes. Changes in hepatic AEA/2-AG levels were not associated with altered amounts of hepatic proteins involved in AEA/2-AG synthesis or degradation. These findings suggested that ablation of the Scp-2/Scp-x gene in Fabp1 null mice exacerbated hepatic EC accumulation and antagonized the impact of HFD on hepatic EC levels-suggesting both proteins play important roles in regulating the hepatic EC system.
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Proteínas de Transporte/genética , Dieta Hiperlipídica , Gorduras na Dieta/metabolismo , Endocanabinoides/metabolismo , Proteínas de Ligação a Ácido Graxo/genética , Fígado/metabolismo , Animais , Proteínas de Transporte/metabolismo , Proteínas de Ligação a Ácido Graxo/metabolismo , Feminino , Deleção de Genes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
Upregulation of the hepatic endocannabinoid (EC) receptor [cannabinoid receptor-1 (CB1)] and arachidonoylethanolamide (AEA) is associated with nonalcoholic fatty liver disease (NAFLD). Male mice fed high-fat diet (HFD) ad libitum also exhibit NAFLD, increased hepatic AEA, and obesity. But, preference for HFD complicates interpretation and almost nothing is known about these effects in females. These issues were addressed by pair-feeding HFD. Similarly to ad libitum-fed HFD, pair-fed HFD also increased WT male and female mouse fat tissue mass (FTM), but preferentially at the expense of lean tissue mass. In contrast, pair-fed HFD did not elicit NAFLD in WT mice regardless of sex. Concomitantly, pair-fed HFD oppositely impacted hepatic AEA, 2-arachidonoyl glycerol, and/or CB1 in WT males versus females. In pair-fed HFD mice, liver FA binding protein-1 (Fabp1) gene ablation (LKO): i) exacerbated FTM in both sexes; ii) did not elicit liver neutral lipid accumulation in males and only slightly in females; iii) increased liver AEA in males, but decreased it in females; and iv) decreased CB1 only in males. Thus, pair-fed HFD selectively impacted hepatic ECs more in females, but did not elicit NAFLD in either sex. These effects were modified by LKO consistent with FABP1's ability to impact EC and FA metabolism.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Endocanabinoides/metabolismo , Proteínas de Ligação a Ácido Graxo/deficiência , Proteínas de Ligação a Ácido Graxo/genética , Técnicas de Inativação de Genes , Fígado/efeitos dos fármacos , Fígado/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Transporte Biológico/genética , Biomarcadores/sangue , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Citosol/efeitos dos fármacos , Citosol/metabolismo , Ácidos Graxos/metabolismo , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/genética , Lipogênese/efeitos dos fármacos , Lipogênese/genética , Fígado/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Tamanho do Órgão/genética , Fenótipo , Proteína de Ligação a Elemento Regulador de Esterol 1/genéticaRESUMO
The endocannabinoid system shifts energy balance toward storage and fat accumulation, especially in the context of diet-induced obesity. Relatively little is known about factors outside the central nervous system that may mediate the effect of high-fat diet (HFD) on brain endocannabinoid levels. One candidate is the liver fatty acid binding protein (FABP1), a cytosolic protein highly prevalent in liver, but not detected in brain, which facilitates hepatic clearance of fatty acids. The impact of Fabp1 gene ablation (LKO) on the effect of high-fat diet (HFD) on brain and plasma endocannabinoid levels was examined and data expressed for each parameter as the ratio of high-fat diet/control diet. In male wild-type mice, HFD markedly increased brain N-acylethanolamides, but not 2-monoacylglycerols. LKO blocked these effects of HFD in male mice. In female wild-type mice, HFD slightly decreased or did not alter these endocannabinoids as compared with male wild type. LKO did not block the HFD effects in female mice. The HFD-induced increase in brain arachidonic acid-derived arachidonoylethanolamide in males correlated with increased brain-free and total arachidonic acid. The ability of LKO to block the HFD-induced increase in brain arachidonoylethanolamide correlated with reduced ability of HFD to increase brain-free and total arachidonic acid in males. In females, brain-free and total arachidonic acid levels were much less affected by either HFD or LKO in the context of HFD. These data showed that LKO markedly diminished the impact of HFD on brain endocannabinoid levels, especially in male mice.
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Encéfalo/metabolismo , Endocanabinoides/metabolismo , Metabolismo Energético/fisiologia , Proteínas de Ligação a Ácido Graxo/metabolismo , Animais , Ácidos Araquidônicos/farmacologia , Dieta Hiperlipídica , Endocanabinoides/farmacologia , Feminino , Resistência à Insulina/fisiologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Alcamidas Poli-Insaturadas/farmacologia , Receptor CB1 de Canabinoide/metabolismoRESUMO
Endocannabinoids (ECs) and cannabinoids are very lipophilic molecules requiring the presence of cytosolic binding proteins that chaperone these molecules to intracellular targets. While three different fatty acid binding proteins (FABP3, -5, and -7) serve this function in brain, relatively little is known about how such hydrophobic ECs and cannabinoids are transported within the liver. The most prominent hepatic FABP, liver fatty acid binding protein (FABP1 or L-FABP), has high affinity for arachidonic acid (ARA) and ARA-CoA, suggesting that FABP1 may also bind ARA-derived ECs (AEA and 2-AG). Indeed, FABP1 bound ECs with high affinity as shown by displacement of FABP1-bound fluorescent ligands and by quenching of FABP1 intrinsic tyrosine fluorescence. FABP1 also had high affinity for most non-ARA-containing ECs, FABP1 inhibitors, EC uptake/hydrolysis inhibitors, and phytocannabinoids and less so for synthetic cannabinoid receptor (CBR) agonists and antagonists. The physiological impact was examined with liver from wild-type (WT) versus FABP1 gene-ablated (LKO) male mice. As shown by liquid chromatography and mass spectrometry, FABP1 gene ablation significantly increased hepatic levels of AEA, 2-AG, and 2-OG. These increases were not due to increased protein levels of EC synthetic enzymes (NAPEPLD and DAGL) or a decreased level of EC degradative enzyme (FAAH) but correlated with complete loss of FABP1, a decreased level of SCP2 (8-fold less prevalent than FABP1, but also binds ECs), and a decreased level of degradative enzymes (NAAA and MAGL). These data indicated that FABP1 not only is the most prominent endocannabinoid and cannabinoid binding protein but also impacts hepatic endocannabinoid levels.
Assuntos
Endocanabinoides/metabolismo , Proteínas de Ligação a Ácido Graxo/metabolismo , Receptores de Canabinoides/metabolismo , Animais , Feminino , Corantes Fluorescentes , Humanos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Liver fatty acid-binding protein (FABP1, L-FABP) has high affinity for and enhances uptake of arachidonic acid (ARA, C20:4, n-6) which, when esterified to phospholipids, is the requisite precursor for synthesis of endocannabinoids (EC) such as arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG). The brain derives most of its ARA from plasma, taking up ARA and transporting it intracellularly via cytosolic fatty acid-binding proteins (FABPs 3,5, and 7) localized within the brain. In contrast, the much more prevalent cytosolic FABP1 is not detectable in the brain but is instead highly expressed in the liver. Therefore, the possibility that FABP1 outside the central nervous system may regulate brain AEA and 2-AG was examined in wild-type (WT) and FABP1 null (LKO) male mice. LKO increased brain levels of AA-containing EC (AEA, 2-AG), correlating with increased free and total ARA in brain and serum. LKO also increased brain levels of non-ARA that contain potentiating endocannabinoids (EC*) such as oleoyl ethanolamide (OEA), PEA, 2-OG, and 2-PG. Concomitantly, LKO decreased serum total ARA-containing EC, but not non-ARA endocannabinoids. LKO did not elicit these changes in the brain EC and EC* as a result of compensatory up-regulation of brain protein levels of enzymes in EC synthesis (NAPEPLD, DAGLα) or cytosolic EC chaperone proteins (FABPs 3, 5, 7, SCP-2, HSP70), or cannabinoid receptors (CB1, TRVP1). These data show for the first time that the non-CNS fatty acid-binding protein FABP1 markedly affected brain levels of both ARA-containing endocannabinoids (AEA, 2-AG) as well as their non-ARA potentiating endocannabinoids. Fatty acid-binding protein-1 (FABP-1) is not detectable in brain but instead is highly expressed in liver. The possibility that FABP1 outside the central nervous system may regulate brain endocannabinoids arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG) was examined in wild-type (WT) and FABP-1 null (LKO) male mice. LKO increased brain levels of arachidonic acid-containing endocannabinoids (AEA, 2-AG), correlating with increased free and total arachidonic acid in brain and serum. Read the Editorial Highlight for this article on page 371.
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Ácidos Araquidônicos/metabolismo , Encéfalo/metabolismo , Endocanabinoides/metabolismo , Proteínas de Ligação a Ácido Graxo/genética , Fígado/metabolismo , Ácidos Oleicos/metabolismo , Alcamidas Poli-Insaturadas/metabolismo , Animais , Ácidos Araquidônicos/genética , Encéfalo/efeitos dos fármacos , Endocanabinoides/genética , Glicerídeos/metabolismo , Fígado/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Camundongos KnockoutAssuntos
COVID-19 , SARS-CoV-2 , Vacinas contra COVID-19 , Humanos , Imunidade Celular , Rituximab , VacinaçãoRESUMO
Depression in later life is a severe public health problem, associated with higher rates of mortality, suicide, and dementia. Effectiveness of treatment is limited by the failure to deconstruct the heterogeneity of the illness and because diagnostic criteria, pathophysiological models, and treatment algorithms for depression are primarily based on studies of younger adults even though symptoms of the illness and physiology of the patient change with age. Thus, understanding how aging interacts with depressive illness may elucidate endophenotypes of late-life depression with different clinical manifestations and underlying mechanisms that can then be targeted with more personalized approaches to treatment. This paper proposes a model for the critical confluence between depression and frailty, a high-risk morbidity and mortality syndrome of later life. This model hypothesizes that characteristics of frailty in adults with late life depression represent the clinical manifestation of greater biological aging and their presence in the context of a depressive illness exposes elders to deleterious trajectories. Potential common biological substrates that may result in the manifestation of the depressed frail phenotype including mitochondrial functioning, dopaminergic neurotransmission, and inflammatory processes and implications for the assessment and treatment of adults with late-life depression are discussed. As society continues to live longer, the preservation of the quality of these added years becomes paramount, and the combined impact of depression and frailty on the preservation of this quality warrants the attention of clinical researchers and physicians.
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Envelhecimento/metabolismo , Transtorno Depressivo/metabolismo , Fragilidade/metabolismo , Envelhecimento/imunologia , Transtorno Depressivo/imunologia , Dopamina/metabolismo , Fragilidade/imunologia , Humanos , Inflamação , Mitocôndrias/metabolismo , Estresse Oxidativo , Fenótipo , Transmissão SinápticaRESUMO
BACKGROUND: Adverse drug reactions (ADRs) to antibiotics in patients with cystic fibrosis (CF) are common and often mislabeled as allergies. The labeling of an antibiotic reaction as an allergy can lead to the use of antibiotics that are less efficacious, are more expensive, or have a greater risk of adverse effects. OBJECTIVE: To establish a safe approach for the evaluation of ADRs to antibiotics in patients with CF to help clarify future use of these medications. METHODS: Patients with CF whose antibiotic allergies were causing difficulty in their medical management were referred for an allergy evaluation that consisted of a thorough drug allergy history and antibiotic testing if appropriate. If the history was not consistent with a true hypersensitivity reaction (HSR) and test results were negative, the patient underwent a challenge to the offending agent(s) to rule out an HSR. Challenges were only performed if the medication was indicated for future use. RESULTS: A total of 17 patients (mean age, 32.4 years) underwent a thorough allergy evaluation. A total of 17 antibiotic challenges were performed in 11 patients without a reaction consistent with an HSR or severe delayed reaction. Only 2 medications had a history consist with an HSR, and it was recommended that they undergo a desensitization procedure if the drug was required. CONCLUSION: If treatment with appropriate antibiotics becomes difficult in patients with CF because of drug allergies, then referral to an allergist can help safely identify treatment options. Our findings suggest that a thorough evaluation by an allergy specialist can lead to more appropriate treatment options in patients with CF.
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Antibacterianos/efeitos adversos , Fibrose Cística/tratamento farmacológico , Hipersensibilidade a Drogas/etiologia , Adulto , Hipersensibilidade a Drogas/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Cutâneos , Adulto JovemRESUMO
In this study, we characterized cerebral blood flow changes by assessment of blood flow parameters in neck arteries using carotid duplex ultrasonography and predictive factors for these hemodynamic changes. Hemodynamic variables were measured before and during hemodialysis in 81 patients with an arteriovenous access in their arm. Hemodialysis produced significant lowering in peak systolic velocity and flow volume of neck arteries and calculated total cerebral blood flow (1,221.9 ± 344.9 [before hemodialysis] vs. 1,085.8 ± 319.2 [during hemodialysis], P < 0.001). Effects were greater in vessels on the same side as the arteriovenous access and these changes were influenced by arteriovenous access flow during hemodialysis, both in the CCA (r = -0.277, P = 0.015) and the VA (r = -0.239, P = 0.034). The change of total cerebral blood flow during hemodialysis was independently related with age, presence of diabetes, and systemic blood pressure.
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Circulação Cerebrovascular/fisiologia , Hemodinâmica/fisiologia , Falência Renal Crônica/fisiopatologia , Idoso , Artérias Carótidas/diagnóstico por imagem , Tontura/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal , Fatores de Risco , Ultrassonografia Doppler DuplaRESUMO
In hemodialysis patients, vascular access infection remains a significant cause of morbidity and mortality. It has various complications, including bacterial endocarditis, spinal epidural abscess, osteomyelitis, septic arthritis, and septic pulmonary emboli. However, aortitis with infected pseudoaneurysm formation is very rare. Here, we report a case of necrotizing aortitis in a hemodialysis patient with an arteriovenous graft infection.
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Falso Aneurisma/patologia , Aortite/patologia , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Falso Aneurisma/microbiologia , Aorta Torácica/lesões , Aorta Torácica/patologia , Aortite/microbiologia , Evolução Fatal , Humanos , Falência Renal Crônica/microbiologia , Falência Renal Crônica/patologia , Masculino , Pessoa de Meia-Idade , Diálise Renal/métodos , Ruptura EspontâneaRESUMO
Adult-onset Still's disease (AOSD) is a rare autoinflammatory disorder with potential for life-threatening complications in pregnancy. Recently, biologic therapeutics have been increasingly used for treatment of AOSD, but there is little available data on the treatment of AOSD in pregnancy. Here we report a 23-year-old primigravid patient with a history of AOSD who presented at 20 weeks of gestation with fever, arthralgias, rash, fatigue, and highly elevated ferritin, concerning for AOSD flare. She was treated with tocilizumab, an interleukin-6 receptor antagonist, with rapid clinical and laboratory improvement; however, she underwent iatrogenic preterm delivery at 34 weeks of gestation for fetal distress, which was attributed to placental injury. In a subsequent pregnancy, she was treated with tocilizumab throughout and had an uncomplicated term delivery with normal labs and no AOSD flare. This case highlights that the use of tocilizumab may be effective to reduce the risk of AOSD flare during pregnancy.
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Doença de Still de Início Tardio , Adulto , Recém-Nascido , Humanos , Feminino , Gravidez , Adulto Jovem , Doença de Still de Início Tardio/complicações , Doença de Still de Início Tardio/diagnóstico , Doença de Still de Início Tardio/tratamento farmacológico , PlacentaRESUMO
The Caregiver Strain Questionnaire assesses the three dimensions of caregiver strain, namely the objective, subjective externalized and subjective internalized strain. It was validated among caregivers of children with Autism Spectrum Disorder (ASD) in the United States and Mainland China with promising psychometric properties.This study aimed to develop and validate the Chinese (traditional script) version of the Caregiver Strain Questionnaire (C-CGSQ) among 198 caregivers of children with ASD in Hong Kong. The C-CGSQ showed excellent internal consistency (α = 0.958) and test-retest reliability (Spearman's r = 0.966). Concurrent, convergent, divergent validity and a three-factor structure (consistent with previous studies) were established. The C-CGSQ demonstrated promising psychometric properties in measuring caregiver strain among caregivers of Chinese ASD children in Hong Kong.
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BACKGROUND: Management of immune-related adverse events (irAEs) is important as they cause treatment interruption or discontinuation, more often seen with combination immune checkpoint inhibitor (ICI) therapy. Here, we retrospectively evaluated the safety and effectiveness of anti-interleukin-6 receptor (anti-IL-6R) as therapy for irAEs. METHODS: We performed a retrospective multicenter study evaluating patients diagnosed with de novo irAEs or flare of pre-existing autoimmune disease following ICI and were treated with anti-IL-6R. Our objectives were to assess the improvement of irAEs as well as the overall tumor response rate (ORR) before and after anti-IL-6R treatment. RESULTS: We identified a total of 92 patients who received therapeutic anti-IL-6R antibodies (tocilizumab or sarilumab). Median age was 61 years, 63% were men, 69% received anti-programmed cell death protein-1 (PD-1) antibodies alone, and 26% patients were treated with the combination of anti-cytotoxic T lymphocyte antigen-4 and anti-PD-1 antibodies. Cancer types were primarily melanoma (46%), genitourinary cancer (35%), and lung cancer (8%). Indications for using anti-IL-6R antibodies included inflammatory arthritis (73%), hepatitis/cholangitis (7%), myositis/myocarditis/myasthenia gravis (5%), polymyalgia rheumatica (4%), and one patient each with autoimmune scleroderma, nephritis, colitis, pneumonitis and central nervous system vasculitis. Notably, 88% of patients had received corticosteroids, and 36% received other disease-modifying antirheumatic drugs (DMARDs) as first-line therapies, but without adequate improvement. After initiation of anti-IL-6R (as first-line or post-corticosteroids and DMARDs), 73% of patients showed resolution or change to ≤grade 1 of irAEs after a median of 2.0 months from initiation of anti-IL-6R therapy. Six patients (7%) stopped anti-IL-6R due to adverse events. Of 70 evaluable patients by RECIST (Response Evaluation Criteria in Solid Tumors) V.1.1 criteria; the ORR was 66% prior versus 66% after anti-IL-6R (95% CI, 54% to 77%), with 8% higher complete response rate. Of 34 evaluable patients with melanoma, the ORR was 56% prior and increased to 68% after anti-IL-6R (p=0.04). CONCLUSION: Targeting IL-6R could be an effective approach to treat several irAE types without hindering antitumor immunity. This study supports ongoing clinical trials evaluating the safety and efficacy of tocilizumab (anti-IL-6R antibody) in combination with ICIs (NCT04940299, NCT03999749).
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Antirreumáticos , Neoplasias Pulmonares , Melanoma , Receptores de Interleucina-6 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Corticosteroides/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Melanoma/tratamento farmacológico , Estudos Retrospectivos , Receptores de Interleucina-6/antagonistas & inibidoresRESUMO
Renal actinomycosis is a rare infection caused by fungi of the genus Actinomyces. A 74-year-old male was admitted to our hospital because of gross hematuria with urinary symptoms and intermittent chills. Computed tomography of the abdomen showed thrombosis in the left renal vein and diffuse, heterogeneous enlargement of the left kidney. After nephrectomy, sulfur granules with chronic suppurative inflammation were seen microscopically, and the histopathological diagnosis was renal actinomycosis. Our case is the first report of renal actinomycosis with renal vein thrombosis.
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Actinomicose/complicações , Nefropatias/complicações , Veias Renais , Trombose Venosa/etiologia , Idoso , Humanos , Masculino , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: Women with systemic lupus erythematosus (SLE) are vulnerable to cervical dysplasia due to the persistence of human papillomavirus (HPV) infection. The objective of this cross-sectional retrospective study was to investigate the prevalence of cervical cancer screening according to the American Society for Colposcopy and Cervical Pathology (ASCCP) SLE-specific cervical cancer screening guidelines. We also aimed to identify SLE-specific determinants associated with ASCCP adherence. METHODS: Women aged 21 to 64 years enrolled in our institutional SLE registry were included in the study. The electronic medical record was manually reviewed to determine whether the patient was up to date on screening and which organizational guideline was used, in addition to other clinical variables. Multivariable logistic regression was used to estimate adjusted odds ratios (ORs) for ASCCP-congruent screening for each baseline characteristic. RESULTS: This study included 118 women with SLE; 38% were up to date per ASCCP guidelines, 16% were up to date per non-ASCCP guidelines, and 46% were overdue for screening. Having a gynecologist and being actively treated with immunosuppressant therapies were both associated with an increased odds of being up to date per the ASCCP guidelines, while Hispanic ethnicity was associated with reduced odds. CONCLUSION: Only half of the women with SLE in our study had guideline-congruent cervical cancer screening. Current immunosuppression exposure, rather than SLE disease activity, was associated with an increased odds of being up to date according to ASCCP guidelines. This study suggests the need for increased awareness and consensus among interdisciplinary providers regarding SLE-specific cervical cancer screening.
Assuntos
Lúpus Eritematoso Sistêmico , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/diagnóstico , Detecção Precoce de Câncer , Estudos Retrospectivos , Estudos Transversais , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Lúpus Eritematoso Sistêmico/complicaçõesRESUMO
BACKGROUND: To investigate the longitudinal relationship between physical frailty, the clinical representation of accelerated biological aging, and antidepressant medication response in older adults with depressive illness. METHODS: An 8-week randomized placebo-controlled trial (escitalopram or duloxetine) followed by 10 months of open antidepressant medication treatment (augmentation, switch strategies) was conducted in an outpatient research clinic. 121 adults aged 60 years or older with major depressive disorder (MDD) or persistent depressive disorder and a 24-item Hamilton Rating Scale for Depression (HRSD) ≥16 were enrolled. Primary measures assessed serially over 12 months include response (50% reduction from baseline HRSD score), remission (HRSD score <10), and frailty (non/intermediate frail [0-2 deficits] vs frail [≥3 deficits]); latent class analysis was used to classify longitudinal frailty trajectories. RESULTS: A 2-class model best fit the data, identifying a consistently low frailty risk (63% of the sample) and consistently high frailty risk (37% of the sample) trajectory. Response and remission rates (ps ≤ .002) for adults in the high-risk frailty class were at least 21 percentage points worse than those in the low-risk class over 12 months. Furthermore, subsequent frailty was associated with previous frailty (ps ≤ .01) but not previous response or remission (ps ≥ .10). CONCLUSIONS: Antidepressant medication is poorly effective for MDD occurring in the context of frailty in older adults. Furthermore, even when an antidepressant response is achieved, this response does little to improve their frailty. These data suggest that standard psychiatric assessment of depressed older adults should include frailty measures and that novel therapeutic strategies to address comorbid frailty and depression are needed.