RESUMO
BACKGROUND: Despite the increasing number of cases of secondary antibody deficiency (SAD) and immunoglobulin (Ig) utilization, there is a paucity of data in the literature on clinical and patient-reported outcomes in this population. OBJECTIVE: To describe immunoglobulin utilization patterns, clinical and patient-reported outcomes in patients with SAD on immunoglobulin replacement therapy (IgRT). METHODS: A cross-sectional study of patients with secondary antibody deficiency enrolled in the Ontario Immunoglobulin Treatment (ONIT) Case Registry from June 2020 to September 2022 was completed. Demographics, comorbidities, indications for immunoglobulin treatment, clinical infections at baseline and post IgRT, and patient-reported outcomes were collected and analyzed. RESULTS: There were 140 patients (58 males; 82 females; median age 68) with SAD during the study period; 131 were on subcutaneous Ig (SCIG) and 9 were on intravenous Ig (IVIG). The most common indication was chronic lymphocytic leukemia (CLL) (N = 52). IgRT reduced the average annual number of infections by 82.6%, emergency room (ER) visits by 84.6%, and hospitalizations by 83.3%. Overall, 84.6% of patients reported their health as better compared to before IgRT. Among those patients who switched from IVIG to SCIG (N = 35), 33.3% reported their health as the same, and 62.9% reported their health as better. CONCLUSIONS: This study demonstrates that IgRT significantly improved clinical outcomes and patient-reported general health state in patients with SAD. This study also further supports the use of SCIG in patients with SAD.
Assuntos
Imunoglobulinas Intravenosas , Síndromes de Imunodeficiência , Masculino , Feminino , Humanos , Idoso , Imunoglobulinas Intravenosas/uso terapêutico , Estudos Transversais , Ontário , Síndromes de Imunodeficiência/tratamento farmacológico , Imunoglobulina G , Sistema de RegistrosRESUMO
BACKGROUND: There is a paucity of studies reporting the presence of systemic symptoms and micronutrient deficiency in patients with chronic urticaria, and these data are lacking in a Canadian population. OBJECTIVE: To report the prevalence of gastrointestinal symptoms and vitamin B12 (cobalamin) deficiency in a Canadian patient population diagnosed with chronic urticaria. METHODS: A retrospective chart review of 100 adult patients with chronic urticaria was conducted. Demographic characteristics, medications, presence of gastrointestinal symptoms, and laboratory findings were abstracted from electronic medical records. RESULTS: Seventy percent of patients with chronic urticaria reported experiencing gastrointestinal symptoms. The most common symptom identified was gastroesophageal reflux (42%). Vitamin B12 (cobalamin) deficiency, defined as serum vitamin B12 level ≤ 250 pmol/L, was identified in 31.7% of the patients. Among those patients with urticaria and vitamin B12, 68% reported gastrointestinal symptoms. CONCLUSIONS: This is the first study to provide data on the high prevalence of gastrointestinal symptoms and vitamin B12 (cobalamin) deficiency in a Canadian population diagnosed with chronic urticaria. Early recognition and management of systemic symptoms and micronutrient deficiency may lead to a more comprehensive approach to management of these patients. Trial registration Not applicable.
RESUMO
Dupilumab is a novel anti-IL-4 receptor-α mAb that targets the signaling pathways of IL-4 and IL-13. Thus far, the data about adequate humoral immune response after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients who are taking dupilumab have been limited.
RESUMO
Several therapeutic strategies have been established to achieve maximal remission and improve quality of life in patients with chronic spontaneous urticaria. We previously reported dupilumab as a novel therapy for antihistamine-refractory chronic spontaneous urticaria patients who failed to respond to administration of omalizumab at increased doses for longer durations. This is the first case series to report data on the long-term duration of chronic spontaneous urticaria remission after discontinuation of dupilumab in patients who were able to obtain controlled chronic spontaneous urticaria. Six patients diagnosed with chronic spontaneous urticaria, who failed to respond to antihistamines and prolonged therapy with omalizumab at increased doses, were followed in this study for up to 34 months following initiation of dupilumab therapy. By demonstrating the maintenance of chronic spontaneous urticaria remission with dupilumab following discontinuation of therapy, in 67% of the patients, over an observation period up to 22 months, this case series highlights dupilumab's potential disease-modifying efficacy in patients affected by this disease.
RESUMO
The promise of blockchain has far-reaching ramifications for health-care stakeholders. Blockchain technology has the potential to improve health care by putting the patient at the centre of the system and improving health data security, privacy, and interoperability. This is a reflective piece to highlight the opportunities for applications of blockchain technology in the future of healthcare.
RESUMO
BACKGROUND: The Toronto protocol for cancer surveillance in children with Li-Fraumeni syndrome has been adopted worldwide. OBJECTIVE: To assess the diagnostic accuracy of the imaging used in this protocol. MATERIALS AND METHODS: We conducted a blinded retrospective review of imaging modalities in 31 pediatric patients. We compared imaging findings with the reference standards, which consisted of (1) histopathological diagnosis, (2) corresponding dedicated imaging or subsequent surveillance imaging or (3) clinical outcomes. We individually analyzed each modality's diagnostic performance for cancer detection and assessed it on a per-study basis for chest and abdominal regional whole-body MRI (n=115 each), brain MRI (n=101) and abdominal/pelvic US (n=292), and on a per-lesion basis for skeleton/soft tissues on whole-body MRI (n=140). RESULTS: Of 763 studies/lesions, approximately 80% had reference standards that identified 4 (0.7%) true-positive, 523 (85.3%) true-negative, 5 (0.8%) false-positive, 3 (0.5%) false-negative and 78 (12.7%) indeterminate results. There were 3 true-positives on whole-body MRI and 1 true-positive on brain MRI as well as 3 false-negatives on whole-body MRI. Sensitivities and specificities of tumor diagnosis using a worst-case scenario analysis were, respectively, 40.0% (95% confidence interval [CI]: 7.3%, 83.0%) and 38.2% (95% CI: 29.2%, 48.0%) for skeleton/soft tissues on whole-body MRI; sensitivity non-available and 97.8% (95% CI: 91.4%, 99.6%) for chest regional whole-body MRI; 100.0% (95% CI: 5.5%, 100.0%) and 96.8% (95% CI: 90.2%, 99.2%) for abdominal regional whole-body MRI; sensitivity non-available and 98.3% (95% CI: 95.3, 99.4) for abdominal/pelvic US; and 50.0% (95% CI: 2.7%, 97.3%) and 93.8% (95% CI: 85.6%, 97.7%) for brain MRI. CONCLUSION: Considerations for optimizing imaging protocol, defining criteria for abnormalities, developing a structured reporting system, and practicing consensus double-reading may enhance the diagnostic accuracy for tumor surveillance.
Assuntos
Síndrome de Li-Fraumeni , Criança , Detecção Precoce de Câncer/métodos , Humanos , Síndrome de Li-Fraumeni/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Compostos Radiofarmacêuticos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To assess the prevalence of visual impairment and unmet eye care needs of the Syrian adult refugee population in Canada. DESIGN: Cross-sectional descriptive study. PARTICIPANTS: Enrolment was offered to all Syrian refugees 18 years or older, with 248 patients enrolled. METHODS: Five clinics were organized from July 2016 to November 2017 in Toronto, Ontario. A vision screening and dilated retinal examination was performed on all participants. Prevalence of visual impairment and nonrefractive pathologies as well as information on sociodemographics and subjective visual acuity were obtained. RESULTS: The mean age of participants was 36 years (interquartile range, 30-35) and 53% were females. The prevalence of reported uncorrected vision problems was 22.2% for distance vision, 6.5% for near vision, and 5.6% for both distance and near vision, including loss of vision. Compared with the Canadian population, Syrian adult refugees were 19.04 times more likely to report uncorrected vision problems (34.4% vs 1.8%, p < 0.01). The presenting visual acuity in the better-seeing eye was 20/50 or worse in 19.4%. Pinhole improved this to 12.5% (95% confidence interval [CI], 8.7%-17.3%). Compared with the Canadian population (0.95%), Syrian adult refugees were 13 times more likely to have 20/50 vision or worse (p < 0.01). The most common finding was refractive error in 46.0% (95% CI, 39.6%-52.4%) followed by nonrefractive error in 30.2% (95% CI, 24.9%-36.2%). CONCLUSIONS: This is the first study to assess ocular health in a refugee population in Canada. Syrian adult refugees have a high prevalence of visual impairment, even when living within a system of universal health care.
Assuntos
Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Refugiados/estatística & dados numéricos , Transtornos da Visão/epidemiologia , Pessoas com Deficiência Visual/estatística & dados numéricos , Adolescente , Adulto , Estudos Transversais , Feminino , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Inquéritos e Questionários , Síria/etnologia , Seleção Visual , Acuidade Visual/fisiologia , Adulto JovemRESUMO
OBJECTIVE: To assess the ocular health status of Syrian pediatric refugees in Canada and report the prevalence of vision impairment within this population. DESIGN: Cross-sectional descriptive study. PARTICIPANTS: Syrian refugees 18 years old or younger. METHODS: Five clinic days were organized from July 2016 to November 2017 in Toronto, Ontario. A total of 274 patients were enrolled. Data collection involved surveys, vision screening, and ocular examinations. χ2 was used for statistical analysis. RESULTS: The prevalence of uncorrected vision was 17.2% for distance, 4.7% for near, and 0.7% for both distance and near vision, including loss of vision. Of these, 95.3% had not visited an eye specialist in the past year, and 25.2% of parents were dissatisfied with their children's vision. The presenting visual acuity in the better-seeing eye was 20/50 or worse in 5.8% (95% confidence interval [CI] 3.6%-9.3%), and this did not correct with pinhole. This rate is 32 times (p < 0.01) higher than the prevalence rate in the average Canadian pediatric population (0.17%). Uncorrected refractive error prevalence was 26.3% (95% CI 21.2%-31.9%), with the most common etiology being myopia (19.7% CI 15.2%-24.9%). Myopia was 17.9 times (p < 0.0001) more prevalent among our Syrian refugee children compared with the average Canadian pediatric population (1.1%). CONCLUSION: Syrian pediatric refugees residing in Canada have a high prevalence of vision problems. Comprehensive vision screening, improved access to eye clinics, and developing evidence-based guidelines may help address the unmet eye care needs of this vulnerable population.
Assuntos
Serviços de Saúde da Criança/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Refugiados/estatística & dados numéricos , Transtornos da Visão/epidemiologia , Pessoas com Deficiência Visual/estatística & dados numéricos , Canadá/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Miopia/epidemiologia , Prevalência , Inquéritos e Questionários , Síria/etnologia , Seleção Visual , Acuidade VisualRESUMO
Aims: Transforming growth factor ß1 (TGF-ß1) is a prosclerotic cytokine involved in cardiac remodelling leading to heart failure (HF). Acetylation/de-acetylation of specific lysine residues in Smad2/3 has been shown to regulate TGF-ß signalling by altering its transcriptional activity. Recently, the lysine de-acetylase sirtuin 1 (SIRT1) has been shown to have a cardioprotective effect; however, SIRT1 expression and activity are paradoxically reduced in HF. Herein, we investigate whether pharmacological activation of SIRT1 would induce cardioprotection in a pressure overload model and assess the impact of SIRT1 activation on TGF-ß signalling and the fibrotic response. Methods and results: Eight weeks old male C57BL/6 mice were randomized to undergo sham surgery or transverse aortic constriction (TAC) to induce pressure overload. Post-surgery, animals were further randomized to receive SRT1720 or vehicle treatment. Echocardiography, pressure-volume loops, and histological analysis revealed an impairment in cardiac function and deleterious left ventricular remodelling in TAC-operated animals that was improved with SRT1720 treatment. Genetic ablation and cell culture studies using a Smad-binding response element revealed SIRT1 to be a specific target of SRT1720 and identified Smad2/3 as a SIRT1 specific substrate. Conclusion: Overall, our data demonstrate that Smad2/3 is a specific SIRT1 target and suggests that pharmacological activation of SIRT1 may be a novel therapeutic strategy to prevent/reverse HF via modifying Smad activity.
Assuntos
Ativadores de Enzimas/farmacologia , Insuficiência Cardíaca/prevenção & controle , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Hipertrofia Ventricular Esquerda/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Sirtuína 1/metabolismo , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Acetilação , Animais , Células Cultivadas , Modelos Animais de Doenças , Ativação Enzimática , Fibrose , Insuficiência Cardíaca/enzimologia , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/fisiopatologia , Histonas/metabolismo , Humanos , Hipertrofia Ventricular Esquerda/enzimologia , Hipertrofia Ventricular Esquerda/genética , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/patologia , Fosforilação , Processamento de Proteína Pós-Traducional , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/genética , Fator de Crescimento Transformador beta/metabolismoRESUMO
The capacity of stem and progenitor cells to stimulate cardiac regeneration has been studied for almost 20 years, with very promising preclinical data and mixed clinical results. Several cell types have been studied, identified by their cell surface markers, differentiation capacity and their secreted growth factors. Bone marrow derived mesenchymal stem cells (MSCs) have been found to have potent regenerative capacity, through multiple mechanisms, including mesoderm lineage differentiation, immunomodulation, and paracrine stimulation. MSCs also secrete exosomes and microvesicles, which themselves contain potent angiogenic cytokines or mRNA molecules with effects on their local milieu. This concise review summarizes the mechanisms of MSC-based cardiac regeneration and highlighting results from molecular and preclinical studies. We also discuss clinical trial results to date, and ongoing studies. Furthermore, we discuss novel approaches for the enhancement of MSC based cardiac regeneration, such as genetic modification. Stem Cells Translational Medicine 2018;7:543-550.
Assuntos
Transplante de Células-Tronco Mesenquimais , Isquemia Miocárdica/terapia , Animais , Diferenciação Celular , Ensaios Clínicos como Assunto , Exossomos/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Comunicação ParácrinaRESUMO
Cardiac fibrosis is a common finding in patients with chronic kidney disease. Here, we investigate the cardio-renal effects of theracurmin, a novel formulation of the polyphenolic compound curcumin, in a rat model of chronic kidney disease. Briefly, Sprague-Dawley rats were randomized to undergo sham or subtotal nephrectomy (SNx) surgery. At 3 weeks post surgery, SNx animals were further randomized to received theracurmin via once daily oral gavage or vehicle for 5 consecutive weeks. At 8 weeks post surgery, cardiac function was assessed via echocardiography and pressure volume loop analysis, followed by LV and renal tissue collection for analysis. SNx animals developed key hallmarks of renal injury including hypertension, proteinuria, elevated blood urea nitrogen, and glomerulosclerosis. Renal injury in SNx animals was also associated with significant diastolic dysfunction, macrophage infiltration, and cardiac NLRP3 inflammasome activation. Treatment of SNx animals with theracurmin improved structural and functional manifestations of cardiac injury associated with renal failure and also attenuated cardiac NLRP3 inflammasome activation and mature IL-1ß release. Taken together, our findings suggest a significant role for the NLRP3 inflammasome in renal injury-induced cardiac dysfunction and presents inflammasome attenuation as a unique strategy to prevent adverse cardiac remodeling in the setting of chronic kidney disease.
Assuntos
Fibrose/patologia , Inflamassomos/metabolismo , Miocárdio/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Insuficiência Renal Crônica/complicações , Animais , Pressão Sanguínea , Peso Corporal , Diástole , Ecocardiografia , Interleucina-1beta/metabolismo , Falência Renal Crônica , Macrófagos/citologia , Masculino , Nefrectomia , Polifenóis/química , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: In addition to degrading glucagon-like peptide-1 (GLP-1), dipeptidyl peptidase-4 (DPP-4) inactivates several chemokines, including stromal cell-derived factor-1α (SDF-1α), a pro-angiogenic and cardiomyocyte protective protein. We hypothesized that DPP-4 inhibition may confer benefit following myocardial infarction (MI) in the diabetic setting as a consequence of enhanced SDF-1α availability rather than potentiating GLP-1. To test this we compared the effects of saxagliptin with those of liraglutide and used the SDF-1α receptor (CXCR4) antagonist plerixafor. METHODS: Studies were conducted in streptozotocin-diabetic rats. Rats were randomized to receive saxagliptin (10 mg/kg per day), liraglutide (0.2 mg/kg, s.c., b.i.d.), plerixafor (1 mg/kg per day, s.c.), saxagliptin plus plerixafor or vehicle (1% phosphate-buffered saline). Two weeks later, rats underwent experimental MI, with cardiac function examined 4 weeks after MI. RESULTS: Glycemic control and MI size were similar in all groups. Four weeks after MI, mortality was reduced in saxagliptin-treated rats compared with vehicle treatment (P < 0.05). Furthermore, rats receiving saxagliptin had improved cardiac function compared with vehicle-treated rats (P < 0.05). Antagonism of CXCR4 prevented the improvement in cardiac function in saxagliptin-treated rats and was associated with increased mortality (P < 0.05). CONCLUSION: Saxagliptin-mediated DPP-4 inhibition, but not liraglutide-mediated GLP-1R agonism, improved cardiac function after MI independent of glucose lowering. These findings suggest that non-GLP-1 actions of DPP-4 inhibition, such as SDF-1α potentiation, mediate biological effects.
Assuntos
Adamantano/análogos & derivados , Quimiocina CXCL12/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Dipeptídeos/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Infarto do Miocárdio/fisiopatologia , Adamantano/uso terapêutico , Animais , Benzilaminas , Cateterismo Cardíaco , Ciclamos , Diabetes Mellitus Experimental/tratamento farmacológico , Dipeptidil Peptidase 4/metabolismo , Ecocardiografia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Compostos Heterocíclicos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Liraglutida/uso terapêutico , Masculino , Infarto do Miocárdio/metabolismo , Ratos , Ratos Endogâmicos F344RESUMO
Mechanisms for visuospatial cognition are often inferred directly from errors in behavioral reports of remembered target direction. For example, gaze-centered target representations for reach were first inferred from reach overshoots of target location relative to gaze. Here, we report evidence for the hypothesis that these gaze-dependent reach errors stem predominantly from misestimates of hand rather than target position, as was assumed in all previous studies. Subjects showed typical gaze-dependent overshoots in complete darkness, but these errors were entirely suppressed by continuous visual feedback of the finger. This manipulation could not affect target representations, so the suppressed gaze-dependent errors must have come from misestimates of hand position, likely arising in a gaze-dependent transformation of hand position signals into visual coordinates. This finding has broad implications for any task involving localization of visual targets relative to unseen limbs, in both healthy individuals and patient populations, and shows that response-related transformations cannot be ignored when deducing the sources of gaze-related errors.