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1.
Pediatrics ; 148(5)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34716218

RESUMO

OBJECTIVES: We aimed to reassess the relationship between phototherapy and cancer in an extended version of a previous cohort and to replicate a report from Quebec of increased cancer risk after phototherapy beginning at age 4 years. METHODS: This cohort study included 139 100 children born at ≥35 weeks' gestation from 1995 to 2017, followed through March 16, 2019, in Kaiser Permanente Northern California hospitals who had a qualifying bilirubin level from -3 mg/dL to +4.9 mg/dL from the American Academy of Pediatrics phototherapy threshold; an additional 40 780 children and 5 years of follow-up from our previous report. The exposure was inpatient phototherapy (yes or no), and the outcomes were various types of childhood cancer. We used Cox proportional hazard models, controlling for propensity-score quintiles, and allowed for time-dependent exposure effects to assess for the risk of cancer after a latent period. RESULTS: Over a mean (SD) follow-up of 8.2 (5.7) years, the crude incidence of cancer per 100 000 person-years was 25.1 among those exposed to phototherapy and 19.2 among those not exposed (233 cases of cancer). After propensity adjustment, phototherapy was not associated with any cancer (hazard ratio [HR]: 1.13, 95% confidence interval [CI]: 0.83-1.54), hematopoietic cancer (HR: 1.17, 95% CI: 0.74-1.83), or solid tumors (HR: 1.01, 95% CI: 0.65-1.58). We also found no association with cancer diagnoses at age ≥4 years. CONCLUSIONS: We did not confirm previous, concerning associations between phototherapy and adjusted risk of any cancer, nonlymphocytic leukemia, or brain and/or central nervous systems tumors in later childhood.


Assuntos
Neoplasias/etiologia , Fototerapia/efeitos adversos , Bilirrubina/sangue , California/epidemiologia , Criança , Pré-Escolar , Métodos Epidemiológicos , Feminino , Humanos , Incidência , Masculino , Resultados Negativos , Neoplasias/epidemiologia , Fatores de Tempo
2.
Isr Med Assoc J ; 23(10): 635-638, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34672445

RESUMO

BACKGROUND: Venous thromboembolism (VTE) is a serious disease, which demands a fast accurate diagnosis to begin suitable treatment. It presents a major problem in the emergency department (ED), and its confirmation requires adequate evaluation. OBJECTIVES: To evaluate a potential role of mean platelet volume (MPV) in differentiating VTE from other potential diagnosis in patients with suspected VTE. METHODS: We conducted a retrospective case-controlled study of 440 consecutive patients who presented to the ED of our hospital with clinical VTE, but only 316 with proven VTE. A control group was composed of patients (124) who presented with clinical VTE but without proven VTE. We checked the MPV value in all 440 patients and the correlation with VTE occurrence in the study group vs. control group. RESULTS: Statistical analysis of the acquired results indicated that MPV value could not aid in determining the difference of real VTE vs. patients with VTE-like clinical picture presenting to the ED. We found an inverse correlation between MPV value and proven VTE, in contrast to most researchers who have studied the same issue. CONCLUSIONS: Although MPV can be a useful diagnostic marker in many diseases, we found no definite association between low MPV and VTE.


Assuntos
Diagnóstico Precoce , Volume Plaquetário Médio/métodos , Tromboembolia Venosa , Estudos de Casos e Controles , Diagnóstico Diferencial , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Resultados Negativos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tempo para o Tratamento , Tromboembolia Venosa/sangue , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologia
3.
Isr Med Assoc J ; 23(10): 646-650, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34672447

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory and destructive joint disease with the presence of autoantibodies, rheumatoid factor (RF), and anti-citrullinated protein antibodies (ACPA). The presence of RF or ACPA predicts RA severity. Data on the influence of ACPA titer on RA course are limited. OBJECTIVES: To determine the correlation between ACPA titers at the time of RA diagnosis to RA features and severity during 3 years of follow-up. METHODS: We performed a retrospective study of RA patients treated at our institution during the years 2006-2015 with known ACPA titers at RA diagnosis who completed at least 3 years of follow-up. Patients (N=133) were divided according to ACPA titer: seronegative (< 15 U/ml, n=55), weakly positive (15-49 U/ml, n=18), moderately positive (50-300 U/ml, n=29), and strongly positive (> 300 U/ml, n=31). Patient data, including disease activity score (DAS28), bone erosion on hand and/or foot X-rays, treatments with corticosteroids and disease-modifying-anti-rheumatic drugs (DMARDs), and hospitalizations, were recorded. Chi-square and Mann-Whitney method were used for statistical analysis. P < 0.05 was considered as statistically significant. RESULTS: Male gender, smoking, and RF positivity correlated with ACPA positivity and higher ACPA titers. There was no correlation between ACPA titer and the variables defined as representing RA severity: higher DAS28, bone erosions, hospitalizations, need for corticosteroids, and conventional and biological DMARDs. CONCLUSIONS: Titer of ACPA was not identified as a predictive factor for RA severity.


Assuntos
Corticosteroides/uso terapêutico , Anticorpos Anti-Proteína Citrulinada/sangue , Antirreumáticos/uso terapêutico , Artrite Reumatoide , Monitorização Imunológica , Radiografia , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/imunologia , Correlação de Dados , Progressão da Doença , Feminino , Humanos , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Monitorização Imunológica/métodos , Monitorização Imunológica/estatística & dados numéricos , Resultados Negativos , Gravidade do Paciente , Valor Preditivo dos Testes , Prognóstico , Radiografia/métodos , Radiografia/estatística & dados numéricos , Estudos Retrospectivos , Fator Reumatoide/sangue , Índice de Gravidade de Doença
5.
BMC Pregnancy Childbirth ; 21(1): 617, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496798

RESUMO

BACKGROUND: Acute fatty liver of pregnancy (AFLP) is an acute, rare and potentially lethal disease typically occurring in the third trimester of pregnancy. So far, there is no effective means of prevention. Therefore, in this study, we retrospectively analyzed the clinical features of AFLP patients for a better understanding. Meanwhile, for the first time, the genetic background associated with the onset of AFLP was discussed by high-throughput sequencing, hoping to provide evidence for genetic counseling and prenatal diagnosis of AFLP. METHODS: Thirteen AFLP patients admitted to our hospital and other hospital from March 2012 to February 2020 were selected. Clinical data about general condition, laboratory test, liver biopsy and the prognosis of mother and fetus were collected for retrospective analysis. In addition, the peripheral blood of five patients with AFLP and one newborn infant of his mother with AFLP was sequenced with whole-exome sequencing and gene mutation was analyzed by bioinformatics methods. RESULTS: The initial symptoms of AFLP varied differently, with jaundice (9/13, 69%), fatigue (8/13, 62%) and nausea and vomiting (6/13, 46%) being the most common. Moreover, the main maternal complications were coagulopathy (13/13, 100%), followed by acute renal dysfunction (10/13, 77%). Raised serum bilirubin, transaminases and uric acid were found in all patients (100%), hypoglycemia was found in six patients (46%) and fatty liver on ultrasound was seen in five patients (5/12, 42%). One (7%) maternal death occurred and all neonates survived delivery. In addition, to our surprise, whole-exome sequencing showed that no gene mutation in related enzymes involved in fatty acid metabolism was noted in the pregnant women and children receiving genetic testing. CONCLUSIONS: Early visit, early detection, early termination of pregnancy and multidisciplinary comprehensive treatment are the key factors to improve the prognosis of AFLP patients and their newborn infants. Furthermore, although limited size of study, to our knowledge, this report is the first to present the lack of common mutation involved in fatty acid oxidation in Chinese patients with AFLP via whole-exome sequencing. Thus, further studies are needed with larger and more varied samples to validate the conclusion.


Assuntos
Fígado Gorduroso/genética , Fígado Gorduroso/patologia , Testes Genéticos , Complicações na Gravidez/genética , Complicações na Gravidez/patologia , Sequenciamento Completo do Exoma , Adulto , China/epidemiologia , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/terapia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Recém-Nascido , Resultados Negativos , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/terapia , Estudos Retrospectivos , Análise de Sequência de DNA/métodos
6.
Sci Rep ; 11(1): 16270, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381142

RESUMO

mTOR inhibitors offer advantages after kidney transplantation including antiviral and antitumor activity besides facilitating low calcineurin inhibitor exposure to reduce nephrotoxicity. Concerns about adverse effects due to antiproliferative and antiangiogenic properties have limited their clinical use particularly early after transplantation. Interference with vascular endothelial growth factor (VEGF)-A, important for physiologic functioning of renal endothelial cells and tubular epithelium, has been implicated in detrimental renal effects of mTOR inhibitors. Low doses of Rapamycin (loading dose 3 mg/kg bodyweight, daily doses 1.5 mg/kg bodyweight) were administered in an allogenic rat kidney transplantation model resulting in a mean through concentration of 4.30 ng/mL. Glomerular and peritubular capillaries, tubular cell proliferation, or functional recovery from preservation/reperfusion injury were not compromised in comparison to vehicle treated animals. VEGF-A, VEGF receptor 2, and the co-receptor Neuropilin-1 were upregulated by Rapamycin within 7 days. Rat proximal tubular cells (RPTC) responded in vitro to hypoxia with increased VEGF-A and VEGF-R1 expression that was not suppressed by Rapamycin at therapeutic concentrations. Rapamycin did not impair proliferation of RPTC under hypoxic conditions. Low-dose Rapamycin early posttransplant does not negatively influence the VEGF network crucial for recovery from preservation/reperfusion injury. Enhancement of VEGF signaling peritransplant holds potential to further improve outcomes.


Assuntos
Transplante de Rim , Túbulos Renais Proximais/irrigação sanguínea , Túbulos Renais Proximais/fisiologia , Resultados Negativos , Regeneração/efeitos dos fármacos , Sirolimo/efeitos adversos , Animais , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Expressão Gênica/efeitos dos fármacos , Túbulos Renais Proximais/citologia , Masculino , Ratos Endogâmicos F344 , Ratos Endogâmicos Lew , Traumatismo por Reperfusão/genética , Sirolimo/administração & dosagem , Sirolimo/farmacologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/fisiologia
7.
J Clin Neurosci ; 90: 325-331, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34275571

RESUMO

BACKGROUND: Idiopathic Normal Pressure Hydrocephalus (iNPH) can be effectively treated through shunt insertion. However, most shunted patients experience little or no clinical benefit, which suggests suboptimal patient selection. While contentious, multiple studies have reported poorer shunt outcomes associated with concomitant Alzheimer's disease. Prompted by this observation, multiple studies have assessed the role of amyloid PET, a specific test for Alzheimer's disease, in patient selection for shunting. METHODS: A comprehensive literature search was performed to identify studies that assessed the association between amyloid PET result and the clinical response to shunting in patients with suspected iNPH. Pooled diagnostic statistics were calculated. RESULTS: Across three relevant studies, a total of 38 patients with suspected iNPH underwent amyloid PET imaging and shunt insertion. Twenty-three patients had a positive clinical response to shunting. 18/28 (64.3%) of patients with a negative amyloid PET and 5/10 (50%) with a positive amyloid PET had a positive response to shunting. The pooled sensitivity, specificity and accuracy was 33.3%, 76.2% and 58.3%. None of these statistics reached statistical significance. CONCLUSION: The results of this pooled analysis do not support the selection of patients with suspected iNPH for shunting on the basis of amyloid PET alone. However, due to small cohort sizes and weakness in study design, further high-quality studies are required to properly determine the role of amyloid PET in assessing this complex patient group.


Assuntos
Amiloide , Derivações do Líquido Cefalorraquidiano/métodos , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Hidrocefalia de Pressão Normal/cirurgia , Tomografia por Emissão de Pósitrons/métodos , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultados Negativos , Seleção de Pacientes , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento
8.
Sci Rep ; 11(1): 14836, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34290340

RESUMO

While human papillomavirus is the primary cause of cervical cancer, other factors may influence susceptibility and response to the virus. Candidates include douching and talcum powder applied in the genital area. We used Cox proportional hazards models to estimate confounder-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) in the Sister Study (2003-2009), a US cohort of women aged 35-74. We considered pre-baseline (n = 523) and incident (n = 31) cervical cancers. Douching at ages 10-13 was positively associated with pre-baseline cervical cancer (HR 1.32, 95% CI 0.86-2.03), though the association was not statistically significant. We did not observe an association between adolescent talc use and pre-baseline cervical cancer (HR 0.95, 95% CI 0.76-1.19). Douching in the year before enrollment was positively associated with incident cervical cancer (HR 2.56, 95% CI 1.10-5.99). The association between recent genital talc use and incident cervical cancer was positive, but not statistically significant (HR 1.79, 95% CI 0.78-4.11). The observed positive association between douching and incident cervical cancer is consistent with previous retrospective case-control studies. In the first study to examine genital talc use and cervical cancer, we did not see evidence of an association.


Assuntos
Talco/efeitos adversos , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/etiologia , Ducha Vaginal/efeitos adversos , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Resultados Negativos , Papillomaviridae/patogenicidade , Prevalência , Risco
9.
J Am Heart Assoc ; 10(15): e020418, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34278803

RESUMO

Background Sodium-glucose cotransporter 2 inhibitors reduce hospitalizations for heart failure and cardiovascular death, although the underlying mechanisms have not been resolved. The SIMPLE trial (The Effects of Empagliflozin on Myocardial Flow Reserve in Patients With Type 2 Diabetes Mellitus) investigated the effects of empagliflozin on myocardial flow reserve (MFR) reflecting microvascular perfusion, in patients with type 2 diabetes mellitus at high cardiovascular disease risk. Methods and Results We randomized 90 patients to either empagliflozin 25 mg once daily or placebo for 13 weeks, as add-on to standard therapy. The primary outcome was change in MFR at week 13, quantified by Rubidium-82 positron emission tomography/computed tomography. The secondary key outcomes were changes in resting rate-pressure product adjusted MFR, changes to myocardial flow during rest and stress, and reversible cardiac ischemia. Mean baseline MFR was 2.21 (95% CI, 2.08-2.35). There was no change from baseline in MFR at week 13 in either the empagliflozin: 0.01 (95% CI, -0.18 to 0.21) or placebo groups: 0.06 (95% CI, -0.15 to 0.27), with no treatment effect -0.05 (95% CI, -0.33 to 0.23). No effects on the secondary outcome parameters by Rubidium-82 positron emission tomography/computed tomography was observed. Treatment with empagliflozin reduced hemoglobin A1c by 0.76% (95% CI, 1.0-0.5; P<0.001) and increased hematocrit by 1.69% (95% CI, 0.7-2.6; P<0.001). Conclusions Empagliflozin did not improve MFR among patients with type 2 diabetes mellitus and high cardiovascular disease risk. The present study does not support that short-term improvement in MFR explains the reduction in cardiovascular events observed in the outcome trials. Registration URL: https://clinicaltrialsregister.eu/; Unique identifier: 2016-003743-10.


Assuntos
Compostos Benzidrílicos , Diabetes Mellitus Tipo 2 , Reserva Fracionada de Fluxo Miocárdico/efeitos dos fármacos , Glucosídeos , Hemoglobina A Glicada/análise , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/farmacocinética , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Glucosídeos/administração & dosagem , Glucosídeos/farmacocinética , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Microcirculação/efeitos dos fármacos , Pessoa de Meia-Idade , Imagem de Perfusão do Miocárdio/métodos , Resultados Negativos , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/farmacocinética
10.
Endocrine ; 74(1): 155-162, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34272648

RESUMO

PURPOSE: Few studies have assessed the clinical features of pheochromocytoma and paraganglioma (PPGL) not producing excessive catecholamine. We aimed to clarify the clinical characteristics of PPGL patients with negative results for urinary metanephrines. METHODS: This is a retrospective cross-sectional study. We established a database by combining datasets from the Nationwide Cohort Study on the Development of Diagnosis and Treatment of Pheochromocytoma in Japan (PHEO-J) and the Advancing Care and Pathogenesis of Intractable Adrenal diseases in Japan (ACPA-J). We compared the clinical differences between PPGL patients with negative results for urinary metanephrines and those with catecholamine-producing PPGL. RESULTS: Five hundred PPGL patients in the combined database were analyzed. Among them, 31 were negative for metanephrines. PPGL with negative results for urinary metanephrines was significantly associated with extra-adrenal disease (Odds ratio (OR) 6.58, 95% CI (confidence interval) 3.03-14.3, p < 0.001), the presence of metastatic disease (OR 4.22, 95% CI 1.58-11.3, p = 0.004), and negativity on meta-iodobenzylguanidine (MIBG) scintigraphy (OR 0.15, 95% CI 0.03-0.77, p = 0.023). CONCLUSIONS: Our findings demonstrate that PPGL patients with negative results for urinary metanephrines are associated with extra-adrenal lesions, metastatic disease, and negative MIBG findings. This suggests that PPGL patients with negative results for urinary metanephrines have a greater need for systemic whole-body imaging other than MIBG scintigraphy and close follow-up to monitor for metastasis than do patients with PPGL overtly producing excessive catecholamine.


Assuntos
Neoplasias das Glândulas Suprarrenais , Paraganglioma , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Estudos de Coortes , Estudos Transversais , Humanos , Metanefrina , Resultados Negativos , Paraganglioma/diagnóstico por imagem , Estudos Retrospectivos
11.
Cochrane Database Syst Rev ; 6: CD012923, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34085713

RESUMO

BACKGROUND: Thoracic aortic arch aneurysms (TAAs) can be a life-threatening condition due to the potential risk of rupture. Treatment is recommended when the risk of rupture is greater than the risk of surgical complications. Depending on the cause, size and growth rate of the TAA, treatment may vary from close observation to emergency surgery. Aneurysms of the thoracic aorta can be managed by a number of surgical techniques. Open surgical repair (OSR) of aneurysms involves either partial or total replacement of the aorta, which is dependent on the extent of the diseased segment of the aorta. During OSR, the aneurysm is replaced with a synthetic graft. Hybrid repair (HR) involves a combination of open surgery with endovascular aortic stent graft placement. Hybrid repair requires varying degrees of invasiveness, depending on the number of supra-aortic branches that require debranching. The hybrid technique that combines supra-aortic vascular debranching with stent grafting of the aortic arch has been introduced as a therapeutic alternative. However, the short- and long-term outcomes of HR remain unclear, due to technical difficulties and complications as a result of the angulation of the aortic arch as well as handling of the arch during surgery. OBJECTIVES: To assess the effectiveness and safety of HR versus conventional OSR for the treatment of TAAs. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and AMED databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 22 March 2021. We also searched references of relevant articles retrieved from the electronic search for additional citations. SELECTION CRITERIA: We considered for inclusion in the review all published and unpublished randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing HR to OSR for TAAs. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all titles and abstracts obtained from the literature search to identify those that met the inclusion criteria. We retrieved the full text of studies deemed as potentially relevant by at least one review author. The same review authors screened the full-text articles independently for inclusion or exclusion. MAIN RESULTS: No RCTs or CCTs met the inclusion criteria for this review. AUTHORS' CONCLUSIONS: Due to the lack of RCTs or CCTs, we were unable to determine the safety and effectiveness of HR compared to OSR in people with TAAs, and we are unable to provide high-certainty evidence on the optimal surgical intervention for this cohort of patients. High-quality RCTs or CCTs are necessary, addressing the objective of this review.


Assuntos
Aneurisma da Aorta Torácica/cirurgia , Resultados Negativos , Humanos
12.
J Med Virol ; 93(10): 5947-5952, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34170561

RESUMO

Coronavirus disease 2019 (COVID-19) is an infectious disease, and the reason behind the currently ongoing pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme (ACE2) has been recognized as the specific receptor of the SARS-CoV-2 virus. Although the possible effect of ACE2 gene polymorphism remains unknown, human ACE2 receptor expression influences SARS-CoV-2 susceptibility and COVID-19 disease outcome. In this study, we aimed to investigate the relationship between ACE gene I/D polymorphism, ACE2 receptor gene polymorphism, and COVID-19 severity. ACE gene insertion/deletion (I/D) polymorphism and ACE2 receptor gene rs2106809 and rs2285666 polymorphisms were determined using polymerase chain reaction (PCR) and PCR-based restriction fragment length polymorphism methods, respectively, in 155 COVID-19 patients who were divided into three groups (mild, moderate, and severe) according to clinical symptoms. However, the distribution of genotype and allele frequencies of ACE gene I/D, ACE2 receptor gene rs2106809, and rs2285666 polymorphisms were not statistically significant in all groups. In conclusion, in the study population, ACE gene I/D, ACE2 receptor gene rs2106809, and rs2285666 polymorphisms were not associated with the severity of COVID-19 infection. Although ACE2 receptor gene expression may affect the susceptibility to COVID-19, there is no existing evidence that the ACE or ACE2 gene polymorphisms are directly associated with COVID-19 severity. Interindividual differences in COVID-19 severity might be related to epigenetic mechanisms of ACE2 receptor gene expression or variations in other genes suggested to play a critical role in COVID-19 pathogenesis such as pro-inflammatory cytokines and coagulation indicators.


Assuntos
Enzima de Conversão de Angiotensina 2/genética , COVID-19/genética , Peptidil Dipeptidase A/genética , Adulto , Idoso , COVID-19/diagnóstico , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Pessoa de Meia-Idade , Resultados Negativos , Polimorfismo de Nucleotídeo Único , SARS-CoV-2 , Índice de Gravidade de Doença
13.
Am Heart J ; 241: 6-13, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34118202

RESUMO

BACKGROUND: Kidney function may promote progression of AF. OBJECTIVE: We evaluated the association of kidney function to AF progression and resultant clinical outcomes in patients with cardiac implantable electronic devices (CIED). METHODS: We performed a retrospective cohort study using national clinical data from the Veterans Health Administration linked to CIED data from the Carelink® remote monitoring data warehouse (Medtronic Inc, Mounds View, MN). All devices had atrial leads and at least 75% of remote monitoring transmission coverage. Patients were included at the date of the first AF episode lasting ≥6 minutes, and followed until the occurrence of persistent AF in the first year, defined as ≥7 consecutive days with continuous AF. We used Cox regression analyses with persistent AF as a time-varying covariate to examine the association to stroke, myocardial infarction, heart failure and death. RESULTS: Of, 10,323 eligible patients, 1,771 had a first CIED-detected AF (mean age 69 ± 10 years, 1.2% female). In the first year 355 (20%) developed persistent AF. Kidney function was not associated with persistent AF after multivariable adjustment including CHA2DS2-VASc variables and prior medications. Only higher age increased the risk (HR: 1.37 per 10 years; 95% CI:1.22-1.54). Persistent AF was associated to higher risk of heart failure (HR: 2.27; 95% CI: 1.88-2.74) and death (HR: 1.60; 95% CI: 1.30-1.96), but not stroke (HR: 1.28; 95% CI: 0.62-2.62) or myocardial infarction (HR: 1.43; 95% CI: 0.91-2.25). CONCLUSION: Kidney function was not associated to AF progression, whereas higher age was. Preventing AF progression could reduce the risk of heart failure and death.


Assuntos
Fibrilação Atrial , Insuficiência Cardíaca , Testes de Função Renal , Monitorização Fisiológica , Acidente Vascular Cerebral , Fatores Etários , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/mortalidade , Fibrilação Atrial/fisiopatologia , Correlação de Dados , Eletrodos Implantados/estatística & dados numéricos , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Humanos , Testes de Função Renal/métodos , Testes de Função Renal/estatística & dados numéricos , Masculino , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Monitorização Fisiológica/estatística & dados numéricos , Resultados Negativos , Tecnologia de Sensoriamento Remoto/instrumentação , Tecnologia de Sensoriamento Remoto/estatística & dados numéricos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Estados Unidos/epidemiologia , Saúde dos Veteranos/estatística & dados numéricos
14.
Respir Med ; 184: 106466, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34010739

RESUMO

Alpha1-antitrypsin deficiency arises due to mutations in alpha1-antitrypsin (AAT) gene and represents the most prominent genetic predisposition to chronic obstructive pulmonary disease and emphysema. Since AAT plays important immunomodulatory and tissue-protective roles and since it was suggested to protect from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we assessed this association in United Kingdom Biobank, a community-based cohort with >500,000 participants. The most common, mild AATD genotypes were associated neither with increased SARS-CoV-2 infection rates nor with increased SARS-CoV-2 fatalities, while the numbers of severe AATD cases were too low to allow definitive conclusions.


Assuntos
COVID-19/prevenção & controle , Predisposição Genética para Doença/genética , Deficiência de alfa 1-Antitripsina/genética , Doença Aguda , COVID-19/epidemiologia , COVID-19/mortalidade , Estudos de Coortes , Feminino , Humanos , Masculino , Mutação , Resultados Negativos , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/fisiologia , Doença Pulmonar Obstrutiva Crônica/genética , Enfisema Pulmonar/genética , Índice de Gravidade de Doença , Reino Unido/epidemiologia , alfa 1-Antitripsina/genética , alfa 1-Antitripsina/fisiologia
15.
BMC Ophthalmol ; 21(1): 194, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933006

RESUMO

BACKGROUND: Cytomegalovirus (CMV) has been known to cause unilateral corneal endotheliitis with keratic precipitates and localized corneal edema, iridocyclitis, and secondary glaucoma. CMV endotheliitis is diagnosed based on clinical manifestations and viral examination using qualitative polymerase chain reaction (PCR) of the aqueous humor. CASE PRESENTATION: An 80-year-old woman was referred to our department for bullous keratopathy. Pigmented keratic precipitates were found in the right eye without significant anterior chamber inflammation. After 8 months there was inflammation relapse with mutton fat keratic precipitates and PCR on aqueous humor was performed, with negative results for CMV, herpes simplex virus, and varicella zoster virus. Keratic precipitates disappeared with steroid instillation, and Descemet-stripping automated endothelial keratoplasty (DSAEK) was performed for the right eye. CMV-DNA was positive at 6.0 × 102 copies/ GAPDH 105 copies in real time PCR of corneal endothelial specimen removed during DSAEK with negative results for all the other human herpes viruses. After diagnosis of CMV corneal endotheliitis, treatment with systemic and topical ganciclovir was initiated and there was resolution of symptoms. No recurrence of iridocyclitis or corneal endotheliitis was observed at 6 months follow up. CONCLUSIONS: This case report suggests that PCR should be performed using the endothelium removed during DSAEK for bullous keratopathy of an unknown cause, even if PCR for aqueous humor yields negative results.


Assuntos
Infecções por Citomegalovirus , Infecções Oculares Virais , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Humor Aquoso , Citomegalovirus/genética , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , DNA Viral , Lâmina Limitante Posterior , Endotélio Corneano , Infecções Oculares Virais/diagnóstico , Infecções Oculares Virais/tratamento farmacológico , Feminino , Ganciclovir/uso terapêutico , Humanos , Resultados Negativos , Reação em Cadeia da Polimerase
17.
Endocrinol Diabetes Metab ; 4(2): e00148, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33855195

RESUMO

Aim: Obstructive sleep apnoea (OSA) is frequent in type 2 diabetes (T2D). The aim was to investigate the effect of a 12-week treatment with continuous positive airway pressure (CPAP) on glycaemic control assessed by continuous glucose monitoring (CGM), HbA1c and fasting blood glucose in patients with T2D and newly detected OSA. Methods: In a randomized controlled multicentre study, 72 participants with T2D and moderate to severe OSA (78% male, age 62 ± 7, AHI 35 ± 15) were recruited from outpatient clinics in three Danish hospitals and were randomized to CPAP intervention or control. The main outcome was glycaemic control assessed by 6 days CGM at baseline and after 12-week therapy, as well as by HbA1c and fasting blood glucose. Results: No significant changes were found in average glucose levels, time in glucose range, time with hypoglycaemia, time with hyperglycaemia or coefficient of variability. HbA1c decreased 0.7 mmol/mol (0.07%; P = .8) in the CPAP group and increased 0.8 mmol/mol (0.08%; P = .6) in the control group (intergroup difference, P = .6). Fasting blood glucose increased by 0.2 mmol/L (P = .02) in the CPAP group and by 0.4 mmol/L (P = .01) in the control group (intergroup difference, P = .7). In a prespecified subgroup analysis comparing participants with high adherence (minimum usage of four hours/night for 70% of all nights) to CPAP to the control group, no significant changes were observed either, although these participants had a tendency towards better glycaemic indices. Conclusions: CPAP treatment for 12 weeks does not significantly change glycaemic control in patients with type 2 diabetes and OSA.


Assuntos
Automonitorização da Glicemia , Glicemia , Pressão Positiva Contínua nas Vias Aéreas , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Controle Glicêmico , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/terapia , Idoso , Feminino , Hemoglobina A Glicada , Humanos , Masculino , Pessoa de Meia-Idade , Resultados Negativos , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/sangue , Fatores de Tempo
18.
Endocrinol Diabetes Metab ; 4(2): e00221, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33855221

RESUMO

Background: Calcium oxalate stones are the most common cause of nephrolithiasis in the United States. Smaller studies of <15 patients investigating ezetimibe, a selective cholesterol absorption inhibitor, have suggested increased urine oxalate levels with use of the drug. We attempt to better define this relationship of ezetimibe on urinary oxalate using a larger patient sample analysing multiple urine collections on and off treatment. Materials and Methods: We retrospectively reviewed all consecutive patients from 01/2018 through 04/2019 evaluated for nephrolithiasis with use of ezetimibe documented in their medical record at Mayo Clinic Florida. Primary outcomes included increase in urinary oxalate with use of ezetimibe and reduction in urinary oxalate with discontinuation of medication. Results: Of 57 reviewed patients, 30 (53%) met inclusion criteria yielding 117 24-h urine measurements either on ezetimibe (72 measurements) or off ezetimibe (41 measurements). The mean urinary oxalate level off ezetimibe was 39.86 mg versus 40.45 mg with ezetimibe. After adjusting for age and sex, the estimated difference was 1.239 mg (95% CI, -4.856 to 7.335 mg; p = 0.93). A subset of six patients with urinary oxalate values both on and off ezetimibe showed a difference in 24-h urinary oxalate levels ranged from -16.40 to 14.95 mg (mean difference = 0.93 mg; median difference = 3.84 mg). Conclusion: Use of ezetimibe does not provide clear evidence of a difference in urinary oxalate levels.


Assuntos
Anticolesterolemiantes/efeitos adversos , Ezetimiba/efeitos adversos , Oxalatos/urina , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultados Negativos , Nefrolitíase/induzido quimicamente , Nefrolitíase/prevenção & controle , Nefrolitíase/urina , Estudos Retrospectivos
19.
Sci Rep ; 11(1): 8272, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33859290

RESUMO

Type I interferon (IFN) dysregulation is a major contributory factor in the development of several autoimmune diseases, termed type I interferonopathies, and is thought to be the pathogenic link with chronic inflammation in these conditions. Anti-neutrophil cytoplasmic antibody (ANCA)-Associated Vasculitis (AAV) is an autoimmune disease characterised by necrotising inflammation of small blood vessels. The underlying biology of AAV is not well understood, however several studies have noted abnormalities in type I IFN responses. We hypothesised that type I IFN responses are systemically dysregulated in AAV, consistent with features of a type I interferonopathy. To investigate this, we measured the expression of seven interferon regulated genes (IRGs) (ISG15, SIGLEC1, STAT1, RSAD2, IFI27, IFI44L and IFIT1) in peripheral blood samples, as well as three type I IFN regulated proteins (CXCL10, MCP-1 and CCL19) in serum samples from AAV patients, healthy controls and disease controls. We found no difference in type I IFN regulated gene or protein expression between AAV patients and healthy controls. Furthermore, IRG and IFN regulated protein expression did not correlate with clinical measurements of disease activity in AAV patients. Thus, we conclude that systemic type I IFN responses are not key drivers of AAV pathogenesis and AAV should not be considered a type I interferonopathy.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/etiologia , Interferon Tipo I/fisiologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Quimiocina CCL2/sangue , Quimiocina CCL2/genética , Quimiocina CXCL10/sangue , Quimiocina CXCL10/genética , Citocinas/sangue , Citocinas/genética , Expressão Gênica/genética , Regulação da Expressão Gênica/genética , Humanos , Interferon Tipo I/metabolismo , Resultados Negativos , Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico/sangue , Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico/genética , Ubiquitinas/sangue , Ubiquitinas/genética
20.
Hum Antibodies ; 29(2): 109-113, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33720878

RESUMO

BACKGROUND: There are few studies to compare antibody response against anti-spike (S) and anti- nucleoprotein (N) SARS-CoV-2. OBJECTIVE: The aim of this study was to evaluate the IgG antibody production against S and N antigens of the virus and their correlation with the time and severity of the disease. METHODS: The IgG antibodies against S and N antigens of SARS-CoV-2 in serum specimens of 72 symptomatic patients who tested real-time reverse transcription polymerase chain reaction positive for SARS-CoV-2 were detected using the ELISA technique. Different antibody response was compared and the correlation with the time from disease onset and the severity was evaluated. RESULTS: Forty-eight of 72 (67%) patients tested positive for anti-SARS-CoV-2 antibodies, while 24 (33%) did not have detectable antibodies. Comparison of antibody levels for N and S antibodies showed that they correlate with each other well (r= 0.81; P< 0.001). However, sensitivity of anti-S SARS-CoV-2 IgG and anti-N SARS-CoV-2 IgG was 30% and 60%, during the first 7 days after symptom onset (r= 0.53; P= 0.111), but increased to 73% and 68% at more than 1-week post symptom onset (r= 0.89, P= 0.111), respectively. Cases with positive IgG response showed a decreased CD8+ T cells percentage compared to the negative IgG groups (26 ± 14 vs. 58 ± 32, p= 0.066 in anti-N IgG group and 28 ± 15 vs. 60 ± 45, p= 0.004 in anti-S IgG group, respectively). CONCLUSION: Nearly one-third of the confirmed COVID-19 patients had negative serology results. Lower percent positivity at early time points after symptom onset (less than 1 week) was seen using anti-S SARS-COV-2 IgG kit compare to the anti-N SARS-CoV-2 IgG; therefore, clinicians should interpret negative serology results of especially anti-S SARS-CoV-2 IgG with caution.


Assuntos
COVID-19/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Imunoglobulina G/análise , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , Idoso , Linfócitos T CD8-Positivos/imunologia , COVID-19/diagnóstico , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Subpopulações de Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Resultados Negativos , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Índice de Gravidade de Doença
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