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1.
Medicina (Kaunas) ; 57(5)2021 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-34065046

RESUMEN

Background and Objectives: This observational study aims to determine the correlation between glycemic control with the HbA1c value and adverse obstetric outcome in women affected by pre-gestational diabetes. Materials and Methods: A retrospective analysis has been performed at the University Hospital of Udine. Only patients with a singleton pregnancy, pre-gestational diabetes, and known level of Hb A1c throughout pregnancy were included in the study. Results: According to the HbA1c level, at the beginning of pregnancy, 49 patients with HbA1c ≤ 7.0% were compared with 45 patients with HbA1c > 7.0%. Maternal age at diagnosis of the disease was significantly higher in the group with HbA1c ≤ 7% than in the group with HbA1c > 7%, 26.00 (18.00-32.00) vs. 20.00 (12.50-27.00). Women with HbA1c ≤ 7.0% reached, at term of pregnancy, significantly lower levels of HbA1c, 5.8% (5.7-6.0) vs. 6.7% (6.3-7.3). Daily insulin units were statistically different between the two groups at the end of pregnancy (47.92 (39.00-67.30) vs. 64.00 (48.00-82.00)). Proteinuria was significantly higher in the group with HbA1c > 7.0%, who delivered at earlier gestational age (37.57 (35.57-38.00) vs. 38.14 (38.00-38.43). Moreover, women with HbA1c > 7.0% had a significantly higher prevalence of an adverse composite outcome. Of note, in multivariate logistic regression analysis, pregnancy complications were significantly correlated to pre-pregnancy HbA1c > 7.0% (OR 2.95 CI.95 1.16-7.48, p < 0.05) independently of age, insulin treatment, and type of diabetes. Conclusions: Our data, obtained from a single-center cohort study, suggest that starting pregnancy with poor glycemic control might predict more complex management of diabetes in the following trimesters.


Asunto(s)
Diabetes Gestacional , Resultado del Embarazo , Glucemia , Estudios de Cohortes , Diabetes Gestacional/tratamiento farmacológico , Diabetes Gestacional/epidemiología , Femenino , Hemoglobina A Glucada/análisis , Humanos , Embarazo , Resultado del Embarazo/epidemiología , Estudios Retrospectivos
2.
Nat Commun ; 12(1): 3394, 2021 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-34099641

RESUMEN

The large majority of variants identified by GWAS are non-coding, motivating detailed characterization of the function of non-coding variants. Experimental methods to assess variants' effect on gene expressions in native chromatin context via direct perturbation are low-throughput. Existing high-throughput computational predictors thus have lacked large gold standard sets of regulatory variants for training and validation. Here, we leverage a set of 14,807 putative causal eQTLs in humans obtained through statistical fine-mapping, and we use 6121 features to directly train a predictor of whether a variant modifies nearby gene expression. We call the resulting prediction the expression modifier score (EMS). We validate EMS by comparing its ability to prioritize functional variants with other major scores. We then use EMS as a prior for statistical fine-mapping of eQTLs to identify an additional 20,913 putatively causal eQTLs, and we incorporate EMS into co-localization analysis to identify 310 additional candidate genes across UK Biobank phenotypes.


Asunto(s)
Mapeo Cromosómico/métodos , Biología Computacional/métodos , Sitios de Carácter Cuantitativo , Aprendizaje Automático Supervisado , Adulto , Estudios de Cohortes , Conjuntos de Datos como Asunto , Perfilación de la Expresión Génica , Humanos , Polimorfismo de Nucleótido Simple
3.
Nat Commun ; 12(1): 3400, 2021 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-34099648

RESUMEN

Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as a marker of neurodegeneration in 13 neurodegenerative disorders, Down syndrome, depression and cognitively unimpaired controls from two multicenter cohorts: King's College London (n = 805) and the Swedish BioFINDER study (n = 1,464). Plasma NfL was significantly increased in all cortical neurodegenerative disorders, amyotrophic lateral sclerosis and atypical parkinsonian disorders. We demonstrate that plasma NfL is clinically useful in identifying atypical parkinsonian disorders in patients with parkinsonism, dementia in individuals with Down syndrome, dementia among psychiatric disorders, and frontotemporal dementia in patients with cognitive impairment. Data-driven cut-offs highlighted the fundamental importance of age-related clinical cut-offs for disorders with a younger age of onset. Finally, plasma NfL performs best when applied to indicate no underlying neurodegeneration, with low false positives, in all age-related cut-offs.


Asunto(s)
Disfunción Cognitiva/diagnóstico , Depresión/diagnóstico , Síndrome de Down/diagnóstico , Enfermedades Neurodegenerativas/diagnóstico , Proteínas de Neurofilamentos/líquido cefalorraquídeo , Factores de Edad , Anciano , Biomarcadores/líquido cefalorraquídeo , Disfunción Cognitiva/líquido cefalorraquídeo , Estudios de Cohortes , Depresión/líquido cefalorraquídeo , Síndrome de Down/líquido cefalorraquídeo , Reacciones Falso Positivas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Neurodegenerativas/líquido cefalorraquídeo , Valor Predictivo de las Pruebas , Valores de Referencia , Factores Sexuales
4.
Nat Commun ; 12(1): 3417, 2021 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-34099642

RESUMEN

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease.


Asunto(s)
Enfermedad de Alzheimer/genética , Herencia Multifactorial , Edad de Inicio , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/patología , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Apolipoproteínas E/genética , Estudios de Casos y Controles , Estudios de Cohortes , Conjuntos de Datos como Asunto , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Medición de Riesgo/métodos , Factores de Riesgo
5.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(5): 546-551, 2021 May.
Artículo en Chino | MEDLINE | ID: mdl-34112290

RESUMEN

OBJECTIVE: To analyze the effect of target-oriented treatment based on nutrition-oriented information software on nutritional standards of adult patients with severe traumatic brain injury (sTBI). METHODS: Adult patients with sTBI admitted to the department of emergency intensive care unit (EICU) of Huzhou First People's Hospital were enrolled. Taking the online time of information software as the node on March 1st 2019, the patients who underwent early standardized enteral nutrition (EN) process from March 1st 2018 to February 28th 2019 were taken as the control group. The patients who received nutrition management by the nutritional support management system software for critical patients from March 1st 2019 to February 29th 2020 were used as the experimental group. The software was integrated with critical information system software. The effects of nutritional support in two groups were evaluated, including starting time of EN; total energy supply, total protein supply, energy compliance rate on 7 days and 14 days; the total albumin. And the related indicators of critical illness management were evaluated, including the survival rate of intensive care unit (ICU) at 28 days, duration of invasive mechanical ventilation (IMV), successful rates of weaning from IMV, rapid shallow breath index (RSBI) after spontaneous breathing test (SBT), serum cholinesterase on 7 days and 14 days, etc. RESULTS: Fifty-one patients with sTBI were included in the analysis, 28 in the control group and 23 in the experimental group. There were no significant differences in baseline data between the two groups, such as gender, age, body mass index (BMI), acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, nutritional risk score (NUTRIC), etc., which were comparable. Compared with the control group, the starting time of EN in experimental group was significantly earlier (hours: 26.82±8.33 vs. 36.73±12.86, P = 0.046). The total protein supply on 7 days and 14 days [g×kg-1×d-1: 1.87 (1.36, 1.92) vs. 1.02 (0.87, 1.67), 2.63 (1.49, 1.92) vs. 1.23 (0.89, 1.92), both P < 0.05], the total energy supply on 14 days (kJ×kg-1×d-1: 154.26±68.16 vs. 117.99±112.42, P = 0.033), the energy compliance rate on 14 days [80.0% (16/20) vs. 35.7% (10/28), P = 0.002], and the serum cholinesterase on 14 days [U/L: 5 792.5 (4 621.0, 8 131.0) vs. 4 689.7 (3 639.0, 7 892.0), P = 0.048] in experimental group were significantly increased. There were no significant differences in other indicators between the two groups [total energy supply on 7 days (kJ×kg-1×d-1): 91.50±30.50 vs. 92.88±28.16, P = 0.184; energy compliance rate on 7 days: 34.7% (8/23) vs. 21.4% (6/28), P = 0.288; total albumin (g): 97.80±46.29 vs. 114.29±52.68, P = 0.086; 28-day survival rate of ICU: 87.0% vs. 78.6%, P = 0.081; duration of IMV (days): 14.33±7.68 vs. 15.68±6.82, P = 0.074; successful rates of weaning from IMV: 69.6% vs. 67.9%, P = 0.895; RSBI after SBT (breaths×min-1×L-1): 26.84±10.69 vs. 33.68±8.94, P = 0.052; serum cholinesterase on 7 days (U/L): 4 289.7 (2 868.0, 7 291.0) vs. 3 762.2 (2 434.0, 6 892.0), P = 0.078]. CONCLUSIONS: The development and clinical application of nutrition support information software is helpful for the standardized implementation of the nutritional support treatment process for adult patients with sTBI, which is worthy of further clinical research and promotion.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Respiración Artificial , Adulto , Lesiones Traumáticas del Encéfalo/terapia , Estudios de Cohortes , Humanos , Unidades de Cuidados Intensivos , Programas Informáticos
6.
Exp Dermatol ; 30 Suppl 1: 18-22, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-34085330

RESUMEN

The reported incidence of COVID-19 among cohorts of patients with inflammatory bowel and skin diseases under treatment with biologicals is low. Treatment may further modify disease severity as some biological modifiers, such as anakinra, are also proposed for the management of COVID-19 patients potentially providing HS patients with an advantage. The above preliminary evidence suggests that hidradenitis suppurativa (HS) does probably not provide an increased susceptibility for COVID-19 and that any susceptibility is unlikely to be modified negatively by treatment with biologicals. On the occasion of its 10th International Conference, experts of the European Hidradenitis Suppurativa Foundation e.V. have prepared a consensus statement regarding anti-COVID-19 measurements for HS patients. Based on the available knowledge, patients with HS may be vaccinated against SARS-CoV2 and patients affected by metabolic syndrome constitute a high-risk group for COVID-19 and should be vaccinated at the earliest convenient point in time. HS patients on treatment with adalimumab can be vaccinated with non-living virus anti-SARS-CoV2 vaccines. A possible suboptimal effect of the vaccine may be suspected but might not be expected universally. The management of the biological treatment in HS patients is at the discretion of the dermatologist / responsible physician.


Asunto(s)
COVID-19/complicaciones , Hidradenitis Supurativa/complicaciones , Hidradenitis Supurativa/tratamiento farmacológico , SARS-CoV-2 , Adalimumab/uso terapéutico , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/farmacología , Estudios de Cohortes , Susceptibilidad a Enfermedades , Europa (Continente) , Fundaciones , Hidradenitis Supurativa/inmunología , Humanos , Incidencia , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Síndrome Metabólico/complicaciones , Síndrome Metabólico/inmunología , Pandemias , Índice de Severidad de la Enfermedad
7.
Rev Bras Epidemiol ; 24: e210032, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34105595

RESUMEN

OBJECTIVE: To evaluate the association between dental visits and variation in the glycated hemoglobin index (A1C) of patients with type 2 diabetes (T2DM) with well or not well glycemic control over time. METHODS: Patients with T2DM, A1C ≥ 7% (not well-controlled) and < 7% (well-controlled), who attended a primary care service and were followed up from January 2010 to May 2018. The outcome was the variation of A1C obtained from reference laboratories. At the beginning of the study, a questionnaire with behavioral, clinical, and socioeconomic information was carried out. Multiple linear regression analyses tested interaction terms of all variables with the initial glycemic level (not well-controlled or well-controlled). RESULTS: The sample consisted of 507 people, 65% women, and 66% individuals 55 to 74 years old, followed on average for 5.4 years. There was an interaction (p = 0.01) between dental visits and initial A1C. Patients not well-controlled with at least one dental visit had an average reduction in A1C of -0.56 percentage point (95%CI -1.06 - -0.56), whereas the well-controlled group who also had at least one dental visit had an increase of 0.34 percentage point (95%CI -0.18 - 0.87). CONCLUSION: Dental visits were associated with an improvement in A1C of approximately a half-percentage point in patients who had the initial A1C considered as not well-controlled.


Asunto(s)
Diabetes Mellitus Tipo 2 , Anciano , Brasil , Estudios de Cohortes , Diabetes Mellitus Tipo 2/terapia , Femenino , Hemoglobina A Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Atención Primaria de Salud , Estudios Retrospectivos
8.
J Frailty Aging ; 10(3): 290-296, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34105715

RESUMEN

INTRODUCTION: The World Health Organization (WHO) has recently launched the term "intrinsic capacity", defined as "the composite of all the physical and mental capacities of an individual". Intrinsic capacity has a positive value towards healthy aging, and is constructed by five domains: cognition, vitality/nutrition, sensory, psychology, and mobility. ICOPE App and ICOPE Monitor are applications for the assessment (screening) of intrinsic capacity. HYPOTHESIS: Intrinsic capacity assessed by the ICOPE Apps at baseline could be associated with the incidence of frailty, functional decline, and health outcomes during 1-year follow-up. OBJECTIVES: To assess the association between intrinsic capacity measured by the ICOPE Apps at baseline and the incidence of frailty in community-dwelling older adults during 1-year follow-up. Secondarily, to assess the association of intrinsic capacity and functional decline, mortality, pre-frailty, falls, institutionalization, and quality of life. METHODS: Protocol for a cohort study of community-dwelling adults ≥65-year-old, with no other exclusion criteria than the inability to use the Apps or communicate by telephone/video-call for any reason (cognitive or limited access to telephone/video-call) OR being considered frail at baseline (defined as having a Rockwood's clinical frailty scale, CFS score ≥4). Intrinsic capacity measured by the ICOPE Apps and CFS will be assessed at baseline, 4-, 8- and 12-month follow-up by telephone/video-call. Assuming a prevalence of frailty of 10.7%, and incidence of 13% (alpha-risk=0.05), 400 participants at 12-month end-point (relative precision=0.10) and 600 participants at baseline will be required. RESULTS: Associations among the decrease in intrinsic capacity and higher risk of frailty, functional decline, and health adverse outcomes during 1-year follow-up are expected. CONCLUSIONS: ICOPE Apps might identify individuals at higher risk of frailty, functional decline, and health adverse outcomes. The implementation of the ICOPE Apps into clinical practice might help to deliver efficient person-centered care-plans, and benefit the healthcare systems.


Asunto(s)
Prestación Integrada de Atención de Salud , Aplicaciones Móviles , Anciano , Estudios de Cohortes , Anciano Frágil , Evaluación Geriátrica , Humanos , Vida Independiente , Atención Primaria de Salud , Calidad de Vida
9.
Cells ; 10(5)2021 05 05.
Artículo en Inglés | MEDLINE | ID: mdl-34062964

RESUMEN

A malfunction of the innate immune response in COVID-19 is associated with eosinopenia, particularly in more severe cases. This study tested the hypothesis that this eosinopenia is COVID-19 specific and is associated with systemic activation of eosinophils. Blood of 15 healthy controls and 75 adult patients with suspected COVID-19 at the ER were included before PCR testing and analyzed by point-of-care automated flow cytometry (CD10, CD11b, CD16, and CD62L) in the absence or presence of a formyl peptide (fNLF). Forty-five SARS-CoV-2 PCR positive patients were grouped based on disease severity. PCR negative patients with proven bacterial (n = 20) or other viral (n = 10) infections were used as disease controls. Eosinophils were identified with the use of the FlowSOM algorithm. Low blood eosinophil numbers (<100 cells/µL; p < 0.005) were found both in patients with COVID-19 and with other infectious diseases, albeit less pronounced. Two discrete eosinophil populations were identified in healthy controls both before and after activation with fNLF based on the expression of CD11b. Before activation, the CD11bbright population consisted of 5.4% (CI95% = 3.8, 13.4) of total eosinophils. After activation, this population of CD11bbright cells comprised nearly half the population (42.21%, CI95% = 35.9, 54.1). Eosinophils in COVID-19 had a similar percentage of CD11bbright cells before activation (7.6%, CI95% = 4.5, 13.6), but were clearly refractory to activation with fNLF as a much lower percentage of cells end up in the CD11bbright fraction after activation (23.7%, CI95% = 18.5, 27.6; p < 0.001). Low eosinophil numbers in COVID-19 are associated with refractoriness in responsiveness to fNLF. This might be caused by migration of fully functional cells to the tissue.


Asunto(s)
COVID-19/inmunología , Eosinófilos/inmunología , Inmunidad Innata , N-Formilmetionina Leucil-Fenilalanina/metabolismo , SARS-CoV-2/inmunología , Adulto , COVID-19/sangre , COVID-19/diagnóstico , COVID-19/virología , Prueba de Ácido Nucleico para COVID-19 , Estudios de Casos y Controles , Separación Celular , Estudios de Cohortes , Eosinófilos/metabolismo , Citometría de Flujo , Voluntarios Sanos , Humanos , Recuento de Leucocitos , ARN Viral/aislamiento & purificación , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la Enfermedad
10.
Int J Mol Sci ; 22(10)2021 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-34065289

RESUMEN

Genome-wide association studies (GWAS) found locus 3p21.31 associated with severe COVID-19. CCR5 resides at the same locus and, given its known biological role in other infection diseases, we investigated if common noncoding and rare coding variants, affecting CCR5, can predispose to severe COVID-19. We combined single nucleotide polymorphisms (SNPs) that met the suggestive significance level (P ≤ 1 × 10-5) at the 3p21.31 locus in public GWAS datasets (6406 COVID-19 hospitalized patients and 902,088 controls) with gene expression data from 208 lung tissues, Hi-C, and Chip-seq data. Through whole exome sequencing (WES), we explored rare coding variants in 147 severe COVID-19 patients. We identified three SNPs (rs9845542, rs12639314, and rs35951367) associated with severe COVID-19 whose risk alleles correlated with low CCR5 expression in lung tissues. The rs35951367 resided in a CTFC binding site that interacts with CCR5 gene in lung tissues and was confirmed to be associated with severe COVID-19 in two independent datasets. We also identified a rare coding variant (rs34418657) associated with the risk of developing severe COVID-19. Our results suggest a biological role of CCR5 in the progression of COVID-19 as common and rare genetic variants can increase the risk of developing severe COVID-19 by affecting the functions of CCR5.


Asunto(s)
COVID-19/genética , COVID-19/metabolismo , Predisposición Genética a la Enfermedad , Receptores CCR5/genética , Receptores CCR5/metabolismo , Alelos , Bronquios/metabolismo , Bronquios/patología , Bronquios/virología , COVID-19/fisiopatología , Cromosomas Humanos/genética , Estudios de Cohortes , Biología Computacional , Bases de Datos Genéticas , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Pulmón/metabolismo , Pulmón/patología , Pulmón/virología , Polimorfismo de Nucleótido Simple , Secuenciación del Exoma Completo
11.
Viruses ; 13(5)2021 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-34068899

RESUMEN

The use of rapid antigenic tests (Ag-RDTs) to diagnose a SARS-CoV-2 infection has become a common practice recently. This study aimed to evaluate performance of Abbott PanbioTM Ag-RDTs with regard to nucleic acid amplification testing (NAAT) in the early stages of the disease. A cohort of 149,026 infected symptomatic patients, reported in Catalonia from November 2020 to January 2021, was selected. The positivity rates of the two tests were compared with respect to the dates of symptom onset. Ag-RDTs presented positivity rates of 84% in the transmission phases of the disease and 31% in the pre-symptomatic period, compared to 93% and 91%, respectively, for NAAT. The detection of many false negatives with Ag-RDTs during the pre-symptomatic period demonstrates the risk of virus dissemination with this diagnostic technique if used outside the symptomatic period.


Asunto(s)
Prueba de Ácido Nucleico para COVID-19/métodos , Prueba Serológica para COVID-19/métodos , COVID-19/diagnóstico , SARS-CoV-2/aislamiento & purificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos Virales/inmunología , Enfermedades Asintomáticas , Niño , Preescolar , Estudios de Cohortes , Reacciones Falso Negativas , Reacciones Falso Positivas , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Técnicas de Amplificación de Ácido Nucleico/métodos , Sensibilidad y Especificidad , España , Adulto Joven
12.
Medicina (Kaunas) ; 57(5)2021 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-34069202

RESUMEN

Background and Objectives: The susceptibility of pregnant patients at term to SARS-CoV-2 infection regarding the ABO and Rh blood group polymorphism was analyzed in this study. Materials and Methods: In this prospective study, 457 patients admitted for delivery at term in our hospital, between 1 April 2020 and 31 December 2020 were studied. There were 46 positive and 411 SARS-CoV-2 negative patients. Their values for RT-PCR, ABO, and Rh blood group analyses, which were determined upon admittance, were studied. Results: A slightly higher percentage of infected pregnant patients at term belonged to the A blood group compared with the percentage belonging to the other blood groups; this was also true for the healthy control group. For the Rh-negative pregnant patients at term, the odds of being infected with SARS-CoV-2 was OR = 1.22 compared with Rh-positive patients where OR = 1. In our study, the highest risk was found among BIII Rh-negative pregnant patients at term (OR = 3). None of the above differences were statistically significant. Conclusions: No significant difference was found between the percentage of ABO or Rh blood groups in SARS-CoV-2 positive patients when compared with SARS-CoV-2 negative patients (p = 0.562).


Asunto(s)
Antígenos de Grupos Sanguíneos , COVID-19 , Estudios de Cohortes , Femenino , Humanos , Embarazo , Estudios Prospectivos , Factores de Riesgo , SARS-CoV-2
13.
Int J Mol Sci ; 22(10)2021 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-34070214

RESUMEN

During tubo-ovarian high-grade serous carcinoma (HGSC) progression, tumoral cells undergo phenotypic changes in their epithelial marker profiles, which are essential for dissemination processes. Here, we set out to determine whether standard epithelial markers can predict HGSC patient prognosis. Levels of E-CADH, KRT7, KRT18, KRT19 were quantified in 18 HGSC cell lines by Western blot and in a Discovery cohort tissue microarray (TMA) (n = 101 patients) using immunofluorescence. E-CADH and KRT7 levels were subsequently analyzed in the TMA of the Canadian Ovarian Experimental Unified Resource cohort (COEUR, n = 1158 patients) and in public datasets. Epithelial marker expression was highly variable in HGSC cell lines and tissues. In the Discovery cohort, high levels of KRT7 and KRT19 were associated with an unfavorable prognosis, whereas high E-CADH expression indicated a better outcome. Expression of KRT7 and E-CADH gave a robust combination to predict overall survival (OS, p = 0.004) and progression free survival (PFS, p = 5.5 × 10-4) by Kaplan-Meier analysis. In the COEUR cohort, the E-CADH-KRT7 signature was a strong independent prognostic biomarker (OS, HR = 1.6, p = 2.9 × 10-4; PFS, HR = 1.3, p = 0.008) and predicted a poor patient response to chemotherapy (p = 1.3 × 10-4). Our results identify a combination of two epithelial markers as highly significant indicators of HGSC patient prognosis and treatment response.


Asunto(s)
Antígenos CD/metabolismo , Biomarcadores de Tumor/metabolismo , Cadherinas/metabolismo , Cistadenocarcinoma Seroso/metabolismo , Neoplasias de las Trompas Uterinas/metabolismo , Queratina-7/metabolismo , Neoplasias Ováricas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Línea Celular Tumoral , Estudios de Cohortes , Cistadenocarcinoma Seroso/mortalidad , Neoplasias de las Trompas Uterinas/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Queratina-19/metabolismo , Neoplasias Pulmonares/metabolismo , Persona de Mediana Edad , Neoplasias Ováricas/mortalidad , Pronóstico , Supervivencia sin Progresión , Neoplasias Gástricas/metabolismo , Vimentina/metabolismo
14.
Nat Commun ; 12(1): 3289, 2021 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-34078897

RESUMEN

Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked to acute stroke severity (National Institute of Health Stroke Scale). This framework was developed in 555 patients (38% female). Findings were validated in an independent cohort (n = 503, 41% female). Here, we show brain lesions in regions subserving motor and language functions help explain stroke severity in both men and women, however more widespread lesion patterns are relevant in female patients. Higher stroke severity in women, but not men, is associated with left hemisphere lesions in the vicinity of the posterior circulation. Our results suggest there are sex-specific functional cerebral asymmetries that may be important for future investigations of sex-stratified approaches to management of acute ischemic stroke.


Asunto(s)
Tronco Encefálico/patología , Accidente Cerebrovascular Isquémico/patología , Corteza Sensoriomotora/patología , Tálamo/patología , Anciano , Anciano de 80 o más Años , Teorema de Bayes , Mapeo Encefálico , Tronco Encefálico/irrigación sanguínea , Tronco Encefálico/diagnóstico por imagen , Revascularización Cerebral/métodos , Estudios de Cohortes , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/terapia , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Factores de Riesgo , Corteza Sensoriomotora/irrigación sanguínea , Corteza Sensoriomotora/diagnóstico por imagen , Índice de Severidad de la Enfermedad , Factores Sexuales , Tálamo/irrigación sanguínea , Tálamo/diagnóstico por imagen , Resultado del Tratamiento
15.
Medicine (Baltimore) ; 100(22): e26252, 2021 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-34087914

RESUMEN

ABSTRACT: Suicide is an increasingly serious public health care concern worldwide. The impact of decreased in-house psychiatric resources on emergency care for suicidal patients has not been thoroughly examined. We evaluated the effects of closing an in-hospital psychiatric ward on the prehospital and emergency ward length of stay (LOS) and disposition location in patients who attempted suicide.This was a retrospective before-and-after study at a community emergency department (ED) in Japan. On March 31, 2014, the hospital closed its 50 psychiatric ward beds and outpatient consultation days were decreased from 5 to 2 days per week. Electronic health record data of suicidal patients who were brought to the ED were collected for 5 years before the decrease in in-hospital psychiatric services (April 1, 2009-March 31, 2014) and 5 years after the decrease (April 1, 2014-March 31, 2019). One-to-one propensity score matching was performed to compare prehospital and emergency ward LOS, and discharge location between the 2 groups.Of the 1083 eligible patients, 449 (41.5%) were brought to the ED after the closure of the psychiatric ward. Patients with older age, burns, and higher comorbidity index values, and those requiring endotracheal intubation, surgery, and emergency ward admission, were more likely to receive ED care after the psychiatric ward closure. In the propensity matched analysis with 418 pairs, the after-closure group showed a significant increase in median prehospital LOS (44.0 minutes vs 51.0 minutes, P < .001) and emergency ward LOS (3.0 days vs 4.0 days, P = .014) compared with the before-closure group. The rate of direct home return was significantly lower in the after-closure group compared with the before-closure group (87.1% vs 81.6%, odds ratio: 0.66; 95% confidence interval: 0.45-0.96).The prehospital and emergency ward LOS for patients who attempted suicide in the study site increased significantly after a decrease in hospital-based mental health services. Conversely, there was significant reduction in direct home discharge after the decrease in in-house psychiatric care. These results have important implications for future policy to address the increasing care needs of patients who attempt suicide.


Asunto(s)
Servicio de Urgencia en Hospital/estadística & datos numéricos , Clausura de las Instituciones de Salud/estadística & datos numéricos , Hospitales Comunitarios/estadística & datos numéricos , Intento de Suicidio/psicología , Adulto , Estudios de Casos y Controles , Estudios de Cohortes , Desinstitucionalización/estadística & datos numéricos , Servicios Médicos de Urgencia/normas , Servicios Médicos de Urgencia/estadística & datos numéricos , Femenino , Clausura de las Instituciones de Salud/legislación & jurisprudencia , Hospitalización/estadística & datos numéricos , Humanos , Japón/epidemiología , Tiempo de Internación/estadística & datos numéricos , Masculino , Servicios de Salud Mental/economía , Servicios de Salud Mental/legislación & jurisprudencia , Servicios de Salud Mental/estadística & datos numéricos , Persona de Mediana Edad , Alta del Paciente/estadística & datos numéricos , Servicio de Psiquiatría en Hospital/economía , Servicio de Psiquiatría en Hospital/organización & administración , Derivación y Consulta/estadística & datos numéricos , Estudios Retrospectivos , Intento de Suicidio/estadística & datos numéricos
16.
Zhonghua Gan Zang Bing Za Zhi ; 29(5): 446-450, 2021 May 20.
Artículo en Chino | MEDLINE | ID: mdl-34107582

RESUMEN

Objective: To analyze the time point when patients with fatty liver disease had a significantly higher risk of elevated fasting blood glucose than those without in the physical examination group in Karamay Central Hospital, factors affecting the incidence of elevated blood glucose in patients with fatty liver disease, and the influence of the number of influencing factors on it. Methods: Physical examination data from Karamay Central Hospital during September 2008 to April 2017 were retrospectively analyzed. Combined with the survival analysis, the 1-,3-, 5-, and 7-year prevalence rates of elevated fasting glucose occurs in people with and without fatty liver disease were analyzed. Z-test was used to compare the survival rate difference at each time point. Cox regression model was used for multivariate analysis. Results: 10 802 people were in the fatty liver group. The elevated fasting blood glucose incidence density was 61/1 000 person-years, and the 1-, 3-, 5-, and 7-year prevalence rates were 2%, 16%, 28%, and 38%, respectively. 29 579 people were in the non-fatty liver group. The elevated fasting blood glucose incidence density was 23/1000 person-years, and the 1-, 3-, 5-, and 7-year prevalence rates were 1%, 7%, 11%, and 16%, respectively. The short-term and long-term elevated fasting blood glucose incidence risk were significantly higher in fatty liver group than non-fatty liver group(P < 0.001). The elevated fasting blood glucose incidence risk was apparently higher in fatty liver group than that of non-fatty liver group from the first year onward (P < 0.001). Age≥50 year's old (HR = 1.954, 95% CI :1.792-2.132), elevated body mass index (HR = 1.397, 95% CI : 1.198-1.629), blood pressure (HR = 1.284, 95% CI : 1.181-1.397), triglycerides (HR = 1.171, 95% CI: 1.077-1.274) were independent risk factors, which promoted the elevated fasting blood glucose incidence risk in patients with fatty liver disease. Fatty liver combined with the above 2, 3, and 4 risk factors had apparently increased the incidence risk of elevated fasting blood glucose (P < 0.001). Conclusion: People with fatty liver disease had a higher risk of elevated fasting blood glucose from the first year than those without. Age≥50 year's old, elevated blood pressure, body mass index and triglyceride might increase risk of elevated fasting blood glucose in patients with fatty liver disease, combined with the above 2,3 or 4 risk factors can increase the risk of elevated fasting blood glucose.


Asunto(s)
Glucemia , Ayuno , Índice de Masa Corporal , Estudios de Cohortes , Humanos , Incidencia , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo
17.
Sensors (Basel) ; 21(10)2021 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-34068938

RESUMEN

Understanding periods of the year associated with higher risk for falling and less physical activity may guide fall prevention and activity promotion for older adults. We examined the relationship between weather and seasons on falls and physical activity in a three-year cohort of older adults with glaucoma. Participants recorded falls information via monthly calendars and participated in four one-week accelerometer trials (baseline and per study year). Across 240 participants, there were 406 falls recorded over 7569 person-months, of which 163 were injurious (40%). In separate multivariable regression models incorporating generalized estimating equations, temperature, precipitation, and seasons were not significantly associated with the odds of falling, average daily steps, or average daily active minutes. However, every 10 °C increase in average daily temperature was associated with 24% higher odds of a fall being injurious, as opposed to non-injurious (p = 0.04). The odds of an injurious fall occurring outdoors, as opposed to indoors, were greater with higher average temperatures (OR per 10 °C = 1.46, p = 0.03) and with the summer season (OR = 2.69 vs. winter, p = 0.03). Falls and physical activity should be understood as year-round issues for older adults, although the likelihood of injury and the location of fall-related injuries may change with warmer season and temperatures.


Asunto(s)
Accidentes por Caídas , Glaucoma , Accidentes por Caídas/prevención & control , Anciano , Estudios de Cohortes , Ejercicio Físico , Humanos , Estudios Prospectivos , Estaciones del Año , Tiempo (Meteorología)
18.
BMC Musculoskelet Disord ; 22(1): 506, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-34074293

RESUMEN

BACKGROUND: To evaluate the effect of treatment on serum bone biomarkers and explore whether serum bone biomarkers are associated with therapeutic response in rheumatoid arthritis (RA) patients treated with abatacept. METHODS: We enrolled 59 RA patients treated with abatacept from a multicenter, exploratory, short-term, prospective and observational ultrasound cohort study of patients who received biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) therapy. We evaluated the patients' clinical disease activity and musculoskeletal ultrasound (MSUS) scores. The serum concentrations of five bone biomarkers were evaluated (dickkopf-1 [Dkk-1], sclerostin [SOST], osteocalcin [OC], osteopontin [OPN], and osteoprotegerin [OPG]) by multiplex bead assays at baseline, 3, and 6 months: the change over 6 months was defined as the Δ value. 'Power Doppler (PD) responder' was defined as a patient whose Δtotal PD score over 6 months was greater than the median change. RESULTS: Abatacept significantly improved the clinical disease activity and MSUS score over 6 months. Serum OPG was significantly elevated at 6 months after the abatacept introduction (p = 0.016). The ΔSOST and ΔOPG were significantly greater in the PD responders versus the non-PD responders (p = 0.0041 and 0.0073, respectively). The serum Dkk-1 at baseline was significantly lower in the PD responders (n = 30) vs. the non-PD responders (n = 29) (p = 0.026). A multivariate logistic regression analysis showed that the serum Dkk-1 at baseline (odds ratio 0.50, 95% confidence interval [CI] 0.23-0.91, p = 0.043) was an independent predictor of PD responder status. CONCLUSION: Serum levels of bone biomarkers may be useful for predicting RA patients' therapeutic responses to abatacept. TRIAL REGISTRATION: Name of the registry: Assessment of therapeutic responsiveness by imaging of the joints in patients with rheumatoid arthritis; A observational cohort study Trial registration number: UMIN000012524 Date of registration: 12/9/2013 URL of trial registry record: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000014657.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Abatacept/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/tratamiento farmacológico , Biomarcadores , Estudios de Cohortes , Humanos , Japón , Estudios Prospectivos , Resultado del Tratamiento
19.
BMC Health Serv Res ; 21(1): 552, 2021 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-34090431

RESUMEN

BACKGROUND: Little is known about how continuity of care for hospitalized patients varies among hospitals. We describe the number of different general internal medicine physicians seeing hospitalized patients during a medical admission and how that varies by hospital. METHODS: We conducted a retrospective study of a national 20% sample of Medicare inpatients from 01/01/16 to 12/31/18. In patients with routine medical admissions (length of stay of 3-6 days, no Intensive Care Unit stay, and seen by only one generalist per day), we assessed odds of receiving all generalist care from one generalist. We calculated rates for each hospital, adjusting for patient and hospital characteristics in a multi-level logistic regression model. RESULTS: Among routine medical admissions with 3- to 6-day stays, only 43.1% received all their generalist care from the same physician. In those with a 3-day stay, 50.1% had one generalist providing care vs. 30.8% in those with a 6-day stay. In a two-level (admission and hospital) logistic regression model controlling for patient characteristics and length of stay, the odds of seeing just one generalist did not vary greatly by patient characteristics such as age, race/ethnicity, comorbidity or reason for admission. There were large variations in continuity of care among different hospitals and geographic areas. In the highest decile of hospitals, the adjusted mean percentage of patients receiving all generalist care from one physician was > 84.1%, vs. < 24.1% in the lowest decile. This large degree of variation persisted when hospitals were stratified by size, ownership, location or teaching status. CONCLUSIONS: Continuity of care provided by generalist physicians to medical inpatients varies widely among hospitals. The impact of this variation on quality of care is unknown.


Asunto(s)
Hospitales , Medicare , Anciano , Estudios de Cohortes , Continuidad de la Atención al Paciente , Estudios Transversales , Humanos , Estudios Retrospectivos , Estados Unidos
20.
J Pak Med Assoc ; 71(5): 1394-1398, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34091621

RESUMEN

OBJECTIVE: To evaluate the influence of certain genetic modifiers on foetal haemoglobin levels in thalassemia major and thalassemia intermedia. METHODS: The cohort study was conducted from November 2018 to August 2019, at Department of Haematology, University of Health Sciences, Lahore and comprised beta thalassemia intermedia and thalassemia major patients who were referred by various healthcare facilities across Punjab, Pakistan. Foetal haemoglobin was quantified by high performance liquid chromatography. Primary mutation analysis and single nucleotide polymorphisms were done by amplification refractory mutation system-based polymerase chain reaction. Data was analysed using SPSS 20. RESULTS: Of the 116 patients, 52(45%) had beta thalassemia intermedia and 64(55%) had thalassemia major. Foetal haemoglobin levels were primarily influenced by alleles of the HBG2 (rs7482144) and BCL11A (rs766432) genes, but single nucleotide polymorphism of HBS1L-MYB (rs9399137) had no significant role (p>0.05). The rs7482144 single nucleotide polymorphism explained 8.3% of the variation in the foetal haemoglobin levels, while 5% of trait variation was explained by rs766432. CONCLUSIONS: There was found a clear association between foetal haemoglobin level and single nucleotide polymorphisms in HBG2 (rs7482144) and BCL11A (rs766432) genes. This correlation was additive and was seen both in thalassemia major and thalassemia intermedia cohorts.


Asunto(s)
Talasemia beta , Proteínas Portadoras/genética , Estudios de Cohortes , Hemoglobina Fetal/genética , Humanos , Proteínas Nucleares/genética , Pakistán , Polimorfismo de Nucleótido Simple , Proteínas Represoras , Talasemia beta/genética
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