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INTRODUCTION: People with type 2 diabetes mellitus (DM2) have a higher prevalence of frailty compared to those without DM2. However, there is a lack of consensus on the diagnosis and clinical management of frail individuals with DM2. OBJECTIVES: This study aims to identify limitations and current needs in the use of the frailty concept in PCDM2 (people with DM2), as well as define and evaluate the dimensions that should be included in its routine clinical assessment. METHODS: A multidisciplinary team of eight health professionals from different hospitals in Spain participated in a process based on the nominal group technique. RESULTS: The study identified eight limitations in the assessment of frailty in PCDM2, categorized by importance, and 10 unmet needs related to the diagnosis and follow-up of the disease. Additionally, seven dimensions were identified that should be included in the definition of frail individuals with DM2, prioritized by importance and novelty. CONCLUSIONS: This article aims to increase knowledge and usage of the frailty concept in individuals with DM2 within the medical community. It also suggests the potential for future projects to develop a consensus definition of frailty tailored to this specific group.
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Diabetes Mellitus Tipo 2 , Fragilidade , Humanos , Idoso , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Idoso Fragilizado , Prevalência , ConsensoRESUMO
BACKGROUND: Circulating tumor DNA (ctDNA) sequencing is a promising approach for tailoring therapy in patients with cancer. We report hereby the results from a prospective study where we investigated the impact of comprehensive molecular profiling of ctDNA in patients with advanced solid tumors. PATIENTS AND METHODS: Genomic analysis was performed using the FoundationOne Liquid CDx Assay [324 genes, tumor mutational burden (TMB), microsatellite instability status]. Each individual genomic report was reviewed and discussed weekly by a multidisciplinary tumor board (MTB). Actionable targets were classified by ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) tier leading to molecular-based treatment suggestions wherever it was possible. RESULTS: Between December 2020 and November 2021, 1772 patients with metastatic solid tumors underwent molecular profiling. Median time to assay results was 12 days. Results were contributive for 1658 patients (94%). At least one actionable target was detected in 1059 patients (64%) with a total of 1825 actionable alterations including alteration of the DNA damage repair response pathway (n = 336, 18%), high TMB (>16 mutations/Mb; n = 243, 13%), PIK3CA mutations (n = 150, 8%), ERBB family pathway alterations (n = 127, 7%), PTEN alterations (n = 95, 5%), FGFR alterations (n = 67, 4%) and MET activations (n = 13, 0.7%). The MTB recommended a matched therapy for 597 patients (56%) with a total of 819 therapeutic orientations: clinical trials (n = 639, 78%), off-label/compassionate use (n = 81, 10%), approved drug (n = 51, 6%), and early access program (n = 48, 6%). In total, 122 patients (21%) were treated. Among the assessable patients (n = 107), 4 (4%) had complete response, 35 (33%) had partial response, 27 (25%) had stable disease, and 41 (38%) a progressive disease as best response. The median progression-free survival and median overall survival were 4.7 months (95% confidence interval 2.7-6.7 months) and 8.3 months (95% confidence interval 4.7-11.9 months) respectively. CONCLUSIONS: ctDNA sequencing with a large panel is an efficient approach to match patients with advanced cancer with targeted therapies.
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DNA Tumoral Circulante , Neoplasias , Humanos , DNA Tumoral Circulante/genética , Medicina de Precisão/métodos , Estudos Prospectivos , Neoplasias/tratamento farmacológico , Neoplasias/genética , DNA de Neoplasias/genética , Biomarcadores Tumorais/genética , Mutação , Sequenciamento de Nucleotídeos em Larga Escala/métodosRESUMO
The magnetic nature of the formation of solar active regions lies at the heart of understanding solar activity and, in particular, solar eruptions. A widespread model, used in many theoretical studies, simulations and the interpretation of observations, is that the basic structure of an active region is created by the emergence of a large tube of pre-twisted magnetic field. Despite plausible reasons and the availability of various proxies suggesting the accuracy of this model, there has not yet been a methodology that can clearly and directly identify the emergence of large pre-twisted magnetic flux tubes. Here, we present a clear signature of the emergence of pre-twisted magnetic flux tubes by investigating a robust topological quantity, called magnetic winding, in solar observations. This quantity detects the emerging magnetic topology despite the significant deformation experienced by the emerging magnetic field. Magnetic winding complements existing measures, such as magnetic helicity, by providing distinct information about field line topology, thus allowing for the direct identification of emerging twisted magnetic flux tubes.
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This position paper describes the most relevant and essential aspects of a comprehensive, multidimensional assessment of hospitalized elderly people. The change in demographic patterns and the epidemiological profiles of diseases makes it necessary for internal medicine departments to adapt in order to take into account the vulnerabilities of the elderly in this context. A comprehensive, multidimensional assessment and the multidisciplinary development of a care plan during hospitalization can have an impact in terms of preventing mortality, disability, and institutionalization at discharge. It is necessary for all internists to acquire skills to improve the hospitalization experience in the elderly and obtain better health outcomes in our patients. This document has been developed by the Focus Group on Aging and the Polypathological and Advanced Age Working Group and endorsed by the Spanish Society of Internal Medicine.
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Hospitalização , Medicina Interna , Idoso , Humanos , Envelhecimento , EspanhaRESUMO
This position paper describes the most relevant and essential aspects of a comprehensive, multidimensional assessment of hospitalized elderly people. The change in demographic patterns and the epidemiological profiles of diseases makes it necessary for internal medicine departments to adapt in order to take into account the vulnerabilities of the elderly in this context. A comprehensive, multidimensional assessment and the multidisciplinary development of a care plan during hospitalization can have an impact in terms of preventing mortality, disability, and institutionalization at discharge. It is necessary for all internists to acquire skills to improve the hospitalization experience in the elderly and obtain better health outcomes in our patients. This document has been developed by the Focus Group on Aging and the Polypathological and Advanced Age Working Group and endorsed by the Spanish Society of Internal Medicine.
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Heterogeneous photocatalysis is a promising technology to treat many industrial wastewaters. To date, this potential has not been proven with wastewaters from agricultural origins, such as swine wastewater. In this work, the photocatalytic degradation of swine wastewater was studied by applying a response surface methodology based on the Box-Behnken design. The interactive effects of the variation of factors such as photocatalyst dosage (X1), wastewater concentration (X2), and irradiation time (X3) were analyzed to identify the optimal operating conditions for COD reduction. A second-order polynomial accurately represented organics degradation with a high adjusted R-squared (0.9666). The main effects of factor X2 and the quadratic effects of factors X2 and X3 were the most significant for COD reduction. The optimal conditions for COD degradation were 1.16 g L-1 for photocatalyst dosage, 1.68% for wastewater concentration, and irradiation time of 9.2 h. These results have been validated in a confirmation experiment and COD removal reached 91.7% (98.1 % predicted). Based on the Langmuir-Hinshelwood model, the reaction rate constant was 3.9×10-3 min-1. Besides, FTIR analysis indicated that Aeroxide® TiO2 reusability may be possible, especially for low wastewater concentrations. Heterogeneous photocatalysis can be applied as a technology for the integrated treatment of industrial wastewaters resulting from swine production.
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Geena 2 is a tool for filtering, averaging, and aligning MALDI/TOF mass spectra, designed to assist scientists in the analysis of high volumes of data and support them for comparative studies. Three web interfaces are available with different levels of complexity. In this manuscript, we explain how to use Geena 2 with these three interfaces to perform analyses of one's own data. Two support protocols showing how to check the example input file and how to create an input file with own data are also presented. © 2018 by John Wiley & Sons, Inc.
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Software , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Guias como Assunto , Interface Usuário-ComputadorRESUMO
Renal osteodystrophy is a common complication of end-stage renal failure patients. It's most severe osseous complication is characterized by massive thickening of the cranial vault and facial bones, called uremic leontiasis ossea (ULO), with only few cases reported in the literature. A case of a 47-year-old female patient with ULO is presented. Physical examination showed enlargement of the jaws, which hinders proper ventilation and feeding. The computed tomography examination showed marked osseous proliferation in the jaws causing severe bony expansion and loss of normal bony architecture in the skull and the skull base. The most relevant clinical, histopathological and laboratory findings are discussed. The uremic leontiasis ossea causes significant aesthetic and functional changes. Correct diagnosis and management of the factors responsible for the development of bone lesions due to altered bone metabolism are key factors. The maxillofacial surgeon must have the proper knowledge of patient's medical condition and bone maturation status to address an adequate surgical strategy.
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Distúrbio Mineral e Ósseo na Doença Renal Crônica , Hiperostose Frontal Interna , Falência Renal Crônica , Estética Dentária , Ossos Faciais , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Markov state models (MSM) are used to model the kinetics of processes sampled by molecular dynamics (MD) simulations. MSM reduce the high dimensionality inherent to MD simulations as they partition the free energy landscape into discrete states, generating a kinetic model as a series of uncorrelated jumps between states. Here, we detail a new method, called GRadient Adaptive Decomposition, which optimizes coarse-grained MSM by refining borders with respect to the gradient along the free energy surface. The proposed method requires only a small number of initial microstates because it corrects for errors produced by limited sampling. Whereas many methods rely on fuzzy partitions for proper statistics, GRAD retains a crisp decomposition. Two test studies are presented to illustrate the method and assess its accuracy: the first analyzes MSM of idealized model potentials, while the second is a study of the dynamics of unstacking of the deoxyribose adenosine monophosphate dinucleotide.
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Cadeias de Markov , Simulação de Dinâmica Molecular , Nucleotídeos de Adenina/química , Nucleotídeos de Adenina/metabolismo , TermodinâmicaRESUMO
BACKGROUND: Chemotherapy is considered the most appropriate treatment for metastatic uterine sarcoma, despite its limited efficacy. No other treatment has been conclusively proved to be a real alternative, but some reports suggest that anti-hormonal therapy could be active in a small subset of patients. We report the case of a patient with metastatic uterine carcinosarcoma with positive hormonal receptors and a complete pathological response. CASE PRESENTATION: A 54-year-old white woman presented to our emergency room with hypovolemic shock and serious vaginal bleeding. After stabilization, she was diagnosed as having a locally advanced uterine carcinosarcoma with lymph nodes and bone metastatic disease. In order to control the bleeding, palliative radiotherapy was administered. Based on the fact that positive hormone receptors were found in the biopsy, non-steroidal aromatase inhibitor therapy with letrozole was started. In the following weeks, her general status improved and restaging imaging tests demonstrated a partial response of the primary tumor. Ten months after initiating aromatase inhibitor therapy, she underwent a radical hysterectomy and the pathological report showed a complete response. After completing 5 years of treatment, aromatase inhibitor therapy was stopped. She currently continues free of disease, without further therapy, and maintains a normal and active life. CONCLUSIONS: This case shows that patients with uterine carcinosarcoma and positive hormone receptors may benefit from aromatase inhibitor therapy. A multidisciplinary strategy that includes local therapies such as radiation and/or surgery should be considered the mainstay of treatment. Systemic therapies such as hormone inhibitors should be taken into consideration and deserve further clinical research in the era of precision medicine.
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Inibidores da Aromatase/uso terapêutico , Transtornos da Coagulação Sanguínea/complicações , Neoplasias Ósseas/tratamento farmacológico , Carcinossarcoma/complicações , Carcinossarcoma/tratamento farmacológico , Nitrilas/uso terapêutico , Triazóis/uso terapêutico , Neoplasias Uterinas/complicações , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Ósseas/secundário , Carcinossarcoma/diagnóstico , Carcinossarcoma/patologia , Feminino , Humanos , Letrozol , Metástase Linfática , Pessoa de Meia-Idade , Indução de Remissão , Choque/etiologia , Hemorragia Uterina/etiologia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/patologiaRESUMO
Many different materials have been tested for ß-glucosidases immobilization. Such materials, however, often show a poor activity related to a low surface area of the support or even enzyme hindrance caused by entrapment inside porous matrix. In this context, the use of nanosized zeolites as enzymes support is quite new and may be an interesting alternative. The present work evaluates the immobilization of ß-glucosidases in nanosized silicalites by covalent coupling. The new biocatalyst was able to convert 100% of cellobiose into glucose in 18 h at 50 °C and pH 5, retaining 85% of its activity after five cycles of reuse. A detailed investigation of the published literature indicates that, apparently, this is the first work concerning the immobilization of ß-glucosidases on nanosized zeolites ever reported.
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Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Nanoestruturas/química , Silicatos/química , beta-Glucosidase/química , beta-Glucosidase/metabolismo , Biocatálise , Hidrólise , Propriedades de SuperfícieRESUMO
The space charge accumulation phenomenon has garnered great interest over the last two decades because of the increased use of direct current in high voltage electrical systems. In this context, a significant relevance has been achieved by the thermal methods, used for solid dielectrics. This paper presents a review of this non-destructive measurement system used for the measurement of space charge. The thermal pulse method, the thermal step method, and the laser intensity modulation method are described. For each configuration, the principle of operation, the thicknesses analyzed, and the spatial resolution are described, reporting also the main related applications.
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Neoplasias Cardíacas/diagnóstico , Mixoma/diagnóstico , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Feminino , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/tratamento farmacológico , Neoplasias Cardíacas/patologia , Hospitalização , Humanos , Achados Incidentais , Mixoma/diagnóstico por imagem , Mixoma/tratamento farmacológico , Mixoma/patologia , Doenças Raras , Resultado do Tratamento , UltrassonografiaAssuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Trombose/tratamento farmacológico , Trombose/patologia , Vitamina K/antagonistas & inibidores , Idoso de 80 Anos ou mais , Antitrombinas/administração & dosagem , Dabigatrana/administração & dosagem , Dispneia/diagnóstico , Ecocardiografia/métodos , Humanos , Masculino , Radiografia , Trombose/diagnóstico por imagem , Tomógrafos Computadorizados , Falha de TratamentoRESUMO
PURPOSE: To develop a consensus opinion regarding capturing diagnosis-timing in coded hospital data. METHODS: As part of the World Health Organization International Classification of Diseases-11th Revision initiative, the Quality and Safety Topic Advisory Group is charged with enhancing the capture of quality and patient safety information in morbidity data sets. One such feature is a diagnosis-timing flag. The Group has undertaken a narrative literature review, scanned national experiences focusing on countries currently using timing flags, and held a series of meetings to derive formal recommendations regarding diagnosis-timing reporting. RESULTS: The completeness of diagnosis-timing reporting continues to improve with experience and use; studies indicate that it enhances risk-adjustment and may have a substantial impact on hospital performance estimates, especially for conditions/procedures that involve acutely ill patients. However, studies suggest that its reliability varies, is better for surgical than medical patients (kappa in hip fracture patients of 0.7-1.0 versus kappa in pneumonia of 0.2-0.6) and is dependent on coder training and setting. It may allow simpler and more precise specification of quality indicators. CONCLUSIONS: As the evidence indicates that a diagnosis-timing flag improves the ability of routinely collected, coded hospital data to support outcomes research and the development of quality and safety indicators, the Group recommends that a classification of 'arising after admission' (yes/no), with permitted designations of 'unknown or clinically undetermined', will facilitate coding while providing flexibility when there is uncertainty. Clear coding standards and guidelines with ongoing coder education will be necessary to ensure reliability of the diagnosis-timing flag.
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Diagnóstico , Hospitais/estatística & dados numéricos , Classificação Internacional de Doenças/normas , Segurança do Paciente/normas , Qualidade da Assistência à Saúde/normas , Comitês Consultivos , Coleta de Dados/métodos , Coleta de Dados/normas , Coleta de Dados/estatística & dados numéricos , Mortalidade Hospitalar , Hospitais/normas , Humanos , Segurança do Paciente/estatística & dados numéricos , Melhoria de Qualidade/normas , Melhoria de Qualidade/estatística & dados numéricos , Qualidade da Assistência à Saúde/estatística & dados numéricos , Fatores de TempoRESUMO
The Cystic Fibrosis (CF) Unit of Children's Hospital Bambino Gesù in Rome (Italy) has more than 25 years of experience in diagnosis and treatment of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) related diseases. The CF Unit actively collaborates with the Transplantation Division for the follow-up of patients with CF who undergo lung transplantation, performed in our Unit since 1991. We present the case of a 19 year-old girl with CF, with severe respiratory failure for which it was subjected to two lung transplant. During the follow-up the remote monitoring has allowed the identification of an early episode of pulmonary relapse and graft-versus-host reaction even before the onset of symptoms, allowing an effective intervention and a complete recovery of lung function.