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1.
Artigo em Inglês | MEDLINE | ID: mdl-38871574

RESUMO

BACKGROUND: The COVID-19 pandemic has highlighted the vulnerability of particular patient groups to SARS-CoV-2 infection, including those with cardiovascular diseases, hypertension, and intestinal dysbiosis. COVID-19 affects the gut, suggesting diet and vitamin D3 supplementation may affect disease progression. AIMS: To evaluate levels of Ang II and Ang-(1-7), cytokine profile, and gut microbiota status in patients hospitalized for mild COVID-19 with a history of cardiovascular disease and treated with daily doses of vitamin D3. METHODS: We recruited 50 adult patients. We screened 50 adult patients and accessed pathophysiology study 22, randomized to daily oral doses of 10,000IU vitamin D3 (n=11) or placebo (n=11). Plasma levels of Ang II and Ang-(1-7) were determined by radioimmunoassay, TMA and TMAO were measured by liquid chromatography and interleukins (ILs) 6, 8, 10 and TNF-α by ELISA. RESULTS: The Ang-(1-7)/Ang II ratio, as an indirect measure of ACE2 enzymatic activity, increased in the vitamin D3 group (24±5pg/mL vs. 4.66±2pg/mL, p<0.01). Also, in the vitamin D3-treated, there was a significant decline in inflammatory ILs and an increase in protective markers, such as a substantial reduction in TMAO (5±2µmoles/dL vs. 60±10µmoles/dL, p<0.01). In addition, treated patients experienced less severity of infection, required less intensive care, had fewer days of hospitalization, and a reduced mortality rate. Additionally, improvements in markers of cardiovascular function were seen in the vitamin D3 group, including a tendency for reductions in blood pressure in hypertensive patients. CONCLUSIONS: Vitamin D3 supplementation in patients with COVID-19 and specific conditions is associated with a more favourable prognosis, suggesting therapeutic potential in patients with comorbidities such as cardiovascular disease and gut dysbiosis.

2.
Blood Cancer J ; 14(1): 74, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684670

RESUMO

Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting.


Assuntos
Biomarcadores Tumorais , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Mutação , Mieloma Múltiplo Latente , Humanos , Masculino , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Mieloma Múltiplo Latente/genética , Biomarcadores Tumorais/genética , Pessoa de Meia-Idade , Idoso , Sequenciamento de Nucleotídeos em Larga Escala , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
3.
Semin Hematol ; 60(2): 80-89, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-37147252

RESUMO

The consensus panel 2 (CP2) of the 11th International Workshop on Waldenström's macroglobulinemia (IWWM-11) has reviewed and incorporated current data to update the recommendations for treatment approaches in patients with relapsed or refractory WM (RRWM). The key recommendations from IWWM-11 CP2 include: (1) Chemoimmunotherapy (CIT) and/or a covalent Bruton tyrosine kinase (cBTKi) strategies are important options; their use should reflect the prior upfront strategy and are subject to their availability. (2) In selecting treatment, biological age, co-morbidities and fitness are important; nature of relapse, disease phenotype and WM-related complications, patient preferences and hematopoietic reserve are also critical factors while the composition of the BM disease and mutational status (MYD88, CXCR4, TP53) should also be noted. (3) The trigger for initiating treatment in RRWM should utilize knowledge of patients' prior disease characteristics to avoid unnecessary delays. (4) Risk factors for cBTKi related toxicities (cardiovascular dysfunction, bleeding risk and concurrent medication) should be addressed when choosing cBTKi. Mutational status (MYD88, CXCR4) may influence the cBTKi efficacy, and the role of TP53 disruptions requires further study) in the event of cBTKi failure dose intensity could be up titrated subject to toxicities. Options after BTKi failure include CIT with a non-cross-reactive regimen to one previously used CIT, addition of anti-CD20 antibody to BTKi, switching to a newer cBTKi or non-covalent BTKi, proteasome inhibitors, BCL-2 inhibitors, and new anti-CD20 combinations are additional options. Clinical trial participation should be encouraged for all patients with RRWM.


Assuntos
Antineoplásicos , Macroglobulinemia de Waldenstrom , Humanos , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/genética , Fator 88 de Diferenciação Mieloide/genética , Consenso , Recidiva Local de Neoplasia/induzido quimicamente , Recidiva Local de Neoplasia/tratamento farmacológico , Antineoplásicos/uso terapêutico
4.
Semin Hematol ; 60(2): 107-112, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-37099029

RESUMO

Consensus Panel 5 (CP5) of the 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11; held in October 2022) was tasked with reviewing the current data on the coronavirus disease-2019 (COVID-19) prophylaxis and management in patients with Waldenstrom's Macroglobulinemia (WM). The key recommendations from IWWM-11 CP5 included the following: Booster vaccines for SARS-CoV-2 should be recommended to all patients with WM. Variant-specific booster vaccines, such as the bivalent vaccine for the ancestral Wuhan strain and the Omicron BA.4.5 strain, are important as novel mutants emerge and become dominant in the community. A temporary interruption in Bruton's Tyrosine Kinase-inhibitor (BTKi) or chemoimmunotherapy before vaccination might be considered. Patients under treatment with rituximab or BTK-inhibitors have lower antibody responses against SARS-CoV-2; thus, they should continue to follow preventive measures, including mask wearing and avoiding crowded places. Patients with WM are candidates for preexposure prophylaxis, if available and relevant to the dominant SARS-CoV-2 strains in a specific area. Oral antivirals should be offered to all symptomatic WM patients with mild to moderate COVID-19 regardless of vaccination, disease status or treatment, as soon as possible after the positive test and within 5 days of COVID-19-related symptom onset. Coadministration of ibrutinib or venetoclax with ritonavir should be avoided. In these patients, remdesivir offers an effective alternative. Patients with asymptomatic or oligosymptomatic COVID-19 should not interrupt treatment with a BTK inhibitor. Infection prophylaxis is essential in patients with WM and include general preventive measures, prophylaxis with antivirals and vaccination against common pathogens including SARS-CoV-2, influenza, and S. pneumoniae.


Assuntos
COVID-19 , Macroglobulinemia de Waldenstrom , Humanos , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/prevenção & controle , Macroglobulinemia de Waldenstrom/diagnóstico , Vacinas contra COVID-19 , Consenso , SARS-CoV-2 , Antivirais/uso terapêutico
5.
Semin Hematol ; 60(2): 118-124, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-37099031

RESUMO

Recent advances in the understanding of Waldenström macroglobulinemia (WM) biology have impacted the development of effective novel agents and improved our knowledge of how the genomic background of WM may influence selection of therapy. Consensus Panel 7 (CP7) of the 11th International Workshop on WM was convened to examine the current generation of completed and ongoing clinical trials involving novel agents, consider updated data on WM genomics, and make recommendations on the design and prioritization of future clinical trials. CP7 considers limited duration and novel-novel agent combinations to be the priority for the next generation of clinical trials. Evaluation of MYD88, CXCR4 and TP53 at baseline in the context of clinical trials is crucial. The common chemoimmunotherapy backbones, bendamustine-rituximab (BR) and dexamethasone, rituximab and cyclophosphamide (DRC), may be considered standard-of-care for the frontline comparative studies. Key unanswered questions include the definition of frailty in WM; the importance of attaining a very good partial response or better (≥VGPR), within stipulated time frame, in determining survival outcomes; and the optimal treatment of WM populations with special needs.


Assuntos
Macroglobulinemia de Waldenstrom , Humanos , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/genética , Rituximab/uso terapêutico , Consenso , Ciclofosfamida/uso terapêutico , Cloridrato de Bendamustina/uso terapêutico
6.
Rev Esp Quimioter ; 36(1): 1-25, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36322133

RESUMO

We do not know the precise figure for solid organ tumors diagnosed each year in Spain and it is therefore difficult to calculate whether there has been a decrease in cancer diagnoses as a consequence of the pandemic. Some indirect data suggest that the pandemic has worsened the stage at which some non-hematological neoplasms are diagnosed. Despite the lack of robust evidence, oncology patients seem more likely to have a poor outcome when they contract COVID-19. The antibody response to infection in cancer patients will be fundamentally conditioned by the type of neoplasia present, the treatment received and the time of its administration. In patients with hematological malignancies, the incidence of infection is probably similar or lower than in the general population, due to the better protective measures adopted by the patients and their environment. The severity and mortality of COVID-19 in patients with hematologic malignancies is clearly higher than the general population. Since the immune response to vaccination in hematologic patients is generally worse than in comparable populations, alternative methods of prevention must be established in these patients, as well as actions for earlier diagnosis and treatment. Campaigns for the early diagnosis of malignant neoplasms must be urgently resumed, post-COVID manifestations should be monitored, collaboration with patient associations is indisputable and it is urgent to draw the right conclusions to improve our preparedness to fight against possible future catastrophes.


Assuntos
COVID-19 , Neoplasias Hematológicas , Humanos , Pandemias/prevenção & controle , COVID-19/diagnóstico , Neoplasias Hematológicas/complicações , Espanha/epidemiologia , Vacinação , Teste para COVID-19
7.
ISA Trans ; 133: 345-352, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36116963

RESUMO

This paper is focused on feedback control of postprandial glucose levels for patients with type 1 Diabetes Mellitus. There are two important limitations that make this a challenging problem. First, the slow subcutaneous insulin pharmacokinetics that introduces a significant lag into the control loop. Second, the positivity constraint on the control action, meaning that it is not possible to remove insulin from the body. In this paper, both issues are explicitly considered in the design process using the internal model control framework, to derive a near-optimal feedback controller. Optimality is understood here as minimizing the blood glucose peak after a meal intake and, at the same time, preventing glucose values below a prescribed threshold. It is shown how the proposed controller approaches the optimal closed-loop performance as a limit case. The theoretical results are supported by a numerical example and the feasibility of the overall strategy under uncertainties is illustrated using an extended version UVa/Padova metabolic simulator.


Assuntos
Diabetes Mellitus Tipo 1 , Pâncreas Artificial , Humanos , Glucose , Retroalimentação , Algoritmos , Insulina , Insulina Regular Humana , Simulação por Computador
8.
Clin Transl Oncol ; 24(6): 968-980, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34997475

RESUMO

CAR-T cell therapy represents a therapeutic revolution in the prognosis and treatment of patients with certain types of hematological cancer. However, they also pose new challenges in the healthcare, regulatory and financial fields. The aim of the RET-A project was to undertake a strategic reflection on the management of CAR-T therapies within the Spanish National Health System, to agree on recommendations that will help to better deal with the new context introduced by these cell therapies in the present and in the future. This think tank involved 40 key agents and opinion leaders. The experts identified three great challenges for implementing advanced therapies in Spain: therapeutic individualisation, with a multidisciplinary approach; acceleration of access times, by minimizing bureaucracy; and increase in the number of centers qualified to manage the CAR-T therapies in the NHS. The experts agreed on the ideal criteria for designating those qualified centers. They also agreed on a comprehensive CAR-T care pathway with the timings and roles which would ideally be involved in each part of the process.


Assuntos
Neoplasias Hematológicas , Receptores de Antígenos Quiméricos , Consenso , Humanos , Imunoterapia Adotiva , Espanha
9.
Br J Biomed Sci ; 78(4): 244-247, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34105441

RESUMO

Mixed acute rejection is a clinicopathological entity that is difficult to accurately diagnose, and so may be under-reported. Allografts are lost more often than in either humoral or cellular rejection. The diagnosis requires both histological and immunological studies on renal biopsy and blood specimens from the transplant recipient to provide the required rescue therapy to abolish the allogeneic response against the graft. We present a clinical case report of an active mixed acute rejection driven by a de novo donor-specific complement-binding anti-DQB1*03:01 antibody and intraepithelial CD8 T-cells in a patient with a kidney transplant. The patient was diagnosed, treated, and followed up as per the local institution's procedure with a full recovery of graft function. Our case emphasises the challenge of a mixed acute rejection and supports the need to improve the post-transplant outcome of recipients and their grafts.


Assuntos
Rejeição de Enxerto , Isoanticorpos , Linfócitos T CD8-Positivos , Antígenos HLA , Humanos , Rim
10.
ESMO Open ; 6(3): 100157, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34015642

RESUMO

BACKGROUND: Studies evaluating the effects of the COVID-19 pandemic on public healthcare systems are limited, particularly in cancer management. As no such studies have been carried out in Spain, our objective is to describe and quantify the impact of the COVID-19 pandemic on cancer patients in Spanish hospitals during the first wave of the pandemic. MATERIALS AND METHODS: This retrospective, multicenter, nationwide study collected information from hospital departments treating oncology patients. An electronic questionnaire comparing outcomes and management of oncohematological patients for the March-June 2019 and March-June 2020 periods was used. RESULTS: Information from 78 departments (36 tertiary hospitals) was analyzed. Forty-four departments implemented adapted protocols during March 2020. Most of these (n = 38/44; 86.4%) carried out COVID-19 triage, while 26 of 44 (59.1%) carried out onsite polymerase chain reaction tests for clinically suspected cases. A shift from in-person to telephone visits was observed in 43 of 44 (97.7%) departments. Comparing the March-June 2019 and March-June 2020 periods, the number of new patients decreased by 20.8% (from 160.2 to 126.4). Decreases were also seen in the mean number of total (2858.2 versus 1686.1) and cancer (465.5 versus 367.2) biopsies, as well as the mean number of bone marrow biopsies (30.5 versus 18.6). Concerning the number of patients visiting specific cancer care departments, a decrease from 2019 to 2020 was seen for mean number of chemotherapy treatments (712.7 versus 643.8) and radiation therapy (2169.9 versus 2139.9). Finally, a reduction from 2019 to 2020 of 12.9% (from 8.6 to 7.4) in the mean number of patients included in clinical trials was noted. CONCLUSIONS: This study provides the first comprehensive data concerning the impact of COVID-19 on cancer care in Spain. The pandemic caused a 20.8% decrease in newly diagnosed patients, which may impact future outcomes. Measures must be taken to ensure cancer management receives priority in times of healthcare emergencies.


Assuntos
COVID-19 , Neoplasias , Humanos , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Espanha
11.
J Mater Chem B ; 9(20): 4178-4189, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-33989370

RESUMO

Parkinson's disease (PD) is a progressive neurodegenerative disease, the 2nd most common after Alzheimer's disease, the main effect of which is the loss of dopaminergic neurons. Levodopa or l-Dopa is an amino acid used in the treatment of PD that acts as the immediate precursor to dopamine. However, over time the efficacy of the medication gradually decreases requiring modified delivery methods. One of the major challenges for the medication to work is to achieve a gradual continuous supply of l-Dopa to the brain to minimise symptoms. Herein, mesoporous silica nanoparticles (MSNs) were engineered through the concept of drug-structure-directing agents (DSDAs) with inherent therapeutic activity. The DSDA used was l-Dopa drug modified by amidation with fatty acids to build anionic surfactants that were able to form micelles as templates for the assembly of inorganic precursors to form the silica framework. This templating route produced MSNs with tunable sizes ranging from 100 nm to 1 µm and with different shapes: spherical, with either solid structures with radial mesopores and porous shells, or hollow-shells with inside large void cavities; and elongated, characterized by long hollows covered by mesoporous shells. The concept of using DSDAs to synthesize drug nanocarriers can be used to avoid the surfactant removal and subsequent drug loading steps involved in the synthesis of conventional MSNs. We hypothesized that the l-Dopa released from MSN materials is mediated by the size and solubility of the DSDAs, and the surface chemical interactions between the DSDAs and MSN hosts. Different pHs (acidic and neutral) simulating gastrointestinal tract conditions were tested, and the results showed hardly any release for gastric conditions at pH 1.2, avoiding the premature release in the stomach typical of conventional MSNs, while for intestinal conditions of pH 7.4, the release of l-Dopa occurred in a continuous and sustained manner, which is well suited to the drug's application and delivery route, and matches well with achieving a sustained l-Dopa delivery to relief symptoms. This could open up new uses for MSNs synthesized by this approach to treat PD.


Assuntos
Antiparkinsonianos/uso terapêutico , Levodopa/uso terapêutico , Nanopartículas/química , Doença de Parkinson/tratamento farmacológico , Dióxido de Silício/química , Antiparkinsonianos/síntese química , Antiparkinsonianos/química , Liberação Controlada de Fármacos , Humanos , Levodopa/síntese química , Levodopa/química , Tamanho da Partícula , Porosidade , Propriedades de Superfície
12.
Data Brief ; 33: 106488, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33241096

RESUMO

Cement based materials may contain varying levels of radionuclides, mainly 226Ra (from the 238U series), 232Th and 40K, which are used to determine the Activity Concentration Index ("ACI"). According to the European directive Euratom 2013/59 in these materials, the "ACI" must be < 1 to be suitable for their use in construction. In this paper, data on the activity concentration of natural radionuclides in cement-based materials (i.e. cements, additions, pigments and aggregates) as well as their chemical composition are presented. Radioactivity measurements have been determined by using gamma spectroscopy the chemical compositions have been determined by X-Ray Fluorescence. Data for cements measured shown that white cements present a lower concentration of activity than conventional CEM I. In addition, the CAC (Calcium aluminate cements) present high activity concentration in the 232Th series. Regarding additions, FA (Fly Ash) are those that present the highest concentration of activity in the 238U and 232Th series, while olive biomass ashes are those supplementary cementitious materials that show the highest concentration of activity for 40K. Some pigments used in mortar and concrete technology were also characterized. Granitic and volcanic rocks, potentially used as aggregates present much higher activity concentration than the siliceous aggregate.

13.
J Med Vasc ; 45(6): 316-325, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33248534

RESUMO

OBJECTIVE: To document the efficacy of a combined therapeutic strategy in achieving rapid wound healing in patients with long-standing ulcers. MATERIALS AND METHODS: Outpatients with hard-to-heal venous leg ulcers were included in an interventional, prospective, single-arm, mono-centre study and treated with autologous punch grafting, TLC-NOSF dressing and multi-type compression therapy. The primary outcome was the percentage of healed wounds by week 12. Secondary outcomes included time-to-reach wound closure, wound area reduction, treatment acceptability and safety. RESULTS: From November 2018 to October 2019, 42 patients with 51 ulcers were included (23 males, 70.6±40.8 years old, with multiple comorbidities). Despite poor wound healing prognosis at baseline (47% of recurrent ulcers, with a mean duration of 15 months and a mean area of 12.6cm2), wound healing was achieved in 47 ulcers (92%) after a mean period of treatment of 25±13 days. A relative wound area reduction>75% was also reached in three additional ulcers by the last evaluation visit. No adverse event related to the procedure was reported throughout the study period. The associated treatment were very well tolerated and accepted by the patients. CONCLUSIONS: The evaluated procedure induced fast re-epithelisation of the treated ulcers. Based on our experience, this simple and successful reparative strategy may be considered as an interesting option in the treatment of venous leg ulcers of poor prognosis.


Assuntos
Bandagens , Bandagens Compressivas , Transplante de Pele , Úlcera Varicosa/terapia , Técnicas de Fechamento de Ferimentos , Cicatrização , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Recidiva , Fatores de Tempo , Transplante Autólogo , Resultado do Tratamento , Úlcera Varicosa/diagnóstico , Úlcera Varicosa/fisiopatologia
14.
Actas Dermosifiliogr (Engl Ed) ; 111(1): 26-40, 2020 Jan 02.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32197684

RESUMO

Hand eczema is a common condition associated with significantly impaired quality of life and high social and occupational costs. Managing hand eczema is particularly challenging for primary care and occupational health physicians as the condition has varying causes and both disease progression and response to treatment are difficult to predict. Early diagnosis and appropriate protective measures are essential to prevent progression to chronic eczema, which is much more difficult to treat. Appropriate referral to a specialist and opportune evaluation of the need for sick leave are crucial to the good management of these patients. These guidelines cover the diagnosis, prevention, and treatment of chronic hand eczema and highlight the role that primary care and occupational health physicians can play in the early management of this disease.


Assuntos
Eczema/diagnóstico , Eczema/terapia , Dermatoses da Mão/diagnóstico , Dermatoses da Mão/terapia , Algoritmos , Árvores de Decisões , Eczema/prevenção & controle , Dermatoses da Mão/prevenção & controle , Humanos
15.
Clin Transl Oncol ; 22(8): 1418-1422, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31863353

RESUMO

PURPOSE: The aim of the current survey was to describe the functioning of cardio-oncology (C-O) units in Spain. METHODS: All members of the Spanish Society of Cardiology pertaining to scientific communities related to C-O received questionnaires on the existence of specific programs at their institutions. A second, more extensive questionnaire was sent to the centers which reported C-O organization. RESULTS: We identified 56 centers with C-O programs of which 32 (62.5%) replied to the extended questionnaire. 28% of all centers reported having a multidisciplinary unit involving specialists in several areas. More than 80% of the centers developed surveillance protocols locally adapted which included advanced echocardiographic techniques (68%) or troponin (82%). CONCLUSIONS: The number of institutions with C-O programs is still limited but higher than reported in a survey in 2017. Development of multidisciplinary units of C-O should be promoted to improve the cardiovascular health of cancer patients.


Assuntos
Institutos de Câncer/organização & administração , Serviço Hospitalar de Cardiologia/organização & administração , Pesquisas sobre Atenção à Saúde/estatística & dados numéricos , Oncologia/organização & administração , Neoplasias/terapia , Institutos de Câncer/estatística & dados numéricos , Serviço Hospitalar de Cardiologia/estatística & dados numéricos , Humanos , Oncologia/estatística & dados numéricos , Desenvolvimento de Programas , Espanha
17.
Hipertens Riesgo Vasc ; 36(4): 184-192, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-30926254

RESUMO

INTRODUCTION AND OBJECTIVES: The Systematic Coronary Risk Evaluation (SCORE) is the most extended index in Europe for overall cardiovascular risk assessment. This study aims to validate the calculated risk with the observed 10-year cardiovascular mortality in a population cohort aged 40 to 75 years. METHODS: In 2014 the SCORE and the SCORE OP (for older people) were calculated in a population aged 40 to 64 years-old and 65 to 75 years-old, respectively. In 2014 the 10-year mortality was estimated with the Kaplan-Meier estimator and survival model. Sensitivity, specificity, predictive values, risk ratio of a SCORE value≥5%, and the area under the curve (C statistic) were calculated. RESULTS: Cardiovascular mortality estimated by SCORE was 3 times higher than the observed mortality. The sensitivity of a SCORE≥5% was 20% in women and 28.6% in those less than 65 years old. Predictive positive values were also low, particularly in women with 0.6%. Neither women nor those aged less than 65 years had a significant C statistic. CONCLUSIONS: The SCORE index does not suitably reflect the cardiovascular mortality pattern in Castilla y León. The prediction models for morbidity and mortality need to be periodically updated in order to adjust the prevention and treatment protocols. The SCORE OP has better validity parameters than the SCORE calculated below that age.


Assuntos
Doenças Cardiovasculares/diagnóstico , Medição de Risco , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espanha
18.
Ann Oncol ; 30(4): 612-620, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30657848

RESUMO

BACKGROUND: In this work, we assessed the efficacy and safety of brentuximab vedotin (BV) plus ESHAP (BRESHAP) as second-line therapy for Relapsed/Refractory Hodgkin lymphoma (RRHL) to improve the results before autologous stem-cell transplantation (ASCT). PATIENTS AND METHODS: This was a multicenter, open-label, phase I-II trial of patients with RRHL after first-line chemotherapy. Treatment had three 21-day cycles of etoposide, solumedrol, high-dose AraC, and cisplatin. BV was administered at three dose levels (0.9, 1.2, and 1.8 mg/kg) intravenous on day ‒1 to 3 + 3 cohorts of patients. Final BV dose was 1.8 mg/kg. Responding patients proceeded to ASCT, followed by three BV courses (1.8 mg/kg, every 21 days). Main end points for evaluation were maximum tolerable dose and overall and complete response (CR) before ASCT. RESULTS: A total of 66 patients were recruited (median age 36 years; range 18-66): 40 were primary refractory, 16 early relapse and 10 late relapse. There were 39 severe adverse events were reported in 22 patients, most frequently fever (n = 25, 35% neutropenic), including 3 deaths. Grade 3-4 hematological toxicity presented in 28 cases: neutropenia (n = 21), thrombocytopenia (n = 14), and anemia (n = 7). Grade ≥3-4 extrahematological adverse events (≥5%) were non-neutropenic fever (n = 13) and hypomagnesaemia (n = 3). Sixty-four patients underwent stem-cell mobilization; all collected >2×10e6/kg CD34+ cells (median 5.75; range 2.12-33.4). Overall response before transplant was 91% (CI 84% to 98%), including 70% (CRs 95% CI 59% to 81%). 60 patients were transplanted with no failure engraftments. Post-transplant response was CR in 49 patients (82% CI 73% to 91%) and partial responses in six (10% CI 5% to 15%). After a mean follow-up of 27 months, the 30-month time to treatment to failure was 74% (95% CI 68% to 80%), progression-free survival 71% (95% CI 65% to 77%), and overall survival 91% (CI 84% to 98%). CONCLUSION: BRESHAP looks a safe and effective pre-transplant induction regimen, does not jeopardize transplant and allows long-term remissions and survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Brentuximab Vedotin/administração & dosagem , Neutropenia Febril Induzida por Quimioterapia/epidemiologia , Doença de Hodgkin/terapia , Recidiva Local de Neoplasia/terapia , Terapia de Salvação/métodos , Administração Intravenosa , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Brentuximab Vedotin/efeitos adversos , Neutropenia Febril Induzida por Quimioterapia/etiologia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Intervalo Livre de Progressão , Terapia de Salvação/efeitos adversos , Transplante Autólogo , Adulto Jovem
19.
Med Intensiva (Engl Ed) ; 43(6): 337-345, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29789184

RESUMO

BACKGROUND: Strategies for cardio-protection are essential in coronary artery bypass graft surgery. The authors explored the relationship between cardioplegia volume, left ventricular mass index and ischemia time by means of the infused cardioplegia index and its relationship with post-operative low cardiac output syndrome. DESIGN: All patients undergoing coronary artery bypass graft surgery between January 2013 and December 2015 were included. Low cardiac output syndrome was defined according to criteria of the SEMICYUC's consensus document. The perioperative factors associated with low cardiac output syndrome were estimated, and using a ROC curve, the optimum cut-off point for the infused cardioplegia index to predict the absence of low cardiac output syndrome was calculated. RESULTS: Of 360 patients included, 116 (32%) developed low cardiac output syndrome. The independent risk predictors were: New York Heart Association Functional Classification (OR 1.8 [95% CI=1.18-2.55]), left ventricle ejection fraction (OR 0.95 (95% CI=0.93-0.98]), ICI (OR 0.99 [95% CI=0.991-0.996]) and retrograde cardioplegia (OR 1.2 [95% CI=1.03-1.50]). The infused cardioplegia index showed an area under the ROC curve of 0.77 (0.70-0.83; P<.001) for the absence of postoperative low cardiac output syndrome using the optimum cut-off point of 23.6ml·min-1(100g/m2 of LV)-1. CONCLUSIONS: The infused cardioplegia index presents an inverse relationship with the development of post-operative low cardiac output syndrome. This index could form part of new strategies aimed at optimising cardio-protection. The total volume of intermittent cardioplegia, especially that of maintenance, should probably be individualised, adjusting for ischemia time and left ventricle mass index.


Assuntos
Baixo Débito Cardíaco/epidemiologia , Soluções Cardioplégicas/administração & dosagem , Ponte de Artéria Coronária , Complicações Pós-Operatórias/epidemiologia , Idoso , Baixo Débito Cardíaco/prevenção & controle , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos
20.
Hipertens Riesgo Vasc ; 36(3): 122-129, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-30244994

RESUMO

OBJECTIVES: To describe the characteristics of hypertensive urgencies at the emergency department, as well as the variables associated with early re-admission (<7 days) and re-admission at one month (<30 days). METHODS: We conducted a descriptive, retrospective study of all patients who were admitted to the emergency department of a third level hospital during 2013. Subsequently, a case-control analysis was performed to analyze the group of patients with readmission. RESULTS: A total of 398 hypertensive urgencies were collected (32.4% men, mean age 67.75 years), which led to an incidence of 3.28/1000 visits. Eighty point nine percent had a previous history of hypertension, and the mean Charlson Index was 2.23. Headache was the most frequent symptom (49.1%), followed by dizziness/instability (29.5%) and nausea/vomiting (17.1%). Eighty point seven percent of the patients were prescribed pharmacological treatment. The rates of cardiovascular events or mortality at one month were low (2.26% and 0.25% respectively). Despite this, 7.53% and 11.31% of patients were readmitted in under 7 days or 30 days, respectively. The variables associated with readmission in the multivariate analysis were elevated systolic blood pressure in the first determination, previous hypertension and the presence of palpitations. CONCLUSIONS: Hypertensive emergencies are high-incidence conditions in the Emergency Department. In our study, patients with a prior diagnosis of hypertension and elevated systolic blood pressure at the first determination had a higher risk of re-entry and would be candidates for closer follow-up on discharge.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Hipertensão/terapia , Readmissão do Paciente/estatística & dados numéricos , Idoso , Estudos de Casos e Controles , Emergências , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Incidência , Masculino , Prognóstico , Estudos Retrospectivos
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