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INTRODUCTION: With the increasing prevalence of atrial fibrillation (AF), it entails expanding oral anticoagulants (OACs) use, carrying a higher risk of associated hemorrhagic events, including intracranial hemorrhage (ICH). Despite advances in OACs development with a better safety profile and reversal agent for these anticoagulants, there is still no consensus on the optimal management of patients with OACs-associated ICH. AREAS COVERED: In this review, the authors have carried out an exhaustive search on the advances in recent years. The authors provide an update on the management of ICH in anticoagulated patients, as well as an update on the latest evidence on anticoagulation resumption, recent therapeutic strategies, and investigational drugs that could play a role in the future. EXPERT OPINION: Following an ICH event in an anticoagulated patient, a comprehensive clinical evaluation is imperative. Anticoagulation should be promptly withdrawn and reversed. Once the patient is stabilized, a reintroduction of anticoagulation should be considered, typically within a timeframe of 4-8 weeks, if feasible. If re-anticoagulation is not possible, alternative options such as Left Atrial Appendage Occlusion are available.
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Anticoagulantes , Fibrilación Atrial , Hemorragias Intracraneales , Humanos , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Hemorragias Intracraneales/inducido químicamente , Administración OralRESUMEN
Purpose: The aim of this study was to translate, culturally adapt, and evaluate the psychometric properties of the Spanish Long-Term Quality of Life (LTQL) questionnaire. Methods: The LTQL was initially translated into Spanish and cross-culturally adapted based on established guidelines. The Spanish LTQL was administered to patients with breast cancer who had completed their initial treatment 5 years earlier, along with other self-report measures: Quality of Life in Adult Cancer Survivors (QLACS), Hospital Anxiety and Depression Scale (HADS) and EORT-QLQ-BR23. Reliability was evaluated using internal consistency and test-retest. Convergent and known-groups validity were examined. Structural validity as determined by confirmatory factor analysis (CFA) and Rasch analyses was used to assess the unidimensionality and item-functioning of the LTQL domains. Results: Cronbach's alpha were above 0.7 in all domains. Test-retest coefficients were between 0.72 to 0.96 for LTQL domains. LTQL total score was correlated with others total scores of other measures: QLACS (r=-0.39), HADS depression (r=-0.57), HADS anxiety (-0.45) and EORTC-QLQ-BR23 (r=-0.50). CFA provided satisfactory fit indices, with RMSEA value of 0.077 and TLI and CFI values of 0.901 and 0.909, respectively. All factor loadings were higher than 0.40 and statistically significant (P<0.001). Rasch analysis showed that Somatic Concerns domain had 4 misfitting items, and Philosophical/Spiritual View of Life and social Support domains only 1 misfit item. However, unidimensionality was supported for the four domains. Conclusion: The findings support the validity and reliability of the Spanish version of LTQL questionnaire to be used in long-term cancer female survivors.
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BACKGROUND: During the first COVID-19 pandemic wave, COVID-19-associated pulmonary aspergillosis (CAPA) has been reported in up to 11-28% of critically ill COVID-19 patients and associated with increased mortality. As new SARS-CoV-2 variants emerged, the characteristics of critically ill COVID-19 patients have evolved, particularly in the era of Omicron. The purpose of this study is to investigate the characteristics of CAPA in the era of new variants. METHODS: This is a prospective multicenter observational cohort study conducted in France in 36 participating intensive care units (ICU), between December 7th, 2021 and April 26th 2023. Diagnosis criteria of CAPA relied on European Confederation of Medical Mycology (ECMM)/International Society for Human & Animal Mycology (ISHAM) consensus criteria. RESULTS: 566 patients were included over the study period. The prevalence of CAPA was 5.1% [95% CI 3.4-7.3], and rose to 9.1% among patients who required invasive mechanical ventilation (IMV). Univariable analysis showed that CAPA patients were more frequently immunosuppressed and required more frequently IMV support, vasopressors and renal replacement therapy during ICU stay than non-CAPA patients. SAPS II score at ICU admission, immunosuppression, and a SARS-CoV-2 Delta variant were independently associated with CAPA in multivariable logistic regression analysis. Although CAPA was not significantly associated with day-28 mortality, patients with CAPA experienced a longer duration of mechanical ventilation and ICU stay. CONCLUSION: This study contributes valuable insights into the prevalence, characteristics, and outcomes of CAPA in the era of Delta and Omicron variants. We report a lower prevalence of CAPA (5.1%) among critically-ill COVID-19 patients than previously reported, mainly affecting intubated-patients. Duration of mechanical ventilation and ICU stay were significantly longer in CAPA patients.
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BACKGROUND: Despite current broad natural and vaccine-induced protection, a substantial number of patients infected with emerging SARS-CoV-2 variants (e.g., BF.7 and BQ.1.1) still experience severe COVID-19. Real-life studies investigating the impact of these variants on clinical outcomes of severe cases are currently not available. We performed a prospective multicenter observational cohort study. Adult patients with acute respiratory failure admitted between December 7, 2021 and December 15, 2022, in one of the 20 participating intensive care units (17 from the Greater Paris area and 3 from the North of France) were eligible for inclusion if they had SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction (RT-PCR). Full-length SARS-CoV-2 genomes from all included patients were sequenced by means of next-generation sequencing. The primary endpoint of the study was day-28 mortality. RESULTS: The study included 158 patients infected with three groups of Omicron sublineages, including (i) BA.2 variants and their early sublineages referred as "BA.2" (n = 50), (ii) early BA.4 and BA.5 sublineages (including BA.5.1 and BA.5.2, n = 61) referred as "BA.4/BA.5", and (iii) recent emerging BA.5 sublineages (including BQ.1, BQ.1.1, BF.7, BE.1 and CE.1, n = 47) referred as "BQ.1.1". The clinical phenotype of BQ1.1-infected patients compared to earlier BA.2 and BA.4/BA.5 sublineages, showed more frequent obesity and less frequent immunosuppression. There was no significant difference between Omicron sublineage groups regarding the severity of the disease at ICU admission, need for organ failure support during ICU stay, nor day 28 mortality (21.7%, n = 10/47 in BQ.1.1 group vs 26.7%, n = 16/61 in BA.4/BA.5 vs 22.0%, n = 11/50 in BA.2, p = 0.791). No significant relationship was found between any SARS-CoV-2 substitution and/or deletion on the one hand and survival on the other hand over hospital follow-up. CONCLUSIONS: Critically-ill patients with Omicron BQ.1.1 infection showed a different clinical phenotype than other patients infected with earlier Omicron sublineage but no day-28 mortality difference.
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INTRODUCTION: In spite of the changes for the treatment of glioblastoma since 2005, we have not seen differences between long-survival patients of more than 10 years showing a value minor than 1%. MATERIAL AND METHOD: We realize a systematic analysis and identify important factors for long survivor patients. We also show an own case with more of 20 years of survival. We make a new pathological study of the old paraffin block of this patient. RESULTS: The most important variable associated with long-survival between all multivariant studies is the age. When we try to find genetic and molecular alterations in glioblastoma associated with prolongated survival, the MGMT promoter methylation play the most important role. We find a correct diagnosis in the current analysis of our patient's sample with very long survival. CONCLUSIONS: Multiple variables are found that affect long survival of glioblastoma series but analyzed studies are very heterogeneous and it is very difficult comparation between them. Most articles we review are obtained from databases of different countries with hundreds of patients. It would be very interesting to promote the use of a single database in Spain that allows us to study these long-term glioblastoma survivors.
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Neoplasias Encefálicas , Glioblastoma , Neoplasias Encefálicas/patología , Metilación de ADN , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Glioblastoma/terapia , Humanos , Proteínas Supresoras de TumorRESUMEN
Infection with SARS-CoV-2 variant Omicron is considered to be less severe than infection with variant Delta, with rarer occurrence of severe disease requiring intensive care. Little information is available on comorbid factors, clinical conditions and specific viral mutational patterns associated with the severity of variant Omicron infection. In this multicenter prospective cohort study, patients consecutively admitted for severe COVID-19 in 20 intensive care units in France between December 7th 2021 and May 1st 2022 were included. Among 259 patients, we show that the clinical phenotype of patients infected with variant Omicron (n = 148) is different from that in those infected with variant Delta (n = 111). We observe no significant relationship between Delta and Omicron variant lineages/sublineages and 28-day mortality (adjusted odds ratio [95% confidence interval] = 0.68 [0.35-1.32]; p = 0.253). Among Omicron-infected patients, 43.2% are immunocompromised, most of whom have received two doses of vaccine or more (85.9%) but display a poor humoral response to vaccination. The mortality rate of immunocompromised patients infected with variant Omicron is significantly higher than that of non-immunocompromised patients (46.9% vs 26.2%; p = 0.009). In patients infected with variant Omicron, there is no association between specific sublineages (BA.1/BA.1.1 (n = 109) and BA.2 (n = 21)) or any viral genome polymorphisms/mutational profile and 28-day mortality.
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COVID-19 , SARS-CoV-2 , Enfermedad Crítica , Humanos , Fenotipo , Estudios Prospectivos , SARS-CoV-2/genéticaRESUMEN
Background: Within the wide variety of clinical skills distinctive of the internist the diagnostic approach of abdominal pain is paramount in everyday clinical practice. It is well known that no physician can diagnose what they don't know: classically considered as one of the ''great simulators'', intestinal endometriosis is a rare yet potentially fatal cause of abdominal pain if misdiagnosed, thus requiring a comprehensive medical evaluation. Case report: We present the case of a 33-year-old woman evaluated for a bowel obstruction, in the first instance associated with a probable abdominal tumor, subsequently concluding the definitive diagnosis of intestinal endometriosis. Conclusions: Although endometriosis is a frequent pathology, the location and clinical presentation presented in this case is not. However, the lack of information on this, like any other pathology, can delay the diagnosis or carry the risk of offering inappropriate treatments for an incorrect diagnosis. This is the importance of its knowledge and dissemination among first-contact doctors as well as clinical and surgical specialists.
Introducción: Dentro del gran abanico de competencias características del médico clínico se encuentra el abordaje diagnóstico del síndrome doloroso abdominal. Es bien sabido que el médico no diagnostica lo que no conoce. Considerada como una gran simuladora en la patología abdominal, la endometriosis intestinal es una causa de dolor abdominal poco frecuente, pero potencialmente mortal, siendo necesario un abordaje diagnóstico detallado. Caso clínico: Presentamos el caso de una mujer de 33 años evaluada por un cuadro de obstrucción intestinal, en primera instancia asociada a un probable tumor abdominal, concluyendo posteriormente el diagnóstico definitivo de endometriosis intestinal. Conclusiones: Si bien la endometriosis es una patología frecuente, la localización y la presentación clínica de este caso no lo son. Sin embargo, la falta de información de esta, al igual que de cualquier otra patología, puede retrasar el diagnóstico o conllevar el riesgo de ofrecer tratamientos no adecuados por un diagnóstico incorrecto. He aquí la importancia de su conocimiento y difusión entre médicos de primer contacto, así como entre especialistas clínicos y quirúrgicos.
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Dolor Abdominal/etiología , Endometriosis , Obstrucción Intestinal/etiología , Adulto , Diagnóstico Diferencial , Endometriosis/diagnóstico , Femenino , HumanosRESUMEN
Considering that infrared thermography is presented as a diagnostic technique for non-invasive, non-ionizing, fast and easy to use imaging and Emery-Dreifuss muscular dystrophy is a clinical condition that seems to be related to changes in the emission of infrared radiation at the skin level due to its neurodegenerative character, we have conducted an investigation by infrared thermography and the use of functional strength tests in the lower limbs in a family of 4 affected members of Emery-Dreifuss muscular dystrophy to try to establish a relationship between the evolution of the disease and the emission of infrared radiation in this pathology at the lower limb level and provide a more general view of this disease for a better evaluation and monitoring of the disease.
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Distrofia Muscular de Emery-Dreifuss , Humanos , Rayos Infrarrojos , Fuerza Muscular , PielRESUMEN
There are few trials published on treatment in elderly women with low-risk breast cancer. Although the clinical behavior is like younger patients, there is a tendency to undertreat them, which may lead to an increase in the risk of local relapses and decrease their survival. The local recurrences omitting adjuvant treatment (tamoxifen or radiotherapy) after breast conserving surgery (BCS) even in low-risk patients is high, reaching up 20%, which is unacceptable. Although tamoxifen and radiotherapy seem to have a similar effect in reducing local recurrence with equal overall survival, the combination of both achieves the maximum benefit with local relapses of less than 2%. In recent years two studies have been published and were designed specifically for elderly patients. The CALGB 9343 and the PRIME II trials recommend omitting radiotherapy in patients with low-risk tumors treated with BCS and tamoxifen based on a similar survival, but with an increase in local relapses when radiotherapy is omitted, 10% at 10 years vs. 2%. There is no basis to ensure that a treatment with tamoxifen has less toxicity in this group of patients who are usually poly-treated, and it seems that treatment compliance is much lower than expected. The decrease in the number of sessions in external radiotherapy with hypofractionation and accelerate partial breast irradiation, especially intraoperative radiotherapy (IORT) with a single session, makes this recommendation very controversial. Elderly patients may benefit from radiation therapy after BCS.
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Gossypol is a natural disesquiterpene that blocks the activity of the mammalian facilitative hexose transporter GLUT1. In human HL-60 cells, which express GLUT1, Chinese hamster ovary cells overexpressing GLUT1, and human erythrocytes, gossypol inhibited hexose transport in a concentration-dependent fashion, indicating that blocking of GLUT1 activity is independent of cellular context. With the exception of red blood cells, the inhibition of cellular transport was instantaneous. Gossypol effect was specific for the GLUT1 transporter since it did not alter the uptake of nicotinamide by human erythrocytes. Gossypol affects the glucose-displaceable binding of cytochalasin B to GLUT1 in human erythrocyte ghost in a mixed noncompetitive way, with a K(i) value of 20 microM. Likewise, GLUT1 fluorescence was quenched approximately 80% by gossypol, while Stern-Volmer plots for quenching by iodide displayed increased slopes by gossypol addition. These effects on protein fluorescence were saturable and unaffected by the presence of D-glucose. Gossypol did not alter the affinity of D-glucose for the external substrate site on GLUT1. Kinetic analysis of transport revealed that gossypol behaves as a noncompetitive inhibitor of zero-trans (substrate outside but not inside) transport, but it acts as a competitive inhibitor of equilibrium-exchange (substrate inside and outside) transport, which is consistent with interaction at the endofacial surface, but not at the exofacial surface of the transporter. Thus, gossypol behaves as a quasi-competitive inhibitor of GLUT1 transport activity by binding to a site accessible through the internal face of the transporter, but it does not, in fact, compete with cytochalasin B binding. Our observations suggest that some effects of gossypol on cellular physiology may be related to its ability to disrupt the normal hexose flux through GLUT1, a transporter expressed in almost every kind of mammalian cell and responsible for the basal uptake of glucose.
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Eritrocitos/efectos de los fármacos , Transportador de Glucosa de Tipo 1/antagonistas & inhibidores , Glucosa/metabolismo , Gosipol/farmacología , 3-O-Metilglucosa/metabolismo , Animales , Antígenos CD/genética , Antígenos CD/metabolismo , Sitios de Unión , Unión Competitiva , Células CHO , Cricetinae , Cricetulus , Citocalasina B/metabolismo , Desoxiglucosa/metabolismo , Relación Dosis-Respuesta a Droga , Eritrocitos/metabolismo , Transportador de Glucosa de Tipo 1/genética , Transportador de Glucosa de Tipo 1/metabolismo , Gosipol/metabolismo , Células HL-60 , Humanos , Cinética , Modelos Biológicos , Niacinamida/metabolismo , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Espectrometría de Fluorescencia , TransfecciónRESUMEN
'In the original HTML version of this Article, ref.12 was incorrectly cited in the first sentence of the first paragraph of the Introduction. The correct citation is ref. 2. This has now been corrected in the HTML version of the Article; the PDF version was correct at the time of publication.'
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The Southern Ocean is a pivotal component of the global climate system yet it is poorly represented in climate models, with significant biases in upper-ocean temperatures, clouds and winds. Combining Atmospheric and Coupled Model Inter-comparison Project (AMIP5/CMIP5) simulations, with observations and equilibrium heat budget theory, we show that across the CMIP5 ensemble variations in sea surface temperature biases in the 40-60°S Southern Ocean are primarily caused by AMIP5 atmospheric model net surface flux bias variations, linked to cloud-related short-wave errors. Equilibration of the biases involves local coupled sea surface temperature bias feedbacks onto the surface heat flux components. In combination with wind feedbacks, these biases adversely modify upper-ocean thermal structure. Most AMIP5 atmospheric models that exhibit small net heat flux biases appear to achieve this through compensating errors. We demonstrate that targeted developments to cloud-related parameterisations provide a route to better represent the Southern Ocean in climate models and projections.
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COVID-19 , Neoplasias , Oncología por Radiación , Humanos , Neoplasias/radioterapia , SARS-CoV-2 , EspañaRESUMEN
Visual motion provides useful information to understand the dynamics of a scene to allow intelligent systems interact with their environment. Motion computation is usually restricted by real time requirements that need the design and implementation of specific hardware architectures. In this paper, the design of hardware architecture for a bio-inspired neural model for motion estimation is presented. The motion estimation is based on a strongly localized bio-inspired connectionist model with a particular adaptation of spatio-temporal Gabor-like filtering. The architecture is constituted by three main modules that perform spatial, temporal, and excitatory-inhibitory connectionist processing. The biomimetic architecture is modeled, simulated and validated in VHDL. The synthesis results on a Field Programmable Gate Array (FPGA) device show the potential achievement of real-time performance at an affordable silicon area.
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Modelos Neurológicos , Percepción de Movimiento/fisiología , Percepción Visual/fisiología , Vías Nerviosas/fisiología , Percepción Espacial/fisiología , Sinapsis/fisiología , Corteza Visual/fisiologíaRESUMEN
The use of recombinant human erythropoietin (r-HuEPO) in cancer patients improves hemoglobin levels and quality of life. This fact, already well known, made oncologists expect a positive outcome in radio and chemotherapy results, as well as in survival. However, new clinical trials show a preliminary evidence of impaired, instead of improved, survival when these agents are prescribed. Erythropoietin (EPO) is becoming a more complex hormone than it was expected. Its non-erythropoietic effects include, among others, angiogenesis and proliferation of certain types of cancer cells. In this work, we review erythropoietin as a natural hormone, as well as the different types of r-HuEPO, focusing on the confusing situation with regard to their use in oncology. We conclude that extreme care must be taken when EPO is prescribed to cancer patients, and we suggest to limit its use to symptomatic anemia, just to achieve moderate hemoglobin levels.
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Anemia/etiología , Eritropoyetina/fisiología , Eritropoyetina/uso terapéutico , Neoplasias/sangre , Anemia/tratamiento farmacológico , Hemoglobinas/metabolismo , Humanos , Neoplasias/complicaciones , Neoplasias/terapia , Proteínas RecombinantesRESUMEN
Introducción: A pesar de las modificaciones introducidas en el tratamiento de los glioblastomas a partir del 2005, los pacientes supervivientes de más de 10 años se han mantenido constantes, siendo dicha cifra muy pobre e inferior al 1% en la mayoría de los estudios.Material y métodos: Se realiza un análisis sistemático de la literatura identificando los factores que pueden influir en los pacientes de larga supervivencia. Se identifica un caso en nuestro medio de más de 20 años de supervivencia realizándose un análisis actual del bloque de parafina que se conservaba del paciente.Resultados: La variable que más se asocia a la larga supervivencia en todos los análisis multivariantes es la edad, aunque, cuando se analiza las características genéticas y moleculares de los tumores, parecen existir otras variables como la metilación del promotor MGMT que juegan un papel muy importante. El análisis anatomo-patológico actual de la muestra comprueba la certeza del diagnóstico en nuestro paciente de muy larga supervivencia.Conclusiones: Múltiples variables son encontradas que influencian la larga supervivencia en distintas series, si bien los estudios analizados son muy heterogéneos resultando muy difícil la comparación entre ellos. La mayoría de los estudios referenciados pertenecen a bases de datos nacionales de distintos países que engloban a cientos de pacientes. Sería interesante fomentar el uso de una única base de datos en España que permita, entre otros, el análisis de estos pacientes de larga supervivencia afectos de glioblastoma (AU)
Introduction: In spite of the changes for the treatment of glioblastoma since 2005, we havent seen differences between long-survival patients of more than 10 years showing a value minor than 1%.Material and method: We realize a systematic analysis and identify important factors for long survivor patients. We also show an own case with more of 20 years of survival. We make a new pathological study of the old paraffin block of this patient.Results: The most important variable associated with long-survival between all multivariant studies is the age. When we try to find genetic and molecular alterations in glioblastoma associated with prolongated survival, the MGMT promoter methylation play the most important role. We find a correct diagnosis in the current analysis of our patient's sample with very long survival.Conclusions: Multiple variables are found that affect long survival of glioblastoma series but analyzed studies are very heterogeneous and it is very difficult comparation between them. Most articles we review are obtained from databases of different countries with hundreds of patients. It would be very interesting to promote the use of a single database in Spain that allows us to study these long-term glioblastoma survivors (AU)
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Humanos , Masculino , Adulto , Glioblastoma/mortalidad , Glioblastoma/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/diagnóstico por imagen , Glioblastoma/diagnóstico por imagen , Análisis de Supervivencia , Factores de Tiempo , PronósticoRESUMEN
OBJECTIVE: The aim of this study was evaluate the rate of sustained viral response (SVR) and the influence of different factors on the SVR in patients with chronic hepatitis C virus (HCV) infection treated with pegylated interferon alfa 2a and ribavirin. METHODS: We retrospectively analysed 272 naïve patients with chronic hepatitis C who had been treated for 24 weeks or 48 weeks and had been followed for an additional 6 months thereafter. RESULTS: Out of 272 patients, 243 completed the entire treatment. The overall SVR rate in intent-to-treat analysis was 66.5% and in treated patients was 74.5%. In an univariate analysis, the SVR was associated with age <40 years (84.4%),pre-treatment viral load <500.000 IU/ml (86.9%), non-1 genotype HCV (86.4%), non cirrhosis or pre-cirrhosis (76.5%), rapid virologic response (RVR) (91.4%) and early virologic response (EVR) (83.8%). In the multivariate logistic regression analysis, the presence of an infection caused by a non-1 genotype and to achieve ERV were independent predictors of SVR. The RVR and histological stage of liver disease were not included in the multivariate analysis because these data were not available in most of the patients. The PPV and NVP of RVR were 91.5% and 48.7% respectively, of EVR were 83.8% and 95.8% respectively and of complete EVR were 91.3% and 78.7%, respectively. CONCLUSIONS: The SVR was higher than in other studies. The genotype and EVR were independent factors to predict the effect of antiviral therapy. The EVR had a high NPV and the complete EVR a high PPV.