Surprising and novel multivariate sequential patterns using odds ratio for temporal evolution in healthcare.

BACKGROUND: Pattern mining techniques are helpful tools when extracting new knowledge in real practice, but the overwhelming number of patterns is still a limiting factor in the health-care domain. Current efforts concerning the definition of measures of interest for patterns are focused on reducing the number of patterns and quantifying their relevance (utility/usefulness). However, although the temporal dimension plays a key role in medical records, few efforts have been made to extract temporal knowledge about the patient's evolution from multivariate sequential patterns. METHODS: In this paper, we propose a method to extract a new type of patterns in the clinical domain called Jumping Diagnostic Odds Ratio Sequential Patterns (JDORSP). The aim of this method is to employ the odds ratio to identify a concise set of sequential patterns that represent a patient's state with a statistically significant protection factor (i.e., a pattern associated with patients that survive) and those extensions whose evolution suddenly changes the patient's clinical state, thus making the sequential patterns a statistically significant risk factor (i.e., a pattern associated with patients that do not survive), or vice versa. RESULTS: The results of our experiments highlight that our method reduces the number of sequential patterns obtained with state-of-the-art pattern reduction methods by over 95%. Only by achieving this drastic reduction can medical experts carry out a comprehensive clinical evaluation of the patterns that might be considered medical knowledge regarding the temporal evolution of the patients. We have evaluated the surprisingness and relevance of the sequential patterns with clinicians, and the most interesting fact is the high surprisingness of the extensions of the patterns that become a protection factor, that is, the patients that recover after several days of being at high risk of dying. CONCLUSIONS: Our proposed method with which to extract JDORSP generates a set of interpretable multivariate sequential patterns with new knowledge regarding the temporal evolution of the patients. The number of patterns is greatly reduced when compared to those generated by other methods and measures of interest. An additional advantage of this method is that it does not require any parameters or thresholds, and that the reduced number of patterns allows a manual evaluation.

Clustering COVID-19 ARDS patients through the first days of ICU admission. An analysis of the CIBERESUCICOVID Cohort.

BACKGROUND: Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster. METHODS: Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3. RESULTS: Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [n = 1025] versus 27.3% [n = 383] at baseline, and 49% [n = 1023] versus 20.6% [n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3. CONCLUSIONS: During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis.

Influenza A: New Therapeutic Targets for a Deadly Disease / Gripe A: nuevas dianas terapéuticas para una enfermedad mortal

No disponible

Necrolisis epidérmica tóxica: un paradigma de enfermedad crítica / Toxic epidermal necrolysis: a paradigm of critical illness

RESUMEN La necrolisis epidérmica tóxica es una reacción cutánea adversa de tipo inmunológico secundaria en la mayor parte de los casos a la administración de un fármaco. La necrolisis epidérmica tóxica, el síndrome de Steven Johnson y el eritema exudativo multiforme forman parte del mismo espectro de enfermedad. La mortalidad de la necrolisis epidérmica tóxica es alrededor del 30%. La fisiopatología de la necrolisis epidérmica tóxica es semejante en muchos aspectos a la de las quemaduras dérmicas superficiales. La afectación mucosa del epitelio ocular y genital se asocia con secuelas graves si no se trata de forma temprana. Se acepta en general que los pacientes con necrolisis epidérmica tóxica son tratados mejor en unidades de grandes quemados, donde existe experiencia en el manejo de enfermos con pérdida cutánea extensa. El tratamiento es de soporte, eliminación y cobertura con derivados biosintéticos de la piel de las zonas afectadas, tratamiento de la afectación mucosa, y tratamiento inmunosupresor específico. De los tratamientos ensayados sólo se usa actualmente en la mayor parte de los centros la inmunoglobulina G y la ciclosporina A, aun cuando no existe evidencia sólida para recomendar ningún tratamiento específico. Entre los aspectos particulares del tratamiento de esta enfermedad se encuentra la prevención de secuelas relacionadas con la formación de sinequias, los cuidados oculares para prevenir secuelas graves que pueden conducir a la ceguera, y el tratamiento específico inmunosupresor. Un mejor conocimiento de los principios del manejo de la necrolisis epidérmica tóxica llevará a un mejor manejo de la enfermedad, a una mayor supervivencia y una menor prevalencia de las secuelas.

ABSTRACT Toxic epidermal necrolysis is an adverse immunological skin reaction secondary in most cases to the administration of a drug. Toxic epidermal necrolysis, Stevens-Johnson syndrome, and multiform exudative erythema are part of the same disease spectrum. The mortality rate from toxic epidermal necrolysis is approximately 30%. The pathophysiology of toxic epidermal necrolysis is similar in many respects to that of superficial skin burns. Mucosal involvement of the ocular and genital epithelium is associated with serious sequelae if the condition is not treated early. It is generally accepted that patients with toxic epidermal necrolysis are better treated in burn units, which are experienced in the management of patients with extensive skin loss. Treatment includes support, elimination, and coverage with biosynthetic derivatives of the skin in affected areas, treatment of mucosal involvement, and specific immunosuppressive treatment. Of the treatments tested, only immunoglobulin G and cyclosporin A are currently used in most centers, even though there is no solid evidence to recommend any specific treatment. The particular aspects of the treatment of this disease include the prevention of sequelae related to the formation of synechiae, eye care to prevent serious sequelae that can lead to blindness, and specific immunosuppressive treatment. Better knowledge of the management principles of toxic epidermal necrolysis will lead to better disease management, higher survival rates, and lower prevalence of sequelae.

Medicina de sistemas: una nueva visión de la práctica clínica / Systems Medicine: A New Approach to Clinical Practice

La gran mayoría de las enfermedades respiratorias son consideradas patologías complejas puesto que su susceptibilidad o desenlace están influidos por la interacción entre factores dependientes del huésped (genéticos, comorbilidad, edad, etc.) y del ambiente (exposición a microorganismos y alérgenos, tratamiento administrado, etc.).El enfoque reduccionista ha sido muy importante para la comprensión de los diversos componentes de un sistema. La biología o medicina de sistemas es una aproximación complementaria cuyo objetivo es el análisis de las interacciones entre los componentes dentro de un nivel de organización (genoma, transcriptoma, proteoma) y posteriormente entre los distintos niveles. Las actuales aplicaciones de la medicina de sistemas incluyen la interpretación de la patogénesis y fisiopatología de las enfermedades, el descubrimiento de biomarcadores, el diseño de nuevas estrategias terapéuticas y la elaboración de modelos computacionales para los distintos procesos biológicos. En la presente revisión se exponen las principales nociones sobre la teoría que subyace a la medicina de sistemas así como sus aplicaciones en algunos procesos biológicos del ser humano

Most respiratory diseases are considered complex diseases as their susceptibility and outcomes are determined by the interaction between host-dependent factors (genetic factors, comorbidities, etc.) and environmental factors (exposure to microorganisms or allergens, treatments received, etc.).The reductionist approach in the study of diseases has been of fundamental importance for the understanding of the different components of a system. Systems biology or systems medicine is a complementary approach aimed at analyzing the interactions between the different components within one organizational level (genome, transcriptome, proteome), and then between the different levels. Systems medicine is currently used for the interpretation and understanding of the pathogenesis and pathophysiology of different diseases, biomarker discovery, design of innovative therapeutic targets, and the drawing up of computational models for different biological processes. In this review we discuss the most relevant concepts of the theory underlying systems medicine, as well as its applications in the various biological processes in humans

Update in the management of severe traumatic brain injury

Traumatic brain injury is the main cause of death and disability in the young population, which presumes a large number of years of potential life lost and a great economic impact. Vital and functional outcomes after suffering a traumatic brain injury depend both on the severity of the initial biomechanical impact (primary injury) and on the presence and the severity of systemic or intracranial insults that magnify and/or produce new brain injuries, the so-called secondary injuries. Currently, no treatment in effective in improving functional recovery, except for usual medical care. Therefore, the main purpose of the care provided to a patient with severe cranial trauma is based on preventing and treating secondary brain injuries by maintaining an adequate cerebral perfusion and oxygenation. Increased intracranial pressure is associated with mortality and with unfavorable functional outcomes is patients with severe traumatic brain injury. The main clinical practice guidelines recommend using a number of staggered therapeutic measures. However, although these measures seem to be efficient in reducing intracranial pressure, this effect is not often translated into clinical improvement. This review describes the essential principles of the management of patients with severe traumatic brain injury in intensive care units.

Experiencia en el tratamiento de las fístulas rectouretrales post-prostatectomía radical / Experience in the treatment of rectourethral fistulae after radical prostatectomy

OBJETIVO: Presentar las características clínicas de las fistulas rectouretrales (FRU) tras prostatectomía radical (PR) así como nuestra experiencia en el manejo y tratamiento de las mismas.MÉTODO: Presentamos la experiencia de nuestro centro en el tratamiento de las FRU atendiendo a sus características clínicas y la presencia de factores de complejidad asociada. En todos los casos, tras la historia clínica y el examen físico el estudio se completó con uretrocistografía, enema opaco y uretrocistoscopia. Desde enero de 2000 a julio de 2010 hemos tratado 12 pacientes con FRU. La edad media fue de 64 años (rango 56-74 años). La etiología fue cirugía abierta en dos casos y cirugía laparoscópica en diez. La clínica se presentó en un plazo de 4 a 60 días.RESULTADOS: En nuestra experiencia los hallazgos endoscópicos y radiológicos tuvieron una buena correlación. Dos fístulas fueron pequeñas -menos de 5 mm- y en la vertiente uretral de la anastomosis permitiendo el tratamiento conservador el cierre espontáneo. Diez pacientes presentaron fístulas mayores, en la vertiente vesical de la anastomosis o con complejidad asociada, que requirieron para su resolución de un abordaje transesfinteriano posterior de York-Mason con buena recuperación urinaria y fecal posterior.CONCLUSIÓN: La FRU tras PR es una complicación relevante y de difícil resolución. Proponemos la cirugía reconstructiva precoz en las FRU grandes o con complejidad asociada. El cierre con abordaje transesfinteriano posterior de York-Mason ha permitido la resolución de la FRU en todos los casos(AU)

OBJECTIVES: To report the clinical charac-teristics of recto-urethral fistula (RUF) after radical prosta-tectomy (RP) as well as our experience managing them.METHODS: We present our experience in the treatment of RUF based on their clinical characteristics and the pre-sence of associated complexity factors. After medical history and physical examination, the diagnostic work up was completed in all cases with urethrograms, cystoscopy and barium enema. From January 2000 to July 2010 we treated 12 patients with RUF. Mean age was 64 years (range 56-74 years). The etiology was open sur-gery in two cases and laparoscopic surgery in ten. Clinical presentation varied from 4 to 60 days after surgery.RESULTS: In our experience, endoscopic and radiolo-gical findings were well correlated. Two fistulae were small -less than 5 mm- on the urethral side of the anasto-mosis allowing spontaneous closure after conservative treatment. Ten patients had larger fistulas on the bladder side of the anastomosis and/or were associated with com-plexity factors that required a posterior trans-sphincteric York-Mason approach for resolution, with good reco-very of urinary and fecal continence.CONCLUSION: The RUF is a significant compli-cation after RP and it is difficult to solve. We propose early recons-tructive surgery in large or complex RUF. The posterior trans-sphincteric York-Mason approach has allowed the repair in all cases(AU)

Diferencias clínico-patológicas y tabaquismo en función del sexo en una cohorte de pacientes con carcinoma de células transicionales de vejiga: un estudio retrospectivo / Clinical-pathological differences and smoking habit depending on gender in a cohort of patients with transitional cell carcinoma of the bladder: retrospective study

OBJETIVO: Es conocida la mayor incidencia de carcinoma de células transicionales (CCT) de vejiga en los varones, generalmente atribuida a una mayor exposición al efecto de los carcinógenos. A pesar de que se ha comunicado que la evolución puede ser especialmente adversa en las mujeres debido a factores socioeconómicos o biológicos, no han sido suficientemente estudiadas las diferencias clínico-patológicas del CCT en el momento del diagnóstico entre el hombre y la mujer. El objetivo de este estudio es analizar las diferencias en la exposición al tabaco, el grado y el estadio tumoral del CCT primario de vejiga en función del sexo.MÉTODOS: Se han incluido todos los diagnósticos consecutivos de CCT primario de vejiga realizados en nuestra institución entre 1990 y 2009. Se analizan, de forma retrospectiva, edad, hábito tabáquico, sintomatología, grado tumoral (OMS 1973), tamaño tumoral, multiplicidad y estadio TNM, comparándolas entre hombres y mujeres. Para el análisis estadístico se empleó la U de Mann-Withney como test no paramétrico y el test de Chi-cuadrado para la comparación de frecuencias.RESULTADOS: Se han analizado 1196 pacientes (992 hombres y 204 mujeres) con una razón observada de 5:1. Se han encontrado diferencias significativas en la edad (69 años vs 73 años), hábito tabáquico (46.5% vs 11.2%) y estadio músculo-infiltrante (12.1% vs 18.1%). Corrigiendo por el hábito tabáquico, las mujeres no fumadoras presentan tumores de mayor tamaño y grado con una frecuencia de enfermedad músculo-infiltrante 3 veces superior a los varones no fumadores e igualando a los fumadores.CONCLUSIÓN: El CCT de vejiga tiene mayor incidencia en los varones. En esta serie, las mujeres tenían una edad más avanzada en el momento del diagnóstico y presentan con más frecuencia enfermedad músculo-infiltrante afectando especialmente a las no fumadoras. Hacen falta estudios dirigidos a analizar el potencial impacto del tabaquismo pasivo que justifiquen estos resultados(AU)

OBJECTIVES: The increased incidence of transitional cell carcinoma (TCC) of the bladder in men is known, generally attributed to greater exposure to the effect carcinogenic products. Although it has been reported that cancer-specific outcome can be particularly adverse in women due to socioeconomic or biological factors, clinical-pathological differences of TCC at the time of diagnosis have not been sufficiently studied. The aim of this study is to analyze whether there are gender-related differences in grade and tumor stage in primary bladder TCC.METHODS: All consecutive primary bladder TCC diagnoses made in our institution between 1990 and 2009 have been included. We retrospectively analyzed age, smoking, symptoms at presentation, tumor grade (WHO 1973), tumor size and number, and TNM stage, comparing men and women. Statistical analysis was conducted using the Mann-Whitney U test as non-parametric test and Chi-squared test to compare frequencies.RESULTS : We analyzed 1196 patients (992 males and 204 females) with a 5:1 ratio. We found significant differences in age (69 years vs. 73 years), smoking (46.5% vs. 11.2%) and muscle-invasive stage (12.1% vs. 18.1%). Correcting by tobacco consumption, never-smoker women have larger and more aggressive tumors with a frequency of muscle-invasive disease three times higher than male never-smokers and equaling to male current-smokers.CONCLUSION: TCC of the bladder is more frequent in males than females. In this series, women are older at the time of diagnosis and most often affected by muscle-invasive disease particularly in never-smokers. We need studies to analyze the potential impact of passive smoking to justify these results(AU)

Estudio genético en el síndrome de QT largo en nuestro medio / Genetic testing of patients with long QT syndrome

El síndrome de QT largo congénito tiene su causa principal en mutaciones de los genes KCNQ1, KCNH2 y SCN5A. Nos proponemos analizar la prevalencia de mutaciones en estos genes en nuestra serie de pacientes con síndrome de QT largo y fibrilación ventricular idiopática. Se incluyó a 9 pacientes con síndrome de QT largo y 4 con fibrilación ventricular idiopática. Se estudió a los familiares de primer grado de los probandos con genotipo positivo. Encontramos mutaciones missense en 7 pacientes con síndrome de QT largo y en 2 con fibrilación ventricular idiopática. El 71,4% de las mutaciones fueron en KCNH2 y el 28,6% en SCN5A. No se halló ninguna mutación en KCNQ1. Sólo dos mutaciones estaban previamente descritas. En 6 familiares de los 19 estudiados se encontró una mutación. En conclusión, en nuestra experiencia inicial el estudio genético tuvo una alta sensibilidad para el diagnóstico de síndrome de QT largo. El gen más frecuentemente mutado fue KCNH2 (AU)

Congenital long QT syndrome is mainly caused by mutations in the KCNQ1, KCNH2 and SCN5A genes. The aim of this study was to investigate the prevalence of mutations in these three genes in patients with long QT syndrome or idiopathic ventricular fibrillation seen at our center. The study included nine patients with long QT syndrome and four with idiopathic ventricular fibrillation. The first-degree relatives of genotype-positive probands were also investigated. Missensemutationswere found in seven patients with long QT syndrome and two with idiopathic ventricular fibrillation. Overall, 71.4% of mutations were in KCNH2 and 28.6% were in SCN5A. No mutations in KCNQ1 were found. Only two mutations had been previously observed. Mutations were also found in six of the 19 relatives studied. In conclusion, our initial experience shows that genetic testing had a high sensitivity for diagnosing long QT syndrome. Mutations were found most frequently in the KCNH2 gene (AU)