Mortality, Functional Status, and Quality of Life after 5 Years of Patients Admitted to Critical Care for Spontaneous Intracerebral Hemorrhage.

BACKGROUND: The objective of this study was to assess long-term outcome in patients with spontaneous intracerebral hemorrhage admitted to the intensive care unit. METHODS: Mortality and Glasgow Outcome Scale, Barthel Index, and 5-level EQ-5D version (EQ-5D-5L) scores were analyzed in a multicenter cohort study of three Spanish hospitals (336 patients). Mortality was also analyzed in the Medical Information Mart for Intensive Care III (MIMIC-III) database. RESULTS: The median (25th percentile-75th percentile) age was 62 (50-70) years, the median Glasgow Coma Score was 7 (4-11) points, and the median Acute Physiology and Chronic Health disease Classification System II (APACHE-II) score was 21 (15-26) points. Hospital mortality was 54.17%, mortality at 90 days was 56%, mortality at 1 year was 59.2%, and mortality at 5 years was 66.4%. In the Glasgow Outcome Scale, a normal or disabled self-sufficient situation was recorded in 21.5% of patients at 6 months, in 25.5% of patients after 1 year, and in 22.1% of patients after 5 years of follow-up (4.5% missing). The Barthel Index score of survivors improved over time: 50 (25-80) points at 6 months, 70 (35-95) points at 1 year, and 90 (40-100) points at 5 years (p < 0.001). Quality of life evaluated with the EQ-5D-5L at 1 year and 5 years indicated that greater than 50% of patients had no problems or slight problems in all items (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). In the MIMIC-III study (N = 1354), hospital mortality was 31.83% and was 40.5% at 90 days and 56.2% after 5 years. CONCLUSIONS: In patients admitted to the intensive care unit with a diagnosis of nontraumatic intracerebral hemorrhage, hospital mortality up to 90 days after admission is very high. Between 90 days and 5 years after admission, mortality is not high. A large percentage of survivors presented a significant deficit in quality of life and functional status, although with progressive improvement over time. Five years after the hemorrhagic stroke, a survival of 30% was observed, with a good functional status seen in 20% of patients who had been admitted to the hospital.

External Validation and Recalibration of a Mortality Prediction Model for Patients with Ischaemic Stroke.

BACKGROUND: Stroke is a highly prevalent disease that can provoke severe disability. We evaluate a predictive model based on the Minimum Basic Data Set (MBDS) compiled by the Spain Health Ministry, obtained for the period 2008-2012 for patients with ischaemic stroke in Spain, to establish the model's validity and to optimise its calibration. The MBDS is the main clinical-administrative database for hospitalisations recorded in Spain, and to our knowledge, no predictive models for stroke mortality have previously been developed using this resource. The main study aim is to perform an external validation and recalibration of the coefficients of this predictive model with respect to a chronologically later cohort. MATERIAL AND METHODS: External validation (testing the model on a different cohort to assess its performance) and recalibration (validation with optimisation of model coefficients) were performed using the MBDS for patients admitted for ischaemic stroke in the period 2016-2018. A cohort study was designed, in which a recalibrated model was obtained by applying the variables of the original model without their coefficients. The variables from the original model were then applied to the subsequent cohort, together with the coefficients from the initial model. The areas under the curve (AUC) of the recalibration and the external validation procedure were compared. RESULTS: The recalibrated model produced an AUC of 0.743 and was composed of the following variables: age (odds ratio, OR:1.073), female sex (OR:1.143), ischaemic heart disease (OR:1.192), hypertension (OR:0.719), atrial fibrillation (OR:1.414), hyperlipidaemia (OR:0.652), heart failure (OR:2.133) and posterior circulation stroke (OR: 0.755). External validation produced an AUC of 0.726. CONCLUSIONS: The recalibrated clinical model thus obtained presented moderate-high discriminant ability and was generalisable to predict death for patients with ischaemic stroke. Rigorous external validation slightly decreased the AUC but confirmed the validity of the baseline model for the chronologically later cohort.

TGFß Governs the Pleiotropic Activity of NDRG1 in Triple-Negative Breast Cancer Progression.

In triple-negative breast cancer (TNBC), the pleiotropic NDRG1 (N-Myc downstream regulated gene 1) promotes progression and worse survival, yet contradictory results were documented, and the mechanisms remain unknown. Phosphorylation and localization could drive NDRG1 pleiotropy, nonetheless, their role in TNBC progression and clinical outcome was not investigated. We found enhanced p-NDRG1 (Thr346) by TGFß1 and explored whether it drives NDRG1 pleiotropy and TNBC progression. In tissue microarrays of 81 TNBC patients, we identified that staining and localization of NDRG1 and p-NDRG1 (Thr346) are biomarkers and risk factors associated with shorter overall survival. We found that TGFß1 leads NDRG1, downstream of GSK3ß, and upstream of NF-κB, to differentially regulate migration, invasion, epithelial-mesenchymal transition, tumor initiation, and maintenance of different populations of cancer stem cells (CSCs), depending on the progression stage of tumor cells, and the combination of TGFß and GSK3ß inhibitors impaired CSCs. The present study revealed the striking importance to assess both total NDRG1 and p-NDRG1 (Thr346) positiveness and subcellular localization to evaluate patient prognosis and their stratification. NDRG1 pleiotropy is driven by TGFß to differentially promote metastasis and/or maintenance of CSCs at different stages of tumor progression, which could be abrogated by the inhibition of TGFß and GSK3ß.

TFG-ß Nuclear Staining as a Potential Relapse Risk Factor in Early-Stage Non-Small-Cell Lung Cancer.

Nowadays, the impact of the tumor-immune microenvironment (TME) in non-small-cell lung cancer (NSCLC) prognosis and treatment response remains unclear. Thus, we evaluated the expression of PD-L1, tumor-infiltrating lymphocytes (TILs), and transforming growth factor beta (TGF-ß) in NSCLC to identify differences in TME, detect possible new prognostic factors, and assess their relationship. We retrospectively analyzed 55 samples from patients who underwent NSCLC surgery and had over a 5-year follow-up. PD-L1 expression was determined by immunohistochemistry following standard techniques. The presence of TILs was evaluated at low magnification and classified into two categories, "intense" and "non-intense". Cytoplasmic TGF-ß staining visualization was divided into four categories, and unequivocal nuclear staining in >1% of viable tumor cells was defined as "present" or "absent". Our aim was to identify differences in disease-free survival (DFS) and overall survival (OS). Tumor stage was the only objective prognostic factor for OS. PD-L1 expression and the presence of TILs had no prognostic impact, neither their combination. There seems to be a lower expression of PD-L1 and a higher expression of TILs in early stages of the disease. Our TGF-ß nuclear staining analysis was promising, since it was associated with worse DFS, revealing this protein as a possible prognostic biomarker of recurrence for resectable NSCLC.

Valoración y seguimiento de los pacientes con sospecha de COVID-19 en la primera ola pandémica en una zona urbana de Andalucía / Assessment and follow-up of patients with suspected COVID-19 in the first pandemic wave in an urban area of Andalusia (Spain)

Objetivos: Conocer las características de la atención inicial y el seguimiento telefónico de pacientes con sospecha de COVID-19 en la primera ola de la pandemia. Diseño: Observacional retrospectivo (auditoría de historias clínicas).Emplazamiento: Centro de salud urbano. Participantes: Casos probables de SARS-CoV-2 (15/03/2020 a 15/06/2020). Mediciones principales Ámbito de atención inicial y seguimiento telefónico (número de llamadas y duración). Variables sociodemográficas (incluyendo estructura familiar). Curso clínico (sintomatología, vulnerabilidad, pruebas, ingreso hospitalario y desenlace). Resultados Trescientos uno pacientes (51,5 [±17,8] años, 23% vulnerables, 17% estructura familiar no nuclear). Valoración inicial en el centro de salud (59,8%: telefónica; 25,2%: presencial). En urgencias hospitalarias (11%) presentaron síntomas similares que en atención primaria, predominan estructuras familiares no nucleares (p<0,05; test χ2), realizando más pruebas (p<0,05; test χ2). En domicilio (3,9%) son pacientes ancianos vulnerables (p<0,01, test ANOVA). El seguimiento telefónico duró 17,1 [±10,3] días con 8,2 [±4,4] llamadas, superior si provenían de urgencias o domicilio (p<0,03; test ANOVA). Se incrementa tras ≥2 consultas presenciales (OR: 4,8), la presencia de síntomas de alarma (OR: 2,3) y la edad ≥45 años (OR: 2,0). Se realizaron pocas pruebas de confirmación (19,3% antigénicas, 13% serologías). El 15,3% ingresos hospitalarios (todos valorados en centros de salud), con 6,3% casos severos y 2,3% exitus. Conclusión Durante la primera ola de la pandemia, la población optó por ser atendida de forma telemática en su centro de salud. Las valoraciones iniciales en urgencias del hospital se relacionan con la falta de apoyo social, pero no con mayor gravedad clínica. El seguimiento telefónico fue aceptado por la población y permitió seleccionar a los pacientes con peor curso clínico.

ObjectiveTo know the characteristics of the initial care and telephone follow-up of patients with suspected COVID-19 in the first wave of the pandemic. Design: Observational, retrospective (audit of medical records).Location: Urban Primary Care Center of Andalusia (Spain). Participants: Probable cases of SARS-CoV-2 (from 20/03/15 to 20/06/15). Principal measurements Initial medical assessment (place and modality) and telephone follow-up (number of calls and duration). Sociodemographic variables (including family structure). Clinical course (symptoms, vulnerability, tests, hospital admission and outcome). Results Three hundred one patients (51.5±17.8 years; 23% vulnerable people; 17% non-nuclear family structure). First assessment in Primary Care by phone (59.8%) and face-to-face (25.2%). At the hospital emergency department (11%), patients were more frequently from non-nuclear families (P<.05 χ2) and more tests were carried out (P<.05 χ2) despite having similar symptoms. Vulnerable elderly patients needed home health care (P<.01 ANOVA). 8.2±4.4 follow-up phone calls were made per patient, for 17.1±10.3 days. It increases after ≥2 face-to-face consultations (OR 4.8), the presence of alarm symptoms (OR 2.3) and age ≥45 years (OR 2.0). Few confirmatory tests were performed (19.3% antigenic, 13% serology). The 15.3% hospital admissions (all assessed previously in Primary Care), with 6.3% severe cases and 2.3% death. Conclusion Population chose to be attended in Primary Care during the pandemic first wave, above all by phone. Telephone follow-up was well accepted and useful to select patients with serious complications. Initial medical assessment in the hospital emergency department was related to a lack of social support but not with greater clinical severity.

[Assessment and follow-up of patients with suspected COVID-19 in the first pandemic wave in an urban area of Andalusia (Spain)]. / Valoración y seguimiento de los pacientes con sospecha de COVID-19 en la primera ola pandémica en una zona urbana de Andalucía.

OBJECTIVE: To know the characteristics of the initial care and telephone follow-up of patients with suspected COVID-19 in the first wave of the pandemic. DESIGN: Observational, retrospective (audit of medical records). LOCATION: Urban Primary Care Center of Andalusia (Spain). PARTICIPANTS: Probable cases of SARS-CoV-2 (from 20/03/15 to 20/06/15). PRINCIPAL MEASUREMENTS: Initial medical assessment (place and modality) and telephone follow-up (number of calls and duration). Sociodemographic variables (including family structure). Clinical course (symptoms, vulnerability, tests, hospital admission and outcome). RESULTS: Three hundred one patients (51.5±17.8 years; 23% vulnerable people; 17% non-nuclear family structure). First assessment in Primary Care by phone (59.8%) and face-to-face (25.2%). At the hospital emergency department (11%), patients were more frequently from non-nuclear families (P<.05 χ2) and more tests were carried out (P<.05 χ2) despite having similar symptoms. Vulnerable elderly patients needed home health care (P<.01 ANOVA). 8.2±4.4 follow-up phone calls were made per patient, for 17.1±10.3 days. It increases after ≥2 face-to-face consultations (OR 4.8), the presence of alarm symptoms (OR 2.3) and age ≥45 years (OR 2.0). Few confirmatory tests were performed (19.3% antigenic, 13% serology). The 15.3% hospital admissions (all assessed previously in Primary Care), with 6.3% severe cases and 2.3% death. CONCLUSION: Population chose to be attended in Primary Care during the pandemic first wave, above all by phone. Telephone follow-up was well accepted and useful to select patients with serious complications. Initial medical assessment in the hospital emergency department was related to a lack of social support but not with greater clinical severity.

Multidisciplinary Unit Improves Pregnancy Outcomes in Women with Rheumatic Diseases and Hereditary Thrombophilias: An Observational Study.

Rheumatic diseases (RD) and hereditary thrombophilias (HT) can be associated with high-risk pregnancies. This study describes obstetric outcomes after receiving medical care at a multidisciplinary consultation (MC) and compares adverse neonatal outcomes (ANOs) before and after medical care at an MC. This study is a retrospective observational study among pregnant women with RD and HT treated at an MC of a university hospital (southern Spain) from 2012 to 2018. Absolute risk reduction (ARR) and number needed to treat (NNT) were calculated. A total of 198 pregnancies were registered in 143 women (112 with RD, 31 with HT), with 191 (96.5%) pregnancies without ANOs and seven (3.5%) pregnancies with some ANOs (five miscarriages and two foetal deaths). Results previous to the MC showed 60.8% of women had more than one miscarriage, with 4.2% experiencing foetal death. MC reduced the ANO rate by AAR = 60.1% (95%CI: 51.6-68.7%). The NNT to avoid one miscarriage was 1.74 (95%CI: 1.5-2.1) and to avoid one foetal death NNT = 35.75 (95CI%: 15.2-90.9). A total of 84.8% of newborns and 93.2% of women did not experience any complication. As a conclusion, the follow-up of RD or HT pregnant women in the MC drastically reduced the risk of ANOs in this population with a previous high risk.

Predictive Model of the Risk of In-Hospital Mortality in Colorectal Cancer Surgery, Based on the Minimum Basic Data Set.

BACKGROUND: Various models have been proposed to predict mortality rates for hospital patients undergoing colorectal cancer surgery. However, none have been developed in Spain using clinical administrative databases and none are based exclusively on the variables available upon admission. Our study aim is to detect factors associated with in-hospital mortality in patients undergoing surgery for colorectal cancer and, on this basis, to generate a predictive mortality score. METHODS: A population cohort for analysis was obtained as all hospital admissions for colorectal cancer during the period 2008-2014, according to the Spanish Minimum Basic Data Set. The main measure was actual and expected mortality after the application of the considered mathematical model. A logistic regression model and a mortality score were created, and internal validation was performed. RESULTS: 115,841 hospitalization episodes were studied. Of these, 80% were included in the training set. The variables associated with in-hospital mortality were age (OR: 1.06, 95%CI: 1.05-1.06), urgent admission (OR: 4.68, 95% CI: 4.36-5.02), pulmonary disease (OR: 1.43, 95%CI: 1.28-1.60), stroke (OR: 1.87, 95%CI: 1.53-2.29) and renal insufficiency (OR: 7.26, 95%CI: 6.65-7.94). The level of discrimination (area under the curve) was 0.83. CONCLUSIONS: This mortality model is the first to be based on administrative clinical databases and hospitalization episodes. The model achieves a moderate-high level of discrimination.

Activating Transcription Factor 4 Modulates TGFß-Induced Aggressiveness in Triple-Negative Breast Cancer via SMAD2/3/4 and mTORC2 Signaling.

Purpose: On the basis of the identified stress-independent cellular functions of activating transcription factor 4 (ATF4), we reported enhanced ATF4 levels in MCF10A cells treated with TGFß1. ATF4 is overexpressed in patients with triple-negative breast cancer (TNBC), but its impact on patient survival and the underlying mechanisms remain unknown. We aimed to determine ATF4 effects on patients with breast cancer survival and TNBC aggressiveness, and the relationships between TGFß and ATF4. Defining the signaling pathways may help us identify a cell signaling-tailored gene signature.Experimental Design: Patient survival data were determined by Kaplan-Meier analysis. Relationship between TGFß and ATF4, their effects on aggressiveness (tumor proliferation, metastasis, and stemness), and the underlying pathways were analyzed in three TNBC cell lines and in vivo using patient-derived xenografts (PDX).Results: ATF4 overexpression correlated with TNBC patient survival decrease and a SMAD-dependent crosstalk between ATF4 and TGFß was identified. ATF4 expression inhibition reduced migration, invasiveness, mammosphere-forming efficiency, proliferation, epithelial-mesenchymal transition, and antiapoptotic and stemness marker levels. In PDX models, ATF4 silencing decreased metastases, tumor growth, and relapse after chemotherapy. ATF4 was shown to be active downstream of SMAD2/3/4 and mTORC2, regulating TGFß/SMAD and mTOR/RAC1-RHOA pathways independently of stress. We defined an eight-gene signature with prognostic potential, altered in 45% of 2,509 patients with breast cancer.Conclusions: ATF4 may represent a valuable prognostic biomarker and therapeutic target in patients with TNBC, and we identified a cell signaling pathway-based gene signature that may contribute to the development of combinatorial targeted therapies for breast cancer. Clin Cancer Res; 24(22); 5697-709. ©2018 AACR.

Prevalencia y factores asociados a la práctica del consejo clínico contra el consumo de drogas entre los especialistas internos residentes de Andalucía (España) / Prevalence and factors associated with clinical counselling on drug use among internal specialists residents of Andalusia (Spain)

OBJETIVOS: Conocer la frecuencia de la oferta de consejo clínico contra el consumo de alcohol, tabaco y drogas ilegales por los especialistas internos residentes (EIR) y los factores relacionados con dicho consejo. DISEÑO: Estudio multicéntrico transversal mediante encuesta autoadministrada. EMPLAZAMIENTO Y PARTICIPANTES: EIR de Andalucía (España), mediante correo electrónico. MEDICIONES PRINCIPALES: Consejo declarado contra alcohol, tabaco y drogas ilegales, mediante escala Likert categorizada como ®frecuente»/®no frecuente». Variables independientes: edad/sexo, especialidad, país de origen y características del consumo de drogas. Análisis mediante regresión logística. RESULTADOS: Cuatro mil doscientos cuarenta y cinco participantes con el 66% de respuestas, 29% no respondedores y 5% mala cumplimentación; edad media 29,1 ± DE 5,1 años, 69% mujeres, 89% nacionalidad española, 84% con formación en medicina (hospitalaria 73%, medicina familiar 27%). El consejo frecuente contra tabaco (85%) y alcohol (82%) es superior al de drogas ilegales (56%; p < 0,001 test de Chi cuadrado). El consejo frecuente contra el alcohol se relaciona con la especialidad (medicina familiar: OR = 2,8, IC 95% [1,4-4,6]; enfermería: OR = 2,5 [1,7-4,4]) y la edad del primer consumo alcohólico (OR = 1,07; [1,03-1,1]). Para el tabaco hay relación con la especialidad (medicina familiar: OR = 12,9 [7,6-21,9]; enfermería: OR = 8,4, [4,3-16,5]), el tabaquismo (OR = 1,5 [1,2-2,0]) y edad del primer consumo alcohólico (OR = 1,06 [1,01-1,1]), más importante para el vino (OR = 1,1 [1,04-1,3]). Aconsejar contra drogas ilegales se relaciona con la edad del primer consumo alcohólico (OR = 1,09 [1,05-1,1]) y el tabaquismo (OR = 0,58 [0,4-0,7]). CONCLUSIÓN: Hay una alta oferta de consejo contra el consumo por los EIR, aunque llamativamente menor para drogas ilegales. Los factores que influyen son tanto elementos formativos de su propia especialidad como el consumo personal de alcohol y tabaco, que deben ser tenidos en cuenta para una mejora de esta actividad preventiva

OBJECTIVES: To determine the percentage of women who have had a Pap smear in the last 5 years, and the place where it was carried out. To detect cytological abnormalities and precursors of cervical cancer in un-screened or inadequately screened women and the prevalence of HPV-positive determinations. DESIGN: Cross sectional study. SETTING: Natahoyo Health Centre, Gijón (Spain). PARTICIPANTS: Women aged 40-50 years living in the area and assigned to the Health Centre. METHODS: The information was collected from databases, telephone and home surveys. There was active recruitment of unscreened women or inadequately screened in Primary Care as well as offering to perform cytology and HPV determination. RESULTS: Of the 1420 women aged 40 to 50 years, 1236 (87%) had cytology in the last 5 years, and 184 women (13%) had no screening or it was inadequate. Of these 184 women, 108 (58.7%) agreed to have cytology and HPV test performed. No high-grade cervical dysplasia was diagnosed. The prevalence of HPV-positive was 8.3%. CONCLUSIONS: In our population there is a high coverage of opportunistic screening for cervical cancer. The active recruitment of women who were not in the screening program was not useful

[Prevalence and factors associated with clinical counselling on drug use among internal specialists residents of Andalusia (Spain)]. / Prevalencia y factores asociados a la práctica del consejo clínico contra el consumo de drogas entre los especialistas internos residentes de Andalucía (España).

OBJECTIVES: To determine the frequency of offering clinical counseling against the consumption of alcohol, tobacco and illegal drugs by internal specialist residents (EIR) of Andalusia, and the factors related to such advice. DESIGN: Multicenter cross-sectional study by self-administered questionnaire sent by mail. SETTING AND PARTICIPANTS: EIR of Andalusia. MAIN MEASUREMENTS: The questionnaire collected the frequency of counseling against the use of alcohol, tobacco and illegal drugs (dependent variable). INDEPENDENT VARIABLES: age/gender, specialty, drug consumption and Fagerström test. RESULTS: Out of a total of 4245 participants, 66% responded, 29% did not respond, and 5% poorly completed questionnaires. The mean age was 29.1(±SD 5.1) years, 69% female, 89% Spanish nationality, 84% in medical training (73% hospital, 27% family medicine). The frequency of counseling against tobacco (85%) and alcohol (82%) is higher than illegal drugs (56%, p<.001, χ(2) test). Counseling against alcohol consumption is related to family medicine (OR=2.8; 95% CI [1.4-4.6]) and nursing (OR=2.5 [1.7-4.4]), and the age of first alcohol consumption (OR=1.07 [1.03-1.1]). Counseling against smoking is related to family medicine (OR=12.9;[7.6-21.9]) and nursing (OR=8.4;[4.3-16.5]), personal consumption of tobacco (OR=1.5 [1.2-2.0]), and wine (OR=1.1 [1.04-1.3]), and age of first alcohol consumption (OR=1.06 [1.01-1.1]). Counseling against illegal drugs is related to the age of first alcohol consumption (OR=1.09 [1.05-1.1]) and smoking (OR=.58 [.4-.7]). CONCLUSION: There is a high frequency of counseling against consumption of tobacco and alcohol by EIR, although remarkably smaller for illegal drugs. The influencing factors are both formative elements of their own specialty such as personal consumption of alcohol and tobacco, which should be considered for improvement of this preventive activity.