Effect of glucose variability on the mortality of adults aged 75 years and over during the first year of the COVID-19 pandemic.

BACKGROUND: To our knowledge, only one study has examined the association between glucose variability (GV) and mortality in the elderly population with diabetes. GV was assessed by HbA1c, and a J-shaped curve was observed in the relationship between HbA1c thresholds and mortality. No study of GV was conducted during the COVID-19 pandemic and its lockdown. This study aims to evaluate whether GV is an independent predictor of all-cause mortality in patients aged 75 years or older with and without COVID-19 who were followed during the first year of the COVID-19 pandemic and its lockdown measures. METHODS: This was a retrospective cohort study of 407,492 patients from the AGED-MADRID dataset aged 83.5 (SD 5.8) years; 63.2% were women, and 29.3% had diabetes. GV was measured by the coefficient of variation of fasting plasma glucose (CV-FPG) over 6 years of follow-up (2015-2020). The outcome measure was all-cause mortality in 2020. Four models of logistic regression were performed, from simple (age, sex) to fully adjusted, to assess the effect of CV-FPG on all-cause mortality. RESULTS: During follow-up, 34,925 patients died (14,999 women and 19,926 men), with an all-cause mortality rate of 822.3 per 10,000 person-years (95% confidence interval (CI), 813.7 to 822.3) (739 per 10,000; 95% CI 728.7 to 739.0 in women and 967.1 per 10,000; 95% CI 951.7 to 967.2 in men). The highest quartile of CV-FPG was significantly more common in the deceased group (40.1% vs. 23.6%; p < 0.001). In the fully adjusted model including dementia (Alzheimer's disease) and basal FPG, the odds ratio for mortality ranged from 1.88 to 2.06 in patients with T2DM and from 2.30 to 2.61 in patients with normoglycaemia, according to different sensitivity analyses. CONCLUSIONS: GV has clear implications for clinical practice, as its assessment as a risk prediction tool should be included in the routine follow-up of the elderly and in a comprehensive geriatric assessment. Electronic health records can incorporate tools that allow its calculation, and with this information, clinicians will have a broader view of the medium- and long-term prognosis of their patients.

PD-L1 Overexpression During Endotoxin Tolerance Impairs the Adaptive Immune Response in Septic Patients via HIF1α.

Sepsis, among other pathologies, is an endotoxin tolerance (ET)-related disease. On admission, we classified 48 patients with sepsis into 3 subgroups according to the ex vivo response to lipopolysaccharide. This response correlates with the Acute Physiology and Chronic Health Evaluation (APACHE) II score and the ET degree. Moreover, the ET-related classification determines the outcome of these patients. Programmed cell death-ligand 1 (PD-L1) expression on septic monocytes is also linked with ET status. In addition to the regulation of cytokine production, one of the hallmarks of ET that significantly affects patients with sepsis is T-cell proliferation impairment or a poor switch to the adaptive response. PD-L1/programmed cell death-1 (PD-1) blocking and knockdown assays on tolerant monocytes from both patients with sepsis and the in vitro model reverted the impaired adaptive response. Mechanistically, the transcription factor hypoxia-inducible factor-1α (HIF1α) has been translocated into the nucleus and drives PD-L1 expression during ET in human monocytes. This fact, together with patient classification according to the ex vivo lipopolysaccharide response, opens an interesting field of study and potential personalized clinical applications, not only for sepsis but also for all ET-associated pathologies.

The Spanish version of the Body Image Scale (S-BIS): psychometric properties in a sample of breast and gynaecological cancer patients.

PURPOSE: The aim of this study is to develop a Spanish version of the Body Image Scale (Hopwood et al. Eur J Cancer 37(2):189-197, 2001) and to analyze its psychometric properties in a sample of women with breast or gynaecological cancer. METHODS: The Spanish version of the Body Image Scale was developed using a forward and backward translation technique. A total sample of 100 women who had undergone radical surgery for breast (n = 50) or gynaecological cancer (n = 50) completed the scale. RESULTS: Factor analysis resulted in a single-factor solution, both in the total sample and in the two subgroups, accounting for >76 % variance. Internal consistency (Cronbach's alpha) was 0.960. The Spanish version of the Body Image Scale correlated negatively with self-esteem (r = -0.733), quality of life (r = -0.632) and age (r = -0.643) and positively with depression (r = 0.832) and anxiety (r = 0.564); all p values < 0.01. CONCLUSIONS: To our knowledge, this is the first study that provides a Spanish version of the Body Image Scale. Our results show a stable factorial structure between samples with a single-factor solution and good psychometric properties, suggesting that it is a suitable tool for measuring body image concerns among Spanish-speaking cancer patients. Its brevity and comprehensibility allow a quick assessment both in clinical and research settings.

Common mental disorders in primary health care: differences between Latin American-born and Spanish-born residents in Madrid, Spain.

PURPOSE: Our main objective was to estimate and compare the prevalence of the most common mental disorders between Latin American-born and Spanish-born patients in Madrid, Spain. We also analyzed sociodemographic factors associated with these disorders and the role of the length of residency for Latin American-born patients. METHODS: We performed a cross-sectional study to compare Latin American-born (n = 691) and Spanish-born outpatients (n = 903) from 15 primary health care centers in Madrid, Spain. The Primary Care Evaluation of Mental Disorders was used to diagnose common mental disorders. Sociodemographic, psychosocial, and migration data were collected. RESULTS: We detected common mental disorders in 49.9 % (95 % CI = 47.4-52.3 %) of the total sample. Values were higher in Latin American-born patients than in Spanish-born patients for any disorder (57.8 % vs. 43.9 %, p < 0.001), mood disorders (40.1 % vs. 34.8 %, p = 0.030), anxiety disorders (20.5 % vs. 15.3 %, p = 0.006), and somatoform disorders (18.1 % vs. 6.6 %, p < 0.001). There were no statistically significant differences in prevalence between Latin American-born patients with less than 5 years of residency and Latin American-born residents with 5 or more years of residency. Finally, multivariate analysis shows that gender, having/not having children, monthly income, geographic origin, and social support were significantly associated with several disorders. LIMITATIONS: The sample was neither population-based nor representative of the general immigrant or autochthonous populations. CONCLUSIONS: The study provides further evidence of the high prevalence of common mental disorders in Latin American-born patients in Spain compared with Spanish-born patients.

Psychological distress in women with breast and gynecological cancer treated with radical surgery.

OBJECTIVES: The objective of this study is to compare psychological distress (body image disturbance,self-esteem, depression, and anxiety) in women with breast or gynecological cancer treated by radical surgery. Additionally, another objective is to analyze the association between psychological distress and sociodemographic characteristics, medical history, and social support to produce a prediction model for the outcome measures. METHODS: A cross-sectional study was carried out with 100 women who had undergone radical surgery for breast or gynecological cancer. Both groups were divided into the following: younger than 50 years old and 50 years old or older. Body Image Scale, Rosenberg's Self-Esteem Scale, Beck Depression Inventory, and Beck Anxiety Inventory were used. RESULTS: Age had a significant main effect on psychological distress but the type of cancer did not.Younger women showed significantly greater distress than older women (p-values<0.001). A significant interaction between age and type of cancer was found, indicating that older women with breast cancer had worse body image and more depression than those with gynecological cancer (p-values 0.001); no significant differences were found between younger groups.The prediction model for increased body image disturbance and depression included the joint effect of the following variables: being younger, inactive occupational status, and post-adjuvant therapy side effects. For lower self-esteem, the variables were: being younger, post-adjuvant therapy side effects,and dissatisfaction with social support. And for higher anxiety, the sole variable included was post-adjuvant therapy side effects. CONCLUSIONS: Both mastectomy and hysterectomy/oophorectomy cause similar psychological distress in younger women, but mastectomy causes greater distress in older women than hysterectomy/oophorectomy.

Psychometric properties of the eight-item modified Medical Outcomes Study Social Support Survey based on Spanish outpatients.

PURPOSE: The aim of this study was to examine the psychometric properties of the modified Medical Outcomes Study Social Support Survey (mMOS-SS) in a primary healthcare setting (PHCS). METHODS: A cross-sectional descriptive study was carried out with Spanish outpatients (N = 903) from a PHCS. Subjects responded to the first eight items of the classic Medical Outcomes Study-Social Support Survey (MOS-SS), in effect the mMOS-SS, and immediately proceeded to give answers to the rest of the scale. Also, sociodemographic, self-reported health status and mood/anxiety disorders data were collected. Factor structure was analyzed using exploratory and confirmatory analysis, internal reliability was determined by Cronbach's standardized alpha, and consistency was evaluated by item-to-total score correlations. Evidences of validity were assessed by Spearman's rank correlations, and using the Mann-Whitney test or Kruskal-Wallis test as appropriate, of differences between the mMOS-SS and the MOS-SS. RESULTS: Mean scores for the MOS-SS (mean = 4.26, SD = 0.78) and mMOS-SS (mean = 4.34, SD = 0.74) are similar. Cronbach's alpha was 0.96 and 0.91, for the MOS-SS and mMOS-SS, respectively. Item-to-total score correlations of the MOS-SS and mMOS-SS are ≥0.64 and ≥0.70, respectively. Exploratory factor analysis (EFA) [56.63% variance, KMO=0.904; χ2=4396.27], and confirmatory factor analysis (CFA) [CFI=0.95; NNFI(TLI)=0.97; SRMR=0.05; χ2=296.81; RMSEA=0.17] showed a one-factor structure. CONCLUSIONS: Psychometric properties of the Spanish version of the mMOS-SS in outpatients attending a PHCS are adequate. Factor analysis confirmed a one-factor model with acceptable fit indices.

External validation of three diabetes prediction scores in a Spanish cohort: does adding high risk for depression improve the validation of the FINDRISC score (FINDRISC-MOOD)?

OBJECTIVES: To evaluate the external validity of the FINDRISC, DESIR and ADA risk scores for the prediction of diabetes in a Spanish population aged >45 years and to test the possible improvement of FINDRISC by adding a new variable of high risk of depression when Patient Health Questionnaire-9 (PHQ-9) questionnaire score ≥10 (FINDRISC-MOOD). DESIGN: Prospective population-based cohort study. SETTING: 10 primary healthcare centres in the north of the city of Madrid (Spain). PARTICIPANTS: A total of 1242 participants without a history of diabetes and with 2-hour oral glucose tolerance test (OGTT) plasma glucose <200 mg/dL (<11.1 mmol/L) were followed up for 7.3 years (median) using their electronic health records (EHRs) and telephone contact. PRIMARY AND SECONDARY OUTCOME MEASURES: Diabetes risk scores (FINDRISC, DESIR, ADA), PHQ-9 questionnaire and 2-hour-OGTT were measured at baseline. Incident diabetes was defined as treatment for diabetes, fasting plasma glucose ≥126 mg/dL (≥7.0 mmol/L), new EHR diagnosis or self-reported diagnosis. External validation was performed according to optimal cut-off, sensitivity, specificity and Youden Index. Comparison between diabetes risk scores, including FINDRISC-MOOD (original FINDRISC score plus five points if PHQ-9 ≥10), was measured by area under the receiver operating characteristic curve (AUROC). RESULTS: During follow-up, 104 (8.4%; 95% CI, 6.8 to 9.9) participants developed diabetes and 185 had a PHQ-9 score ≥10. The AUROC values were 0.70 (95% CI, 0.67 to 0.72) for FINDRISC-MOOD and 0.68 (95% CI, 0.65 to 0.71) for the original FINDRISC. The AUROCs for DESIR and ADA were 0.66 (95% CI, 0.63 to 0.68) and 0.66 (95% CI, 0.63 to 0.69), respectively. There were no significant differences in AUROC between FINDRISC-MOOD and the other scores. CONCLUSIONS: The results of FINDRISC-MOOD were like those of the other risk scores and do not allow it to be recommended for clinical use.

Validation of diagnosis of acute myocardial infarction and stroke in electronic medical records: a primary care cross-sectional study in Madrid, Spain (the e-MADVEVA Study).

OBJECTIVES: To validate the diagnoses of acute myocardial infarction (AMI) and stroke recorded in electronic medical records (EMR) and to estimate the population prevalence of both diseases in people aged ≥18 years. DESIGN: Cross-sectional validation study. SETTING: 45 primary care centres. PARTICIPANTS: Simple random sampling of diagnoses of AMI and stroke (International Classification of Primary Care-2 codes K75 and K90, respectively) registered by 55 physicians and random age-matched and sex-matched sampling of the records that included in primary care EMRs in Madrid (Spain). PRIMARY AND SECONDARY OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values and overall agreement were calculated using the kappa statistic. Applied gold standards were ECGs, brain imaging studies, hospital discharge reports, cardiology reports and neurology reports. In the case of AMI, the ESC/ACCF/AHA/WHF Expert Consensus Document was also used. Secondary outcomes were the estimated prevalence of both diseases considering the sensitivity and specificity obtained (true prevalence). RESULTS: The sensitivity of a diagnosis of AMI was 98.11% (95% CI, 96.29 to 99.03), and the specificity was 97.42% (95% CI, 95.44 to 98.55). The sensitivity of a diagnosis of stroke was 97.56% (95% CI, 95.56 to 98.68), and the specificity was 94.51% (95% CI, 91.96 to 96.28). No differences in the results were found after stratification by age and sex (both diseases). The prevalence of AMI and stroke was 1.38% and 1.27%, respectively. CONCLUSION: The validation results show that diagnoses of AMI and stroke in primary care EMRs constitute a helpful tool in epidemiological studies. The prevalence of AMI and stroke was lower than 2% in the population aged over 18 years.

Clinical and Demographic Characteristics of Centenarians versus Other Age Groups Over 75 Years with Hip Fractures.

Objective: The primary objective was to describe the clinical characteristics, management, and outcomes of centenarians with fragility hip fracture and compare them to other age groups. The secondary objective was to determine the variables associated with length of stay, in-hospital mortality and 30-day mortality. Materials and Methods: This is a secondary analysis of the Spanish National Hip Fracture Registry. We included patients ≥75 years admitted for fragility hip fractures in 86 Spanish hospitals between 2017 and 2019, dividing the sample into four age groups. The variables studied were baseline characteristics, type of fracture, management, length of stay, in-hospital mortality and 30-day mortality. Results: We included 25,938 patients (2888 were 75-79 years old; 14,762 octogenarians; 8,035 nonagenarians and 253 centenarians). Of the centenarians, 83% were women, 33% had severe dementia, 9% had severe dependency and 36% lived in residential care homes. Six out of ten had intertrochanteric fracture. Length of hospital stay was 8.6 days; in-hospital mortality was 10.3% and 30-day mortality 20.9%. Older age groups had more women, severe functional dependency, severe dementia, intertrochanteric fracture, living in care facilities and being discharged to nursing care. They had less frequent early mobilization, osteoporosis treatment and discharge to rehabilitation units. In-hospital and 30-day mortality were higher with increasing age. In centenarians, time to surgery >48 hours was independently associated with length of stay (correlation coefficient 3.99 [95% CI: 2.35-5.64; p<0.001]) and anaesthetic risk, based on an ASA score of V, was related to 30-day mortality (ASA score II [OR 0.25, 95% CI: 0.09-0.70; p=0.009] and ASA score III [OR 0.43, 95% CI: 0.19-0.96; p=0.039]). Conclusion: Centenarians had different clinical characteristics, management and outcomes. Although centenarians had worse outcomes, nearly 4 out of 5 centenarians were alive one month after surgery.

Effect of depression on mortality and cardiovascular morbidity in type 2 diabetes mellitus after 3 years follow up. The DIADEMA study protocol.

BACKGROUND: Type 2 diabetes mellitus and depression are highly prevalent diseases that are associated with an increased risk of cardiovascular disease and mortality. There is evidence about a bidirectional association between depressive symptoms and type 2 diabetes mellitus. However, prognostic implications of the joint effects of these two diseases on cardiovascular morbidity and mortality are not well-known. METHOD/DESIGN: A three-year, observational, prospective, cohort study, carried out in Primary Health Care Centres in Madrid (Spain). The project aims to analyze the effect of depression on cardiovascular events, all-cause and cardiovascular mortality in patients with type 2 diabetes mellitus, and to estimate a clinical predictive model of depression in these patients.The number of patients required is 3255, all them with type 2 diabetes mellitus, older than 18 years, who regularly visit their Primary Health Care Centres and agree to participate. They are chosen by simple random sampling from the list of patients with type 2 diabetes mellitus of each general practitioner.The main outcome measures are all-cause and cardiovascular mortality and cardiovascular morbidity; and exposure variable is the major depressive disorder.There will be a comparison between depressed and not depressed patients in all-cause mortality, cardiovascular mortality, coronary artery disease and stroke using the Chi-squared test. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors that might alter the effect recorded will be taken into account in this analysis. To assess the effect of depression on the mortality, a survival analysis will be used comparing the two groups using the log-rank test. The control of potential confounding variables will be performed by the construction of a Cox regression model. DISCUSSION: Our study's main contribution is to evaluate the increase in the risk of cardiovascular morbidity and mortality, in depressed Spanish adults with type 2 diabetes mellitus attended in Primary Health Care Setting. It would also be useful to identify subgroups of patients for which the interventions could be more beneficial.

Glycemic variability and all-cause mortality in a large prospective southern European cohort of patients with differences in glycemic status.

BACKGROUND: Few studies have analyzed the relationship between glucose variability (GV) and adverse health outcomes in patients with differences in glycemic status. The present study tests the hypothesis that GV predicts all-cause mortality regardless of glycemic status after simple adjustment (age and sex) and full adjustment (age, sex, cardiovascular disease, hypertension, use of aspirin, statins, GLP-1 receptor agonists, SGLT-2 inhibitors and DPP-4 inhibitors, baseline FPG and average HbA1c). METHODS: Prospective cohort study with 795 normoglycemic patients, 233 patients with prediabetes, and 4,102 patients with type 2 diabetes. GV was measured using the coefficient of variation of fasting plasma glucose (CV-FPG) over 12 years of follow-up. The outcome measure was all-cause mortality. RESULTS: A total of 1,223 patients (657 men, 566 women) died after a median of 9.8 years of follow-up, with an all-cause mortality rate of 23.35/1,000 person-years. In prediabetes or T2DM patients, the fourth quartile of CV-FPG exerted a significant effect on all-cause mortality after simple and full adjustment. A sensitivity analysis excluding participants who died during the first year of follow-up revealed the following results for the highest quartile in the fully adjusted model: overall, HR (95%CI) = 1.54 (1.26-1.89); dysglycemia (prediabetes and T2DM), HR = 1.41 (1.15-1.73); T2DM, HR = 1.36 (1.10-1.67). CONCLUSION: We found CV-FPG to be useful for measurement of GV. It could also be used for the prognostic stratification of patients with dysglycemia.

Improving hip fracture care in Spain: evolution of quality indicators in the Spanish National Hip Fracture Registry.

This study was carried out to analyze the evolution of the quality indicators in the Spanish National Hip Fracture Registry, after disseminating a series of recommendations based on available clinical practice guidelines to the participating hospitals. Six of the seven proposed quality indicators showed a significant improvement. PURPOSE: The Spanish National Hip Fracture Registry (RNFC) arises from the need to know the process and improve the quality of care. Our goal was to analyze the changes in the RNFC's quality indicators after an intervention based on disseminating specific recommendations among the participating hospitals, following available clinical practice guidelines. METHODS: Study comparing before and after performing an intervention in hospitals participating in the RNFC. Data from the hospitals that registered cases in 2017, and that kept registering cases in 2019. Seven quality indicators were chosen, and a standard to be achieved for each indicator was proposed. The intervention consisted in the dissemination of 25 recommendations with practical measures to improve each quality indicator, based on available clinical practice guidelines, by drafting and publishing a scientific paper and sending it via email and printed cards. Fulfilment of each quality indicator was measured after carrying out the intervention. RESULTS: Forty-three hospitals registered 2674 cases between January and May, 2017, and 8037 during 2019. The quality indicators chosen and the degree of compliance were (all with p<0.05): (1) surgery ≤48 h increased from 38.9 to 45.8%; (2) patients mobilised on the first postoperative day increased from 58.9 to 70.3%; (3) patients with anti-osteoporotic medication at discharge increased from 34.5 to 49.8%; (4) patients with calcium supplements at discharge increased from 48.7 to 62.8%; (5) patients with vitamin D supplements at discharge increased from 71.5 to 84.7%; (6) patients developing a grade >2 pressure ulcer during admission decreased from 6.5 to 5.0%; (7) patients able to move on their own at 1 month fell from 58.8 to 56.4%. More than 48% of hospitals improved the proposed indicators. CONCLUSION: Establishing quality indicators and standards and intervening through the dissemination of specific recommendations to improve these indicators achieved an improvement in hospital performance results on a national level.

The relationship between social support and self-reported health status in immigrants: an adjusted analysis in the Madrid Cross Sectional Study.

BACKGROUND: Social support is an important factor in the adaptation process of immigrants, helping for their integration in a new environment. The lack of social support may influence on well-being and health status. The aim of this study is to describe the social support of immigrant and native population and study the possible association between immigration and lack social support after adjusting for sociodemographic factors, income, stress and self-reported health status. METHODS: Cross-sectional population based study of immigrants and national patients without mental disorders of 15 urban primary health centers in the north-eastern area of Madrid. Participants provided information on social support, stress level, perceived health status and socio-economic characteristics. Descriptive and multiple logistic regression were conducted. RESULTS: The proportion of the global perception of social support among immigrants and natives was 79.2% and 94.2%, respectively. The lack of global social support adjusted prevalence ratio (PR) of immigrant was 2.72 (95% Confidence Interval=1.81-4.09), showing a significant association with being male (PR=2.26), having monthly income below 500 euros (PR=3.81) and suffering stress (PR=1.94). For the dimensions of lack of social support the higher association was being an immigrant and suffering stress. CONCLUSIONS: We conclude that with regardless of the level of monthly income, stress level, self-reported health status, and gender, immigrant status is directly associated with lack social support. The variable most strongly associated with lack social support has been monthly income below 500 euros.

[The Spanish National Hip Fractures Registry (RNFC) and the Minimum Basic Data Set (CMBD) are useful for research on hip fractures: comparison of two registries.] / El Registro Nacional de Fracturas de Cadera (RNFC) y el Conjunto Mínimo Básico de Datos son útiles para investigar sobre fracturas de cadera: comparación de ambos registros.

OBJECTIVE: National hip fracture registries have been established in several countries and recent publications show that the care process has been audited inspecting the representativeness according to quality standards. The aim of this study was to analyse if the Spanish National Hip Fracture Registry (RNFC) represents the Spanish population aged 75 and older admitted for hip fractures, and to compare its results regarding the care process with the national average, according to the National Inpatient register (Minimum Basic Dataset, CMBD). METHODS: The 2017-2018 National Minimum Basic Dataset (Conjunto Mínimo Básico de Datos, CMBD) was used as reference. For analysis, we included 83,110 cases from the CMBD and 21,130 from the RNFC. Eight common variables of both registries were selected for comparison. RESULTS: No significant differences were observed in the patient-related common variables (age, sex, type of fracture and fracture side), but statistically significant differences were found in the variables describing the care process (proportion of patients operated, deceased, surgical procedures and postoperative length of stay). CONCLUSIONS: The RNFC, designed as a convenience sample, is also representative of the population of patients aged 75 and older treated for hip fractures in Spain. However, there is a participation bias related to the professionals and the hospitals interested in voluntarily participating in a quality improvement program, which would explain the better results observed in the care process, compared to the national average as collected by the CMBD.

OBJETIVO: Los registros nacionales de fracturas de cadera se han establecido en varios países y publicaciones recientes muestran que el proceso de atención ha sido auditado para explorar su representatividad de acuerdo a estándares de calidad. El objetivo de este trabajo fue analizar si el Registro Nacional de Fracturas de Cadera (RNFC) es representativo de la población española de 75 o más años de edad ingresada por fractura de cadera, y comparar los resultados acerca del proceso asistencial con la media nacional según el Conjunto Mínimo Básico de Datos (CMBD). METODOS: Se empleó el CMBD de los años 2017-2018 como referencia. Para el análisis se incluyeron 83.110 casos del CMBD y 21.130 del RNFC. Se seleccionaron ocho variables comunes a ambos registros para ser comparadas. RESULTADOS: No se observaron diferencias significativas en las variables comunes paciente-dependientes (edad, sexo, tipo y lado de fractura), pero se hallaron diferencias significativas en las variables que describían el proceso asistencial (proporción de pacientes intervenidos, fallecidos, tipos de procedimiento quirúrgico y estancia postoperatoria). CONCLUSIONES: El RNFC, diseñado como muestra de conveniencia, es también representativa de la población de pacientes de 75 y más años, atendida por fractura de cadera en España. Sin embargo, existe un sesgo de participación relacionado con los profesionales y los hospitales interesados en participar voluntariamente en un programa voluntario de mejora de calidad que podría explicar los mejores resultados observados en el proceso asistencial, comparado con la media nacional según se recoge por el CMBD.

Differences in the baseline characteristics, management and outcomes of patients with hip fractures depending on their pre-fracture place of residence: the Spanish National Hip Fracture Registry (RNFC) cohort.

PURPOSE: One in four hip fracture patients comes from an aged care facility. This study aimed to compare the characteristics of these subjects with their community-dwelling counterparts at baseline, during hospitalization and 1-month post-fracture. METHODS: We analyzed data from a cohort of older adults admitted with hip fractures to 75 Spanish hospitals, collected prospectively in the Spanish National Hip Fracture Registry between 2016 and 2018. We classified participants according to pre-fracture residence: community dwellers vs. aged care facilities residents. We collected demographic records at baseline, along with variables relating to in-hospital evolution and discharge to geriatric rehabilitation units. Patients or relatives were interviewed at 1-month follow-up. RESULTS: Out of 18,262 patients, 4,422 (24.2%) lived in aged care facilities. Aged care facilities residents were older (median age: 89 vs. 86 years), less mobile (inability to walk independently: 20.8% vs. 9.4%) and had more cognitive impairment (Pfeiffer's SPMSQ > 3, 75.3% vs. 34.8%). They were more likely to receive conservative treatment (5.4% vs. 2.0%) and less likely to be mobilized early (58.2% vs. 63.0%). At discharge, they received less vitamin D supplements (68.5% vs. 72.4%), less anti-osteoporotic medication (29.3% vs. 44.3%), and were referred to geriatric rehabilitation units less frequently (5.4% vs. 27.5%). One-month post-fracture, 45% of aged care facilities residents compared to 28% of community dwellers experienced a severe gait decline. Aged care facilities residents had a higher one-month mortality (10.6% vs. 6.8%). CONCLUSION: Hip fracture patients from aged care facilities are more vulnerable than their community-dwelling peers and are managed differently both during hospitalization and at discharge. Gait decline is disproportionately higher among those admitted from aged care.

Tumor stem cells fuse with monocytes to form highly invasive tumor-hybrid cells.

The 'cancer cell fusion' theory is controversial due to the lack of methods available to identify hybrid cells and to follow the phenomenon in patients. However, it seems to be one of the best explanations for both the origin and metastasis of primary tumors. Herein, we co-cultured lung cancer stem cells with human monocytes and analyzed the dynamics and properties of tumor-hybrid cells (THC), as well as the molecular mechanisms beneath this fusion process by several techniques: electron-microscopy, karyotyping, CRISPR-Cas9, RNA-seq, immunostaining, signaling blockage, among others. Moreover, mice models were assessed for in vivo characterization of hybrids colonization and invasiveness. Then, the presence of THCs in bloodstream and samples from primary and metastatic lesions were detected by FACS and immunofluorescence protocols, and their correlations with TNM stages established. Our data indicate that the generation of THCs depends on the expression of CD36 on tumor stem cells and the oxidative state and polarization of monocytes, the latter being strongly influenced by microenvironmental fluctuations. Highly oxidized M2-like monocytes show the strongest affinity to fuse with tumor stem cells. THCs are able to proliferate, colonize and invade organs. THC-specific cell surface signature CD36+CD14+PANK+ allows identifying them in matched primary tumor tissues and metastases as well as in bloodstream from patients with lung cancer, thus functioning as a biomarker. THCs levels in circulation correlate with TNM classification. Our results suggest that THCs are involved in both origin and spread of metastatic cells. Furthermore, they might set the bases for future therapies to avoid or eradicate lung cancer metastasis.

First proposal of quality indicators and standards and recommendations to improve the healthcare in the Spanish National Registry of Hip Fracture.

BACKGROUND: The Spanish National Hip Fracture Registry (or Registro Nacional de Fractura de Cadera, RNFC) is a database of hip fracture patients admitted to Spanish hospitals. Its goals include assessment and continuous improvement of the care process. OBJECTIVES: To (1) establish a series of indicators, (2) evaluate their initial fulfillment, (3) propose quality standards, (4) suggest recommendations to facilitate standards compliance, and (5) monitor the indicators. METHOD: The indicators fulfilled the criteria of (1) evaluating the process or outcome, (2) being clinically relevant for patients, (3) being modifiable through changes in healthcare practice, and (4) being considered important by the RNFC participants. The first quartile obtained by the group of hospitals in each of the respective variables was proposed as the standard. The Indicators Advisory Committee (IAC) elaborated a list of recommendations for each indicator, based on the available evidence. RESULTS: Seven indicators were chosen. These indicators (its baseline compliance vs. the standard to be reached, respectively) were: the proportion of patients receiving surgery within 48h (44% vs. 63%), mobilized the first postoperative day (56% vs. 86%), with antiosteoporotic medication at discharge (32% vs. 61%), with calcium supplements at discharge (46% vs. 77%), with vitamin D supplements at discharge (67% vs. 92%), who developed pressure ulcers during hospitalization (7.2% vs. 2.1%) and with independent mobility at 30 days (58% vs. 70%). The IAC has established 25 recommendations for improving care. CONCLUSION: The indicators and standards chosen are presented, as well as the list of recommendations. This process completes the first step to improve quality of care. The results will be evaluated 6 months after implementing the recommendations.

Pseudomonas aeruginosa colonization causes PD-L1 overexpression on monocytes, impairing the adaptive immune response in patients with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is an endotoxin tolerance (ET)-related disease. Given that increased PD-L1 has been reported in ET, its expression and physiological effects on cystic fibrosis monocytes should be studied. METHODS: We analyzed the phenotype and ex vivo response of immune system cells in 32 patients with CF, 19 of them colonized by Pseudomonas aeruginosa. An in vitro model was developed of Pseudomonas aeruginosa colonization using purified lipopolysaccharides (LPS) from one of the most prevalent strains in patients with CF (a CF-adapted Pseudomonas aeruginosa ST395 clone). Changes in the immune response, including cytokine production and T-lymphocyte proliferation, as well as expression of PD-L1, were evaluated. RESULTS: PD-L1 was overexpressed in the monocytes of patients with CF compared with healthy volunteers, and levels of this immune checkpoint were associated with Pseudomonas aeruginosa colonization. In addition, patients with Pseudomonas aeruginosa colonization showed a patent ET status, including poor inflammatory response, reduced HLA-DR expression and T-lymphocyte proliferation impairment. PD-L1/PD-1 blocking assays reverted the impaired adaptive response. Ultimately, monocytes from healthy volunteers cultured in the presence of the clinically relevant strain of Pseudomonas aeruginosa or serum collected from patients with CF colonized by Pseudomonas aeruginosa reproduced the previous observed features. CONCLUSIONS: Pseudomonas aeruginosa colonization in patients with CF was associated with PD-L1 overexpression and impaired T cell response, and LPS from this pathogen induced the observed phenotype. Our findings open new avenues for the use of anti-PD-1/PD-L1 immunotherapy in patients with CF who are colonized by Pseudomonas aeruginosa.