Longitudinal outcomes of obeticholic acid therapy in ursodiol-nonresponsive primary biliary cholangitis: Stratifying the impact of add-on fibrates in real-world practice.

BACKGROUND: Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline phosphatase [ALP] and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long-term effectiveness of second-line treatments remains uncertain. AIMS: To evaluate the long-term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation). METHODS: We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non-responsive PBC patients (Paris-II criteria) from Spain and Portugal who received OCA ± fibrates. RESULTS: Of 255 patients, median follow-up was 35.1 months (IQR: 20.2-53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE-PBC and 5-year UK-PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension. CONCLUSION: Triple therapy was superior in achieving therapeutic goals in UDCA-nonresponsive PBC. Decompensation was linked to pre-existing portal hypertension.

Diagnostic accuracy of lumbar CT and MRI in the evaluation of chronic low back pain without red flag symptoms.

BACKGROUND: Low back pain (LBP) is one of the most frequent reasons for medical consultation. Most of the patients will have nonspecific LBP, which usually are self-limited episodes. It is unclear which of the diagnostic imaging pathways is most effective and costeffective and how the imaging impacts on patient treatment. Imaging techniques are usually indicated if symptoms remain after 6 weeks. Magnetic resonance imaging (MRI) is the diagnostic imaging examination of choice in lumbar spine evaluation of low back pain; however, availability of MRI is limited. OBJECTIVES: To evaluate the diagnostic accuracy of computed tomography (CT) with MRI (as standard of reference) in the evaluation of chronic low back pain (LBP) without red flags symptoms. To compare the results obtained by two radiologists with different grades of experience. MATERIALS AND METHODS: Patients with chronic low back pain without red flags symptoms were retrospectively reviewed by two observers with different level of experience. Patients included had undergone a lumbar or abdominal CT and an MRI within a year. Once the radiological information was collected, it was then statistically reviewed. The aim of the statistical analysis is to identify the equivalence between both diagnostic techniques. To this end, sensitivity, specificity and validity index were calculated. In addition, intra and inter-observer reliability were measured by Cohen's kappa values and also using the McNemar test. RESULTS: 340 lumbar levels were evaluated from 68 adult patients with chronic low back pain or sciatica. 63.2% of them were women, with an average age of 60.3 years (SD 14.7). CT shows high values of sensitivity and specificity (>80%) in most of the items evaluated, but sensitivity was low for the evaluation of density of the disc (40%) and for the detection of disc herniation (55%). Moreover, agreement between MRI and CT in most of these items was substantial or almost perfect (Cohen's kappa-coefficient > 0'8), excluding Modic changes (kappa = 0.497), degenerative changes (kappa0.688), signal of the disc (kappa = 0.327) and disc herniation (kappa = 0.639). Finally, agreement between both observers is mostly high (kappa > 0.8). Foraminal stenosis, canal stenosis and the grade of the canal stenosis were overdiagnosed by the inexperienced observer in the evaluation of CT images. CONCLUSIONS AND SIGNIFICANCE: CT is as sensitive as lumbar MRI in the evaluation of most of the items analysed, excluding Modic changes, degenerative changes, signal of the disc and disc herniation. In addition, these results are obtained regardless the experience of the radiologist. The rising use of diagnostic medical imaging and the improvement of image quality brings the opportunity of making a second look of abdominal CT in search of causes of LBP. Thereby, inappropriate medical imaging could be avoided (2). In addition, it would allow to reduce MRI waiting list and prioritize other patients with more severe pathology than LBP.

Allergy to cypress and olive pollen: Clinical phenotypes and allergen recognition.

BACKGROUND AND OBJECTIVES: Cypress and olive pollen are the most prevalent sensitizer trees in the Mediterranean area. Some patients exhibit a dual sensitization which has not been well documented yet. To identify the allergens involved in the dual cypress and olive allergy (C+O) and study the relationship between phenotype and allergen sensitization. METHODS: C+O patients were selected. Monosensitized subjects to olive or cypress were used as reference. Specific IgE to whole extracts and purified allergens from olive and cypress were performed. Immunoblotting was done to analyze IgG and IgE-binding using olive polyclonal antibodies and patients' sera, respectively. Mutual immunoblotting inhibition of olive and cypress extracts, and inhibition of cypress extract immunoblotting with olive allergens were performed. Multiple correspondence analysis and hierarchical cluster classifications were conducted to analyze the relationships between C+O clinical presentation (symptoms, seasonality) and allergen profile. RESULTS: C+O patients were clustered in 4 phenotypes. The most frequent one (58.4%) was rhinoconjunctivitis in winter (February) and spring (May), with asthma in 38% of subjects. Ole e 1 and Cup s 1 were the major allergens. Homologous proteins to Ole e 1, Ole e 9 and Ole e 11 in cypress pollen were identified and these olive allergens inhibit IgE-binding to cypress extract. CONCLUSIONS: The exclusive C+O allergy results from co-sensitization to Cup s 1 and Ole e 1, and to cross-reactivity due to Ole e 1-like, Ole e 9-like and Ole e 11-like allergens not described previously, and translates into 4 clinical phenotypes of winter and/or spring or perennial rhinoconjunctivitis with and without asthma.

Mild sensory symptoms during SARS-CoV-2 infection among healthcare professionals.

INTRODUCTION: It is not yet possible to estimate the proportion of patients with COVID-19 who present distinguishable classical neurological symptoms and syndromes. The objective of this study is to estimate the incidence of sensory symptoms (hypoaesthesia, paraesthesia, and hyperalgesia) in physicians who have presented the disease at Hospital Universitario Fundación Alcorcón (HUFA) in Madrid; to establish the relationship between sensory symptoms and the presence of other signs of infection; and to study their association with the severity of COVID-19. METHODS: We conducted a descriptive, cross-sectional, retrospective, observational study. HUFA physicians who presented SARS-CoV-2 infection between 1 March and 25 July 2020 were included in the study. A voluntary, anonymous survey was distributed via corporate email. Sociodemographic and clinical characteristics were collected from professionals with PCR- or serology-confirmed COVID-19. RESULTS: The survey was sent to 801 physicians and we received 89 responses. The mean age of respondents was 38.28 years. A total of 17.98% presented sensory symptoms. A significant relationship was found between the presence of paraesthesia and cough, fever, myalgia, asthaenia, and dyspnoea. A significant relationship was also found between paraesthesia and the need for treatment and admission due to COVID-19. Sensory symptoms were present from the fifth day of illness in 87.4% of cases. CONCLUSIONS: SARS-CoV-2 infection can be associated with sensory symptoms, mostly in severe cases. Sensory symptoms often appear after a time interval, and may be caused by a parainfectious syndrome with an autoimmunity background.

Population based study of morbidity and mortality rates associated to radical prostatectomy cases in Spain.

INTRODUCTION: There is no population-based study that accounts for the number of radical prostatectomies (RP) carried out in Spain, nor regarding the morbidity and mortality of this intervention. Our objective is to study the morbidity and mortality of RP in Spain from 2011 to 2015 and to evaluate the geographic variation. MATERIAL AND METHODS: We designed a retrospective observational study of all patients submitted to RP in Spain during five consecutive years (2011-2015). The data was extracted from the «Conjunto Mínimo Básico de Datos¼ (CMBD). We have evaluated geographic variations in terms of morbidity and hospital stay, and the impact of the mean annual surgical volume for each center on these variables. RESULTS: Between 2011-2015, a total of 37,725 RPs were performed in 221 Spanish public hospitals. The mean age of the series was 63.9±3.23 years. Of all RPs, 50% were performed through an open approach, and 43.4% have been operated on in hospitals with <500 beds. We observed an important variability in the distribution of the cases operated on in the different regions. The regions that perform more RPs are Andalusia, Catalonia, Galicia, and Madrid. Our study shows a complication rate of 8.6%, with hemorrhage and the need for transfusion being the most frequent (5.3 and 4%, respectively). There are significant differences in bleeding rates and hospital stay among regions, which are maintained after adjusting for patient characteristics and type of hospital. When studying the annual surgical volume of each hospital, we find that the impact on the rate of hemorrhage or transfusion is linear; however, hospital stay remains stable at around 5 days from 60 RPs/year. CONCLUSIONS: In national terms, morbidity and mortality rates after RP are comparable to those described in the literature. This study reveals a clear dispersion in the hospitals that carry out this intervention, showing clear differences in terms of morbidity and hospital stay between the different regions.

Incidence of Fatal Anaphylaxis: A Systematic Review of Observational Studies.

BACKGROUND: Fatal anaphylaxis is very rare, with an incidence ranging from 0.5 to 1 deaths per million person-years. OBJECTIVE: Based on a systematic review, we aimed to explain differences in the reported incidence of fatal anaphylaxis based on the methodological and demographic factors addressed in the various studies. METHODS: We searched PubMed/MEDLINE, EMBASE, and the Web of Science for relevant retrospective and prospective cohort studies and registry studies that had assessed the anaphylaxis mortality rate for the population of a country or for an administrative region. The research strategy was based on combining the term "anaphylaxis" with "death", "study design", and "main outcomes" (incidence). RESULTS: A total of 46 studies met the study criteria and included 16,541 deaths. The range of the anaphylaxis mortality rate for all causes of anaphylaxis was 0.002-2.51 deaths per million person-years. Fatal anaphylaxis due to food (range 0.002-0.29) was rarer than deaths due to drugs (range 0.004-0.56) or Hymenoptera venom (range 0.02-0.61). The frequency of deaths due to anaphylaxis by drugs increased during the study period (IRR per year, 1.02; 95%CI, 1.00-1.04). We detected considerable heterogeneity in almost all of the meta-analyses carried out. CONCLUSION: The incidence of fatal anaphylaxis is very low and differs according to the various subgroups analyzed. The studies were very heterogeneous. Fatal anaphylaxis due to food seems to be less common than fatal anaphylaxis due to drugs or Hymenoptera venom.

Differential risk for COVID-19 in the first wave of the disease among Spaniards and migrants from different areas of the world living in Spain.

INTRODUCTION AND OBJECTIVES: Little is known regarding the relevance of racial/ethnic background to the risk for COVID-19 infection, particularly in Europe. We evaluated the risk of COVID-19 among migrants from different areas of the world within the context of universal free access to medical care. MATERIALS AND METHODS: We conducted a population-based cohort analysis of the cumulative incidence of PCR-confirmed COVID-19 among adult residents of Alcorcon (Spain) in the first wave of the disease up to April 25, 2020. RESULTS: The crude cumulative incidence among migrants (n = 20419) was higher than among Spaniards (n = 131599): 8.81 and 6.51 and per 1000 inhabitants, respectively (p <  .001), but differed by region of origin. As per a negative binomial regression adjusted for age and sex, relative risk (RR) for COVID-19 for individuals from Europe, Asia, or North Africa was not significantly different from Spaniards. In contrast, a markedly increased risk was found in people from Sub-Saharan Africa (RR 3.66, 95% confidence interval (CI) 1.42-9.41, p =  .007), the Caribbean (RR 6.35, 95% CI 3.83-10.55, p <  .001), and Latin America (RR 6.92, 95% CI 4.49-10.67, p <  .001). CONCLUSIONS: Migrants from Sub-Saharan Africa, the Caribbean, and Latin America exhibited increased risk for COVID-19 as compared to Spaniards or migrants from Europe, North Africa, or Asia. Our data suggest ethnic background may play a role in risk for COVID-19. Migrants from some areas of the world may merit closer attention for both clinical and epidemiological reasons.

Melanocytic lesions with peripheral globules: results of an observational prospective study in 154 high-risk melanoma patients under digital dermoscopy follow-up evaluated with reflectance confocal microscopy.

BACKGROUND: The management of melanocytic lesions with peripheral globules (MLPGs) is usually age-dependent and can be challenging in high-risk melanoma patients. OBJECTIVES: To evaluate clinical, dermoscopic and reflectance confocal microscopy (RCM) features of MLPG in patients under digital dermoscopic surveillance. To know whether dermoscopic or RCM findings correlate with histologic diagnosis and the accuracy of the dermoscopy-RCM compared with histopathology. METHODS: During 24 months, we prospectively enrolled MLPG in patients under digital dermoscopy follow-up. All were evaluated by dermoscopy and RCM and excised for histologic examination. RESULTS: We enrolled 154 patients, mean age 42.45 years (18.78-73.19). Three melanomas and 19 dysplastic naevi (DNs) were diagnosed. There were no significant differences in the age of the patients (P = 0.662). MLPGs with diameter of 6 mm or more and asymmetry in two axes were associated with melanoma (P = 0.01, P = 0.003). Patients with more than one MLPG were less likely to have melanoma. Blue-grey and red colours were more frequent in melanoma (P = 0.013 and P = 0.000). Different sizes and shapes of PG were associated with DN and melanoma (P = 0.000 and P = 0.001). In a new lesion, PG in <25% of the circumference was related to malignancy (P = 0.010). RCM signs of malignancy were related to melanoma: pagetoid cells (P = 0.000), non-edged papillae (P = 0.001), atypical junctional thickenings (P = 0.000) and atypical cells at the dermal-epidermal junction (P = 0.000). Dense irregular nests were associated to melanoma (P = 0.019). Dermoscopy and confocal evaluation were able to diagnose 100% of melanomas and 84.21% of DNs. The kappa coefficient between dermoscopy-RCM vs. histology was 0.76. CONCLUSIONS: We recommend to excise a MLPG when it presents asymmetry in two axes, 6 or more mm, new lesion with PG in less than the 25% of the circumference, irregular size and shape PGs and irregular dense nests on RCM, regardless of the patient's age.

[Strategy for planning and execution of a large-scale SARS-CoV-2 seroprevalence study on teaching hospital workers during a pandemic situation]. / Estrategia de planificación y ejecución de un estudio a gran escala de seroprevalencia de SARS-CoV-2 en trabajadores de un hospital universitario durante una situación de pandemia.

OBJECTIVE: To describe the planning and execution process of a massive seroprevalence study for SARS-CoV-2 in professionals of the Hospital Universitario Fundación Alcorcón (HUFA) (Spain). METHODS: A description is presented of the plan designed and developed at the HUFA for the execution of the extraction of the samples for serology from all the professionals who worked in the hospital between 14 and 29 April 2020. A descriptive analysis of the participation of the professionals in the study is carried out. Extraction areas, health personnel, and execution times were planned. A total of 2326 extractions were assigned to health personnel, the remaining extractions were assigned to workers from external companies. RESULTS: A total of 2641 workers (90.5%) out of 2918 candidates participated in the study. The professional category most analysed was nursing with 28.3% (n = 590). The percentage of compliance with schedule planning was 28.6%. Up to a maximum of 298 daily extractions were planned. The busiest day was the 4th day of the study with 399 extractions. CONCLUSIONS: The organising of such a large study, with a 100% coverage of those who worked in the hospital, and with such a great response from the workers involved, has led to obtaining results of high reliability in the seroprevalence study carried out. Although the percentage of participation was very high, the level of compliance with the planning was low.

Association Between Severity of Anaphylaxis and Co-occurrence of Respiratory Diseases: A Systematic Review and Meta-analysis of Observational Studies.

BACKGROUND AND OBJECTIVE: Asthma is very prevalent in all grades of severity of anaphylaxis. Asthma and chronic obstructive pulmonary disease (COPD) have been associated with the severity of anaphylaxis. Objective: We carried out a systematic review and meta-analysis to assess the influence of respiratory diseases on the severity of anaphylaxis. METHODS: We searched PubMed/MEDLINE, EMBASE, and the Web of Science for observational studies. The target studies were those that compared the severity of anaphylaxis between patients who had or did not have respiratory diseases. RESULTS: A total of 13 studies assessed the severity of anaphylaxis in respiratory disease. Respiratory disease increased the severity of anaphylaxis (OR, 1.87; 95%CI, 1.30-2.70), as did asthma (OR, 1.89; 95%CI, 1.26-2.83). For the meta-analysis of all studies (adjusted and nonadjusted), COPD increased the severity of anaphylaxis (OR, 2.47; 95%CI, 1.46-4.18). In the case of asthma studies, only 1 study assessed the influence of severity of asthma on severity of anaphylaxis. CONCLUSIONS: Evidence showing that respiratory disease increases the severity of anaphylaxis is low to moderate, although studies do not usually assess the importance of severity of asthma.

HAE-AS: A Specific Disease Activity Scale for Hereditary Angioedema With C1-Inhibitor Deficiency.

BACKGROUND AND OBJECTIVE: The activity of hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) varies between patients and within individual patients. Objective: This study aims to develop a disease activity scale for C1-INH-HAE (HAE-AS) with sound measurement properties. METHODS: Eleven countries participated in a prospective multicenter cohort study. A clinical questionnaire was self-completed by 290 adult patients with C1-INH-HAE. Patients also completed 2 quality of life scales, the SF-36v2 and the HAE-QoL. Rasch analysis and classic psychometric methods were used to preselect a series of clinical items: number of attacks by location and number of treated attacks, emergency room visits, psychological/psychiatric treatment, missed school/workdays in the previous 6 months; general health; and impairment in everyday work/activities due to pain. RESULTS: The mean (SD) age was 41.5 (14.7; range, 18-84) years, and 69% were females. The final 12-item Rasch model showed that the HAE-AS had satisfactory reliability (person separation index, 0.748), local item independence, unidimensionality, and no item bias by age or sex. The HAE-AS provided scores in a linear measure, with a mean of 10.66 (3.92; range, 0-30). Further analysis with classic psychometric methods indicated that the HAE-AS linear measure presented moderate-to-high convergent validity with quality of life scales (SF-36v2: physical component, r=-0.33; mental component, 0.555; HAE-QoL, -0.61), and good discriminative validity by age, sex, and disease severity (P<.05). CONCLUSIONS: The HAE-AS is a short, valid, reliable, and psychometrically sound measure of the activity of C1-INH-HAE that could prove useful for research studies.

[Differential risk for COVID-19 in the first wave of the disease among Spaniards and migrants from different areas of the world living in Spain]. / Riesgo de COVID-19 en españoles y migrantes de distintas zonas del mundo residentes en España en la primera oleada de la enfermedad.

INTRODUCTION AND OBJECTIVES: Little is known regarding the relevance of racial/ethnic background to the risk for COVID-19 infection, particularly in Europe. We evaluated the risk of COVID-19 among migrants from different areas of the world within the context of universal free access to medical care. MATERIAL AND METHODS: We conducted a population-based cohort analysis of the cumulative incidence of PCR-confirmed COVID-19 among adult residents of Alcorcon (Spain) in the first wave of the disease up to April 25, 2020. RESULTS: The crude cumulative incidence among migrants (n = 20,419) was higher than among Spaniards (n = 131,599): 8.81 and 6.51 and per 1,000 inhabitants, respectively (p < .001), but differed by region of origin. As per a negative binomial regression adjusted for age and sex, relative risk (RR) for COVID-19 for individuals from Europe, Asia, or North Africa was not significantly different from Spaniards. In contrast, a markedly increased risk was found for people from Sub-Saharan Africa (RR 3.66, 95% confidence interval (CI) 1.42-9.41, p = .007), the Caribbean (RR 6.35, 95% CI 3.83-10.55, p < .001), and Latin America (RR 6.92, 95% CI 4.49-10.67, p < .001). CONCLUSIONS: Migrants from Sub-Saharan Africa, the Caribbean, and Latin America exhibited increased risk for COVID-19 as compared to Spaniards or migrants from Europe, North Africa, or Asia. Our data suggest that the ethnic background may play a role in risk for COVID-19. Migrants from some areas of the world may merit closer attention for both clinical and epidemiological reasons.

Differential risk for COVID-19 in the first wave of the disease among Spaniards and migrants from different areas of the world living in Spain. / Riesgo de COVID-19 en españoles y migrantes de distintas zonas del mundo residentes en España en la primera oleada de la enfermedad.

INTRODUCTION AND OBJECTIVES: Little is known regarding the relevance of racial/ethnic background to the risk for COVID-19 infection, particularly in Europe. We evaluated the risk of COVID-19 among migrants from different areas of the world within the context of universal free access to medical care. MATERIAL AND METHODS: We conducted a population-based cohort analysis of the cumulative incidence of PCR-confirmed COVID-19 among adult residents of Alcorcon (Spain) in the first wave of the disease up to April 25, 2020. RESULTS: The crude cumulative incidence among migrants (n=20,419) was higher than among Spaniards (n=131,599): 8.81 and 6.51 and per 1,000 inhabitants, respectively (p<.001), but differed by region of origin. As per a negative binomial regression adjusted for age and sex, relative risk (RR) for COVID-19 for individuals from Europe, Asia, or North Africa was not significantly different from Spaniards. In contrast, a markedly increased risk was found for people from Sub-Saharan Africa (RR 3.66, 95% confidence interval (CI) 1.42-9.41, p=.007), the Caribbean (RR 6.35, 95% CI 3.83-10.55, p<.001), and Latin America (RR 6.92, 95% CI 4.49-10.67, p<.001). CONCLUSIONS: Migrants from Sub-Saharan Africa, the Caribbean, and Latin America exhibited increased risk for COVID-19 as compared to Spaniards or migrants from Europe, North Africa, or Asia. Our data suggest that the ethnic background may play a role in risk for COVID-19. Migrants from some areas of the world may merit closer attention for both clinical and epidemiological reasons.

Outcomes of an enhanced recovery after radical cystectomy program in a prospective multicenter study: compliance and key components for success.

OBJECTIVE: To investigate the effect of an Enhanced Recovery After Surgery (ERAS) program on complications and length of stay (LOS) after radical cystectomy (RC) and to assess if the number and type of components of ERAS play a key role on the decrease of surgical morbidity. MATERIALS AND METHODS: We analyzed the data of 277 patients prospectively recruited in 11 hospitals undergoing RC initially managed according to local practice (Group I) and later within an ERAS program (Group II). Two main outcomes were defined: 90-day complications rate and LOS. As secondary variables we studied 90-day mortality, 30-day readmission and transfusion rate. RESULTS: Patients in Group II had a higher use of ERAS measures (98.6%) than those in Group I (78.2%) (p < 0.05). Patients in Groups I and II experienced similar complications (70.5% vs. 66%, p = 0.42). LOS was not different between Groups I and II (12.5 and 14 days, respectively, p = 0.59). The risk of having any complication decreases for patients having more than 15 ERAS measures adopted [RR = 0.815; 95% confidence interval (CI) 0.667-0.996; p = 0.045]. Avoidance of transfusion and nasogastric tube, prevention of ileus, early ambulation and a fast uptake of a regular diet are independently associated with the absence of complications. CONCLUSIONS: Complications and LOS after RC were not modified by the introduction of an ERAS program. We hypothesize that at least 15 measures should be applied to maximize the benefit of ERAS.

Transition from active surveillance to observation in prostate cancer patients older than 75 years. A long follow-up series. / Transición de vigilancia activa a observación en pacientes mayores de 75 años con cáncer de próstata en una serie de largo seguimiento.

INTRODUCTION: The world population is ageing, and life expectancy is increasing. This situation will have a great impact on the management of patients with prostate cancer, especially in those of low risk, susceptible to a conservative management under active surveillance (AS). Regarding these patients' profile, it is necessary to answer the following questions: ¿for how long to continue with the AS scheme?, ¿which tests will be required?, ¿is it possible to carry out a transition to observation with oncological safety? The objective of this work is to analyse those patients with prostatic cancer who have been in AS with 75 years of age or more and assess the safety of the observation in an AS series with a long follow-up. MATERIAL AND METHODS: We analysed our prospective cohort of AS patients between the years 1999 and 2018,including those who had been in follow-up with 75 years or more. They were offered treatment with curative intent when there were progression criteria and transition to observation under the urologist's decision. Some intermediate risk patients were included in the analysis. Comorbidity changes were analysed with the Charlson comorbidity index at entry and exit of AS. The progression and mortality of the patients were studied according to the management they received. RESULTS: From 347 AS patients, 90 patients fulfilled the afore mentioned criteria and 15 (16.7%) were intermediate risk. The median follow-up was 6.4 years and 73 (81.1%) had low comorbidity (Charlson<2).There were 40 (44.4%) patients who left AS, 17 (18.9%) of them went to observationand the rest, 21 (23.3%), received curative treatment. There was a significant difference in comorbidity, measured by the Charlson index, at entry and exit of AS (P<.05) among patients receiving active treatment and the ones submitted to observation.No case of cancer-specific death or progression was observed in the observation group. CONCLUSION: The transition from an active surveillance management to observation of prostate cancer elderly patients, as well as the decision to carry out a treatment with curative intent, seems controversial. In our series, this transition in patients older than 75 years does not increase the oncological risk.

Short-term association between outdoor air pollution and osteoporotic hip fracture.

This study examines the association of the levels of different airborne pollutants on the incidence of osteoporotic hip fracture in a southern European region. Association was detected between SO2 and NO2 and hospital admissions due to hip fracture. INTRODUCTION: To examine the short-term effects of outdoor air pollution on the incidence of osteoporotic hip fracture in a southern European region. METHODS: This is an ecological retrospective cohort study based on data obtained from three databases. In a time-series analysis, we examined the association between hip fracture incidence and different outdoor air pollutants (sulfur dioxide (SO2), monoxide (NO), nitrogen dioxide (NO2), ozone (O3), and particulate matter in suspension < 2.5 (PM2.5) and < 10-µm (PM10) conditions by using general additive models (Poisson distribution). The incidence rate ratio (IRR), crude and adjusted by season and different weather conditions, was estimated for all parameters. Hip incidence was later analyzed by sex and age (under or over age 75) subgroups. The main outcome measure was daily hospital admissions due to fracture. RESULTS: Hip fracture incidence showed association with SO2 (IRR 1.11 (95% CI 1.04-1.18)), NO (IRR 1.01 (95% CI 1.01-1.02)), and NO2 (IRR 1.02 (95% CI 1.01-1.04)). For O3 levels, this association was negative (IRR 0.97 (95% CI 0.95-0.99)). The association persisted for SO2 and NO2 when the models were adjusted by season. After adjusting by season and weather conditions, the association persisted for NO2. When participants were stratified by age and sex, associations persisted only in women older than 75 years. CONCLUSIONS: A short-term association was observed with several indicators of air pollution on hip fracture incidence. This is the first study that shows these associations.

Prognostic value of Ki-67 according to age in patients with triple-negative breast cancer.

PURPOSE: The prognostic value of Ki-67 in triple-negative breast cancer (TNBC) is yet unclear because the cut-off points employed differ widely and its predictive effect may vary according to age. The purpose of this study was to analyze the role of Ki-67 among patients with TNBC, and determine the optimal Ki-67 cut-off point to demonstrate its prognostic relevance associated with patient age and treatment strategy. METHODS/PATIENTS: 201 consecutive patients treated for primary TNBC from 1999 to 2014 were analyzed. Clinicopathological characteristics and outcomes were compared between patients treated with neoadjuvant or adjuvant chemotherapy. We used time-dependent receiver operating characteristic (ROC) curve and time-dependent area under the ROC curve (AUC) to evaluate the discriminative ability of Ki-67 at 3 and 5 years of follow-up. A Ki-67 cut-off point that maximized sensibility and specificity was established. Interaction effect between age and Ki-67 on disease-free survival (DFS) and overall survival (OS) was evaluated by stratified analysis. RESULTS: According to the coordinates of the ROC curves, the best cut-off point for Ki-67 was 60% (high/low). In the whole group, there was not a statistically significant association between Ki-67 and OS and DFS, using a cut-off point of 60%. In multivariate analysis (COX proportional hazards regression), for DFS high Ki-67 (> 60%) was a poor prognostic factor in patients > 40 years old and a better prognostic factor among the patients < 40 years old. CONCLUSION: Prognostic value of Ki-67 in TNBC, using a cut-off point of 60%, may vary depending on age.

Influence of the location and number of metastases in the survival of metastatic prostatic cancer patients. / Influencia de la localización y del número de metástasis en la supervivencia de los pacientes con cáncer de próstata metastásico.

INTRODUCTION: The prognosis of patients diagnosed with metastatic prostate cancer seems to be modulated by factors such as the number and site of metastases. Our objective is to evaluate survival outcomes according to the number and site of metastases in our series of metastatic patients over the last 15 years. MATERIALS AND METHODS: A retrospective analysis was performed on patients diagnosed between 1998 and 2014. We analyzed overall survival and progression-free survival, depending on the number and location of metastases on patients with newly diagnosed metastatic prostate cancer. Other potential prognostic factors were also evaluated: age, clinical stage, PSA at diagnosis, Gleason, PSA nadir, time till PSA nadir and first-line or second-line treatment after progression. RESULTS: We analyzed a series of 162 patients. The mean age was 72.7yr (SD: 8.5). The estimated median overall survival was 3.9 yr (95% CI 2.6-5.2). The overall survival in patients with only lymph node metastases was 7 yr (95% CI 4.1-9.7), 3.9 (95%CI 2.3-5.5) in patients with only bone metastases, 2.5 yr (95% CI 2-2.3) in lymph nodes and bone metastases, and 2.2 yr (95% CI 1.4-3) in patients with visceral metastases (P<.001). In multivariate analysis, the location of metastasesis significantly associated with overall survival and progression-free survival. The number of metastases showed no association with survival. CONCLUSIONS: The site of metastases has a clear impact on both overall survival and progression-free survival. Patients with only lymph node involvement had a better prognosis. The number of metastases showed no significant impact on survival in our series.

Variability in complications and operative mortality after radical cystectomy in Spain. / Variabilidad en las complicaciones y la mortalidad quirúrgica tras cistectomía radical en España.

BACKGROUND: In the literature, mortality for radical cystectomy (RC) varies between 2.3% and 7.5%. In Spain, there are no published general data on morbidity and mortality. OBJECTIVE: To identify the complications and mortality of RC in Spain through an analysis of all procedures performed over a 3-year period and to study the geographic variability of these results. MATERIAL AND METHODS: We identified patients who underwent RC in the Spanish National Health System between 2011 and 2013 based on the minimum basic data set. We analysed the complications and mortality during hospitalisation and at 30, 60 and 90 days. We compared these results in the various autonomous communities, adjusted them by age, Charlson score and sex and subsequently added the hospital size. RESULTS: We studied 7999 patients who underwent RC in 197 hospitals of the Spanish National Health System. The mean age of the series was 67.2±9.8 years. The median stay was 15 days (IQR, 11-24). Some 47.2% of the patients had complications. The mean mortality in-hospital and at 30, 60 and 90 days was 4.7, 2.9, 5 and 6.2%, respectively. There was considerable variability in the mortality at 90 days among the communities (3.8-9.1%). When adjusting by the patient and hospital characteristics, there were still significant geographic variations (3.8-11.5%). CONCLUSIONS: RC mortality in Spain at 90 days is similar to the rate in the literature. There are significant geographic variations unexplained by the characteristics of the patients or by those of the hospitals in which these operations were performed.