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Background: The association between heart rate (HR) and pulmonary embolism (PE) outcomes has not been well studied. Furthermore, optimal cutoffs to identify low-risk and intermediate- to high-risk patients are not well known. Research Question: Does an association exist between baseline HR and PE outcome across the continuum of HR values? Study Design and Methods: The current study included 44,331 consecutive nonhypotensive patients with symptomatic PE from the Registro Informatizado de la Enfermedad TromboEmbólica registry between 2001 and 2021. Outcomes included 30-day all-cause and PE-specific mortality. We used hierarchical logistic regression to assess the association between admission HR and outcomes. Results: A positive relationship was found between admission HR and 30-day all-cause and PE-related mortality. Considering an HR of 80 to 99 beats/min as a reference, patients in the higher HR strata showed higher rates of all-cause death (adjusted OR, 1.5 for HR of 100-109 beats/min; adjusted OR, 1.7 for HR of 110-119 beats/min; adjusted OR, 1.9 for HR of 120-139 beats/min; and adjusted OR, 2.4 for HR of ≥ 140 beats/min). Patients in the lower strata of HR showed significantly lower rates of 30-day all-cause mortality compared with the same reference group (adjusted OR, 0.6 for HR of 60-79 beats/min; and adjusted OR, 0.5 for HR of < 60 beats/min). The findings for 30-day PE-related mortality were similar. For identification of low-risk patients, a cutoff value of 80 beats/min (vs 110 beats/min) increased the sensitivity of the simplified Pulmonary Embolism Severity Index (sPESI) from 93.4% to 98.8%. For identification of intermediate- to high-risk patients, a cutoff value of 140 beats/min (vs 110 beats/min) increased the specificity of the Bova score from 93.2% to 98.0%. Interpretation: In nonhypotensive patients with acute symptomatic PE, a high HR portends an increased risk of all-cause and PE-related mortality. Modifying the HR cutoff in the sPESI and the Bova score improves prognostication of patients with PE.

We have updated recommendations on 12 controversial topics that were published in the 2013 National Consensus on the diagnosis, risk stratification and treatment of patients with pulmonary embolism (PE). A comprehensive review of the literature was performed for each topic, and each recommendation was evaluated in two teleconferences. For diagnosis, we recommend against using the Pulmonary Embolism Rule Out Criteria (PERC) rule as the only test to rule out PE, and we recommend using a D-dimer cutoff adjusted to age to rule out PE. We suggest using computed tomography pulmonary angiogram as the imaging test of choice for the majority of patients with suspected PE. We recommend using direct oral anticoagulants (over vitamin K antagonists) for the vast majority of patients with acute PE, and we suggest using anticoagulation for patients with isolated subsegmental PE. We recommend against inserting an inferior cava filter for the majority of patients with PE, and we recommend using full-dose systemic thrombolytic therapy for PE patients requiring reperfusion. The decision to stop anticoagulants at 3 months or to treat indefinitely mainly depends on the presence (or absence) and type of risk factor for venous thromboembolism, and we recommend against thrombophilia testing to decide duration of anticoagulation. Finally, we suggest against extensive screening for occult cancer in patients with PE.

Introduction Some local protocols suggest using intermediate or therapeutic doses of anticoagulants for thromboprophylaxis in hospitalized patients with coronavirus disease 2019 (COVID‐19). However, the incidence of bleeding, predictors of major bleeding, or the association between bleeding and mortality remain largely unknown. Methods We performed a cohort study of patients hospitalized for COVID‐19 that received intermediate or therapeutic doses of anticoagulants from March 25 to July 22, 2020, to identify those at increased risk for major bleeding. We used bivariate and multivariable logistic regression to explore the risk factors associated with major bleeding. Results During the study period, 1965 patients were enrolled. Of them, 1347 (69%) received intermediate‐ and 618 (31%) therapeutic‐dose anticoagulation, with a median duration of 12 days in both groups. During the hospital stay, 112 patients (5.7%) developed major bleeding and 132 (6.7%) had non‐major bleeding. The 30‐day all‐cause mortality rate for major bleeding was 45% (95% confidence interval [CI]: 36%‐54%) and for non‐major bleeding 32% (95% CI: 24%‐40%). Multivariable analysis showed increased risk for in‐hospital major bleeding associated with D‐dimer levels >10 times the upper normal range (hazard ratio [HR], 2.23; 95% CI, 1.38–3.59), ferritin levels >500 ng/ml (HR, 2.01; 95% CI, 1.02–3.95), critical illness (HR, 1.91; 95% CI, 1.14–3.18), and therapeutic‐intensity anticoagulation (HR, 1.43; 95% CI, 1.01–1.97). Conclusions Among patients hospitalized with COVID‐19 receiving intermediate‐ or therapeutic‐intensity anticoagulation, a major bleeding event occurred in 5.7%. Use of therapeutic‐intensity anticoagulation, critical illness, and elevated D‐dimer or ferritin levels at admission were associated with increased risk for major bleeding.

Background Eribulin’s clinical benefit remains unclear; so, studies analyzing its effectiveness in routine clinical practice are interesting. Patients and methods This is a multicenter, retrospective study including patients with human epidermal growth factor receptor-2-negative metastatic breast cancer which assesses effectiveness and safety of eribulin. Results A total of 140 women were included, with a median age of 57 years. The median overall survival and progression-free survival were 8.8 (95% confidence interval: 6.1–11.4) and 2.8 months (95% confidence interval: 2.5–3.1), respectively. For patients with hormonal receptor expression, a significantly longer progression-free survival was observed: 3.4 (95%confidence interval: 2.3–4.5) versus triple negative: 2.0 (95%confidence interval: 1.7–2.3) months, p = 0.003. Also, those who had received capecitabine prior to eribulin had a higher median overall survival than those who had not received it (9.5 months, 95% confidence interval: 6.6–12.5 vs. 4.8 months, 95% confidence interval: 3.4–6.2; p = 0.001). When only triple-negative patients were included, median overall survival was 6.5 (95% confidence interval: 0.1–16.2) for those who had received previous capecitabine versus 4.3 (95% confidence interval: 2.8–5.8) months for patients who had not received it; p =0.006. The safety profile of eribulin was adequate. Conclusion Effectiveness of eribulin in a real-life human epidermal growth factor receptor-2--negative population is lower than that observed in clinical trials. Its benefit seems to be higher in patients with hormonal receptor expression and patients who had received capecitabine prior to eribulin. The safety profile of eribulin is adequate.

The RIETE Investigators., [Background] The optimal therapy of patients with acute subsegmental pulmonary embolism (PE) is controversial., [Methods] We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to compare the rate of symptomatic PE recurrences during anticoagulation in patients with subsegmental, segmental, or more central PEs. [Results] Among 15 963 patients with a first episode of symptomatic PE, 834 (5.2%) had subsegmental PE, 3797 (24%) segmental, and 11 332 (71%) more central PE. Most patients in all subgroups received initial therapy with low‐molecular‐weight heparin, and then most switched to vitamin K antagonists. Median duration of therapy was 179, 185, and 204 days, respectively. During anticoagulation, 183 patients developed PE recurrences, 131 developed deep vein thrombosis (DVT), 543 bled, and 1718 died (fatal PE, 135). The rate of PE recurrences was twofold higher in patients with subsegmental PE than in those with segmental (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.16‐3.85) or more central PE (HR, 1.89; 95% CI, 1.12‐3.13). On multivariable analysis, patients with subsegmental PE had a higher risk for PE recurrences than those with central PE (adjusted HR, 1.75; 95% CI, 1.02‐3.03). After stratifying patients with subsegmental PE according to ultrasound imaging in the lower limbs, the rate of PE recurrences was similar in patients with DVT, in patients without DVT, and in those with no ultrasound imaging. [Conclusions] Our study reveals that the risk for PE recurrences in patients with segmental PE is not lower than in those with more central PE, thus suggesting that the risk of PE recurrences is not influenced by the anatomic location of PE.

INTRODUCTION Among the strategies designed to optimize the number of existing liver grafts for transplantation, the implementation of the graft assessment process is one of the least explored. The main objective is to identify the risk factors presented by liver donors for «NO validity». Secondly, we analyzed the coincidence between the surgeon's assessment and that of the anatomo-pathologist in the invalid donors. MATERIAL AND METHOD Retrospective study conducted from a prospective database that analyzes 190 liver donors, 95 valid and 95 NOT valid. The variables of each of them corresponding to the donation protocol of the National Transplant Organization are studied. Through a multivariate study we determine the independent risk factors of NO validity. We checked the causes of NO validity argued with the histopathological findings of these grafts. RESULTS The independent risk factors of non-validity in the multivariate study (P < .05) were: dyslipidemia, personal medical history other than cardiovascular and abdominal surgical risk factors, GGT, BrT, and the result of previous liver ultrasound. The 3 most frequent causes of NO validity were: steatosis, fibrosis and macroscopic appearance of the organ. 78% of the biopsies confirmed the NO validity of the graft (in 57.9% of the cases the histological findings coincided with those described by the surgeon). The 22.1% of the biopsies hadnt pathological findings. CONCLUSIONS The determination of the risk factors of NO validity will contribute to the design of future assessment scores that are useful tools in the process of liver graft assessment.).

Introduction Treatment of venous thromboembolism (VTE) in cancer patients with thrombocytopenia is challenging due to perceived higher risk of bleeding. Material and methods We used the RIETE registry to compare the 10- and 30-day outcomes in cancer patients with acute VTE, according to platelet count at baseline. Results As of December 2018, 15,337 cancer patients with VTE were included: 166 (1.1%) had Conclusions Cancer patients with acute VTE and baseline thrombocytopenia often receive initial lower-than recommended doses of LMWH. Although caution is required, this practice seems to be safe in patients with severe thrombocytopenia. Nonetheless, there was an inverse correlation between baseline platelet count and mortality.

Edoxaban is used for venous thromboembolism (VTE) treatment. Real-life data are lacking about its use in long-term therapy. We aimed to assess the efficacy and the safety of edoxaban for long-term VTE treatment in a real-life setting. Patients with VTE included in the Registro Informatizado Enfermedad TromboEmbólica (RIETE) registry, receiving edoxaban 60 or 30 mg daily were prospectively followed up to validate the benefit of using different dosages. The main outcome was the composite of VTE recurrences or major bleeding in patients with or without criteria for dose reduction. Multivariable analysis to identify predictors for the composite outcome was performed. From October 2015 to November 2019, 562 patients received edoxaban for long-term therapy. Most (94%) of the 416 patients not meeting criteria for dose reduction received 60 mg daily, and 92 patients meeting criteria (63%) received 30 mg daily. During treatment, two patients developed recurrent VTE, six had major bleeding and nine died (2 from fatal bleeding). Among patients not meeting criteria for dose reduction, those receiving 30 mg daily had a higher rate of the composite event (hazard ratio (HR) 8.37; 95% confidence interval (CI) 1.12–42.4) and a significant higher mortality rate (HR 31.1; 95% CI 4.63–262) than those receiving 60 mg. Among patients meeting criteria for dose reduction, those receiving 60 mg daily had no events, and a nonsignificantly higher mortality rate (HR 5.04; 95% CI 0.54–133) than those receiving 30 mg daily. In conclusion, edoxaban seems to be effective and safe for long-term VTE treatment in real life. Criteria for dose reduction should be reformulated., No funding was received for this work

[Background] The length of hospital stay (LOS) for acute pulmonary embolism (PE) varies considerably. Whether the upfront use of a PE prognostic assessment and management pathway is effective in reducing the LOS remains unknown., [Methods] We conducted a randomised controlled trial of adults hospitalised for acute PE: patients were assigned either to a prognostic assessment and management pathway involving risk stratification followed by predefined criteria for mobilisation and discharge (intervention group) or to usual care (control group). The primary end-point was LOS. The secondary end-points were the cost of prognostic tests and of hospitalisation, and 30-day clinical outcomes., [Results] Of 500 patients who underwent randomisation, 498 were included in the modified intention-to-treat analysis. The median LOS was 4.0 days (interquartile range (IQR) 3.7–4.2 days) in the intervention group and 6.1 days (IQR 5.7–6.5 days) in the control group (p, [Conclusions] The use of a prognostic assessment and management pathway was effective in reducing the LOS for acute PE.

[Objectives] We evaluated the association of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) rectal colonisation with crude mortality and whether this association is independent of the risk of KPC-Kp infection., [Methods] This was a prospective cohort study of patients followed-up 90 days after a study of rectal colonisation. Cox regression was used to study the variables associated with crude mortality. Sensitivity analyses for 90-day crude mortality in different subcohorts were performed., [Results] A total of 1244 patients (1078 non-colonised and 166 colonised) were included. None of the non-colonised patients and 78 (47.0%) of the colonised patients developed KPC-Kp infection. The 90-day crude mortality was 18.0% (194/1078) in non-colonised patients and 41.6% (69/166) in colonised patients. Rectal colonisation was not associated with crude mortality [hazard ratio (HR) = 1.03, 95% confidence interval (CI) 0.69–1.54; P = 0.85] when the model was adjusted for severe KPC-Kp infection [INCREMENT-CPE score (ICS) > 7]. KPC-Kp infection with ICS > 7 was associated with an increased risk of all-cause mortality (HR = 2.21, 95% CI 1.35–3.63; P = 0.002). In the sensitivity analyses, KPC-Kp colonisation was not associated with mortality in any of the analysed subcohorts, including patients who did not develop KPC-Kp infection (HR = 0.93, 95% CI 0.60–1.43; P = 0.74)., [Conclusion] KPC-Kp rectal colonisation was not associated with crude mortality. Mortality increased when colonised patients developed severe KPC-Kp infection (ICS > 7). Rectal colonisation was a necessary although insufficient condition to die from a KPC-Kp infection., This work was supported by the Spanish National R&D&I Plan 2013–2016 and the Carlos III Health Institute (ISCIII), Sub-Directorate General for Cooperative Research Networks and Centers, Spanish Ministry of Economy, Industry and Competitiveness, Spanish Network for Research in Infectious Diseases [REIPI RD16/0016/0001; RD16/0016/0008] and co-financed by the European Regional Development Fund ‘A Way to Achieve Europe’, Operative Program Intelligent Growth 2014–2020.

Importance: Understanding the impact of endometriosis symptoms on patients’ activities of daily living (ADLs) is a priority to establish effective and personalized intervention programs. Objective: To explore limitations in ADLs and instrumental ADLs (IADLs) and their association with pelvic pain (PP), chronic fatigue, and pain-catastrophizing thoughts among women with endometriosis. Design: Cross-sectional study. Setting: Spain. Participants: Two hundred thirty women with endometriosis. Outcomes and Measures: Information regarding performance of ADLs (Barthel Index) and IADLs (Lawton–Brody questionnaire), PP intensity (Numeric Rating Scale), chronic fatigue (Piper Fatigue Scale), and pain-catastrophizing thoughts (Pain Catastrophizing Scale) was gathered. Multivariate regression analyses were created, and mediating effects of fatigue and pain-catastrophizing thoughts on the association between PP and ADL and IADL limitations were assessed. Results: The prevalence of limitations in at least one ADL and one IADL was 22.6% (95% confidence interval [CI] [17.2, 28.1]) and 39.1% (95% CI [32.8, 45.5]), respectively. Limitations in bowel continence, housework, shopping, and meal preparation were reported most frequently. Women reporting severe PP showed higher risk for ADL (odds ratio [OR] = 3.33, 95% CI [1.10, 10.10]) and IADL (OR = 7.99, 95% CI [2.86, 22.34]) limitations. Chronic fatigue and pain-catastrophizing thoughts were also positively related to ADL–IADL limitations, showing a mediating effect on the association between PP and ADL–IADL limitations. Conclusions and Relevance: This study reveals the widespread presence of difficulties in ADL–IADL performance among women with endometriosis, with some symptoms underlying these difficulties in occupational performance. This study points to the need for cost-effective occupational therapy interventions for affected women. What This Article Adds: This research shows that the occupational performance of women with endometriosis is frequently impaired; therefore, the effectiveness of occupational therapy interventions should be addressed in the near future.

The association between elevated liver enzymes or FIB-4 (fibrosis index 4) and outcome in patients with venous thromboembolism (VTE) has not been evaluated. Data from patients in RIETE (Registro Informatizado Enfermedad TromboEmbólica) were used to assess the association between elevated liver enzymes or FIB-4 levels and the rates of major bleeding or death in apparent liver disease-free patients with acute VTE under anticoagulation therapy. A total of 6206 patients with acute VTE and without liver disease were included. Of them, 92 patients had major bleeding and 168 died under anticoagulation therapy. On multivariable analysis, patients with elevated liver enzymes were at increased mortality risk (HR: 1.58; 95% CI: 1.10–2.28), while those with FIB-4 levels > 2.67 points were at increased risk for major bleeding (HR: 1.69; 95% CI: 1.04–2.74). Evaluation of liver enzymes and FIB-4 index at baseline in liver disease-free patients with VTE may provide additional information on the risk for major bleeding or death during anticoagulation. Supplementary Information The online version contains supplementary material available at 10.1007/s11739-021-02858-x.

The authors would like to extend their gratitude and acknowledgments to all study participants and to all Foundations, Institutions, and Societies that supported the survey, helping in the process of dissemination: Asociacion Colombiana de Dietistas y Nutricionistas, ACODIN, Asociacion Colombiana de Facultades de Nutricion y Dietetica (ACOFANUD), Asociacion de Egresados de Nutricion y Dietetica de la Universidad Nacional (ANDUN), Colegio colombiano de nutricionistas Dietistas-COLNUD, Observatorio de Soberania y Seguridad alimentaria y Nutricional de la Universidad Nacional de Colombia (OBSSAN UN). The authors are also thankful to Gloria Esperanza Prada Gomez from Universidad Industrial de Santander (Facultad de Salud, Escuela de Nutricion y Dietetica), who also supported the dissemination of the survey in the Eastern region of Colombia. Sonia Liliana Pertuz Cruz is thankful to Fundacion Carolina, for a doctoral scholarship award., The aim of this study was to evaluate the impact of coronavirus SARS-Cov2 (COVID-19) confinement measures in Colombia on the dietary behaviors of a large population sample, at national and regional levels. A survey was conducted to assess dietary behaviors during the COVID-19 confinement. The survey involved 2,745 participants, aged 18 years or older, from six regions of the country (Atlantica, Bogota, Central, Oriental, Orinoquia and Amazonia, and Pacifica). Dietary intake of foods and foods groups in grams per day before and during the confinement was estimated by considering standard serving sizes of foods. One-way ANOVA was used to analyze differences between the regions with regard to dietary behavior changes during the confinement. Differences were deemed significant at p-value < 0.05. Dietary patterns (DPs) before and during the confinement were derived from principal component analysis. Certain dietary habits were adopted by the study population during the confinement (e.g., higher frequency of snacking and home cooking), with significant differences by regions with regard to these habits, as well as regarding culinary processes. The levels of consumption of several foods also changed during the confinement, nationally and regionally. We identified three DPs before the confinement (protein-rich, carbohydrate-rich, and sugar foods patterns) and four DPs during the confinement (westernized, carbohydrate-rich, protein-rich, fish and fruits-vegetable patterns), with an explained total variance of 33 and 45%, respectively. The profile of these DPs varied to some extent between the regions; their adherence to each DP also varied (p-value < 0.001). Our results show that there were marked differences by regions in the dietary behaviors of this population during the confinement, with an overall trend toward unhealthier DPs. These results may help to shape public health nutrition interventions in Colombia during the COVID-19 pandemic and in a post-COVID stage., Fundacion Carolina, Asociacion Colombiana de Dietistas y Nutricionistas, ACODIN, Asociacion Colombiana de Facultades de Nutricion y Dietetica (ACOFANUD), Asociacion de Egresados de Nutricion y Dietetica de la Universidad Nacional (ANDUN), Colegio colombiano de nutricionistas Dietistas-COLNUD, Observatorio de Soberania y Seguridad alimentaria y Nutricional de la Universidad Nacional de Colombia (OBSSAN UN)

Aims Little is known about the prognosis of patients with massive pulmonary embolism (PE) and its risk of recurrent venous thromboembolism (VTE) compared with non-massive PE, which may inform clinical decisions. Our aim was to compare the risk of recurrent VTE, bleeding, and mortality after massive and non-massive PE during anticoagulation and after its discontinuation. Methods and results We included all participants in the RIETE registry who suffered a symptomatic, objectively confirmed segmental or more central PE. Massive PE was defined by a systolic hypotension at clinical presentation (

Tau neurofibrillary tangle (NFT) pathology in the medial temporal lobe (MTL) is closely linked to neurodegeneration, and is the early pathological change associated with Alzheimer’s disease (AD). To elucidate patterns of structural change in the MTL specifically associated with tau pathology, we compared high-resolution ex vivo MRI scans of human postmortem MTL specimens with histology-based pathological assessments of the MTL. MTL specimens were obtained from twenty-nine brain donors, including patients with AD, other dementias, and individuals with no known history of neurological disease. Ex vivo MRI scans were combined using a customized groupwise diffeomorphic registration approach to construct a 3D probabilistic atlas that captures the anatomical variability of the MTL. Using serial histology imaging in eleven specimens, we labelled the MTL subregions in the atlas based on cytoarchitecture. Leveraging the atlas and neuropathological ratings of tau and TAR DNA-binding protein 43 (TDP-43) pathology severity, morphometric analysis was performed to correlate regional MTL thickness with the severity of tau pathology, after correcting for age and TDP-43 pathology. We found significant correlations between tau pathology and thickness in the entorhinal cortex (ERC) and stratum radiatum lacunosum moleculare (SRLM). When focusing on cases with low levels of TDP-43 pathology, we found strong associations between tau pathology and thickness in the ERC, SRLM and the subiculum/cornu ammonis 1 (CA1) subfields of the hippocampus, consistent with early Braak stages. Supplementary Information The online version contains supplementary material available at 10.1186/s40478-021-01275-7.

Thromboprophylaxis with low molecular weight heparin in hospitalized patients with COVID-19 is mandatory, unless contraindicated. Given the links between inflammation and thrombosis, the use of higher doses of anticoagulants could improve outcomes. We conducted an open-label, multicenter, randomized, controlled trial in adult patients hospitalized with nonsevere COVID-19 pneumonia and elevated D-dimer. Patients were randomized to therapeutic-dose bemiparin (115 IU/kg daily) versus standard prophylaxis (bemiparin 3,500 IU daily), for 10 days. The primary efficacy outcome was a composite of death, intensive care unit admission, need of mechanical ventilation support, development of moderate/severe acute respiratory distress, and venous or arterial thrombosis within 10 days of enrollment. The primary safety outcome was major bleeding (International Society on Thrombosis and Haemostasis criteria). A prespecified interim analysis was performed when 40% of the planned study population was reached. From October 2020 to May 2021, 70 patients were randomized at 5 sites and 65 were included in the primary analysis; 32 patients allocated to therapeutic dose and 33 to standard prophylactic dose. The primary efficacy outcome occurred in 7 patients (22%) in the therapeutic-dose group and 6 patients (18%) in the prophylactic-dose (absolute risk difference 3.6% [95% confidence interval [CI], –16% –24%]; odds ratio 1.26 [95% CI, 0.37–4.26]; p = 0.95). Discharge in the first 10 days was possible in 66 and 79% of patients, respectively. No major bleeding event was registered. Therefore, in patients with COVID-19 hospitalized with nonsevere pneumonia but elevated D-dimer, the use of a short course of therapeutic-dose bemiparin does not appear to improve clinical outcomes compared with standard prophylactic doses. Trial Registration: ClinicalTrials.gov NCT04604327.

SLICE Trial Group., [Importance] Active search for pulmonary embolism (PE) may improve outcomes in patients hospitalized for exacerbations of chronic obstructive pulmonary disease (COPD)., [Objective] To compare usual care plus an active strategy for diagnosing PE with usual care alone in patients hospitalized for COPD exacerbation., [Design, Setting, and Participants] Randomized clinical trial conducted across 18 hospitals in Spain. A total of 746 patients were randomized from September 2014 to July 2020 (final follow-up was November 2020)., [Interventions] Usual care plus an active strategy for diagnosing PE (D-dimer testing and, if positive, computed tomography pulmonary angiogram) (n = 370) vs usual care (n = 367)., [Main Outcomes and Measures] The primary outcome was a composite of nonfatal symptomatic venous thromboembolism (VTE), readmission for COPD, or death within 90 days after randomization. There were 4 secondary outcomes, including nonfatal new or recurrent VTE, readmission for COPD, and death from any cause within 90 days. Adverse events were also collected., [Results] Among the 746 patients who were randomized, 737 (98.8%) completed the trial (mean age, 70 years; 195 [26%] women). The primary outcome occurred in 110 patients (29.7%) in the intervention group and 107 patients (29.2%) in the control group (absolute risk difference, 0.5% [95% CI, −6.2% to 7.3%]; relative risk, 1.02 [95% CI, 0.82-1.28]; P = .86). Nonfatal new or recurrent VTE was not significantly different in the 2 groups (0.5% vs 2.5%; risk difference, −2.0% [95% CI, −4.3% to 0.1%]). By day 90, a total of 94 patients (25.4%) in the intervention group and 84 (22.9%) in the control group had been readmitted for exacerbation of COPD (risk difference, 2.5% [95% CI, −3.9% to 8.9%]). Death from any cause occurred in 23 patients (6.2%) in the intervention group and 29 (7.9%) in the control group (risk difference, −1.7% [95% CI, −5.7% to 2.3%]). Major bleeding occurred in 3 patients (0.8%) in the intervention group and 3 patients (0.8%) in the control group (risk difference, 0% [95% CI, −1.9% to 1.8%]; P = .99)., [Conclusions and Relevance] Among patients hospitalized for an exacerbation of COPD, the addition of an active strategy for the diagnosis of PE to usual care, compared with usual care alone, did not significantly improve a composite health outcome. The study may not have had adequate power to assess individual components of the composite outcome., [Trial Registration] ClinicalTrials.gov Identifier: NCT02238639.

Background Bleeding risk is highly relevant for treatment decisions in cancer-associated thrombosis (CAT). Several risk scores exist, but have never been validated in patients with CAT and are not recommended for practice. Objectives To compare methods of estimating clinically relevant (major and clinically relevant nonmajor) bleeding risk in patients with CAT: (1) existing risk scores for bleeding in venous thromboembolism, (2) pragmatic classification based on cancer type, and (3) new prediction model. Methods In a posthoc analysis of the Hokusai VTE Cancer study, a randomized trial comparing edoxaban with dalteparin for treatment of CAT, seven bleeding risk scores were externally validated (ACCP-VTE, HAS-BLED, Hokusai, Kuijer, Martinez, RIETE, and VTE-BLEED). The predictive performance of these scores was compared with a pragmatic classification based on cancer type (gastrointestinal; genitourinary; other) and a newly derived competing risk-adjusted prediction model based on clinical predictors for clinically relevant bleeding within 6 months after CAT diagnosis with nonbleeding-related mortality as the competing event (“CAT-BLEED”). Results Data of 1,046 patients (149 events) were analyzed. Predictive performance of existing risk scores was poor to moderate (C-statistics: 0.50–0.57; poor calibration). Internal validation of the pragmatic classification and “CAT-BLEED” showed moderate performance (respective C-statistics: 0.61; 95% confidence interval [CI]: 0.56–0.66, and 0.63; 95% CI 0.58–0.68; good calibration). Conclusion Existing risk scores for bleeding perform poorly after CAT. Pragmatic classification based on cancer type provides marginally better estimates of clinically relevant bleeding risk. Further improvement may be achieved with “CAT-BLEED,” but this requires external validation in practice-based settings and with other DOACs and its clinical usefulness is yet to be demonstrated.

Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90‐day and 1‐year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90‐day all‐cause (odds ratio [OR], 2.81; 95% CI, 2.33–3.38) and PE‐related mortality (OR, 2.38; 95% CI, 1.37–4.14) and increased 1‐year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10–9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all‐cause mortality (OR, 1.91; 95% CI, 1.57–2.32) but not PE‐related mortality (OR, 1.50; 95% CI, 0.85–2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90‐day all‐cause (OR, 2.28; 95% CI, 1.75–2.97) and PE‐related (OR, 3.64; 95% CI, 2.01–6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.

Registro Informatizado de Enfermedad Tromboembólica Investigators., [Objective] Overlap exists between the risk factors for coronary artery disease and venous thromboembolism (VTE). However, a paucity of data is available on the incidence of major acute cardiovascular events (MACE) and major adverse limb events (MALE) among patients presenting with VTE. Moreover, it is unknown whether the rate of cardiovascular outcomes differs among patients with unprovoked vs provoked VTE., [Methods] We analyzed the data from 2009 to 2017 in the Registro Informatizado de Enfermedad Tromboembólica registry, an ongoing, multicenter, international registry of consecutive patients with a diagnosis of objectively confirmed VTE. The query was restricted it to patients with data entry for the arterial outcomes. The baseline prevalence of coronary artery disease risk factors was compared between patients with provoked (ie, immobility, cancer, surgery, travel >6 hours, hormonal causes) and unprovoked VTE. After the initial VTE event, we followed up patients for the composite primary outcome of incident MACE (ie, stroke, myocardial infarction, unstable angina) and/or MALE (ie, major limb events). We used the χ2 test for baseline associations and a Cox proportional hazard for multivariate analysis. We used IBM SPSS, version 24 (IBM Corp, Armonk, NY) for statistical analysis. A P value of, [Results] We analyzed the data from 41,259 patients with VTE, of whom 22,633 (55.6%) had experienced a provoked VTE. During follow-up, the patients with provoked VTE were more likely to develop MACE or MALE than were patients with unprovoked VTE (hazard ratio [HR], 1.3; 95% confidence interval [CI], 1.1-1.5). The association of arterial events with recent immobility (HR, 1.4; 95% CI, 1.5-12.1) and cancer (HR, 1.7; 95% CI, 1.4-1.9) was strong. After adjusting for multiple conventional cardiovascular risk factors, provoked VTE, compared with unprovoked VTE, was significantly associated with an increased hazard for MACE (HR, 1.4; 95% CI, 1.1-1.7). Cancer remained a significant adjusted predictor for both MACE (HR, 1.7; 95% CI, 1.4-2.1) and MALE (HR, 2.1; 95% CI 1.01-4.6) in those with provoked VTE., [Conclusions] Among patients with VTE, provoked cases, specifically those with cancer-associated VTE, have an increased risk of major arterial events.

Background Patients with venous thromboembolism (VTE) secondary to transient risk factors may develop VTE recurrences after discontinuing anticoagulation. Identifying at‐risk patients could help to guide the duration of therapy. Methods We used the RIETE database to assess the prognostic value of d‐dimer testing after discontinuing anticoagulation to identify patients at increased risk for recurrences. Transient risk factors were classified as major (postoperative) or minor (pregnancy, oestrogen use, immobilization or recent travel). Results In December 2018, 1655 VTE patients with transient risk factors (major 460, minor 1195) underwent d‐dimer measurements after discontinuing anticoagulation. Amongst patients with major risk factors, the recurrence rate was 5.74 (95% CI: 3.19–9.57) events per 100 patient‐years in those with raised d‐dimer levels and 2.68 (95% CI: 1.45–4.56) in those with normal levels. Amongst patients with minor risk factors, the rates were 7.79 (95% CI: 5.71–10.4) and 3.34 (95% CI: 2.39–4.53), respectively. Patients with major risk factors and raised d‐dimer levels (n = 171) had a nonsignificantly higher rate of recurrences (hazard ratio [HR]: 2.14; 95% CI: 0.96–4.79) than those with normal levels. Patients with minor risk factors and raised d‐dimer levels (n = 382) had a higher rate of recurrences (HR: 2.34; 95% CI: 1.51–3.63) than those with normal levels. On multivariate analysis, raised d‐dimers (HR: 1.74; 95% CI: 1.09–2.77) were associated with an increased risk for recurrences in patients with minor risk factors, not in those with major risk factors. Conclusions Patients with raised d‐dimer levels after discontinuing anticoagulant therapy for VTE provoked by a minor transient risk factor were at an increased risk for recurrences. Sin financiación 8.989 JCR (2020) Q1, 12/167 Medicine, General & Internal 2.625 SJR (2020) Q1, 9/131 Internal Medicine No data IDR 2020 UEM

The RIETE investigators., In young patients with acute pulmonary embolism (PE), the predictive value of currently available prognostic tools has not been evaluated. Our objective was to compare prognostic value of 7 available tools (GPS, PESI, sPESI, Prognostic Algorithm, PREP, shock index and RIETE) in patients aged, This study received funding: SEPAR (1/2016) grupo GeCIR. We express our gratitude to Sanofi Spain for supporting this Registry with an unrestricted educational grant. We also wish to thank Bayer Pharma AG for supporting this Registry. Bayer Pharma AG’s support was limited to the part of RIETE outside Spain, which accounts for a 25.20% of the total patients included in the RIETE Registry.

The medial temporal lobe (MTL) is a nidus for neurodegenerative pathologies and therefore an important region in which to study polypathology. We investigated associations between neurodegenerative pathologies and the thickness of different MTL subregions measured using high-resolution post-mortem MRI. Tau, TAR DNA-binding protein 43 (TDP-43), amyloid-β and α-synuclein pathology were rated on a scale of 0 (absent)—3 (severe) in the hippocampus and entorhinal cortex (ERC) of 58 individuals with and without neurodegenerative diseases (median age 75.0 years, 60.3% male). Thickness measurements in ERC, Brodmann Area (BA) 35 and 36, parahippocampal cortex, subiculum, cornu ammonis (CA)1 and the stratum radiatum lacunosum moleculare (SRLM) were derived from 0.2 × 0.2 × 0.2 mm3 post-mortem MRI scans of excised MTL specimens from the contralateral hemisphere using a semi-automated approach. Spearman’s rank correlations were performed between neurodegenerative pathologies and thickness, correcting for age, sex and hemisphere, including all four proteinopathies in the model. We found significant associations of (1) TDP-43 with thickness in all subregions (r = − 0.27 to r = − 0.46), and (2) tau with BA35 (r = − 0.31) and SRLM thickness (r = − 0.33). In amyloid-β and TDP-43 negative cases, we found strong significant associations of tau with ERC (r = − 0.40), BA35 (r = − 0.55), subiculum (r = − 0.42) and CA1 thickness (r = − 0.47). This unique dataset shows widespread MTL atrophy in relation to TDP-43 pathology and atrophy in regions affected early in Braak stageing and tau pathology. Moreover, the strong association of tau with thickness in early Braak regions in the absence of amyloid-β suggests a role of Primary Age-Related Tauopathy in neurodegeneration. Supplementary Information The online version contains supplementary material available at 10.1186/s40478-021-01225-3.

EnglishObjective. Main objective was whether the combination of C-Reactive Protein (CRP) and Alvarado Score (AS) increase the diagnosis accuracy of AS among 2-to-20-year-old patients with suspected acute appendicitis presenting to Emergency Departments. Materials and methods. This is a secondary analysis of prospective cohort study consecutively including all patients from 2 to 20 years of age attended for suspected acute appendicitis in 4 Spanish Emergency Departments during 6-month period. We collected demographic, clinical, analytic and radiographic, and surgical data. AS categories were retrospectively calculated as low (0-4 points), intermediate (5-6 points) or high (7-10 points). The cut-off levels were >0.5 mg/dl for CRP. The outcome was diagnosis of acute appendicitis within 14 days of the index visit. Results. A total of 331 patients with suspected of acute appendicitis (mean age 11.8 (SD 3.8) years; 52.9% males) were recruited. According to AS, 108 (32.6%) were at low risk, 76 at (23.0%) intermediate risk and 147 (44.4%) at high risk of acute appendicitis. One hundred and sixteen (35.0%) cases had confirmed histopathological diagnosis of acute appendicitis. The AUCs of ROC were 0.76 (0.70-0.81) for AS and 0.79 (95% CI 0.75-0.84) for CRP-AS being the difference statistically significant (p=0.003). The CRP for diagnosis acute appendicitis in low risk AS group had negative predictive value of 95.8% (95%CI 87.3-98.9) and likelihood ratio negative of 0.4 (95%CI 0.2-1.0). Conclusions. CRP-AS has shown to increase the diagnostic accuracy of AS for acute appendicitis. This approach may be useful to rule out the diagnosis of acute appendicitis in paediatric patients attended for abdominal pain suggestive of acute appendicitis. EnglishObjetivo. El objetivo principal fue conocer si la combinacion de la proteina C reactiva (PCR) y la escala de Alvarado (AS) aumenta la precision de esta ultima en el diagnostico de apendicitis aguda en pacientes de 2 a 20 anos que son evaluados en los servicios de urgencias hospitalarios con esta sospecha clinica. Materiales y metodos. Se trata de un analisis secundario de un estudio de cohorte prospectivo que incluyo de forma consecutiva a todos los pacientes de 2 a 20 anos atendidos por sospecha de apendicitis aguda en 4 servicios de urgencias hospitalarios espanoles durante un periodo de 6 meses. Recopilamos datos demograficos, clinicos, analiticos, radiograficos

Background Liver retransplantation can be classified as urgent (when performed in the first week after the transplantation) or elective, which may be considered as early (first month post-transplantation) or late (after the first month). The time in which retransplantation takes place is determined by the cause that makes it necessary. The goal of this study is to analyze the causes and results of early retransplantation in our center. Methods A retrospective analysis of liver retransplantations performed within the first month after the original transplantation in our center between 2007 and 2017 was carried out. The variables analyzed were demographic, causes of the first transplant and retransplantation, and the complications and mortality resulting from the latter. Results A total of 698 liver transplants were performed, including 67 patients who required retransplantation (8.9%). Among these, 37 were late elective retransplantations and 30 were early retransplantations. Regarding the latter, the causes that led to the first transplant were hepatocellular carcinoma (46.7%) and noncholestatic cirrhosis (30%). On the other hand, the main precipitants of the retransplantation were hepatic artery thrombosis (60%) and primary graft failure (13.3%). The reoperation rate was 16.7%, and the perioperative mortality rate was 16.7%. The 1-, 2-, and 5-year survival rates were 83.3%, 76.7% and 59.9%, respectively. Conclusion Despite the high perioperative morbidity of liver retransplantation, its results in terms of survival are similar to those of the global series of liver transplantation.

Colorectal cancer (CRC) has the second-highest tumor incidence and is a leading cause of death by cancer. Nearly 20% of patients with CRC will have metastases at the time of diagnosis, and more than 50% of patients with CRC develop metastatic disease during the course of their disease. A group of experts from the Spanish Society of Medical Oncology, the Spanish Association of Surgeons, the Spanish Society of Radiation Oncology, the Spanish Society of Vascular and Interventional Radiology, and the Spanish Society of Nuclear Medicine and Molecular Imaging met to discuss and provide a multidisciplinary consensus on the management of liver metastases in patients with CRC. The group defined the different scenarios in which the disease can present: fit or unfit patients with resectable liver metastases, patients with potential resectable liver metastases, and patients with unresectable liver metastases. Within each scenario, the different strategies and therapeutic approaches are discussed.

BACKGROUND Sarcopenia is an important health problem in older adults. The aim was to study the association of anthropometric measurements, functional capacity, cognitive impairment, and nutrition status with sarcopenia in institutionalized older adults. METHODS A cross-sectional study was undertaken, determining the calf circumference (CC), mid-upper arm muscle circumference (MUAMC), and body mass index (BMI) and administering the Pfeiffer test and Mini Nutritional Assessment Short Form (MNA-SF). Sarcopenia was diagnosed following criteria of the European Working Group on Sarcopenia in Older People. After bivariate analyses, a multivariate logistic regression model was constructed to determine the association of study variables with sarcopenia. RESULTS The study group comprised 249 residents (mean age 84.9 ± 6.7 years). The prevalence of sarcopenia was 63%. The multivariate analysis with adjusted odds ratios (ORs) indicated that the risk of sarcopenia was significantly increased by being female (OR = 2.8; 95% CI 1.3-6.2), having moderate or severe cognitive impairment (Pfeiffer test score of 5-10) (OR = 2.4; 95% CI 0.9-6.4), and having a BMI < 22 kg/m2 (OR = 22.4; 95% CI 6.7-75.0). Moreover, a low CC (OR = 6.5; 95% CI 3.0-14.0) or MUAMC (OR = 3.9; 95% CI 1.7-9.3) also significantly increased the risk of sarcopenia. A negative association was observed between sarcopenia and MNA-SF, although it did not remain statistically significant in the multivariate analysis. CONCLUSIONS The variables identified as risk factors for sarcopenia can assist in detecting individuals at higher risk who require special clinical attention.

Background: Little is known about the prevalence and impact of risk of malnutrition on short-term mortality among seniors presenting with acute heart failure (AHF) in emergency setting. The objective was to determine the impact of risk of malnutrition on 30-day mortality risk among older patients who attended in Emergency Departments (EDs) for AHF. Material and methods: We performed a secondary analysis of the OAK-3 Registry including all consecutive patients >= 65 years attending in 16 Spanish EDs for AHF. Risk of malnutrition was defined by the Mini Nutritional Assessment Short Form (MNA-SF) < 12 points. Unadjusted and adjusted logistic regression models were used to assess the association between risk of malnutrition and 30-day mortality. Results: We included 749 patients (mean age: 85 (SD 6); 55.8% females). Risk of malnutrition was observed in 594 (79.3%) patients. The rate of 30-day mortality was 8.8%. After adjusting for MEESSI-AHF risk score clinical categories (model 1) and after adding all variables showing a significantly different distribution among groups (model 2), the risk of malnutrition was an independent factor associated with 30-day mortality (adjusted OR by model 1 = 3.4; 95% CI 1.2-9.7; p = .020 and adjusted OR by model 2 = 3.1; 95% CI 1.1-9.0; p = .033) compared to normal nutritional status. Conclusions: The risk of malnutrition assessed by the MNA-SF is associated with 30-day mortality in older patients with AHF who were attended in EDs. Routine screening of risk of malnutrition may help emergency physicians in decision-making and establishing a care plan.

Background Immunotherapy has become a standard treatment for lung cancer; however, the high cost makes it necessary to assess health outcomes. Objective The aim of this study was to evaluate the effectiveness, safety and economic cost of nivolumab in real-world clinical practice. Setting Fifteen regional and academic hospitals from Spain participated in this study. Methods This study was a retrospective, multicentre and observational study involving patients who experienced progression after first-line therapy for non-small-cell lung cancer and were treated with nivolumab between January 2016 and July 2017. Effectiveness and safety were evaluated by the oncologist, and the data from the electronic clinical records of the patients were collected by the research team. Economic cost was calculated using the cost of acquiring nivolumab for the public health system. Main outcome measures Effectiveness variables were overall survival (OS) and progression-free survival (PFS). The safety variable was the incidence of adverse events (AEs), and the cost per life-year gained (LYG) was the economic variable. Results A total of 221 patients were enrolled (83.7% men). The mean age was 64.5 years, and 84.6% of the patients had an Eastern Cooperative Oncology Group (ECOG) performance-status score of 0–1. Squamous tumours accounted for 59.7% of the total, and 78.7% of the patients presented a time since platinum therapy (TPT) > 6 months. The mean nivolumab dose was 216 mg (SD 211), and the treatment duration was 7.0 months (95% CI 5.8–8.1). The median PFS was 5.3 months (95% CI 3.2–7.3), and OS was 9.7 months (95% CI 7.6–11.8). The median PFS and OS values were statistically significantly superior for patients with an ECOG score of 0–1 and for patients with a TPT > 6 months. The median OS was also statistically significantly superior for patients with non-squamous histology. Regarding safety, 71% of the patients presented AEs of any grade, and in 18.6%, the nivolumab treatment had to be delayed or discontinued. The cost of nivolumab per patient was €19,910.00 (SD 19,369), and the cost per LYG was €110,026.00 (€77,557.00–€231,171.00). Conclusions This study confirms that the efficacy and safety of nivolumab treatment in a real population are comparable to the results obtained in clinical trials. A greater clinical benefit of nivolumab therapy was observed in patients with an ECOG score of 0–1, a TPT > 6 months or non-squamous histology. Despite the benefit observed, the cost per LYG is above the threshold of efficiency established by public health institutes.

Objective To assess the importance of intraoperative portal vein flow measurement during liver transplantation in relation to postoperative complications and graft and patient survival. Materials and methods Retrospective review including 291 patients who had all the information and covering a period of 10 years (2007–2017). Using a receiver operating characteristic curve, a cut-off point that would have the greatest impact on the probability of being alive at 5 years was established. In relation to this value, 2 groups were formed (low and high flow) and demographic variables, intraoperative variables, postoperative complications, and graft and patient survival were compared. Results A portal flow of 123 mL/min per100 g of liver tissue was established (area under the curve = 0.58), obtaining a low-flow (n = 129) and a high-flow group (n = 162). The 2 groups were similar in their preoperative characteristics, except for a higher proportion of preoperative ascites, a higher Model for End-Stage Liver Disease score and a lower weight of donors in the high-flow group. The arterial and portal flows were significantly higher in the high-flow group. In the postoperative period, the high-flow group presented a higher rate of ascites. The 5-year survival rate of patients was significantly higher in the high-flow group (76% vs 84%, P = .03). Conclusions Patients undergoing liver transplantation with an intraoperative portal vein flow measurement >123 mL/min per 100 g present a greater 5-year survival rate.

Many centers implement everolimus-based immunosuppression in liver transplant patients with hepatocellular carcinoma. We aimed to explore the potential impact of early initiated everolimus on tumor recurrence after liver transplantation.This study included 192 patients with hepatocellular carcinoma undergoing liver transplantation among who 64 individuals were prospectively enrolled (2012-2015) and received early initiated everolimus (ie, started between postoperative day 15 to 21), whereas the remaining 128 patients acted as historical controls without everolimus. Propensity score matching was performed to ensure comparability. Multivariate Cox regression and competing risks analysis were used to control for potential confounders.Patients with and without everolimus were comparable in terms of number of nodules (P = 0.37), total tumor diameter (P = 0.44), Milan criteria fulfillment (P = 0.56), and histological differentiation (P = 0.61), but there were increased microvascular invasion rates in the everolimus group (26.5% vs 13.3%; P = 0.026). Tumor recurrence rates were similar with and without everolimus (10.9% vs 9.9% at 36 months respectively; P = 0.18). After controlling for microvascular invasion among other potential confounders, everolimus had no significant impact on tumor recurrence, neither in the multivariate Cox regression (relative risk = 3.23; P = 0.09), nor in the competing risks analysis for tumor recurrence-death (relative risk = 1.02; P = 0.94). Patients receiving everolimus had reduced tacrolimus trough concentrations and lower serum creatinine within the first 18 months postliver transplantation.Everolimus may not be universally prescribed to prevent tumor recurrence in liver transplant patients with hepatocellular carcinoma. Future randomized trials should be focused on patients with histological features of increased tumor aggressiveness, in whom the potential benefit would be higher.

Aging is an important risk factor for patients with atrial fibrillation. The estimated prevalence of atrial fibrillation in patients aged ≥80 years is 9–10%, and is associated with a four to five fold increased risk of embolic stroke, and with an estimated increased stroke risk of 1.45-fold per decade in aging. Older age is also associated with an increased risk of major bleeding with oral anticoagulant therapy. This review will focus on the role of oral anticoagulation with new oral anticoagulants, non-vitamin K antagonist in populations with common comorbid conditions, including age, chronic kidney disease, coronary artery disease, on multiple medication, and frailty. In patients 75 years and older, randomised trials have shown new oral anticoagulants to be as effective as warfarin, or in some cases superior, with an overall better safety profile, consistently reducing rates of intracranial haemorrhages. Prior to considering oral anticoagulant therapy in an elderly frail patient, a comprehensive assessment should be performed to include the risks and benefits, stroke risk, baseline kidney function, cognitive status, mobility and fall risk, multiple medication, nutritional status assessment, and life expectancy.

This work was supported by research grants from CIBER de Epidemiologia y Salud Publica (CIBERESP), Instituto de Salud Carlos III, Junta de Andalucia, European Regional Development Fund-FEDER (PI16/01858, PI16/01812, PI20/01568 and PI-13/02406) and Generalitat Valenciana. Dr. G Cakmak is awarded a grant by The Scientific and Technological Research Council of Turkey (TUBITAK-2219). Dr. JP Arrebola is under contract within the Ramón y Cajal Program (RYC-2016-20155, Ministerio de Economia, Industria y Competitividad, Spain)., These results would not have been achieved without the selfless collaboration of the staff from Santa Ana and San Cecilio Hospitals and the participants who took part in the study., Humans are exposed to a myriad of chemical substances in both occupational and environmental settings. Persistent organic pollutants (POPs) have drawn attention for their adverse effects including cancer and endocrine disruption. Herein, the objectives were 1) to describe serum and adipose tissue retinol levels, along with serum retinol binding protein 4 (RBP4) concentrations, and 2) to assess the associations of adipose tissue POP levels with these retinoid parameters, as well as their potential interaction with the previously-observed POP-related disruption of redox microenvironment. Retinol was measured in both serum and adipose tissue along with RBP4 levels in serum samples of 236 participants of the GraMo adult cohort. Associations were explored by multivariable linear regression analyses and Weighted Quantile Sum regression. Polychlorinated biphenyls (PCBs) 180, 153 and 138 were related to decreased adipose tissue retinol levels and increased serum RBP4/retinol ratio. Dicofol concentrations > limit of detection were associated with decreased retinol levels in serum and adipose tissue. Additionally, increased adipose tissue retinol levels were linked to an attenuation in previously-reported associations of adipose tissue PCB-153 with in situ superoxide dismutase activity. Our results revealed a suggestive link between retinoids, PCBs and redox microenvironment, potentially relevant for both mechanistic and public health purposes., CIBER de Epidemiologia y Salud Publica (CIBERESP), Instituto de Salud Carlos III, Junta de Andalucia, European Commission PI16/01858 PI16/01812 PI20/01568 PI-13/02406, Generalitat Valenciana, European Commission, Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) TUBITAK-2219, Ramon y Cajal Program (Ministerio de Economia, Industria y Competitividad, Spain) RYC-2016-20155

Background: In potentially severe diseases in general and COVID-19 in particular, it is vital to early identify those patients who are going to develop complications. The last update of a recent living systematic review dedicated to predictive models in COVID-19,[1] critically appraises 145 models, 8 of them focused on prediction of severe disease and 23 on mortality. Unfortunately, in all 145 models, they found a risk of bias significant enough to finally "not recommend any for clinical use". Authors suggest concentrating on avoiding biases in sampling and prioritising the study of already identified predictive factors, rather than the identification of new ones that are often dependent on the database. Our objective is to develop a model to predict which patients with COVID-19 pneumonia are at high risk of developing severe illness or dying, using basic and validated clinical tools.Methods: prospective cohort of consecutive patients admitted in a teaching hospital during the “first wave” of the COVID-19 pandemic. Follow-up to discharge from hospital. Multiple logistic regression selecting variables according to clinical and statistical criteria. Results: 404 consecutive patients were evaluated, 392 (97%) completed follow-up. Mean age was 61 years; 59% were men. The median burden of comorbidity was 2 points in the Age-adjusted Charlson Comorbidity Index, CRB was abnormal in 18% of patients and basal oxygen saturation on admission lower than 90% in 18%. A model composed of Age-adjusted Charlson Comorbidity Index, CRB score and basal oxygen saturation can predict unfavorable evolution or death with an area under the ROC curve of 0.85 (95% CI: 0.80-0.89), and 0.90 (95% CI: 0.86 to 0.94), respectively.Conclusion: prognosis of COVID-19 pneumonia can be predicted in the out-of-hospital environment using two classic prognostic scales and a pocket pulse oximeter.

Objective To explore hypersensitivity to pain and musculoskeletal impairments in the lumbopelvic area in women with and without endometriosis. Methods This cross-sectional study included 66 women (41 women with endometriosis and 25 healthy women). Pain and related catastrophizing thoughts were assessed through a numeric rating scale, pressure pain thresholds (PPTs), the slump test, and the Pain Catastrophizing Scale. Lumbopelvic muscles were evaluated through ultrasound imaging, flexor/extensor resistance tests, and the lumbopelvic stability test. Results Women with endometriosis showed increased self-reported intensity of current pelvic pain (CuPP), reduced local PPTs (42.8–64.7% in the affected area, P-value Conclusions The presence of pain sensitization signs and lumbopelvic impairments, more pronounced in patients with stage IV endometriosis and moderate/severe CuPP, warrants the development of rehabilitation interventions targeting pain and lumbopelvic impairments in women with endometriosis.

Background Individual studies have reported widely variable rates for VTE and bleeding among hospitalized patients with coronavirus disease 2019 (COVID-19). Research Question What is the incidence of VTE and bleeding among hospitalized patients with COVID-19? Methods In this systematic review and meta-analysis, 15 standard sources and COVID-19-specific sources were searched between January 1, 2020, and July 31, 2020, with no restriction according to language. Incidence estimates were pooled by using random effects meta-analyses. Heterogeneity was evaluated by using the I2 statistic, and publication bias was assessed by using the Begg and Egger tests. Results The pooled incidence was 17.0% (95% CI, 13.4-20.9) for VTE, 12.1% (95% CI, 8.4-16.4) for DVT, 7.1% (95% CI, 5.3-9.1) for pulmonary embolism (PE), 7.8% (95% CI, 2.6-15.3) for bleeding, and 3.9% (95% CI, 1.2-7.9) for major bleeding. In subgroup meta-analyses, the incidence of VTE was higher when assessed according to screening (33.1% vs 9.8% by clinical diagnosis), among patients in the ICU (27.9% vs 7.1% in the ward), in prospective studies (25.5% vs 12.4% in retrospective studies), and with the inclusion of catheter-associated thrombosis/isolated distal DVTs and isolated subsegmental PEs. The highest pooled incidence estimate of bleeding was reported for patients receiving intermediate- or full-dose anticoagulation (21.4%) and the lowest in the only prospective study that assessed bleeding events (2.7%). Interpretation Among hospitalized patients with COVID-19, the overall estimated pooled incidence of VTE was 17.0%, with higher rates with routine screening, inclusion of distal DVT, and subsegmental PE, in critically ill patients and in prospective studies. Bleeding events were observed in 7.8% of patients and were sensitive to use of escalated doses of anticoagulants and nature of data collection. Additional studies are required to ascertain the significance of various thrombotic events and to identify strategies to improve patient outcomes. Trial Registry PROSPERO; No.: CRD42020198864; URL: https://www.crd.york.ac.uk/prospero/.

To explore work performance status in Spanish women with endometriosis and to identify those endometriosis-related symptoms that potentially contribute to the reduced work performance.Cross-sectional study.Spain.Women with endometriosis working at enrolment (n = 148).Work performance status was assessed through the Work Role Functioning Questionnaire (WRFQ). Endometriosis-related symptoms (pelvic pain, catastrophizing thoughts related to pain, chronic fatigue, sleep quality, mood status, gastrointestinal discomfort and social support) were also evaluated through validated scales. Statistical analyses were performed through multivariate linear regression analyses.Work performance status.Median WRFQ score was 72.0, with the lowest scores found in demands related to worker's needs to manage the workday from beginning to end and those dynamic and static physical loads required in the conduct of work duties. Severe pelvic pain, depressive mood and poorer sleep quality was inversely related to work performance status (p-values0.020). Finally, self-perceived social support was borderline associated with better work performance (p = 0.057). Considered together, these four psychosocial factors were responsible to explain the 37.9 % of the limitations on work performance observed in our study sample.Spanish women with endometriosis reported lower WRQF scores (predominantly in work scheduling and physical demands) in comparison with previous studies on Spanish healthy adults. Psychosocial factors, including pelvic pain, sleep quality and depressive mood are related with work performance status. Thus, the effectiveness of physical and psychological rehabilitation programs in work productivity in women with endometriosis should be evaluated in the close future.

This study investigated the effect of a 3-week power-oriented resistance training program performed at moderate altitude on leg power output variables in a countermovement jump, a related judo technique (ippon-seoi-nage) and the relationship between them. Twenty-four elite male judokas were randomly assigned to a hypobaric hypoxia or normoxia group. Mechanical outputs from an incremental loaded countermovement jump test and the kinematic variables transferred to a dummy during an ippon-seoi-nage test (time to execution and movement accelerations) were assessed before, after, 1 and 2 weeks after training. Results indicated an increase in explosive leg capacity both at moderate altitude (2320 m.a.s.l.) and sea level. The hypoxia group showed additional benefits when compared to normoxia group for peak velocities with different percentages of the body weight, maximal theoretical velocity and jump height after the training period, and these additional benefits in jump height were maintained 2 weeks after training. The hypoxia group achieved a higher peak performance in peak velocity and jump height than normoxia group (peak velocity: 8.8 vs. 5.6%, jump height: 8.2 vs. 1.4%, respectively) and was achieved earlier in hypoxia (after training) than in normoxia (1 week after training). However, there was a detrimental effect for the hypoxia group on the times of execution and acceleration of the ippon-seoi-nage compared to the normoxia group. These results suggest that altitude training may induce faster and greater improvements in explosive leg extension capacity. Specific technique-oriented training should be included at altitude to prevent technique impairment., Spanish Ministry of Economy, Industry and Competitiveness DEP2015-64350-P BES-2016-078035

The performance of validated bleeding risk scores in patients with venous thromboembolism (VTE) could be different depending on the time after index event or the site of bleeding. In this study we compared the "classic" Registro Informatizado de Enfermedad TromboEmbólica (RIETE) score and the more recently developed VTE-BLEED score for the prediction of major bleeding in patients under anticoagulant therapy in different time intervals after VTE diagnosis. Out of 82,239 patients with acute VTE, the proportion of high-risk patients according to the RIETE and VTE-BLEED scores was 7.1 and 62.3%, respectively. The performance of both scores across the different study periods (first 30 days after VTE diagnosis, days 31-90, days 91-180, and days 181-360) was similar, with areas under the receiving operating characteristics (ROC) curve (AUC) ranging between 0.69 and 0.72. However, the positive predictive values were low, ranging between 0.6 and 3.9 (better for early major bleeding than for later periods). A sensitivity analysis limited to patients with unprovoked VTE showed comparable results. Both scores showed a trend toward a better prediction of extracranial than intracranial major bleeding, the RIETE score resulting more useful for early extracranial bleeding and the VTE-BLEED for late intracranial hemorrhages. Our study reveals that the usefulness of available bleeding scores may vary depending on the characteristics of the patient population and the time frame evaluated. Dynamic scores could be more useful for this purpose. ispartof: TH Open vol:5 issue:3 pages:e319-e328 ispartof: location:Germany status: Published online

International audience; Objective: To analyse the rates of lower limb muscle injuries in athletics disciplines requiring different running velocities during international athletics championships.Design: Prospective total population study.Methods: During 13 international athletics championships (2009–2019) national medical teams and local organizing committee physicians daily reported all newly incurred injuries using the same study design, injury definition and data collection procedures. In-competition lower limb muscle injuries of athletes participating in disciplines involving running (i.e. sprints, hurdles, jumps, combined events, middle distances, long distances, and marathon) were analysed.Results: Among the 12,233 registered athletes, 344 in-competition lower limb muscle injuries were reported (36% of all in-competition injuries). The proportion, incidence rates and injury burden of lower limb muscles injuries differed between disciplines for female and male athletes. The most frequently injured muscle group was hamstring in sprints, hurdles, jumps, combined events and male middle distances runners (43–75%), and posterior lower leg in female middle distances, male long distances, and female marathon runners (44–60%). Hamstring muscles injuries led to the highest burden in all disciplines, except for female middle distance and marathon and male long distance runners. Hamstring muscles injury burden was generally higher in disciplines requiring higher running velocities, and posterior lower leg muscle injuries higher in disciplines requiring lower running velocities.Conclusions: The present study shows discipline-specific injury location in competition context. Our findings suggest that the running velocity could be one of the factors that play a role in the occurrence/location of muscle injuries.

We aimed to assess the relationships among the adipose tissue’s (AT) oxidative microenvironment, in situ accumulated persistent organic pollutant (POP) concentrations, and cancer development. POP and oxidative stress levels were quantified in AT samples from 382 adults recruited within the GraMo cohort (2003−2004) in Granada (Spain). The 16-year cancer incidence was ascertained by reviewing health/administrative databases. Cox-regression models and mediation analyses were performed. The enzymes superoxide dismutase (SOD) and glutathione reductase (GRd) were positively associated with the risk of non-hormone-dependent (NHD) cancer [adjusted hazard ratio (HR) 1.76; 95% confidence interval (CI): 1.17, 2.64 and HR 2.35; 95% CI: 1.41, 3.94, respectively]. After adjustment for covariates, polychlorinated biphenyl-138 (PCB-138) (HR 1.78; 95% CI: 1.03, 3.09), β-hexachlorocyclohexane (β-HCH) (HR 1.70; 95% CI: 1.09, 2.64), and hexachlorobenzene (HR 1.54; 95% CI: 1.02, 2.33) were also positively associated with the risk of NHD cancer. Although confidence intervals included the null value, probably because of the modest number of cancer cases, we observed a potential mediation effect of SOD and GRd on the associations between β-HCH and the risk of NHD tumors (percent mediated = 33 and 47%, respectively). Our results highlight the relevance of human AT’s oxidative microenvironment as a predictor of future cancer risk as well as its potential mediating role on POP-related carcinogenesis. Given their novelty, these findings should be interpreted with caution and confirmed in future studies., Ramon y Cajal Program (Ministerio de Economia, Industria y Competitividad, Spain) RYC-2016-20155, Instituto de Salud Carlos III FI17/00310, Junta de Andalucia, European Commission PI16/01858 BA15/00093 EF-0428-2016 PI20/01568 Human Biomonitoring for Europe Project (European Union Commission H2020-EJP-HBM4EU

The authors thank the Asociación Española Contra el Cáncer (IDEAS19055CANT), the Spanish Ministry of Education Culture and Sport (MECD) (FPU17/00939, FPU18/03575), the Carlos III Health Institute (FI19/00230), and Carlos III Health Insitute and the European Regional Development Fund (FEDER) (PI18/01840), for funding this study and all participants of the study. IEC is supported by the Spanish Ministry of Economy and Competitiveness. This study was part of a Ph.D thesis conducted in the Clinical Medicine and Public Health Doctoral Studies of the University of Granada, Spain. Trial registration: ClinicalTrials. Gov identifier: NCT04583124., A current challenge in breast cancer (BC) patients is how to reduce the side effects of cancer and cancer treatments and prevent a decrease in quality of life (QoL). Neurotoxic side effects, especially from chemotherapy, are present in up to 75% of women with BC, which implies a large impact on QoL. There is a special interest in the preventive possibilities of therapeutic exercise (TE) for these neurological sequelae, and the benefits of TE could be improved when it is combined with vagal activation techniques (VATs). This superiority randomized controlled trial aims to examine the feasibility and efficacy of an 8-week multimodal intervention (ATENTO) based on moderate-vigorous intensity and individualized TE (aerobic and strength exercises) and VAT (myofascial and breathing exercises), on neurotoxicity prevention in women with BC before starting adjuvant chemotherapy (ATENTO-B) versus throughout adjuvant chemotherapy (ATENTO-T). A sample of 56 women newly diagnosed with BC, as calculated with a power of 85%, will be randomly allocated into these two groups. This study could provide an impetus for the introduction of early multimodal intervention methods to prevent neurotoxicity and consequently avoid the QoL deterioration that BC patients presently suffer throughout their treatments., Fundacion Cientifica Asociacion Espanola Contra el Cancer IDEAS19055CANT, Spanish Ministry of Education Culture and Sport FPU17/00939 FPU18/03575, Instituto de Salud Carlos III FI19/00230 PI18/01840, Fondos Estructurales de la Union Europea (FEDER) PI18/01840, Spanish Ministry of Economy and Competitiveness

Neurofibrillary tangle (NFT) pathology in the medial temporal lobe (MTL) is closely linked to neurodegeneration, and is the early pathological change associated with Alzheimer’s Disease (AD). In this work, we investigate the relationship between MTL morphometry features derived from high-resolution ex vivo imaging and histology-based measures of NFT pathology using a topological unfolding framework applied to a dataset of 18 human postmortem MTL specimens. The MTL has a complex 3D topography and exhibits a high degree of inter-subject variability in cortical folding patterns which poses a significant challenge for volumetric registration methods typically used during MRI template construction. By unfolding the MTL cortex, the proposed framework explicitly accounts for the sheet-like geometry of the MTL cortex and provides a two-dimensional reference coordinate space which can be used to implicitly register cortical folding patterns across specimens based on distance along the cortex despite large anatomical variability. Leveraging this framework in a subset of 15 specimens, we characterize the associations between NFTs and morphological features such as cortical thickness and surface curvature and identify regions in the MTL where patterns of atrophy are strongly correlated with NFT pathology.

Background Venous thromboembolism (VTE) is a major cause of morbidity and mortality postoperatively. The use of pharmacologic prophylaxis is effective in reducing the incidence of VTE. However, the prophylaxis is often discontinued at hospital discharge, especially for those with benign disease. The implications of this practice are not known. We assessed the data from a large, ongoing registry regarding the time course of VTE and outcomes after noncancer surgery. Methods We analyzed the RIETE (Computerized Registry on Venous Thromboembolism) registry, which includes data from consecutive patients with symptomatic confirmed VTE. In the present study, we focused on general surgical patients who had developed symptomatic postoperative VTE in the first 8 weeks after noncancer surgery. The main objective was to assess the interval between surgery and the occurrence of VTE. Additional variables included the clinical presentation associated with the event, the use of thrombosis prophylaxis, and unfavorable outcomes. Results The data from 3296 patients were analyzed. The median time from surgery to the detection of VTE was 16 days (interquartile range, 8-30 days). Of the VTE events, 77% were detected after the first postoperative week and 27% after 4 weeks. Overall, 43.9% of the patients with VTE had received pharmacologic prophylaxis after surgery for a median of 8 days (interquartile range, 5-14 days), and three quarters of the VTE events were detected after pharmacologic prophylaxis had been discontinued. Overall, 54% of the patients with VTE had presented with pulmonary embolism. For 15% of the patients, the clinical outcome was unfavorable, including 4% who had died within 90 days. Conclusions The risk of VTE after noncancer general surgery remains high for ≤2 months. More than one half of the patients had presented with symptomatic PE as the VTE event, and 15% had had unfavorable outcomes. Only 44% of these patients had received pharmacologic prophylaxis for around 1 week.