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Background : Sarcopenia is defined as a loss of muscle mass, strength, and physical function associated with aging. It is due to a combination of genetic, environmental, and physiological factors. It is also associated with an increased risk of health problems. Since there are many different researchers in the field, with their own algorithms and cut-off points, there is no single criterion for diagnosis. This review aims to compare the prevalence of sarcopenia according to these different diagnostic criteria in older adult populations by age group and sex. Methods : Different databases were searched: Web of Science, Pubmed, Dialnet, Scopus, and Cochrane. The keywords used were "sarcopenia", "diagnosis", "prevalence", "assessment", "aged", "aging" and "older". Studies conducted in a population aged ≥65 assessing the prevalence of sarcopenia were selected. Results : Nineteen articles met the inclusion criteria, with a total of 33,515 subjects, 38.08% female and 61.42% male, at a mean age of 74.52. The diagnostic algorithms used were 52.63% AWGS2, 21.05% EWGSOP2, 10.53% AWGS1 and EWGS1, and 5.26% FNIH. Prevalence ranged from 1.7% to 37.47%, but was higher in males and increased with age. Conclusions : The prevalence of sarcopenia varies depending on the diagnostic algorithm used, but it increases with age and is higher in men. The EWGSOP2 and AWGS2 are the most used diagnostic criteria and measure the same variables but have different cut-off points. Of these two diagnostic algorithms, the one with the highest prevalence of sarcopenia and severe sarcopenia is the AWGS2. These differences may be due to the use of different tools and cut-off points. Therefore, a universal diagnostic criterion should be developed to allow early diagnosis of sarcopenia.

Introduction: Previous studies have reported a correlation between a high-grade CMV-infection and an unfavorable prognosis in glioblastoma (GB). Coversely, epilepsy has been associated with a more favorable outcome in GB patients. Despites epilepsy and CMV share similar molecular mechanisms in GB tumoral microenvironment, the correlation between Tumor-Related-Epilepsy (TRE) and CMVinfection remains unexplored. The aim of our study is to examine the correlation between the dregree of CMV infection and seizure types on the survival of TRE Adult-type-diffuse-glioma. To achieve this objective, we conducted a comprehensive literature review to assess our results regarding previous publications., Methods: We conducted a retrospective-observational study on TRE Adult-type-diffuse-gliomas treated at a single center in Mexico from 2010 to 2018. Tumor tissue and cDNA were analyzed by immunochemistry (IHC) for CMV (IE and LA antigens) at the Karolinska Institute in Sweden, and RT-PCR for CMV-gB in Torreon Mexico, respectively. Bivariate analysis ( X 2- test ) was performed to evaluate the association between subtypes of Adult-type-diffuse-glioma (IDH-mut grade 4 astrocytoma vs. IDH-wt glioblastoma) and the following variables: type of hemispheric involvement (mesial vs. neocortical involvement), degree of CMV infection (<25%vs. >25% infected-tumoral cells) and seizure types [Focal awareness, focal impaired awareness, and FBTCS]. Kaplan Meier and Cox analyses were performed to determine the risk, p < 0.05 was considered statistically significant., Results: Sixty patients with TRE Adult type diffuse gliomas were included (80% IDH-wt glioblastoma and 20% IDH-mut grade 4astrocytomas). The mean age was 61.5 SD ± 18.4, and 57% were male. Fifty percent of the patients presented with mesial involvement of the hemysphere. Seizure types included focal awareness (15%), focal impaired awareness (43.3%), and FBTCS (41.7%). Ninety percent of cases were treated with Levetiracetam and 33.3% presented Engel-IA postoperative seizure control. More than 90% of samples were positive for CMV-immunohistochemistry (IHC). However, all cDNA analyzed by RT-PCR return negative results. The median of overall survival (OS) was 15 months. High-grade CMV-IE infection (14 vs. 25 months, p<0.001), mesial involvement (12 vs. 18 months, p<0.001), and FBTCS were associated with worse OS (9 vs.18 months for non-FBTCS). Multivariate analysis demonstrated that high-grade CMV infection (HR = 3.689, p=0.002) and FBTCS (HR=7.007, p<0.001) were independent unfavorable survival factors., Conclusions: CMV induces a proinflammatory tumoral microenvironment that contributes to the developmet of epilepsy. Tumor progression could be associated not only with a higher degree of CMV infection but also to epileptogenesis, resulting in a seizure phenotype chracterized by FBTCS and poor survival outcomes. This study represents the first survival analysis in Latin America to include a representative sample of TRE Adult-type diffuse gliomas considering CMV-infection-degree and distinguishing features (such as FBTCS) that might have potential clinical relevance in this group of patients. Further prospective studies are required to validate these results., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Introduction: The impact of Medicaid expansion (ME) on the treatment of patients with cancer remains controversial, especially individuals requiring complex multidisciplinary care. We sought to evaluate the impact of Medicaid expansion (ME) on receipt of multimodal care, including surgical resection, for Stage I-III biliary tract cancer (BTC)., Methods: Patients diagnosed with BTC between 40 and 65 years of age were identified from the National Cancer Database and divided into pre- (2008-2012) and post- (2015-2018) ME cohorts. Difference-in-difference (DID) analysis was used to determine the impact of ME on the utilization of surgery and multimodal chemotherapy and/or radiotherapy treatment for BTC., Results: Among 12,415 patients with BTC (extrahepatic, n = 5622, 45.3%; intrahepatic, n = 4352, 35.1%; gallbladder, n = 1944, 15.7%; overlapping, n = 497, 4.0%), 5835 (47.0%) and 6580 (53.0%) patients were diagnosed before versus after ME, respectively. Overall utilization of surgery (OR 1.13, 95% CI 1.02-1.26) and multimodality therapy (OR 1.13, 95% CI 1.01-1.27) increased in states that adopted ME. Utilization of surgery among uninsured/Medicaid patients in ME states increased relative to patients living in non-ME states (∆+10.1%, p = 0.01). Similarly, the use of multimodal treatment increased among uninsured/Medicaid patients living in ME versus non-ME states (∆+6.4%, p = 0.04); in contrast, there were no difference among patients with other insurance statuses (overall: ∆+1.5%, private: ∆-2.0%, other: ∆+3.9%, all p > 0.5). Uninsured/Medicaid patients with BTC who lived in a ME state had a lower risk of long-term death in the post-ME era (HR 0.81, 95% CI 0.67-0.98; p = 0.03)., Conclusions: Implementation of ME positively impacted survival among patients who underwent surgical and multimodal treatment for Stage I-III BTC., (© 2023 Wiley Periodicals LLC.)

Treatment options for patients with secondary acute myeloid leukemia (sAML) and AML with myeloid-related changes (AMLMRC) aged 60 to 75 years are scarce and unsuitable. A pivotal trial showed that CPX-351 improved complete remission with/without incomplete recovery (CR/CRi) and overall survival (OS) as compared with standard "3+7" regimens. We retrospectively analyze outcomes of 765 patients with sAML and AML-MRC aged 60 to 75 years treated with intensive chemotherapy, reported to the PETHEMA registry before CPX-351 became available. The CR/CRi rate was 48%, median OS was 7.6 months (95% confidence interval [CI]: 6.7-8.5) and event-free survival (EFS) 2.7 months (95% CI: 2-3.3), without differences between intensive chemotherapy regimens and AML type. Multivariate analyses identified age ≥70 years, Eastern Cooperative Oncology Group performance status ≥1 as independent adverse prognostic factors for CR/CRi and OS, while favorable/intermediate cytogenetic risk and NPM1 were favorable prognostic factors. Patients receiving allogeneic stem cell transplant (HSCT), autologous HSCT, and those who completed more consolidation cycles showed improved OS. This large study suggests that classical intensive chemotherapy could lead to similar CR/CRi rates with slightly shorter median OS than CPX-351.

Introduction: In recent years, the vegetarian diet has increased in popularity among athletes. The aim of this review is to ascertain the differences in variables related to performance, nutritional intake, and health in athletes according to whether they are omnivores or vegetarians., Methodology: A literature search was carried out in different databases: PubMed, Web of Science, Dialnet, and Cochrane. The keywords used were "vegetarian diet", "vegan diet", "exercise", "sport", and "performance". After applying different inclusion criteria, six studies were included in the review., Results: No significant differences were obtained in variables related to physical performance (adherence exercise, Vo2Máx, muscle power, and sprint test) or health (body composition, psychological well-being, and social relationships), but dietary intake was significantly higher in carbohydrates and lower in proteins in vegetarian athletes ( p < 0.05)., Conclusions: It cannot be affirmed that vegetarian subjects have a higher sports performance, for which more research should be carried out.

Background: The aims of this study were to analyse the effect of creatine supplementation on the performance improvement in a bench pressing (BP) strength test of muscle failure and to evaluate muscle fatigue and metabolic stress 20 min after the exercise., Methods: Fifty young and healthy individuals were randomly assigned to a creatine group ( n = 25) or a placebo group ( n = 25). Three exercise sessions were carried out, with one week of rest between them. In the first week, a progressive load BP test was performed until the individuals reached the one repetition maximum (1RM) in order to for us obtain the load-to-velocity ratio of each participant. In the second week, the participants conducted a three-set BP exercise protocol against 70% 1RM, where they performed the maximum number of repetitions (MNR) until muscle failure occurred, with two minutes of rest between the sets. After one week, and following a supplementation period of 7 days, where half of the participants consumed 0.3 g·kg -1 ·day -1 of creatine monohydrate (CR) and the other half consumed 0.3 g·kg -1 ·day -1 of placebo (PLA, maltodextrin), the protocol from the second week was repeated. After each set, and up to 20 min after finishing the exercise, the blood lactate concentrations and mean propulsive velocity (MPV) at 1 m·s -1 were measured., Results: The CR group performed a significantly higher number of repetitions in Set 1 (CR = 14.8 repetitions, PLA = 13.6 repetitions, p = 0.006) and Set 2 (CR = 8 repetitions, PLA = 6.7 repetitions, p = 0.006) after supplementation, whereas no significant differences were seen in Set 3 (CR = 5.3 repetitions, PLA = 4.7 repetitions, p = 0.176). However, there was a significant increase in blood lactate at minute 10 ( p = 0.003), minute 15 ( p = 0.020), and minute 20 ( p = 0.015) after the exercise in the post-supplementation period. Similarly, a significant increase was observed in the MPV at 1 m·s -1 in the CR group with respect to the PLA group at 10, 15, and 20 min after the exercise., Conclusions: Although the creatine supplementation improved the performance in the strength test of muscle failure, the metabolic stress and muscle fatigue values were greater during the 20 min of recovery.

Objective: The importance of extent of resection (EOR) in glioblastoma (GBM) has been thoroughly demonstrated. However, few studies have explored the practices and benefits of early repeat resection (ERR) when residual tumor deemed resectable is unintentionally left after an initial resection, and the survival benefit of ERR is still unknown. Herein, the authors aimed to internationally survey current practices regarding ERR and to analyze differences based on geographic location and practice setting., Methods: The authors distributed a survey to the American Association of Neurological Surgeons and Congress of Neurological Surgeons Tumor Section, Society of British Neurological Surgeons, European Association of Neurosurgical Society, and Latin American Federation of Neurosurgical Societies. Neurosurgeons responded to questions about their training, practice setting, and current ERR practices. They also reported the EOR threshold below which they would pursue ERR and their likelihood of performing ERR using a Likert scale of 1-5 (5 being the most likely) in two sets of 5 cases, the first set for a patient's initial hospitalization and the second for a referred patient who had undergone resection elsewhere. The resection likelihood index for each respondent was calculated as the mean Likert score across all cases., Results: Overall, 180 neurosurgeons from 25 countries responded to the survey. Neurosurgeons performed ERRs very rarely in their practices (< 1% of all GBM cases), with an EOR threshold of 80.2% (75%-95%). When presented with 10 cases, the case context (initial hospitalization vs referred patient) did not significantly change the surgeon ERR likelihood, although ERR likelihood did vary significantly on the basis of tumor location (p < 0.0001). Latin American neurosurgeons were more likely to pursue ERR in the provided cases. Neurosurgeons were more likely to pursue ERR when the tumor was MGMT methylated versus unmethylated, with a resection likelihood index of 3.78 and 3.21, respectively (p = 0.004); however, there was no significant difference between IDH mutant and IDH wild-type tumors., Conclusions: Results of this survey reveal current practices regarding ERR, but they also demonstrate the variability in how neurosurgeons approach ERR. Standardized guidelines based on future studies incorporating tumor molecular characteristics are needed to guide neurosurgeons in their decision-making on this complicated issue.

Structural health monitoring (SHM) in an electric arc furnace is performed in several ways. It depends on the kind of element or variable to monitor. For instance, the lining of these furnaces is made of refractory materials that can be worn out over time. Therefore, monitoring the temperatures on the walls and the cooling elements of the furnace is essential for correct structural monitoring. In this work, a multivariate time series temperature prediction was performed through a deep learning approach. To take advantage of data from the last 5 years while not neglecting the initial parts of the sequence in the oldest years, an attention mechanism was used to model time series forecasting using deep learning. The attention mechanism was built on the foundation of the encoder-decoder approach in neural networks. Thus, with the use of an attention mechanism, the long-term dependency of the temperature predictions in a furnace was improved. A warm-up period in the training process of the neural network was implemented. The results of the attention-based mechanism were compared with the use of recurrent neural network architectures to deal with time series data, such as Long Short-Term Memory (LSTM) and Gated Recurrent Unit (GRU). The results of the Average Root Mean Square Error (ARMSE) obtained with the attention-based mechanism were the lowest. Finally, a variable importance study was performed to identify the best variables to train the model.

Background: Discrimination, abuse, and mistreatment are prevailing problems reported in neurosurgical training programs globally. Moreover, the current coronavirus disease 2019 (COVID-19) pandemic may also show a negative impact on burnout levels in neurosurgery residents. This study aims to evaluate burnout, discrimination, and mistreatment in neurosurgical residents training in Latin America during the severe acute respiratory syndrome coronavirus 2 era., Methods: A 33-item electronic survey was sent to neurosurgery residents from Latin America from May 10 to 25, 2021. Statistical analysis was performed using SPSS version 25., Results: A total of 111 neurosurgery residents responded to the survey. Mean age was 29.39 ± 2.37 years; 22.5% were female and 36% were training in Mexico. Residents who reported experiencing discrimination for testing positive to COVID-19 had the highest levels of depersonalization (66.7%; P = 0.043) and emotional exhaustion (75%; P = 0.023). Female respondents reported higher rates of gender discrimination (80% vs. 1.2%; P = 0.001), abuse (84% vs. 58.1%; P < 0.005), and sexual harassment (24% vs. 0%; P < 0.001) than did male respondents. Residents training in Mexico reported lower rates of emotional or verbal abuse (59.2% vs. 32.5%; P = 0.007) and bullying (P < 0.005) than did those in other countries in Latin America. Older age was a protective factor for high depersonalization scores (odds ratio [OR], 0.133; 95% confidence interval [CI], 0.035-0.500). Experiencing discrimination represented a risk factor for presenting high emotional exhaustion scores (OR, 3.019; 95% CI, 1.057-8.629). High levels of depersonalization were associated with a 7-fold increased risk of suicidal ideation (OR, 7.869; 95% CI, 1.266-48.88)., Conclusions: The COVID-19 pandemic has been a significant burden on several aspects of health care workers' lives. Our results provide a broad overview of its impact on burnout, discrimination, and mistreatment as experienced by neurosurgery residents training in Latin America, laying the groundwork for future studies and potential interventions., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The focused attention training has been used in pre surgery patients because of the benefits of its use decrease of psychological symptoms like anxiety, eases the post operatory period and recovery. Also, there are favorable changes in a psychological level as well as pain healing., Objective: Show that the focused attention training is effective in patients who are candidates to a craniotomy., Method: The study includes 11 participants in an age of 29 to 60 age from the Hospital de Especialidades del Centro Médico Nacional Siglo XXI, from May to September 2021. The Hospital Anxiety and Depression Scale (HADS) was applied pre, post and follow-up, to search anxiety symptoms and the focused attention training was used in the 11 patients., Results: The data was analyzed and checked with the Friedman test, for not parametric data and to identify differences in anxiety levels. It was observed that there are differences (p < 0.05) in both anxiety and depression., Conclusions: Anxiety decreased significantly before and after the focused attention training, the follow-up was kept the same way for 40 days; which means the training helped the patient to decrease anxiety., (Copyright: © 2022 Permanyer.)

Background: Recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic represents an important negative impact on global training of neurosurgery residents. Even before the pandemic, discrimination is a challenge that neurosurgical residents have consistently faced. In the present study, we evaluated discriminatory conditions experienced by residents during their neurosurgical training in Mexico before the SARS-CoV-2 pandemic., Methods: An electronic survey of 18 questions was sent among residents registered in the Mexican Society of Neurological Surgery (MSNS), between October 2019 and July 2020. Statistical analysis was made in IBM SPSS Statistics 25. The survey focused on demographic characteristics, discrimination, personal satisfaction, and expectations of residents., Results: A response rate of 50% (132 of 264 residents' members of MSNS) was obtained and considered for analysis. Median age was 30.06 ± 2.48 years, 5.3% ( n = 7) were female and 16.7% ( n = 22) were foreigners undergoing neurosurgical training in Mexico. Approximately 27% of respondents suffered any form of discrimination, mainly by place of origin (9.1%), by gender (8.3%) or by physical appearance (6.1%). About 42.9% ( n = 3) of female residents were discriminated by gender versus 6.4% ( n = 8) of male residents ( P = 0.001); while foreign residents mentioned having suffered 10 times more an event of discrimination by place of origin compared to native Mexican residents (36.4% vs. 3.6%, P < 0.001)., Conclusion: This manuscript represents the first approximation to determine the impact of discrimination suffered by residents undergoing neurosurgical training in Mexico before the SARS-CoV-2 pandemic., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Surgical Neurology International.)

The analysis of data from sensors in structures subjected to extreme conditions such as the ones used in smelting processes is a great decision tool that allows knowing the behavior of the structure under different operational conditions. In this industry, the furnaces and the different elements are fully instrumented, including sensors to measure variables such as temperature, pressure, level, flow, power, electrode positions, among others. From the point of view of engineering and data analytics, this quantity of data presents an opportunity to understand the operation of the system under normal conditions or to explore new ways of operation by using information from models provided by using deep learning approaches. Although some approaches have been developed with application to this industry, it is still an open research area. As a contribution, this paper presents an applied deep learning temperature prediction model for a 75 MW electric arc furnace, which is used for ferronickel production. In general, the methodology proposed considers two steps: first, a data cleaning process to increase the quality of the data, eliminating both redundant information as well as atypical and unusual data, and second, a multivariate time series deep learning model to predict the temperatures in the furnace lining. The developed deep learning model is a sequential one based on GRU (gated recurrent unit) layer plus a dense layer. The GRU + Dense model achieved an average root mean square error (RMSE) of 1.19 °C in the test set of 16 different thermocouples radially distributed on the furnace.

Background: History has taught us that Mexican culture has been largely supported by women, despite gender prejudice from the society. Neurosurgery has not been the exception. Therefore, we investigated the challenges and influence of female neurosurgeons in Mexico., Methods: We conducted a review of the literature and an analysis of the internal database of the Mexican Society of Neurological Surgery focusing on 3 topics: 1) the historical presence of women and gender inequality in Mexico; 2) the life and legacy of the woman who became the first neurosurgeon in Mexico and in Latin America; and 3) the participation of women in neurosurgery in the past 3 decades., Results: In Latin America, the first woman in neurosurgery was María Cristina García-Sancho, who completed her neurosurgical training in 1951. Currently, women represent 6.2% of the total members of the Mexican Society of Neurological Surgery (MSNS). This percentage is still low, although data collected in this study suggest that it might increase in the next few years because 16.7% of Board Directors of the MSNS are women, the next elected president is a female neurosurgeon, and 14.5% of neurosurgery residents are women., Conclusions: Although a steady increase has occurred of women in neurosurgery in Mexico, there is still work to do, especially to overcome the barriers related to the old assumptions of the cultural and social roles of women., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has exerted a significant impact on health care workers. Recent studies have reported the detrimental effects of the pandemic on neurosurgery residents in North America, Asia, and Italy. However, the impact of the pandemic on neurosurgical training in Latin America and Spain has not yet been reported. In the present report, we describe effects of COVID-19 on training and working conditions of neurosurgery residents in these countries., Methods: An electronic survey with 33 questions was sent to neurosurgery residents between September 7, 2020 and October 7, 2020. Statistical analysis was made in SPSS version 25., Results: A total of 293 neurosurgery residents responded. The median age was 29.47 ± 2.6 years, and 79% (n = 231) were male. Of respondents, 36.5% (n = 107) were residents training from Mexico; 42% surveyed reported COVID symptoms and 2 (0.7%) received intensive care unit care; 61.4% of residents had been tested for COVID and 21.5% had a positive result; 84% of the respondents mentioned persisted with the same workload (≥70 hours per week) during the pandemic. Most residents from Mexico were assigned to management of patients with COVID compared with the rest of the countries (88% vs. 68.3%; P < 0.001), mainly in medical care (65.4% vs. 40.9%; P < 0.001), mechanical ventilators (16.8% vs. 5.9%; P = 0.003), and neurologic surgeries (94% vs. 83%; P = 0.006)., Conclusions: Our results offer a first glimpse of the changes imposed by the COVID-19 pandemic on neurosurgical work and training in Latin America and Spain, where health systems rely strongly on a resident workforce., (Copyright © 2021. Published by Elsevier Inc.)

Background: PSMA (prostate-specific membrane antigen) protein is heavily expressed in the proliferating microvasculature of high-grade gliomas (HGG) and brain metastases (BM). This research aimed to assess [ 99m Tc]Tc-iPSMA SPECT brain imaging as a potential specific diagnosis of HGG and BM by PSMA-targeting in their proliferating vasculature., Methods: Forty-one patients, with suspected brain tumors, as detected by enhanced MRI scanning, were enrolled to undergo preoperative [ 99m Tc]Tc-iPSMA SPECT brain imaging. Semiquantitative image analyses, to evaluate the maximum target-to-background ratio (TBRmax), were performed. All diagnoses were histopathologically confirmed. PSMA expression was evaluated by immunohistochemistry (IHC) in 11 brain tumor tissues. TBRmax values were correlated with IHC results and tumor WHO grade (HGG vs LGG)., Results: [ 99m Tc]Tc-iPSMA images showed increased uptake in BM, HGG, and recurrent gliomas (TBRmax of 25.1 ± 7.1, 18.5 ± 9.0, 15.0 ± 9.9, respectively), and was negative in treatment-naive patients with LGG and reactive gliosis. PSMA was highly expressed in the vascular endothelium of grade IV gliomas and BM, while its expression was extremely low in LGG and completely absent in gliosis. By using 2.8 as a threshold value for TBRmax, the specificity, sensitivity, PPV, NPV and accuracy were 100%, 94%, 100%, 77% and 95%, respectively., Conclusions: The results of this pilot study show that [ 99m Tc]Tc-iPSMA SPECT brain imaging is a specific and potentially useful neuroimaging tool for assessing tumoral neovasculature formation in gliomas and brain metastases., Competing Interests: Declaration of competing interest P. Vallejo-Armenta (P.V.A.), J. Soto-Andonaegui (J.S.A.), R.M. Villanueva-Pérez (R.M.V.P), J.I. González-Díaz (J.I.G.D.), K. Contreras-Contreras (K.C.C.), C.G. Bautista-Wong (C.G.B·W.), B. Sandoval-Bonilla (B.S.B.), B. Nettel-Rueda (B.N.R.), C. Santos-Cuevas (C.S.C.), and G. Ferro-Flores (G.F.F.) declare that they have no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) with high-risk (HR) features and adequate measurable residual disease (MRD) clearance remains unclear. The aim of the ALL-HR-11 trial was to evaluate the outcomes of HR Ph- adult ALL patients following chemotherapy or allo-HSCT administered based on end-induction and consolidation MRD levels. Patients aged 15 to 60 years with HR-ALL in complete response (CR) and MRD levels (centrally assessed by 8-color flow cytometry) <0.1% after induction and <0.01% after early consolidation were assigned to receive delayed consolidation and maintenance therapy up to 2 years in CR. The remaining patients were allocated to allo-HSCT. CR was attained in 315/348 patients (91%), with MRD <0.1% after induction in 220/289 patients (76%). By intention-to-treat, 218 patients were assigned to chemotherapy and 106 to allo-HSCT. The 5-year (±95% confidence interval) cumulative incidence of relapse (CIR), overall survival (OS), and event-free survival probabilities for the whole series were 43% ± 7%, 49% ± 7%, and 40% ± 6%, respectively, with CIR and OS rates of 45% ± 8% and 59% ± 9% for patients assigned to chemotherapy and of 40% ± 12% and 38% ± 11% for those assigned to allo-HSCT, respectively. Our results show that avoiding allo-HSCT does not hamper the outcomes of HR Ph- adult ALL patients up to 60 years with adequate MRD response after induction and consolidation. Better postremission alternative therapies are especially needed for patients with poor MRD clearance. This trial was registered at www.clinicaltrials.gov as # NCT01540812., (© 2021 by The American Society of Hematology.)

The lectin, galectin-3 (Gal3), has been implicated in a variety of inflammatory and oncogenic processes, including tumor growth, invasion, and metastasis. The interactions of Gal3 and MUC16 represent a potential targetable pathway for the treatment of MUC16-expressing malignancies. We found that the silencing of Gal3 in MUC16-expressing breast and ovarian cancer cells in vitro inhibited tumor cell invasion and led to attenuated tumor growth in murine models. We therefore developed an inhibitory murine monoclonal anti-Gal3 carbohydrate-binding domain antibody, 14D11, which bound human and mouse Gal3 but did not bind human Galectins-1, -7, -8 or -9. Competition studies and a docking model suggest that the 14D11 antibody competes with lactose for the carbohydrate binding pocket of Gal3. In MUC16-expressing cancer cells, 14D11 treatment blocked AKT and ERK1/2 phosphorylation, and led to inhibition of cancer cell Matrigel invasion. Finally, in experimental animal tumor models, 14D11 treatment led to prolongation of overall survival in animals bearing flank tumors, and retarded lung specific metastatic growth by MUC16 expressing breast cancer cells. Our results provide evidence that antibody based Gal3 blockade may be a viable therapeutic strategy in patients with MUC16-expressing tumors, supporting further development of human blocking antibodies against Gal3 as potential cancer therapeutics.

High-grade serous ovarian cancer (HGSOC) remains the most lethal gynecologic cancer in the United States. Genomic analysis revealed roughly half of HGSOC display homologous repair deficiencies. An improved understanding of the genomic and somatic mutations that influence DNA repair led to the development of poly(ADP-ribose) polymerase inhibitors for the treatment of ovarian cancer. In this review, we explore the preclinical and clinical studies that led to the development of FDA approved drugs that take advantage of the synthetic lethality concept, the implementation of the early phase trials, the development of companion diagnostics and proposed mechanisms of resistance., Competing Interests: The authors declare no conflict of interest.

Colorectal cancer treatment has advanced over the past decade. The drug 5-fluorouracil is still used with a wide percentage of patients who do not respond. Therefore, a challenge is the identification of predictive biomarkers. The protein kinase R (PKR also called EIF2AK2) and its regulator, the non-coding pre-mir-nc886, have multiple effects on cells in response to numerous types of stress, including chemotherapy. In this work, we performed an ambispective study with 197 metastatic colon cancer patients with unresectable metastases to determine the relative expression levels of both nc886 and PKR by qPCR, as well as the location of PKR by immunohistochemistry in tumour samples and healthy tissues (plasma and colon epithelium). As primary end point, the expression levels were related to the objective response to first-line chemotherapy following the response evaluation criteria in solid tumours (RECIST) and, as the second end point, with survival at 18 and 36 months. Hierarchical agglomerative clustering was performed to accommodate the heterogeneity and complexity of oncological patients' data. High expression levels of nc886 were related to the response to treatment and allowed to identify clusters of patients. Although the PKR mRNA expression was not associated with chemotherapy response, the absence of PKR location in the nucleolus was correlated with first-line chemotherapy response. Moreover, a relationship between survival and the expression of both PKR and nc886 in healthy tissues was found. Therefore, this work evaluated the best way to analyse the potential biomarkers PKR and nc886 in order to establish clusters of patients depending on the cancer outcomes using algorithms for complex and heterogeneous data.

Objectives: To examine gender differences on specific protective factors (PF: acceptance and resilience), vulnerability factors (VF: anger, depression, and anxiety; adherence to treatment and quality of life (QoL) in cardiovascular patients, as well as to study separately the relationships of these factors with adherence and QoL in females and males., Design: Observational and cross-sectional., Setting: Two Primary Care Centres in Gran Canaria., Participants: One hundred and ninety-eight cardiovascular patients (91 males and 107 females) participated., Main Measurements: Acceptance was assessed by the ICQ scale; resilience by the CD-RISC; depression by the PHQ-9; anxiety by the HADS; Anger-In and Anger-Out by the STAXI-2; QoL by the SF-36; and adherence by a self-reported scale., Results: Females exhibited higher anxiety (95% CI: 6.3-7.9) and adherence to reducing smoking (95% CI: 9.4-10.0) and drinking (95% CI: 9.6-10.1), and lower Anger-Out (95% CI: 8.9-10.0), mental QoL (95% CI: 47.0-51.3) and adherence to medication (95% CI: 22.2-23.3) compared to males. Acceptance was associated with better adherence only in women. There were more VF related to worse adherence in males. Anxiety had a negative impact on adherence, and QoL was positively associated with PF, and negatively with VF in both groups., Conclusions: Gender differences in QoL, some VF, and adherence are observed, in addition to the beneficial role of Acceptance in women., (Copyright © 2018 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Gliomas are neoplasms with high recurrence and mortality. Due to the difficulty to apply the World Health Organization (2016) classification, developing countries continue to use histological evaluation to diagnose and classify these neoplasms., Objective: To develop a semi-quantitative scale to numerically grade gliomas by its morphological characteristics., Method: A cohort of patients with gliomas was assessed and followed for 36 months. Tumor tissue sections were analyzed and graded, including aspects such as cell line, cellularity, nuclear pleomorphism, mitosis, endothelial hyperplasia, hypoxic changes, apoptotic bodies, necrosis, hemorrhage and proliferation index., Results: 58 cases were analyzed. Low-grade gliomas median score was 12 points (9 and 13.5 for percentiles 25 and 75, respectively), whereas for high-grade gliomas it was 17 points (16 and 20.5 for percentiles 25 and 75, respectively) (p < 0.0001). Thirty-six-month survival of patients with low (13/17) and high grade gliomas (6/41) was also significantly different (p < 0.0001)., Conclusions: The semi-quantitative morphological scale allows an objective evaluation of gliomas, with an adequate correlation between the score, tumor grade and survival time., (Copyright: © 2019 Permanyer.)

Introduction: Gliomas are neoplasms with high recurrence and mortality. Due to the difficulty to apply the World Health Organization (2016) classification, developing countries continue to use histological evaluation to diagnose and classify these neoplasms., Objective: To develop a semi-quantitative scale to numerically grade gliomas morphological characteristics., Method: A cohort of patients with gliomas was assessed and followed for 36 months. Tumor tissue sections were analyzed and graded, including aspects such as cell line, cellularity, nuclear pleomorphism, mitosis, endothelial hyperplasia, hypoxic changes, apoptotic bodies, necrosis, hemorrhage and proliferation index., Results: 58 cases were analyzed. Low-grade gliomas median score was 12 points (9 and 13.5 for percentiles 25 and 75, respectively), whereas for high-grade gliomas it was 17 points (16 and 20.5 for percentiles 25 and 75, respectively) (p < 0.0001). Thirty-six-month survival of patients with low (13/17) and high grade gliomas (6/41) was also significantly different (p < 0.0001)., Conclusions: The semi-quantitative morphological scale allows an objective evaluation of gliomas, with an adequate correlation between the score, tumor grade and survival time., (Copyright: © 2019 Permanyer.)

Study Question: Are serum polyunsaturated fatty acids (PUFA) concentrations, including omega-3 (ω3-PUFA) and omega-6 (ω6-PUFA), related to ART outcomes?, Summary Answer: Serum levels of long-chain ω3-PUFA were positively associated with probability of live birth among women undergoing ART., What Is Known Already: Intake of ω3-PUFA improves oocyte and embryo quality in animal and human studies. However, a recent cohort study found no relation between circulating ω3-PUFA levels and pregnancy rates after ART., Study Design Size, and Duration: This analysis included a random sample of 100 women from a prospective cohort study (EARTH) at the Massachusetts General Hospital Fertility Center who underwent 136 ART cycles within one year of blood collection., Participants/materials, Setting, Methods: Serum fatty acids (expressed as percentage of total fatty acids) were measured by gas chromatography in samples taken between Days 3 and 9 of a stimulated cycle. Primary outcomes included the probability of implantation, clinical pregnancy and live birth per initiated cycle. Cluster-weighted generalized estimating equation (GEE) models were used to analyze the association of total and specific PUFAs with ART outcomes adjusting for age, body mass index, smoking status, physical activity, use of multivitamins and history of live birth., Main Results and Role of Chance: The median [25th, 75th percentile] serum level of ω3-PUFA was 4.7% [3.8%, 5.8%] of total fatty acids. Higher levels of serum long-chain ω3-PUFA were associated with higher probability of clinical pregnancy and live birth. Specifically, after multivariable adjustment, the probability of clinical pregnancy and live birth increased by 8% (4%, 11%) and 8% (95% CI: 1%, 16%), respectively, for every 1% increase in serum long-chain ω3-PUFA levels. Intake of long-chain ω3-PUFA was also associated with a higher probability of life birth in these women, with RR of 2.37 (95% CI: 1.02, 5.51) when replacing 1% energy of long-chain ω3-PUFA for 1% energy of saturated fatty acids. Serum ω6-PUFA, ratios of ω6 and ω3-PUFA, and total PUFA were not associated with ART outcomes., Limitations Reasons for Caution: The generalizability of the findings to populations not undergoing infertility treatment may be limited. The use of a single measurement of serum fatty acids to characterize exposure may lead to potential misclassification during follow up., Wider Implications of the Findings: Serum ω3-PUFA are considered biomarkers of dietary intake. The association of higher serum long chain ω3-PUFA levels with improved ART outcomes suggests that increased intake of these fats be may be beneficial for women undergoing infertility treatment with ART., Study Funding/competing Interests: NIH grants R01-ES009718 from the National Institute of Environmental Health Sciences, P30-DK046200 and T32-DK007703-16 from the National Institute of Diabetes and Digestive and Kidney Diseases, and L50-HD085359 from the National Institute of Child Health and Human Development, and the Early Life Nutrition Fund from Danone Nutricia US. Dr Rueda is involved in a patent 9,295,662, methods for enhancing, improving, or increasing fertility or reproductive function (http://patents.com/us-9295662.html). This patent, however, does not lead to financial gain for Dr Rueda, or for Massachusetts General Hospital. Dr Rueda does not own any part of the company nor does he have any equity in any fertility related company. As Dr Rueda is not a physician, he does not evaluate patients or prescribe medications. All other coauthors have no conflicts of interest to declare., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com)

Molecular diagnosis of patients with von Willebrand disease is pending in most populations due to the complexity and high cost of conventional molecular analyses. The need for molecular and clinical characterization of von Willebrand disease in Spain prompted the creation of a multicenter project (PCM-EVW-ES) that resulted in the largest prospective cohort study of patients with all types of von Willebrand disease. Molecular analysis of relevant regions of the VWF , including intronic and promoter regions, was achieved in the 556 individuals recruited via the development of a simple, innovative, relatively low-cost protocol based on microfluidic technology and next-generation sequencing. A total of 704 variants (237 different) were identified along VWF , 155 of which had not been previously recorded in the international mutation database. The potential pathogenic effect of these variants was assessed by in silico analysis. Furthermore, four short tandem repeats were analyzed in order to evaluate the ancestral origin of recurrent mutations. The outcome of genetic analysis allowed for the reclassification of 110 patients, identification of 37 asymptomatic carriers (important for genetic counseling) and re-inclusion of 43 patients previously excluded by phenotyping results. In total, 480 patients were definitively diagnosed. Candidate mutations were identified in all patients except 13 type 1 von Willebrand disease, yielding a high genotype-phenotype correlation. Our data reinforce the capital importance and usefulness of genetics in von Willebrand disease diagnostics. The progressive implementation of molecular study as the first-line test for routine diagnosis of this condition will lead to increasingly more personalized and effective care for this patient population., (Copyright© 2017 Ferrata Storti Foundation.)

Benefit finding (BF) is defined as the individual's perception of positive change as a result of coping with an adverse life event. The beneficial effects of BF on well-being could be because BF favors the improvement of resources like self-efficacy, social support and effective coping. The main objective of this longitudinal 8 week study was to explore, in a sample of cardiac patients (n = 51), the combined contribution of BF and these resources to the positive affect. Moreover, we wanted to check whether these resources were derived from BF or, on the contrary, these resources were antecedents of BF. Results showed that after controlling for functional capacity, only effective coping could predict the positive affect at Time 1 (β = .32, p < .05), while the BF predicted it at Time 2 (β = .23, p < .001). Only social support predicted BF (β = .26, p < .05), but not the opposite. We discussed the desirability of promoting these processes to improve the emotional state of cardiac patients.

This study investigated the specific association of stressful life events (SLE) and experiential avoidance (EA) with depression in patients with mental disorders. It also analyzed the possible mediating role of depression in the relation of EA to well-being and life satisfaction. A total of 147 patients (mean age = 40.16 years) diagnosed with anxiety, mood or adjustment disorder were recruited from a mental health centre. They completed measures of SLE, EA, depression, well-being and life satisfaction. Regression analyses showed that SLE and EA were positively related to depression (R 2 = .45), although the contribution made by EA was higher (β = .61, p < .001) than the one made by SLE (β = .19, p < .01). Bootstrap mediation analyses revealed that there was an indirect effect from EA to physical well-being (B = -4.52, SE = .70, p < .001, 95% CI [-6.03, -3.20]) and satisfaction (B = -.14, SE = .02, p < .001, 95%, CI [-.19 -.09]) through depression. This indirect effect was less consistently supported with respect to emotional well-being (B = -3.33, SE = .48, p < .001, 95%, CI [-4.30, -2.41]). These findings give support to the hypothesis that EA could be an important factor contributing to depression in patients with mental disorders. The results also provide evidence that depression seems to play an important mediational role when considering the negative impact that EA exerts on patients´ well-being and satisfaction.

Early and accurate diagnosis of invasive aspergillosis (IA) is one of the most critical steps needed to efficiently treat the infection and reduce the high mortality rates that can occur. We have previously found that the Aspergillus spp. secondary metabolite, bis(methylthio)gliotoxin (bmGT), can be detected in the serum from patients with possible/probable IA. Thus, it could be used as a diagnosis marker of the infection. However, there is no data available concerning the sensitivity, specificity and performance of bmGT to detect the infection. Here, we have performed a prospective study comparing bmGT detection with galactomannan (GM), the most frequently used and adopted approach for IA diagnosis, in 357 sera from 90 episodes of patients at risk of IA. Our results, involving 79 patients that finally met inclusion criteria, suggest that bmGT presents higher sensitivity and positive predictive value (PPV) than GM and similar specificity and negative predictive value (NPV). Importantly, the combination of GM and bmGT increased the PPV (100 %) and NPV (97.5 %) of the individual biomarkers, demonstrating its potential utility in empirical antifungal treatment guidance and withdrawal. These results indicate that bmGT could be a good biomarker candidate for IA diagnosis and, in combination with GM, could result in highly specific diagnosis of IA and management of patients at risk of infection.

The diagnosis of von Willebrand disease (VWD) remains difficult in a significant proportion of patients. A Spanish multicentre study investigated a cohort of 556 patients from 330 families who were analysed centrally. VWD was confirmed in 480. Next generation sequencing (NGS) of the whole coding VWF was carried out in all recruited patients, compared with the phenotype, and a final diagnosis established. A total of 238 different VWF mutations were found, 154 were not included in the Leiden Open Variation Database (LOVD). Of the patients, 463 were found to have VWF mutation/s. A good phenotypic/genotypic association was estimated in 96.5% of the patients. One hundred seventy-four patients had two or more mutations. Occasionally a predominant phenotype masked the presence of a second abnormality. One hundred sixteen patients presented with mutations that had previously been associated with increased von Willebrand factor (VWF) clearance. RIPA unavailability, central phenotypic results disagreement and difficult distinction between severe type 1 and type 3 VWD prevented a clear diagnosis in 70 patients. The NGS study facilitated an appropriate classification in 63 of them. The remaining seven patients presented with a VWF novel mutation pending further investigation. In five patients with a type 3 and two with a type 2A or 2B phenotype with no mutation, an acquired von Willebrand syndrome (AVWS) was suspected/confirmed. These data seem to support NGS as a first line efficient and faster paradigm in VWD diagnosis.

Background: The use of information and communication technologies (ICTs) in the health service is increasing. In spite of limitations, such as lack of time and experience, the deployment of ICTs in the healthcare system has advantages which include patient satisfaction with secure messaging, and time saving benefits and utility for patients and health professionals. ICTs may be helpful as either interventions on their own or as complementary tools to help patients stop smoking., Objectives: To gather opinions from both medical professionals and smokers about an email-based application that had been designed by our research group to help smoking cessation, and identify the advantages and disadvantages associated with interventions based on the utilization of ICTs for this purpose., Methods: A qualitative, descriptive-interpretative study with a phenomenological perspective was performed to identify and interpret the discourses of the participating smokers and primary healthcare professionals. Data were obtained through two techniques: semi-structured individual interviews and discussion groups, which were recorded and later systematically and literally transcribed together with the interviewer's notes. Data were analyzed with the ATLAS TI 6.0 programme., Results: Seven individual interviews and four focal groups were conducted. The advantages of the application based on the email intervention designed by our research group were said to be the saving of time in consultations and ease of access for patients who found work timetables and following a programme for smoking cessation incompatible. The disadvantages were thought to be a lack of personal contact with the healthcare professional, and the possibility of cheating/ self-deception, and a greater probability of relapse on the part of the smokers., Conclusions: Both patients and healthcare professionals viewed the email-based application to help patients stop smoking as a complementary aid to face-to-face consultations. Nevertheless, ICTs could not substitute personal contact in the smoking cessation programme.

Background: Common interventions for smoking cessation are based on medical advice and pharmacological aid. Information and communication technologies may be helpful as interventions by themselves or as complementary tools to quit smoking. The objective of the study was to determine the use of information and communication technologies (ICTs) in the smoking population attended in primary care, and describe the major factors associated with its use., Methods: Descriptive observational study in 84 health centres in Cataluña, Aragon and Salamanca. We included by simple random sampling 1725 primary healthcare smokers (any amount of tobacco) aged 18-85. Through personal interview professionals collected Socio-demographic data and variables related with tobacco consumption and ICTs use were collected through face to face interviews Factors associated with the use of ICTs were analyzed by logistic regression., Results: Users of at least one ICT were predominantly male, young (18-45 years), from most favoured social classes and of higher education. Compared with non-ICTs users, users declared lower consumption of tobacco, younger onset age, and lower nicotine dependence. The percentages of use of email, text messages and web pages were 65.3%, 74.0% and 71.5%, respectively. Factors associated with the use of ICTs were age, social class, educational level and nicotine dependence level. The factor most closely associated with the use of all three ICTs was age; mainly individuals aged 18-24., Conclusions: The use of ICTs to quit smoking is promising, with the technology of mobile phones having a broader potential. Younger and more educated subjects are good targets for ICTs interventions on smoking cessation.

Objective: In the following study, we observe the progress of various invasive calculi treatments that have taken place in our hospital in the last 15 years., Material and Method: We extracted data from our hospital database on patients who underwent extracorporeal shock wave lithotripsy (ESWL), endoscopic surgery and open surgery. We analyzed how the incidence of these treatments has evolved over the last 15 years. We also studied the number of publications in PubMed that reference invasive calculi treatments., Results: From January 1998 to December 2012, a total of 10,947 patients were treated instrumentally for lithiasis, 9,695 of whom (90.4%) underwent ESWL and 1,034 of whom underwent endoscopic or open surgery (9.6%). The incidence of lithotripsy treatments reached its maximum in 2006, with a progressive reduction thereafter. The incidence of endoscopic surgery increased progressively until 2009 and then leveled off. We can see how in recent years there has been a clear increase in the number of studies that have covered endoscopic surgery, with a decreasing number covering ESWL., Conclusions: In our community, ESWL remains the most widely used invasive treatment for calculi. In recent years, there has been a reduction in the number of ESWL treatments and an increase in the number of endoscopic treatments, with open surgery showing a clearly decreasing trend., (Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)

Ovarian cancers are thought to result from the accumulation of multiple genetic aberrations that transform ovarian and/or fallopian tube surface epithelial cells, allowing for their abnormal growth, proliferation and metastasis. In the report presented here, we carried out genome-wide copy-number analysis using comparative genomic hybridization on a panel of mouse ovarian cancer (OVCA) cell lines previously established in our laboratory. We identified a recurrent focal amplification on mouse chromosomal region 2qB, which contains the LIM-homeodomain-containing transcription factor 1B (Lmx1b) gene. LMX1B is not expressed in normal human ovary, but is expressed in many human OVCA cell lines and primary tumors. High expression of LMX1B correlates with poor outcome. To clarify the role of LMX1B in ovarian carcinogenesis, we transduced LMX1B into a panel of mouse and human OVCA cell lines and demonstrated that LMX1B strongly promotes migration of cancer cells in culture and promotes xenograft growth in nude mice. Conversely, knockdown of LMX1B in a human cell line with endogenous high expression of LMX1B inhibits cell migration in vitro and tumor growth in vivo. Microarray analysis of cells overexpressing LMX1B identified the nuclear factor (NF)-κB pathway as a potential mediator of tumor progression and subsequent treatment of NFκB inhibitor decreased the migratory capacity of these cells. Thus, our data demonstrate that LMX1B is a novel oncogene in OVCA pathogenesis.

In many human cancers, the tumor suppressor, p27(kip1) (p27), a cyclin-dependent kinase inhibitor critical to cell cycle arrest, undergoes perpetual ubiquitin-mediated proteasomal degradation by the E3 ligase complex SCF-Skp2/Cks1 and/or cytoplasmic mislocalization. Lack of nuclear p27 causes aberrant cell cycle progression, and cytoplasmic p27 mediates cell migration/metastasis. We previously showed that mitogenic 17-β-estradiol (E2) induces degradation of p27 by the E3 ligase Skp1-Cullin1-F-Box- S phase kinase-associated protein2/cyclin dependent kinase regulatory subunit 1 in primary endometrial epithelial cells and endometrial carcinoma (ECA) cell lines, suggesting a pathogenic mechanism for type I ECA, an E2-induced cancer. The current studies show that treatment of endometrial carcinoma cells-1 (ECC-1) with small molecule inhibitors of Skp2/Cks1 E3 ligase activity (Skp2E3LIs) stabilizes p27 in the nucleus, decreases p27 in the cytoplasm, and prevents E2-induced proliferation and degradation of p27 in endometrial carcinoma cells-1 and primary ECA cells. Furthermore, Skp2E3LIs increase p27 half-life by 6 hours, inhibit cell proliferation (IC50, 14.3μM), block retinoblastoma protein (pRB) phosphorylation, induce G1 phase block, and are not cytotoxic. Similarly, using super resolution fluorescence localization microscopy and quantification, Skp2E3LIs increase p27 protein in the nucleus by 1.8-fold. In vivo, injection of Skp2E3LIs significantly increases nuclear p27 and reduces proliferation of endometrial epithelial cells by 42%-62% in ovariectomized E2-primed mice. Skp2E3LIs are specific inhibitors of proteolytic degradation that pharmacologically target the binding interaction between the E3 ligase, SCF-Skp2/Cks1, and p27 to stabilize nuclear p27 and prevent cell cycle progression. These targeted inhibitors have the potential to be an important therapeutic advance over general proteasome inhibitors for cancers characterized by SCF-Skp2/Cks1-mediated destruction of nuclear p27.

This study examined whether depressive symptoms mediated the association between coping strategies and quality of life (QoL) in a sample of hypertensive patients, and the prospective contribution of depressive symptoms and coping strategies in the prediction of their QoL. One hundred and fifty patients (50% males and 50% females) with a diagnosis of essential hypertension were recruited from a general hospital. Symptoms of depression, coping and QoL measures (global score and dimensions) were collected at baseline. Sixty-three participants completed the QoL questionnaire again one year later (T2). The results indicated that the relations between emotion coping and QoL (global score, satisfaction and social support) were totally mediated by depressive symptoms. The association between emotion coping and well-being was, however, partially mediated by depressive symptoms. Furthermore, only baseline instrumental coping strategies predicted higher levels of QoL (global score, well-being and social support) at T2. Neither emotion coping nor depressive symptoms were significantly associated with prospective QoL. These findings suggest that depressive symptoms may be a mechanism linking the manner in which patients cope with their hypertension and their QoL. They also emphasise the adaptive role played by instrumental coping responses in the management of hypertension in the long term.

Introduction: The classic treatment of Zenker's diverticulum (ZD) has been cricopharyngeal myotomy (CPM), with the need or not to resect it being argued (diverticulectomy versus diverticulopexy). However, the advance of endoscopic techniques requires new treatment strategies to be established. We analyse the complications and clinical results of our series with cricopharyngeal myotomy and diverticulectomy in patients with ZD., Method: A retrospective, observational and descriptive study was conducted on 33 patients who, between January 1998 and December 2010, had a diverticulectomy and CPM performed in the university hospitals Virgen del Rocío in Seville and Carlos Haya in Malaga. Demographic and operative variables that might be associated with morbidity were analyzed., Results: Seventeen patients were treated in the Carlos Haya Hospital, Málaga and sixteen in the Virgen del Rocío Hospital, Seville. Although there were no deaths, the morbidity rate of the series was 27% (9 cases), all associated with an oesophageal-cutaneous fistula. None of the variables studied were significantly associated with the appearance of morbidity. None of the patients had a clinical or radiological recurrence of ZD after a mean follow up of 44 months (range, 6 -192)., Conclusions: Diverticulectomy combined with CPM is a good technique for the treatment of ZD, with excellent clinical and functional results in the medium to long term, despite the high morbidity in the form of an oesophageal-cutaneous fistula., (Copyright © 2011 AEC. Published by Elsevier Espana. All rights reserved.)

Objective: During the first pandemic, some patients with pandemic (H1N1) 2009 influenza were treated with corticosteroids. The objective of this study was to assess the effect on survival of corticosteroid therapy in patients with pandemic (H1N1) 2009 influenza., Methods: Prospective, observational, multicenter study performed in 148 ICU. Data were recorded in the GTEI/SEMICYUC registry. Adult patients with pandemic (H1N1) 2009 influenza confirmed by rt-PCR were included in the analysis. Database records specified corticosteroid type and reason for corticosteroid treatment., Results: 372 patients with the diagnosis of primary viral pneumonia and completed outcomes treated in an ICU were included in the database. Mechanical ventilation was used in 70.2% of the patients. 136 (36.6%) patients received corticosteroids after a diagnosis of primary viral pneumonia. Obesity (35.6% vs 47.8% p = 0.021) and asthma (7.6% vs 15.4% p = 0.018), were more frequent in the group treated with corticosteroids. A Cox regression analysis adjusted for severity and potential confounding factors found that the use of corticosteroid therapy was not significantly associated with mortality (HR = 1.06, 95% CI 0.626-1.801; p = 0.825)., Conclusions: Corticosteroid therapy in a selected group of patients with primary viral pneumonia due to pandemic (H1N1) 2009 influenza does not improve survival., (Copyright © 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate whether polymorphisms in Toll-like receptor (TLR) genes, previously reported to be associated with immune-mediated diseases, are involved in systemic sclerosis (SSc)., Methods: We genotyped 14 polymorphisms in the genes for TLRs 2, 4, 7, 8, and 9 in a discovery cohort comprising 452 SSc patients and 537 controls and a replication cohort consisting of 1,170 SSc patients and 925 controls. In addition, we analyzed 15-year followup data on 964 patients to assess the potential association of TLR variants with the development of disease complications. We analyzed the functional impact of the associated polymorphism on monocyte-derived dendritic cells., Results: In the discovery cohort, we observed that a rare functional polymorphism in TLR2 (Pro631His) was associated with antitopoisomerase (antitopo) positivity (odds ratio 2.24 [95% confidence interval 1.24-4.04], P=0.003). This observation was validated in the replication cohort (odds ratio 2.73 [95% confidence interval 1.85-4.04], P=0.0001). In addition, in the replication cohort the TLR2 variant was associated with the diffuse subtype of the disease (P=0.02) and with the development of pulmonary arterial hypertension (PAH) (Cox proportional hazards ratio 5.61 [95% confidence interval 1.53-20.58], P=0.003 by log rank test). Functional analysis revealed that monocyte-derived dendritic cells carrying the Pro63His variant produced increased levels of inflammatory mediators (tumor necrosis factor α and interleukin-6) upon TLR-2-mediated stimulation (both P<0.0001)., Conclusion: Among patients with SSc, the rare TLR2 Pro631His variant is robustly associated with antitopoisomerase positivity, the diffuse form of the disease, and the development of PAH. In addition, this variant influences TLR-2-mediated cell responses. Further research is needed to elucidate the precise role of TLR-2 in the pathogenesis of SSc., (Copyright © 2012 by the American College of Rheumatology.)

Background: The number of copies of the HLA-DRB1 shared epitope, and the minor alleles of the STAT4 rs7574865 and the PTPN22 rs2476601 polymorphisms have all been linked with an increased risk of developing rheumatoid arthritis. In the present study, we investigated the effects of these genetic variants on disease activity and disability in patients with early arthritis., Methodology and Results: We studied 640 patients with early arthritis (76% women; median age, 52 years), recording disease-related variables every 6 months during a 2-year follow-up. HLA-DRB1 alleles were determined by PCR-SSO, while rs7574865 and rs2476601 were genotyped with the Taqman 5' allelic discrimination assay. Multivariate analysis was performed using generalized estimating equations for repeated measures. After adjusting for confounding variables such as gender, age and ACPA, the TT genotype of rs7574865 in STAT4 was associated with increased disease activity (DAS28) as compared with the GG genotype (β coefficient [95% confidence interval] = 0.42 [0.01-0.83], p = 0.044). Conversely, the presence of the T allele of rs2476601 in PTPN22 was associated with diminished disease activity during follow-up in a dose-dependent manner (CT genotype = -0.27 [-0.56- -0.01], p = 0.042; TT genotype = -0.68 [-1.64- -0.27], p = 0.162). After adjustment for gender, age and disease activity, homozygosity for the T allele of rs7574865 in STAT4 was associated with greater disability as compared with the GG genotype., Conclusions: Our data suggest that patients with early arthritis who are homozygous for the T allele of rs7574865 in STAT4 may develop a more severe form of the disease with increased disease activity and disability.

Objective: To determine the role of Class II HLAs in SSc patients from Italy and Spain and in SSc patients of Caucasian ancestry., Methods: Nine hundred and forty-four SSc patients (Italy 392 patients; Spain 452 patients) and 1320 ethnically matched healthy controls (Italy 398 patients; Spain 922 patients) were genotyped up to the fourth digit by PCR with sequence-specific oligonucleotides for HLA-DRB1, DQA1 and DQB1 loci. Patients included 390 ACA-positive and 254 anti-topo I-positive subjects. Associations between SSc or SSc-specific antibodies and HLA alleles or HLA haplotypes were sought via the chi-square test after 10 000-fold permutation testing. A meta-analysis including this study cohort and other Caucasoids samples was also conducted., Results: In both the cohorts, the strongest association was observed between the HLA-DRB1*1104 allele and SSc or anti-topo I antibodies. The HLA-DRB1*1104 -DQA1*0501 -DQB1*0301 haplotype was overrepresented in Italian [odds ratio (OR) = 2.069, 95% asymptotic CIs (CI(95)) 1.486, 2.881; P < 0.001] and in Spanish patients (OR = 6.707, CI(95) 3.974, 11.319; P < 0.001) as well as in anti-topo-positive patients: Italy (OR = 2.642, CI(95) 1.78, 3.924; P < 0.001) and Spain (OR = 20.625, CI(95) 11.536, 36.876; P < 0.001). In both the populations we also identified an additional risk allele (HLA-DQB1*03) and a protective allele (HLA-DQB1*0501) in anti-topo-positive patients. The meta-analysis showed different statistically significant associations, the most interesting being the differential association between HLA-DRB1*01 alleles and ACAs (OR = 1.724, CI(95) 1.482, 2.005; P < 0.001) or topo I antibodies (OR = 0.5, CI(95) 0.384, 0.651; P < 0.001)., Conclusions: We describe multiple robust associations between SSc and HLA Class II antigens in Caucasoids that may help to understand the genetic architecture of SSc.

The relationships between anger expression (in, out, and control) and cardiovascular health (emotional distress, cardiovascular symptoms reported, and preventive health behaviors) were analyzed in 327 women (range 17-60 years). The same criteria (N= 218), as well as blood pressure (BP) registered in medical checkups (N= 90) were recorded one year later. Four groups according to anger-in and anger-control scores, going from the most hostile (high anger-in and low anger-control) to the least hostile (low anger-in and high anger-control) were considered. The results indicated that the most hostile group, with the least adaptive anger expression, presented worst cardiovascular health than the other three groups, at both temporal moments. Furthermore, the presence of women with pathological BP levels was higher in the groups of high anger-in. These data ratify the role of anger expression, especially its repression (anger-in) and the lack of adequate canalization or control in women's cardiovascular health from a prospective design. Appropriate management of anger feelings and the practice of preventive health behaviors can protect women from cardiovascular problems.

Objectives: The aim of this study was to confirm the implication of macrophage migration inhibitory factor (MIF) gene in SSc susceptibility or clinical phenotypes in a large European population., Methods: A total of 3800 SSc patients and 4282 healthy controls of white Caucasian ancestry from eight different European countries were included in the study. The MIF -173 single nucleotide polymorphism (SNP) was selected as genetic marker and genotyped using Taqman 5' allelic discrimination assay., Results: The MIF -173 SNP showed association with SSc [P = 0.04, odds ratio (OR) = 1.10, 95% CI 1.00, 1.19]. Analysis of the MIF -173 polymorphism according to SSc clinical phenotype revealed that the frequency of the -173*C allele was significantly higher in the dcSSc group compared with controls (P = 5.30E-03, OR = 1.21, 95% CI 1.07, 1.38). Conversely, the frequency of the MIF -173*C allele was significantly underrepresented in the lcSSc group compared with dcSSc patients, supporting previous findings [(P = 0.04, OR = 0.86, 95% CI 0.75, 0.99); meta-analysis including previous results (P = 0.005, OR = 0.83, 95% CI 0.73, 0.94)]., Conclusion: Our results confirm the role of MIF -173 promoter polymorphism in SSc, and provide evidence of a strong association with the dcSSc subgroup of patients. Hence, the MIF -173 variant is confirmed as a promising clinical phenotype genetic marker.

The aim of this study was to determine, through a genome-wide association study (GWAS), the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc). We considered limited (lcSSc) and diffuse (dcSSc) cutaneous involvement, and the relationships with presence of the SSc-specific auto-antibodies, anti-centromere (ACA), and anti-topoisomerase I (ATA). Four GWAS cohorts, comprising 2,296 SSc patients and 5,171 healthy controls, were meta-analyzed looking for associations in the selected subgroups. Eighteen polymorphisms were further tested in nine independent cohorts comprising an additional 3,175 SSc patients and 4,971 controls. Conditional analysis for associated SNPs in the HLA region was performed to explore their independent association in antibody subgroups. Overall analysis showed that non-HLA polymorphism rs11642873 in IRF8 gene to be associated at GWAS level with lcSSc (P = 2.32×10(-12), OR = 0.75). Also, rs12540874 in GRB10 gene (P = 1.27 × 10(-6), OR = 1.15) and rs11047102 in SOX5 gene (P = 1.39×10(-7), OR = 1.36) showed a suggestive association with lcSSc and ACA subgroups respectively. In the HLA region, we observed highly associated allelic combinations in the HLA-DQB1 locus with ACA (P = 1.79×10(-61), OR = 2.48), in the HLA-DPA1/B1 loci with ATA (P = 4.57×10(-76), OR = 8.84), and in NOTCH4 with ACA P = 8.84×10(-21), OR = 0.55) and ATA (P = 1.14×10(-8), OR = 0.54). We have identified three new non-HLA genes (IRF8, GRB10, and SOX5) associated with SSc clinical and auto-antibody subgroups. Within the HLA region, HLA-DQB1, HLA-DPA1/B1, and NOTCH4 associations with SSc are likely confined to specific auto-antibodies. These data emphasize the differential genetic components of subphenotypes of SSc., Competing Interests: The authors have declared that no competing interests exist.

Fifty-two men who had suffered a first episode ischemic heart disease reported their degree of life satisfaction, the strategies they used to adjust to the illness, and the symptoms of anxiety and depression they felt. The multiple regression analyses carried out indicated that emotional distress was associated with a lower level of life satisfaction. In the analyses of anxiety symptoms, the use of negative adjustment strategies was also a significant predictor. Lastly, a significant Life Satisfaction x Type of Adjustment interaction was obtained. According to this, the patients who felt more satisfaction with their lives used more positive strategies to adjust to the illness and fewer negative ones, than the group of patients who were less satisfied. In conclusion, life satisfaction predicts emotional wellbeing of patients with ischemic heart disease and it enhances the implementation of appropriate strategies to cope with the disease. Moreover, although life satisfaction has been considered a stable measure, we suggest it may change as the experience of illness limits individuals' important goals.

Objectives: The aim of this study was to confirm the influence of TNFSF4 polymorphisms on systemic sclerosis (SSc) susceptibility and phenotypic features., Methods: A total of 8 European populations of Caucasian ancestry were included, comprising 3014 patients with SSc and 3125 healthy controls. Four genetic variants of TNFSF4 gene promoter (rs1234314, rs844644, rs844648 and rs12039904) were selected as genetic markers., Results: A pooled analysis revealed the association of rs1234314 and rs12039904 polymorphisms with SSc (OR 1.15, 95% CI 1.02 to 1.31; OR 1.18, 95% CI 1.08 to 1.29, respectively). Significant association of the four tested variants with patients with limited cutaneous SSc (lcSSc) was revealed (rs1234314 OR 1.22, 95% CI 1.07 to 1.38; rs844644 OR 0.91, 95% CI 0.83 to 0.99; rs844648 OR 1.10, 95% CI 1.01 to 1.20 and rs12039904 OR 1.20, 95% CI 1.09 to 1.33). Association of rs1234314, rs844648 and rs12039904 minor alleles with patients positive for anti-centromere antibodies (ACA) remained significant (OR 1.23, 95% CI 1.10 to 1.37; OR 1.12, 95% CI 1.01 to 1.25; OR 1.22, 95% CI 1.07 to 1.38, respectively). Haplotype analysis confirmed a protective haplotype associated with SSc, lcSSc and ACA positive subgroups (OR 0.88, 95% CI 0.82 to 0.96; OR 0.88, 95% CI 0.80 to 0.96; OR 0.86, 95% CI 0.77 to 0.97, respectively) and revealed a new risk haplotype associated with the same groups of patients (OR 1.14, 95% CI 1.03 to 1.26; OR 1.20, 95% CI 1.08 to 1.35; OR 1.23, 95% CI 1.07 to 1.42, respectively)., Conclusions: The data confirm the influence of TNFSF4 polymorphisms in SSc genetic susceptibility, especially in subsets of patients positive for lcSSc and ACA.

Background: Public data integration may help overcome challenges in clinical implementation of microarray profiles. We integrated several ovarian cancer datasets to identify a reproducible predictor of survival., Methodology/principal Findings: Four microarray datasets from different institutions comprising 265 advanced stage tumors were uniformly reprocessed into a single training dataset, also adjusting for inter-laboratory variation ("batch-effect"). Supervised principal component survival analysis was employed to identify prognostic models. Models were independently validated in a 61-patient cohort using a custom array genechip and a publicly available 229-array dataset. Molecular correspondence of high- and low-risk outcome groups between training and validation datasets was demonstrated using Subclass Mapping. Previously established molecular phenotypes in the 2(nd) validation set were correlated with high and low-risk outcome groups. Functional representational and pathway analysis was used to explore gene networks associated with high and low risk phenotypes. A 19-gene model showed optimal performance in the training set (median OS 31 and 78 months, p < 0.01), 1(st) validation set (median OS 32 months versus not-yet-reached, p = 0.026) and 2(nd) validation set (median OS 43 versus 61 months, p = 0.013) maintaining independent prognostic power in multivariate analysis. There was strong molecular correspondence of the respective high- and low-risk tumors between training and 1(st) validation set. Low and high-risk tumors were enriched for favorable and unfavorable molecular subtypes and pathways, previously defined in the public 2(nd) validation set., Conclusions/significance: Integration of previously generated cancer microarray datasets may lead to robust and widely applicable survival predictors. These predictors are not simply a compilation of prognostic genes but appear to track true molecular phenotypes of good- and poor-outcome.

Objective: To investigate the role of the Fc(α)RI 844 A>G functional polymorphism in the genetic predisposition to rheumatoid arthritis (RA) and systemic sclerosis (SSc) susceptibility., Methods: The study population was composed of 1401 patients with SSc, 642 patients with RA, and 1317 healthy controls. The Fc(α)RI (CD89) single-nucleotide polymorphism rs16986050 was genotyped by pyrosequencing., Results: We observed no significant deviation of the genotype and allele frequencies in RA and SSc compared to controls. A metaanalysis and a recessive and dominant model yielded similar negative results., Conclusion: Our data show that the Fc(α)RI 844 A>G polymorphism is not associated with SSc or RA susceptibility.

Objective: Two functional single nucleotide polymorphisms (SNP) in the PTPN22 gene (rs24746601 and rs33996649) have been associated with autoimmunity. The aim of this study was to investigate the role of the R263Q SNP for the first time and to re-evaluate the role of the R620W SNP in the genetic predisposition to systemic sclerosis (SSc) susceptibility and clinical phenotypes., Methods: 3422 SSc patients (2020 with limited cutaneous SSc and 1208 with diffuse cutaneous SSc) and 3638 healthy controls of Caucasian ancestry from an initial case--control set of Spain and seven additional independent replication cohorts were included in our study. Both rs33996649 and rs2476601 PTPN22 polymorphisms were genotyped by TaqMan allelic discrimination assay. A meta-analysis was performed to test the overall effect of these PTPN22 polymorphisms in SSc., Results: The meta-analysis revealed evidence of association of the rs2476601 T allele with SSc susceptibility (p(FDRcorrected)=0.03 pooled, OR 1.15, 95% CI 1.03 to 1.28). In addition, the rs2476601 T allele was significantly associated with anticentromere-positive status (p(FDRcorrected)=0.02 pooled, OR 1.22, 95% CI 1.05 to 1.42). Although the rs33996649 A allele was significantly associated with SSc in the Spanish population (p(FDRcorrected)=0.04, OR 0.58, 95% CI 0.36 to 0.92), this association was not confirmed in the meta-analysis (p=0.36 pooled, OR 0.89, 95% CI 0.72 to 1.1)., Conclusion: The study suggests that the PTPN22 R620W polymorphism influences SSc genetic susceptibility but the novel R263Q genetic variant does not. These data strengthen evidence that the R620W mutation is a common risk factor in autoimmune diseases.