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Background Kidney replacement therapy (KRT) confers the highest risk of death from coronavirus disease 2019 (COVID-19). However, most data refer to the early pandemic waves. Whole-year analysis compared with prior secular trends are scarce. Methods We present the 2020 REMER Madrid KRT registry, corresponding to the Spanish Region hardest hit by COVID-19. Results In 2020, KRT incidence decreased 12% versus 2019, while KRT prevalence decreased by 1.75% for the first time since records began and the number of kidney transplants (KTs) decreased by 16%. Mortality on KRT was 10.2% (34% higher than the mean for 2008–2019). The 2019–2020 increase in mortality was larger for KTs (+68%) than for haemodialysis (+24%) or peritoneal dialysis (+38%). The most common cause of death was infection [n = 419 (48% of deaths)], followed by cardiovascular [n = 200 (23%)]. Deaths from infection increased by 167% year over year and accounted for 95% of excess deaths in 2020 over 2019. COVID-19 was the most common cause of death (68% of infection deaths, 33% of total deaths). The bulk of COVID-19 deaths [209/285 (73%)] occurred during the first COVID-19 wave, which roughly accounted for the increased mortality in 2020. Being a KT recipient was an independent risk factor for COVID-19 death. Conclusions COVID-19 negatively impacted the incidence and prevalence of KRT, but the increase in KRT deaths was localized to the first wave of the pandemic. The increased annual mortality argues against COVID-19 accelerating the death of patients with short life expectancy and the temporal pattern of COVID-19 mortality suggests that appropriate healthcare may improve outcomes.

The tarsal navicular is an essential component of the Chopart joint and crucial for most of hindfoot motion. Most fractures are low-energy dorsal avulsions that may be treated nonoperatively. Displaced comminuted fractures require open reduction and internal fixation, sometimes with external fixation, bridge plating, and bone grafting. Diagnosis of stress fractures is commonly delayed. Conservative treatment is associated with good results, but surgery allows for quicker return-to-play in athletes. Nonunion in acute and stress fractures needs open debridement, grafting, and stable fixation. Müller-Weiss disease may present with a fragmented navicular and mimic an acute or a stress fracture.

After isolated ankle (tibiotalar) arthrodesis, the triceps progressively shifts the subtalar joint into varus thus blocking compensatory motion from the midtarsal joints. In a tibiotalocalcaneal arthrodesis, the subtalar may be fixed with the correct valgus. Comparison between ankle and tibiotalocalcaneal arthrodesis does not clearly favor one over another for pain relief, satisfaction, and gait analysis. Compensatory sagittal plane motion through the midtarsal joints when the subtalar is fixed in valgus may be responsible for these results. Tibiotalocalcaneal arthrodesis has become our procedure of choice over isolated tibiotalar for end-stage ankle arthritis regardless of the radiographic state of the subtalar.

Johnson and Strom stage I posterior tibialis tendon dysfunction presents with pain and swelling but preserved function and no deformity. Diagnosis is clinical. Pathomechanics explains the overloading of the tendon that may be worsened by a tight gastrocnemius, but systemic inflammatory disease may also be responsible for a stage I condition. Medial heel wedged orthoses are effective in most patients. Surgery usually consists of an open/endoscopic tenosynovectomy. In cases of complete tendon rupture, flexor digitorum longus tendon transfer may be considered. Stage I patients with a higher risk of progression-inflammatory conditions, excessive laxity, obese-may benefit from a "prophylactic" medializing calcaneal osteotomy.

Tibiotalocalcaneal arthrodesis (TTCA) is the most common and reliable procedure in the treatment of patients with end-stage ankle arthritis combined with severe deformity. Many of these patients present with difficult previous sequelae that include nonunion, malunion, broken implants, vascular deficiencies, skin problems, or a combination of the previous. In that complex scenario, sometimes the only alternative treatment is a below-the-knee amputation. Image studies--weightbearing X-rays, tomography, and magnetic resonance - are fundamental to evaluate alignment and bone stock. When all conservative treatments fail to alleviate pain and dysfunction, the combination of osteotomies and arthrodesis is the procedure of choice. Surgical planning needs to be very detailed and thorough with a special focus on bone loss after debridement of non-healthy tissue and removal of metalwork. TTCA with grafting allows for the preservation of the limb in more than 80% of cases but at the expense of many complications with nonunion rates of approximately 20% of cases. There is controversy about the use of a retrograde nail versus specific TTCA plate and screws but results from biomechanical studies do not show a clear superiority of one specific construct. Amputation rates are close to 5% of cases after repeated failed surgeries. Bulk allografts increase the rate of nonunions but apparently do not have an influence on postoperative infections. Valgus positioning of the ankle/hindfoot is paramount to allow for maximal sagittal plane compensation from the midtarsal joints. Most patients are satisfied with the results of these salvage operations. The studies presented in this article have a considerable wide array of different scenarios that obviously bias some of the results, complications, and outcomes but together they present a persuasive pattern toward considering TTC with grafting and nail or plate fixation as a good salvage procedure that may help the patients to maintain their foot and ankle with a better alignment, function, and pain relief.

Background Couple relationship distress is common and associated with poor physical, psychological, and relational outcomes for both partners. Emotionally Focused Therapy for couples (EFT) is a short-term structured approach based on attachment theory that integrates a humanistic, experiential approach to restructuring emotional experience and a systemic structural approach to restructuring interactions. This model has been shown to be an effective treatment for couple distress. The supporting research, however, has only been conducted with English-speaking couples. Despite Spanish being the second-most spoken language and meaningful cultural differences between English- and Spanish-speaking countries, the efficacy of EFT has not been examined in this cultural context. This study will examine the efficacy of EFT in this particular context and advance the understanding of potential mechanisms of change. Methods We will use a multicenter randomized wait-list controlled design to examine the efficacy of EFT in a Spanish-speaking sample of moderately distressed couples. One hundred forty individuals in 70 couples in Argentina, Costa Rica, Guatemala, Mexico, and Spain will be randomly assigned to receive 19–21 sessions of EFT or be placed on a waitlist. Outcomes on a range of relational and individual mental health variables will be assessed prior to random assignment, throughout treatment, and at the conclusion of treatment. Primary outcomes will include dyadic adjustment, couple satisfaction, and attachment. Secondary variables, such as loneliness, parenting, affective communication, and sexual satisfaction, will be included as potential mediators of the treatment effect. Couples in the treatment group will also be assessed at 3-, 6-, 12-, 18-, and 24-month follow-ups. Process variables such as the therapeutic alliance will also be assessed routinely in couples assigned to the treatment group. Couples in the waitlist will receive a psycho-educational program based on EFT after completing the study. Discussion This study will be the first RCT of Emotionally Focused Therapy in a Spanish-speaking context. The results of the study will inform researchers interested in whether treatments developed and tested in the USA and Canada can be effective in differing cultural contexts. It may also point researchers and clinicians to areas where cultural adaptation is needed to improve efficacy. Trial registration ClinicalTrials.gov NCT04277325. Registered on February 20, 2020

In a context of therapeutic revolution in older adults with AML, it is becoming increasingly important to select patients for the various treatment options by taking account of short-term efficacy and toxicity as well as long-term survival. Here, the data from three European registries for 1,199 AML patients aged 70 years or older treated with intensive chemotherapy were used to develop a prognostic scoring system. The median follow-up was 50.8 months. In the training set of 636 patients, age, performance status, secondary AML, leukocytosis, and cytogenetics, as well as NPM1 mutations (without FLT3-ITD), were all significantly associated with overall survival, albeit not to the same degree. These factors were used to develop a score that predicts long-term overall survival. Three risk-groups were identified: a lower, intermediate and higher-risk score with predicted 5-year overall survival (OS) probabilities of ≥12% (n = 283, 51%; median OS = 18 months), 3–12% (n = 226, 41%; median OS = 9 months) and n = 47, 8%; median OS = 3 months), respectively. This scoring system was also significantly associated with complete remission, early death and relapse-free survival; performed similarly in the external validation cohort (n = 563) and showed a lower false-positive rate than previously published scores. The European Scoring System ≥70, easy for routine calculation, predicts long-term survival in older AML patients considered for intensive chemotherapy.

Limited knowledge exists on how early host response impacts outcomes in influenza pneumonia.This study assessed what was the contribution of host immune response at the emergency department on hospital mortality amongst adults with influenza A H1N1pdm09 pneumonia and whether early stratification by immune host response anticipates the risk of death. This is a secondary analysis from a prospective, observational, multicenter cohort comparing 75 adults requiring intensive care with 38 hospitalized in medical wards. Different immune response biomarkers within 24 h of hospitalization and their association with hospital mortality were assessed.Fifty-three were discharged alive. Non-survivors were associated (plt;0.05) with lower lymphocytes (751 vs. 387), monocytes (450 vs. 220) expression of HLA-DR (1,662 vs. 962) and higher IgM levels (178 vs. 152;plt;0.01). Lymphocyte subpopulations amongst non-survivors showed a significantly (plt;0.05) lower number of TCD3+ (247.2 vs. 520.8), TCD4+ (150.3 vs. 323.6), TCD8+ (95.3 vs. 151.4) and NKCD56+ (21.9 vs. 91.4). Number of lymphocytes, monocytes and NKCD56+ predicted hospital mortality (AUC 0.854). Hospital mortality was independently associated with low HLA-DR values, low number of NKCD56+ cells, and high IgM levels, in a Cox-proportional hazard analysis. A second model, documented that hospital mortality was independently associated with a phenotype combining immunoparalysis with hyperinflammation (HR 5.53; 95%CI 2.16-14.14), after adjusting by predicted mortality.We conclude that amongst influenza pneumonia, presence of immunoparalysis was a major mortality driver. Influenza heterogeneity was partly explained by early specific host response dysregulations which should be considered to design personalized approaches of adjunctive therapy.

In cases of treatment failure in acute myeloid leukemia (AML), the utility of mutational profiling in primary refractoriness and relapse is not established. We undertook a perspective study using next-generation sequencing (NGS) of clinical follow-up samples (n=91) from 23 patients with AML with therapeutic failure to cytarabine plus idarubicin or fludarabine. Cases of primary refractoriness to treatment were associated with a lower number of DNA variants at diagnosis than cases of relapse (median 1.67 and 3.21, respectively, P=0.029). The most frequently affected pathways in patients with primary refractoriness were signaling, transcription and tumor suppression, whereas methylation and splicing pathways were mainly implicated in relapsed patients. New therapeutic targets, either by an approved drug or within clinical trials, were not identified in any of the cases of refractoriness (zero of ten); however, eight potential new targets were found in five relapsed patients (five of 13, P=0.027): one IDH2, three SF3B1, two KRAS, one KIT and one JAK2. Sixty-five percent of all variants detected at diagnosis were not detected at complete response. Specifically, 100% of variants in EZH2, RUNX1, VHL, FLT3, ETV6, U2AF1, PHF6 and SF3B1 disappeared at complete response, indicating their potential use as markers to evaluate minimal residual disease for follow-up of AML. Molecular follow-up using a custom NGS myeloid panel of 32 genes in the post-treatment evaluation of AML can help in the stratification of prognostic risk, the selection of minimal residual disease markers to monitor the response to treatment and guide post-remission strategies targeting AML, and the selection of new drugs for leukemia relapse.

Drug discovery allows the discovery of molecules with pharmacological activity, and it is well-known to be a great time and cost consuming process. Indeed, there are millions of potential druglike ...

Refractoriness to induction therapy and relapse after complete remission are the leading causes of death in patients with acute myeloid leukaemia (AML). This study focussed on the prediction of response to standard induction therapy and outcome of patients with AML using a combined strategy of mutational profiling by next-generation sequencing (NGS, n = 190) and ex vivo PharmaFlow testing (n = 74) for the 10 most widely used drugs for AML induction therapy, in a cohort of adult patients uniformly treated according to Spanish PETHEMA guidelines. We identified an adverse mutational profile (EZH2, KMT2A, U2AF1 and/or TP53 mutations) that carries a greater risk of death [hazard ratio (HR): 3·29, P < 0·0001]. A high correlation was found between the ex vivo PharmaFlow results and clinical induction response (69%). Clinical correlation analysis showed that the pattern of multiresistance revealed by ex vivo PharmaFlow identified patients with a high risk of death (HR: 2·58). Patients with mutation status also ran a high risk (HR 4·19), and the risk was increased further in patients with both adverse profiles (HR 4·82). We have developed a new score based on NGS and ex vivo drug testing for AML patients that improves upon current prognostic risk stratification and allows clinicians to tailor treatments to minimise drug resistance.

Higher Educational Institutions (HEIs) are responsible for creating healthy and sustainable environments for students and teachers through diverse educational paradigms such as gamification. In this sense, the Healthy People 2030 and the Sustainable Development Goals indicated the imperative to provide inclusive and equitable quality education to promote a healthy environment and life. The principal objective was to analyse the impact of gamification on health development in HEIs, highlighting their positive and negative effects. To achieve such an objective, a bibliometric analysis was carried out. The 257 documents showed no significant increasing trend in the last decade (p > 0.05) related to the pandemic. Most of the publications were conferences (45%), and the few published articles were the documents with more citations (p < 0.001). According to their index in Journal Citation Reports, there were significant differences between the citations of articles published in journals (p < 0.001). The analysis of journal co-citations showed that the leading journals (such as Computers in Human Behavior) had a significant part in the clusters formed (p < 0.001), conditioning also the keywords, especially the term “motivation”. These findings were discussed, concluding that the experimental studies focused on the teachers’ adverse effects are yet to come.

The outcome of acute myeloid leukemia patients aged 70 years or older is poor. Defining the best treatment option remains controversial especially when choosing between intensive chemotherapy and hypomethylating agents. We set up a multicentric European database collecting data of 3 700 newly diagnosed acute myeloid leukemia patients ≥70 years. The primary objective was to compare overall survival in patients selected for intensive chemotherapy (n = 1199) or hypomethylating agents (n = 1073). With a median follow-up of 49.5 months, the median overall survival was 10.9 (95% CI: 9.7–11.6) and 9.2 months (95% CI: 8.3–10.2) with chemotherapy and hypomethylating agents, respectively. Complete remission or complete remission with incomplete hematologic recovery was 56.1% and 19.7% with chemotherapy and hypomethylating agents, respectively (P

Intestinal failure (IF) is the inability of the gut to absorb necessary water, macronutrients, micronutrients, and electrolytes sufficient to sustain life and requiring intravenous supplementation or replacement. IF Types 1 and 2 are the initial phase of this condition and usually last for weeks to a few months. Type 3 IF (also known as chronic IF [CIF]) is a chronic and stable condition, usually irreversible, whose main treatment is home parenteral nutrition. CIF is a relatively rare condition, and its prevalence and different causes vary throughout the world. Due to its complexity, CIF requires a multidisciplinary team with experience in this field to achieve successful outcomes. This editorial aims to provide an overview of CIF in adults, emphasizing the challenges faced by clinicians when managing this rare entity, as well as outlining the role of the gastroenterologist.

The aim of the IBDU is to provide comprehensive care for patients with IBD (1,2). During the COVID-19 pandemic, telephone medical consultations and telemedicine training sessions were implemented to ensure patient safety (3). The aim of this study was to determine whether there was a difference in the degree of satisfaction between face-to-face and telephone care, as well as in the annual patient sessions.

Evidence of sexual aggression may be obtained from superabsorbent polymer (SAP) sanitary pads, which are used by forensic laboratories for semen evaluation. Semen can be extracted from their upper layers, which are free of SAPs. However, our previous results showed a need to optimize the protocol for semen analysis by considering its extraction from the lower core, often composed of sodium polyacrylate SAPs. SAPs generate a hydrogel, which traps the cellular components, hindering the possibility of obtaining cells and hence their genetic material. Simple filtration has been tried previously, but further maximization by application of a treatment has never been attempted. In this paper, we compare both chemical and physical shredding treatments for maximizing gel-trapped sperm and male cell DNA recaptures from hygienic superabsorbent substrates in sanitary pads, panty-liners or diapers. Our findings suggest that the lower core should be treated to induce a dewaterisation of the SAP hydrogels in order to maximize the extraction of bodily fluids.

Digital, The aim of this study was to evaluate the impact on muscle strength, aerobic fitness and body composition, of replacing the physical education (PE) class of Colombian adolescents with resistance or aerobic training. 120 tanner stage 3 adolescents attending a state school were randomized to resistance training, aerobic training, or a control group who continued to attend a weekly 2- hour PE class for 16 weeks. The resistance training and aerobic training groups participated in twice weekly supervised after-school exercise sessions of < 1 hour instead of their PE class. Sum of skinfolds, lean body mass (bioelectrical impedance analysis), muscular strength (6 repetition maximum (RM)) bench press, lateral pulldown and leg press) and estimated cardiorespiratory fitness (multistage 20 meter shuttle run) were assessed at pre and post intervention. Complete data were available for n = 40 of the resistance training group, n = 40 of the aerobic training group and n = 30 PE (controls). Resistance training attenuated increases in sum of skinfolds compared with controls (d = 0.27, [0.09–0.36]). We found no significant effect on lean body mass. Resistance training produced a positive effect on muscle strength compared with both controls (d = 0.66 [.49-.86]) and aerobic training (d = 0.55[0.28–0.67]). There was a positive effect of resistance training on cardiorespiratory fitness compared with controls (d = 0.04 [-0.10–0.12]) but not compared with aerobic training (d = 0.24 [0.10–0.36]). Replacing a 2-hour PE class with two 1 hour resistance training sessions attenuated gains in subcutaneous adiposity, and enhanced muscle strength and aerobic fitness development in Colombian youth, based on a median attendance of approximately 1 session a week. Further research to assess whether adequate stimuli for the development of muscular fitness exists within current physical education provision is warranted., Data Availability: The data underlying this study are publicly available at the Dryad repository: https://doi.org/10.5061/dryad.bk3j9kd9q, Funding: FOSCAL received funding for this project in the form of a grant (2014 Colciencias grant ID: 651765741093 number:657), which was awarded to DDC and PAC and used for equipment and other human resources relating to the present study., Ciencias Médicas y de la Salud

In 1842 William Bowman described the microvascular system of the Malpighian body. Electron microscopic studies definitively revealed the spatial structure of its mesangial-capillary-epithelial component. In 1952-54 Trabucco and Marquez challenged the ideas of Bowman, demonstrating the existence of a single glomerular arteriole. Our study supports the finding of a single glomerular arteriole, leading to a definitive interpretation of the Malpighian body structure.Serial histological studies were carried out of the vascular pole in a case of oligomeganephrotic renal hypoplasia and the immunohistochemical study of embryonal glomerular development (15 embryos aged between 7 and 11weeks), with alpha-actin (smooth muscle marker), CD31 and CD34 (endothelial markers) and CD10 (podocyte marker).The study of the glomerular vascular pole in the case of oligomeganephrotic renal hypoplasia supports the existence of a single glomerular arteriole. Our immunohistochemical study confirmed this finding and provided data on the morphogenesis of the mesangial-capillary-epithelial component of the Malpighian body.There exist a single glomerular arteriole. Mesangial and endothelial cells originating from a single glomerular arteriole interact with an epithelial component derived from the nephrogenic vesicle which then generate the lobular glomerular tuft, providing the basis for a definitive interpretation of the structure of the Malpighian body. There is no scientific base to the interpretation of the glomerular microvascular system as having two glomerular arterioles with an intercalated capillary network.

© 2021 The Author(s)., The potential prognostic value of conventional karyotyping in adult T-cell acute lymphoblastic leukemia (T-ALL) remains an open question. We hypothesized that a modified cytogenetic classification, based on the number and type of cytogenetic abnormalities, would allow the identification of high-risk adult T-ALL patients. Complex karyotype defined by the presence of ≥3 cytogenetic alterations identified T-ALL patients with poor prognosis in this study. Karyotypes with ≥3 abnormalities accounted for 16 % (22/139) of all evaluable karyotypes, corresponding to the largest poor prognosis cytogenetic subgroup of T-ALL identified so far. Patients carrying karyotypes with ≥3 cytogenetic alterations showed a significantly inferior response to therapy, and a poor outcome in terms of event-free survival (EFS), overall survival (OS) and cumulative incidence of relapse (CIR), independently of other baseline characteristics and the end-induction minimal residual disease (MRD) level. Additional molecular analyses of patients carrying ≥3 cytogenetic alterations showed a unique molecular profile that could contribute to understand the underlying molecular mechanisms of resistance and to evaluate novel targeted therapies (e.g. IL7R directed) with potential impact on outcome of adult T-ALL patients., This project was supported by the AECC (GC16173697BIGA); ISCIII (PI19/01828) co-funded by ERDF/ESF "A way to make Europe"/ "Investing in your future", CERCA/Generalitat de Catalunya SGR 2017 288 (GRC)/ “La Caixa” P. Barba was supported by the Instituto de Salud Carlos III FIS16/01433 and PERIS 2018-2020 from Generalitat de Catalunya (BDNS357800).

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)

Next-Generation Sequencing has recently been introduced to efficiently and simultaneously detect genetic variations in acute myeloid leukemia. However, its implementation in the clinical routine raises new challenges focused on the diversity of assays and variant reporting criteria. To overcome this challenge, the PETHEMA group established a nationwide network of reference laboratories aimed to deliver molecular results in the clinics. We report the technical cross-validation results for next-generation sequencing panel genes during the standardization process and the clinical validation in 823 samples of 751 patients with newly diagnosed or refractory/relapse acute myeloid leukemia. Two cross-validation rounds were performed in seven nationwide reference laboratories in order to reach a consensus regarding quality metrics criteria and variant reporting. In the pre-standardization cross-validation round, an overall concordance of 60.98% was obtained with a great variability in selected genes and conditions across laboratories. After consensus of relevant genes and optimization of quality parameters the overall concordance rose to 85.57% in the second cross-validation round. We show that a diagnostic network with harmonized next-generation sequencing analysis and reporting in seven experienced laboratories is feasible in the context of a scientific group. This cooperative nationwide strategy provides advanced molecular diagnostic for acute myeloid leukemia patients of the PETHEMA group.

Fibromyalgia (FM) is a chronic syndrome characterized by heterogeneous clinical manifestations, and knowing this variability can help to develop tailored treatments. To understand better the heterogeneity of FM the present crosssectional study analyzed the role of several physical symptoms (pain, fatigue and poor sleep quality) and cognitive-affective variables related to pain (pain catastrophizing, pain vigilance, self-efficacy in pain management, and pain acceptance) in the configuration of clinical profiles. A sample of 161 women with FMfulfilled an interview and several self-report measures to explore physical symptoms, cognitive-affective variables, disability and psychopathology. To establish FM groups a hierarchical cluster analysis was performed. The findings revealed three clusters that differed in the grouping variables, Wilks’ λ = .17, F(14, 304) = 31.50, p < .001, ηp2 = .59.Group 1 (n = 72) was characterized by high physical and psychological affectation, Group 2 (n = 19) by lowphysical affectation and high pain self-efficacy, and Group 3 (n = 70) bymoderate physical affectation and low pain catastrophizing. The external validation of the clusters was confirmed, Wilks’ λ = .72, F(4, 314) = 14.09, p < .001, ηp2 = .15, showing Group 1 the highest levels of FMimpact and psychopathological distress. Considering the distinctive clinical characteristics of each subgroup therapeutic strategies addressed to the specific needs of each group were suggested. Assessing FM profiles may be key for a better understanding and approach of this syndrome., Spanish Government PSI2014-58379-P PID2019-109612GB-I00/AEI/10.13039/501100011033

A massive “infodemic” developed in parallel with the global COVID-19 pandemic and contributed to public misinformation at a time when access to quality information was crucial. This research aimed to analyze the science and health-related hoaxes that were spread during the pandemic with the objectives of (1) identifying the characteristics of the form and content of such false information, and the platforms used to spread them, and (2) formulating a typology that can be used to classify the different types of hoaxes according to their connection with scientific information. The study was conducted by analyzing the content of hoaxes which were debunked by the three main fact-checking organizations in Spain in the three months following WHO’s announcement of the pandemic (N = 533). The results indicated that science and health content played a prominent role in shaping the spread of these hoaxes during the pandemic. The most common hoaxes on science and health involved information on scientific research or health management, used text, were based on deception, used real sources, were international in scope, and were spread through social networks. Based on the analysis, we proposed a system for classifying science and health-related hoaxes, and identified four types according to their connection to scientific knowledge: “hasty” science, decontextualized science, badly interpreted science, and falsehood without a scientific basis. The rampant propagation and widespread availability of disinformation point to the need to foster media and scientific caution and literacy among the public and increase awareness of the importance of timing and substantiation of scientific research. The results can be useful in improving media literacy to face disinformation, and the typology we formulate can help develop future systems for automated detection of health and science-related hoaxes.

Cardiac rehabilitation is supported by the highest level of scientific evidence. However, less than 25% of those eligible to participate in a cardiac rehabilitation program initiate it, and of these, 50% drop out prematurely. A modified Spanish Cardiac Rehabilitation Barriers Scale (CRBS) has been translated, culturally adapted and validated in Colombia, however, the reliability remains to be evaluated. This study aimed to determine the internal consistency and test–retest reliability of the CRBS in a Colombian population. In total, 193 patients (67% men, average age = 65 ± 12 years) completed the scale twice, with an average of eight days between applications. Cronbach’s Alpha and intraclass correlation coefficients (ICC) were calculated. The internal consistency of the Colombian version of the CRBS was acceptable (Cronbach’s alpha = 0.84). The ICC of the CRBS was 0.69 (95% CI 0.61–0.76), 0.78 (95% CI 0.71–0.84) when the CRBS was completed by interview, and 0.47 (95% CI 0.21–0.67) when the CRBS was self-reported. The reliability of the interview version of the CRBS was substantial in the Colombian population, however, the reliability of the self-report version was lower. The use of this scale will allow developing strategies to increase participation and adherence to cardiac rehabilitation programs.

Background Patients with cancer have been shown to have a higher risk of clinical severity and mortality compared to non-cancer patients with COVID-19. Patients with hematologic malignancies typically are known to have higher levels of immunosuppression and may develop more severe respiratory viral infections than patients with solid tumors. Data on COVID-19 in patients with hematologic malignancies are limited. Here we characterize disease severity and mortality and evaluate potential prognostic factors for mortality. Methods In this population-based registry study, we collected de-identified data on clinical characteristics, treatment and outcomes in adult patients with hematologic malignancies and confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection within the Madrid region of Spain. Our case series included all patients admitted to 22 regional health service hospitals and 5 private healthcare centers between February 28 and May 25, 2020. The primary study outcome was all-cause mortality. We assessed the association between mortality and potential prognostic factors using Cox regression analyses adjusted for age, sex, comorbidities, hematologic malignancy and recent active cancer therapy. Results Of 833 patients reported, 697 were included in the analyses. Median age was 72 years (IQR 60–79), 413 (60%) patients were male and 479 (69%) and 218 (31%) had lymphoid and myeloid malignancies, respectively. Clinical severity of COVID-19 was severe/critical in 429 (62%) patients. At data cutoff, 230 (33%) patients had died. Age ≥ 60 years (hazard ratios 3.17–10.1 vs 2 comorbidities (1.41 vs ≤ 2), acute myeloid leukemia (2.22 vs non-Hodgkin lymphoma) and active antineoplastic treatment with monoclonal antibodies (2·02) were associated with increased mortality; conventional chemotherapy showed borderline significance (1.50 vs no active therapy). Conversely, Ph-negative myeloproliferative neoplasms (0.33) and active treatment with hypomethylating agents (0.47) were associated with lower mortality. Overall, 574 (82%) patients received antiviral therapy. Mortality with severe/critical COVID-19 was higher with no therapy vs any antiviral combination therapy (2.20). Conclusions In this series of patients with hematologic malignancies and COVID-19, mortality was associated with higher age, more comorbidities, type of hematological malignancy and type of antineoplastic therapy. Further studies and long-term follow-up are required to validate these criteria for risk stratification.

Complications following hallux valgus (HV) reconstruction will have an expected incidence of between 10% and 55% of cases. The more commonly reported complications include undercorrection/recurrence, overcorrection (hallux varus), transfer metatarsalgia, nonunion, malunion, avascular necrosis, arthritis, hardware removal, nerve injury, and ultimately patient dissatisfaction. The presence of arthritis will be an indication for fusion, whereas osteotomies will be the procedure of choice if the first metatarsophalangeal joint is healthy. Wide experience in primary HV surgery is advised before dealing with complex cases of failed HV surgery.

[Background]: The treatment of acute lymphoblastic leukemia (ALL) in older adults and elderly patients is a challenge, and modern protocols include targeted therapy and immunotherapy in combination with attenuated or minimal chemotherapy. However, frail patients are excluded from these trials, and reports on the outcome of this subgroup of patients are scarce. Our objective was to analyze the outcome of unfit older adults and elderly patients with Philadelphia chromosome-negative ALL included in a prospective trial (ALL-07FRAIL)., [Patients and Methods]: Older adults and elderly patients with Charlson Comorbidity Index (CCI) ≥ 4 were included. Induction therapy consisted of vincristine and dexamethasone, and maintenance therapy with mercaptopurine and methotrexate for 2 years., [Results]: Seventy-two patients with a median age of 67 years (range, 57-89 years) and a median CCI of 5 (range, 4-12) were included. The rates of early withdrawal, early death, resistance, and complete response (CR) were 5%, 10%, 31%, and 54%, respectively. Six patients with CR abandoned the study, 5 died in CR, and 23 relapsed (cumulative relapse incidence 75%). The medians of disease-free and overall survival (OS) were 6.9 months (95% confidence interval [CI], 0.3-13.5 months) and 7.6 months (95% CI, 6.3-8.9 months), respectively. The most frequent toxic events were hematologic (neutropenia 77% and thrombocytopenia 54%, of grade III-IV in all cases). Eastern Cooperative Oncology Group score but not the CCI had significant impact on OS., [Conclusion]: Complete remission with very attenuated chemotherapy can be attained in one-half of older or elderly infirm patients with ALL. These results suggest that some of these patients could benefit from the concomitant or subsequent use of immunotherapy and/or targeted therapy., This study was supported in part by the CERCA Program/Generalitat de Catalunya, Spain and the Josep Carreras Leukemia Research Institute, Badalona, Spain.

Background The effectiveness of the switch to another anti–tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. Methods We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. Results A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8–3; P < 0.0001) and ulcerative colitis vs Crohn’s disease (HR, 1.6; 95% CI, 1.1–2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. Conclusions Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response.

Background Reports of fatal anaphylaxis remain scarce because of the rarity of the condition and the fact that information is limited to a few countries. Objective Our objective was to investigate clinical and demographic characteristics and the causes of fatal anaphylaxis in Spain using two databases of cases of fatal anaphylaxis. Methods We analysed fatal anaphylaxis in a series from the Spanish hospital system and a series from the National Institute of Toxicology and Forensic Sciences (Instituto Nacional de Toxicologia y Ciencias Forenses [INTCF]), which predominantly comprise extrahospital deaths. Deaths from the Spanish hospital system were retrieved from among all deaths occurring during 1998-2011 using codes related to anaphylaxis. Deaths due to anaphylaxis in the INTCF database during the same period were retrieved by 2 allergists, who identified cases in which anaphylaxis was a possible cause of death. A logistic regression model was constructed to predict the characteristics of fatal anaphylaxis in each database. Results The incidence of death by anaphylaxis in Spain using both databases was 0.25 (95% CI, 0.24-0.26) deaths per million person-years. The most frequent causes of death in the hospital system were drugs (46.1%), unknown causes (40.0%), and foods (10.4%); in the INTCF, the most common causes of death were drugs (47.2%), insect stings (30.6%), and foods (11.1%). The logistic regression model showed that fatal anaphylaxis due to unknown causes (OR 15.2, 95% CI 1.8-129.8) was more likely in the hospital database, whereas insect stings (OR 100, 95% CI 10-833.3) and previous atopic comorbidity (OR 15.2, 95% CI 6.3-33.3) were more likely in the INTCF database. Conclusions & clinical relevance The estimated frequency of fatal anaphylaxis in Spain was among the lowest reported. Future studies of fatal anaphylaxis should use databases from different origins in order to show the considerable heterogeneity in this type of death.

The role of NADPH oxidase (Nox)-derived reactive oxygen species in kidney vascular function has extensively been investigated in the harmful context of oxidative stress in diabetes and obesity-associated kidney disease. Since hydrogen peroxide (H2O2) has recently been involved in the non-nitric oxide (NO) non-prostanoid relaxations of intrarenal arteries, the present study was sought to investigate whether NADPH oxidases may be functional sources of vasodilator H2O2 in the kidney and to assess their role in the endothelium-dependent relaxations of human and rat intrarenal arteries. Renal interlobar arteries isolated from the kidney of renal tumor patients who underwent nephrectomy, and from the kidney of Wistar rats, were mounted in microvascular myographs to assess function. Superoxide (O2.-) and H2O2 production was measured by chemiluminescence and Amplex Red fluorescence, and Nox2 and Nox4 enzymes were detected by Western blotting and by double inmunolabeling along with eNOS. Nox2 and Nox4 proteins were expressed in the endothelium of renal arterioles and glomeruli co-localized with eNOS, levels of expression of both enzymes being higher in the cortex than in isolated arteries. Pharmacological inhibition of Nox with apocynin and of CYP 2C epoxygenases with sulfaphenazol, but not of the NO synthase (NOS), reduced renal NADPH-stimulated O2.- and H2O2 production. Under conditions of cyclooxygenase and NOS blockade, acetylcholine induced endothelium-dependent relaxations that were blunted by the non-selective Nox inhibitor apocynin and by the Nox2 or the Nox1/4 inhibitors gp91ds-tat and GKT136901, respectively. Acetylcholine stimulated H2O2 production that was reduced by gp91ds-tat and by GKT136901. These results suggest the specific involvement of Nox4 and Nox2 subunits as physiologically relevant endothelial sources of H2O2 generation that contribute to the endothelium-dependent vasodilatation of renal arteries and therefore have a protective role in kidney vasculature., Graphical abstract fx1

Establishing the cellular or tissue-type origin of human biological traces found at crimes scenes is forensically relevant, as it allows evaluating the crime relevance of such traces and enables reconstructing the sequence of crime events. Messenger RNA and micro RNA markers are useful for forensic tissue identification, but provide challenges for linking RNA-identified cell/tissue types with DNA-identified trace donors, especially in mixed traces. DNA methylation markers overcome this problem, but provide technical challenges due to the DNA treatment required by most analysis methods. Here we introduce a novel type of DNA markers for forensic tissue identification analysed without prior DNA treatment, namely copy number variation (CNV). Using genome-wide CNV screening followed-up by targeted qPCR confirmation, and using qPCR analysis of additional CNV-like candidate DNA markers, in samples of several individuals from all commonly encountered forensically-relevant tissue types, we identified DNA markers specific for blood and semen, respectively. Preliminary forensic validation testing demonstrates that the developed qPCR assays are highly sensitive - delivering positive results down to picogram level of input DNA, specific, and can cope well with degraded DNA, providing suitable prerequisites for forensic applications. Moreover, we exemplified that using the CNV qPCR products as input material for subsequent forensic STR analysis delivered full STR profiles, opening-up new avenues of using the same DNA aliquot for both forensic purposes, tissue and individual identification. Provided additional forensic validation studies, we envision the application of these novel DNA markers for forensic tissue identification in future forensic casework. Such CNV markers are particularly useful for tissue identification in old/cold cases, where aged/old DNA extracts are available that contain no RNA and are not suitable for DNA methylation analysis due to limited DNA quantity and quality.

Objectives To analyse the predictive values of inflammatory back pain (IBP), positive HLA B27 antigen, increased C-reactive protein (CRP), Spondyloarthritis (SpA) features, familial history (FH), magnetic resonance sacroiliac joints (MRI-SIJ) imaging and its weight in early SpA diagnosis. Methods 133 patients with back pain, aged Results The average age was 38.9 years. 47 (35.3%) patients received SpA diagnosis according to the clinical opinion. IBP was highly specific, 0.81 and sensitive, 0.83. HLA B27 was positive in a half of the SpA patients. SPBME ≥2 provided a great specificity, 0.94 and an acceptable sensitivity, 0.79. Erosion was significantly more frequent in SpA patients (72% vs 7%), specificity 0.93. The addition of erosion ≥1 to the WPBME ≥2 noticeably improved specificity, 0.98, although slightly decreased sensitivity, 0.64. Fat metaplasia and backfill were highly specific, but poorly sensitive. Factors forecasting positive diagnosis were IBP, followed by SpA features and increased CRP. Conclusions At the onset, IBP might be a good marker for selecting patients with suspicion of SpA. The addition of erosion to the ASAS criterion might be helpful for early diagnosis, especially in patients with doubtful STIR imaging where BME is present but it is hard to determinate whether the ASAS “highly suggestive” criterion is met.

Aim To assess the likelihood of detecting latent tuberculosis infection [LTBI] by the positive conversion of a serial tuberculin skin test [TST] at 1 year in inflammatory bowel disease [IBD] patients with negative baseline two-step TST. Methods In this multicentre prospective cohort study, we evaluated rate and predictors of conversion of TST at 1 year in patients with negative baseline TST. We also evaluated management of patients who had a positive TST at baseline or a conversion at 1 year. In all patients we assessed TB cases occurring during follow-up. Results Of the 192 IBD patients receiving anti-tumour necrosis factor [TNF] and 220 IBD controls not receiving anti-TNF, 35 [8.5%, 95% CI 5.7-11.3] had positive conversion (median TST induration 13 mm, interquartile range [IQR] 9-16). Ten anti-TNF cohort patients [5.2%, 95% CI 2.5-9.5] versus 25 controls [11.4%, 95% CI 7.5-16.3] had TST conversion [p = 0.029]. In multivariate analysis, conversion was associated with smoking habit (odds ratio [OR] 2.19, 95% CI 1.08-3.97; p = 0.028). Anti-TNF-treated patients had a lower conversion rate [OR 0.41, 95% CI 0.20-0.83; p = 0.013]. The likelihood of conversion correlates with fewer immunosuppressive therapies between baseline TST and TST at 1 year [p = 0.042]. One case of active TB [isoniazid-resistant strain] occurred in a patient with positive baseline TST receiving anti-TNF [0.05 events/100 patient-years]. Conclusions Serial TST at 1 year can detect LTBI in IBD patients receiving anti-TNF therapy with negative baseline TST. Serial TST seems to be advisable to reduce the risk of TB cases associated with inability to detect LTBI in pre-treatment screening.

Background and objective The standardization of treatment of older adults with Philadelphia chromosome negative (Ph-) acute lymphoblastic leukemia (ALL) is challenging, especially in the age range of 55–65 years. This study aimed to compare intensive, pediatric-inspired therapy with non-intensive therapy in this population of patients. Patients and methods The outcomes of 67 patients prospectively included in two consecutive pediatric-inspired intensive protocols (ALL-HR03 and ALL-HR11) from the Spanish PETHEMA Group were compared with those from 44 patients included in a contemporary semi-intensive protocol (ALL-OLD07). Results Baseline patient and ALL characteristics were similar in both groups, except for a younger median age in the intensive group (medians: 58 vs. 62 years). Patients treated intensively had a higher complete remission rate (85% vs. 64%, p = 0.005), a lower cumulative incidence of relapse (39% [95%CI, 25% to 52%] vs. 60% [95%CI, 38% to 77%], p = .003), a similar cumulative incidence of treatment-related mortality (28% [95% CI, 18%, 40%] vs. 21% [95% CI, 10%, 34%]) and superior event-free survival at 2 years (37% [95%CI, 25%–49%) vs. 21% [8%-34%], p = 0.002). On multivariable analysis the type of protocol was the only variable with independent significance for event-free survival (HR [95% CI]: 2 [1.3, 3], p = .002). Conclusions Compared with less intensive chemotherapy, pediatric-inspired intensive chemotherapy significantly improves the outcome of older adults with Ph-negative ALL in the age range of 55–65 years.

Background Capsule endoscopy (CE) is the first-line investigation in cases of suspected Crohn's disease (CD) of the small bowel, but the factors associated with a higher diagnostic yield remain unclear. Objective Our aim is to develop and validate a scoring index to assess the risk of the patients in this setting on the basis of biomarkers. Patients and methods Data on fecal calprotectin, C-reactive protein, and other biomarkers from a population of 124 patients with suspected CD of the small bowel studied by CE and included in a PhD study were used to build a scoring index. This was first used on this population (internal validation process) and after that on a different set of patients from a multicenter study (external validation process). Results An index was designed in which every biomarker is assigned a score. Three risk groups have been established (low, intermediate, and high). In the internal validation analysis (124 individuals), patients had a 10, 46.5, and 81% probability of showing inflammatory lesions in CE in the low-risk, intermediate-risk, and high-risk groups, respectively. In the external validation analysis, including 410 patients from 12 Spanish hospitals, this probability was 15.8, 49.7, and 80.6% for the low-risk, intermediate-risk, and high-risk groups, respectively. Conclusion Results from the internal validation process show that the scoring index is coherent, and results from the external validation process confirm its reliability. This index can be a useful tool for selecting patients before CE studies in cases of suspected CD of the small bowel.

A high proportion of patients with acute myeloid leukemia who achieve minimal residual disease negative status ultimately relapse because a fraction of pathological clones remains undetected by standard methods. We designed and validated a high-throughput sequencing method for minimal residual disease assessment of cell clonotypes with mutations of NPM1, IDH1/2 and/or FLT3-single nucleotide variants. For clinical validation, 106 follow-up samples from 63 patients in complete remission were studied by sequencing, evaluating the level of mutations detected at diagnosis. The predictive value of minimal residual disease status by sequencing, multiparameter flow cytometry, or quantitative polymerase chain reaction analysis was determined by survival analysis. The sequencing method achieved a sensitivity of 10 -4 for single nucleotide variants and 10 -5 for insertions/deletions and could be used in acute myeloid leukemia patients who carry any mutation (86% in our diagnostic data set). Sequencing-determined minimal residual disease positive status was associated with lower disease-free survival (hazard ratio 3.4, P=0.005) and lower overall survival (hazard ratio 4.2, P, This study was supported by the Subdirección General de Investigación Sanitaria (Instituto de Salud Carlos III, Spain) grants PI13/02387 and PI16/01530, and the CRIS against Cancer foundation grant 2014/0120. ML holds a postdoctoral fellowship of the Spanish Ministry of Economy and Competitiveness (FPDI-2013- 16409). PRP holds a postdoctoral fellowship of the Spanish Instituto de Salud Carlos III: Contrato Predoctoral de Formación en Investigación en Salud i-PFIS (IFI 14/00008).

We investigated the frequency, predictors, and evolution of acute lymphoblastic leukemia (ALL) in patients with CNS relapse and introduced a novel method for studying BCR-ABL1 protein variants in cDNA from bone marrow (BM) and cerebrospinal fluid (CSF) blast cells. A total of 128 patients were analyzed in two PETHEMA clinical trials. All achieved complete remission after imatinib treatment. Of these, 30 (23%) experienced a relapse after achieving complete remission, and 13 (10%) had an isolated CNS relapse or combined CNS and BM relapses. We compared the characteristics of patients with and without CNS relapse and further analyzed CSF and BM samples from two of the 13 patients with CNS relapse. In both patients, classical sequencing analysis of the kinase domain of BCR-ABL1 from the cDNA of CSF blasts revealed the pathogenic variant p.L387M. We also performed ultra-deep next-generation sequencing (NGS) in three samples from one of the relapsed patients. We did not find the mutation in the BM sample, but we did find it in CSF blasts with 45% of reads at the time of relapse. These data demonstrate the feasibility of detecting BCR-ABL1 mutations in CSF blasts by NGS and highlight the importance of monitoring clonal evolution over time., This work was supported by the Fundación CRIS and Red Temática de Investigación Cooperativa en Cáncer (RTICC), Instituto de Salud Carlos III (Ref.: RD12/0036/0061 to JML).

Background This work is focused on finding new markers that complement or diagnoses currently used towards improving knowledge histological and statistical aspects that allow us to predict the local stage carcinomas and to identify and understand all the factors related to the progression of this disease. Materials and methods Prostates were obtained from: normal prostates from 20 men, diagnosis of BPH (Benign Prostatic Hyperplasia) from 35 men and prostate cancer from 86 men. We studied the behavior of cytokines that have been implicated in inflammatory processes: TNF-alfa, IL-6, IL-1, EGF and TGF-B. Expression of these cytokines and its receptors was analyzed by immunohistochemistry. Spearman’s test, Kaplan-Meier curves, univariate and multivariate Cox proportional hazard regression analyses were performed. Results Spearman’s analysis showed that there was at least one correlation between TGFB-B, IL-6, gp-130, IL-1B, IL-1R, IL-1RII and clinic pathological feature (preoperative serum PSA, clinical t stage, pathological t stage, positive surgical margins, biochemical progression, survival). Immunostaining score was correlated with some of the clinicopathological feature. In Cox multivariate analysis between the prognostic variables (pathological T stage, Gleason score and lymph node) and immunohistochemical parameters (TGF-B, IL-1a, intensity TGFBRI and intensity TGFBRII) only the expression of IL-1a was retained as independent predictors of biochemical progression after radical prostatectomy. Conclusions Our results suggest a role for prostatic expression of TGF-B, IL-1a, TGFBRI and TGFBRII as prognostic markers for prostate cancer. The rational combination of novel agents directed toward the inactivation of TGF-B, IL-1a, TGFBRI and TGFBRII could disrupt complementary tumor cell proliferation pathways.

Objectives: This study analyzed sleep quality in fibromyalgia (FM) and systemic lupus erythematosus (SLE) and explored its relationship with other clinical and psychological manifestations.Methods:...

Introducción El consumo de ciertos alimentos y los hábitos saludables se relacionan con padecer o prevenir algunas enfermedades crónicas. Estos alimentos suelen estar recogidos en pirámides de alimentación, como las de la Sociedad Española de Nutrición Comunitaria. Una manera de analizar la calidad de la dieta es mediante índices que valoran la frecuencia de consumo de los diferentes alimentos. Objetivo Analizar la calidad de la dieta en la población española mayor de 65 años mediante el índice de alimentación saludable y determinar cómo afectan los factores sociodemográficos al resultado final de la misma. Diseño Se realizó un estudio transversal y descriptivo de la dieta de la población española mayor de 65 años en sus hogares a partir del índice de alimentación saludable, utilizando como información la Encuesta Europea de Salud en España de 2014. Mediante un análisis de regresión lineal múltiple se determinaron los factores socioeconómicos relacionados con la calidad de la dieta. Resultados El 89,6% de la población en estudio necesita cambios en la dieta, y tan solo un 8,2% sigue una dieta saludable. Padecer enfermedades crónicas, tener sobrepeso y realizar actividad física de forma ocasional se asocian con una mejor puntuación en el índice de alimentación saludable. Conclusión La mayor parte de la población de 65 o más años necesita realizar cambios en sus patrones alimentarios. Las personas con riesgos potenciales para la salud son las que cuidan más su alimentación. Estos resultados confirman la necesidad de promover pautas de alimentación saludable en la población sana.

Little research has investigated how traumatic experiences relate to fibromyalgia (FM). We explored the presence of trauma exposure in a sample of Spanish participants with FM and examined the associations between (a) the number and type of traumatic experiences and posttraumatic stress disorder (PTSD) symptoms and (b) the severity of clinical manifestations in FM, testing for possible mediation models. Participants were 173 FM patients and 53 healthy controls aged 24 to 66 years. Traumatic event type (physical trauma, physical and sexual abuse, psychological trauma), PTSD symptoms, pain intensity, sleep disturbance, anxiety, depression, coping style, and daily functioning were evaluated via self-report. Fibromyalgia patients reported a higher percentage of trauma exposure than controls, more traumatic experiences (mainly emotional and physical trauma), and more PTSD symptoms, Hedges' gs/Cohen's ds = 0.42-0.76. Most FM patients reported having experienced their most distressing traumatic experience and PTSD symptoms before FM diagnosis. PTSD symptom severity was associated with more pain, sleep disturbances, anxiety, depression, coping style, and functional impairment, rs = .23-.33, ps = .025-.008. A multiple mediation analysis showed a significant indirect effect of anxiety in the association between PTSD symptoms and daily functioning. In a subset of FM patients, PTSD symptoms were associated with major clinical symptoms. The results suggest future research should explore the effectiveness of trauma-focused therapy compared to standard cognitive behavioral therapy for these patients.

Prostate cancer is one of the most common cancers in the male population. The objective of this investigation was to study the relationship of components of transforming growth factor-B (TGF-β)/phosphoinositide-3-kinases (PI3K)/AKT/mammalian target of rapamycin (mTOR)/nuclear factor kappa B (NF-kB) transduction pathway with clinical-pathological markers. By immunohistochemical methods, we determined the expression of several factors [TGF-β, Transforming Growth Factor B Receptor I (TGFBRI), TGFBRII, PI3K, AKT-Ser, AKT-Thr, mTOR, p-mTOR, inhibitor kB kinase (IKK), pIKK, inhibitor kB (IkB), pIkB, NF-kBp50, and NF-kBp65]. To know their relationship with established classical markers (Preoperative serum prostate specific antigen, pathological tumor stage, clinical tumor stage, Gleason score, perineural invasion, node involvement, positive surgical margins, biochemical progression, and survival) and their importance in the prognosis of biochemical progression, Spearman test, survival analysis, Log-rang test, Kaplan-Meier curves, univariate and multivariate Cox proportional Hazard regression analyses were performed. Spearman analysis showed that there was at least one correlation between TGF-β, TGFBRI, PI3K, pAKT-Thr, p-mTOR, NF-kBp50, and classical markers. Cox multivariate analysis between the prognostic variables (pathological tumor stage, Gleason score, and node involvement) and inmunohistochemical parameters confirmed TGFBR1 and PI3K as a prognostic and independent marker of biochemical progression in prostate cancer. Our results suggest that TGFBR1 and PI3K could be used as useful biomarkers for early diagnosis and prognoses for biochemical recurrence in prostate cancer after radical prostatectomy.

Background and Aims Primary sclerosing cholangitis [PSC] is usually associated with inflammatory bowel disease [IBD]. An increased risk of malignancies, mainly colorectal cancer [CRC] and cholangiocarcinoma [CCA], has been reported in PSC-IBD patients. Our aim was to determine the clinical characteristics and management of PSC in IBD patients, and the factors associated with malignancies. Methods PSC-IBD patients were identified from the Spanish ENEIDA registry of GETECCU. Additional data were collected using the AEG-REDCap electronic data capture tool. Results In total, 277 PSC-IBD patients were included, with an incidence rate of 61 PSC cases per 100 000 IBD patient-years, 69.7% men, 67.5% ulcerative colitis and mean age at PSC diagnosis of 40 ± 16 years. Most patients [85.2%] were treated with ursodeoxycholic acid. Liver transplantation was required in 35 patients [12.6%] after 79 months (interquartile range [IQR] 50–139). It was more common in intra- and extrahepatic PSC compared with small-duct PSC (16.3% vs 3.3%; odds ratio [OR] 5.7: 95% confidence interval [CI] = 1.7–19.3). The incidence rate of CRC since PSC diagnosis was 3.3 cases per 1000 patient-years [95% CI = 1.9–5.6]. Having symptoms of PSC at PSC diagnosis was the only factor related to an increased risk of CRC after IBD diagnosis [hazard ratio= 3.3: 95% CI = 1.1–9.9]. CCA was detected in seven patients [2.5%] with intra- and extrahepatic PSC, with median age of 42 years [IQR 39–53], and presented a lower life expectancy compared with patients without CCA and patients with or without CRC. Conclusions PSC-IBD patients with symptoms of PSC at PSC diagnosis have an increased risk of CRC. CCA was only diagnosed in patients with intra- and extrahepatic PSC and was associated with poor survival.

[Objective and methods]: Pediatric‐inspired regimens have been adopted by several groups as the treatment strategy for adult patients with acute lymphoblastic leukemia (ALL). Whether subsequent modifications of these protocols have led to an improvement in the outcome of patients is uncertain, especially in T‐cell ALL. We analyzed 169 patients with high‐risk T‐cell ALL included in two consecutive trials of the PETHEMA Group (HR‐ALL03 [n = 104] and the more contemporary HR‐ALL11 [n = 65]). [Results]: Patients and disease characteristics were balanced between both groups. Regarding efficacy, we observed a similar complete remission (CR) rate, relapse and disease‐free survival (DFS) between both protocols. Patients included in the HR‐ALL11 trial had better 2‐year overall survival (OS) compared with the HR‐ALL03 (65% [95% CI 51%‐79%] vs 44% [95% CI 34%‐54%], P = 0.026). Regarding toxicity, we observed a better safety profile in the HR‐11 protocol. Irrespective of the protocol, patients with good measurable residual disease (MRD) clearance had a promising outcome without allogeneic hematopoietic stem cell transplantation (allo‐HSCT) in CR1, with 2‐year OS of 67%. [Conclusion]: Patients with T‐cell ALL included in the HR‐11 trial showed better OS than patients in the HR‐03, mostly driven by a reduction of NRM., This work was supported in part by a grant from Generalitat de Catalunya (2017 SGR288 (GRC)); economical support from CERCA Programme/Generalitat de Catalunya and from Fundació Internacional Josep Carreras. The research leading to this invention has received funding from “la Caixa” Foundation. JMR was supported by PI14/01971 from Fondo de Investigaciones Sanitarias. PB was supported by the Instituto de Salud Carlos III FIS16/01433 and PERIS 2018‐2020 from Generalitat de Catalunya (BDNS357800) grants.

Aim: To evaluate outcomes of early dose optimization of golimumab in ulcerative colitis (UC) patients with inadequate response to golimumab induction treatment.Methods: This observational, multicenter, cohort study included patients with moderate-to-severe active UC and with inadequate response to subcutaneous golimumab induction doses, in whom weight-based golimumab maintenance dose (European labeling) of 50mg every 4weeks (q4wk) was optimized before week 14 to 100mg q4wk. At week 14, we assessed clinical response and remission using the partial Mayo score. In the long term we evaluate the cumulative probabilities of golimumab failure-free survival and colectomy-free survival.Results: A total of 209 patients who received golimumab induction doses were eligible. Of these, 151 patients (72.2%) weighing less than 80kg were assigned to a golimumab maintenance dose of 50mg q4wk. Twenty-four patients (15.9% [12.5% overall]), in whom scheduled doses of 50mg q4wk were optimized to 100mg q4wk before week 14, compose the study population. At week 14, 16 patients (66.7%, 95% CI 45.7-87.6) had clinical response, of these 12 were corticosteroid free. Four patients (16.7%) achieved corticosteroid-free remission. After a median follow-up of 12months (IQR 10-22), 13 patients (54.2%) maintained clinical benefit. Thirteen of 16 patients (81.2%) with clinical response at week 14 maintained clinical benefit at last follow-up. All patients avoided colectomy. In none of the patients was golimumab dose de-escalated. There were no adverse events leading to golimumab withdrawal.Conclusion: Early optimization of golimumab dose induces clinical response at week 14 in two thirds of UC patients and leads to long-term clinical benefit in over half of patients.

Background: In APPRECIA trial, Crohn's disease (CD) patients undergoing intestinal resection were randomized to postoperative adalimumab (ADA) or azathioprine (AZA). Aims: To evaluate health-related quality of life (HRQoL) in APPRECIA trial. Methods: HRQoL was evaluated using disease-specific shortened Spanish version of the IBDQ (SIBDQ-9) and generic European Quality of Life-5 Dimensions (EQ-5D) questionnaires, completed at baseline and at weeks 24 and 52. Results: Sixty-one patients (37 ADA and 24 AZA) had evaluable data for HRQoL. Patients treated with ADA or AZA had significant improvement from baseline to weeks 24 and 52 in SIBDQ-9 and EQ-5D (p < 0.001 and p = 0.006 for all comparisons, respectively). There were no differences between treatment arms in mean change in SIBDQ-9 and EQ-5D at weeks 24 and 52 vs baseline. Only patients without endoscopic recurrence had significant improvement in SIBDQ-9 (p < 0.001) and EQ-5D (p < 0.001) at week 52. At week 52, there was a high to moderate negative correlation between CDAI score with SIBDQ-9 score( Pearson's r: -0.768) and with EQ-5D index (r: -0.644). Conclusion: HRQoL improved after intestinal resection in CD, irrespective of the postoperative therapyused (ADA or AZA). Outcomes in HRQoL were associated with prevention of endoscopic recurrence, sinceimprovements in HRQoL were only significant in patients with endoscopic remission at 1 year. (c) 2019 Editrice Gastroenterologica Italiana S. r. l. Published by Elsevier Ltd. All rights reserved.

BACKGROUND Mast cells (MCs) are abundant in the inflammatory infiltrate in eosinophilic oesophagitis (EoE), but decrease with disease remission. However, their phenotype, role in the pathophysiology of the disease, and modulation after effective dietary therapy are still unclear. OBJECTIVE To define the phenotype of oesophageal MCs, their modulation through dietary therapy, and their association with clinical manifestations of EoE. METHODS Oesophageal mucosal samples from 10 adult patients with EoE obtained before and after effective six-food elimination diet (SFED) therapy, as well as from 10 control subjects were analysed. Eosinophil and MC density were quantified. Gene expression of chemoattractants for eosinophils (CCL11, CCL24, and CCL26), MCs (SCF), and their receptors (CCR3 and SCFR, respectively) were assessed by means of qPCR. Gene and protein expression of specific MC proteases (CPA3, CMA, and TPSB2) were evaluated with qPCR and immunofluorescence. Clinical manifestations and atopic background were recorded. RESULTS MC density was significantly increased in EoE compared with controls, decreasing after dietary treatment (18.6 to 1.44 cells/hpf, respectively; P < 0.001). The MCTC subtype predominated in the oesophageal mucosa (90%) in both patients with EoE and controls. Gene expression of MC-related proteases, eotaxins, and SCF were up-regulated in patients with EoE, but significantly decreased after therapy, regardless of atopic background. Epithelial peaks of MCs and eosinophils were significantly associated (ρ = 0.80) in EoE and correlated with the symptom score (ρ = 0.78). Gene expression of MC proteases and eotaxins also correlated with the symptom score (P < 0.05). CONCLUSIONS AND CLINICAL RELEVANCE MC and its proteases seem to play a relevant role in the pathophysiology and symptoms of EoE, which can be reversed after effective dietary treatment.

To evaluate the course of left-sided infective endocarditis (LsIE) in patients with liver cirrhosis (LC) analyzing its influence on mortality and the impact of surgery.Prospective cohort study, conducted from 1984 to 2013 in 26 Spanish hospitals.A total of 3.136 patients with LsIE were enrolled and 308 had LC: 151 Child-Pugh A, 103 B, 34 C and 20 were excluded because of unknown stage. Mortality was significantly higher in the patients with LsIE and LC (42.5% vs. 28.4%; p0.01) and this condition was in general an independent worse factor for outcome (HR 1.51, 95% CI: 1.23-1.85; p0.001). However, patients in stage A had similar mortality to patients without cirrhosis (31.8% vs. 28.4% p = NS) and in this stage heart surgery had a protective effect (28% in operated patients vs. 60% in non-operated when it was indicated). Mortality was significantly higher in stages B (52.4%) and C (52.9%) and the prognosis was better for patients in stage B who underwent surgery immediately (mortality 50%) compared to those where surgery was delayed (58%) or not performed (74%). Only one patient in stage C underwent surgery.Patients with liver cirrhosis and infective endocarditis have a poorer prognosis only in stages B and C. Early surgery must be performed in stages A and although in selected patients in stage B when indicated.