Xenoestrogen concentration in women with endometriosis or leiomyomas: A case-control study.

BACKGROUND: Xenoestrogens are synthetic or naturally occurring chemicals capable of altering the endocrine system of humans and animals owing to their molecular similarity to endogenous hormones. There is limited data regarding their effects on women´s health. Chronic exposure to xenoestrogens can promote the development of estrogen-related diseases. OBJECTIVES: To examine xenoestrogen concentration (TEXB-α) differences between women with leiomyomas or endometriosis and control women, and to study the relationship between the clinical and sociodemographic characteristics of these patients and their xenoestrogen levels. METHODS: Prospective case-control study. We selected 221 women who underwent surgery at Quironsalud Madrid University Hospital between 2017 and 2021. The cases included 117 patients: 74 women who underwent surgery for uterine leiomyomas, 21 with endometriosis, and 22 with both pathologies. The control group comprised 104 healthy women who underwent surgical procedures for other reasons. TEXB-α was determined in the omental fat of all patients. Using a questionnaire and reviewing the patients' medical records, we collected sociodemographic data and other relevant variables. RESULTS: A significant majority of study participants (68.8%) had detectable levels of xenoestrogens. We found no association between TEXB-α levels in omental fat and the presence of myomas or endometriosis. In the case group, women living or working in Madrid Community exhibited, on average, 3.12 Eeq pM/g higher levels of TEXB-α compared to those working in other areas (p = 0.030). Women who referred to the use of estrogen-containing hormonal contraceptives had, on average, 3.02 Eeq pM/g higher levels of TEXB-α than those who had never used them (p = 0.022). CONCLUSIONS: This study found no association between omental xenoestrogen levels and leiomyomas or endometriosis. However, their presence in most participants and their association with highly polluted areas emphasizes the importance of limiting environmental exposure to these substances. We also identified an association between hormonal contraceptive use and xenoestrogen concentration.

Hypofractionated whole breast IMRT with HDR brachytherapy boost in early-stage breast cancer: Long-term results from a single-center.

INTRODUCTION/OBJECTIVES: The addition of a boost to the lumpectomy bed after whole-breast (WB) radiotherapy plays a key role in the treatment of patients with breast cancer (BC). The clinical benefits of a boost with high-dose-rate brachytherapy (HDR-BT) after conventional fractionation is supported by a large body of evidence. However, few studies have described its outcomes after a hypofractionated scheme. MATERIALS AND METHODS: We included all patients treated with adjuvant WB-IMRT in 15 sessions followed by a single-session HDR-BT boost with local anesthesia on an outpatient basis. RESULTS: Between 2009 and 2017, 638 patients with early-stage BC were treated according to the aforementioned protocol after breast-conserving surgery. Median follow-up was 6 years (4-11). Despite the low incidence of side effects and their slightness, we did identify an impact of breast volume on the risk of acute radiodermatitis, fibrosis, pain and edema. However, we did not identify any relationship between the volume in cubic centimeters of the BT-implant with acute or long-term side effects. 2.2% patients had an actual local relapse, 2.4% a 2nd primary in the same breast and 2.39% were diagnosed with contralateral BC. Event-free survival at 11 years was 85.5% with an overall survival of 95.7%. CONCLUSION: Adjuvant hypofractionated whole-breast IMRT followed by a single dose HDR-BT boost has a low incidence of acute and chronic toxicity and excellent oncological outcomes. However, it may be worthwhile to intensify self-care protocols and surveillance in women with large breasts who may be at increased risk of side effects.

Jorge clinical study: 10-year outcomes of risk-adapted radiotherapy defined by multiparametric MRI for prostate cancer.

PURPOSE: To analyze the 10-year biochemical relapse-free survival (BRFS), locoregional relapse-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS) in patients diagnosed with localized prostate adenocarcinoma treated with radiotherapy (RT) ± androgen deprivation therapy (ADT), according to the risk groups based on multiparametric magnetic resonance imaging (mpMRI) instead of digital rectal exam (DRE). METHODS: We retrospectively evaluated 140 consecutive patients diagnosed with localized prostate adenocarcinoma, stratified into different risk groups-low (LR), intermediate (IR), and high (HR) by mpMRI results. RESULTS: After a median follow-up of 104 months, in LR group (n = 15), 10-year BRFS was 86.7%, 10-year LRFS was 86.7%, 10-year MFS was 93.3%, and 10-year OS was 100%. In IR group (n = 80), 10-year BRFS was 80.5%, 10-year LRFS was 86.1%, 10-year MFS was 92.6%, and 10-year OS was 76%. In HR group (n = 45), 10-year BRFS was 72.8%, 10-year LRFS was 78.7%, 10-year MFS was 82.1%, and 10-year OS was 77% (2 deaths from prostate cancer). According to mpMRI results, 36 (25.7%) patients change the risk group and 125 (89.28%) patients change the TNM stage. There was a trend for higher metastatic relapse in patients who switched from IR to HR (due to mpMRI) versus the patients who remained in the IR (20%, vs. 1.81% p = 0.059). Multivariate analysis showed that locoregional relapse was strongly associated with distant relapse (OR = 9.28; 95%CI: 2.60-33.31). There were no cases of acute grade 3 toxicity. Late grade 3 genitourinary, gastrointestinal, and sexual toxicity were 2.8%, 0.7%, and 1.2%, respectively. CONCLUSION: This is the first study with a 10-year median follow-up of patients diagnosed with localized prostate cancer treated with radiotherapy according to the risk groups established by mpMRI. Our findings show that mpMRI is a key tool to diagnose and establish risk groups in these patients, to optimize their treatment.

MYH10 activation rescues contractile defects in arrhythmogenic cardiomyopathy (ACM).

The most prevalent genetic form of inherited arrhythmogenic cardiomyopathy (ACM) is caused by mutations in desmosomal plakophilin-2 (PKP2). By studying pathogenic deletion mutations in the desmosomal protein PKP2, here we identify a general mechanism by which PKP2 delocalization restricts actomyosin network organization and cardiac sarcomeric contraction in this untreatable disease. Computational modeling of PKP2 variants reveals that the carboxy-terminal (CT) domain is required for N-terminal domain stabilization, which determines PKP2 cortical localization and function. In mutant PKP2 cells the expression of the interacting protein MYH10 rescues actomyosin disorganization. Conversely, dominant-negative MYH10 mutant expression mimics the pathogenic CT-deletion PKP2 mutant causing actin network abnormalities and right ventricle systolic dysfunction. A chemical activator of non-muscle myosins, 4-hydroxyacetophenone (4-HAP), also restores normal contractility. Our findings demonstrate that activation of MYH10 corrects the deleterious effect of PKP2 mutant over systolic cardiac contraction, with potential implications for ACM therapy.

Beta-3 adrenergic receptor overexpression reverses aortic stenosis-induced heart failure and restores balanced mitochondrial dynamics.

Aortic stenosis (AS) is associated with left ventricular (LV) hypertrophy and heart failure (HF). There is a lack of therapies able to prevent/revert AS-induced HF. Beta3 adrenergic receptor (ß3AR) signaling is beneficial in several forms of HF. Here, we studied the potential beneficial effect of ß3AR overexpression on AS-induced HF. Selective ß3AR stimulation had a positive inotropic effect. Transgenic mice constitutively overexpressing human ß3AR in the heart (c-hß3tg) were protected from the development of HF in response to induced AS, and against cardiomyocyte mitochondrial dysfunction (fragmented mitochondria with remodeled cristae and metabolic reprogramming featuring altered substrate use). Similar beneficial effects were observed in wild-type mice inoculated with adeno-associated virus (AAV9) inducing cardiac-specific overexpression of human ß3AR before AS induction. Moreover, AAV9-hß3AR injection into wild-type mice at late disease stages, when cardiac hypertrophy and metabolic reprogramming are already advanced, reversed the HF phenotype and restored balanced mitochondrial dynamics, demonstrating the potential of gene-therapy-mediated ß3AR overexpression in AS. Mice with cardiac specific ablation of Yme1l (cYKO), characterized by fragmented mitochondria, showed an increased mortality upon AS challenge. AAV9-hß3AR injection in these mice before AS induction reverted the fragmented mitochondria phenotype and rescued them from death. In conclusion, our results step out that ß3AR overexpression might have translational potential as a therapeutic strategy in AS-induced HF.

Dolor, calidad de vida y salud mental en pacientes con gonalgia por gonartrosis: estudio de casos y controles / Pain, quality of life and mental health in patients with gonalgia due to gonarthrosis: Cases and controls study

Objetivo: Evaluar el dolor, la calidad de vida y el estado psicológico en pacientes con gonalgia por gonartrosis. Material y métodos: Estudio epidemiológico, multicéntrico, de casos y controles. Se incluyeron 1.152 pacientes (576 con artrosis y 576 sin artrosis) apareados por edad y sexo, procedentes de 63 centros de salud de España. Se les administró la escala visual analógica de dolor de Huskisson y los cuestionarios EuroQol y Goldberg. Se realizó un análisis descriptivo y comparativo de los datos en ambos grupos. Se estudiaron los factores que influían en la CV y salud mental de los pacientes artrósicos con modelos de regresión logística. Resultados: Se incluyeron 576 pacientes casos y 576 controles. El 70,3% eran mujeres en ambos grupos. La puntuación media en la escala visual analógica de los artrósicos fue 65,2±4,9mm correspondiente a una intensidad moderada. El cuestionario EuroQol indicó peor estado de salud (p<0,05) en los pacientes con artrosis en todas sus dimensiones. El cuestionario Goldberg mostró la presencia de psicopatología en el 36,5% (n=209) de los casos, frente a un 14,0% (n=80) en los controles (p<0,001). El dolor fue la variable que afectó a la CV en todas las dimensiones (p<0,001). Conclusiones: Los pacientes con artrosis manifiestan dolor moderado, limitación de la movilidad, del cuidado personal y de las actividades cotidianas que repercute negativamente en su CV y psicológicamente se encuentran más afectados. Es prioritario desarrollar estrategias de autocuidado y tratamiento en estos pacientes para mejorar globalmente su CV (AU)

Objective: To evaluate pain, quality of life and psychological state in patients with gonalgia due to gonarthrosis. Material and methods: Epidemiological, multicenter, case–control study. 1.152 patients were included (576 with arthrosis and 576 without arthrosis) matched by age and sex, from 63 health centers in Spain. The Huskisson Pain Scale (VAS), the EuroQol and Goldberg questionnaires were administered. A descriptive and comparative analysis of the data was carried out in both groups. Factors influencing the quality of life and mental health of arthritic patientes were studied with logistic regression models. Results: 576 case patients and 576 controls were included. 70.3% were women in both groups. The mean score in the VAS score of the arthritic patients was 65±4.9mm corresponding to a moderate intensity. The EQ-5D questionnaire indicated a worse state of health (P<.05) in patients with osteoarthritis in each of its dimensions. In the GHQ-12 questionnaire, the presence of psychopathology was detected in 36.5% (n=209) of patients with osteoarthritis compared to 14.0% (n=80) in controls (P<.001). Pain was the variable that affected quality of life in all dimensions (P<.001). Conclusions: Patients with arthrosis manifest moderate pain due to this disease. They present a limitation of mobility, personal care and daily activities that negatively affects their quality of life and psychologically they are more affected. It is a priority to develop self-care and treatment strategies in this group of subjects to globally improve their quality of life (AU)

[Pain, quality of life and mental health in patients with gonalgia due to gonarthrosis: Cases and controls study]. / Dolor, calidad de vida y salud mental en pacientes con gonalgia por gonartrosis: estudio de casos y controles.

OBJECTIVE: To evaluate pain, quality of life and psychological state in patients with gonalgia due to gonarthrosis. MATERIAL AND METHODS: Epidemiological, multicenter, case-control study. 1.152 patients were included (576 with arthrosis and 576 without arthrosis) matched by age and sex, from 63 health centers in Spain. The Huskisson Pain Scale (VAS), the EuroQol and Goldberg questionnaires were administered. A descriptive and comparative analysis of the data was carried out in both groups. Factors influencing the quality of life and mental health of arthritic patientes were studied with logistic regression models. RESULTS: 576 case patients and 576 controls were included. 70.3% were women in both groups. The mean score in the VAS score of the arthritic patients was 65±4.9mm corresponding to a moderate intensity. The EQ-5D questionnaire indicated a worse state of health (P<.05) in patients with osteoarthritis in each of its dimensions. In the GHQ-12 questionnaire, the presence of psychopathology was detected in 36.5% (n=209) of patients with osteoarthritis compared to 14.0% (n=80) in controls (P<.001). Pain was the variable that affected quality of life in all dimensions (P<.001). CONCLUSIONS: Patients with arthrosis manifest moderate pain due to this disease. They present a limitation of mobility, personal care and daily activities that negatively affects their quality of life and psychologically they are more affected. It is a priority to develop self-care and treatment strategies in this group of subjects to globally improve their quality of life.

Sars-Cov-2 Infection in Patients on Long-Term Treatment with Macrolides in Spain: A National Cross-Sectional Study.

The aim of this study was to know the prevalence and severity of COVID-19 in patients treated with long-term macrolides and to describe the factors associated with worse outcomes. A cross-sectional study was conducted in Primary Care setting. Patients with macrolides dispensed continuously from 1 October 2019 to 31 March 2020, were considered. Main outcome: diagnosis of coronavirus disease-19 (COVID-19). Secondary outcomes: symptoms, severity, characteristics of patients, comorbidities, concomitant treatments. A total of 3057 patients met the inclusion criteria. Median age: 73 (64-81) years; 55% were men; 62% smokers/ex-smokers; 56% obese/overweight. Overall, 95% of patients had chronic respiratory diseases and four comorbidities as a median. Prevalence of COVID-19: 4.8%. This was in accordance with official data during the first wave of the pandemic. The most common symptoms were respiratory: shortness of breath, cough, and pneumonia. Additionally, 53% percent of patients had mild/moderate symptoms, 28% required hospital admission, and 19% died with COVID-19. The percentage of patients hospitalized and deaths were 2.6 and 5.8 times higher, respectively, in the COVID-19 group (p < 0.001). There was no evidence of a beneficial effect of long-term courses of macrolides in preventing SARS-CoV-2 infection or the progression to worse outcomes in old patients with underlying chronic respiratory diseases and a high burden of comorbidity.

Sustained Elevated Blood Pressure Accelerates Atherosclerosis Development in a Preclinical Model of Disease.

The continuous relationship between blood pressure (BP) and cardiovascular events makes the distinction between elevated BP and hypertension based on arbitrary cut-off values for BP. Even mild BP elevations manifesting as high-normal BP have been associated with cardiovascular risk. We hypothesize that persistent elevated BP increases atherosclerotic plaque development. To evaluate this causal link, we developed a new mouse model of elevated BP based on adeno-associated virus (AAV) gene transfer. We constructed AAV vectors to support transfer of the hRenin and hAngiotensinogen genes. A single injection of AAV-Ren/Ang (1011 total viral particles) induced sustained systolic BP increase (130 ± 20 mmHg, vs. 110 ± 15 mmHg in controls; p = 0.05). In ApoE-/- mice, AAV-induced mild BP elevation caused larger atherosclerotic lesions evaluated by histology (10-fold increase vs. normotensive controls). In this preclinical model, atheroma plaques development was attenuated by BP control with a calcium channel blocker, indicating that a small increase in BP within a physiological range has a substantial impact on plaque development in a preclinical model of atherosclerosis. These data support that non-optimal BP represents a risk for atherosclerosis development. Earlier intervention in elevated BP may prevent or delay morbidity and mortality associated with atherosclerosis.

Breast cancer radiotherapy: What physicians need to know in the era of the precision medicine.

Breast cancer is the most common cancer in women worldwide and encompasses a broad spectrum of diseases in one with significant epidemiological, clinical, and biological heterogeneity, which determines a different natural history and prognostic profile. Although classical tumour staging (TNM) still provides valuable information, the current reality is that the clinicians must consider other biological and molecular factors that directly influence treatment decision-making. The management of breast cancer has changed radically in the last 15 years due to significant advances in our understanding of these tumours. This knowledge has brought with it a major impact regarding surgical and systemic management and has been practice-changing, but it has also created significant uncertainties regarding how best integrate the radiotherapy treatment into the therapeutic scheme. In parallel, radiotherapy itself has also experienced major advances, new radiobiological concepts have emerged, and genomic data and other patient-specific factors must now be integrated into individualised treatment approaches. In this context, "precision medicine" seeks to provide an answer to these open questions and uncertainties. The aim of the present review is to clarify the meaning of this term and to critically evaluate its role and impact on contemporary breast cancer radiotherapy.

SARS-CoV-2 protein Nsp1 alters actomyosin cytoskeleton and phenocopies arrhythmogenic cardiomyopathy-related PKP2 mutant

Mutations in desmosomal Plakophilin-2 (PKP2) are the most prevalent drivers of arrhythmogenic cardiomyopathy (ACM) and a common cause of sudden cardiac death in young athletes. However, partner proteins that elucidate PKP2 cellular mechanism to understand cardiac dysfunction in ACM are mostly unknown. Here we identify the actin-based motor proteins Myh9 and Myh10 as key PKP2 interactors, and demonstrate that the expression of the ACM-related PKP2 mutant R735X alters actin fiber organization and cell mechanical stiffness. We also show that SARS-CoV-2 Nsp1 protein acts similarly to this known pathogenic R735X mutant, altering the actomyosin component distribution on cardiac cells. Our data reveal that the viral Nsp1 hijacks PKP2 into the cytoplasm and mimics the effect of delocalized R735X mutant. These results demonstrate that cytoplasmic PKP2, wildtype or mutant, induces the collapse of the actomyosin network, since shRNA-PKP2 knockdown maintains the cell structure, validating a critical role of PKP2 localization in the regulation of actomyosin architecture. The fact that Nsp1 and PKP2 mutant R735X share similar phenotypes also suggests that direct SARS-CoV-2 heart infection could induce a transient ACM-like disease in COVID-19 patients, which may contribute to right ventricle dysfunction, observed in patients with poor survival prognosis. HighlightsThe specific cardiac isoform Plakophilin-2a (PKP2) interacts with Myh9 and Myh10. PKP2 delocalization alters actomyosin cytoskeleton component organization. SARS-CoV-2 Nsp1 protein hijacks PKP2 from the desmosome into the soluble fraction where it is downregulated. Viral Nsp1 collapses the actomyosin cytoskeleton and phenocopies the arrhythmogenic cardiomyopathy-related mutant R735X.

The pharmaceutical solvent N-methyl-2-pyrollidone (NMP) attenuates inflammation through Krüppel-like factor 2 activation to reduce atherogenesis.

N-methyl-2-pyrrolidone (NMP) is a versatile water-miscible polar aprotic solvent. It is used as a drug solubilizer and penetration enhancer in human and animal, yet its bioactivity properties remain elusive. Here, we report that NMP is a bioactive anti-inflammatory compound well tolerated in vivo, that shows efficacy in reducing disease in a mouse model of atherosclerosis. Mechanistically, NMP increases the expression of the transcription factor Kruppel-like factor 2 (KLF2). Monocytes and endothelial cells treated with NMP express increased levels of KLF2, produce less pro-inflammatory cytokines and adhesion molecules. We found that NMP attenuates monocyte adhesion to endothelial cells inflamed with tumor necrosis factor alpha (TNF-α) by reducing expression of adhesion molecules. We further show using KLF2 shRNA that the inhibitory effect of NMP on endothelial inflammation and subsequent monocyte adhesion is KLF2 dependent. Enhancing KLF2 expression and activity improves endothelial function, controls multiple genes critical for inflammation, and prevents atherosclerosis. Our findings demonstrate a consistent effect of NMP upon KLF2 activation and inflammation, biological processes central to atherogenesis. Our data suggest that inclusion of bioactive solvent NMP in pharmaceutical compositions to treat inflammatory disorders might be beneficial and safe, in particular to treat diseases of the vascular system, such as atherosclerosis.

High-dose neoadjuvant chemoradiotherapy versus chemotherapy alone followed by surgery in potentially-resectable stage IIIA-N2 NSCLC. A multi-institutional retrospective study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society).

BACKGROUND: The optimal induction treatment in potentially-resectable stage IIIA-N2 NSCLC remains undefined. AIM: To compare neoadjuvant high-dose chemoradiotherapy (CRT) to neoadjuvant chemotherapy (CHT) in patients with resectable, stage IIIA-N2 non-small-cell lung cancer (NSCLC). METHODS: Retrospective, multicentre study of 99 patients diagnosed with stage cT1-T3N2M0 NSCLC who underwent neoadjuvant treatment (high-dose CRT or CHT) followed by surgery between January 2005 and December 2014. RESULTS: 47 patients (47.5%) underwent CRT and 52 (52.5%) CHT, with a median follow-up of 41 months. Surgery consisted of lobectomy (87.2% and 82.7%, in the CRT and CHT groups, respectively) or pneumonectomy (12.8% vs. 17.3%). Nodal downstaging (to N1/N0) and Pathologic complete response (pCR; pT0pN0) rates were significantly higher in the CRT group (89.4% vs. 57.7% and 46.8% vs. 7.7%, respectively; p < 0.001)). Locoregional recurrence was significantly lower in the CRT group (8.5% vs. 13.5%; p = 0.047) but distant recurrence rates were similar in the two groups. Median PFS was 45 months (CHT) vs. "not reached" (CRT). Median OS was similar: 61 vs. 56 months (p = 0.803). No differences in grade ≥3 toxicity were observed. On the Cox regression analysis, advanced pT stage was associated with worse OS and PFS (p < 0.001) and persistent N2 disease (p = 0.002) was associated with worse PFS. CONCLUSIONS: Compared to neoadjuvant chemotherapy alone, a higher proportion of patients treated with preoperative CRT achieved nodal downstaging and pCR with better locoregional control. However, there were no differences in survival. More studies are needed to know the optimal treatment of these patients.

Impact of 68Ga-PSMA PET/CT in the treatment of prostate cancer: Initial experience in Spain.

AIM: To evaluate whether positron-emission tomography/computed tomography with 68Ga-PSMA (68Ga-PSMA PET/CT) influences the therapeutic management of patients with primary or recurrent prostate cancer (PCa). BACKGROUND: Although 68Ga-PSMA PET/CT is one of the best options for staging or restaging patients with PCa, its availability is still very limited in Spain. The present study reports the results of the first group of patients in Spain who underwent 68Ga-PSMA PET/CT imaging. MATERIALS AND METHODS: All patients (n = 27) with a histological diagnosis of PCa who underwent 68Ga-PSMA PET/CT prior to the definitive treatment decision at the only centre with this technology in Spain during 2017-2018 were included. Two nuclear medicine physicians and a radiologist reviewed the imaging studies. The clinical impact was assessed from a theoretical perspective, based on the treatment that would have been applied if no data from the 68Ga-PSMA PET/CT were available. RESULTS: Most patients (n = 26; 96%) had persistent disease or biochemical recurrence after radical prostatectomy, radiotherapy, or combined treatment. One patient underwent 68Ga-PSMA PET/CT imaging to stage high-risk PCa. Overall, 68Ga-PSMA PET/CT was positive in 19 patients (70.4%). In 68.75% of these patients, none of the other imaging tests-MRI, CT, or bone scans-performed prior to the 68Ga-PSMA PET/CT were able to detect the presence of cancerous lesions. Overall, the findings of the 68Ga-PSMA PET/CT led to a modification of the therapeutic approach in 62.96% of the patients in the study. CONCLUSIONS: 68Ga-PSMA PET/CT alters the therapeutic approach in a substantial proportion of patients with PCa.

The clinical benefit of instituting a prospective clinical community-acquired respiratory virus surveillance program in allogeneic hematopoietic stem cell transplantation.

BACKGROUND: There is a lack of studies comparing clinical outcomes among retrospective versus prospective cohorts of allogeneic stem cell transplant (allo-HCT) recipients with community acquired respiratory virus (CARV) infections. METHODS: We compare outcomes in two consecutive cohorts of allo-HCT recipients with CARV infections. The retrospective cohort included 63 allo-HCT recipients with 108 CARV infections from January 2013 to April 2016 who were screened and managed following standard clinical practice based on influenza and respiratory syncytial virus rapid antigen detection methods. The prospective cohort was comprised of 144 consecutive recipients with 297 CARV episodes included in a prospective interventional clinical surveillance program (ProClinCarvSur-P) based on syndromic multiplex PCR as first-line test from May 2016 to December 2018 at a single transplant center. RESULTS: CARV infections in the retrospective cohort showed more severe clinical features at the time of diagnosis compared to the prospective cohort (fever 83% vs. 57%, hospital admission 69% vs. 28% and lower respiratory tract 58% vs. 31%, respectively, p ≤ 0.002 for all comparisons). Antiviral therapy was more commonly prescribed in the prospective cohort (69 vs. 43 treated CARV episodes), particularly at the upper respiratory tract disease stage (34 vs. 12 treated CARV episodes). Three-month all-cause mortality was significantly higher in the retrospective cohort (n = 23, 37% vs. n = 10, 7%, p < 0.0001). Multivariate logistic regression analysis showed that recipients included in ProClinCarvSur-P had lower mortality rate [odds ratio 0.31, 95% confidence interval 0.12-0.7, p = 0.01]. CONCLUSION: This study report on outcome differences when reporting retrospective vs. prospective CARV infections after allo-HCT. Recipients included in a ProClinCarvSur-P had lower mortality.

Antimicrobial Stewardship Programs Are Required in a Department of Surgery: "How" Is the Question A Quasi-Experimental Study: Results after Three Years.

Objective: Our aim was to describe our antimicrobial stewardship program and the methodology based on the results in a surgical department. Methods: Our study was a quasi-experimental study conducted from January 1, 2009, through September 30, 2017. The site was the General and Digestive Surgery Department in a public primary referral center, the University Hospital of Getafe (Madrid, Spain). We implemented the antimicrobial stewardship program following a prospective audit and feedback model, with a surgeon incorporated into the manaagement group. We studied the deaths and 30-day re-admission rates, length of stay, prevalence of gram-negative bacilli, meropenem resistance, and days of treatment with meropenem. Results: After three years of the program, we recorded a significant decrease in Pseudomonas aeruginosa prevalence, a significant increase in Klebsiella pneumoniae prevalence, a decrease in meropenem resistance, and a reduction in meropenem days of treatment. Conclusions: Antimicrobial stewardship programs have a desirable effect on patients. In our experience, the program team should be led by a staff from the particular department. When human resources are limited, the sustainability, efficiency, and effectiveness of interventions are feasible only with adequate computer support. Finally, but no less important, the necessary feedback between the prescribers and the team must be based on an ad hoc method such as that provided by statistical control charts, a median chart in our study.

Prehospital triage for mass casualty incidents using the META method for early surgical assessment: retrospective validation of a hospital trauma registry.

BACKGROUND: In mass casualty incidents (MCI), death usually occurs within the first few hours and thus early transfer to a trauma centre can be crucial in selected cases. However, most triage systems designed to prioritize the transfer to hospital of these patients do not assess the need for surgery, in part due to inconclusive evidence regarding the value of such an assessment. Therefore, the aim of the present study was to evaluate the capacity of a new triage system-the Prehospital Advanced Triage Method (META)-to identify victims who could benefit from urgent surgical assessment in case of MCI. METHODS: Retrospective, descriptive, observational study of a multipurpose cohort of patients included in the severe trauma registry of the Gregorio Marañón University General Hospital (Spain) between June 1993 and December 2011. All data were prospectively evaluated. All patients were evaluated with the META system to determine whether they met the criteria for urgent transfer. The META defines patients in need of urgent surgical assessment: (a) All penetrating injuries to head, neck, torso and extremities proximal to elbow or knee, (b) Open pelvic fracture, (c) Closed pelvic fracture with mechanical or haemodynamic instability and (d) Blunt torso trauma with haemodynamic instability. Patients who fulfilled these criteria were designated as "Urgent Evacuation for Surgical Assessment" (UESA) cases; all other cases were designated as non-UESA. The following variables were assessed: patient status at the scene; severity scales [RTS, Shock index, MGAP (Mechanism, Glasgow coma scale, Age, pressure), GCS]; need for surgery and/or interventional procedure to control bleeding (UESA); and mortality. The two groups (UESA vs. non-UESA) were then compared. RESULTS: A total of 1882 cases from the database were included in the study. Mean age was 39.2 years and most (77%) patients were male. UESA patients presented significantly worse on-scene hemodynamic parameters (systolic blood pressure and heart rate) and greater injury severity (RTS, shock index, and MGAP scales). No differences were observed for respiratory rate, need for orotracheal intubation, or GCS scores. The anatomical injuries of patients in the UESA group were less severe but these patients had a greater need for urgent surgery and higher mortality rates. CONCLUSION: These findings suggest that the META triage classification system could be beneficial to help identify patients with severe trauma and/or in need of urgent surgical assessment at the scene of injury in case of MCI. These findings demonstrate that, in this cohort, the META fulfils the purpose for which it was designed.

Antibody responses to influenza vaccine in patients on biological therapy: Results of RIER cohort study / Respuesta a la vacuna contra la gripe en pacientes que reciben tratamientos biológicos: resultados del estudio de cohortes RIER

Background and objectives: Influenza vaccine is recommended for patients with autoimmune inflammatory rheumatic diseases who receive biological therapy. To evaluate if biological therapy impairs immunization after seasonal influenza vaccine. Material and methods: Patients with inflammatory arthopathies, psoriasis, inflammatory bowel disease or connective tissue diseases who were receiving or were going to initiate biological therapy were included and vaccinated during 2014-2015 influenza season. ELISA was used to measure influenza antigen A and B antibodies, before and after vaccination. Demographic parameters, diagnosis and kind of treatment were recorded and their influence on the final serological status against influenza was studied. Results: 253 subjects were analyzed. After vaccination, 77% of participants presented detectable antibodies against antigen A and 50.6% of them had detectable antibodies against antigen B. Final seropositivity rate against antigen B antibodies increased from baseline (50.6% vs 43.5%, p<0.001). Anti-TNF drugs were associated with better response and rituximab with the worst (79.2% vs 55.0% for final seropositivity against antigen A, p=0.020). Vaccine response in the rituximab group tended to improve when the interval between the drug administration and the vaccination was at least 12 weeks (seropositivity rate 80.0% in those with the longer interval vs 25.0% in the other group, p=0.054). Conclusions: Among the patients on biological therapy vaccinated against influenza, anti-TNF therapy was identified as a predictive factor of final seropositivity. Rituximab presented a lower rate of final seropositivity, which could be increased with an accurate administration schedule

Antecedentes y objetivos: La vacunación antigripal está recomendada en pacientes con enfermedades autoinmunes sistémicas que reciben tratamientos biológicos. Evaluar si la terapia biológica puede perjudicar la inmunización después de la administración de la vacuna contra la gripe estacional. Material y métodos: Los pacientes con artropatías inflamatorias, psoriasis, enfermedad inflamatoria intestinal o enfermedades del tejido conectivo, que estaban en tratamiento o que iban a iniciar tratamiento con terapia biológica, fueron incluidos en el estudio y vacunados durante la temporada de influenza 2014-2015. Se utilizó ELISA para medir los anticuerpos contra los antígenosA y B de la gripe, antes y después de la vacunación. Se registraron los datos demográficos, diagnósticos y el tipo de tratamiento y se estudió su influencia sobre el estado serológico final contra la influenza. Resultados: Se analizaron 253 sujetos. Después de la vacunación, el 77% de los participantes presentaron anticuerpos detectables contra el antígeno A y el 50,6% de ellos tenían anticuerpos detectables contra el antígeno B. La tasa de seropositividad final de anticuerpos contra el antígeno B aumentó desde los valores basales (50,6% frente a 43,5%, p<0,001). Los fármacos anti-TNF se asociaron con la mejor respuesta y rituximab con la peor (79,2% vs. 55,0% para la seropositividad final contra el antígeno A, p=0,020). La respuesta a la vacuna en el grupo de rituximab tuvo tendencia a mejorar cuando el intervalo entre la administración del fármaco y la vacunación fue por lo menos de 12 semanas (tasa de seropositividad del 80,0% en aquellos con el intervalo más largo frente al 25% en el otro grupo, p=0.054). Conclusiones: Entre los pacientes en terapia biológica vacunados contra la influenza, la terapia anti-TNF se identificó como un factor predictivo de la seropositividad final. Rituximab presentó una tasa más baja de seropositividad final, que podría aumentarse con un programa de administración preciso

Correlation between apparent diffusion coefficient values in breast magnetic resonance imaging and prognostic factors of breast invasive ductal carcinoma.

BACKGROUND: We wanted to examine whether the apparent diffusion coefficient values obtained by diffusion-weighted imaging techniques could indicate an early prognostic assessment for patients with Invasive Ductal Carcinoma and, therefore, influence the treatment decision making. OBJECTIVE: The main objective was to evaluate the correlation between the apparent diffusion coefficient values obtained by diffusion-weighted imaging and the key prognostic factors in breast invasive ductal carcinoma. Secondary objectives were to analyze the eventual correlations between magnetic resonance imaging findings and prognostic factors in breast cancer; and to perform a comparison between results in 1.5 and 3.0 T scanners. METHODS: Breast magnetic resonance imaging with diffusion-weighted imaging sequence was performed on 100 patients, who were proven histopathologically to have breast invasive ductal carcinoma. We compared the apparent diffusion coefficient values, obtained previous to biopsy, with the main prognostic factors in breast cancer: tumor size, histologic grade, hormonal receptors, Ki67 index, human epidermal growth factor receptor type 2, and axillary lymph node status. The Mann-Whitney U test and the Kruskal-Wallis analysis were used to establish these correlations. RESULTS: The mean apparent diffusion coefficient value was inferior in the estrogen receptor-positive group than in the estrogen receptor-negative group (1.04 vs 1.17 × 10-3 mm2/s, P = .004). Higher histologic grade related to larger tumor size (P = .002). We found association between spiculated margins and positive axillary lymph node status [odds ratio = 4.35 (1.49-12.71)]. There were no differences in apparent diffusion coefficient measurements between 1.5 and 3.0 T magnetic resonance imaging scanners (P = .513). CONCLUSIONS: Low apparent diffusion coefficient values are related with positive expression of estrogen receptor. Larger tumors and spiculated margins are associated to worse prognosis. Rim enhancement is more frequently observed in estrogen receptor-negative tumors. There are no differences in apparent diffusion coefficient measurements between different magnetic resonance imaging scanners.

Mortalidad de una cohorte de hombres con fractura de cadera por fragilidad en un sector sanitario: factores asociados / Mortality in a cohort of men with fragility hip fracture in a health area: associated factors

FUNDAMENTOS: Una cuarta parte de los pacientes con fractura de cadera por fragilidad (FCF) son hombres, y estos presentan una mortalidad mayor que las mujeres. El objetivo de este trabajo es estudiar la mortalidad consecuencia de la FCF en hombres ≥65años, tanto intrahospitalaria como al año y a los 3años, y los posibles factores asociados. MATERIAL Y MÉTODOS: Estudio observacional analítico de una cohorte histórica de 182 pacientes varones con FCF ≥65años ingresados en un servicio de Cirugía Ortopédica y Traumatología (COT) entre enero de 2009 y diciembre de 2014. RESULTADOS: La mortalidad intrahospitalaria fue del 10,9% (6% en el servicio COT y 8,6% en el centro sociosanitario). Se encontró asociación entre la mortalidad intrahospitalaria y la edad (p = 0,039). Veinte pacientes murieron durante su estancia en ambos hospitales. Cuarenta y dos (25,9%) murieron un año después y 95 (58,6%) murieron 3años después. La demencia/deterioro cognitivo se relacionó con un riesgo relativo de mortalidad a un año de 2,2, y de mortalidad a 3años de 1,6. Encontramos asociación entre la edad y la mortalidad y entre el índice de Barthel al inicio y la mortalidad en ambos períodos. Las causas más frecuentes de muerte fueron cardiovasculares (15,7%) y tumores (13,6%). CONCLUSIONES: Los varones con FCF presentaron una mortalidad elevada tanto intrahospitalaria, como al año y a los 3años. El factor de riesgo más determinante de mortalidad al año es la demencia/deterioro cognitivo, y el de mortalidad a los 3años, la HTA

BACKGROUND: A quarter of the patients with fragility hip fracture (FHF) are men, and they have higher mortality rates than women. The objective of this study is to analyse the mortality, as well as associated factors, due to FHF in men aged ≥65years, while in hospital and at one and three years of follow-up. MATERIAL AND METHODS: An analytical observational study was conducted on a historical cohort of 182 male patients equal or older than 65 years that were admitted to an Orthopaedic Surgery and Traumatology (OST) Department between January 2009 and December 2014. RESULTS: Within-hospital mortality was 10.9% (6% in the OST Department, and 8.6% in a Social-Health centre). A relationship (P=.039) was found between within-hospital mortality and age. A total of 20 patients died during their stay in both units, 42 (25.9%) died one year later, and 95 (58.6%) died three years later. Dementia/cognitive impairment was associated with a relative risk of one-year mortality of 2.2, and 1.6 of three-year mortality. An association was observed between age and mortality and between Barthel Index at baseline and mortality at both periods. The most frequent causes of death were cardiovascular (15.7%) and tumours (13.6%). CONCLUSIONS: Male patients with FHF showed high mortality rates in hospital, and at one-year and three-years follow-up. The most important risk factor of mortality was dementia/cognitive deterioration at one year, and high blood pressure at three years