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.

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.

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.

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.

Multiparametric magnetic resonance imaging-guided salvage radiotherapy in prostate cancer.

AIM: To analyse the efficacy and toxicity of postprostatectomy SRT in patients with a BCR evaluated with mpMRI. BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) has the ability to detect the site of pelvic recurrence in patients with biochemical recurrence (BCR) after radical prostatectomy (RP). However, we do not know the oncological outcomes of mpMRI-guided savage radiotherapy (SRT). RESULTS: Local, lymph node, and pelvic bone recurrence was observed in 13, 4 and 2 patients, respectively. PSA levels were significantly lower in patients with negative mpMRI (0.4 ng/mL [0.4]) vs. positive mpMRI (2.2 ng/mL [4.1], p = 0.003). Median planning target volume doses in patients with visible vs. non-visible recurrences were 76 Gy vs. 70 Gy. Overall, mean follow-up was 41 months (6-81). Biochemical relapse-free survival (bRFS) at 3 years was 82.3% and 82.5%, respectively, for the negative and positive mpMRI groups (p = 0.800). Three-year rates of late grade ≥2 urinary and rectal toxicity were 14.8% and 1.9%, respectively; all but one patient recovered without sequelae. CONCLUSION: SRT to the macroscopic recurrence identified by mpMRI is a feasible and well-tolerated option. In this study, there were no differences in bRFS between MRI-positive and MRI-negative patients, indicating effective targeting of MRI-positive lesions.

Antibody responses to influenza vaccine in patients on biological therapy: Results of RIER cohort study.

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.

A systematic follow-up protocol achieving a low hemodialysis graft thrombosis rate.

INTRODUCTION: Graft is an alternative to native arteriovenous fistula to ensure permanent vascular access in hemodialysis patients. The most common complication is significant stenosis, which frequently causes thrombosis and graft loss. Periodic monitoring and surveillance with elective correction of stenotic lesions can prolong graft survival. OBJECTIVE: To describe the effect of early diagnosis of significant stenosis on the rate of thrombosis and graft patency. METHODS: Retrospective, observational study of a cohort of 86 prevalent patients undergoing hemodialysis with a graft as their vascular access. We applied a systematic follow-up protocol of 115 grafts based on various screening methods of monitoring (clinical monitoring, pre-pump arterial pressure, dynamic venous pressure, percentage of recirculation, and dose of dialysis) in conjunction with surveillance (normalized intra-access venous pressure and access flow). The annual rates of thrombosis, and primary, primary-assisted, and secondary patency were assessed. RESULTS: The incidence of significant stenosis and thrombosis was 57.4% (65/115) and 39.0% (45/115), respectively. Of all screening procedures, normalized intra-access venous pressure was the best predictor of significant stenosis (hazards ratio, 7.71; 95% confidence interval, 3.06-19.46). The annual rate of thrombosis fluctuated from 0 to 0.26 thromboses/patient/year, with an average rate of 0.14 thromboses/patient/year. Primary, primary-assisted, and secondary patency were 74%/79%/82%, 50%/60%/66%, and 23%/35%/37% at 1, 2, and 5 years, respectively. CONCLUSION: The implementation of a systematic graft follow-up protocol combined with monitoring and surveillance enabled early diagnosis and elective correction of significant stenosis, prolonged graft patency, and a low thrombosis rate.

Preoperative diagnosis of atypical pelvic leiomyoma and sarcoma: the potential role of diffusion-weighted imaging.

The objective of our study was to determine the utility of diffusion-weighted magnetic resonance (DWMR) to differentiate the atypical uterine leiomyomas and sarcomas, establishing a cut-off value of the apparent diffusion coefficient (ADC) to rule out the malignancy. We performed a diagnostic accuracy retrospective study including 10 patients with pelvic sarcomas and 17 patients with leiomyomas. Atypical morphological features in magnetic resonance (MR) studies occurred in 58.8% of the patients, leading to a significant number of indeterminate diagnoses. In contrast, ADC values were consistent for leiomyomas, sarcomas, primary tumours, recurrences, intrauterine and in the extrauterine pelvic locations. The ADC cut-off value was set in 1 (×10-3 mm2/s). Thus, the ADC values equal or superior to 1 × 10-3 mm2/s were always associated with a leiomyoma. The structural MR accuracy was 66.7%, reaching 100% when using DWMR with dichotomised ADC values. Diffusion-weighted imaging with the quantitative measurement of ADC may be considered a useful preoperative test for the differentiation of atypical leiomyomas from sarcomas. Impact statement What is already known on this subject? Papers reporting the utility of a diffusion-weighted MR for the diagnosis of uterine sarcomas are scarce and consist of a small series. However, the published results are consistent with our study, with the decreased ADCs in the case of malignancy. What do the results of this study add? The main differential characteristic of our study is that we selected only the atypical leiomyomas: they share sonographic and MR features with sarcomas, which often leads to an inaccurate diagnosis. This is also the first paper reporting on the role of DWMR with ADC for these types of tumours in extrauterine pelvic locations. We demonstrated a consistent relationship between dichotomised ADC values in leiomyomas/sarcomas for these particular cases and in recurrent tumours, with no overlap between both the groups, as a difference with the previous reports. What are the implications of these findings for clinical practice and/or further research? Our study can be considered as a proof of concept supporting DWMR with ADC measurement as a useful tool to enhance the diagnostic accuracy of MR, highlighting its value to rule out malignancy. Hence, DWMR seems to be a potential useful test to include in the preoperative evaluation of clinically atypical uterine tumours.

Hyponatremia in children with pneumonia rarely means SIADH.

BACKGROUND: Hyponatremia (HN) < 135 mmol/L is a frequent finding in children with community-acquired pneumonia (CAP). We aimed to determine the proportion of syndrome of inappropriate antidiuretic hormone secretion (SIADH) among patients with CAP and HN. Moreover, we wished to investigate the relationship between HN and inflammatory markers, bacterial etiology and prognosis in hospitalized children with CAP. METHODS: We carried out a prospective, observational, multicentre, prospective cohort study. Eligible participants were children from 1 month to 17 years old hospitalized due to CAP from 2012 to 2015. RESULTS: A total of 150 children were analyzed. Forty-five (30%) patients had serum sodium levels of less than 135 mmol/L. Patients with HN had significantly higher concentrations of inflammatory biomarkers. They also had significantly lower osmolality and urine sodium. They also had longer hospitalizations and more days of fever. Only 16 out of the 45 (35%) patients with HN had confirmed calculated plasma osmolality (<275 mOsm/kg). Only 5 out of 37 (13%) patients with available measurements of plasma osmolality and urine sodium fulfilled the criteria for SIADH. Among the 16 patients with HN and hypo-osmolality, 15 had a fractional sodium excretion (EFNa) levels of less than 1%. We found a significant inverse linear correlation between serum sodium and C-reactive protein, as well as serum sodium and procalcitonin. We found a significant direct correlation between serum sodium and urine sodium. CONCLUSION: HN is a common finding in hospitalized children with CAP. True SIADH is a rare event. HN has a good correlation with inflammatory biomarkers.

Mirabegron, a Clinically Approved ß3 Adrenergic Receptor Agonist, Does Not Reduce Infarct Size in a Swine Model of Reperfused Myocardial Infarction.

The administration of the selective ß3 adrenergic receptor (ß3AR) agonist BRL-37344 protects from myocardial ischemia/reperfusion injury (IRI), although the lack of clinical approval limits its translatability. We tested the cardioprotective effect of mirabegron, the first-in-class ß3AR agonist approved for human use. A dose-response study was conducted in 6 pigs to select the highest intravenous dose of mirabegron without significant detrimental hemodynamic effect. Subsequently, closed chest anterior myocardial infarction (45 min ischemia followed by reperfusion) was performed in 26 pigs which randomly received either mirabegron (10 µg/kg) or placebo 5 min before reperfusion. Day-7 cardiac magnetic resonance (CMR) showed no differences in infarct size (35.0 ± 2.0% of left ventricle (LV) vs. 35.9 ± 2.4% in mirabegron and placebo respectively, p = 0.782) or LV ejection fraction (36.3 ± 1.1 vs. 34.6 ± 1.9%, p = 0.430). Consistent results were obtained on day-45 CMR. In conclusion, the intravenous administration of the clinically available selective ß3AR agonist mirabegron does not reduce infarct size in a swine model of IRI.