Stepwise application of ECG and electrogram-based criteria to ensure electrical resynchronization with left bundle branch pacing.

AIMS: To define a stepwise application of left bundle branch pacing (LBBP) criteria that will simplify implantation and guarantee electrical resynchronization. Left bundle branch pacing has emerged as an alternative to biventricular pacing. However, a systematic stepwise criterion to ensure electrical resynchronization is lacking. METHODS AND RESULTS: A cohort of 24 patients from the LEVEL-AT trial (NCT04054895) who received LBBP and had electrocardiographic imaging (ECGI) at 45 days post-implant were included. The usefulness of ECG- and electrogram-based criteria to predict accurate electrical resynchronization with LBBP were analyzed. A two-step approach was developed. The gold standard used to confirm resynchronization was the change in ventricular activation pattern and shortening in left ventricular activation time, assessed by ECGI. Twenty-two (91.6%) patients showed electrical resynchronization on ECGI. All patients fulfilled pre-screwing requisites: lead in septal position in left-oblique projection and W paced morphology in V1. In the first step, presence of either right bundle branch conduction delay pattern (qR or rSR in V1) or left bundle branch capture Plus (QRS ≤120 ms) resulted in 95% sensitivity and 100% specificity to predict LBBP resynchronization, with an accuracy of 95.8%. In the second step, the presence of selective capture (100% specificity, only 41% sensitivity) or a spike-R <80 ms in non-selective capture (100% specificity, sensitivity 46%) ensured 100% accuracy to predict resynchronization with LBBP. CONCLUSION: Stepwise application of ECG and electrogram criteria may provide an accurate assessment of electrical resynchronization with LBBP (Graphical abstract).

Determinants of the current and future distribution of the West Nile virus mosquito vector Culex pipiens in Spain.

Changes in environmental conditions, whether related or not to human activities, are continuously modifying the geographic distribution of vectors, which in turn affects the dynamics and distribution of vector-borne infectious diseases. Determining the main ecological drivers of vector distribution and how predicted changes in these drivers may alter their future distributions is therefore of major importance. However, the drivers of vector populations are largely specific to each vector species and region. Here, we identify the most important human-activity-related and bioclimatic predictors affecting the current distribution and habitat suitability of the mosquito Culex pipiens and potential future changes in its distribution in Spain. We determined the niche of occurrence (NOO) of the species, which considers only those areas lying within the range of suitable environmental conditions using presence data. Although almost ubiquitous, the distribution of Cx. pipiens is mostly explained by elevation and the degree of urbanization but also, to a lesser extent, by mean temperatures during the wettest season and temperature seasonality. The combination of these predictors highlights the existence of a heterogeneous pattern of habitat suitability, with most suitable areas located in the southern and northeastern coastal areas of Spain, and unsuitable areas located at higher altitude and in colder regions. Future climatic predictions indicate a net decrease in distribution of up to 29.55%, probably due to warming and greater temperature oscillations. Despite these predicted changes in vector distribution, their effects on the incidence of infectious diseases are, however, difficult to forecast since different processes such as local adaptation to temperature, vector-pathogen interactions, and human-derived changes in landscape may play important roles in shaping the future dynamics of pathogen transmission.

House sparrow uropygial gland secretions do not attract ornithophilic nor mammophilic mosquitoes.

Mosquito feeding preferences determine host-vector contact rates and represent a key factor in the transmission of vector-borne pathogens. The semiochemical compounds of which vertebrate odours are composed probably play a role in mosquito host choice. Birds spread secretions from uropygial gland over their feathers to protect their plumage, comprising behaviour that may in turn affect odour profiles. Although uropygial secretions are expected to modify the attractiveness of birds to mosquitoes, contradictory findings have been reported. Mosquito species differ in their feeding preferences, with some species feeding mainly on birds (ornithophilic species) and others on mammals (mammophilic species). Consequently, it is possible that ornithophilic and mammophilic species differ in their response to uropygial gland secretions. Using a dual-choice olfactometer, the present study tests this hypothesis by comparing the behavioural response to uropygial gland secretions from juvenile male and female house sparrows (Passer domesticus) in the ornithophilic Culex pipiens and the mammophilic Aedes (Ochlerotatus) caspius mosquitoes. No differences were found in the response of either mosquito species to the uropygial gland secretions. Therefore, the preference of ornithophilic mosquitoes for avian hosts is apparently not explained by a greater attraction of mosquitoes to the uropygial gland secretion odour when presented in combination with a CO2 -enriched airflow.

A spatial ecology study in a high-diversity host community to understand blood-feeding behaviour in Phlebotomus sandfly vectors of Leishmania.

Molecular studies indicate that Phlebotomine sandflies (Diptera: Psychodidae) blood feed on many vertebrate species, of which only a few are proven parasite reservoirs. Investigating sandfly vector feeding preferences is therefore important and requires taking into account the availability and accessibility of host species. In terms of the latter, it is necessary to consider the metabolic cost to the insect of reaching the host and moving on to a suitable breeding site. The present study used statistical modelling to compare the feeding patterns of Phlebotomus perniciosus (n = 150), Phlebotomus papatasi (n = 35) and Phlebotomus ariasi (n = 7) on each of an average of 30 host species in a wildlife park in Murcia, Spain. Sandfly feeding movement costs were estimated as a function of the distance and altitude gradients saved by the insect, assuming that they displayed 'site fidelity'. Most (87%) engorged females were caught <100 m from the host on which they had fed. Although the percentage of bloodmeals was highest on fallow deer (Dama dama) (30%) and red deer (Cervus elaphus) (26%), the predicted feeding probability after considering movement cost was highest for red deer and common eland (Taurotragus oryx), and positively associated with host census. These results suggest that, under similar circumstances, sandflies prefer to feed on some host species more than on others.

Correction to: Persistent major alopecia following adjuvant docetaxel for breast cancer: incidence, characteristics, and prevention with scalp cooling.

In the original publication of the article, Table 1 was published with incorrect caption and values. The Table 1 with corrected caption and values is given in this Correction.

Persistent major alopecia following adjuvant docetaxel for breast cancer: incidence, characteristics, and prevention with scalp cooling.

BACKGROUND: Persistent alopecia (PA) after docetaxel has been recently described. The aim of our study is to establish the incidence and characteristics of PA following adjuvant docetaxel for breast cancer (BC) and to test the ability of scalp cooling in prevention. PATIENTS AND METHODS: BC patients receiving adjuvant chemotherapy followed or not by endocrine therapy (and a control group receiving only endocrine therapy) were interviewed in a single institution at 1.5 to 5 years following primary diagnosis searching for PA. A confirmatory prevalence study was later performed in other two institutions. Finally, a prevention study using prophylactic scalp cooling (PSC) with ELASTO-GEL hypothermia caps in patients receiving adjuvant docetaxel was performed. RESULTS: In the initial prevalence study (492 patients), minor forms of PA (grade 1) were recorded with all chemotherapy regimens and aromatase inhibitors. Patients receiving docetaxel regimens at cumulative dose (CD) ≥ 400 mmg/m2 presented a significantly higher prevalence of grades 1 PA (33-52%) and 2 PA (5-12%). Prevalence of grade 2 PA with docetaxel CD ≥ 400 mmg/m2 was confirmed in two other institutions. Overall, grade 2 PA was seen in 10.06% (95% CI 7.36-13.61) of 358 patients with docetaxel regimens reaching CD ≥ 400 mmg/m2, but not in patients with lower docetaxel CD, other chemotherapy regimens, or endocrine therapy alone. In prevention trial, no grade 2 PA occurred among 116 patients receiving adjuvant docetaxel (≥ 400 mmg/m2) and PSC followed-up after a 96 months median time. PSC was well tolerated. No scalp relapses were seen among 30 patients (22% of all inclusions) having disease relapse. CONCLUSION: Adjuvant treatment with docetaxel (CD ≥ 400 mmg/m2) is associated with a significant rate of grade 2 PA, leading to wearing a wig, in around 10% of patients. This toxicity was completely prevented with scalp cooling. Clinical Trial Reference: NCT00515762.

The contribution of dogs and other animals to social inclusion programmes. / Contribución de los perros y otros animales en programas destinados a la inclusión social.

Animal-assisted interventions refer to any intervention that intentionally includes or incorporates animals as part of a therapeutic, palliative, educational, psychoeducational or recreational process or milieu. The Faculty of Veterinary Science of the University of Buenos Aires began work on this issue in 1996 and gradually incorporated outreach, research and teaching projects, undertaking several stages of institutionalisation and reconceptionalisation that led, in 2014, to the creation of an open chair in animal-assisted interventions. This article aims to introduce the discipline, with special emphasis on its potential as a means of promoting inclusion, and to present a specific case of work with dogs, which began in 2009 with the non-profit organisation Senderos del Sembrador (Trails of the Sower) for people with an intellectual disability who are in great need of support. This article describes how the contact with dogs was systematised, along with outcomes, challenges and difficulties, and how leisure came to be used as a means of promoting inclusion and altering the preconceptions of people without disabilities. Finally, in reflecting on practices, the project evolved from a treatment plan for rehabilitating people with disabilities into a space for effective social inclusion that gradually changed the perceptions and practices of all participants.

Les interventions assistées par des animaux désignent toute intervention intégrant de manière intentionnelle des animaux en tant qu'acteurs au sein d'un processus thérapeutique, palliatif, pédagogique, psycho-éducatif, ludique ou environnemental. La faculté des Sciences vétérinaires de l'université de Buenos Aires a commencé à explorer ce domaine dès 1996, en y ajoutant progressivement des projets d'application locale, de recherche et d'enseignement qui ont connu plusieurs phases successives d'institutionnalisation et de conceptualisation avant d'aboutir en 2014 à la création d'une chaire autonome d'interventions assistées par l'animal. Après avoir introduit cette discipline en mettant un accent particulier sur ses perspectives en tant que facteur d'inclusion, les auteurs décrivent une expérience concrète d'interventions menées depuis 2009 avec des chiens auprès d'une association de la société civile (« Senderos del Sembrador ¼) qui s'occupe de personnes ayant des déficiences intellectuelles et qui ont un grand besoin d'aide. Les auteurs expliquent le recours systématique à ce contact, ainsi que ses résultats, ses enjeux et ses difficultés, et l'utilisation des loisirs comme facteur d'inclusion parallèlement à la lutte contre les préjugés chez les personnes non handicapées. Enfin, à travers les ateliers proposés, ce projet a constitué une authentique proposition thérapeutique qui a donné aux personnes handicapées les outils nécessaires pour constituer un espace d'inclusion sociale efficace, qui a progressivement transformé les conceptions et les pratiques de tous les participants.

Las intervenciones asistidas con animales son cualquier intervención que intencionalmente incluya o incorpore animales como parte de un proceso terapéutico, paliativo, pedagógico, psicoeducativo, lúdico o ambiental. La Facultad de Ciencias Veterinarias de la Universidad de Buenos Aires comenzó a trabajar en este tema en 1996, e incorporó paulatinamente proyectos de extensión, investigación y docencia atravesando diversas etapas de institucionalización y reconceptualización, hasta que en 2014 se creó la Cátedra Libre de Intervenciones Asistidas con Animales. El objetivo de este trabajo es introducir esta disciplina, con especial énfasis en sus posibilidades como factor de inclusión, y presentar una experiencia concreta de trabajo con perros que se realiza desde 2009 con la Asociación Civil Senderos del Sembrador, a la que concurren personas con discapacidad intelectual y una gran necesidad de apoyo. Relatamos cómo hemos sistematizado este contacto, sus resultados, desafíos y dificultades, y cómo hemos podido trabajar el ocio como factor de inclusión además de actuar sobre los prejuicios de las personas sin discapacidad. Finalmente, en cuanto a las prácticas, este proyecto pasó de ser una propuesta terapéutica para rehabilitar a las personas con discapacidad a constituir un espacio de inclusión social efectiva que fue modificando las concepciones y prácticas de todos los participantes.

Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study.

BACKGROUND: There is an urgent need to identify biomarkers to guide personalized therapy in castration-resistant prostate cancer (CRPC). We aimed to clinically qualify androgen receptor (AR) gene status measurement in plasma DNA using multiplex droplet digital PCR (ddPCR) in pre- and post-chemotherapy CRPC. METHODS: We optimized ddPCR assays for AR copy number and mutations and retrospectively analyzed plasma DNA from patients recruited to one of the three biomarker protocols with prospectively collected clinical data. We evaluated associations between plasma AR and overall survival (OS) and progression-free survival (PFS) in 73 chemotherapy-naïve and 98 post-docetaxel CRPC patients treated with enzalutamide or abiraterone (Primary cohort) and 94 chemotherapy-naïve patients treated with enzalutamide (Secondary cohort; PREMIERE trial). RESULTS: In the primary cohort, AR gain was observed in 10 (14%) chemotherapy-naïve and 33 (34%) post-docetaxel patients and associated with worse OS [hazard ratio (HR), 3.98; 95% CI 1.74-9.10; P < 0.001 and HR 3.81; 95% CI 2.28-6.37; P < 0.001, respectively], PFS (HR 2.18; 95% CI 1.08-4.39; P = 0.03, and HR 1.95; 95% CI 1.23-3.11; P = 0.01, respectively) and rate of PSA decline ≥50% [odds ratio (OR), 4.7; 95% CI 1.17-19.17; P = 0.035 and OR, 5.0; 95% CI 1.70-14.91; P = 0.003, respectively]. AR mutations [2105T>A (p.L702H) and 2632A>G (p.T878A)] were observed in eight (11%) post-docetaxel but no chemotherapy-naïve abiraterone-treated patients and were also associated with worse OS (HR 3.26; 95% CI 1.47-not reached; P = 0.004). There was no interaction between AR and docetaxel status (P = 0.83 for OS, P = 0.99 for PFS). In the PREMIERE trial, 11 patients (12%) with AR gain had worse PSA-PFS (sPFS) (HR 4.33; 95% CI 1.94-9.68; P < 0.001), radiographic-PFS (rPFS) (HR 8.06; 95% CI 3.26-19.93; P < 0.001) and OS (HR 11.08; 95% CI 2.16-56.95; P = 0.004). Plasma AR was an independent predictor of outcome on multivariable analyses in both cohorts. CONCLUSION: Plasma AR status assessment using ddPCR identifies CRPC with worse outcome to enzalutamide or abiraterone. Prospective evaluation of treatment decisions based on plasma AR is now required. CLINICAL TRIAL NUMBER: NCT02288936 (PREMIERE trial).

First molecular identification of the vertebrate hosts of Culicoides imicola in Europe and a review of its blood-feeding patterns worldwide: implications for the transmission of bluetongue disease and African horse sickness.

Culicoides (Diptera: Ceratopogonidae) are vectors of pathogens that affect wildlife, livestock and, occasionally, humans. Culicoides imicola (Kieffer, 1913) is considered to be the main vector of the pathogens that cause bluetongue disease (BT) and African horse sickness (AHS) in southern Europe. The study of blood-feeding patterns in Culicoides is an essential step towards understanding the epidemiology of these pathogens. Molecular tools that increase the accuracy and sensitivity of traditional methods have been developed to identify the hosts of potential insect vectors. However, to the present group's knowledge, molecular studies that identify the hosts of C. imicola in Europe are lacking. The present study genetically characterizes the barcoding region of C. imicola trapped on farms in southern Spain and identifies its vertebrate hosts in the area. The report also reviews available information on the blood-feeding patterns of C. imicola worldwide. Culicoides imicola from Spain feed on blood of six mammals that include species known to be hosts of the BT and AHS viruses. This study provides evidence of the importance of livestock as sources of bloodmeals for C. imicola and the relevance of this species in the transmission of BT and AHS viruses in Europe.

New advances in genitourinary cancer: evidence gathered in 2014.

This review provides updated information published in 2014 regarding advances and major achievements in genitourinary cancer. Sections include the best in prostate cancer, renal cancer, bladder cancer, and germ cell tumors. In the field of prostate cancer, data related to treatment approach of hormone-sensitive disease, castrate-resistant prostate cancer, mechanisms of resistance, new drugs, and molecular research are presented. In relation to renal cancer, relevant aspects in the treatment of advanced renal cell carcinoma, immunotherapy, and molecular research, including angiogenesis and von Hippel-Lindau gene, molecular biology of non-clear cell histologies, and epigenetics of clear renal cell cancer are described. New strategies in the management of muscle-invasive localized bladder cancer and metastatic disease are reported as well as salient findings of biomolecular research in urothelial cancer. Some approaches intended to improve outcomes in poor prognosis patients with metastatic germ cell cancer are also reported. Results of clinical trials in these areas are discussed.

Adenomyosis in infertile women: prevalence and the role of 3D ultrasound as a marker of severity of the disease.

BACKGROUND: Adenomyosis is linked to infertility, but the mechanisms behind this relationship are not clearly established. Similarly, the impact of adenomyosis on ART outcome is not fully understood. Our main objective was to use ultrasound imaging to investigate adenomyosis prevalence and severity in a population of infertile women, as well as specifically among women experiencing recurrent miscarriages (RM) or repeated implantation failure (RIF) in ART. METHODS: Cross-sectional study conducted in 1015 patients undergoing ART from January 2009 to December 2013 and referred for 3D ultrasound to complete study prior to initiating an ART cycle, or after ≥3 IVF failures or ≥2 miscarriages at diagnostic imaging unit at university-affiliated private IVF unit. Adenomyosis was diagnosed in presence of globular uterine configuration, myometrial anterior-posterior asymmetry, heterogeneous myometrial echotexture, poor definition of the endometrial-myometrial interface (junction zone) or subendometrial cysts. Shape of endometrial cavity was classified in three categories: 1.-normal (triangular morphology); 2.- moderate distortion of the triangular aspect and 3.- "pseudo T-shaped" morphology. RESULTS: The prevalence of adenomyosis was 24.4 % (n = 248) [29.7 % (94/316) in women aged ≥40 y.o and 22 % (154/699) in women aged <40 y.o., p = 0.003)]. Its prevalence was higher in those cases of recurrent pregnancy loss [38.2 % (26/68) vs 22.3 % (172/769), p < 0.005] and previous ART failure [34.7 % (107/308) vs 24.4 % (248/1015), p < 0.0001]. The presence of adenomyosis has been shown to be associated to endometriosis [35.1 % (34/97)]. Adenomyosis was diagnosed as a primary finding "de novo" in 80.6 % (n = 200) of the infertile patients. The impact on the uterine cavity was mild, moderate and severe in 63.7, 22.6 and 10.1 % of the cases, respectively. CONCLUSIONS: Our results indicate that adenomyosis is a clinical condition with a high prevalence that may affect the reproductive results. The described severity criteria may help future validating studies for better counseling of infertile couples.

West Nile virus-neutralizing antibodies in wild birds from southern Spain.

West Nile virus (WNV) is an emerging vector-borne arbovirus with a zoonotic life-cycle whose main reservoir hosts are birds. In humans and horses, WNV infections rarely result in clinical disease but on occasions - depending on factors such as climatic conditions, insect communities and background immunity levels in local populations - they can lead to outbreaks that threaten public and animal health. We tested for the presence of WNV antibodies in 149 birds belonging to 32 different species. Samples were first tested using a bird-specific ELISA kit and then both positive and doubtful results were confirmed by neutralization tests using WNV and Usutu virus. WNV antibodies were confirmed in a resident Sylvia melanocephala juvenile, supporting the idea of local transmission of WNV in southern Spain in 2013. In addition, the serum from an adult blackbird (Turdus merula) showed neutralization of both WNV and Usutu virus. We discuss our results in light of the occurrence of WNV on horse farms in southern Spain in 2013.

Telomere dynamics in parasitic great spotted cuckoos and their magpie hosts.

Although little is known on the impact of environment on telomere length dynamics, it has been suggested to be affected by stress, lifestyle and/or life-history strategies of animals. We here compared telomere dynamics in erythrocytes of hatchlings and fledglings of the brood parasite great spotted cuckoos (Clamator glandarius) and of magpies (Pica pica), their main host in Europe. In magpie chicks, telomere length decreased from hatching to fledging, whereas no significant change in telomere length of great spotted cuckoo chicks was found. Moreover, we found interspecific differences in the association between laying date and telomere shortening. Interspecific differences in telomere shortening were interpreted as a consequence of differences in lifestyle and life-history characteristics of magpies and great spotted cuckoos. In comparison with magpies, cuckoos experience reduced sibling competition and higher access to resources and, consequently, lower stressful environmental conditions during the nestling phase. These characteristics also explain the associations between telomere attrition and environmental conditions (i.e. laying date) for magpies and the absence of association for great spotted cuckoos. These results therefore fit expectations on telomere dynamics derived from interspecific differences in lifestyle and life history of brood parasites and their bird hosts.

Older type 2 diabetic patients are more likely to achieve glycaemic and cardiovascular risk factors targets than younger patients: analysis of a primary care database.

BACKGROUND: Older subjects with type 2 diabetes mellitus (T2DM) have differential characteristics compared with middle-aged or younger populations, and require tailored management of the disease. AIMS: To evaluate how clinical characteristics, degree of control of glycaemia and cardiovascular risk factors, presence of chronic complications and treatments differ between older T2DM patients and younger adults. METHODS: Cross-sectional study using data from a population-based electronic database. We retrieved data from 318,020 patients ≥ 30 years diagnosed with T2DM, attended during 2011 in primary care centres in Catalonia, Spain. We performed descriptive and comparative analyses stratified by gender and age subgroups: ≤ 65, 66-75, 76-85 and >85 years. RESULTS: Both men and women across older age subgroups (> 65 years) had longer diabetes duration than younger adults (8.0 vs. 5.6 in men and 8.4 vs. 6.9 years in women; p < 0.001), but better glycaemic control (mean glycated haemoglobin 7.1 vs. 7.7 in men and 7.1 vs. 7.4 in women; p < 0.001), and better combined control of different cardiovascular risk factors (p < 0.001). Moreover, older patients were more likely to achieve glycaemic targets irrespective of having cardiovascular disease. The use of oral antidiabetics decreased with increasing age, and insulin in monotherapy was more frequently prescribed among patients in the older age subgroups. Diabetes-related complications were more frequent in men of all group ages. In the older age subgroups, patients of both sexes had a longer duration of T2DM but better glycaemic control. In this context, the prevalence of diabetic retinopathy decreased unexpectedly with increasing age. CONCLUSION: Control of glycaemia and cardiovascular risk factors was better among older T2DM patients. There is a need for prospective studies to quantify the weight of risk factors in each complication to adapt the therapeutic and care approaches in elderly people.

Bicarbonate enhances the in vitro antibiotic activity of kanamycin in Escherichia coli.

UNLABELLED: Growth of enteropathogenic Escherichia coli E2348/69 was inhibited by bicarbonate in a dose-dependent manner, showing approximately 5% growth reduction at 5 mmol l(-1) while kanamycin at 3·12 µg ml(-1) inhibited growth by 15%, yet when kanamycin and bicarbonate were combined at these concentrations, inhibition increased to 80%. Unexpectedly, at bicarbonate concentrations >20 mmol l(-1) enhancement of the antibiotic activity virtually disappeared, i.e. there was a paradoxical Eagle-like effect. How bicarbonate acts is unclear, but neutral or alkaline pH also enhanced the activity of kanamycin. However, several differences indicated a separate effect of bicarbonate. First, bicarbonate inhibited growth more than the corresponding increments in pH. Second, at low concentration, the antibiotic enhancing effect of bicarbonate was stronger than the effect of pH alone. Third, 5 mmol l(-1) bicarbonate significantly enhanced the activity of kanamycin while the corresponding pH had no effect. Fourth, the Eagle-like effect was exclusive of bicarbonate because changes in pH did not induce an analogous behaviour. Notwithstanding the mechanism, the enhancing effect of bicarbonate was indubitable. Consequently, it seems worthwhile to explore further its potential to improve the efficacy of aminoglycosides and maybe even other antibiotics. SIGNIFICANCE AND IMPACT OF THE STUDY: Bicarbonate at a low concentration enhanced the in vitro antibiotic activity of kanamycin and gentamicin. Even though the action mechanism of bicarbonate is hitherto unknown, it seems worthwhile to explore further its capacity to improve the efficacy of aminoglycosides. Clearly, the well-known harmful side-effects of aminoglycosides are a concern. However, it has recently been shown in a fish model that bicarbonate may protect ciliary cells against the damage caused by aminoglycosides. So, it seems possible that bicarbonate could help reduce aminoglycoside dosage at the same time that it might help lessen the damage to auditory ciliary cells in humans.

[Recommendations for radiological diagnosis and assessment of treatment response in lung cancer: a national consensus statement by the Spanish Society of Medical Radiology and the Spanish Society of Medical Oncology]. / Recomendaciones para el diagnóstico radiológico y la valoración de la respuesta terapéutica en el cáncer de pulmón. Consenso nacional de la Sociedad Española de Radiología Médica y la Sociedad Española de Oncología Médica.

The last decade has seen substantial progress in the diagnostic and therapeutic approach to lung cancer, thus meaning that its prognosis has improved. The Spanish Society of Medical Radiology (SERAM) and the Spanish Society of Medical Oncology (SEOM) have therefore produced a national consensus statement in order to make recommendations for radiological diagnosis and assessment of treatment response in patients with lung cancer. This expert group recommends multi-detector computed tomography (MDCT) as the technique of choice for investigating this disease. The radiology report should include a full assessment by the TNM staging system. Lastly, when the patient is on immunotherapy, response evaluation should employ not only Response Evaluation Criteria in Solid Tumours (RECIST 1.1) but also Immune-Related Response Criteria (irRC).

Prospective study assessing hypoxia-related proteins as markers for the outcome of treatment with sunitinib in advanced clear-cell renal cell carcinoma.

BACKGROUND: Previous studies suggest that expression of hypoxia markers may be associated with response to antiangiogenic drugs. Thus, we aimed to identify predictors of sunitinib outcome in clear-cell renal cell carcinoma (ccRCC). PATIENTS AND METHODS: The expression of eight key proteins related to hypoxia (CAIX, HIF1A, HIF2A, VEGFA, VEGFR1, VEGFR2, VEGFR3 and PDGFRB) and P-glycoprotein were assessed by immunohistochemistry in 67 primary ccRCC samples from prospectively recruited patients treated with first-line sunitinib. The proteins expression, VHL inactivation and EGLN3 mRNA content were compared with the patients' response to sunitinib. RESULTS: High expression of HIF2A and PDGFRB was associated with better sunitinib RECIST objective response (P = 0.024 and P = 0.026; respectively) and increased VEGFR3 expression was associated with longer progression-free survival (P = 0.012). VEGFR3 overexpression showed a negative correlation with VEGFR3 polymorphism rs307826 (P = 0.002), a sunitinib resistance predictor. With respect to overall survival (OS), high VEGFA was associated with short (P = 0.009) and HIF2A with long (P = 0.048) survival times. High EGLN3 mRNA content was associated with shorter OS (P = 0.023). CONCLUSIONS: We found an association between several proteins involved in hypoxia and sunitinib efficacy. In addition, low VEGFR3 expression was associated with worse outcome and with VEGFR3 rs307826 variant allele, reinforcing VEGFR3 as a marker of sunitinib resistance.

Erlotinib versus pemetrexed for pretreated non-squamous non-small cell lung cancer patients in clinical practice.

BACKGROUND/AIM: Erlotinib and chemotherapy have shown similar efficacy for pretreated non-small cell lung cancer (NSCLC) patients, but none of the large studies have selected patients based on histology. We present a retrospective single-center series of advanced non-squamous NSCLC patients treated with erlotinib or pemetrexed as second-line therapy. Our aim was to compare the efficacy and safety data under clinical practice conditions and to identify subgroups of patients who could benefit more from these therapies. METHODS: A total of 88 patients were included. Squamous histology was our main exclusion criterion. EGFR mutation status was known for 54.5% of the patients; 6 patients treated with erlotinib and 2 with pemetrexed had EGFR-mutated tumors. Smoking history was analyzed as possible predictive factor of efficacy. RESULTS: No significant differences in progression-free survival (PFS; 3 vs. 2.5 months, p = 0.06) or overall survival (OS; 4.9 vs. 7.4 months, p = 0.733) between the erlotinib and pemetrexed groups were found in the overall population. EGFR wild-type patients had a similar median PFS with erlotinib compared to pemetrexed (2.7 vs. 2.3 months, p = 0.42), with no statistical differences in OS. Statistically significant differences in OS in favor of pemetrexed for current smokers (3 vs. 7.1 months, p = 0.017) were found, while erlotinib achieved significantly better PFS in never-smokers compared to former smokers (3.5 vs. 2.7 months, p = 0.005). Serious adverse events were uncommon but more frequent with pemetrexed, and were mainly related to hematologic toxicity. CONCLUSIONS: Erlotinib should be considered as another equal option in second-line treatment for EGFR wild-type patients as well as for subpopulations with unknown mutational status. Smoking history could be a useful clinical marker to choose a second-line treatment.

Vector abundance determines Trypanosoma prevalence in nestling blue tits.

The effect of insect vectors on avian exposure to infection by pathogens remains poorly studied. Here, we used an insect repellent treatment to reduce the number of blood-sucking flying insects in blue tit Cyanistes caeruleus nests and examined its effect on nestling health status measured as body mass, nestling phytohaemagglutinin (PHA) response and blood parasite prevalence. We found that (i) the insect repellent treatment significantly reduced the number of blood-sucking flying insects in nests and (ii) the number of blood-sucking flying insects had a significant effect on the prevalence of the blood parasite Trypanosoma independently of the treatment. In addition, we found support for an adverse effect of parasite infections on nestling PHA response. Nestlings infected by Trypanosoma mounted a weaker response against PHA than non-parasitized ones. In addition, the number of blowflies in the nest was negatively associated with nestling PHA response. Overall, we found support for the hypothesis that blood-sucking flying insects attacking nestlings increase their exposure to parasite infections. Our results further substantiate the adverse effect of parasites on nestling condition.