Anaesthetic-surgical guide in the treatment of ascending aorta and surgery of the ascending aorta and aortic arch. Consensus document of the Spanish Society of Cardiovascular and Endovascular Surgery and the Sociedad of Anaesthesiology, Resuscitation and Pain Therapy.

Aortic pathology is always a challenge for the clinician, and must be diagnosed and treated by a multidisciplinary team due to the technical and technological complexity of the resources used. Ongoing efforts to implement a systematic, protocolized approach involving "Aortic teams" made up of cardiologists, cardiac surgeons, vascular surgeons, anaesthesiologists and radiologists, among others are now leading to improved outcomes. The aim of this consensus document drawn up by the Aortic working groups of the Spanish Society of Anaesthesiology, Resuscitation and Pain Therapy (SEDAR) and the Spanish Society of Thoracic and Cardiovascular Surgery (SECTCV) is to disseminate a set of working protocols. The latest consensus document of the European Association for Cardio-Thoracic Surgery (EACTS) and the European Society for Vascular Surgery (ESVS) define the concept of "AORTIC TEAM"(1). The aortic team should be closely involved from diagnosis to treatment and finally follow-up, and should be formed of cardiac and vascular surgeons working together with anaesthesiologists, cardiologists, radiologists and geneticists. Treatment of aortic pathologies should be centralised in large centres, because this is the only way to effectively understand the natural course of the disease, provide the entire range of treatment options under one umbrella and treat potential complications. A streamlined emergent care pathway (24/7 availability), adequate transportation and transfer capabilities, as well as rapid activation of the multidisciplinary team must be available. In light of the complexity and constant evolution of therapeutic options, we present this first version of the Anaesthesiology and surgical guidelines for surgery of the ascending aorta and aortic arch. Some questions will no doubt remain unanswered, and future versions will include new techniques that, though implemented in some centres, are still not widely recommended.

Guía anestésico-quirúrgica en el tratamiento de la cirugía de aorta ascendente y del arco aórtico. Documento de consenso de la Sociedad Española de Cirugía Cardiovascular y Endovascular y la Sociedad Española de Anestesiología, Reanimación y Terapeútica del Dolor / Anaesthetic-surgical guide in the treatment of ascending aorta and surgery of the ascending aorta and aortic arch. Consensus document of the Spanish Society of Cardiovascular and Endovascular Surgery and the Sociedad of Anaesthesiology, Resuscitation and Pain Therapy

La patología de la aorta siempre supone un reto para la medicina. Tanto para sudiagnóstico como para su tratamiento, dicha patología requiere ser abordada de forma multidisciplinar debido a la complejidad técnica y tecnológica de los medios empleados. Gracias a los esfuerzos durante años se están obteniendo frutos en forma de mejora de resultados, mediante un abordaje sistemático y protocolizado llevado acabo en el seno de un grupo de expertos (Comités de aorta o “Aortic team”) en el quese implican cardiólogos, cirujanos cardíacos, cirujanos vasculares, anestesiólogos y radiólogos, entre otros. Con este documento, realizado entre los grupos de trabajo de Aorta de la Sociedad Española de Anestesiología, Reanimación y Terapéutica del dolor (SEDAR) y la Sociedad Española de Cirugía Torácica y Cardiovascular (SECTCV) se busca difundir protocolos de trabajo consensuados por ambas sociedades. La EACTS y la ESVS en el último documento de consenso de expertos definen el concepto de “AORTIC TEAM”(1). El equipo debe estar estrechamente involucrado en todo el proceso de diagnóstico, tratamiento y seguimiento y debe estar compuesto por miembros de cirugía cardiovascular en colaboración con anestesiología, cardiología, radiología y genética. Se recomienda la centralización de la atención de las patologías del arco aórtico en grandes centros porque es la única forma de comprender de manera efectiva el curso natural de la enfermedad, proporcionar toda la gama de opciones de tratamiento bajo un mismo prisma y tratar las posibles complicaciones. Debe estar disponible una vía simplificada de atención de emergencias (con disponibilidad 24h al día y 7 días a la semana), una adecuada capacidad de transporte y transferencia de pacientes, así como la posibilidad de una activación rápida del equipo multidisciplinar.(AU)

Aortic pathology is always a challenge for the clinician, and must be diagnosed and treated by a multidisciplinary team due to the technical and technological complexity of the resources used. Ongoing efforts to implement a systematic, protocolized approach involving “Aortic teams” made up of cardiologists, cardiac surgeons, vascular surgeons, anaesthesiologists and radiologists, among others are now leading to improved outcomes. The aim of this consensus document drawn up by the Aortic working groups of the Spanish Society of Anaesthesiology, Resuscitation and Pain Therapy (SEDAR) and the Spanish Society of Thoracic and Cardiovascular Surgery (SECTCV) is to disseminate a set of working protocols. The latest consensus document of the European Association for Cardio-Thoracic Surgery (EACTS) and the European Society for Vascular Surgery (ESVS) define the concept of “AORTIC TEAM”(1). The aortic team should be closely involved from diagnosis to treatment and finally follow-up, and should be formed of cardiac and vascular surgeons working together with anaesthesiologists, cardiologists, radiologists and geneticists. Treatment of aortic pathologies should be centralised in large centres, because this is the only way to effectively understand the natural course of the disease, provide the entire range of treatment options under one umbrella and treat potential complications. A streamlined emergent care pathway (24/7 availability), adequate transportation and transfer capabilities, as well as rapid activation of the multidisciplinary team must be available. In light of the complexity and constant evolution of therapeutic options, we present this first version of the Anaesthesiology and surgical guidelines for surgery of the ascending aorta and aortic arch. Some questions will no doubt remain unanswered, and future versions will include new techniques that, though implemented in some centres, are still not widely recommended.(AU)

Microbial Diversity of Adult Aedes aegypti and Water Collected from Different Mosquito Aquatic Habitats in Puerto Rico.

Mosquitoes, the major vectors of viruses like dengue, are naturally host to diverse microorganisms, which play an important role in their development, fecundity, immunity, and vector competence. The composition of their microbiota is strongly influenced by the environment, particularly their aquatic larval habitat. In this study, we used 2×300 bp 16s Illumina sequencing to compare the microbial profiles of emerging adult Aedes aegypti mosquitoes and the water collected from common types of aquatic habitat containers in Puerto Rico, which has endemic dengue transmission. We sequenced 141 mosquito and 46 water samples collected from plastic containers, septic tanks, discarded tires, underground trash cans, tree holes, or water meters. We identified 9 bacterial genera that were highly prevalent in the mosquito microbiome, and 77 for the microbiome of the aquatic habitat. The most abundant mosquito-associated bacterial OTUs were from the families Burkholderiaceae, Pseudomonadaceae, Comamonadaceae, and Xanthomonadaceae. Microbial profiles varied greatly between mosquitoes, and there were few major differences explained by container type; however, the microbiome of mosquitoes from plastic containers was more diverse and contained more unique taxa than the other groups. Container water was significantly more diverse than mosquitoes, and our data suggest that mosquitoes filter out many bacteria, with Alphaproteobacteria in particular being far more abundant in water. These findings provide novel insight into the microbiome of mosquitoes in the region and provide a platform to improve our understanding of the fundamental mosquito-microbe interactions.

Anaesthetic-surgical guide in the treatment of ascending aorta and surgery of the ascending aorta and aortic arch. Consensus document of the Spanish Society of Cardiovascular and Endovascular Surgery and the Sociedad of Anaesthesiology, Resuscitation and Pain Therapy. / Guía anestésico-quirúrgica en el tratamiento de la cirugía de aorta ascendente y del arco aórtico. Documento de consenso de la Sociedad Española de Cirugía Cardiovascular y Endovascular y la Sociedad Española de Anestesiología, Reanimación y Terapeútica del Dolor.

Aortic pathology is always a challenge for the clinician, and must be diagnosed and treated by a multidisciplinary team due to the technical and technological complexity of the resources used. Ongoing efforts to implement a systematic, protocolized approach involving "Aortic teams" made up of cardiologists, cardiac surgeons, vascular surgeons, anaesthesiologists and radiologists, among others are now leading to improved outcomes. The aim of this consensus document drawn up by the Aortic working groups of the Spanish Society of Anaesthesiology, Resuscitation and Pain Therapy (SEDAR) and the Spanish Society of Thoracic and Cardiovascular Surgery (SECTCV) is to disseminate a set of working protocols. The latest consensus document of the European Association for Cardio-Thoracic Surgery (EACTS) and the European Society for Vascular Surgery (ESVS) define the concept of "AORTIC TEAM"(1). The aortic team should be closely involved from diagnosis to treatment and finally follow-up, and should be formed of cardiac and vascular surgeons working together with anaesthesiologists, cardiologists, radiologists and geneticists. Treatment of aortic pathologies should be centralised in large centres, because this is the only way to effectively understand the natural course of the disease, provide the entire range of treatment options under one umbrella and treat potential complications. A streamlined emergent care pathway (24/7 availability), adequate transportation and transfer capabilities, as well as rapid activation of the multidisciplinary team must be available. In light of the complexity and constant evolution of therapeutic options, we present this first version of the Anaesthesiology and surgical guidelines for surgery of the ascending aorta and aortic arch. Some questions will no doubt remain unanswered, and future versions will include new techniques that, though implemented in some centres, are still not widely recommended.

Efficacy and safety of rucaparib in previously treated, locally advanced or metastatic urothelial carcinoma from a phase 2, open-label trial (ATLAS).

BACKGROUND: ATLAS evaluated the efficacy and safety of the PARP inhibitor rucaparib in patients with previously treated locally advanced/unresectable or metastatic urothelial carcinoma (UC). METHODS: Patients with UC were enrolled independent of tumor homologous recombination deficiency (HRD) status and received rucaparib 600 mg BID. The primary endpoint was investigator-assessed objective response rate (RECIST v1.1) in the intent-to-treat and HRD-positive (loss of genome-wide heterozygosity ≥10%) populations. Key secondary endpoints were progression-free survival (PFS) and safety. Disease control rate (DCR) was defined post-hoc as the proportion of patients with a confirmed complete or partial response (PR), or stable disease lasting ≥16 weeks. RESULTS: Of 97 enrolled patients, 20 (20.6%) were HRD-positive, 30 (30.9%) HRD-negative, and 47 (48.5%) HRD-indeterminate. Among 95 evaluable patients, there were no confirmed responses. However, reductions in the sum of target lesions were observed, including 6 (6.3%) patients with unconfirmed PR. DCR was 11.6%; median PFS was 1.8 months (95% CI, 1.6-1.9). No relationship was observed between HRD status and efficacy endpoints. Median treatment duration was 1.8 months (range, 0.1-10.1). Most frequent any-grade treatment-emergent adverse events were asthenia/fatigue (57.7%), nausea (42.3%), and anemia (36.1%). Of 64 patients with data from tumor tissue samples, 10 (15.6%) had a deleterious alteration in a DNA damage repair pathway gene, including four with a deleterious BRCA1 or BRCA2 alteration. CONCLUSIONS: Rucaparib did not show significant activity in unselected patients with advanced UC regardless of HRD status. The safety profile was consistent with that observed in patients with ovarian or prostate cancer. TRIAL REGISTRATION: This trial was registered in ClinicalTrials.gov (NCT03397394). Date of registration: 12 January 2018. This trial was registered in EudraCT (2017-004166-10).

Atezolizumab in locally advanced or metastatic urothelial cancer: a pooled analysis from the Spanish patients of the IMvigor 210 cohort 2 and 211 studies

Background The studies IMvigor 210 cohort 2 and IMvigor211 evaluated the efficacy of atezolizumab in patients with locally advanced or metastatic urothelial cancer (mUC) upon progression to platinum-based chemotherapy worldwide. Yet, the real impact of this drug in specific geographical regions is unknown. Materials and methods We combined individual-level data from the 131 patients recruited in Spain from IMvigor210 cohort 2 and IMvigor211 in a pooled analysis. Efficacy and safety outcomes were assessed in the overall study population and according to PD-L1 expression on tumour-infiltrating immune cells. Results Full data were available for 127 patients; 74 (58%) received atezolizumab and 53 (42%) chemotherapy. Atezolizumab patients had a numerically superior median overall survival although not reaching statistical significance (9.2 months vs 7.7 months). No statistically significant differences between arms were observed in overall response rates (20.3% vs 37.0%) or progression-free survival (2.1 months vs 5.3 months). Nonetheless, median duration of response was superior for the immunotherapy arm (non-reached vs 6.4 months; p = 0.005). Additionally, among the responders, the 12-month survival rates seemed to favour atezolizumab (66.7% vs 19.9%). When efficacy was analyzed based on PD-L1 expression status, no significant differences were found. Treatment-related adverse events of any grade occurred more frequently in the chemotherapy arm [46/57 (81%) vs 44/74 (59%)]. Conclusion Patients who achieved an objective response on atezolizumab presented a longer median duration of response and numerically superior 12 month survival rates when compared with chemotherapy responders along with a more favorable safety profile. PD-L1 expression did not discriminate patients who might benefit from atezolizumab (AU)

RETRACTED: Anesthesic and surgical guideline for the treatment of the thoraco-abdominal aorta. Consensus Document of the Spanish Societies of Anesthesia and Cardiovascular Surgery. / Guía anestésico-quirúrgica en el tratamiento de la patología de aorta toracoabdominal. Documento de Consenso de la Sociedad Española de Cirugía Cardiovascular Endovascular y la Sociedad Española de Anestesiología, Reanimación y Terapeútica del Dolor.

Este artículo ha sido retirado por indicación del Editor Jefe de la revista, después de constatar que parte de su contenido había sido plagiado, sin mencionar la fuente original: European Heart Journal (2014) 35, 2873 926.: https://academic.oup.com/eurheartj/article/35/41/2873/407693#89325738 El autor de correspondencia ha sido informado de la decisión y está de acuerdo con la retirada del artículo. El Comité Editorial lamenta las molestias que esta decisión pueda ocasionar. Puede consultar la política de Elsevier sobre la retirada de artículos en https://www.elsevier.com/about/our-business/policies/article-withdrawal

Atezolizumab in locally advanced or metastatic urothelial cancer: a pooled analysis from the Spanish patients of the IMvigor 210 cohort 2 and 211 studies.

BACKGROUND: The studies IMvigor 210 cohort 2 and IMvigor211 evaluated the efficacy of atezolizumab in patients with locally advanced or metastatic urothelial cancer (mUC) upon progression to platinum-based chemotherapy worldwide. Yet, the real impact of this drug in specific geographical regions is unknown. MATERIALS AND METHODS: We combined individual-level data from the 131 patients recruited in Spain from IMvigor210 cohort 2 and IMvigor211 in a pooled analysis. Efficacy and safety outcomes were assessed in the overall study population and according to PD-L1 expression on tumour-infiltrating immune cells. RESULTS: Full data were available for 127 patients; 74 (58%) received atezolizumab and 53 (42%) chemotherapy. Atezolizumab patients had a numerically superior median overall survival although not reaching statistical significance (9.2 months vs 7.7 months). No statistically significant differences between arms were observed in overall response rates (20.3% vs 37.0%) or progression-free survival (2.1 months vs 5.3 months). Nonetheless, median duration of response was superior for the immunotherapy arm (non-reached vs 6.4 months; p = 0.005). Additionally, among the responders, the 12-month survival rates seemed to favour atezolizumab (66.7% vs 19.9%). When efficacy was analyzed based on PD-L1 expression status, no significant differences were found. Treatment-related adverse events of any grade occurred more frequently in the chemotherapy arm [46/57 (81%) vs 44/74 (59%)]. CONCLUSION: Patients who achieved an objective response on atezolizumab presented a longer median duration of response and numerically superior 12 month survival rates when compared with chemotherapy responders along with a more favorable safety profile. PD-L1 expression did not discriminate patients who might benefit from atezolizumab.

A 70% Reduction in Mosquito Populations Does Not Require Removal of 70% of Mosquitoes.

We added a vector control component to our existing abundance model to simulate intensive vector control in Puerto Rico. Removing 20-30% of gravid females in the model matches observed 60-80% reductions. The model's capacity to reproduce vector control increases its utility for planning and evaluation strategies.

Unusual winter Saharan dust intrusions at Northwest Spain: Air quality, radiative and health impacts.

Saharan air masses can transport high amounts of mineral dust particles and biological material to the Iberian Peninsula. During winter, this kind of events is not very frequent and usually does not reach the northwest of the Peninsula. However, between 21 and 22 February 2016 and between 22 and 23 February 2017, two exceptional events were registered in León (Spain), which severely affected air quality. An integrative approach including: i) typical synoptic conditions; ii) aerosol chemical composition; iii) particle size distributions; iv) pollen concentration; v) aerosol optical depth (AOD); vi) radiative forcing and vii) estimation of the impact of aerosols in the respiratory tract, was carried out. In the global characterization of these events, the exceedance of the PM10 daily limit value, an increase in the coarse mode and a rise in the iron concentration were observed. On the 2016 event, an AOD and extinction-related Ångström exponent clearly characteristic of desert aerosol (1.1 and 0.05, respectively) were registered. Furthermore, pollen grains not typical of flowering plants in this period were identified. The chemical analysis of the aerosol from the 2017 event allowed us to confirm the presence of the main elements associated with mineral sources (aluminum, calcium, and silica concentrations). An increase in the SO42-, NO3- and Cl- concentrations during the Saharan dust intrusion was also noted. However, in this event, there was no presence of atypical pollen types. The estimated dust radiative forcing traduced a cooling effect for surface and atmosphere during both events, corroborated by trends of radiative flux measurements. The estimated impact on the respiratory tract regions of the high levels of particulate matter during both Saharan dust intrusions showed high levels for the respirable fraction.

SEOM clinical guideline for treatment of muscle-invasive and metastatic urothelial bladder cancer (2018)

The goal of this article is to provide recommendations about the management of muscle-invasive (MIBC) and metastatic bladder cancer. New molecular subtypes of MIBC are associated with specific clinical-pathological characteristics. Radical cystectomy and lymph node dissection are the gold standard for treatment and neoadjuvant chemotherapy with a cisplatin-based combination should be recommended in fit patients. The role of adjuvant chemotherapy in MIBC remains controversial; its use must be considered in patients with high-risk who are able to tolerate a cisplatin-based regimen, and have not received neoadjuvant chemotherapy. Bladder-preserving approaches are reasonable alternatives to cystectomy in selected patients for whom cystectomy is not contemplated either for clinical or personal reasons. Cisplatin-based combination chemotherapy is the standard first-line protocol for metastatic disease. In the case of unfit patients, carboplatin-gemcitabine should be considered the preferred first-line chemotherapy treatment option, while pembrolizumab and atezolizumab can be contemplated for individuals with high PD-L1 expression. In cases of progression after platinum-based therapy, PD-1/PD-L1 inhibitors are standard alternatives. Vinflunine is another option when anti-PD-1/PD-L1 therapy is not possible. There are no data from randomized clinical trials regarding moving on to immuno-oncology agents

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SEOM clinical guideline for treatment of muscle-invasive and metastatic urothelial bladder cancer (2018).

The goal of this article is to provide recommendations about the management of muscle-invasive (MIBC) and metastatic bladder cancer. New molecular subtypes of MIBC are associated with specific clinical-pathological characteristics. Radical cystectomy and lymph node dissection are the gold standard for treatment and neoadjuvant chemotherapy with a cisplatin-based combination should be recommended in fit patients. The role of adjuvant chemotherapy in MIBC remains controversial; its use must be considered in patients with high-risk who are able to tolerate a cisplatin-based regimen, and have not received neoadjuvant chemotherapy. Bladder-preserving approaches are reasonable alternatives to cystectomy in selected patients for whom cystectomy is not contemplated either for clinical or personal reasons. Cisplatin-based combination chemotherapy is the standard first-line protocol for metastatic disease. In the case of unfit patients, carboplatin-gemcitabine should be considered the preferred first-line chemotherapy treatment option, while pembrolizumab and atezolizumab can be contemplated for individuals with high PD-L1 expression. In cases of progression after platinum-based therapy, PD-1/PD-L1 inhibitors are standard alternatives. Vinflunine is another option when anti-PD-1/PD-L1 therapy is not possible. There are no data from randomized clinical trials regarding moving on to immuno-oncology agents.

A comparison of mosquito densities, weather and infection rates of Aedes aegypti during the first epidemics of Chikungunya (2014) and Zika (2016) in areas with and without vector control in Puerto Rico.

In Puerto Rico, the first records of the transmission of Chikungunya (CHIKV) and Zika (ZIKV) viruses were confirmed in May 2014 and December 2015, respectively. Transmission of CHIKV peaked in September 2014, whereas that of ZIKV peaked in August 2016. The emergence of these mosquito-transmitted arboviruses in the context of a lack of human population immunity allowed observations of whether the outbreaks were associated with Aedes aegypti (Diptera: Culicidae) densities and weather. Mosquito density was monitored weekly in four communities using sentinel autocidal gravid ovitraps (AGO traps) during 2016 in order to provide data to be compared with the findings of a previous study carried out during the 2014 CHIKV epidemic. Findings in two communities protected against Ae. aegypti using mass AGO trapping (three traps per house in most houses) were compared with those in two nearby communities without vector control. Mosquito pools were collected to detect viral RNA of ZIKV, CHIKV and dengue virus. In areas without vector control, mosquito densities and rates of ZIKV detection in 2016 were significantly higher, similarly to those observed for CHIKV in 2014. The density of Ae. aegypti in treated sites was less than two females/trap/week, which is similar to the putative adult female threshold for CHIKV transmission. No significant differences in mosquito density or infection rates with ZIKV and CHIKV at the same sites between years were observed. Although 2016 was significantly wetter, mosquito densities were similar.

PDGF-BB regulates splitting angiogenesis in skeletal muscle by limiting VEGF-induced endothelial proliferation.

VEGF induces normal or aberrant angiogenesis depending on its dose in the microenvironment around each producing cell in vivo. This transition depends on the balance between VEGF-induced endothelial stimulation and PDGF-BB-mediated pericyte recruitment, and co-expression of PDGF-BB normalizes aberrant angiogenesis despite high VEGF doses. We recently found that VEGF over-expression induces angiogenesis in skeletal muscle through an initial circumferential vascular enlargement followed by longitudinal splitting, rather than sprouting. Here we investigated the cellular mechanism by which PDGF-BB co-expression normalizes VEGF-induced aberrant angiogenesis. Monoclonal populations of transduced myoblasts, expressing similarly high levels of VEGF alone or with PDGF-BB, were implanted in mouse skeletal muscles. PDGF-BB co-expression did not promote sprouting and angiogenesis that occurred through vascular enlargement and splitting. However, enlargements were significantly smaller in diameter, due to a significant reduction in endothelial proliferation, and retained pericytes, which were otherwise lost with high VEGF alone. A time-course of histological analyses and repetitive intravital imaging showed that PDGF-BB co-expression anticipated the initiation of vascular enlargement and markedly accelerated the splitting process. Interestingly, quantification during in vivo imaging suggested that a global reduction in shear stress favored the initiation of transluminal pillar formation during VEGF-induced splitting angiogenesis. Quantification of target gene expression showed that VEGF-R2 signaling output was significantly reduced by PDGF-BB co-expression compared to VEGF alone. In conclusion, PDGF-BB co-expression prevents VEGF-induced aberrant angiogenesis by modulating VEGF-R2 signaling and endothelial proliferation, thereby limiting the degree of circumferential enlargement and enabling efficient completion of vascular splitting into normal capillary networks despite high VEGF doses.

Effects of Oral Prednisone Administration on Serum Cystatin C in Dogs.

BACKGROUND: Oral administration of glucocorticoid alters serum cystatin C (sCysC) concentration in humans. OBJECTIVE: To determine if oral administration of prednisone alters sCysC in dogs without pre-existing renal disease. ANIMALS: Forty six dogs were included: 10 dogs diagnosed with steroid responsive meningitis arteritis (SRMA; group A), 20 dogs diagnosed of pituitary-dependent hyperadrenocorticism (PDH; group B), and 16 healthy control dogs (group C). METHODS: Retrospective observational study. SRMA diagnosed dogs were administered prednisone 4 mg/kg/24 h PO 7 days, reducing the dose to 2 mg/kg/24 h 7 days before medication withdrawal. In group A, sampling was performed at days 0, 7, 14 and a final control at day 21. Blood and urine samples were collected in the 3 groups, and in group A, sampling was performed at all time points (days 1, 7, 14, and 21). RESULTS: In group A, sCysC was significantly higher at day 7 compared to the control group (0.4 ± 0.04 mg/L vs. 0.18 ± 0.03 mg/L mean ± SEM respectively P < 0.01); sCysC values decreased to basal at day 14 when the dose was decreased and after 1 week of withdrawal of prednisone (0.27 ± 0.03 mg/L for group A at day 14 and 0.15 ± 0.02 mg/L at day 21; P > 0.05). Dogs with PDH included in group B did not have significant differences in sCysC (0.22 ± 0.03 mg/L) compared to control (P > 0.05). CONCLUSIONS AND CLINICAL IMPORTANCE: Oral administration of prednisone unlike altered endogenous glucocorticoid production, increases sCysC in dogs in a dose-dependent fashion.

A randomized phase II/III study of cabazitaxel versus vinflunine in metastatic or locally advanced transitional cell carcinoma of the urothelium (SECAVIN).

BACKGROUND: Despite the advent of immunotherapy in urothelial cancer, there is still a need to find effective cytotoxic agents beyond first and second lines. Vinflunine is the only treatment approved in this setting by the European Medicines Agency and taxanes are also widely used in second line. Cabazitaxel is a taxane with activity in docetaxel-refractory cancers. A randomized study was conducted to compare its efficacy versus vinflunine. PATIENTS AND METHODS: This is a multicenter, randomized, open-label, phase II/III study, following a Simon's optimal method with stopping rules based on an interim futility analysis and a formal efficacy analysis at the end of the phase II. ECOG Performance Status, anaemia and liver metastases were stratification factors. Primary objectives were overall response rate for the phase II and overall survival for the phase III. RESULTS: Seventy patients were included in the phase II across 19 institutions in Europe. Baseline characteristics were well balanced between the two arms. Three patients (13%) obtained a partial response on cabazitaxel (95% CI 2.7-32.4) and six patients (30%) in the vinflunine arm (95% CI 11.9-54.3). Median progression-free survival for cabazitaxel was 1.9 versus 2.9 months for vinflunine (P = 0.039). The study did not proceed to phase III since the futility analysis showed a lack of efficacy of cabazitaxel. A trend for overall survival benefit was found favouring vinflunine (median 7.6 versus 5.5 months). Grade 3- to 4-related adverse events were seen in 41% patients with no difference between the two arms. CONCLUSION: This phase II/III second line bladder study comparing cabazitaxel with vinflunine was closed when the phase II showed a lack of efficacy of the cabazitaxel arm. Vinflunine results were consistent with those known previously. TRIAL NUMBER: NCT01830231.

Clorpromazina retrobulbar en el manejo del ojo doloroso ciego o con baja visión / Retrobulbar chlorpromazine in management of painful eye in blind or low vision patients

OBJETIVO: Evaluar los resultados de la aplicación de clorpromazina retrobulbar en el manejo del ojo doloroso ciego o con muy mala visión. MÉTODOS: Se realizó una revisión descriptiva retrospectiva de las historias clínicas de 33 pacientes que fueron tratados con inyección retrobulbar de clorpromazina (25mg) en el Centro Oftalmológico Virgilio Galvis. RESULTADOS: Se logró un control del dolor en el 90% de los casos (con un seguimiento promedio de 2,1 años). La presión intraocular promedio disminuyó en un 37%. En 7 de los 12 ojos que mantenían visión residual se perdió algún grado en la visión. Un paciente requirió un procedimiento ciclodestructivo adicional; otro, una inyección de alcohol absoluto y otro terminó en evisceración para lograr el control del dolor. No se presentaron complicaciones serias con la terapia. CONCLUSIONES: El empleo de la inyección de clorpromazina retrobulbar es una opción válida en casos de ojos dolorosos, con mal pronóstico visuaL

OBJECTIVE: To evaluate the results of applying retrobulbar chlorpromazine in the management of patients with painful blind eyes or with very poor vision. METHODS: A retrospective, descriptive review was carried out on the medical records of 33 patients who were treated with a retrobulbar injection of chlorpromazine (25mg) for the management of painful blind eyes in Centro Oftalmológico Virgilio Galvis. RESULTS: Pain control was achieved in 90% of cases (with mean follow-up of 2.1 years). The mean intraocular pressure decreased by 37%. In 7 out of 12 eyes that maintained residual vision, loss of some degree of vision was acknowledged. One patient required an additional cyclodestructive procedure, another one required an absolute alcohol injection, and in an additional case evisceration surgery was necessary to achieve pain control. No serious complications were noted with this therapy. CONCLUSIONS: Retrobulbar injection of chlorpromazine is a valid option in painful, blind eye cases (or with very poor vision) with a poor visual prognosis

Retrobulbar chlorpromazine in management of painful eye in blind or low vision patients. / Clorpromazina retrobulbar en el manejo del ojo doloroso ciego o con baja visión.

OBJECTIVE: To evaluate the results of applying retrobulbar chlorpromazine in the management of patients with painful blind eyes or with very poor vision. METHODS: A retrospective, descriptive review was carried out on the medical records of 33 patients who were treated with a retrobulbar injection of chlorpromazine (25mg) for the management of painful blind eyes in Centro Oftalmológico Virgilio Galvis. RESULTS: Pain control was achieved in 90% of cases (with mean follow-up of 2.1 years). The mean intraocular pressure decreased by 37%. In 7 out of 12 eyes that maintained residual vision, loss of some degree of vision was acknowledged. One patient required an additional cyclodestructive procedure, another one required an absolute alcohol injection, and in an additional case evisceration surgery was necessary to achieve pain control. No serious complications were noted with this therapy. CONCLUSIONS: Retrobulbar injection of chlorpromazine is a valid option in painful, blind eye cases (or with very poor vision) with a poor visual prognosis.