Determination of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and systemic immune-inflammation index in dogs with leptospirosis.

Leptospirosis is a globally distributed zoonosis with multisystemic involvement in canine species, capable of causing a pulmonary hemorrhagic syndrome (LPHS) in the most severe cases. In humans, the neutrophil to lymphocyte ratio (NLR), platelets to lymphocytes (PLR) and systemic immune-inflammation index (SII) have been described as predictors of morbidity and mortality in various pathologies, but no such studies have been developed for canine leptospirosis. Hence, we aimed to assess the usefulness of NLR, PLR and SII in dogs affected with leptospirosis, focusing on those that died or survived after hospitalization, whether or not they developed LPHS. The leptospirosis group was composed by 36 dogs while the control group consisted of 32 healthy dogs. The NLR, associated with inflammation, demonstrated a threefold or greater increase in all leptospirosis groups compared to the control group (median 2.44 ± 1.66) (developing or not LPHS). Dogs that died (median 67.78 ± 158.67), developed LHPS (median 85.17 ± 143.77), or both developed LHPS and died (median 67.78 ± 155,14) had a lower PLR in comparison to the control group (median 101,82 ± 53,75) and the rest of groups, but no statistically significant differences were observed (p > 0.05). The SII was higher in leptospirosis-affected dogs that survived (median 1356,92 ± 2726,29) and statistically significant differences were observed in those who did not develop LPHS (median 1770,41 ± 2630,77; p < 0.05) compared to the control group (median 555,21 ± 313,26). Our data shows that NLR may be used as inflammation indicator, while more studies are needed for PLR and SII in canine leptospirosis.

First-line therapy with palbociclib in patients with advanced HR+/HER2- breast cancer: The real-life study PALBOSPAIN.

PURPOSE: To evaluate the efficacy and safety of first-line therapy with palbociclib in a Spanish cohort treated after palbociclib approval. METHODS: PALBOSPAIN is an observational, retrospective, multicenter study evaluating real-world patterns and outcomes with 1 L palbociclib in men and women (any menopausal status) with advanced HR+/HER2- BC diagnosed between November 2017 and November 2019. The primary endpoint was real-world progression-free survival (rw-PFS). Secondary endpoints included overall survival (OS), the real-world response rate (rw-RR), the clinical benefit rate, palbociclib dose reduction, and safety. RESULTS: A total of 762 patients were included. The median rw-PFS and OS were 24 months (95% CI 21-27) and 42 months (40-not estimable [NE]) in the whole population, respectively. By cohort, the median rw-PFS and OS were as follows: 28 (95% CI 23-39) and 44 (95% CI 38-NE) months in patients with de novo metastatic disease, 13 (95% CI 11-17) and 36 months (95% CI 31-41) in patients who experienced relapse < 12 months after the end of ET, and 31 months (95% CI 26-37) and not reached (NR) in patients who experienced relapse > 12 months after the end of ET. rw-PFS and OS were longer in patients with oligometastasis and only one metastatic site and those with non-visceral disease. The most frequent hematologic toxicity was neutropenia (72%; grade ≥ 3: 52.5%), and the most common non-hematologic adverse event was asthenia (38%). CONCLUSION: These findings, consistent with those from clinical trials, support use of palbociclib plus ET as 1 L for advanced BC in the real-world setting, including pre-menopausal women and men. TRIAL REGISTRATION NUMBER: NCT04874025 (PALBOSPAIN). Date of registration: 04/30/2021 retrospectively registered.

Clinical importance of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and systemic immune-inflammation index in dogs with leishmaniasis.

Leishmaniasis is a zoonotic disease caused by Leishmania spp., impacts multiple systems and organs. While hematological and biochemical profiles aren't definitive for diagnosis, recent studies have identified the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) as predictors of morbidity and mortality in critically ill human and dog patients. This study examined 100 dogs diagnosed with leishmaniasis, categorized by the International Renal Interest Society (IRIS) stages 1-4. Additionally, the dogs were divided based on whether they survived less or more than one year (L1Y and G1Y). Control group consisted of 43 dogs. The NLR increased as the disease progressed (IRIS 1-4), presenting statistically significant differences (P<0.05) when compared to the control group (2,37±2,08) IRIS 3 and 4 (4,59±13,39 and 6,99±12,86, respectively), and G1Y and L1Y (3,60±4,02 and 4,87±5,82, respectively). Significant changes in SII were only evident in short-term survivors (L1Y 951,93±1402) and advanced renal disease cases (IRIS 4 stage 1073,68±1901,09). Conversely, PLR remained largely unchanged. In conclusion, these results suggest that the neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) may serve as potential markers for assessing disease progression and prognosis in dogs diagnosed with leishmaniasis.

Factors influencing initial implementation of an online community-based exercise intervention with adults living with HIV: a systems approach.

Introduction: Online community-based exercise (CBE) is a digital health intervention and rehabilitation strategy that promotes health among people living with HIV. Our aim was to describe the factors influencing initial implementation of a pilot online CBE intervention with adults living with HIV using a systems approach, as recommended by implementation science specialists. Methods: We piloted the implementation of a 6-month online CBE intervention and 6-month independent exercise follow up, in partnership with the YMCA in Toronto, Canada. We recruited adults living with HIV who identified themselves as safe to engage in exercise. The intervention phase included personalized exercise sessions online with a personal trainer; exercise equipment; access to online exercise classes; and a wireless physical activity monitor. Two researchers documented implementation factors articulated by participants and the implementation team during early implementation, defined as recruitment, screening, equipment distribution, technology orientation, and baseline assessments. Data sources included communication with participants; daily team communication; weekly team discussions; and in-person meetings. We documented implementation factors in meeting minutes, recruitment screening notes, and email communication; and analyzed the data using a qualitative descriptive approach using a systems engineering method called Cognitive Work Analysis. Results: Thirty-three adults living with HIV enrolled in the study (n = 33; median age: 52 years; cis-men: 22, cis-women: 10, non-binary: 1). Fifty-five factors influencing implementation, spanned five layers: (i) Natural, including weather and the COVID-19 virus; (ii) Societal, including COVID-19 impacts (e.g. public transit health risks impacting equipment pick-ups); (iii) Organizational, including information dissemination (e.g. tech support) and logistics (e.g. scheduling); (iv) Personal, including physical setting (e.g. space) and digital setting (e.g. device access); and (v) Human, including health (e.g. episodic illness) and disposition (e.g. motivation). The implementation team experienced heightened needs to respond rapidly; sustain engagement; and provide training and support. Additional organizational factors included a committed fitness training and research team with skills spanning administration and logistics, participant engagement, technology training, physical therapy, and research ethics. Conclusion: Fifty-five factors spanning multiple layers illustrate the complexities of online CBE with adults living with HIV. Initial implementation required a dedicated, rehabilitation-centred, multi-skilled, multi-stakeholder team to address a diverse set of factors.

Paleomagnetic techniques can date speleothems with high concentrations of detrital material.

The U-series dating of young and 'dirty' speleothems is challenging due to difficulties in assessing the isotopic composition of detrital contaminants and the low-abundance of 230Th generated in situ. Here we propose a new dating approach based on the comparison of a speleothem's paleomagnetic directions to reference curves from global paleomagnetic reconstructions. This approach is demonstrated on a stalagmite collected from the Soprador do Carvalho cave in the Central Region of Portugal. A radioisotopic age model, built using four U-series ages and three 14C, suggests relatively steady carbonate precipitation from ~ 5760 BCE until ~ 1920 CE. Forty-five 6 mm-thick subsamples were analyzed using alternating field and thermal demagnetization protocols, providing well-defined, primary magnetic directions. An age model of the stalagmite was obtained by fitting its paleomagnetic record with the reference paleosecular variation curves obtained by previous paleo-reconstruction models, applying statistical bootstrapping analysis to define their best fit. The resulting age models fit closely with the radioisotopic age model but provide a significantly higher time resolution. We reach the same conclusion when applying this approach to another stalagmite from the Algarve region of Portugal. Our approach thus appears a promising alternative to date young speleothems with high detrital contents.

Colágeno polivinilpirrolidona versus mitomicina C en trabeculectomía en pacientes con glaucoma primario de ángulo abierto. Seguimiento a 36 meses / Outcomes of trabeculectomy with polyvinylpyrrolidone collagen versus mitomycin in primary open angle glaucoma. 36-month follow-up

Propósito Describir y comparar los efectos de la aplicación intraoperatoria de colágeno polivinilpirrolidona (PVP) versus mitomicina C (MMC) en el patrón de cambio de la presión intraocular (PIO) y del número de medicamentos hipotensores utilizados en un seguimiento a 36 meses en pacientes con glaucoma primario de ángulo abierto (GPAA) operados de trabeculectomía. Métodos Estudio prospectivo, comparativo y aleatorizado. Veintiséis ojos de 26 pacientes con diagnóstico de GPAA, sin cirugías incisionales de glaucoma previas, fueron operados de trabeculectomía y aleatorizados a recibir PVP o MMC durante el procedimiento. Todos los pacientes cumplieron un seguimiento de 36 meses. Los resultados principales medidos fueron cambios en la PIO y el número de medicamentos hipotensores durante el seguimiento. Resultados El análisis multivariado reveló que la reducción de la PIO media del preoperatorio a los 36 meses de seguimiento fue de 7,62mmHg (3,05; 12,18) en el grupo de MMC y de 8,15mmHg (−0,64; 16,95) en el grupo de la PVP. La reducción media porcentual de la PIO fue del 37,09% (15,93; 58,17) en el grupo de MMC y del 36,08% (5,16; 67,20) en el grupo de la PVP. El cambio en el número de medicamentos del preoperatorio a los 36 meses de seguimiento fue de −0,92 medicamentos (-2,38; +1,54) para el grupo de MMC y de −1 medicamentos (−3,12, +1,12) para el grupo de la PVP. Ambos grupos tuvieron una disminución estadísticamente significativa de la PIO durante el seguimiento (p<0,001), pero no hubo una diferencia discernible entre los grupos (p=0,5975). El análisis de sensibilidad mostró que un modelo de tendencia lineal es adecuado para describir la reducción de la PIO durante el seguimiento. Ambos grupos tuvieron una reducción estadísticamente significativa de medicamentos del preoperatorio al final del seguimiento (p<0,05), tampoco hubo una diferencia discernible entre los grupos (p=0,2917)(AU)

Purpose Describe and compare the effects of intraoperative application of Polyvinylpyrrolidone Collagen (PVP) versus Mitomycin C (MMC) on the pattern of change in mean IOP reduction and mean number of medications over 36-months follow-up in patients with primary open angle glaucoma (POAG) undergoing trabeculectomy. Methods Prospective, randomized, comparative study. Twenty-six eyes of 26 patients with POAG and no previous incisional glaucoma surgery underwent trabeculectomy and were randomized to PVP or MMC and completed a 36-month follow-up. Main outcome measures were IOP and number of glaucoma medications. Multivariate longitudinal analysis was performed by fitting a linear trend model adjusting for baseline response for the IOP outcome and a log-linear regression model with within-subject associations for the number of hypotensive medications outcome. Sensitivity analysis was performed to assess lower and higher order polynomial trends over time in IOP. Results The univariate analysis revealed that the mean IOP reduction from baseline to 36 months was 7.62mmHg (3.05; 12.18) in the MMC group and 8.15mmHg (−0.64; 16.95) in the PVP group. Mean percentage IOP reduction from baseline was 37.09% (15.93; 58.17) and 36.08% (5.16; 67.20) in the PVP group. Mean change in number of medications from baseline to 36 months was −0.92 medications (−3.38; +1.54) for the MMC group and −1 medication (−3.12; +1.12) for the PVP group. Both groups had a statistically significant decline in mean IOP over the follow-up period (p<0.001) but there was no discernible difference between the two exposure groups in the rate of change in IOP (p=0.5975). Sensitivity analysis showed that a linear trend model is adequate to describe the IOP reduction over the follow-up period. Both groups had a statistically significant change in the number of hypotensive medications used between baseline and month 36 (p<0.05) but there was no discernible difference between exposure groups (p=0.2917) (AU)

Outcomes of trabeculectomy with polyvinylpyrrolidone collagen versus mitomycin in primary open angle glaucoma. 36-month follow-up. / Colágeno polivinilpirrolidona versus mitomicina C en trabeculectomía en pacientes con glaucoma primario de ángulo abierto. Seguimiento a 36 meses.

PURPOSE: Describe and compare the effects of intraoperative application of Polyvinylpyrrolidone Collagen (PVP) versus Mitomycin C (MMC) on the pattern of change in mean IOP reduction and mean number of medications over 36-months follow-up in patients with primary open angle glaucoma (POAG) undergoing trabeculectomy. METHODS: Prospective, randomized, comparative study. Twenty-six eyes of 26 patients with POAG and no previous incisional glaucoma surgery underwent trabeculectomy and were randomized to PVP or MMC and completed a 36-month follow-up. Main outcome measures were IOP and number of glaucoma medications. Multivariate longitudinal analysis was performed by fitting a linear trend model adjusting for baseline response for the IOP outcome and a log-linear regression model with within-subject associations for the number of hypotensive medications outcome. Sensitivity analysis was performed to assess lower and higher order polynomial trends over time in IOP. RESULTS: The univariate analysis revealed that the mean IOP reduction from baseline to 36 months was 7.62mmHg (3.05; 12.18) in the MMC group and 8.15mmHg (-0.64; 16.95) in the PVP group. Mean percentage IOP reduction from baseline was 37.09% (15.93; 58.17) and 36.08% (5.16; 67.20) in the PVP group. Mean change in number of medications from baseline to 36 months was -0.92 medications (-3.38; +1.54) for the MMC group and -1 medication (-3.12; +1.12) for the PVP group. Both groups had a statistically significant decline in mean IOP over the follow-up period (p<0.001) but there was no discernible difference between the two exposure groups in the rate of change in IOP (p=0.5975). Sensitivity analysis showed that a linear trend model is adequate to describe the IOP reduction over the follow-up period. Both groups had a statistically significant change in the number of hypotensive medications used between baseline and month 36 (p<0.05) but there was no discernible difference between exposure groups (p=0.2917). Both the PVP and MMC groups showed an initial reduction in number of medications until month 12 and a relatively linear increase towards month 36. A longer follow-up may be warranted to reveal differences in the number of medications between the two exposure groups. Postoperative complications were less frequent in the PVP group. CONCLUSIONS: The use of PVP during trabeculectomy achieves and maintains a statistically significant IOP reduction from baseline to 36 months and decreases the number of glaucoma medications. Secondary outcome measures showed a lower incidence of adverse events in the PVP group.

Coupling air temperature records and gravimetric data to interpret ventilation patterns in a Mediterranean karstic system (Nerja-Pintada caves, southern Spain).

Microclimate and geophysical studies are commonly applied to the characterization of karst systems although they are usually used separately. The main purpose of this manuscript is to show how the analysis of the data from both these research methods is a useful tool in the characterization of karst systems and we present the analysis of a specific case study: the Nerja- Pintada caves system. The joint analysis of the Nerja Cave and external air data (mainly temperatures) and the pre-existing gravimetric data of its surroundings (residual gravity anomaly map) have allowed us: 1) to postulate the existence of an unknown great cavity located near to the Nerja Cave and with direct influence in its ventilation and 2) to propose a new model of the Nerja-Pintada caves ventilation based on the changing connection between a "main cavity" system (Nerja Cave), with basically a transmissive function of airflows and an "annex cavities" sub-system, with different functioning as far as the airflow is concerned: transmissive in the case of Pintada Cave and capacitive in the case of the geophysically-located cave.

Targeted next-generation sequencing of circulating-tumor DNA for tracking minimal residual disease in localized colon cancer.

BACKGROUND: A high percentage of patients diagnosed with localized colon cancer (CC) will relapse after curative treatment. Although pathological staging currently guides our treatment decisions, there are no biomarkers determining minimal residual disease (MRD) and patients are at risk of being undertreated or even overtreated with chemotherapy in this setting. Circulating-tumor DNA (ctDNA) can to be a useful tool to better detect risk of relapse. PATIENTS AND METHODS: One hundred and fifty patients diagnosed with localized CC were prospectively enrolled in our study. Tumor tissue from those patients was sequenced by a custom-targeted next-generation sequencing (NGS) panel to characterize somatic mutations. A minimum variant allele frequency (VAF) of 5% was applied for variant filtering. Orthogonal droplet digital PCR (ddPCR) validation was carried out. We selected known variants with higher VAF to track ctDNA in the plasma samples by ddPCR. RESULTS: NGS found known pathological mutations in 132 (88%) primary tumors. ddPCR showed high concordance with NGS (r = 0.77) for VAF in primary tumors. Detection of ctDNA after surgery and in serial plasma samples during follow-up were associated with poorer disease-free survival (DFS) [hazard ratio (HR), 17.56; log-rank P = 0.0014 and HR, 11.33; log-rank P = 0.0001, respectively]. Tracking at least two variants in plasma increased the ability to identify MRD to 87.5%. ctDNA was the only significantly independent predictor of DFS in multivariable analysis. In patients treated with adjuvant chemotherapy, presence of ctDNA after therapy was associated with early relapse (HR 10.02; log-rank P < 0.0001). Detection of ctDNA at follow-up preceded radiological recurrence with a median lead time of 11.5 months. CONCLUSIONS: Plasma postoperative ctDNA detected MRD and identified patients at high risk of relapse in localized CC. Mutation tracking with more than one variant in serial plasma samples improved our accuracy in predicting MRD.

Author Correction: Multi-centennial fluctuations of radionuclide production rates are modulated by the Earth's magnetic field.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Precursory worldwide signatures of earthquake occurrences on Swarm satellite data.

The study of the preparation phase of large earthquakes is essential to understand the physical processes involved, and potentially useful also to develop a future reliable short-term warning system. Here we analyse electron density and magnetic field data measured by Swarm three-satellite constellation for 4.7 years, to look for possible in-situ ionospheric precursors of large earthquakes to study the interactions between the lithosphere and the above atmosphere and ionosphere, in what is called the Lithosphere-Atmosphere-Ionosphere Coupling (LAIC). We define these anomalies statistically in the whole space-time interval of interest and use a Worldwide Statistical Correlation (WSC) analysis through a superposed epoch approach to study the possible relation with the earthquakes. We find some clear concentrations of electron density and magnetic anomalies from more than two months to some days before the earthquake occurrences. Such anomaly clustering is, in general, statistically significant with respect to homogeneous random simulations, supporting a LAIC during the preparation phase of earthquakes. By investigating different earthquake magnitude ranges, not only do we confirm the well-known Rikitake empirical law between ionospheric anomaly precursor time and earthquake magnitude, but we also give more reliability to the seismic source origin for many of the identified anomalies.

New horizons in breast cancer: the promise of immunotherapy.

Immunology and immunotherapy of cancer is an expanding field in oncology, with recent great achievements obtained through the new successful approaches implemented to circumvent immune evasion, which is undoubtedly considered a novel hallmark of cancer. Translational research in this topic has revealed targets that can be modulated in the clinical setting with new compounds and strategies. Like most of the tumors, breast cancer is considered a complex and heterogeneous disease in which host immune responses have been also recently demonstrated of critical relevance. T infiltrating lymphocyte measurement is suggested as a powerful new tool necessary to predict early breast cancer evolution, especially for the her2-positive and triple-negative subtypes. Other biomarkers in tissue and peripheral blood are under intense scrutiny to ascertain their eventual role as prognostic and/or predictive factors. This background has fueled the interest in developing clinical research strategies to test activity of modern immunotherapy in breast cancer, which constitutes the main focus of this review.

New perspectives in the study of the Earth's magnetic field and climate connection: The use of transfer entropy.

The debated question on the possible relation between the Earth's magnetic field and climate has been usually focused on direct correlations between different time series representing both systems. However, the physical mechanism able to potentially explain this connection is still an open issue. Finding hints about how this connection could work would suppose an important advance in the search of an adequate physical mechanism. Here, we propose an innovative information-theoretic tool, i.e. the transfer entropy, as a good candidate for this scope because is able to determine, not simply the possible existence of a connection, but even the direction in which the link is produced. We have applied this new methodology to two real time series, the South Atlantic Anomaly (SAA) area extent at the Earth's surface (representing the geomagnetic field system) and the Global Sea Level (GSL) rise (for the climate system) for the last 300 years, to measure the possible information flow and sense between them. This connection was previously suggested considering only the long-term trend while now we study this possibility also in shorter scales. The new results seem to support this hypothesis, with more information transferred from the SAA to the GSL time series, with about 90% of confidence level. This result provides new clues on the existence of a link between the geomagnetic field and the Earth's climate in the past and on the physical mechanism involved because, thanks to the application of the transfer entropy, we have determined that the sense of the connection seems to go from the system that produces geomagnetic field to the climate system. Of course, the connection does not mean that the geomagnetic field is fully responsible for the climate changes, rather that it is an important driving component to the variations of the climate.

Multi-centennial fluctuations of radionuclide production rates are modulated by the Earth's magnetic field.

The production of cosmogenic isotopes offers a unique way to reconstruct solar activity during the Holocene. It is influenced by both the solar and Earth magnetic fields and thus their combined effect needs to be disentangled to infer past solar irradiance. Nowadays, it is assumed that the long-term variations of cosmogenic production are modulated by the geomagnetic field and that the solar field dominates over shorter wavelengths. In this process, the effects of the non-dipolar terms of the geomagnetic field are considered negligible. Here we analyse these assumptions and demonstrate that, for a constant solar modulation potential, the geomagnetic field exerts a strong modulation of multi-centennial to millennial wavelengths (periods of 800 and 2200 yr). Moreover, we demonstrate that the non-dipole terms derived from the harmonic degree 3 and above produce maximum differences of 7% in the global average radiocarbon production rate. The results are supported by the identification, for the first time, of a robust coherence between the production rates independently estimated from geomagnetic reconstructions and that inferred from natural archives. This implies the need to review past solar forcing reconstructions, with important implications both for the assessment of solar-climate relationships as well as for the present and future generation of paleoclimate models.

Highlighting the importance of transitional ventilation regimes in the management of Mediterranean show caves (Nerja-Pintada system, southern Spain).

This study shows the utilization of the air CO2 exhaled by a very high number of visitors in the Nerja Cave as both a tracer and an additional tool to precisely evaluate the air circulation through the entire karst system, which includes non-touristic passages, originally free of anthropogenic CO2. The analysis of the temporal - spatial evolution of the CO2 content and other monitoring data measured from January 2015 to December 2016 in the Nerja-Pintada system, including air microbiological controls, has allowed us to define a new general ventilation model, of great interest for the conservation of the subterranean environment. During the annual cycle four different ventilation regimes and two ventilation modes (UAF-mode and DAF-mode) exist which determine the significance of the anthropogenic impact within the caves. During the winter regime, the strong ventilation regime and the airflow directions from the lowest to the highest entrance (UAF-mode) contribute to the rapid elimination of anthropogenic CO2, and this affects the whole karstic system. During the summer regime the DAF-mode ventilation (with airflows from the highest to the lowest entrances) is activated. Although the number of visitors is maximum and the natural ventilation of the karstic system is the lowest of the annual cycle, the anthropogenic impact only affects the Tourist Galleries. The transitional ventilation regimes -spring and autumn- are the most complex of the annual cycle, with changing air-flow directions (from UAF-mode to DAF-mode and vice versa) at diurnal and poly diurnal scale, which conditions the range of the anthropogenic impact in each sector of the karst system. The activation of the DAF-mode has been observed when the temperature difference between the external and air cave is higher than 5°C.

Comparison of myocardial damage among dogs at different stages of clinical leishmaniasis and dogs with idiopathic chronic kidney disease.

Canine leishmaniasis (CanL) is a systemic disease caused by the protozoan parasite Leishmania infantum. Myocarditis in CanL has been described previously in CanL by histopathological analysis of post-mortem specimens and by evaluation of cardiac troponin I (cTnI) levels. However, the degree of myocardial damage at different stages of CanL and the role that concurrent azotaemia plays in this myocardial injury are unknown. The aim of this study was to prospectively evaluate and compare the presence of myocardial injury in dogs at different stages of clinical CanL and in dogs with severe idiopathic chronic kidney disease (CKD) by measuring cTnI. Forty-eight dogs were included in the study, divided into four groups: (1) group A (10 healthy dogs); (2) group B (17 dogs with CanL without renal azotaemia, classified as mild to severe in the LeishVet scheme); (3) group C (11 dogs with CanL and renal azotaemia, classified as very severe in the LeishVet scheme); and (4) group D (10 dogs with idiopathic CKD). Dogs in group C had significantly higher cTnI than dogs in groups B and D, although cTnI was also elevated in these groups. Dogs in group A had normal cTnI values. Dogs in groups D and C had similar renal IRIS classification scorers. Severe lymphoplasmocytic myocarditis and a positive real time PCR of L. infantum DNA were observed in all dogs in group C. Dogs with very severe CanL exhibit more myocardial injury than dogs with milder CanL or dogs with idiopathic CKD.

Breast Cancer Immunology and Immunotherapy: Current Status and Future Perspectives.

Cancer immunology has gained renewed interest in the past few years due to emerging findings on mechanisms involved in tumoral immune evasion. Indisputably, immune edition is currently considered a critical hallmark of cancer. Basic research has revealed new targets which can be modulated in the clinical setting with new compounds and strategies. As recent evidence confirms, breast cancer (BC) is a complex and heterogeneous disease in which host immune responses play a substantial role. T-infiltrating lymphocytes measurement is suggested as a powerful new tool necessary to predict early BC evolution, especially in HER2-positive and triple negative subtypes. However, T-infiltrating lymphocytes, genomic platforms, and many other biomarkers in tissue and peripheral blood (e.g., regulatory T cells and myeloid-derived suppressor cells) are not the only factors being evaluated regarding their potential role as prognostic and/or predictive factors. Many ongoing clinical trials are exploring the activity of immune checkpoint modulators in BC treatment, both in the advanced and neoadjuvant setting. Although this field is expanding with exciting new discoveries and promising clinical results-and creating great expectations-there remain many uncertainties yet to be addressed satisfactorily before this long awaited therapeutic promise can come to fruition.

Conducta de los profesionales sanitarios ante las recomendaciones de profilaxis de endocarditis infecciosa en nuestro medio: ¿se siguen las guías? / Behaviour of health professionals concerning the recommendations for prophylaxis for infectious endocarditis in our setting: Are the guidelines followed?

Objetivos. Las pautas de profilaxis de endocarditis infecciosa recomendadas por las guías de práctica clínica han cambiado recientemente. Se desconoce en nuestro medio si se siguen correctamente las pautas actuales. Nuestro objetivo es describir las actitudes de diferentes profesionales sanitarios ante ellas. Material y métodos. Hemos realizado una encuesta en Córdoba, mediante un cuestionario online con 16 ítems sobre este tema. Se seleccionó aleatoriamente una muestra de 180 profesionales (20 cardiólogos, 80 dentistas, 80 médicos de atención primaria), de la cual contestaron 173. Resultados. La mitad eran varones, teniendo más de 20 años de ejercicio profesional el 52%. El 88,3% consideró que la profilaxis de endocarditis es efectiva (cardiólogos, 77,8%, dentistas, 93,7%, p=0,086). En general, se realiza profilaxis en las situaciones de riesgo claramente establecidas (>90% de los encuestados), pero también en una alta proporción de casos sin riesgo de endocarditis, que oscila entre el 30 y el 60% según los procedimientos (más los dentistas, entre el 36 y 67%, seguidos de los médicos de atención primaria, entre el 28 y 59%). Las pautas antibióticas usadas son muy variadas, siendo los médicos de primaria los que se alejan más de lo recomendado (solo un 25,8% usaban la pauta recomendada, frente a un 54,4% de dentistas y un 72,2% de cardiólogos, p=0,002). Conclusiones. El seguimiento de las recomendaciones sobre profilaxis de endocarditis debe mejorarse en nuestro medio, observándose una tendencia, sobre todo en no cardiólogos, a una «sobreindicación» de la misma (AU)

Objectives. The prophylaxis regimens for infectious endocarditis recommended by the clinical practice guidelines have recently changed. We do not know whether the current regimens are correctly followed in our setting. Our objective was to describe the approaches of various health professionals concerning these guidelines. Material and methods. We conducted a survey in Cordoba, using a 16-item online questionnaire on this topic. We randomly selected a sample of 180 practitioners (20 cardiologists, 80 dentists and 80 primary care physicians), of whom 173 responded. Results. Half of the participants were men; 52% had more than 20 years of professional experience. Some 88.3% of the participants considered that prophylaxis of endocarditis is effective (77.8% of the cardiologists, 93.7% of the dentist; p=.086). In general, prophylaxis is performed in conditions of clearly established risk (>90% of those surveyed). However, prophylaxis is also performed in a high proportion of cases with no risk of endocarditis, varying between 30 and 60% according to the procedure (mostly the dentists, between 36 and 67%, followed by the primary care physicians, between 28 and 59%). The antibiotic regimens employed varied significantly. The primary care physicians were furthest from the recommended regimen (only 25.8% used the recommended regimen vs. 54.4% of dentists and 72.2% of cardiologists; p=.002). Conclusions. Compliance with the recommendations on prophylaxis for endocarditis should be improved in our setting. We observed a tendency, especially among noncardiologists, to 'overindicate' the prophylaxis (AU)

Effectiveness and safety of continuous ultrasound-guided femoral nerve block versus epidural analgesia after total knee arthroplasty. / Eficacia y seguridad del bloqueo femoral continuo guiado con ecografía frente a la analgesia epidural en el postoperatorio de artroplastia total de rodilla.

OBJECTIVES: Total knee arthroplasty is associated with severe postoperative pain. The aim of this study was to compare continuous ultrasound-guided femoral nerve block with continuous epidural analgesia, both with low concentrations of local anaesthetic after total knee arthroplasty. MATERIAL AND METHODS: A prospective, randomised, unblinded study of 60 patients undergoing total knee replacement, randomised into two groups. A total of 30 patients received continuous epidural block, while the other 30 received continuous ultrasound-guided femoral nerve block, as well as using 0.125% levobupivacaine infusion in both groups. Differences in pain control, undesirable effects, and complications between the two techniques were assessed, as well as the need for opioid rescue and the level of satisfaction with the treatment received during the first 48hours after surgery. RESULTS: No differences were found in demographic and surgical variables. The quality of analgesia was similar in both groups, although in the first six hours after surgery, patients in the epidural group had less pain both at rest and with movement (P=.007 and P=.011). This difference was not observed at 24hours (P=.084 and P=.942). Pain control at rest in the femoral block group was better at 48hours after surgery than in the epidural group (P=.009). The mean consumption of morphine and level of satisfaction were similar. Epidural analgesia showed the highest rate of side effects (P=.003). CONCLUSIONS: Continuous ultrasound-guided femoral nerve block provides analgesia and morphine consumption similar to epidural analgesia, with the same level of satisfaction, but with a lower rate of side effects after total knee arthroplasty.

Behaviour of health professionals concerning the recommendations for prophylaxis for infectious endocarditis in our setting: Are the guidelines followed? / Conducta de los profesionales sanitarios ante las recomendaciones de profilaxis de endocarditis infecciosa en nuestro medio: ¿se siguen las guías?

OBJECTIVES: The prophylaxis regimens for infectious endocarditis recommended by the clinical practice guidelines have recently changed. We do not know whether the current regimens are correctly followed in our setting. Our objective was to describe the approaches of various health professionals concerning these guidelines. MATERIAL AND METHODS: We conducted a survey in Cordoba, using a 16-item online questionnaire on this topic. We randomly selected a sample of 180 practitioners (20 cardiologists, 80 dentists and 80 primary care physicians), of whom 173 responded. RESULTS: Half of the participants were men; 52% had more than 20 years of professional experience. Some 88.3% of the participants considered that prophylaxis of endocarditis is effective (77.8% of the cardiologists, 93.7% of the dentist; p=.086). In general, prophylaxis is performed in conditions of clearly established risk (>90% of those surveyed). However, prophylaxis is also performed in a high proportion of cases with no risk of endocarditis, varying between 30 and 60% according to the procedure (mostly the dentists, between 36 and 67%, followed by the primary care physicians, between 28 and 59%). The antibiotic regimens employed varied significantly. The primary care physicians were furthest from the recommended regimen (only 25.8% used the recommended regimen vs. 54.4% of dentists and 72.2% of cardiologists; p=.002). CONCLUSIONS: Compliance with the recommendations on prophylaxis for endocarditis should be improved in our setting. We observed a tendency, especially among noncardiologists, to "overindicate" the prophylaxis.