Post-Ureteroscopic Lesion Scale: limitaciones en su aplicabilidad clínica / Post-Ureteroscopic Lesion Scale to determine ureteral wall damage, not so easy to employ

Objetivo Analizar el nivel de concordancia de la Post-Ureteroscopic Lesion Scale (PULS), y examinar las consecuencias de su aplicación en la práctica clínica con datos estadísticos más fiables que los utilizados en el trabajo original. Métodos Se realizaron 14 ureteroscopias (URS) y 14 micro-ureteroscopias (micro-URS) en 14 cerdos hembra. Todos los procedimientos se grabaron en vídeo y se realizó un análisis anatomopatológico en cada uréter. Dieciséis urólogos (9 endourólogos y 7 urólogos generales) y 4 médicos internos residentes evaluaron las lesiones ureterales según la escala PULS, con grados 0, 1 y ≥2. La concordancia se calculó mediante porcentajes, el Coeficiente W de Kendall, el índice kappa de Fleiss y el alfa de Krippendorff. La concordancia entre evaluadores se calculó con la Correlación de Spearman y el Coeficiente kappa de Cohen. Resultados El porcentaje de concordancia fue del 11,1%. Los coeficientes se clasificaron como bajos o muy bajos, y encontramos una mayor concordancia entre los evaluadores más inexpertos. Por otro lado, no hubo acuerdo entre el 50% de los evaluadores. Conclusiones La baja concordancia entre evaluadores, la especificidad de la PULS y la correlación clínico/patológica sugieren dificultades del uso de esta escala y una curva de aprendizaje probablemente larga. (AU)

Objective To analyze the level of agreement of the Post-Ureteroscopic Lesion Scale (PULS) and the consequences on its application in clinical practice with more reliable statistical data than the one used in the original work. Methods 14 URS and 14 micro-URS were performed in 14 female porcine model. All the procedures were video recorded and an anatomopathological analysis was performed in each ureter. Sixteen urologists (9 endourologists and 7 general urologists) and 4 residents evaluated the ureteral lesions according to the PULS, with degrees 0, 1 and ≥2. The agreement was calculated with percentages, Kendall's W coefficient and the indicators Fleiss’ Kappa and Krippendorff's Alpha, while the inter-rater agreement was calculated with Spearman's correlation and Cohen's Kappa. Results The percent of agreement was 11.1%. The coefficients were likewise classified as low or very low, with the greatest agreement found among the inexperienced. Also, 50% of the raters did not agree with the rest. Conclusions The low inter-rater agreement, the specificity of the PULS and the clinical-pathological correlation suggests that this scale is not simple, and probably has a long learning curve. (AU)

Post-Ureteroscopic Lesion Scale to determine ureteral wall damage, not so easy to employ.

OBJECTIVE: To analyze the level of agreement of the Post-Ureteroscopy Lesion Scale (PULS) and the consequences on its application in clinical practice with more reliable statistical data than the one used in the original work. METHODS: 14 URS and 14 micro-URS were performed in 14 female porcine model. All the procedures were video recorded and an anatomopathological analysis was performed in each ureter. Sixteen urologists (9 endourologists and 7 general urologists) and 4 residents evaluated the ureteral lesions according to the PULS, with degrees 0, 1 and ≥2. The agreement was calculated with percentages, Kendall's W coefficient and the indicators Fleiss' Kappa and Krippendorff's Alpha, while the inter-rater agreement was calculated with Spearman's correlation and Cohen's Kappa. RESULTS: The percent of agreement was 11.1%. The coefficients were likewise classified as low or very low, with the greatest agreement found among the inexperienced. Also, 50% of the raters did not agree with the rest. CONCLUSIONS: The low inter-rater agreement, the specificity of the PULS and the clinical-pathological correlation suggests that this scale is not simple, and probably has a long learning curve.

Impacto clínico de cumplimentar un protocolo de tratamiento nutricional en pacientes críticos afectados por SARS-CoV-2 / The clinical impact of implementation of a nutritional treatment protocol in critically ill adults with SARS-CoV-2 infection

Introducción: El paciente crítico afectado por SARS-CoV-2 tiene riesgo de desnutrición. La necesidad de evitar la sobrecarga de volumen y las maniobras que retrasan el logro de los requerimientos nutricionales como la pronación hacen que el abordaje nutricional de estos sujetos sea complejo. Para asegurar un tratamiento adecuado, se desarrolló un protocolo de soporte nutricional como guía de práctica clínica adaptado al paciente con COVID-19. Objetivo: Describir el protocolo de soporte nutricional creado en nuestro centro, el cumplimiento del mismo y analizar los resultados de su aplicación en los pacientes con SARS-CoV-2, ingresados en la unidad de cuidados intensivos (UCI) del Consorcio Hospital General Universitario de Valencia (CHGUV) de marzo a mayo del 2020. Material y métodos: Diseño observacional, descriptivo, retrospectivo y longitudinal para evaluar el cumplimiento de un protocolo de soporte nutricional. Resultados: Se incluyeron 31 pacientes. No se pudo establecer un seguimiento nutricional en ocho de ellos. De los 23 restantes, ocho alcanzaron 80% de los requerimientos calóricos antes del décimo día tras el inicio del tratamiento (grupo buen cumplimiento) y 15 a partir del undécimo día (grupo mal cumplimiento). El grupo con buen cumplimiento obtuvo 75% (n = 6) de curación y 25% de éxitus (n = 2), en comparación con el grupo con «mal cumplimiento» donde 53% (n = 8) fueron dados de alta a planta vs. 47% (n = 7) que fallecieron (prueba X2, valor p = 0,019). Aquellos pacientes que alcanzaron 80% de las necesidades calóricas en algún momento del ingreso en UCI tuvieron menor duración de la hospitalización frente a los que no lo obtuvieron (mediana de días de ingreso = 14, rango intercuartílico [IQR] = 10-16 y mediana de días de ingreso = 22, IQR = 13-39, valor p = 0,025)...(AU)

Introduction: The critical patient affected by SARS-CoV-2 is at risk of malnutrition. The need to avoid volume overload and manoeuvres that delay reaching nutritional requirements such as pronation make the nutritional approach to these patients complex. To ensure adequate treatment, a nutritional support protocol was developed as a clinical practice guideline adapted to the COVID-19 patient. Objective: To describe and analyse the results of introducing a nutritional support protocol aimed at SARS-CoV-2 patients admitted to the intensive care unit (ICU) of the Consorcio Hospital General Universitario de Valencia (CHGUV) from March to May 2020. Material and methods: Observational, descriptive, retrospective and longitudinal design to evaluate compliance with a nutritional support protocol. Results: Thirty-one consecutive patients were included but nutritional follow-up could not be performed in eight. Of the remaining 23 patients, only eight reached 80% of caloric requirements before the tenth day after starting treatment (good compliance group) and 15 after the eleventh day (poor compliance group). In the group with «good compliance» 75% (n = 6) were discharged and 25% died (n = 2), compared to the group with «bad compliance» where 53% (n = 8) were discharged and 47% (n = 7) died (Chi square test, p-value = 0.019). Those patients who reached 80% of caloric needs during ICU stay had a shorter length of stay compared to those who did not (median days of admission = 14, IQR = 10-16 and median days of admission = 22, IQR = 13-39, p-value = 0.025). Conclusions: Introducing a nutritional protocol during the first weeks of the SARS-CoV-2 pandemic could improve clinical outcomes by promoting healing and reducing associated complications. (AU)

The clinical impact of implementation of a nutritional treatment protocol in critically ill adults with SARS-CoV-2 infection.

INTRODUCTION: The critical patient affected by SARS-CoV-2 is at risk of malnutrition. The need to avoid volume overload and manoeuvres that delay reaching nutritional requirements such as pronation make the nutritional approach to these patients complex. To ensure adequate treatment, a nutritional support protocol was developed as a clinical practice guideline adapted to the COVID-19 patient. OBJECTIVE: To describe and analyse the results of introducing a nutritional support protocol aimed at SARS-CoV-2 patients admitted to the intensive care unit (ICU) of the Consorcio Hospital General Universitario de Valencia (CHGUV) from March to May 2020. MATERIAL AND METHODS: Observational, descriptive, retrospective and longitudinal design to evaluate compliance with a nutritional support protocol. RESULTS: Thirty-one consecutive patients were included but nutritional follow-up could not be performed in eight. Of the remaining 23 patients, only eight reached 80% of caloric requirements before the tenth day after starting treatment (good compliance group) and 15 after the eleventh day (poor compliance group). In the group with «good compliance¼ 75% (n=6) were discharged and 25% died (n=2), compared to the group with «bad compliance¼ where 53% (n=8) were discharged and 47% (n=7) died (Chi square test, p-value=0.019). Those patients who reached 80% of caloric needs during ICU stay had a shorter length of stay compared to those who did not (median days of admission=14, IQR=10-16 and median days of admission=22, IQR=13-39, p-value=0.025). CONCLUSIONS: Introducing a nutritional protocol during the first weeks of the SARS-CoV-2 pandemic could improve clinical outcomes by promoting healing and reducing associated complications.

[The clinical impact of implementation of a nutritional treatment protocol in critically ill adults with SARS-CoV-2 infection]. / Impacto clínico de cumplimentar un protocolo de tratamiento nutricional en pacientes críticos afectados por SARS-CoV-2.

Introduction: The critical patient affected by SARS-CoV-2 is at risk of malnutrition. The need to avoid volume overload and manoeuvres that delay reaching nutritional requirements such as pronation make the nutritional approach to these patients complex. To ensure adequate treatment, a nutritional support protocol was developed as a clinical practice guideline adapted to the COVID-19 patient. Objective: To describe and analyse the results of introducing a nutritional support protocol aimed at SARS-CoV-2 patients admitted to the intensive care unit (ICU) of the Consorcio Hospital General Universitario de Valencia (CHGUV) from March to May 2020. Material and methods: Observational, descriptive, retrospective and longitudinal design to evaluate compliance with a nutritional support protocol. Results: Thirty-one consecutive patients were included but nutritional follow-up could not be performed in eight. Of the remaining 23 patients, only eight reached 80% of caloric requirements before the tenth day after starting treatment (good compliance group) and 15 after the eleventh day (poor compliance group). In the group with «good compliance¼ 75% (n = 6) were discharged and 25% died (n = 2), compared to the group with «bad compliance¼ where 53% (n = 8) were discharged and 47% (n = 7) died (Chi square test, p-value = 0.019). Those patients who reached 80% of caloric needs during ICU stay had a shorter length of stay compared to those who did not (median days of admission = 14, IQR = 10-16 and median days of admission = 22, IQR = 13-39, p-value = 0.025). Conclusions: Introducing a nutritional protocol during the first weeks of the SARS-CoV-2 pandemic could improve clinical outcomes by promoting healing and reducing associated complications.

Risk scores' performance and their impact on operative decision-making in left-sided endocarditis: a cohort study.

The accuracy of contemporary risk scores in predicting perioperative mortality in infective endocarditis (IE) remains controversial. The aim is to evaluate the performance of existent mortality risk scores for cardiovascular surgery in IE and the impact on operability at high-risk thresholds. A single-center retrospective review of adult patients diagnosed with acute left-sided IE undergoing surgery from May 2014 to August 2019 (n = 142) was done. Individualized risk calculation was obtained according to the available mortality risk scores: EuroScore I and II, PALSUSE, Risk-E, Costa, De Feo-Cotrufo, AEPEI, STS-risk, STS-IE, APORTEI, and ICE-PCS scores. A cross-validation analysis was performed on the score with the best area under the curve (AUC). The 30-day survival was 96.5% (95%CI 91-98%). The score with worse area under the curve (AUC = 0.6) was the STS-IE score, while the higher was for the RISK-E score (AUC = 0.89). The AUC of the majority of risk scores suggested acceptable performance; however, statistically significant differences in expected versus observed mortalities were common. The cross-validation analysis showed that a large number of survivors (> 75%) would not have been operated if arbitrary high-risk threshold estimates had been used to deny surgery. The observed mortality in our cohort is significantly lower than is predicted by contemporary risk scores. Despite the reasonable numeric performance of the analyzed scores, their utility in judging the operability of a given patient remains questionable, as demonstrated in the cross-validation analysis. Future guidelines may advise that denial of surgery should only follow a highly experienced Endocarditis Team evaluation.

Development of castration resistance in prostate cancer patients treated with luteinizing hormone-releasing hormone analogues (LHRHa): results of the ANARESISTANCE study.

PURPOSE: Evaluate the percentage of patients with prostate cancer treated with luteinizing hormone-releasing hormone analogues (LHRHa) that develop castration resistance after a follow-up period of 3 years. The secondary objective is to evaluate the variables potentially related to the progression to castration resistant prostate cancer (CRPC). METHODS: A post-authorization, nation-wide, multicenter, prospective, observational, and longitudinal study that included 416 patients treated with LHRHa between 2012 and 2017 is presented. Patients were followed for 3 years or until development of CRPC, thus completing a per-protocol population of 350 patients. A Cox regression analysis was carried out to evaluate factors involved in progression to CRPC. RESULTS: After 3 years of treatment with LHRHa 18.2% of patients developed CRPC. In contrast, in the subgroup analysis, 39.6% of the metastatic patients developed CRPC, compared with 8.8% of the non-metastatic patients. The patients with the highest risk of developing CRPC were those with a nadir prostate-specific antigen (PSA) > 2 ng/ml (HR 21.6; 95% CI 11.7-39.8; p < 0.001) and those receiving concomitant medication, most commonly bicalutamide (HR 1.8; 95% CI 1-3.1, p = 0.0431). CONCLUSIONS: The proportion of metastatic patients developing CRPC after 3 years of treatment with LHRHa is consistent with what has been previously described in the literature. In addition, this study provides new findings on CRPC in non-metastatic patients. Concomitant medication and nadir PSA are statistically significant predictive factors for the time to diagnosis of CRPC, the nadir PSA being the strongest predictor.

Cellular Toxicity Mechanisms and the Role of Autophagy in Pt(IV) Prodrug-Loaded Ultrasmall Iron Oxide Nanoparticles Used for Enhanced Drug Delivery.

Ultrasmall iron oxide nanoparticles (<10 nm) were loaded with cis-diamminetetrachloroplatinum (IV), a cisplatin (II) prodrug, and used as an efficient nanodelivery system in cell models. To gain further insight into their behavior in ovarian cancer cells, the level of cellular incorporation as well as the platination of mitochondrial and nuclear DNA were measured using inductively coupled plasma mass spectrometry (ICP-MS) strategies. Quantitative Pt results revealed that after 24 h exposure to 20 µM Pt in the form of the Pt(IV)-loaded nanoparticles, approximately 10% of the incorporated Pt was associated with nuclear DNA. This concentration increased up to 60% when cells were left to stand in drug-free media for 3 h. These results indicated that the intracellular reducing conditions permitted the slow release of cisplatin (II) from the cisplatin (IV)-loaded nanoparticles. Similar results were obtained for the platination of mitochondrial DNA, which reached levels up to 17,400 ± 75 ng Pt/ mg DNA when cells were left in drug-free media for 3 h, proving that this organelle was also a target for the action of the released cisplatin (II). The time-dependent formation of Pt-DNA adducts could be correlated with the time-dependent decrease in cell viability. Such a decrease in cell viability was correlated with the induction of apoptosis as the main route of cell death. The formation of autophagosomes, although observed upon exposure in treated cells, does not seem to have played an important role as a means for cells to overcome nanoparticles' toxicity. Thus, the designed nanosystem demonstrated high cellular penetration and the "in situ" production of the intracellularly active cisplatin (II), which is able to induce cell death, in a sustained manner.

Endoscopic identification of urinary stone composition: A study of South Eastern Group for Urolithiasis Research (SEGUR 2). / Identificación endoscópica de la composición de los cálculos urinarios: un estudio del Southeastern Group for Lithiasis Research (SEGUR 2).

INTRODUCTION AND OBJECTIVES: To assess the surgeon's ability to evaluate the composition of the stone by observation of endoscopic images. MATERIALS AND METHODS: A series of 20 video clips of endoscopic treatments of urinary stones of which was also available the result of infrared spectroscopy was uploaded to a YouTube site accessible only to members of the South Eastern Group for Urolithiasis Research (SEGUR) who were asked to identify the composition of the stones. RESULTS: A total of 32 clinicians from 9 different countries participated in the study. The average number of correct detections of participants was 7.81 ± 2.68 (range 1-12). Overall accuracy was 39% (250 out of 640 predictions). Calcium oxalate dihydrate stones have been correctly detected in 69.8%, calcium oxalate monohydrate in 41.8%, uric acid in 33.3%, calcium oxalate/uric acid in 34.3% and cystine in 78.1%. Precision rates for struvite (15.6%), calcium phosphate (0%) and mixed calcium oxalate/calcium phosphate (9.3%) were quite low. CONCLUSIONS: Observation of the stone during the endoscopic procedure was not reliable to identify the composition of most stones although it gave some information allowing to identify with a good sensitivity calcium oxalate dihydrate and cystine stones. Nevertheless, photo or video reporting of the intact stone and its internal structure could should be encouraged to implement results of still mandatory post-operative stone analysis. Endourologists should improve their ability of visual identification of the different types of stones.

Incidence of upper tract urothelial carcinoma in Spain. / Incidencia del carcinoma transicional del tracto urinario superior en España.

INTRODUCTION AND OBJECTIVES: The incidence of upper urinary tract tumors is currently unknown. The aim of this study is to determine the real incidence of upper tract urothelial carcinoma (UTUC) in Spain. MATERIAL AND METHODS: A descriptive, prospective and multicenter epidemiological study was conducted in 31 Spanish facilities by means of the Platform for Multicenter Studies of the Spanish Association of Urology. Recruitment was opened from May 1st, 2017 to April 30th, 2018. The original database was exported directly from the electronic Data Collection Logbook on December 15th, 2018, with a total of 404 cases registered (402 valid cases after depuration). Statistical analysis was performed using IBM SPSS software v 23 and EPIDAT v 3.4. RESULTS: The incidence adjusted to Spanish population from raw data was 3.27 cases per 100.000 inhabitants per year (2.93 - 3.61 95% CI) and 3,3 cases per 100.000 inhabitants per year (2.96-3.66 95%CI) when adjusted to European population by age. The mean age at diagnosis was 70 years, and 77% of patients were male. Thirty-four percent of patients had an incidental diagnosis. Tumors were most commonly located in the pyelocalyceal system (54%), followed by the distal ureter (22%). Prior ureteroscopy was performed in 114 patients: this technique modified the subsequent treatment indication in 58% of cases. Radical nephroureterectomy was performed in 311 patients. Kidney-sparing surgery was the elected treatment in 76 patients (20%). Complications were found in 69% of cases, most of them classified as Clavien 1 and 2 (86% of all complications). Postoperative mortality rate was 1.7%. CONCLUSIONS: UTUC adjusted incidence rate in Spain is 3.27 and 3.3 in Europe. Prior URS modified the treatment indication in 18% of patients. We found a 69% complication rate and a 1.7% mortality rate.

Complementary techniques (spICP-MS, TEM, and HPLC-ICP-MS) reveal the degradation of 40 nm citrate-stabilized Au nanoparticles in rat liver after intraperitoneal injection.

BACKGROUND: Due to the increased use of engineered nanoparticles (NPs), their tracing in environmental and biological systems is of utmost importance. Besides their accumulation within a biological specimen, little is known about their degradation and transformation into corresponding low-molecular species that might influence any toxicological impact. ANALYTICAL METHODS: Wistar rats underwent intraperitoneal injections of 40 nm citrate-stabilized gold nanoparticles. Different liver samples were analysed for the occurrence of nanoparticles and potential degradation products by means of spICP-MS, TEM and HPLC-ICP-MS. MAIN FINDINGS: Studies using spICP-MS revealed the presence of the originally administrated Au NPs (40 nm diameter) and some evidences of other Au-containing species due to the increased background signal. Images obtained by transmission electron microscopy (TEM) showed the predominant presence of particles of significantly smaller diameter (6 ± 2 nm). As complementary method, HPLC-ICP-MS confirmed the presence of both particle types indicating a degradation of the Au NPs accompanied by detection of low-molecular Au species. CONCLUSIONS: This study underlines that degradation of gold nanoparticles to low-molecular gold species might have to be taken into account in future for studies on their toxicological behaviour and their potential use in clinical applications.

Comparison of isotope pattern deconvolution and calibration curve quantification methods for the determination of estrone and 17ß-estradiol in human serum.

A Liquid Chromatography coupled to tandem mass spectrometry (LC-MS/MS) based method have been developed for the determination of the main estrogen compounds -estrone (E1) and 17ß-estradiol (E2)- in human serum. Two isotope dilution mass spectrometry (IDMS) quantification procedures have been used: a classical calibration curve-based method were compared to a recently developed isotope pattern deconvolution (IPD) method. IPD is based on isotopic abundance measurements and multiple linear regression. Validation was performed in terms of intra-assay repeatability (n = 5), inter-assay reproducibility (n = 9) and accuracy using spiked steroid-free serum at 5 concentration levels and 3 certified reference materials. Both methodologies meet EMEA requirements yielding recoveries between 79-106% and coefficient of variations of 1.7-8.3% along all experiments. Limits of quantification as low as 5 ng/L were achieved. 40 real samples were analysed for comparison purposes showing a great correlation between calibration and IPD concentration values. Real samples were also quantified by routine immunoassay analysis, which showed a significant proportional bias of 2.55 for E1 and good correlation for E2. While methods were considered suitable for routine or countercheck analysis within the context of hospital's needs, IPD has demonstrated to be faster and cost saving.

Quantitative assessment of the metabolic products of iron oxide nanoparticles to be used as iron supplements in cell cultures.

Iron nanoparticles (NPs) metabolism is directly associated to human health due to their use as anemia treatment and should be studied in detail in cells. Here we present a speciation strategy for the determination of the metabolic products of iron oxide nanoparticles coated by tartaric and adipic acids in enterocytes-like cell models (Caco-2 and HT-29). Such methodology is based on the use of SDS-modified reversed phase high performance liquid chromatography (HPLC) separation using inductively coupled plasma-mass spectrometry (ICP-MS) as Fe selective detector. Post-column isotope dilution analysis is used as quantification tool by adding 57Fe as isotopically enriched standard. To assess the separation capability of the method, two different iron nanostructures: iron sucrose nanoparticles -Venofer®- used as model suspension and iron tartrate/adipate-modified nanoparticles, both of about 4 nm (core size) were evaluated. The two nanostructures were injected into the system showing good peak profiles and quantitative elution recoveries (>80%) in both cases. In addition, both nanoparticulate fractions could be based-line separated from ionic iron species, which needed to be complexed with 1 mM citrate to elute from the column. Exposed cells up to 0.5 mM of iron tartrate/adipate-modified nanoparticles were specifically treated to extract the internalized NPs and the extracts examined using the proposed strategy. The obtained results revealed the presence of three different fractions corresponding to nanoparticle aggregates, dispersed nanoparticles and soluble iron respectively in a single chromatographic run. Quantitative experiments (column recoveries ranging from 60 to 80%) revealed the presence of the majority of the Fe in the nanoparticulated form (>75%) by summing up the dispersed and aggregate particles. Such experiments point out the high uptake and low solubilization rate of the tartrate/adipate NPs making these structures highly suitable as Fe supplements in oral anemia treatments.

Buckwheat and buckwheat enriched products exert an anti-inflammatory effect on the myofibroblasts of colon CCD-18Co.

Buckwheat (BW) constitutes a good source of bioactive components that show anti-inflammatory effects in vitro and in vivo. The use of functional foods in the prevention and treatment of inflammatory bowel diseases (IBDs) has aroused increasing interest. This study investigates the effect of in vitro digested BW and BW-enriched products (BW-enriched wheat breads, roasted BW groats -fermented and non-fermented-, and BW sprouts) on colon myofibroblasts, the cells involved in the regulation of inflammatory response in the intestine. The cells were treated with different digested-BW products, alone or together with TNF-α (20 ng mL-1), and the effects on the cell migration, mitochondrial membrane potential and cell cycle, processes altered during intestinal inflammation, were investigated. A significant reduction in TNF-α-induced migration (25.5%, p < 0.05) and attenuation of the TNF-α-altered cell cycle (p < 0.05) was observed in myofibroblasts treated with BW-enriched white wheat bread. These results contribute to extend the beneficial effects derived from BW bioactive compounds, and suggest that BW consumption can exert beneficial effects on IBDs.

The Changing Epidemiology of Infective Endocarditis in the Twenty-First Century.

PURPOSE OF THE REVIEW: Infective endocarditis (IE) is a relatively infrequent infectious disease. It does, however, causes serious morbidity, and its mortality rate has remained unchanged at approximately 25%. Changes in IE risk factors have deeply impacted its epidemiology during recent decades but literature from low-income countries is very scarce. Moreover, prophylaxis guidelines have recently changed and the impact on IE incidence is still unknown. RECENT FINDINGS: In high-income countries, the proportion of IE related to prior rheumatic disease has decreased significantly and has been replaced proportionally by cases related to degenerative valvulopathies, prosthetic valves, and cardiovascular implantable electronic devices. Nosocomial and non-nosocomial-acquired cases have risen, as has the proportion caused by staphylococci, and the median age of patients. In low-income countries, in contrast, rheumatic disease remains the main risk factor, and streptococci the most frequent causative agents. Studies performed to evaluate impact of guidelines changes' have shown contradictory results. The increased complexity of cases in high-income countries has led to the creation of IE teams, involving several specialties. New imaging and microbiological techniques may increase sensitivity for diagnosis and detection of IE cases. In low-income countries, IE remained related to classic risk factors. The consequences of prophylaxis guidelines changes are still undetermined.

Early in vitro development of daptomycin non-susceptibility in high-level aminoglycoside-resistant Enterococcus faecalis predicts the efficacy of the combination of high-dose daptomycin plus ampicillin in an in vivo model of experimental endocarditis.

Background: Previous studies showed development of daptomycin non-susceptibility (DNS: MIC >4 mg/L) in Enterococcus faecalis infections. However, no studies have assessed the efficacy of the combination of daptomycin/ampicillin against E. faecalis strains developing DNS in the experimental endocarditis (EE) model. Objectives: To assess the in vitro and in vivo efficacy of daptomycin at 10 mg/kg/day, daptomycin/ampicillin and ampicillin/ceftriaxone against two high-level aminoglycoside-resistant E. faecalis strains, one developing DNS after in vitro exposure to daptomycin and another that did not (DS). Methods: Subculture of 82 E. faecalis strains from patients with endocarditis with daptomycin MICs, time-kill and in vivo experiments using the EE model. Results: 33% of the strains (27 of 82) displayed DNS after subculture with daptomycin. Daptomycin MIC rose from 0.5-2 to 8-16 mg/L. In time-kill experiments, when using a high inoculum (10 8 cfu/mL), daptomycin/ampicillin was synergistic for one-third of DS strains and none of DNS strains, while ampicillin/ceftriaxone retained synergy in all cases. In the EE model, daptomycin did not significantly reduce cfu/g from vegetations compared with control against either strain, while daptomycin/ampicillin reduced significantly more cfu/g than daptomycin against the DS strain, but not against the DNS strain [2.9 (2.0-4.1) versus 6.1 (4.5-8.0); P = 0.002]. Ampicillin/ceftriaxone was synergistic and bactericidal against both strains, displaying the same activity as daptomycin/ampicillin against the DS strain. Conclusions: Performance of an Etest for daptomycin MIC after subculture with daptomycin inhibitory doses on strains of high-level aminoglycoside-resistant E. faecalis endocarditis may be an easy test to predict the in vivo efficacy of daptomycin/ampicillin.

The associations between physical fitness and cardiometabolic risk and body-size phenotypes in perimenopausal women.

OBJECTIVE: To study the association between physical fitness and body-size phenotypes, and to test which aspects of physical fitness show the greatest independent association with cardiometabolic risk in perimenopausal women. STUDY DESIGN: This cross-sectional study involved 228 women aged 53±5years from southern Spain. MAIN OUTCOME MEASUREMENTS: Physical fitness was assessed by means of the Senior Fitness Test Battery (additionally including handgrip strength and timed up-and-go tests). Anthropometry, resting heart rate, blood pressure and plasma markers of lipid, glycaemic and inflammatory status were measured by standard procedures. The harmonized definition of the 'metabolically healthy but obese' (MHO) phenotype was employed to classify individuals. RESULTS: The overall prevalence of the MHO phenotype was 13% but was 43% among the obese women. Apart from traditional markers, metabolically healthy non-obese women had lower levels of C-reactive protein than women with the other phenotypes (p<0.001), and levels of glycosylated haemoglobin were lower in MHO women than in metabolically abnormal non-obese women (overall p=0.004). Most of the components of physical fitness differed with body-size phenotypes. The 6-min walk and the back-scratch tests presented the most robust differences (both p<0.001). Moreover, the women's performance on the back-scratch (ß=0.32; p<0.001) and the 6-min walk (ß=0.22; p=0.003) tests was independently associated with the clustered cardiometabolic risk. The back-scratch test explained 10% of the variability (step 1, p<0.001), and the final model, which also included the 6-min walk test (step 2, p=0.003), explained 14% of the variability. CONCLUSION: Low upper-body flexibility was the most important fitness indicator of cardiometabolic risk in perimenopausal women, but cardiorespiratory fitness also played an important role.

Enterococcal endocarditis revisited.

The Enterococcus species is the third main cause of infective endocarditis (IE) worldwide, and it is gaining relevance, especially among healthcare-associated cases. Patients with enterococcal IE are older and have more comorbidities than other types of IE. Classical treatment options are limited due to the emergence of high-level aminoglycosides resistance (HLAR), vancomycin resistance and multidrug resistance in some cases. Besides, few new antimicrobial alternatives have shown real efficacy, despite some of them being recommended by major guidelines (including linezolid and daptomycin). Ampicillin plus ceftriaxone 2 g iv./12 h is a good option for Enterococcus faecalis IE caused by HLAR strains, but randomized clinical trials are essential to demonstrate its efficacy for non-HLAR EFIE and to compare it with ampicillin plus short-course gentamicin. The main mechanisms of resistance and treatment options are also reviewed for other enterococcal species.

Interaction between orexin A and cannabinoid system in the lateral hypothalamus of rats and effects of subchronic intraperitoneal administration of cannabinoid receptor inverse agonist on food intake and the nutritive utilization of protein.

Crosstalk may occur between cannabinoids and other systems controlling appetite, since cannabinoid receptors are present in hypothalamic circuits involved in feeding regulation, and likely to interact with orexin. In this study, an immunohistochemical approach was used to examine the effect of the intracerebroventricular administration of cannabinoid receptor inverse agonist AM 251 on orexin neuropeptide in the hypothalamic system. AM-activated neurons were identified using c-Fos as a marker of neuronal activity. The results obtained show that AM 251 decreases orexin A immunoreactivity, and that it increases c-Fos-immunoreactive neurons within the hypothalamus when compared with the vehicle-injected control group. We also studied the effects of subchronic intraperitoneal administration of AM 251 on food intake, body weight, and protein utilization. The administration of AM 251 at 1, 2, or 5 mg/kg led to a significant reduction in food intake, along with a significant decrease in the digestive utilization of protein in the groups injected with 1 and 2 mg/kg. There was a dose-related slowdown in weight gain, especially at the doses of 2 and 5 mg/kg, during the initial days of the trial. The absence of this effect in the pair-fed group reveals that any impairment to digestibility was the result of administering AM 251. These data support our conclusion that hypothalamic orexigenic neuropeptides are involved in the reduction of appetite and mediated by the cannabinoid receptor inverse agonist. Furthermore, the subchronic administration of AM 251, in addition to its effect on food intake, has significant effects on the digestive utilization of protein.

"Knotless" laparoscopic extraperitoneal adenomectomy.

INTRODUCTION: Laparoscopic adenomectomy is a feasible and effective surgical procedure. We have progressively simplified the procedure using barbed sutures and a technique we call "knotless" laparoscopic adenomectomy. We present a prospective, multicenter, descriptive study that reflects the efficacy and safety of this technique in an actual, reproducible clinical practice situation. METHODS: A total of 26 patients with benign prostatic hyperplasia of considerable size (>80cc) underwent "knotless" laparoscopic adenomectomy. This is an extraperitoneal laparoscopic technique with 4 trocars based on the controlled and hemostatic enucleation of the adenoma using ultrasonic scalpels, precise urethral sectioning under direct vision assisted by a urethral plug, trigonization using barbed suture covering the posterior wall of the fascia, capsulorrhaphy with barbed suture and extraction of the morcellated adenoma through the umbilical incision. RESULTS: The median patient age was 69 (54-83)years, the mean prostate volume was 127 (89-245)cc, the mean operative time was 136 (90-315)min, the mean estimated bleeding volume was 200 (120-500)cc and the hospital stay was 3 (2-6)days. All patients experienced improved function in terms of uroflowmetry and International Prostate Symptom Score and quality of life questionnaires. There were complications in 6 patients, 5 of which were minor. CONCLUSIONS: "Knotless" laparoscopic adenomectomy is a procedure with low complexity that combines the advantages of open surgery (lasting functional results and complete extraction of the adenoma) with laparoscopic procedures (reduced bleeding and need for transfusions, shorter hospital stays and reduced morbidity and complications related to the abdominal wall). The use of ultrasonic scalpels and barbed sutures simplifies the procedure and enables a safe and hemostatic technique.