Serum interleukin-15 levels in cancer patients with cachexia

Interleukin-15 (IL-15) has important anabolic effects on muscle protein metabolism through a decrease in the ATP-ubiquitin-dependent proteolytic pathway. The role of IL-15 in human cancer cachexia is unknown. The aim of this study was to assess the relationship between interleukin-15 (IL-15) in cancer patients with cachexia at diagnosis of malignancy and 8 weeks later. An observational study of 21 cancer patients (with and without cachexia) and 8 healthy subjects was conducted. Body composition was measured by leg-to-leg impedance. Serum IL-15 levels were assessed at baseline and after 4 and 8 weeks. Baseline IL-15 values were similar in cancer patients and in healthy subjects. Cancer patients with lower baseline levels of IL-15 (<2 pg/ml) had significantly higher fat mass (%) along the study. Eighteen patients completed the study: five patients showed an increase of 3.7 kg at the end of the study (5.4% of body weight) and showed a mean increase of IL-15 of 1.32 pg/ml (121%) at 4 weeks and 2.32 pg/ml (197%) at 8 weeks, as compared with mean decrease of -4.1 kg (-5.3%) and -0.09 pg/ml (-2.5%) and 0.6 pg/ml (40.8%) in the 13 patients who lost weight (P=0.001 and P=0.022, respectively). Changes of IL-15 at 4 and 8 weeks were directly associated with changes in body weight, body mass index (BMI), fat-free mass and muscle mass (P<0.05), and indirectly associated with percentage of weight loss (P<0.05). In summary, although the results indicate that IL-15 does not have a role in cancer cachexia pathogenesis, the association during evolution between serum IL-15 and changes in weight and muscle mass suggests a possible role of IL-15 as a marker of the body composition response in cancer patients who are losing weight at the time of diagnosisThis study was partially supported by a grant from the Fundación Mutua Madrileñ

Multifamily Determination of Phytohormones and Acidic Herbicides in Fruits and Vegetables by Liquid Chromatography–Tandem Mass Spectrometry under Accredited Conditions

A 7-min multifamily residue method for the simultaneous quantification and confirmation of 8 phytohormones and 27 acidic herbicides in fruit and vegetables using ultra high-performance liquid chromatography (UHPLC) coupled to tandem mass spectrometry (MS/MS) was developed, validated according to SANTE 12682/2019, and accredited according to UNE-EN-ISO/IEC 17025:2017. Due to the special characteristics of these kinds of compounds, a previous step of alkaline hydrolysis was carried out for breaking conjugates that were potentially formed due to the interactions of the analytes with other components present in the matrix. Sample treatment was based on QuEChERS extraction and optimum detection conditions were individually optimized for each analyte. Cucumber (for high water content commodities) and orange (for high acid and high water content samples) were selected as representative matrices. Matrix-matched calibration was used, and all the validation criteria established in the SANTE guidelines were satisfied. Uncertainty estimation for each target compound was included in the validation process. The proposed method was applied to the analysis of more than 450 samples of cucumber, orange, tomato, watermelon, and zucchini during one year. Several compounds, such as 2,4-dichlorophenoxyacetic acid (2,4-D), 4-(3-indolyl)butyric acid (IBA), dichlorprop (2,4-DP), 2-methyl-4-chlorophenoxy acetic acid (MCPA), and triclopyr were found, but always at concentrations lower than the maximum residue level (MRL) regulated by the EU

Biomarkers and polymorphisms in pancreatic neuroendocrine tumors treated with sunitinib

Several circulating biomarkers and single nucleotide polymorphisms (SNPs) have been correlated with efficacy and tolerability to antiangiogenic agents. These associations remain unexplored in well-differentiated, metastatic pancreatic neuroendocrine tumors treated with the multitargeted tyrosine kinase inhibitor sunitinib. We have assessed the effect on tumor response at 6 months, overall survival, progression-free survival and safety of 14 SNPs, and 6 soluble proteins. Forty-three patients were recruited. Two SNPs in the vascular endothelial growth factor receptor 3 (VEGFR-3) gene predicted lower overall survival: rs307826 with hazard ratio (HR) 3.67 (confidence interval [CI] 95%, 1.35-10.00) and rs307821 with HR 3.84 (CI 95%, 1.47-10.0). Interleukin-6 was associated with increased mortality: HR 1.06 (CI 95%, 1.01-1.12), and osteopontin was associated with shorter PFS: HR 1.087 (1.01-1.16), independently of Ki-67. Furthermore, levels of osteopontin remained higher at the end of the study in patients considered non-responders: 38.5 ng/mL vs. responders: 18.7 ng/mL, p-value=0.039. Dynamic upward variations were also observed with respect to IL-8 levels in sunitinib-refractory individuals: 28.5 pg/mL at baseline vs. 38.3 pg/mL at 3 months, p-value=0.024. In conclusion, two VEGFR-3 SNPs as well as various serum biomarkers were associated with diverse clinical outcomes in patients with well-differentiated pancreatic neuroendocrine tumors treated with sunitinib

PBL aplicado a los estudios de Historia del Arte. Elaboración de materiales didácticos para el Grado en Historia del Arte

El Aprendizaje Basado en Proyectos (PBL) es una metodología alternativa y/o complementaria a las nuevas enseñanzas utilizada en muchas universidades del mundo. En el proyecto se ha llevado a cabo, además de un empleo del sistema en las clases, la elaboración de materiales didácticos

Estudio de la expresión de EGFL7 (Epidermal growth factor-like domain-containing protein 7) en la pared venosa de pacientes con enfermedad venosa crónica

La enfermedad venosa crónica (EVC) se trata de una amplia variedad de anomalías del sistema venoso de gran prevalencia en nuestra sociedad. Frecuentemente, se manifiesta en las extremidades inferiores en forma de vena varicosa (VV), cursando como una situación de hipertensión venosa ambulatoria que se agrava conforme progresa la enfermedad. Cada vez más estudios evidencian la importancia de los cambios moleculares y de la matriz extracelular en la fisiopatogenia de la EVC. EGFL-7 (Epidermal growth factor-like domain-containing protein 7) es un componente de gran importancia en el desarrollo y patología del sistema vascular, aunque su papel en la EVC todavía no ha sido esclarecido. Así, el objetivo del presente trabajo es analizar la expresión génica y proteica de EGFL7 en la pared venosa de pacientes con EVC (n=35) y sanos (n=27), mediante la realización de RT-qPCR e immunohistoquímica, respectivamente. Nuestros resultados muestran como existe una disminución en la expresión de EGFL-7 en pacientes con EVC en comparación con las venas de individuos sanos. En su conjunto, nuestro trabajo apoya el papel de EGFL7 en la pérdida de la homeostasis vascular asociada a la EVC. Futuros estudios son necesarios para profundizar en las implicaciones de estos cambios en el tejido venoso patológico, así como el desarrollo de posibles estrategias dirigidas a esta diana.Chronic venous disease (CVD) is a wide variety of anomalies of the venous system that are highly prevalent in our society. Frequently, it manifests in the lower extremities in the form of varicose veins(VV), presenting as a situation of ambulatory venous hypertension that worsens as the disease progresses. More and more studies show the importance of molecular changes and of the extracellular matrix in the pathophysiology of CVD. EGFL-7 (Epidermal growth factor-like domain-containing protein 7) is a component of great importance in the development and pathology of the vascular system, although its role in CVD has not yet been clarified. Thus, the objective of this study is to analyze the gene and proteinexpression of EGFL7 in the venous wall of patients with CVD (n=35) and healthy patients (n=27), by performing RT-qPCR and immunohistochemistry, respectively. Our results show how there is a decrease in the expression of EGFL-7 in patients with CVD compared to the veins of healthy individuals. As a whole, our work supports the role of EGFL7 in the loss of vascular homeostasis associated with CVD. Future studies are necessary to delve into the implications of these changes in the pathological venous tissue, as well as the development of possible strategies aimed at this target

Grado de adherencia y conocimiento previo a la conciliación terapéutica en pacientes en diálisis peritoneal

Producción CientíficaEl empleo de medicamentos implica a pacientes y profesionales sanitarios, y puede dar lugar a errores con importantes repercusiones clínicas. A estos errores contribuyen la pluripatologìa, la polimedicaciòn, la fragmentación del sistema de salud (con múltiples médicos prescriptores sin registro único de salud), así como al desconocimiento del tratamiento por parte del paciente, familiares o cuidadores. Para disminuir estos errores de medicación se han propuesto varios procesos entre los que se incluyen la conciliación de la medicación (crear lista de medicación exacta que recoja todos los fármacos que el paciente toma), revisión del tratamiento (evaluar la lista para adecuación, efectividad, seguridad y conveniencia en conjunción con el estado de salud del paciente) y manejo individualizado de la terapia (comprobando adherencia, conocimiento de fármacos y lista de medicación «en la cartera»

COVID-19 Severity and Survival over Time in Patients with Hematologic Malignancies: A Population-Based Registry Study

Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February–June 2020; n = 769 (66%)) and later (July 2020–February 2021; n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11–0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77; 2.01–3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34; 0.22–0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12; 0.81–1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis.Depto. de MedicinaFac. de MedicinaTRUEFundación Madrileña de Hematología y HemoterapiaFundación Leucemia y LinfomaAsociación Madrileña de Hematología y Hemoterapiapu

Myocardin-Dependent Kv1.5 Channel Expression Prevents Phenotypic Modulation of Human Vessels in Organ Culture

Objective: We have previously described that changes in the expression of Kv channels associate to phenotypic modulation (PM), so that Kv1.3 /Kv1.5 ratio is a landmark of vascular smooth muscle cells (VSMCs) phenotype. Moreover, we demonstrated that the Kv1.3 functional expression is relevant for PM in several types of vascular lesions. Here, we explore the efficacy of Kv1.3 inhibition for the prevention of remodeling in human vessels, and the mechanisms linking the switch in Kv1.3 /Kv1.5 ratio to PM. Approach and Results: Vascular remodeling was explored using organ culture and primary cultures of VSMCs obtained from human vessels. We studied the effects of Kv1.3 inhibition on serum-induced remodeling, as well as the impact of viral vector-mediated overexpression of Kv channels or myocardin knock-down. Kv1.3 blockade prevented remodeling by inhibiting proliferation, migration and extracellular matrix (ECM) secretion. PM activated Kv1.3 via downregulation of Kv1.5. Hence, both Kv1.3 blockers and Kv1.5 overexpression inhibited remodeling in a non-additive fashion. Finally, myocardin knock-down induced vessel remodeling and Kv1.5 downregulation and myocardin overexpression increased Kv1.5, while Kv1.5 overexpression inhibited PM without changing myocardin expression. Conclusions: We demonstrate that Kv1.5 channel gene is a myocardin-regulated, VSMCs contractile marker. Kv1.5 downregulation upon PM leaves Kv1.3 as the dominant Kv1 channel expressed in dedifferentiated cells. We demonstrated that the inhibition of Kv1.3 channel function with selective blockers or by preventing Kv1.5 downregulation can represent an effective, novel strategy for the prevention of intimal hyperplasia and restenosis of the human vessels used for coronary angioplasty procedures.This work was supported by grant BFU2016-75360-R from the Ministerio de Economía y Competitividad (MINECO), to MTPG and JRLL and Junta de Castilla y León Grant VA114P17 to MTPG. MAM and JS are predoctoral fellows of the UVa-Santander. KS was supported by the Swedish Research Council (2017-01225_3

A correlative biomarker study and integrative prognostic model in chemotherapy-naïve metastatic castration-resistant prostate cancer treated with enzalutamide

There is a considerable need to incorporate biomarkers of resistance to new antiandrogen agents in the management of castration-resistant prostate cancer (CRPC). We conducted a phase II trial of enzalutamide in first-line chemo-naïve asymptomatic or minimally symptomatic mCRPC and analyzed the prognostic value of TMPRSS2-ERG and other biomarkers, including circulating tumor cells (CTCs), androgen receptor splice variant (AR-V7) in CTCs and plasma Androgen Receptor copy number gain (AR-gain). These biomarkers were correlated with treatment response and survival outcomes and developed a clinical-molecular prognostic model using penalized cox-proportional hazard model. This model was validated in an independent cohort. Ninety-eight patients were included. TMPRSS2-ERG fusion gene was detected in 32 patients with no differences observed in efficacy outcomes. CTC detection was associated with worse outcome and AR-V7 in CTCs was associated with increased rate of progression as best response. Plasma AR gain was strongly associated with an adverse outcome, with worse median prostate specific antigen (PSA)-PFS (4.2 vs. 14.7 m; p < 0.0001), rad-PFS (4.5 vs. 27.6 m; p < 0.0001), and OS (12.7 vs. 38.1 m; p < 0.0001). The clinical prognostic model developed in PREVAIL was validated (C-Index 0.70) and the addition of plasma AR (C-Index 0.79; p < 0.001) increased its prognostic ability. We generated a parsimonious model including alkaline phosphatase (ALP); PSA and AR gain (C-index 0.78) that was validated in an independent cohort. TMPRSS2-ERG detection did not correlate with differential activity of enzalutamide in first-line mCRPC. However, we observed that CTCs and plasma AR gain were the most relevant biomarkers

Time to –30°C as a predictor of acute success during cryoablation in patients with atrial fibrillation

Background: Freezing rate of second-generation cryoballoon (CB) is a biophysical parameter that could assist pulmonary vein isolation. The aim of this study is to assess freezing rate (time to reach –30°C ([TT-30C]) as an early predictor of acute pulmonary vein isolation using the CB. Methods: Biophysical data from CB freeze applications within a multicenter, nation-wide CB ablation registry were gathered. Successful application (SA), was defined as achieving durable intraprocedural vein isolation with time to isolation in under 60 s (SA-TTI&lt;60) as achieving durable vein isolation in under 60 s. Logistic regressions were performed and predictive models were built for the data set. Results: 12,488 CB applications from 1,733 atrial fibrillation (AF) ablation procedures were included within 27 centers from a Spanish CB AF ablation registry. SA was achieved in 6,349 of 9,178 (69.2%) total freeze applications, and SA-TTI&lt;60 was obtained in 2,673 of 4,784 (55.9%) freezes and electrogram monitoring was present. TT-30C was shorter in the SA group (33.4 ± 9.2 vs 39.3 ± 12.1 s; p &lt; 0.001) and SA-TTI&lt;60 group (31.8 ± 7.6 vs. 38.5 ± 11.5 s; p &lt; 0.001). Also, a 10 s increase in TT-30C was associated with a 41% reduction in the odds for an SA (odds ratio [OR] 0.59; 95% confidence interval [CI] 0.56–0.63) and a 57% reduction in the odds for achieving SA-TTI&lt;60 (OR 0.43; 95% CI 0.39–0.49), when corrected for electrogram visualization, vein position, and application order. Conclusions: Time to reach –30°C is an early predictor of the quality of a CB application and can be used to guide the ablation procedure even in the absence of electrogram monitoring.