Real world data on the demographic and clinicopathological profile and management of patients with early-stage HER2-positive breast cancer and residual disease treated with adjuvant trastuzumab emtansine (KARMA study).

INTRODUCTION: Trastuzumab emtansine (T-DM1) significantly improves invasive disease-free survival and reduces the risk of recurrence in patients with HER2-positive early breast cancer (EBC) with residual disease (RD). The KARMA study aimed to describe the characteristics and management of these patients in clinical practice in Spain. MATERIAL AND METHODS: We conducted a multicentre retrospective study in patients with HER2-positive EBC with RD following neoadjuvant treatment (NeoT) and who had received ≥1 dose of T-DM1 as adjuvant treatment. The primary endpoint was the evaluation of sociodemographic and clinicopathological characteristics of these patients. RESULTS: A total of 114 patients were included (March-July 2020). At diagnosis, most tumours were infiltrating ductal carcinoma (IDC) (93.9 %), grade 2 (56.1 %), and hormone receptor (HR)-positive (79.8 %). Over 75 % of patients had disease in operable clinical stages (T1-3 N0-1). In the neoadjuvant setting, 86.8 % of patients received trastuzumab plus pertuzumab, and 23.6 % achieved radiological complete response. Breast-conserving surgery was performed in 55.8 % of patients. Surgical specimens showed that 89.5 % of patients had IDC, 49.1 % grade 2, 84.1 % HR-positive, and 8.3 % HER2-negative disease. Most patients had RD classified as RCB-II and Miller/Payne grade 3/4. Grade 3 treatment-related adverse events (trAEs) occurred in 5.3 % of patients. No grade 4/5 AEs occurred. Over 95 % of patients were free of invasive-disease during T-DM1 adjuvant treatment. CONCLUSION: The KARMA study describes the characteristics of patients with HER2-positive EBC with RD after NeoT and the real-life management of a T-DM1 adjuvant regimen, which showed a manageable safety profile in line with the KATHERINE trial data.

Tratamientos modificadores de la enfermedad en pacientes con esclerosis múltiple en España / Disease-modifying treatments for patients with multiple sclerosis in Spain

La esclerosis múltiple es una enfermedad desmielinizante crónica del sistema nervioso central y discapacitante a largo plazo. Existen diferentes tratamientos modificadores de la enfermedad. Estos pacientes, a pesar de ser generalmente jóvenes, tienen una elevada comorbilidad y riesgo de polimedicación por su compleja sintomatología y discapacidad. Objetivo principal determinar el tipo de tratamiento modificador de la enfermedad en los pacientes atendidos en servicios de farmacia de hospitales españoles. Objetivos secundarios Conocer los tratamientos concomitantes, determinar la prevalencia de la polifarmacia, identificar la prevalencia de interacciones y analizar la complejidad farmacoterapéutica. Método estudio observacional, transversal y multicéntrico. Se incluyeron todos los pacientes con diagnóstico de esclerosis múltiple y tratamiento modificador de la enfermedad activo a los que se atendió en las consultas de pacientes externos o en los hospitales de día durante la segunda semana de febrero 2021. Se recogieron: el tratamiento modificador, las comorbilidades y los tratamientos concomitantes para determinar el patrón de multimorbilidad, polifarmacia, complejidad farmacoterapéutica (Medication Regimen Complexity Index) e interacciones medicamentosas. Resultados se incluyeron 1.407 pacientes de 57 centros de 15 Comunidades Autónomas. La forma de presentación de la enfermedad más frecuente fue la forma remitente recurrente (89,3%). El tratamiento modificador de la enfermedad más prescrito fue dimetilfumarato (19,1%), seguido de teriflunomida (14,0%). De los tratamientos modificadores parenterales, los 2 más prescritos fueron el acetato de glatiramero y el natalizumab con un 11,1 y 10,8% respectivamente. El 24,7% de los pacientes tenían una comorbilidad y el 39,8% al menos 2 comorbilidades. El 13,3% pertenecía al menos a uno de los patrones definidos de multimorbilidad y el 16,5% pertenecían a 2 o más patrones. ... (AU)

Multiple sclerosis is a chronic demyelinating disease of the central nervous system and long-term disabling. Different disease-modifying treatments are available. These patients, despite being generally young, have high comorbidity and risk of polymedication due to their complex symptomatology and disability.Objective primaryTo determine the type of disease-modifying treatment in patients seen in Spanish hospital pharmacy departments.Secondary objectivesTo determine concomitant treatments, determine the prevalence of polypharmacy, identify the prevalence of interactions and analyse pharmacotherapeutic complexity.MethodObservational, cross-sectional, multicentre study. All patients with a diagnosis of multiple sclerosis and active disease-modifying treatment who were seen in outpatient clinics or day hospitals during the second week of February 2021 were included. Modifying treatment, comorbidities and concomitant treatments were collected to determine multimorbidity pattern, polypharmacy, pharmacotherapeutic complexity (Medication Regimen Complexity Index) and drug-drug interactions.Results1,407 patients from 57 centres in 15 autonomous communities were included. The most frequent form of disease presentation was the relapsing remitting form (89.3%). The most prescribed disease-modifying treatment was dimethyl fumarate (19.1%), followed by teriflunomide (14.0%). Of the parenteral disease-modifying treatments, the two most prescribed were glatiramer acetate and natalizumab with 11.1% and 10.8%. 24.7% of the patients had one comorbidity and 39.8% had at least 2 comorbidities. 13.3% belonged to at least one of the defined patterns of multimorbidity and 16.5% belonged to 2 or more patterns. The concomitant treatments prescribed were psychotropic drugs (35.5%); antiepileptic drugs (13.9%) and antihypertensive drugs and drugs for cardiovascular pathologies (12.4%). ... (AU)

Disease-modifying treatments for patients with multiple sclerosis in Spain. / Tratamientos modificadores de la enfermedad en pacientes con esclerosis múltiple en España.

Multiple sclerosis is a chronic demyelinating disease of the central nervous system and long-term disabling. Different disease-modifying treatments are available. These patients, despite being generally young, have high comorbidity and risk of polymedication due to their complex symptomatology and disability. OBJECTIVE PRIMARY: To determine the type of disease-modifying treatment in patients seen in Spanish hospital pharmacy departments. SECONDARY OBJECTIVES: To determine concomitant treatments, determine the prevalence of polypharmacy, identify the prevalence of interactions and analyse pharmacotherapeutic complexity. METHOD: Observational, cross-sectional, multicentre study. All patients with a diagnosis of multiple sclerosis and active disease-modifying treatment who were seen in outpatient clinics or day hospitals during the second week of February 2021 were included. Modifying treatment, comorbidities and concomitant treatments were collected to determine multimorbidity pattern, polypharmacy, pharmacotherapeutic complexity (Medication Regimen Complexity Index) and drug-drug interactions. RESULTS: 1,407 patients from 57 centres in 15 autonomous communities were included. The most frequent form of disease presentation was the relapsing remitting form (89.3%). The most prescribed disease-modifying treatment was dimethyl fumarate (19.1%), followed by teriflunomide (14.0%). Of the parenteral disease-modifying treatments, the two most prescribed were glatiramer acetate and natalizumab with 11.1% and 10.8%. 24.7% of the patients had one comorbidity and 39.8% had at least 2 comorbidities. 13.3% belonged to at least one of the defined patterns of multimorbidity and 16.5% belonged to 2 or more patterns. The concomitant treatments prescribed were psychotropic drugs (35.5%); antiepileptic drugs (13.9%) and antihypertensive drugs and drugs for cardiovascular pathologies (12.4%). The presence of polypharmacy was 32.7% and extreme polypharmacy 8.1%. The prevalence of interactions was 14.8%. Median pharmacotherapeutic complexity was 8.0 (IQR: 3.3 -- 15.0). CONCLUSIONS: We have described the disease-modifying treatment of patients with multiple sclerosis seen in Spanish pharmacy services and characterised concomitant treatments, the prevalence of polypharmacy, interactions, and their complexity.

EGFR-mutated advanced lung cancer. Data from a single institution, the Hospital of Leon, in Spain.

INTRODUCTION: 10-16% of non-small cell lung cancer (NSCLC) cases have the epidermal growth factor receptor (EGFR) amplified and/or mutated. Studies show that EGFR tyrosine kinase inhibitors (TKIs) significantly prolong progression-free survival (PFS) in patients with advanced NSCLC compared to those treated with platinum-based chemotherapy (CT) doublets. Our aim is to perform a real-world survival analysis of patients treated with TKI as first-line therapy at the Hospital of Leon (CAULE) in Spain. The impact on global survival rates and responses to clinical and histopathological factors were also analyzed. MATERIAL AND METHODS: We retrospectively reviewed patients diagnosed with EGFR-mutated NSCLC who received treatment with EGFR-TKI in the Department of Oncology at the University of Leon Health Center complex between March 2011 and June 2018. Data was analyzed with Kaplan-Meier and Cox regression models to show overall survival (OS), progression-free survival (PFS), and the associated variables. RESULTS: 53 patients were included in the study, 50% (n = 27) were treated with gefitinib, 32% (n = 18) with erlotinib and 10% (n = 6) with afatinib. The median OS and PFS were 27.7 months (95% CI: 21-33.8 months) and 18 months (95% CI 14.25-21.89 months), respectively. The variables associated with OS and with PFS were exon19 deletion as a protective factor and presence of extrathoracic metastasis as a risk factor. The most frequent adverse effects were rash, diarrhea, asthenia, and conjunctivitis. CONCLUSIONS: Real-world analysis of this data confirms that treatment with TKI is beneficial for patients diagnosed with EGFR-mutated NSCLC. Our OS outcomes were similar to those reported in clinical trials.

Challenging Endocrine Sensitivity of Hormone Receptor-Positive/HER2-Negative Advanced Breast Cancer with the Combination of Eribulin and Endocrine Therapy: The REVERT Study.

BACKGROUND: Luminal advanced breast cancer (ABC) patients eventually progress on endocrine therapy. REVERT aimed to explore whether eribulin could restore endocrine sensitivity in a randomized, non-comparative phase II trial. METHODS: Aromatase inhibitor (AI)-resistant patients with luminal ABC were randomized 1:1 to receive eribulin +/- AI. Patients were stratified by prior cyclin-dependent kinases 4/6 inhibitor (CDK4/6i) treatment. The primary endpoint was an investigator-assessed overall response rate (ORR) according to RECIST version 1.1 in the eribulin + AI arm. An interim analysis was planned with 11 evaluable patients according to a two-stage Simon design. RESULTS: Twenty-two patients were enrolled (15 eribulin + AI arm; 7 eribulin arm). The trial was terminated early in March 2021, with eight (36.4%) patients still on treatment. ORR was 26.7% in the eribulin + AI arm (95% CI, 7.8-55.1%; p = 0.0541). In the eribulin arm, two (28.6%) patients had an objective response (95% CI, 3.7-71.0%). The difference between the study arms was not significant (p = 0.918). The addition of AI to eribulin also failed to show improvement in other efficacy endpoints. A significant interaction between the treatment arm and previous CDK4/6i treatment was observed for ORR (p = 0.018) and progression-free survival (p = 0.084). Overall, the toxicity profile was consistent with the known safety profile of eribulin. No treatment-related deaths were reported. CONCLUSION: Eribulin + AI does not seem to improve outcomes compared with eribulin monotherapy in patients with AI-resistant luminal ABC. This chemo-endocrine approach deserves further investigation after progression to CDK4/6i-based therapy.

SOLTI-1904 ACROPOLI TRIAL: efficacy of spartalizumab monotherapy across tumor-types expressing high levels of PD1 mRNA.

Improved selection of cancer patients who are most likely to respond to immune checkpoint inhibitors remains an unmet clinical need. Recently, a positive correlation between levels of PD1 mRNA and clinical outcome in response to PD1 blockade across diverse tumor histologies has been confirmed in several datasets. ACROPOLI is a parallel cohort, non-randomized, phase II study that aims to evaluate the efficacy of the anti-PD1 immune checkpoint inhibitor spartalizumab as monotherapy in metastatic patients with solid tumors that express high levels of PD1 (cohort 1; n = 111). An additional cohort of 30 patients with tumors expressing low levels of PD1, where PD1/PD-L1 antibodies in monotherapy are standard treatment, will also be included (cohort 2). Primary end point is overall response rate in cohort 1. Trial registration number: NCT04802876 (ClinicalTrials.gov).

Relationship between Aldehyde Dehydrogenase, PD-L1 and Tumor-Infiltrating Lymphocytes with Pathologic Response and Survival in Breast Cancer.

Aldehyde dehydrogenase 1A1 (ALDH1A1) is a cancer stem cell (CSC) marker related to clinical outcomes in breast cancer (BC). The aim of this study was to analyze the relationship between ALDH1A1, programmed death ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) in triple negative (TN) and human epidermal growth factor receptor 2-positive (HER2+) BC tumors, and its association with clinicopathological characteristics and outcomes. A retrospective, historical cohort study of patients diagnosed with early or locally advanced BC treated with neoadjuvant chemotherapy was conducted. ALDH1A1, PD-L1 expression and TILs were assessed using immunohistochemistry. A total of 75 patients were analyzed (42.7% TN, 57.3% HER2+ tumors). ALDH1A1+ was related to HTILs (p = 0.005) and PD-L1+ tumors (p = 0.004). ALDH1A1+ tumors presented higher CD3+ (p = 0.008), CD4+ (p = 0.005), CD8+ (p = 0.003) and CD20+ (p = 0.006) TILs. ALDH1A1+ (p = 0.018), PD-L1+ (p = 0.004) and HTILs (p < 0.001) were related to smaller tumors. ALDH1A1+ was related to pathologic complete response (pCR) (p = 0.048). At the end of the follow-up (54.4 [38.3−87.6] months), 47 patients (62.7%) remained disease-free, and 20 (26.7%) had died. HTILs were related to improved disease-free survival (p = 0.027). ALDH1A1+ was related to PD-L1+ and HITLs, that might be related to higher pCR rates with neoadjuvant therapy.

Fatty acid intake and breast cancer in the Spanish multicase-control study on cancer (MCC-Spain).

PURPOSE: To evaluate the association between dietary fat and fat subtype and breast cancer development. METHODS: We conducted a case-control study with 1181 cases of incident breast cancer, diagnosed between 2007 and 2012, and 1682 population controls frequency matched (by age, sex, and region) from the Spanish multicenter case-control study MCC-Spain. RESULTS: We found a significant protective effect in premenopausal women of total fat intake [OR 0.51 95% CI (0.31-0.86) highest versus lowest tertile], but no effect was observed in menopausal women [OR 1.15 95% CI (0.83-1.60)]. Analyzing by type of fat, this protective effect persisted only for the monounsaturated fatty acids [OR 0.51 95% CI (0.32-0.82)]. In contrast, other fatty acids did not have a significant effect. In addition, a protection against risk of breast cancer was found when polyunsaturated fats were "substituted" by monounsaturated, maintaining the same total fat intake [OR 0.68 95% CI (0.47-0.99)]. Finally, analyzing by breast cancer subtype, we found no effect, except in premenopausal women where intake of moderate [OR 0.52 95% CI (0.33-0.82)] and high monounsaturated fatty acids [OR 0.47 95% CI (0.27-0.82)] maintains a protective effect against ER/PR + tumors. In contrast, in menopausal women, a high intake of monounsaturated fatty acids was associated with higher risk of HER2 + tumors [OR 2.00 95% CI (0.97-4.13)]. CONCLUSION: Our study shows a differential effect of monounsaturated fatty acids according to menopausal status and breast cancer subtype.

Oral metronomic vinorelbine combined with endocrine therapy in hormone receptor-positive HER2-negative breast cancer: SOLTI-1501 VENTANA window of opportunity trial.

BACKGROUND: The biological effect of oral metronomic vinorelbine (mVNB) alone or in combination with endocrine therapy in patients with hormone receptor-positive (HR+)/HER2-negative breast cancer has been scarcely addressed. METHODS: Postmenopausal women with untreated stage I-III HR+/HER2-negative breast cancer were randomized (1:1:1) to receive 3 weeks of letrozole (LTZ) 2.5 mg/day, oral mVNB 50 mg 3 days/week, or the combination. The primary objective was to evaluate, within PAM50 Luminal A/B disease, if the anti-proliferative effect of LTZ+mVNB was superior to monotherapy. An anti-proliferative effect was defined as the mean relative decrease of the PAM50 11-gene proliferation score in combination arm vs. both monotherapy arms. Secondary objectives included the evaluation of a comprehensive panel of breast cancer-related genes and safety. An unplanned analysis of stromal tumor-infiltrating lymphocytes (sTILs) was also performed. PAM50 analyses were performed using the nCounter®-based Breast Cancer 360™ gene panel, which includes 752 genes and 32 signatures. RESULTS: Sixty-one patients were randomized, and 54 paired samples (89%) were analyzed. The main patient characteristics were mean age of 67, mean tumor size of 1.7 cm, mean Ki67 of 14.3%, stage I (55.7%), and grades 1-2 (90%). Most baseline samples were PAM50 Luminal A (74.1%) or B (22.2%). The anti-proliferative effect of 3 weeks of LTZ+mVNB (- 73.2%) was superior to both monotherapy arms combined (- 49.9%; p = 0.001) and mVNB (- 19.1%; p < 0.001). The anti-proliferative effect of LTZ+mVNB (- 73.2%) was numerically higher compared to LTZ (- 65.7%) but did not reach statistical significance (p = 0.328). LTZ+mVNB induced high expression of immune-related genes and gene signatures, including CD8 T cell signature and PDL1 gene and low expression of ER-regulated genes (e.g., progesterone receptor) and cell cycle-related and DNA repair genes. In tumors with ≤ 10% sTILs at baseline, a statistically significant increase in sTILs was observed following LTZ (paired analysis p = 0.049) and LTZ+mVNB (p = 0.012). Grade 3 adverse events occurred in 3.4% of the cases. CONCLUSIONS: Short-term mVNB is well-tolerated and presents anti-proliferative activity alone and in combination with LTZ. The high expression of immune-related biological processes and sTILs observed with the combination opens the possibility of studying this combination with immunotherapy. Further investigation comparing these biological results with other metronomic schedules or drug combinations is warranted. TRIAL REGISTRATION: NCT02802748 , registered 16 June 2016.

Safety of eribulin as third-line chemotherapy in HER2-negative, advanced breast cancer pre-treated with taxanes and anthracycline: OnSITE study.

Eribulin is active and safe in heavily pre-treated metastatic breast cancer patients. Few safety data have been published in third line. We aimed to report the specific safety profile on third line beyond taxanes and anthracyclines in advanced breast cancer (ABC). A multicenter phase II, prospective study was conducted in anthracyclines and taxanes pre-treated HER2-negative ABC, programmed to receive eribulin as third-line chemotherapy. Adverse events (AEs) were assessed and classified according to CTCAE. In addition, efficacy, in terms of overall survival (OS) and progression-free survival (PFS), and the dynamics of circulating tumor cells (CTCs) during treatment were assessed. 59 patients fulfilled the criteria. All but one showed AEs with a cumulative number of 598 AEs. The most frequent grade 3/4 drug-related AEs were neutropenia (1.7%), febrile neutropenia (0.5%), leukopenia (0.5%), alopecia (0.5%), asthenia (0.3%), elevated gamma glutamyl transferase levels (0.2%), and respiratory tract infection (0.2%). Median PFS was 4 months (95% CI 3.1-5.9) and median OS was 13.6 months (11.8-not reached). The mean number of CTCs in peripheral blood was significantly reduced from baseline to cycle 2 (16.8 vs 5.4 CTCs; P < 0.001). Median OS was significantly longer in <5 baseline CTC patients compared to ≥5 baseline CTC patients (13.1 months [95% CI: 11.8-not reached] vs 12.5 months [95% CI: 7.6-not reached]; P = 0.045). A significant correlation (P = 0.0129) was observed between CTC levels at cycle 2 and death when CTCs were analyzed using cox regression. Eribulin chemotherapy is effective and safe as third line in advanced HER2-negative breast cancer. CTC levels correlate with overall survival.

A Higher Fructose Intake Is Associated with Greater Albuminuria in Subjects with Type 2 Diabetes Mellitus.

The aim of this single center cross-sectional study was to investigate the association between fructose intake and albuminuria in subjects with type 2 diabetes mellitus (T2DM). This is a single center cross-sectional study. One hundred and forty-three subjects with T2DM were recruited from the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran. The median daily fructose intake was estimated with a prospective food registry during 3 days (2 week-days and one weekend day) and they were divided into low fructose intake (<25 g/day) and high fructose intake (≥ 25 g/day). Complete clinical and biochemical evaluations were performed, including anthropometric variables and a 24-hour urine collection for albuminuria determination. One hundred and thirty-six subjects were analyzed in this study. We found a positive significant association between daily fructose intake and albuminuria (ρ= 0.178, p=0.038) in subjects with type 2 diabetes mellitus. Other variables significantly associated with albuminuria were body mass index (BMI) (ρ= 0.170, p=0.048), mean arterial pressure (MAP) (ρ= 0.280, p=0.001), glycated hemoglobin (A1c) (ρ= 0.197, p=0.022), and triglycerides (ρ= 0.219, p=0.010). After adjustment for confounding variables we found a significant and independent association between fructose intake and albuminuria (ß= 13.96, p=0.006). We found a statistically significant higher albuminuria (60.8 [12.8-228.5] versus 232.2 [27.2-1273.0] mg/day, p 0.002), glycated hemoglobin (8.6±1.61 versus 9.6±2.1 %), p= 0.003, and uric acid (6.27±1.8 versus 7.2±1.5 mg/dL), p=0.012, in the group of high fructose intake versus the group with low fructose intake, and a statistically significant lower creatinine clearance (76.5±30.98 mL/min versus 94.9±36.8, p=0.014) in the group with high fructose intake versus the group with low fructose intake. In summary we found that a higher fructose intake is associated with greater albuminuria in subjects with T2DM.

Experience with eribulin in HR+/HER2- metastatic breast cancer, including a male.

Numerous patient- and disease-related factors must be considered when deciding a treatment approach for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer. Hormone therapy (HT) is generally the first option in the absence of compelling reasons for chemotherapy (e.g., rapidly progressive visceral disease). After failure of first-choice HT, alternative HT options are usually attempted until hormone resistance occurs and chemotherapy becomes the treatment of choice. The first two patients presented herein experienced prolonged disease control with third-line eribulin after two lines of HT. The third report involves a case of male breast cancer which typically presents as the HR+/HER2- phenotype. Eribulin in the second line provided prolonged clinical improvement and was well tolerated.

Catéteres venosos centrales con reservorio subcutáneo de implantación braquial. Una alternativa que tener en cuenta / Central venous catheters with subcutáneous reservoir wit implementation braquial: an alternative to consider

En pacientes con neoplasias, la administración de tratamientos debe realizarse por profesionales de enfermería con experiencia y conocimientos de la patología que se ha de tratar, de los fármacos, de las técnicas y de los dispositivos que se han de utilizar para su administración. La implantación de un dispositivo de acceso venoso con reservorio subcutáneo ofrece la posibilidad de múltiples, frecuentes inyecciones y extracción de sangre. Son estéticamente mejor aceptados que los catéteres externos, tiene menor riesgo de salida accidental e infección, precisan menos cuidados y permiten el tratamiento ambulatorio. Otras ventajas son que causan menos limitaciones de actividad diaria e higiene, lo que se relaciona con un aumento de la calidad de vida. Los resultados de éxito en la colocación y la disminución de las complicaciones mejoraron sensiblemente cuando para su implantación se utiliza fluoroscopia y ultrasonido (entre el 99 % y el 100 %), siendo las complicaciones de la colocación (hemorragia, neumotórax) del 0 %. La tasa de infecciones -trombosis venosa profunda (TVP)- no es llamativa, y permanece dentro de los parámetros normales en relación con los sistemas pectorales. Estos dispositivos son especialmente útiles en pacientes con anormalidades de pared del tórax (carcinoma dérmico de la pared del tórax y corazas tumorales). También cuando existen heridas abiertas de la zona torácica, traqueotomía o fibrosis producida por la radioterapia. Y ante la existencia de cicatrices de los colgajos después de una cirugía en cáncer de cuello (o cuando se prevea que el paciente va a recibir este tratamiento quirúrgico), cifosis severa, pacientes obesos y pacientes con insuficiencia respiratoria (AU)

Administering treatments in patients with malignancies must be performed by nursing professionals with experience and knowledge of the pathology being treated, drugs, techniques and devices used for administration. The implantation of a venous access device with subcutaneous reservoir offers the possibility of multiple and long-term frequent injections and also blood extraction from a less invasive way. They are aesthetically more acceptable than external catheters, they have a lower risk of accidental release and infection, they require less care and they allow extra-hospital treatment. Another advantage to consider is that they cause less limitations in daily life, which is associated with an increased quality of life. Placement of devices with camera of brachial location, was done by the first time by venotomy technique with many doubts; however, the results of placement success and the decreased complications, improved significantly when the placement began performing by vascular radiology services using fluoroscopy and ultrasound. Particularly striking is the success rate (between 99 % and 100 %) with a 0 % rate of placement complications (hemorrhage, pneumothorax). The infection rate is not flashy, remaining within normal parameters in relation to the pectoral systems. The rates of deep vein thrombosis (DVT) are assumable and they are consistent with other related studies. These devices are particularly useful in patients with abnormalities of chest wall such as dermal carcinoma and tumor shell in patients with breast cancer (tumour the bottom shell). And also when there are open wounds in the chest area, such as tracheotomy or fibrosis caused by radiation therapy, or in the presence of scars of flaps after surgery in head and neck cancer (or when it is expected that the patient will receive this surgery), severe kyphosis, obese patients and patients with respiratory failure (AU)

[Central Venous Catheters with Subcutaneous Reservoir with Implementation Braquial: An Alternative to Consider]. / Catéteres venosos centrales con reservorio subcutáneo de implantación braquial.

Administering treatments in patients with malignancies must be performed by nursing professionals with experience and knowledge of the pathology being treated, drugs, techniques and devices used for administration. The implantation of a venous access device with subcutaneous reservoir offers the possibility of multiple and long-term frequent injections and also blood extraction from a less invasive way. They are aesthetically more acceptable than external catheters, they have a lower risk of accidental release and infection, they require less care and they allow extra-hospital treatment. Another advantage to consider is that they cause less limitations in daily life, which is associated with an increased quality of life. Placement of devices with camera of brachial location, was done by the first time by venotomy technique with many doubts; however, the results of placement success and the decreased complications, improved significantly when the placement began performing by vascular radiology services using fluoroscopy and ultrasound. Particularly striking is the success rate (between 99% and 100%) with a 0% rate of placement complications (hemorrhage, pneumothorax). The infection rate is not flashy, remaining within normal parameters in relation to the pectoral systems. The rates of deep vein thrombosis (DVT) are assumable and they are consistent with other related studies. These devices are particularly useful in patients with abnormalities of chest wall such as dermal carcinoma and tumor shell in patients with breast cancer (tumour the bottom shell). And also when there are open wounds in the chest area, such as tracheotomy or fibrosis caused by radiation therapy, or in the presence of scars of flaps after surgery in head and neck cancer (or when it is expected that the patient will receive this surgery), severe kyphosis, obese patients and patients with respiratory failure.

Mecanismo de acción y desarrollo preclínico de afatinib / Mechanism of action and preclinical development of afatinib

Afatinib, junto con gefitinib y erlotinib, está aprobado para el tratamiento de primera línea del cáncer de pulmón de célula no pequeña avanzado con mutaciones activadoras del receptor del factor de crecimiento epidérmico (EGFR). Se trata de un inhibidor irreversible de la familia ErbB, que actúa sobre EGFR (HER1, ErbB1), ErbB2 (HER2) y ErbB4 (HER4). Su unión covalente a los residuos de cisteína en el dominio catalítico de EGFR, HER2 y ErbB4, inhibe la actividad tirosincinasa (ITK) de estos receptores, disminuyendo la auto y la transfosforilación entre los dímeros ErbB y bloqueando, por tanto, la actividad de diferentes vías de señalización intracelular relacionadas con el crecimiento y la supresión de la apoptosis celular. En los modelos preclínicos, esto se ha traducido en una reducción del tamaño tumoral. Además se sugiere que por su mecanismo de acción podría ser más potente que los EGFR ITK de primera generación (gefitinib y erlotinib) e incluso podría ser capaz de revertir la resistencia adquirida a dichos tratamientos. Por último, el sinergismo demostrado con otros agentes diana y quimioterápicos lo convierten en un fármaco de interés para potenciar su desarrollo clínico en combinación (AU)

Afatinib, together with gefitinib and erlotinib, is approved for first-line treatment of advanced non-small cell lung cancer (NSCLC) with activating mutations of the epidermal growth factor receptor (EGFR). This is an irreversible inhibitor of the ErbB family, acting on EGFR (HER1, ErbB1), ErbB2 (HER2) and ErbB4 (HER4). Covalent attachment to cysteine residues in the catalytic domain of EGFR, HER2 and ErbB4 inhibits the tyrosine kinase activity (TKIs) of these receptors, decreasing auto- and transphosphorylation between ErbB dimers, and thus blocking the activity of downstream signalling pathways related to growth and apoptosis suppression. In preclinical models, this has resulted in a reduction in tumour size. Furthermore, due to its mechanism of action, afatinib may be more potent than the first-generation EGFR TKIs (gefitinib and erlotinib) and may even be able to overcome acquired resistance to such treatments. Finally, because of the demonstrated synergism with other chemotherapeutic and target agents, it could be interesting to enhance its clinical development in combination with other drugs (AU)

Different exosome cargo from plasma/bronchoalveolar lavage in non-small-cell lung cancer.

Tumor-derived exosomes mediate tumorigenesis by facilitating tumor growth, metastasis, development of drug resistance, and immunosuppression. However, little is known about the exosomes isolated from bronchoalveolar lavage (BAL) in patients with lung neoplasm. Exosomes isolated in plasma and BAL from 30 and 75 patients with tumor and nontumor pathology were quantified by acetylcholinesterase activity and characterized by Western Blot, Electron Microscopy, and Nanoparticle Tracking Analysis. Differences in exosome cargo were analyzed by miRNA quantitative PCR in pooled samples and validated in a second series of patients. More exosomes were detected in plasma than in BAL in both groups (P < 0.001). The most miRNAs evaluated by PCR array were detected in tumor plasma, tumor BAL, and nontumor BAL pools, but only 56% were detected in the nontumor plasma pool. Comparing the top miRNAs with the highest levels detected in each pool, we found close homology only between the BAL samples of the two pathologies. In tumor plasma, we found a higher percentage of miRNAs with increased levels than in tumor BAL or in nontumor plasma. The data reveal differences between BAL and plasma exosome amount and miRNA content.

The role of anthracyclines in small cell lung cancer.

Small cell lung cancer (SCLC) represents the 15% of the totally of lung cancer. The percentage of cases in women is arising due to the differences in smoking patterns; it occurs almost exclusively in smokers and appears to be most common in heavy smokers. The stage of disease at presentation is the most important prognostic factor in patients with SCLC; for patients with extended stage disease, the median survival is around 10 months, and the five-year survival rate is 1 to 2 percent. The standard regimen for patients with extensive disease is cisplatin based chemotherapy. Second line chemotherapy is generally less effective than the initial treatment but it can provide significant palliation for many patients. We make a review here of the different options of second line chemotherapy and the role of anthracyclines in it.

Prevalencia de síntomas neuropsiquiátricos en pacientes institucionalizados con diagnóstico de demencia y factores asociados: estudio transversal multicéntrico / Prevalence of neuropsychiatric symptoms and associated factors in institutionalised dementia patients: a multicentre cross-sectional study

Objetivo. El objetivo fue estimar la prevalencia y la gravedad de los síntomas neuropsiquiátricos en los pacientes con demencia ingresados en centros residenciales, evaluando su asociación con ciertos factores que podrían influir en su aparición. Material y métodos. Se realizó un estudio transversal. Se incluyeron todos los ancianos diagnosticados de demencia degenerativa, vascular o mixta, en estadios 4 a 7 de la Global Deterioration Scale de Reisberg (GDS), y residentes en 6 centros residenciales de la provincia de Ourense (España). Se calculó un tamaño de muestra de 120 individuos. La evaluación de los síntomas se realizó utilizando el Neuropsychiatric Inventory-Nursing Home (NPI-NH). La influencia de los factores considerados se analizó mediante el análisis de regresión lineal y logística. Resultados. Fueron incluidos 212 casos con una media de edad de 85,7 (6,7) años. La prevalencia de síntomas neuropsiquiátricos fue 84,4%. El síntoma más común fue la apatía, seguido por la agitación y el delirio; los menos frecuentes fueron la euforia y las alucinaciones. El síntoma que producía más interrupción ocupacional fue la agitación. El análisis multivariante mostró que una mayor puntuación en el NPI-NH estaba asociada con mayor puntuación en la escala GDS y el uso de neurolépticos, inhibidores de la colinesterasa y memantina. Conclusiones. En los pacientes con demencia institucionalizados los síntomas neuropsiquiátricos que presentan prevalencia elevada se asociaban con la gravedad de la demencia GDS, el uso de neurolépticos, inhibidores de la colinesterasa y memantina(AU)

Objective. The aim was to estimate the prevalence and severity of neuropsychiatric symptoms in patients with dementia in nursing homes, assessing their association with certain factors that may influence their occurrence. Material and methods. A cross-sectional study was carried out, and included all elderly patients diagnosed with degenerative, vascular, or mixed dementia, stage 4 to 7 on the Global Deterioration Scale of Reisberg (GDS), and residents in 6 nursing homes in the province of Ourense (Spain). A sample size of 120 individuals was determined to be necessary. The assessment of symptoms was performed using the Neuropsychiatric Inventory-Nursing Home test. The influence of the determined factors was investigated using logistic and linear regression analysis, and subsequently corrected for possible confounding factors. Results. A total of 212 cases were included, with a mean age of 85.7 (SD=6.7) years. The prevalence of neuropsychiatric symptoms was 84.4%. The most common symptom was apathy, followed by agitation and delirium, and the least frequent were euphoria and hallucinations. The symptom that produced most occupational disruption was agitation. Multivariate analysis showed that a higher score on the NPI-NH was associated with a higher score on the Global Deterioration Scale of Reisberg, the use of neuroleptics, cholinesterase inhibitors, and memantine. Conclusions. In nursing home patients, prevalence of neuropsychiatric symptoms was high, and associated with the severity of dementia (GDS), the use of neuroleptics, cholinesterase inhibitors, and memantine(AU)