Adherence to protective mechanical ventilation in COVID-19 versus non-COVID-19-associated acute respiratory distress syndrome: Comparison between two prospective cohorts / Adhesión a la ventilación mecánica protectora en el síndrome de dificultad respiratoria aguda asociado a COVID-19 o asociado a otras etiologias: comparación entre dos cohortes prospectivas

Objective To compare adherence to protective mechanical ventilation (MV) parametersin patients with acute respiratory distress syndrome (ARDS) caused by COVID-19 with patients with ARDS from other etiologies. Design Multiple prospective cohort study. Setting: Two Brazilian cohorts of ARDS patients were evaluated. One with COVID-19 patients admitted to two Brazilian intensive care units (ICUs) in 2020 and 2021 (C-ARDS, n=282), the other with ARDS-patients from other etiologies admitted to 37 Brazilian ICUs in 2016 (NC-ARDS, n=120). Patients: ARDS patients under MV. Interventions: None. Main variables of interest: Adherence to protective MV (tidal volume ≤8mL/kg PBW; plateau pressure ≤30cmH2O; and driving pressure ≤15cmH2O), adherence to each individual component of the protective MV, and the association between protective MV and mortality. Results Adherence to protective MV was higher in C-ARDS than in NC-ARDS patients (65.8% vs. 50.0%, p=0.005), mainly due to a higher adherence to driving pressure ≤15cmH2O (75.0% vs. 62.4%, p=0.02). Multivariable logistic regression showed that the C-ARDS cohort was independently associated with adherence to protective MV. Among the components of the protective MV, only limiting driving pressure was independently associated with lower ICU mortality. Conclusions Higher adherence to protective MV in patients with C-ARDS was secondary to higher adherence to limiting driving pressure. Additionally, lower driving pressure was independently associated with lower ICU mortality, which suggests that limiting exposure to driving pressure may improve survival in these patients (AU)

Objetivo Comparar la adhesión a la ventilación mecánica (VM) protectora en pacientes con síndrome de dificultad respiratoria aguda (SDRA) causada por COVID-19 con pacientes con SDRA de otras etiologías. Diseño Estudio de cohorte prospectivo. Âmbito: Se evaluaron dos cohortes de pacientes con SDRA: 1.pacientes con COVID-19 ingresados en dos unidades de cuidados intensivos (UCI) brasileñas en 2020 y 2021 (C-ARDS, n=282); 2.pacientes con SDRA de otras etiologías ingresados en 37 UCI brasileñas en 2016 (NC-ARDS, n=120). Pacientes: Pacientes con SDRA bajo VM invasiva. Intervenciones: No. Variables de interés principals: Adhesión a la VM protectora (volumen tidal ≤8mL/kg; presión de meseta ≤30cmH2O; y presión de distensión [PD] ≤15cmH2O), adhesión a cada componente individual de la VM protectora, y la asociación entre la VM protectora y la mortalidad. Resultados La adhesión a la VM protectora fue mayor en la cohorte C-ARDS que en la NC-ARDS (65,8% vs. 50,0%, p=0,005), principalmente debido a mayor adhesión a la PD≤15cmH2O (75,0% vs. 62,4%, p=0,02). La regresión logística multivariable mostró que la cohorte C-ARDS se asoció de forma independiente con la adhesión a la VM protectora. Entre los componentes de la VM protectora, sólo la limitación de la PD se asoció de forma independiente con menor mortalidad en la UCI. Conclusión La mayor adhesión a la VM protectora en los pacientes con C-ARDS fue secundaria a la mayor adhesión a limitación da PD. Además, una menor PD se asoció de forma independiente a menor mortalidad en la UCI, lo que sugiere que limitar la exposición a altas PD puede mejorar la supervivencia en estos pacientes (AU)

Impacts of a fraction of inspired oxygen adjustment protocol in COVID-19 patients under mechanical ventilation: A prospective cohort study / Impactos de un protocolo de ajuste de la fracción de oxígeno inspirado en pacientes con COVID-19 sometidos a ventilación mecánica: un estudio de cohorte prospectivo

Objective We examined weather a protocol for fraction of inspired oxygen (FiO2) adjustment can reduce hyperoxemia and excess oxygen use in COVID-19 patients mechanically ventilated. Design Prospective cohort study. Settin Two intensive care units (ICUs) dedicated to COVID-19 patients in Brazil. Patients Consecutive patients with COVID-19 mechanically ventilated. Interventions One ICU followed a FiO2 adjustment protocol based on SpO2 (conservative-oxygen ICU) and the other, which did not follow the protocol, constituted the control ICU. Main variables of interest Prevalence of hyperoxemia (PaO2>100mmHg) on day 1, sustained hyperoxemia (present on days 1 and 2), and excess oxygen use (FiO2>0.6 in patients with hyperoxemia) were compared between the two ICUs. Results Eighty two patients from the conservative-oxygen ICU and 145 from the control ICU were included. The conservative-oxygen ICU presented lower prevalence of hyperoxemia on day 1 (40.2% vs. 75.9%, p<0.001) and of sustained hyperoxemia (12.2% vs. 49.6%, p<0.001). Excess oxygen use was less frequent in the conservative-oxygen ICU on day 1 (18.3% vs. 52.4%, p<0.001). Being admitted in the control ICU was independently associated with hyperoxemia and excess oxygen use. Multivariable analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FiO2 use and adverse clinical outcomes. Conclusions Following FiO2 protocol was associated with lower hyperoxemia and less excess oxygen use. Although those results were not associated with better clinical outcomes, adopting FiO2 protocol may be useful in a scenario of depleted oxygen resources, as was seen during the COVID-19 pandemic (AU)

Objetivo Evaluar si un protocolo para el ajuste de la FiO2 reduce la hiperoxemia y el uso excesivo de oxígeno en pacientes con COVID-19 en ventilación mecánica. Diseño Estudio de cohorte prospectivo. Ámbito Unidades de cuidados intensivos (UCI) dedicadas a pacientes con COVID-19 en Brasil. Pacientes Pacientes con COVID-19. Intervenciones Una UCI siguió un protocolo de ajuste de FiO2 basado en SpO2 (UCI de oxigenoterapia conservadora, N=82) y la otra no siguió el protocolo (UCI control, N=145). Principales variables de interés Prevalencia de hiperoxemia (PaO2>100mmHg) en el día 1, hiperoxemia sostenida (presente en los días 1 y 2) y exceso de uso de oxígeno (FiO2>0,6 en pacientes con hiperoxemia) entre las 2 UCI. Resultados La UCI de oxigenoterapia conservadora presentó menor prevalencia de hiperoxemia en el día 1 (40,2 vs. 75,9%; p<0,001) y de hiperoxemia sostenida (12,2 vs. 49,6%; p<0,001). El uso excesivo de oxígeno fue menos frecuente en la UCI de oxigenoterapia conservadora el día 1 (18,3 vs. 52,4%; p<0,001). El ingreso en la UCI control se asoció de forma independiente con la hiperoxemia y el uso excesivo de oxígeno. Los análisis multivariables no encontraron una relación independiente entre hiperoxemia o uso excesivo de FiO2 y resultados clínicos adversos. Conclusiones Seguir el protocolo de FiO2 se asoció con menor hiperoxemia y menor consumo de oxígeno en exceso. Aunque esos resultados no se asociaron con mejores resultados clínicos, la adopción del protocolo FiO2 puede ser útil en un escenario de recursos de oxígeno agotados, como se vio durante la pandemia de COVID-19 (AU)

Adherence to protective mechanical ventilation in COVID-19 versus non-COVID-19-associated acute respiratory distress syndrome: Comparison between two prospective cohorts.

OBJECTIVE: To compare adherence to protective mechanical ventilation (MV) parameters in patients with acute respiratory distress syndrome (ARDS) caused by COVID-19 with patients with ARDS from other etiologies. DESIGN: Multiple prospective cohort study. SETTING: Two Brazilian cohorts of ARDS patients were evaluated. One with COVID-19 patients admitted to two Brazilian intensive care units (ICUs) in 2020 and 2021 (C-ARDS, n=282), the other with ARDS-patients from other etiologies admitted to 37 Brazilian ICUs in 2016 (NC-ARDS, n=120). PATIENTS: ARDS patients under MV. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Adherence to protective MV (tidal volume ≤8mL/kg PBW; plateau pressure ≤30cmH2O; and driving pressure ≤15cmH2O), adherence to each individual component of the protective MV, and the association between protective MV and mortality. RESULTS: Adherence to protective MV was higher in C-ARDS than in NC-ARDS patients (65.8% vs. 50.0%, p=0.005), mainly due to a higher adherence to driving pressure ≤15cmH2O (75.0% vs. 62.4%, p=0.02). Multivariable logistic regression showed that the C-ARDS cohort was independently associated with adherence to protective MV. Among the components of the protective MV, only limiting driving pressure was independently associated with lower ICU mortality. CONCLUSIONS: Higher adherence to protective MV in patients with C-ARDS was secondary to higher adherence to limiting driving pressure. Additionally, lower driving pressure was independently associated with lower ICU mortality, which suggests that limiting exposure to driving pressure may improve survival in these patients.

Impacts of a fraction of inspired oxygen adjustment protocol in COVID-19 patients under mechanical ventilation: A prospective cohort study.

Objective: We examined weather a protocol for fraction of inspired oxygen (FiO2) adjustment can reduce hyperoxemia and excess oxygen use in COVID-19 patients mechanically ventilated. Design: Prospective cohort study. Setting: Two intensive care units (ICUs) dedicated to COVID-19 patients in Brazil. Patients: Consecutive patients with COVID-19 mechanically ventilated. Interventions: One ICU followed a FiO2 adjustment protocol based on SpO2 (conservative-oxygen ICU) and the other, which did not follow the protocol, constituted the control ICU. Main variables of interest: Prevalence of hyperoxemia (PaO2 >100 mmHg) on day 1, sustained hyperoxemia (present on days 1 and 2), and excess oxygen use (FiO2 > 0.6 in patients with hyperoxemia) were compared between the two ICUs. Results: Eighty two patients from the conservative-oxygen ICU and 145 from the control ICU were included. The conservative-oxygen ICU presented lower prevalence of hyperoxemia on day 1 (40.2% vs. 75.9%, p < 0.001) and of sustained hyperoxemia (12.2% vs. 49.6%, p < 0.001). Excess oxygen use was less frequent in the conservative-oxygen ICU on day 1 (18.3% vs. 52.4%, p < 0.001). Being admitted in the control ICU was independently associated with hyperoxemia and excess oxygen use. Multivariable analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FiO2 use and adverse clinical outcomes. Conclusions: Following FiO2 protocol was associated with lower hyperoxemia and less excess oxygen use. Although those results were not associated with better clinical outcomes, adopting FiO2 protocol may be useful in a scenario of depleted oxygen resources, as was seen during the COVID-19 pandemic.

Objetivo: Evaluar si un protocolo para el ajuste de la FiO2 reduce la hiperoxemia y el uso excesivo de oxígeno en pacientes con COVID-19 en ventilación mecánica. Diseño: Estudio de cohorte prospectivo. Ámbito: Unidades de cuidados intensivos (UCI) dedicadas a pacientes con COVID-19 en Brasil. Pacientes: Pacientes con COVID-19. Intervenciones: Una UCI siguió un protocolo de ajuste de FiO2 basado en SpO2 (UCI de oxigenoterapia conservadora, N = 82) y la otra no siguió el protocolo (UCI control, N = 145). Principales variables de interés: Prevalencia de hiperoxemia (PaO2 > 100 mmHg) en el día 1, hiperoxemia sostenida (presente en los días 1 y 2) y exceso de uso de oxígeno (FiO2 > 0,6 en pacientes con hiperoxemia) entre las 2 UCI. Resultados: La UCI de oxigenoterapia conservadora presentó menor prevalencia de hiperoxemia en el día 1 (40,2 vs. 75,9%; p < 0,001) y de hiperoxemia sostenida (12,2 vs. 49,6%; p < 0,001). El uso excesivo de oxígeno fue menos frecuente en la UCI de oxigenoterapia conservadora el día 1 (18,3 vs. 52,4%; p < 0,001). El ingreso en la UCI control se asoció de forma independiente con la hiperoxemia y el uso excesivo de oxígeno. Los análisis multivariables no encontraron una relación independiente entre hiperoxemia o uso excesivo de FiO2 y resultados clínicos adversos. Conclusiones: Seguir el protocolo de FiO2 se asoció con menor hiperoxemia y menor consumo de oxígeno en exceso. Aunque esos resultados no se asociaron con mejores resultados clínicos, la adopción del protocolo FiO2 puede ser útil en un escenario de recursos de oxígeno agotados, como se vio durante la pandemia de COVID-19.

Impacts of a fraction of inspired oxygen adjustment protocol in COVID-19 patients under mechanical ventilation: A prospective cohort study.

OBJECTIVE: We examined weather a protocol for fraction of inspired oxygen (FiO2) adjustment can reduce hyperoxemia and excess oxygen use in COVID-19 patients mechanically ventilated. DESIGN: Prospective cohort study. SETTING: Two intensive care units (ICUs) dedicated to COVID-19 patients in Brazil. PATIENTS: Consecutive patients with COVID-19 mechanically ventilated. INTERVENTIONS: One ICU followed a FiO2 adjustment protocol based on SpO2 (conservative-oxygen ICU) and the other, which did not follow the protocol, constituted the control ICU. MAIN VARIABLES OF INTEREST: Prevalence of hyperoxemia (PaO2>100mmHg) on day 1, sustained hyperoxemia (present on days 1 and 2), and excess oxygen use (FiO2>0.6 in patients with hyperoxemia) were compared between the two ICUs. RESULTS: Eighty two patients from the conservative-oxygen ICU and 145 from the control ICU were included. The conservative-oxygen ICU presented lower prevalence of hyperoxemia on day 1 (40.2% vs. 75.9%, p<0.001) and of sustained hyperoxemia (12.2% vs. 49.6%, p<0.001). Excess oxygen use was less frequent in the conservative-oxygen ICU on day 1 (18.3% vs. 52.4%, p<0.001). Being admitted in the control ICU was independently associated with hyperoxemia and excess oxygen use. Multivariable analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FiO2 use and adverse clinical outcomes. CONCLUSIONS: Following FiO2 protocol was associated with lower hyperoxemia and less excess oxygen use. Although those results were not associated with better clinical outcomes, adopting FiO2 protocol may be useful in a scenario of depleted oxygen resources, as was seen during the COVID-19 pandemic.

Preferential habitats prediction in syngnathids using species distribution models.

Syngnathids are considered as flagship species for marine conservation. Seahorses and pipefish are highly vulnerable to anthropogenic and environmental disturbances, but most species are currently considered Data Deficient by IUCN, requiring more biological and ecological research. Although syngnathids are well known for their unusual breeding biology, some aspects on the ecology of this family have rarely received attention. The knowledge on the factors governing syngnathids distribution is limited to some species and geographical regions. The present study is the first approach to predict syngnathid habitat preference in Spanish coasts, particularly in a marine National Park. In this study, Species Distribution Models (SDMs) were implemented to investigate the preferential habitat and distribution of the pipefish Syngnathus acus in Cíes Archipelago (Atlantic Islands of Galicia National Park, PNIA). Occurrence data of the species obtained from 2016 to 2018 surveys in PNIA were modeled as a function of bathymetric (depth, slope), substrate (sediment texture) and oceanographic (waves exposure) variables, using GAM, Random Forest and Maxent algorithms. From those SDMs, prediction models were built and the ensemble map of predictions was performed. The variables that most determined the distribution of the species were depth and wave exposure. The results of this study provide information on (1) habitat preference in the most dominant species in PNIA, the pipefish S. acus, towards sustainable management of this species in the National Park, and (2) predictive statistical tools for proper spatial conservation plans of this syngnathid species.

First-line panitumumab plus docetaxel and cisplatin in advanced gastric and gastro-oesophageal junction adenocarcinoma: results of a phase II trial.

PURPOSE: Panitumumab is extensively used for RAS-WT metastatic colorectal cancer. This study assessed the efficacy and safety of panitumumab plus first-line chemotherapy [docetaxel (DOC) and cisplatin (CIS)] in treatment-naïve advanced gastric or gastro-oesophageal junction (GEJ) adenocarcinoma (ADC) patients. METHODS: Phase II, open-label, single-arm study includes treatment-naïve advanced gastric or GEJ-ADC patients from ten Spanish centres. Patients received panitumumab (6 mg/kg) plus DOC and CIS (50 mg/m2 both) every 2 weeks until disease progression, unacceptable toxicity, or patient withdrawal. Primary endpoint: objective response rate (ORR); main secondary endpoints: disease control rate (DCR), duration of response (DoR), time to progressive disease (TTP), progression-free-survival (PFS), overall survival (OS), and safety. RESULTS: Forty-four patients were included; median age: 67.8 (range 43.3-82.7) years, 68.2% male. The ORR was 27.3% (95% CI 15.0, 42.8); median PFS and OS: 5.0 (95% CI 3.6, 6.9) and 7.2 (5.5, 9.0) months, respectively. Median TTP, DCR and DoR: 5.3 (range 3.8-7.0) months, 70.5% (95% CI 54.8, 83.2%), and 4.8 (1.8, NE) months. Median panitumumab treatment duration: 11.9 (range 0.1-34.9) weeks; 25.0% patients had a dose reduction and 40.9% discontinued treatment. Grade 3-4 adverse events (AEs): 68.2%/22.2% patients. Most common AEs: asthenia (75.0%) and mucosal inflammation (54.5%). Serious AEs were experienced by 54.6% patients; 9.1%, 13.6%, and 15.9% related to panitumumab, DOC, and CIS, respectively. Three (6.8%) patients died due to AEs not related to study treatment. CONCLUSIONS: The addition of panitumumab to standard chemotherapy as the first-line treatment in advanced gastric or GEJ-ADC does not appear to improve the efficacy outcomes.

Correction to: Phase II study to evaluate the efficacy of Trastuzumab in combination with Capecitabine and Oxaliplatin in first-line treatment of HER2-positive advanced gastric cancer: HERXO trial.

Phase II study to evaluate the efficacy of Trastuzumab in combination with Capecitabine.

First-line single-agent regorafenib in frail patients with metastatic colorectal cancer: a pilot phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD).

BACKGROUND: Treatment of frail patients with advanced colorectal cancer (CRC) is controversial. This pilot phase II trial aimed to assess the efficacy and safety of regorafenib when administered in first-line to frail patients with advanced CRC. METHODS: Frail patients without prior advanced colorectal cancer treatment were included in the study. Definition of frailty was defined per protocol based on dependency criteria, presence of chronic comorbid pathologies and/or geriatric features. MAIN OBJECTIVE: to assess progression-free survival (PFS) rate at 6 months. Treatment consisted of 28-day cycles of orally administered regorafenib 160 mg/day (3 weeks followed by 1 week rest). RESULTS: Forty-seven patients were included in the study. Median age was 81 years (range 63-89). Frailty criteria: dependency was observed in 26 patients (55%), comorbidities in 27 (57%) and geriatric features in 18 (38%). PFS rate at 6 months was 45% (95% confidence interval [CI] 30-60]. Median PFS was 5.6 months (95%CI 2.7-8.4). Median overall survival (OS) was 16 months (95%CI 7.8-24). Complete response, partial response and stable disease were observed in one, two and 21 patients respectively (objective response rate 6.4%; disease control rate 51%). Thirty-nine patients (83%) experienced grade 3-4 adverse events (AEs). The most common grade 3-4 AEs were hypertension (15 patients; 32%), asthenia (14; 30%), hypophosphatemia (6; 13%); diarrhea (4; 8%), hand-foot-skin reaction (4; 8%). There were two toxic deaths (4.2%) (grade 5 rectal bleeding and death not further specified). Dose reduction was required in 26 patients (55%) and dose-delays in 13 patients (28%). CONCLUSIONS: The study did not meet the pre-specified boundary of 55% PFS rate at 6 months. Toxicity observed (83% patients experienced grade 3 and 4 AEs) preclude its current use in clinical practice on this setting. Disease control rate and overall survival results are interesting and might warrant further investigation to identify those who benefit from this approach. TRIAL REGISTRATION: This trial was prospectively registered at EudraCT ( 2013-000236-94 ). Date of trial registration: April 9th, 2013.

Phase II study to evaluate the efficacy of Trastuzumab in combination with Capecitabine and Oxaliplatin in first-line treatment of HER2-positive advanced gastric cancer: HERXO trial.

PURPOSE: The phase III ToGA trial established cisplatin, fluoropyrimidine and trastuzumab as the standard treatment in HER2-positive advanced gastric cancer (AGC). However, as demonstrated in HER2-negative AGC, oxaliplatin-based regimens could improve tolerance remaining effective. The aim of this trial was to explore the potential activity and safety of capecitabine, oxaliplatin (XELOX) and trastuzumab in patients with HER-2 positive advanced gastric cancer. METHODS: We conducted a multicentre, prospective, non-randomised, non-controlled, open-label and national (Spanish) phase II study. Patients with HER2-positive advanced gastric or gastro-oesophageal junction (EGJ) cancer received XELOX and trastuzumab as first-line treatment. Primary endpoint was objective tumour response rate (ORR). RESULTS: 45 patients from ten hospitals in Spain were included from September 2011 to December 2013. Median age was 65 years, 82.2% were male, 69% had gastric cancer and 31% had EGJ tumours. At a median follow-up of 13.7 months (7.1-20.9), the estimated median progression-free survival and overall survival were 7.1 (95% CI 5.5-8.7) and 13.8 months (95% CI 10.1-17.4), respectively, with 8.9%, 37.8% and 31.1% of patients achieving complete response, partial response and stable disease. Regarding safety, 44.4% of the patients had grade 3 or greater adverse events, being the most frequent diarrhoea (26.6%), fatigue (15.5%), nausea (20%) and vomiting (13.3%). Only two patients (4.4%) developed asymptomatic grade 2 left ventricle ejection fraction reduction. CONCLUSIONS: XELOX-trastuzumab is a promising and effective therapy as first-line treatment for patients with HER2-positive AGC, with comparable results to the ones obtained with other "platinum-based" regimens. This scheme is feasible and tolerable with a low incidence of cardiac toxicity.

First-line mFOLFOX plus cetuximab followed by mFOLFOX plus cetuximab or single-agent cetuximab as maintenance therapy in patients with metastatic colorectal cancer: Phase II randomised MACRO2 TTD study.

BACKGROUND: This multicentre, randomised, and phase II study evaluated mFOLFOX+cetuximab followed by maintenance mFOLFOX+cetuximab or single-agent cetuximab in metastatic colorectal cancer (mCRC) patients (NCT01161316). PATIENTS AND METHODS: Previously, untreated mCRC patients (wild-type KRAS) were randomised to receive cetuximab+mFOLFOX-6 (8 cycles for 2 weeks) followed by maintenance therapy: single-agent cetuximab (Arm-A) or mFOLFOX-6 + cetuximab (Arm-B) until progression. Primary endpoint was progression-free survival (PFS) at 9 months. RESULTS: One hundred ninety-three patients (median [range] age 60 [33-74] years) were randomised (2:1): 129 Arm-A versus 64 Arm-B. PFS at 9 months (95% confidence interval) showed non-inferiority between arms (Arm-A/Arm-B: 60 [52, 69]%/72 [61, 83]%, p [non-inferiority]<0.1). There were no statistically significant differences in the PFS (Arm-A/Arm-B: 9 [95% CI 7, 10] months/10 [7,13] months, hazard ratio [HR] = 1.19 [0.80, 1.79]) or overall survival (23 [19, 28] months/27 [18, 36] months, HR = 1.24 [0.85, 1.79]) between arms. The objective response rate was also similar (48 [39, 57]%/39 [27, 52]%). The safety profile was similar between arms, and all patients experienced at least one adverse event (AE) (Arm-A/Arm-B grade ≥III AEs: 70%/68%). The most common grade ≥III AEs were as follows: neutropenia (Arm-A/Arm-B: 28%/26%), rash acneiform (15%/24%) and sensory neuropathy (2%/15%) in any group. Arm-A was associated with less grade ≥III rash and sensory neuropathy and a lower rate of serious AEs (20%/27%). CONCLUSION(S): This phase II exploratory trial with a non-inferiority design suggests that maintenance therapy with single-agent cetuximab following mFOLFOX+cetuximab induction could be a valuable option compared with mFOLFOX+cetuximab treatment continuation. We await phase III trials to confirm single-agent cetuximab as maintenance therapy in mCRC patients.

Correction to: Fraction of high-grade cervical intraepithelial lesions attributable to genotypes targeted by a nonavalent HPV vaccine in Galicia, Spain.

After publication of the article [1], it was brought to our attention that the author E. López-Díez is missing their second affiliation. The author would also like to indicate an affiliation to "Universidade de Vigo, Pontevedra, Spain".

Fraction of high-grade cervical intraepithelial lesions attributable to genotypes targeted by a nonavalent HPV vaccine in Galicia, Spain.

BACKGROUND: Human papillomavirus (HPV) bivalent and quadrivalent vaccines have been widely implemented in worldwide organized immunization programs. A nonavalent HPV vaccine is now available in several countries. The objective was to describe the fraction of squamous non-invasive high-grade cervical intraepithelial lesions attributable to genotypes targeted by bi-quadrivalent vaccines and by nonavalent vaccine according to age and diagnosis in women living in the city of Vigo (Galicia, Spain). METHODS: Cervical scrapings (2009-2014) of women with histological diagnosis of cervical intraepithelial neoplasia grade 2 (CIN2, n = 145) and grade 3-carcinoma in situ (CIN3-CIS, n = 244) were tested with Linear Array HPV Genotyping test (Roche diagnostics, Mannheim, Germany). Hierarchical estimation of the fraction attributable to HPV 16/18 or HPV 31/33/45/52/58 detected alone or in combination was calculated. Absolute additional fraction attributable to genotypes targeted by nonavalent vaccine compared to genotypes targeted by bi-quadrivalent vaccines was calculated as the increment of attributable cases with respect to all studied cases. Age group 1, 2 and 3 included women 18 to 34, 35-44 and ≥45 years old, respectively. EPIDAT 3.1 was used. RESULTS: Fraction attributable to genotypes targeted by bi-quadrivalent vaccines was 59% CIN2 vs. 69% CIN3-CIS (p < 0.001). It was 63/51/50% of CIN2 and 78/66/45% of CIN3-CIS in age group 1, 2, 3, respectively. Fraction attributable to genotypes targeted by nonavalent vaccine was 86% CIN2 and 86% CIN3-CIS. It was 87/91/75% of CIN2 and 90/86/76% of CIN3-CIS in age group 1, 2, 3, respectively. Fraction attributable to genotypes targeted by these vaccines tended to decrease as age increased (p-trend <0.05). Globally, absolute additional attributable fraction was 16%, 26% and 29% in age group 1, 2 and 3, respectively (p < 0.005). CONCLUSIONS: Absolute additional fraction of CIN2 and CIN3-CIS attributable to genotypes targeted by nonavalent vaccine was observed in women of any age, especially in those over 35 years old.

First-line single-agent panitumumab in frail elderly patients with wild-type KRAS metastatic colorectal cancer and poor prognostic factors: A phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours.

BACKGROUND: Frail elderly patients with metastatic colorectal cancer (mCRC) are not candidates for chemotherapy. Monotherapy with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies may be an option for these patients with few systemic toxic effects. PATIENTS AND METHODS: Single-arm, multicentre, phase II trial including patients ⩾ 70y ears with wild-type (WT) KRAS (exon 2) mCRC, Eastern Cooperative Oncology Group (ECOG) status ⩽ 3, KPC (Köhne Prognostic Classification)--defined intermediate or high risk status, frailty and/or ineligibility for chemotherapy. Patients received panitumumab until progression or unacceptable toxicity. The primary end-point was progression free survival (PFS) rate at 6 months. RESULTS: The study included 33 patients (intention-to-treat (ITT) population). Median age: 81 years; sex: 66.7% male; high-risk KPC status: 45.4%. Median treatment duration was 14 weeks and 6-month PFS rate was 36.4% (95% confidence interval (CI): 20.0-52.8). The objective response rate: 9.1% (95% CI: 0-18.9) (all partial responses), and there were 18 stable diseases (54.5%). Median PFS was 4.3 months (95% CI: 2.8-6.4) and median overall survival (OS) was 7.1 months (95% CI: 5.0-12.3). There were no deaths or grade 4-5 adverse events (AEs) related to panitumumab and the most common grade 3-related AE was rash acneiform (15.2%). A significant association between clinical response and RAS status was observed (P=0.037). In the WT RAS subgroup (WT exons 2, 3, and 4 of KRAS and NRAS, N = 15), 6-month PFS rate was 53.3% (95% CI: 30.1-75.2) and median PFS and OS were 7.9 and 12.3 months, respectively. CONCLUSIONS: Single-agent panitumumab is active and well tolerated and may be a therapeutic option for high-risk frail elderly patients with WT RAS tumours considered not candidates for chemotherapy (clinicaltrials.gov identifier NCT01126112).

Phase II trial of miniDOX (reduced dose docetaxel-oxaliplatin-capecitabine) in "suboptimal" patients with advanced gastric cancer (AGC). TTD 08-02.

PURPOSE: Chemotherapy has improved the overall survival (OS) in patients (pts) with advanced gastric cancer (AGC). Docetaxel (D), oxaliplatin (O) and capecitabine (C) have shown interesting activity in this setting. We defined "suboptimal" pts as those with PS ECOG = 2, weight loss 10-25% and/or age ≥70 years. This population is usually underrepresented in AGC clinical trials. METHODS: We explored in 43 previously untreated "suboptimal" AGC pts the effect of "miniDOX" regimen (D: 40 mg/m(2) iv, day 1; O: 80 mg/m(2) iv, day 1; C: 625 mg/m(2) po bid, day 1 to day 21, every 21 days; after six courses, only C was maintained). Primary end point was response rate (RR), and secondary end points were adverse events (AE), progression-free survival (PFS) and overall survival (OS). RESULTS: Patients characteristics: PS ECOG = 2: 12 pts; weight loss 10-25%: 23 pts; median age 73.3 years (range 40-87; 28 pts were ≥70 years); 32 males; locally advanced: 8 pts/metastatic: 35 pts; primary site: gastric 32 pts/EGJ 11. Worst AE per pt (grade 3-4): neutropenia: 5 pts (febrile neutropenia: 3); pulmonary embolism (PE): 4 pts (3 of them suffered sudden death); diarrhea: 9 pts; paronychia: 2 pts; ictus: 1 pt; renal failure: 1 pt (this pt suffered infection/bacteriemia without neutropenia and died); hand-foot syndrome: 4 pts and asthenia: 5 pts. RESPONSE: CR: 1 pt, PR: 23 pts (RR: 56%), SD: 12 pts, progression: 3 pts, no determined: 4 pts. Median and 1 year actuarial PFS and OS were 5.5 months/18% and 13.3 months/52%, respectively. CONCLUSIONS: Although miniDOX's toxicity (mainly PE)has been important, its activity has been promising in "suboptimal" pts with AGC, and this combination should be further investigated in this setting.

Physical activity in daily life assessed by an accelerometer in kidney transplant recipients and hemodialysis patients.

BACKGROUND: Sedentary lifestyle is a problem among hemodialysis (HD) patients, potentially attenuated after kidney transplantation. However, the effect of kidney transplantation on physical activity has not been thoroughly investigated. OBJECTIVE: This study sought to evaluate the physical activity in daily life in kidney transplant recipients (KTRs) compared with HD patients and to explore its relationship with clinical variables. METHODS: A cross-sectional study enrolled KTRs who received transplants at least 6 months before the study (N = 23; 48.3 ± 10.3 years) and patients undergoing HD for at least 6 months (N = 20; 47.3 ± 12.6 years). Time spent in different activities (walking, standing, sitting, and lying down) and number of steps taken, measured by a multiaxial accelerometer used for 12 h/d on 2 consecutive days for KTRs and on 4 consecutive days for HD patients, were evaluated. RESULTS: KTRs engaged in more active time per day (sum of walking and standing time) than HD patients (311 ± 87 vs 196 ± 54 min/d; P = .001), with longer walking (106 ± 53 vs 70 ± 27 min/d; P = .008) and standing time (205 ± 55 vs 126 ± 42 min/d; P < .001). Sixty-five percent of KTRs were classified as active (>7500 steps/d) compared with only 20% of the HD group (P < .05). The multivariate analysis showed that time posttransplantation was significantly associated with walking time and active time. CONCLUSIONS: By using an accelerometer, a precise method, this study showed that KTRs are significantly more active in daily life than HD patients, and that daily physical activity increases with time since transplantation.

Dielectric behavior of epoxy/BaTiO3 composites using nanostructured ceramic fibers obtained by electrospinning.

Composite materials made of epoxy resin and barium titanate (BT) electrospun nanostructured fibers were prepared. BT fibers were synthesized from a sol based on barium acetate, titanium isopropoxide, and poly(vinyl pyrrolidone). The fibers were heat-treated at different temperatures and characterized by X-ray diffraction, scanning electron microscopy (SEM), and Raman spectroscopy. Mats of BT fibers heat-treated at 800 °C were embedded in epoxy resin into suitable molds. The composites were characterized by SEM, and dielectric measurements were performed by means of dielectric spectroscopy. The dielectric permittivity and dielectric modulus of epoxy resin/BT-fiber composites were measured for two types of samples: with the electrodes parallel and perpendicular to the BT fiber layers. Interestingly, composite samples with electrodes perpendicular to the fiber layers and a BT content as low as 2 vol % led to dielectric permittivities three times higher than that of pure epoxy resin.

Incidence of hand-foot syndrome with capecitabine in combination with chemotherapy as first-linetreatment in patients with advanced and/or metastatic gastric cancer suitable for treatment with a fluoropyrimidine-based regimen

INTRODUCTION: Hand-foot syndrome (HFS) is a limiting toxicity of capecitabine, which is not life-threatening but could compromise capecitabine efficacy. MATERIALS AND METHODS: This phase II, multicenter, non-controlled study assessed the safety, particularly grade three HFS incidence, and efficacy of four capecitabine-based chemotherapy regimens [cisplatin/capecitabine (CX), epirubicin/cisplatin/capecitabine (ECX), epirubicin/oxaliplatin/capecitabine (EOX) and docetaxel/cisplatin/capecitabine (DCX)] as first-line treatment for advanced and/or metastatic gastric cancer. RESULTS: One hundred and eight patients were assigned to one of the four treatment groups, according to investigator's criteria, and grouped together for both safety and efficacy primary analyses. HFS was reported in 31 patients (19.6%) and its first presentation occurred at a median of 72 days (range 19-209 days). Grade 3 HFS developed in 6.3, 5.2, 3.7 and 2.4%, of patients receiving ECX, DCX, EOX or CX chemotherapy regimen, respectively. Capecitabine dose reduction/discontinuation due to HFS was required in 5.7% of patients (9/158). The most common (> 10%) grade 3-4 treatment-related AEs were neutropenia (15.2%), asthenia (12.0%) and diarrhoea (11.4%). CONCLUSIONS: A moderate incidence of HFS was reported in patients treated with capecitabine, which generally presented late and required dose reduction in < 1/3 of patients. The results suggest that capecitabine may be useful in combination with standard fluorouracil-based regimens in patients with advanced and/or metastatic gastric cancer with favourable safety profile (AU)

A retrospective observational study on the safety and efficacy of first-line treatment with bevacizumab combined with FOLFIRI in metastatic colorectal cancer.

BACKGROUND: Combination of bevacizumab and FOLFIRI has currently become one of the standard therapeutic regimens. However, published information is still limited. The objective of the present retrospective observational study is to analyse the response and toxicity of first-line treatment with FOLFIRI+bevacizumab in patients with metastatic colorectal cancer (mCRC). METHODS: Data were collected from patients from nine Spanish sites diagnosed with mCRC, ECOG≤2, whose first treatment for advanced disease was at least three cycles of FOLFIRI+bevacizumab. RESULTS: A total of 95 patients were enrolled into the study: 64.2% males, median age of 59 years (53.2-67.1 years), ECOG=0-1 in 96.9% of patients. The main site of primary tumour was the colon (69.7%), and most metastases occurred in the liver (71.6%). Clinical benefit was detected in 67.4% (57.0-76.6; 95% confidence interval (CI)), with 8.4% of CR and 42.1% of PR. Median TTP was 10.6 months (10.0-11.3; 95% CI), PFS was 10.6 months (9.8-11.3; 95% CI), and OS was 20.7 months (17.1-24.2; 95% CI). Main grade I-II toxicities included haematological toxicity (35.8%), diarrhea (27.3%), mucositis (25.3%), asthenia (19.0%), haemorrhages (11.6%), and emesis (10.6%). Toxicities reaching grades III-IV were haematological toxicity (9.5%), diarrhea (8.5%), mucositis (5.3%), hepatic toxicity (2.1%), asthenia (2.1%), proteinuria (1.1%), emesis (1.1%), pain (1.1%), and colics (1.1%). CONCLUSION: Results of this study support the beneficial effect of adding bevacizumab to FOLFIRI regimen in terms of efficacy and show a favourable tolerability profile.

Locally advanced breast cancer: pulmonary toxicity secondary to gemcitabine

Gemcitabine is indicated for the treatment of nonmicrocytic lung, breast, pancreatic, bladder and ovarian cancer. Mild dyspnea has been reported but the incidence of severe lung damage is low. We report the case of a 58-year-old woman diagnosed with locally advanced infiltrating ductal carcinoma of the breast who received gemcitabine as part of neoadjuvant chemotherapy and suffered from severe pulmonary toxicity. We reviewed the cases published in the literature and conclude that although Gemcitabine is generally well tolerated, pulmonary toxicity requires high level of suspicion and prompt treatment to prevent an unfavourable outcome (AU)