Kinetics of Thermal Degradation of Cellulose: Analysis Based on Isothermal and Linear Heating Data

[Abstarct]: In spite of the many studies performed, there is not yet a kinetic model to predict the thermal degradation of cellulose in isothermal and non-isothermal conditions for the full extent of conversion. A model proposed by the authors was tested on non-oxidising thermogravimetric data. The method consisted of initially fitting several isothermal and non-isothermal curves, then obtaining a critical temperature and an energy barrier from the set of fittings that resulted from different experimental conditions. While the critical temperature, approximately 226 °C, represented the minimum temperature for the degradation process, the degradation rate at a given temperature was related to both the critical temperature and the energy barrier. These results were compared with those observed in other materials. The quality of fittings obtained was superior to any other reported to date, and the results obtained from each single curve were in line with each other.This work was partially funded by the Spanish Ministerio de Educación y Ciencia (MTM2011-22393 and MTM2014-52876-R

Preoperative exercise training prevents functional decline after lung resection surgery: a randomized, single-blind controlled trial

[Abstract] Objectives: To investigate the effects of a preoperative pulmonary rehabilitation programme in patients with lung cancer undergoing video-assisted thoracic surgery. Design: Randomized, single-blind controlled trial. Setting: Teaching hospital. Subjects: Patients with suspected or confirmed lung cancer undergoing video-assisted thoracic surgery. Intervention: Participants were randomized to either a prehabilitation group or a control group. Participants in the prehabilitation group underwent a combination of moderate endurance and resistance training plus breathing exercises three to five times per week. Main measures: The primary outcome of the study was exercise capacity. Secondary outcomes were muscle strength (Senior Fitness Test), health-related quality of life (Short-Form 36) and the postoperative outcomes. Patients were evaluated at baseline (before randomization), presurgery (only the prehabilitation group), after surgery and three months post-operatively. Results: A total of 40 patients were randomized and 22 finished the study (10 in the prehabilitation group and 12 in the control group). Three patients were lost to follow-up at three months. After the training, there was a statistically significant improvement in exercise tolerance (+397 seconds, p = 0.0001), the physical summary component of the SF-36 (+4.4 points, p = 0.008) and muscle strength (p < 0.01). There were no significant differences between groups after surgery. However, three months postoperatively, significant differences were found in the mean change of exercise capacity (p = 0.005), physical summary component (p = 0.001) and upper and lower body strength (p = 0.045 and p = 0.002). Conclusions: A pulmonary rehabilitation programme before video-assisted thoracic surgery seems to improve patients’ preoperative condition and may prevent functional decline after surger

Respiratory Physiotherapy in Post-COVID-19: A Decision-Making Algorithm for Clinical Practice

[Resumen] La pandemia causada por la enfermedad de la COVID-19 ha supuesto un gran reto para los profesionales del sistema sociosanitario, intensificándose con el manejo y atención de las manifestaciones clínicas que potencialmente pueden presentarse de manera persistente en las personas que han superado la enfermedad. Para ello, la fisioterapia respiratoria se presenta como piedra angular dentro del modelo de abordaje interdisciplinar que requiere esta población. Dado que la implementación de esta opción terapéutica continúa siendo limitada en España, es imprescindible realizar una evaluación integral y exhaustiva de la persona que nos permita establecer criterios de selección a fin de optimizar el uso de los recursos humanos y materiales existentes. Para ello, se propone un algoritmo de decisión terapéutica basado en pruebas de evaluación validadas y objetivas de las posibles manifestaciones clínicas del paciente. La aplicación de este algoritmo, en cualquier nivel asistencial (atención especializada y atención primaria/comunitaria) junto con la atención centrada en la persona, el impulso del uso de los espacios comunitarios verdes y azules de las ciudades y un adecuado uso de las tecnologías de la comunicación y la información, nos permitirá optimizar el modelo de atención de fisioterapia respiratoria en el contexto actual, marcado por la COVID-19.[Abstract] The outbreak of COVID-19 has posed a great challenge for the healthcare system which has been later aggravated by the need of managing clinical manifestations and potential sequelae in COVID-19 survivors. In this context, respiratory Physiotherapy emerges as a cornerstone in the interdisciplinary management warranted in this population. Given that the implementation and resources available for the interdisciplinary therapeutic interventions in Spain is scarce, it is essential to perform a comprehensive, exhaustive and personalised assessment. This will allow us to establish more accurate selection criteria in order to optimise the use of existing human and material resources. To this end, we propose here a decision-making algorithm for clinical practice to assess the clinical manifestations in people recovered from COVID-19 based on well-established, validated tests and assessment tools. This algorithm can be used at any clinical practice environment (primary care/community or hospital-based), combined with a patient-centered model and the use of community and e-Health resources and its application to improve the Physiotherapy care of these patients in the COVID-19 era

Peripheral Inflammatory Indexes Neutrophil/Lymphocyte Ratio (NLR) and Red Cell Distribution Width (RDW) as Prognostic Biomarkers in Advanced Solitary Fibrous Tumour (SFT) Treated with Pazopanib

Simple Summary Pazopanib treatment in advanced solitary fibrous tumour patients, assessed in the prospective GEIS-32 phase II clinical trial, has shown longer progression-free survival and overall survival versus chemotherapy treatment in control patients. In recent years, the interest in the prognostic and predictive value of different peripheral inflammatory indexes, such as neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and red cell distribution width, has been increased in sarcomas, showing significant results in different soft tissue sarcomas. However, they have not been previously analysed in solitary fibrous tumour (SFT) patients. These indexes were retrospectively analysed in the typical- and malignant-SFT cohorts treated with pazopanib of the GEIS-32 trial to evaluate their predictive or prognostic value. Pazopanib was assessed prospectively in the GEIS-32 phase II study (NCT02066285) on advanced solitary fibrous tumour (SFT), resulting in a longer progression-free survival (PFS) and overall survival (OS) compared with historical controls treated with chemotherapy. A retrospective analysis of peripheral inflammatory indexes in patients enrolled into GEIS-32 was performed to evaluate their prognostic and predictive value. Patients received pazopanib 800 mg/day as the first antiangiogenic line. The impacts of baseline neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and red cell distribution width (RDW) on PFS, OS, and Choi response were evaluated by univariate and multivariate analysis. Metastasis-free interval (MFI), mitotic count, and ECOG were also included as potential prognostic factors. Sixty-seven SFT patients, enrolled in this study, showed a median age of 63 years and a female/male distribution of 57/43. The median follow-up from treatment initiation was 16.8 months. High baseline NLR, PLR, and standardised RDW were significantly associated with worse PFS and OS. NLR, RDW, MFI, and mitotic count were independent variables for PFS, while RDW and ECOG were independent for OS. Further, NLR and mitotic count were independent factors for Choi response. High baseline NLR and RDW values were independent prognostic biomarkers for worse outcome in advanced SFT patients treated with pazopanib

Clinical value of next generation sequencing of plasma cell-free DNA in gastrointestinal stromal tumors

[Background] Gastrointestinal stromal tumor (GIST) initiation and evolution is commonly framed by KIT/PDGFRA oncogenic activation, and in later stages by the polyclonal expansion of resistant subpopulations harboring KIT secondary mutations after the onset of imatinib resistance. Thus, circulating tumor (ct)DNA determination is expected to be an informative non-invasive dynamic biomarker in GIST patients.[Methods] We performed amplicon-based next-generation sequencing (NGS) across 60 clinically relevant genes in 37 plasma samples from 18 GIST patients collected prospectively. ctDNA alterations were compared with NGS of matched tumor tissue samples (obtained either simultaneously or at the time of diagnosis) and cross-validated with droplet digital PCR (ddPCR).[Results] We were able to identify cfDNA mutations in five out of 18 patients had detectable in at least one timepoint. Overall, NGS sensitivity for detection of cell-free (cf)DNA mutations in plasma was 28.6%, showing high concordance with ddPCR confirmation. We found that GIST had relatively low ctDNA shedding, and mutations were at low allele frequencies. ctDNA was detected only in GIST patients with advanced disease after imatinib failure, predicting tumor dynamics in serial monitoring. KIT secondary mutations were the only mechanism of resistance found across 10 imatinib-resistant GIST patients progressing to sunitinib or regorafenib.[Conclusions] ctDNA evaluation with amplicon-based NGS detects KIT primary and secondary mutations in metastatic GIST patients, particularly after imatinib progression. GIST exhibits low ctDNA shedding, but ctDNA monitoring, when positive, reflects tumor dynamics.This research is supported by a Fero Fellowship Award (C.S.), Asociación Española Contra el Cáncer (J.P. Barcelona) (C.S.), and ISCIII PI16/01371 (C.S.). C.S. and A.V. acknowledge to the Cellex Foundation for providing facilities and equipment

Clinical value of next generation sequencing of plasma cell-free DNA in gastrointestinal stromal tumors

Gastrointestinal stromal tumor (GIST) initiation and evolution is commonly framed by KIT/PDGFRA oncogenic activation, and in later stages by the polyclonal expansion of resistant subpopulations harboring KIT secondary mutations after the onset of imatinib resistance. Thus, circulating tumor (ct)DNA determination is expected to be an informative non-invasive dynamic biomarker in GIST patients. We performed amplicon-based next-generation sequencing (NGS) across 60 clinically relevant genes in 37 plasma samples from 18 GIST patients collected prospectively. ctDNA alterations were compared with NGS of matched tumor tissue samples (obtained either simultaneously or at the time of diagnosis) and cross-validated with droplet digital PCR (ddPCR). We were able to identify cfDNA mutations in five out of 18 patients had detectable in at least one timepoint. Overall, NGS sensitivity for detection of cell-free (cf)DNA mutations in plasma was 28.6%, showing high concordance with ddPCR confirmation. We found that GIST had relatively low ctDNA shedding, and mutations were at low allele frequencies. ctDNA was detected only in GIST patients with advanced disease after imatinib failure, predicting tumor dynamics in serial monitoring. KIT secondary mutations were the only mechanism of resistance found across 10 imatinib-resistant GIST patients progressing to sunitinib or regorafenib. ctDNA evaluation with amplicon-based NGS detects KIT primary and secondary mutations in metastatic GIST patients, particularly after imatinib progression. GIST exhibits low ctDNA shedding, but ctDNA monitoring, when positive, reflects tumor dynamics

Estudios farmacogenéticos en el cáncer colorrectal: la vía del receptor del factor de crecimiento epidérmico

Resums pendent

Estudios farmacogenéticos en el cáncer colorrectal: la vía del receptor del factor de crecimiento epidérmico

La vía del factor de crecimiento epidérmico (EGFR) es fundamental en el desarrollo y progresión del cáncer colorrectal. Esta vía de señalización está implicada en la respuesta a fármacos dirigidos directamente frente a esta vía, y en la respuesta a otros agentes citotóxicos como las radiaciones ionizantes. Existen biomarcadores que predicen la falta de respuesta a estos fármacos dirigidos en los pacientes con cáncer colorrectal metastásico (CCRm). Sin embargo, un número relevante de pacientes no responde, lo que prueba la existencia de otros factores que influencian la respuesta. En el contexto de cáncer de recto localmente avanzado, cuyo tratamiento consiste en la administración de quimiorradioterapia de forma preoperatoria, no existe ningún marcador predictivo de respuesta a este tratamiento combinado. Esta tesis consiste en 3 trabajos que evalúan polimorfismos localizados en los genes EGFR, EGF, KRAS, los ligandos del EGFRanfiregulina y epiregulina, genes reparadores del ADN y el gen timidilato sintetasa como biomarcadores en cáncer colorrectal. Los resultados de estos trabajos muestran: una asociación entre un polimorfismo en la región 3'UTR del gen KRAS y la respuesta a fármacos anti-EGFR en pacientes con CCRm; una asociación entre polimorfismos localizados en la región génica de la anfiregulina y la respuesta y supervivencia en pacientes con CCRm tratados con anti-EGFR; una asociación entre polimorfismos en la región génica de la anfiregulina y en el gen EGFRy la probabilidad de respuesta completa patológica tras el tratamiento con quimiorradioterapia en pacientes con cáncer de recto locamente avanzado.The epidermal growth factor receptor pathway is essential in the development and progression of colorectal cancer. This signalling pathway is involved in the response to drugs targeting this pathway, as well as, in the response to other cytotoxic treatments like ionizing radiation. Biomarkers are available to predict response to drugs targeting EGFR pathway in metastatic colorectal cancer (mCRC). However, a relevant number of patients do not respond to treatment, highlighting the fact that other factors might influence the response. In locally advanced rectal cancer patients the standard treatment consists of preoperative chemoradiotherapy and, in this context no biomarkers have been found. This thesis consists of three studies in which polymorphisms located in EGFR, EGF, KRAS, EGFRligands amphiregulin and epiregulin and DNA repair genes are evaluated as biomarkers in colorectal cancer. Results from these studies show that: there is an association between a polymorphism located in the 3'UTR region of KRASand the response to anti-EGFR treatments in patients with mCRC; there is an association between polymorphisms located in the amphiregulin gene region and the response and survival in mCRC patients treated with anti-EGFR therapies; there is an association betweenpolymorphisms located in the amphiregulin gene region and theEGFRgene and the probability of pathological complete response after neoadjuvant chemoradioterapy in patients with locally advanced rectal cancer

Pulmonary function in patients with chronic stroke compared with a control group of healthy people matched by age and sex

[Abstract] Background: Effects of chronic stroke on pulmonary function are largely unknown. Aim: To compare lung volumes in people with chronic stroke with a control group of healthy people matched by age and sex, as well as to investigate the relationship between the lung volumes and functional capacity. Methods: A cross-sectional study involving people with chronic stroke. Cases were matched to a control group of healthy people. Lung function and the distance walked during the Six-Minute Walk Test (6MWD) were the main outcomes. Independent t-tests were used to compare pulmonary function between groups and the Pearson correlation coefficient was used to assess any relationship between lung volumes and the 6MWD in the stroke group. Results: Sixty-six participants (24 males in each group; 56.5 ± 15.5 years) were included. People with stroke presented significantly lower lung volumes when compared to the control group. The median of forced vital capacity (FVC) was 79% and peak expiratory flow was 64% of the reference value. The 6MWD was found to be weakly correlated with inspiratory reserve volume (r = 0.39, p = .03) and peak inspiratory flow (r = 0.35, p = .05). Conclusions: People with chronic stroke show decreased lung volumes when compared with healthy people and this likely impacts on their functional capacity

Kinetics of Thermal Degradation of Cellulose: Analysis Based on Isothermal and Linear Heating Data

In spite of the many studies performed, there is not yet a kinetic model to predict the thermal degradation of cellulose in isothermal and non-isothermal conditions for the full extent of conversion. A model proposed by the authors was tested on non-oxidising thermogravimetric data. The method consisted of initially fitting several isothermal and non-isothermal curves, then obtaining a critical temperature and an energy barrier from the set of fittings that resulted from different experimental conditions. While the critical temperature, approximately 226 °C, represented the minimum temperature for the degradation process, the degradation rate at a given temperature was related to both the critical temperature and the energy barrier. These results were compared with those observed in other materials. The quality of fittings obtained was superior to any other reported to date, and the results obtained from each single curve were in line with each other