RESUMEN
On August 11, 2022, FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki (DS-8201a, T-DXd, ENHERTU, Daiichi Sankyo) for adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating human epidermal growth factor receptor 2 (HER2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. The approval was based on a prespecified interim analysis of DESTINY-Lung02 (Study U206), a multi-center, randomized, dose-optimization trial in patients with NSCLC harboring activating HER2-mutations. At the approved dose of 5.4 mg/kg given intravenously every 3 weeks, the overall response rate (ORR) was 58% (95% confidence interval [CI]: 43, 71). The median duration of response was 8.7 months (95% CI: 7.1, not estimable). These results were consistent with response rates observed at the 6.4 mg/kg dose level. The most common (≥â 20%) adverse reactions were nausea, constipation, decreased appetite, vomiting, fatigue, and alopecia. The rate of interstitial lung disease (ILD) or pneumonitis was 6% at the 5.4 mg/kg dose level and 14% at the 6.4 mg/kg dose level. In the setting of similar efficacy and reduced toxicity, approval was granted for the 5.4 mg/kg dose level. The applicant conducted a randomized, dose-optimization study with guidance from the FDA Oncology Center of Excellence's Project Optimus. This is the first approval of a targeted therapy for HER2-mutated NSCLC.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Mutación , Receptor ErbB-2 , Trastuzumab , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptor ErbB-2/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Femenino , Trastuzumab/uso terapéutico , Trastuzumab/farmacología , Masculino , Persona de Mediana Edad , Estados Unidos , United States Food and Drug Administration , Aprobación de Drogas , Anciano , Inmunoconjugados/uso terapéutico , Inmunoconjugados/farmacología , Inmunoconjugados/efectos adversos , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Camptotecina/farmacología , Camptotecina/efectos adversos , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/farmacologíaRESUMEN
AIM: To determine post-surgical cognitive risk and associated factors according to lesion location in a sample of patients evaluated for epilepsy surgery with Wada test at the Fundacion Instituto Neurologico de Colombia. MATERIALS AND METHODS: An observational, retrospective, analytical study was completed in patients with drug-resistant temporal lobe epilepsy candidates for epilepsy surgery treated from 2001 to 2021, who completed the Wada test as part of the pre-surgical evaluation. A descriptive analysis of sociodemographic, clinical, imaging and neuropsychological variables was completed; a multivariate logistic regression was performed analyzing factors associated with resection risk in patients with left lesions. RESULTS A total of 369 patients were included, 54.74% of the cases were women, with a median age of seizure onset of 11 years. 92.66% of the cases had lesional epilepsy and 68.56% were secondary to hippocampal sclerosis. Left hemisphere was the most frequently affected (65.68%) being dominant for memory and language in most of the patients with a proportion of 42.82% and 81.3%, respectively. The median functional adequacy was 43.75 (IQR 0-75) and the functional reserve was 75 (IQR 25 -93.75). In 104 patients, the Wada test determined a resection risk. In patients with a left lesion, it was found that functional reserve (PRadjusted 0.99, CI 95% 0.9997-0.9998) and having a right hemispheric dominance for memory (PRadjusted 0.92, CI 95% 0.547-0.999) were protective factors for post-surgical resection risk. CONCLUSION: Wada test is a useful tool for surgical decision-making in patients with drug-resistant temporal lobe epilepsy. When considering cognitive risk, components such as memory dominance and functional reserve should be considered as protective factors for postsurgical cognitive function preservation in patients with left lesions.
TITLE: Evaluación de la memoria y el lenguaje mediante el test de Wada en pacientes candidatos a cirugía de epilepsia.Objetivo. Determinar el riesgo cognitivo posquirúrgico y factores asociados según la localización de la lesión en una muestra de pacientes evaluados para cirugía de epilepsia con el test de Wada en la Fundación Instituto Neurológico de Colombia. Materiales y métodos. Se realizó un estudio observacional, retrospectivo y analítico en pacientes con epilepsia farmacorresistente del lóbulo temporal candidatos a cirugía de epilepsia tratados entre 2001 y 2021, que completaron el test de Wada como parte de la evaluación prequirúrgica. Se realizó un análisis descriptivo de variables sociodemográficas, clínicas, imagenológicas y neuropsicológicas. Se realizó una regresión logística multivariada analizando factores asociados al riesgo de resección en pacientes con lesiones izquierdas. Resultados. Se incluyó a 369 pacientes, el 54,74% de los casos fueron mujeres, con una mediana de edad de inicio de las convulsiones de 11 años. El 92,66% de los casos presentó epilepsia lesional; de éstos, el 68,56% fue secundario a esclerosis hipocampal. El hemisferio izquierdo fue el más frecuentemente afectado (65,68%), y éste fue dominante para la memoria y el lenguaje en la mayoría de los pacientes, con una proporción del 42,82 y el 81,3%, respectivamente. La mediana de adecuación funcional fue de 43,75 (rango intercuartílico: 0-75) y la reserva funcional de 75 (rango intercuartílico: 25-93,75). En 104 pacientes, el test de Wada determinó un riesgo de resección. En pacientes con lesiones izquierdas se encontró que la reserva funcional (razón de prevalencia ajustada: 0,99; intervalo de confianza al 95%: 0,9997-0,9998) y tener dominancia del hemisferio derecho para la memoria (razón de prevalencia ajustada: 0,92; intervalo de confianza al 95%: 0,547-0,999) fueron factores asociados para determinar el riesgo de resección posquirúrgico en el test de Wada. Conclusión. El test de Wada es una herramienta útil para la toma de decisiones quirúrgicas en pacientes con epilepsia del lóbulo temporal farmacorresistente. Componentes como la dominancia de la memoria y la reserva funcional en el test de Wada deben considerarse como factores que se deben tener en cuenta en la predicción de la preservación de la función cognitiva posquirúrgica en pacientes con lesiones izquierdas.
Asunto(s)
Epilepsia Refractaria , Epilepsia del Lóbulo Temporal , Humanos , Femenino , Masculino , Estudios Retrospectivos , Adulto , Medición de Riesgo , Epilepsia del Lóbulo Temporal/cirugía , Epilepsia Refractaria/cirugía , Pruebas Neuropsicológicas , Complicaciones Posoperatorias/etiología , Adulto Joven , Adolescente , Niño , LenguajeRESUMEN
Introduction: Parents of children with neuromuscular diseases experience multiple difficulties in their daily lives that affect their physical and psychological health. The risk factors for these health issues have not been sufficiently investigated. Therefore, the aim of this study was to analyze the potential predictors of overload in these parents, including QoL, somatic symptomatology, life satisfaction, psychological adjustment and certain sociodemographic variables. Methods: A cross-sectional research study was conducted among parents who are caregivers for children with NMD in Spain. A convenience sample of 110 parents who were contacted by associations and hospitals was used. Variables were evaluated using the sociodemographic questionnaire, CarerQol-7D, PHQ-15, Barthel Index, Psychological Adaptation Scale, Zarit Overload Scale and Satisfaction with Life Scale. Results: One of the most relevant findings of the present study is the identification of 3 overload groups (mild to moderate, moderate to severe, and severe overload) based on life satisfaction and somatic symptom scores within the predictive model of the discriminate analysis. Wilk's lambda of the discriminant function was 0.568, χ2 (2, n = 55) = 8.815, p < 0.001. Discussion: This study presents a model that reveals the influence of unemployment, having a child with a severe level of dependency, the presence of somatic symptomatology and life satisfaction on caregiver overload. Likewise, the caregiver's self-esteem could be a protective factor against overload.
RESUMEN
Cortical electro-encephalography (EEG) served as the clinical reference for monitoring unconsciousness during general anesthesia. The existing EEG-based monitors classified general anesthesia states as underdosed, adequate, or overdosed, lacking predictive power due to the absence of transition phases among these states. In response to this limitation, we undertook an analysis of the EEG signal during isoflurane-induced general anesthesia in mice. Adopting a data-driven approach, we applied signal processing techniques to track θ- and δ-band dynamics, along with iso-electric suppressions. Combining this approach with machine learning, we successfully developed an automated algorithm. The findings of our study revealed that the dampening of the δ-band occurred several minutes before the onset of significant iso-electric suppression episodes. Furthermore, a distinct γ-frequency oscillation was observed, persisting for several minutes during the recovery phase subsequent to isoflurane-induced overdose. As a result of our research, we generated a map summarizing multiple brain states and their transitions, offering a tool for predicting and preventing overdose during general anesthesia. The transition phases identified, along with the developed algorithm, have the potential to be generalized, enabling clinicians to prevent inadequate anesthesia and, consequently, tailor anesthetic regimens to individual patients.
Asunto(s)
Isoflurano , Humanos , Ratones , Animales , Isoflurano/farmacología , Electroencefalografía , Anestesia General , Inconsciencia , EncéfaloRESUMEN
Patients with short telomere syndromes (STS) are predisposed to developing cancer, believed to stem from chromosome instability in neoplastic cells. We tested this hypothesis in a large cohort assembled over the last 20 years. We found that the only solid cancers to which patients with STS are predisposed are squamous cell carcinomas of the head and neck, anus, or skin, a spectrum reminiscent of cancers seen in patients with immunodeficiency. Whole-genome sequencing showed no increase in chromosome instability, such as translocations or chromothripsis. Moreover, STS-associated cancers acquired telomere maintenance mechanisms, including telomerase reverse transcriptase (TERT) promoter mutations. A detailed study of the immune status of patients with STS revealed a striking T cell immunodeficiency at the time of cancer diagnosis. A similar immunodeficiency that impaired tumor surveillance was documented in mice with short telomeres. We conclude that STS patients' predisposition to solid cancers is due to T cell exhaustion rather than autonomous defects in the neoplastic cells themselves.
Asunto(s)
Carcinoma de Células Escamosas , Telomerasa , Animales , Ratones , Telómero/genética , Telómero/metabolismo , Carcinoma de Células Escamosas/genética , Inestabilidad Cromosómica , Mutación , Telomerasa/genética , Telomerasa/metabolismo , Linfocitos T/metabolismoRESUMEN
The early introduction of a low phenylalanine (Phe) diet has been demonstrated to be the most successful treatment in subjects with phenylketonuria (PKU), especially for preventing severe cognitive and neurological damages. However, it still concerns that even if treated in the first months of life with supplements and following a diet, they can show slight scores below people without PKU in neuropsychological assignments. We investigated 20 adults with classical PKU aged 19-48 years (mean age 29 years) and 20 heathy controls matched by age, gender, and years of education. Patients and controls were assessed with an extended neuropsychological battery, as well as psychological aspects and quality of life, also the last Phe level result was obtained. Results showed that the most affected cognitive domains are processing speed, executive functioning, memory, and also theory of mind, but very well-preserved verbal fluency, language, and visuospatial functioning. In quality of life, some significant results were seen specially in anxiety of Phe levels, anxiety of Phe levels during pregnancy, guilt if poor adherence to supplements, and if dietary protein restriction not followed. No significant results were obtained for the psychological variables. In conclusion, it has been shown that a combination of a low Phe diet, supplement intake, and keeping Phe levels in a low range seems appropriate to have the most normal and alike cognitive performance to persons without PKU.
Asunto(s)
Fenilcetonurias , Calidad de Vida , Humanos , Adulto , Fenilalanina , Cognición , Fenilcetonurias/metabolismo , Fenilcetonurias/psicología , Función EjecutivaRESUMEN
In the era of precision oncology, use of circulating tumor DNA (ctDNA) is emerging as a minimally invasive approach for the diagnosis and management of patients with cancer and as an enrichment tool in clinical trials. In recent years, the US Food and Drug Administration has approved multiple ctDNA-based companion diagnostic assays for the safe and effective use of targeted therapies and ctDNA-based assays are also being developed for use with immuno-oncology-based therapies. For early-stage solid tumor cancers, ctDNA may be particularly important to detect molecular residual disease (MRD) to support early implementation of adjuvant or escalated therapy to prevent development of metastatic disease. Clinical trials are also increasingly using ctDNA MRD for patient selection and stratification, with an ultimate goal of improving trial efficiency through use of an enriched patient population. Standardization and harmonization of ctDNA assays and methodologies, along with further clinical validation of ctDNA as a prognostic and predictive biomarker, are necessary before ctDNA may be considered as an efficacy-response biomarker to support regulatory decision making.
Asunto(s)
ADN Tumoral Circulante , Medicina de Precisión , Estados Unidos , Humanos , Medicina de Precisión/métodos , ADN Tumoral Circulante/genética , Oncología Médica , Pronóstico , Neoplasia ResidualRESUMEN
An analysis of the scientific production of Ecuador is performed by means of the composite indicator computed for Ecuador-based authors as compared to their counterparts of other South American countries. The dataset employed was obtained from the Databricks platform of the ELSEVIER's International Center for Science Research, ICSR. Therefore, this analysis is limited to the metadata of the documents published in journals indexed in SCOPUS. Comparison of the results obtained for two decades: 2001-2010 and 2011-2020 showed that the number of Ecuador-based researchers has significantly increased in different areas of knowledge. Moreover, comparison between the total number of authors that worked in Ecuador at any given year of the 2011-2020 period and the number of authors that are still working in this country up to the date of the data extraction (i.e., June 2021) showed an average of â¼68% of permanency. Analysis of the percentage distribution in terms of range quarters of the composite indicator (i.e., Q4: 0-1.5, Q3: 1.5-3.0, Q2: 3.0-4.5, and Q1: 4.5-6.0) showed that nearly the totality of the Ecuador-based researchers has composite indicators that lay in the Q4 and Q3 ranges for all the scientific fields considered. The latter was observed to be an effect of the scientific impact of South American countries, with larger investments in science and technology in comparison to Ecuador (i.e., Argentina, Brazil, and Chile). Exclusion of this group of countries in the calculation of the composite indicator of Ecuador-based authors resulted in a noticeable increment of scientists with composite indicators within Q2. Finally, our results suggest, in agreement with previous studies, a correlation between the sustained growth of scientific productivity in the decade 2011-2020 with the scientific programs and policies created by the state, where the initiative of scientific culture is shown as a strategy for growth and development.
RESUMEN
Cellular susceptibility to SARS-CoV-2 infection in the respiratory tract has been associated with the ability of the virus to interact with potential receptors on the host membrane. We have modeled viral dynamics by simulating various cellular systems and artificial conditions, including macromolecular crowding, based on experimental and transcriptomic data to infer parameters associated with viral growth and predict cell susceptibility. We have accomplished this based on the type, number and level of expression of the angiotensin-converting enzyme 2 (ACE2), transmembrane serine 2 (TMPRSS2), basigin2 (CD147), FURIN protease, neuropilin 1 (NRP1) or other less studied candidate receptors such as heat shock protein A5 (HSPA5) and angiotensin II receptor type 2 (AGTR2). In parallel, we studied the effect of simulated artificial environments on the accessibility to said proposed receptors. In addition, viral kinetic behavior dependent on the degree of cellular susceptibility was predicted. The latter was observed to be more influenced by the type of proteins and expression level, than by the number of potential proteins associated with the SARS CoV-2 infection. We predict a greater theoretical propensity to susceptibility in cell lines such as NTERA-2, SCLC-21H, HepG2 and Vero6, and a lower theoretical propensity in lines such as CaLu3, RT4, HEK293, A549 and U-251MG. An important relationship was observed between expression levels, protein diffusivity, and thermodynamically favorable interactions between host proteins and the viral spike, suggesting potential sites of early infection other than the lungs. This research is expected to stimulate future quantitative experiments and promote systematic investigation of the effect of crowding presented here.
Asunto(s)
COVID-19 , Células HEK293 , Humanos , SARS-CoV-2 , Internalización del VirusRESUMEN
On October 2, 2020, FDA approved nivolumab with ipilimumab as first-line treatment for adult patients with unresectable malignant pleural mesothelioma (MPM). The approval was based on results from Study CA209743 (CHECKMATE-743), an open-label trial of patients with MPM randomized to receive nivolumab and ipilimumab for up to 2 years (n = 303) or six cycles of chemotherapy with cisplatin or carboplatin plus pemetrexed (n = 302). Overall survival (OS) was improved for patients who received nivolumab and ipilimumab, with a median OS of 18.1 months [95% confidence interval (CI), 16.8-21.5] compared with 14.1 months (95% CI: 12.5-16.2; HR, 0.74; 95% CI, 0.61-0.89; P = 0.002), for patients who received chemotherapy. The magnitude of benefit was larger for patients with non-epithelioid versus epithelioid histology. Additional clinical pharmacology data support an alternative dosing regimen of nivolumab than evaluated in the trial, which will reduce the number of required treatment visits. This application was reviewed under FDA's Project Orbis, in collaboration with Australia's Therapeutic Goods Administration, Switzerland's Swissmedic, Health Canada, and Brazil's National Health Surveillance Agency or ANVISA (Agência Nacional de Vigilância Sanitária). Nivolumab and ipilimumab is the first drug regimen approved by FDA for MPM since 2004.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Aprobación de Drogas , Ipilimumab/administración & dosificación , Mesotelioma Maligno/tratamiento farmacológico , Nivolumab/administración & dosificación , Neoplasias Pleurales/tratamiento farmacológico , Anciano , Femenino , Humanos , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
INTRODUCTION: Mucopolysaccharidosis type III (MPS III) or Sanfilippo syndrome is a neurodegenerative disease caused by the accumulation of mucopolysaccharides in the body. As the symptoms are wide ranging, it is a challenge to provide a diagnosis and psychological treatment for affected children. METHOD: The main objective of this study was to describe a form of music therapy treatment applied to three children diagnosed with MPS III. The psychological variables were evaluated by an ad hoc observation recording template, and the physiological variables were measured with a digital meter before and after each session. The perception of the parents was also considered through a semi-structured interview. RESULTS: An improvement in the psychological variables was shown in all cases. Changes in the physiological variables were also noted, although they varied according to each child. The parents report some benefit of music therapy and they share difficulty in assessing the extent of benefits of the music therapy. DISCUSSION: Findings indicate that music therapy can be a useful form of treatment with multiple benefits for children with conditions such as MPS III or similar conditions. However, further research is needed in this area and in the development of specific ways of evaluating music therapy.
Asunto(s)
Mucopolisacaridosis III , Musicoterapia , Enfermedades Neurodegenerativas , Niño , Glicosaminoglicanos , Humanos , Mucopolisacaridosis III/diagnóstico , Mucopolisacaridosis III/terapia , Padres/psicologíaRESUMEN
The COVID-19 pandemic has accelerated the study of the potential of multi-target drugs (MTDs). The mixture of homologues called ivermectin (avermectin-B1a + avermectin-B1b) has been shown to be a MTD with potential antiviral activity against SARS-CoV-2 in vitro. However, there are few reports on the effect of each homologue on the flexibility and stiffness of proteins associated with COVID-19, described as ivermectin targets. We observed that each homologue was stably bound to the proteins studied and was able to induce detectable changes with Elastic Network Models (ENM). The perturbations induced by each homologue were characteristic of each compound and, in turn, were represented by a disruption of native intramolecular networks (interactions between residues). The homologues were able to slightly modify the conformation and stability of the connection points between the Cα atoms of the residues that make up the structural network of proteins (nodes), compared to free proteins. Each homologue was able to modified differently the distribution of quasi-rigid regions of the proteins, which could theoretically alter their biological activities. These results could provide a biophysical-computational view of the potential MTD mechanism that has been reported for ivermectin.
RESUMEN
The SARS-CoV-2 pandemic has accelerated the study of existing drugs. The mixture of homologs called ivermectin (avermectin-B1a [HB1a] + avermectin-B1b [HB1b]) has shown antiviral activity against SARS-CoV-2 in vitro. However, there are few reports on the behavior of each homolog. We investigated the interaction of each homolog with promising targets of interest associated with SARS-CoV-2 infection from a biophysical and computational-chemistry perspective using docking and molecular dynamics. We observed a differential behavior for each homolog, with an affinity of HB1b for viral structures, and of HB1a for host structures considered. The induced disturbances were differential and influenced by the hydrophobicity of each homolog and of the binding pockets. We present the first comparative analysis of the potential theoretical inhibitory effect of both avermectins on biomolecules associated with COVID-19, and suggest that ivermectin through its homologs, has a multiobjective behavior.
Asunto(s)
Antivirales/química , Proteasas 3C de Coronavirus/antagonistas & inhibidores , ADN Helicasas/antagonistas & inhibidores , Ivermectina/análogos & derivados , alfa Carioferinas/antagonistas & inhibidores , beta Carioferinas/antagonistas & inhibidores , Animales , Antivirales/farmacología , Sitios de Unión , COVID-19/virología , Proteasas 3C de Coronavirus/química , Proteasas 3C de Coronavirus/metabolismo , ADN Helicasas/química , ADN Helicasas/metabolismo , Humanos , Ivermectina/química , Ivermectina/farmacología , Cinética , Ratones , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Unión Proteica , Conformación Proteica , Dominios y Motivos de Interacción de Proteínas , SARS-CoV-2/química , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/enzimología , Termodinámica , alfa Carioferinas/química , alfa Carioferinas/metabolismo , beta Carioferinas/química , beta Carioferinas/metabolismo , Tratamiento Farmacológico de COVID-19RESUMEN
Our purpose is to report the intermediate-term results of the Ex-PRESS® implant as the first surgical option in patients with Iridocorneal Endothelial (ICE) Syndrome. We describe two patients diagnosed from ICE syndrome with medically uncontrolled glaucoma and finally treated with an Ex-PRESS® implant, associating a cataract surgery in one of them. Three years after surgery, intraocular pressure remains stable without any additional medical antiglaucomatous treatment, with a well-located implant surrounded by a diffuse filtering bleb and no sight-threatening adverse events have been documented. In addition, no progression of the disease has been registered. This report encourage the Ex-PRESS® implant to be considered the first surgical option in this patients as it allows a permeable ostium in spite of the progressive synechial angle closure typical of the ICE syndrome.
Asunto(s)
Implantes de Drenaje de Glaucoma , Síndrome Endotelial Iridocorneal , Estudios de Seguimiento , Humanos , Síndrome Endotelial Iridocorneal/cirugía , Tonometría Ocular , Resultado del TratamientoRESUMEN
On December 18, 2020, the FDA approved osimertinib as adjuvant therapy in patients with non-small cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or exon 21 (L858R) mutations, as detected by an FDA-approved test. The approval was based on the ADAURA study, in which 682 patients with NSCLC were randomized to receive osimertinib (n = 339) or placebo (n = 343). Disease-free survival (DFS) in the overall population (stage IB-IIIA) was improved for patients who received osimertinib, with an HR of 0.20; 95% confidence interval (CI), 0.15-0.27; P < 0.0001. Median DFS was not reached for the osimertinib arm compared with 27.5 months (95% CI, 22.0-35.0) for patients receiving placebo. Overall survival data were not mature at the time of the approval. This application was reviewed under FDA's Project Orbis, in collaboration with Australia Therapeutic Goods Administration, Brazil ANVISA, Health Canada, Singapore Health Sciences Authority, Switzerland Swissmedic, and the United Kingdom Medicines and Healthcare products Regulatory Agency. This is the first targeted therapy adjuvant approval for NSCLC and has practice-changing implications.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Acrilamidas , Compuestos de Anilina/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
Water pollution is an environmental problem in constant raising because of population growing, industrial development, agricultural frontier expansion, and principally because of the lack of wastewater treatment technology to remove organic recalcitrant and toxic pollutants from industrial and domestic wastewater. Recalcitrant compounds are a serious environmental and health problem mainly due to their toxicity and potential hazardous effects on living organisms, including human beings. Conventional wastewater treatments have not been able to remove efficiently pollutants from water; however, electrochemical advanced oxidation processes (EAOPs) are able to solve this environmental concern. One of the most recent EAOPs technology is photoelectrocatalysis (PEC), it consists in applying an external bias potential to a semiconductor film placed over a conductive substrate to avoid the recombination of photogenerated electron-hole (e-/h+) pairs, increasing h+ availability and hydroxyl radicals' formation, responsible for promoting the degradation/mineralization of organic pollutants in aqueous medium. This review summarizes the recent advances in PEC as a promising technology for wastewater treatment. It addresses the fundamentals and kinetic aspects of PEC. An analysis of photoanode materials and of the configuration of photoelectrochemical reactors is also presented, including an analysis of the influence of the main operational parameters on the treatment of contaminated water. Finally, the most recent applications of PEC are reviewed, and the challenges and perspectives of PEC in wastewater treatment are discussed.
Asunto(s)
Contaminantes Ambientales , Contaminantes Químicos del Agua , Purificación del Agua , Humanos , Oxidación-Reducción , Aguas Residuales/análisis , Agua , Contaminantes Químicos del Agua/análisisRESUMEN
On May 26, 2020, the FDA approved nivolumab with ipilimumab and two cycles of platinum-doublet chemotherapy as first-line treatment for patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or anaplastic lymphoma kinase (ALK) genomic tumor aberrations. The approval was based on results from Study CA2099LA (CheckMate 9LA), an open-label trial in which 719 patients with NSCLC were randomized to receive nivolumab with ipilimumab and two cycles of chemotherapy (n = 361) or four cycles of platinum-doublet chemotherapy (n = 358). Overall survival (OS) was improved for patients who received nivolumab with ipilimumab and chemotherapy, with a median OS of 14.1 months [95% confidence interval (CI), 13.2-16.2] compared with 10.7 months (95% CI, 9.5-12.5) for patients who received chemotherapy (HR, 0.69; 96.71% CI, 0.55-0.87; P = 0.0006). Progression-free survival and overall response rate per blinded independent central review were also statistically significant. This was the first NSCLC application reviewed under FDA's Project Orbis, in collaboration with Singapore's Health Sciences Authority, Australia's Therapeutic Goods Administration, and Health Canada. The benefit-risk analysis supports FDA's approval of nivolumab with ipilimumab and chemotherapy.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Humanos , Ipilimumab , Neoplasias Pulmonares/genética , Recurrencia Local de Neoplasia/tratamiento farmacológico , NivolumabRESUMEN
INTRODUCTION: Numerous invasive and non-invasive neuromodulation devices have been developed and applied to patients with headache and neuralgia in recent years. However, no updated review addresses their safety and efficacy, and no healthcare institution has issued specific recommendations on their use for these 2 conditions. METHODS: Neurologists from the Spanish Society of Neurology's (SEN) Headache Study Group and neurosurgeons specialising in functional neurosurgery, selected by the Spanish Society of Neurosurgery (SENEC), performed a comprehensive review of articles on the MEDLINE database addressing the use of the technique in patients with headache and neuralgia. RESULTS: We present an updated review and establish the first set of consensus recommendations of the SEN and SENC on the use of neuromodulation to treat headache and neuralgia, analysing the current levels of evidence on its effectiveness for each specific condition. CONCLUSIONS: Current evidence supports the indication of neuromodulation techniques for patients with refractory headache and neuralgia (especially migraine, cluster headache, and trigeminal neuralgia) selected by neurologists and headache specialists, after pharmacological treatment options are exhausted. Furthermore, we recommend that invasive neuromodulation be debated by multidisciplinary committees, and that the procedure be performed by teams of neurosurgeons specialising in functional neurosurgery, with acceptable rates of morbidity and mortality.
Asunto(s)
Cefalea , Trastornos Migrañosos , Cefalea/terapia , Humanos , Trastornos Migrañosos/terapia , Neuralgia/terapia , Neurología , Neurocirugia/normas , Guías de Práctica Clínica como AsuntoRESUMEN
CONTEXT: In recent years, the ketogenic diet has gained special relevance as a possible therapeutic alternative to some neurological and chronic diseases. OBJECTIVE: The aim of this systematic review was to answer the following question: Does a ketogenic diet improve cognitive skills in patients with Alzheimer's disease, Parkinson's disease, refractory epilepsy, and type 1 glucose deficiency syndrome? To define the research question, the PICOS criteria were used, following the guidelines of the PRISMA method. DATA SOURCES: Medline/PubMed, Elsevier Science Direct, Dialnet, EBSCOhost, Mediagraphic, Sage Journals, ProQuest, and Wiley Online Library databases were used. DATA EXTRACTION: After applying inclusion and exclusion criteria in accordance with the PRISMA method, a total of 63 entries published between 2004 and 2019 were used. DATA ANALYSIS: The records extracted were analyzed from a qualitative approach, so no statistical analysis was carried out. CONCLUSION: Although scientific literature on the subject is scarce and there has tended to be a lack of scientific rigor, the studies reviewed confirmed the effectiveness of this diet in improving the cognitive symptomatology of the aforementioned diseases.