Evaluation of Preprocessing Methods on Independent Medical Hyperspectral Databases to Improve Analysis.

Currently, one of the most common causes of death worldwide is cancer. The development of innovative methods to support the early and accurate detection of cancers is required to increase the recovery rate of patients. Several studies have shown that medical Hyperspectral Imaging (HSI) combined with artificial intelligence algorithms is a powerful tool for cancer detection. Various preprocessing methods are commonly applied to hyperspectral data to improve the performance of the algorithms. However, there is currently no standard for these methods, and no studies have compared them so far in the medical field. In this work, we evaluated different combinations of preprocessing steps, including spatial and spectral smoothing, Min-Max scaling, Standard Normal Variate normalization, and a median spatial smoothing technique, with the goal of improving tumor detection in three different HSI databases concerning colorectal, esophagogastric, and brain cancers. Two machine learning and deep learning models were used to perform the pixel-wise classification. The results showed that the choice of preprocessing method affects the performance of tumor identification. The method that showed slightly better results with respect to identifing colorectal tumors was Median Filter preprocessing (0.94 of area under the curve). On the other hand, esophagogastric and brain tumors were more accurately identified using Min-Max scaling preprocessing (0.93 and 0.92 of area under the curve, respectively). However, it is observed that the Median Filter method smooths sharp spectral features, resulting in high variability in the classification performance. Therefore, based on these results, obtained with different databases acquired by different HSI instrumentation, the most relevant preprocessing technique identified in this work is Min-Max scaling.

Neural Networks-Based On-Site Dermatologic Diagnosis through Hyperspectral Epidermal Images.

Cancer originates from the uncontrolled growth of healthy cells into a mass. Chromophores, such as hemoglobin and melanin, characterize skin spectral properties, allowing the classification of lesions into different etiologies. Hyperspectral imaging systems gather skin-reflected and transmitted light into several wavelength ranges of the electromagnetic spectrum, enabling potential skin-lesion differentiation through machine learning algorithms. Challenged by data availability and tiny inter and intra-tumoral variability, here we introduce a pipeline based on deep neural networks to diagnose hyperspectral skin cancer images, targeting a handheld device equipped with a low-power graphical processing unit for routine clinical testing. Enhanced by data augmentation, transfer learning, and hyperparameter tuning, the proposed architectures aim to meet and improve the well-known dermatologist-level detection performances concerning both benign-malignant and multiclass classification tasks, being able to diagnose hyperspectral data considering real-time constraints. Experiments show 87% sensitivity and 88% specificity for benign-malignant classification and specificity above 80% for the multiclass scenario. AUC measurements suggest classification performance improvement above 90% with adequate thresholding. Concerning binary segmentation, we measured skin DICE and IOU higher than 90%. We estimated 1.21 s, at most, consuming 5 Watts to segment the epidermal lesions with the U-Net++ architecture, meeting the imposed time limit. Hence, we can diagnose hyperspectral epidermal data assuming real-time constraints.

Mindfulness based intervention through mobile app for colorectal cancer people awaiting surgery: A randomized clinical trial.

INTRODUCTION: Colorectal cancer is the third most common cancer worldwide both in men and women. Around one-third of patients with cancer will suffer from anxiety or depression symptoms. The aim of this study was to evaluate the effectiveness of a Mindfulness-based stress reduction intervention through a mobile application ("En Calma en el Quirófano"). METHOD: This study is a multicenter, single-blind (evaluator), controlled, randomised trial that compares the effectiveness of a mindfulness training through a mobile application (intervention group) and treatment as usual (control group) in three different moments (T0 or baseline, T1 or hospital discharge and T2 or one month after surgery). Anxiety and depression symptoms (HADS), quality of life (WHOQOL), pain, (VAS) and satisfaction (CSQ) were assessed. RESULTS: In all, there were 270 referred patients. Among them, 39 and 43 were assigned to the intervention and control groups respectively. 82 patients were analyzed: 39 patients used the app, and 43 patients continued with the treatment as usual. There were no significant changes between groups and time. We observed a slight trend in which intervention group had less depression and anxiety symptoms since T0 and T2 (B = -0.2; 95% CI between 8.8 and 9.2). CONCLUSIONS: The sample of this study had a high mean age (65 years old), and low levels of anxiety and depression and medium levels of pre-surgery quality of life in baseline. These factors could have influenced limiting the effectiveness of the app. Prospective research lines should focus on evaluating the effectiveness of mobile applications for younger patients with surgical pathologies.

Deep Convolutional Generative Adversarial Networks to Enhance Artificial Intelligence in Healthcare: A Skin Cancer Application.

In recent years, researchers designed several artificial intelligence solutions for healthcare applications, which usually evolved into functional solutions for clinical practice. Furthermore, deep learning (DL) methods are well-suited to process the broad amounts of data acquired by wearable devices, smartphones, and other sensors employed in different medical domains. Conceived to serve the role of diagnostic tool and surgical guidance, hyperspectral images emerged as a non-contact, non-ionizing, and label-free technology. However, the lack of large datasets to efficiently train the models limits DL applications in the medical field. Hence, its usage with hyperspectral images is still at an early stage. We propose a deep convolutional generative adversarial network to generate synthetic hyperspectral images of epidermal lesions, targeting skin cancer diagnosis, and overcome small-sized datasets challenges to train DL architectures. Experimental results show the effectiveness of the proposed framework, capable of generating synthetic data to train DL classifiers.

A case of a large leiomyomatous uterus with multiple arteriovenous malformations and subsequent high cardiac output state with severe four chamber cardiac enlargement.

Uterine arteriovenous malformations (AVMs) are rare and potentially life-threatening. They can be congenital or acquired. Uterine artery embolization or hysterectomy are considered mainstays of management. AVMs can be associated with leiomyomas, and patients may require both procedures. We present a case of a 42-year-old woman with a massively enlarged leiomyomatous uterus supplied and drained by multiple large AVMs, leading to high cardiac output state with severe four chamber cardiac dilation. Management required a multidisciplinary team of interventional radiology, gynecologic oncology surgery, vascular surgery, cardiac anesthesiology, cardiology, and urology and a 2-day interventional approach of preoperative arterial embolization followed by hysterectomy.

L-Arginine Ameliorates Defective Autophagy in GM2 Gangliosidoses by mTOR Modulation.

AIMS: Tay-Sachs and Sandhoff diseases (GM2 gangliosidosis) are autosomal recessive disorders of lysosomal function that cause progressive neurodegeneration in infants and young children. Impaired hydrolysis catalysed by ß-hexosaminidase A (HexA) leads to the accumulation of GM2 ganglioside in neuronal lysosomes. Despite the storage phenotype, the role of autophagy and its regulation by mTOR has yet to be explored in the neuropathogenesis. Accordingly, we investigated the effects on autophagy and lysosomal integrity using skin fibroblasts obtained from patients with Tay-Sachs and Sandhoff diseases. RESULTS: Pathological autophagosomes with impaired autophagic flux, an abnormality confirmed by electron microscopy and biochemical studies revealing the accelerated release of mature cathepsins and HexA into the cytosol, indicating increased lysosomal permeability. GM2 fibroblasts showed diminished mTOR signalling with reduced basal mTOR activity. Accordingly, provision of a positive nutrient signal by L-arginine supplementation partially restored mTOR activity and ameliorated the cytopathological abnormalities. INNOVATION: Our data provide a novel molecular mechanism underlying GM2 gangliosidosis. Impaired autophagy caused by insufficient lysosomal function might represent a new therapeutic target for these diseases. CONCLUSIONS: We contend that the expression of autophagy/lysosome/mTOR-associated molecules may prove useful peripheral biomarkers for facile monitoring of treatment of GM2 gangliosidosis and neurodegenerative disorders that affect the lysosomal function and disrupt autophagy.

La educación alimentaria y nutricional: un estudio descriptivo en la formación del docente de Biología / Food and nutritional education: descriptive study in the training of Biology teachers

RESUMEN Introducción: el docente de Biología debe contribuir a la educación para la salud, y dentro de ella a la educación alimentaria y nutricional de los estudiantes, mediante el proceso de enseñanza-aprendizaje de los contenidos relacionados con la Biología. Objetivo: describir los conocimientos y comportamientos sobre educación alimentaria y nutricional que poseen los estudiantes de la carrera de Licenciatura en Educación, especialidad Biología, en la Universidad de Matanzas. Materiales y métodos: se realizó un estudio descriptivo de los conocimientos y comportamientos sobre educación alimentaria y nutricional en 21 estudiantes de la carrera de Licenciatura en Educación, especialidad Biología, de la Universidad de Matanzas, en enero de 2020. Los métodos teóricos empleados fueron el histórico-lógico, el analítico-sintético y el inductivo-deductivo. Como método empírico se utilizó la encuesta. Resultados: los estudiantes presentan insuficientes conocimientos sobre los nutrientes que aportan diversos alimentos, y desconocimiento sobre las biomoléculas y su importancia para el correcto funcionamiento del organismo. Muestran interés por el consumo de la comida denominada chatarra, y obvian la necesidad del consumo de vegetales, frutas y viandas hervidas. Conclusiones: los estudiantes encuestados presentaron limitados conocimientos sobre alimentación y nutrición como procesos inherentes a la vida humana, que determinan la educación alimentaria y nutricional como un factor básico para evitar enfermedades que repercuten en su salud, e impiden que puedan realizar su labor educativa como docentes de Biología, líderes de la promoción de salud en la escuela y la comunidad (AU).

ABSTRACT Introduction: the teacher who teaches Biology must make good use of the different curricular contents to contribute to health education and within it to food and nutritional education of students. Objective: to describe the knowledge and behaviors on food and nutrition education that students of the degree course of Education in Biology of the University of Matanzas have. Materials and methods: a descriptive study of the knowledge and behavior on food and nutritional education in 21 students of the degree course of Education in Biology of the University of Matanzas, in January 2020. The theoretical methods used were the historic-logical, the analytical-synthetic, and the inductive-deductive one. The survey was used as empiric method. Results: the students showed not enough knowledge on the nutrients provided by different foods, not knowing about biomolecules and their importance for the proper functioning of the body. They evidenced their preference for the consumption of the so called junk food, obviating the need of green vegetables, fruits and boiled vegetables. Conclusions: the surveyed students presented limited knowledge on food and nutrition as processes inherent to human life, which determine food and nutritional education as a basic factor to avoid diseases that affect their health. It is a constraint for carrying out an adequate educative work as Biology teachers and future leaders of health promotion at school and in the community (AU).

Analysis of Risk Factors in Dementia Through Machine Learning.

BACKGROUND: Sociodemographic data indicate the progressive increase in life expectancy and the prevalence of Alzheimer's disease (AD). AD is raised as one of the greatest public health problems. Its etiology is twofold: on the one hand, non-modifiable factors and on the other, modifiable. OBJECTIVE: This study aims to develop a processing framework based on machine learning (ML) and optimization algorithms to study sociodemographic, clinical, and analytical variables, selecting the best combination among them for an accurate discrimination between controls and subjects with major neurocognitive disorder (MNCD). METHODS: This research is based on an observational-analytical design. Two research groups were established: MNCD group (n = 46) and control group (n = 38). ML and optimization algorithms were employed to automatically diagnose MNCD. RESULTS: Twelve out of 37 variables were identified in the validation set as the most relevant for MNCD diagnosis. Sensitivity of 100%and specificity of 71%were achieved using a Random Forest classifier. CONCLUSION: ML is a potential tool for automatic prediction of MNCD which can be applied to relatively small preclinical and clinical data sets. These results can be interpreted to support the influence of the environment on the development of AD.

Vacunación sublingual con bacterias inactivadas en pacientes nefrológicos con infección urinaria recurrente: experiencia en un centro de España / Sublingual vaccination with inactivated bacteria in recurrent urinary tract infection of nephrologic patients: experience in a center in Spain

Resumen Introducción: las infecciones del tracto urinario (ITU) son frecuentes en pacientes con enfermedad renal crónica (ERC). Una opción de tratamiento cuando estas infecciones son recurrentes es la vacunación bacteriana sublingual. Objetivo: determinar la respuesta a la vacunación bacteriana sublingual en pacientes nefrológicos con ITU recurrente. Materiales y métodos: estudio cuasi experimental en el que se evaluó la evolución en 15 meses de los pacientes con ITU recurrente que asistieron a consulta externa de nefrología. Tras recibir tratamiento antibiótico según antibiograma para cada ITU, los participantes tomaron un ciclo de la vacuna sublingual bacteriana Uromune® durante tres meses. Se recogieron datos sociodemográficos y sobre factores de riesgo asociados, análisis de sangre y orina, episodios de ITU en los seis meses previos y posteriores, microorganismos causantes, tratamiento antibiótico concomitante, respuesta al tratamiento y resolución de la ITU. Resultados: se incluyeron 26 pacientes (80,8 % mujeres) con una media de edad de 61,9±18,4 años, de los cuales el 46,2 % tenía diabetes y el 47,7 %, afectación de la función renal. La media de ITU fue 3,62±1,77 (rango: 1 -7) antes de la vacuna y de 1,69±1,77 (rango: 0-5) después. Se recogieron 184 urocultivos: 74,9 % positivos, 16,9 % negativos y 8,2 % contaminados. Las bacterias más frecuentes fueron Escherichia coli (55,4 %), Enterococcus faecalis (6 %) y Enterobacter cloacae (2,7 %). El 50 % de los participan- tes presentó síndrome miccional, que se asoció inversamente con la edad (p<0,05). El 26,9 % no volvió a tener ITU y el 73,1 % tuvo menos episodios. Los pacientes con ERC avanzada (estadios IV-V) respondieron peor a la vacuna (92,9 % vs 50 %, p=0,025). Conclusiones: la vacunación bacteriana sublingual es una buena opción de tratamiento para la ITU recurrente de pacientes con ERC, siendo más eficaz en los que presentan mejor función renal.

Abstract Introduction: Urinary tract infections (UTIs) are common in patients with chronic kidney disease. A treatment option in recurrent UTI is sublingual bacterial vaccination. The objective of this study was to determine the response to vaccination in nephrologic patients with recurrent UTI. Method: Quasi-experimental study before-after (15 months) in patients with recurrent UTI from the outpatient nephrology consultation. After receiving antibiotic treatment for each UTI, patients took one cycle of the sublingual bacterial vaccine Uromune? for three months. Sociodemographic data, associated risk factors, analysis, UTI in the previous and subsequent six months, microorganisms, concomitant antibiotic treatment, response to treatment and resolution of UTI were collected. Results: Twenty-six patients (80.8% female) of 61.9 ±18.4 years, 46.2% with diabetes and 47.7% with impaired renal function were included. The episodes of UTI were 3.62 ±1.77 (1-7) before and 1.69 ± 1.77 (0-5) after vaccination. In total, 184 urine cultures were collected: 74.9% positive, 16.9% negative and 8.2% contaminated. The most frequent bacteria were Escherichia coli (55.4%), Enterococcus faecalis (6%) and Enterobacter cloacae (2.7%). Fifty percent had voiding syndrome, which was inversely associated with age (p < 0.05); 26.9% did not have a UTI again and 73.1% had fewer episodes. Patients with advanced chronic disease (stages 4-5) reponded worse to the vaccine (92.9% vs 50%, p =0.025). Conclusions: Sublingual bacterial vaccination is a good treatment option in recurrent UTI of nephrologic patients, being more effective in those with better renal function.

A Network of Macrophages Supports Mitochondrial Homeostasis in the Heart.

Cardiomyocytes are subjected to the intense mechanical stress and metabolic demands of the beating heart. It is unclear whether these cells, which are long-lived and rarely renew, manage to preserve homeostasis on their own. While analyzing macrophages lodged within the healthy myocardium, we discovered that they actively took up material, including mitochondria, derived from cardiomyocytes. Cardiomyocytes ejected dysfunctional mitochondria and other cargo in dedicated membranous particles reminiscent of neural exophers, through a process driven by the cardiomyocyte's autophagy machinery that was enhanced during cardiac stress. Depletion of cardiac macrophages or deficiency in the phagocytic receptor Mertk resulted in defective elimination of mitochondria from the myocardial tissue, activation of the inflammasome, impaired autophagy, accumulation of anomalous mitochondria in cardiomyocytes, metabolic alterations, and ventricular dysfunction. Thus, we identify an immune-parenchymal pair in the murine heart that enables transfer of unfit material to preserve metabolic stability and organ function. VIDEO ABSTRACT.

Nutraceutical Compounds Targeting Inflammasomes in Human Diseases.

The macromolecular complex known as "inflammasome" is defined as an intracellular multi-protein complex composed of a sensor receptor (PRR), an adaptor protein and an effector enzyme (caspase-1), which oligomerize when they sense danger, such as how the NLR family, AIM-2 and RIG-1 receptors protect the body against danger via cytokine secretion. Within the NLR members, NLRP3 is the most widely known and studied inflammasome and has been linked to many diseases. Nowadays, people's interest in their lifestyles and nutritional habits is increasing, mainly due to the large number of diseases that seem to be related to both. The term "nutraceutical" has recently emerged as a hybrid term between "nutrition" and "pharmacological" and it refers to a wide range of bioactive compounds contained in food with relevant effects on human health. The relationship between these compounds and diseases based on inflammatory processes has been widely exposed and the compounds stand out as an alternative to the pathological consequences that inflammatory processes may have, beyond their defense and repair action. Against this backdrop, here we review the results of studies using several nutraceutical compounds in common diseases associated with the inflammation and activation of the NLRP3 inflammasomes complex. In general, it was found that there is a wide range of nutraceuticals with effects through different molecular pathways that affect the activation of the inflammasome complex, with positive effects mainly in cardiovascular, neurological diseases, cancer and type 2 diabetes.

Non-Invasive Skin Cancer Diagnosis Using Hyperspectral Imaging for In-Situ Clinical Support.

Skin cancer is one of the most common forms of cancer worldwide and its early detection its key to achieve an effective treatment of the lesion. Commonly, skin cancer diagnosis is based on dermatologist expertise and pathological assessment of biopsies. Although there are diagnosis aid systems based on morphological processing algorithms using conventional imaging, currently, these systems have reached their limit and are not able to outperform dermatologists. In this sense, hyperspectral (HS) imaging (HSI) arises as a new non-invasive technology able to facilitate the detection and classification of pigmented skin lesions (PSLs), employing the spectral properties of the captured sample within and beyond the human eye capabilities. This paper presents a research carried out to develop a dermatological acquisition system based on HSI, employing 125 spectral bands captured between 450 and 950 nm. A database composed of 76 HS PSL images from 61 patients was obtained and labeled and classified into benign and malignant classes. A processing framework is proposed for the automatic identification and classification of the PSL based on a combination of unsupervised and supervised algorithms. Sensitivity and specificity results of 87.5% and 100%, respectively, were obtained in the discrimination of malignant and benign PSLs. This preliminary study demonstrates, as a proof-of-concept, the potential of HSI technology to assist dermatologists in the discrimination of benign and malignant PSLs during clinical routine practice using a real-time and non-invasive hand-held device.

Integrated molecular signaling involving mitochondrial dysfunction and alteration of cell metabolism induced by tyrosine kinase inhibitors in cancer.

Cancer cells have unlimited replicative potential, insensitivity to growth-inhibitory signals, evasion of apoptosis, cellular stress, and sustained angiogenesis, invasiveness and metastatic potential. Cancer cells adequately adapt cell metabolism and integrate several intracellular and redox signaling to promote cell survival in an inflammatory and hypoxic microenvironment in order to maintain/expand tumor phenotype. The administration of tyrosine kinase inhibitor (TKI) constitutes the recommended therapeutic strategy in different malignancies at advanced stages. There are important interrelationships between cell stress, redox status, mitochondrial function, metabolism and cellular signaling pathways leading to cell survival/death. The induction of apoptosis and cell cycle arrest widely related to the antitumoral properties of TKIs result from tightly controlled events involving different cellular compartments and signaling pathways. The aim of the present review is to update the most relevant studies dealing with the impact of TKI treatment on cell function. The induction of endoplasmic reticulum (ER) stress and Ca2+ disturbances, leading to alteration of mitochondrial function, redox status and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) signaling pathways that involve cell metabolism reprogramming in cancer cells will be covered. Emphasis will be given to studies that identify key components of the integrated molecular pattern including receptor tyrosine kinase (RTK) downstream signaling, cell death and mitochondria-related events that appear to be involved in the resistance of cancer cells to TKI treatments.

Infección del tracto urinario en la enfermedad renal crónica / Urinary tract infection in chronic kidney disease patients

Resumen Las infecciones en personas con enfermedad renal crónica son una causa importante de morbimortalidad. Los pacientes renales presentan factores de riesgo específicos para la adquisición de infecciones, que además suelen ser más graves, de progresión más rápida y de resolución más lenta que en sujetos sanos. La infección del tracto urinario en esta población es a menudo complicada debido a la presencia de diabetes, microorganismos multirresistentes, anomalías anatómicas o funcionales del tracto urinario, alteraciones metabólicas y el uso frecuente de sonda vesical. Las infecciones urinarias ocasionan una de las tasas más altas de hospitalización en diálisis y son muy prevalentes en el trasplante renal. Este trabajo tiene como objetivo revisar la literatura publicada sobre la etiología, el diagnóstico microbiológico y el tratamiento de las infecciones del tracto urinario en pacientes con enfermedad renal crónica.

Abstract Infections in chronic kidney disease patients are a major cause of morbidity and mortality. Renal patients have specific risk factors for acquiring infections, which also tend to be more severe and have a more rapid progression and slower resolution than in the healthy individuals. Urinary tract infection in renal patients is often complicated due to the presence of diabetes, multiresistant microorganisms, anatomic or functional abnormalities of the urinary tract, metabolic disturbances and the frequent use of urinary catheters. It causes one of the highest rates of hospitalization among dialysis patients and is highly prevalent in kidney transplantation. The aim of this work is to review the etiology, microbiological diagnosis and treatment of urinary tract infections in chronic kidney disease patients.

Efficacy and Safety of Pembrolizumab Plus Docetaxel vs Docetaxel Alone in Patients With Previously Treated Advanced Non-Small Cell Lung Cancer: The PROLUNG Phase 2 Randomized Clinical Trial.

Importance: Because of socioeconomic factors, many patients with advanced non-small cell lung cancer (NSCLC) do not receive immunotherapy in the first-line setting. It is unknown if the combination of immunotherapy with chemotherapy can provide clinical benefits in immunotherapy-naive patients with disease progression after treatment with platinum-based chemotherapy. Objective: To evaluate the safety and efficacy of the combination of pembrolizumab plus docetaxel in patients with previously treated advanced NSCLC following platinum-based chemotherapy regardless of EGFR variants or programmed cell death ligand 1 status. Design, Setting, and Participants: The Pembrolizumab Plus Docetaxel for Advanced Non-Small Cell Lung Cancer (PROLUNG) trial randomized 78 patients with histologically confirmed advanced NSCLC in a 1:1 ratio to receive either pembrolizumab plus docetaxel or docetaxel alone from December 2016 through May 2019. Interventions: The experimental arm received docetaxel on day 1 (75 mg/m2) plus pembrolizumab on day 8 (200 mg) every 3 weeks for up to 6 cycles followed by pembrolizumab maintenance until progression or unacceptable toxic effects. The control arm received docetaxel monotherapy. Main Outcomes and Measures: The primary end point was overall response rate (ORR). Secondary end points included progression-free survival (PFS), overall survival, and safety. Results: Among 78 recruited patients, 32 (41%) were men, 34 (44%) were never smokers, and 25 (32%) had an EGFR/ALK alteration. Forty patients were allocated to receive pembrolizumab plus docetaxel, and 38 were allocated to receive docetaxel. A statistically significant difference in ORR, assessed by an independent reviewer, was found in patients receiving pembrolizumab plus docetaxel vs patients receiving docetaxel (42.5% vs 15.8%; odds ratio, 3.94; 95% CI, 1.34-11.54; P = .01). Patients without EGFR variations had a considerable difference in ORR of 35.7% vs 12.0% (P = .06), whereas patients with EGFR variations had an ORR of 58.3% vs 23.1% (P = .14). Overall, PFS was longer in patients who received pembrolizumab plus docetaxel (9.5 months; 95% CI, 4.2-not reached) than in patients who received docetaxel (3.9 months; 95% CI, 3.2-5.7) (hazard ratio, 0.24; 95% CI, 0.13-0.46; P < .001). For patients without variations, PFS was 9.5 months (95% CI, 3.9-not reached) vs 4.1 months (95% CI, 3.5-5.3) (P < .001), whereas in patients with EGFR variations, PFS was 6.8 months (95% CI, 6.2-not reached) vs 3.5 months (95% CI, 2.3-6.2) (P = .04). In terms of safety, 23% (9 of 40) vs 5% (2 of 38) of patients experienced grade 1 to 2 pneumonitis in the pembrolizumab plus docetaxel and docetaxel arms, respectively (P = .03), while 28% (11 of 40) vs 3% (1 of 38) experienced any-grade hypothyroidism (P = .002). No new safety signals were identified. Conclusions and Relevance: In this phase 2 study, the combination of pembrolizumab plus docetaxel was well tolerated and substantially improved ORR and PFS in patients with advanced NSCLC who had previous progression after platinum-based chemotherapy, including NSCLC with EGFR variations. Trial Registration: ClinicalTrials.gov Identifier: NCT02574598.

NLRP3 Inflammasome Inhibition by MCC950 in Aged Mice Improves Health via Enhanced Autophagy and PPARα Activity.

The NLRP3 inflammasome has emerged as an important regulator of metabolic disorders and age-related diseases in NLRP3-deficient mice. In this article, we determine whether, in old mice C57BL6J, the NLRP3 inflammasome inhibitor MCC950 is able to attenuate age-related metabolic syndrome to providing health benefits. We report that MCC950 attenuates metabolic and hepatic dysfunction in aged mice. In addition, MCC950 inhibited the Pi3K/AKT/mTOR pathway, enhanced autophagy, and activated peroxisome proliferator-activated receptor-α in vivo and in vitro. The data suggest that MCC950 mediates the protective effects by the mammalian target of rapamycin inhibition, thus activating autophagy and peroxisome proliferator-activated receptor-α. In conclusion, pharmacological inhibition of NLRP3 in aged mice has a significant impact on health. Thus, NLRP3 may be a therapeutic target of human age-related metabolic syndrome.

Concurrent progressive multifocal leukoencephalopathy and central nervous system infiltration by multiple myeloma: A case report.

Progressive multifocal leukoencephalopathy rarely occurs in patients with multiple myeloma. Intracranial central nervous system invasion is also an uncommon event in multiple myeloma, occurring in less than 1% of cases. We describe herein an exceptional case of coexisting progressive multifocal leukoencephalopathy and intraparenchymal central nervous system myeloma infiltration. A 73-year-old woman with relapsed multiple myeloma was treated with 15 cycles of lenalidomide and dexamethasone, but therapy had to be stopped because of a hip fracture after a fall. During hospitalization, the patient developed progressive multifocal leukoencephalopathy caused by John Cunningham virus, and a prominent intra-parenchymal CD138-positive infiltrate was detected. VDJ rearrangements of the immunoglobulin heavy chain gene and the mutational profile of plasma cells in bone marrow at the time of diagnosis and in brain biopsy after progression were analyzed by next generation sequencing, showing genetic differences between medullary and extramedullary myeloma cells. The role of long-term treatment with lenalidomide and dexamethasone in the development progressive multifocal leukoencephalopathy or intraparenchymal central nervous system myeloma infiltration remains unknown. However, our results suggest that both events may have arisen as a consequence of treatment-related immunosuppression. Thus, an appropriate clinical approach compatible with the simultaneous treatment of progressive multifocal leukoencephalopathy and multiple myeloma should be developed.