A three-gene expression score for predicting clinical benefit to anti-PD-1 blockade in advanced renal cell carcinoma.

In the advanced renal cell carcinoma (RCC) scenario, there are no consistent biomarkers to predict the clinical benefit patients derived from immune checkpoint blockade (ICB). Taking this into consideration, herein, we conducted a retrospective study in order to develop and validate a gene expression score for predicting clinical benefit to the anti-PD-1 antibody nivolumab in the context of patients diagnosed with advanced clear cell RCC enrolled in the CheckMate-009, CheckMate-010, and CheckMate-025 clinical trials. First, a three-gene expression score (3GES) with prognostic value for overall survival integrating HMGA1, NUP62, and ARHGAP42 transcripts was developed in a cohort of patients treated with nivolumab. Its prognostic value was then validated in the TCGA-KIRC cohort. Second, the predictive value for nivolumab was confirmed in a set of patients from the CheckMate-025 phase 3 clinical trial. Lastly, we explored the correlation of our 3GES with different clinical, molecular, and immune tumor characteristics. If the results of this study are definitively validated in other retrospective and large-scale, prospective studies, the 3GES will represent a valuable tool for guiding the design of ICB-based clinical trials in the aRCC scenario in the near future.

The S-REAL study: Spanish real-world data on unresectable stage III NSCLC patients treated with durvalumab after chemoradiotherapy.

OBJECTIVES: The S-REAL study aimed to assess the effectiveness of durvalumab as consolidation therapy after definitive chemoradiotherapy (CRT) in a real-world cohort of patients with locally advanced, unresectable stage III non-small cell lung cancer (LA-NSCLC) included in a Spanish early access program (EAP). METHODS: In this multicentre, observational, retrospective study we analysed data from patients treated in 39 Spanish hospitals, who started intravenous durvalumab (10 mg/kg every 2 weeks) between September 2017 and December 2018. The primary endpoint was progression-free survival (PFS). Secondary endpoints included patient characterization and adverse events of special interest (AESI). RESULTS: A total of 244 patients were followed up for a median of 21.9 months [range 1.2-34.7]. Median duration of durvalumab was 45.5 weeks (11.4 months) [0-145]. Median PFS was 16.7 months (95% CI 12.2-25). No remarkable differences in PFS were observed between patients with programmed cell death-ligand 1 (PD-L1) expression ≥ 1% or < 1% (16.7 versus 15.6 months, respectively). However, PFS was higher in patients who had received prior concurrent CRT (cCRT) versus sequential CRT (sCRT) (20.6 versus 9.4 months). AESIs leading to durvalumab discontinuation were registered in 11.1% of patients. CONCLUSIONS: These results are in line with prior published evidence and confirm the benefits of durvalumab in the treatment of LA-NSCLC patients in a real-world setting. We also observed a lower incidence of important treatment-associated toxicities, such as pneumonitis, compared with the pivotal phase III PACIFIC clinical study.

ADAMTS13 recovery in acute thrombotic thrombocytopenic purpura after caplacizumab therapy.

ABSTRACT: Caplacizumab prevents the interaction between von Willebrand factor and platelets and is used to treat immune thrombotic thrombocytopenic purpura (iTTP). Its administration has been associated with a delay in ADAMTS13 activity restoration after plasma exchange (PEX) suspension. We analyzed the outcomes of 113 iTTP episodes, 75 of which were treated with caplacizumab, in 108 patients from the Spanish Registry of Thrombotic Thrombocytopenic Purpura. Caplacizumab shortened the time to platelet count normalization and reduced PEX requirement, exacerbations, and relapses. There was no difference in the time to achieve ADAMTS13 activity ≥20% after PEX end between caplacizumab-treated and nontreated episodes (median [interquartile range], 14.5 [7.7-27.2] vs 13.0 [8.0-29.0] days, P = .653). However, considering the 36 episodes in which caplacizumab was started ≤3 days after iTTP diagnosis, the time for ADAMTS13 restoration from PEX end was higher than in those episodes in which caplacizumab was started >3 days after iTTP diagnosis (20.0 [12.0-43.0] vs 11.0 [3.5-20.0] days, P = .003) or than in non-caplacizumab-treated episodes (P = .033). This finding could be related to a significantly shorter duration of PEX in early caplacizumab-treated episodes than in late caplacizumab-treated episodes (5.5 [4.0-9.0] vs 15.0 [11.0-21.5] days, P < .001) or non-caplacizumab-treated episodes (11.0 [6.0-26.0] days, P < .001). There were no differences in time to ADAMTS-13 restoration from PEX start (28.0 [17.2-47.5], 27.0 [19.0-37.5] and 29.5 [15.2-45.0] days in early caplacizumab-treated, late caplacizumab-treated and non-caplacizumab-treated episodes). Early administered caplacizumab does not prevent the requirement for immunosuppression but has beneficial effects by shortening PEX requirement without major safety concerns.

Sistema de observación para la evaluación técnica en la danza clásica: ejercicio del battement jeté / Sistema de observação paraavaliação técnica em dança clássica:exercício battement jeté / Observation system fortechnical evaluation in classical dance: battement jeté exercise

Los bailarines y las bailarinas de danza clásica entrenan rigurosamente para alcanzar el mayor grado técnico y artístico de calidad en sus ejercicios. Entre los que conforman sus entrenamientos están los de barra, siendo los battement jeté en sus diferentes formas de ejecución, los encargados del movimiento de acción de los pies-piernas. El objetivo del estudio es crear y validar una herramienta de observación ad hoc que permita evaluar el ejercicio del battement jeté; en su diseño se utilizó una combinación de formato de campo y sistemas de categorías exhaustivas y mutuamente excluyentes (E/ME). El instrumento se compone de 5 criterios y un total de 66 categorías distribuidas de la siguiente forma: 31 en tren inferior, 8 en tren superior, 13 para cabeza/mirada, 5 en dirección espacial y 9 para las cuentas musicales. La muestra del estudio estuvo conformada por 10 bailarines/as, ocho mujeres y dos hombres, todos con estudios profesionales en danza clásica finalizados. Se llevó a cabo un análisis de Calidad del Dato y un análisis de Generalizabilidad con los programas HOISAN y SAGT v1.0 respectivamente. La fiabilidad de los observadores se obtuvo mediante el cálculo de los coeficientes de correlación Pearson, Spearman y Tau b de Kendall; y mediante el índice de concordancia Kappa de Cohen y concordancia canónica de Krippendorf. Los resultados mostraron índices adecuados de correlación, así como excelentes resultados de la Generalizabilidad con un valor G relativo y G absoluto de 1.00 en el acuerdo interobservador y 1.00 para el acuerdo intraobservador, demostrando que la herramienta de observación para el ejercicio del battement jeté en la danza clásica presenta una adecuada precisión, fiabilidad y validez. Se hace un análisis de invarianza y no se evidencian diferencias significativas en los resultados por razón de sexo en el uso de la herramienta de observación. (AU)

Classical dancers train rigorously to achieve the highest technical and artistic quality in their exercises. Among those that make up his training are those of the barre, being the battement jeté in their different forms of execution, those in charge of the action movement of the feet-legs.The objective of the study is to create and validate an ad hoc observation tool that allows an evaluation of the exercise of the battement jeté; A combination of field format and exhaustive and mutually exclusive (E/ME) category systems was used in its design. The instrument is made up of 5 criteria and a total of 66 categories distributed as follows: 31 in the lower body, 8 in the upper body, 13 for head/gaze, 5 in spatial direction, and 9 for musical accounts. The studysample consisted of 10 dancers, eight women, and two men, all with completed professional studies in classical dance. A Data Quality analysis and a Generalizability analysis were carried out with the HOISAN and SAGT v1.0 programs respectively. Observer reliability was obtained by calculating the Pearson, Spearman, and Kendall's Tau b correlation coefficients; and using Cohen's Kappa concordance index and Krippendorf's canonical concordance. The results showed adequate correlation indices, as well as excellent Generalizability results with a relative G value and absolute G value of 1.00 for inter-observer agreement and 1.00 for intra-observer agreement, demonstrating that the observation tool for the battement jeté exercise in the Classical dance presents anadequate precision, reliability, and validity. An invariance analysis is made and no significant differences are found in the results due to the question of male or female gender in using the observation tool. (AU)

Os bailarinos clássicos treinam rigorosamente para atingir o mais alto grau de qualidadetécnica e artística em seus exercícios. Entre os exercícios que compõem o seu treino estão os exercícios da barra, sendo o battement jeté nas suas diferentes formas de execução, os responsáveis pelo movimento de ação dos pés-pernas. O objetivo do estudoé criar e validar uma ferramenta de observação ad hoc que permita avaliar o exercício do battement jeté. Uma combinação de formato de campo e sistemas de categoria exaustiva e mutuamente exclusiva (E/ME) foram usadas no seu design. O instrumento é composto por 5 critérios e um total de 66 categoriasdistribuídas da seguinte forma: 31 na parte inferior do corpo, 8 na parte superior do corpo, 13 para cabeça/olhar, 5 para direção espacial e 9 para contas musicais. A amostra do estudo foi composta por 10 bailarinos, sendo oito mulheres e dois homens, todos com formação profissional em dança clássica concluída. Uma análise de qualidade de dados e uma análise de generalização foram realizadas com os programas HOISAN e SAGT v1.0, respectivamente. A confiabilidadedo observador foi obtida calculando-se os coeficientes de correlação Tau b de Pearson, Spearman e Kendall e o índice de concordância Kappa de Cohen, bem como a concordância canônica de Krippendorf. Os resultados mostraram índices de correlação adequados, bem como excelentes resultados de generalização com valor de G relativo e valor de G absoluto de 1,00 para concordância interobservador e 1,00 para concordância intraobservador, demonstrando que a ferramenta de observação para o exercício battement jeté nadança clássica apresenta precisão, confiabilidade e validade adequadas. Foi ainda realiazada uma análise de invariância e não foram encontradas diferenças significativas nos resultados em função do sexo no uso da ferramenta de observação. (AU)

Usefulness of PIVKA-II for monitoring after liver transplantation in patients with hepatocellular carcinoma.

The high morbidity and mortality of hepatocellular carcinoma (HCC) has encouraged the search for new biomarkers to be used alongside alpha-foetoprotein (AFP) and imaging tests. The aim of this study was to evaluate the clinical contribution of protein induced by vitamin K absence or antagonist-II (PIVKA-II) for HCC monitoring after liver transplantation (LT) and compare it with AFP, a routinely used tumour marker. A total of 46 HCC patients (Milan criteria) were enrolled in this study. Serum levels of PIVKA-II and AFP were measured before and after transplantation. Clinical features were determined for all the patients that were included. Significant correlations were found between PIVKA-II expression levels and some clinicopathological features, such as tumour size and number of pre-transplant transarterial chemoembolizations (TACEs). Serum levels of PIVKA-II and AFP decreased significantly after LT and increased in patients with tumour recurrence. Serum PIVKA-II levels may play an important role in predicting disease severity. Furthermore, monitoring PIVKA-II levels in HCC transplant recipients reflects the tumor early recurrence after transplantation and could be used, complementing AFP and imaging tests, as a novel biomarker of this pathology.

Extracellular Vesicles' Genetic Cargo as Noninvasive Biomarkers in Cancer: A Pilot Study Using ExoGAG Technology.

The two most developed biomarkers in liquid biopsy (LB)-circulating tumor cells and circulating tumor DNA-have been joined by the analysis of extracellular vesicles (EVs). EVs are lipid-bilayer enclosed structures released by all cell types containing a variety of molecules, including DNA, mRNA and miRNA. However, fast, efficient and a high degree of purity isolation technologies are necessary for their clinical routine implementation. In this work, the use of ExoGAG, a new easy-to-use EV isolation technology, was validated for the isolation of EVs from plasma and urine samples. After demonstrating its efficiency, an analysis of the genetic material contained in the EVs was carried out. Firstly, the sensitivity of the detection of point mutations in DNA from plasma EVs isolated by ExoGAG was analyzed. Then, a pilot study of mRNA expression using the nCounter NanoString platform in EV-mRNA from a healthy donor, a benign prostate hyperplasia patient and metastatic prostate cancer patient plasma and urine samples was performed, identifying the prostate cancer pathway as one of the main ones. This work provides evidence for the value of using ExoGAG for the isolation of EVs from plasma and urine samples, enabling downstream applications of the analysis of their genetic cargo.

Atezolizumab Plus Bevacizumab as First-line Treatment for Patients With Metastatic Nonsquamous Non-Small Cell Lung Cancer With High Tumor Mutation Burden: A Nonrandomized Controlled Trial.

Importance: Antiangiogenic drug combinations with anti-programmed cell death 1 protein and anti-programmed cell death 1 ligand 1 (PD-L1) agents are a novel treatment option for lung cancer. However, survival remains limited, and the activity of these combinations for tumors with high tumor mutation burden (TMB) is unknown. Objective: To assess the clinical benefits and safety of atezolizumab plus bevacizumab for patients with high-TMB advanced nonsquamous non-small cell lung cancer (NSCLC). Design, Setting, and Participants: This multicenter, single-arm, open-label, phase 2 nonrandomized controlled trial (Atezolizumab Plus Bevacizumab in First-Line NSCLC Patients [TELMA]) included treatment-naive patients aged 18 years or older with confirmed stage IIIB-IV nonsquamous NSCLC with TMB of 10 or more mutations/megabase and no EGFR, ALK, STK11, MDM2, or ROS1 alterations. From May 2019 through January 2021, patients were assessed at 13 sites in Spain, with follow-up until February 28, 2022. Interventions: Participants were given atezolizumab, 1200 mg, plus bevacizumab, 15 mg/kg, on day 1 of each 21-day cycle. Treatment was continued until documented disease progression, unacceptable toxic effects, patient withdrawal, investigator decision, or death. Main Outcomes and Measures: The primary end point was 12-month progression-free survival (PFS) rate (according to Response Evaluation Criteria in Solid Tumours, version 1.1 criteria); PFS was defined as the time from enrollment to disease progression or death. Adverse events were monitored according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Results: A total of 307 patients were assessed for trial eligibility, of whom 266 were ineligible for enrollment. Of the 41 patients enrolled, 3 did not fulfill all inclusion criteria and were excluded. The remaining 38 patients (28 [73.7%] male; mean [SD] age, 63.7 [8.3] years) constituted the per-protocol population. The 12-month PFS rate was 51.3% (95% CI, 34.2%-66.0%), which met the primary end point. The 12-month overall survival (OS) rate was 72.0% (95% CI, 54.1%-83.9%). The median PFS was 13.0 months (95% CI, 7.9-18.0 months), and the median OS was not reached. Of the 38 patients, 16 (42.1%) achieved an objective response and 30 (78.9%) achieved disease control. The median time to response was 2.8 months (IQR, 2.8-3.58 months), with a median duration of response of 11.7 months (range, 3.57-22.4 months; the response was ongoing at cutoff). Of 16 responses, 8 (50.0%) were ongoing. Most adverse events were grade 1 or 2. For atezolizumab, the most common adverse events were fatigue (6 [15.8%]) and pruritus (6 [15.8%]). For bevacizumab, they were hypertension (10 [26.3%]) and proteinuria (4 [10.5%]). Drug discontinuation occurred in 2 patients receiving atezolizumab (5.3%) and 3 patients receiving bevacizumab (7.9%). PD-L1 levels were not associated with response, PFS, or OS. Conclusions and Relevance: These findings suggest that atezolizumab with bevacizumab is a potential treatment for high-TMB nonsquamous NSCLC. Trial Registration: ClinicalTrials.gov Identifier: NCT03836066.

Plasma cell-free DNA and circulating tumor cells as prognostic biomarkers in small cell lung cancer patients.

Background: Lack of biomarkers for treatment selection and monitoring in small cell lung cancer (SCLC) patients with the limited therapeutic options, result in poor outcomes. Therefore, new prognostic biomarkers are needed to improve their management. The prognostic value of cell-free DNA (cfDNA) and circulating tumor cells (CTCs) have been less explored in SCLC. Methods: We quantified cfDNA in 46 SCLC patients at different times during first-line of chemotherapy or chemo-immunotherapy. Moreover, CTCs were analyzed in 21 patients before therapy onset using CellSearch® system. The possible association between both biomarkers and patients' outcomes was investigated in order to develop a prognostic model. Results: High cfDNA levels before therapy were associated with shorter progression-free survival (PFS) and overall survival (OS). Furthermore, cfDNA levels at 3 weeks and at progression disease were also associated with patients' outcomes. Multivariate analyses confirmed the independence of cfDNA levels as a prognostic biomarker. Finally, the three-risk category prognostic model developed included Eastern Cooperative Oncology Group Performance Status (ECOG PS), gender and baseline cfDNA levels was associated with a higher risk of progression and death. Conclusions: We confirmed the prognostic utility of cfDNA quantitative analysis in SCLC patients before and during therapy. Our novel risk prognostic model in clinical practice will allow to identify patients who could benefit with actual therapies.

Understanding microRNAs in the Context of Infection to Find New Treatments against Human Bacterial Pathogens.

The development of RNA-based anti-infectives has gained interest with the successful application of mRNA-based vaccines. Small RNAs are molecules of RNA of <200 nucleotides in length that may control the expression of specific genes. Small RNAs include small interference RNAs (siRNAs), Piwi-interacting RNAs (piRNAs), or microRNAs (miRNAs). Notably, the role of miRNAs on the post-transcriptional regulation of gene expression has been studied in detail in the context of cancer and many other genetic diseases. However, it is also becoming apparent that some human miRNAs possess important antimicrobial roles by silencing host genes essential for the progress of bacterial or viral infections. Therefore, their potential use as novel antimicrobial therapies has gained interest during the last decade. The challenges of the transport and delivery of miRNAs to target cells are important, but recent research with exosomes is overcoming the limitations in RNA-cellular uptake, avoiding their degradation. Therefore, in this review, we have summarised the latest developments in the exosomal delivery of miRNA-based therapies, which may soon be another complementary treatment to pathogen-targeted antibiotics that could help solve the problem caused by multidrug-resistant bacteria.

Cognitive, emotional, and somatosensory behavior in professional dancers with acute and chronic pain.

BACKGROUND: Dance has been linked in a complex manner to pain and the physical and psychological peculiarities of this discipline could influence pain perception and chronicity of pain. OBJECTIVE: To determine the differences in cognitive, emotional, and somatosensory symptoms between dancers with acute versus chronic pain. DESIGN: A cross-sectional study of professional dancers with pain. SETTING: Higher conservatory of dance. PARTICIPANTS: Thirty-four professional dancers experiencing pain were included. The cohort was divided into two subgroups: those with acute pain (<3 months duration) and those with chronic pain (>3 months duration). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Pain intensity (as measured by the visual analogue scale or VAS), pressure pain threshold (PPT), Pain Catastrophizing Scale (PCS), pain-related fear of movement (Tampa Scale of Kinesiophobia [TSK-11]), fear avoidance beliefs (Fear-Avoidance Beliefs Questionnaire [FABQ]), self-efficacy (Chronic Pain Self-Efficacy Scale [CPSS]). and chronic pain severity (Chronic Pain Graded Scale [CPGS]). RESULTS: Dancers with chronic pain reported higher levels of pain intensity in daily activities (p < .01; t = 3.42; d = 1.17) and during exercise/dance (p = .02; t = 2.82; d = 0.82), as well as lower PPT in lumbar (p = .03; t = 3.22; d = 1.1) and tibialis regions (p = .01; t = 2.51; d = 0.86). Dancers with acute pain experienced worse psychological symptoms indicated by the fear of harm subscale of TSK-11 (p = .04; t = -2.08; d = 0.72), physical activity subscale of FABQ (p = .03; t = -2.27; d = 0.78), and pain management subscale of CPSS (p = .01; t = -2.76; d = 0.94) and lower scores for CPGS scale (p = .01; t = 2.99; d = 0.7 to 1.26). CONCLUSIONS: The results showed differences in pain intensity and PPT revealing higher values in dancers with chronic pain. It is possible that the physical and psychological characteristics of dancers, as well as the sociocultural aspects of this discipline, could influence the way in which this population interprets pain.

Evaluation of procalcitonin elevation during ICU stay and its relationship with mortality in ICU patients for COVID-19 with respiratory involvement. A multicenter prospective cohort study.

Introduction: A multicenter prospective cohort study studied patients admitted to the intensive care unit (ICU) by coronavirus-19 (COVID-19) with respiratory involvement. We observed the number of occasions in which the value of procalcitonin (PCT) was higher than 0.5 ng/ml. Objective: Evaluation of PCT elevation and influence on mortality in patients admitted to the ICU for COVID-19 with respiratory involvement. Measurements and main results: We studied 201 patients. On the day of admission, acute physiology and chronic health evaluation (APACHE)-II was 13 (10-16) points. In-hospital mortality was 36.8%. During ICU stay, 104 patients presented 1 or more episodes of PCT elevation and 60 (57.7%) died and 97 patients did not present any episodes of PCT elevation and only 14 (14.4%) died (p < 0.001). Multivariable analysis showed that mortality was associated with APACHE-II: [odds ratio (OR): 1.13 (1.04-1.23)], acute kidney injury [OR: 2.21 (1.1-4.42)] and with the presentation of one or more episodes of escalating PCT: [OR: 5.07 (2.44-10.53)]. Of 71 patients who died, 59.2% had an elevated PCT value on the last day, and of the 124 patients who survived, only 3.2% had an elevated PCT value on the last day (p < 0.001). On the last day of the ICU stay, the sequential organ failure assessment (SOFA) score of those who died was 9 (6-11) and 1 (0-2) points in survivors (p < 0.001). Of the 42 patients who died and in whom PCT was elevated on the last day, 71.4% were considered to have a mainly non-respiratory cause of death. Conclusion: In patients admitted to the ICU by COVID-19 with respiratory involvement, numerous episodes of PCT elevation are observed, related to mortality. PCT was elevated on the last day in more than half of the patients who died. Serial assessment of procalcitonin in these patients is useful because it alerts to situations of high risk of death. This may be useful in the future to improve the treatment and prognosis of these patients.

Clinical potential of circulating free DNA and circulating tumour cells in patients with metastatic non-small-cell lung cancer treated with pembrolizumab.

Immune checkpoint inhibitors, such as pembrolizumab, are revolutionizing therapeutic strategies for different cancer types, including non-small-cell lung cancer (NSCLC). However, only a subset of patients benefits from this therapy, and new biomarkers are needed to select better candidates. In this study, we explored the value of liquid biopsy analyses, including circulating free DNA (cfDNA) and circulating tumour cells (CTCs), as a prognostic or predictive tool to guide pembrolizumab therapy. For this purpose, a total of 109 blood samples were collected from 50 patients with advanced NSCLC prior to treatment onset and at 6 and 12 weeks after the initiation of pembrolizumab. Plasma cfDNA was measured using hTERT quantitative PCR assay. The CTC levels at baseline were also analysed using two enrichment technologies (CellSearch® and Parsortix systems) to evaluate the efficacy of both approaches at detecting the presence of programmed cell death ligand 1 on CTCs. Notably, patients with high baseline hTERT cfDNA levels had significantly shorter progression-free survival (PFS) and overall survival (OS) than those with low baseline levels. Moreover, patients with unfavourable changes in the hTERT cfDNA levels from baseline to 12 weeks showed a higher risk of disease progression. Additionally, patients in whom CTCs were detected using the CellSearch® system had significantly shorter PFS and OS than patients who had no CTCs. Finally, multivariate regression analyses confirmed the value of the combination of CTCs and cfDNA levels as an early independent predictor of disease progression, identifying a subgroup of patients who were negative for CTCs, who presented low levels of cfDNA and who particularly benefited from the treatment.

Early use of tocilizumab in patients with severe pneumonia secondary to severe acute respiratory syndrome coronavirus 2 infection and poor prognostic criteria: Impact on mortality rate and intensive care unit admission.

ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, keeps spreading globally. Evidence suggests that a subgroup of patients with severe symptomatology might have cytokine storms, which increases mortality. The use of interleukin-6 (IL-6) inhibitors may help in controlling the pathological immune response to the virus. Tocilizumab, a monoclonal antibody against IL-6, stands as an optional treatment for COVID-19 patients presenting this inflammatory hyper-response.We conducted a retrospective, observational, cohort study including 50 patients affected by COVID-19 with severe pneumonia and poor prognosis criteria, who have also undergone standard treatment; 36 of these patients additionally received tocilizumab in an early stage. The need for intensive care unit (ICU) admission, mortality, recovery of respiratory function, and improvement of biochemical and hematological parameters were compared between cohorts.Most patients were men, non-smokers and the most frequently reported comorbidities were hypertension and diabetes. Recurrent symptoms were fever, cough, and dyspnoea. 54.8% of patients from the tocilizumab group needed intubation, while in the control group 85.7% needed it. Treatment with tocilizumab significatively increased IL-6 levels, (554.45; CI 95% 186.69, 1032.93; P < .05) while C-reactive protein mean levels were reduced (-108.19; CI 95% -140.15, -75.33; P < .05), but no significant difference was found between cohorts. In comparison with the controls, tocilizumab reduced mortality (25.0% vs 42.9%, P = .021) and the number of ICU admissions (63.9% vs 100.0%, P = .021). 44.1% of patients treated with tocilizumab showed favorable radiological evolution, when compared with 15.4% of patients from the control group.Tocilizumab may improve clinical symptoms and mitigate deterioration observed in severe COVID-19 patients, and could be considered as an effective therapeutic option in subjects experiencing a significant inflammatory response to the disease.

Novel Methods to Identify Oxidative Stress-Producing Antibiotics.

Antibiotherapy is the main therapeutic strategy in the fight against bacterial pathogens. However, the misuse of antimicrobials has led to the appearance of antimicrobial-resistant strains. The rate at which we isolate multidrug-resistant bacteria is now much faster than the discovery rate of new antimicrobials. Therefore, the repurposing of approved drugs against multidrug-resistant bacteria is a very promising strategy to find new therapies against these pathogens. Some antibiotics generate oxidative stress as part of their mechanism of action. We have recently applied different methods to find new oxidative stress-producing antimicrobials with synergistic action against intracellular pathogens. Here, we detail several procedures that could be used to identify oxidative stress-producing antimicrobials with a synergistic mechanism of action.

Longitudinal CTCs gene expression analysis on metastatic castration-resistant prostate cancer patients treated with docetaxel reveals new potential prognosis markers.

CTCs have extensively been used for the monitoring and characterization of metastatic prostate cancer, but their application in the clinic is still very scarce. Besides, the resistance mechanisms linked to prostate cancer treatment remain unclear. Liquid biopsies represent the most promising alternative due to the complexity of biopsying bone metastasis and the duration of the disease. We performed a prospective longitudinal study in CTCs from 20 castration-resistant prostate cancer patients treated with docetaxel. For that, we used CellSearch® technology and a custom gene expression panel with qRT-PCR using a CTCs negative enrichment approach. We found that CTCs showed a hybrid phenotype during the disease, where epithelial features were associated with the presence of ≥ 5 CTCs/7.5 mL of blood, while high relative expression of the gene MYCL was observed preferentially in the set of samples with < 5 CTCs/7.5 mL of blood. At baseline, patients whose CTCs had stem or hybrid features showed a later progression. After 1 cycle of docetaxel, high relative expression of ZEB1 indicated worse outcome, while KRT19 and KLK3 high expression could predisposed the patients to a worse prognosis at clinical progression. In the present work we describe biomarkers with clinical relevance for the prediction of early response or resistance in castration-resistant prostate cancer patients. Besides, we question the utility of targeted isolated CTCs and the use of a limited number of markers to define the CTCs population.

Novel Treatments and Preventative Strategies Against Food-Poisoning Caused by Staphylococcal Species.

Staphylococcal infections are a widespread cause of disease in humans. In particular, S. aureus is a major causative agent of infection in clinical medicine. In addition, these bacteria can produce a high number of staphylococcal enterotoxins (SE) that may cause food intoxications. Apart from S. aureus, many coagulase-negative Staphylococcus spp. could be the source of food contamination. Thus, there is an active research work focused on developing novel preventative interventions based on food supplements to reduce the impact of staphylococcal food poisoning. Interestingly, many plant-derived compounds, such as polyphenols, flavonoids, or terpenoids, show significant antimicrobial activity against staphylococci, and therefore these compounds could be crucial to reduce the incidence of food intoxication in humans. Here, we reviewed the most promising strategies developed to prevent staphylococcal food poisoning.

Current Status and Future Perspectives of Liquid Biopsy in Small Cell Lung Cancer.

Approximately 19% of all cancer-related deaths are due to lung cancer, which is the leading cause of mortality worldwide. Small cell lung cancer (SCLC) affects approximately 15% of patients diagnosed with lung cancer. SCLC is characterized by aggressiveness; the majority of SCLC patients present with metastatic disease, and less than 5% of patients are alive at 5 years. The gold standard of SCLC treatment is platinum and etoposide-based chemotherapy; however, its effects are short. In recent years, treatment for SCLC has changed; new drugs have been approved, and new biomarkers are needed for treatment selection. Liquid biopsy is a non-invasive, rapid, repeated and alternative tool to the traditional tumor biopsy that could allow the most personalized medicine into the management of SCLC patients. Circulating tumor cells (CTCs) and cell-free DNA (cfDNA) are the most commonly used liquid biopsy biomarkers. Some studies have reported the prognostic factors of CTCs and cfDNA in SCLC patients, independent of the stage. In this review, we summarize the recent SCLC studies of CTCs, cfDNA and other liquid biopsy biomarkers, and we discuss the future utility of liquid biopsy in the clinical management of SCLC.

Robots Under COVID-19 Pandemic: A Comprehensive Survey.

As a result of the difficulties brought by COVID-19 and its associated lockdowns, many individuals and companies have turned to robots in order to overcome the challenges of the pandemic. Compared with traditional human labor, robotic and autonomous systems have advantages such as an intrinsic immunity to the virus and an inability for human-robot-human spread of any disease-causing pathogens, though there are still many technical hurdles for the robotics industry to overcome. This survey comprehensively reviews over 200 reports covering robotic systems which have emerged or have been repurposed during the past several months, to provide insights to both academia and industry. In each chapter, we cover both the advantages and the challenges for each robot, finding that robotics systems are overall apt solutions for dealing with many of the problems brought on by COVID-19, including: diagnosis, screening, disinfection, surgery, telehealth, care, logistics, manufacturing and broader interpersonal problems unique to the lockdowns of the pandemic. By discussing the potential new robot capabilities and fields they applied to, we expect the robotics industry to take a leap forward due to this unexpected pandemic.