Empirical antibiotic therapy improves outcomes in mechanically ventilated patients with COVID-19: An emulated targeted trial within a prospective, multicentre cohort study.

Background: Bacterial pulmonary superinfections develop in a substantial proportion of mechanically ventilated COVID-19 patients and are associated with prolonged mechanical ventilation requirements and an increased mortality. Albeit recommended, evidence supporting the use of empirical antibiotics at intubation is weak and of low quality. The aim of this study was to elucidate the effect of empirical antibiotics, administered within 24hours of endotracheal intubation, on superinfections, duration of mechanical ventilation, and mortality in mechanically ventilated patients with COVID-19.

The effect on the performance of a dynamic navigation system of superimposing a standard tessellation language (STL) file obtained with an intraoral scan on a cone beam computer tomograph (CBCT). An experimental in vitro study.

Objectives: To compare the accuracy and operative time of implant placement using a dynamic computer assisted implant surgery (dCAIS) system based on a cone beam computer tomography (CBCT) image, with and without superimposing a standard tessellation language (STL) file of an intraoral scan of the patient.

Methods: Ten identical resin models simulating an upper maxilla with posterior edentulism were assigned to two groups. In the CBCT+STL group, a CBCT file and an intraoral STL file were superimposed and used for registration; in the CBCT group, registration was performed using CBCT images.

A Randomized Clinical Trial to Evaluate the Efficacy of an Oral Probiotic in Acne Vulgaris.

The relevance of the gut microbiota in some skin inflammatory diseases, including acne vulgaris, has been emphasized. Probiotics could play a role in the modulation of the microbiota, improving the clinical course of this disease. A 12-week randomized, double-blind, placebo-controlled, clinical trial with patients aged 12 to 30 years with acne vulgaris was conducted.

Edoxaban Versus Low-Molecular-Weight Heparin in Hospitalized COVID-19 Patients With Atrial Fibrillation.

Objective: During the first wave of the SARS-CoV-2 pandemic, management of anticoagulation therapy in hospitalized patients with atrial fibrillation (AF) was simplified to low-molecular-weight heparin (LMWH) followed by oral anticoagulation, mainly owing to the risk of drug-drug interactions. However, not all oral anticoagulants carry the same risk.

Methods: Observational, retrospective, and multicenter study that consecutively included hospitalized patients with AF anticoagulated with LMWH followed by oral anticoagulation or edoxaban concomitantly with empirical COVID-19 therapy.

Cross-cultural adaptation and validation of the Recognizing And Addressing Limited Pharmaceutical Literacy (RALPH) interview guide in community pharmacies.

Background: The RALPH (Recognizing and Addressing Limited PHarmaceutical Literacy) interview guide makes it possible to identify patients with limited pharmaceutical knowledge and to assess their skills in the functional, communicative, and critical health literacy domains.

Objective: (s): To perform a cross-cultural validation of the RALPH interview guide in Spanish population; to conduct a descriptive analysis based on patients' responses.

Methods: A cross-sectional study of patients' pharmaceutical literacy skills was conducted in three stages: systematic translation, administration of the interview and analysis of psychometric properties.

Accuracy of dental implant placement with or without the use of a dynamic navigation assisted system: A randomized clinical trial.

Objectives: To assess dental implant placement accuracy with a dynamic computer-assisted implant surgery (dCAIS) system and a freehand approach. Secondarily, to compare the patients' perception and quality of life (QoL) with the two approaches.

Methods: A double-arm randomized clinical trial was conducted.

A history of adjustment disorder predicts greater weight loss after sleeve gastrectomy.

Background: Bariatric surgery is one of the most effective long-term options for treating class III obesity or class II obesity with medical co-morbidities; however, a significant number of patients do not achieve the expected weight loss. New studies are needed to find the predictive value of different variables on surgery outcomes.

Objectives: Our aim was to study a number of physical, medical, and psychopathological variables as potential risk factors for poor outcomes in patients with class II-IV obesity scheduled for sleeve gastrectomy.

BRCA1 Expression and Outcome in Patients With -Mutant NSCLC Treated With Gefitinib Alone or in Combination With Olaparib.

Introduction: DNA repair capacity, as exemplified by gene expression, is related with outcome to EGFR tyrosine kinase inhibitors in patients with -mutant NSCLC. Olaparib, a PARP inhibitor, reduces BRCA1 expression. Olaparib was tested in combination with gefitinib versus gefitinib single agent, as a first-line therapy for patients with -mutant NSCLC in the GOAL study (trial registration: NCT01513174).

Combined FGFR and Akt pathway inhibition abrogates growth of FGFR1 overexpressing EGFR-TKI-resistant NSCLC cells.

EGFR tyrosine kinase inhibitor (TKI) resistance in non-small cell lung cancer (NSCLC) patients is inevitable. Identification of resistance mechanisms and corresponding targeting strategies can lead to more successful later-line treatment in many patients. Using spectrometry-based proteomics, we identified increased fibroblast growth factor receptor 1 (FGFR1) expression and Akt activation across erlotinib, gefitinib, and osimertinib EGFR-TKI-resistant cell line models.

Unmet Needs in the Osteoarthritis Chronic Moderate to Severe Pain Management in Spain: A Real Word Data Study.

Introduction: Patients with moderate or severe pain due to osteoarthritis (OAP) usually undergo pharmacological treatment with NSAIDs and/or opioids. Many of them do not get adequate pain relief because of intolerances, contraindications and the ineffectiveness of these treatments. The main objective of the present study was to quantify the group of OAP patients who are inadequately treated for their pain in routine clinical practice in Spain and to describe the prescription flow of these patients.

Development and Validation of the Hospital Outpatients' Information Needs Questionnaire (HOINQ).

Purpose: The main objective was to develop and validate a "Hospital Outpatients' Information Needs Questionnaire" (HOINQ). Secondly, to identify patients' preferred sources of information. Finally, to establish differences depending on the disease, as well as between sociodemographic and clinical variables.

Correction to: The Present and Future of Liquid Biopsies in Non-Small Cell Lung Cancer: Combining Four Biosources for Diagnosis, Prognosis, Prediction, and Disease Monitoring.

The original version of this review article unfortunately contained a mistake in the Funding section.

Osimertinib and dihydroartemisinin: a novel drug combination targeting head and neck squamous cell carcinoma.

Background: Recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) has a dismal prognosis with limited progression-free survival and overall survival, even when treated with different combinations of chemotherapy, targeted therapies and immunotherapy. We explored and the effect of the epidermal growth factor receptor (EGFR) inhibitor, osimertinib, alone and in combination with dihydroartemisinin (DHA) in HNSCC.

Methods: The combination of osimertinib with DHA was tested in the FaDu and CAL27 HNSCC cell lines.

Evolution and Clinical Impact of EGFR Mutations in Circulating Free DNA in the BELIEF Trial.

Introduction: Longitudinal evaluation of mutations in blood samples was a prespecified secondary objective in the BELIEF trial of erlotinib and bevacizumab in advanced EGFR-positive NSCLC. Here, we report the testing results and explore the correlation of EGFR status in blood with clinical outcomes.

Methods: Blood samples were prospectively collected from patients at baseline, at response evaluation, and at progression and sent to a central laboratory.

Osimertinib and pterostilbene in EGFR-mutation-positive non-small cell lung cancer (NSCLC).

Monotherapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) still leads to incomplete responses in most EGFR-mutation positive non-small cell lung cancer (NSCLC) patients, often due to acquired resistance through activation of parallel compensatory pathways. We have previously shown that co-targeting EGFR, signal transducer and activator of transcription 3 (STAT3), and Src-yes-associated protein 1 (YAP1) was highly synergistic in vitro and in vivo. In the present study, we treated EGFR-mutation positive cell lines with the combination of osimertinib plus a natural compound, pterostilbene, which has been reported to abrogate Src and STAT3 activation.

Targeting PKCι-PAK1 in EGFR-mutation positive non-small cell lung cancer.

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) induce significant responses in EGFR-mutation positive non-small cell lung cancer (NSCLC). However, universal progression is observed.

Methods: The effect of the anti-rheumatoid agent, auranofin, a selective inhibitor of oncogenic protein kinase C iota (PKCι) signaling and IPA-3, a non-ATP competitive p21-activated kinase 1 (PAK1) inhibitor in treatment-naïve and EGFR TKI-resistant EGFR-mutation positive NSCLC cell lines was investigated.

Mutations Classes I, II, and III in NSCLC Patients Included in the SLLIP Trial: The Need for a New Pre-Clinical Treatment Rationale.

V600 mutations have been found in 1-2% of non-small-cell lung cancer (NSCLC) patients, with Food and Drug Administration (FDA) approved treatment of dabrafenib plus trametinib and progression free survival (PFS) of 10.9 months. However, 50-80% of mutations in lung cancer are non-V600, and can be class II, with intermediate to high kinase activity and RAS independence, or class III, with impaired kinase activity, upstream signaling dependence, and consequently, sensitivity to receptor tyrosine kinase (RTK) inhibitors.

Prospective detection of mutations in cerebrospinal fluid, pleural effusion, and ascites of advanced cancer patients to guide treatment decisions.

Many advanced cases of cancer show central nervous system, pleural, or peritoneal involvement. In this study, we prospectively analyzed if cerebrospinal fluid (CSF), pleural effusion (PE), and/or ascites (ASC) can be used to detect driver mutations and guide treatment decisions. We collected 42 CSF, PE, and ASC samples from advanced non-small-cell lung cancer and melanoma patients.

Profile of alectinib for the treatment of ALK-positive non-small cell lung cancer (NSCLC): patient selection and perspectives.

Discovered in 2007, anaplastic lymphoma kinase (ALK) gene rearrangements positive (ALK+) lung cancers compose a small subset of non-small cell lung cancer (NSCLC), with rapidly expanded treatments. There are currently several ALK inhibitors, including crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib which have been licensed by the US Food and Drug Administration or the European Medicines Agency for the treatment of ALK+ NSCLC patients. Along with the multiple therapies, the survival of this subtype of NSCLC has been significantly expanded, even for patients whose disease has spread in the brain.

Safety and Efficacy of Crizotinib in Patients With Advanced or Metastatic ROS1-Rearranged Lung Cancer (EUCROSS): A European Phase II Clinical Trial.

Introduction: ROS1 rearrangements are found in 1% of lung cancer patients. Therapeutic efficacy of crizotinib in this subset has been shown in early phase trials in the United States and East Asia. Here we present data on efficacy and safety of a prospective phase II trial evaluating crizotinib in European ROS1-positive patients (EUCROSS).

Cancer Stem Cell Biomarkers in EGFR-Mutation-Positive Non-Small-Cell Lung Cancer.

Introduction: Epidermal growth factor receptor (EGFR) pathway deregulation promotes the acquisition of stemlike properties in non-small-cell lung cancer. EGFR inhibition through NOTCH enriches lung cancer stem cells (CSCs). Src through Yes-associated protein 1 (YAP1) activates NOTCH.

EGFR first- and second-generation TKIs-there is still place for them in -mutant NSCLC patients.

Identification of epidermal growth factor receptor (EGFR) as a molecular target has radically changed the treatment of metastatic non-small cell lung cancer (NSCLC) from standard chemotherapy to personalized, targeted therapy. First-, second- and third-generation EGFR tyrosine kinase inhibitors (TKIs) are now available for the treatment of EGFR-mutant NSCLC patients. This review will focus on the clinical development of first- and second-generation EGFR TKIs.

Prospective analysis of liquid biopsies of advanced non-small cell lung cancer patients after progression to targeted therapies using GeneReader NGS platform.

Background: In a significant percentage of advanced non-small cell lung cancer (NSCLC) patients, tumor tissue is unavailable or insufficient for genetic analyses at time to progression. We prospectively analyzed the appearance of genetic alterations associated with resistance in liquid biopsies of advanced NSCLC patients progressing to targeted therapies using the NGS platform.

Methods: A total of 24 NSCLC patients were included in the study, 22 progressing to tyrosine kinase inhibitors and two to other treatments.

Challenges and unanswered questions for the next decade of immune-oncology research in NSCLC.

Over the last 20 years there have been great advances in the treatment of lung cancer. Immune checkpoint blockade together with targeted therapies have provided oncologists with the means to improve survival of non-small cell lung cancer (NSCLC) and patients with a better quality of life and therapies with manageable toxicity. Maybe in a short period of time the possibility of a cure in metastatic NSCLC will be raised.

Integrin-linked kinase (ILK) and src homology 2 domain-containing phosphatase 2 (SHP2): Novel targets in EGFR-mutation positive non-small cell lung cancer (NSCLC).

Background: The activation of multiple signaling pathways jeopardizes the clinical efficacy of EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutation positive non-small cell lung cancer (NSCLC). Integrin-linked kinase (ILK) regulates the interactions between tumor cells and extracellular environment to activate signaling pathways and promote cell proliferation, migration, and epithelial-mesenchymal transition. Src homology 2 domain-containing phosphatase 2 (SHP2) is essential for receptor tyrosine kinase signaling and mitogen-activated protein kinase (MAPK) pathway activation.