This proof-of-concept research reports a label and bio-active free electrochemical testosterone (hormone essential regulating body function) sensing at low and in physiological range using molecularly imprinted polymers (MIPs)-based electrochemical sensing platform. State-of-the-art testosterone testing is clinical-based involving expertise, sophisticated laboratory set-up, and time-consuming testing and analysis. These consequences are limiting testosterone testing regularly suitable for an average person and a wide population. To manage these challenges, o-phenylenediamine (oPD) electropolymerized to poly(o-phenylenediamine) i.e., PoPD using cyclic voltammetry within minutes for fabricating MIP onto miniaturized screen-printed-electrode (SPE) for electrical testosterone sensing application. PoPD-MIPs/SPE sensor was responsive to varied concentrations of testosterone and exhibited a detection limit (LoD) of 1 ng/dL and a wide detection ranging from 1 to 25 ng/dL. The observed LoD correlates with the salivary testosterone of a healthy male. Therefore, PoPD-MIPs/SPE sensor, interfaced with a miniaturized potentiostat (M−P) and smartphone, has the potential of point-of-care (POC) testosterone sensing. 

Label and bio-active free electrochemical detection of testosterone hormone using MIP-based sensing platform

Aim: Report the final analysis from ASTRIS, the largest real-world study of second-/later-line osimertinib in advanced/metastatic EGFR T790M non-small-cell lung cancer (NSCLC). Methods: Patients with advanced/metastatic EGFR T790M NSCLC and prior EGFR-TKI treatment, received once-daily osimertinib 80 mg. Primary end point: overall survival (OS); secondary end points: progression-free survival (PFS), time-to-treatment discontinuation (TTD) and response rate. Safety was also recorded. Results: In 3014 patients, median OS: 22.8 months (21.6–23.8), median PFS: 11.1 months (11.0–12.0), median TTD: 13.5 months (12.6–13.9), and response rate: 57.3% (55.5–59.2). All end points reported with 95% CIs. Numerically longer median OS was observed in patients with baseline WHO performance status &lt;2 versus 2 (24.0 vs 11.1 months) and those without versus with brain/leptomeningeal metastases (25.4 vs 18.0 months). No new safety signals were identified. Conclusion: Second-/later-line osimertinib demonstrated real-world clinical benefit and safety in advanced/metastatic EGFR T790M NSCLC. Clinical Trial Registration: NCT02474355 ( ClinicalTrials.gov ) 

A real-world study of second or later-line osimertinib in patients with EGFR T790M-positive NSCLC: the final ASTRIS data

About 10% of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations are harbored as uncommon mutations. This study aimed to explore the efficacy and safety of dacomitinib, a second-generation EGFR tyrosine kinase inhibitor (EGFR-TKIs), in treating uncommon EGFR-mutated advanced NSCLC.Treatment-naïve advanced NSCLC patients treated with dacomitinib at Hunan Cancer Hospital with uncommon EGFR mutations were evaluated. The primary endpoint was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety.Between December 2019 and December 2021, a total of 16 patients was included. Median PFS was 14.0 (95% CI 4.32-23.7) months, and median OS was not reached. ORR was 68.8% (95% CI 41.3 to 89.0%) and DCR was 93.8% (95%CI 69.8 to 99.8%), including three achieving complete remission (CR) and eight achieving partial remission (PR). Median PFS for patients with brain metastasis was 9.0 (95%CI 6.9 to 11.1) months. Intracranial ORR was 100%, including 2 CR and 4 PR. Major treatment-related adverse events (TRAEs) included rash (87.5%), paronychia (62.5%), oral ulcers (50.0%), and diarrhea (50.0%), none of which were ≥ grade 3 TRAEs.Dacomitinib showed good activity and manageable toxicity in NSCLC patients with uncommon EGFR mutations. 

Efficacy and safety of dacomitinib in treatment-naïve patients with advanced NSCLC harboring uncommon EGFR mutation: an ambispective cohort study

The emerging field of liquid biopsy has garnered significant interest in precision diagnostics, offering a non-invasive and repetitive method for analyzing bodily fluids to procure real-time diagnostic data. The precision and accuracy offered by the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (CRISPR/Cas) technology have advanced and broadened the applications of liquid biopsy. Significantly, when combined with swiftly advancing nanotechnology, CRISPR/Cas-mediated nanodevices show vast potential in precise liquid biopsy applications. However, persistent challenges are still associated with off-target effects, and the current platforms also constrain the performance of the assays. In this review, we highlight the merits of CRISPR/Cas systems in liquid biopsy, tracing the development of CRISPR/Cas systems and their current applications in disease diagnosis particularly in liquid biopsies. We also outline ongoing efforts to design nanoscale devices with improved sensing and readout capabilities, aiming to enhance the performance of CRISPR/Cas detectors in liquid biopsy. Finally, we identify the critical obstacles hindering the widespread adoption of CRISPR/Cas liquid biopsy and explore potential solutions. This feature article presents a comprehensive overview of CRISPR/Cas-mediated liquid biopsies, emphasizing the progress in integrating nanodevices to improve specificity and sensitivity. It also sheds light on future research directions in employing nanodevices for CRISPR/Cas-based liquid biopsies in the realm of precision medicine.

CRISPR/Cas detection with nanodevices: moving deeper into liquid biopsy.

To investigate the effectiveness of linezolid and vancomycin for the treatment of nosocomial infections in children under 12 years old.This is a systematic review in which five randomized clinical trials about the effectiveness of linezolid and vancomycin, involving a total of 429 children with nosocomial infections, were evaluated. They were searched in scientific databases: PubMed, Bvs, and SciELO.The main nosocomial infections that affected children were bacteremia, skin, and soft tissue infections followed by nosocomial pneumonia. Most infections were caused by Gram-positive bacteria, which all studies showed infections caused by Staphylococcus aureus, with methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci strains being isolated. Both linezolid and vancomycin showed high therapeutic efficacy against different types of nosocomial infections, ranging from 84.4% to 94% for linezolid and 76.9% to 90% for vancomycin. Patients receiving linezolid had lower rates of rash and red man syndrome compared to those receiving vancomycin. However, despite the adverse reactions, antimicrobials can be safely administered to children to treat nosocomial infections caused by resistant Gram-positive bacteria.Both linezolid and vancomycin showed good efficacy in the treatment of bacterial infections caused by resistant Gram-positive bacteria in hospitalized children. However, linezolid stands out regarding its pharmacological safety. Importantly, to strengthen this conclusion, further clinical trials are needed to provide additional evidence. 

Linezolid and vancomycin for nosocomial infections in pediatric patients: a systematic review

The capability to monitor doping in a rapid and sensitive manner is highly promising in the field of doping control.

Rapid and ultra-sensitive testosterone detection via aptamer-functional gold nanoparticles

Catalytic hairpin assembly-assisted dual-signal amplification platform for ultrasensitive detection of tumor markers and intelligent diagnosis of gastric cancer.

A label-free fluorescence resonance energy transfer (FRET) platform based on cationic conjugated polymers and aptamers for ultrasensitive and specific ractopamine detection was constructed. This method exhibited a wide linear range from 0.05 to 500 μM and a low limit of detection of 47 nM, which make it an attractive assay platform for foodborne doping.

https://pubs.rsc.org/en/content/articlepdf/2022/ra/d2ra00574c

Cationic conjugated polymer-based FRET aptasensor for label-free and ultrasensitive ractopamine detection

Correction for ‘Cationic conjugated polymer-based FRET aptasensor for label-free and ultrasensitive ractopamine detection’ by Xuancheng Fu et al., RSC Adv., 2022, 12, 10911–10914, https://doi.org/10.1039/d2ra00574c.

Correction: Cationic conjugated polymer-based FRET aptasensor for label-free and ultrasensitive ractopamine detection

To characterize the population of critically ill patients and infections treated with linezolid in the intensive care unit (ICU), and to evaluate the clinical efficacy and safety of linezolid therapy.This multi-center, observational, real-world study was conducted across 52 hospitals between June 9, 2018, and December 28, 2019. Patients who met the following inclusion criteria were included: (1) admitted to the ICU, (2) of any age group, and (3) having a clinical or laboratory diagnosis of a Gram-positive bacterial infection. Clinical efficacy was categorized as success (cured or improved), failed, or non-evaluable. Adverse events and serious adverse events were recorded during treatment.A total of 366 ICU patients who met the inclusion criteria were evaluated. Linezolid was used as second- and first-line treatment in 232 (63.4%) and 134 (36.6%) patients, respectively. The most common isolated strain was Staphylococcus aureus (methicillin-resistant Staphylococcus aureus: n=37/119, 31.1%; methicillin-susceptible Staphylococcus aureus: n=15/119, 12.6%); this was followed by Enterococci (vancomycin-resistant Enterococci: n=8/119, 6.7%; vancomycin-susceptible Enterococci: n=11/119, 9.2%) and Streptococcus pneumoniae (multidrug-resistant: n=4/119, 3.4%; non-multidrug resistant: n=2/119, 1.7%). The main infection sites where pathogens were detected included the lung (n=216/366, 59.6%), skin and soft tissue (n=104/366, 28.4%), and blood (n=50/366, 13.7%). Clinical success was achieved in 301 (82.2%) patients; 34 (9.3%) were cured and 267 (73.0%) improved; treatment failure and non-evaluable outcomes were observed in 29 (7.9%) in 36 (9.8%) patients, respectively. Linezolid-related adverse events were reported in 8 (2.2%) patients. No treatment-related serious adverse events were reported.Based on real-world results, linezolid was found to be effective and safe in the treatment of Gram-positive bacterial infections in critically ill patients. 

https://doi.org/10.1016/j.jointm.2022.05.006

Clinical efficacy and safety of linezolid in intensive care unit patients

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