Advances in biomarkers, targeted therapies, and immuno-oncology have transformed the clinical management of patients with advanced NSCLC. For oncogene-driven tumors, there are highly effective ...targeted therapies against EGFR, ALK, ROS1, BRAF, TRK, RET, and MET. In addition, investigational therapies for KRAS, NRG1, and HER2 have shown promising results and may become standard-of-care in the near future. In parallel, immune-checkpoint therapy has emerged as an indispensable treatment modality, especially for patients lacking actionable oncogenic drivers. While PD-L1 expression has shown modest predictive utility, biomarkers for immune-checkpoint inhibition in NSCLC have remained elusive and represent an area of active investigation. Given the growing importance of biomarkers, optimal utilization of small tissue biopsies and alternative genotyping methods using circulating cell-free DNA have become increasingly integrated into clinical practice. In this review, we will summarize the current landscape and emerging trends in precision medicine for patients with advanced NSCLC with a special focus on predictive biomarker testing.
Rapid, low-cost, species-specific diagnosis, based upon DNA testing, is becoming important in the treatment of patients with infectious diseases. Here, we demonstrate an innovation that uses origami ...to enable multiplexed, sensitive assays that rival polymerase chain reactions (PCR) laboratory assays and provide high-quality, fast precision diagnostics for malaria. The paper-based microfluidic technology proposed here combines vertical flow sample-processing steps, including paper folding for whole-blood sample preparation, with an isothermal amplification and a lateral flow detection, incorporating a simple visualization system. Studies were performed in village schools in Uganda with individual diagnoses being completed in <50 min (faster than the standard laboratory-based PCR). The tests, which enabled the diagnosis of malaria species in patients from a finger prick of whole blood, were both highly sensitive and specific, detecting malaria in 98% of infected individuals in a double-blind first-in-human study. Our method was more sensitive than other field-based, benchmark techniques, including optical microscopy and industry standard rapid immunodiagnostic tests, both performed by experienced local healthcare teams (which detected malaria in 86% and 83% of cases, respectively). All assays were independently validated using a real-time double-blinded reference PCR assay. We not only demonstrate that advanced, low-cost DNA-based sensors can be implemented in underserved communities at the point of need but also highlight the challenges associated with developing and implementing new diagnostic technologies in the field, without access to laboratories or infrastructure.
The last decade has seen dramatic progress in the principle, design, and fabrication of photonic nanomaterials with various optical properties and functionalities. Light‐emitting and light‐responsive ...nanomaterials, such as semiconductor quantum dots, plasmonic metal nanoparticles, organic carbon, and polymeric nanomaterials, offer promising approaches to low‐cost and effective diagnostic, therapeutic, and theranostic applications. Reasonable endeavors have begun to translate some of the promising photonic nanomaterials to the clinic. Here, current research on the state‐of‐the‐art and emerging photonic nanomaterials for diverse biomedical applications is reviewed, and the remaining challenges and future perspectives are discussed.
Photonic nanomaterials are extensively investigated for various biomedical applications with the advantages of their small size, unique optical properties, and multiple functionalities. An in‐depth overview of the current state‐of‐the‐art research on multifunctional photonic nanomaterials is provided to elucidate their potential in diagnostic, therapeutic, and theranostic applications with perspectives on the foreseeable challenges toward a new era of futuristic nanomedicines.
Bloodstream infections are a major cause of death with increasing incidence and severity. Blood cultures are still the reference standard for microbiological diagnosis, but are rather slow. Molecular ...methods can be used as add-on complementary assays. They can be useful to speed up microbial identification and to predict antimicrobial susceptibility, applied to direct blood samples or positive blood cultures.
To review recent developments in molecular-based diagnostic platforms used for the identification of bloodstream infections, with a focus on assays performed directly on blood samples and positive blood cultures.
Peer reviewed articles, conference abstracts, and manufacturers' websites.
We give an update on recent developments of molecular methods in diagnosing BSIs. We first describe the currently available molecular methods to be used for positive blood cultures including: a) in situ hybridization-based methods; b) DNA-microarray-based hybridization technology; c) nucleic acid amplification-based methods; and d) combined methods. Subsequently, molecular methods applied directly to whole blood samples are discussed, including the use of nucleic acid amplification-based methods, T2 magnetic resonance-based methods, and metagenomics for diagnosing BSIs.
Advances in molecular-based methods complementary to conventional blood culture diagnostics and antimicrobial stewardship programmes may optimize infection management by allowing rapid identification of pathogens and relevant antimicrobial resistance genes. Rapid diagnosis of the causing microorganism and relevant resistance determinants is important for early administration and modification of appropriate antimicrobial therapy. Ultimately, this may lead to improved quality and cost-effectiveness of health care, as well as reduced antimicrobial resistance selection.
The vortex fluidic device accelerated immunoblot assay (VAIA) is a new method that reduces immunoblot processing time from nearly 2 h to less than 5 min. In their Communication (e202202021), Gregory ...A. Weiss and co‐workers demonstrate the broad applicability and potential of VAIA. In the picture, the artistic interpretation of VAIA demonstrates how the unique thin film microfluidics of the vortex fluidic device can accelerate immunoblot processing.
Background
In settings where both Plasmodium vivax and Plasmodium falciparum infection cause malaria, rapid diagnostic tests (RDTs) need to distinguish which species is causing the patients' ...symptoms, as different treatments are required. Older RDTs incorporated two test lines to distinguish malaria due to P. falciparum, from malaria due to any other Plasmodium species (non‐falciparum). These RDTs can be classified according to which antibodies they use: Type 2 RDTs use HRP‐2 (for P. falciparum) and aldolase (all species); Type 3 RDTs use HRP‐2 (for P. falciparum) and pLDH (all species); Type 4 use pLDH (fromP. falciparum) and pLDH (all species).
More recently, RDTs have been developed to distinguish P. vivax parasitaemia by utilizing a pLDH antibody specific to P. vivax.
Objectives
To assess the diagnostic accuracy of RDTs for detecting non‐falciparum or P. vivax parasitaemia in people living in malaria‐endemic areas who present to ambulatory healthcare facilities with symptoms suggestive of malaria, and to identify which types and brands of commercial test best detect non‐falciparum and P. vivax malaria.
Search methods
We undertook a comprehensive search of the following databases up to 31 December 2013: Cochrane Infectious Diseases Group Specialized Register; MEDLINE; EMBASE; MEDION; Science Citation Index; Web of Knowledge; African Index Medicus; LILACS; and IndMED.
Selection criteria
Studies comparing RDTs with a reference standard (microscopy or polymerase chain reaction) in blood samples from a random or consecutive series of patients attending ambulatory health facilities with symptoms suggestive of malaria in non‐falciparum endemic areas.
Data collection and analysis
For each study, two review authors independently extracted a standard set of data using a tailored data extraction form. We grouped comparisons by type of RDT (defined by the combinations of antibodies used), and combined in meta‐analysis where appropriate. Average sensitivities and specificities are presented alongside 95% confidence intervals (95% CI).
Main results
We included 47 studies enrolling 22,862 participants. Patient characteristics, sampling methods and reference standard methods were poorly reported in most studies.
RDTs detecting 'non‐falciparum' parasitaemia
Eleven studies evaluated Type 2 tests compared with microscopy, 25 evaluated Type 3 tests, and 11 evaluated Type 4 tests. In meta‐analyses, average sensitivities and specificities were 78% (95% CI 73% to 82%) and 99% (95% CI 97% to 99%) for Type 2 tests, 78% (95% CI 69% to 84%) and 99% (95% CI 98% to 99%) for Type 3 tests, and 89% (95% CI 79% to 95%) and 98% (95% CI 97% to 99%) for Type 4 tests, respectively. Type 4 tests were more sensitive than both Type 2 (P = 0.01) and Type 3 tests (P = 0.03).
Five studies compared Type 3 tests with PCR; in meta‐analysis, the average sensitivity and specificity were 81% (95% CI 72% to 88%) and 99% (95% CI 97% to 99%) respectively.
RDTs detecting P.vivax parasitaemia
Eight studies compared pLDH tests to microscopy; the average sensitivity and specificity were 95% (95% CI 86% to 99%) and 99% (95% CI 99% to 100%), respectively.
Authors' conclusions
RDTs designed to detect P. vivax specifically, whether alone or as part of a mixed infection, appear to be more accurate than older tests designed to distinguish P. falciparum malaria from non‐falciparum malaria. Compared to microscopy, these tests fail to detect around 5% ofP. vivax cases. This Cochrane Review, in combination with other published information about in vitro test performance and stability in the field, can assist policy‐makers to choose between the available RDTs.
12 April 2019
No update planned
Review superseded
This Cochrane Review has been superseded by Choi 2019 https://doi.org/10.1002/14651858.CD013218
G-quadruplexes constitute a unique class of nucleic acid structures formed by G-rich oligonucleotides of DNA- or RNA-type. Depending on their chemical nature, loops length, and localization in the ...sequence or structure molecularity, G-quadruplexes are highly polymorphic structures showing various folding topologies. They may be formed in the human genome where they are believed to play a pivotal role in the regulation of multiple biological processes such as replication, transcription, and translation. Thus, natural G-quadruplex structures became prospective targets for disease treatment. The fast development of systematic evolution of ligands by exponential enrichment (SELEX) technologies provided a number of G-rich aptamers revealing the potential of G-quadruplex structures as a promising molecular tool targeted toward various biologically important ligands. Because of their high stability, increased cellular uptake, ease of chemical modification, minor production costs, and convenient storage, G-rich aptamers became interesting therapeutic and diagnostic alternatives to antibodies. In this review, we describe the recent advances in the development of G-quadruplex based aptamers by focusing on the therapeutic and diagnostic potential of this exceptional class of nucleic acid structures.
STUDY DESIGN.Cross-sectional study.
OBJECTIVE.To explore the underlying anatomy of May-Thurner syndrome (MTS) using computed tomography (CT) and discuss its clinical significance for typing ...diagnosis.
SUMMARY OF BACKGROUND DATA.Because the anatomical position of the corpse cannot fully illustrate the actual clinical situation in vivo, the diversity of MTS has not been fully elucidated yet.
METHODS.We retrospectively analyzed the data of 69 patients with MTS. By CT showing, patients were categorized to simple MTS (sMTS, 22 patients), lumbar degeneration-related MTS (dMTS, 33 patients) and other causes MTS (oMTS, 14 patients); meanwhile, a healthy control group were set. Evaluated indexes were onset age, course of disease, diameter of the iliac vein tunnel (IVTD), lumbar degeneration-related iliac vein compression (IVC), therapeutic effect, and diagnostic cutoff of risk IVTD prone to MTS.
RESULTS.The onset age of sMTS, dMTS, and oMTS were respectively 42.3 ± 6.5 years, 61.5 ± 10.6 years, and 53.1 ± 16.8 years (P < 0.001); courses were respectively 12.1 ± 9.2 days, 22.5 ± 7.6 days, and 6.8 ± 6.7 days (P = 0.002). IVTDs of sMTS, dMTS, oMTS, and the control were respectively 2.52 ± 0.50 mm, 2.29 ± 0.30 mm, 5.93 ± 2.21 mm, and 4.34 ± 1.61 mm (P < 0.001). Lumbar degeneration-related IVC in dMTS occurred at 41 places, including forward bulging or protruding intervertebral discs (51%,17/33), osteophytes (50%,16/33), and spondylolisthesis (19%, 8/33), but none happened in sMTS, oMTS, and the control. Eighty-six percent of sMTSs, 55% dMTSs, and none oMTSs needed intravenous stent-implanted operation to obtain effective treatment. MTS type (Waldχ = 6.092, P = 0.009), course (Waldχ = 4.618, P = 0.032), and treatment plan (Waldχ = 14.748, P < 0.001) markedly influence the therapeutic result. The cutoff of risk IVTD for sMTS and dMTS was 2.98 mm, which diagnostic sensitivity was 90% and specificity 100%.
CONCLUSION.Owing to the distinct pathoanatomy and causes, diagnosis in classification of MTS by CT is helpful in accurate treatment program.Level of Evidence3
•The recently published Dutch protocol advises to make use of additional diagnostics in case of MCS<6mm.•Most Dutch surgeons are not aware of this protocol and do not make use of it.•Most Dutch ...surgeons treat type B fibula fractures surgically, even with no proven medial injury. This will lead to unnecessary surgery.•There is no consensus in treatment nor diagnostics of type B fibula fractures in the Netherlands. The current protocol is not being followed.
In isolated Weber B fractures (type B fibular fractures), ruling out instability is critical for safe conservative treatment. In fractures without evident medial injury, additional diagnostics like MRI scan or gravity stress test should be done to differentiate between a stable and unstable fracture. The aim of the current study is to gain more insight in current practice and treatment of type B fractures by Dutch trauma- and orthopaedic surgeons.
In December 2017 and January 2018, 559 trauma surgeons were invited by email to join an online survey. This survey consisted of questions regarding diagnostics and treatment of isolated distal fibula fractures. Also, respondents were asked to state their preferred treatment of eight separate cases.
In total, 161 surgeons participated, covering 68 different hospitals in the Netherlands. Of them, 32.0% treat more than 30 ankle fractures a year. Based on regular mortise radiographs, 13.6% of the respondents chose surgical treatment in case of a medial clear space (MCS) > 4 mm, 33.8% in case of a MCS > 6 mm and 45.5% in case of a MCS > 4 mm in addition to the MCS ≥ superior clear space + 1 mm. Moreover, 18.2% make use of additional diagnostics (43.9% repeat mortise view after a week, 16.6% weight bearing radiograph, 8.6% gravity stress view, 7.9% exorotation radiograph, 6.5% MRI scan, 0.7% ultrasound, 16.8% other) and 8% establishes their decision not based on the mortise radiograph. Fibular dislocation of ≥ 2 mm was used as an indication for surgical treatment by 69%. Of them, 56% decides to treat surgically in these cases, even with proven medial stability.
Many surgeons treat type B fibular fractures with a MCS > 4 mm at mortise view surgically, even without proven medial injury. Rarely, additional diagnostics as MRI or gravity stress test are performed in cases with a MCS 4–6 mm. Consequently many stable ankle fractures are treated operatively unnecessarily.
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