Conventional Diagnostics Research Articles

P394 Evaluation of diagnostic potential of recombinant secretory aspartyl proteinase 2 (Sap2) protein from Candida parapsilosis for use in systemic candidiasis

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM ObjectivesSystemic candidiasis is the fourth most common bloodstream infection in ICU patients worldwide. Along with Candida albicans, infections caused by non-albicans Candida (NAC) species are increasingly becoming more prevalent globally along with the emergence of drug resistance. The diagnosis of systemic candidiasis is difficult due to the absence of significant clinical symptoms in patients. Since conventional diagnostics methods for candidiasis show less sensitivity and specificity, novel immunodiagnostic techniques are needed for early diagnosis. We investigated the diagnostic potential of recombinant secreted aspartyl proteinase 2 (rSap2) from C. parapsilosis for the detection of Candida infection.MethodsGenomic DNA was isolated from C. parapsilosis, followed by PCR amplification of Sap2 gene using designed gene-specific primers. Sap2 protein expression and purification was performed using Ni-NTA affinity chromatography under denaturing conditions. The denatured protein was subsequently refolded using a multi-step dialysis procedure. CD and FTIR studies were performed to confirm refolding. Mice were immunized with rSap2 protein and serum ELISA assays were performed for testing immunogenicity. Immunoblotting assays and human serum ELISAs were performed using whole-cell Candida and rSap2 protein in proven systemic candidiasis patient serum and controls, recruited at PGIMER, Chandigarh.ResultsSap2 protein from C. parapsilosis was successfully cloned and expressed using an E. coli-based prokaryotic expression system. Protein refolding was performed in vitro using step-wise dialysis. Structural analysis by CD and FTIR spectroscopy revealed the refolded protein to be in its near native conformation. Immunogenicity analysis demonstrated the rSap2 protein to be highly immunogenic as evident from significantly high titers of Sap2-specific antibodies in antigen immunized BALb/c mice, compared to sham-immunized controls. The diagnostic potential of rSap2 protein was evaluated using immunoblotting and ELISA assays using serum from proven systemic candidiasis patients and controls. Our immunoblotting results demonstrate that the recombinant Sap2 protein was recognized as a single band of approximately 41 kDa by systemic candidiasis patient serum samples and no cross reactivity was observed in healthy controls. On evaluating the diagnostic potential of the rSap2 antigen using an ELISA-based approach, our results show that anti-Sap2 Ig, IgG and IgM antibodies could be detected in the sera of proven candidiasis patients. Of note, the differences in Sap2 antibody titers observed amongst patients and controls were similar to the serological response observed when heat-killed whole-cell Candida was used as a coating antigen.ConclusionIn summary, the rSap2 protein from C. parapsilosis has the potential to be used in the diagnosis of systemic candidiasis, providing a rapid, convenient, accurate, and cost-effective strategy. Our results indicate that the rSap2 protein from C. parapsilosis can be used to detect and diagnose systemic candidiasis infection in human patients and can be used as an alternative/replacement of whole-cell Candida-based ELISA procedures, which are currently in use.

Methylation of the 4q35 D4Z4 repeat defines disease status in facioscapulohumeral muscular dystrophy.

Genetic diagnosis of facioscapulohumeral muscular dystrophy (FSHD) remains a challenge in clinical practice as it cannot be detected by standard sequencing methods despite being the third most common muscular dystrophy. The conventional diagnostic strategy addresses the known genetic parameters of FSHD: the required presence of a permissive haplotype, a size reduction of the D4Z4 repeat of chromosome 4q35 (defining FSHD1) or a pathogenic variant in an epigenetic suppressor gene (consistent with FSHD2). Incomplete penetrance and epistatic effects of the underlying genetic parameters as well as epigenetic parameters (D4Z4 methylation) pose challenges to diagnostic accuracy and hinder prediction of clinical severity. In order to circumvent the known limitations of conventional diagnostics and to complement genetic parameters with epigenetic ones, we developed and validated a multistage diagnostic workflow that consists of a haplotype analysis and a high-throughput methylation profile analysis (FSHD-MPA). FSHD-MPA determines the average global methylation level of the D4Z4 repeat array as well as the regional methylation of the most distal repeat unit by combining bisulphite conversion with next-generation sequencing and a bioinformatics pipeline and uses these as diagnostic parameters. We applied the diagnostic workflow to a cohort of 148 patients and compared the epigenetic parameters based on FSHD-MPA to genetic parameters of conventional genetic testing. In addition, we studied the correlation of repeat length and methylation level within the most distal repeat unit with age-corrected clinical severity and age at disease onset in FSHD patients. The results of our study show that FSHD-MPA is a powerful tool to accurately determine the epigenetic parameters of FSHD, allowing discrimination between FSHD patients and healthy individuals, while simultaneously distinguishing FSHD1 and FSHD2. The strong correlation between methylation level and clinical severity indicates that the methylation level determined by FSHD-MPA accounts for differences in disease severity among individuals with similar genetic parameters. Thus, our findings further confirm that epigenetic parameters rather than genetic parameters represent FSHD disease status and may serve as a valuable biomarker for disease status.

Special Issue on the Development of Microfluidic Devices for Medical Applications

Microfluidics refers to the science of handling fluids in microstructures and has been widely used in the medical field to miniaturize conventional drug delivery systems, bioassays, and diagnostics [...]

Evolution of Machine Learning in Tuberculosis Diagnosis: A Review of Deep Learning-Based Medical Applications

Tuberculosis (TB) is an infectious disease that has been a major menace to human health globally, causing millions of deaths yearly. Well-timed diagnosis and treatment are an arch to full recovery of the patient. Computer-aided diagnosis (CAD) has been a hopeful choice for TB diagnosis. Many CAD approaches using machine learning have been applied for TB diagnosis, specific to the artificial intelligence (AI) domain, which has led to the resurgence of AI in the medical field. Deep learning (DL), a major branch of AI, provides bigger room for diagnosing deadly TB disease. This review is focused on the limitations of conventional TB diagnostics and a broad description of various machine learning algorithms and their applications in TB diagnosis. Furthermore, various deep learning methods integrated with other systems such as neuro-fuzzy logic, genetic algorithm, and artificial immune systems are discussed. Finally, multiple state-of-the-art tools such as CAD4TB, Lunit INSIGHT, qXR, and InferRead DR Chest are summarized to view AI-assisted future aspects in TB diagnosis.

Cost-effectiveness of the implementation of [68Ga]Ga-PSMA-11 PET/CT at initial prostate cancer staging

BackgroundDespite its high specificity, PSMA PET/CT has a moderate to low sensitivity of 40–50% for pelvic lymph node detection, implicating that a negative PSMA PET/CT cannot rule out lymph node metastases. This study investigates a strategy of implementing PSMA PET/CT for initial prostate cancer staging and treatment planning compared to conventional diagnostics. In this PSMA PET/CT strategy, a bilateral extended pelvic lymph node dissection (ePLND) is only performed in case of a negative PSMA PET/CT; in case of a positive scan treatment planning is solely based on PSMA PET/CT results.MethodA decision table and lifetime state transition model were created. Quality-adjusted life years and health care costs were modelled over lifetime.ResultsThe PSMA PET/CT strategy of treatment planning based on initial staging with [68Ga]Ga-PSMA-11 PET/CT results in cost-savings of €674 and a small loss in quality of life (QoL), 0.011 QALY per patient. The positive effect of [68Ga]Ga-PSMA-11 PET/CT was caused by abandoning both an ePLND and unnecessary treatment in iM1 patients, saving costs and resulting in higher QoL. The negative effect was caused by lower QoL and high costs in the false palliative state, due to pN1lim patients (≤ 4 pelvic lymph node metastases) being falsely diagnosed as iN1ext (> 4 pelvic lymph node metastases). These patients received subsequently palliative treatment instead of potentially curative therapy.ConclusionInitial staging and treatment planning based on [68Ga]Ga-PSMA-11 PET/CT saves cost but results in small QALY loss due to the rate of false positive findings.

Non-invasive diagnostics of pathogenic bacteria using a breath sampler in children with cystic fibrosis

Cystic fibrosis (CF) is a common autosomal recessive disease causing thick, viscous secretions leading to pulmonary infections with pathogenic bacteria. As part of routine patient care, colonization and infection with these bacteria is monitored with cough swab or sputum cultures and sometimes bronchoalveolar lavage. In this cross-sectional proof-of-concept study in a cohort of CF patients we collected swabs or sputa and exhaled breath samples with the modular breath sampler (MBS), a newly developed two-way non-rebreathing sampling device. Pathogen specific polymerase chain reactions (PCRs) were performed on the MBS samples and compared with the results obtained with conventional diagnostics (i.e. culturing of swabs and sputa). A control group of stable asthma patients was used as negative control for the MBS measurements. The pathogens detected using MBS and conventional culturing differed: S. aureus was found more often in swab or sputum samples whereas Pseudomonas aeruginosa and S. pneumoniae were found more often in MBS samples. We hypothesize that this is due to sampling of different compartments, MBS samples are derived from the lower respiratory tract while cultures from cough swabs and sputa are dominated by pathogens residing in the upper respiratory tract. Another important difference is the readout, i.e. culture versus PCR. The majority of CF patients in whom P. aeruginosa was found did not have recent positive cultures suggesting higher sensitivity of MBS-based than conventional diagnostics. The majority of parents/patients found the MBS easy to use and less of a burden than respiratory sampling.

ЛУЧЕВАЯ И РАДИОНУКЛИДНАЯ ВИЗУАЛИЗАЦИЯ В ДИАГНОСТИКЕ АКТГ-ПРОДУЦИРУЮЩИХ НЕЙРОЭНДОКРИННЫХ ОПУХОЛЕЙ

Ectopic ACTH syndrome caused by excessive production of adrenocorticotropic hormone (ACTH) by a neuroendocrine tumor (NET) is an extremely rare disease, the main manifestation of which is pronounced hypercortisolism. In order to avoid the development of life-threatening complications and disability of the patient, timely topical diagnosis and rapid decision-making on further management tactics are necessary. The problem of the diagnosis of NET and differential diagnosis with other formations remains relevant and one of the little-studied. Despite the existing wide arsenal of methods of conventional diagnostics, functional and receptor imaging, the source of the disease remains unidentified in about 20% of patients. This article discusses the modern possibilities of NET visualization using conventional and radionuclide imaging methods, demonstrates the diagnostic capabilities of somatostatin-receptor scintigraphy and single-photon emission computed tomography combined with computed tomography (SPECT/CT) and combined positron emission and computed tomography (PET/CT) in the visualization of NET producing ACTH, and analyzes existing radiopharmaceuticals.

Four-Line C2*/CH* Optical Sensor for Chemiluminescence Based Imaging of Flame Stoichiometry

In the present work, an optical sensor was developed and calibrated for the purpose of non-intrusive equivalence ratio measurements in combustion systems. The sensor incorporates a unique four-line, single-sensor chemiluminescence imaging-based approach, which relies on the ratio of C2* and CH* radical-species intensities to obtain measurements of equivalence ratios. The advantage of the four-line sensor is the use of additional filtering to mitigate broadband luminescence signals, and its improvements over conventional two-line chemiluminescence diagnostics are discussed. The sensor was calibrated using a premixed bluff-body jet burner with a propane–air flame operating over a wide range of equivalence ratios. The results showed that the four-line processing technique improved the signal-to-noise ratio of the chemiluminescence images for all test cases. Calibrations of C2*/CH* intensity ratio to equivalence ratio were developed for both the four-line and two-line techniques. The calibrations were then used to create maps of local equivalence ratios in the flame-holding region. The maps revealed a non-uniform field of equivalence ratios due to the nature of the radical-species intensity profiles within the flame. Therefore, special consideration is required for calibration in order to accurately quantify equivalence ratios and apply these to diffusion flames.

Emerging Biosensors for Oral Cancer Detection and Diagnosis-A Review Unravelling Their Role in Past and Present Advancements in the Field of Early Diagnosis.

Oral cancer is a serious concern to people all over the world because of its high mortality rate and metastatic spread to other areas of the body. Despite recent advancements in biomedical research, OC detection at an early stage remains a challenge and is complex and inaccurate with conventional diagnostics procedures. It is critical to study innovative approaches that can enable a faster, easier, non-invasive, and more precise diagnosis of OC in order to increase the survival rate of patients. In this paper, we conducted a review on how biosensors might be an excellent tool for detecting OC. This review covers the strategies that use different biosensors to target various types of biomarkers and focuses on biosensors that function at the molecular level viz. DNA biosensors, RNA biosensors, and protein biosensors. In addition, we reviewed non-invasive electrochemical methods, optical methods, and nano biosensors to analyze the OC biomarkers present in body fluids such as saliva and serum. As a result, this review sheds light on the development of ground-breaking biosensors for the early detection and diagnosis of OC.

Possibilities of Conventional PD Measurements with Non-Sinusoidal Waveforms for Electric Vehicles

Electrical traction machines in electric vehicles are normally fed by converters with DC link voltages up to 800 V. The resulting voltage pulses place particular stress on the insulating system of the drivetrain. In order to be able to investigate insulating material samples, e.g. twisted pair enameled wire, with voltages of different shapes and high frequency, a shielded experimentalsetup for the investigation of partial discharges (PD) at low voltages and high frequencies is presented. A medium frequency transformer with a frequency range up to 2500 Hz is used for this purpose, fed by a linear power amplifier on the primary side. The amplifier has a slew rate of 52 V/μs and is capable of sourcing various voltage waveforms such as sinusiodal, triangularor rectangular, with a maximum frequency of 30 kHz. Electrical PD measuring methods according to IEC 60270 as well as acoustic and optical measurement methods are applied for PD diagnosis. The experimental setup is intended to demonstrate the possibilities and limitations of conventional PD diagnostics for nonsinusoidal voltages. Focus is placed on the application of filters, the damping behavior of the step-up transformer and the rise times of the voltages.

Conventional ultrasound diagnostics in dermatology

The imaging of changes to the skin, the subcutis and especially the regional lymph nodes by high-resolution ultrasound is an integral part of routine dermatological diagnostics. This is mainly done with electronic scanners operating at frequencies between 7.5 and 20 MHz (conventional ultrasound diagnostics). In addition, there are very high-frequency ultrasound systems (frequencies up to 100 MHz) that are used for special scientific questions. Ultrasound diagnostics has anumber of advantages over other cross-sectional imaging techniques but is more dependent than these on the individual experience of the examiner. Structured training and continuing education are therefore essential for ultrasound diagnostics, also in dermatology. The following overview describes the most important indications for conventional sonography in dermatology in addition to the physical, technical and administrative principles.

Tissue sampling is non-inferior in comparison to sonication in orthopedic revision surgery.

The aim of this study was to assess the role of sonication fluid cultures in detecting musculoskeletal infections in orthopedic revision surgery in patients suspected of having peri-prosthetic joint infection (PJI), fracture-related infections (FRI), or postoperative spinal implant infections (PSII). Between 2016 and 2019, 149 cases with a data set including sonication fluid cultures and tissue specimen and histological analysis were included. Accuracy of each diagnostic tool as well as the influence of antibiotic therapy was analyzed. Pathogens identified in the sonication cultures and in the associated tissue samples were compared based on the matching ofthe antibiograms. Therapeutic benefits were then assessed. Of 149 cases, 43.6% (n = 65) were identified as PJI, 2.7% (n = 4) as FRI, 12.8% (n = 19) as PSII, 6.7% (n = 10) as aseptic non-union, and 34.2% (n = 51) as aseptic implant loosening. The sensitivity and specificity of tissue and synovial specimens showed no significant difference with respect to sonication fluid cultures (sensitivity/specificity: tissue: 68.2%/96.7%; sonication fluid cultures: 60.2%/98.4%). The administration of antibiotics over 14days prior to microbiological sampling (n = 40) resulted in a lower sensitivity of 42.9% each. Histological analysis showed a sensitivity 86.3% and specificity of 97.4%. In 83.9% (n = 125) of the cases, the results of sonication fluid cultures and tissue specimens were identical. Different microorganisms were found in only four cases. In 17 cases, tissue samples (n = 5) or sonication (n = 12) were false-negatives. Sonication fluid culture showed no additional benefit compared to conventional microbiological diagnostics of tissue and synovial fluid cultures. Preoperative administration of antibiotics had a clearly negative effect on microbiologic test accuracy. In over 83.9% of the cases, sonication fluid and tissue cultures showed identical results. In the other cases, sonication fluid culture did not further contribute to the therapy decision, whereas other factors, such as fistulas, cell counts, or histological analysis, were decisive in determining therapy.

Distribution of Common and Rare Genetic Markers of Second-Line-Injectable-Drug Resistance in Mycobacterium tuberculosis Revealed by a Genome-Wide Association Study.

Point mutations in the rrs gene and the eis promoter are known to confer resistance to the second-line injectable drugs (SLIDs) amikacin (AMK), capreomycin (CAP), and kanamycin (KAN). While mutations in these canonical genes confer the majority of SLID resistance, alternative mechanisms of resistance are not uncommon and threaten effective treatment decisions when using conventional molecular diagnostics. In total, 1,184 clinical Mycobacterium tuberculosis isolates from 7 countries were studied for genomic markers associated with phenotypic resistance. The markers rrs:A1401G and rrs:G1484T were associated with resistance to all three SLIDs, and three known markers in the eis promoter (eis:G-10A, eis:C-12T, and eis:C-14T) were similarly associated with kanamycin resistance (KAN-R). Among 325, 324, and 270 AMK-R, CAP-R, and KAN-R isolates, 274 (84.3%), 250 (77.2%), and 249 (92.3%) harbored canonical mutations, respectively. Thirteen isolates harbored more than one canonical mutation. Canonical mutations did not account for 103 of the phenotypically resistant isolates. A genome-wide association study identified three genes and promoters with mutations that, on aggregate, were associated with unexplained resistance to at least one SLID. Our analysis associated whiB7 5'-untranslated-region mutations with KAN resistance, supporting clinical relevance for this previously demonstrated mechanism of KAN resistance. We also provide evidence for the novel association of CAP resistance with the promoter of the Rv2680-Rv2681 operon, which encodes an exoribonuclease that may influence the binding of CAP to the ribosome. Aggregating mutations by gene can provide additional insight and therefore is recommended for identifying rare mechanisms of resistance when individual mutations carry insufficient statistical power.

Terahertz biophotonics poised to provide an alternative to conventional medical diagnostics

Biomedical applications harness the effectiveness of promising wave technology.

Doppler Ultrasonography Derived Maximal Systolic Acceleration: Value Determination With Artificially Induced Stenosis.

BackgroundIn diagnosing peripheral arterial disease (PAD), medial arterial calcification (MAC) hampers arterial compression and could lead to unreliable ankle brachial index (ABI), toe brachial index (TBI) and toe pressure (TP). Doppler ultrasonography (DUS) derived maximal systolic acceleration (ACCmax) might be more accurate to diagnose PAD. In an in vitro study, a strong correlation between ACCmax and the severity of stenotic disease was determined. The aim of this study was to investigate the ACCmax in correlation with conventional non-invasive diagnostics in an in vivo setting. Methods: In twelve healthy individuals, an arterial stenosis was mimicked by compression on the common femoral artery by an ultrasounds probe, creating a local stenosis of 50%, 70% and 90%. The ABI, TBI, TP and several DUS parameters (including ACCmax) were assessed at the ankle during these different degrees of stenosis. All DUS parameters were measured separately by two observers to determine the interobserver variability. Results: Overall the ABI, TBI, TP, ACCmax, ACCsys and PSV decreased significantly when the degree of stenosis increased. The ACCmax showed the highest correlation with the degree of stenosis (r −.884), compared to ABI (r −.726), TBI (r −.716) and TP (r −.758). Furthermore, the interobserver variability of ACCmax was excellent, with an intraclass correlation coefficient (ICC) of .97. Conclusion: ACCmax is an accurate non-invasive DUS parameter to diagnose and assess the severity of a mimicked arterial stenosis in healthy individuals. Further prospective assessment of the clinical value of ACCmax and its potential benefits in patients with PAD is needed.

Conventional and non-conventional diagnostics of a stable atmospheric pressure DC normal glow microplasma discharge intended for in situ TEM studies

A simple setup utilizing parallel flat electrodes with a 50–150 μm interelectrode distance divided by a Kapton spacer with a 1 mm diameter whole as discharge region intended for in situ transmission electron microscope studies is presented. The rather small setup operated in Ar or He results in an atmospheric pressure DC normal glow discharge and is investigated using various diagnostics. I–V characteristics show a glow-like behavior of the microplasma. Significant differences due to the working gas, electrode material and electrode distance have been observed. Currents in the range of 0.5–3 mA resulted in electrode potentials of 140–190 V for most experimental conditions. Optical emission spectroscopy and imaging revealed stable plasma operation and enabled the determination of current densities (approx. 16 mA mm−2 for He, or 28 mA mm−2 for Ar) independent of the input current as the discharge channel grows in diameter. Sheath thicknesses in the range of a few μm have been calculated by the collision-dominated Child–Langmuir law and trends are confirmed by the optical imaging. Energy flux measurements revealed a pronounced effect of ions on the measurement process and resulted in high energy fluxes locally up to 275 W cm−2. Effective secondary electron emission coefficients ranging from 1 to 1.6 depending on the discharge conditions have been determined based on the energy balance at the cathode.

Histopathological evaluation of nonalcoholic fatty liver disease : Automated evaluation of liver biopsies

Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent chronic liver diseases with arising incidence in industrial countries. This is accompanied by an increased prevalence for NAFLD-associated liver cirrhosis and an increased risk for developing hepatocellular carcinoma. The current gold standard in the diagnostics is a liver biopsy. The histopathological evaluation is performed through semiquantitative scoring. To optimize the standardization and quantification of the existing scoring systems, in the coming years procedures with artificial intelligence, such as deep learning models could be used. Fields of application could be the supplementation of conventional histopathological diagnostics, the identification of new predictive parameters for estimating the prognosis and the prediction of a possible response to treatment.

Abstract P3-02-11: Towards a new standard for staging: A comparative study of [18F]FES PET/CT vs [18F]FDG PET/CT in patients with clinical stage II/III and locoregional recurrent estrogen receptor positive breast cancer

Abstract Introduction: Accurate staging of patients with locally advanced breast cancer or locoregional recurrent (LRR) breast cancer is essential for providing a tailored treatment. According to current guidelines, staging is preferably done with positron emission tomography (PET) using 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), combined with diagnostic computed tomography (CT). Previous studies suggest that [18F]FDG PET might underperform in patients with grade 1-2, estrogen receptor positive (ER+) breast cancer as these tumors are often metabolically less active than other subtypes of breast cancer. Thus, there is a need to improve current diagnostics for this population. 16α-[18F]-fluoro-17β-estradiol ([18F]FES), radioactive labeled estradiol, has emerged as a powerful imaging tool for in vivo visualization of ER+ lesions. The aim of this study was to investigate whether [18F]FES PET/CT improves staging of patients with clinical stage II/III or LRR ER+ breast cancer, compared to [18F]FDG PET/CT. Methods: Patients with clinical stage II/III or LRR 1-2, ER+ breast cancer were included in this prospective multicenter clinical trial (NCT03726931). All patients underwent a [18F]FES PET/CT and a [18F]FDG PET/CT scan. Both PET scans were visually assessed, independently of each other. Visually suspect lesions for malignancy were verified pathologically (by biopsy or fine needle aspiration) or by conventional imaging (mammography, ultrasound, magnetic resonance imaging, CT). The stage of the disease was determined twice in a multidisciplinary team, based on conventional diagnostics (conventional imaging and pathology) and [18F]FDG PET/CT or [18F]FES PET/CT, respectively. Semi-quantitative PET parameters, standardized uptake values (SUVs) and tumor-to-blood ratios (TBRs), were obtained by defining volumes of interest in the aorta ascendens and in suspect tumor lesions. These PET parameters were correlated with various pathological features, such as histological subtype, grade and ER, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression. Results: A total of 40 patients were included. On patient level, the sensitivity of [18F]FES PET/CT and [18F]FDG PET/CT to detect ER+ disease was 87.5% and 82.5%, respectively. [18F]FES PET/CT correctly determined the stage in 34/40 patients (85.0%) whereas [18F]FDG PET/CT correctly determined the stage in 29/40 patients (72.5%). [18F]FES PET/CT correctly changed the stage in 8/40 patients (20.0%) with upstaging in 6 patients and downstaging in 2 patients, compared to [18F]FDG PET/CT. On lesion level, a total of 140 suspect lesions were analyzed: 82 lesions were pathologically verified whereas 58 were radiographically verified. The sensitivity for lesion detection on [18F]FES PET/CT and [18F]FDG PET/CT was 90.6% and 77.3%, respectively. [18F]FES PET/CT identified more lesions correctly: 120/140 (85.7%) lesions vs 103/140 (73.6%) on [18F]FES PET/CT vs [18F]FDG PET/CT, respectively. [18F]FES PET/CT also missed less lesions (12/140, 8.6%) compared to [18F]FDG PET/CT (29/140, 20.7%). [18F]FES SUVmax, SUVmean, SUVpeak and TBR correlated with ductal subtype and percentage of PR expression (p <0.05, positive correlation). Conclusion: [18F]FES PET/CT improves disease staging in patients with stage II/III and LRR grade 1-2, ER+ breast cancer, compared to [18F]FDG PET/CT. This is in line with the ability of the tracer to identify malignant lesions more accurately in this patient population and supports further development of [18F]FES for staging grade 1-2, ER+ breast cancer. Citation Format: Ramsha Iqbal, Emma C Bonjer, Annette van Zweeden, Lemonitsa H Mammatas, Jaap JM Teunissen, Jan Booij, Gwen MP Diepenhorst, Laura Schijf, Susanne van der Velde, Katya Duvivier, Ellis Barbé, Daniela E Oprea-Lager, Catharina W Menke-van der Houven van Oordt. Towards a new standard for staging: A comparative study of [18F]FES PET/CT vs [18F]FDG PET/CT in patients with clinical stage II/III and locoregional recurrent estrogen receptor positive breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-02-11.

Microfluidics for Cancer Biomarker Discovery, Research, and Clinical Application.

Currently, cancer is the leading cause of death and its incidence and mortality is growing rapidly all over the world. One of the confounding factors contributing to the failure of conventional cancer diagnostics and treatment strategies is a high degree of intratumoral and intertumoral heterogeneity at the single-cell and molecular levels. Recent innovations in microfluidic techniques have revolutionized single-cell and single-molecule research and challenged the conventional definition of a "biomarker." Alongside classic cancer biomarkers such as circulating tumor DNA or circulating tumor cells (CTC), tumor cell heterogeneity, transcriptional and epigenetic cell states and their abundance in the tumor microenvironment have been demonstrated to impact disease progression and treatment response. Utilizing high-throughput, robust microfluidic techniques for the detection, isolation, and analysis of various cancer biomarkers, valuable information about the tumor can be obtained for clinical decision-making. This chapter presents clinically relevant advances of cancer biomarker research using microfluidics technology and identifies the emerging applications for disease diagnosis, monitoring, and personalized treatment.

Conventional and molecular diagnostics for detection of causative fungi in clinical samples of human dermatomycosis

Conventional and molecular diagnostics for detection of causative fungi in clinical samples of human dermatomycosis