In-house Test Research Articles

ADAMTS13 Overtesting in Hospitalized Patients with Suspected TTP: A Retrospective Study

Introduction: Acquired thrombotic thrombocytopenic purpura (aTTP) is a life-threatening disease characterized by thrombotic microangiopathy with an untreated mortality rate of >90%. Diagnosis relies on ADAMTS13 testing, in-house testing is reported to cost $4732/test. Average cost of treating typical aTTP episode with caplacizumab is $270,000. Validated scoring systems like PLASMIC/French-TMA models in conjunction with clinical evaluation may help with early diagnosis and avoid unnecessary testing. Methods: We identified 68 unique hospitalized adult patients with no history of TTP who had ADAMTS13 activity checked between 12/2019 and 04/2022. Collected data included demographics, COVID status, location where test was ordered, test results, time for test to return, whether peripheral smears were ordered, evidence of PLASMIC score documentation and final diagnosis. Descriptive statistics were utilized to report data as means and percentages. Results: Median age was 52±17 years with an equal distribution of males (34/68, 50%) and females (34/68, 50%). 54/64 (84.4%) patients had a COVID negative status. 35/68 (51.5%) tests were ordered in the intensive care unit and the remaining 33/68 (48.5%) tests were ordered on regular floor patients. 65/68 (95.6%) ADAMTS13 tests returned negative. Mean time for ADAMTS13 to return was 2.67±1.51 days. While 52/68 (76.5%) had a peripheral smear ordered, 51/68 (75%) had no documentation of PLASMIC score. Retrospectively calculated PLASMIC scores revealed 31 (45.6%) with low-risk, 22 (32.3%) with intermediate-risk and 15 (22.1%) with high-risk. Only 5/68 (7.4%) were ultimately diagnosed with TTP and 15/68 (22%) in the non-TTP category were treated with PLEX and/or steroids before results were available. DIC, Sepsis, COVID, alcohol toxicity/cirrhosis and ITP were final diagnoses in 40/68 (58.8%) patients (Table 1). Conclusions: There is a pattern of ADAMTS13 overtesting in the hospitalized setting. PLASMIC and French-TMA scoring models offer high sensitivity/specificity and should be used to enhance clinical judgement and guide initial management. A high index of suspicion, physician education about expensive tests, EMR pop-ups as deterrents can help with risk stratification to curb unnecessary testing. In-house ADAMTS13 testing offers rapid results and thus reduce plasma utilization as our study revealed 15/68 (22%) non-TTP patients were treated for TTP before results arrived. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

State of the art on challenges for friction material manufacturers – raw materials, regulations, environmental, and NVH aspects

Friction materials have played a crucial role in safe movement of automobiles and in protection of human life. Enormous cost has incurred in validation of new developed brake pad, a critical safety component, as it involves a lot of inhouse testing along with field testing in different terrains. Further, with an unexpected pandemic and wars, creeping raw material price increases which is a major issue even though researchers have tried to develop innovative materials, which can perform multitasks. Moreover, a paradigm shift towards hybrid and electric vehicles required adjustments in design strategies, related to new friction materials for brakes. The regenerative braking mechanism has taken a major role in electric vehicles (EVs). Therefore, the friction pad is rarely used, which leads to rust/corrosion issues. In addition, the exhaust particles now pale in comparison to non-exhaust emissions. It is a newly identified challenge faced by friction industry as the brake pad wear is one of main contributors of non-exhaust emissions. Also, with no engine noise to cover, the silent nature of EVs creates noise and vibration issues in brake pad even more apparent. Hence, this paper has focused critically on challenges for friction material manufacturers in terms of regulations and raw materials followed by environmental issues and shift towards EVs and NVH requirement. Further, it has discussed with some possible suggestions to reduce the same.

Lead equivalence testing using a custom-built testing kit.

Radiation protective garments should undergo a quality assurance regime comprising of an acceptance test of the lead equivalence before the garment is introduced into clinical service, followed by routine periodic visual and fluoroscopic inspections throughout its remaining clinical lifespan. The IEC 61331-1:2014 [1] is the leading standard outlining the methodology for testing of lead equivalence of these garments and forms the basis of the Australian/New Zealand Standards(1999) [2]. This study outlines the design and development of an IEC compliant broad beam lead equivalence testing setup, using an in-house custom-built testing kit (CBTK). The practicality and robustness of this kit was performance tested using lead equivalence measurements on 97% pure lead sheets. Hospital radiation protective garments are predominantly made of lead-free or lead-composite materials due to their light weight, as such, a set of lead-free (N-Pb) samples was also performance tested. These samples were tested using two different beam qualities; a total filtration of 2.5 mmAl and 0.25 mmCu added filtration, both at 102 kVp. Samples with thicknesses of 0.25mm, 0.35mm and 0.50mm were used. The differential between labelled and measured lead equivalence averaged 3% for both the 'pure-lead' samples and N-Pb samples, with uncertainty of less than 7%. At 102 kVp, the use of Cu or Al filtration has marginal effect on measured lead equivalence for pure lead or N-Pb samples. The efficacy of utilizing the CBTK with a solid-state detector for lead equivalence testing was demonstrated through its ease of use, consistency and precision.

Wear Behaviour of Multilayer Al-PVD-Coated Polymer Gears.

A comprehensive experimental investigation of the wear behaviour of coated spur polymer gears made of POM is performed in this study. Three different thicknesses of aluminium (Al) coatings were investigated and deposited by the Physical Vapour Deposition (PVD) process. The Al coating was deposited in three steps: By plasma activation, metallisation of the aluminium by the magnetron sputtering process, and plasma polymerisation. The wear of the gears was tested on an in-house developed testing rig for different torques (16, 20, and 24 Nm) and a rotational speed of 1000 rpm. The duration of the experiments was set to 13 h, when the tooth thickness and, consequently, the wear of the tooth flank were recorded. The experimental results showed that the influence of metallisation with aluminium surface coatings on the wear behaviour of the analysed polymer gear is not significantly important. The results also showed that the gears with a thicker aluminium coating showed greater wear than gears with a thinner coating or even without a coating. This is probably due to the fact that the aluminium particles that started to deviate during gear operation represented the abrasive material, which led to the faster wear of the contacting surfaces of the meshing gear flanks.

Liquid Phase Identification in Wet Steam Transonic Flows by Means of Measurement Methods

The major goal of this study is comparing the results of heterogeneous and homogeneous condensation through a CD nozzle. The experimental technique for liquid phase assessment in wet steam transonic flow is tested under real conditions in an in-house steam tunnel test rig. The flow was modelled numerically using an in-house CFD code for performing the heterogeneous and homogeneous condensation models. For the comparison between CFD results and experimental data, the static pressure distribution throughout the nozzle bottom wall were chosen. One may observe a good agreement of the CFD results with experimental data. The presented approach can be used in the future for searching the reasons for the lack of accuracy between experimental and numerical static pressure distribution in the condensing steam flows.

Analysis of the moist air transonic flow in the symmetric and asymmetric nozzle of the low expansion

Condensation has a negative impact on turbomachinery efficiency in many energy processes. This paper compares the expansion of moist air in symmetric and asymmetric nozzles with a low expansion rate. The presented numerical study is supported by analytical and experimental research. The experimental tWesting was carried out using an in-house experimental test rig where two nozzles were examined for moist air with relative humidity of about 25%. The nozzles were tested for a supersonic outlet, as well as for the outlet condition with elevated pressure, which resulted in the occurrence of a normal shock in the test section. The asymmetric nozzle profile is congruent with the symmetric nozzle. However, the nozzle walls are shifted linearly in the flow direction. The Schlieren photography technique and static pressure measurements on the nozzle wall were used for qualitative identification of both condensation and shock waves. The presented numerical modelling was conducted using commercial computational fluid dynamics software extended with an in-house condensation model. The code was validated against in-house experiment as well as against the data available in the literature. The analysis of the flow in the considered two types of nozzles with a very low expansion rate revealed very interesting structures of pressure waves. The impact of the linear shift of the nozzle walls on the condensation process and the interaction of the condensation wave with aerodynamic oblique as well as normal shock waves were investigated.

A comprehensive analysis of the moist air transonic flow in a nozzle with a very low expansion rate

• Experimental study of the moist air transonic flow in a nozzle with a low expansion rate. • Mathematical models of homogeneous condensation. • The study of the effect of air relative humidity on the expansion process. • The study of the interaction between condensation and pressure waves. Inevitable and undesirable as it is, phase transition has a significant impact on the fluid flow efficiency in many energy processes. This paper deals with the impact of water vapour condensation and liquid water evaporation in the moist air expansion in a nozzle with a low expansion rate. The presented comprehensive analysis includes a numerical study supported by analytical and experimental research. The experimental study concerning measurements of atmospheric air transonic flows was carried out using an in-house experimental test rig. A nozzle with a low expansion rate of P ̇ ≈ 1000 s - 1 was investigated experimentally at different inlet air relative humidity values included in the range of 25 to 51 %. The nozzle was measured for supersonic outlet conditions, as well as with elevated back pressure (78 kPa). The technique of Schlieren photography and static pressure measurement on the nozzle wall were used for qualitative identification of both condensation and shock waves. The presented numerical modelling was conducted using commercial computational fluid dynamics software extended with an in-house condensation model. The code was validated against experimental data and data available in the literature. The analysis of the flow in the nozzle with a very low expansion rate revealed very interesting structures of pressure waves. The impact of relative air humidity on the condensation process and the interaction of the condensation wave with aerodynamic oblique as well as normal shock waves were investigated. It is observed that the higher the air relative humidity value, the more difficult it is to identify aerodynamically induced oblique shock waves in the flow. Finally, considering that the efficiency drop induced by the phase change can reach up to 10 %, the impact of condensation on the expansion process efficiency is presented.

Selection of an Appropriate In Vitro Susceptibility Test for Assessing Anti-Pythium insidiosum Activity of Potassium Iodide, Triamcinolone Acetonide, Dimethyl Sulfoxide, and Ethanol.

The orphan but highly virulent pathogen Pythium insidiosum causes pythiosis in humans and animals. Surgery is a primary treatment aiming to cure but trading off losing affected organs. Antimicrobial drugs show limited efficacy in treating pythiosis. Alternative drugs effective against the pathogen are needed. In-house drug susceptibility tests (i.e., broth dilution, disc diffusion, and radial growth assays) have been established, some of which adapted the standard protocols (i.e., CLSI M38-A2 and CLSI M51) designed for fungi. Hyphal plug, hyphal suspension, and zoospore are inocula commonly used in the drug susceptibility assessment for P. insidiosum. A side-by-side comparison demonstrated that each method had advantages and limitations. Minimum inhibitory and cidal concentrations of a drug varied depending on the selected method. Material availability, user experience, and organism and drug quantities determined which susceptibility assay should be used. We employed the hyphal plug and a combination of broth dilution and radial growth methods to screen and validate the anti-P. insidiosum activities of several previously reported chemicals, including potassium iodide, triamcinolone acetonide, dimethyl sulfoxide, and ethanol, in which data on their anti-P. insidiosum efficacy are limited. We tested each chemical against 29 genetically diverse isolates of P. insidiosum. These chemicals possessed direct antimicrobial effects on the growth of the pathogen in a dose- and time-dependent manner, suggesting their potential application in pythiosis treatment. Future attempts should focus on standardizing these drug susceptibility methods, such as determining susceptibility/resistant breakpoints, so healthcare workers can confidently interpret a result and select an effective drug against P. insidiosum.

Transient thermal measurement on nano-metallic sintered die-attach joints using a thermal test chip

The rapid development of power electronics has challenged the thermal integrity of semiconductor packaging. Further developments in this domain can be supported significantly by utilizing fast and flexible thermal characteristic evaluation. This study employs the transient dual interface method (TDIM) to characterize and compare the thermal resistance of Ag- and Cu-sintered die-attach joints using an in-house developed thermal test chip (TTC). The proposed TTC with 82.5% active area achieves a temperature sensitivity of 12 Ω/K and maximum power of 360 W per cell, which are 50% and 44% higher than the state-of-the-art, respectively. The uniformity of the temperature distribution (1 °C at 68 W) is verified by infrared thermography. The cost-effective manufacturing process allows the design to be applied to any substrate, such as SiC or GaN. Ag and Cu sintering is performed to bond the TTC on a Cu substrate, and the junction-to-case thermal resistance of the sintered structures is extracted. The lowest junction-to-case thermal resistance of 0.144 K/W is measured for the device sintered using Ag paste. Meanwhile, the Cu sintered structure exhibits a comparable value of 0.158 K/W. The proposed TTC in combination with TDIM accelerates the introduction of novel and cost-effective materials such as Cu.

Novel procedure for the identification of a starting point for the CMP

Abstract In the field of precision optics, more and more glass materials that are difficult to machine are being used because of their interesting optical properties. At the same time, the geometries are getting more demanding and the tolerances to be achieved are tighter. The establishment of an efficient process chain is therefore becoming an ever-greater challenge. Particularly in the field of CMP, knowledge of the machining properties of pads and slurries are required to design efficient processes. This knowledge has to be gained through time-consuming in-house tests, as the manufacturers of the consumables are usually only able to provide basic data. In addition, the boundary conditions under which the data were collected are often incomplete defined and thus not comparable. The novel methodical procedure presented here for the initial design of CMP processes is based on a standardized procedure for carrying out the tests. From the resulting database, a starting point for the design of own processes can be identified quickly and unerringly. This article describes the structure of the procedure as well as the necessary background. In addition, the visualization and the procedure for selecting start parameters are discussed using an example application.

Novel Family of High-Gain Nonisolated Multiport Converters With Bipolar Symmetric Outputs for DC Microgrids

Bipolar dc grid systems are fast gaining attraction for renewable energy source integration, because of their merits of higher reliability, efficiency, and robustness as compared to the unipolar dc grids. However, the progress in multiport converters, resulting into lower cost and more compact design for bipolar microgrid systems, is fairly slow. Therefore, this article proposes a novel family of five nonisolated multiport dc–dc converter topologies with bipolar symmetric outputs. The performance and key operational features of the proposed converters under varying input voltages, duty cycles and loads are numerically verified and experimentally on an in-house test setup to prove the concept of the proposed converters. In the experimental validation, the operation of the converter under simultaneous and arbitrary individual power transfer from two input ports is tested. Furthermore, the easy integration of the proposed converters with a multilevel inverter to achieve high-quality ac voltages is demonstrated. As compared to the few existing counterparts, the proposed converters have a competitive edge in terms of higher number of input ports and voltage gains. Alongside the possibility of arbitrary independent power flow from the input ports, inherently symmetrical outputs require a simple balance control for asymmetrical members of the family.

Icephobicity of aluminium samples is not affected by pH-generated surface charge

In this study, a comprehensive analysis of the pH-dependent contact angles, freezing temperatures and ice adhesion on aluminium samples is presented. It is not yet known whether externally applied electric fields or charged interfaces sufficiently affect the heterogeneous freezing and ice adhesion in order to provide technical solutions for refrigeration engineering, de-icing techniques and food preservation. It was found that surfaces charges that are generated on polished aluminium samples by changing the pH value of the adjacent KCl solution significantly reduce the advancing contact angle. The effect of surface charges on the freezing behaviour was determined by cooling an array of droplets of KCl solutions with pH values between 3 and 12 with a cooling rate of 1Kmin−1. Ice adhesion was evaluated using an in-house developed pusher test at -10°C in a climate chamber. Both icephobicity tests revealed that surface charges seem ineffective to significantly change the freezing behaviour and ice adhesion strength on polished aluminium samples.

Evaluation of "Real-Time" Fatal Drug Overdose Surveillance by King County Medical Examiner's Office, Seattle, Washington.

To address the challenges in monitoring the continuously accelerating drug overdose epidemic, the King County Medical Examiner's Office in Seattle, Washington, instituted a "real-time" fatal drug overdose surveillance project, depending on scene investigations, autopsy findings, and in-house testing of blood, urine, and drug evidence collected from death scenes. Validation of the project's rapid death certification methodology from 2019 through 2021 was performed at the following 3 levels: blood testing, urine testing, and death certification, and for the following 4 drugs: fentanyl, opiate, methamphetamine, and cocaine. For blood testing, sensitivity ranged from 90% to 99%, and specificity ranged from 86% to 97%. For urine testing, sensitivity ranged from 91% to 92%, and specificity ranged from 87% to 97%. The positive predictive value for cocaine was poor for both blood testing (57%) and urine testing (72%). Of 1034 deaths, 807 were certified as overdose by rapid methodology, and 803 (99.5%) were confirmed by formal toxicology results. Manners of death were changed from accident to natural in 3 of 1034 cases (0.29%). Results of this study indicate that the rapid overdose surveillance methodology described in this study offers benefits to families and provides useful, timely information for responding law enforcement and public health agencies.

P458 Comparison of PCR protocols for detecting Histoplasma capsulatum and Coccidioides spp. DNA through a multicenter study

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PMIntroductionIn-house real-time PCR (qPCR) is increasingly used for the diagnosis of endemic mycoses and diverse assays are in use in specialized laboratories. External quality control is currently lacking.ObjectiveTo compare the performance of different molecular detection protocols for the detection of Histoplasma capsulatum and Coccidioides spp. in a multicenter study involving five European laboratories.MethodsTwo test sample panels were sent to each laboratory which performed the analysis with their in-house assays. Recipients were blinded to sample content. The Histoplasma-panel included 14 samples representing a range of concentrations of Histoplasma DNA (n = 7), as well as a negative control and DNA from other fungi to test for specificity (Paracoccidioides lutzii n = 1; Blastomyces dermatitidis n = 1; Aspergillus fumigatus n = 1; Emergomyces spp. n = 2, and Candida albicans n = 1). The Coccidioides-panel included 10 samples representing a range of DNA concentrations of Coccidioides posadasii (n = 6), as well as a negative control and DNA from other fungi to test specificity (Uncinocarpus reesii n = 1; Trichophyton violaceum n = 1; and Candida albicans n = 1). Regarding techniques used, four laboratories used Histoplasma qPCRs, and one laboratory a conventional PCR and a broad-range PCR (brPCR) for fungal DNA. Four laboratories used different Coccidioides qPCRs and one laboratory a brPCR to detect Coccidioides DNA.ResultsConcerning the Histoplasma panel, qPCR assays were the most sensitives and agreement in the lowest detected amount of Histoplasma DNA was very suitable, ranging from 1 pg to 4 pg [<1 genomic equivalent (mean sensitivity: 96.4%)]. The lowest detected amount of Histoplasma DNA by cPCR (sensitivity 71.4%) and the brPCR (sensitivity 42.9%) was 0.1 and 10 pg, respectively. Overall, sensitivity ranged from 42.9-100% (mean 83.3%). Overall specificity ranged from 78.6%-100%, with false positive results occurring with high DNA concentrations (200 pg/μl) of Blastomyces spp. in two laboratories that used qPCR, Emergomyces spp. by qPCR in one laboratory and Aspergillus in one laboratory that used cPCR. Concerning the Coccidioides panel, sensitivity ranged from 33.3-100% (mean 76.6%), and agreement of the lowest detected amount of Coccidioides DNA by qPCR ranged from 1-16 pg (<1 genomic equivalent) (mean sensitivity: 87.5%) and in the brPCR 10 pg (sensitivity 33.3%). Specificity was between 87.5%-100%, with one false positive result occurring with high DNA concentrations (20 pg/μ) of Uncinocarpus in one laboratory using qPCR.ConclusionSpecific protocols based on qPCR showed better sensitivity than conventional and brPCR. These methods are useful for the rapid and sensitive detection Histoplasma and Coccidioides. Application of these tests on clinical samples may speed up diagnosis and potentially limit laboratory exposure to these fungi. Comparisons of in-house tests are essential to assess the performance and detect potential cross-reactivities and achieve a consensus.

A methodology to determine the thermal diffusivity of additively manufactured jet engine blades based on laser-induced temperature field

This paper presents a new methodology for the thermal diffusivity determination of additively manufactured jet engine blades by using active infrared thermography. The technique is combined with a dedicated procedure based on deep machine learning models. The investigated samples were fabricated from different metal alloy powders by using the Laser Engineered Net Shaping (LENS®) technique. The experimental data for model development were in the form of laser shot-induced temperature fields, obtained from an original, in-house developed test apparatus. The advantage of the proposed methodology is that it can be used for the non-destructive measurements of the additively manufactured jet engine blades, which distinguishes the presented approach from the traditional laser-flash technique or other well-established methods. The obtained experimental values of the thermal diffusivity are in good agreement with data measured using the ASTM standard test method. The presented non-destructive technique has significant implementation/commercialization potential when applied to quality control or diagnostic procedures of 3D-printed parts.

CFD Aided Ship Design and Helicopter Operation

In support of Canadian industrial and defence ship design and offshore helicopter operations, a series of Ship–Helicopter Operational Limits Analysis and Simulation (SHOLAS) projects are being conducted at the National Research Council Canada (NRC) in collaboration with Defence Research and Development Canada (DRDC). This study presents a brief overview of a Canadian in-house ship airwake simulation capability combining in-house high-fidelity wind-tunnel tests, full-scale sea trials, high-order computational fluid dynamics (CFD) tools, and realistic engineering-oriented flight simulators. This paper reports challenges and lessons learned during the course of the study, discusses the current capabilities and limitations of the CFD tools and the infrastructure required, and evaluates the gaps and barriers in industry adoption by focusing on how they could be overcome based on our current practice. After validating the CFD results of an updated version of a simplified frigate shape (SFS2) and the real-world Canadian Patrol Frigate (CPF), which are in reasonable agreement with the available in-house wind-tunnel and sea-trial data, the developed approach was recently applied to the design of an undisclosed Canadian ship. Among other applications, CFD airwake results were used with confidence as input to produce representative airwake features in industrial high-fidelity piloted flight simulators.

Cross-Reactivity of SARS-CoV-2 Nucleocapsid-Binding Antibodies and Its Implication for COVID-19 Serology Tests.

The emergence of the new coronavirus SARS-CoV-2 in late 2019 led to the global pandemic COVID-19, causing a profound socioeconomic crisis. Adequate diagnostic tools need to be developed to control the ongoing spread of infection. Virus-specific humoral immunity in COVID-19 patients and those vaccinated with specific vaccines has been characterized in numerous studies, mainly using Spike protein-based serology tests. However, Spike protein and specifically its receptor-binding domain (RBD) are mutation-prone, suggesting the reduced sensitivity of the validated serology tests in detecting antibodies raised to variants of concern (VOC). The viral nucleocapsid (N) protein is more conserved compared to Spike, but little is known about cross-reactivity of the N-specific antibodies between the ancestral B.1 virus and different VOCs. Here, we generated recombinant N phosphoproteins from different SARS-CoV-2 strains and analyzed the magnitude of N-specific antibodies in COVID-19 convalescent sera using an in-house N-based ELISA test system. We found a strong positive correlation in the magnitude of anti-N (B.1) antibodies and antibodies specific to various VOCs in COVID-19-recovered patients, suggesting that the N-binding antibodies are highly cross-reactive, and the most immunogenic epitopes within this protein are not under selective pressure. Overall, our study suggests that the RBD-based serology tests should be timely updated to reflect the constantly evolving nature of the SARS-CoV-2 Spike protein, whereas the validated N-based test systems can be used for the analysis of sera from COVID-19 patients regardless of the strain that caused the infection.

Development of an IoT integrated DMAIC model for process improvement in Indian SMEs: An empirical study

Lean Six Sigma (LSS) and the Internet of Things (IoT) facilitate an organisation to compete in the global market. The benefits of implementing the above-mentioned approaches were not realised by many Indian SMEs. The Indian SMEs contribute nearly about 30% of the country's GDP. Hence, this work focused on how Lean Six Sigma and the Internet of Things were deployed to improve the process performance in an Indian SME. IoT integrated LSS model was implemented to minimise lead time and enhance the quality of the product. Value Stream Mapping and line balancing techniques were used to minimise the lead time. To improve quality and service, an IoT-enabled in-house testing procedure was adopted and based on customer feedback, an android application was also developed to monitor the critical parameters at the customer end to enable preventive maintenance. An Augmented Reality based application was developed to simulate the sequence of the assembly process to facilitate training for the workers. To assess the benefits of implementation, a survey was conducted among people at various levels in the organization. This research resulted in a reduction of assembly lead time from 63.8 min to 24.4 min and an improvement in sigma level from 3.9 to 4.7. In the responses received from the survey, key issues faced during the implementation of the proposed model were identified. Key issues like resistance to change, poor interpersonal, lack of training, poor autonomy, timely decision making, and demand fluctuations during implementation are to be addressed for further effective implementation. The proposed model enhances the overall performance of the process in the manufacturing industry. Furthermore, it creates a driveway for Indian SMEs towards Industry 4.0.

EP04.01-008 Factors Impacting Time from Biopsy to Initiation of Treatment for Advanced NSCLC at an Academic Hospital and Affiliate Hospitals

Delays in initiation of treatment for advanced cancers are associated with poorer outcomes. In advanced NSCLC, one factor impacting time of treatment initiation is next-generation sequencing (NGS) testing. In our hospital system, Northwestern Medicine, the standard for NGS testing at Northwestern Memorial, the 894-bed academic hospital, is in-house reflex testing on all histologies and stages for a 50-gene panel of mutations and fusions. At affiliate hospitals, there is no set protocol so testing is sent to private vendors.

In-house testing for homologous recombination repair deficiency (HRD) testing in ovarian carcinoma: a feasibility study comparing AmoyDx HRD Focus panel with Myriad myChoiceCDx assay.

Homologous recombination repair (HRR) is the main mechanism of repair of DNA double-strand breaks. Its deficiency (HRD) is a common feature of epithelial ovarian cancers (EOCs). BRCA1/2 mutations and/or other aberrations in genes of HRR are well known causes of HRD and genomic instability. Poly ADP-ribose polymerase inhibitors (PARPi) have revolutionized the management of BRCA mutant EOCs and demonstrated activity in HRD tumor cells. Determining HRD status can provide informations on the magnitude of benefit for PARPi therapy. Myriad MyChoice CDx is a next generation sequencing- based in vitro diagnostic test that assesses the Genomic Instability Score (GIS) which is an algorithmic measurement of loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions using DNA isolated from formalin-fixed paraffin embedded tumor tissue specimens. However Myriad MyChoice CDx, is a centrally performed and costly assay, with no reimbursement scheduled, at least in Italy. In this report, we described our experience in performing the HRD Focus AmoyDx (Amoy Diagnostics Ltd, Xiamen, Fujian, China) on the same samples of EOCs evaluated with Myriad MyChoiceCDx assay. The overall percent agreement between AmoyDx and Myriad was 87.8% (65 of 74 tumors tested). All the 36 AmoyDx negative cases were confirmed to be negative by Myriad (negative predictive value, 100%). The concordance of the results with the gold standard Myriad MyChoice CDx assay suggest the feasibility and reliability of HRD testing in diagnostic laboratories with high-throughput NGS platforms and qualified personnel.