Surveillance Testing Research Articles

Identification and Classification of Skin Cancer Using a GUI and a Deep Neural Network

Abstract: Skin cancer, the most prevalent human malignancy1–3, is mainly detected directly, with initial surveillance, sonographic investigation, dissection, and pathological testing following. Due to the perfectly alright heterogeneity in their form, automated classification or skin conditions using imagery is tricky. Convolutional networks (CNNs) have shown promise in a variety of tasks with a large number of variables, such as item classification. 6–11. Using one CNN which was built side to side from photographs, we demonstrate how to identify lesion just by using pixels and illness labels as outputs. Early identification of skin cancers like melanoma and focal malignant tumors is critical for preventing disease development. Notwithstanding, there are a factors that affect detection capability. The use of medical image analysis in especially in the medical sectors has developed rapidly in recent years. . In this study, we used Convolutional Neural Networks (CNN) to diagnose and characterize cancer types given past clinical mri data. Some of our purpose of the study is developing CNN model to identify tumors by an efficacy of greater than 80%, limiting the untrue alarm rate in the predicted to less than 10%, attaining resolution of greater than 80%, and displaying raw details. As per computer findings, the proposed approach exceeds the additional choices undergoing investigation.

Case-control study to identify risk factors for SARS-CoV-2 infection among university students in the northeastern USA.

Curbing the coronavirus disease 2019 (COVID‐19) pandemic requires a thorough understanding of risk factors for transmission of SARS‐CoV‐2, the etiologic agent. Institutions of higher education present unique challenges for controlling disease spread because of features inherent to these settings. Our objective was to determine risk factors for SARS‐CoV‐2 infection among a university student population in the northeastern USA during the spring and fall 2021 semesters, using the case–control study design. Cases were defined as students with a newly diagnosed SARS‐CoV‐2 infection detected either through the robust PCR‐based surveillance testing program on campus or through healthcare testing if symptoms compatible with COVID‐19 were present. Controls were defined as students with negative SARS‐CoV‐2 status, based on consistently negative PCR results at the time of selection. A comprehensive questionnaire was administered to each student enrolled in the study, covering a broad range of campus life activities. A total of 446 cases and 1,185 controls were included in this study. Multivariable logistic regression analysis showed that recent party attendance (adjusted OR = 2.3, p < .0001), recently visiting a bar (aOR = 1.6, p = .007), living in a campus residence hall (aOR = 1.6, p = .001), fraternity/sorority membership (aOR = 1.8, p = .002), and recent travel (aOR = 1.3, p = .04) were associated with being a COVID‐19 case. Having an on‐campus job was negatively associated with being a COVID‐19 case (aOR = 0.6, p = .0003). Among cases, the most commonly reported symptoms were cough (43.9%), fatigue (38.1%) and sore throat (30.3%). These findings can be used to inform the development of COVID‐19 mitigation strategies and public health outreach efforts in university settings, thus reducing SARS‐CoV‐2 transmission among students and helping to preserve the vital education and research missions of these institutions.

Investigation and Mitigation of a Respiratory Syncytial Virus (RSV) Outbreak on an Adult Inpatient Leukemia Unit

<h3>Background</h3> In February 2020, an uptick in RSV infections was detected on an adult, inpatient leukemia unit at a tertiary oncology hospital. Upon outbreak identification, an epidemiological investigation was launched, and outbreak mitigation responses implemented. <h3>Methods</h3> All new RSV results were reviewed for connections to the uptick detected on the inpatient adult leukemia unit which houses patients on high-risk services. Upon identification of an outbreak, the Infection Control Department met with interdisciplinary stakeholders to implement a stepwise approach to stop the outbreak. The infection control team provided education to staff, implemented enhanced twice daily unit cleaning, performed daily unit rounds, monitored sick staff calls and performed daily patient chart reviews for symptoms. As additional cases were identified in roommates of index patients, further contact tracing and surveillance testing was performed. In response to continued detection of cases, all patients were placed on droplet precautions, the unit closed to new admissions, patients and healthcare staff were cohorted, employee surveillance testing was performed, and a physical containment barrier created. <h3>Results</h3> The Infection Control Department monitored outbreak activity and implemented mitigation responses between February 1, 2020, to March 24, 2020. There were 23 patient cases associated with this outbreak, 18 of which were hospital-acquired and 5 of which were community onset. 22 patients associated with the outbreak were on a high-risk service. There were 7 cases detected in healthcare workers. The outbreak was declared over when there were no cases within 2 incubation periods, 14 days. The unit subsequently returned to routine practices. <h3>Conclusions</h3> This outbreak investigation indicates that high-risk inpatient units require a multitude of interventions. Surveillance testing and quarantine are essential in this population, and mitigation efforts should be enacted as quickly as possible to stop transmission.

Abstract 689: A randomized phase III study assessing the efficacy of liquid biopsy in early diagnosis of recurrence and second malignancies in lung cancer survivors

Abstract We designed a 6,000-patient prospective, multi-institutional randomized clinical trial to assess the efficacy of liquid biopsy in early diagnosis of recurrence and second malignancies in lung cancer survivors. To ensure over 25% of participants are of disadvantaged or minority status, we have recruited multiple community hospitals (Jamaica, Flushing, Wyckoff, and Staten Island/Bronx satellites of Northwell hospitals) to the study in partnership with Memorial Sloan Kettering Cancer Center. Patients included in this study are survivors of non-metastatic non-small cell lung cancer, status-post definitive treatment (surgery or radiation) with no evidence of disease for at least one year. These patients may be on maintenance therapy for their prior lung cancer but may not have any other active malignancy at the time of enrollment. Participants will be randomized 1:1 to standard surveillance at the discretion of the treating physician or standard surveillance plus six-monthly methylation-based liquid biopsy tests over a two-year study period, and strict guidelines on follow-up of positive liquid biopsy testing will be provided to reduce harms from false positives or overdiagnosis. The primary endpoint of this study is the incidence of late stage cancer (distant recurrence or new primary cancer of stage III/IV). Secondary endpoints include incidence of early cancers (locoregional recurrence or new primary cancer of stage I/II), metastasis-free survival, and utilization of liquid biopsy versus standard of care scans. We will stratify our results by minority and socioeconomic status to specifically ascertain the effect of this intervention on populations of need. This is the first randomized controlled trial of liquid biopsy in a survivor population and the first trial utilizing liquid biopsy in a large minority population. We will have preliminary experiences to report in April 2022. Citation Format: Sana Raoof. A randomized phase III study assessing the efficacy of liquid biopsy in early diagnosis of recurrence and second malignancies in lung cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 689.

3D-Printed Dip Slides Miniaturize Bacterial Identification and Antibiotic Susceptibility Tests Allowing Direct Mastitis Sample Analysis.

The early detection of antimicrobial resistance remains an essential step in the selection and optimization of antibiotic treatments. Phenotypic antibiotic susceptibility testing including the measurement of minimum inhibitory concentration (MIC) remains critical for surveillance and diagnostic testing. Limitations to current testing methods include bulky labware and laborious methods. Furthermore, the requirement of a single strain of bacteria to be isolated from samples prior to antibiotic susceptibility testing delays results. The mixture of bacteria present in a sample may also have an altered resistance profile to the individual strains, and so measuring the susceptibility of the mixtures of organisms found in some samples may be desirable. To enable simultaneous MIC and bacterial species detection in a simple and rapid miniaturized format, a 3D-printed frame was designed for a multi-sample millifluidic dip-slide device that combines panels of identification culture media with a range of antibiotics (Ampicillin, Amoxicillin, Amikacin, Ceftazidime, Cefotaxime, Ofloxacin, Oxytetracycline, Streptomycin, Gentamycin and Imipenem) diluted in Muëller–Hinton Agar. Our proof-of-concept evaluation confirmed that the direct detection of more than one bacterium parallel to measuring MIC in samples is possible, which is validated using reference strains E. coli ATCC 25922, Klebsiella pneumoniae ATCC 13883, Pseudomonas aeruginosa ATCC 10145, and Staphylococcus aureus ATCC 12600 and with mastitis milk samples collected from Reading University Farm. When mixtures were tested, a MIC value was obtained that reflected the most resistant organism present (i.e., highest MIC), suggesting it may be possible to estimate a minimum effective antibiotic concentration for mixtures directly from samples containing multiple pathogens. We conclude that this simple miniaturized approach to the rapid simultaneous identification and antibiotic susceptibility testing may be suitable for directly testing agricultural samples, which is achieved through shrinking conventional tests into a simple “dip-and-incubate” device that can be 3D printed anywhere.

#45 Antibiotic Exposure and Risk of Cytomegalovirus Viremia Among Pediatric Hematopoietic Stem Cell Transplant Recipients at a Single Institution

Abstract Background Cytomegalovirus (CMV) causes substantial morbidity and mortality after hematopoietic stem cell transplantation (HCT), and antibiotic exposure after HCT is increasingly recognized as a risk for negative clinical outcomes. Recent studies identified an association between receipt of antibiotics with an anaerobic spectrum of activity and infection with cytomegalovirus (CMV) after HCT in adults. We sought to evaluate the association between anaerobic antibiotic exposure and CMV viremia in a well-characterized cohort of pediatric HCT recipients. Method We conducted a single-center retrospective cohort study of HCT recipients &amp;lt;18 years of age who underwent HCT at Duke University between 2000 and 2016. Routine pre-emptive surveillance testing for CMV was performed; CMV viremia was defined as a positive whole blood hybrid capture CMV DNA assay or quantitative plasma CMV PCR. We used log-logistic regression to evaluate associations between anaerobic antibiotic exposure (vancomycin, metronidazole, meropenem, piperacillin-tazobactam) and CMV viremia-free survival at 100 days after HCT. The first model considered anaerobic antibiotic exposure in the first 14 days after HCT as a binary variable. The second model considered anaerobic antibiotic exposure in the first 100 days as a time-varying variable; once a subject was exposed to a specific antibiotic, they were considered exposed for the remainder of the study period. Both models adjusted for year of HCT, age, race, HCT type and donor cell source, underlying diagnosis, conditioning regimen, CMV serostatus, and treatment for graft-versus-host-disease. Results Among 966 children, median (interquartile range) age was 6.5 (3.1, 11.5) years. Hematologic malignancy was the indication for transplantation in 417 (43%) subjects. Of 770 allogeneic HCT, 566 (74%) were from an umbilical cord blood donor and 204 (26%) were from a bone marrow donor. The majority of HCT were recipient CMV-seronegative and donor CMV-seronegative (R-/D-; 537, 56%), with 24 (2%) R-/D+, 270 (28%) R+/D-, and 135 (14%) R+/D+ transplants. Within the first 100 days after HCT, 692 (72%) children received vancomycin, 363 (38%) received metronidazole, 231 (24%) received meropenem, and 121 (13%) received piperacillin-tazobactam. Exposure to vancomycin (OR=0.86; 95% CI: 0.59, 1.26), metronidazole (OR=0.76; 95% CI: 0.53, 1.10), meropenem (OR=1.19; 95% CI: 0.74, 1.90), or piperacillin-tazobactam (OR=1.03; 95% CI: 0.55, 1.92) in the first 14 days after HCT was not associated with the risk of CMV viremia-free survival at 100 days. Similarly, we found no increased risk of CMV viremia with anaerobic antibiotic exposure in the first 100 days after HCT (vancomycin OR=0.90; 95% CI: 0.60, 1.34; metronidazole OR=0.80; 95% CI: 0.53, 1.21; meropenem OR=0.98; 95% CI: 0.60, 1.62; piperacillin-tazobactam OR=0.69; 95% CI: 0.38, 1.23). Conclusion In this study of pediatric HCT recipients, we did not find evidence of an association between anaerobic antibiotic exposures and CMV viremia risk. However, future pediatric and adult studies are warranted to evaluate this previously reported association in other populations, including studies evaluating for a possible role of the gut microbiome in modifying CMV viremia risk after HCT.

Relation of Right Atrial Strain to Mortality in Infants With Single Right Ventricles

We explored associations of surveillance testing in infants with single right ventricle (sRV) physiology with clinical outcomes. This prospective, single-center study included patients with sRV who had initial palliative surgery (September 2019 to December 2020). Echocardiograms and B-type naturetic peptide (BNP) obtained as a pair within 24hours as part of clinical care were included. The primary outcome was death/heart transplant. Secondary outcomes included interstage duration of milrinone use, hospital length of stay, and no digoxin use. sRV functional assessment (subjective grade, fractional area change, tricuspid annular plane systolic excursion, global longitudinal strain, right atrial strain [RAS]) was performed offline. Associations between echocardiography, BNP, and clinical outcomes were determined. Of 26 subjects (47 encounters), 20 had hypoplastic left heart syndrome (77%). Median age at data collection was 50days (interquartile range 26 to 90). In most encounters (73%), sRV function was subjectively normal. Median BNP was 332pg/ml (interquartile range 160 to 1,085). A total of 5 patients (19%) met the primary outcome and had lower RAS (14.1 vs 21.3, p=0.038), but all other parameters were similar to transplant-free survivors. RAS (16.1%, 0.83) had the highest area under curve, followed by global longitudinal strain (-14.4%, 0.77). Higher RAS was associated with fewer days on milrinone (coefficient -1.37, 95% confidence interval [CI] -2.54 to -0.20, p=0.02) and higher odds of digoxin use (odds ratio 1.09, 95% CI 1.01 to 1.18, p=0.047). Higher BNP was only associated with a lower odds of digoxin use (odds ratio 0.69, 95% CI 0.5 to 0.96, p=0.03). In conclusion, RAS is a potentially important imaging marker in infants with sRV and merits further investigation in larger studies.

Performance of the TaqMan COVID-19 Pooling Kit for detection of SARS-CoV-2 in asymptomatic and symptomatic populations.

Clinical evidence for asymptomatic cases of coronavirus disease (COVID-19) has reinforced the significance of effective surveillance testing programs. Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) assays are considered the ‘gold standard’ for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. However, the labor and resource requirements can be prohibitive with respect to large testing volumes associated with the pandemic. Pooled testing algorithms may serve to increase testing capacity with more efficient resource utilization. Due to the lack of carefully curated cohorts, there is limited evidence for the applicability of RT-PCR pooling in asymptomatic COVID-19 cases. In this study, we compared the analytical sensitivity of the TaqMan™ SARS-CoV-2 Pooling Assay to detect one positive sample in a pool of five anterior nares swabs in symptomatic and asymptomatic cohorts at an institute of higher education. Positive pools were deconvoluted and each individual sample was retested using the TaqPath™ COVID-19 Combo Kit. Both assays target the open reading frame (ORF) 1ab, nucleocapsid (N), and spike (S) gene of the strain that originated in Wuhan, Hubei, China. Qualitative results demonstrated absolute agreement between pooled and deconvoluted samples in both cohorts. Independent t-test performed on Ct shifts supported an insignificant difference between cohorts with p-values of 0.306 (Orf1ab), 0.147 (N), and 0.052 (S). All negative pools were correctly reported as negative. Pooled PCR testing up to five samples is a valid method for surveillance testing of students and staff in a university setting, especially when the prevalence is expected to be low.

Evaluation of Zika rapid tests as aids for clinical diagnosis and epidemic preparedness.

SummaryBackgroundDevelopment and evaluation of diagnostics for diseases of epidemic potential are often funded during epidemics, but not afterwards, leaving countries unprepared for the next epidemic. United Nations Children's Emergency Fund (UNICEF) partnered with the United States Agency for International Development (USAID) to address this important gap by investing in an advance purchase commitment (APC) mechanism to accelerate the development and evaluation of Zika rapid diagnostic tests (RDTs) for case detection and surveillance. This paper describes the performance evaluation of five Zika RDTs eligible for procurement.MethodsA network of European Union-funded ZikaPLAN sites in Africa, Asia, Latin America with access to relevant serum specimens were selected to evaluate RDTs developed for the UNICEF APC mechanism. A standardised protocol and evaluation panels were developed and a call for specimens for the evaluation panels issued to different sites. Each site contributed specimens to the evaluation from their biobank. Data were collated, analysed and presented to the UNICEF Procurement Review Group for review.FindingsThree RDTs met the criteria for UNICEF procurement of sensitivity and specificity of 85% against a refence standard. The sensitivity/specificity of the ChemBio anti-Zika Virus (ZIKV) immunoglobulin M (IgM) test was 86.4 %/86.7% and the ChemBio ZCD system for anti-ZIKV IgM was 79.0%/97.1%, anti-dengue virus (DENV) IgM 90.0%/89.2%, anti-Chikungunya virus (CHIKV) IgM 90.6%/97.2%. The sensitivity/specificity of the SD Biosensor anti-ZIKV IgM was 96.8 %/90.8%, anti-DENV IgM 71.8%/83.5%, the DENV nonstructural protein 1 (NS1) glycoprotein 90.0%/90.2%, anti- yellow fever virus (YFV) IgM 84.6%/92.4%, anti-CHIKV IgM 86.3%/97.5%.InterpretationThree RDTs fulfilled the performance thresholds set by WHO and were eligible for UNICEF procurement. These tests will improve the diagnosis of ZIKV and other arboviral infections as well as providing countries with better tools for surveillance and response to future epidemics.FundingThis work was supported by the USAID grant GHA-G-00-07-00007 and ZikaPLAN (European Union's Horizon 2020 Research and Innovation Programme under Grant Agreement No. 734584).

Measurement of Ground Vibration for Unpaved Bridge Approach Field Model on Soft Soil

The information and the data of the bridge approach condition is important because it allows designers to know the response of the soil once loaded with vehicles and respectable suggestion for correct engineering solutions to beat the matter. There are a few clarifications the reason of problem occurred at bridge approach was recently inspected by other researchers previously and one of the issues is a dissimilarity between the height of the bridge and road on the connection. The objective of this research is characterize and create techniques for field investigation to inspect the effect of vibration from vehicle loading at bridge approaches and this case might be referred to as a repetitive cyclic loading. The aim of this research is to investigate critical location of vibration at bridge approach model by the influence and effect from measurement tools. This research concentrated on constructed field model of the unpaved bridge approach model in Research Centre for Soft Soil Malaysia (RECESS), Universiti Tun Hussein Onn Malaysia (UTHM), Johor, Malaysia. A portable measurement equipment system with high sensitivity triaxial ICP accelerometer used to investigate and measure the effect of vibration loading at unpaved bridge approach field model. Piezoelectric (ICP) accelerometer is now preferable for researchers for the field surveillance or laboratory testing. From the analysis, it can be stated here that the vibration value increases as the speed and vibration level produced changes from L1 to L2. In the transverse direction, it is found that P1 values are larger than P2 to P6 values at both sites BAA and BAB. On the longitudinal direction, the farther away the plate compactor is from the bridge model connection, its value decreases and it is found that the D1 area has a higher vibration value compared to D2 to D5. It may be then, concluded that in this research it is similar to the previous research at the actual study site where the vibration value is high in the area 1m to 2m from the bridge connection.

Clinician utilization of a plasma-only, multiomic minimal residual disease (MRD) assay in 2,000 consecutive patients with colorectal cancer (CRC).

e15586 Background: Circulating tumor DNA (ctDNA) for detection of MRD in resected CRC is a prognostic factor for recurrence. However, current utilization of available commercial tests has not been investigated. We report real world clinician use of a validated, plasma-only, multiomic MRD assay (Guardant Reveal) in a large unselected CRC cohort. Methods: Results from Guardant Reveal MRD testing ordered for clinical care in the US were retrospectively queried for the first 2,000 consecutive CRC cases. Pts could be enrolled in a post-operative program to inform adjuvant treatment (PostOP, up to 3 tests within 3-16 weeks post-resection) or a surveillance program (SP) for recurrent tests post-treatment. Pts could have tests across both programs and/or one-time tests. All subsequent tests for the first 2,000 patients were included for analysis (data cut-off: 1/15/2022). Recurrent programs were analyzed for stage (stg) II/III only. Clinical factors were derived from test requisition forms. Results: 2681 tests from 1993 pts were analyzed; 7 pts were excluded due to missing cancer stage. Median age was 64 years (range: 21-65), 55% were male, most (94%) had stg II/III disease (Table). ctDNA was detected in 25% of all pts; detection increased with stage (Table) as expected. Among stg II/III pts, 330 (21%) had only PostOP test/s, 950 (51%) SP only, 54 (3%) had both PostOP and SP; the remainder had one-time test/s outside defined programs. In Stg II/III pts with &gt;1 PostOP test (26%/17% respectively), ctDNA was detected in 102/384 (27%), of whom 72% had it detected on the first test. The median time from surgery to first result was 5 weeks (10 weeks for a second result). 95% of all stg II/III pts had results from PostOP testing before week 12 post-resection. In Stg II/III pts with &gt;1 SP test (47%/54% respectively), ctDNA was detected in 244/1024 (24%), of whom 87% had it detected on a first test. The average time from date of surgery to first surveillance test was 305 days (median: 489, range:51-4618). Conclusions: ctDNA detection rates by a plasma-only multiomic MRD assay in this large CRC clinical cohort are similar to published rates. ctDNA orders by clinicians were most frequent in Stg II/III surveillance settings followed by PostOp, consistent with the population size of eligible patients for PostOp vs. Surveillance use-case. Importantly, nearly all pts tested PostOP had results prior to 12 weeks post-resection, which may inform adjuvant therapy decisions. These findings should be correlated with clinical outcomes to improve the utilization and utility of MRD testing in adjuvant management of CRC. [Table: see text]

The perception and emotional reaction to genetic test results in cancer patients in an immigrant enriched hospital.

e24128 Background: Genetic testing detects hereditary cancer syndromes and guides prophylactic surgery, intensive surveillance and family member testing. Despite its surge in use, research studies exploring the cancer patient’s perception and emotional reactions of their genetic test result is sparing. We hypothesized that the patient’s perception may be influenced by their ethnicity, educational level and English speaking status. Methods: Cancer patients who had genetic testing performed in the last 10 years were consented to take a questionnaire survey. The correctness of understanding their genetic test results were studied and compared among various ethnic groups, education levels and first spoken languages. We also evaluated the patient’s emotional reaction towards the result. Results: The data for the first 100 patients were analyzed. The primary tumor sites were breast (n = 71), gynecological (n = 16), gastrointestinal (n = 7), genitourinary (n = 5) and lung (n = 1). Eighteen patients were mutation carriers. The correctness in understanding mutation status was 65.7%, 54.2%, 70% and 45.5% in African American, Asian, Caucasian and Hispanics respectively. The correctness was 60%, 64.5% and 66.67% in patients with education levels of grade school or below, high school, or college or higher respectively. None of the 3 patients who carried a mutation with education level of grade school or lower understood the implications of their mutations. Details of correctness in understanding in patients with and without mutation are provided in the table. The correctness was 61.72% and 63.15% in English speaking vs non-English speaking patients. Patients could recall pre-test counseling in 76% and posttest counseling in 67% of cases. Among mutation carriers, 22.2% had anxiety or stressful feelings about the test result, while in patients with no mutation, 20.7% had anxiety/depression. 67% patients carried out prophylactic surgery as recommended. Conclusions: The correctness of understanding their genetic test results across all ethnic groups, education levels and language was below 70%. Patients with education level below grade school encountered in the immigrant population need more attention. Improvement in communication and patient education is imperative in order to carry out recommendations. Structured emotional support to the patient should always complement genetic counseling and testing.[Table: see text]

Unusual prevalence of cancer genetic mutations in a cohort of predominantly non-Caucasian cancer patients.

e22524 Background: Genetic testing has been applied increasingly widely in oncology, as detection of hereditary cancer syndromes can guide prophylactic surgery, intensive surveillance and family member testing. We hypothesized that the profile of mutation prevalence may be different from the general knowledge in patients with immigrant background. Methods: Cancer patients who have been treated in Maimonides hospital and have had a genetic test performed between 1/1/2010 until 1/31/2022 were eligible. Patients were randomly approached for consenting for the study. The results from the first 122 patients enrolled in this study were analyzed. Results: Among 122 patients, there were 86 breast, 22 GYN, 8 GI, 5 GU and 1 lung cancer. The ethnicities were African American (n = 38), Asian (n = 36), Caucasian (n = 32), Hispanic (n = 10) and mixed races (n = 6). Six patients had 2 primary cancers and 2 patients had 3 primary cancers. 25 patients (20.49 %) had germline mutations. A complete list of cancer type, mutation type, age of onset and cancer characteristics is shown in the table below. All of the 13 mutation positive breast cancer patients met the NCCN criteria for genetic testing, including 7 for age &lt; 50 and 6 with family history of breast cancer. Among the 2 patients with NF1 mutation, one had no skin change while the other had neurofibromatosis; both had family history, with pancreatic or breast cancer respectively. The patient with APC mutation had family history of numerous cancers including gastric, but no colon cancer. 48% patients had the onset of disease at older than 50 years old. Conclusions: In this multi-ethnicity cohort, 20.49% mutations were detected in patients who met the genetic testing criteria. A higher prevalence of BRCA 2 were found in both breast and ovarian cancer patients, and rare mutations of NF1, APC, FH and ATM were also detected. A large percentage had onset at an older age. More studies should be done in communities enriched with immigrants to gather further knowledge of unusual prevalence of genetic mutations, and an extensive panel for gene testing should be offered.[Table: see text]

A randomized phase III study assessing the efficacy of liquid biopsy in early diagnosis of recurrence and second malignancies in lung cancer survivors.

TPS10617 Background: Lung cancer survivors are highly enriched for extensive smoking histories and have an increased risk of subsequent primary cancers, including those of the larynx, mouth and throat, esophagus, pancreas, bladder, thyroid, stomach, small intestine, colon, rectum, and kidney. Guideline-concordant surveillance after definitive treatment for lung cancer consists of periodic chest CT scans, which do not visualize the majority of second malignancies that this population ultimately develops. Disadvantaged and minority patients are diagnosed with recurrence and second primary cancers at later stages due to reduced compliance with survivorship surveillance. To address these issues, we propose utilizing multi-cancer early detection (MCED) liquid biopsies. MCED liquid biopsies are part of a rapidly growing field of research that assesses parallel cancer screening for multiple cancer types with point of care blood, urine, or saliva sampling. We selected a methylation-based screening liquid biopsy for multiple reasons: 1) it has the highest PPV and specificity of any test clinically validated in the multi-cancer detection setting thus far, 2) it produces a tissue of origin, allowing for targeted workup of positive findings, and 3) it requires only a single test, which we believe will minimize attrition among vulnerable populations with decreased access to healthcare. We designed a 9,000-patient prospective, multi-institutional randomized clinical trial to assess the efficacy of liquid biopsy in early diagnosis of recurrence and second malignancies in lung cancer survivors. To ensure over 25% of participants are of minority status, we have recruited multiple community hospitals to the study in partnership with Memorial Sloan Kettering Cancer Center. Patients included in this study are survivors of non-metastatic non- small cell lung cancer, status-post definitive treatment (surgery or radiation) with no evidence of disease for at least one year. Participants will be randomized 1:1 to standard surveillance or standard surveillance plus six-monthly methylation-based liquid biopsy tests over a two-year study period, and strict guidelines on follow-up of positive liquid biopsy testing will be provided to reduce harms from false positives or over-diagnosis. Methods: The primary endpoint of this study is the incidence of late stage cancer (distant recurrence or new primary cancer of stage III/IV). Secondary endpoints include cancer-specific mortality, eligibility for definitive interventions once cancer is diagnosed, and utilization of liquid biopsy versus standard of care scans. This is the first randomized controlled trial of screening liquid biopsy in a survivorship population and the first trial utilizing liquid biopsy in a large minority population.

Differences in Motivating Factors for SARS-CoV-2 Vaccination and Perceptions of Infection Risk among Healthcare and EMS Personnel in South Carolina.

Although medical workers were prioritized to receive the coronavirus disease 2019 (COVID-19) vaccination, many have declined. Even though studies have investigated differences in COVID-19-related attitudes and vaccination for workers in hospitals and long-term care facilities, none have included emergency medical services (EMS) personnel. We investigated the association between type of medical worker (EMS vs healthcare worker [HCW]) and COVID-19 vaccination, vaccine beliefs, vaccine motivators, personal protection behaviors, and risk perceptions. The data for self-identified HCWs came from surveys distributed to randomly selected residents of South Carolina and EMS personnel recruited at a targeted surveillance testing event during the South Carolina EMS Symposium. Pearson χ2 and Fisher exact tests analyzed differences in the distribution of demographic characteristics and self-reported COVID-19 vaccination attitudes by medical workers. Multivariable logistic regression assessed the association between COVID-19 vaccination and type of medical worker, adjusting for age, sex, race, and frontline status, and assessed the associations among vaccine beliefs, vaccine motivators, personal protection behaviors, and risk perceptions by type of medical worker, adjusting for age, sex, race, frontline status, and vaccination status. Of the 126 respondents 57.9% were EMS, 42.1% were HCWs, and 73.6% of the cohort were self-reported frontline medical workers. Approximately two-thirds of respondents received a vaccine for COVID-19, with no significant differences between EMS and HCWs; however, EMS workers were significantly less likely to receive the vaccination out of concern about exposures at work/school (adjusted odds ratio [aOR] 0.22, 95% confidence interval [CI] 0.08-0.57), concern about exposures within the community (aOR 0.18, 95% CI 0.07-0.48), or to do their part to control the pandemic (aOR 0.20, 95% CI 0.06-0.69). EMS workers also were significantly less likely to wear a mask all/most of the time when outside the home (aOR 0.04, 95% CI 0.0-0.21) and less concerned about the spread of COVID-19 in their community as compared with HCWs (aOR 0.19, 95% CI 0.06-0.56). EMS personnel were significantly less concerned about the spread of COVID-19 in their community and significantly less likely to wear a mask all/most of the time while outside the home as compared with HCWs. Differences in the COVID-19-related attitudes and personal protection behaviors of EMS personnel should be used to develop targeted interventions to increase vaccine motivation and adherence to personal protection protocols.

Preliminary analysis of an expanded access study of the fixed-dose combination of pertuzumab (P) and trastuzumab (H) for subcutaneous injection (PH FDC SC) for at-home administration (admin) in patients (pts) with HER2-positive (HER2+) breast cancer (BC) during the COVID-19 pandemic.

1515 Background: Standard of care for HER2+ early/first-line metastatic BC (EBC/MBC) is P + H and concurrent chemotherapy (CT); PH FDC SC offers faster, more convenient admin vs intravenous (IV) P + H. COVID-19 has caused unprecedented strain on healthcare systems and disruption to cancer care; treatment (Tx) at home may: enable pts to continue cancer Tx; reduce exposure to COVID-19; free up hospital resources. This study’s main objectives: to enable continuity of care during COVID-19; to assess safety of PH FDC SC given at home. Methods: This is an ongoing single-arm, hybrid, decentralized clinical trial (NCT04395508). Pts with HER2+ EBC/MBC who completed concurrent CT with P + H IV and are receiving/about to receive maintenance P + H IV, PH FDC SC, or H SC are switched to PH FDC SC given at home by a home health nursing provider (HHNP) until disease progression, unacceptable toxicity, pt withdrawal, or physician recommendation (pts with EBC will complete ≤18 cycles). The study endpoint is safety. A subset of pts took part in HARRIET, a substudy of at-home cardiac surveillance with artificial intelligence-guided cardiac ultrasound and optional 6L ECG acquired by an HHNP. Results: Data for 114 pts (1 male) were available at cutoff (Jan 19, 2022): 18 (16%) completed Tx; 20 (18%) discontinued; 76 (67%) remain on study; 79 (69%) had a COVID-19 vaccine while on study. Median age was 49 years; pts were balanced between EBC (n = 55, 48%) and MBC (n = 59, 52%); received a median of 6 (EBC) and 8 (MBC) cycles; and were from metropolitan (n = 109), urban (n = 4), and rural (n = 1) areas. 11 pts tested COVID-19-positive during the Tx phase: 8 continued Tx after appropriate COVID-19 Tx and/or quarantine. Safety is summarized in the table. No new adverse events (AEs) emerged due to home admin. AEs of special interest were grade (gr) 1–2: admin-related reactions (n = 76, 67%), hypersensitivity (n = 5, 4%), cardiac dysfunction (n = 4, 4%), except 1 case of gr ≥3 diarrhea. AEs leading to study Tx discontinuation or interruption/dose reduction occurred in 3 (3%) and 15 (13%) pts. A subset of 7 pts completed at-home cardiac surveillance testing; quantitative assessment of left ventricular ejection fraction was feasible in 3 (43%); 5 (71%) preferred at-home surveillance to clinic. Conclusions: In this preliminary analysis, safety of PH FDC SC at home was consistent with the established P + H safety profile, indicating that PH FDC SC at home is a viable option for continuing BC care during and beyond COVID-19. Clinical trial information: NCT04395508. [Table: see text]

Development and implementation of a simple and rapid extraction-free saliva SARS-CoV-2 RT-LAMP workflow for workplace surveillance.

Effective management of the COVID-19 pandemic requires widespread and frequent testing of the population for SARS-CoV-2 infection. Saliva has emerged as an attractive alternative to nasopharyngeal samples for surveillance testing as it does not require specialized personnel or materials for its collection and can be easily provided by the patient. We have developed a simple, fast, and sensitive saliva-based testing workflow that requires minimal sample treatment and equipment. After sample inactivation, RNA is quickly released and stabilized in an optimized buffer, followed by reverse transcription loop-mediated isothermal amplification (RT-LAMP) and detection of positive samples using a colorimetric and/or fluorescent readout. The workflow was optimized using 1,670 negative samples collected from 172 different individuals over the course of 6 months. Each sample was spiked with 50 copies/μL of inactivated SARS-CoV-2 virus to monitor the efficiency of viral detection. Using pre-defined clinical samples, the test was determined to be 100% specific and 97% sensitive, with a limit of detection of 39 copies/mL. The method was successfully implemented in a CLIA laboratory setting for workplace surveillance and reporting. From April 2021-February 2022, more than 30,000 self-collected samples from 755 individuals were tested and 85 employees tested positive mainly during December and January, consistent with high infection rates in Massachusetts and nationwide.

Assessment of the Diagnostic Performance of a Novel SARS-CoV-2 Antigen Sealing Tube Test Strip (Colloidal Gold) as Point-of-Care Surveillance Test.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant outbreaks have highlighted the need of antigen-detecting rapid diagnostic tests (Ag-RDTs) that can be used at the point-of-care (POC). Although many Ag-RDTs have been approved for SARS-CoV-2 detection, studies demonstrating the clinical performance of Ag-RDTs against variants of concern, especially the new Omicron variant, are limited. The aim of this study was to evaluate the diagnostic sensitivity and specificity of the AMAZING COVID-19 Antigen Sealing Tube Test Strip (Colloidal Gold) in 584 early symptomatic and asymptomatic participants (age range 0–90 years). The performance of this Ag-RDT was assessed by comparing its results with reverse transcription RT-PCR (rRT-PCR). One hundred twenty positive samples were also analyzed with rRT-PCR to discriminate Omicron and Delta/Kappa variants (72.50% Omicron; 27.50% Delta/Kappa). Overall, the Ag-RDT showed high positive and negative percent values of 92.52% (95% CI, 86.61–95.95%) and 98.05% (95% CI, 96.41–98.95%), respectively, as well as an overall diagnostic accuracy of 96.92% (95% CI, 95.17–98.16%). Taken together, these data indicate that this inexpensive and simple-to-use Ag-RDT presents excellent analytical performance and can reliably detect Omicron and Delta/Kappa variants.

Pivoting Novel Exosome-Based Technologies for the Detection of SARS-CoV-2.

The National Institutes of Health (NIH) launched the Rapid Acceleration of Diagnostics (RADx) initiative to meet the needs for COVID-19 diagnostic and surveillance testing, and to speed its innovation in the development, commercialization, and implementation of new technologies and approaches. The RADx Radical (RADx-Rad) initiative is one component of the NIH RADx program which focuses on the development of new or non-traditional applications of existing approaches, to enhance their usability, accessibility, and/or accuracy for the detection of SARS-CoV-2. Exosomes are a subpopulation of extracellular vesicles (EVs) 30–140 nm in size, that are critical in cell-to-cell communication. The SARS-CoV-2 virus has similar physical and molecular properties as exosomes. Therefore, the novel tools and technologies that are currently in development for the isolation and detection of exosomes, may prove to be invaluable in screening for SARS-CoV-2 viral infection. Here, we describe how novel exosome-based technologies are being pivoted for the detection of SARS-CoV-2 and/or the diagnosis of COVID-19. Considerations for these technologies as they move toward clinical validation and commercially viable diagnostics is discussed along with their future potential. Ultimately, the technologies in development under the NIH RADx-Rad exosome-based non-traditional technologies toward multi-parametric and integrated approaches for SARS-CoV-2 program represent a significant advancement in diagnostic technology, and, due to a broad focus on the biophysical and biochemical properties of nanoparticles, the technologies have the potential to be further pivoted as tools for future infectious agents.

Rapid influenza molecular testing in secondary care and influenza surveillance in England: Any impact?

IntroductionThe use of rapid molecular testing for influenza diagnosis is becoming increasingly popular. Used at the point of care or in a clinical laboratory, these tests detect influenza A and B viruses, though many do not distinguish between influenza A subtypes. The UK Severe Influenza Surveillance System (USISS) collects surveillance data on laboratory‐confirmed influenza admissions to secondary care in England.This study set out to understand how rapid influenza molecular testing was being used and how it might influence the availability of subtyping data collected on influenza cases admitted to secondary care in England.MethodsAt the end of the 2017/2018 and 2018/2019 influenza seasons, a questionnaire was sent to all National Health Service Hospital Trusts in England to evaluate the use of rapid influenza testing. Surveillance data collected through USISS was analysed from 2011/2012 to 2020/2021.ResultsOf responding trusts, 42% (13/31) in 2017/2018 and 55% (9/17) in 2018/2019 used rapid influenza molecular tests, either alone or in combination with other testing. The majority of rapid tests used did not subtype the influenza A result, and limited follow‐up testing occurred.Surveillance data showed significant proportions of influenza A hospital and intensive care unit/high dependency unit admissions without subtyping information, increasing by approximately 35% between 2012/2013 and 2020/2021.ConclusionsThe use of rapid influenza molecular tests is a likely contributing factor to the large proportion of influenza A hospitalisations in England that were unsubtyped. Given their clear clinical advantages, further work must be done to reinforce these data for public health through integrated genomic surveillance.