Positive Test Research Articles

Risk of High-Grade Cervical Dysplasia in Older Patients With a Positive Human Papilloma Virus Cervical Screening Test

Introduction The Australian National Cervical Screening Program has mandated management algorithms that are uniform across all age groups, but evidence is emerging that perhaps the risk of high-grade squamous intraepithelial lesion (HSIL) may decrease in the postmenopausal period. Objective The aim of the study is to identify if patients ≥50 years of age referred to a tertiary colposcopy service have a different risk of HSIL or greater (+). Materials and Methods This is a retrospective cohort study of 3239 referrals to a hospital colposcopy clinic with a positive human papillomavirus (HPV) cervical screening test between December 2017 and May 2023. Patients were included if they were aged 25–74 years, had a cervix, and completed an outpatient colposcopic assessment. Medical records were analyzed to determine the incidence of HSIL+ for each age group and compared them using χ2 and multivariable regression. Results The overall incidence of invasive carcinoma was 0.93% and HSIL/adenocarcinoma-in-situ was 20.38%. Patients ≥50 years of age were less likely to have HSIL or greater diagnosed than those <30 (p < .0001) or those 30–49 (p < .0001), even after considering referral HPV subtype and reflex cytology (OR = 0.45, 95% CI = 0.34–0.59). The risk of invasive carcinoma in those aged ≥50 was no different than those aged 30–49 (p = .982). Conclusions We observed a lower incidence of HSIL or greater with increasing age even after considering referral HPV subtype and reflex cytology. As further data emerges regarding the risk of high-grade disease in those ≥50 years of age, refinement of the risk-based screening algorithm to account for advanced age may be required.

Application of Hierarchical Bayesian Models for Modeling Economic Costs in the Implementation of New Diagnostic Tests

The COVID-19 pandemic has highlighted the need for reliable and rapid diagnostic tests to control the spread of infection. The introduction of new rapid antigen tests often goes in tandem with the limited data availability, making it challenging to assess their performance at the initial phase of the pandemic. Sensitivity and specificity, the key performance characteristics provided by manufacturers, are typically derived under laboratory conditions and may not accurately reflect the tests' performance in field settings. We use the hierarchical Bayesian model to obtain their realistic estimates in real world conditions and show how it may be used in situations in which new tests with limited history are presented on the market. Proposed methodology allows for the efficient information pooling, thereby improving on the accuracy of parameter estimates for new tests. The results suggest that the application of hierarchical model on the Czech data led to a considerabile reduction in uncertainty associated with the parameter estimates as well as with potential economic cost implied by false positive test results. The model can thus assist in better informed decision-making and financial planning of both the government and corporations.

Arthroscopic Partial Meniscectomy in Adult Patient with Symptomatic Discoid Lateral Meniscus: A Case Report

Introduction: For many years, the discoid meniscus was synonymous with snapping knee syndrome. incidence of discoid lateral meniscus is estimated to be 0.4% to 17%, whereas the discoid medial meniscus is extremely rare (0.1% to 0.3%). It has been reported that about 20% of cases are bilateral. Patients with discoid lateral meniscus (DLM) often show normal plain radiography findings but may also show subtle indirect signs. Case Presentation: Female, 59 years old, complained of pain on her left knee after walking and climbing stairs for the last two months. On examination, the range of motion of knee joint was limited due to the pain for flexion more than 90°. Patient had medial joint line tenderness, and a McMurray test elicited pain on the lateral joint line. Radiographs of the left knee showed lateral joint space widening and high fibular head. Arthroscopic examination of the left knee confirmed the presence of discoid lateral menisci (DLM). Discussion: Discoid lateral meniscus (DLM), often referred to as "popping knee syndrome," is an abnormal variation of the meniscus, primarily affecting the lateral side and more common in young individuals. This condition increases the risk of knee injury, especially if the ligament attachment to the tibia is absent. In our case, radiographic findings and a positive McMurray test led to the diagnosis, confirmed by arthroscopy showing a complete DLM. While some recommend for total meniscectomy, studies suggest that partial meniscectomy can offer good initial results, though long-term outcomes may vary. Conclusion: In symptomatic DLM, surgical treatment is necessary to treat the patient. Arthroscopic partial meniscectomy is the preferred surgical procedure to treat symptomatic DLM. Keywords: Discoid lateral meniscus, arthroscopic menisectomy, WOMAC score

Burden of Respiratory Syncytial Virus-Associated Hospitalizations in US Adults, October 2016 to September 2023.

Respiratory syncytial virus (RSV) infection can cause severe illness in adults. However, there is considerable uncertainty in the burden of RSV-associated hospitalizations among adults prior to RSV vaccine introduction. To describe the demographic characteristics of adults hospitalized with laboratory-confirmed RSV and to estimate annual rates and numbers of RSV-associated hospitalizations, intensive care unit (ICU) admissions, and in-hospital deaths. This cross-sectional study used data from the RSV Hospitalization Surveillance Network (RSV-NET), a population-based surveillance platform that captures RSV-associated hospitalizations in 58 counties in 12 states, covering approximately 8% of the US population. The study period spanned 7 surveillance seasons from 2016-2017 through 2022-2023. Included cases from RSV-NET were nonpregnant hospitalized adults aged 18 years or older residing in the surveillance catchment area and with a positive RSV test result. Laboratory-confirmed RSV-associated hospitalization, defined as a positive RSV test result within 14 days before or during hospitalization. Hospitalization rates per 100 000 adult population, stratified by age group. After adjusting for test sensitivity and undertesting for RSV in adults hospitalized with acute respiratory illnesses, rates were extrapolated to the US population to estimate annual numbers of RSV-associated hospitalizations. Clinical outcome data were used to estimate RSV-associated ICU admissions and in-hospital deaths. From the 2016 to 2017 through the 2022 to 2023 RSV seasons, there were 16 575 RSV-associated hospitalizations in adults (median [IQR] age, 70 [58-81] years; 9641 females [58.2%]). Excluding the 2020 to 2021 and the 2021 to 2022 seasons, when the COVID-19 pandemic affected RSV circulation, hospitalization rates ranged from 48.9 (95% CI, 33.4-91.5) per 100 000 adults in 2016 to 2017 to 76.2 (95% CI, 55.2-122.7) per 100 000 adults in 2017 to 2018. Rates were lowest among adults aged 18 to 49 years (8.6 [95% CI, 5.7-16.8] per 100 000 adults in 2016-2017 to 13.1 [95% CI, 11.0-16.1] per 100 000 adults in 2022-2023) and highest among adults 75 years or older (244.7 [95% CI, 207.9-297.3] per 100 000 adults in 2022-2023 to 411.4 [95% CI, 292.1-695.4] per 100 000 adults in 2017-2018). Annual hospitalization estimates ranged from 123 000 (95% CI, 84 000-230 000) in 2016 to 2017 to 193 000 (95% CI, 140 000-311 000) in 2017 to 2018. Annual ICU admission estimates ranged from 24 400 (95% CI, 16 700-44 800) to 34 900 (95% CI, 25 500-55 600) for the same seasons. Estimated annual in-hospital deaths ranged from 4680 (95% CI, 3570-6820) in 2018 to 2019 to 8620 (95% CI, 6220-14 090) in 2017 to 2018. Adults 75 years or older accounted for 45.6% (range, 43.1%-48.8%) of all RSV-associated hospitalizations, 38.6% (range, 36.7%-41.0%) of all ICU admissions, and 58.7% (range, 51.9%-67.1%) of all in-hospital deaths. In this cross-sectional study of adults hospitalized with RSV before the 2023 introduction of RSV vaccines, RSV was associated with substantial burden of hospitalizations, ICU admissions, and in-hospital deaths in adults, with the highest rates occurring in adults 75 years or older. Increasing RSV vaccination of older adults has the potential to reduce associated hospitalizations and severe clinical outcomes.

Validation of algorithms to identify human immunodeficiency virus cases using administrative data in Manitoba.

Population-based administrative data are valuable for describing human immunodeficiency virus (HIV) cases, and their health status and outcomes. Our objective was to validate algorithms consisting of physician visits, hospitalizations, and antiretroviral prescriptions against positive confirmatory HIV laboratory tests to identify individuals living with HIV. The primary validation cohort consisted of adult Manitoban residents with at least 3years of health coverage between 2007 and 2018. Positive confirmatory HIV tests from the provincial laboratory were the reference standard. We evaluated 15 algorithms requiring 2 or 3years of administrative data (hospital, physician, and prescription records) to ascertain cases. Seven measures of accuracy were estimated: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), Youden's J, kappa, and area under the receiver operating characteristic curve (AUC) and their 95% confidence intervals. Validity was estimated for pregnantfemales. The primary validation cohort included 966,507 individuals, of whom 1452 (0.2%) were HIV cases. Algorithm sensitivity ranged from 82.8% to 97.5%. PPV ranged from 51.8% to 97.8%. Youden's J ranged from 0.83 to 0.97. Kappa ranged from 0.68 to 0.93. AUC ranged from 0.91 to 0.99. Researchers have a range of algorithms to ascertain HIV cases in administrative data; selection of an appropriate algorithm depends on the user goal. To maximize performance to distinguish HIV cases and non-cases while minimizing data requirements, an algorithm based on three or more physician visits in 2years is recommended. Further validation in other provinces and territories will assess the generalizability of these findings.

Abstract B018: Plasma-based circulating tumor tissue modified viral (TTMV)-HPV DNA for detection of recurrent HPV-driven anal cancer

Abstract Purpose: Squamous cell carcinoma of the anus (SCCA) is primarily driven by human papillomavirus (HPV) infection. Up to 30% of patients experience recurrence, necessitating improved surveillance strategies. Liquid biopsies have shown promise as a tool in oncology. This study investigates the clinical performance of circulating tumor tissue modified viral (TTMV)- HPV DNA in the post-treatment surveillance of SCCA. Patients and methods: This central IRB-approved retrospective cohort study included 117 patients diagnosed with HPV-driven SCCA from seven U.S. centers who had ≥1 TTMV-HPV DNA tests (NavDx®, Naveris, Inc., Waltham, MA) performed between March 2020 and June 2024. TTMV-HPV DNA for HPV subtypes 16, 18, 31, 33, and 35 were analyzed using droplet digital PCR. The diagnostic accuracy of TTMV-HPV DNA was evaluated by comparing test results with clinical evidence of SCCA recurrence determined through anoscopy, radiology, and/or tissue biopsy. Recurrence is defined as either a positive biopsy or subsequent salvage therapy. Results: Patients were primarily female (73%) with a median age 63 years. Median follow-up after initial treatment was 19 months. Forty-seven patients (40%) had pretreatment TTMV-HPV DNA testing, with a baseline detectability of 85.1% (40/47, 95% CI: 74.9–95.3). Of these, 24 were re-tested within 3 months post-treatment and 18 had undetectable TTMV-HPV DNA (75%). Those patients whose scores became undetectable had significantly longer recurrence-free survival than those whose scores remained detectable (log-rank test, p=0.01). One hundred and four patients (89%) underwent post-treatment testing, of which 91 provided relevant data for the analysis. Of these 91 patients, 27 (29.7%) experienced recurrence. Post-treatment testing demonstrated a per- patient sensitivity of 85.7% (24/28, 95% CI: 72.8-98.7). Of four patients with a false negative test, only one had biopsy-confirmed recurrence, whereas the remaining recurrences were not biopsied prior to starting salvage treatment. The positive predictive value of a single positive test was 97.6% (40/41; 95% CI: 92.8–100.0). One patient remains in active follow-up. Of the true positive post-treatment tests, 58% (14/24) predicted recurrence before clinical detection, with a median lead time of 59 days (range: 10–536). There were 141 negative post-treatment tests across 66 patients. This yielded a per-test specificity and negative predictive value of 99.3% (136/137, 95% CI: 97.8-100.0) and 97.2% (136/140, 95% CI: 94.9-99.9), respectively. Indeterminate TTMV-HPV DNA tests were rare (5/268,1.9%). However, clinically indeterminate findings (CIFs) were common, with 141 post-treatment CIFs identified across 52/117 patients (44.4%). TTMV-HPV DNA testing was able to correctly predict recurrence status in 94.3% of CIF cases. Conclusion: TTMV-HPV DNA testing is a sensitive and specific surveillance method for detecting early recurrence of HPV-driven SCCA. Citation Format: Shane Lloyd, Rafi Kabarriti, James Jabalee, Tyler Slater, Corbin Jacobs, Sean Inocencio, Michael Rutenberg, Chance Matthiesen, Kasha Neff, Gene-Fu F Liu, Tiffany M Juarez, Catherine DV Fitz, Stanley Liauw. Plasma-based circulating tumor tissue modified viral (TTMV)-HPV DNA for detection of recurrent HPV-driven anal cancer [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B018.

Abstract B022: Immediate post-treatment detection of minimal residual disease in HPV-Driven oropharyngeal cancer is associated with high risk of recurrence

Abstract Purpose: Detecting minimal residual disease (MRD) has emerged as a key strategy in oncology for identifying those at high risk of relapse. Circulating tumor tissue modified viral (TTMV)-HPV DNA has emerged as a promising biomarker in HPV-driven oropharyngeal cancer. Prior studies have largely focused on detection beyond three months post-treatment. This study evaluated the ability of TTMV-HPV DNA to detect MRD immediately after initial or salvage treatment. Patients and Methods: This IRB-approved, retrospective cohort study included 171 patients across eight U.S. centers who had pathologically confirmed HPV-driven oropharyngeal cancer. Patients received at least one TTMV-HPV DNA test (NavDx®, Naveris, Inc.) done between zero and three months of treatment between February 2020 and April 2022. Minimum four months of follow-up was required for patient inclusion. Test results were correlated with physician-reported exams, imaging studies, and biopsies. Results: Patients were primarily White (94%) and male (86%) and were a median age at diagnosis of 60 years (range: 31 - 81). Primary tumors were located in the tonsil or base of tongue (94%) and were mostly T1-T2 (77%), N1 (66%), and M0 (98%). Patients had a median follow-up of 17 months after the completion of initial definitive treatment (range: 4-96 months). In this cohort, 198 tests conducted in 171 patients were evaluable. A total of 14 patients had both biopsy-confirmed pathologic recurrences and relevant post-treatment testing data in relation to the recurrence, with a median disease-free interval of three months (range: 1-16). Within this cohort, TTMV-HPV DNA testing demonstrated a per-patient sensitivity of 85.7% (12/14, 95% CI: 67-100). The positive predictive value (PPV) of a single TTMV-HPV DNA test within the first three months following treatment was 86.7% (13/15, 95% CI: 69.5-100). Six of the positive tests (46.2%) preceded clinical recurrence detection by a median lead-time of 36 days (range: 21-97). Test positivity following initial definitive treatment was significantly associated with worse recurrence-free survival (log-rank test, p<0.0001; hazard ratio: 21). The two patients with false positive test results had their TTMV-HPV DNA testing performed just four days after completing CRT. Their test scores returned to negative on the subsequent test, and both patients have remained disease-free. Of the 157 patients who remained TTMV-HPV DNA negative throughout the duration of follow-up, only two (1.3%) had biopsy-confirmed, HPV-positive recurrence before or within three months of a negative test. The specificity and negative predictive value (NPV) per-test were each 98.9% (181/183, 95% CI: 97.4-100). Conclusion: TTMV-HPV DNA demonstrates strong potential as a prognostic biomarker for detecting MRD in the immediate post-treatment setting, with a high PPV and NPV for recurrence. These findings support the integration of TTMV-HPV DNA into routine surveillance protocols to enhance early detection of recurrence and guide timely interventions. Citation Format: Scott A Roof, James Jabalee, Eleni M Rettig, Rocco Ferrandino, Sida Chen, Marshall R Posner, Krzysztof J Misiukiewicz, Eric M Gender, Raymond L Chai, John Sims, Elaine Thrash, Scott J Stern, Noah S Kalman, Sreenija Yarlagadda, Adam Raben, Lydia Clements, Abie Mendelsohn, John M Kaczmar, Yadav Pandey, Mihir Bhayani, Catherine DV Fitz, Glenn J Hanna. Immediate post-treatment detection of minimal residual disease in HPV-Driven oropharyngeal cancer is associated with high risk of recurrence [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B022.

Solitary Peutz-Jeghers polyp harboring a focus of high-grade dysplasia in the colon: a case report and literature review.

A solitary Peutz-Jeghers (PJ) polyp is a rare hamartomatous lesion without an associated PJ syndrome. However, little is known regarding malignancy arising in solitary PJ polyps. Here, we report a case of a solitary colonic PJ polyp with focal dysplasia. A 45-year-old asymptomatic man underwent total colonoscopy following a positive fecal occult blood test. The patient had no history of mucocutaneous pigmentation or family history of PJ syndrome. A 20mm erythematous pedunculated polyp was observed in the sigmoid colon. Magnified endoscopy revealed a tubular or branch-like pit pattern with localized areas of irregular pits. These findings were suggestive of colorectal adenoma with high-grade dysplasia, and endoscopic mucosal resection was performed. Histopathological examination revealed arborizing proliferation of hyperplastic epithelia with smooth muscle bundles. In addition, a small number of irregular crypts with high-grade dysplasia were observed in the hyperplastic epithelium. Based on these histological findings, we finally diagnosed the patient with a solitary colonic PJ polyp with high-grade dysplasia. The present case suggests that solitary colonic PJ polyps may harbor dysplastic changes and require pathological evaluation with en bloc resection of the polyps.

EGS SO18 - Entero-enteric intussusception secondary to a capillary haemangioma of the small bowel: A case of a diagnostic conundrum

Abstract Background This is a case of a 50 year-old female who presented with acute on chronic abdominal pain, and she was intra-operatively diagnosed with entero-enteric intussusception secondary to a large small bowel tumour . The video demonstrates the findings during the diagnostic laparoscopy. The lead point appeared to be a tumour and histopathology confirmed it is a benign capillary haemangioma. The patient had a long standing history of abdominal pain that was previously investigated on multiple occasions, but without a definitive diagnosis. Method This is an interesting case of a challenging diagnosis of a rare disease. The patient has been suffering for four years with unexplained upper abdominal pain not associated with weight loss, rectal bleed, or change in bowel habit, but had occasional anaemia. The patient had a normal abdominal US, multiple CTs where she was found to have a right renal stone and an OGD that showed gastritis and positive CLO test initially. A repeat OGD and colonoscopy were negative. While the patient was awaiting further investigations for profound iron deficiency anaemia she presented with acute abdomen and required emergency surgery. Results The patient presented to ED with excruciating colicky pain for one day, one episode of melena and nausea. She was haemodynamically stable, peritonitic with increased inflammatory markers, hb 86 g/dL and lactate of 2 mmol/L. The CT abdomen and pelvis showed small bowel intussusception with possible ischemia, therefore the patient underwent an emergency operation.The laparoscopy showed small bowel intussusception and the patient underwent mini laparotomy. The intussusception was reduced, the small bowel was viable and the lead point was a large size tumour.The patient underwent small bowel resection and primary anastomosis, and made good post operative recovery. Conclusion Rare conditions are hard to diagnose. Small bowel intussusception is rare and in adults is usually linked to serious underlying pathology. Capillary haemangioma of the small bowel is very rare too. The patient's symptoms and occassional anaemia can now be explained. Although the patient went through an appropriate work up at the time, her symptoms remained unexplained to some extent or they were linked to other potential causes. Only when the anaemia became profound the patient warranted further investigations. In retrospect, capsule endoscopy would have been inevitable, however the patient became acutely unwell and required an emergency surgery.

Case report: A novel JAK3 homozygous variant in a patient with severe combined immunodeficiency and persistent COVID-19

Inborn errors of immunity (IEI) encompass a broad range of disorders with heterogeneous clinical presentations, often leading to challenges in early diagnosis. This study presents a case of a Brazilian patient with a T-B+NK- severe combined immunodeficiency (SCID) diagnosed at the age of 6 months when was admitted to the hospital due to multiple infectious diseases. Despite undergoing hematopoietic stem cell transplantation (HSCT), the patient had recurrent infections, requiring constant hospital care, including IgG infusions and several antibiotic treatments for the following months. One year after HSCT, presenting mixed chimerism, the patient tested positive for SARS-CoV-2 in nasopharyngeal, duodenum, and intestine samples, with persistent positive tests over a six-month period. Whole exome sequencing identified a private homozygous missense variant (c.1202T>C; p.Leu401Pro) in the Janus Kinase 3 (JAK3) gene. This substitution is located in a highly conserved position, and different bioinformatic variant effect predictors classified the variant as damaging. In silico structural analysis suggested that the variant led to increased structural instability, disrupting the hydrophobic interactions within the SH2 domain, thereby influencing the neighboring residues and potentially altering the interaction between JAK3 and gamma chain (γc) intracellular receptors. This study provides evidence for the novel pathogenicity classification of the variant and highlights the importance of the JAK3 and SH2 domain modulating protein function and their contribution to the SCID pathogenesis.

Abstract A074: Early detection of breast implant associated anaplastic large cell lymphoma by multiplex lateral flow assay of CD30 and IL-10

Abstract Introduction: More than 1300 women have developed a unique breast implant associated anaplastic large cell lymphoma (BIA-ALCL) around breast implants. BIA-ALCL presents as an accumulation of fluid (seroma) a median of 9 years after implant placement. When detected early, survival with surgery alone is nearly 100%. Remaining patients present with masses and/or lymph node metastases requiring radiation, chemotherapy and/or immunotherapy and fatalities have occurred. Methods: Preliminary studies identified CD30 and IL-10 as the most sensitive and specific biomarkers for BIA-ALCL in seroma fluids. Therefore, we constructed a multiplex LFA to detect both CD30 and IL-10 in 30 mL seroma fluid within 20 minutes. LFA is a point of care immunoassay using capture and detection antibodies that detect separate epitopes of the target molecule. The detection antibody is linked to a colored particle; in this multiplex assay CD30 antibody was linked to blue and IL-10 to red particles. Separate positive test lines (blue and red) indicate presence of CD30 or IL-10. A control line confirms migration of the seroma fluid past the test lines. To determine the dynamic range of sensitivity we spiked recombinant CD30 and IL-10 into benign seromas. Test and control lines were quantitated with NIH Image J software and ratios of test line to control line calculate for each sample. Forty-eight hour supernatants of supernatants of BIA-ALCL lines TLBR1 and TLBR2 were tested for IL-10 and CD30. Fifteen patients, 8 with BIA-ALCL and 7 with benign seromas provided consent for testing of their seroma fluids. Results: Multiplex CD30/IL10 LFA produced positive test lines for neat and 1:10 dilutions of 48 hour supernatnats of BIA-ALCL lines TLBR1 and TLBR2. Both IL-10 and CD-30 could be detected on the multiplex LFA strip using a 1:3 dilution of seroma fluids. The multiplex LFA shows both IL-10 and CD30 are significantly higher in malignant samples (IL-10 TL/CL: malignant, 0.2±0.16 n=8 vs benign, 0.004±0.007 n=7, p<0.05; CD30 TL/CL: malignant, 0.38±0.2 vs benign, 0.02±0.02, p<0.001, two-way ANOVA). Importantly, when either IL-10 or CD30 yields a faint positive test line, the other is not detected reducing the possibility of false positives. Conclusions: The CD30/IL-10 multiplex LFA had 100% positive and negative predictive value in this pilot study. The assay was able to distinguish lymphoma from recurrent breast cancer and more common benign seromas. The use of this multiplex assay mitigates positive false positive results from more sensitive CD30 LFA which has been detected in some benign seromas. This LFA will potentially allow early pre-operative detection of ALCL allowing surgeons to plan their surgical approach. The LFA can replace more costly time-consuming flow cytometry, immunohistochemistry, cyto- and histopathologic studies which require at least 10 ml of fluid. The LFA can be performed outside of medical centers in rural and underserved areas. A larger prospective multicenter study including intra-operative sampling is planned to validate these results. Citation Format: Peng Xu, Katerina Kourentzi, Richard Willson, Marshall Kadin. Early detection of breast implant associated anaplastic large cell lymphoma by multiplex lateral flow assay of CD30 and IL-10 [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A074.

Participation in the National Bowel Cancer Screening Program by people with severe mental illness, Australia, 2006-2019: a national data linkage study.

To compare rates of participation in the National Bowel Cancer Screening Program (NBCSP) and follow-up for people with severe mental illness with those for people without severe mental illness or not prescribed antidepressants. Retrospective cohort study; analysis of de-identified linked NBCSP, Pharmaceutical Benefits Scheme (PBS), and Medicare Benefits Schedule (MBS) data. Australia, 2006-2019. People aged 50-74 years (NBCSP-eligible) with severe mental illness, defined as those dispensed two or more prescriptions for second generation antipsychotics or for lithium (PBS data), and a random sample of people aged 50-74 years eligible for Medicare-subsidised services but never prescribed psychotropic medications (antipsychotics, lithium, antidepressants). NBCSP participation (returned faecal occult blood test sample), valid test result, positive test result, and follow-up colonoscopy rates. A total of 119 475 people with severe mental illness and 1 090 574 control group people were included in our analyses. The proportion of women was larger in the severe mental illness group (51.3%) than the control group (48.7%), as were the proportions who lived in inner regional areas (23.5% v 19.1%) or in areas in the lowest socio-economic quintile (21.8% v 14.7%). The NBCSP participation rate was lower among people with severe mental illness (adjusted incidence rate ratio [IRR], 0.70; 95% confidence interval [CI], 0.69-0.84). The proportion of valid test results was smaller for people with severe mental illness (95.9% v 98.7%; adjusted IRR, 0.97; 95% CI, 0.96-0.99), and the positive test result proportion larger (12.3% v 6.6%; adjusted IRR, 2.01; 95%CI, 1.94-2.09). The proportion of positive test results followed by colonoscopy was smaller for people with severe mental illness (71.7% v 82.6%; adjusted IRR, 0.88; 95% CI, 0.85-0.92). People with severe mental illness were less likely to participate in the NBCSP or to undergo colonoscopy after a positive test result than other Australians. These differences may contribute to higher colorectal cancer mortality among people with severe mental illness. The contributions of differences in cancer stage at diagnosis and subsequent treatment to higher colorectal cancer mortality require further study.

The disappearing COVID-Naïve Population and comparative Roche vs. Abbott Test sensitivity: evidence from antibody seroprevalence in Milwaukee County, Wisconsin.

We study the prevalence of SARS-CoV-2 antibodies in a diverse population in Milwaukee County, Wisconsin from May 2021 to June 2022. We find that 99.4% (523/526) of the participants had positive results for antibodies to the SARS CoV2 spike protein over April-June 2022, soon after the early-2022 Omicron surge. Positive tests for spike protein antibodies were very high (86%; 19/22) even among unvaccinated persons who reported no knowledge of prior infection. Thus, by mid-2022, almost all persons were no longer COVID-naïve, defined as vaccination, infection (often without symptoms), or both. Nucleocapsid antibody tests, especially the Abbott test, were far less sensitive than spike protein tests, and Abbott test sensitivity faded with time since infection. Thus, studies which rely on nucleocapsid tests will understate prior infection rates. We also report large sample evidence on the performance of the Abbott and Roche spike and nucleocapsid protein tests in capturing prior vaccination, infection, or both. The Roche spike protein test outperforms the Abbott spike test, and the Roche nucleocapsid test greatly outperforms the Abbott nucleocapsid test.

Identifying Hemolytic Disease of the Fetus and Newborn within a Large Integrated Health Care System.

This study aims to identify hemolytic disease of the fetus and newborn (HDFN) pregnancies using electronic health records (EHRs) from a large integrated health care system. A retrospective cohort study was performed among pregnant patients receiving obstetrical care at Kaiser Permanente Southern California health care system between January 1, 2008, and June 30, 2022. Using structured (diagnostic/procedural codes, medication, and laboratory records) and unstructured (clinical notes analyzed via natural language processing) data abstracted from EHRs, we extracted HDFN-specific "indicators" (maternal positive antibody test and abnormal antibody titer, maternal/infant HDFN diagnosis and blood transfusion, hydrops fetalis, infant intravenous immunoglobulin [IVIG] treatment, jaundice/phototherapy, and first administrated Rho[D] Immune Globulin) to identify potential HDFN pregnancies. Chart reviews and adjudication were then performed on select combinations of indicators for case ascertainment. HDFN due to ABO alloimmunization alone was excluded. The HDFN frequency and proportion of each combination were fully analyzed. Among the 464,711 eligible pregnancies, a total of 136 pregnancies were confirmed as HDFN pregnancies. The percentage of the HDFN-specific indicators ranged from 0.02% (infant IVIG treatment) to 34.53% (infant jaundice/phototherapy) among the eligible pregnancies, and 32.35% (infant IVIG treatment) to 100% (maternal positive antibody test) among the 136 confirmed HDFN pregnancies. Four combination groups of four indicators, four combination groups of five indicators, and the unique combination of six indicators showed 100% of HDFN pregnancies, while 80.88% of confirmed HDFN pregnancies had the indicator combination of maternal positive antibody test, maternal/infant HDFN diagnosis, and infant jaundice/phototherapy. We successfully identified HDFN pregnancies by leveraging a combination of medical indicators extracted from structured and unstructured data that may be used in future pharmacoepidemiologic studies. Traditional indicators (positive antibody test results, high titers, and clinical diagnosis codes) alone did not accurately identify HDFN pregnancies, highlighting an unmet need for improved practices in HDFN coding. · A case ascertainment method was developed to identify HDFN from structured and unstructured data.. · The method used in this study may be used in future pharmacoepidemiologic studies.. · The study highlighted an unmet need for improved practices in HDFN coding..

Long-Term outcomes after stress echocardiography in real world practice: five-year follow-up of the UK Evarest study.

Stress echocardiography is widely used to assess patients with chest pain. The clinical value of a positive or negative test result to inform on likely longer-term outcomes when applied in real world practice across a healthcare system has not been previously reported. 5503 patients recruited across 32 UK NHS hospitals between 2018 and 2022, participating in the EVAREST/BSE-NSTEP prospective cohort study, with data on medical outcomes up to 2023 available from NHS England were included in analysis. Stress echocardiography results were related to outcomes, including death, procedures, hospital admissions and relevant cardiovascular diagnoses, based on Kaplan-Meier analysis and Cox proportional hazard ratios. Median follow-up was 829 days (IQR 224-1434). A positive stress echocardiogram was associated with a greater risk of myocardial infarction (HR 2.71, 95% CI 1.73-4.24, P<0.001), and a composite endpoint of cardiac-related mortality and myocardial infarction (HR 2.03, 95% CI 1.41-2.93, P<0.001). Hazard ratios increased with ischaemic burden. A negative stress echocardiogram identified an event-free 'warranty period' of at least five years in patients with no prior history of coronary artery disease, and four years for those with disease. In real-world practice, the degree of myocardial ischaemia recorded by clinicians at stress echocardiography correctly categorises risk of future events over the next five years. Reporting a stress echocardiogram as negative correctly identifies patients with no greater than a background risk of cardiovascular events over a similar time period.

Abstract 4138528: Clinical Characteristics of Five Different Endotypes from Coronary Reactivity Testing, and the Emergence of Sex Patterns in Coronary Microvascular Dysfunction

Background: The common preconception is that non-obstructive coronary artery disease(NOCAD) predominantly affects females with little to no cardiac risk factors. However, it is unclear whether there is a significant difference in baseline characteristics between those with a positive vs negative coronary reactivity testing(CRT) result. Furthermore, CRT explores multiple pathophysiological mechanisms which make a positive result nuanced. This study identifies 5 different endotypes based on CRT results, aiming to identify phenotypic characteristics that correlate with these endotypes. METHODS: 409 patients were included in a cohort study, representing all patients referred for CRT to a tertiary referral centre for NOCAD, between 2016-2024. Patients underwent protocol CRT of coronary flow reserve(CFR) and index of microvascular resistance(IMR) measurements following adenosine infusion(140mcg/kg/min) and bolus acetylcholine(100mcg). Results were compared by positive vs negative CRT, normal vs abnormal CFR/IMR, and by 5 different endotypes identified from CRT result combinations. RESULTS: There was no significant difference in clinical characteristics between the positive vs negative CRT result groups. However, with further stratification, there were significant sex differences and cardiac risk profile differences in CFR and IMR results. There was a greater proportion of females in the abnormal (low) CFR group(p&lt;0.001), and higher burden of cardiac risk factors in the abnormal (high) IMR group(p&lt;0.001). The highest burden of cardiac risk factors was seen in the 'Traditional Coronary Microvascular Dysfunction (CMD)' endotype, defined as those with abnormal(low) CFR and abnormal(high) IMR. The 'Functional CMD' endotype was characterised by younger females, whilst the 'Compensated CMD' and 'Coronary spasm' endotype showed no sex difference. The normal CFR and normal IMR endotype reflected the referred population(Figure 1). CONCLUSION: There is an emergence of clinical phenotypes according to the five coronary reactivity testing endotypes. Lower CFR appears to be a more “female pattern” of microvascular dysfunction. Endotypes reflect underlying pathology and may provide mechanistic explanations for sex differences in the microvascular dysfunction types of NOCAD, whilst explaining the lack of sex differences in other types. Further detailed understanding of CRT endotypes will allow us to understand the mechanistic differences in cardiovascular outcomes between males and females.

Abstract 4132249: Preoperative identification of respiratory viral genomes in the trachea but not in the nasopharynx is a risk factor for postoperative pulmonary hypertension in patients with congenital cardiac communications

Introduction: Pulmonary vascular remodeling is a key determinant of outcomes in patients undergoing surgery for congenital cardiac communications (CCCs). Respiratory epithelial cells infected by viruses express cytokines and growth factors with potential impact on airway and vascular remodeling. Hypothesis: Preoperative exposure to respiratory viruses renders CCC patients susceptible to postoperative pulmonary hypertension. Aims: To investigate if asymptomatic patients carrying respiratory viral genomes (RVGs) in the airways are at risk for pulmonary hypertension following cardiac surgery. To analyze the role of postoperative inflammatory reaction. Methods: The study comprised patients with unrestrictive CCCs undergoing surgery under cardiopulmonary bypass (CPB). In the absence of any signs of recent infection, RVGs were searched for in nasopharyngeal aspirates 2-3 days before surgery, and in tracheal aspirates collected in the operating room (RT-PCR, panel for 19 viruses). Serum levels of 36 inflammatory proteins were measured by chemiluminescence preoperatively and 4 hours post CPB. Pulmonary/systemic mean arterial pressure ratio (PAP/SAP) computed during the first 12 hours postoperatively (invasive assessment) was defined as the study outcome. A cutoff level was set at 0.40. Results: Sixty patients were enrolled (age 11 [7-16] months, median with interquartile range). Preoperative PAP/SAP was 0.78 (0.63-0.88). RVGs were present in nasopharyngeal and tracheal aspirates in 64% and 38% of patients, respectively. The presence of RVGs in tracheal aspirates was associated with an upward shift of postoperative PAP/SAP curve (p=0.006). The same was not observed for positive tests in nasopharyngeal aspirates (p=0.343). Of all factors analyzed as possible predictors of postoperative PAP/SAP &gt;0.40, only preoperative peripheral oxygen saturation and the presence of RVGs in the trachea were selected at multivariate analysis (respective OR with 95% CI, 0.40 [0.23-0.72] and 4.42 [1.17-16.78]. Heightened post-CPB levels of interleukin-1 receptor antagonist and chemokines MIF and MCP-1 were found to increase the risk of having a PAP/SAP &gt;0.40 in RVG carriers (respective OR with 95% CI, 2.04 [1.09-3.81], 2.34 [1.15-4.74] and 2.18 [1.07-4.43]. Conclusion: The observed relation of postoperative hemodynamics to respiratory viruses and post-CPB inflammatory reaction may have pathophysiological and therapeutic implications in pulmonary hypertension associated with congenital heart disease.

Can self-testing be enhanced to hasten safe return of healthcare workers in pandemics? Random order, open label trial using two manufacturers' SARS-CoV-2 lateral flow devices concurrently and nested viral culture study.

Covid-19 healthcare worker testing, isolation and quarantine policies had to balance risks to patients from the virus and from staff absence. The emergence of the Omicron variant led to dangerous levels of key-worker absence globally. We evaluated whether using two manufacturers' lateral flow tests (LFTs) concurrently improved SARS-CoV-2 Omicron detection significantly and was acceptable to hospital staff. In a nested study, to understand risks of return to work after a 5-day isolation/quarantine period, we examined virus culture 5-7 days after positive test or significant exposure. Fully-vaccinated Liverpool (UK) University Hospitals staff participated (February-May 2022) in a random-order, open-label trial testing whether dual LFTs improved SARS-CoV-2 detection, and whether dual swabbing was acceptable to users. Participants used nose-throat swab Innova and nose-only swab Orient Gene LFTs in daily randomised order for 10 days. A user-experience questionnaire was administered on exit. Selected participants gave swabs for viral culture on days 5-7 after symptom onset or first positive test. Cultures were considered positive if cytopathic effect was apparent or SARS-CoV-2 N gene sub-genomic RNA was detected. Two hundred and twenty-six individuals reported 1466 pairs of LFT results. Tests disagreed in 127 cases (8.7%). Orient Gene was more likely (78 cf. 49; OR: 2.1, 1.1-4.1; P = 0.03) to be positive. If Innova was swabbed second, it was less likely to agree with a positive Orient Gene result (OR: 2.7, 1.3-5.2; P = 0.005); swabbing first with Innova made no significant difference (OR: 1.1, 0.5-2.3; P = 0.85). Orient Gene positive Innova negative result-pairs became more frequent over time (OR: 1.2, 1.1-1.3; P < 0.001). Of individuals completing the exit questionnaire, 90.7% reported dual swabbing was easy, 57.1% said it was no barrier to their daily routine and 65.6% preferred dual testing. Respondents had more confidence in dual versus single test results. Viral cultures from days 5-7 were positive for 6/31 (19.4%, 7.5%-37.5%) and indeterminate for 11/31 (35.5%, 19.2%-54.6%) LFT-positive participants, indicating they were likely still infectious. Dual brand testing increased LFT detection of SARS-CoV-2 antigen by a small but meaningful margin and was acceptable to hospital workers. Viral cultures demonstrated that policies recommending safe return to work ~ 5 days after Omicron infection/exposure were flawed. Key-workers should be prepared for dynamic self-testing protocols in future pandemics. https://www.isrctn.com/ISRCTN47058442 (26 January 2022).

Co-existence of antibiotic resistance and virulence factors in carbapenem resistant Klebsiella pneumoniae clinical isolates from Alexandria, Egypt.

The emergence and spread of carbapenem resistance among Enterobacteriaceae, particularly Klebsiella pneumoniae, constitute a serious threat to public health, since carbapenems are the last line of defense in the treatment of life-threatening infections caused by drug-resistant Enterobacteriaceae. The current study investigated the co-existence of different virulence factors and carbapenemases in carbapenem-resistant Klebsiella pneumoniae clinical isolates from Alexandria, Egypt. Phenotypic characterization of virulence factors indicated that 41.5% of the isolates were strong biofilm producers, while hypermucoviscosity was detected in 14.9% of the isolates. All isolates harbored five or more virulence factor encoding genes. entB, ycfM, mrkD and fimH were detected in all isolates, while only one isolate was negative for ybtS. uge, iutA, rmpA and kpn were detected in 61 (64.8%), 55 (58.5%), 41 (43.6%) and 27 (28.7%) isolates, respectively, while all isolates lacked magA and k2A. Phenotypic detection of carbapenemases was explored by performing CarbaNP and mCIM/eCIM. CarbaNP test showed positive results in 98.9% of the isolates and positive mCIM tests were observed in all isolates, while 68 (72.3%) isolates showed positive eCIM tests. blaNDM was the most prevalent carbapenemase encoding gene (92.5%) followed by the blaOXA-48 (51.1%), while blaKPC was detected in only one (1.06%) isolate. blaVIM, blaIMP and blaGES were not detected in any of the tested isolates. The widespread of carbapenem-resistant Klebsiella pneumoniae represents a major problem in health care settings. A significant association between certain virulence factors and carbapenemase-encoding genes was observed. Antibiotic stewardship programs and infection control policies should be effectively implemented especially in hospitals to limit the spread of such highly virulent pathogens.

Blood Pressure Regulation in Post-COVID POTS: Beyond Sinus Tachycardia.

Postural orthostatic tachycardia syndrome (POTS) is a frequently diagnosed cardiovascular disorder after COVID-19 infection. POTS is characterized by the presence of excessive sinus tachycardia on standing without a fall in blood pressure (BP). We investigated the BP profile using 24-hour ambulatory BP monitoring in patients with new-onset POTS after COVID-19 compared with prepandemic population-based controls. We performed a case-control study in 100 patients (mean age, 40.0±12.9 years; 85% women) with verified post-COVID-19 new-onset POTS diagnosed by a positive head-up tilt testing versus 100 controls from a population-based cohort with a negative active standing test, no history of syncope, POTS, or endocrine disease (mean age, 42.3±14.0 years; 78% women). Twenty-four-hour BP profile was assessed for circadian BP variation including hypotensive systolic BP (SBP) episodes (<80, <90, and <100 mm Hg). Patients with post-COVID-19 POTS had significantly higher nighttime SBP, but not daytime SBP, and more daytime SBP hypotensive episodes compared with controls. Nondipping (34% versus 19%; P<0.001) and reverse dipping patterns (9% versus 0%; P<0.001) were more frequent in post-COVID-19 POTS. In the logistic regression, patients with post-COVID-19 POTS had significantly higher mean 24-hour SBP (odds ratio, 1.08 [95% CI, 1.04-1.11]; P<0.001) and nighttime SBP (odds ratio, 1.07 [95% CI, 1.04-1.10]; P<0.001), independent of age and sex. Patients with post-COVID-19 POTS demonstrate higher mean 24-hour and nighttime SBP and show disruptions of circadian BP rhythm regulation compared with population-based controls, as well as more daytime hypotensive episodes. Future studies are needed to test whether patients with post-COVID-19 POTS may benefit from tailored BP therapy.