Negative Screening Research Articles

Different characteristics but comparable hypertension rates between two MMT “twin” clinics

Background Patients in methadone maintenance treatment (MMT) may develop age-related medical problems. Objective: To compare hypertension prevalence and its risk factors between two MMT clinics, having similar treatment guidelines, but different characteristics, one from Tel Aviv (TA) and one from Las Vegas (LV). Methods Prevalence of hypertension (systolic ≥140 and or diastolic ≥90 mmHg BP) among all current 291 MMT patients in TA and 180 patients in LV were studied, including body mass index (BMI), drugs in urine, sociodemographic, and addiction history data. Results Hypertension prevalence was comparable in TA (35.4%) and LV (34.4%), however TA patients were older (55.9 ± 9.5 vs. 45.5 ± 13.3, p < 0.001), with fewer females (22 vs. 42.2%, p < 0.001), fewer obese (BMI ≥30) (24 vs. 40.9%, p < 0.001), higher cocaine (21 vs. 7.8%, p < 0.001), and lower cannabis (14.1 vs. 32.4%, p < 0.001) and amphetamines (0 vs. 33.5%) users. Logistic regression found higher BMI to characterize hypertension in both clinics, but in TA also negative urine cocaine, benzodiazepine, and opioids screen, while in LV older age (≥50 y), male gender, and negative urine cannabis screen. Conclusions While TA was characterized with older patients, LV patients had a comparable hypertension rate, as obesity was more prevalent. No drug use was accompanied by higher BMI in TA and therefore associated with hypertension. Weight reduction, hypertension detection and treatment are recommended.

Navigating the Pitfalls of Lung Cancer Screening: A Case Study on the Risks and Costs of Negative Screenings

Navigating the Pitfalls of Lung Cancer Screening: A Case Study on the Risks and Costs of Negative Screenings

Abstract PO2-28-09: Long-term Breast Cancer Risk Prediction in Black Women: External Validation of a Mammography-driven AI Model

Abstract Despite the demonstrated potential of artificial intelligence (AI) in breast cancer risk assessment for personalizing screening recommendations, further validation is required regarding AI model bias and generalizability. We performed external validation in Black women of a mammography-driven AI breast cancer risk model (Mirai) originally developed on screening cohorts primarily consisting of White women. In this institutional review board-approved, Health Insurance Portability and Protection Act (HIPAA)-compliant study under a waiver of consent, we retrospectively analyzed a case–cohort sample nested within the core academic breast cancer screening practice of BJC Healthcare, the hospital partner of Washington University in St. Louis. For the purposes of this validation study, relying on 2D digital mammography (DM) images, we focused on Black women presenting for annual DM screening (Selenia or Selenia Dimensions; Hologic) between 2008 and 2018. Eligible breast cancer cases were derived from all women with a breast cancer diagnosis (with associated biopsy-confirmed tumor pathology via institutional cancer registry) after negative (BI-RADS 1 or 2) DM screening 1 to 5 years prior to cancer diagnosis. We also identified a random sample of controls, defined as women who had negative (BI-RADS 1 or 2) DM screening, with 1 to 5 years of screening follow-up without a cancer diagnosis. Risk scores for all DM exams were calculated via the Mirai model. Performance was evaluated using concordance-index (C) analyses and associated 95% confidence intervals (CIs) for the entire cohort, as well as for study subgroups of invasive versus in-situ cancer and cancer molecular subtypes. We analyzed 1368 DM screening exams, including 672 DM exams from 391 women diagnosed with breast cancer (mean age, 58 years; standard deviation, 10 years) and 696 DM exams from 406 controls (mean age, 55 years; standard deviation, 10 years). The overall C-index was 0.62 [95% CIs 0.60–0.64] for all Black women, which was lower compared to previously reported validation results for Mirai in studies of similar design on predominantly White and racially diverse screening cohorts (C-index = 0.67-0.78). There was no evidence of a significant difference between invasive and in-situ cancer (C-index = 0.64 [95% CIs 0.61–0.66] vs. 0.64 [95% CIs 0.61–0.67]). Compared to other cancer molecular subtypes, performance was significantly higher among triple-negative (C-index = 0.67 [95% CIs 0.62–0.71]) and estrogen receptor (ER) negative cancer (C-index = 0.66 [95% CIs 0.61–0.70]). A previously developed mammography-driven AI model showed overall good performance in long-term breast cancer risk assessment in a dataset of Black women only, particularly for triple-negative and ER- cancer types. However, performance was lower compared to previously reported validation results from similar studies on predominantly White and racially diverse screening cohorts. Our results suggest that further refinements are needed towards more accurate breast cancer risk assessment in Black women. Long-term breast cancer risk prediction performance (C-indices) of Mirai in the full cohort of Black women and in study subgroups. Citation Format: Juanita Hernandez Lopez, Zhixin Sun, Shirin Shoushtari, Ulugbek Kamilov, Debbie Bennett, Aimilia Gastounioti. Long-term Breast Cancer Risk Prediction in Black Women: External Validation of a Mammography-driven AI Model [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-28-09.

Abstract PO3-09-08: Using Social Determinants of Health to Improve Surgical Delays for Breast Cancer Patients at Rush University Cancer Center

Abstract Introduction Delays to surgery in the treatment of breast cancer can lead to worse disease specific mortality and overall survival. Previous work has shown a woman’s time to surgical treatment is influenced by income, which may be secondary to social determinants of health (SDOH) including health literacy, safety, stress, access to health care and transportation, housing, and ability to pay utilities. This study sought to evaluate a screening process for SDOH to assess and address barriers to care for women newly diagnosed with breast cancer. Methods A SDOH screening tool consisting of 7 yes/no questions was developed and used by trained breast oncology nurses via phone call made to all new patients prior to their first visit. Based on patient response, patients are provided with community resources or referred to the hospital social work team. Primary outcome included the SDOH screening results, and secondary outcome included time to surgery. Results 118 patients were screened, of which 60 patients had surgery as their first treatment and were included in this analysis. Twenty-seven patients screened positive for SDOH need. Ten patients reported &amp;gt;3 SDOH concerns and were referred to social work. The most common concerns were food insecurity and trouble paying utilities. Of the 27 patients who screened positively, 18 identified as Black or African American, 3 were Hispanic, 1 Asian and 5 White. The mean household income for these patients based on their reported zip codes was $55,615.78. Average time to surgery for patients with a positive SDOH screen was 37.7 days and negative SDOH screen was 42 days. For patients with a positive SDOH screen, those with 2 or fewer SDOH needs had an average time to surgery of 41.9 days and those with 3 or more SDOH needs had an average 30.6 days until surgery. Discussion Patients who screened positive for SDOH need and were provided resources had a faster time to surgery than patients who initially screened negative for SDOH. Patients referred to social work had the fastest time to surgery. Early identification of SDOH is necessary for all patients to improve equity and outcomes in breast cancer treatment. Citation Format: Hilary Tingley, Madeline McIntosh, McKenzie Klee, Margaret Gladman, Alison Coogan, Andrea Madrigrano. Using Social Determinants of Health to Improve Surgical Delays for Breast Cancer Patients at Rush University Cancer Center [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-09-08.

Abstract PS07-03: Randomized trials of oestrogen-alone and breast cancer incidence: a meta-analysis

Abstract Background Findings from cohort studies compared with those from the Women's Health initiative (WHI) randomized, placebo-controlled clinical trial regarding estrogen-alone and breast cancer risk are discordant. The WHI randomized trial enrolled 10,729 postmenopausal women with prior hysterectomy, mean age 64 years (33.2% 50-59), no prior breast cancer and a non-suspicious baseline mammogram. After 7.2 years intervention and 16.2 years cumulative follow-up, conjugated equine estrogen (CEE)-alone (vs placebo) significantly reduced breast cancer incidence by 22% (P = 0.005) and significantly reduced breast cancer mortality by 40% (P = 0.04) (Chlebowski JAMA 2020). In contrast, cohort studies had opposite findings, estrogen-alone use was associated with significantly higher breast cancer incidence and significantly higher breast cancer mortality. Therefore, we identified all available estrogen-alone randomized clinical trials where breast cancer findings were reported to conduct a meta-analysis examining the totality of the randomized clinical trial evidence regarding estrogen-alone influence on breast cancer incidence. Methods We conducted PubMed and Google Scholar searches on randomized trials and: estrogen, hormone therapy, and breast cancer, and searches from a prior meta-analyses and reviews. In the current meta-analysis, for trials with published relative risks (RR) and 95% confidence intervals (CI), each log-RR was multiplied by weight = 1/V, where V = variance of the log-RR, and V was derived from the corresponding 95% CI. For smaller trials with only breast cancer numbers, a different method was used, the corresponding log-RR = (O – E)/weight, where O is the observed case number in the oestrogen-alone group and E the corresponding expected case number, E = nP. Findings Ten randomized trials, incorporating WHI findings, and findings from nine smaller trials included 14,272 randomized participants and 591 incident breast cancers. Of 9 smaller trials, 6 required negative baseline screening mammograms; mean entry age: 50 to 56 years in 5 trials and 62 to 71 years in 4 trials. In the nine smaller trials, 1.2% (24 of 2029) vs 2.2% (33 of 1514) randomized to estrogen-alone vs placebo (open label, one trial) were diagnosed with breast cancer, respectively (RR 0.65 95% CI 0.38-1.11, P = 0.12). For 5 trials evaluating estradiol formulations, RR = 0.63 95% CI 0.34-1.16, P = 0.15. In the WHI trial, 4.5% (238 of 5310) vs 5.5% (296 of 5429) randomized to estrogen-alone were diagnosed with breast cancer, respectively (RR 0.78 95% CI 0.65-0.93, P = 0.005)). Combining smaller trials and WHI results, 3.6% (262 of 7339) vs 4.7% (329 of 6943) randomized to estrogen-alone vs placebo were diagnosed with breast cancer, respectively (overall RR 0.77 95% CI 0.65-0.91, P = 0.002). Results from a sensitivity analysis for the smaller trials using exact conditional logistic regression were essentially unchanged (RR 0.64 95% CI 0.35-1.13). Interpretation The totality of randomized clinical trial evidence supports a conclusion that estrogen-alone use, among postmenopausal women with prior hysterectomy, significantly reduces breast cancer incidence. This consistent pattern seen in these randomized trials suggests the WHI CEE-alone findings are not “stand alone” outcomes or due to chance. Citation Format: Rowan Chlebowski, Aaron Aragaki, Kathay Pan, Joanne Mortimer, Karen Johnson, Jean Wactawski-Wende, Meryl LeBoff, Sayeh Lavasani, Dorothy Lane, Rebecca Nelson, JoAnn Manson. Randomized trials of oestrogen-alone and breast cancer incidence: a meta-analysis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS07-03.

Patient Characteristics Impact Performance of AI Algorithm in Interpreting Negative Screening Digital Breast Tomosynthesis Studies.

Background Artificial intelligence (AI) is increasingly used to manage radiologists' workloads. The impact of patient characteristics on AI performance has not been well studied. Purpose To understand the impact of patient characteristics (race and ethnicity, age, and breast density) on the performance of an AI algorithm interpreting negative screening digital breast tomosynthesis (DBT) examinations. Materials and Methods This retrospective cohort study identified negative screening DBT examinations from an academic institution from January 1, 2016, to December 31, 2019. All examinations had 2 years of follow-up without a diagnosis of atypia or breast malignancy and were therefore considered true negatives. A subset of unique patients was randomly selected to provide a broad distribution of race and ethnicity. DBT studies in this final cohort were interpreted by a U.S. Food and Drug Administration-approved AI algorithm, which generated case scores (malignancy certainty) and risk scores (1-year subsequent malignancy risk) for each mammogram. Positive examinations were classified based on vendor-provided thresholds for both scores. Multivariable logistic regression was used to understand relationships between the scores and patient characteristics. Results A total of 4855 patients (median age, 54 years [IQR, 46-63 years]) were included: 27% (1316 of 4855) White, 26% (1261 of 4855) Black, 28% (1351 of 4855) Asian, and 19% (927 of 4855) Hispanic patients. False-positive case scores were significantly more likely in Black patients (odds ratio [OR] = 1.5 [95% CI: 1.2, 1.8]) and less likely in Asian patients (OR = 0.7 [95% CI: 0.5, 0.9]) compared with White patients, and more likely in older patients (71-80 years; OR = 1.9 [95% CI: 1.5, 2.5]) and less likely in younger patients (41-50 years; OR = 0.6 [95% CI: 0.5, 0.7]) compared with patients aged 51-60 years. False-positive risk scores were more likely in Black patients (OR = 1.5 [95% CI: 1.0, 2.0]), patients aged 61-70 years (OR = 3.5 [95% CI: 2.4, 5.1]), and patients with extremely dense breasts (OR = 2.8 [95% CI: 1.3, 5.8]) compared with White patients, patients aged 51-60 years, and patients with fatty density breasts, respectively. Conclusion Patient characteristics influenced the case and risk scores of a Food and Drug Administration-approved AI algorithm analyzing negative screening DBT examinations. © RSNA, 2024.

Proarrhythmic drugs, drug levels, and polypharmacy in victims of sudden arrhythmic death syndrome: An autopsy-based study from Denmark

BackgroundSudden arrhythmic death syndrome (SADS), characterized by an unknown or inconclusive cause of death at autopsy together with a negative or nonlethal toxicology screening result, is the most common cause of sudden cardiac death in victims younger than 35 years. The complete causality of SADS remains unclear, with drugs being a potential risk factor. ObjectiveThis study aimed to describe the toxicologic profiles of SADS victims, focusing on proarrhythmic drugs, drug levels, and polypharmacy. MethodsAll deaths in Denmark of those aged 1–35 years in 2000–2019 and 36–49 years in 2007–2019 were examined through death certificates, national registries, and autopsy reports with toxicology screenings. We investigated all sudden unexpected death victims with an autopsy performed, including negative or nonlethal drug findings, where cause of death was unknown or inconclusive (SADS). ResultsWe identified 477 SADS victims; 313 (66%) had a positive toxicology screening result (adjudicated nonlethal), with an average of 2.8 drugs per case. More than half of the SADS victims with a positive toxicology screening result had QT-prolonging or brugadogenic drugs present. Polypharmacy was present in 66%, psychotropic polypharmacy in 37%, and QT-prolonging polypharmacy in 22%, with the most frequent overall and QT-prolonging drug combination being an antipsychotic and a psychoanaleptic drug. QT-prolonging drugs were more often present at suprapharmacologic levels than non–QT-prolonging drugs. ConclusionThe majority of the SADS population had a positive toxicology screening result, with a notably large proportion having proarrhythmic drugs and polypharmacy. This highlights the need for future focus on drugs as a risk factor for SADS.

Negative screening colonoscopy and long-term colorectal cancer risk—is it time to extend the screening interval?

Negative screening colonoscopy and long-term colorectal cancer risk—is it time to extend the screening interval?

Cancer detection rate of breast-MR in supplemental screening after negative mammography in women with dense breasts. Preliminary results of the MA-DETECT-Study after 200 participants

BACKGROUNDDue to increased cancer detection rates (CDR), breast MR (breast MRI) can reduce underdiagnosis of breast cancer compared to conventional imaging techniques, particularly in women with dense breasts. The purpose of this study is to report the additional breast cancer yield by breast MRI in women with dense breasts after receiving a negative screening mammogram. METHODSFor this study we invited consecutive participants of the national German breast cancer Screening program with breast density categories ACR C & D and a negative mammogram to undergo additional screening by breast MRI. Endpoints were CDR and recall rates. This study reports interim results in the first 200 patients. At a power of 80% and considering an alpha error of 5%, this preliminary population size is sufficient to demonstrate a 4/1000 improvement in CDR. RESULTSIn 200 screening participants, 8 women (40/1000, 17.4–77.3/1000) were recalled due to positive breast MRI findings. Image-guided biopsy revealed 5 cancers in 4 patients (one bilateral), comprising four invasive cancers and one case of DCIS. 3 patients revealed 4 invasive cancers presenting with ACR C breast density and one patient non-calcifying DCIS in a woman with ACR D breast density, resulting in a CDR of 20/1000 (95%-CI 5.5–50.4/1000) and a PPV of 50% (95%-CI 15.7–84.3%). CONCLUSIONOur initial results demonstrate that supplemental screening using breast MRI in women with heterogeneously dense and very dense breasts yields an additional cancer detection rate in line with a prior randomized trial on breast MRI screening of women with extremely dense breasts. These findings are highly important as the population investigated constitutes a much higher proportion of women and yielded cancers particularly in women with heterogeneously dense breasts.

Renal artery occlusion in a young woman - a tale of mysterious thrombosis.

Renal artery thrombosis is rare and limited reports exist in the young population. The most common aetiology is thromboembolic disease or abdominal trauma in this population and isolated occurrences are extremely rare. We present the case of an 18-year-old woman with spontaneous unilateral renal artery thrombosis and infarction for whom reperfusion was achieved through endovascular intervention. The aetiology of her thrombosis remains unclear and is under investigation with differential diagnoses being fibromuscular dysplasia, large and medium vessel vasculitis, and thromboembolic causes. To demonstrate the value in attempting salvage of an ischaemic kidney in a young patient with an unexplained spontaneous renal thrombosis. JM is an 18-year-old woman who presented to a large regional tertiary hospital with 3days of right flank pain. She had no infective symptoms and no urinary or bowel changes before admission. She was not pregnant, and her only medication was the oral contraceptive pill commenced 3months prior. A CT angiogram demonstrated right renal artery thrombosis with renal infarction. The kidney was deemed potentially salvageable, and ultrasound defined adequate vessel calibre to access for thrombectomy in the context of a negative coagulopathy screen. The patient underwent thrombolysis, thrombectomy and balloon angioplasty. Intraoperatively, a thin segment of distal stenosis was identified, and angiogram reperfusion was achieved with subsequent improvement in renal function. Renal artery thrombosis in young people is extremely rare and presents a diagnostic and management challenge requiring input from multiple teams including nephrology, rheumatology, paediatrics and vascular surgery. Systemic coagulopathy and vasculitis are differentials against anatomical aetiologies such as fibromuscular dysplasia. Our case adds to the limited literature regarding this in the young population. Renal artery thrombosis with occlusion in young people is very rare and is most often associated with a systemic coagulopathic disorder, such as antiphospholipid syndrome or structural pathology of the renal vasculature such as fibromuscular dysplasia. The work-up of a young female presenting with renal artery thrombosis without any previous medical history screens for a wide range of pathological processes.

P031 An case of cryofibrinogen associated necrotising cutaneous vasculitis on background of aortitis

Abstract Background/Aims Cryofibrinogen is an abnormal protein that forms precipitate in plasma but not in serum. Cryofibrinogenaemia can be detected in healthy individuals and patients with autoimmune diseases, cancer, and infections. Current data suggest that isolated cryofibrinogenaemia can be detected in up to 3% of healthy individuals and it is usually asymptomatic. However, cryofibrinogenaemia can be associated with systemic inflammatory manifestations, of which cutaneous involvement is the most prominent. Methods A 76-year-old male patient presented with acute and progressive necrotising ulcers in the lower limbs along with high inflammatory markers and general decline. He had a background of large vessel vasculitis (aortitis), which was diagnosed with a PET-CT scan three years prior to the current presentation. He was previously treated with oral steroids and eight cycles of cyclophosphamide demonstrating an excellent response with complete resolution of the aortitis on the follow-up PET-CT scan. The patient had remained on maintenance treatment with azathioprine (3mg/kg) as well as therapeutic anticoagulation for atrial fibirillation. Results After thorough investigations for an infective cause and poor response to broad spectrum antibiotics, he was reviewed further for recurrence of large vessel vasculitis. A CT angiogram showed concentric symmetrical soft tissue thickening surrounding the thighs and lower limb arteries without luminal stenosis, suggestive of periarterial inflammation. A further MR angiogram of the aorta did not confirm any evidence of aortic, iliac or visceral artery stenosis. A CT chest/abdomen/pelvis excluded any other pathology or malignancy. Additional investigations showed negative ANA and ENA screen, rheumatoid factor, antiphospholipid antibodies, cryoglobulins, hepatitis virus screen, whilst complement and immunoglobulin levels were normal. However, cryofibrinogen was reported positive and a diagnosis of cryofibrinogen-associated necrotising cutaneous vasculitis was concluded. The patent was started on IV cyclophosphamide (15mg/kg) along with IV methylprednisolone (250mg for the first 3 doses) along with each pulse therapy. After the first two pulses, the patient had a favourable clinical and serological response to the immunosuppressive treatment with improvement in cutaneous lesions and significant reduction in the inflammatory markers. He subsequently underwent an angioplasty for tightly stenotic/occluded tibioperoneal trunk with good recanalisation. Conclusion This is a rare overlap syndrome of new-onset small vessel necrotising cutaneous vasculitis on previous background of large vessel disease (aortitis). In most severe cases with essential cryofibrinogenaemia, the mainstay treatment is with corticosteroids and other immunosuppressive agents in combination with oral anticoagulants and/or low-dose aspirin. Post treatment, the risk of relapse remains high and immunosuppressive therapy may only have a limited impact on the course of thrombotic vasculopathy in the absence of inflammation. More research and longitudinal data are required to optimise treatment protocols and outcomes in patients with cryofibrinogen-associated systemic vasculitis. Disclosure A. Psarras: None. J. David: None. R. Luqmani: None. S. Dubey: Consultancies; Boehringer Ingelheim. Member of speakers’ bureau; Janssen.

P181 Clinical assessment of radiologically defined clinically isolated aortitis in a single centre study

Abstract Background/Aims Aortitis may occur in the absence of systemic vasculitis and is termed clinically isolated aortitis (CIA). Our purpose was to describe a cohort of patients with CIA and compare their characteristics with aortitis patients associated with rheumatic diseases. Methods We conducted a retrospective analysis of 32 patients with non-infectious aortitis evaluated in our centre. Online records were analysed. We included demographic variables, symptoms, laboratory data, imaging, treatment, outcomes, and mortality. The description of quantitative variables was made using percentages and medians with interquartile range (IQR). Results Out of 32 patients, 10 were classified as CIA and 22 had other inflammatory diseases (approx. 1:2 ratio) - fourteen had giant cell arteritis, 4 had Takayasu's arteritis, 2 with granulomatosis with polyangiitis, 1 each with IgG4 related disease and ankylosing spondylitis, classified according to the ACR/EULAR criteria for each disease. All patients underwent PET-CT imaging confirming isolated aortitis; none had an artery biopsy. Table 1 shows the main clinical characteristics. Among the CIA patients, the median duration of follow-up was 65 months (IQR 42-72). Three patients were asymptomatic and seven had constitutional symptoms (fever, weight loss, sweats, fatigue). Only one patient reported abdominal, back pain. The diagnosis was incidental in two cases. All patients had negative infection screen and serological markers for other rheumatologic conditions. Six (60%) patients had involvement only of the abdominal aorta, 2 had only thoracic aorta, and 2 had abdominal and thoracic aortitis. Six patients (60%) were treated with glucocorticoids (GCs) and methotrexate, 2 with GCs alone, 1 with GCs and mycophenolate mofetil, and 1 patient had resistant disease requiring tocilizumab. Four patients had follow-up PET-CT imaging: 2 showed reduction in FDG avidity, 1 had a stable tracer uptake, and 1 had no evidence of persistent aortitis. All the CIA patients demonstrated clinical and biochemical (ESR/CRP) improvement and at follow-up. Conclusion Our CIA patients had a male predominance, between the sixth and seventh decades, consistent with the previous literature. Aneurysms are more common in CIA patients than in those with GCA or TAK. There is no fixed protocol for CIA but conventional DMARDs and glucocorticoids are helpful. Disclosure S. Jain: None. M. Muñoz-Urbano: None. A. Khormi: None. S. Sangle: Other; Principle Investigator for HAVEN Trial. D. D'Cruz: Consultancies; GlaxoSmithKline, CSL Vifor. Grants/research support; Medical Research Council, National Institute for Health and Care Research. Other; Principal Investigator Clinical trials with Pfizer. Eli Lilly, AbbVie, Syneos, Idorsia.

Clusters of Compact Intracloud Discharges (CIDs) in Overshooting Convective Surges

AbstractWe observed five clusters of upper‐level compact intracloud discharges (CIDs) moving positive charge up over land and over water in Florida. The clusters each contained 3 to 6 CIDs, and the overall cluster duration ranged from 27 to 58 s. On average, the CIDs in a given cluster occurred 11 s apart and were separated by a 3D distance of about 1.5 km. All the clustered CIDs were located above the tropopause and were likely associated with convective surges that penetrated the stratosphere. The average periodicity of CID occurrence within a cluster (every 11 s) was comparable to the periodicity at which the average cluster area is expected to be bombarded by ≥1016 eV cosmic‐ray particles (every 5 s). Each of such energetic particles gives rise to a cosmic ray shower (CRS) and, in the presence of sufficiently strong electric field over a sufficiently large distance, to a relativistic runaway electron avalanche (RREA). We infer that each of our upper‐level CIDs is likely to be caused by a CRS‐RREA traversing, at nearly the speed of light, the electrified overshooting convective surge and triggering, within a few microseconds, a multitude of streamer flashes along its path, over a distance of the order of hundreds of meters (as per the mechanism recently proposed for lightning initiation by Kostinskiy et al., 2020, https://doi.org/10.1029/2020JD033191). The upper‐level CID clustering was likely made possible by the recurring action of energetic cosmic rays and the rapid recovery of the negative screening charge layer at stratospheric altitudes.

Significance of colonization by antibiotic-resistant organisms prior to congenital heart disease surgery in children from low- to middle-income countries sent by non-governmental organizations to Switzerland.

Children with congenital heart disease (CHD) from low- to middle-income countries (LMIC) are suspected to have a high prevalence of antibiotic-resistant microorganisms (ARMOs) carriage, but data are currently lacking. Carriage of ARMOs could impact the post-operative course in pediatric intensive care unit (PICU). The aim of the study was to assess the prevalence of ARMOs carriage in children with CHD from LMIC and its impact on post-operative outcomes. This was a retrospective monocentric study from 01/2019 to 12/2022. Included patients were children (0-18 years) from a LMIC admitted after CHD surgery and with AMRO screening performed the week before. Infections and post-operative evolution were compared based on ARMOs carriage status. Among 224 surgeries (median age 38.5 months (IQR 22-85.5)), ARMOs carriage was evidenced in 95 cases (42.4%). Main organisms isolated were Extended Spectrum Beta-Lactamase (ESBL) producing E. coli (75/224) 33.5%)) and ESBL-K. pneumoniae (30/224) 13.4%)). Median mechanical ventilation duration was 1 day (IQR 0-1), PICU stay 3 days (IQR 2-4) and hospital stay 6.5 days (IQR 5-10). A total of 17 infectious episodes occurred in 15 patients, mostly consisting in hospital-acquired pneumonia (HAP) (12/17). Only two infections were caused by a colonizing ARMO. Occurrence of infections and patients' outcome were similar between ARMO carriers and non-carriers. Higher use of carbapenems (6 (6.3%) vs 1 (0.8%), p = 0.04) and a trend to a higher use of vancomycin (14 (13.7%) vs 9 (6.9%), p = 0.04) in case of ARMOs carriage. Applying current guidelines, negative swab screening could have led to sparing most of empirical vancomycin therapy (11/12) for HAP based on current guidelines. Prevalence of AMROs carriage is high in children from LMIC and has a limited impact on patients' outcome. However, ARMOs carriage leads to higher consumption of antibiotics. Screening may help saving use of broad-spectrum antibiotic in non-carrier patients.

Timely Completion of Direct Access Colonoscopy Is Noninferior to Office Scheduled for Screening and Surveillance.

We aimed to evaluate whether direct access colonoscopy (DAC) is noninferior to office-scheduled colonoscopy (OSC) for achieving successful colonoscopy. DAC may improve access to colonoscopy. We developed an algorithm assessing eligibility, risk for inadequate preparation, and need for nursing/navigator assistance. This was a retrospective, single-center study of DAC and OSC patients from June 5, 2018, to July 31, 2019. Patients were 45 to 75 years old with an indication of screening or surveillance. A successful colonoscopy met 3 criteria: complete colonoscopy (cecum, anastomosis, or ileum), adequate preparation (Boston Score ≥2/segment), and performed <90 days from initial patient contact. Unsuccessful colonoscopy did not meet ≥1 criteria. Secondary end points included days to successful colonoscopy, preparation quality, polyp detection, and 10-year recall rate. Noninferiority against risk ratio value of 0.85 was tested using 1-sided alpha of 0.05. A total of 1823 DAC and 828 OSC patients were eligible. DAC patients were younger, with a greater proportion of black patients and screening indications. For the outcome of successful colonoscopy, DAC was noninferior to OSC (DAC vs. OSC: 62.7% vs. 57.1%, RR 1.16, 95% LCL 1.09, P=0.001). For DAC, days to colonoscopy were fewer, and likelihood of 10-year recall after negative screening greater. Boston Score and polyp detection were similar for groups. Black patients were less likely to achieve successful colonoscopy; otherwise, groups were similar. For unsuccessful colonoscopies, proportionally more DAC patients canceled or no-showed while more OSC patients scheduled >90 days. DAC remained noninferior to OSC at 180 days. DAC was noninferior to OSC for achieving successful colonoscopy, comparing similarly in quality and efficiency outcomes.

Malnutrition Screening with Nutritional Risk Screening 2002 prior to Assessment as Part of GLIM Criteria in Patients Undergoing Major Abdominal Surgery for Gastrointestinal Cancer

Introduction: For diagnosing malnutrition as an important modifiable risk factor in surgical cancer patients, GLIM criteria offer a standardised diagnostic pathway. Before assessing malnutrition, it is suggested to screen for malnutrition with an implemented screening tool, i.e., the NRS-2002. Validated data regarding the applied screening tool and its relevance for predicting outcome parameters in surgical patients is sparse. Methods: 260 patients undergoing major abdominal surgery for cancer were retrospectively analysed. Between January 2017 and December 2019, patients were prospectively screened for malnutrition with the Nutritional Risk Score 2002 (NRS). Irrespective of their screening result malnutrition was assessed with GLIM criteria using CT scan at lumbar level 3 for measuring skeletal muscle mass (GLIM MMCT). Patients with negative screening results (NRS ≤2) were analysed regarding their malnutrition assessment and outcome parameters. Results: Thirty four of 67 patients with NRS ≤2, posing no risk for malnutrition, were diagnosed malnourished according to GLIM MMCT (n = 34, 50.7%). 19 patients (55.9%) with NRS ≤2 and malnutrition according to GLIM had at least one complication, 12 patients (35.3%) had a severe complication (Clavien-Dindo grade ≥ 3a), in 26.5% re-laparotomy was necessary, readmission within 1 month in 20.6% of patients, and length of hospital stay was 18.76 ± 12.66, which was in total worse in outcome compared to the whole study group (n = 260). Patients with NRS ≤2 but diagnosed malnourished by GLIM were at significant higher risk to develop a severe complication (OR 2.256, 95% CI: 1.038–4.9095, p = 0.036) compared to patients with NRS ≤2 but not being diagnosed malnourished. The risk for overall complications was significantly increased in patients with malnutrition diagnosed by the GLIM criteria using MMCT (OR 2.028, 95% CI: 1.188–3.463, p = 0.009). Patients screened at risk with NRS ≥3 and diagnosed malnourished by GLIM were also at significant higher risk for developing complications (OR 1.728, 95% CI: 1.054–2.832, p = 0.029). Conclusion: GLIM MMCT is suitable for diagnosing malnutrition and estimating postoperative risk in gastrointestinal cancer patients. Nutritional assessment only in patients with NRS >2 may bear the risk to miss malnourished patients with high risk for poor clinical outcome. In every patient undergoing major cancer surgery, regular assessment of nutritional status regardless of screening result should be performed exploiting CT body composition analysis.

Distance to Burn Center Does Not Impact Long-term Anxiety and Depression Risk Following Burn Injury.

Burn injury predisposes patients to significant psychological morbidity, including anxiety, depression, and posttraumatic stress. Adding to the burden of injury, patients often require transfer to specialized burn centers located far from home. We hypothesized that greater distances between a patient's home address and the treating burn center would increase the rate of postinjury anxiety and depression. From January 2021 to June 2023, patients who were admitted to our American Burn Association verified center and seen for posthospitalization follow-up were identified. Demographics, burn characteristics, and follow-up anxiety (Generalized Anxiety Disorder-7) and depression (Patient Health Questionnaire-2) screening scores were reviewed. Comparisons between patients with positive and negative screens were performed using univariate analysis followed by logistic regression. Linear regression was used to evaluate the relationship between distance to the burn center and incremental screening scores. Of the 272 patients identified, 35.6% and 27.9% screened positive for anxiety and depression, respectively. The distance to burn center was not greater among patients with positive screens. Likewise, no statistically significant linear relationship was found between distance to the burn center and incremental screening scores. Morphine milligram equivalents on the last day of hospitalization (P = .04) and a prior psychiatric history (P < .001) all predicted postinjury anxiety. Total body surface area burned (P = .02) and a prior psychiatric history (P = .02) predicted postinjury depression. The distance between a patient's home and the treating burn center does not alter anxiety and depression rates following burn injury, further supporting the transfer of patients to specialized centers.

Reduced emergency department use among insured individuals receiving extended-release buprenorphine in a health system setting

IntroductionExtended-release buprenorphine (XR-Bup) is associated with reduced opioid use and opioid negative urine drug screens. Little is known about its use in outpatient addiction care provided within health systems. MethodsIndividuals prescribed XR-Bup were identified from electronic health records; chart abstraction was conducted. Primary outcome was all-cause emergency department (ED) use. Secondary outcomes included ED use or inpatient stays for mental health or substance use, ED use for any other cause, discontinuation reasons, and drug substitution. Statistical comparisons used nonparametric tests from related samples (McNemar’s test and Wilcoxon matched pair tests) to test outcomes six months prior and 6 months following XR-Bup initiation. Results152 individuals had an XR-Bup order, 126 received >1 injection. Among those consistently insured 6 months prior to and following XR-Bup initiation (n=99), the mean number of injections following initiation was 3.95; one-third received 6 doses in the 6 months. The proportion of individuals using ED services for all causes declined (41% prior vs. 28% following XR-Bup initiation, p<.05); similar results were found for secondary ED use outcomes. The proportion of individuals requiring inpatient treatment for mental health or substance use also declined (46% vs. 16%, p<.01). Common reasons for discontinuing XR-Bup included losing insurance (21%) or cost (11%). The most common non-prescribed substances used during treatment were opioids (n=31) and THC (n=20). ConclusionsIn this non-randomized retrospective observational study, use of XR-Bup was associated with reduced ED use 6 months following initiation. XR-Bup may help health systems reduce use of costly ED services.

Abstract LB405: CTP synthase 1 is a synthetic vulnerability in prostate cancer treated with supraphysiological androgen

Abstract Bipolar androgen therapy (BAT) is the cyclical administration of supraphysiological androgen (SPA), which can be an effective treatment for 30-40% of patients with castration-resistant prostate cancer. We sought to improve the efficacy of BAT by better understanding its molecular consequences in prostate cancer. Given that the androgen receptor (AR) regulates cellular metabolism, we hypothesized that SPA induces dependencies on specific metabolic pathways that might be exploited therapeutically. A negative selection metabolism-focused CRISPR-KO screen in LNCaP cells treated with SPA suggested that the deletion of several enzymes involved in de novo nucleotide synthesis enhances growth suppression by SPA. A top hit was cytidine triphosphate synthase 1 (CTPS1). CTPS1 converts UTP to CTP in the final step of de novo pyrimidine synthesis. Exposure of SPA-treated prostate cancer cell lines to STP-B, a potent and highly selective inhibitor of CTPS1 (PMID 37008165), increased cell death in vitro and in vivo, indicating that CTPS1 constitutes a metabolic vulnerability in this context. Inhibition of CTPS1 with STP-B induced S phase cell cycle arrest and replication stress, as indicated by phosphorylation of RPA and CHEK proteins, which was augmented by treatment with SPA. CTPS1 likely becomes a vulnerability in SPA-treated prostate cancer due to the downregulation of MYC by SPA, which we found leads to a reduced abundance of enzymes required for nucleotide synthesis and nucleotides, particularly CTP. This rewires nucleotide synthesis and salvage pathway such that de novo synthesis of CTP is required to avoid replication stress and cell death. Altogether, this work suggests that inhibition of CTPS1 may enhance the efficacy of BAT through the induction of replication stress. Selective inhibitors of CTPS1 have entered clinical development (NCT05463263), increasing the feasibility of a combination therapy clinical trial design for patients with prostate cancer. Citation Format: Sheila Jonnatan, Rajendra Kumar, Varsha Vakkala, Karthik Vasan, Zachary R. Chalmers, Daniel R. Schmidt, Philip A. Beer, Matthew G. Vander Heiden, Samuel R. Denmeade, Navdeep S. Chandel, Laura A. Sena. CTP synthase 1 is a synthetic vulnerability in prostate cancer treated with supraphysiological androgen [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB405.

Comparison of Aesthetic and Functional Rhinoplasty Outcomes Between Patients with Body Dysmorphic Disorder and Normal Individuals.

Rhinoplasty is among the top five most popular cosmetic surgical procedures worldwide. Among rhinoplasty candidates, the most common mental health disorder is body dysmorphic disorder. (BDD). The present study aimed to assess the prevalence of BDD among rhinoplasty candidates, its association with the patient's self-assessment of aesthetic outcome and nasal functional, post-rhinoplasty compared to applicants with negative screening for BDD. The following study is a cross-sectional, comparative study. Out of the 209 rhinoplasty candidates screened by the BDDQ questionnaire, 39 were positive for BDD. From the remaining 170 patients who screened negative for BDD, 39 participants were randomly selected as the control group for the comparative analysis. Rhinoplasty outcome evaluation (ROE) and standardized cosmesis and health nasal outcomes survey-cosmetic (SCHNOS-C) questionnaires were used for assessment of patient satisfaction with the cosmetic outcome of rhinoplasty. Nasal obstruction symptom evaluation (NOSE) and standardized cosmesis and health nasal outcomes survey-obstruction (SCHNOS-O) were used for the assessment of satisfaction with functional outcomes between groups of patients screened positive and negative for BDD. The prevalence of BDD was 18.66% among rhinoplasty candidates. The average age of patients screened positive for BDD was 31.41. The mean ROE score was significantly lower (i.e. lower satisfaction) in patients screened positive for BDD (15.69 versus 19.08, P = 0.001), regardless of confounding variables, such as age, sex, and marital status. SCHNOS-C score was higher (i.e. less satisfaction) among patients with BDD (47.01 versus 34.96, P = 0.021) and was significantly associated with higher odds of severe aesthetic concern post-rhinoplasty (OR (95%CI) = 5.000 (1.135-22.022), P = 0.033). Patients screened positive for BDD had significantly higher NOSE scores (i.e. less satisfaction with functional outcome) compared to participants negative for BDD (49.74 versus 37.82, P = 0.012). SCHNOS-O score had no significant association with BDD (P = 0.053). Furthermore, there was no significant association between BDD and NOSE or SCHNOS-O score after adjustment for the confounders. Patients screened positive for BDD were significantly less satisfied with the cosmetic outcome of the rhinoplasty compared to those screened negative for BDD. Assessment of BDD among rhinoplasty candidates before surgery, could potentially be beneficial for both patients and surgeons. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .