Impact In Clinical Management Research Articles

Youth-onset Type 2 Diabetes: An Overview of Pathophysiology, Prognosis, Prevention and Management.

This review explores the emerging evidence regarding pathogenesis, future trajectories, treatment options, and phenotypes of youth-onset type 2 diabetes (T2D). Youth-onset T2D is increasing in incidence and prevalence worldwide, disproportionately affecting First Nations communities, socioeconomically disadvantaged youth, and people of colour. Youth-onset T2D differs in pathogenesis to later-onset T2D and progresses more rapidly. It is associated with more complications, and these occur earlier. While there are limited licensed treatment options available, the available medications also appear to have a poorer response in youth with T2D. Multiple interacting factors likely contribute to this rising prevalence, as well as the increased severity of the condition, including structural inequities, increasing obesity and sedentary lifestyles, and intergenerational transmission from in-utero exposure to maternal hyperglycemia and obesity. Youth-onset T2D is also associated with stigma and poorer mental health, and these impact clinical management. There is an urgent need to develop effective interventions to prevent youth-onset T2D and enhance engagement of affected youth. It is also critical to better understand the differing phenotypes of youth-onset T2D, to effectively target treatments, and to address intergenerational transmission in high-risk populations.

Access for adolescents and young adults with hard-to-cure cancer to PROFYLE: The pan-Canadian precision oncology pipeline.

10012 Background: Cancer is the most common cause of disease-related death in children, adolescents and young adults (CAYA). Approximately, 1.5% of patients with cancer in Canada are adolescents and young adults (AYAs) (age 15-29). AYAs often present with advanced disease and limited access to clinical trials including genomic testing. The PRecision Oncology For Young peopLE (PROFYLE) national, collaborative program, was created to provide equitable access to molecular profiling to identify novel targeted treatment options for CAYA with hard-to-cure cancers. The AYA node of PROFYLE aims to enhance the inclusion of AYAs across Canada at pediatric and adult centers while raising awareness of improving cancer outcomes of this underserved population. Methods: Building upon 3 pre-existing regional precision oncology programs, PROFYLE was implemented as the first pan-Canadian precision oncology pipeline. The PROFYLE study is multi-centred, non-randomized, interventional, and qualitative. Inclusion criteria: ≤29y; treatment at a Canadian center; diagnosis of a hard-to-cure cancer. It includes genomic and transcriptomic sequencing of paired germline and cancer fresh/frozen samples. Actionable findings, potential targeted therapy options including available clinical trials, clarification of diagnosis, and genetic counseling recommendations are provided to the clinical care team. Results: To date, > 1,200 CAYA are included from all provinces. Of these, 33% were AYAs. Cancer diagnoses included: 47% sarcoma, 15% leukemia/lymphoma, 13% CNS tumor, 25% other. Of the AYAs enrolled, 53% had ≥1 significant tumour profiling finding (48% specific mutations/fusions; 6% DNA repair defect signature, hypermutation, microsatellite instability, chromosomal instability; 3% predictors of therapeutic resistance; 5% outliers in gene expression). 71% had potentially useful findings (15% diagnostic; 9% prognostic; 59% therapeutic; 2% etiologic; 15% cancer predisposition; 2% secondary germline; 0.5% pharmacogenetic). 23% had a pathogenic/likely pathogenic germline variant. 60% had ≥1 potentially actionable somatic alteration. 64% of clinicians indicated that molecular findings impacted clinical management (12% diagnostic; 6% prognostic, 60% therapeutic; 16% germline genetic). 24% indicated a change in treatment planning in response to these findings. Conclusions: The goal of developing a national precision oncology pipeline that provides equitable access to molecular profiling in a clinically relevant timeframe has been realized through the establishment of PROFYLE. Findings demonstrate that the sequencing platform provided medically informative results in the majority of enrolled AYAs. The success of PROFYLE underscores the importance of the continuing efforts to increase the access to this precision oncology initiative for all AYAs with cancer in Canada.

Abstract PO1-09-02: Universal genetic testing for women with newly diagnosed breast cancer identified many mutations, impacted clinical management and caused no psychological distress to patients

Abstract Background: For newly diagnosed breast cancer (BC) patients, identification of pathogenic germline mutations in hereditary breast cancer (HBC) genes can inform clinical management and risk mitigation strategies and identify patients who would benefit from targeted therapy and clinical trials. Offering germline testing based on NCCN or other guidelines fails to identify all patients with germline HBC gene mutations, potentially with adverse consequences for patients and their families. As an integral part of the study, we have explored the acceptance of universal testing among patients and clinicians. Methods: This is the largest Australian multi-centre prospective study exploring the prevalence of hereditary pathogenic variants in the Australian BC population. 650 newly diagnosed consecutive, consented patients with non-metastatic breast cancer or high-grade DCIS were recruited from May 2020 to March 2023 in 2 phases. Phase 1 (n=157) offered a combination of germline and somatic sequencing. Germline testing was performed by whole genome sequencing on DNA from blood or saliva, and the data analyzed for actionable HBC gene mutations, including large genomic rearrangements. Germline variants were interrogated for pathogenic variants in BRCA1, BRCA2, PALB2, ATM, CHEK2, BARD1, BRIP1, RAD51B, RAD51C, RAD51D, MLH1, MSH2, MSH6, PMS2, CDH1, PTEN, STK11, TP53 and NTHL1.Tumour sequencing will be reported separately. Phase 2 (n=493) included germline exome sequencing with no somatic sequencing. The objectives were to assess the additional actionable HBC gene mutations identified by universal testing compared to algorithmic based (MANCHESTER and BOADICEA scores) and NCCN guidelines, the clinical impact of this identification and the prevalence of germline mutations in the general BC population. A 3-generation pedigree was constructed for every patient for accurate estimation of NCCN, MANCHESTER, and BOADICEA scores. Phase 1 patients completed surveys of perceptions of universal testing, psychological distress and cancer-specific worry pre- and post-testing. Results: 50 carriers of actionable germline mutations were identified: (7.7%). BRCA1 (n=10), BRCA2 (n=12), PALB2 (n=7), CHEK2 (n=10), ATM (n=4), PMS2 (n=2), MSH6 (n=1), RAD51C (n=2), and BARD1 (n=3). One carrier had both PALB2 and CHEK2 mutations. Updated NCCN guidelines (2023 version) identified 44/50 pathogenic germline variant carriers (88%). The BOADICEA and MANCHESTER scores only identified 22 carriers (44%). Immediate clinical management changed due to the discovery of HBC gene in 40/50 (80%). Among 105 participants, cancer-specific distress declined from pre- to post-testing. Anxiety, stress and depression did not change. 90/103 participants agreed that genetic testing should be routine, 100/104 reported their decision to undergo testing as correct. All (n=25) BC clinicians reported that genetic test results were helpful for important treatment decisions and none that testing was distressing to patients. Conclusion: HBC gene mutation prevalence was 7.7%. Universal germline HBC gene testing is the best method for detecting carriers. Current testing guidelines would have missed HBC genes which would have impacted clinical management. Updated NCCN guidelines were sensitive in the detection of HBC gene mutation, but more than half of HBC gene mutations were missed by Australian standards. Discovery of HBC gene mutations led to changed management in most cases. Universal testing is highly acceptable to clinicians and patients who reported no adverse impact on psychological distress or cancer-specific worry and no decision regret. Germline mutations identified and their impact on management Citation Format: Dilanka De Silva, Lesley Stafford, Anita Skandarajah, Michelle Sinclair, Lisa Devereux, Kirsten Hogg, Maira Kentwell, Allan Park, luxi Lal, Magnus Zethoven, Madawa Jayawardena, Fiona Chan, Paul James, Geoffrey Lindeman, Ian Campbell, Bruce Mann. Universal genetic testing for women with newly diagnosed breast cancer identified many mutations, impacted clinical management and caused no psychological distress to patients [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 PO1-09-02.

Impact of Slim Linear Echoendoscope on the Practice of EUS.

Standard linear echoendoscopes have a large distal tip and bending radius, which can preclude adequate examination in some patients. We examined the impact of having available slim linear echoendoscopes (SLE) on our endoscopic ultrasound (EUS) practice. As a quality improvement measure, data on the need for the use of SLE were documented in 2000 consecutive procedures performed over a 10-month period from February to November 2022. When examination using a standard size echoendoscope failed due to technical limitations, the procedure was reattempted in the same session using a SLE. The main outcome was the impact of SLE, which was defined as the establishment of a new diagnosis or if findings altered treatment plan. A complete EUS examination failed in 23 of 2000 procedures (1.15%, 95% CI, 0.73-1.72%) performed using standard size echoendoscope (14 male, median age 73y [IQR 66 to 79]). The examination was technically successful when using SLE in 22 of 23 (95.6%) patients. SLE impacted clinical management in all 22 patients (100%) by establishing tissue diagnosis in 19 and/or altering subsequent treatment plan in 5. Adverse event of transient hypoxia was observed in one patient (4.3%). A very experienced EUS team required SLE in 1.1% of consecutive examinations. Our findings suggest that when used, 95% of patients benefitted as it had a significant impact on their clinical management.

Gestational trophoblastic neoplasia: does centralization of care impact clinical management?

ObjectiveInternational societies advocate for gestational trophoblastic neoplasia referral to designated expert centers. This study assessed the impact of centralization of trophoblastic care on clinical outcomes.MethodsA centralized program was implemented in...

Gestational trophoblastic neoplasia (GTN): Does centralization of care impact clinical management? (2206)

Gestational trophoblastic neoplasia (GTN): Does centralization of care impact clinical management? (2206)

Urine Cytology Rarely Escalates Clinical Management in the Surveillance of Non-muscle-Invasive Bladder Cancer.

The use of urine cytology in the surveillance of non-muscle invasive bladder cancer (NMIBC) is widely variable in clinical practice. We studied the impact of surveillance urine cytology on clinical decision making during NMIBC surveillance. A retrospective chart review was conducted on patients surveilled for clinical NMIBC from 2013 to 2020 with at least one follow-up cytology result after diagnosis. Patients were classified into risk categories according to American Urological Association (AUA) NMIBC guidelines. Data were obtained regarding tumor recurrence pathology and the frequency and findings of surveillance cystoscopies and urine cytologies. Positive (suspicious, malignant) and negative (atypical or negative for malignant cells) cytology results were correlated with cystoscopy and pathology findings when obtained within 3 months of the cytology specimen to determine if cytology impacted plan of care. Two hundred fourteen patients with NMIBC were followed for a median of 34 months, with 1045 urine cytologies collectively obtained over the surveillance period. There were no positive urine cytologies among patients with low-risk NMIBC; therefore, cytology did not change management in this cohort. The potential for cytology to escalate management for patients of any risk group (ie, positive cytology in the absence of positive cystoscopy or pathology findings) occurred in 30 (2.9%) cases. However, clinical decision making was only altered in 4 cases (0.4% of all cytologies). Less than 1% of urine cytology specimens collected during NMIBC surveillance impacted clinical management, none of whom had low-risk disease. The use of urine cytology for surveillance of low-risk NMIBC should continue to be strongly discouraged, as it did not change management in any such cases.

Impact of wideband cardiac magnetic resonance on diagnosis, decision-making and outcomes in patients with implantable cardioverter defibrillators.

Although myocardial scar assessment using late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging is frequently indicated for patients with implantable cardioverter defibrillators (ICDs), metal artefact can degrade image quality. With the new wideband technique designed to mitigate device related artefact, CMR is increasingly used in this population. However, the common clinical indications for CMR referral and impact on clinical decision-making and prognosis are not well defined. Our study was designed to address these knowledge gaps. One hundred seventy-nine consecutive patients with an ICD (age 59 ± 13 years, 75% male) underwent CMR using cine and wideband pulse sequences for LGE imaging. Electronic medical records were reviewed to determine the reason for CMR referral, whether there was a change in clinical decision-making, and occurrence of major adverse cardiac events (MACEs). Referral indication was the most common evaluation of ventricular tachycardia (VT) substrate (n = 114, 64%), followed by cardiomyopathy (n = 53, 30%). Overall, CMR resulted in a new or changed diagnosis in 64 (36%) patients and impacted clinical management in 51 (28%). The effect on management change was highest in patients presenting with VT. A total of 77 patients (43%) experienced MACE during the follow-up period (median 1.7 years), including 65 in patients with evidence of LGE. Kaplan-Meier analysis showed that ICD patients with LGE had worse outcomes than those without LGE (P = 0.006). The clinical yield from LGE CMR is high and provides management changing and meaningful prognostic information in a significant proportion of patients with ICDs.

Integrating rapid exome sequencing into NICU clinical care after a pilot research study

Genomic sequencing is a powerful diagnostic tool in critically ill infants, but performing exome or genome sequencing (ES/GS) in the context of a research study is different from implementing these tests clinically. We investigated the integration of rapid ES into routine clinical care after a pilot research study in a Level IV Neonatal Intensive Care Unit (NICU). We performed a retrospective cohort analysis of infants admitted with suspected genetic disorders to the NICU from December 1, 2018 to March 31, 2021 and compared results to those obtained from a previous research study cohort (March 1, 2017 to November 30, 2018). Clinical rapid ES was performed in 80/230 infants (35%) with a suspected genetic disorder and identified a genetic diagnosis in 22/80 infants (28%). The majority of diagnoses acutely impacted clinical management (14/22 (64%)). Compared to the previous research study, clinically integrated rapid ES had a significantly lower diagnostic yield and increased time from NICU admission and genetics consult to ES report, but identified four genetic diagnoses that may have been missed by the research study selection criteria. Compared to other genetic tests, rapid ES had similar or higher diagnostic yield and similar or decreased time to result. Overall, rapid ES was utilized in the NICU after the pilot research study, often as the first-tier sequencing test, and could identify the majority of disease-causing variants, shorten the diagnostic odyssey, and impact clinical care. Based on our experience, we have identified strategies to optimize the clinical implementation of rapid ES in the NICU.

Indeterminate skeletal and lymph node lesion on 18F PSMA 1007 PET/CT scanning: lessons from a review at 12 months with PSMA-RADS.

The study utilizes the prostate-specific membrane antigen-reporting and data system (PSMA-RADS) version 1.0 in a real-world patient scenario in the evaluation of equivocal lesions using the PSMA-RADS categorization for patient management and communication in multidisciplinary team (MDT) meetings. A retrospective analysis of 203 patients who had 18F PSMA PET/CT for either restaging or staging over 12 months was undertaken. The scans were evaluated for local disease, lymph node involvement and distant metastases. The scan findings were classified as suspicious for metastases, and equivocal and benign lesions. Experience with PSMA ligand imaging was considered while classifying the lesions, equivocal lesions were assessed with PSMA-RADS and followed up with complementary imaging and/or clinical follow-up assessment or MDT for further patient management. A total of 91 of 203 patients had equivocal lesions. Follow-up assessment was performed in 47 of 91 patients with imaging ( n = 36) or MDT discussion ( n = 11).On follow-up imaging ( n = 36), equivocal lesion was seen in skeletal lesions ( n = 24), pelvic lymph nodes ( n = 6), both skeletal and pelvic nodes ( n = 4), hilar and mediastinal lymph nodes ( n = 1) and spleen ( n = 1). The patients were reclassified as benign, metastatic with few lesion remained equivocal. Overall follow-up assessment impacted clinical management in 47% patients. 18F PSMA PET/CT may show equivocal lesions; many of them in the skeleton, a small proportion of which are ultimately proven metastatic. In contrast, a higher proportion of the equivocal nodes in the pelvis end up being metastatic on follow-up. A structured reporting with PSMA-RADS grading helps in the proper classification of lesions and standardization of reports.

Implementation of a Bedside Point-of-Care Ultrasound Program in a Large Academic Neonatal Intensive Care Unit.

In the adult and pediatric critical care population, point-of-care ultrasound (POCUS) can aid in diagnosis, patient management, and procedural accuracy. For neonatal providers, training in ultrasound and the use of ultrasound for diagnosis and management is increasing, but use in the neonatal intensive care unit (NICU) is still uncommon compared with other critical care fields. Our objective was to describe the process of implementing a POCUS program in a large academic NICU and evaluate the role of ultrasound in neonatal care during early adaption of this program. A POCUS program established in December 2018 included regular bedside scanning, educational sessions, and quality assurance, in collaboration with members of the cardiology, radiology, and pediatric critical care divisions. Core applications were determined, and protocols outlined guidelines for image acquisition. An online database included images and descriptive logs for each ultrasound. A total of 508 bedside ultrasounds (76.8% diagnostic and 23.2% procedural) were performed by 23 providers from December 2018 to December 2020 in five core diagnostic applications: umbilical line visualization, cardiac, lung, abdomen (including bladder), and cranial as well as procedural applications. POCUS guided therapy and influenced clinical management in all applications: umbilical line assessment (26%), cardiac (33%), lung (14%), abdomen (53%), and cranial (43%). With regard to procedural ultrasound, 74% of ultrasound-guided arterial access and 89% of ultrasound-guided lumbar punctures were successful. Implementation of a POCUS program is feasible in a large academic NICU and can benefit from a team approach. Establishing a program in any NICU requires didactic opportunities, a defined scope of practice, and imaging review with quality assurance. Bedside clinician performed ultrasound findings can provide valuable information in the NICU and impact clinical management. · Use of point-of-care ultrasound is increasing in neonatology and has been shown to improve patient care.. · Implementation of a point-of-care ultrasound program requires the definition of scope of practice and can benefit from the support of other critical care and imaging departments and providers.. · Opportunities for point-of-care ultrasound didactics, imaging review, and quality assurance can enhance the utilization of bedside ultrasound..

The value of a negative genetic result when triaging an adnexal mass.

e17553 Background: The baseline risk for ovarian cancer in the general population is 1.2%1. However, women with germline variants in ovarian cancer-associated genes can have a much higher baseline risk for ovarian cancer, up to 54%2. Such a difference in baseline risk presents a triaging challenging for physicians when evaluating adnexal masses. It is well known that identifying pathogenic variants in hereditary cancer syndrome genes often leads to changes in care. Less is known about the utility of negative genetic testing results, specifically in the context of adnexal mass assessment. Methods: An observational, prospective study was designed to examine the clinical impact of multivariate index assay (MIA) and germline genetic testing in patients with a known adnexal mass planned for surgery. Inclusion criteria were: female subjects aged 18-65, presence of an adnexal mass, receiving MIA, and consideration of germline genetic testing. Enrolled physicians selected patients under their care that met inclusion criteria and filled out a short survey describing how the results of each test impacted clinical management. This study was considered IRB-exempt as all information was de-identified. Results: 23 patients were enrolled that received both MIA and germline genetic testing. 21 cases had negative genetic testing and two had positive genetic testing. Both patients with positive genetic testing had low-risk MIA results. Both had risk-reduction surgery with benign findings. Three patients had high-risk MIA results with negative genetic results. All patients had a serial monitoring plan of care. Nine patients with low-risk MIA results and negative genetic results proceeded to surgery. No malignancies were reported. Of the 21 patients with negative genetic results, 17 were not immediately planned for surgery. Conclusions: While not reaching statistical significance, there is a strong association between a negative genetic result and non-immediate surgical intervention. While positive genetic testing results may lead to more aggressive, prophylactic surgical management, negative genetic results may support an expectant management approach. Effectively ruling out the most common hereditary cancer predisposition syndromes may provide physicians with useful insight into a patient's baseline risk. [Table: see text]

The clinical impact of MRI on surgical planning for patients with in-breast tumor recurrence.

The objective of this study was to evaluate the clinical utility of breast MRI for patients with known in-breast tumor recurrence (IBTR). The aim was to determine if the addition of breast MRI altered surgical approach or multidisciplinary management. Previous studies have focused on using breast MRI for surgical planning for index breast cancers (BC) or detecting IBTR. However, the clinical impact of obtaining MRI in the setting of known IBTR has not been evaluated. A single-institution retrospective chart review was performed to compare surgical approach and multidisciplinary management for patients diagnosed with isolated IBTR who did and did not undergo breast MRI following IBTR diagnosis. IBTR was identified in 69 patients, 46% of whom underwent MRI. There was no difference in the operative approach (p = 0.14) for IBTR patients who did and did not undergo breast MRI Additionally, there was no difference in multidisciplinary care, treatment order, metastatic disease identification, or mortality between cohorts. A relatively small subgroup of patients (n = 3) required change in surgical plan based on MRI results. Patients proceeding with surgery first who also underwent breast MRI experienced a significantly longer time to surgical intervention (p = 0.03). Breast MRI following IBTR diagnosis infrequently impacted clinical management, including surgical approach and multidisciplinary care. MRI for local disease assessment at the time of IBTR should be used selectively based on clinical concern.

Molecular Profiling of Well-Differentiated Neuroendocrine Tumours: The Role of ctDNA in Real-World Practice.

Simple SummaryThe analysis of circulating tumour DNA (ctDNA) can help to identify genetic alterations present in cancer cells without the need to access tumour tissue, which can be an invasive approach. This study explored the feasibility of analysing ctDNA in patients with advanced well-differentiated neuroendocrine tumours (WdNETs). A total of 45 patients (15 with WdNETs) were included. Although feasible (with a non-evaluable sample rate of 27.8%), mutation-based ctDNA analysis was of limited clinical utility for patients with advanced WdNETs. While patients with WdNETs could still be offered genomic profiling (if available and reimbursed), it is important to manage patients’ expectations regarding the likelihood of the results impacting their treatment.Background: The role of tumour genomic profiling in the clinical management of well-differentiated neuroendocrine tumours (WdNETs) is unclear. Circulating tumour DNA (ctDNA) may be a useful surrogate for tumour tissue when the latter is insufficient for analysis. Methods: Patients diagnosed with WdNETs underwent ctDNA genomic profiling (FoundationLiquid®); non-WdNETs (paraganglioma, goblet cell or poorly-differentiated neuroendocrine carcinoma) were used for comparison. The aim was to determine the rate of: test failure (primary end-point), “pathological alterations” (PAs) (secondary end-point) and patients for whom ctDNA analysis impacted management (secondary end-point). Results: Forty-five patients were included. A total of 15 patients with WdNETs (18 ctDNA samples) were eligible: 8 females (53.3%), median age 63.2 years (range 23.5–86.8). Primary: small bowel (8; 53.3%), pancreas (5; 33.3%), gastric (1; 6.7%) and unknown primary (1; 6.7%); grade (G)1 (n = 5; 33.3%), G2 (9; 60.0%) and G3 (1; 6.7%); median Ki-67: 5% (range 1–30). A total of 30 patients with non-WdNETs (34 ctDNA samples) were included. Five WdNETs samples (27.78%) failed analysis (vs. 17.65% in non-WdNETs; p-value 0.395). Of the 13 WdNET samples with successful ctDNA analyses, PAs were detected in 6 (46.15%) (vs. 82.14% in non-WdNETs; p-value 0.018). In WdNETs, the PA rate was independent of concomitant administration anti-cancer systemic therapies (2/7; 28.57% vs. 4/6; 66.67%; p-value 0.286) at the time of the ctDNA analysis: four, one and one samples had one, two and three PAs, respectively. These were: CDKN2A mutation (mut) (one sample), CHEK2mut (one), TP53mut (one), FGFR2 amplification (one), IDH2mut (one), CTNNB1mut (one), NF1mut (one) and PALB2mut (one). None were targetable (0%) or impacted clinical management (0%). There was a lower maximum mutant allele frequency (mMAF) in WdNETs (mean 0.33) vs. non-WdNETs (mean 26.99), even though differences did not reach statistical significance (p-value 0.0584). Conclusions: Although feasible, mutation-based ctDNA analysis was of limited clinical utility for patients with advanced WdNETs. The rates of PAs and mMAFs were higher in non-WdNETs. While patients with WdNETs could still be offered genomic profiling (if available and reimbursed), it is important to manage patients’ expectations regarding the likelihood of the results impacting their treatment.

593. Utility of Microbiologic Testing Obtained via Bronchoalveolar Lavage on Asymptomatic Lung Transplant Recipients: A Quality Improvement Study

BackgroundThe utility of surveillance bronchoscopy (SB) in asymptomatic lung transplant recipients (LTR) is controversial. Guidelines regarding the timing of SB and diagnostic testing varies across centers. Studies evaluating the role of microbiologic testing are lacking. Our transplant institute currently performs SB at week 1, and months 1, 3, 6, 9, 12, and 24 post-transplant. We evaluated if routine microbiologic testing obtained during SB impacted clinical management. MethodsThis observational cohort study was performed at Henry Ford Hospital, Detroit, MI and included all LTR done from August 2014 to August 2019. Clinical and laboratory data was abstracted from the electronic medical record Pre/post-SB. Bronchoscopies performed for new or worsening respiratory symptoms, decline in forced expiratory volume at one second ≥10%, new radiographic abnormalities and follow up bronchoscopies to assess stents or recent acute rejection were excluded. Microbiologic tests assessed are shown in Table 2. Management change was defined as reduction in immunosuppression or prescription of antimicrobials. Rate of change in clinical management based on microbiologic test positivity was the primary outcome. Data were analyzed with descriptive statistics. Results449 SB in 107 LTR were evaluated. Median age was 63 years, 68% were male. The average number of SB performed per patient was 4.2 (Table 1). The most common microbiologic tests performed were bacterial (435), mycobacterial (427), and fungal including Pneumocystis jirovecii (1022) (Table 2). The rate of test positivity and resultant change in management are shown in Table 3. The rate of test positivity was highest for bacterial (54%), fungal (27%) and viral tests (6%) with management changes in 12%, 2%, and 3% respectively.Table 1. Patient Demographics Table 2. Rate of Microbiologic Testing per Surveillance Bronchoscopy Table 3. Rate of Microbiologic Positivity and Management Change per Surveillance Bronchoscopy ConclusionThis is the largest study to specifically evaluate the role of routine microbiologic tests during SB in LTR. Bacterial cultures may be appropriate due to higher rates of management changes. However, routine fungal, AFB, and viral studies are unnecessary due to low true positivity, and consequent low rate of management changes. This represents an important opportunity for diagnostic and antimicrobial stewardship.Disclosures All Authors: No reported disclosures

Abstract 12098: A Physics-Based Machine Learning Approach for Instantaneous Classification of Myocardial Infarct Size

Introduction: Intrinsic frequency (IF) method is a novel systems-based approach that uses a single uncalibrated arterial waveform for the analysis of the left ventricle (LV) and arterial function. In a recent Framingham Heart Study, it was shown that IFs derived from carotid waveforms predict incident of heart failure and composite cardiovascular disease events (Hypertension. 2021, 77(2):338-346). The predictive and diagnostic values of IF for acute events such as myocardial infarction (MI) is not fully known. Here, we propose a hybrid IF-machine learning (ML) method to classify the MI size (mass percentage of necrosis over total LV). Methods: We used standard MI rat models (Sprague Dawley; n =27). Necrosis was ensured by occluding proximal left coronary artery for 30 minutes, followed by 3 hours of reperfusion. IFs were computed from carotid waveforms 2 hours after the reperfusion. MI sizes were obtained via histopathology (white areas of LV slices are the necrotic areas in Fig.1). The range of rats’ MI size was from 10.9% to 59.9%. MI sizes of 18% and 36% were considered as the cut-offs for ML classification. A 8-split decision tree was trained as the classifier model using the IFs as predictors. The k -fold cross-validation ( k =3) was used to avoid overfitting. Gini’s diversity index was considered as the split criterion. Results: Our ML model showed accuracies of 86.7%, 85.7%, and 60% for predicting the true class of MI sizes (i.e., large, mid-sized, and small, respectively) (Fig.1). The accuracy was particularly strong (86.7%) for detecting large MI sizes. Conclusions: The results suggest that an IF-based ML model (a physics-based approach) can instantaneously classify the severity of the anatomic infarct size using a single arterial waveform without advanced imaging. Since IFs can be measured noninvasively and remotely (i.e., using a smartphone or wearable devices), our proposed method can have potential clinical impact in management and treatment of patients post MI.

Abstract 12429: What is the Clinical Impact of Echocardiography Among Hospitalized Patients With Prior Testing?

Introduction: The versatility and safety of transthoracic echocardiography (TTE) has made it one of the most frequently ordered cardiac imaging tests. However, for inpatients with prior TTE results, the clinical impact of repeat TTE remains uncertain. Methods: We evaluated the charts of sequential hospitalized patients with prior TTE results who underwent an inpatient TTE. We noted prior and current TTE results, if imaging findings were abnormal [(using definitions from Hua (Echocardiography, 2017)], and if these findings were significantly different between the studies. We then evaluated all records for changes in clinical management, including medication changes, additional diagnostic testing, new specialty consultation, or invasive procedures. We used a multivariable model to determine predictors of changes in clinical management. Results: Of 229 sequential patients who underwent an inpatient TTE [median age 71, 55% male, 90% white, 67% abnormal prior TTE], most met Appropriate Use Criteria (92%), most were abnormal (80%), and most changed in at least one aspect from the prior study (66%). However, despite the majority of repeat TTEs with new changes, clinical management was impacted in only a minority of cases 61 (27%). Of these, 27 (12%) resulted in medication changes; 15 (6%) had further diagnostic testing; 14 (6%) had a new specialty consultation; and 11 (4%) had invasive procedures ordered (cardiac catheterization, pericardial drain placement, and cardiac surgery). After adjusting for ordering provider, race of patient, and study indication, new findings on the TTE predicted changes in clinical management OR 4.2, p<0.001). Conclusion: Despite the large majority of repeat TTE’s meeting AUC guidelines, being abnormal, and having imaging changes, repeat TTE infrequently impacted clinical management. Although new TTE abnormalities are associated with clinical management changes in some cases, the clinical value of repeat TTE in the setting of prior imaging results may be lower than most clinicians assume. Efforts to identify the population for whom TTE studies are most likely to impact clinical care would increase the clinical yield of repeat TTE.

H. pylori Pattern Gastritis with Negative Helicobacter Immunohistochemical Stain: Does A Specific Comment in Pathology Report Impact Clinical Management?

Abstract Introduction/Objective The clinical significance of H. pylori (HP) pattern of gastritis with a negative Helicobacter IHC stain on gastric biopsy is unclear. Some pathologists report this pattern in cases that are highly suggestive of HP infection with a comment raising the possibility of HP infection; however, the subsequent clinical management of these patients has not been well described. Methods/Case Report We conducted a retrospective comparison study of patients with gastric biopsy between 2016 and 2019. Group 1 included patients with chronic active or chronic inactive gastritis and negative HP IHC with a comment stating the gastritis pattern is suggestive of HP. Group 2 included patients with chronic active or chronic inactive gastritis and negative HP IHC with no comment about HP pattern. Results (if a Case Study enter NA) We identified 60 patients in Group 1 which were compared to 63 patients in Group 2. Group 1 more frequently had history of HP (48.3% vs. 29.1%, p<0.05). After diagnosis, Group 1 more frequently received treatment (51.7% vs. 20.6%, p<0.001). Of those who received treatment, Group 1 more frequently received HP treatment (triple or quadruple therapy; 21.7% vs. 1.6%, p<0.001). History of HP did not affect whether a patient was treated (p>0.05). Following post-biopsy HP treatment, more patients in Group 1 received fecal antigen test (23.7% vs. 5.5%, p<0.01). Age, gender, NSAID and PPI use did not differ between groups. Conclusion Adding the diagnostic comment raising the possibility of HP for patients with HP pattern gastritis with negative HP IHC changes clinical management and it is independent of patients’ prior HP history.

Clinical impact on treatment and prognosis of advanced cardiac imaging with echocardiography in the acute setting of a COVID-19 infection

Abstract Background and objectives Despite myocardial injury being related to excess mortality in acute COVID-19 infection, its impact on imaging findings remains unclear. This study aimed to characterize transthoracic echocardiographic (TTE) findings in patients admitted with COVID-19 infections and its impact on management and prognosis. Methods A prospective observational cohort study was performed among 66 COVID-19 patients who were admitted to a tertiary center between March 1 and May 25, 2020 and underwent TTE. High-sensitivity troponin I (hs-cTnI) data, echocardiographic assessment of right and left ventricular (LV) functional parameters, strain, and myocardial work analysis were obtained. Results 2025 patients were admitted with COVID-19 and in 200 a complete TTE study was performed. Due to poor image quality, only 66 studies were included in the final analysis. The median age was 62 years (IQR, 55–70) and 59.1% of patients were males. The most common comorbidity was hypertension (47%), followed by smoking history (30.3%), atrial fibrillation (9.1%), and chronic obstructive pulmonary disease (7.9%). More than half of the patients (39, 59%) were admitted to the ICU, and half of them (33, 50%) required invasive mechanical ventilation. TTE was mainly indicated because of concerns for systemic conditions (50%) and evaluation of hemodynamic assessment (30%). Thirty-six patients (54.5%) had an abnormal TTE result and 57% had elevated hs-cTnI levels. The most common cardiac abnormality was LV diastolic dysfunction in 33% of the patients, followed by right ventricular dysfunction (12%) and LV dysfunction (6%) (Figure 1). LV GLS was reduced in 48.5% of the cases. Myocardial work performance indices were all reduced in patients with an abnormal TTE (GWI 30%, GCW 30%, GWW 40%, and GWE 40%), although differences were not significant (P>0.2 for all parameters). Patients with an abnormal TTE were older and presented a higher cardiovascular risk profile. There were no significant differences in the levels of D-dimer, NTproBNP, and hs-cTnI between patients with and without diastolic dysfunction, RV, or LV dysfunction (P>0.3 for all parameters). Using Spearman rank correlation, there was an inverse relationship between hs-cTnI and LV strain and myocardial work analysis. TTE results impacted clinical management in 60 patients, mainly de-escalation of medical treatment (Figure 2). Abnormal TTE results did not impact in-hospital outcomes. Conclusions Severe echocardiographic abnormalities are uncommon in hospitalized patients with COVID-19 infections, presenting mostly with subclinical myocardial changes, such as diastolic dysfunction, reduced LV GLS, and myocardial work indices, both associated with high-sensitivity troponin I elevation. An echocardiographic study should be limited to rule out long-term ICU complications or to evaluate hemodynamic instability. Although TTE was a valuable tool for guiding management, it had no significant impact on prognosis. Funding Acknowledgement Type of funding sources: None. Figure 1. Findings on TTE studies.Figure 2. Changes in management.

Does capsule endoscopy impact clinical management in established Crohn's disease?

BackgroundCapsule endoscopy (SBCE) has developed a relevant role in patients with established Crohn's Disease (CD). However, evaluation of the impact in clinical management has been scarce. AimsTo evaluate therapeutic impact of SBCE in an 11-year real-life cohort of known CD patients. MethodsRetrospective single center study including all patients with established CD submitted to SBCE procedure from 01/01/2008 to 31/12/2019. Patency capsule was used in selected patients. Small bowel mucosal inflammation was quantified using Lewis score. Therapeutic impact was defined as a change in CD-related treatment recommended based on SBCE results. Patients were assigned to four groups regarding SBCE indication: staging, flare, post-op and remission. ResultsFrom the 432 SBCE performed 87.5% were conclusive. Active disease was present in 63.7 of patients; 41.6% mild inflammation and 21.9% moderate-to-severe activity. A change of management was guided by SBCE in 51.3% of procedures: 199 (46.1%) escalation and 23 (5.3%) de-escalation, with significant changes in all groups. Escalation increased with disease activity: 57.8% in mild and 89.5% in moderate-to-severe disease. De-escalation was conducted in 13.9% procedures with mucosal healing and 1.1% with mild disease. ConclusionSBCE is a useful tool for guiding therapeutic management in CD patients both for treatment escalation and de-escalation.