Changes In Clinical Management Research Articles

Abstract 4136952: The Clinical Importance of Arrhythmia Notifications During Use of Wearable Cardioverter Defibrillator

Introduction: Wearable cardioverter defibrillators (WCDs) record continuous ECG data for the purpose of delivering treatment for lethal arrhythmias, but occasionally capture non-treatable arrhythmias that may be of clinical value. The purpose of this study was to evaluate the usefulness to health care providers (HCPs) of evaluating and reporting these other recorded ECGs and the impact on additional arrhythmia detection and clinical management decisions. Research Questions: Do clinicians find arrhythmias identified during routine WCD useful? What arrhythmias are observed? Can the identification of these arrhythmias, validation through ZOLL’s Independent Diagnostic Testing Facility (IDTF) and notification to the provider lead to changes in clinical management? Methods: A multi-center, observational study of 52 US HCPs enrolled 474 patients with commercial LifeVest prescriptions and followed them for up to 3 months. All routinely transmitted LifeVest ECG strips (corresponding to Baseline, Patient Initiated, or other automatic event recordings) during this period were analyzed by ECG technicians at the IDTF within ZOLL. These arrhythmias were reported to the HCP who completed a questionnaire assessing the utility (scored 1 to 5) and clinical impact (medication changes, tests, and procedures ordered) of these events. Results: At the conclusion of the study, 22% of patients (105/474) monitored had 112 reportable, unique arrhythmia events that were sent to 34 providers who completed questionnaires regarding report utility and clinical management decisions. A significant proportion of reports led to medication changes (40%), additional testing (32%) and procedural interventions (23%). The average usefulness of the reports was 3.63/5 with atrial fibrillation representing the most common arrhythmia, but many variations of ventricular ectopy were also captured which tended to be more clinically useful and impactful. Conclusions: WCD patients experience a high burden of actionable arrhythmias. Monitoring and reporting these arrhythmias over the course of normal wear provides additional clinical value to providers. Those arrhythmias that lead to changes to clinical management are the most useful.

NIMG-14. HEAD-TO-HEAD COMPARISON OF18F-FET PET AND68GA-PSMA-11 PET IN DISTINGUISHING SMALL VOLUME TUMOR PROGRESSION VS TREATMENT-RELATED CHANGE IN POST-STANDARD OF CARE TREATMENT OF HIGH-GRADE GLIOMA USING DYNAMIC ACQUISITION AND KINETIC MODELING

Abstract BACKGROUND The inability to accurately distinguish between tumor progression and treatment-related changes in patients with high-grade glioma on routine imaging can negatively impact patient management and in some cases, outcome. Various imaging methods have been used to address this issue, including 18F-fluoro-ethyl-tyrosine (FET) PET and MR perfusion. However, these methods may not provide reliable results in cases of small lesion size or hemorrhage within the treatment site. The prostate-specific membrane antigen (PSMA) has been observed to be expressed by neovasculature in brain tumors. Since PSMA cannot cross the blood brain barrier, uptake of PSMA in the brain carries high-level of suspicion for residual tumor. Still, further work is needed to better understand PSMA uptake in the tumor bed following standard of care (SOC) treatment and to compare to currently available neuro-oncologic radiotracers, such as FET. We hypothesize that PSMA imaging of glioma neovasculature will provide unique diagnostic information that will aid in the differentiation of small volume tumor progression from treatment-related changes in the post-SOC treatment setting. METHODS Patients who underwent clinical Expanded Access PET/MR imaging with 18F-FET were re-imaged in a research protocol that collected a brain 68Ga-PSMA-11 PET/CT scan, as well as a repeat 18F-FET PET/CT. Kinetic modeling of dynamic radiotracer uptake was performed. Scans were assessed for correlation with subsequent imaging and changes in clinical management. RESULTS All PSMA scans that were performed were concordant with the initial clinical FET scan, subsequent imaging follow up and appropriate changes in clinical management. The PSMA-detected site was confirmed to be tumor in a single case with subsequent tissue sampling. One patient who was started on bevacizumab after their clinical FET demonstrated a significant decrease in uptake on the research FET scan, but persistent uptake on PSMA. CONCLUSION PSMA may effectively show tumor recurrence in post-SOC treatment high-grade glioma patients.

Exploring the Role of Genetic Testing in Decisions to Redirect Care in Critically Ill Infants.

Genetic disorders are a major determinant of morbidity and mortality within neonatal intensive care units (NICUs). Studies have found genetic testing in critically ill infants may lead to changes in clinical decisions such as pursuing end of life care. This study surveyed palliative care providers to explore the influence of genetic testing on decisions to redirect care in critically ill infants. This study was conducted retrospectively on cases who were admitted to the Level IV NICU at Primary Children's Hospital, underwent redirection to end of life care, and whose death date was between 2019-2023. A review of the case's electronic medical record was performed to construct a clinical case summary. The clinical summary and questionnaire were sent to the case's palliative care provider. Fifty-six cases were included in this study and 73% had genetic testing completed. Our results suggest the information from genetic testing played a relatively minor role in the decision to redirect care for cases with negative or uncertain genetic testing and positive genetic testing results, although the influence appeared higher in the latter group. Our results suggest the assumptions of several studies that genetic testing is responsible for changes in clinical management and cost savings, especially in cases of redirection of care may have been overestimated. Our results fill a critical gap in current literature and demonstrate the need for further investigation to clarify the direct role of genetic testing in clinical decisions in the NICU, especially related to redirection of care.

Policy and practice review consensus statements and clinical guidelines on managing pediatric trauma and orthopedics during the COVID-19 pandemic: a systematic review on the global response for future pandemics and public health crises.

The COVID-19 pandemic has been recognized as an unprecedented global health crisis. Over 7 million mortalities have been documented with many paediatric fatalities. Trauma and orthopaedic care, much like other specialities, were marginalized due to resource allocation during the pandemic which affected paediatric care. This is the first systematic review to centralise and compile the recommended published guidelines from professional bodies in principally English speaking countries on managing paediatric trauma and orthopaedic care. These guidelines will be required to be implemented sooner and more effectively in case of future pandemics with similar impact. A search was conducted on PubMed/MedLine, Cochrane Library and Embase using terms including p(a)ediatric or child* and/or COVID* or coronavirus or SARS-CoV-2 and/or trauma and/or orthop(a)edic* with a simplified MeSH heading [mh] in order to make the search as comprehensive as possible. General terminology was utilized to make the search as exhaustive as possible for this systematic review. Another search was conducted on resources available in the public domain from professional bodies publishing on consensus statements and clinical practice guidelines in countries where English is the principal language managing pediatric trauma and orthopedics. The review adhered to PRISMA guidance. The search revealed a total of 62 results from both databases and professional bodies. Duplicates were removed. This was then reviewed to identify a total of 21 results which fit the inclusion criteria and included within the main analysis. The guidelines from professional bodies were outlined and categorized into aspects of clinical care. The impact of COVID-19 pandemic has compelled for changes in clinical practice and pediatric management. The systematic review highlights the relevant guidelines on service provision for pediatric patients including indications for urgent referrals, surgical prioritization, reasons for follow-up and trauma guidelines. The rationale for care during the unpredictable evolution of the COVID-19 pandemic may have the potential to be translated and replicated in future pandemics of similar significance.

The Clinical Utility of Finding Unexpected Subclinical Spikes Detected by High-Density EEG During Neurodiagnostic Investigations.

This study aimed to analyze the frequency of unexpected subclinical spikes (USCS) in pediatric patients who underwent high-density electroencephalogram (HD-EEG). Of the 4481 successful HD-EEG studies, 18.5% (829) were abnormal, and 49.7% of these abnormal studies showed SCS, of which 64.1% were USCS. USCS were found to be correlated with attention/concentration deficits and executive dysfunction, often accompanied by the dual psychiatric diagnosis of ADHD. MRI revealed abnormal findings in 32.6% of the subjects with USCS, such as abnormal signal or signal hyperintensity in brain parenchyma, temporal or arachnoid cysts, and vascular malformations. Moreover, the USCS group who received neuropsychiatric testing scored lower than the population mean on Full-Scale Intelligence Quotient, Working Memory Index, and Processing Speed Index. This study highlights the potential of USCS as biomarkers that can lead to changes in clinical management and outcomes, provide valuable information about pathophysiological mechanisms, and suggest potential treatment pathways.

Rapid Whole-Genome Sequencing in Acutely Ill Children: A Single Pediatric Center Experience

AbstractThe aim of this study was to describe the turnaround time, diagnostic yield, and clinical impact of rapid whole-genomic sequencing (rWGS). We conducted a prospective observational study in acutely ill children (0–21 years) with an undiagnosed, potentially genetic abnormality in a children's hospital. A phenotype-prioritized analysis approach for rWGS was utilized. The turnaround times, diagnostic yield, number of genes detected, inheritance pattern, zygosity, and the clinical impact of positive or negative tests were analyzed. Out of a total of 109 children, 92 abnormal (pathogenic or likely pathogenic) gene variants were detected in 60 (55%) patients. There were 45 neonates, 35 infants, and 29 children. The admission location was 49.5, 34.9, and 15.6% in the pediatric intensive care unit (PICU), neonatal intensive care unit (NICU), and cardiac intensive care unit (CICU), respectively. The median (interquartile range [IQR]) times for the return of preliminary and final results were 3 (2–5) and 10 (6–14) days, respectively. With ultra-rapid processing, the median time to final results was shorter (5 [3–7] vs. 12 [7.75–15] days). Neurologic issues were the most common underlying admission diagnoses. The diagnostic yield for a causative gene was 47.7%. The diagnostic yield was not different based on age group or location of admission but higher in metabolic issues (78.6 vs. 43.2%; odds ratio [OR]: 4.8; 95% confidence interval [CI]: 1.3–18.4). There was a change in clinical management in 39.4%. In acutely ill children with undiagnosed conditions and with clinical suspicion of a genetic disorder, rWGS detected gene variants in 55% with a diagnostic yield of 47.7% and resulted in a change in the management in 39.4%. The diagnostic yield in patients with metabolic conditions was the highest.

18F-FDG-PET/CT in breast cancer imaging: Restaging and Implications for treatment decisions in a clinical practice setting.

Although the diagnostic accuracy of 18F-fluorodeoxyglucose - positron emission tomography/computed tomography (18F-FDG-PET/CT) for breast cancer (BC) has been well studied, few studies have evaluated the impact of 18F-FDG-PET/CT on BC patient care. This study aimed to investigate restaging and 18F-FDG-PET/CT-induced changes in clinical decision-making in patients with BC. We retrospectively evaluated 18F-FDG-PET/CT-scans performed for BC-related indications in a prospectively collected consecutive cohort of adult patients at Skane University Hospital, Sweden. Patients with all BC stages were included and divided into three groups based on the indication for 18F-FDG-PET/CT: Group A (primary staging), Group B (response evaluation), and Group C (recurrence). The impact of 18F-FDG-PET/CT-scans on clinical management was categorized as no change, minor change (e.g. modification of treatment plans), or major change (e.g. shift from curative to palliative treatment intention). A total of 376 scans (151 patients) were included: Group A 9.3% (35 of 376 scans), Group B 77.4% (291 of 376 scans), and Group C 13.3% (50 of 376 scans). Significant stage migration, predominantly upstaging, occurred in Group A (45.7%) and Group C (28.0%). Changes in clinical management were observed in 120 scans (31.9%), of which 66 were major and 54 were minor. The largest proportion of 18F-FDG-PET/CT-induced management changes were observed in Group A (57.1%), most commonly a shift from curative to palliative treatment intention due to upstaging. Our study indicates the clinical utility of 18F-FDG-PET/CT in BC restaging and changes in clinical management; the latter observed in approximately one-third of all cases.

Clinician-Reported Management Recommendations in Response to Universal Germline Genetic Testing in Patients With Prostate Cancer.

Identification of pathogenic germline variants in patients with prostate cancer can help inform treatment selection, screening for secondary malignancies, and cascade testing. Limited real-world data are available on clinician recommendations following germline genetic testing in patients with prostate cancer. Patient data and clinician recommendations were collected from unselected patients with prostate cancer who underwent germline testing through the PROCLAIM trial. Differences among groups of patients were determined by 2-tailed Fisher's exact test with significance set at P < .05. Logistic regression was performed to assess the influence of test results in clinical decision-making while controlling for time of diagnosis (newly vs previously diagnosed). Among 982 patients, 100 (10%) were positive (>1 pathogenic germline variant), 482 (49%) had uncertain results (>1 variant of uncertain significance), and 400 (41%) were negative. Patients with positive results were significantly more likely than those with negative or uncertain results to receive recommendations for treatment changes (18% vs 1.4%, P < .001), follow-up changes (64% vs 11%, P < .001), and cascade testing (71% vs 5.4%, P < .001). Logistic regression demonstrated that positive and uncertain results were significantly associated with both changes to treatment and follow-up (P < .001) when controlling for new or previous diagnosis. Germline genetic testing results informed clinical recommendations for patients with prostate cancer, especially in patients with positive results. Higher than anticipated rates of clinical management changes in patients with uncertain results highlight the need for increased genetic education of clinicians treating patients with prostate cancer.

Appropriateness and outcomes of hospitalized patients telemetry monitored for cardiac arrhythmias in accordance with the American Heart Association Practice Standards–A multicenter study

BackgroundTo the best of our knowledge, no prospective research studies have compared clinical practice to the American Heart Association (AHA) updated practice standards for in-hospital telemetry monitoring. ObjectivesOur aims were therefore (1) to investigate how patients were assigned to telemetry monitoring in accordance with the AHA's updated practice standards, (2) to determine the number and type of arrhythmic events, and (3) to describe subsequent changes in clinical management. MethodsThis prospective multicenter study included 1154 patients at three university hospitals in Norway. Data were collected 24/7 over a four-week period, with follow-up measurements from telemetry admission until hospital discharge. ResultsOf patients assigned to telemetry, 67 % (n = 767) met practice standards, corresponding to AHA Class I or II. Patients were predominantly men (65 %, n = 748), and the mean age was 65 years (SD ±16). The study included both patients with cardiac and non-cardiac diagnoses from various medical and surgical departments throughout the hospitals. Ninety-one percent of the patients in Class III were monitored based on indications that were reclassified from Class II to Class III (not indicated) in the updated practice standards (patients admitted with chest pain or post-percutaneous coronary intervention (PCI) without complications). Overall, arrhythmic events occurred in 37 % (n = 424) of patients, and they occurred in all classes. Eighteen percent (n = 59) of arrhythmic events occurred in Class III. Of all arrhythmias, 3 % (n = 14) were life threatening, and all of them occurring within Class I. Telemetry monitoring led to changes in clinical management in 22 % (n = 257) of patients due to clinical alarms, of which 71 % (n = 182) were related to medication management. ConclusionsMost patients were appropriately monitored according to the AHA practice standards, meeting Class I and II. Arrhythmias occurred in all classes, but life-threatening arrhythmias only occurred in patients in Class I. However, a daily re-assessment of each patient's telemetry indication is warranted.

Changes in pituitary adenoma patient presentation and outcomes during the COVID pandemic at a Pituitary Center of Excellence.

The COVID-19 pandemic caused significant disruption to the surgical care of patients. The aim of this study was to analyze the impact of the pandemic on endoscopic endonasal surgery (EES) for patients with a pituitary adenoma. Patients from 2015 to 2022 that had EES for a pituitary adenoma were included in this study. Patients were separated into pre-COVID (January 2015-March 2020) and COVID (March 2020-September 2022) groups. Univariate analysis was done using chi-square, fisher exact tests, and t-tests to compare groups. This study included 492 patients that had EES for their pituitary adenoma. There were 314 patients in the pre-COVID group and 178 patients in the COVID group. Patients in the COVID group had a higher risk analysis index (RAI) frailty score (15 ± 10 pre-COVID vs. 20 ± 9 COVID, P < 0.001) and a higher American Society of Anesthesiology (ASA)physical status score (3 or 4) (72.0% pre-COVID vs. 81.9% COVID, P = 0.02). There were significantly more macroadenoma cases (87.6% pre-COVID vs. 94.4% COVID, P = 0.02) and extrasellar surgical approaches (45.2% pre-COVID vs. 61.2% COVID, P < 0.001) during COVID. There was no significant difference in length of stay (LOS) and readmission rates between groups. Patients that presented during the pandemic tended to be more frail, have more comorbidities, and require additional extrasellar surgical approaches. Despite changes in clinical presentation and operative management, the LOS and readmission rate remained stable during COVID, supporting the safety of this procedure during the recent pandemic.

Racial differences in serological markers across the first year of injury in spinal cord injury: a retrospective analysis of a multi-center interventional study

Study designSecondary analysis of a randomized, multi-center, placebo-controlled study(Sygen®).ObjectivesTo evaluate racial differences in serological markers in individuals with spinal cord injury(SCI) across the first year of injury.SettingHospitals in North America.MethodsSerological markers (e.g.,cell count, liver, kidney, and pancreatic function, metabolism, and muscle damage) were assessed among 316 participants (247 White, 69 Black) at admission, weeks 1, 2, 4, 8, and 52 post-injury. Linear mixed models were employed to explore the main effects of time, race (Black vs. White), and their interaction, with adjustment of covariates such as study center, polytrauma, injury (level, completeness), treatment group, and sex.ResultsA main effect of race was observed where White individuals had higher alanine transaminase, blood urea nitrogen(BUN), BUN/Creatinine ratio, sodium, and chloride, while Black individuals had higher calcium, total serum protein, and platelets. For markers with interaction effects, post-hoc comparisons showed that at week 52, White individuals had higher mature neutrophils, hematocrit, hemoglobin, mean corpuscular hemoglobin, albumin, and triglycerides, and Black individuals had higher amylase. Eosinophils, monocytes, red blood cells, aspartate aminotransferase, bilirubin, cholesterol, partial thromboplastin time, urine specific gravity, urine pH, CO2, and inorganic phosphorus did not differ between races.ConclusionsOur results revealed racial differences in serological markers and underscores the importance of considering race as a determinant of physiological responses. Future studies are warranted to explore the causes and implications of these racial disparities to facilitate tailored clinical management and social policy changes that can improve health equity.

Impact and Safety of Diagnostic Stewardship to Improve Urine Culture Testing Among Patients with Indwelling Urinary Catheters

Background: Indiscriminate urine culturing of patients with indwelling urinary catheters may lead to overdiagnosis of urinary tract infections, resulting in unnecessary antibiotic treatment and inaccurate reporting of catheter-associated urinary tract infections (CAUTIs) as a hospital quality metric. We evaluated the impact of a computerized diagnostic stewardship intervention to improve urine culture testing among patients with indwelling urinary catheters. Methods: We performed a single-center retrospective observational study at Rush University Medical Center from April 2018 – July 2023. In February 2021, we implemented a computerized clinical decision support tool to promote adherence to our internal urine culture guidelines for patients with indwelling urinary catheters. Providers were required to select one guideline criteria: 1) neutropenia, 2) kidney transplant, 3) recent urologic procedure, 4) urinary tract obstruction; or if none of the criteria were met, then an infectious diseases consultation was required for approval. We compared facility-wide CAUTI rate per 10,000 catheter days and standardized infection ratio (SIR) during baseline and intervention periods using ecologic models, controlling for time and for monthly Covid-19 hospitalizations. In the intervention period, we evaluated how providers responded to the intervention. Potential harm was defined as collection of a urine culture within 7 days of the intervention that resulted in a change in clinical management. Results: In unadjusted models, CAUTI rate decreased from 12.5 to 7.6 per 10,000 catheter days (p=0.04) and SIR decreased from 0.77 to 0.49 (p=0.09) during baseline vs intervention periods. In adjusted models, the CAUTI rate decreased from 6.9 to 5.5 per 10,000 catheter days (p=0.60) (Figure 1) and SIR decreased from 0.41 to 0.35 (p=0.65) during baseline vs intervention periods. Urine catheter standard utilization ratio (SUR) did not change (p=0.36). There were 598 patient encounters with ≥1 intervention. Selecting the first intervention for each encounter, 284 (47.5%) urine cultures met our guidelines for testing and 314 (52.5%) were averted (Figure 2). Of these, only 3 ( &lt; 1 %) had a urine culture collected in the subsequent 7 days that resulted in change in clinical management. Conclusion: We observed a trend of decreased CAUTIs over time, but effect of our diagnostic stewardship intervention was difficult to assess due to healthcare disruption caused by Covid-19. Adverse outcomes were rare among patients who had a urine culture averted. A computerized clinical decision support tool may be safe and effective as part of a multimodal program to reduce unnecessary urine cultures in patients with indwelling urinary catheters.

Real world management of individuals with severe FXI deficiency and its impact on clinical outcomes: Experience from a haemophilia treatment centre.

The management of Factor XI deficiency is challenged by a variable association between FXI level and bleeding phenotype. Additionally, there is scarce data describing management strategies and their outcomes, specifically bleeding, thrombosis, and other complications. To evaluate bleeding, thrombosis, and other complications in individuals with severe FXI deficiency seen in our comprehensive haemophilia treatment centre (HTC). Peri-procedural management strategies and the resulting impact on bleeding and other clinically relevant outcomes were reported. Retrospective review of the electronic medical record of adult patients with severe FXI deficiency (<20% activity) seen at a New York City comprehensive HTC between 2017 and 2022. Procedures, haemostatic management, and outcomes were collected and analysed. We identified 38 individuals (64%) females with severe FXI deficiency. The mean age was 56±21 years (SD). The median FXI activity level was 3% (IQR: 1-8%). The mean BAT score was 3.1±2.4; (52%) individuals did not have a history of bleeding. A total of 256 surgeries and procedures were performed. There was reduced bleeding with preventative or reactive treatment during procedures. Arterial but not venous thrombotic complications were observed. Plasma was mostly used for procedures associated with higher risk of bleeding and antifibrinolytics for procedures at sites of high fibrinolysis. Current management strategies pose a burden of care for these patients and manifested as nonbleeding adverse events and changes in clinical management. These findings highlight the need for novel investigation in predicting and managing bleeding for individuals with severe FXI deficiency.

Replacing post–chest tube removal chest radiographs with clinical assessment in adult thoracic surgery patients: A single-center prospective study

ObjectiveThe necessity and utility of chest radiographs in the absence of clinical symptoms have been questioned after chest tube removal. This study aimed to evaluate the impact of replacing routine chest radiographs after chest tube removal with clinical observation on outcomes in patients undergoing elective thoracic surgery. MethodsThis was a single-center prospective study of adult patients undergoing elective lung resection. Standard chest radiographs after chest tube removal were replaced with a clinical observation protocol for 2 hours after removal. Chest radiographs after chest tube removal were meant to be obtained only for symptomatic patients. The primary outcome was the incidence of adverse events related to this change. Secondary outcomes included changes in clinical management, length of stay, and postoperative complications. ResultsA total of 248 patients were included in the study period, and the majority (n = 185, 75%) did not have chest radiographs after chest tube removal. There was no significant difference in the incidence of adverse events or postoperative complications between patients who received chest radiographs and those who did not. Additionally, length of stay was significantly shorter in patients who did not receive chest radiographs (median 2.3 vs 3 days; P < .05). ConclusionsClinical observation can safely replace routine chest radiographs after chest tube removal in asymptomatic patients undergoing elective thoracic surgery. This approach may lead to shorter hospital stays and reduced healthcare costs without compromising patient safety. The findings support a clinically driven use of postoperative imaging in this patient population, highlighting the importance of individualized patient care.

OTHR-11. TITLE: ELECTROGRAPHIC SEIZURES AND EEG BACKGROUND FEATURES IN PEDIATRIC NEURO-ONCOLOGY PATIENTS ADMITTED TO THE PEDIATRIC INTENSIVE CARE UNIT

Abstract BACKGROUND Electrographic seizures (ES) are common in critically ill children with the incidence of ES ranging from 10-50%. Continuous EEG (cEEG) is frequently obtained in children with brain tumors due to encephalopathy or concern for seizures. Despite this, little is known about the incidence of ES, EEG background features, or the impact of EEG on clinical management in this population. METHODS This is a prospective single center study of critically ill children with brain tumors admitted to the pediatric intensive care unit (PICU) from July 2021 to July 2023. Patients with new or known primary brain tumors and cEEG completed during their admission were included. We excluded patients with planned admissions for EEG. Clinical variables included age, sex, oncologic diagnosis, tumor grade and location, indication for EEG, EEG features, and changes in management. RESULTS Thirty-six patients were identified who met the inclusion criteria. 21 patients were female. The median age was 11.0 years (IQR 6.6– 15.4 years). The most common indication for EEG was encephalopathy in 42% followed by clinical seizure in 31%. ES were captured in 19% (7/36) with the majority being subclinical; in patients with acute encephalopathy, ES were captured in 20% (3/15). The EEG background was abnormal in 97% of cases. The most common EEG background was slow disorganized with background asymmetry seen in in 74%. EEG background features met criteria for the ictal-interictal continuum in 14%. A higher rate of ES was seen in patients with disseminated tumors (p=0.03) and severe encephalopathy on EEG (p=0.006). EEG led to a change in management in 31% of patients. CONCLUSIONS ES are common in critically ill children with brain tumors and would go undetected without cEEG. EEG findings often led to a change in clinical management and is a vital tool for the evaluation of this population.

A reassessment of the clinical utility of 68Ga-DOTATATE PET/CT in patients with gastroenteropancreatic neuroendocrine tumors.

e16294 Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a rare and biologically diverse group of tumors that can be challenging to image. Gallium-68 (Ga-68) DOTATATE positron emission tomography/computed tomography (PET/CT) is the most sensitive imaging tool for these tumors and has now been in clinical practice for over a decade. While its use has increased over time, its clinical impact remains unclear for specific stages of disease and indications for imaging. We sought to investigate this to provide information to guide its future use in clinical management. Methods: This retrospective cohort study identified adults with pathologically confirmed GEP-NETs between 1/1/2020 and 9/1/2022 at a tertiary care academic medical center. The electronic medical record was reviewed for demographic, clinical, and radiographic data. The primary objective was to determine if the use of 68Ga-DOTATATE PET/CT was associated with a change in clinical management, medical or surgical. The secondary objective was to determine if 68Ga-DOTATATE PET/CT was more effective in identifying primary or metastatic lesions compared to traditional imaging such as CT or magnetic resonance imaging (MRI) performed less than 90 days of the PET/CT scan. Percentages are reported with 95% Confidence Intervals (CI). Results: Overall, 124 patients with pathologically confirmed GEP NETs underwent a total of 207 68Ga-DOTATATE PET/CT scans. The majority (92.7%) of GEP NETs were moderately/well differentiated and the primary sites included the small intestine (50%), pancreas (23.4%), appendix/colon (8.9%), gastric (8.1%), mesentery (2.4%), and unknown (7.3%). Following PET/CT scan, 51 patients (41.1%; 95% CI = 32.4-49.8) had a change in clinical management, with the proportion of patients who had a change being higher among those with metastatic disease (44.9% vs 14.5%). Of the 124, 72 patients had traditional imaging 90 days or less prior to PET/CT available for comparison. In this subgroup, 34 patients (47.2%; 95% CI = 35.7-58.7) had new lesions identified on PET/CT that were not identified using traditional imaging and of the 34 patients with new lesions identified, 79.4% (95% CI = 66-93) had a change in their clinical management. The majority of these patients had M1 disease (50% vs 15.4%). Conclusions: This study highlights the impact of 68Ga-DOTATATE PET/CT imaging in the clinical management of patients with gastroenteropancreatic neuroendocrine tumors (GEP NETs). Notably this imaging technique resulted in a change in clinical management for 41% of these patients, particularly benefiting those with metastatic (M1) disease, where the change in management was more pronounced (44.9% vs. 14.5%). Furthermore, 68Ga-DOTATATE PET/CT proved superior to traditional imaging revealing new lesions in 47.2% of the patients, with the majority being patients with metastatic disease.

The Impact of Second Opinion Expert Pathology Review in Patient Management at the Time of Transurethral Resection of the Bladder

Background and objectivePathological features in non–muscle-invasive bladder cancer specimens are pivotal in determining correct patients’ therapeutic management. Sparse data exist regarding the importance of second opinion performed by an expert uropathologist. This study aimed to assess the importance of a second opinion by an expert uropathologist in the management of bladder cancer. MethodsThe study relied on 272 bladder cancer specimens from 231 patients seeking a pathology second opinion after transurethral resection of the bladder for a clinical suspicion of bladder cancer, relapse, or second-look procedure. Pathology second opinion was offered by an experienced fellowship-trained uropathologist. Discrepancies were recorded considering primary tumor staging, the presence of muscularis propria, and the presence of histological variants. Cases were categorized as no significant discordance, major discordance without management change, and major discordance with management change according to the European Urology Association (EAU) guidelines. Key findings and limitationsAmong 272 second opinion cases, 39% (108/272) had major discordance and 28% (75/272) had major discordance with change in management according to the EAU guidelines. Upstaging and downstaging were reported in 66 (24%) patients. Improper identification of the presence of muscularis propria was found in 46 (17%) cases, of which 11 (4%) were deemed clinically relevant. Differences regarding the presence of histological variants were diagnosed in 40 cases (15%), resulting in eight (3%) changes in clinical management. In ten specimens (4%), multiple clinically relevant discrepancies were found. Conclusions and clinical implicationsThe second opinion evaluation changed the clinical management in 25% of the cases. These results support the importance of specimen review by an expert uropathologist as a major driver in the correct bladder cancer management. Patient summaryWe investigated the importance of a second opinion performed by an expert uropathologist in the management of bladder cancer. We found that 25% had their treatment plan changed due to the revised pathological report.

Clinical Impact of Telomere Length Testing for Interstitial Lung Disease

BackgroundShortened telomere length (TL) is a genomic risk factor for fibrotic interstitial lung disease (ILD), but its role in clinical management is unknown. Research QuestionWhat is the clinical impact of TL testing on the management of ILD? Study Design and MethodsPatients were evaluated in the Columbia University ILD clinic and underwent CLIA-certified TL testing by flow cytometry and fluorescence in-situ hybridization (FlowFISH) as part of clinical management. Short TL was defined as below the 10th age-adjusted percentile for either granulocytes or lymphocytes by FlowFISH. Patients were offered genetic counseling and testing if they had short TL or a family history of ILD. FlowFISH TL was compared against research qPCR TL measurement. ResultsA total of 108 patients underwent TL testing, including those with clinical features of short telomere syndrome such as familial pulmonary fibrosis (50%) or extrapulmonary manifestations in the patient (25%) or a relative (41%). The overall prevalence of short TL was 46% and was similar across clinical ILD diagnoses. The number of short telomere clinical features was independently associated with detecting short TL (OR 2.00, 95% CI [1.27, 3.32]). TL testing led to clinical management changes for 35 (32%) patients, most commonly resulting in reduction or avoidance of immunosuppression. Of the patients who underwent genetic testing (n=34), a positive or candidate diagnostic finding in telomere-related genes was identified in 10 (29%) patients. Inclusion of TL testing below the 1st percentile helped reclassify 8 of 9 variants of uncertain significance (VUS) into actionable findings. The qPCR test correlated with FlowFISH, but age-adjusted percentile cutoffs may not be equivalent between the two assays. InterpretationIncorporating TL testing in ILD impacted clinical management and led to the discovery of new actionable genetic variants.

Evolution of invasive pneumococcal disease by serotype 3 in adults: a Spanish three-decade retrospective study

Invasive pneumococcal disease due to serotype 3 (S3-IPD) is associated with high mortality rates and long-term adverse effects. The introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) into the Spanish paediatric immunisation programme has not led to a decrease in the adult S3-IPD. We aimed to analyse the incidence, clinical characteristics and genomics of S3-IPD in adults in Spain. Adult IPD episodes hospitalized in a Southern Barcelona hospital were prospectively collected (1994-2020). For genomic comparison, S3-IPD isolates from six Spanish hospitals (2008-2020) and historical isolates (1989-1993) were analysed by WGS (Illumina and/or MinION). From 1994 to 2020, 270 S3-IPD episodes were detected. When comparing pre-PCV (1994-2001) and late-PCV13 (2016-2020) periods, only modest changes in S3-IPD were observed (from 1.58 to 1.28 episodes per 100,000 inhabitants year). In this period, the incidence of the two main lineages shifted from 0.38 to 0.67 (CC180-GPSC12) and from 1.18 to 0.55 (CC260-GPSC83). The overall 30-day mortality remained high (24.1%), though a decrease was observed between the pre-PCV (32.4%; 95.0% CI, 22.0-45.0) and the late-PCV13 period (16.7%; 95.0% CI, 7.5-32.0) (p=0.06). At the same time, comorbidities increased from 77.3% (95.0% CI, 65.0-86.0) to 85.7% (95.0% CI, 71.0-94.0) (p=0.69). There were no differences in clinical characteristics or 30-day mortality between the two S3 lineages. Although both lineages were genetically homogeneous, the CC180-GPSC12 lineage presented a higher SNP density, a more open pan-genome, and a major presence of prophages and mobile genetic elements carrying resistance genes. Adult S3-IPD remained stable in our area over the study period despite PCV13 introduction in children. However, a clonal shift was observed. The decrease in mortality rates and the increase in comorbidities suggest a change in clinical management and overall population characteristics. The low genetic variability and absence of clinical differences between lineages highlight the role of the S3 capsule in the disease severity. This study has been funded by Instituto de Salud Carlos III (ISCIII) "PI18/00339", "PI21/01000", "INT22/00096", "FI22/00279", CIBER "CIBERES-CB06/06/0037", "CIBERINFEC-CB21/13/00009" and MSD grant "IISP 60168".

Abstract PO1-09-03: Clinical Impact of Multigene Panel Testing in Patients with a Personal or Family History of Breast or Ovarian Cancer Previously Negative for BRCA1/2 Genes

Abstract Rapid developments in cancer genetics and hereditary cancer risk assessments have enabled the identification of individuals at elevated risk for hereditary malignancies to guide enhanced cancer screening and prevention efforts. Multigene panel testing has emerged as the standard approach as emphasized in the National Comprehensive Cancer Network (NCCN) guidelines. The purpose of this study was to investigate the frequency of other pathogenic mutations identified through multigene panel testing in individuals who previously tested negative for germline BRCA1/2 and assess the clinical impact of panel testing. Patients either previously diagnosed with breast cancer or with a family history of breast or ovarian cancer that had also been seen by Oncology Genetics at a single institution and tested negative for BRCA1/2 genes but had not undergone prior multigene panel testing were invited via a letter to return for an additional genetic counseling visit to discuss multigene panel testing. Patients were also able to opt-in to a survey component of the study and received an email to fill out the Multidimensional Impact of Cancer Risk Assessment (MICRA) and Cancer Worry Scale (CWS). Surveys were completed prior to the initial genetic counseling appointment and repeated after discussion of the multigene panel test results. A total 24 women met with a genetic counselor of which 22 (92%) had a personal history of breast cancer, 1 (4%) had a family history of breast cancer, and 1 (4%) had a family history of ovarian cancer. The mean age was 52.6 years (range, 42-68) and 100% of women were Caucasian. Of the 24 women, 17 (71%) completed multigene panel testing. Of the women that underwent testing, 7 (41%) had negative results, 6 (35%) had variants of unknown significance (VUS), and 4 (24%) had a pathogenic mutation identified in another gene (CDKN2A, CHEK2, and CFTR). There was no significant change in MICRA or CWS scores after multigene panel results were reviewed in the 9 patients that completed both pre- and post-genetic testing surveys. The mean/median summary MICRA scores pre- and post-counselling were 30 (SD 12.4), median 26 (min 18, max 56), and 21.2 (SD 15.4), median 21 (min 3, max 43), respectively (p=0.19, Wilcoxon signed ranks test). The mean/median summary CWS scores pre- and post-counselling were 14.3 (SD 5), median 15 (min 7, max 24), and 13.6 (SD 2.59), median 14 (min 10, max 17), respectively (p=0.53, Wilcoxon signed ranks test). Of the 4 patients with newly identified pathogenic mutations, 2 started new screening protocols and 1 underwent a prophylactic mastectomy. In conclusion, multigene panel testing identified pathogenic mutations in a subset of individuals who previously tested negative for BRCA1/2 genes leading to changes in clinical management. The completion of multigene panel testing did not lead to a significant increase in MICRA or CWS scores. Key limitations of this study include a small sample size and an all Caucasian population. Citation Format: Devon Miller, Stephanie Pritzl, Angela Tess, Jessica Gooding, Lisa Barroilhet, Lori Dubenske, Kari Wisinski. Clinical Impact of Multigene Panel Testing in Patients with a Personal or Family History of Breast or Ovarian Cancer Previously Negative for BRCA1/2 Genes [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 PO1-09-03.