Changes In Clinical Management Research Articles

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

Secondary analysis of a randomized, multi-center, placebo-controlled study(Sygen®). To evaluate racial differences in serological markers in individuals with spinal cord injury(SCI) across the first year of injury. Hospitals in North America. Serological 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. A 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. Our 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.

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.

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.

Abstract PO1-08-04: Universal Germline Genetic Testing for Breast Cancer: Implementation in a Rural Practice and Impact on Shared Decision Making

Abstract Background: Prior work from our group has shown a high rate of familial breast cancer (BC) among rural BC patients (pts), with 33% reporting > 1 first-degree family members with BC and 55% meeting NCCN germline genetic testing (GGT) criteria (Shelton CH et al. NC Med. J; 2022). In 2018, we increased GGT to include all BC pts and observed: 1) many pts were out-of-criteria per NCCN guidelines but had actionable pathogenic germline variants (PGVs) and 2) knowledge of GGT factored significantly into shared decision making by providers and patients, including for positive and negative results. Beginning in 2019, concurrent with the recommendation from the American Society of Breast Surgeons, we expanded this model of universal GGT to an IRB-approved study to measure the impact of prospective testing on shared decision-making. Herein we report the real-world implementation of universal GGT for patients with BC and genetics-informed treatment decision-making in a rural community practice. Methods: From 2019-2022 all BC pts at a small, rural community hospital were offered GGT. Demographics, clinical features, and GGT results were collected along with clinician-reported clinical recommendations for treatment based on GGT results. Descriptive statistics and two-tailed Fisher’s exact test were employed and significance was set at p< 0.05. Results: 210 BC pts were offered GGT and 192 (91%) underwent testing [97% female, 95% non-Hispanic White, mean age at diagnosis of 62, 75% Stage I], with all but 7 pts completing GGT before primary treatment decisions. 104 (54%) of patients were in-criteria (IC) and 88 (46%) out-of-criteria (OOC) with NCCN GGT guidelines. PGVs were identified in 25 pts (13%) and 15 genes, most commonly BRCA1/2 (5 pts), PALB2 (3), monoallelic MUTYH (3) and ATM, BARD1, CHEK2 (2 pts each). PGV frequencies were 15% in IC and 11% in OOC patients (p=0.495). 46 (24%) pts had only a variant of uncertain significance (VUS) results. 70% of patients had > 1 clinical management change based on their GGT results. Changes in breast surgery, uptake of risk-reducing bilateral salpingo-oophorectomy, surveillance and clinical follow-up were significantly higher in patients with PGV compared to those with VUS/negative results (p < 0.0001). Compared to those with negative results, patients with PGVs in BRCA1 and BRCA2 were significantly more likely to undergo bilateral mastectomy (BLM) while those with PGVs in other genes or with VUS were not significantly more likely to elect for BLM than those with negative results. Clinicians reported that return of GGT reinforced their recommendation for 73/138 (53%) of patients who underwent breast-conserving therapy. GGT results aided in radiation therapy strategy for 54% of pts, most often resulting in dose de-escalation (accelerated fractionation) for negative/VUS pts (Table). Conclusions: Universal GGT for patients with BC was successfully implemented in a rural community practice with >90% uptake. Treatment was enhanced in those with clinically actionable PGVs and de-escalated in those without PGVs. Universal GGT for patients with BC is feasible to implement as the standard of practice within rural populations, enabling optimization of clinical care to patients’ genetic profile and may reduce unnecessary healthcare resource utilization. Universal Germline Genetic Testing for Breast Cancer: Implementation in a Rural Practice and Impact on Shared Decision Making Changes in Radiation Therapy Strategy based on GGT Citation Format: Charles Shelton, Sarah Nielsen, Antonio Ruiz, Lauren Shelton, Karen Freas, Sarah Poll, Brandie Heald, Daniel Pineda-Alvarez, Edward Esplin, Rachel Ellsworth, Hannah Montgomery. Universal Germline Genetic Testing for Breast Cancer: Implementation in a Rural Practice and Impact on Shared Decision Making [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 PO1-08-04.

Late-Onset Findings During Extended EEG Monitoring Are Rare in Critically Ill Children.

Electrographic seizures (ES) are common in critically ill children undergoing continuous EEG (CEEG) monitoring, and previous studies have aimed to target limited CEEG resources to children at highest risk of ES. However, previous studies have relied on observational data in which the duration of CEEG was clinically determined. Thus, the incidence of late occurring ES is unknown. The authors aimed to assess the incidence of ES for 24 hours after discontinuation of clinically indicated CEEG. This was a single-center prospective study of nonconsecutive children with acute encephalopathy in the pediatric intensive care unit who underwent 24 hours of extended research EEG after the end of clinical CEEG. The authors assessed whether there were new findings that affected clinical management during the extended research EEG, including new-onset ES. Sixty-three subjects underwent extended research EEG. The median duration of the extended research EEG was 24.3 hours (interquartile range 24.0-25.3). Three subjects (5%) had an EEG change during the extended research EEG that resulted in a change in clinical management, including an increase in ES frequency, differential diagnosis of an event, and new interictal epileptiform discharges. No subjects had new-onset ES during the extended research EEG. No subjects experienced new-onset ES during the 24-hour extended research EEG period. This finding supports observational data that patients with late-onset ES are rare and suggests that ES prediction models derived from observational data are likely not substantially underrepresenting the incidence of late-onset ES after discontinuation of clinically indicated CEEG.

Rapid Whole-Genome Sequencing and Clinical Management in the PICU: A Multicenter Cohort, 2016-2023.

Analysis of the clinical utility of rapid whole-genome sequencing (rWGS) outside of the neonatal period is lacking. We describe the use of rWGS in PICU and cardiovascular ICU (CICU) patients across four institutions. Ambidirectional multisite cohort study. Four tertiary children's hospitals. Children 0-18 years old in the PICU or CICU who underwent rWGS analysis, from May 2016 to June 2023. None. A total of 133 patients underwent clinical, phenotype-driven rWGS analysis, 36 prospectively. A molecular diagnosis was identified in 79 patients (59%). Median (interquartile range [IQR]) age was 6 months (IQR 1.2 mo-4.6 yr). Median time for return of preliminary results was 3 days (IQR 2-4). In 79 patients with a molecular diagnosis, there was a change in ICU management in 19 patients (24%); and some change in clinical management in 63 patients (80%). Nondiagnosis changed management in 5 of 54 patients (9%). The clinical specialty ordering rWGS did not affect diagnostic rate. Factors associated with greater odds ratio (OR [95% CI]; OR [95% CI]) of diagnosis included dysmorphic features (OR 10.9 [95% CI, 1.8-105]) and congenital heart disease (OR 4.2 [95% CI, 1.3-16.8]). Variables associated with greater odds of changes in management included obtaining a genetic diagnosis (OR 16.6 [95% CI, 5.5-62]) and a shorter time to genetic result (OR 0.8 [95% CI, 0.76-0.9]). Surveys of pediatric intensivists indicated that rWGS-enhanced clinical prognostication (p < 0.0001) and contributed to a decision to consult palliative care (p < 0.02). In this 2016-2023 multiple-PICU/CICU cohort, we have shown that timely genetic diagnosis is feasible across institutions. Application of rWGS had a 59% (95% CI, 51-67%) rate of diagnostic yield and was associated with changes in critical care management and long-term patient management.

Pattern of Ultrasonographic Prescriptions and Findings in Rural Northern India: A Mixed Methods Study

Abstract Background: Ultrasonography (USG) is used extensively across countries to diagnose and manage diseases. However, the existing USG services must be utilised rationally and effectively. Aim: Understanding the pattern of USG prescriptions and findings is important for improving the quality of healthcare services delivered by any healthcare system. Patients and Methods: A mixed methods study was conducted at a rural sub-district hospital in northern India to assess the pattern and completeness of prescriptions and USG findings and explore the patient and doctor-related factors influencing the USG prescription practices. Results: Of the 505 patients studied, 324 (64.2%) were females. The median age was 32 years (interquartile range: 24–45 years). The availability of complete medical history and clinical examination recording was 471 (85.7%) and 145 (28.7%), respectively. The indication for USG was mentioned in 436 (86.3%) prescriptions. Of the total, 251 (49.7%) had abnormal ultrasound findings. The abnormal finding was significantly high amongst patients (a) aged 45–59 years (P = 0.015) and (b) referred from surgery, paediatrics and other outpatient departments (P = 0.001) after adjustment to other factors. Patient-related factors such as non-harmfulness, free availability, reassurance of normality and health system/provider-level factors such as absence or low awareness of guidelines and changed clinical practice were the reasons for the current pattern of USG prescriptions. Conclusion: Although the medical history is better recorded, the incomplete recording of clinical examination needs improvement. Placing a guideline for prescribing USG, imposing nominal user fees and patient education and counselling can be tested for effectively utilising the USG services. Further, tracking the change in clinical management following the USG in Indian setting is the need of the hour.

Clinical value of Alzheimer's disease biomarker testing.

In the Investigating the Impact of Alzheimer's Disease Diagnostics in British Columbia (IMPACT-AD BC) study, we aimed to understand how Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker testing-used in medical care-impacted medical decision-making (medical utility), personal decision-making (personal utility), and health system economics. The study was designed as an observational, longitudinal cohort study. A total of 149 patients were enrolled between February 2019 and July 2021. Patients referred to memory clinics were approached to participate if their dementia specialist ordered AD CSF biomarker testing as part of their routine medical care, and the clinical scenario met the appropriate use criteria for lumbar puncture and AD CSF biomarker testing. For the medical utility pillar, detailed clinical management plans were collected via physician questionnaires pre- and post-biomarker disclosure. Patients with completed management questionnaires (n = 142) had a median age of 64 (interquartile range: 59-69) years, 48% were female, and 60% had CSF biomarker profiles on the AD continuum. Clinical management changed in 89.4% of cases. AD biomarker testing was associated with decreased need for other diagnostic procedures, including brain imaging (-52.0%) and detailed neuropsychological assessments (-63.2%), increased referrals and counseling (57.0%), and guided AD-related drug prescriptions (+88.4% and -50.0% in biomarker-positive and -negative cases, respectively). AD biomarker testing was associated with significant and positive changes in clinical management, including decreased health care resource use, therapy optimization, and increased patient and family member counseling. While certain changes in management were linked to the AD biomarker profile (e.g., referral to clinical trials), the majority of changes were independent of baseline clinical presentation and level of cognitive impairment, demonstrating a broad value for AD biomarker testing in individuals meeting the appropriate use criteria for testing.

Utility of Follow-up Radiographs in Type 1 Supracondylar Humerus Fractures.

Supracondylar humerus (SCH) fractures are common among pediatric patients, with the severity categorized using the Gartland classification system. Type 1 SCH fractures are nondisplaced and treated with immobilization, while more displaced fractures require surgery. The need for follow-up radiographs, particularly for type 1 fractures, is an area where evidence is lacking. This study investigates the clinical value and financial implications of follow-up radiographs for type 1 SCH fractures, hypothesizing that they do not alter clinical management and, therefore, represent an unnecessary expense. This retrospective cohort study, approved by the Institutional Review Board, focused on patients under 18 with nondisplaced SCH fractures treated nonoperatively. One hundred one type 1 SCH fractures, in which the fracture was visible on presenting radiographs, were chosen from patients presenting between January 2021 and December 2022. Charts were reviewed for demographic information, time of cast removal, and complications. A pediatric orthopaedic surgeon and orthopaedic resident reviewed the radiographs to confirm the injury to be a type 1 SCH fracture. Among the 101 patients, after the initial presentation, 79 attended an interim visit and 101 attended a "3-week follow-up" at an average of 23 days postinjury. All patients underwent radiographs during these visits for a total of 180 radiographs after confirmation of type 1 SCH fracture. No changes in management resulted from follow-up radiographs. One instance of refracture was noted ~3 months after cast removal. There were 180 superfluous follow-up radiographs taken at subsequent clinic visits. The total charge for these radiographs was $76,001.40, averaging $752.49 per patient. Follow-up radiographs for type 1 SCH fractures did not lead to changes in clinical management, aligning with previous findings in more severe SCH fractures. This approach can reduce costs, radiation exposure, and clinic time without compromising patient care. The study can reassure providers and parents about the lack of necessity for follow-up radiographs to document healing. Level-IV.

Multi-center implementation of rapid whole genome sequencing provides additional evidence of its utility in the pediatric inpatient setting.

Multi-center implementation of rapid whole genome sequencing with assessment of the clinical utility of rapid whole genome sequencing (rWGS), including positive, negative and uncertain results, in admitted infants with a suspected genetic disease. rWGS tests were ordered at eight hospitals between November 2017 and April 2020. Investigators completed a survey of demographic data, Human Phenotype Ontology (HPO) terms, test results and impacts of results on clinical care. A total of 188 patients, on general hospital floors and intensive care unit (ICU) settings, underwent rWGS testing. Racial and ethnic characteristics of the tested infants were broadly representative of births in the country at large. 35% of infants received a diagnostic result in a median of 6 days. The most common HPO terms for tested infants indicated an abnormality of the nervous system, followed by the cardiovascular system, the digestive system, the respiratory system and the head and neck. Providers indicated a major change in clinical management because of rWGS for 32% of infants tested overall and 70% of those with a diagnostic result. Also, 7% of infants with a negative rWGS result and 23% with a variant of unknown significance (VUS) had a major change in management due to testing. Our study demonstrates that the implementation of rWGS is feasible across diverse institutions, and provides additional evidence to support the clinical utility of rWGS in a demographically representative sample of admitted infants and includes assessment of the clinical impact of uncertain rWGS results in addition to both positive and negative results.

Abstract WP124: Dual Energy Head CT Immediately Following Mechanical Thrombectomy Rarely Leads to Changes in Clinical Management

Introduction: No guidelines exist regarding imaging after mechanical thrombectomy (MT) for acute ischemic stroke (AIS). Dual Energy Head CT (DECT) can differentiate between contrast staining and intracranial hemorrhage (ICH). We obtained routine DECT for AIS patients immediately following MT. We aimed to understand the impact of DECT on clinical management. Methods: We conducted a single-center retrospective study of AIS patients who underwent MT and immediate post-procedure DECT between March 2021 and February 2023. Patients were grouped by whether or not DECT results changed management, compared to our standard post-thrombectomy protocol and as documented in clinical notes. Continuous variables were compared using Wilcoxon Rank-Sum tests, and categorical variables were compared using Chi-square tests. Results: Of 173 patients who met inclusion criteria, 13 (7.5%) had documented changes in management following DECT. Management changes included delayed anti-thrombotic administration, lowered systolic blood pressure goals, and serial imaging. There were no statistically significant differences in age, gender, initial NIHSS, ischemic core size pre-MT, or treated vessel between patients with and without a change in management. Patients with management changes were more likely to have had procedural complications, contrast staining, any ICH, and symptomatic ICH (Table). While 34 patients had ICH on DECT, this only led to a documented change in management for 11 (32.4%) patients. Conclusion: Routine DECT immediately after MT rarely changed clinical management. Immediate DECT may be reserved for patients with intraprocedural complications or those with clinical suspicion of ICH.

Inflammation—A Possible Link between Myocarditis and Arrhythmogenic Cardiomyopathy

Arrhythmogenic cardiomyopathy is a primary genetic disease caused by mutations in the desmosome genes. Ever since the introduction of new imaging techniques, like cardiovascular magnetic resonance, the diagnosis of arrhythmogenic cardiomyopathy has become more challenging as left ventricular or biventricular variants may have resemblance to other cardiomyopathies or myocarditis. Not only this but they may also share an acute phase, which might cause even more confusion and misdiagnoses and influence the prognosis and outcome. In this case report, we present a 31-year-old patient with multiple clinical pictures: his symptoms were acute chest pain, new onset of heart failure and arrhythmia symptoms, which determined a dynamic change in clinical diagnosis and management, ultimately taking into consideration arrhythmogenic cardiomyopathy. Through the article, we try to uncover and explain common pathophysiological pathways shared by arrhythmogenic cardiomyopathy and other clinical entities with a special focus on inflammation. The final question remains: “If there is more than one heart disorder that eventually leads to the same clinical image, one may wonder, is arrhythmogenic cardiomyopathy a syndrome rather than a specific condition?”.

Changes in Clinical Management Following 14-Day Ambulatory ECG Monitoring Following Emergency Department Evaluation for Unexplained Syncope

Changes in Clinical Management Following 14-Day Ambulatory ECG Monitoring Following Emergency Department Evaluation for Unexplained Syncope

Tumor-Informed Circulating Tumor DNA for Minimal Residual Disease Detection in the Management of Colorectal Cancer.

Recurrence after curative-intent treatment occurs in 20%-50% of patients with stage II-IV colorectal cancer (CRC), underscoring the need for early detection of minimal residual disease (MRD) using circulating tumor DNA (ctDNA). Here, we examined the pattern of use of a tumor-informed ctDNA assay in CRC MRD monitoring in routine clinical practice at Mayo Clinic, Rochester. We conducted a retrospective analysis of health records of patients with CRC who had at least one tumor-informed ctDNA assay from May 2019 through July 1, 2022. Recurrence was defined as radiographic evidence of disease. Descriptive characteristics of the cohort, ctDNA results, and subsequent interventions were recorded. Of the 120 patients included, the median age at diagnosis was 67 years, 46% were female, and 94% were White. At diagnosis, 10 patients had stage I, 23 stage II, 60 stage III, and 25 stage IV disease. Of 476 ctDNA assays performed, 70% were performed in patients who had recurrent disease most commonly to monitor the effectiveness of therapeutic interventions and 16% resulted in a change in clinical decision making. There were 110 recurrences identified in 62 patients, as some patients experienced more than one recurrence over time. Compared with serum carcinoembryonic antigen levels, ctDNA results correlated better with radiologic imaging. Routine ctDNA monitoring for MRD detection has been adopted in clinical practice; however, 84% of ctDNA assays performed did not result in a change in clinical management. This suggests the need for further clinical research data to guide routine clinical use of ctDNA MRD testing in CRC.

Thyroid and adrenal incidentalomas on chest CT: Prevalence, diagnostic work-up and outcomes in a cohort of COVID-19 suspected patients

ObjectiveDue to increased use of computed tomography (CT), prevalence of thyroid and adrenal incidentalomas is rising. Yet, previous studies on the outcomes of diagnostic work-up of incidentalomas are subjected to inclusion bias. Therefore, we aimed to investigate prevalence and outcomes of diagnostic work-up of thyroid and adrenal incidentalomas detected on chest CT in a less selected population of COVID-19 suspected patients. DesignA retrospective, observational cohort study. MethodsWe included all COVID-19 suspected patients who underwent chest CT between March 2020 and March 2021. Radiology reports and medical records were reviewed for the presence and subsequent diagnostic work-up of thyroid and adrenal incidentalomas. ResultsA total of 1,992 consecutive COVID-19 patients were included (59.4% male, median age 71 years [IQR: 71–80]). Thyroid and adrenal incidentalomas were identified in 95 (4.8%) and 133 (6.7%) patients, respectively. Higher prevalence was observed with increasing age, among female patients and in patients with malignancy. Forty-four incidentalomas were further analyzed, but no malignancies were found. Only three lesions were hormonally active (1 thyrotoxicosis and 2 mild autonomous cortisol secretion). Diagnostic work-up did not lead to any change in clinical management in 97.7% of the analyzed patients. ConclusionPrevalence rates of thyroid and adrenal incidentalomas on chest CT in a less selected COVID-19 cohort were 4.8% and 6.7%, respectively. Yet, as all incidentalomas turned out to be benign and only three lesions were (mildly) hormonally active, this raises the question whether intensive diagnostic work-up of incidentalomas is necessary in all patients.

Early genetic testing in pediatric epilepsy: Diagnostic and cost implications.

The identification of numerous genetically based epilepsies has resulted in the widespread use of genetic testing to inform epilepsy etiology. Our study aims to investigate whether a difference exists in the diagnostic evaluation and healthcare-related cost expenditures of pediatric patients with epilepsy of unknown etiology who receive a genetic diagnosis through multigene epilepsy panel (MEP) testing and comparing those who underwent early (EGT) versus late genetic testing (LGT). Testing was defined as early (less than 1 year), or late (more than 1 year), following clinical epilepsy diagnosis. A retrospective chart review of pediatric individuals (1-17 years) with epilepsy of unknown etiology who underwent multigene epilepsy panel (MEP) testing identified 28 of 226 (12%) individuals with a pathogenic epilepsy variant [EGT n = 8 (29%); LGT n = 20 (71%)]. The average time from clinical epilepsy diagnosis to genetic diagnosis was 0.25 years (EGT), compared with 7.1 years (LGT). The EGT cohort underwent fewer metabolic tests [EGT n = 0 (0%); LGT n = 16 (80%) (P < 0.01)] and invasive procedures [EGT n = 0 (0%); LGT n = 5 (25%) (P = 0.06)]. Clinical management changes implemented due to genetic diagnosis occurred in 10 (36%) patients [EGT n = 2 (25%); LGT n = 8 (40%) (P = 0.76)]. Early genetic testing with a MEP in pediatric patients with epilepsy of unknown etiology who receive a genetic diagnosis is associated with fewer non-diagnostic tests and invasive procedures and reduced estimated overall healthcare-related costs. PLAIN LANGUAGE SUMMARY: This study aims to investigate whether a difference exists in the diagnostic evaluation and cost expenditures of pediatric patients (1-17 years) with epilepsy of unknown cause who are ultimately diagnosed with a genetic cause of epilepsy through multigene epilepsy panel testing and comparing those who underwent early testing (less than 1 year) versus late testing (more than 1 year) after clinical epilepsy diagnosis. Of the 28 of 226 individuals with a confirmed genetic cause of epilepsy on multigene epilepsy panel testing, performing early testing was associated with fewer non-diagnostic tests, fewer invasive procedures and reduced estimated overall healthcare-related costs.

Dynamic updating of clinical survival prediction models in a changing environment

BackgroundOver time, the performance of clinical prediction models may deteriorate due to changes in clinical management, data quality, disease risk and/or patient mix. Such prediction models must be updated in order to remain useful. In this study, we investigate dynamic model updating of clinical survival prediction models. In contrast to discrete or one-time updating, dynamic updating refers to a repeated process for updating a prediction model with new data. We aim to extend previous research which focused largely on binary outcome prediction models by concentrating on time-to-event outcomes. We were motivated by the rapidly changing environment seen during the COVID-19 pandemic where mortality rates changed over time and new treatments and vaccines were introduced.MethodsWe illustrate three methods for dynamic model updating: Bayesian dynamic updating, recalibration, and full refitting. We use a simulation study to compare performance in a range of scenarios including changing mortality rates, predictors with low prevalence and the introduction of a new treatment. Next, the updating strategies were applied to a model for predicting 70-day COVID-19-related mortality using patient data from QResearch, an electronic health records database from general practices in the UK.ResultsIn simulated scenarios with mortality rates changing over time, all updating methods resulted in better calibration than not updating. Moreover, dynamic updating outperformed ad hoc updating. In the simulation scenario with a new predictor and a small updating dataset, Bayesian updating improved the C-index over not updating and refitting. In the motivating example with a rare outcome, no single updating method offered the best performance.ConclusionsWe found that a dynamic updating process outperformed one-time discrete updating in the simulations. Bayesian updating offered good performance overall, even in scenarios with new predictors and few events. Intercept recalibration was effective in scenarios with smaller sample size and changing baseline hazard. Refitting performance depended on sample size and produced abrupt changes in hazard ratio estimates between periods.

Reinterpretation of Hepatopancreaticobiliary Imaging Exams: Assessment of Clinical Impact, Peer Learning, and Physician Satisfaction

To assess the impact on clinical management, potential for peer learning, and referring physician satisfaction with subspecialist reinterpretations of hepatopancreaticobiliary (HPB) imaging examinations. HPB CTs and MRIs from outside hospitals were reinterpreted by two subspecialty radiologists between March 2021 and August 2022. Reinterpretation reports were mailed to radiologists that issued primary reports. The electronic record was reviewed to assess for changes in clinical management based on the reinterpretations (yes/no/unavailable). To assess the potential for peer learning, a survey using a 5-point Likert scale was sent to radiologists who issued primary reports. A separate survey was sent to referring physicians to assess satisfaction with reinterpretations. Two hundred fifty imaging examinations (122 CT, 128 MRI) were reinterpreted at the request of 19 referring physicians. Ninety-sixradiologists issued primary reports. RADPEER scores 1-3 were assigned to 131/250 (52%), 86/250 (34%), and 33/250 (13%) examinations, respectively. Of 213 reinterpretations with adequate records for assessment, 75/213 (35%) were associated with a change in management; of these, 71/75 (95%) were classified as RADPEER 2 or 3. Most radiologists agreed or strongly agreed with the following: prefer to receive reinterpretations (34/36, 94%); reinterpretations changed practice of reporting HPB imaging examinations (23/36, 64%); and reinterpretations offer opportunities for peer learning (34/36, 94%). Referring physicians agreed or strongly agreed (7/7, 100%) that reinterpretations are valuable and often change or clarify management of patients with complex HPB disease,and offeran opportunity for peer learning. Radiologists and referring physicians strongly agree that HPB imaging reinterpretations help support peer learning and patient management, respectively.

Quality of Life in Childhood Immune Thrombocytopenia: Revision of the Kids' ITP Tools (KIT)

Introduction New treatment approaches have emerged for pediatric ITP over the years, potentially impacting the health-related quality of life (HRQoL) of affected individuals. The Kids' ITP Tools (KIT) (Child self-report/Parent proxy-report and Parent impact-report) have gained international attention as valid tools for monitoring HRQoL in children with ITP and the impact on their parents. The questionnaires were recently updated to reflect changes in clinical management. However, it has also become common practice to evaluate the impact of new therapies using domain scales of QOL (i.e., sub-categories), which are not yet available for the KIT. Thus, the primary objective of this study was to establish domain scales for the KIT 2.0 that accurately quantify and identify specific aspects of HRQoL that are impacted in children with ITP and their parents. Methods The study was conducted in two sequential phases. Phase 1 involved ITP experts identifying key conceptual domains for the KIT questionnaires based on their clinical experiences. An online survey (“card sort survey”) was distributed, and experts sorted the current KIT 2.0 questions into domains, with domain headings suggested as well. Phase 2 involved a statistical approach (i.e., exploratory factor analysis (EFA)) to yield models with different number of domains. Data from children with ITP and their parents was utilized to develop the models, and the data was specifically from three previous international multicentre studies: ITP Consortium of North America (ICON1 study), UK Children's Hospital (UK ITP Paediatric Registry), and the Children's Hospital of Eastern Ontario (KIT international validation). Results In Phase 1, 24 experts completed the Child self-report card-sort survey, while 12 experts completed the Parent impact survey. There were two models that were derived for the Child Self-Report, with one having three domain scales and the other with four domain scales. The Parent Impact resulted in only one model that had three domain scales. In Phase 2, exploratory factor analysis (EFA) resulted in three models for each of the three questionnaires (Table 1), with the final models selected from the EFA and based on clinical interpretability. The four-domain model was selected for the Child Self-Report. The model had a higher Tucker Lewis Index (TLI) score and cumulative percentage of variance compared to the three-domain model. Though the cumulative percentage of variance was higher for the six-domain model, the model had two domains that each contained only two questions, which is not ideal for face validity. The final domain headings for the Child self-report were derived from the expert card sort survey: ITP Uncertainty; General symptoms; ITP challenges/disruptions; and Loss of control. The four-domain model was also selected for the Parent proxy-report on the basis of the same factors as the Child self-report. Likewise, the four-factor model had higher TLI score and relatively lower root mean square error of approximation (RMSEA) compared to the three-factor. The six-factor model had an ideal RMSEA, but contained one domain that had only two questions. The final domain headings are the same as the Child self-report as the context of the questions are the same. The four-domain model was selected for the Parent impact-report. Though both the four- and six-factor models contained two domains with only two questions each, the two-factor model was not ideal clinically as the questions within each of the two domains were not all similar. The headings were also derived from the expert card-sort: ITP Uncertainty; Treatment; Functional well-being; and Activities. Conclusion The revised KIT 2.0 aims to comprehensively summarize health-related quality of life in pediatric patients with ITP and their parents. The introduction of a domain structure derived from expert- and patient-data to the KIT will enable identification of specific aspects of QOL that are affected, which is imperative given the introduction of novel pharmaceutical agents in ITP treatment.