Common Indication For Referral Research Articles

OGC SO02 - Analysis of routine upper gastrointestinal endoscopy referrals and outcomes in a single tertiary service

Abstract Background Routine (category 3/4) upper gastrointestinal endoscopies (UGIE) constitute a significant proportion of endoscopy workload in the National Health Service. Referrals are varied and there are opportunities for service improvement to reduce clinician burden and improve patient outcomes. This is of particular relevance to the early detection and prevention of cancer. This work aimed to analyse routine UGIE referrals and subsequent endoscopies in a large tertiary service to identify quality improvement opportunities within the health board. Method Referral indications for all males over 50 years awaiting routine UGIE in the health board on 02/03/2023 were reviewed. Referrals were categorised into 7 groups based on primary presentation and indication for UGIE; “Liver/variceal”, “Gastric”, “Oesophageal”, “Anaemia”, “Dysphagia”, “Tissue transglutaminase (TTG) positive” or “Other”. Data on findings, biopsy, and follow-up were gathered where UGIE was subsequently performed. To analyse routine cases only, patients referred for anaemia or dysphagia were excluded from final analysis. Results 471 records were reviewed and 332 patients included in final analysis; 210 had undergone UGIE at assessment point (3 records unavailable), with 99 waiting and 23 died/did not attend/declined. The most common referral indications were “Gastric” (41.6%), “Liver” (29.2%), and “Oesophageal” (21.4%) (n=207). 84 were excluded due to anaemia/dysphagia. At UGIE, 6.3% identified Barrett's oesophagus/malignancy across all groups with 1 case of new malignancy. 80.2% received medical/conservative management following their scope. Conclusion While pathology was identified at routine UGIE, a large number of procedures were required to identify this and there was no Barrett's oesophagus rich group. We have identified opportunities for improvement in the delivery of routine UGIE service in the health board which may reflect nationally. These include altered vetting practices and potential UGIE-saving procedures including cytosponge.

OGC SO11 - Impact Evaluation of Endoscopic Mucosal Resection in the Foregut in a Tertiary Centre in the United Kingdom (UK)

Abstract Background Endoscopic mucosal resection (EMR) has emerged as a crucial technique for managing early-stage lesions in the oesophagus and stomach, encompassing precancerous and cancerous conditions.1 With fewer complications and excellent 5-year survival rates, EMR has shown potential as a less-invasive alternative to surgical resections.1 EMR achieves higher accuracy with its ability to obtain more profound and better quality tissue samples compared to conventional biopsies, which facilitates multidisciplinary team (MDT) discussions regarding treatment decisions.1 This study aims to evaluate the impact of EMR performed in an Oesophago-Gastric Cancer tertiary centre in the UK. Method This is a retrospective service evaluation of patients who underwent EMR from March 2021 to March 2024. A sample size of 73 EM (n=73) is identified. Data were collected from medical and endoscopic records, which includes patient’s demographics, American Society of Anaesthesiologists (ASA) grade, EMR indication, histology report and MDT outcome. EMRs performed were categorised into oesophageal, gastric and duodenal. Three main referral indications were identified; ‘polyp’, ‘dysplastic nodule in Barrett’s oesophagus’ and ‘possible early malignancy’. MDT outcomes were analysed thematically. Results Of the seventy-three patients identified, 78% is male and mean age at 71 years. Most patients (81%) are classified as ASA Grade 2. Polyp is identified in 37 patients (51%), making up the most common referral indication. 49% of the EMR were gastric, with remaining being oesophageal (41%) and duodenal (11%). 26% of histology results showed benign disease, 40% dysplastic disease, and 34% malignant. From histology reports, 47% of the EMRs achieved complete clearance margins. 28 patients (38%) were discharged with no further interventions and 12 patients (16%) received repeat EMR. 4 main themes were identified from MDT outcomes, with 43.8% patients needing surveillance endoscopy, 16.7% patients recommended for surgical intervention and repeated EMR each. Conclusion EMR has shown to be effective as a reference for further treatment decisions, especially for MDT discussions. It has been proven that EMR can be therapeutic in providing complete resection, particularly for benign and early dysplastic diseases.

Abstract 4122486: Multicenter Study of Primary Fetal Cardiomyopathy: Clinical Outcomes And Genetic Etiologies, A Fetal Heart Society Research Collaborative Study

Background: Fetal cardiomyopathy (FCM) affects 8 per 100,000 live births, often with unknown etiology. Progress in fetal cardiac screening, genetic testing and management may have impacted historically poor outcomes. Aims: We sought to investigate genetic associations and clinical outcomes of FCM in the current era. Methods: This was a retrospective Fetal Heart Society Research Collaborative cohort study of FCM cases diagnosed from January 2017-December 2021 in 39 centers. Cases of fetal myocardial disease attributable to maternal diabetes, structural heart disease, arrhythmia or extra-cardiac conditions were excluded. Data including outcomes to 1 year after birth were collected. Significance of genetic testing results and FCM subtype were classified by each center. Results: There were 138 FCM cases diagnosed at a median gestational age of 27 +4 weeks (range 13-39 weeks). Suspected fetal heart disease (41%, 56/138) was the most common referral indication. There was a known family history of CM in 19% (26/138). FCM phenotypes included 38% (52/138) dilated, 24% (33/138) hypertrophic, 17% (24/138) non-compacted, 10% (14/138) mixed, 5% (7/138) restrictive, 3% (4/138) ventricular aneurysm, 3% (4/138) unspecified. Hydrops was present at diagnosis in 15% (20/138) and by delivery or at fetal demise in 26% (36/138). Of 128 continued pregnancies, 7% (9/128) had a fetal demise, 92% (118/128) a live birth and one was lost to follow-up. Among live births, 10% (12/118) received only palliative care. Of 106 actively treated, 75% (80/106) survived to 1 year; 7% (7/106) required ECMO, and 22% (23/106) were listed for transplant with 18 of these successfully transplanted. Of the cohort, a total of 80% (110/138) had genetic testing (including 30 with invasive prenatal testing), with 38% (52/138) having a confirmed genetic etiology and 28% (38/138) with a variant of uncertain significance (VUS) (Figure 1). Transplant-free survival to 1 year was similar for those with and without a genetic diagnosis (40%,21/52 vs 47%,40/86, p=0.48). Conclusion: Outcomes remain poor in FCM, with <50% 1-year survival overall. Confirmed genetic etiologies are now identified in nearly 40%, highlighting the importance of genetic testing.

Starting a surgical prehabilitation program: results from a pragmatic nonrandomized feasibility study.

We sought to assess the feasibility and estimate the effects on outcomes of a multimodal prehabilitation service implemented as an ancillary surgical service. We conducted a pragmatic, nonrandomized feasibility study of surgical prehabilitation. Patients were eligible if they were ≥ 18yr of age, fluent in English, and referred by a health professional for prehabilitation. Participants received an individualized program of preoperative exercise, nutrition, psychological, and/or smoking cessation support. The primary outcome was operational feasibility, including referral volume, enrolment rate, prehabilitation window, engagement, completion rate, and safety. Secondary outcomes included surgical complications, length of hospital stay, readmission, quality of life, and physical and mental health. Qualitative data related to intervention feasibility and acceptability. We compared intervention participants with patients who were referred for, but declined, prehabilitation. One hundred and sixteen patients were referred for prehabilitation. The mean age of referred patients was 71yr and 55% were male. Over 90% of referrals were from surgical oncology, and the most common indication for referral was frailty (46%). Of the 116 referred patients, 83 consented to participate in the study. Patient-reported and objectively measured outcomes improved by a clinically important margin from baseline to presurgery, and returned to presurgery levels by 90days postoperatively. Qualitative findings suggest that the prehabilitation intervention was well received. Multimodal surgical prehabilitation is feasible as an integrated clinical service and may be effective for improving physical and psychological outcomes. Further evaluations of clinically integrated prehabilitation programs in Canada are needed to confirm these findings.

777. COMBINED OESOPHAGEAL AND AIRWAY STENTING FOR MALIGNANT OESOPHAGEAL STRICTURES: THE UK’S LARGEST TERTIARY CENTRE EXPERIENCE AND DEVELOPMENT OF A NOVEL ALGORITHM

Abstract Background Malignant oesophageal strictures can cause airway compromise and fistula formation. Combined oesophageal and airway stenting is a potential treatment yet no guidelines exist. This study aims to describe the outcomes of same-session oesophageal and airway endoscopic stenting for malignant strictures and propose an algorithm for intervention. Methods A retrospective study on patients undergoing same-session gastroenterology (GI) and respiratory endoscopy at University College London Hospital, 2019-2023. All procedures were with anaesthetic-led propofol sedation. Endoscopic decision making was based on pre-procedure multidisciplinary team meeting (MDM) and intra-procedure clinical assessment. Data collected included malignancy type, luminal narrowing, complications, and mortality. Results 26 patients were identified. Mean age was 63 years. Cancer type was oesophageal (81%) or lung (19%). The most common referral indication was dysphagia (42%); airway compromise was often seen on imaging (65%). Stent insertion was oesophageal only (35%), airway only (19%) and dual (27%). Airway stenting was common (80%) if airway stenosis was >50%. No airway stenting occurred if stenosis was <50%. After oesophageal stenting, repeat bronchoscopy showed increased airway stenosis in 4 patients (25%). The only intraoperative complication was one oesophageal perforation. New tracheooesophageal fistula was the most common post-intervention complication (15%). Median time from malignancy diagnosis to death was 7.9 weeks. Conclusion We present the first algorithm (Figure 1) for endoscopic stenting in patients with malignant oesophageal stricture and airway involvement. We suggest upper GI and respiratory MDM to plan same-session endoscopy with decision-making framed by patient-centred goals given their poor prognosis.

262. EOSINOPHILIC ESOPHAGITIS: A SEVEN YEAR ANALYSIS OF EPIDEMIOLOGY IN A UNITED KINGDOM COUNTY

Abstract Background Eosinophilic Esophagitis (EoE) is growing in incidence internationally. It is an immune-mediated disease that is characterised by esophageal mucosal eosinophilia and esophageal dysfunction. Awareness of EoE is also crucial for Esophagogastric surgeons as symptoms may mimic reflux disease or neoplasia, key considerations for an accurate differential diagnosis. Presently, there are no incidence estimates of EoE in the adult population in the UK. This study seeks to establish a cohort of EoE patients in Norfolk, a county in the East of England region, and to describe the incidence, characteristics, and diagnostic features of affected patients in both the adult and paediatric populations. Methods A retrospective analysis was performed of a prospectively maintained pathology database servicing a population of 761,000 persons in Norfolk. All newly diagnosed cases of EoE across a seven-year period between January 2017 and December 2023 were identified. Patients included for analysis had a histological diagnosis of EoE with >15 eosinophils/hpf and symptoms of oesophageal dysfunction. Patient electronic health care records were reviewed for histology reports, endoscopic findings, and clinical history. The primary outcome was incidence of EoE within the county. Secondary outcomes assessed included: patient characteristics; allergy and atopy history; endoscopic features, biopsy protocol and referral indication. Results 187 (median age 43 (4-85) years, Male: Female (126:61)) new cases of EoE were identified, of whom eight were in the paediatric age group of ≤16 years. The average annual incidence of EoE was 4.29 [95% CI 2.92, 5.66] and 0.89 [95% CI 0, 1.39] per 100,000 person/years in adult and paediatric groups respectively, with a significantly higher incidence in adults (RR 4.86 (95% CI [2.39 – 9.85] P<0.005) (Figure 1). The most common referral indications for endoscopy were dysphagia (80.7%) and food bolus obstruction episodes (25.1%). The most common endoscopic feature of EoE was circular rings (49.2%). Conclusion This is the first study reporting incidence of EoE in the UK adult population. There was a significantly greater incidence of EoE in adults compared to the paediatric population. However, there was no significant change in incidence of EoE in either group over the study period. Incidence estimates identified are similar to those reported in other European populations. Importantly 18.2% of patients had normal appearance of oesophagus on endoscopy, which reinforces the need to take oesophageal biopsies where there is clinical suspicion. Ideally, prospective registry data is needed for a comprehensive characterisation of incidence and prevalence of EoE.

Description and outcomes of a staff-assisted peritoneal dialysis program in the United States.

Staff-assisted peritoneal dialysis (PD) can help overcome barriers to self-care but is not yet available in the United States (US). We developed and implemented a staff-assisted PD program that fits within current regulatory and cost restraints in the US healthcare environment. Patient care technicians (PCTs) were trained on PD procedures and troubleshooting common problems. The program expanded from two centers in August 2020 to sixteen by October 2022. We described the logistic elements of program delivery, and patient and treatment outcomes for patients discharged by end of April 2023, with a cohort follow up until October 2023. A total of 121 patients were referred to the program. The most common indications for referral were physical function limitations, cognitive impairment, and psychosocial challenges. Staff assistance was provided for 73 patients. Mean age was 72 (standard deviation 14) years. A total of 604 visits were delivered, with a median 5 (interquartile range [IQR] 3-10, range: 1-49) visits per patient. Median duration of assistance was 8 (IQR: 2-21, range: 1-84) days. Assistance was most frequently needed for PD treatment setup and for observing and directing the technique. No peritonitis events or exit-site infections were reported. Sixty-eight patients (93%) were discharged on PD without staff assistance. The 6- and 12-month survival of PD without assistance was 71% and 57%, respectively. Staff-assisted PD for limited time periods is operationally feasible with PCTs in the US and can support transitioning and maintaining patients on PD.ClinicalTrials.gov Identifier: NCT04319185.

Adherence to clinical practice guidelines for pulmonary valve intervention after tetralogy of Fallot repair: A nationwide cohort study

ObjectivesTo determine guideline adherence pertaining to pulmonary valve replacement (PVR) referral after tetralogy of Fallot (TOF) repair. MethodsChildren and adults with cardiovascular magnetic resonance imaging scans and at least moderate pulmonary regurgitation were prospectively enrolled in the Comprehensive Outcomes Registry Late After TOF Repair (CORRELATE). Individuals with previous PVR were excluded. Patients were classified according to presence (+) versus absence (−) of PVR and presence (+) versus absence (−) of contemporaneous guideline satisfaction. A validated score (specific activity scale [SAS]) classified adult symptom status. ResultsIn total, 498 participants (57% male, mean age 32 ± 14 years) were enrolled from 14 Canadian centers (2013-2020). Mean follow-up was 3.8 ± 1.8 years. Guideline criteria for PVR were satisfied for the majority (n = 422/498, 85%), although referral for PVR occurred only in a minority (n = 167/498, 34%). At PVR referral, most were asymptomatic (75% in SAS class 1). One participant (0.6%) received PVR without meeting criteria (PVR+/indication–). The remainder (n = 75/498, 15%) did not meet criteria for and did not receive PVR (PVR–/indication–). Abnormal cardiovascular imaging was the most commonly cited indication for PVR (n = 61/123, 50%). The SAS class and ratio of right to left end-diastolic volumes were independent predictors of PVR in a multivariable analysis (hazard ratio, 3.33; 95% confidence interval, 1.92-5.8, P < .0001; hazard ratio, 2.78; 95% confidence interval, 2.18-3.55, P < .0001). ConclusionsAlthough a majority of patients met guideline criteria for PVR, only a minority were referred for intervention. Abnormal cardiovascular imaging was the most common indication for referral. Further research will be necessary to establish the longer-term clinical impact of varying PVR referral strategies.

Practice Patterns for Addressing Developmental-Behavioral Concerns in Sickle Cell Specialty Care.

Children with sickle cell disease (SCD) are at elevated risk for neurodevelopmental and behavioral disorders. This report describes developmental-behavioral practice patterns among sites who were part of the Dissemination and Implementation of Stroke Prevention Looking at the Care Environment (DISPLACE) consortium in the context of current guidelines for addressing these concerns. An internal survey was developed for the Principal Investigators of the DISPLACE study to identify developmental-behavioral clinical practices across the 28-site consortium, including methods for identification, referral practices, access to psychologists, and barriers to services. Descriptive data were pulled from the survey to describe practice patterns. Most sites used informal methods to detect developmental-behavioral concerns, though over 1/3 of sites were using a structured protocol. The most common referral indications for further developmental and neuropsychological evaluation were parent, provider, or school concerns or stroke. Evaluations were predominantly completed by pediatric neuropsychologists and pediatric psychologists. Despite most sites reporting access to a psychologist within the SCD clinic, sites also reported long waitlists and difficulty accessing providers for evaluation and treatment services. Insurance difficulties were also a common barrier. A range of additional barriers were reported at the patient, provider, organizational, and policy/socio-environmental levels. Many sites in the DISPLACE consortium were adhering to existing care guidelines for pediatric SCD; however, there was also wide variation in practices for which guidelines are absent or unclear. Additional work is needed to inform guidelines, to specify the role of psychology within specialty SCD care, and to overcome barriers to care. Optimal developmental-behavioral care for children with SCD involves collaboration among specialty care providers and pediatric psychologists; however, these efforts may be hampered by dispersed or unclear guidelines and several barriers to care. Future studies and guidelines have the potential to improve care by providing clear, consistent, and unified care recommendations specific to psychologists and related care professionals who are supporting children with SCD.

Abstract A50: Distinguishing Mosaic Li Fraumeni Syndrome, Clonal Hematopoiesis and Incidental Myeloid Neoplasms in Patients with Solid Tumors with Pathogenic TP53 Mutations Identified by Germline Testing or Cell-Free Circulating DNA Sequencing

Abstract The incorporation of panel-based germline genetic testing for assessment of pathogenic or likely pathogenic variants associated with increased risk of breast, ovarian, prostatic and pancreatic cancer in NCCN guidelines and wide adoption of cell-free circulating DNA sequencing (liquid biopsy) for patients with advanced solid tumors has increased the identification of pathogenic TP53 variants in blood of patients with solid tumors. The variant allelic frequency (VAF) of the pathogenic variant is often used to help infer the compartment of origin (germline vs somatic) with near heterozygous (~50%) VAF favoring germline; however, when VAF is low (sub heterozygous) potential considerations include mosaic Li Fraumeni syndrome, clonal hematopoiesis, or incidental myeloid neoplasms, and determining the origin of the TP53 mutation can be a challenge with important surveillance and treatment implications. We describe a cohort of patients with solid tumors or hematologic malignancies in whom pathogenic or likely pathogenic TP53 variants of uncertain origin were identified by clinical genetic testing of peripheral blood, next generation sequencing (NGS) using an 81 gene hematologic malignancy-based panel, or cell-free DNA sequencing/liquid biopsy. In a subset of patients for whom solid tumor, adjacent normal tissue and/or bone marrow (BM) was available, immunohistochemistry for p53 protein was performed. Patients (n= 17) included 11 (61%) women and 7 (39%) men with a median age of 54 years (range 8-7) at initial cancer diagnosis, with 17 unique TP53 variants with a median VAF of 16% (range, 2-50%). The most common indication for referral for additional investigation of the TP53 origin was sub-heterozygous VAF on germline testing of blood (8/47%) or saliva (1/6%); TP53 variant identified in plasma when the concurrent solid tumor was TP53 wild-type (3/18%) followed by presence of a pathogenic TP53 variant in remission BM of patients with history of hematologic malignancies (4/24%). Additional germline testing of skin fibroblasts and/or BM examination was performed in in 9 (53%) and 8 (47%) patients, respectively. p53 IHC was performed on 3 BM biopsies and 2 solid tumor tissues. A multimodality/multidisciplinary interpretation of these results allowed appropriate classification of the TP53 variants in 12/18 patients (67%). These included Li Fraumeni syndrome (5/12; 42%); clonal hematopoiesis (5/12; 42%); donor-derived clonal hematopoiesis (1/12;8%) and therapy-related myelodysplastic syndrome (1/12; 8%) patients. Appropriate awareness and distinction of clonal hematopoiesis and potential myeloid neoplasms from mosaic germline TP53 in the setting of subheterozygous VAF identified on peripheral blood or bone marrow analyses can be challenging. Multimodality testing and a multidisciplinary approach for accurate interpretation is required. Immunohistochemical staining for p53 can be useful in making this distinction in a subset of patients. Citation Format: Sanam Loghavi, Yoheved Gerstein, Mark J Routbort, Keyur P Patel, Koichi Takahashi, Molly Daniels, Julie Moskowitz, Danielle E Hammond, Kelly Chien, L. Jeffrey Medeiros, Farhad Ravandi, Hagop M Kantarjian, Guillermo Garcia-Manero, Banu Arun, Joseph D Khoury, Courtney D DiNardo. Distinguishing Mosaic Li Fraumeni Syndrome, Clonal Hematopoiesis and Incidental Myeloid Neoplasms in Patients with Solid Tumors with Pathogenic TP53 Mutations Identified by Germline Testing or Cell-Free Circulating DNA Sequencing [abstract]. In: Proceedings of the AACR Special Conference: Acute Myeloid Leukemia and Myelodysplastic Syndrome; 2023 Jan 23-25; Austin, TX. Philadelphia (PA): AACR; Blood Cancer Discov 2023;4(3_Suppl):Abstract nr A50.

Palliative medicine referral and end-of-life interventions among minority patients with advanced or metastatic gynecologic cancer (433)

Palliative medicine referral and end-of-life interventions among minority patients with advanced or metastatic gynecologic cancer (433)

Referring Provider Opinions of Pediatric Cardiology Evaluations Performed by Nurse Practitioners.

In the setting of physician shortages, nurse practitioner (NP) roles have evolved, with increasing independence across most healthcare settings. We sought to characterize referring clinician perceptions of NP-performed outpatient pediatric cardiology consultations. We electronically distributed to pediatric and family medicine physicians and NPs in Arkansas our 11-item survey assessing the acceptability of pediatric cardiology consultations being completed by an NP under varying circumstances. Circumstances included seven common referral indications, and the scale offered five answer choices ranging from "definitely unacceptable" to "definitely acceptable". A total of 292 of 1756 (16.6% response rate) referring clinicians responded to the survey. Overall, 57% of responses indicated that NP-completed pediatric cardiology evaluations were either definitely or probably unacceptable. Acceptability was varied by referral indication and referring clinician characteristics. Unacceptability of NP-completed pediatric cardiology evaluations was greatest among family medicine physicians (81%), pediatricians (66%), and clinicians working in solo or two-physician practices (77%) or community hospitals/clinics (71%). If NP evaluation of a murmur included required review with a cardiologist, the unacceptability rate dropped from 50 to 24% (p < 0.0001). Unacceptability was higher in physicians who do not work with NPs (69%) compared to those who do (60%) (pp < 0.0001). Many referring physicians were willing to send patients ≥ 100 miles to ensure evaluation by a pediatric cardiologist. Most referring physicians find pediatric cardiology evaluations performed by NPs to be unacceptable. Requisite review with a cardiologist improved acceptability of NP evaluations. Many referring physicians would send patients much farther to guarantee evaluation by a cardiologist.

Investigating factors that influence genetic counselors' decisions to referpatients to mental health providers.

Genetic counselors (GC) serve patients who are often in distress at the time of their consultation. GC competency includes providing short-term, client-centered counseling, while using community resources, such as mental health providers (MHPs), for psychosocial support. The purpose of this study was to assess the mental health referral practices of GCs; specifically, the rate of referrals, factors influencing a GC's decision to refer, and barriers to referrals. GCs working in direct patient care for at least one year were recruited to take a novel 27 question survey created based on the results of a previous qualitative study. A link to the web-based survey was distributed through the National Society of Genetic Counselors Student Research Program and American Board of Genetic Counselors by email. A total of 144 individuals opened the survey for an estimated response rate of 3%. A majority of respondents (54.3%) reported they assess a patient's need for a mental health referral at least half of the time. The mean number of referrals made in the past 12months was 5.13. After post-hoc analyses, there were no differences in referral rates between specialties. Common referral indications included patient history of mental illness, distress about having a genetic condition, and limited social support. Common barriers to referral were financial or insurance related, patient receptiveness, and the patient not perceiving a benefit. GCs felt that providing psychosocial support is within their scope of practice, but that MHPs are better equipped to manage long-term needs and those related to a mental health condition. This study provides insight into how GCs decide when they can manage patient distress, circumstances that prompt a referral to MHPs, and barriers. Recognizing common referral indications and barriers may lead to better strategies for connecting patients with such services.

EP155: Genetic investigation of idiopathic short stature in the endocrinology practice: The Mayo Clinic experience

Childhood short stature is a common indication for referral in endocrinology. The differential diagnosis is broad including endocrine disorders, systemic disorders, and genetic disorders. Many genetic disorders are associated with growth disturbance including non-syndromic growth hormone disorders, syndromic short stature, and skeletal dysplasias. A subset of children are classified as having idiopathic short stature (ISS), which could be further subdivided into familial or non-familial short stature. The lack of cardinal features in ISS often prevents genetic evaluation and diagnosis of non-syndromic genetic short stature. However, emerging data indicates the identification of a genetic disorder in 25-40% of individuals with ISS when utilizing copy number variant analysis, targeted gene panels and exome sequencing. Genetic testing is becoming an essential component of the diagnostic evaluation and treatment of patients in traditionally underutilized clinical departments. The Pediatric Endocrinology department and Center for Individualized Medicine (CIM) at Mayo Clinic collaborated to develop a genetic testing service for pediatric ISS to explore the yield of genetic diagnosis and impact to medical management utilizing a novel genetic counseling model called the Genetic Testing and Counseling (GTAC) unit consisting of genetic counselors, genetic counselor assistants, genetic nurses, and a medical geneticist. Through GTAC, patients receive appropriate counseling, and test facilitation through partnership between the genetic counseling team and referring specialty provider. Eligibility for a referral to the GTAC service included children with proportionate short stature greater than 2 SD below mean for age and sex, in the absence of an identifiable causative etiology. Children with skeletal dysplasias and syndromic short stature were not included in this service and underwent genetic evaluation through traditional referrals to the Department of Clinical Genomics. Through the GTAC service, pre-test genetic counseling appointments range from 15-30 minutes focusing on pre-selected genetic tests. For ISS, a custom exome-based multi-gene panel was curated and created to include 53 genes associated with non-syndromic short stature or disorders with mild or variable expressivity such as some RAS-opathies. Chromosomal microarray (CMA) was also ordered as a standard first tier test. Genetic test results were reviewed by the endocrinologist and the GTAC Genomics team. Results were returned to the patient via post-test genetic counseling, and medical management and follow-up was facilitated by the endocrinologist. From April 2021 to November 2021, there have been 13 referrals to the GTAC service, and all 13 (100%) patients elected to proceed with genetic testing. Multi-gene custom panel and CMA were completed for 11 patients. CMA, as a standalone test, was completed for one patient because a diagnosis was obtained with this initial test. Testing is pending for the remaining 2 patients. The multi-gene panel revealed a likely pathogenic or pathogenic causative variant in 5/10 patients tested (ACAN, IGF1, IGF1R, and SHOX) and CMA revealed a pathogenic causative copy number variant resulting in deletion of the SHOX gene in 1/5 patients. Together, the diagnostic yield through this testing approach is 54%. Therapeutic options were available for all 6 (100%) solved cases. Three of the 6 (50%) diagnosed cases had family histories consistent with the finding and included reports of one or more close relatives (first or second degree) with associated features (eg, short stature, mesomelia, forearm deformity). The molecular finding was able to be confirmed in affected parents of 2 of these 3 cases; parental testing of the third is pending. Parental samples were submitted to aid in the interpretation of results in 6/11 cases; parents were not included in 2/11 cases and the patient was adopted in 3/11 cases. Genetic counseling and testing are important components in the overall evaluation of idiopathic short stature; however, genetic counseling expertise embedded in the endocrinology practice is rare. The collaboration between GTAC and the specialty area partners has demonstrated immediate and ongoing value to patients and providers. This partnership highlights the significant diagnostic genetic yield and impact to patient management in unexplained short stature. Genetic testing is underutilized and should be considered in pediatric patients with not only ISS but also cases of familial short stature. A genetic diagnosis in children with short stature is instrumental for informing prognosis, the potential to inform treatment decisions surrounding use of growth hormone or insulin-like growth factor 1 therapy and clarifying inheritance and recurrence risks.

Developmental Dysplasia of the Hip: Prevalence and Correlation with Other Diagnoses in Physiotherapy Practice-A 5-Year Retrospective Review.

(1) Background: The objective of this study was to assess the prevalence of Developmental Dysplasia of the Hip (DDH) as a primary or secondary diagnosis during physiotherapy practice. No other studies have investigated the prevalence and associations of DDH within the practice of pediatric rehabilitation. (2) Methods: This retrospective review was performed on 12,225 physiotherapy referrals to the King Abdullah Specialized Children’s Hospital (KASCH), Riyadh, Kingdom of Saudi Arabia, from May 2016 to October 2021. Only DDH referrals for conservative treatment were included in the study. The plan for brace treatment was carried out by the pediatric orthopedics clinic in KASCH. The diagnostic methods were either a pelvic radiograph or ultrasound, depending on the participant’s age. DDH is considered one of the most common secondary complications for children with other medical diagnoses. (3) Results: The most common indication for referral was neurological diagnosis (44%), followed by orthopedic (28%), genetic (19%), cardiac (5%), ophthalmologic (3%), dermatologic (1%) and rheumatologic (0.5%) diagnoses. (4) Conclusion: The prevalence of DDH among all referrals in this study was 6%. In physiotherapy practice, neurologic, genetic, and orthopedic primary or secondary diagnoses were the most prevalent when DDH referrals were investigated. A relatively high prevalence of DDH in the pediatric rehabilitation clinic at KASCH in Riyadh was reported in this study.

Assessing genetic counselors' graduate school education and training in congenital heart defects.

Genetic counselors are one of the many providers involved in caring for patients with congenital heart defects (CHDs); however, little is known about the cardiovascular genetics training they receive by their graduate programs. To explore the recalled education experiences regarding CHDs by practicing genetic counselors, we surveyed graduates of programs primarily accredited by the American Council on Genetic Counseling (ACGC) about their graduate training in this area, the depth of CHD-specific education they received, and whether CHDs are a substantial referral indication in their current practice. Genetic counselors were recruited from the National Society of Genetic Counselors and Twitter (n=112), and participants reflecting multiple specialties and 35 graduate programs completed an online survey which included questions about fieldwork placements and lectures in cardiovascular genetics, exposure to classification schemes regarding cardiac embryology, and education in counseling strategies for CHDs and CHD-related topics during their graduate training. When asked whether CHDs are a substantial referral indication seen in their current practice, 55% (62/112) responded yes. Most participants (79%, 88/112) recalled receiving some education about CHDs, but 91% (80/88) reported receiving little to no education regarding embryologic classification of CHDs and how to apply classification schemes to their counseling. Both participating prenatal and pediatric GCs reported that CHDs can be a common referral indication, yet they reported receiving limited education on teratogens associated with CHDs, family screening recommendations, and recurrence risk counseling for CHDs. Based on participant responses, the majority of respondents reported receiving sufficient education on syndromes with CHDs which can be beneficial in specialties such as pediatrics. This exploratory study provides insight into opportunities to further support genetic counseling educational opportunities for CHDs. These findings suggest genetic counseling graduate programs could consider implementing education on CHD counseling strategies as a standardized component of the curriculum and that practicing genetic counselors could benefit from educational opportunities and resources with updated information on this topic.

Do Family History Questions Improve the Predictive Value of a Standardized Pediatric Bleeding Assessment Tool?

▪Bleeding assessment tools to standardize and interpret bleeding history have variable reported sensitivity and specificity to identify patients with mild bleeding disorders (MBD), particularly in subspecialty referral cohorts or younger patients with fewer hemostatic challenges. Here we review the predictive value of the International Society of Thrombosis and Haemostasis (ISTH) bleeding assessment tool, BAT, with or without the addition of 2 family history questions (FHQ), the BAT+, in our clinical cohort. Our hypothesis was that the addition of FHQ would improve the predictive value of the BAT for presence of a MBD in newly referred pediatric hematology clinic patients, particularly those < 8 yr. After 4 quality improvement cycles, a BAT flowsheet in the electronic medical record has been administered to new clinic patients referred to rule out MBD. The exploratory FHQ are added (BAT+), asking about the presence of a first degree relative with a bleeding disorder (yes = 1 point) or first- or second-degree relatives with any of a list of bleeding symptoms (yes = 1 point for each symptom). After IRB approval, electronic records from new clinic visits for “possible MBD” from 1/29/19 to 2/28/20 were retrospectively reviewed for clinical and demographic data, including scoring of the BAT/BAT+. Data are reported descriptively. Positive predictive values (PPV) and negative predictive values (NPV) were compared to assess the predictive power of dichotomized scores. The predictive power of continuous scores were assessed by comparing area under the curves (AUC) of receiver operating characteristics (ROC) curves for each questionnaire. To assess whether higher scores were predictive of multiple diagnoses, we estimated nested hurdle and Poisson regressions with robust standard errors, with the count of bleeding diagnoses as dependent variable and BAT/BAT+ scores as predictors. Over 13 months, in 313 new visits in patients ages 0-21 yr., 309 (98.7%) had BAT+ assessment and were evaluable. Common referral indications were abnormal lab results (48%), epistaxis (20%) and easy bruising (15%). Clinician-initiated documentation of screening for joint hypermobility by examination or history-taking occurred in 85 visits (28%), with 15 (5%) assigned a hypermobility diagnosis. At least 1 MBD was identified in 86 (28%) and 171 ( 55%) had MBD ruled out by the clinician. The average scores for BAT/BAT+ were 1.7/2.6 respectively for those judged by clinician not to have MBD, vs. 2.5/3.9 for 1 MBD diagnosis and 4/6.2 for 2 or more MBD. Using a threshold score of 3 for BAT as predictor of MBD in pediatrics, a threshold of 6 for the BAT+ was selected because its NPV for the whole group was close to that of the BAT for threshold of 3. For all patients and children <8 yr. the PPV of the BAT+ was higher than for the BAT, indicating better ability to predict MBD, for a comparable NPV. This was statistically significant (p=0.033) in the full sample and marginally so (p=0.064) among <8 yr. (Table 2). The AUC for the entire group were 0.597 (0.523-0.670) for the BAT, improving to 0.627 (0.555- 0.6) for the BAT+; however, for < 8 yr. the BAT AUC of 0.528 (0.396-0.660) vs. 0.559 (0.426-0.692) for BAT+ did not significantly differ. By Poisson regression analyses, higher scores on either the BAT or BAT+ predicted more diagnoses, with FHQ improving the goodness of fit (p=0.012) for the whole group (and similar but not statistically significant for < 8 yr.). Scores trended higher for platelet disorders and hypermobility than for low von Willebrand factor/disease or other factor deficiencies. We conclude that the BAT is helpful for standardizing bleeding history among clinicians and trainees and, with flowsheet format, can streamline documentation and sustain high utilization rates. While estimates suggest that FHQ improve predictive power of the BAT, a larger sample size is needed for confirmation. Threshold scores cutoffs based upon pubertal status and gender in < 21 year-olds may need to be lower than for older adults with additional hemostatic challenges. In the entire group and for <8 yr., the BAT under-performed compared to highest published estimates for PPV, NPV and AUC, as has been reported in recent, more rigorous literature, highlighting the complexity of evaluating young specialty referral populations for MBD. [Display omitted] DisclosuresTarango: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees.

The Diagnostic Yield of Fetal Echocardiography Indications in the Current Era

The aim of this study was to examine the diagnostic yield of current fetal echocardiography (FE) indications representing a recent era. FE reports of all pregnancies referred to two provincial FE programs from 2009 to 2018 were examined, identifying the indication for FE (14 categories), gestational age at referral, and whether there was no fetal heart disease (FHD), mild or possible FHD (e.g., simple ventricular septal defect, possible coarctation), or moderate or severe FHD. Over the study period, there were 19,310 unique FE referrals in Alberta (23.3±5.4weeks' gestation), including 1,907 (9.9%) with moderate or severe and 654 (3.4%) with mild or possible FHD. The most common referral indications included extracardiac pathology or markers (29.7%), maternal diabetes (18.3%), suspected FHD (17.7%), and family history of heart defects (17.7%). The highest yield for moderate or severe FHD was suspected FHD (41.1%; 95% CI, 39.4%-42.7%), followed by suspected or confirmed genetic disorder (15.4%; 95% CI, 12.6%-18.2%), twins or multiples (10.6%; 95% CI, 8.7%-12.5%), oligohydramnios (8.0%; 95% CI, 4.1%-11.9%), extracardiac pathology or markers (6.4%; 95% CI, 5.8%-7.1%), and heart not well seen (5.8%; 95% CI, 4.0%-7.6%). Lowest yields were observed for maternal diabetes (2.2%; 95% CI, 1.7%-2.7%) and family history of heart defects (1.7%; 95% CI, 1.3%-2.2%). Excluding suspected FHD, with two or more FE indications, all other indications demonstrated significant increases in yield of mild or possible (3.5% vs 1.9%, P<.001) and moderate or severe (7.2% vs 2.9%, P<.001) FHD. Suspected FHD provides the highest diagnostic yield of moderate or severe FHD. In contrast, maternal diabetes and family history of heart defects, among the most common referral indications, had diagnostic yields approaching general population risks. Even in the absence of suspected FHD, having two or more referral indications importantly increases the diagnostic yield of all other FE indications.

Preimplantation Genetic Testing for Kidney Disease-Related Genes: A Laboratory’s Experience

Introduction: Recent literature highlights the clinical utility of genetic testing for patients with kidney disease. Genetic testing provides significant benefits for reproductive risk counseling, including the option of in vitro fertilization with preimplantation genetic testing for monogenic disease (PGT-M). PGT-M allows for a significant reduction in risk for a pregnancy affected with the familial disease. We aim to summarize our experience with PGT-M for genes with kidney involvement as either a primary or secondary feature of the disease. Methods: All PGT-M tests performed by the reference laboratory between September 2010 and July 2020 were reviewed for clinical indication and cases for which the disease tested included a renal component. Each patient referred for PGT-M had an existing molecular genetic diagnosis themselves or in their family. Frequency of each condition, gene, inheritance pattern, and year over year increase in referral cases was analyzed. Results: In the study cohort, the most common disease targeted was autosomal dominant polycystic kidney disease, caused by pathogenic variants in the PKD1 or PKD2 genes, which accounted for 16.5% (64/389) of cases. The 5 most common referral indications accounted for 51.9% (202/389) of the cases. Autosomal recessive inheritance accounted for 52.0% (26/50) of conditions for which PGT-M was performed. The number of PGT-M tests performed for conditions that included either primary or secondary kidney disease increased from 5 cases in 2010 to 47 cases in the 2020 study period. Discussion/Conclusion: These data suggest that the pursuit of PGT-M by couples at risk for passing on conditions with a kidney component is common and has significantly increased since 2010. With this rising trend of patients undergoing PGT-M and the prerequisite of molecular genetic confirmation in the PGT-M process, this study underscores the importance of the reproductive component to a molecular genetic diagnosis for patients with kidney disease, especially as the accessibility of genetic testing and utilization by nephrologists grows.

Usefulness of cardiovascular magnetic resonance in asymptomatic and symptomatic patients with complete left bundle branch block

Abstract Funding Acknowledgements Type of funding sources: None. Background Complete left bundle branch block (LBBB) is a common indication for referral for cardiovascular magnetic resonance (CMR) imaging. Purpose The objective of this study was to evaluate asymptomatic and symptomatic patients (pts) with complete LBBB referred to our outpatient institution for a stress CMR examination, in order to identify the cause of this block whether ischemic or non ischemic. Methods We prospectively analysed CMR data of all pts with complete LBBB who were referred for stress CMR (1.5 Tesla) to our Centre de Diagnostic Radiologique de Carouge. All pts had a complete LBBB as defined by standard criteria and all had an echocardiogram. All pts underwent a stress CMR using either adenosine or dobutamine. Standard protocol consisted of: 1) assessment of myocardial function at rest; 2) pharmacological stress induced either by dobutamine or by adenosine; 3) assessment of myocardial scar and/or viability by delayed enhancement (DE) sequences. Results A total of 138 pts, 75 women and 63 men, mean age 67.8 ± 15.4 years, with complete LBBB were referred for stress CMR. Of the 138 pts, 59 (43%) were asymptomatic (group 1) and 69 (50%) were symptomatic (group 2). Mean ventricular ejection fraction (LVEF) was 58 ± 17% in group 1, and 52 ± 17% in group 2 (p &amp;lt; 0.05). In group 1, 15 pts (25%) had abnormal LVEF values between 35-48% (mean value 41 ± 16%), and in group 2, 28 pts (41%) had LVEF values between 16-48% (mean value 35 ± 11%; p &amp;lt; 0.03 when comparing group 1 to group 2 values). Septal dyskinesia was present in 17 group 1 pts (29%) and in 27 group 2 pts (39%; p &amp;lt; 0.05 when comparing group 1 to group 2 values)). Stress CMR data revealed ischemia in 3 group 1 (5%) and in 9 group 2 pts (13%; p &amp;lt; 0.04 when comparing group 1 to group 2 values). Finally, DE sequences showed myocardial infarction in 8 pts of both groups (13% vs 12%), intramyocardial DEwas seen in 1 group 1 (2%) patient and in 2 group 2 pts (3%). Conclusions Our study showed that symptomatic pts with complete LBBB had a significantly lower mean LVEF and a higher number of wall motion abnormalities, mainly LV septal dyskinesia. Of note, CMR detected a rather low percentage of ischemic or non ischemic causes as well in asymptomatic as in symptomatic pts with complete LBBB.