Approved Study Research Articles

PD03-08 SURGICAL AND FUNCTIONAL OUTCOMES OF BILATERAL SYNCHRONOUS ADRENALECTOMY FOR FUNCTIONAL TUMORS: A COHORT STUDY

You have accessJournal of UrologyCME1 Apr 2023PD03-08 SURGICAL AND FUNCTIONAL OUTCOMES OF BILATERAL SYNCHRONOUS ADRENALECTOMY FOR FUNCTIONAL TUMORS: A COHORT STUDY Keshav Agarwal, Rashmi Ramachandran, Nikhil Tandon, and Rajeev Kumar Keshav AgarwalKeshav Agarwal More articles by this author , Rashmi RamachandranRashmi Ramachandran More articles by this author , Nikhil TandonNikhil Tandon More articles by this author , and Rajeev KumarRajeev Kumar More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003220.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Bilateral synchronous adrenalectomy has the potential for significant surgical and functional morbidity. We reviewed our 15-year experience with bilateral synchronous adrenalectomy to assess safety, surgical outcomes, morbidity and impact on health-related quality of life. METHODS: In an IRB approved study, we reviewed our prospective database of patients who underwent bilateral synchronous adrenalectomy for functional tumours between April 2008 and August 2022. Demographic profile, metabolic and radiological parameters, operative details and complications were recorded. Follow-up was obtained either in-person or telephonically and analysed for resolution of symptoms, quality of life using the WHO-QoL BREF questionnaire and complications of chronic steroid intake. RESULTS: During the study period, 337 adrenalectomies were performed which were bilateral in 51 patients, 48 undergoing both surgeries synchronously. 33 of these 48 patients had bilateral pheochromocytomas and 15 had Cushing’s syndrome. Among patients with Cushing’s syndrome, three had life-threatening symptoms requiring urgent bilateral surgery. Clinical details are given in Table 1. 40 patients had transperitoneal laparoscopic surgery and 8 underwent open surgery (Table 2). There were two intraoperative and 7 post-operative complications. 43 patients were available for follow-up. All had resolution of symptoms, BMI changes, and only two patients continued to receive one antihypertensive medication. Episodes of steroid deficiency occurred in 7 patients while steroid excess occurred in 3 patients. Quality of life was satisfactory in all patients in all domains. CONCLUSIONS: Bilateral synchronous adrenalectomy is safe and feasible in patients with functional adrenal tumors. It leads to symptom resolution with amelioration of hypertension and BMI changes with satisfactory overall quality of life. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e77 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Keshav Agarwal More articles by this author Rashmi Ramachandran More articles by this author Nikhil Tandon More articles by this author Rajeev Kumar More articles by this author Expand All Advertisement PDF downloadLoading ...

768 The Device for Intraventricular Entry (DIVE) Guide: A Novel Solution to a Perpetual Problem

INTRODUCTION: Safe and reliable access to the ventricular system is a necessary skill in the neurosurgical armamentarium. The freehand technique for catheter placement remains an accepted method, yet the inaccuracy rate can be as high as 40%, with as many as 3 passes per procedure, and complication rates between 10-40%. A number of devices have been developed to assist with catheter placement, however, these devices inhibit ergonomics or require larger incisions and expensive navigation technology. METHODS: A novel device for ventricular entry, the DIVE guide, was designed by the first and senior author. 50 patients undergoing extra ventricular drain (EVD) or shunt placement were prospectively enrolled for DIVE assisted catheter placement under an IRB approved study with a non-significant risk (NSR) device designation. The primary outcome is catheter location on CT. Secondary outcomes include number of catheter passes, clinically significant hemorrhages and procedure-related infections. RESULTS: 50 patients were enrolled at a single academic center for ventricular access with DIVE assistance. Indications included subarachnoid or intraventricular hemorrhage, TBI, hydrocephalus, pseudotumor and post-surgical wound drainage. 76% (38/50) underwent right sided placement and 24% (12/20) underwent left. 100% (50/50) had successful cannulation in an average of 1.06 passes. Post procedure head CT confirmed ipsilateral frontal horn or 3rd ventricle placement (Kakarla Grade 1) in 92% (46/50) and 8% (4/50) in the contralateral lateral ventricle (Grade 2). There were no significant tract hemorrhages or procedural infections. CONCLUSIONS: This a prospective study to investigate the safety and efficacy of DIVE-assisted ventricular access. 100% of procedures had successful ventricular cannulation, with 92% achieving Kakarla Grade 1, in an average of 1.06 passes.

Pharmacotherapy of obesity—Competition to bariatric surgery or a meaningful supplement?

Obesity is acomplex chronic disease and requires along-term multimodal approach. The current treatment algorithm for treatment of obesity mainly consists of astepwise approach, which starts with alifestyle intervention followed by or combined with medication treatment, whereas bariatric surgery is often reserved for the last option. This article provides an overview of the currently available conservative medicinal treatment regimens and the currently approved medications as well as medications currently undergoing approval studies with respect to the efficacy and possible side effects. Special attention is paid to the importance of combination treatment of pharmacotherapy and surgery in the sense of amultimodal treatment. The data so far show that using amultimodal approach an improvement in the long-term weight loss and metabolic benefits can be achieved for the patients.

Robot assisted laparoscopic radical prostatectomy with maximal urethral length preservation technique preserves penile length.

Penile shortening is a recognized but neglected side effect of prostate cancer treatment. In this study we explore the effect of maximal urethral length preservation (MULP) technique on penile length preservation after robot assisted laparoscopic prostatectomy (RALP). In an IRB approved study, we prospectively evaluated the stretched flaccid penile length (SFPL) pre and post RALP in subjects with a diagnosis of prostate cancer. The multiparametric MRI (MP-MRI) was utilized for surgical planning if available preoperatively. Repeated measures t-test, linear regression and 2-way ANOVA analyses were performed. A total of 35 subjects underwent RALP. Mean age was 65.8yr (SD: 5.9), preoperative SFPL was 15.57cm (SD: 1.66) and postoperative SFPL was 15.41cm (SD: 1.61) p = 0.68. No change in the postoperative SFPL was recorded among 27 subjects (77.1%) while 5 subjects (14.3%) had 0.5cm shortening, and 3 subjects (8.6%) had 1cm shortening. Pathologic stage, preoperative MP-MRI and body mass index (BMI) were significant predictors of postoperative SFPL on linear regression analysis, p = 0.001. Among 26 subjects with pathologic stage 2 disease, no statistical difference was seen in repeated measures t-test between pre and postoperative SFPL, 15.36 vs 15.3cm, p = 0.08. All subjects were continent by 6months postoperatively, with no complications. We demonstrate that incorporating MULP technique and preoperative MP-MRI preserves SFPL in subjects undergoing a RALP.

Abstract PD2-01: Local and lymphoid immune surveillance mechanisms in “exceptional survivors” of stage 4 cancers following standard of care chemo- and targeted therapies

Abstract Breast cancer patients with advanced metastatic disease can exhibit rapid disease progression, disease stabilisation or partial responses of varying duration. However, for reasons that are not fully elucidated, a small fraction of patients will elicit an exceptional durable response to standard anticancer treatments or survive significantly longer than patients with clinically comparable tumours. Here, we investigate the drivers of immune surveillance mechanisms across breast cancer subtypes in stage IV exceptional survivors (n=13) with matched control cohorts of stage IV typical responders (n=6), early breast cancer patients (n=5) and healthy volunteers (n=17). Peripheral blood mononuclear cells (PBMCs) from patients were stained with 8 panels providing 241 non-redundant immune parameters for flow cytometry analysis. Principle Component Analysis (PCA) showed distinct segregation of the exceptional survivors from the other control groups with an immune signature in exceptional survivors constituting of activated NK, CD8 T cells and gamma delta (gd) T cells pointing towards higher innate immunogenicity in these individuals. Specifically, although these metastatic exceptional responder patients possessed comparable NK cell frequencies, the proportion of NKG2D+CD56dimCD16+ NK cells were significantly enriched compared to the typical responders. Additionally, proportions of CD8+ central memory (CD45RA- CD27+) and effector memory (CD45RA- CD27-) gd T cells, were also seen to be significantly increased. Functional in vitro validation of these findings along with scRNA sequencing of lymph node and tumour tissue is currently underway. To our knowledge, this work is the first to explore in depth the immune signatures in the peripheral blood of exceptional survivors with metastatic breast cancer. Elucidating the immunological reasons for favourable atypical responses alongside functional tumour microenvironment analysis offers unique insights for predictive biomarker identification and discovery of axes that could be exploited therapeutically to benefit those with less favourable responses. Written informed consent was obtained from all individuals in accordance with the Declaration of Helsinki under the following research ethics committee; London-Chelsea approved study (REC ID 13/LO/1248). Citation Format: Helen Kakkassery, Thanussuyah Alaguthurai, Rosalind Graham, Esme Carpenter, Farhana Hossain, Sean Keane, Sheeba Irshad. Local and lymphoid immune surveillance mechanisms in “exceptional survivors” of stage 4 cancers following standard of care chemo- and targeted therapies [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD2-01.

Paper 17: Minimum 5-year Clinical Outcomes of Arthroscopically Repaired Massive Rotator Cuff Tears – Effect of Age on Clinical Outcomes

Objectives: Massive rotator cuff tears (MRCTs) are a frequent and challenging entity encountered by for orthopedic surgeons, accounting for up to 40% of all rotator cuff tears (RCT). Furthermore, the efficacy of repair of MRCTs in older patients is questioned by some. The purpose of this study is to report minimum 5-year outcomes after primary arthroscopic rotator cuff repair (ARCR) of MRCT and the effect that age has on outcomes. We hypothesized that there would be low rates of revision and a high patient satisfaction in a mid-term follow up in those patients treated with a primary ARCR independent of age. Methods: Data was collected prospectively and retrospectively reviewed for this IRB approved study. Inclusion criteria was that patients were a minimum of 5 years out from an ARCR of a MRCT by a single surgeon from February 2006 to November 2016. Patients were excluded if they had glenohumeral osteoarthritis (Hamada >2), fatty infiltration (Goutallier >3), or if they had concomitant pathologies such as labral lesions or chondromalacia that led to additional surgical procedures except for biceps tenodesis/tenotomy and subacromial decompression. MRCTs were defined by the Neer Circle’s Delphi consensus statement as tendon retraction to the glenoid rim and/or a minimum exposed greater tuberosity of at least 67 percent in combination with the Gerber classification of at least two affected tendons. Patient reported outcome (PRO) data was collected preoperatively and evaluated at a minimum follow-up of 5 years postoperatively using the American Shoulder and Elbow Surgeons Score (ASES), Single Assessment Numeric Evaluation Score (SANE), Quick Disabilities of the Arm, Shoulder and Hand Score (QuickDASH), the Short Form 12 physical component summary (SF-12 PCS), and patient satisfaction to assess surgical outcomes at final follow-up. Linear and LOESS regression in addition to correlation was analyzed to assess the effect of age on clinical outcomes. Further, a sub-group analysis of patients over and under 65 was performed. Retears, revision surgery, and surgical complications were recorded. Surgical failure was defined as revision surgery. Results: In total, 188 patients with ≥ 2 tendon RCTs who were at least 5 years out from surgery were identified. After application of exclusion criteria and the Neer Circle’s MRCT definition, 61 patients (mean age: 59.5 years, range: 39.6-73.8; 38 males, 23 females) with a mean follow up of 7.9 years (range 5.0-12.1) included in this study. Final follow-up was obtained in 44 patients (76%). At final follow-up, the mean PROs were significantly improved over preoperative levels for all PROs. The ASES scores improved from 59.4 to 95.0 (p<.001), SANE improved from 66.3 to 89.9 (p>.001), QuickDASH improved from 34.2 to 8.3 (p<.001) and SF-12 PCS improved from 41.5 to 51.3 (p<.001). Median postoperative satisfaction was 10 (range 1-10). Linear and LOESS regression analysis as well as correlation analysis showed that no PRO measures (ASES, SANE, QuickDASH, SF12-PCS, or patient satisfaction) were significantly associated with age at time of surgery. In the subgroup analysis of over and under 65, no significant differences between groups were demonstrated for PROs with the exception of postoperative SF-12 PCS (53.6 vs. 49.1; p=.041). Conclusions: The most important finding in this study is that patients undergoing ARCR of MRCTs experience significant improvements in shoulder function irrespective of patient age.

Abstract P5-07-02: Embryo utilization in young breast cancer patients who have undergone egg harvesting for fertility preservation

Abstract INTRODUCTION: Much progress has been made related to fertility preservation in women diagnosed with breast cancer. This includes heightened awareness of impaired fertility due to breast cancer treatment, increased referrals to fertility specialists and development of safe and expeditious means of egg harvesting. Nevertheless, there has been limited investigation of the ultimate issue in fertility preservation, namely the frequency with which women who have undergone egg harvesting actually pursue childbearing. We have retrospectively reviewed a single institution’s experience with egg and embryo utilization among patients who expressly desired childbearing and underwent egg harvesting after a diagnosis of breast cancer. These issues have also been analyzed relative to race and insurance coverage. METHODS: In an IRB approved study, breast cancer patients treated in our institution between 2010 and 2020 were identified and their post-diagnosis fertility and childbearing history was reviewed. Inclusion criteria were age at presentation ≤ 45 years and diagnosis of either invasive breast cancer or ductal carcinoma in situ. Race (self-reported on clinic intake form) and insurance coverage data were analyzed. In cases of incomplete medical record data, we interviewed patients by telephone. RESULTS: 316 breast cancer patients of reproductive age were identified (average age at diagnosis = 39 years, range: 23 - 45). Of these, 168 patients (53%) were offered fertility referral and 118 (38%) saw a fertility specialist. 91 patients (29%) pursued egg harvesting followed by cryopreservation of eggs in 49 cases and embryos in 41 with 1 case unknown. Over an average of 5 years of follow-up (range: 2 - 12 years), 28 women (31% of those who pursued egg harvesting) utilized the egg or embryo to pursue childbearing. 17 underwent embryo transfer to themselves and 11 used surrogate carriers. To date, this has resulted in 20 childbirths from 24 pregnancies. Four pregnancies are currently ongoing and 1 woman is awaiting embryo transfer. Four patients who had undergone egg harvesting conceived without fertility intervention. Of the 55 Medicaid patients of reproductive age diagnosed with breast cancer, only 8 (15%) met with a fertility specialist, 4 harvested eggs, and none pursued childbearing. HMO/PPO insured patients were significantly more likely than Medicaid patients to pursue egg harvesting and embryo utilization (X2 = 7.320, df = 2, p = 0.026). Of 260 HMO/PPO insured patients, 110 (42%) met with a fertility expert, 87 harvested eggs and 28 pursued embryo transfer. Due to the small sample size of patients who utilized embryos in each racial subgroup, analysis did not yield statistically significant differences across groups (p=0.067). Nevertheless, apparent racial disparities exist. Our data reveal that 5 of 17 (29%) Asian patients and 22 of 62 (36%) White patients utilized embryos as opposed to Black patients (1/4 or 25%), Hispanic patients (0/4 or 0%) and those who identified their race as “other” (1/4 or 25%). CONCLUSIONS: These data demonstrate a low overall rate of cryopreserved egg and embryo utilization among women treated for breast cancer whose earlier pursuit of egg harvesting was evidence of a desire for childbearing. Furthermore, racial and insurance data demonstrate disparities in the pursuit of fertility treatment and utilization of preserved eggs and embryos. Further research will utilize interviews to analyze individual women’s decision-making process relevant to such issues as hormone therapy utilization, concerns about breast cancer recurrence, progression of disease and restraints imposed by relationship status and finances. Given the disparity findings reported here, finances will likely emerge as a significant barrier to childbearing in future qualitative research. Citation Format: Christina Weltz, Daniella Nevid, Alison Pruzan, Elisa Port, Ronald Couri. Embryo utilization in young breast cancer patients who have undergone egg harvesting for fertility preservation [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-07-02.

Diagnostic Utility of 3D Gradient-Echo MR Imaging Sequences through the Filum Compared with Spin-Echo T1 in Children with Concern for Tethered Cord.

Fatty intrathecal lesions are a cause of tethered cord, and detection of these on spinal MR imaging is paramount. Conventional T1 FSE sequences are the mainstay of detecting fatty elements; however, 3D gradient-echo MR images, volumetric interpolated breath-hold examination/liver acquisition with volume acceleration (VIBE/LAVA), are popular, given the increased motion resistance. We sought to evaluate the diagnostic accuracy of VIBE/LAVA compared with T1 FSE for detection of fatty intrathecal lesions. In this retrospective, institutional review board-approved study, 479 consecutive pediatric spine MRIs obtained to evaluate cord tethering between January 2016 and April 2022 were reviewed. Inclusion criteria were patients who were 20 years of age or younger who underwent spine MRIs containing both axial T1 FSE and VIBE/LAVA sequences of the lumbar spine. The presence or absence of fatty intrathecal lesions was recorded for each sequence. If fatty intrathecal lesions were present, anterior-posterior and transverse dimensions were recorded. VIBE/LAVA and T1 FSE sequences were evaluated on 2 separate occasions (VIBE/LAVAs first followed by T1 FSE several weeks later) to minimize bias. Basic descriptive statistics compared fatty intrathecal lesion sizes on T1 FSEs and VIBE/LAVAs. Receiver operating characteristic curves were used to determine minimal fatty intrathecal lesion size detectable by VIBE/LAVA. Sixty-six patients were included, with 22 having fatty intrathecal lesions (mean age, 7.2 years). T1 FSE sequences revealed fatty intrathecal lesions in 21/22 cases (95%); however, fatty intrathecal lesions on VIBE/LAVA were detected in 12/22 patients (55%). Mean anterior-posterior and transverse dimensions of fatty intrathecal lesions measured larger on T1 FSE compared with VIBE/LAVA sequences (5.4 × 5.0 mm versus 1.5 × 1.6 mm, respectively; P values = .039 anterior-posterior; .027 transverse). While T1 3D gradient-echo MR images may have decreased the acquisition time and are more motion-resistant than conventional T1 FSE sequences, they are less sensitive and may miss small fatty intrathecal lesions.

Impact of 3Dprinted models on quantitative surgical outcomes for patients undergoing robotic-assisted radical prostatectomy: a cohort study.

Three-dimensional (3D) printed anatomic models can facilitate presurgical planning by providing surgeons with detailed knowledge of the exact location of pertinent anatomical structures. Although 3D printed anatomic models have been shown to be useful for pre-operative planning, few studies have demonstrated how these models can influence quantitative surgical metrics. To prospectively assess whether patient-specific 3D printedprostate cancer models can improve quantitative surgical metrics in patients undergoing robotic-assisted radical prostatectomy (RARP). Patients with MRI-visible prostate cancer (PI-RADS V2 ≥ 3) scheduled to undergo RARP were prospectively enrolled in our IRB approved study (n = 82). Quantitative surgical metrics included the rate of positive surgical margins (PSMs), operative times, and blood loss. A qualitative Likert scale survey to assess understanding of anatomy and confidence regarding surgical approach was also implemented. The rate of PSMs was lower for the 3D printedmodel group (8.11%) compared to that with imaging only (28.6%), p = 0.128. The 3D printed model group had a 9-min reduction in operating time (213 ± 42min vs. 222 ± 47min) and a 5mL reduction in average blood loss (227 ± 148mL vs. 232 ± 114mL). Surgeon anatomical understanding and confidence improved after reviewing the 3D printed models (3.60 ± 0.74 to 4.20 ± 0.56, p = 0.62 and 3.86 ± 0.53 to 4.20 ± 0.56, p = 0.22). 3D printedprostate cancer models can positively impact quantitativepatient outcomes such as PSMs, operative times, and blood loss in patients undergoing RARP.

Quantitative Ultrasound Biomarkers to Assess Nonalcoholic Fatty Liver Disease.

To assess diagnostic performance of quantitative ultrasound (QUS) biomarkers in assessing hepatic steatosis. We prospectively recruited 125 participants (mean age 54 years) who underwent liver QUS, magnetic resonance imaging (MRI), and laboratory tests within 30 days in this IRB approved study. Based on MRI-proton density fat fraction (MRI-PDFF) and MRE, we divided 125 participants into normal liver, nonalcoholic fatty liver (NAFL) and liver fibrosis (≥F1) groups. We examined diagnostic performance of ultrasound attenuation coefficient (AC), normalized local variance (NLV), superb microvascular imaging-based vascularity index (SMI-VI), and shear wave velocity (SWV) for determining hepatic steatosis and fibrosis using area under receiver operating characteristic curve (AUC). We also analyzed correlations of QUS biomarkers to MRI using Spearman correlation coefficient. We observed significant differences in AC, NLV, and SMI-VI among the three groups (22 participants with normal liver, 78 with NAFL, and 25 with liver fibrosis). AUC of AC, NLV, and SMI-VI for determining ≥ mild steatotic livers (MRI-PDFF ≥5%) was 0.95, 0.90, and 0.92, respectively. AUC of SWV for determining ≥ F1 liver fibrosis was 0.93. The correlation of MRI-PDFF was positive to AC (r=0.91) and negative to NLV (r=-0.74), SMI-VI (r=-0.8) in NAFL group. There was a significant difference in regression slope of AC to MRI-PDFF in livers with and without ≥F1 (0.84 vs 0.91, P=.02). QUS biomarkers have high sensitivity and specificity to determine and grade hepatic steatosis and detect liver fibrosis. The effect of liver fibrosis on the performance of QUS biomarkers in quantifying liver fat content warrants further investigation.

COVID-19 Vaccine Hesitancy and Personality Traits; Results from a Large National Cross-Sectional Survey in Qatar

Attitudes to vaccination arise from a complex interplay of personal and environmental factors. This has been true for the COVID-19 vaccination attitudes too and understanding personal factors would help design immunisation strategies that help in infectious disease control. The five-factor model of personality has been established as a valid construct in exploring individual attitudes and traits. This institutional review board approved study explores the relationship between these five domains of personality and attitudes to COVID-19 vaccination in Qatar which has a migrant majority population. A cross-sectional survey was conducted in Qatar using an online survey link containing validated tools to measure vaccine hesitancy and personality traits. People from diverse ethnic and sociodemographic backgrounds, amounting to 5340 individuals, completed the self-report survey. After controlling for social and demographic variables, individuals scoring significantly higher on Conscientiousness were more likely to refuse the COVID-19 vaccination, while those scoring significantly lower on Openness to experience and Neuroticism were also more likely to refuse COVID-19 vaccination. Both groups of individuals scoring significantly higher and lower on Conscientiousness and Neuroticism, respectively, were more likely to trust their own research than trust endorsement of the COVID-19 vaccine from their doctor or healthcare organisation. The study highlights the highly complex and sometimes contradictory relationship between vaccine hesitancy and personality traits and makes a case for understanding this relationship better in order to inform successful immunisation strategies.

The Australian and New Zealand brain injury lifespan cohort protocol: Leveraging common data elements to characterise longitudinal outcome and recovery

IntroductionCognitive, behavioural, academic, mental health and social impairments are common following paediatric traumatic brain injury (TBI). However, studies are often reliant on small samples of children drawn from narrow age...

A novel syndrome associated with prenatal fentanyl exposure

A novel syndrome was suspected in individuals sharing short stature, microcephaly, distinctive facial features, and congenital anomalies. We enrolled 6 patients in an institutional review board approved study and evaluated medical history, findings, facial photographs, and test results across this original cohort. Four additional cases with similar findings were contributed by clinicians from outside institutions, bringing the number of reported cases to 10 and supporting the existence of this novel syndrome.The 6 individuals enrolled into the institutional review board approved study shared microcephaly, short stature, and distinctive facial features. Congenital malformations included cleft palate, talipes equinovarus or rocker bottom feet, and chordee or hypospadias. Short, broad thumbs, single palmar crease, and mild 2,3 toe syndactyly were present. A hypoplastic corpus callosum was noted in 3 of 5 with appropriate evaluation. Their growth and physical findings were suggestive of Smith-Lemli-Opitz syndrome. Biochemical studies shortly after delivery indicated abnormalities in the cholesterol metabolism pathway that subsequently resolved. No shared genomic or genetic cause was identified. All individuals were born after a pregnancy complicated by prenatal exposure to nonprescription opioids, particularly fentanyl, suggesting fentanyl as a teratogen.Prenatal fentanyl exposure possibly interfered with cholesterol metabolism, giving rise to findings resembling Smith-Lemli-Opitz syndrome. This novel syndrome is clinically recognizable. Four additional cases contributed clinically shared similar findings, increasing the number of cases to 10 and supporting a novel syndrome associated with prenatal fentanyl exposure. Assessment of Shepard and Bradford Hill criteria could be consistent with fentanyl as teratogen, though caution is necessary before assigning causality and data replication is needed.

Machine Learning Model for Chest Radiographs: Using Local Data to Enhance Performance.

To develop and assess the performance of a machine learning model which screens chest radiographs for 14 labels, and to determine whether fine-tuning the model on local data improves its performance. Generalizability at different institutions has been an obstacle to machine learning model implementation. We hypothesized that the performance of a model trained on an open-source dataset will improve at our local institution after being fine-tuned on local data. In this retrospective, institutional review board approved study, an ensemble of neural networks was trained on open-source datasets of chest radiographs for the detection of 14 labels. This model was then fine-tuned using 4510 local radiograph studies, using radiologists' reports as the gold standard to evaluate model performance. Both the open-source and fine-tuned models' accuracy were tested on 802 local radiographs. Receiver-operator characteristic curves were calculated, and statistical analysis was completed using DeLong's method and Wilcoxon signed-rank test. The fine-tuned model identified 12 of 14 pathology labels with area under the curves greater than .75. After fine-tuning with local data, the model performed statistically significantly better overall, and specifically in detecting six pathology labels (P < .01). A machine learning model able to accurately detect 14 labels simultaneously on chest radiographs was developed using open-source data, and its performance was improved after fine-tuning on local site data. This simple method of fine-tuning existing models on local data could improve the generalizability of existing models across different institutions to further improve their local performance.

Histologic Analysis of Buccal Graft Quality Stratified by Tobacco Use in Patients Undergoing Substitution Urethroplasty

To determine if there are histologic differences relative to tobacco exposure in buccal mucosa. Substitution urethroplasty outcomes may be worse in tobacco users and we investigate if the buccal graft is inherently damaged due to chronic tobacco exposure. Subjects undergoing substitution urethroplasty with buccal graft harvest were prospectively consented in this IRB approved study. Subjects with poor dentition were excluded. A detailed tobacco use history was obtained. Cotinine testing was performed day of surgery to confirm or exclude active tobacco use. Trimmed portions of harvested graft were sent for tissue processing. Standard hematoxylin and eosin staining was performed. A single blinded pathologist performed analysis of the slides. Using a scale of none, mild, moderate, or severe slides were analyzed for cytologic atypia, architectural complexity, inflammation, and keratinization. Evidence of vascular damage was noted and the type of inflammation if present was classified. Twenty-five buccal grafts were analyzed. No evidence of vascular damage or cytologic atypia were noted in any grafts. While mild architectural complexity and mild inflammation, typically lymphocytic, were noted in several of the buccal mucosa sections, this did not appear to correlate with tobacco exposure. The majority of grafts demonstrating increased keratinization correlated with significant tobacco exposure, but this was not consistently noted in all those with tobacco use. Buccal mucosa in patients with tobacco exposure did not show significant histologic alterations. Outcomes of substitution urethroplasty may be more impacted by persistent systemic exposure causing local ischemia as opposed to the graft tissue itself.

750: EVALUATION OF IV FENTANYL INFUSION DOSE IN THE INTENSIVE CARE UNIT

Introduction: Fentanyl (F) has a rapid onset of action and short duration of action and is typically given as a continuous infusion for analgesia and sedation in the ICU. There has been concern that F dosing requirements have increased over the past few years. The goal of this study was to retrospectively evaluate the use of F in the ICU to assess whether doses increased over time. Methods: This IRB approved study included intubated ICU adult patients from 2017 - 2021. We identified all patients with F infusions over 24 hours and then randomly pulled 200 patients (40 in each calendar year) to abstract data on F dosing parameters included total length of therapy, time to max dose, and cumulative dose as primary outcomes. F side effects and concomitant diseases were also collected. Continuous variables were analyzed using ANOVA test and discrete variables were analyzed using Kruskal-Wallis test. Results are presented as mean ± SD or percentages. A significant difference in any variable was determined based on p < 0.05. Results: There were no significant differences among background demographics. The average age of the entire sample was 60.1 ± 16.5, and 52% male. Total length of therapy 102.9 ± 75.4, 111.0 ± 106.8, 139.1 ± 173.6, 101.6 ± 88.9, and 102.7 ± 71.6 hours, p>0.05 for each year. Time to max dose (41.2 ± 59.2, 29.6 ± 67.9, 40.2 ± 69.2, 52.9 ± 64.5, and 35.1 ± 37.6 hours), and cumulative dose (11025 ± 11758.7, 10887.5 ± 12450.7, 16587.5 ± 33974.5, 8912.5 ± 8961.4, and 11912.5 ± 10770.3 mcg) for each year was not different, p>0.05. Respiratory, renal, and psychiatric concomitant conditions were significantly different for all years. Regardless of the year, patients who received concomitant F and ketamine had a significant incidence of hypotension, p=0.006. Conclusions: The results of this retrospective review of intubated ICU patients found no difference in F dosing requirements over a five-year period. A significant higher incidence of hypotension was found when patients received F with ketamine. The data may be limited by the varying presence of comorbidities from year to year.

Esophagectomy in octogenarians: is it at a cost?

BackgroundSurgical intervention in the geriatric population has a higher risk of perioperative morbidity and mortality due to frailty, comorbidities, and lack of compensatory physiologic reserve. The literature on esophagectomy in octogenarians is limited and there is concern about elderly patients being with-held surgery. The purpose of this study is to analyze the outcomes of esophagectomies for esophageal cancer in octogenarians to assess the safety of esophagectomy in this population. Methods145 transhiatal esophagectomies performed for esophageal cancer between 2012 and 2020 were retrospectively reviewed in this IRB approved study. Two aborted esophagectomies were excluded. Patient demographics, surgical outcomes, and oncologic outcomes were reviewed. The octogenarian group was analyzed compared to patients younger than 80 years of age. ResultsAmong 143 esophagectomies, 136 patients were <80 years old while 7 were ≥80 years old. Octogenarians received significantly less neoadjuvant therapy compared to younger patients (42.9% vs 80.2%, p = 0.02). No statistically significant difference was noted in complication rate, length of stay (LOS), estimated blood loss (EBL), or mortality. However, octogenarians were found to have an increase in severity of complications compared to younger patients. ConclusionThis study demonstrates that esophagectomy can be performed in carefully selected octogenarians. This comes at a cost with increased severity of complications without an increase in complication rates or mortality. This data suggests that esophagectomy can be offered selectively to older patients with clear expectations and planning for the high risk of more severe post-operative complications.

Patient and Provider Perspectives of Telehealth and In-Person Interventional Radiology Clinic Visits

PurposeTo assess patient and provider satisfaction with interventional radiology (IR) outpatient telehealth and in-person clinic. Materials and MethodsThis institutional review board–approved study analyzed patient satisfaction with clinic via survey after an IR outpatient telehealth or in-person visit. A physician telehealth experience survey was completed by 8 IR physicians. ResultsDuring the initial survey period, 44 (83%) of 53 patients completed a survey via telephone compared with 37 (23%) of 158 patients who were offered an electronic survey during the second survey period. Of 81 respondents, 18 (22%) were in-person and 63 (78%) were via telehealth. Of the respondents, nearly all patients (97%) in the telehealth group reported satisfaction with their telehealth clinic visit, with similar rates of high patient satisfaction between in-person and telehealth visits (P = .51). Most patients (98%) in the telehealth group strongly agreed that their physician’s recommendations were clear in the telehealth visit and that their visit was private, similar to in-person visits (P = .13). A telehealth visit saved time for all patients (100%), with 78% reporting >1 hour of time-saving. All IR physicians (n = 8) reported greater efficiency with telehealth clinic than with in-person clinic and that follow-up patterns would change if telehealth was available. However, all providers (100%) found telephone visits less satisfying than in-person visits, with video visits being either equally satisfying (71%) or less satisfying (29%). ConclusionsPatient satisfaction with the in-person and telehealth outpatient IR clinic was high, with patients and providers reporting time-saving and greater efficiency with telehealth, suggesting that telehealth should remain an important component of outpatient IR clinic care.

Association of Elevated Tricuspid Regurgitation Velocity with Kidney and Cerebrovascular Disease in Children with Sickle Cell Disease

Introduction: Adult patients with sickle cell disease (SCD) develop progressive end-organ injury leading to multi-organ disease and increased mortality. It is plausible that this multi-organ damage begins in pediatric patients. Tricuspid regurgitation velocity (TRV), measured by echocardiography is a surrogate marker for pulmonary hypertension that is a poor prognostic factor in adults with SCD. The utility of screening echocardiograms as a marker of disease severity is being studied in pediatrics. In this study, we assessed associations between elevated TRV with early development of chronic kidney disease (albuminuria), and cerebrovascular disease (CVD). Methods: We performed an IRB approved cross-sectional study to evaluate the prevalence of elevated TRV ≥ 2.5 m/s and its associations with albuminuria and CVD in patients with SCD ages 1-21 years. We included children with a diagnosis of SCD who had at least one echocardiogram performed during an outpatient clinic visit at steady-state for screening for pulmonary hypertension. We categorized patients as receiving either transfusion therapy (chronic transfusion for >12 months), SCD modifying therapy (hydroxyurea, voxelotor, crizanlizumab, or L-glutamine), or no therapy. Patients on both transfusion and a SCD modifying therapy were defined as being on transfusion therapy. We defined albuminuria as patients with two of three consecutive albumin creatinine ratios ≥30mg/g measured during standard clinic visits. Cerebrovascular disease was defined as having either 1) an overt stroke, 2) silent cerebral stroke defined by MRI, 3) vasculopathy by abnormal magnetic resonance angiography (MRA), 4) transient ischemic event defined by stroke symptoms that resolved within 24 hours, or 5) abnormal TCD (>200 cm/second). We performed bivariate analysis utilizing t-test (or Kruskal-Wallis test) and Cochran-Mantel-Haenszel test for continuous and categorical variables respectively. To determine the association between elevated TRV and albuminuria, and elevated TRV and CVD, logistic regression was fit and adjusted for variables that were significant in the bivariate analysis. Using the TRV <2.5m/sec as the reference group, adjusted odds ratios with their accompanying confidence intervals were calculated for those with albuminuria and those with CVD in separate models. All reported P values were 2-sided. Statistical significance was defined as p<0.05. All analyses were performed using Statistical Analysis Software 9.4, (SAS Institute, Cary, NC). Results: Among 166 children with echocardiography, the prevalence of an elevated TRV was 21%. On bivariate analysis, elevated TRV was significantly associated with persistent albuminuria (OR 2.85 (95% CI: 1.27-6.43) and cerebrovascular disease (OR: 2.46 (95% CI: 1.09-5.53) (Table 1). An elevated TRV was also significantly associated with increased age (15.6 vs 12.9 yrs, p=0.005), lower hemoglobin F% (2.5 vs 4.6%, p=0.01), higher absolute reticulocyte count (0.5 vs 0.4 x 106/ µL p=0.005) and chronic transfusion therapy (p=0.04). After adjusting for age, absolute reticulocyte count, HbF and treatment in a multivariable logistic regression, the associations between elevated TRV with either persistent albuminuria (OR: 1.82 (0.71 - 4.67)) and cerebrovascular disease (OR: 1.15 (0.43-3.10)) were no longer statistically significant (Table 1). Our data suggests that with an odds ratio of 2.9 and a prevalence of elevated TRV of 20%, a prospective study of 166 adolescent patients with SCD would be needed to detect the association between elevated TRV and persistent albuminuria with 80% power and 233 children would be needed to detect this difference with 90% power. Conclusion: This data provides additional evidence that around 20% of pediatric patients have an elevated TRV and those patients may also have an increased risk for developing chronic kidney disease and cerebrovascular disease. A larger, prospective cohort study should be conducted to confirm these findings and determine the role of screening echocardiography in pediatric SCD. At minimum, our data suggests that pediatric patients with known chronic kidney disease or cerebrovascular disease should be screened for cardiac complications. Furthermore, longitudinal studies are needed to evaluate the association between elevated TRV in children with early end-organ complications in adults. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Pediatric Sickle Cell Disease: A Potential Role for the Complement System

Background: Sickle cell disease (SCD) is one of the most common life-threatening hereditary red blood cell (RBC) disorders, with an estimated 300,000 infants born annually with the disease. In SCD, a mutation in the gene for β-globin results in rigid sickled RBCs that have difficulty navigating the vasculature and increased risk for forming blockages in the micro-vessels within organs, leading to RBC lysis, endothelial cell (EC) damage, ischemia/reperfusion injury, and extremely painful vaso-occlusive crises (VOC). Overtime, this can lead to stroke, serious organ damage, and other complications, resulting in a reduced life expectancy. Emerging research points to the involvement in SCD of complement, an important part of the innate immune system composed of proteins that are activated to help clear invaders and damaged cells from the body. Recent work by others has demonstrated that complement activation occurs in patients with SCD in both acute and chronic phases of the disease, and may be associated with disease severity and VOC (Fig 1A). This study aims to assess the role of complement activity in children with SCD during acute crisis and disease steady state. Methods: Pediatric patients aged 0-18 with SCD (HbSS or HbS/β0) managed at The Hospital for Sick Children (Toronto, Canada) were enrolled in this REB approved study during hospital admission with diagnosed VOC or acute chest crisis (ACS) not caused by infection. Patient serum and plasma was collected during hospital admission (crisis) and during follow-up (steady state, 3 to 12 months following an acute crisis) simultaneously with routine bloodwork. Patients with >3 crisis admissions in the previous 12 months or requiring admission for >7 days were excluded. Pooled normal human serum (NHS) was collected from healthy volunteers for use as a control. Complement activity was measured using the WIESLAB Complement System Screen (Svar Life Science). Immunofluorescence (IF) imaging was used to measure the deposition of C3b and C5b-9 complement proteins on the surface of ECs exposed to patient serum or NHS. Data were analyzed using an unpaired t-test or one-way ANOVA with Tukey's multiple comparisons. Results: Thus far, 58 patients have been enrolled in the study. SCD crisis patients showed significantly decreased hemoglobin compared to steady state (Table 1). Complement activity was assessed for 6 crisis and 5 steady state patients. There was equal classical and alternative pathway activity during disease steady state and crisis, which indicates no in vivo complement protein depletion in patients, with an interesting trend showing elevated MBL pathway activity during crisis compared to steady state (Figure 1B). Complement deposition was assessed via IF in 19 crisis, 16 steady state patients, and 6 replicates of NHS. IF assay data show significantly elevated deposition of C3b on ECs when comparing patient crisis samples and healthy controls, with trends suggesting a potential difference in C5b-9 deposition between NHS and crisis patients, as well as differences in complement deposition between steady state and crisis patients (Fig 1C). Conclusion: Our preliminary data shows complement is active in SCD, resulting in elevated C3b deposition on ECs during SCD crisis. Although not statistically significant, trends suggesting a difference in C5b-9 deposition and differences between steady state and crisis patients are encouraging, as a small change in intravascular complement activity may still have significant physiological consequences. Future work is focused on further quantifying complement activity and understanding its mechanism, assessing the in vitro functional consequences of this on the surface of ECs, and investigating complement blockade as a potential treatment. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal