Multiple Centers Research Articles

How to Avoid and Handle Problems in the Placement of Cement-Augmented Fenestrated Percutaneous Pedicle Screws?

BACKGROUND AND OBJECTIVES: Pedicle screws with a central cannula and fenestrations allow cement augmentation, providing lower risk for screw loosening and pullout, especially in these patients with poor bone quality. This study aims to offer suggestions for resolving issues and reducing complications associated with the use of cement-augmented fenestrated pedicle screws. METHODS: A retrospective study was conducted across multiple centers on patients who received fenestrated pedicle screws with cement augmentation (CAFPS). Using 2-dimensional fluoroscopy guidance, we placed over 800 screws in 137 patients. Based on our analysis of common challenges and complications, 10 tips were compiled, that we believe are crucial for successfully implementing this technique, regardless of the brand or instrument used. RESULTS: The 10 tips included the following: (1) Indications of cement-augmented fenestrated pedicle screws; (2) use the K-wire blunt end in osteoporotic vertebrae; (3) know the longitude and diameter of the screw, by the measurement of the vertebrae to treat; (4) do not go bicortical; (5) clean the way of the screws fenestrae with saline; (6) protecting screw extensors with gauze; (7) measuring time and volume; (8) gently and smoothly introduce the cement; (9) do not panic. The presence of cement in the posterosuperior area adjacent to the pedicle does not necessarily indicate a leakage into the canal; and (10) fenestrated screw removal. CONCLUSION: The implementation of these tips could enhance technique performance and minimize complications in cement-augmented fenestrated pedicle screw placement.

From code sharing to sharing of implementations: Advancing reproducible AI development for medical imaging through federated testing

BackgroundThe reproducibility crisis in AI research remains a significant concern. While code sharing has been acknowledged as a step toward addressing this issue, our focus extends beyond this paradigm. In this work, we explore “federated testing” as an avenue for advancing reproducible AI research and development especially in medical imaging. Unlike federated learning, where a model is developed and refined on data from different centers, federated testing involves models developed by one team being deployed and evaluated by others, addressing reproducibility across various implementations. MethodsOur study follows an exploratory design aimed at systematically evaluating the sources of discrepancies in shared model execution for medical imaging and outputs on the same input data, independent of generalizability analysis. We distributed the same model code to multiple independent centers, monitoring execution in different runtime environments while considering various real-world scenarios for pre- and post-processing steps. We analyzed deployment infrastructure by comparing the impact of different computational resources (GPU vs. CPU) on model performance. To assess federated testing in AI models for medical imaging, we performed a comparative evaluation across different centers, each with distinct pre- and post-processing steps and deployment environments, specifically targeting AI-driven positron emission tomography (PET) imaging segmentation. More specifically, we studied federated testing for an AI-based model for surrogate total metabolic tumor volume (sTMTV) segmentation in PET imaging: the AI algorithm, trained on maximum intensity projection (MIP) data, segments lymphoma regions and estimates sTMTV. ResultsOur study reveals that relying solely on open-source code sharing does not guarantee reproducible results due to variations in code execution, runtime environments, and incomplete input specifications. Deploying the segmentation model on local and virtual GPUs compared to using Docker containers showed no effect on reproducibility. However, significant sources of variability were found in data preparation and pre-/post- processing techniques for PET imaging. These findings underscore the limitations of code sharing alone in achieving consistent and accurate results in federated testing. ConclusionAchieving consistently precise results in federated testing requires more than just sharing models through open-source code. Comprehensive pipeline sharing, including pre- and post-processing steps, is essential. Cloud-based platforms that automate these processes can streamline AI model testing across diverse locations. Standardizing protocols and sharing complete pipelines can significantly enhance the robustness and reproducibility of AI models.

Advances in artificial intelligence for predicting complication risks post-laparoscopic radical gastrectomy for gastric cancer: A significant leap forward

In a recent paper, Hong et al developed an artificial intelligence (AI)-driven predictive scoring system for potential complications following laparoscopic radical gastrectomy for gastric cancer patients. They demonstrated that integrating AI with random forest models significantly improved the preoperative prediction and patient outcome management accuracy. By incorporating data from multiple centers, their model ensures standardization, reliability, and broad applicability, distinguishing it from the prior models. The present study highlights AI's potential in clinical decision support, aiding in the preoperative and postoperative management of gastric cancer patients. Our findings may pave the way for future prospective studies to further enhance AI-supported diagnoses in clinical practice.

Two-Dimensional π-d Conjugated Conductive Metal-Organic Framework with Triple Active Centers as High-Performance Cathodes for Flexible Zinc Batteries.

Conductive metal-organic frameworks (C-MOFs) have received extensive interest in high-performance zinc-ion batteries (ZIBs) owing to multi-redox sites and high electrical conductivity. Here, we present a π-d C-MOF by coordinating 2,3,5,6-tetraaminobenzoquinone (TABQ) ligands with Cu2+ ions (2D Cu-TABQ) acting as cathodes for ZIBs. Benefiting from a triple active center (Cu2+, C=O, and C=N), 2D Cu-TABQ shows an ultra-high reversible capacity of 297.7 mAh g-1at 0.2 A g-1. Meanwhile, 2D Cu-TABQ also has superior cycle stability with a capacity of up to 98.2 mAh g-1 after 1000 times at 2.0 A g-1. Considering the instability of the ligand bonds of C-MOFs in aqueous electrolytes,this work uses gel electrolytes to reduce the dissolution of organic ligands into the electrolyte, thus suppressing the shuttle effect, significantly improving the cycling stability of 2D Cu-TABQ. The flexible battery assembled by 2D Cu-TABQ shows excellent capacity retention (64.4%) after 50 times at 0.2 A g-1, which is significantly better than 36.4% in the common electrolyte, as well as outstanding bending resistance and electrochemical properties at different folding angles. This investigation will highlight the electrochemical application of C-MOFs in flexible zinc ion batteries and offer novel ideas for the structural design of cathodes with multiple active centers.

Isolation and Identification of Bacterial Pathogens from Blood Cultures in a Tertiary Care Hospital and Their Clinical Correlation

Objective: This study aimed to isolate and identify bacterial pathogens from blood cultures of patients with suspected bloodstream infections (BSIs) in a tertiary care hospital, analyze their antimicrobial susceptibility patterns, and establish clinical correlations. Methods: A cross-sectional study was conducted in the Microbiology Department of a tertiary care hospital. Blood samples from 60 patients were collected aseptically, processed using BACTEC, and cultured on blood and MacConkey agar. Bacterial isolates were identified based on colonial morphology, Gram staining, and biochemical tests. Antibiotic susceptibility testing was performed using the modified Kirby-Bauer disk diffusion method according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Results: The overall culture positivity rate was 26%, with higher positivity among female patients (31.57%) and neonates or infants under six months (26%). Klebsiella pneumoniae was the most frequently isolated pathogen (53.33%), followed by Staphylococcus aureus (20.00%), Escherichia coli (13.33%), and Citrobacter species (13.33%). Klebsiella pneumoniae showed high resistance to ceftazidime and piperacillin, while remaining sensitive to cefoperazone and tobramycin. Staphylococcus aureus isolates were resistant to penicillin and erythromycin but sensitive to vancomycin and cefazolin. The prevalence of multidrug resistance among isolates underscores the need for targeted empirical therapy. Conclusion: Klebsiella pneumoniae emerged as the primary pathogen in BSIs, with significant resistance to commonly prescribed antibiotics. These findings highlight the necessity for enhanced infection control measures, especially in NICUs, and the implementation of local antibiograms to guide effective antibiotic therapy and mitigate resistance trends. Further research across multiple centers is recommended to validate these findings and inform broader clinical guidelines.

Large-scale deep proteomic analysis in Alzheimer's disease brain regions across race and ethnicity.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, yet our comprehension predominantly relies on studies within non-Hispanic White (NHW) populations. Here we provide an extensive survey of the proteomic landscape of AD across diverse racial/ethnic groups. Two cortical regions, from multiple centers, were harmonized by uniform neuropathological diagnosis. Among 998 unique donors, 273 donors self-identified as African American, 229 as Latino American, and 434 as NHW. While amyloid precursor protein and the microtubule-associated protein tau demonstrated higher abundance in AD brains, no significant race-related differences were observed. Further proteome-wide and focused analyses (specific amyloid beta [Aβ] species and the tau domains) supported the absence of racial differences in these AD pathologies within the brain proteome. Our findings indicate that the racial differences in AD risk and clinical presentation are not underpinned by dramatically divergent patterns in the brain proteome, suggesting that other determinants account for these clinical disparities. We present a large-scale proteome (∼10,000 proteins) of DLPFC (998) and STG (244) across AD cases. About 50% of samples were from racially and ethnically diverse brain donors. Key AD proteins (amyloid and tau) correlated with CERAD and Braak stages. No significant race-related differences in amyloid and tau protein levels were observed in AD brains. AD-associated protein changes showed a strong correlation between the brain proteomes of African American and White individuals. This dataset advances understanding of ethnoracial-specific AD pathways and potential therapies.

Enhancing safety: Multi-institutional FMEA and FTA on -based radio-pharmaceutical therapy.

This study investigates potential failure modes and conducts failure mode and effects analysis (FMEA) and fault tree analysis (FTA) on the administration of DOTATATE (LUTATHERA) and PSMA-617 (PLUVICTO). The quality management (QM) process in radiopharmaceutical therapies (RPTs) requires collaboration between nuclear medicine (NM) and radiation oncology (RO) departments. As part of a multi-institutional study, we surveyed various departments to identify and analyze failure modes, leading to a proposed comprehensive QM program. RPT teams in RO or NM clinics can benefit from this study by continually improving theirpractice. We reviewed the literature to investigate the administration of Pluvicto and Lutathera, focusing on prospective procedural failures and potential failure modes (PFMs) and their outcomes. We distributed an FMEA survey to multiple experienced centers in -based RPTs and calculated risk priority number (RPN) for various PFM. We conducted an FTA using this information to pinpoint the root causes of potentialfailures. The findings from the literature review and survey responses on the prospective study have identified several critical areas at risk of failure. These areas include non-optimized treatment delivery, inadequate patient monitoring, and lack of safety training, leading to radiation contamination from the dose excreted by the patients after treatment administration. A segmented FTA was created based on the FMEA results, focusing on radiation contamination with a high RPN value. By identifying the root causes of failures and proposing targeted improvements to the existing QM measures, this analysis enhances safety in treatment delivery of -based RPTs. Given the limited number of prospective risk analysis studies in RPTs, our research addresses the necessity for more such studies and recommends methods to apply this study to otherRPTs.

Vibrational Mode-Dependent Circular Dichroism of Jet-Cooled Styrene Oxide.

Vibrational mode-dependent circular dichroism (CD) effects in vibrational CD spectra are often used to determine the handedness of molecules with multiple chiral centers. Here, we investigate vibrational mode-dependent CD effects in the electronic CD spectra of jet-cooled (R)-(+)- and (S)-(-)-styrene oxide obtained by using resonant two-photon ionization CD (R2PICD) spectroscopy. Although most fundamental vibronic bands demonstrated CD signatures consistent with that of the origin band, the overtone and combination bands exhibited opposite CD signatures. Theoretical calculations suggest that CD in fundamental bands are primarily governed by Franck-Condon contributions, whereas Herzberg-Teller contributions, which reflect the influences of vibrational modes on CD values, become more significant in overtone and combination bands. These results underscore the potential of mode-dependent vibronic CD signals in R2PICD spectra for determining the absolute configurations of molecules with multiple chiral centers.

Abstract 4146311: Cardiac Thickening, Cell Free DNA, and Rejection in the 2 nd Porcine Cardiac Xenograft

Introduction/Background: A 58-year-old man with inotrope dependent heart failure was declined for allotransplant and MCS at multiple centers and was transplanted with a 10 gene-edited porcine cardiac xenograft under FDA expanded access Investigational New Drug (eIND) approval. After requiring perioperative transfusions, by post operative day (POD) 13, endomyocardial biopsy revealed antibody and complement deposition without damage or cellular infiltrate. Hemodynamic decompensation on POD 29 prompted biopsy revealing antibody mediated rejection (AMR). The patient required ECMO support POD31 and chose comfort care POD 40. Research Questions/Hypothesis: The cardiac xenograft doubled in mass from implant to autopsy. Donor derived cell free DNA (cfDNA) correlated temporally with the rejection findings. These processes are hypothesized to correlate. Approach: Routine TTE measurements of diastolic LV posterior wall dimension (LVPWd), intraventricular septal dimension (IVSd), LV mass, and LV mass index were taken. Donor derived cfDNA was measured weekly and PRN (Care Dx Inc., Brisbane, CA). Pearson correlation coefficient analysis was conducted in GraphPad Prism 10 (Dotmatics, Boston, MA). Results/Data: POD 26 TTE measurements indicated thickening graft. POD 30 cfDNA began elevating. cfDNA correlated moderately with LVPWd (r = 0.43, p=0.4) and IVSd (r= 0.5, p=0.31) less so with LV mass (r= 0.28, p=0.59) and LV mass index (r=0.34, p=0.51) Conclusions: Xenograft cardiac thickening measured on TTE preceded elevation in cfDNA. Both were moderately correlated and temporally corresponded to biopsy diagnosed AMR and ultimate graft failure. Future xenograft surveillance will likely benefit from multimodal approach.

Abstract 4127345: National Cohort Study on Hypertensive Disorders of Pregnancy Among Women with Congenital Heart Disease: Insights from Multiple Centers

Background: Hypertensive disorders of pregnancy (HDP) are among the primary reasons for maternal and perinatal deaths globally. Encompassing chronic hypertension, pregnancy induced hypertension (PIH), and preeclampsia, HDP are among the most frequent complications encountered during pregnancy. Considering the emerging congenital heart disease (CHD) population globally, research on HDP in pregnancies with CHD is urgently needed. Methods: Outcomes for 2220 pregnant women with CHD were evaluated retrospectively from 1993 to 2016 and prospectively from 2017 to 2019 from 7 tertiary hospitals. Maternal death, cardiac complications, obstetric and offspring complications of completed pregnancies and their demographics, cardiac characteristics, and comorbidities were collected. To identify the risk factors for HDP, univariate and multivariate analysis were performed through logistic regression. Results: Of 2220 completed pregnancies with CHD from 7 tertiary institutions, 77 women had PIH, and 76 women had preeclampsia. The main CHD diagnosis of patients with PIH was shunt lesion (including ASD, VSD, and PDA), left heart abnormality (including AS/AI, BAV, and COA), and single ventricle (SV). The main CHD diagnosis of patients with preeclampsia was shunt lesion (including ASD, VSD, and PDA), left heart abnormality (including AS/AI and MS/MI), and right heart abnormality (including TOF, PS/PAS/PI, DORV and DCRV). In parturients with PIH, the mortality and incidence of heart failure were 2.60% and 15.58%, respectively. In parturients with preeclampsia, the mortality and incidence of heart failure were 6.58% and 23.68%, respectively. Pregnancies with HDP had a significantly higher incidence of adverse maternal and offspring events than pregnancies without HDP. Independent risk factors for HDP included multiple gestation, use of medically assisted reproduction, having elevated brain natriuretic peptide (BNP) level, delayed first ANC visit, and absence of strict antenatal supervision. Conclusion: In summary, the presence of HDP in women with CHD significantly increased the risk of mortality and morbidity for both the mother and the child, particularly in cases involving preeclampsia.

Can computer vision / artificial intelligence locate key reference points and make clinically relevant measurements on axillary radiographs?

Computer vision and artificial intelligence (AI) offer the opportunity to rapidly and accurately interpret standardized x-rays. We trained and validated a machine learning tool that identified key reference points and determined glenoid retroversion and glenohumeral relationships on axillary radiographs. Standardized pre and post arthroplasty axillary radiographs were manually annotated locating six reference points and used to train a computer vision model that could identify these reference points without human guidance. The model then used these reference points to determine humeroglenoid alignment in the anterior to posterior direction and glenoid version. The model's accuracy was tested on a separate test set of axillary images not used in training, comparing its reference point locations, alignment and version to the corresponding values assessed by two surgeons. On the test set of pre- and post-operative images not used in the training process, the model was able to rapidly identify all six reference point locations to within a mean of 2mm of the surgeon-assessed points. The mean variation in alignment and version measurements between the surgeon assessors and the model was similar to the variation between the two surgeon assessors. This article reports on the development and validation of a computer vision/artificial intelligence model that can independently identify key landmarks and determine the glenohumeral relationship and glenoid version on axillary radiographs. This observer-independent approach has the potential to enable efficient human observer independent assessment of shoulder radiographs, lessening the burden of manual x-ray interpretation and enabling scaling of these measurements across large numbers of patients from multiple centers so that pre and postoperative anatomy can be correlated with patient reported clinical outcomes. Level III Study of Diagnostic Test.

Abstract 4141442: The Feasibility and Adherence of Online Intensive Cardiac Rehabilitation Program for Coronary Artery Disease-A pilot Study

Introduction/Background: Remote cardiac rehabilitation is becoming more popular, but most are exercise-based cardiac rehabilitation programs, and online intensive cardiac rehabilitation (ICR) programs that include not only exercise training but also dietary guidance, stress management, and group support have not been widespread. Research Questions/Hypothesis: Whether high adherence and improvement of CAD risk factors demonstrated for the online ICR program. Goals/Aims: We assessed the program adherence by participation rate as the primary endpoint and physical findings, typical CAD risks and nutritional indices as the secondary endpoint. Methods/Approach: The J-ICR program provides online instruction using Zoom (San Jose, CA: Zoom Video Communications Inc.). The program consisted of four parts: aerobic exercise training, dietary education for the Japan diet, stress management training through mindfulness, and group support (10 participants per group) for 3 hours per session, once a week for 12 weeks (36 hours total). Twenty-two patients were enrolled and adherence to the program was examined. Changes in CAD risk factors were also analyzed. Results/Data: After excluding 3 patients who withdrew consent before the program, the current study population consisted of 19 male participants. The mean age was 66 years old, 95% had hypertension, 37% had diabetes mellites and all had hyperlipidemia. Eight patients had myocardial infarction and 15 cases of angina pectoris. The average participation rate of the program was 90.2% and there was no drop out during the program. As the secondary endpoint, body weight （69.2kg vs. 68.2kg; p=0.02), systolic and diastolic blood pressure (126.8mmHg vs. 121.4mmHg; p<0.01 and 79.5mmHg vs. 77.6mmHg; p=0.18), LDL cholesterol (78.9mg/dl vs 77.6mg/dl; p=0.68), HbA1c (6.3% vs. 6.4%; p=0.39), and amount of sodium intake (9.5 g/day vs. 9.5g/day; p=0.68) and total energy intake (2,137kcal/day vs. 2,076kcal/day; p=0.25). Conclusion: The J-ICR program is feasible and may yield improvements in CAD risk factors such as body weight and systolic blood pressure. Since this is a pilot study to explore the feasibility of the online J-ICR, its secondary prevention effect should be verified with appropriately powered randomized trials at multiple centers.

Abstract 4138310: Successful Endovascular Closure of Ascending Aortic Pseudoaneurysm Using Atrial Septal Defect Occluder

Introduction: Ascending aortic pseudoaneurysms are mostly related to either surgery or non-surgical trauma. Any pseudoaneurysm arising from graft anastomoses, regardless of size or location, must be repaired due to the potential for catastrophic rupture. Traditional surgical intervention has a high mortality rate, but percutaneous treatment has emerged as an alternative. We present such a case of pseudoaneurysm treated by percutaneous intervention using a 6-mm Amplatzer device. Case: A 77-year-old female with a history of type A aortic dissection s/p emergent repair with a 32 mm tube graft one year ago presented with chest pain radiating to her back. Initial vital signs showed a BP of 185/105, SaO2 98% on RA, 98.3 F, HR 98 bpm, and RR 24/min. A chest CT scan suggested a pseudoaneurysm at the proximal anastomotic site of the aortic graft (Figs. 1A and B). Serial troponin and EKGs were unremarkable for acute ischemia. Multiple quaternary centers declined intervention due to the high risk of redo sternotomy for open repair and patient frailty. After multidisciplinary discussions, it was felt that percutaneous closure with an Amplatzer device was possible without coronary obstruction. In the catheterization lab, a TEE probe was placed to visualize the pseudoaneurysm of the ascending aorta (Fig. 1C). Angiography showed the aneurysm coming off the posterior aorta just above the noncoronary cusp, with the neck measuring ~6 mm (Fig. 1D). The aneurysm was successfully engaged using an 8-French sheath and an 8-French AL1. Based on measurements from the TEE and the angiogram, a 6 mm ASO device was used. After device deployment and release, aortograms showed that the pseudoaneurysm was excluded (Fig. 1H). Assessment with TEE and CTA showed no residual flow in the pseudoaneurysm (Fig. 1 E–G). Conclusion: Using an atrial septal occluder, endovascular intervention may be a safe and effective alternative to surgery for treating the ascending aortic pseudoaneurysm, especially in patients with a high prohibitive surgical risk. Longitudinal follow-ups are needed to comment on long-term mortality benefits for these individuals.

Real-world outcomes of everolimus-based treatment in a Taiwanese cohort with metastatic HR+/HER2- breast cancer.

Everolimus was the first orally targeted therapy for certain cancers. It was introduced before CDK4/6 inhibitors and is widely used to treat advanced hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. This study presents comprehensive findings including updated data and long-term survival analyses focusing on patients with HR+/HER2- metastatic breast cancer who received everolimus-based treatment. The objectives were to assess the impact of everolimus on overall survival (OS) and progression-free survival (PFS) by treatment line, and to evaluate its role in therapeutic strategies in a real-world setting. We included 299 women aged over 20 years with histologically confirmed HR+/HER2- breast cancer who received everolimus-based treatment from multiple medical centers in Taiwan. Survival curves were generated using the Kaplan-Meier method, with the log-rank test for comparisons. Univariate and multivariate analyses were performed using a Cox proportional hazards regression model. Adverse effects were graded according to the Common Terminology Criteria for Adverse Events version 5.0. The median PFS was 5.6 months, and the median OS was 60.1 months. Patients receiving everolimus treatment in three or more lines and those who underwent chemotherapy prior to everolimus-based treatment had a significantly shorter PFS but longer OS. Patients with liver and central nervous system metastases had significantly shorter PFS and OS. The disease control rate was 51.5%, and the overall response rate was 8.0%. These findings support current guidelines and advocate for the inclusion of everolimus in treatment plans for patients with metastatic HR+/HER2- breast cancer, particularly in late-line treatment, with careful consideration of the benefit-risk profile for each patient.

Abstract 4117032: Investigating the natural history and risk factors underlying deterioration in early-stage hypertrophic cardiomyopathy: findings from SOLENOID

Background: Understanding the natural history and factors contributing to heterogeneous outcomes in patients with early-stage hypertrophic cardiomyopathy (HCM) is crucial to improving patient management. Aim: Utilizing a real-world data cohort spanning multiple centers, we described the natural history of early-stage HCM patients and identified risk factors for disease progression. Methods: SOLENOID is an observational study conducted in five academic centers (two in France, UK, Spain and the US). Inclusion criteria were patients with confirmed HCM seen between 2010 and 2022 in NYHA class I, or in “early stage” NYHA class II (defined by an NT-pro BNP<300 pg/ml, resting or provoked LVOT<50 mmHg, LAVi<35 ml/m2, E/e’<14, without a history of atrial fibrillation (AF), and not on HCM-specific therapy). The endpoint was a composite of NYHA class worsening, new onset of AF and cardiovascular hospitalization. To identify risk factors, univariate analyses were conducted in each center, and then aggregated through a meta-analysis. Results: A total of 1044 patients were included with a median follow-up of 3.9 years (IQR 1.5-7.0). The mean age was 53±16 years, with 30% females and 42% of NYHA I were treated with beta-blockers. Genetic tests in 57% of patients revealed mutations, primarily in MYBPC3 (29%) and MYH7 (12%). During follow-up, the composite endpoint has an incidence of 27% and 41% at 3 and 5 years. The main contributor was NYHA class worsening with an incidence of 24% and 35% at 3 and 5 years. AF at inclusion (log-HR=1.56, p<0.001), baseline level of NT-proBNP (log-HR=0.75, p<0.001) and age at inclusion (log-HR=0.24, p=0.005) were the main predictors of the composite endpoint. Conclusion: Nearly 30% of the early-stage HCM patients experienced disease progression within a 3 year follow-up period, highlighting a medical unmet need. Further studies are needed to assess whether the population characterized by elevated NT-proBNP, or pre-existing AF at inclusion, may benefit from more intensive surveillance and, in future HCM-specific therapy.

Expanding the Genetic and Phenotypic Spectrum of Mowat-Wilson Syndrome: A Study of 10 Turkish Patients With an Intrafamilial Recurrence Caused by First Intragenic Large Deletion.

Mowat-Wilson syndrome (MWS) is a complex disorder caused by heterozygous ZEB2 gene variations creating haploinsufficiency. The main clinical features are evolving facial dysmorphism, intellectual disability, eye and brain malformations, and various organ anomalies. Our study examines 10 Turkish patients, who had clinical diagnosis, underwent evaluation, clinical investigations, and genetic tests in multiple tertiary centers across Türkiye, and were molecularly diagnosed with MWS. Molecular analysis with sequencing techniques alongside array testing unveiled disease-causing variations in addition to novel variants, including two siblings with recurrent multiexon deletion. Clinical presentations varied, featuring neurodevelopmental delay and characteristic facial traits and organ malformations across all cases, alongside less frequently reported manifestations such as laryngomalacia or rocker bottom feet in addition to new features such as macroorchidism and osteoporosis. Our findings expand the genetic and phenotypical spectrum of MWS, and hint at potential implications of gonadal mosaicism. While establishing clear genotype-phenotype correlations poses challenges, comprehensive genetic testing remains pivotal for precise diagnosis and management. The study highlights the complexity of MWS genetics, with potential implications of gonadal mosaicism on recurrence. Further research is needed to elucidate mechanisms driving phenotypic variability, potential hotspots, and mechanisms for recurrent variations. We report on the largest cohort with MWS from Türkiye.

INNV-38. 3 DAYS-ON-1 DAY-OFF FRACTIONATED USE PROTOCOL FOR IMPROVED COMPLIANCE AND PREVENTATIVE SKIN SAFETY FOR USE OF TUMOR TREATING FIELDS: PRACTICE IMPROVEMENT STRATEGY IN NEURO-ONCOLOGY

Abstract BACKGROUND Compassionate care delivery requires that providers understand patient values and adopt practices aimed to improve the quality of extended survival. Many brain tumor clinical trials measure survival outcomes based on therapeutic interventions, but often fail to anticipate patient noncompliance and the provider’s ability to communicate the plan. Tumor Treating Fields (TTFields) is an FDA-approved locoregional, noninvasive therapy worn on the scalp to treat glioblastoma (GBM). When worn, TTFields therapy disrupts cancer cell viability and delays tumor progression but is complicated by mild-moderate skin irritation and real-world inconvenience of the unclear recommendation to wear the device an average of “≥18 hours/day or 75% of the time”. We simplified the physician instructions to encourage patient compliance and skin safety on TTFields. METHODS Adults with GBM were provided an easy-to-follow flow chart and advised across multiple centers to follow the 3-days-on (72 hours) and 1-day-off (16–24 hours) TTFields therapy use schedule and given skin-specific wound prevention guidance (cleansing selenium-based shampoo and reparative skin-barrier moisturizing) during the ‘off day’. We evaluated the ease to explain the 3-on-1-off schedule, patient adherence, and the presence and severity of skin AEs during follow-up visits. REAL-WORLD PRACTICE OUTCOMES Seventy-six patients received TTFields therapy using the 3-on-1-off protocol between 2015 and 2021 at two US healthcare centers. The median age was 57 years (range 25–81). The mean time on TTFields therapy was 73 weeks. Skin AEs occurred in 5% of patients on the 3-on-1-off protocol, as compared to 16% and 52% reported on EF-11 (NCT00379470) and EF-14 (NCT00916409) GBM studies, respectively. Majority of AEs were mild, and no patients discontinued TTFields therapy or modified electrode placement due to skin AEs while on the 3-on-1-off protocol. CONCLUSION We report real-world data confirming a practice improvement for patient compliance using a novel 3-on-1-off protocol which minimizes skin AEs and treatment interruptions to improves patient outcomes. An ounce of prevention is worth a pound of cure.

Development and validation of a risk prediction model for postpartum urinary incontinence in primiparas with singleton pregnancies: a multicenter clinical investigation

BackgroundPostpartum urinary incontinence (UI) is a serious condition that significantly affects the quality of life. Several studies have demonstrated that it is associated with pelvic floor dysfunction. This study aimed to develop and validate a UI risk prediction model to identify primiparas with singleton pregnancies at high risk.MethodsA multistage stratified random sampling process was used. UI was measured using the International Standard Consultation on Incontinence Questionnaire Form (a modified Bristol questionnaire, ICIQ-FLUTS). Records of 1,340 primiparas with singleton pregnancies were reviewed, and data were collected from January 2014 to December 2014 in multiple centers. A univariate logistic regression analysis was performed, followed by a multivariable logistic regression analysis of the data. Using bootstrap resampling, we constructed a nomogram to assess postpartum UI risk.ResultsA total of 1,340 patients were enrolled, including 345 with postpartum UI and 995 with non-postpartum UI. The occurrence of postpartum UI was significantly related to the mode of delivery, family history of UI, coffee or tea consumption, antenatal UI, and frequent cough. The nomogram exhibited good discriminatory ability with a C-index of 0.718 (95% confidence interval: 0.684–0.752) and a bootstrap-corrected C-index of 0.716. Additionally, the calibration curve demonstrated that the predicted outcomes aligned well with the actual observations. Ultimately, the decision curve analysis indicated that the nomogram exhibited favorable clinical applicability.ConclusionThe decision curve analysis suggests that the nomogram could provide clinical value. The clinician will then feel more confident about making clinical recommendations regarding postpartum UI screening for primiparous women with singleton pregnancies.

Integrated Deep Learning Model for the Detection, Segmentation, and Morphologic Analysis of Intracranial Aneurysms Using CT Angiography.

"Just Accepted" papers have undergone full peer review and have been accepted for publication in Radiology: Artificial Intelligence. This article will undergo copyediting, layout, and proof review before it is published in its final version. Please note that during production of the final copyedited article, errors may be discovered which could affect the content. Purpose To develop a deep learning model for the morphologic measurement of unruptured intracranial aneurysms (UIAs) based on CT angiography (CTA) data and validate its performance using a multicenter dataset. Materials and Methods In this retrospective study, patients with CTA examinations, including those with and without UIAs, in a tertiary referral hospital from February 2018 to February 2021 were included as the training dataset. Patients with UIAs who underwent CTA at multiple centers between April 2021 to December 2022 were included as the multicenter external testing set. An integrated deep-learning (IDL) model was developed for UIA detection, segmentation and morphologic measurement using an nnU-net algorithm. Model performance was evaluated using the Dice similarity coefficient (DSC) and intraclass correlation coefficient (ICC), with measurements by senior radiologists serving as the reference standard. The ability of the IDL model to improve performance of junior radiologists in measuring morphologic UIA features was assessed. Results The study included 1182 patients with UIAs and 578 controls without UIAs as the training dataset (55 years [IQR, 47-62], 1,012 [57.5%] females) and 535 patients with UIAs as the multicenter external testing set (57 years [IQR, 50-63], 353 [66.0%] females). The IDL model achieved 97% accuracy in detecting UIAs and achieved a DSC of 0.90 (95%CI, 0.88-0.92) for UIA segmentation. Model-based morphologic measurements showed good agreement with reference standard measurements (all ICCs > 0.85). Within the multicenter external testing set, the IDL model also showed agreement with reference standard measurements (all ICCs > 0.80). Junior radiologists assisted by the IDL model showed significantly improved performance in measuring UIA size (ICC improved from 0.88 [0.80-0.92] to 0.96 [0.92-0.97], P < .001). Conclusion The developed integrated deep learning model using CTA data showed good performance in UIA detection, segmentation and morphologic measurement and may be used to assist less experienced radiologists in morphologic analysis of UIAs. ©RSNA, 2024.

Outcomes and prognostic factors in pediatric orbital trapdoor fracture: a multi-center study.

To evaluate clinical presentations, computed tomography (CT) findings, and various prognostic factors affecting the surgical outcomes of trapdoor fractures. This retrospective multi-center study reviewed medical records and orbital CT scans of patients under 21 years old, diagnosed with isolated trapdoor fractures. The study was conducted across multiple medical centers, including emergency and clinical departments in Isfahan, Shiraz, and Tehran-Iran. The characteristics and outcomes following surgical intervention were assessed. 45 patients with isolated trapdoor fractures were included in the study, with a mean age of 11.67 ± 4.69 years, predominantly male (84.4%). Vehicle accidents was the major cause of fractures (31.1%). 44 patients (97.8%) had orbital floor fracture, and one patient (2.2%) had medial wall involvement. Nausea/vomiting were reported in 41 patients (91.1%). Surgical intervention within 2 days, resulted in 85.0% of patients experiencing no postoperative diplopia. Delayed surgery beyond 2 days showed increased odds of diplopia, although not statistically significant. CT scan findings suggested a lower risk of diplopia in patients with soft tissue entrapment compared to muscle involvement (OR: 0.336, 95% CI: 0.077-1.462, p = 0.146). Shorter time to surgery (within 2 days) was significantly associated with normal postoperative eye movements (p = 0.002). Nausea/vomiting were more prevalent in patients with muscle entrapment (p < 0.05). Surgical intervention within 48h is crucial for improving ocular motility following trapdoor fractures. Extraocular symptoms, including nausea/vomiting, should raise suspicion for trapdoor fractures in cases of orbital trauma associated with ocular movement impairment. Not applicable.