Clinical Classification Research Articles

The Impact of Symptomatic Chronic Venous Insufficiency (CVI) on Health-Related Quality of Life (HR Qol) in A Multi-Ethnics Society in a Developing Nation

INTRODUCTION: Chronic venous insufficiency (CVI) is a common condition especially among those of advance age that is often neglected. As the disease severity progresses, it increases the healthcare cost and resources required, while diminishing the quality of life of the persons. Health-related Quality of Life (HRQoL) among CVI patients begins to decline once the symptom starts to appear, and reduces it further as the symptoms worsens. MATERIALS AND METHODS: This is a prospective, multi-centred, cross-sectional study on consenting symptomatic CVI patients who presented to the International Islamic University of Malaysia (IIUM) teaching hospital in Pahang, Malaysia. The diagnosis of CVI was confirmed on duplex imaging. Clinical grading was performed using Clinical Etiologic Anatomic Pathophysiologic (CEAP) classification. Patients completed generic validated Malay language Short Form 36 (SF36) HRQoL instrument. RESULTS: One hundred and ten patients (62% male) with a mean age of 57 years, Malays (60%), Chinese (25%) and Indian (15%) were recruited. The most frequent CVD symptoms reported were pain (42%). The clinical, aetiological, anatomical, and pathophysiological (CEAP) classification placed most patients in the C2 class (34%). Apart from partaking in social functions, all other elements of mental and physical health component of SF 36 showed a marked deterioration as the disease progressed. CONCLUSIONS: We found a significant decline in the HRQoL among symptomatic CVI patients presenting to IIUM hospital in a multi-ethnic developing country.

Functional characterization of 2,832 JAG1 variants supports reclassification for Alagille syndrome and improves guidance for clinical variant interpretation

Pathogenic variants in the JAG1 gene are a primary cause of the multi-system disorder Alagille syndrome. Although variant detection rates are high for this disease, there is uncertainty associated with the classification of missense variants that leads to reduced diagnostic yield. Consequently, up to 85% of reported JAG1 missense variants have uncertain or conflicting classifications. We generated a library of 2,832 JAG1 nucleotide variants within exons 1-7, a region with a high number of reported missense variants, and designed a high-throughput assay to measure JAG1 membrane expression, a requirement for normal function. After calibration using a set of 175 known or predicted pathogenic and benign variants included within the variant library, 486 variants were characterized as functionally abnormal (n= 277 abnormal and n= 209 likely abnormal), of which 439 (90.3%) were missense. We identified divergent membrane expression occurring at specific residues, indicating that loss of the wild-type residue itself does not drive pathogenicity, a finding supported by structural modeling data and with broad implications for clinical variant classification both for Alagille syndrome and globally across other disease genes. Of 144 uncertain variants reported in patients undergoing clinical or research testing, 27 had functionally abnormal membrane expression, and inclusion of our data resulted in the reclassification of 26 to likely pathogenic. Functional evidence augments the classification of genomic variants, reducing uncertainty and improving diagnostics. Inclusion of this repository of functional evidence during JAG1 variant reclassification will significantly affect resolution of variant pathogenicity, making a critical impact on the molecular diagnosis of Alagille syndrome.

Mental Health Diagnoses Risk Among Children and Young Adults With Cerebral Palsy, Chronic Conditions, or Typical Development

Mental health (MH) issues in children with cerebral palsy (CP) are poorly understood compared with other pediatric populations. To examine MH diagnosis code assignment among children and young adults with CP and compare with typically developing (TD) and chronic condition (CC) pediatric populations. This case-control study used International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes to create a CP case set and CC and TD control sets using electronic health record data of children and young adults from a large tertiary care children's hospital in the midwestern United States between 2010 and 2022. Case-control matching was performed to control for demographic factors. Data were analyzed from June to December 2023. All MH diagnosis codes were mapped to ICD-10-CM and categorized using Clinical Classifications Software Refined (CCSR). The incidence rates of MH CCSR categories were calculated. Descriptive and comparative statistics were used to evaluate the significance and odds associated with factors. Data from 216 794 individuals (mean [SD] baseline age, 4.3 [5.1] years; 118 562 [55%] male) were analyzed, including 3544 individuals with CP, 142 160 individuals with CC, and 71 080 TD individuals. The CP cohort spread across Gross Motor Function Classification System (GMFCS) levels I (981 individuals [28%]), II (645 individuals [18%]), III (346 individuals [10%]), IV (502 individuals [14%]), and V (618 individuals [17%]). Rates varied significantly for anxiety (824 individuals with CP [23%]; 25 877 individuals with CC [9%]; 6274 individuals with TD [18%]), attention-deficit/hyperactivity disorder (534 individuals with CP [15%]; 22 426 individuals with CC [9%]; 6311 individuals with TD [16%]); conduct or impulse disorder (504 individuals with CP [14%]; 13 209 individuals with CC [5%]; 3715 individuals with TD [9%]), trauma or stress disorders (343 individuals with CP [10%]; 18 229 individuals with CC [8%]; 5329 individuals with TD [13%]), obsessive-compulsive disorder (251 individuals with CP [7%]; 3795 individuals with CC [1%]; 659 individuals with TD [3%]), depression (108 individuals with CP [3%]; 12 224 individuals with CC [5%]; 4007 individuals with TD [9%]), mood disorders (74 individuals with CP [2%]; 4355 individuals with CC [2%]; 1181 individuals with TD [3%]), and suicidal ideation (72 individuals with CP [2%]; 7422 individuals with CC [5%]; 3513 individuals with TD [5%]). There was significant variation in odds of MH diagnoses by GMFCS level (I-II vs III-V: odds ratio [OR], 1.23; 95% CI, 1.09-1.40; P = .001). Among individuals with CP, males were more likely than females to have diagnosis codes for conduct or impulse disorders (OR, 1.41; 95% CI, 1.16-1.73) and attention-deficit/hyperactivity disorder (OR, 1.41 [95% CI, 1.15-1.73]). Black individuals, compared with White individuals, were more likely to have diagnoses for obsessive-compulsive disorder (OR, 1.57 [95% CI, 1.14-2.16]), other mood disorders (OR, 1.85 [95% CI, 1.01-3.38]), and trauma or stress disorders (OR, 1.94 [95% CI, 1.44-2.63]). Odds for trauma or stress disorders were elevated for individuals who identified as other races compared with White individuals (OR, 2.80 [95% CI, 2.03-3.87]). In this case-control study of children and young adults with CP and matched comparisons, anxiety and conduct or impulse diagnoses were higher in individuals with CP. The lower diagnosis rates of depression and suicidal ideation may indicate underdiagnosis among individuals with CP. There is likely a need for assessment tools that are more suitable for children with CP.

Genotype and Phenotype Correlation of Patients with Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is the most common inherited connective tissue disease of the bone, characterized by recurrent fractures and deformities. In patients displaying the OI phenotype, genotype-phenotype correlation is used to screen multiple genes swiftly, identify new variants, and distinguish between differential diagnoses and mild subtypes. This study evaluated variants identified through next-generation sequencing in 58 patients with clinical characteristics indicative of OI. The cohort included 18 adults, 37 children, and 3 fetuses. Clinical classification revealed 25 patients as OI type I, three patients as OI type II, 18 as OI type III, and 10 as OI type IV. Fifteen variants in COL1A1 were detected in 19 patients, 9 variants in COL1A2 (n=19), 5 variants in LEPRE1/P3H1 (n=7), 3 variants in FKBP10 (n=4), 3 variants in SERPINH1 (n=2), 1 variant in IFITM5 (n=1), and 1 variant in PLS3 (n=1). In total, 37 variants (18 pathogenic, 14 likely pathogenic, and 5 variants of uncertain significance), including 16 novel variants, were identified in 43 (37 probands, 6 family members) of the 58 patients analyzed. This study highlights the efficacy of panel testing in the molecular diagnosis of OI, the significance of the next-generation sequencing technique, and the importance of genotype-phenotype correlation.

A Comparison of Variable Input Strategies used for Risk-adjustment Models of Antimicrobial Use

Background: External comparisons of antimicrobial use (AU) may be more informative if adjusted for encounter characteristics. Optimal methods to define input variables for encounter-level risk-adjustment models of AU are not established. Methods: This retrospective analysis of electronic health record data included 50 US hospitals in 2020-2021. We used NHSN definitions for all antibacterials days of therapy (DOT), including adult and pediatric encounters with at least 1 day present in inpatient locations. We assessed 4 methods to define input variables: 1) diagnosis-related group (DRG) categories by Yu et al., 2) adjudicated Elixhauser comorbidity categories by Goodman et al., 3) all Clinical Classification Software Refined (CCSR) diagnosis and procedure categories, and 4) adjudicated CCSR categories where codes not appropriate for AU risk-adjustment were excluded by expert consensus, requiring review of 867 codes over 4 months to attain consensus. Data were split randomly, stratified by bed size as follows: 1) training dataset including two-thirds of encounters among two-thirds of hospitals; 2) internal testing set including one-third of encounters within training hospitals, and 3) external testing set including the remaining one-third of hospitals. We used a gradient-boosted machine (GBM) tree-based model and two-staged approach to first identify encounters with zero DOT, then estimate DOT among those with >0.5 probability of receiving antibiotics. Accuracy was assessed using mean absolute error (MAE) in testing datasets. Correlation plots compared model estimates and observed DOT among testing datasets. The top 20 most influential variables were defined using modeled variable importance. Results: Our datasets included 629,445 training, 314,971 internal testing, and 419,109 external testing encounters. Demographic data included 41% male, 59% non-Hispanic White, 25% non-Hispanic Black, 9% Hispanic, and 5% pediatric encounters. DRG was missing in 29% of encounters. MAE was lower in pediatrics as compared to adults, and lowest for models incorporating CCSR inputs (Figure 1). Performance in internal and external testing was similar, though Goodman/Elixhauser variable strategies were less accurate in external testing and underestimated long DOT outliers (Figure 2). Agnostic and adjudicated CCSR model estimates were highly correlated; their influential variables lists were similar (Figure 3). Conclusion: Larger numbers of CCSR diagnosis and procedure inputs improved risk-adjustment model accuracy compared with prior strategies. Variable importance and accuracy were similar for agnostic and adjudicated approaches. However, maintaining adjudications by experts would require significant time and potentially introduce personal bias. If findings are confirmed, the need for expert adjudication of input variables should be reconsidered.Disclosure: Elizabeth Dodds Ashley: Advisor- HealthTrackRx. David J Weber: Consultant on vaccines: Pfizer; DSMB chair: GSK; Consultant on disinfection: BD, GAMA, PDI, Germitec

Utilisation of Atlanta Classification for Local Complications and Severity Detection of Acute Pancreatitis – A Narrative Review

Abstract Acute pancreatitis (AP) is one of the most common acute abdominal pathologies, having varying grades of severity and presentation ranging from mild self-limiting pain in the abdomen and vomiting to severe category which consists of multiple organ failure, sepsis, fever, and severe abdominal pain and vomiting making the patient hospital-bound. Over the years, many radiological and clinical classification systems have emerged to categorize the patient severity and associated local complications to assess their prognosis and help the clinicians decide the treatment plan. Patients suffering from mild pancreatitis are treated with conservative management, whereas those with moderate-to-severe pancreatitis are dealt with minimally invasive or surgical procedures hence making it necessary to classify the patients according to their severity which further helps the clinicians and surgeons decide on treatment plans. The revised Atlanta’s (2012) classification has made a milestone change in the way we classify AP and its complications by including the presence of organ failure and local fluid collections as an essential component of severity grading. In this review article, we will be reviewing past literature and discussing the efficacy of the revised Atlanta classification (2012) in evaluating the type of pancreatitis, the presence or absence of organ failure, local complications, and its role in assessing the prognosis of the patient.

An analysis of potentially avoidable neurosurgical transfers to a tertiary-care level I trauma center.

Previous studies of neurosurgical transfers indicate that substantial numbers of patients may not need to be transferred, suggesting an opportunity to provide more patient-centered care by treating patients in their communities, while probably saving thousands of dollars in transport and duplicative workup. This study of neurosurgical transfers, the largest to date, aimed to better characterize how often transfers were potentially avoidable and which patient factors might affect whether transfer is needed. This was a retrospective cohort study of neurosurgical transfers to an urban, tertiary-care, level I trauma center between October 1, 2017, and October 1, 2022. Prior to data analysis, the authors devised criteria to differentiate necessary neurosurgical transfers from potentially avoidable ones. A transfer was considered necessary if 1) the patient went to the operating room within 12 hours of arrival at the emergency department (ED); 2) a neurological MRI study was conducted in the ED; 3) the patient was admitted to the ICU from the ED; or 4) the patient was admitted to either neurology or a surgical service (including neurosurgery). Transfers not meeting any of the above criteria were deemed potentially avoidable. Patient and clinical characteristics, including diagnostic groupings from Clinical Classification Software categories, were collected retrospectively via electronic health record data abstraction and stratified by whether the transfer was necessary or potentially avoidable. Statistical differences were assessed with a chi-square test. A total of 5113 neurosurgical transfers were included in the study, of which 1701 (33.3%) were classified as potentially avoidable. Four percent of all transferred patients went to the operating room within 12 hours of reaching the receiving ED, 23.4% were admitted to the ICU from the ED, 26.6% had a neurological MRI study performed in the ED, and 54.4% were admitted to a surgical service or to neurology. Potentially avoidable transfers had a higher proportion of traumatic brain injury, headache, and syncope (p < 0.0001), as well as of spondylopathies/spondyloarthropathies (p = 0.0402), whereas patients needing transfer had a higher proportion of acute hemorrhagic cerebrovascular disease and cerebral infarction (p < 0.0001). This study demonstrates that a large number of neurosurgical transfers can probably be treated in their home hospitals and highlights that the vast majority of patients transferred for neurosurgical conditions do not receive emergency neurosurgery. Further research is needed to better guide transferring and receiving facilities in reducing the burden of excessive transfers.

SARS-CoV-2 antigenemia and RNAemia in association with disease severity in patients with COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, causes a spectrum of symptoms ranging from mild upper to severe lower respiratory tract infections. However, the dynamics of nucleocapsid (N) protein antigenemia and RNAemia are not fully understood. We conducted a cohort study involving 117 patients with clinically confirmed COVID-19, focusing on the kinetics of antigenemia and RNAemia and their association with various clinical characteristics. The patients had a median age of 66.0 years (52.0–79.0 years), with a gender distribution of 46.2% male and 53.8% female. Antigenemia reached 100% in fatal cases during the first week after admission. The sensitivity/specificity of antigenemia for diagnosis were 64.7%/73.0% at admission, 69.1%/100% in Week 1, and 66.3%/100% in Week 2. Additionally, the rates of antigenemia in asymptomatic patients were 27.3% upon admission and 22.0% in Week 1, respectively; however, no antigenemia was in samples collected in Week 2. Viral RNAemia was not detected in asymptomatic patients, but RNAemia viral loads were elevated in fatal cases. Kaplan–Meier survival curves demonstrated a higher mortality rate when antigenemia concentrations were elevated in the follow-up samples (P = 0.005). Our study provides a comprehensive analysis of the kinetics of viral N-protein antigenemia and RNAemia according to disease severity and clinical classification. Our findings suggest that highest concentrations of antigenemia in fatal cases occur in the first week after admission, indicating that early elevated antigenemia may serve as a marker of mortality risk.

Fully Integrated and High-Throughput Microfluidic System for Multiplexed Point-Of-Care Testing.

For every epidemic outbreak, the prevention and treatments in resource-limited areas are always out of reach. Critical to this is that high accuracy, stability, and more comprehensive analytical techniques always rely on expensive and bulky instruments and large laboratories. Here, a fully integrated and high-throughput microfluidic system is proposed for ultra-multiple point-of-care immunoassay, termed Dac system. Specifically, the Dac system only requires a handheld portable device to automatically recycle repetitive multi-step reactions including on-demand liquid releasing, dispensing, metering, collecting, oscillatory mixing, and discharging. The Dac system performs high-precision enzyme-linked immunosorbentassays for up to 17 samples or targets simultaneously on a single chip. Furthermore, reagent consumption is only 2% compared to conventional ELISA, and microbubble-accelerated reactions shorten the assay time by more than half. As a proof of concept, the multiplexed detections are achieved by detecting at least four infection targets for two samples simultaneously on a singular chip. Furthermore, the barcode-based multi-target results can rapidly distinguish between five similar cases, allowing for accurate therapeutic interventions. Compared to bulky clinical instruments, the accuracy of clinical inflammation classification is 92.38% (n = 105), with a quantitative correlation coefficient of R2 = 0.9838, while the clinical specificity is 100% and the sensitivity is 98.93%.

Retinal Map of Peripheral Retinal Degenerations and Tears. Part 1. Non­-Regmatogenous Intraretinal Degenerations of the Retina

The aim of the article is to develop a clinical classification and an informative retinal map of peripheral degenerations and retinal tears based on multimodal diagnostics of the vitreoretinal interface.Methods. Multimodal studies of patients with peripheral degenerations included traditional and additional techniques: the ultra­wide­angle fundus imaging with the Clarus 500 camera and wide­field OCT Line scanning using the “sliding method”. .Results. During the period 2014–2024, 1304 peripheral degenerations and retinal tears were identified through the multimodal examination of 614 patients (959 eyes). Based on these studies, a clinical and topographic classification of peripheral degenerations and retinal tears is presented.Conclusion. Multimodal studies has facilitated the creation of a retinal map of the most common peripheral degenerations and retinal tears, the potential to improve the timely recognition of vitreoretinal pathology and optimize treatment tactics.

Aggressive Periodontitis: A case report with exome sequencing and functional characterization of identified variant

Aggressive periodontitis (AgP) is characterized by rapid and progressive destruction of the periodontal tissues and eventual tooth loss. Genetic risk contributions have been explored and rare mutations in NOD2 were reported. Sequencing analysis of the coding regions of NOD2 was conducted using individuals of African ancestry, to identify the pathogenic protein-altering variants in individuals with AgP using: 1) In Silico tools and clinical variant classification system; 2) IF staining to understand the expression pattern, and 3) In vitro cell based assay to understand the variant protein function. We discovered a novel nonsense NOD2 variant (c.835G&gt;T; p.Glu279Ter) ; a truncating protein variant that is clinically pathogenic, and the gene-product lacks domains regulating inflammatory responses. Murine studies suggest that this gene contributes to tooth development. In vitro analysis suggests a dominant-negative effect of the variant. NOD2 gene is expressed in the immune cells and periodontal tissues and regulates the inflammatory response within this tissue. This truncating variant found in one African family, which results in a dominant-negative effect, could explain the exacerbated immune response to pathogens in the pathogenesis of this periodontal disease.

Comparison of the Transcranial Approach and Transsphenoidal Approach Based on the Anatomical Location of Origin in Pediatric Craniopharyngiomas

BackgroundVarious clinical classifications of craniopharyngiomas (CRPs) have been proposed to suggest optimal surgical planning. We aimed to evaluate the clinical outcomes of pediatric CRPs and the clinical significance of anatomical classification in relation to the diaphragm sellae. MethodsA retrospective review was conducted on patients under 18 years of age who underwent surgery for CRPs from July 1998 to August 2022. The patients were divided into transcranial approach (TCA), and transsphenoidal approach (TSA) groups, which included microscopic TSA and endoscopic endonasal approach (EEA) groups. EEA has been adopted at our institute since 2011. CRPs were classified by their origin and relationship with the diaphragm sellae. ResultsA total of 132 pediatric CRP patients were included in this study, 117 of whom underwent surgery for primary CRP and 15 for recurrent CRP. Among them, 89 (67.4%) underwent TCA, 9 (6.8%) had microscopic TSA, and 34 (25.8%) had EEA. In subdiaphragmatic CRPs with competent diaphragm sellae, TSA tended to yield better outcomes than did TCA in terms of stalk preservation and ophthalmological outcomes. After the introduction of EEA, the proportion of supradiaphragmatic CRPs treated via the TSA increased from 0% to 50% (p < 0.001). Gross total resection (HR=0.194; 95% CI=0.102–0.367, p < 0.001) and adjuvant therapy (HR=0.208; 95% CI=0.048–0.897, p = 0.035) were found to be positive prognostic factors for long-term tumor control. ConclusionsOver time, with the adoption of EEA at our institute, the impact of anatomical classification on the surgical apprpoach has decreased. Nevertheless, an individualized surgical approach should be employed to improve long-term outcomes and minimize complications for pediatric CRPs.

Radiofrequency echographic multi-spectrometry-based measurement of bone mineral density in patients with severe motor and intellectual disability: An opportunity for patients with severe scoliosis and hip dislocation

PurposeRadiofrequency echographic multi-spectrometry (REMS) is an ultrasound technology currently used for the densitometric evaluation of osteoporosis and has been validated against dual-energy X-ray absorptiometry. However, the use of REMS for bone densitometry in patients with severe motor and intellectual disabilities (SMID) remains to be reported. This study aimed to investigate whether REMS technology can be used for densitometric evaluation of osteoporosis in patients with SMID with hip dislocation and severe scoliosis. MethodsSixty-five patients with SMID, who resided in a long-term care facility and received comprehensive medical and rehabilitation care, underwent REMS scans of the femoral neck and/or lumbar spine. Data regarding anthropometric parameters (height and weight), bone mineral density (BMD), clinical diagnostic classification, physical ability, presence of scoliosis and hip dislocation, and frontal radiographs of both hip joints were obtained. ResultsWe included 29 men and 34 women (mean age: 52.6 years). All patients underwent successful scanning at either the femoral neck (82.5 %) or lumbar spine (95.2 %). BMD measurements obtained using REMS revealed low values, with a mean BMD, T-score, and Z-score of 0.67 g/cm2, −2.39 standard deviation (SD), and − 1.38 SD, respectively, at the femoral neck and 0.66 g/cm2, −2.70 SD, and − 1.87 SD, respectively, at the lumbar spine. The average Cobb angle of the lumbar spine was 34.0°; furthermore, dislocation rates did not significantly differ between those with and without successful BMD measurements (p = 0.073). Lumbar BMD T-scores were significantly correlated with femoral neck BMD T-scores (p < 0.001, r = 0.530). ConclusionAll patients with SMID were able to undergo measurements of either spinal or femoral neck BMD; furthermore, 77.7 % of the patients underwent measurements at both the lumbar spine and femur. Our data suggest that REMS is useful for measuring BMD in patients with SMID who are residing in institutions.

Analysis of clinical and genetic characteristics of the severe liver disease phenotype in patients with hepatolenticular degeneration

Objective: To investigate the clinical and genetic characteristics and predictive role of the severe liver disease phenotype in patients with hepatolenticular degeneration (HLD). Methods: Inpatients with HLD confirmed at Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine from January 1989 to December 2022 were selected as the research subjects. Clinical classification was performed according to the affected organs. Patients with liver disease phenotypes were classified into the liver disease group and further divided into the severe liver disease group and the ordinary liver disease group. The clinical characteristics and genetic variations were compared in each group of patients. The predictive indicators of patients with severe liver disease were analyzed by multiple regression. Statistical analysis was performed using the t-test, Mann-Whitney U test, or χ(2) test according to different data. Results: Of the 159 HLD cases, 142 were in the liver disease group (34 in the severe liver disease group and 108 in the ordinary liver disease group), and 17 were in the encephalopathy group. The median age of onset was statistically significantly different between the liver disease group and the encephalopathy group [12.6 (7.0, 13.3) years versus 16.9 (11.0, 21.5) years, P<0.01]. 156 ATP7B gene mutation sites were found in 83 cases with genetic testing results, of which 54 cases carried the p.Arg778Leu gene mutation (allele frequency 46.2%). Compared with patients with other types of gene mutations (n=65), patients with homozygous p.Arg778Leu mutations (n=18) had lower blood ceruloplasmin and albumin levels, a higher prognostic index, Child-Pugh score, an international normalized ratio, and prothrombin time (P<0.05). Hemolytic anemia, corneal K-F ring, homozygous p.Arg778Leu mutation, and multiple laboratory indexes in the severe liver disease group were statistically significantly different from those in the ordinary liver disease group (P<0.05). Multivariate logistic regression analysis showed that the predictive factors for severe liver disease were homozygous p.Arg778Leu mutation, total bilirubin, and bile acids (ORs=16.512, 1.022, 1.021, 95% CI: 1.204-226.425, 1.005-1.039, and 1.006-1.037, respectively, P<0.05). The drawn ROC curve demonstrated a cutoff value of 0.215 3, an AUC of 0.953 2, and sensitivity and specificity of 90.91% and 92.42%, respectively. Conclusion: Liver disease phenotypes are common in HLD patients and have an early onset. Total bilirubin, bile acids, and the homozygous p.Arg778Leu mutation of ATP7B is related to the severity of liver disease in HLD patients, which aids in predicting the occurrence and risk of severe liver disease.

MDB-11. DOES THE INTRAOPERATIVE ASSESSMENT OF SITE OF ORIGIN OF MEDULLOBLASTOMA ALLOW FOR A TAILORING OF THE NEUROSURGICAL STRATEGY? DATA FROM A RETROSPECTIVE SINGLE-CENTER ASSESSMENT AND PROPOSAL OF A PROSPECTIVE MULTICENTER STUDY

Abstract BACKGROUND Developmental gene expression data from medulloblastoma (MB) suggest that WNT-MB originate from the region of the embryonic lower rhombic lip (LRL), whereas SHH-MB and non-WNT/non-SHH MB arise from cerebellar precursor matrix regions. This study aims to analyze detailed intraoperative data with regard to the site of origin (STO) and compare these findings with the hypothesized regions of origin associated with the molecular group. METHODS A review of the institutional database identified 58 out of 72 pediatric patients who were operated on a MB at our department between 1996 and 2020 that had a detailed operative report, surgical video as well as clinical and genetic classification data available for analysis. The STO was assessed based on intraoperative findings. RESULTS Using the intraoperatively defined STO, “correct” prediction of molecular groups was feasible in 20% of WNT-MB, 60% of SHH-MB and 71% of non-WNT/non-SHH MB. The positive predictive values of the neurosurgical inspection to detect the molecular group were 0.21 (95% CI 0.08–0.48) for WNT-MB, 0.86 (95% CI 0.49–0.97) for SHH-MB and 0.73 (95% CI 0.57–0.85) for non-WNT/non-SHH MB. CONCLUSION In our series of 58 well-documented cases, the intraoperative assessment of the STO could not reliably predict the molecular group. Thus, the current evidence does still not allow for intraoperative group-specific risk stratification that would enable tailoring the neurosurgical strategy to the prognostic and predictive profile of the patient. Prospective multicenter assessments are necessary to systematically evaluate the growth pattern and site of origin of medulloblastoma. Accordingly, a study protocol of an international cohort study will be presented.

Robust brain tumor classification by fusion of deep learning and channel-wise attention mode approach

Diagnosing brain tumors is a complex and time-consuming process that relies heavily on radiologists’ expertise and interpretive skills. However, the advent of deep learning methodologies has revolutionized the field, offering more accurate and efficient assessments. Attention-based models have emerged as promising tools, focusing on salient features within complex medical imaging data. However, the precise impact of different attention mechanisms, such as channel-wise, spatial, or combined attention within the Channel-wise Attention Mode (CWAM), for brain tumor classification remains relatively unexplored. This study aims to address this gap by leveraging the power of ResNet101 coupled with CWAM (ResNet101-CWAM) for brain tumor classification. The results show that ResNet101-CWAM surpassed conventional deep learning classification methods like ConvNet, achieving exceptional performance metrics of 99.83% accuracy, 99.21% recall, 99.01% precision, 99.27% F1-score and 99.16% AUC on the same dataset. This enhanced capability holds significant implications for clinical decision-making, as accurate and efficient brain tumor classification is crucial for guiding treatment strategies and improving patient outcomes. Integrating ResNet101-CWAM into existing brain classification software platforms is a crucial step towards enhancing diagnostic accuracy and streamlining clinical workflows for physicians.

Dislodged Endovascular Heat-induced Thrombus Resulting in Pulmonary Embolus Following Postoperative Ultrasound Compression

Venous insufficiency and consequent varicose veins are common problems faced by many patients. Fortunately, there are many treatment options available including a minimally invasive method known as radiofrequency ablation (RFA). Radiofrequency ablation is not without complications; among those are endovascular heat-induced thrombosis (EHIT). This rare complication is typically managed conservatively; however, in rare occasions, the thrombus can detach and embolize causing further issues for patients. A 48-year-old male underwent an uneventful RFA procedure for a Clinical Etiologic Anatomic Pathophysiologic classification (CEAP) 4a venous insufficiency. On the postoperative ultrasound (US) venous duplex evaluation, the patient was found to have EHIT type 1 in the right greater saphenous vein extending to the sapheno-femoral junction. During compression and release of the US probe by the US technologist the thrombus detached from the venous wall and embolized to a right lung subsegmental branch. This case report focuses on the possibility of secondary sequela that may arise from EHIT affecting other organ systems from the RFA procedure, the classification system of EHIT, and management options.

Noninvasive identification and therapeutic implications of supernormal left ventricular contractile phenotype

Left ventricular (LV) function is typically evaluated through LV ejection fraction (EF), a robust indicator of risk, showing a nonlinear increase in mortality rates below 40%. Conversely, excessively high EF values (&gt; 65%) also correlate with elevated mortality, following a U-shaped curve, with its nadir observed between 50% and 65%. This underscores the necessity for improved identification of the hypercontractile phenotype. However, EF is not synonymous with LV contraction function, as it can fluctuate independently of contractility due to variations in afterload, preload, heart rate, and ventricular-arterial coupling. Assessing the contractile status of the LV requires more specific metrics, such as LV elastance (or contractile force) and global longitudinal strain. Current guidelines outline various parameters for a more precise characterization of LV contractility, yet further research is warranted for validation. The true hypercontractile phenotype is evident in cardiac pathologies such as hypertrophic cardiomyopathy, ischemia with angiographically normal coronary arteries, Tako-tsubo syndrome, heart failure with preserved EF, and may also stem from systemic disorders including anemia, hyperthyroidism, liver, kidney, or pulmonary diseases. The hypercontractile phenotype constitutes a distinctive hemodynamic substrate underlying clinical manifestations such as angina, dyspnea, or arrhythmias, presenting a target for intervention through beta-blockers or specific cardiac myosin inhibitors. While EF remains pivotal for clinical classification, risk stratification, and therapeutic decision-making, integrating it with other indices of LV function can enhance the characterization of the hypercontractile phenotype.

Incremental Societal Costs of Perioperative Complications Following Adult Elective Inpatient Major Therapeutic Surgery in the State of Florida: A Seven-Year Retrospective Epidemiological Analysis.

Introduction There is an expanding role for anesthesiologists in the preoperative optimization and postoperative management of patients, often in the context of a so-called perioperative surgical home. Such efforts typically include enhanced recovery after surgery (ERAS) protocols and often an anesthesiologist-led team for perioperative management. Studies of the cost-effectiveness of such approaches have generally been conducted at single institutions, with most patients cared for by small numbers of surgeons. This limitation creates generalizability issues as to whether improvement was related mostly to organizational culture or the studied surgeons' practices (non-generalizable) versusthe procedures (generalizable). We studied whether other organizations can rely on achieving similar benefits following the adoption of a studied process improvement strategy at a single institution. Methods All patients undergoing elective major therapeutic inpatient surgery discharged between October 2015 and June 2022 at non-federal hospitals in the state of Florida were included. For each discharge, the United States Medicare Severity Diagnosis-Related Group (MS-DRG) weighting factor (i.e., the multiplier for the hospital's base rate for admissions that determines reimbursement) and the Clinical Classification Software Refined (CCSR) code for the principal procedure were determined at admission and discharge from the state's inpatient healthcare database based on the diagnoses present at those time points. An increase in the weighting factor from admission to discharge represents societal costs from perioperative complications. Statewide, by hospital, and by surgeon, we calculated the total increase for each CCSR's weighting factor. Our primary hypothesis was that surgeon variability would be statistically greater than CCSR variability but that the incremental effect would be <5%. If CCSR and surgeon variability were comparable, this would be supportive of generalizability. In contrast, if there were a predominant effectrelated to the surgeon, results from one institution might not be applicable to others. Results Among the 1,482,344 discharges studied, the pooled (N=7 years) contributions to MS-DRG weighting factor increases from the upper 20% of surgeons were 2.8% more than from the upper 20% of CCSRs (95% CI 1.9%-3.9%, p=0.0006). Those CCSRs accounted for 85.5% (95% CI 79.4%-91.7%, p<0.0001) of the total increase in the MS-DRG weighting factor. The average contribution of the top two surgeons at each hospital to that hospital's increase in the weighting factor ranged among CCSRs from 68% to 97%.The median and 75th percentile of surgeons performing at least 10% of the total number of cases at each hospital was similar to those values for the contributions to the increases in the MS-DRG weighting factor, median 2.0 to 3.0, and 75th percentile 1.75 to 4.0. Conclusions Because variability among surgeons in their contributions to increases in the MS-DRG weighting factor only slightly exceeded the variability among CCSR surgical categories, perioperative surgical home and ERAS study research results involving single institutions and a small number of surgeons would likely be generalizable to other hospitals and healthcare systems. Funding agencies should not be hesitant to fund single-center perioperative surgical home studiesand ERAS interventions based on concerns related to lack of generalizability.

The burden of readmissions after rib fractures among older adults

BackgroundThe index hospitalization morbidity and mortality of rib fractures among older adults (aged ≥65 years) is well-known, yet the burden and risks for readmissions after rib fractures in this vulnerable population remain understudied. We aimed to characterize the burdens and etiologies associated with 3-month readmissions among older adults who suffer rib fractures. We hypothesized that readmissions would be common and associated with modifiable etiologies. MethodsThis survey-weighted retrospective study using the 2017 and 2019 National Readmissions Database evaluated adults aged ≥65 years hospitalized with multiple rib fractures and without major extrathoracic injuries. The main outcome was the proportion of patients experiencing all-cause 3-month readmissions. We assessed the 5 leading principal readmission diagnoses overall and delineated them by index hospitalization discharge disposition (home or facility). Sensitivity analysis using clinical classification categories characterized readmissions that could reasonably represent rib fracture-related sequelae. ResultsIn 2017, 25,092 patients met the inclusion criteria, with 20% (N = 4,894) experiencing 3-month readmissions. Six percent of patients did not survive their readmission. The 5 leading principal readmission diagnoses were sepsis (many associated with secondary diagnoses of pneumonia [41%] or urinary tract infections [41%]), hypertensive heart/kidney disease, hemothorax, pneumonia, and respiratory failure. In 2019, a comparable 3-month readmission rate of 23% and identical 5 leading diagnoses were found. Principal readmission diagnosis of hemothorax was associated with the shortest time to readmission (median [interquartile range]:9 [5–23] days). Among patients discharged home after index hospitalization, pleural effusion–possibly representing mischaracterized hemothorax–was among the leading principal readmission diagnoses. Some patients readmitted with a principal diagnosis of hemothorax or pleural effusion had these diagnoses at index hospitalization; a lower proportion of these patients underwent pleural fluid intervention during index hospitalization compared with readmission. On sensitivity analysis, 30% of 3-month readmissions were associated with principal diagnoses suggesting rib fracture-related sequelae. ConclusionReadmissions are not infrequent among older adults who suffer rib fractures, even in the absence of major extrathoracic injuries. Future studies should better characterize how specific complications associated with readmissions, such as pneumonia, urinary tract infections, and delayed hemothoraces, could be mitigated.