Severe Grade Research Articles

Prevalence and Demographic Correlates of Social Anxiety Disorder among Medical Students at Sultan Qaboos University: A Cross-sectional Study

Introduction and Objective: Social anxiety disorder (SAD) is an excessive and irrational fear of social situations, leading to an avoidance of those situations. Individuals with SAD may fear acting in a certain way or exhibiting anxiety symptoms in front of others, which can significantly impact their daily functioning and quality of life. Among medical students, SAD can negatively influence academic performance, particularly in exams, and lead to employment difficulties. The COVID-19 pandemic introduced unique stressors, including social isolation and the transition to online learning, which may have exacerbated anxiety-related conditions. Understanding the prevalence and associated factors of SAD during this period is essential to develop targeted interventions for students. Thus, this work aimed to assess the prevalence and demographic correlates of SAD among medical students at the College of Medicine and Health Sciences at Sultan Qaboos University (SQU) in Oman during the pandemic. Methods: A questionnaire-based cross-sectional study was conducted from September to October 2020 in SQU, College of Medicine and Health Sciences. Medical students from all academic years were invited to complete demographic data and the Liebowitz social anxiety scale (LSAS). The LSAS is a 24-item self-rating scale to assess SAD. An analysis using a Chi-square test was performed to obtain the factors associated with SAD. Results: A total of 558 students completed the questionnaire, of which 348 were female (62%). The total prevalence of SAD was 64%, whereas moderate grade SAD accounted for 27% of the participants, marked grade 19%, severe grade 11%, and very severe grade 7%. Among the students who had the disorder, 71% suffered a generalized subtype of SAD. A significant association between SAD and phase of study (p<0.001), age group (p<0.001), and gender (p<0.001) was found. Phase 1 (69%) exhibited the highest prevalence, followed by phase 2 (66%) and phase 3 (48%). Among the age groups, 17-19 years group (67%) demonstrated the highest prevalence, followed by age groups 20-22 (64%) and 23-25 (46%). In terms of gender, females (70%) were more likely to display SAD symptoms than males (52%). Conclusion: The results of this study indicated a high prevalence of SAD among medical students and showed a significant association between SAD and the phase of study, age group, and gender. These results could help justify the establishment of targeted mental health interventions to support medical students in managing their anxiety, which can ultimately result in an improvement in their academic performance and overall quality of life. University administrators and psychologists should aim to develop supportive programs for students.

Comparison of Tissue-Engineered Dermis with Micronized Adipose Tissue and Artificial Dermis for Facial Reconstruction Following Skin Cancer Resection

Our group has previously demonstrated that tissue-engineered dermis containing cultured fibroblasts or adipose-derived stromal vascular fraction cells is superior to artificial dermis in terms of scar quality for covering facial defects. However, using these cells for clinical applications requires Food and Drug Administration approval and involves complex procedures for cell culture or isolation. This retrospective study aimed to compare effects of tissue-engineered dermis containing micronized adipose tissue (MAT) and artificial dermis for facial reconstruction. Tissue-engineered dermis consisting of MAT seeded on artificial dermis was applied in 30 cases, while artificial dermis without MAT was grafted in 35 cases. Healing time and severities of scar contraction, color mismatch, and landmark distortion at one year after healing were evaluated. Wounds in the tissue-engineered dermis group re-epithelialized in 30.0 ± 4.3 days compared to 34.3 ± 5.4 days in the artificial dermis group (p < 0.05). The average dE2000 score in color mismatch analysis was 4.9 ± 1.7 in the tissue-engineered dermis group and 5.1 ± 1.7 in the artificial dermis group (p = 0.57). The extent of scar contraction was 16.2 ± 12.3% in the tissue-engineered dermis group and 23.2 ± 12.8% in the artificial dermis group (p < 0.05). The average severity grade of landmark distortion was 0.20 ± 0.50 in the tissue-engineered dermis group and 0.50 ± 0.71 in the artificial dermis group (p < 0.05). These findings indicate that tissue-engineered dermis grafts containing MAT are superior to artificial dermis grafts for facial reconstruction in terms of healing time, scar contraction, and landmark distortion severity. However, there was no significant difference in color mismatch between the two groups.

The value of hippocampal sub-region imaging features for the diagnosis and severity grading of ASD in children

BackgroundHippocampal structural changes in Autism Spectrum Disorder (ASD) are inconsistent. This study investigates hippocampal subregion changes in ASD patients to reveal intrinsic hippocampal anomalies. MethodsA retrospective study from Hainan Children’s Hospital database (2020–2023) included ASD patients and matched controls. We classified ASD participants based on severity, dividing all subjects into four groups: normal, mild, moderate, and severe. High-resolution T1-weighted MRI images were analyzed for hippocampal subregion segmentation and volume calculations using Freesurfer. Texture features were extracted via the Gray-Level Co-occurrence Matrix. The Receiver Operating Characteristic curve was used to evaluate seven random forest predictive models constructed from volume, subregion, and texture features, as well as their combinations following feature selection. ResultsThe study included 114 ASD patients (98 boys, 2–8 years; 16 girls, 2–6 years; 17 mild, 57 moderate, 40 severe) and 111 healthy controls (HCs). No significant differences in volumes were found between ASD patients and HCs (adjusted P-value >0.05). The seven random forest models showed that single volume and texture features performed poorly for ASD classification; however, integrating various feature types improved AUC values. Further selection of texture, subregion, and volume features enhanced AUC performance across normal and varying severity categories, demonstrating the potential value of specific subregions and integrated features in ASD diagnosis. ConclusionRandom forest models revealed that hippocampal volume, texture features, and subregion characteristics are crucial for diagnosing and assessing the severity of ASD. Integrating selected texture and subregion features optimized diagnostic efficacy, while combining texture, subregion, and volume features further improved severity grading effectiveness.

Incidence and Risk of Thromboembolic and Cardiovascular Adverse Events with PARP Inhibitor Treatment in Patients with Metastatic Castration-resistant Prostate Cancer: A Systematic Review and Safety Meta-analysis.

PARP inhibitor (PARPi) treatment is an effective option for patients with metastatic castration-resistant prostate cancer (mCRPC). There are few data on the cardiovascular and thromboembolic safety of these agents in mCRPC, as cardiovascular and thromboembolic adverse events (AEs) are uncommon. Our aim was to analyze the incidence and risk of major adverse cardiovascular events (MACEs), thromboembolic events, and hypertension with PARPi therapy in mCRPC. We conducted a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We systematically searched the PubMed, EMBASE, and Cochrane databases and the American Society of Clinical Oncology and European Society of Medical Oncology meeting abstracts for clinical trials on PARPi use in mCRPC up to March 31, 2024. We analyzed the pooled incidence of all-grade and high-grade MACEs, thromboembolic events, and hypertension, and calculated risk ratios (RRs) for PARPi versus non-PARPi treatment. We included 11 phase 2 or 3 trials in our meta-analysis. Hypertension was the most common AE for both any-grade (17.2%) and high-grade (9.3%) events. In comparison to other treatments, PARPi was associated with significantly higher risk of high-grade MACEs (RR 2.03; p=0.03) and thromboembolic events (RR 2.15; p=0.002), especially venous thromboembolism (VTE; RR 2.13; p=0.004) and pulmonary embolism (RR 3.60; p=0.001). The risk of hypertension, any-grade MACEs, and thromboembolic AEs was not significantly higher, apart from VTE (RR 2.17; p=0.01). There is higher risk of high-grade cardiovascular and thromboembolic toxicity with PARPi use in comparison to other treatments in mCRPC, although these toxicities are rare. Clinicians should be aware of this risk, especially in a population that often has comorbidities and concomitant treatments, for correct monitoring and management of these AEs. Drugs called PARP inhibitors are very effective in the treatment of metastatic prostate cancer that does not respond to hormone treatment. However, their use is associated with some cardiovascular adverse events, although these are rare. Our study shows that these events seem to be more frequent with PARP inhibitors than with other treatments, especially for severe grades. Doctors and patients should be aware of this risk to help in preventing, recognizing, and managing the occurrence of these rare complications.

Wheat Fusarium head blight severity grading using generative adversarial networks and semi-supervised segmentation

Wheat Fusarium head blight severity grading using generative adversarial networks and semi-supervised segmentation

Clinico-epidemiological profile of children with atopic dermatitis

Objectives: This study was conducted to assess clinico-epidemiological features of atopic dermatitis (AD) in children and evaluate disease severity using the SCORing atopic dermatitis index (SCORAD Index). Material and Methods: This was a hospital-based cross-sectional study carried out at the department of Dermatology at a tertiary care centre in North India over a period of 1 year. This study enrolled children aged between 3 months and 16 years of age clinically diagnosed with AD using Hanifin and Rajka criteria (HRC). Results: The prevalence of AD was found to be 8.12%. Age of presentation ranged from 4 months to 16 years of age, with a mean age of 4.18 ± 3.88 years. 42% of patients had personal and 52.50% of patients had a family history of atopy. We report pruritus as a major presenting symptom seen in 100% of children with AD. Typical morphology and distribution were observed in 97.50% of cases, with the face being the most commonly affected site in infants (95.08%) and flexural involvement more common in children (77.70%). Infants had acute eczema (63.93%) and children with AD mostly presented with chronic eczematous lesions (58.27%). The most common minor feature of HRC observed was xerosis, seen in 94% of patients. Amongst atypical features, scalp scaling was the most common feature seen in 17%. SCORAD Index grading was mild in 49.50% of children with AD, moderate in 40.50% and severe grading was seen only in 10% of children. Conclusion: Clinical features, prevalence and severity of AD are affected by various geographical, environmental and local factors such as lifestyle, clothing and eating/dietary factors.

A deep learning based model for diabetic retinopathy grading

Diabetic retinopathy stands as a leading cause of blindness among people. Manual examination of DR images is labor-intensive and prone to error. Existing methods to detect this disease often rely on handcrafted features which limit the adaptability and classification accuracy. Thus, the aim of this research is to develop an automated and efficient system for early detection and accurate grading of diabetic retinopathy severity with less time consumption. In our research, we have developed a deep neural network named RSG-Net (Retinopathy Severity Grading) to classify DR into 4 stages (multi-class classification) and 2 stages (binary classification). The dataset utilized in this study is Messidor-1. In preprocessing, we have used Histogram Equalization to improve image contrast and denoising techniques to remove noise and artifacts which enhanced the clarity of the fundus images. We applied data augmentation techniques to our preprocessed images in order to tackle class imbalance issues. Augmentation techniques involve flipping, rotation, zooming and adjustment of color, contrast and brightness. The proposed RSG-Net model contains convolutional layers to perform automatic feature extraction from the input images and batch normalization layers to improve training speed and performance. The model also contains max pooling, drop out and fully connected layers. Our proposed RSG-Net model achieved a testing accuracy of 99.36%, specificity of 99.79% and a sensitivity of 99.41% in classifying diabetic retinopathy into 4 grades and it achieved 99.37% accuracy, 100% sensitivity and 98.62% specificity in classifying DR into 2 grades. The performance of RSG-Net is also compared with other state-of-the-art methodologies where it outperformed these methods.

P-2178. Can serum ferritin be used as a marker of severity in dengue fever?: a prospective observational study from North India

Abstract Background Dengue has a variable clinical course and there is no standardised marker for predicting dengue severity. Studies have shown higher ferritin levels in dengue compared to other febrile illnesses. Prospective studies to show correlation of ferritin with dengue severity are lacking. Demographic profile and workflow From 134 patients 99 were selected for the study , 35 were excluded as per the exclusion criteria (figure 1 flowchart). Majority of the patients were young (figure 3) with male predominance (figure 2), the male female percentages and age did not vary significantly across different grades of severity (table1 and figure 4). Methods Single centre prospective observational study conducted over 2 years. Patients of chronic inflammatory diseases, thalassemia, haematological malignancy or severe anemia (Hb < 7gm/dl) were excluded. Two ferritin samples 3 days apart measured by automated BECKMAN COULTER DxI.800 immunoassay analyzer. Clinical features and median ferritin value across different dengue severties In Figure 5 the pie chart shows that majority of the patients were dengue without warning signs , approximately 1/5th were severe dengue. Figure 6 shows that initial clinical features were more or less similar in the three groups of severities , however bleeding, pain abdomen , vomiting were more common in severe dengue group. Table 2 showing median ferritin values of day 0 and day 3 ferritin in different severity groups and whether their differences are statistically significant between each groups or not. The Box and whisker plots in figure 7, 8 and 9 shows the same with corresponding p values and Median ferritin level annotated. Results Total study population was 99 patients with median age of 28 years (24.5-34.5) and male predominance (68%). 2009 WHO classification wise 43% were dengue without warning signs 36% dengue with warning signs and 21% were severe dengue patients. Both day 0 and day 3 ferritin median value were higher across all three groups and the difference were statistically significant (p=0.00002 and p=0.045 respectively). Day 0 ferritin median value difference was statistically significant between severe dengue and dengue without warning sign (0.00001) and warning sign group (p=0.0003). In case of early ferritin sample (within day 7 of illness) it was significantly different between all groups. Serum ferritin also showed strong positive correlation with AST, ALT and negative correlation with Albumin levels. ROC curve analysis showed that a ferritin cut off of 9185 ng/ml with AUC 0.811, standard error 0.06 and 95% CI of 0.69-0.92 could differentiate severe from non severe dengue with 52.4% sensitivity and 97.4% specificity. For early ferritin sample cut off becomes 2132 ng/ml with a 70% sensitivity and 82.4% specificity with AUC 0.821, standard error 0.085 and 95% CI of 0.65-0.98. Multivariate logistic regression shows baseline platelet counts < 50000 cells/uL [OR 4.7, p=0.02, 95% CI 1.19-18.54] and Albumin < 3.5 gm/dL [OR 6.33 p=0.007 95% CI 1.67-24.06] to be independent predictors of severe dengue. Day 0 ferritin level > 9185ng/mL gave an Odd’s ratio of 10.47 with p=0.052 and 95% CI [0.98-112]. Correlation of ferritin with various biochemical parameters and Ferritin cutoff value to differentiate Severe from Non severe dengue by ROC curve Table 3 and Figure 10 Scatter plot showing strong positive correlation between serum ferritin and SGOT/ SGPT levels, and negative correlation with serum albumin level .Figure 11 ROC curve analysis showing the ferritin cutoff being 9185ng/ml to differentiate between severe and non severe dengue. If sample taken within day 7 of illness the cut off becomes 2132 ng/ml (Figure 12) Conclusion Ferritin can be a useful biomarker for differentiating different grades of dengue severity especially if sample taken in the 1st week of illness. Serum ferritin cut off values can be used to predict severe dengue. Multivariate Logistic regression to find independant predictor of severe Dengue Table 4 showing Multivariate logistic regression result, which reveals baseline platelet count <50000 and Albumin level <3.5gm/dL to be independent predictor of severe dengue.Day 0 Ferritin cutoff of 9185 ng/dL as per the ROC curve analysis shows that the Odds of prediction of severe dengue is 10.47 (p=0.052 and 95% CI 0.98-112). Disclosures All Authors: No reported disclosures

Prognostic significance of tricuspid regurgitation grading using different echocardiographic approaches

Abstract Introduction Tricuspid regurgitation (TR) is routinely graded using quantitative and qualitative echocardiographic parameters. The current grading scheme consists of five TR grades and primarily incorporates vena contracta (VC) and effective regurgitation orifice area (EROA) assessed by the proximal isovelocity surface area (PISA) method. Additionally, an angle-corrected PISA method was proposed as the standard approach seem to underestimate especially ventricular TR. Purpose Since different measurements may lead to different TR severity grades, the present study aimed to evaluate the prognostic significance of TR grading using various approaches. Methods Hospitalized patients with heart failure (HF) according to current guidelines of the European Society of Cardiology (ESC) were enrolled from 2020 to 2022 (NCT04570098). Inclusion criteria comprised an echocardiographic examination up to three months prior to study participation. TR was graded into the categories moderate to torrential according to the recommended standard, including all quantitative and qualitative parameters as proposed by the guidelines, biplane VC, PISA EROA, and angle-corrected PISA EROA. Survival status was assessed during twelve-month follow-up. Cox regression analysis and log-rank test were used to evaluate the prognostic value of TR grades according to the different echocardiographic methods with the reference category none or mild TR. Results A total of 1003 HF patients were enrolled, including 66% with none or mild TR. The prevalence of moderate to torrential TR depending on the use of the different methods was as follows: 18% moderate, 10% severe, 2% massive, and 3% torrential TR according to quantitative and qualitative parameters; 12% moderate TR, 6% severe TR, 4% massive TR, and 4% torrential TR assessed by PISA EROA; 9% moderate TR, 6% severe TR, 3% massive TR, and 6% torrential TR according to angel-corrected PISA EROA; as well as 13% moderate TR, 14% severe TR, 4% massive TR, and 1% torrential TR measured by VC. During the study period, the overall-mortality rate reached 15%. A more severe TR was associated with an increase in mortality regardless of the TR grading approach (log-rank test p<0.001). As shown in Table 1, only TR grading based on VC consistently demonstrated an increased mortality risk across all severity grades. Conclusion There are various parameters for TR quantification used in clinical routine. Overall, a more severe TR was associated with an increase in all-cause mortality in HF patients. VC may be superior to PISA EROA and angle-corrected PISA EROA to differentiate the mortality risk of moderate to torrential TR.

Clinical value of preoperative cardiac magnetic resonance imaging and echocardiography to identify post-operative left ventricular dysfunction in primary mitral regurgitation

Abstract Background Post-operative left ventricular (LV) dysfunction remains a common adverse consequence in patients with primary mitral regurgitation (MR) undergoing mitral valve (MV) surgery. Currently, cardiac magnetic resonance imaging (CMR) is a very useful imaging modality that complements echocardiography (Echo) in providing accurate grading of MR severity in these patients. Yet it remains unclear whether the consideration of CMR-assessed LV volumes and function would offer advantages over conventional echocardiographic LV measurements in identifying patients at risk of LV systolic dysfunction after MV surgery. Purpose We sought to compare the relationship between CMR- or Echo-assessed preoperative LV volumetric and function measurements and the occurrence of post-operative LV systolic dysfunction in patients with chronic significant primary MR undergoing MV surgery. Methods The study population consisted of 214 patients (median age: 59 years, 20% women) with chronic significant primary MR due to MV prolapse or flail who underwent echocardiography and CMR in 2 tertiary centers, between 2005 and 2022, before MV repair surgery. The endpoint was the occurrence of post-operative LV systolic dysfunction (defined as LV ejection fraction [EF] < 50%) at echocardiographic follow-up when available. ROC curves were used to evaluate relations between preoperative Echo or CMR characteristics and post-operative LV dysfunction. Side-by-side comparisons of AUCs were done using DeLong’s tests. Results At echocardiographic follow-up, 40 patients (19%) had post-operative LV dysfunction, with a median follow-up time of 8.6 months (interquartile range: 6.7 – 12.5 months) after MV surgery. Compared with those with normal LV function, patients with post-operative LV dysfunction exhibited higher absolute and indexed (ind) LV end-systolic diameters (ESD) and volumes (ESV) (all p<0.043, Figure 1). These patients also showed lower preoperative CMR-assessed LVEF (p=0.004), while Echo-LVEF did not show a significant relationship (p=0.071). Additionally, no relationship was found between MR quantitative parameters (regurgitant orifice area, volume, or fraction) and post-operative LV function (all p>0.247). The AUCs of the imaging preoperative characteristics tested (LVESD, indLVESD, Echo-indLVESV, CMR-indLVESV, Echo-LVEF, CMR-LVEF) numerically ranged from 0.59 (0.50-0.69), p=0.034 (Echo-LVEF) to 0.69 (0.60-0.77), p<0.001 (Echo-indLVESD, Figure 2). No significant differences were found in the side-by-side comparisons of the AUCs (all p>0.118). Conclusion In this series of patients with chronic significant primary MR who underwent MV surgery, conventional preoperative Echo and CMR LV measurements had similar diagnostic value in detecting post-operative LV systolic dysfunction. Our results indicate that both echocardiography and CMR are valuable imaging tools for identifying primary MR patients at risk of post-operative LV dysfunction. Figure 1 Figure 2

Echocardiographic predictors of left ventricular interstitial fibrosis in chronic primary mitral regurgitation with preserved ejection fraction: the underrecognized role of diastolic dysfunction

Abstract Background Myocardial fibrosis is a well-known risk factor for morbidity and mortality in patients with chronic primary mitral regurgitation (MR). Extracellular volume (ECV), a marker of interstitial fibrosis assessed with cardiovascular magnetic resonance imaging (CMR), was correlated with echocardiographic markers of left ventricular (LV) systolic and diastolic dysfunction in a previous study cohort of patients with severe primary MR. In addition, diastolic dysfunction has recently been recognized as a distinct phenotype in patients with primary MR associated with similar prognosis compared to patients with systolic dysfunction. Purpose To investigate whether echocardiographic parameters of subclinical LV systolic function, diastolic dysfunction or MR severity are correlated with interstitial fibrosis in chronic primary MR patients with a preserved ejection fraction (EF). Methods Prospective inclusion of patients with chronic primary MR and a LVEF>50%. All patients underwent transthoracic echocardiography and CMR scan (1.5T). Echocardiographic assessment of LV systolic and diastolic function was performed, including global longitudinal strain (GLS). MR severity was assessed using a multi-integrative approach. Extracellular volume (ECV) was calculated from the native and post-contrast T1 times. Results A total of 50 patients with primary MR were included (58% males, age 56 ± 16 years old). CMR and transthoracic echocardiography were performed within 30 ± 65 days. MR severity was variable with 20% mild, 32% moderate, 12% moderate-severe and 36% severe MR. Mean LVEF and GLS were within normal range (59.1% ± 5.3% and –19.8% ± 2.9% respectively). Mean ECV was 27.8% ± 2.5%. ECV did not show a significant correlation with MR severity grade or markers of LV systolic function like LVEF (Rho=-0.121, p=0.42) or GLS (Rho=0.089, p=0.59). However, we did observe a statistically significant correlation between ECV and markers of LV diastolic dysfunction such as mean E/e’ (Rho=0.291, p=0.050) and deceleration time (Rho=-0.308, p=0.037). Even in patients with non-severe MR (grade 1 to 3), the correlation between ECV and E/e’ remained significant (Rho=0.438, p=0.017). In a multivariate regression analysis E/e’ and MR grade were associated with ECV, even after correction for age and gender (R squared 0.248, p=0.017 and p=0.044 respectively). Conclusion In patients with chronic primary MR and a preserved LVEF, the presence of interstitial fibrosis, measured as ECV, was associated with echocardiographic parameters of diastolic rather than systolic dysfunction, independent of MR severity. These findings suggest that diastolic dysfunction can be a subclinical marker of myocardial fibrosis (and subsequently adverse outcomes) in patients with primary MR. Correlation ECV and E/e'

Aortic valve repair in adults: long-term clinical outcomes and echocardiographic evolution in different valve repair techniques.

Aortic valve repair/sparing have been established as effective treatments for aortic regurgitation and/or aortic aneurysms. However, concerns remain regarding long-term durability, reproducibility, and patient selection. This study aims to asses long-term clinical and echocardiographic outcomes, with a focus on aortic regurgitation grade and left ventricular ejection fraction evolution, in adults undergoing these procedures. Adult patients in the Heart Valve Society Aortic Valve Database, undergoing any aortic valve repair/sparing technique were included. Time-to-event analyses were used for clinical outcomes and mixed-effects-models for left ventricular ejection fraction and aortic regurgitation evolution. Techniques: isolated valve repair (GROUP-1), ascending aortic replacement +valve repair (GROUP-2), partial-root replacement +/-valve repair (GROUP-3), and valve-sparing root replacement +/-valve repair (GROUP-4). Survival at 10-years was comparable to the general population in each group. The 10-year cumulative incidence of reintervention was 19.5%(95%CI:16.70-22.40%) in GROUP-1 [Including only double external annuloplasty in GROUP-1, reintervention was not significantly different between techniques (p = 0.112)], 13.8% (95%CI: 10.10-18.10%) in GROUP-2, 12.7%(95%CI:5.50-22.90%) in GROUP-3, and 8.5%(95%CI:7.00-10.10%) in GROUP-4 (p < 0.001). Severe preoperative aortic regurgitation grade [HR: 1.95(95%CI:1.19-3.21),p<0.001] and left ventricular end-diastolic diameter [HR:1.03(95%CI:1.00-1.05),p<0.001] were predictive of reintervention in GROUP-4, patch use was a predictor in all groups. Predicted left ventricular ejection fraction (%) initially increased(p < 0.001) and then stabilized. This study found that aortic valve repair/sparing techniques provide a viable and effective treatment option that should be considered for all eligible patients with aortic regurgitation and/or aortic root/ascending aortic aneurysms, given their potential to restore life expectancy and provide good hemodynamic outcomes with an acceptable hazard of reintervention.

The Correlation Between Meibomian Gland Dysfunction and Aniridia-Associated Keratopathy: A Prospective Analysis

Background/Objectives: Aniridia is a rare congenital disorder characterized by structural and functional abnormalities in ocular development due to PAX6 haploinsufficiency, leading to complications such as aniridia-associated keratopathy (AAK). Meibomian gland dysfunction (MGD), a prevalent yet underexplored condition in aniridia, exacerbates tear film instability and chronic ocular surface inflammation, contributing to AAK progression. This study investigates the relationship between MGD severity and AAK in individuals with aniridia. Methods: This prospective randomized study included 113 participants (53 with aniridia and 60 controls). Comprehensive ophthalmic evaluations, including noninvasive meibography, were performed. The MGD severity was assessed using a standardized meiboscore scale, while the AAK severity was classified according to established clinical grading criteria. Statistical analyses, including Spearman’s correlation and chi-squared tests, were used to evaluate the relationships among MGD, AAK, and visual acuity. Results: MGD was significantly more prevalent and severe in the aniridia group compared to controls (p &lt; 0.00001). A strong positive correlation was observed between MGD severity and AAK grade (r = 0.72, p &lt; 0.00001), with both conditions associated with reduced best-corrected visual acuity (BCVA; r = −0.80 and −0.86, respectively, p &lt; 0.0001). Age was positively correlated with MGD (r = 0.47, p = 0.0004) and AAK (r = 0.34, p = 0.0123), with gender-specific trends observed in females. Conclusions: MGD significantly contributes to AAK progression and visual impairment in aniridia. Meibography offers valuable insights into MGD severity, supporting early diagnosis and targeted interventions. Addressing MGD through tailored therapies could mitigate AAK progression and improve visual outcomes in this challenging condition.

Identification of serum tRNA-derived small RNAs biosignature for diagnosis of tuberculosis

ABSTRACT The tRNA-derived small RNAs (tsRNAs) are a new class of non coding RNAs, which are stable in body fluids and can be used as potential biomarkers for disease diagnosis. However, the exact value of tsRNAs in the diagnosis of tuberculosis (TB) is still unclear. The objective of the present study was to evaluate the performance of the serum tsRNAs biosignature to distinguish between active TB, healthy controls, latent TB infection, and other respiratory diseases. The differential expression profiles of tsRNAs in serum from active TB patients and healthy controls were analyzed by high-throughput sequencing. A total of 905 subjects were prospectively recruited for our study from three different cohorts. Levels of tsRNA-Gly-CCC-2, tsRNA-Gly-GCC-1, and tsRNA-Lys-CTT-2-M2 were significantly elevated in the serum of TB patients compared to non-TB individuals, showing a correlation with lung injury severity and acid-fast bacilli grades in TB patients. The accuracy of the three-tsRNA biosignature for TB diagnosis was evaluated in the training (n = 289), test (n = 124), and prediction (n = 292) groups. By utilizing cross-validation with a random forest algorithm approach, the training cohort achieved a sensitivity of 100% and specificity of 100%. The test cohort exhibited a sensitivity of 75.8% and a specificity of 91.2%. Within the prediction group, the sensitivity and specificity were 73.1% and 92.5%, respectively. The three-tsRNA biosignature generally decreased within 3 months of treatment and then remained stable. In conclusion, the three-tsRNA biosignature might serve as biomarker to diagnose TB and to monitor the effectiveness of treatment in a high-burden TB clinical setting.

The Cluster Headache Impact Questionnaire : Measuring headache-related impairment in cluster headache patients

Cluster headache is asevere primary headache disorder, which can be associated with asubstantial impairment for sufferers. The Cluster Headache Impact Questionnaire (CHIQ) is ashort questionnaire for measuring the cluster headache-specific impairment. A5-stage severity grading from "no to low impairment" to "'extreme impairment" was established based on the results of an English-speaking patient collective. The present article tested whether the severity classification can be transferred to aGerman patient group. Data from 196 patients with episodic and chronic cluster headache were examined during an active episode. The severity grading classification of the CHIQ also showed clinically relevant results in the German collective, i.e., the five degrees of severity showed significant differences with respect to attack frequency, intake of acute medication and unspecific headache-related impairment (HIT-6) and quality of life (SF-12v2). Interestingly, 32out of 52patients with episodic cluster headache outside the active epísode suffered an impairment above the lowest severity grade, i.e., at least a moderate impairment. In conclusion, the CHIQ provides ashort instrument to document the current impairment in cluster headache patients. The severity grading classification presented here facilitates the clinical interpretation.

P0298 Revolutionizing Diagnostics: Evaluating ChatGPT-4’s Performance in Ulcerative Colitis Endoscopic Assessment

Abstract Background The Mayo Endoscopic Subscore (MES) is a widely utilized measure for assessing endoscopic disease activity in ulcerative colitis (UC). This assessment has a key role in clinical practice as endoscopic remission is a long-term therapeutic objective. Artificial intelligence has emerged as a promising tool for enhancing diagnostic precision and addressing inter-observer variability among endoscopists. This study aims to evaluate the diagnostic accuracy of ChatGPT-4, a multimodal large language model (LLM), in identifying and grading endoscopic images of UC patients using the MES as a reference standard, without prior configuration or fine-tuning. Methods Real-world endoscopic images of UC patients were obtained for severity assessment and reviewed by an expert consensus board. Each image was classified by severity grade (0-3) based on the MES. Only images that were uniformly graded by the consensus board were subsequently provided to three IBD specialists and ChatGPT-4 in three separate sessions. Severity gradings of the IBD specialists and ChatGPT-4 were compared with assessments made by the expert consensus board. Results Fifty endoscopic images were initially evaluated by the expert consensus board. Of those, 30 images (60%) were graded with complete agreement of MES among the experts. Compared to the consensus board, ChatGPT4’s MES gradings were accurate in 26/30 (86.7%), 21/30 (70%) and 24/30 (80%) with a mean accuracy rate of 78.9%. The IBD specialists gradings were accurate in 24/30 (80%), 24/30 (80%) and 25/30 (83.3%) with a mean accuracy rate of 81.1% (figure 1). There was no statistically significant difference in mean accuracy rates between the two groups (p = 0.71). Conclusion ChatGPT-4 has the potential of assessing mucosal inflammation severity from endoscopic images of UC patients, without prior configuration or fine-tuning. Performance rates were comparable to IBD specialists. Further research and validation are warranted to explore the broader applications of LLMs and their integration into diagnostic workflows.

Prognostic analysis of helical tomotherapy stereotactic body radiotherapy in multiple primary or second primary lung cancers

PurposeTo evaluate the safety and efficacy of Helical Tomotherapy stereotactic body radiotherapy (HT-SBRT) in treating multiple primary lung cancers (MPLCs) and second primary lung cancer (SPLC).MethodsFrom January 2010 to September 2023, 106 MPLCs and SPLC (T1-3N0M0) underwent HT-SBRT. The cumulative incidence for local recurrence (LR) was calculated using the competing risk approach and compared using Gray’s test. Cancer-specific survival (CSS) and progression-free survival (PFS) were assessed using Kaplan-Meier analysis and log-rank tests.ResultsAfter adjusting for competing risks, the LR rates for all lesions (n = 150) was 15.3%, with 2- and 4-year rates of 7.5% and 11.4%. For second primary lung nodules post-surgery, the cumulative incidence of LR was 16.1%, with 2- and 4-year rates of 6.9% and 8.7%. In MPLCs treated with HT-SBRT, the cumulative incidence of LR was 14.3%, with 2- and 4-year rates of 8.2% and 14.3%. In patients with MPLCs treated with HT-SBRT (n = 27), the CSS rates at 2, 4, and 10 years were 90.5%, 78.6%, and 53.6%, respectively, and the PFS rates were 59.5%, 32.8%, and 24.6%. In patients with SPLC who received HT-SBRT after surgery (n = 79), the CSS rates at 2, 4, and 10 years were 90.9%, 81.7%, and 61.0%, respectively, while the PFS rates were 75.4%, 64.4%, and 58.5%. Additionally, 0.9% of patients experienced grade 3 acute radiation pneumonitis, and no severe (grade 4–5) toxicities were reported.ConclusionsHT-SBRT may be a safe and effective treatment for MPLCs and SPLC, though prospective studies are needed to confirm its efficacy.

DOP077 EndoUC: an AI-assisted endoscopic Ulcerative Colitis activity grading application for deployment in clinical trials

Abstract Background Manual scoring of ulcerative colitis (UC) disease activity from endoscopy videos using the Modified Mayo Score (mMS) by experts is known to have high inter-rater and intra-rater variability.1 In clinical trials, central reviewers review endoscopy videos and provide a single score for the entire video leading to a loss of transparency with no evidence of scoring rationale or segmental involvement. We developed an AI-assisted severity scoring application for clinical trials to address this challenge by intelligently highlighting video segments showing pathological information and providing a continuous scoring approach to severity grading. Methods Unlike previous approaches that rely heavily on large-scale, expensive, and restrictive frame-level expert labels, we developed our models on video-level grading available in typical clinical trial settings. We used data from the brazikumab clinical trial [NCT03616821], comprising 423 videos from 249 patients scored on the mMS scale. Our preprocessing module removes uninformative, low-quality frames and applies detection, tracking and alignment algorithms to identify regions of interest across frames. Our EndoUC model has 3 components: a pathology-enriched frame identification module (PEFIM), an aggregator, and a classifier.The PEFIM module identifies regions that characterise signs of UC, such as ulcers or erosions. The aggregator and classifier modules learn to combine the information at the video level. We focus on the clinical utility of the EndoUC model in two ways: (i) having task-specific classifiers focusing on clinical decision boundaries of UC and (ii) enhancing scoring granularity of UC severity prediction using ordinal regression. Results We developed an application to enable experts to review lengthy endoscopy footage in clinical trials efficiently. The app allows seamless navigation to key regions identified by the EndoUC and transparently reveals the basis of the AI model’s assessments. We conducted 5-fold cross-validation on the clinical trial data and evaluated the model on a held-out test set with 87 videos. The remission (mMS 0, 1 vs 2, 3) model performs with an AUC-ROC of 0.85, F1 of 0.87, normal/inactive and severe models with AUC-ROC of 0.81and 0.83 respectively. The continuous grading model has an MSE of 0.42 and MAE of 0.40. Conclusion We developed an AI-assisted reading tool for UC endoscopic severity assessment to help accelerate clinical trails through rapid evaluation of patient eligibility, detection of treatment response grounded by key region evidence, and potential for continuous grading of endoscopic changes.

Prediction model for severe vesicoureteral reflux in children with urinary tract infection and/or hydronephrosis.

As voiding cystourethrography is invasive and exposes to radiation and urinary tract infection (UTI), identifying only high-grade reflux is important. We aimed to identify clinical, laboratory and imaging variables associated with high-grade primary reflux in children presenting with UTIs and/or urinary tract dilatation and develop a prediction model for severe reflux. Data of children who underwent voiding cystourethrography due to UTI and/or urinary tract dilatation were retrospectively analyzed for demographic, clinical and imaging findings. Patients with severe (grades 4-5) reflux were compared with the rest for these parameters and a prediction model was developed for severe reflux. The study included 1044 patients (574 female). Severe reflux was present in 86 (8.2%) patients. Age < 2years, male sex, non-E. coli uropathogens, UTD-P3 dilatation and multiple kidney scars on DMSA scintigraphy were associated with severe reflux. Using these variables a prediction model for severe reflux with a score ranging from 0-7 and accuracy rate of 93.4% was developed. A score ≥ 5 had sensitivity 44.2%, specificity 97.4%, PPV 60.3%, NPV 95.1% and OR 29.5 for severe reflux. Scores ≥ 5 and ≥ 4 catch 44% and 73% of severe reflux, while prevent invasive voiding cystourethrography in 94.0% and 83.6% of patients, respectively. Age < 2years, male sex, non-E. coli uropathogen growth, presence of UTD-P3 dilatation on ultrasonography and multiple scars on DMSA scintigraphy are risk factors for severe reflux. A scoring system based on these variables appears to be effective in predicting the presence of severe reflux and eliminating unnecessary voiding cystourethrography.

Co-delivery of IL-1Ra and SOX9 via AAV inhibits inflammation and promotes cartilage repair in surgically induced osteoarthritis animal models.

Osteoarthritis (OA), a prevalent joint disorder, can lead to disability, with no effective treatment available. Interleukin-1 (IL-1) plays a crucial role in the progression of OA, and its receptor antagonist (IL-1Ra), a natural IL-1 inhibitor, represents a promising therapeutic target by obstructing the IL-1 signaling pathway. This study delivered IL-1Ra via adeno-associated virus (AAV), a gene therapy vector enabling long-term protein expression, to treat knee osteoarthritis (KOA) in animal models. scAAV-oIL-1Ra-I1/2 injected directly into the joint in both MMT/ACLT-induced KOA model rat improved abnormal gait (increasing footprint area and pressure), subchondral bone lesions, and significantly reduced cartilage wear and pathological scores. In the MMT-induced KOA rabbit model, weight-bearing asymmetry (indicating pain) improved after 8 weeks of scAAV-oIL-1Ra-I1/2 administration, and X-ray showed decreased K-L scores (severity grade), reduced cartilage loss, and lower pathology scores compared to untreated animals. Additionally, sex-determining region Y-type high mobility group box 9 (SOX9) was co-delivered with IL-1Ra via AAV in ACLT + MMT-induced KOA rats. The combined treatment significantly alleviated subchondral bone lesions, cartilage destruction, synovial inflammation, and pathological scores, demonstrating superior efficacy compared to either treatment administered alone. Co-delivering IL-1Ra and SOX9 inhibited IL-1 mediated inflammatory signaling, maintained cartilage homeostasis, and promoted its repair in KOA models, suggesting potential for clinical use.