Younger Patient Age Research Articles

Abstract TMP88: Clinical Utility of Genetic Testing in Pediatric and Young Adult Hemorrhagic Stroke and Cerebrovascular Malformations

Introduction: Pediatric and young adult cerebrovascular disease is more commonly associated with genetic conditions compared to in adults. This pilot study aims to characterize utility of genetic testing in a pediatric and young adult neurovascular clinic. Methods: This was a single center cohort study of pediatric and young adult patients (age <25 years) with cerebrovascular conditions who underwent clinical genetic testing between 7/2023-7/2024. Cerebrovascular conditions included brain or spine AVM, cavernous malformation, cerebral aneurysm, Moya-Moya vasculopathy, and/or unexplained hemorrhagic stroke. Individuals with perinatal or isolated arterial ischemic stroke were not included. Genetic testing ranged from a custom gene panel (including 4-175 genes) to whole exome/genome sequencing. Chart review was performed by a pediatric vascular neurologist to determine clinical details and genetic results. Identified genetic variants were further classified as 1) pathogenic or highly suspicious, 2) actionable but unrelated to phenotype, and 3) possibly relevant. Results: Twenty patients underwent genetic testing, including 7 with brain or spine AVM, 3 with ruptured cerebral aneurysm, 5 with spontaneous intracranial hemorrhage without underlying vascular malformation, and 5 with other cerebrovascular malformations. Median age at testing was 14 years (range 2mo – 24 years), and 11 (55%) were male. Panel testing was performed on 16/20; exome/genome trio sequencing was performed in 4/20. Definite pathogenic or highly suspicious variants relevant to underlying phenotype were noted in 4/20 (20%), an unrelated but actionable pathogenic variant was noted in 1/20 (5%), and possibly relevant variants were noted in an additional 3/20 (15%) patients. Genes with identified variants included RNF213 (n=2), ENG, EPHB4, F2, F5, COL4A1, and DIAPH1. Positive or negative results informed or changed clinical management in 17/20 (85%) patients, prompting additional testing, altered imaging surveillance, and/or expectant guidance for the patient and family members. Conclusions: Genetic testing has become increasingly available and has relatively high yield in pediatric and young adult hemorrhagic stroke and cerebrovascular malformations. Panel or exome/genome-based testing can inform care in these individuals and their families. Larger cohort studies are needed to determine more precise yield of genetic testing across a variety of cerebrovascular conditions.

P-1920. The influence of comorbidity, age, sex, and immunosuppression on COVID-19 mortality throughout the course of the SARS-CoV-2 pandemic in Europe: Data from the LEOSS study

Abstract Background Population immunity against SARS-CoV-2 has increased, resulting in a decline of COVID-19 mortality. The aim of the study was to analyse the COVID-19-related mortality over the pandemic, stratified by a model of groups at risk of severe COVID-19. Predicted probability of COVID-19-related death in dependence of age and SARS-CoV-2 variant. Methods COVID-19-related patients were included from January 2020 to November 2022 using the international multicentric cohort study Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS). Predicted probability of COVID-19-related death was calculated using a multivariate logistic regression model adjusted to age, gender and vaccination status.Figure 2:Predicted probability of COVID-19-related death in dependence of gender and SARS-CoV-2 variant. Results In total, 12,096 patients were included. The overall mortality was 13% (n=1546), decreasing from 14% during the wildtype (wt) period (01/2020-12/2020), to 13%, 10%, and 6% in the alpha (α) (01/2021-06/2021), delta (δ) (07/2021-12/2021), and omicron (Ω) (01/2022-11/2022) periods, respectively. Patients aged 66-75, 76-85, and >85 years (y) had a 13.3-, 22.5-, and 40.4-fold higher odds of mortality compared to 26-35y old patients (p< 0.001 in all listed comparisons). This increase in mortality between younger (age: 26-35y, mortality: wt 2%, Ω 1%) and older patients (age: >85y, mortality: wt 41%, Ω 23%) decreased with the shift from wt (increase of 39 percentage points) to Ω (increase of 22 percentage points) (Fig. 1). The overall mortality in males (m) (15%) was higher than in females (f) (10%), but this gender-specific difference leveled off with the shift from wt (m: 19%, f: 10%) to Ω (m: 9%, f: 9%) (Fig. 2). Referring to the difference in mortality between patients with zero and four comorbidities, the predicted increase in mortality during the periods wt, α, δ, and Ω was 14, 14, 1, and 0 percentage points, respectively (Fig. 3). Concerning severely immunosuppressed patients, mortality significantly decreased throughout the pandemic (wt: 15%, Ω: 4%, p=0.031) (Fig. 4).Figure 3:Predicted probability of COVID-19-related death in dependence of number of comorbidities and SARS-CoV-2 variant.Comorbidities include cardiovascular diseases, renal diseases, diabetes, pulmonary diseases, liver diseases, rheumatic diseases, haemato-oncological diseases, neurological diseases, autoimmune diseases and HIV/AIDS. Conclusion Overall mortality decreased during the pandemic. This change was observed even among severely immunosuppressed patients. Age, gender, and the number of comorbidities were identified as relevant mortality risk factors, with decreasing importance as the pandemic progressed.Figure 4:Subgroup analysis for severely immunosuppressed patients.Severely immunosuppressed group, including: stem cell transplant, organ transplant, b-cell depletion, autoimmune disease, immunosuppressive therapy (corticosteroids, methotrexate, azathioprine, ciclosporin, calcineurin-inhibitors, mTOR-inhibitors). Disclosures Jochen Schneider, n/a, AbbVie: Grant/Research Support|AbbVie: Honoraria|AbbVie: non-financial support|Central Innovation Program for small and medium-sized enterprises: Grant/Research Support|Central Innovation Program for small and medium-sized enterprises: Honoraria|Central Innovation Program for small and medium-sized enterprises: Central Innovation Program for small and medium-sized enterprises|Deutsche Forschungsgemeinschaft: Grant/Research Support|Deutsche Forschungsgemeinschaft: Honoraria|Deutsche Forschungsgemeinschaft: non-financial support|Diasorin: Grant/Research Support|Diasorin: Honoraria|Diasorin: non-financial support|Dr. Falk Pharma GmbH: Grant/Research Support|Dr. Falk Pharma GmbH: Honoraria|Dr. Falk Pharma GmbH: non-financial support|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Gilead Sciences: non-financial support|GSK/ViiV Healthcare: Grant/Research Support|GSK/ViiV Healthcare: Honoraria|GSK/ViiV Healthcare: non-financial support|Janssen-Cilag: Grant/Research Support|Janssen-Cilag: Honoraria|Janssen-Cilag: non-financial support|MSD: Grant/Research Support|MSD: Honoraria|MSD: non-financial support|Takeda Pharmaceutical: Grant/Research Support|Takeda Pharmaceutical: Honoraria|Takeda Pharmaceutical: non-financial support Christoph Spinner, MD, AbbVie: Honoraria|Apeiron: Honoraria|AstraZeneca: Grant/Research Support|AstraZeneca: Honoraria|BBraun Melsungen: Honoraria|BBraun Melsungen: non-financial support|BioNTech: Honoraria|Cepheid: Grant/Research Support|Eli Lilly: Honoraria|Formycon: Honoraria|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Gilead Sciences: non-financial support|GSK: Honoraria|Janssen-Cilag: Grant/Research Support|Janssen-Cilag: Honoraria|Molecular partners: Honoraria|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Honoraria|Roche: Honoraria|Shionogi: Honoraria|SOBI: Honoraria|Synairgen: Honoraria|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: Honoraria Maria JGT Vehreschild, Prof. Dr. med., 3M: Honoraria|Ärztekammer Niedersachsen: Honoraria|ADKA: Honoraria|Akademie für Infektionsmedizin: Honoraria|Astellas: Honoraria|Berliner Dialy Seminar: Honoraria|Biontech: Grant/Research Support|CED Service: Honoraria|DiaLog Service: Honoraria|EUMEDICA: Advisor/Consultant|EUMEDICA: Honoraria|Falk Foundation: Honoraria|Ferring: Honoraria|Forum für medizinische Fortbildung Gmbh: Honoraria|GILEAD: Honoraria|Heel: Grant/Research Support|Helios Kliniken: Honoraria|Institute Merieux: Honoraria|Janssen: Honoraria|Kit Kongress: Honoraria|Klinikum Essen: Honoraria|Klinikum Leverkusen: Honoraria|Lahn-Dill-Kliniken: Honoraria|Landesärztekammer Hessen: Honoraria|Limbach Gruppe SE: Honoraria|MaaT: Advisor/Consultant|MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Honoraria|Roche: Advisor/Consultant|Roche: Grant/Research Support|SD Biosensor: Grant/Research Support|St. Johannes Hospital: Honoraria|St. Josef Hospital: Honoraria|SUMIT OXFORD Ltd.: Honoraria|Tillotts: Advisor/Consultant|Tillotts: Honoraria|Uniklinik Frankfurt: Honoraria|Uniklinik Köln: Honoraria|Uniklinik Karlsruhe: Honoraria|Universitätsklinikum Freiburg: Honoraria|Universitätsklinikum Heidelberg: Honoraria Floran Voit, MD, Gilead Sciences: Honoraria|Gilead Sciences: non-financial support|MSD: Grant/Research Support|Pfizer: non-financial support|ViiV Healthcare: non-financial support Johanna Erber, Dr. med., Gilead Sciences: non-financial support|Pfizer: non-financial support|Tillotts Pharma AG: non-financial support|ViiV Healthcare: non-financial support

An investigation into the frequency of negative appendectomies and contributing factors in patients with suspected acute appendicitis

Background: Acute appendicitis is a common cause of acute abdominal pain in young adults, with varying diagnosis accuracy leading to a significant rate of negative appendectomies, particularly in females and younger patients. This study aimed to evaluate the prevalence of negative appendectomy in patients with suspected acute appendicitis. Methods: A cross-sectional study was conducted at Dhaka medical college hospital from January 2022 to June 2024, involving 220 patients diagnosed with suspected acute appendicitis. Clinical history, examination, and relevant pre-operative investigations were performed. All patients underwent surgery, and histopathological examination of the excised appendices was conducted. Results: Acute appendicitis was confirmed in 175 patients (79.55%), with the highest incidence in individuals aged 10-19 years (54.1%). The negative appendectomy rate was 20.45%, with significantly higher rates in females (77.8%) compared to males (22.2%) (p=0.004). Younger patients (age <20 years) also showed a higher rate of negative appendectomy (33.3%) (p=0.012). Common presenting symptoms included anorexia (66.7%), elevated temperature (>99.4° F) (60%), and localized tenderness in the right iliac fossa (77.8%). Of the 64 patients who underwent pre-operative ultrasound, 63% experienced negative appendectomy. Histopathological examination revealed that 45 patients (20%) were diagnosed as not having appendicitis, with alternative conditions identified in several cases. Conclusions: The study highlights a significant rate of negative appendectomies, particularly in younger females. While clinical judgment plays a crucial role in diagnosis, the findings suggest a need for enhanced diagnostic imaging techniques to reduce unnecessary surgical interventions.

P1227 Predictors of biologics/JAKi use, surgeries, and hospitalisations in a newly diagnosed cohort of IBD patients: Long-term outcomes from the nationwide EpidemIBD study of GETECCU

Abstract Background Factors influencing the exposure to targeted therapies (biologics/JAKi), intestinal resections and hospitalisations in newly diagnosed IBD patients have been scarcely studied. Aim: To identify predictive factors of exposure to biologics/JAKi, surgeries, and hospitalisations within the first five years in IBD patients. Methods Prospective, population-based nationwide registry. Adult patients diagnosed with IBD [Crohn’s disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)] during 2017 in the 17 Spanish regions were included. Patients who consented were followed-up for 5 years after diagnosis. Multivariate analyses were performed to identify the predictive factors for biologics/JAKi use, surgeries, and hospitalisations. To this end, only abdominal surgeries were analysed, and early treatment with immunomodulators or biologics/JAKi drugs were considered if these had been prescribed within the first six months of diagnosis. Results A total of 1,526 patients diagnosed with CD and 1,633 with UC were included (figure 1). The cumulative incidence of exposure to biologics/JAKi drugs, surgeries, and hospitalisations were analysed, and predictive factors were identified. Regarding the predictors of exposure to biologics/JAKi treatments, we observed that younger age, more aggressive phenotype of CD and greater extent of UC were associated with a higher risk of exposure (table 1). Furthermore, smoking was associated with a higher likelihood of exposure to biologics/JAKi drugs in patients with CD (HR=1.33, 95%CI=1.11-1.60) while in UC patients it was associated with a lower risk (HR=0.56, 95%CI=0.35-0.89). Concerning surgeries (table 1), early treatment with immunomodulators was associated with a lower risk in patients with CD (HR=0.33, 95%CI=0.22-0.49), whereas early use of biologics/JAKi drugs was associated with a higher likelihood of surgery in patients with UC (HR=11.86, 95%CI=4.62-30.42). Finally, the exposure to biologics/JAKi drugs was associated with a lower risk of hospital admissions both in patients with CD (HR=0.37, 95%CI=0.24-0.56) and UC (HR=0.45, 95%CI=0.22-0.91) (table 1). Conclusion The exposure to biologics/JAKi drugs is mediated by the more aggressive phenotype of CD, greater extent of UC, and younger patient age. The use of biologics/JAKi drugs, as currently practiced, is associated with a lower risk of hospitalisations but does not reduce the need for surgery, even when administered early. There is an unmet need for more accurate identification of patients who require these treatments to modify the natural course of the disease.

Development and validation of a dynamic nomogram to predict alexithymia in young and middle aged stroke patients

Alexithymia, characterized by difficulty in expressing and recognizing emotions, is prevalent among young and middle-aged stroke survivors and can significantly impact rehabilitation outcomes. This study aims to develop and validate a dynamic nomogram to predict the risk of alexithymia in this population. This cross-sectional study was conducted from November 2022 to August 2023 at two tertiary hospitals in Jinzhou City and Cangzhou City, enrolling 319 patients. Predictive factors for alexithymia, such as Activities of Daily Living (ADL) scores, social support levels, lesion location, educational background, and National Institutes of Health Stroke Scale (NIHSS) scores, were identified through univariate and multivariate analyses. These factors were integrated into a web-based dynamic nomogram. The model’s accuracy was evaluated using Receiver Operating Characteristic (ROC) curves and 1000 bootstrap resamples. In the training cohort, 47.8% of patients were diagnosed with alexithymia. The nomogram demonstrated excellent fit and reliability, with an Area Under the Curve (AUC) of 0.837 (95% CI: 0.787–0.889) in the training cohort and 0.847 (95% CI: 0.767–0.928) in the validation cohort, enabling reliable early detection of alexithymia. The dynamic nomogram provides healthcare professionals with an important tool for early detection and management of alexithymia in young and middle-aged stroke survivors. While the model shows high predictive accuracy, its applicability may be limited to similar clinical settings. Future studies should evaluate its utility across diverse healthcare systems. This tool has the potential to significantly improve rehabilitation outcomes by supporting personalized therapeutic strategies and interventions.

Predictive value of enhanced corneal biomechanical parameters for ectasia progression.

To determine whether corneal biomechanical parameters can predict ectasia progression. Retrospective observational study. The baseline corneal biomechanical parameters of 64 eyes of 41 young patients (age, < 25 years at the first visit) who were diagnosed with keratoconus (KC) or suspected KC at Osaka University Hospital and followed up for more than two years were reviewed. Suspected KC was defined as borderline cases with no definitive clinical or topographical abnormalities in both eyes. The eyes were divided into progressed (P) and non-progressed (NP) groups using the ABCD grading system of Scheimpflug-based tomography. The Scheimpflug-based corneal biomechanical parameters evaluated included deformation amplitude ratio within 2mm, integrated radius, Ambrósio relational thickness to the horizontal profile, stiffness parameter at the first applanation, stress-strain index, E-staging, and Corvis Biomechanical Index. The optimized tomographic/biomechanical index (TBIv2), Belin/Ambrósio Enhanced Ectasia Deviation (BAD-D), and inferior-superior axial steepening values from Scheimpflug-based tomography were also evaluated. Twenty-three and 41 eyes were categorized into the P and NP groups, respectively. Logistic regression analysis showed that age, BAD-D, and TBIv2 could predict ectasia progression. The specificity, sensitivity, and area under the receiver operating characteristic curve (AUROC) values for BAD-D combined with age were 0.82, 0.60, and 0.83, respectively, whereas those for TBIv2 combined with age were 0.65, 0.82, and 0.82, respectively. Baseline TBIv2 is a potentially useful predictive marker for ectasia progression in young patients, whereas baseline BAD-D could be used for establishing a definitive diagnosis.

Photobiomodulation Therapy for Neurosensory Disturbances in Orthognathic Surgery Patients: A Systematic Review.

Sensory disturbances and acquired paresthesia constitute a significant proportion of complications following orthognathic surgery. This systematic review examines the application of photobiomodulation (PBM) in managing these complications and its efficacy in promoting sensory recovery. In November 2024, a comprehensive digital search was performed across reputable databases, including PubMed, Web of Science, and Scopus, using carefully selected search terms: "orthognathic surgery" AND (physiotherapy OR physical therapy OR laser OR LLLT OR PBM OR light OR LED OR acupuncture) AND (nerve OR neurosensory OR paresthesia). The search adhered to the PRISMA guidelines. Of the 424 articles initially identified, 14 met the inclusion criteria and were included in the review. The review focused on diode laser therapy for treating inferior alveolar nerve injuries, with most studies targeting this nerve and exploring diverse wavelengths, protocols, and surgical contexts, including orthognathic surgeries. Significant improvements were observed in tactile sensitivity, pain perception, and mechanical responsiveness. Factors such as earlier initiation of therapy, younger patient age, and higher treatment frequency were associated with improved outcomes. Low-level laser therapy emerges as a safe and effective intervention for enhancing neurosensory recovery following orthognathic surgery. However, the development of standardized treatment protocols and the conduct of larger-scale clinical trials are essential to optimize their clinical application.

Untreated and uncontrolled hypertension in Japanese patients with spontaneous intracerebral hemorrhage.

Hypertension (HT) is the most attributable and modifiable risk factor for spontaneous intracerebral hemorrhage (SICH). However, epidemiological data on blood pressure (BP) control before SICH and its relationship to patient lifestyles are lacking. This study prospectively enrolled patients with acute SICH from six stroke centers in Tochigi, Japan. BP control and patient lifestyles were investigated using a questionnaire conducted on patients and their families. A total of 365 patients were analyzed, 270 (74.0%) of whom had HT and 198 (54.2%) untreated HT. The prevalence of untreated HT was much higher in younger patients and decreased with age (79.0%, 71.8%, 62.2%, 44.8%, and 31.0% in those aged <50, 50-59, 60-69, 70-79, and ≥80 years, respectively). Patients with untreated HT were significantly less likely have a family doctor and attended fewer annual health checkups than did those with treated or no HT. Untreated HT with awareness was much higher in younger and middle-age men than in women, whereas untreated HT without awareness was much higher in younger women than in men. Among patients who received antihypertensives, the prevalence of well-controlled HT was also very low, especially in younger patients (20.0% and 23.5% in those aged <50, and 50-59 years, respectively). In-hospital mortality was much higher in younger patients (age <70 years) with untreated than with treated or no HT. Untreated and uncontrolled HT were highly detected and seemed to be important targets for the primary prevention of Japanese SICH. Different strategies to improve BP control are warranted for each generation and sex.

Effect of Cariprazine on Outcomes in Older-aged and Younger-aged Patients with Bipolar I Disorder: A Post-hoc Analysis.

To evaluate cariprazine in adults with older- and younger-age bipolar I disorder (OABD-I and YABD-I) and compare treatment effects between them. Pooled post-hoc analysis of studies in depressive or acute manic/mixed episodes associated with bipolar I disorder. 475/1383 patients (34.3%) in 3 depression trials and 238/1037 patients (23.0%) in 3 manic/mixed trials were OABD-I. Depression: placebo, cariprazine 1.5 mg/day, 3.0 mg/day, pooled 1.5-3.0 mg/day. Manic/mixed: placebo, cariprazine 3.0-6.0 mg/day, and 9.0-12.0 mg/day. Montgomery-Åsberg Depression Rating Scale (MADRS), Clinical Global Impression of Severity (CGI-S), and Young Mania Rating Scale (YMRS). In bipolar I depression, mean change from baseline in MADRS was significantly greater for the pooled cariprazine group vs. placebo in OABD-I (-13.72 vs. -11.98; p < 0.05) and for each cariprazine group vs. placebo among YABD-I. There was no significant difference in treatment effect between OABD-I and YABD-I for either individual cariprazine group vs. placebo. For mania/mixed states, mean change in YMRS was significantly greater for cariprazine 3.0-6.0 mg/day vs. placebo in OABD-I (-19.04 vs. -12.45; p < 0.001) and for both cariprazine groups in YABD-I (-12.49, -19.66 and -18.05 for placebo, cariprazine 3.0-6.0 mg/day and 9.0-12.0 mg/day, respectively [both p < 0.0001 vs. placebo]). There was no significant difference in treatment effect between OABD-I and YABD-I for cariprazine 3.0-6.0 mg/day vs. placebo; there was a significantly higher treatment effect for cariprazine 9.0-12.0 mg/day vs. placebo in the YABD-I subpopulation vs. OABD-I (4.20; p < 0.05). Cariprazine appears to be effective for both depressive and manic/mixed episodes of bipolar I disorder, regardless of age.

Global trends in surgical approach to neonatal brachial plexus palsy: a systematic review.

We analyzed trends in age at surgery and surgical approach over time and geography. We performed a systematic review according to PRISMA-IPD guidelines to include individual patient data. Collected data included age at surgery, location of surgery, and surgical approach. The surgical approach was independently categorized as the exploration of the brachial plexus (EBP) or nerve transfer without root exploration (NTwoRE). EBP was defined as exploring the brachial plexus in the supraclavicular fossa and applying a choice of coaptation procedures. NTwoRE included those sourcing donor nerves from, or entirely occurring outside of the plexus without exploring the root of the brachial plexus. Regression analysis of age at surgery 1985-2020 showed that age at BPBI surgery is rising (p < 0.05). Surgery was performed at a younger age in patients from Europe (7.06 ± 7.77 months) and Asia (7.58 ± 5.33 months) than those from North America (10.44 ± 5.01 months) and South America (14.71 ± 4.53 months) (p < 0.05). NTwoRE was more common in North America (37%) and least common in Europe (12%). Age at EBP was 7.2 ± 5.77 months, and age at NTwoRE was 15.85 ± 13.18 months (p < 0.05). The incidence of NTwoRE is increasing time. Age at NBPP surgery is increasing over time. Regional differences exist in age at NBPP surgery. Approaches to NBPP surgery that avoid exploration of BP roots are becoming more popular. Age at EBP is lower than age at NTwoRE.

Clonal Hematopoiesis of Indeterminate Potential in Crohn's Disease and Ulcerative Colitis.

Clonal hematopoiesis of indeterminate potential (CHIP) is the presence of somatic mutations in myeloid and lymphoid malignancy genes in the blood cells of individuals without a hematologic malignancy. Inflammation is hypothesized to be a key mediator in the progression of CHIP to hematologic malignancy and patients with CHIP have a high prevalence of inflammatory diseases. This study aimed to identify the prevalence and characteristics of CHIP in patients with inflammatory bowel disease (IBD). We analyzed whole-exome sequencing data from 587 Crohn's disease (CD), 441 ulcerative colitis (UC), and 293 non-IBD controls to assess CHIP prevalence and used logistic regression to study associations with clinical outcomes. Older UC patients (age > 45) harbored increased myeloid-CHIP mutations compared to younger patients (age ≤ 45) (P = .01). Lymphoid-CHIP was more prevalent in older IBD patients (P = .007). Young CD patients were found to have myeloid-CHIP with high-risk features. Inflammatory bowel disease patients with CHIP exhibited unique mutational profiles compared to controls. Steroid use was associated with increased CHIP (P = .05), while anti-TNF therapy was associated with decreased myeloid-CHIP (P = .03). Pathway enrichment analyses indicated an overlap between CHIP genes, IBD phenotypes, and inflammatory pathways. Our findings underscore a connection between IBD and CHIP pathophysiology. Patients with IBD and CHIP had unique risk profiles, especially among older UC patients and younger CD patients. These findings suggest distinct evolutionary pathways for CHIP in IBD and necessitate awareness among IBD providers and hematologists to identify patients potentially at risk for CHIP-related complications including malignancy, cardiovascular disease, and acceleration of their inflammatory disease.

A Risk Score to Identify Low Bone Mineral Density for Age in Young Patients with Anorexia Nervosa.

Developing a scoring assessment tools for the determination of low bone mass for age at lumbar spine and hip in patients with anorexia nervosa (AN). The areal bone mineral density (aBMD) was determined with dual-energy X-ray absorptiometry (DXA). In 331 women with AN and 121 controls, aged from 14.5 to 34.9 years, univariate and multivariate logistic regression analyses were performed to address the association of Z-score aBMD evaluated at lumbar spine and hip with several parameters. For the lumbar spine and hip, the three risk factors significantly and independently associated with Z-score aBMD were age of patients (variable in class ≥20 year vs. <20 year), minimal disease-related BMI (continuous variable), and duration of amenorrhea without contraceptive use (variable in class ≥18 months vs. <18 months), with close values for the odds ratio for the two bone sites. A simple risk score equation was developed and tested combining only these three parameters. The AUC's measuring the score's performance were, respectively, 0.85 [95% CI: 0.79-0.90] with a sensitivity of 83% and specificity of 71%, and 0.82 [95% CI: 0.76-0.86] with a sensitivity of 92% and specificity of 55% to detect low aBMD in lumbar spine and hip. The cut-off values for low bone mass for age were 0.9 and 1.33 for the two bone sites. The prediction model revealed that a minimum of 83% of the patients presenting low bone mass for age were correctly identified. the study presents for the first time a risk score for diagnosing low bone mass for age in young patients with AN. Considering its excellent sensitivity, and its ease of use, requiring only three parameters that are well identified in this disease, this new score may be useful in clinical settings when DXA scans are not feasible.

CLINIC, DIAGNOSIS AND EFFICIENCY OF NONINVASIVE METHOD OF TREATMENT YOUNG CHILDREN WITH HAEMORRHOIDS

Hemorrhoids have been known since ancient times. They have always been considered the prerogative of adult patients. Methods of conservative and surgical treatment of hemorrhoids in adults are still used in children and often have negative results. Pediatric surgical practice has not optimized methods of diagnosis and treatment of hemorrhoids in infants and preschool children. Materials and methods. The work was based on retrospective and prospective analysis of medical records and case histories of 112 children with hemorrhoids treated in the last 11 years. The number of patients under 1 year of age was 4 (0.4%); 1-3 years - 30 (26.4%); 3-6 years - 50 (44.6%); 7-12 years - 16 (14.2%); 13-18 years - 12 (10.7%). External hemorrhoids were found in 107 (95.5%), internal hemorrhoids in 4 (3.8%) and combined hemorrhoids in 1 (0.9%) patient. There were 70 (62.5%) boys and 42 (37.5%) girls. All cases underwent general clinical and laboratory examination, orthostatic exercise (squatting), rectal palpation, anoscopy and rectoscopy. Statistical processing of the research materials was carried out using the method of variance statistics. All values in the work are presented in the form of arithmetic mean with calculation of standard deviation within the confidence interval. For all compared values the achieved level of significance (p) was considered statistically reliable - &lt; 0.05. Student's t-distribution was used to compare data with normal distribution of means. When comparing 2 related groups, calculations were performed using Student's paired t-criterion. Microsoft Excel and Statistica computer programs were used for statistical data processing. Results and discussion. This paper presents clinical material from the examination and treatment of 112 children with hemorrhoids over the past 11 years. The authors compare the characteristics of the etiopathogenesis of hemorrhoids in children from the literature and their own research data. The proposed non-invasive compression methods in the complex treatment of hemorrhoids in children are more effective in children of early and preschool age. A study of long-term results of complex conservative treatment of 84 patients of young age with hemorrhoids showed good results in 86,9%, satisfactory - in 9,5% and unsatisfactory (recurrence) - in 3,6% of patients. Surgical treatment of hemorrhoids in children was used only when conservative treatment was unsuccessful in 11 (12.6%) patients, with good long-term results in all cases. Indications for hemorrhoidectomy were: frequent prolapse of hemorrhoids (HU). After surgical treatment, good results were obtained in all cases; no recurrence was observed. The optimization of conservative and surgical treatment, respecting the age characteristics of children, led to good results. Conclusions: 1. Examination of children with GU enlargement with the use of additional methods (ultrasound, RRS, FACS, PCI) of research allows to reveal and treat concomitant intestinal pathologies, which are the causes of secondary transient hemorrhoids development. For children of preschool age the most effective non-invasive method of treatment is rectal balonocompression. 3. After complex conservative treatment with rectal balonocompression of children with hemorrhoids good results were observed in 86,9% of children, satisfactory - in 9,5% and unsatisfactory - in 3,6%.

Diabetes and Cataracts Development-Characteristics, Subtypes and Predictive Modeling Using Machine Learning in Romanian Patients: A Cross-Sectional Study.

Background and Objectives: Diabetes has become a global epidemic, contributing to significant health challenges due to its complications. Among these, diabetes can affect sight through various mechanisms, emphasizing the importance of early identification and management of vision-threatening conditions in diabetic patients. Changes in the crystalline lens caused by diabetes may lead to temporary and permanent visual impairment. Since individuals with diabetes are at an increased risk of developing cataracts, which significantly affects their quality of life, this study aims to identify the most common cataract subtypes in diabetic patients, highlighting the need for proactive screening and early intervention. Materials and Methods: This study included 201 participants with cataracts (47.6% women and 52.4% men), of whom 105 also had diabetes. With the use of machine learning, the patients were assessed and categorized as having one of the three main types of cataracts: cortical (CC), nuclear (NS), and posterior subcapsular (PSC). A Random Forest Classification algorithm was employed to predict the incidence of different associations of cataracts (1, 2, or 3 types). Results: Cataracts have been encountered more frequently and at a younger age in patients with diabetes. CC was significantly more frequent among patients with diabetes (p < 0.0001), while the NS and PSC were only marginally, without statistical significance. Machine learning could also contribute to an early diagnosis of cataracts, with the presence of diabetes, duration of diabetes, or diabetic polyneuropathy (PND) having the highest importance for a successful classification. Conclusions: These findings suggest that diabetes may impact the type of cataract that develops, with CC being notably more prevalent in diabetic patients. This has important implications for screening and management strategies for cataract formation in diabetic populations.

Study on clinical features of early death in older patients with acute promyelocytic leukemia.

This study aimed to analyze the baseline clinical characteristics, as well as the clinical features and risk factors of early death (ED) in older patients with acute promyelocytic leukemia (APL). A retrospective analysis was conducted on 198 consecutive older patients (age ≥ 50 years) with newly diagnosed APL who received arsenic trioxide alone as induction therapy, with 354 younger patients (age < 50 years) as controls. Ten easily obtainable clinical parameters were selected. Compared with the younger group, the older group had less fever, lower white blood cell (WBC) count, lower levels of albumin, and higher levels of creatinine upon admission. While the younger group had higher levels of aspartate aminotransferase and lower levels of fibrinogen (all P < 0.05). The ED rate was significantly higher in the older group (21.7% vs. 12.4%; P = 0.004). The causes of ED in the older group were bleeding, infection, embolism, differentiation syndrome, and others, in order of incidence. The cumulative incidence of ED due to infection (P = 0.0003) and embolism (P = 0.034) was significantly higher in the older group. For the older patients, independent risk factors for ED were WBC count > 5.9 × 109 /L, albumin < 35.85g/L, creatinine > 72.9 µmol/L and fibrinogen < 1.137g/L; independent risk factor for bleeding ED was WBC count > 6.2 × 109 /L; while independent risk factors for infection ED were albumin < 36.55g/L and fibrinogen < 1.035g/L. The baseline clinical characteristics, the clinical features and risk factors of ED in older APL patients were all quite different from those in younger patients, so research specifically targeting older patients with APL is very necessary.

Long-Term Survival of Methotrexate as First-Line Therapy in Rheumatoid Arthritis, Psoriatic Arthritis and Undifferentiated Arthritis.

Background/Objectives: In the era of biotechnological drugs, methotrexate (MTX) still represents the first-line treatment in chronic inflammatory arthritis, such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), and undifferentiated arthritis (UA). The aim of our study was to evaluate the persistence of MTX as a first-line treatment in a group of patients with chronic inflammatory arthritis. Methods: We conducted a retrospective analysis of a database of outpatients diagnosed with RA, PsA, or UA who visited our Rheumatology Clinic from January 2014 to January 2022. Key demographic and clinical data, including information on comorbidities and treatments, were routinely collected. Kaplan-Meier (KM) curves were used to determine the persistence of MTX during follow-up. Results: A total of 242 patients with chronic inflammatory arthritis who initiated MTX as first-line therapy and had available clinical data were included. Of these, 130 (53.7%) had RA, 82 (33%) had PsA, and 30 (16.3%) had UA. Overall, the survival rate of MTX at 24 months of follow-up was approximately 60%, while at 48 months and 96 months, it was 40% and 20%, respectively. A statistically significant difference was found between RA and PsA compared to UA (Chi-square test = 14.84; p = 0.001). When comparing the KM survival curves of MTX between male and female patients, obese and non-obese individuals, as well as older (age ≥ 50 years) and younger patients (age < 50 years), no statistically significant differences were observed in any of the comparisons. Conclusions: Our study confirmed the efficacy and overall safety of MTX in RA and PsA, with good persistence even over the long term.

Optical Microangiography and Progressive Retinal Nerve Fiber Layer Loss in Primary Angle-closure Glaucoma

Precis Younger patient age (coefficient: 0.10, P=0.04) and greater peak IOP during follow-up (coefficient: -0.14, P=0.03), but not baseline optical microangiography parameters, were significantly associated with a faster rate of RNFL loss in mild-moderate PACG. Purpose: To evaluate the association between optical microangiography (OMAG) measurements and progressive retinal nerve fiber layer (RNFL) loss in primary angle-closure glaucoma (PACG). Methods: In a prospective study, 45 eyes of 30 PACG patients (86 hemifields) with mild to moderate functional damage were longitudinally studied for at least 2 years and with a minimum of 3 optical coherence tomography (OCT) examinations. OMAG imaging was performed at the baseline visit. Effect of clinical parameters (age, gender, presence of systemic diseases, central corneal thickness, mean, peak and fluctuation of intraocular pressure during follow-up), baseline hemifield mean deviation (MD) and baseline OMAG (quadrant peripapillary and macular perfusion density [PD]) on the rate of RNFL change was evaluated using linear mixed models. Results: Average (±SD) hemifield MD, RNFL thickness, peripapillary PD and macular PD of the analyzed quadrants at baseline were -6.0±3.4 dB, 89±21 µm, 40.1±3.5% and 29.6±10.3%, respectively. Rate of quadrant RNFL change was -2.5±1.7 µm/year. Multivariate mixed models showed that younger patient age (coefficient: 0.10, P=0.04) and higher peak IOP during follow-up (coefficient: -0.14, P=0.03) were significantly associated with a faster rate of RNFL loss. Conclusions: Younger patient age and greater peak IOP during follow-up were significantly associated with a faster rate of RNFL loss in PACG patients with mild to moderate severity of functional damage. None of the OMAG parameters at baseline were associated with RNFL thinning suggesting a limited role of OCTA imaging in predicting structural progression in mild-moderate PACG.

Spatial QRS-T angle can indicate presence of myocardial fibrosis in pediatric and young adult patients with hypertrophic cardiomyopathy.

Myocardial fibrosis, expressed as late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR), is an important risk factor for malignant cardiac events in hypertrophic cardiomyopathy (HCM). However, CMR is not easily available, expensive, also needing intravenous access and contrast. To determine if derived vectorcardiographic spatial QRS-T angles, an aspect of advanced ECG (A-ECG), can indicate LGE to appropriately prioritize young HCM-patients for CMR. Young patients (age 7-31years) with clinical HCM (N=19) or genotype-positive but phenotype-negative (G+ P-) results (N=6) and nine healthy volunteers were evaluated for LGE by CMR at a single centre between 2011 and 2018. A-ECG was performed within 4months before and 6months after CMR and evaluated for spatial mean and peaks QRS-T angles. ECG Risk-score and frontal, two-dimensional QRS-T angle were also calculated from the 12‑lead ECG. All QRS-T angles were significantly higher in the HCM group with LGE as compared to the HCM group without LGE, and the G+ P- and Healthy groups. Only HCM-patients showed LGE (11/19). The optimal cut-offs for indicating LGE were>50° for the spatial peaks (AUC=0.98 [95%CI 0.95-1.00], sensitivity 100%, specificity 93%; p<0.001), >80° for the spatial mean (AUC=0.91; p<0.001), and>60° for the frontal QRS-T angles (AUC=0.85; p<0.001), and>2 points for an established ECG risk-score (AUC=0.90, p<0.001). A spatial peaks QRS-T angle >50° has excellent sensitivity and specificity as a marker of myocardial fibrosis in a young patients with HCM, and can be useful for management and follow-up of such patients.

Malignant melanotic nerve sheath tumor

Malignant melanotic nerve sheath tumor, previously known as melanotic schwannoma, is a rare variant of peripheral nerve sheath tumor composed of melanin-producing Schwann cells and clinically misdiagnosed as melanoma. Malignant melanotic nerve sheath tumor is a rare tumor with uncertain biological behavior and variable treatment recommendations. Despite the histological features that seem benign, with a low proliferation index, the clinical course of this tumor often becomes malignant, with a high frequency of local relapses and the presence of tumor metastasis signs. Distinctive features of malignant melanotic tumor of the nerve sheath are a relatively young age of patients, the presence of the Carney complex signs and psammomatous bodies in the tumor. The article presents a case of malignant melanotic tumor of the nerve sheath localized in the neck with a recurrent course. In the described clinical observation, the patient underwent surgical treatment twice. Microscopic and immunohistochemical analysis of postoperative materials gave a positive result for melanoma markers and showed the absence of psammoma bodies and low mitotic activity. The clinical course of the disease was malignant, with the appearance of a relapse in the postoperative scar. Diagnosis of malignant melanotic tumor of the nerve sheath is a complex task, both from the radiological and pathological points of view. Communication between the surgeon, radiologist and pathologist, understanding the anatomical relationships of the lesion and careful attention to the histological findings are critical to making the correct diagnosis.

Analysis of results of radiotherapy for oropharyngeal cancer.

Smoking and alcohol consumption remain the two most important risk factors for the development of oropharyngeal tumours, but there is an increasing number of younger patients (age <50 years) with human papillomavirus (HPV) association origin, also known as positivity. The role of radiotherapy (RT) in the treatment of this disease is paramount. To describe the radiotherapy results for oropharyngeal tumours and to search for prognostic parameters that influence the response of these malignant lesions to radio-chemotherapy. 95 patients underwent definitive radio- or radio-chemotherapy (RCT) for histologically squamous cell, oropharyngeal carcinoma at our Institute between 1January 2019 and 31 December 2020, of which 51 (54%) received the latter. The mean age was 61.9 years (37-82 years) and the male-female ratio was 69:26. The average total dose was 69 Gy (range: 54-70 Gy). The 5-year local control (LC), cancer-specific survival (CCS), and overall survival (OS) calculated by the Kaplan-Meier method were 71, 69, and 58%, respectively. Forty-four cases (46%) were confirmed tohave HPV involvement. HPV positive (+) tumours showed significantly better behaviour compared to HPV negative (-) cases in LC, CCS and OS. Smoking had a significant negative effect on cure rates: LC, CCS and OS were better in non-smokers. A significant negative effect of smoking on survival was alsoobserved in HPV-associated cases. For HPV- lesions, RCT had a stronger effect on LC than RT alone(64 vs43%, P = 0.03). HPV-associated malignancies show better survival outcomes toradio ± chemotherapy than their HPV- counterparts. In all cases, smoking worsens the response to treatment. For HPV- tumours, chemotherapy with radiation, compared to irradiation alone, has a more significant effect on survival outcomes, whereas for HPV+ tumours this effect is less pronounced.