Clinical Associations Research Articles

Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) associated with Paracentral Acute Middle Maculopathy (PAMM) and Cilioretinal Artery Occlusion (CILRAO): multimodal imaging of a newly described clinical association.

To report multimodal imaging features of a novel association of non-arteritic anterior ischemic optic neuropathy (NAION), paracentral acute middle maculopathy (PAMM), and cilioretinal artery occlusion (CILRAO). A 74-year-old male patient presented complaining of an acute subjective decline in visual acuity in the right eye over the previous days. This patient underwent a comprehensive ophthalmological assessment, including multimodal retinal imaging and visual field test. The eye examination revealed yellowish optic disc edema in the right eye with peripapillary hemorrhages and a whitish lesion extending from the temporal margin of the optic nerve head towards the macula. Multimodal imaging confirmed the diagnosis of NAION in the right eye. Notably, the structural B-scan and en face OCT images revealed hyperreflective areas in the inner and mid retinal layers, indicating an association with CILRAO and PAMM. We herein describe the clinical findings of a previously unreported association among NAION, CILRAO and PAMM.

Macrophages as a Source and Target of GDF-15.

Growth differentiation factor 15 (GDF-15) is a multifunctional cytokine that belongs to the transforming growth factor-beta (TGF-β) superfamily. GDF-15 is involved in immune tolerance and is elevated in several acute and chronic stress conditions, often correlating with disease severity and patient prognosis in cancer172 and metabolic and cardiovascular disorders. Despite these clinical associations, the molecular mechanisms orchestrating its effects remain to be elucidated. The effects of GDF-15 are pleiotropic but cell-specific and dependent on the microenvironment. While GDF-15 expression can be stimulated by inflammatory mediators, its predominant effects were reported as anti-inflammatory and pro-fibrotic. The role of GDF-15 in the macrophage system has been increasingly investigated in recent years. Macrophages produce high levels of GDF-15 during oxidative and lysosomal stress, which can lead to fibrogenesis and angiogenesis at the tissue level. At the same time, macrophages can respond to GDF-15 by switching their phenotype to a tolerogenic one. Several GDF-15-based therapies are under development, including GDF-15 analogs/mimetics and GDF-15-targeting monoclonal antibodies. In this review, we summarize the major physiological and pathological contexts in which GDF-15 interacts with macrophages. We also discuss the major challenges and future perspectives in the therapeutic translation of GDF-15.

Clinical Features, Investigative Profile and Association with Metabolic Syndrome in Facial Acanthosis Nigricans: A Case–Control Study in Indian Patients

Objectives: The present study was undertaken to study the clinical profile and laboratory abnormalities in patients with facial acanthosis nigricans (FANs). The significance of FAN as a marker of insulin resistance (IR), metabolic syndrome (MS) and its components was determined by comparing with controls without FAN. Materials and Methods: Fifty clinically diagnosed cases of FAN of all ages and both sexes were enrolled. Age- and sex-matched obese patients without FAN were included as controls. Waist circumference, blood pressure and body mass index were measured. Venous samples were taken from all patients and controls for measuring fasting glucose level, fasting insulin levels and fasting lipid profile. Statistical analysis was done using the Chi-square test and unpaired t-test. Results: The prevalence of hypertension, dysglycaemia, hyperlipidaemia, elevated Homeostatic Model Assessment for IR (HOMA-IR) and MS was significantly higher in cases of FAN than controls (P < 0.05). The mean levels of fasting blood sugar, HOMA-IR, hypertension, high-density lipoprotein and serum triglycerides were significantly higher in patients of FAN than controls (P < 0.05). The odds ratio for FAN cases developing MS was determined to be 5.31. Conclusion: FAN may be considered as a significant clinical marker of IR with increased risk for MS and its component when compared to controls. All patients with FAN should be considered for a thorough biochemical workup to rule out MS. In all detected cases, it is prudent to initiate prompt remedial measures including lifestyle changes and pharmacotherapy to prevent long-term morbidity and mortality.

Laboratory features in acute paediatric poisoning with liquid laundry detergent capsules: a seven-year retrospective study in Romania

Introduction The epidemiological and clinical characteristics of acute poisoning with liquid laundry detergent capsules have been comprehensively reported. However, studies of laboratory test results in these exposures are uncommon. This study analyzed the impact of the ingestion of liquid laundry detergent capsules on admission laboratory tests in paediatric patients. Methods This retrospective study was conducted in the clinical toxicology unit of a paediatric poison centre between 2015 and 2021. Paediatric patients (less than 18 years of age) who ingested liquid laundry detergent capsules were included. The relationship between the European Association of Poisons Centers and Clinical Toxicologists/European Commission/International Programme on Chemical Safety Poisoning Severity Score and admission laboratory test results was assessed using Fisher’s exact test or analysis of variance. Results A total of 156 patients were included in the study. A considerable proportion of patients presented with leucocytosis, acidosis, hyperlactataemia or base deficit. The median values of white blood cell count (P = 0.042), pH (P = 0.022), and base excess (P = 0.013) were significantly different among the Poisoning Severity Score groups. Hyperlactataemia was strongly associated with the Poisoning Severity Score (P = 0.003). Discussion Leucocytosis is a non-specific marker of severity following ingestion of liquid laundry detergent capsules. The incidence of metabolic acidosis and hyperlactataemia was higher in this study than in previous reports, but these metabolic features were not related to the severity of exposure. The exact mechanisms of toxicity are not yet known, but the high concentration of non-ionic and anionic surfactants, as well as propylene glycol and ethanol, in the capsule are likely contributing factors. Conclusions Pediatric patients who ingest liquid laundry detergent capsules may develop leucocytosis, metabolic acidosis, hyperlactataemia, and a base deficit.

DPP2/7 is a Potential Predictor of Prognosis and Target in Immunotherapy in Colorectal Cancer: An Integrative Multi-omics Analysis.

Colorectal cancer (CRC) ranks among the leading causes of cancerrelated deaths. This study aimed to illuminate the relationship between DPP7 (also known as DPP2) and CRC through a combination of bioinformatics and experimental methodologies. A multi-dimensional bioinformatic analysis on DPP7 was executed, covering its expression, survival implications, clinical associations, functional roles, immune interactions, and drug sensitivities. Experimental validations involved siRNA-mediated DPP7 knockdown and various cellular assays. Data from the Cancer Genome Atlas (TCGA) identified high DPP7 expression in solid CRC tumors, with elevated levels adversely affecting patient prognosis. A shift from the N0 to the N2 stage in CRC was associated with increased DPP7 expression. Functional insights indicated the involvement of DPP7 in cancer progression, particularly in extracellular matrix disassembly. Immunological analyses showed its association with immunosuppressive entities, and in vitro experiments in CRC cell lines underscored its oncogenic attributes. DPP7 could serve as a CRC prognosis marker, functioning as an oncogene and representing a potential immunotherapeutic target.

Systematic Reporting of Eosinophils in Transbronchial Biopsies After Lung Transplantation Defines a Distinct Inflammatory Response

Background. Descriptions of eosinophils in transbronchial biopsy (TBBx) pathology reports after lung transplantation (LTx) are associated with poor long-term outcomes. The absence of routine reporting and standardization precludes accurate assessment of this histologic predictor. A systematic reporting scheme for the presence of TBBx eosinophils after LTx was implemented. This report aims to assess this scheme by describing the presence, pattern, and gradation of TBBx eosinophils and clinical associations. Methods. A prospective cross-sectional study of all TBBx reports was performed including all patients presenting for a surveillance or diagnostic TBBx between January 2020 and June 2023. Each TBBx was systematically reported in a blinded manner. Mixed-effects logistic regression was performed to measure the association between concurrent clinical and histologic features, and the presence of TBBx eosinophils. Results. A total of 410 TBBx reports from 201 patients were systematically reported. In 43.8% recipients, any TBBx eosinophils were detected and in 17.1% recipients, higher-grade eosinophils (≥3 per high power field) were present. Adjusted analysis showed that retransplantation, A- and B-grade cellular rejection, positive bronchoalveolar lavage (BAL) bacterial microbiology, and elevated blood eosinophil count were independently associated with the presence of any TBBx eosinophils. Diagnostic “for-cause” procedures were independently associated with higher quantities of TBBx eosinophils. Conclusions. Systematic reporting demonstrates that TBBx eosinophils are a distinct inflammatory response associated with rejection, infection, and peripheral eosinophilia. Although these findings require multicenter external validation, standardized reporting for TBBx eosinophils may assist in identifying recipients at risk of poor outcomes and provides a platform for mechanistic research into their role after lung transplantation.

Multiarray screening identifies plasma proteins associated with Th17 cell differentiation and viral defense in coincident asthma and obesity.

The immunological mechanisms behind the clinical association between asthma and obesity in adolescence are not fully understood. This study aimed to find new plasma protein biomarkers associated specifically with coincident asthma and obesity in adolescents. This was a cross-sectional study in children and adolescents 10-19 years old (N = 390). Relative plasma concentrations of 113 protein biomarkers related to inflammation and immune response were determined by proximity extension assay (Target 96; Olink, Uppsala, Sweden). Differences in protein concentrations between healthy controls (n = 84), subjects with asthma (n = 138), subjects with obesity (n = 107), and subjects with both asthma and obesity (AO; n = 58) were analyzed by ANCOVA, adjusting for age and sex, and in a separate model adjusting also for the sum of specific IgE antibody concentrations to a mix of food allergens (fx5) and aeroallergens (Phadiatop). Proteins elevated in the AO group but not in the obesity or asthma groups were considered specifically elevated in asthma and obesity. Five proteins were elevated specifically in the AO group compared to controls (here sorted from largest to smallest effect of asthma and obesity combined): CCL8, IL-33, IL-17C, FGF-23, and CLEC7A. The effects of adjusting also for specific IgE were small but IL-33, IL-17C, and FGF-23 were no longer statistically significant. We identified several new potential plasma biomarkers specifically elevated in coincident asthma and obesity in adolescents. Four of the proteins, CCL8, IL-33, IL-17C, and CLEC7A, have previously been associated with viral mucosal host defense and Th17 cell differentiation.

Distinct Comorbidity Clusters in Patients With Acute Heart Failure: Data From RELAX-AHF-2

BackgroundMultimorbidity frequently occurs in patients with acute heart failure (AHF). The co-occurrence of comorbidities often follows specific patterns. ObjectivesThis study investigated multimorbidity subtypes and their associations with clinical outcomes. MethodsFrom the prospective RELAX-AHF-2 (Relaxin for the Treatment of Acute Heart Failure-2) trial, 6,545 patients (26% with HF with preserved ejection fraction, defined as LVEF ≥50%) were classified into multimorbidity groups using latent class analysis. The association between subgroups and clinical outcomes was examined. Validation of these findings was conducted in the RELAX-AHF trial, which comprised 1,161 patients. ResultsFive distinct multimorbidity groups emerged: 1) diabetes and chronic kidney disease (CKD) (often male, high prevalence of CKD and diabetes mellitus); 2) ischemic (ischemic HF); 3) elderly/atrial fibrillation (AF) (oldest, high prevalence of AF); 4) metabolic (obese, hypertensive, more often HF with preserved ejection fraction); and 5) young (fewest comorbidities). After adjusting for confounders, patients in the diabetes and CKD (HR: 1.80; 95% CI: 1.50-2.20), elderly/AF (HR: 1.42; 95% CI: 1.20-1.70), and metabolic (HR: 1.40; 95% CI: 1.20-1.80) groups had higher rates of the composite outcome than patients in the young group, primarily driven by differences in rehospitalization. Treatment allocation (placebo or serelaxin) modified these associations (Pinteraction <0.001). Serelaxin-treated patients in the young group were associated with a lower risk for all-cause mortality (HR: 0.59; 95% CI: 0.40-0.90). Similarly, patients from the RELAX-AHF trial clustered in 5 multimorbidity groups. The clinical characteristics and associations with outcomes could also be validated. ConclusionsComorbidities naturally clustered into 5 mutually exclusive groups in RELAX-AHF-2, showing variations in clinical outcomes. These data emphasize that the specific combination of comorbidities can influence adverse outcomes and treatment responses in patients with AHF.

Epidemiology, clinical features, and outcomes of intussusception in young children: A tertiary center experience

Background: Intussusception in young and old children is different. A study of clinical features, associations, and outcomes of these cases would enhance understanding to guide proper management. Objectives: Analysis of the epidemiology, associations, clinical features, and management outcomes of intussusception in children younger than 2 years. Patients and Methods: A retrospective descriptive study on intussusception patients younger than 2 years was conducted from January 2018 to December 2022 in the department of pediatric surgery at a tertiary center. Demographic details, clinical features, and management outcomes data were collected and analyzed. Results: A total of patients were 133 with mean, median, and modal age of 9.5, 7, and 6 months, respectively; the maximum incidence was in March. 81.95% of cases were idiopathic; important lead points were Meckel diverticulum, inflamed appendix, roundworm, cecal duplication, and intraluminal polyps. Two postoperative cases occurred in Wilms’ tumor and congenital diaphragmatic hernia patients, whereas two postrotavirus vaccination cases were seen. Ten (7.5%) had associated malrotation which necessitated Ladd’s procedure. Only 15 cases presenting early responded to nonoperative treatment (9/15 hydrostatic reduction and 6/15 conservative management); among late presenters, 12.71% had manual reduction, 68.64% had resection and anastomosis while in 16.95%, temporary stoma was needed. Wound infection, burst abdomen, subacute intestinal obstruction, recurrent intussusception, peristomal excoriation, and stomal prolapse were a few complications along with one death. Conclusion: Intussusception in children younger than 2 years is a heterogeneous group. Although mostly idiopathic, several associations and well-defined lead points require additional intervention. Early diagnosis and prompt intervention ensure a favorable outcome with fewer complications.

Clinical characteristics and associations with atherosclerosis among adult patients with psoriasis vulgaris: A multi-centered study in Vietnam

Clinical characteristics and associations with atherosclerosis among adult patients with psoriasis vulgaris: A multi-centered study in Vietnam

Barriers and Unmet Educational Needs Regarding Implementation of Medication Adherence Management Across Europe: Insights from COST Action ENABLE

Abstract Background Medication adherence is essential for the achievement of therapeutic goals. Yet, the World Health Organization estimates that 50% of patients are nonadherent to medication and this has been associated with 125 billion euros and 200,000 deaths in Europe annually. Objective This study aimed to unravel barriers and unmet training needs regarding medication adherence management across Europe. Design A cross-sectional study was conducted through an online survey. The final survey contained 19 close-ended questions. Participants The survey content was informed by 140 global medication adherence experts from clinical, academic, governmental, and patient associations. The final survey targeted healthcare professionals (HCPs) across 39 European countries. Main Measures Our measures were barriers and unmet training needs for the management of medication adherence across Europe. Key Results In total, 2875 HCPs (pharmacists, 40%; physicians, 37%; nurses, 17%) from 37 countries participated. The largest barriers to adequate medication adherence management were lack of patient awareness (66%), lack of HCP time (44%), lack of electronic solutions (e.g., access to integrated databases and uniformity of data available) (42%), and lack of collaboration and communication between HCPs (41%). Almost all HCPs pointed out the need for educational training on medication adherence management. Conclusions These findings highlight the importance of addressing medication adherence barriers at different levels, from patient awareness to health system technology and to fostering collaboration between HCPs. To optimize patient and economic outcomes from prescribed medication, prerequisites include adequate HCP training as well as further development of digital solutions and shared health data infrastructures across Europe.

Тактика лікування гігантської тератоми шиї в новонародженої дитини: клінічний випадок

Teratoma can be diagnosed with ultrasound examination and screening, which is carried out in intrauterine period of the fetal development. Early diagnostics of the pathology is of the great importance of its treatment. The detailed management of newborns with giant neck teratoma have not been found in current literature. Furthermore, there is no information concerning preparation of the patient for the radical operation. The aim is to present the clinical case of surgical treatment of giant neck teratoma in newborn child using EXIT-procedure (intrauterine treatment to establish a functioning airway) and angiography before the radical excision of the tumor. The clinical case describes the diagnostics and treatment of newborn child with giant neck teratoma, who was taken to the first clinical Lviv association “St. Nicholas hospital”. The tumor was diagnosed intrauterine. The child underwent EXIT-procedure. Selective angiography and embolization of carotid branches were carried out on third day after birth. The surgical intervention regarding the removal of the tumor, which was removed radically with blood loss up to 50 ml, was performed on fourth day after birth. Conclusions. Prenatal screening with alpha-protein detection in mother blood is essential for diagnostics of probable pathologies of the fetal development. EXIT-procedure has led to save lung ventilation and effective support of the cardiovascular system. The selective angiography allowed to assess the bloodstream within branches of the internal carotid artery. The embolization of the branches of the external carotid artery, which vascularized the tumor, led to minimization of the blood loss up to 50 ml. As the removal of tumor was radical, further specialized treatment was not needed. The research was carried out in accordance to principles of the Helsinki declaration. The informed consent of the child’s parents was given for conducting the research. The authors declare no conflict of interest.

Clinical Association Between Immune-related Adverse Events and Treatment Efficacy in Patients With Non-small-cell Lung Cancer Treated With Nivolumab-Ipilimumab-based Therapy.

Nivolumab and ipilimumab combination therapy has been extensively explored for the treatment of advanced non-small-cell lung cancer (NSCLC) through the pivotal phase III trials CheckMate 227 and CheckMate 9LA. However, the relationship between immune-related adverse events (irAEs) and the effectiveness of nivolumab plus ipilimumab-based therapy in a real-world clinical setting remains uncertain. We performed a retrospective analysis of 28 patients with advanced or recurrent NSCLC who underwent treatment with nivolumab plus ipilimumab, with or without platinum-doublet chemotherapy, from February 2021 to January 2023. The primary objective was to elucidate the clinical association between irAEs and treatment efficacy associated with nivolumab plus ipilimumab-based therapy. Among the 28 patients, 22 (78.6%) experienced irAEs. The median progression-free survival (PFS) was significantly longer for patients with irAEs than for those without (p=0.0158), as was overall survival (OS) (p=0.000394). The severity of irAEs had no significant influence on PFS or OS. The objective response rate tended to be higher in patients with irAEs than in those without (50.0% versus 0.0%, respectively; p=0.0549). Multivariate analysis indicated that irAE occurrence was an independent factor for improved PFS (hazard ratio=0.2084, p=0.01383) and OS (hazard ratio=0.0857, p=0.001588). Interstitial lung disease was inferior to other irAE profiles for both PFS and OS. Patients with advanced NSCLC experiencing irAEs demonstrated superior clinical outcomes when treated with nivolumab plus ipilimumab-based therapy compared with those without irAEs. However, immune-related interstitial lung disease may be less linked with PFS and OS than other irAE profiles.

Substance use disorders among armed forces veterans with gambling disorder: Insights from an inpatient treatment sample

Armed forces veterans are especially prone to experiencing a variety of addictive disorders, including gambling disorder. Even so, gambling disorder in veterans remains understudied generally, and there remain significant gaps in the research literature with regards to how gambling disorder relates to the experience and expression of comorbid substance use disorders. The present work examines the prevalence, presentation, and clinical associations of substance use disorders in U.S. Armed Forces veterans receiving inpatient treatment for gambling disorder. Participants (N = 664) were veterans from all branches of the U.S. Armed Forces receiving inpatient treatment for gambling disorder through the Department of Veteran Affairs Healthcare System. Clinical data from the time of intake was analyzed. A substantial portion of veterans (36.1%) met current criteria for an SUD, with another 16.5% reporting a history of SUD. Alcohol use disorder was the most commonly reported SUD (76.1% of those with a current SUD), with polysubstance use disorders and stimulant use disorders each occurring in at least 25% of those with SUDs. SUD status was related to greater levels of impulsivity, but there was no evidence that SUD status was related to gambling symptom severity, gambling preferences, or further psychiatric comorbidities.

Joint Hypermobility, Autonomic Dysfunction, Gastrointestinal Dysfunction, and Autoimmune Markers: Clinical Associations and Response to Intravenous Immunoglobulin Therapy.

We examined autoimmunity markers (AIM) and autonomic dysfunction in patients with chronic neurogastroenterological symptoms and their relationship to joint hypermobility/hypermobility spectrum disorder (JH/HSD). AIM positivity was defined as a diagnosis of known autoimmune/autoinflammatory disorder with at least 1 positive seromarker of autoimmunity or at least 2 positive seromarkers by themselves. Three cohorts were studied: (i) retrospective (n = 300), (ii) prospective validation cohort (n = 133), and (iii) treatment cohort (n = 40), administered open-label intravenous immunoglobulin (IVIG). AIM positivity was found in 40% and 29% of the retrospective and prospective cohorts, the majority of whom (71% and 69%, respectively) had autoinflammatory disorder. Significantly more patients with AIM had elevations of C-reactive protein (31% vs 15%, P < 0.001) along with an increased proportion of cardiovascular autonomic dysfunction (48% vs 29%; P < 0.001), small fiber neuropathy (20% vs 9%; P = 0.002), and HLADQ8 positivity (24% vs 13%, P = 0.01). Patients with JH/HSD were more likely to have AIM (43% vs 15%, P = 0.001) along with more severe autonomic and gastrointestinal (GI) symptom scores. IVIG treatment was associated with robust improvement in pain, GI, and autonomic symptoms, but adverse events were experienced by 62% of patients. Autoimmune markers and autonomic dysfunction are common in patients with unexplained GI symptoms, especially in those with JH/HSD. Many patients seem to respond to IVIG treatment, but this needs to be confirmed by controlled trials. These results highlight the need for vigilance for autoimmune and autonomic factors and JH/HSD in patients with neurogastroenterological disorders. Clinicaltrials.gov , NCT04859829.

Bicaudal D2 autoantibodies are highly specific for systemic sclerosis

Objective Autoantibodies directed against the intracellular protein bicaudal D2 (BICD2) have been identified as a specific marker of systemic sclerosis (SSc). Since autoantibodies are of value in predicting disease onset and identifying meaningful clinical subsets, as well as having prognostic value, this study aimed to establish the prevalence of BICD2 autoantibodies (anti-BICD2) in a cohort of patients with connective tissue disease and healthy controls. Method In this cross-sectional study, 363 patients with connective tissue disease (121 SSc, 141 systemic lupus erythematosus, 101 myositis, and 100 blood donors) were tested for the presence of anti-BICD2. All SSc patients were tested for specific anti-nuclear antibodies (ANAs), and clinical and laboratory associations were evaluated in the SSc patients, stratified by anti-BICD2 status. Results In the SSc cohort, 35 patients had autoantibodies directed against BICD2. The specificity of anti-BICD2 in SSc patients was 96.5%; however, the sensitivity was only 28.9%. Anti-BICD2 and centromere autoantibodies were present together in 91% of the anti-BICD2-positive SSc patients, and in none of the cases was anti-BICD2 the only antibody present. Anti-BICD2-positive patients had lower forced expiratory volume in 1 s (FEV1) (p = 0.01) and lower carbon monoxide transfer coefficient (KCO) (p = 0.01) than anti-BICD2-negative SSc patients, but they had higher forced vital capacity (p = 0.03). Conclusion Autoantibodies against BICD2 were highly specific for SSc patients. Reduced FEV1 and KCO in anti-BICD2-positive patients may indicate that the presence of anti-BICD2 is associated with altered lung function in an unknown pathophysiological manner, which awaits further elucidation.

Quality over quantity: powering neuroimaging samples in psychiatry.

Neuroimaging has been widely adopted in psychiatric research, with hopes that these non-invasive methods will provide important clues to the underpinnings and prediction of various mental health symptoms and outcomes. However, the translational impact of neuroimaging has not yet reached its promise, despite the plethora of computational methods, tools, and datasets at our disposal. Some have lamented that too many psychiatric neuroimaging studies have been underpowered with respect to sample size. In this review, we encourage this discourse to shift from a focus on sheer increases in sample size to more thoughtful choices surrounding experimental study designs. We propose considerations at multiple decision points throughout the study design, data modeling and analysis process that may help researchers working in psychiatric neuroimaging boost power for their research questions of interest without necessarily increasing sample size. We also provide suggestions for leveraging multiple datasets to inform each other and strengthen our confidence in the generalization of findings to both population-level and clinical samples. Through a greater emphasis on improving the quality of brain-based and clinical measures rather than merely quantity, meaningful and potentially translational clinical associations with neuroimaging measures can be achieved with more modest sample sizes in psychiatry.

Oral pimonidazole unveils clinicopathologic and epigenetic features of hypoxic tumour aggressiveness in localized prostate cancer

BackgroundTumor hypoxia is associated with prostate cancer (PCa) treatment resistance and poor prognosis. Pimonidazole (PIMO) is an investigational hypoxia probe used in clinical trials. A better understanding of the clinical significance and molecular alterations underpinning PIMO-labeled tumor hypoxia is needed for future clinical application. Here, we investigated the clinical significance and molecular alterations underpinning PIMO-labeled tumor hypoxia in patients with localized PCa, in order to apply PIMO as a prognostic tool and to identify potential biomarkers for future clinical translation.MethodsA total of 39 patients with localized PCa were recruited and administered oral PIMO before undergoing radical prostatectomy (RadP). Immunohistochemical staining for PIMO was performed on 37 prostatectomy specimens with staining patterns evaluated and clinical association analyzed. Whole genome bisulfite sequencing was performed using laser-capture of microdissected specimen sections comparing PIMO positive and negative tumor areas. A hypoxia related methylation molecular signature was generated by integrating the differentially methylated regions with previously established RNA-seq datasets.ResultsThree PIMO staining patterns were distinguished: diffuse, focal, and comedo-like. The comedo-like staining pattern was more commonly associated with adverse pathology. PIMO-defined hypoxia intensity was positively correlated with advanced pathologic stage, tumor invasion, and cribriform and intraductal carcinoma morphology. The generated DNA methylation signature was found to be a robust hypoxia biomarker, which could risk-stratify PCa patients across multiple clinical datasets, as well as be applicable in other cancer types.ConclusionsOral PIMO unveiled clinicopathologic features of disease aggressiveness in localized PCa. The generated DNA methylation signature is a novel and robust hypoxia biomarker that has the potential for future clinical translation.

QOL-53. EXPLORING HEADACHES IN PEDIATRIC NEURO-ONCOLOGY PATIENTS: A SINGLE INSTITUTION RETROSPECTIVE CHART REVIEW

Abstract BACKGROUND Despite the high prevalence of headaches in pediatric patients with brain tumors, very little research has been done to characterize their traits and to assess current management practices. Effective and efficient treatment of these headaches is critical to the optimization of brain tumor survivors’ quality of life. Foundational knowledge of any clinical associations likely would be beneficial to develop rational management strategies. METHODS A retrospective single-institution chart review of pediatric patients seen in the Children’s Hospital Colorado (CHCO) Neuro-oncology clinic from 1/1/22-12/31/22 is underway. Information is being collected via manual chart review including basic demographic information, oncologic diagnosis and tumor location, surgical interventions, and tumor-directed treatments. Headache characteristics, including timing of onset, associated symptoms, severity and frequency, referral to CHCO Neurology Headache Clinic and any headache therapies attempted will be sought. Additional information will include the number of emergency department visits and unplanned MRIs obtained as part of headache management. RESULTS 384 patients (53% male; median age 12 years, range 2-24 years) received care in the CHCO Neuro-oncology clinic in 2022. The majority of these patients were Caucasian/Non-Hispanic (61.7%), followed by Caucasian/Hispanic (13.8%) and African American/Non-Hispanic (4.2%). In this cohort, the preferred language for 93% was English and for 6% was Spanish. The majority (55%) of patients had a low-grade glioma/ glioneuronal tumor as their oncologic diagnosis. Patients with referrals to CHCO Headache clinic made up 13% of this cohort. Data collection and analysis are ongoing. CONCLUSIONS This data set will help to characterize the prevalence and features of headaches in pediatric patients with CNS tumors. This information will serve as the foundation for planned prospective studies that will collect more comprehensive and consistent data related to headaches in the pediatric neuro-oncology population and to formalize processes that will identify appropriate patients for referral to specialized headache providers.

Role of SYT11 in human pan-cancer using comprehensive approaches

BackgroundSynaptotagmin 11 (SYT11) plays a pivotal role in neuronal vesicular trafficking and exocytosis. However, no independent prognostic studies have focused on various cancers. In this study, we aimed to summarize the clinical significance and molecular landscape of SYT11 in various tumor types.MethodsUsing several available public databases, we investigated abnormal SYT11 expression in different tumor types and its potential clinical association with prognosis, methylation profiling, immune infiltration, gene enrichment analysis, and protein–protein interaction analysis, and identified common pathways.ResultsTCGA and Genotype-Tissue Expression (GTEx) showed that SYT11 was widely expressed across tumor and corresponding normal tissues. Survival analysis showed that SYT11 expression correlated with the prognosis of seven cancer types. Additionally, SYT11 mRNA expression was not affected by promoter methylation, but regulated by certain miRNAs and associated with cancer patient prognosis. In vitro experiments further verified a negative correlation between the expression of SYT11 and miR-19a-3p in human colorectal, lung, and renal cancer cell lines. Moreover, aberrant SYT11 expression was significantly associated with immune infiltration. Pathway enrichment analysis revealed that the biological and molecular processes of SYT11 were related to clathrin-mediated endocytosis, Rho GTPase signaling, and cell motility-related functions.ConclusionsOur results provide a clear understanding of the role of SYT11 in various cancer types and suggest that SYT11 may be of prognostic and clinical significance.