Evaluation Of Disease Status Research Articles

Proteomic discovery of non-invasive biomarkers of localized prostate cancer using mass spectrometry.

Prostate cancer is the second most frequently diagnosed non-skin cancer in men worldwide. Patient outcomes are remarkably heterogeneous and the best existing clinical prognostic tools such as International Society of Urological Pathology Grade Group, pretreatment serum PSA concentration and T-category, do not accurately predict disease outcome for individual patients. Thus, patients newly diagnosed with prostate cancer are often overtreated or undertreated, reducing quality of life and increasing disease-specific mortality. Biomarkers that can improve the risk stratification of these patients are, therefore, urgently needed. The ideal biomarker in this setting will be non-invasive and affordable, enabling longitudinal evaluation of disease status. Prostatic secretions, urine and blood can be sources of biomarker discovery, validation and clinical implementation, and mass spectrometry can be used to detect and quantify proteins in these fluids. Protein biomarkers currently in use for diagnosis, prognosis and relapse-monitoring of localized prostate cancer in fluids remain centred around PSA and its variants, and opportunities exist for clinically validating novel and complimentary candidate protein biomarkers and deploying them into the clinic.

O52 Plasma circulating cell-free messenger RNA as a potential biomarker of melanoma

Abstract Introduction Blood-borne cell-free nucleic acids are increasingly emerging as significant non-invasive adjuncts to current methods of disease status evaluation in cancer patients. In this study, we sought to examine whether significant differences exist in the plasma transcriptomic profile of advanced melanoma patients with a high disease burden compared to patients with therapeutic response. Method Plasma circulating cell-free messenger ribonucleic acid (ccfmRNA) was extracted from twenty patients with stage IV melanoma receiving immunotherapy. Pathway focused gene expression analysis was performed. Patients were assessed with paired blood sample collection and CT scan assessments at baseline and at 3 months follow up. Response Evaluation Criteria in Solid Tumours (RECIST 1.1) was used for tumour burden estimation. Result In stage IV melanoma patients, CCL5, GZMB and MYD88 genes were significantly over-expressed (P < 0.05 versus healthy controls). In patients with high disease burden or progressive disease, CCL18, CCR1, CCR4, CD274, CSF2, and GBP1 genes were significantly over-expressed (P < 0.05 versus patients with therapeutic response). Finally, in stage IV melanoma patients with brain metastases, CCL18, CCR1, CCR4, CD274, CSF2, EGF, GBP1, and PTGS2 genes were significantly over-expressed (P < 0.05, versus patients without brain metastasis). Conclusion Significant differences were observed in the plasma transcriptomic profile between the various melanoma patient groups, and we postulate that these differences may be exploited to identify novel therapeutic targets or biomarkers relevant to melanoma. CCL4 and CCL5 are prognostic in melanoma, both genes had significantly higher expressions in low disease burden patients compared to patients with a high disease burden. Take-home Message CCL4 and CCL5 ccfmRNA transcripts are prognostic in melanoma. High expression of both genes is favourable in melanoma patients.

Five-Year Survival Results: Frontline Brentuximab Vedotin in Combination with CHP in Patients with CD30-Expressing Peripheral T-Cell Lymphomas

Five-Year Survival Results: Frontline Brentuximab Vedotin in Combination with CHP in Patients with CD30-Expressing Peripheral T-Cell Lymphomas

Outcomes after high-dose radiation in the management of neuroendocrine neoplasms.

BackgroundNeuroendocrine neoplasms (NENs) comprise a rare and heterogenous group of cancers, for which the role of radiation therapy continues to evolve. The purpose of this study is to analyze oncologic outcomes after the use of high-dose radiation in management of NENs at a tertiary hospital.Materials and methodsWe performed a retrospective review of patients who received high-dose radiation with intent to cure or provide durable local control (defined as biologically effective dose (BED) ≥40, α/β = 10) for a localized or metastatic NEN from 2006 to 2019. Evaluation of disease status after radiation was performed according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria when possible. Patients were grouped by differentiation (well-differentiated (WD) or poorly-differentiated (PD)) and stage (localized/locally advanced disease (L) or metastatic (M)) in analysis of probabilities of progression after radiation.Results45 patients completed a radiation course with BED ≥40 for a NEN (median BED 72). With a median follow-up of 24 months after radiation, the 2-year actuarial rates of local relapse-free survival, new metastasis-free survival, progression-free survival, and overall survival after radiation were 98%, 45%, 41%, and 69%, respectively. 25 patients (56%) developed new metastases after completion of radiation, including 33% (n = 3) of patients with WD-L disease, 44% (n = 8) of WD-M, 77% (n = 10) of PD-L, and 80% (n = 4) of PD-M, with progressively shorter median times to progression (26, 9, 8, and 3 months, respectively; p = 0.093). Of the 25 patients evaluable by RECIST, 68% (n = 17) achieved either a complete or partial best response in the irradiated lesion.ConclusionsThese data suggest that focal, high-dose radiation has a role in the management of selected patients with NENs. Local failure is rare in patients with both well-differentiated and poorly-differentiated disease, although the predominant pattern of failure remains development of new metastases.

Plasma circulating cell free messenger RNA as a potential biomarker of melanoma

Background Blood borne cell free nucleic acids are increasingly emerging as significant non-invasive adjuncts to current methods of disease status evaluation in cancer patients. In this study, we sought to examine whether significant differences exist in the plasma transcriptomic profile of advanced melanoma patients with a high disease burden compared to patients with a low disease burden or therapeutic response. Methods Pathway focussed gene expression analysis was performed using cDNA derived from the plasma circulating cell free messenger ribonucleic acid (ccfmRNA) samples of twenty-two patients with advanced melanoma. Patients were assessed with paired blood sample collection and CT scan assessments at baseline and at 3 months follow up. Results We identified several genes which were significantly over-expressed in patients with a low disease burden or therapeutic response; BCL2L1, CXCL9, IDO1, IL13, MIF, MYD88 and TLR4 (p ≤ 0.001, versus high disease burden). There was an increase in the magnitude of fold change (2^ (-dd CT)) of BCL2L1 (p = 0.031), CCL4 (p = 0.001), CCL5 (p = 0.043), CXCL9 (p = 0.012), GZMB (p = 0.023) and TNFSF10 (p = 0.039) genes in patients with therapeutic response at 3 months follow up assessment relative to baseline assessment. Moreover, in stage IV melanoma patients with brain metastases, CCL18, CCR1, CCR4, CD274, CSF2, EGF, and PTGS2 genes were significantly over-expressed (p < 0.001, versus patients without melanoma brain metastasis). Conclusion Significant differences were observed in the plasma transcriptomic profile between the various melanoma patient groups, and we postulate that these differences may be exploited to identify novel therapeutic targets or biomarkers relevant to melanoma.

Machine Learning Classifiers for ADHD and Comorbid Disorders

Machine learning (ML) have been applied to brain MRI data to derive automated diagnosis, evaluation of disease status and treatment effects. However, the accuracies and sensitivities of classification models for psychiatric disorders are usually low and not yet suitable for clinical use, likely due to inadequate sample sizes. Secondly, brains structures form a complex and interconnect network, in which different disorders often selectively affect different parts of the network. Identification and extraction of these informative structures may help to improve the ML prediction performance.

Pediatric radiologic manifestations of COVID-19

PurposeWhile full description of pediatric COVID-19 manifestations is evolving, children appear to present less frequently, and often display a less severe disease phenotype. There is correspondingly less data regarding pediatric radiologic findings. To describe the imaging findings of pediatric COVID-19, we evaluated the radiologic imaging of the initial patient cohort identified at our institution. MethodsIn this IRB approved study, all patients at our institution aged 0–21 with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on PCR or immunoglobulin testing were identified. Imaging was reviewed by the co-authors and presence of abnormalities determined by consensus. Pre-existing comorbidities and alternative diagnoses were recorded. Rates of each finding were calculated. Findings were compared to published data following review of the available literature. ResultsOut of 130 Covid-19 positive patients, 24 patients underwent imaging, including 21 chest radiographs and 4 chest CT scans. Chest x-rays were normal in 33%. Patchy or streaky opacities were the most common radiographic abnormality, each seen in 38% of patients. CT findings included ill-defined or geographic ground glass opacities, dense opacities, septal thickening and crazy paving, and small pleural effusions. Results are similar to those reported in adults. Multiple COVID-19 positive children presented for symptoms due to an additional acute illness, including appendicitis and urinary infection. ConclusionsRadiologic findings of COVID-19 in pediatric patients range from normal to severe ARDS type appearance. During this ongoing pandemic, these radiographic signs can be useful for the evaluation of disease status and guiding care, particularly in those with comorbidities. PrecisRadiologic findings of COVID-19 in pediatric patients are similar to those seen in adults, and may range from normal to severe ARDS type appearance.

Predicting Non-Alcoholic Fatty Liver Disease Progression and Immune Deregulations by Specific Gene Expression Patterns.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide with rising rates in parallel to obesity, type 2 diabetes, and metabolic syndrome. NAFLD includes pathologies ranging from simple steatosis (NAFL) to non-alcoholic steatohepatitis and cirrhosis (NASH), which may eventually develop into hepatocellular carcinoma (HCC). Mechanically, lipids accumulation and insulin resistance act as the first hit, inflammation and fibrosis serve as the second hit. Currently, the diagnosis of NAFLD mainly depends on pathology examination and medical imaging, whereas proper gene signature classifiers are necessary for the evaluation of disease status. Here, we developed three signature classifiers to distinguish different NAFLD disease states (NAFL and NASH). Moreover, we found that B cells, DCs, and MAIT cells are key deregulated immune cells in NAFLD, which are associated with NAFLD and NAFLD-HCC progression. Meanwhile, AKR1B10 and SPP1 are closely related to the above three immune cell infiltrations and immunosuppressive cytokines expressions in NAFLD and NAFLD-HCC. Subsequently, we screened out AKR1B10 and SPP1 sensitive molecules TGX-221, which may provide a possible therapy for NAFLD and NAFLD-HCC.

ALT Flare Predicts Hepatocellular Carcinoma Among Antiviral Treated Patients With Chronic Hepatitis B: A Cross-Country Cohort Study.

ObjectivesAlanine aminotransferase (ALT) level is one of the crucial indexes to evaluate disease status for chronic hepatitis B (CHB) patients. However, whether the ALT level after nucleos(t)ide analog (NA) treatment is associated with hepatocellular carcinoma (HCC) development remains unclear.Materials and MethodsWe evaluated the association between ALT level and HCC occurrence in NA-treated patients and investigated the predictive value of ALT flare for HCC. The associations between ALT level and HCC were analyzed by logistic regression and Cox proportional hazards models.ResultsThere were 21,223 CHB patients at Ruijin Hospital of China and 16,737 CHB patients in the Optum electronic health records (EHR) in the United States (US) treated with NAs between 2010 and 2018. Among them, 8,152 and 4,893 patients who achieved a normal ALT value were included in the study cohorts, respectively. A significant positive dose-dependent correlation between the peak ALT level and HCC was identified in both cohorts. Within the China cohort, ALT flare was significantly associated with increased risks of HCC compared to normal ALT (HR 2.55, 95%CI 1.45–4.50). Stronger increased risks associated with ALT flare were observed in the US cohort (HR 7.62, 95%CI 4.85–11.98).ConclusionsALT flare is a strong predictor for HCC occurrence in the CHB patients treated with NAs. Elevation of ALT, especially ALT flare warrants close monitoring for early HCC detection.

A Comparison of Beclomethasone Aqueous Spray and Aerosol Delivery System in Nasal Polyps: A Randomized Control Trial.

Background:Considering the effect of beclomethasone on allergic rhinitis or nasal polyps, it has been attempted to find the best method of using this drug to have the maximum effect and increase the patients' satisfaction. Therefore, the aim of this study was to compare the efficacy of beclomethasone aerosol and aqueous nasal sprays in the patients with nasal polyps.Materials and Methods:This double-blind randomized clinical trial was conducted on 60 patients with nasal polyps. The patients were divided into two groups. The first group (beclomethasone dipropionate aqueous [BD-AQ] group) was treated with daily two puffs of beclomethasone aqueous nasal spray 50 μg in each nostril, and the second group (beclomethasone dipropionate aerosol [BD-A] group) was treated with two puffs of aerosol beclomethasone 50 μg in each nostril daily for 6 months. At the beginning of the study, the sino-nasal outcome test-22 (SNOT-22) and Lund-Mackay scores were recorded after the evaluation of disease status and the severity of symptoms.Results:The results of this study demonstrated that the mean changes in Lund-Mackay and SNOT-22 scores (83 ± 6.30 and 4.25 ± 31.60, respectively) in the BD-A group were significantly higher than the BD-AQ group (2.01 ± 3.87and 9.83 ± 24.13, respectively) (P < 0.05), but there was no significant difference in the patients' satisfaction between the two groups (P > 0.05).Conclusion:According to the results of this study, patients with nasal polyps showed a significant improvement following both the interventions, but the disease severity in the BD-A group was significantly higher than the BD-AQ group based on the mean values of Lund-Mackay score.

Applications of Bioelectrical Impedance Analysis in Diagnosis of Diseases: A Systematic Review

Introduction: Bioelectrical Impedance Analysis (BIA) is a safe, non-invasive, painless, portable, and inexpensive technology that has the prospect to provide information related to the dynamic performance of the human body. Body Composition (BC) assessment is widely accepted as a clinical method to diagnose and evaluate disease status. Aim: To predict and validate the applicability of BIA in diagnosis of diseases such as Chronic Kidney Disease (CKD), Chronic Obstructive Pulmonary Disease (COPD), Heart Failure (HF), Pregnancy and Spinal Cord Injury (SCI). Materials and Methods: A systematic clinical review was conducted following the PRISMA guidelines {PubMed, The Cochrane Archive, Web of Research, Medline, and SPORTDiscus with complete text (EBSCO)}. A literature review was carried out randomly, from 2000 to 2018, published in English; the keyword combinations were evaluated using Boolean operators “OR” and “AND” for BIA, CKD, COPD, HF, Pregnancy, SCI. Results: A total of 1156 search terms, 1139 citations were excluded, and 17 potentially qualifying articles were shortlisted. Hence, as per the inclusion criteria, three articles on COPD, three articles on CKD, three articles on pregnancy, four articles on HF, and four SCI articles were shortlisted. Conclusion: The calculated BIA parameters showed that the patient’s actual health could be analysed quickly to monitor the disease progression and provide significant advances in developing therapies for the diseases. However, this paper recommends further study on BIA to improve a clinical assessment of BC.

Validation of a breath-holding test as a screening test for exercise-induced hypoxemia in chronic respiratory diseases.

The detection of exercise-induced hypoxemia is important for evaluating disease status in patients with chronic respiratory diseases. The 6-min walk test (6MWT) is useful for detecting exercise-induced hypoxemia. This pilot study aimed to validate the breath-holding test (BHT) as a screening for exercise-induced hypoxemia and compare its utility with that of the 6MWT in patients with chronic respiratory diseases. Fifty-nine patients with chronic respiratory diseases underwent BHTs lasting 10, 15, and 20 s. Percutaneous oxygen saturation (SpO2), pulse rate, and severity of dyspnoea were measured. The participants also underwent a 6MWT, a pulmonary function test, and analysis of arterial blood gas at rest. Multivariate linear regression analysis was performed to identify significant predictors of desaturation in the 6MWT. The minimum SpO2 during the BHT (all durations) and 6MWT were significantly correlated. Receiver operating characteristic analysis revealed the optimal cut-off for predicting SpO2 < 90% during the 6MWT as a minimum SpO2 ≤ 94% during the 15-s BHT. Perceived dyspnoea and maximum pulse rate were significantly lower during the 15-s BHT than during the 6MWT. In the multivariate linear regression analysis, the minimum SpO2 during the 15-s BHT (β, 0.565, p < 0.001) and %DLco (β, 0.255, p < 0.028) were independent predictors of desaturation in the 6MWT. The minimum SpO2 during the 15-s BHT may be a useful measure for screening for exercise-induced hypoxemia in patients with chronic respiratory diseases. The BHT is easier to perform, more readily available, and better tolerated than the 6MWT.

Does Including Pain, Fatigue, and Physical Function When Assessing Patients with Early Rheumatoid Arthritis Provide a Comprehensive Picture of Disease Burden?

To explore the possibility of integrating patient-important outcomes like pain, fatigue, and physical function into the evaluation of disease status in early rheumatoid arthritis (ERA) without compromising correct disease activity measurement. Patients from the 2-year Care in Early Rheumatoid Arthritis (CareRA) trial were included. Pain and fatigue (visual analog scales), Health Assessment Questionnaire (HAQ), standard components of disease activity [swollen/tender joint counts (SJC/TJC), C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR), physician (PhGH) and patient (PaGH) global health] were recorded at every visit (n = 10). Pearson correlation and exploratory factor analyses (EFA), using multiple imputation (15×) and outputation (1000×), were performed per timepoint and overall, on standard components of disease activity scores with and without pain, fatigue, and HAQ. Each of the 15,000 datasets was analyzed using EFA with principal component extraction and oblimin rotation to determine which variables belong together. We included 379 patients. EFA on standard composite score components extracted 2 factors with no substantial cross-loadings. Still, pain (0.83), fatigue (0.65), and HAQ (0.59) were strongly correlated with PaGH. When rerunning the EFA with the inclusion of pain, fatigue, and HAQ, the 2-factor model had substantial cross-loadings between factors. However, a 3-factor model was optimal, with Factor 1: patient assessment, Factor 2: clinical assessment (PhGH, SJC, and TJC), and Factor 3: laboratory assessment (ESR/CRP). PaGH, pain, fatigue, and physical function represent a separate aspect of the disease burden of patients with ERA, which could be further explored as a target for care apart from disease activity. [ClinicalTrials.gov: NCT01172639].

Correlation of urticaria activity score in chronic spontaneous urticaria with serum C-reactive protein level and neutrophil/lymphocyte ratio.

Chronic spontaneous urticaria (CSU) lacks a specific trigger. The urticaria activity score (UAS) is used to evaluate disease status. Some studies have reported elevated serum levels of high-sensitivity C-reactive protein (hsCRP) in CSU patients, which is correlated with disease severity. The neutrophil/lymphocyte (N/L) ratio is a significant indicator of systemic inflammation. We investigated the potential correlation between serum levels of hsCRP and N/L ratio, as well as urticaria activity, in CSU patients. We included 52 CSU patients treated at the Dermatology Polyclinic of Beysehir State Hospital between August and October 2020, and 50 controls. The 7-day UAS were graded mild, moderate, or intense. We measured N/L ratios, erythrocyte sedimentation rates (ESRs), and the levels of hsCRP, T4, and thyroid-stimulating hormone (TSH) in each group. The anti-thyroglobulin (anti-TG) and anti-microsomal antibody (anti-TPO) levels of CSU patients were also assayed. There were no significant differences in hsCRP, T4, or TSH levels between the groups; however, both the ESR and N/L ratio were significantly higher in CSU patients hsCRP (P = .96), T4 (P = .07), TSH (P = .67), ESR (P < .001), N/L(P < .001). No correlation was evident between the UAS day 7 (UAS7) score and the hsCRP level or the N/L ratio (P = .528 and P = .387). Of all the CSU patients, 19.2% tested positive for anti-TPO and 9.6% were positive for anti-TG; these data were not correlated with the UAS7 (P = 1 and P = .637). Inflammation plays a role in CSU. Although we did not find a correlation between the UAS and either the hsCRP level or the N/L ratio, the ESR and N/L ratio were higher in CSU patients than in controls.

To Study The Role Of Pre-treatment MicroRNA Expression As A Predictor Of Response To Chemoradiation In Locally Advanced Carcinoma Cervix

Cervical cancer is the fourth most common cancer worldwide. External beam radiotherapy with concurrent cisplatin followed by brachytherapy is considered standard of care in locally advanced carcinoma cervix, with 50% of patients presenting with recurrence or persistent disease. At present there is no prognostic factor to predict the outcome of disease in locally advanced carcinoma cervix patients treated with standard therapy. MicroRNAs(miRNAs)are small, single stranded noncoding RNA constituting 18-22 nucleotides. It has been shown that miRNAs are differentially expressed (upregulated or downregulated) in many cancer cells. Expression of miRNAs can be used as molecular biomarkers to predict clinical response in locally advanced carcinoma cervix patients. In an observational study, we enrolled 32 patients of locally advanced carcinoma cervix (Stage IB- IVA) after pathological confirmation of biopsy sample from 2017-2018. Expression of six microRNA (miRNA-9 5p, miRNA-31 3p, miRNA-100 5p, miRNA-125a 5p, miRNA-125b-5p, miRNA–200a 5p) in formalin fixed paraffin embedded (FFPE) biopsied tissue were analyzed by real time quantitative reverse transcriptase polymerase chain reaction (RT qPCR). Pre-treatment evaluation of disease status was done with clinical examination and MRI pelvis imaging. All patients received external beam radiotherapy with concurrent chemoradiotherapy followed by brachytherapy as standard treatment. Patients were evaluated for clinical response after 3 months of completion of treatment, with clinical examination and MRI pelvis scan using RECIST 1.1 criteria. Responses were classified as complete response (CR) as disappearance of all disease in response to treatment and Non-response (NR) as patients with partial response, stable or progressive disease. Results were statistically analyzed using Mann Whiney U test to examine significant difference between expression of microRNA between patients with complete clinical response (CR) and those with non-response (NR). Out of total 32 patients, 24 patients (75%) had Complete Response and 8 patients (25%) had Non-Response to standard therapy. Out of six miRNAs, expression of miRNA-100 5p was upregulated in complete responders (CR) and downregulated in Nonresponders (NR), which showed a trend towards statistical significance (p value = 0.05). Other microRNAs (miRNA-9 5p, miRNA-31 3p, miRNA-125a 5p, miRNA-125b 5p, miRNA–200a 5p) showed differential expression in complete responders compared to non-responders but their expression did not reach statistical significance level (p value > 0.05). miRNA-100 5p can serve as a potential molecular biomarker in predicting clinical response to chemoradiation in locally advanced Carcinoma cervix patients. Its role should be further investigated in larger study population.

A Novel Three-lncRNA Signature Predicts the Overall Survival of HNSCC Patients.

A number of long non-coding RNAs (lncRNAs) have been found to be involved in tumor progression and associated with disease prognoses in various types of cancer. Our study identified a novel three-lncRNA signature to predict survival of head and neck squamous cell caner (HNSCC) patients. We utilized The Cancer Genome Atlas (TCGA) cohort to screen out overall survival (OS)-associated lncRNAs in HNSCC and further developed a model to identify a lncRNA signature for evaluating disease status and prognosis. The lncRNA signature was then validated in HNSCC patients from our Fudan University Shanghai Cancer Center (FUSCC) cohort. LINC02434, AL139327.2, and AC126175.1 were identified by multivariable Cox regression analyses of independent risk factors for deceased status. We built a risk score model based on the three-lncRNA signature using coefficient of multivariable Cox regression and expression value of the three lncRNAs. The high-risk signature score was significantly associated with decreased OS in both the TCGA cohort and the FUSCC cohort. The high-risk group had worse overall survival than the low-risk group in TCGA cohort. To further validate the robustness of three-lncRNA signature risk score model developed in the TCGA dataset, the performance of risk score also evaluated in our institute FUSCC cohort. Additionally, the signature score showed a positive correlation with aggressive outcomes of HNSCC, such as III/IV stage, TP53 mutation, and PI3KCA mutation. The gene set enrichment analysis indicates that the risk score is associated with cancer metastasis-related pathways. Several cancer-related pathways, such as epithelial mesenchymal transition, TNFα signaling via NF-κB, MYC targets, and angiogenesis. The three-lncRNA signature could provide a novel prediction insight into the prognosis of HNSCC patients. The three-lncRNA signature was identified as a predictor of poor prognoses in HNSCC, which may serve as a potential therapeutic target.

Abstract 1652: Tumor-specific PET imaging with an 18F-labeled tryptophan analogue in a transgenic medulloblastoma mouse model

Abstract In vivo positron emission tomography (PET) imaging is a key modality to evaluate disease status of brain tumors. In recent years, tremendous efforts have been made in developing PET imaging methods for pediatric brain tumors. Carbon-11 labelled tryptophan derivatives are feasible as PET imaging probes in brain tumor patients with activation of the kynurenine pathway, but the short half-life of carbon-11 limits its application. Using a transgenic mouse model for the sonic hedgehog (Shh) subgroup of medulloblastoma, here we evaluated the potential of the newly developed 1-(2-[18F]fluoroethyl)-L-tryptophan (1-L-[18F]FETrp) as a PET imaging probe for this common malignant pediatric brain tumor. 1-L-[18F]FETrp was synthesized on a PETCHEM automatic synthesizer with good chemical and radiochemical purities and enantiomeric excess values. Imaging was performed in tumor-bearing Smo/Smo medulloblastoma mice using a Perkin-Elmer G4 PET-X-Ray scanner. Medulloblastoma tumors showed significant and specific accumulation of 1-L-[18F]FETrp. 1-L-[18F]FETrp also showed significantly higher tumor uptake than its D-enantiomer 1-D-[18F]FETrp. The uptake of 1-L-[18F]FETrp in normal brain tissue was low, suggesting that 1-L-[18F]FETrp may prove a valuable PET imaging probe for the Shh subgroup of medulloblastoma and possibly other pediatric and adult brain tumors. Citation Format: Xuyi Yue, Yangchun Xin, Hua Li, Zhiqin Li, Hancheng Cai, Sigrid A. Langhans. Tumor-specific PET imaging with an 18F-labeled tryptophan analogue in a transgenic medulloblastoma mouse model [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1652.

Correlative study of disease activity in Langerhans cell histiocytosis.

e19540 Background: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia that primarily affects younger children, most often involving bone, skin, lung, lymph nodes, or liver. Current treatment for LCH includes chemotherapy and biologically targeted therapies. Given its clinical heterogeneity and low prevalence, decision-making regarding intervention relies on subjective evaluation of disease status, which is often dependent on provider experience. Thus, there is a need to identify biomarkers for disease recurrence and activity in patients with LCH. Methods: We conducted a retrospective cohort study including pediatric LCH patients (n = 48) ≤21 years of age with biopsy-proven diagnosis of LCH and ≥1 year of follow-up after diagnosis. Data regarding demographics, symptom history, organ system involvement, and laboratory values at different time points were extracted from the from patient medical records and entered into a REDCap Database. The primary outcome was recurrence status as measured by the end of the study period. Data were analyzed using Stata statistical analysis software. Results: In our cohort, the sample was 64.6% Male and 35.4% Female with a median age of 29 months at diagnosis. 68.1% of patients had single organ involvement while 31.9% exhibited multi-system involvement. 70.8% of our cohort received treatment with chemotherapy with an average initial treatment duration of 12.1 months. 27.1% of the cohort experienced recurrence by the time of chart review. Logistic regression of the demographic factors and lab values at diagnosis revealed a statistically significant association between multi-system involvement (OR: 3.94, p = 0.04), moderate or high central nervous system risk assessment (OR: 7.67, p = 0.03; OR: 5.75, p = 0.03) and likelihood of recurrence. Additionally, logistic regression analysis revealed that alkaline phosphatase level at the time of diagnosis was associated with a slightly decreased likelihood of recurrence (OR: 0.987, p = 0.02). Conclusions: These results reveal that in addition to the traditionally utilized inflammatory markers (Erythrocyte Sedimentation Rate, White Blood Cell and Platelet Count), Alkaline Phosphatase could be used as a predictor of disease activity for patients with LCH, especially for those with bone involvement. Moving forward, an increased sample size might reveal other correlative biomarkers that can predict disease activity, helping to more precisely manage LCH.

Improved Classification Performance With Autoencoder-Based Feature Extraction Using Cross-Disorder Datasets

Machine learning (ML) have been applied to brain MRI data to derive automated diagnosis, evaluation of disease status and treatment effects. However, the accuracies and sensitivities of classification models for psychiatric disorders are usually low and not yet suitable for clinical use, likely due to inadequate sample sizes. Secondly, brains structures form a complex and interconnect network, in which different disorders often selectively affect different parts of the network. Identification and extraction of these informative structures may help to improve the ML prediction performance.

Resistin in metabolism, inflammation, and disease.

Resistin is a small secretory protein that has a pleiotropic role in rodents and humans. Both rodent resistin and human resistin have an extremely stable and high-order multimeric structure. Moreover, there is significant variation in the source of secretion and the diversity of functions of resistin. Mouse resistin resists insulin action and contributes to type 2 diabetes mellitus, while human resistin plays a role in inflammation and also functions as a small accessory chaperone. Currently, active research in the area identified a significant role for resistin in stress biology and as a biomarker in diagnostics to evaluate disease status and treatment outcome. This review summarizes recent developments within resistin biology including their association with obesity, inflammation, stress response mechanisms, and its role in clinical diagnostics.