Clinical Stage Of Disease Research Articles

Bovine Immunity and Vitamin D3: An Emerging Association in Johne's Disease.

Mycobacterium avium subspecies paratuberculosis (MAP) is an environmentally hardy pathogen of ruminants that plagues the dairy industry. Hallmark clinical symptoms include granulomatous enteritis, watery diarrhea, and significant loss of body condition. Transition from subclinical to clinical infection is a dynamic process led by MAP which resides in host macrophages. Clinical stage disease is accompanied by dysfunctional immune responses and a reduction in circulating vitamin D3. The immunomodulatory role of vitamin D3 in infectious disease has been well established in humans, particularly in Mycobacterium tuberculosis infection. However, significant species differences exist between the immune system of humans and bovines, including effects induced by vitamin D3. This fact highlights the need for continued study of the relationship between vitamin D3 and bovine immunity, especially during different stages of paratuberculosis.

A novel chest CT severity score in COVID-19 and its correlation with severity and prognosis of the lung disease: A retrospective cohort study.

BackgroundHRCT chest has a high sensitivity in the diagnosis of patients with COVID-19 infection. Through our study, we intend to evaluate the diagnostic accuracy and inter-reader variability of a semi-quantitative CT severity score, a novel parameter designed for risk stratification and prognostication of COVID-19 pneumonia with clinical staging of disease.MethodsIt was a single-center retrospective analysis performed on an original cohort of 4180 symptomatic patients with the suspicion of SARS-CoV-2 interstitial pneumonia. Out of 4180, a total of 4004 patients with COVID-19 were confirmed by an RT-PCR. We used an HRCT chest severity score (CT-SS) to evaluate the COVID-19 disease burden on the initial scan obtained at admission. The data were analyzed with IBM SPSS Statistics Version 22.0 Release 2013.ResultsOur study subjects demonstrated the most common clinical features fever, cough, dyspnea, and body aches. Raised CRP levels (CRP >0.5 mg/dL) were found in 81.86% and increased D-dimer levels (>500 ng/mL) were found in 92.3% of patients. The most common radiological findings of the disease included ground-glass opacities, observed in 98.8%. Our study has a sensitivity of 89.2%, a specificity of 94.8%, a positive predictive value (PPV) of 90.6%, and a negative predictive value (NPV) of 94%.ConclusionAs per our findings, this novel CT scoring system might aid in the risk stratification and the short-term prognostication of patients suffering from COVID-19 pneumonia. This will eventually help in curtailing the extensive burden on the healthcare system amid the current pandemic.

Combinatorial treatment of brain samples from sheep with scrapie using sodium percarbonate, sodium dodecyl sulfate, and proteinase K increases survival time in inoculated susceptible sheep

The agent of scrapie is resistant to most chemical and physical methods of inactivation. Prions bind to soils, metals, and various materials and persist in the environment confounding the control of prion diseases. Most methods of prion inactivation require severe conditions such as prolong exposure to sodium hypochlorite or autoclaving, which may not be suitable for field conditions. We evaluated the efficacy of a combinatorial approach to inactivation of US scrapie strain x124 under the mild conditions of treating scrapie-affected brain homogenate with sodium percarbonate (SPC), sodium dodecyl sulfate (SDS), or in combination followed by proteinase K (PK) digestion at room temperature. Western blot analysis of treated brain homogenate demonstrates partial reduction in PrPSc immunoreactivity. Genetically susceptible VRQ/ARQ Suffolk sheep were oronasally inoculated with 1 g of SPC (n = 1), SDS (n = 2), SDS + PK (n = 2), and SPC + SDS + PK (n = 4) treated brain homogenate. Sheep were assessed daily for clinical signs, euthanized at the development of clinical disease, and tissues were assessed for accumulation of PrPSc. Scrapie status in all sheep was determined by western blot, enzyme immunoassay, and immunohistochemistry. Mean incubation periods (IPs) for SPC (11.9 months, 0% survival), SDS (12.6 months, 0% survival), SDS + PK (14.0 months, 0% survival), and SPC + SDS + PK (12.5 months, 25% survival) were increased compared to positive control sheep (n = 2, 10.7 months, 0% survival) by 1.2, 1.9, 3.3, and 1.8 months, respectively. Treatment did not influence PrPSc accumulation and distribution at the clinical stage of disease. Differences in mean IPs and survival indicates partial but not complete reduction in scrapie infectivity.

Disease-Associated α-Synuclein Aggregates as Biomarkers of Parkinson Disease Clinical Stage.

Robust biomarkers that can mirror Parkinson disease (PD) are of great significance. In this study, we present a novel approach to investigate disease-associated α-synuclein (αSyn) aggregates as biomarkers of PD clinical stage. We combined both seed amplification assay (SAA) and ELISA to provide a quantitative test readout that reflects the clinical severity of patients with PD. To attain this goal, we initially explored the potential of our test using 2 sets of human brain homogenates (pilot and validation sets) and then verified it with 2 independent human CSF cohorts; discovery (62 patients with PD and 34 controls) and validation (49 patients with PD and 48 controls) cohorts. We showed that oligomers-specific ELISA robustly quantified SAA end product from patients with PD or dementia with Lewy bodies with high sensitivity and specificity scores (100%). Analysis also demonstrated that seeding activity could be detected earlier with oligomeric ELISA as the test readout rather than SAA alone. Of more importance, multiplexing the assays provided robust information about the patients' clinical disease stage. In the discovery cohort, levels of CSF-seeded αSyn oligomers correlated with the severity of the clinical symptoms of PD as measured by the Unified Parkinson Disease Rating Scale (UPDRS) motor (r = 0.58, p < 0.001) and Hoehn and Yahr (H&Y) scores (r = 0.43, p < 0.01). Similar correlations were observed in the validation cohort between the concentrations of CSF-seeded αSyn oligomers and both UPDRS motor (r = 0.50, p < 0.01) and H&Y scores (r = 0.49, p < 0.01). At 20 hours, receiver operating characteristic curves analysis yielded a sensitivity of 91.9% (95% CI 82.4%-96.5%) and a specificity of 85.3% (95% CI 69.8%-93.5%), with an area under the curve of 0.969 for CSF-seeded αSyn oligomers differentiating those with PD from controls in the discovery CSF cohort, whereas, a sensitivity of 80.7% (95% CI 69.1%-88.5%), a specificity of 76.5% (95% CI 60.0%-87.5%), and area under the curve of 0.860 were generated with thioflavin T maximum intensity of fluorescence at the same time point. We showed that combining SAA and ELISA assays is a more promising diagnostic tool than SAA alone, providing information about the disease stage by correlating with clinical measures of disease severity. This study provides Class III evidence that CSF-seeded αSyn oligomers can accurately discriminate patients with PD and normal controls and CSF-seeded αSyn oligomers levels correlate with PD severity.

Chinese guideline on the diagnosis and treatment of thyroid-associated ophthalmopathy (2022)

Thyroid-associated ophthalmopathy (TAO) is an orbital disease closely related to thyroid diseases. TAO has a prolonged course and possibility of blindness and disability. Its diagnosis and treatment can be complex with multiple disciplines involved. To improve the standardized diagnosis and treatment of TAO in China, the Oculoplastic and Orbital Disease Group of Chinese Ophthalmological Society of Chinese Medical Association and the Thyroid Group of Chinese Society of Endocrinology of Chinese Medical Association have jointly drawn up this first clinical guideline in China for TAO by complying with the principles, methods and steps of guideline formation. In this guideline, there are 24 recommendations for the major clinical problems in the diagnosis and treatment of TAO, including the clinical diagnostic criteria, disease staging and grading methods, novel treatment based on the pathogenesis, multi-disciplinary treatment, risk factor control, individualized selection of treatment such as drugs, radiation and surgery, therapeutic efficacy evaluation and critical illness management. This guideline provides instructions for clinicians to carry out relevant clinical and research work.

Metabolomic changes in lactating multiparous naturally MAP-infected Holstein-Friesian dairy cows suggest changes in mitochondrial energy pathways

Mycobacterium avium subspecies paratuberculosis (MAP) is the causative organism of Johne's Disease, a chronic intestinal infection of ruminants. Infected cows begin shedding MAP within the asymptomatic, subclinical stage of infection before clinical signs, such as weight loss, diarrhoea and reduced milk yields develop within the clinical stages of disease. Herein, we examine the milk metabolomic profiles of naturally MAP-infected Holstein-Friesian cows. The study used biobanked milk samples which were collected 73.4 ± 3.79 (early lactation) and 143 ± 3.79 (mean ± SE) (mid-lactation) days post-calving from 5 MAP-infected and 5 control multiparous cows. The milk metabolome was assessed using flow infusion electrospray high-resolution mass spectrometry (FIE-HRMS) for sensitive, non-targeted metabolite fingerprinting. Metabolite fingerprinting assessments using partial least squares discriminate analyses (PLS-DA) indicated that lactation stage was a larger source of variation than MAP status. Examining each lactation stage separately for changes associated to MAP-infection status identified 45 metabolites, 33 in early lactation and 12 in mid-lactation, but only 6 metabolites were targeted in both stages of lactation. Pathway enrichment analysis suggested that MAP affected the malate-aspartate shuffle during early lactation. Pearson's correlation analysis indicated relationships between milk lactose concentrations in mid-lactation and 6 metabolites that were tentatively linked to MAP-infection status. The targeted metabolites were suggestive of wider changes in the bioenergetic metabolism that appear to be an acceleration of the effects of progressing lactation in healthy cows. Additionally, milk lactose concentrations suggest that MAP reduces the availability of lactose derivatives.

Levels of undernutrition and associated factors among adults receiving highly active anti-retroviral therapy in health institutions in Bench Maji Zone, Southwest Ethiopia in 2018.

BackgroundNutritional issues are common in people with Human Immune Virus (HIV). At some point, almost everyone living with HIV faces challenges in maintaining good nutrition. There is insufficient evidence-based information on undernutrition in adults living with HIV on Highly Active Anti-Retroviral Therapy.ObjectiveTo assess the magnitude of undernutrition and associated factors among patients receiving Highly Active Anti-Retroviral Therapy in health facilities in the Bench Maji Zone, southwest Ethiopia in 2018.MethodsA facility-based cross-sectional study design was employed from 1 May to 30 June 2018 on 1,007 study subjects and the participants were selected by using a consecutive sampling technique. Five health facilities were selected through a simple random sampling technique. Data were entered into Epi Data Statistical software version 3.1 and analyzed using Statistical Package for Social Sciences (SPSS) software version 21.0. Logistic regression analysis was used to identify factors associated with undernutrition in adults receiving ART. Odds ratios with 95 % confidence intervals were used to examine associations between dependent and independent variables.ResultOf the total 1,007 study subjects, 961 participated in the study. More than half of the participants were female (61.2%), 57.2% were married and 42.9% were in the 30–39 years age group. In this study, the level of undernutrition among patients on antiretroviral therapy was 16%. Age ≥50 [AOR 2.5, 95% CI (1.1–5.6)], being single [AOR 2.2, 95% CI (1.4–3.7)], developing gastrointestinal symptoms [AOR 2.6, 95% CI (1.5–4.4)] and in WHO-defined clinical stages III and IV of HIV/AIDS [AOR 2.8, 95% CI (1.3–6.0)] were found to have a statistically significant association with undernutrition.ConclusionSignificant numbers of people on highly active antiretroviral therapy in the study area were undernourished. This demonstrated that HIV/AIDs and its treatment directly or indirectly impacted the nutritional status of the patients, who need a critical follow-up from health workers. Age, marital status, progressing to WHO-defined clinical stage of disease, and development of gastrointestinal symptoms were identified as factors that contribute to undernutrition among patients on highly active antiretroviral therapy. The health care workers and experts working at the ART clinic should focus on patient counseling regarding the early prevention, detection, and treatment of opportunistic infections. Early health-seeking behaviors before the AIDs stage and critical follow-up are the first actions to identify undernutrition.

Clinical characteristics and outcomes in carbohydrate antigen 19-9 negative pancreatic cancer.

BACKGROUNDPancreatic ductal adenocarcinoma (PDAC) is a leading cause of death from cancer worldwide. Tumor markers like carbohydrate antigen 19-9 (CA 19-9) have been proven valuable as a diagnostic tool and a predictor for tumor staging and response to therapy.AIMTo delineate the phenotype of normal CA 19-9 PDAC according to clinical features, disease staging and prognosis as compared with high CA 19-9 PDAC cases.METHODSWe performed a retrospective single-center analysis of all PDAC cases admitted in our Gastroenterology department over a period of 30 mo that were diagnosed by endoscopic ultrasound-guided tissue acquisition. Patients were divided into two groups according to CA 19-9 levels over a threshold of 37 U/mL. We performed a comparison between the two groups with regard to demographic and clinical data, biomarkers, tumor staging and 6-mo survival.RESULTSAltogether 111 patients were recruited with 29 having documented normal CA 19-9 (< 37 U/mL). In the CA 19-9 negative group of patients, 20.68% had elevated levels of both CEA and CA 125, 13.79% for CA 125 only whilst 17.24% for CEA only. The two groups had similar demographic characteristics. Abdominal pain was more frequently reported in positive vs negative CA 19-9 PDAC cases (76.83% vs 55.17%), while smoking was slightly more prevalent in the latter group (28.04% vs 31.03%). Tumors over 2 cm were more frequently seen in the positive CA 19-9 group, reflecting a higher proportion of locally advanced and metastatic neoplasia (87.7% vs 79.3%). Six-month survival was higher for the negative CA 19-9 group (58.62% vs 47.56%).CONCLUSIONElevated CA 19-9 at diagnosis seems to be associated with a more pronounced symptomatology, high tumor burden and poor prognosis compared to negative CA 19-9 PDAC cases. CEA and CA 125 can be adjunctive useful markers for PDAC, especially in CA 19-9 negative cases.

FXYD3 Expression Predicts Poor Prognosis in Renal Cell Carcinoma with Immunosuppressive Tumor Microenvironment.

Simple SummaryFXYD3 belongs to the protein-coding gene family associated with Na+/K+-ATPase enzymes and chloride ion channels. Recently, the biological role of FXYD3 has been reported in multiple cancers. Nevertheless, the prognostic value of FXYD3 expression has been undiscovered in clear renal cell carcinoma (KIRC). In this study, we assessed the datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset (GSE29609). We found the FXYD3 high KIRC patients had distinct clinical characteristics, including hypoxia and poor overall survival. Furthermore, the algorithms discovered that FXYD3 mRNA levels were associated with tumor purity, multiple types of the tumor infiltrating lymphocytes (TILs) and several genes related to T cell exhaustion. In conclusion, FXYD3 predicts a poor prognosis associated with hypoxia, pro-tumor TILs, and T cell exhaustion in KIRC.FXYD3 is a protein-coding gene, belonging to the FXYD protein family associated with Na+/K+-ATPase enzymes and chloride ion channels. Accumulating evidence suggests the biological role of FXYD3 in multiple cancers. However, the prognostic value of FXYD3 expression in clear renal cell carcinoma (KIRC) is unclear. Therefore, we evaluated the clinical data with tumor-infiltrating lymphocytes (TILs) and immunoinhibitory gene expression data using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset (GSE29609). First, the FXYD3 high KIRC patients had distinct clinical characteristics, including age, sex, disease stage, histological grade, and hypoxia-related gene expressions. Next, FXYD3 gene expression was correlated with poor overall survival in both TCGA and GSE29609 cohorts. The ESTIMATE algorithm revealed that higher FXYD3 mRNA levels were associated with increased infiltration of immune cells and tumor purity. Moreover, the FXYD3 high KIRC tissue harbored increased TILs such as B cells, CD8+ T cells, and M1 macrophage, whereas NK cells and neutrophils were decreased. In addition, we showed FXYD3 was co-expressed with several immunoinhibitory genes related to T cell exhaustion such as LGALS9, CTLA4, BTLA, PDCD1, and LAG3. In conclusion, FXYD3 is an unfavorable prognostic biomarker associated with hypoxia, pro-tumor TILs, and T cell exhaustion.

Amygdala abnormalities across disease stages in patients with sporadic amyotrophic lateral sclerosis.

To examine selective atrophy patterns and resting-state functional connectivity (FC) alterations in the amygdala at different stages of amyotrophic lateral sclerosis (ALS), and to explore any correlations between amygdala abnormalities and neuropsychiatric symptoms. We used the King's clinical staging system for ALS to divide 83 consecutive patients with ALS into comparable subgroups at different disease stages. We explored the pattern of selective amygdala subnucleus atrophy and amygdala-based whole-brain FC alteration in these patients and 94 healthy controls (HCs). Cognitive and emotional functions were also evaluated using a neuropsychological test battery. There were no significant differences between ALS patients at King's stage 1 and HCs for any amygdala subnucleus volumes. Compared with HCs, ALS patients at King's stage 2 had significantly lower left accessory basal nucleus and cortico-amygdaloid transition volumes. Furthermore, ALS patients at King's stage 3 demonstrated significant reductions in most amygdala subnucleus volumes and global amygdala volumes compared with HCs. Notably, amygdala-cuneus FC was increased in ALS patients at King's stage 3. Specific subnucleus volumes were significantly associated with Mini-Mental State Examination scores and Hamilton Anxiety Rating Scale scores in ALS patients. In conclusions, our study provides a comprehensive profile of amygdala abnormalities in ALS patients. The pattern of amygdala abnormalities in ALS patients differed greatly across King's clinical disease stages, and amygdala abnormalities are an important feature of patients with ALS at relatively advanced stages. Moreover, our findings suggest that amygdala volume may play an important role in anxiety and cognitive dysfunction in ALS patients.

Evaluation of Asymptomatic Malaria Antigenaemia and Parasitaemia in Human Immunodeficiency Virus-Infected Children in Benin City, Nigeria

Background: Malaria and HIV/AIDS are rampant in subSaharan Africa with prevalence of one reinforcing the other and control of one impactful on control of the other. Malaria parasitaemia (MP) prevalence is increased in HIV-infected individuals while certain drugs used in latter cause decline in MP but it is uncertain how they affect malaria antigenaemia (MA). How certain bio-social and disease characteristics affect MA and MP in this cohort is unknown.&#x0D; Objectives: To determine prevalence of asymptomatic MP and MA and their clinical and social determinants in HIV infected.&#x0D; Methods: In a prospective cross-sectional study carried out at the University of Benin Teaching Hospital (April to June 2016), 221 HIV-infected children (aged 1-17years) asymptomatic for malaria and 221 apparently healthy HIV-negative controls were studied. MA was assessed using rapid diagnostic test while MP was evaluated using microscopy. Standard method was used to determine parasite count.&#x0D; Results: Prevalence of asymptomatic MP was 24.4% in subjects and 17.6% in controls while MA prevalence in subjects and controls were comparable (20.8% vs 18.1%). Malaria parasitaemia rate (MPr) of 24.4% was higher than malaria antigenaemia rate (MAr) (20.8%). MP and MA rates were independent of socioeconomic status, access to anti-retroviral drugs, their duration of use and clinical disease stage.&#x0D; Conclusion: MA occurred frequently enough to warrant its use as malaria case definition surrogate in asymptomatic children with HIV/AIDS receiving trimethoprim-sulfamethoxazole prophylaxis and protease inhibitors.&#x0D; Authors&#x0D; M O Ibadin 1, N Eghafona 2

Sexual maturation of HIV-infected and uninfected male children in Abakaliki, South-East, Nigeria: a cross-sectional study.

IntroductionHIV infection, through various mechanisms causes a derangement in sexual maturation. This study compared the Marshal and Tanner staging of HIV-infected and uninfected males. The aim of the study was to determine the sexual maturation in male children infected with HIV on HAART in Abakaliki.Methodsthis was a cross-sectional and comparative study involving 80 HIV-infected boys aged 8-17 years and 80 uninfected counterparts matched for age and socio-economic class. Stages of sexual maturation (testicular size and pubic hair) were determined according to the method proposed by Marshall and Tanner. The testicular size was measured using an orchidometer. Data analysis was done with SPSS version 20. Structured questionnaire was used to collect information on socio-demographics.Resultsassessment of pubic hair development, showed that 45 (56.2%) of the subjects were in the pre-pubertal stage compared to 27 (33.8%) among the controls, this relationship was statistically significant (p=0.005, OR = 2.5, C.I=1.3-4.8). The mean testicular volume among subjects was found to be 8.29 ± 8.26mls compared to 11.57 ± 8.26mls found in controls. This relationship was also statistically significant. There were significant statistical relationships between duration on HAART and clinical stages of disease with both pubic hair development and testicular volume of subjects and controls.ConclusionHIV-infected males had significantly delayed onset and progression of sexual maturation. Routine assessment of the sexual maturation of HIV-infected children as well as addressing the modifiable variables influencing sexual maturity is recommended.

Abstract 3686: Differences in disease presentation, and treatment outcomes of neoadjuvant chemotherapy for breast cancer among Hispanics in a minority-serving institution

Abstract Background: Response to neoadjuvant chemotherapy (NAC) for breast cancer varies by tumor characteristics and therapy regimen. Studies suggest that patient ethnicity is associated with differences in disease presentation, response to treatment, and outcomes. There exists a paucity of literature on the presentation and outcomes of NAC for breast cancer in Hispanic women. Methods: This is an IRB-approved retrospective study of breast cancer patients who underwent NAC at an NCI-designated Comprehensive Cancer Center from 2005-2020. We reviewed demographics, disease presentation, response to treatment, and outcomes. ER and PR status were categorized as low positive (1-9%), positive (≥ 10%) and negative. Treatment factors reviewed included completion of chemotherapy and type of surgery performed. Treatment response was noted as percent residual cellularity (0%, &amp;lt;10%, 10-30%, &amp;gt;30-80% and &amp;gt;80%) in the surgical specimen and pathologic stage. Outcomes were assessed as overall survival (OS) and recurrence. Results: 365 patients received neoadjuvant chemotherapy from 2005-2020, and 196 (53.7%) self-identified as Hispanic. Median follow-up was 13.65 years. Highest clinical stage at diagnosis was most frequently IIA (31.2%), followed by IIB (32.3%), with non-significant Hispanic ethnicity differences, although Hispanic patients presented with higher clinical prognostic stages: IIIA or higher (40.5% vs. 24.0%). Hispanics more frequently had grade 3 tumors (60% vs. 48%), ER low positive (10% vs. 7%) and ER negative (48% vs. 36%) (p=0.02). No significant differences were noted in triple negative disease or HER2 positive disease. Hispanics were diagnosed at younger average ages (48.9 vs. 53.0 years, p=0.001). No statistically significant differences were noted in time from diagnosis to NAC initiation, completion of chemotherapy, or surgical treatment received (lumpectomy vs. mastectomy, and sentinel node biopsy vs. dissection). Mastectomy was more likely for late-stage disease (OR=2.73, 95% CI: 1.66-4.49, p&amp;lt;0.001); Hispanic women with late-stage disease had 1.09-fold higher odds of receiving mastectomy, but this was non-significant (95% CI: 0.66-1.79). No significant ethnic differences were noted in pCR (p=0.69) or residual tumor cellularity (p=0.63). There was no significant association between residual cellularity and OS. OS rates were similar for Hispanic vs. Non-Hispanic women (HR: 1.15, 95% CI: 0.64-2.08, p=0.63). No difference was noted in ethnicity-based recurrence rates (21.4 vs. 20.1%). Conclusion: Self-identified Hispanic patients were diagnosed at a younger age, presented with higher ER negative and low-positive disease and worse prognostic clinical stage. However, given standard of care chemotherapy, there were no significant differences in their treatment response or outcomes compared to non-Hispanic patients. Citation Format: Sangeetha Prabhakaran, Christopher McNicoll, Vernon S. Pankratz, Nadja Falk, Jacklyn Nemunaitis, Jain Zhou, Payton A. Sandoval-Belt. Differences in disease presentation, and treatment outcomes of neoadjuvant chemotherapy for breast cancer among Hispanics in a minority-serving institution [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3686.

Gastrectomy for elderly gastric cancer patients: A propensity score-matching analysis.

Although D2-gastrectomy is the most effective treatment for resectable gastric cancer (GC), it is unclear whether elderly patients have increased risk of morbidity and worse survival. This study aimed to compare the short- and long-term outcomes of older age (OA) patients with those of less advanced age (LAA). GC patients undergoing curative gastrectomy were retrospectively analyzed and divided into two groups: OA (>75 years) and LAA (<75 years). Propensity score-matching (PSM) analysis using seven variables was conducted to reduce selection bias. Among 586 patients, 494 (84.3%) were classified as LAA and 92 (15.7%) as OA. OA patients had worse clinical status, higher rates of D1-lymphadenectomy, subtotal gastrectomy, and Lauren type; higher mortality and worse survival. No difference in pathological tumor-node-metastasis (pTNM) stage was observed between groups. Preoperative chemotherapy was performed more frequently in the LAA group. After PSM (92 OA: 92 LAA), all variables included in PSM were matched, and mortality rates and survival became similar between groups. In multivariate analysis, American Society of Anaesthesiologists score III/IV was an independent factor associated with a 90-day mortality after PSM. Gastrectomy in elderly GC patients has similar outcomes compared with younger ones. Clinical status and disease stage are more important than the patient's age.

Radiation therapy and associated cardiovascular outcomes in patients with Hodgkin’s lymphoma.

e19528 Background: Hodgkin’s lymphoma (HL) is a lymphoid neoplasm, with lymphadenopathy with constitutional symptoms as presenting manifestations. The treatment is guided by the clinical stage of disease, and is curable in about 75% of the patients. Advances in cancer therapeutics have improved survival rates, however treatment-related toxicities have become a competing cause of late mortality. Radiation therapy (RT) and chemotherapy have historically been the pillars of curative treatments for HL. RT to the thorax is associated with substantial risk for the development of cardiovascular (CV) disease including pericardial disease, coronary artery disease, valvular disease, conduction disease, cardiomyopathy. The true incidence of radiation-related cardiovascular disease remains uncertain due to lack of large multi-centre studies with a sufficient duration of CV follow-up. Through this study we aim to determine the CV co-morbidities and outcomes of patients with HL treated with and without RT. Methods: We identified hospitalized adult patients with HL and divided them into patients with and without history of radiation therapy from October 2015 to December 2018 from the National Inpatient Sample Database using ICD 10 codes. We further determined demographics, baseline characteristics, associated CV co-morbidities, mortality, length of stay and hospitalization costs among patients with HL with and without history of RT. SAS 9.4 software was used for statistical analysis. Results: We captured 86,325 patients hospitalized with HL during the study period out of which 11,030 patients had history of RT. The patient cohort with RT was noted to have higher prevalence of hypertension (40.7 vs 37.1%), heart failure with reduced ejection fraction (9.2 vs 6.4%), heart failure with preserved ejection fraction (9.2 vs 5.9%), coronary artery disease (33.6 vs 20.3%), atrial fibrillation (19.2 vs 14%), aortic valve disease (10.1 vs 3.8%), mitral valve disease(5.6 vs 2.7%), pulmonary hypertension (9.6 vs 4.6%), and pleural effusion(9.7 vs 6.8%) as compared to patients without history of RT. The study did not show any statistically significant difference in length of stay or in-hospital mortality in the two groups. Conclusions: This study revealed significantly higher prevalence of multiple CV co-morbidities among HL survivors treated with RT. CV disease is now the most common non malignancy related cause of death in radiation-treated cancer survivors. Awareness and early identification of cardiac complications is crucial survivors. There are currently no consensus guidelines to dictate the optimal surveillance of recipients of thoracic radiation. Therefore through this study we aim to shine light on the importance of early surveillance and collaboration between oncologists and cardiologists in the management of the cancer survivors with history of RT.

Is there a relationship between clinical stage and cardiovascular disease risk in bipolar disorder?

Introduction Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in bipolar disorders(BD). The heart age of patients with BD was found to be 8.5 years higher than gender-age matched health controls. Metabolic side effects of antipsychotics, poor diet, insufficient physical activity, smoking and sedentary life style increase the risk of cardiovascular disease in bipolar patients. QRISK-3 is an approved risk classification that calculates the 10-year risk of developing a heart attack or stroke.ObjectivesThis study aims to determine whether there is a difference between cardiovascular disease risk scores and clinical stages of bipolar disorderMethods35 outpatients that were followed up in Selcuk University Medical Faculty were evaluated. The clinical stages and qrisk3 scores were calculated.Results68.6% (n:24) of the patients were female. 42.9% of patients were in stage 3b (recurrent relapses, complete remission between episodes). The mean age was 36.94 ±10.46 years. The mean heart age was 50.54±17.35. The mean Q risk3 score was 5.59±8.18. There was no difference between bipolar patients at stage 2 and stage 3 in terms of age(p=0.36 and gender(p=0.73). When we compared the qrisk3 total socres and heart age of the patients in stage 2 and 3, we could not find any difference between groups (p=0.74, p=0.57 respectively).ConclusionsEven though we could not find any difference of qrisk scores at different clinical stages of patients with BD, the CVD risk increases with the age. Prospective longitudinal follow-up studies are required to evaluate dual interaction of clinical stages and CVD risk in BD.DisclosureNo significant relationships.

Multiscale in silico knowledge-based model predicts tumor growth in advanced EGFR+ NSCLC patients on gefitinib.

e20565 Background: Tumor heterogeneity and treatment resistance remains a continued threat to patients with advanced non-small cell lung cancer (NSCLC), despite the emergence of targeted medicines, e.g. against epidermal growth factor receptor (EGFR) alterations. We developed an in silico EGFR mutated lung adenocarcinoma (EGFR+ LUAD) model to predict the effect of known oncogenic EGFR mutations (common EGFR mutations, EGFR exon 20 insertions). The model provides mechanistic representation of tumor progression, including response to gefitinib and captures tumor heterogeneity, patient age, gender, initial clinical disease stage, and smoking status. Methods: 5-step in silico model development: Model building: biology of EGFR+LUAD was characterized by extracting biological features and their functional relationships from &gt; 300 published papers and translating them into ordinary differential equations (ODEs). Mutational burden, EGFR-downstream-pathways, tumor growth and heterogeneity, gefitinib-PK/PD, treatment-induced resistance and clinical outcome were incorporated into a knowledge-based model containing 27-97 variables, 108-258 parameters and 13-83 ODEs reflecting intra-tumor clonal heterogeneity in a mechanistic manner. Calibration: published spheroid, xenograft and clinical data were used for stepwise calibration to find the correct parameter values. Relevant virtual populations (VPOPs) matching real patients baseline characteristics were generated for model benchmarking and validation. Benchmarking against a published data-based model: coverage of experimental interquartile range (IQR) with simulated IQR (precision) assesses model fit with experimental data, coverage of simulated IQR with experimental IQR (overlap) assesses model fit with experimental variability. Validation: a VPOP with comparable baseline characteristics was simulated and results compared against a published patient dataset that wasn’t used in any step during calibration. Matching of prediction over clinical data was done using both coverage and bootstrapped log-rank metrics. Results: Our model provides comparable outputs to the data-based model without having access to the exact original data (our model: precision of 62%, overlap of 91% VS data-based model: precision of 72% and an overlap of 86%). Besides, as a validation criterion, our model also successfully reproduces the time to progression observed in an independent clinical trial (coverage &gt; 99%, negative log-rank tests &gt; 98%). Conclusions: We simulated tumor growth and treatment response in advanced EGFR+ LUAD patients and successfully validated results both against an existing data-based model and a published clinical data. Our model highlights the potential of in silico modeling to better understand complex diseases progression and support efficient development of innovative therapies.

Ginkgo biloba protects striatal neurodegeneration and gut phagoinflammatory damage in rotenone-induced mice model of Parkinson's disease: Role of executioner caspase-3/Nrf2/ARE signaling.

Asymptomatic and early clinical stages of Parkinson's disease (PD) have been linked with comorbid non-motor symptoms including dysfunction of the gastrointestinal (GI) tract. Notwithstanding, neuroprotective and gastroprotective effects of Ginkgo biloba supplements (GBS) have been investigated independently. Hence, whether GBS-mediated GIT-protective capacity could be helpful in PD via gut-brain anti-inflammatory signaling still remains unknown. Treatment with GBS significantly repressed the motor behavioral and neuromuscular deficits and prevented loss of striatal dopaminergic loss by improving the level of tyrosine hydroxylase enzyme and suppressing synucleinopathy development. Striatal neurons and ileal epithelial injury following intraperitoneal rotenone administration were accompanied with oxidoinflammatory/nitroinflammatory stress and marked inhibition of cholinergic transmission. Moreover, there was increased striatal executioner caspase-3 and decreased nuclear factor erythroid-2-related factor 2 (Nrf2) immunoexpression, loss of striatal pyramidal neuron with a marked decrease in length and width of the dendritic spines as well as significant hyperplasia of cryptal cells in the ileal epithelial tissues, all which were reversed by the pretreatment + concurrent (Pre-CONC) and concurrent (CONC) GBS treatment pattern. In sum, we proved the potential dual effects of GBS in preventing both dopaminergic neural-related impairments and gut wall abnormalities linked with PD.

Parkinson’s disease clinical milestones and mortality

Identification of factors predicting and driving mortality in PD is important for patient information, disease management, and design of future clinical trials. This study included newly diagnosed PD patients and normal controls (NC) from a population-based study with repeated assessments over a 10-year period. We used the Kaplan–Meier method to estimate survival, Cox proportional hazards regression models to identify baseline risk factors of mortality, and Cox regression models with time-dependent covariates to evaluate the impact of four clinical milestones of advanced PD (visual hallucinations, recurrent falls, dementia, and nursing home placement) on mortality risk. During the 10-year study, 65 (34.2%) of 190 patients and 25 (12.3%) of 203 NC died, with an unadjusted hazard ratio (HR) of 2.85 (95% CI 1.80–4.52) and a HR of 2.48 (95% CI 1.55–3.95) when adjusted for confounders, including comorbidities. Higher age, more severe motor impairment, and postural instability-gait difficulty (PIGD) phenotype were independent baseline predictors of mortality. Each clinical milestone alone more than doubled the risk of death and had a cumulative effect on mortality, with a HR of 10.83 (95% CI 4.39–26.73) in those experiencing all four milestones. PD patients have an increased mortality risk that is disease-related and becomes evident early during the course of the disease. While motor severity and PIGD phenotype were early risk factors of mortality, clinical milestones signaled a substantially increased risk of death later during the disease course, highlighting their potential significance in clinical disease staging and prognosis.

MP23-07 PREVALENCE AND IMPACT OF FEAR OF RECURRENCE ON BLADDER CANCER PATIENTS AFTER RADICAL CYSTECTOMY

You have accessJournal of UrologyCME1 May 2022MP23-07 PREVALENCE AND IMPACT OF FEAR OF RECURRENCE ON BLADDER CANCER PATIENTS AFTER RADICAL CYSTECTOMY Justin Badal, Brady Miller, Nora Ruel, Airybelle Uchida, Kelly Franklin, Sumanta Pal, and Bertram Yuh Justin BadalJustin Badal More articles by this author , Brady MillerBrady Miller More articles by this author , Nora RuelNora Ruel More articles by this author , Airybelle UchidaAirybelle Uchida More articles by this author , Kelly FranklinKelly Franklin More articles by this author , Sumanta PalSumanta Pal More articles by this author , and Bertram YuhBertram Yuh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002562.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The recurrence rate for bladder cancer is high. Over 30% of those with muscle invasive bladder cancer have a recurrence within 5 years representing a source of persistent anxiety and distress. Fear of cancer recurrence (FCR) is well characterized in other malignancies such as breast, thyroid, and brain cancers. It has been characterized in prostate, renal, and testis cancer. This study describes the prevalence and impact of FCR among patients with bladder cancer who have had cystectomy. METHODS: A phone survey was conducted using the Fear of Cancer Recurrence-7 index in patients who had previously undergone radical cystectomy for bladder cancer. From the period of 2015 to 2020, 145 patients were eligible to undergo the phone survey. 75 patients agreed to being surveyed. We evaluated patients based on factors such as time since surgery, clinical and pathologic stage, receipt of neoadjuvant chemotherapy, ASA status, and length of stay. RESULTS: The median age for participants was 70. 83% of respondents were male. 84% of respondents were white. 39 patients had muscle invasive disease at presentation and 17 patients had muscle invasive disease on pathologic staging. Median time since surgery was 28 months. 17% of patients had high (FCR7 ≥17) scores. Those with lower clinical and pathologic stage disease had higher FCR7 scores. 12/58 (21%) patients with ≤PT1 reported a high FCR while only 1/17 (6%) of patients with ≥pT2 disease reported high FCR (p=0.11). Their FCR7 score was more likely to be ≥17 in the 2nd or 3rd year from surgery. Patients who underwent Indiana Pouch urinary diversion were more likely to have a FCR7≥17 when compared to ileal conduit or Studer neobladder (44.4% vs 13.6%, p=0.022). CONCLUSIONS: Fear of cancer recurrence in patients with bladder cancer is a phenomenon that should be considered when counseling patients in the preoperative as well as surveillance stages of their cancer care. Even after several years, patients who have FCR continue to exhibit persistent fear. Patients with certain forms of urinary diversion may also have differing FCR. Though not statistically significant, patients with lower stage disease may require closer psychologic monitoring through their cancer treatment journey. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e383 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Justin Badal More articles by this author Brady Miller More articles by this author Nora Ruel More articles by this author Airybelle Uchida More articles by this author Kelly Franklin More articles by this author Sumanta Pal More articles by this author Bertram Yuh More articles by this author Expand All Advertisement PDF DownloadLoading ...