1112 THE IMPACT OF PRE-TREATMENT CHARACTERISTICS ON MANAGEMENT OF THE STAGE I RENAL MASS

AbstractEarly detection and intervention are believed to be key to facilitating better outcomes in children with autism, yet the impact of age at treatment start on the outcome is poorly understood. While clinical traits such as language ability have been shown to predict treatment outcome, whether or not and how information at the genomic level can predict treatment outcome is unknown. Leveraging a cohort of toddlers with autism who all received the same standardized intervention at a very young age and provided a blood sample, here we find that very early treatment engagement (i.e., <24 months) leads to greater gains while controlling for time in treatment. Pre-treatment clinical behavioral measures predict 21% of the variance in the rate of skill growth during early intervention. Pre-treatment blood leukocyte gene expression patterns also predict the rate of skill growth, accounting for 13% of the variance in treatment slopes. Results indicated that 295 genes can be prioritized as driving this effect. These treatment-relevant genes highly interact at the protein level, are enriched for differentially histone acetylated genes in autism postmortem cortical tissue, and are normatively highly expressed in a variety of subcortical and cortical areas important for social communication and language development. This work suggests that pre-treatment biological and clinical behavioral characteristics are important for predicting developmental change in the context of early intervention and that individualized pre-treatment biology related to histone acetylation may be key.

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Time-to-Treatment in Oral Cancer: Causes and Implications for Survival

Cancers ◽

10.3390/cancers13061321 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1321

Author(s):

Constanza Saka-Herrán ◽

Enric Jané-Salas ◽

Antoni Mari-Roig ◽

Albert Estrugo-Devesa ◽

José López-López

Keyword(s):

Oral Cancer ◽

Previous Treatment ◽

Diagnostic Procedures ◽

Original Data ◽

Primary Treatment ◽

Medical Attention ◽

Time Interval ◽

Pre Treatment ◽

The Impact ◽

Lack Of Knowledge

The purpose of this review was to identify and describe the causes that influence the time-intervals in the pathway of diagnosis and treatment of oral cancer and to assess its impact on prognosis and survival. The review was structured according to the recommendations of the Aarhus statement, considering original data from individual studies and systematic reviews that reported outcomes related to the patient, diagnostic and pre-treatment intervals. The patient interval is the major contributor to the total time-interval. Unawareness of signs and/or symptoms, denial and lack of knowledge about oral cancer are the major contributors to the process of seeking medical attention. The diagnostic interval is influenced by tumor factors, delays in referral due to higher number of consultations and previous treatment with different medicines or dental procedures and by professional factors such as experience and lack of knowledge related to the disease and diagnostic procedures. Patients with advanced stage disease, primary treatment with radiotherapy, treatment at an academic facility and transitions in care are associated with prolonged pre-treatment intervals. An emerging body of evidence supports the impact of prolonged pre-treatment and treatment intervals with poorer survival from oral cancer.

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Comparison of Selected Immune and Hematological Parameters and Their Impact on Survival in Patients with HPV-Related and HPV-Unrelated Oropharyngeal Cancer

Cancers ◽

10.3390/cancers13133256 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3256

Author(s):

Adam Brewczyński ◽

Beata Jabłońska ◽

Agnieszka Maria Mazurek ◽

Jolanta Mrochem-Kwarciak ◽

Sławomir Mrowiec ◽

...

Keyword(s):

Prognostic Factors ◽

Oropharyngeal Cancer ◽

Hematological Parameters ◽

White Blood Cells ◽

Post Treatment ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Hpv Status ◽

Pre Treatment ◽

The Impact

Several immune and hematological parameters are associated with survival in patients with oropharyngeal cancer (OPC). The aim of the study was to analyze selected immune and hematological parameters of patients with HPV-related (HPV+) and HPV-unrelated (HPV-) OPC, before and after radiotherapy/chemoradiotherapy (RT/CRT) and to assess the impact of these parameters on survival. One hundred twenty seven patients with HPV+ and HPV− OPC, treated with RT alone or concurrent chemoradiotherapy (CRT), were included. Patients were divided according to HPV status. Confirmation of HPV etiology was obtained from FFPE (Formalin-Fixed, Paraffin-Embedded) tissue samples and/or extracellular circulating HPV DNA was determined. The pre-treatment and post-treatment laboratory blood parameters were compared in both groups. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), and systemic immune inflammation (SII) index were calculated. The impact of these parameters on overall (OS) and disease-free (DFS) survival was analyzed. In HPV+ patients, a high pre-treatment white blood cells (WBC) count (>8.33 /mm3), NLR (>2.13), SII (>448.60) significantly correlated with reduced OS, whereas high NLR (>2.29), SII (>462.58) significantly correlated with reduced DFS. A higher pre-treatment NLR and SII were significant poor prognostic factors for both OS and DFS in the HPV+ group. These associations were not apparent in HPV− patients. There are different pre-treatment and post-treatment immune and hematological prognostic factors for OS and DFS in HPV+ and HPV− patients. The immune ratios could be considered valuable biomarkers for risk stratification and differentiation for HPV− and HPV+ OPC patients.

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The impact of sociodemographic factors on the utilization of radiation therapy in breast cancer patients in Estonia: a register-based study

International Journal for Equity in Health ◽

10.1186/s12939-021-01497-0 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Fereshteh Shahrabi Farahani ◽

Keiu Paapsi ◽

Kaire Innos

Keyword(s):

Breast Cancer ◽

Radiation Therapy ◽

Cancer Registry ◽

Psychosocial Support ◽

Sociodemographic Factors ◽

Stage I ◽

Equal Access ◽

Administrative Databases ◽

The Impact ◽

Over Time

Abstract Background Radiation therapy is an important part of multimodal breast cancer treatment. The aim was to examine the impact of sociodemographic factors on radiation therapy use in breast cancer (BC) patients in Estonia, linking cancer registry data to administrative databases. Methods Estonian Cancer Registry provided data on women diagnosed with BC in Estonia in 2007–2018, including TNM stage at diagnosis. Use of radiation therapy within 12 months of diagnosis was determined from Estonian Health Insurance Funds claims, and sociodemographic characteristics from population registry. Receipt of radiation therapy was evaluated over time and by clinical and sociodemographic factors. Poisson regression with robust variance was used to calculate univariate and multivariate prevalence rate ratios (PRR) with 95 % confidence intervals (CI) for receipt of radiation therapy among stage I–III BC patients age < 70 years who underwent primary surgery. Results Overall, of 8637 women included in the study, 4310 (50 %) received radiation therapy within 12 months of diagnosis. This proportion increased from 39 to 58 % from 2007 to 2009 to 2016–2018 (p < 0.001). Multivariate regression analysis showed that compared to women with stage I BC, those with more advanced stage were less likely to receive radiation therapy. Receipt of radiation therapy increased significantly over time and was nearly 40 % higher in 2016–2018 than in 2007–2009. Use of radiation therapy was significantly lower for women with the lowest level of education compared to those with a university degree (PRR 0.88, 95 % CI 0.80–0.97), and for divorced/widowed women (PRR 0.95, 95 % CI 0.91–0.99) and single women (PRR 0.92, 95 % CI 0.86–0.99), compared to married women. Age at diagnosis, nationality and place of residence were not associated with receipt of radiation therapy. Conclusions The study showed considerable increase in the use of radiation therapy in Estonia over the study period, which is in line with increases in available equipment. The lack of geographic variations suggests equal access to therapy for patients living in remote regions. However, educational level and marital status were significantly associated with receipt of radiation therapy, highlighting the importance of psychosocial support in ensuring equal access to care.

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Porphyromonas Gingivalis Infection Induces Synaptic Failure via Increased IL-1β Production in Leptomeningeal Cells

Journal of Alzheimer s Disease ◽

10.3233/jad-210031 ◽

2021 ◽

pp. 1-17

Author(s):

Wanyi Huang ◽

Fan Zeng ◽

Yebo Gu ◽

Muzhou Jiang ◽

Xinwen Zhang ◽

...

Keyword(s):

Porphyromonas Gingivalis ◽

Nlrp3 Inflammasome ◽

Cortical Neurons ◽

Inflammasome Activation ◽

Memory Decline ◽

Periodontal Bacteria ◽

Nlrp3 Inflammasome Activation ◽

Synaptic Failure ◽

Pre Treatment ◽

The Impact

Background: Studies have reported that synaptic failure occurs before the Alzheimer’s disease (AD) onset. The systemic Porphyromonas gingivalis (P. gingivalis) infection is involved in memory decline. We previously showed that leptomeningeal cells, covering the brain, activate glial cells by releasing IL-1β in response to systemic inflammation. Objective: In the present study, we focused on the impact of leptomeningeal cells on neurons during systemic P. gingivalis infection. Methods: The responses of leptomeningeal cells and cortical neurons to systemic P. gingivalis infection were examined in 15-month-old mice. The mechanism of IL-1β production by P. gingivalis infected leptomeningeal cells was examined, and primary cortical neurons were treated with P. gingivalis infected leptomeningeal cells condition medium (Pg LCM). Results: Systemic P. gingivalis infection increased the expression of IL-1β in leptomeninges and reduced the synaptophysin (SYP) expression in leptomeninges proximity cortex in mice. Leptomeningeal cells phagocytosed P. gingivalis resulting in lysosomal rupture and Cathepsin B (CatB) leakage. Leaked CatB mediated NLRP3 inflammasome activation inducing IL-1β secretion in leptomeningeal cells. Pg LCM decreased the expression of synaptic molecules, including SYP, which was inhibited by an IL-1 receptor antagonist pre-treatment. Conclusion: These observations demonstrate that P. gingivalis infection is involved in synaptic failure by inducing CatB/NLRP3 inflammasome-mediated IL-1β production in leptomeningeal cells. The periodontal bacteria-induced synaptic damage may accelerate the onset and cognitive decline of AD.

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Mechanical, Thermal and Rheological Properties of Polyethylene-Based Composites Filled with Micrometric Aluminum Powder

Materials ◽

10.3390/ma13051242 ◽

2020 ◽

Vol 13 (5) ◽

pp. 1242

Author(s):

Olga Mysiukiewicz ◽

Paulina Kosmela ◽

Mateusz Barczewski ◽

Aleksander Hejna

Keyword(s):

Mechanical Properties ◽

Melt Flow Index ◽

Tensile Tests ◽

Mechanical Analysis ◽

Flow Index ◽

Scanning Calorimetry ◽

Metal Composites ◽

Pre Treatment ◽

The Impact ◽

Properties Of Composites

Investigations related to polymer/metal composites are often limited to the analysis of the electrical and thermal conductivity of the materials. The presented study aims to analyze the impact of aluminum (Al) filler content (from 1 to 20 wt%) on the rarely investigated properties of composites based on the high-density polyethylene (HDPE) matrix. The crystalline structure, rheological (melt flow index and oscillatory rheometry), thermal (differential scanning calorimetry), as well as static (tensile tests, hardness, rebound resilience) and dynamic (dynamical mechanical analysis) mechanical properties of composites were investigated. The incorporation of 1 and 2 wt% of aluminum filler resulted in small enhancements of mechanical properties, while loadings of 5 and 10 wt% provided materials with a similar performance to neat HDPE. Such results were supported by the lack of disturbances in the rheological behavior of composites. The presented results indicate that a significant content of aluminum filler may be introduced into the HDPE matrix without additional pre-treatment and does not cause the deterioration of composites’ performance, which should be considered beneficial when engineering PE/metal composites.

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Short-Term High Fat Intake Does Not Significantly Alter Markers of Renal Function or Inflammation in Young Male Sprague-Dawley Rats

Journal of Nutrition and Metabolism ◽

10.1155/2015/157520 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Catherine Crinigan ◽

Matthew Calhoun ◽

Karen L. Sweazea

Keyword(s):

Kidney Disease ◽

Renal Mass ◽

Early Stage ◽

Young Male ◽

Protective Effects ◽

Sprague Dawley ◽

High Fat ◽

Short Term ◽

Sprague Dawley Rats ◽

The Impact

Chronic high fat feeding is correlated with diabetes and kidney disease. However, the impact of short-term high fat diets (HFD) is not well-understood. Six weeks of HFD result in indices of metabolic syndrome (increased adiposity, hyperglycemia, hyperinsulinemia, hyperlipidemia, hyperleptinemia, and impaired endothelium-dependent vasodilation) compared to rats fed on standard chow. The hypothesis was that short-term HFD would induce early signs of renal disease. Young male Sprague-Dawley rats were fed either HFD (60% fat) or standard chow (5% fat) for six weeks. Morphology was determined by measuring changes in renal mass and microstructure. Kidney function was measured by analyzing urinary protein, creatinine, and hydrogen peroxide (H2O2) concentrations, as well as plasma cystatin C concentrations. Renal damage was measured through assessment of urinary oxDNA/RNA concentrations as well as renal lipid peroxidation, tumor necrosis factor alpha (TNFα), and interleukin 6 (IL-6). Despite HFD significantly increasing adiposity and renal mass, there was no evidence of early stage kidney disease as measured by changes in urinary and plasma biomarkers as well as histology. These findings suggest that moderate hyperglycemia and inflammation produced by short-term HFD are not sufficient to damage kidneys or that the ketogenic HFD may have protective effects within the kidneys.

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Low value of whole-body dual-modality [18f]fluorodeoxyglucose positron emission tomography/computed tomography in primary staging of stage I–II nasopharyngeal carcinoma: a nest case-control study

European Radiology ◽

10.1007/s00330-020-07478-1 ◽

2021 ◽

Author(s):

Bei-Bei Xiao ◽

Qiu-Yan Chen ◽

Xue-Song Sun ◽

Ji-Bin Li ◽

Dong-hua Luo ◽

...

Keyword(s):

Overall Survival ◽

Lymph Node ◽

Lymph Nodes ◽

Stage I ◽

Relapse Free Survival ◽

Retropharyngeal Lymph Node ◽

Free Survival ◽

Pet Ct ◽

Pre Treatment

Abstract Objectives The value of using PET/CT for staging of stage I–II NPC remains unclear. Hence, we aimed to investigate the survival benefit of PET/CT for staging of early-stage NPC before radical therapy. Methods A total of 1003 patients with pathologically confirmed NPC of stages I–II were consecutively enrolled. Among them, 218 patients underwent both PET/CT and conventional workup ([CWU], head-and-neck MRI, chest radiograph, liver ultrasound, bone scintigraphy) before treatment. The remaining 785 patients only underwent CWU. The standard of truth (SOT) for lymph node metastasis was defined by the change of size according to follow-up MRI. The diagnostic efficacies were compared in 218 patients who underwent both PET/CT and CWU. After covariate adjustment using propensity scoring, a cohort of 872 patients (218 with and 654 without pre-treatment PET/CT) was included. The primary outcome was overall survival based on intention to treat. Results Retropharyngeal lymph nodes were metastatic based on follow-up MRI in 79 cases. PET/CT was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions (72.2% [62.3–82.1] vs. 91.1% [84.8–97.4], p = 0.004). Neck lymph nodes were metastatic in 89 cases and PET/CT was more sensitive than MRI (96.6% [92.8–100.0] vs. 76.4% [67.6–85.2], p < 0.001). In the survival analyses, there was no association between pre-treatment PET/CT use and improved overall survival, progression-free survival, local relapse-free survival, regional relapse-free survival, and distant metastasis-free survival. Conclusions This study showed PET/CT is of little value for staging of stage I–II NPC patients at initial imaging. Key Points • PET/CT was more sensitive than MRI in detecting neck lymph node lesions whereas it was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions. • No association existed between pre-treatment PET/CT use and improved survival in stage I–II NPC patients.

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The impact of the COVID-19 pandemic on stage at diagnosis of breast and colorectal cancers.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.6501 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 6501-6501

Author(s):

Jade Zhou ◽

Shelly Kane ◽

Celia Ramsey ◽

Melody Ann Akhondzadeh ◽

Ananya Banerjee ◽

...

Keyword(s):

Breast Cancer ◽

Colorectal Cancer ◽

Cancer Screening ◽

Late Stage ◽

Stage Iv ◽

Stage I ◽

Screening Programs ◽

Stage Distribution ◽

Number Of Patients ◽

The Impact

6501 Background: Effective cancer screening leads to a substantial increase in the detection of earlier stages of cancer, while decreasing the incidence of later stage cancer diagnoses. Timely screening programs are critical in reducing cancer-related mortality in both breast and colorectal cancer by detecting tumors at an early, curable stage. The COVID-19 pandemic resulted in the postponement or cancellation of many screening procedures, due to both patient fears of exposures within the healthcare system as well as the cancellation of some elective procedures. We sought to identify how the COVID-19 pandemic has impacted the incidence of early and late stage breast and colorectal cancer diagnoses at our institution. Methods: We examined staging for all patients presenting to UCSD at first presentation for a new diagnosis of malignancy or second opinion in 2019 and 2020. Treating clinicians determined the stage at presentation for all patients using an AJCC staging module (8th edition) in the electronic medical record (Epic). We compared stage distribution at presentation in 2019 vs 2020, both for cancers overall and for colorectal and breast cancer, because these cancers are frequently detected by screening. Results: Total numbers of new patient visits for malignancy were similar in 2019 and 2020 (1894 vs 1915 pts), and stage distribution for all cancer patients was similar (stage I 32% in 2019 vs 29% in 2020; stage IV 26% in both 2019 and 2020). For patients with breast cancer, we saw a lower number of patients presenting with stage I disease (64% in 2019 vs 51% in 2020) and a higher number presenting with stage IV (2% vs 6%). Similar findings were seen in colorectal cancer (stage I: 22% vs 16%; stage IV: 6% vs 18%). Conclusions: Since the COVID-19 pandemic, there has been an increase in incidence of late stage presentation of colorectal and breast cancer, corresponding with a decrease in early stage presentation of these cancers at our institution. Cancer screening is integral to cancer prevention and control, specifically in colorectal and breast cancers which are often detected by screening, and the disruption of screening services has had a significant impact on our patients. We plan to continue following these numbers closely, and will present data from the first half of 2021 as it becomes available.

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