LINC-25. BRAF ABERRATIONS IN PEDIATRIC PILOCYTIC ASTROCYTOMAS (PCAs): PREVALENCE AND IMPACT ON CLINICAL OUTCOME

Abstract BACKGROUND Increasing knowledge on pilocytic astrocytoma (PCA) biology now points towards an aberration in BRAF/MAPK/ERK pathway which has both diagnostic and therapeutic implications. This study was done to note the impact of BRAF aberrations on clinical outcome in childhood PCA. METHODS FFPE tissues of all childhood PCA diagnosed during 2011–2017 were evaluated for BRAFV600E mutation by Sanger sequencing and KIAA1549 fusion transcripts (16–9;15–9;16-11) by reverse transcriptase polymerase chain reaction. Children undergoing gross tumor resection received no adjuvant treatment. Unresectable tumors (only biopsy) and NF-1 associated PCAs, were treated if clinically indicated. Only patients with documented therapy details/followup were included for analysis. STUDY RESULTS Ninety-eight patients (median age-7.7yrs; boy:girl ratio-1.4) were included. Major sites were: Cerebellum-37(38%), 3rd Ventricle-26(27%), Cerebrum-15(15%). While BRAFV600E mutation was noted in 7/89(8%) specimens, BRAF-fusions were found in 34/85(40%). Following surgery/biopsy, 23(24%) and 21(22%) received adjuvant chemotherapy and radiotherapy respectively. The 1-year/3-year/5-year-EFS of the overall cohort was 90.7%/81.3%/67.4% respectively. Cerebellar tumors did better vis-à-vis other sites(5yr-EFS:74.3% v/s 66.4%;p=0.403). The 5yr-EFS of BRAF-fusion positive tumors (34), tumors without any BRAF aberration (40) and BRAFV600E mutant tumors (7) was 84.8%/ 69.6%/ 42.9% (p=0.215). CONCLUSIONS BRAF-fusion and BRAFV600E mutation were associated with good and poor outcomes respectively. Lack of statistical significance could be attributed to use of radiation as planned therapy in patients from earlier years. Data on BRAF aberrations in PCAs aids decision making regarding adjuvant therapy and choosing appropriate salvage-therapy especially in relapsed/refractory PCAs.

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Abstract TP4: How Long is Too Long: The Effect of Thrombectomy Procedure Duration on Outcome in Revascularized SWIFT Trial Patients

Stroke ◽

10.1161/str.44.suppl_1.atp4 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Osama Zaidat ◽

Marc A Lazzaro ◽

Scott Brown ◽

Raul G Nogueira ◽

Rishi Gupta ◽

...

Keyword(s):

Clinical Outcome ◽

Neurological Outcome ◽

Statistical Significance ◽

Predictor Variable ◽

Lower Mortality ◽

Good Neurological Outcome ◽

Start Time ◽

Angiographic Data ◽

Procedure Duration ◽

The Impact

Introduction: Thrombectomy procedure start time to recanalization has been may be an important predictor of clinical outcome following endovascular therapy of acute ischemic stroke (AIS) patients. In this study, we sought to assess the impact of groin puncture time to revascularization (procedure duration) on outcomes in the multicenter, randomized Solitaire FR with the Intention for Thrombectomy (SWIFT) trial. Methods: AIS patients enrolled in the SWIFT trial who achieved the primary endpoint of successful recanalization without hemorrhage (SR-sICH) were included. The procedure duration (PD) was defined as time from groin puncture to revascularization. The PD was the main predictor variable. The main outcome variables were the 90 days modified Rankin’s Scale (mRS)≤2; good neurologic outcome (Rankin’s Scale (mRS)≤2 or NIHSS Improvement of≥0), and mortality. Patient demographic, clinical, and angiographic data was reviewed and p-values were calculated using Wilcoxon, linear regression, Cochran Mantel-Haenzsel, or Fischer exact tests. Results: A total of 63 patients achieved SR-sICH and were enrolled in this analysis. A trend of lower mortality rate was noted in those with shorter PD (31(20)) vs. 36(16) minutes,p=0.2). Patients with mRS≤2 had a PD mean time of 36(21) vs. 30(17) minutes,p=0.3. No statistical effect was noted when comparing mortality and mRS within the quartiles of PD time (p=0.39 and p=0.41, respectively). No statistical difference in mRS, good neurological outcome, and mortality when PD dichotomizing to≤1 hour (n=59) vs. >1 hour (n=4). A multivariate model for predicting mRS at 90 days which included PD, age, initial NIHSS, atrial fibrillation, gender, initial systolic and diastolic blood pressure, showed no statistical significance of PD (p=0.8). Conclusions: Thrombectomy procedure duration, defined as time from groin puncture to revascularization, did not show a relationship with mRS or good neurological outcome in revascularized patients of the SWIFT trial. A trend toward lower mortality was noted in patients who had a shorter PD. Additional larger sample size prospective trials are needed to clarify the role of PD on clinical outcome.

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Clinical Features and Molecular Markers on Diffuse Midline Gliomas With H3K27M Mutations: A 43 Cases Retrospective Cohort Study

Frontiers in Oncology ◽

10.3389/fonc.2020.602553 ◽

2021 ◽

Vol 10 ◽

Author(s):

Yuan Wang ◽

Lan-lan Feng ◽

Pei-gang Ji ◽

Jing-hui Liu ◽

Shao-chun Guo ◽

...

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Molecular Markers ◽

Statistical Significance ◽

Tumor Resection ◽

Karnofsky Performance Score ◽

Tertiary Institution ◽

P53 Overexpression ◽

Molecular Alterations ◽

The Impact

PurposeDiffuse midline gliomas (DMG) with H3K27M mutations have been identified as a rare distinctive entity with unique genetic features, varied molecular alterations, and poor prognosis. The current study aimed to evaluate the clinical characteristics and profile of molecular markers on patients with a DMG harboring H3K27M mutations, and explore the impact of this genetic makeup on overall survival.MethodsWe retrospectively analyzed 43 consecutive patients diagnosed with a DMG harboring H3K27M mutations (age range 3 to 75 years) and treated in a tertiary institution within China between January 2017 to December 2019. Various clinical and molecular factors were evaluated to assess their prognostic value in this unique patient cohort.ResultsThe median overall survival (OS) was 12.83 months. Preoperative Karnofsky Performance Score (KPS) and adjuvant radiotherapy were found to be independent clinical parameters influencing the OS by multivariate analysis (p = 0.027 and p < 0.001 respectively). Whereas extent of tumor resection failed to demonstrate statistical significance. For molecular markers, P53 overexpression was identified as a negative prognostic factor for overall survival by multivariate analysis (p = 0.030).ConclusionLow preoperative KPS, absence of radiotherapy and P53 overexpression were identified as predictors of a dismal overall survival in patients with DMG and H3K27M mutations.

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Percutaneous Coronary Intervention in Patients with Diabetes and Multivessel or Left Main Disease – a Review

Interventional Cardiology Review ◽

10.15420/icr.2012.7.1.37 ◽

2012 ◽

Vol 7 (1) ◽

pp. 37

Author(s):

Donald E Cutlip ◽

Keyword(s):

Percutaneous Coronary Intervention ◽

Coronary Artery ◽

Statistical Significance ◽

Bare Metal Stents ◽

Coronary Intervention ◽

Metal Stents ◽

Increased Risk ◽

Percutaneous Coronary ◽

Patients With Diabetes ◽

The Impact

Coronary artery disease in patients with diabetes is frequently a diffuse process with multivessel involvement and is associated with increased risk for myocardial infarction and death. The role of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) in patients with diabetes and multivessel disease who require revascularisation has been debated and remains uncertain. The debate has been continued mainly because of the question to what degree an increased risk for in-stent restenosis among patients with diabetes contributes to other late adverse outcomes. This article reviews outcomes from early trials of balloon angioplasty versus CABG through later trials of bare-metal stents versus CABG and more recent data with drug-eluting stents as the comparator. Although not all studies have been powered to show statistical significance, the results have been generally consistent with a mortality benefit for CABG versus PCI, despite differential risks for restenosis with the various PCI approaches. The review also considers the impact of mammary artery grafting of the left anterior descending artery and individual case selection on these results, and proposes an algorithm for selection of patients in whom PCI remains a reasonable strategy.

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Dietary Patterns: A New Therapeutic Approach for Depression?

Current Pharmaceutical Biotechnology ◽

10.2174/1389201019666180925122116 ◽

2019 ◽

Vol 20 (2) ◽

pp. 123-129 ◽

Cited By ~ 3

Author(s):

Mariana Jesus ◽

Tânia Silva ◽

César Cagigal ◽

Vera Martins ◽

Carla Silva

Keyword(s):

Depressive Symptoms ◽

Dietary Patterns ◽

Large Scale ◽

Randomized Clinical Trials ◽

Dietary Intervention ◽

Common Mental Disorder ◽

Controlled Trial ◽

Statistical Significance ◽

Inverse Association ◽

The Impact

Introduction: The field of nutritional psychiatry is a fast-growing one. Although initially, it focused on the effects of vitamins and micronutrients in mental health, in the last decade, its focus also extended to the dietary patterns. The possibility of a dietary cost-effective intervention in the most common mental disorder, depression, cannot be overlooked due to its potential large-scale impact. Method: A classic review of the literature was conducted, and studies published between 2010 and 2018 focusing on the impact of dietary patterns in depression and depressive symptoms were included. Results: We found 10 studies that matched our criteria. Most studies showed an inverse association between healthy dietary patterns, rich in fruits, vegetables, lean meats, nuts and whole grains, and with low intake of processed and sugary foods, and depression and depressive symptoms throughout an array of age groups, although some authors reported statistical significance only in women. While most studies were of cross-sectional design, making it difficult to infer causality, a randomized controlled trial presented similar results. Discussion: he association between dietary patterns and depression is now well-established, although the exact etiological pathways are still unknown. Dietary intervention, with the implementation of healthier dietary patterns, closer to the traditional ones, can play an important role in the prevention and adjunctive therapy of depression and depressive symptoms. Conclusion: More large-scale randomized clinical trials need to be conducted, in order to confirm the association between high-quality dietary patterns and lower risk of depression and depressive symptoms.

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Glucose Levels and Outcome After Primary Intraventricular Hemorrhage

Current Neurovascular Research ◽

10.2174/1567202616666190131164108 ◽

2019 ◽

Vol 16 (1) ◽

pp. 40-46

Author(s):

Rui Guo ◽

Ruiqi Chen ◽

Chao You ◽

Lu Ma ◽

Hao Li ◽

...

Keyword(s):

Diabetes Mellitus ◽

Blood Glucose ◽

Blood Glucose Level ◽

Incidence Rate ◽

Glucose Level ◽

Intraventricular Hemorrhage ◽

Laboratory Data ◽

History Of ◽

Poor Outcomes ◽

The Impact

Background and Purpose: Hyperglycemia is reported to be associated with poor outcome in patients with spontaneous Intracerebral Hemorrhage (ICH), but the association between blood glucose level and outcomes in Primary Intraventricular Hemorrhage (PIVH) remains unclear. We sought to identify the parameters associated with admission hyperglycemia and analyze the impact of hyperglycemia on clinical outcome in patients with PIVH. Methods: Patients admitted to Department of Neurosurgery, West China Hospital with PIVH between 2010 and 2016 were retrospectively included in our study. Clinical, radiographic, and laboratory data were collected. Univariate and multivariate logistic regression analyses were used to identify independent predictors of poor outcomes. Results: One hundred and seventy patients were included in the analysis. Mean admission blood glucose level was 7.78±2.73 mmol/L and 10 patients (5.9%) had a history of diabetes mellitus. History of diabetes mellitus (P = 0.01; Odds Ratio [OR], 9.10; 95% Confidence Interval [CI], 1.64 to 50.54) was independent predictor of admission critical hyperglycemia defined at 8.17 mmol/L. Patients with admission critical hyperglycemia poorer outcome at discharge (P < 0.001) and 90 days (P < 0.001). After adjustment, admission blood glucose was significantly associated with discharge (P = 0.01; OR, 1.30; 95% CI, 1.06 to 1.59) and 90-day poor outcomes (P = 0.03; OR, 1.27; 95% CI, 1.03 to 1.58), as well as mortality at 90 days (P = 0.005; OR, 1.41; 95% CI, 1.11 to 1.78). In addition, admission critical hyperglycemia showed significantly increased the incidence rate of pneumonia in PIVH (P = 0.02; OR, 6.04; 95% CI 1.27 to 28.80) even after adjusting for the confounders. Conclusion: Admission blood glucose after PIVH is associated with discharge and 90-day poor outcomes, as well as mortality at 90 days. Admission hyperglycemia significantly increases the incidence rate of pneumonia in PIVH.

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Do we Need Maintenance Chemotherapy in Advanced NSCLC in the Era of Immune and Targeted Therapy?

Current Cancer Therapy Reviews ◽

10.2174/1573394714666180417160205 ◽

2019 ◽

Vol 15 (1) ◽

pp. 50-55

Author(s):

Ahmed Nagy ◽

Omar Abdel Rahman ◽

Heba Abdullah ◽

Ahmed Negida

Keyword(s):

Lung Cancer ◽

Maintenance Therapy ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Statistical Significance ◽

Small Cell ◽

Maintenance Chemotherapy ◽

Small Cell Lung ◽

The Impact

Background: Although well established for the effective management of hematologic cancers, maintenance chemotherapy has only been recently incorportated as a treatment paradigm for advanced non–small-cell lung cancer. Maintenance chemotherapy aims to prolong a clinically favorable response state achieved after finishing induction therapy which is usually predefined in number before startng treatment. There are 2 modalities for maintenance therapy; continuation maintenance (involving a non-platinum component which was a part of the induction protocol or a targeted agent) and switch maintenance therapy (utilizing a new agent which was not a part of the induction regimen). Methods: The purpose of this article is to review the role of maintenance therapy in the treatment of advanced Non-Small Cell Lung Cancer (NSCLC) and provide a brief overview about induction chemotherapy in NSCLC to address the basis of maintenance therapy as a treatment option. We will also compare the impact of maintenance chemotherapy with the now evolving role of immunotherapy in NSCLC. Results: There have been 4 maintenance studies to date showing prolonged PFS and OS with statistical significance. However, Three out of the four studies (ECOG4599, JMEN, and PARAMOUNT) did not report tumor molecular analysis. As regard Immunotherapy, current data is in favour of strongly an increasing role for immunotherapy in NSCLC. Conclusion: Maintenance therapy in NSCLC continues to be an important therapeutic line to improve outcome in patients with metastatic and recurrent disease.

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The Impact of Translational Research in Breast Cancer Care: Can we Improve the Therapeutic Scenario?

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520617666171103105247 ◽

2018 ◽

Vol 18 (6) ◽

pp. 832-836

Author(s):

Giuseppe Buono ◽

Francesco Schettini ◽

Francesco Perri ◽

Grazia Arpino ◽

Roberto Bianco ◽

...

Keyword(s):

Breast Cancer ◽

Translational Research ◽

Cell Biology ◽

Cancer Biology ◽

Hormone Receptors ◽

Treatment Strategies ◽

Growth Factor Receptor ◽

Molecular Heterogeneity ◽

Therapeutic Implications ◽

The Impact

Traditionally, breast cancer (BC) is divided into different subtypes defined by immunohistochemistry (IHC) according to the expression of hormone receptors and overexpression/amplification of human epidermal growth factor receptor 2 (HER2), with crucial therapeutic implications. In the last few years, the definition of different BC molecular subgroups within the IHC-defined subtypes and the identification of the important role that molecular heterogeneity can play in tumor progression and treatment resistance have inspired the search for personalized therapeutic approaches. In this scenario, translational research represents a key strategy to apply knowledge from cancer biology to the clinical setting, through the study of all the tumors “omics”, including genomics, transcriptomics, proteomics, epigenomics, and metabolomics. Importantly, the introduction of new high-throughput technologies, such as next generation sequencing (NGS) for the study of cancer genome and transcriptome, greatly amplifies the potential and the applications of translational research in the oncology field. Moreover, the introduction of new experimental approaches, such as liquid biopsy, as well as new-concept clinical trials, such as biomarker-driven adaptive studies, may represent a turning point for BC translational research. </P><P> It is likely that translational research will have in the near future a significant impact on BC care, especially by giving us the possibility to dissect the complexity of tumor cell biology and develop new personalized treatment strategies.

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Treatment of HIV-associated facial lipoatrophy: impact on infection progression assessed by viral load and CD4 count

Anais Brasileiros de Dermatologia ◽

10.1590/abd1806-4841.2013895 ◽

2013 ◽

Vol 88 (4) ◽

pp. 570-577 ◽

Cited By ~ 5

Author(s):

Flávia Machado Gonçalves Soares ◽

Izelda Maria Carvalho Costa

Keyword(s):

Viral Load ◽

Disease Progression ◽

Statistical Significance ◽

Undetectable Viral Load ◽

Fat Distribution ◽

Cd4 Count ◽

Before And After ◽

Facial Lipoatrophy ◽

A Prospective Study ◽

The Impact

BACKGROUND: HIV/AIDS-Associated Lipodystrophy Syndrome includes changes in body fat distribution, with or without metabolic changes. The loss of fat from the face, called facial lipoatrophy, is one of the most stigmatizing signs of the syndrome.OBJECTIVES:To evaluate the effect of FL treatment using polymethylmethacrylate (PMMA) implants on disease progression, assessed by viral load and CD4 cell count.METHODS: This was a prospective study of 44 patients treated from July 2009 to December 2010. Male and female patients, aged over 18 years, with clinically detectable FL and who had never been treated were included in the study. PMMA implantation was done to fill atrophic areas. Laboratory tests were conducted to measure viral load and CD4 count before and after treatment.RESULTS: Of the 44 patients, 72.72% were male and 27.27% female, mean age of 44.38 years. Before treatment, 82% of patients had undetectable viral load, which increased to 88.6% after treatment, but without statistical significance (p = 0.67). CD4 count before treatment ranged from 209 to 1293, averaging 493.97. After treatment, the average increased to 548.61. The increase in CD4 count after treatment was statistically significant with p = 0.02.CONCLUSION: The treatment of FL with PMMA implants showed a statistically significant increase in CD4 count after treatment, revealing the impact of FL treatment on disease progression. Viral load before and after treatment did not vary significantly.

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Does Social Support Affect the Health of the Elderly in Rural China? A Meta-Analysis Approach

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16183471 ◽

2019 ◽

Vol 16 (18) ◽

pp. 3471 ◽

Cited By ~ 1

Author(s):

Natuya Zhuori ◽

Yu Cai ◽

Yan Yan ◽

Yu Cui ◽

Minjuan Zhao

Keyword(s):

Social Support ◽

Rural Areas ◽

Rural China ◽

Statistical Significance ◽

Empirical Studies ◽

Relevant Literature ◽

The Elderly ◽

Significant Difference ◽

Meta Regression ◽

The Impact

As the trend of aging in rural China has intensified, research on the factors affecting the health of the elderly in rural areas has become a hot issue. However, the conclusions of existing studies are inconsistent and even contradictory, making it difficult to form constructive policies with practical value. To explore the reasons for the inconsistent conclusions drawn by relevant research, in this paper we constructed a meta-regression database based on 65 pieces of relevant literature published in the past 25 years. For more valid samples to reduce publication bias, we also set the statistical significance of social support to the health of the elderly in rural areas as a dependent variable. Finally, combined with multi-dimensional social support and its implications for the health of the elderly, meta-regression analysis was carried out on the results of 171 empirical studies. The results show that (1) subjective support rather than objective support can have a significant impact on the health of the elderly in rural areas, and there is no significant difference between other dimensions of social support and objective support; (2) the health status of the elderly in rural areas in samples involving western regions is more sensitive to social support than that in samples not involving the western regions; (3) among the elderly in rural areas, social support for the older male elderly is more likely to improve their health than that for the younger female elderly; and (4) besides this, both data sources and econometric models greatly affect the heterogeneity of the effect of social support on the health of the elderly in rural areas, but neither the published year nor the journal is significant. Finally, relevant policies and follow-up studies on the impact of social support on the health of the elderly in rural areas are discussed.

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33 An Evidence Based Laser Therapy Algorithm for the Treatment of Burn Scars

Journal of Burn Care & Research ◽

10.1093/jbcr/irab032.037 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

pp. S26-S27

Author(s):

Rajiv Sood

Keyword(s):

Laser Treatment ◽

Laser Therapy ◽

Co2 Laser ◽

Statistical Significance ◽

Evidence Based ◽

Baseline Measurement ◽

Burn Scar ◽

Therapy Algorithm ◽

Laser Treatments ◽

The Impact

Abstract Introduction Hypertrophic scarring after burn injury can be extremely painful, cause profound itching, and affect the way patients view themselves and how the outside world perceives them. We have utilized laser therapy as a modality for scar modulation for our patients since 2013. In 2014, we initiated and completed a prospective IRB approved study to evaluate the outcome of scars treated with fractional CO2 laser therapy (FLT) utilizing objective and subjective tools. Recently, we have completed a prospective study evaluating the use of pulse dye laser (PDL) therapy and the impact on post-burn pruritis. In reviewing the outcomes from these two studies, we have developed an evidence-based laser therapy algorithm for burn scar management. Methods The FLT study entailed a series of three CO2 laser treatments minimally 4–6 weeks apart with scar measurements and POSAS form completion performed prior to each laser treatment and four weeks after the last FLT. Scar measurements that included color, pliability, and scar thickness; and completion of the POSAS form were obtained prior to each laser therapy session and four weeks after the third laser treatment. The measurements of color, pliability, and scar thickness were measured with the Colorimeter, Cutometer, and ultrasound. The PDL study utilized the 5-D Itch scale to evaluate post-burn pruritis. A baseline measurement was obtained prior to any laser treatments. Each patient underwent two PDL sessions and a 5-D itch scale was completed four to six weeks after the second PDL session. The baseline measurement was then compared to the final 5-D itch scale measurement. Results Data from the FLT study is in Table 1 and shows that there were statistically significant improvements in the Patient and Observer POSAS scores, patient rated Itch score, scar thickness, and measured skin density. Changes to patient rated scar pain, scar color, and pliability were noted but were not of statistical significance. Data from the PDL study is in Table 2 and shows a statistically significant decrease in the treated patients’ post-burn pruritis. Conclusions In reviewing the outcomes of these two studies, we have developed an algorithm based on our studies. All of our patients undergoing laser therapy receive two PDL sessions that are four to six weeks apart followed by 3 FLT sessions. The use of both PDL and FLT decreases post-burn pruritis, decreases scar thickness, decreases pain, and increases patient satisfaction as shown in our research.

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