tbuckley/cabot-search huggingface dataset:
The retrospective analysis of central nervous system lymphomas: Single-center experience.
Authors: Veli Sunar, Arzu Yasar, Furkan Sarici, Ece Esin, Omer Diker, Sahin Lacin, Alev Turker, Evren Ozdemir, Ibrahim Barista, Ayse Kars
Journal: Journal of Clinical Oncology (2015)

e13053 Background: Primary central nervous system lymphomas (PCNSL) account for 5% of all central nervous system tumors and 1% of all lymphoma cases. Due to the increase in congenital and acquired immune deficiency syndromes in the last 20 years, an increase in incidence of PCNSL has been observed. Histologically 90% of the cases are agressive B cell lymphomas, and the most common histopathologic subtype among these is the diffuse large B cell lymphoma. In this study, we aimed to evaluate the treatment outcomes of the patients with PCNSL who were diagnosed between 2000-2013 in our center, retrospectively. Methods: Thirty one patients with PCNSL whose median age was 56, were included in the study. The demographic characteristics and the treatment strategies were analyzed retrospectively. The overall survival and the progression free survival were calculated by the Kaplan Meier statistical method Results: A total of 31 patients with PCNSL were included in the study. All of the patients had the histopathologic subtype of diffuse large B cell lymphoma. Of the patients, 70.1% were male (n = 22), while 29.1% (n = 9) were female. The ECOG performance status was 1 in 54.8 % (n = 17), 2 in 38.8% (n:12) and 3 in 6.4% (n:2). The first line therapy was high dose methotrexate in 64.5% (n:20) of patients, radiotherapy in 29% (n:9), R-CHOP chemotherapy in 6.5% (n:2), and concomitant intrathecal treatment in 6% (n:2). When the response to treatment was analyzed; 19.3% (n:6) of the patients had complete response, 32.2% (n:10) had partial response, and 19.3% (n:6) had progressive disease. In the second line therapy, 22% (n:7) of the patients were administered radiotherapy, 3% (n:1) had high dose ARA-C, and 3% (n:1) had cyber-knife treatment. The median PFS was 5.2 months while median OS was 8.6 months. Conclusions: PCNSL is an extranodal lymphoma with agressive clinical course. The median survival is approximately 20 months with treatment modalities such as chemotherapy and radiotherapy. The PFS and OS were found to be lower than the literature in our series. Despite the current treatment modalities, the patients in our series had more agressive clinical course.
Abstract MP61: Preterm Delivery and Patterns of Cardiometabolic Risk Factors Pre- and Post-Childbearing: Coronary Artery Risk Development in Young Adults Study
Authors: Baiyang Sun, Marnie Bertolet, Cora E Lewis, Erica P Gunderson, Janet M Catov
Journal: Circulation (2019)

Introduction: Women with preterm delivery (PTD) have excess CVD risk and unfavorable risk factors before, during and after pregnancy, but few studies compare the pre- and post-childbearing eras. Hypothesis: Women with PTD have worse patterns of CVD risk factors both pre- and post-childbearing. Methods: CARDIA is a multi-center 30-year longitudinal (9 exams, 1985-2016) cohort of black and white adults initially aged 18-30. We included women with ≥1 post-baseline birth (n=1298) and categorized them according to PTD (any birth &lt;37 wks.) or term births (all births ≥37 wks.). Annual changes in CVD risk factor (BMI, waist girth, lipids, and blood pressure [BP]) during pre-childbearing period (before the first post-baseline birth) and post-childbearing period (after the last post-baseline birth) were compared between PTD and term groups, using piecewise linear mixed-models which allowed differing intercepts and slopes for pre- and post-childbearing eras. Intercepts were set at the end of pre-childbearing and the start of post-childbearing; childbearing period, from the first to the last post-baseline birth, was collapsed. Models adjusted for socioeconomics, length of childbearing period, parity, time-varying lifestyle habits and medication use. Results: The annual BMI increase during the pre-childbearing period did not differ by group, but the annual BMI increase after childbearing was larger in PTD group than term group (0.22 vs. 0.18 kg/m 2 , p=0.04; Table). The difference in diastolic BP from before to after childbearing period in PTD group was larger than term group (2.77 mmHg, p&lt;0.01), with similar pre- and post-childbearing annual change in each group. No other risk factor differences were found. Conclusions: PTD was not associated with pre-childbearing changes in CVD risk factors, but women with PTD exhibited accelerated gains of adiposity during the post-childbearing period, and worse diastolic BP pattern when completing childbearing. Further research is needed to assess the changes during childbearing period.
To Give or Not to Give Prophylactic Antibiotics for Miscarriage Surgery?
Authors: David M. Serwadda
Journal: New England Journal of Medicine (2019)

Although data are limited, spontaneous abortion has been reported in as many as a fifth of pregnancies in some populations in low- and medium-income countries (LMICs).1 Miscarriages rates are noted to be higher among women who are positive for human immunodeficiency virus (HIV) infection than among those who are HIV-negative,2 and HIV prevalence rates are particularly high among women of childbearing age in east and southern Africa. Miscarriages are associated with high morbidity and mortality, mainly due to infections or hemorrhage. Surgery is frequently used to manage incomplete miscarriage in LMICs, and it is a common practice to prescribe prophylactic . . .
Early Engraftment of Unrelated Cord Blood Transplantation in Patients with Acquired Severe Aplastic Anemia Using Conditioning Regimen without Anti-Thymocyte Globulin
Authors: Wan Xiang, Huilan Liu, Baolin Tang, Xiaoyu Zhu, Yao Wen, Lei Zhang, Kaidi Song, Xuhan Zhang, Guangyu Sun, Zimin Sun
Journal: Blood (2018)
Geographic variations of clinical characteristics in breast cancer: Analysis of Turkish National Breast Cancer Registry.
Authors: Saadettin Kilickap, Kadri Altundag, Esra Dumanli, Mahmut Gumus, Ruchan Uslu, Ozgur Ozyilkan, Bulent Yalcin, Oguz Kara, Gamze Gokoz Dogu, Banu Ozturk, Ali Osman Kaya, Mehmet Aliustaoglu, Dogan Uncu, Feyyaz Ozdemir, Irfan Cicin, Metin Ozkan, Murat Kocer, Hande Turna, Suleyman Buyukberber, Mustafa Benekli
Journal: Journal of Clinical Oncology (2015)

e12656 Background: Breast cancer (BC) is the most common cancer in women in Turkey. Presumed differences in patterns of BC presentation in pts from various geographical regions of Turkey have not been studied. We aimed to define differences in clinical and pathological variables in Turkish women according to geographical distribution. Methods: BC pts presenting to medical oncology clinics were prospectively registered after October 2012 in 28 centers. The effect of geographical distribution on the cinical and pathological characteristics of BC were analyzed. Results: 13749 pts were registered from the Eastern (33.1%) and the Western (66.9%) Turkey. Patients from 6 different regions were separately analyzed. Mean ages of Eastern pts were statistically lower than the Western pts (52.0±11.2 vs 54.0±11.5; p < 0.001). Male BC rate were twice as much in Eastern Turkey (1.3% vs 0.7%, p < 0.001). More patients were premenopausal in Eastern provinces (50.5 vs 45.1%, p < 0.001) with younger ages at diagnosis ( < 35 yrs: 5.1% vs 3.8% and > 75 yrs 2.7% vs 4.8%, p < 0.001 and p = 0.002, respectively). Patients in the Eastern Turkey were diagnosed in later stages (stage III: 30.8% vs 23.7% and stage IV: 9.4% vs 5.1%, respectively) (p < 0.001) (Figure 1). Patients living in Eastern Turkey had higher rates of ER-negative (p < 0.001), PR-negative (p < 0.001) and HER2-positive (p < 0.001) tumors (Table 1). Distribution of histological type and molecular subtypes were similar in both regions. Eastern patients were more obese (41.6 vs 36.1%, p < 0.001). Conclusions: BC patients from Eastern provinces of Turkey present at an earlier age with more advanced disease. These findings may partly be explained with ease of access to health care, but differences in ER, PR and Her2 status are intriguing in terms of genetic background of these patients.
Abstract P181: Young Adult Risk Factor Burden and Sleep Hypertension in Middle-Age: the Coronary Artery Risk Development in Young Adults Study
Authors: John N Booth, Joseph Schwartz, Norrina Allen, Bryron Jaeger, Cora Lewis, James Shikany, Yuichiro Yano, YiYi Zhang, Daichi Shimbo, Paul Muntner, Andrew Moran
Journal: Circulation (2019)

Introduction: Developing cardiovascular disease (CVD) risk factors at younger ages increases the risk for clinic hypertension. Few data report if earlier exposure to CVD risk factors impacts blood pressure (BP) during sleep. Hypothesis: Test whether exposure to CVD risk factors in young adulthood predicts sleep systolic BP (SBP) and sleep hypertension status in middle age, independent of risk factor levels in middle age. Methods: In 1985-86, the Coronary Artery Risk Development in Young Adults study enrolled 5115 adults 18-30 years old. CVD risk factors (i.e., body mass index [BMI], fasting glucose, cigarette smoking, alcohol intake, albumin to creatinine ratio [ACR] and estimated glomerular filtration rate [eGFR]) were measured at nine exams over 30 years. We analyzed 781 adults with a complete 24 hour ambulatory BP monitoring (ABPM) recording in year 30 at 48-60 years old. Sleep hypertension was defined as asleep SBP ≥ 120 mm Hg or diastolic BP (DBP) ≥ 70 mm Hg on ABPM. To assess the importance of earlier exposure to CVD risk factors on sleep SBP in middle age, a likelihood ratio test was used to compare nested multivariable adjusted linear regression models with CVD risk factors measured at all exams (Model 1) and year 30 only (Model 2). Poisson regression was used for the sleep hypertension outcome. Results: In year 30, the mean sleep SBP / DBP was 113 / 67 mm Hg; 41.1% of adults had sleep hypertension. Compared with CVD risk factors measured at year 30 only (Model 2), BMI, fasting glucose, cigarette smoking, alcohol intake, ACR and eGFR measured at all exams (Model 1) statistically significantly increased the explanatory value for higher sleep SBP in middle age (all p-values &lt; 0.05; Table ). With the exception of ACR (p=0.057), results were consistent for sleep hypertension. Conclusion: Exposure to less healthy levels of CVD risk factors in young adulthood may independently contribute to higher sleep SBP and having sleep hypertension by middle age. Studies with repeated ABPM are needed to track determinants of higher sleep BP over the lifespan.
Human Interleukin-34 facilitates microglia-like cell differentiation and persistent HIV-1 infection in humanized mice
Authors: Saumi Mathews, Amanda Branch Woods, Ikumi Katano, Edward Makarov, Midhun B. Thomas, Howard E. Gendelman, Larisa Y. Poluektova, Mamoru Ito, Santhi Gorantla
Journal: Molecular Neurodegeneration (2019)

Microglia are the principal innate immune defense cells of the centeral nervous system (CNS) and the target of the human immunodeficiency virus type one (HIV-1). A complete understanding of human microglial biology and function requires the cell's presence in a brain microenvironment. Lack of relevant animal models thus far has also precluded studies of HIV-1 infection. Productive viral infection in brain occurs only in human myeloid linage microglia and perivascular macrophages and requires cells present throughout the brain. Once infected, however, microglia become immune competent serving as sources of cellular neurotoxic factors leading to disrupted brain homeostasis and neurodegeneration. Herein, we created a humanized bone-marrow chimera producing human "microglia like" cells in NOD.Cg-PrkdcscidIl2rgtm1SugTg(CMV-IL34)1/Jic mice. Newborn mice were engrafted intrahepatically with umbilical cord blood derived CD34+ hematopoietic stem progenitor cells (HSPC). After 3 months of stable engraftment, animals were infected with HIV-1ADA, a myeloid-specific tropic viral isolate. Virologic, immune and brain immunohistology were performed on blood, peripheral lymphoid tissues, and brain. Human interleukin-34 under the control of the cytomegalovirus promoter inserted in NSG mouse strain drove brain reconstitution of HSPC derived peripheral macrophages into microglial-like cells. These human cells expressed canonical human microglial cell markers that included CD14, CD68, CD163, CD11b, ITGB2, CX3CR1, CSFR1, TREM2 and P2RY12. Prior restriction to HIV-1 infection in the rodent brain rested on an inability to reconstitute human microglia. Thus, the natural emergence of these cells from ingressed peripheral macrophages to the brain could allow, for the first time, the study of a CNS viral reservoir. To this end we monitored HIV-1 infection in a rodent brain. Viral RNA and HIV-1p24 antigens were readily observed in infected brain tissues. Deep RNA sequencing of these infected mice and differential expression analysis revealed human-specific molecular signatures representative of antiviral and neuroinflammatory responses. This humanized microglia mouse reflected human HIV-1 infection in its known principal reservoir and showed the development of disease-specific innate immune inflammatory and neurotoxic responses mirroring what can occur in an infected human brain.
Projecting the impact of treatment advances on the mortality results of mammography screening trials.
Authors: Jeanette Birnbaum, Vijayakrishna K. Gadi, Elan Markowitz, Ruth Douglas Etzioni
Journal: Journal of Clinical Oncology (2015)

e12626 Background: Screening trials are widely regarded as providing the highest level of evidence for screening policy development. However, the most cited breast screening trials were conducted decades ago. Since this time, treatment advances for breast cancer have improved disease-specific survival. Our objective was to examine whether treatment advances may have affected the mortality benefits of mammography screening. Methods: We used microsimulation modeling to project results of mammography trials under historic or contemporary systemic treatments. The virtual trials reflected a 15% reduction in advanced disease on the screen arm based on published results. Three treatment settings were considered: (1) historical, corresponding to the late 1970s (adjuvant chemotherapy among only a minority of late-stage cases), (2) updated, corresponding to the late 1990s (adjuvant chemotherapy for early- and late-stage cases and tamoxifen for ER+ cases), and (3) perfect, corresponding to optimal use of available contemporary treatments including aromatase inhibitors. Relative treatment benefits were assumed to be similar for women with localized and advanced disease. In the absence of screening or systemic treatment, disease-specific survival by stage was based on data for cases in the SEER registry diagnosed from 1975 to 1979. Absolute and relative breast cancer mortality reductions were projected over 13 and 25 years. Results: Projected mortality reductions over 13 years were similar across the three trial settings, with absolute reductions of 0.7, 0.6, and 0.5 per 1,000 women screened in the historical, updated, and perfect trials and corresponding relative reductions of 10%, 10%, and 11%. Mortality reductions declined more markedly across trials when treatment benefit was greater among advanced cases. Conclusions: Despite treatment advances, screening still confers relative and absolute mortality reductions similar to those in published screening trials. This study informs contemporary guidelines for breast cancer screening and can serve as a prototype in other cancer screening settings.
U.S. treatment patterns and healthcare resource use (HCRU) for stage IVC squamous cell carcinoma of the head and neck (SCCHN).
Authors: Daniel Mordecai Gilden, Joanna M. Kubisiak, Meredith J. Chace, Lee Bowman, Emily Nash Smyth, Li Li, Emily Kubisiak, David Ethan Gilden
Journal: Journal of Clinical Oncology (2015)

e17010 Background: Few publications have characterized treatment patterns beyond first-line therapy for patients with metastatic, (Stage IVC) SCCHN. Methods: Surveillance, Epidemiology and End Results (SEER) data (2005-2009) linked with Medicare claims (2002-2010) were used to characterize treatments and HCRU. Fee-for-service Medicare records were evaluated for : 1) ICD-O-3 site codes within 0-10 or 37-38 absent other primary cancer; 2) histology codes within 8050-8052, 8070-8078, or 8082-8084; and 3) initial Stage IVC diagnosis or metastatic diagnoses in secondary sites including liver, lung, bone, and brain. Lines of therapy were determined using rules sensitive to regimen transitions and gaps in systemic treatment. JEN Frailty Index and Charlson Comorbidity Index estimated functional and comorbid covariates, respectively. Survival was analyzed by Kaplan-Meier method and other time to events were described by median or mean with standard deviation. Results: This study identified 4,616 SCCHN cases, 68.6% male, and 8.7% were diagnosed with Stage IVC at initial presentation. Median survival was 18 months after detection of distant metastasis (95% CI: 16-19). Initial diagnosis of Stage IVC and high baseline functional impairment/comorbidity greatly increased mortality risk. First-line systemic therapy was received by 41.2% of patients, 10.5% received second-line and 3.4% third-line; cetuximab was the most common systemic therapy across all lines of therapy. 60.4% and 40.1% of patients received radiation therapy and surgery, respectively. The mean time from detection of distant metastases to start of therapy was 2.8 months (SD: 5.5) for first-line, 9.2 months (SD: 8.7) for second-line and 14.9 months (SD: 9.6) for third-line. Acute care hospitalizations, and visits to outpatient clinics, general practitioners and specialty physicians were the primary sources of HCRU over 15 months median follow-up. Conclusions: Examining SEER-Medicare records reveals the treatment/HCRU patterns of patients diagnosed with metastatic SCCHN. This new information shows the impact of successive systemic therapy lines. It establishes benchmarks for clinical evaluation and treatment.
Molecular and imaging correlates of exceptional pathologic response to neoadjuvant ADT plus enzalutamide.
Authors: Adam G. Sowalsky, Scott Wilkinson, Huihui Ye, Stephanie Harmon, Baris Turkbey, Nicole Carrabba, Rayann Atway, Guinevere Chun, David James VanderWeele, Fatima Karzai, Ravi Amrit Madan, Peter A. Pinto, Peter L. Choyke, William L. Dahut
Journal: Journal of Clinical Oncology (2019)

61 Background: AR directed therapies are standard of care for metastatic prostate cancer, and their use for high-risk localized disease may improve survival. Previous trials showed that suppression of AR activity resulting in greater pathologic responses improved survival rates. However, the underlying biology and molecular features of exceptionally responding tumors remain unknown. Methods: Men with locally advanced prostate cancer (median Gleason score 8, median PSA 9.58 ng/dl) received mpMRI and MRI/US-fusion targeted biopsies at baseline. Patients received 6 months of ADT plus enzalutamide, then received a second mpMRI, and underwent radical prostatectomy. RP specimens were whole mounted in the same plane as MRI. The location of each tumor on biopsy was mapped to prostatectomy specimens using pathologic and imaging hallmarks. FFPE sections of baseline and post-treatment tumor were stained, laser capture microdissected, and analyzed using whole exome sequencing. Amongst nonresponding patients (residual tumor burden &gt; 0.05 cc) comparison of pre- and post-treatment tumor specimens identified evolutionary phylogenies over space and time representing intrinsic or clonal selection of pre-existing cells. Amongst responding patients, clonal extinction was confirmed by sequencing and immunostaining of surgical specimens. Results: Gleason score at baseline did not differentiate responding and nonresponding patients. Focal ERG staining in biopsies was absent in 100% of responders and present in 60% of responders. Intraductal carcinoma architecture was also absent in all responding tumors. Focal PTEN loss was observed in all nonresponders at baseline. Responding tumor foci were enriched for deletion of chromosome 6q. Comparison of baseline mpMRI sequences indicated a trend towards lower variance on dynamic contract enhanced (DCE) MR and lower local texture heterogeneity metrics in responding lesions. Conclusions: Response to neoadjuvant intense ADT correlates with distinctive pathologic, molecular, and imaging features that can be observed prior to treatment. Selection of patients based on these parameters may improve overall responses to treatment in subsequent clinical trials. Clinical trial information: NCT02430480.
Abstract P221: Diet Quality and Incidence of Coronary Heart Disease and Coronary Revascularization Among US Women and Men With Hypertension
Authors: Sara Raposo, Ambika Satija, John Forman, Shanshan Li, Kenneth Mukamal, Marie Lof, JoAnn Manson, Frank Hu, Eric Rimm
Journal: Circulation (2019)

Background: Hypertension affects 45% of American adults and is a major risk factor for cardiovascular disease. Regrettably, about less than half of all affected individuals have their hypertension controlled. Healthy dietary patterns have been associated with a lower risk of cardiovascular disease in the general population. However, less is known about this association among individuals with hypertension. Aim: To study four diet quality scores, the alternate Mediterranean Diet (aMED) score; the alternate Healthy Eating Index 2010 (aHEI-2010); the Dietary Approaches to Stop Hypertension (DASH) score; and a Healthful Plant-based Diet Index (hPDI) and the incidence of coronary heart disease (CHD) and coronary revascularization (bypass, angioplasty or stent) among US women and men with hypertension. Methods: We included 22,270 women from the Nurses’ Health Study and 9,846 men from the Health Professionals Follow-up Study that had reported a professionally-diagnosed incident hypertension in 1988 or on subsequent biennial questionnaires. At inclusion, participants were free of other chronic diseases (CHD, coronary artery bypass/angioplasty/stent, angina, other heart disease, stroke, diabetes and cancer). Dietary data were collected every 4 years using a validated semi-quantitative food frequency questionnaire and covariate data were collected biennially. Using the cumulative average of dietary intake after hypertension diagnosis, we calculated hazard ratios (HR, 95% CI) comparing quintiles 5 to 1 of each diet quality score with multivariable Cox proportional hazards regression while adjusting for age, energy intake, alcohol (DASH and hPDI only), margarine (hPDI only), smoking, BMI, physical activity, family history of CHD, lipid-lowering medication, NSAIDs, postmenopausal hormone use (women) and hypertension medication. Results: We documented 922 incident CHD cases (299,520 person-years) and 1845 incident coronary revascularization cases (298,463 person-years) during follow-up. In pooled multivariable analyses, high adherence to all diet quality scores was inversely associated with risk of CHD (aMED: 0.73, 95% CI 0.59-0.91, p trend: &lt;0.01; aHEI-2010: 0.66, 95% CI 0.53-0.82, p trend: &lt;0.0001; DASH: 0.65, 95% CI 0.52-0.83, p trend: &lt;0.0001; hPDI: 0.78, 95% CI 0.61-0.99, p trend: 0.01) and coronary revascularization (aMED: 0.83, 95% CI 0.71-0.96, p trend: 0.02; aHEI-2010: 0.80, 95% CI 0.69-0.94, p trend: &lt;0.001; DASH: 0.88, 95% CI 0.75-1.03, p trend: 0.10; hPDI: 0.81, 95% CI 0.69-0.96, p trend: 0.07). Conclusions: This study suggests that individuals with hypertension may experience a lower risk of CHD and coronary revascularization with high adherence to healthy dietary patterns. Promoting healthy dietary habits among individuals with hypertension could be a cost-efficient and safe way to prevent the incidence of CHD and coronary revascularization.