tbuckley/cabot-search huggingface dataset:
The fine line between regional and metastatic pelvic lymph nodes in rectal cancer: Patterns of care among U.S. radiation oncologists.
Authors: Jehan Yahya, Daniel Herzig, Matthew Farrell, Catherine Degnin, Yiyi Chen, John M. Holland, Simon Brown, Jerry Jeff Jaboin, Vassiliki Liana Tsikitis, Kim Lu, Charles R. Thomas, Timur Mitin
Journal: Journal of Clinical Oncology (2018)

758 Background: Management of rectal cancer with involved lateral pelvic lymph nodes (LPLNs) at the time of diagnosis – the stage we refer institutionally to as Stage 3.5 – is controversial. Asian investigators consider internal, external and common iliac lymph nodes (LNs) as regional disease and treat these patients (pts) with curative intent, which often includes LPLN dissection. Conversely, AJCC 7 th edition classifies internal iliac LNs as regional, whereas both external and common iliac LNs as metastatic. NCCN guidelines recommend definitive trimodality therapy for Stage III rectal cancer, and palliative chemotherapy for Stage IV disease. Radiation oncologists (ROs) in the U.S. irradiate iliac LNs in the setting of other pelvic malignancies, but it is unknown how they approach newly diagnosed rectal cancer pts with LPLN involvement. Methods: We conducted an anonymous IRB-approved online survey of practicing U.S. ROs, probing their approach to management of rectal cancer pts with clinically involved LPLNs. Results: We received 220 responses. Among the responders, 85 are academically affiliated and the majority self-declared a specialization in treating GI malignancies, with 98 seeing more than 10 rectal cancer pts annually. Among respondents, 10.5% and 34.2% recommend biopsy of clinically involved internal and common iliac LNs, respectively. The vast majority of responders – 98.6% and 94.5% – treat involved internal and common iliac LNs with curative intent, respectively. Respondents recommend treatment intensification to involved internal iliac LNs by dissection of the nodal basin (88.2%) and radiation therapy (RT) boost (59.1%), and treatment intensification to involved common iliac LNs by LN dissection (76.4%) and RT boost (63.6%). Conclusions: Our analysis reveals that the vast majority of surveyed U.S. ROs approach pts with involved LPLNs, both regional (internal iliac) and metastatic (i.e. common iliac) with curative intent. They recommend treatment intensification with surgical resection and/or RT boost to involved nodes. Prospective clinical trials need to determine the appropriate management of pts with Stage 3.5 rectal cancer.
Abstract 10861: Administration of Non-Absorbable Antibiotics Attenuate High-Fat High-Cholesterol Diet Induced Atherosclerosis in LDLR-/- Mice
Authors: Siddhartha S Ghosh, Jinghua Bie, Jing Wang, Barbara Szomju, Shobha Ghosh
Journal: Circulation (2011)

Consumption of diets enriched in fat and cholesterol not only leads to obesity but is associated with chronic low grade inflammation. Diet induced changes in intestinal barrier function leading to bacterial translocation and/or release of lipopolysaccharide (LPS) to plasma contributes to increased inflammation. We hypothesized that administration of non-absorbable antibiotics such as Neomycin and Polymyxin-B should selectively decontaminate the gut, decrease high-fat high-cholesterol diet (HFHC) induced chronic inflammation and attenuate atherosclerosis, an inflammation linked disease. LDLR-/- mice at 8-weeks of age were fed HFHC diet with or without supplementation with Neomycin (100 mg/ml) and Polymyxin-B (10 mg/ml) in drinking water. After 16 weeks, mice were sacrificed. Plasma LPS levels were determined as a measure of diet-induced change in intestinal barrier function as well as inflammation. Antibiotic treatment significantly decreased plasma LPS concentration (2.18±0.89 vs 3.61±0.90 units/ml, P=0.013). Consistently, there was attenuation in the circulating levels of pro-inflammatory cytokines. Development of diet-induced atherosclerosis was assessed by en face analyses. Consistent with this model, there was significant lesion development in the aortic arch compared to thoracic and abdominal aorta (see Figure) which was dramatically reduced with antibiotic supplementation. Treatment with antibiotics significantly attenuated diet-induced atherosclerosis with a 43.9% decrease (3.00±1.16 vs 6.82±1.72, P=3.01E-06) in total lesion area and 45.6% decrease (11.34±4.38 vs 24.82±4.81, P=5.95E-07) in area occupied by lesions in the aortic arch. These data demonstrate that selective decontamination of the gut can significantly reduce the release of LPS into the plasma and systemic inflammation leading to attenuation of HFHC diet-induced atherosclerosis, thus establishing gut decontamination as a novel anti-atherogenic target.
Rare SOX9+CELLS behind MYC-Driven Medulloblastoma Recurrence
Authors: Sara Bolin, Vasil Savov, Anna Borgenvik, Alexandra Garancher, Gabriela Rosen, Aldwin Suryo Rahmanto, Sonja Hutter, Jessica Rusert, Grammatiki Fotaki, Rebecca Hill, Adrian Dubuc, Marc Remke, Matko Cancer, Vijay Ramaswamy, Steve Clifford, Olle Sangfelt, Ulrich Schueller, Michael Taylor, Robert Wechsler-Reya, Holger Weishaupt, Fredrik Swartling
Journal: Neuro-Oncology (2017)
Schistosoma mansoni Egg–Secreted Antigens Activate Hepatocellular Carcinoma–Associated Transcription Factors c‐Jun and STAT3 in Hamster and Human Hepatocytes
Authors: Martin Roderfeld, Sevinc Padem, Jakob Lichtenberger, Thomas Quack, Ralf Weiskirchen, Thomas Longerich, Gabriele Schramm, Yuri Churin, Karuna Irungbam, Annette Tschuschner, Anita Windhorst, Christoph G. Grevelding, Elke Roeb
Journal: Hepatology (2018)

Clinical data have provided evidence that schistosomiasis can promote hepatocellular carcinogenesis. c‐Jun and STAT3 are critical regulators of liver cancer development and progression. The aim of the present study was to investigate the hepatocellular activation of c‐Jun and STAT3 by Schistosoma mansoni infection. Expression and function of c‐Jun and STAT3 as well as proliferation and DNA repair were analyzed by western blotting, electrophoretic mobility‐shift assay, and immunohistochemistry in liver of S. mansoni –infected hamsters, Huh7 cells, primary hepatocytes, and human liver biopsies. Hepatocellular activation of c‐Jun was demonstrated by nuclear translocation of c‐Jun, enhanced phosphorylation (Ser73), and AP‐1/DNA‐binding in response to S. mansoni infection. Nuclear c‐Jun staining pattern around lodged eggs without ambient immune reaction, and directionally from granuloma to the central veins, suggested that substances released from schistosome eggs were responsible for the observed effects. In addition, hepatocytes with c‐Jun activation show cell activation and DNA double‐strand breaks. These findings from the hamster model were confirmed by analyses of human biopsies from patients with schistosomiasis. Cell culture experiments finally demonstrated that activation of c‐Jun and STAT3 as well as DNA repair were induced by an extract from schistosome eggs (soluble egg antigens) and culture supernatants of live schistosome egg (egg‐conditioned medium), and in particular by IPSE/alpha‐1, the major component secreted by live schistosome eggs. The permanent activation of hepatocellular carcinoma–associated proto‐oncogenes such as c‐Jun and associated transcription factors including STAT3 by substances released from tissue‐trapped schistosome eggs may be important factors contributing to the development of liver cancer in S. mansoni –infected patients. Therefore, identification and therapeutic targeting of the underlying pathways is a useful strategy to prevent schistosomiasis‐associated carcinogenesis.
A multidimensional overview of the burden of psoriasis
Authors: C.E.M. Griffiths, S.-J. Jo, L. Naldi, R. Romiti, E. Guevara-Sangines, T. Howe, G. Pietri, I. Gilloteau, C. Richardson, H. Tian, M. Augustin
Journal: British Journal of Dermatology (2018)

Psoriasis is a common, chronic, inflammatory skin disease which affects between 0.09% and 11.4% of the population worldwide. It causes symptoms such as itch and skin pain, but its effects can actually extend beyond the skin. It is often associated with additional co‐occurring diseases (comorbidities) such as cardiovascular disease, psoriatic arthritis (PsA), obesity, diabetes and anxiety or depression. Altogether psoriasis can cause significant negative impact on the quality of life (QoL) as well as work productivity of psoriasis patients. Additionally, the presence of common and bothersome symptoms such as itch and psoriasis lesions on different body areas can further increase the burden of disease on patients. In this large and multinational survey of dermatologists and their psoriasis patients, we estimated the incremental burden of comorbidities, itch, and affected body areas among patients with moderate to severe psoriasis. Anonymised responses were collected from 524 dermatologists and 3,821 psoriasis patients across 9 countries (UK, France, Germany, Spain, Italy, Russia, South Korea, Mexico and Brazil) using questionnaires and analysed to assess the impact of psoriasis on patients. Questionnaires collected data regarding psoriasis symptoms (presence/extent of itch, sleep disturbance due to itch, presence of skin pain), QoL and medical resource utilisation in the past 12 months (e.g. number of consultations that patients had with their dermatologist and number of hospitalisations). Overall, the results indicate that the presence of physical and psychological comorbidities, symptoms such as itch, presence of psoriasis lesions especially on visible (e.g. scalp, face, hands) and sensitive areas (e.g. genitals, scalp, face) significantly affect psoriasis patients’ QoL and cause significant financial burden due to work productivity impairment and increased usage of medical resources.
Feasibility of sentinel node biopsy in patients with locally advanced breast cancer after neoadjuvant therapy: A pilot study.
Authors: Ariadna Tibau Martorell, Joan Duch, Maria Jesus Quintana, Laura Lopez Vilaro, Belen Ojeda, M Carmen Alonso, Teresa Ramon y Cajal, Enrique Lerma, Antonio Moral, Enric Capdevila, Rosa Pineda, Josep Maria Sabate, Montserrat Estorch, Agust Barnadas
Journal: Journal of Clinical Oncology (2012)

1120 Background: Sentinel lymph node biopsy (SLNB) is a widely used staging method for patients with early breast cancer. Neoadjuvant Therapy (NT) modifies the anatomical conditions in the breast and axilla, and thus reliability of SLNB after NT remains controversial. The aim of this study is to prospectively evaluate the feasibility and accuracy of this procedure in this particular group of patients. Methods: Between December 2007-2011, 69 patients (mean age 56 years) with locally advanced breast cancer (LABC) were prospectively studied. Patients were T1-4, N0-1, M0. Prior to surgery, 61 patients received chemotherapy (CT) (adryamicin/cyclophosphamide followed by docetaxel) and 8 patients endocrine therapy (ET). Thirty nine patients were initially node-negative (cN0) and 30 patients had clinical/ultrasound node-positive confirmed by cytology (cN1) at presentation. All patients were clinical and ultrasound node-negative after NT. The study contained two groups of patients: group A (validation) included the first 29, associated with an axillary lymph node dissection (ALND) after NT, in order to validate the study, and group B included the last 40, only associated with an ALND when SLNB was positive or not found. Results: Whole SLNB identification rate was 89.9%, and no significant differences were found between patients initially cN0 (92%; 36/39) and initially cN1 (87%; 26/30). Four of 7 patients in whom SLNB was not found had residual nodal metastasis after NT (3 of them were initially cN1). Sentinel lymph nodes were successfully identified in 87% (7/8) of patients after ET and in 90% (55/61) of patients after CT. There was one false negative (FN) case after CT in group A (9% of overall false negative rate, initially cN0) and there were no FN cases after ET. Positive SLNB were higher in initially cN1 group (53%; 16/30) than in initially cN0 group (18%; 7/39). Conclusions: SLNB after NT (CT or ET) is safe and feasible in patients with LABC, not only in initially cN0 but also in initially cN1. It accurately predicts the status of the axilla and avoids unnecessary ALND.
Abiraterone Alone or in Combination With Enzalutamide in Metastatic Castration-Resistant Prostate Cancer With Rising Prostate-Specific Antigen During Enzalutamide Treatment
Authors: Gerhardt Attard, Michael Borre, Howard Gurney, Yohann Loriot, Corina Andresen-Daniil, Ranjith Kalleda, Trinh Pham, Mary-Ellen Taplin
Journal: Journal of Clinical Oncology (2018)

Purpose Enzalutamide resistance could result from raised androgens and be overcome by combination with abiraterone acetate. PLATO ( ClinicalTrials.gov identifier: NCT01995513) interrogated this hypothesis using a randomized, double-blind, placebo-controlled design. Patients and Methods In period one, men with chemotherapy-naïve metastatic castration-resistant prostate cancer received open-label enzalutamide 160 mg daily. Men with no prostate-specific antigen (PSA) increase at weeks 13 and 21 were treated until PSA progression (≥ 25% increase and ≥ 2 ng/mL above nadir), then randomly assigned at a one-to-one ratio in period two to abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily with either enzalutamide or placebo (combination or control group, respectively) until disease progression as defined by the primary end point: progression-free survival (radiographic or unequivocal clinical progression or death during study). Secondary end points included time to PSA progression and PSA response in period two. Results Of 509 patients enrolled in period one, 251 were randomly assigned in period two. Median progression-free survival was 5.7 months in the combination group and 5.6 months in the control group (hazard ratio, 0.83; 95% CI, 0.61 to 1.12; P = .22). There was no difference in the secondary end points. Grade 3 hypertension (10% v 2%) and increased ALT (6% v 2%) or AST (2% v 0%) were more frequent in the combination than the control group. Conclusion Combining enzalutamide with abiraterone acetate and prednisone is not indicated after PSA progression during treatment with enzalutamide alone; hypertension and elevated liver enzymes are more frequent with combination therapy.
Abstract 15382: Engineering the Adventitia to Build a Better Vascular Graft
Authors: Mai T Lam, Cameron Pinnock, Bijal Patel
Journal: Circulation (2016)

Introduction:  To treat atherosclerosis, a patient’s own blood vessels are harvested for bypass surgery, creating further injury. Engineered vessels could save patients from undue harm. The outer layer of a blood vessel, or adventitia, provides strength. In most engineered vessels, a polymer tube is used to approximate the role of the adventitia. However, polymer grafts have proven issues with patency. Our hypothesis is that a completely cellular adventitia will decrease immune response and improve patency.   Methods:  To generate a cellular adventitia, we used our recently developed method for creating rings of tissue which are then stacked to form a tubular, vascular structure. Human dermal fibroblasts were plated into a culture dish with a center plastic post. Cell attachment was controlled using a hydrogel substrate. Once the cell monolayer forms, it detaches and aggregates around the center post forming a ring. To strengthen the rings, ascorbic acid and/or TGF-beta were added. Both factors stimulate production of collagen and elastin, proteins governing strength and elasticity of blood vessels.   Results:  Ascorbic acid produced thin rings (~157 um). TGF-beta produced thicker rings (~483 um), though lacked structure. The addition of both ascorbic acid and TGF-beta resulted in the most stable rings (~386 um). PCR analysis showed that collagen and elastin production was increased with either factor, and highest when combined. Ascorbic acid resulted in the highest amount of elastin expression, demonstrated in the structure of these rings. TGF-beta increased collagen production, however elastin was low, evidenced by lower expression of elastin and loose rings. Stimulation by both factors produced thick, tight rings indicative of the adventitia.   Conclusions:  This work shows that a completely cellular tunica adventitia can be engineered. Through our continued work on strengthening our engineered adventitia, engineered vascular grafts could become more functional.
Abstract 20062: Endothelial Smad4 Contributes to Beiging of White Adipose Tissue by Regulating Angiogenesis and Adipogenic Precursor Proliferation
Authors: Xiao Yu Tian, Hongsong Zhang, Chenguang Wang, Mingyu Huo, Ronald C Ma, Yu Huang
Journal: Circulation (2017)

Introduction: Cold stress increases adrenergic stimulation of white adipose tissue (WAT) by upregulating uncoupling protein 1 (UCP1) to transform WAT into a brown adipose tissue -like phenotype, or...
Missed opportunity? Worsening breathlessness as a harbinger of death: a cohort study
Authors: David C. Currow, Joanna M. Smith, Phichai Chansriwong, Simon I.R. Noble, Theodora Nikolaidou, Diana Ferreira, Miriam J. Johnson, Magnus Ekström
Journal: European Respiratory Journal (2018)

The aim of the study was to explore trajectories of breathlessness intensity by function and life-limiting illness diagnosis in the last 3 weeks of life in palliative care patients. A prospective, consecutive cohort study obtained point-of-care data of patients of Silver Chain Hospice Care Service (Perth, Australia) over the period 2011–2014 (n=6801; 51 494 data-points). Breathlessness intensity (0–10 numerical rating scale) and physical function (Australia-modified Karnofsky Performance Status (AKPS)) were measured at each visit. Time was anchored at death. Breathlessness trajectory was analysed by physical function and diagnosis using mixed effects regression. Mean± sd age was 71.5±15.1 years and 55.2% were male, most with cancer. The last recorded AKPS was &gt;40 for 26.8%. Breathlessness was worst in people with cardiorespiratory disease and AKPS &gt;40, and breathlessness in the last week of life increased most in this group (adjusted mean 2.92 versus all others 1.51; p=0.0001). The only significant interaction was with diagnosis and function in the last week of life (p&lt;0.0001). Breathlessness is more intense and increases more in people with better function and cardiorespiratory disease immediately before death. Whether there are reversible causes for these people should be explored prospectively. Omitting function from previous population estimates may have overestimated breathlessness intensity for many patients in the days preceding death.
Future directions for reducing inequity and maximising impact of child health strategies
Authors: Sarah L Dalglish, Joanna J Vogel, Geneviève Begkoyian, Luis Huicho, Elizabeth Mason, Elisabeth Dowling Root, Joanna Schellenberg, Abiy Seifu Estifanos, Rajani Ved, Fernando C Wehrmeister, Guilhem Labadie, Cesar G Victora
Journal: BMJ (2018)

Current global child health strategies have reduced wealth based inequities in care seeking for childhood illness, but we need much greater emphasis on equity in strategy design and implementation, say <b>Sarah L Dalglish and colleagues</b>
Caffeine Supplement Warning
Authors: Rebecca Voelker
Journal: JAMA (2018)

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Association between inflammatory bowel disease and Parkinson’s disease: seek and you shall find?
Authors: Petra Weimers, Jonas Halfvarson, Michael C Sachs, Jonas F Ludvigsson, Inga Peter, Ola Olén, Johan Burisch
Journal: Gut (2018)

We read with great interest the article by Villumsen et al 1 about the association between inflammatory bowel disease (IBD) and Parkinson’s disease (PD). Villumsen et al estimated the risk of developing PD to be 22% higher in a Danish IBD population than in a non-IBD population.

During the last decade, evidence has accumulated that shared biological mechanisms are involved in the development of IBD and PD.2 However, the clinical co-occurrence of IBD and PD has only been investigated to a limited extent and with inconsistent results.3–5 Thus, concerns have been raised about how best to interpret this possible association.

In a recently published article by our group, we too demonstrated a positive association between PD and IBD.6 We observed that Swedish patients with IBD were at 30% higher risk of subsequently developing PD than were non-IBD individuals. Furthermore, that patients with IBD had higher …
Prognostic Value of FDG-PET/CT Metabolic Parameters in Metastatic Radioiodine-Refractory Differentiated Thyroid Cancer
Authors: Poorni M. Manohar, Lauren J. Beesley, Emily L. Bellile, Francis P. Worden, Anca M. Avram
Journal: Clinical Nuclear Medicine (2018)

Purpose There are no standardized prognostication algorithms for metastatic radioiodine-refractory (RAI-R) differentiated thyroid cancer (DTC). We hypothesize that [ 18 F]-FDG PET/CT may predict progression versus stability of disease based on quantitative analysis of metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Methods Retrospective study of 62 patients with metastatic RAI-R DTC to determine clinical outcomes with median follow-up from initial diagnosis of 11.1 years (8.38, 14.1) (range, 1.2–20 years). Baseline [ 18 F]-FDG PET/CT scans were evaluated qualitatively for regional and distant metastases and quantitatively for tumor burden based on MTV and TLG obtained using gradient segmentation method. Results After diagnosis of metastatic RAI-R disease was established, the 5-year overall survival (OS) probability was 34%, and median OS was 3.56 years (2.87, infinity). The 5-year progression-free survival (PFS) probability was 19%, and median PFS was 1.31 years (1.03, 2.38). TSH-suppressed thyroglobulin (Tg) levels greater than 100 ng/mL and Tg doubling time (Tg-DT) less than 6 months were significantly associated with worse OS and PFS. Higher than median values of MTV and TLG were associated with worse OS ( P = 0.06) and PFS ( P = 0.007). Higher hazard of death was noted for higher values of log-MTV and log-TLG (HR, 1.17 [95% confidence interval, 0.99–1.39], P = 0.05, and HR, 1.14 [95% confidence interval, 1.00–1.31], P = 0.05, respectively). Conclusions [ 18 F]-FDG PET/CT metabolic parameters can help define the volume and biologic variations of metastatic tumor burden. Metabolic tumor volume and TLG can be used for dynamic risk stratification of patients with metastatic RAI-R DTC regarding PFS and complement Tg-DT for prognosis of clinical disease course.