tbuckley/cabot-search huggingface dataset:
TMPRSS-ERG fusion in men with prostate cancer (PCa) and non-prostate malignancies: Defining a role for comprehensive genomic profiling (CGP) to guide clinical care.
Authors: Primo Lara, Andreas Heilmann, Julia Andrea Elvin, Ralph deVere White, Regina Gandour-Edwards, Christopher P. Evans, Chong-xian Pan, Jeffrey S. Ross, Philip J. Stephens, Vincent A. Miller, Siraj Mahamed Ali
Journal: Journal of Clinical Oncology (2016)

5037 Background: Genomic rearrangements involving androgen-regulated TMPRSS & the ETS transcription factor ERG are found in ~50% of PCa tumors. Thus identification of TMPRSS-ERG is taken as a marker of prostatic origin. We assessed TMPRSS-ERG in a large series of genomic profiles of patients with various advanced cancers, including PCa and other malignancies. Methods: CGP of 315 cancer genes was applied to 50ng of DNA from submitted cases to assess all classes of genomic alterations. TMPRSS-ERG frequency across histologic subtypes was determined. CGP data from an index case of PCa with histologic evolution from adeno- to pure squamous cell cancer (SCC) is described. Results: TMPRSS-ERG was identified in 288 of 5,149 tumors in men; it was not detected in tumors from females. PCa accounted for 250 cases. Frequency by tumor type is shown. The index case is a patient with Gleason 9 PCa s/p surgery and radiation who developed a large left retrovesical mass pathologically proven to be pure SCC. TMPRSS-ERG was detected by CGP in the SCC tumor, primary PCa, and metachronous PCa metastasis. The patient is benefiting from androgen deprivation. Phylogenetic trees showing clonal and histopathologic evolution of PCa will be presented. Conclusions: In this large CGP dataset, TMPRSS-ERG fusion was seen in ~30% of PCa regardless of histologic type but was rarely detected in non-PCa tumors occurring in men. CGP can identify TMPRSS-ERG in PCa presenting as variant histology. As TMPRSS-ERG is almost exclusively associated with PCa, CGP should be considered in appropriate cases of metastatic cancer in men where the anatomic site of origin is uncertain as there are potential therapeutic implications. Subtype # of male patients # harboring TMPRSS-ERG % Prostate acinar ADC 715 214 30 Prostate NE Ca 51 18 35 Prostate Ca, undiff'd 40 11 28 Prostate ductal ADC 19 7 37 Undiff NE Ca of UP 236 9 3.8 ADC, UP 939 8 0.9 SCC, UP 267 5 1.9 Ca of UP/UP (NOS) 697 6 0.9 Lung Small Cell 320 3 0.9 Bladder Ca, NOS 39 2 5.1 Urothelial Ca 663 2 0.3 Pancreas Ca, NE 89 1 1.1 Pancreas Ca, NOS 244 1 0.4 Lung SCC 830 1 0.1 Ca-carcinoma; ADC-adenoCa; NE-neuroendocrine; UP-unknown primary; SCC-squamous cell cancer; NOS-not otherwise specified.
Ураження печінки у хворих на неспецифічний виразковий коліт
Authors: A.E. Dorofeyev, A.A. Dorofeyeva
Journal: GASTROENTEROLOGY (2017)

Актуальність. Стаття присвячена темі хронічних запальних захворювань кишечника, зокрема, приділяється увага неспецифічному виразковому коліту (НВК). НВК перебігає з розвитком низки позакишкових уражень, серед яких особливе місце відводиться змінам печінки і жовчовивідних шляхів. У зв’язку з цим було проведено дослідження, метою якого була оцінка поширеності, характеру і клінічних особливостей уражень печінки у хворих на НВК. Матеріали та методи. Під наглядом перебувало 180 пацієнтів із НВК, підтвердженим ендоскопічно і морфологічно. Усім пацієнтам проводили мультимодальне ультразвукове дослідження печінки, досліджували біохімічні ознаки цитолізу і/або холестазу при негативних серологічних маркерах вірусного гепатиту В, С, D і аутоімунного гепатиту. Також проводили біохімічне дослідження ліпідного спектра крові, а пацієнтам із підозрою на аутоімунні ураження печінки — аналіз спектру відповідних антитіл. Результати. Зі 180 хворих на НВК ураження печінки виявлені у 58 (32,2 %). Паренхіматозні ураження печінки виявлені у 40 (22,2 %) хворих на НВК, а зміни з боку жовчовивідних шляхів — у 18 (10,0 %) пацієнтів із НВК. Неалкогольний стеатогепатит (НАСГ), аутоімунний гепатит (АГ) і первинний біліарний цироз (ПБЦ) печінки виявлені у 40 (69,0 %) пацієнтів з НВК, а ураження поза- і жовчних проток і жовчного міхура — у 18 (31,0 %). Серед паренхіматозних уражень печінки домінував НАСГ (53,5 %). АГ діагностовано у 8,6 % пацієнтів, ПБЦ — у 5,2 % хворих на НВК. Усі хворі на НВК з НАСГ крім базисної терапії приймали препарат есенціальних фосфоліпідіву добовій дозі 1800 мг (по 2 капсули 3 рази на день) протягом трьох місяців. Після закінчення лікування тільки у 2 (6,5 %) пацієнтів зберігалися незначні скарги. До лікування у всіх обстежених хворих було виявлене достовірне підвищення АСТ і АЛТ в 2,3 і 2,2 раза відповідно, у поєднанні з підвищенням ГГТ в 3,7 раза порівняно з нормою, що може свідчити про помірно виражений синдром цитолізу. Після лікування у хворих відзначена тенденція до нормалізації ферментативного статусу, хоча показники залишалися підвищеними порівняно з нормою. Висновки. Ураження печінки виявлені у 32,2 % хворих, переважно при поширених формах, середньотяжкому і тяжкому перебігу і високій активності НВК. Для лікування НАСГ у хворих на НВК доцільне використання есенціальних фосфоліпідів.
Selegiline may be toxic in presence of increased dopamine concentrations
Authors: P H Yu, C T Lai, A A Boulton
Journal: BMJ (1996)

EDITOR,—In the trial carried out by the Parkinson's Disease Research Group of the United Kingdom levodopa plus selegiline seemed to offer no clinical benefit over levodopa alone, although less levodopa was required for the combined treatment.1 Mortality was significantly higher with the combined treatment. These findings contradict several earlier reports that selegiline, either alone or in combination, confers a beneficial effect in Parkinson's disease.

During the course of Parkinson's disease a progressive degeneration of nigrostriatal dopaminergic neurones occurs, with the remaining neurones becoming further stressed …
Comparison of long-term cardiac effects of 9- and 52-week trastuzumab in HER2-positive early breast cancer.
Authors: Mehmet Ali Nahit Sendur, Sercan Aksoy, Nuriye Özdemir, Hikmet Yorgun, Fatma Meric Yilmaz, Ozan Yazici, Cevdet Zungun, Kudret Aytemir, Kadri Altundag, Nurullah Zengin
Journal: Journal of Clinical Oncology (2014)

e11582 Background: Long term cardiac effects of Trastuzumab (T) is still not known. In this prospective study, we aimed to compare the long term cardiac effects of 9 and 52-week (w) T in adjuvant setting of HER2-(+) breast cancer (BC). Methods: Patients who completed 9w or 52w T at least 6 months before for the adjuvant setting in HER2-(+) BC were included to the study. 108 and 56 patients were treated with 9w and 52w T, respectively. The demographic characteristics of all patients enrolled in the study were recorded and echocardiographic measurements were made. Cardiac biomarkers were measured from serum samples in all patients. Results: Median follow-up was 32 (10-95) months. Baseline left ventricular ejection fraction (LVEF) was 65,5±3,4% ve 67,1±4,5% in 9w and 52w T groups, respectively (P=0.13). Symptomatic heart failure was not observed during T treatment in both groups. Asymptomatic LVEF decline was observed in 2 (1,9%) and 17 (30,3%) patients in 9w and 52w T groups, respectively and the incidence of LVEF decline significantly higher in 52w group (P<0.001). After median 24 months of the last T dose, mean LVEF was 64,3±2,7% in 9w group whereas 63,8±3,2% in 52w T group (P=0.29). In the subgroup analyses, mean LVEF was significantly lower in patients who developed cardiotoxicity during T mpared to who did not develop cardiotoxicity (61,9±3,6%, vs 64,4±2,6%, P=0.04). Cardiac biomarkers such as hs-CRP, TOS, CK-MB, troponin I, troponin T, pro-BNP and H-FABP was similar in both treatment groups. In the subgroup analyses serum Hs-CRP, TOS ve Pro-BNP levels were significantly higher in in patients who developed cardiotoxicity during trastuzumab treatment compared to who did not develop cardiotoxicity. Conclusions: At the end of 32 months, mean LVEF values and cardiac biomarkers were similar between two groups. But, in the subgroup analyses serum Hs-CRP, TOS ve Pro-BNP levels were significantly higher and mean LVEF values were significantly lower in patients who developed cardiotoxicity during T compared to who did not develop cardiotoxicity. Despite improvement of mean LVEF levels in the long term follow-up, cardiac biomarkers which show cardiac damage were still significantly higher in patients who developed cardiotoxicity.
Genomic Instability and Activation Of The DNA Damage Response Pathway Is An Independent Predictor Of Poor Prognosis, Is Associated With MYC Expression and Is a Promising Target For Therapy In Diffuse Large B Cell Lymphoma
Authors: Enrico Derenzini, Claudio Agostinelli, Ilaria Iacobucci, Enrica Imbrogno, Beatrice Casadei, Giovanni Martinelli, Stefano A Pileri, Pier Luigi Zinzani
Journal: Blood (2013)
Radiomic analysis of pseudo-progression compared to true progression in glioblastoma patients: A large-scale multi-institutional study.
Authors: Srishti Abrol, Aikaterini Kotrotsou, Ahmed Hassan, Nabil Elshafeey, Islam Hassan, Tagwa Idris, Kamel El Salek, Ahmed Elakkad, Kristin Alfaro, Shiao-Pei S. Weathers, Fanny E Moron, Jason Huse, Jeffrey S Weinberg, Amy B. Heimberger, Raymond Sawaya, Ashok J Kumar, John Frederick De Groot, Meng Law, Pascal Zinn, Rivka R. Colen
Journal: Journal of Clinical Oncology (2017)

2015 Background: Treatment-related imaging changes are often difficult to distinguish from true tumor progression. Treatment-related changes or pseudoprogression (PsP) subsequently subside or stabilize without any further treatment, whereas progressive tumor requires a more aggressive approach in patient management. Pseudoprogression can mimic true progression radiographically and may potentially alter the physician’s judgment about the residual disease. Hence, it can predispose a patient to overtreatment or be categorized as a non-responder and exclude him from the clinical trials. This study aims at assessing the potential of radiomics to discriminate PsP from progressive disease (PD) in glioblastoma (GBM) patients. Methods: We retrospectively evaluated 304 GBM patients with new or increased enhancement on conventional MRI after treatment, of which it was uncertain for PsP versus PD. 149 patients had the histopathological evidence of PD and 27 of PsP. Remaining 128 patients were categorized into PD and PsP based on RANO criteria performed by a board-certified radiologist. Volumetrics using 3D slicer 4.3.1 and radiomics texture analysis were performed of the enhancing lesion(s) in question. Results: Using the MRMR feature selection method, we identified 100 significant features that were used to build a SVM model. Five texture features (E, CS, SA, MP, CP) were found to be most predictive of pseudoprogression. On Leave One Out Cross-Validation (LOOCV), sensitivity, specificity and accuracy were 97%, 72%, and 90%, respectively. Conclusions: 3D radiomic texture features of conventional MRI successfully discriminated pseudoprogression from true progression in a large cohort of GBM patients.
Evaluation of nutritional risk among hospitalised patients using the malnutrition universal screening tool (MUST)
Authors: KS Nanda, SM Byrne, V Sukumaran, SE Patchett, FE Murray
Journal: Endoscopy (2005)

Introduction: Malnutrition is common amongst hospitalised patients and is frequently unrecognised and untreated. There are lack of guidelines and gold standards for screening for undernutrition. Malnutrition Universal Screening Tool (MUST) is a potential screening tool for this purpose.
Prescription opioid use in advanced COPD: benefits, perils and controversies
Authors: Natasha Smallwood, John Politis, Brian Le
Journal: European Respiratory Journal (2017)

We thank N.T. Vozoris for his comments and interest in the case report that we presented in the European Respiratory Journal of a patient with chronic obstructive pulmonary disease (COPD) who experienced respiratory depression after inadvertent opioid overdose while using opioids to manage refractory breathlessness [1]. The use of opioids to treat refractory breathlessness requires careful evaluation of risks and benefits <http://ow.ly/ylHT30bPzfu>
Serum Ceruloplasmin and Striatal Dopamine Transporter Density in Parkinson Disease
Authors: Yoo Sung Song, Jong-Min Kim, Kyeong Joon Kim, Ji Young Yun, Sang Eun Kim
Journal: Clinical Nuclear Medicine (2017)

In patients with Parkinson disease (PD), decreased serum ceruloplasmin levels have been observed. This study investigated a correlation between serum ceruloplasmin-along with its related serum markers- and striatal presynaptic dopaminergic denervation measured with I-FP-CIT SPECT.We analyzed a total of 141 de novo patients divided into 2 groups: the PD group (107 patients with PD) and the disease control group (34 patients with vascular pseudoparkinsonism, essential tremor, or drug-induced parkinsonism). Serum ceruloplasmin and related serum markers, such as copper, iron, total iron-binding capacity, and ferritin, were measured. Specific binding ratios of the striatum, caudate nucleus, putamen, and posterior putamen were obtained by I-FP-CIT SPECT.There was no difference in the serum markers, except for ceruloplasmin, between the 2 groups. Ceruloplasmin level was significantly lower in PD patients with longer symptom duration (>2 years) than in the disease control group (21.4 ± 3.4 vs 24.0 ± 3.8, P = 0.03). Serum ceruloplasmin had a significant correlation with specific binding ratios of the striatum, caudate nucleus, and putamen in a subgroup with longer symptom duration (P = 0.01, P = 0.02, P = 0.02, respectively, for the subgroup with symptom duration >1 year, and P < 0.01, P < 0.01, P = 0.04, respectively, for the subgroup with symptom duration >2 years).Decrease in serum ceruloplasmin had a positive correlation with a decrease in dopamine transporter density in PD patients with symptom duration of more than 1 year.
Breast cancer molecular subtypes association with clinical outcomes and race.
Authors: Ramses F. Sadek, Li fang Zhang, Houssein Talal Abdul Sater
Journal: Journal of Clinical Oncology (2017)

e12575 Background: Breast Cancer (BC) has been classified into four subtypes: Luminal A (LABC), Luminal B (LBBC), Triple negative (TNBC) and HER2-enriched (HER2e). BC mortality in Black women is significantly higher than in Whites and Asians. BC in Blacks has been characterized by higher grade and later stage. Causes of the Black-White BC survival disparity have been investigated, including differences in: diagnostic stage, socioeconomics, and comorbidities. These have led researchers to investigate the differences in tumor molecular subtype and their association with clinical outcomes and races. Methods: This study used the Surveillance, Epidemiology, and End Results – 18 (SEER-18) Registries research data between 2010 and 2013 that included over 212,000 patients. Descriptive statistics, Odds ratios (OR) and 95%Confidence intervals (CI) were used to study the association between BC stage, grade, and mortality and BC molecular subtypes across different races. We employed Cox regression models to explore the race disparity in BC mortality before and after controlling for BC molecular subtype and other clinical and social factors. Results: TNBC had more high grade cancer compared to HER2e subtype (OR, 1.5; CI, 1.3 - 1.8), LBBC (OR, 4.5; CI, 4.0 - 5.0) and LABC (OR, 12.2; CI, 11.2 – 13.3) for Black. BC mortality was higher in TNBC subtype compared to HER2e subtype (OR, 1.3; CI, 1.1 - 1.6), LBBC (OR, 2.4; CI, 2.0 - 2.9), and LABC (OR, 2.8; CI, 2.4 – 3.2) for Blacks. Results are consistent for all races. HER2e subtype had more late cancer stage compare to LBBC (OR, 1.2; CI, 1.0 - 1.4), TNBC (OR, 1.4; CI, 1.2 - 1.6) and LABC (OR, 2.1; CI, 1.8 - 2.4) in Blacks with similar results in all races. BC mortality in Blacks was higher compare with Whites (HR, 1.9; CI, 1.8 - 2.0) and Asian (HR, 2.7; CI, 2.5 - 3.0). After controlling for cancer subtype and other factors in the Cox regression model, the corresponding HRs ware significantly decreased to 1.2 (CI, 1.1 -1.3) and 1.6 (9CI, 1.5 -1.8). Blacks have heighst percent in stage IV and grade higer grade of disease. Conclusions: Molecular subtypes of BC contribute differently to risks of late cancer stage, high cancer grade and BC specific mortality. These differences are consistent in all races. The molecular subtypes and other social and clinical factors may explain part of the BC mortality race disparity.
Treatment patterns and associated adverse events among patients with metastatic triple-negative breast cancer.
Authors: Virginia G. Kaklamani, Neil M. Schultz, Debra E. Irwin, Nicole Fulcher, Virginia Noxon, Jun Wu, Bhavik J. Pandya, Ruth Kim, Arie Barlev, Scott Flanders
Journal: Journal of Clinical Oncology (2017)

e12576 Background: Triple-negative breast cancer (TNBC) accounts for 10–20% of all breast cancers and about 4% are metastatic (mTNBC) at diagnosis. This research aims to describe treatment patterns and associated adverse events (AEs) among mTNBC patients. Methods: MarketScan Commercial Claims and Encounters and Medicare Supplemental Database, linked to an oncology EMR database, was used to identify patients with mTNBC. Demographic factors, clinical characteristics, mTNBC treatment patterns (treatment type and initial regimen), and the incidence of associated AEs (rates per 100 person-years) were tabulated. Patients seen in oncology practices between January 1, 2011 and June 30, 2015 were included in the study and were required to have continuous enrollment overlap in the administrative claims data for 6 months before the first diagnosis and throughout the variable-length follow-up period. Follow-up ended due to death, end of continuous enrollment, or end of study (whichever occurred earlier). Results: The study identified 163 mTNBC patients with a mean age of 55 years. The average length of follow-up was 569 days and 34% died during the study period. Diabetes mellitus (22%) and anemia (16%) were the most common comorbid conditions at baseline. During the follow-up period, the majority of mTNBC patients received treatment (76%); the most common first-line treatments included cyclophosphamide (60%), paclitaxel (56%), doxorubicin (52%), carboplatin (25%), and docetaxel (23%), averaging 96 days in duration. In 47% of patients, treatment ended due to a switch. Over 96% of the patients experienced at least one AE during treatment, the most common being hematological (neutropenia, leukopenia, and anemia), gastrointestinal (nausea and vomiting), and other (pyrexia, fatigue, and dyspnea) [see table]. Conclusions: Several different chemotherapy agents were used to treat mTNBC. Adverse events were common among mTNBC patients initially treated with chemotherapy; the highest incident AEs were hematological. [Table: see text]
Laparoscopic assisted colorectal resection – The St Vincent's experience
Authors: D Mehigan, D Winter, K Sheahan, H Mulcahy, D O'Donoghue, J Hyland
Journal: Endoscopy (2005)

Aims: Despite having been first described over a decade ago, the laparoscopic approach to colorectal disease has only recently gained widespread popularity. We aimed to examine the clinical and oncological outcomes of laparoscopic assisted colorectal surgery in a single colorectal unit since it's introduction in September 2002.
Heterogeneity of variance in objective measures of aesthetic outcome associated with whole breast external beam radiotherapy compared with intraoperative radiotherapy in early breast cancer.
Authors: Norman R. Williams
Journal: Journal of Clinical Oncology (2016)

e12532 Background: Breast cancer is an increasingly treatable disease which means that many women will live a long time with the aesthetic consequences of their treatment. The majority of women with early breast cancer are given whole breast external beam radiotherapy (EBRT) after lumpectomy (breast conservation). It has been demonstrated, using an objective assessment of aesthetic outcome in patients from a randomised trial, that “redness”, a surrogate for radiation induced erythema grade I or II, is significantly greater after one year in patients receiving EBRT compared with those receiving intraoperative radiotherapy (IORT) using TARGIT. However, it has been observed that not all women given EBRT have detectable erythema, which implies that there is a greater variability in this group. In order to test this hypothesis a test of unequal group variances was performed. Methods: 991 frontal digital photographs were analysed from women participating in the TARGIT A Trial (NCT00983684) at four sites (Lublin, Mannheim, Copenhagen and Perth). Photographs taken at baseline (before surgery), 1 and 2 years (after surgery and EBRT or IORT) were objectively assessed, blinded to treatment received, by BCCT.core software which produces overall Harris scores, and scores for various measures of symmetry, colour and scar.The scores for colour were analysed in SAS v9.4 using PROC GLM. Results: cEMDL, a colour score associated with
Prevalence of hibernating myocardium and reversible silent myocardial ischemia in patients with heart failure due to coronary artery disease
Authors: JG Cleland, DJ Penneli, J Webster, SG Ray, A Bhattacharya, AJ Coats, A Lahiri, PW Macfarlane, JD Mule, Z Vered, Gordon Murray, Christmas Investigators
Journal: Journal of the American College of Cardiology (2002)
ADXS11-001 immunotherapy targeting HPV-E7: Preliminary survival data from a phase II study in Indian women with recurrent/refractory cervical cancer.
Authors: Partha Basu, Robert G. Petit
Journal: Journal of Clinical Oncology (2012)

5106 Background: ADXS11-001 immunotherapy is a live attenuated Listeria monocytogenes (Lm) bioengineered to secrete a HPV-16-E7 fusion protein targeting HPV transformed cells. The Lm vector serves as its own adjuvant and infects APC where it naturally cross presents, stimulating both MHC class 1 and 2 pathways resulting in specific T-cell immunity to tumors. Here we describe the preliminary survival data associated with ADXS11-001 administration in Lm-LLO-E7-015, a randomized phase II study being conducted in India in 110 patients with recurrent/refractory cervical cancer who have been treated previously with chemotherapy, radiotherapy or both. Methods: Patients are randomized to either 3 doses of ADXS11-001 at 1 x 10 9 CFU or 4 doses of ADXS11-001 at 1 x 10 9 CFU with cisplatin chemotherapy. Naprosyn and oral promethazine are given as premedications and a course of ampicillin is given 72h after infusion thereby clearing any residual vector. Patients receive CT scans at baseline and Days 84, 184, 273, 365 and 545. The primary endpoint is 12 month survival. Results: As of January 26, 2012, 88 patients have received 200 doses of ADXS11-001; with the percentage of patients alive at 6 months at 62% (34/55); at 9 months at 41% (15/37) and at 12 months at 40% (6/15). Tumor responses have been observed in both treatment arms with 3 complete responses (elimination of tumor burden) and 4 partial responses (≥30% reduction in tumor burden) by RECIST. One serious (Gr3) adverse event and 77 mild-moderate (Gr 1-2) adverse events possibly related to study treatment have been reported in 35% (31/88) of patients. The non-serious adverse events consisted predominately of transient, non-cumulative flu-like symptoms associated with infusion that responded to symptomatic treatment, or resolved on their own within hours of treatment. Conclusions: This immunotherapy can be safely administered to patients with advanced cancer alone and in combination with chemotherapy. ADXS11-001 is well tolerated and presents a predictable and manageable safety profile. Early signs of clinical benefit merit further investigation. Updated findings will be presented at the meeting.
An evaluation of appropriateness of plain abdominal radiographs in the A&amp;E department
Authors: R Naidoo, TR Gilbert, JP Ti, CM Smyth, A Gleeson, FE Murray
Journal: Endoscopy (2005)

Aim: To determine the appropriateness of plain abdominal radiographs(PFA), carried out prospectively, on patients assessed in the Accident and Emergency department(A/E).