tbuckley/cabot-search huggingface dataset:
Phase II trial of bendamustine plus rituximab for previously untreated patients with indolent B-cell non-Hodgkin lymphoma or elderly mantle cell lymphoma in Japan.
Authors: Kenichi Ishizawa, Michinori Ogura, Dai Maruyama, Yasunobu Abe, Kiyoshi Ando, Koji Izutsu, Yasuhito Terui, Imaizumi Yoshitaka, Noriko Fukuhara, Toshiki Uchida, Ilseung Choi, Ken Ohmachi, Go Yamamoto, Kensei Tobinai
Journal: Journal of Clinical Oncology (2016)

e19050 Background: No clinical evidence is available about the bendamustine and rituximab (BR) regimen as the first-line treatment of indolent B-cell non-Hodgkin lymphoma (B-NHL) or mantle cell lymphoma (MCL) in Asian populations. Methods: Previously untreated Japanese patients (pts) with high-tumor-burden indolent B-NHL and those with MCL aged 66 years and older received bendamustine 90 mg/m2/day on days 1 and 2, and rituximab 375 mg/m2on day 1 (day 0 of cycle 1) of each 28-day cycle (up to six cycles). The prophylactic use of acyclovir and sulfamethoxazole/trimethoprim was recommended when CD4 lymphocyte count lowered to < 200/μl. The primary endpoint was the complete response (CR) rate that was assessed by the independent review committee according to the International Workshop Criteria for NHL (JCO 1999). Results: Sixty-nine pts were treated (follicular 51, MALT 4, small lymphocytic 2, lymphoplasmacytic 2, and MCL 10). The median age of pts was 62 (39-79) years in indolent B-NHL and was 70 (67-77) in MCL, 71% were at FLIPI “intermediate” or “high” risk in indolent B-NHL, and all MCL pts had stage IV disease. The CR rates were 68% (95% CI: 54-79) and 70% (95% CI: 35-93) for indolent B-NHL and MCL, respectively. The ORR was 97% (95% CI: 88-100) for indolent B-NHL and was 90% (95% CI: 56-100) for MCL. The median duration of follow-up was 30.1 months. Estimated progression-free survival at 30 months was 72% (95% CI: 59-82%) in indolent B-NHL and was 68% (95% CI: 29-88%) in MCL. Major grade (G) 3/4 hematologic toxicities were lymphopenia (97%), CD4 lymphocytopenia (91%), and neutropenia (86%). Major nonhematologic toxicities were nausea (67%), constipation (65%), and malaise (54%). Infections occurred in 42 pts (61%). No G4 infection was found, while G3 infections occurred in five pts (febrile neutropenia 3, cytomegalovirus pneumonia 1, and bacterial infection 1). No treatment-related death was observed. Conclusions: The BR regimen as first-line treatment was highly effective and well tolerated in Japanese pts with high-tumor-burden indolent B-NHL and elderly pts with MCL, who received adequate prophylaxis for opportunistic infections. Clinical trial information: NCT01718691.
Inhibition of DNA damage repair by the CDK4/6 inhibitor palbociclib delays irradiated intracranial atypical teratoid rhabdoid tumor and glioblastoma xenograft regrowth
Authors: Rintaro Hashizume, Ali Zhang, Sabine Mueller, Michael D Prados, Rishi R Lulla, Stewart Goldman, Amanda M Saratsis, Andrew P Mazar, Alexander H Stegh, Shi-Yuan Cheng, Craig Horbinski, Daphne A Haas-Kogan, Jann N Sarkaria, Todd Waldman, C David James
Journal: Neuro-Oncology (2016)

Radiation therapy is the most commonly used postsurgical treatment for primary malignant brain tumors. Consequently, investigating the efficacy of chemotherapeutics combined with radiation for treating malignant brain tumors is of high clinical relevance. In this study, we examined the cyclin-dependent kinase 4/6 inhibitor palbociclib, when used in combination with radiation for treating human atypical teratoid rhabdoid tumor (ATRT) as well as glioblastoma (GBM).Evaluation of treatment antitumor activity in vitro was based upon results from cell proliferation assays, clonogenicity assays, flow cytometry, and immunocytochemistry for DNA double-strand break repair. Interpretation of treatment antitumor activity in vivo was based upon bioluminescence imaging, animal subject survival analysis, and staining of tumor sections for markers of proliferation and apoptosis.For each of the retinoblastoma protein (RB)-proficient tumor models examined (2 ATRTs and 2 GBMs), one or more of the combination therapy regimens significantly (P < .05) outperformed both monotherapies with respect to animal subject survival benefit. Among the combination therapy regimens, concurrent palbociclib and radiation treatment and palbociclib treatment following radiation consistently outperformed the sequence in which radiation followed palbociclib treatment. In vitro investigation revealed that the concurrent use of palbociclib with radiation, as well as palbociclib following radiation, inhibited DNA double-strand break repair and promoted increased tumor cell apoptosis.Our results support further investigation and possible clinical translation of palbociclib as an adjuvant to radiation therapy for patients with malignant brain tumors that retain RB expression.
Depressive symptoms, medical illness, and functional status in depressed psychiatric inpatients
Authors: J M Lyness, E D Caine, Y Conwell, D A King, C Cox
Journal: American Journal of Psychiatry (1993)

There is evidence that both psychiatric (especially affective) and medical illnesses contribute to physical disability. However, the differential contributions of specific psychiatric disorders and of medical pathology to functional status in psychiatric populations have not been studied. The authors therefore examined the contributions of depressive symptoms and medical illness to functional disability in depressed inpatients.This prospective investigation included 109 psychiatric inpatients with DSM-III-R major depression. Regression techniques were used to examine the contribution of demographic variables (age, sex, education), depressive symptom severity (Hamilton Rating Scale for Depression score), psychiatric function (Global Assessment of Functioning Scale score), organ system pathology (Cumulative Illness Rating Scale score), and medical disability (Karnofsky Performance Status Scale score) to overall functional status (Instrumental Activities of Daily Living and Physical Self-Maintenance scores). These relationships were also examined in older and younger subgroups.Greater age, female sex, and illness factors all contributed to poorer functional status. Of the illness factors, psychiatric pathology contributed more to low functional status than did medical illness. The predictive power came specifically from the functionally based measures of psychiatric and medical illness; a quantitative measure of symptoms (Hamilton depression scale) or organ pathology (Cumulative Illness Rating Scale) did not significantly predict overall functional status.Clinicians and researchers should recognize that symptomatic and functional assessments tap related but different domains and that both psychiatric and medical illnesses contribute to overall disability.
Neoadjuvant chemoradiation therapy for cholangiocarcinoma to improve R0 resection rate: The first report of phase II study.
Authors: Yu Katayose, Kei Nakagawa, Hiroshi Yoshida, Takanori Morikawa, Hiroki Hayashi, Takaho Okada, Masamichi Mizuma, Naoaki Sakata, Hideo Ohtsuka, Koji Fukase, Shinichi Yabuuchi, Masaharu Ishida, Takeshi AOki, Ryo Okada, Kunihiro Masuda, Kei Kawaguchi, Fuyuhiko Motoi, Takeshi Naitoh, Michiaki Unno
Journal: Journal of Clinical Oncology (2015)

402 Background: With the much-improved surgical techniques of hepatic lobectomy, but the long-term survival of patients undergoing such surgery remains far from satisfactory. Then, to improve the prognosis of cholangiocarcinoma patients, we have applied neoadjuvant chemoradiation therapy followed by conventional resection for possibly resectable cholangiocarcinoma, named NACRAC. Here, we analyzed and evaluated the Phase II (P-2) study. Methods: Patients with histologically or cytologically confirmed adenocarcinoma of the extra- and hilar cholangiocarcinoma were enrolled from 2008 to 2013 at Department Surgery, Tohoku University Hospital. The dose of gemcitabine was determined 600mg/m2 of gemcitabine with external beam radiation therapy (1.8-Gy daily fractions to a total dose of 45 Gy) ( Hepatogastroenterology. 2011;58(112):1866-72.). The primary endpoint of P-2 is R0-resection rate. We hypothesized that R0-resection rate become from 60% to 80%. Results: Total numbers of enrolled patients were 25 cases. 22 cases were operated, and 20 cases were resected. After chemoradiation, 3 cases were not operated by liver metastases, tumor progression, and heart failure. 2 cases were not resected by peritoneal carcinomatosis. One case was diagnosed as pancreatic cancer at the final pathological diagnosis. R0-resectinn cases were 17 cases. R0 resection rate was 89.6% (17/19) among operated cases. In recruited 24 cases (A pancreatic cancer was not included), R0 resection rate was 70.8% (17/24). Grade 3 and 4 adverse events (AE) were neutropenia, leukocytopenia, and Thrombocytopenia. No grade 5 AE and no fatal AE in this P-2 study. Conclusions: Neoadjuvant chemoradiation therapy with conventional resections appears to be effective and well tolerated. After both disease free survival and overall survival are going to be fixed, we will decide a proper indication of neoadjuvant therapy for cholangiocarcinoma. Trial Registration: UMIN Clinical Trials Registry (UMIN-CTR) UMIN UMIN000000992 and UMIN000001754 Clinical trial information: 000001754.
Phase 1 Study of a Hepcidin Antagonist, LY2787106, in Cancer-Associated Anemia
Authors: Saroj Vadhan-Raj, Rafat Abonour, Jonathan W. Goldman, David A. Smith, Christopher A. Slapak, Ramon V. Tiu, Xuejing Wang, Sophie Callies, Joanne Cox, Jay L. Tuttle, Yiu-Keung (James) Lau, Eric J. Roeland
Journal: Blood (2015)
Chronic hepatitis C in Austria, 1992–2006: genotype distribution and demographic factors
Authors: A Maieron, S Metz-Gercek, F Hackl, C Luger, A Ziachehabi, R Strauss, R Schöfl, H Mittermayer
Journal: Eurosurveillance (2010)

Chronic hepatitis C is a leading cause of end-stage liver disease and, with a worldwide prevalence of up to 3%, is a pandemic infectious disease. Austria, like most western European countries can be considered as a low prevalence country. This analysis aimed to assess the distribution of hepatitis C virus (HCV) genotypes in patients with chronic HCV infection in Upper Austria. Between September 1992 and December 2006, we identified 1,318 consecutive patients who tested positive for HCV RNA. Genotyping was routinely performed in 1,239 of the 1,318 patients, and in a subgroup of 617 patients data on the source of transmission were collected. Additionally we obtained data on liver histology and body mass index in a subsample of 273 of the 617 patients. Hepatitis C genotypes 1, 2, 3, 4, 6 and co-infections were found in 80.4%, 4.5%, 12.3%, 2.7%, 0.1% and 0.2% of the patients, respectively. There was a highly significant age difference in relation to gender at the time of diagnosis of chronic hepatitis C, with women being older than men (men: 45.0 years; women: 49.3 years; p&lt;0.0001). The number of new cases of chronic hepatitis C decreased substantially over the last decade, but although risk factors for obtaining HCV are well established, we did not find a decrease in the age of first diagnosis. Besides consistent screening in defined risk groups it is important to raise awareness for risk factors for HCV acquisition and liver disease progression.
Juvenile Psammomatoid Ossifying Fibroma
Authors: Rodrigo Cárdenas-Perilla, Consuelo Santamaria, Juan Manuel Muñoz-Acosta
Journal: Clinical Nuclear Medicine (2016)

Juvenile psammomatoid ossifying fibroma is a rare bone-forming tumor seen in craniofacial bones, which affects mainly young patients. We report scintigraphic and SPECT/CT findings of 2 patients diagnosed with this disease. One patient presented with suspicion of fibrous dysplasia and the other with suspected malignancy in the setting of a rapidly growing mass. Both cases highlight the importance of recognizing this type of tumor in young patients with abnormal uptake in paranasal bones and sinuses within the range of potential differential diagnoses including sarcomas, fibrous dysplasia, and odontogenic tumors.
Case 6-1985
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Leo C. Ginns, Eugene J. Mark
Journal: New England Journal of Medicine (1985)

Presentation of CaseA 62-year-old woman was admitted to the hospital because of a question of pneumonia.She was well until 19 months earlier, when she noticed a lump in the left breast. A mammographie study was reported to be negative. Five months before admission another mammographie examination disclosed an abnormal density in the left breast, and a biopsy of the lesion was performed elsewhere. Microscopical examination of the excised specimen revealed infiltrating ductal carcinoma. The patient was referred to this hospital.There was a history of smoking more than two packs of cigarettes daily for many years, with recent . . .
Abstract 13236: Prognostic Value of Heart Rate Depends on the Degree of Beta-Adrenergic Blockade in Chronic Heart Failure Patients with Reduced Ejection Fraction
Authors: Deddo Moertl, Alexandra Hammer, Raisa Hutuleac, Rudolf Berger
Journal: Circulation (2010)

Background:  The BEAUTIFUL-study has shown that a heart rate >70 bpm is associated with a worse prognosis in patients with ischemic heart disease and reduced ejection fraction. This finding supported the rationale of the SHIfT-trial which investigated the effects of selective heart rate reduction by ivabradine on top of optimized beta-blocker therapy in heart failure patients with reduced ejection fraction. Since the degree of beta-blockade might influence the prognostic importance of heart rate and thus the effectiveness of selective heart rate reduction on outcome, we evaluated the prognostic power of heart rate at different levels of beta-blockade.   Methods:  642 chronic heart failure patients (17% female, age 59±13y, LVEF  75% (n=163).   Results:  246 (38%) patients died after a follow-up period of 60months. We found a significant, positive interaction (p=0.026) between high heart rate and beta-blocker dosage showing that the power of heart rate >70 bpm to predict mortality increases as the beta-blocker dosage increases. Although in the total population high heart rate alone was not significantly associated with mortality risk, in the subgroup of patients with highest beta blockade high heart rate was a significant predictor of mortality (HR: 1.709 [1.061–2.754], p=0.0276), in contrast to patients with intermediate (HR: 1.151 [0.722–1.836], p=0.5536) and low beta-blocker dosages (HR: 0.992 [0.621–1.366], p=0.683).   Conclusions:  The prognostic importance of elevated heart rate in patients with chronic heart failure and reduced ejection fraction depends on beta-blocker dosage. The prognostic power of heart rate was only apparent in patients with highest doses of beta-blocker medication. These findings might be useful in interpreting the results of the SHIfT-Trial and in estimating the potential benefit of selective heart rate reduction in chronic heart failure.
Assessment and management of cirrhosis in people older than 16 years: summary of NICE guidance
Authors: P Harrison, B J Hogan, L Floros, E Davies
Journal: BMJ (2016)

#### What you need to know Clinical identification of cirrhosis remains imperfect, especially in people with compensated disease who are often asymptomatic. There is considerable variation in practice across England and Wales with regard to who is tested for cirrhosis and the diagnostic tests used.1 We provide guidance to aid diagnosis of cirrhosis, referral to specialist care for those at high risk of liver decompensation before they experience a defining event, and management of people with cirrhosis, including surveillance for and treatment of complications. Liver disease is the third most common cause of premature death in the UK. In England and Wales 60 000 people (1 in 1000) have cirrhosis, and mortality rates have increased by 400% since the 1970s.2 Liver biopsy was historically the standard test for the diagnosis of cirrhosis for all causes of liver disease. However, liver biopsy is associated with complications, such as pain and bleeding; it is an expensive test and is less acceptable to patients because of the morbidity associated with its use.3 New diagnostic technologies such as transient elastography and acoustic radiation force impulse imaging can diagnose cirrhosis with >90% sensitivity, and mean that it is now practical and acceptable to offer testing to a greater number of people. The Guideline Development Group (GDG) believe that
Evaluation of the measurement properties of symptom measurement instruments for atopic eczema: a systematic review
Authors: L. A. A. Gerbens, C. A. C. Prinsen, J. R. Chalmers, A. M. Drucker, L. B. von Kobyletzki, J. Limpens, H. Nankervis, Å. Svensson, C. B. Terwee, J. Zhang, C. J. Apfelbacher, P. I. Spuls
Journal: Allergy (2016)

Symptoms have been identified as a core outcome domain for atopic eczema (AE) trials. Various instruments exist to measure symptoms in AE, but they vary in quality and there is a lack of standardization between clinical trials. Our objective was to systematically evaluate the quality of the evidence on the measurement properties of AE symptom instruments, thereby informing consensus discussions within the Harmonising Outcome Measures for Eczema (HOME) initiative regarding the most appropriate instruments for the core outcome domain symptoms. Using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist and predefined criteria for good measurement properties on identified development and validation studies of AE symptom instruments, a best evidence synthesis was performed to draw an overall conclusion on quality of the instruments and to provide recommendations. Eighteen instruments were identified and evaluated. When the quality and results of the studies were considered, only five of these instruments had sufficient validation data to consider them for the core outcome set for the core outcome domain symptoms. These were the paediatric Itch Severity Scale (ISS), Patient-Oriented Eczema Measure (POEM), Patient-Oriented SCOring Atopic Dermatitis (PO-SCORAD), Self-Administered Eczema Area and Severity Index (SA-EASI) and adapted SA-EASI. ISS (paediatric version), POEM, PO-SCORAD, SA-EASI and adapted SA-EASI are currently the most appropriate instruments and therefore have the potential to be recommended as core symptom instrument in future clinical trials. These findings will be utilized for the development of a core outcome set for AE.
Single-cell Sequencing Reveals Variants in ARID1A, GPRC5A and MLL2 Driving Self-renewal of Human Bladder Cancer Stem Cells
Authors: Zhao Yang, Chong Li, Zusen Fan, Hongjie Liu, Xiaolong Zhang, Zhiming Cai, Liqin Xu, Jian Luo, Yi Huang, Luyun He, Chunxiao Liu, Song Wu
Journal: European Urology (2016)

Cancer stem cells are considered responsible for many important aspects of tumors such as their self-renewal, tumor-initiating, drug-resistance and metastasis. However, the genetic basis and origination of human bladder cancer stem cells (BCSCs) remains unknown. Here, we conducted single-cell sequencing on 59 cells including BCSCs, bladder cancer non-stem cells (BCNSCs), bladder epithelial stem cells (BESCs) and bladder epithelial non-stem cells (BENSCs) from three bladder cancer (BC) specimens. Specifically, BCSCs demonstrate clonal homogeneity and suggest their origin from BESCs or BCNSCs through phylogenetic analysis. Moreover, 21 key altered genes were identified in BCSCs including six genes not previously described in BC (ETS1, GPRC5A, MKL1, PAWR, PITX2 and RGS9BP). Co-mutations of ARID1A, GPRC5A and MLL2 introduced by CRISPR/Cas9 significantly enhance the capabilities of self-renewal and tumor-initiating of BCNSCs. To our knowledge, our study first provides an overview of the genetic basis of human BCSCs with single-cell sequencing and demonstrates the biclonal origin of human BCSCs via evolution analysis.Human bladder cancer stem cells show the high level of consistency and may derived from bladder epithelial stem cells or bladder cancer non-stem cells. Mutations of ARID1A, GPRC5A and MLL2 grant bladder cancer non-stem cells the capability of self-renewal.
GATA6 regulates EMT and tumour dissemination, and is a marker of response to adjuvant chemotherapy in pancreatic cancer
Authors: Paola Martinelli, Enrique Carrillo-de Santa Pau, Trevor Cox, Bruno Sainz Jr, Nelson Dusetti, William Greenhalf, Lorenzo Rinaldi, Eithne Costello, Paula Ghaneh, Núria Malats, Markus Büchler, Marina Pajic, Andrew Biankin, Juan L. Iovanna, John Neoptolemos, Francisco X. Real
Journal: Gut (2016)

<h3>Background and aims</h3> The role of GATA factors in cancer has gained increasing attention recently, but the function of GATA6 in pancreatic ductal adenocarcinoma (PDAC) is controversial. GATA6 is amplified in a subset of tumours and was proposed to be oncogenic, but high GATA6 levels are found in well-differentiated tumours and are associated with better patient outcome. By contrast, a tumour-suppressive function of GATA6 was demonstrated using genetic mouse models. We aimed at clarifying GATA6 function in PDAC. <h3>Design</h3> We combined GATA6 silencing and overexpression in PDAC cell lines with GATA6 ChIP-Seq and RNA-Seq data, in order to understand the mechanism of GATA6 functions. We then confirmed some of our observations in primary patient samples, some of which were included in the ESPAC-3 randomised clinical trial for adjuvant therapy. <h3>Results</h3> GATA6 inhibits the epithelial–mesenchymal transition (EMT) in vitro and cell dissemination in vivo. GATA6 has a unique proepithelial and antimesenchymal function, and its transcriptional regulation is direct and implies, indirectly, the regulation of other transcription factors involved in EMT. GATA6 is lost in tumours, in association with altered differentiation and the acquisition of a basal-like molecular phenotype, consistent with an epithelial-to-epithelial (ET<sup>2</sup>) transition. Patients with basal-like GATA6<sup>low</sup> tumours have a shorter survival and have a distinctly poor response to adjuvant 5-fluorouracil (5-FU)/leucovorin. However, modulation of GATA6 expression in cultured cells does not directly regulate response to 5-FU. <h3>Conclusions</h3> We provide mechanistic insight into GATA6 tumour-suppressive function, its role as a regulator of canonical epithelial differentiation, and propose that loss of GATA6 expression is both prognostic and predictive of response to adjuvant therapy.
Multiple access and hospitalization predictors in patients with Urological Cancer: a retrospective analysis
Authors: S.K. Garattini, C. Fontanella, K. Rihawi, C. Bozza, C. Andreetta, V. Merlo, P. Ermacora, C.S. Sacco, G. Aprile, F. Puglisi, G. Fasola
Journal: Annals of Oncology (2015)