tbuckley/cabot-search huggingface dataset:
Identifying arthralgia suspicious for progression to rheumatoid arthritis
Authors: Kulveer Mankia, Jackie Nam, Paul Emery
Journal: Annals of the Rheumatic Diseases (2016)

We read with interest the article by van Steenbergen et al 1 in which a definition for arthralgia suspicious for progression to rheumatoid arthritis (RA) was proposed. The authors used a three-phase Delphi exercise to crystallise the concept of clinically suspect arthralgia (CSA), which is inherently subjective, into a core set of definable parameters. We agree that this set of characteristics should provide a useful secondary care framework for identifying homogeneous at-risk populations for future clinical studies. Recent data suggest that rheumatologists can use symptoms and signs to identify which patients with arthralgia referred to them will imminently develop RA.2 ,3 In the current cohort, up to 20% of individuals identified as CSA by their rheumatologist developed RA during follow-up, the majority doing so …
Cost Utility Analysis of Topical Steroids Compared With Dietary Elimination for Treatment of Eosinophilic Esophagitis
Authors: Cary C. Cotton, Daniel Erim, Swathi Eluri, Sarah H. Palmer, Daniel J. Green, W. Asher Wolf, Thomas M. Runge, Stephanie Wheeler, Nicholas J. Shaheen, Evan S. Dellon
Journal: Clinical Gastroenterology and Hepatology (2016)
The Immunoglobulin Gene Repertoire of Low-Count CLL-Like MBL Is Different from CLL: Diagnostic Considerations and Implications for Clinical Monitoring
Authors: Antonis Dagklis, Claudia Fazi, Cinzia Sala, Valeria Cantarelli, Cristina Scielzo, Roberto Massacane, Daniela Toniolo, Federico Caligaris-Cappio, Kostas Stamatopoulos, Paolo Ghia
Journal: Blood (2008)
Development of a clinical diagnostic matrix for characterizing inherited epidermolysis bullosa
Authors: V.K. Yenamandra, C. Moss, V. Sreenivas, M. Khan, S. Sivasubbu, V.K. Sharma, G. Sethuraman
Journal: British Journal of Dermatology (2016)

Accurately diagnosing the subtype of epidermolysis bullosa (EB) is critical for management and genetic counselling. Modern laboratory techniques are largely inaccessible in developing countries, where the diagnosis remains clinical and often inaccurate. To develop a simple clinical diagnostic tool to aid in the diagnosis and subtyping of EB. We developed a matrix indicating presence or absence of a set of distinctive clinical features (as rows) for the nine most prevalent EB subtypes (as columns). To test an individual patient, presence or absence of these features was compared with the findings expected in each of the nine subtypes to see which corresponded best. If two or more diagnoses scored equally, the diagnosis with the greatest number of specific features was selected. The matrix was tested using findings from 74 genetically characterized patients with EB aged > 6 months by an investigator blinded to molecular diagnosis. For concordance, matrix diagnoses were compared with molecular diagnoses. Overall, concordance between the matrix and molecular diagnoses for the four major types of EB was 91·9%, with a kappa coefficient of 0·88 [95% confidence interval (CI) 0·81–0·95; P < 0·001]. The matrix achieved a 75·7% agreement in classifying EB into its nine subtypes, with a kappa coefficient of 0·73 (95% CI 0·69–0·77; P < 0·001). The matrix appears to be simple, valid and useful in predicting the type and subtype of EB. An electronic version will facilitate further testing.
Intravenous fosfomycin—back to the future. Systematic review and meta-analysis of the clinical literature
Authors: B. Grabein, W. Graninger, J. Rodríguez Baño, A. Dinh, D.B. Liesenfeld
Journal: Clinical Microbiology and Infection (2016)

We conducted a systematic review and meta-analysis to summarize the clinical evidence and usage patterns of intravenous fosfomycin from its development to the present time.PubMed, the Cochrane Library and local journals were searched for relevant studies reporting aggregated data of intravenous fosfomycin use in adults and children, with no restrictions regarding study design. Single case reports were excluded. Data were systematically abstracted for all included studies. Clinical and microbiological efficacy from randomized controlled and comparative observational studies were synthesized using meta-analysis to calculate pooled effect sizes.In all, 128 studies on intravenous fosfomycin in 5527 patients were evaluated. Fosfomycin was predominantly used for sepsis/bacteraemia, urinary tract, respiratory tract, bone and joint, and central nervous system infections. No difference in clinical (OR 1.44, 95% CI 0.96-2.15) or microbiological (OR 1.28, 95% CI 0.82-2.01) efficacy between fosfomycin and other antibiotics was observed in comparative trials. The pooled estimate for resistance development during fosfomycin monotherapy was 3.4% (95% CI 1.8%-5.1%). Fosfomycin showed a favourable safety profile, with generally mild adverse events not requiring discontinuation of treatment. Included studies explored intravenous fosfomycin as an anti-staphylococcal agent in monotherapy and combination therapy, whereas studies from 1990 focused on combination therapy (fosfoymcin + β-lactams or aminoglycosides) for challenging infections frequently caused by multidrug-resistant organisms.Intravenous fosfomycin can play a vital role in the antibiotic armamentarium, given its long history of effective and safe use. However, well-designed randomized controlled trials are still desired.
SL-401 Mediates Potent Cytotoxicity Against CD123+ AML and MDS with Excess Blasts and Demonstrates Therapeutic Benefit in PDX Model
Authors: Rajeswaran Mani, Swagata Goswami, Bhavani Gopalakrishnan, Rahul Ramaswamy, Ronni Wasmuth, Minh Tran, Xiaokui Mo, Amber Gordon, Donna Bucci, David Lucas, Christopher L. Brooks, Alison R. Walker, William Blum, John C. Byrd, Gerard Lozanski, Sumithra Vasu, Natarajan Muthusamy
Journal: Blood (2016)
Correlation between human epidermal growth factor receptor 2 (HER2) status and central nervous system (CNS) involvement in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Angela Gernone, Vincenzo Pagliarulo, Francesco Silvestris, Arcangelo Pagliarulo
Journal: Journal of Clinical Oncology (2012)

210 Background: The incidence of CNS metastasesin prostate cancer is very low. Recent data suggest that HER-2/neu is involved in progression of prostate cancer. Docetaxel-based chemotherapy has provided a survival advantage for mCRPC. The purpose of this retrospective study was to evaluate the relation between HER-2 status and risk of CNS metastases in pts with mCRPC treated with docetaxel. Methods: From 2003 to 2010, 130 pts with mCRPC were treated with 3wk docetaxel 75 mg/mq. 72/130 pts were retreated with the same regimen on disease progression. 50 out of these 72 pts received second docetaxel retreatment. All pts had bone metastases. Pts underwent total body CT scan before starting docetaxel chemotherapy and every 6 months during treatment. The median age was 66 (41–88), median baseline PSA: 110 ng/ml (range 5–1100), median ECOG Performance Status: 1 (range 0–2). The data on 130 pts, who underwent diagnostic biopsy or potentially curative resection , were reviewed. Tissue blocks from primary prostate cancer tissues were obtained. Grade 3 of the HER-2 by IHC staining was defined as a positive result or gene amplification by FISH. 10 out of these 50 pts receiving second docetaxel retreatment were diagnosed with CNS metastases. Results: CNS metastases were observed in HER-2 positive pts. 6/10 pts presented parenchymal metastases: 4 pts were asymptomatic, 3 pts underwent metastasectomy and all of them received palliative whole-brain RT. 4/10 pts presented leptomeningeal metastases with neurological symptoms and 2 of them received palliative whole-brain RT. The median time from prostate cancer diagnosis to the date of diagnosis of CNS metastases was 6 years (1–8). The median time from first cycle of docetaxel to the date of diagnosis of CNS metastases was 3 years (1.5–4). Conclusions: These preliminary data demonstrated that HER-2 expression confers an increased risk of CNS metastases in mCRPC and constitutes a therapeutic challenge. The apparent increase of CNS presentation may be related to the effectiveness of systemic therapy. These informations support the further evaluation of neurological symptoms in long-term docetaxel treated pts.
National Surgical Adjuvant Breast and Bowel Project Update
Authors: Victor G. Vogel, Joseph P. Costantino, D. Lawrence Wickerham, Walter M. Cronin
Journal: Clinical Cancer Research (2003)

Following up on the results of recent completed trials, several major breast cancer prevention trials are either underway or impending. In the Study of Tamoxifen and Raloxifene trial, eligible women are at least 35 years of age and postmenopausal, with either lobular carcinoma in situ or a 5-year risk of invasive breast cancer of at least 1.67%. The study will compare the ability of 5 years of tamoxifen or raloxifene to reduce the incidence of breast cancer. Subjects are randomly assigned to receive either 20 mg of tamoxifen or 60 mg of raloxifene daily. After 3 years of recruitment, 13,647 women have been randomized (20.7% of those eligible). The median age of randomized women is 58 years (mean age, 58 years), and their median 5-year risk of breast cancer is 3.3% (mean 5-year risk of breast cancer, 4.0%). Hysterectomy was reported by 52.5% of the randomized women; lobular carcinoma in situ was reported by 8.4% of subjects before randomization. In the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-24 trial, 1,804 women with ductal carcinoma in situ were randomly assigned tamoxifen after lumpectomy and radiation therapy. Women in the tamoxifen group had fewer breast cancer events at 5 years than did those on placebo (8.2% versus 13.4%, P = 0.0009). The proposed NSABP B-35 trial will have the same design as NSABP B-24 but will compare tamoxifen with anastrozole in postmenopausal women. Outcomes will include both ipsilateral and contralateral new breast cancer and recurrences, as well as the occurrence of regional and distant disease. Enrollment will begin in early 2003.
A novel web-based tool for risk quantification and objectification of treatment of renal cell carcinoma.
Authors: D. Canter, A. Kutikov, J. Bland, S. Sterious, B. Rozenfeld, D. Chen, R. Uzzo
Journal: Journal of Clinical Oncology (2011)

382 Background: Despite the development of treatment guidelines, the management of renal cell carcinoma (RCC) remains overly subjective. Nomograms and statistical algorithms promise more objective decision making by patients and physicians by quantifying risk. Unfortunately, these tools remain underutilized in daily clinical practice because they are both cumbersome and time-consuming. We sought to create a novel website where all the available and relevant nomograms for RCC could be easily accessible for patients and practitioners, minimizing the subjectivity associated with clinical risk stratification and decision-making. Methods: The existing literature was reviewed to identify published nomograms relevant to RCC. Nomograms were grouped by defining characteristics (preoperative versus postoperative predictive models, predictive models for metastatic disease, etc). Additional operationalized models included staging tools, surveillance models and cancer statistics. Nomograms were selected based on predictive accuracy, applicability, and ability to objectify risk stratification. Only nomograms with an AUC of greater than 0.7 were operationalized. The times required to extract clinical metrics for four hypothetical clinical scenarios were compared between the original paper version and our web-based model. Results: www.cancernomograms.com organizes and operationalizes interactive predictive models for RCC for both physicians and patients. Each model was developed as an independent software program and deployed as an interactive flash object embedded in an HTML page allowing point of care risk calculation. In an initial sample of 15 subjects, the website decreased nomogram metric output from minutes to seconds, proving that utilization of a computer-based platform for these nomograms is faster (p=0.0003). Conclusions: www.cancernomograms.com is a novel website that allows point of care risk quantification and objectified decision making using published statistical models. This web tool may help improve physician and patient communication and clinical care. No significant financial relationships to disclose.
Arginine (R) at Position 595 in FLT3 Is Critical for Transforming Potential of FLT3-Length Mutations.
Authors: Sridhar Vempati, Ruth Schwab, Theodora Malamoussi, Martin Dugas, Gudrun Mellert, Susanne Schnittger, Wolfgang Hiddemann, Karsten Spiekermann
Journal: Blood (2005)
Relative dose intensity (RDI) assessment in an academic center.
Authors: A. Arnaout, H. Leblebjian, S. Bartel, M. J. Hassett
Journal: Journal of Clinical Oncology (2011)

139 Background: Patients with early breast cancer treated in the adjuvant setting realize maximum benefit as to disease- free and overall survival when they receive their full planned dose of chemotherapy. Due to the aggressive treatment regimens, patients are at increased risk of dose delays and reductions, which result in reduced RDI. Studies have shown that at RDI &lt; 85%, treatment outcomes are compromised. We sought to calculate the RDI attained in our breast cancer clinic and identify factors contributing to decreased RDI. Methods: We retrospectively reviewed records of 383 patients treated between January 2008 and December 2009. Treatment blocks were reviewed separately to better identify contributing factors to decreased RDI. Regimens were dose-dense doxorubicin and cyclophosphamide (ddAC), dd-paclitaxel (ddT), paclitaxel and trastuzumab (TH), and TH post ddAC. G-CSF support was noted when present. Dose reductions and dose delays (in days) with reason(s) were recorded for patients with RDI &lt; 85%. Patients who switched care or regimen were excluded from this study. Results: Of the 383 patients, 150 received ddAC; 101 ddT; 67 TH and 65 TH post ddAC. Of these, the percentage of patients with RDI &lt; 85% was 10.4%. RDI was &lt;85% in 8.7%, 6.9%, 14.9%, and 15.4% in the ddAC, ddT, TH, and TH post ddAC regimens, respectively. The major impediments were neutropenia in the anthracycline containing regimen, neuropathy with taxanes, and cardiotoxicity with trastuzumab. No dose delays were seen for administrative issues. Conclusions: Our results show that 10.4% of treated patients had RDI &lt; 85%. These results were superior when compared to historic data for same regimens. Major reasons for decreased RDI were neutropenia, neuropathy, and cardiotoxicity. Improving risk assessment of neutropenia before initiating treatment could improve RDI in this patient population. Prophylaxis with vitamin B6 may help reduce incidence of neuropathy. Efforts to assure on-schedule treatments should be maintained. This includes comprehensive paramedical support to overcome any hurdles to on-time treatment. Proper education of patients on the importance of RDI can increase awareness of the value of cooperating with the provider and encourage them to persevere with the treatment.
At what timescale does consciousness operate?
Authors: Bernhard Hommel, Reinout W Wiers
Journal: Behavioral and Brain Sciences (2016)

While applauding Morsella et al. for linking consciousness to action control, we ask what their theory implies regarding the exact functionality of consciousness and the timescale at which it operates. Does consciousness operate on, and resolve the conflict it emerges from (despite its slowness), or does it operate on future conflicts that it might resolve by externalizing/socializing cognitive control?
Stage IV breast cancer in the community hospital setting: Primary tumor extirpation effect on overall survival.
Authors: J. A. Tjoe, L. A. Robinson, J. Stephenson, J. J. Marx
Journal: Journal of Clinical Oncology (2011)

90 Background: Publications from academic centers and national cancer databases suggest a survival advantage for women who undergo primary tumor extirpation in the setting of known distant disease. We asked if similar findings exist in a community hospital setting. Methods: 15,887 patients entered in a longitudinally maintained breast cancer database (encompassing a system network of 13 community hospitals) during 1985-2009 were analyzed for those diagnosed with stage IV disease upon initial presentation. The cohort was divided into those who underwent primary tumor resection, and those who did not. The two subgroups were compared for patient demographics, tumor characteristics, sites of distant metastases, systemic treatment, and overall survival (OS). Results: 643 (4.05%) presented with an intact primary breast malignancy and synchronous distant metastasis. Median age at diagnosis: 66 years (range 22-96). Median OS: 15 months (range 0-249). 264 (41.1%) patients underwent primary tumor resection as part of first course treatment. On Kaplan-Meier univariate analysis, patients who underwent surgical extirpation of the primary tumor demonstrated improved median OS compared to those who did not (26 vs 10 months; p&lt;0.0001, HR 0.52). Age at diagnosis &lt;50 (p=0.0003, HR 0.65) and oligometastasis to bone (p=0.0002, HR 0.72) were statistically significant predictors of improved OS. Race, primary tumor size, and ER status alone did not influence OS. Those ER+ patients who underwent primary tumor excision in addition to chemotherapy and/or hormonal therapy fared significantly better than those treated with systemic therapy alone (32 vs 17 months; p&lt;0.0001). Chemotherapy 16+ weeks prior to surgery improved OS compared to those who had surgery &lt;16 weeks after starting chemotherapy. While there was no difference with regards to type of resection (partial vs simple vs modified radical mastectomy), clear margins were imperative to optimize OS. Conclusions: Patients with stage IV breast cancer treated at community hospitals also demonstrate improved OS after primary tumor extirpation, especially in the context of a multimodality approach combining chemotherapy and/or hormonal therapy preceding surgery.
High-risk prostate cancer treated with I-125 brachytherapy.
Authors: Abigail Lauren Stockham, Chandana A. Reddy, Kevin L. Stephans, Jay P. Ciezki, Rahul D. Tendulkar
Journal: Journal of Clinical Oncology (2012)

134 Background: High-risk prostate cancer (HRPC) is commonly defined as Gleason score (GS) ≥ 8, PSA ≥ 20 ng/ml, and/or T3-T4 disease, or having a combination of two intermediate risk factors. Multimodality therapy is commonly utilized for HRPC due to concerns of extra-prostatic extension or seminal vesicle invasion. The purpose of this study was to examine the outcomes of HRPC patients treated with wide brachytherapy implant alone. Methods: From our IRB-approved registry, we performed a retrospective review of all patients with HRPC and no radiographic evidence of metastatic disease who were treated with I-125 prostate brachytherapy at Cleveland Clinic. Patients who received supplemental external beam radiation were excluded. Characteristics analyzed on univariate analysis included initial PSA, GS, clinical stage, use of androgen deprivation (AD), dose to 90% of the prostate (D90), and volume of the gland receiving 100% of the prescribed dose (V100) of 144 Gy. Endpoints included biochemical relapse free survival (bRFS) defined by nadir PSA + 2 ng/ml, and distant metastases. Results: From 7/1997- 6/2011, 389 patients with HRPC were treated with I-125 prostate brachytherapy. Median age was 70 years. Patients with GS 8-10 accounted for 40% of cases, 72% were clinical stage T1c, and the median initial PSA was 11.3 ng/ml. Concurrent AD was utilized in 67% of patients and the median D90 was 144.8 Gy (range 75.7 – 248.33 Gy). At a median follow-up of 27 months, the 5-year bRFS was 75.7% and the 5-year distant metastases-free survival was 93.1%. Nine patients died of prostate cancer (crude rate 2.3%). No clinical or treatment factors were identified that correlated with the development of biochemical failure, including the use of AD (p = 0.19, HR 0.612). Conclusions: Brachytherapy for patients with HRPC yields favorable outcomes at early follow up time. Longer follow-up and prospective studies are needed for further analysis.
Outcome of patients (pts) with renal medullary carcinoma (RMC) treated in the era of targeted therapies (TT): A multicenter experience.
Authors: N. M. Tannir, Z. Dubauskas Lim, B. N. Bekele, E. D. Johnson, P. Tamboli, U. N. Vaishampayan, E. R. Plimack, K. Rathmell, E. Jonasch
Journal: Journal of Clinical Oncology (2011)

386 Background: RMC is a rare, highly aggressive primary neoplasm of the kidney that almost exclusively afflicts young black pts with sickle cell hemoglobinopathies, primarily sickle cell trait. The primary objectives of this study were to evaluate the clinical characteristics and treatment outcome of RMC pts. Methods: We retrospectively reviewed the medical records of pts diagnosed with RMC at four US institutions between 2000 and 2010. Overall survival (OS) was determined from initial diagnosis to date of death or last follow up (F/U). The time interval from date of metastasis to death or last F/U (OSm) was also determined. Kaplan-Meier methods were used to estimate OS and OSm. Results: 20 RMC pts were identified. All pts were black; 14 (70%) were males; 18 had sickle cell trait, 1 had sickle thalassemia and 1 not tested. 19 presented with stages III or IV; 7 (35%) had nephrectomy. Nineteen pts had ≥ 2 metastatic sites. Twelve pts had performance status [PS] 0/1; eight pts had PS 2/3. For the OS analysis, data on 16 pts were available and for the OSm analysis, data on 20 pts were available. The median follow up time for the OS analysis was 722 days. Thirteen of 16 pts died with median OS of 421 days [95%CI: 225–546]. Sixteen of 20 pts died in the OSm analysis with median OSm of 378 days [95%CI: 225–487]. Frontline therapy consisted of TT [sunitinib (5), bevacizumab + erlotinib (1), imatinib (2)], chemotherapy (C) [platinum/gemcitabine or taxane (7), gemcitabine/doxorubicin (2)], C + TT [gemcitabine/cisplatinum/bevacizumab (2), imatinib/doxorubicin (1)]. Three pts achieved a partial response (PR) in first-line (2 with C, 1 with C + TT). Twelve pts received second-line systemic therapies; 4 achieved PR (1 with bevacizumab/erlotinib, 2 with C, 1 with C + TT). Among 15 pts who had TT at any time during their treatment course, only 1 pt had PR. Conclusions: The prognosis of RMC pts remains poor despite initial palliation with systemic therapy. Collaborative multi-institutional efforts are needed to better understand the biology of this disease and improve treatment strategies. No significant financial relationships to disclose.