tbuckley/cabot-search huggingface dataset:
Polymorphisms in angiogenesis related genes predict clinical outcome in patients (pts) with metastatic colorectal cancer (mCRC) treated with first line 5-FU or capecitabine in combination with oxaliplatin and bevacizumab (FOLFOX/BV or XELOX/BV)
Authors: O. S. Shaye, H. M. Chang, D. Y. Yang, J. Shriki, A. M. Schultheis, W. Zhang, G. Lurje, S. Iqbal, H. J. Lenz, A. B. El- Khoueiry
Journal: Journal of Clinical Oncology (2007)

10576 Background: The inhibition of angiogenesis is central to the mechanism of action of BV, a monoclonal antibody to vascular endothelial growth factor (VEGF). We evaluated functionally significant polymorphisms of genes involved in the angiogenesis/VEGF pathway as potential molecular predictors of clinical outcome in pts with mCRC who received BV as part of their frontline therapy. These genes included: VEGF, VEGF receptor 2 (KDR), neuropilin 1 (NRP 1), Interleukin (IL) 6 and 8, IL receptor 1 and 2 (CXCR 1, CXCR 2) adrenomedullin (AM), leptin, fibroblast growth factor receptor 4 (FGFR4), tissue factor (TF), matrix metalloproteinases (MMP 2,7,9), epidermal growth factor receptor (EGFR), aryl hydrocarbon receptor nuclear translocator (ARNT), and nuclear factor kappa b (NFkb). Methods: PCR-RFLP assays were performed on genomic DNA extracted from the blood of 30 pts with mCRC treated with first-line FOLFOX/BV or XELOX/BV at USC. Results: the cohort consisted of 21 males and 9 females with a median age of 56 years (range: 29–81). 20 pts received XELOX/BV as part of an on-going phase II study, 10 pts received FOLFOX/BV. Radiologic response was evaluable in 27/30 pts: 2/27 (7%) complete response (CR), 14/27 (52%) partial response (PR), and 10/27 (37%) stable disease (SD) and 1/28 (4%) progressive disease. At a median follow-up of 19.4 months, 16/30 pts progressed with a median progression free survival (PFS) of 11.8 months. Pts homozygous A/A at the leptin 5'UTR region had a higher probability of response than pts with the G/A or G/G genotypes (p=0.03, Fisher's exact test). Pts with one or more G allele (G/G or A/G) at locus -181 in the promoter region of MMP7 had a higher probability of response than pts with the AA genotype (p=0.014, Fisher's exact test). There were statistically significant associations between genomic polymorphisms of KDR, CXCR2, MMP7 and PFS (&lt;0.05, Log-rank test). Conclusions: This pilot study demonstrated, in a preliminary fashion, the potential predictive and prognostic value of several genomic polymorphisms in pts with mCRC treated with FOLFOX/BV or XELOX/BV. No significant financial relationships to disclose.
Treatment of Dupuytren Contracture With Injectable Collagenase Within the Veterans Affairs System
Authors: Stephen Duquette, Ryan Kuster, Tyler Evans, William Wooden, Imtiaz Munshi, Adam Cohen, Sunil S. Tholpady
Journal: JAMA Surgery (2016)

Treatment of Dupuytren Contracture With Injectable Collagenase Within the Veterans Affairs SystemDupuytren contracture is a debilitating disease involving abnormal thickening of the palmar fascia, resulting in pits, nodules, and cords that lead to contracture of the digits.Prevalence in the veteran population is approximately 306 per 100 000 indiv iduals. 1 Surgic al management of Dupuytren contracture includes removal or release of the fascia via open fasciectomy, open fasciotomy, closed fasciotomy, and most recently, injectable collagenase.A doubleblind placebo-controlled trial published in 2010 showed a significantly greater mean increase in range of motion in the group that received collagenase (35.4°) than in the group that received placebo (7.6°) (P < .001); in addition, 50.7% of all joints treated with collagenase achieved a range of motion 0°to 5°of normal. 2 With the US Food and Drug Administration approval of collagenase from Clostridium histolyticum in 2010, it was predicted that there would be increased use of collagenase, with an associated decrease in palmar fasciectomy and fasciotomy within the Veterans Affairs (VA) system.
We want the best doctors in Wales, wherever they come from, says first minister
Authors: Abi Rimmer
Journal: BMJ (2016)

Carwyn Jones, the first minister of Wales, tells Abi Rimmer that his country will always welcome doctors from overseas as he sets out plans to increase GP recruitment

Jeremy Hunt, England’s health secretary, announced plans this month for the NHS to employ fewer doctors from overseas and to be self sufficient in doctors by 2025.1 The UK prime minister, Theresa May, followed his announcement by saying that doctors from overseas could remain working in the NHS for an “interim period” until enough UK doctors had been trained.2

Carwyn Jones, the first minister of Wales, says that this attitude is completely at odds with the view held by the Welsh government. “One thing I do want to say very, very strongly is that we welcome people from outside of …
Case series: Paclitaxel (P) and pegfigrastim (PF)-induced hypersensitivity pneumonitis (HSP) in breast cancer patients (pts)
Authors: L. Cream, A. C. Barochia, J. Sivik, R. Kass
Journal: Journal of Clinical Oncology (2009)

e11631 Background: P, a chemotherapeutic agent, extensively used in management of solid tumors. Although hypersensitivity reactions from P are common; HSP is rarely reported. We report 3 pts with early stage, high risk breast cancer, who developed HSP while receiving dose dense (DD) P with PF support. Methods: C#1 51 yr old woman (W) was diagnosed (Di) with triple negative (TN), infiltrating duct carcinoma (ca) with nodal metastasis. Neoadjuvant chemo (NC) with DD adriamycin 60 mg/m2 (A) and Cyclophosphamide 600 mg/m2 (C) was started. She completed 4 cycles of AC with PF 6 mg SQ given day 2 of each cycle without complications. Several days after her first dose of P with PF, she experienced dyspnea on exertion (DOE) and a non productive cough (NPC). CT of chest (CC) revealed ground glass opacity more in upper lungs, suggestive of HSP, and echocardiogram (echo) was within normal limits (WNL). She rapidly improved with steroid (S). C#2 46 yr w was Di with hormone positive, her 2 negative, infiltrating duct ca with nodal involvement. NC with DD AC followed by P was started. She completed 4 cycles of AC with minimal toxicity followed by DDP. After the third P infusion, she developed NPC with DOE. CC revealed diffuse interstitial prominence and echo was WNL. She rapidly improved with S. C#3 63 yr W was Di with 2.3 cm, TN, invasive duct carcinoma of left breast. NC with DD AC followed by P was started. After 2 nd infusion of P, she developed hypoxia and cough; CC revealed diffuse groundglass opacities throughout lungs bilaterally, suggestive of HSP. She rapidly improved with S. Results: All 3 cases occurred in non-smoking pts without known lung/cardiac disease, treated with PF on day 2 of each cycle. Pts had abnormal CCs, were afebrile and responded quickly to steroids. Published DD experience (Citron et al) uses daily filgrastim (F), not the pegylated form which our pts received. We believe that HSP in these pts may be related to long acting growth factor stimulation of white cells and causing reversible HSP. Conclusions: Future prospective studies on taxanes using DD regimens should include a randomized design where pts given PF are compared to pts who receive F. No significant financial relationships to disclose.
Frequency and Prognostic Impact of Complex Chromosomal Aberrations in Patients with Primary Myelodysplastic Syndromes and Del(5q).
Authors: Zuzana Zemanova, Kyra Michalova, Jana Brezinova, Libuse Lizcova, Silvia Izakova, Dagmar Bystricka, Iveta Sarova, Adela Berkova, Magda Siskova, Radana Neuwirtova, Olga Cerna, Jaroslav Cermak
Journal: Blood (2009)
Effects of continuous positive airway pressure on energy balance regulation: a systematic review
Authors: Ari Shechter
Journal: European Respiratory Journal (2016)

Obesity is both a cause and a possible consequence of obstructive sleep apnoea (OSA), as OSA seems to affect parameters involved in energy balance regulation, including food intake, hormonal regulation of hunger/satiety, energy metabolism and physical activity. It is known that weight loss improves OSA, yet it remains unclear why continuous positive airway pressure (CPAP) often results in weight gain. The goal of this systematic review is to explore if and how CPAP affects the behaviour and/or metabolism involved in regulating energy balance. CPAP appears to correct for a hormonal profile characterised by abnormally high leptin and ghrelin levels in OSA, by reducing the circulating levels of each. This is expected to reduce excess food intake. However, reliable measures of food intake are lacking, and not yet sufficient to make conclusions. Although studies are limited and inconsistent, CPAP may alter energy metabolism, with reports of reductions in resting metabolic rate or sleeping metabolic rate. CPAP appears to not have an appreciable effect on altering physical activity levels. More work is needed to characterise how CPAP affects energy balance regulation. It is clear that promoting CPAP in conjunction with other weight loss approaches should be used to encourage optimal outcomes in OSA patients.
DOES A ‘PREVENT INJURY AND ENHANCE PERFORMANCE’ PROGRAMME (PEP) CHANGE THE NEUROMUSCULAR CONTROL IN YOUNG FEMALE ACROBATIC GYMNASTS?
Authors: EC Ross, P Thawley
Journal: British Journal of Sports Medicine (2016)

Aims The primary aim of this interventional study was to identify if a PEP1 is an effective neuromuscular training intervention to change neuromuscular control (NMC) of the lower limb in young female acrobatic gymnasts. Secondary aims were to identify if the gymnast's perceived a change in their own strength, physical sporting ability (PSA), self-esteem or physical self-worth (PSW) following this neuromuscular training method. Methods Fifty-four female acrobatic gymnasts, mean age 11.43 years (±2.96 range 7–18 years), height 1.44 (±0.16 SD) metres, mean weight 37.4 kg (±13.35 SD), were recruited. All participants were assessed through 2-dimensional video analysis using the Qualitative Analysis of Single Leg Squat Scoring tool2 (QASLS) and The Children and Youth Self-Perception Questionnaire3 (CY-PSPP). Outcome measures were completed pre- and post- an eight week PEP intervention. The PEP was completed up to three times a week, prior to standard acrobatic training, within the competitive season. Results Post-interventional analysis observed a significant improvement in the QASLS score on both the right (p=0.001) and left lower limb (p=0.001) of female gymnasts. The CY-PSPP questionnaire showed significant improvement in gymnast's perception of their strength (p=0.013), PSA (p=0.002) and self-esteem (p=0.013). No significance was observed in PSW (p=0.164). Conclusions An 8-week PEP showed a significant effect in increasing young female acrobatic gymnasts NMC whilst performing a single leg squat. The PEP, as a method of neuromuscular training, demonstrated significant improvement in gymnast's self-perception of strength, PSA and self-esteem. Gymnastics is a sport dominated by childhood and adolescent age groups. Effective injury prevention strategies are vital to protect the health of young gymnasts. These results demonstrate that a PEP incorporating neuromuscular training interventions during childhood and pre-adolescence can positively improve young female gymnasts' NMC.
Different IGH Rearrangement and Somatic Hypermutation Patterns in Hairy-Cell Leukemia, Hairy-Cell Leukemia Variant and Splenic Marginal Zone Lymphoma.
Authors: Sarah L. Hockley, Stavroula Giannouli, Alison Morilla, Gareth J. Morgan, Estella Matutes, David Gonzalez
Journal: Blood (2007)
Phase II trial of GM-CSF in women with asymptomatic müllerian cancer
Authors: M. Roche, U. Matulonis, C. Krasner, R. Penson, N. Horowitz, A. Berkenblit, M. Findley, J. Lee, N. Horick, M. V. Seiden
Journal: Journal of Clinical Oncology (2006)

5081 Background: GM-CSF is a recombinant human cytokine, which increases the proliferation of granulocytes and monocytes. Experience with this agent, including adjuvant studies in melanoma, vaccine-based studies using autologous tumor vaccines that secrete human GM-CSF, and studies in prostate cancer using GM-CSF have all suggested that GM-CSF might provide anti-tumor activity in a subset of cancer patients. Methods: Open label phase II study performed in asymptomatic patients with recurrent mullerian malignancy without an indication for immediate systemic chemotherapy. Patients could have measurable or evaluable disease (defined as CA-125 &gt;35 U/ml or 2 successively rising values with the most recent 3x the nadir value.) GM-CSF 250 mcg/m 2 was administered subcutaneously on days 1–14 of a 28-day cycle. Monthly follow-up included interim history, physical exam and CA-125, with radiologic evaluation q 3 months. Results: Enrollment to this cohort is complete. Thirty-five women with a median age of 60 were enrolled; data are available on 33:30 women with ovarian and 3 with primary peritoneal cancers. To date 31 women are evaluable for response. Best overall response of patients who have completed the study includes 6 patients with stable disease (18%). Median time to treatment termination (TTT) was 76 days. Four patients remain on study, 2 with SD &gt;6 months. Toxicity was generally mild, including injection site reaction, fatigue, and bone pain, however 2 patients experienced excessive toxicity and withdrew consent. There were 3 bowel obstructions thought related to disease but contribution of drug could not be ruled out. After 14 days of GM-CSF, CA-125 dropped in 23 of 33 women (70%) from their baseline on study value (median change -23%, range −48 to +158%). The magnitude of CA-125 drop during the first two weeks of therapy was significantly and positively correlated with day 15 WBC (p = 0.04.) Conclusions: GM-CSF is well tolerated and frequently associated with a decline in CA-125 that is correlated with leukocytosis. Although median TTT for the entire group is modest, a subset of women have had prolonged stable disease. Strategies to maintain and titrate leukocytosis are now being explored in a separate cohort. No significant financial relationships to disclose.
Treatment Emergent Mutations in NAEβ Confer Resistance to the NEDD8-Activating Enzyme Inhibitor MLN4924 in Pre-Clinical AML and DLBCL Models
Authors: Michael Milhollen, Michael Thomas, Tary Traore, Usha Narayanan, Jessica Riceberg, Todd Sells, Ben Amidon, Mark Manfredi, Neil Bence, James Brownell, Larry Dick, Erik Koenig, James Gavin, Peter G Smith
Journal: Blood (2011)
Interactions Between Megakaryocytes and Tumour Cells at the Bone Marrow Vascular Stem Cell Niche Promote Tumour Growth and Metastasis.
Authors: Bethan Psaila, Anna Podolanczuk, Simon Lavotshkin, John Lawrence, Rosandra Kaplan, Selena Granitto, James B. Bussel, Naresh Kikkeri, Irene Roberts, David Lyden
Journal: Blood (2009)
Disulfiram, an Clinically Used Anti-Alcoholism Drug Has the Potential to Target Leukemia Stem and Progenitor Cells in a Copper-Dependent Manner
Authors: Bing Xu, Shiyun Wang, Feili Chen, Pengcheng Shi, Jie Zha, Yanyan Zhang, Xutao Guo, Weiguang Wang
Journal: Blood (2012)
Recombination of Endogenous TCR Chains with Retrovirally Introduced TCR Chains Can Result in Mixed T Cell Receptor Dimers Harbouring Harmful Alloreactivity
Authors: Marleen M Van Loenen, Renate de Boer, Gerdien L Volbeda, Avital L Amir, Renate S. Hagedoorn, Roelof Willemze, J.H. Frederik Falkenburg, Mirjam H.M. Heemskerk
Journal: Blood (2008)
Biomarkers and In Vivo Responses to the BH3 Mimetic, ABT-263, in Patients (pts) with Chronic Lymphocytic Leukemia (CLL).
Authors: Seong Lin Khaw, David C. Huang, Simon He, John F Seymour, Dennis Carney, Kylie D. Mason, Brenda Chyla, Elizabeth Litvinovich, Evelyn McKeegan, Andrew Krivoshik, Sari Enschede, Rod Humerickhouse, Andrew W. Roberts
Journal: Blood (2009)
Physiological Uptake in the Pancreatic Head on Somatostatin Receptor Scintigraphy Using [111In-DTPA]Octreotide
Authors: Tessa Brabander, Jaap Teunissen, Dik Kwekkeboom
Journal: Clinical Nuclear Medicine (2016)

Physiological uptake in the uncinate process or pancreatic head has been described with Ga-labeled PET tracers for somatostatin receptor imaging. In-DTPA-octreotide is the only registered radiopharmaceutical for the imaging of neuroendocrine tumors. We studied the uptake in this region of the pancreatic head on somatostatin receptor scintigraphy (SRS) using In-DTPA-octreotide in a large group of patients. Furthermore, known physiological and clinical characteristics are discussed in an attempt to elucidate this phenomenon.Four hundred seven patients underwent SRS using In-DTPA-octreotide in our department in 2014. After excluding patients with a known malignancy in or close to the pancreas, as well as all scans without SPECT/CT of the upper abdomen, we reviewed 178 scans in total. The uptake was graded on a 4-point scale that correlates the uptake in the pancreatic head to physiological uptake in the liver.Uptake in the region of the pancreatic head, including the uncinate process, was seen in 46 (26%) of 178 patients on SPECT/CT and in 12 patients (7%) on planar imaging. On SPECT/CT, uptake was lower than the liver in 26 patients (15%), equal to the liver in 17 patients (10%), and higher than the liver in 3 patients (2%). In patients with diabetes mellitus (DM), the incidence of uptake in the pancreatic head was 50% on SPECT/CT.Physiological uptake in the pancreatic head is seen on SPECT/CT with In-DTPA-octreotide in 26% of patients, and the incidence is doubled in patients with DM. Previous case reports showed uptake in the pancreatic head due to histologically proven pancreatic polypeptide (PP) cell hyperplasia. Also, patients with DM have elevated serum PP concentrations, which is likely due to PP cell hyperplasia. Because 90% of PP cells are present in the pancreatic head, PP cell hyperplasia is the most likely explanation for visualization of the pancreatic head on SRS in a substantial number of patients.
PET/CT With 68Ga-DOTA-TATE for Diagnosis of Neuroendocrine
Authors: Ofer Nathan Gofrit, Stephen Frank, Amichay Meirovitz, Hovav Nechushtan, Marina Orevi
Journal: Clinical Nuclear Medicine (2016)

Castrate-resistant prostate cancer (CRPC) often shows histological evidence of neuroendocrine differentiation (NED). To evaluate the extent of NED in patients with CRPC, we used PET/CT with Ga-[DOTA-Tyr]-octreotate (Ga-DOTA-TATE), a somatostatin analog that binds somatostatin receptor 2 with high affinity. This radiotracer is used in imaging of neuroendocrine tumors.Twelve patients (mean age, 65 [SD, 12] years) with CRPC were studied. Their mean prostate-specific antigen level at scanning was 85.6 (SD, 144.6) ng/mL. PET/CT images were obtained after the injection of 120 to 200 MBq of Ga-DOTA-TATE.All participants had at least 1 blastic metastasis demonstrating uptake of Ga-DOTA-TATE (mean SUVmax of 5.3 [SD, 2.3]). In 6 patients, moderately high to high uptakes (SUVmax, >5) were seen. Patients with multiple bone metastases had a significantly higher SUVmax compared with patients with few metastases (mean of 5.8 vs 3.8, P = 0.05). In 4 patients, lytic bone lesions or lymph node metastases also showed uptake of the tracer (mean SUVmax of 7.2 [SD, 3.2]). Uptake of the radiotracer was also observed in bones showing normal architecture in CT, suggesting that NED cells appear early during metastases development.Uptake of Ga-DOTA-TATE is a common finding in metastases of CRPC patients, suggesting that NED is frequent in these patients. In half of the patients, widespread uptake of Ga-DOTA-TATE was observed. This suggests that the possibility of treating selected CRCP patients with anti-neuroendocrine tumor therapies should be explored and that Ga-DOTA-TATE scanning could have a role in predicting the efficacy of these treatments.
An African American Man with Diffuse Erythematous Papules
Authors: Jewell V. Gaulding, Sherry Yang, Henry W. Lim
Journal: JAMA Dermatology (2016)

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Simplified prostate lesion grading for magnetic resonance imaging and improved cancer detection at fusion-targeted prostate biopsy.
Authors: Steven V. Kardos, Cayce Nawaf, Richard Fan, Daniel Cornfeld, Jeffrey Weinreb, Peter Schulam, Preston Sprenkle
Journal: Journal of Clinical Oncology (2015)

69 Background: Prostate cancer (PCa) is the most common solid organ malignancy in men and the second leading cause of cancer related death; however, it is the only tumor that is diagnosed by a non-targeted sampling method. Fusion targeted prostate biopsy is emerging as a more accurate way to detect PCa. The use of a multiparametric MRI (MP-MRI) with an endorectal coil (ERC) has traditionally been used, though the benefit for detection with ERC is controversial. In addition, there is significant heterogeneity in classification of MRI-identified lesions. We provide an initial report with fusion biopsy without an ERC and utilizing a simplified 3-point Likert scale for grading prostatic lesions. Methods: Patients underwent MRI-USG fusion biopsy for elevated PSA, abnormal DRE, or prior negative biopsy. Lesions visible on MRI were outlined in 3D and assigned increasing cancer suspicion levels using a simplified 3-point Likert scale by dedicated pelvic radiologists. The Artemis biopsy tracking system was used to fuse the MRI with real-time ultrasound. Using the 3D model, a 12-core systematic biopsy, as well as a targeted biopsy of suspicious areas, was performed by a urologist (PS). Results: 190 patients underwent MRI and fusion biopsy between 12/2012 and 8/2014. The overall cancer detection rate (CDR) for systematic biopsy was 52.3% and the CDR for fusion biopsy was 55.0%. However, the CDR for clinically significant PCa with systematic biopsy was 28.7% and for targeted biopsy was 43.8% (p=0.02). Evaluation of cancer suspicion level for each ROI revealed that patients with high suspicion scores had a higher overall CDR (p&lt;0.0001) and higher risk of detecting clinically significant cancer under the Cochran Armitage Trend test (p=0.0001). Conclusions: MRI-USG fusion prostate biopsy using MP-MRI without an ERC and a read using a simplified 3-point Likert scale demonstrate improved detection of clinically significant PCa compared to a systematic 12 core TRUS biopsy, and further demonstrate that lesion suspicion correlates with CDR. CDR and lesion stratification are comparable to the published literature when using methodologies that may be more practical in a larger number of medical centers.
IFN-γ Induced by PHA Stimulation as New Marker for Gvhd Prediction in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Enrico Morello, Vladia Monsurrò, Elisabetta Pagani, Irene Cavattoni, Silvia Coin, Giuseppe Tridente, Clara Larcher, Sergio Cortelazzo
Journal: Blood (2008)