tbuckley/cabot-search huggingface dataset:
Change in treatment as result of FDG-PET and CT in clinically stage III melanoma patients: A prospective study in 221 patients
Authors: E. Bastiaannet, T. Wobbes, S. Meijer, H. J. Hoekstra
Journal: Journal of Clinical Oncology (2008)

9069 Background: An important part in the treatment planning for metastatic melanoma is an evaluation of the presence or absence of distant melanoma metastases. However, melanoma has the well-known feature to spread to unusual sites and the presence of multiple metastases is usually a contraindication for surgery. The aim of this study was to assess how treatment changed as result of the FDG-PET and spiral CT in patients clinically stage III melanoma. Methods: All consecutive patients older than 18 years with palpable, histology/cytology proven lymph node metastases of melanoma referred to the five participating hospitals between July 2003 and July 2007 for examination with FDG-PET and CT were prospectively included in this study. All patients were considered candidates for further surgical intervention in the form of a regional lymph node dissection. Performed treatment was recorded to define a change in treatment plan. Results: Overall, 221 patients were included in the five hospitals. More than half the patients were male, median age was 57.9 (range 23.2–93.1) years. The primary melanoma was mostly located on the lower extremities (35.6%) or trunk (35.6%). PET and CT were comparable in detecting liver and abdominal metastases, CT detected more lung metastases and PET detected more bone and skin metastases. Treatment changed in 41 patients (18.6%), mostly as result of both scans (n=34), or PET alone (n=5) or CT alone (n=2). In 28 patients treatment changed to chemotherapy, 6 patients received a superficial lymph node dissection for local control while 3 patients received two lymph node dissections as result of other lymph node metastases that were detected. Conclusions: In conclusion, treatment changed in 19% of the melanoma patients with palpable lymph node metastases, mostly as result of both scans. The identification of metastatic disease did not always change the clinical management of the patients. The PET scan, with the CT scan as a good alternative are indicated in staging of melanoma patients with palpable lymph node metastases. No significant financial relationships to disclose.
570. Efficient In Vitro Expansion and Gene Correction of Dystrophic Mouse Muscle Stem Cells
Authors: Mohammadsharif Tabebordbar, Jason Cheng, Amy Wagers
Journal: Molecular Therapy (2015)

Duchenne Muscular Dystrophy (DMD) is a progressive muscle wasting disease caused by mutations in the DYSTROPHIN gene. Gene correction and autologous transplantation of muscle stem cells (i.e., satellite cells) presents a promising therapeutic approach for restoring DYSTROPHIN expression to muscle fibers in these patients; however the low frequency of satellite cells in adult muscle is an obstacle for isolating sufficient numbers of cells for engraftment. To address this issue, we have sought culture conditions that would support the ex-vivo expansion of satellite cells and potentially provide more cells for transplantation. We found that forskolin, an adenylyl cyclase activator, dramatically expanded mouse satellite cells in culture. Forskolin-treated cultured cells retained the immunophenotypic characteristics of engraftable satellite cells, and transplantation of compound-treated cells into dystrophic muscle yielded a significantly higher level of engraftment compared to control cells. Forskolin also dramatically expands satellite cells from mdx mouse model of DMD in culture. As a proof of concept for a combined gene and cell therapy approach for treating DMD, we targeted the mutated Dystrophin locus in ex-vivo expanded forskolin treated dystrophic satellite cells using CRISPR/Cas9 gene editing technology and enriched for the targeted cells using an endogenous fluorescent reporter system. Expansion and gene correction of muscle satellite cells in culture as described here provides the possibility of improving combined gene and cell-based therapies for neuromuscular disorders.
PWE-046 Factors that influence outcome of patients with severe upper gastrointestinal variceal bleeding. A single centre experience
Authors: M A Al-Freah, A Gera, S Martini, D Shawcross, R D Abeles, N Taylor, G Auzinger, P Harrison, J Devlin, M A Heneghan, N D Heaton, W Bernal, J A Wendon
Journal: Gut (2010)

<h3>Introduction</h3> Upper gastrointestinal variceal bleeding (UGIVB) is associated with high mortality rate. <h3>Aim</h3> To determine predictors of outcome (42-day survival and 5-day rebleeding rate) of patients admitted with severe UGIVB. <h3>Methods</h3> Retrospective study of all patients admitted to liver intensive therapy unit (LITU) in our centre with severe UGIVB 01/01/2000 to 31/03/2008. <h3>Results</h3> 177 patients, 157 analysed. Male 90/157 (57%). Median age was 49 years (IQR 39–57). Alcohol related liver disease 83/157 (53%). Cirrhosis was confirmed in 136 patients (87%). Median MELD was 15 (IQR 11–20). All patients referred 126/177 (71%) failed endoscopic haemostasis at referring hospital (RH). Median RBC transfusion at RH was 9 units (IQR 6–15) with 80% had Sengstaken-Blakemore tube inserted prior to transfer. Median LITU length of stay (LOS) 6 days (IQR 3–15). Median hospital stay was 24 days (IQR 13–40). LITU survival was 70% (133/157). Hospital survival 61% (96/157). Survival at 42 days was 60% (94/157). Factors determining 6-week survival, survivors to non-survivors, were Day (D) 1 MELD (13 vs 19), D5 MELD (13 vs 25), ▵ (D5-D1) MELD (0 vs 4), D1 UKELD (Na incorporated MELD) (53 vs 57), D5 UKELD (52 vs 56) and APACHE II score (16 vs 24), p&lt;0.0001 (all). AUROC curve analysis showed the following prognostic indicators performed well: D1 MELD=0.75, D5 MELD=0.84, ▵MELD=0.74 and D1 APACHE II score=0.78. Median number of endoscopies was 2 (IQR 1–3). Endoscopy performed within 24 h of LITU admission in 94%. Bleeding source was oesophageal varices 96/145 (66.2%), gastric varices 12/145 (8.3%) and ectopic varices 2/145 (1.4%). Active bleeding identified in 93/144 (65%). Five day rebleeding rate was 13% (20/153). Four had failure of control of bleeding. There was no significant difference in hospital survival (62% vs 65%), LITU survival (72% vs 65%), LITU LOS in days (6 vs 8) and hospital LOS in days (24 vs 32) comparing those who achieved primary haemostasis to rebleeders (P=NS). Admission haemoglobin, platelet count, transfusion requirement, MELD and UKELD did not predict rebleeding (p=NS). TIPSS was performed on 10%. Seven patients (35%) of those who rebled within 5 days had TIPSS. TIPSS insertion did not influence hospital survival (p=0.46). <h3>Conclusion</h3> Outcome of severe UGIVB is determined by severity of liver disease and organ failure assessed by MELD/UKELD and APACHE II, respectively. However, these factors did not predict rebleeding. Endoscopic haemostasis was achieved in the majority of patients. TIPSS did not influence outcome in this selected cohort of UGIVB.
Not All Positive Interim PET/CT Scans Are Reliably Predictive for Progression Free Survival in Hodgkin Lymphoma (HL) Patients. A Proposed Model for a Functional Scoring Scale.
Authors: Eldad J. Dann, Ada Tamir, Ron Epelbaum, Irit Avivi, Menachem Ben-Shachar, Diana Gaitini, Jacob M. Rowe, Rachel Bar-Shalom
Journal: Blood (2008)
Temporal Dynamics of Tumor-Microenvironment Interaction and Treatment Responses Revealed through Time-Lapse Compartment-Specific Bioluminescence Imaging: Translational implications
Authors: Eugen Dhimolea, Emily King, Efstathios Kastritis, Douglas W. McMillin, Jake E. Delmore, Joseph M. Negri, Hannah M. Jacobs, Catriona A. Hayes, Michal Sheffer, Yiguo Hu, Subhashis Sarkar, Richard W.J. Groen, Megan A. Bariteau, Blake T. Aftab, Constantine S. Mitsiades
Journal: Blood (2014)
The Movement of Streptococcal Infection in Otsu City : Proceedings of the IV Conference on Prevention for Rheumatic Fever and Rheumatic Heart Disease, January 1979, Kyoto
Authors: Seiichi Kawakita, Junzo Inoue, Tsune Takeuchi, Yoshio Umehara, Toyohiko Onishi
Journal: Circulation (1980)

The throat cultures were collected on swabs from total number of 3,599 of first grade children of elementary schools in Otsu City in 1978. Beta-hemolytic streptococci were isolated from 628 of 3,599 children (17.4%). Group A strains were found in 403 of 628 children (64.2%). Thus the frequency of recovery of group A streptococci from the children was 11.2% in this study. The size of tonsils in children with positive cultures for group A streptococci and negative response of ASO was larger than tonsils of children with negative cultures for group a strains and negative ASO response, and were smaller than the tonsils of children with positive cultures for group A strains and with positive ASO response. On the 20th day after oral administration of 400,000 units of penicillin derivative, group A strains were eradicated from throats in 76.2% of the treated children.
The Combination of Cyclophosphamide, Velcade and Dexamethasone (CVD) Induces High Response Rates with Minimal Toxicity Compared to Velcade Alone (V) and Velcade Plus Dexamethasone (VD).
Authors: Faith E. Davies, Ping Wu, M. Srikanth, Matthew W. Jenner, Sharon Dines, Radovan Saso, Gareth J. Morgan
Journal: Blood (2006)
CC-008 Please see this man with abnormal liver function tests
Authors: J A Saunders, T R Smith, A E Drury, N A Davis, P R McCrudden
Journal: Gut (2010)

<h3>Introduction</h3> A 45-year-old man presented with a 2-day history of jaundice and severe epigastric pain radiating through to his back. He also complained of nausea and vomiting. He noted his urine to be dark and his stools pale but denied having pruritis. He drank 30 units of alcohol a week and had returned from mainland Spain 5 days prior to his illness. There was no previous history of jaundice or additional risk factors for chronic liver disease. He was on no regular medications. His only significant past medical history was a laparoscopic cholecystectomy performed 8 months previously due to an attack of cholecystitis. <h3>Methods</h3> Initial blood tests demonstrated a mildly raised bilirubin and amylase but a marked transaminitis (ALT 2073 iu/l, normal range 0–35 iu/l). Twenty-four hours after admission he deterioratd with sepsis, renal failure, thrombocytopaenia and a microangiopathic anaemia. Imaging demonstrated common bile duct stones causing biliary obstruction and pancreatic inflammation. He was treated for his microangiopathic anaemia and as part the management of pancreatitis underwent an early therapeutic ERCP to provide biliary drainage. <h3>Results</h3> The prevalence of common bile duct stones (CBDS) in patients with symptomatic gallstones is quoted to lie between 10 and 20%.1 In patients who are not jaundiced and have a normal trans-abdominal ultrasound the prevalence is said to be &lt;5%.2 The natural history of CBDS is not well understood but if they do become symptomatic the consequences are often serious. He was assessed as low risk for CBDS and as suggested by current BSG guidelines did not have any additional biliary imaging.3 This patient had an atypical presentation of a relatively common condition and subsequently developed a very rare complication. He required a prolonged critical care admission to support the management of multi-organ failure, which involved the expertise of a closely coordinated multidisciplinary team. <h3>Conclusion</h3> The traditional teaching that an ALT &gt;1000 iu/is due to drugs, viral hepatitis or ischaemia is a good rule of thumb. However, it is not a “golden rule” and when the clinical picture does not fit, the differential diagnosis needs to be widened. This case highlights the difficulties, complexity and spectrum of clinical conditions which present with abnormal liver function tests.
Immunogenicity of the Tetravalent Protein-Conjugated Meningococcal Vaccine in Recipients of Related and Unrelated Allogeneic Hematopoietic Cell Transplants (HCT)
Authors: Michelle Mahler, Nancy A Kernan, Farid Boulad, Susan Prockop, Andromachi Scaradavou, Esperanza B Papadopoulos, Heidi Abendroth, Anne Casson, Catherine Copeland, Maura Murphy, Joanne Torok-Castanza, Richard J. O’Reilly, Trudy N. Small
Journal: Blood (2008)
Abstract 2599: Discovery and pharmacological characterization of the second generation of Btk inhibitors with improved target selectivity and enhanced in vivo efficacy
Authors: Jiayin Zhang, Dong Liu, Ru Shen, Yinfa Yan, Liuqing Yang, Minsheng Zhang, Jun Feng, Beibei Fu, Jerry Hu, Biao Lu, Hong Wan, Lei Zhang, Weikang Tao, Lianshan Zhang, Jingsong Cao
Journal: Cancer Research (2015)

Abstract Bruton's tyrosine kinase (Btk) is an essential component of the B-cell receptor (BCR) signaling pathways regulating survival, activation, proliferation, and differentiation of B lymphocytes. The first Btk inhibitor, Ibrutinib, has demonstrated a significant clinical efficacy in a variety of B-cell malignancies. Through structure-guided approach, we have discovered two series of novel and potent Btk inhibitors, represented by EBI-1266 and EBI-1367, respectively. Both of these compounds showed high potency in inhibiting Btk kinase activity and growth of a number of aggressive lymphoma cell lines driven by aberrant BCR signaling, with IC50 value within low nanomolar range. Mechanistic studies examining BCR signaling pathway in related B cell lymphoma cell lines revealed that both EBI-1266 and EBI-1367 potently inhibited Btk phosphorylation and downstream Erk phosphorylation, similar to Ibrutinib. Furthermore, each compound showed unique and significant superiority over Ibrutinib: EBI-1266 had a cleaner selectivity profile against a panel of kinases with a cysteine residue in the conserved catalytic domain, and EBI-1367 exhibited &amp;gt;10-fold higher in vivo exposure in multiple preclinical species. In a tumor xenograft mouse model where tumor growth is dependent on Btk activity, both EBI-1266 and EBI-1367 showed significant oral anti-tumor activities, with EBI-1367 being more efficacious than Ibrutinib, consistent with a higher exposure of EBI-1367 in both blood and tumor tissues. No evidence of overt toxicities was observed in rodents with prolonged oral administration for two weeks with doses at least 3-fold above a highly efficacious dose. In summary, the pharmacological profiles of EBI-1266 and EBI-1367 indicate that these compounds have a great potential to become the next generation of Btk inhibitors, offering advantages in pharmaceutical development, enhanced in vivo efficacy and reduced toxicities. We are currently performing IND-enabling studies aiming to initiate phase I clinical trials for these Btk inhibitors. Citation Format: Jiayin Zhang, Dong Liu, Ru Shen, Yinfa Yan, Liuqing Yang, Minsheng Zhang, Jun Feng, Beibei Fu, Jerry Hu, Biao Lu, Hong Wan, Lei Zhang, Weikang Tao, Lianshan Zhang, Jingsong Cao. Discovery and pharmacological characterization of the second generation of Btk inhibitors with improved target selectivity and enhanced in vivo efficacy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2599. doi:10.1158/1538-7445.AM2015-2599
When, What, and Why of Perioperative Treatment of Potentially Curable Pancreatic Adenocarcinoma
Authors: Kimberly Perez, Thomas E. Clancy, Joseph D. Mancias, Michael H. Rosenthal, Brian M. Wolpin
Journal: Journal of Clinical Oncology (2017)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 64-year-old woman with a history of hypertension and type 2 diabetes had been in her usual state of health until she developed symptoms of diarrhea, abdominal bloating, and discomfort in the midepigastrium. Evaluation with a contrast-enhanced abdominopelvic computed tomography (CT) scan demonstrated a mass in the pancreatic body that was approximately 3.1 cm × 2 cm × 2.1 cm in size with abutment of the portal vein–superior mesenteric vein confluence for less than 180°. The confluence was narrowed but without thrombosis. No tumor–vessel interface was noted at the superior mesenteric artery, celiac artery, or common hepatic artery. Several peripancreatic lymph nodes were observed that measured up to 11 mm × 5 mm. No evidence for distant spread of disease was identified. An upper endoscopy with endoscopic ultrasound was performed and fine-needle aspirates of the pancreas mass were positive for malignant cells that were consistent with adenocarcinoma. Chest CT scan without intravenous contrast demonstrated no evidence of metastatic disease. The patient came to the clinic to discuss management of her newly diagnosed malignancy.
Interim Positron Emission Tomography-Computed Tomography (PET-CT) Is Predictive of Post-Therapy Outcome in High Grade Transformation of Low Grade Lymphoproliferative Disorders
Authors: Louise Imlay-Gillespie, David Simon Kliman, Kelly Wong, Christopher Arthur, Luke Coyle, Keith Fay, Ian H. Kerridge, Naomi Mackinlay, Stephen Mulligan, William Stevenson, Christopher M Ward, Matthew Greenwood
Journal: Blood (2015)
Chemotherapy-related complication burden in patients with metastatic breast cancer in a real-world setting.
Authors: S. A. Hurvitz, D. Lalla, A. Guerin, D. Latremouille-Viau, A. P. Yu, E. Q. Wu, M. Brammer
Journal: Journal of Clinical Oncology (2011)

e11101 Background: To assess the rate of chemotherapy-related complications in patients with metastatic breast cancer (mBC). Methods: Patients with mBC (including all biological subtypes) treated with chemotherapy and/or HER2-targeted agents were selected from the PharMetrics Integrated Database (2004-2009). Episodes of treatment (defined as a course of single-agent or combination) ≥30 days were identified. Rates of episodes associated with claims for complications were reported. Results: 1,551 patients (mean age 57±12]) with 3157 treatment episodes met the inclusion criteria. Out of the 3,157 treatment episodes, 1181 (37%) were combination regimens with 311 (26%) episodes of combination of chemotherapy with an anti-hormone agent. Patients had on average 2 episodes with a mean length of 131 days. The most frequently used agents were anti-HER2 (i.e., trastuzumab and lapatinib), docetaxel, paclitaxel, capecitabine, gemcitabine, vinorelbine, doxorubicin, bevacizumab, albumin-bound paclitaxel, and cyclophosphamide. Complication rates for the most common adverse events in regimens containing an anti-HER2 agent, docetaxel and paclitaxel are reported. Conclusions: The most frequent complications during an episode of mBC chemotherapy treatment were anemia, nausea/vomiting, bilirubin elevation, leukopenia, and infection. The impact of the high rates of these complications on treatment duration and compliance may lead to suboptimal clinical outcomes and higher costs. All episodes of treatment Anti-HER2-based regimen1 Docetaxel-based regimen2,3 Paclitaxel-based regimen2,3 Number of patients 1551 510 228 175 Number of episodes of treatment 3157 1157 264 188 Average by patient [median] 2.0 [2.0] 2.3 [2.0] 1.2 [1.0] 1.1 [1.0] Average duration (days) [median] 131 [91] 158 [104] 118 [88] 115 [78] Number of episodes with complications Anemia 51% 51% 55% 52% Bilirubin elevation 26% 29% 22% 31% Infection 19% 20% 23% 14% Leukopenia 25% 18% 36% 23% Nausea/vomiting 44% 41% 51% 45% 1Monotherapy or combination. 2Excluding HER2-agents. 3Monotherapy or combination with anti-hormone therapy.
Complementing Operating Room Teaching With Video-Based Coaching
Authors: Yue-Yung Hu, Laura M. Mazer, Steven J. Yule, Alexander F. Arriaga, Caprice C. Greenberg, Stuart R. Lipsitz, Atul A. Gawande, Douglas S. Smink
Journal: JAMA Surgery (2016)

<h3>Importance</h3> Surgical expertise demands technical and nontechnical skills. Traditionally, surgical trainees acquired these skills in the operating room; however, operative time for residents has decreased with duty hour restrictions. As in other professions, video analysis may help maximize the learning experience. <h3>Objective</h3> To develop and evaluate a postoperative video-based coaching intervention for residents. <h3>Design, Setting, and Participants</h3> In this mixed methods analysis, 10 senior (postgraduate year 4 and 5) residents were videorecorded operating with an attending surgeon at an academic tertiary care hospital. Each video formed the basis of a 1-hour one-on-one coaching session conducted by the operative attending; although a coaching framework was provided, participants determined the specific content collaboratively. Teaching points were identified in the operating room and the video-based coaching sessions; iterative inductive coding, followed by thematic analysis, was performed. <h3>Main Outcomes and Measures</h3> Teaching points made in the operating room were compared with those in the video-based coaching sessions with respect to initiator, content, and teaching technique, adjusting for time. <h3>Results</h3> Among 10 cases, surgeons made more teaching points per unit time (63.0 vs 102.7 per hour) while coaching. Teaching in the video-based coaching sessions was more resident centered; attendings were more inquisitive about residents' learning needs (3.30 vs 0.28,<i>P</i> = .04), and residents took more initiative to direct their education (27% [198 of 729 teaching points] vs 17% [331 of 1977 teaching points],<i>P</i> &lt; .001). Surgeons also more frequently validated residents' experiences (8.40 vs 1.81,<i>P</i> &lt; .01), and they tended to ask more questions to promote critical thinking (9.30 vs 3.32,<i>P</i> = .07) and set more learning goals (2.90 vs 0.28,<i>P</i> = .11). More complex topics, including intraoperative decision making (mean, 9.70 vs 2.77 instances per hour,<i>P</i> = .03) and failure to progress (mean, 1.20 vs 0.13 instances per hour,<i>P</i> = .04) were addressed, and they were more thoroughly developed and explored. Excerpts of dialogue are presented to illustrate these findings. <h3>Conclusions and Relevance</h3> Video-based coaching is a novel and feasible modality for supplementing intraoperative learning. Objective evaluation demonstrates that video-based coaching may be particularly useful for teaching higher-level concepts, such as decision making, and for individualizing instruction and feedback to each resident.
Genetic Allelic Variation in the p53 DNA Repair Pathway Constitute a Risk Factor for Long-Term Survival in Hematopoietic Stem Cell Transplantation
Authors: Stige. Bojesen, Mari Malkki, Ted Gooley, Lue Ping Zhao, Annamalai Selvakumar, Stephen R Spellman, Effie W Petersdorf, John A. Hansen, Bo Dupont
Journal: Blood (2008)
Analysis of Pre-Transplant Therapy with Brentuximab Vedotin for Relapsed/Refractory Hodgkin Lymphoma on Outcomes of Reduced Intensity Conditioned Allogeneic Hematopoietic Cell Transplantation
Authors: Baldeep Wirk, Barry E. Storer, David G Maloney, Ajay K Gopal, Ryan D Cassaday, Rachel Salit, Paul V. O'Donnell, Brenda M. Sandmaier, Mary E.D. Flowers
Journal: Blood (2015)
Salvage Allogeneic Hematopoietic Stem Cell Transplantation for Primary Graft Failure in Children
Authors: Motohiro Kato, Kimikazu Matsumoto, Ritsuro Suzuki, Hiromasa Yabe, Masami Inoue, Hisato Kigasawa, Jiro Inagaki, Hisamichi Tauchi, Hisashi Sakamaki, Keisei Kawa, Koji Kato, Takahiro Fukuda
Journal: Blood (2012)
Establishment of a NOD/SCID/γc−/−-Dependent Lymphoid Leukemia Cell Line, D593, with Novel RUNX1-LAF4 Fusion Gene.
Authors: Akihiro Abe, Manabu Ninomiya, Shizuka Imagama, Momoko Suzuki, Fumihiko Hayakawa, Akira Katsumi, Hitoshi Kiyoi, Seiji Kojima, Tomoki Naoe
Journal: Blood (2006)