tbuckley/cabot-search huggingface dataset:
Mesenteric lymphadenopathy in patients with germ cell tumor.
Authors: Hooman Djaladat, Craig R. Nichols, Siamak Daneshmand
Journal: Journal of Clinical Oncology (2012)

347 Background: Mesenteric lymphadenopathy may be secondary to inflammatory, infectious or tumoral pathologies. The most common malignancies causing mesenteric adenopathy are gastrointestinal and lymphoma. To the best of our knowledge, there are no reports of germ cell tumor (GCT) presenting with mesenteric adenopathy. Methods: Four patients with GCTs presenting with mesenteric adenopathies were treated in two academic centers (OHSU and USC) by a single surgeon since 2004. All pathologies were non-seminomatous GCT. Their presentation, clinico-pathologic findings and outcome are reviewed. Results: Two cases (19 and 51 yo) were IGCCC poor risk, stage II, testicular GCTs presenting with bulky retroperitoneal, periportal and mesenteric adenopathy. They both underwent post-chemo RPLND with mesenteric lymph node biopsy/resection. The intraoperative mesenteric lymph node frozen section study in one case revealed embryonal cell carcinoma and teratoma; he had early postoperative recurrence and is awaiting high dose chemotherapy and autologous stem cell transplant (HDC/ASCT). The other was teratoma and underwent resection, however he developed lung metastases with elevated AFP 6 months later and was treated with HDC/ASCT, being disease free for 2.5 years. The third case was a 29 yo IGCCC good risk testicular GCT who presented with retroperitoneal (II B) and mesenteric lymphadenopathy. He underwent post-chemo exploration and intraoperative frozen section of the mesenteric lymph nodes showed fibrosis and histiocytic infiltration; therefore classic RPLND was completed. The fourth case was a 24 yo HIV (-) patient with extragonadal GCT originating from the rectosigmoid. At presentation, he had a widespread mesenteric adenopathy, partially responded to primary (BEP) and salvage chemotherapy (VIP); he underwent recto/sigmoid resection, RPLND and PLND and had 52/104 lymph nodes positive for yolk sac tumor. He was referred for HDC/ASCT. Three cases were done recently with limited follow-up. Conclusions: The most common etiologies for mesenteric adenopathy are inflammatory, infection and neoplastic diseases. In the presence of germ cell tumor however, mesenteric adenopathy is most likely secondary to metastasis rather than secondary pathology.
Clinical Outcome after Adoptive Infusion of BPX-501 Cells (donor T cells transduced with iC9 suicide gene) in Children Given Alpha/Beta T-Cell Depleted HLA-Haploidentical Hematopoietic Stem Cell Transplantation (haplo-HSCT): Preliminary Results of a Phase I-II Trial
Authors: Franco Locatelli, Pietro Merli, Giuseppina Li Pira, Valentina Bertaina, Barbarella Lucarelli, Letizia Pomponia Brescia, Mauro Montanari, Daniela Pende, Michela Falco, Daria Pagliara, Maria Giuseppina Cefalo, Alessandro Moretta, Concetta Quintarelli, Brigitte Strahm, Waseem Qasim, Mary Slatter, Lorenzo Moretta, Annemarie Moseley, Alice Bertaina
Journal: Blood (2015)
Effect of cyclooxygenase inhibition on CXCR3 ligand secretion in breast cancer.
Authors: H. Bronger, S. Kraeft, A. Stöckel, A. Welk, M. Kiechle, M. Schmitt, U. R. M. Schwarz-Boeger
Journal: Journal of Clinical Oncology (2011)

45 Background: In murine cancer models, the two IFN-γ inducible chemokines CXCL9 and CXCL10, those bind to the common receptor CXCR3, recruit NK cells and tumor-suppressive lymphocytes into the tumor site and impair tumor growth and metastatic spread. In human breast cancer (BC), we and others have shown that high levels of CXCL9 mRNA correlate with favorable prognosis and the number of infiltrating lymphocytes. Raising the intratumoral level of CXCR3 ligands might therefore be a feasible way to enhance the infiltration by tumor-suppressive immune cells and to improve immune intervention in breast cancer. Inhibition of cyclooxygenases (COX) has been shown to inhibit tumor growth and metastases formation in a lymphocytic and IFN-γ dependent manner. We therefore tested whether COX inhibition induces CXCR3 ligand secretion from breast cancer cells. Methods: Human MCF-7 and MDA-MB 231 BC cells were stimulated with IFN-γ with or without prostaglandin E 2 (PGE 2 ) or COX inhibitors (indomethacin, aspirin, celecoxib). CXCL9 and CXCL10 release was measured by ELISA. COX-1 and COX-2 expression was measured in 45 BC samples and correlated with intratumoral CXCR3 ligand concentration. Results: Prostaglandin E 2 inhibits CXCL10 and CXCL9 release from breast cancer cells. Aspirin and indomethacin enhance the INF-γ mediated secretion of these CXCR3 ligands by inhibition of endogenous cyclooxygenases. Celecoxib has this effect only at low concentrations, at higher concentrations is shows PGE 2 agonistic effects. In human breast cancer samples, COX-2 overexpression inversely correlates with CXCR3 ligand concentration, which shows that the mechanism of PGE 2 induced CXCL9/CXCL10 suppression might also be relevant in vivo. Conclusions: Suppressing endogenous PGE 2 by cyclooxygenase inhibition increases CXCL9 and CXCL10 release from breast cancer cells and is therefore a feasible way to enhance the infiltration of breast tumors by tumor-suppressive lymphocytes. However, our results show that unselective COX inhibitors might be more suitable than the COX-2 specific celecoxib. Clinical trials are now warranted to clarify the mechanisms and therapeutic efficacy of COX inhibition in breast cancer.
Impact of Surveillance Stool Culture Guided Selection of Antibiotics in Allogeneic Hematopoietic Stem Cell Transplant Patients
Authors: Davinder Paul, Anant Ganesh Gokarn, Vasudev Bhat, Vivek Bhat, Avinash Bonda, Saurabh Zanwar, Libin Mathew, Sadhana Kannan, Deepa Susan, Tapan Saikia, Navin Khattry
Journal: Blood (2016)
Inhibition of Plasminogen Activator Inhibitor (PAI)-1 Corrects Diabetic CD34+ Dysfunction.
Authors: Sugata Hazra, Yagna P.R. Jarajapu, Li Liu, Sergio Caballero, Valerie Stepps, Ashay Bhatwadekar, Michael E. Boulton, Paul J. Higgins, Stephen H. Bartelmez, Maria B. Grant
Journal: Blood (2010)
Relationship of BTG2 expression and anastrozole resistance in breast cancer.
Authors: S. Nishiya, H. Jinno, T. Hayashida, M. Takahashi, Y. Kitagawa
Journal: Journal of Clinical Oncology (2011)

220 Background: The B-cell translocation gene-2 (BTG2) belongs to a class of proteins known as the Tob and BTG antiproliferative protein family. It was shown that estrogen and progesterone suppress BTG2 expression for the development of mammary gland. We demonstrated that proliferation rate of low level BTG2 expression in MCF7 was strongly inhibited by the administration of tamoxifen. In postmenopausal breast cancer patients, androgens can be converted to mitogenic estrogens by aromatase in breast cancer cells. Based on these results, we hypothesized that BTG2 expression affects the sensitivity against aromatase inhibitior. Methods: We used tetracycline-inducible BTG2 expression model in MCF7 stably transfected with the human aromatase gene (MCF7/tet/aro) as in vitro models of aromatase-driven breast cancer. The effects of BTG2 expression and administration of anastrozole in breast cancer cells were assessed by proliferation assays. Results: Administration of androstendion increased 79.1% of cellular proliferation, suggested that introduced aromatase gene worked well. Elevated level of BTG2 mRNA expression by tetracycline treatment was confirmed by Quantitative-RTPCR. Anastrozole treatment (100nM) reduced 37.8% of cellular proliferation ability, whereas the concomitant administration of tetracycline and anastorozole reduced 59.0% of cellular proliferation. These results suggested that the inhibitory effect of anastrozol for cellular proliferation was enhanced under the condition of BTG2 expression. Conclusions: Our results suggested loss of BTG2 expression may be affects the sensitivity against aromatase inhibitor.
Long Term Follow-up of 121 Elderly Patients with Philadelphia-Positive Acute Lymphoblastic Leukaemia (Ph+ALL) Treated in Prospective GMALL Trials Supports a Greater Emphasis On Allogeneic SCT as Definitive Postremission Therapy.
Authors: Heike Pfeifer, Christoph Wettner, Barbara Wassmann, Aristoteles A.N. Giagounidis, Matthias Stelljes, Ulrich Duehrsen, Marc Schmalzing, Markus Schaich, Maike De Wit, Arnold Ganser, Winfried Gassmann, Michael Pfreundschuh, Nicolai Haertel, Knut Wendelin, Mathias Schmid, Hans Joachim Beck, Jolanta Dengler, Heinz-August Horst, Michael Lübbert, Hubert Serve, Nicola Goekbuget, Dieter Hoelzer, Oliver G. Ottmann
Journal: Blood (2012)
Toward Individualized Therapy: Correlation of Mutation Analysis with in Vitro high Throughput Drug Sensitivity Testing in New Diagnosis and Relapsed Acute Myeloid Leukemia
Authors: Pamela S. Becker, Michael W. Schmitt, Zhiyi Xie, Andrew R Carson, Bradley Patay, Seyed Sina Khankhajeh, Qi Wei, Ling-Hong Hung, Timothy Martins, Elihu H. Estey, C. Anthony Blau, Vivian G. Oehler, Ka Yee Yeung
Journal: Blood (2015)
The impact of preoperative ASA score and serum albumin on early complication and survival rate of patients undergoing radical cystectomy for bladder cancer.
Authors: Hooman Djaladat, Adrian Stuart Fairey, Jie Cai, Gus Miranda, Eila C. Skinner, Siamak Daneshmand
Journal: Journal of Clinical Oncology (2012)

4576 Background: American Society of Anesthesiologist Score (ASA-S) is used to evaluate patient physical status before surgery. Serum albumin (Alb) is also a marker of nutritional status. We evaluated the impact of preoperative ASA-S and Alb on early complication rate and survival of patients who underwent radical cystectomy for bladder cancer. Methods: 1964 patients with primary bladder cancer underwent radical cystectomy between 1971 and 2008 at USC. Preoperative serum Alb and ASA-S were available in 1471 and 1140 patients respectively. Post cystectomy early complication was defined as any surgery related/unrelated event leading to lengthening hospital stay or re-admission within 90 days of surgery. Recurrence free survival (RFS) and overall survival (OS) for these cohorts were reviewed using a Kaplan-Meier and Cox proportional hazards models. Results: The demographic data of patients based on their serum Alb and ASA-S is presented in the Table. The median follow up was 12.4 years (0 - 36.6 yrs). Low serum Alb (&lt;3.4 g/dL) and high ASA-S (3 or 4) were associated with higher early complication rate (43% vs. 33%, p= 0.03 and 40% vs. 28%, p= 0.0001 respectively). In multivariable analysis, low serum Alb level was an independent predictor of RFS (HR 1.35, 95% CI 1.00-1.81) and OS (HR 1.62, 95% CI 1.29-2.04). High ASA-S was an independent predictor of OS (HR 1.45, 95% CI 1.13-1.85), but not RFS. Conclusions: Preoperative low serum Alb and high ASA-S are independently predictive of post cystectomy decreased OS. Low serum Alb is also a risk factor for recurrence after cystectomy. These parameters potentially could be used in nomograms to predict post-cystectomy prognosis. [Table: see text]
Distilling ethics, compassion, science and the art of medicine
Authors: Leong Ng, Yolande Lucire
Journal: BMJ (2016)

We agree with Wise.1 Clinicians, patients, their families, and regulators must all understand the difference between treatments that are potentially curative and the majority that are palliative. Based on risks, benefits, and possibilities, the patient gives informed consent for an intervention.

In Sydney, Australia, oncologists in a reputable hospital have arranged to have a senior colleague charged with “underdosing,” creating the impression …
A Phase 1 Trial of Inotuzumab in Combination with CVP (Cyclophosphamide, Vincristine, Prednisone) for Relapsed/ Refractory CD22+ Acute Leukemia (SWOG 1312)
Authors: Anjali S. Advani, Anna Moseley, Michaela Liedtke, Margaret O'Donnell, Megan Othus, Martha P. Mims, Kristen O'Dwyer, Harry P. Erba
Journal: Blood (2016)
Dickkopf-1 promotes hematopoietic regeneration via direct and niche-mediated mechanisms
Authors: Heather A Himburg, Phuong L Doan, Mamle Quarmyne, Xiao Yan, Joshua Sasine, Liman Zhao, Grace V Hancock, Jenny Kan, Katherine A Pohl, Evelyn Tran, Nelson J Chao, Jeffrey R Harris, John P Chute
Journal: Nature Medicine (2016)
Abstract 12717: Improvement of Longitudinal Function is Closely Related to Reverse Remodeling in Cardiac Resynchronization Therapy
Authors: Nina E Hasselberg, Kristina H Haugaa, Anne Bernard-Brunet, Erik Kongsgård, Erwan Donal, Thor Edvardsen
Journal: Circulation (2014)

Introduction: Response to cardiac resynchronization therapy (CRT) is often defined as reverse remodeling as a reduction in left ventricular (LV) end systolic volume (ESV). How myocardial mechanics are affected by biventricular pacing is not fully clarified. We tested the hypothesis that longitudinal and circumferential function are affected differently by biventricular pacing. Methods: Echocardiography (two dimensional) was performed before and 6 months after CRT implantation in heart failure patients with LV ejection fraction (EF) ≤ 35% and QRS ≥ 120 ms. LV function was assessed by EF and by global longitudinal (GLS) and global circumferential (GCS) strain from 16 LV segments by speckle tracking technique. CRT responders were defined as patients with reverse remodeling with a reduction in ESV ≥ 15% at 6 months. Results: We included 138 heart failure patients (65±10 years, 22% women, NYHA functional class 2.8±0.4, 48% ischemic cardiomyopathy). In the total population, GLS did not change (-8.5±3.9% to -8.9±4.7%, p=0.31) after 6 months with biventricular pacing, while GCS (-11.3±3.3% to -14.2±4.5%, p&lt;0.001) and EF (27±9% to 36±12%, p&lt;0.001) improved. Analyzing CRT responders (62%) and non-responders separately, GLS improved in responders (-8.4±3.8% to -9.5±3.8%, p=0.02) but not in non-responders (-8.7±4.1% to -7.9±4.5%, p=0.30) (Figure). GCS improved in both groups (-11.3±3.0% to -15.0±4.3%, p&lt;0.001 and -11.4±3.8% to 13.0±4.7%, p=0.01). ΔGLS was a predictor of CRT response (OR 0.84 (0.75-0.95), p=0.009) and of ΔESV (1.62 (0.45-2.79), p=0.007) independently of ΔGCS. Conclusions: Biventricular pacing by CRT generally induced less changes in GLS than in GCS and EF. Importantly, GLS improved only in CRT responders with reverse remodeling. We suggest that reverse remodeling is more dependent on improved longitudinal function than circumferential function.
Outcome of adjuvant imatinib in patients with gastrointestinal stromal tumor: Results of a population-based, matched cohort study.
Authors: H. T. Hatoum, J. C. Trent, A. Guo, S. Lin, L. A. Sirulnik, M. Sasane
Journal: Journal of Clinical Oncology (2011)

10052 Background: There is limited data on adjuvant imatinib (IM) use in Gastrointestinal Stromal Tumor (GIST) patients (pts) outside of clinical trials. Using PharMetrics claims database (2000-2010), we compared outcomes (occurrence and time to 2nd surgery and follow up duration (FUP) of IM pts to those who did not receive IM (non-IM). Methods: De-identified information of pts undergoing surgery for primary GIST was extracted using GIST related ICD-9 and CPT codes. IM pts were defined as those receiving imatinib within 84 days post-surgery. IM pts were matched on age, gender, ICD-9s, and 1st surgery date with up to 8 non-IM pts. Pts receiving chemo/radiation, < 18 yrs, or with prior cancer history were excluded. Pts were followed from the 1st GIST surgery claim to end of data availability. IM and non-IM matched controls were compared on time to 2nd surgery, loss to FUP (i.e., no more claims for >3 months from last claim to study end), and a composite outcome of both using bivariate analyses and Cox regression controlling for age, Charlson comorbidity index, and diagnosis year. Results: From 192,482 pts with possible GIST ICD-9s, 6958 (5%) had GIST related surgery. Application of exclusion criteria resulted in identification of 118 IM and 4088 non-IM pts; with mean age of 64 (+/-15) yrs. There were more men (52%), 37% had initial surgery for tumor occurring in stomach, and median duration of IM therapy was 270 days. The median FUP post initial surgery in IM and non-IM pts was 499 and 318 days, respectively. The median time to 2nd surgery was 489 days in IM and 290 days in non-IM pts. About 2% of IM and 5% of non-IM pts had 2nd surgery; the difference was not statistically significant (P =0.18) due to low event rates. IM pts had significantly longer median FUP from initial surgery to composite outcome (433 vs. 320 days, p =0.002) than non-IM pts. Regression analysis showed that IM pts were less likely to have the composite outcome (2nd surgery or loss to FUP) compared to non-IM pts (HR= 0.501, P=0.0005). Conclusions: Patients receiving adjuvant IM were less likely to have 2nd surgery and the interval to 2nd surgery was prolonged. Additional analyses are needed to understand the impact of treatment duration on outcomes.
Physician Work Environment and Well-being
Authors: Lara Goitein, Patrick G. O’Malley, Rita F. Redberg
Journal: JAMA Internal Medicine (2016)

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Prevalence and Clinical Impact of Additional Cytogenetic Abnormalities in Patients (Pts) with Myelodysplastic Syndromes (MDS) and Deletion 5q from the MDS-003 and MDS-004 Studies
Authors: Aristoteles Giagounidis, Alan F. List, Eva Hellstrom-Lindberg, Ghulam J. Mufti, Brigitte Schlegelberger, John Morrill, Chengqing Wu, Barry Skikne, Pierre Fenaux, Gudrun Göhring
Journal: Blood (2014)
Compulsory drug detention centres: time to question their continued use?
Authors: Anne Bergenstrom, Gino Vumbaca
Journal: The Lancet Global Health (2016)

In the Lancet Global Health, Martin Wegman and colleagues present their study of opioid use in opioid-dependent individuals released from compulsory drug detention centres (CDDCs) compared with those from voluntary methadone treatment centres (VTCs) in Malaysia.1 This study was the first prospective observational study to compare drug-use outcomes between the two facility types. The investigators showed that opioid-dependent individuals in CDDCs were significantly more likely to relapse to opioid use after release than opioid-dependent individuals receiving methadone in VTCs (in unadjusted analyses, CDDC participants had significantly more rapid relapse to opioid use post-release compared with VTC participants [median time to relapse 31 days {IQR 26–32} vs 352 days {256–inestimable}, log rank test p<0·0001).
3rd ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3)
Authors: F. Cardoso, A. Costa, E. Senkus, M. Aapro, F. André, C.H. Barrios, J. Bergh, G. Bhattacharyya, L. Biganzoli, M.J. Cardoso, L. Carey, D. Corneliussen-James, G. Curigliano, V. Dieras, N. El Saghir, A. Eniu, L. Fallowfield, D. Fenech, P. Francis, K. Gelmon, A. Gennari, N. Harbeck, C. Hudis, B. Kaufman, I. Krop, M. Mayer, H. Meijer, S. Mertz, S. Ohno, O. Pagani, E. Papadopoulos, F. Peccatori, F. Penault-Llorca, M.J. Piccart, J.Y. Pierga, H. Rugo, L. Shockney, G. Sledge, S. Swain, C. Thomssen, A. Tutt, D. Vorobiof, B. Xu, L. Norton, E. Winer
Journal: Annals of Oncology (2016)

Advanced Breast Cancer (ABC) comprises both locally advanced (LABC) and metastatic breast cancer (MBC) [1]. Although treatable, MBC remains an incurable disease with a median overall survival of ∼2–3 years and a 5-year survival of only ∼25% [2–4]. Some more recent series seem to indicate an improvement in median overall survival [5, 6].
Prevention of Heart Failure
Authors: Tamara B. Horwich, Gregg C. Fonarow
Journal: JAMA Cardiology (2016)

In light of the increasing prevalence, morbidity, and mortality of heart failure, preventative strategies are urgently needed. Risk factors include coronary artery disease, renal insufficiency, diabetes, and smoking. Essential strategies for prevention of heart failure are modification of risk factors for its development, and detection and treatment of asymptomatic left ventricular dysfunction (ALVD). In patients with ALVD, angiotensin-converting enzyme (ACE) inhibitor and beta-blocker therapy can prevent progression to symptomatic heart failure. Additional recently identified preventative strategies include ACE inhibitor therapy for all coronary artery disease and diabetic patients, clopidogrel therapy in acute coronary syndromes, and avoidance of calcium channel blockers and alpha-blockers as first-line antihypertensive therapy.
Response of the human kidney to clamp ischemia.
Authors: Barbara Ercole, Kathleen Torkko, William Hilton, Manjery A. Venkatachalam, Joel M. Weinberg, Dipen J. Parekh
Journal: Journal of Clinical Oncology (2012)

365 Background: Structural changes in tubule cells during clamp ischemia are well characterized for animal models, but their timing and extent in the human kidney has not been established and may differ significantly. To better define the human response, we biopsied uninvolved areas of kidney in patients undergoing open partial nephrectomy for renal masses. Methods: Biopsies of 40 patients undergoing PN were obtained at specified time intervals: before renal artery clamping, then during periods ranging from 15 to 60 min. of warm and cold ischemia (80% &gt; 30 min.), and then after 5 minutes of reflow. These biopsies were assessed for ultrastructure (N=39) and for immunofluorescence and rhodamine phalloidin staining (N=22). Results: During the clamp period, apical membrane structure was remarkably well preserved with only patchy brush border clubbing, fragmentation, desquamation and blebbing and not in all patients. Mitochondria developed progressive swelling, which paradoxically was more prominent in distal than proximal tubule cells. This resolved during the 5 minutes of reflow in most cells in most patients, but persistence of swelling and development of matrix condensation occurred occasionally. Using a composite 0-5 scale covering the full spectrum of ultrastructural changes, average scores were: Preclamp 1.02±0.07, End clamp 2.18±0.07, Post clamp 1.86±0.09. Consistent with the ultrastructure, staining for F-actin with rhodamine phalloidin was well preserved. Immunsotaining for phosphotyrosine, which reflects cellular ATP content was decreased in 68.4% of the clamp biopsises and 52.6% of the postclamp biopsies with larger changes in proximal tubules, however B1 integrin was decreased in only one post clamp biopsy. ICAM-1 expression in peritubular capillaries was increased in 46.7% of the clamp biopsies and 66.7% of post clamp biopsies. None of the patients developed acute kidney injury. Conclusions: These data provide the first detailed analysis of the structural response of the human kidney to clamp ischemia and document many of the expected structural alterations based on prior animal work, but indicate a greater than expected resistance to injury in this commonly used clinical application of clamp ischemia.
The Prevalence of Pantoprozole Associated Thrombocytopenia in a Community Hospital - A Retrospective Study.
Authors: Randi Katz, Jason Bratcher, Efrat Dotan, Carrie Wasserman, Michelene Liebman, Sivakumar Reddy, Amy Michael, Aliasad Arastu, Georgia Panagopoulos, Colette Spaccavento
Journal: Blood (2005)