tbuckley/cabot-search huggingface dataset:
Bisphosphonate-associated osteonecrosis of the jaw in patients with metastatic cancer
Authors: L. D. Powell, J. Nguyen, M. Singh, K. Kay
Journal: Journal of Clinical Oncology (2008)

20591 Background: Given reports of osteonecrosis of the jaw (ONJ) and bisphosphonate therapy (BPT), we conducted a 7-year review of patients receiving BPT in our clinic for clinical and radiographic evidence of ONJ. Our clinic population is a predominantly indigent population with poor access to dental care and, consequently, significant pre-existing dental disease. Methods: Pharmacy records and medical charts were reviewed from 9/99 to 11/06, identifying 255 patients given BPT; 14% received pamidronate exclusively and the rest zoledronic acid. The indication was multiple myeloma (14%), breast cancer (43%), and other solid tumors (43%). As the risk of ONJ increases with increasing duration of therapy, charts of 66 patients who received ≥ 10 cycles of therapy were analyzed further for clinical signs (jaw or facial pain), radiographic signs (plain films, CT/scans, or bone scans), and physical findings consistent with ONJ (dental abscesses and/or exposed bone). Radiology records were available for 66/66 and clinical charts for 50/66 of cases. An observational study of all other patients active in our clinic over the past 4 years (>2,000 pts.) for ONJ was also reviewed. Results: By our initial screening criteria, ONJ was suspected in 17/66 patients: 3/17 by radiographic criteria alone; 8/17 by clinical criteria alone (facial or jaw pain which resolved without intervention; no radiographic studies done); 2/17 with clinical and radiographic studies suggestive of ONJ but not confirmed on dental examination; 4/17 with clinical and radiographic evidence of ONJ which was confirmed by dental examination. Thus, 4/66 (6%) patients developed ONJ while on extended BPT. The initial clinical or radiographic findings in the other 13 patients were similar to those who ultimately developed ONJ. No cases of confirmed ONJ were identified in 189 patients receiving less than 10 cycles of BPT or in those not receiving any BPT. Conclusions: Our retrospective study confirms the incidence of ONJ in patients receiving long-term BPT published by other research groups. Our experience further highlights the difficulty of identifying these patients based on clinical or radiographic findings. Treatment guidelines limiting the duration of BPT would likely reduce the incidence of ONJ. No significant financial relationships to disclose.
Quality Controls Of Immune Regulatory Properties Of Ex-Vivo, GMP-Grade Expanded Mesenchymal Stromal Cells For Clinical Use
Authors: Cedric Menard, Luciano Pacelli, Giulio Bassi, Joelle Dulong, Isabelle Bezier, Jasmina Zanoncello, Francesco Bifari, Mario Ricciardi, Hubert Schrezenmeier, Luc Sensebé, Karin Tarte, Mauro Krampera
Journal: Blood (2013)
Thrombocytopenia in patients with melanoma receiving immune checkpoint inhibitor therapy
Authors: Eileen Shiuan, Kathryn E. Beckermann, Alpaslan Ozgun, Ciara Kelly, Meredith McKean, Jennifer McQuade, Mary Ann Thompson, Igor Puzanov, John P. Greer, Suthee Rapisuwon, Michael Postow, Michael A. Davies, Zeynep Eroglu, Douglas Johnson
Journal: Journal for ImmunoTherapy of Cancer (2017)

<h3>Background</h3> Immune checkpoint inhibitors, including antibodies against programmed death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4), are being used with increasing frequency for the treatment of cancer. Immune-related adverse events (irAEs) including colitis, dermatitis, and pneumonitis are well described, but less frequent events are now emerging with larger numbers of patients treated. Herein we describe the incidence and spectrum of thrombocytopenia following immune checkpoint inhibitor therapy and two severe cases of idiopathic thrombocytopenic purpura (ITP). <h3>Case presentations</h3> A 47-year-old female with recurrent BRAF mutant positive melanoma received combination anti-PD-1 and anti-CTLA-4. Two weeks later, she presented with mucosal bleeding, petechiae, and thrombocytopenia and was treated with standard therapy for ITP with steroids and intravenous immunoglobulin (IVIG). Her diagnosis was confirmed with bone marrow biopsy, and given the lack of treatment response, she was treated with rituximab. She began to have recovery and stabilization of her platelet count that ultimately allowed her to be retreated with PD-1 inhibition with no further thrombocytopenia. A second patient, a 45-year-old female with a BRAF wild-type melanoma, received anti-PD-1 monotherapy and became thrombocytopenic 43&nbsp;days later. Three weeks of steroid treatment improved her platelet count, but thrombocytopenia recurred and required additional steroids. She later received anti-CTLA-4 monotherapy and developed severe ITP with intracranial hemorrhage. Her ITP resolved after treatment of prednisone, IVIG, and rituximab and discontinuation of checkpoint inhibition. In a retrospective chart review of 2360 patients with melanoma treated with checkpoint inhibitor therapy, &lt;1% experienced thrombocytopenia following immune checkpoint inhibition, and of these, most had spontaneous resolution and did not require treatment. <h3>Conclusions</h3> Thrombocytopenia, especially ITP, induced by immune checkpoint inhibitors appears to be an uncommon irAE that is manageable with observation in mild cases and/or standard ITP treatment algorithms. In our series, the majority of patients had mild thrombocytopenia that resolved spontaneously or responded to standard corticosteroid regimens. However, in two severe cases, IVIG and rituximab, in addition to steroids, were required. Checkpoint inhibition was resumed successfully in the first patient but rechallenge was not tolerated by the second patient.
Development of a Strain of Spontaneously Hypertensive Rats
Authors: Kozo Okamoto, Kyuzo Aoki
Journal: Circulation (1963)

A male rat with  high systolic blood pressures of 150 to 175 mmHg persisting for more than one month and a female rat with blood pressures slighty above the average, 130 to 140 mmHg, were selected from among 68 Wistar strain rats in normal condition and mated to obtain F1 rats. Of these F1 rats, males and females with hypertension (blood pressure exceeding 150 mmHg) persisting for more than a month (mostly over 2 months) were mated to produce F2 rats. The procedure was repeated to obtain F3, F4, F5 and F6 rats totaliag 380 animals. The weights and blood pressures (by the tail-water-plethysmographic method) were measured once weekly biginning at 4 weeks of age, and the results can be summarized as follows : 1. In body weight, the F rats showed little difference from the normal controls. 2. The blood pressures of F rats rose with age and from generation to generation, increasing significantly above those of normotensive controls of the same age after 20 weeks of age among female F1, after 15 weeks among male F1 and also male and female F2, and after 10 weeks among all F3 to F6 rats. E. g., the average systolic blood pressure of F5 at 25 weeks of age was 206+__-18.5 mmHg in the male and 193+__-20.5 mmHg in female rats. The blood pressures of normotensive controls remained at 131 to 136 mmHg in the male and 130 to 135 mmHg in female rats after 10 weeks of age. 3. Many F rats showed spontaneous hypertension. The incidence of the spontaneous occurrence of hypertension increased, and the development of hypertension occurred at younger ages from generation to generation. All of the F3 to F6, rats developed spontaneous hypertension within 15 weeks of age. Severe hypertension with blood pressures exceeding 200 mmHg began to observed among F2. The incidence of such severe hypertension increased with each generation, so that among male animals it inceased from only 9% in F2 to 35% in F3, 42% in F4, and 56% in F5, and in female animals from 3% in F2, 16% in F3, 33% in F4, and 37% in F5. The authors have named this Wistar strain of rats with spontaneous occurrence of hypertension as spontaneously hypertensive rats (Okamoto-Aoki). 4. The blood pressures of β-line rats from parents with very high blood pressures were significantly higher than among α-line rats from parents with moderately high blood pressures at the same age. 5. There was no difference in the blood pressures of offsprings resulting from inbreeding and those from cross breeding. The male blood pressure averaged about 10.6 mmHg above the female value in spontaneous hypertension, and hypertension developed at lower ages in the male. 6. It is a question for future study whether the spontaneous hypertension induced in rats in this Study is comparable in characteristics with essential hypertension in man.
Serum Concentrations of DKK-1 Correlate with the Extent of Bone Disease in Multiple Myeloma.
Authors: Martin Kaiser, Maren Mieth, Peter Liebisch, Susanne Rötzer, Christian Jakob, Claudia Fleissner, Edgar Braendle, David Stover, Malte Peters, Orhan Sezer, Ulrike Heider
Journal: Blood (2007)
What can China learn from the US Affordable Care Act?
Authors: Changjing Cai, Hong Shen, Shan Zeng
Journal: BMJ (2017)

McCarthy reports on President Barack Obama’s contribution to the Affordable Care Act (ACA).12 The ACA has attracted the attention of Chinese doctors, bringing into sharp relief the current difficulties with medical care in China and providing possible solutions. 

An important provision of the ACA allows young adults to stay on their parents’ insurance …
MicroRNA-33 protects against neointimal hyperplasia induced by arterial mechanical stretch in the grafted vein
Authors: Kai Huang, Han Bao, Zhi-Qiang Yan, Lu Wang, Ping Zhang, Qing-Ping Yao, Qian Shi, Xiao-Hu Chen, Kai-Xuan Wang, Bao-Rong Shen, Ying-Xin Qi, Zong-Lai Jiang
Journal: Cardiovascular Research (2017)

Mechanical factors play significant roles in neointimal hyperplasia after vein grafting, but the mechanisms are not fully understood. Here, we investigated the roles of microRNA-33 (miR-33) in neointimal hyperplasia induced by arterial mechanical stretch after vein grafting.Grafted veins were generated by the 'cuff' technique. Neointimal hyperplasia and cell proliferation was significantly increased, and miR-33 expression was decreased after 1-, 2-, and 4-week grafts. In contrast, the expression of bone morphogenetic protein 3 (BMP3), which is a putative target of miR-33, and the phosphorylation of smad2 and smad5, which are potential downstream targets of BMP3, were increased in the grafted veins. miR-33 mimics/inhibitor and dual luciferase reporter assay confirmed the interaction of miR-33 and BMP3. miR-33 mimics attenuated, while miR-33 inhibitor accelerated, proliferation of venous smooth muscle cells (SMCs). Moreover, recombinant BMP3 increased SMC proliferation and P-smad2 and P-smad5 levels, whereas BMP3-directed siRNAs had the opposite effect. Then, venous SMCs were exposed to a 10%-1.25 Hz cyclic stretch (arterial stretch) by using the FX4000 cyclic stretch loading system in vitro to mimic arterial mechanical conditions. The arterial stretch increased venous SMC proliferation and repressed miR-33 expression, but enhanced BMP3 expression and smad2 and smad5 phosphorylation. Furthermore, perivascular multi-point injection in vivo demonstrated that agomiR-33 not only attenuates BMP3 expression and smad2 and smad5 phosphorylation, but also slows neointimal formation and cell proliferation in grafted veins. These effects of agomiR-33 on grafted veins could be reversed by local injection of BMP3 lentivirus.The miR-33-BMP3-smad signalling pathway protects against venous SMC proliferation in response to the arterial stretch. miR-33 is a target that attenuates neointimal hyperplasia in grafted vessels and may have potential clinical applications.
CXCR4 Blockade as a New Targeted Therapy for Acute Myeloide Leukemia Characterised by High Cell Surface Density of CXCR4.
Authors: Yanyan Zhang, Dima Jouni, Monika Wittner, Hakim Bouamar, Herve Dombret, Paul Coppo, Paule Opolon, Nobutaka Fujii, Mamoru Ito, William Vainchenker, Stephane de Botton, Fawzia Louache
Journal: Blood (2009)
Characterization of Hematopoietic and Non-Hematopoietic Stem/Progenitor Cells in Freshly Isolated Adult Human Bone Marrow Using an 8-Color Flow Cytometric Assay.
Authors: Ferda Tekinturhan, Ludovic Zimmerlin, Vera S. Donnenberg, Melanie E. Pfeifer, Darlene A. Monlish, Birol Guvenc, James Bradley, Albert D. Donnenberg
Journal: Blood (2007)
Extended lymphadenectomy and adjuvant chemotherapy in muscle-invasive bladder cancer treated by radical cystectomy.
Authors: Peter J. Bostrom, Tuomas Mirtti, Martti Nurmi, Matti Laato, Bas W.G. Van Rhijn, Neil Eric Fleshner, Antonio Finelli, Michael A. S. Jewett, Malcolm J. Moore, Srikala S. Sridhar, Ian Tannock, Alexandre Zlotta
Journal: Journal of Clinical Oncology (2012)

287 Background: Level 1 evidence is weak for adjuvant chemotherapy (AC) after cystectomy, but surveys indicate physicians refer patients for AC more frequently than for neoadjuvant chemotherapy (NC). The exact benefit of an extended pelvic lymph node dissection (ePLND) remains debated. We addressed the issue of AC and ePLND analyzing two academic centers RC databases with opposite approaches, one using ePLND and AC, the other performing a limited lymph node dissection and no AC. Methods: Two ethics approved RC databases including consecutive BC patients undergoing RC at the University Health Network, Canada and the University of Turku, Finland were studied. Excluding non-urothelial cases and patients receiving NC, 563 patients were available for analysis. Clinicopathological variables, rate and extent of PLND and rate of adjuvant cisplatin-based chemotherapy were analyzed using the χ 2 -test. Kaplan-Meier method and multivariate Cox regression analysis were used to analyze survival. Results: In Toronto, patients had more extensive PLNDs (&gt;10 nodes removed, 58% vs. 8%, p&lt;0.001), higher rate of nodal metastases (26% vs. 7%, p&lt;0.001), and received more often AC (21% vs. 1%, p&lt;0.001). Positive margin rates were similar (4% in both centers). No BC specific survival difference was demonstrated in ≤ pT2a or in pT4a tumors. There was a trend for improved survival in pT2b tumors (10y BC specific survival 65% vs. 42%, p=0.23) and a significant difference favouring the Toronto cohort in pT3a and pT3b tumors (55% vs. 31%, p=0.025; 43% vs. 28% p=0.06, respectively). In multivariate analysis, N-stage (HR 2.5, 95% CI 1.5-4.1; p&lt;0001) and ePLND (HR 0.53, 95% CI 0.31-0.93, p=0.026) significantly affected disease specific survival. The benefit of AC did not reach significance (HR 0.61, 95% CI 0.36-1.05, p=0.072). An interaction model combining ePLND and AC was significantly related to improved outcome (HR 0.49, 95% CI 0.26-0.92, p=0.026). Conclusions: Despite not being randomized, using 2 study cohorts that received completely opposite managements in terms of ePLND and AC, our results support that ePLND and AC may offer a survival advantage in T2b and especially in T3 BC treated with RC.
A Large Scale Evaluation of Genetic Variation in Immune and Inflammation Genes and Risk of Non-Hodgkin Lymphoma.
Authors: James R. Cerhan, Stephen M. Ansell, Zachary S. Fredericksen, Neil E. Kay, Mark Liebow, Timothy G. Call, Ahmet Dogan, Julie M. Cunningham, Wen Liu, William R. Macon, Thomas E. Witzig, Thomas M. Habermann, Susan L. Slager
Journal: Blood (2006)
Determining the clinical significance of the improvement in health-related quality of life (HRQoL) measures in oncology patients
Authors: J. Cassinello, J. Carulla, V. Valentín, C. A. Rodríguez, P. Gascón, J. García-Mata, R. Colomer, E. Baró, J. A. Gasquet
Journal: Journal of Clinical Oncology (2008)

20622 Background: Cancer-related fatigue is gaining importance as an outcome measure. Perform Questionnaire (PQ) is a recently developed and validated scale for the assessment of perceptions about chronic renal failure (CRF). The minimally important difference (MID) that implies a clinically meaningful outcome has been determined to enable better interpretation of the observed numerical differences in PQ. Methods: In an observational, longitudinal, multicentre study in cancer patients with CRF, data (demographics, haemoglobin (Hb) levels, and HRQoL measures (PQ and FACT-F) were collected at inclusion and 3 months later. An Hb increase of 1g/dL was considered as the minimally important clinical change by which to evaluate HRQoL results. ‘Improved’ patients were those who experienced an increase in Hb≥1g/dL. ‘Stable’ patients had a change in Hb<1g/dL to a lower limit of -1g/dL. The difference in the mean HRQoL change score between the two groups was the MID of the measurement; MID was determined for PQ and FACT-F. Results: In total, 288 patients were included; 34.6% had breast cancer, 12% colon cancer, 12% lung cancer; 28.4% had anaemia (Hb<11g/dL). At 3 months, 87 patients (30.2%) improved while 201 (69.8%) remained stable; the difference in mean change in Hb level between stable and improved patients was 2.09g/dL. Pearson’s correlation between Hb level and PQ score at baseline was 0.24. Conclusions: MID can be useful to help interpret HRQoL score changes. An improvement of approximately 4 and 3 in PQ and FACT-F, respectively, can be considered as MIDs when an Hb≥1g/dL is seen as the minimally important clinical change. # items Theoretical range in questionnaire score Mean change (SD) of score in stable patients (N=87) Mean change (SD) of score in improved patients (N=201) MID PQ 12 12 (worse) - 60 (better) 0.03 (12.69) 3.72 (10.22) 3.69 FACT-F 13 13 (better) - 65 (worse) -0.87 (11.14) -3.64 (9.66) 2.77 No significant financial relationships to disclose.
Treatment with Amifostine, Topotecan and Cytarabine in 31 Consecutive Patients with High Risk Myelodysplastic Syndrome: A Phase II Trial.
Authors: Kamal Bouabdallah, Frederic Bauduer, Michel Renoux, Arnaud Pigneux, Reza Tabrizzi, Fontanet Bijou, Thibaut Legay, Gerald Marit, Josy Reiffers, Jean M. Boiron
Journal: Blood (2004)
Synovial features of patients with rheumatoid arthritis and psoriatic arthritis in clinical and ultrasound remission differ under anti-TNF therapy: a clue to interpret different chances of relapse after clinical remission?
Authors: Stefano Alivernini, Barbara Tolusso, Luca Petricca, Laura Bui, Gabriele Di Sante, Giusy Peluso, Roberta Benvenuto, Anna Laura Fedele, Franco Federico, Gianfranco Ferraccioli, Elisa Gremese
Journal: Annals of the Rheumatic Diseases (2017)

To define the synovial characteristics of patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in clinical and ultrasound remission achieved by combination therapy with methotrexate (MTX) and tumour necrosis factor (TNF) blockers.Patients with RA in remission (n=25) (disease activity score (DAS)<1.6 for at least 6 months), patients with RA in low disease activity (LDA) (n=10) (1.6<DAS<2.4 for at least 6 months) and patients with PsA in remission (n=18) (DAS<1.6 and Psoriasis Area Severity Index (PASI)=0 for at least 6 months) achieved by MTX+anti-TNF (adalimumab 40 mg or etanercept 50 mg) with power Doppler (PDUS)-negative synovial hypertrophy underwent synovial tissue biopsy. Patients with RA with high/moderate disease naïve to treatment (n=50) were included as a comparison group. Immunostaining for cluster designation (CD)68, CD21, CD20, CD3, CD31 and collagen was performed.PDUS-negative patients with RA in remission showed lower histological scores for synovial CD68+, CD20+, CD3+ cells and CD31+ vessels and collagen deposition (p<0.05 for both lining and sublining) compared with PDUS-positive patients with RA with high/moderate disease. In addition, there was no significant difference in terms of lining and sublining CD68+, CD20+, CD3+, CD31+ cells and collagen comparing PDUS-negative patients with RA in remission and in LDA, respectively. On the contrary, PDUS-negative patients with PsA in remission showed higher histological scores for sublining CD68+ (p=0.02) and CD3+ cells (p=0.04) as well as CD31+ vessels (p<0.001) than PDUS-negative patients with RA in remission.PDUS-negative patients with RA in remission have comparable synovial histological features than PDUS-negative patients with RA in LDA. However, patients with PsA in remission are characterised by a higher degree of residual synovial inflammation than patients with RA in remission, despite PDUS negativity under TNF inhibition.
The role of sphingosine 1‐phosphate receptor 2 in bile‐acid–induced cholangiocyte proliferation and cholestasis‐induced liver injury in mice
Authors: Yongqing Wang, Hiroaki Aoki, Jing Yang, Kesong Peng, Runping Liu, Xiaojiaoyang Li, Xiaoyan Qiang, Lixin Sun, Emily C. Gurley, Guanhua Lai, Luyong Zhang, Guang Liang, Masayuki Nagahashi, Kazuaki Takabe, William M. Pandak, Phillip B. Hylemon, Huiping Zhou
Journal: Hepatology (2017)

Bile duct obstruction is a potent stimulus for cholangiocyte proliferation, especially for large cholangiocytes. Our previous studies reported that conjugated bile acids (CBAs) activate the protein kinase B (AKT) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling pathways through sphingosine 1-phosphate receptor (S1PR) 2 in hepatocytes and cholangiocarcinoma cells. It also has been reported that taurocholate (TCA) promotes large cholangiocyte proliferation and protects cholangiocytes from bile duct ligation (BDL)-induced apoptosis. However, the role of S1PR2 in bile-acid-mediated cholangiocyte proliferation and cholestatic liver injury has not been elucidated. Here, we report that S1PR2 is the predominant S1PR expressed in cholangiocytes. Both TCA- and sphingosine-1-phosphate (S1P)-induced activation of ERK1/2 and AKT were inhibited by JTE-013, a specific antagonist of S1PR2, in cholangiocytes. In addition, TCA- and S1P-induced cell proliferation and migration were inhibited by JTE-013 and a specific short hairpin RNA of S1PR2, as well as chemical inhibitors of ERK1/2 and AKT in mouse cholangiocytes. In BDL mice, expression of S1PR2 was up-regulated in whole liver and cholangiocytes. S1PR2 deficiency significantly reduced BDL-induced cholangiocyte proliferation and cholestatic injury, as indicated by significant reductions in inflammation and liver fibrosis in S1PR2 knockout mice. Treatment of BDL mice with JTE-013 significantly reduced total bile acid levels in serum and cholestatic liver injury.This study suggests that CBA-induced activation of S1PR2-mediated signaling pathways plays a critical role in obstructive cholestasis and may represent a novel therapeutic target for cholestatic liver diseases. (Hepatology 2017;65:2005-2018).
Validation of the Lung Function Score as a Valuable Parameter for the Assessment of Chronic Graft-Versus-Host Disease and Clinical Outcome After Allogeneic Haematopoietic Cell Transplantation.
Authors: Diana Ditz, Robert Rabanus, Christian Schulz, Daniel Wolff, Reinhard Andreesen, Ernst Holler, Gerhard Hildebrandt
Journal: Blood (2009)
Decreased Serum Levels of Surfactant Protein D (SP-D) Prior Transplant Is Associated with the Development of Bronchiolitis Obliterans (BO) and Idiopathic Pneumonia Syndrome (IPS) Following Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Takahiko Nakane, Hirohisa Nakamae, Hiroshi Kamoi, Hideo Koh, Yasunobu Takeoka, Erina Sakamoto, Hiroshi Kanashima, Hiroyoshi Ichihara, Mika Nakamae, Ki-Ryang Koh, Takahisa Yamane, Masayuki Hino
Journal: Blood (2006)