tbuckley/cabot-search huggingface dataset:
Durable clinical responses in patients with metastatic melanoma vaccinated with dendritic cells loaded with killed allogeneic melanoma cells
Authors: J. W. Fay, H. Ueno, J. Connolly, J. Banchereau, K. Palucka
Journal: Journal of Clinical Oncology (2006)

2576 Background: We demonstrated that DCs loaded with killed allogeneic tumors can cross-prime tumor-specific naïve CD8+T cells in vitro. Clinically this approach would overcome HLA restriction inherent to peptide vaccines and allow diversification of immune responses including priming of many clones of CD8 + and CD4 + T cells. Methods: Twenty (20) patients with metastatic melanoma were vaccinated with autologous monocyte-derived DCs loaded with killed allogeneic Colo829 melanoma cell line. A total of 8 vaccines were administered at monthly intervals. DCs were generated from monocytes by culturing with GM-CSF and IL-4 and activated by additional culture with TNFα and CD40 ligand. KLH was used as a control antigen. The first patient was accrued December, 2002 and the last November, 2003. Results: DC vaccinations induced durable objective clinical responses in two patients who had progressive metastatic disease after previous cytotoxic chemotherapy. One patient experienced a CR and one patient a PR both remissions have lasted ≥ 20 months. Fourteen patients were alive at 12 months and 9 patients are alive at the end of 2005. The estimated median overall survival is 22 months with a range of 2–31 months. DC vaccination led to elicitation of CD8 + T cell immunity specific to MART-1 tissue differentiation antigen, suggesting that cross-priming/presentation of melanoma antigens by the DC vaccines had occurred in vivo. Vaccinations were safe and tolerable. There were no significant adverse events. Conclusions: The present results justify the design of larger follow-up studies to assess the immunological and clinical response to DC vaccines in patients with metastatic melanoma and other malignant diseases. No significant financial relationships to disclose.
The multiple roles of chemokines in the mechanisms of stent biocompatibility
Authors: Dhanya Ravindran, Keyvan Karimi Galougahi, Joanne T M Tan, Mary M Kavurma, Christina A Bursill
Journal: Cardiovascular Research (2020)

While the advent of drug-eluting stents has been clinically effective in substantially reducing the rates of major stent-related adverse events compared with bare metal stents, vascular biological problems such as neointimal hyperplasia, delayed re-endothelialization, late stent thrombosis are not eliminated and, increasingly, neoatherosclerosis is the underlying mechanism for very late stent failure. Further understanding regarding the mechanisms underlying the biological responses to stent deployment is therefore required so that new and improved therapies can be developed. This review will discuss the accumulating evidence that the chemokines, small inflammatory proteins, play a role in each key biological process of stent biocompatibility. It will address the chemokine system in its specialized roles in regulating the multiple facets of vascular biocompatibility including neointimal hyperplasia, endothelial progenitor cell (EPC) mobilization and re-endothelialization after vascular injury, platelet activation and thrombosis, as well as neoatherosclerosis. The evidence in this review suggests that chemokine-targeting strategies may be effective in controlling the pathobiological processes that lead to stent failure. Preclinical studies provide evidence that inhibition of specific chemokines and/or broad-spectrum inhibition of the CC-chemokine class prevents neointimal hyperplasia, reduces thrombosis and suppresses the development of neoatherosclerosis. In contrast, however, to these apparent deleterious effects of chemokines on stent biocompatibility, the CXC chemokine, CXCL12, is essential for the mobilization and recruitment of EPCs that make important contributions to re-endothelialization post-stent deployment. This suggests that future chemokine inhibition strategies would need to be correctly targeted so that all key stent biocompatibility areas could be addressed, without compromising important adaptive biological responses.
Inhibition of DNA repair in chronic lymphocytic leukemia: Therapeutic implications
Authors: L. Amrein, R. Aloyz, L. C. Panasci
Journal: Journal of Clinical Oncology (2006)

16513 Background: Chronic lymphocytic leukemia (CLL) is an indolent leukemia in which there is an accumulation of immature malignant B-lymphocytes. While treatment with chlorambucil, a nitrogen mustard analogue or fludarabine can control the disease, eventually all patients become resistant to chlorambucil/fludarabine. Chlorambucil’s cytotoxicity is mediated by the interstrand crosslinks (ICLs) introduced into DNA. In mammalian cells, two main pathways are known to be involved in double strand break(DSB) repair: homologous recombinational repair (HRR) and nonhomologous endjoining (NHEJ). Methods: Our laboratory has demonstrated that resistance to chlorambucil involved accelerated repair of the ICLs associated with enhanced DNA repair, specifically enhanced nonhomologous endjoining (NHEJ) and homologous recombinational repair (HRR). We also recently demonstrated that gleevec inhibition of c-abl with resulting inhibition of Rad51-related HRR sensitizes CLL lymphocytes in vitro to chlorambucil. This exciting result has stimulated the development of a clinical protocol to test this combination in CLL. Furthermore, our laboratory has demonstrated that wortmannin, a nonspecific inhibitor of DNA-PK (a key component of NHEJ) sensitizes CLL lymphocytes to chlorambucil. Results: We are actually evaluating the effect of NU7026, a relatively specific DNA-PK inhibitor, in the sensitivity of CLL cells to chlorambucil. Our results indicate that in a CLL cell line (I83) and primary CLL-lymphocytes chlorambucil plus NU7026 have a synergistic cytotoxic effect. Noteworthy, the NU7026 doses used in combination with chlorambucil were not toxic to the cells when used alone. Moreover, chlorambucil treatment induced DNA-PK nuclear foci which were inhibited by NU7026 suggesting that the synergy of both drugs is mediated by Nu7026-inhibition of DNA-PK. Conclusion: NU7026 plus chlorambucil should be a useful combination to treat CLL. No significant financial relationships to disclose.
SEX-DIFFERENCES IN LEFT VENTRICULAR REMODELLING PATTERN BY 3D ECHOCARDIOGRAPHY IN ASSOCIATION WITH THE LONG-TERM RISK OF ALL-CAUSE MORTALITY: FINDINGS FROM THE SOUTHALL AND BRENT REVISITED (SABRE) STUDY
Authors: Lamia Al Saikhan, Chloe Park, Therese Tillin, Jamil Mayet, Nishi Chaturvedi, Alun Hughes
Journal: Journal of the American College of Cardiology (2020)
Prevalence of Tobacco Use Among Rural-Dwelling Individuals Who Inject Drugs
Authors: Wajiha Z. Akhtar, Marlon P. Mundt, Ruth Koepke, Sarah Krechel, Michael C. Fiore, David W. Seal, Ryan P. Westergaard
Journal: JAMA Network Open (2020)

This cross-sectional study assesses the prevalence of smoking through a multisite survey of individuals aged 15 years or older living in rural Wisconsin who inject drugs.
Oral delivery of Hyperimmune bovine serum antibodies against CS6-expressing enterotoxigenic<i>Escherichia coli</i>as a prophylactic against diarrhea
Authors: KR Talaat, CK Porter, AL Bourgeois, TK Lee, CA Duplessis, M Maciel, RL Gutierrez, B DeNearing, B Adjoodani, R Adkinson, KJ Testa, B Feijoo, AN Alcala, J Brubaker, A Beselman, S Chakraborty, D Sack, J Halpern, S Trop, H Wu, J Jiao, E Sullivan, MS Riddle, SS Joseph, ST Poole, MG Prouty
Journal: Gut Microbes (2020)

Background . Oral administration of bovine antibodies active against enterotoxigenic Escherichia coli (ETEC) have demonstrated safety and efficacy against diarrhea in human challenge trials. The efficacy of bovine serum immunoglobulins (BSIgG) against recombinant colonization factor CS6 or whole cell ETEC strain B7A was assessed against challenge with the CS6-expressing B7A.Methods . This was a randomized, double-blind, placebo-controlled trial in which healthy adults received oral hyperimmune BSIgG anti-CS6, anti-B7A whole cell killed or non-hyperimmune BSIgG (placebo) in a 1:1:1 ratio then challenged with ETEC B7A. Two days pre-challenge, volunteers began a thrice daily, seven day course of immunoprophylaxis. On day 3, subjects received 1 × 1010 CFUs of B7A. Subjects were observed for safety and the primary endpoint of moderate-severe diarrhea (MSD).Results . A total of 59 volunteers received product and underwent ETEC challenge. The BSIgG products were well-tolerated across all subjects. Upon challenge, 14/20 (70%) placebo recipients developed MSD, compared to 12/19 (63%; p = .74) receiving anti-CS6 BSIgG and 7/20 (35%; p = .06) receiving anti-B7A BSIgG. Immune responses to the ETEC infection were modest across all groups.Conclusions . Bovine-derived serum antibodies appear safe and well tolerated. Antibodies derived from cattle immunized with whole cell B7A provided 50% protection against MSD following B7A challenge; however, no protection was observed in subjects receiving serum antibodies targeting CS6. The lack of observed efficacy in this group may be due to low CS6 surface expression on B7A, the high dose challenge inoculum and/or the use of serum derived antibodies versus colostrum-derived antibodies.
Patient Perspectives on the Use of Artificial Intelligence for Skin Cancer Screening
Authors: Caroline A. Nelson, Lourdes Maria Pérez-Chada, Andrew Creadore, Sara Jiayang Li, Kelly Lo, Priya Manjaly, Ashley Bahareh Pournamdari, Elizabeth Tkachenko, John S. Barbieri, Justin M. Ko, Alka V. Menon, Rebecca Ivy Hartman, Arash Mostaghimi
Journal: JAMA Dermatology (2020)

The use of artificial intelligence (AI) is expanding throughout the field of medicine. In dermatology, researchers are evaluating the potential for direct-to-patient and clinician decision-support AI tools to classify skin lesions. Although AI is poised to change how patients engage in health care, patient perspectives remain poorly understood.
RELATIONSHIP BETWEEN HYPERTENSION AND INFARCT SIZE AFTER PRIMARY PCI FOR STEMI: AN INDIVIDUAL PATIENT DATA ANALYSIS OF CARDIAC MAGNETIC RESONANCE IMAGING STUDIES
Authors: Ghazaleh Mehdipoor, Bjorn Redfors, Shmuel Chen, Fotios Gkargkoulas, Zixuan Zhang, Manesh R. Patel, Christopher B. Granger, Erik Magnus Ohman, Akiko Maehara, Ingo Eitel, Ori Ben-Yehuda, Suzanne de Waha-Thiele, Holger Thiele, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2020)
MITRACLIP XTR VS. PASCAL TRANSCATHETER VALVE REPAIR SYSTEM FOR EDGE-TO-EDGE REPAIR OF SEVERE TRICUSPID REGURGITATION
Authors: Daniel Braun, Kornelia Löw, Mathias Orban, Michael Mehr, Jonas Gmeiner, Steffen Massberg, Michael Nabauer, Joerg Hausleiter
Journal: Journal of the American College of Cardiology (2020)
Performance of the high-definition circulating tumor cells (HD-CTC) assay in patients with non-small cell lung cancer (NSCLC).
Authors: Lyudmila Bazhenova, Jorge J. Nieva, Anand Kolatkar, Madelyn Luttgen, Dena Marinucci, Kelly Bethel, Peter Kuhn
Journal: Journal of Clinical Oncology (2012)

e21074 Background: Technologies to isolate and study circulating tumor cells (CTCs) became available in recent years. To date, the most widely employed techniques to detect CTCs use EpCAM based enrichment protocols. However, those assays are only able to find CTCs in a minority of patients with NSCLC, thus limiting its potential applicability. We are reporting performance of a new enrichment-free HD-CTC assay in patients with NSCLC. Methods: This multi-institutional study recruited patients with all stages of NSCLC. Blood was collected at the time of the study entry, 3 weeks, 3m, 6m, 9m, and 12 m. CTCs were identified with enrichment free fluorescent labeling followed by automated digital microscopy. CTCs were physically and morphologically characterized by cytokeratin (CK) intensity, nuclear size, apoptotic changes, and aggregate formation. Cells were classified as HD-CTCs if they met strict morphologic and immunofluorescence characteristics. This assay has been previously validated in 15 normal controls. Results: 106 patients were recruited (I-10, II-3, III-34, IV-59), 78 were chemotherapy naïve. 85%, 79%, and 53% of patients with stages, I+II, III, and IV had detectable HD-CTCs. The chemotherapy naïve cohort had median HD-CTCs of 4.4/mL (range 0–515.6) and a mean of 44.1 (±95.2)/mL. No significant differences were detected in median HD-CTC count between tumor stages (p = 0.32). CK intensity, nuclear size, frequency of apoptosis and aggregate formation was also similar across stages. 28 patients with stage IV disease were analyzed with multiple draws over time. Mean CTC counts were averaged over multiple draws. In each individual patient there was a trend for increased CTC prevalence with advancement of the disease. Median survival was 244 days for patients with ≥5 CTC/mL vs. 304 days for patients with &lt; 5 CTC/mL. HR 4.0, (p=0.0084). Conclusions: The HD-CTC assay can detect CTCs in a high percentage of patients with early and advanced NSCLC. Small subset analysis demonstrated the prognostic value for the enumeration of HD-CTCs. The high prevalence of HD-CTCs across stages could make this assay an ideal candidate for larger scale investigation into prognostic and predictive features of HD-CTCs.
TRANSCATHETER AORTICVALVEREPLACEMENT VERSUS SURGICAL AORTIC VALVE REPLACEMENT INAORTIC STENOSIS WITH CHRONIC CORONARY ARTERY DISEASE: NATIONWIDE INPATIENT ANALYSIS
Authors: Fangcheng Wu, Anand Muthu Krishnan, Isaac Yepes, Akshay Goel, Lindsey Clark, Kevin Buda, Siyi Huang
Journal: Journal of the American College of Cardiology (2020)
Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone combined with high-dose methotrexate plus intrathecal chemotherapy for newly diagnosed intravascular large B-cell lymphoma (PRIMEUR-IVL): a multicentre, single-arm, phase 2 trial
Authors: Kazuyuki Shimada, Motoko Yamaguchi, Yoshiko Atsuta, Kosei Matsue, Keijiro Sato, Shigeru Kusumoto, Hirokazu Nagai, Jun Takizawa, Noriko Fukuhara, Koji Nagafuji, Kana Miyazaki, Eiichi Ohtsuka, Masataka Okamoto, Yasumasa Sugita, Toshiki Uchida, Satoshi Kayukawa, Atsushi Wake, Daisuke Ennishi, Yukio Kondo, Tohru Izumi, Yoshihiro Kin, Kunihiro Tsukasaki, Daigo Hashimoto, Masaaki Yuge, Atsumi Yanagisawa, Yachiyo Kuwatsuka, Satoko Shimada, Yasufumi Masaki, Nozomi Niitsu, Hitoshi Kiyoi, Ritsuro Suzuki, Takashi Tokunaga, Shigeo Nakamura, Tomohiro Kinoshita
Journal: The Lancet Oncology (2020)
Comparative study of micro‐transplantation from <scp>HLA</scp> fully mismatched unrelated and partly matched related donors in acute myeloid leukemia
Authors: Kai‐Xun Hu, Xin Du, Mei Guo, Chang‐Lin Yu, Jian‐Hui Qiao, Qi‐Yun Sun, Hong‐Li Zuo, Bo Cai, Ya‐Jing Huang, Hui‐Sheng Ai, Zheng Dong, Yi Wang
Journal: American Journal of Hematology (2020)

Abstract Micro‐transplantation (MST) by chemotherapy, combined with granulocyte colony‐stimulating factor‐mobilized peripheral blood stem cell (GPBSC) infusion, from an HLA partial matched related donor has shown some encouraging effective therapy for acute myeloid leukemia (AML). However, the outcome of human leukocyte antigen (HLA) fully mismatched unrelated donor‐derived MST in such patients is still unknown. In the present study, we compared the efficacy of HLA fully mismatched unrelated donor‐derived MST, and partly matched related donor‐derived MST, in AML of 126 patients from two centers in China, These patients, aged 16 to 65 years, were given three or four courses of MST, which consisted of a high dosage cytarabine followed by GPBSC from unrelated donor or related donor. There was a statistically significant difference in 3‐year leukemia‐free survival (LFS) and 3‐year overall survival (OS) between the unrelated and the related group. The non‐treatment‐related mortality (NRM) rates of patients, and other adverse complications, were no different in the two groups. In conclusion, unrelated donor‐derived MST is believed to be a safe treatment, with efficacy similar to or higher than related donor‐derived MST. This result provides support for the potential of MST for expanding the donor selection. However, the specific mechanism of action needs further study.
CLINICAL UTILITY OF THE TRIGLYCERIDE-GLUCOSE INDEX, A NOVEL MARKER OF INSULIN RESISTANCE, FOR PREDICTING THE NEOINTIMAL VULNERABILITY AFTER EVEROLIMUS-ELUTING STENT
Authors: Naotaka Akutsu, Daiske Fukamachi, Yasunari Ebuchi, Riku Arai, Suguru Migita, Tomoyuki Morikawa, Takehiro Tamaki, Keisuke Kojima, Nobuhiro Murata, Toshihiko Nishida, Mitsumasa Sudo, Daisuke Kitano, Yasuo Okumura
Journal: Journal of the American College of Cardiology (2020)
Four thoracic cavity compartments caused by bilateral bifid intrathoracic rib
Authors: Xuhong Xue, Sheng Zhao
Journal: Thorax (2020)

A 13-year-old boy who had hump-back was taken to the hospital. The whole spine posteroanterior and lateral radiograph showed failures of segmentation from T5 to T8 vertebra, as well as laminae fusion, diagnosed congenital thoracic kyphoscoliosis. Spinal fusion surgery was suggested because of the potential progress of segmental kyphosis. However, unusual imaging revealed that four thoracic cavity compartments were separated by two deformed ribs extending inferolaterally in bilateral hemithorax (figure 1A).



Figure 1 
Intrathoracic rib. Chest radiograph showing four thoracic cavity compartments separated by two deformed ribs extending inferolaterally in bilateral hemithorax (A). In the coronal CT scan, the focal additional compartment was formed with …
Tetsu Nakamura: Japanese physician and honorary Afghan citizen, who headed Peace Japan Medical Services
Authors: Khyber Nazimi, Akimichi Inaba
Journal: BMJ (2020)

Tetsu Nakamura, a Japanese physician, was killed along with five others during an ambush on the outskirts of Jalalabad, Afghanistan, on 4 December 2019. He was 73. For 30 years, Nakamura worked not only within the traditional role of doctor but more broadly in humanitarian projects to improve the health of the people and the political stability of Afghanistan. For his work, he received the 2003 Ramon Magsaysay award—often referred to as Asia’s Nobel prize—and in 2019 he was given honorary Afghan citizenship.

Nakamura was raised in Fukuoka prefecture on the southernmost island of Kyūshū. He graduated from Kyūshū University School of Medicine in 1973. As a young doctor he left Japan in 1984 to volunteer with Japan Overseas Christian Medical Cooperative Service in Peshawar, Pakistan. There he headed the leprosy unit, but by 1986 was treating the influx of …
REAPPRAISAL OF CARDIAC MAGNETIC RESONANCE IN LEFT VENTRICULAR NON-COMPACTION: NEW INSIGHTS FROM A LARGE, LONGITUDINAL STUDY
Authors: Jay Ramchand, Pooja Podugu, Michael Chetrit, Serge Harb, Alex Milinovich, Brian P. Griffin, Leslie Cho, Scott D. Flamm, Wai Hong Wilson Tang, Deborah Kwon
Journal: Journal of the American College of Cardiology (2020)
Stereotactic body radiation therapy vs. radiofrequency ablation in Asian patients with hepatocellular carcinoma
Authors: Nalee Kim, Jason Cheng, Inkyung Jung, Ja Der Liang, Yu Lueng Shih, Wen-Yen Huang, Tomoki Kimura, Victor H.F. Lee, Zhao Chong Zeng, Ren Zhenggan, Chul Seung Kay, Seok Jae Heo, Jong Yoon Won, Jinsil Seong
Journal: Journal of Hepatology (2020)
Efficacy and safety of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in women with recurrent gynaecological cancer and peritoneal carcinomatosis.
Authors: Marc A Reymond, Wiebke Solass, Urs Giger-Pabst, Dirk Strumberg, Jurgen Zieren, Clemens Tempfer
Journal: Journal of Clinical Oncology (2013)

e16523 Background: Peritoneal carcinomatosis (PC) is common in ovarian (OC) and other gynaecological cancers. We have developed an innovative therapy, Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC), which improves local tumor drug uptake and can be combined with systemic chemotherapy. PIPAC achieves outstanding local biodisponibility with low systemic exposure. Liver and renal toxicity are minimal. The procedure is safe for health workers. We present first results obtained in end-stage PC from gynaecological origin. Methods: Since 1.12.2011 we have performed 18 PIPAC applications in 9 end-stage PC patients with OC (n = 4), papillary (n = 3), tuba (n = 1) and cervix (n = 1) cancer. Mean age was 64.6 ± 16 years. In 4 instances, PIPAC was combined with cytoreductive surgery. Patients were followed-up until Dec, 2012 or until death. Tumor response was assessed by macroscopy (PCI) and microscopy. Results: No intraoperative complication was noted. Mean operating time (PIPAC alone) was 97 ± 20 min. PIPAC could be repeated at 6-weeks intervals (4x: n = 1; 3x: n = 3: 1x: n = 5). In one case, adhesions prevented iterative PIPAC. No adverse event &gt; 2 CTCAE was noted after PIPAC alone. Six patients are alive. Median survival has not been reached after a mean follow-up of 8 months, actuarial survival after one year is 58,3%. Four patients were eligible for response assessment after repeated PIPAC. One showed complete remission (CR), three partial remission (PR). Performance index (Karnofsky) increased from 62 ± 17 % to 82 ± 5 % after therapy. Conclusions: These first results are promising. PIPAC can induce a regression of PC in advanced, therapy-resistant gynaecological cancers. PIPAC is well tolerated and can improve patient’s performance. First survival data are encouraging. PIPAC will now be evaluated in a phase-II clinical trial with cisplatin and doxorubicine (EudraCT 2012-004397-26) in therapy-resistant, recurrent OC.
Prospective study of the impact of using the 21-gene recurrence score assay on clinical decision making in women with estrogen receptor-positive, HER2-negative, early-stage breast cancer in France.
Authors: Joseph Gligorov, Xavier B. Pivot, Herve L. Naman, William Jacot, Dominique Spaeth, Jean-Louis Misset, Remy Largillier, Jean-Loup Sautiere, Anne de Roquancourt, Christophe Pomel, Philippe Rouanet, Roman Rouzier, Frederique Madeleine Penault-Llorca
Journal: Journal of Clinical Oncology (2012)

568^ Background: The 21-gene Oncotype DX Recurrence Score (RS) is a validated assay to help inform the appropriate treatment of estrogen receptor-positive (ER+), early stage breast cancer in the adjuvant setting. Treatment traditions regarding choice of adjuvant treatment vary significantly in different countries. This prospective multicenter study is the first to assess the impact of using the Oncotype DX assay in the French clinical setting. Methods: A total of 100 consecutive patients with ER+, HER2-negative, node negative or pN1 (mi) breast cancer were enrolled. Overall treatment recommendation change, change from chemoendocrine to endocrine alone and change from endocrine alone to chemoendocrine treatment were recorded. Medical oncologists completed questionnaires regarding their confidence in their recommendation before and after knowing the patient’s RS. A preliminary analysis was conducted on the first 92 evaluable patients with data available at the time of abstract submission. Final data will be presented at the meeting. Results: Prior to Oncotype DX 49% of patients were recommended chemoendocrine treatment and 51% endocrine treatment alone. After having the RS, 26% were recommended chemoendocrine treatment and 74% endocrine treatment alone. The overall reduction in chemotherapy recommendation from 49% to 26% was significant (p&lt;0.001). Of patients originally recommended chemoendocrine treatment, 58% were changed to endocrine treatment alone after having the RS. Of patients originally recommended endocrine treatment, 11% were changed to chemoendocrine treatment after receiving the RS. There was a significant improvement in physician confidence in treatment recommendations (p=0.002) when using Oncotype DX. Conclusions: These are the first prospective data regarding the impact of using Oncotype DX in France. Using Oncotype DX was associated with a significant change in treatment decisions and an overall reduction in chemotherapy use. The data are consistent with those presented from Germany, Spain, the UK and the US.