tbuckley/cabot-search huggingface dataset:
Evaluation of combination therapies with MOR00208, an Fc-enhanced humanized CD19 antibody, in models of lymphoma.
Authors: Mark Winderlich, Daniel Ness, Stefan Steidl, Jan Endell
Journal: Journal of Clinical Oncology (2012)

6574 Background: MOR00208 (formerly XmAb5574) is a Fc-engineered humanized anti-CD19 antibody with superior cytotoxicity in a number of in vitro and in vivo models of lymphoma and leukemia, currently being evaluated in patients with relapsed/refractory CLL. Bendamustine (BEN), an alkylating agent, fludarabine (FLU), a purine analogue, and the CD20 antibodies rituximab (RTX) and ofatumumab (OFA) were evaluated for their ability to enhance the cytotoxicity of MOR00208. Methods: Utilizing CD19/CD20+ MEC-1 CLL cells, cytotoxicity was assessed in vitro by flow cytometry. MOR00208 was tested alone and in combination with BEN, FLU, RTX and OFA using peripheral blood mononuclear cells as effector cells. Median survival (MS) was evaluated in a murine model of disseminated lymphoma, using i.v.-administered RAMOS cells (CD19+) and treatment with MOR00208 alone and in combination with FLU. Combinatorial effects were classified according to Chou-Talalay (Pharmacol Rev. 2006 Sep;58(3):621-81). Results: MOR00208-mediated in vitro cytotoxicity was synergistically enhanced by BEN, FLU and the CD20 antibodies irrespective of their different modes of action (Combination Index &lt; 1). In vivo, FLU alone at doses up to the maximum tolerated dose (MTD) did not prolong MS, whereas MOR00208 at 3 mg/kg increased MS by 26% compared to the isotype control. Co-administration of MOR00208 with 125 mg/kg FLU significantly enhanced MS by 65%. Despite its lack of single agent activity, FLU thus significantly enhanced the cytotoxicity of MOR00208. Conclusions: The cytotoxic in vitro activity of MOR00208 on CD19+ B cells was synergistically enhanced by all studied drugs irrespective of their effector mechanisms. In vivo, the activity of MOR00208 in an aggressive lymphoma model was potentiated in combination with FLU. These results provide a mechanistic rationale for MOR00208 drug combinations which warrant further evaluation in clinical trials.
Bilateral pulmonary nodules in a patient with extensive autoimmune disease
Authors: Sachin Patel, Wael Nasser, Rumi Khan, Luis Herrera
Journal: Thorax (2019)

A 64-year-old woman presented to our hospital complaining of generalised fatigue and history of mechanical fall with rib fractures while in Africa. Chest X-ray (CXR) incidentally discovered multiple bilateral pulmonary nodules. She has a history of rheumatoid arthritis on methotrexate, Hashimoto’s thyroiditis, Sjogren’s syndrome (SS) and psoriatic arthritis on immunotherapy. She denied symptoms of cough, chest pain, dyspnoea, weight loss, night sweats, fever or haemoptysis. She denied smoking, alcohol consumption, illicit drug use and environmental exposures. She had a family history of lymphoma in sister but no personal/family history of arteriovenous malformations, hamartomas or vasculitis. CXR conducted 3 years prior showed no lesions. She was up-to-date with breast screening but refused colonoscopy. Physical exam was unremarkable.

On arrival to USA, chest CT confirmed bilateral nodules with lower lung predominance (figure 1) and positron emission tomography scan demonstrated hypermetabolic activity of the nodules. Lab work—blood count, metabolic profile, urinalysis, immunoglobulins, HIV, serum/urine protein electrophoresis and …
Response to ‘Augmented vs. artificial intelligence for stratification of patients with myositis’ by Mahler <i>et al</i>
Authors: Alain Meyer, Lionel Spielmann, François Séverac
Journal: Annals of the Rheumatic Diseases (2019)

We thank Mahler et al for their comment1 on our work in which we used hierarchical clustering on principal components to define clinically meaningful subgroups of patients with anti-Ku antibodies.2 

Mahler et al argue for the use of machine learning alongside expert decision, thus relying on augmented judgement in making the final decision on patient stratification. We share this view.

In this regard, we disagree with the statement according to which the hierarchical clustering on principal components applied to 1000 observations with a multivariate normal distribution proposed by Pinal-Fernandez and Mammen3 and the hierarchical clustering on principal components applied to our observations from 42 anti-Ku patients yielded similar results.

As Mahler et al stated, clustering …
Nonpegylated liposome-encapsulated doxorubicin (NPLED) and cyclophosphamide in the treatment of platinum-resistant ovarian cancer: Final results of a phase II study.
Authors: Daniela Sambataro, Melania Caruso, Concetta Di Blasi, Giuseppe Lavenia, Salvatore Asero, Placido Amadio, Marco Mattina, Giovanni Burrafato, Laura Longhitano, Stefania Rapisardi, Stefano Sergio Cordio, Giuseppe Ettore, Roberto Bordonaro
Journal: Journal of Clinical Oncology (2012)

e15544 Background: Platinum resistant-refractory ovarian cancer (PRROC) patients have a poor outcome; single-agent therapy is still the gold standard, with overall response rate lesser than 20% and progression-free-survival is not higher than 4 months. Methods: We tested safety and activity of a two-drugs-regimen containing NPLED and cyclophosphamide in a phase II open label study. From October 2007 to October 2011 thirty-two patients with platinum-resistant/refractory disease were enrolled. Enrolled patients were pretreated with a median number of 2 lines of chemotherapy, ranging from 1 to 5. NPLED and cyclophosphamide were administered at the dose of 60 mg. and 600 mg p.s.m. respectively. Results: Patients received a median number of three cycles of chemotherapy. A total of 145 cycles were administered: as G3 toxicities we registered emesis (6%), diaorrhea (3%), asthenia, and alopecia. No grade 4 adverse events occurred. Among the 30 patients evaluable for response we observed 5 (17%) partial responses and 10 (33%) stable diseases. The median progression-free-survival was 13 weeks and the median survival was 46 weeks. Conclusions: These results are similar to other data reported in literature. In conclusion we may affirm that the association of NPLED and cyclophosphamide is active and safe when administered in PRROC, but it don’t modify the prognosis of this subset of patients.
Dual intracavitary therapy for pleural infections: leaving reluctance behind
Authors: José M. Porcel
Journal: European Respiratory Journal (2019)

The optimal management of complicated parapneumonic effusions and empyemas remains undefined. Over the past two decades, three guidelines from scientific societies have been developed to aid treatment selection in this setting [1–3]. In 2000, the American College of Chest Physicians stated that intrapleural fibrinolytics, video-assisted thoracoscopic surgery (VATS) and surgery (thoracotomy with or without decortication) were all acceptable approaches for managing patients who meet any of the following characteristics [1]: pus (category 4 effusions or, strictly speaking, empyemas), large (at least half of the hemithorax) or loculated effusions, positive pleural fluid cultures or Gram stains, or a fluid pH <7.20 (the last three conditions integrating category 3 effusions). Intrapleural tPA/DNase therapy is cost-effective for the management of complicated parapneumonic effusions and empyemas <http://bit.ly/2Lv0Kg9>
An analysis of the temporal, age, and gender trends in human papillomavirus virus (HPV)-related versus non-HPV-related head and neck cancers (HNC) in Alberta, Canada.
Authors: Desiree Hao, Harold Y. Lau, Longlong Huang, Corinne M. Doll, Joseph C. Dort, Lorraine Shack
Journal: Journal of Clinical Oncology (2013)

e12505 Background: Recent epidemiologic studies have suggested that the incidence of HPV-associated HNC is increasing. This study assessed temporal, age-specific and gender specific changes in cancer incidence for HPV- versus non-HPV associated HNC compared with other HPV versus non-HPV associated malignancies in a population-based setting. Methods: We used the Alberta Cancer Registry, a population-based registry of all cancers diagnosed in the province of Alberta, Canada (population est. 3.6 million), to identify patients diagnosed with cancers of the oropharynx, cervix, vulva, vagina, anus, and penis (HPV-associated group) and compared this with non-oropharyngeal cancers of the head and neck and lung cancer (non-HPV associated, modifiable risk group) between January 1, 1975 and December 31, 2009. The age-standardized incidence rates (ASIR) for each cancer by gender and age-specific incidence was estimated with the annual percentage change (APC) assessed using Joinpoint regression. Results: The ASIR for oropharyngeal cancers (OPC) increased over time for both men (APC 3.5) and women (APC 1.5) with rapid increases seen in men under 35 (APC 27.3). Non-oropharyngeal squamous cell carcinomas of the head and neck had a higher ASIR overall with moderate temporal increases (APC 2.5) and age-specific increases highest in those aged 55 to 74. ASIR for anal canal cancers also increased over time, with greater increases amongst younger females, in contrast to OPC. By comparison, the ASIR of cervix cancer declined with more significant decreases in younger females; while the rates of other HPV-associated cancers (vulva, vagina, penile) showed little change. The ASIR for lung cancer decreased after 1987 (APC -1.5) for men and continued to moderately increase for women. Conclusions: Our findings suggest the greatest increases in OPC are occurring in younger men. Programs of HPV prevention such as vaccination should be explored to reduce the incidence of OPC in males.
Abstract #1188: KISS1 metastasis suppression may be partially due to modulation of Wnt signaling through SNAIL
Authors: Lewis Stafford, Kedar Vaidya, Douglas Hurst, Danny Welch
Journal: Cancer Research (2009)

Melanoma is the most deadly type of skin cancer, largely because of its predilection for metastasis. KISS1 is a metastasis suppressor that minimally affects primary tumor growth, but inhibits cells that have disseminated from proliferating and colonizing secondary sites by maintaining them in state of dormancy. However, the molecular mechanisms by which KISS1 accomplishes this are not known. We hypothesized that KISS1 alters expression of genes that affect migration, invasion and dormancy by affecting transcription factor. Re-expression of KISS1 in C8161.9 human melanoma cells did not alter TWIST expression, but there was a dramatic (80%) decrease in SNAIL expression. Concomitant with decreased SNAIL were decreased expression of downstream pro-angiogenic cytokine IL-8 and VEGF, decreased phosphorylation of upstream signaling molecules GSK3beta and beta-catenin, which are both components of the canonical Wnt/beta-catenin signaling pathway. There was no change in the expression of Wnt5a, which is part of the non-canonical Wnt pathway. These results suggest that the metastasis inhibition involves alterations in signaling through the canonical Wnt signaling pathway. In contrast, C8161.9 cells expressing a mutant KISS1 which lacks the secretion signal (does not suppress metastasis) exhibited no changes in SNAIL expression, IL-8, VEGF, phospho-GSK3beta or phospho-beta-catenin. Taken together, these data suggest that KISS1 exerts some of its anti-metastatic effects, in part, by modulation of SNAIL signaling through the Wnt/beta-catenin pathway. Support: CA87728 and National Foundation for Cancer Research  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1188.
Prognostic impact of c-Met/phospho-Met, and topoisomerase I in small cell lung cancer.
Authors: Hideko Ikeda, Hayato Koba, Koji Kurokawa, Shingo Nishikawa, Tomoyuki Araya, Yuichi Tambo, Asao Sakai, Takashi Sone, Junya Fukuoka, Kazuo Kasahara
Journal: Journal of Clinical Oncology (2012)

e17540 Background: The hepatocyte growth factor/MET pathway has been shown to cause tumor progression in several types of carcinomas. We reported that c-Met up-regulated topoisomease I (Topo I) in non-small cell lung cancer cell lines (submitted for publication). The aims of this study were 1) to examine the prognostic influence of c-MET/phospho-MET (p-Met), or Topo I expression and 2) to elucidate correlation between c-Met/p-Met expression and Topo I expression in small cell lung cancer (SCLC). Methods: This retrospective study included 72 SCLC patients (pts) with available tumor tissue from primary lung tumor or metastatic lesions and clinical data including survival. We performed immunohistochemistry to detect c-MET/phospho-MET and Topo I expression. Results: Tumor tissues were obtained from 72 SCLC pts. Sixty-six pts, (51 male, 15 female, median age 67.5 range 43-91, LD/ED 38/28, PS0,1/2,3,4 57/9) were evaluated. c-Met overexpression was seen in 40.9%, p-Met in 74.2%, and Topo I expression in 59.1%, respectively. High expression of Topo I associated with lower response rate (RR) (96.7% in low group vs 78.4% in high group, p=0.029) and shorter progression-free survival (PFS) (65W vs 39W, p=0.040) but did not correlate with overall survival (OS). Phosphorylation of Met protein did not correlate with RR, PFS or OS. Interestingly, intensity of p-Met significantly correlated with Topo I expression (p=0.048). High expression of c-Met protein did not associated with RR or PFS but significantly associated with shorter OS (high 53W, low 95W, p=0.018). Multivariate analysis which included c-Met, stage, PS, and age resulted that c-Met was an independent prognostic factor for OS of pts with SCLC (HR; 2.144, 95% confidence interval 1.162-3.956, p=0.015). Conclusions: This study suggested c-Met high expression was an independent prognostic factor, and Topo I was up-regulated by Met in SCLC.
Infographic. Prenatal physical activity: baby steps for better health
Authors: Margie H Davenport, Trevor Horbachewsky, Michael Brown, Nicole Graham, Jocelyn Love, Michelle Mottola, Stephanie-May Ruchat
Journal: British Journal of Sports Medicine (2019)

The Society of Obstetricians and Gynaecologists of Canada/Canadian Society for Exercise Physiology 2019 Canadian guideline for physical activity throughout pregnancy provides evidence-based recommendations for pregnant women to optimise maternal/fetal health.1–4 It was developed by a pan-Canadian panel of clinicians, exercise professionals, researchers and methodologists following rigorous, gold-standard methodology for guideline development (Appraisal of Guidelines for Research and Evaluation II instrument) and Grading of Recommendations Assessment, Development and Evaluation system. The recommendations within this document are based on an exhaustive review of the literature distilled into 12 systematic reviews examining the influence of physical activity during pregnancy …
Assessment of Rapid Response Teams at Top-Performing Hospitals for In-Hospital Cardiac Arrest
Authors: Kimberly Dukes, Jacinda L. Bunch, Paul S. Chan, Timothy C. Guetterman, Jessica L. Lehrich, Brad Trumpower, Molly Harrod, Sarah L. Krein, Joan E. Kellenberg, Heather Schacht Reisinger, Steven L. Kronick, Theodore J. Iwashyna, Brahmajee K. Nallamothu, Saket Girotra
Journal: JAMA Internal Medicine (2019)

Rapid response teams (RRTs) are foundational to hospital response to deteriorating conditions of patients. However, little is known about differences in RRT organization and function across top-performing and non-top-performing hospitals for in-hospital cardiac arrest (IHCA) care.To evaluate differences in design and implementation of RRTs at top-performing and non-top-performing sites for survival of IHCA, which is known to be associated with hospital performance on IHCA incidence.A qualitative analysis was performed of data from semistructured interviews of 158 hospital staff members (nurses, physicians, administrators, and staff) during site visits to 9 hospitals participating in the Get With The Guidelines-Resuscitation program and consistently ranked in the top, middle, and bottom quartiles for IHCA survival during 2012-2014. Site visits were conducted from April 19, 2016, to July 27, 2017. Data analysis was completed in January 2019.Semistructured in-depth interviews were performed and thematic analysis was conducted on strategies for IHCA prevention, including RRT roles and responsibilities.Of the 158 participants, 72 were nurses (45.6%), 27 physicians (17.1%), 27 clinical staff (17.1%), and 32 administrators (20.3%). Between 12 and 30 people at each hospital participated in interviews. Differences in RRTs at top-performing and non-top-performing sites were found in the following 4 domains: team design and composition, RRT engagement in surveillance of at-risk patients, empowerment of bedside nurses to activate the RRT, and collaboration with bedside nurses during and after a rapid response. At top-performing hospitals, RRTs were typically staffed with dedicated team members without competing clinical responsibilities, who provided expertise to bedside nurses in managing patients who were at risk for deterioration, and collaborated with nurses during and after a rapid response. Bedside nurses were empowered to activate RRTs based on their judgment and experience without fear of reprisal from physicians or hospital staff. In contrast, RRT members at non-top-performing hospitals had competing clinical responsibilities and were generally less engaged with bedside nurses. Nurses at non-top-performing hospitals reported concerns about potential consequences from activating the RRT.This qualitative study's findings suggest that top-performing hospitals feature RRTs with dedicated staff without competing clinical responsibilities, that work collaboratively with bedside nurses, and that can be activated without fear of reprisal. These findings provide unique insights into RRTs at hospitals with better IHCA outcomes.
Soft-tissue injuries simply need PEACE and LOVE
Authors: Blaise Dubois, Jean-Francois Esculier
Journal: British Journal of Sports Medicine (2019)

Rehabilitation of soft-tissue injuries can be complex. Over the years, acronyms guiding their management have evolved from ICE to RICE , then on to PRICE and POLICE .1 Although widely known, these previous acronyms focus on acute management, unfortunately ignoring subacute and chronic stages of tissue healing. Our contemporary acronyms encompass the rehabilitation continuum from immediate care ( PEACE ) to subsequent management ( LOVE ). PEACE and LOVE (figure 1) outline the importance of educating patients and addressing psychosocial factors to enhance recovery. While anti-inflammatories show benefits on pain and function, our acronyms flag their potential harmful effects on optimal tissue repair. We suggest that they may not be included in the standard management of soft-tissue injuries.



Figure 1 
PEACE and LOVE acronyms.



### P for protect

Unload or restrict movement for 1–3 days to minimise bleeding, prevent distension of injured fibres and reduce the risk of aggravating the injury. Rest should be minimised as prolonged rest can compromise tissue strength and quality.1 Pain signals should guide the cessation of protection.

### E for elevate

Elevate the limb higher …
The addition of fluoxetine to cognitive behavioural therapy for youth depression (YoDA-C): a randomised, double-blind, placebo-controlled, multicentre clinical trial
Authors: Christopher G Davey, Andrew M Chanen, Sarah E Hetrick, Sue M Cotton, Aswin Ratheesh, Günter P Amminger, John Koutsogiannis, Mark Phelan, Edward Mullen, Ben J Harrison, Simon Rice, Alexendra G Parker, Olivia M Dean, Amber Weller, Melissa Kerr, Amelia L Quinn, Lisa Catania, Nikolaos Kazantzis, Patrick D McGorry, Michael Berk
Journal: The Lancet Psychiatry (2019)
Clinical significance and prognostic impact of CD133 expression in rectal cancer treated with preoperative radiochemotherapy.
Authors: Thilo Sprenger, Lena-Christin Conradi, Tim Beissbarth, Kia Homayounfar, Josef Rüschoff, Claus Rödel, B. Michael Ghadimi, Heinz Becker, Franz Rödel, Torsten Liersch
Journal: Journal of Clinical Oncology (2012)

e14161 Background: CD133 has been described as a potential stem cell marker in colorectal cancer and to be associated with higher tumorigenic potential and resistance to radiochemotherapy (RCT). In this study the expression of CD133 was evaluated in pre-RCT tumor biopsies and the corresponding post-RCT surgical specimens of locally advanced rectal cancer patients and correlated to histopathological features and clinical follow-up. Methods: 127 patients with UICC (Union contre le Cancer) II/III rectal cancer treated with preoperative 5-FU based RCT within the German Rectal Cancer Trials were investigated. Pre- and post-RCT CD133 expression levels were determined using immunhistochemistry and correlated with histopathologic parameters, tumor regression grade, cancer recurrence and survival. Results: As compared to pre-RCT biopsies we observed a significantly higher CD133 expression in tumor specimens (p=0.01). There was, however, no correlation for both biopsies and tumor specimens between CD133 expression levels, histopathological features and survival. In matched analyses of corresponding biopsy/tumor pairs, patients with a decreased fraction of CD133+ cells after preoperative RCT showed significantly lower residual tumor stages (p=0.03) and higher histopathological tumor regression (p&lt;0.01). Moreover, these patients had a significantly improved disease-free (DFS) and cancer-specific overall survival (CSS) in uni- (p&lt;0.001) and multivariate analyses (p=0.001), respective. Conclusions: Enrichment of CD133+ cancer cells during preoperative RCT is correlated with minor local tumor response, distant cancer recurrence and survival. Up-regulation of intratumoral CD133 expression – more than pre- and post-RCT CD133 levels – plays an important role in therapy resistance, tumor progression and metastasis in rectal cancers undergoing neoadjuvant RCT.
Multiple Pathologic Pathways to Dementia in Football Players With Chronic Traumatic Encephalopathy
Authors: Julie A. Schneider
Journal: JAMA Neurology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Pregnancy and Delivery After PRRT Without Sequelae
Authors: Jingjing Zhang, Harshad R. Kulkarni, Coline Lehmann, Aviral Singh, Richard P. Baum
Journal: Clinical Nuclear Medicine (2018)

Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogues has been proven to be very useful in the management of advanced, well-differentiated neuroendocrine neoplasms (NENs). We present here the pregnancy outcome in a NEN patient, who naturally conceived and gave birth to a healthy baby, after 4 cycles of PRRT administering a cumulative radioactivity of 27.1 GBq. This case underlines that pregnancy and birth without sequelae are possible in patients with NEN who have been treated with PRRT and offers a definitive prospect for patients of reproductive age group who plan conception despite having received or due to undergo PRRT.