tbuckley/cabot-search huggingface dataset:
Adherence to clinical practice guidelines for adjuvant chemotherapy for colorectal cancer in Uruguay: A population-based study.
Authors: Santiago Fontes, Ana Marín-Jiménez, Megan Berry, Mauricio Cuello, Juan Carlos Sánchez, Graciela Reyes, Gabriel David Krygier
Journal: Journal of Clinical Oncology (2021)

53 Background: Despite surgery, the 5-year risk of systemic recurrence of colorectal cancer (CRC) in the absence of any further therapy is approximately 50 % for those with lymph node involvement and 20 ─ 30 % if the lymph nodes are negative. Adjuvant chemotherapy contributes to improved disease-free and overall survival for node-positive (stage III) or high-risk node negative (stage IIB) colon cancer. Similar benefits are observed for adjuvant chemoradiotherapy in rectal cancer. Previous research shows varied rates of adherence to published adjuvant chemotherapy Clinical Practice Guidelines (CPGs) for CRC, although population-based data is scarce. Purpose: The aim of this analysis was to assess adherence rates to adjuvant chemotherapy prescription within 16 weeks of surgery according to local and international CPGs for CRC patients treated with curative intent between 2008 and 2019 at the Uruguayan National Cancer Institute. Data regarding factors associated with chemotherapy receipt beyond 16 weeks from surgery and chemotherapy non receipt was also retrieved and analysed. Methods: We retrospectively reviewed medical and pathology reports of 833 patients diagnosed with CRC at our institution. Patients with stages IIB or III CRC who underwent curative-intent surgery were identified and included in the present analysis. A 16-week benchmark timeline for treatment initiation from date of surgery was considered. Fisher’s exact test was used to determine factors independently associated with receipt of chemotherapy and meeting the 16-week benchmark (p 0.05). Results: A total of 400 patients were identified of which 72% had peritoneal colorectal tumors and 28% had sub-peritoneal rectal tumors. Approximately 70% of the latter group received neoadjuvant chemo-radiotherapy. Considering the total cohort, 61% received adjuvant chemotherapy. Factors predicting chemotherapy receipt in the peritoneal colorectal group were age ≤ 70 and stage III disease. In the sub-peritoneal rectal group no significant effect was found. The 16-week benchmark was met in 72% (175) of those receiving chemotherapy and 70.6% (167) completed 6 months of systemic adjuvant treatment. A total of 156 patients (39%) did not receive adjuvant chemotherapy. The factors predicting chemotherapy non receipt were age &gt; 70 and stage IIB in the peritoneal colorectal group. Conclusions: This analysis of adherence to CPGs identified several factors associated with chemotherapy non receipt and chemotherapy receipt outside of timeline benchmarks from date of curative-intent surgery in Montevideo, Uruguay. The two main factors significantly associated with chemotherapy non receipt were advanced age and lower disease stage. To our knowledge, our data is the first to elucidate these specific factors in the Uruguayan CRC patient population.
Incarceration and Social Death — Restoring Humanity in the Clinical Encounter
Authors: Bisan A. Salhi, Anwar D. Osborne
Journal: New England Journal of Medicine (2021)

Hospitals may intersect with the carceral system and participate in processes of "social death," in which a person is treated as a nonperson and discounted in social terms. But the clinical encounter can resist rather than reinforce the process of social death.
SP0163 Patient partner program
Authors: J Zasterova
Journal: Annals of the Rheumatic Diseases (2001)

<h3></h3> Ms. Zasterova describes her participation in the Patient Partner program sponsored by the Searle Company. The aim of the program is to train people suffering from rheumatic arthritis and osteoarthritis so that they could become teachers/advisors to other patients with rheumatic disease and so start continuing rounds of patient-to-patient teaching. The training consists of: Regular meetings Lectures on medicaments, psychology, rehabilitation, etc. Practical presentation of medical aids Teaching materials Final test of knowledge gained The program not only provides information that helps them understand and influence their own disease, but also engages patients in sharing the knowledge and encourages patients to mutual help.
Telotristat ethyl to enhance cytotoxic chemotherapy response in preclinical cholangiocarcinoma models.
Authors: Niranjan Awasthi, Margaret Schwarz, Roderich E. Schwarz
Journal: Journal of Clinical Oncology (2021)

331 Background: Cholangiocarcinoma (CCA) is the second-most common primary liver cancer after hepatocellular carcinoma. It has a poor prognosis with a 5-year survival rate of 5-15%. The current standard first-line therapy for advanced unresectable CCA is a combination of gemcitabine and cisplatin (GemCis) chemotherapy that leads to a median survival of 6-12 months. Nanoparticle albumin-bound paclitaxel ( nab-paclitaxel, NPT) is an approved therapy for breast, NSCLC and pancreatic cancer. Elevated levels of serotonin have been reported in CCA that has protumorigenic activity. We tested the hypothesis that telotristat ethyl (TE), an inhibitor of serotonin biosynthesis, has antitumor activity in CCA and it augments GemCis and nab-paclitaxel response in preclinical CCA models. Methods: Tumor growth experiments were performed in mice subcutaneous CCA intrahepatic CCLP-1 xenografts, extrahepatic TFK-1 xenografts and patient-derived xenografts. Animal survival studies were performed using human CCA intrahepatic CCLP-1 cells in the peritoneal dissemination model in NOD/SCID mice. Results: In intrahepatic CCLP-1 subcutaneous xenografts, compared with controls, reduction in tumor growth was observed by TE (53%), GemCis (53%) or NPT (69%). The combination of TE with GemCis or NPT exhibited an additive tumor growth inhibition response, GemCis+TE (85%) and NPT+TE (90%). In extrahepatic TFK-1 subcutaneous xenografts, TE led to a significant reduction in tumor growth (51%), while GemCis and NPT reduced tumor growth by 37% and 56%, respectively. Again, an additive tumor growth inhibition effect was observed by the addition of TE to chemotherapy, GemCis+TE (67%) and NPT+TE (74%). In CCA patient-derived subcutaneous xenografts, GemCis caused the greatest tumor growth reduction (80%) followed by NPT (57%) and TE (40%). Combinations increased tumor inhibition further: GemCis+TE (95%) and NPT+TE (91%). Mouse survival in peritoneal dissemination xenografts was only marginally enhanced by TE (11%) or GemCis (9%) while NPT led to a substantial extension (60%). Interestingly, the combination of TE with GemCis or NPT demonstrated a further extension in mice survival: GemCis+TE (26%) and NPT+TE (68%). Conclusions: TE had antitumor activity and it enhanced chemotherapy effects in several CCA preclinical models indicating that this therapeutic combination has the potential to ameliorate clinical therapy for CCAs of different origin.
Network-based systems pharmacology reveals heterogeneity in LCK and BCL2 signaling and therapeutic sensitivity of T-cell acute lymphoblastic leukemia
Authors: Yoshihiro Gocho, Jingjing Liu, Jianzhong Hu, Wentao Yang, Neekesh V. Dharia, Jingliao Zhang, Hao Shi, Guoqing Du, August John, Ting-Nien Lin, Jeremy Hunt, Xin Huang, Bensheng Ju, Lauren Rowland, Lei Shi, Dylan Maxwell, Brandon Smart, Kristine R. Crews, Wenjian Yang, Kohei Hagiwara, Yingchi Zhang, Kathryn Roberts, Hong Wang, Elias Jabbour, Wendy Stock, Bartholomew Eisfelder, Elisabeth Paietta, Scott Newman, Giovanni Roti, Mark Litzow, John Easton, Jinghui Zhang, Junmin Peng, Hongbo Chi, Stanley Pounds, Mary V. Relling, Hiroto Inaba, Xiaofan Zhu, Steven Kornblau, Ching-Hon Pui, Marina Konopleva, David Teachey, Charles G. Mullighan, Kimberly Stegmaier, William E. Evans, Jiyang Yu, Jun J. Yang
Journal: Nature Cancer (2021)
FRI0188 Diastolic dysfunction in patients with scleroderma: a tissue doppler study
Authors: A Dinc, M Uzun, S Pay, I Simsek, F Kilicarslan, H Erdem
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Systemic sclerosis may involve myocardium and brings about myocardial fibrosis. <h3>Objectives</h3> In our study, left ventricular diastolic functions were evaluated with the tissue Doppler echocardiography, a newer and more sensitive method than others. <h3>Methods</h3> Standard and tissue Doppler echocardiography were applied to 11 patients with systemic sclerosis. Systolic and valve functions were evaluated with standard echocardiography and then the signals obtained from the lateral section of mitral annulus were analysed with pulse wave tissue Doppler echocardiography. Left ventricular diastolic functions were assessed by calculating early wave (E), atrial wave (A) and E/A ratio of these signals. <h3>Results</h3> The impairment of left ventricular diastolic functions was determined in 4 patients. This finding was not related to the duration of disease and the spread of involvement. All patients have normal ejection fractions. <h3>Conclusion</h3> Left ventricular diastolic dysfunction is a newly defined special feature for cardiac involvement of systemic sclerosis. This finding may be due to myocardial ischemia, fibrosis, or both of them. However, larger studies are necessary to evaluate the prognostic importance of this finding.
Disease-mediated ecosystem services: Pathogens, plants, and people
Authors: Rachel E. Paseka, Lauren A. White, Dedmer B. Van de Waal, Alex T. Strauss, Angélica L. González, Rebecca A. Everett, Angela Peace, Eric W. Seabloom, Thijs Frenken, Elizabeth T. Borer
Journal: Trends in Ecology & Evolution (2020)
Abstract 12548: Cardioselective Galectin-3 Overexpression in Mice Activates MAPK/ERK1/2 Signaling and Induces Myocardial Fibrosis
Authors: Swati D Sonkawade, Gen Suzuki, Shirley Xu, Kristi Kc, Saraswati Pokharel, Umesh C Sharma
Journal: Circulation (2019)

Introduction: Galectin-3 (gal-3) is a macrophage-released chimeric molecule implicated in cardiac fibrosis. Here we report the first genetically engineered mouse model of cardioselective gal-3 over...
Characterization and Function of Tumor Necrosis Factor and Interleukin‐6–Induced Osteoclasts in Rheumatoid Arthritis
Authors: Kazuhiro Yokota, Kojiro Sato, Takashi Miyazaki, Yoshimi Aizaki, Shinya Tanaka, Miyoko Sekikawa, Noritsune Kozu, Yuho Kadono, Hiromi Oda, Toshihide Mimura
Journal: Arthritis & Rheumatology (2021)

Objective We have previously reported that stimulation of mouse bone marrow–derived macrophages with tumor necrosis factor (TNF) and interleukin‐6 (IL‐6) induces differentiation of osteoclast‐like cells. We undertook this study to clarify the characterization and function of human TNF and IL‐6–induced osteoclasts using peripheral blood collected from patients with rheumatoid arthritis (RA) and healthy donors. Methods Peripheral blood monocytes were cultured with a combination of TNF and IL‐6, TNF alone, IL‐6 alone, or with RANKL, and their bone resorption ability was evaluated. Expression levels of NFATc1, proinflammatory cytokines, and matrix metalloproteinase 3 were analyzed. The effects of NFAT inhibitor and JAK inhibitor were examined. Furthermore, the relationship between the number of TNF and IL‐6–induced osteoclasts or RANKL‐induced osteoclasts differentiated from peripheral blood mononuclear cells (PBMCs) in patients with RA and the modified total Sharp score (mTSS) or whole‐body bone mineral density (BMD) was examined. Results Peripheral blood monocytes stimulated with a TNF and IL‐6–induced osteoclasts were shown to demonstrate the ability to absorb bone matrix. Cell differentiation was not inhibited by the addition of osteoprotegerin. Stimulation with a combination of TNF and IL‐6 promoted NFATc1 expression, whereas the NFAT and JAK inhibitors prevented TNF and IL‐6–induced osteoclast formation. Expression levels of IL1β , TNF , IL12p40 , and MMP3 were significantly increased in TNF and IL‐6–induced osteoclasts, but not in RANKL‐induced osteoclasts. The number of TNF and IL‐6–induced osteoclasts differentiated from PBMCs in patients with RA positively correlated with the mTSS, whereas RANKL‐induced osteoclast numbers negatively correlated with the whole‐body BMD of the same patients. Conclusion Our results demonstrate that TNF and IL‐6–induced osteoclasts may contribute to the pathology of inflammatory arthritis associated with joint destruction, such as RA.
Safety and efficacy of anti–PD-1 antibody dostarlimab in patients (pts) with mismatch repair-deficient (dMMR) solid cancers: Results from GARNET study.
Authors: Thierry Andre, Dominique Berton, Giuseppe Curigliano, Susan Ellard, Jose Manuel Trigo Pérez, Hendrik-Tobias Arkenau, Cyril Abdeddaim, Victor Moreno, Wei Guo, Ellie Im, Naureen Starling
Journal: Journal of Clinical Oncology (2021)

9 Background: Dostarlimab is a humanized anti–PD-1 monoclonal antibody that binds the PD-1 receptor, blocking interaction with ligands PD-L1 and PD-L2. The ongoing phase 1 GARNET study (NCT02715284) is evaluating dostarlimab in pts with advanced solid tumors. Here we present safety and efficacy data from cohort F. Methods: Cohort F of the GARNET trial enrolled pts with dMMR or POLEmut non-endometrial solid tumors; the majority were gastrointestinal (GI) in origin. Pts must have progressed per blinded independent central review (BICR) following prior systemic therapy for advanced disease and had dMMR status by local immunohistochemistry. Pts received 500 mg dostarlimab Q3W for 4 cycles and 1000 mg Q6W until discontinuation. Objective response rate (ORR) and duration of response (DOR) were assessed by BICR per RECIST v1.1. Pts were included in the efficacy analysis if they received ≥1 dose of dostarlimab, had measurable disease at baseline, and 6 mo of follow up. All pts who received ≥1 dose were included in the safety analysis. Results: 144 pts were included in the safety analysis, with 106 dMMR pts in the efficacy analysis (1 POLEmut pt with a confirmed PR was not included in this population). Of the 106 pts, 99 (93.4%) had GI tumors. Confirmed ORR in dMMR pts was 38.7% (95% CI: 29.4, 48.6), with a complete response rate of 7.5%. ORR was consistent across tumor type (Table). At the data cutoff, median duration of follow-up (n = 107; dMMR and POLEmut pts) was 12.4 months and median DOR was not reached. The Kaplan–Meier estimated probability of maintaining response at 12 and 18 months was 91.0% and 80.9% respectively. Treatment-related adverse events (TRAEs) were reported in 68.8% of pts; 8.3% of pts experienced at least 1 grade ≥3 TRAE. The most common was lipase increased in 2 (1.4%) pts. Treatment-related serious AEs (SAEs) were reported in 6 (5.5%) pts, and 2 pts (1.8%) discontinued dostarlimab due to a TRAE. No deaths were attributed to dostarlimab. Conclusions: Dostarlimab demonstrated durable antitumor activity in a cohort of dMMR solid tumor pts, the majority of whom had GI cancers. The safety profile was consistent with other cohorts in GARNET, with immune-related TRAEs infrequent and low grade. Clinical trial information: NCT02715284. [Table: see text]
THU0180 Identifying rapid radiographic progressors in rheumatoid arthritis
Authors: JB Wong, CJ Wong, PL Van Riel, JM Hazes, FC Breedveld, DM Van der Heijde, BG Feagan
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Mounting evidence suggests that radiographically progressive disease identifies rheumatoid arthritis patients at higher risk for developing future disability. Hand and foot radiographs, however, incur additional expense and have not become a part of routine practice. <h3>Objectives</h3> To determine if clinical parameters can be used to identify patients with radiographic progression. <h3>Methods</h3> In 2 Dutch cohorts of early rheumatoid arthritis patients from Leiden and Nijmegen, 279 patients had year 2 or 3 radiographs (mean age 50.5 years, 76.7% women, 71.7% RF+, 60.1% HLA DR4+). Using the OMERACT definition, radiographic progression was defined as exceeding the smallest detectable difference (SDD) or 15 modified Sharp units. Because x-rays were done after 2 or 3 years from RA onset, we used the annual radiographic progression rate to define progressors (&gt;7.5) vs non-progressors ( <h3>Results</h3> In this cohort, 199 of the 279 patients (71%) were radiographic ?progressors? after 2 – 3 years of RA. Univariate analysis showed that older age, RF+, higher Disease Activity Score (DAS) and Ritchie articular index (all p &lt; 0.03) were associated with radiographic progression. In the multivariate model, RF positivity (OR 4.78, CI 2.32 – 9.86), older age (OR 1.75 per 10 years, CI 1.36 – 2.27) and higher DAS (OR 1.88, CI 1.32 – 2.69) remained significant. The area under the ROC was 0.81. The resulting sensitivity (SEN) and specificity (SP) values using the following cutpoints were (cutpoint = SEN/SP): 0.50 = 94/48, 0.60 = 89/60, 0.70 = 81/68, 0.80 = 64/79. Thus, treating all patients with predicted probabilities above 0.50 would miss 6% of the radiologic progressors and result in treatment of 52% of the non-progressors. Or treating only patients with predicted probabilities above 0.80 would miss 36% of the progressors and treat 21% of the non-progressors. <h3>Conclusion</h3> Non-radiographic clinical parameters do not adequately identify rheumatoid arthritis patients with radiographically progressive joint disease. Performing routine x-rays to target new RA treatments that stabilise radiologic joint disease toward radiologic progressors is likely to yield the most favourable cost-effectiveness ratios.
Dual Antiangiogenesis Agents Bevacizumab Plus Trebananib, without Chemotherapy, in First-line Treatment of Metastatic Colorectal Cancer: Results of a Phase II Study
Authors: Jennifer Mooi, Fiona Chionh, Peter Savas, Jessica Da Gama Duarte, Geoffrey Chong, Stephen Brown, Rachel Wong, Timothy J. Price, Alysson Wann, Effie Skrinos, John M. Mariadason, Niall C. Tebbutt
Journal: Clinical Cancer Research (2021)

To assess the efficacy and safety of dual antiangiogenesis agents, bevacizumab plus trebananib, without chemotherapy, in first-line treatment of metastatic colorectal cancer (mCRC).This open-label phase II study enrolled patients with unresectable mCRC with no prior systemic treatment. All patients received bevacizumab 7.5 mg/kg 3-weekly and trebananib 15 mg/kg weekly. The primary endpoint was disease control [stable disease, partial response (PR), or complete response (CR)] at 6 months (DC6m). Secondary endpoints included toxicity, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Exploratory biomarkers in plasma angiogenesis-related proteins, tumor gene expression, and plasma antibodies to tumor antigens were examined.Forty-five patients were enrolled from four Australian sites. DC6m was 63% [95% confidence interval (CI), 47-77]. ORR was 17% (95% CI, 7-32), comprising of seven PRs. Median duration of response was 20 months (range, 10-48 months). Median PFS was 8.4 months and median OS 31.4 months. Grade 1-2 peripheral edema and joint-related symptoms were common. Overall incidence of grade 3-4 adverse events (AE) of any type was 33% (n = 15). Expected AEs of bevacizumab treatment did not appear to be increased by the addition of trebananib.In a first-line mCRC population, the dual antiangiogenic combination, bevacizumab plus trebananib, without chemotherapy, was efficacious with durable responses. The toxicity profile of the combination was manageable and did not exceed that expected with bevacizumab +/- chemotherapy. Exploratory biomarker results raise the hypothesis that the antiangiogenic combination may enable the antitumor immune response in immunotolerant colorectal cancer.
Microglial activation elicits a negative affective state through prostaglandin-mediated modulation of striatal neurons
Authors: Anna M. Klawonn, Michael Fritz, Silvia Castany, Marco Pignatelli, Carla Canal, Fredrik Similä, Hugo A. Tejeda, Julia Levinsson, Maarit Jaarola, Johan Jakobsson, Juan Hidalgo, Markus Heilig, Antonello Bonci, David Engblom
Journal: Immunity (2021)
Imagery Rescripting and Imaginal Exposure in Nightmare Disorder Compared to Positive Imagery: A Randomized Controlled Trial
Authors: Carolin Schmid, Kathrin Hansen, Tana Kröner-Borowik, Regina Steil
Journal: Psychotherapy and Psychosomatics (2021)

Both imagery rescripting and imaginal exposure have been proven to be effective in the treatment of chronic nightmares when compared to a waitlist condition. Little is known about their comparative efficacy and their efficacy compared to an active control.The aims of this study were to compare the two treatments to one another and to positive imagery as an active control, and to explore covariates of the treatment effect.In this single-blinded randomized controlled trial, 96 patients with nightmare disorder (idiopathic nightmares) from an outpatient clinic were randomly assigned to a single individual treatment session of rescripting, exposure, or positive imagery and 4 weeks of practice at home. The primary outcome was nightmare distress, and the secondary outcomes were nightmare frequency, nightmare effects, self-efficacy, and general psychopathology.Nightmare distress was reduced in all groups (imagery rescripting: Cohen's d = -1.04, imaginal exposure: d = -0.68, positive imagery: d = -0.57), as were nightmare frequency, nightmare effects, and psychopathology. Self-efficacy was enhanced. No differential treatment effects were found on any primary or secondary measure. Treatment gains were not associated with demographic or disorder characteristics, baseline values, treatment credibility, or the number of practice sessions.Even short nightmare treatments are effective regardless of personal characteristics, and different interventions produce similar results. Future research should aim to clarify the mechanisms of action. Health care should make more use of these powerful and easy-to-administer nightmare treatments.
Pathergy in Neutrophilic Dermatosis
Authors: Ji-Hyun Moon, Julie Huynh
Journal: New England Journal of Medicine (2021)

A 7-year-old girl presented with fever and painful blisters on her arms, legs, and face. On hospital day 5, a new skin ulcer developed at an intravenous cannula site. Biopsy results were consistent with a neutrophilic dermatosis.
A Comprehensive Approach to Increase Adult Tobacco Cessation
Authors: Brenna VanFrank, Letitia Presley-Cantrell
Journal: JAMA (2021)

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