tbuckley/cabot-search huggingface dataset:
Impact of rheumatoid arthritis on major cardiovascular events in patients with and without coronary artery disease
Authors: Brian Bridal Løgstrup, Kevin Kris Warnakula Olesen, Dzenan Masic, Christine Gyldenkerne, Pernille Gro Thrane, Torkell Ellingsen, Hans Erik Bøtker, Michael Maeng
Journal: Annals of the Rheumatic Diseases (2020)

Introduction Rheumatoid arthritis (RA) is a risk factor for cardiovascular disease. The clinical consequences of coincident RA and coronary artery disease (CAD) are unknown. Objective We aimed to estimate the impact of RA on the risk of adverse cardiovascular events in patients with and without CAD. Methods A population-based cohort of patients registered in the Western Denmark Heart Registry, who underwent coronary angiography (CAG) between 2003 and 2016, was stratified according to the presence of RA and CAD. Endpoints were myocardial infarction (MI), major adverse cardiovascular events (MACE; MI, ischaemic stroke and cardiac death) and all-cause mortality. Results A total of 125 331 patients were included (RA: n=1732). Median follow-up was 5.2 years. Using patients with neither RA nor CAD as reference (cumulative MI incidence 2.7%), the 10-year risk of MI was increased for patients with RA alone (3.8%; adjusted incidence rate ratio (IRR adj ) 1.63, 95% CI 1.04 to 2.54), for patients with CAD alone (9.9%; IRR adj 3.35, 95% CI 3.10 to 3.62), and highest for patients with both RA and CAD (12.2%; IRR adj 4.53, 95% CI 3.66 to 5.59). Similar associations were observed for MACE an all-cause mortality. Conclusions In patients undergoing CAG, RA is significantly associated with the 10-year risk of MI, MACE and all-cause mortality regardless of the presence of CAD. However, patients with RA and CAD carry the largest risk, while the additive risk of RA in patients without CAD is minor. Among patients with RA, risk stratification by presence or absence of documented CAD may allow for screening and personalised treatment strategies
Diagnosis and treatment of corpus cavernosum penis rupture
Authors: Le Che
Journal: BMJ (2010)

The clinical data of 16 patients with rupture of corpus cavernosum penis were retrospectively reviewed.The patients were referred to the Department of Urology from January 2005 to November 2009.The causes of penile injury were trauma due to sexual intercourse ( 12 cases), trauma due to masturbatory (2 cases), traffic accidents ( 1 case) and others ( l case).All patients received immediate surgical treatment; 14 out of 16 patients were followed up for a mean period of 3 months.Sexual function was recovered with satisfactory erection in 11 patients, 3 patients complained pain or uncomfortab]eness during erection.Sexual trauma was the main cause of penile fracture.Immediate intervention for penile fracture can achieve satisfactory early and late results.

Key words: 
Penile diseases;  Wounds and injuries
Phase I monotherapy dose escalation of RGX-202, a first-in-class oral inhibitor of the SLC6a8/CKB pathway, in patients with advanced gastrointestinal (GI) solid tumors.
Authors: Johanna C. Bendell, James Fredric Strauss, Marwan Fakih, Autumn Jackson McRee, Andrew Eugene Hendifar, Lee S. Rosen, Andrea Cercek, Eric Keith Rowinsky, Michael Szarek, Foster Gonsalves, Isabel Kurth, Celia Andreu, Robert Busby, Scott Spector, David Martin Darst, Masoud Tavazoie, Syed Raza, Narayan Lebaka, Robert Wasserman, Yelena Yuriy Janjigian
Journal: Journal of Clinical Oncology (2020)

3504 Background: About 65% of advanced colorectal cancer (CRC) patients (pts) have creatine kinase B (CKB) expressing tumors. CKB expressing (CKB+) GI cancer cells import creatine via the creatine transporter SLC6a8 and utilize it to generate intracellular ATP. RGX-202, a small molecule inhibitor of SLC6a8, reduces intracellular creatine and ATP levels, leading to apoptosis. RGX-202 treatment triggers complete tumor regressions in multiple CKB+ preclinical models, including KRAS mutant CRC. Methods: RGX-202-001 is a phase I escalation/expansion study of RGX-202 +/- FOLFIRI in pts with advanced GI tumors. The primary safety objective during dose escalation is to identify the maximum tolerated dose (MTD), or the maximum tested dose at which multiple dose-limiting toxicities (DLTs) are not observed. The primary efficacy objective is to estimate the antitumor activity of RGX-202 by RECIST. Results: As of January 31, 2020, 17 pts have been treated in 4 single agent dose escalation cohorts: 600 mg BID (3 pts), 1200 mg BID (4 pts), 2400mg BID (5 pts) and 3600mg BID (5pts) given continuously. No DLTs were observed and an MTD was not reached. Treatment-related adverse events (TRAEs) occurring in &gt; 2 pts are shown in the Table. There were no Grade 4 TRAEs. At the highest dose, 2 of 3 CRC pts had prolonged disease control: a patient with a KRAS G13D mutant cancer had SD for 14 weeks; and a patient with KRAS G12V mutant (MSS) cancer had a confirmed PR ongoing at 30 weeks. Exposure to RGX-202 was greater than dose-proportional and the average AUC 0-24 ranged from ~15,700 ng-hr/mL in cohort 1 to 241,097 ng-hr/mL in in Cohort 4. Serum and urine creatine levels, pharmacodynamic markers of SLC6a8 inhibition, correlated with systemic exposure to RGX-202. Conclusions: Among 17 patients treated with single agent therapy, no DLTs occurred; notably, exposures predicted to be sufficient to inhibit human tumor growth from preclinical models were achieved along with concomitant pharmacodynamic effects. These data, along with a durable PR observed in the highest dose cohort, support further development of RGX-202. Consequently, dose escalation in combination with FOLFIRI in patients with advanced GI cancers is underway with plans for expansion in CKB+ CRC pts. Clinical trial information: NCT03597581 . [Table: see text]
Gemcitabine with carboplatin in metastatic breast cancer: Characterizing outcomes in a modern, real-world population.
Authors: Jordyn Paige Higgins, Chloe Lalonde, Kristina F. Byers, Christine Davis, Kandra Horne, Subir Goyal, Zhengjia Chen, Jane Lowe Meisel, Joan L. Kramer, Meagan Spencer Barbee
Journal: Journal of Clinical Oncology (2020)

e13085 Background: The specifics of the salvage regimen gemcitabine/carboplatin (G/C) in metastatic breast cancer (MBC) are not well-characterized and are limited to the clinical trial setting, which often excludes heavily pretreated patients with high disease burden and velocity. The primary objective of this study is to assess real-world outcomes in patients with MBC treated with G/C. Methods: A retrospective chart review was conducted on adults with MBC who received &gt;1 dose of G/C at Emory Healthcare / Winship Cancer Institute from December 1, 2005 to April 30, 2019 (n = 109). Patients were stratified by receptor status (hormone receptor (HR), triple-negative (TN), and human epidermal growth factor receptor-2 (HER2)). Results: Patients were heavily pretreated (median 2 lines, range 0-11) and had extensive metastatic disease (median 3 sites, range 1-6). The median starting doses were carboplatin AUC 2 (range: 1.5-5) and gemcitabine 1000 mg/m 2 (range 400-1100). The median cycle length was 21 days (range 14-28). The median progression-free survival (mPFS) was 3.7 months and median overall survival (mOS) was 7.7 months. OS at 24 months was 23.1%. Previous immunotherapy, radiation for palliation, or historical receipt of neoadjuvant/adjuvant cytotoxic therapy was significantly associated with improved survival outcomes, while possessing lung, liver, or bone metastases was significantly associated with worse survival outcomes. The presence of brain metastases did not correlate with outcomes. Side effect/intolerance led to dosing and scheduling adjustments in 38.5% and 49.5% of patients, respectively, and resulted in treatment discontinuation in 21% of patients. Hospitalization occurred in 51.4% of patients on treatment. Conclusions: G/C is a safe and effective regimen in real-world MBC patients regardless of receptor subtype. Even low doses of G/C may provide some CNS penetration and control. Improved survival outcomes associated with previous immunotherapy and radiation for palliation may be due to disease control or carry over effect and warrant further study. [Table: see text]
Splice of Life for Cancer: Missplicing of PPP2R5A by Mutant SF3B1 Leads to MYC Stabilization and Tumorigenesis
Authors: Caitlin M. O'Connor, Goutham Narla
Journal: Cancer Discovery (2020)

Abstract Summary: Although mutations in SF3B1 are the most common RNA-splicing factor mutations in cancer, determining the downstream missplicing events that drive tumorigenesis has remained challenging. Liu and colleagues present a model by which mutant SF3B1 tumors displayed high levels of oncogenic MYC activity through the missplicing of PP2A-B56α, a key post-translational regulator of MYC stability, providing a new therapeutic target and driver of SF3B1-mediated tumorigenesis. See related article by Liu et al., p. 806.
帕金森病远期并发症的预防及处理
Authors: 马敬红, 陈彪
Journal: BMJ (2008)

帕金森病是一种常见的神经系统变性疾病.目前,左旋多巴制剂仍是治疗帕金森病最有效且应用最为广泛的药物.在用药之初,左旋多巴制剂往往都有较好的疗效,能有效地改善患者的运动症状及生存质量.但通常在用药2～5年后,大部分患者会
Tolerability of radiation with concurrent temozolomide and effect on survival in chemo-refractory CNS lymphoma.
Authors: Anna Mary Brown Laucis, Katherine Selwa, Yilun Sun, Michelle Miran Kim, Kyle Clifford Cuneo, Theodore Steven Lawrence, Daniel Richard Wahl, Yoshie Umemura, Larry Junck
Journal: Journal of Clinical Oncology (2020)

e14554 Background: There is no consensus for the treatment of central nervous system lymphoma (CNSL) refractory to first line high dose methotrexate-based chemotherapy. Whole brain radiation (WBRT) has often been used but may lead to unacceptable neurocognitive dysfunction. We examined our institutional experience with treating CNSL with radiotherapy (RT) and concurrent temozolomide (TMZ) including the resultant acute and long term toxicities. Methods: This single institution IRB approved retrospective study examined treatment, toxicity, and outcome variables in adults with primary or secondary CNS lymphoma. Inclusion criteria were brain-directed RT and development of the treatment plan at our institution. Three main RT field designs were used, including low and high dose WBRT and low dose WBRT with a focal boost to residual disease (WBRT+boost). We assessed relationships between treatment approach (RT field design and concurrent TMZ use) and clinical outcomes and toxicities using multivariable logistic regression models and Kaplan-Meier methods. Toxicity was recorded using the Common Terminology Criteria for Adverse Events version 5. Results: A total of 93 patients with median age of 57 years (range 24 – 86) treated from 2004 – 2019 were included, and 26 patients received concurrent TMZ. The RT field design of low dose WBRT (median dose: 23.4Gy) plus focal boost (median dose: 21.6Gy) was associated with favorable overall survival (OS) and progression free survival (PFS) without any significant difference in Grade 3+ toxicity compared to low dose WBRT (p = 0.20) or WBRT without boost (p = 0.80). Concurrent TMZ with RT was associated with significantly improved OS (HR 0.46, p = 0.025) and CNS PFS (HR 0.49, p = 0.019). Four of nine (44%) Grade 3+ non-hematologic toxicities occurred in patients receiving concurrent TMZ (p = 0.40). The most common non-hematologic toxicities included fatigue and nausea. Long term neurocognitive dysfunction was similar whether or not patients received concurrent TMZ (21% in TMZ group vs 23% in non-TMZ group; OR 0.87, 95% CI 0.25 – 2.68, p = 0.82) and irrespective of RT field design (WBRT+boost vs low dose WBRT p = 0.25, WBRT+boost vs WBRT without boost p = 0.19). Conclusions: Our findings suggest that concurrent TMZ use with brain RT for chemo-refractory CNSL is a promising strategy, with improved survival and no major additional toxicity. Further research that includes rigorous neurocognitive assessments is needed in prospective clinical trials to guide treatment approaches using concurrent TMZ with brain RT in CNSL patients.
NEJ026: Final overall survival analysis of bevacizumab plus erlotinib treatment for NSCLC patients harboring activating EGFR-mutations.
Authors: Makoto Maemondo, Tatsuro Fukuhara, Haruhiro Saito, Naoki Furuya, Kana Watanabe, Shunichi Sugawara, Shunichiro Iwasawa, Yoshio Tsunezuka, Ou Yamaguchi, Morihito Okada, Kouzou Yoshimori, Ichiro Nakachi, Akihiko Gemma, Koichi Azuma, Koichi Hagiwara, Toshihiro Nukiwa, Satoshi Morita, Kunihiko Kobayashi
Journal: Journal of Clinical Oncology (2020)

9506 Background: In NEJ026, a phase III trial comparing bevacizumab plus erlotinib (BE) to erlotinib monotherapy (E) for EGFR-mutated non-small-cell lung cancer (NSCLC), we demonstrated the progression-free survival (PFS) of BE was significantly superior to E (Saito et al. Lancet Oncol. 2019 May;20(5):625-635.). However overall survival analysis were immature at the cutoff date. Methods: Chemotherapy-naïve pts with advanced non-squamous NSCLC harboring EGFR-mutation were randomly assigned to receive either combination with erlotinib (150 mg daily) plus bevacizumab (15 mg/kg iv q3w) or erlotinib (150 mg daily). The primary endpoint was PFS. Secondary endpoints were OS, RR, safety, and QoL. Results: The 226 pts were assigned to BE (n=112) and E (n=114). For the follow-up OS analysis, the data cut-off date was 30 November 2019. Median follow up time was 39.2 months. Median OS was 50.7 months (95% CI, 37.3 months to not reached) with BE and 46.2 months (95% CI, 38.2 months to not reached) with E (hazard ratio, 1.00; 95% CI, 0.68 to 1.48). Twenty-nine patients (25.9%) in BE and twenty-six patients (23.2%) in E were treated by osimertinib as second line treatment. The median survival time between enrollment and progressive disease of second-line treatment (median PFS2) was 28.6 months (95% CI, 22.1 months to 35.9) with BE and 24.3 months (95% CI, 20.4 months to 29.1 months) with E (hazard ratio, 0.80; 95% CI, 0.59 to 1.10). In both arms, the median OS of patients with osimertinib second-line treatment were longer than other second-line chemotherapy groups [50.7 months (95% CI, 38.0 months to 50.7 months) vs 40.1 months (95% CI, 29.5 months to not reached), (hazard ratio, 0.645; 95% CI, 0.40 to 1.03), respectively. Conclusion: The additional effect of bevacizumab on erlotinib monotherapy for NSCLC with EGFR mutations gradually decreased in the order of PFS2 and survival, with no significant differences. Clinical trial information: UMIN000017069 .
Effect of farrerol on the proliferation of estrogen receptor-positive breast cancer by downregulating oncogenic genes with estrogen receptor response elements.
Authors: Xiao-Qing Lu, Rui Yang, Jia-Qian Zhang, Shengxiao Zhang, Huan-Hu Zhang
Journal: Journal of Clinical Oncology (2020)

e12541 Background: Breast cancer (BC) is the most common malignant tumor among women worldwide, the most common of which is estrogen receptor (ER) -positive BC. Farrerol, a noval estrogen-like chemicals, is closely associated with ER positive BC. In this study, we will explore the anticancer effect of farrerol on ER-positive BC and the detailed mechanism. Methods: Cloning formation assay and MTT assay were used to evaluate the effect of farrerol on proliferation ofcells. The affinity of farrerol, estrogen and tamoxifen with ER was tested by molecular docking technique. Point mutation was performed on the possible binding sites of ER according to the results of virtual docking, and Surface Plasmon Resonance (SPR). ER response elements in BC cells with farrerol were evaluated by qPCR. Results: With the increased farrerol concentration, the number of cell clones formed gradually decreased and the volume of clones became smaller in the ER positive McF-7 cell group, while a completely opposite clones was observed in non- ER positive MDA-MB-231 cells. The proliferation inhibition rate of McF-7 cells in the 160 mol/L and 320 mol/L groups was 45.86% and 65.3% respectively, significantly higher than that of MDA-MB-231 and normal mammary epithelial cells (P &lt; 0.05). Both molecular docking technique and SPR experiment showed that farrerol could bind to ER at different sites than estrogen binding. Fiarrerol effectively down-regulated the transcription of the oncogenes MYC and TFF1, and suppressed ER-positive BC. Conclusions: Farrerol has the opposite effect with estrogen, which inhibited the proliferation of ER-positive BC cells, and downregulated the expression of oncogenic genes with ER response elements in BC cells. Therefore, farrerol, as a natural ingredient, could be further developed and applied with its obvious inhibitory effect on ER-positive BC in the future.
Influencing factors and interventions of sexual health in female breast and gynecologic cancer survivors
Authors: Panzhen Chen, Jiwei Wang
Journal: BMJ (2018)

Female breast and gynecologic cancer affect sexual health of the survivors due to the disease itself and related treatment, resulting in sexual dysfunction and the reduced quality of life. The sexual dysfunction of patients is often overlooked, and the related interventions are less frequently mentioned. This article reviews the classification, influencing factors and interventions of sexual dysfunction in survivors of female breast cancer and gynecologic cancer, and also proposes the effective interventional strategies.


Key words: 
Genital neoplasms, female; Carcinoma; Breast neoplasms; Sexual health
Characterization and clinical course of 1000 patients with coronavirus disease 2019 in New York: retrospective case series
Authors: Michael G Argenziano, Samuel L Bruce, Cody L Slater, Jonathan R Tiao, Matthew R Baldwin, R Graham Barr, Bernard P Chang, Katherine H Chau, Justin J Choi, Nicholas Gavin, Parag Goyal, Angela M Mills, Ashmi A Patel, Marie-Laure S Romney, Monika M Safford, Neil W Schluger, Soumitra Sengupta, Magdalena E Sobieszczyk, Jason E Zucker, Paul A Asadourian, Fletcher M Bell, Rebekah Boyd, Matthew F Cohen, MacAlistair I Colquhoun, Lucy A Colville, Joseph H de Jonge, Lyle B Dershowitz, Shirin A Dey, Katherine A Eiseman, Zachary P Girvin, Daniella T Goni, Amro A Harb, Nicholas Herzik, Sarah Householder, Lara E Karaaslan, Heather Lee, Evan Lieberman, Andrew Ling, Ree Lu, Arthur Y Shou, Alexander C Sisti, Zachary E Snow, Colin P Sperring, Yuqing Xiong, Henry W Zhou, Karthik Natarajan, George Hripcsak, Ruijun Chen
Journal: BMJ (2020)

To characterize patients with coronavirus disease 2019 (covid-19) in a large New York City medical center and describe their clinical course across the emergency department, hospital wards, and intensive care units.Retrospective manual medical record review.NewYork-Presbyterian/Columbia University Irving Medical Center, a quaternary care academic medical center in New York City.The first 1000 consecutive patients with a positive result on the reverse transcriptase polymerase chain reaction assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who presented to the emergency department or were admitted to hospital between 1 March and 5 April 2020. Patient data were manually abstracted from electronic medical records.Characterization of patients, including demographics, presenting symptoms, comorbidities on presentation, hospital course, time to intubation, complications, mortality, and disposition.Of the first 1000 patients, 150 presented to the emergency department, 614 were admitted to hospital (not intensive care units), and 236 were admitted or transferred to intensive care units. The most common presenting symptoms were cough (732/1000), fever (728/1000), and dyspnea (631/1000). Patients in hospital, particularly those treated in intensive care units, often had baseline comorbidities including hypertension, diabetes, and obesity. Patients admitted to intensive care units were older, predominantly male (158/236, 66.9%), and had long lengths of stay (median 23 days, interquartile range 12-32 days); 78.0% (184/236) developed acute kidney injury and 35.2% (83/236) needed dialysis. Only 4.4% (6/136) of patients who required mechanical ventilation were first intubated more than 14 days after symptom onset. Time to intubation from symptom onset had a bimodal distribution, with modes at three to four days, and at nine days. As of 30 April, 90 patients remained in hospital and 211 had died in hospital.Patients admitted to hospital with covid-19 at this medical center faced major morbidity and mortality, with high rates of acute kidney injury and inpatient dialysis, prolonged intubations, and a bimodal distribution of time to intubation from symptom onset.
Impact of immunoparesis on clinical outcomes following bone marrow transplantation.
Authors: Nicholas Torgerson, Oluwatobi Odetola, Patrick Hagen, Nasheed Hossain, Stephanie Tsai, Scott E. Smith, Patrick J. Stiff
Journal: Journal of Clinical Oncology (2020)

e20505 Background: Immunoparesis (hypogammaglobinemia) has been shown to impact outcomes in patients with newly diagnosed multiple myeloma (MM). Its impact in the post-transplant setting and potential risk of both infections and immune dysregulation impacting relapse is less clear. We sought to assess the role of immunoparesis both pre and post autologous stem cell transplant (ASCT) in newly diagnosed MM patients. Our primary outcome was the impact of immunoparesis on progression free survival (PFS) post-ASCT controlling for maintenance therapy. Methods: We evaluated all MM patients between 2008 and 2017 at Loyola University who underwent ASCT. Inclusion criteria included first ASCT and age &gt; 18 years. We evaluated both the presence of and number of impacted immunoglobulin (Ig) classes pre-transplant and day 100, 6-months, and 12 months post-ASCT. Results: The most common MM isotype was IgG Kappa (41.01%). Immunoparesis pre-ASCT and post-ASCT at day 100, 6 months, and 12 months was seen in 75%, 89.5%, 80%, and 58.5% respectively. Median time from diagnosis to transplant was 7.75 months (5.98 – 13.73). When adjusting for pre-transplant response, conditioning regimen, and post-transplant maintenance, neither the absolute presence of or number of Ig-classes impacting was predictive of hazard of disease progression or death (OS) while ISS-stage, best response post ASCT, and time from diagnosis to transplant were (table). Conclusions: Contrary to studies in the pre-transplant setting, our analysis indicates that immunoparesis is not predictive of relapse or survival in the post-transplant setting, suggesting modification of disease process with treatment and ASCT. When controlled for maintenance therapy, immunoparesis does not increase risk of progression or decrease overall survival alleviating the concern for increased morbidity/mortality secondary to infections in the face of immunoparesis in the era of maintenance therapy. [Table: see text]