tbuckley/cabot-search huggingface dataset:
First-in-human phase I study of HPN424, a tri-specific half-life extended PSMA-targeting T-cell engager in patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Johanna C. Bendell, Lawrence Fong, Mark N. Stein, Tomasz M. Beer, Ashley Ross, Xin Gao, Aaron Weitzman, Richard Austin, Vaishnavi Ganti, Che-Leung Law, Bryan Lemon, Holger Wesche, Johann S. De Bono
Journal: Journal of Clinical Oncology (2020)

5552 Background: HPN424 is a first-in-class, prostate-specific membrane antigen (PSMA)-targeting T-cell engager designed as a small, globular protein to enable efficient solid-tumor penetration with prolonged half-life. HPN424 is derived from the TriTAC platform (Tri-specific T-Cell-Activating Construct) and engineered with three binding domains: anti-PSMA for tumor cell engagement, anti-albumin for half-life extension and anti-CD3 for T-cell engagement. Methods: This Ph I study is evaluating HPN424 in progressing mCRPC patients (pts) who have received &gt;2 prior systemic therapies. Primary endpoints are safety, tolerability and determination of MTD/RP2D. Secondary objectives are pharmacokinetics (PK), pharmacodynamics, immunogenicity, and preliminary anti-tumor activity. HPN424 is administered IV once weekly. Tumor assessments include PSA, CT, and bone scans every 9 weeks. Results: As of 1/17/20, 27 pts were dosed in 8 cohorts ranging from 1.3 to 72ng/kg. Pts received a median of 6 prior systemic regimens, including &gt;1 novel AR therapy, and 59% received prior chemotherapy for mCRPC. Median PSA at baseline was 251 ng/mL (range: 0.05 – 5000). No DLTs have been observed. The most common grade &gt;3 TRAEs were cytokine release syndrome (CRS) (3 pts) and transient elevated liver transaminases (2 pts) that occurred concurrently with CRS. All CRS events resolved and pts were successfully re-treated. Short-term steroid premedication was effective in limiting CRS and allowing long-term weekly treatment. HPN424 demonstrated dose proportional increase in Cmax and AUC with a geometric mean T1/2 of 30.5 hours. Dose-dependent, transient increases in peripheral cytokine and chemokine levels were observed. Reduction in circulating tumor cells (CTCs) was seen in 11 of 19 pts with measurable CTC at baseline. Six pts had PSA decreases from baseline ranging from -3.8% to -76%, including 2 pts with PSA decline ≥50%. Ten of 20 pts (50%) with &gt; 18 weeks follow-up remained on study beyond week 18 and includes 8 pts on study &gt; 24 weeks. Conclusions: HPN424 represents a novel half-life extended PSMA-targeting T-cell engager that can be safely administered once weekly. AEs have been transient and manageable. Cytokine increases indicate T-cell activation. CTC reductions in subset of pts suggest target engagement. Early signs of clinical activity include PSA reductions and time on study, including 8 pts on study &gt; 24 weeks. Dose escalation is ongoing, including exploration of step dosing. Clinical trial information: NCT03577028 .
Call for premarital physical check-up from families and society
Authors: 吴虹桥
Journal: BMJ (2006)

自2003年执行国务院 第5条结婚可无婚检证明以来,全国婚前医学检查(婚检)率由2002年的69%[1]减少到2003年的53%[2]和2004年的1%～10%.河南省1996～2002年婚检率为40.50%,2004年仅为0.68%,2年少检出患者39 432人,其中传染病9 425人,性病1 783人,不宜生育者689人,限制生育性别者152人[2].2004年福建省因未行婚检,可能漏掉的指定传染病人数为8 517人,其中性病人数为4 429人[3].广东省珠海市2004年的婚检率为6.2%,其中梅毒的检出率2003年为0.3%,2004年无检出[4].广东省中山市2003年婚检率为100%,疾病检出率为7.8%,2003年10月1日后的1年零6个月,婚检率为3.4%,疾病检出率为1.3%,出生缺陷发生率由81.40/万～132.48/万上升至149.36/万～170.76/万,胎传梅毒发生率由3.72/万上升至23.84/万[5]。
Impact of cetuximab sequence on progress-free survival (PFS) and overall survival (OS) in patients with RAS wild-type metastatic colorectal cancer (mCRC): A real-world study.
Authors: Qirong Geng, Wenxiu Cheng, Zhiyu Chen, Wen Zhang, Xiaodong Zhu, Weijian Guo
Journal: Journal of Clinical Oncology (2020)

e16042 Background: Cetuximab provides a clear clinical benefit in the treatment in patients with RAS wild-type mCRC irrespective of treatment line, but the best sequence is still under investigation. Methods: Patients with RAS wild-type mCRC (2011-2019) who received cetuximab therapy were retrospectively analyzed. They were stratified based on the cetuximab treatment sequence, into the 1 st , 2 nd , 3 rd or later-lines groups. The primary objective was to investigate the impact on Cetuximab sequence (2 nd vs. 3 rd and later-line) in PFS and OS. As for patients received the 3 rd or later-line cetuximab with irinotecan therapy after refractory to the prior 1 st and 2 nd -line combined chemotherapy with fluoropyrimidine, oxaliplatin, and irinotecan, they will get another PFS of 2 nd -line chemotherapy (PFSchemo) besides the PFS of 3 rd or later-line cetuximab compared with the cetuximab 2 nd -line used patients. We combined the PFSchemo to the PFS of 3 rd or later-line cetuximab, then compared with PFS of 2 nd -line cetuximab to evaluate the primary objective in PFS. As for the OS of primary objective, we calculated it from start of the 2 nd -line of treatment. The secondary objective was to compare the efficacy of cetuximab sequence (1 st vs. 2 nd and later-lines) in OS calculated from start of the 1 st -line of treatment. Results: In total, 193 patients were included: 106 in the 1 st , 41 in the 2 nd , and 46 in the 3 rd -line groups. No difference was observed in baseline characteristics as sex,age,site of primary tumour,number of metastatic sites in the three groups. The median PFS of the 2 nd -line and 3 rd or later-line groups were 7.1 (95% CI 6.39-7.80) and 13.87 months(95% CI 11.44-16.29) respectively. PFS of the 3 rd or later-line group was significantly longer than that of the 2 nd -line group (hazard ratio[HR], 0.552; 95% CI, 0.349 to 0.871; P = 0.01). Median OS was 17.8 months (95% CI 13.5-22.1) in the 2 nd -line and 27.4 months (95% CI 20.69-34.16) in the 3 rd or later-line group (HR, 0.597; 95% CI 0.341 to 1.043; P = 0.07) from start of 2 nd -line therapy. The median OS was 28.17 months (95% CI 22.11-34.22) in the 1 st -line group and 33.10 months (95% CI 26.88-39.31) in the 2 nd and later-lines group (HR, 0.724; 95% CI 0.507 to 1.304; P = 0.075) calculated from the 1 st -line of therapy. Conclusions: In a real-world cohort we found that later-line especially 3rd or later-line therapy of cetuximab, may be more benefit for patients with RAS wild type mCRC, as 3 rd or later-line use of cetuximab give one more line therapy chance.
Follow up of patients after percutaneous coronary intervention in community
Authors: Lan Ni, Jinhua Xue
Journal: BMJ (2017)

Objective
To follow up patients after percutaneous coronary intervention (PCI) in the community.


Methods
One hundred and eleven patients in Hudong community of Shanghai Pudong New Area, who underwent PCI from august 2014 to august 2016 were followed up. During the follow-up the gender, age, smoking history, drinking history, body mass index (BMI), main concomitant disease, drug treatment and health education were surveyed by face to face interview.


Results
There were 63 males and 48 females with an average age of 67.1±10.7 years; 51.4%(57/111) patients were overweighted , 9.0%(10/111)were obese; 29.7%(33/111)had family history of early- onset ischemic cardiovascular disease; 60.3%(67/111)patients used aspirin , 36.4%(16/44)patients with aspirin intolerance used clopidogre or tigriello replaced. Drug-coated stents were implanted in 104 patients, 33.7%(35/104)withdrew dual antiplatelet drugs in less than one year; 71.1% (79/111)patients used statins and 60.1% (48/79) of them LDL-C reached the standard. Sixty seven patients had myocardial infarction or coronary heart disease with heart failure, 49.3% (33/67) of whom treated with angiotensin converting enzyme inhibitors (ACEI) / angiotensin receptor blockers (ARB). Ninety five patients had acute coronary syndromes or coronary heart disease with heart failure, 43.2% (41/95) of whom used beta-blockers. Fifty five patients(45.9%)had hypertension, and the blood pressure was controlled successfully in 54.9%(28/51)of them. Fifty five patients(49.5%)had diabetes mellitus and the glycosylated hemoglobin(HbA1c)was <7% in 27.3%(15/55)of them. Seventeen patients (15.3%) received weight management guidance, 50.5%(56/111)) patients received guidance on proper diet, 50.5% (56/111) received guidance on medication and precautions, 80.1%(90/111)patients received guidance on when to call emergency calls.


Conclusions
The follow-up analysis shows that the compliance rate of anticoagulation and lowering LDL-C drug use is low, and the treatment of concomitant diseases and health education are not satisfactory for patients after PCI in the community.


Key words: 
Angioplasty, transluminal, percutaneous coronary; Treatment; Community health centers; General practitioners
Clinical efficacy of combined Baixuan Xiatare Capsules for Psoriasis Vulgaris
Authors: Chunsheng Yang, Yushu Zhang, Li Yuan, Ping Liu
Journal: BMJ (2014)

All 114 patients with psoriasis punctata (A group) and another 172 with psoriasis plaque (B group) from May 2007 to October 2012 were divided into two groups respectively. They were further divided into test A (n=60) and control A (n=54); test B (n=90) and control B (n=82). The test group received Baixuan Xiatare Capsules combined with narrow-band ultraviolet B phototherapy and orsalin ointment and the control group with narrow-band ultraviolet B phototherapy and orsalin ointment. The efficacy was evaluated by psoriasis area and severity index (PASI) at pre-treatment versus 8 weeks. The total effective rate was 96.7% in test A group versus 81.5% after treatment in control A group (χ2=6.958, P<0.05). And the total effective rate was 86.7% in test B group versus 71.9% in control B group(χ2=5.732, P<0.05).


Key words: 
Psoriasis; Treatment outcome
Assessing the utility of monitoring IgA multiple myeloma patients with quantitative serum IgA levels.
Authors: Alissa Visram, Abdullah S. Al Saleh, Harsh V Parmar, David L Murray, David Dingli, Martha Lacy, Angela Dispenzieri, Morie A. Gertz, Francis Buadi, Prashant Kapoor, Suzanne R. Hayman, Rahma M. Warsame, Taxiarchis Kourelis, Mustaqeem Ahmad Siddiqui, Wilson I. Gonsalves, Eli Muchtar, John Anthony Lust, S. Vincent Rajkumar, Shaji Kumar
Journal: Journal of Clinical Oncology (2020)

e20515 Background: IgA monoclonal proteins (MCPs), unlike IgG MCPs, often migrate in the beta region on serum protein electrophoresis (SPEP) which can lead to underestimation of their size due to the co-migration with physiologic proteins. In IgA multiple myeloma (MM), the utility of quantitative IgA levels in assessing disease response in comparison to SPEP is not well studied. Methods: We retrospectively analyzed 304 IgA MM patients, diagnosed between 2004 and 2018, with available serial MCP and quantitative IgA levels. Kaplan Meier analysis was used to estimate the median progression free survival (mPFS) using the IMWG criteria and our study definition of IgA progression (2 consecutive IgA values that are &gt; 25% above the nadir IgA value and above upper limit of normal (ULN) of 356 mg/dL, and a detectable IgA MCP on serum immunofixation). The mPFS was defined as the time from treatment initiation until disease progression or death. Results: IgA MCP migrated in the beta region in 134 (44%) patients, and in the gamma region in 150 (56%) patients. At diagnosis the median MCP was 3 (IQR 1.9-4) g/dL and the median IgA was 3240 (IQR 2008-4420) mg/dL. The median time from treatment initiation to MCP nadir was 80 (IQR 42-144) days and median time to IgA nadir was 154 (IQR 90-238) days. At MCP nadir 40% of patients had an IgA above the ULN. All complete responders (n = 104) had normal IgA levels, with a median IgA of 54 (IQR 27-88) g/dL. A ≥90% decrease in IgA between treatment initiation and IgA nadir, compared to a &lt; 90% decrease, was associated with a longer mPFS (34 vs. 20 months, p = 0.006) and overall survival (97 vs. 33 months, p = 0.003). Patients with serial MCP and IgA levels available prior to progression (n = 195) were used to compare the mPFS using the IMWG and IgA progression criteria. The mPFS using the IgA criteria was 32 (95% CI 29-39) months, versus 39 (95% CI 33-45) months using IMWG criteria. Overall, 92 (47%) patients progressed by both IMWG and IgA criteria. At the time of progression using the IgA criteria compared to at IMWG progression, the median hemoglobin was higher (13.3 vs. 11.6 g/dL, respectively, p &lt; 0.001) and fewer patients had new symptomatic bone lesions (2% vs. 33%, respectively, p &lt; 0.001). Conclusions: In IgA MM patients, monitoring quantitative IgA levels predicts disease response and allows for earlier detection of disease progression, prior to the development of end organ damage.
Safety and efficacy of biweekly gemcitabine in combination with capecitabine (GemCap) in elderly and frail patients (pts) with resected pancreatic cancer (PC).
Authors: Nausheen Hakim, Jeffrey Chi, Hasan Rehman, William Nealon, Gary B Deutsch, Elliot Newman, Sandeep Anantha, Gene Coppa, Danielle Deperalta, Arvind Rishi, Antonia Maloney, Linda Moriarty, Melissa H Smith, Jyothi Jose, Wasif M. Saif
Journal: Journal of Clinical Oncology (2020)

4628 Background: ESPAC-4 study showed that GemCap conferred a survival benefit over gemcitabine monotherapy in resected PC patients. ESPAC-4 included patients with median age of 65 years (37-81) and ECOG performance status (PS) of 0 (43%), 1 (54%) and 2 (2%) who received a median cumulative dose of gemcitabine of 15,000 mg/m2, capecitabine. Here we present our experience with an adopted biweekly regimen of GemCap in patients who were ≥ 75 years and those who were deemed not suitable for ESPAC-4 regimen. Methods: Patients ≥ 75 years with resected PC, ECOG PS of 0-2 and no prior treatments were included. Patients were treated with a modified regimen of gemcitabine (1000-2000 mg/m2) every 2 weeks and capecitabine (800-1000 mg/m2) day 1-7 every 2 weeks. Patients were evaluated for progression-free survival (PFS), overall survival (OS) and sites of recurrence. Toxicities were graded according to NCI CTCAE v5.0. Results: Thirty-five (22M, 13F) patients, ≥ 75 (median age 79) treated with biweekly Gem-Cap adjuvant treatment. 7 (28%) patients had ECOG PS of 1 and 28 (72%) had ECOG PS of 2. There were 5, 7 and 16 patients with stage I, II and III disease. Nine patients (25%) had R1 and 26 (75%) had R0 resection. The median PFS and OS were 8.0 months and 22.0 months. Nine (25%) had local recurrence, 21 (60%) had metastatic disease and 3 (8.6%) had NED. Two patients were lost to follow-up. The most frequent toxicities were grades 1-2 anemia (20%), thrombocytopenia (8%) and hand-foot syndrome (HFS) (10%). Grade ≥3 included diarrhea (4%) and HFS (1%) with no treatment-related discontinuations. Treatment compliance was 100%. Delays were necessary in 7% of cases and dose reduction was required in 4% of cases. There was no treatment related death. Conclusions: This schedule of biweekly GemCap regimen suggests an acceptable option in for elderly, frail patients with PC and warrants further exploration in patients not suitable for FOLFIRINOX, full dose GemCap or a clinical trial. This regimen required fewer dose reduction, omission or delays and allowed to administer pegylated-filgrastim. Previous studies have also shown decreased toxicity and equal efficacy of 7/7 schedule of capecitabine. Moreover, fewer visits to oncology and related expense do favor towards benefit. Additionally, this tolerable regimen is ideal to be combined with immunotherapy in clinical trials for this patient population.
A multicenter phase 1 study of nivolumab for relapsed hematologic malignancies after allogeneic transplantation
Authors: Matthew S. Davids, Haesook T. Kim, Caitlin Costello, Alex F. Herrera, Frederick L. Locke, Rodrigo O. Maegawa, Alexandra Savell, Michael Mazzeo, Adrienne Anderson, Alexander P. Boardman, Augustine Weber, David Avigan, Yi-Bin Chen, Sarah Nikiforow, Vincent T. Ho, Corey Cutler, Edwin P. Alyea, Pavan Bachireddy, Catherine J. Wu, Jerome Ritz, Howard Streicher, Edward D. Ball, Asad Bashey, Robert J. Soiffer, Philippe Armand
Journal: Blood (2020)
Review: some computerised cognitive-behavioural therapies are effective for treating mild-to-moderate depression
Authors: Kaltenthaler, Parry, Beverley, 丰雷, 陈玉辉, 赵茜, 张华
Journal: BMJ (2009)

纳入的研究均比较了认知行为疗法（cognitive—behaviouraltherapy，CBT），单独或者配合带有电脑界面或电脑应答电话的软件包一起使用，以及常用治疗——包括治疗师指导的CBT，咨询，药物治疗和其他CBT（例如，阅读治疗或者CBT小组治疗），对伴或不伴焦虑的轻-中度抑郁患者的疗效。除外针对产后抑郁，双相障碍，伴有精神病性症状的抑郁，目前为重度抑郁或者存在严重自杀观念的患者的研究。结局包括精神症状（抑郁）的改善。
Risk factors of cervical intraepithelial neoplasia
Authors: 耿筱虹, 刘奕, 邹长林, 金菲, 吕杰强
Journal: BMJ (2007)

目的 探讨与宫颈上皮内瘤变(CIN)发生有关的危险因素.方法 回顾性研究2002年至2005年温州医学院附属第二医院妇科门诊患者中组织病理学诊断为CIN的108例病例资料,应用单因素和多因素非条件logistic回归分析.结果 单因素非条件logistic回归分析显示,宫颈人乳头瘤病毒(HPV)感染是发生CIN的最强危险因素(OR=9.020),其余依次为性伴数(OR=1.644)、教育程度(OR=1.585)、性伴的多性伴(OR=1.456),性防护(OR=0.235)是CIN的保护因素;多因素非条件logistic回归分析显示,宫颈HPV感染、性伴数、教育程度及性防护进入方程.结论 CIN的发生、发展与宫颈HPV感染、性伴数、教育程度及性防护等因素相关.因此应加强对宫颈HPV感染的认识与管理,加强人群的卫生宣教,预防性传播疾病。
Prognostic role of macrophage infiltration and monocyte-to-lymphocyte ratio in stage III colon cancer: The MIRROR study.
Authors: Debora Basile, Maurizio Polano, Silvia Buriolla, Claire Gallois, Francesco Cortiula, Carla Corvaja, Marco de Scordilli, Anna Michelotti, Annamaria Parnofiello, Lorenzo Gerratana, Elena Ongaro, Eva Andreuzzi, Giuseppe Toffoli, Angela Buonadonna, Maurizio Mongiat, Aziz Zaanan, Giuseppe Aprile, Vincenzo Canzonieri, Julien Taieb, Fabio Puglisi
Journal: Journal of Clinical Oncology (2020)

e16118 Background: Changes in peripheral blood cells composition may reflect immune microenvironment and its role in cancer growth. High monocyte-to-lymphocyte ratio (MLR) could be a marker of tumor’s recruitment of suppressive cells, showing a prognostic role. This study aimed to assess the prognostic impact of macrophage infiltration and MLR in stage III colon cancer (CC) patients (pts). Methods: This multicentric study retrospectively analyzed a consecutive cohort of 423 CC pts treated between 2008-2019 at the Cancer Centre of Aviano (Italy) (n = 300) and at the European Georges Pompidou Hospital of Paris (France) (n = 123). The association of MLR with disease-free survival (DFS) and overall survival (OS) was evaluated with Cox regression analyses. Random Forrest was implemented on python using h2oai. Performance was assessed in terms of accuracy (ACC) and Matthews Coefficient (MCC). Analyses was adjusted on classical prognostic factors of stage III CC such as pT, pN, grade, location, ECOG PS. Results: Overall, 77% had pT1-3, 30% pN2 and 73% G1-2 tumors. Interestingly, 25% had a lymphatic and vascular invasion, 42/230 (18%) had MSI status, 69/152(45%) and 19/114 (13%) were KRAS and BRAF mutant. 56% had CEA &gt; 5. Pts were treated with fluoropyrimidine and oxaliplatin as adjuvant therapy. Notably, 130 cases were analyzed according to lymphocytic and macrophage infiltration (CD163, CD68, CD3, CD8). Of them, 78% had a CD163/CD8 ratio ≤3 and 74% a CD8/CD3 ratio ≤1.5. At median follow-up of 57 months, median DFS and OS were not reached, 31% of pts relapsed and 23% dead. By multivariate analysis, including statistically significant prognostic variables, CD163/CD8 ratio (HR 1.15, p = 0.039, 95%C.I. 1.1-1.32) and MLR &gt; 0.45 (HR 2.98, p = 0.008, 95%C.I. 1.33-6.67) were associated with worse DFS. By multivariate analysis for OS, including statistically significant confounding variables, MLR &gt; 0.45 (HR4.32, P = 0.012, 95%C.I. 1.37-9) and BRAF mutation predicted worse OS. According random survival forest for OS, CD68/CD3 were the first variable of importance (0.06), followed by MLR (0.009) and CD8 (0.007). Interestingly, high MLR followed by CEA, MSI, KRAS were the features linked with organotropism on liver (ACC 0.6 ±0.3), while high MLR, KRAS, pN, pT were mainly linked with lung colonization (ACC 0.6 ±0.2). Conclusions: High pre-treatment levels of MLR and CD163/CD8 ratio in stage III CC are independently associated with worse prognosis. The present study paves the way to a prospective validation of these promising cost-effective biomarkers.
NKTR-214 immunotherapy synergizes with radiotherapy to stimulate systemic CD8<sup>+</sup>T cell responses capable of curing multi-focal cancer
Authors: Joshua M Walker, Annah S Rolig, Deborah H Charych, Ute Hoch, Melissa J Kasiewicz, Daniel C Rose, Michael J McNamara, Ian F Hilgart-Martiszus, William L Redmond
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background High-dose radiotherapy (RT) is known to be immunogenic, but is rarely capable of driving clinically relevant abscopal antitumor immunity as monotherapy. RT is known to increase antigen presentation, type I/II interferon responses, and immune cell trafficking to irradiated tumors. Bempegaldesleukin (NKTR-214) is a CD122-preferential interleukin 2 (IL-2) pathway agonist that has been shown to increase tumor-infiltrating lymphocytes, T cell clonality, and increase PD-1 expression. NKTR-214 has increased drug half-life, decreased toxicity, and increased CD8 + T cell and natural killer cell stimulation compared with IL-2. Methods Animals bearing bilateral subcutaneous MCA-205 fibrosarcoma or CT26 colorectal tumors were treated with NKTR-214, RT, or combination therapy, and tumor growth of irradiated and abscopal lesions was assessed. Focal RT was delivered using a small animal radiation research platform. Peripheral and tumor-infiltrating immune phenotype and functional analyses were performed by flow cytometry. RNA expression profiling from both irradiated and abscopal lesions was performed using microarray. Results We demonstrate synergy between RT of a single tumor and NKTR-214 systemic therapy resulting in dramatically increased cure rates of mice bearing bilateral tumors compared with RT or NKTR-214 therapy alone. Combination therapy resulted in increased magnitude and effector function of tumor-specific CD8 + T cell responses and increased trafficking of these T cells to both irradiated and distant, unirradiated, tumors. Conclusions Given the increasing role of hypofractionated and stereotactic body RT as standard of care treatments in the management of locally advanced and metastatic cancer, these data have important implications for future clinical trial development. The combination of RT and NKTR-214 therapy potently stimulates systemic antitumor immunity and should be evaluated for the treatment of patients with locally advanced and metastatic solid tumors.