tbuckley/cabot-search huggingface dataset:
A review of 2319 domestic literatures on pulmonary embolism in recent 13 years
Authors: Chun-ping Liu, Hang-wei Chen, Wei Tian, Xuan Zhang, Nian Chen
Journal: BMJ (2008)

Objective To analyze current status of research on pulmonary embolism and changes of its knowledge in domestic academic literatures.Methods Totally,2319 domestic papers on pulmonary embolism were collected by computerized retrieval from CHKD system during the period of 1994 to 2006 with a key word ofpulmonary embolism,and were classified and summarized according to their type,contents,author's affiliation.Results Number of papers on pulmonary embolism increased quickly in recent 13 years,especially in the last five years,from 25 papers in 1994 to 430 in 2006.Most of the papers in the early stage were case reports,and the number and proportion of original articles increased obviously after 1997.Contents of the papers were mainly about clinical manifestation and examinations of pulmonary embolism,but papers on its auxiliary examinations,laboratory examinations,clinical nursing care,animal experiments,and so on were all increased.Authors of the papers were from varied departments of hospitals,mainly in the department of internal medicine,especially in the departments of cardiology and respiratory diseases,followed by the divisions of medical imaging,radiation and nuclear medicine.Papers were mainly submitted by authors from affiliated hospitals of medical schools and hospitals at city-level,and papers submitted by gross-roots hospitals such as county hospital and clinic also increased.Conclusion Significant success in diagnosis and treatment of pulmonary embolism has been achieved domestically in recent 13 years,which has been recognized popularly by Chinese physicians.

Key words: 
Pulmonary embolism;  Information retrieval; Data analysis,statistical
Multilevel Organisation of Animal Sociality
Authors: Cyril C. Grueter, Xiaoguang Qi, Dietmar Zinner, Thore Bergman, Ming Li, Zuofu Xiang, Pingfen Zhu, Andrea Bamberg Migliano, Alex Miller, Michael Krützen, Julia Fischer, Daniel I. Rubenstein, T.N.C. Vidya, Baoguo Li, Maurício Cantor, Larissa Swedell
Journal: Trends in Ecology & Evolution (2020)
Phase II study of nivolumab and salvage nivolumab + ipilimumab in treatment-naïve patients (pts) with advanced renal cell carcinoma (RCC) (HCRN GU16-260).
Authors: Michael B. Atkins, Opeyemi Jegede, Naomi B. Haas, David F. McDermott, Mehmet Asim Bilen, Charles G. Drake, Jeffrey Alan Sosman, Robert S. Alter, Elizabeth R. Plimack, Brian I. Rini, Michael E. Hurwitz, David J. Peace, Sabina Signoretti, Catherine J. Wu, Paul J. Catalano, Hans J. Hammers
Journal: Journal of Clinical Oncology (2020)

5006 Background: Nivolumab (nivo) is FDA approved for pts with VEGFR TKI-resistant RCC and the nivo + ipilimumab (nivo/ipi) combination is FDA approved for treatment naïve pts with IMDC intermediate and poor risk RCC. Little information is available on the efficacy and toxicity of nivo monotherapy in treatment naïve RCC or the efficacy of nivo/ipi salvage therapy in pts with tumors resistant to initial nivo monotherapy. Methods: Eligible pts with treatment naïve RCC received nivo 240mg IV q2 wk x 6 doses followed by 360mg IV q3 wk x 4 doses followed by 480 mg q4 wk until progressive disease (PD), toxicity, or completion of 96 wks of treatment (Part A). Pts with PD prior to or stable disease (SD) at 48 wks (pSD) were potentially eligible to receive salvage nivo (3mg/kg) /ipi (1 mg/kg) q3 wk x 4 doses followed by q4 wk nivo maintenance for up to 48 wks (Part B). All pts were required to submit tissue from a metastatic lesion obtained within 12 months (mo) prior to study entry and prior to Part B. Pathology specimens will be analyzed by immunohistochemistry, quantitative immunofluorescence, WES and RNAseq with results linked to clinical outcome. Results: 123 pts with clear cell(cc) RCC were enrolled between 5/2017 and 12/2019 at 12 participating HCRN sites. Median age 65 (range 32-86 years); 72% male. IMDC favorable 30 (25%), intermediate 79 (65%) and poor risk 12 (10%). 22 (18%) had a component of sarcomatoid histology (SARC). 117 pts are currently evaluable for response. RECIST defined ORR was: 34 (29.3%)[CR 5 (4.3%), PR 29 (24.8%)], SD 47 (40.2%), PD 36 (30.7%). ORR by irRECIST was 35%. ORR by IMDC was: favorable 12/29 (41.4%), intermediate/poor 22/87 (25.3%) and for SARC 6/22 (27.3%). Median DOR is 13.8 (10.9, NA) mo. Median PFS is 7.4 (5.5, 10.9) mo. 110 pts remain alive. 60 pts (54 PD, 6 pSD) to date were potentially eligible for salvage nivo/ipi (Part B), but 28 did not enroll due to symptomatic PD (17), grade 3-4 toxicity on nivo (8), other (3). 27 of 32 Part B pts are currently evaluable for efficacy and 30 for toxicity. Best response to nivo/ipi was PR (11%), SD (30%), PD (59%). ORR by irRECIST was 19%. Grade 3-5 Treatment-related AEs (TrAE) were seen in 35/123 (28)% on nivo with 1 death due to respiratory failure. Grade 3-4 TrAE were seen in 10/30 (33%) on nivo/ipi with 0 deaths. Correlative studies are pending. Conclusions: Nivo monotherapy is active in treatment naïve ccRCC across all IMDC groups. Toxicity is consistent with prior nivo studies. Salvage treatment with nivo/ipi after nivo monotherapy was feasible in 53% of pts with PD/pSD, with 11% responding. Clinical trial information: NCT03117309 .
Efficiency: Minimizing dose escalation steps by calculating human dosing preclinically.
Authors: Steve Gyorffy, Al Blunt, Gerald L. Messerschmidt
Journal: Journal of Clinical Oncology (2020)

e15622 Background: Historically, oncology drug development can take years to accomplish the goal of bringing new agents to patients. Scientific knowledge is evolving rapidly, transforming our understanding of the diseases at a rapid pace. This necessitates expedited drug development and approval to allow benefit for cancer patients. First-in-human administration to accelerated approval worthy data can efficiently occur in approximately two years, often in small very specific populations (individualized [precision medicine] therapy). The pre-clinical time period solidifies basic knowledge of mechanism of action, dosing, schedule, safety and efficacy both in vitroand in vivo, but adds to the development timeline of these products. Determining the correct dose has been identified by us and others as a critical issue that often leads to prolonged Phase 1 dose escalation in very expensive human testing environments.To optimize development timelines, we have targeted identification of dose (safe vs toxic and no benefit vs effective) as a critical area to define in these pre-clinical experiments. Methods: Tumor cell killing concentrations are essential to understanding the required lower limits and optimal amounts of drug available at the target cell (cancer or immune cell), with cognizant regard to toxicity in normal tissue, both a key focus of preclinical testing. Determining these concentrations in vivo are important data sources for this concept of “therapeutic index”. Defining the concentration for killing range and concentrations in total body water can then be used to calculate human starting dose that is within or near the beneficial anti-cancer concentration, but not at the predicted toxic concentration for normal human tissues. Results: By using a mathematical algorithm, we have developed a set of formula’s that can translate micro-molar or similar concentrations in vitro, and animal studies to human optimized dose escalation trials. This often involves predicting maximum tolerated dose (MTD) or optimal biologic dosing (OBD) for efficacy and safety rather than forcing the appearance of Dose Limiting Toxicities (DLT). Conclusions: This pre-clinical work has the potential to be able to decrease the in-human dose escalation time period and lead to more efficient development of novel therapeutics.
Safety/efficacy of a phase I/II study of SNS-301 added to pembrolizumab in patients with ASPH+ locally advanced unresectable or metastatic/recurrent squamous cell carcinoma of the head and neck (SCCHN).
Authors: William Smith, John Celebi, Robert Pierce, Alice Drumheller, Ildiko Csiki, Alain Patrick Algazi
Journal: Journal of Clinical Oncology (2020)

e18510 Background: SNS-301 is a first-in-class immune activating agent targeting human aspartyl (asparaginyl) β-hydroxylase (ASPH). ASPH is overexpressed in +20 tumor types. SNS-301 is an inactivated λ-bacteriophage, engineered to express a highly immunogenic fragment of ASPH fused to the phage gpD coat protein, previously shown to safely and effectively generate CD4, CD8 and B cell responses in a Phase I study (NCT04034225). Anti-PD-1 antibodies such as pembrolizumab and nivolumab can induce durable clinical responses in 13-16% SCCHN patients. While ASPH is frequently expressed in SCCHN, effective de novo responses to this tumor-specific antigen may be limited due to immune tolerance. Our hypothesis is that SNS-301 will break tolerance and trigger a significant anti-ASPH T-cell immune response, which in combination with anti-PD-1 blockade, will result in improved anti-tumor responses in this difficult-to-treat patient population. Methods: This is a Phase I/II study of SNS-301 delivered intradermally in combination with pembrolizumab. The population consists of 30 patients with ASPH+ locally advanced unresectable or metastatic/recurrent SCCHN who are actively receiving pembrolizumab or nivolumab for ≥12 weeks and have a best response of stable disease (SD) or first evidence of progressive disease (PD). A safety run-in will be performed for safety and any dose limiting toxicities (DLT) using a modified rolling six design prior to proceeding to full enrollment. Patients will provide a pre-SNS-301 tumor sample, an on-treatment tumor biopsy and an optional biopsy at PD to characterize the tumor microenvironment and correlate with clinical outcomes. SNS-301 in combination with pembrolizumab is given until confirmed PD or unacceptable toxicity. Study Objectives: Safety, tolerability and anti-tumor activity such as objective response rate, duration of response, progression-free and overall survival, immune responses, tumor/immune biomarkers and their associated treatment outcome. Results: Three patients have been enrolled. There have been no DLTs. Emerging safety data includes G1 adverse events with one G1 injection site pain. Patient status includes 1 PD and 2 patients with SD of at least six weeks duration. Immunological analyses will be presented. Conclusions: Early safety/efficacy warrant further evaluation of this combination therapy. Trial will be proceeding to full enrollment after the safety run-in is completed. Clinical trial information: NCT04034225.
平板运动试验诱发室上性心动过速一例
Authors: 彭旭东, 石亚君, 朱峰, 赵立朝, 卢喜烈
Journal: BMJ (2011)

患者男性,29岁,因阵发性心悸1年,间断胸闷、头晕20 d来院就诊.诉活动后心悸,休息10 min后可逐渐缓解,近20 d来无明显诱因出现胸闷、心前区不适伴头晕.既往无高血压、高脂血症、冠心病及糖尿病史。
Application of PD-1/PD-L1 immune checkpoint inhibitors treating lung cancer in Yerevan Armenia: Two-center experience.
Authors: Nune Karapetyan, Davit Zohrabyan, Jemma Arakelyan, Lilit Harutyunyan, Samvel Bardakhchyan, Armen Avagyan, Satenik Safaryan, Martin Harutyunyan, Liana Safaryan
Journal: Journal of Clinical Oncology (2020)

e15058 Background: Over the past few years PD-1/PD-L1 pathway blockade through immune checkpoint inhibitors appeared to be an effective treatment approach in advanced lung cancer. The current study aims to investigate the utilization of immunotherapy for lung cancer management purposes in Armenia. Methods: For this retrospective, hospital-based cohort study census sampling method was approached. Data was collected on all the patients who were diagnosed with stage III and IV lung cancer and passed treatment in the departments of Adult Solid Tumors in Hematology Center after prof. Yeolyan and Institute of Surgery after Mikaelyan from 01.05.2019 till 12.01.2020. The time period was selected based on the initiation of PD-L1 testing in Armenia. The prevalence of non-small cell (NSCLC) and small cell (SCLC) lung cancer was calculated. The patients’ PD-L1 testing performance, subsequent immunotherapy utilization, and developed adverse effects were evaluated. Results: According to the hospital-based data, during the mentioned time period 60 patients diagnosed with stage III and IV lung cancer received treatment in the two units. In the cohort, the patients’ median age was 65,5 years (range 46 – 88). The male-to-female ratio was 5.6. The prevalence of NSCLC and SCLC was 61.7% and 28.3% respectively. At the time of follow-up on 10.02.2020, 74.4% of NSCLC patients and 64.7% of SCLC patients were alive. Of the 43 NSCLC subjects, only 11 were checked for the PD-L1 status. Among them, 7 were determined to be PD-L1 positive and 5 of them received immunotherapy. For SCLC patients PD-L1 status wasn’t checked. Of 17 SCLC patients, only one has received immunotherapy. Overall only one case of immunotherapy related adverse effect was observed (severe rash and pruritus). At the time of follow-up, one of the six patients who underwent immunotherapy was dead. Conclusions: The presented data demonstrate a lack of PD-L1 test performance and underutilization of immunotherapy treatment. In the future, it is recommended to perform a nationwide study on the current topic to assess the immune checkpoint inhibitors impact on the survival rates of advanced lung cancer patients.
Distinct clinical and genetic characteristics of AFP-negative hepatocellular carcinoma patients infected by HBV or HCV.
Authors: Bixiang Zhang, Jingxian Duan, Yingmei Li, Zeyang Ding, Zhanguo Zhang, Shifu Chen
Journal: Journal of Clinical Oncology (2020)

e16620 Background: The serum level of alpha-fetoprotein (AFP) is a key biomarker in hepatocellular carcinoma (HCC) screening regardless of the high false-negative rates. Studies have characterized AFP negative HCC patients, however, the differences between HBV and HCV infected AFP negative HCC patients have not been discussed. Methods: The clinical profiles and whole-exome sequencing data of 243 patients were downloaded from the TCGA database. Patients were divided into 4 groups based on their virus infection status and serum AFP measurements as indicated in the table. The mutation profiles and clinical features of the patients were analyzed. Results: In the HBV infected groups, the AFP+ patients carried significantly larger tumors (n = 17, 85.88±11.87 mm) compared to the AFP- patients (n = 13, 49.08±8.933 mm, p = 0.026). The HBV+ AFP+ group exhibited the prevalence of vascular invasion (VI, 76%, 13/17) while less than half of the patients in the HBV+ AFP- group developed VI (46%, 6/13). The WES results identified shared mutations in more than 10% of patients in each group. It appeared that 126 shared mutations were restricted to the HBV+ AFP+ group, they are involved in the regulation of ion transmembrane transport (p &lt; 0.001) and interaction between L1 and Ankyrins (p &lt; 0.0001). Only 51 shared mutations were exclusive to the HBV+ AFP- group, they majorly affect developmental growth (p &lt; 0.001) and skeletal system development (p &lt; 0.01). In contrast, the tumor sizes of HCV+ AFP+ and HCV+ AFP- patients are similar (55.18±7.781 vs 48.19±5.564, p = 0.47), while the VI rate is higher in the HCV+ AFP- group (63%, 17/29, Table). In total, 11 shared mutations were restricted to the HCV+ AFP+ group, several of the genes were involved in the generation of precursor metabolites and energy (p &lt; 0.01) and activation of immune response (p &lt; 0.01). 27 shared mutations were exclusive to the HCV+ AFP- group, the enrichment analysis showed that they are related to the regulation of synapse organization (p &lt; 0.0001) and the regulation of chromosome organization (p &lt; 0.01). Conclusions: HBV and HCV infection were associated with distinct clinical features among the AFP positive and AFP negative patients. The differences were underpinned by the mutations exclusive to each group, and they were involved in distinct molecular and cellular functions. [Table: see text]
Implementation of a triage system in the <i>Alerta Rosa</i> breast cancer navigation program.
Authors: Cynthia Villarreal-Garza, Jaime Tamez-Salazar, Teresa Mireles-Aguilar, Cynthia De la Garza-Ramos, Marisol García-García, Ana Sofia Ferrigno, Alejandra Platas
Journal: Journal of Clinical Oncology (2020)

e19064 Background: Alerta Rosa is a navigation program in Nuevo Leon, Mexico that aims to reduce delays in breast cancer (BC) diagnosis and treatment initiation irrespective of healthcare coverage. Via a call center, a navigator registers each patient’s initial concern and schedules a medical evaluation. This study aimed to assess the implementation of a triage system to guide appointment prioritization for undiagnosed BC patients with abnormal breast findings or imaging studies. Methods: Women that contacted Alerta Rosa were stratified according to their clinical characteristics into three priority groups. Asymptomatic women seeking check-up information were classified as low-priority (“Green”), those with nonspecific symptoms (e.g. mastalgia) or indeterminate image studies (BIRADS 0) as intermediate-priority (“Yellow”), and patients with suspicious symptoms (i.e. palpable mass, nipple retraction or bloody discharge), abnormal image studies (BIRADS 3-5) or an established BC diagnosis as high-priority (“Red”) for an appointment. The triage system’s ability to detect undiagnosed BC was evaluated against the number of patients per category in whom BC was later confirmed. Differences in time from initial contact to first medical evaluation were explored with an independent t-test. Results: From December 2017 to 2019, 561 women with a median age of 44 years (range: 8-89) contacted Alerta Rosa. 369 (66%) reported breast symptoms, 92 (16%) sought check-up information, 68 (12%) had an indeterminate/abnormal image study and 32 (6%) had received a BC diagnosis and wanted a second opinion. Accordingly, 16% of patients were classified as “Green”, 25% “Yellow” and 59% “Red”. The median time from stratification to medical evaluation was 4 days for the “Red” group and 7 days for those in other categories ( p= 0.003). A total of 558 appointments were scheduled, of which 441 (79%) were attended. Excluding those who had received a prior BC diagnosis, 20/299 patients from the “Red” group had BC confirmed (6.7%) compared to 1/138 patient from the “Yellow” (0.7%) and none from the “Green” categories. Therefore, the “Red” category achieved a sensitivity of 95.2% (CI95%: 76.2-99.9%) and specificity of 53.8% (CI95%: 49.3-58.3%) for BC. Conclusions: The triage system adequately identified women with different probabilities of having BC. Thus, the implementation of a stratification system could help identify high risk patients in limited-resource settings where screening programs are ineffective and efforts to prioritize access to medical attention is crucial to achieve early-stage diagnoses.
Clinical analysis of 49 cases with Pseudo-Meigs′ Syndrome: a report of two cases and a review of literatures over the last decade
Authors: Wei Bian, Min Wei, Ling Xu
Journal: BMJ (2015)

Retrospective analyses were conducted for the clinical data of two cases with pseudo-Meigs′ syndrome at our hospital. Both had respiratory symptoms, such as cough and dyspnea. Radiological examinations revealed ascites, pleural effusion and pelvic mass. The definite pathological diagnosis was pelvic malignant tumor. After surgical tumor removal, ascites and pleural effusion disappeared without recurrence. Along with reviewed cases from PubMed in the last decade, a total of 49 cases had pseudo-Meigs′ syndrome. The age range was 11-73 years. Their clinical manifestations include dyspnea (78%), abdominal distension (69%), cough (14%), abdominal pain (12%), fatigue (10%), weight loss (6%) chest pain (4%), fever (4%), abdominal mass (4%), and oliguria (2%). CA125 was commonly elevated. The primary tumors in pelvic cavity accounted for 78%. And ovarian metastasis from colon cancer was one of the most common in metastatic tumors.


Key words: 
Pseudo-Meigs′ syndrome; Pleural effusion
Peripheral motor and sensory neuropathy in survivors of childhood central nervous system (CNS) tumors in the St. Jude Lifetime (SJLIFE) cohort.
Authors: Rozalyn L Rodwin, Lu Lu, Deo Kumar Srivastava, Tara M. Brinkman, Kevin R. Krull, Gregory T. Armstrong, Raja B. Khan, Nicholas S. Phillips, Thomas E. Merchant, Amar J. Gajjar, Leslie L. Robison, Melissa M. Hudson, Nina S. Kadan-Lottick, Kirsten K. Ness
Journal: Journal of Clinical Oncology (2020)

10549 Background: Survivors of CNS tumors are at risk for peripheral motor and sensory neuropathy. Chemotherapy’s contribution to peripheral neuropathy has not been well studied in this population. We aimed to estimate the prevalence of peripheral neuropathy, and determine its association with tumor characteristics and treatment exposures. Methods: Within the SJLIFE cohort, survivors of CNS tumors (n = 363, median [range] age 24 [18-53] years, 43.3% female) ≥10 years from diagnosis and ≥ 18 years at evaluation completed in-person assessments for peripheral motor and sensory neuropathy (defined as abnormal motor or sensory subscales of the Modified Total Neuropathy Score). For comparison, matched community controls (n = 445, median [range] age 34 [18-70] years, 55.7% female) underwent the same assessment. Prevalence of ≥ grade 2 motor or sensory neuropathy was estimated by a modified Common Terminology Criteria for Adverse Events. Multivariable analyses adjusting for age, sex and race were used to identify associated disease and treatment characteristics. Results: Overall, 11.0% of survivors of CNS tumors versus 0.9% of controls had ≥grade 2 motor neuropathy (p &lt; 0.001), and 15.7% of survivors of CNS tumors versus 2.3% of controls had ≥grade 2 sensory neuropathy (p &lt; 0.001). Prevalence of motor and sensory neuropathy varied by diagnosis (Table). Vinca alkaloid exposure (OR 3.5, 95% CI 1.7-7.0) and infratentorial tumor location (OR 2.5, 95% CI 1.1-5.4, reference supratentorial location) were independent risk factors for sensory neuropathy. Infratentorial tumor location was also associated with an increased risk of motor neuropathy (OR 2.4, 95% CI 1.2-4.8). History of radiation and surgery were not significant independent risk factors for motor or sensory neuropathy. Conclusions: Prevalence of peripheral motor and sensory neuropathy was significantly higher in survivors of CNS tumors than in matched community controls. Survivors of CNS tumors would benefit from increased surveillance to identify and treat peripheral neuropathy, especially in those who received vinca alkaloids or had infratentorial tumors. [Table: see text]