tbuckley/cabot-search huggingface dataset:
CT-based radiomic classifier of primary renal tumors to distinguish between metastatic and non-metastatic disease.
Authors: Sam O Kleeman, Michael Grant, Kathrine Sofia Rallis, Anna Wozniak, Alfred So, Resha Tejpaul, Nicholas Heller, Christopher J. Weight, Katherine Ordidge, Axel Bex, Anju Sahdev, Thomas Powles
Journal: Journal of Clinical Oncology (2020)

5074 Background: Existing clinicopathological tools are unable to accurately identify renal cell carcinoma (RCC) patients who will develop metastases after surgery. As a result, it is unclear how long and how often to follow-up patients post-operatively. Tumor macropathology, as assayed by CT scanning, represents the sum product of tumor biology and microenvironment. We hypothesized that quantitative tumor features extracted from CT scans (termed radiomics) could discriminate between metastatic and non-metastatic RCCs. Methods: This retrospective study incorporated three cohorts of clear-cell RCC patients (n = 279, from TCGA, CPTAC and KiTS19 datasets) treated with nephrectomy. The study cohort was sub-divided into metastatic (n = 54, M1 at diagnosis or recurrence after surgery), high metastatic risk/HMR (n = 85, N1, T3-4, T2G3/4, T1G4) or low metastatic risk/LMR (n = 140, absence of these features) subsets. 3D primary tumor segmentation of arterial contrast CT scans was performed by trained investigators. Features were extracted using pyRadiomics 2.2.0 (n = 839) with gray value and voxel size normalization. For random forest (RF) model training, the cohort was randomly split into training (75%) and validation (25%) sets. Results: Multidimensional clustering of radiomic features by t-SNE analysis showed that metastatic and HMR tumors predominantly cluster together, while LMR tumors cluster separately. Consistent with this, there were no differentially regulated radiomic features (DR-features) between HMR and metastatic tumors. In contrast, we identified 26 DR-features (adjusted p-value &lt; 0.05) between presumed-metastatic (n = 139, HMR and metastatic tumors) and LMR tumors, which were then used as input to a RF binary classifier. In the training set, the trained classifier discriminated between presumed-metastatic and LMR tumors with bootstrapped AUC = 0.81. In the validation set, the classifier discriminated subsets with AUC = 0.80. Conclusions: High-risk and metastatic tumors have similar radiomic properties, suggesting common biology driving metastasis in RCC. We propose a novel radiomic classifier that accurately distinguishes between presumed-metastatic and low-risk tumors. Further work will assess whether this tool can identify patients with micrometastatic disease at diagnosis, who may benefit from adjuvant therapy or closer, long-term surveillance.
Final overall survival (OS) results from SOLO2/ENGOT-ov21: A phase III trial assessing maintenance olaparib in patients (pts) with platinum-sensitive, relapsed ovarian cancer and a BRCA mutation.
Authors: Andres Poveda, Anne Floquet, Jonathan A. Ledermann, Rebecca Asher, Richard T. Penson, Amit M. Oza, Jacob Korach, Tomasz Huzarski, Sandro Pignata, Michael Friedlander, Alessandra Baldoni, Tjoung-Won Park-Simon, Gabe S. Sonke, Alla Sergeevna Lisyanskaya, Jae-Hoon Kim, Elias Abdo Filho, Ignace Vergote, Phil Rowe, Eric Pujade-Lauraine
Journal: Journal of Clinical Oncology (2020)

6002 Background: SOLO2 (ENGOT ov-21; NCT01874353) showed that maintenance therapy with the PARP inhibitor olaparib in pts with platinum-sensitive relapsed ovarian cancer (PSROC) and a BRCA mutation (BRCAm) led to a statistically significant improvement in median progression-free survival (PFS) of 13.6 months vs placebo (hazard ratio [HR] 0.30). Time to second progression or death significantly improved (Pujade-Lauraine et al Lancet Oncol 2017) and a quality-adjusted PFS benefit was seen (Friedlander et al Lancet Oncol 2018) with maintenance olaparib vs placebo. We report the preplanned final OS analysis for SOLO2. Methods: Pts with PSROC and a BRCAm who had received ≥2 lines of treatment and were in response to their most recent platinum-based chemotherapy received maintenance olaparib (300 mg bid tablets) or placebo. Pts were stratified by response to previous chemotherapy (complete vs partial) and length of platinum-free interval (&gt;6–12 months vs &gt;12 months). OS was a secondary endpoint. The only preplanned OS sensitivity analysis was an OS analysis in the Myriad germline BRCAm subset (Myriad BRAC Analysis test). Results: At final data cut-off (Feb 3, 2020), median follow-up was 65 months in both treatment arms. A long-term treatment benefit was seen with olaparib vs placebo with an OS HR of 0.74 (95% confidence interval [CI] 0.54–1.00) in the full analysis set (FAS; unadjusted for crossover; 38.4% of placebo pts crossed over to a PARP inhibitor) (Table). At 5 years: by Kaplan-Meier estimates, 28.3% of pts in the olaparib arm vs 12.8% of pts in the placebo arm were alive and had still not received subsequent treatment; 42.1% of olaparib pts vs 33.2% of placebo pts were alive. The long-term tolerability profile of olaparib was generally consistent with that reported previously. Conclusions: In the final analysis of SOLO2, maintenance olaparib provided an unprecedented improvement of 12.9 months in median OS vs placebo. This is the first study with olaparib tablets, and the first since Study 19 (NCT00753545), to provide long-term follow-up and final OS data in pts with PSROC and a BRCAm. Clinical trial information: NCT01874353. [Table: see text]
带状疱疹三例误诊分析
Authors: 赵志芳, 李智
Journal: BMJ (2007)

带状疱诊与水痘的病因同为水痘-带状疱疹病毒,近年来,随着人们生活节奏的加快,其发病率有所升高,并且误诊率也很高.该病好发于春秋季节,我所仅2006年4月就曾接诊过3例误诊病例.现将资料总结如下。
A prospective pilot study of pharmacogenetic-based dosing of 5-fluouracil (5-FU) and irinotecan (IRI) in patients (pts) with gastrointestinal (GI) malignancies.
Authors: Jeffrey Chi, Nausheen Hakim, Hasan Rehman, Linda Moriarty, Antonia Maloney, Melissa H Smith, Jyothi Jose, Wasif M. Saif
Journal: Journal of Clinical Oncology (2020)

e16138 Background: 5-FU and IRI are core components of chemotherapies for GI malignancies. Previous studies have shown that mutations in DPYP and TYMS predispose the pts to 5-FU toxicities. Mutations in UGT1A1 predispose pts to increased IRI toxicities. Retrospective data suggest that these mutations may have implications in selecting dosage and/or schedule of 5-FU and IRI. We present here a prospective study of upfront pharmacogenetic testing with tailored dose of respective drugs in pts with these mutations. Methods: Pts with GI malignancies were tested for DPYD, TYMS and UGT1A1 mutations before initiating 5-FU and/or IRI. Mutation analyses were performed at Quest Diagnostics Nichols Institute. Pts were dosed at 50% if DPYD was abnormal and 25% dose reduction if indicated by TYMS or UGT1A1 * 28 (homozygous) abnormality. Adverse events (AEs) were graded according to CTCAE v.5.0. We compared AEs to our previously collected data in DPYD, TYMS deficient pts who underwent genetic testing due to toxicity to 5-FU. Results: Of 226 pts screened, 5 pts had DPYP mutations with genotypes (3: c.1905+1G/A; 1: c.2846A/T; 1: c.557A/G). TYMS mutations were identified in 24 pts. For 3'-UTR, distributions were: intermediate expression genotype 4: INS/DEL, low expression genotype 5: DEL/DEL. For 5'TSER, distributions were: low expression genotypes (6:2R/2R; 3:2R/3RC; 4: 3RC/3RC) and high expression genotypes (2: 2R/3RG, 2: 3RG/3RC, 1: 3RG/3RG). UGT1A1*28 mutation was identified in 53 pts – 19 homozygous and 34 heterozygous. No grade ≥3 neutropenia was observed with reduced dose of IRI in UGT1A 1 variant pts compared to 33% reported in pts not tested. For TYMS and DPYD variants, no grade ≥3 AEs were seen. Comparison of AEs in pts with post treatment genetic testing is listed in Table. Conclusions: Pharmacogenetic based dosing of 5-FU and IRI led to less frequent, less severe toxicities and no death related to AEs was observed in our pts. This can improve pts’ quality of life and lessen economic burden of managing severe AEs. Currently, there are no formal guidelines regarding testing for DPYD, TYMS and UGT1A1. Although non-randomized, this study advocates for systemic screening of pharmacogenetic testing in pts with GI malignancies. [Table: see text]
Associations of regular glucosamine use with all-cause and cause-specific mortality: causality assumptions need to be checked
Authors: Saeid Safiri, Mohammad Ali Mansournia
Journal: Annals of the Rheumatic Diseases (2020)

We read with great interest the manuscript published by Li and colleagues that was published in the Annals of the Rheumatic Diseases in 2020.1 They evaluated the associations of regular glucosamine use with all-cause and cause-specific mortality in a large prospective cohort. This study provides valuable and interesting results but some methodological concerns should be taken into account.

First, they presented the results in term of two models (model 1 and model 2), but it is not clear how the models were built. The rationale for the confounder selection …
以肺囊肿为表现的肺癌一例
Authors: 姜波, 李晓东, 于炳强, 姜军永, 张忠松
Journal: BMJ (2009)

患者男,70岁.咳嗽、胸痛月余入院.体温38.3℃,右肺下部呼吸音略低.血常规:白细胞17.9×109/L,分类中性粒细胞0.84,淋巴细胞0.08.肺部CT:右肺下叶类圆形低密度灶,约8.9 cm×6.7 cm,边缘光滑,CT值约16 Hu,中心密度不均匀,可见多发气体影.病灶穿刺抽出浑浊脓性液约100 ml,常规化验:脓性,淡红,浑浊,无凝块,李凡他试验(+).红细胞计数0.17×1012/L,白细胞4.17×109/L,分类中性粒细胞0.87,淋巴细胞0.11。
Correlation of substantia nigra hyperecho with essential tremor and Parkinson disease
Authors: Hongling Gao, Zheng Xue, Anyu Tao, Qingmei Yang, Zhijuan Mao
Journal: BMJ (2019)

Objective
To investigate the correlation of substantia nigra hyperecho with essential tremor (ET) and Parkinson disease (PD).


Methods
The clinical data of 158 patients with ET or PD who underwent transcranial ultrasonography in Tongji Hospital from March 2016 to March 2018 were retrospectively analyzed. There were 35 patients with ET (ET group), 113 patients with PD who had no previous history of ET (PD group), and 10 PD patients with previous history of ET (ET-PD group). And 58 healthy subjects served as controls (control group). The hyperechoic area of substantia nigra in different groups was compared.


Results
The hyperechoic areas of the substantia nigra were [0 (0, 0)]cm2 (control group), [0.27(0, 0.41)]cm2 (ET group), [0.33(0.21, 0.40)]cm2 (ET-PD group) and [0.35(0.29, 0.45)]cm2 (PD group); the differences between control group and ET group, between the ET group and PD group were statistically significant (Z=-5.24, P=0.01; Z=-3.09, P=0.02), and there were no significant difference between the ET group and ET-PD group, between ET-PD group and PD group (Z=-0.98, P=0.32; t=-0.98, P=0.33). The ratio of substantia nigra hyperechoic positive to negative in ET-PD group was 9.00 (9/1), while that in ET group was 0.94 (17/18) (OR=9.53, 95% CI: 1.09-83.43, χ2=3.91, P=0.04).


Conclusion
Substantia nigra hyperecho is an objective imaging indicator for patients with ET and PD, and has a certain differential value for their diagnosis.


Key words: 
Essential tremor; Parkinson disease; Substantia nigra; Ultrasonography, Doppler, transcranial
Analgesic efficacy of methylene blue with ropivacaine on anorectal disease postoperation
Authors: Yong-hui Su, Bing-zong Hou, Ju-yuan Bu, Xiao-ling Li
Journal: BMJ (2013)

Between January 2011 and December 2011, 86 patients undergoing operation for anorectal disease were randomized in a double-blind manner to receive a mixed injection of methylene blue, ropivacaine and sodium chloride (observation group, n=43) or traditional analgesic methods (control group, n=43). Patients in observation group had less visual analog scale (VAS) scores of pain at 6-48 h postoperation than control group (P 0.05). The total postoperative complications (8, 19%) and hospitalization duration [(5.3±2.2) days] in observation group were significantly less than those [15, 35% and (6.4±1.7) days] in control group (P<0.05). A mixed injection of methylene blue and ropivacaine intraoperatively can relieve the postoperative pain of patients with anorectal disease and reduce the incidence of postoperative complications and the duration of hospitalization.


Key words: 
Anus diseases; Methylene blue
Enrollment barriers of adolescents and young adults (AYA) on the non-chemotherapy arm of ARST1321.
Authors: Lisa M. Kopp, Damon R. Reed, Safia K. Ahmed, Wendy Allen-Rhoades, Viswatej Avutu, Yen-Lin Chen, Lara E. Davis, Bree Ruppert Eaton, Douglas S. Hawkins, Daniel J. Indelicato, Shreyaskumar Patel, R. Lor Randall, Denise K. Reinke, Richard F. Riedel, Thomas Scharschmidt, Katherine Anne Thornton, Dian Wang, Katherine A. Janeway, Aaron R. Weiss
Journal: Journal of Clinical Oncology (2020)

e19214 Background: ARST1321(PAZNTIS): A Phase II/III Randomized Trial of Preoperative Chemoradiation or Preoperative Radiation Plus or Minus Pazopanib (NCT02180867) was the first National Clinical Trials Network (NCTN) study co-developed by pediatric (COG) and adult (NRG Oncology) consortia anticipating enrollment of adolescent and young adult (AYA) cancer patients. ARST1321 had two treatment cohorts, enrolling patients ≥ 2 years of age to either chemotherapy (C) (chemoradiation ± pazopanib) or non-chemotherapy (NC) (radiation ± pazopanib) arms. It was anticipated adults would contribute the majority of enrollments on the NC arm based on prior enrollment patterns. While the C arm accrued as anticipated (with high enrollment of adults and children), the NC arm had low enrollment leading to premature closure. We report on AYA accrual (defined as 15-39 years) to the NC arm and a survey aiming to identify barriers to enrolling AYA patients onto ARST1321. Methods: Our survey was emailed to 161 adult, surgical, and radiation oncologists at large sarcoma centers. A link was sent to an online questionnaire via SurveyMonkey Inc. and responses were reviewed on their platform. Results: 33 patients enrolled on the ARST1321 NC arm, of which 24% were AYA. 25% of AYA enrollments were from non-COG adult cooperative groups. This trial arm was closed in October 2017 after 3.25 years of accrual below anticipated rates. The survey response rate was 31% with a 70% completion rate. Almost half of respondents were medical oncologists with most seeing 50-200 new sarcoma cases/year at an academic institution and 30% in a pediatric environment (divided equally between radiation and surgical oncologists). 70% of respondents have a joint collaboration with their pediatric oncology team with 23% having a joint clinic. 70% of respondents’ sites opened ARST1321 and anticipated 1-5 patients would be eligible for the NC cohort. However, 42% of respondents’ sites had zero patients enrolled on that arm. The most common reasons for not opening the study and/or not enrolling patients on the NC arm included: lack of interest, disagreement with the therapy, lack of a site investigator, premature study closure, patient/family decision, competing trials, insufficient reimbursement, and regulatory delays. Conclusions: Our survey highlights multiple barriers to enrollment of AYA onto cross-NCTN consortia clinical trials spanning the age spectrum. The information obtained will help inform investigators aiming to effectively design, enroll, and conduct similar trial efforts for AYA in the future.
Prognostic Value of Magnetic Resonance Phenotype in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Giovanni Donato Aquaro, Antonio De Luca, Chiara Cappelletto, Francesca Raimondi, Francesco Bianco, Nicoletta Botto, Pierluigi Lesizza, Crysanthos Grigoratos, Monia Minati, Matteo Dell’Omodarme, Alessandro Pingitore, Davide Stolfo, Matteo Dal Ferro, Marco Merlo, Gianluca Di Bella, Gianfranco Sinagra
Journal: Journal of the American College of Cardiology (2020)
A new desensitization protocol, overcoming hypersensitivity reactions to chemotherapy.
Authors: Andrei Dan Havasi, Calin Ioan Cainap, Ioan-Cătălin Vlad, Patriciu Achimaş-Cadariu, Daniel Genel Sur, Andra Meşter (Piciu), Ana Teodora Heputiu-Pater, Ovidiu Bochis, Ovidiu Balacescu, Ovidiu Crisan, Ovidiu Coza, Loredana Balacescu, Claudia Cristina Burz, Simona Sorana Cainap
Journal: Journal of Clinical Oncology (2020)

e15523 Background: Despite the progress for cancer treatment, some drugs remain a cornerstone for an optimal approach. Hypersensitivity reactions to chemotherapy may render these essential chemotherapeutic agents useless and for some types of cancer continuing the therapeutic scheme could be crucial. Various regimens for desensitization to allow chemotherapy administration through the time were conceived, with different dilutions, time and settings of administration. Methods: A prospective study of patients with systemic treatment for histopathologically confirmed cancer in our Oncological Institute „Prof. Ion Chiricuta” Cluj-Napoca, with an allergic reaction during treatment being the keys inclusion criteria in the analysis. Patients were administered a three days desensitization regimen from the following cycle of treatment with blood samples that were taken to observe the predictive value of biological markers. Results: Eighty-two patients were the initial pool, with a median age of 56 years. Platin derivates containing regiments were responsible for an allergic reaction for 75 out of 82 patients. Four of them were known with a previous allergic reaction for chemotherapy in their personal medical history, and 56 of them had more than one chemotherapy line in their treatment. More than 688 desensitization cycles were administrated during our study with a rate of failure of 1.3 %. The main reason for discontinuation was disease progression or adjuvant character (limited duration) of the chemotherapy administration. Conclusions: Allergic reaction does not impede the administration of the responsible drug. A 3-day inpatient regimen could be a valuable option with a successful rate of administration without the need for ICU monitoring.
从发展的角度看急诊室的布局与功能
Authors: 杨诚
Journal: BMJ (2005)

我于2003年8月至9月赴澳学习期间,特别观察了几家医院在急诊方面的工作情况,感触颇深,尤其是在布局功能及人文关怀方面值得借鉴.以墨尔本地区最大的州属公立医院圣文森医院为例,该院位于市中心,共计500张床位,以擅长普外科著名,相当于北京一所普通的三级甲等医院,但澳州人口稀少,该院规模为当地最大医院.其急诊工作系统堪称一流,简要介绍如下。
Diabetes mellitus in childhood and young adult cancer survivors: A meta-analysis.
Authors: Igal Kushnir, Dominika Bhatia, Amirrtha Srikanthan, Iliana Lega
Journal: Journal of Clinical Oncology (2020)

e24101 Background: Diabetes mellitus (DM) has emerged as a possible late sequela after successfully treating pediatric and young adult (YA) malignancies. We conducted a systematic review and meta-analysis in order to quantify this risk and assess possible risk factors. Methods: We searched MEDLINE and EMBASE databases from inception to April 2019. We included cohort or case-control studies that reported the risk of DM (hazard ratio [HR], relative risk, or odds ratio, and 95% confidence interval [CI]) among childhood and YA cancer survivors ( &lt; age 21 years) compared to those without a history of childhood or YA cancer. We used the Newcastle-Ottawa Score (NOS) to assess risk of bias and study quality. Study effect estimates were pooled using random-effects meta-analyses. Heterogeneity was assessed using the I 2 statistic. Results: After applying our exclusion/inclusion criteria, we included 6 articles in our meta-analysis, with a median follow-up time of 11 (range 10-23) years. The median NOS score was 8 (range 7 – 8), indicating high study quality. The risk of DM was significantly higher in childhood and YA cancer survivors relative to controls (HR 1.66, 95% CI 1.54 to 1.79, I 2 = 1%). Among cancer types, the highest risk for DM was reported after treatment for leukemia (HR 2.91, 95% CI 2.01 to 4.22 I 2 = 75%), lymphoma (HR 1.63, 95% CI 1.37 to 1.94, I 2 = 0%) and central nervous system malignancies (HR 1.77, 95% CI 1.30 to 2.39, I 2 = 49%), relative to controls. Receiving total body irradiation or abdominal radiation was associated with a DM risk of 4.52 (95% CI 2.29 to 8.93, I 2 = 87%), relative to controls. Conclusions: Our meta-analysis demonstrated an increased risk of developing DM among childhood and YA cancer survivors. More emphasis on screening for DM and prevention among this population should be offered.
Pyrotinib combined with capecitabine as first-line therapy for HER2-positive metastatic breast cancer: A pooled analysis of three randomized controlled trials.
Authors: Zefei Jiang, Binghe Xu, Min Yan, Quchang Ouyang, Xi-Chun Hu, Wei Li, Ji Feng Feng, Qingyuan Zhang, Zhongsheng Tong, Ping Yan, Xiaoyu Zhu, Shangyi Rong, Jianjun Zou
Journal: Journal of Clinical Oncology (2020)

e13022 Background: Anti-HER2 agents combined with chemotherapy is the treatment strategy for treatment-naive HER2-positive relapsed or metastatic breast cancer. This pooled study was conducted to investigate the efficacy of pyrotinib plus capecitabine as first-line treatment in patients with HER2-positive relapsed or metastatic breast cancer. Methods: Data were derived from three randomized controlled trials. In the phase 2 (NCT02422199) and the PHOEBE phase 3 (NCT03080805) studies, patients were randomized to receive pyrotinib plus capecitabine or lapatinib plus capecitabine. In the PHENIX phase 3 (NCT02973737) study, patients were randomly assigned and given pyrotinib plus capecitabine or placebo plus capecitabine. Patients who had received neither anti-HER2 agents nor chemotherapy for the relapsed or metastatic disease were included in the analyses, and the pooled tumor response data (per blinded independent central review) were reported herein. Results: In the pooled analysis of all three studies, 145 patients received pyrotinib plus capecitabine. The median progression free survival (PFS) was 12.4 months (95% CI, 11.1 months to not reached). The objective response rate (ORR) reached 72.4% (95% CI, 64.4% to 79.5%). In the pooled analysis involving the phase 2 and PHOEBE phase 3, 84 patients were treated with pyrotinib plus capecitabine and 62 patients with lapatinib plus capecitabine. The PFS was significantly prolonged with pyrotinib plus capecitabine vs lapatinib plus capecitabine (median, 12.4 months [95% CI, 11.1 months to not reached] vs 8.2 months [95% CI, 5.5 to 9.7 months]; hazard ratio, 0.40 [95% CI, 0.25 to 0.66]; p = 0.0001). The ORR was 71.4% (95% CI, 60.5% to 80.8%) with pyrotinib plus capecitabine compared with 58.1% (95% CI, 44.8% to 70.5%) with lapatinib plus capecitabine. Conclusions: The pooled analysis demonstrated pyrotinib plus capecitabine was efficacious as first-line therapy in patients with HER2-positive relapsed or metastatic breast cancer, offering a potent treatment option for these patients.