tbuckley/cabot-search huggingface dataset:
ALTERNATE: Neoadjuvant endocrine treatment (NET) approaches for clinical stage II or III estrogen receptor-positive HER2-negative breast cancer (ER+ HER2- BC) in postmenopausal (PM) women: Alliance A011106.
Authors: Cynthia X. Ma, Vera J. Suman, A. Marilyn Leitch, Souzan Sanati, Kiran R. Vij, Gary Walter Unzeitig, Jeremy Hoog, Mark Watson, Olwen Mary Hahn, J. Michael Guenther, Abigail Suzanne Caudle, Travis Dockter, Larissa A. Korde, Anna Weiss, Kelly Hunt, Clifford A. Hudis, Eric P. Winer, Ann H. Partridge, Lisa A. Carey, Matthew James Ellis
Journal: Journal of Clinical Oncology (2020)

504 Background: For PM patients (pts) with locally advanced ER+ HER2- BC, NET improves breast conservation surgery (BCS) rates, and modified preoperative endocrine prognostic index (mPEPI) 0, defined as pT1-2 pN0 Ki67&lt; 2.7%, or pathologic complete response (pCR: no invasive disease in breast or lymph node) is associated with low risk of recurrence without adjuvant chemotherapy (CT). The ALTERNATE trial was initiated to assess if the endocrine-sensitive disease rate (ESDR: number of mPEPI 0 pts/number of eligible pts initiating NET) with fulvestrant (F) or F+anastrozole (A) is improved relative to A alone (reported here) and if the 5-year (yr) recurrence-free survival (RFS) rate for pts with mPEPI 0 on A alone without CT is ≥ 95% (awaits further follow-up). Methods: PM pts with clinical stage II/III ER+ HER2- BC were randomized 1:1:1 to 1 mg A po daily, 500 mg F IM every 4 week (wk)s after loading dose, or A+F for 6 months. Ki67 was tested centrally on biopsies acquired prior to NET, wk 4, wk 12 and at surgery. Pts with Ki67 &gt;10% at wk 4 or 12 were recommended to go off protocol-directed ET and switch to CT. Pts with mPEPI 0 at surgery were recommended to continue assigned ET for 1.5 yrs followed by A for a total of 5 yrs ET (and not to receive CT). The primary endpoint of the neoadjuvant phase was ESDR. ESDR of each F arm was compared to that of the A alone arm. With 425 pts per arm, a one-tailed alpha = 0.025 chi-square test of two independent proportions has 84% power to detect an increase of ≥10% in ESDR for F or F+A compared to the A arm, assuming ESDR ≤30% in A. Results: 1362 pts (A 452; F 454; A+F 456) were enrolled Feb 2014 to Nov 2018. 63 pts were excluded (did not start NET). Of the remaining 1299 pts (A 434; F 431, A+F 434), 42% were cN1-3 and 73% were considered candidates for BCS. ESDR was 18.6% (95%CI: 15.1-22.7%) with A, 22.7% (95%CI: 18.9-27.0%) with F, and 20.5% (95%CI: 16.8-24.6%) with A+F. No significant difference in ESDR was found between A and F (p=0.15) or A and A+F (p=0.55). Among the 825 pts with wk 4 Ki67 &lt; 10% who completed NET and surgery, ESDR and the BCS rate were 27.7% and 70.3% with A; 29.6% and 68.1% with F, and 26.8% and 69.9% with A+F, respectively. Conclusion: Neither F nor F+A significantly improved ESDR compared to A alone in PM pts with locally advanced ER+ HER2- BC. RFS data are awaited. Support: U10CA180821, U10CA180882, U24CA196171, https://acknowledgments.alliancefound.org ; NCI BIQSFP, BCRF, Genentech, AstraZeneca. Clinical trial information: NCT01953588 .
Evaluation of an AI system for breast cancer screening in mammograms of young women.
Authors: Daniel Gustavo Pellacani Petrini, Gabriel Vansuita Valente, Carlos Shimizu, Rosimeire Aparecida Roela, Gabriel Miranda de Araújo, Tatiana Cardoso de Mello Tucunduva, Maria A. A. Koike Folgueira, Hae Yong Kim
Journal: Journal of Clinical Oncology (2020)

e14068 Background: The interpretation of the mammography is challenging, especially in young women, who have dense breasts. Artificial intelligence (AI) promises to improve breast cancer detection; however these systems should be tested on different datasets. Our aim is to evaluate the performance of a publicly available deep convolutional neural network, developed by Wu et al. (IEEE Trans. Med. Imaging, 2019), applied to mammograms of young women. Methods: The test dataset consisted of mammograms obtained on a single occasion from 135 young women (up to 40 years old) on a Siemens mammography system. Each exam consisted of 4 full-field digital mammography images and had two labels (left malignant and right malignant). Mammograms were analyzed by a single mammography trained radiologist, using BI-RADS reporting tool. Among 270 labels, 170 were malignant and 100 were non-malignant. We used the program developed by Wu et al. that, according to the authors, presents AUC of 0.895 for the general population. As a preliminary test, we ran this program in a publicly available dataset named INbreast and obtained AUC of 0.8708, very close to the result reported by the authors. Results: We applied the program to our dataset of young women and obtained AUC of 0.876. We computed its standard error, obtaining 0.0290. At equal error rate point of the ROC curve, specificity and sensitivity are both 0.774. With this result we conclude that, at least for our dataset, cancer detection in young women is not substantially more difficult than in general population for an AI system. We fine-tuned the weights of the original network to the population of young women using transfer learning and obtained a slight improvement in AUC: 0.9018±0.0528, where the mean and the standard error were obtained using 5-fold cross validation. As the improvement was small and the standard errors are large, we would have to test on a larger test set to ensure that the observed improvement is real. Conclusions: We conclude, based on the experimental data, that there is no substantial degradation in accuracy when a mammogram screening program for general population is used for young women. We also conclude that it seems to be possible to obtain a slight improvement in accuracy by fine-tuning the network for the population of young women.
The Integration of PD1 blockade with epigenetic therapy is highly active and safe in heavily treated patients with T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL).
Authors: Enrica Marchi, Helen Ma, Francesca Montanari, Ahmed Sawas, Jennifer K Lue, Changchun Deng, Kareema T Whitfield, Sandra Klein, Luigi Scotto, Salvia Sanjay Jain, John Lister, Nora N Benanni, Mark A Francescone, Wonseog S Kim, Pier Luigi Zinzani, Owen A. O'Connor
Journal: Journal of Clinical Oncology (2020)

8049 Background: Our group has demonstrated that combinations of epigenetic modifiers produce potent synergy in pre-clinical models of PTCL and induce the expression of cancer testis antigen, suggesting a role in the addition of the immune-checkpoint inhibitor, pembrolizumab. Methods: This is a phase 1b study of pembrolizumab combined with pralatrexate alone (Arm A), with pralatrexate + decitabine (Arm B), or decitabine alone (Arm C) in patients with relapsed and refractory PTCL and CTCL. A standard 3+3 dose-escalation is applied in the triplet Arm (Arm B) while in the doublet Arms (A and C) de-escalation is applied in case of toxicity. Pharmacokinetic and pharmacodynamic studies are ongoing. Results: We treated a total of 12 patients with 4 patients in each Arm. All patients that received at least one dose of drug were evaluable for toxicity. There was a dose limiting toxicity (DLT) in each arm including prolonged grade 3 thrombocytopenia (Arm A), febrile neutropenia (Arm B), grade 3 hyponatremia, and rash (Arm C). There were no treatment-related deaths. Six patients out of 12 were evaluable for response at the time of this analysis. One patient achieved a complete remission, 2 had partial remission, 1 had stable disease, and 2 experienced progression of disease. Interestingly, all of the responses were seen in the triple combination of pralatrexate, decitabine, and pembrolizumab. Table summarizes the patient characteristics, toxicities, and response rates. Conclusions: These preliminary clinical data suggest that the integration of pembrolizumab on an epigenetic backbone is safe and demonstrates encouraging responses in patient with PTCL and CTCL. Clinical trial information: 03240211 . [Table: see text]
Effect of operation time on efficacy for patients with hypertensive basal ganglia hemorrhage
Authors: Xinghua Wang, Chuanlin Ji
Journal: BMJ (2016)

Two hundred and twenty patients with hypertensive basal ganglia hemorrhage(HBGH)undergoing cranial drilling operation and placement of soft catheter for drainage were enrolled. Among all patiems, the operation was performed at ≤6 h of disease onset in 92 cases (ultra-early group) , 6-24 h in 74 cases (early group) and >24 h in 54 cases (selective group). The surgery-related complications, near-term outcome and long-term outcome were compared among three groups. In ultra-early group, recurrent hemorrhage was observed in 26 cases (28%), which was higher than that in other two groups. In selective group, there were 11 cases (20 %) of well recovered, 19 cases (35%) of moderate deformity, 16 cases (30%) of severe deformity, 5 cases(9%)of vegetative state and 3 fatal cases(6%)indicating that the near-term outcome was worse than those other two groups . However there was no significant difference in long-term outcome among three groups. The rapid minimal invasive cranial drilling and soft catheter drainage is a safe and effective operation for HBGH patients and the optimal time for operation is 6-24 hours.


Key words: 
Cerebral hemorrhage, basal ganglia; Rapid pore cranial drilling; Operation time
Mutational profiles of lung adenocarcinoma subtypes.
Authors: Shuai Chang, Yan Wang, Yi Wang, Kun Zhou, Guowei Che
Journal: Journal of Clinical Oncology (2020)

e21517 Background: Genomic profiling of lung adenocarcinoma has been studied, however, different histological subtypes were not carefully distinguished, especially in patients with mixed subtypes. Methods: Fifty-three invasive adenocarcinoma (IA) FFPE samples from lung cancer patients with detailed histological classifications were panel sequenced and analyzed. Results: Among the 53 IAs, acinar (n = 42), lepidic (n = 34) and papillary (n = 25) were most dominant subtypes and were frequently mixed with other types. Zero to 14 mutations were identified in each sample (median = 4). Thirteen of the 42 (31%) tumors containing acinar subtype harbored TP53 mutations, while none of the 11 (0%) acinar negative tumors harbor TP53 mutation; six of the 42 (14.3%) acinar positive had RBM10 mutations, while 5 of the 11 (45.4%) acinar negative had RBM10 mutations. Three of the 34 (8.8%) tumors with lepidic subtypes harbored TP53 mutations, while 10 of the 19 (52.6%) lepidic negative tumors harbored TP53 mutations; Ten of 34 (29.4%) lepidic positive tumors harbored RBM10 mutations, while 1 of the 19 (5.3%) lepidic negative tumors harbored RBM10 mutations. All papillary tumors were mixed with other subtypes. Conclusions: Different histological subtypes have different mutational features. Acinar subtypes harbor more TP53 and less RBM10 mutations than acinar negative tumors; lepidic subtypes harbor less TP53 and more RBM10 mutations than lepidic negative tumors. Lack of mucinous, micropapillary and solid subtypes requires further study to analyze their mutational signatures.
Abstract 14532: microRNA-126 is a Regulator of Platelet-Mediated Thrombin Generation
Authors: Veronika Zapilko, Richard Fish, Alix Garcia, Jean-Luc Reny, Sylvie Geindre, Marguerite Neerman-Arbez, Pierre Fontana
Journal: Circulation (2018)

Introduction: Platelets are an important source of microRNAs (miRNAs). Platelet miRNA expression profiles correlate with platelet reactivity, which raises the possibility of finding novel miRNA-bas...
Influence of chronic neuropathic pain on VEGFA in tumors of mice with genetically determined inhibition of tumor growth.
Authors: Elena M. Frantsiyants, Irina V. Kaplieva, Ekaterina I. Surikova, Irina V. Neskubina, Valeria A. Bandovkina, Lidia K. Trepitaki, Natalia D. Cheryarina, Ludmila A. Nemashkalova, Natalia S. Lesovaya, Viktoria V. Pozdnyakova, Yuriy V. Przhedetskiy, Olga V. Khokhlova, Viktoria Yu. Przhedetskaya, Natalia A. Zakharova, Oleg I. Kit, Natalya D. Ushakova
Journal: Journal of Clinical Oncology (2020)

e22103 Background: Chronic neuropathic pain (CNP) demonstrates the ability to stimulate tumor growth and neoangiogenesis. Our purpose was to study VEGFA levels in the growth of B16/F10 melanoma with CNP in mice with genetically determined inhibition of tumor growth. Methods: Females of С57ВL/6 mice (normal genome (uPA+), n = 26) and C57BL/6-Plautm1.1BugThisPlauGFDhu/GFDhu mice (urokinase gene knockout (uPA–), n = 16) received subcutaneous transplantation of B16/F10 melanoma 2 weeks after bilateral sciatic nerve ligation (CNP model). After 3 weeks of carcinogenesis in CNP, tumor volumes were measured and levels of VEGFA were studied in tumors by ELISA. Results: Tumor volumes in (uPA+) females with CNP in week 3 of carcinogenesis were similar to that in (uPA+) females without CNP and were on average 2.6 cm 3 (2.5 and 2.8 cm 3 respectively). Tumor volumes in (uPA–) females were 0.04 cm 3 , i.e. 70 times lower (p &lt; 0.001) than in (uPA+) females without CNP. Tumor volumes in (uPA–) females with CNP were 144 times higher (p &lt; 0.001) than in (uPA–) females without CNP and were 5.76 cm 3 . VEGFA levels in tumors of (uPA+) females with CNP were 11.1 times higher (p &lt; 0.001) than in (uPA+) females without CNP. VEGFA in tumors of (uPA–) females with CNP was 5.2 times higher (p &lt; 0.001) than in (uPA–) females without CNP. Conclusions: The CNP state showed higher VEGFA concentrations in tumor tissues of female mice with normal genome and uPA-deficient females (with genetically determined inhibition of tumor growth) which may cause a larger tumor volume in (uPA–) female mice.
复杂疑难病的突破口:病史
Authors: 金世红, 周仲华
Journal: BMJ (2012)

全科医生在医疗工作中的第一线需要经常面对一些未分化出疾病方向的症状,会遇到各种各样的患者,患者有时会表现出让人觉得不可思议的复杂症状,但是临床经验以及科学研究都告诉我们:诊断复杂疑难病的最终的突破口往往是在最基本的病史上。
Patterns of inpatient palliative care consultation for patients with brain and spine metastases.
Authors: Elizabeth Howell, Meghan Price, Tara Dalton, Theresa Williamson, Arif Kamal, Rory Goodwin
Journal: Journal of Clinical Oncology (2020)

e24117 Background: Patients diagnosed with brain and/or spine metastases (BSM) face high symptom burden and complex clinical decision-making. Through expertise in pain and symptom management, facilitation of end-of-life planning, and caregiver support, specialty Palliative Care (PC) can provide a crucial component of the care for these patients. No prior study has formally evaluated the rates of inpatient PC referral in BSM patients, nor the patient-specific factors that may affect consultation rates within this context. Methods: Analysis was performed of the rates of PC consults in a cohort of BSM inpatients admitted to three tertiary medical centers: one major academic center and two smaller affiliate centers. Patients were identified using a combination of ICD-9 and -10 codes and surgical provider lists to aggregate brain and spine metastases patient cohorts at each institution. Patient demographics, surgical status, and readmission data were collected. PC utilization was assessed by flagging encounters within which an inpatient consult to PC was placed. Results: 2608 total discharges were analyzed, with 2397 brain metastasis and 301 spine metastasis discharges. Average rate of inpatient PC consultation over the 3.5 year study period was 13.6% for brain metastasis patients and 11.0% for spine metastases patients. Rates of PC utilization differed significantly by patient race (11.6% in white vs. 17.0% in non-white patients, p = 0.02). Patients who received surgery had significantly lower rates of PC consultation in both brain (3.5% vs 15.6%, p &lt; 0.001) and spine (5.5% vs 14.1% p &lt; 0.001) cohorts. The large academic center had the lowest utilization as compared to two smaller affiliate centers, with 6.4% of brain and 7.6% of spine metastasis patients receiving PC consults. For both cohorts, Neurology was the discharging service with the highest rates of PC utilization, consulting PC for 37.7% of brain and 42.9% of spine metastasis patients respectively. Over time, PC utilization increased for brain, but not spine, metastasis patients. Conclusions: Despite their high symptom burden and low overall survival, BSM patients have low rates of inpatient PC consultation. Utilization appears to vary by patient demographics and surgical status, as well as discharging service and practice setting. These single-institution patterns may ultimately provide a microcosm for national patterns and trends at similar institutions, and further work is needed to identify the specific barriers to optimally utilizing specialty PC in this population.
A comparison of different protocols in treatment of infant asthma at severe attack
Authors: Zheng-hai Qu, Shuang Hong, Li Zhou, Shu-yu Che, Xiu-mei Liu
Journal: BMJ (2010)

Eighty one infants with severe asthma attacks were randomly divided into three groups:budesonide group (budesonide suspension + ventolin inhalation),methylprednisolone group (Ventolin inhalation + intravenous methylprednisoloue) and ventolin group (ventolin inhalation alone).Compared with the pre-treatment,the respiratory rate,heart rate,wheeze score,self-feeling score of three groups were gradually reduced (q=2.96-163.37,P＜0.05 or 0.01).The respiratory rate,heart rate of ventolin group was significantly higher than those of budesonide group (q=3.08,4.10,P＜0.05) and methylprednisolone group (q=3.24,3.34,P＜0.05) 4 h after treatment,wheeze score,self-feeling score of ventolin group was significantly higher than budesonide group (q=5.63-23.63,P＜0.01) and methylprednisolone group (q=6.76-23.72,P＜0.01) 4 and 12 h after treatment.Results indicate that budesonide suspension can achieve the same effect as intravenous methylprednisolone and bronchodilators alone may not effectively control the severe asthma attack in infants.

Key words: 
Asthma; Treatment outcome
Development and Validation of a Tool to Assess the Quality of Clinical Practice Guideline Recommendations
Authors: Melissa C. Brouwers, Karen Spithoff, Kate Kerkvliet, Pablo Alonso-Coello, Jako Burgers, Francoise Cluzeau, Beatrice Férvers, Ian Graham, Jeremy Grimshaw, Steven Hanna, Monika Kastner, Michelle Kho, Amir Qaseem, Sharon Straus, Ivan D. Florez
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Clinical practice guidelines (CPGs) may lack rigor and suitability to the setting in which they are to be applied. Methods to yield clinical practice guideline recommendations that are credible and implementable remain to be determined. <h3>Objective</h3> To describe the development of AGREE-REX (Appraisal of Guidelines Research and Evaluation–Recommendations Excellence), a tool designed to evaluate the quality of clinical practice guideline recommendations. <h3>Design, Setting, and Participants</h3> A cross-sectional study of 322 international stakeholders representing CPG developers, users, and researchers was conducted between December 2015 and March 2019. Advertisements to participate were distributed through professional organizations as well as through the AGREE Enterprise social media accounts and their registered users. <h3>Exposures</h3> Between 2015 and 2017, participants appraised 1 of 161 CPGs using the Draft AGREE-REX tool and completed the AGREE-REX Usability Survey. <h3>Main Outcomes and Measures</h3> Usability and measurement properties of the tool were assessed with 7-point scales (1 indicating strong disagreement and 7 indicating strong agreement). Internal consistency of items was assessed with the Cronbach α, and the Spearman-Brown reliability adjustment was used to calculate reliability for 2 to 5 raters. <h3>Results</h3> A total of 322 participants (202 female participants [62.7%]; 83 aged 40-49 years [25.8%]) rated the survey items (on a 7-point scale). All 11 items were rated as easy to understand (with a mean [SD] ranging from 5.2 [1.38] for the alignment of values item to 6.3 [0.87] for the evidence item) and easy to apply (with a mean [SD] ranging from 4.8 [1.49] for the alignment of values item to 6.1 [1.07] for the evidence item). Participants provided favorable feedback on the tool’s instructions, which were considered clear (mean [SD], 5.8 [1.06]), helpful (mean [SD], 5.9 [1.00]), and complete (mean [SD], 5.8 [1.11]). Participants considered the tool easy to use (mean [SD], 5.4 [1.32]) and thought that it added value to the guideline enterprise (mean [SD], 5.9 [1.13]). Internal consistency of the items was high (Cronbach α = 0.94). Positive correlations were found between the overall AGREE-REX score and the implementability score (<i>r</i> = 0.81) and the clinical credibility score (<i>r</i> = 0.76). <h3>Conclusions and Relevance</h3> This cross-sectional study found that the AGREE-REX tool can be useful in evaluating CPG recommendations, differentiating among them, and identifying those that are clinically credible and implementable for practicing health professionals and decision makers who use recommendations to inform clinical policy.
Clinical trials navigator: Patient-centered access to clinical trials.
Authors: Caroline M. Hamm, Krista Naccarato, Stephen Sundquist, Suzana Kovacevic, Youshaa El-Abed, Janet Dancey
Journal: Journal of Clinical Oncology (2020)

e14024 Background: Despite recommendations from premier institutions such as NCCN that all cancer patients should be entered on clinical trials, only 3 – 5 % of adult cancer patients are enrolled on clinical trials in North America. The reason for this is multi-factorial and includes poor trial design, inappropriate endpoints, inappropriate inclusion/exclusion factors, attitudes about trial participation held by patient and/or treating physician and lack of trial availability. Methods: To address issues of trial availability, in March 2019, we initiated a novel service to help Canadian patients find clinical trial options. The service compares patient demographic and health status information provided against potential opportunities sourced using clinicaltrials.gov and Canadian clinical trials websites. A report presenting outcomes of CTN review is developed for the requesting patient or physician. An interview is provided for the self-referring patient by supporting physicians. Results: To date 96 patients have used this service. Most (94%) were stage IV or refractory/ relapsed. Smaller disease sites represented 23% of our patient population (brain, sarcoma, pancreas). Our turn-around-time from request of services to delivery of report to patient or physician improved over time and is currently 24 hours during the working week. Of those eligible, 25% of patients died before referral, the median time from referral to the CTN to the patient’s death was 109 days (3 – 188 days). Conclusions: Significant interest from both physicians and patients for this service was identified. Strategies are being developed to encourage earlier referrals to clinical trials would improve number of patients entering clinical trials as 25% of our patients. [Table: see text]