tbuckley/cabot-search huggingface dataset:
DaroACT: Darolutamide and enzalutamide effects on physical and neurocognitive function and daily activity in patients with castration-resistant prostate cancer (CRPC).
Authors: Tomasz M. Beer, Neal D. Shore, Alicia K. Morgans, Kerri M. Winters-Stone, Jeffrey Scott Wefel, Jorge A. Ortiz, John A. Reeves, Daniel J. George
Journal: Journal of Clinical Oncology (2020)

TPS5587 Background: The androgen receptor inhibitors (ARIs) apalutamide and enzalutamide (Enza) are approved for the treatment of men with advanced prostate cancer. These ARIs are associated with adverse events (AEs) including fatigue, neurocognitive dysfunction, and falls. Darolutamide (Daro) is a structurally distinct ARI approved by the FDA to treat nonmetastatic CRPC, based on significantly improved metastasis-free survival vs placebo in the ARAMIS Phase III clinical trial. Daro was not associated with a significant increase in AEs beyond that of concomitant androgen deprivation therapy, compared with placebo. DaroAcT is the first prospective trial to compare the effects of Daro to those of Enza on physical and neurocognitive function, and daily physical activity, in men with CRPC. Methods: This randomized, open-label, multicenter, Phase IIb trial (NCT04157088), involving ~20 sites across the US, is open for enrollment. After a lead-in phase of 30 pts treated with Daro alone, approximately 120 pts will be randomized 1:1 to receive Daro (600 mg twice daily) or Enza (160 mg once daily). Eligibility criteria include CRPC (metastatic and non-metastatic); age ≥18 years; Karnofsky performance status ≥80; no prior abiraterone within 6 months of enrollment, and no prior immunotherapy or apalutamide. All patients will continue luteinizing hormone-releasing hormone agonist or antagonist treatment for the duration of the study. The primary endpoint is the proportion of pts with slowed Timed Up and Go (TUG) time during the 24-week period from baseline. Secondary endpoints include the proportion of pts with worsening in short Physical Performance Battery (sPPB), mean change from baseline in daily physical activity, the proportion of pts with a decline in neurocognitive function or worsening of fatigue, and AEs. This study uses objective measures to assess physical function, including TUG and sPPB, measurements of daily activity levels with an accelerometry device for ≥7 days at designated time points, and neurocognitive tests. Fatigue is measured using the Brief Fatigue Inventory. Primary completion is estimated to be December 31, 2022. Clinical trial information: NCT04157088 .
Barriers to accessibility of targeted therapy for breast cancer: A qualitative study in Yerevan, Armenia.
Authors: Darshan Shingala, Jemma Arakelyan, Samvel Bardakhchyan, Gevorg Tamamyan
Journal: Journal of Clinical Oncology (2020)

e13013 Background: The treatment prospects for Human Epidermal Growth Factor Receptor 2 positive (HER2p) breast cancer (BC) patients are continuously evolving, however, BC remains a major public health problem. Multiple therapeutic and biological strategies are already in function, and specifically the anti-HER2 therapy (trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine) remains a mainstream clinically approved treatment method. Implementation of the anti-HER2 therapy has substantially strengthened the prognosis for HER2p patients. This has remarkably improved the 5-year survival rates upto 80% in high-income countries, 60% in middle-income countries and 40% in low-income countries by establishing anti-HER2 therapy. Barriers to anti-HER2p therapies in low- and middle-income countries (LMICs) can be minimized by further instigation and licensing of the bio-similar drugs as a low-cost alternative treatment. Bio-similar drugs will also potentially result in a considerable savings for patients and eventually lessen the burden on the health care systems of LMICs as the usual cancer treatment regimen includes multiple systemic therapies for an extended time period, which are highly expensive. The aim of the study is to identify the barriers to accessibility of targeted therapy for BC, among patients seeking BC treatment in Yerevan, Armenia. Methods: The qualitative study assessed the out-of-pocket (OOP) payment burden among patients and their opinions about the quality of treatment using an interview guide with probe questions, adapted to the Armenian context. The study participants were patients seeking BC treatment at Hematology Center and Mikhaelyan Medical Center. Results: All the study participants were satisfied with the quality of health care and health care providers, however, majority of the study participants paid OOP for the examination, analysis and therapeutic drugs. Most participants were sponsored by family members and stated being financially vulnerable. Conclusions: The study provides evidence for the development and implementation of biosimilar drugs, implementation of mandatory health insurance to increase the access to targeted therapy, enhance collaboration with international funding agencies and strengthen diaspora support.
Safety and clinical activity of combination treatment with regorafenib and milciclib in liver transplant patients with hepatocellular carcinoma recurrence.
Authors: Alessandra Pivetti, Lorenza Di Marco, Laura Bristot, Fabiola Milosa, Rosina Maria Critelli, Nicola De Maria, Fabrizio Di Benedetto, Vaseem Palejwala, Jules Jacob, Kunwar Shailubhai, Erica Villa
Journal: Journal of Clinical Oncology (2020)

e16634 Background: Recurrence of hepatocellular carcinoma after liver transplant (LT-HCC), affects ~40% of patients. As LT-HCC drastically limits therapeutic options, combination of drugs with different mechanism of actions might be an attractive approach. Primary objective of this MiHRCO (Milciclib and Half Regorafenib CO-administration) protocol (87/2019/COMP/MiHRCO) is to evaluate safety and clinical activity of combination of Regorafenib (a tyrosine kinase inhibitor with higher clinical activity in aggressive HCC) with Milciclib (a pan cyclin dependent kinase inhibitor with clinical activities in refractory solid malignancy patients and HCC) in LT-HCC patients. Methods: Seven patients with LT-HCC are enrolled to date. Regorafenib administered at half the prescribed dose (80mg/day) for 3 weeks followed by 1 week Off and milciclib at 100 mg daily for 4 day On/3 day Off. Patients were maintained on this combination regimen until disease progression and/or unacceptable side effects. Primary endpoint was safety and secondary endpoints included progression free survival, time to progression, and clinical benefit rate. Results: This single-arm, single-center operative protocol in LT-HCC patients with extra-hepatic metastasis, not eligible to first line therapy with sorafenib (Todesca P. et al. Hepatology; doi: 10.1002/hep.30588), is currently ongoing. The combination treatment is well-tolerated with manageable toxicities (mostly related with regorafenib), i.e. moderate diarrhea, slight increase of hypertension in previously hypertensive patients and moderate hand and foot syndrome. Patients continuing with therapy are currently in 2 to 10 months of treatment period. All patients are exhibiting stable disease with reduced clinical symptoms. The mean AFP (□-fetoprotein) level (1310±200 ng/ml) at enrollment was reduced by 20% with in the first month of therapy. Importantly, AFP levels in 2 patients, treated for longer period, were reduced by 50%. Conclusions: Regorafenib and milciclib combination was well-tolerated. Most patients showed disease stabilization along with reduction in AFP levels within the first month of therapy. The encouraging clinical activity in difficult-to-treat patients with LT-HCC warrants continuation of this protocol and further evaluation in a larger controlled study. Clinical trial information: 87/2019/COMP/MiHRCO .
Development of an algorithm using natural language processing to identify metastatic breast cancer patients from clinical notes.
Authors: Krishna Kumar Swaminathan, Emma Mendonca, Pranay Mukherjee, Karpagavalli Thirumalai, Rachel Newsome, Babu Narayanan
Journal: Journal of Clinical Oncology (2020)

e14056 Background: Determination of the metastatic status of a patient is important for outcomes research and candidacy for clinical trials. Structured data in EMR may not always capture the metastatic status, and it is useful to extract it automatically from physician notes. Contextual understanding of the notes is important to resolve issues such as a) local vs distal metastasis b) statements involving family history of metastasis or physician instructing the patient to look for certain signs of metastasis c) text indicating suspicion of metastasis or absence of metastasis d) indirect utterances, e.g. cancer has spread to the bone. e) corrections to previous findings. Methods: We used a set of 20138 breast cancer patients from Concerto HealthAI real world oncology dataset that includes data from CancerLinQ Discovery to build &amp; validate the set of NLP algorithms. 5300 sentences from 1500 patients were annotated &amp; algorithms manually validated by data abstractors for 500 patients. The algorithms developed were the following: 1) Classification of a sentence into 3 classes: Distal/Local metastasis, Suspicious &amp; Other 2) Classification of a sentence into 2 classes: Distal or Local 3) Classification of a patient into 2 classes: Distal metastasis or not distal metastasis 4) Multi label classification for detecting sites of metastasis. Sentence level algorithms were built using Deep Learning and patient level aggregation of sentence level prediction was done using ML approaches including temporal features. Pretrained ULMFiT model was fine-tuned with Concerto HealthAI’s corpus for sentence classification tasks. Results: At a sentence level, we obtained an accuracy of 0.85 for the distal/local vs suspicious vs irrelevant model and 0.97 for the distal vs not distal metastasis model. Our patient level metrics are shown in the table. The classes used for sites of metastasis are Brain, Bone, Lung, Liver, Distant Lymph nodes &amp; Unknown sites. Subset accuracy (mean fraction of labels which match ) of 0.93 was obtained on the hold out test set at patient level. Conclusions: Metastatic status &amp; site of metastasis can be reliably extracted automatically from clinical notes using deep learning techniques. This information will be valuable for clinical trial matching, outcomes research and other applications. [Table: see text]
两种联合化疗方案治疗老年复治性痰菌阳性肺结核疗效比较
Authors: 李玉强
Journal: BMJ (2005)

将符合入选标准的84例老年复治性痰菌阳性肺结核患者分为治疗组(44例)和对照组(40例),治疗组采用帕司烟肼与左氧氟沙星联合化疗,对照组采用异烟肼与左氧氟沙星联合化疗,采用全程监督化疗.治疗组完成疗程时痰菌阴转率、Χ线显效率和空洞闭合率均显著高于对照组,不良反应发生率和2年细菌学复发率显著低于对照组,差异均有统计学意义(P＜0.05).证明帕司烟肼与左氧氟沙星组成的方案对老年复治性痰菌阳性肺结核疗效显著并且安全方便。
妊娠合并自发性脾破裂一例
Authors: 孔守芳, 孙选, 解梅林
Journal: BMJ (2010)

患者女,27岁,孕3产1.因停经79 d,突发腹痛5 h,于2009年9月9日入院.患者平素月经规律,末次月经2009年6月22 日.停经35d自测尿妊娠试验阳性,出现恶心、呕吐等早孕反应。
Hepatic arterial infusion (HAI) chemotherapy via the medtronic pump-assessing dose delivery, response rates and toxicity.
Authors: Louise Catherine Connell, Laura Fiedler, Shannan Dickinson, Michele Ly, Kate Harrington, William R. Jarnagin, T. Peter Kingham, Jeffery A. Drebin, Vinod P. Balachandran, Alice C. Wei, Michael Ian D'Angelica, Nancy E. Kemeny
Journal: Journal of Clinical Oncology (2020)

e16007 Background: Due to the termination of the Codman pump, in order to administer hepatic arterial infusion (HAI) chemotherapy, the Medtronic pump has been used with the Codman catheter at MSKCC since 2018. Methods: Retrospective review of patients(pts) receiving HAI therapy via Medtronic pumps. Expected versus actual dose delivery of HAI FUDR, response rates and safety were reviewed. Results: Pts included; unresectable colorectal liver metastases (CRLM) (94 pts), resected CLRM (66 pts) and unresectable intrahepatic cholangiocarcinoma (ICC) (11 pts). Baseline characteristics of the 171 evaluable pts are shown in Table. In 120 pts with mCRC, 51.8% (n = 58) had 10 or more hepatic tumors and 23.2%( n = 26) had 50% or more liver involvement by metastases. 52 out of 171 pts (30.4%) had 100% of the expected FUDR doses by completion of the 3 rd cycle. Another 49.7% (85/171) had greater than or equal to 50% of the expected FUDR dose. 96 pts had measurable disease (unresectable CLRM and ICC subgroups) evaluated by RECIST 1.1 with an MSK radiologist. The partial response for unresectable CRLM pts was 47% (41/87), and 28% (24/87) were stable. The partial response for ICC pts was 22% (2/9), and 33% (3/9) were stable. Conclusions: We evaluated 171 pts who were heavily pretreated and had extensive disease prior to pump placement. Partial response by RECIST 1.1 of 47% was evident in those pts with CRLM and 22% for pts with ICC. Dose delivery of HAI FUDR was compatible with that seen with the Codman pump and no increase in toxicity was noted. An updated analysis with additional evaluable pts will be presented at the meeting. [Table: see text]
Application of two-dimensional and color Doppler ultrasonography and B-blood flow to quickly screen venous diseases of lower extremities in late pregnant women
Authors: Xiu-ping Wang, Shao-peng Xu, Lipeng Lin, Yi-er Guo, Lan Lin
Journal: BMJ (2009)

Objective To evaluate the value of two-dimensional (2D) and color Doppler ultrasonography and B-blood flow (B-flow) in quick screening for venous diseases of the lower extremities in late pregnant women. Methods Sixty late pregnant women excluding other-cause blood vessel diseases were recruited during September 2007 to January 2008 and underwent 2D and color Doppler ultrasonography and B-blood flow examinations for diameter and blood flow velocity of the veins in their both lower extremities during prenatal and postnatal periods to record intravenous condition, activities of the venous valve and venous valvular regurgitation in detail. Results Diameters of the veins in beth lower extremities of the late pregnant women widened significantly during prenatal period, as compared to that in postnatal period [(11.5±1.5) mm vs. (8.4±1.0) mm, t =7.14, P <0.01] and their blood flow velocity slowed down significantly in prenatal period than that in postnatal period [(11.5±4.0) cm/s vs. (29.7±6.9) cm/s, t =-15.74, P <0.01]. Spontaneous enhancement phenomenon could be shown in their veins in 57 of 60 (95%) pregnant women by 2D and color Doppler ultrasonography, but could not be shown by 2D and color Doppler uhrasonography in the poplitel veins in 21 pregnant women (35%) or in the small and great saphenous veins in 39 pregnant women (65%), which should be activated by B-flow. Venous valvular regurgitation occurred in the great saphenous veins and the superficial femoral veins in 24 percent of pregnant women during prenatal period, and small venous valve bag thrombus formed in 20 percent of the superficial femoral veins and 10 percent of the great saphenous veins, but disappeared two weeks after delivery, without formation of pulmonary embolism. Conclusion Tow-dimentional and color Doppler ultrasonography and B-blood flow examinations can be used in late pregnant women to quickly screen for venous diseases in their lower extremities. 

Key words: 
Ultrasonography,Doppler, color;  Pregnant women;  Vein, lower extremity
Use of a real-world data approach to rapidly generate outcomes data following a case study of a novel treatment combination in pancreatic adenocarcinoma.
Authors: Lola Rahib, Karen Chen, Allyson J. Ocean, Changqing Xie, Austin Duffy, Gulam Abbas Manji, Tim F. Greten, Mark Shapiro, Jeff Shrager, William Hoos, Bryan Federowicz, Conan Grant Kinsey
Journal: Journal of Clinical Oncology (2020)

e16735 Background: We use a real-world data approach to report on safety and benefits on metastatic pancreatic cancer pts who were treated with a MEK inhibitor plus hydroxychloroquine (HCQ) after exhausting all other treatment options. MEK inhibition acts on the KRAS pathway, which in turn increases autophagy as a resistance mechanism, furthermore, HCQ inhibits autophagy causing a cytotoxic effect. This combination was shown to diminish tumor volume in xenograft mouse models and a partial response in one heavily pre-treated patients was reported. Methods: XCELSIOR is an IRB approved, patient-centric, real-world data and outcomes registry for developing operational and analytic methods in precision oncology. Searching the XCELSIOR database, we identified 14 pts for whom this regimen had been considered. As part of their participation in XCELSIOR, these patients shared access to their full medical records, which were collected, processed, and abstracted into a 21 CFR 11 compliant database for analysis. We additionally collected de-identified data on 12 pts treated with this combination from five academic centers. Three more patients are expected to start treatment soon. Results: Between March 2018 and January 2020, 15 patients treated with the trametinib/HCQ combination and 3 patients treated with cobimetinib/HCQ were identified in XCELSIOR and five academic institutions. The median age at diagnosis was 64 (range 43-74) and 56% were male. For patients treated with trametinib/HCQ, the median time on treatment was 67 days (range 5-172 days), 11 patients were treated for more than 30 days (median time 97 days). The median PFS for this group was 2.9 months and the median OS was 7.4 months. The clinical benefit rate was 60% for the 10 evaluable patients treated with trametinib/HCQ, 1 patient had a partial response (previously published), 5 had stable disease (for at least 8 weeks) and 4 had progressive disease (physician reported). 2/3 patients treated with cobimetinib/HCQ were on treatment for more than 30 days and all three had progressive disease within 7 weeks. The most common side effects were Grade 1 fatigue and Grade 1/2 rash for both combinations. An additional 3 patients will start treatment soon and will be included in the analysis. Conclusions: Combinatorial MEK and autophagy inhibition was well tolerated in heavily treated metastatic pancreatic cancer patients. Trametinib/HCQ demonstrates some clinical benefit for this group. We demonstrate the feasibility of utilizing real-world data in precision oncology. Clinical trial information: NCT03793088 .
Surgical wound dehiscence in dermatologic surgery.
Authors: Tanner Harding, Jennifer Seyffert, Brittany Maner, Nathan Bibliowicz, Asmi Sanghvi, Shawn Camner, Martin Yungmann, James A. Solomon
Journal: Journal of Clinical Oncology (2020)

e22101 Background: Surgical wound dehiscence (SWD) describes separation of wound edges due to mechanical failure of a healing wound. The rate of SWD following dermatology office-based surgery and factors associated with its occurrence are poorly characterized in the current literature. This study aims to elucidate factors contributing to SWD following cutaneous excisions of malignant and non-malignant through a novel data mining methodology. The utility of this methodology in quality assurance and risk management applications will be concomitantly explored. Methods: An electronic query directed at the electronic medical record (EMR) database of a large national dermatology practice employing over 400 providers yielded 22,548 instances of cutaneous excision meeting inclusion criteria between 1 January 2018 and 9 September 2019. To control for confounding, procedures positive for SWD were randomly matched in 1:4 ratio with procedures negative for SWD on the basis of sex, age, and precise anatomic location. Procedures were then statistically analyzed to elucidate factors associated with SWD. Results: Of 22,548 procedures analyzed, 123 were positive for wound dehiscence, yielding an incidence of 0.54%. Age ( Χ 2 ( df = 1, N = 615) = 2.49, p = 0.039), smoking history ( Χ 2 ( df = 2, N = 534) = 9.97, p = 0.007), wound location on the distal extremities ( Χ 2 ( df = 1, N = 615) = 9.54, p = 0.002), presence of postoperative infection ( Χ 2 ( df = 1, N = 600) = 34.87, p &lt; 0.001), and presence of postoperative bleeding ( Χ 2 ( df = 1, N = 600) = 62.73, p &lt; 0.001) are all significantly associated with SWD. A wound positive for postoperative infection or bleeding has 14.48 times the odds of being positive for SWD (95% CI: 4.62 - 45.21). A wound positive for postoperative bleeding has 20.15 times the odds of being positive for SWD (95% CI: 7.42 – 54.73). No significant relationship between SWD and sex, diabetes, or provider type is evident. Conclusions: Age, smoking history, wound location on the distal extremities, and especially other postoperative complications such as bleeding and infection are associated with SWD. There is no association between SWD and sex, diabetes, or provider type. Forthcoming multifactorial, nonlinear, non-time-dependent analysis of variables may allow for the development of a statistical model to provide greater insight into SWD following dermatologic surgery.
血液白细胞计数和分类异常的临床解读
Authors: 王宇
Journal: BMJ (2008)

当我们在临床工作中见到一张血常规化验单时,其中非常重要的一组数据就是白细胞计数和分类.白细胞是循环血液中中性粒细胞、嗜酸性粒细胞、嗜碱性粒细胞、淋巴细胞和单核细胞的总称,均起源于多能造血干细胞.白细胞通过不同方式、不同机制消灭病原体,消除过敏原,参加机体的免疫反应,产生抗体,在机体抵抗病微生物中发挥重要作用。
Personalized neoantigen/cancer testis antigen nanovaccine (PVAC) mobilize specific therapeutic immunity for high-risk resected gastric cancer.
Authors: Qin Liu, Hanqing Qian, Jie Shao, Qiuping Xu, Huizi Sha, Yang Yang, Weifeng Wang, Lixia Yu, Baorui Liu, Jia Wei
Journal: Journal of Clinical Oncology (2020)

4535 Background: 35% of stage IIIB/C Gastric cancer patients will recurrent after D2 gastrectomy within one year. Mutation-derived epitopes (neoantigens) has been demonstrated to induce tumor cell specific immune responses controlling the tumor growth. Nanovaccine can increase antigen presentation efficiency and elicit potent antitumor T cell responses with robust therapeutic efficacy. We hypothesized that vaccination with neoantigens/cancer testis (CT) antigens could expand pre-existing and induce antigen-specific T-cells populations, favouring of tumor control enhancement. Here, we report the first-in-human application of this concept in gastric cancer. Methods: Patient-specific mutation-containing neoantigens were selected on the basis of tumour-specific mutations whole-exome sequencing (WES) and RNA sequencing. Cancer testis antigens were obtained according to immunohistochemical staining and HLA-binding affinity prediction. PVAC is an amphiphiles nanovaccine loaded with multiple personalized neoantigens/cancer testis antigens designed to induce antigen specific T cells and associated antitumor responses. PVAC will be administrated to stage IIIB/IIIC gastric carcinoma after six cycles of adjuvant chemotherapy (S-1/Oxaliplatin or S-1/docetaxel). Each patient received PVAC by subcutaneous injection on Days 1, 4, 8, 15, 22, 43, 64, 85, 169, administrated with the adjuvant montanide ISA 51 VG. Safety, immunogenicity and clinical efficacy will be evaluated. Results: 25 stage IIIB or IIIC gastric cancer patients were enrolled in this study. Mean age was 54.3 years old (range: 34-70), and ECOG performance scores were 0 or 1. Repeated dosing has been well tolerated with mild local discomfort and no DLTs. Three patients were observed grade 2 local skin reactions in the injection sites. No SAEs related to PVAC have been observed. Among median follow up time of 12.6 months (range: 8.5-25.0 months), only two patients had local recurrence at 24.0 months and 10.5 months after surgery, respectivelt. The rest 23 patients remain disease free on study. Neoantigen specific T cell responses have been detected by IFN-γ Elispot from PBMCs. Conclusions: PVAC is a multiple neoantigen/CT antigens nanovaccine that personalizes tumor specific antigens and the individual patient’s capacity to respond. Addition of PVAC may prolong progression-free survival (PFS) after the standard of care chemotherapy. Clinical trial information: ChiCTR1800017319 .