tbuckley/cabot-search huggingface dataset:
Statistical modeling of a novel clinical trial design using neoadjuvant therapy (NAT) to personalize therapy in patients (pts) with triple-negative breast cancer (TNBC).
Authors: Stacy L. Moulder, Roland L. Bassett, Jason B White, Lei Huo, Senthil Damodaran, Bora Lim, Naoto T. Ueno, Rashmi Krishna Murthy, Banu Arun, Vicente Valero, Debu Tripathy, Gabriel N. Hortobagyi, Jennifer Keating Litton, Alastair Mark Thompson, Elizabeth A. Mittendorf, Elizabeth Ravenberg, Lumarie Santiago, Beatriz E Adrada, Rosalind P Candelaria, Gaiane M Rauch
Journal: Journal of Clinical Oncology (2020)

595 Background: 40-50% of pts with TNBC develop pathologic complete response (pCR) with adriamycin/cyclophosphamide (AC)àtaxane (T) NAT; thus, most pts treated in randomized trials (RCTs) adding experimental drugs (ED) to standard NAT do not benefit from trial participation. A personalized trial design that enriches for non-pCR to standard NAT would diminish toxicity from ED in pts who do not need them and enrich ED in high-risk pts that are most likely to benefit. Methods: ARTEMIS (NCT02276443) is a non-randomized trial to study personalization of NAT in TNBC. Tumor biopsies were performed pre-NAT and volumetric change by ultrasound (VCU) after 4 cycles of AC (or upon clinical progression) assessed response. Pts with sensitive TNBC (VCU &gt;=70% after AC) had T as the second phase of NAT. Pts with &lt;70% VCU were offered phase II trials. pCR was assessed at surgical resection. 273 pts had available pCR status and 222 had complete data to generate a model predictive of response using multivariate logistic regression with common clinical factors. Data was randomly divided into training (n=111) and validation (n=111) sets. Results: 85 pts (38%) had pCR and VCU after AC x 4 was the strongest predictor of pCR. Other factors significant on multivariate analysis and included in the model were T stage (T1-4), stromal TIL, Ki67 and PD-L1. When applied to the validation data set, the accuracy of this model for predicting pCR was 76.6%, sensitivity 78.6% and specificity 75.4%. The PPV was 66.0% and the NPV was 85.2% with a ROC curve AUC of 82.4%. Using these data, ED exposure (table) was estimated for the ARTEMIS study design vs a 1:1 or a 2:1 RCT design (with an estimated pCR in control arm=40%), with a demonstrated benefit for personalization. Conclusions: This modeling indicates that personalization of NAT trials has the potential to enrich ED exposure for non-responsive disease as well as diminish ED exposure in pts likely to achieve pCR with standard NAT. Improved prediction of pCR would further enhance personalized trial design. Clinical trial information: NCT02276443 . [Table: see text]
The landscape of gene fusions and the correlation with immunotherapy biomarkers in Chinese patients with advanced solid tumor.
Authors: Wenshuai Liu, Yifan Zhou, Bei Zhang, Yuezong Bai, Yueqi Wang
Journal: Journal of Clinical Oncology (2020)

e15039 Background: Due to the U.S. Food and Drug Administration approval of larotrectinib, a tumor or tissue-agnostic cancer treatment, gene fusions and fusion-driven cancer were identified as indications. Exploration of the gene fusions might be essential in both target therapy and immunotherapy in advanced solid tumor. However, the landscape of gene fusions in Chinese solid tumor patients is poorly reported. Methods: Tissue samples were obtained from 7514 Chinese patients with advanced solid tumor. Genomic alterations were identified via the next generation sequencing (NGS) with a validated commercial 381-cancer-gene panel (panel size over 0.5 MB), including 100 MSI loci. TMB was calculated according to NGS results. Statistical analysis was performed by Fisher exact test using R 3.6.1. Results: There were 162 pathologic or very like pathologic gene fusions observed in 249 (3.31%) patients, covering 30 cancer types. Top frequent fusion genes were ALK (93), RET (32), FGFR2 (26), FGFR3 (13), ROS1 (10), TMPRSS2 (10) and NTRK1 (9). Their main partner genes were EML4 (66/ 93), KIF5B (15/32), BICC1 (5/26), TACC3 (13/13), CD47 (3/10), ERG (9/10) and TPM3 (5/9), respectively. Mostly, only one fusion was detected in one patient. Three patients harbored 3 gene fusions and 35 patients harbored 2 gene fusions, among which 21 patients were observed harboring both fusion and its reciprocal fusion. In the group of patients harboring gene fusions, the prevalence of MSI-H was 4.0% (10/ 249). Especially, the prevalence was significant high (41.2%, 7/ 17) in colorectal cancer patients (P &lt; 0.001). In MSI-H colorectal cancer patients, 4 carried NTRK1 fusions, 2 RET fusions and 1 ALK fusion. And all of them had high tumor mutation burden (TMB). As another immunotherapy response predictor, TMB was low in most solid tumor patients in this study, except for the patients harboring gene fusions involving NTRK1, NTRK2 or STK11, whose TMB-H proportion were 67%, 50% and 33%, respectively. Conclusions: Gene fusions might be associated with MSI-H. In colorectal cancer patients, gene fusions involved either NTRK1 or NTRK2 might be associated with TMB-H, which revealed a potential biomarker for both target and immunotherapy.
COVID-19: 10 things I wished I’d known some months ago
Authors: Peter Pickkers, Hans van der Hoeven, Giuseppe Citerio
Journal: Intensive Care Medicine (2020)

The COVID-19 pandemic is ongoing and spreading, affecting individuals in over 200 countries now.While COVID-19-related articles are being published every day, including guidelines of optimal clinical management [1], there are several practical issues that we wished we had known earlier.This viewpoint addresses 10 points that may be of interest both the logistics, as well as actual clinical care of critically ill COVID-19 patients.We stay away from items that are self-evident and will not address aspects of treatment that are explicitly described elsewhere [1].
Endoscopic Findings in Patients Infected With 2019 Novel Coronavirus in Lombardy, Italy
Authors: Sara Massironi, Chiara Viganò, Lorenzo Dioscoridi, Elisabetta Filippi, Michela Pagliarulo, Guido Manfredi, Clara Benedetta Conti, Clementina Signorelli, Alessandro Ettore Redaelli, Giulia Bonato, Elena Iiritano, Roberto Frego, Nicola Zucchini, Marco Ungari, Marianna Pedaci, Francesca Bono, Camillo Di Bella, Elisabetta Buscarini, Massimiliano Mutignani, Roberto Penagini, Marco Emilio Dinelli, Pietro Invernizzi
Journal: Clinical Gastroenterology and Hepatology (2020)
肠系膜血管周围上皮样细胞瘤一例
Authors: 刘京礼, 丛振杰
Journal: BMJ (2010)

患者女,48岁.发现下腹部包块3个月于2008年3月19日入院.无腹痛腹胀,无恶心呕吐,无发热,无血便.自发病以来饮食睡眠好,无头晕乏力,无胸闷憋气,大小便正常,体重无下降,未采取任何治疗.入院体检:腹软,未见胃肠型及蠕动波,腹肌软,下腹部可扪及一包块,橘子大小,表面光滑,质韧,深压痛,活动度小.全腹无反跳痛,肝脾肋下未触及,无移动性浊音,肠鸣音正常。
Optimization of two-way referral system in Shanghai Changning district
Authors: Wei Yan, Ping Jiang, Chunrong Hong, Lihua Qiao, Donglei Miao, Qiong Wu
Journal: BMJ (2017)

Based on the summary of the implementation of two-way referral system in Changning district, the article describes the system construction, path design, information platform support and achievements, taking into account of general practitioners, specialist and patients. Through a series of reforms, a two-way referral service and its operation mechanism with the local characteristics has been established in Changning district, which guides the first contact care at community and two-way referral as a rational medical service system.


Key words: 
Patient transfer; General practitioner
胸膜活检在胸腔积液诊断中的价值
Authors: 陈亚利, 杨梅, 霍敏琴
Journal: BMJ (2004)

胸膜活检在渗出性胸腔积液的病因诊断中起着非常重要的作用.使用改良Cope胸膜活检针可大大提高活检成功率和阳性率.我科对自1998年2月～2003年2月收治的103例渗出性胸腔积液患者常规行胸膜活检,其诊断阳性率高达89.32%。
Using consistent terms in precision medicine to eliminate patient confusion.
Authors: Nikki A. Martin, Sue J. Friedman, Claire Saxton, Ronit Yarden, Stacie Lindsey, Erica Kuhn, Janine Guglielmino, Reese Garcia, Cassadie Moravek, Deborah A. Zajchowski, Andrea K. Miyahira, Denisse Montoya, Christine Verini, Janelle Schrag, Victor Gonzalez, Gillian Hooker, Cynthia Bens, Beth Davison, Marcia K. Horn
Journal: Journal of Clinical Oncology (2020)

e24164 Background: Biomarker testing has advanced precision medicine in cancer. However, not all eligible patients benefit from biomarker-driven therapies due to suboptimal testing rates. A working group of 20 patient advocacy groups representing solid/hematologic malignancies, three professional societies, and 18 pharmaceutical and diagnostics companies identified patient confusion inconsistent testing terms as a possible contributing factor to biomarker testing underutilization. The group aimed to address patients’ confusion by identifying and adopting consistent, plain language terms for biomarker and germline genetic testing that are applicable across cancer types. Methods: Following a stakeholder roundtable discussion on barriers to precision medicine, working group members participated in interviews on their goals for consistent testing terminology for their constituents. We then conducted a framework analysis covering five themes: available testing by cancer type; purpose of test; biospecimen source; terms used in patient education; and preferred plain language term. Working group members were surveyed on preferences for germline testing terminology and also deployed a preliminary patient survey to their constituents to gain insight on preferences for germline testing terms. Results: Interviews, framework analysis, and surveys revealed notable differences across cancer communities. We identified at least 33 different terms related to biomarker, genetic and genomic testing being used in patient education and clinical care among the different cancer communities and stakeholders. Terminology was complicated by the variety of testing modalities and gene mutations tested for across cancers. Following multiple discussions, working group members agreed on two umbrella terms to distinguish between somatic and germline testing with additional context for specific cancer communities. “Biomarker testing” was selected as the somatic testing term. “Genetic testing for an inherited mutation” and “genetic testing for inherited cancer risk” were selected as preferred germline testing terms. Conclusions: Our findings highlight the disparate testing terminology landscape and the need for consistent terms to reduce patient confusion, improve communication, facilitate shared decision-making and assure concordance in policy development.
Effectiveness of a medical student-led, advanced care planning intervention in an inpatient cancer population.
Authors: Linda Nguyen, Shelly S. Lo, William Adams, Paul J. Hutchison
Journal: Journal of Clinical Oncology (2020)

e24010 Background: In an effort to provide patients with care that aligns with their values and goals, patients are encouraged to complete advance directives (ADs). While research has shown the benefits of advanced care planning (ACP) sessions, few studies have examined the thematic content of ACP discussions in an inpatient hematology or oncology population. Methods: We enrolled patients admitted to the hematology and oncology unit of an academic medical center who had never completed a power-of-attorney for healthcare form. One medical student 1) helped patients complete a power-of-attorney for healthcare form and 2) performed semi-structured interviews that explored patient's values, beliefs about end-of-life care, and preferences for medical treatments. Interviews were audio-recorded, transcribed, and analyzed through thematic analysis. Subjects completed pre- and post- surveys assessing their knowledge and attitudes about ACP. Results: All 48 patients enrolled in the study completed an advance directive. There was no significant change between pre- and post- intervention surveys evaluating patients’ trust in their physicians or family members to choose the right treatments for them in a life-threatening situation. Similarly, there was no change in patients’ comfort level discussing advance care planning after the interview. 79.2% of patients agreed or strongly agreed that they would recommend this ACP conversation to family and friends. 35.5% of patients agreed or strongly agreed that having this ACP conversation made them anxious. In the qualitative arm of the study, analysis suggests that cancer patients are willing to undergo further treatment unless it burdens their loved ones or interferes with quality time spent with family and friends. Motivating factors for patients included their spirituality and ability to fulfill a responsibility in a defined role. Conclusions: An ACP intervention performed by a medical student can increase the number of advance directives among patients admitted to inpatient hematology and oncology units. While this intervention may be anxiety-provoking for patients, it can illuminate the relative value patients place on the quality of their life versus their longevity.
Intravenous thrombolysis for acute ischemic stroke: analysis of 22 cases
Authors: Kai Li, Tao Gong, Fang Liu, Ai-zhen Sheng, Hai-bo Chen
Journal: BMJ (2012)

We reviewed medical data of 22 patients receiving intravenous thrombolysis therapy for acute isehemic stroke and evaluated our efforts of promoting intravenous thrombolysis for acute ischemic stroke.The mean in-hospital delay was 107 minutes.The most common reason was waiting for the results of laboratory tests.Only 6 cases received a standard dose of recombinant tissue plasminogen activator (rtPA) at 0.9 mg/kg.Only one patient had asymptomatic intracranial hemorrhage.No symptomatic hemorrhage occurred.Intravenous thrombolysis for ischemic stroke had excellent safety profile.Intravenous thrombolysis for ischemic stroke should be promoted under the guidance of standardized protocol according to the national guideline.

Key words: 
Cerebrovascular accident;  Drug therapy
Breast cancer, placing drug interactions in the spotlight: Is polypharmacy the cause of everything?
Authors: José Alberto Domínguez-Alonso, David Conde-Estévez, Maria Pi-Figueras, Sonia Servitja, Ana Digón, Joan Albanell, Ignacio Tusquets
Journal: Journal of Clinical Oncology (2020)

e24027 Background: Breast cancer is the most prevalent and lethal cancer among women. Forty one percent of cases occur in people ≥ 65 years. Decision on cancer treatment is particularly challenging among this group of age given its comorbidities and polypharmacy (PP). The main objectives are the analysis of potential drug-drug interactions (PDDI) in elderly breast cancer patients between daily medications and oncospecific therapy and their probable associations with age, BMI, Mini Nutritional Assessment (MNA), frailty and PP and the adverse effects during oncospecific treatment. Methods: A cohort of 77 patients ≥ 70 years with breast cancer underwent a Comprehensive Geriatric Assessment (CGA) by a Geriatrist at a university hospital. Baseline characteristics of the patients, demographical data, cancer stage, and oncospecific and daily treatments, as well as the complications and derived adverse effects were retrospectively collected using electronic medical records. Moreover, frailty categorization, daily medication number, comorbidities, Lawton and Barthel Index, malnutrition, MNA, BMI were prospectively collected using CGA report. PDDI between daily and oncospecific treatments were analyzed. Results: The median age of patients was 85 years (range 72-95). The median number of daily medications at CGA was 6 drugs (range 0-22) and most of the patients had PP at CGA and during oncospecific treatment (73% and 91%, respectively). Out of 719 PDDI, 530 (74%) were moderate ( r 2 = 0.72) and the median number of drugs during oncospecific treatment ( r 2 = 0.73) was 9 (range 3-26). Overall, by using Kruskal Wallis, 59 patients (77%) had any adverse effects statistically associated with frailty categorization and MNA ( p &lt; 0.05). Furthermore, there was a tendency with oncospecific treatment, BMI and age ( p = 0.098, 0.089 and 0.062, respectively). The distribution of major, moderate and minor as well as total PDDI was statistically associated with PP at CGA and during oncospecific treatment ( p &lt; 0.05). Conclusions: CGA should be applied in oncology elderly patients not only to assess clinical outcomes and categorize them in each frailty group but also to analyze PDDI by using specific web databases, thereby improving PP, PDDI and economic costs.
Association between tamoxifen and cataract risk in breast cancer patients: Analysis of a national health insurance database.
Authors: Cheng-wei Chou, Ching-Heng Lin, Chieh-Lin Teng, Yuh-Pyng Sher
Journal: Journal of Clinical Oncology (2020)

e24072 Background: Tamoxifen is often used for hormone-positive breast cancer. Recent trials suggested that ten years of tamoxifen use improves recurrence rate and death. Ocular side effects and cataracts were reported in previous trials. We revealed the risk of cataracts from real-world data of the Taiwan national health insurance research database. Methods: We retrieved data from the Taiwan National health insurance research database. Female breast cancer patients from 2000-2005 were enrolled in this study. Patients receiving cataract surgery were enrolled and matched with non-cataract surgery patients for comparison in the analysis. Age, cumulative days, chemotherapy, and the time interval between breast cancer and index date were included and as controlled variables. Results: Among 23,957 female breast cancer patients, a total of 1,578 patients receiving cataract surgery were enrolled and matched with patients without cataract surgery until the end of 2013. Age in patients undergoing cataract surgery group was significantly higher than the non-surgery group (59.9 and 58.3, respectively, P &lt; 0.001). Multiple regression analyses showed an adjusted odds ratio of 1.02 (95% CI:1.01-1.03, P&lt; 0.001). However, more prolonged exposure of tamoxifen (≧3 years) also had a higher risk of cataract development requiring surgery (adjusted odds ratio=1.32, 95% CI: 1.03–1.70, P = 0.030). Conclusions: Besides age, there is a significantly higher risk of cataract development requiring surgery among female breast cancer patients with long term tamoxifen use. Information from this study may provide further clinical surveillance efforts in cancer survivors. [Table: see text]
早期识别危重症:急性意识障碍
Authors: 吴东, 陈嘉林
Journal: BMJ (2011)

意识障碍(disturbance of consciousness)是各种致病因素造成的中枢神经系统功能异常,患者因此不能正确认识自身和环境.急性意识障碍是一种临床急症,常常病情危重,需尽快判断,并及时给予针对性处理.近年来,社区疾病谱已发生明显变化,糖尿病、脑血管病以及慢性肝肾疾病不断增多,急性意识障碍可能是这些疾病的并发症,甚至是首发表现.另一方面,人们生活方式较以往也有所不同,酗酒、吸毒等不良现象时有所见.这些行为也可能造成意识障碍,严重时甚至威胁生命.因此,全科医生不仅要管理病情相对稳定的慢性疾病,也要学会诊治急性意识障碍这样的危重患者。
Nerve block for management of early and postherpetic neuralgia in patients with herpes zoster
Authors: Liping Song, Hui Li
Journal: BMJ (2014)

Objective
To assess the application of nerve block in management of early and post-herpetic neuralgia (PHN) in patients with herpes zoster.


Methods
Seventy three patients with herpes zoster were enrolled, the course of disease was within 15 d and the numeric rating scale (NRS) scores were ≥6. The course of disease was ≤7 d in 37 patients (group Ⅰ), the course was >7 d and <15 d in 36 patients (groupⅡ). After the conventional therapy, all the patients were treated with nerve block.The cervical, thoracic, lumbar paravertebral nerve blocks were performed by injecting 5 ml lidocaine in the concentrations of 0.40%, 0.40%, 0.80% respectively, with 0.25 mg vitamin B12 and 0.5 mg dexamethasone.For the nerve plexus and nerve branch blockages, the concentration of lidocaine was 1.00%, with 0.50 mg vitamin B12 and 2.0 mg dexamethasone, the dosage varied depending on the infection sites.Furthermore, 40 ml lidocaine with a concentration of 0.25% was used for the local infiltration.The NRS scores were documented before and after the treatment, and the differences in cure rate, effective rate and frequency of treatment were compared between groupⅠand groupⅡ.


Results
The scores of NRS decreased significantly in two groups after the treatment of nerve block, at d3 after the treatment, the score of NRS in group Ⅰwas reduced from 7.37±1.43 to 0.92±0.40(t=27.30, P<0.01), and the score of NRS in group Ⅱ was reduced from 7.16±1.41 to 0.75±0.39(t=29.62, P<0.01). There were no significant differences in cure rate, effective rate and frequency of treatment between two groups.The NRS scores of all patients were <3 one month after treatment.


Conclusion
Nerve block has a satisfactory efficacy in treatment of acute herpes zoster, it can also effectively prevent the occurrence of postherpetic neuralgia.


Key words: 
Herpes zoster; Neuralgia, postherpetic; Nerve block; Time management
Hyperthermia combined with nanoparticles to enhance cytotoxic effects of fresh human soft tissue sarcoma.
Authors: Shailaja KS Raj, Shailaja KS Raj, Pierre Triozzi, Stephanie Staley, Cynthia Emory, Scott Wilson, Perry Shen, Edward Allen Levine, Paul David Savage, Nicole Levi-Polychenko
Journal: Journal of Clinical Oncology (2020)

e23570 Background: Sarcomas represent 1% of all adult cancers and 20% of all pediatric cancers worldwide.Sarcomas are heterogeneous with more than 50 histologic subtypes involving the mesenchyme including bones, muscle, fat, blood vessels, and nerves. Patients with high-risk localized or advanced disease are treated with the combination of neoadjuvant or adjuvant chemotherapy, radiation, and surgical resection have all failed to substantially improve overall survival (OS).4 Novel treatments are desperately needed in the management of soft tissue sarcoma. Thermal ablation of sarcoma may offer a novel method for eradicating the disease. Polymer based nanoparticles that can be stimulated with light to generate heat (photothermal nanoparticles) have been developed previously and used to induce. The goal of the current work is to utilize these nanoparticles for selected ablation of sarcoma. Methods: Polymer nanoparticles were first prepared in the in our lab through the synthesis of 2‐ethylhexyl cyclopentadithiophene 2,1,3‐benzoselenadiazole (PCPDTBSe). Nanoparticles of this polymer were prepared using an oil-water emulsion technique, with FITC labeled polyethylene glycol as the stabilizing agent, to create an aqueous suspension. The nanoparticles were characterized for their size and ability to generate heat when stimulated with 800 nm laser light (180J/cm2). Fresh Soft tissue sarcoma samples are obtained through informed consent and approval of the institutional IRB. Nanoparticles were injected into sarcoma in a volume of 100ul, at a concentration of 250ug/ml. The tissues were then exposed to the laser source to generate heat. Controls included the injection of the sarcoma with the nanoparticles and no laser exposure, as well as the injection of water, plus laser exposure. Results: Sarcomas vary in their ability to take up and response to nanoparticles. We have found that liposarcoma samples are extremely leaky and do not hold the injection of nanoparticles, which leach out of the tumor. Conclusions: Future directions include studies that would involve targeted, immunotherapy and chemotherapy given with nanoparticles that facilitate combinatory and unique individual cytotoxic effects of the soft tissue sarcoma subtypes.
Progress on low-dose rituximab for systemic lupus erythematosus
Authors: Junxia Wang
Journal: BMJ (2018)

As a targeted immunosuppressive drug, rituximab is commonly used in the treatment of lymphoma.Recently, its efficacy in the treatment of rheumatic diseases has been concerned.However, studies have found that the dosage of rituximab for systemic lupus erythematosis (SLE) simply followed that for B-cell lymphoma may lead to increased infection risk. This article reviews the clinical application of low-dose rituximab in treatment of SLE with refractory thrombocytopenia, thrombotic thrombocytopenic purpura, lupus nephritis or neuropsychiatric lupus, which suggests that the low-dose rituximab has achieved satisfactory efficacy with good safety and tolerability.


Key words: 
Lupus erythematosus, systemic; Rituximab