tbuckley/cabot-search huggingface dataset:
Efficacy and toxicity of extending bone modifying agents beyond two years for bone metastases in breast or castrate-resistant prostate cancer patients: A systematic review.
Authors: Terry L. Ng, Megan M. Tu, Mohammed FK Ibrahim, Bassam Mohammed Basulaiman, Sharon McGee, Amirrtha Srikanthan, Ricardo Fernandes, Lisa Vandermeer, Carol Stober, Marta Sienkiewicz, Ahwon Jeong, Deanna Saunders, Arif Ali Awan, Brian Hutton, Mark J. Clemons
Journal: Journal of Clinical Oncology (2020)

e24083 Background: Randomized clinical trials evaluated bone modifying agents (BMAs) such as bisphosphonates and denosumab for bone metastases for 1-2 years in duration even though BMA therapy is commonly administered for much longer. A systematic review on the risk-benefit of continuing BMAs for longer than 2 years in breast cancer or castrate-resistant prostate cancer was conducted. Methods: Medline, Embase and Cochrane Register of Controlled Trials were searched (1970 - February 2019) for randomized studies, observational studies, and case series reporting on BMA efficacy and toxicity beyond 2 years. Efficacy was assessed by skeletal-related event (SRE) rates and quality of life metrics. Toxicity was assessed by rates of osteonecrosis of the jaw (ONJ), renal impairment, hypocalcemia, and atypical femoral fractures (AFF). Results: Of 2107 citations, 64 studies were identified. A total of 3 prospective and 9 retrospective studies were eligible. Data beyond 2 years was limited to subgroup analyses in all studies. Three studies [zoledronate (ZOL) (n = 481), pamidronate (PAM) (n = 87), PAM-ZOL (n = 43) ibandronate (n = 30)] reported on SRE-related endpoints. Only one study reported SRE rates based on duration of BMA exposure and showed reduced SRE rates from 27.6% (0-24 months) to 15.5% ( &gt; 24 months) over time. None reported on quality of life. All 12 studies [denosumab (n = 948), ZOL (n = 1036), PAM (n = 163), PAM-ZOL (n = 522), ibandronate (n = 118)] reported on at least one toxicity outcome. Data from 7 bisphosphonate studies (n = 1077) and 1 denosumab study (n = 948) reported on ONJ incidence. In 3 studies (n = 67, n = 221, n = 948), ONJ incidence ranged from 1-4% in the first 2 years and from 3.8-18% beyond 2 years. In another study (n = 252), the cumulative hazard of ONJ was 0% (1% ZOL), 3% (7% ZOL), 7% (21% ZOL) and 11% (21% ZOL) at 12, 24, 36, and 48 months, respectively (p = 0.005); 4 remaining studies reported 1 (n = 181), 3 (n = 57), 7 (n = 99) and 2 (n = 200) cases of ONJ, all after 24 months. Incidence of clinically significant hypocalcemia ranged from 1-2%. Incidence of severe renal function decline was ≤ 3%. AFF occurred in two subjects in one of two studies after 37 and 79 months of BMA exposure. Conclusions: Although the evidence informing the use of BMA is heterogeneous and based on retrospective analysis, BMA exposure beyond 2 years is associated with reduced SRE risk and increased ONJ incidence. Prospective randomized studies addressing the use of BMA for more than 2 years is needed with greater emphasis on quality of life.
Clinical analyses of six Langerhans cell neoplasms
Authors: Xiang-lian Wang, Guo-min Wang, Mei-na Fu
Journal: BMJ (2012)

To explore the clinical features,diagnosis and treatment of Langerhans cell neoplasms.The data of 6 patients with Langerhans cell neoplasms was analyzed retrospectively.There were Langerhans cell histiocytosis (LCH,n =5) and Langerhans cell sarcoma ( LCS,n =1 ).Among 5 LCH patients,the involved organs included waist,back,scalp,inguinal lymph nodes,parotid gland and left femur.And the symptoms were fever,splenohepatomegalia and destruction of bone.Three patients received surgery,1 had radiotherapy and 1 was discharged without treatment.The follow-up period was 34 - 138 months.Two patients had no relapse,the contra-lateral parotid gland became involved later in another and several organs were involved in other patients.One patient was lost to follow-up.Left occiput of another LCS was involved and both surgery and radiotherapy were administered.Over a follow-up period of 41 months,there was no relapse.Either surgery or radiotherapy is indicated for this rare disease when a single organ is involved.And chemotherapy is administered for the involvement of multiple organs.The patients should be treated individually.

Key words: 
Langerhans cell neoplasms;  Clinical protocols
Identifying pan-cancer transcriptomic determinants of perineural and lymphovascular invasion using machine learning.
Authors: Jimmy Guo, Hannah I. Hoffman, Peter G Hwang, Daniel Y Kim, Mohammed Alshalalfa, Brandon Arvin Virgil Mahal, Theodore S. Hong, William L. Hwang
Journal: Journal of Clinical Oncology (2020)

3621 Background: Tumor invasion of nerves, blood vessels, and lymphatics are a primary means of local recurrence and escape from the local microenvironment, resulting in metastases and poor clinical outcomes. However, the genetic drivers that are most pertinent to these malignant processes are not well understood, and few therapeutics successfully target perineural invasion (PNI) and lympho-vascular invasion (LVI). Identifying genetic drivers and biomarkers can be valuable for therapeutic targeting and prognostication. Methods: We analyzed surgical pathology reports and bulk RNA-seq data of 1,624 patients across 12 cancer types from The Cancer Genome Atlas (TCGA). Differential gene expression analysis between patients with and without PNI/LVI was performed using DEseq2 in Python while adjusting for age, sex, race, and cancer type. Genes with an adjusted p-value &lt; 0.001 were then used to derive parsimonious signatures using random forest classifier and recursive feature selection algorithms. Results: To assess whether these invasive histological phenotypes have clinical ramifications, we examined outcomes data and found that patients with PNI or LVI have reduced overall (OS) and disease-free survival (DFS) ( p &lt; 0.05) relative to those without. In addition, patients with both PNI and LVI have the lowest DFS from our pan-cancer analysis, suggesting that each may have non-redundant contributions to poor outcomes. From the differential gene expression analysis, we identified a set of 621 and 606 genes that were highly associated with PNI and LVI, respectively (p adj &lt; 0.001). Many of these genes such as TEKT5 (p adj = 3.18 x 10 −64 ), which is canonically associated with ciliary and flagellar microtubules, and SCRIB (p adj = 1.60 x 10 −21 ), which helps establish apico-basal cell polarity, have not been described previously in relevance to PNI and LVI, and warrant further scientific and clinical investigation. These genes were ultimately condensed into a signature that optimizes for both model simplicity and goodness of fit with up to 90% accuracy as determined by trials on both a logistic regression and neural network model. Conclusions: We concluded from a pan-cancer analysis that PNI and LVI are associated with poor outcomes, and we were able to robustly identify sets of genes that characterize each invasive mechanism for further functional investigation.
Integrating touchscreen-based geriatric assessment and frailty screening for adults with acute myelogenous leukemia to drive personalized treatment decisions.
Authors: Debra Wujcik, Nikolaos Papadantonakis, Sarah Allison Wall, Margaret T. Kasner, OMER HASSAN JAMY, William Dudley, Stacey A. Ingram, Valerie Lawhon, UI Son, Matthew Dudley
Journal: Journal of Clinical Oncology (2020)

e24030 Background: AML is a disease of older adults, with median age of 68 years at presentation. NCCN guidelines suggest comprehensive geriatric assessments (GA) be included in clinical practice to guide treatment decisions. Utility of GA in older AML patients in a real-world environment is not yet established. We tested the feasibility of using a modified GA (mGA), administered by patient self-report on a touchscreen computer, real-time use and utility by clinicians and the correlation of mGA results on treatment decision-making. Methods: Sixty-two patients were recruited from three sites to complete a tablet-based mGA screening at a treatment decision-making time point. The mGA consists of the Frailty Index (FI) that includes four domains: age, activities of daily living, instrumental ADLs, and comorbidities. Falls within the past 6 months and patient reported health interference with function are also assessed. Results are displayed for the clinician to inform the treatment discussion. Results: Participants were mean age 73 years (range 61-88), 63% male, and 90% white. Frailty Index result was 32% fit, 40% intermediate, and 28% frail. Providers were asked the fit/frailty status prior to seeing the results of the mGA. Of 53 provider responses, there was 57% (n=30) provider concordance with the mGA result; 9% (n=5) said fit when mGA said intermediate and 17% (n=9) said intermediate when mGA said frail. When asked their goals of care, nearly all (n=60, 97%) patients agreed with the statement “my cancer is curable”, yet 30% (n=19) disagreed the treatment goal was to get rid of all the cancer. Nearly half (n=30) indicated they want to make treatment decisions together with the provider rather than provider or patient making decision alone. 73% (45/62) of patients were satisfied with the ease of using the survey and took an average 16.3 minutes to complete. Patient self-reported presence/severity of eight symptoms at baseline (see Table). Conclusions: A simple electronic tool may provide valuable insight into patient understanding of disease to better tailor patient-provider discussion and treatment decision-making. Providers overestimated fitness 26% of the time. Final results will be presented to include the outcome at 3 months by Frailty Index. [Table: see text]
The use of plasma proteomic markers to understand the biology of immunotherapy response.
Authors: Arnav Mehta, Marijana Rucevic, Emmett Sprecher, Lina Hultin Rosenberg, David Lieb, Gyulnara G. Kasumova, Michelle S. Kim, Xue Bai, Dennie T. Frederick, Keith Flaherty, Ryan J. Sullivan, Nir Hacohen, Genevieve Marie Boland
Journal: Journal of Clinical Oncology (2020)

10062 Background: Despite recent successes with immune checkpoint blockade (ICB) in melanoma, the prognosis for most patients remains dire. Whereas small fraction of patients are able to achieve disease control, most do not respond or are limited by immune-related toxicities. Robust non-invasive predictors of ICB response have the potential to guide clinical decision and alter management of patients, however, no such predictors currently exist. Methods: We applied a highly-multiplex Proximity Extension Assay to simultaneously detect &gt; 1000 proteins in the plasma of anti-PD-1 treated melanoma patients. Our cohort comprised 116 patients, 66 responders (R) and 50 non-responders (NR). Additional 65 patients comprised a validation cohort with 30 R and 35 NR, and included 50 patients who developed treatment-related toxicities. Plasma samples were collected at baseline, 6-weeks and 6-months after starting the treatment. A subset of patients had single-cell RNA-seq performed on tumor tissue. Group differences and treatment effects were evaluated by linear model with maximum likelihood estimation for model parameters and Benjamini and Hochberg multiple hypothesis correction. Results: At baseline, 6 significantly differentially expressed (DE) proteins were identified between R and NR. Elevated expression of ST2 and IL-6, two key immunoregulatory proteins were found in NR. At 6-weeks, more dynamic changes occurred and 79 significantly DE proteins were identified between R and NR, including proteins implicated in primary or acquired resistance as IL-8, MIA, TNFR1 and potential novel targets as MCP-4/CCL13, ICOSLG and VEGF. Proteomic changes identified at baseline and 6-weeks were more profound at 6-months, and moreover 238 proteins were confirmed significant between R and NR. Importantly, we were able to leverage these differences to build classifiers of R and NR subsets. We compared mRNA expression of DE proteins within the tumor microenvironment by leveraging scRNAseq data from a subset of these patients. Enriched expression of these genes was uncovered in certain myeloid and exhausted T cell subsets, thus shedding insight into the potential role of these cell subsets in ICB response. Conclusions: Plasma proteomic profiling of anti-PD1 treated patients identified important tumor and immune changes associated with response. Non-invasive means discovery of circulatory protein biomarkers may predict sensitivity to immunotherapy and uncover biological insights underlying primary resistance.
Real-world clinical outcomes in avelumab-treated patients (pts) in the United States (U.S.) from SPEAR-Merkel: Study informing treatment pathway decisions in Merkel cell carcinoma (MCC).
Authors: Abhijeet Bhanegaonkar, Frank Xiaoqing Liu, Ruth Kim, Marley Boyd, Nicole Fulcher, Stan Krulewicz, Vijay Kasturi, Charles Lance Cowey
Journal: Journal of Clinical Oncology (2020)

269 Background: MCC is a rare, aggressive disease associated with poor prognosis. Avelumab, a fully human anti–PD-L1 monoclonal antibody, was the first immune checkpoint inhibitor approved by the FDA for the treatment of metastatic MCC (mMCC). In the JAVELIN Merkel 200 trial (Clinical trial information: NCT02155647), avelumab resulted in durable responses and a high objective response rate (ORR) in pts with mMCC. This retrospective descriptive study assessed real-world clinical outcomes in avelumab-treated pts with locally advanced MCC (laMCC) and mMCC in a US community oncology setting. Methods: This study included data on avelumab-treated laMCC and mMCC pts from 1/1/17 to 3/31/19 within The US Oncology Network. Study data were captured through 9/30/19 using structured fields and chart review of iKnowMed electronic healthcare records. Real-world ORR was assessed. Duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan-Meier method. Results: 33 pts initiated treatment with avelumab (laMCC n = 11; mMCC n = 22) and were followed up for a median of 10.9 months (range, 0.5-27.2 months). Median age was 77 years (range, 44-90+ years), 78.8% of pts were male, and the majority (84.8%) of pts were treated in the first-line setting. During treatment, 27.2% of pts had emergency department visits and 39.4% were hospitalized; 1% and 23.1%, respectively, were treatment related. Clinical outcomes are reported in the table. Conclusions: This is the first study to examine pts with laMCC treated with avelumab in a real-world setting. Although the sample population is small, results suggest the clinical benefits in the real world in pts with mMCC treated with avelumab are consistent with benefits reported in the JAVELIN Merkel 200 trial. [Table: see text]
Outcome of metastatic melanoma following immune checkpoint inhibitor treatment by tumor infiltrating lymphocyte of primary cutaneous site.
Authors: Upendra P. Hegde, Aaron N. Holmes, Christina Elizabeth Stevenson, Sophie Masternak, Cucka Bethany
Journal: Journal of Clinical Oncology (2020)

e22005 Background: TIL include antigen specific clonal T cells responding to tumor antigens (TA) in the tumor microenvironment. Biological relevance of TIL at the PCM following ICI treatment of MM is not clear. Since there is overlap of TA between primary and its metastasis, we hypothesized that TIL at PCM site may serve as a biomarker of response to ICI treatment of MM. Methods: We did a retrospective analysis of MM patients (pts.) receiving ICI treatment between 2012 and 2019 following an IRB approved protocol. Response and survival at 12, 24 and 36 months (mths) was correlated with PCM site TIL. Pts. who received at least one dose of ICI for MM were eligible and those with metastasis from unknown PCM, received anti-BRAF treatment or lacked information on TIL at PCM were excluded. Pts. were stratified as group (gr.) A, B and C representing brisk, non-brisk and absent TIL respectively. Responses defined by RECIST criteria (response, no response, stable disease) as well as overall survival calculated from time of initiation of ICI to death from any cause (OS) at 12, 24 and 36 mths was correlated to TIL at PCM. Results: 42 pts. received ICI for MM between 2012-2019 meeting the eligibility criteria. Median age is 68 years (yrs.) (63, 71 and 73 yr. respectively for group A, B and C), 27 male, 15 women. The median thickness of PCM was 3.5, 3.75 and 4.75 mm in group A, B and C respectively. 11 of 14, 9 of 16 and O of 12 pts. responded to ICI while 2, 5, 14 and 1,2, 0 patients showed no response and stable disease respectively. O.S. at 12, 24, and 36 mths. was 12/14, 11/16 and 1/12 pts.; 10/14, 7/16, 0/12 pts. and 8/14, 6/16 and 0/12 pts. respectively in three groups. Conclusions: Brisk and absent TIL correlated with favorable and unfavorable response to ICI treatment of MM while non-brisk TIL showed intermediate outcomes. Larger data set could help validate our findings.
Successful mutational profiling of single circulating epithelial tumor cells (CETCs) from patients with solid cancers for guiding therapy.
Authors: Dorothea Schott, Monika Pizon, Ulrich Pachamnn, Katharina Pachmann
Journal: Journal of Clinical Oncology (2020)

e15527 Background: Circulating epithelial tumor cells (CETCs) are an important link between primary tumors and metastases and provide a readily accessible source of tumor material from patients with solid cancer. Therefore, they are representative for primary and metastatic lesions to evaluate treatment response in real-time and to guide therapeutic modifications. Beyond enumeration, information on mutations is extremely important in the clinical setting to monitor the development of the disease over time and to guide drug selection. Isolating single CETCs with high recovery and purity from the high background of blood cells is an indispensable prerequisite to investigate cell heterogeneity and provides a tool for a personalized medicine approach. Methods: Blood from patients with non-small cell lung cancer, colon cancer and malignant melanoma was analysed for CETCs using the maintrac approach. Between 8-20 EpCAM positive cells from each patient were isolated individually using a semiautomated capillary approach and deposited one by one into micro cups. For mutational profiling, EGFR, KRAS and BRAF hotspot mutations were analysed in CETCs after whole genome amplification. Results: DNA could be amplified from all individually isolated cells. EGFR mutations were detected in 17% of isolated tumor cells from patients with non-small cell lung cancer; KRAS mutations were detectable in 28% of cells from patients with colon cancer and BRAF mutations in 50% of evaluable cells. A high heterogeneity in mutation status was observed among CETCs within a patient. Conclusions: Individually isolating CETCs from the peripheral blood from patients with non-small cell lung cancer, colon cancer and melanoma allows not only to detect driver mutations but also to determine genotypic heterogeneity between cells and changes over time. Mutations in the CETCs resemble those detected in primary tumors present only in part of the cells. They can be used to monitor the development of disease and its status over time, particularly for its impact in guiding drug selection.
Pyogenic liver abscess: a clinical analysis of 118 cases
Authors: Jian Gong, Wei Dai
Journal: BMJ (2013)

The clinical data of 118 patients with bacterial liver abscess admitted to a tertiary hospital from January 2007 to December 2009 were analyzed retrospectively. Etiology study showed that 45.8% (54/118) cases of bacterial liver abscess were cryptogenic, 40.7% (48/118) were biliary source and 13.5% (16/118) were hematogenous. The positive rate of pus culture was 57.1% (36/63), among which klebsiella pneumoniae accounted for 72.2% (26/36). The positive rate of blood culture was 31.2% (20/64) and klebsiella pneumoniae accounted for 95% (19/20). One hundred and sixteen patients (98.3%) underwent color ultrasound examination with an accuracy rate of 93.2%. 84 patients (71.2%) underwent the CT scan with an accuracy rate of 95.3% and 20 patients underwent MRI with an accuracy rate of 85%. Seventy five patients (63.6%) accepted ultrasound-guided percutaneous aspiration and catheter drainage combined with antibiotic therapy; 40 patients (33.9%) were treated with antibiotics alone. On the discharge 27 patients (22.9%) achieved clinical cure, 87 patients (73.7%) were classified as effective, 4 patients (3.4%) had no effect and no death in this group of patients. The average length of hospital stay was 16 days. Cryptogenic was the most common cause of bacterial liver abscess, biliary source took the second place. Kleibsiella pneumoniae was the predominant organism. Detailed medical history inquiry, physical examination and assistant examination may increase the accuracy rate of diagnosis. Needle biopsy should be performed if necessary. Ultrasound-guided percutaneous aspiration and catheter drainage combined with antibiotics should be the first-line treatment.


Key words: 
Liver abscess; Retrospective studies
儿童铜绿假单胞菌败血症致感染性休克二例
Authors: 邱立, 冯冰
Journal: BMJ (2005)

例1 男,11岁,因发热6 d,头痛伴腹泻1 d入院.查体:体温39.9℃,脉搏160次/min,血压 60/15 mm Hg(1 mm Hg=0.133 kPa),神志清,烦躁不安, 皮肤见淡红色斑丘疹,悬雍垂及上腭见化脓灶,双肺闻散在湿性啰音,心音低钝,腹部拒按,肝肋下2.8 cm,布氏征(+)。
Early intervention for Parkinson disease
Authors: Yuming Xu
Journal: BMJ (2018)

帕金森病是一种起病隐匿、缓慢进展的神经退行性疾病，主要临床特点为进行性加重的运动迟缓、肌强直和静止性震颤。帕金森病早期症状不典型，当出现典型运动症状时，疾病已进展至中晚期。由于该病具有早期进展速度快、晚期进展速度慢的特点，并且目前尚无有效的治疗手段，因此寻找帕金森病的危险因素，进行早期诊断和早期治疗，有助于延缓帕金森病病程，改善预后，提高患者的生命质量。
甲硝唑注射液治疗后出现精神症状一例
Authors: 胡良凯, 张建民, 陈薇敏, 杨伟刚
Journal: BMJ (2009)

患者男,75岁.因慢性胆囊炎急性发作于2009年1月17日入院.入院检查:体温36.5℃,脉搏70次/min,呼吸20次/min,血压160/90 mm Hg(1 mm Hg=0.133 kPa).神志清楚,自主体位,查体合作,对答切题.2年前患脑梗死,无明显后遗症,既往无药物过敏史.入院后查肝、肾功能正常。
Research progress of quantitative perfusion parameters of dynamic contrast-enhanced MRI in diagnosis and efficacy evaluation of uterine tumors
Authors: Jing Zheng, Zhenhua Zhao, Hongjie Hu
Journal: BMJ (2017)

The quantitative parameters based on dynamic contrast-enhanced MRI (DCE-MRI) scan, simulate the distribution of contrast inside and outside of the blood vessels through a variety of tracer kinetic models. The DCE-MRI perfusion parameters now are widely applied in clinical management of uterine tumors, to analyze the microcirculation characteristics in tumor and to guide the diagnosis, tumor grading and efficacy evaluation.


Key words: 
Magnetic resonance imaging; Uterine neoplasms; Diagnoses