tbuckley/cabot-search huggingface dataset:
Similar negative emotional impact on hair loss in neoadjuvant endocrine therapy compared to neoadjuvant chemotherapy in young women with breast cancer from patient reported outcomes.
Authors: Sung-chan Gwark, Sei Hyun Ahn, Woo Chul Noh, Eun Sook Lee, Yongsik Jung, Lee Su Kim, Wonshik Han, Seok Jin Nam, Gyungyub Gong, Seon-Ok Kim, Hee Jeong Kim
Journal: Journal of Clinical Oncology (2020)

e19242 Background: We aimed to evaluate patient-reported outcomes (PROs) in the NEST phase III trial, in which neoadjuvant endocrine therapy (NET) compared to conventional neoadjuvant chemotherapy (NCT) for hormone-responsive lymph node-positive premenopausal breast cancer. Methods: Premenopausal women with estrogen receptor (ER)-positive, HER2-negative, and lymph node-positive premenopausal breast cancer patients were enrolled. Patients were randomized to either 24 weeks of neoadjuvant chemotherapy with doxorubicin plus cyclophosphamide followed by taxane (T) or neoadjuvant endocrine therapy with goserelin and tamoxifen. PROs were assessed at day 1 (baseline) and at the end of treatment, using the breast cancer module of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 23 (EORTC QLQ BR23). ClinicalTrials.gov: NCT01622361. Results: 187 patients were randomly assigned to chemotherapy (n=95) or endocrine therapy (n=92), and 174 patients completed the 24 weeks of neoadjuvant treatment period (n=87, both). Baseline scores were similar between arms. No statistically significant between-treatment differences were observed for the function scales including body image, sexual functioning, and sexual enjoyment although endocrine treatment showed significant improvement in future perspective (HR=8.3, 95% CI:1.72-18.38; P=0.021). Even though no alopecia was reported in NET group, no statistically significant difference between both arms in the “upset by hair loss” was observed, in which NET group showed even worse score. Conclusions: Patients who received NET had significant improvement in a future perspective, however, a similar emotional negative impact on hair loss was observed compared with NCT despite no reported alopecia. Key words: breast cancer, patient-reported outcomes, quality of life, hair loss, EORTC QLQ-BR 23. Clinical trial information: NCT01622361 .
Single-agent ONC201 in recurrent H3 K27M-mutant diffuse midline glioma.
Authors: Isabel Arrillaga-Romany, Sylvia Christine Kurz, Rohinton Tarapore, Ashley Sumrall, Nicholas A. Butowski, Rebecca A. Harrison, John Frederick De Groot, Andrew S. Chi, Nicole A. Shonka, Yoshie Umemura, Yazmin Odia, Minesh P. Mehta, Phioanh Leia Nghiemphu, Timothy Francis Cloughesy, Guangrong Lu, Wolfgang Oster, Joshua E. Allen, Tracy Batchelor, Andrew B. Lassman, Patrick Y. Wen
Journal: Journal of Clinical Oncology (2020)

3615 Background: Recurrent H3 K27M-mutant diffuse midline glioma is a lethal brain tumor that predominantly affects children and young adults and has no effective therapy. ONC201 is a first-in-class orally administered, anti-cancer small molecule that selectively antagonizes the dopamine receptors DRD2/DRD3 and agonizes ClpP, a mitochondrial protease. Prior studies have indicated dysregulated dopamine receptor expression and enhanced ONC201 sensitivity among H3 K27M-mutant gliomas. Methods: Adults with midline H3 K27M-mutant glioma patients were enrolled to a dedicated Phase II clinical trial (NCT03295396), a multi-arm Phase II clinical trial (NCT02525692), and expanded access protocols under the Sponsor’s IND. Results were pooled among patients treated with ONC201 monotherapy through any of these trial with H3 K27M confirmed glioma, progressive and measurable disease by RANO, &gt; 90 days from completion of prior radiation, no evidence of leptomeningeal dissemination, midline location other than primarily pons or spinal cord, and baseline KPS &gt; 60. Using an enrollment cutoff of February 15, 2019 and data cutoff of July 31, 2019, there were 20 patients (NCT03295396, 12; NCT02525692, 7; expanded access, 1). Dosage was 625 mg weekly in 19 and once every 3 weeks in 1. Results: No DLTs or treatment discontinuations due to toxicity occurred. Midline gliomas can exhibit minimal contrast enhancement or exhibit a mixture of contrast-enhancing and non-contrast enhancing regions in the tumor. As a result, blinded independent central review (BICR) of tumor response by MRI was assessed by RANO-HGG and RANO-LGG for each patient to capture contrast-enhancing lesions by T1 post-contrast and non-contrast-enhancing assessments by T2/FLAIR, respectively, in the object response rate. The best response by RANO-HGG or RANO-LGG is 30% (95% CI, 11.9-54.3%). Duration of response by RANO-HGG is median 52.7 weeks (range 15.9-138.3). One patient with stable disease as of this data cutoff has continued on treatment beyond 12 months and recently underwent an investigator-reported PR by RANO-HGG that is pending confirmation. Conclusions: Single agent ONC201 is well tolerated and clinically active in recurrent H3 K27M-mutant diffuse midline glioma patients. Clinical trial information: NCT03295396, NCT02525692 .
Treatment and outcome of patients with uterine carcinosarcoma: Data from developing world.
Authors: Seema Gulia, Anne Srikanth, Dr Ketaki Adsul, Umesh Mahantshetty, Jaya Ghosh, Amita Maheshwari, Sushmita Rath, Shylasree TS, Supriya Chopra, Santosh Menon, Kedar Deodhar, Bharat Rekhi, Palak Popat, Sudeep Gupta
Journal: Journal of Clinical Oncology (2020)

e18102 Background: To evaluate the clinicopathological factors, outcome and prognostics factors of uterine carcinosarcoma. Methods: All patients of uterine carcinosarcoma treated between January 2013 and December 2018 were identified and their clinical, laboratory and imaging details were retrieved from electronic medical record. Details of the treatment received, toxicity profile and outcome were recorded and analyzed. Patients (including stage I) were considered for four cycles of chemotherapy (Paclitaxel +Carboplatin) followed by radiation (EBRT to pelvis with vaginal brachytherapy). Survival analysis was done using the Kaplan–Meier method and compared between treatment groups using the Log-rank test. Results: Of 81 cases, 48 % presented with early stage disease (FIGOI-II) and 52 % with late stage (FIGO III-IV) disease. Median age was 58 years (30-80 years). Most women (83%) were postmenopausal and 80% of them presented with postmenopausal bleeding. Six patients developed carcinosarcoma on adjuvant tamoxifen (given for breast cancer) after a median drug intake of 8 years. In early stage, 10% patients received only surgical treatment; 46% received both chemotherapy (CT) and radiation therapy (RT) while 33 % received RT alone. In advanced stage, 31% received only CT, 14 % received only RT and 33% received both CT and RT after surgery. About 8% of patients had myelosuppression(grade I/II), 10 % had peripheral neuropathy (grade I/II) and 11% had electrolyte imbalance. At a median follow up of 2 years (1- 80 months), median DFS and OS in early stage group was 28.5 months and 31.0 months while in advanced stage group it was 13.0 months and 15.0 months respectively. Distant metastasis (omentum, peritoneum and lung being the common site) were seen in 30% of patients while local relapse was seen in 5 % cases. On univariate analysis stage of disease and receipt of adjuvant therapy were the factors found to be significantly associated with improved OS (p &lt; 0.001) and adjuvant RT alone was associated with improved DFS (p &lt; 0.023). Conclusions: Adjuvant treatment (chemotherapy and or radiation therapy) is associated with improved overall survival in uterine carcinosarcoma, irrespective of stage at presentation.
Association of peripheral blood CD4+ T-cell depletion under temozolomide with inferior survival of patients with IDH wildtype glioblastoma.
Authors: Michael Weller, Ekaterina Terksikh, Manuela Silginer, Carsten Krieg, Patrick Roth, Burkhard Becher, Hans-Georg Wirsching
Journal: Journal of Clinical Oncology (2020)

2548 Background: Standard first line chemoirradiation with temozolomide is associated with distinctive peripheral blood immune cell profiles in IDH wildtype glioblastoma. Whether such profiles at recurrence are associated with survival has not been studied in detail. Methods: Peripheral blood mononuclear cells of 21 healthy donors and of 91 patients with IDH wildtype glioblastoma were analyzed by flow cytometry at 1 st recurrence. Patients received either (i) standard chemoirradiation with temozolomide (TMZ) followed by dose-intensified TMZ at first recurrence within the phase II trial DIRECTOR (N = 52) or (ii) hypofractionated radiotherapy with or without bevacizumab (N = 39) followed by investigators’ choice within the phase II trial ARTE. Patients were classified based on unsupervised analyses of PBMC profiles at 1 st recurrence. Associations with survival were explored in multivariate Cox models controlling for established prognostic and predictive factors. Results: At 1 st recurrence, two patient clusters were identified in the DIRECTOR cohort which differed in CD4+ T-cell fractions, but not with respect to CD8+ T-cells, CD4+;CD25+;FoxP3+ regulatory T-cells, B-cells or monocytes. The composition of CD4+, CD8+ or regulatory T-cell fractions was similar in both clusters. All control samples clustered with the CD4 high cluster. Patients in both clusters did not differ by established prognostic factors, including age, O6-methylguanine-DNA-methyl-transferase ( MGMT) gene promoter methylation, tumor volume, Karfnosky performance score or steroid use. Progression-free survival was similar (CD4 high vs CD4 low 2.1 vs 2.4 months, p = 0.19), whereas post-recurrence overall survival was longer among the CD4 high cluster (12.7 vs 8.7 months, p = 0.004). At 2 nd recurrence after dose-intensified TMZ re-challenge, monocyte fractions increased, whereas memory CD4+ T-cell fractions decreased. Higher memory CD4+ fractions were associated with longer overall survival at 2 nd recurrence (p = 0.004). The reported associations were retained in multivariate Cox models controlling for established prognostic factors. In the ARTE cohort, CD4+ T cell fractions at 1 st recurrence did not differ compared to diagnosis (p = 0.91) and there were no associations with bevacizumab (p = 0.28) or survival (p = 0.74), supporting that the effects observed in the DIRECTOR cohort were driven by TMZ. Conclusions: We conclude that TMZ-associated memory CD4+ T-cell depletion may have deteriorating effects on the survival of glioblastoma patients.
社区卫生服务门诊日志中的信息及利用
Authors: 张晓林, 尚晓梅, 李炜
Journal: BMJ (2008)

患者来社区卫生服务站就诊,我们最先做的一件工作就是对每一位来就诊的患者进行基本情况的登记,这个登记本也就是我们所说的门诊日志.可是,除了笼统地知道每天我们接待了多少患者、每月月底统计工作量使用一下门诊日志外,很少分析和关注这个登记本。
Assessment of 5-methylcytosine and 5-hydroxymethylcytosine technologies in contrived ctDNA-like samples.
Authors: Eun-Ang Raiber-Moreau, James Hadfield, Darren Hodgson, Marilou Wijdicks
Journal: Journal of Clinical Oncology (2020)

e15585 Background: Epigenomic changes to DNA are early driving events in tumorigenesis and are specific markers of the tumour and its microenvironment. Cell-free DNA that is released from the tumour microenvironment can potentially be used for the detection of tumour-specific epigenomic changes for cancer liquid biopsy testing. In this study, we assessed the robustness of 5-methylcytosine and 5-hydroxymethylcytosine technologies in contrived ctDNA-like samples from NSCLC. Additionally, we assessed the limit of detection of the tumour fraction within the tested dilution range looking at a subset of differential epigenomic marks. Methods: 4 NSCLC tumour and buffy coat DNA samples were commercially obtained and processed to generate contrived tumour DNA dilution mimicking circulating tumour DNA at varying tumour fractions. Samples were sent in triplicate to multiple epigenomic assay providers for analysis. The robustness i.e. reproducibility and limit-of-detection within the tested range was determined. Results: Technical replicates all passed method-specific quality controls and were highly reproducible. Cancer specific differentially-methylated or hydroxymethylated regions were determined for each individual tumour sample as a “sample-specific cancer signature”; when applied to the tumour dilution samples, these signatures were capable of distinguishing all tumour dilutions down to 0.05% from normal background DNA. Detection of differential methylation and hydroxymethylation regions was reproducible across technical replicates for all four NCSLC samples at &gt; 0.05%. Generation of pooled methylation “signatures” derived from commercially available healthy plasma and cancer tissue datasets could still detect cancer DNA in these four NCSLC samples at &gt; 0.1% tumour fraction. Conclusions: Our pilot study showed that all assessed technologies generated reproducible, robust data and could detect ctDNA at even clinically relevant levels for early stage cancer. One limitation of this study was the small number of “n” and the use of sonicated contrived sample that may induce artificial bias and reduce sensitivity highlighting a requirement for the development of reference material in the community. The ability to detect cancer-specific epigenomic changes from liquid biopsy with high sensitivity offers new promising avenues for early detection of cancer, which can increase the chances of successful treatment.
Perinatal management and outcomes of triplet and multiple pregnancy
Authors: Chun Yang, Dao-fang Wang, Ming-feng Zhuang
Journal: BMJ (2008)

Objective To analyze clinical management and outcomes of perinatal fetuses born in triplet and multiple pregnancy.Methods Data of clinical management and outcomes of 55 perinatal fetuses born during 1996 to 2005 by women with triplet and multiple pregnancy were analyzed retrospectively.Results Antenatal check-up was performed regularly for 1/6 of those pregnant women during 1996 to 2000,as compared to that of 8/11 during 2001 to 2005(P<0.05).No significant difference in incidence of varied obstetric complications was found between those during 1996 to 2000 and during 2001 to 2005.Average gestational week at birth was(32.7±2.8)and(35.1±1.9)weeks(P<0.05),and averagebirth weight was(1561±471)grams and(1987±453)grams(P<0.01),respectively for them during 1996 to 2000 and during 2001 to 2005.Caesarean section was performed more for the pregnant women in the earlier first five years than in the later five years,but not reaching statistical significance.Incidence of neonatal complications significantly decreased in the later five years than that in the earlier five yeats,including hyaline membrane disease,neonatal asphyxia,infectious diseases,intracranial hemorrhage and pulmonary hemorrhage(P<0.05),but difference in incidence of apnea and low body temperature between the earlier and later five years did not reach statistical significance.Perinantal mortality was 8 in 35 births in the later five years,as compared to that of 12 in 20 births in earlier five years(P<0.01).Conclusions Outcomes of perinatal fetuses in triplet and multiple pregnancy can be improved by combined action of obstetricians and pediatricians,including regular antenatal examination,active prevention and treatment for pregnant complications and preterm infant diseases,earlier admission waiting for delivery to prolong gestational weeks and increase birth weight,and applying antenatal dexamethasone therapy.

Key words: 
Pregnancy,multiple; Premature birth; Infant mortality
Feasibility of real-time serial comprehensive tumor analytics: Pilot study of olaparib and durvalumab in metastatic triple negative breast cancer (mTNBC).
Authors: Allen Li, Marilyne Labrie, Jacqueline Vuky, Jeong Youn Lim, Brett Johnson, Sam Sivagnanam, Courtney Betts, Lisa Coussens, Christopher L. Corless, Raymond C. Bergan, Joe W. Gray, Gordon B. Mills, Zahi Ibrahim Mitri
Journal: Journal of Clinical Oncology (2020)

e13092 Background: Longitudinal analysis of serial tumor biopsies is an under-utilized approach to studying adaptive mechanisms of resistance. We have established a comprehensive analytic platform to evaluate real-time trial sample analysis to inform precision oncology combinations in mTNBC. The primary endpoint of the study is feasibility of completing all CLIA assays within 28 days of biopsy. Methods: Following a pre-treatment biopsy and 4 weeks of olaparib monotherapy mTNBC patients underwent an on-treatment (tx) biopsy and durvalumab was added to their therapy. Pre- and on-tx biopsies underwent comparative analysis using CLIA assays (immunohistochemistry-IHC, whole exome seq, RNAseq and phospho-proteomics) as well as research assays (multiplex IHC-mIHC, cyclic immunofluorescence-IF, and reverse phase protein array-RPPA). Results: Serial biopsies were obtained from all 3 enrolled patients, and the primary endpoint was achieved for all patients (Table). Treatment was well tolerated, and 2 patients achieved clinical benefit &gt; 6 months. In one patient with a prolonged CR ( &gt; 18 months), the on-tx sample exhibited dramatic changes in protein network rewiring by protein data analysis (RPPA, cyclic-IF), and an increase in immune infiltrate by mIHC. Conclusions: This pilot confirmed the feasibility of rapid real-time analysis to inform treatment decisions. This led to the development and initiation of biomarker driven olaparib combination trials in mTNBC at our institution. Clinical trial information: NCT03544125 . [Table: see text]
Retrospective analysis of clinical profiles of Brucellosis
Authors: Li-hua Dai, Jun Li
Journal: BMJ (2013)

To analyze the clinical characteristics, complications and management of Brucellosis. As a retrospective review, 23 patients with Brucellosis admitted into Peking University First Hospital over a 10-year period were reviewed. Most of them were middle-aged males. Common presenting clinical manifestations included high fever, sweating, arthralgia and headache. Splenomegaly was more common than hepatomegaly. There were liver injury (n=15), transient proteinuria (n=6), secondary hemophagocytic syndrome (n=2) and renal failure with infective endocarditis, pneumonia with infective endocarditis, renal abscess (n=1). Most of them were treated effectively with combination therapy. The clinical features of Brucellosis are both complicated and atypical.


Key words: 
Brucellosis
急性肠系膜静脉血栓形成19例分析
Authors: 余开焕, 童仕伦, 邓细佑
Journal: BMJ (2005)

对自1985年1月至2004年8月武汉大学人民医院收治的19例急性肠系膜静脉血栓形成患者的临床资料进行回顾性分析.结果治愈16例,死亡3例.手术前确诊4例,2例保守治疗成功.17例手术治疗,平均切除肠管240 cm.结果表明,厌食、腹部饱胀不适、症状体征不符的腹痛和可能存在的高凝状态是早期诊断本病的线索,彩色多普勒超声及CT扫描血管重建检查对早期诊断有重要意义.早期诊断及适当的溶栓抗凝治疗可避免肠切除。
Highlights of BRCA genetic testing in prostate cancer from a real-world patient cohort in Australia.
Authors: Inga Tinton, Lara Spence, David H. Henry
Journal: Journal of Clinical Oncology (2020)

e13574 Background: There is an increase in interest and awareness in BRCA 1/2 testing recently. However, despite high awareness of these tests due to their frequent use among patients with certain cancer types such as ovarian cancer or breast cancer, BRCA testing is still only emerging in the prostate cancer (PC) treatment landscape. This study aims to understand what is driving the interest and use of BRCA testing in PC as well as the main barriers to testing in Australia. Methods: Between September 2019 and November 2019, n = 51 physicians of different specialties (n = 26 medical oncologists, n = 11 urologists, n = 14 pathologists) in Australia provided their quantitative and qualitative insights on BRCA testing. Medical oncologists and urologists (n = 37) also submitted patient tissue record forms of PC patients (n = 102) who received at least one biomarker test. The findings are derived from perceptual questionnaires, patient tissue record forms, and qualitative interviews. Results: The data suggests high (100%) awareness of BRCA testing in PC among medical oncologists and urologists, however that’s not the case among pathologists (36%). BRCA testing was seen in almost half of the patient records collected, primarily as blood tests (40%) as opposed to tissue (28%) or any other tests. Larger number (40%) of blood tests are carried out post-diagnosis with almost half (46%) of them initiated due to family history. Prior treatment history and patient request are more common patient selection criteria when deciding whether to test any PC patient for BRCA. The main barrier (64%) to BRCA testing is lack of funding/reimbursement for the test in PC at the moment. Only clinical trial PC patients typically have access to funded BRCA tests or those patients who are supported by the genetic counsellor program. Conclusions: Driven by significant uptake in ovarian and breast cancer and high awareness among oncologists and urologists, BRCA testing for prostate cancer is being increasingly used in the clinical setting in Australia. However, significant barriers remain; addressing these barriers should result in further uptake.
Del-1 and MFG-E8 expression to differentially modulate prognosis of patients with triple-negative breast cancer.
Authors: Soo Jung Lee, Ho Yong Park, Jin Hyang Jung, Jeeyeon Lee, In Hee Lee, Ji-young Park, Yee Soo Chae
Journal: Journal of Clinical Oncology (2020)

e13093 Background: Del-1 was previously found to be prognostic biomarker in early breast cancer patients. Del-1 shares both structural and functional homology with Milk fat globule-epidermal growth factor-factor VIII (MFG-E8). To date, the biological functions of Del-1 and MFG-E8 have not been sufficiently compared in side-by-side experiments. MFG-E8 is a secreted glycoprotein from macrophages that promotes clearance of apoptotic cells. In this study, we investigated the function of MFG-E8 and Del-1 and prognosis in a large cohort of EBC patients. Methods: The MFG-E8 levels were measured using a qRT-PCR in breast cancer cells (MDA-MB-231, Hs578T, MCF7, SK-BR3, and T-47D), and tissues from 20 patients with EBC. The effects of MFG-E8 and Del-1 on cell proliferation, migration, and invasion were determined using MTT, wound healing, and Matrigel Transwell assays. The expressions of MFG-E8 and Del-1 protein were detected by immunohistochemical staining in 436 tumor tissues. The relationship between MFG-E8, Del-1 expression levels and clinicopathological features were evaluated. Results: MFG-E8 and Del-1 levels were significantly elevated in MDA-MB-231 and Hs578T cell lines (p &lt; 0.001). Given that MFG-E8 and Del-1 share similar protein structure, we wanted to explore the effect of dual knockdown of MFG-E8 and Del-1 in migration and invasion assay. As expected, knockdown of Del-1 alone decreased cell migration in TNBC cell lines, but dual knockdown of MFG-E8 and Del-1 showed reduction was restored. Dual knockdown of MFG-E8 and Del-1 showed consistent result in invasion assay. Down-regulation of Del-1 inhibited TNBC cells invasion and recovered by the MFG-E8 knockdown. Interestingly, for the 436 patients, Del-1 high- and MFG-E8 low- expression shows correlation with aggressive histologic grade, high Ki-67 (p &lt; 0.001 and p = 0.042, respectively) and shorter survival outcome (distant disease free survival p = 0.028, breast cancer specific survival p = 0.001). Conclusions: Overall, these findings suggest that MFG-E8 and Del-1 protein expression could be a prognostic marker for patients in triple negative breast cancer (TNBC). Thus, MFG-E8 reduction may contributes to tumorigenesis by increasing Del-1. However, functions of Del-1 and MFG-E8 have not yet been thoroughly analyzed, further studies are required.
沙袋压迫法治疗帽状腱膜下大量出血一例
Authors: 孙光茂, 徐爱红, 李强
Journal: BMJ (2005)

患儿女,8岁,因头晕头胀10 d入院.患儿10 d前头部轻微碰伤后感头晕、头胀,呕吐数次,为胃内容物.体格检查:体温37.2℃,脉搏100次/min,呼吸24次/min,血压98/70 mm Hg(1 mm Hg=0.133 kPa),神志清醒,精神不振,全身皮肤黏膜未见出血点.头围62 cm,前额及全部发际内均有囊样波动感,有轻度触痛。