tbuckley/cabot-search huggingface dataset:
Distinct transcriptional profiles in plasma exosomes associated with recurrence of nasopharyngeal carcinoma patients with standard treatment.
Authors: Yongjiang Li, Xue Zheng, Xiaoqi Xie, Yukai Hu, Jingbo Kang, Jiyu Wei, Ruoyu Wang, Beibei Mao, Baolin Qu, Ying Yang, Xianfeng Li, Xueying Fu, Qingyun Li, Henghui Zhang, Junjie Wang, Feng Wang
Journal: Journal of Clinical Oncology (2020)

6534 Background: Nasopharyngeal carcinoma (NPC) is endemic with a high prevalence in Southern China, Asia,cetuximab and North Africa. Exosomes are small vesicles containing a wide range of functional proteins, mRNA and miRNA. In the progression of NPC, the tumor cells constantly release exosomes into the surrounding environment and also into the circulating blood. The aim of this study was to explore the association between RNA expression in plasma exosomes and prognosis of NPC patients after standard treatment. Methods: In this retrospective study, a total of 25 eligible NPC patients were included: 12 patients in the recurrence (R) subgroup and 13 patients in the no recurrence (NR) subgroup. RNA was extracted from the exosomes of plasma specimens which were collected at West China Hospital, Sichuan University. Gene expression profiles were conducted by using the RNA-sequencing platform. The DESeq2 package was used to analyze the differentially expressed genes (DEGs) between R and NR subgroups. The gene set variance analysis (GSVA) was performed to explore C5 gene sets enrichment related to the recurrence after standard treatment. Results: We observed 332 DEGs between R and NR subgroups, which include 125 up-regulated and 207 down-regulated genes (R vs. NR,∣log2fold change∣&gt;1, p&lt;0.05). Moreover, hierarchical clustering analysis of the 332 DEGs revealed that all samples clustered into two subgroups, with cluster 1 containing 82% (9/11) recurrence patients and cluster 2 containing 79% (11/14) no recurrence patients. Further, univariate Cox regression analysis showed that 293 out of 332 DEGs were significantly correlated with DFS ( p&lt;0.05), such as TRAM1, CAPN1, SAT1 and ACTB. GSVA and Log Rank test of survival data demonstrated that a total of 824 pathways/biological processes were significantly different between R andNR subgroups ( p&lt;0.05). Specifically, the top 9 pathways/biological processes, such lipoxygenase pathway, rough endoplasmic reticulum membrane and low density lipoprotein particle clearance, was mainly enriched in the NR subgroup ( p &lt;0.001). Conclusions: Profiling of plasma exosomes RNA in NPC patients reveals distinctive gene expression pattern between patients with or without recurrence. Further functional analysis revealed that top enriched 9 pathways/biological processes may correlate with a favorable prognosis and are worth investigating. Moreover, for the prognosis of patients with NPC, RNA expression of plasma exosomes may be a potentially valuable research object.
What do differences in case fatality ratios between children and adults tell us about COVID-19?
Authors: Fabio Midulla, Luca Cristiani, Enrica Mancino
Journal: European Respiratory Journal (2020)

We thank S. Ebmeier and A.J. Cunnington for their commentary on our editorial [1], providing another point of view on such a controversial topic. In their letter, S. Ebmeier and A.J. Cunnington assume that the greater burden of coronavirus disease 19 (COVID-19) in adults may be related to the absence in the population of prior immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as occurred in fully susceptible populations during previous viral epidemics. In particular, Shanks et al . [2] report that the measles mortality rate in a fully susceptible population during the 1846 measles epidemic was higher in adults and in children aged <2 years. However, nowadays, children younger than 5 years and adults older than 20 years are still more likely to suffer from measles complications, despite not being fully susceptible [3]. Moreover, Strebel et al . [4] reported that the case fatality ratio is still high in children aged <1 year, lower in children aged 1–9 years, and then rises again in teenagers and adults. The reported data suggest that greater morbidity and mortality in adults is not a unique feature of first-contact measles epidemics. Other reasons, rather than absence of prior immunity, could play a crucial role in the coronavirus dilemma that surrounds children <https://bit.ly/36BzTaD>
深圳市实施家庭医生责任制项目路径的分析与思考
Authors: 赖光强, 陈皞璘, 张校辉
Journal: BMJ (2009)

家庭医生责任制是以社区为载体、家庭为单位、个人为目标,以契约服务的形式为家庭及其每个成员提供连续、协调、可及性的综合医疗保健服务模式,是改变医生坐诊模式,和谐医患关系,提高社区居民健康素养和健康水平,实现人人享有卫生保健目标的重要途径.但家庭医生责任制绝非社区卫生服务的翻版以及简单的合同式约束,它应该具备充分的接受方适应、提供方准备以及卫生服务的战略调整.深圳市实施家庭医生责任制项目的路径可供借鉴。
Advances in diagnoses and treatment for liver cirrhoses complicated with spontaneous bacterial peritonitis
Authors: 陈倩, 邹健, 张渊
Journal: BMJ (2004)

自发性细菌性腹膜炎(spontaneous bacterial peritonitis, SBP)指无腹腔脏器穿孔而发生的腹腔急性细菌感染,最常发生于肝硬化失代偿期患者,也见于其他严重肝脏疾患,如重症肝炎、肝癌、暴发性肝功能衰竭等.肾病综合征、心源性腹水、孕产妇、术后乳糜性腹水亦可发生SBP,但发生率相对较低.SBP多发生于腹水的基础上,亦有报道可发生于无腹水的肝硬化患者,据国内统计SBP占住院肝硬化腹水患者的20.6%,肝硬化无腹水患者的10.3%,其发生率与基础肝病的严重程度有关,如合并肝性脑病者SBP可达36%[1]。
Efficacy of Prolene 3D patching in tension-free hernioplasty for femoral hernia via femoral approach
Authors: Jianpeng Huang
Journal: BMJ (2014)

A total of 114 cases of femoral hernia undergoing 3D Prolene patching via femoral approach were examined for duration of surgery, length of stay, recurrence, postoperative pain and complications.Among them, 53 cases received both pre- and post-operative Doppler ultrasonic examinations.The vein thrombus, diameter and flow rate of femoral vein were observed to compare with the pre-operative data to learn whether it had difference or not.The operative duration was 13.3 minutes.There was no event of recurrence, compression, stricture or thrombosis of femoral vein.


Key words: 
Hernia, ventral; Reconstructive surgical procedures
Diagnostic utility of bronchoscopy in newly diagnosed acute leukemia patients.
Authors: Thomas Curley, Kristin Lynn Koenig, Shylaja Mani, Mark Lustberg, Gregory Behbehani, Bhavana Bhatnagar, James Stewart Blachly, Tamanna Zohra Haque, Karilyn T.M. Larkin, Meixiao Long, Alice S. Mims, Sumithira Vasu, Sarah Allison Wall, John C. Byrd, Alison R. Walker, Nicole Renee Grieselhuber
Journal: Journal of Clinical Oncology (2020)

e19510 Background: Over 40% of newly diagnosed acute leukemia patients receiving induction therapy develop acute respiratory failure. Bronchoscopy is a valuable tool for evaluating airway disease, but its diagnostic yield in this setting has not been fully explored. Methods: We performed a retrospective chart review of 75 newly diagnosed acute leukemia patients who had bronchoscopies. Data recorded prior to bronchoscopy included age, diagnosis, induction treatment regimen, chest imaging, assisted ventilation, duration of neutropenia and antibiotic therapy and microbiological studies. Bronchoalveolar lavage (BAL) cultures were sorted by organism, as well as by other pathologic findings. The primary outcome was antibiotic change supported by culture data. Results: The study population is summarized in the table. Induction regimen backbones included 7+3 (51), 7+4+ATRA (2), decitabine (12), hyperCVAD (2), AYA (3), other (1) and none (4); 18 patients were treated on clinical trial. Average days of neutropenia was 10.92 and average days of antibiotic therapy was 10.57. Thirty-eight patients had chest infiltrates, 11 received NIPPV, and 17 were mechanically ventilated. We identified 24 patients with +BAL studies. Of these, 37.5% (9) had + blood, urine or sputum studies before bronchoscopy, but only 3 had cultures positive for the same organism as the BAL. Of 51 patients with –BAL studies, 33.3% (17) had prior negative cultures. Infections were most commonly bacterial (15, 62.5%), followed by viral (5, 20.8%) and fungal (4, 16.7%). The most common organisms were rhinovirus, vancomycin sensitive Enterococcus (4, 16.7% each) followed by VRE, Candida albicans and MRSA (2, 8.3% each). Five patients (6.7%) had alveolar hemorrhage. Of the 24 patients with +BAL cultures, bronchoscopy findings supported changing antibiotics in 18. In contrast, antibiotics were changed in 16 patients without +BAL cultures. Conclusions: We investigated the utility of bronchoscopy on AL patients during their initial admission. BAL cultures were positive in 32% of newly diagnosed AL patients undergoing bronchoscopy. However, +BAL cultures identified a new organism in 87.5% and guided antibiotic therapy in 75% of these patients. Further studies will be needed to establish predictors of bronchoscopy findings in this patient population. [Table: see text]
A phase I/II study of rovalpituzumab tesirine in delta-like 3-expressing, advanced solid tumors.
Authors: Aaron Scott Mansfield, David S. Hong, Christine L. Hann, Anna F. Farago, Himisha Beltran, Saiama Naheed Waqar, Andrew Eugene Hendifar, Lowell Brian Anthony, Matthew H. Taylor, Alan Haruo Bryce, Scott T. Tagawa, Karl D. Lewis, Jiaxin Niu, Christine H. Chung, James M. Cleary, Michael Rossi, Carrianne Ludwig, Ricardo Valenzuela, Yan Luo, Rahul Raj Aggarwal
Journal: Journal of Clinical Oncology (2020)

3552 Background: Delta-like 3 (DLL3) is highly and specifically expressed in solid tumors, such as neuroendocrine carcinomas (NECs), malignant melanoma (MM), and medullary thyroid carcinoma (MTC). Rovalpituzumab tesirine (Rova-T) is a DLL3-targeting antibody-drug conjugate. Methods: This Phase 1/2 study (NCT02709889) enrolled patients with relapsed/refractory DLL3+ (&gt;1% by IHC) advanced solid tumors and ECOG performance status of 0-1. Rova-T was given IV at 0.2, 0.3, or 0.4 mg/kg on d 1 of each 6-wk cycle (q6wk) for dose escalation (3+3 design) in disease-specific cohorts in Phase I. The recommended Phase 2 dose (RP2D) was tested in Phase II. Safety and dose-limiting toxicities (DLTs) were primary endpoints; efficacy outcomes were secondary endpoints. Results: The study enrolled 200 patients; 101 had NECs (large cell NEC [n=13], neuroendocrine prostate cancer [n=21], high-grade gastroenteropancreatic NEC [n=36], other [n=31]) and 99 had other solid tumors (MM [n=20], MTC [n=13], glioblastoma [GBM; n=23], other [n=43]). The median age was 61 y (range, 28-84); 63% were male. The RP2D was 0.3 mg/kg q6wk for 2 cycles in all cohorts. There were 7 DLTs in 5 patients: 2 with 0.2 mg/kg (Grade [Gr] 3 photosensitivity reaction, Gr 3 dyspnea), 2 with 0.3 mg/kg (1 with Gr 2 effusion, Gr 3 tumor lysis syndrome, and Gr 3 rhabdomyolysis; 1 with Gr 4 kidney injury), and 1 with 0.4 mg/kg (Gr 4 thrombocytopenia). Despite only 1 DLT identified with 0.4 mg/kg, the totality of the safety data suggested that this dose is not well tolerated. Common adverse events (AEs) in patients given 0.3 mg/kg (n=145) are shown (Table). Serious AEs occurred in 77/145 patients (53%), most commonly (≥3%) malignant neoplasm progression (n=18; 12%), pleural effusion (n=7; 5%), pericardial effusion (n=6; 4%), and dyspnea (n=5; 3%). The objective response rate (ORR) was 11% (21/200): 14 had NEC, 2 had MM, 2 had MTC, 2 had small cell carcinoma (SCC) not of lung origin (all partial responses), and 1 had GBM (complete response). In patients with NECs given 0.3 mg/kg, ORR, clinical benefit rate, and progression-free survival trended in favor of those with high DLL3-expressing tumors (≥50% by IHC) which represented 51% of NECs. Conclusions: Rova-T was tolerable in patients with advanced solid tumors at 0.3 mg/kg q6wk for 2 cycles. Antitumor activity was observed in patients with NEC, MM, MTC, SCC, and GBM. Clinical trial information: NCT02709889 . [Table: see text]
Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma: A randomized, phase II, multicenter, open-label study (DESTINY-Gastric01).
Authors: Kohei Shitara, Yung-Jue Bang, Satoru Iwasa, Naotoshi Sugimoto, Min-hee Ryu, Daisuke Sakai, Hyun Cheol Chung, Hisato Kawakami, Hiroshi Yabusaki, Jeeyun Lee, Kaku Saito, Yoshinori Kawaguchi, Takahiro Kamio, Akihito Kojima, Masahiro Sugihara, Kensei Yamaguchi
Journal: Journal of Clinical Oncology (2020)

4513 Background: T-DXd is an antibody-drug conjugate composed of an anti-HER2 antibody, cleavable tetrapeptide-based linker, and topoisomerase I inhibitor. In a phase 1 trial of T-DXd (5.4 or 6.4 mg/kg), the objective response rate (ORR) was 43.2% (19/44) and median progression-free survival (mPFS) was 5.6 mo in patients with advanced HER2+ gastric cancer (GC). DESTINY-Gastric01 (DS8201-A-J202; NCT03329690) is an open-label, multicenter, randomized, phase 2 study of T-DXd in HER2-expressing advanced GC or GEJ adenocarcinoma; results are from the primary analyses for ORR and interim overall survival (OS) in HER2+ patients. Methods: Patients with centrally confirmed HER2+ (IHC 3+ or IHC 2+/ISH+ on archival tissue) GC that progressed on ≥ 2 prior lines were randomized 2:1 (T-DXd 6.4 mg/kg q3w or physician’s choice [PC] irinotecan or paclitaxel). All patients received prior HER2 therapy. Stratification factors were region, ECOG PS (0;1), and HER2 status. The primary endpoint was unconfirmed ORR by independent central review. Secondary endpoints were OS (alpha controlled), PFS, disease control rate (DCR), duration of response (DOR), and safety. Results: 187 patients received T-DXd (n = 125) or PC (n = 62 [55 irinotecan; 7 paclitaxel]); 79.7% Japan, 20.3% Korea. Patients had a median of 2 prior lines of therapy, and 44.4% had ≥ 3. At data cutoff (8 Nov 2019), 22.4% of T-DXd and 4.8% of PC patients remained on treatment. ORR was 51.3% (61/119; 11 CR and 50 PR) with T-DXd vs 14.3% (8/56; all PR) with PC ( P &lt; .0001); confirmed ORR, 42.9% vs 12.5% ( P &lt; .0001); DCR, 85.7% vs 62.5% ( P = .0005); mDOR, 11.3 vs 3.9 mo; mPFS, 5.6 vs 3.5 mo (HR, 0.47 [95% CI, 0.31-0.71]; P = .0003). OS was significantly prolonged with T-DXd (mOS, 12.5 vs 8.4 mo; HR, 0.59 [95% CI, 0.39-0.88]; P = .0097; prespecified O'Brien Fleming boundary, P = .0202); 12-month OS, 52.1% vs 28.9%. Grade ≥ 3 AEs occurred in 85.6% of patients with T-DXd vs 56.5% with PC; the most common were neutrophil count decreased (51.2%; 24.2%), anemia (37.6%; 22.6%), and white blood cell count decreased (20.8%; 11.3%). 12 patients (9.6%) had T-DXd–related interstitial lung disease (ILD; 2 grade 3, 1 grade 4, no grade 5) vs 0 with PC. 1 drug-related death (pneumonia [non-ILD] in the T-DXd arm) occurred. Conclusions: T-DXd demonstrated statistically significant and clinically meaningful improvements in ORR and OS compared with standard chemotherapy (paclitaxel or irinotecan) in patients with HER2+ advanced gastric or GEJ adenocarcinoma. Clinical trial information: NCT03329690 .
Influence of urokinase gene knockout on tissue levels of biogenic amines in mice with melanoma.
Authors: Irina V. Kaplieva, Elena M. Frantsiyants, Ekaterina I. Surikova, Irina V. Neskubina, Valeria A. Bandovkina, Lidia K. Trepitaki, Ludmila A. Nemashkalova, Viktoria V. Pozdnyakova, Yuriy V. Przhedetskiy, Natalia A. Zakharova, Olga V. Khokhlova, Viktoria Yu. Przhedetskaya, Oleg I. Kit
Journal: Journal of Clinical Oncology (2020)

e22109 Background: The plasminogen activation system and biogenic amines are involved in melanoma pathogenesis, but currently, the mutual influence of the components of these systems on each other is unknown. The purpose of the study was to reveal the dynamics of biogenic amines in the brain and intact and tumorous skin (B16/F10 melanoma) in C57BL/6-PlautmI.IBug-ThisPlau6FDhu/GFDhu mice with uPA gene knockout. Methods: The study included male and female C57BL/6-PlautmI.IBug-This Plau6FDhu/GFDhu mice, n = 38; the comparison group included C57BL/6 mice without uPA gene knockout, n = 61. Melanoma was transplanted under the skin of the back. Levels of biogenic amines were measured in tissues taken in week 3 of carcinogenesis by ELISA using standard test systems (Cusabio, China). Results: The total content of biogenic amines was elevated in tissues of intact C57BL/6-PlautmI.IBug-ThisPlau6FDhu/GFDhu mice: in the skin – due to the noradrenaline (NA) rise by 4.8 times in males and by 4.9 times in females, histamine (H) – by 3.6 times in males and 1.6 times (p &lt; 0.05) in females, serotonin (5HT) by 3.4 times in males and 8.3 times in females; in the brain – due to the NA rise by 3.5 times in males and 3.2 times in females, dophamine by 2.1 times in males and 2.9 times in females, while H levels declined. Distinctive features of the melanoma development in C57BL/6-PlautmI.IBug-ThisPlau6FDhu/GFDhu mice included: lower levels of adrenaline with high NA concentrations and an enhanced synthesis and inactivation of 5HTin the brain. The content of catecholamines in the tumor nodes was the same as in C57BL/6 mice, with a high concentration of H recorded in the tumor and skin, together with a high 5HT level in the skin. Conclusions: The uPA gene knockout limits the development of stress at the central regulatory and peripheral effector levels, and modulates the immune antitumor response by increasing serotonergic mediation in the brain and increasing serotonin and histamine levels in the skin of mice with B16/F10 melanoma.
Genomic biomarkers to determine survival in Multicenter Study of RAS mutations (MURAS) in patients with colorectal liver metastases receiving Y90 radioembolization treatment.
Authors: Meaghan Dendy Case, Anish Ghodadra, Paula M. Novelli, Vincent Wu, Suvranu Ganguli, Moritz Wildgruber, Michael Kohler, Charles Robinson, Charles Kim, David S. Wang, Daniel Y. Sze, Kenneth Kolbeck, Lori Russell, Johannes M. Ludwig, Johannes Uhlig, Kevin Kim
Journal: Journal of Clinical Oncology (2020)

e16119 Background: Assessment of the clinical outcomes and prognostic value of genomic mutations in colorectal liver metastases treated with Y90 radioembolization. Methods: Multi-institution retrospective study of patients who underwent Y-90 radioembolization treatment after tumor genotyping was completed for CRLM. Patients treated between 2008 and 2019 were included from 7 institutions within the United States and Europe. Patient demographics, tumor characteristics, pre- and post- treatment regimens, serum laboratory evaluation and overall survival were analyzed between patients with differing histopathologic and genomic status. Tumor genotyping was obtained for KRAS, BRAF, PIK3CA, AKT, MEK, NRAS and MMR genes. Kaplan-Meier survival estimation and multivariate Cox regression were analyzed. Results: 434 patients treated with Y90 radioembolization fulfilled the inclusion criteria. Of the total cohort, 399 patients were available who had sufficient documented tumor profiling data. Average age at diagnosis was found to be 58.8 years for all patients (60.1% male, 39.9% female). Decreased survival post Y-90 treatment was shown in those patients with increased number of documented tumor mutations (n = 0,1 or ≥2 mutations: median OS 9.63 mos vs. 6.2 mos vs. 5.3 mos; p &lt; 0.0001). Additionally, the median survival in patients with mutated BRAF was 5.0 months, as compared to 9.4 months in those patients with wild-type BRAF (p = 0.0009). Primary colon cancer sidedness was also shown to demonstrate significant difference in survival post-Y90 treatment with left sided primaries showing improved median overall survival (left = 7.5 mos vs. right = 6.3 mos; p = 0.04.) Patient demographics including gender, age and race were not shown to be significant in overall survival post-Y90 treatment (p-values &gt; 0.05). Number of tumor mutations (p &lt; 0.0001, HR = 1.69 CI: 1.39-2.05), BRAF status (p = 0.02, HR = 2.6 CI:1.20-4.9), primary sidedness (p = 0.01, HR = 0.65 CI:0.47-0.90), pre-treatment neutrophil-lymphocyte ratio (p = 0.04, HR = 1.42 CI: 1.02-1.98) and KRAS mutation status (p &lt; 0.0001, HR = 1.81 CI: 1.45-2.26) all persisted as significant predictors of survival on multivariate analysis. Conclusions: Number of tumor mutations, BRAF mutation status, primary tumor sidedness, neutrophil-lymphocyte ratio and KRAS mutation status are all shown to be significant prognostic factors in patients with colorectal liver metastases receiving Y90 radioembolization.
Identification of two DNA methylation subtypes of Waldenström's macroglobulinemia with plasma and memory B cell features
Authors: Damien Roos-Weil, Brian Giacopelli, Marine Armand, Véronique Della Valle, Hussein Ghamlouch, Camille Decaudin, Marlen Metzner, Junyan Lu, Magali Le Garff-Tavernier, Veronique Leblond, Paresh Vyas, Thorsten Zenz, Florence Nguyen-Khac, Olivier A Bernard, Christopher C. Oakes
Journal: Blood (2020)
Transcatheter arterial embolism for postpartum hemorrhage
Authors: Yan Sun, Yang Liu, Xiang-qian Kong, Xing Jin, Xue-jun Wu, Hai Yuan
Journal: BMJ (2012)

We reviewed the clinical data of 24 patients with postpartum hemorrhage undergoing transcatheter arterial embolism from March 2009 to September 2011.Twenty out of 24 patients underwent uterine artery embolism,while other 4 underwent internal iliac artery embolism.The hemorrhage reduced markedly 2 to 9 min after arterial embolism in all patients,except 2 who underwent secondary embolism due to the intermittent postoperative hemorrhage. The postoperative complications included low fever and discomfort in lower abdomen.Nineteen patients were followed up for a mean period of ( 17.3 ± 1.1 ) months,no recurrent hemorrhage was observed after discharge.The normal menstrual cycle recovered 4 to 6 months after operation.Three patients underwent pregnancy successfully after discharge.The results indicate that transcatheter arterial embolism is safe and effective in the treatment of postpartum hemorrhage and it should be recommended as a feasible choice in clinical practice.

Key words: 
Embolization,therapeutic;  Postpartum hemorrhage
1994年与2003年育龄妇女人工流产分布及其相关因素分析
Authors: 吴虹桥, 董丽萍
Journal: BMJ (2006)

回顾性分析在常州市肿瘤医院做人工流产的育龄妇女的病历资料,1994年506人,2003年630人.分析内容包括一般情况、婚育状况、终止妊娠原因等.1994年人工流产的最大年龄47岁,最小年龄19岁,其中90%集中在20.7～40.6岁;2003年人工流产的最大年龄47岁,最小年龄17岁, 其中90%集中在20.4～39.6岁.1994年人工流产者中未婚192人,占37.9%;2003年未婚322人,占51.1%(P＜0.01)。