tbuckley/cabot-search huggingface dataset:
Clinical features of non-Hodgkin's lymphoma in cheek misdiagnosed as inflammatory myopathy
Authors: Yang Jiao, Xiaoming Huang, Yu Wang, Qian Wang, Wen Zhang, Jialin Chen, Xuejun Zeng
Journal: BMJ (2017)

Objective
To assess the clinical features of non-Hodgkin's lymphoma in cheek misdiagnosed as inflammatory myopathy.


Methods
Six patients presenting with unilateral swollen cheek were admitted at the Department of General Internal Medicine, Peking Union Medical College Hospital between January 2010 and December 2014. These patients were misdiagnosed as inflammatory myopathy and finally confirmed as Non-Hodgkin's lymphoma. The clinical characteristics, findings of laboratory tests and the diagnostic procedures were retrospectively analyzed.


Results
The median age of 6 patients (3 males and 3 females) was 30 years.The median duration from onset of unilateral swollen cheek to the final diagnosis was 13 months; the patients were referred to average 4 hospitals and experienced average 3 biopsies before admission. All patients had been treated with prednisone at a dose of 1 mg/kg or 0.5mg/kg per day. However, the symptoms relapsed in all patients after glucocorticoid tapering. No patient presented with proximal muscle weakness or myalgia. Two of 6 patients presented with unilateral forearm swollen. Creatine kinase was mildly elevated in 3 patients. Electromyographic abnormalities were seen in 4 patients. The biopsy showed muscle fiber necrosis, degeneration and a large amount of lymphocytes infiltration with or without vessel wall involvement. Erythrocyte sedimentation rate and high-sensitive C-reactive protein levels were normal. Anti-Jo-1, ANA and anti-U1RNP were all negative. EBV-DNV was significantly elevated in peripheral blood in 5 patients and it was positive in biopsy specimen in 3 patients. PET-CT scan was performed in 3 patients and suggested high metabolic activity with a SUV of 2.0-8.5 in cheek region. The biopsy specimen taken before admission did not show evidence of lymphoma. Repeated biopsies from cheek regions (3/6), lips (2/6) and forearm confirmed the final diagnosis as Non-Hodgkin's lymphoma, including 2 cases of T-cell lymphoma and 4 cases of NK/T cell lymphoma.


Conclusion
When patients present with unilateral swollen cheek without proximal skeletal muscle weakness or myalgia, even the pathologic evaluation implies inflammatory myopathy, non-Hodgkin's lymphoma should be considered. Repeated biopsy may be necessary to confirm the diagnosis.


Key words: 
Myositis; Lymphoma, non-Hodgkin; Diagnostic errors
Combined regimen of inhalable STING agonist plus chemoimmunotherapy in platinum-resistant or platinum-refratory ovarian cancer: A randomized, open-label, phase II trial.
Authors: Yan Zhang, Qian Mei, Yuanguang Meng, Meixia Chen, Yang Liu, Qingming Yang, Weidong Han
Journal: Journal of Clinical Oncology (2020)

6071 Background: Approximately 70% patients with advanced ovarian cancer have a relapse and ultimately succumb to their disease. Treatment options are limited in this context with an unacceptable low response (less than 20%). Immunotherapy with checkpoint inhibitors presented to date are not very convincing with 10-15% response because of inadequate immunity. We previously discovered the critical role of manganese in innate immune sensing of tumors by activating STING signaling. This ongoing, randomized, phase II study is to assess STING agonist plus nPP chemotherapy and anti-PD-1 antibody sintilimab in platinum-resistant/refractory ovarian cancer. Methods: Enrolled patients were 2:1 randomizedly assigned to receive nab-paclitaxel (180-220mg/m 2 ), cisplatin (60-80mg/m 2 ) and sintilimab 200mg per 3 weeks with (cohort 1) or without (cohort 2) inhalable MnCl 2 (0.4mg/kg) daily. Safety was assessed by CTCAE v5.0, and clinical response by MRI or CT every 2 cycles referred to RECIST version 1.1. The primary endpoints were objective response rate (ORR) and safety. Key secondary end points were disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Results: 27 patients were enrolled, and 21 were included in efficacy population by the end of Jan. 2020. All enrolled patients were with heavily treated history, median 4 lines of prior therapy, median 19 cycles of multiagent regimens. The addition of MnCl 2 to the combined chemo-immunotherapy did not appear to exacerbate treatment-related adverse events (AEs). The most common AEs are hematological toxicity (87%), nausea (56%) and vomiting (47%) in both two cohorts. All 14 evaluable patients (14/19) from cohort 1 had an effective control (11 PR [78.6%], 3 SD [21.4%]) . Ten patients (71.4%) achieved PR at the first tumor scan assessment. For 8 cases from cohort 2, 7 were assessable and all showed SD, 4 of whom exhibited SD with enlarged lesions and disease progression after 4-cycle treatment. Conclusions: MnCl 2 administration induced encouraging objective clinical responses (78.6%) and disease control (100%) in relapsed/refractory ovarian cancer. The combined regimen showed accepted and manageable safety profile. Clinical trial information: NCT03989336.
CICERO: a versatile method for detecting complex and diverse driver fusions using cancer RNA sequencing data
Authors: Liqing Tian, Yongjin Li, Michael N. Edmonson, Xin Zhou, Scott Newman, Clay McLeod, Andrew Thrasher, Yu Liu, Bo Tang, Michael C. Rusch, John Easton, Jing Ma, Eric Davis, Austyn Trull, J. Robert Michael, Karol Szlachta, Charles Mullighan, Suzanne J. Baker, James R. Downing, David W. Ellison, Jinghui Zhang
Journal: Genome biology (2020)

Abstract To discover driver fusions beyond canonical exon-to-exon chimeric transcripts, we develop CICERO, a local assembly-based algorithm that integrates RNA-seq read support with extensive annotation for candidate ranking. CICERO outperforms commonly used methods, achieving a 95% detection rate for 184 independently validated driver fusions including internal tandem duplications and other non-canonical events in 170 pediatric cancer transcriptomes. Re-analysis of TCGA glioblastoma RNA-seq unveils previously unreported kinase fusions (KLHL7-BRAF) and a 13% prevalence of EGFR C-terminal truncation. Accessible via standard or cloud-based implementation, CICERO enhances driver fusion detection for research and precision oncology. The CICERO source code is available at https://github.com/stjude/Cicero .
Prognostic significance of Musashi 2 (MSI2) RNA-binding protein expression in precancerous polyps and during colorectal cancer (CRC) progression.
Authors: Leonid Kharin, Nikolay S. Karnaukhov, Mark Voloshin, Anton G. Milakin, Igor Bychkov, Alexander Deneka, Elena M. Frantsiyants, Oleg Ivanovich Kit, Erica Golemis, Yanis Boumber
Journal: Journal of Clinical Oncology (2020)

e16009 Background: The RNA-binding protein Musashi-2 (MSI2) controls the translation of proteins that support stem cell identity and lineage determination. Elevated expression of MSI2 plays an important role during progression, dissemination, and drug resistance in numerous solid and hematological malignancies. This study assessed MSI2 as potential clinical biomarker in colorectal cancer (CRC) and pre-malignant disorders of colon mucosa. Methods: This study included 125 patients, of whom 20 had tubulovillous adenomas (TAs) of the colon, and 105 had verified colorectal cancer. Of the 105 patients with CRC, 45 had locoregional invasion (stages I-III). The remaining 60 patients had liver metastases (mCRC), with 31 patients diagnosed with synchronous and 29 with metachronous metastases. We used immunohistochemical (IHC) approach to measure MSI2 expression in matching specimens of normal versus TA tissues, normal versus primary CRC tumor, and normal versus metastatic CRC, followed by correlative analysis in relation to clinical outcomes. In parallel, the biological effects of overexpressing or depleting MSI2 expression in human CRC cells were analyzed in vitro using qRT-PCR, western blot, proliferation and clonogenic assays. Results: MSI2 expression in patient samples was significantly elevated in TAs versus primary tissue (p &lt; 0.002), and was further elevated in primary tumor, and in metastatic sites (p &lt; 0.0001 versus normal tissue, p &lt; 0.003 versus TAs). MSI2 expression positively correlated with decreased progression free survival (PFS) and overall survival (OS), lower tumor grade, and right-side localization (p = 0.004) of tumors. In vitro knockdown of MSI2 in CRC cells suppressed of proliferation, survival and clonogenic capacities of the cells. Conclusions: Elevated expression of MSI2 is associated with pre-cancerous polyps (TAs) in the colonic mucosa, indicating it is an early event in transformation. MSI2 is further elevated during, CRC progression, and associated with poor prognosis, and loss of MSI2 reduces multiple growth properties of CRC cell models. These data imply a causative role of MSI2 overexpression at multiple stages of CRC formation and progression.
Head-to-head comparison of the non-G-CSF small molecule single agent (SA) plinabulin with SA pegfilgrastim for the prevention of docetaxel chemotherapy (chemo)-induced neutropenia (CIN) in the protective-1 trial.
Authors: Douglas W. Blayney, Lan Huang, Ramon W. Mohanlal
Journal: Journal of Clinical Oncology (2020)

TPS7087 Background: Plinabulin (Plin) is a small molecule with anti-cancer activity and CIN effects. The Phase (Ph) 2 clinical trial NPI-2358-101 ( NCT00630110 ) evaluated Plin at 20 or 30 mg/m2 on Day (D) 1 and D8) plus D1 Docetaxel (Doc) 75 mg/m2 combination versus D1 Doc alone in patients (pts) with non-small cell lung cancer(NSCLC). In a large ( &gt; 70%) subset of pts with a measurable lung lesion in the lung (per RECIST 1.1) receiving 30 mg/m2 Plin + Doc (n = 38), mOS was 4.6 months longer vs Doc alone (n = 38) (Mohanlal ASCO-SITC 2018). An unexpected post-hoc finding was a CIN benefit with adding at 20 or 30 mg/m2 Plin to Doc: 33% of pts in the Doc arm had grade 4 neutropenia, whereas in the Plin +Doc group 4% of pts (P &lt; 0.0003) (Blayney ASH 2018). Plin boost the number the number of hematopoietic/progenitor cells in bone marrow. We subsequently initiated two global Ph3 programs with Plin: 1. A Ph 3 trial confirming its anticancer activity in NSCLC (study BPI-2358-103; NCT02504489; this trial is ongoing) and 2. An evaluation of Plin for CIN prevention through studies BPI-2358-105 (NCT03102606; PROTECTIVE-1), and study 106 (NCT03294577; PROTECTIVE-2). We previously reported from the Ph 2 portion of study 105, that SA Plin and Pegfigrastim (Peg) had comparable protection against CIN induced by Doc, however in contrast to Peg, Plin did not cause bone pain or thrombocytopenia (Blayney IASLC 2018, ESMO 2018). Plin is given by 30 min IV infusion on the same day of Chemo, 30 min after Chemo. The Ph3 portion of Study 105 in ongoing. Methods: In the Ph 3 portion of PROTECTIVE-1, pts with NSCLC, HRPC or BC are randomized (1:1) to either Plin 40 mg (over 30 minutes on D1; n = 75) or Peg 6mg (on D2, n = 75), and the primary endpoint is Duration of Severe Neutropenia (DSN). Plin 20 mg/m2 is similar to a 40 mg fixed dose. Absolute neutrophil counts (ANC) is determined on D 0, 1,2,3,6,8,9,10, 15 in Cycle 1 The trial aims to demonstrate non-inferiority of Plin vs Peg. Non-inferiority will be declared if the non-inferiority margin (NIM) of 0.65 day will be met, which NIM is more conservative than the 1 day NIM, typically employed for G-CSG biosimilar trials. Pts should have at least 1 risk factor as per NCCN guidelines.The trial is double-blinded to enable reliable PRO, Bone Pain and QoL assessments through validated questionnaires (EQ-5D-5L; EORTC QLQ-C30; Wang Baker Faces Pain Rating Scale). Following an Interim Analysis, the trial will continue without modifications. Clinical trial information: NCT03102606 .
心脏介入性治疗并发急性和亚急性心脏压塞的早期识别和急诊处理
Authors: 潘宜智, 李广镰, 罗义, 曾冲, 冯开薇, 刘震, 雷晓明
Journal: BMJ (2006)

回顾性总结8例心脏介入治疗并发急性和亚急性心脏压塞患者的临床资料.8例年龄9～85岁,于介入性治疗术中出现急性心脏压塞3例,在术后延迟出现亚急性心脏压塞5例.其中行起搏器植入术2例,临时心脏起搏2例,冠状动脉介入治疗3例,右心室造影1例.均行心包穿刺及留置引流导管治疗,抢救成功7例,死亡1例.提示心脏介入性治疗合并急性和亚急性心脏压塞多与操作不当有关,应加强防范意识,改进操作技巧;心脏压塞的早期识别和果断处理是成功抢救患者的关键。
The impact of the metastasis region on patients with metastatic renal cell cancer in the intermediate-risk group.
Authors: Cengiz Karacin, Fatma Bugdaycı Basal, Irem Bilgetekin, Omur Berna Oksuzoglu
Journal: Journal of Clinical Oncology (2020)

e17091 Background: The majority of patients with metastatic renal cell carcinoma (mRCC) are in the intermediate-risk group, according to International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). Some patients in the intermediate-risk group have similar overall survival (OS) with those in the good-risk group, while others with those in the poor-risk group. In our study, we aimed to evaluate the prognostic significance of the region of the metastasis and to classify the intermediate-risk group into two as favorable or unfavorable according to the metastasis region. Methods: We retrospectively analyzed the clinical data of patients with mRCC those in the intermediate-risk group seen at our Oncology Training and Research Hospital from 2010 to 2018. Patients who received at least one line of tyrosine kinase inhibitor (TKI) were included in the study. Overall survival was calculated. The log-rank test was used to check the statistical significance for OS. Results: Of 113 patients, median age 58 (range 34-78) years, 99 (88%) had more than one site of metastasis: 61 (54%) lung, 41 (36%) bone, 21 (18%) lymph node, and 19 (17%) brain metastasis. Nine patients received one, 86 patients received two, and 18 patients received three lines of systemic therapy. Median follow up was 14 (range 4 – 54) months. Median OS for patients with bone and/or brain metastasis was 10 (95% CI = 6.1 – 13.9) months compared to 16 (95% CI = 10.1 – 22.2) months for patients with lung and/or lymph node metastasis (HR = 1.675, p-value = 0.012). Conclusions: Our data suggest that the bone and/or brain metastasis in the intermediate-risk group mRCC patients treated with TKI are unfavorable prognostic factors.
Outcomes with reduced intensity therapy in a low-risk subset of children with National Cancer Institute (NCI) standard-risk (SR) B-lymphoblastic leukemia (B-ALL): A report from Children’s Oncology Group (COG) AALL0932.
Authors: Reuven J. Schore, Anne J. Angiolillo, John A Kairalla, Meenakshi Devidas, Karen R. Rabin, Patrick A Zweidler-McKay, Michael J. Borowitz, Brent L. Wood, Andrew J Carroll, Nyla A. Heerema, Mary V. Relling, Johann Hitzler, Ashley R. Lane, Kelly W. Maloney, Cindy Wang, William L. Carroll, Naomi J. Winick, Elizabeth A. Raetz, Mignon L. Loh, Stephen Hunger
Journal: Journal of Clinical Oncology (2020)

10509 Background: Post-hoc analysis of COG P9904 identified a low risk (LR) group of SR B-ALL patients aged 1-9.99 years with WBC &lt; 50,000/µL, no CNS3, and either ETV6/RUNX1 or double trisomies (DT) of chromosomes 4 and 10 with day 8 peripheral blood (PB) and day 29 marrow (BM) minimal residual disease (MRD) &lt; 0.01% who had a 5-year event-free survival (EFS) of 97±2% and overall survival (OS) 98.8±0.8%. Outstanding results were also obtained for LR patients on COG AALL0331 using CCG-based ALL therapy. AALL0932 tested prospectively whether LR B-ALL patients could attain a 5-year EFS ≥95% with these regimens. Methods: Following a 3-drug induction, eligible AALL0932 LR patients had NCI SR B-ALL (no testicular leukemia, unfavorable genetics or Down syndrome) with DT or ETV6/RUNX1 fusion, CNS1, no steroid pre-treatment, with Day 8 PB and Day 29 BM MRD &lt; 0.01%. Between 2010-16, 603 LR patients were randomized to P9904-based regimen LR-M (n = 301) or CCG 1991/COG AALL0331-based regimen LR-C (n = 302). LR-M included 6 24-hour infusions of 1 gm/m 2 of methotrexate (MTX) with leucovorin rescue, but no anthracyclines or alkylating agents. Maintenance followed with daily 6-mercaptopurine (6-MP) and weekly oral MTX, and every 16 week 7-day pulses of dexamethasone (DEX) with vincristine (VCR) on days 1 and 8. Boys and girls were treated for 2.5 years from diagnosis. LR-C had no 24-hour MTX infusions, but included 2 Interim Maintenance (IM) phases with VCR and escalating IV MTX without leucovorin rescue given every 10 days for 5 doses, flanking an 8-week Delayed Intensification (DI) phase that included DEX, VCR, pegasparagase, doxorubicin (75 mg/m 2 ), cyclophosphamide (1 gm/m 2 ) and 8 doses of low-dose cytarabine (75 mg/m2/dose). LR-C Maintenance included daily 6-MP and weekly oral MTX with 5-day pulses of DEX and 1 dose of VCR given every 12 weeks. Girls received 2 years and boys 3 years of therapy from the start of IM I. Results: Both regimens achieved outstanding outcomes: 5-yr disease-free survival (±SE) 98.8%±0.8% for LR-M and 98.5%±0.9% for LR-C (p = 0.67). Both had 5-yr OS 100%. Therapies were well tolerated with higher rates of mucositis (12.9 vs 6.3%; p = 0.008) and allergic reactions (2.3% vs 0%; p = 0.02) on LR-C. Conclusions: AALL0932 demonstrated that application of stringent risk criteria can identify a favorable B-ALL subgroup almost certain to be cured with either LR-M or LR-C, allowing physicians and families to select the optimal treatment approach in the future. Clinical trial information: NCT01190930.
抑郁症的识别与治疗
Authors: 叶尘宇, 王立伟
Journal: BMJ (2007)

随着上个世纪70年代健康新定义的提出以及医学模式的转变,人们逐渐改变了对精神卫生问题讳疾忌医的态度,越来越重视心理健康.抑郁症正逐渐成为现代社会的关键词之一.美国的一项调查显示,普通人群平均5%患有抑郁症。
Arthroscopic-assisted diagnosis and treatment in osteochondral fracture at external condyle of femur with the miniature incision
Authors: Da-gang Zhang, Zhang-yun Deng, Zhao-yang Hu, Hong-lin You, Bo Hu, Chuan-cheng Pu
Journal: BMJ (2010)

Eight patients with osteochondral fracture of femur condyle were diagnosed and treated with arthroscopic-assisted miniature incision, the osteochondral fracture blocks were fixed with the absorbable rod. All patients were followed-up for 8 to 12 months (mean 10 months). The score of Lysholm scale of the knee function in preoperation was 42 ± 4, that in postoperation was 87 ± 6; the movement range of the knee joint in preoperation was (78 ± 13)°, that in postoperation was (125 ±9)°. The results indicate that arthroscopic-assisted surgery with the miniature incision for the treatment of osteochondral fracture in external condyle of femur has the advantages of minimal trauma, less complication, well functional recovery and the comprehensive recovery of knee joint function.

Key words: 
Fracture, carti lage;  Arthroscopy
Association of leukocyte count (neutrophilia and lymphopenia) with poor prognosis in patients with high-grade gliomas in a Guatemalan cohort.
Authors: Rixci Ramirez, Daniel Estuardo Rosales Lopez, Jennifer Dominguez, Marisol Gramajo, Carolina Camey
Journal: Journal of Clinical Oncology (2020)

e14500 Background: In previous studies separately, it has already been determined how the inflammatory response measured by it neutrophilia and also lymphopenia s with temozolamide have determined that they are important at the time of initiation of treatment and have a prognostic value in patients with high-grade gliomas, the objective This study was the prognostic value of leukocyte disorders, absolute neutrophil count and absolute lymphocyte count in a retrospective cohort of patients with high-grade glioma who receive concomitant temozolomide and radiation plus maintenance. Methods: Clinical records of patients treated at the Guatemalan Social Security Institute were registered in the Oncology service within the period from January 1, 2013 to December 2018, the treatment consisted of temozolomide (75 mg / m2 per day) and concomitant radiation and subsequent maintenance with temozolomide (150 mg / m2 D1-5) every 28 days for 6 cycles. The prognostic value of neutrophilia and lymphopenia, prior to treatment in survival, was defined as a neutrophil count greater than 7x10 3 / uL and lymphopenia less than 2 x10 3 / uL. The analysis was performed using Kapplan Mayer curves, log rank test and Cox analysis. Results: We identified 64 high-grade patients (grades III and IV according to WHO), all treatments with concomitant chemoradiotherapy based on temozolomide and subsequent maintenance with temozolamide. The initial surgery was lost in the majority (75%), with resection &gt; 90% in 25 patients (34%). 79.4% were treated with radiotherapy plus concomitant chemotherapy followed by adjuvant chemotherapy with temozolamide of these, 69% completed the treatment, thirty-two patients (50%) with pre-treatment neutrophilia. The overall survival at 2 years was 55%. In the univariate analysis, neutrophilia is associated with a worse overall survival (p = 0.019), as well as lymphopenia (p = 0.003), in addition to the age ≥65 years (p = 0.0001), surgical resection &lt; 90% (p = 0.045) and prednisolone consumption ≥50mg / day (p = 0.045). In the multivariate analysis, neutrophilia (p = 0.017), age ≥65 (p = 0.001), lymphopenia (p = 0.0056) were associated with a worse prognosis with reduced survival. Conclusions: In high-grade gliomas treated with temozolomide and concomitant radiation followed by maintenance with temozolamide, neutrophilia and lymphopenia can be a significant prognostic factor for overall survival, with the advantage that it is not an expensive test and is accessible at all times of patient follow-up.
Impact of immunotherapy use in patients with stage IV biliary carcinoma.
Authors: Mariajose Rojas, Takefumi Komiya, Neil R. Sharma, Emily Powell
Journal: Journal of Clinical Oncology (2020)

e16597 Background: Most patients with cholangiocarcinoma have non resectable disease at the time of diagnosis and usually die within 6-12 months. The 5-year survival rate is very low (about 5%), and since most patients present with advanced disease at time of diagnosis, treatment includes chemoradiation and biliary stenting. Recently, trials with immunotherapy (IO) for treatment of advanced cancer have shown promising results as alternative therapeutic options. Despite indications in other solid tumors, the role of IO is unknown for biliary cancer. Methods: Using National Cancer Database (NCDB), cases of Stage IV biliary cancers (including gallbladder and cholangiocarcinoma) diagnosed in the period of 2014-2016 with at least 30-day follow up were analyzed. The following clinical demographics were included: age (younger than 70 vs. older than 70), sex (male vs. female), race (whites vs. others), insurance (uninsured vs. insured), liver metastasis (Yes vs. No). We also analyzed data regarding cancer treatment, including radiation (Yes vs. No), chemotherapy (Yes vs. No), and IO (Yes vs. No). Survival analysis was performed using Kaplan-Meier curves and Log-rank tests. A p-value &lt; 0.05 was considered significant. Results: Among 6,344 eligible cases, 57 patients were treated with IO. No significant association between use of IO and clinical demographics was observed except for use of chemotherapy (p = 0.001) and primary location (gallbladder vs. others, p = 0.042). Chemotherapy was administered in 52 (91%) and 4112 (65%) of cases in IO and non-IO groups, respectively. Use of IO was associated with improved overall survival in both univariate and multivariate analyses (p = 0.0005and 0.0156, respectively). Median overall survival (in months) was 14.0 in the IO group vs 7.0 in the non-IO group. Landmark analysis in the IO group showed 12 and 24-month survival of 56.1% and 19.3% respectively, as compared with 27.8% and 7.6% in the non-IO group. Conclusions: This retrospective data analysis using a large cancer database suggests that use of IO could improve survival in patients with advanced biliary cancer. More studies will be needed in the future to validate these results.