tbuckley/cabot-search huggingface dataset:
Tumor microenvironment associated with increased pretreatment density of activated PD-1+ LAG-3+/− TIM-3− CD8+ T cells facilitates clinical response to axicabtagene ciloleucel (axi-cel) in patients (pts) with large B-cell lymphoma.
Authors: Jerome Galon, Nathalie Scholler, Regis Perbost, Sarah Turcan, Corinne Danan, Frederick Lundry Locke, Sattva Swarup Neelapu, David Bernard Miklos, Caron A. Jacobson, Lazaros J. Lekakis, Yi Lin, Armin Ghobadi, Justin Chou, Zixing Wang, Allen Xue, John M. Rossi, Adrian Bot
Journal: Journal of Clinical Oncology (2020)

3022 Background: Axi-cel is a US and EU-approved autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy for pts with relapsed/refractory large B cell lymphoma after ≥ 2 prior therapies. In ZUMA-1 (NCT02348216), the objective response rate was 83% (58% complete response rate; Locke et al. Lancet Oncol. 2019). T cell-related biology (Immunosign 21; Immunoscore) measured pretreatment in the tumor microenvironment (TME) was associated with response to axi-cel (Rossi et al. AACR 2018. #LB-016; Rossi et al. AACR 2019. #CT153). This expanded analysis characterized the pretreatment TME immune contexture and examined associations between immune cell subsets and response. Methods: In ZUMA-1, pts received axi-cel at a target dose of 2.0 × 10 6 CAR T cells/kg. Archival pretreatment tumor biopsy samples were analyzed by multiplex immunohistochemistry (Brightplex). Two panels were developed and applied to assess T cell (CD3, CD8, FoxP3, PD-1, LAG-3, TIM-3) and myeloid cell (CD11b, CD14, CD15, LOX1, S100A9, CD68) subsets (n = 14 total). The association between T cell and myeloid cell subset density, prespecified immune scores (Immunosign 21; Immunoscore), and objective response was evaluated. T test values were based on Brightplex analysis. Results: Pretreatment tumor biopsy samples from 18 pts were analyzed (14 objective responders and 4 nonresponders). The pretreatment TME comprised all major myeloid and T cell subsets, with diverse distribution across samples analyzed. The median TME density of monocytes (CD11b+ CD15− CD14+; 1215 cells/mm 2 ) and macrophages (CD68+; 530 cells/mm 2 ) was greater than that of the total CD8+ T cell subset (312 cells/mm 2 ). The pretreatment Immunosign 21 and Immunoscore scores associated positively with the density of all major T cell subsets and some myeloid subsets. The density of activated CD8+ T cells (PD-1+ LAG-3+/− TIM-3−) was most significantly associated with clinical response versus other T cell subsets. The density of nonactivated CD8+ T cells (PD-1− LAG-3− TIM-3−) and exhausted CD8+ T cells (PD-1+ LAG-3+ TIM-3+) were not significantly associated with response. Additional characterization of the immune contexture and correlative analysis of cell subsets will be presented. Conclusions: These results suggest that a TME associated with increased density of activated PD-1+ LAG-3+/− TIM-3− CD8+ T cells, measurable pretreatment, facilitates clinical response in pts post–axi-cel.
Screening strategy for type 2 diabetes
Authors: 江孙芳, 高鑫
Journal: BMJ (2010)

糖尿病是威胁人类健康的主要疾病之一,其中2型糖尿病是最为主要的类型,在我国患病人群中2型糖尿病占93.7%[1].由于2型糖尿病起病隐匿,因此如何在人群中筛查2型糖尿病患者成为该疾病控制的重要手段之一。
Exomes and transcriptomes to reveal actionable findings in patients with negative-targeted panel sequencing.
Authors: Eric Y. Zhao, Jonathon Torchia, Alexander Fortuna, Dax Torti, Celeste Yu, Elizabeth Shah, Aoife McCarthy, Tracy Stockley, Peter Sabatini, John Bartlett, Lillian L. Siu, Philippe L. Bedard, Trevor John Pugh
Journal: Journal of Clinical Oncology (2020)

3562 Background: Next generation sequencing targeted panels increasingly inform clinical decisions, but may miss actionable findings detectable by whole exome sequencing (WES) and RNA-seq. There has been no direct comparison of WES plus RNA-seq against targeted panel sequencing to determine its added utility. To address this, we performed WES and RNA-seq analysis in a cohort of 100 patients with no actionable findings on prior panel sequencing. Methods: Ontario-wide Cancer Targeted Nucleic Acid Evaluation (OCTANE; NCT02906943) has sequenced 2,106 patients using a 161-gene Oncomine or 555-gene Hi5 panel. 100 patients (98 Hi5, 2 Oncomine) were chosen for further sequencing. Tumor (100x coverage) and normal (50x) exomes and tumor transcriptomes were sequenced on Illumina HiSeq2500 or NextSeq550. Interpretation included knowledgebase annotation (e.g. OncoKB, CIViC), mutation signatures, homologous recombination deficiency (HRD) scores, gene expression, and pathway analysis. Findings were deemed “actionable” if they could directly inform management or trial eligibility. Results: WES and RNA-seq identified one or more novel actionable findings in 38 patients. Of these, the main actionable finding was tumor mutation burden (TMB), mutation signature, or HRD score in 19 (50%), a copy number variant in 16 (42%), a fusion in 2 (5%), and a point mutation in 1 (2.6%). WES identified a MALAT1-GLI1 fusion in a cancer of unknown primary (CUP) whose transcriptome was consistent with gastric cancer, together suggesting the diagnosis of a rare gastroblastoma. To date, two cases have received exome-supported targeted therapy: (1) a metastatic high grade serous ovarian cancer, HRD-high, treated with olaparib then cisplatin for a combined 15 months, and (2) a metastatic neuroendocrine rectal tumor with RICTOR amplification treated with everolimus starting in Dec 2016 until last follow-up in Sep 2019. Of 62 patients with no actionable finding, expanded sequencing identified one or more known cancer drivers in 25 (40%): 17 CNVs, 3 fusions, and 5 point mutations or indels. In 16 patients, an oncogenic variant found on panel was not captured by WES, and may represent artifacts, germline mutations, or subclonal/localized variants. Conclusions: WES and RNA-seq expanded detection of actionable biomarkers and oncogenic mutations, especially CNV, TMB/signatures, and HRD. Two cases have undergone exome-supported targeted treatment. We performed the first WES of a rare gastroblastoma, originally a CUP but reclassified by expanded fusion detection and RNA-seq.
Clinical treatment of pressure ulcer in stagesII-IV
Authors: Jian-guo Zhang, Guang Yang, Jun Fan
Journal: BMJ (2013)

A total of 267 patients with pressure ulcer were randomly divided into treatment and control groups. All of them underwent traditional debridement. The wounds in treatment group were spreaded with traditional Chinese medicine. According to the results of bacteria culture and drug sensitivity, antimicrobial agents were selected in control group. The observation indices of two groups included pain grade, swelling grade, ulcer area and skin temperature difference. Then the variations of observation indices before and after treatment were examined. In treatment and control groups, the different values of pain grade before and after treatment were 2.1±0.9 and 1.2±0.7, swelling grade 1.3±0.6 and 0.7±0.5, ulcer area 4.7±3.1 and 2.4±2.5 and skin temperature difference 0.12±0.05 and 0.22±0.10 respectively. Treatment group was superior to control group and there was statistical significance (P<0.05). The effective rates were 95.6% and 65.4% and the number of cured patients 86 and 33 cases respectively. And there was statistical significance (P<0.05).


Key words: 
Skin ulcer; Chinese medical formula
Laparoscopic sentinel node navigation surgery versus laparoscopic standard gastrectomy with lymph node dissection in early gastric cancer: Final three-year survival results of multicenter randomized controlled phase III trial (SENORITA trial).
Authors: Keun Won Ryu, Young Woo Kim, Jae Seok Min, Ji Yeong An, Hong Man Yoon, Bang Wool Eom, Hoon Hur, Young Joon Lee, Gyu Seok Cho, Youngkyu Park, Mi Ran Jung, Ji-Ho Park, Woo Jin Hyung, Sang-Ho Jeong, Mira Han, Byung-Ho Nam
Journal: Journal of Clinical Oncology (2020)

4510 Background: The benefits and hazards of laparoscopic sentinel node navigation surgery (LSNNS), compared with laparoscopic standard gastrectomy (LSG) with lymph node dissection in early gastric cancer (EGC), are unknown. The SENORITA trial investigated the clinical impact of LSNNS in EGC in terms of short-term surgical outcomes, long-term survival and quality of life. Methods: This study is a prospective, multicenter, randomized controlled, non-inferiority trial. Patients with preoperatively diagnosed gastric adenocarcinoma with T1N0 of 3 cm or less in diameter, regardless of histology, except absolute indication for endoscopic resection were eligible. Patients were randomized to LSG or LSNNS using dual tracers. The primary endpoint is 3-year disease-free survival (3yDFS). Planned sample size per arm is 290 patients with the non-inferiority margin of 2.737 in hazard ratio (HR) assuming that LSG achieve 97% 3yDFS, 5% of type 1 error and 80% of power. Three-year recurrence-free survival (3yRFS), overall survival (3yOS) and disease specific death rate (3yDSDR) were evaluated as secondary endpoints. Results: From March 2013 to December 2016, 580 patients were randomized (LSG arm 292 vs. LSNNS arm 288). After 53 patients dropped out before surgery, operation was performed in 527 patients (269 vs. 258), representing the full analysis set. LSG was performed in 266 according to the protocol excluding 3 open conversion. After exclusion of 13 without LSNNS due to various reasons, LSNNS was performed in 245 patients according to the protocol. After median follow up of 47.5 months, 3yDFS were 95.5% and 91.8% (HR 1.901, CI 0.911 – 3.967), respectively. The 3yRFS was 98.9% and 95.2% (p=0.019), and 3yOS was 99.2% and 97.6% (p=0.166), and 3yDSDR was 99.5% and 99.1% (p=0.591), respectively. Conclusion: LSNNS in EGC did not show non-inferiority compared with LSG in terms of 3yDFS. However, 3yOS and 3yDSDR of LSNNS were comparable to LSG by the rescue surgery of recurrence. LSNNS might be an alternative surgical option instead of LSG in selected EGC patients. Clinical trial information: NCT01804998 .
伪差性室性心动过速误诊一例
Authors: 田智华
Journal: BMJ (2006)

患者女,60岁,因发作性胸闷于2004年3月15日在外院行动态心电图检查.检查中记录到2段成串的宽大畸形R波(图1),被诊断为室性心动过速,转入本院进一步诊治.询问病史患者在记录到所谓室性心动过速的相应时段里,有跑步下楼梯、骑自行车去银行、在银行取钱等活动,均无心悸胸闷或其他不适.入院后行冠状动脉造影检查未见异常.通过静脉插入电极导管反复进行心室刺激也未能诱发出室性心动过速.分析该心电图可见到一串酷似尖端扭转型室性心动过速形态的宽大畸形R波.但是仔细观察会发现窦性心律引起的正常形态的QRS(图1箭头处),所有相邻两窦性QRS波群的间距均为1 109 ms.故由该图伪差性室性心动过速的诊断明确。
Effect of PSA on equal treatment of high-risk patients.
Authors: Basil Ferenczi, Jason Frankel, Nathan Jung, Christopher Porter, John Paul Flores
Journal: Journal of Clinical Oncology (2020)

e17514 Background: National Comprehensive Cancer Network (NCCN) guidelines recommend definitive treatment for high risk prostate cancer (HRPCa). This study aims to assess treatment trends for men with HRPCa, focusing on men deemed high risk on the basis of an elevated PSA alone with otherwise low risk features. Our hypothesis is that this group is treated differently than other patients with high risk disease. Methods: The National Cancer Database (NCDB) prostate cancer (PCa) participant use file was queried for high risk patients ages 18-75 with biopsy proven PCa from 2010-2016. The NCDB represents approximately 55% of men treated for PCa in the United States. Patients were divided into two groups: the study group with PSA &gt; 20 and otherwise low risk features, and a comparison group comprised of high-risk patients due to cT stage ≥T3a or Gleason Grade Group ≥4. Patients with nodal or metastatic disease were excluded. Rates of treatment by modality were compared over the years studied. Survival was modeled using Kaplan Meier analysis. Results: 91,565 patients met eligibility criteria with 12,156 in the study group and 79,409 in the comparison group (Table). In the study group, a significantly higher number of patients underwent surveillance (10.2%) versus the comparison group (0.3%)(p &lt; 0.001). Furthermore, there was an upward trend in use of surveillance in the study group, with a surveillance rate of 18.9% in 2016. Amongst patients receiving radiation, only 26.1% received androgen deprivation therapy (ADT) in the study group versus 82.8% in the comparison group. Despite these findings, survival analysis demonstrated significantly higher 5-year overall survival in the study group (95.1%) vs the comparison group (87.8%) (HR = 0.41, p &lt; 0.001). Conclusions: Men categorized as HRPCa by PSA alone with otherwise low risk features are treated less aggressively than other high-risk patients with significantly higher rates of surveillance and radiation without ADT. However, these men appear to have better survival outcomes than other high-risk patients at 5-year follow-up. [Table: see text]
Clinical analysis of 230 cases of drug-induced liver injury
Authors: Yi-jin Zhang, Fang Qian, Wei Ling, Mei-mei Tian, Xiao-di Guo, Ying Fan, Yun-ru Li, Xiao-ling Fan
Journal: BMJ (2013)

Objective
To review the clinical features of acute drug-induced liver injury.


Methods
The clinical data of 230 patients with acute drug-induced liver injury admitted to Beijing Ditan Hospital from October 2005 to May 2011 were retrospectively analyzed.


Results
In 230 patients, more than 60% had symptoms of fatigue, anorexia, jaundice and liver damage presenting LT, AST, ALP and TBIL changes. The hepatocellular injury type accounted for 80.4% (185/230), cholestatic type accounted 11.7% (27/230) and mixed type accounted for 7.8% (18/230). Chinese herbal medicine or Chinese patent medicine was the most common cause of drug-induced liver injury (55.2%), followed by anti-TB drugs (9.6%) and other anti-bacterial drugs (5.2%). There were 218 cases (94.7%) with favorable prognosis and 12 cases (5.3%) with poor prognosis, including 4 aggravating cases discharged against medical advance and 8 deaths.


Conclusion
The lack of gold standard for the diagnosis of drug-induced liver injury may easily lead to misdiagnosis. Chinese Traditional medicine, anti-TB drugs and other anti-microbial drugs are main causes of drug-induced liver injury. Early detection and timely treatment are important for the management of drug-induced liver injury.


Key words: 
Retrospective studies; Drug-induced liver injury; Clinical features
Tissue factor pathway inhibitor II as a specific biomarker for pre-operative prediction of clear-cell carcinoma of the ovary.
Authors: Etsuko Miyagi, Noriaki Arakawa, Naho Ruiz Yokota, Takeharu Yamanaka, Kentaro Sakamaki, Yohei Miyagi, Satoshi Yamaguchi, Shoji Nagao, Yuki Yamada, Yasuyuki Hirashima, Yuka Kasamatsu, Hisamori Kato, Masakazu Kitagawa, Hiroshi Kobayashi
Journal: Journal of Clinical Oncology (2020)

e18077 Background: Tissue factor pathway inhibitor 2 (TFPI2) is a novel serum biomarker that discriminates ovarian clear cell carcinomas (CCC) from borderline ovarian tumors (BD) and non-CCC epithelial ovarian cancers (EOC). We examined the prediction performances of TFPI2, including high specificity, for preoperative diagnosis of CCC in multi-center settings. Methods: We collected serum samples obtained preoperatively from patients with ovarian masses who needed surgical treatment to confirm pathological diagnoses in five hospitals in Japan. The diagnostic powers of serum levels of TFPI2 (cutoff value 270 pg/mL) and CA125 (cutoff value 35 U/mL) to discriminate CCC from BD, non-CCC-EOC, and benign lesions were compared. Results: A total of 351 patients (77 ovarian benign lesions, 65 BD and 209 EOC including 69 CCC) were analyzed. Serum TFPI2 levels were significantly higher in CCC patients (mean±SD, 508.2±812.0 pg/mL) than in patients with benign lesions (154.7±46.5), BD (181±95.5) and non-CCC EOC (265.4±289.1). TFPI2 had a high diagnostic specificity to CCC (sensitivity and specificity: 43.5% and 79.5%, respectively). The sensitivity of TFPI2 was improved to 71.1% when combined with CA125, and it was increased in Stage II–IV CCC (66.7%) compared with Stage I CCC (33.3%). In patients with benign endometriotic cysts (BEM), no patient was positive for TFPI2 but 71.4% (15/21) were CA125 positive. TFPI2 showed good performance in discriminating Stage II–IV CCC from BD and non-CCC EOC patients (AUC 0.815 for TFPI2 versus 0.505 for CA125) or from BEM (AUC 0.957 for TFPI2 versus 0.748 for CA125). Conclusions: High specificity of TFPI2 for the preoperative detection of CCC was re-verified with the defined cutoff level of TFPI2 in practice. TFPI2 and CA125 may have a substantial contribution to the precise prediction of intractable CCC. [Table: see text]
Latent Class Trajectory Modeling of 2‐Component Disease Activity Score in 28 Joints Identifies Multiple Rheumatoid Arthritis Phenotypes of Response to Biologic Disease‐Modifying Antirheumatic Drugs
Authors: Arianna Dagliati, Darren Plant, Nisha Nair, Meghna Jani, Beatrice Amico, Niels Peek, Ann W. Morgan, John Isaacs, Anthony G. Wilson, Kimme L. Hyrich, Nophar Geifman, Anne Barton
Journal: Arthritis & Rheumatology (2020)

Objective To determine whether using a reweighted disease activity score that better reflects joint synovitis, i.e., the 2‐component Disease Activity Score in 28 joints ( DAS 28) (based on swollen joint count and C‐reactive protein level), produces more clinically relevant treatment outcome trajectories compared to the standard 4‐component DAS 28. Methods Latent class mixed modeling of response to biologic treatment was applied to 2,991 rheumatoid arthritis ( RA ) patients in whom treatment with a biologic disease‐modifying antirheumatic drug was being initiated within the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate cohort, using both 4‐component and 2‐component DAS 28 scores as outcome measures. Patient groups with similar trajectories were compared in terms of pretreatment baseline characteristics (including disability and comorbidities) and follow‐up characteristics (including antidrug antibody events, adherence to treatments, and blood drug levels). We compared the trajectories obtained using the 4‐ and 2‐component scores to determine which characteristics were better captured by each. Results Using the 4‐component DAS 28, we identified 3 trajectory groups, which is consistent with previous findings. We showed that the 4‐component DAS 28 captures information relating to depression. Using the 2‐component DAS 28, 7 trajectory groups were identified; among them, distinct groups of nonresponders had a higher incidence of respiratory comorbidities and a higher proportion of antidrug antibody events. We also identified a group of patients for whom the 2‐component DAS 28 scores remained relatively low; this group included a high percentage of patients who were nonadherent to treatment. This highlights the utility of both the 4‐ and 2‐component DAS 28 for monitoring different components of disease activity. Conclusion Here we show that the 2‐component modified DAS 28 defines important biologic and clinical phenotypes associated with treatment outcome in RA and characterizes important underlying response mechanisms to biologic drugs.
Application of invasive and non-invasive sequential ventilation in severe chronic obstructive pulmonary disease
Authors: Jie Li, Hong-dong Zhao, Ping Wang
Journal: BMJ (2011)

Twenty four patients of chronic obstructive pulmonary disease complicated with severe respiratory failure were divided into two groups randomly: sequential ventilation group and control ventilation group (n = 12 in each group). Patients in sequential group received invasive ventilation at beginning, once the pulmonary infection control window (PICW) reached the trachea cannula was extubated immediately replaced by Bi-level positive airway pressure( BiPAP) noninvasive ventilation with oral-nasal mask; while in control ventilation group the invasive ventilation was continued using pressure support ventilation (PSV) until stopping mechanical ventilation. The total ventilation time, the invasive ventilated time,the length of stay in hospital,monitoring time and the incidence rate of ventilation associated pneumonia (VAP) were evaluated in two groups. The total ventilation time [(7. 8 ±2. 5 ) d, (12 ±2. 2) d], the invasive ventilated time [(4. 9 ±2. 2)d, and (12 ± 2. 2) d] the length of hospital stay [(8. 5 ± 2. 5 ) d, (13 ± 2. 6) d] in the sequential ventilation group were significantly shorter than those in the control ventilation group (P ＜ 0.05); the incidence rate of VAP was lower than that in the control group. The results indicates that sequential ventilation with the guidance of PICW can shorten the total ventilation time, the critical monitoring time and the length of hospital stay, it can also reduce the incidence of VAP and improve the prognosis of patients.

Key words: 
Respiratory, artificial;  Pulmonary disease, chronic obstructive
Trastuzumab deruxtecan for HER2-positive metastatic breast cancer: DESTINY-Breast01 subgroup analysis.
Authors: Shanu Modi, Fabrice Andre, Ian E. Krop, Cristina Saura, Toshinari Yamashita, Sung-Bae Kim, Kenji Tamura, Shuquan Chen, Fumitaka Suto, Yusuke Kuwahara, Caleb C. Lee, Yeon Hee Park
Journal: Journal of Clinical Oncology (2020)

1036 Background: Trastuzumab deruxtecan (T-DXd; DS-8201) is an antibody-drug conjugate composed of an anti-HER2 antibody, a cleavable linker, and a cytotoxic topoisomerase I inhibitor. In the pivotal DESTINY-Breast01 trial, efficacy of T-DXd in HER2-positive metastatic breast cancer (mBC) was demonstrated, with an objective response rate (ORR) of 60.9% and median progression-free survival (mPFS) of 16.4 months. Methods: DESTINY-Breast01 was a single-group, open-label, multicenter, phase II trial of 184 patients with HER2-positive mBC previously treated with trastuzumab emtansine (T-DM1) who received T-DXd at 5.4 mg/kg. Multivariate analysis using logistic regression models (ORR) and Cox proportional hazards models (duration of response [DOR], mPFS) explored 15 relevant clinical predictor variables. Circulating tumor DNA (ctDNA) was collected prior to the first dose, every 3 cycles of treatment, and at the end of treatment. Sequencing was done via GuardantOMNI (Guardant Health) for single-nucleotide variation/insertion and deletion, amplification, and fusion of ≈ 500 genes. Results: Efficacy in all evaluated clinical subgroups was similar to the overall ORR 60.9% and mPFS 16.4 months with ranges from ORR 46.4%-74.5% and mPFS 12.3-18.1 months. Variables associated with improved ORR, DOR, or mPFS included hormone receptor positive status, fewer prior treatment regimens (continuous variable), pertuzumab given in the first or second line, and normal renal and hepatic function. Variables that did not impact efficacy outcomes compared to the overall population include age, race, region, ECOG PS, HER2 IHC 3+ status, progesterone receptor status, best response to T-DM1, time since diagnosis, and history of brain metastases. In 48 subjects with progression as of data cut date, metastases were most commonly observed in the liver, lung, and lymph nodes. Only 8% (4 of 48) had progression involvement in the brain upon disease progression. Decrease of ERBB2 copy number in ctDNA was seen on treatment and correlated with clinical response. Additional changes in molecular markers on treatment and following progression will be described. Conclusions: T-DXd demonstrated strong efficacy in all clinical subgroups analyzed. Further exploration of both clinical and molecular variables to determine biomarkers of efficacy may be warranted. Clinical trial information: NCT03248492 .