tbuckley/cabot-search huggingface dataset:
Treatment outcomes and healthcare resource utilization (HRU) among patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy in US community oncology setting.
Authors: Roger M. Lyons, Jalaja Potluri, Cat Bui, Michelle E Choi, Esprit Ma, Anders Svensson, Kalatu Davies, Srinivas Annavarapu, Tatyana Kapustyan
Journal: Journal of Clinical Oncology (2020)

e19513 Background: Treatment options for AML patients ineligible for intensive chemotherapy are limited. This study aims to describe demographic and clinical characteristics, outcomes, and HCRU in this patient population. Methods: This was a retrospective observational study of patients aged &gt; 60 years who received first-line (1L) treatment within 60 days of AML diagnosis between 1/1/2011 – 1/1/2018 and had &gt; 2 visits at US Oncology Network (USON) clinics. Patients were followed until 6/30/2018, last visit, or death, whichever came first. Data were sourced from structured fields of the USON database and chart reviews. Patient characteristics and HRU were assessed using descriptive statistics while overall survival (OS), time-to-treatment failure (TTF), and progression-free survival (PFS) from 1L treatment initiation were assessed using the Kaplan-Meier method. Results: 378 patients were included with median age of 79 years; 62.7% were male, 29.3% had an ECOG score &gt; 2, and 38.4% had poor cytogenetic risk profile. Most patients received 1L hypomethylating agent (HMA) monotherapy: azacitidine (AZA, 57.9%) or decitabine (DEC, 25.9%). Few patients received best supportive care only (7.1%) or other AML treatment (9.1%). Median (range) durations of 1L treatment among patients receiving AZA and DEC were 2.9 (0.0, 46.9) and 2.5 (0.1, 26.4) months, respectively. Median (95% CI) OS, TTF, and PFS in the AZA and DEC cohorts were 7.5 (5.7, 9.6) and 7.3 (4.8, 8.8) months, 3.4 (2.8, 4.4) and 3.7 (2.4, 5.2) months, and 6.7 (5.0, 8.0) and 5.7 (3.4, 7.4) months, respectively. Among patients receiving HMAs, 84.5% received at least one transfusion. Median number of red blood cell and platelet transfusions was 4.0. Hospitalization rates in the AZA and DEC cohorts were 79.9% and 83.7%; proportions with hospitalization &gt; 2 days duration were 64.4% and 66.3%, respectively, with median (range) durations of 6.5 (3.0, 34.0) and 7.0 (3.0, 26.0) days, respectively. Conclusions: The low TTF and OS and high HRU in this real-world community oncology study indicates an unmet need to improve outcomes among AML patients ineligible for intensive chemotherapy. NCCN guidelines were updated since this study and future real-world studies are warranted to evaluate impact of novel therapies on treatment patterns and outcomes.
Etiology and clinical features of acute pancreatitis in young patients
Authors: Wei Tan, He-sheng Luo, Jun Yan, Yu Chen, Hong Xia
Journal: BMJ (2011)

Objective To investigate etiology and clinical features of acute pancreatitis (AP) in young patients. Methods In total, 423 patients with AP admitted to Renmin Hospital of Wuhan University, Wuhan, Hubei province during January 2006 to December 2009 were retrospectively analyzed, 55 cases aged 34 years or less as young group and another 55 cases aged more than 34 years as middle- and elderly-age group. Their etiology, clinical features and illness scores based on some standard criteria were assessed. Results Proportion of varied etiologies of AP in young group was different from that in middle- and elderly-age one (x2 = 17. 107, P = 0. 009) , mainly as biliary and idiopathic pancreatitis in young group and as biliary and alcoholic pancreatitis in middle- and elderly-age one. Incidence of diet-related and idiopathic pancreatitis were higher in young group than that in middle- and elderly-age one ( x2 =4. 853, P = 0. 028 and x2=4. 274, P = 0. 039 ). Scores of the acute physiology and chronic health evaluation II ( APACHE II ) , Ranson criteria and the bedside index for severity in acute pancreatitis ( BISAP) were all lower in young group than those in middle- and elderly-age one (t = 5. 381 , P = 0. 000; t = 4. 388 , P = 0. 000 and t=3. 083, P = 0. 003 ) . There was no statistically significant difference in scores of computed tomography severity index ( CTSI) between young group and middle- and elderly-age one (t = ±0. 750, P > 0. 05 ) . Recurrence rate of AP was lower in young group than that in middle- and elderly-age one ( x2 =4. 251, P = 0. 039). Cholecystitis was more complicated in young group, pregnancy was more complicated in young group (x2 =4. 151 , P =0. 042) , and elevated blood glucose was more complicated in middle- and elderly-age one (x2 = 13. 285 , P = 0. 000 ) . Conclusions Etiology of AP varies in young patients with more dietary factors, occurrence of systemic complications and risks for death are lower in young group than those in middle- and elderly-age one, and there was no statistically significant difference in local complications and severity of illness between the two groups.

Key words: 
Youth; Pancreatitis; Retrospective studies
阵发性室上性心动过速不同类型的心电图表现
Authors: 张海澄, 昃峰
Journal: BMJ (2009)

阵发性室上性心动过速(paroxysmal supraventricular tachycardia,PSVT)是临床常见的快速心律失常之一,患病率约为2.25‰,在人群中的发病率约为每年35/10万,患者通常无器质性心脏病的表现,不同性别与年龄均可发病.其中房室结折返性心动过速(atrioventricular nodal reentranttachycardia,AVNRT)和房室折返性心动过速(atrioventricular reciprocating tachycardia,AVRT)是PSVT最常见的两种类型,占PSVT的90%以上,其他少见的类型还包括阵发性房性心动过速等。
RelB silencing to reverse tamoxifen resistance by regulating GPx4 and ferroptosis in breast cancer.
Authors: Zhi Xu, Jinhai Tang
Journal: Journal of Clinical Oncology (2020)

e12513 Background: Tamoxifen(Tam), as an essential therapeutic treatment of estrogen receptor(ER)-positive breast cancer(BCa), has been available for the past three decades. However, the induction of Tam resistance during therapy has indicated a significant challenge with regards to this agent. Tam could increase oxidative stress and induce cell death by regulating reactive oxygen species(ROS). Ferroptosis, a cell death process driven by the accumulation of iron-dependent lipid peroxides, has been induced by inactivation/depletion of glutathione peroxidases(GPxs). Our previous studies found that the expression level of RelB gene, a member of NF-κB family, is negatively correlated with ER targeted by Tam in BCa. Methods: The RelB level of BCa tumor tissues and the corresponding cell lines were examined by immunoblotting and western blot. The effects of Tam on cell viability were determined using colony survival and MTT assay. The ROS and oxygen consumption rates(OCR) were measured using specific ROS detection probes and a Seahorse XF96 Analyzer, respectively. The lipid peroxidation level of cells was analyzed by immunofluorescence assay. The morphological changes of mitochondria were observed by transmission electron microscope. RelB binding to the NF-κB intronic enhancer region of the human GPx4 gene was determined using a ChIP assay. Accordingly, the effect of RelB on BCa Tam resistance was further validated using BCa mice xenograft models. Results: RelB was uniquely expressed at the high level in Tam resistance BCa tissues and cell lines. Down-regulation of RelB based on a CRISPR/Cas9 system remarkably sensitized resistance BCa cells to Tam. Treatment with SN52, a RelB inhibitor, illuminated the role of RelB in Tam-treated BCa cells. The high level of ROS and declination of mitochondrial respiration which induced by Tam were inhibited in resistance cells. Tam enhanced lipid peroxidation with concomitant non-apoptotic cell death, which are negatively regulated by GPx4 activity. In addition to GPx4 knockdown, deferoxamine was able to rescue Tam-induced cell death in BCa cells, verifying that Tam induces cell death partially through ferroptosis. Importantly, RelB upregulates GPx4 expression through binding to an NF-κB enhancer element located at the 5’-flanking region. Consistently, in vivo functional validation confirmed that RelB inhibition not only impairs tumor growth, but also inhibits Tam resistance in nude mice. Conclusions: RelB could inhibit ferroptosis which induced by hydroxyl radicals accumulation through upregulating GPx4 in BCa.
Camrelizumab (Camre) plus taxane-based chemotherapy (CT): Clinical outcomes and dynamic monitoring of CEA as a predictive biomarker of response in patients with recurrent or advanced esophageal squamous cell carcinoma (ESCC).
Authors: Cheng Kong, Jianhua Xu, Ming Jiang, Xiangzhi Zhu, Jinjun Ye, Shaorong Yu, Jun Zhu
Journal: Journal of Clinical Oncology (2020)

e16524 Background: Keynote-181 study reported anti-PD-1 antibody pembrolizumab as monotherapy had shown superior efficacy compared to CT for previously treated patients (pts) with advanced ESCC. The combination of anti-PD-1 antibody and CT may be a feasible approach to provide antitumor activity superior to either agent alone. However, the available data about the combination strategy is limited. Methods: We retrospectively reviewed the records of pts treated at our center to identify pts seen between 7/2019 and 12/2019 with recurrent or metastatic ESCC who received treatment with Camre (anti-PD-1 antibody) plus taxane-based CT. The primary endpoints were objective response rate (ORR) and disease control rate (DCR) per RECIST 1.1. Secondary endpoint included toxicity. The carcinoembryonic-antigen (CEA) dynamics and clinical associations were also evaluated in the selected pts. Results: A total of 14 pts were identified. The median age was 66 years (44-80). Most pts were male (12/14, 85.7%) with metastatic disease (10/14, 71.4%). The CT regimens contained nab-paclitaxel in 4 pts, nab-paclitaxel plus nedaplatin in 2, liposomal paclitaxel in 2, liposomal paclitaxel plus nedaplatin in 6. Camre in combination with CT were repeated every 3 to 4 weeks for up to 4 cycles. Two pts also received maintenance therapy of Camre for 4 and 6 cycles. Five pts (35.7%) exhibited a best overall response of PR, 6 (42.9%) SD, and 3 (21.4%) PD. The ORR and DCR were 35.7% (5/14) and 78.6% (11/14), respectively. All the SD determination as the best response met the minimum interval of 8 weeks from baseline. Toxicity profile was mild with mainly grade 1, expected toxicities. The most common grade 3/4 adverse events were leucopenia (2/14, 14.3%) and neutropenia (2/14, 14.3%). CEA baseline levels were normal in 6 cases, elevated in 8. It was observed that CEA levels closely paralleled overall measurable tumor burdens in all the CEA-elevated pts. A patient with equivocal radiographic pseudoprogression even had CEA dynamics that correlated with eventual clinical outcome. Conclusions: We identified a group of pts of recurrent or metastatic ESCC treated with Camre plus taxane-based CT and achieving a favorable DCR to therapy with a tolerable toxicity profile. This combination regimen warrants further exploration in a prospective clinical trial. CEA dynamics may be a useful tool to monitor disease evolution in this setting.
Drugging the undruggable: A market readiness analysis for KRAS-G12C.
Authors: Fotios Loupakis, Kenneth Joel Bloom, Wendy Allen, Enya Scanlon, Isabel Stacey, Derry Mae Keeling, Nital Patel, Jordan Clark
Journal: Journal of Clinical Oncology (2020)

e15667 Background: KRAS G12C is a distinctively aggressive, poor survival, tumor genotype conferring resistance to anti-EGFR therapies in lung, colorectal (CRC) and pancreatic cancers. Prospective therapies targeting G12C have demonstrated promising activity in Phase I trials. In the advent of potentially transformative novel inhibitor therapies, we assess the need for earlier and repeated tumor profiling between treatments to accurately guide further therapeutics and assess market readiness for specified testing. Methods: Treatment-naïve patients and cell-lines were assessed for genomic change by consensus molecular classification in CRC pre/post treatment with standard chemotherapy. Assessing mutation occurrence, prevalence and testing rates, we aimed to identify areas of translational potential for testing within common cancers. A laboratory and prescriber mapping of the US across lung, CRC and pancreatic cancer types, was carried out using Diaceutics’ proprietary Global Diagnostics Index (GDI), a real-world data diagnostic database, to determine market readiness for companion diagnostic (CDx) and follow-on testing in the dawn of transformative therapies. Potential barriers to test adoption were explored including reimbursement analysis. Results: Genomic analysis shows CRC tumors change after treatment with first-line therapies rendering the primary tumor profile result less reliable. This highlights a distinct need for repeated testing post-treatment for continued efficacy in therapeutics. Patients with pancreatic cancer would benefit the most from increased testing for G12C particularly earlier testing as KRAS mutants occur before neoplastic transformation. Although the market appears ready, reimbursement for KRAS G12C remains a challenge for pancreatic cancer compared to either lung or CRC. Conclusions: This study provides genomic evidence of the necessity for more frequent tumor testing post-treatment with chemotherapy, and earlier testing in pancreatic cancer to enhance efficacy of targeted therapies. The market is ready for increased testing volumes, yet problems surrounding reimbursement and stage of testing remain. Earlier testing may increase survival and decrease cost of patient care, suggesting more frequent testing is imperative across cancer types.
Follow-up survey on psychological health status in persons bit by dogs
Authors: Bao-long Zhao
Journal: BMJ (2010)

Objective To investigate psychological health status and its change in short term among persons bit by dogs.Methods Psychological health status was evaluated with patient health questionnaire (PHQ-15) Chinese version for the 613 wounded persons bit by dogs,including 368 males and 245 females with average age of 36 years plus or minus 14 years (standard deviation),meanwhile their wounds were handled routinely at clinics,as well as health education and cognitive psychological intervention were provided for them.Results All of the 613 persons with dog bites had mild or moderate somatic syndrome in their initial visits and 478 of them (78.0%) still presented mild somatic syndrome and only 23 (3.7%)with moderate symptoms four week after dog bites by PHQ-15 scores.One hundred and fifty-two of 613 (24.8%) followed-up at their initial visits had depressive symptoms,which could remain in 61 of them (10.0%) four weeks after bites.Two hundred and eighty-four of them (46.3%) had anxiety symptoms at initial visits,and 258 (42.1%) still had mild and nine (1.5%) had moderate symptoms four weeks after bites.Conclusions Psychological symptoms were popular in wounded persons by dog bites,which can persist for a certain time.PHQ-15 can be used for evaluating their psychological status.

Key words: 
Bite and stings;  Neuropsychological tests;  Questionnaires
24 h esophageal pH monitoring in patients with gastroesophageal reflux-induced cough treated with omeprazole
Authors: Li-ping Zou, Jie-ping Yu, He-sheng Luo
Journal: BMJ (2009)

To monitor the 24 h esophageal pH in patients with gastroesophageal reflux-induced cough (GERC) before and after omeprazole treatment. Methods The prospective study was conducted in Department of Gastroenterology, People's Hospital of Wuhan University from February 2007 to April 2008. Twenty patients with GERC received 40 mg of omeprazole daily and underwent 24 h esophageal pH monitoring before and 8 weeks after omeprazole treatment. Six parameters by Johson and Demeester were adopted for evaluation: pereentage of total time with pH <4, percentage of uptight reflux time with pH <4, percentage of supine reflux time with pH < 4, the number of reflux episodes with pH < 4, the number of reflux episodes longer than 5 min and the percentage of longest reflux duration. Results The values of six parameters before treatment were 13.5±8.5, 12.2±4.0, 15.8 ±4.1, 56 ± 13, 4. 15 ± 1.87 and 26.2 ± 16. 5 respectively; while those after treatment were 2.7± 1.3, 3.9 ± 1.9, 1.9 ± 1.0, 18 ± 11, 1.24 ±0.65 and 7.4 ± 2. 1. There were significant differences in these six parameters between pre-treatment and post-treatment (P<0.01 ). Conclusion The 24 h esophageal pH monitoring shows that omeprazole is effective in treatment of GERC by decreasing esophageal pH.

Key words: 
Gastroesophageal reflux;  Cough ;  pH;  Omeprazole
Comprehensive gene expression analysis of IDH1/2 mutant biliary cancers (BC).
Authors: Francesca Battaglin, Joanne Xiu, Yasmine Baca, Jia Zeng, Anthony Frank Shields, Richard M. Goldberg, Andreas Seeber, Diane Habib, Alberto Puccini, Ryuma Tokunaga, Hiroyuki Arai, Jingyuan Wang, Martin D. Berger, Igor A. Astsaturov, Albert Craig Lockhart, Wu Zhang, John Marshall, Wolfgang Michael Korn, Heinz-Josef Lenz, Anthony B. El-Khoueiry
Journal: Journal of Clinical Oncology (2020)

4598 Background: Isocitrate dehydrogenases (IDH) mutations (mut) identify a distinct subtype of BC that has yet to be fully characterized. We recently showed that IDH1/2 mutant (mIDH) BC harbor specific gene alterations involving chromatin remodeling and DNA repair, and a differential immune markers profile compared to other mIDH GI tumors. Here we aim to further dissect the molecular profile of mIDH BC through a comprehensive gene expression profiling analysis. Methods: 524 BC samples (303 intrahepatic cholangiocarcinoma, IHCC, 67 extrahepatic cholangiocarcinoma, EHCC, 141 gallbladder, 13 unspecified) collected between February to December of 2019 were included. Samples were analyzed using NextGen DNA sequencing (NextSeq, 592 gene panel), whole transcriptome RNA sequencing (NovaSeq) and immunohistochemistry (Caris Life Sciences, Phoenix, AZ). EBseq was used to identify differentially expressed genes in mIDH vs wild type (WT) tumors with control for FDR ( Q &lt; 0.2). Pathway and functional enrichment analysis was performed using g:Profiler and Enrichr. Results: mIDH frequency in our cohort was 11.4% (60/524), with higher prevalence of IDH1 mut (8.8%). IHCC showed the highest mut prevalence: IDH1 13.5%, IDH2 4.6%. mIDH was more common in females ( P = 0.0036). A total of 774 genes were significantly differentially expressed between mIDH and WT: 582 underexpressed (Fold change, FC: 0.025~0.699); 192 overexpressed (FC: 1.43~3.3). Pathway enrichment showed a significant decrease of gene expression in cytokine-cytokine receptor interaction ( Q = 0.002) and inflammatory response genes ( Q = 0.005) in mIDH. Interferon-γ- and PD1 signaling-related genes expression was significantly lower in mIDH vs WT ( Q = 0.02) including IFNG (FC 0.32), NKG7 (FC 0.36), CD8B (FC 0.37), BATF (FC 0.40), PD1 (FC 0.53), SLAMF6 (FC 0.55) and PD-L2 (FC 0.60). Wnt and cadherin signaling were also enriched for altered expression in several genes in mIDH BC ( Q = 3.86e-7 and &lt; 0.00001, respectively). Conclusions: To our knowledge, this is the largest and most extensive gene expression profiling study focused on mIDH BC. Our data show for the first time a distinct gene expression profile characterizing mIDH tumors which display significant downregulation of inflammatory response pathways and immune-related genes. These findings contribute to further the understanding of mIDH BC and may inform the future development of rational combination therapies.
Treatment failure pattern of oropharyngeal cancer, especially for the aspect of retropharyngeal lymph node.
Authors: Byung-Hee Kang, Jin Ho Kim, Hong-Gyun Wu, In Ah Kim, Keun-Yong Eom
Journal: Journal of Clinical Oncology (2020)

e18565 Background: In radiotherapy for head and neck cancer, it is very important to define the appropriate treatment volumes that determine the treatment outcome and toxicity. We examined the feasibility of omitting elective retropharyngeal (RP) nodal irradiation in oropharyngeal cancer. Methods: We performed a retrospective review from 2009 to 2016; 197 patients with oropharyngeal squamous cell carcinomas were treated with definitive or postoperative radiation therapy at the Seoul National University Hospital or Seoul National University Bundang Hospital. Of these patients, 151 patients (76%) were treated ipsilateral RP nodal areas up to the upper edge of C1 vertebral body, while the other 46 patients (24%) were not. We reviewed patterns of failures, disease free survival, and patient-reported chronic xerostomia status in each patient group. Results: During follow-up period, 2 patient developed RP nodal recurrences (4-108 months, median =46 months). There was no significant between-group difference in disease free survival, with a rate of 80.7% in the high RP nodal-irradiation group and 87.2% in the RP nodal spared group (P=0.17). Patients in the high RP nodal-irradiation group had higher mean ipsilateral parotid gland dose (median 28.7±7.5 Gy vs. 21.3±7.6 Gy, P&lt;0.001) and higher rates of chronic xerostomia (72.2% vs. 58.7%, P=0.030). Conclusions: Only 2 patients with omission of high RP node irradiation developed high RP node failure, and no significant difference in DFS was shown. Omission of high RP nodal irradiation resulted in reduced ipsilateral parotid gland dose, consequently with less chronic xerostomia.
Ecto-NTPDase CD39 is a negative checkpoint that inhibits follicular helper cell generation
Authors: Wenqiang Cao, Fengqin Fang, Timothy Gould, Xuanying Li, Chulwoo Kim, Claire Gustafson, Simon Lambert, Cornelia M. Weyand, Jörg J. Goronzy
Journal: Journal of Clinical Investigation (2020)

Vaccination is a mainstay in preventive medicine, reducing morbidity and mortality from infection, largely by generating pathogen-specific neutralizing antibodies. However, standard immunization strategies are insufficient with increasing age due to immunological impediments, including defects in T follicular helper (Tfh) cells. Here, we found that Tfh generation is inversely linked to the expression of the ecto-NTPDase CD39 that modifies purinergic signaling. The lineage-determining transcription factor BCL6 inhibited CD39 expression, while increased Tfh frequencies were found in individuals with a germline polymorphism preventing transcription of ENTPD1, encoding CD39. In in vitro human and in vivo mouse studies, Tfh generation and germinal center responses were enhanced by reducing CD39 expression through the inhibition of the cAMP/PKA/p-CREB pathway, or by blocking adenosine signaling downstream of CD39 using the selective adenosine A2a receptor antagonist istradefylline. Thus, purinergic signaling in differentiating T cells can be targeted to improve vaccine responses, in particular in older individuals who have increased CD39 expression.