tbuckley/cabot-search huggingface dataset:
Optimizing management of glioblastoma: Educational impact on clinicians.
Authors: Michelle Arielle Worst, Ann Carothers, Kinjal Parikh, Lisa Brauer, Giuseppe Lombardi, Timothy Francis Cloughesy
Journal: Journal of Clinical Oncology (2020)

11026 Background: Glioblastoma multiforme (GBM) is a rare, malignant tumor of the central nervous system (CNS) with poor prognosis. Nearly all patients experience recurrence due to GBM’s heterogeneity and there is currently no standard approach to treatment. Despite having few targeted agents with demonstrated efficacy, molecular testing is utilized due to its value in improving diagnostic accuracy and prognostic stratification. Moreover, recent data has shown an increase in promising data with regards to treating GBM using various mechanisms. Because of the clinical conundrum GBM poses and the lack of available treatment options, clinicians are challenged to stay current with new data and how best to integrate new agents into treatment paradigms. The objective of this study was to assess the changes in oncologists’ and pathologists’ knowledge through participation in education regarding optimal GBM treatment. Methods: The educational activity was a 30-minute online, video discussion segmented into 3 parts with synchronized slides and 2 faculty. Educational effect was assessed with a repeated pairs pre-/post-assessment study with a 3-item, multiple choice, knowledge questionnaire and one confidence assessment question. For all questions, each participant served as his/her own control. Pre- and post-assessment scores were compared to determine the relative changes in the proportion of correct responses. A chi-square test assessed statistical significance at the P &lt; 0.05 level. The activity launched 26 th June 2019; data were collected until 19 th August 2019. Results: Overall significant improvements were seen after education for oncologists (N = 62, P &lt; .001) and pathologists (N = 67, P &lt; .01). The relative improvement was 67% for oncologists and 45% for pathologists (pre-/post-assessment average correct response rates were 30%/50% and 29%/42%, respectively). Following the activity, 55% of oncologists and 51% of pathologists had a measurable improvement in confidence in their ability to differentiate among late-stage investigational agents for GBM based on mechanism of action. Conclusions: Participation in an online, CME intervention consisting of a series of video discussions, totaling 30-minutes, resulted in statistically significant improvements in knowledge and confidence of oncologists and pathologists, that may lead to improvements in clinical care. As new data and agents emerge, new educational activities are necessary to reinforce knowledge, close persistent gaps, and increase oncologists’ and pathologists’ confidence in this clinical setting.
Clinicopathological analysis of langerhans cell histiocytosis
Authors: Qiupeng Wang, Yijian Yu, Jiaochen Wang, Shouxiang Weng
Journal: BMJ (2014)

The clinicopathological data of 13 patients with Langerhans cell histiocytosis (LCH) from January 2004 to January 2014 were retrospectively analyzed.There were 8 males and 5 females with a mean age of 35(6-63)years. For all 13 cases, there were 15 lesions. Histologically, there was a diffuse distribution of Langerhans cells accompanied by a variable number of eosinophils and some other inflammatory cells. Immunohistochemical study showed tumor cells were positive for S-100 protein, CD1a and Langerin. During a follow-up period of 6-101 months, all survived. The diagnosis of LCH was assisted by immunophenotypic analyses for S-100, CD1a and Langerin. Combination therapy was effective. Most patients had an excellent prognosis.


Key words: 
Lymphoproliferative disorders; Langerhans cell
ER, PR, and HER2 expression in Ugandan breast cancer patients: An evaluation of in-country RT-PCR compared to IHC.
Authors: Manoj Menon, Jackson Orem, Scott Adams, Alex Bakenga, Diana Basemera, David Kasozi, Eric Quentin Konnick, Kelvin Mubiru, Yusuf Mulumba, Catherine Muwonge, Lazarus Okoche, Robert Pierce, Julie Gralow, Nixon Niyonzima
Journal: Journal of Clinical Oncology (2020)

e19009 Background: Breast cancer, the most common cancer in sub-Saharan Africa (SSA), is characterized by poor survival. An accurate assessment of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 receptor (HER2) status, typically via immunohistochemistry (IHC), is considered essential to provide prognostic data and guide therapeutic decision-making. However, due to inaccessible IHC services, these data are often unavailable in many parts of SSA; alternate methods need to be explored. Given the lab infrastructure developed in response to the HIV pandemic, RT-PCR testing is more readily accessible and feasible in SSA. Here we assess the potential of RT-PCR in evaluating the receptor status of women with breast cancer in Uganda. Methods: We enrolled women with a new diagnosis of invasive breast cancer at the Uganda Cancer Institute. Demographic and clinical data were obtained. A formalin-fixed paraffin embedded (FFPE) specimen was utilized for quantitative RT-PCR, using a validated assay for the detection of the ER, PR and HER2. Receptor expression levels were expressed as relative quantity (RQ) compared to housekeeping genes (CALM2). HER2 IHC results were categorized as negative (score 0 or 1+) or positive (3+); 2+ results (n=6) were excluded as FISH testing was not performed. Unstained slides were sent to the Fred Hutchinson Cancer Research Center for IHC. Receiver operating characteristic (ROC) analysis was applied to compare RT-PCR to IHC (gold standard). Results: We analyzed interim data (anticipated N=100 of an ongoing study) from 32 women aged 35 to 56 years. The majority of women (25, 78%) presented with advanced stage disease. Of the 32 cancers, 18 were ER+ (56%), 10 were PR+ (31%), 9 were HER2+ (28%) and 8 were triple negative (25%) by IHC. From ROC analysis, the AUC were 0.94, 0.95, and 0.81 for ER, PR, and HER2 respectively with high sensitivity and specificity (Table). Conclusions: Despite the tremendous need, the ability to detect the ER, PR, and HER2 via IHC in SSA is limited. Here we demonstrate the favorable test characteristics of RT-PCR when compared to IHC. Given the relatively wide accessibility of RT-PCR and endocrine therapy for breast cancer, as well as the recent inclusion of trastuzumab in the WHO’s Essential Medicines List, the results of this study have both direct diagnostic and therapeutic implications. Clinical trial information: NCT03518242 . [Table: see text]
血糖控制良好的老年2型糖尿病患者动态血糖监测分析
Authors: 张敏, 陈树, 窦畅, 李凤琼
Journal: BMJ (2005)

为了解老年2型糖尿病患者的血糖控制效果和反应,对30例血糖控制良好的老年2型糖尿病患者进行动态血糖监测.结果显示22例患者发生低血糖,多发生在夜间,且发作时多数没有自觉症状.15例患者存在餐后高血糖。
Community-acquired pneumonia treated by ticarcillin sodium and davulanate potassium in elderly patients with cerebrovascular sequelae
Authors: Shi-qi Yin, Dian-fa Li
Journal: BMJ (2009)

Eighty-six patients with community-acquired pneumonia who suffered from cerebrovascular sequelae were admitted to hospital from 2005 to 2007.Patients were randomized into ticarcillin sodium/clavulanate potassium group and cefuroxime Sodium group.Sputum culture was performed for each case before and after treatment.Gram-negative bacilli accounted for 74%of infection,and the most common pathogens were klebsiella pneumoniae(26%)and Escherichia coli(14%).The response rates in two groups were 93%and 72%,respectively(χ2=6.54,P＜0.05).Bacteria eradication rates in two groups were 90%and 62%,respectively(χ2=6.00,P＜0.05).Ticarcillin sodium and clavulanate potassium is an effective antibiotic for community-acquired pneumonia in elderly patients with cerebrovascular sequelae.

Key words: 
Pneumonia; Ticarcillin
Information forfirst-visit psychology outpatients in general hospital
Authors: Jie Zhang, Lin-yong Hu
Journal: BMJ (2008)

：This study was toanalyze 1400 first-visit psychology outpatients from 8 May 2004 to 30 June 2007 inZhangzhou Hospital,Fujian Medical University.Our results showed that of all theparticipants,the following patients were more commonly seen:female,teenagers or mid-ageless than 50,and lower education level.Regarding to mental diseases,hysteria,seriousstress disorders or adjustment disorder,and neurosis were the leading diagnosis,followedby mood disorder,schizophrenia or other psychosis disorders,and apparatus psychosisdisorders.
Results of ENCORE 602 (TRIO025), a phase II, randomized, placebo-controlled, double-blinded, multicenter study of atezolizumab with or without entinostat in patients with advanced triple-negative breast cancer (aTNBC).
Authors: Joyce O'Shaughnessy, Rebecca L. Moroose, Sunil Babu, Kakhaber Baramidze, David Chan, Stuart P. Leitner, Gia Nemsadze, Peter Ordentlich, Christine Quaranto, Michael L. Meyers, Valeria González Graf, Taunya J. Smith, Valerie Bee-Munteanu, Rodrigo Fresco, Dennis J. Slamon
Journal: Journal of Clinical Oncology (2020)

1014 Background: Chemotherapy remains as the only standard treatment option for aTNBC in second and subsequent lines. Entinostat (ENT) is an oral, class I-selective histone deacetylase inhibitor, that has shown antitumor activity in preclinical models of TNBC when combined with immune checkpoint blockade. ENCORE 602 evaluated the efficacy and safety of atezolizumab (ATEZO) + ENT vs ATEZO + placebo (P) in patients (pts.) with pretreated aTNBC. Methods: Pts. with previously treated aTNBC (PD-1/PD-L1 inhibitors naïve) were randomized 1:1 to receive ATEZO (1200 mg IV Q3W) + ENT (5 mg PO QW) or ATEZO+P. Treatment continued until unequivocal progressive disease or unacceptable toxicity. The primary endpoint was PFS as determined by the investigators using RECIST 1.1. The hypothesis was that the combination would improve median PFS by 3 months (hazard ratio = 0.57). Sixty events (from 70 pts.) would provide 80% power with 1-sided significance level of 0.1. Secondary endpoints were PFS per immune-related RECIST (irRECIST), ORR, clinical benefit rate (CBR), Overall Survival (OS), and safety. Results: 81 pts. were enrolled, median age 56 years (range 29-87), 69% received 1 prior line of therapy and 31% &gt; 1 line. No significant difference in PFS per RECIST 1.1 was observed between ATEZO+ENT and ATEZO+P (median PFS 1.68 and 1.51 months, respectively [p = 0.64; HR 0.89, 95% CI: 0.53-1.48]), nor in any of the secondary efficacy endpoints (median PFS per irRECIST 1.68 vs 1.54 months; ORR 10.0% vs 2.4%; CBR 37.5% vs 31.7%; median OS 9.8 vs 12.4 months, respectively). Frequency of treatment-emergent adverse events (TEAEs), SAEs, discontinuations due to TEAE and TEAE with outcome death were higher in the ENT+ATEZO arm. Conclusions: In pts. with previously treated aTNBC, median PFS was not prolonged when ENT was added to ATEZO compared to ATEZO and placebo, and the combination resulted in greater toxicity. Clinical trial information: NCT02708680 .
A phase Ib study of the safety and pharmacology of nilotinib to prevent paclitaxel-induced peripheral neuropathy in patients with breast cancer.
Authors: Elizabeth J. Adams, Maryam B. Lustberg, Yan Jin, Yang Li, Alex Sparreboom, Shuiying Hu
Journal: Journal of Clinical Oncology (2020)

TPS12128 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating adverse effect of paclitaxel, but convincing evidence for a preventative technique founded on mechanistic rationale is lacking. We previously report that paclitaxel accumulation is mediated by the murine organic anion transporting polypeptide, OATP1B2 in mice (OATP1B1 and OATP1B3 in humans) (Leblanc, J Clin Invest, 2018). We found that paclitaxel induces acute and chronic neurotoxicity in mice in an OATP1B2-dependent manner, which is reversed by pre-treatment with FDA-approved tyrosine kinase inhibitor, nilotinib. Methods: This phase Ib dose finding study of nilotinib in combination with weekly paclitaxel is investigating the hypothesis that intermittent dosing of nilotinib 24 hours before paclitaxel infusion (excluding C1D1) and again 30 minutes before paclitaxel infusion will inhibit OATP1B1 and prevent CIPN. This hypothesis will be assessed using an adaptive Bayesian method for dose finding based on efficacy-toxicity trade-offs in patients with breast cancer stages I-III who qualify for paclitaxel therapy. Patients with previous ≥ grade 2 neuropathy on breast cancer therapies will be excluded. The primary objectives are to find the recommended phase II dose of nilotinib in combination with paclitaxel for early stage breast cancer, defined as the lowest intermittent dose of nilotinib that temporarily inhibits OATP1B1 function without affecting paclitaxel plasma pharmacokinetics (PK), and to determine the toxicity profile of nilotinib in combination with paclitaxel. OATP1B1 inhibition by nilotinib will be assessed via validated surrogate endogenous substrates, glycochenodeoxycholate sulfate (GCDGA-S) and chenodeoxycholate-24-glucuronide (CDCA-24G). Effective OATP1B1 inhibition will be ≥5-fold increase in AUC of GCDCA-S from pre- to post- treatment or detectable CDCA-24G levels post-treatment. The 4 nilotinib dose levels are 50 mg (dose level -1), 100 mg (dose level 1), 200 mg (dose level 2), 300 mg (dose level 3). IV paclitaxel dose of 80 mg/m 2 on D1,8,15 for 12 total weekly doses will be used. Oral nilotinib will be administered 24 hours before paclitaxel infusion on C1D7,D14 and again 30 minutes before infusion on C1D8,D15. Secondary objectives are to determine paclitaxel’s effect on PK of nilotinib and vice versa. Quality of life via CIPN-20 survey, disease free survival, event free survival, overall survival are exploratory objectives. NCT04205903 enrollment opened February 2020 and is accepting patients. Clinical trial information: NCT04205903 .
Renomedullary Interstitial Cell Endothelin A Receptors Regulate BP and Renal Function
Authors: Chunyan Hu, Jayalakshmi Lakshmipathi, Deborah Stuart, Janos Peti-Peterdi, Georgina Gyarmati, Chuan-Ming Hao, Peter Hansell, Donald E. Kohan
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement The functional significance of renomedullary interstitial cells, which are uniquely and abundantly expressed in the renal inner medulla, is largely unknown. In vitro studies have demonstrated that endothelin A receptors regulate multiple aspects of renomedullary interstitial cell function. Using a novel mouse model with inducible renomedullary interstitial cell–specific endothelin A receptor gene targeting, the authors found that compared with control mice, mice lacking endothelin A receptors in renomedullary interstitial cells exhibited reduced BP, enhanced natriuresis and diuresis, increased endogenous natriuretic and diuretic factor production, and reduced medullary transporter expression. These studies identify a role for renomedullary interstitial cells in vivo in regulating renal function under physiologic conditions. Background The physiologic role of renomedullary interstitial cells, which are uniquely and abundantly found in the renal inner medulla, is largely unknown. Endothelin A receptors regulate multiple aspects of renomedullary interstitial cell function in vitro . Methods To assess the effect of targeting renomedullary interstitial cell endothelin A receptors in vivo , we generated a mouse knockout model with inducible disruption of renomedullary interstitial cell endothelin A receptors at 3 months of age. Results BP and renal function were similar between endothelin A receptor knockout and control mice during normal and reduced sodium or water intake. In contrast, on a high-salt diet, compared with control mice, the knockout mice had reduced BP; increased urinary sodium, potassium, water, and endothelin-1 excretion; increased urinary nitrite/nitrate excretion associated with increased noncollecting duct nitric oxide synthase-1 expression; increased PGE 2 excretion associated with increased collecting duct cyclooxygenase-1 expression; and reduced inner medullary epithelial sodium channel expression. Water-loaded endothelin A receptor knockout mice, compared with control mice, had markedly enhanced urine volume and reduced urine osmolality associated with increased urinary endothelin-1 and PGE 2 excretion, increased cyclooxygenase-2 protein expression, and decreased inner medullary aquaporin-2 protein content. No evidence of endothelin-1–induced renomedullary interstitial cell contraction was observed. Conclusions Disruption of renomedullary interstitial cell endothelin A receptors reduces BP and increases salt and water excretion associated with enhanced production of intrinsic renal natriuretic and diuretic factors. These studies indicate that renomedullary interstitial cells can modulate BP and renal function under physiologic conditions.
Impact of immune checkpoint and BRAF inhibitors on the incidence of second primary malignancies (SPM) in melanoma.
Authors: Nibash Budhathoki, Sunita Timilsina, Prashanti Atluri, Jeffrey S. Weber, Marc Justin Braunstein
Journal: Journal of Clinical Oncology (2020)

12061 Background: Prior studies have shown an increased risk of SPM in melanoma, however there is limited data on the incidence of SPM following the 2011 approvals of immune checkpoint (ipilimumab) and BRAF (vemurafenib) inhibitors, which have become standard of care. We present data comparing SPM rates before and after introduction of these agents for advanced cutaneous melanoma. Methods: Adult melanoma patients with regional or distant metastases were identified from SEER-18 database and divided into cohorts: 2005-2010 and 2011-2016. SPM was defined as tumors diagnosed ≥6 months from diagnosis of the primary cancer. SEER*stat was used to calculate SPM by multiple primary standardized incidence ratio based on observed (O) and expected (E) cases. The expected numbers of new cancers of specific types were estimated by assuming that incidence rates for new primary tumors corresponded to sex, age, and calendar time–specific SEER rates for similar invasive primary cancers and applying those rates to the accumulated person-years (PYR) of observation. Excess absolute risk (EAR) of malignancy per 10,000 PYR at risk was calculated as ([O − E]/PYR) × 10,000. Results: As shown in the table, from before 2005-2010, 421 of 7991 patients (5.2%) with advanced melanoma had 444 SPM (O/E ratio 2.2, 95% CI 1.9-2.4, P &lt; 0.0001, EAR 157). In comparison, from 2011-2016, 527 of 9341 patients (5.6%) developed 584 SPM (O/E ratio 2.5, 95% CI 2.3-2.7, P &lt; 0.0001, EAR 193). Incidence of AML, myeloma, and pancreatic cancer increased in 2005-2010, while soft tissue malignancies increased from 2011-2016. The incidence of thyroid, brain, and small bowel tumors increased in both groups from 2005-2016. Conclusions: There is a distinct pattern as well as increased latency of SPM in patients with advanced melanoma in the era of immune checkpoint and BRAF inhibitors. We speculate that reduction in chemotherapy use, augmentation of immunosurveillance, and inhibition of oncogenic pathways may impact the pathogenesis of SPM. [Table: see text]
Clinical features of the fulminant myocarditis
Authors: Jianchang Xie, Lei Lai, Peng Xu, Gangjie Zhu, Lina Sun
Journal: BMJ (2015)

Objective
To review the clinical features of fulminant myocartitis, in order to provide assistance to the clinical management.


Methods
The clinic data of 183 patients with viral myocarditis, including 153 cases of acute myocarditis and 30 cases of fulminant myocarditis admitted in our hospital during January 2008 and Dec 2012 were retrospectively analyzed. The age of onset, interval after virus infect, initial symptoms, auxiliary examination, treatment, and turnover were compared in the study.


Results
The average onset age of fulminant myocartitis and acute myocarditis were similar[(22.3±7.6) vs. (26.2±12.6) years, P=0.105 5]. There was a significant difference between the two gourps in the rate of patients with a explicit history of virus infection[30.0%(9/30) vs. 78.4%(120/153), χ2=28.3, P<0.001], the average interval after virus infect [(3.1±2.2) vs. (7.0±3.80) d, P<0.001] and the length of hospital stay[(12.1±6.9) vs. (6.9±4.50) d, P<0.001].Chest congestion (101/153, 66.0%), feebleness(76/153, 49.7%), fluster(74/153, 48.4%) are the most onset symptoms of acute myocarditis, while chest congestion (24/30, 80.0%), shortness of breath(14/30, 46.7%), feebleness(13/30, 43.3%) in flunimant myocarditis.Advanced A-V block(19/30, 63.3%), cardiogenic shock (18/30, 60.0%), ventricular arrhythmia(16/30, 53.3%), Adams-Stokes syndrome(8/30, 26.67%) and acute renal failure(8/30, 26.7%) were the most complications of flunimant myocarditis.Temporary pacemaker(11 cases), extracorporeal memberane exygenator(7 cases) and intra-aortic balloon pump(7 cases) were applied in critical patients.In acute phase, 21 cases were cured, 9 cases was dead of cardiogenic shock and ventricular(27, 30.0%). Two dead cases applied with ECMO because of delay.After leaving hospital, 1 case was implanted permanent pacemaker, 2 cases became chronic myocarditis and required hospitalization repeatedly.


Conclusions
The fulminant myocarditis has a rapid onset, most of which has no prodrome of virus infection or a shorter interval than acute myocarditis. Timely and effective mechanical circulatory support is critical for fulminant myocarditis.


Key words: 
Myocarditis; Clinical feature; Diagnosis
Low TWEAK expression indicates poor survival and is correlated with sparse TIICs in lung adenocarcinoma (LUAD).
Authors: Jinchun Wu, Xianyu Liu, Yanhua Mou, Shan Zeng, Jin Zhang, RongRong Zhou, Jingchen Lu, Gao Yang, Chunfang Zhang, Chaojun Duan, Bin Li
Journal: Journal of Clinical Oncology (2020)

e21017 Background: Lung adenocarcinoma (LUAD) occupies the most of non-small cell lung cancer (NSCLC) and shows promising response to PD-1 immunotherapy, but immune escape will cause treatment failure indicating poor prognosis. TWEAK (Tumor necrosis factor-related weak inducer of apoptosis, also known as TNFSF12) combining with its receptor FN14 (fibroblast growth factor–inducible 14) mediates crucial innate and adaptive immune pathways to promote the progression of multiple autoimmune diseases. So we assumed that TWEAK is a prognostic predictor and related with tumor-infiltrating immune cells (TIICs) in LUAD. Methods: TWEAK expression of LUAD was primarily investigated in The Cancer Immunome Atlas (TCIA) and then validated in Tumor Immune Estimation Resource (TIMER) databases. We assessed the effect of TWEAK on the survival via the Kaplan-Meier plotter, GEPIA2 (gene expression profiling interactive analysis) and PrognoScan databases. The relation between TWEAK and TIICs was explored in TIMER and TCIA, as well as the correlation of TWEAK and FN14 was analyzed in TIMER and GEPIA2. Results: Low TWEAK expression was significantly associated with poor relapse-free survival (RFS) (HR = 0.62, 95% CI = 0.4~0.97, logrank P = 0.035) and overall survival (OS) (HR = 0.61, 95% CI = 0.46~0.83, logrank P = 0.0012) in LUAD from Kaplan-Meier plotter. Similar impacts of TWEAK on the survival were validated in GEPIA2 and four independent cohorts from PrognoScan (jacob-00182-CANDF, GSE13213, jacob-00182-MSK and GSE31210). Moreover, reduced TWEAK expression was closely related with the paucity of TIICs which contributed to poor OS, including central memory CD8 T cells, plasmacytoid dendritic cells, activated CD8 T cells, monocytes, T follicular helper cells, immature B cells and eosinophils. In addition, TWEAK expression was positively related with the expression level of FN14 in both GEPIA2(R = 0.13, P= 0.0031) and TIMER (partial.cor = 0.212, P= 2.04e-06). Conclusions: Low TWEAK expression maybe indicate poor prognosis in LUAD, and correlated with the impaired infiltration of immune cells in the tumor region. The defective TWEAK/FN14 pathway possibly accounts for these observations, but the underlying mechanism needs to be further explored.