tbuckley/cabot-search huggingface dataset:
Association between inflammatory markers and progression-free survival in patients with advanced EGFR-mutated non-small cell lung cancer under treatment with tirosin kinasa inhibitors: Real-world data from Peru.
Authors: Rodrigo Motta Guerrero, Carlos Aliaga Macha, Carlos F. Carracedo, Thanya Runciman
Journal: Journal of Clinical Oncology (2020)

e21568 Background: Tirosine Kinasa Inhibitors (TKI) are the standard treatment in patients with non-small cell lung cancer (NSCLC) harboring EGFR mutation. However, eventually patients will progress to TKI. The aim of this study is to determinate if neutrophil-lymphocyte ratio (NLR), RDW-CV and platelet-lymphocyte ratio (PLR) are associated with progression free survival (PFS). Methods: This is a retrospective observational study of a single patient cohort. Clinical records of advanced NSCLC patients that received TKI as first line therapy in ALIADA cancer center since January 2015 and December 2019 were evaluated. NLR, RDW-CV and PLR were calculated from blood counts before beginning of TKI. The statistical analysis was performed with SPSS version 20 and MINITAB 14. Results: 182 patients were diagnosed with advanced NSCLC and 30% of them harbor a EGFR mutation. 43 patients were finally included, 55.8% were women and mean age was 58 years. The 65% of patients had exon19 deletion, 25% exon21 L858R substitution, 7% exon20 T790 mutations and 3% exon18 G719X substitution. 44% of patients received erlotinib, 38% afatinib and 18% osimertinib. The 61.5% of patients achieved partial response; they had a mean NLR, PRL and RDW-CV of 2.98 (0.93–7.41), 238.59 (101.63–863.01) and 13.8 (12.6–15.5) respectively. 17.3% achieved complete response, with a mean NLR, PRL and RDW-CV of 2.93 (1.22–4.64), 204.37 (109.21–417.46) and 13.7 (12.8–15.4). Finally, 9.6% maintain stable disease; with a mean NLR, PRL and RDW-CV of 4.25 (3.6-4.91), 200.7 (196.4-205) and 14.35 (14.3-14.4). 74% of patients progressed. The mean PFS was 24.33 months (95% CI 16.05 - 32.6). Patients that developed progressive disease and those who did not, had no significant difference in the mean NLR (3.98 vs 3.68, p = 0.706) and mean RDW-CV (14.12 vs 14.3, p = 0.655). However, patients with clinical benefit during TKI had a mean PLR of 163.68, meanwhile patients with progressive disease had a mean PLR of 276.54 (T of Student, p = 0.03). Conclusions: In patients with advanced EGFR mutated NSCLC, a high level of PLR is associated with a lower PFS. It is necessary to carry out studies with a bigger amount of population to validate the PLR as a predictive biomarker. To our knowledge this is the first study that analyzes these characteristics in Latin American population.
Clinically relevant genomic alterations identified by targeted exome sequencing in U.S. veterans with prostate cancer.
Authors: Eman Dadashian, Michael Nakazawa, Neil Rohit Parikh, Nathisha Kalpage, Nicholas George Nickols, Matthew Rettig
Journal: Journal of Clinical Oncology (2020)

e17599 Background: Amongst male United States Veterans, prostate cancer accounts for one third of cancer diagnoses and is the second leading cause of cancer death. Prostate cancers in the Veteran population may have differing frequencies of clinically relevant genomic alterations than the general population owing to chemical exposures, military service, or other unknown factors. Veterans, however, have been underrepresented in large-scale prostate cancer sequencing cohorts to date. Methods: Archival or fresh prostate cancer tissue from Veterans cared for by our team within the VA Greater Los Angeles Healthcare System (a VA Prostate Cancer Center of Excellence) undergo targeted sequencing as part of routine clinical care through the VA Precision Oncology Program. Sequencing covers over 181 genes frequently mutated in cancers. Prostate cancers from 81 Veterans (76 primary tumors, 5 metastases) have been sequenced through the Personalis ACE CancerPlus platform. Results: 43% of Veterans had primary tumors with clinically relevant genomic alterations, including 6.2% with activating mutations in MAPK pathway members (KRAS, ERBB2, or BRAF), 3.7% with somatic mutations in DDR genes (BRCA2 or ATR), 7.3% with mutations in TP53 or RB1, 4.9% in APC, 1.2% in the WNT pathway (CTNNB1), 3.7% with mutations in the PI3K/AKT pathway (PIK3R1 or AKT1), 3.7% with PTEN deletions, and 22.2% had alterations involving an AR regulated gene (SLC45A3 or TMPRSS). Of the five metastatic tumors sequenced, one had a mutation in TP53 and another had an ETS gene fusion detected. Half of the Veterans who underwent tumor sequencing consented for screening for, or enrollment on, active clinical trials at VA Greater LA. Conclusions: Large-scale sequencing of prostate cancers within VA is feasible and may facilitate enrollment in precision oncology trials specifically designed for Veterans. These data suggest that clinically relevant genomic alterations within the primary tumors may differ between Veterans and the general population; larger data sets along with more robust sequencing platforms are required for clarification.
An Investigation of influence of in-service training on awareness of tuberculosis prevention and detection in health-care workers
Authors: Su-hua Zheng, Hai-ying Li, Ying Ling, Wan-ii Kang
Journal: BMJ (2010)

Objective To investigate awareness about tuberculosis (TB) prevention and treatment and influence of professional training on TB detection among health-care workers (HCWs) in general hospitals.Methods In total,750 HCWs were trained for TB-related knowledge for eight class-hours in a two-day course in three general hospitals,and 20 HCWs from each of the three hospitals classified as grade 3A and grade 2A in urban Beijing and grade B at suburban Beijing,respectively,were interviewed with questionnaire designed to understand their awareness about TB prevention policy,epidemiology,diagnosis and treatment,and to evaluate effectiveness of the training,respectively.All the trainees responded before and after the training,with a hundred percent of response rate.TB diagnosis and reporting one year before training in the three hospitals were compared to those one year after it.Results Scores of knowledge about TB diagnosis and treatment averaged 64-80 for HCWs before training,with statistically significant difference among three hospital (F = 5.984,P ＜ 0.01).Scores increased after training,but without significant difference from those before it (P ＞ 0.05).Awareness of TB prevention policy,regulations and epidemiology was insufficient in most HCWs of those hospitals,with lowest and highest average scores of 38.3 and 71.7 before training,respectively,but scores increased significantly after training (P ＜ 0.01).Proportion of TB diagnosis with chest roentgenograph at grades 3A and 2A hospitals was significantly higher one month,three months and six months after training,as compared to that at suburban hospitals (P ＜0.01).There was significant decrease (P ＜ 0.01) in proportion of chest roentgenograph at respiratory departments in hospitals grade 3A and grade 2A after training.There was no significant difference in reporting of pulmonary TB and positive sputum smear (P ＞ 0.05) before and after training.Conclusions HCWs in general hospitals had experience and capacity in diagnosis and treatment of pulmonary TB,but their knowledge of TB prevention policy and epidemiology was insufficient.Their ability in finding and reporting TB can not been improved with short-term training.

Key words: 
Tuberculosis,pulmonary;  Questionnaires;  Inservice training
A phase III randomized, double-blind placebo controlled study of armodafinil (Nuvigil) to reduce cancer-related fatigue in patients with high-grade glioma (Alliance A221101).
Authors: Alyx B. Porter, Heshan Liu, Sadhna Kohli, Jane H. Cerhan, Jeff A. Sloan, Ryan McMurray, Jennifer Le-Rademacher, Charles L. Loprinzi, John L. Villano, Sani Haider Kizilbash, Minesh P. Mehta, Kurt A. Jaeckle, Paul D. Brown
Journal: Journal of Clinical Oncology (2020)

12007 Background: Up to 96% of patients with high grade glioma (HGG) report moderate to severe fatigue. Armodafinil, the R-enantiomer of modafinil, is a psychostimulant with low potential for abuse that has shown potential for improving severe fatigue in HGG patients. Methods: In this phase III double blinded placebo-controlled study, adults with HGG and moderate to severe fatigue, &gt; 4 weeks after completing radiotherapy, were randomized to receive armodafinil daily (150 mg or 250 mg) or placebo for a total of 8 weeks. The primary outcome was efficacy in treating severe fatigue. Secondary outcomes included evaluation of tolerability, neurocognitive function, and quality of life. Patients were evaluated at baseline, 4 and 8 weeks. Results: A total of 328 patients were enrolled between 6/3/13-3/1/19. There were 103 (150 mg arm), 97 (250 mg arm) and 97 (placebo arm) evaluable patients with primary endpoint data available. The median age was 60 years (20-85) with a median Brief Fatigue Inventory (BFI) worst fatigue score of 8 (6-10). 60.3% were male, 80.5% received concomitant chemotherapy, and 39.7% were on corticosteroids. The global fatigue score at end of weeks 4 and 8 were lower than at baseline (p&lt;0.0001) and in the 250 mg arm than placebo (p=0.0356) and was higher for corticosteroid users than non-users (p=0.0002). There was no statistically significant difference for clinically meaningful improvement in BFI usual fatigue score from baseline to end of week 8 between the three arms (p=0.9601). Patients reported an improvement in concentration at week 4 from baseline on the 150 mg arm(P=0.0311). There was no statistically significant difference on neurocognitive tests from baseline to end of week 4 (p&gt;0.05) or week 8 (p&gt;0.05) between arms. More patients reported insomnia on the 250 mg arm (p=0.0083). Conclusions: There is no meaningful benefit of the use of armodafinil to reduce moderate to severe fatigue in patients with HGG. In certain cases there may be benefit of armodafinil 150 mg to aid concentration without the risk of insomnia.Support: UG1CA189823;U10CA180868 (NRG). Clinical trial information: NCT01781468 .
Effects of high-frequency oscillatory ventilation plus sildenafil in severe persistent pulmonary hypertension of newborns
Authors: Yu-xiang Zhao, Liang-rong Han, Rong Wu, Dong-lin Ji
Journal: BMJ (2013)

A total of 60 infants with severe persistent pulmonary hypertension (PPHN) at our NICU from January 2006 to December 2012 were divided into research group[(n=32, high-frequency oscillatory ventilation (HFOV) plus sildenafil)]and control group (n=28, HFOV only). Mean pulmonary arterial pulmonary arterial (MPAP), blood gas analysis, oxygenation index (OI), PO2 to fraction of inspired oxygen ratio (PO2/FiO2) before and after treatment were compared between two groups. After 3-day treatment, MPAP (mm Hg)(32±6) vs. (43±9) mm Hg, PCO2 (mm Hg)(36±9) vs. (43±9), OI (56±22) vs.(85±21) in research group were significantly lower than those in control group (P<0.05); in comparison with control group, PO2 (mm Hg)(89±15) vs. (72±22), PO2/ FiO2 (mm Hg)(223±18) vs. (196±24) in research group were significantly higher (P<0.05). The time of ventilation use (d)(5.4±1.3) vs. (6.3±1.6) in research group was shorter than that of control group (P<0.05) while research group showed a higher clinical efficiency rate (%)(81.2 vs. 50.0)(P<0.05). A combination of HFOV and sildenafil for severe PPHN can significantly reduce MPAP, shorten the duration of ventilation use and improve cure rate.


Key words: 
Hypertension, pulmonary; High-frequency ventilation
Underwater peroral endoscopic myotomy
Authors: Rachel Hallit, Maximilien Barret, Einas Abouali, Arthur Belle, Chloé Leandi, Romain Coriat, Stanislas Chaussade
Journal: Endoscopy (2020)

Peroral endoscopic myotomy (POEM) is an accepted treatment modality for achalasia [1]. However, postoperative pain, mainly related to CO2 insufflation causing pneumothorax, pneumomediastinum, and pneumoperitoneum, occurs in 25 % – 85 % of patients [2] [3]. Underwater endoscopic resection is an emerging strategy for the management of duodenal and colorectal lesions [4]. We introduced underwater POEM with the aim of limiting the complications of CO2 insufflation.
Predictive value of bother by side effects of treatment prior to protocol therapy for early treatment discontinuation in clinical trials.
Authors: Fengmin Zhao, John Peipert, Ju-Whei Lee, Fangxin Hong, Edward Ip, Ilana F Gareen, Nathaniel O'Connell, Ruth Carlos, Ingrid A. Mayer, Kathy Miller, Ann H. Partridge, Tait D. Shanafelt, A. Keith Stewart, Ahmad A. Tarhini, Mary L Thomas, Matthias Weiss, Joseph A. Sparano, David Cella, Robert James Gray, Lynne I. Wagner
Journal: Journal of Clinical Oncology (2020)

e19132 Background: The Functional Assessment of Cancer Therapy–General has an item about patient tolerability of treatment: “I am bothered by side effects of treatment” (GP5). We examined the predictive value of this single item for early treatment discontinuation in clinical trials. Methods: GP5 level prior to protocol therapy (rated using a 5-point Likert scale) and treatment start/end dates and off treatment reason data at each treatment phase were drawn from five phase III clinical trials conducted by ECOG-ACRIN. In the present analysis, GP5 was dichotomized as 0 = “Not at all”/“A little bit” and 1 = “Somewhat”/“Quite a bit”/“Very Much”. Early treatment discontinuation was defined either as receiving less than protocol specified cycles of treatment when maximum cycles specified in the protocol (E1A06 induction, E1912 induction, E1609 induction, E1105 induction, E5103 adjuvant), analyzed using logistic regression via odds ratio [OR]), or treatment cessation for reasons other than progressive disease or death when treatment continued until progression or intolerability (E1A06 maintenance, E1912 maintenance, E1609 maintenance, E1105 maintenance), analyzed using Cox proportional hazard model via hazard ratio [HR]. Results: GP5 prior to treatment was significantly associated with early discontinuation of E1A06 maintenance, E1609 maintenance, E1912 maintenance, and E1912 induction. No significant association was found for other therapies examined in the study. Conclusions: High GP5 level prior to treatment is associated with higher likelihood of early treatment discontinuation in patients who have received previous treatment. The limited predictive value of GP5 for treatment naïve patients is more limited, serial on-treatment assessment should be considered in this setting. Clinical trial information: NCT00602641 . [Table: see text]
Different efficacy of osimertinib in pre-TKI treated NSCLC patients with brain metastases harboring EGFR exon 19del and L858R mutant.
Authors: Xuanzong Li, Ruozheng Wang, Bing Zou, Dai Zhang, Jinming Yu, Linlin Wang
Journal: Journal of Clinical Oncology (2020)

e21667 Background: Previous studies suggested that the efficacy of osimertinib was better in patients with epidermal growth factor receptor ( EGFR) exon 19 deletion (ex19del) than exon 21 Leu858Arg (L858R). However, the differential clinical outcomes of osimertinib in previous tyrosine kinase inhibitors (TKIs) treated non-small-cell lung cancer (NSCLC) patients with brain metastases (BrMs) according to the two different common EGFR genotypes remains undetermined. Methods: We retrospectively collected EGFR mutant (ex19del and L858R) NSCLC patients with BrMs and received osimertinib treatment between Jan 2016 and Feb 2019 in our hospital. Other eligible standards including Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2, osimertinib 80mg monotherapy and neurologic symptoms existing was permitted to enroll in our study. Results: 78 patients with EGFR mutant NSCLC and BrMs were included in the study. EGFR mutation types were ex19del in 55% of patients (43/78) and L858R in 45% of patients (35/78). All of patients received at least one prior EGFR-TKI therapy, among which 46% (36/78) had gefitinib, 49% (38/78) had erlotinib, 19% (15/78) had icotinib. T790M status at osimertinib initiation was positive in 81% of patients (63/78), negative in 4% (3/78), unknown in 15% (12/78). The systemic objective response rate (ORR) was 46%. There was no apparent difference in systemic ORR (49% vs 43%, P = 0.598) between ex19del group and L858R group. The median progression free survival (PFS) and overall survival (OS) were 7.0 (range 4.7-9.3) and 18.8 (range 14.0-23.5) months for all patients. The median PFS in the ex19del and L858R subgroups was 9.1 (range 6.0-12.1) months and 5.3 (range 3.4-7.2) months, respectively ( P = 0.031). The median OS in the ex19del and L858R subgroups was 26.0 (range 13.7-38.3) months and 13.9 (range 7.7-20.2) months, respectively ( P = 0.033). Multivariate analysis identified L858R and ECOG PS 2 as poor independent predictors to the PFS and OS. Conclusions: The efficacy of osimertinib was associated with EGFR genotypes in pre-TKI treated NSCLC patients with BrMs, and L858R maybe an independent bad factor for long-term outcomes of osimertinib.
Racial differences in development of immune-related adverse events.
Authors: Shruti Bhandari, Rohit Kumar, Laura Nice, Anmol Cheema, Goetz H. Kloecker
Journal: Journal of Clinical Oncology (2020)

e15148 Background: Immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICIs) are caused by non-specific immune system activation and develop in 30-70% of patients. The goal of this study is to examine the association of race with the development of irAEs secondary to ICIs as autoimmune diseases generally exhibit racial differences. Methods: A retrospective chart review was done using University of Louisville pharmacy database. Patients with solid cancers who received ICIs between Jan 2016 to June 2019 were included. IrAEs were identified through the review of electronic medical records. Descriptive analysis evaluated the incidence and severity of irAEs. Multivariable logistic regression was used to calculate standardized incidence of irAEs among Whites and African Americans. Results: A total of 476 patients were included in this study. The mean age was 61 years, 57% were males and 89.7% were whites. A majority of patients had melanoma (50%). The remainder of the dataset included lung (33.4%), gastrointestinal (7.4%), head &amp; neck (4.8%), breast (2.5%) and genitourinary (1.9%) cancers. ICIs included single agent anti-PD-1 (74.8%), single agent anti-PD-L1 (9.4%), combination anti-CTLA-4 with anti-PD-1 (7.1%). Some patients were also treated with &gt; 1 ICI as subsequent therapy (8.6%). Overall, the rate of irAEs was 44.3% with 33.8% grade 1-2 and 12.4% grade 3-4 irAEs. There was no difference in development of any grade irAEs in Whites as compared to African Americans after adjusting for age, sex, cancer type and ICIs (44.3% vs 44.2%; OR: 0.99, 95% CI: 0.50 – 1.97; p = 0.99). There was also no difference in development of grade 3-4 irAEs in whites as compared to African Americans (12.8% vs 14.5%; OR: 1.16, 95% CI: 0.43 – 3.12; p = 0.75). Conclusions: In this study, we found no racial difference in the development of irAEs between Whites and African Americans. This is in contrast to general autoimmune diseases which exhibit racial differences with higher prevalence among African Americans compared to Whites. We will continue to accrue patients to this study as larger sample size is needed to confirm these findings.
Screening of anti-M2 mitochondrial antibody in elderly population
Authors: Bihua Chen, Xuling Wu, Caijuan Su
Journal: BMJ (2014)

Serum anti-M2 mitochondrial antibody (AMA-M2) was screened with immune colloidal gold technique in 6 008 individuals aged over 60 years who underwent health check-up in Xuhui District of Shanghai, the positive samples were retested with ELISA method. The results showed that 1.31%(79/6 008) individuals were AMA-M2 positive; the positive rate was 0.82% (18/2 186) in males and 1.60% (61/3 822) in females. Eleven subjects with positive AMA-M2 underwent further investigation, 8 cases were diagnosed as primary biliary cirrhosis (PBC) and the remaining 3 were highly suspected as PBC. All 11 individuals were abnormal in biochemical tests of liver function and/or clinical symptoms.


Key words: 
Liver cirrhosis, biliary; Mass screening
Roles of neurovascular unit in cognitive impairment induced by chronic cerebral hypoperfusion
Authors: Dapeng Wang, Yifang Wu
Journal: BMJ (2017)

Chronic cerebral hypoperfusion (CCH) may result in neurovascular unit (NVU) injury, causing cognitive impairment. The NVU consists of neurons, glial cells, vascular cells and extracellular matrix. The damage of NVU can induce the blood-brain barrier dysfunction, abnormal cell signaling, as well as cognitive impairment. However, its molecular mechanism is unclear. Thus, investigating the role of NUV in CCH-induced cognitive impairment may provide a theoretical basis for the novel treatment of cognitive impairment.


Key words: 
Brain ischemia; Cognitive disorders; Neurovascular unit
Detailed disease management model in community management of hyperuricemic patients
Authors: Qi Wang, Feng Zhou
Journal: BMJ (2015)

Objective
To evaluate the effect of detailed disease management model in community management of hyperuricemic patients.


Methods
One hundred and fifty patients with primary hyperuricemia were randomly divided into detailed management group and conventional group from April to June 2012, patients in two groups were managed by different models for 1 year.The weight, height, biochemical indexes including blood uric acid and serum lipids were measured and a questionnaire survey was conducted with the items of disease awareness score, smoking, drinking, diet, standard treatment, satisfaction of treatment etc. before and after management.


Results
One hundred and thirty six patients completed the study including 68 in detailed management group and 68 in conventional group.After one year management, the blood uric acid, triglyceride, low density lipoprotein (all P 0.05). The disease awareness score increased from (65.4±5.4) to (82.7±4.2)(Z=-10.2, P<0.01), high purine diet rate fell from 47.1% to 7.4% (χ2=33.6, P<0.01), the standard treatment rates increased from 10.3% to 85.3% (χ2=76.6, P<0.01), treatment satisfaction rate increased from 51.5% to 88.2% (χ2=21.8, P<0.01) in detailed management group.In detailed management group, the blood uric acid (Z=-7.4, P<0.01), total cholesterol (Z=-0.01, P<0.01), triglyceride (Z=-2.4, P<0.01) and low density lipoprotein (Z=-3.2, P=0.03) and high purine diet rate were lower (χ2=27.1, P<0.01), the standard treatment rate (χ2=70.6, P<0.01) and treatment satisfaction rate were higher (χ2=5.6, P=0.02) than those in conventional group after 1 year management.


Conclusion
Detailed disease management is an applicable and effective model for community management of hyperuricemic patients.


Key words: 
Hyperuricemia; Disease management; Community health services
How Chinese psychiatrists see and manage stigmatisation of psychiatric patients: a qualitative study in Hong Kong
Authors: Sun Kai Sing, Lam Tai Pong, Lo Tak Lam, Wu Dan, 崔轶
Journal: BMJ (2019)

背景
据报道，包括精神科医生在内的卫生专业人士对精神病患者存在偏见。他们的观点可能受到临床、社会和文化因素的影响。


目的
本研究探讨了中国精神科医生对精神病患者污名化的看法。


方法
在中国香港进行了与精神科医生的焦点小组讨论。讨论了他们对精神病患者污名化的看法和减少污名化的策略。


结果
精神科医生认为，临床上需要根据诊断对患者进行分类，他们不认为这是一种污名化。他们认为某些精神疾病的特征是暴力或异常行为，并且无法完全治愈。他们没有试图消除污名化，而是在处理方式上考虑到了社会期望。医生可能会给出一个相对模糊的诊断标签，以挽回患者的面子，并确保公众对这种疾病的接受程度更高。他们倾向于同意家庭成员代表患者做决定。为了调和公众利益和患者的自主权，他们鼓励稳定的精神病患者住在社区里，但同意将那些有暴力行为的患者管理起来。


结论
虽然精神科医生们认为，诊断结果并不是污名的一种形式，但他们仍十分注意以最不污名化的方式回应患者。他们倾向于认为，鉴于某些精神疾病的性质，污名是不可避免的。在中国的大环境下，掩盖污名似乎是处理污名的常用方法。


临床意义
精神科医生，特别是在中国执业的精神科医生，可以从更广阔的视角来考虑社区精神健康康复，不仅限于社会稳定，还包括社会生活。