tbuckley/cabot-search huggingface dataset:
Serum NK cells levels in HBeAg positive early pregnant women with immune activation
Authors: Hongfang Ju, Hongtao Xu, Meilong Shen, Shimin Xu
Journal: BMJ (2015)

Objective
To investigate serum NK cell levels in HBeAg positive early pregnancy women with immune activation.


Methods
Fifty four HBeAg positive pregnant women admitted in Taizhou People′s Hospital from September 2010 to April 2013 were enrolled in the study. Among them, the serum HBV DNA load decreased ≥2 log at 12 weeks after pregnancy in 24 cases (immune activation group) and HBV DNA did not decrease in 30 cases (immune tolerance group). The serum level of alanine aminotransferase (ALT), total bilirubin, HBeAg, HBV DNA load and NK cells were measured.


Results
At week 12 of gestation, the mean ALT levels and ALT abnormality rate in immune active group were higher than those in immune tolerance group [(146.7±93.1) vs. (44.1±14.7) U/L, t=2.95, P<0.05, 50.0% vs. 6.7%, χ2=4.97, P<0.05]. There was no significant difference of HBeAg level between two groups before pregnancy, while HBeAg level in immune activation group was lower than that in immune tolerance group at week 12 week of gestation [(291.8±170.5) vs. (443.7±289.9)S/CO, t=2.81, P<0.05]. The percentage and absolute number of NK cells in immune activation group were higher than those in immune tolerance group [(26.7±9.1)% vs. (17.1±7.8)%, t=2.52, P<0.05 and (370.9±136.4)/μl vs. (213.2±97.8)/μl, t=2.38, P<0.05, respectively].


Conclusions
In HBeAg positive early pregnant women with immune activation, the inhibition of HBV DNA might be associated with the activation of NK cells.


Key words: 
Pregnancy trimester, first; Hapatitis B e antigens; Hepatitis B virus; HBV DNA; Natural killer cells
Application of mini-CEX in community rotation of general practice residency training
Authors: Jie Gu, Yao Shen, Yuting Jiang, Zhigang Pan, Shanzhu Zhu
Journal: BMJ (2015)

Objective
To evaluate the effectiveness of mini clinical evaluation exercise(mini-CEX) in community rotation of general practice residency training.


Methods
Forty nine general practice residency trainees, who participated in community rotation during July 2012 to July 2014 in 3 community teaching bases, were randomly divided into two groups: 25 trainees in intervention group received conventional teaching and additional 2 rounds of mini-CEX in one month, and 24 trainees received conventional teaching only. The changes of self-evaluation scores of clinical competence after the community rotation were evaluated. Focus group discussions of 8 trainees and 8 teachers from intervention group were also adopted in January to February 2013 to assess the effectiveness of mini-CEX.


Results
Three trainees withdrew in the study and the interventional group completed 232 mini-CEXs. The self-evaluation scores of clinical competence were elevated in all items in interventional group after community rotation(from 7.03±0.68 to 7.30±0.77 in medical history, from 7.00±0.83 to 7.18±0.88 in physical examination, from 7.42±1.20 to 7.52±0.76 in humanistic qualities, from 6.79±0.82 to 7.12±0.70 in clinical judgment, from 6.85±1.06 to 7.18±0.81 in counseling skills, from 6.85±1.15 to 7.12±0.96 in organization, from 7.09±0.81 to 7.33±0.69 in overall competence), while in control group, scores of humanistic qualities(from 7.74±0.89 to 7.60±0.97), clinical judgment(from 6.94±0.77 to 6.77±1.10) and organization/efficiency(from 6.94±0.96 to 6.80±0.76) were declined. After adjusting self-evaluation score before rotation, the increased scores in clinical judgment(7.12±0.70 vs. 6.77±1.10, F=4.339, P=0.042)and organization(7.12±0.96 vs. 6.80±0.76, F=4.336, P=0.042)of intervention group were significantly higher than those of control group. In focus group discussions both trainees and teachers recognized that mini-CEX would enhance clinical competence, be more comprehensive in assessing and adaptable in training program than former rotation tests. The major concerns of using mini-CEX were subjective rating process, non-unified rating standards and insufficient teaching ability.


Conclusions
Application of mini-CEX in community rotation of general practice residency training can enhance clinical competency of trainees.


Key words: 
General practioners; Teaching; Mini clinical evaluation exercise
Alzheimer disease and general practitioners
Authors: 张明园
Journal: BMJ (2006)

阿尔茨海默病(Alzheimer disease,AD)是一类以大脑神经元淀粉样变性和神经原纤维缠结为病理特征的神经变性疾病,临床上以痴呆为主要表现.Alzheimer于1907年报告的是一名51岁的痴呆患者,因而有人将之纳入早老性痴呆.以后的研究发现,所谓老年性痴呆(senile dementia)也呈现同样的病理变化.国际疾病分类第10版(ICD-10)将65岁以前发病者称为AD,早发型;65岁以后发病者为AD,晚发型.90%以上的AD为晚发型.如果没有特殊说明,一般文献中的AD指的都是晚发型。
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) associated to systemic chemotherapy for gastric cancer with diffuse peritoneal metastases in a palliative setting.
Authors: Pierre Emmanuel Bonnot, Thomas Rabel, Alexandru Lintis, Nathalie Laplace, Naoual Bakrin, Vahan Kepenekian, Laurent Villeneuve, Marion Chauvenet, Nadia Bouarioua, Mohammad Alyami, Olivier Glehen
Journal: Journal of Clinical Oncology (2020)

e16538 Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is emerging as a new intraperitoneal laparoscopic delivery of chemotherapy to treat peritoneal metastasis (PM). First results from several malignancies appear promising in small series of patients. Prognosis of PM from gastric cancer (GC) is poor. Median survival is ranging from 3 to 13 months with systemic chemotherapy (SC) alone. Purpose: to evaluate the feasibility and potential benefits of PIPAC associated to SC in GC with PM in a palliative setting Methods: From a prospective database, we identified 91 consecutive patients considered with isolated unresectable PM from GC treated by an alternance of SC and PIPAC with low-dose cisplatin-doxorubicin (ratio 2/1) between January 2016 and January 2019 in our institution. End of follow-up was January 2020. Results: Median age was 56 years, 86% of patients had a signet ring cell adenocarcinoma with 86.7% of synchronous PMs.Median Peritoneal Cancer Index was 16 (3-39). A total of 346 PIPAC were performed with a median of 3 per patient (1-18). Median number of SC lines was 3 (2-3) resulting in a median number of SC cycles of 14 (11-20). After a median follow-up of X months, 21 patients were still alive. In the whole population, median OS from diagnosis was 15.1 months. PIPAC was introduced in association to first-line SC as maintenance or intensification therapy in 75 patients with a median survival from diagnosis of 14.7 months and a median PFS from PIPAC introduction of 6.3 months. For 16 patients, PIPAC was introduced due to progression after a first or second line of SC leading to a median OS of 20 months after diagnosis and 5.9 months after PIPAC introduction. Reasons to stop PIPAC were cancer progression, intraperitoneal access difficulties or PIPAC related morbidity, a cytoreductive surgery attempt in 61.7%, 19.8% and 18.5% respectively. A cytoreduction and HIPEC attempt was performed for 12 patients before 3 PIPAC and 3 after 3 PIPAC or more, leading to a median OS of 19 months for those patients. Twelve (13,2%) patients developed extra-peritoneal metastases during PIPAC. Conclusions: PIPAC appears safe and feasible showing promising results in control of PMs from gastric origin. Further randomized studies are required to document its benefits compared to SC alone.
Progress in embolic stroke of undetermined source
Authors: Wei Huang
Journal: BMJ (2016)

Embolic stroke of undetermined source (ESUS) refers to non-lacunar brain infarcts without definite proximal arterialstenosis or major cardioembolic sources. Paroxysmal atrial fibrillation may be the most important cause of ESUS, thus anticoagulation may be more effective than antiplatelet therapy for secondary stroke prevention to this group of patients. This paper reviews the latest progress on the definition, epidemiology, diagnostic approach, relation to atrial fibrillation and management of ESUS.


Key words: 
Brain infarction, unknown origin; Atrial fibrillation; Anticoagulation
是急性胃肠炎吗
Authors: 黄文娟, 周仲华
Journal: BMJ (2009)

1个月前,我在肠道门诊接诊了一个因疑似急性胃肠炎被分诊来的老年病人. 这个女病人78岁,从陕西来海南旅游,主诉是腹痛、腹泻、呕吐2小时.2小时前在机场候机时自觉中上腹持续绞痛,程度较轻,伴腹泻黄色稀便2次,量少,无黏液脓血,无里急后重;恶心,呕吐胃内容物2次,量少,无呕血.病人无头晕、头痛,无发热、咳嗽、咳痰,无胸闷、胸痛、呼吸困难,无尿频、尿急、尿痛等.休息后仍有中上腹痛,偶有背心放射痛,出汗明显。
Percutaneous transthoracic biopsy in pathologic diagnosis of stage I～II lung cancer
Authors: Zhen-shun Cheng, Jiong Yang, Yu-hui Lin, Yan-qing Ye, Shi-qing Zou, Yi-bin Yang, Wei-ming Liu, Bing Liu
Journal: BMJ (2009)

Fifty-six patients diagnosed as early stage lung cancer by spiral CT scan,underwent CTguided percutaneous transthoracic biopsy with a successful rate of 100%.Forty nice cases were confirmed pathologically including adenocarcinoma in 30 cases,squamous carcinoma in 14,alveolar cell carcinoma in 2 and small cell lung cancer in 3.Three cases were diagnosed as chronic inflammatory lesion,2 cases as tuberculosis and the diagnosis was not confirmed in 2 cases.The results suggest that CT-guided percutaneous transthoracic biopsy is an effective diagnostic measure for patients with stage Ⅰ-Ⅱ lung cancer.

Key words: 
Punctures; Lung neoplasms
Evaluation of the incidence of acute nausea and vomiting after administration of an amino acid solution containing only arginine and lysine with lutetium Lu-177 dotatate.
Authors: Nicholas Alonzo, Magdalena Seyer, Eun-Jeong Kim, Rawmina Keshavarzi, Kathryn Yee, Pamela L. Kunz
Journal: Journal of Clinical Oncology (2020)

12113 Background: Lutetium Lu-177 dotatate is used to treat patients with gastroenteropancreatic neuroendocrine tumors, and an amino acid (AA) solution must be administered concurrently to mitigate nephrotoxicity. AA solutions may lead to increased rates of nausea and vomiting (NV) due to the inclusion of unnecessary non-essential and essential AA. Methods: This study is a single academic center retrospective chart review from October 6 th , 2015 to December 17 th , 2019 evaluating the incidence of acute NV in adult patients after administration of an AA solution containing only arginine 25 grams and lysine 25 grams in 1 liter of normal saline (Arginine-Lysine amino acid [AL AA]) with lutetium Lu-177 dotatate. The incidence of acute NV will be compared to the historical incidence in patients administered Parenteral amino acids 10%, Aminosyn II 10% or Clinisol 15% (commercial AA). Secondary endpoints include the incidence of rescue anti-emetic usage and the percentage of patients that require interruption of the AA infusion. Acute NV are defined as any occurrence of NV within twenty-four hours of the AA infusion. Results: 53 patients received a total of 164 treatments with the AL AA, while 18 patients received a total of 48 treatments with the commercial AA. The AL AA significantly decreased the incidence of acute NV, the mean AA infusion time, the interruption of the AA infusion, and the utilization of rescue anti-emetics compared to the commercial AA (Table) in patients on lutetium Lu-177 dotatate. Conclusions: The study findings support the use of an AL AA to be administered concurrently with lutetium Lu-177 dotatate to minimize commercial AA related acute NV. [Table: see text]
PD-L1 IHC 22C3 pharmdx demonstrates precision and reproducibility in detecting PD-L1 expression in triple negative breast cancer.
Authors: Karina Kulangara, Brittany Watts, Monika Vilardo, Christopher La Placa, Judith Frederick, Siena Tabuena-Frolli, Malinka Jansson, Kristopher Kersch
Journal: Journal of Clinical Oncology (2020)

e13104 Background: PD-L1 IHC 22C3 pharmDx is an FDA-approved, companion diagnostic assay intended for use in the detection of PD-L1 protein in formalin-fixed paraffin-embedded (FFPE) non-small cell lung cancer (NSCLC), gastric or gastroesophageal junction (GEJ) adenocarcinoma, esophageal squamous cell carcinoma (ESCC), cervical cancer, urothelial carcinoma, and head and neck squamous cell carcinoma (HNSCC) tissues. Methods: Additionally, device precision (inter- and intra-observer, inter-instrument, inter-operator, inter-day, inter-lot, and intra-run) and robustness have been validated at Dako North America for triple negative breast cancer (TNBC) using the Combined Positive Score (CPS) ≥1 cutoff. Device precision (excluding inter- and intra-observer) has also been validated for TNBC using the CPS ≥10 cutoff. External validation studies for TNBC (inter- and intra-site, inter- and intra-observer) were conducted at three CAP-accredited and/or CLIA-licensed laboratories using the CPS ≥1 and CPS ≥10 cutoffs. Results: The precision, robustness, and external validation studies achieved point estimates greater than 85% for positive, negative, and overall percent agreement. Conclusions: Internal and external validation studies demonstrate that PD-L1 IHC 22C3 pharmDx is sensitive, specific, precise, robust, and reproducible in evaluating PD-L1 expression at CPS ≥1 and CPS ≥10 cutoffs using TNBC tissue.
Pyrotinib plus capecitabine for HER2-positive, trastuzumab-resistant metastatic breast cancer: A pooled analysis of three randomized controlled trials.
Authors: Zefei Jiang, Binghe Xu, Min Yan, Quchang Ouyang, Xi-Chun Hu, Wei Li, Ji Feng Feng, Qingyuan Zhang, Zhongsheng Tong, Ping Yan, Xiaoyu Zhu, Shangyi Rong, Jianjun Zou
Journal: Journal of Clinical Oncology (2020)

1048 Background: Trastuzumab is the most widely used anti-HER2 agent in patients (pts) with HER2-positive breast cancer, both in (neo)adjuvant and metastatic settings; however, drug resistance is inevitable. This pooled study aimed to investigate the efficacy of pyrotinib plus capecitabine in pts with HER2-positive, trastuzumab-resistant relapsed or metastatic breast cancer. Methods: Data were derived from three randomized controlled trials, including a phase II (NCT02422199) and the PHOEBE phase III (NCT03080805) study comparing pyrotinib plus capecitabine vs lapatinib plus capecitabine and the PHENIX phase III (NCT02973737) study comparing pyrotinib plus capecitabine vs placebo plus capecitabine. Pts with trastuzumab-resistant disease were included in the analyses, including 39 pts who had relapsed within six months after adjuvant trastuzumab and 57 pts who had progressed within three months of trastuzumab treatment for metastatic disease. The pooled tumor response data (per blinded independent central review) were reported herein. Results: In the pooled analysis of all three studies, 63 pts received pyrotinib plus capecitabine. Among them, 28 (44.4%) pts had disease progression or died. The median progression free survival (PFS) was 12.4 months (95% CI, 6.9 to not reached). In total, 40 pts (63.5% [95% CI, 50.4% to 75.3%]) achieved objective response, and the estimated median duration of response (DoR) was 11.1 months (95% CI, 6.9 to not reached). In the pooled analysis involving the phase II and PHOEBE phase III, 43 pts were treated with pyrotinib plus capecitabine and 33 pts with lapatinib plus capecitabine. In total, 18 (41.9%) pts with pyrotinib plus capecitabine and 17 (51.5%) pts with lapatinib plus capecitabine had disease progression or died. The PFS tended to be prolonged with pyrotinib plus capecitabine vs lapatinib plus capecitabine (median, 12.4 months [95% CI, 6.9 to not reached] vs 6.9 months [95% CI, 5.5 to not reached]; hazard ratio, 0.62 [95% CI, 0.31 to 1.24]; p=0.0864). The objective response rate was 67.4% (95% CI, 51.5% to 80.9%) with pyrotinib plus capecitabine compared with 54.5% (95% CI, 36.4% to 71.9%) with lapatinib plus capecitabine. The estimated median DoR was 11.1 months [95% CI, 6.9 to not reached] vs not reached [95% CI, 4.2 months to not reached], respectively. Conclusions: Pyrotinib plus capecitabine showed favorable efficacy in pts with HER2-positive, trastuzumab-resistant relapsed or metastatic breast cancer. This combination could be a treatment option for this population.
MDNA55 survival in recurrent glioblastoma (rGBM) patients expressing the interleukin-4 receptor (IL4R) as compared to a matched synthetic control.
Authors: John H. Sampson, Achal Achrol, Manish K. Aghi, Krystof Bankiewicz, Martin Bexon, Steven Brem, Andrew Jacob Brenner, Chandtip Chandhasin, Sajeel A. Chowdhary, Melissa Coello, Sunit Das, Seunggu Jude Han, Santosh Kesari, Fahar Merchant, Nina Merchant, Dina Randazzo, Michael A. Vogelbaum, Frank Vrionis, Miroslaw Zabek, Nicholas A. Butowski
Journal: Journal of Clinical Oncology (2020)

2513 Background: MDNA55 is an engineered IL-4 fused to pseudomonas exotoxin A being developed for GBM, an aggressive, universally fatal disease. No curative therapy exists and 75% of patients are not eligible for resection at recurrence. MDNA55 targets IL4R overexpressed in GBM, the immunosuppressive tumor microenvironment, and high expression is associated with poor survival outcomes in GBM. A Ph 2b trial of MDNA55 was completed in rGBM using convection-enhanced delivery to bypass the BBB. Here we report results from the Ph 2b trial and comparison against a matched Synthetic Control Arm (SCA). Methods: MDNA55-05 is an open-label, single-arm study of intratumoral delivery of ≤ 240 μg MDNA55 as a single treatment via ≤ 4 catheters in de novo GBM without IDH1/2 mutation at 1st or 2nd recurrence not eligible for resection, tumors ≤ 4 cm, KPS ≥ 70. IL4R expression in GBM tissues was determined by H-Score using a validated IHC assay. 1 o endpoint is median overall survival (mOS); 2 o endpoint includes the impact of IL4R status on mOS. An eligibility-matched SCA was identified retrospectively from patient registries at major neurosurgery centers with access to GBM tumor tissue banks under IRB-approved protocols. Results: 44 subjects comprise the MDNA55 per protocol analysis population: median age 56 (35 - 77); median dose 177 mg (range 18 – 240 mg), 50% had KPS ≤ 80. No systemic toxicities observed, drug-related AEs were primarily neurological and characteristic of GBM, no deaths attributed to MDNA55. Median OS was 11.6 months (95% CI 7.9 – 15.2). When stratified by IL4R expression, mOS in IL4R High (n = 21) was 15 vs. 8.4 months in IL4R Low (n = 19); p = 0.2175. OS12 is 57% vs. 33%. When compared to the SCA (n = 81), MDNA55 subjects survived significantly longer: mOS 12.4 vs. 7.7 months; p = 0.0077. When comparing IL4R High groups, mOS in MDNA55 (n = 21) was 15.8 vs. 6.2 months in the SCA (n = 17); p = 0.0626. Subgroup analysis in unmethylated MGMT subjects also show better survival with MDNA55 (n = 23) than the SCA (n = 31); mOS 12.3 vs. 7.7 months (p = 0.0268), indicating that MDNA55 may be beneficial in patients resistant to temozolomide. Conclusions: MDNA55 subjects represent a difficult to treat population ( de novo GBM, IDH wild-type, not eligible for surgery at recurrence). Single treatment with MDNA55 prolongs survival by nearly 10 months in a subset of rGBM expressing high levels of IL4R when compared to a matched SCA, providing an unprecedented outcome for this highly lethal disease. Clinical trial information: NCT02858895 .
Expression profile and co-expression analysis of ADH1A in human solid tumors.
Authors: Wenqi Huang, Mi Yang, Xixi Wu, Lu Yuan, Yuting Wu, Jihong Hwang, Jian Guan, Laiyu Liu
Journal: Journal of Clinical Oncology (2020)

e13533 Background: The human alcohol dehydrogenase (ADH) gene family is associated with various solid cancers. It seems that the ADH1 gene cluster plays an important role in various solid tumors, so it aroused our interest in studying these genes to find out their functions and biological process within different solid tumors. Methods: Paired tumor and normal tissues gathered from 38 tumor patients, and 5 male BALB/c mice tissues were collected and Immunohistochemistry (IHC) assay was performed. The expression of ADH1A at RNA level in normal tissues and pan-solid tumors and the main functions of ADH1A in different solid tumors were analyzed by Bioinformatics mining. Results: At the RNA level, ADH1A was highly expressed in normal hepatocytes and was expressed lower in the tumor tissues than in the adjacent normal tissues or the corresponding normal tissues, suggesting the At the protein level, ADH1A was expressed to varying degrees in human alveoli, kidney, stomach, colon, and rectum. We predicted three major conserved functions of ADH1A, including angiogenesis, cell adhesion, and leukocyte migration function which might influence the prognosis of the immunotherapy and the immune response, and constructed an upstream regulation network of ADH1A and a downstream protein network. Besides, we also explored the functional differences of ADH1A in lung adenocarcinoma and lung squamous cell carcinoma and its effect on overall survival. And for investigating ADH1A, the BALB/c mice might be an option to consider in constructing an animal model of gastric cancer (GC), esophageal carcinoma (ESCA), liver hepatocellular carcinoma (LIHC), and pancreatic adenocarcinoma (PAAD). Conclusions: ADH1A has potential diagnostic and prognostic value in various solid tumors. Our findings highlight new avenues for further investigation of ADH1A biology process and provide a novel potential prognostic biomarker of immunotherapy.
A fork in the road: A mixed methods study exploring why older adults with acute myeloid leukemia choose different treatment paths.
Authors: Thomas William LeBlanc, Roland B. Walter, Loriana Hernandez, Lucy Morgan, Timothy Bell, Charlotte Panter, Francois Peloquin, Jasmine Healy, Adam Gater, Verna Welch, Karim Amer, Louise O'Hara, Ryan Hohman, Andrew Brown, Nigel Russell, Diana M. Merino, Neil Horikoshi, Dawn Maze
Journal: Journal of Clinical Oncology (2020)

7520 Background: Current treatment options for acute myeloid leukemia (AML) are diverse, including intensive chemotherapy (IC), low intensity therapy, best supportive care (BSC), and hospice care. Despite continued development of new therapies, recent data suggest that approximately 60% of older US patients remain untreated, but reasons for this are not well understood. By gathering insights from physicians, patients, and their family members, this study aims to better understand the factors that influence treatment decisions for adults with AML. Methods: Physicians in the US (n=4), UK (n=3) and Canada (n=3), and 15 US AML patient-family member dyads took part in one-on-one, 60-minute semi-structured interviews. Each participant rated a series of factors on a scale from 0 (not at all important) to 3 (very important) to determine their importance in treatment decision-making. Among the 15 adults with AML (&gt;65 years, not taking IC) interviewed thus far, 13 had not received any treatment. Additional interviews are scheduled in the UK and Canada with patients having varied treatment experiences (data will be available for presentation). Results: To date, findings highlight the key role perceptions of side effects and patient health play in treatment decision making. A fear of treatment side effects was the primary reason patients (n=9/13) opted not to receive treatment. For the 2/15 study patients who had received treatment, side effects were considered the worst part of their treatment experience. Physicians also stated patients on BSC would be more willing to take low intensity treatments if risks (e.g., side effects) were minimized. Patients (n=11/15), their family members (n=11/15), and physicians (n=10/10) agreed that patients’ health (including age and comorbidities) influenced if treatment was pursued. Additionally, US physicians suggested that some patients have little desire to pursue treatment, with patients’ perception of low intensity therapy having poor efficacy and proximity of care influencing their choice for BSC or hospice care. Further analysis will explore other factors influencing patients’ treatment decisions and differences among patients who receive treatment versus those who do not. Conclusions: The treatment decision-making process for older adults with AML is complex and multifactorial. Understanding factors that influence treatment decisions is important if drug developers and prescribers are to ensure the availability of therapies that better align with individual patients’ needs.
易误诊为消化系统病变的内分泌疾病
Authors: 卢琳, 陆召麟
Journal: BMJ (2010)

消化系统是多种内分泌激素作用的靶器官,故而内分泌疾病经常会引起消化系统症状,甚至以消化系统症状首发,容易误诊.现介绍一些常见内分泌疾病的消化系统症状表现,希望能对这些疾病的鉴别诊断有所提示。