tbuckley/cabot-search huggingface dataset:
Association of Internet Addiction With Nonsuicidal Self-injury Among Adolescents in China
Authors: Jie Tang, Ying Ma, Stephen P. Lewis, Ruoling Chen, Angela Clifford, Brooke A. Ammerman, Marufu Martin Gazimbi, Adrian Byrne, Yu Wu, Xinchuan Lu, Hongjuan Chang, Chun Kang, Henning Tiemeier, Yizhen Yu
Journal: JAMA Network Open (2020)

Both nonsuicidal self-injury (NSSI), defined as the direct, deliberate damage of one's body tissue without suicidal intent, and internet addiction among adolescents are public health concerns. However, the possible association of NSSI with internet addiction is not well understood.To examine the occurrence of internet addiction with NSSI and any sex differences among Chinese adolescents.A multicenter, cross-sectional, survey study was conducted from February 18 to October 15, 2015, among adolescents aged 11 to 20 years from 343 classes in 45 public high schools across 5 provinces of China. Data analysis was performed from August 1, 2018, to March 1, 2019.Possible internet addiction and internet addiction.Less-frequent (1-4 times) NSSI and more-frequent (≥5 times) NSSI were surveyed using the Chinese version of the Functional Assessment of Self-Mutilation.A total of 15 623 students (8043 male [51.5%] and 7580 female [48.5%]) aged 11 to 20 years (mean [SD] age, 15.1 [1.8] years) participated. Of these, 4670 participants (29.9%) met the criteria for possible internet addiction and 509 participants (3.3%) met the criteria for internet addiction. A total of 2667 students (17.1%) engaged in less-frequent NSSI, while 1798 students (11.5%) engaged in more-frequent NSSI in the 12 months preceding the survey. Both possible internet addiction and internet addiction were associated with less-frequent or more-frequent NSSI. The adjusted odds ratios were 1.29 (95% CI, 1.17-1.42) for possible internet addiction and 1.41 (95% CI, 1.11-1.80) for internet addiction for less-frequent NSSI; for more-frequent NSSI, the adjusted odds ratios were 1.75 (95% CI, 1.56-1.96) for possible internet addiction and 2.66 (95% CI, 2.10-3.38) for internet addiction. These associations were similarly observed among age groups of 11 to 14, 15 to 17, and 18 to 20 years. No sex disparities were found in the associations of internet addiction with NSSI, except among adolescents aged 11 to 14 years, where the odds ratios for possible internet addiction with less-frequent NSSI were higher in male adolescents (1.53; 95% CI, 1.25-1.88) than female adolescents (1.13; 95% CI, 0.90-1.47).Internet addiction appears to be associated with NSSI, and the findings of this study suggest that the association was similar between male adolescents and female adolescents. These data suggest that evaluation of the risk of NSSI for adolescents in association with internet addiction may help health care professionals in developing preventive interventions for NSSI.
Radiomics risk score (RRS) on CT to predict survival and response to CDK 4/6 inhibitors in hormone receptor (HR) positive metastatic breast cancer (MBC).
Authors: Siddharth Kunte, Nathaniel Braman, Kaustav Bera, Patrick Leo, Jame Abraham, Alberto J. Montero, Anant Madabhushi
Journal: Journal of Clinical Oncology (2020)

e13041 Background: The addition of CDK 4/6 inhibitors (CDK) to endocrine therapy (ET) is the standard of care for HR+ MBC. Currently, no robust predictive markers for CDK inhibitors exist. We hypothesized that baseline imaging features on pre-treatment CT scans using machine learning could correctly identify responders to CDK. Methods: From a retrospective pt registry, 46 pts with HR+ MBC who received palbociclib (palbo) plus ET and had liver metastases were identified, and divided at random into equally sized training and testing cohorts. Patients with objective response/stable disease per RECIST v1.1 were defined as ‘responders’ (65%), and those with progressive disease within 6 months were ‘non-responders’ (35%). The median age at diagnosis was 62. All pts were ER+ and 4% were HER2+. 65% pts received palbo as 1st or 2nd line tx. 503 radiomic texture features measuring subtle differences in lesion heterogeneity on a pixel level were extracted on pre-treatment CT within the first lesion measured for RECIST assessment. An elastic net Cox proportional hazards model was constructed within the training set to derive a Radiomics Risk Score (RRS), which was evaluated for association with prognosis and response within the testing set. A risk score threshold was chosen in the training set for stratifying patients into high and low risk groups. Results: The RRS consisted of 4 radiomic features indicating intratumoral heterogeneity to be associated with poor outcome. In the independent testing set (n = 23), RRS was continuously associated with survival (p = .0027) on multivariate analysis, along with age and RECIST response (Table). Categorical risk groups were similarly associated with survival in the testing set (p = .00491, HR = 4.03, CI = 0.6772). Median survival time in low and high risk groups were 2.33 and 0.673 years, respectively. When compared against RECIST response in the testing set, RRS was found to also be predictive of response with an ROC curve of 0.675. Conclusions: Radiomics analysis was able to predict response and survival in HR+ MBC pts prior to initiation of treatment with CDK. [Table: see text]
血清胃蛋白酶原、幽门螺杆菌抗体与胃黏膜病变的关系
Authors: 马颖杰, 刘凤奎, 王惠吉
Journal: BMJ (2007)

2005年5月至2006年10月北京友谊医院消化内镜中心行胃镜检查者276例,按病理诊断分组,设正常人对照12例.用免疫放射法定量测定血清胃蛋白酶原Ⅰ(PG Ⅰ)、PGⅡ,定性分析血清抗幽门螺杆菌IgG抗体,计算PGⅠ/PGⅡ(PGR).结果 正常人对照PG Ⅰ为(146±40)μg/L,慢性浅表性胃炎组PG Ⅰ为(149±62)μg/L,慢性萎缩性胃炎、胃癌组PGI、PGR降低,消化性溃疡组PGⅠ、PGⅡ升高.幽门螺杆菌感染与PG水平的变化有关.PG水平异常患者应进一步行胃镜检查。
A clinical study of tremelimumab alone or in combination with olaparib in patients with advanced epithelial ovarian cancer.
Authors: Stephanie Gaillard, Maureen Berg, Jeanne Harrison, Peng Huang, James M. Leatherman, Michele Doucet, Rupashree Sen, Aditya Suru, Hongyan Cai, Jennifer N. Durham, Danijela Jelovac, Ashley Cimino-Mathews, Sudipto Ganguly, Leisha A. Emens
Journal: Journal of Clinical Oncology (2020)

6045 Background: Single agent immunotherapy (IO) has shown only modest clinical activity for the treatment of ovarian cancer. The combination of anti-programmed death-1 and PARP inhibitors showed promising activity in early trials. Here, we report the results of an open-label, parallel arm, dose escalation study of tremelimumab (T) alone or in combination with olaparib (O) in patients (pts) with advanced epithelial ovarian cancer (EOC). Methods: Pts with recurrent/persistent EOC who had progression &lt; 12 months from last platinum exposure were enrolled. Prior therapy with IO (except anti-CTLA-4) or PARP inhibitor was allowed. Pts were randomized to either T 10mg/kg every 4 weeks (wks) x 7 then every 12 wks (Arm A) or T with O twice daily at three planned dose levels (Arm B). The primary objectives were safety, pharmacodynamic (PD) change in CD4 + ICOS hi peripheral T cells by flow cytometry, and identification of the optimal dose combination of T with O. Secondary objectives included 6-month progression-free survival (PFS6) and objective response rate (ORR). Results: A total of 24 pts were treated, 12 on Arm A, and 12 on two Arm B dose levels. Pts had a median age of 60 years (range 44-81). Histologic subtypes included high-grade serous EOC (20 pts, 83%), clear cell (3 pts, 13%), and moderately-differentiated adenocarcinoma (1 pt, 4%). BRCA1 mutation (mt) was present in 2 cases, BRCA2 mt in 1. Median number of prior regimens was 3.5 (range 1-9). Most adverse events (AEs) were attributable to T, the most common grade 3 toxicities were rash (13%), immune-mediated hepatitis (8%), and colitis (8%). No grade ≥4 toxicities were identified. Immune-mediated AEs also included acute kidney injury, hypophysitis, and hypothyroidism. No dose limiting toxicities were identified on Arm B. Two pts in Arm B had &gt;PFS6. Of 20 pts evaluable for response, there was 1 partial response (Arm B), and 9 pts had stable disease (6 on Arm A, 3 on Arm B). Mean percentage of CD4+ICOS hi T cells was significantly increased on Days 15 and 22 compared to Day 1 at both T dose levels (Table).T at 3 mg/kg with O at 150mg is the optimal dose of those tested. Conclusions: T and T with O was tolerable, with modest clinical activity in this pt population. AEs were as expected, and peripheral CD4 + ICOS hi T cells increased on therapy. Clinical trial information: 02485990. [Table: see text]
腹胀-发热-腹腔积液
Authors: 于鹏, 韩潇, 吴东
Journal: BMJ (2012)

患者男,63岁,因腹胀40 d、发热2周,收入北京协和医院消化科.腹胀是临床常见的症状,引起腹胀的机制包括腹水、空腔脏器牵拉、肝脾肿大等.腹胀病因可以是消化系统异常,也可是非消化系统疾病. 关键词：腹腔积液;结核性腹膜炎
A phase II study to evaluate the need for &gt; two doses of nivolumab + ipilimumab combination (combo) immunotherapy.
Authors: Michael A. Postow, Debra A Goldman, Alexander Noor Shoushtari, Allison Betof Warner, Margaret K. Callahan, Parisa Momtaz, Ellesa Naito, Omar Eton, Suresh Nair, Jedd D. Wolchok, Katherine Panageas, Paul B. Chapman
Journal: Journal of Clinical Oncology (2020)

10003 Background: Standard of care nivolumab (nivo) + ipilimumab (ipi) combo immunotherapy is given for 4 doses in patients (pts) with unresectable stage III/IV melanoma. Whether 4 doses are needed is questionable as retrospective data suggest pts treated with &lt;4 doses of combo due to toxicity can have durable benefit. No prospective trials have evaluated the efficacy of intentionally giving &lt;4 doses of combo in unresectable stage III/IV melanoma. Methods: In this phase 2, multicenter clinical trial (n=60), pts with unresectable stage III/IV melanoma received 2 doses of nivo (1mg/kg) + ipi (3mg/kg) followed by a CT scan at week 6. Pts with complete (CR) or partial responses (PR) by RECIST 1.1 or stable disease without an increase in total measurable tumor burden had protocol defined early favorable anti-tumor effect (FATE) and ceased combo, transitioning to maintenance nivo. Pts without FATE at week 6 received the standard third and fourth doses of combo followed by maintenance nivo. The primary endpoint was response rate by RECIST 1.1 at week 12. Secondary endpoints included additional efficacy assessments and safety. Results: 41 pts (68%) had FATE at week 6. The best overall response rates (CR + PR) by RECIST at week 12 or any time afterwards were 48% (95% CI: 35.2-61.6%) and 53% (95% CI: 40.0-66.3%), respectively. 18%, 58%, 12%, 10% had 1, 2, 3, 4 doses of combo, respectively. With a median follow-up of 11 months, any grade treatment-related toxicity occurred in 100% (57% grade 3-4) of pts. Three pts died due to treatment-related toxicity (2 myocarditis, 1 possible adrenal insufficiency). Among the 19 pts without FATE at week 6 and not selected to de-escalate combo after dose 2, no pts ultimately responded with ongoing combo dosing. Conclusions: The first 2 doses of nivo + ipi appear to drive combo’s response efficacy and toxicity. Early radiographic imaging at week 6 may be able to identify pts who do not respond to combo dosing beyond dose 2. Randomized studies are planned to evaluate 1 dose of combo to see if efficacy is maintained with reduced toxicity. Clinical trial information: NCT03122522.
Prospective review of SPEP orders confirms need for testing algorithm.
Authors: Sandra Ann Mazzoni, Amarendra Kumar Neppalli, Shadi Khalil, Bakos Jonahtan, James Kalmuk, Georges El Nahas, Alexander Bray, Christine Litwin, Charles Greenberg
Journal: Journal of Clinical Oncology (2020)

e19326 Background: Serum protein electrophoresis (SPEP) identifies monoclonal proteins associated with plasma cell disorders including multiple myeloma. There are no large prospective studies looking at clinical ordering patterns of SPEPs. This study will determine the percent of monoclonal proteins detected by SPEP testing and factors that are or are not associated with identifying monoclonal proteins. We predict that SPEP testing is commonly ordered and not thoroughly evaluated prompting a need for an algorithm to ensure appropriate use and follow up testing. Methods: In our academic center, we captured data on all SPEP tests ordered from March 17 to June 16, 2019. We chart reviewed each associated patient to collect the following: patient age and sex, SPEP result, hemoglobin, serum albumin, total serum protein, serum calcium, serum creatinine, presence of proteinuria, serum free light chains, immunoglobulins (IgG, IgA, IgM), serum immunofixation, urine protein electrophoresis, urine immunofixation, bone marrow biopsy report, imaging results (bone survey, PET, MRI) and echocardiograms. We ascertained the reason for ordering the SPEP, inpatient or outpatient status of the patient and the ordering department. Results: There were 929 SPEPs ordered. 410 (44%) ordered on “new” patients with no previously identified M-spike. Of the 410 “new” SPEP orders, 57 (14%) detected a M-spike. 8 (2%) led to a diagnosis requiring treatment: 7 new cases of myeloma and 1 case of AL amyloidosis. 108 (26%) of the 410 “new” SPEP orders were ordered in the inpatient setting with 20 “new” M-spikes identified. Only 4 of the 108 inpatient SPEP orders identified a diagnosis requiring treatment—4 cases of myeloma. These patients had SPEPs ordered due to pathologic fractures related to lytic lesions and acute renal failure with other associated CRAB features. Neurologic findings were the most common reason for ordering “new” SPEPs, 106 (26%) of the 410 with only 7 with M-spike—all low risk MGUS. Only 2 of 26 patients were found to have low risk MGUS when SPEP was ordered as part of a rheumatologic work up. All 6 patients with SPEP ordered for dermatologic reasons were negative for M-spike. 23 (40%) of the 57 “new” M-spikes had no follow up testing to determine the clinical significance. Conclusions: This prospective review on the use of SPEP orders in an academic medical center documents the need to provide an algorithm to aide effective use of testing to decrease inpatient ordering and provide guidance on appropriate follow up testing. We found a very low yield with SPEP testing for neurologic, rheumatologic and dermatologic reasons.
Research progress on diagnosis and treatment of gastrointestinal endoscopy in pregnancy
Authors: Wenming Wu, Zheng Yuan, Ziqin Sun
Journal: BMJ (2016)

Gastrointestinal endoscopy plays a major diagnostic and therapeutic role in most gastrointestinal disorders. However, limited data of clinical safety is available in pregnant patients. Large studies, preferably prospective, with follow-up of fetal outcome are needed to determine fetal safety of endoscopy. This article briefly analyzed the literature on the research progress of gastrointestinal endoscopy during pregnancy, which offered an evident base for diagnosis and treatment in digestive diseases.


Key words: 
Pregnant women; Digestive system diseases; Endoscopy, digestive system
Efficacy and safety of immune checkpoint inhibitors (ICIs) in unresectable hepatocellular carcinoma (HCC): A systematic review and meta-analysis of randomized clinical trials (RCTs).
Authors: Alexandre A. Jácome, Ana Carolina Guimaraes De Castro, João Paulo Solar Vasconcelos, Maria Helena Cruz Rangel Silva, Marco Antonio Oliveira Lessa, Eduardo Dias de Moraes, Aline Chaves Andrade, Barbara Sodre Figueiredo Ferreira, Frederico M. T. Lima, Marcela Lima Bulcao, Artur Rodrigues Ferreira, Joao Paulo Fogacci De Farias, Gabriel Prolla, Bernardo Garicochea
Journal: Journal of Clinical Oncology (2020)

e16631 Background: ICIs have ushered a new era in cancer therapy, but their efficacy in HCC is uncertain. Single-arm phase II studies with sorafenib-refractory patients have suggested clinical activity of nivolumab and pembrolizumab, which have become FDA-approved therapies. Nevertheless, the overall effect of ICIs compared with the standard of care (SOC) in unresectable HCC patients is still unknown. Methods: We systematically searched PubMed, Cochrane Library, Web of Science, LILACS, and ASCO and ESMO Meeting Proceedings in the last 10 years for RCTs that have compared the efficacy of ICIs versus the SOC in the systemic therapy of unresectable HCC. Outcomes of interest included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade 3-4 treatment-related adverse events (TRAEs). A summary hazard ratio (HR) of OS and PFS was calculated using 95% confidence intervals (CI) by fixed-effects model. The likelihood of ICIs being associated with ORR and TRAEs was expressed by odds ratio (OR) and 95% CI using a random-effects model (PROSPERO ID 162599). Results: Of the 2,334 studies yielded by the search, 3 studies were retained (KEYNOTE-240, CheckMate-459, and IMbrave150), totaling 1,657 patients (985 ICIs versus 672 SOC). Two studies compared ICIs versus sorafenib in 1 st line setting, and one study compared with placebo in 2 nd line. The ICIs studied were pembrolizumab, nivolumab, and atezolizumab. RCTs with anti-CTLA4 have not been reported. Two studies evaluated ICIs as monotherapy, and one study investigated the association with bevacizumab. Compared with the SOC (sorafenib in 1 st line or placebo in 2 nd line), ICIs significantly improved OS (HR: 0.78, 95% CI 0.68 – 0.89, p = 0.0002), PFS (HR: 0.79, 95% CI 0.71 – 0.89, p &lt; 0.0001), and ORR (OR: 2.82, 95% CI 2.02 – 3.93, p &lt; 0.0001). ICIs were associated with a lower probability of grade 3-4 TRAEs when compared to sorafenib (OR: 0.44, 95% CI 0.20 – 0.96, p = 0.04). No significant heterogeneity was found among studies when OS and ORR were analyzed, but it was found in the analysis of PFS and TRAEs. Conclusions: ICIs demonstrated superior efficacy and safety compared to the standard therapy of patients with unresectable HCC. The analysis of ICIs as monotherapy and combination therapy increased the heterogeneity among studies. The association of anti-angiogenic therapy with ICIs improved the survival benefit of immunotherapy and should become the new SOC in the 1 st line systemic therapy of unresectable HCC.
Mutational landscape and tumor mutation burden (TMB) feature of biliary cancer.
Authors: Bin Yi, Lianke Liu, Jinghai Song, Yingying Huang, Min Zhang, Rongrong Chen, Xuefeng Xia, Xiaoqing Jiang
Journal: Journal of Clinical Oncology (2020)

e16670 Background: Biliary cancer are relatively rare, highly aggressive and have poor prognoses. Most biliary cancers are diagnosed in the advanced and metastatic stages. Chemotherapy is the main treatment of advanced biliary cancer. We focus on gene mutation and tumor mutation burden (TMB) of biliary cancer. Methods: We retrospectively reviewed one hundred and fifty-six cases of biliary cancer. One hundred and fifty-six tumor tissues and 35 plasma samples were subjected to next-generation sequencing (NGS), which enables simultaneously assess snv, indel, rearrangements and cnv variations at least 59 genes (range 59-1021 genes). Results: Fifty-eight patients were intrahepatic cholangiocarcinoma (IHCC), 50 were extrahepatic cholangiocarcinoma (EHCC) and 48 were gall bladder cancer (GBC). From tissue samples, the commonly mutated genes were different in three groups. TP53 was the most frequently mutated gene among the three groups (IHCC 43%, EHCC 58%, GBC 79%). KRAS (33%), TERT (16%), LRP1B (16%), IDH1/2 (10%) were usual in IHCC. KRAS (28%), SMAD4 (20%), STK11 (18%), ARID1A (12%) were usual in EHCC. And ERBB2 (19%), LRP1B (17%), TERT (15%), MLL3 (15%) were usual in GBC. TP53, LRP1B and MLL3 had a higher frequency in GBC than cholangiocarcinoma (p &lt; 0.05), and KRAS was more common in cholangiocarcinoma than GBC (p &lt; 0.05). 72.4% IHCC, 76.0% EHCC and 60.4% GBC had gene mutation associated with target therapies, which involved in multiple signal pathway, such as IDH1/2, FGFR, ERBB1/2/3, MET, PIK3CA, PTEN, BRCA, etc. Thirty-five patients had paired tissue and plasma samples, 21 stage Ⅲ/Ⅳ, 11 stage Ⅱ and 3 unknown. The concordance between tissue and plasma was 53% in all patients and was higher in stage Ⅲ/Ⅳ than stage Ⅱ (p &lt; 0.05). One hundred and thirty-three tissue samples assessed TMB, the mean TMB was highest in the GBC group, followed by EHCC and IHCC (7.1 vs 5.5 vs 3.9 muts/Mb, p &lt; 0.05). The proportion of TMB-H (defined 9.0 muts/Mb as cutoff value) was higher in GBC than IHCC and EHCC. Conclusions: IHCC, EHCC, and GBC have distinctive mutational landscapes and TMB features. It maybe guide different target therapy and immunotherapy strategies in the clinic. ctDNA has promising potential in biliary cancer.
Effect of pembrolizumab (pembro) on hepatitis B viral (HBV) load and aminotransferase (ALT) levels in patients (pts) with advanced hepatocellular carcinoma (aHCC) in KEYNOTE-224 and KEYNOTE-240.
Authors: Stephen Lam Chan, Andrew X. Zhu, Richard S. Finn, Julien Edeline, Sadahisa Ogasawara, Jennifer J. Knox, Bruno Daniele, Baek-Yeol Ryoo, Philippe Merle, Mohamed Bouattour, Ho-Yeong Lim, Yee Chao, Thomas Yau, Barbara Anne Haber, Usha Malhotra, Chih-Chin Liu, Masatoshi Kudo, Ann-Lii Cheng
Journal: Journal of Clinical Oncology (2020)

4587 Background: The effect of PD-1 inhibition on HBV infection is unclear, and pts with HBV are often excluded from trials. This analysis evaluated HBV viral load and liver function (ALT levels) in pts with HBV infection in 2 trials of pembro: KEYNOTE-224 and KEYNOTE-240. Methods: Eligible pts with aHCC post first-line sorafenib and controlled HBV received pembro 200 mg IV Q3W until progression. Pts with active HBV (HBsAg positive and/or HBV DNA detectable) and inactive HBV (anti-HBc positive, HBsAg negative, and HBV DNA not detectable) at baseline (BL) were included. Results: Of 104 pts in KEYNOTE-224 and 413 pts in KEYNOTE-240, 8 (7.7%) and 101 (24.5%) had active HBV and 13 (12.5%) and 102 (24.7%) had inactive HBV, respectively. All pts with HBV received nucleos(t)ide analogs. In KEYNOTE-240, 2 (2.8%) pts with active HBV in the pembro arm and 1 (3.4%) in placebo (pbo) had a &gt; 1 log increase (incr) of HBV DNA and 1000 IU/mL over BL; none in the pembro arm were associated with ALT elevation. No pts with inactive HBV in KEYNOTE-240 and no pts in KEYNOTE-224 had a &gt; 1 log incr and 1000 IU/mL over BL. No pts in KEYNOTE-224 and 28 (38.9%) with active HBV and 1 (1.4%) with inactive HBV in the pembro arm, and 8 (27.6%) with active HBV and 0 with inactive HBV in the pbo arm in KEYNOTE-240 had a &gt; 1 log decrease (decr) in HBV DNA. Conclusions: Few pts with aHCC and HBV had viral load incr with pembro. In KEYNOTE-240 no clinically meaningful differences between pembro and pbo were observed. ALT elevation was not associated with viral load incr with pembro. These data suggest that pembro is unlikely to significantly affect underlying HBV infection in pts with aHCC receiving HBV antiviral therapy. Clinical trial information: KEYNOTE-224, NCT02702414; KEYNOTE-240, NCT02702401 . [Table: see text]
胃食管反流的诊断及治疗
Authors: 李辉
Journal: BMJ (2012)

胃食管反流是一种较常见的食管疾病,但在我国并未引起应有的重视,绝大多数病例被忽略而得不到正确的诊断和治疗,甚至少数病例被误诊而进行错误的治疗.本文介绍胃食管反流的主要症状、诊断和治疗策略。