tbuckley/cabot-search huggingface dataset:
Early mortality in children with cancer in the National Institution of Pediatrics, Mexico.
Authors: Karla Diaz Ramirez, Marta Zapata Tarres
Journal: Journal of Clinical Oncology (2020)

e19004 Background: Children cancer represents the first cause of mortality by disease worldwide. Early mortality is defined as death within the first four weeks since the patient’s admission to the hospital, and it is an indicator to evaluate attention quality. It is considered that early mortality rate must be less than 5% in acute lymphoblastic leukemias, although it is not standardized in solid tumors. The aim of this study was to evaluate the early mortality rate in a third level pediatric center. Methods: We have conducted a retrospective analysis of oncology patient records dating from January 2012 to April 2017 diagnosed and treated in the National Institute of Pediatrics in Mexico. Patients who died in the first four weeks from diagnosis were included in our study. Clinical characteristics were analyzed with an univariate analyses using measures of central tendency for quantitative data and proportions for qualitative. We used SPSS-20 for all analyses. Results: A total of 1500 patients were diagnosed with neoplastic disease at the Institute within 2012 and 2017, 34 (2.26%) of them had an early death. Median age of diagnosis was 5 years. Central nervous system (CNS) tumors were the predominant group associated to early mortality (23.5%), followed by hepatocarcinoma, acute lymphoblastic leukemia (ALL), neuroblastoma, diffuse intrinsic pontine glioma (DIPG), and Wilms tumor (5.9% each). 70.6% had metastatic disease at diagnosis. Main cause of death was progression of disease (60%), followed by infectious complications (35%). Only one patient was treated by palliative care. Conclusions: In spite of children cancer care innovations, early death rates are still high, mainly because of delay in diagnosis at advanced stages of the disease. Another important factor in low-middle income countries is treatment abandonment, which is higher in patients who live in precarious conditions and live in isolated communities and must travel long distances to get medical attention. As healthcare professionals from a low-middle income country, we still have a lot to do to prevent our patients early mortality.
A multi-center phase II study of toripalimab with chemotherapy in patients with EGFR mutant advanced NSCLC patients resistant to EGFR TKIs: Efficacy and biomarker analysis.
Authors: Shengxiang Ren, Jie Zhang, Yanqiu Zhao, Xiaoqian Mu, Jianying Zhou, Zhang Bao, Yun Fan, Yanjun Xu, Yongqian Shu, Renhua Guo, Xiaoqing Liu, Hong Wang, Helong Zhang, Lin Deng, Ningqiang Ma, Jianxing He, Yalei Zhang, Caicun Zhou
Journal: Journal of Clinical Oncology (2020)

e21618 Background: Immune checkpoint blocker (ICB) monotherapy showed a lack of response in advanced NSCLC patients with EGFR mutations. This Phase II study aimed to evaluate the efficacy and safety of toripalimab, a humanized PD-1 mAb plus platinum doublets chemotherapy in EGFR mutant advanced NSCLC patients, who developed resistance to 1 st /2 nd generation of EGFR TKIs and without T790M mutation. Methods: Patients received toripalimab (240 or 360 mg) intravenously combined with carboplatin (AUC = 5) and pemetrexed (500mg/m2) on day 1, Q3W, for up to 6 cycles, followed by toripalimab and pemetrexed maintenance until disease progression or unacceptable toxicity. Efficacy was evaluated every six weeks according to RECIST v1.1. PD-L1 expression (JS311 assay) and co-mutation status by whole exome sequencing were further analyzed. Results: From Apr 2018 to March 2019, 40 patients were enrolled from 8 centers in China. The median age was 57 years with 53% female, 57.5% EGFR exon19 deletion and 42.5% L858R mutation. By the cutoff date of Jan 2, 2020, 20 partial response and 15 stable disease were observed (ORR 50% and DCR 87.5%) with a median DOR of 7.0 months. The median PFS was 7.0 months and the median OS was still not reached. 52.6% (20/38) patients were PD-L1+ (TPS≥1%) and had numerically higher ORR (60% vs 39%, p= 0.33) and longer PFS (median 8.3 vs 5.7 months, p= 0.61) than PD-L1- patients. Co-mutations analysis revealed common genetic alternations including TP53 (79%), RB1 (18%), ERBB2 (15%), PIK2CA (12%), CDKN2A (12%), HDAC9 (12%) and MET (9%). Patients with TP53 co-mutation responded significantly better in ORR than TP53 wild type patients (62% vs 14%, p= 0.04) . Most frequent TRAE included leukopenia (78%), neutropenia (70%), anemia (70%), ALT elevation (48%), AST elevation (48%) and nausea (48%). Grade 3+ TRAE occurred in 55% patients, including neutropenia (43%), leukopenia (20%) and anemia (13%). Dose delay due to TRAE occurred in 40% patients while 10% patients discontinued treatment due to TRAE. Conclusions: Toripalimab in combination with chemotherapy showed promising anti-tumor activity with a manageable safety profile for advanced NSCLC patients with EGFR mutations refractory to TKI therapies. Patients with PD-L1+ tumor biopsy or TP53 co-mutation preferentially responded to the combination. A randomized phase III trial is ongoing to further validate the finding in this study (NCT03924050). Clinical trial information: NCT03513666.
Current situation of planned immunization in migratory children and its optimization analysis
Authors: 肖苑云, 林爱华
Journal: BMJ (2006)

我国已于1995年实现了以省、县、乡为单位儿童免疫接种率85%的目标,对儿童的健康成长起到了积极的保护作用[1].但是,随着社会经济的发展、变革,我国流动人口增至14 735万人,约占全国总人口的九分之一[2].流动儿童群体庞大、居无定所,预防接种工作难以落实,成为影响计划免疫工作持续深入发展的突出问题.作者对流动儿童的特征、计划免疫现状、影响因素及优化等方面进行分析。
右侧醛固酮瘤并肾上腺髓质不规则增生一例
Authors: 邵晋康, 王俊, 杨艳兰, 柳洁, 姜焕荣, 蔚锐传, 郭琴, 张乃珍, 张三德
Journal: BMJ (2006)

患者男,42岁.约6年前体检时发现高血压,未注意.近1个月出现间断头部憋胀症状伴高血压,血压呈持续性增高、阵发性加剧,常于情绪激动或精神紧张时发作,血压最高230/130 mm Hg(1 mm Hg=0.133 kPa),伴心悸,持续10～12 min可自行缓解,无头痛、头晕、恶心、视物模糊、大汗等,无小便时晕厥.平时血压(160～170)/110 mm Hg,先后口服卡托普利、苯磺酸左旋氨氯地平(施慧达)、美托洛尔(倍他乐克)及波依定等,血压控制不理想。
心血管影像学检查的合理应用
Authors: 赵世华
Journal: BMJ (2008)

随着科学技术的进步,医学影像学已经由过去单一的X线成像技术发展成为与计算机、电子学和医学生物工程技术等相结合的综合诊断体系.自20世纪80年代以来,心脏超声、CT(包括多排螺旋和电子束CT)、磁共振成像(MRI)、数字减影血管造影(DSA)、X线平片数字化包括计算机X线摄影(CR)和数字化X线摄影(DR)、放射性核素成像包括单光子发射CT(SPECT)和正电子发射体层摄影(PET)等影像学新技术的开发和应用,显著地改变了以X线平片和心血管造影为主体的普通心血管放射学的局面,从而共同构成了现代心血管影像学。
Significance of meflin-positive cancer-associated fibroblasts in predicting response to immune checkpoint inhibitors in non-small cell lung cancer.
Authors: Yuki Miyai, Atsushi Enomoto, Yuichi Ando, Masahide Takahashi
Journal: Journal of Clinical Oncology (2020)

3118 Background: Tumor immunity is regulated by complex interactions between cancer and immune cells, which also involves other components of the tumor microenvironment (TME). Recently, cancer-associated fibroblasts (CAFs), a major constituent of the TME, have emerged as important regulators of tumor immunity. Specifically, for example, α-smooth muscle actin or leucine-rich repeat containing 15-positive CAFs have been shown to be crucial for the suppression of tumor immunity. However, a comprehensive picture of how other CAF subset(s) are involved in tumor immunity is still lacking. Here, we show the involvement of a CAF subset highly expressing Meflin, which was recently identified as a marker of cancer-restraining CAFs in pancreatic cancer (Mizutani et al., Cancer Res, 2019), in the response of non-small cell lung cancer (NSCLC) patients to immune checkpoint inhibitors (ICIs). Methods: A sample cohort of 122 subjects with NSCLC who had received ICI monotherapy with nivolumab, pembrolizumab, or atezolizumab was identified at the Department of Respiratory Medicine at Nagoya University Hospital. We selected 92 eligible patients, collected formalin-fixed paraffin-embedded tumor tissues, and prepared 4–µm-thick slides for the analysis of Meflin expression by RNA-in situ hybridization assay, followed by the evaluation of treatment response of 88 patients using the iRECIST criteria. We assessed the number of Meflin-positive CAFs and divided the patients into Meflin-High (20% and more CAFs express Meflin) and -Low groups. The cut-off value was obtained by the ROC analysis. Primarily, objective response rate (ORR) was compared between Meflin-High and –Low groups. Overall survival (OS), and progression free survival (PFS) were also assessed. Results: Patients who started to receive ICIs till the end of March 2019 were enrolled and followed-up until the end of 2019. Analysis of the tumor tissues revealed that 24 (40.7%) of 59 Meflin-High patients responded to the ICI monotherapy. In contrast, none (0%) of 29 Meflin-Low patients showed any significant response (p-value: 0.0000174). Meflin-High groups showed statistically significant prolongations in both OS and PFS with the hazard ratios of 0.3114 [0.1591-0.6094] and 0.3997 [0.2290-0.6976], respectively. Conclusions: This retrospective observation indicated that the high infiltration of Meflin-positive CAFs may shape tumor-suppressive immune response and increase the sensitivity to ICIs, which differs from those of other CAF subsets.
Liquid biopsy: A community-based oncology practice experience.
Authors: Khalil Choucair, Bassam Ibrahim Mattar, Quoc Van Truong, Travis Lee Koeneke, Phu Van Truong, Christopher Dakhil, Michael W. Cannon, Seth Joel Page, Jeremy Michael Deutsch, Eric A. Carlson, Dennis Frederic Moore, Nassim H. Nabbout, K. James Kallail, Shaker R. Dakhil, Pavan S. Reddy
Journal: Journal of Clinical Oncology (2020)

3527 Background: Liquid biopsy is a promising and minimally invasive genetic test examining plasma circulating tumor DNA. Coupled with the rapidly developing next-generation sequencing (NGS) technologies, it holds the potential for implementation in selecting signal-matched therapeutic options. Methods: A retrospective chart review was conducted on adult patients with advanced solid tumors whose tumors were tested with Guardant360 assay, between December 2018 and December 2019. A total of 178 patients were referred for testing by 12 oncologists within a single community cancer center. Results: Referral rates varied widely (2.25% - 22%). The majority of patients (98%) were tested upfront for molecular marker evaluation, in either newly diagnosed advanced cancer patients, or in recurrent patients without enough tissue for testing. Other patients (2%) were evaluated after failure of 1 st line therapy to assess for acquired mutations. A total of 18 histological types were tested, with lung (LCa; n = 90; 50.56%), breast (BCa; n = 31; 17.42%), and colorectal (CRCa; n = 14; 7.87%) cancers being the most common types. In 86.11% of all tests (n = 180), ≥ 1 alteration was detected, while 13.89 % of tests did not reveal any tumor-related mutation, and were considered negative. The average number of alterations per test was 3.1 (±2.14; n = 481), and varied across types: CRCa (4.36), prostate cancer (2.73), BCa (2.97), and LCa (2.59), had the highest average number of alterations per test. Similarly, LCa (48.44%), BCa (19.13%), and CRCa (12.68%), harbored most of the detected somatic alterations (n = 481). Of all the alterations of practical significance (n = 457), TP53 (32.17%), PIK3CA (8.53%), EGFR (7.66%) and KRAS (7.22%), were the most commonly altered genes. Only 1 patient had a positive MSI-H status, amenable to immune-therapy. Of those with positive test results (n = 155), 31 (20%) had ≥ 1 FDA approved, target-matched therapeutic opportunity. Similarly, 71 patients (45.81%) had ≥ 1 target-matched therapeutic opportunity, outside current indications. Lastly, when no FDA-approved target-matched therapy was available (n = 39), results from liquid biopsy testing offered signal-based clinical trial opportunity in 39/39 patients. Conclusions: Implementation of NGS-based liquid biopsy testing is feasible within a community practice. In the era of precision oncology, such assays have the potential to expedite the efforts towards target-matched therapies and signal-based clinical trial opportunities. Further studies are warranted to identify the most-cost effective testing strategies.
Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: prospective observational study
Authors: Julie Toubiana, Clément Poirault, Alice Corsia, Fanny Bajolle, Jacques Fourgeaud, François Angoulvant, Agathe Debray, Romain Basmaci, Elodie Salvador, Sandra Biscardi, Pierre Frange, Martin Chalumeau, Jean-Laurent Casanova, Jérémie F Cohen, Slimane Allali
Journal: BMJ (2020)

To describe the characteristics of children and adolescents affected by an outbreak of Kawasaki-like multisystem inflammatory syndrome and to evaluate a potential temporal association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.Prospective observational study.General paediatric department of a university hospital in Paris, France.21 children and adolescents (aged ≤18 years) with features of Kawasaki disease who were admitted to hospital between 27 April and 11 May 2020 and followed up until discharge by 15 May 2020.The primary outcomes were clinical and biological data, imaging and echocardiographic findings, treatment, and outcomes. Nasopharyngeal swabs were prospectively tested for SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR) and blood samples were tested for IgG antibodies to the virus.21 children and adolescents (median age 7.9 (range 3.7-16.6) years) were admitted with features of Kawasaki disease over a 15 day period, with 12 (57%) of African ancestry. 12 (57%) presented with Kawasaki disease shock syndrome and 16 (76%) with myocarditis. 17 (81%) required intensive care support. All 21 patients had noticeable gastrointestinal symptoms during the early stage of illness and high levels of inflammatory markers. 19 (90%) had evidence of recent SARS-CoV-2 infection (positive RT-PCR result in 8/21, positive IgG antibody detection in 19/21). All 21 patients received intravenous immunoglobulin and 10 (48%) also received corticosteroids. The clinical outcome was favourable in all patients. Moderate coronary artery dilations were detected in 5 (24%) of the patients during hospital stay. By 15 May 2020, after 8 (5-17) days of hospital stay, all patients were discharged home.The ongoing outbreak of Kawasaki-like multisystem inflammatory syndrome among children and adolescents in the Paris area might be related to SARS-CoV-2. In this study an unusually high proportion of the affected children and adolescents had gastrointestinal symptoms, Kawasaki disease shock syndrome, and were of African ancestry.
Locoregional control, failure patterns and clinical outcomes in patients with stage III non-small cell lung cancers treated with chemoradiation and durvalumab.
Authors: Michael Offin, Narek Shaverdian, Andreas Rimner, Stephanie Lobaugh, Annemarie Shepherd, Charles B. Simone, Daphna Y. Gelblum, Abraham Jing-Ching Wu, Nancy Y. Lee, Mark G. Kris, Charles M. Rudin, Zhigang Zhang, Matthew David Hellmann, Jamie E. Chaft, Daniel Richard Gomez
Journal: Journal of Clinical Oncology (2020)

e21058 Background: Definitive concurrent chemoradiation (cCRT) and durvalumab is a standard therapy for patients with unresectable stage III non-small cell lung cancers (NSCLC). Data is limited on outcomes with this regimen outside of clinical trials. Local-regional control rates to date remain undefined. Methods: We reviewed patients with stage III unresectable NSCLC treated between November 2017 and February 2019 with cCRT. Patients that received at least one cycle of durvalumab were further assessed for 12-month progression free survival (PFS), overall survival (OS), and the incidence and pattern of local-regional and metastatic failures. Disease-relapse was characterized to determine patients potentially eligible for metastasis-directed ablative therapies. Toxicities leading to durvalumab discontinuation were evaluated using CTCAE v.5.0. Results: Of the 83 patients with stage III NSCLC treated with cCRT (median 60Gy), 62 received durvalumab and were evaluable (median follow-up: 12 months). Patients (n = 21, 25%) did not receive durvalumab largely related to metastatic progression (n = 9) or persistent cCRT toxicity (n = 10). In the 62 durvalumab treated patients the median age was 66 (range: 49 - 86), 73% had stage IIIB (n = 33) or IIIC (n = 12) disease, and 58% (n = 36) had adenocarcinoma. The median time from cCRT end to durvalumab start was 1.5 months. Patients received a median of 8 months of durvalumab; 35% (n = 22) of patients completed 12 months of therapy. Common reasons for discontinuing durvalumab included disease progression (32%, 20/62) and toxicity (24%, 15/62). The estimated 12-month PFS and OS were 65% (95% CI: 51 - 79%) and 85% (95% CI: 75 - 95%), respectively. High TMB (≥ 8.8 mt/Mb) or PD-L1 (≥ 1% or PD-L1 ≥ 50%) did not predict improved PFS. Patients who discontinued durvalumab due to toxicity did not have inferior PFS. The cumulative 12-month incidence of local-regional and distant metastatic failures were 18% (95% CI: 5.9 - 30%) and 30% (95% CI: 16.3 - 44.5%), respectively. Of the 17 patients with distant metastases, 9 had oligometastases and would have been potential candidates for comprehensive ablative therapies. Conclusions: Outcomes and toxicities outcomes with cCRT and durvalumab in clinical practice align with the PACIFIC trial. Analysis of disease-relapse suggests a substantial minority of patients with disease progression may be potential candidates for metastasis-directed therapies. Local regional outcomes appear improved to historical data of cCRT alone.
The role of autologous stem-cell transplantation in high-risk neuroblastoma consolidated by anti-GD2 immunotherapy: Results of 2 consecutive studies in a single referral institution.
Authors: Jaume Mora, Alicia Castañeda, Miguel Angel Flores, Vicente Santa-María, Moira Garraus, Maite Gorostegui, Margarida Simao, Sara Perez-Jaume, Salvador Mañe
Journal: Journal of Clinical Oncology (2020)

10539 Background: Treatment of high-risk NB within the major international cooperative groups (COG and SIOP) comprise intensive induction, consolidation with high dose chemotherapy and autologous stem cell rescue (ASCR) followed by anti-GD2 immunotherapy and isotretinoin as maintenance therapy. In the COG studies dinutuximab and cytokines (GM-CSF and IL-2) were used to treat patients in complete remission (CR) after ASCR whereas SIOPEN studies used dinutuximab-beta plus/minus IL-2 and included patients with responsive (no progression 109 days after ASCR) but refractory (skeletal metaiodobenzylguanidine positivity with three or fewer areas of abnormal uptake). Methods: Since December 2014, HR-NB patients referred to HSJD were eligible for consolidation with anti-GD2/GM-CSF immunotherapy in 2 consecutive studies (dinutuximab for EudraCT 2013-004864-69 and naxitamab for 017-001829-40) and naxitamab/GM-CSF compassionate use (CU) with or without prior ASCR. Patients were enrolled in 1st CR or with primary refractory bone/bone marrow (B/BM) disease. We accrued a study population of two groups whose consolidative therapy, aside from ASCR, was similar: anti-GD2 (dinutuximab or naxitamab) antibodies + GM-CSF and local radiotherapy. This is a retrospective analysis of their event-free survival (EFS) and overall survival (OS) calculated from study entry. Results: From Dec 14 til Dec 19, 67 study patients were treated with the COG (dinutuximab + GM-CSF+ IL-2 + RA) regimen (n = 21) in the HSJD-HRNB-Ch14.18 study or with Naxitamab and GM-CSF in the Ymabs study 201 (n = 12) or CU (n = 34). 23 patients were treated with primary refractory disease in the B/BM, and 44 in 1 st CR. The 67 study patients included 13 (19%) treated following single ASCR and 54 following induction chemotherapy and surgery. Median follow-up for all surviving patients is 16.2 months. Two-year rates for ASCR and non-ASCR patients were, respectively: EFS 64% vs. 54% (p = 0.28), and OS 66.7% vs. 84% (p = 0.8). For the 44 pts in 1 st CR, 2-year rates for ASCR and non-ASCR patients were, respectively: EFS 65% vs. 58% (p = 0.48), and OS 71% vs. 85% (p = 0.63). Conclusions: In this retrospective, single center study, ASCR did not provide survival benefit when anti-GD2 + GM-CSF based immunotherapy was used for consolidation after dose-intensive conventional chemotherapy.
布氏杆菌病一例
Authors: 马晶晶, 李明, 赵雪丽
Journal: BMJ (2008)

患者男,56岁.因发热3个月于2006年12月21日来诊.患者于2006年9月无明显原因出现持续性发热,最高38.6 ℃,逐渐出现双膝关节痛,伴消瘦,到当地医院给予头孢哌酮、丁胺卡那霉素(具体不详)治疗近2周,病情无好转。
营养性贫血与消化系统疾病
Authors: 陈嘉林
Journal: BMJ (2010)

营养性贫血从细胞形态方面主要分为两大类:小细胞低色素性贫血(即缺铁性贫血)和大细胞性贫血(即巨幼细胞贫血).营养性贫血除了可影响消化系统功能外,甚至可造成消化系统器质性损伤.同时,很多消化系统疾病也是引起营养性贫血的原因。
Detection of Insulinomas Using Dual-Time-Point 68Ga-DOTA-Exendin 4 PET/CT
Authors: Kerstin Michalski, Katharina Laubner, Christian Stoykow, Mohamed Aymen Omrane, Helmut R. Maecke, Jochen Seufert, Christian Goetz, Philipp T. Meyer, Juri Ruf
Journal: Clinical Nuclear Medicine (2020)

Purpose Insulinomas are predominantly benign neuroendocrine tumors originating from beta cells within the islets of Langerhans of the endocrine pancreas. Because surgical resection represents the only curative therapy option, exact tumor localization and discrimination of insulinomas from focal or diffuse manifestations of congenital hyperinsulinism are crucial for optimal treatment strategies. We investigated the diagnostic value of glucagon-like peptide 1 receptor PET/CT using 68 Ga-DOTA-exendin 4 for detecting insulinomas and compared the diagnostic value of PET scans performed at 2 time points. Methods In 10 patients with clinically and biochemically suspected insulinoma, PET/CT was performed at 1 hour (PET1) and 2 hours (PET2) after injection of 68 Ga-DOTA-exendin 4. In this retrospective analysis, tracer uptake was visually assessed in both scans by 2 independent readers. SUVmax and tumor-to-background ratio (TBR) of focal lesions were assessed. Imaging results were compared with histopathologic findings, if patients underwent resection. Results Increased focal 68 Ga-DOTA-exendin 4 uptake was observed in 8 of 10 patients concordantly by both readers. Seven patients with focal uptake underwent surgery with tumor enucleation and histopathologic proof of insulinoma (7/8). Two of 10 patients without focal uptake were considered to suffer from diffuse form of congenital hyperinsulinism and consequently received medical treatment. A significant increase of tumoral SUVmax on PET2 (PET1: SUVmax 20.2 ± 8.2 g/mL; PET2: SUVmax 24.7 ± 7.9 g/mL; P = 0.0018) did not result in a significant improvement in TBR (PET1: TBR 4.9 ± 1.7; PET2: TBR 4.3 ± 1.2; P = 0.2892). Conclusions Focal uptake of 68 Ga-DOTA-exendin 4 reliably indicated insulinomas as histopathologically confirmed in all patients undergoing consecutive surgery. The diagnostic value of PET2 was not found to be superior to PET1, indicating that a single 1-hour 68 Ga-DOTA-exendin 4 PET/CT scan is a sufficient and convenient approach for patient care.