tbuckley/cabot-search huggingface dataset:
Clinical significance of brain metastases in patients with bronchopulmonary neuroendocrine tumors: A population-based analysis.
Authors: Harry E Fuentes, Mojun Zhu, Jennifer Gile, Konstantinos Leventakos, Mohamad Bassam Sonbol, Steven E. Schild, Jason Scott Starr, Thorvardur Ragnar Halfdanarson, Julian R. Molina
Journal: Journal of Clinical Oncology (2020)

e21575 Background: The clinical significance of brain metastases in patients with bronchopulmonary neuroendocrine (NE) tumors is unknown; we therefore conducted a population based analysis to evaluate the implications of brain metastases in these patients. Methods: The NCDB database was queried to identify patients with stage IV bronchopulmonary NE tumors treated between the years of 2004-2012. Patients were split into two groups based on the presence of brain metastases at diagnosis and survival probabilities with multivariate models were performed. Results: A total of 7,725 patients with Stage IV bronchopulmonary NE tumors were identified. The histological subtypes studied in this cohort were NE carcinoma (65.4%), large cell NE carcinoma (30.5%), typical carcinoid (2.8%) and atypical carcinoid (1.3%) . The patients included in this study were mainly white (86.4%) men (56.8%) with a median age of 67 years who had liver (9.5%), bone (6.2%) and brain (5.9%) metastases at diagnosis. The median overall survival (OS) of the cohort was 5.59 (95% CI: 5.4-5.8) months, but when OS was stratified by histological subtype it was significantly better in patients with typical carcinoid (table). In the whole cohort, the median OS did not differ between patients with and without brain metastases (5.55 vs. 5.68; p = 0.24). However, a sensitivity analysis by histology showed that the presence of brain metastases worsen the median OS of patients with typical carcinoid only (15.1 vs 4.6, p = 0.04). An adjusted multivariate analysis restricted to patients with brain metastases showed that administration of systemic chemotherapy (HR:0.5; 95% CI:0.35-0.72, p &lt; 0.001) and resection of distant metastases (HR:0.5; 95% CI:0.29-0.88, p = 0.017) were the two most powerful independent prognostic factors. Conclusions: The presence of brain metastases negatively impact survival of patients with typical carcinoids but not in those with the other histological subtypes included in this study. Staging MRI should be strongly considered at diagnosis in patients with bronchopulmonary NE tumors, due to the sizable proportion of these patients presenting with brain metastases and also due to its prognostic value in a subset of this population. [Table: see text]
Phase II randomized trial of first-line pembrolizumab and vorinostat in patients with metastatic NSCLC (mNSCLC).
Authors: Andreas Nicholas Saltos, Tawee Tanvetyanon, Ben C. Creelan, Michael Rahman Shafique, Scott Joseph Antonia, Eric B. Haura, Hong Zheng, Margaret Barlow, James Saller, Anna Castellano-Fornelli, Antoine Richards, Ram Thapa, Theresa A. Boyle, Dung-Tsa Chen, Amer A Beg, Jhanelle Elaine Gray
Journal: Journal of Clinical Oncology (2020)

9567 Background: Histone deacetylase inhibitors may enhance tumor immunogenicity through various mechanisms including induced expression of T cell chemokines. A previous phase I trial demonstrated the combination of pembrolizumab (P) with vorinostat (V) in mNSCLC was well tolerated with signals of activity in ICI-pretreated pts. We initiated a randomized trial in the first-line setting with the primary objective to determine if the combination had superior ORR compared to pembrolizumab monotherapy. Methods: Pts with treatment-naïve mNSCLC and PD-L1 expression ≥ 1% were eligible. Pts were randomized open-label 1:1 to receive P 200 mg IV q3 wk as monotherapy [Arm A] or P 200 mg IV q3 wk plus V 400 mg PO daily [Arm B]. The primary endpoint was overall response rate (ORR). Secondary endpoints included DOR, PFS and OS. Tumor biopsies were collected both pre- and on-treatment (day 15-21) for analysis of CD8+ TIL, scored using a 0-3 scale in tumor beds. Here we report results after a preplanned interim analysis for efficacy, with accrual ongoing to a planned total of 39 patients per arm. Results: Between 7/2017 – 1/2019, 49 pts were enrolled, with 47 pts evaluable for response (24 in Arm A and 23 in Arm B). Median age was 69 (range 47 - 87), 49% female, ECOG PS 0/1 in 11%/89%. PD-L1 TPS was ≥50% in 13/24 (54%) of pts in Arm A, and in 13/23 (57%) of pts in Arm B. The most common TRAEs in Arm A included diarrhea (13%), fatigue (8%), and pruritus (8%). 3 pts in Arm A experienced grade ≥ 3 irAEs (including 1 each of grade 3 hepatitis, pneumonitis, and rash). The most common TRAEs in Arm B included anorexia (43%), fatigue (43%), nausea (35%) and increased creatinine (35%). 1 pt in Arm B experienced grade ≥ 3 irAE (1 grade 3 pneumonitis). Pre-treatment CD8+ TIL were not significantly different between Arm A and Arm B (p = 0.85) with the majority of tumors in both arms having a low TIL score of 1 (65% Arm A and 73.7% Arm B). A significant increase from pre-treatment to on-treatment TIL scores was seen in both Arm A (p = 0.001) and Arm B (p = 0.002). The ORR in Arm B pts with low pre-treatment TIL (score = 1) pts was substantially higher (66.7%) than in Arm A (33.3%), suggesting the combination may be especially beneficial against low TIL tumors. Conclusions: The combination arm had a considerably higher ORR compared to pembrolizumab monotherapy, with a manageable toxicity profile. The combination of pembrolizumab plus vorinostat in mNSCLC warrants further investigation. Clinical trial information: NCT02638090 . [Table: see text]
鼻内镜手术治疗儿童慢性鼻窦炎78例临床分析
Authors: 张勤修, 邹建, 刘世喜, 覃刚, 安会明
Journal: BMJ (2006)

本文回顾性分析了78例儿童慢性鼻窦炎鼻内镜手术治疗的临床资料.其中治愈32例(41.0%),好转39例(50.0%),无效7例(9.0%),总有效率为91.0%,提示鼻内镜鼻窦手术是治疗儿童慢性鼻窦炎的有效方法。
婴幼儿反复咳嗽、发热伴肝脾肿大一例诊治体会
Authors: 闫莉, 代继宏, 黄英
Journal: BMJ (2012)

报道一例反复咳嗽、发热伴肝脾肿大婴幼儿确诊X连锁严重性联合免疫缺陷病过程,该病预后不良,如不给予造血干细胞移植则常于幼年夭折.提示,对XL-SCID应早期诊断,及早给予特异性治疗和提供遗传咨询非常重要。
The impact of surgery induced immune-nutritional change on the outgrowth of micrometastasis after potentially curative resection for gastric cancer.
Authors: Masaki Aizawa, Hiroshi Yabusaki, Atsushi Matsuki, Takeo Bamba, Satoru Nakagawa
Journal: Journal of Clinical Oncology (2020)

e16581 Background: Whereas radical resection for gastric cancer is only life-saving option, resulting host response have been suggested to trigger the outgrowth of previously disseminated foci at distant anatomical sites via alteration of anti-tumor immunity. The prognostic nutrition index (PNI) which was calculated as 10 × serum Alb concentration (g/dL) + 0.005 × peripheral total lymphocyte count (/µL) is a surrogate marker of inflammation related nutritional decline and the imbalance of T lymphocyte differentiation. The aim of study was to evaluate the impact of perioperative change of PNI. Methods: The medical record of 567 gastric cancer patients who matched with the following inclusion criteria, R0 resection between 2006 and 2018, no preoperative anticancer treatment, pStage IB-IIIC according to UICC TNM classification and no other organ cancer at surgery, was identified from the prospectively maintained database. The postoperative laboratory data was routinely evaluated at POD 1, 3, 7 and first visit after discharge (AD). The PNI was compared through the perioperative course. Then the predictive value of low PNI-AD which defined as PNI &lt; 40 on the relapse free survival (RFS) after surgery was estimated by COX proportional hazards analysis. Results: The median value of PNI at base line, 1, 3, 7 POD and AD was 51.0, 35.9, 34.0, 38.3 and 48.2, respectively. The PNI as significantly decreased at 1, 3 and 7 POD. Though the PNI at AD had a proclivity to recover, which was still significantly lower than that at base line. During observation period after surgery, the recurrence was encountered in 80 patients. The 5-year RFS rate in patients of pStage IB (n = 164), II (n = 228) and III (n = 175) was 97.4%, 88.9% and 64.7%, respectively. The multivariate analysis identified female gender (HR: 1.715, 95%CI; 1.018-2.890, p = 0.04), pT3-4 (HR:3.620, 95%CI; 2.011-6.518, p &lt; 0.01), pN1-3 (HR:2.741, 95%CI; 1.428-5.263, p = 0.02), vessel invasion (+) (HR:2.666, 95%CI; 1.681-4.229, p &lt; 0.01), PNI-AD &lt; 40 (HR:1.833, 95%CI; 1.002-3.352, p = 0.04) were independent predictors of recurrence. The low PNI-AD was significantly related to the recurrence in the population of pStage III, but not in pStage IB and II. Conclusions: The retardation of postoperative recovery of PNI might evoke the distant metastasis.
Recent progress in clinical significance of detection indicators of hepatitis B virus
Authors: 刘建军, 吴晓英
Journal: BMJ (2005)

随着人们对乙型肝炎(乙肝)研究的不断深入,乙肝病毒(HBV)指标检测结果的临床意义已发生了深刻变化,如果不改变过去对HBV检测指标的认识,就不能正确指导HBV感染及乙肝的诊断与治疗,现就血清HBV检测指标与临床关系的研究综述如下。
A phase II trial of nivolumab (NIVO) + palbociclib (PAL) + anastrozole (ANA) in postmenopausal women and men with estrogen receptor (ER)+/human epidermal growth factor 2 (HER2)- primary breast cancer (BC): CheckMate 7A8.
Authors: Sara M. Tolaney, Guy Jerusalem, Roberto Salgado, Xiaochun Liu, Tian Chen, Hongxia Zhang, Mustimbo Roberts, Dimitrios Zardavas, Aleix Prat
Journal: Journal of Clinical Oncology (2020)

TPS1105 Background: Cyclin-dependent kinase 4/6 (CDK 4/6) inhibition coupled with ER signaling blockade is an efficient treatment approach for patients (pts) with metastatic hormone receptor-positive, HER2− BC. Preclinical data suggest synergistic activity of CDK 4/6 inhibition and PD-1 blockade; in a syngeneic mouse tumor model, improved efficacy and complete tumor regression were observed with phased administration of ABE + PD-L1 therapy. Methods: CheckMate 7A8 (NCT04075604) is a randomized, noncomparative, multicenter, phase 2 study evaluating PAL + ANA +/- NIVO in postmenopausal pts with ER+, HER2− primary BC. After determining safe doses for NIVO combination regimens in the safety run-in phase, pts will be randomized in a 4:4:3 ratio to 1 of 3 treatment arms (Table) stratified by PD-L1 expression, node status and tumor size. Following treatment, all pts will undergo surgery and safety follow-up. Eligible pts are postmenopausal women and men with newly diagnosed, untreated, histologically confirmed ER+, HER2− BC with primary tumor ≥ 2 cm; suitable for neoadjuvant endocrine monotherapy and surgery; ECOG PS of 0–1; have baseline tumor tissue available; willing to undergo on-treatment research biopsy and tissue collection at surgery. Primary endpoints are number of pts with occurrence of dose-limiting toxicity (safety run-in phase) and residual cancer burden 0–I rate by central assessment at time of definitive surgery (randomized phase). Secondary endpoints include safety and tolerability, pathologic complete response, objective response rate and breast-conserving surgery rate. Key exploratory endpoints include biomarkers indicative of pharmacodynamic changes and potentially predicting treatment sensitivity. Interim analyses are planned. The study is currently enrolling. Clinical trial information: NCT04075604 . [Table: see text]
Characteristics and factors affecting mortality of patients admitted for chemotherapy in the United States during the year 2017.
Authors: Arya Mariam Roy, Manojna Konda, Akshay Goel, Rashmi Verma
Journal: Journal of Clinical Oncology (2020)

e19025 Background: Over the past two decades, there has been a tremendous increase in the chemotherapy options available to cancer patients. In terms of overall, progression-free survival, and temporary suppression of cancer-related symptoms, chemotherapy has shown beneficial effects. However, the side effects of chemotherapy are sometimes life threatening which affects an individual’s physical health, emotional state and quality of life. There is a considerable increase in the prevention, early identification and timely management of toxicities associated with chemotherapy; however, chemotherapy-related deaths still occur. Methods: We conducted a retrospective analysis of the National Inpatient Sample Database for the year 2017. Patients who were admitted for the administration of chemotherapy are identified using ICD- 10 codes. The epidemiology, the role of insurance providers in the treatment outcome were studied. Results: A total of 29,018 hospitalizations for the administration of chemotherapy were there in 2017. The median age of patients who received chemotherapy was 48. The overall mortality related to chemotherapy admissions was 0.80% (n = 233). The mortality of females who were admitted for chemotherapy did not vary much when compared to males admitted for chemotherapy (0.89% vs 0.73%, p = 0.132). It was found that admissions for chemotherapy during weekend had 85 % higher odds of dying as compared to admission during weekdays (1.6% vs 0.76%, OR = 1.85, p = 0.001, CI = 1.16 – 2.95). Patients who were admitted electively for chemotherapy were 74% less likely to die in hospital when compared to those who were admitted emergently for chemotherapy (1.4 % vs 0.49% OR = 0.36, p = 0.001, CI = 0.266 – 0.49). Interestingly, patients who had Medicare and Medicaid had higher mortality than those who had private insurance and self-pay when admitted for chemotherapy (2.08 % vs 0.58% vs 0.36%, p = 0.00). Those who had private insurance were 60% less likely to die in hospital while admitted for chemotherapy. The average length of stay for chemotherapy admissions were 5.92 ± 7.9%. Conclusions: Medicare and Medicaid patients, weekend admissions and emergent admissions were more likely to die in hospital while admitted for chemotherapy. Further studies are needed to reveal the disparities in the mortality of chemotherapy admissions, based on the socioeconomic status and the insurance payers.
Biological correlates to support a clinical role for tagraxofusp, a novel targeted therapy directed to CD123, in combination with pomalidomide and dexamethasone, to target plasmacytoid dendritic cells in poor-risk patients with multiple myeloma.
Authors: Dharminder Chauhan, Arghya Ray, Yan Song, Arturo Olguin, Janice Chen, Christopher Brooks, Tariq I. Mughal, Paul G. Richardson, Kenneth Carl Anderson
Journal: Journal of Clinical Oncology (2020)

e20537 Background: We have previously described the pivotal pathogenetic role of plasmacytoid dendritic cells (pDCs; CD123/IL-3Ra + ) in multiple myeloma (MM) (Chauhan et al Cancer Cell, 2009,16:309). In preclinical MM models, we demonstrated that tagraxofusp, a novel targeted therapy directed to CD123, triggers anti-MM activity by reducing the viability of MM-promoting pDCs. These observations led to an ongoing phase 1/2 clinical trial of tagraxofusp in MM patients (NCT02661022). The treatment regimen demonstrated safety and efficacy, with 5 of 9 heavily pretreated patients achieving durable partial response (PR). Here, we report the initial results of our translational exploratory studies using bone marrow (BM), peripheral blood (PB), and serum from the study cohort. Methods: pDCs and MM tumor cells were purified from BM/PB samples and quantified using FACS, as described ( Ray et al Leukemia, 2018,32:843). A high-throughput seroproteomics platform SOMAscan was utilized to analyze 1,310 protein analytes in serum samples from MM patients (N = 9). SOMAscan data were subjected to meta-analysis to generate heatmaps, followed by hierarchical cluster analysis. SOMAscan results were validated with ELISA using supernatants from MM patient pDCs cultured with or without tagraxofusp. Results: Analysis of BM/PB samples from MM patients receiving tagraxofusp therapy showed a marked reduction in the frequency of viable pDCs [average 2% at screen vs 0.75% post-tagraxofusp; N = 6; p = 0.036]. pDCs isolated from tagraxofusp-treated patients showed decreased ability to trigger MM cell growth. Seroproteomics analysis of MM patient serum before and after tagraxofusp therapy showed alterations in the levels of 100 proteins [Median Fold Change in expression: 0.39 to 4.5; n = 6; 3 each; p &lt; 0.05]. Importantly, we found that tagraxofusp treatment reduced pDC-related soluble proteins, in particular, IFN-a and IL-3Rα. Additionally, our earlier study showed that pDC-MM interactions triggered secretion of MM cell growth including IL-3, which serves a dual role of promoting pDC survival and MM cell growth. Importantly, tagraxofusp decreased serum IL-3, suggesting that tagraxofusp attenuates survival mechanisms for tumor-promoting pDCs. Conclusions: Our current correlative studies validate target specificity of tagraxofusp and support further evaluation for this novel therapeutic to improve the clinical outcome of patients with MM.
Germline mutations in Brazilian pancreatic carcinoma patients.
Authors: Livia Munhoz Rodrigues, Simone Maistro, Maria Lucia Hirata Katayama, Luiz A.Senna Leite, Joao Glasberg, Ulysses Ribeiro, Rodrigo Santa Cruz Guindalini, Maria A. A. Koike Folgueira
Journal: Journal of Clinical Oncology (2020)

e16749 Background: Pancreatic cancer has the prospect of becoming the second leading cause of cancer death by 2030. The NCCN Guidelines recommend genetic testing for all patients with pancreatic cancer, however, the spectrum of germline mutations has not been extensively evaluated because recent studies with genetic testing have explored only a limited number of genes and have focused predominantly on Caucasian populations. Therefore, our objective is to evaluate the frequency and spectrum of germline mutations in unselected patients with pancreatic cancer in a multiethnic population. Methods: Patients from Instituto do Câncer do Estado de São Paulo (Brazil) with histopathological diagnosis of non-endocrine pancreatic carcinoma were included, regardless of the family history of cancer. These patients answered a life habits and family history of cancer questionnaire and supplied blood for the Next Generation Sequencing (MiSeq platform) with the TruSight Hereditary Cancer panel (Illumina), which includes 115 cancer predisposing genes. Variant analysis was performed with the VarStation, a Brazilian tool that offers post-sequencing computational support and aid for clinical interpretation. Results: To the present moment, 77 patients were evaluated. The mean age of the patients was 62 years (27-83), among whom, 13% with young age (≤50 years) and 47 women (61%). Thirty-eight patients (49%) reported cases of cancer in first-degree relatives. Regarding risk factors, 41 patients (53%) reported smoking, 19 (25%) alcohol ingestion and 20 (26%) had obesity. Seven out of 77 patients presented pathogenic variants in ATM (n = 2) , CHEK2, FANCM (n = 2) or PALB2 (n = 2) genes. Two of these patients ( CHEK2 and FANCM) had early onset pancreatic cancer (≤45 years), both denied smoking habit and family history of cancer in 1st degree relatives. Two patients, who were ATM mutation carriers, reported 1 st or 2 nd degree relatives with cancer and are alive after 4 and 8 years of diagnosis. Conclusions: In this unselected group of pancreatic cancer patients, 15% were young, almost half reported first-degree relatives with cancer and 9% were carriers of pathogenic variants in genes related with the homologous recombination DNA repair.
Serum amyloid A protein in identification of disease activity and infection for systemic-onset juvenile idiopathic arthritis
Authors: Fangfang Shen, Haiyan Xue, Lanfang Cao
Journal: BMJ (2019)

We retrospectively analyzed 126 children with juvenile idiopathic arthritis (JIA) admitted from January to December 2017, including 65 cases of systemic-onset JIA (SoJIA) and 61 cases of other types of JIA. The value of serum amyloid A protein (SAA) in the identification of the disease activity and infection in children with SoJIA was assessed. The area under the ROC curve of SAA in identification of disease activation of SoJIA patients was 0.934, which was not significantly different with other types of JIA. With the cut-off value of 68.32 mg/L the sensitivity and specificity for diagnosis of SoJIA activity were 0.913 and 0.892 respectively. In SoJIA patients the SAA was closely correlated with ESR and CRP (r=0.721 and 0.699, P<0.001). The SAA level was significantly higher in the disease active stage than that in stable stage, in the stable stage with infection than that in the stable stage without infection of SoJIA patients. There were also significant differences in platelet and CRP between active disease with infection and active disease without infection. SAA is expected to be used for assessing disease activity of SoJIA, if combined with platelet and CRP, it may be of value in the identification of the complicating infection.


Key words: 
Serum amyloid A protein; Juvenile idiopathic arthritis; Disease activity; Infection
Nivolumab for thymic epithelial tumors: Case series.
Authors: Adnan Aydiner, Naziye Ak
Journal: Journal of Clinical Oncology (2020)

e21115 Background: Metastatic and unresectable thymoma (T) or Thymic Carcinoma (TC) have limited treatment options, especially after first line. Methods: Patients with unresectable or recurrent thymic tumors who used minimum one dose of Nivolumab at any line of treatment were evaluated retrospectively. Even though standart dose of nivolumab is 3mg/kg dosage, due to financial concerns we used low dose regimen mostly. Results: 8 patients with TC (n = 3), T (n = 4) and mixt histology (n = 1) were included to study. Patients used nivolumab between April 2018 and August 2019, as median 3 rd line of treatment. One patient used as first line treatment due to chemoresistant disease at neoadjuvant line. Three patients had previous myasthenia gravis that had to be controlled before treatment. Four patients showed moderate (n = 2) or severe (n = 2) adverse events with nivolumab treatment. Interestingly, two severe adverse events were occurred at first dose even with 40 mg nivolumab and required cessation of treatment permanently. Median follow-up time was 16.1 months (range: 12.7-165.4). The median number of nivolumab received was four (range: 1 – 18). Best response was partial response. Two patients progressed at the 3rd and 5th month of treatment. One of the patients with inoperable disease initially underwent surgery after nivolumab therapy. Duration of response for one patient with TC and one patient with T B2 were 9 and 14 months, respectively. Median survival time after nivolumab was 7.4 months (range: 2-22.1). Conclusions: Despite the small number of patients, nivolumab is an option for T and TC patients. Low dose nivolumab may also be very toxic for T, especially in patients with known myasthenia gravis history. [Table: see text]
国内外患者满意度测评工具及其特点
Authors: 李慧, 顾杰, 祝墡珠, 江孙芳
Journal: BMJ (2012)

随着生物医学模式向生物-心理-社会医学模式的转变,医疗服务观念由以治疗为中心向以患者为中心转变,医疗服务机构越来越重视患者的感受,患者满意度调查受到越来越多医院和上级主管部门的重视.目前国内无公认统一的患者满意度评价方法,这就为临床开展调查造成了困难.本文试对国内外患者满意度的评价方法进行总结,便于研究人员选择和使用。
睡眠呼吸暂停与心血管疾病专家共识
Authors: 睡眠呼吸暂停与心血管疾病专家共识写作组
Journal: BMJ (2010)

一、概述 睡眠呼吸暂停(sleep apnea,SA)的主要特点是睡眠过程中由于上气道完全或部分阻塞和(或)呼吸中枢驱动降低导致呼吸暂停,从而产生慢性间歇性低氧、二氧化碳潴留、反复胸腔内负压增大、反复微觉醒、睡眠结构异常、白天嗜睡及记忆力下降,并可引起自主神经功能紊乱等。