tbuckley/cabot-search huggingface dataset:
CA209-9JC: A phase II study of first-line nivolumab (NIVO) in patients (pts) with locally advanced or metastatic cutaneous squamous cell carcinoma.
Authors: Rodrigo Ramella Munhoz, Veridiana Pires De Camargo, Guilherme N Marta, Jade Cury Martins, Mirella Nardo, Caroline Chaul Barbosa, Carina Echer de Souza, Ingrid Barbosa, Herminia Ricci, Marcela Rodrigues de Mattos, Thiago Menezes, Guilherme Urano Machado, Eduardo Bertolli, Milton Jose Barros, Fabio A. Franke, Olavo Feher, Gilberto Castro
Journal: Journal of Clinical Oncology (2020)

10044 Background: Cutaneous squamous cell carcinoma (cSCC) is among the most frequent malignancies worldwide, and an increasing incidence has been documented over the past decades. For those not amenable to treatment with curative intent, immune checkpoint blockade (ICP) with anti-PD-1 monoclonal antibodies emerged as a novel therapeutic option, supported by evidences of high mutational burden and expression of PD-L1. In this single-arm study, we sought in investigate the activity of NIVO in pts with advanced cSCC (AcSCC). Methods: We conducted a Simon two-stage, open-label, phase II study to evaluate the safety/efficacy of NIVO for up to 24 systemic-treatment-naïve pts with metastatic and/or locaally advanced cSCC. NIVO at 3mg/kg was administered intravenously every 2 weeks (w) until disease progression, unacceptable toxicity or 12 months of treatment. The primary endpoint was the best objective response rate (bORR) at 24w as per RECIST criteria. Tumor measurements were performed every 12w. Secondary endpoints included safety/tolerability, progression-free survival (PFS) and overall survival (OS). Results: Between October 2018 and October 2019, 24 pts with AcSCC were enrolled, with a median age of 74 years (range 48-93) and a male/female ratio of 1.4:1. Most frequent primary sites were head/neck (42%), trunk (29%) and extremities (25%); identified risk factors included chronic sun exposure or burn scars in 66 % and 12.5 %, respectively. Upon enrolment, the proportions of patients with locally advanced, locoregional (regional lymph node involvement) and metastatic disease were 16.6%, 66.6% and 16.6%, respectively. At data cut off (median number of doses of NIVO: 15), 15 pts (62.5%) remain on treatment and 6 pts have progressed and/or died. Three pts completed 12 months of treatment and entered surveillance. Among 22 pts evaluable for response (n = 2 have not reached 12w of treatment), the bORR was 54.5% (12/22), and disease control (stable disease or objective response) was achieved in 77% (17/22). Median duration of response, PFS and OS have not been reached. Grade ≥3 treatment-related adverse events occurred in 21% of the pts, and 1 patient discontinued NIVO due to toxicities. Conclusions: NIVO resulted in robust antitumor activity and good tolerability in systemic treatment-naïve pts with AcSCC. There were no new safety signals, despite the inclusion of individuals at advanced ages. These data provide further evidence to support the use of ICP as the standard treatment option for pts with AcSCC. Clinical trial information: NCT03834233.
Community intervention in management of ankylosing spondylitis
Authors: Wen-guang Yu, Lu-yang Zhang, Rui-hua Dong
Journal: BMJ (2013)

Sixty five patients with of ankylosing spondylitis were randomly divided into intervention group (n=32) and control group (n=33). Patients in control group received conventional treatment only; in addition to conventional treatment, patients in intervention group also received community intervention, including health education, psychological counseling and joint function exercise. The treatment lasted for 6 months, 29 patients in intervention group and 28 in control group completed the trial. The results showed that the spinal motion (flexion, extension, lateral bending), chest expantion, finger to floor distance, occiput to wall gap in intervention group were better improved than those in control group after treatment (P<0.05). The scores of self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were lower in intervention group than those in control group after treatment (P<0.05). The results indicate that community intervention can effectively improve spinal mobility, reduce spinal deformity; relieve the anxiety and depression and improve the quality of life for patients with ankylosing spondylitis.


Key words: 
Ankylosing, spondylitis; Community health service
Prognostic value of dendritic cells in locally advanced cervical cancer patients.
Authors: Adrien Joseph, Maria Castedo-Delrieu, Norma Bloy, Nizar Labaied, Michele Mondini, Mauro Loi, Christophe Klein, Catherine Genestie, Patricia Pautier, Philippe Morice, Sebastien Gouy, Eric Deutsch, Cyrus Chargary, Guido Kroemer, Judith Michels
Journal: Journal of Clinical Oncology (2020)

e18016 Background: Cervical cancer is a Human papillomaviruses (HPV)-related disease. T cell infiltration is reported to be associated with a positive prognosis. We evaluated the prognostic value of the tumor-infiltrating dendritic cells (DC). Targeting this immune compartment might be clinically relevant. Methods: We characterized by immunohistochemistry the Dendritic cell lysosomal associated membrane glycoprotein (DC-Lamp) and CD8 T cell infiltration ( high/low according to the median density) in patients with locally advanced cervical cancer (LACC) undergoing curative-intent concurrent chemoradiation followed by uterovaginal brachytherapy boost. They were treated in our institution between March 2004 and August 2011. The image acquisition was performed with a Zeiss Axio Scan Z1 microscope. CD8 T cells were detected using an algorithm created in Visiopharm software on manually selected regions of interest (ROI) and DC-Lamp was detected manually. We exported the number of cells and the surface of ROI to calculate the density. Results: A total of 91 patients were identified, with a median follow-up of 4.2 years (range: 0.1-10.3). Patient’s characteristics are listed in the table. DC-Lamp high (n = 45) LACC patients showed a positive prognosis for overall survival (OS) by univariate (Odds Ratio (OR) = 0.20 [0.06 – 0.72], p = 0.013) and multivariate analyses (incorporating FIGO stage) (OR = 0.17 [0.05 – 0.61], p = 0.006). There was a positive correlation between DC-Lamp and CD8 (R = 0,25 et p = 0,095), which is significant in squamous cell carcinoma patients (R = 0.38, p = 0.039). There was a trend for improved risk stratification for the simultaneous assessment of DC-Lamp and CD8 levels, with DC-Lamp high /CD8 high patients having the best prognosis and DC-Lamp low /CD8 low patients having the worst prognosis (p = 0.074). Conclusions: LACC patients with high intratumoral DC density have a favorable outcome. These results underscore the clinical potential of therapeutic strategies that target DC (e.g. Toll like receptor agonists) to render more patients responsive to immune checkpoint blockers. [Table: see text]
During Aspergillus Infection, Monocyte-Derived DCs, Neutrophils, and Plasmacytoid DCs Enhance Innate Immune Defense through CXCR3-Dependent Crosstalk
Authors: Yahui Guo, Shinji Kasahara, Anupam Jhingran, Nicholas L. Tosini, Bing Zhai, Mariano A. Aufiero, Kathleen A.M. Mills, Mergim Gjonbalaj, Vanessa Espinosa, Amariliz Rivera, Andrew D. Luster, Tobias M. Hohl
Journal: Cell Host & Microbe (2020)
Identification of a stemness-related gene panel associated with BET inhibition in triple negative breast cancer.
Authors: Miriam Nuncia Cantarero, Leticia Serrano-Oviedo, Cristina Nieto Jiménez, David Tébar García, Miguel Burgos Lozano, Sara Morcillo García, Javier Perez Peña, Veronica Corrales-Sanchez, Balazs Gyorffy, Alberto Ocana, Eva María Galan-Moya
Journal: Journal of Clinical Oncology (2020)

e13098 Background: Triple negative breast cancers (TNBCs) are enriched in cells bearing stem-like features, i.e., cancer stem cells (CSCs), which underlie cancer progression. Thus, targeting stemness may be an interesting treatment approach. The epigenetic machinery is crucial for maintaining the stemness phenotype. Bromodomain and extra-terminal domain (BET) epigenetic reader family members are emerging as novel targets for cancer therapy, and have already shown preclinical effects in breast cancer. Here, we aimed to evaluate the effect of the BET inhibitor JQ1 on stemness in TNBC. Methods: Transcriptomic, functional annotation and qRT-PCR studies were performed on JQ1-exposed TNBC cells in culture. The results obtained were confirmed in spheroids and spheroid-derived tumours. In addition, limiting dilution, secondary and tertiary tumour sphere formation, matrigel invasion, immunofluorescence and flow cytometry assays were performed to evaluate the effect of JQ1 on CSC features. For clinical outcome analyses, the online tool Kaplan-Meier Plotter and an integrated response database were used. Results: We found that JQ1 modified the expression of stemness-related genes in two TNBC-derived cell lines, MDA-MB-231 and BT549. Among these changes, the CD44/CD24 ratio and ALDH1A1 expression level, i.e., both classical stemness markers, were found to be decreased by JQ1. Using a validated spheroid model to mimic the intrinsic characteristics of CSCs, we found that JQ1 decreased surface CD44 expression, inhibited self-renewal and invasion, and induced cell cycle arrest in G0/G1, thereby altering the stemness phenotype. We also found associations between four of the identified stemness genes, GJA1 , CD24, EPCAM and SOX9, and a worse TNBC patient outcome. The expression of another two of the stemness-related genes was found to be decreased by JQ1, ABCG2 and RUNX2, and predicted a low response to chemotherapy in TNBC patients, which supports a role for RUNX2 as a potential predictive marker for chemotherapy response in TNBC. Conclusions: We identified a stemness-related gene panel associated with JQ1 and describe how this inhibitor modifies the stemness landscape in TNBC. Therefore, we propose a novel role for JQ1 as a stemness-targeting drug. Loss of the stem cell phenotype via JQ1 treatment could lead to less aggressive and more chemo-sensitive tumours, reflecting a better patient prognosis. Thus, the identified gene panel may be of interest for the clinical management of patients with aggressive TNBC.
筛窦原发性结核一例
Authors: 张玉成
Journal: BMJ (2010)

患者男,36岁,工人.因前额部头痛伴发热1个月余于2007年12月20日以筛窦炎收入院.1个月前患者无明显诱因额部持续性闷痛,且伴有低热,无鼻塞、流涕及涕中带血,无盗汗、全身乏力等不适症状,否认结核病史及接触史.体格检查:体温37.7℃,脉搏86次/min,呼吸20次/min,血压110/75 mm Hg(1 mm Hg=0.133 kPa)。
Relativity between alexithymia and cognitive function in somatoform disorders
Authors: Feng Yi, Kai Zou
Journal: BMJ (2014)

To explore the relativity between alexithymia and cognitive function in somatoform disorder patients.A total of 40 patients aged 18-65 years fulfilling the criteria of ICD-10 for somatoform disorders were recruited as research group.And 40 normal healthy subjects were selected as control group.Toronto alexithymia scale-20 (TAS-20) was employed to examine the alexithymia.And cognitive abilities screening instrument (CASI) was used to measure their cognitive ability.The 9-factor scores and total score of CASI test in patients with somatoforill disorder were significantly lower than those in the normal controls (P<0.05 or <0.01). The 3-factor scores and total score of TAS-20 test in patients with somatoforill disorder were significantly higher than those in the normal controls (P<0.05 or <0.01). In research group, CASI scores were negatively correlated with the TAS-20 scores (P<0.05 or 0.01).


Key words: 
Somatoform disorders; Cognitive function
Pazopanib (PZ) plus endocrine therapy as treatment for hormone resistant advanced breast cancer (ABC).
Authors: Ozge Gumusay, Melanie Catherine Majure, Travis Deal, Jonathan R. Renslo, Chiara A. Wabl, Michelle E. Melisko, Amy Jo Chien, Andrei Goga, Mark Moasser, John Park, Jimmy Hwang, Hope S. Rugo
Journal: Journal of Clinical Oncology (2020)

1068 Background: A major limitation of endocrine therapy in hormone receptor positive (HR+) ABC is the development of resistance. Preclinical data suggests that higher levels of vascular endothelial growth factor (VEGF) are associated with endocrine therapy resistance. We conducted a phase II trial to evaluate the clinical benefit (CB) of PZ, a VEGF receptor tyrosine kinase inhibitor (TKI) combined with nonsteroidal aromatase inhibitors (NSAIs) in pts with ABC resistant to NSAIs. Methods: Eligibility included postmenopausal women with HR+ ABC and progressive disease (PD) after at least one month of NSAIs. Treatment was PZ 800 mg/day plus either letrozole or anastrozole. The primary endpoint was clinical benefit rate at 12 weeks (CBR12, wks). Secondary endpoints were PFS and safety. A CBR of 20% was considered a clinically meaningful comparison to the expected CBR of &lt; 5% with continued NSAIs after PD. Using a 2-stage design, stable disease in at least 1 of the first 13 pts allowed continued enrollment to a planned 28. Results: 32 pts were enrolled; 28 are evaluable for study endpoints and all patients completed the study. The median age was 58 years (range: 41-77). Pts were heavily pre-treated, with a median of 2 prior hormone therapies (range 1-6) and 1 prior chemotherapy (range 0-8). 8 pts (28.6%) stopped treatment due to adverse events (AE) including hypertension (HTN), fever, transaminitis, nausea, vomiting, rash, hand foot syndrome and pulmonary embolism (PE); 6 pts progressed before wk 12. CBR12 was 46.4% (12 SD, 1 PR); CBR24 was 25% (5 SD, 2 PR). Median PFS was 20 wks (95% CI 11-48, and median PFS for pts with CBR12 was 24 wks. 7 pts had PFS &gt; 6 months (24, 32, 36, 36, 48, 184 and 274 wks); 2 pts had PFS &gt; 3 years (184 and 274 weeks). The most common grade 1/2 AE were nausea (48.2%), fatigue (33.3%), diarrhea (29.6%), back pain (22.2%), and arthralgias (22.2%). Grade 3/4 AEs included HTN (3/28; 11.1), transaminitis (3/28; 11.1%), headache (2/28; 7.4), heart failure, vertigo, nausea, oral pain, vomiting, fever, fatigue, and hypokalemia (one patient each: 3.7%). Conclusions: The addition of PZ to NSAIs resulted in a CBR12 of 46.4%, and a CBR24 of 25% in pts with heavily pre-treated ABC resistant to NSAIs. These results support clinical efficacy of antiangiogenic TKI in HR+ ABC, and suggest benefit in hormone resistant disease. Expected toxicities resulted in early discontinuation in 28.6%, which limited drug exposure. Clinical trial information: NCT 01466972 .
脑卒中后抑郁的干预治疗对患者神经功能影响的观察
Authors: 吕秀东, 王艳玲, 王化刚, 刘立海, 王彦华, 刘风珍
Journal: BMJ (2005)

为观察脑卒中后抑郁的干预治疗对患者神经功能的影响,将80例脑卒中后抑郁患者分为治疗组和对照组各40例.两组患者入院第3天及治疗后第21天均进行美国国立卫生研究院卒中量表(NIHSS)、汉密顿抑郁量表(HRSD)和日常生活活动能力量表(ADL)评分,比较两组患者入院治疗3周后的评分情况.结果显示,治疗组NIHSS评分和HRSD评分明显减少,ADL评分明显增高;治疗后组间比较差异有统计学意义(P＜0.05).说明干预治疗能明显改善脑卒中后的抑郁状态,提高日常生活能力并促进神经功能的恢复。
Strategies of parenteral nutrition for premature infants
Authors: Ye Zhang, Yimei Ren, Yanyan Luo, Yue Li, Rong Ding, Xinxin Bu, Shudong Cui, Yuhua Hu
Journal: BMJ (2017)

Objective
To evaluate the appropriate strategies of parenteral nutrition for premature infants.


Methods
One hundred and seven preterm babies with birth weights ranging from 1 000-2 500 g received parenteral nutrition within 2 h after birth during June 2015 to January 2016.Lipids, glucose and electrolytes were applied with standard protocol of parenteral nutrition; while the amino acids contents were1.0-1.5 g·kg-1·d-1 in 81 cases (control group) and 2-2.5 g·kg-1·d-1 in 26 cases (study group). The data of demographics, development, laboratory findings and complications were documented.


Results
There were no significant differences in the baseline data of gestational age, birth weight between two groups (P>0.05). There were also no significant differences in total protein intake and target non-protein calorie intake within the first week after birth and the total calorie intake during the first two weeks between study group and control group (P>0.05). The start of enteral feeding [(3.54±3.18) d vs.(5.64±5.81) d, P=0.02)], the start of total enteral nutrition [(16.50±9.54) d vs. (21.21±15.63) d, P=0.07)], the recovery of birth weight [(7.35±4.55) vs. (9.19±9.50) d, P=0.19)] in study group were earlier than those in control group.The duration of parenteral nutrition [(16.88±8.99) d vs. (22.33±18.10) d, P=0.04], the duration of hospital stay [(20.62±10.41] d vs. (24.22±15.62) d, P=0.18] were shorter and the hospitalization expenses [(21 929.00 ±11 945.42] Yuan vs.(37 499.58±71 146.80) Yuan, P=0.14] were lower in study group than those in control group.The incidence of metabolic acidosis was significantly lower in study group than that in control group (19.23% vs. 45.68%, P=0.02). There were no significant differences in complications of necrotizing enterocolitis, sepsis, extrauterine growth retardation, parenteral nutrition-associated cholestasis, patent ductus arteriosus, respiratory distress syndrome, nosocomial and the duration of artificial ventilation and oxygen therapy between two groups (P>0.05). The incidence of metabolic disorders (hyperglycemia, hypoglycemia, hypocalcemia, hyponatremia, hypokalemia and hypomagnesemia) was similar in two groups (P>0.05).


Conclusion
Amino acids should be apply to the premature infants within 2 h after birth, and the contents in parenteral nutrition should be >2.0 g·kg-1·d-1.


Key words: 
Parenteral nutrition; Infant, premature; Amino acids
新しいプラチナ誘導体テトラクロロ(d,l‐トランス)1,2‐ジアミノシクロヘキサンプラチナ(IV)(テトラプラチン)の治療効果および薬理学的研究
Authors: Rahman A, Roh J K, Wolpert-Defilippes M K, Goldin A, Venditti J M, Woolley P
Journal: Cancer Research (1988)
Analysis on the community elder care in Bao'an district of Shenzhen
Authors: Shao-xian Chen
Journal: BMJ (2008)

The status of health care for elderly in 110 community health service (CHS) centers of Bao'an District was surveyed.Data were collected from directors,health care managers and health workers in CHS centers by questionnaire.The results showed that the establishment of health file was satisfactory.but the management of health file needed to be strengthened,particularly for those required special care.The nutritional and psychological counseling should be specially focused.
Communication about comorbidities among 527 older patients with advanced cancer and their oncologists and caregivers: A multisite cluster-randomized controlled trial.
Authors: Amber Kleckner, Nikesha Gilmore, Elizabeth Belcher, Allison Magnuson, Richard Francis Dunne, Ian Kleckner, Huiwen Xu, Eva Culakova, Megan Wells, Nicholas J. Vogelzang, Elie G. Dib, Valerie Targia, Luke Joseph Peppone, Karen Michelle Mustian, Supriya Gupta Mohile
Journal: Journal of Clinical Oncology (2020)

12040 Background: Older patients with advanced cancer often have comorbidities that increase the risk of toxicity from neoplastic therapy but are not always considered in treatment planning. We assessed the utility of a geriatric assessment (GA) intervention to increase the number and quality of discussions about comorbidities among oncologists, older patients, and caregivers. Methods: This multi-site trial enrolled patients who were ≥70 years, had advanced solid tumors or lymphoma, had ≥1 GA impairment, and who were considering or receiving cancer treatment. All patients received the GA and completed an Older Americans Resources and Services Comorbidity survey, which evaluated 15 conditions and interference with activities (clinical impairment = ≥3 comorbidities or ≥1 highly interfering). Oncology practices were randomized to intervention (GA with a summary with management recommendations provided to oncologists) or usual care (GA only). The clinic visit after GA was audio-recorded, transcribed, and coded for GA topics including comorbidity. Generalized linear mixed models adjusting for site (random effect) were used to assess the effect of the intervention. Results: Patients (n=527 evaluable, 76.6±5.2 years, 49% female) and oncologists (n=131, 63 in intervention) were enrolled from 31 sites. In total, 94.5% of patients had ≥1 comorbidity with an average of 3.2±1.9; 64% were clinically impaired by comorbidity (p=0.76 between arms). The intervention arm had twice the number of conversations about comorbidities (1.02 vs. 0.52 conversations per patient, difference 0.50, 95% CI 0.18-0.81, p=0.004) and conversations were more likely to be initiated by the oncologist (p&lt;0.001, Table). Moreover, among patients who had conversations about comorbidities, more patients in the intervention arm had discussions specifically addressing comorbidities (e.g., cancer treatment modification, communication with the primary care physician; 24.3% vs. 7.5%, p=0.003). Conclusions: Providing oncologists with a GA summary and recommendations encouraged them to engage in more discussions about their patients’ comorbidities with the goal of addressing interactions between comorbidities, cancer, and its treatments. Funds: PCORI CD4634, NCI UG1CA189961 Clinical trial information: NCT02107443 . [Table: see text]
Outcomes in minority patients (pt) with aggressive B cell lymphoma (BCL) if optimally managed with equal access to care and nurse navigation (NN).
Authors: Bei Hu, Tommy Chen, Danielle Boselli, Lisa Pye, Rupali Bose, Derek Raghavan, James Thomas Symanowski, Kris Blackley, Tamara Kay Moyo, Ryan Jacobs, Steven Park, Amy Soni, Belinda Avalos, Edward Alan Copelan, Nilanjan Ghosh
Journal: Journal of Clinical Oncology (2020)

e19040 Background: Aggressive BCL is curable but previous studies have shown that minorities have inferior survival, partly due to socioeconomic barriers and poor access to care. NN programs are designed to reduce barriers to care via various methods. We present disease characteristics, treatment, and outcomes of Caucasian (C) &amp; non-Caucasian (NC) pts with aggressive BCL at Levine Cancer Institute which has an active NN program. Methods: We collected demographic, insurance, disease characteristics, treatment, and outcomes for pts with aggressive BCL [diffuse large B cell lymphoma (DLBCL), primary mediastinal B cell lymphoma (PMBCL), or high grade B cell lymphoma (HGL)] between Jan 2016 and Jun 2019. Race (C or NC) was self-reported. NN encounters were characterized as low intensity (basic needs) or high (moderate/high needs). OS and PFS were calculated using Kaplan Meier. Demographics were compared using Fisher's Exact tests. Results: 204 pts (186 = DLBCL, 14 = PMBCL, 4 = HGL) were included (NC = 47; C = 157). NC were younger at diagnosis (median age 56 vs 62 yrs, p = 0.03) and more likely to be uninsured/Medicaid (26% vs 4%, p &lt; 0.0001). There were no significant differences in prognostic scores (44% vs 50% R-IPI score 3-5, p = 0.5), incidence of double hit (11% vs 13%, p = 0.8), frontline rituximab/anthracycline containing chemotherapy (98% vs 96%, p = 0.9), and incidence of relapsed/refractory (R/R) disease (40% vs 37%, p = 0.7) for NC compared to C. For R/R BCL, similar % of pts underwent hematopoietic stem cell transplant (SCT) (32% NC vs 28% C, p = 0.8) or CAR-T cell therapy (16% NC vs 19% C, p = 0.9). Enrollment in clinical trials was comparable (17% NC vs 14% C, p = 0.6). The % of pts receiving NN was similar (81% NC, 87% C, p = 0.4) but NC had higher intensity NN encounters (42% vs 21%, p = 0.01). With median follow up of 35 mo, OS and PFS were comparable between both groups. The 2 yr OS was 81% for NC and 76% for C, p = 0.3; 2 yr PFS was 62% for NC and 64% for C, p = 0.8. Conclusions: We show equivalent survival between Caucasian and non-Caucasian pts with aggressive BCL. Disease biology and treatment patterns--including access to SCT, CAR-T and clinical trials--were similar in both groups. Differences in insurance coverage favored Caucasians. Similar proportion of pts in both groups received nurse navigation, but non-Caucasian pts had higher intensity navigation needs. Providing equal access to care and availability of an active nurse navigation program may overcome racial heath disparities. This study has implications for national health policy.