tbuckley/cabot-search huggingface dataset:
Impact of failure to thrive on inpatient mortality and resource utilization in patients with head and neck cancer: A nationwide analysis.
Authors: Binav Baral, Prasanth Lingamaneni, Fred R. Rosen, Trilok Shrivastava, Krishna Rekha Moturi, Ishaan Vohra, Muhammad Zain Farooq
Journal: Journal of Clinical Oncology (2020)

e18531 Background: Failure to thrive (FTT), encompassing malnutrition and cachexia, is a common comorbidity afflicting Head and Neck cancer (HNC), brought about either by progression of disease or complications of treatment. FTT can exacerbate infections or cytopenias and delay wound healing, and has shown to affect survival in HNC. This study aims to explore the effects of FTT on mortality and resource utilization among hospitalized patients with HNC. Methods: Adult patients with HNC admitted from 2012-2017 were identified from the Nationwide Inpatient Sample database. Temporal trends of resource utilization across six years were evaluated. Multivariable logistic regression was used to evaluate risk factors for malnutrition and mortality in patients with HNC. Results: A total of 448,255 patients met inclusion criteria, of which 27.2% had FTT. Mean age was 66.3 years. Patients were predominantly male (71.8%) and white (70.4%). Patients with FTT had higher mortality (6.3% vs. 3.6%, p&lt;0.0001), longer hospital stay (9.1 vs. 5.7 days, p&lt;0.0001) and higher hospital charges ($23k vs. $18k, p&lt;0.0001). On multivariate analysis, risk factors for FTT included male sex, African American (AA) race and higher comorbidity burden. After adjusting for confounders, patients with FTT had higher inpatient mortality (OR 1.71, 95% CI 1.60-1.83, p&lt;0.001). There is an increasing trend of FTT in HNC over the years, from 22.7% to 32.6% (p trend &lt;0.001). Temporal trends in mortality, length of stay and hospital charges in those with FTT did not change significantly. Conclusions: Patients with HNC and FTT had higher inpatient mortality than those without FTT. AA patients especially were at higher risk of FTT. Inpatients with HNC and FTT had longer mean hospital stay by 3 days incurring higher healthcare costs. The study highlights an under acknowledged paradigm in HNC care and warrants further steps towards more vigilant nutritional surveillance and interventions, such as early/prophylactic enteral feeding in HNC patients. This could greatly improve quality of life and objective outcomes in HNC patients. [Table: see text]
Aldehyde dehydrogenase 3a2 protects AML cells from oxidative death and the synthetic lethality of ferroptosis inducers
Authors: Rushdia Zareen Yusuf, Borja Saez, Azeem Sharda, Nick van Gastel, Vionnie W. C. Yu, Ninib Baryawno, Elizabeth W. Scadden, Sanket Acharya, Shrikanta Chattophadhyay, Cherrie Huang, Vasanthi Viswanathan, Dana S'aulis, Julien Cobert, David B. Sykes, Mark A. Keibler, Sudeshna Das, John N. Hutchinson, Michael Churchill, Siddhartha Mukherjee, Dongjun Lee, Francois Mercier, John Doench, Lars Bullinger, David J. Logan, Stuart Schreiber, Gregory Stephanopoulos, William B. Rizzo, David T. Scadden
Journal: Blood (2020)
Lung cancer exosome specific protein 1(LESP-1) as a potential factor for diagnosis and treatment of non-small cell lung cancer.
Authors: Hyun Koo Kim, Hyesun Jeong, Byeong Hyeon Choi, Yu Hua Quan, Jiyun Rho, Ji-Ho Park, Yong Park, Yeonho Choi, Kook Nam Han, Young Ho Choi, Sunghoi Hong
Journal: Journal of Clinical Oncology (2020)

e15550 Background: Exosomes are endosome-derived nano size (30-150 nm) extracellular microvesicles released from many cell types including cancer cells and encapsulated by cell membrane play a key role for cell to cell communication. Use of exosomes as a biomarkers in lung cancer is a rising nanotechnology in a liquid biopsy. We explored a role of an exosome specific marker and the relationship between pathological stage of lung cancer patients who underwent surgery and lung cancer specific exosome markers. Methods: Conditioned medium from non-small cell lung cancer (NSCLC) cells and human pulmonary alveolar endothelial cell (HPAEpiC) was collected and exosomes were isolated by size exclusion chromatography. Proteomics analysis was performed to investigate lung cancer specific proteins. Written informed consent was obtained from all human subjects (17 controls and 54 patients), approved by the Korea University Guro Hospital Institutional Review Bored. Plasma exosomes were isolated using dual size exclusion chromatography. We validated proteomics results with lung cancer exosome-specific protein 1 (LESP-1) ELISA assay and western blot assay in lung cancer patients with healthy control. Cancer cell lines with pCMV-CD63-GFP were transduced by lentiviral vectors containing LESP-1 shRNA. The distribution of GFP+ exosomes and cell migration were examined by immunocytochemistry (ICC) and cell migration assay. Results: We identified LESP1 by the proteomics analysis of exosomes from NSCLC cell lines, but not in HPAEpiC cell. Level of LESP1 was dramatically increased in exosomes from NSCLC cell lines and from NSCLC patients. LESP-1 concentration increased in lung cancer patients than healthy controls ( p &lt; 0.0001) and increased according to the grade of lung cancer stage in peripheral blood ( p &lt; 0.0001). Western blot results confirmed the presence of the LESP1 with higher intensity band at each grade of lung cancer stage than healthy controls. Interestingly, we found that the number of GFP+ exosomes was decreased and cell migration was inhibited when the LESP1 was suppressed in NSCLC cells. Conclusions: The LESP-1 in exosomes was highly expressed in blood plasma of lung cancer patients, and the exosome release and cancer cell migration was inhibited by the LESP-1, which suggest that LESP-1 could be a feasible factor for diagnosis and treatment of non-small cell lung cancer.
Abstract 16570: Interleukin-10 Deficiency Impairs Reparative Properties of Bone Marrow-Derived Endothelial Progenitor Cell Exosomes
Authors: Yujia Yue, Venkata N Garikipati, Suresh K Verma, David A Goukassian, Raj Kishore
Journal: Circulation (2017)

Endothelial progenitor cell (EPC)-based therapy has immense potential to promote cardiac neovascularization and attenuate ischemic injury. Functional benefits of EPCs and other adult stem cell ther...
Application of SF-36 in studying their cognitive function and quality of life in the elderly of community
Authors: 李春波, 张明园, 何燕玲, 吴文源, 吴莹, 陈爱保, 徐明颖
Journal: BMJ (2004)

目的 探索社区不同认知功能状况老年人群的生命质量及其相关因素.方法采用截断面调查,以社区65岁以上人口构成为基准,按居民里委为单位进行整群随机抽样.应用上海市社区老年人群健康问卷VER2000(包括健康状况调查问卷和简易智能状态检查等);按照认知功能、日常生活能力、目前心境和有无躯体残疾4个维度分成3个等级的健康状况水平,共计1 455名纳入分析,采用单因素及多因素等统计方法完成有关分析.结果在控制年龄、教育程度和性别因素后,3组健康状况调查问卷(SF-36)的8个因子分仍具有显著性差异.简易智能状态检查总分与躯体功能、躯体健康所致角色限制、躯体疼痛、总体健康感、生命活力、社交功能、情绪问题所致角色限制和精神健康分量表的偏相关系数分别是0.31、0.12、0.16、0.23、0.25、0.32、0.14、0.11,具有显著性相关.结论本研究提供了社区老年人群生命质量的基线数据;发现社区老人认知功能与生命质量密切相关,通过成功老龄化干预、提高认知功能水平有望提升老年人的生命质量。
大剂量甲泼尼龙联合丙种球蛋白治疗重症药疹13例
Authors: 冯佃芹, 杜萍, 刘秀珍
Journal: BMJ (2012)

对2006年1月至2010年10月收治的13例重症药疹患者的临床特征及诊治情况做回顾性分析,表明大剂量甲泼尼龙联合丙种球蛋白治疗重症药疹,临床症状缓解明显,眼部病变恢复迅速,后遗症状少而轻微,不良反应少。
HGCSG 1803: Single-arm phase II study evaluating efficacy of oxaliplatin, irinotecan and S-1 combination therapy (OX-IRIS) in metastatic pancreatic cancer as first-line treatment.
Authors: Shintaro Nakano, Yasuyuki Kawamoto, Satoshi Yuki, Kazuaki Harada, Susumu Sogabe, Masayoshi Dazai, Atsushi Sato, Atsushi Ishiguro, Michio Nakamura, Shinya Kajiura, Yasuo Takahashi, Hidenori Karasaki, Miki Tateyama, Kazuteru Hatanaka, Yasushi Tsuji, Takahide Sasaki, Yoshiaki Shindo, Tomoe Kobayashi, Yuh Sakata, Yoshito Komatsu
Journal: Journal of Clinical Oncology (2020)

TPS4668 Background: Combination chemotherapy with oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX) showed improved survival compared to gemcitabine monotherapy for patients with metastatic pancreatic cancer and has become the one of the standard regimens. Despite of its clinical benefit, FOLFIRNIOX needs continuous infusion of 5-FU for 46 hours, which impairs quality of life. In other gastrointestinal cancer, infuser pomp free regimens, in which oral 5-FU drug replace the continuous infusion of 5-FU, have developed as alternative regimen. Therefore, we planned to develop new combination chemotherapy with oxaliplatin, irinotecan and S-1 (OX-IRIS) for advanced pancreatic cancer. We previously conducted the phase Ⅰ study for assessing the safety and determining the recommended dose of OX-IRIS regimen. Methods: To evaluate efficacy and safety of OX-IRIS, HGCSG1803 study staeted as a multicenter, non-randomized, single arm, prospective, phase II study in December 2019. The patients with untreated metastatic or relapsed pancreatic cancer are eligible for this study. OX-IRIS is administered as follows; a 30-min intravenous infusion (IV) of antiemetic, a 2-h IV of oxaliplatin at 85 mg/m 2 , a 1.5-h IV of irinotecan at 150 mg/m 2 on day 1 and day 15 of each 4-week cycle, and S-1 (40 mg/m 2 ) was taken orally twice daily, from after dinner on day 1 to after breakfast on day 15, followed by a 14-day rest, and to be repeated every 2 weeks until disease progression, unacceptable toxicity, or patient refusal. The primary endpoint is response rate, and the secondary endpoints are overall survival, progression-free survival, safety, and dose intensity for each drug. A total of 40 cases are planned for registration from 18 institutions in Japan within 2.5 years. Clinical trial information: jRCTs011190008 .
Can a brief multimedia intervention facilitate breast cancer patients’ communication about sexual health? Findings from a randomized controlled trial.
Authors: Jennifer B. Reese, Mary Catherine Beach, Kristen A. Sorice, Whitney Pollard, Mary Beryl Daly, Elizabeth A. Handorf, Laura S Porter, James A. Tulsky, Stephen J Lepore
Journal: Journal of Clinical Oncology (2020)

e24179 Background: Many women with breast cancer (BC) lack the confidence to discuss sexual health with their clinicians. We evaluated, in a randomized controlled trial, a brief multimedia intervention designed to facilitate BC patients’ communication about sexual health. Methods: We randomly assigned BC patients to either a multimedia sexual/menopausal health communication skills intervention [ Starting the Conversation (STC), including a video, workbook, and pamphlet with local and web-based resources] or a control [resource guide only]. About 1-2 weeks after patients received materials, we audio recorded a clinic encounter with their BC provider, and subsequently coded the dialogue for patients raising the topic of sexual health or asking &gt; 1 sexual health question. Self-report surveys administered at baseline, post-intervention, and 2-month follow-up assessed patients’ self-efficacy for discussing sexual health with their BC providers, sexual function, anxiety and depression, and quality of life. T-tests or mixed-effects logistic regression compared study arms; analyses of communication outcomes (patient raising the topic or asking a question during clinic encounter) were clustered by providers. Results: Study participants were 144 BC outpatients (82% acceptance rate; mean age = 56; 67% white; 15% metastatic; 31% active treatment). Women in the STC arm versus the control arm were more likely to raise the topic of sexual health [OR = 2.48 (1.11, 5.55), p= .03] and more likely to ask a sexual health question [OR = 2.93 (1.04, 8.26), p= .04]. Specifically, 51% of women in the STC arm raised the topic of sexual health versus 30% in the control arm and 40% of women in the STC arm asked a sexual health question versus 19% in the control arm. At 2-month follow-up, women in the STC arm showed greater improvements in self-efficacy ( p= .03) and anxiety, t(139) = 2.0, p= .04) compared to the control arm. Conclusions: STC, a brief multimedia intervention, was effective in facilitating BC patients’ communication about sexual health during routine clinic encounters and significantly reduced patients’ anxiety, possibly due to greater patient confidence in expressing their medical needs. Future studies should use longer-term follow-up and examine how sexual health communication can translate to improved patient sexual outcomes. Clinical trial information: NCT03624972 .
Phase II study of mitomycin-C and cisplatin in heavily pretreated advanced breast cancer
Authors: X. Hu, H. Guo, X. Yang, X. Zhao, Y. Cai, Z. Wang, S. Leaw, J. Li
Journal: Journal of Clinical Oncology (2006)

10713 Background: There were no standard chemotherapy regimen to patients with advanced breast cancer who had been exposed to anthracyclines, vinorelbine and taxanes. The mitomycin-C and cisplatin combination was investigated in this subgroup of patients. Methods: Three-weekly regimen consisted of mitomycin, 6 mg/m 2 administered intravenously on day 1, and cisplatin, 25 mg/m 2 intravenously on day 1–3. Results: 38 patients aged 25–75 years (median: 46 years) were treated with an overall response rate of 31.6%. The median time to progression (TTP) was 4.0 months. Median TTP for 12 patients with a complete or partial response was 9.0 months, while stable disease and progression of disease 4.0 months, p = 0.002. Grade 3/4 side effects of neutropenia, thrombocytopenia and nausea/vomiting were documented in 4 (10.5%), 4 (10.5%) and 3 (7.9%) patients, respectively. The median overall survival was 13+ months. Conclusions: The mitomycin-C/cisplatin doublet showed antitumor activity for anthracycline-, vinorelbine-, and taxane-resistant breast cancer comparable to other regimens. This well-tolerated regimen provides an affordable option for patients in China. No significant financial relationships to disclose.
乳腺X线立体钢丝定位术对不可触及乳腺病变的诊断价值
Authors: 曹旭晨, 杨建梅, 王庆全, 姚秉瑜, 宁连胜, 鲍润贤
Journal: BMJ (2006)

为了评价乳腺X线立体钢丝定位术对不可触及乳腺病变的诊断价值,应用美国ContourⅡ型175 mA高频钼靶乳腺X线机及立体定位系统,将乳腺定位针穿入可疑病变区,指导外科活检,并进行病理组织学检查.结果显示乳腺癌17例,囊性增生病10例,腺纤维瘤15例,导管上皮增生8例,腺病9例,导管内乳头状瘤3例,慢性炎症2例,脂肪瘤、囊肿各1例.提示X线立体钢丝定位术适用于不可触及乳腺病变的定位诊断,可提高乳腺癌早期检出率。
Mutation profile of colon cancer in hispanic population of central California.
Authors: Sanjay Hinduja, Mir Ali, Mohammed SANI Bukari, Uzair Bashir Chaudhary, Tanner Mortenson, Omar Mahmood, Matthew Lee, Fihr Chaudhary
Journal: Journal of Clinical Oncology (2020)

e16067 Background: The clinical and mutational profile of Hispanic patients with metastatic colon cancer is not well documented. In this retrospective study, we aim to describe the clinical and mutational profile of Hispanic patients with metastatic colon cancer in central California. Methods: We retrospectively evaluated the clinical and mutational profile of colon cancer at a single institution in Fresno, California from 2010-2019. We selected 136 patients out of which 70 patients self-identified as Hispanic and 66 self-identified as non-Hispanic. We studied clinical parameters and next-generation sequencing via Foundation one testing for these patients. Results: Among Hispanics, there were 43(61%) males and 27(38%) females. The median age at diagnosis was similar in both groups at 57. Right sided colon cancer accounted for 52% of Hispanic patients versus 40% in non-Hispanics. Fifty two percent of Hispanic patients presented with metastatic disease versus 45% in non-Hispanics. The frequency of commonly mutated genes in colon cancer in Hispanics versus non-Hispanics are as follows. KRAS (35.7% vs 37%), NRAS (11% vs 4%) BRAF (8% vs 7%), Her2/neu 0% in both groups. The frequency of other mutations such as TP53, APC, ATM, PTEN, CDKN2A, Myc amplification were also noted to be similar in both groups. PIK3CA mutation was seen in 18.6% of Hispanic patients versus 34% in non-Hispanic population which was statistically significant with a p value = 0.032. Microsatellite instability (MSI) was seen at 3.3% in Hispanics versus 10.6% in non-Hispanics. Tumor mutational burden was similar in both groups. Conclusions: The frequency of actionable mutations was similar in both Hispanic and non-Hispanic patients. Hispanics were noted to have lower PIK3CA and microsatellite instability. Metastatic disease and right sided colon cancer were seen at higher frequency in Hispanic population. Our results were similar to another population-based study which analyzed KRAS mutation with colon cancer patients in Puerto Rico[1]. Larger population based studies would be needed to further assess the differences in this patient population. Ruiz-Candelaria, Y., C. Miranda-Diaz, and R.F. Hunter-Mellado, K-RAS mutation profile in Puerto Rican patients with colorectal cancer: trends from April 2009 to January 2011. Int J Biol Markers, 2013. 28(4): p. e393-7.
Identifying biomarkers to guide immunotherapy treatment of cancer of unknown primary.
Authors: Linda R. Mileshkin, Atara Posner, Andrew Pattison, Shiva Balachander, Dariush Etemadmoghadam, Andrew Fellowes, Hui Li Wong, Eryn Dow, Anna deFazio, Bo Gao, Christos Stelios Karapetis, Madhu Sudan Singh, Ian M. Collins, Christopher Steer, Mark Andrew Warren, Narayan Karanth, David Bowtell, Owen W.J. Prall, Richard Tothill
Journal: Journal of Clinical Oncology (2020)

e15252 Background: Cancer of unknown primary (CUP) is a metastatic cancer where the primary tissue of origin (ToO) evades detection despite extensive clinical investigation. Recent approaches to the management of CUP have involved gene-expression profiling to resolve the likely ToO and mutational profiling to identify targeted treatments. Current evidence is that both of these methods can have some clinical benefit but only in a minority of cases. Immunotherapy may also be effective in CUP, but clinical trials looking at this are yet to report and the best way to select patients who may benefit is uncertain. Methods: Through a national cohort study called Solving Unknown Primary Cancer (SUPER), 245 CUP patients had molecular profiling performed and clinical follow-up. Variant detection from DNA sequencing using a targeted panel of 386 genes (SureSelect Agilent) was used to calculate tumour mutation burden (TMB). Additionally, a custom gene expression assay including 225 genes associated with ToO and 35 immune genes (SUPERDx, nCounter NanoString) was used to classify the likely ToO and immune profile the tumours. We used the genomic data from 217 of these patients to explore interdependencies between immune gene-expression patterns and TMB. We also retrospectively reviewed the outcomes of patients treated with anti-PD1/PD-L1 immune checkpoint inhibition (ICI) therapy in whom genomic data was available. Results: TMB was weakly correlated with a gene-expression score for immune response (IR) based on averaged z-score values of six genes (CD8A, IFNG, PRF1, PD-L1, GZMA, GZMB) (Spearman rho = 0.21) with many outliers exhibiting low TMB but high IR scores. Among twenty patients treated with ICIs, with both molecular data and response data available, 6 had a partial response (PR), 5 had stable disease (SD) and 9 had progressive disease (PD). We found that an elevated IR score was more predictive of ICI response than TMB. Most patients with either PR or SD to ICI treatment had a high IR score (9/10), and most patients with PD had low IR scores. However, only 3/10 patients with TMB available and a PR or SD had a high TMB ( &gt; 10). Conclusions: Our results demonstrate that ICI therapy may benefit some CUP patients and that an immune response gene-expression scoremay predict ICI treatment response.
Phase I study of tazemetostat, an enhancer of zeste homolog-2 inhibitor, in pediatric pts with relapsed/refractory integrase interactor 1-negative tumors.
Authors: Susan N. Chi, Franck Bourdeaut, Theodore Willis Laetsch, Maryam Fouladi, Margaret E Macy, Guy WJ Makin, Neerav Narendra Shukla, Cynthia Wetmore, Ashley S. Margol, Michela Casanova, Lindsay Baker Kilburn, Joanna Yi, Darren R. Hargrave, Geoffrey Brian McCowage, Navin R. Pinto, David Ebb, Giles W. Robinson, Laura Sierra, Melinda Merchant, Karsten Nysom
Journal: Journal of Clinical Oncology (2020)

10525 Background: Absence of integrase interactor 1 (INI1) expression is a defining molecular feature of rhabdoid tumors (RT), epithelioid sarcoma (ES), and chordomas, inducing dependence on enhancer of zeste homolog-2 (EZH2). Tazemetostat (TAZ) is a selective EZH2 inhibitor approved by the FDA for treatment of patients (pts) ≥16 yrs with metastatic or locally advanced ES ineligible for complete resection. Data from a Phase 1 (Ph1) pediatric dose-escalation study (Ph1a) of TAZ were previously reported; herein we report interim efficacy and safety from the Ph1 pediatric dose-expansion study (Ph1b). Methods: NCT02601937 is a Ph1, multicenter study in pts 6 months – 18 yrs evaluating TAZ administered BID at 1200 mg/m 2 in Ph1b, per Ph1a recommendation. Ph1b cohorts enrolled pts based on tumor type: Atypical teratoid RT (ATRT), RT, and other INI1-negative tumors (including ES and chordoma). The Ph1b primary endpoint was overall response rate (ORR). Secondary endpoints included safety/tolerability, duration of response (DOR), and survival. Results: Ph1b has enrolled 47 pts who received TAZ oral suspension. Across all tumor types, ORR was 17% (Table). Responses were observed in ATRT (4/21), chordoma (2/4), and ES (2/7); 1 pt dosed at 520mg/m 2 and 7pts at 1200mg/m 2 . In the ATRT cohort, 19% of pts responded to TAZ with a median DOR of 6.5 months. The median DOR has not yet been reached in the other cohorts, with ongoing responses in 3 pts. TAZ was generally well tolerated with no drug-related deaths. Most common adverse events (AE) include vomiting, nausea, and cough. During Ph1b enrollment, 1 pt with chordoma (dosed at TAZ 900 mg/m 2 for 15 months in Ph1a) developed a secondary malignancy (T-cell lymphoblastic lymphoma). In response, the pediatric recommended Ph2 dose was revised to limit exposure in pts without CNS involvement to 520 mg/m 2 TAZ (maximum dosing of 1 yr after response, pts to go off-treatment until disease progression). Conclusions: Interim results indicate TAZ is generally well tolerated in children with an AE profile similar to adults. Pt enrollment in the non-ATRT, INI1-negative cohorts is ongoing. TAZ shows promising anti-tumor activity in a subset of pediatric tumors, including ATRT, chordoma, and ES. Clinical trial information: NCT02601937. [Table: see text]
桥本甲状腺炎伴甲状腺激素抵抗综合征一例
Authors: 柳林, 孙丽萍, 逄力男
Journal: BMJ (2006)

患者女,49岁,农民.因乏力、厌食半年,加重伴声嘶3个月就诊.半年前无诱因出现乏力、食欲不振,大便次数少,约每周1次,无焦虑、烦躁多梦、怕热、多汗.3个月前出现颈部不适、声嘶,上述症状逐渐加重,时有胸闷、心慌.到我院普外科就诊,B超提示甲状腺肿大,可疑左侧甲状腺腺瘤;测游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)均显著升高,当时未测促甲状腺素(TSH).收住院行甲状腺腺瘤切除术,病理证实为淋巴细胞浸润性甲状腺炎.术后仍有声嘶,偶有饮水呛咳.出院后予丙基硫氧嘧啶50mg,2次/d;普奈洛尔(心得安)10 mg,2次/d.近1个月来出现眼干、面部浮肿、大便干燥,为进一步诊治收住内分泌科。