tbuckley/cabot-search huggingface dataset:
Effects of continuous positive airway pressure treatment on patients of obstructive sleep apnea syndrome accompanying with asthma
Authors: Li-jun Rui
Journal: BMJ (2010)

Objective To investigate effects of continuous positive airway pressure (CPAP)treatment on pulmonary function, frequency of asthmatic attack, and quality of life in patients of moderate to severe obstructive sleep apnea syndrome (OSAS) accompanying with asthma. Methods Twenty-three patients of OSAS accompanying with mild-to-moderate asthma were studied. They were divided into two groups, gastroesophageal reflux ( GER ) group ( n = 9 ) and non-GER group ( n = 14 ), based GER questionnaire score equal to or greater than 12, or less than 12. Pulmonary function tests (PFTs), Epworth sleepy score (ESS), quality of life for obstructive sleep apnea (QOLAp) score, quality of life for asthma (QOLAs) score and polysomnography (PSG) were measured for all the patients before and after four-week CPAP, respectively. Results No significant difference in PFTs was revealed before and after four-week CPAP between the two groups. However, there was significant difference in scores of QOLAp, ESS and QOLAs before and after four-week CPAP treatment, ( 12. 8 ± 2. 8 ) and (4. 6 ± 0. 9), ( 5. 1 ± 0. 7 ) and (6.3 ±0.6), and (4. 1 ±0.5) and (6.3 ±0.5) in GER group, and (13.0 ±2.9) and (4.6 ± 1.1),(4.7±0.5) and (5.6±0.6), and (3.6±0.3) and (5.8 ±0.6) in non-GER group, respectively (P＜0. 01 or 0. 05). Frequencies of asthmatic attack and nocturnal asthmatic attack reduced to ( 1.7 ± 1.1 )episodes per week and (0. 7 ± 0. 3) episodes per week after four-week treatment from (2. 9 ± 2. 0) episodes per week and ( 1.4 ± 0. 8) episodes per week before treatment ( P ＜ 0. 05 ) in GER group, but no significant difference was found before and after treatment in non-GER group. Scores of QOLAs increased more significantly in GER group than that in non-GER group ( P ＜ 0. 05 ). Conclusion CPAP treatment can significantly improve quality of life, rather than pulmonary function, in patients of OSAS accompanying with asthma, especially in those with GER symptoms.

Key words: 
Sleep apnea, obstructive;  Continuous positive airway pressure;  asthma;  Quality of life
XPO1-dependent nuclear export as a target for cancer therapy
Authors: Nancy G. Azizian, Yulin Li
Journal: Journal of Hematology & Oncology (2020)

Abstract Cellular homeostasis requires the proper nuclear-cytoplasmic partitioning of large molecules, which is often deregulated in cancer. XPO1 is an export receptor responsible for the nuclear-cytoplasmic transport of hundreds of proteins and multiple RNA species. XPO1 is frequently overexpressed and/or mutated in human cancers and functions as an oncogenic driver. Suppression of XPO1-mediated nuclear export, therefore, presents a unique therapeutic strategy. In this review, we summarize the physiological functions of XPO1 as well as the development of various XPO1 inhibitors and provide an update on the recent clinical trials of the SINE compounds. We also discuss potential future research directions on the molecular function of XPO1 and the clinical application of XPO1 inhibitors.
Nintedanib + docetaxel in lung adenocarcinoma patients (pts) following treatment with immune checkpoint inhibitors (ICIs): Updated efficacy and safety results of the ongoing non-interventional study (NIS) VARGADO (NCT02392455).
Authors: Christian Grohé, Wolfgang Blau, Wolfgang Gleiber, Siegfried Haas, Stefan Krüger, Harald Mueller-Huesmann, Mathias Schulze, Judith Atz, Rolf Kaiser
Journal: Journal of Clinical Oncology (2020)

9604 Background: Nintedanib (Vargatef) is an oral triple angiokinase inhibitor targeting VEGF-, PDGF- and FGF receptor pathways. It is approved in the EU and other countries in combination with docetaxel for treatment of locally advanced, metastatic or locally recurrent NSCLC of adenocarcinoma histology after 1st line chemotherapy. ICI +/- chemotherapy has changed the standard of care for 1st line treatment of metastatic non-mutated NSCLC. However, currently, only limited clinical data are available to help guide treatment decisions after prior ICI therapy in subsequent lines. Methods: This updated analysis is part of the ongoing NIS VARGADO (cohort B), a prospective non-interventional study of nintedanib + docetaxel after 1st line chemotherapy for adenocarcinoma NSCLC. The analysis includes 57 pts who had previously received both chemotherapy and ICI treatment. Results: Median age was 61 years (range: 45 – 80), 32/57 pts (56.1%) were men, and 41/57 pts (71.9%) were ECOG PS 0/1. 12/57 pts (21.1%) had brain metastases, and 46/57 pts (80.7 %) were current or former smokers. 1st line chemotherapy treatments included pemetrexed (36/57 pts, 63.2%), cisplatin (29/57 pts, 50.9%), carboplatin (33/57 pts, 57.9%), bevacizumab (14/57 pts, 24.6%), vinorelbine (13/57 pts, 22.8%), paclitaxel (8/57 pts, 14.0%), and docetaxel (1/57 pts, 1.8%). 2nd line treatments included nivolumab (34/57 pts, 59.7%), pembrolizumab (14/57 pts, 24.6%), and atezolizumab (7/57 pts, 12.3%). Under nintedanib and docetaxel, ORR was 50% (20/40 pts); DCR was 85.0% (34/40 pts). Median PFS was 6.5 months (95%CI 4.8 – 8.7), median OS was 12.4 months (95%CI 11.4 – 14.1). Treatment emergent adverse events (TEAEs) grade ≥3, serious TEAEs, and TEAEs leading to discontinuation were observed in 30/57 pts (52.6%), 30/57 pts (52.6%), and 17/57 pts (29.8%), respectively. Conclusions: This updated analysis of the VARGADO study continues to show the clinical benefit and manageable safety profile of nintedanib plus docetaxel in patients who had previously received both chemotherapy and ICI treatment. These data add to the real-world evidence that can inform clinical decision-making after prior ICI therapy. Clinical trial information: NCT02392455 .
Dyspnea as the main manifestation in somatic disorders and psychiatric disorders
Authors: Yuqing Song
Journal: BMJ (2017)

急性呼吸困难是常见的急诊患者就诊原因，重度呼吸困难是重症监护的原因之一。呼吸困难可以是精神心理疾病的症状，和焦虑、惊恐发作高度相关；也可以是躯体疾病伴随的焦虑表现，两者相互影响、恶性循环，积极的抗焦虑治疗可以缓解躯体疾病所致的呼吸困难。对呼吸困难的病因做出准确的诊断，防止误诊漏诊，采取有效的治疗措施，可缓解患者病痛，救助生命。
周围型肺癌的CT诊断
Authors: 马大庆
Journal: BMJ (2011)

周围型肺癌的基本影像表现为肺内的结节(直径≤3cm)和肿块(直径＞3 cm).在肺癌的综合影像诊断中,CT是主要的检查方法.多层螺旋CT的进展提高了≤3 cm肺癌检出和鉴别诊断的能力。
Exosomal microRNA in serum is a prognostic factor in cutaneous squamous cell carcinoma.
Authors: Jonggwon Choi
Journal: Journal of Clinical Oncology (2020)

e22073 Background: Functional microRNA(miRNAs) is located in the area of the gene related to cancer, such as inside of oncogenes and tumor suppressor genes, loss of heterozygocity or fragile site. There are many studies show that abnormal increase expression of miRNAs when cancer occurs. While some miRNAs commonly suppress abnormal expression of tumors, they can also infer the orgin of tumor tissues because they are more often representative of unique miRNA depending on type of tumor. In many case, the miRNAs expression patterns provide more characteristic information about tumors than messenger RNA expression profinling. The miRNAs expression patterns, which have changed with tumor types, provide clue that can serve as a biological markers for diagnosis, determining the outcome of disease, and predicting treatment responses. Indeed, several studies have reported thatextracellular miRNA is related to the prognosis of disease in some cancers, such as colon cancer and breast cancer. However, so far, there is no study that has been no defenitive study on how exosomal miRNAsare related to progrosis in cutaneous squamous cell carcinoma. We studied the association between the patient’s prognosis and miRNAs detected in cancer tissue and blood serum. Methods: We analyzed 35 patients who have various stage of cutaneous squamous cell carcinoma. Cancer tissue and serum samples were sequentially obtained. The miRNAs were prified from serum exosome and cancer tissues, and miRNAs sequencing was performed. The miRNAs expression profiles and copy number variations were observed using next generation sequencing (Hiseq, illumina inc) in 35 cancer tissues and serum samples. We validated miRNAs change and patient’s prognosis. Results: miR-142-5p cluster expression level in serum exosome and cancer tissue was most correlated with poor prognosis of cutaneous squamous cell carcinoma. Exosomal miR-142-5p expression level in serum were significantly higher(P &lt; 0.01) in patients with late stage than in patients with early stage. Also, the patients with recurrence showed high level of miR-142-5p. Conclusions: miR-142-5p expression level may be an important marker for predicting the patient’s prognosis and deciding whether undergo additional systemic chemotherapy after surgery.
Retrospective chart review to characterize admission to the ICU in the last 30 days of life and use of systemic anticancer therapy in the last two weeks of life at the Lifespan Cancer Institute.
Authors: Han You, Don S. Dizon, Nathan Wong, Edward W. Martin, Mary Anne Fenton
Journal: Journal of Clinical Oncology (2020)

e19202 Background: Admission to the ICU in the last 30 days of life and use of systemic anticancer therapy in the last 2 weeks of life are indicators of overly aggressive end-of-life care and have been incorporated into the American Society of Clinical Oncology (ASCO) Quality Oncology Practice Initiative (QOPI) as benchmarks to assess care across cancer centers. We sought to better define the proportion of patients at our institution who met either of these endpoints and to delineate factors that might be associated with them. Methods: A retrospective chart review was conducted on patients with solid tumors, who underwent anticancer therapy at the LCI, and died in timepoints ending in January, July and November of 2017. After IRB approval, patients were identified through our tumor registry. Patients’ electronic medical records were reviewed for past history, cancer stage, type of care received, palliative care contact, site of death, ICU admission in last 30 days of life, receipt of immunotherapy and biologic (precision) therapy in last 6 months of life, and systemic anticancer therapy (excluding antihormonal therapy) in last 2 weeks of life. Results: A total of 134 patients died in this time period; 18 were excluded (leukemia/myeloma) leading to 116 patients for this analysis. Our review showed that 16.4% of LCI patients were admitted to the ICU in the last 30 days of life and 9.5% received systemic anticancer therapy in the last 2 weeks of life. Significant factors associated with an ICU admission in the last 30 days of life were receipt of biologic (precision) therapy in the last 6 months of life (41.7% vs. 13.9%; P&lt;0.05) and never having been married (30.4% vs. 13.3%; P=0.05). Significant factors that were associated with death in the hospital were lack of palliative care team contact (34.3% vs. 13%; P&lt;0.05) and male gender (24.1% vs. 9.1%; P&lt;0.05). Conclusions: Understanding the factors associated with intensive care at the end of life is critical to the provision of value-based cancer care. In this study, the receipt of precision therapy in the last 6 months of life and never having been married were associated with ICU stays in the last 30 days of life, while lack of palliative care involvement and male gender were associated with greater chances of death in the hospital. Further understanding of the complex interplay that governs care and decision making in the end of life is required.
Predictive value of a CLIA-approved organoid based drug sensitivity test.
Authors: Astrid Margossian, Annie Richardson, Michael Churchill, Franz Schaub, Rachele Rosati, Lauren Appleyard, Madison Pollastro, Carolina Katabian, Kathleen Motamedi, Robert Diaz, Shalini Pereira, Christopher Kemp, Vijayakrishna K. Gadi, Carla Grandori
Journal: Journal of Clinical Oncology (2020)

3630 Background: Precision medicine integrates genetic, molecular, and clinical information to optimize therapy selection for cancer patients. Ex vivo drug testing has the potential to match the right drug to the right patient. We developed a CLIA-certified functional drug assay for all solid tumors which provides an actionable report of organoid sensitivity to targeted, endocrine and chemotherapy agents as a tool for therapeutic decisions. Objectives: To establish the predictive power of the test in relation to well-known genomic biomarkers as well as prior treatments to identify drug sensitivity. To demonstrate that functional drug testing increases the actionability of genomic reports. Methods: From 2016 to 2019, 240 organoids from cancer patients were subjected to functional testing at SEngine Precision Medicine. Patients with advanced primary or metastatic cancer (solid tumors) who were treatment naïve or had previous therapies fail. Fresh samples of tumor cells from core biopsies, surgical excisions, or fluids arrived &lt;48 hrs following collection and were cultured as 3D organoids. They were evaluated using a multi-dose response format with a library of up to 130 compounds. Drug sensitivity was quantified using a score that combines sensitivity and personalization of each patient’s response relative to a reference population. Known genomic actionability from levels of evidence 1-2 from MSKCC OncoKB were queried against results for correlation. Results: Organoids were derived from breast (18.7%), ovarian (18.3%), colorectal (17.9%), pancreatic (6.7%), and others solid tumors (38,3%). Median age of patients was 53 (r5-83). 68 drugs on average were tested per patient with a mean turnaround time of 18 days (r9 -37). A mean of 7 drugs per patient were identified as top scoring drugs. In 75 patients with genomic data, we found high concordance of drug sensitivity with known genomic anchors (e.g., inhibitors of BRCA1/ PARP, ERBB2/HER2, FGFR1-2/FGFR, KRAS, PIK3CA/PI3K), measured as sensitivity to drugs among this targeted groups. However, several patient samples demonstrated sensitivity to targeted agents in the absence of known genomic biomarkers. Most important, analysis of previous treatments indicated &gt;90% of retrospective concordance. Conclusions: Organoid based drug testing exhibits strong concordance with genomic and retrospective clinical evidence. In addition, functional testing identifies candidate therapies in patients with no known biomarkers and can identify the significance of variants currently not validated.
Neutrophil to lymphocyte ratio and lipi score prognostic value in patients with non-small cell lung cancer in a Mexican population.
Authors: Eduardo Reyes, José Fabián Martínez-Herrera, Raul Alejandro Andrade Moreno, Cesar Lara - Torres, Geovani Amador García, Alberto Villalobos Prieto, Alvaro Aguayo, Juan Alberto Serrano, Raquel Gerson, Guillermo Olivares
Journal: Journal of Clinical Oncology (2020)

e21593 Background: Non-Small cell lung cancer (NSCLC) is the most common type of lung cancer and accounts for most of all cancer-related morbidity and deaths in the World. Recent Evidence shows that inflammatory response is associated with a poor prognostic in several cancers. Evaluating these markers is of great importance to classify patients of solid tumors including NSCLC. Inflammatory markers like, Glasgow Prognostic Score (GPS), Lung Immune prognostic index (LIPI) and C-Reactive Protein (CRP) have been associated with poor prognosis in patients treated with immune checkpoint inhibitors. Neutrophil to Lymphocyte Ratio (NLR) is a biomarker for the general immune response to various stress stimuli in peripheral blood. It can be easily determined, inexpensive and can correlate with poor outcomes. Methods: A review of medical records was performed including patients from January 2013 to December 2018. The clinical characteristics were described, analyzed and the NLR and the LIPI were calculated. Categorical variables were analyzed with Chi-square test and the correlation was analyzed with the Pearson correlation coefficient. Variables were included in the construction of survival models through Cox multivariate regression using statistical software: STATA SE ver11.0 (StataCorp LLC Texas,USA). Results: A total of 175 patients with complete medical record and pathology samples were included. Around half of patients were female. The mean age was 69 years ± 11 years. The most frequent histology was Adenocarcinoma in 87%, Epidermoid 10% and others 3%. The most frequent mutations were KRAS 25%, EGFR 22% and ALK 1%. PDL-1 &gt; 1% was determined in 20% of patients. Clinical stage IV was found in 58% of the cases followed by Clinical Stage I, II and III with 25%, 9%, 8% respectively. The NLR &gt; 4 is associated with a worse prognosis in Stage I and II HR = 5.4 (95% CI 1.73 - 17.17, p = 0.004). LIPI &gt; 2 had predictive capacity for progression in Stage IV HR = 8.2 (IC 95 % 2.39-23.4, p = &lt; 0.001). Conclusions: NLR &gt; 4 showed prognostic value for recurrence in early clinical stages. LIPI score &gt; 2 resulted in higher risk for progression in metastatic stages. Determination of these indexes has the potential as a readily available prognostic indicator for patients.
Exploration of associations between adverse drug reactions and clinical outcomes in anlotinib treatment against medullary thyroid carcinoma (MTC): A subgroup analysis based on the ALTER01031 trial.
Authors: Yihebali Chi, Ming Gao, Pingzhang Tang, Xiangqian Zheng, Zhengang Xu, Dapeng Li, Xiaohong Chen, Minghua Ge, Yuan Zhang, Zhuming Guo, Jun Wang, Jie Chen, Jiewu Zhang, Ying Cheng, Zhendong Li, Hui Liu, Jianwu Qin, Jingqiang Zhu, Ruochuan Cheng
Journal: Journal of Clinical Oncology (2020)

e18518 Background: Anlotinib demonstrated favorable efficacy in a randomized, placebo-controlled phase 2b trial (ALTER01031, NCT02586350) for MTC which was published in 2019 ASCO annual meeting. Similar with other anti-angiogenesis drugs, hand-foot syndrome (HFS), hypertension and proteinuria were the major adverse drug reactions (ADRs) observed in this trial. We explored the association between common ADRs and the clinical outcomes with anlotinib in this subanalysis. Methods: Patients in the anlotinib group of ALTER01031 were divided into different groups according to the development of ADRs including HFS, hypertension or proteinuria. Kaplan-Meier method was used to estimate median PFS (mPFS) for patients in different groups. The mPFS for patients with or without dose reduction were also evaluated. Results: A total of 62 patients received anlotinib in ALTER 01031. HFS of any grade was observed in 39 patients with a mPFS of 28.5 months, which was longer than in those without HFS (14.0 months, P = 0.079). The hazard ratio for progression was 0.540 (95% CI 0.252, 1.158) although statistical difference was not reached. Similarly, more survival benefit was also observed in 29 and 38 patients who experienced hypertension and proteinuria, with mPFS of 28.5 months and 22.4 months respectively. While the mPFS for patients without corresponding ADRs were only 17.0 months (HR = 0.648 [95% CI 0.320, 1.314], P = 0.237) and 14.0 months (HR = 0.738 [95% CI 0.331, 1.65], P = 0.421). Median PFS had not been reached in 20 patients with dose reduction while was recorded as 17.0 months in those without (HR = 0.707 [95% CI 0.335, 1.496], P = 0.392). Conclusions: This analysis indicated a trend of greater PFS benefit for MTC patients treated with anlotinib who experienced HFS, hypertension or proteinuria although no statistical differences were observed. A possible positive association was also observed between dose reductions and better clinical outcomes. Clinical trial information: NCT02586350.
Clinicopathologic features and outcomes of de novo transformed indolent lymphoma.
Authors: Collin K Chin, Chan Cheah, Preetesh Jain, Nathan Hale Fowler, Luis Fayad, Jason Westin, Maria Alma Rodriguez, Mansoor Noorani, Sattva Swarup Neelapu, Fredrick B. Hagemeister, L Jeffrey Medeiros, Francisco Vega, Felipe Samaniego, Christopher Flowers, Loretta J. Nastoupil
Journal: Journal of Clinical Oncology (2020)

8061 Background: Untreated transformed indolent lymphoma (unTIL) can present as a composite lymphoma (COM), 2 or more separate sites of disease with one site transformed (discordant; DIS) or following indolent lymphoma sequentially (SEQ). Current practices are guided by small retrospective studies or extrapolated from trials involving non-transformed lymphomas. Methods: 353 patients (pts) with biopsy-proven unTIL treated with curative chemoimmunotherapy between 01/2000 to 01/2019 were included (intention to treat). All indolent B-cell lymphomas (iNHL) were included except CLL/SLL. Patients with MCL and non-DLBCL transformation were excluded. Prior therapy for iNHL was not allowed except one line of non-chemotherapy-based therapy. Kaplan-Meier method was used for time-to-event analysis including progression-free (PFS) and overall survival (OS). Results: 252 (71%) pts presented with COM, 50 (14%) DIS and 51 (14%) SEQ lymphoma. The underlying iNHL was: 308 (87%) follicular lymphoma, 37 (10%) nodal MZL, 7 (2%) MALT lymphoma, and 1 (0.3%) WM. Frontline therapy (FLT) included: RCHOP for 271 (77%), DAEPOCHR for 60 (17%), clinical trial for 7 (2%), BR for 4 (1%), RHCVAD for 2 (1%), RCEOP for 2 (1%), radiation therapy for 2 (1%), RFND for (1%) 2, RCVP for 2 (1%), and rituximab only for 1 (0.3%). 9 (3%) pts had ASCT in first remission. 50 (15%) pts received maintenance rituximab (MR) with fewer cases of HGBL-DH compared to the non-MR cohort (0% v 10%). With a median follow-up of 3.4 years (range 0.1-19.1), 4-year PFS and OS rates were 59% and 88%. By univariate analysis (UVA) the underlying type of iNHL, cell-of-origin and choice of induction therapy (DAEPOCHR v RCHOP) were not associated with inferior outcomes. SEQ transformations were associated with inferior OS on UVA (P = 0.02) which was not significant on multivariable analysis (MVA) (P = 0.3). MVA identified ECOG PS &gt; 1, B symptoms and HGBL-DH as independent prognostic factors for inferior PFS and OS. In patients who achieved PR or greater following FLT, MR was associated with improved PFS on MVA (HR 0.6, 95% CI 0.3-0.9, P = 0.04) without an OS benefit (P = 0.2). 39 (31%) pts relapsed with iNHL only (mPFS 2.4 yrs, 4-yr OS 94%) and 88 (69%) relapsed with transformed lymphoma (mPFS 1.1 yrs, 4-yr OS 69%) with no significant difference in pattern of relapse with MR (P = 0.2). Conclusions: The clinicopathologic features of unTIL are similar to those of de novo DLBCL. Escalation of therapy beyond R-CHOP may not be required in the absence of HGBL-DH. unTIL should be included in future clinical trials involving de novo DLBCL given the similar clinicopathologic features.