tbuckley/cabot-search huggingface dataset:
Implementing a novel method to estimate the "Burden of Therapy" (BOTh) for patients with metastatic pancreatic cancer treated with gemcitabine plus afatinib vs. gemcitabine in the AIO ACCEPT trial.
Authors: Michael Haas, Ayad Abdul-Ahad, Robert Snijder, Dirk Thomas Waldschmidt, Michael Stahl, Anke C. Reinacher-Schick, Jens Freiberg-Richter, Florian Kaiser, Stephan Kanzler, Norbert Frickhofen, Thomas Seufferlein, Tobias Nicolaas Dechow, Rolf Mahlberg, Peter Malfertheiner, Gerald Illerhaus, Stefan Kubicka, Swantje Held, Stefan Hubert Boeck, Michael von Bergwelt-Baildon, Volker Heinemann
Journal: Journal of Clinical Oncology (2020)

e16786 Background: The phase II ACCEPT trial included 119 patients (pts) with histologically proven pancreatic cancer without any previous systemic treatment for metastatic disease. Pts were randomized in a 2:1 ratio to receive either afatinib 40mg orally once daily + gemcitabine (1000mg/m 2 iv weekly for three weeks followed by one week of rest, repeated every four weeks) or gemcitabine alone. The addition of afatinib did not lead to improved efficacy (7.3 vs. 7.4 months, HR 1.06, p = 0.80; data previously shown). The traditional analysis of adverse events was not able to reveal the actual patient´s burden in each of the treatment arms. Methods: BOTh is a highly sensitive, novel methodology utilizing patient-level data to derive a quantitative estimate for the “Burden of Therapy/Toxicity” (BOTh) that all or individual pts experience on each day of a clinical study * . The daily burden estimate is based on number and severity of adverse events (AEs) that occur contemporaneously and consecutively, in a combination of incidence and severity resulting in a major advantage over current methods. A chart displays the total burden experienced by pts on each day throughout the study and statistical analyses are performed with the area under curve. Results: The BOTh analysis revealed that the daily burden of toxicity for pts in the gemcitabine-alone arm was 6.8 compared to 11.5 in the combination treatment arm (p = 0.0005). However, the day to day variation in burden was higher in the gemcitabine-alone arm. The higher burden in the combination arm was already visible at a very early stage of the trial when most pts were still on treatment. Conclusions: Whereas the traditional analysis of AEs only gave a static interpretation, BOTh revealed a more dynamic view on burden of toxicity on pts taking single vs combination medication in a 200 day time frame. BOTh can facilitate better informed treatment selection. * Abdulahad A. et.al, Contemporary Clinical Trials Communications 4 (2016) 186-191. Funding: The ACCEPT trial was funded by an unrestricted financial grant by Boehringer Ingelheim. Clinical trial information: NCT01728818 .
The effect that β-lactam antibiotics have on progression free and overall survival in multiple myeloma patients undergoing autologous stem cell transplantation.
Authors: Marshall McKenna, Rena Feinman, Jaeil Ahn, Shuqi Wang, David H. Vesole, Stuart L. Goldberg, Giselle Alexandra Suero-Abreu, Miguel Gonzalez Velez, Jun Chih Wang, Abdul Rehman, Phyllis McKiernan, Michele Donato, Elli Gourna Paleoudis, David Samuel DiCapua Siegel, Noa Biran
Journal: Journal of Clinical Oncology (2020)

e20518 Background: Gut microbiome dysbiosis is correlated with graft-versus-host disease (GVHD) in allogeneic stem cell transplant (allo-SCT) patients. In the allo-SCT population, antibiotics have been associated with increased risk for GVHD mortality and relapse due to loss of gut obligate anaerobes . It has been shown that antibiotics may negatively impact the efficacy of checkpoint inhibitors for patients with solid tumors. Based on these studies, we performed a retrospective analysis to determine if antibiotic treatment affects outcomes of multiple myeloma (MM) patients after autologous SCT (ASCT). Methods: This is a single institution retrospective study at Hackensack University Medical Center. A list of consecutive MM patients treated from 1/2012 to 12/2015 was obtained and an electronic medical record review of the first 217 who received ASCT was performed. Baseline characteristics, treatment history, transplant course and antibiotic treatment (including β-lactams, fluoroquinolones, macrolides, metronidazole, and vancomycin) were reviewed. Prophylactic antibiotics were excluded. Response was defined using the IMWG criteria. Median progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Log rank tests were used to compare the difference in survival between stratified groups. The LASSO cox regression analysis method was used for multivariate analyses of PFS and OS. Results: Of the 217 patients, 205 patients were available for analysis. Median age at ASCT was 61. β-lactams were associated with decreased median PFS (1.95 vs 4.77 years (yrs), p &lt; 0.01) and decreased median OS (7.51 vs 13.45 yrs, p = 0.01). Multivariate analysis adjusting for lasso-selected age, gender, complete remission (CR) after ASCT, and ISS demonstrated independent progression risk associated with β-lactam use (HR = 2.00, 95% CI, 1.28–3.12, p &lt; 0.01). β-lactams were associated with worse OS in multivariate analysis adjusting for lasso-selected age, gender, CR after ASCT and high risk cytogenetics (HR = 1.89, 95% CI, 1.07–3.40, p = 0.03). Conclusions: In this preliminary study, β-lactams predicted for decreased PFS and OS compared to patients who did not receive β-lactams in MM patients undergoing ASCT. The study was limited by its retrospective nature but demonstrates one of the first evaluations of antibiotic effect on the ASCT population in MM. Prospective studies evaluating the impact of antimicrobials on patient outcomes and the gut microbiome are ongoing.
Perimenopausal clinical performance as well as cognition and demand for knowledge of perimenopause in community-dwelling women
Authors: Ling Shi, Huan-dong Lin, Hui Ma, Xiao-hua Shen, Li-ping Shen
Journal: BMJ (2013)

Objective
To explore the clinical performance and related factors of perimenopausal syndrome, cognition and demand for perimenopausal knowledge in community-dwelling women.


Methods
During June 2009 to December 2011, a cross-section survey of perimenopausal symptoms as well as cognition and demand for perimenopausal knowledge was conducted in 1546 women aged 45 to 65 years in Shanghai Changfeng Community.


Results
The average menopausal age of this population was (49.5±3.7) years. The total prevalence of perimenopausal syndrome was 75.7% (n=1094) and 81.4%, 76.5%, 65.4% in women with primary school, middle school and college education background respectively (P=0.007). Sexual disorders (80.8%), hot flushes & sweating (64.7%) and fatigue (55.8%) were the most common symptoms of perimenopause. The most serious symptoms affecting daily lives included urinary symptoms, unsatisfactory sexual life and hot flushes & sweating. And 391 (27.1%), 238 (16.5%), 285 (19.8%) and 296 (20.5%) women did not know the concept of perimenopausal syndrome, possible symptoms, health measures or symptoms requiring medical attention. The common methods of acquiring the knowledge of perimenopause were communicating with peers (458, 31.7%), consulting professionals (364, 25.2%) and searching health care information (225, 17.6%).


Conclusions
In women, the prevalence of perimenopausal syndrome remains quite high. And a majority of them lack a sufficient knowledge of perimenopause and need professional guidance.


Key words: 
Perimenopausal syndrome; Health service demand; Questionnaire
Deep-learning analysis of CT imaging biomarker for PD-L1 expression to predict heterogeneous response to immune checkpoint inhibitors in non-small cell lung carcinoma.
Authors: Jaehong Aum, Sehhoon Park, Soyoung Jeon, Eunji Lim, Hyunsuk Yoo, Ki Hwan Kim, Kyunghyun Paeng, Chan-Young Ock, Se-Hoon Lee, Ho Yun Lee
Journal: Journal of Clinical Oncology (2020)

e21529 Background: Inter-tumoral genomic heterogeneity cause various immune status in tumor microenvironment, which may lead to indiscriminate response to immune checkpoint inhibitor (ICI) in patients with multiple lesions. Therefore, PD-L1 status from practically approachable, single lesion would not be always representative for immune status of whole metastatic lesions of a patient. To solve inter-tumoral heterogeneity issue before biopsy in clinic, we developed a deep-learning based CT biomarker for predicting PD-L1 status, then explored if the algorithm would also predict ICI response of multiple lesions in non-small cell lung carcinoma (NSCLC). Methods: Deep learning-based image analyzer was trained with CT images of NSCLC in Samsung Medical Center (SMC) (N = 104). Taking 3D patch of a lesion located by radiologists, 3D convolutional neural network was trained to predict PD-L1 (22C3 immunohistochemistry) tumor proportion score of each lung or lymph node lesion. The prediction model was validated using publicly available dataset (NSCLC Radiogenomics, N = 115). Finally, we applied the model to baseline CT who had multiple lesions (≥ 2) and also received ICI (SMC validation, N = 170). Tumor response was assessed based on RECIST 1.1, and discordant response was defined by best response of each lesion outside -10% ~ +10%. Results: Predicted PD-L1 score was positively correlated with real PD-L1 expression in NSCLC Radiogenomics (Pearson = 0.198, P= 0.0339). In SMC validation cohort, predicted PD-L1 score of each lesion was negatively correlated with ICI response of corresponding lesion (Pearson = -0.0941, P= 0.0325). Interestingly, 35 out of 170 (20.6%) patients showing discordant ICI response among lesions had worse progression free survival (PFS) (median PFS: 2.1m, 1.6m, 2.5m, and 18.7m in discordant response, concordant progress, stable, and regress, respectively, P&lt; 0.001). Patients with discordant response had significantly wide-ranged predicted PD-L1 score compared with others (median range: 0.273 versus 0.185, P= 0.0079). Moreover, patient-level median of predicted PD-L1 scores of lesions was significantly associated with prolonged PFS (hazard ratio 0.69, P= 0.0401) and overall survival (hazard ratio 0.65, P= 0.0431). Conclusions: Deep-learning based imaging biomarker accurately predicts PD-L1 status of each metastasis, as well as independent ICI response reflecting inter-tumoral heterogeneity. This algorithm would guide which lesion would be representative in clinic.
Influence of age and cancer history on prevalence of autoimmunity in patients with metastatic melanoma: A large retrospective study.
Authors: Aaron N. Holmes, Xiaoyang Wang, Helen Swede, Upendra P. Hegde
Journal: Journal of Clinical Oncology (2020)

e22016 Background: While immune checkpoint inhibitors (ICIs) have improved the survival rates of metastatic melanoma in recent years, immune-related adverse events (irAEs) remain a major toxicity. Studies have established that pre-existing autoimmunity increases the risk of severe irAEs following ICI therapy (1). Melanoma is common cancer in older patients, and older age is believed to be a risk factor of autoimmunity. However, there is controversy concerning the influence of age increasing the risk of irAEs between clinical trials, which exclude patients with confirmed or suspected autoimmunity, and less-selective but lower-power case reports (2). In order to understand potential irAE risk following ICI treatment, we measured the prevalence of pre-existing autoimmune disease by age and cancer type. Methods: We studied 293,938 patients aged 18-106 years old who were treated at the University of Connecticut Health Center between 2000 and 2018 using GE Centricity’s IDX database. Patients were organized into four study groups based on International Classifications of Diseases codes (ICD-9 and ICD-10), specifically primary melanoma and three comparisons groups: non-cutaneous neoplasms alone, melanoma with non-cutaneous neoplasms, and patients without cancer history. A list of 340 ICD codes corresponding to 105 autoimmune conditions were queried. Results: Non-cutaneous cancer, in the absence or presence of melanoma, was associated with a higher prevalence of autoimmunity (27.0%, 29.4%, respectively) compared to the rates in patients with melanoma alone and those without cancer history (11.1%, 8.7%, respectively, p &lt; 0.05). In patients with both melanoma and non-cutaneous cancers, those with metastases had an 11.7% increase in autoimmune prevalence compared to patients without metastases (p &lt; 0.0001), the largest metastasis-associated increase observed across all cancer groups. Lastly, a logistic regression demonstrated that age is weakly correlated with autoimmunity (r = 0.01, p &lt; 0.0001). Conclusions: The findings suggest that a history of metastasis, non-cutaneous cancer, and advanced age are associated with a higher prevalence of pre-existing autoimmunity in melanoma patients. As ICIs are indicated for metastatic melanoma, our findings warrant future studies and careful risk assessment of autoimmunity in senior patients.
16例腕部电烧伤患者的治疗分析
Authors: 陈军, 王静, 杨加保, 张园园, 丁德武, 侯贺宪
Journal: BMJ (2009)

我院为矿业集团下属医院,长期为矿山救护服务.近年来矿山用电经常有意外触电事故发生,电损伤的发生率亦随之增加,而腕部接触电源机会也呈增长趋势.2001年5月至2006年10月,我科收治严重腕部(包括前臂远端、腕管以近部位)电烧伤患者16例,采用行早期姑息性扩创、保留间生态组织和有重要功能的神经肌腱组织,创面以组织瓣修复治疗,疗效满意。
Cumulative incidence of financial hardship in metastatic colorectal cancer (mCRC) patients (pts): Primary endpoint results for SWOG S1417CD.
Authors: Veena Shankaran, Joseph M. Unger, Amy Darke, Jennifer Marie Suga, James Lloyd Wade, Peter Kourlas, Sreenivasa R Chandana, Mark Allen O'Rourke, Suma Satti, Diane Liggett, Dawn L. Hershman, Scott David Ramsey
Journal: Journal of Clinical Oncology (2020)

137 Background: Despite evidence that rising cancer care costs contribute to “financial toxicity” in cancer pts, no studies, to our knowledge, have prospectively assessed the financial impact of cancer diagnosis (dx) using both self-reported and objective financial measures. S1417CD, led by the SWOG Cancer Research Network and conducted in the NCI Community Oncology Research Program (NCORP), was the first national prospective cohort study to evaluate time-to-first evidence of major financial hardship (MFH) in pts with newly diagnosed mCRC. We present results of the primary endpoint analysis. Methods: Pts age ≥ 18 within 120 days of mCRC dx receiving systemic treatment completed surveys every 3 months (mo) for 12 mo. MFH was defined as ≥ 1 occurrence of self-reported increase in debt, new loans, selling home, refinancing home, or ≥ 20% income decline during the 12 mo study period. Cumulative incidence (CI) of MFH was estimated to account for competing risk of death. Multivariate logistic regression was used to evaluate the association between pt characteristics with development of MFH. Results: 380 pts (median age 59.9) across 126 clinic sites were enrolled. Most pts were white (78%), male (61%), and insured (98%), with annual income ≤ $50,000 (56%). Cumulative incidence of MFH at 12 mo was 71.5% (95% CI: 65.9%-76.3%), with 24.6%, 52.4%, and 61.8% at 3, 6, and 9 mo; 104 (41%) pts reported ≥ 2 elements of MFH. Age, race, marital status, employment, and annual income (≤ vs. &gt; $50K) were not significantly associated with MFH. In a post hoc analysis, income &lt;$100,000 and total assets &lt;$100,000 were both adversely associated with MFH. Each increase in number of these 2 risk factors from 0 to 1 and 1 to 2 was associated with a 49% increased risk of MFH (p&lt;.001). Conclusions: In a national sample of mCRC pts on systemic tx, financial hardship, most commonly in the form of increased debt, accumulates progressively over time. Nearly 3 out of 4 pts experiencing MFH at 12 mo despite access to health insurance coverage. These findings underscore the need for clinic and policy solutions such as early financial navigation and elimination of cost sharing to protect pts from financial devastation as they continue with tx. [Table: see text]
A phase Ib adaptive study of dasatinib for the prevention of oxaliplatin-induced neuropathy in patients with metastatic colorectal cancer receiving FOLFOX chemotherapy and bevacizumab.
Authors: Anne M. Noonan, Maryam B. Lustberg, Patrick Schnell, John L. Hays, Ning Jin, Laith I. Abushahin, Pannaga G. Malalur, Sameek Roychowdhury, Rifat T. Elkhatib, Huizi Chen, Salwan Al Mutar, Alex Sparreboom, Shuiying Hu
Journal: Journal of Clinical Oncology (2020)

TPS12125 Background: Neurotoxicity is one of the most significant and disabling side effects of oxaliplatin and frequently limits the cumulative amount that can be used. The mechanism of oxaliplatin-induced neurotoxicity remains uncertain, although our preliminary studies suggest that oxaliplatin uptake by organic cation transporter 2 (OCT2) into mouse and rat dorsal root ganglion is a prerequisite for oxaliplatin-induced peripheral neuropathy. The activity of OCT2 is dependent on tyrosine phosphorylation by the SRC-kinase family member Yes1, which is highly sensitive to inhibition by several FDA-approved, small molecule kinase inhibitors such as dasatinib. We have previously shown that pre-treatment with oral dasatinib prevented acute and chronic oxaliplatin-induced peripheral neuropathy in mouse and rat models. Methods: This is a phase Ib dose-finding study of dasatinib given in combination with mFOLFOX6 with or without bevacizumab. The study explores the hypothesis that the addition of dasatinib prior to oxaliplatin will inhibit OCT2 activity and reduce oxaliplatin-induced neuropathy. This hypothesis will be tested in a Bayesian Phase 1b trial with adaptive dose selection using efficacy-toxicity trade-offs (modified toxicity-efficacy probability interval dose-finding design) in patients with confirmed stage IV colorectal cancer who are candidates for mFOLFOX6 with bevacizumab therapy. Patients who have documented peripheral neuropathy or prior exposure to oxaliplatin will be excluded. The primary objective is to determine the recommended Phase 2 dose which is defined as the lowest intermittent dose of dasatinib that affects serum biomarkers of OCT2, including methylnicotinamide and creatinine, by ≥2-fold without influencing the clearance of oxaliplatin by &gt; 20%. The following doses will be used: oxaliplatin 85mg/m 2 IV, 5FU bolus 400mg/m 2 IV bolus with Leucovorin 400mg/m 2 , bevacizumab 5mg/kg, followed by infusional 5FU 2400mg/m 2 IV over 46 hours given on a day 1 and 15 schedule every 28 days. Dasatinib will be administered at one of 2 dose levels – 100mg or 140mg po. Dasatinib will be given 24 hours and 30 mins prior to oxaliplatin on C1D14, C1D15 respectively and repeated on C1D28 and C2D1. Secondary objectives include evaluation of the influence of dasatinib on the pharmacokinetics of oxaliplatin and vice versa. Quality of life will be explored using the CIPN20 questionnaire. The trial opened to enrollment in Dec 2019 (NCT04164069) and is accepting patients. Clinical trial information: NCT04164069 .
释疑解惑
Authors: 尹德海, 朴元林, 吴群励
Journal: BMJ (2012)

问:临床所见糖尿病很多是在社区筛查中发现的,没有什么自觉症状,中医辨证也没有明显的偏颇,应该怎样治疗?答:随着医疗保健水平的提高,人们可以在例行体检或在社区糖尿病筛查中通过血糖水平的检测发现早期糖尿病患者或糖耐量异常者,从而达到早期防治.然而,对于这些没有明显自觉症状的早期患者,在中医临床诊治时,确实存在通过四诊无证可辨的情况,这确实是一个值得思考的问题。
Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19
Authors: Adrian V. Hernandez, Yuani M. Roman, Vinay Pasupuleti, Joshuan J. Barboza, C. Michael White
Journal: Annals of Internal Medicine (2020)

Hydroxychloroquine and chloroquine have antiviral effects in vitro against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).To summarize evidence about the benefits and harms of hydroxychloroquine or chloroquine for the treatment or prophylaxis of coronavirus disease 2019 (COVID-19).PubMed (via MEDLINE), EMBASE (via Ovid), Scopus, Web of Science, Cochrane Library, bioRxiv, Preprints, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and the Chinese Clinical Trials Registry from 1 December 2019 until 8 May 2020.Studies in any language reporting efficacy or safety outcomes from hydroxychloroquine or chloroquine use in any setting in adults or children with suspected COVID-19 or at risk for SARS-CoV-2 infection.Independent, dually performed data extraction and quality assessments.Four randomized controlled trials, 10 cohort studies, and 9 case series assessed treatment effects of the medications, but no studies evaluated prophylaxis. Evidence was conflicting and insufficient regarding the effect of hydroxychloroquine on such outcomes as all-cause mortality, progression to severe disease, clinical symptoms, and upper respiratory virologic clearance with antigen testing. Several studies found that patients receiving hydroxychloroquine developed a QTc interval of 500 ms or greater, but the proportion of patients with this finding varied among the studies. Two studies assessed the efficacy of chloroquine; 1 trial, which compared higher-dose (600 mg twice daily for 10 days) with lower-dose (450 mg twice daily on day 1 and once daily for 4 days) therapy, was stopped owing to concern that the higher dose therapy increased lethality and QTc interval prolongation. An observational study that compared adults with COVID-19 receiving chloroquine phosphate, 500 mg once or twice daily, with patients not receiving chloroquine found minor fever resolution and virologic clearance benefits with chloroquine.There were few controlled studies, and control for confounding was inadequate in observational studies.Evidence on the benefits and harms of using hydroxychloroquine or chloroquine to treat COVID-19 is very weak and conflicting.Agency for Healthcare Research and Quality.