tbuckley/cabot-search huggingface dataset:
Therapeutic effects of radiotherapy with concomitant and adjuvant temozolomide <i>versus</i> radiotherapy with concomitant temozolomide alone in children with DIPG: A single-center experience with 82 cases.
Authors: Mingyao Lai, Juan Li, Qingjun Hu, Shaoqun Li, Jiangfen Zhou, Cheng Zhou, Lei Wen, Zhaoming Zhou, Changguo Shan, Linbo Cai
Journal: Journal of Clinical Oncology (2020)

e14518 Background: To retrospectively analyze the therapeutic effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy with concomitant temozolomide alone for pediatric diffuse intrinsic pontine glioma (DIPG), and to evaluate the value of temozolomide in the treatment of pediatric DIPG. Methods: The clinical data of children with confirmed DIPG in Guangdong Sanjiu Brain Hospital between January 1, 2010 and December 30, 2019 were collected. The inclusive criteria included (1) receiving a total radiotherapy dose of 54 Gy in 27 fractions, (2) treated with concomitant temozolomide chemotherapy, and (3) with or without adjuvant temozolomide chemotherapy. Results: A total of 82 pediatric patients were eligible for the study, with a median age of 7 years (range 2-16 years). The median follow-up was 8.6 months (range 2-28 months) and the median survival time was 9.4 months. The median survival time of 66 patients treated with radiotherapy with concomitant and adjuvant temozolomide was 9.8 months, longer than 7.5 months of the other 16 patients treated with radiotherapy with concomitant temozolomide alone, with statistical differences (P= 0.010). Moreover, bevacizumab and nimotuzumab didn't bring survival benefits to patients with disease recurrence or progression. Hematological toxicity (Grade IV) was not found. Conclusions: Radiotherapy with concomitant and adjuvant temozolomide prolongs the survival time of children with DIPG.
A survey of nutritional and mental health condition in elderly community-dwelling males with chronic kidney disease
Authors: Xuli Liu, Qingli Cheng, Haibo Liu, Qiang Ma, Qinglin Li, Ruiqin Zhang, Zhiying Wang
Journal: BMJ (2014)

Objective
To explore the prevalence of chronic kidney disease (CKD) and evaluate their nutritional and mental health status in elderly community-dwelling males.


Methods
A stratified cluster random sampling method was used. A total of 436 senile males (≥80 years old) were recruited from 6 communities of Fengtai District, Beijing. After screening those with CKD, the risks of malnutrition were assessed by the mini nutritional assessment-short form (MNA-SF) plus anthropometric measurements and bio-chemical markers. And the mental health condition was measured by the Hopkins symptoms check list-10 (HSCL-10).


Results
① The prevalence of CKD in senile males of this study was 37.6%(n=164); ②According to the MNA-SF score, 9.1%(n=15)were malnourished and 25.0%(n=41) at the risk of malnutrition. From CKD stage 1 to stage 5, the prevalence of malnutrition and at the risk of malnutrition were 14.8%(n=4), 26.8%(n=11), 32.0%(n=16), 33.3%(n=8), 9/14, 8/8 respectively; ③The level of HSCL-10 score rose with the progression of CKD in senile males.


Conclusion
There is a high prevalence of CKD in elderly community-dwelling males. With the progression of CKD, their nutritional conditions and depression and anxiety symptoms worsen.


Key words: 
Nephrosis; Aged, 80 and over; Nutrition assessment
Analysis of risk factors for hypoalbuminemia in patients with apoplectic scquela
Authors: Jie Xu, Liu Cheng
Journal: BMJ (2012)

To retrospectively analyze the clinical data of 305 cases with apoplectic sequela admitted at our general geriatric nursing ward from January 2000 to December 2011.The subjects were divided into 2 groups:hypoalbuminemia and non-hypoalbuminemia.Advanced age (OR =5.624),chronic heart failure (OR =2.298),conscious disturbance (OR =1.575),dysphagia (OR =1.565),complete bedridden (OR=2.874),pneumonia (OR =3.725) and bedsore (OR =5.336) were risk factors for hypoalbuminemia in the patients with apoplectic sequela.And hyperglycemia(OR =0.066)was a protective factor for it.

Key words: 
Cerebrovascular accident; Hypoalbuminemia
FACT physical wellbeing to independently predict overall survival in patients with acute myeloid leukemia.
Authors: John Peipert, Fabio Efficace, Renee F. Pierson, Susan Yount, Christina Loefgren, David Cella, Jianming He
Journal: Journal of Clinical Oncology (2020)

7532 Background: Patient-reported outcomes (PROs) predict overall survival (OS) in solid cancer populations, but little evidence exists around the prognostic value of PROs in patients with hematologic malignancies. We investigated whether scales from the Functional Assessment of Cancer Therapy – Leukemia (FACT-Leu) predicted OS beyond established prognostic factors. Methods: Data were from 317 AML patients unfit for intensive therapy from a clinical trial comparing Dacogen (decitabine) plus Talacotuzumab versus Dacogen (decitabine) alone (AML2002; NCT02472145). We used ridge-penalized Cox models to determine whether baseline (1 st cycle) FACT-Leu scales predicted OS. FACT-Leu scales significant in these models and factors from a validated prognostic model, the AML composite model (AML-CL; covariates listed in Table), were entered into Cox proportional hazard models. Lastly, model selection procedures were run with 1000 bootstrapped samples using all variables. The inclusion frequency of each FACT-Leu scale in the final models was examined to evaluate prognostic value for OS (i.e., higher the % of inclusion, higher importance of the variable). Results: In the ridge-penalized Cox models, the Physical Wellbeing Scale (PWB), Trial Outcome Index (TOI), and FACT-Leu Total scales were significant predictors of OS. After adjusting for the AML-CL factors, an important difference (2 pts) in PWB score was associated with a 9% decline in OS. (Table) Model validity was evidenced as the PWB scale appeared in a large majority of selected models (90%-97%), while the TOI (45%-73%) and FACT-Leu Total (41%-71%) appeared less often. Conclusions: FACT-Leu scales, especially the PWB, were significant prognostic factors for OS among AML patients not suitable for intensive therapy. These results may indicate PROs' value as stratification factors in trials with AML patients and underscore the need to more systematically collect PRO data in routine care practice with AML patients. Clinical trial information: NCT02472145 . [Table: see text]
The effect of everolimus on adipose tissue in patients with metastatic breast cancer.
Authors: Ana Acuna Villaorduna, Heidi Ko, Orli Haken, June Deng, Janki Patel, Amanda Podolski, Laura Sofia Munoz-Arcos, Xiaoyang Wang, Jesus Del Santo Anampa Mesias
Journal: Journal of Clinical Oncology (2020)

e13026 Background: Obesity has been associated with negative outcomes in early breast cancer. Addition of everolimus (Eve) to endocrine therapy improves progression-free survival (PFS) in patients with hormone-receptor (HR) positive, HER2-negative metastatic breast cancer (MBC). Eve targets the mTOR signaling pathway which regulates cell growth/metabolism and has been implicated in obesity and diabetes. Changes in weight and body mass composition and its correlation with PFS have not been described in patients with MBC treated with Eve. We aim to compare total adipose tissue (TAT), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) before and after treatment with Eve in patients with HR+/HER2- MBC. Methods: Patients with metastatic HR+/HER2- MBC treated with Eve and endocrine therapy (Eve/ET) between 2012 and 2018 were identified. Each Eve/ET case was matched to a patient who received endocrine therapy alone (ET) by age at diagnosis (+/- 5 yrs), body mass index [BMI] (+/-5 kg/m2) and visceral metastatic disease. VAT, SAT, TAT, and skeletal muscle index (SMI) were measured by computerized tomography at L3 level using TOMOVISION software prior to treatment initiation (T0) and after 3-6 months of treatment (T3). TAT was defined as SAT + VAT and sarcopenia as SMI &lt; 40. Paired t-test and Wilcoxon paired-test were used to compare body composition parameters at T3 vs T0 in Eve/ET and ET groups. Results: 78 patients (Eve/ET: 41 and ET: 37) with a median age of 65.5 yrs were included. Of these, 16 (21.3%) were Non-Hispanic White, 31 (41.3%) were Non-Hispanic Black and 27 (36%) were Hispanics. Visceral metastases were seen in 57 (73.1%) cases. Mean weight, BMI, VAT and SAT at T0 were 70.8 kg, 27.4 kg/m 2 , 170.1 cm2 and 196.1 cm2, respectively and did not differ between Eve/ET and ET groups at baseline. At T3, there was a reduction in TAT (348.4 to 289.2 cm2, p &lt; 0.01) and SAT (181.7 to 142.7 cm2, p &lt; 0.01) in the Eve/HT group; while there were no significant changes in TAT (373.1 to 363.9 cm2, p = 0.39) or SAT (212 to 221.8 cm2, p = 0.33) in the ET group. No changes in visceral fat %, VAT/SAT ratio and sarcopenia between T0 and T3 in either treatment group were seen. In patients treated with Eve/ET, there were no differences in PFS between low TAT-loss (TAT loss &lt; 40 cm2) and high TAT-loss (TAT loss &gt; 40 cm2) (3.6 vs 4.8 months, p = 0.97). Conclusions: Eve induces TAT loss in patients with HR+/HER2- MBC, specifically driven by decrease in SAT. The pathophysiology of this association is still to be discerned. Further studies are required to evaluate TAT or SAT as a predictive/prognostic biomarker in patients receiving Eve.
Novel nanobiosensor based protease biomarkers for early detection and prognosis of pancreatic cancers.
Authors: Anup Kasi, James Kaiser Houghton, Anwaar Saeed, Stephen K. Williamson, Obdulia Covarrubias Zambrano, Stefan H Bossmann
Journal: Journal of Clinical Oncology (2020)

e16787 Background: Identifying novel biomarkers for early detection and prognosis would allow for improved survival outcomes in pancreatic cancer (PC). Arginase has been implicated in tumorigenesis through its production of L-ornithine. Its aberrant expression provides metabolites for tumor proliferation. Methods: In our study, 47 patients with metastatic PC, 29 with localized PC, and 50 healthy controls were enrolled at KU Cancer Center from 2000 to 2019. Overall survival (OS) was retrospectively assessed and correlated to serum protease levels at diagnosis. Protease expression was analyzed using nanobiosensors, which utilized fluorescent nanoparticles read by Spectra Scan to measure arginase, matrix metalloproteinases (MMPs), urokinase plasminogen activator (uPA), neutrophil elastase (NE), cathepsin B (CTSB), and cathepsin E (CTSE). Survival analysis was completed by Kaplan-Meier method. Results: Protease expression in localized vs. healthy cases was significant for (CTSB [p = 1.33E-10], MMP1 [p = 6.66E-21], MMP3 [p = 1.39E-13], MMP9 [p = 2.77E-08], NE [p = 0.00015], uPA [p = 2.55E-11]) and borderline significant for arginase [p = 0.05082]. Protease expression in metastatic vs. healthy cases was significant for (CTSB [p = 7.06E-06], MMP1 [p = 3.08E-12], MMP3 [p = 2.51E-14], MMP9 [p = 1.73E-08], NE [p = 0.01430], uPA [p = 0.00024]). Further, metastatic vs. localized cancer was significant for (arginase [p = 0.00034], CTSB [p = 0.00584], MMP1 [p = 2.03E-13], NE [p = 2.29E-10], and uPA [p = 6.58E-07]. Characteristics of 21 localized PC patients are illustrated in Table. Median OS was 25m in localized PC with low Arginase expression (mean &lt; 215) vs 17.5m in high Arginase expression (p = 0.0477). Conclusions: Expression pattern of CTSB, MMP, NE, arginase, uPA proteases showed statistical significant difference for detection of localized PC vs metastatic PC vs healthy cases. In localized PC, lower arginase expression showed a statistically significant improvement in survival vs high arginase expression. Arginase expression was borderline significant for detection of localized PC vs healthy controls, likely due to small sample. Arginase as a potential biomarker for early detection and prognosis of PC warrants validation in a larger cohort. [Table: see text]
A prognostic and predictive nomogram for patients with resected pancreatic cancer and the effect of adjuvant chemotherapy in different risk groups: Data from two large cohorts in Taiwan.
Authors: Hsu Wu, Jhe-Cyuan Guo, Shih-Hung Yang, Jen-Shi Chen, Ta-Sen Yeh
Journal: Journal of Clinical Oncology (2020)

e16762 Background: Wide survival difference of pancreatic cancer in the same TNM stage had been demonstrated. Predictive nomogram for resected pancreatic cancer had been published before, but the impact of adjuvant chemotherapy was not incorporated, and the data of Asian people were lacking. We also evaluated the effect of adjuvant chemotherapy in different risk groups according to our nomogram. Methods: Pancreatic cancer patients who underwent curative surgery between 2000/1 and 2013/12 were collected from the Cancer Registry of NTUH as the training cohort. Another cohort from CGMH was studied as the validation cohort. Analyses were performed by IBM SPSS version 21.0. Age, gender, primary tumor location, tumor differentiation, LVI, PNI, T, N, AJCC 7 th stage, section margin, and adjuvant chemotherapy were used for univariate and multivariate analysis. Nomogram was built and validated by software R 3.6.1. C-index was used to demonstrate the performance and discrimination ability of nomogram. Results: There were 319 and 245 patients in NTUH and CGMH cohorts. The R0 resection rates were 80.6 and 71.8%, and 24.5 and 63.7% of patients received adjuvant chemotherapy. Median OS were 16.9 and 15.7 months in NTUH and CGMH. AJCC 7 th Stage, tumor differentiation, section margin, tumor location, LVI and receiving adjuvant chemotherapy were incorporated in the nomogram. C-index in NTUH cohort was 0.66 (95% CI: 0.62-0.70), which was higher then C-index of AJCC 7 th Stage, 0.58 (95% CI: 0.54-0.61). The C-index in the CGMH was 0.65 (95% CI: 0.60-0.69). We grouped the two cohorts into low, medium, and high risk groups according to the nomogram score. In NTUH, there were 50, 208, and 48 patients in the low, medium, and high risk groups. In CGHM, there were 37, 156, and 45 patients in those groups. The Kaplan-Meier curves of OS separated nicely according to different risk groups (log rank p &lt; 0.001). If excluding adjuvant chemotherapy in nomogram, C-index in NTUH was 0.63 (95% CI: 0.59-0.67) and 0.62 (95% CI: 0.58-0.66) in CGMH by the new nomogram. The relative survival hazard ratios of receiving adjuvant chemotherapy were 0.532, 0.626, and 0.358 in high, medium and low risk groups of NTUH and were 0.624, 0.798, and 0.788 in CGMH. Conclusions: The new nomogram with more clinical factors than TNM stage has better prognostic prediction. We add the impact of adjuvant chemotherapy into our predictive model. Adjuvant chemotherapy is important in resected pancreatic cancer, even in low risk population.
抗精神病药物和消毒剂污染对尿常规检测结果的影响
Authors: 郭新胜, 李玉凤, 高元法, 高耀东
Journal: BMJ (2005)

对1 265例住院精神病患者尿常规检测结果与临床符合率做统计分析时发现,有60例结果与临床不符.主要原因集中在:临床上使用大剂量的抗精神病药物,占82.4%(14/17);在标本留取过程中被消毒剂污染占82.1%(32/39)。
Effectiveness of thymosin alpha-1 on patients with severe community-acquired pneumonia
Authors: Xin-hua He, Chun-sheng Li, Hai-yan Zhang, Lu-hui Shen
Journal: BMJ (2009)

To investigate the effectiveness of thymosin a1 on patients with severe community-acquired pneumonia (SCAP). Methods Thirty-five patients with SCAP were randomly divided into two groups, group A with regular treatment as control and group B with both thymosin a1 and regular treatment. Venous blood specimens were collected from them before treatment (baseline) and seven days after treatment for laboratory testing, including serum concentrations of c-reactive protein (CRP) and albumen (ALB), serum activities of aspartate aminotransferase (AST) and aniline aminotransferase ( ALT), and percentage of T-lymphocyte subsets CD3+ , CD+ and CD8+ by indirect immunofluorescence. Meanwhile, their symptoms, signs and chest X-ray were observed. Length of mechanical ventilation and stay at emergency intensive care units (EICU) of the patients were recorded. Results Percentages of CD3+ and CD4+ , and ratio of CD+ to CD8 + increased significantly and percentage of CD8+ reduced significantly in group B seven days after treatment, as compared to those before treatment [ (46.3 ± 5.3) % vs. (29.9 ± 2.1 ) %, (44.5 ± 5.2) % vs. (28. 7 ± 2. 8 ) %, and 1.8 ± 0. 4 vs. 0. 9 ± 0. 1, respectively, P   0.05 ) . Length of mechanical ventilation and stay at EICU were significantly shorter in group B than those in group A [ ( 8.4 ± 2.7 ) d vs. ( 5.1 ± 1.6 ) d, P  0.05).Conclusions Immune status of patients with SCAP could be improved by thymosin a1, with a shorter length of mechanical ventilation and stay at EICU, to promote their recovery.

Key words: 
Thymosin hormones;  T-lymphocyte subsets;  Community-acquired infections
Technical validation of PD-L1 SP142 assay for TNBC in a large academic center: Unexpected challenges.
Authors: Sharon Nofech-Mozes, Elzbieta Slodkowska
Journal: Journal of Clinical Oncology (2020)

e15253 Background: The IMpassion 130 trial reported that 41-46% of TNBC are positive for PD-L1 SP142 based on centralized testing. While the FDA approved it as a companion diagnostic assay with cut off value of 1%, there are no published guidelines for technical validation in local laboratories. Furthermore, with the need to evaluate staining only in inflammatory cells (IC) the readout becomes particularly challenging for cases around the cutoff point. We report our prevalence of PD-L1 positivity and proportion of borderline cases in our validation. Methods: We ran PDL1 SP142 using the recommended protocol from Roche on the following groups: G1 - 53 consecutive TNBC cases (excisions tumors ≥7mm), G2 - 10 consecutive TNBC cases (breast specimens only) that would have met the inclusion criteria for the trial (LABC with poor NAT response or metastatic), G3 – proficiency testing slide from an EQA provider (4 cores of TNBC 1 negative, 1 borderline low positive and 2 high positive). All cases were read by 2 breast pathologists that received training on PDL1 readout by Roche (one – in class and online, one – online). Results: Borderline staining around the 1% cutoff (11 of 63) and low positive (9 of 63) were encountered in the validation sets more often than shown in training sessions. Classification of borderline cases may have a substantial impact on the rate of PDL1 positivity that potentially could approach 75%. Borderline cases often have IC staining either at the advancing tumor edge, as small collections of highly positive IC or around benign ducts entrapped within the tumor. Conclusions: The prevalence of PDL1 positive TNBC in all comers could be higher than observed in IMpassion 130 (at least 50-60%). Pathologist training in readout is of utmost importance due to high rate of borderline/low positive cases raising the need for central testing in borderline cases. Guideline recommendations for technical validation similar to other class II biomarkers would be useful. Studies on interobserver variability are needed to further address this potential issue. [Table: see text]
A randomized phase II study of gemcitabine (G) alone or with pazopanib (P) in refractory soft tissue sarcoma (STS).
Authors: Christopher W. Ryan, Catherine Degnin, Lee D. Cranmer, Yiyi Chen, Seth Pollack, Jesse Tonkinson, Phillip Norr, Lara E. Davis
Journal: Journal of Clinical Oncology (2020)

11515 Background: Both G and P are active single-agents in the treatment of STS. We hypothesized that the anti-VEGF-R activity of P could augment the efficacy of G and conducted this study of G+P vs G+placebo (0). Methods: In this multi-center, double-blind study, eligibility included metastatic STS with receipt of 1–3 prior systemic regimens inclusive of an anthracycline. Patients (pts) were stratified by sarcoma subtype (liposarcoma (LPS) vs. other) and study site, then randomly assigned 1:1 to receive G 1000 mg/m2 IV over 30 minutes on days 1 and 8 every 21 days plus either P 800 mg PO or matching 0 daily. The primary endpoint was progression-free survival (PFS). Results: 54 pts were accrued from 2012–2019, Accrual was halted prior to the planned N of 80 due to withdrawal of funding. There were no differences in pt characteristics between the two arms including age (median = 60), sex (M/F 52/48%), histology (LPS 30%, leiomyosarcoma 26%, UPS 15%, synovial 11%, other 17%) and number of prior systemic therapies (median = 1). With a median follow-up of 19.1 months, PFS favored G+P and was significant using the Gehan-Wilcoxon test which favorably weighs earlier events (table). The response rate was 6.9% on the G+P arm and 8.0% on the G+0 arm; response rate was 22% for LPS treated with G+P. The most common grade ≥3 AEs (G+P v G+0) were: neutropenia (41% vs 40), hypertension (17% v 4), anemia (7% v 12). One patient died of hepatic failure on the G+P arm. Conclusions: This study demonstrated improved PFS with G+P as compared with G alone. Early termination limited statistical power. G+P is active in LPS, although P regulatory labeling currently limits use for LPS. Clinical trial information: NCT01532687 . [Table: see text]
SARS-CoV-2 infection and overactivation of Nlrp3 inflammasome as a trigger of cytokine “storm” and risk factor for damage of hematopoietic stem cells
Authors: Mariusz Z. Ratajczak, Magda Kucia
Journal: Leukemia (2020)

Abstract The scientific community faces an unexpected and urgent challenge related to the SARS-CoV-2 pandemic and is investigating the role of receptors involved in entry of this virus into cells as well as pathomechanisms leading to a cytokine “storm,” which in many cases ends in severe acute respiratory syndrome, fulminant myocarditis and kidney injury. An important question is if it may also damage hematopoietic stem progenitor cells?
Atezolizumab and platinum-based chemotherapy in extensive-stage small cell lung cancer: A single center experience.
Authors: MARKO JAKOPOVIC, Lela Bitar, Kristina Krpina, Fran Seiwerth, Ante Marusic, Sanja Plestina, Suzana Kukulj, Mihovil Roglic, Marta Korsic, Sonja Badovinac, Miroslav Samarzija
Journal: Journal of Clinical Oncology (2020)

e21110 Background: In extensive stage small-cell lung cancer (ES-SCLC) immune check-point inhibitors, atezolizumab and durvalumab, when combined with chemotherapy in the first-line setting show better efficacy than chemotherapy alone with safety profile similar as the adverse events of individual agents. Methods: We administered atezolizumab, etoposide and platinum, either carboplatin or cisplatin, in the first-line treatment in 24 newly diagnosed patients with ES-SCLC. Patients were treated until disease progression or unacceptable toxicity. Results: Out of 24 treated patients 13 were males and 11 were females, median age 61 (ranging from 44 to 80). Majority of patients were ECOG 1. Median number of atezolizumab doses was 8 (ranging from 2 to 11). We observed median progression free survival of 6 months (95%CI 4,28-7,72), while median overall survival was not reached. 10 patients (41%) are still undergoing treatment and 9 patients (37%) have died. Immune-related adverse events occurred in 6 patients (25%). Four patients developed pneumonitis (all of them CTCAE grade 2), two patients colitis (CTCAE grade 2 and 3) and one patient rash, CTCAE grade 3. Median treatment pause was 5 weeks (ranging from 3 to 12 weeks). There were no treatment discontinuations due to adverse events nor treatment related deaths. Conclusions: Atezolizumab combined with chemotherapy in ES-SCLC showed good tolerability and effectiveness in real world setting. Our data are consistent with published clinical trial data. There was no new safety signal in our patient cohort. Limitations of our report are small sample size and short follow-up time.