tbuckley/cabot-search huggingface dataset:
Tisagenlecleucel (Tisa) for relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL): B2001X study focusing on prior exposure to blinatumomab (BLINA) and inotuzumab (INO).
Authors: Joerg Krueger, Henrique N. S. Bittencourt, Susana Rives, Andre Baruchel, Barbara De Moerloose, Christina Peters, Peter Bader, Jochen Buechner, Nicolas Boissel, Hidefumi Hiramatsu, Karen Thudium, Prasanthi Sanjeevi, Marina White, Lamis K. Eldjerou, Adriana Balduzzi
Journal: Journal of Clinical Oncology (2020)

10518 Background: B2001X (NCT03123939) is a multicenter global study of tisa to provide access to patients (pts) with r/r ALL including prior anti-CD19 therapy after enrollment ended in the pivotal ELIANA (NCT02435849) study. We report clinical outcomes and cellular kinetics in B2001X including pts with prior BLINA exposure or INO as bridging therapy (BT). Methods: Eligible pts ≤21 y at diagnosis with ≥2 relapse, refractory or post allogeneic transplant (alloSCT) relapse were enrolled globally. Results: As of Nov 4, 2019, 73 pts were enrolled; 67 received tisa. 91% received lymphodepletion. Among 65 pts ≥3 mo follow up (FU) or discontinued earlier (efficacy analysis set [EAS]) median FU was 9.6 mo (range [R] 0.2-16.5). Median age 10 y (R 2-33); prior alloSCT 61%; 15 pts had prior BLINA and 9 pts had INO as BT. Efficacy is summarized in Table. 13/14 relapsed pts were medullary (isolated or combined with extramedullary [EM]) and 1 EM; 9 within 6 mo including 4/5 who were CD19(+). 64% had CRS (G 3/4 13%/15%; Penn scale); 24% had neurologic events (G 3/4 9%/2%; CTCAE v4.03). 4 deaths ≤30 d: 2 early ALL progression, 1 fatal CRS with refractory ALL, 1 infection with multiorgan failure. Transgene level in peripheral blood: limited to no in vivo expansion in nonresponders (n=8) vs responders (n=42). Median duration of persistence (T last) of tisa was 272 d (R 27-379) in responders. In pts with CR/CRi, C max (geo-mean [CV%]) and median T last were 9260 (124) copies/µg DNA and 154 d (R 28-349), respectively, in pts who received INO as BT (n=6) vs 38,500 (215) and 273 d (R 27-379), respectively, in pts with no INO as BT (n=36). Conclusions: Outcomes in B2001X remain consistent with ELIANA. In pts with prior BLINA or INO as BT, a trend toward suboptimal outcomes was observed but should be interpreted with caution due to small n, short FU and potential confounding factors. Clinical trial information: NCT03123939. [Table: see text]
Radiosurgery in Patients With Small Cell Lung Cancer With Brain Metastases
Authors: Cecile Le Pechoux, Antonin Levy
Journal: JAMA Oncology (2020)

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Rural and urban disparities based on zip code of residence: Analyses of 834 and 2,159 patients in NCCTG N9741 and CALGB 80405 (Alliance) trials respectively.
Authors: Midhun Malla, Lucas J. Huebner, Sorbarikor Piawah, Heinz-Josef Lenz, Charles David Blanke, Jeffrey A. Meyerhardt, Eileen Mary O'Reilly, Qian Shi, Alan P. Venook, Richard M. Goldberg
Journal: Journal of Clinical Oncology (2020)

e16076 Background: Median overall survival (mOS) of patients (pt) with metastatic colorectal cancer (mCRC) has improved steadily over the past two decades. However, epidemiological data suggest that cancer outcomes for rural compared to urban dwelling pts are worse. In this study, we retrospectively compared progression free survival (PFS) and OS among mCRC pts residing in urban versus rural areas enrolled in N9741 (1997-2004) and CALGB 80405 (2005-2012) clinical trials. Methods: Zip code data from the Centers for Disease Control (CDC) were used to classify pts into rural or urban dwellers. Chi-square and Kruskal Wallis analyses were used to compare the groups. Survival outcomes were evaluated using Kaplan-Meier estimates, compared by stratified log rank and cox proportional hazards models. Results: In N9741 and 80405 respectively, 217 (35%) and 521 (21%) pts resided in rural areas. Median age of mCRC pts at diagnosis was 60.5 yrs. (rural) compared to 58.6 yrs. (urban) in 80405 (P &lt; 0.01) and 59.6 yrs. to 60.2 yrs. in N9741 (P = 0.4). In 80405, pts in rural areas were less likely to be female (35% vs 43%, P &lt; 0.01) black (6.6% vs 15.1%, P &lt; 0.01), unmarried (51% vs 62%, P &lt; 0.01), and to have private insurance (PI) (45% vs 50%, P = 0.03) when compared to pts in urban areas. In N9741, gender (P = 0.8) and PI (P = 0.3) distribution was similar; pts in rural areas were less likely to be black (1.4% vs 9.1%, P &lt; 0.01). Rural vs urban pt PFS was no different in either trial. MOS was worse in pts in rural areas when compared to urban dwellers in 80405 (Table). OS outcomes stratified based on the use of cetuximab based regimen in 80405 showed worse outcomes for pts in rural compared to urban dwellers (21.9 vs 26.3 mo. HR: 1.22 (1.03-1.44), P = 0.02). Conclusions: MCRC pts from rural areas had a significantly worse mOS when compared to pts in urban areas in 80405. Furthermore, mOS with cetuximab based regimens was 4.4 months shorter in rural pts. The observed rural vs urban dweller mOS disparities in 80405 pts justifies additional research searching for causal factors and the necessity to identify actionable approaches in order to improve pt outcomes in rural areas. Support: U10CA180821, U10CA180882, U10CA180888, UG1CA180830; Pfizer, Sanofi, BMS, Genentech, https://acknowledgments.alliancefound.org . ClinicalTrials.gov Identifier: NCT00003594, NCT00265850. [Table: see text]
补钾致高钾血症二例
Authors: 谷传凯, 李海峰, 刘方清
Journal: BMJ (2007)

例1 患者女,78岁,于2005年9月20日因脑梗死入院.有高血压病史10年.入院检查血K+4.26 mmol/L;血尿素氮5.10 mmol/L,肌酐97μmol/L;心电图示冠状动脉缺血性表现.患者于9月23日出现左心衰竭症状,予速尿20mg口服,每日2次,共用15 d;螺内酯(安体舒通)20 mg口服,每日2次,共用15 d;并予缬沙坦80 mg口服,每日1次,至出院.予10%氯化钾5 ml入液,每日1次,20%枸橼酸钾10 ml口服,每日3次,共用22 d。
Abstract 11839: Hepatitis C sero-positivity Adversely Affects Long-term survival After Orthotropic Heart Transplant: Fifteen Year Analysis of a National Registry
Authors: Sachin Kumar, Salil V Deo, Salah E Altarabsheh, Shannon M Dunlay, Basar Sarreyyupoglu, Yakov Elgudin, Benjamin Medalion, Chantal ElAmm, Mahazarin Ginwalla, Guilherme H Oliveira, Greg Fonarow, Soon J Park
Journal: Circulation (2015)

Background: Concerns exist regarding orthotropic heart transplantation (OHT) in hepatitis C (HCV) seropositive recipients. The UNOS national registry was accessed to evaluate HCV recipient sero-positivity and outcomes. Method: Retrospective analysis of the UNOS registry (2000-2014) to evaluate recipient profile and clinical outcome of HCV sero-positive (HCV+ve) and sero-negative (HCV -ve) pts. Early and late adjusted survival and adverse events at follow-up were compared. Results: From 23,507 patients (mean age 52 yrs; 75% male), 481 (2%) were HCV +ve (mean age 52 yrs; 77% male). Annual proportion of HCV +ve recipients was comparable over the study period (range 1.3-2.7%; p=0.2). The HCV +ve cohort had more African American (22% vs 17%; p=0.01), pts with a prior LVAD (21 vs 14%; p&lt;0.01 and more hepatitis B core Ag+ve recipients (17% vs 5%; p&lt;0.01). However, ECMO (p=0.7), inotropic (p=0.2), and intra-aortic balloon pump (p=0.7) support, serum creatinine (p=0.7) and serum bilirubin (p=0.7) were similar. Proportion of Status 1A pts was similar (24% HCV+ vs 21% HCV -); however wait-time for HCV + recipients was longer (mean 23 vs 19 days; p&lt;0.01). Among donor variables, age (p=0.8), hepatitis B status (p=0.4) and CDC high risk status (p=0.9) were comparable. At a median follow up of 4 years, 67.1% patients were alive, 28.4% died and 1.1% were re-transplanted (3.4% missing). Overall survival was worse in the HCV+ cohort (64.3 vs 72.9 % and 43.2 vs 55% at five and ten years; p&lt;0.01). Late renal [OR 1.2(1-1.6); p = 0.02] and liver dysfunction [OR 4.5 (1.2-15.7); p=0.01] occur in HCV +ve recipients. On adjusted analysis, HCV sero-positivity is associated with poorer survival [HR0.6 (0.5-0.8); p&lt;0.01]. Conclusion: A small proportion of patients receiving a heart transplant in the United States have hepatitis C. In spite of comparable pre-operative hepatic function, hepatitis C sero-positive recipients develop late liver dysfunction and have poorer long-term survival.
Do <scp>C</scp>heyne and <scp>S</scp>tokes have an important message for modern‐day patients with heart failure? <scp>Y</scp>es, they do
Authors: Massimo F. Piepoli, Piotr P. Ponikowski, Maurizio Volterrani, Darrel P. Francis, Andrew J.S. Coats
Journal: European Journal of Heart Failure (2020)
Trastuzumab-induced cardiotoxicity and hypertension among racially and ethnically diverse patients with HER2-positive early-stage breast cancer.
Authors: Monica F. Chen, Daniel K. Manson, Ariel Yuan, Katherine D. Crew
Journal: Journal of Clinical Oncology (2020)

e24092 Background: Trastuzumab improves breast cancer survival but is associated with an increased risk of heart failure. Identifying risk factors associated with trastuzumab induced cardiotoxicity (TIC) would allow for more targeted and intensive screening for at-risk patients. Hypertension is one of the most consistent predictors of TIC. Racial/ethnic minorities are at higher risk of cardiovascular disease but are under-represented in studies of TIC. The objective of this study was to evaluate the relationship between race/ethnicity and risk of TIC among a diverse cohort of patients with HER2-positive early-stage breast cancer. Methods: We conducted a retrospective cohort study of patients treated at Columbia University between 2007 and 2016 for stage I-III breast cancer with adjuvant or neoadjuvant trastuzumab who had at least two echocardiograms. Mild TIC was defined as a ≥10% decline in left ventricular ejection fraction (LVEF); moderate TIC ≥15% decline; severe TIC ≥20% or decline in LVEF to &lt; 50%. Diagnosis of hypertension, average systolic and diastolic blood pressure, and number of hypertension medications was assessed 1- year pre-treatment, during treatment, and 1-year post-treatment. We generated descriptive statistics and used multivariable logistic regression to evaluate demographic and clinical factors associated with TIC. Results: Of 279 patients evaluated, 36.6% were non-Hispanic white, 18.3% non-Hispanic black, 34.8% Hispanic, and 10.4% Asian. The average baseline LVEF was 60% and did not significantly differ between racial/ethnic groups. Mild TIC developed in 33.3% of patients, moderate TIC 18.6%, severe TIC 15.8%, and 14.7% with LVEF decline to &lt; 50%. Patients with hypertension were at increased odds of developing TIC (OR = 2.41, 95% CI = 1.15-3.93; p = 0.02). Prevalence of hypertension was 53% among non-Hispanic white women, 69% non-Hispanic black, 53% Hispanic, and 39% Asian. Incidence of TIC did not differ significantly between racial/ethnic groups. Forty percent of patients with hypertension were not on any medications before initiating trastuzumab. Conclusions: There was no difference in TIC based upon race/ethnicity despite higher rates of hypertension among racial/ethnic minorities compared to non-Hispanic whites. However, a high portion of patients with hypertension were not on any medications before treatment. Increased screening and treatment of hypertension among patients receiving HER2-positive targeted therapy for early-stage breast cancer may be warranted.
Key issues in the development and approval of new anti-cancer immune therapies.
Authors: Al Blunt, Steve Gyorffy, Gerald L. Messerschmidt
Journal: Journal of Clinical Oncology (2020)

e15232 Background: Immunotherapy (IT) is now an established treatment option for a select group of cancer patients, and holds great promise for broader application. However, the number of new IT drug approvals has remained low, despite hundreds of new immune therapies entering clinical trials. Methods: We examined both successes and failures of immune-therapeutics (small molecules, large molecules and cellular therapies) to develop insight into this trend. We searched multiple public data sources including clinicaltrials.gov, PubMed, and other large data bases to identify informative trials and primary endpoints. A key area of our research focus was the rate of objective tumor responses following treatment with the immunotherapy agents. Results: Our main observation was that most clinical trials in solid tumors were characterized by a low rate of objective response. Tumor shrinkage is known to be the final manifestation of a multi-step process that begins with the therapeutic product’s ability to bind to its target, and the subsequent engagement of pathways that result in tumor infiltration and tumor cell destruction. A critical step is a sustained immune effector cell attack on the tumor cells. However, a growing body of evidence supports the concept that both non-cellular and cellular immune therapies are active primarily in the setting of a “very warm” or “hot” tumor microenvironment (TME). We found evidence of a positive correlation between objective responses and the degree of ‘hotness’ of the TME. Importantly, our research indicates that study drugs were typically successful in precisely engaging their targets in the associated pathway. High response appears to require selection of appropriate populations with respect to tissue/organism level pathways that lead to successful tumor destruction. Conclusions: The success of IT drugs requires clinical trial designs based on insight into both the study drug’s target pathway, and the impact of key organism level physiologic processes, (e.g., TME) that interfere with optimal anti-tumor activity. [Table: see text]
Detection of urinary neutrophil gelatinase associated lipocalin and blood prohibitin levels in early diagnosis of children with acute kidney injury
Authors: Haifeng Wang, Tongde Ruan, Min Gao, Huiwen Zhuang, Meng Xu
Journal: BMJ (2016)

Objective
To assess the detection of urinary neutrophil gelatinase associated lipocalin (NGAL) and blood prohibitin (PHB) levels in early diagnosis of children with acute kidney injury (AKI).


Methods
One hundred and twenty children with severe allergic purpura, sepsis, kidney disease or heart disease admitted from June 2011 to June 2013 in our hospital were enrolled, including 60 cases with AKI and 60 cases without AKI; and 60 healthy children were selected as the control group. The urinary NGAL and blood PHB levels were measured with ELISA method.


Results
At d1 after diagnosis, the urinary NGAL level in severe AKI group[(146.76±61.22) μg/L]was higher than that in non-AKI group[(21.79±17.31) μg/L]and control group[(17.42±13.11) μg/L](t=15.430 and 22.216, P<0.01). At d2 after diagnosis, the urinary NGAL level in severe AKI group[(82.31±44.76) μg/L]was higher than that in non-severe AKI group[(21.56±28.56) μg/L](t=8.863, P<0.01). At d1 of diagnosis, the blood PHB level in severe AKI group was higher than that in non-severe AKI group[(14.03±6.43) vs. (8.01±6.13), t=11.271, P=0.004]; blood PHB in severe AKI group was higher than that in non-AKI group[(10.63±4.21) vs. (8.00±4.76), t=7.051, P=0.017]. The levels of urinary NGAL and serum PHB gradually decreased over time in children with severe AKI. The area under the ROC curve (AUC) of urinary NGAL and blood PHB for diagnostic of AKI were 0.833 and 0.952 (P<0.01), respectively. The diagnostic rate of the combination of the two parameters was 100%.


Conclusions
The diagnostic value of PHB alone or NGAL in AKI still may be improved. The detection of PHB combined with NGAL can make up each other and improve the diagnosis of AKI, which contribute to the early diagnostic of AKI for clinical workers and provide effective intervention measures, and then reduce the mortality.


Key words: 
Prohibitin; Neutrophil gelatinase associated lipocalin; Acute kidney injury; Child
Clinical and endoscopic features of esophageal ulcers in relation to differential diagnosis of benign and malignant lesions
Authors: Hongmei Yu, Wei Tan, Lei Shen
Journal: BMJ (2014)

The clinical features and endoscopic findings of 50 with esophageal ulcers were retrospectively reviewed.The ratio of male to female was 3.5∶1 (39∶11, P 0.05). However deep, large (≥2.5 cm) and irregular esophageal ulcers were more likely to be malignant (P<0.01). The clinical and endoscopic findings reveal that the malignancy of esophageal ulcer is correlated with the size, depth and shape of the lesions.


Key words: 
Esophageal; Ulcer; Endoscopy, Digestive system
Significant antitumor activity for low-dose ipilimumab (IPI) with pembrolizumab (PEMBRO) immediately following progression on PD1 Ab in melanoma (MEL) in a phase II trial.
Authors: Daniel Olson, Jason J. Luke, Andrew Stewart Poklepovic, Madhuri Bajaj, Emily Higgs, Timothy C. Carll, Brian Labadie, Thomas Krausz, Yuanyuan Zha, Theodore Karrison, Jose Lutzky, Sigrun Hallmeyer, Bruce Brockstein, Vernon K. Sondak, Zeynep Eroglu, Thomas Gajewski, Nikhil I. Khushalani
Journal: Journal of Clinical Oncology (2020)

10004 Background: Combination PD1 + CTLA4 antibodies (Abs) shows greater response rate (RR) versus PD1 Ab alone in MEL, but RR after initial PD1 Ab progression awaits robust investigation. CTLA4 Ab alone after PD1 Ab progression has a historical RR of 13%. We report final results of the first prospective clinical trial evaluating IPI 1mg/kg + PEMBRO immediately following progression on PD1 Ab (NCT02743819). Methods: Patients (pts) with advanced MEL, no prior CTLA4 Ab for metastatic disease, and who had progressed on PD1 Ab as immediately prior therapy (or non-CTLA4 Ab combination) were eligible. Pts received PEMBRO 200 mg + IPI 1 mg/kg Q3W for 4 doses, then PEMBRO alone for up to two years. The primary endpoint was RR by irRECIST. After 35 pts, the study met its primary endpoint with 10/22 evaluable pts achieving a response. The trial was expanded to enroll a total of 70 pts in open-label accrual to further describe the RR for this regimen in an exploratory fashion. The data analysis cutoff was January 30, 2020. Results: 67/70 accrued patients were evaluable for treatment response. Prior treatments included 60 on PD1 Ab alone and 10 on PD1 Ab-based combinations. Of these, 10 pts had progressed in the adjuvant setting. Median length of treatment on prior PD1 Ab was 4.8 months. Response assessments included 4 CR, 17 PR and 16 SD for a RR of 31% (21/67) in evaluable pts, and 30% (21/70) in all enrolled pts. 4 pts with a PR and 6 with SD had unconfirmed responses making the irRECIST response rate 25% (17/67) and 24% (17/70) among evaluable and enrolled pts, respectively. Median progression free survival (PFS) was 4.7 mo (95% CI: 2.8-8.3) and PFS at six months was 45% (95% CI: 33%-57%). 15/70 (21%) pts experienced ≥ grade 3-4 drug-related AEs, the most common being diarrhea, rash and transaminase elevation. PD-L1 positive vs negative status from historical tumor specimens did not associate with RR. Conclusions: This is the largest prospective study of IPI 1mg/kg + PEMBRO, demonstrating significant antitumor activity and tolerability in MEL post-PD1 Ab. Clinical trial information: NCT02743819.
Overall survival (OS) results of phase III ARAMIS study of darolutamide (DARO) added to androgen deprivation therapy (ADT) for nonmetastatic castration-resistant prostate cancer (nmCRPC).
Authors: Karim Fizazi, Neal D. Shore, Teuvo Tammela, Albertas Ulys, Egils Vjaters, Sergey Polyakov, Mindaugas Jievaltas, Murilo Luz, Boris Alekseev, Iris Kuss, Marie-Aude Le Berre, Oana Petrenciuc, Amir Snapir, Toni Sarapohja, Matthew Raymond Smith
Journal: Journal of Clinical Oncology (2020)

5514 Background: DARO is a structurally distinct androgen receptor inhibitor with a favorable safety profile, approved for treating men with nmCRPC after demonstrating significantly prolonged metastasis-free survival, compared with placebo (PBO), in the phase III ARAMIS trial: median 40.4 vs 18.4 months, respectively (HR 0.41; 95% CI 0.34–0.50; P&lt;0.0001). We report final analyses of OS and prospectively collected, patient-relevant secondary endpoints, and updated safety results. Methods: 1509 patients (pts) with nmCRPC were randomized 2:1 to DARO 600 mg twice daily (n=955) or PBO (n=554) while continuing ADT. Secondary endpoints included OS, and times to pain progression, first cytotoxic chemotherapy, and first symptomatic skeletal event. The OS analysis was planned to occur after approximately 240 deaths. Secondary endpoints were evaluated in a hierarchical order. Results: Final analysis was conducted after 254 deaths were observed (15.5% of DARO and 19.1% of PBO patients). After unblinding at the primary analysis, 170 pts crossed over from PBO to DARO. DARO showed a statistically significant OS benefit corresponding to a 31% reduction in the risk of death compared with placebo. All other secondary endpoints were significantly prolonged by DARO (Table), regardless of the effect of crossover and subsequent therapies on survival benefit. Incidences of treatment-emergent adverse events (AEs) with ≥5% frequency were generally comparable between DARO and PBO, similar to the safety profile observed at the primary analysis. Incidences of AEs of interest (including falls, CNS effects, and hypertension) were not increased with DARO compared with PBO when adjusted for treatment exposure. AEs in the crossover group were consistent with those for the DARO treatment arm. Conclusions: DARO showed a statistically significant OS benefit for men with nmCRPC. In addition, DARO delayed onset of cancer-related symptoms and subsequent chemotherapy, compared with PBO. With extended follow-up, safety and tolerability were favorable and consistent with the primary ARAMIS analysis (Fizazi et al, N Engl J Med 2019;380:1235-46). Clinical trial information: NCT02200614 .[Table: see text]