tbuckley/cabot-search huggingface dataset:
Fecal immunochemical test followed by colonoscopy in opportunistic screening for colorectal neoplasm
Authors: Hanyue Ding, Dong Wu, Weixun Zhou, Jingnan Li
Journal: BMJ (2017)

Objective
To assess the fecal immunochemical test (FIT) followed by colonoscopy in opportunistic screenings for colorectal neoplasm.


Methods
Total 6 193 patients, who underwent opportunistic colorectal cancer (CRC) screening, were classified into four groups: 3 812 patients underwent direct colonoscopy (group 1), 1 244 patients received one FIT followed by colonoscopy (group 2), 341 patients received two FITs followed by colonoscopy (group 3), and 796 patients received three FITs followed by colonoscopy (group 4).


Results
Total 97 (1.6%) patients with CRC and 1 038 (16.8%) with colorectal adenoma were detected. The positive predictive value of 1, 2 and 3 positive tests out of three FITs for CRC were 4.53%, 5.62% and 8.94%, respectively, which was higher than that of direct colonoscopy (1.52%). One or more positive tests out of three FIT had the largest area under receiver operating characteristic curve (0.743). For colorectal adenoma, detection rate of direct colonoscopy (17 581.25/105) was higher than all FIT strategies (3 732.30/105-13 127.41/105).


Conclusions
Single or repeated FIT and colonoscopy have different screening utility. One or more positive tests out of three FIT followed by colonoscopy is preferred to screen CRC, and direct colonoscopy is better for detection of colorectal adenoma.


Key words: 
Colorectal neoplasms; Screening; Colonoscopy; Fecal occult blood test; Fecal immunochemical test
Causes of death in nodular lymphocyte predominant Hodgkin's lymphoma.
Authors: Anas M Saad, Ahmed Afifi, Mohamed Gad, Muneer J. Al-Husseini, Firas Baidoun, Talal Hilal
Journal: Journal of Clinical Oncology (2020)

e20016 Background: Nodular lymphocyte-predominant Hodgkin’s lymphoma (NLPHL) accounts for 5% of all cases of HL. The outcomes of patients with NLPHL is generally regarded as better than those with classical HL. However, causes of death (COD) of patients with NLPHL have not been previously described. Methods: The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program was used to identify all patients with NLPHL diagnosed between 1990 and 2015. Patient characteristics and disease stage, using the Ann-Arbor system, was extracted and tabulated. COD were identified and proportions were calculated for deaths within 5 years and after 5 years of diagnosis for patients with early and late stage NLPHL. Results: We identified 1,937 cases of NLPHL. The majority were younger than 65 years (86%), white (70%), male (67%), and diagnosed between 2001-2015 (85%), when rituximab was introduced. Of all cases, 1336 (69%) were classified as early stage. At a median follow-up of 91 months (IQR 41, 152) for early stage disease, and 73 months (IQR 30-123) for late stage disease, the median cancer-specific or overall survival were not reached. The estimated 5-year survival was 92% and 81% for early stage and late stage disease, respectively. Of all patients with early stage NLPHL, 186 (14%) died by the end of 2015, and 87 (46%) deaths occurred within 5 years of diagnosis. During the first 5 years after diagnosis, COD was NLPHL in 30 (35%). Beyond 5 years from diagnosis, NLPHL was the COD in 27% followed by other cancers (23%), and cardiovascular disease (18%). Of all patients with late stage NLPHL, 107 (21%) died, and 75 (70%) of deaths occurred within 5 years of diagnosis. During the first 5 years after diagnosis, COD was NLPHL in 44 (59%). Beyond 5 years from diagnosis, cardiovascular disease was the COD in 25%, followed by NLPHL (22%). Conclusions: The prognosis of NLPHL is excellent. Of all patients with NLPHL, those with advanced stage disease are more likely to die of their disease within 5 years of diagnosis. Patients with early and advanced stage disease beyond 5 years of diagnosis are more likely to die of causes other than NLPHL.
The neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios predict efficacy of CDK 4/6 inhibitors in women with hormone receptor-positive/HER2-negative advanced breast cancer.
Authors: Emma Zattarin, Chiara Fabbroni, Francesca Ligorio, Federico Nichetti, Riccardo Lobefaro, Licia Rivoltini, Giuseppe Capri, Giulia Valeria Bianchi, Filippo G. De Braud, Claudio Vernieri
Journal: Journal of Clinical Oncology (2020)

e13032 Background: Cyclin-dependent kinase (CDK) 4/6 inhibitors combined with endocrine therapies (ETs) are a mainstay of treatment for patients (pts) with hormone receptor-positive advanced breast cancer (HR+ aBC). Preclinical evidence indicates that their ability to stimulate antitumor immunity may crucially contribute to their anticancer activity. The neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) reflect systemic inflammation and immune system functional status and could be associated with CDK 4/6 inhibitor efficacy in pts with HR+ aBC. Methods: A retrospective, monocentric study was performed to investigate the association between NLR or PLR, as measured at baseline and after the first three treatment cycles, and progression free survival (PFS) in HR+ aBC pts treated with CDK 4/6 inhibitors. The thresholds for NLR and PLR were defined using the maximally selected rank statistics. Cox proportional hazard model was used to evaluate the impact of these parameters on PFS at univariate and multivariable analysis. Results: We evaluated a total number of 162 pts. Of them 142 were treated with palbociclib, 17 with ribociclib and 3 with abemaciclib plus ETs between January 2017 and December 2019 at our Institution. NLR and PLR at baseline were not associated with PFS. Conversely, high NLR ( &gt; 3) and high PLR ( &gt; 323.6) after three treatment cycles were associated with significantly lower PFS (p = 0.011 and p = 0.013, respectively). Multivariable analysis confirmed an independent association between high NLR or PLR and lower PFS (aHR 3.66, 95% CI 1.44-9.33, p = 0.007 and aHR 2.79, 95% CI 1.36-5.70, p = 0.005, respectively). Conclusions: To the best of our knowledge this is the first study to show a significant association between high NLR or PLR values and lower PFS in HR+ aBC pts treated with CDK 4/6 inhibitors. The association was not present with baseline values but only when NLR or PLR were measured after three treatment cycles, suggesting potential immunomodulatory activity of CDK 4/6 inhibitors.
Dexrazoxane and heart function among long-term childhood cancer survivors: A Children’s Oncology Group study.
Authors: Eric Jessen Chow, Sanjeev Aggarwal, David R Doody, Richard Aplenc, Saro Armenian, Kevin Scott Baker, Smita Bhatia, Nancy Blythe, Steven Colan, Louis S. Constine, David Robert Freyer, Lisa M. Kopp, Caroline Laverdiere, Wendy M. Leisenring, Nao Sasaki, Lynda M. Vrooman, Barbara Asselin, Cindy L. Schwartz, Steven E. Lipshultz
Journal: Journal of Clinical Oncology (2020)

10513 Background: Dexrazoxane (DRZ) has cardioprotective effects among doxorubicin (DOX) treated childhood cancer survivors up to 5 years after therapy. However, longer-term data are lacking. Methods: P9404, P9425, P9426, and DFCI 95-01 were randomized trials of acute lymphoblastic leukemia and Hodgkin lymphoma, where patients were randomly assigned to DOX±DRZ. P9754 enrolled osteosarcoma patients who all received DOX+DRZ. In all studies, DRZ was given as an intravenous bolus before DOX (10:1mg ratio). DOX doses ranged from 100-600 mg/m 2 across these 5 trials. A subset of COG institutions prospectively assessed cardiac function in long-term survivors from these trials, plus a matched group of osteosarcoma survivors treated with DOX alone. Echocardiograms (left ventricular [LV] Biplane ejection fraction [EF], shortening fraction [SF]) and blood biomarkers (b-type natriuretic peptides [BNP], N-terminal [NT] proBNP) were all analyzed centrally, with DRZ status masked. Lower LV function was defined as EF&lt;50% or SF&lt;30%. T-test, rank-sum, and multivariate regression adjusted for sex, cancer diagnosis age, current age, DOX dose, and chest radiotherapy were used to examine differences and associations by DRZ status. Results: Among 173 participants assessed (52% DRZ+; 54% male; mean DOX 294±96 mg/m 2 ) 17.6±2.4y since cancer diagnosis, DRZ+ participants were slightly younger (27.8 vs 29.6y, p=0.02), but baseline characteristics otherwise did not differ significantly by DRZ status. DRZ status was associated with higher FS (34.7±3.6% vs 33.4±4.3%, p=0.04) and EF (63.4±5.4% vs 61.4±5.5%, p=0.01), and lower BNP (median 10.4 pg/mL [IQR 6.0-18.0] vs 13.0 [IQR 6.0-28.2], p=0.03) and NT-proBNP (median 30.8 pg/mL [IQR 18.9-58.2] vs 47.1 [IQR 23.0-83.1], p&lt;0.01). In stratified analyses, the cardioprotective effects associated with DRZ tended to be more pronounced in females (vs males) and those who received DOX ≥300 mg/m 2 (vs &lt;300mg/m 2 ). Results from multivariate models were similar: DRZ was associated with higher SF (1.4% [95% CI 0.2, 2.6]) and EF (2.7% [95% CI 0.8, 4.6]), and reduced BNP (-4.0 pg/mL [95% CI -7.6, -0.4]) and NT-proBNP (-20.7 pg/mL [95% CI -33.5, -7.9]). Overall, DRZ was associated with a reduced risk of having lower LV function (odds ratio 0.27 [95% CI 0.08-0.96]). Conclusions: After &gt;17y, childhood cancer survivors treated with DOX+DRZ had better LV systolic function and less myocardial wall stress compared with those treated with DOX alone. DRZ may preferentially benefit females and those treated with greater DOX doses.
Nephrotoxicity due to immune checkpoint inhibitors in rural oncology.
Authors: Chady Abboud Leon
Journal: Journal of Clinical Oncology (2020)

e15084 Background: Case studies and retrospective chart reviews of health system data have demonstrated an increased risk of nephrotoxicity in patients receiving immune checkpoint inhibitors (CPIs) compared to the incidence of nephrotoxicity reported in clinical trials. The primary objective of this study is to determine the extent to which CPIs may induce nephrotoxicity in a real-world, rural population. The secondary objectives are to identify risk factors for renal dysfunction and describe real-world use of this relatively new class of medications. Methods: This represents a retrospective review of patients receiving at least one dose of a CPI at Marshfield Clinic Health System (MCHS) in Central Wisconsin from May 2013 to November 2019. Baseline serum creatinine, defined as the average of all serum creatinine values obtained within 6 months of the CPI start date, was compared to all serum creatinine measurements during CPI therapy and through 60 days after the last CPI dose. Acute kidney injury (AKI) was defined using the Kidney Disease Improving Global Outcomes definition. Patients developing an AKI of at least three day duration were further assessed to determine the likely cause of AKI. The incidence of potentially CPI-induced AKI was our primary outcome. Chi-square test will be used to compare incidence of AKI among different CPIs. A subdistribution hazard regression will be used to assess the association between the incidence of potentially CPI-induced AKI and patient characteristics (including comorbidities, type of cancer diagnosis, demographics, baseline ECOG score, CPI line in therapy, time lapse between diagnosis and CPI start, and concomitant nephrotoxic medications) while accounting for the competing risk of death. Results: A total of 922 patients received at least one dose of a CPI at MCHS during the study period. After applying exclusion criteria, a total of 920 patients were included in the analysis. The incidence of AKI of any duration and due to any cause was 29.5% (272 of 920 patients). Conclusions: The raw incidence of AKI in our patient population receiving CPIs is higher than previously published studies. However, our data are still being refined and research is in progress.
Utilization of imaging in pancreatic adenocarcinoma patients status post Whipple procedure.
Authors: Neal Shah, Ruchika Podury, Elias Kikano, Daniel Arnold Smith, Nikhil H. Ramaiya, Sree Harsha Tirumani
Journal: Journal of Clinical Oncology (2020)

e16725 Background: Pancreatic adenocarcinoma (PAC) remains the third leading cause of cancer death in the Western world. The 5-year survival of patients with PAC remains at 4%. Proper utilization of imaging to detect recurrence is necessary in patients who have undergone a Whipple procedure. Currently, Carbohydrate (CA) 19-9 is used for screening and is the only biomarker approved by the Food and Drug Administration (FDA). Sensitivity and specificity range from 79-81% and 82-90%. We intend to evaluate our single institute experience of imaging utilization, CA 19-9, and surgical specimen histopathologic features in the surveillance of PAC patients status post Whipple. Methods: Retrospective analysis of patients with a diagnosis of PAC who underwent imaging status post Whipple from 2008 - 2018 was completed. Cross-sectional imaging and clinical data was obtained from the electronic health record. Results: A total of 197 PAC patients status post Whipple were identified with mean age at diagnosis at 64.4 years and male to female ratio of 1.3. 85 patients were found to have died during treatment. The median survival for these patients was 68 years. Of the patients who died status post Whipple, postoperative CA 19-9 levels within 6 months of the procedure were elevated (p = 0.01). Patients who were found to have stage II to IV PAC at diagnosis were found to have a high CA 19-9 level within 6 months post-Whipple when compared to stage I patients (p &lt; 0.05). Patients who were found to have less than 5 surveillance CTs status post Whipple were found to have higher CA 19-9 levels within 6 months status post Whipple (p &lt; 0.01). There was no difference in number of CT scans between stages. Of those patients who died with stage I or II PAC at diagnosis, a large number were found to have less than 5 surveillance CT studies completed status post Whipple (p &lt; 0.05). Furthermore, a higher cancer stage at diagnosis correlated with worse pathologic differentiation of the cancer (p &lt; 0.001). Conclusions: Post Whipple CA 19-9 correlated with stage, recurrence, number of scans, and survival.
BRIGHTSTAR: A pilot trial of local consolidative therapy (LCT) with brigatinib in tyrosine kinase inhibitor (TKI)-naïve ALK-rearranged advanced NSCLC.
Authors: Yasir Elamin, Saumil Gandhi, Mara Antonoff, Frank Mott, Don Lynn Gibbons, Xiuning Le, Marcelo Vailati Negrao, Boris Sepesi, Jose A. Karam, Tina Cascone, Linghua Wang, George Blumenschein, Bonnie S. Glisson, Anne S. Tsao, John Heymach
Journal: Journal of Clinical Oncology (2020)

9624 Background: Approximately, 95% of patients who have an initial response to ALK-TKIs exhibit an incomplete response resulting in residual disease that enables the emergence of acquired resistance. Eliminating residual disease using LCT may delay resistance emergence and improve clinical outcomes. Methods: This is a single center investigator-initiated trial that assesses the safety, feasibility and efficacy of brigatinib with LCT. Eligible patients have TKI-naïve ALK rearranged advanced NSCLC with any number of metastases. Patients treated with brigatinib for an induction period of 8 weeks followed by LCT with radiation and/or surgery. Results: Between 12/2018 and 01/2020, 17 out of 24 planned patients were enrolled. Median age 55 (range 33-73). At study entry, 15 patients had polymetastatic disease ( &gt; 3 sites) while 2 had oligometastatic disease. As of February 1, 2020, 16 patients were evaluated for response and completed LCT while 1 patient remained on induction brigatinib. The disease control rate was 100% with an objective response rate of 94% (n = 15). Median follow up was 8 months (range 3-13) with no patients with disease progression to date. LCT used was radiation (n = 11), surgery (n = 3), surgery and radiation (n = 2). Among 5 patients who had surgery, 4 had lobectomy and mediastinal lymph node dissection (MLND), 1 had wedge resection with MLND, and 1 had adrenalectomy. Of these, 2 had complete pathological response and 1 had complete pathological response at the primary tumor. There were no grade ≥2 adverse events (AEs) related to LCT, including in 7 patients treated with concurrent brigatinib and radiation, and 6 patients treated with radiation while brigatinib was held. All patients continued brigatinib after LCT. Brigatinib-related severe AEs included grade 3: increased blood levels of creatine kinase, lipase, alanine aminotransferase, amylase (n = 1 each) and nausea (n = 1). One patient had grade 2 pneumonitis after 2 weeks of starting brigatinib, this resolved with steroids and brigatinib was resumed at a lower dose. Conclusions: Brigatinib with LCT is safe and feasible in patients with ALK-rearranged advanced NSCLC irrespective of number of metastatic sites. Brigatinib and LCT may be an effective therapeutic strategy in this subset of NSCLC patients. Clinical trial information: NCT03707938 .
非哺乳期化脓性乳腺炎23例致病菌及其耐药性分析
Authors: 杨颖, 胡崇珠, 刘文礼, 马宁, 王恩庆
Journal: BMJ (2008)

化脓性乳腺炎多见于哺乳期妇女,非哺乳期相对少见.金黄色葡萄球菌是哺乳期乳腺炎最主要的致病菌[1],非哺乳期乳腺炎病原菌及其耐药情况国内尚未见报道.2004年11月至2007年7月我院共收治非哺乳期化脓性乳腺炎23例,现将上述病例的细菌培养及药敏试验结果分析如下。
Preliminary safety and efficacy of GX-I7, a long-acting interleukin-7, in combination with pembrolizumab in patients with refractory or recurrent metastatic triple negative breast cancer (mTNBC): Dose escalation period of Phase Ib/II study (KEYNOTE-899).
Authors: Joohyuk Sohn, Kyong Hwa Park, Hee Kyung Ahn, Keun Seok Lee, Jee Hyun Kim, Sung-Bae Kim, Kyoung Eun Lee, Jee Hung Kim, Se Hwan Yang, Ngocdiep T. Le, Jiwon Kim, MinKyu Heo, Jung-Won Woo, Young Chul Sung, Young Hyuck Im
Journal: Journal of Clinical Oncology (2020)

1072 Background: Pembrolizumab monotherapy did not significantly improve OS as 2 nd and 3 rd -lines treatment for mTNBC compared to standard chemotherapy in phase III study (KEYNOTE-119) leading to high unmet needs of effective treatment. Recent studies showed that higher lymphocyte count is an independent factor which correlates with better response to checkpoint blockade in cancer patients. GX-I7, a long-acting interleukin-7, could potentially provide synergistic anti-tumor efficacy with pembrolizumab by increasing number of T cells both in tumor microenvironment (TME) and peripheral blood (PB). Methods: This is an open-label, phase Ib/II study in patients with refractory or recurrent TNBC who failed from standard chemotherapy in the metastatic setting, with ≤3 rd -lines of previous chemotherapy. The dose escalation phase adopted the 3+3 design. The GX-I7 doses were administered IM q9w or q12w, with or without cyclophosphamide pre-conditioning depending on the allocation, and in combination with pembrolizumab 200 mg IV q3w. The objectives were dose limiting toxicities (DLTs), safety, pharmacodynamic markers including lymphocyte increase and RP2D. Results: As of January 30, 2020, GX-I7 and pembrolizumab were exposed to 24 patients (median age 46.0 years [29-75], ECOG PS 1 [58.3%], median cycle no. 3 [1-9]). Treatment was discontinued in 13 (54.2%), majority due to PD and 11 patients are ongoing. No DLTs were reported in all dose groups. Treatment related AEs occurred in 91.7% of patients with grade 1-2 and 9.1% with grade 3 (no grade 4). Common AEs were injection site reaction (39.0%) and fever (13.0%), which were easily managed. Grade 3 toxicity were AST/ALT elevation and infusion related reaction, reported from 1 patient each (4.2%). GX-I7 induced dose-dependent lymphocyte proliferation in PB, with approximately 4-folds increase in high doses. 17 patients were evaluable; confirmed objective responses from ongoing patients included one partial response (5.9%), 2 stable disease (11.8%) and 1 durable unconfirmed PD (5.9%). Conclusions: GX-I7 in combination with pembrolizumab was well tolerated, with no DLTs reported. There was no apparent increase of immune-related AEs with the addition of GX-I7. Pharmacodynamics data support proof of mechanism and it warrants further clinical studies. Clinical trial information: NCT03752723 .
Design and application of intelligent community chronic disease management information system centered on patients
Authors: Hongyan Jia, Xiaoling Guo, Caiying Ge, Li Wang, Xuejuan Wei, Min Kong
Journal: BMJ (2015)

To implement the effective docking and optimization of a new community comprehensive management information system and cardiocerebrovascular disease-related auxiliary system for a community-based information platform for intelligent chronic disease management. The cooperation of community team and a distinct division of labors were enforced according to standard operating procedures. This mode of patient-centered medical home(PCMH) could offer scientific and effective management, promote the rational classification of medical and two-way referral systems and improve service efficiency and management capabilities for the goals of achieving a reasonable allocation of medical resources and saving medical costs.


Key words: 
Disease management, chronic disease; Hospital information systems
The Clinical Challenge of Clonal Hematopoiesis, a Newly Recognized Cardiovascular Risk Factor
Authors: Robert Sidlow, Amy E. Lin, Dipti Gupta, Kelly L. Bolton, David P. Steensma, Ross L. Levine, Benjamin L. Ebert, Peter Libby
Journal: JAMA Cardiology (2020)

Despite current standards of cardiovascular care, a considerable residual burden of risk remains in both primary and secondary prevention. Clonal hematopoiesis of indeterminate potential (CHIP) has recently emerged as a common, potent, age-associated, independent risk factor for myocardial infarction, stroke, heart failure events, and survival following percutaneous aortic valve intervention. The presence of CHIP results from the acquisition of somatic mutations in a small number of leukemia driver genes found in bone marrow stem cells, leading to the expansion of leukocytes clones in peripheral blood. The association between CHIP and cardiovascular disease likely involves activation of the inflammasome pathway. More common DNA sequencing identifies individuals with CHIP who then seek advice regarding management of their cardiovascular risk.Using clinical vignettes based on real encounters, we highlight some of the diverse presentations of CHIP, ranging from incidental identification to that detected during cancer care, that have brought patients to the attention of cardiovascular practitioners. We illustrate how we have applied a consensus-based approach to the evaluation and management of cardiovascular risk in specific patients with CHIP. Since we currently lack evidence to guide the management of these individuals, we must rely on expert opinion while awaiting data to furnish a firmer foundation for our recommendations.These vignettes illustrate that the management of CHIP should involve an individualized plan based on features such as comorbidities, life expectancy, and other traditional cardiovascular risk factors. Because individuals with CHIP will increasingly seek advice from cardiovascular specialists regarding management, these examples provide a template for approaches based on a multidisciplinary perspective. The current need for reliance on expert opinion illustrates a great need for further investigation into the management of this newly recognized contributor to residual cardiovascular risk, both in patients who are apparently well and those with established cardiovascular or malignant disease.