tbuckley/cabot-search huggingface dataset:
Association Between Off-site Central Monitoring Using Standardized Cardiac Telemetry and Clinical Outcomes Among Non–Critically Ill Patients
Authors: Daniel J. Cantillon, Molly Loy, Alicia Burkle, Shannon Pengel, Deborah Brosovich, Aaron Hamilton, Umesh N. Khot, Bruce D. Lindsay
Journal: JAMA (2016)

<h3>Importance</h3> Telemetry alarms involving traditional on-site monitoring rarely alter management and often miss serious events, sometimes resulting in death. Poor patient selection contributes to a high alarm volume with low clinical yield. <h3>Objective</h3> To evaluate outcomes associated with an off-site central monitoring unit (CMU) applying standardized cardiac telemetry indications using electronic order entry. <h3>Design, Setting, and Participants</h3> All non–intensive care unit (ICU) patients at Cleveland Clinic and 3 regional hospitals over 13 months between March 4, 2014, and April 4, 2015. <h3>Exposures</h3> An off-site CMU applied standardized cardiac telemetry when ordered for standard indications, such as for known or suspected tachyarrhythmias or bradyarrhythmias. <h3>Main Outcomes and Measures</h3> CMU detection and notification of rhythm/rate alarms occurring 1 hour or less prior to emergency response team (ERT) activation, direct CMU-to-ERT notification outcomes, total telemetry census, and cardiopulmonary arrests in comparison with the previous 13 months. <h3>Results</h3> The CMU received electronic telemetry orders for 99 048 patients (main campus, 72 199 [73%]) and provided 410 534 notifications (48% arrhythmia/hemodynamic) among 61 nursing units. ERT activation occurred among 3243 patients, including 979 patients (30%) with rhythm/rate changes occurring 1 hour or less prior to the ERT activation. The CMU detected and provided accurate notification for 772 (79%) of those events. In addition, the CMU provided discretionary direct ERT notification for 105 patients (ventricular tachycardia, n = 44; pause/asystole, n = 36; polymorphic ventricular tachycardia/ventricular fibrillation, n = 14; other, n = 11), including advance warning of 27 cardiopulmonary arrest events (26%) for which return of circulation was achieved in 25 patients (93%). Telemetry standardization was associated with a mean 15.5% weekly census reduction in the number of non-ICU monitored patients per week when compared with the prior 13-month period (580 vs 670 patients; mean difference, −90 patients [95% CI, −82 to −99];<i>P</i> &lt; .001). The number of cardiopulmonary arrests was 126 in the 13 months preintervention and 122 postintervention. <h3>Conclusions and Relevance</h3> Among non–critically ill patients, use of standardized cardiac telemetry with an off-site central monitoring unit was associated with detection and notification of cardiac rhythm and rate changes within 1 hour prior to the majority of ERT activations, and also with a reduction in the census of monitored patients, without an increase in cardiopulmonary arrest events.
Abstract 4304: Prevalence and triggers of drug-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in a cancer patient cohort
Authors: Nancy K. Gillis, Gillian C. Bell, Howard L. McLeod, Amy J. Brandt
Journal: Cancer Research (2016)

Abstract SJS and TEN are extremely rare (approximately 2-7 cases per million per year) hypersensitivity reactions most commonly attributed to medications. The life-threatening nature of SJS/TEN necessitates early diagnosis and immediate identification and withdrawal of causative agents. Some of the most commonly associated culprits include sulfonamide antibiotics, aromatic anticonvulsants (phenytoin, carbamazepine, lamotrigine), -oxicam NSAIDs (e.g., meloxicam), allopurinol, and nevirapine. Individual case reports of SJS/TEN have been associated with anti-cancer agents, but a comprehensive assessment has not been performed. A large-scale retrospective analysis of the prevalence of SJS/TEN in cancer patients treated at Moffitt Cancer Center (MCC) between Jan 1, 2002 - Dec 31, 2014 was conducted. A total of 104,917 cancer patients were screened for SJS/TEN-related ICD-9 codes in the MCC health research informatics database. SJS/TEN diagnoses were identified in 121 patients. Manual chart review of physician, dermatology, and pathology notes confirmed SJS/TEN in 47 patients (in-patient + historical) and possible SJS/TEN in an additional 17 patients, corresponding to an overall prevalence of 0.06%. Confirmed in-patient cases of SJS/TEN were more common in hematologic malignancies compared to solid tumors (n = 12 vs. n = 7, respectively). Notably, 5 of the 19 (26.3%) confirmed cases were observed in patients with acute myeloid leukemia. Physician-reported culprits for SJS/TEN diagnoses included antibiotics, immunomodulators, anticonvulsants, and anti-cancer agents. The observed prevalence of SJS/TEN was higher in cancer patients than previous reports from the general USA population. There were 19 confirmed in-patient diagnoses of SJS/TEN and an additional 45 historical and possible cases of SJS/TEN in 104,917 cancer patients, corresponding to an overall prevalence of 0.018% to 0.06%, an approximately 90-fold increase when compared to the general population. Possible explanations for increased risk in cancer patients include increased exposure to culprit medications, cancer disease process, immunocompromised state, or synergy between risk factors. A thorough understanding of the factors that increase risk to SJS/TEN in cancer patients is critical to facilitate culprit withdrawal and maximize patient outcomes and survival. Citation Format: Nancy K. Gillis, Gillian C. Bell, Howard L. McLeod, Amy J. Brandt. Prevalence and triggers of drug-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in a cancer patient cohort. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4304.
A Tumor Suppressor microRNA Defines the Leukemic Hierarchy in Acute Myeloid Leukemia
Authors: Edith Schneider, Anna Staffas, Linda Roehner, Christian Buske, Lars Bullinger, Michael Heuser, Hartmut Döhner, Konstanze Döhner, R. Keith Humphries, Arefeh Rouhi, Lars Palmqvist, Florian Kuchenbauer
Journal: Blood (2015)
Outcomes in metastatic pancreatic adenocarcinoma (MPAC) patients treated with FOLFIRINOX (FFX)/FOLFOX(FX) and gemcitabine + nab-paclitaxel (NabG).
Authors: Shannon Leah Schmidt, Vipal Durkal, Shinoj Pattali Jayavalsan, James P. Thomas, Paul S. Ritch, Beth Erickson, Kathleen K. Christians, Susan Tsai, Douglas B. Evans, Ben George
Journal: Journal of Clinical Oncology (2016)

397 Background: Standard front line (FL) chemotherapy regimens for MPAC include FOLFIRINOX (FFX)/FOLFOX(FX) and Nab-paclitaxel plus Gemcitabine (NabG). Outcome data in patients treated with both FFX/FX and NabG has not been well characterized. We retrospectively reviewed our single institution experience in MPAC patients treated with FFX/FX and NabG in either sequence. Methods: All MPAC patients treated with FFX/FX or NabG, in either sequence, from 1/1/11 to 12/31/14 at the Froedtert and Medical College of Wisconsin (MCW) Clinical Cancer Center were identified and their charts reviewed. This study was approved by the Froedtert &amp; MCW Institutional Review Board. Results: Among the 64 patients reviewed, median age at diagnosis was 62 years, 64.1% were male and 95.3% were Caucasian. Median Ca19-9 and CEA at diagnosis were 855 and 10.4 respectively. Liver, lung and peritoneal metastases were appreciated in 87.5%, 20.3% and 35.9% of patients. 37/64 (57.8%) patients received second line (SL) therapy. Response Rate (RR) with FFX/FX and NabG in both FL and SL therapy are summarized in the Table. The median Progression Free Survival (PFS) with FL therapy was 3.7 months and 3.5 months with SL therapy. Median overall survival (OS) of the entire cohort was 8.7 months. In patients who received 2 lines of therapy the median OS was 12.1 months. Median OS in patients who received only one line of therapy was 4.1 months. Conclusions: In patients with MPAC, sequential therapy with FFX/FX and NabG is both feasible and effective in either sequence. RR and DCR with these regimens, while modest, are acceptable in the SL setting. Patients who received two lines of therapy have a substantially better OS than patients who receive one line of therapy, suggesting a more favorable tumor biology in the former population. [Table: see text]
Use of a prognostic (prog) gene index and nodal status to identify a subset of stage II and III colon cancer patients (pts) who may not need oxaliplatin (ox)-containing adjuvant chemotherapy.
Authors: K. L. Pogue-Geile, G. A. Yothers, P. Gavin, D. Fumagalli, C. Kim, L. H. Colangelo, C. E. Geyer, M. J. O'Connell, N. Wolmark, S. Paik
Journal: Journal of Clinical Oncology (2010)

3516 Background: NSABP C-07 showed the superiority of adding ox to 5-FU/LV, but this benefit is associated with significant toxicity. A prog or predictive test is needed to identify pts who may not need ox in addition to 5-FU/LV. Methods: The C-07 cohort was divided into assay development (dev) and assay validation (val) sets of equal sizes.This report considers the dev set (N=956). RNA extracted from formalin-fixed, paraffin-embedded blocks was assayed by microarray gene expression profiling. The dev cohort was divided into equal-sized training and val subsets. Supervised principal component analysis (BRB Array Tools) was done on the training subset (N=478) to develop a prog index from 33 genes significant at 0.0001. Results: Pts in the val subset (N=478) were classified hi or lo risk based on the median value of the prog index from the training set. Risk class was sig associated with time to recurrence (TTR) (N=478, HR=2.43,95%CI:1.69-3.49, p<0.0001). In the val set, 82.6% of lo-risk pts were recurrence-free at 5 yr (95% CI 78.1-87.4) vs. 64.3% with hi risk (95% CI 58.2-71.2). Subsequent analyses use the full assay dev cohort of 956 pts.Ox benefit did not sig interact with risk classification (p=0.21), but the difference in absolute risk of recurrence is so large between risk groups that the relative benefit of ox for pts in the lo-risk subset may not be large enough to offset the risks of trtmt. In multivariate modeling, risk class (p<0.0001) and node category (p<0.0001) were independent predictors of TTR (Table). Conclusions: A gene expression-based prog index was an independent predictor of TTR. Lo-risk pts may not need to add ox to 5-FU/LV. A nanostring platform will be used to transform this prog index into a clinical assay that will be validated using the assay val cohort protected from the assay dev steps. Funded in part by a grant from the PA Dept of Health, which disclaims responsibility for analyses, interpretations, conclusions. Risk class Node category N Recurrences % Recurrence free at 5 yr Lo Neg 12+ examined 119 6 94.6 ″ Neg < 12 “ 66 3 95.1 ″ 1-3 pos 219 33 84.5 ″ 4+ pos 95 30 67.9 Hi Neg 12+ “ 50 9 81.6 ″ Neg < 12 “ 53 14 73.1 ″ 1-3 pos 224 78 64.0 ″ 4+ pos 130 80 36.4 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GHI GlaxoSmithKline
Hormone-Replacement Therapy for Melanocyte-Stimulating Hormone Deficiency
Authors: Marc L. Reitman
Journal: New England Journal of Medicine (2016)

The first law of endocrine disease treatment is that an absent hormone should be replaced. As they report in this issue of the Journal, Kühnen et al.1 successfully applied this principle to two adult patients with genetic proopiomelanocortin deficiency, and both patients had impressive hunger reduction and weight loss as well as improved insulin sensitivity.Proopiomelanocortin is a prohormone that is cleaved in different cells to produce multiple peptide ligands that act primarily on the five melanocortin receptors.2 The pituitary corticotroph product, adrenocorticotropic hormone, stimulates the adrenal gland through the melanocortin-2 receptor (MC2R). Clinically, proopiomelanocortin deficiency is dominated by a . . .
Role of STAT1 Expression during Graft-Versus-Host Disease (GVHD) in the Gastrointestinal Tract: Association with Lamina Propria Cell Infiltration and Tissue Cytokine/Chemokine Expression.
Authors: Judy A. Ziegler, Anna Lokshin, Antonia R. Sepulveda, Ahmed Bedeir, Suzanne Lentzsch, Markus Y. Mapara
Journal: Blood (2006)
Comparison of cisplatin-based neoadjuvant chemotherapy for bladder cancer in elderly versus younger patients.
Authors: Caroline Shuet Yiu Chau, Matthew James Wheater, Thomas R. Geldart, Simon J. Crabb
Journal: Journal of Clinical Oncology (2014)

e15502 Background: Bladder cancer is a disease of the elderly, with a peak incidence between 75 – 79 years in the UK. Non-metastatic muscle invasive bladder cancer is potentially curable with radical cystectomy or radiotherapy. The addition of neoadjuvant cisplatin based chemotherapy provides an absolute overall survival benefit of 5-6%. Older patients may potentially receive less intense, and possibly inferior, therapy primarily due to concerns that they are more likely to develop treatment related toxicities. We hypothesised that cisplatin based neoadjuvant chemotherapy in elderly patients would be feasible if appropriately selected. Methods: An ethically approved, single institution, retrospective analysis of patients with T2-4a N0 M0 transitional cell carcinoma (TCC) of the bladder treated with cisplatin based neoadjuvant chemotherapy between 2005 and 2011. Data collection: case note and database review. Elderly cohort: aged ≥70 years. Outcome measures: overall survival (OS), relapse free survival (RFS). Univariate analyses of survival outcomes were generated using the Kaplan-Meier method and differences analysed by log rank tests. Results: 83 patients identified. Median age 68 (range 48-80), 33 (40%) aged ≥70. Patient characteristics were well matched between the two groups. 48.5% of ≥70 and 60% of <70 had subsequent cystectomy (p=0.339). 31.3% of ≥70 and 40% of <70 who were cystectomised achieved pathological complete response. 63.6% of ≥70 and 60% of <70 remain relapse free (p=0.906). Distant and local relapse rates were similar; distant relapse 24.2% of ≥70 and 28% of <70, local relapse (post radiotherapy patients) 12.2% of ≥70 and 12.0% of <70. OS at 3 years was 65.8% ≥70 and 63.2% (p=0.653). Chemotherapy was completed by 78.8% ≥70 years and 82.0% <70 (p=0.885). Toxicity was comparable in elderly and younger patients. Conclusions: Appropriately selected elderly patients (≥70 years) with muscle invasive TCC of the bladder treated with neoadjuvant cisplatin based chemotherapy prior to radical surgery or radiotherapy have comparable clinical outcomes to younger patients. Our findings support prospective studies evaluating the optimum and individualised management of this elderly cohort.
Abstract 4604: Activities of <i>in vitro</i> prepared recombinant wnt inhibitory factor-1 (Wif-1)
Authors: Duaa A. Babaer, Xiaofei Wang
Journal: Cancer Research (2016)

Abstract Wnt Inhibitory Factor-1 (Wif-1) is a secreted modular protein that inhibits the activities of Wnt signaling pathway. The latter is involved in many aspects of cancer and embryonic development. Many studies have shown that reduced WIF-1 expression is associated with the development of cancer. Since WIF-1 acts in extracellular space, it is possible to use in vitro expressed WIF-1 as a therapeutic agent for cancer treatment. We tested whether in vitro expressed recombinant WIF-1 could elicit inhibitory effects on Wnt pathway in 3T3 cells by examining the expression of insulin-like growth factor II (Igf2), Wnt1 inducible signaling pathway protein 2 (Wisp2), (C/EBPδ), and peroxisome proliferator-activated receptor γ (PPARγ) which has been implicated as a suppressor in numerous cancer types including human breast, lung, and colon cancer. 3T3 cells were treated with 0, 1, 5 and 20 ng/ml of recombinant mouse Wif-1 protein. Total RNA was isolated after 24-48 hours of treatment. The levels of Igf2, Wisp2, C/EBPδ, and PPARγ mRNA were analyzed with reverse transcription quantitative polymerase chain reaction. Results are being analyzed to determine whether the in vitro expressed recombinant Wif-1 protein can modulate the expression of these genes and regulate cancer to have a significant inclusion in the field of cancer biology. Citation Format: Duaa A. Babaer, Xiaofei Wang. Activities of in vitro prepared recombinant wnt inhibitory factor-1 (Wif-1). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4604.
Correlation between tumor-free axillary lymph node morphology and clinicopathologic features in invasive breast cancer.
Authors: Tae-Kyung Yoo, Hyeong-Gon Moon, Min Kyoon Kim, Eunshin Lee, Han-Byoel Lee, Young Joon Kang, Yun Kyeong Kim, Wonshik Han, Woo Kyung Moon, Dong Young Noh
Journal: Journal of Clinical Oncology (2015)

e12059 Background: Enlargement of the cortex of a lymph node is known to indicate an early change of metastasis and this has been suggested as a criterion for differentiation of suspicious lymph nodes in breast cancer. Despite the high positive predictive value of these classifications, some tumor-free lymph nodes present with thick cortex or loss of fatty hilum. The purpose of this study is to examine the relationship between preoperative sonographic lymph node classification and clinicopathologic features in breast cancer with no axillary lymph node metastasis. Methods: Patients who received primary surgery for invasive breast cancer between November 2005 and December 2009 were retrospectively reviewed. Preoperative sonographic classification of axillary lymph nodes (ALN sono grade) was performed for all patients, one day before surgery. Maximum thickness of cortex and appearance of fatty hilum were evaluated and classified: grade 1, ≤ 1.5mm; grade 2, > 1.5mm, ≤ 2.5mm; grade 3, > 2.5mm, ≤ 3.5mm; grade 4, > 3.5mm, intact fatty hilum; grade 5, > 3.5mm, loss of fatty hilum. This classification has been previously validated (Cho et al, Am J Roentgenol, 2009). Results: A total of 1,827 patients were proven of having no axillary lymph node metastasis. Younger age, larger tumor size, high nuclear grade, high histologic grade, strong Ki-67 expression, hormone receptor negative and triple-negative breast cancer were all significantly related to having ALN sono grade ≥ 3. Patients with ALN sono grade ≥ 3 presented with significantly worse disease-free survival compared to patients with benign looking axillary lymph nodes. But after adjusting for prognostic factors (age, tumor size, histologic grade, Ki-67 expression and hormone receptor status) there was no survival difference. Conclusions: Thick cortex or loss of fatty hilum in tumor-free axillary lymph nodes is related to adverse clinicopathologic features in primary invasive breast cancer. The immunologic configuration of these suspicious-looking tumor-free lymph nodes will be investigated in future studies.
Long-term follow-up of exceptional responders on the phase II trial of weekly bortezomib and rituximab in untreated and relapsed patients with waldenstrom's macroglobulinemia.
Authors: Joseph M. Cappuccio, Irene M. Ghobrial, Jorge J. Castillo, Steven P. Treon, Jeffrey Matous, Patrick M. Henrick, Aaron M. Caola, Emily Lai
Journal: Journal of Clinical Oncology (2016)

8065 Background: This follow-up study aimed to update the progression-free survival (PFS) and identify responder subgroups in the phase II trial of Bortezomib and Rituximab in patients with Waldenstrom Macroglobulinemia (WM). Methods: This study contained Up-front and relapsed/refractory (R/R) patients. PFS was defined by the time between therapy initiation and progression, death or last follow-up. Results: Twenty-six up-front patients were treated. Overall response (ORR) was 100%; 8% complete response (CR), 58% partial response (PR) and 35% minor response (mR). Median PFS was 37 months. 5-year PFS and OS rates were 41% and 94%. Best responders were defined as > 36 months without progression since therapy initiation, and comprised 42% of the cohort (n = 11/26). Best responders were less likely to have IgM > 4000 mg/dL at baseline (36% vs. 80%, p = 0.03). Exceptional responders were defined as > 60 months without progression since therapy initiation, and comprised 19% of the cohort (n = 5/26). Exceptional responders were also less likely to have IgM > 4000 mg/dL (20% vs. 71%; p = 0.05). Thirty-seven R/R patients were treated. ORR was 81%; 5% CR, 46% PR, and 11% mR. Median PFS was 19 months with 3-year PFS of 22%. Median OS has not yet been reached, and 5-year OS was 65%. Best responders were defined as > 18 months without progression since therapy initiation, and comprised 43% of the cohort (n = 16/37). Best responders were less likely to present with hemoglobin (HgB) < 11.5 g/dL at baseline (33% vs. 71%; p = 0.03). Exceptional responders were defined as > 36 months without progression since therapy initiation, and comprised 14% of the cohort (n = 5/37). Exceptional responders were less likely to have beta-2-microglobulin (B2M) > 3 mg/dL at baseline (0% vs. 61%; p = 0.04). Conclusions: The combination of weekly bortezomib and rituximab showed significant activity in patients with untreated & R/R WM. Approximately 15-20% of those patients experienced prolonged PFS beyond 60 or 36 months in both respective populations. IgM, HgB or B2M may identify exceptional responders without the need for maintenance rituximab. Still, better predictors of long-term response are needed. Clinical trial information: NCT00422799.
An unusual case of acute kidney injury after colonoscopy
Authors: Nobuhiro Hashimoto, Isao Matsui, Tomoko Namba, Tatsufumi Oka, Daisuke Mori, Yusuke Sakaguchi, Masayuki Mizui, Takayuki Hamano, Yoshitsugu Takabatake, Yoshitaka Isaka
Journal: Kidney International (2016)
Comprehensive Metabolomic Characterization of Coronary Artery Diseases
Authors: Yong Fan, Yong Li, Yan Chen, Yi-Jing Zhao, Li-Wei Liu, Jin Li, Shi-Lei Wang, Raphael N. Alolga, Yin Yin, Xiang-Ming Wang, Dong-Sheng Zhao, Jian-Hua Shen, Fan-Qi Meng, Xin Zhou, Hao Xu, Guo-Ping He, Mao-De Lai, Ping Li, Wei Zhu, Lian-Wen Qi
Journal: Journal of the American College of Cardiology (2016)
Grover’s-like drug eruption in a patient with metastatic melanoma under ipilimumab therapy
Authors: Viktor H. Koelzer, Tobias Buser, Niels Willi, Sacha I. Rothschild, Andreas Wicki, Peter Schiller, Gieri Cathomas, Alfred Zippelius, Kirsten D. Mertz
Journal: Journal for ImmunoTherapy of Cancer (2016)

Dermatologic toxicity is an important adverse effect of immune checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death 1 receptor (PD-1) or PD ligand 1 (PD-L1). Skin toxicity most commonly includes a maculopapular erythematous rash and pruritus. Rarely life threatening complications such as Steven's Johnson syndrome or toxic epidermal necrolysis may occur.Here we report the uncommon event of a drug-induced transient acantholytic dermatosis (Grover's disease) in a 73-year-old Caucasian male treated with ipilimumab for metastatic melanoma. Five weeks after initiation of therapy, the patient developed a widespread polymorphic papulovesicular dermatosis on the trunk and proximal extremities with intense pruritus. Skin biopsy showed acantholytic dyskeratosis with interface dermatitis consistent with a Grover's-like drug eruption.These findings should raise awareness for uncommon immune-related dermatological toxicities of immunomodulatory antibodies targeting the CTLA-4 signaling axis. We recommend biopsies of unexpected skin lesions to rapidly identify dermatological adverse events of immune checkpoint inhibitors.
A Phase I Trial of AT9283, a Multitargeted Kinase Inhibitor, in Patients with Refractory Hematological Malignancies.
Authors: Farhad Ravandi, James Foran, Srdan Verstovsek, Jorge Cortes, William Wierda, Patricia Boone, Gautam Borthakur, Trish Sweeney, Hagop Kantarjian
Journal: Blood (2007)