tbuckley/cabot-search huggingface dataset:
A phase III trial comparing R-CHOP 14 and R-CHOP 21 for the treatment of patients with newly diagnosed diffuse large B-cell non-Hodgkin's lymphoma
Authors: D. Cunningham, P. Smith, P. Mouncey, W. Qian, C. Pocock, K. M. Ardeshna, J. Radford, J. Davies, A. McMillan, D. Linch
Journal: Journal of Clinical Oncology (2009)

8506 Background: The addition of rituximab to standard therapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP21) has resulted in improved survival outcomes in the treatment of diffuse large B-cell non-Hodgkin's lymphoma (DLBC NHL). In addition, the administration of CHOP as a 14 day cycle (CHOP14) has shown benefit over standard CHOP21 chemotherapy. This randomised study was designed to evaluate the toxicity and survival outcomes achieved with the addition of rituximab to CHOP14 (R-CHOP14), as compared to standard therapy (R-CHOP21) in newly diagnosed DLBC NHL. Methods: Patients were randomised to receive either eight cycles of standard R-CHOP21 or six cycles of R-CHOP14 (+ G-CSF) with two additional cycles of single agent rituximab. Randomisation was stratified by age (≤60 vs &gt;60), WHO performance status (0–1 vs 2) and LDH level (normal vs raised). The primary endpoint is overall survival. The study was powered to detect an improvement in 2-year survival in the R-CHOP14 arm of 8% (70% to 78%) with 5% significance and 90% power (2-sided). Results: Recruitment is complete with 1080 patients randomised. Patient characteristics in the R-CHOP21 and R-CHOP14 arms are; IPI score of ≥4 17%:15%, stage III/IV disease 63%:62%, B symptoms 44%:47%, bulk disease 51%:48%. Median age is 61 years in both arms. 82% of patients in the R-CHOP21 arm completed study therapy as compared to 89% in the R-CHOP14 arm. Reported grade III/IV toxicities in the R-CHOP21 and R-CHOP14 arms are; neutropenia 57%:31%, thrombocytopenia 5%:9%, Infection 22%:17%, cardiac 1%:2%, nausea &amp; vomiting 8%:8%, mucositis 2%:3%. The radiological complete response rate (CR/CRu) is 47% in both treatment arms. With a median follow-up 14 months 805 patients remain alive. Conclusions: Results indicate that R-CHOP14 can be delivered as effectively as R-CHOP21 with comparable levels of acute toxicity. Final analysis will be performed when 330 deaths have occurred. No significant financial relationships to disclose.
Sixty seconds on . . . mindfulness
Authors: Nigel Hawkes
Journal: BMJ (2016)

Try mindfulness. It’s the antidote to stress, distilled from the wisdom of ancient Buddhism and brought bang up to date to ease the travails of the modern world.

It’s easy to scoff. But plenty of people find it helpful, and it’s inching towards making the transition from pop psychology to clinical acceptance. It may be a …
Gab1 adaptor protein acts as a gatekeeper to balance hepatocyte death and proliferation during acetaminophen‐induced liver injury in mice
Authors: Kunimaro Furuta, Yuichi Yoshida, Satoshi Ogura, Tomohide Kurahashi, Takashi Kizu, Shinichiro Maeda, Mayumi Egawa, Norihiro Chatani, Keigo Nishida, Yoshikazu Nakaoka, Shinichi Kiso, Yoshihiro Kamada, Tetsuo Takehara
Journal: Hepatology (2015)

Acetaminophen (APAP) overdose is the leading cause of drug‐induced acute liver failure. In APAP‐induced acute liver failure, hepatocyte death and subsequent liver regeneration determines the prognosis of patients, making it necessary to identify suitable therapeutic targets based on detailed molecular mechanisms. Grb2‐associated binder 1 (Gab1) adaptor protein plays a crucial role in transmitting signals from growth factor and cytokine receptors to downstream effectors. In this study, we hypothesized that Gab1 is involved in APAP‐induced acute liver failure. Hepatocyte‐specific Gab1 conditional knockout ( Gab1 CKO) and control mice were treated with 250 mg/kg of APAP. After APAP treatment, Gab1 CKO mice had significantly higher mortality and elevated serum alanine aminotransferase levels compared to control mice. Gab1 CKO mice had increased hepatocyte death and increased serum levels of high mobility group box 1, a marker of hepatocyte necrosis. In addition, Gab1 CKO mice had reduced hepatocyte proliferation. The enhanced hepatotoxicity in Gab1 CKO mice was associated with increased activation of stress‐related c‐Jun N‐terminal kinase (JNK) and reduced activation of extracellular signal‐regulated kinase and AKT. Furthermore, Gab1 CKO mice showed enhanced mitochondrial translocation of JNK accompanied by an increase in the release of mitochondrial enzymes into the cytosol, which is indicative of increased mitochondrial dysfunction and subsequent nuclear DNA fragmentation. Finally, in vitro experiments showed that Gab1‐deficient hepatocytes were more susceptible to APAP‐induced mitochondrial dysfunction and cell death, suggesting that hepatocyte Gab1 is a direct target of APAP‐induced hepatotoxicity. Conclusion: Our current data demonstrate that hepatocyte Gab1 plays a critical role in controlling the balance between hepatocyte death and compensatory hepatocyte proliferation during APAP‐induced liver injury. (H epatology 2016;63:1340–1355)
Is there a need for multiple measures in assessing quality of life in oncology?
Authors: I. P. Farmer, L. F. Johnson, D. Gupta, J. F. Grutsch, J. Granick, P. Williams, T. Wodek, C. G. Lis
Journal: Journal of Clinical Oncology (2005)

8098 Background: The European Organization for Research Treatment of Cancer - Quality of Life Questionnaire (EORTC) and Ferrans & Powers Quality of Life Index (QLI) are the two most widely used instruments to measure quality of life (QoL) in oncology. Previously we reported the concordance of these instruments in a cohort of newly admitted cancer patients at our treating center in Zion, IL. The purpose of this investigation was to evaluate if we could obtain similar results at our treating cancer in Tulsa, OK. Methods: A survey of 141 adult cancer patients presenting for treatment at Cancer Treatment Centers of America at Southwestern Regional Medical Center was completed between 01/04 and 05/04. QoL was measured using EORTC and QLI. EORTC incorporates 5 functional scales (physical, role, cognition, emotional, and social), 9 symptom scales (fatigue, pain, and nausea/vomiting, dyspnea, insomnia, loss of appetite, constipation, diarrhea, financial problems), and a global QoL scale. QLI measures overall QoL as well as QoL in 4 major scales: health/physical, social/economic, psychological/spiritual, and family. The correlations between different scales of EORTC and QLI were evaluated using the Pearson’s correlation coefficient (r). Results: Of 141 patients, 72 (51%) were males and 69 (49%) females with a median age of 56 years (range 22 - 84). 82 (58%) patients had failed prior treatment while 59 (42%) were newly diagnosed. 34 (24%) had breast ca, 26 (18.4%) lung ca, 25 (17.7%) prostate ca, 12 (8.5%) colorectal ca, while 44 (31%) had a variety of other cancers. 74 patients (52.5%) had stage IV disease. Correlations between the corresponding scales of EORTC and QLI were low (r = 0.1 - 0.4; p<0.05), with the exception of QLI health scale, which was strongly correlated with all EORTC functional scales (r = 0.4 - 0.8; p<0.05). Conclusions: We found that EORTC and QLI measure different aspects of QoL, with the only areas of strong correlation between QLI health scale and EORTC functional scales. This study confirms our previous finding that both instruments provide information that would otherwise not be captured by a single instrument. No significant financial relationships to disclose.
Abstract 14962: Weekend versus Weekday Admission and Morality from Acute Coronary Syndrome
Authors: Mahdi Khoshchehreh, Elliott Groves, DavidM. Tehrani, Shaista Malik
Journal: Circulation (2014)

Introduction: ACS is a common condition requiring urgent diagnosis and intervention. Previous smaller studies show poor outcomes for time-sensitive medical conditions during weekend admissions, however whether these associations persist is not known. Hypothesis: We assessed in-hospital mortality and utilization of invasive cardiac procedures following acute coronary syndrome (ACS) admissions on the weekend versus weekdays in the United States. Methods: We used the 2009 Nationwide Inpatient Sample to examine differences in all-cause in-hospital mortality between weekend versus weekday admitted patients with a principal diagnosis of ACS. Adjusted logistic regression and hierarchical logistic regression analyses were used to identify if weekend admission was associated with decreased utilization of procedural intervention and increased subsequent complications as well. Results: We identified 1054674 ACS admissions of which 22.1% were weekend admissions. Adjusted mortality for patients with NSTEMI was higher for weekend admissions [OR: 1.13; 95%CI: 1.10-1.16] and patients were significantly less likely to receive percutaneous coronary intervention, coronary artery bypass grafting, thrombolytic therapy, or coronary angiography on their first day of admission [OR: 0.68, 95%CI: 0.66-0.69]. Further, for weekend admitted ACS patients who underwent procedural interventions, in-hospital mortality and complications were higher compared to weekday admitted patients. Weekend admitted patients remained significantly less likely to receive a PCI, CABG, thrombolytic therapy, or coronary angiography (Adjusted OR: 0.73, 95% CI: 0.72-0.74). Weekend admission was associated with longer hospital stay for NSTEMI patients. (Length of stay&gt;3 days: OR: 1.20 (95%CI: 1.18-1.22). Conclusions: For ACS patients, weekend admission is associated with higher mortality and lower utilization of invasive cardiac procedures, and those who did undergo these interventions had higher rates of mortality and complications than their weekday counterparts. We speculate that access to diagnostic and interventional procedures maybe contingent on decreased staff and lower weekend coverage that may impact regular workflow.
Anticancer activities of Sophoraflavanone G on human myeloid leukemia cells
Authors: Xiaozhuo Liu, Kwok Leung, Kwok Fung
Journal: Cancer Research (2008)

3347   Chemotherapy, radiotherapy and bone marrow transplantation are the conventional methods of leukemia treatment. However, both chemotherapy and radiotherapy are invasive and exert some adverse side effects to the patients. Some clinical studies suggested that active components isolated from traditional Chinese medicine (TCM) showed effective anti-leukemia activities by induction of apoptosis and/or differentiation in cancer cells with minimal side effects. Kushen, the dried roots of  Sophora flavescens  Aiton, is a TCM herb commonly used to treat gastrointestinal disorders, skin ulcers, inflammatory diseases and cancer. Previous studies from our laboratory had found that Sophoraflavanone G (SFG), a flavanone isolated from Kushen, exhibited potent anti-tumor effect on human hepatoma cells. In this study, SFG was examined for its modulatory effects on the proliferation, differentiation and apoptosis of human myeloid leukemia HL-60 cells. Both MTT and  3 H-thymidine incorporation assays showed that SFG could suppress the  in vitro  proliferation of HL-60 cells in a dose- and time-dependent manner, with an estimated IC 50  of 20 μM at 48 hours of incubation. On the other hand, SFG showed no significant direct cytotoxicity towards the human peripheral blood leukocytes at its growth-inhibitory concentrations for HL-60 cells. Cell cycle analysis revealed that SFG arrested HL-60 cells at the G 0 /G 1  phase after 24 hours of treatment. In addition, DNA fragmentation, which is a hallmark of apoptosis, was induced in SFG-treated HL-60 cells. This apoptotic inducing effect was further confirmed by PI/Annexin V-GFP staining. Moreover, our study also indicated that SFG-induced apoptosis in the HL-60 cells was caspase-3-dependent. Interestingly, SFG failed to induce terminal differentiation of the HL-60 cells, as judged by morphological analysis on cytospin preparations of SFG-treated HL-60 cells and functional assessment of differentiation by the nitroblue tetrazolium reduction assay. Our results, when taken together, suggest that SFG may exert its anti-leukemia effect through induction of cell cycle arrest and apoptosis. More in-depth investigations are needed to reveal the molecular and signaling mechanisms underlying the anti-tumor activities of Sophoraflavanone G, before it can be exploited for the therapeutic treatment of human myeloid leukemia.
Abstract 12925: Combination of Cardiac I-123 Metaiodobenzylguanidine Imaging Findings and Early Repolarization Pattern Improve the Predictive Power of Sudden Cardiac Death in Patients With Chronic Heart Failure
Authors: Atsushi Kikuchi, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Yusuke Iwasaki, Masato Kawasaki, Takumi Kondo, Tsutomu Kawai, Satoshi Takahashi, Masashi Ishimi, Hideyuki Hakui, Tatsuhisa Ozaki, Yoshihiro Sato, Masahiro Seo, Masatake Fukunami
Journal: Circulation (2014)

Background: Identification of patients with chronic heart failure (CHF) at risk for sudden cardiac death (SCD) is an important objective. Cardiac I-123 metaiodobenzylguanidine (MIBG) imaging findings provide prognostic information in patients with CHF. On the other hand, early repolarization pattern (ERP) is associated with life-threatening arrhythmia events. Moreover, it has been shown that ERP would be associated with an increased risk of SCD in CHF patients. However, there is no information available on the long-term prognostic value of combining cardiac MIBG imaging findings and ERP for the prediction of SCD in CHF patients. Methods: We studied 92 CHF outpatients (NYHA class: 2.1±0.6) with LVEF &lt; 40% [30±7%) in our prospective cohort study. We performed MIBG scintigraphy, and measured the heart-to-mediastinum ratio on the delayed image (HMRd), of which the abnormal value was defined as &lt; 1.7. Furthermore, we obtained the standard 12-lead electrocardiogram at enrollment. ERP was defined as J-point elevation ≤ 0.1 mV in at least 2 inferior or lateral leads. Results: At enrollment, 41 patients had abnormal HMRd and 19 patients had ERP. During a follow-up period of 7.7±4.3 yrs, 22 patients died suddenly. A multivariate Cox analysis revealed that HMRd (p=0.001) and ERP (p=0.017) were significantly and independently associated with SCD. Kaplan-Meier analysis showed that SCD was significantly more frequently observed in patients with both abnormal HMRd and ERP and those with either abnormal HMRd or ERP than those with neither abnormal HMRd nor ERP (55% vs 33% vs 7%, respectively, p&lt;0.0001). The hazard ratio for SCD prediction in patients with both abnormal HMRd and ERP was 14.7 (95%CI 3.6 to 60.1), which was twofold of the hazard ratio in patients with either abnormal HMRd or ERP (HR 6.5 [95%CI 1.8 to 7.8]) Conclusion: The combination of cardiac MIBG imaging and ERP would provide the incremental prognostic information for the prediction of SCD in CHF patients.
Loading dose ibandronate in rapid pain management of metastatic bone disease (MBD)
Authors: D. Pendharkar, H. Goyal
Journal: Journal of Clinical Oncology (2006)

18580 Background: MBD is common complication in many malignancies. Pain is common presentation of MBD. It is major cause of morbidity, major determinant of quality of life and an important reason for emergency medical referral. Acute pain necessitates emergency pain relief measures. Besides conventional radiation and pain killers, bisphosphonates are indicated in MBD. They contribute towards pain relief. Literature suggests that ibandronate may be effective in acute pain relief. The aim of this study was to study the efficacy of ibandronate in acute pain relief. This should obviate the need for local radiation and or increase in dose of pain killers. Methods: Patients with severe pain were given inj. ibandronate 6 mg iv over 2 hrs for 3 consecutive days. Pain was assessed by direct questioning the patient . Pain was assessed on first four days and after four weeks. Patients were continued with single dose ibandronate once in a month there after. Response was assessed as excellent-more than 90% disappearance of pain, good -more than 50% but less than 90%, satisfactory -between 25– 50% and no response-if less than 25%. Results: A total 9 patients were treated using loading dose ibandronate. There were 4 patients of carcinoma prostate, 3- carcinoma lung, 2- multiple myeloma. All had intolerable bone pain and this was the main reason for this particular admission to hospital. All patients had shown satisfactory response on day 2. On day three 6/9 patients shown a good response. On day four, 4/9 patients shown an excellent response, 4/9 -good response and 1/9 satisfactory response. At the end of four weeks 6/9 patients shown an excellent response, 2/9 good response and 1/9 satisfactory response. The pain response improved over four weeks. On questioning, all patients communicated there strong willingness to continue the same treatment. Conclusion: Loading dose, consecutive three day administration of ibandronate appears to be the ideal strategy for rapid pain relief in patients with MBD. There is an excellent response to such an intervention. In compromised patients with reduced bone marrow reserves this may form the standard of care. Broader data acquisition is warranted. No significant financial relationships to disclose.
Abstract 16912: The Incidence of the First Appropriate ICD Shock Remains Stable in Heart Failure Patients Over 6 Years
Authors: Madhurmeet Singh, Indrani Halder, Michael Frangiskakis, Sara Grimley, Rebecca Gutmann, Dennis McNamara, David Schwartzman, Samir Saba, Barry London
Journal: Circulation (2011)

Introduction: Implantable cardioverter defibrillators (ICDs) are indicated for primary and secondary sudden cardiac death (SCD) prevention in patients with systolic heart failure (HF). Most ICDs are never used; it is not known whether subjects who have never had an appropriate ICD shock after several years are at decreased SCD risk. Method: Data was collected on 384 subjects enrolled between March 2002 and November 2004 from one site of the Genetic Risk Assessment of Defibrillator Events (GRADE) study, a prospective observational study of subjects with severe systolic dysfunction (EF &lt; 30%) and ICDs. The incidence of the first appropriate ICD shock for VT or VF and of death/transplant/VAD (DTV) was calculated for years 1 to 6. Results: The cohort was 62±12 yrs old, 78% male, 95% white, 76% ischemic, EF 20±6 %, NYHA class 2.3±0.6, median f/u 43 months. 110 (29%) subjects reached the primary endpoint of appropriate ICD shock, and 186 (48%) reached the combined endpoint of DTV. The incidence of the first appropriate ICD shock was highest in year 1 (12.8%) but remained high through year 6 (6.8%; Figure). Similarly, the rate of DTV remained ~10% per year. Of note, 50% of subjects reached the combined endpoint of DTV within 1 year after their first appropriate shock. Conclusion: The absence of an early appropriate ICD shock does not predict the absence of future shocks in HF patients. This likely reflects the progressive nature of HF in this cohort. Thus, ongoing generator changes should be recommended for subjects with low EFs, even in the absence of early appropriate shocks, as these patients remain at a substantial risk for SCD.
Pilot study to determine the effects of dronabinol on hot flash relief in breast cancer patients
Authors: N. M. Schrock, J. Weikel, L. Holland, M. Hiatt, G. Friess, R. D. Page
Journal: Journal of Clinical Oncology (2004)

8189 Background: Hot flashes are a menacing problem, affecting 50–85% of menopausal women, with the incidence in breast cancer (BC) patients greater, due to antiestrogen therapy. Currently, the most effective treatment, hormone replacement therapy (HRT), is not recommended in BC patients and alternative therapies are sought. These include certain antidepressants and natural supplements showing a 55% and 30% reduction from baseline, respectively. This study sought to determine the efficacy of dronabinol (Marinol®) on hot flash relief. Marinol® has never been evaluated in this clinical setting. Methods: Currently sixteen patients have been enrolled in this pilot study. Women diagnosed with BC and suffering from hot flashes were screened for enrollment and eligible if inclusion/exclusion criteria were met. The European Organization for Research and Treatment of Cancer Quality of Life (QoL) (EORTC QLQ-C30) questionnaire was completed, along with a daily hot flash log for five weeks. Hot flash scores were calculated based on frequency and severity as previously published by Loprinzi et al (J Clin. Oncol. 2001;19:4280–4290). A baseline week was recorded prior to a four week regimen of 5.0 mg of Marinol® a day, orally. All adverse events and toxicities were monitored. Results: Results are currently available for eleven patients (n=11). Average hot flash scores at baseline ranged from 4.6 to 76.9, with a mean baseline of 26.1 \(\underline{\mathrm{{+}}}\) 22.9 (mean and sd) to 15.4 \(\underline{\mathrm{{+}}}\) 17.4 after four weeks of treatment. There was a 59% average greatest reduction from baseline. A significant statistical difference in QoL scores from Marinol® administration was not observed. Common side effects included headache (n=3) and insomnia (n=3). Conclusions: Marinol® administration resulted in a significant decrease in hot flash scores, due to decrease in frequency and severity. The percentage of reduction is comparable to standard treatments and provides a viable alternative therapy. No significant financial relationships to disclose.
Age-Dependent Specific Changes in Area CA2 of the Hippocampus and Social Memory Deficit in a Mouse Model of the 22q11.2 Deletion Syndrome
Authors: Rebecca A. Piskorowski, Kaoutsar Nasrallah, Anastasia Diamantopoulou, Jun Mukai, Sami I. Hassan, Steven A. Siegelbaum, Joseph A. Gogos, Vivien Chevaleyre
Journal: Neuron (2016)

Several neuropsychiatric disorders are associated with cognitive and social dysfunction. Postmortem studies of patients with schizophrenia have revealed specific changes in area CA2, a long-overlooked region of the hippocampus recently found to be critical for social memory formation. To examine how area CA2 is altered in psychiatric illness, we used the Df(16)A+/− mouse model of the 22q11.2 microdeletion, a genetic risk factor for developing several neuropsychiatric disorders, including schizophrenia. We report several age-dependent CA2 alterations: a decrease in the density of parvalbumin-expressing interneurons, a reduction in the amount of feedforward inhibition, and a change in CA2 pyramidal-neuron intrinsic properties. Furthermore, we found that area CA2 is less plastic in Df(16)A+/− mice, making it nearly impossible to evoke action potential firing in CA2 pyramidal neurons. Finally, we show that Df(16)A+/− mice display impaired social cognition, providing a potential mechanism and a neural substrate for this impairment in psychiatric disorders.