tbuckley/cabot-search huggingface dataset:
Mannose-binding lectin (MBL) serum level and genotype and risk of chemotherapy-induced febrile neutropenia (FN) in patients with solid tumors.
Authors: J. Goudzwaard, W. Edward Fiets, G.J. van de Geijn, T. Njo, J.M Zuetenhorst, E. Birnie, R. H.N. van Schaik, M. van der Putten, Marco Polee, Paul Hamberg
Journal: Journal of Clinical Oncology (2014)

e20653 Background: MBL is part of the innate immune system and deficiency in serum-MBL is in theory associated with an increase in infections during chemotherapy, although the exact cut-off levels for deficiency are debated. The risk of chemotherapy induced FN depends on several factors including host as well as therapy related factors. Identifying those patients at higher risk of FN creates the opportunity for preventive measures. This cohort study aimed to evaluate the impact of MBL-serum levels as well as MBL-genotype on the risk of FN. Methods: Patients treated with (neo-)adjuvant or palliative chemotherapy for a solid malignancy with a priori an intermediate FN-risk were eligible. No primary antibiotic or growth factor prophylaxis was allowed. MBL was measured at baseline and prior to cycle 2. In patients with FN additional MBL samples were drawn. The cut-off level for MBL deficiency was <0.8 mcg/ml. MBL genotyping was performed using PCR on genomic DNA isolated from blood. Results: 182 patients were enrolled and evaluable. The most commonly used chemotherapy schedules were: FEC/Docetaxel (n=92); carboplatin/paclitaxel (n=37) and adriamycine/cyclophosphamide (n=25). 42% of patients were MBL-deficient at baseline.A total of 39 episodes of FN were observed. The number of FN in the MBL-deficient group was 14/77 (18.2%) vs. 25/105 (23.8%) in the MBL-non-deficient group. (RR 0.765, p=0.36). Median baseline MBL in patients with FN was 1.39 mcg/ml and in non-FN patients 1.10 mcg/ml (p =0.92) The change in MBL between baseline and cycle 2 was not associated with the risk of FN (median change of MBL:+0.19 (FN group) vs. +0.06 (FN-free group), p=0.39). In 27 of the FN-episodes a MBL sample was collected < 24 hours of FN-diagnosis At that time 33.3% was MBL-deficient with a higher median MBL compared to baseline (+0.37 mcg/ml; p<0.001). Two promotor (-550 H/L and -221 X/Y) and three exon polymorphisms (52 A/D; 54 A/B and 57 A/C) were evaluated and none of them was predictive for developing FN. Conclusions: Neither MBL-deficiency nor a specific MBL-genotype is associated with increased risk of FN. However, MBL significantly increased at the time of febrile neutropenia. Clinical trial information: NTR3398.
Impact of early responses in the outcome of patients with newly diagnosed CML-CP, evaluated by FISH in countries where standard cytogenetics are not available or reliable.
Authors: Christianne Bourlon, Carlos Francisco Hernandez-Mata, Maria Teresa Bourlon, Elena Tuna-Aguilar, Alvaro Aguayo
Journal: Journal of Clinical Oncology (2014)

e18027 Background: Imatinib (IM) achieves complete cytogenetic response (CCyR) in 87% of chronic phase chronic myeloid leukemia (CML-CP). Monitoring response is fundamental, not achieving CCyR at 12m is associated to higher rates of progression. Karyotype (KT) is standard for monitoring, FISH is an alternative method, few studies have correlated both. In Latin America monitoring is done in 31% at 3m and 54% at 6m, 72% by KT and 19% FISH. No study has validated FISH and its prognostic value in countries were KT has a high rate of failure and there is no standardized PCR. Methods: Patients >18y with CML-CP on IM 400mg as frontline therapy with 18m of follow-up from 2003 to 2012 at our institution were included. Clinical data, citogenetics at diagnosis and monitoring were collected retrospectively. Pearson correlation between KT and FISH, survival and time-to-event curves by Kaplan-Meir method and log rank test were performed. Results: We found 73 (84%) patients with CML-CP, 65 fulfilled inclusion criteria. Median age 38y, 56% male, 83% were symptomatic. EUTOS risk score was low in 66% and high in 27%. KT and/or FISH available in 100, 47, 84, 84 and 76% at diagnosis, 3, 6, 12 and 18m. KT was done in 223 samples reported successful in 37% and FISH in 236 samples reported successful 92%. Pearson correlation between KT and FISH was 0.98 (CI95% 0.97-0.99) in samples with successful reports for both tests (n=121). Median follow-up was 61m. CCyR was obtained in 27% at 3m, 43% at 6m, 61% at 12m and 66% at 18 m. OS, EFS and TFS were 87, 78 and 64% at 5 years. Difference among response groups evaluated by FISH at 3, 6, 12 and 18m did not reach significant difference in OS or TFS. Patients who achieved CCyR had significantly better EFS at 3m 100 vs 94 vs 33% (<0.001) and at 6 months 100 vs 50 vs 33% (<0.001) for CCyR, PCyR and MinCyR. Conclusions: In our series rate of failure of KT is 62% in contrast with 7% for FISH. In successful samples a high correlation among tests was found. FISH response at 3 and 6m in our cohort was associated with better EFS. Given this data we suggest using FISH at 3 and 6m as an acceptable monitoring test, and patients lacking a CCyR at these times might be candidates for therapy modifications.
Emerging Clinical Activity of REGN1979, an Anti-CD20 x Anti-CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Follicular Lymphoma (FL), Diffuse Large B-Cell Lymphoma (DLBCL), and Other B-Cell Non-Hodgkin Lymphoma (B-NHL) Subtypes
Authors: Rajat Bannerji, Jon E. Arnason, Ranjana Advani, Jennifer R. Brown, John N. Allan, Stephen M. Ansell, Jeffrey Barnes, Susan M. O'Brien, Julio C. Chavez, Johannes Duell, Israel Lowy, Robert Charnas, David Sternberg, Srikanth Ambati, Lieve Adriaens, Melanie Ufkin, Xiaoyu Yan, Jingjin Li, Mark Navarro, Peter Gasparini, Vladimir Jankovic, Nathalie Fiaschi, Wen Zhang, Sara Hamon, Gavin Thurston, Max S. Topp
Journal: Blood (2018)
Piezo1-Sensitive Biomechanical Pulsation Stimulates Long-Term Hematopoietic Stem Cell Formation
Authors: Giorgia Scapin, Jennifer Cillis, Taylor Patch, Priyanka R Dharampuriya, Elliott J. Hagedorn, Vanessa Lundin, Owen J Tamplin, Heidi Andeson, Leonard I. Zon, George Q. Daley, Dhvanit I Shah
Journal: Blood (2018)
Clinical impact of the interaction of gastric acid suppressive agents and gefitinib.
Authors: Yasushi Murakami, Hideo Saka, Masahide Oki, Chiyoe Kitagawa, Yoshihito Kogure
Journal: Journal of Clinical Oncology (2014)

e19146 Background: Gefitinib requires an acidic environment for maximal absorption and it is recommended that gastric acid suppressive agents (GAS) such as the proton-pump inhibitor or the histamine 2 receptor antagonist should not be taken concurrent with gefitinib. The aim of this study was to evaluate the clinical impact of concomitant GAS use on patients with non-small cell lung cancer (NSCLC) who were treated with gefitinib. Methods: We retrospectively analyzed the medical record of patients with NSCLC who received gefitinib as initial treatment from November 2008 to December 2011 at Nagoya Medical Center. We compared GAS users and GAS non-users with respect to overall survival (OS) and progression-free survival (PFS) by use of the Kaplan–Meier method and log-rank test. In addition, the differences of objective response rates (ORR), adverse events were analyzed by Fisher’s exact test. Results: Thirty-seven patients (14 males and 23 females, median 77 years) were included in this study. The histologic subtype of all patients was adenocarcinoma harboring sensitizing EGFR mutations. GAS was concurrently taken with gefitinib in 18 patients (49%) and not in 19 patients (51%). In all 37 patients, ORR was 57%, and the median OS and PFS was 21.0 months and 8.2 months respectively. There were not statistically significant difference in PFS (median, 11.4 months vs. 6.1 months, p=0.21), OS (median, 20.8 months vs. 23.7 months, p=0.57) and ORR (61% vs. 53%, p=0.51) between GAS users and GAS non-users. Rash, diarrhea and liver dysfunction of not less than grade 2 was similar frequency between both groups. Conclusions: This retrospective study showed that co-administration of GAS did not appear to have a significant impact on patients with NSCLC who were treated with gefitinib.
Extracellular vesicle-mediated reversal of taxane resistance and the malignant phenotype in prostate cancer.
Authors: Omar Nadeem, Anthony E. Mega, Evan T. Keller, Joseph F. Renzulli, Peter J. Quesenberry, Devasis Chatterjee
Journal: Journal of Clinical Oncology (2014)

e16028 Background: Castrate resistant prostate cancer (CRPC) is the second leading cause of cancer-related death in men in the developed world. Several new therapies, including taxane-based chemotherapy, have improved outcomes for CRPC. However, new therapeutic regimens and rational targets are needed in order to continue to improve prostate cancer (PCa) patient survival. We studied the role of extracellular vesicles (EVs) in reversing taxane resistance and the malignant phenotype in PCa. Methods: In addition to soluble paracrine factors, many tumor cells also release EVs, which can alter the tumor microenvironment and promote disease progression. We isolated EVs from normal, non-malignant prostate cells and from biopsied tissue from patients with high grade (Gleason score 8-10) PCa. EVs were co-cultured for 7 days with recipient non- or malignant prostate cells after which: sensitivity to paclitaxel was monitored via MTT assay; the induction or transfer of proteins was determined via mass spectrometry and Western blot analysis; and anchorage independent and tumor xenograft growth were assessed. Results: High grade EVs significantly induced anchorage independent growth and the malignant phenotype of non-malignant prostate cells. We identified proteins via antibody analysis and mass spectrometry that may be responsible for EV-mediated phenotypic changes. We identified increased protein levels of putative mediators of the EV-induced changes including 14-3-3 zeta, pRKIP and prohibitin. (log p value <0.05 for all 3 proteins as determined by the Comparison Analysis Tool in the IPA software) in non-malignant cells co-cultured with PCa patient EVs. Knockdown of 14-3-3 zeta lead to partial reversal of soft agar growth, indicating that it is a potential candidate for targeted therapy. Co-culture of malignant PCa cells with non-malignant prostate EVs significantly inhibited tumor xenograft growth and reversed resistance to paclitaxel, which was concomitant with the transfer/induction of the androgen receptor. Conclusions: Our study provides a rational basis for the use of non-cancer cell-derived EVs to potentially reverse taxane resistance and inhibit CRPC progression.
A Randomized Trial of Zoledronic Acid to Prevent Bone Loss in the First Year after Kidney Transplantation
Authors: Igor Denizarde Bacelar Marques, Maria Júlia Correia Lima Nepomuceno Araújo, Fabiana Giorgetti Graciolli, Luciene Machado dos Reis, Rosa Maria R. Pereira, Jackeline C. Alvarenga, Melani Ribeiro Custódio, Vanda Jorgetti, Rosilene Motta Elias, Rosa Maria Affonso Moysés, Elias David-Neto
Journal: Journal of the American Society of Nephrology (2019)

Bone and mineral disorders commonly affect kidney transplant (KTx) recipients and have been associated with a high risk of fracture. Bisphosphonates may prevent or treat bone loss in such patients, but there is concern that these drugs might induce adynamic bone disease (ABD).In an open label, randomized trial to assess the safety and efficacy of zoledronate for preventing bone loss in the first year after kidney transplant, we randomized 34 patients before transplant to receive zoledronate or no treatment. We used dual-energy x-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and bone biopsies to evaluate changes in bone in the 32 evaluable participants between the time of KTx and 12 months post-transplant.Both groups of patients experienced decreased bone turnover after KTx, but zoledronate itself did not affect this outcome. Unlike previous studies, DXA showed no post-transplant bone loss in either group; we instead observed an increase of bone mineral density in both lumbar spine and total hip sites, with a significant positive effect of zoledronate. However, bone biopsies showed post-transplant impairment of trabecular connectivity (and no benefit from zoledronate); HR-pQCT detected trabecular bone loss at the peripheral skeleton, which zoledronate partially attenuated.Current immunosuppressive regimens do not contribute to post-transplant central skeleton trabecular bone loss, and zoledronate does not induce ABD. Because fractures in transplant recipients are most commonly peripheral fractures, clinicians should consider bisphosphonate use in patients at high fracture risk who have evidence of significantly low bone mass at these sites at the time of KTx.
Treatment of lung cancer in Greenland 2004-2010.
Authors: Signe Risum, Allan Gelvan, Mikael Andersson, Seppo W. Langer
Journal: Journal of Clinical Oncology (2014)

e17609 Background: In Greenland, the incidence of lung cancer (LC) is now as high as in the other Nordic countries; 59.8/100,000 for men and 43.9/100.000 for women. In 2004, oncological treatment of LC following Danish guidelines became available to LC patients in Greenland. We performed a retrospective evaluation of treatment results and overall survival (OS) after the first six years of LC treatment in Greenland. Methods: From September 2004 to August 2010, 173 patients with LC were referred to treatment at Queen Ingrid’s Hospital in Nuuk. OS was calculated as the interval from the date of diagnosis to the date of death or to February 1, 2014; follow-up was > 30 months. Survival analysis was done with the method of Kaplan and Meier and the log-rank test. P < 0.05 was the level of significance. Results: The mean age at diagnosis was 63 years (range 26 – 87 years). Histological diagnoses and stages are shown in Table 1. Of the 173 patients, 142 (82%) received treatment; 20 patients underwent surgery (10 stage Ib, 1 stage IIa, 5 stage IIb, 4 stage IIIa); 11 patients had a lobectomy and 9 patients had a pneumonectomy (9 patients had postoperative chemotherapy). Palliative chemotherapy (PC) was given to 122 of the 142 treated patients (86%); 36 patients (30%) had second line chemotherapy. The median survival of patients undergoing primary surgery, PC, and no treatment was 76.3 months, 11.8 months, and 2.0 months, respectively (P<0.0001). Conclusions: Evaluation of the first six years of LC treatment in Greenland showed that treatment according to Danish guidelines is feasible and long-term survivors were seen. To further decrease mortality from LC, health care resources should continue to be allocated to the prevention and treatment of LC in Greenland. Histologic diagnoses and stages in 173 patients with lung cancer. Diagnosis/stages Number of patients Small cell lung cancer (SCLC) 28 (16%) Limited disease 4 Extensive disease 24 Non-small cell lung cancer (NSCLC) 145 (84%) Squamous cell carcinoma 81 (56%) Stage Ib 10 Stage IIa 1 Stage IIb 7 Stage IIIa 13 Stage IIIb 27 Stage IV 23 Adenocarcinoma 49 (34%) Stage Ib 2 Stage IIb 1 Stage IIIa 8 Stage IIIb 19 Stage IV 19 Large cell carcinoma 3 (2%) (1 stage IIIa, 1 stage IIIb,1 stage IV) Not otherwise specified 12(8%) (2 stage IIIa, 3 stage IIIb, 7 stage IV)
FRI0261 Assessment of autophage function in systemic lupus erythematosus in respect of hyperlipidemia and immunosuppressive drugs
Authors: A.S. Hamada, M.I. aref, W.A. salahdin
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Autophagy is an orchestrated homeostatic process to eliminate unwanted proteins and damaged organelles. Lipid turnover, as well, is controlled by autophagy through a process described as lipophagy. Defective lipophagy has been already linked to important metabolic disorders such as fatty liver, obesity and atherosclerosis. <h3>Objectives</h3> Assessment of autophagy focusing on lipids regulation in untreated newly diagnosed systemic lupus Erythematosus (SLE) patients and after three months of treatment with immunosuppressive drugs. <h3>Methods</h3> Subjects in this study have been divided into three groups. Group 1 included 60 newly diagnosed SLE patients before receiving any treatment, group2 included the same subjects of group 1 after three months of treatment with immunosuppressive drugs and group 3 included 30 healthy donors of matched age and sex as a control group. For each subject, disease activity was assessed by (SLEDAI) score, lipid profile was measured in addition to evaluation of lipids uptake, enhanced phagocytosis and intracellular killing ability of monocytes and neutrophils using Sudan Black B stain and Nitroblue tetrazolium stain mixed with latex particles coated with antibodies. Microscopic pictures were captured and quantified by ImageJ. <h3>Results</h3> 95% of patients were females(57/60) with mean of age(39.7±8.6). Mean of SLEDAI score in group 1 was (18.6±3.4) decreased in group 2 (3 months after treatment) to (10.4±4.2). There was a positive correlation between total cholesterol, LDL and triglycerides and disease activity(SLEDAI score) (r=0.677, r=0.603 and r=0.718; respectively). On the contrary, There was a negative correlation between HDL and disease activity(r=−0.396). Furthermore, there was a negative correlation between lipid content of cells and intracellular killing and disease activity(r=−0.258 and r= −0.324; respectively). After 3 months, 100% of patients were taking Corticosteroids and Hydroxychloroquine(60/60).18.3% of patients received Azathioprine(11/60), 40.0% received Cyclophosphamide(24/60) and 15% received Mycophenolate(9/60) besides Corticosteroids and Hydroxychloroquine. Comparing group 2 to group 1, there was significant increase in cholesterol, LDL and trigycerides (p=0.027, p=0.021 and p=0.017; respectively) while HDL showed insignificant difference(p=0.0740). Lipid content in cells and intracellular killing significantly decreased(p=0.0322 and p=0.0271; respectively). <h3>Conclusions</h3> Autophagy is deficient in patients with SLE aggravated by immunosuppressive drugs so they are more susceptible to infections and dyslipidemia. Consequently, lipid lowering drugs are definitely required to decrease comorbidity. <h3>Disclosure of Interest</h3> None declared
Death less than one month from diagnosis in children with cancer: A population-based analysis.
Authors: Adam L. Green, Elissa Furutani, Karina Braga Ribeiro, Carlos Rodriguez-Galindo
Journal: Journal of Clinical Oncology (2014)

1531 Background: Childhood cancer outcomes continue to improve, but a proportion of patients still die soon after diagnosis. While many of these deaths may be preventable, this group of patients has not been well characterized and may be underreported. Methods: We retrieved data from SEER 13 on the 34,878 patients 0-19 yrs with cancer diagnosed between 1992 and 2010. Early death (ED) was defined as death within the first month from diagnosis. Demographic, clinical, and socioeconomic factors were analyzed using chi-square testing. Socioeconomic data for each county were derived from Census 2000 and divided into two categories according to the median value for the cohort. Results: 1.8% (n=644) patients died within one month of diagnosis. Compared with the entire cohort, the ED group had a significantly higher percentage of infants (25.3% vs.7.2%, p<0.0001). In comparison to the whole cohort, diseases overrepresented in the ED group included infant ALL (2.0 vs 0.6%, p<0.0001), AML (18.2 vs 5.0%, p<0.0001), CNS tumors (24.8 vs 17.7%, p<0.0001), and hepatic tumors (3.7 vs 1.4%, p<0.0001). Diseases underrepresented included ALL, lymphomas, and renal, bone, and soft tissue tumors. Patients in the ED group were more likely to be of non-white race (24.5% vs. 20.4%, p=0.03) or Hispanic ethnicity (33.8% vs. 26.1%, p<0.0001). These patients were also more likely to live in counties with high rates of poverty (p<0.0001), unemployment (p=0.03), language isolation (p=0.0004), and immigration (p=0.003), and a low rate of high school education (p=0.02). Early death rate decreased over the period of analysis (APC -2.6%). Conclusions: Risk factors for ED in childhood cancer include infancy, specific diagnoses such as AML and CNS tumors, racial and ethnic minority, and disadvantaged socioeconomic status. The disease-specific rates of early death found in this population analysis were uniformly higher than those reported in large cooperative clinical trials, suggesting that many ED patients are lost to the medical literature. This group should be described prospectively, and initiatives to identify patients at risk and develop preventive interventions should be undertaken in the primary and specialty settings.
Dietary, physical activity, and weight management interventions among active-duty military personnel: a systematic review
Authors: Ahmad M. Malkawi, Ree M. Meertens, Stef P. J. Kremers, Ester F. C. Sleddens
Journal: Military Medical Research (2018)

Research has been conducted to assess the effectiveness of weight management, dietary and physical activity interventions in military settings. However, a recent and comprehensive overview is lacking. The aim of this systematic review is to examine the evidence and describe key components of effective interventions in terms of improving body composition, dietary behaviors, and physical activity among active-duty military personnel. PubMed, PsycInfo, and CINAHL were searched on the 17th of November 2017 to identify interventions that promoted diet and/or physical activity among active-duty military personnel. Studies were included if they assessed outcomes related to anthropometric measurements, dietary behaviors, or fitness/physical activity levels. There were no restrictions regarding publication date, follow-up duration, and sex. After screening, a total of 136 studies were eligible. Of these studies, 38 included an educational and/or behavioral change component, and 98 had only physical or fitness training as part of basic military training. Only studies that included an educational and/or behavioral change component were assessed for quality using the Effective Public Health Practice Project tool and included in the qualitative synthesis of the results. Based on consistent evidence from studies that were rated as moderate or strong, there is good evidence that military weight management interventions are effective in improving body composition for durations of up to 12 months. Effective interventions are more likely to be high intensity (have a greater number of sessions), are more often delivered by specialists, and use theoretical base/behavioral change techniques and a standardized guideline. Dietary interventions can potentially reduce total fat and saturated fat intake. Dietary interventions that target the kitchen staff and/or increase the availability of healthy food are more likely to be effective in the short term. The results regarding military physical fitness interventions were inconclusive. Despite limitations such as the diversity and heterogeneity of the included interventions, outcome measurements, and follow-up duration, this systematic review found good evidence that weight management interventions are effective, especially in terms of weight loss. More studies are needed to acquire solid evidence for effectiveness for durations longer than 12 months and to identify key components of the effective dietary and physical activity educational and/or behavioral change interventions, especially in countries outside Europe and the US.