tbuckley/cabot-search huggingface dataset:
An overview of clinical and economic outcomes of U.S. veteran colorectal cancer patients.
Authors: Onur Baser, Elyse Fritschel, Lu Li, J Zhang, Li Wang
Journal: Journal of Clinical Oncology (2013)

e14689 Background: Colorectal cancer is the second leading cause of cancer-related death in the United States. While studies have shown that conditions such as diabetes are associated with shorter disease-free survival in colon cancer patients, fewer U.S. Department of Veterans Affairs (VA)-specific studies have been conducted focusing on colorectal cancer outcomes (Centers for Disease Control and Prevention. Colorectal (colon) cancer. www.cdc.gov/cancer/colorectal. Extermann M. Interaction between comorbidity and cancer. Cancer Control. 2007; 14(1): 13-22). This study aimed to describe the comorbidity profile and economic outcomes of colorectal cancer patients in the VA population. Methods: A retrospective study of patients diagnosed with colorectal cancer during the study period of October 1, 2005 to September 30, 2010 was conducted using the Veterans Health Administration datasets. All colorectal cancer patients were identified using International Classification of Disease 9 th Revision Clinical Modification (ICD-9-CM) diagnosis codes 153.xx and 154.xx. Descriptive statistics were calculated as means ± standard deviation (SD) and percentages using SAS version 9.3 software. Results: In diagnosed colorectal cancer patients (n=62,200), common comorbidities included hypertension (n=18,309, 29.44%) and diabetes (n=10,891, 17.51%). Other minor comorbidities included hyperlipidemia and benign neoplasm of the colon. The average Fecal Occult Blood Test result (found in 12.21% of colorectal cancer veterans) was 96.37. Outpatient services were utilized by 99.71% of colorectal cancer patients, followed by pharmacy (91.94%) and inpatient visits (31.15%). Costs for outpatient ($10,637, SD=$17,125), pharmacy ($2,704, SD=$9,773), and inpatient services ($16,032, SD=$53,078) contributed to follow-up health care expenditures. Conclusions: Despite frequent outpatient utilization, inpatient costs have the greatest impact on the considerable health care cost incurred by lung cancer veterans. The presence of comorbid conditions may further complicate colorectal cancer treatment, though further characterization requires further research.
Circulating tumor DNA as a potential marker of adjuvant chemotherapy benefit following surgery for localized pancreatic cancer
Authors: B. Lee, L. Lipton, J. Cohen, J. Tie, A.A. Javed, L. Li, D. Goldstein, M. Burge, P. Cooray, A. Nagrial, N.C. Tebbutt, B. Thomson, M. Nikfarjam, M. Harris, A. Haydon, B. Lawrence, D.W.M. Tai, K. Simons, A.M. Lennon, C.L. Wolfgang, C. Tomasetti, N. Papadopoulos, K.W. Kinzler, B. Vogelstein, P. Gibbs
Journal: Annals of Oncology (2019)
Triamcinolone acetonide-loaded PLA/PEG-PDL microparticles for effective intra-articular delivery: synthesis, optimization, in vitro and in vivo evaluation
Authors: May Abou-ElNour, Rania A.H. Ishak, Mattia Tiboni, Giulia Bonacucina, Marco Cespi, Luca Casettari, Mahmoud E. Soliman, Ahmed S. Geneidi
Journal: Journal of Controlled Release (2019)
Oral antibiotic use and risk of colorectal cancer in the United Kingdom, 1989–2012: a matched case–control study
Authors: Jiajia Zhang, Charles Haines, Alastair J M Watson, Andrew R Hart, Mary Jane Platt, Drew M Pardoll, Sara E Cosgrove, Kelly A Gebo, Cynthia L Sears
Journal: Gut (2019)

Background Microbiome dysbiosis predisposes to colorectal cancer (CRC), but a population-based study of oral antibiotic exposure and risk patterns is lacking. Objective To assess the association between oral antibiotic use and CRC risk. Design A matched case–control study (incident CRC cases and up to five matched controls) was performed using the Clinical Practice Research Datalink from 1989 to 2012. Results 28 980 CRC cases and 137 077 controls were identified. Oral antibiotic use was associated with CRC risk, but effects differed by anatomical location. Antibiotic use increased the risk of colon cancer in a dose-dependent fashion (p trend &lt;0.001). The risk was observed after minimal use, and was greatest in the proximal colon and with antibiotics with anti-anaerobic activity. In contrast, an inverse association was detected between antibiotic use and rectal cancers (p trend =0.003), particularly with length of antibiotic exposure &gt;60 days (adjusted OR (aOR), 0.85, 95% CI 0.79 to 0.93) as compared with no antibiotic exposure. Penicillins, particularly ampicillin/amoxicillin increased the risk of colon cancer (aOR=1.09 (1.05 to 1.13)), whereas tetracyclines reduced the risk of rectal cancer (aOR=0.90 (0.84 to 0.97)). Significant interactions were detected between antibiotic use and tumour location (colon vs rectum, p interaction &lt;0.001; proximal colon versus distal colon, p interaction =0.019). The antibiotic–cancer association was found for antibiotic exposure occurring &gt;10 years before diagnosis (aOR=1.17 (1.06 to 1.31)). Conclusion Oral antibiotic use is associated with an increased risk of colon cancer but a reduced risk of rectal cancer. This effect heterogeneity may suggest differences in gut microbiota and carcinogenesis mechanisms along the lower intestinal tract.
Treatment of patients (pts) with chronic myeloid leukemia (CML) and imatinib failure after developing BCR-ABL kinase mutations with allogeneic stem cell transplantation (ASCT)
Authors: R. E. Champlin, E. Jabbour, J. Cortes, H. Kantarjian, B. S. Andersson, S. Giralt, M. De Lima
Journal: Journal of Clinical Oncology (2006)

6545 Background: ASCT is curative for many pts with CML, and may be effective after imatinib failure. Resistance to imatinib is most often associated with point mutations in the Bcr-Abl kinase domain. The outcome of pts with Bcr-Abl kinase mutations after ASCT is not known. Methods: We assessed the outcome of ASCT in 10 pts with CML (chronic phase [CP]=3, accelerated phase [AP]=4, blast phase [BP]=3) harboring 9 different protein kinase mutations. P-loop mutations were detected in 5 (50%) pts; the most common type of mutation was T315I detected in 2 pts (one AP and one CP). At the time of ASCT, one pt was in major molecular remission (MMR) (BP, Q252H), one was in major cytogenetic response (CP, T315I), and 2 were in complete hematologic response (2 BP, Y253H and E255K). Preparative regimen was busulfan based regimen in 7 and fludarabine + melphalan in 3 pts. Eight male and 2 female pts, median age of 44 years (range, 26–63 years), received their ASCT between July 2002 and October 2005. Donor was fully matched related in 5 (50%) and unrelated in 5 (50%) pts. Source of stem cells was peripheral blood and bone marrow in 3 and 7 pts, respectively. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and mini methotrexate. Results: All patients engrafted; there was no treatment-related mortality. Chimerism studies at day 30 and 100 post ASCT were available in 9 pts and were 100% of donor type in all but one. Nine pts responded: 7 achieved a complete molecular remission (CMR) and 2 achieved a MMR. Two (22%) pts (Q252H [BP] and T315I [AP]) relapsed and died of disease progression after a median of 9 months. All the remaining 7 pts were in CMR for a median of 17 months (range, 3–22+ months). Conclusions: ASCT is an important salvage option for pts who develop resistance to imatinib through Bcr-Abl mutations. Early introduction of such strategy may result in better outcome. No significant financial relationships to disclose.
Effects of depression on quality of life in Medicare beneficiaries with prostate cancer
Authors: C. Chang, S. J. Knight, C. L. Bennett
Journal: Journal of Clinical Oncology (2006)

8510 Background: Depression is very common in the elderly and is particularly costly because of associated mortality, excess disability, and interactions with other physical health problems. We aimed to examine the impact of depression on quality of life in the older prostate cancer patients receiving Medicare benefits. Methods: Data came from the 2003 Cohort VI Baseline Medicare Health Outcomes Survey. Among the 109,115 individuals, only those who were under treatment for prostate cancer and completed the survey themselves were included in this study (n=2,191). Quality of life was assessed using the SF-36 questionnaire and the physical and mental health component scores (higher scores indicating better health) were analyzed. Results: Eighty-eight percent were whites, 75% were married, 76% had at least high school education, 45% were aged 65 to 74, and 55% were aged 75 and older. Those who reported having been depressed in the past two weeks (n=453; 21%) had significantly lower physical health (34.06 vs. 40.24; p &lt; .001) and mental health (41.14 vs. 54.41; p &lt; .001) than those who did not. Similar patterns were observed for those who endorsed questions indicating “depression much of the time in the past year” and “depression most of the time in the past 2 years”. Conclusions: Depression is prevalent among older men diagnosed with prostate cancer, and those who acknowledge being depressed in the past 2 weeks to 2 years have significantly worse mental and physical health. Attention to depression, in addition to prostate cancer specific issues, should be considered among prostate cancer patients who report mental or physical health problems. Early detection and treatment of depression in this population could potentially alleviate their suffering and improve their quality of life. No significant financial relationships to disclose.
Abstract 12834: Effects of Different Targeted Temperature on the Outcomes of CPR in a Rat Model of Cardiac Arrest
Authors: Ziren Tang, Zhengfei Yang, Jiangang Wang, Lu Yin, Shen Zhao, Xiaobo Wu, Jena Kline, Wanchun Tang
Journal: Circulation (2015)

Introduction: Therapeutic hypothermia improves the outcomes following resuscitation. The current hypothermia range (32-34°C) recommended by the American Heart Association is based mainly on two clinical studies. The benefits and the adverse effects of the temperature management at this range are still controversial. In the present study, we compared the effects of different body temperatures (33°C, 36°C, 37°C and 38°C) after resuscitation on the outcomes of CPR in a rat model of cardiac arrest. Methods: Ventricular fibrillation was electrically induced and untreated for 8 mins. Defibrillation was attempted after 8 mins of CPR. The animals were then randomized into 4 groups ( n =10): hypothermia at 33°C (T33), hypothermia at 36°C (T36), normothermic (T37) and hyperthermia (T38). The variable core temperatures were maintained for 6 hours. Myocardial function and sublingual microcirculation were measured at baseline, 1, 2, 3 and 6 hours after the return of spontaneous circulation (ROSC). Survival and neurological function were evaluated at 24, 48 and 72 hours after ROSC. Results: The measurements were significantly better in the animals treated with hypothermia regardless of the cooling depth when compared with the normothermic group. Better sublingual microcirculation at 6 hours post-resuscitation was observed in the T36 group when compared with the T33 group. Significantly worse myocardial function and sublingual microcirculation were observed in the T38 animals when compared to the T37 group. Conclusions: Mild reduction of core temperature to 36°C early after ROSC improved post-resuscitation myocardial and neurological functions and survival to the same extent as 33°C but with less impairment of microcirculation.
Altered immune system in frailty: Genetics and diet may influence inflammation
Authors: Orietta Pansarasa, Cristiana Pistono, Annalisa Davin, Matteo Bordoni, Maria Chiara Mimmi, Antonio Guaita, Cristina Cereda
Journal: Ageing Research Reviews (2019)

Frailty is a complex geriatric syndrome associated with biological vulnerability to stressors and decreased physiological reserve. Its etiology and pathogenesis are not completely understood, although various causes and complex pathways have been proposed. Immune system alterations (immunosenescence and "InflammAging") have been suggested to contribute to frailty, but a precise causative role of such alterations remains to be determined. Genetic studies support the suggestion of immune system involvement in frailty: genetic variants in genes involved in immune system function have been associated with the syndrome. Interestingly, nutritional status, through its effects on cellular metabolism, may also influence the immune system, i.e. hormone and cytokine (mainly adipocytokine) levels, and immune cell populations and function, increasing inflammation and contributing to frailty. This review aims to discuss the role of immune system alterations in frailty, analyzing the role of genetic factors in frailty onset and the impact of diet on inflammation and, in turn, on frailty.
Universal atrial coordinates applied to visualisation, registration and construction of patient specific meshes
Authors: Caroline H. Roney, Ali Pashaei, Marianna Meo, Rémi Dubois, Patrick M. Boyle, Natalia A. Trayanova, Hubert Cochet, Steven A. Niederer, Edward J. Vigmond
Journal: Medical Image Analysis (2019)

Integrating spatial information about atrial physiology and anatomy in a single patient from multimodal datasets, as well as generalizing these data across patients, requires a common coordinate system. In the atria, this is challenging due to the complexity and variability of the anatomy. We aimed to develop and validate a Universal Atrial Coordinate (UAC) system for the following applications: combination and assessment of multimodal data; comparison of spatial data across patients; 2D visualization; and construction of patient specific geometries to test mechanistic hypotheses. Left and right atrial LGE-MRI data were segmented and meshed. Two coordinates were calculated for each atrium by solving Laplace's equation, with boundary conditions assigned using five landmark points. The coordinate system was used to map spatial information between atrial meshes, including scalar fields measured using different mapping modalities, and atrial anatomic structures and fibre directions from a reference geometry. Average error in point transfer from a source mesh to a destination mesh and back again was less than 0.1 mm for the left atrium and 0.02 mm for the right atrium. Patient specific meshes were constructed using the coordinate system and phase singularity density maps from arrhythmia simulations were visualised in 2D. In conclusion, we have developed a universal atrial coordinate system allowing automatic registration of imaging and electroanatomic mapping data, 2D visualisation, and patient specific model creation.
Carfilzomib with immunomodulatory drugs for the treatment of newly diagnosed multiple myeloma
Authors: Ola Landgren, Pieter Sonneveld, Andrzej Jakubowiak, Mohamad Mohty, Karim S. Iskander, Khalid Mezzi, David S. Siegel
Journal: Leukemia (2019)

Carfilzomib, a selective proteasome inhibitor (PI), is approved for the treatment of patients with relapsed or refractory multiple myeloma (MM). Combination regimens incorporating a PI and immunomodulatory drug (IMiD) have been associated with deep responses and extended survival in patients with newly diagnosed MM (NDMM). Carfilzomib-based combinations with immunomodulators are being extensively studied in the frontline setting. The objective of this review was to describe efficacy and safety data for carfilzomib-based, PI/immunomodulatory combinations in NDMM. Information sources were articles indexed in PubMed and abstracts from key hematology/oncology congresses published between January 2012 and December 2018. PubMed and congresses were searched for prospective clinical studies assessing the combination of carfilzomib with an IMiD for NDMM treatment. Retrospective and preclinical reports, case reports/series, reviews, and clinical studies not evaluating carfilzomib–immunomodulator combinations in NDMM were excluded based on review of titles and abstracts. A total of nine articles and 72 abstracts were deemed relevant and included in the review. A total of six distinct carfilzomib-based, PI/immunomodulator combination regimens have been evaluated in 12 clinical trials. Overall, treatment with these regimens has resulted in deep responses, including high rates of negativity for minimal residual disease. These deep responses have translated to long progression-free survival and overall survival rates. Efficacy results for these regimens have generally been consistent across subgroups defined by age, transplant eligibility, and cytogenetic risk. The safety profile of carfilzomib in NDMM is consistent with that observed in the relapsed-refractory MM setting. Clinical studies have found that carfilzomib-based combinations with immunomodulators are highly active with a favorable safety profile in NDMM. The carfilzomib, lenalidomide, and dexamethasone (KRd) drug backbone is a promising foundation for treatment strategies aimed at achieving long-term, deep responses (functional cures) in the frontline setting. Several ongoing studies are evaluating KRd, with or without anti-CD38 monoclonal antibodies.
Anti-idiotypic antibodies elicit anti-HIV-1–specific B cell responses
Authors: Pia Dosenovic, Anna-Klara Pettersson, Abigail Wall, Eddy S. Thientosapol, Junli Feng, Connor Weidle, Komal Bhullar, Ervin E. Kara, Harald Hartweger, Joy A. Pai, Matthew D. Gray, K. Rachael Parks, Justin J. Taylor, Marie Pancera, Leonidas Stamatatos, Michel C. Nussenzweig, Andrew T. McGuire
Journal: The Journal of Experimental Medicine (2019)

Human anti-HIV-1 broadly neutralizing antibodies (bNAbs) protect against infection in animal models. However, bNAbs have not been elicited by vaccination in diverse wild-type animals or humans, in part because B cells expressing the precursors of these antibodies do not recognize most HIV-1 envelopes (Envs). Immunogens have been designed that activate these B cell precursors in vivo, but they also activate competing off-target responses. Here we report on a complementary approach to expand specific B cells using an anti-idiotypic antibody, iv8, that selects for naive human B cells expressing immunoglobulin light chains with 5-amino acid complementarity determining region 3s, a key feature of anti-CD4 binding site (CD4bs)-specific VRC01-class antibodies. In mice, iv8 induced target cells to expand and mature in the context of a polyclonal immune system and produced serologic responses targeting the CD4bs on Env. In summary, the results demonstrate that an anti-idiotypic antibody can specifically recognize and expand rare B cells that express VRC01-class antibodies against HIV-1.
Progress in Testing for and Treatment of Hepatitis C Virus Infection Among Persons Who Inject Drugs — Georgia, 2018
Authors: Ketevan Stvilia, Philip R. Spradling, Alexander Asatiani, Maka Gogia, Khatuna Kutateladze, Maia Butsashvili, Jaba Zarkua, Tengiz Tsertsvadze, Lali Sharvadze, Maia Japaridze, Tinatin Kuchuloria, Lia Gvinjilia, Irinka Tskhomelidze, Amiran Gamkrelidze, Irma Khonelidze, David Sergeenko, Shaun Shadaker, Francisco Averhoff, Muazzam Nasrullah
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

In April 2015, the country of Georgia, with a high prevalence of hepatitis C virus (HCV) infection (5.4% of the adult population, approximately 150,000 persons), embarked on the world's first national elimination program (1,2). Nearly 40% of these infections are attributed to injection drug use, and an estimated 2% of the adult population currently inject drugs, among the highest prevalence of injection drug use in the world (3,4). Since 2006, needle and syringe programs (NSPs) have been offering HCV antibody testing to persons who inject drugs and, since 2015, referring clients with positive test results to the national treatment program. This report summarizes the results of these efforts. Following implementation of the elimination program, the number of HCV antibody tests conducted at NSPs increased from an average of 3,638 per year during 2006-2014 to an average of 21,551 during 2015-2018. In 2017, to enable tracking of clinical outcomes among persons who inject drugs, NSPs began encouraging clients to voluntarily provide their national identification number (NIN), which all citizens must use to access health care treatment services. During 2017-2018, a total of 2,780 NSP clients with positive test results for HCV antibody were identified in the treatment database by their NIN. Of 494 who completed treatment and were tested for HCV RNA ≥12 weeks after completing treatment, 482 (97.6%) were cured of HCV infection. Following the launch of the elimination program, Georgia has made much progress in hepatitis C screening among persons who inject drugs; recent data demonstrate high cure rates achieved in this population. Testing at NSPs is an effective strategy for identifying persons with HCV infection. Tracking clients referred from NSPs through treatment completion allows for monitoring the effectiveness of linkage to care and treatment outcomes in this population at high risk, a key to achieving hepatitis C elimination in Georgia. The program in Georgia might serve as a model for other countries.
Biochemotherapy versus chemotherapy for metastatic malignant melanoma: A meta-analysis of the randomised trials
Authors: N. J. Ives, R. L. Stowe, P. Lorigan, K. Wheatley
Journal: Journal of Clinical Oncology (2007)

8544 Background: Metastatic melanoma is associated with a poor survival rate. High response rates have been reported for both chemotherapy and biochemotherapy. To assess whether adding interferon-a (IFN) ± interleukin-2 (IL-2) to chemotherapy is advantageous, a published data meta-analysis of trials of biochemotherapy versus chemotherapy has been performed. Methods: Standard published data meta-analysis methods were used to assess response rates (partial, complete and objective (i.e. partial+complete)) and overall survival (OS), with odds ratios (OR) and 95% confidence intervals (CI) calculated. The only subgroup analysis performed was by type of immunotherapy, with trials divided according to the type of immunotherapy given in the biochemotherapy arm - IFN or IFN+IL-2. Results: Data were available from 18 trials (11 trials of chemotherapy ± IFN and 7 of trials chemotherapy ± IFN+IL-2). Nearly 2500 patients were included in the analysis, with 555 responses and 2,039 deaths observed. There was a clear benefit for biochemotherapy for partial response (OR=0.67, CI=0.54–0.83, p=0.0002), complete response (0.50, 0.35–0.73, p=0.0003) and objective response (0.60, 0.49–0.73, p&lt;0.00001). For objective response, these benefits were significant for both the IFN (0.60, 0.46–0.79, p=0.0002) and IFN+IL2 (0.60, 0.45–0.78, p=0.00002) subgroups. In contrast, there was no benefit on OS (0.99, 0.91–1.08, p=0.9), and there was also evidence of heterogeneity of treatment effect between the individual trials (p=0.006). Conclusions: This meta-analysis shows that biochemotherapy clearly improves response rates, but this does not appear to translate into a survival benefit. Single agent chemotherapy is considered the standard of care for the majority of patients receiving treatment for advanced melanoma outside a clinical trial, and the result of this meta-analysis shows no reason to change this. No significant financial relationships to disclose.