tbuckley/cabot-search huggingface dataset:
Phase II comparative study of capecitabine combined with oxaliplatin (XELOX) and CPT-11 (XELIRI) for advanced colorectal cancer patients (p) previously treated with 5-FU-based chemotherapy
Authors: J. L. Manzano, N. Díaz, C. Rolfo, I. Juez, J. M. Gracía-Bueno, M. L. González, B. Queralt, F. Losa, C. Martín, A. Abad
Journal: Journal of Clinical Oncology (2007)

14544 Background: Based on the results obtained with Capecitabine (XEL), Oxaliplatin (OX), and CPT-11 (IRI), we proposed this exploratory study to asses the efficacy of XELIRI and XELOX, for advanced colorectal cancer, after a first line treatment with 5 FU plus OX (FOLFOX) or IRI (FOLFIRI). Methods: P aged = 18 with histological diagnosis of metastatic colorectal adenocarcinoma, were assigned to XELOX arm (XEL, 1000 mg/m 2 BID during 14 d; OX, 130 mg/m 2 d1; q3w) or XELIRI arm (XEL 1000 mg/m 2 BID during 14 d; IRI 240 mg/m 2 d1; q3w), depending on previous treatment (FOLFIRI or FOLFOX, respectively). Although sample size was calculated for 115 p, recruitment was premature closed due to the low inclusion rate related with cetuximab + IRI approval for second line treatment. Results: Forty three p (25 p, XELOX; 18 p, XELIRI) were enrolled: median age 63.2 years; M/F, 40.5%/59.5%; ECOG PS 0–1, 79.1%. All p have been previously treated for metastatic disease and 65.1% had stage IV. Main sites of metastatic disease were liver (71.8%), lymph nodes (7.7%), pelvis (7.7 %) and lung (5.1%). XELOX/XELIRI treatment data: total number of administered cycles was 94/85 and median relative dose intensity 100%(XEL)/99%(OX) and 96%(XEL)/94%(IRI); disease control rate (PR+SD) was 28%/33.3%, median TTP 3.4/4.1 months, median OS 10.3/11.2 months and 1-year survival, 39.1%/44.3%, respectively. Twenty p (46.5%) received further antitumoral treatment. Most frequent G3–4 toxicities per p are detailed in table 1 . Conclusions: Capecitabine based combinations show an excellent toxicity profile and good efficacy results, in terms of disease control and survival rates, for advanced colorectal cancer patients previously treated with 5-FU schedules. [Table: see text] No significant financial relationships to disclose.
Financial Eligibility Criteria and Medication Coverage for Independent Charity Patient Assistance Programs
Authors: So-Yeon Kang, Aditi Sen, Ge Bai, Gerard F. Anderson
Journal: JAMA (2019)

Although independent charity patient assistance programs improve patient access to costly prescription drugs, recent federal investigations have raised questions about their potential to increase pharmaceutical spending and to violate the federal Anti-Kickback Statute. Little is known about the design of the programs, patient eligibility, or drug coverage.To examine the eligibility criteria of the independent charity patient assistance programs and the drugs covered by them.Descriptive cross-sectional study of the 6 largest independent charities offering patient assistance programs for patients including, but not limited to, Medicare beneficiaries in 2018. These charities offered 274 different disease-specific patient assistance programs. Drugs were identified for subgroup analysis that had any use reported on the Medicare Part D spending dashboard and any off-patent brand-name drugs that incurred more than $10 000 in Medicare spending per beneficiary in 2016.Support by independent charity patient assistance programs.The primary outcomes were the characteristics of patient assistance programs, including assistance type, insurance coverage (vs uninsured), and income eligibility. The secondary outcomes were the cost of the drugs covered by the patient assistance programs and the coverage of expensive off-patent brand-name drugs vs substitutable generic drugs.Among the 6 independent charity foundations included in the analysis, their total revenue in 2017 ranged from $24 million to $532 million, and expenditures on patient assistance programs ranged from $24 million to $353 million, representing on average, 86% of their revenue. Of the 274 patient assistance programs offered by these organizations, 168 (61%) provided only co-payment assistance, and the most common therapeutic area covered was cancer or cancer treatment-related symptoms (113 patient assistance programs; 41%). A total of 267 programs (97%) required insurance coverage as an eligibility criterion (ie, excluded uninsured patients). The most common income eligibility limit was 500% of the federal poverty level. The median annual cost of the drugs per beneficiary covered by the programs was $1157 (interquartile range, $247-$5609) compared with $367 (interquartile range, $100-$1500) for the noncovered drugs. Off-patent brand-name drugs (cost: >$10 000) were covered by a mean of 3.1 (SD, 2.0) patient assistance programs, whereas their generic equivalents were covered by a mean of 1.2 (SD, 1.0) patient assistance programs.In 2018, among 274 patient assistance programs operated by the 6 independent charity foundations, the majority did not provide coverage for uninsured patients. Medications that were covered by the patient assistance programs were generally more expensive than those that were not covered.
Association of Urban Green Space With Mental Health and General Health Among Adults in Australia
Authors: Thomas Astell-Burt, Xiaoqi Feng
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Recent studies indicate that living near more green space may support mental and general health and may also prevent depression. However, most studies are cross-sectional, and few have considered whether some types of green space matter more for mental health. <h3>Objective</h3> To assess whether total green space or specific types of green space are associated with better mental health. <h3>Design, Setting, and Participants</h3> This cohort study included a residentially stable, city-dwelling sample of 46 786 participants from Sydney, Wollongong, and Newcastle, Australia, in the baseline of the Sax Institute's 45 and Up Study (data collected from January 1, 2006, to December 31, 2009). Follow-up was conducted from January 1, 2012, to December 31, 2015. Analyses were conducted in January 2019. <h3>Exposures</h3> Percentage of total green space, tree canopy, grass, and other low-lying vegetation measured within 1.6-km (1-mile) road network distance buffers around residential addresses at baseline. <h3>Main Outcomes and Measures</h3> Three outcome variables were examined at baseline (prevalence) and follow-up (incidence without baseline affirmatives): (1) risk of psychological distress (10-item Kessler Psychological Distress Scale), (2) self-reported physician-diagnosed depression or anxiety, and (3) fair to poor self-rated general health. <h3>Results</h3> This study included 46 786 participants (mean [SD] age, 61.0 [10.2] years; 25 171 [53.8%] female). At baseline, 5.1% of 37 775 reported a high risk of psychological distress, 16.0% of 46 786 reported depression or anxiety, and 9.0% of 45 577 reported fair to poor self-rated health. An additional 3.3% of 32 991 experienced psychological distress incidence, 7.5% of 39 277 experienced depression or anxiety incidence, and 7.3% of 40 741 experienced fair to poor self-rated health incidence by follow-up (mean [SD] of 6.2 [1.62] years later). Odds ratios (ORs) adjusted for age, sex, income, economic status, couple status, and educational level indicated that exposures of 30% or more total green space (OR, 0.46; 95% CI, 0.29-0.69) and tree canopy specifically (OR, 0.69; 95% CI, 0.54-0.88) were associated with lower incidence of psychological distress. Exposure to tree canopy of 30% or more, compared with 0% to 9%, was also associated with lower incidence of fair to poor general health (OR, 0.67; 95% CI, 0.57-0.80). Exposure to grass of 30% or more, compared with 0% to 4%, was associated with higher odds of incident fair to poor general health (OR, 1.47; 95% CI, 1.12-1.91) and prevalent psychological distress (OR, 1.71; 95% CI, 1.25-2.28). Exposure to low-lying vegetation was not consistently associated with any outcome. No green space indicator was associated with prevalent or incident depression or anxiety. <h3>Conclusions and Relevance</h3> Protection and restoration of urban tree canopy specifically, rather than any urban greening, may be a good option for promotion of community mental health.
LMO2 activation by deacetylation is indispensable for hematopoiesis and T-ALL leukemogenesis
Authors: Tatsuya Morishima, Ann-Christin Krahl, Masoud Nasri, Yun Xu, Narges Aghaallaei, Betül Findik, Maksim Klimiankou, Malte Ritter, Marcus D. Hartmann, Christian Johannes Gloeckner, Sylwia Stefanczyk, Christian Lindner, Benedikt Oswald, Regine Bernhard, Karin Hähnel, Ursula Hermanutz-Klein, Martin Ebinger, Rupert Handgretinger, Nicolas Casadei, Karl Welte, Maya Andre, Patrick Müller, Baubak Bajoghli, Julia Skokowa
Journal: Blood (2019)
Biomarq: A novel approach to automated HER2-analysis of circulating tumor cells (CTCs).
Authors: Aurelia Pestka, Thomas W. P. Friedl, Leonie Majunke, Bernadette Jaeger, Ulrich Andergassen, Julia Katharina Neugebauer, Julia Kathrin Jueckstock, Jan Keij, Klaus Friese, Tanja N. Fehm, Volkmar Mueller, Wolfgang Janni, Brigitte Kathrin Rack
Journal: Journal of Clinical Oncology (2013)

638 Background: Targeted treatment approaches directed against CTCs might improve the outcome of metastatic breast cancer patients. Accurate and reproducible assessment of the CTC phenotype is a requirement to use CTCs as treatment targets. The aim of this study was to test the suitability of the automated BioMarQ System (Veridex, USA) – an enhancement of the FDA-approved CellSearch System (Veridex USA) for CTC detection– for assessing the Her2-status of CTCs based on fluorescence and cell-morphology data. Methods: Data on classification of the Her2-status into four groups (0, +, ++, +++) obtained by visual inspection of CTCs after immunocytochemical staining with the CellSearch System, and of BioMarQ-generated automatic measures on fluorescence and cell morphology via image clips generated from raw images were available for 329 CTCs from 17 metastatic breast cancer patients. A discriminant analysis was performed to test whether linear combinations of the fluorescence and/or cell morphology measures allow a separation of CTCs into four groups according to the visual classification of their Her2-status. Results: The highest concordance with the visual classification was obtained by a set of three discriminant functions based on the five variables mean-, maximum- and integrated fluorescence intensity, cell area (µm 2 ), and coefficient of variation for the pixel fluorescence values within a cell. All five variables differed significantly among the 17 patients (Kruskal-Wallis-test, all p &lt; 0.001). Based on the three discriminant functions, 74.5% of all cases were correctly assigned to the four visually obtained categories (6 out of 8 CTCs classified as +++; 57 out of 80 as ++; 17 out of 65 as +, 165 out of 176 classified as 0). Conclusions: Our preliminary analysis shows that discriminant functions derived from measures on fluorescence and cell morphology generated by BioMarQ correctly assigned the Her2-status of CTCs to the four visually obtained categories in 75% of all cases. Further analysis based on a larger number of Her2-positive CTCs, and cross validation by FISH-analysis will provide deeper insight into the suitability of BioMarQ for objectively assessing the Her2-status of CTCs.
Erythropoiesis stimulating agent (ESA) administration at Hb &lt;10 g/dL for chemotherapy-induced anemia (CIA) following the National Coverage Decision (NCD)
Authors: S. A. Hulnick, G. Hess, J. Hill, H. N. Viswanathan, R. J. Nordyke
Journal: Journal of Clinical Oncology (2009)

e20627 Background: Medicare coverage of ESA treatment for CIA was changed in 7/07 to a hemoglobin (Hb) &lt; 10 g/dL prior to administration. We describe the proportion of ESA administrations at Hb &lt; 10 g/dL over four quarters following the NCD. Methods: A retrospective analysis of ESA administrations from 7/07 - 6/08 using Varian and Impac electronic medical records for 304,654 cancer patients from 91 practice sites across 19 states. Episodes of ESA treatment were identified within chemotherapy episodes. A &gt; 42 day gap in ESA use identified a completed ESA episode and a &gt; 90 day gap in chemotherapy identified a chemotherapy episode. Hb ≤ 7 days prior to ESA administration date was identified for each ESA episode. The percent of ESA administrations at Hb &lt; 10 g/dL was measured from Q3 07 to Q2 08 for darbepoetin alfa (DA) and epoetin alfa (EA) stratified by age. Results: For patients age ≥ 65, the percent of ESAs administered at Hb &lt; 10 g/dL increased from Q3 07 to Q2 08 for initial and maintenance administrations. A less pronounced trend was observed in patients age &lt; 65. Maintenance administrations at Hb &lt; 10 g/dL in patients age &lt; 65 were significantly lower for EA vs. DA. Conclusions: ESA administrations have been increasingly administered at Hb &lt; 10 g/dL. A higher proportion of Medicare-eligible patients received maintenance ESA administrations at Hb &lt; 10 g/dL. [Table: see text] [Table: see text]
Quality of care in advanced ovarian cancer: How important is provider specialty?
Authors: C. Mercado, D. Zingmond, B. Y. Karlan, E. Sekaris, J. Gross, M. Maggard-Gibbons, J. S. Tomlinson, C. Y. Ko
Journal: Journal of Clinical Oncology (2009)

e16519 Background: Ovarian cancer is one of the most aggressive and deadly cancers in women. While the mainstay of therapy is surgery, ovarian cancer surgical procedures are performed by surgeons with different specialty training, including gynecology, gynecologic oncology, general surgery, and others. We examine the degree to which surgeon specialty impacts survival and other quality of life-related outcomes in advanced ovarian cancer patients. Methods: Analyses of Stage 3c/4 ovarian cancer patients were performed from 4 states (California, Washington, New York, Florida). Four databases were linked for each state: cancer registry, inpatient-hospital discharge, AMA masterfile, and 2000 U.S. Census SF4 File. Multivariate modeling was performed to identify predictors of survival as well as proxy quality of life-related outcomes, as measured by creation of a fecal ostomy. Hospital case volume was defined as low volume (LV) [0–4 cases], middle volume (MV) [5–9], high volume (HV) [10–19], and very high volume (VHV) [20+]. Results: 60,405 ovarian cancer patients were identified; 53% were Stage 3c/4. Mean age was 64 years. Patients had lower hazard of death when treated in higher volume hospitals as compared to LV [HV (Hazard Ratio) HR = 0.89, p &lt; 0.0001; VHV HR = 0.79, p &lt; 0.001]. Patients treated by gynecologists/gynecologic-oncologists had lower hazard of death (HR = 0.61, p &lt; 0.0001) as compared to other surgeons (non-gynecologist), controlling for hospital type, case volume, comorbidity, and demographics. Also, patients treated by a trained gynecologist had the lowest chance of having an ostomy performed as compared to those of other specialties (HR = 0.22, p &lt; 0.0001). Factors associated with receiving treatment from a non-gynecologist included low volume, rural patient residence, poverty, and high comorbidity. Conclusions: Stage 3c/4 ovarian cancer patients have better survival when treated by gynecology-trained surgeons. Our data suggest that gynecology-trained specialists optimize quality of life-related outcomes, specifically minimizing the creation of a fecal ostomy. Surgeon specialty was more important than procedure volume for these outcomes. Referral to gynecology-trained surgeons would improve survival and quality of life outcomes in advanced ovarian cancer patients. No significant financial relationships to disclose.
RIPK1 gene polymorphism as a prognostic marker for survival in patients with colorectal cancer
Authors: Y. Chae, J. Kim, S. Sohn, S. Kim, S. Lee, J. Moon, S. Jeon, Y. Cho, G. Choi, S. Jun
Journal: Journal of Clinical Oncology (2009)

e15078 Background: Since apoptosis plays a key role in cancer progression, we hypothesized that single nucleotide polymorphisms (SNPs) of apoptosis-related gene can affect survival after curative resection in patients with colorectal cancer. Patients and Methods: Three hundred and ninety seven patients with colorectal cancer who underwent surgery with curative intent were enrolled in the present study. The genomic DNA was extracted from fresh colorectal mucosal tissue, and the 19 SNPs of 15 apoptosis-related genes (CASP3, CASP6–10, FAS, FAS ligand [FASLG], TNSFR1A, TNSFR10B, RIPK1, BCL2, BCL2 ligand [BCL2L], TP53, and PTGS2) were determined using a PCR-RFLP assay. Results: The median age of the patients was 63 years (range, 21–85), and 218 (54.9%) patients had colon cancer and 179 (45.1%) patients rectal cancer. Pathologic stages after surgery were as follows: stage 0/I (n=86, 21.7%), stage II (n=146, 36.8%), stage III (n=145, 36.5%), and stage IV (n=20, 5.0%). Multivariate survival analysis including pathologic stage, differentiation, age, and CEA level showed that relapse-free survival for the patients with the GA+AA genotype of RIPK1 (Receptor interacting serine/threonine kinase 1) +83G&gt;A (rs2272990) was worse than for the patients with the GG genotype (hazard ratio [HR]=1.66, 95% confidence interval [CI]=1.03–2.68, p=0.038). However, no associations were observed between the polymorphisms and overall survival (OS) in a multivariate analysis. Conclusions: RIPK1 gene polymorphism can be considered as a possible prognostic marker for survival after curative resection in patient with colorectal cancer. No significant financial relationships to disclose.
Temozolomide metronomic schedule with weekly of cisplatin in metastaticsoft tissue sarcoma.
Authors: Tanweer Shahid, Vikash Agarwal, Saumen Basu, Gouri Shankar Bhattacharyya
Journal: Journal of Clinical Oncology (2013)

e21519 Background: Dacarbazine (DTIC) is the standard treatment for metastatic soft tissue sarcoma. Temozolomide (TMZ) is a potentially attractive chemotherapeutic agent for this disease because of the oral route of administration and efficacy similar to that of dacarbazine but potential for resistance exist. Metronomic administration of TMZ might be a way to overcome resistance. Cisplatin is active against melanoma and might counteract mechanisms of resistance to TMZ. Methods: We reviewed data of metastatic soft tissue sarcoma patients treated at our Institutions with cisplatin (25 mg/m 2 every 7 days for 3 out of 4 weeks) plus TMZ (50 mg/m 2 /day from day 2 for 27days). Our practice included such scheme for patients younger than 75 years, with a performance status not worse than 2, and adequate bone marrow, liver and renal function. Assessment of response was done every 3 cycles. Toxicity was graded according to NCI-CTC. Results: From August 2007 to September 2008, 33 patients were treated with a median age of 44 years (18–74); most frequent sites of metastases were lung (18 cases), brain and lymph nodes (11 cases each); 29 patients were treated as first-line and 4 as second-line. The median number of delivered cycles was 4 (range 2- 8). Toxicity was mild, with no grade 4 event reported. Nausea and vomiting were the most frequent and severe toxic effects: grade 3 in 2 cases and grade 2 in 10 cases, respectively. Other toxicities included thrombocytopenia (1 case grade 3 and 2 cases grade 2), anemia (1 grade 3 and 2 grade 2), neutropenia, and fatigue (1 grade 3 each). Overall, 9 patients had a partial response (27.3%; 95% exact CI: 7.0–35.5) and 8 (24%) had a disease stabilization. With a median follow-up of 20 weeks (95% CI: 19–57), there were 19 progressions and a median progression-free survival of 24 weeks (95% CI: 16-nr); 9 patients died with a median survival of 50 weeks (95% CI 43-nr). Conclusions: Results obtained in clinical practice with metronomic temozolomide plus cisplatin in the treatment of patients with metastatic soft tissue sarcoma are encouraging, in light of the negative prognostic features of treated patients.
Early Paraprotein Kinetics and Response to Treatment in Multiple Myeloma
Authors: Binder Moritz, S. Vincent Rajkumar, Martha Q Lacy, Morie A. Gertz, Francis K Buadi, Angela Dispenzieri, Yi L. Hwa, Amie Fonder, Miriam Hobbs, Suzanne R. Hayman, Steven Zeldenrust, John A. Lust, Stephen J. Russell, Nelson Leung, Prashant Kapoor, Ronald S. Go, Wilson I Gonsalves, Taxiarchis Kourelis, Rahma Warsame, Robert A Kyle, Shaji K Kumar
Journal: Blood (2017)
The emerging role of mast cell proteases in asthma
Authors: Gunnar Pejler
Journal: European Respiratory Journal (2019)

It is now well established that mast cells (MCs) play a crucial role in asthma. This is supported by multiple lines of evidence, including both clinical studies and studies on MC-deficient mice. However, there is still only limited knowledge of the exact effector mechanism(s) by which MCs influence asthma pathology. MCs contain large amounts of secretory granules, which are filled with a variety of bioactive compounds including histamine, cytokines, lysosomal hydrolases, serglycin proteoglycans and a number of MC-restricted proteases. When MCs are activated, e.g. in response to IgE receptor cross-linking, the contents of their granules are released to the exterior and can cause a massive inflammatory reaction. The MC-restricted proteases include tryptases, chymases and carboxypeptidase A3, and these are expressed and stored at remarkably high levels. There is now emerging evidence supporting a prominent role of these enzymes in the pathology of asthma. Interestingly, however, the role of the MC-restricted proteases is multifaceted, encompassing both protective and detrimental activities. Here, the current knowledge of how the MC-restricted proteases impact on asthma is reviewed.
Sex differences in cardiac function, biomarkers and exercise performance in heart failure with preserved ejection fraction: findings from the RELAX trial
Authors: Rina Mauricio, Kershaw V. Patel, Vijay Agusala, Kavisha Singh, Alana Lewis, Colby Ayers, Justin L. Grodin, Jarett D. Berry, Ambarish Pandey
Journal: European Journal of Heart Failure (2019)