tbuckley/cabot-search huggingface dataset:
Generation and validation of a primary-tumor-derived four-gene prognostic signature for recurrence (R) of stages I/II colorectal cancer (CRC) following potentially curative resection
Authors: P. F. Lenehan, D. W. Fry, E. R. Heyman, J. F. Eliason, W. P. Worzel
Journal: Journal of Clinical Oncology (2009)

4035 Background: Current guidance for postoperative clinical management of stages I/II CRC patients (pts) is suboptimal. We hypothesized that a molecular prognostic test using primary CRC tissue would better predict the chances of tumor R within 3 years (y) than NCCN Clinical Practice Guidelines. Methods: Archival formalin-fixed paraffin-embedded (FFPE) primary adenocarcinoma tissues obtained at initial resection with curative intent were retrieved for 145 stage I/II (pT1–4 pN0 M0) CRC pts from multiple international sites; none had neoadjuvant or adjuvant therapy. Pts had tumor R by 36 months (mo) or confirmed non-recurrence (NR) for ≥36 mo after surgery. Pts were stratified by R/NR status and then randomized to a Training Set (TSet) (n=73; 34R, 39NR) or Validation Set (VSet) (n=72; 33R, 39NR). Tumor gene expression was quantified by DASL assay (Illumina, San Diego) using a custom 512-gene panel. Genetic programming (GP), a machine-learning technique, defined 15 TSet genes as key for differentiating pts with R versus NR. Results: Successive GP analyses of TSet data evolved a prognostic signature that mathematically combined 4 of the 15 key genes identified. This selected dichotomous rule correctly classified 28/33 R and 35/39 NR VSet pts (85% sensitivity, 90% specificity). ‘High risk’ pts had a significantly higher probability of R by 36 mo than ‘low risk’ pts: 88% PPV, 88% NPV; relative risk (RR) 7.0 (95% CI: 3.1, 16.1; p&lt;0.0001). RR by stage (I/II) = 7.00/7.28 and tumor site (colon/rectum) = 8.75/4.50. Kaplan-Meier recurrence-free survival: hazard ratio 11.8 (95% CI: 4.5, 31.1; p&lt;0.0001). NCCN Guidelines (V.2.2008) correctly classified 24/33 R and 15/39 NR VSet pts: 73% sensitivity, 38% specificity, 50% PPV, 63% NPV; RR 1.33 (95% CI: 0.74, 2.40; p=0.32). Conclusions: A GP derived 4-gene prognostic test using FFPE tumor tissue can differentiate early stage CRC pts at high versus low risk for R within 3y better than current NCCN Guidelines. [Table: see text] [Table: see text]
THU0134 Left ventricular (LV) diastolic dysfunction associates with systemic inflammation in rheumatoid arthritis (RA)
Authors: MJ Banks, F Ahmed, EJ Flint, PR Forsey, PA Bacon, GD Kitas
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Abnormal diastolic LV filling is an early marker of cardiovascular disease and death. In the general population, it associates with hypertension, LV hypertrophy or ischaemia. A high prevalence has been reported in RA and other inflammatory conditions (up to 40%), even after exclusion of patients with known, relevant cardiovascular pathology. Its cause and significance in inflammatory conditions remains unknown. <h3>Objectives</h3> To identify the causes of diastolic LV dysfunction in RA. <h3>Methods</h3> 39 random RA out-patients were assessed. LV filling: LV inflow Doppler in expiration by Echodoppler, with 5 measurements of isovolumetric relaxation time (IVRT), deceleration time (dte) and E:A ratio. Cardiac causes (BP, LVH, IHD ? age), Rose Questionnaire, examination, ECG, adenosine-stressed myocardial perfusion SPECT imaging. RA-related causes: acute phase response (current and mean ESR, CRP); cytokines (TNFa, Il-1b, Il-6); endothelial factors (vWF, ACE); Steroids: &gt;7.5 mg Prednisone for &gt;6 months; extra-articular disease. Statistics: Linear and multiple logistic regression as appropriate. <h3>Results</h3> Age correlated significantly with IVRT (r = 0.444, p = 0.005), dte (r = 0.495, p = 0.003), and E:A ratio (r = 0.67, p = 0.0001). Mean ESR correlated with IVRT (r = 0.324, p = 0.04), Mean CRP with E:A ratio (r = 0.305, p = 0.05), Il-6 with E:A ratio (r = 0.34, p = 0.05), vWF with IVRT (r = 0.346, p = 0.03) and E:A ratio (r = 0.331, p = 0.04). E:A ratio was significantly lower in those on steroids. Multiple regression showed age and mean ESR to independently predict IVRT. vWF was collinear with mean ESR for IVRT. Age, Il-6, and mean CRP were independent predictors of E:A ratio. vWF and steroids were collinear with mean CRP for E:A ratio. Hypertension, LVH, IHD, BMI, RA duration and extra-articular features did not associate with LV filling in RA. The association of LV filling with inflammatory mediators remained significant even after correction for age. <h3>Conclusion</h3> The association of worsening LV filling with inflammatory burden rather than established cardiovascular causes in RA is an interesting new observation. It may explain the previously reported high prevalence of abnormal LV filling in RA and other inflammatory conditions and may be due to direct cytokine effects on the myocardium.
Administrative Burden and Costs of Prior Authorizations in a Dermatology Department
Authors: Ryan P. Carlisle, Nicholas D. Flint, Zachary H. Hopkins, Mark J. Eliason, Kristina C. Duffin, Aaron M. Secrest
Journal: JAMA Dermatology (2020)

Insurance companies use prior authorizations (PAs) to address inappropriate prescribing or unnecessary variations in care, most often for expensive medications. Prior authorizations negatively affect patient care and add costs and administrative burden to dermatology offices.To quantify the administrative burden and costs of dermatology PAs.The University of Utah Department of Dermatology employs 2 full-time and 8 part-time PA staff. In this cross-sectional study at a large academic department spanning 11 clinical locations, these staff itemized all PA-related encounters over a 30-day period in September 2016. Staff salary and benefits were publicly available. Data were analyzed between December 2018 and August 2019.Proportion of visits requiring PAs, median administrative time to finalize a PA (either approval or denial after appeal), and median cost per PA type.In September 2016, 626 PAs were generated from 9512 patient encounters. Staff spent 169.7 hours directly handling PAs, costing a median of $6.72 per PA. Biologic PAs cost a median of $15.80 each and took as long as 31 business days to complete. The costliest PA equaled 106% of the associated visit's Medicare reimbursement rate. Approval rates were 99.6% for procedures, 78.9% for biologics, and 58.2% for other medications. After appeal, 5 of 23 (21.7%) previously denied PAs were subsequently approved.Prior authorizations are costly to dermatology practices and their value appears limited for some requests. Fewer unnecessary PAs and appeals might increase practice efficiency and improve patient outcomes.
Paclitaxel, ifosfamide, and cisplatin regimen as neoadjuvant chemotherapy in young women with locally advanced squamous cervical cancer
Authors: M. Marinaccio, E. De Marino, E. Mele, R. Catacchio, C. Pellegrino, V. Pinto, S. Schonauer
Journal: Journal of Clinical Oncology (2009)

5587 Background: Chemoradiotherapy is the standard treatment of advanced cervical cancer. Neoadjuvant chemotherapy (NAC) may represent an alternative for locally advanced cervical cancer (LACC).This study was undertaken to evaluate the efficacy of NAC in young patients with squamous LACC. Methods: Since 2000 to 2008, 61 pts (mean age 43 yrs) with squamous LACC were treated with NAC and afterwards evaluated for radical surgery. Eligibility included proven histologically diagnosis of squamous cervical carcinoma, FIGO stage IB2/IIA&gt;4cm/IIB, measurable disease, ECOG PS 0–2, no prior therapy and age under 49 years. All patients received TIP regimen (cisplatin 50 mg/m2 i.v. day 1, paclitaxel 175 mg/m2 over 3 hrs i.v.day1, ifosfamide 5,000 mg/m2 plus mesna 6,000 mg/m2 over 24 hrs i.v. day 1–2). Each cycle was repeated every 21 days. Patients were evaluated 4–6 weeks after the completion of the third cycle with the purpose to perform radical surgery according to clinical response. Results: 35pts (57.4%) were stage IB2; 9 (14.7%) were IIA &gt;4cm; and 17 (27.9%) were IIB. After restaging the clinical results were: CR = 4/61 (6.6%), PR = 51/61 (83.6%); no response = 5/61 (8.2%); progression = 1/61 (1.6%). A total of 55 pts (90.1%) were eligible for surgery; 6/61 pts (9.8%) were submitted to curative radiotherapy (until 2004) or chemoradiotherapy. Pathological responses after surgery were: 4 pCR (7.3%); 46 pPR (83.6%); and 5 (9.1%) pPR with presence of positive surgical margins or metastatic lymph nodes. Out of 55 pts, 50 received 2 cycles of TIP regimen as a consolidation therapy before follow-up; 5 pts with incomplete pPR underwent radio/chemoradiotherapy. After NAC an overall downstaging of LACC was obtained in 50/61 pts (82.0%). In this group of pts at the median follow-up of 42 months (range 4–98) updated as of December 2008, the 3-years progression-free survival and overall survival are 85.9% and 82.0%, respectively. Conclusions: Our results indicate that TIP regimen-based NAC is an attractive option in young women with squamous LACC (IB2,IIA &gt;4cm, IIB) that strongly desire surgery.The rate of patients with a prolonged remission of disease (82.0%) suggests that the clinical benefit of TIP regimen-based NAC followed by surgery may be comparable to chemoradiotherapy. No significant financial relationships to disclose.
Matteo Adinolfi: immunologist focusing on prenatal diagnosis of gene disorders
Authors: Rebecca Wallersteiner
Journal: BMJ (2020)

Matteo Adinolfi was born in 1928 in Asmara, Eritrea, to Attilio, a bank manager, and his wife, Maria (nee Sellitti), who had fled there from Italy to escape fascism. His father had been able to transfer to the bank’s Eritrean branch. Adinolfi remembered attending a local school with a handful of other Italian children and trips to the seaside. In his teens, he developed a lifelong passion for Russian novels. On a visit back to Naples in 1943, the family was trapped by the advancing war and unable to return to Africa. Attilio joined the navy. Matteo, his mother, and two sisters fled the bombing of Naples, taking shelter in the surrounding hillside. They fled from one hill to another, foraging for food, and finding shelter where they could. Matteo was half starved and severely ill with gastroenteritis; the experience motivated him to become a doctor.

Adinolfi read medicine at the University of Naples and worked there until 1962. In the same year, he moved to London and joined the haematology research unit at the Wright Fleming Institute, as well as practising at St Mary’s Hospital. In 1966 he was awarded his doctorate in immunology …
Personalizing treatment in early-stage breast cancer: The role of standard clinical factors and genomic information in adjuvant chemotherapy decision making
Authors: J. M. Gold, J. S. Najita, S. Lester, A. L. Richardson, D. E. Morganstern, W. Y. Chen, A. H. Partridge, I. E. Krop, E. P. Winer, H. J. Burstein
Journal: Journal of Clinical Oncology (2009)

572 Background: The Oncotype DX recurrence score (RS) independently predicts the likelihood of benefit from adjuvant chemotherapy. However, the clinical factors that influence chemotherapy recommendations in addition to RS are not well characterized. We sought to determine how clinicians integrate the RS and standard clinicopathologic data when choosing adjuvant chemotherapy. Methods: We identified women with ER+, HER2-, LN- breast cancer seen at DFCI in whom RS testing was performed between November 2004 and October 2008. Clinical and pathological characteristics, RS and chemotherapy treatment were identified from electronic medical records. A multivariable model was used to examine which factors drove the decision to administer chemotherapy. Results: RS was performed on 269 women with the following case distribution: RS low (&lt;18) 50%, RS intermediate (18–30) 41%, RS high (&gt;30) 9%. Chemotherapy was given to 7% of women with low RS, compared to 42% and 86% of women with intermediate and high RS, respectively. Tumor grade, T stage, progesterone receptor expression and RS were associated with receipt of chemotherapy in univariate analyses but age, LVI and menopausal status were not. In a multivariable logistic regression model, tumor grade, size, and RS were independent predictors of chemotherapy administration. Conclusions: Oncotype DX RS plays a critical role in medical decision making for women with early stage breast cancer at this single academic institution. However, other tumor and clinical features independently contribute to chemotherapy decisions, suggesting that tailored treatment does, and should, integrate both traditional and molecular pathological factors. [Table: see text] No significant financial relationships to disclose.
AB0056 The timing of low dose glucocorticoid therapy administration in treatment of rheumatoid arthritis
Authors: S Karatay, K Senel, M Ugur, K Yýldýrým
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> This study was performed to determine the effects of low dose prednisolone in treatment of rheumatoid arthritis (RA), administered in the morning or at night. <h3>Methods</h3> Thirty patients with active RA are divided randomly into two groups. For 6 months, a dosage of 7.5 mg/day prednisolone was administered at 02:00 am or 07:30 am to group I and group II respectively. In both groups, evaluations are performed between 07:30 – 08:00 am. During the treatment, changes observed each month in clinical and laboratory status of patients in both groups were recorded and results were compared both within and between the groups. <h3>Results</h3> Significant improvements were observed in both groups in morning stiffness, joint pain, Ritchie articular index, serum CRP and ESR levels compared to values before treatment, beginning from first month to sixth month (p &lt; 0.001). In the functional assessment; significant improvements were observed in both, determined beginning from the first month to sixth month compared to before treatment both in group receiving a night dose prednisolone and morning dose prednisolone (p &lt; 0.05). In comparison of morning stiffness, joint pain, Ritchie articular index and its functional assessment, and serum CRP and ESR levels in both groups, no significant difference was obtained from first month to sixth month (p &gt; 0.05). <h3>Conclusion</h3> Low dose prednisolone therapy in treatment of RA significantly suppresses the activity of disease beginning from the first month. This condition is kept until the sixth month. However, administration of the medication either given at morning hours classically or at night according to the diurnal rhythym of disease activity doesn?t affect the results of the treatment.
mRNA Delivery: Polymeric Nanocarriers with Controlled Chain Flexibility Boost mRNA Delivery In Vivo through Enhanced Structural Fastening (Adv. Healthcare Mater. 16/2020)
Authors: Takuya Miyazaki, Satoshi Uchida, Satoru Nagatoishi, Kyoko Koji, Taehun Hong, Shigeto Fukushima, Kouhei Tsumoto, Kazuhiko Ishihara, Kazunori Kataoka, Horacio Cabral
Journal: Advanced Healthcare Materials (2020)

In article number 2000538 by Horacio Cabral and co-workers, flexible catiomers fasten mRNA through efficient polyion complexation to form stable mRNA-loaded nanocarriers based on polyion complexation, resulting in enhanced protection against nuclease attack and polyanions toward increased translation both in vitro and in vivo and enhanced bioavailability of mRNA in blood. These results indicate polycation flexibility as a new approach to stabilize polyion complex for enhanced mRNA delivery.
Safety and efficacy of neratinib (HKI-272) in combination with paclitaxel in patients with solid tumors
Authors: L. Chow, Z. Jiang, R. Epstein, I. Bondarenko, A. Awada, C. Coughlin, E. Gauthier, Y. Zhao, R. Abbas, D. Hershman
Journal: Journal of Clinical Oncology (2009)

3557 Background: Neratinib (HKI-272) is a potent irreversible pan-ErbB inhibitor of the tyrosine kinase receptors, erbB-1,-2 and -4. In this phase 1 study, a combination dose of neratinib plus paclitaxel that is tolerable was determined in patients (pts) with solid tumors, and safety and preliminary efficacy were assessed in pts with erbB-2+ metastatic breast cancer. Methods: In this open label, 2-part study, ascending multiple daily oral doses of neratinib (160 mg, 240 mg) were administered in combination with IV paclitaxel 80 mg/m 2 , if tolerable, or 70 mg/m 2 on days 1, 8 and 15. Pts with solid tumors and pts with only metastatic erbB-2+ breast cancer are enrolled in part 1 and 2, respectively. Tumor measurements were made at screening and at every 8 weeks (2 cycles) by modified RECIST criteria. Timed blood samples were collected for neratinib and paclitaxel plasma concentration determination, and PK analyses were performed using a noncompartmental method. Results: Data for 54 pts as of 30 Oct 2008 are presented (median age [range] of 51.5 [20–74] yrs; 91% female; 26 % with prior trastuzumab treatment of median duration [range] 32.5 [10–52] wks; 15% with prior lapatinib treatment). Tumor types in part 1 included breast, endometrial, cervical, colorectal and esophageal cancer. There were no dose-limiting toxicities (DLTs) at the 240 mg neratinib-80 mg/m 2 paclitaxel dose, and as standard doses of neratinib and paclitaxel were reached, there was no reason for further escalation. Neratinib-related AEs, any grade in ≥10% of pts included diarrhea (50%), neutropenia (17%), rash (13%), nausea (11%) and vomiting (11%). Neratinib- related AEs, grade ≥3 in ≥2% of pts were diarrhea (20%), neutropenia (9%) and dehydration (4%). Only 2 pts (at the 240 mg neratinib-80 mg/m 2 paclitaxel dose) had dose reductions due to diarrhea. In 35 efficacy evaluable pts, 5 had confirmed partial response (PR). Confirmed clinical benefit (PR and prolonged disease stabilization) was seen in 2 pts in part 1, 1 pt with endometrial cancer and 1 pt with cervical cancer. Conclusions: This combination of 240 mg neratinib and 80 mg/m 2 paclitaxel was tolerable with a toxicity profile similar to that observed for neratinib, and had promising antitumor activity in pts with solid tumors and erbB-2 + breast cancer. [Table: see text]
Risk of noncompliance due to patient discomfort during screening mammogram
Authors: N. Mullai, N. Murugesan, L. Burton, V. Goodin, A. Stout
Journal: Journal of Clinical Oncology (2009)

1522 Background: There is enough evidence supporting the benefits of screening mammograms than any other screening procedure for the early detection of malignancy. Compliance to the screening method is very important to achieve this purpose. There is some concern about future trends in breast cancer mortality as a decline in rates of mammogram screening has been noticed. Pain during mammography has been recognized as a significant deterrent to breast screening. Hence this study was done to evaluate compliance in screening mammogram and to analyze major reasons for noncompliance. Methods: Randomly selected patients visiting the doctor's office for various reasons were asked about mammogram and their experience. Their responses were tabulated and analyzed statistically. Results: Out of 160 people questioned, 155 patients had mammogram regularly at 1–2 year interval and five patients did not. 50% of respondents were 51–70 years of age, 15% were 50 years or under, and 31% were over 70 years. Ninety patients (58%) reported their mammogram experience was unpleasant, causing pain and bruising. In spite of the discomforts reported, 132 (82.5%) patients said they would continue the screening as recommended. However, 28 patients (17.5%) indicated their intention not to get further mammograms based on their painful experience, unless the screening technology was improved. Conclusions: Breast cancer incidence after peaking in 1998 has decreased 9.8% since then with a 12% decline in women aged 50–60. The sharpest decline was noted from 2003 that could be due to the decrease in the hormone replacement therapy after the Women's Health Initiative report. However, it may also reflect some reduction in screening mammograms from 70% (in 2000) to 66% (in 2005) as estimated by National Health Interview Survey. Various causes were attributed for the decline in screening mammogram rate including the discomfort and pain caused by compression during film mammography. More than 1 in 6 patients refusing to undergo further screening is definitely a sign of concern. Better screening methods like patient controlled compression mammogram reported by Duke University Medical Center or other methods are worth investigating, to improve the compliance of the one of the effective preventive measures. No significant financial relationships to disclose.
Complications associated with erythropoietin stimulating agents (ESAs) in patients with metastatic breast cancer: A surveillance, epidemiology, and end results (SEER)–Medicare study
Authors: M. Chavez-Macgregor, S. Fang, T. P. Srokowski, G. N. Hortobagyi, S. H. Giordano
Journal: Journal of Clinical Oncology (2009)

1034 Background: Results of recent clinical trials suggest that the use of ESAs is associated with adverse outcomes. ESAs increase the risk for thrombotic events and have the potential of decreasing survival. Guidelines recommend the use of ESAs in patients with chemotherapy-induced anemia being treated with non curative intent. In this population-based study, we sought to evaluate the thromboembolic effects associated with the use of ESAs in patients receiving chemotherapy for metastatic breast cancer. Methods: Retrospective cohort study using the SEER-Medicare linked database. Patients with stage IV breast cancer diagnosed from 1995–2002, who were 66 and older, were treated with chemotherapy, and had full coverage of Medicare A and B were identified. Patients with end stage renal disease were excluded. ICD-9 and HCPCS codes were used to identify the use of ESAs, chemotherapy, comorbidities, and complications of therapy. Analyses were conduced using descriptive statistics, logistic regression, and Cox proportional hazard models. Results: 1411 women were included, 519 (36.8%) received ESAs and 892 (63.2%) did not; median age was 73 and 74 years old respectively. Median time from diagnosis to first ESA dose was 6 months, median number of ESAs doses was 8.5. In univariate analysis, patients receiving ESAs had higher rates of MI/CAD (38% vs 32.9% p = 0.051), thrombosis (32.4% vs 23.2% p = 0.0002), phlebitis (21.4% vs 12.6% p &lt; 0.0001), and transfusion (37.76% vs 19.4% p &lt; 0.0001), with no difference in the rate of stroke or pulmonary embolism. Multivariate analysis showed HR for MI/CAD 1.29 (1.01–1.66); thrombosis 1.5 (1.116–1.93), phlebitis 1.79 (1.32–2.43), and transfusion 2.65 (2.05–3.43). Significant dose effect was evident for the thrombosis and phlebitis outcomes for patients receiving more than 5 ESAs doses. Conclusions: The use of ESAs in patients with metastatic breast cancer increases the risk of thrombosis and phlebitis, with evidence of a dose-dependent effect. Patients receiving ESAs were more likely to have blood transfusions. These data support current practice of using ESAs for minimum necessary time to reduce risk of complications. No significant financial relationships to disclose.