tbuckley/cabot-search huggingface dataset:
Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients
Authors: Randall C. Starling, Jerry D. Estep, Douglas A. Horstmanshof, Carmelo A. Milano, Josef Stehlik, Keyur B. Shah, Brian A. Bruckner, Sangjin Lee, James W. Long, Craig H. Selzman, Vigneshwar Kasirajan, Donald C. Haas, Andrew J. Boyle, Joyce Chuang, David J. Farrar, Joseph G. Rogers
Journal: JACC Heart Failure (2017)

The authors sought to provide the pre-specified primary endpoint of the ROADMAP (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients) trial at 2 years.The ROADMAP trial was a prospective nonrandomized observational study of 200 patients (97 with a left ventricular assist device [LVAD], 103 on optimal medical management [OMM]) that showed that survival with improved functional status at 1 year was better with LVADs compared with OMM in a patient population of ambulatory New York Heart Association functional class IIIb/IV patients.The primary composite endpoint was survival on original therapy with improvement in 6-min walk distance ≥75 m.Patients receiving LVAD versus OMM had lower baseline health-related quality of life, reduced Seattle Heart Failure Model 1-year survival (78% vs. 84%; p = 0.012), and were predominantly INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profile 4 (65% vs. 34%; p < 0.001) versus profiles 5 to 7. More LVAD patients met the primary endpoint at 2 years: 30% LVAD versus 12% OMM (odds ratio: 3.2 [95% confidence interval: 1.3 to 7.7]; p = 0.012). Survival as treated on original therapy at 2 years was greater for LVAD versus OMM (70 ± 5% vs. 41 ± 5%; p < 0.001), but there was no difference in intent-to-treat survival (70 ± 5% vs. 63 ± 5%; p = 0.307). In the OMM arm, 23 of 103 (22%) received delayed LVADs (18 within 12 months; 5 from 12 to 24 months). LVAD adverse events declined after year 1 for bleeding (primarily gastrointestinal) and arrhythmias.Survival on original therapy with improvement in 6-min walk distance was superior with LVAD compared with OMM at 2 years. Reduction in key adverse events beyond 1 year was observed in the LVAD group. The ROADMAP trial provides risk-benefit information to guide patient- and physician-shared decision making for elective LVAD therapy as a treatment for heart failure. (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients [ROADMAP]; NCT01452802).
Cost identification of an individualized dosing strategy for lutenizing hormone releasing hormone agonist (LH-RHa) in the treatment of hormone refractory prostate cancer (HRPC)
Authors: J. A. Wagmiller, A. W. Dick, D. M. Sahasrabudhe
Journal: Journal of Clinical Oncology (2004)

4588 Background: LH-RHa are administered on a fixed schedule (1, 3, or 4 month intervals) without adjustment for patient characteristics. Recent data indicate that in many men testosterone remains suppressed significantly longer than 3 or 4 months and that resuming LH-RHa when testosterone reaches a threshold level (individualized LH-RHa dosing) may be feasible and cost effective. Methods: We performed a formal analysis to determine the costs associated with orchiectomy, standard tri-monthly LH-RHa dosing and individualized LH-RHa dosing. We considered men with metastatic prostate cancer, newly found to be hormone refractory. The model used a societal perspective, a time horizon of 5 years, 3% annual cost discounting and accounted for costs of surgery, testosterone monitoring, antiandrogen, LH-RHa, and LH-RHa administration. We assumed average 6-month duration of castrate testosterone after stopping LH-RHa and equal life expectancy for the three methods. We assumed the prevalence for HRPC would equal the annual death rate from prostate cancer (30,200), which we think underestimates the population to which the results of this analysis could be applied. Results: Lifetime individual and population costs after prostate cancer becomes hormone refractory are given in the table. Conclusion: Compared with standard dosing of LH-RHa, individualized LH-RHa dosing in men with HRPC appears to be associated with moderate savings on an individual basis but significant savings on a population basis. Individualized LH-RHa dosing is more costly than orchiectomy, but assuming a standard societal cost of $50,000 per quality adjusted life year (QALY), even a patient preference of 0.08 QALY in favor of medical over surgical androgen ablation would make individualized LH-RHa dosing a cost effective choice. No significant financial relationships to disclose.
RESTRICTION IN HIP INTERNAL ROTATION AND 5TH METATARSAL STRESS FRACTURES (JONES FRACTURE) IN PROFESSIONAL FOOTBALL PLAYERS
Authors: Yoshitomo Saita, Masashi Nagao, Yohei Kobayashi, Keiji Kobayashi, Hiroshi Ikada
Journal: British Journal of Sports Medicine (2017)

Background Fifth metatarsal stress fracture (Jones fracture) is one of the issues of sports-related injuries. Objective Exploration of unknown risk factor for developing Jones fractures. Design Case control study. Setting Retrospective cohort study in male Japanese professional football (soccer) players. Patients (or Participants) Case control study conducted between with (n=20) and without (n=40) the history of Jones fractures. Interventions (or Assessment of Risk Factors) Reviewed the medical check data regarding the joint and muscle tightness at the time they joined the team, and compared them between two groups. Main Outcome Measurements Risk factors to develop developing Jones fracture. Results The mean age sustaining Jones fracture was 20.5 years old (95% CI, 19.1–21.8, range 17–28). The fracture occurred in their non-dominant (standing) legs in 60% (12/20) of players. Among the physical examination data, Hip internal rotation (HIR) was significantly restricted in players with history of Jones fracture (25.9 degrees on average) compared with those without Jones fractures (40.4 degrees, p&lt;0.0001). Logistic regression demonstrated that the wider range of HIR was associated with a statistically significantly decreased odds of Jones fracture (OR=0.83, 95% CI=0.75–0.91), while other physical examination data were not significant. A post-estimation analyses demonstrated that a 10-degree reduction in HIR of the right hip significantly increased the odds of Jones fracture in ipsilateral or contralateral foot (OR=3.11, 95% CI=1.35–7.16, and OR=2.24, 95% CI=1.22–4.12, respectively). Similarly, a reduction in HIR of the left hip significantly increased the odds of Jones fracture in ipsilateral or contralateral foot (OR=2.77, 95% CI=1.08–7.08, and OR=4.88, 95% CI=1.56–15.28, respectively). Conclusions Restriction of HIR was significantly associated with increased risk of Jones fracture in professional football players in Japan.
Docetaxel as adjuvant therapy on patients with locally advanced breast cancer (LABC), after neoadjuvant chemotherapy with anthracyclines followed by radical surgery +/− radiotherapy
Authors: E. E. Franco, J. A. Silva, M. Perez, M. Silva, R. Villalobos, S. Labastida, G. Olivares, A. L. Castruita
Journal: Journal of Clinical Oncology (2004)

743 Background:The aim was to determine the benefit in Disease Free Survival (DFS) and Overall Survival (OS) of the docetaxel as adjuvant therapy LABC after multimodal therapy. Methods:761 patients with diagnosis of breast cancer were revised. 130 patients met criteria with stages II-B (T3N0M0), III-A, III-B, III-C that received treatment from Jan 1999 to March 2003. Combined modality consisted on a first phase with neoadjuvant chemotherapy (NCT) with anthracyclines, followed by Radical Mastectomy (RM) +/- Radiotherapy and Docetaxel for 4 cycles as adjuvant therapy. Results:51.5% had Stage III-A and 40% III-B,8.5% other (IIb, IIIC). 83.1% received 4 cycles of NCT (median of 4, range of 3 to 6). 127 patients (97.6%) received radiotherapy, 31 in preoperative manner and 96 postoperative. 95.4% underwent RM. Only 3.9% treated with conservative surgery. The median follow-up was 26.5 months (range 9–55 months). The DFS at 36 months was 60% (+/-7.8%) and the OS at 48 months was 71.52% (+/- 8.9%). The OS at 36 months for the patients with node negative(N-) disease was 100% and 74.2% (+/-14.4%), 74.9% (+/-9%) and 69%(+/-14.1%) for the group of 1–3, 4–9 and >10 axillary positive nodes (N+)respectively. There was a statistically significant difference between the group of N- and 4–9 (p = 0.029) and between the N- group and the >10 (p = 0.041). The OS at 36 months according to the estrogen receptors status was 85.47% (+/-6.7%) for negative receptors and 96.97% (+/-2.9%) for the positive ones (p = 0.02). The Cox model demonstrated that the most important factor that increases the risk of death was the number of N+ (p = 0.05). There were not statistically significant differences in the analysis according to the different clinical stages, pathological tumor size, histology, menopausical state, HER-2/neu expression neither vasculo/lymphatic permeation. Conclusions:Results suggest that adjuvant chemotherapy with 4 cycles of docetaxel as part of the multimodal therapy in LABC could benefit this group of patients, however it is necessary a longer follow-up in order to know the real impact in survival. No significant financial relationships to disclose.
Modulation of the Vitamin D3 Response by Cancer-Associated Mutant p53
Authors: Perry Stambolsky, Yuval Tabach, Giulia Fontemaggi, Lilach Weisz, Revital Maor-Aloni, Zahava Siegfried, Idit Shiff, Ira Kogan, Moshe Shay, Eyal Kalo, Giovanni Blandino, Itamar Simon, Moshe Oren, Varda Rotter
Journal: Cancer Cell (2010)
A phase II clinical and translational study of MK-2206 in patients with metastatic neuroendocrine tumors (NETs).
Authors: Diane Lauren Reidy, Maria Catherine Pietanza, Michal Segal, Marinela Capanu, Leonard Saltz
Journal: Journal of Clinical Oncology (2013)

e15133 Background: Up-regulation of the phosphoinositide-3 phosphate kinase (PI3K) pathway is associated with poor prognosis in NET cell lines. In patients treated with mTOR inhibitors, up-regulation of AKT may be a key driver in development of resistance. We hypothesized that blockade of AKT in patients with refractory NETs would result in eliminating one of the key drivers of tumor growth and prolong PFS. We evaluated the safety and efficacy of MK-2206, an orally active, allosteric Akt inhibitor of human Akt1, Akt2, and Akt3 as monotherapy in metastatic well differentiated progressive neuroendocrine patients. Methods: A phase II study was performed in which patients received MK-2206 at a dose of 200 mg PO once weekly. Archived pretreatment tumor tissue was obtained for putative biomarkers. Results: The study terminated early on the basis of a business decision by the sponsor. Eight patients were treated (6 carcinoid, 2 pNET); female, 25%; median age, 58.5 years, range 66-25). There were no complete or partial responses. 1 patient (atypical thymic carcinoid with brain metastases refractory to all standard therapies including mTOR and VEGF inhibitors) experienced a 17% decrease in tumor size (SD) for over 10 months and an additional 3 patients had SD for 12 weeks or longer by RECIST 1.0 (4/8, 50%; range 4.2-10.2 months). The most common grade 3 adverse events potentially related to MK-2206 were hyperglycemia (3 pts, 37.5%), elevated liver function tests (3 pts, 37.5%), and rash (3 pts, 37.5%). There were no serious adverse events (SAEs) related to MK-2206. Tumor from the patient with greatest radiographic response was evaluated by next generation sequencing, which failed to identify mutations in the AKT pathway (i.e., PTEN, AKT, and PI3KCA). Conclusions: MK-2206 alone was well tolerated, except for hyperglycemia, transaminitis, and rash, all of which were manageable. Although the study was incomplete, evidence of antitumor response in a refractory carcinoid tumor is of interest. Further evaluation of agents targeting AKT and/or PI3K are warranted in NETS. Preclinical studies are ongoing to better define a potential targeted population. Clinical trial information: NCT01169649.
Androgen receptor (AR) amplification in patients (pts) with metastatic castration resistant prostate cancer (mCRPC) resistant to abiraterone (Abi) and enzalutamide (Enz): Preliminary results from the SU2C/PCF/AACR West Coast Prostate Cancer Dream Team (WCDT).
Authors: Rahul Raj Aggarwal, George Thomas, Jack Youngren, Adam Foye, Susan Olson, Pamela Paris, Tomasz M. Beer, Charles J. Ryan, Owen Witte, Christopher P. Evans, Martin Edwin Gleave, Josh Stuart, Joshi J. Alumkal, Alexandria Toschi, Nicole Zona, Robert Evan Reiter, Primo Lara, Kim N. Chi, Eric Jay Small
Journal: Journal of Clinical Oncology (2015)

5068 Background: Mechanisms of resistance to Abi or Enz in mCRPC pts are poorly understood. AR amplification (AR amp) is observed in Abi/Enz naive mCRPC pts, but its role in mCRPC pts who develop resistance to Abi/Enz is not known. As part of the WCDT project, which aims to identify genetic pathways underlying resistance to Abi and Enz, AR amp status was assessed in metastatic tumor biopsies from mCRPC pts. Methods: Eligible mCRPC pts underwent biopsy (bx) at one of 5 WCDT sites, using a uniform bx and clinical follow-up protocol. Formalin fixed, paraffin-embedded tissue underwent pathologic review and fluorescence in situ hybridization (FISH) for assessment of AR amp in a CLIA laboratory. AR amp by FISH was corroborated with array comparative genomic hybridization (aCGH) in select cases. Results: 150 mCRPC pts have undergone bx to date. To date, 92 have been evaluated by FISH for AR amp, including 36 from bone, 35 from lymph nodes, 16 from liver, and 5 from other soft tissues. Overall, 64% of mCRPC tumors were AR amplified by FISH and were corroborated by aCGH in 16/21 cases (76%). AR amp was seen in similar proportions in liver, bone, or nodal bx, and was present in > 50% of tumors with small cell histology. AR amp was observed in 16/19 pts (84%) naïve to both Abi + Enz compared to 17/36 pts (47%) who were resistant to Abi (p = 0.008). 4/6 (67%) of Enz resistant tumor biopsies were AR amplified. In pts that received Abi or Enz post-bx, the PSA response rate (PCWG2 criteria) was 9/17 (53%) in AR amp and 5/12 (42%) in AR non-amplified tumors respectively. Conclusions: AR amplification status can be assessed by FISH from mCRPC biopsies. AR amplification was common in Abi/Enz-naïve tumors including those with small cell histology. AR amp was less frequent in pts with Abi resistance, suggesting that Abi may select for non-AR amplified cells. Sequential (paired) biopsies from the same pts are being evaluated to test this hypothesis. Preliminary data suggest higher rates of AR amp in pts who are resistant to Enz. The predictive utility of AR amp status and AR splice variants is currently being evaluated.
Association of Insurance Expansion With Surgical Management of Thyroid Cancer
Authors: Andrew P. Loehrer, Shilpa S. Murthy, Zirui Song, Carrie C. Lubitz, Benjamin C. James
Journal: JAMA Surgery (2017)

To our knowledge, thyroid cancer incidence is increasing faster than any other cancer type and is currently the fifth most common cancer among women. While this rise is likely multifactorial, there has been scarce consideration of the effect of insurance statuses on the treatment of thyroid cancer.We evaluate the association of insurance expansion with thyroid cancer treatment using the 2006 Massachusetts health reform, which serves as a unique natural experiment.We used the Agency for Healthcare Research and Quality State Inpatient Databases to identify patients with government-subsidized or self-pay insurance or private insurance who were admitted to a hospital with thyroid cancer and underwent a thyroidectomy between 2001 and 2011 in Massachusetts (n = 8534) and 3 control states (n = 48 047). Difference-in-differences models were used to evaluate an association between the 2006 Massachusetts health care reform and thyroid cancer treatment, and participants were controlled for age, sex, comorbidities, and secular trends.Change in the thyroidectomy rate for thyroid cancer treatment was the primary outcome evaluated.The Massachusetts cohort consisted of 6443 women (75.5%) and 2091 men (24.5%), of whom 6388 (79.6%) were white, 391 (4.9%) were black, 527 (6.6%) were Hispanic, 424 (5.3%) were Asian/Pacific Islander, 63 (0.8%) were Native American, and 228 (2.8%) were other. The participants from control states included 36 818 women (76.6%) and 11 229 men (23.4%), of whom 30 432 (65.5%) were white, 3818 (8.2%) were black, 6462 (13.9%) were Hispanic, 2591 (5.6%) were Asian/Pacific Islander, 211 (0.5%) were Native American, and 2947 (6.3%) were other. Before the 2006 Massachusetts insurance expansion, patients with government-subsidized or self-pay insurance had lower thyroidectomy rates for thyroid cancer in Massachusetts and the control states compared with patients with private insurance. The Massachusetts insurance expansion was associated with a 26% increased rate of undergoing a thyroidectomy (incident rate ratio, 1.26; 95% CI, 1.04-1.52; P = .02) and a 22% increased rate of neck dissection (incident rate ratio, 1.22; 95% CI, 1.07-1.37; P = .002) for treating cancer compared with control states.The 2006 Massachusetts health reform, which is a model for the Affordable Care Act, was associated with a 26% increased rate of thyroidectomy for treating thyroid cancer. Our study suggests that insurance expansion may be associated with increased access to the surgical management of thyroid cancer. Further studies need to be conducted to evaluate the effect of healthcare expansion at a national level.
Study of serum EGFR, HER-2/neu,VEGF in metastatic breast cancer patients treated with taxanes
Authors: S. V. Labropoulos, G. Fountzilas, S. Papadopoulos, M. Karina, M. Xylouri, A. Doudoulakakis, S. Chalkidou, E. D. Razis
Journal: Journal of Clinical Oncology (2004)

757 Background: Novel drugs with activity against EGFR,Her-2/neu,VEGF are used in clinical practice. Previous studies have examined the possible prognostic and predictive role of soluble EGFR, Her-2/neu,VEGF, in metastatic breast cancer(MBC) with various results.We examine whether their combined measurement has any prognostic or predictive role. Methods: Retrospective analysis of frozen serum from women with MBC who received first line taxane based chemotherapy. Analysis was performed centrally with the use of commercially available ELISA. Specifically for EGFR and Her-2/neu a Microtiter ELISA (Bayer Diagnostics) and for VEGF a Microliter ELISA (R &D System). Normal values were calculated according to previous published literature. Results: Demographics: Total 41 women with a median age of 54, 54% premenopausal,51% postmenopausal,61% were ER positive 39% negative. Serum was drawn prior to chemotherapy. All patients received first line treatment: 22 Paclitaxel /Epirubicin,8 Paclitaxel /Carboplatin,8 Paclitaxel /Trastuzumab,3 Paclitaxel/Gemcitabine/Trastuzumab. Complete response had 10% partial response 49%.After a median follow-up of 46,7(3,2–62,8) months 38 patients have relapsed and 28 have died yielding a median TTP of 13,4 mo and a median OS of 34,8 mo. EGFR was abnormal in 51%,Her-2/neu in 61% and VEGF in 54%. 6/41 patients over-expressed all three markers and 7/41 none. OS was statistically worse for patients who had all abnormal (p=0.027 long rank) compared to those with all normal with median overall survival of 44,1 vs 10 months. Elevated Her-2/neu and elevated VEGF showed a trend for decreased OS ( p=0.0564,p=0.0519 respectively ). Patients with abnormal Her-2/neu who received trastuzumab based therapy had a better TTP (p=0.043). Conclusions: In this small retrospective analysis the group of MBC patients with elevated serum EGFR, Her -2/neu and VEGF seem to have a worse prognosis and trastuzumab based therapy seems to benefit patients with abnormal serum Her-2/neu level. Further study in larger groups of patients with MBC is warranted along with serial measurement during targeted therapy. No significant financial relationships to disclose.
FGF21 Regulates Metabolism Through Adipose-Dependent and -Independent Mechanisms
Authors: Lucas D. BonDurant, Magdalene Ameka, Meghan C. Naber, Kathleen R. Markan, Sharon O. Idiga, Michael R. Acevedo, Susan A. Walsh, David M. Ornitz, Matthew J. Potthoff
Journal: Cell Metabolism (2017)
Rate of use of NCCN “preferred” chemotherapy regimens for the treatment of HER2 positive breast cancer.
Authors: Eric J. Gratias, Margaret Rausa, Lee N. Newcomer, Kurt Andrews, Nick Andrews, Richard B. Weininger
Journal: Journal of Clinical Oncology (2017)

163 Background: The National Comprehensive Cancer Network (NCCN) Guidelines represent a well-established standard of care for the treatment of HER2+ breast cancer patients. eviCore healthcare is a licensee of NCCN that uses the NCCN guidelines to support its proprietary chemotherapy management program. All regimens assigned NCCN Category of Evidence 1, 2A, or 2B are adherent treatments in the eviCore program. NCCN recommends many systemic treatment options for HER2+ breast cancer, and a limited group is designated by NCCN as “preferred” based on superior efficacy and/or safety. This study evaluated the frequency of NCCN-preferred regimen use by practicing oncologists in HER2+ breast cancer patients. Methods: Chemotherapy authorizations for all HER2+ breast cancer patients with ≥ 1 injectable drug from 4/1/2015-9/30/2016 for multiple payers were included; &gt; 90% of authorizations occurred in United HealthCare members. Cases with incomplete data were excluded. 3685 fully evaluable cases were stratified by stage, ER/PR status, and NCCN-preferred vs. NCCN-recommended status. The frequency of NCCN-preferred regimen selection was calculated for each subgroup. Results: There were 2883 HER2+/ER+ and/or PR+ cases and 802 HER2+/ER-/PR- cases. The highest frequency of NCCN-preferred regimen use occurred in neoadjuvant chemotherapy for patients with Stage III HER2+/ER+ and/or PR+ disease, where 88% of 289 patients used an NCCN-preferred regimen. Metastatic HER2+ patients had a markedly lower rate of NCCN-preferred regimen use at 62% of 557 cases. Only 48% of 1096 patients with Stage I/II HER2+/ER+ and/or PR+ disease received NCCN-preferred regimens. Conclusions: Patients receiving neoadjuvant chemotherapy for HER2+ breast cancer receive NCCN-preferred regimens at significantly higher rates than patients receiving adjuvant chemotherapy or metastatic treatment. Less than half of patients receiving adjuvant chemotherapy are receiving NCCN-preferred regimens. Further study is needed to determine the reasons for low preferred regimen use and ways to optimize preferred regimen use in HER2+ breast cancer.
Obtaining a clean catch urine sample from a baby
Authors: A Kilonback
Journal: BMJ (2017)

New quick and easy technique improves success rates

There are many situations, in primary and secondary care, when a urine sample is required as part of the safe management of an infant or child, yet the practicalities of obtaining samples can be upsetting for children and challenging for both carers and practitioners. In the linked paper (doi:10.1136/bmj.j1341), Kaufman and colleagues have developed and assessed a “Quick-Wee” method that may improve the success rate of obtaining a clean catch urine sample from a baby, in a timely manner that is likely to be highly acceptable to parents and practitioners.1

Urinary tract infection is common in children and babies and can lead to sepsis, renal scarring, and chronic kidney disease. Early identification and appropriate treatment is therefore crucial. However, the presentation is usually non-specific in a pre-continent and preverbal child and includes poor feeding, lethargy, …