tbuckley/cabot-search huggingface dataset:
Caution Regarding Government-Mandated Shared Decision Making for Patients With Atrial Fibrillation
Authors: Megan Coylewright, David R. Holmes
Journal: Circulation (2017)

lthough cardiovascular clinicians are increasingly encouraged to incorporate a shared decision-making (SDM) approach with their patients with atrial fibrillation (AF) at risk for stroke, limited guidance is available on how to navigate this complex interaction.Referring physicians, who know their patients best, struggle to present risks and benefits of newer therapies, whereas subspecialists are challenged to rapidly learn new patients' values and preferences.Decision aids are consistently shown to improve patient outcomes, such as knowledge, engagement, and satisfaction, 1 yet poor implementation of an SDM approach by clinicians across routine practice speaks to the ongoing need for a greater understanding of where in the care process SDM is best used and with what tools. 2 In this context, the Centers for Medicare and Medicaid Services (CMS) mandated SDM for patients with AF seeking to reduce their stroke risk.In March 2015, the US Food and Drug Administration approved Watchman (Boston Scientific), a cardiac device that occludes the left atrial appendage where most clots are formed in AF.The device was approved for patients with an appropriate rationale to select a percutaneously implanted device over anticoagulation, "taking into account the safety and effectiveness of the device." 3CMS then released a National Coverage Determination, which prescriptively outlined the healthcare delivery processes required to take place before left atrial appendage closure (LAAC).Referring physicians (nonimplanters) must document evidence of an SDM interaction regarding anticoagulation choices with an evidence-based decision aid.Much angst, confusion, and questions have resulted from this mandate (eg, are nonimplanters required to lead an SDM interaction on LAAC in detail, a procedure for which many are not yet familiar?).Per the National Coverage Determination, the answer is no.The SDM mandate is regarding the choice of oral anticoagulation (ie, referring physicians must first document an appropriate rationale [US Food and Drug Administration language] to not use an anticoagulant).The implications of mandating that SDM take place upstream means it is possible the initial interactions may not include information on all choices appropriate for the patient or that the patient may require a second visit with their referring clinician to fulfill the mandate.
A real-world retrospective study of apatinib plus chemotherapy in metastatic breast cancer.
Authors: Anjie Zhu, Peng Yuan, Jiayu Wang, Fei Ma, Yang Luo, Ying Fan, Qing LI, Pin Zhang, Binghe Xu
Journal: Journal of Clinical Oncology (2017)

e12507 Background: Antiangiogenic therapy in combination with chemotherapy has shown improved clinical outcome in advanced breast cancer(ABC). Apatinib is an orally administered tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2(VEGFR-2), which exhibited objective efficacy in metastatic breast cancer(MBC). We performed a retrospective observational analysis to evaluate the efficacy and safety of apatinib plus chemotherapy in the real-world practice of patients with MBC. Methods: Patients who have failed at least one prior chemotherapy regimen for metastatic disease were included in this study. The primary endpoint was progression free survival(PFS). Secondary end points included objective response rate(ORR), clinical benefit rate(CBR), overall survival(OS) and safety. Data analysis included association between clinicopathological characteristics or treatment choice and PFS. Results: Of the 23 patients analyzed, 14(60.9%) received plant-derived anticancer agents combined therapy and 9(39.1%) combined with non-plant-derived agents. Objective response rate(ORR) was 34.7% and clinical benefit rate(CBR) reached 52.2% on last tumor assessment. With a median follow-up of 9.0 months, the estimated median PFS and OS were 5.4 months (95%CI 3.5-7.3) and 8.2 months (95%CI 4.7-11.7), respectively. Toxicities were tolerable or could be clinically managed.The most frequently observed adverse events (AEs) of all grade were hypertension, myelosuppression, hand-foot syndrome, proteinuria, fatigue and gastrointestinal reaction. The most common grade 3/4 treatment-related AEs were myelosuppression(39.1%) and gastrointestinal reaction(17.4%). Conclusions: In this retrospective observational study, combination of apatinib with chemotherapy demonstrated clinically relevant efficacy and tolerability in metastatic breast cancer.
Long-term survival in advanced-stage uterine papillary serous carcinoma.
Authors: Laura L. Holman, David A. Iglesias, Pamela T. Soliman, Navdeep Pal, Ann Klopp, Russell Broaddus, Tina Ayeni, Nicole Dierschke Fleming, Mark F. Munsell, Karen H. Lu, Shannon Neville Westin
Journal: Journal of Clinical Oncology (2013)

5596 Background: Advanced-stage (III/IV) uterine papillary serous carcinoma (UPSC) has a median overall survival (OS) of ~ 3 yrs. The study objective was to determine factors associated with long-term survival in advanced stage UPSC. Methods: We performed a retrospective review of pts diagnosed with stage III or IV UPSC between 1993 and 2012. Summary statistics were used to describe demographic and clinical characteristics. OS was estimated with the Kaplan-Meier estimator. Fisher’s exact test and the Wilcoxon rank sum test were used to compare pts surviving &gt;3 yrs with those surviving &lt;1 yr. Results: With a median follow-up of 2.2 years (range 0.06-13.2), 262 pts with advanced stage UPSC were identified. The probability of surviving &gt;3 yrs was 0.462, &gt;4 yrs was 0.310, and &gt;5 yrs was 0.228. Thirty-six (14%) pts survived &gt;3 yrs and 37 (14%) survived &lt;1 yr. There was no difference in median age of pts surviving &gt;3 yrs compared to pts surviving &lt;1 yr (60 vs 66, p=0.21). There was also no difference between groups in demographics or medical history. There were several significant differences in pathologic and treatment variables between groups (Table). Conclusions: Though rare, long-term survival in advanced stage UPSC is associated with mixed histology, combination treatment including chemotherapy, and complete response to primary therapy. Further study of the molecular basis for these differences has the potential to improve survival for all pts with this disease. [Table: see text]
<i>JAK2</i> V617F Mutation Testing in Patients Presenting With Hepatic and Portal Vein Thrombosis
Authors: Charles Elliott Foucar, Brady Lee Stein
Journal: JAMA (2017)

A 27-year-old woman with pain in the right upper quadrant underwent a laparoscopic cholecystectomy. Lab tests were positive for JAK2 V617F, confirming the presence of clonal hematopoiesis. How would you proceed?
The Need to Test Strategies Based on Common Sense
Authors: Elaine C. Khoong, Joseph S. Ross
Journal: JAMA Internal Medicine (2017)

Laura A. Young, MD, PhD; John B. Buse, MD, PhD; Mark A. Weaver, PhD; Maihan B. Vu, DrPH, MPH; C. Madeline Mitchell, MURP; Tamara Blakeney, BS; Kimberlea Grimm, BAS; Jennifer Rees, RN, CPF; Franklin Niblock, BS; Katrina E. Donahue, MD, MPH; for the Monitor Trial Group
Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies
Authors: Xue Li, Xiangrui Meng, Maria Timofeeva, Ioanna Tzoulaki, Konstantinos K Tsilidis, P A Ioannidis, Harry Campbell, Evropi Theodoratou
Journal: BMJ (2017)

<b>Objective</b> To map the diverse health outcomes associated with serum uric acid (SUA) levels. <b>Design</b> Umbrella review. <b>Data sources</b> Medline, Embase, Cochrane Database of Systematic Reviews, and screening of citations and references. <b>Eligibility criteria</b> Systematic reviews and meta-analyses of observational studies that examined associations between SUA level and health outcomes, meta-analyses of randomised controlled trials that investigated health outcomes related to SUA lowering treatment, and Mendelian randomisation studies that explored the causal associations of SUA level with health outcomes. <b>Results</b> 57 articles reporting 15 systematic reviews and144 meta-analyses of observational studies (76 unique outcomes), 8 articles reporting 31 meta-analyses of randomised controlled trials (20 unique outcomes), and 36 articles reporting 107 Mendelian randomisation studies (56 unique outcomes) met the eligibility criteria. Across all three study types, 136 unique health outcomes were reported. 16 unique outcomes in meta-analyses of observational studies had P&lt;10<sup>-6</sup>, 8 unique outcomes in meta-analyses of randomised controlled trials had P&lt;0.001, and 4 unique outcomes in Mendelian randomisation studies had P&lt;0.01. Large between study heterogeneity was common (80% and 45% in meta-analyses of observational studies and of randomised controlled trials, respectively). 42 (55%) meta-analyses of observational studies and 7 (35%) meta-analyses of randomised controlled trials showed evidence of small study effects or excess significance bias. No associations from meta-analyses of observational studies were classified as convincing; five associations were classified as highly suggestive (increased risk of heart failure, hypertension, impaired fasting glucose or diabetes, chronic kidney disease, coronary heart disease mortality with high SUA levels). Only one outcome from randomised controlled trials (decreased risk of nephrolithiasis recurrence with SUA lowering treatment) had P&lt;0.001, a 95% prediction interval excluding the null, and no large heterogeneity or bias. Only one outcome from Mendelian randomisation studies (increased risk of gout with high SUA levels) presented convincing evidence. Hypertension and chronic kidney disease showed concordant evidence in meta-analyses of observational studies, and in some (but not all) meta-analyses of randomised controlled trials with respective intermediate or surrogate outcomes, but they were not statistically significant in Mendelian randomisation studies. <b>Conclusion</b> Despite a few hundred systematic reviews, meta-analyses, and Mendelian randomisation studies exploring 136 unique health outcomes, convincing evidence of a clear role of SUA level only exists for gout and nephrolithiasis.
Personalized therapy for metastatic colorectal cancer in Colombia (ONCOLGroup).
Authors: Carlos A. Vargas, Hernan Carranza, Jorge M. Otero, Henry A. Becerra, Andres Acevedo, July Rodriguez, Pilar Archila, Orlando Ricaurte, Rafael Garcia, Eduardo Londono, Jorge Padron, Carlos Martinez, Javier Romero, Javier Romero, Andres F. Cardona
Journal: Journal of Clinical Oncology (2014)

e14635 Background: Targeted therapies have improved the survival of patients with metastatic colorectal cancer (mCRC). Data about expression of EGFR, KRAS, NRAS, and BRAF mutation status, and PI3K/PTEN expression improved patient selection for targeted treatments. Methods: This study included 202 patients with mCRC who were treated at the Fundación Santa Fe de Bogotá (FSFB) from March 2009 to March 2013. The overall response rate (ORR), clinical benefit (CB), progression free survival (PFS) and overall survival (OS) were estimated. The OS was analysed according to KRAS, BRAF and PI3K mutational profile. Results: Median age was 58,5-yo (+/- 9.7); 88% on included pts had ECOG 0-1 and dominant metastatic sites were the liver (53.5%), regional lymph nodes (15.3%), lungs (9.4%) and the peritoneum (9.9%). All patients received first line chemotherapy plus some monoclonal antibody (78% involving bevacizumab). ORR was 32.3% and CB reached 76% in the 152 evaluable patients. First line PFS was 7.6-mo (95%CI 4.9-9.2), higher for combinations including bevacizumab compared to cetuximab (7.9 vs. 4.5-mo; p=0.012). The median time for the maintenance following first line treatment (PS1) was 5.9-mo (95%C 3.2-14.2). Median OS was 36 months (95%CI 29.7-42.9), time extended in patients treated with some monoclonal antibody compared to those only receiving conventional chemotherapy (30.5 vs. 25 months; p=0.007) and in KRAS-Wt population (40 vs. 26-mo for KRAS mutants; p=0.028). OS was also higher amongst those receiving second (27.7 months vs. 10.3-mo; p=0.0001) and third line interventions (23 vs.9.7-mo; p=0.06). 32.7% of the tumours harboured a KRAS mutation, 10.9% harboured a PIK3CA mutation, and 6.4% harboured a BRAF mutation. OS for BRAF-Wt population was 30-mo (95%CI 20.1-41.0), whilst those carrying the BRAF mutation lived for 13-mo (95%CI 9.2-17.0; p=0.09). Conclusions: These results agreed with those previously described in the literature. Routine genotyping and its correlation with diverse outcomes in mCRC in Colombia are possible and necessary to improved patient selection for targeted treatments.
Detection of circulating tumor cells with epithelial-mesenchymal transition phenotype as critical surrogate biomarkers in patients with non-small cell lung cancer.
Authors: Shinsaku Togo, Kazuya Takamochi, Shiaki Oh, Masaaki Ouchi, Nobuyoshi Katagiri, Yasuo Urata, Fuminori Sakurai, Hiroyuki Mizuguchi, Kenji Suzuki, Kazuhisa Takahashi
Journal: Journal of Clinical Oncology (2014)

e22031 Background: Circulating tumor cells (CTC) have a crucial role in clinical outcome of patients. However, low counts of CTCs have been reported in patient with non-small cell lung cancer (NSCLC) by methods using EpCAM antigen expression. The loss of epithelial markers could therefore lead to an underestimation of CTCs with mesenchymal phenotype. Epithelial-mesenchymal transition (EMT) is considered as an essential process in the metastatic cascade and acquiring chemoresistance. The aim of this study is to investigate CTCs with mesenchymal phenotype as surrogate biomarkers by using the new telomerase-specific replication-selective adenovirus TelomeScan F35 (OBP-1101). Methods: Peripheral venous blood samples were obtained from 26 patients with resected NSCLC and 8 patients with advanced NSCLC before and after 1W of first-line chemotherapy. The viable human CTCs were visualized as GFP positive to count the CTCs by OBP-1101. Then triply labelled with fluorescent anti-vimentin, anti-EpCAM and anti-CD45 antibodies in immunocytochemical analysis. Results: The sensitivity of CTCs in stage I, II, III and IV patients were 32, 50, 40 and 75% respectively (1-3 cells/7.5ml). None of healthy volunteers could not detect CTC (specificity: 100% n= 38). CTCs expressing vimentin were detected in 12/33 (EMT-CTC: 36.4%) patients, but were less frequent only EpCAM positive CTCs (non -EMT-CTC: 12%). The sensitivity of EMT-CTC in stage IA adenocarcinoma was 46.2% and higher than that of the existing clinical biomarkers such as CEA and SLX (CEA: 0.17% and SLX: 0.17%). The group of patients with positive EMT-CTC at baseline presented poor clinical outcome of first-line chemotherapy (4/4: no responder) than those with negative EMT-CTC at baseline (3/4: responder). The patients detected EMT-CTC after 1W did not response to chemotherapy and all of non-EMT-CTCs were disappeared after 1W of chemotherapy. Conclusions: OBP-1101 could achieve high sensitivity to detect the viable CTC even in patients with early-stage NSCLC. The CTCs with mesenchymal phenotype are crucial surrogate indicator of chemotherapeutic efficacy in NSCLC patients.
Author’s reply to Spitzer
Authors: Shyam Verma
Journal: BMJ (2017)

I thank Spitzer for his comments on steroid modified tinea.12 All interested general practitioners treating dermatophytosis should read Schaller and colleagues’ comprehensive review of a recent expert panel meeting on topical treatment of superficial mycoses.3

The authors recommend the use of topical corticosteroids and antifungal combination creams with several important …
Impact of Oncotype-DX testing on choice of chemotherapy.
Authors: Walter Yip, Krzysztof Dobosz, Caroline Illmann, Kaylie Willemsma, Christine E. Simmons
Journal: Journal of Clinical Oncology (2017)

e12049 Background: The Oncotype DX test has been shown to change treatment plans in ~30% of cases, but it is unclear if it changes the type of chemotherapy offered. We sought to determine if the availability of Oncotype DX testing in BC resulted in a change in the type of chemotherapy regimens used on early stage breast cancer pts. Methods: This was a cohort study in which pts treated in the 2 years prior to the availability of Oncotype Dx testing were compared to pts treated in the 2 years after it became available in BC. Charts were audited and divided into pre- and post- availability of Oncotype DX testing. The groups were compared for differences in length of chemotherapy (12 vs &gt; 12 weeks), type of agents used (anthracycline vs non-anthracycline) and myelosuppressive potential of regimen chosen. Results: A total of 831 pts fulfilled enrollment criteria; 360 were seen in the pre Oncotype era and 471 were seen in the post Oncotype era. A total of 250 (30.1%) pts were treated with chemotherapy in both cohorts with a median age of 59 for both groups (range of 29-80 and 24-80 respectively, p = NS). There was a decrease of 11.5% in pts receiving chemotherapy from 36.6% to 25.1% (p = 0.0003). Of the pts who received chemotherapy, there was a shift away from regimens containing anthracycline (49.2% vs 32.2%, p = 0.0070) and a shift towards more myelosuppressive chemotherapy regimens (p = 0.0344). There was a significant difference in the duration of chemotherapy regimens chosen with post Oncotype era pts receiving short course chemotherapy 69.5% of the time, compared to only 56.8% in the pre Oncotype era (p = 0.0491). Conclusions: The availability of Oncotype DX testing has resulted in a shift towards use of shorter, more myelosuppressive, non-anthracycline containing chemotherapy protocols. Since being publicly available, fewer pts are receiving chemotherapy but our data suggests a 10% change in treatment plan compared to the 30% change seen in other literature. Further study is warranted to ensure long term outcomes are not negatively impacted by the move towards shorter chemotherapy regimens.
Cancer Therapy: Injectable Supramolecular Hydrogels as Delivery Agents of Bcl‐2 Conversion Gene for the Effective Shrinkage of Therapeutic Resistance Tumors (Adv. Healthcare Mater. 11/2017)
Authors: Xuan Liu, Xiaohong Chen, Ming Xuan Chua, Zibiao Li, Xian Jun Loh, Yun‐Long Wu
Journal: Advanced Healthcare Materials (2017)

In article number 1700159, Zibiao Li, Xian Jun Loh, Yun-Long Wu, and co-workers design injectable MPEG-PCL-PEI/α-CD based supramolecular hydrogels that possess good sustained release ability of Bcl-2 conversion genes in form of polyplex, to effectively inhibit in vivo tumor growth. This long term "enemy to friend" strategy will benefit various applications, including on-demand gene delivery and personalized medicine.
Comparative effectiveness of allopurinol versus febuxostat for preventing incident renal disease in older adults: an analysis of Medicare claims data
Authors: Jasvinder A Singh, John D Cleveland
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objective</h3> To assess the comparative effectiveness of allopurinol versus febuxostat for preventing incident renal disease in elderly. <h3>Methods</h3> In a retrospective cohort study using 2006–2012 Medicare claims data, we included patients newly treated with allopurinol or febuxostat (baseline period of 183 days without either medication). We used 5:1 propensity-matched Cox regression analyses to compare the HR of incident renal disease with allopurinol use (and dose) versus febuxostat (reference). Sensitivity analyses included multivariable-adjusted regression models. <h3>Results</h3> There were 31 465 new allopurinol or febuxostat treatment episodes in 26 443 patients; 8570 ended in incident renal disease. Crude rates of incident renal disease per 1000 person-years were 192 with allopurinol versus 338 with febuxostat. Crude rates of incident renal disease per 1000 person-years were lower with higher daily dose: allopurinol &lt;200, 200–299 and ≥300 mg/day with 238, 176 and 155; and febuxostat 40 and 80 mg/day with 341 and 326, respectively. In propensity-matched analyses, compared with febuxostat, allopurinol use was associated with lower HR of incident renal disease, 0.61 (95% CI 0.49 to 0.77). Compared with febuxostat 40 mg/day, allopurinol doses &lt;200, 200–299 and ≥300 mg/day were associated with lower HR of incident renal disease, 0.75 (95% CI 0.65 to 0.86), 0.61 (95% CI 0.52 to 0.73) and 0.48 (95% CI 0.41 to 0.55), respectively. Sensitivity analyses using multivariable-adjusted regression confirmed these findings. <h3>Conclusions</h3> Allopurinol was associated with a lower risk of incident renal disease in elderly patients than febuxostat. Future studies need to examine the mechanism of this potential renal benefit of allopurinol.
Targeted Delivery to Tumor-associated Pericytes via an Affibody with High Affinity for PDGFRβ Enhances the <i>in vivo</i> Antitumor Effects of Human TRAIL
Authors: Ze Tao, Hao Yang, Qiuxiao Shi, Qing Fan, Lin Wan, Xiaofeng Lu
Journal: Theranostics (2017)

Human tumor necrosis factor-related apoptosis-inducing ligand (hTRAIL) has exhibited superior in vitro cytotoxicity in a variety of tumor cells.However, hTRAIL showed a disappointing anticancer effect in clinical trials, although hTRAIL-based regimens were well tolerated.One important reason might be that hTRAIL was largely trapped by its decoy receptors, which are ubiquitously expressed on normal cells.Tumor-targeted delivery might improve the tumor uptake and thus enhance the antitumor effect of hTRAIL.Platelet-derived growth factor receptor β (PDGFRβ)-expressing pericytes are enriched in tumor tissues derived both from patients with colon cancer and from mice bearing colorectal tumor xenografts.A ZPDGFRβ affibody showed high affinity (nM) for PDGFRβ and was predominantly distributed on tumor-associated PDGFRβ-positive pericytes.Co-administration with the ZPDGFRβ affibody did not significantly enhance the antitumor effect of hTRAIL in mice bearing tumor xenografts.Fusion to the ZPDGFRβ affibody endows hTRAIL with PDGFRβ-binding ability but does not interfere with its death receptor binding and activation.The fused ZPDGFRβ affibody mediated PDGFRβ-dependent binding of hTRAIL to pericytes.In addition, hTRAIL bound on pericytes could kill tumor cells through juxtatropic activity or exhibit cytotoxicity in tumor cells after being released from pericytes.Intravenously injected hTRAIL fused to ZPDGFRβ affibody initially accumulated on tumor-associated pericytes and then diffused to the tumor parenchyma over time.Fusion to the ZPDGFRβ affibody increased the tumor uptake of hTRAIL, thus enhancing the antitumor effect of hTRAIL in mice bearing tumor xenografts.These results demonstrate that pericyte-targeted delivery mediated by a ZPDGFRβ affibody is an alternative strategy for tumor-targeted delivery of anticancer agents.