tbuckley/cabot-search huggingface dataset:
Abstract 3447: Prevalence of PAD Varies Significantly Depending on the Method of Calculating Ankle Brachial Index: Results from the National Health and Nutrition Examination Survey (1999–2004)
Authors: James Reed, Sherrine Eid, Allison Parks, Bree Edris, Andrew D Sumner
Journal: Circulation (2007)

Background: Peripheral artery disease (PAD), a marker of subclinical coronary artery disease, is associated with increased morbidity and mortality. PAD is diagnosed by calculating the ankle brachial index (ABI). There exist different methods of calculating the ABI. The effects of various methods of calculating ABI on PAD prevalence is unknown. Methods: We analyzed data from three National Health and Nutrition Examination Surveys (NHANES) between the years 1999 –2004. The prevalence of PAD using three different methods of calculating ABI was determined in 5,376 participants, age 40 years and older with no prior history of cardiovascular disease . ABI, defined as an ankle-brachial index &lt;0.9, was determined using the NHANES method, HAP method, and LAP method (TABLE 1 ). Statistical analysis was performed using SPSS V15.0. Results: The prevalence of PAD among asymptomatic adults without CVD increased significantly during the six year time period 1999 –2004 regardless of the method used to determine ABI (TABLE 1 ). Across the 3 NHANES assessments, the ABI method used significantly affected calculated PAD prevalence (TABLE 1 ). The resulting differences in calculated PAD prevalence corresponds to approximately 2.2 million persons who would be reclassified as having or not having PAD based on type of ABI method. Conclusions: This study demonstrates that the calculated prevalence of asymptomatic PAD in a nationally representative sample of the United States population varies significantly by the ABI method. Further study is required to determine the most accurate method of performing ABI. TABLE 1: NHANES Method: ABI of right or left side =mean SBP (mm Hg) of the right or left ankle/ mean of the two brachial SBP (mm Hg). HAP Method: ABI of right or left side =higher of the right or left ankle SBP (mm Hg)/ higher of the two brachial SBP (mmHg). LAP Method: ABI of right or left side =lower of the right or left ankle SBP (mm Hg)/ higher of the two brachial SBP (mm Hg).
In-field and abscopal response after short-course radiation therapy in patients with metastatic Merkel cell carcinoma progressing on PD-1 checkpoint blockade: a case series
Authors: Melody J. Xu, Susan Wu, Adil I. Daud, Siegrid S. Yu, Sue S. Yom
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Patients with metastatic Merkel cell carcinoma (mMCC) who experience disease progression on immunotherapy have limited additional standard options. Given evidence of synergism between radiation therapy (RT) and immunotherapy, two patients progressing on PD-1 inhibition were referred for short-course RT. <h3>Case presentation</h3> Two patients were found to have progressive mMCC on PD-1 inhibitor therapy and were treated with single-fraction palliative RT. Both patients were observed to have local control at irradiated regions, as well as durable abscopal response at unirradiated, out-of-field, sites of metastatic disease. <h3>Conclusions</h3> Short-course RT is a compelling strategy that could be a means to augment response in patients with mMCC who show progression on immune checkpoint blockade. Ongoing clinical trials are investigating the relationship between RT and immunotherapy in mMCC.
A phase II multicenter study of the chimeric monoclonal antibody NEO102 (N) in adults with refractory colorectal cancer (CC).
Authors: Muhammad Shaalan Beg, Michael Morse, Benjamin R. Tan, Richard D. Kim, Elizabeth Poplin, Nilofer Saba Azad, Sharon Mavroukakis, Melony A. Beatson, Philip M. Arlen
Journal: Journal of Clinical Oncology (2015)

e14013 Background: NEO-102 (N) is a novel chimeric monoclonal antibody that recognizes a variant form of MUC5AC expressed by colorectal and pancreatic tumors with minimal expression on normal tissue. Its mechanism of action is through ADCC. A recent Phase III study showed patients with metastatic CC who have progressed after standard therapies had an increase in overall survival (OS) from 5 months to 6.4 months. This is a Phase II study of NEO-102 in patients with CC refractory to at least two lines of therapy. Methods: This is a phase II open label, multi-center clinical trial with N in patients with advanced CC refractory to standard therapy. An immunohistochemistry (IHC) based companion diagnostic assay is used to select eligible patients whose tumors express the target. N is administered IV every 2 weeks at the recommended phase II dose of 3.0 mg/kg with restaging every 8 weeks and retreatment in the absence of unacceptable toxicity or progressive disease (PD). A sample size of 43 patients is needed to determine an improvement in OS by at least 40% (from 5 to 7.0 months) using a one-sided significance level of 10% and 80% power. Secondary objectives include clinical efficacy by RECIST v1.1 and assessment of select immune responses including ADCC and immune cytokine profiling (Milliplex MAP Human Cytokine/Chemokine Panel). Results: Of 140 patients with CC who had archived FFPE tumor tissues tested for NPC-1 expression 60% (84/140) have stained positive (20% of cells at ≥ 2+ intensity). At this time 34 CC patients have received N at 3.0 mg/kg and are evaluable for toxicity and efficacy. N at 3.0 mg/kg is well tolerated. Median OS is 10.2 months on existing patients. Toxicities at least possibly related include grade 3 fatigue (1%), anemia (1%), hypoxia (1%), and grade 1 nausea (1%), fatigue, rash (1%), infusion reaction (1%), weight loss (1%) and constipation (1%). Conclusions: Compared to historical controls, the median overall survival of CC patients treated with NEO102 is encouraging with a favorable safety profile. Additional studies are undergoing evaluating NEO102 monotherapy and in combination with chemotherapy in pancreatic and colon cancer. Clinical trial information: NCT01040000.
Laila M F Mekawi
Authors: Hisham Abdel Rahman, Madiha Elsawi
Journal: BMJ (2018)

As a medical student, Laila M F Mekawi combined a joyous approach to life and friendships with a natural affinity for medicine built on her extraordinary empathy for patients. Her father, Fakhry Mekawi, was a pioneer in establishing medical services in Saudi Arabia. This experience had a profound impact on Laila’s …
Effect of physical activity (PA) before and after diagnosis on overall survival (OS) for patients (pts) with lymphoma.
Authors: Andrew Ip, Priyanka Avinash Pophali, Melissa C. Larson, Allison Claire Rosenthal, Matthew John Maurer, Brian K. Link, Umar Farooq, Andew L. Feldman, Cristine Allmer, Susan L. Slager, Thomas Matthew Habermann, Christopher Flowers, James Robert Cerhan, Jonathon Brett Cohen, Carrie A. Thompson
Journal: Journal of Clinical Oncology (2018)

95 Background: While PA is known to improve quality of life in lymphoma pts, its impact on OS is not known. We studied the effect of PA on OS in lymphoma pts enrolled at diagnosis in the Iowa/Mayo Molecular Epidemiology Resource. Methods: Godin Leisure Score Index (LSI; Range 0-50) was calculated based on level of PA pre-diagnosis (baseline) and 3 years post diagnosis (FU3), with pts grouped by tertile into high, moderate, or low PA. At FU3, pts also reported perceived change in PA since diagnosis. OS was measured as time from assessment (baseline or FU3) until death from any cause. Associations between LSI tertiles and OS were assessed using Cox models adjusted for lymphoma subtype, age and sex. Results: PA level was available for 3060 pts at baseline and 1371 pts at FU3. 95% had an ECOG performance status &lt; 2, 37% had an aggressive subtype, 29% had BMI ≥ 30, and 54% were age &gt; 60. Indolent lymphoma pts with higher PA at baseline had no difference in OS. Higher PA at FU3 had improved OS (moderate vs low HR 0.63, CI 0.42-0.93; high vs low HR 0.53, CI 0.33-0.86). Pts with BMI &lt; 30 who had higher PA at baseline showed no difference in OS. Higher PA at FU3 had improved OS for pts with BMI &lt; 30 (moderate vs low HR 0.68 CI, 0.48-0.98; high vs low HR = 0.41, CI 0.26-0.64). For pts &gt; 60 years, high vs low baseline PA showed improved OS (HR 0.77, CI 0.63-0.93). Higher PA at FU3 (moderate vs low HR 0.68 CI 0.48-0.96, high vs low HR 0.53 CI 0.34-0.83) was associated with OS. At FU3, compared to no change, perceived reduction of PA was associated with worse OS for indolent lymphoma (HR 2.13, CI 1.56-2.91), BMI &lt; 30 (HR 1.95, CI 1.45-2.62), BMI &gt; 30 (HR 2.00, CI 1.21-3.30), age ≤ 60 (HR 3.06, CI 1.72-5.46), and age &gt; 60 (HR 1.98, CI 1.52-2.58). Perceived increase in PA was not associated with OS. Higher PA in pts with aggressive lymphoma, BMI ≥30, and age &lt; 60 was not significantly associated with OS but trended similarly. All results were similar when analyzing by continuous LSI score. Conclusions: Higher levels of PA, especially at FU3, were associated with superior OS. The effect was more pronounced in pts with indolent lymphoma, BMI &lt; 30, or age &gt; 60. Perceived reduction in PA was associated with worse outcomes. PA should be incorporated into lymphoma survivorship plans.
Review of £10 000 gender pay gap in medicine is launched
Authors: Abi Rimmer
Journal: BMJ (2018)

The government has launched an independent review of the gender pay gap in medicine, to be led by Jane Dacre, president of the Royal College of Physicians.

The launch comes after health and social care secretary Jeremy Hunt announced in 2016 that the government would commission an independent review on how the gender pay gap could be eliminated in medicine.1

On announcing the review on 28 May, the department of health and social care said that male doctors were paid an average of £67 788 in basic pay, compared with £57 569 for …
Biomimetic O2-Evolving metal-organic framework nanoplatform for highly efficient photodynamic therapy against hypoxic tumor
Authors: Shutao Gao, Pengli Zheng, Zhenhua Li, Xiaochen Feng, Weixiao Yan, Shizhu Chen, Weisheng Guo, Dandan Liu, Xinjian Yang, Shuxiang Wang, Xing-Jie Liang, Jinchao Zhang
Journal: Biomaterials (2018)
Female breast cancer in Central Sudan - A tragedy of young age and late presentation
Authors: Dafalla Abuidris, Elgaili Elgaili, Munazzah Rahman, Sulma Mohammed
Journal: Cancer Research (2008)

3851   Statistics on the clinical profile of breast cancer in Sudan are lacking for want of a population-based cancer registry, socioeconomic and demographic infrastructure, and awareness by women.   The  purpose  of this study was to investigate the clinical presentation and outcome of Sudanese women with breast cancer and determine breast cancer tissue estrogen and progesterone receptors status. Data from 1255 patients, registered and treated at the Faculty of Medicine and Institute of Nuclear Medicine, Molecular Biology, and Oncology (INMO), University of Gezira from January 1999 to December 2006, were analyzed for age, histologic type of breast cancer, site and size of the tumor, and stage at presentation. In stark contrast to the situation in other countries, premenopausal women (age  10.0 cm. Tumors tended to occur predominantly on the left (50%) upper lateral quadrant (54.75%). Tumors were staged as 0 (0.48%), I (11.31%), IIA (8.21%), IIB (19.28%), IIIA (18.09%), IIIB (18.01%), and IV (24.62%). We conclude that breast cancer patients in Sudan tend to be younger than those in other countries, but present with a higher histologic grade and later stage at the time of diagnosis.
Dissecting primary resistance to anti-EGFRs in RAS and BRAF wt metastatic colorectal cancer (mCRC): A case-control study.
Authors: Chiara Cremolini, Federica Morano, Roberto Moretto, Rosa Berenato, Elena Tamborini, Federica Perrone, Daniele Rossini, Annunziata Gloghini, Adele Busico, Gemma Zucchelli, Chiara Baratelli, Emiliano Tamburini, Iolanda Capone, Chiara Volpi, Massimo Milione, Massimo Di Maio, Gabriella Fontanini, Filippo G. De Braud, Alfredo Falcone, Filippo Pietrantonio
Journal: Journal of Clinical Oncology (2017)

11508 Background: Almost half of RAS and BRAFwt mCRC patients do not respond to anti-EGFRs. Different molecular alterations suggested as predictors of resistance have not been validated. Methods: We conducted a case-control study to prospectively demonstrate the negative predictive impact of HER-2 amplification or mutations (mut), MET amplification, NTRK/ROS1/ALK/RET rearrangements, and mut activating MAPKs or PI3K/Akt axis. Patients with RAS and BRAFwt mCRC clearly resistant (cases) or clearly sensitive (controls) to anti-EGFRs were selected. Hypothesizing a prevalence of candidate alterations of 0% and 15% among controls and cases, 47 cases and 47 controls were needed to be able to reject the null hypothesis of equally prevalent alterations, with a- and b- error 0.05 and 0.20. Since hypermutated tumors may hardly rely on a single pathway for their growth, we also evaluated the impact of microsatellite instability. Results: 47 cases and 47 controls were included. Primary endpoint was met: mentioned alterations were reported in 20 (42.6%) cases and 1 (2.1%) control (p&lt;0.001). MSI-high was significantly more frequent among resistant than sensitive tumos (15% vs 0%, p&lt;0.001). Conclusions: This is the first prospective demonstration that the combined assessment of these rare alterations allows to better select patients for anti-EGFRs, while opening the way to other tailored therapies. [Table: see text]
SAFE-HEaRt: A pilot study assessing the cardiac safety of HER2 targeted therapy in patients with HER2 positive breast cancer and reduced left ventricular function.
Authors: Filipa Lynce, Ana Barac, Xue Geng, Chau T. Dang, Anthony Francis Yu, Karen L. Smith, Christopher Gallagher, Paula Raffin Pohlmann, Raquel Nunes, Pia Maarit Herbolsheimer, Robert D. Warren, M. Barbara Srichai, Mark Hofmeyer, Andrecia Cunningham, Patricia Timothee, Federico M Asch, Ayesha N Shajahan-Haq, Ming Tony Tan, Claudine Isaacs, Sandra M. Swain
Journal: Journal of Clinical Oncology (2018)

1038 Background: HER2 targeted therapies have substantially improved the prognosis of patients with BC however they can be associated with cardiac toxicity. SAFE-HEaRt is the first investigator-initiated trial that prospectively tests whether HER2 therapies may be safely administered in patients with reduced LV function in the setting of ongoing cardiac treatment and monitoring. Methods: Eligibility criteria: stage I-IV HER2 positive BC candidates for non-lapatinib therapy; LV ejection fraction (LVEF) ≥40% and < 50% and no symptoms of heart failure (HF). All patients had cardiology visits and echocardiograms at baseline, during treatment and 6 months after treatment, and received beta blockers (BB) and ACE inhibitors (ACEi) unless contraindicated. Primary endpoint was completion of planned oncologic HER2 therapy without development of a cardiac event (CE), defined as HF symptoms or asymptomatic decline in LVEF ≥10% points from baseline and/or to LVEF ≤35%. Results: Of 31 enrolled patients, 30 were evaluable. Mean age was 54 years, 18 had early stage and 13 metastatic disease. Seventeen patients had prior exposure to anthracyclines and 13 had hypertension. On study 15 patients were treated with trastuzumab, 14 trastuzumab/pertuzumab and 2 ado-trastuzumab emtansine. Mean LVEF was 45% at baseline and 46% at the end of treatment. Twenty-two patients completed HER2 therapy as defined per protocol without development of a CE and 5 are still on study. Three patients met CE criteria: 2 developed symptomatic HF (at 24 and 36 wks) and 1 had protocol defined LVEF decline to 35% at 12 wks, all were taken off study. Two of these 3 patients are alive and in follow up and 1 died of disease progression. Demographics, previous anthracyclines and baseline LVEF did not predict development of CEs. Elevation of highly sensitive troponin preceded 2 of 3 CEs which was significant (p = 0.003). Conclusions: Patients with BC and mildly reduced LVEF can safely receive HER2 therapies in the setting of regular cardiac monitoring and treatment with BB and ACEi. Our results provide new safety data in this unique population and have potential to contribute to clinical practice changes. Clinical trial information: NCT01904903.
Protective paraspeckle hyper-assembly downstream of TDP-43 loss of function in amyotrophic lateral sclerosis
Authors: Tatyana A. Shelkovnikova, Michail S. Kukharsky, Haiyan An, Pasquale Dimasi, Svetlana Alexeeva, Osman Shabir, Paul R. Heath, Vladimir L. Buchman
Journal: Molecular Neurodegeneration (2018)

Paraspeckles are subnuclear bodies assembled on a long non-coding RNA (lncRNA) NEAT1. Their enhanced formation in spinal neurons of sporadic amyotrophic lateral sclerosis (ALS) patients has been reported but underlying mechanisms are unknown. The majority of ALS cases are characterized by TDP-43 proteinopathy. In current study we aimed to establish whether and how TDP-43 pathology may augment paraspeckle assembly. Paraspeckle formation in human samples was analysed by RNA-FISH and laser capture microdissection followed by qRT-PCR. Mechanistic studies were performed in stable cell lines, mouse primary neurons and human embryonic stem cell-derived neurons. Loss and gain of function for TDP-43 and other microRNA pathway factors were modelled by siRNA-mediated knockdown and protein overexpression. We show that de novo paraspeckle assembly in spinal neurons and glial cells is a hallmark of both sporadic and familial ALS with TDP-43 pathology. Mechanistically, loss of TDP-43 but not its cytoplasmic accumulation or aggregation augments paraspeckle assembly in cultured cells. TDP-43 is a component of the microRNA machinery, and recently, paraspeckles have been shown to regulate pri-miRNA processing. Consistently, downregulation of core protein components of the miRNA pathway also promotes paraspeckle assembly. In addition, depletion of these proteins or TDP-43 results in accumulation of endogenous dsRNA and activation of type I interferon response which also stimulates paraspeckle formation. We demonstrate that human or mouse neurons in vitro lack paraspeckles, but a synthetic dsRNA is able to trigger their de novo formation. Finally, paraspeckles are protective in cells with compromised microRNA/dsRNA metabolism, and their assembly can be promoted by a small-molecule microRNA enhancer. Our study establishes possible mechanisms behind paraspeckle hyper-assembly in ALS and suggests their utility as therapeutic targets in ALS and other diseases with abnormal metabolism of microRNA and dsRNA.
A phase II, single arm study assessing the efficacy of pembrolizumab (Pembro) plus radiotherapy (RT) in metastatic triple negative breast cancer (mTNBC).
Authors: Heather L. McArthur, Christopher Andrew Barker, Ayca Gucalp, Lizza Lebron-Zapata, Yong Hannah Wen, Cindy Kallman, Alessandro D'Agnolo, Micaela Rodine, Brittany Arnold, Zhigang Zhang, Alice Y. Ho
Journal: Journal of Clinical Oncology (2018)

1017 Background: Overall response rates of 5-7% have been reported with checkpoint inhibitor monotherapy in PD-L1-unselected mTNBC as second line or subsequent therapy. RT is frequently used to enhance local control in mTNBC and has been reported to induce distant (abscopal) tumor responses when combined with immunotherapy. In this study, we evaluate the safety and efficacy of RT combined with pembro, a programmed death 1 (PD-1) inhibitor, in a phase II, single-arm, Simon two-stage, study in mTNBC. Methods: Eligible women had biopsy-proven mTNBC and ≥2 measurable sites of metastatic disease with at least one site requiring RT. PD-L1 expression was not required for study entry. A total RT dose of 3000 cGy was delivered in 5 daily fractions. Pembro was given intravenously at 200 mg within 3 days of the first RT fraction, then every 3 weeks +/-3 days until disease progression. The primary endpoint was overall response rate at week 13 in the non-irradiated lesions by RECIST v1.1. Secondary endpoints included safety and overall survival. Tumor biopsies were obtained at baseline and at week 7. Results: Of the 17 women enrolled, the median age was 52 y (range 37-73y), and the median number of prior cytotoxic therapies for metastatic disease was 3 (range 0 to 8). Of the 8 women not evaluable at 13 weeks: 5 died secondary to disease-related complications (at weeks 2, 6, 7, 8, and 9) and 3 progressed prior to week 13. Of the 9 women evaluable at week 13, 3 (33%) had a partial response, 1 (11%) had stable disease and 5 (56%) had disease progression. The stable disease response was durable for 22 weeks. The 3 partial responses represented 60%, 54%, and 34% decreases in tumor burden by RECIST v1.1 and were durable for 31, 21, and 40 weeks, respectively. Common toxicities were mild and included fatigue, myalgia and nausea. Conclusions: The combination of pembro and RT was well-tolerated with durable responses outside the RT field in 3/9 (33%) evaluable patients unselected for PD-L1 expression. Thus, the addition of RT to PD-1 blockade represents a promising strategy for improving response rates in pre-treated mTNBC. Clinical trial information: NCT02730130.
“We would employ Hadiza Bawa-Garba,” say 159 paediatricians
Authors: Abi Rimmer
Journal: BMJ (2018)

A group of 159 paediatricians have signed a letter in support of Hadiza Bawa-Garba, a trainee paediatrician convicted of gross negligence manslaughter.

In a letter published in The BMJ the doctors say that they “are confident to employ Bawa-Garba with supervision in a training position upon her reinstatement to the medical register and pending her employment in a substantive post that will facilitate her return to work when she is reinstated.”1

In 2015 Bawa-Garba was convicted of manslaughter after the death …
Family medicine providers' perceptions of their ability to provide evidence-based survivorship care.
Authors: Maria Alma Rodriguez, Guadalupe R. Palos, Katherine Ramsey Gilmore, Paula A. Lewis-Patterson, Lewis E. Foxhall, Laura Aubree Shay
Journal: Journal of Clinical Oncology (2018)

16 Background: Opportunities for medical students and primary care providers to learn about evidence-based cancer survivorship care remains limited. To fill this void, we created an innovative curriculum using ECHO, a tele-mentoring approach, to teach faculty and residents in family medicine programs about the core principles and skills of survivorship care. Our objective was to explore participants' perceptions about their self-efficacy to deliver high quality care to survivors. Methods: Subjects were recruited from 3 academic centers with medical residency programs collaborating with our cancer center in a state-funded education grant to develop a tele-mentoring training program. The survey, which was developed by the research team, measured self-efficacy and satisfaction. Subjects were asked to rate their confidence in their abilities to offer evidence-based care after completing the program. Descriptive statistics were used to report results. REDCap, a web-based application, was used to manage the development and distribution of the survey. Results: A total of 116 surveys were sent out electronically with 59 returned (50.9%). Table 1 indicates most participants reported the ECHO program increased their knowledge, clinical skills, and expertise to provide comprehensive survivorship care. Conclusions: Overall, the participants’ perceptions of their expertise to offer optimal survivorship care were positive. There is room for improvement to maximize the learning experience for all participants.[Table: see text]