tbuckley/cabot-search huggingface dataset:
Efficacy of omega-3 (ω3) supplementation versus omega-6 (ω6) supplementation for reducing pain among breast cancer survivors: A URCC NCORP RCT.
Authors: Luke Joseph Peppone, Julia Ellen Inglis, Karen Michelle Mustian, Kah Poh Loh, Eva Culakova, Ian Kleckner, Charles Stewart Kamen, Gilbert D. A. Padula, Supriya Gupta Mohile, Po-Ju Lin, Sharon Cole, Michelle Christine Janelsins
Journal: Journal of Clinical Oncology (2018)

10118 Background: Pain is a highly prevalent side effect of breast cancer therapy. High pain levels can reduce treatment adherence and increase discontinuation rates for hormonal therapies (HT) while reducing quality of life. We conducted a multi-site, blinded phase II RCT examining the efficacy of ω3 fatty acid (fish oil) supplementation versus ω6 fatty acid (soybean oil) supplementation for improving pain through the URCC NCORP. Methods: Breast cancer survivors between 4-36 months post-adjuvant therapy were randomized into 3 arms: 1) High-dose ω3 (ω3; 6 g/day), 2) Low-dose ω3/ω6 (ω3/ω6; ω3: 3 g/day and ω6: 3 g/day) and 3) High-dose ω6 (ω6; 6 g/day) for 6 weeks. Pain was assessed via the Brief Pain Inventory (BPI) at pre- and post-intervention. Serial blood was collected for serum fatty acid and inflammatory biomarker analysis. ANCOVAs, controlling for baseline pain and type of HT (AI, tamoxifen, or none), were used to calculate mean change from baseline to post-intervention for this secondary data analysis. Results: 108 female breast cancer survivors were accrued (93% white, mean age = 60). Biochemical blood analyses confirmed high compliance in all arms with minimal contamination. Mean baseline Worst Pain levels did not differ between groups (ω3 = 4.9, ω3/ω6 = 5.6, ω6 = 4.7; p = 0.43). The mean Worst Pain score decreased by 0.8 points for ω3, by 0.8 points for ω3/ω6, and by 1.7 points for ω6 (ω3 vs ω6 p-value = 0.18). The mean change in Current Pain score was more pronounced (Change score: ω6 = −1.8 vs ω3/ω6 = −0.8 vs ω3 = −0.5; ω3 vs ω6 p = 0.05) and indicated a dose-response. Similar changes were found for Average Pain and Least Pain but the differences were not significant. The ω6 group had a significant reduction in the inflammatory biomarker IL-6 compared to the ω3 group (IL-6 change: ω3 = +0.17 vs ω6 = −0.30; p < 0.01). Conclusions: ω6 supplementation reduced pain levels compared to ω3 supplementation in breast cancer survivors. ω6 also significantly reduced IL-6 levels compared to ω3, indicating a potential mechanism of action. Further research is needed on the effects of ω6 fatty acids in cancer patient. Funding: NCI R03CA175599 & UG1CA189961. Nordic Naturals Inc. supplied all study agents. Clinical trial information: NCT02352779.
High Prevalence of Oncogenic MYD88 and CD79B Mutations in Intravascular Large B-Cell Lymphoma: Implication for Therapy with Bruton's Kinase Inhibitors?
Authors: Sebastiaan Somers, Patty Jansen, Hendrik Veelken, Maarten Vermeer, Willem Kraan, Anne-Roos Schrader, Ward Posthuma, Marcel Nijland, Arjan Diepstra, Marie Jose Kersten, Steven Pals, Arjen Cleven, Joost Vermaat
Journal: Blood (2017)
Epithelial maturity influences EPEC-induced desmosomal alterations
Authors: Jennifer Lising Roxas, Gayatri Vedantam, V.K. Viswanathan
Journal: Gut Microbes (2018)

Desmosomes are junctional protein complexes that confer strong adhesive capacity to adjacent host cells. In a recent study, we showed that enteropathogenic Escherichia coli (EPEC) disrupts desmosomes, weakens cell-cell adhesion and perturbs barrier function of intestinal epithelial (C2BBe) cells. Desmosomal damage was dependent on the EPEC effector protein EspH and its inhibitory effect on Rho GTPases. EspH-mediated Rho inactivation resulted in retraction of keratin intermediate filaments and degradation of desmosomal cadherins. Immunofluorescence studies of EPEC-infected C2BBe cells revealed keratin retraction towards the nucleus coincident with significant cytoplasmic redistribution of the desmosomal cadherin desmoglein-2 (DSG2). In this addendum, we expand on how EPEC-induced keratin retraction leads to loss of DSG2 anchoring at the junctions, and show that maturity of the epithelial cell monolayer impacts the fate of desmosomes during infection.
Racial comparison of income, survival, co-morbidities and Trastuzumab therapy among Her 2+ women with metastatic breast cancer (MBC).
Authors: Sreejata Raychaudhuri, Margaret Q. Rosenzweig, Amin Khan, Adam Brufsky
Journal: Journal of Clinical Oncology (2018)

e18673 Background: National breast cancer (BC) racial survival disparity is often attributed to BC subtype differences, even with MBC, with diminished focus on therapy disparity and social determinants of health. Among Her 2+ women with MBC we explored and racially compared: 1. MBC Trastuzumab treatment utilization and time to initiation from MBC diagnosis 2. MBC survival from date of MBC diagnosis 3. Income and co-morbidities Methods: Among a cohort of 1400 patients with MBC (1999-Present), Her 2+ Black and White patients were matched 1:2 for age (within 5 years), ER status and MBC diagnosis date (divided by three into 6-year intervals). Comparison of: 1) Income - US Census zip code's median income, 2) Co-morbidities - Simplified Co-morbidity Score (SCMS) (0-20), 3) Adherence: Trastuzumab initiation (yes/no), 4) Time to initiation of Trastuzumab therapy (months) and 5) MBC survival (months) were compared. Chi square and t test used. Results: N = 24 Black; N = 48 White. Black - significantly worse annual income ($42.5 vs. $64.1; p = .000), co-morbidity scores (6.82 vs 2.73; p = .001), and worse survival (33.8 months vs. 48.2 months; p = .09). Survival (27.9 months vs 50.1 months) was significantly (p = .001) worse for black patients when diagnosed with MBC at age 50 or above. Fewer Black 8/22 (60%), (n = 2 unknown) vs. White 40/45 (89%), (n = 3 unknown) patients received Trastuzumab therapy (p < .05). No racial difference in time to Trastuzumab therapy initiation among patients receiving therapy. Conclusions: Tumor subtypes are not the exclusive etiology of MBC survival disparity as survival differences persist among this subtype matched cohort. Income, age, co-morbidities and disparate treatment may be important causative etiologies of racial survival disparity among women with Her 2+ MBC.
Phase II trial of cetuximab and radiation in low risk, HPV positive patients with locally advanced squamous cell carcinoma of the oropharynx (SCCOP).
Authors: Paul Swiecicki, Emily Light Bellile, Kelly M Malloy, Andrew G Shuman, Chaz Stucken, Matthew E Spector, Douglas Brian Chepeha, Keith Casper, Scott A McLean, Jeffrey Moyer, Gregory T. Wolf, Mark E Prince, Carol Rossier Bradford, Thomas E. Carey, Avraham Eisbruch, Francis P. Worden
Journal: Journal of Clinical Oncology (2016)

6084 Background: We designed a single arm phase II trial to determine the efficacy and toxicity of concurrent cetuximab (C) radiotherapy (RT) in patients with low risk SCCOP. Low risk was defined by tumor stage ( < T4, N3), Human Papilloma Virus-16 positive, and < 10 pack year smoking history. Primary endpoint was rate of recurrence.Methods: 38 patients (pts) with stage III/IVA were enrolled. The median age was 58.5 years (range: 44-76), 87 % males, 13% females; 97 % Caucasian; 88% ECOG 0, 12% ECOG 1. All patients received C 400 mg/m2 day (d) 0 then 250 mg/m2 d 7 and weekly during RT. Pts were treated with a planned 70 Gray (Gy) in 35 fractions over 7 weeks to the gross tumor and 50-60 Gy to subclinical target volumes. Results: As of January 2016 with a median follow up of 20.2 months, 38 pts were evaluable. One pt recurred with distant metastases and died 11 months post C-RT. Median PFS and OS have not been reached. Grade 3 treatment related toxicities were seen in 23 pts (60%), no grade 4 toxicities were seen. The most common grade 3 toxicities included mucositis (12 pts), dehydration (5 pts), dysphagia (4 pts), and leukopenia (4 pts). Twelve (32%) patients had at least one dose of C omitted, primarily due to toxicity. Conclusions: Patients with low risk, HPV positive SCCOP, treated with C + RT, achieve excellent control of disease, though the acute toxicity profile appears to be more significant when compared to historical controls with platinum and radiation. Clinical trial information: NCT01663259.
Investigation of discordant sibling pairs from hereditary breast cancer (HBC) families.
Authors: Kara Landry, David Seward, Julie Dragon, Wendy McKinnon, Laura S Colello, Joann Sweasy, Susan Wallace, Melissa Cuke, Marie Wood
Journal: Journal of Clinical Oncology (2018)

1538 Background: Women who undergo testing for hereditary breast cancer (HBC) may be offered a panel of up to 40 genes but the majority of women tested have no mutation identified on these panels. This implies the existence of additional genes associated with HBC. Using a family-based design, our goal is to identify novel gene(s) or variants associated with HBC. Methods: We enrolled discordant sister pairs (one with and one without breast cancer) from families with ≥3 breast cancers (one diagnosed ≤50) on an IRB approved study. Germline DNA was extracted and whole exome sequencing performed. In order to highlight variants identified by our sequencing analysis as putative risk alleles, we used publicly available bioinformatics tools and genomic databases. By combining information across these resources, we generated a list of candidate risk alleles. Discordant allele scores were calculated for each of the variants (from genes with known cancer associations, and variants likely to alter function) seen in ≥1 case but no controls. Variants were flagged for further study if they were 1. predicted to alter function (using publicly available data bases), 2. located in a cancer associated gene, and 3. seen at low frequency ( < 1%) in the general population. Results: We enrolled 22 sister pairs with a mean age of diagnosis for sisters with breast cancer being 44 (range 34-60, only 1 > 55). More than 50% of families have > 3 cases of breast cancer. We have sequence data from germline exomes from 14 sib-pairs. Analysis has revealed several rare variants in genes not previously associated with HBC (ECO1, RECQL4, PMS1, MYC, UBE2D4). Additionally, 8 rare variants in three known HBC genes (BRCA1, CTNNA1, PMS2), but not reported in current databases (i.e. ClinVar), were identified. Co-segregation analysis of these families is underway. Conclusions: Using a family-based design we have identified both novel genes and novel variants in known HBC associated genes, in affected sisters from HBC families. These findings may represent private variants associated with HBC or support emerging hypotheses that accumulation of variants in cancer risk associated genes may account for HBC. Future studies will evaluate the functional significance of these variants.
Clinical behavior of stage IVC squamous cell carcinoma of the head and neck.
Authors: Vanessa Wookey, Adams Kusi Appiah, Avyakta Kallam, Vinicius Ernani, Lynette Smith, Apar Kishor Ganti
Journal: Journal of Clinical Oncology (2017)

e17511 Background: Squamous cell carcinoma of the head and neck (HNSCC) with distant metastasis at diagnosis (stage IVC) is rare, and outcomes are often lumped together with those of patients who relapse following initial treatment. We evaluated prognostic factors in patients presenting with stage IVC HNSCC. Methods: Data was extracted from the National Cancer Database to determine prevalence, overall survival (OS), and prognostic factors of stage IVC HNSCC (oral cavity, gum, lip, oropharynx, tongue, tonsil and hypopharynx) in adults, using SAS software for analysis. OS curves were estimated using the Kaplan-Meier method and differences were compared using a log-rank test. Significant parameters in the univariate Cox proportional hazards regression model analyses were included in the multivariate model, and hazard ratios, p-values and 95% confidence intervals were presented. Results: Of 226,302 patients with HNSCC, 5458 had distant metastases at diagnosis (2.40%); 5238 had complete data and were included in further analyses. Median survival of the entire cohort was 9.07 months, and one-year survival was 41%. Age &gt; 70 years, Black race and higher Charlson-Deyo comorbidity score were associated with worse OS, while HPV positive status, tonsil and tongue (not including base) primary, private insurance and receipt of any treatment were associated with improved OS on univariate analysis. In multivariate analysis, HPV positive tumors were associated with improved OS compared to HPV negative tumors (HR 0.63, 95% CI 0.48-0.82; p= 0.001), even after adjusting for site of tumor origin. Only patients with a Charlson-Deyo score of ≥2 had worse OS compared to those without comorbidities. Hypopharynx, lip, tonsil and base of tongue primaries had significantly worse OS compared to gum and other mouth. Except for radiation alone and radiation with surgery, treatment demonstrated significant improvement in OS compared to no treatment, a combination of chemotherapy, radiation and surgery provided the largest survival benefit (HR 0.23, 95% CI 0.20-0.28). Conclusions: HPV positivity seems to predict for better prognosis, regardless of site of origin. Patients with metastatic HNSCC should be offered multimodality therapy in order to improve outcomes.
Child vaccination rates drop in England as MMR uptake falls for fourth year
Authors: Jacqui Wise
Journal: BMJ (2018)

Coverage has declined in nine of 12 vaccinations given routinely to children in England, latest figures show.1

The report from NHS Digital shows that coverage of the measles, mumps, and rubella (MMR) vaccine for children reaching their 2nd birthday fell for the fourth successive year. Uptake was 91.2% in England in 2017-18, down from 91.6% in 2016-17 and the lowest level since 2011-12.

The World Health Organization’s target for MMR vaccination is 95%. The latest figures come as outbreaks of measles continue around Europe. More than 41 000 children and adults were infected with measles …
A preliminary investigation of a new detection technology for breast cancer prognosis.
Authors: Hongmei Tao, Yue Lin, Xuedong Du, Xing Tang, Da Lou, Chris Chang Yu
Journal: Journal of Clinical Oncology (2016)

e23176 Background: The diagnostic accuracy of Cancer Differentiation Analysis (CDA) Technology has been evaluated and verified in previous studies (Abstract No. e12578, e22171, e12587, and e15059). The aim of this study is to investigate the potential capability of CDA technology for breast cancer prognosis. Methods: Blood samples (n = 45) collected from 3 breast cancer cases during the course of post-operative treatment (POT) were tested by CDA technology. Information of the cases includes clinical stage, histology, treatment protocols (TP) and so on. Due to the small sample size and different clinical conditions, data were analyzed individually. Based on the time of POT, CDA data for each case were grouped into 3 categories, before, during and after POT. The average CDA values were calculated and compared with different treatment effect evaluation (TEE) (table 1). CDA value ≥ 50 (rel. units) indicates high risk region, and 44 – 50 (rel. units) suggests region for close follow-up. Results: Case A endured three TP, including four cycles of second-line chemotherapy, two cycles of endocrine therapy and five cycles of GP regimen because of repeated PD evaluation from 3/12/2014 to 2/1/2015, although a brief PR was reported after the second second-line chemotherapy. The average CDA of this case was 51.33 before and 56.98 after POT. Case B had five cycles of DX regimen between 8/29/2014 and 12/26/2014, and her TEE was PR after two cycles of DX regimen. Her average CDA was 55.30 before and 50.45 after POT. Case C had four cycles of DC regimen and twice antibody trastuzumab. Her average CDA was 58.16 before and 48.80 after POT. Conclusions: CDA values appear to be declined after POT if the individuals show favorable response to the treatment, but remain high post-operative if the individuals do not respond well to POT. These preliminary data suggest that CDA technology may be useful for monitoring breast cancer patient's response to POT. More studies are needed to validate our findings. Case Age Time period Before POT During POT After POT TEE Sample size Average CDA Sample size Average CDA Sample size Average CDA A 58 3/12/2014 – 2/1/ 2015 10 51.33 10 54.23 2 56.98 PD B 67 8/29/2014 – 12/ 26/2014 4 55.30 8 49.22 1 50.45 SD C 30 11/5/2014 – 1/ 21/2015 6 58.16 / / 4 48.80 SD
Abstract 18881: New Oral Anticoagulants for Periprocedural Management of Anticoagulation in Patients Undergoing Radiofrequency Catheter Ablation for Atrial Fibrillation: a Meta-analysis
Authors: Abdul Shokor Parwani, Daniel Blaschke, Alexander Wutzler, Martin Huemer, Phillip Attanasio, Leif-Hendrik Boldt, Wilhelm Haverkamp
Journal: Circulation (2014)

Introduction: Thromboembolic events are the most feared complication of radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). The traditional periprocedural anticoagulation approach is discontinuation of vitamin K antagonist and bridging with heparin. Newly procedures are done under therapeutic INR 2-3. Recent studies used periprocedural new direct oral anticoagulants (NOACs). Hypothesis: We evaluated the available evidence on the efficacy and safety of NOACs for periprocedural anticoagulation during RFCA of AF. Methods: Pubmed, Embase and Cochrane Central were searched. Retrospective and prospective studies published as peer-reviewed full-size articles were included if they reported embolic events and major and minor bleeding. Results: Fifteen studies were identified (14 observational studies, 1 small randomized trial). A total of 7050 patients were included (NOACs group: 2887 ). A total of 37 thromboembolic complications occurred (0,5%) with 17 events in the NOAC group (0,6%) and 20 in the warfarin group (0,5%) (odds ratio 0.97, 95% confidence interval (CI) 0.48 to 1.99). Major bleeding were numerically higher in the warfarin group compared to the NOACs group. However, the difference did not reach statistical significance (odds ratio 0.69, CI 0.43 to 1.10). Subgroup analysis did not reveal any differences in event rates. Conclusions: Our review suggests that dabigatran etexilate and rivaroxaban are as effective and safe as warfarin for periprocedural anticoagulation in patients undergoing RFCA of AF. However, it has to be acknowledged that the current evidence is mainly based on observational studies.
Pyrexia in an older man, months after emergency
Authors: S M Moledina, A Dimarco, H Sinclair, S Arianayagam
Journal: BMJ (2018)

An 85 year old caucasian man presented to hospital with a three day history of feeling generally unwell. He had undergone emergency endovascular aortic aneurysm repair five months before presentation and had made a poor recovery, regaining limited function. On examination, he was febrile and drowsy with a Glasgow coma scale score of 13. Blood tests showed an elevated C reactive protein (250 mg/L, reference range <4) with a normal leucocyte count. His serum creatinine was 151 mmol/L (59-104) and albumin was 19 g/L (34-50). High sensitivity troponin I was raised at 2823 ng/L (<50), and there were no electrocardiographic changes suggestive of myocardial ischaemia and no history of chest pain. These features are suggestive of a type 2 myocardial infarction; however, blood cultures grew Staphylococcus aureus . The man underwent a computed tomography scan (fig 1).



Fig 1 
Computed tomography scan slice at the level of the aortic graft shows gas bubbles (arrow) in the peri-graft space





### 1. What is the most likely diagnosis?

The air bubbles around the vascular graft indicate endovascular graft infection. This is most commonly associated with Staphylococcus aureus or Staphylococcus epidermidis , and can lead to infective endocarditis. Consider intraoperative contamination, haematogenous spread, and postoperative colonic ischaemia as potential causes. Other sources of Staphylococcus bacteraemia include cellulitis, pneumonia, osteomyelitis, and discitis. Predisposing factors include immunocompromised status, pre-existing prosthetic material, dialysis, or indwelling venous catheters.

#### Discussion

Endovascular abdominal graft infection is rare, with an incidence of around …
Effect of time to treatment on survival in non-small cell lung cancer.
Authors: Trisari Anggondowati, Apar Kishor Ganti, Shinobu Watanabe-Galloway, Gleb Haynatzki, K. M Islam
Journal: Journal of Clinical Oncology (2016)

8542 Background: Time to treatment onset in newly diagnosed cancer patients is associated with increased patient anxiety and if extensively delayed, could affect patients' prognosis. However, evidence in lung cancer is inconclusive. Since waiting time is modifiable, evidence pertaining to its effects is key. This study evaluated the effect of time to treatment on non-small cell lung cancer (NSCLC) survival. Methods: A total of 693,554 patients diagnosed with NSCLC in 2003-2011 were identified from the National Cancer Data Base. Time to treatment was defined as the interval between diagnosis and treatment initiation. Four separate time periods were considered for the analysis: 0 days, 0.1-4.0 weeks (reference), 4.1-6.0 weeks and > 6 weeks. An Extended Cox model was used to predict overall survival by categories of waiting time, adjusted for patient and clinical factors. Results: The association between time to treatment onset and survival varied by stage at diagnosis. In early stage patients who survived at least 36 months, an increased risk of death noted among those who waited for 4.1- 6.0 weeks (HR = 1.06, 95% CI 1.03-1.10), or > 6 weeks (HR = 1.18, 95% CI 1.15, 1.21) to start treatment, compared to those who waited for 0.1-4.0 weeks. Increased waiting time was also associated with increased risk of death among stage III patients who survived for at least 24 months. The hazard ratio for death was 1.06 for patients who started treatment in 4.1-6.0 weeks (95% CI 1.02-1.09) and 1.08 in patients who waited > 6 weeks (95% CI 1.05-1.11). Conversely, in patients who survived < 12 months and stage IV patients, waiting time > 4 weeks was associated with lower risk of death. Same day diagnosis and treatment onset was associated with reduced risk of death, consistent across all stages. Conclusions: Initiating treatment within four weeks of diagnosis appears to be optimal in early stage NSCLC. The association between a shorter waiting time and poor survival in advanced NSCLC likely reflects the biology of the disease, as symptomatic patients with aggressive disease often receive expedited treatment. Treatment delay should be minimized to achieve optimal outcomes in NSCLC patients.