tbuckley/cabot-search huggingface dataset:
Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Compared to Bortezomib, Thalidomide and Dexamethasone (VTD) As Induction Therapy for the Treatment of Transplant Eligible Multiple Myeloma
Authors: Victor Jimenez-Zepeda, Nizar J. Bahlis, Peter Duggan, Rafael Alonso, Juan José Lahuerta, Antonio Valeri, Paola Neri, Jason Tay, Joaquin Martinez-Lopez
Journal: Blood (2016)
High risk genetic screening program in a community hospital breast imaging center.
Authors: Anne C. Kushwaha, Lilian E Sweeney, Madhumita Ghosh, Banu Arun
Journal: Journal of Clinical Oncology (2017)

1507 Background: The NCCN has published guidelines for screening and testing of Hereditary Breast and Ovarian Cancer (HBOC) that is typically used by the primary physician or oncologist. Little data exists on the value of genetic screening at a major health care access point: the breast imaging center (BIC). Using BICs as potential clinics to identify high risk women could increase the number of appropriate referrals for genetic risk assessment. Therefore, at our hospital-based BIC serving mostly low to middle income patients in a major metropolitan center, we developed a practical screening tool based on the HBOC guidelines and prospectively screened women receiving screening and diagnostic mammography. Methods: A questionnaire based on the NCCN HBOC genetic referral guidelines was added to the intake forms of all patients (pts) obtaining breast imaging at our BIC from 2012 to 2015. Forms were reviewed by the radiologists and flagged if the patient met the guidelines of the tool. Identified pts were contacted by letter and/or telephone and a nurse navigator or genetic counselor verified data, and provided information about genetic counseling to the patient prior to scheduling genetic counseling appointments. Results: Almost 35, 000 pts were seen during the study period. 1214 pts (3.5%) were flagged as possibly high risk, of which 189 pts. had received prior genetic testing. Of the 1025 remaining pts identified as candidates for genetic counseling, 258 (25%) made a genetic counseling appointment and 163 (16%) received genetic counseling. 106 pts. were tested for BRCA1/2. 9 pts (8.5%) tested positive for a BRCA1/2 pathogenic mutation and 8 pts (7.5%) had a Variant of Unknown Significance. Conclusions: Screening for HBOC syndromes at the time of annual breast imaging in a community-based middle to low income metropolitan breast imaging center is practical. Our screening tool identified women with BRCA mutations who would have been otherwise missed. This will have immediate implications for the patient and their family members in regards to increased surveillance and risk reductive surgery discussions.
Increasing burden of liver cancer despite extensive use of antiviral agents in a hepatitis B virus‐endemic population
Authors: Jonggi Choi, Seungbong Han, Namkug Kim, Young‐Suk Lim
Journal: Hepatology (2017)

Most mortalities from liver disease and liver cancer worldwide are attributable to hepatitis B virus (HBV) and hepatitis C virus. Despite remarkable advances in the treatment of HBV over past decades, limited population‐level data are available regarding its impact on burden of liver disease and liver cancer. Mortality data from liver disease and liver cancer were obtained from the national death certificate database of Korea, an HBV‐endemic country, between 1999 and 2013, and were analyzed by Joinpoint analysis. For liver disease, number of annual deaths decreased by 62.3% (95% confidence interval [CI], 62.0‐62.6), crude death rate (CDR) decreased by 64.6% (95% CI, 64.3‐64.9) from 21.2 to 7.5 per 100,000 population, and age‐standardized death rate (ADR) declined by 75.0% (95% CI, 74.7‐75.3), between 1999 and 2013. In contrast, for liver cancer, number of annual deaths increased by 17.8% (95% CI, 17.6‐18.0) and CDR increased by 10.2% (95% CI, 10.0‐10.4) from 20.5 to 22.6, although ADR decreased by 26.9% (95% CI, 26.6‐27.2). The annual number of patients receiving oral antiviral agents against HBV increased from 1,716 to 187,226 during the study period. The increase in mean age at death from liver disease was significantly greater than that from liver cancer (8.8 vs. 6.1 years: P = 0.02). Conclusion : Marked reduction in liver disease mortality by widespread use of antiviral treatments against HBV may increase the life expectancy and number of patients at risk of developing liver cancer, inadvertently leading to increased burden of liver cancer in an HBV‐endemic population. The competing nature between death from liver disease and that from liver cancer should be carefully considered in establishing a health care policy. (H epatology 2017;66:1454–1463).
Doctors can act as advocates on health effects of poverty, says BMA
Authors: Abi Rimmer
Journal: BMJ (2017)

Doctors can help to tackle poverty by highlighting its effects on their patients’ health, the BMA has said.

In a briefing paper published on 20 June, the BMA’s board of science outlined the causes of poverty, how it can affect patient health, and what doctors and the NHS can do to tackle it.1

Parveen Kumar, chair of the board of science, said that doctors were willing to act as advocates for patients on the negative effects of poverty on health and “want to be empowered to support patients who might be living in poverty.”

Recent estimates indicate that a third of people in the UK have, …
60 seconds on . . . the Carlisle method
Authors: Nigel Hawkes
Journal: BMJ (2017)

So we’re told.1 Personally, I’d have guessed far more. But RCTs are the gold standard, so it’s no small matter if among the tens of thousands produced, hundreds can be shown to be questionable by a straightforward method.

John Carlisle, an anaesthetist at Torbay Hospital in Devon, has built himself a parallel career …
Blood biomarker analysis to differentiate between pseudo-progression and true disease progression in post-treatment glioblastoma.
Authors: Bilal Hassan, Kimberly J. Johnson, Jian Li Campian
Journal: Journal of Clinical Oncology (2017)

e13501 Background: Current standard treatment for patients with glioblastoma (GBM) includes glucocorticoid therapy, temozolomide (TMZ), and radiation (RT) which may result in lymphotoxic and immunosuppressive effects. MRI use is currently unreliable in differentiating true from pseudo-progression pathology. Recent studies have suggested that total lymphocyte count (TLC) and CD4 cell count are associated with clinical outcomes. Our objective was to investigate whether TLC or CD4 may help to differentiate treatment effect (pesudoprogression) from tumor progression. Methods: Patients were eligible for this retrospective study if they had 1) GBM diagnosed between February 2010 and July 2015, 2) series of cell counts and clinical follow-ups monitored at Washington University, and 3) tumor progression documented by MRI and pathology. The data were analyzed using descriptive statistics, chi-square tests, Kaplan-Meier survival curves, and progression-free survival. Results: A total of 728 charts were reviewed, of which 45adults met eligibility criteria. The median age and KPS scores were 58 years and 80, respectively. MGMT was detected in 33% of patients and 69% of patients had undergone a gross total resection. Median TLC at baseline was 1700 cells/mm3 (range 400-3100). After the completion of RT/TMZ, TLC dropped 41% to a median of 1000 cells/mm3 (range 200-2900). Median TLC was 1000 cells/mm3 (range 300-2900) at the first MRI documented progression. Patients underwent surgery for this MRI documented progression. Pathology revealed that 62% of patients had true tumor progression, 33% had mixed treatment effect and residual tumor, and 4% had necrosis. The median time from diagnosis to progression was 15 months. There were no statistically significant differences in overall survival or progression free survival found in patients with higher vs lower TLC at baseline, completion of RT/TMZ, and time of progression. Conclusions: These preliminary results do not indicate that TLC level in GBM patients can differentiate between true disease progression and pseudo-progression. A larger sample size that includes patients with CD4 data is needed to confirm these results.
Association between breast cancer recurrence with immunosuppression in immune-mediated disease: A cohort study.
Authors: Ronac Mamtani, Amy Sanders Clark, Frank I. Scott, Colleen Brensinger, Ben Boursi, Lang Chen, Fenglong Xie, Huifeng Yun, Mark T Osterman, Jeffrey R Curtis, James D. Lewis
Journal: Journal of Clinical Oncology (2016)

e13042 Background: Breast cancer recurrence may be promoted by immunosuppression due to decreased immune surveillance. Among patients with immune-mediated disease and previously treated breast cancer, we examined rates of breast cancer recurrence with use of methotrexate, thiopurines, and anti-TNF therapy. Methods: Three retrospective cohort studies within Medicare (2000-2012) included women with rheumatoid arthritis or inflammatory bowel disease who completed surgery for primary breast cancer. Recurrent or second primary breast cancers beyond 365 days from initial surgery were identified. Separate Cox regression models examined risk of cancer recurrence with use of methotrexate, thiopurines, and anti-TNF therapy after surgery, each compared to no use. Analyses were matched on type of breast surgery, and receipt and type of adjuvant therapy. Results: Across all medication groups, 107 women developed breast cancer recurrence during 5,196 person-years. Incidence rates were 20.3 and 19.6 per 1,000 person-years in methotrexate users and nonusers, 32.3 and 17.6 in thiopurine users and nonusers, and 22.3 and 19.5 in anti-TNF users and nonusers, respectively. There was no significantly increased risk of breast cancer recurrence with use of methotrexate (adjusted hazard ratio [HR] 1.07, 95% CI 0.67-1.69), anti-TNF therapy (HR 1.13, 95% CI 0.65-1.97), or thiopurines (HR 2.10, 95% CI 0.62-7.14). Conclusions: Among women with immune-mediated disease and treated breast cancer, there was no significantly increase in the risk of breast cancer recurrence with methotrexate, thiopurine, or anti-TNF therapy, although we cannot rule out a 2-fold or greater increased risk with thiopurines. These data may help clinicians to better assess the risk-benefit relationship when choosing between common immunosuppressants for patients with a history of cancer.
Improvement of TNM Staging for Medullary Thyroid Cancer
Authors: Quan-Yang Duh, Jessica E. Gosnell
Journal: JAMA Surgery (2017)

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Implicit rationing is not open to public scrutiny
Authors: L. H Breimer
Journal: BMJ (1995)

EDITOR,—David Mechanic invokes the Royal Bank of Sweden's prize in economics given in memory of Alfred Nobel to underpin Herbert Simon's apparent favouring of implicit as opposed to explicit rationing.1 Other well known recipients of this prize (endowed in 1968) include F A Hayek and M Friedman. At about the same time as Simon was writing, Hayek identified rationing as a problem that would …
Commensal bacteria exert immunomodulatory activities on human intestinal immune cells
Authors: AM O'Hara, P O'Regan, J MacSharry, C O'Mahony, A Fanning, L O'Mahony, F Shanahan
Journal: Endoscopy (2006)

Aims: Intestinal epithelial cells (IEC) and dendritic cells (DC) play a crucial role in antigen sampling and maintaining gut homeostasis. Here we investigated the responses of these gut cells to commensal and pathogenic bacteria.
Influence des conditions de réalisation d'une capsule endoscopique sur le temps de vidange et le risque de rétention gastrique
Authors: E Ben Soussan, G Savoye, M Antonietti, S Ramirez, E Lerebours, P Ducrotté
Journal: Endoscopy (2006)

Le retard de la vidange gastrique voire la rétention gastrique prolongée est une des limitations de l'exploration par capsule endoscopique. Le but de cette étude rétrospective a été d'évaluer le temps de transit gastrique et grêlique et le nombre d'examens complets (franchissement du cæcum) en fonction des conditions de réalisation de l'examen.
Co-targeting BRAF with mTOR inhibition in solid tumors harboring <i>BRAF</i> mutations: A phase I study.
Authors: Shiraj Sen, Muhammad Rizwan-ul-Haq Khawaja, Soumen Khatua, Daniel D. Karp, Filip Janku, David S. Hong, Javier Munoz, Apostolia Maria Tsimberidou, Wafik Tharwat Zaky, Patrick Hwu, Funda Meric-Bernstam, Vivek Subbiah
Journal: Journal of Clinical Oncology (2016)

2517 Background: Vemurafenib, dabrafenib and trametinib are FDA approved for treating BRAFV600-mutant melanoma. Vemurafenib has activity in multiple BRAFV600-mutant non-melanoma, as well. Unfortunately, patients acquire resistance to BRAF targeted monotherapy. Because preclinical data suggest mTOR activation may mediate resistance, we conducted a phase I study adding mTOR inhibitor everolimus to vemurafenib and evaluated tolerability, maximum tolerated dose (MTD) and response in all patients including those who progressed on prior BRAF targeted monotherapy. Methods: We performed a dose escalation study of vemurafenib twice daily and everolimus daily in 28 day cycles with an expansion cohort treated at MTD. Results: Twenty patients (14 male) with BRAF-mutated tumors (17-V600E, 2-V600K, 1-G469A) were enrolled. 7 had melanoma, 5 had CNS tumors, 4 had thyroid cancer, and 1 each had appendiceal, colorectal, NSCLC, and unknown primary cancer. Median age of 18 adult patients was 64; 2 pediatric patients were 10 and 13. 10 patients had prior therapy with BRAF inhibitor (50%), 10 had prior phase I trial (50%), 18 had surgery (90%), 11 had radiation (55%), 14 had chemo (70%). No DLT was observed with vemurafenib 720 mg BID and everolimus 5 mg QD. 3 patients experienced DLTs (rash, fatigue) when everolimus 10 mg QD was added to vemurafenib. Overall, 13/20 patients (65%) responded: 4 patients (26%) had a partial response, 9 (47%) had stable disease as best response. Of the 10 patients who previously progressed on BRAF inhibitor without mTOR inhibition, 2 had partial response and 4 had stable disease with the addition of everolimus. Two patients with CNS tumors remain on protocol after 7 and 19 cycles. Conclusions: The combination of vemurafenib 720 mg BID and everolimus 5 mg QD is safe, well-tolerated, and has demonstrated activity in patients with BRAF-mutant advanced cancers, including those previously treated with a BRAF inhibitor. Studies to help identify patients warranting up-front dual BRAF/mTOR inhibition are ongoing. Clinical trial information: NCT01596140.
CD3−CD56+ Non-Hodgkin's Lymphomas With an Aggressive Behavior Related to Multidrug Resistance
Authors: Bernard Drénou, Thierry Lamy, Laurence Amiot, Olivier Fardel, Sylvie Caulet-Maugendre, Maryline Sasportes, Jacques Diebold, Pierre-Yves Le Prisé, Renée Fauchet
Journal: Blood (1997)
Діагностичні можливості 200-хвилинного постпрандіального мультиканального інтралюмінального імпеданс-РН-моніторингу стравоходу порівняно з добовим варіантом
Authors: S.H. Melashchenko, V.M. Chernobrovyi, O.O Ksenchyn
Journal: GASTROENTEROLOGY (2020)

24-годинний мультиканальний інтралюмінальний імпеданс-рН-моніторинг (МІІ-рН-моніторинг) стравоходу є найбільш точним методом для виявлення патологічного шлунково-стравохідного рефлюксу у хворих із гастроезофагеальною рефлюксною хворобою (ГЕРХ) та інших станів. Тим не менше деякі дослідники зазначають, що короткотривалий традиційний рН-моніторинг у постпрандіальній фазі також доволі інформативний, але це не було доведено для MII-рН-моніторингу. Мета: оцінка діагностичних можливостей 200-хвилинного постпрандіального MII-рН-моніторингу порівняно з 24-годинним дослідженням. Матеріали і методи. Пацієнти були розділені на 2 групи: 1-ша (гастроезофагеальна рефлюксна хвороба) — 6 жінок і 9 чоловіків, середній вік яких становив (44,8 ± 4,2) року, 2-га (функціональна шлункова диспепсія) — 6 жінок і 7 чоловіків, середній вік яких становив (49,2 ± 3,9) року. Ми окремо проаналізували дані за 200 хвилин дослідження і дані за увесь 24-годинний період. У тестовий період були включені 45 хвилин до провокаційного стандартного сніданку (507 ккал) та 140 хвилин після. Результати. кореляція між показниками обох обстежень була сильною: для кількості кислотних рефлюксів — r = 0,88 (95% довірчий інтервал (ДІ) 0,76–0,95, р &lt; 0,0001); для загальної кількості рефлюксів — r = 0,82 (95% ДІ 0,64–0,92, р &lt; 0,0001). Для часу з рН &lt; 4 кореляція була дещо гіршою — r = 0,69 (95% ДІ 0,41–0,85, р &lt; 0,0001). Обчислення нормативу кількості рефлюксів було проведено за допомогою ROC-кривої. Патологічним рефлюксом вважалась наявність кількості кислих рефлюксів &gt; 6 епізодів протягом 200-хвилинного періоду і &gt; 40 для 24-годинного періоду, загальна кількість рефлюксів &gt; 17 епізодів протягом 200-хвилинного періоду і &gt; 74 для 24-годинного періоду.Висновок. У цілому наші результати демонструють, що 200-хвилинне дослідження може в повній мірі використовуватись для кількісної оцінки гастроезофагеального рефлюксу.
Polymorphisms in <i>TPMT</i> and <i>TYMS</i> may predict severe toxicity in <i>DPYD</i> wild-type patients receiving fluoropyrimidine (FP) chemotherapy for colorectal cancer.
Authors: Aine Mary Peoples, Gul Ahmed, Raimundas Galiauskas, Roisin O Sullivan, Patrick Forde, Prateesh Varughese, Pratheesh Sathyan, Elisabete Amaral-Trusty, Laura McGrath, Kevin P Rosenblatt, Mehdi Dehghani, Kristen C Floyd, Brian Richard Bird, Conleth G. Murphy
Journal: Journal of Clinical Oncology (2016)

e13018 Background: Approx 20% of patients receiving FP chemotherapy experience grade 3-5 toxicity. Known deleterious DPYD mutations account for 20% of these toxicities. We set out to examine whether polymorphisms/mutations in additional candidate genes involved in FP metabolism might account for severe toxicity in DPYD wild type (WT) individuals Methods: All patients receiving FP chemotherapy in our centre are prospectively screened for 4 common DPYD polymorphisms. Colorectal cancer patients treated between 2012-2015 were eligible if they had previously tested DPYD WT. Patients were identified using an institutional database and medical record review. DPYD WT patients who experienced grade 3/4 toxicity were defined as the case population and those without severe toxicity were categorised as the control population. Following informed consent, buccal swabs were taken to obtain DNA samples in order to genotype candidate genes (TPMT, TYMS and MTHFR). Statistical analysis was carried out on the data set returned. Results: 49 patients were recruited, 24 cases and 25 controls. Repeat testing confirmed DPYD WT status in all patients in concordance with previous genotyping. Polymorphisms in other candidate genes were found in both cases and controls. TPMT *1/*3A or *3C polymorphism was present in 6/24 cases and not found in controls (χ2 p = 0.007). Compound heterozygote status (polymorphisms in both the 5’ promoter and 3’ untranslated regions) of the TYMS gene were present in 21/24 cases and 12/25 controls (χ2 p = 0.003). Conclusions: In patients who are DPYD WT, TPMT *1/*3A or *3C may predict severe toxicity. TYMS compound heterozygote status is also associated with severe toxicity. This remained predictive when patients with concurrent TPMT mutations were excluded. These findings should be replicated in larger data sets, ideally in a prospective trial
SPIN90 Depletion and Microtubule Acetylation Mediate Stromal Fibroblast Activation in Breast Cancer Progression
Authors: Eunae You, Yun Hyun Huh, Ahreum Kwon, So Hee Kim, In Hee Chae, Ok-Jun Lee, Je-Hwang Ryu, Min Ho Park, Ga-Eon Kim, Ji Shin Lee, Kun Ho Lee, Yong-Seok Lee, Jung-Woong Kim, Sangmyung Rhee, Woo Keun Song
Journal: Cancer Research (2017)

Abstract Biomechanical remodeling of stroma by cancer-associated fibroblasts (CAF) in early stages of cancer is critical for cancer progression, and mechanical cues such as extracellular matrix stiffness control cell differentiation and malignant progression. However, the mechanism by which CAF activation occurs in low stiffness stroma in early stages of cancer is unclear. Here, we investigated the molecular mechanism underlying CAF regulation by SPIN90 and microtubule acetylation under conditions of mechanically soft matrices corresponding to normal stromal rigidity. SPIN90 was downregulated in breast cancer stroma but not tumor, and this low stromal expression correlated with decreased survival in breast cancer patients. Spin90 deficiency facilitated recruitment of mDia2 and APC complex to microtubules, resulting in increased microtubule acetylation. This increased acetylation promoted nuclear localization of YAP, which upregulated expression of myofibroblast marker genes on soft matrices. Spin90 depletion enhanced tumor progression, and blockade of microtubule acetylation in CAF significantly inhibited tumor growth in mice. Together, our data demonstrate that loss of SPIN90-mediated microtubule acetylation is a key step in CAF activation in low stiffness stroma. Moreover, correlation among these factors in human breast cancer tissue supports the clinical relevance of SPIN90 and microtubule acetylation in tumor development. Cancer Res; 77(17); 4710–22. ©2017 AACR.
The performance of the 21-gene assay standard cutpoints of 18 and 31 in HR+, HER2- invasive breast cancer (BC), while waiting for TAILORx mid-range recurrence score results.
Authors: Dave P. Miller, Valentina I. Petkov, Steven Shak
Journal: Journal of Clinical Oncology (2017)

537 Background: The Recurrence Score (RS) was shown in NSABP B-20 to predict chemotherapy (CT) benefit for RS ≥31 and no CT benefit for RS &lt;18. The TAILORx results for RS &lt;11 (NEJM 2015) reported excellent outcomes with no opportunity for CT to add additional benefit. As we await TAILORx results for RS 11-25, we characterized BC specific mortality (BCSM) for RS groups (cutoffs of 11, 18, 25, and 31) in the population-based SEER study of pts treated based on RS. Methods: RS results were provided to SEER registries per their methods (npj Breast Cancer 2016). Pts diagnosed (Jan 2004 - Dec 2012) with N0 HR+ HER2- negative BC, and no prior malignancy were eligible. BCSM estimates by CT use were computed using standard cutpoints of 18 and 31 and TAILORx cutpoints of 11 and 25. Results: Among 49,681 with a RS, 9,486 (19%) had RS &lt;11, 17,988 (36%) had RS 11-17, 14,541 (29%) had RS 18-25, 3,805 (8%) had RS 26-30, and 3,861 (8%) had RS ≥31. Reported CT use and 5-y BCSM increased with increasing RS. For pts with both RS &lt;11 and RS 11-17, CT use was uncommon and 5-y BCSM was low regardless of CT use. For pts with RS 18-25, CT use was more common and the 5-y BCSM was about 1% regardless of CT use. For pts with RS of 26-30 or ≥31, CT was common, and lower 5-y BCSM was observed with CT reported yes than with CT reported no or unknown. Conclusions: Pts in real-world clinical practice with RS &lt;11, consistent with TAILORx, and pts with RS 11-17 have low 5-y BCSM with limited CT use, supporting hormonal therapy alone for pts with RS &lt;18. The high end of the TAILORx mid-range (18-25) also showed good 5-y BCSM both with and without CT, highlighting the importance of the randomized results of TAILORx. [Table: see text]