tbuckley/cabot-search huggingface dataset:
Childhood energy intake and adult mortality from cancer
Authors: C. Wright, S. J Frankel, D. J Gunnell, T. J Peters, M. Maynard, G. D. Smith
Journal: BMJ (1998)

Early diagnosis allows option of prenatal diagnosis in subsequent pregnanciesEditor-Like Wald and Morris, we do not advocate neonatal screening for cystic fibrosis, although the situation is not as simple as they seem to suggest.The benefits of screening are not limited to early treatment of affected children; early diagnosis allows parents to have the options of prenatal diagnosis in subsequent pregnancies, although only a minority of carrier couples can be detected in this way.
(gamma)-Hydroxybutyrate is a new recreational drug that may lead to loss of consciousness
Authors: I. M Stell, J. M Ryan
Journal: BMJ (1996)

EDITOR,—We were interested in A Richard Green and Guy M Goodwin's editorial on ecstasy and neurodegeneration.1 We wish to draw attention to another recreational drug, which is taken in similar circumstances to ecstasy, whose use can lead to acute neurological effects.

(gamma)-Hydroxybutyrate—also known as GHB, sodium oxybate, GBH, and liquid ecstasy—has been available in Britain since 1994, mostly in night clubs around London. It has recently become more readily available, and the National Poisons …
Self help approach to graded exercise may help chronic fatigue syndrome
Authors: Susan Mayor
Journal: BMJ (2017)

Using a self help approach to graded exercise in combination with specialist medical care reduced fatigue and improved physical function in patients with chronic fatigue syndrome, a randomised trial has shown.1

Chronic fatigue syndrome, characterised by longlasting, disabling fatigue, affects as much as 2.6% of the UK and US populations, and the prognosis is currently poor, as only 5% of patients recover.

The UK National Institute for Health and Care Excellence recommends treatment with graded exercise therapy and cognitive behavioural therapy. But access to specialist therapists for graded exercise programmes is limited, and patients’ organisations have questioned its value, arguing that it can be harmful.

The …
5 year Overall survival of triple negative breast cancer: A single institution experience.
Authors: Savitri Padmanabhan Skandan
Journal: Journal of Clinical Oncology (2016)

e12580 Background: Triple negative breast cancer (TNBC) involves any breast cancer that does not express the genes for estrogen and progesterone receptors (ER /PR) and Her2/neu. TNBC accounts for approximately 10- 20% of invasive breast cancers and this sub-type carries a poorer prognosis. TNBC are also frequently associated with BRCA mutations. We performed a retrospective review of TNBC that were seen at our institution, Lehigh Valley Health Network from 2005 to 2009 for survival and prevalence of BRCA mutation. Methods: Breast Cancer cases that presented to Lehigh Valley Health Network (LVHN) from 2005 to 2009 and which were triple negative, hormone receptors negative/Her2 unknown and hormone receptor/Her2 unknown were retrieved from tumor registry. Records of the above cases were reviewed and only the breast cancer cases that were triple negative were included for the study. Data was collected for age, stage on presentation, treatment received, survival and presence of BRCA mutation if genetic testing was performed. Results: 388 Charts were reviewed and 224 cases were found to be TNBC with age range of 29 to 88 years. Of the TNBC cases, 41 were stage 0, 72 cases were stage 1, 64 cases were stage 2, 24 cases were stage 3 and 23 cases were stage 4 on presentation. Overall 5 year survival rate was 78.6%. The 5 year survival rates stage wise included 92.7% for stage 0, 95.8% for stage 1, 78.1% for stage 2, 54.2% for stage 3 and 26.1% for stage 4. 172 charts were reviewed for genetic testing. 144 cases did not get tested. Out of 32 cases that were tested, 17 had wild type, 9 had BRCA1 mutant and 6 had BRCA2 mutant. Conclusions: 224 triple negative breast cancer cases were seen at LVHN from 2005 to 2009. Majority of cases presented as early stages, stage 0 to II. Age ranges of patients were 29 to 88 years. Overall 5 year survival for TNBC was 78.6%. Prevalence of BRCA mutation is 7.21% of the triple negative breast cancer cases. This is lower than that reported in literature where the prevelance of BRCA mutation is approximately 20% of TNBC. Possible reasons for this variation include age at diagnosis and patients' refusal for testing. Of the patients that were tested the prevalence was 46.88% and may be attributed to additinal high risk features such as age and family history.
The Angiosarcoma Project: Generating the genomic landscape of a rare cancer through a direct-to-patient initiative.
Authors: Corrie Painter, Michael Dunphy, Elana Anastasio, Mary McGillicuddy, Kristin Anderka, Katie Larkin, Niall Lennon, Yen-Lin Chen, Eric Lander, Todd Golub, Nikhil Wagle
Journal: Journal of Clinical Oncology (2017)

1519 Background: Angiosarcoma (AS) is a rare soft tissue sarcoma, with an incidence of 300/yr and a 5-year DSS of 30%. The low incidence has impeded large-scale research efforts that may lead to improved clinical outcomes. To address this, we launched a nationwide study, which seeks to empower patients (pts) to accelerate research by sharing their samples and clinical information remotely. Methods: With pts and advocacy groups we developed a website to allow AS pts to participate across the US. Pts are mailed a saliva and blood draw kit for germline and cell free (cf) DNA analysis. We then obtain medical records and stored tumor samples. Whole exome sequencing will be performed on tumor, cfDNA and saliva samples. Transcriptome analysis will be performed on tumor samples. A clinically annotated genomic database will be generated and shared widely to identify genomic drivers and mechanisms of response and resistance to therapies. Study updates will be shared with pts regularly. Results: We conducted a 3-week pilot study to test the feasibility of enrolling geographically dispersed AS pts through a direct-to-patient (DTP) approach. Through social media, we identified 100+ pts willing to participate, 90 within the first day of outreach. We enrolled 15 pts from 10 states to test our ability to remotely obtain pt reported data, online consent, and samples. The average age of pts is 48, ranging 23-71 yrs. Primary locations of AS are breast 6 pts (40%), cardiac 4 pts (27%), scalp 2 pts (13%), liver 1 pt (6%), bladder 1 pt (6%), forehead 1 pt (6%). 9 pts (60%) reported being disease free, 4 pts (27%) reported having AS spread to lung, lymph, bone, and hip. Requests for medical records and tissue samples are underway, and initial saliva samples have been received. We are now opening this study to all AS pts in the USA. Conclusions: A DTP approach enabled rapid identification of an initial cohort of AS pts willing to share tumors, saliva, blood and medical records. We were able to obtain detailed clinical experiences and samples to perform genomic analysis. This study serves as proof of principle that DTP genomics efforts can democratize cancer research for exceedingly rare cancers, which to date have been disproportionately understudied.
Progress Toward Containment of Poliovirus Type 2 — Worldwide, 2017
Authors: Nicoletta Previsani, Harpal Singh, Jeanette St. Pierre, Liliane Boualam, Jacqueline Fournier-Caruana, Roland W. Sutter, Michel Zaffran
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

The Global Polio Eradication Initiative (GPEI) continues to make progress toward the eradication target. Only one of the three serotypes, wild poliovirus (WPV) type 1 (WPV1), is still circulating, and the numbers of cases and countries with endemic transmission are at record lows. With the certification of wild poliovirus type 2 (WPV2) eradication in 2015 and the global replacement of trivalent oral poliovirus vaccine (tOPV) containing Sabin poliovirus types 1, 2, and 3 with bivalent OPV containing only Sabin poliovirus types 1 and 3 during April-May 2016, poliovirus type 2 (PV2) is now an eradicated pathogen. However, in eight countries (Cameroon, Chad, Democratic Republic of Congo, Mozambique, Niger, Nigeria, Pakistan, and Syria), monovalent type 2 OPV (mOPV2) was authorized for large-scale outbreak control after tOPV withdrawal (1). Poliovirus containment, an evolving area of work that affects every country, aims to ensure that all PV2 specimens are safely contained to minimize the risk for reintroducing the virus into communities. This report summarizes the current status of poliovirus containment and progress since the last report (2), and outlines remaining challenges. Within 30 countries, 86 facilities have been designated by the relevant national authorities (usually the Ministry of Health) to become poliovirus-essential facilities for the continued storage or handling of PV2 materials; each country is responsible for ensuring that these facilities meet all biorisk management requirements.
Trends in mastectomy rates over time in elderly women with stage I, hormone-sensitive breast cancer: A SEER-based study.
Authors: Jose G. Bazan, Marisa A Bittoni, James L Fisher, Julia R. White
Journal: Journal of Clinical Oncology (2016)

1063 Background: Randomized trials and registry data established that breast conservation with lumpectomy (Lump) and breast radiotherapy (RT) yields equivalent cancer outcomes to mastectomy (Mast) for women with early stage breast cancer (BC). Clinical trial data since 2004 increasingly supports that Lump alone compared to Lump+breast RT results in equivalent survival and acceptable cancer control in women ≥ 70 years old with stage I (T1N0) hormone-sensitive (HS) BC on endocrine therapy. Since Lump alone represents sufficient treatment for elderly women with stage I HS BC we hypothesize that Mast rates have decreased in this subgroup. Methods: We used the Surveillance Epidemiology and End Results (SEER) registry data to conduct this study. We included women ≥ 70 years old with T1N0 HS BC classified as ER+ or PR+ from 2000-2012. We compared rates of Mast and Lump (+/-RT) in women diagnosed before 2004 to those diagnosed from 2005-2012. We also examined Lump and Mast rates by race: White, Black, and Asian-Pacific-Islander(API). Statistical analyses were performed using differences in proportions (p < 0.05 considered statistically significant). Results: 87,009 women met the inclusion criteria (N = 30,050 before 2004; N = 56,959 from 2005-2012). Since 2004, Mast rates decreased by 5.2% (95% CI, 4.5%-5.9%) from 32.6% to 27.4% (p < 0.0001). Lump rates increased by 3.4% (95% CI, 2.8%-4.1%) from 66.4% to 69.8% (p < 0.0001). Before 2004, elderly white women were more likely to undergo Lump compared to black (66.8% vs. 62.6%, p = 0.0421) or API women (66.8% vs. 61.6%, p < 0.0001) and less likely to undergo Mast compared to black (32.3% vs. 34.9%, p < 0.0001) or API (32.3% vs. 38.0%, p < 0.0001) women. Since 2004, elderly white women remained least likely to undergo Mast in comparison to black women (26.8% vs. 30.8%, p < 0.0001) or API women (26.8% vs. 33.6%, p < 0.0001). Conclusions: We found a modest decrease in Mast rates in elderly women with stage I HS BC since 2004. However, more than 25% of women in this subgroup continue to undergo Mast. Mast rates are higher in elderly black and API women compared to white women. Further study is warranted to understand why Mast rates did not decline more in this favorable risk population.
A novel approach to detect large indels from targeted sequencing data in clinical cancer setting.
Authors: Lijuan Chen, Caiping Chen, Dongling Chen, Qiuyi Zou, Gungwei Qin, Hui Kang, Ming Yao, Kai Wang
Journal: Journal of Clinical Oncology (2017)

e13002 Background: Next generation sequencing (NGS) technologies have already shown numerous advances to revolutionize our understanding of cancer genomic profiling and improve cancer treatments. There have been many NGS data analysis tools available for identification of different genomic alternations including short insertion and deletion (short indel, &lt; 25 bp in general). However, detection of &gt; 100 bp large indel (L-indel) from short reads (generally &lt; 200 bp) remains a huge challenge. L-indels identified in genes like MET and FLT3 have proven a critical implication in cancer treatments. Moreover, there is an urgent need for an algorithm to validate L-indels generated by genomic modification systems like ZFN, TALENs and CRISPR/Cas9. Methods: A novel algorithm was developed for calling L-indels in targeted sequencing data as following: raw reads were first filtered by selecting high-quality ones and correcting wrong bases; a chunk of contig (unitig) was then assembled and aligned to reference genome; lastly, break point information was collected and L-indels were calculated. The algorithm was applied on the reads generated from NA12878 cell line and FFPE samples collected in our lab respectively on the Illumina platform. Validation were performed by PCR and Sanger sequencing. Results: 22 novel exonic L-indels (17 deletions and 5 insertions) were identified with a median size of 1,616 bp (range: 25-6,684 bp) from NA12878 sequencing data and 100% successfully confirmed by Sanger sequencing. In addition, 6 out of 9 reported L-indels were also found with the rest awaiting for further exploration. Strikingly, a 2,446 bp deletion on MSH6, encodes an important component in mismatch repair (MMR) system, was detected on a FFPE sample of a lung cancer adenocarcinoma, which prompted to consideration of MMR deficiency otherwise. Conclusions: We have developed and validated a novel and accurate method for NGS large indels detection dedicated for targeted sequencing data in clinical cancer setting. Equipment of this method will greatly increase the capability of comprehensively understanding genomic alterations from a single NGS-based assay, and provide more information for potential clinical use.
Effect of adding sequential docetaxel to neoadjuvant epirubicin in treatment of advanced breast cancer: Preliminary results of tumor response.
Authors: Nicolas Ramirez-Torres, Juan Asbun-Bojalil, Christian Moctezuma, Ancizar Perez Puente, Erika Ruiz-García, Cesar Lopez-Camarillo, Laurence Marchat, Jorge A Guadarrama-Orozco, Horacio Astudillo
Journal: Journal of Clinical Oncology (2016)

e12509 Background: The aim of this study was to assess the clinical and pathological response rates to anthracycline containing regimens with or without taxanes as neoadjuvant systemic therapy (NST) in women with locally advanced breast cancer (LABC). Methods: Patients diagnosed with LABC were included. A cohort received 4 cycles of FEC (5-fluorouracil 500 mg/m2, epirubicin 75 mg/m2, cyclophosphamide 500 mg/m2, respectively) every 3 weeks followed by 4 cycles of docetaxel (D) 75 mg/m2 as infusion intravenous (IV) every 3 weeks. Another cohort received 6 cycles of FEC (500 mg/m2, 100 mg/m2, 600 mg/m2, respectively). After the chemotherapy surgery was performed. Results: There was no statistically significant difference in overall response rate (ORR: 78.5% vs 85%; P = 0.299) and clinical complete response (cCR: 20.6% vs 33.3%; P = 0.103) for 4FEC→4D compared to 6FEC, respectively. Instead, there was a statistically significant improved rate of pathological complete response (pCR: 30.2% vs 16.7%; P = 0.049) and negative axillary lymph nodes (51.6% vs 35%; P = 0.03) for 4FEC→4D compared to 6FEC, respectively. Severe toxicity was low and not significant in both cohorts. The logistic regression multivariate analysis showed that main factors to obtain a pCR were stage IIIA (OR, 3.38; P = .002) and type of chemotherapy with 4FEC→4D (OR, 0.39; P = .024). Conclusions: This study showed that 4FEC→4D scheme with conventional dose is highly active and well tolerated for patients with LABC.
3-D Electrochemical Impedance Spectroscopy Mapping of Arteries to Detect Metabolically Active but Angiographically Invisible Atherosclerotic Lesions
Authors: René R. Sevag Packard, Yuan Luo, Parinaz Abiri, Nelson Jen, Olcay Aksoy, William M. Suh, Yu-Chong Tai, Tzung K. Hsiai
Journal: Theranostics (2017)

We designed a novel 6-point electrochemical impedance spectroscopy (EIS) sensor with 15 combinations of permutations for the 3-D mapping and detection of metabolically active atherosclerotic lesions. Two rows of 3 stretchable electrodes circumferentially separated by 120° were mounted on an inflatable balloon for intravascular deployment and endoluminal interrogation. The configuration and 15 permutations of 2-point EIS electrodes allowed for deep arterial penetration via alternating current (AC) to detect varying degrees of lipid burden with distinct impedance profiles (Ω). By virtue of the distinctive impedimetric signature of metabolically active atherosclerotic lesions, a detailed impedance map was acquired, with the 15 EIS permutations uncovering early stages of disease characterized by fatty streak lipid accumulation in the New Zealand White rabbit model of atherosclerosis. Both the equivalent circuit and statistical analyses corroborated the 3-D EIS permutations to detect small, angiographically invisible, lipid-rich lesions, with translational implications for early atherosclerotic disease detection and prevention of acute coronary syndromes or strokes.
BBI608-201GBM: A phase Ib/II clinical study of napabucasin (BBI608) in combination with temozolomide (TMZ) for adult patients with recurrent glioblastoma (GBM).
Authors: Warren P. Mason, Paula de Robles, Laura Borodyansky, Matthew Hitron, Waldo Feliu Ortuzar, Waheed Khan, Bo Xu, Wei Li, Youzhi Li, C J Li
Journal: Journal of Clinical Oncology (2017)

e13525 Background: Napabucasin, a first-in-class cancer stemness inhibitor in clinical development, suppresses cancer stemness by targeting STAT3-driven gene transcription. Pre-clinically, potent and broad-spectrum anti-cancer activity was observed in vitro and in vivo, alone and in combination with other agents. PK studies demonstrated napabucasin penetration in the murine orthotopic GBM model. Methods: A phase Ib/II open-label, multi-center study in pts with GBM at first recurrence who have not received bevacizumab, was performed to determine safety and preliminary activity of napabucasin administered orally at 480mg BID po in combination with TMZ 150mg/m²/day po; days 1 through 5 of each 28 day cycle, until disease progression or unacceptable toxicity. A 6-patient safety cohort was planned to evaluate the occurrence of DLT during the first 28 days of combination treatment with napabucasin and TMZ. 4 additional patients have been enrolled under the RP2D expansion phase. Results: 11 pts have been enrolled to date; no DLT was observed in the safety cohort and the RP2D of the combination is 480 mg BID for napabucasin. The safety profile was consistent with that of each agent as monotherapy and most common AEs included grade 1/2 diarrhea, nausea, abdominal cramps, and vomiting. Two patients requested to withdraw treatment due to concurrent conditions and AE s. 9 patients were evaluable by RANO; Disease Control Rate was observed in 5 patients (55.5%) of which 4 achieved PR (44.4%) and 1 achieved SD (11.1%). The Overall response rate was 44.4% in the evaluable patients. Conclusions: This phase Ib/II study demonstrated that napabucasin at 480 mg BID can be safely combined with temozolomide at full dose and showed encouraging anti-tumor activity in patients with recurrent Glioblastoma. Clinical trial information: NCT02315534. [Table: see text]
Retrospective review of steroid-induced acne in patients with breast cancer.
Authors: Shalini R Krishnasamy, Jae Jung
Journal: Journal of Clinical Oncology (2017)

e12570 Background: With the rapid development of targeted inhibitors, the incidence of cutaneous chemotoxicities is rising and represents a significant cause of morbidity in cancer patients. Therefore, rapid recognition of rashes that warrant dose reduction or discontinuing treatment is critical. Unfortunately, the concomitant use of systemic steroids with chemotherapeutics that can produce acneiform eruptions, make it difficult to distinguish a cutaneous chemotoxicity from systemic steroid induced acne (SSIA). Although SSIA is a well known complication of systemic steroid administration, there are few published studies regarding this condition, none of which have been done in cancer patients. In this study, we sought to examine the incidence of SSIA, the patient and tumor characteristics as well as the chemotherapy regimen most commonly associated with SSIA in breast cancer patients treated with chemotherapy at the City of Hope National Comprehensive Cancer Center. Methods: We performed a retrospective study. Using the institutional registry of patients, we identified 3,848 patients that received a diagnosis of breast cancer between 1/2009-6/2015, 1,991 (51%) of which received at least one cycle of chemotherapy. 61 of these patients received a ICD-9 billing code for “acne” or “ steroid acne”, 10 of whom had explicit documentation of acne or acneiform eruption in their chart. Results: All 10 patients were female with a median age of 49 (range 36-56). 50% of patients had ER + /PR + disease and 30% had ER - /PR - /HER2 - breast cancer. 90% of patients had stage I or II disease. 70% of patients developed steroid induced acne after the 1st cycle of chemotherapy. All regimens contained either docetaxel or paclitaxel. Dexamethasone was implicated in all but one case. We report an overall incidence of SSIA of 0.05% among breast cancer patients treated with at least once cycle of chemotherapy at our institution. Conclusions: These results suggest that breast cancer patients at highest risk for SSIA are on taxane-based regimens with early stage disease and are most likely to develop the reaction after their first cycle of chemotherapy. This study however is limited by the retrospective design, the reliance on ICD 9 billing codes, and the limited sample size.
Contact Precautions for Endemic MRSA and VRE
Authors: Daniel J. Morgan, Richard P. Wenzel, Gonzalo Bearman
Journal: JAMA (2017)

This Viewpoint argues for rescission of legal mandates requiring contact precautions for any patient with methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) infection in favor and more selective and cost-effective infection control measures.