tbuckley/cabot-search huggingface dataset:
Is “watch-and-wait” after chemoradiotherapy safe in patients with rectal cancer?
Authors: Fraser M Smith, Katharine Cresswell, Arthur Sun Myint, Andrew G Renehan
Journal: BMJ (2018)

### What you need to know

Colorectal cancer is the third commonest cancer worldwide.1 About a third of these arise in the rectum. Approximately a third of rectal cancers are locally advanced and at high risk of recurrence. Long-course chemoradiotherapy followed by surgical resection is now standard treatment for these tumours in the UK,23 Europe,4 the US,5 and Australia.6 However, surgery is associated with major complications (up to 15%), perioperative mortality (up to 5%), and the need for a permanent stoma in up to a quarter of patients.7

Within the published literature, after chemoradiotherapy 10-25% of patients have no residual tumour on pathological examination after surgical resection.78910 Clinical examination before surgery in these patients has shown an equivalent favourable response, referred to as a clinical complete response. The criteria for defining a clinical complete response include absence of residual ulceration, stenosis, or mass within the rectum during digital rectal examination and endoscopic examination (fig 1).910



Fig 1 
Endoscopic images of rectum after chemoradiotherapy for rectal cancer show (A) “white” scar (circled) and (B) telangiectasia changes (arrow). Both are accepted as “normal” and are compatible with a clinical complete response



Nearly 15 years ago, a seminal study from a centre in Sao Paulo, Brazil reported that 71 patients with clinical complete response were managed without initial surgery. Instead they were managed by a non-surgical “watch-and-wait” …
TLR9 agonist enhances radiofrequency ablation-induced CTL responses, leading to the potent inhibition of primary tumor growth and lung metastasis 
Authors: Aizhang Xu, Lifeng Zhang, Jingying Yuan, Fatma Babikr, Andrew Freywald, Rajni Chibbar, Michael Moser, Wenjun Zhang, Bing Zhang, Zhaoying Fu, Jim Xiang
Journal: Cellular and Molecular Immunology (2018)
Palliative chemotherapy (CT) with or without cetuximab (CTX) in recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): An Indian retrospective analysis
Authors: A. Bahl, P. Choudhary, K. Bhatia, S. Singhla, G. Shrivastava, J. Bal, A.K. Anand, H. Chaturvedi
Journal: Annals of Oncology (2018)
Seeking informed consent on Brexit
Authors: Tom Moberly
Journal: BMJ (2018)

Despite all the diverging views on Brexit, few people would accuse the government of demonstrating skill, or even competence, in its handling of either negotiations on an exit settlement or preparations for the departure itself.These failings raise the risk that the UK will leave the EU without any deal and that whatever arrangement is reached will be unlikely to satisfy either leavers or remainers.
Extra £3.5bn will fund community and care home services to reduce pressure on hospitals
Authors: Gareth Iacobucci
Journal: BMJ (2018)

The government has pledged to allocate an extra £3.5bn (€4bn; $4.5bn) a year in primary and community care by 2023-24 as part of its long term plan for the NHS.

Prime minister Theresa May said the funding, which will be part of the extra £20.5bn the government had pledged for the NHS over the next five years, would increase the overall share of NHS spending on primary and community care and help to reduce pressure on hospitals.

It will fund initiatives such as new 24 hour “rapid response” healthcare teams to provide urgent care and support in the community as an alternative to hospital, and a national scheme to assign teams of healthcare professionals, including GPs and pharmacists, to care homes to provide tailored treatment and …
Potentially serious incidental findings on brain and body magnetic resonance imaging of apparently asymptomatic adults: systematic review and meta-analysis
Authors: Lorna M Gibson, Laura Paul, Francesca M Chappell, Malcolm Macleod, William N Whiteley, Rustam Al-Shahi Salman, Joanna M Wardlaw, Cathie L M Sudlow
Journal: BMJ (2018)

Abstract Objectives To determine prevalence and types of potentially serious incidental findings on magnetic resonance imaging (MRI) in apparently asymptomatic adults, describe factors associated with potentially serious incidental findings, and summarise information on follow-up and final diagnoses. Design Systematic review and meta-analyses. Data sources Citation searches of relevant articles and authors’ files in Medline and Embase (from inception to 25 April 2017). Review methods Eligible studies included prevalence and types of incidental findings detected among apparently asymptomatic adults undergoing MRI of the brain, thorax, abdomen, or brain and body. Data on study population and methods, prevalence and types of incidental findings, and final diagnoses were extracted. Pooled prevalence was estimated by random effects meta-analysis, and heterogeneity by τ 2 statistics. Main outcome measures Prevalence of potentially serious incidental findings on MRI of the brain, thorax, abdomen, and brain and body. Results Of 5905 retrieved studies, 32 (0.5%) met the inclusion criteria (n=27 643 participants). Pooled prevalence of potentially serious incidental findings was 3.9% (95% confidence interval 0.4% to 27.1%) on brain and body MRI, 1.4% (1.0% to 2.1%) on brain MRI, 1.3% (0.2% to 8.1%) on thoracic MRI, and 1.9% (0.3% to 12.0%) on abdominal MRI. Pooled prevalence rose after including incidental findings of uncertain potential seriousness (12.8% (3.9% to 34.3%), 1.7% (1.1% to 2.6%), 3.0% (0.8% to 11.3%), and 4.5% (1.5% to 12.9%), respectively). There was generally substantial heterogeneity among included studies. About half the potentially serious incidental findings were suspected malignancies (brain, 0.6% (95% confidence interval 0.4% to 0.9%); thorax, 0.6% (0.1% to 3.1%); abdomen, 1.3% (0.2% to 9.3%); brain and body, 2.3% (0.3% to 15.4%)). There were few informative data on potential sources of between-study variation or factors associated with potentially serious incidental findings. Limited data suggested that relatively few potentially serious incidental findings had serious final diagnoses (48/234, 20.5%). Conclusions A substantial proportion of apparently asymptomatic adults will have potentially serious incidental findings on MRI, but little is known of their health consequences. Systematic, long term follow-up studies are needed to better inform on these consequences and the implications for policies on feedback of potentially serious incidental findings. Systematic review registration Prospero CRD42016029472.
Completion Rate and Reporting of Mandatory Pediatric Postmarketing Studies Under the US Pediatric Research Equity Act
Authors: Thomas J. Hwang, Liat Orenstein, Aaron S. Kesselheim, Florence T. Bourgeois
Journal: JAMA Pediatrics (2018)

Many medicines prescribed to children have not been studied or formally approved for pediatric use. The Pediatric Research Equity Act of 2003 authorized the US Food and Drug Administration (FDA) to require pediatric clinical studies.To evaluate the characteristics, completion rate, and transparency of study design and results for mandatory pediatric postmarketing studies required under the Pediatric Research Equity Act.A retrospective cohort study was conducted of pediatric postmarketing studies required for new drugs and new indications approved by the FDA between January 1, 2007, and December 31, 2014, with follow-up through December 1, 2017. Information on the status, design, and results of pediatric studies was obtained from publicly available FDA databases and ClinicalTrials.gov, direct communication with the FDA, and searches of MEDLINE, EMBASE, and Web of Science for peer-reviewed publications.Characteristics and transparency of pediatric studies, results reporting (in ClinicalTrials.gov, peer-reviewed literature, or FDA documents), and availability of pediatric information in drug labels. Rates and times to study completion were evaluated using Cox proportional hazards regression models.Between 2007 and 2014, the FDA approved 114 new drugs and new indications for already approved drugs that were subject to Pediatric Research Equity Act requirements. These drugs were associated with 222 required pediatric postmarketing clinical studies. Overall, 75 pediatric studies (33.8%) were completed as of December 1, 2017. The rates of completion were significantly lower for efficacy studies (38 of 132 [28.8%]) compared with pharmacokinetic studies (19 of 34 [55.9%]; adjusted hazard ratio, 0.31; 95% CI, 0.12-0.82). Information on randomization, blinding, comparator, end point, and study size could not be identified for 74 studies (33.3%), and no reason for discontinuation was provided for 29 of the 42 discontinued studies (69.0%). Among the completed studies, the results were reported for 57 (76.0%). At the time of approval, 18 of 114 drug approvals (15.8%) had any pediatric efficacy, safety, or dosing information in their labels. After a median duration of follow-up of 6.8 years (interquartile range, 4.7-9.1 years), 47 of 114 of drug labels (41.2%) had any pediatric information.Only 33.8% of mandatory pediatric postmarketing studies have been completed after a median follow-up of 6.8 years, and most drug labels do not include information important for pediatric use. To improve evidence-based prescribing of medicines to children, more timely completion of pediatric drug studies is needed.
The Prognostic Significance of Soluble Interleukin-2-Receptor, Beta-2-Microgrobulin and Serum Albumin in Patient with Diffuse Large B-Cell Lymphoma in the Rituximab Era
Authors: Norihito Inoue, Masahiro Yokoyama, Yuko Shirouchi, Takanori Fukuta, Anna Nishihara, Yoshiharu Kusano, Hideki Uryu, Yuko Mishima, Noriko Nishimura, Naoko Tsuyama, Kengo Takeuchi, Yasuhito Terui
Journal: Blood (2018)
ANA testing in ‘real life’
Authors: Maria Infantino, Mariangela Manfredi, Paolo Soda, Mario Merone, Antonella Afeltra, Amelia Rigon
Journal: Annals of the Rheumatic Diseases (2018)

The recent article by Pisetsky et al 1 showing data derived from a comparison of different antinuclear antibody (ANA) assays in a cohort of patients with established systemic lupus erythematosus highlighted the critical issue of ANA detection. With great interest, we read the correspondence by van Hoovels et al 2 describing variation in ANA detection by automated indirect immunofluorescence (IIF) analysis and the following letter from Mahler and Auza on the strong need for ANA testing standardisation.3 Nowadays, the IIF on human epithelial cells (HEp-2) is considered the gold standard for ANA testing, but biological and non-biological issues limiting the IIF test are not currently adequately clarified in study literature.4 5 In fact, despite the fact that the IIF method on HEp-2 cells has existed for about 40 years, there are little data on this topic, and studies are mainly focused on selected patient groups, rather than samples from ‘real …
Inhibitory effects of alantolactone, a naturally occurring sesquiterpenoid, on the growth of human colon cancer cells
Authors: Hye-Young Min, Hyen Joo Park, Hwa-Jin Chung, Jong-Won Lee, Moon-Sun Kim, Eun-Jung Park, Sang Kook Lee
Journal: Cancer Research (2004)

1391   A line of evidence suggests that the overproduction of prostaglandins (PGs) or nitric oxide (NO) are involved in various pathophysiological processes including inflammation and carcinogenesis, and inducible isoforms of cyclooxygenase (COX-2) and nitric oxide synthase (iNOS) are mainly responsible for the production of large amounts of these mediators. Thus, compounds that inhibit the activity or expression of COX-2 or iNOS might be an important target for cancer chemoprevention or antiinflammation. In our previous study, alantolactone, a natural sesquiterpenoid isolated from plant extracts, exhibited the inhibition of PGE 2  and NO production induced by COX-2 and iNOS, respectively, and suppressed the COX-2 and iNOS gene and protein expression and the effects were mediated by the modulation of NF-κB signaling in LPS-stimulated mouse macrophage cells. With the potential suppression of COX-2 and iNOS by alantolactone, in the present study, we further envisaged whether the compound might control the growth of human cancer cells. Alantolactone inhibited cell proliferation of several human colon cancer cells in a time- and dose-dependent manner. Cell cycle analysis by flow cytometry showed that alantolactone induces G2/M cell cycle arrest, and subsequently increases the Sub-G1 peak in HCT 116 colon cancer cells. Alantolactone possessed the induction of p53 expression in a dose-dependent manner, indicating the possible involvement of p53 on the inhibition of cancer cell growth. In addition, alantolactone exhibited to affect the apoptosis-related protein expressions such as the induction of p21, modulation of cyclin B1, and induction of cleavage of poly(ADP-ribose) polymerase (PARP). Alantolactone (10 μM) also inhibited serum-stimulated ERK phosphorylation in the early time. Further studies are underway to explore the exact mechanism of action of alantolactone on the inhibition of cancer cell growth in relation to the modulation of apoptotic biomarkers and signal transduction. These results suggest that the growth inhibitory effects of cancer cells by alantolactone might be related to the induction of G2/M cell cycle arrest and induction of apoptosis along with COX-2 and iNOS suppression, and thus alantolactone might be a potential candidate for further developing cancer chemopreventive agent.
Safety, Efficacy, and Biomarkers of Response to Azacitidine (AZA) with Nivolumab (Nivo) and AZA with Nivo and Ipilimumab (Ipi) in Relapsed/Refractory Acute Myeloid Leukemia: A Non-Randomized, Phase 2 Study
Authors: Naval G. Daver, Guillermo Garcia-Manero, Sreyashi Basu, Jorge E. Cortes, Farhad Ravandi, Tapan M. Kadia, Marina Y. Konopleva, Elias J. Jabbour, Courtney D. DiNardo, Rita Assi, Sherry A. Pierce, Yesid Alvarado, Zeev E. Estrov, Naveen Pemmaraju, Koichi Takahashi, Jing Ning, Graciela M. Nogueras González, Steven M. Kornblau, Mansour Alfayez, Jairo Matthews, Wilmer Flores, Jorge Blando, James P Allison, Padmanee Sharma, Hagop M. Kantarjian
Journal: Blood (2018)
Integration of phospholipid-drug complex into self-nanoemulsifying drug delivery system to facilitate oral delivery of paclitaxel
Authors: Dawei Ding, Bingjun Sun, Weiping Cui, Qin Chen, Xuanbo Zhang, Haotian Zhang, Zhonggui He, Jin Sun, Cong Luo
Journal: Asian Journal of Pharmaceutical Sciences (2018)

Self-nanoemulsifying drug delivery system (SNEDDS) has emerged as a promising platform to improve oral absorption of drugs with poor solubility and low permeability. However, large polarity molecules with insufficient lipid solubility, such as paclitaxel (PTX), would suffer from inferior formulation of SNEDDS due to poor compatibility. Herein, phospholipid-drug complex (PLDC) and SNEDDS were integrated into one system to facilitate oral delivery of PTX. First, PTX was formulated into PLDC in response to its inferior physicochemical properties. Then, the prepared PLDC was further formulated into SNEDDS by integrating these two drug delivery technologies into one system (PLDC-SNEDDS). After PLDC-SNEDDS dispersed in aqueous medium, nanoemulsion was formed immediately with an average particle size of ∼30 nm. Furthermore, the nanomulsion of PLDC-SNEDDS showed good colloidal stability in both HCl solution (0.1 mol/l, pH 1.0) and phosphate buffer solution (PBS, pH 6.8).
An international study on the use of peroral endoscopic myotomy (POEM) in the management of esophageal diverticula: the first multicenter D-POEM experience
Authors: Juliana Yang, Xianhui Zeng, Xianglei Yuan, Kenneth Chang, Omid Sanaei, Lea Fayad, Vivek Kumbhari, Vikesh Singh, Anthony Kalloo, Bing Hu, Mouen Khashab
Journal: Endoscopy (2018)

Abstract Background The aim of this study is to report a novel, multicenter experience with the diverticular peroral endoscopic myotomy (D-POEM) technique in the management of esophageal diverticula. Methods This is a multicenter, international, retrospective study involving three centers. D-POEM was performed using the principles of submucosal endoscopy. Results A total of 11 patients with an esophageal diverticulum (Zenker’s 7, mid-esophagus 1, epiphrenic 3) were included. The mean size of the esophageal diverticula was 34.5 mm. The overall technical success rate of D-POEM was 90.9 %, with a mean procedure time of 63.2 minutes. There were no adverse events. Clinical success was achieved in 100 % (10 /10), with a decrease in mean dysphagia score from 2.7 to 0.1 (P &lt; 0.001) during a median follow-up of 145 days (interquartile range 126 – 273). Conclusion Endoscopic management of esophageal diverticula using the novel technique of D-POEM appears promising. This first case series on D-POEM suggests that the procedure is feasible, safe, and effective in the management of esophageal diverticula. D-POEM offers the distinct advantage of ensuring a complete septotomy. Larger studies are needed to confirm these intriguing results.
Revised diagnostic criteria for plasma cell leukemia: results of a Mayo Clinic study with comparison of outcomes to multiple myeloma
Authors: Praful Ravi, Shaji K. Kumar, Lindsey Roeker, Wilson Gonsalves, Francis Buadi, Martha Q. Lacy, Ronald S. Go, Angela Dispenzieri, Prashant Kapoor, John A. Lust, David Dingli, Yi Lin, Stephen J. Russell, Nelson Leung, Morie A. Gertz, Robert A. Kyle, P. Leif Bergsagel, S. Vincent Rajkumar
Journal: Blood Cancer Journal (2018)

Abstract The current definition of plasma cell leukemia (PCL)— ≥ 20% circulating plasma cells (CPCs) on peripheral smear and plasma cell count ≥ 2 × 10 9 /L—may be too stringent. We reviewed outcomes of 176 multiple myeloma (MM) patients diagnosed between 1971 and 2016, and who had CPCs detectable at diagnosis, to determine whether a lower threshold could be used to diagnose PCL. Median overall survival (mOS) was 1.1 years (95% CI 0.8–1.4) and was similar between patients with &lt; 5% ( n = 54, mOS = 1.4 years [0.7–2.0]), 5–19% ( n = 63, mOS = 1.1 years [0.7–1.4]), and ≥ 20% CPCs ( n = 59, mOS = 1.1 years [0.7–1.5], p = 0.349). As survival was similar between those with 5–19% and ≥ 20% CPCs, we stratified patients by &lt; 5% (mOS = 1.4 years [0.7–2.0]) and ≥ 5% CPCs (mOS = 1.1 years [0.8–1.4], p = 0.154). Outcomes of those with ≥ 5% CPCs were much poorer when compared with a cohort of MM patients diagnosed between 1971 and 2016, who did not have CPCs at diagnosis ( n = 9724, mOS = 4.4 yrs [4.3–4.5], p &lt; 0.001); survival was also lower in patients diagnosed after 2001 with ≥ 5% CPCs ( n = 62, mOS = 1.4 years [0.8–2.5]) compared with patients with standard risk ( n = 1326, mOS = 7.5 years [7.0–8.7]) and high-risk MM ( n = 381, mOS = 4.3 years [3.5–4.9], p &lt; 0.001). We therefore propose that the definition of PCL be revised to patients with ≥ 5% CPCs on peripheral blood smear, who otherwise meet diagnostic criteria for MM.
TCOG T1308 study: The final results of a phase II trial of modified gemcitabine plus S-1 combination as the first-line treatment in patients with advanced biliary tract cancer
Authors: N.-J. Chiang, L.-T. Chen, J.-S. Chen, S.-H. Yang, C. Hsu, Y.-S. Shan, C.-J. Yen, M.-H. Chen, H.-H. Tsou
Journal: Annals of Oncology (2018)
Abstract 15394: Novel Apolipoprotein E-derived ABCA1 Agonist Peptide (CS-6253) Promotes Reverse Cholesterol Transport in vitro and Induces de novo Formation of Apoa-I Containing preβ-1 HDL in Human Plasma
Authors: Anouar Hafiane, John K Bielicki, Jan O Johansson, Jacques Genest
Journal: Circulation (2014)

Modulation of the reverse cholesterol transport (RCT) pathway may provide a therapeutic target for the prevention and treatment of atherosclerotic cardiovascular disease. We evaluated a 26 amino ac...
Hematopoietic stem cell transplantation for adult patients with isolated <i>NPM1</i> mutated acute myeloid leukemia in first remission
Authors: Xavier Poiré, Myriam Labopin, Emmanuelle Polge, Didier Blaise, Patrice Chevallier, Johan Maertens, Eric Deconinck, Edouard Forcade, Alessandro Rambaldi, Gabriela M. Baerlocher, Tsila Zuckerman, Liisa Volin, Harry C. Schouten, Norbert Ifrah, Mohamad Mohty, Jordi Esteve, Arnon Nagler
Journal: American Journal of Hematology (2018)

Acute myeloid leukemia (AML) in first remission (CR1) with isolated NPM1 mutation (iNPM1m) is considered a good prognosis genotype, although up to one-third relapse. To evaluate the best transplant strategy, we retrospectively compared autologous stem cell transplantation (auto-SCT), related (MSD), and fully matched unrelated (MUD) allogeneic stem cell transplantation (allo-SCT). We identified 256 adult patients including 125 auto-SCT, 72 MSD, and 59 MUD. The 2-year leukemia-free survival (LFS) was 62% in auto-SCT, 69% in MUD, and 81% in MSD (P = .02 for MSD vs others). The 2-year overall survival (OS) was not different among auto-SCT, MUD, and MSD, reaching 83% (P = .88). The 2-year non-relapse mortality (NRM) was 2.5% in auto-SCT and 7.5% in allo-SCT (P = .04). The 2-year cumulative incidence of relapse (RI) was higher after auto-SCT (30%) than after MUD (22%) and MSD (12%, P = .01). In multivariate analysis, MSD versus auto-SCT but not MUD versus auto-SCT was associated with lower RI (P < .01 and P = .13, respectively) and better LFS (P = .01 and P = .31, respectively). Age correlated with higher NRM (P < .01). Allo-SCT using MSD appears as a reasonable transplant option for young patients with iNPM1m AML in CR1. Auto-SCT was followed by worse RI and LFS, but similar OS to both allo-SCT modalities.
Abstract 19506: The Differential Effects of Valsartan/Sacubirtril on Cardiac Function in Ischemic versus Dilated Cardiomyopathy: A 1 Year Real World Study
Authors: Avinash K Pandey, Jennifer Reinhart, A. Shekhar Pandey, Subodh Verma
Journal: Circulation (2017)

Background: Improvements in LV ejection fraction (EF) correlates to reduction in morbidity, mortality and hospitalization rates in heart failure (HF) with reduced ejection fraction (HFrEF). Therape...
LncRNAs in polyploid cotton interspecific hybrids are derived from transposon neofunctionalization
Authors: Ting Zhao, Xiaoyuan Tao, Shouli Feng, Luyao Wang, Hui Hong, Wei Ma, Guandong Shang, Shisong Guo, Yuxin He, Baoliang Zhou, Xueying Guan
Journal: Genome biology (2018)

Interspecific hybridization and whole genome duplication are driving forces of genomic and organism diversification. But the effect of interspecific hybridization and whole genome duplication on the non-coding portion of the genome in particular remains largely unknown. In this study, we examine the profile of long non-coding RNAs (lncRNAs), comparing them with that of coding genes in allotetraploid cotton (Gossypium hirsutum), its putative diploid ancestors (G. arboreum; G. raimondii), and an F1 hybrid (G. arboreum × G. raimondii, AD).We find that most lncRNAs (80%) that were allelic expressed in the allotetraploid genome. Moreover, the genome shock of hybridization reprograms the non-coding transcriptome in the F1 hybrid. Interestingly, the activated lncRNAs are predominantly transcribed from demethylated TE regions, especially from long interspersed nuclear elements (LINEs). The DNA methylation dynamics in the interspecies hybridization are predominantly associated with the drastic expression variation of lncRNAs. Similar trends of lncRNA bursting are also observed in the progress of polyploidization. Additionally, we find that a representative novel lncRNA XLOC_409583 activated after polyploidization from a LINE in the A subgenome of allotetraploid cotton was involved in control of cotton seedling height.Our results reveal that the processes of hybridization and polyploidization enable the neofunctionalization of lncRNA transcripts, acting as important sources of increased plasticity for plants.