tbuckley/cabot-search huggingface dataset:
Intratumoral <i>Fusobacterium Nucleatum</i> Levels Predict Therapeutic Response to Neoadjuvant Chemotherapy in Esophageal Squamous Cell Carcinoma
Authors: Kensuke Yamamura, Daisuke Izumi, Raju Kandimalla, Fuminori Sonohara, Yoshifumi Baba, Naoya Yoshida, Yasuhiro Kodera, Hideo Baba, Ajay Goel
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Emerging evidence indicates that gut microbiome plays a crucial role in the cancer pathogenesis. Although Fusobacterium nucleatum (F. nucleatum) is associated with poor prognosis in multiple cancers, its clinical significance in predicting response to chemotherapy in patients with esophageal squamous cell carcinoma (ESCC) remains unclear. Experimental Design: The F. nucleatum levels were quantified by qPCR assays in tumor tissues from 551 patients with ESCC from two independent cohorts, including 101 patients who received neoadjuvant chemotherapy prior to curative resection. Associations between F. nucleatum burden and recurrence-free survival (RFS), as well with chemotherapeutic response were evaluated using response evaluation criteria in solid tumors (RECISTs), primary tumor metabolic response defined by maximum standardized uptake value (SUVmax) changes in positron emission tomography-CT (PET/CT), and pathologic tumor regression grade (TRG). Results: High burden of F. nucleatum in patients with ESCC associated with poor RFS in both training [log-rank P = 0.02; HR = 1.61; P = 0.03] and validation cohorts (log-rank P = 0.003; HR = 1.96; P = 0.004). Importantly, patients with ESCC with high levels of F. nucleatum displayed poor chemotherapeutic response for all three evaluation methods: RECIST (P = 0.04), SUVmax change in PET/CT (P = 0.0004), and TRG (P = 0.003). Conclusions: We conclude that high levels of intratumoral F. nucleatum have a prognostic significance for predicting poor RFS in patients with ESCC. More importantly, our data indicates that higher F. nucleatum burden correlates with poor response to neoadjuvant chemotherapy, suggesting the possibility that an antibiotic intervention against this bacterium may significantly improve therapeutic response in patients with ESCC.
DL‐PDT for AK: multicentre trial comparing BF‐200 ALA with MAL
Authors: J.E. Räsänen, N. Neittaanmäki, L. Ylitalo, J. Hagman, P. Rissanen, L. Ylianttila, M. Salmivuori, E. Snellman, M. Grönroos
Journal: British Journal of Dermatology (2019)

Actinic keratoses (AK) are areas of sun‐damaged skin found mainly on parts of the body which have received lots of sun exposure. At first, they can be hard to see, and are more easily felt, being rough, like sandpaper. They may grow to a centimetre or two in diameter. Up to 20% of AKs may progress to a type of skin cancer called squamous cell carcinoma (SCC) within 10 to 25 years. One treatment option is a type of photodynamic therapy called Daylight photodynamic therapy (DL‐PDT) in which a cream, containing a ‘photosensitiser’, is applied to the lesion (affected area of skin). This photosensitiser is, by itself, inactive. However, when light of a certain wavelength shines onto skin to which the photosensitiser has been applied, the photosensitiser is activated and the treatment kills the abnormal cells in the skin. This study aimed to compare the efficacy (how well it works), tolerability (including pain and side effects) and cost‐effectiveness of two types of photosensitizer, called BF‐200 ALA and MAL. Altogether 69 patients with a total of 767 AKs located symmetrically on the face or scalp were treated at three centres in Finland. A single session of DL‐PDT was given in a randomized split‐face design, i.e. one half of the face was treated with one photosensitizer and the other half of the face with the other. The results were assessed at 12 months after treatment by a blinded observer, meaning they did not know which treatment was used on each side. The authors found out that BF‐200 ALA cleared significantly more AKs than MAL (79.7% vs. 73.5%). When comparing the half‐faces per single patient, the clearance of AKs was significantly better for the BF‐200 ALA treated sides than for those treated with MAL. The patient‐reported pain during the light treatment was low for both photosensitizers with no significant difference between them. The treatment‐related skin reactions a week after DL‐PDT were stronger on the sides treated with BF‐200 ALA. The cosmetic outcome (meaning how it looked) at 12 months was excellent or good in >90% of cases with both photosensitizers. The costs of DL‐PDT were similar for both photosensitizers, but the effectiveness was slightly higher for BF‐200 ALA. The authors conclude that BF‐200 ALA is more effective and provides slightly better value for money than MAL in DL‐PDT for mild and moderate AKs.
Early-onset airway damage in early-career elite athletes: A risk factor for exercise-induced bronchoconstriction
Authors: Anne-Charlotte Jonckheere, Sven Seys, Ellen Dilissen, An-Sofie Schelpe, Sarah Van der Eycken, Steffie Corthout, Tulasi Verhalle, Janne Goossens, Vincent Vanbelle, Sven Aertgeerts, Thierry Troosters, Koen Peers, Lieven Dupont, Dominique Bullens
Journal: Journal of Allergy and Clinical Immunology (2019)
Antitumor effects of zoledronic acid in combination with histone deacetylase inhibitor valproic acid.
Authors: Arne Strauß, Hagen Loertzer, Rolf-Hermann Ringert, Paul Thelen
Journal: Journal of Clinical Oncology (2012)

e15158 Background: The established utilisation of bisphosphonates is the treatment of metastatic bone disease derived from several tumor types including prostate (PCa) and breast cancer. However, recently preclinical as well as clinical evidence support anti-tumor activities of these drugs in their own right. To probe into the molecular basis of such observations we treated PCa bone metastasis derived cell lines (VCaP, PC-3) and breast cancer cells (MCF-7) with zoledronic acid (ZA) and ZA in combination with valproic acid (VPA). HDAC-Inhibitor VPA according to our previous findings rectifies aberrant androgen receptor signalling and thus, implies an anti-androgen element in these treatments. Methods: PCa cells (VCaP, PC-3) and breast cancer cells (MCF-7) were treated with ZA (Zometa, Novartis) at 0, 5, 25 or 100µM or same ZA concentrations in combination with VPA (5mM). Tumor cell viability and proliferation were analysed by AlamarBlue- and BrdU-tests. Gene expression and PSA secretion was quantitated by real time RT-PCR and was further assessed with ELISA-kits, respectively. Results: In all cell types ZA has no impact on tumor cell viability or proliferation of its own exceeding the effects of VPA alone. Likewise, PSA secretion in VCaP cells is not further diminished in the combined ZA/VPA treatments. However, among a marked impact on cancer relevant gene expression protective elements such as vitamin D- and β-estrogen-receptor are up-regulated by ZA alone and in excess by the combined treatment. Other genes associated with protective features such as IGFBP-3, SOCS-3 and Se-BP-3 are up-regulated only by the ZA/VPA combination. Conclusions: We present molecular evidence for anti-tumor effects of zoledronic acid. Our data suggest the necessity of a concomitant anti-androgen treatment for maximal benefit. The genes addressed by such treatments are more associated with cancer prevention than immediate androgen signalling targets. Therefore, the main anti-tumor potential of ZA may emerge from an early onset of combined therapies to prevent bone metastases.
The Russell viper venom time (RVVT) test for investigation of lupus anticoagulant (LA)
Authors: Emmanuel J. Favaloro
Journal: American Journal of Hematology (2019)

Abstract Lupus anticoagulants (LAs) are a laboratory representation of the clinical syndrome of antiphospholipid syndrome (APS), and can also arise in other pathological states. Laboratory testing for LA is complex and three separate recent guidelines have been published. One test, the Russell viper venom time (RVVT), is the mandated laboratory test for inclusion in LA identification/exclusion in all three guidance documents. This is because the the RVVT is recognized to have great sensitivity for LA, with this generally recognized to be greater than that of most other LA screening assays. However, the RVVT is also very sensitive to the presence of many anticoagulant drugs, which diminishes its specificity for LA. Various strategies can be used to improve LA specificity and reduce anticoagulant assay interference.
Association of Inflammation With Pronociceptive Brain Connections in Rheumatoid Arthritis Patients With Concomitant Fibromyalgia
Authors: Chelsea M. Kaplan, Andrew Schrepf, Eric Ichesco, Tony Larkin, Steven E. Harte, Richard E. Harris, Alison D. Murray, Gordon D. Waiter, Daniel J. Clauw, Neil Basu
Journal: Arthritis & Rheumatology (2019)

Objective Rheumatoid arthritis (RA) patients with concomitant fibromyalgia (FM) exhibit alterations in brain connectivity synonymous with central sensitization. This study was undertaken to investigate how peripheral inflammation, the principal nociceptive stimulus in RA, interacts with brain connectivity in RA patients with FM. Methods RA patients with concomitant FM and those without FM (FM+ and FM−, respectively; n = 27 per group) underwent functional connectivity magnetic resonance imaging. Seed‐to–whole‐brain functional connectivity analyses were conducted using seeds from the left mid/posterior insula and left inferior parietal lobule (IPL), which are regions that have been previously linked to FM symptoms and inflammation, respectively. The association between functional connectivity and erythrocyte sedimentation rate (ESR) was assessed in each group separately, followed by post hoc analyses to test for interaction effects. Cluster‐level, family‐wise error (FWE) rates were considered significant if the P value was less than 0.05. Results The group of RA patients with FM and those without FM did not differ by age, sex, or ESR ( P &gt; 0.2). In FM+ RA patients, increased functional connectivity of the insula–left IPL, left IPL–dorsal anterior cingulate, and left IPL–medial prefrontal cortex regions correlated with higher levels of ESR (all FWE‐corrected P &lt; 0.05). Post hoc interaction analyses largely confirmed the relationship between ESR and connectivity changes as FM scores increased. Conclusion We report the first neurobiologic evidence that FM in RA may be linked to peripheral inflammation via pronociceptive patterns of brain connectivity. In patients with such “bottom‐up” pain centralization, concomitant symptoms may partially respond to antiinflammatory treatments.
The diagnostic utility of targeted gene panel sequencing in discriminating etiologies of cytopenia
Authors: Gang Zheng, Ping Chen, Aparna Pallavajjalla, Lisa Haley, Lukasz Gondek, Amy Dezern, Hua Ling, Federico De Marchi, Ming‐Tseh Lin, Christopher Gocke
Journal: American Journal of Hematology (2019)

The diagnostic utility of somatic mutations in the context of cytopenias is unclear: clonal hematopoiesis can be found in healthy individuals, patients with aplastic anemia (AA), clonal cytopenia of undetermined significance (CCUS) and myelodysplastic syndrome (MDS). We examined a cohort of 207 well-characterized cytopenic patients with a 640-gene next generation sequencing (NGS) panel and compared its diagnostic utility with a "virtual" 41 gene panel. The TET2, SF3B1, ASXL1, and TP53 were the most commonly mutated genes (frequency > 10%). Mutations in the 640-gene panel show high sensitivity (98.3%) but low specificity (47.6%) for diagnosis of MDS. Notably, mutations of splicing factors and genes in the RAS pathway are relatively specific to MDS. Furthermore, high variant allele frequency (VAF) predicts MDS: when the VAF is set at 20%, the positive predictive value (PPV) for MDS is 95.9%, with a specificity of 95.3%. The presence of two or more somatic mutations with ≥10% VAF showed a PPV of 95.2%. While the "virtual" 41-gene panel showed a mild decrease in sensitivity (95.7% vs 98.3%), 100% specificity was observed when either VAF was set at ≥20% (100% vs 95.3%), or two or more somatic mutations had VAFs ≥ 10%. Our study shows targeted gene panel sequencing improves the diagnostic approach and accuracy for unexplained cytopenia, with its high sensitivity and high PPV for MDS when applying VAF cutoffs. Furthermore, a 41-gene panel was shown to have at least comparable performance characteristics to the large 640-gene panel.
CELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation
Authors: Fatemehsadat Esteghamat, James S. Broughton, Emily Smith, Rebecca Cardone, Tarun Tyagi, Mateus Guerra, András Szabó, Nelson Ugwu, Mitra V. Mani, Bani Azari, Gerald Kayingo, Sunny Chung, Mohsen Fathzadeh, Ephraim Weiss, Jeffrey Bender, Shrikant Mane, Richard P. Lifton, Adebowale Adeniran, Michael H. Nathanson, Fred S. Gorelick, John Hwa, Miklós Sahin-Tóth, Renata Belfort-DeAguiar, Richard G. Kibbey, Arya Mani
Journal: Nature Genetics (2019)
Eighty-two per cent of male professional football (soccer) players return to play at the previous level two seasons after Achilles tendon rupture treated with surgical repair
Authors: Alberto Grassi, Guendalina Rossi, Pieter D'Hooghe, Randeep Aujla, Massimiliano Mosca, Kristian Samuelsson, Stefano Zaffagnini
Journal: British Journal of Sports Medicine (2019)

Objective To evaluate the time to return to playing following acute Achilles tendon rupture (ATR) and surgical repair in professional male football (soccer) players. Methods Professional male football (soccer) players who sustained an ATR and underwent surgical repair were identified through internet-based injury reports from January 2008 to August 2018. Only League 1 and 2 players with injuries who had at least 1 year of follow-up from the search date were included. Injury history and time to return to play were retrieved from the public platform transfermarkt.com . For athletes who competed for at least two seasons after returning to play, re-ruptures and number of matches played were reported. Results 118 athletes (mean age 27.2±7.2 years) were included. 113 (96%) returned to unrestricted practice after a mean of 199±53 days, with faster recovery in players involved in national teams. Return to competition was after a mean of 274±114 days. In the 76 athletes with at least two seasons of follow-up, 14 (18%) did not compete at the pre-injury level during the two seasons following the index injury. Six players (8%) sustained a re-rupture within the first two seasons after return to play; four re-ruptures were in footballers who returned to play &lt;180 days after injury. Age &gt;30 years and re-ruptures had higher odds ratios of not returning to the same level of play. Conclusions 96% of professional male football players who underwent surgery to repair an ATR returned to unrestricted practice and then competition after an average time of 7 and 9 months, respectively. However, 18% did not return to the same level of play within the two seasons following their return, with a higher risk in those experiencing a re-rupture.
Abstract 17335: Inter Atrial Conduction Block Assessed by P Wave Morphology as Predictor of Clinical Atrial Fibrillation. A Meta-Analysis
Authors: Jorge Romero, Juan C Diaz, Ricardo Avendano, David F Briceno, Saurabh Kumar, Gregory F Michaud, Soo Kim, Andrea Natale, Luigi Di Biase, William G Stevenson
Journal: Circulation (2017)

Background: Interatrial conduction block (IACB) is mainly considered to be an electric abnormality of the Bachmann bundle that delays activation of the left atrium. IACB is manifest on a surface el...
PR interval prolongation, still a marker of worse outcome in patients treated cardiac resynchronization therapy patients
Authors: A. M. W. Antonius Martinus Wilhelmus Van Stipdonk, M. Dural, F. Salden, I. A. H. Ter Horst, H. J. G. M. Crijns, F. W. Prinzen, M. Meine, A. H. Maass, K. Vernooy
Journal: European Journal of Heart Failure (2019)
Higher incidence and mortality rates of cervical cancer in African-American women in Louisiana.
Authors: Genevieve Folse Maronge, Xiao-cheng Wu, Vivien Chen, Xiangrong Li, Brian C. Boulmay, Michelle Marie Loch
Journal: Journal of Clinical Oncology (2013)

e17522 Background: Cervical cancer [CC] incidence in the United States has decreased over the last thirty years in black and white Americans, however it is recognized that black women [BW] have higher incidence and mortality rates than white women [WW]. We evaluated race-specific incidence of CC, mortality rates of CC, and HPV vaccine usage rates in Louisiana [LA] during the last decade, the state with the second highest proportion of black Americans in the United States [US]. Methods: Data from Surveillance, Epidemiology, and End Results (SEER) registries were analyzed for trends in incidence and mortality rate [MR] in BW and WW in LA and the US. SEER 13 and SEER 18 data were used and standardized to the 2000 US population to estimate annual age-adjusted incidence and mortality rates. Results: The incidence of CC in WW in LA was 8.2 per 100,000 from 2006 to 2009, and 7.9 per 100,000 in WW in US. The incidence in BW in LA was 13.3 per 100,000, as compared to the US at 9.7 per 100,000, a 36% higher incidence in BW. The MR in WW in LA and the US was 2.4 and 2.2 per 100,000. The MR for BW in LA was 5.8 per 100,000 and the US was 4.3 per 100,000, a 37% higher incidence in BW. WW in LA and the US showed a peak in incidence between the ages of 35 and 45 from 2006 to 2009. The incidence in BW in LA peaked at 37.1 per 100,000 at age 85 and the incidence in BW in the US peaked at 25.6 per 100,000 at age 85. HPV vaccination rates for LA females ages 13-15 in 2008 and 2009 were 16.1% and 35.4%. Conclusions: BW in LA were twice as likely to be diagnosed with CC than WW with a higher MR. Though the incidence rate of CC is decreasing in WW and BW in the US and in WW in LA, it is increasing in BW in LA and continues to trend up throughout life in BW compared to WW. The high incidence of CC in BW in LA highlights the need to improve utilization of the HPV vaccine. A screening and treatment program targeting CC was implemented within the last decade in the LA public hospital system with the goal of reducing CC incidence and mortality.
Differences in 30-day preventable readmission rates after index cancer surgery in New York State hospitals.
Authors: Umut Sarpel, Natalia Egorova, Eugene Sosunov, Rebeca Franco, Yohana Taveras, Nina A. Bickell
Journal: Journal of Clinical Oncology (2013)

6640 Background: 30-day readmission rates are currently being used as a measure of performance quality. Among surgical patients, readmissions may be reducible for certain complications such as deep venous thrombosis or wound infection. We report 30-day readmission rates for potentially preventable readmissions following surgical treatment of the most common malignancies in the US. Methods: The most common cancer hospitalizations were identified from the Healthcare Cost and Utilization Project. Previously reported ICD-9 codes of preventable readmissions from cancer surgery were used to assess 30-day readmissions in New York State in 2009. We measured comorbidity using CMS hierarchical condition categories. Hospital teaching status was based on the American Hospital Association designation. Random effect hierarchical logistic regression models were run to account for clustering within hospitals. Results: 21,945 index admissions for cancer surgery occurred in 2009 at 169 teaching and 73 non-teaching hospitals. The most common operations were for prostate, breast, colon, lung, and renal cancer. 51% of patients were male and 12% were black. The overall readmission rate was 9.3% with readmissions being higher in non-teaching hospitals (11.2%) vs. teaching hospitals (8.6%) (p&lt;0.0001). There was a significant interaction between hospital teaching status and patient race. In teaching hospitals, there was no racial difference in readmission. However, in non-teaching hospitals, black patients were more likely to be readmitted (15.1% vs 10.9%; p=0.02). Multivariate models found that being male (OR=1.17; 95% CI: 1.04; 1.31; p=0.007), undergoing surgery at a non-teaching hospital (OR=1.16; 95% CI: 1.00; 1.35; p=0.048), black race (OR=1.47; 95% CI: 1.04; 2.08; p=0.029), and certain comorbidities increased a patient’s risk of 30-day readmission for a preventable cause. Conclusions: The 30-day preventable readmission rate after index hospitalizations for cancer surgery is higher in non-teaching hospitals, and this difference is more pronounced for black patients. Clinical protocols in teaching hospitals may play a role in this phenomenon. Efforts to address remediable causes of this disparity are warranted.
Lymphopenia combined with low TCR diversity to predict overall survival in metastatic breast cancer patients.
Authors: Manuarii Manuel, Olivier Tredan, Thomas Bachelot, Gilles Clapisson, Anais Courtier, Gilles Parmentier, Audrey Grives, Solene Perez, Jean-Francois Mouret, David Perol, Sylvie Chabaud, Isabelle Ray-Coquard, Sana Intidhar Labidi-Galy, Pierre Heudel, Jean-Yves Pierga, Christophe Caux, Jean-Yves Blay, Nicolas Pasqual, Christine Menetrier-Caux
Journal: Journal of Clinical Oncology (2012)

10562 Background: Lymphopenia (&lt;1 Giga/L) before initiation of chemotherapy is a predictive factor for toxicity and death in metastatic phase for cancer patients. Combinatorial diversity of T Cell Receptor beta chain (TCR-ß), as a measure of T cell repertoire diversity, was investigated and tested either alone or in combination with lymphopenia as a prognostic factor for overall survival (OS) in first line treatment of metastatic breast cancer (MBC) patients. Methods: Using semi quantitative multiplex PCR, the V-D-J combinatorial diversity of the TCR was measured on cryo-preserved blood samples from 2 cohorts of MBC patients before the initiation of the first line chemotherapy: in an experimental cohort (cohort A, n=66) and in a validation series (cohort B, n=67). A prognostic score, defined NDL (Number &amp; Diversity of Lymphocytes) combining lymphocyte count and TCR diversity was delineated. Univariate and multivariate analysis of prognostic factors for OS were performed in both cohorts. Results: Lymphopenia (&lt;1 Giga/L) was associated with shorter OS for cohort B while TCR diversity ≤33% (called divpenia) was associated with a reduced OS in cohort A. The combination of lymphopenia with low TCR diversity (called lympho-divpenia) was associated with poor OS compared to patients with either lymphocyte count ≥1 Giga/L or diversity &gt;33% or both, in cohort A (median OS: 7.6 vs 24.5 months, p.value =0.0006) and cohort B (median OS 10.6 vs 22.9 months, p.value =0.0035). In a multivariate analysis, including all significant clinical factors from the univariate analysis (PS, liver metastasis, hemoglobin) lympho-divpenia was found to be an independent prognostic factor in the pooled cohort (A+B) (p=0.005) along with triple negative tumors (p=0.011) and hemoglobin level (11.5 g/dL) (p=0.009). Conclusions: NDL score combining lymphopenia and reduced TCR diversity seems to be a strong prognostic factor for OS and could be use to improve care quality of MBC patients.
GMC fought to erase Bawa-Garba to uphold profession’s reputation
Authors: Clare Dyer
Journal: BMJ (2019)

The decision by the General Medical Council (GMC) to ask the High Court to strike off Hadiza Bawa-Garba from the medical register was taken to uphold the reputation of the profession, the regulator states in documents that the Information Commissioner’s Office ordered it to disclose.1

The GMC argued that the legal advice and other documents regarding the appeal were protected by legal privilege, but the commissioner concluded that they should be made public in response to a Freedom of Information Act request because of exceptional public interest in the case.

Bawa-Garba, a trainee paediatrician, was found guilty of gross negligence manslaughter over the death …