tbuckley/cabot-search huggingface dataset:
Patterns of systemic and local inflammation in patients with asthma hospitalised with influenza
Authors: Akhilesh Jha, Jake Dunning, Tanushree Tunstall, Ryan S. Thwaites, Long T. Hoang, Onn Min Kon, Maria C. Zambon, Trevor T. Hansel, Peter J. Openshaw
Journal: European Respiratory Journal (2019)

Background Patients with asthma are at risk of hospitalisation with influenza, but the reasons for this predisposition are unknown. Study setting A prospective observational study of adults with PCR-confirmed influenza in 11 UK hospitals, measuring nasal, nasopharyngeal and systemic immune mediators and whole-blood gene expression. Results Of 133 admissions, 40 (30%) had previous asthma; these were more often female (70% versus 38.7%, OR 3.69, 95% CI 1.67–8.18; p=0.0012), required less mechanical ventilation (15% versus 37.6%, Chi-squared 6.78; p=0.0338) and had shorter hospital stays (mean 8.3 versus 15.3 days, p=0.0333) than those without. In patients without asthma, severe outcomes were more frequent in those given corticosteroids (OR 2.63, 95% CI 1.02–6.96; p=0.0466) or presenting &gt;4 days after disease onset (OR 5.49, 95% CI 2.28–14.03; p=0.0002). Influenza vaccination in at-risk groups (including asthma) were lower than intended by national policy and the early use of antiviral medications were less than optimal. Mucosal immune responses were equivalent between groups. Those with asthma had higher serum interferon (IFN)-α, but lower serum tumour necrosis factor, interleukin (IL)-5, IL-6, CXCL8, CXCL9, IL-10, IL-17 and CCL2 levels (all p&lt;0.05); both groups had similar serum IL-13, total IgE, periostin and blood eosinophil gene expression levels. Asthma diagnosis was unrelated to viral load, IFN-α, IFN-γ, IL-5 or IL-13 levels. Conclusions Asthma is common in those hospitalised with influenza, but may not represent classical type 2-driven disease. Those admitted with influenza tend to be female with mild serum inflammatory responses, increased serum IFN-α levels and good clinical outcomes.
DNA damage response pathway alterations and clinical outcome in leiomyosarcoma.
Authors: Evan Rosenbaum, Philip Jonsson, Kenneth Seier, Ping Chi, Mark Andrew Dickson, Mrinal M. Gounder, Ciara Marie Kelly, Mary Louise Keohan, Li-Xuan Qin, Martee Leigh Hensley, Sandra P. D'Angelo, William D. Tap
Journal: Journal of Clinical Oncology (2019)

11048 Background: Leiomyosarcoma (LMS) is a complex karyotype sarcoma with frequent alterations in the homologous recombination (HR) pathway. Genomically unstable tumors with DNA damage repair (DDR) deficiencies may have improved responses to DNA damaging therapies, such as cytotoxic chemotherapy or PARP inhibitors. Methods: We retrospectively reviewed LMS patients treated at MSKCC who had targeted somatic DNA sequencing (MSK-IMPACT) performed on tumor tissue. 33 DDR genes, including 16 HR genes, were analyzed for oncogenic alterations. A composite HR deficiency (HRD) score measured tumor genomic scarring for each patient. To determine if DDR alteration status is prognostic of outcome, we analyzed the recurrence-free survival (RFS) of patients who underwent complete resection, and the overall survival (OS) of the whole cohort. Results: 211 patients had IMPACT testing between March 2014 and October 2018; 48% of samples were primary tumors and 52% recurrent/metastatic sites. Among soft tissue LMS (stLMS), there were 35 men and 55 women. 20% of patients had an oncogenic DDR gene alteration, 72% of which were in the HR pathway (table below). Uterine LMS (uLMS) had more DDR alterations than stLMS, though not statistically significant (p = 0.084). BRCA2 (n = 14 cases), RAD51B (8), and ERCC5 (4) were most frequently altered. HRD score significantly correlated with HRD alteration status (p = 0.004). DDR or HRD altered status and HRD score were associated with shorter RFS in patients with resectable disease, independent of age (p &lt; 0.05). Median OS for the cohort was 75 months (95% CI: 64 – 84). Men with stLMS had shorter OS compared to women (p = 0.025). OS did not significantly differ based on DDR or HRD status (p &gt; 0.05). Conclusions: One-fifth of LMS patients have one or more oncogenic somatic alterations in the DDR pathway, predominantly in effectors of HR. DDR status may be prognostic of recurrence risk. Further analyses to determine the association between DDR status and response to cytotoxic chemotherapy are ongoing. [Table: see text]
Low‐fluence fractional CO <sub>2</sub> laser in the treatment of idiopathic guttate hypomelanosis: a pilot study
Authors: S.H. Eun, H.S. Kwon, H.J. Ju, H.M. Jung, J.H. Lee, S.H. Oh, G.M. Kim, J.M. Bae
Journal: British Journal of Dermatology (2019)
The morbidity of cytoreduction/hyperthermic intraperitoneal chemoperfusion (HIPEC) in the modern era.
Authors: Michelle Haslinger, John Michael Kane, Valerie Francescutti, Rachel Burke, Jospeh J. Skitzki
Journal: Journal of Clinical Oncology (2012)

e14172 Background: Critics of cytoreduction/HIPEC for treatment of peritoneal surface malignancies cite high morbidity/mortality in historical published literature. With improved patient selection algorithms based upon recent clinical experience, perioperative morbidity/mortality should be comparable to the treatment of other GI malignancies. Methods: Retrospective data collection on all patients undergoing cytoreduction/HIPEC at a single institution (2 surgeons) from 2003-2011. Patient demographics, perioperative complications, mortality, and survival were analyzed (logistic regression modeling, Kaplan Meier, and Log rank testing). Results: 113 patients (45M/68F; median age 53 years) underwent 124 cytoreduction/HIPEC procedures. Primary tumor histology was colorectal adenocarcinoma (34%), appendiceal DPAM (24%), appendical adenocarcinoma (21%), mesothelioma (10%), and other (11%). 46% of patients received systemic chemotherapy prior to cytoreduction/HIPEC. Median HIPEC time was 12 hours (range 6 to 20 hours). All patients received mitomycin C at first HIPEC with 26% receiving a dose reduction. Median number of GI anastomoses was 1 (range 0-3). Median ICU stay was 1 day (range 0-21) and median length of stay (LOS) was 12 days (range 6-122). Major postoperative complications included wound infection (15%), anastomotic leak (11%), neutropenia (7%), pulmonary (5%), and thromboembolic events (2%). The reoperation rate for complications was 15%. Operative mortality at 30 and 60 days was 0% and 3%, respectively. As a surrogate for complications, LOS &gt;14 days occurred in 24% of patients. Median follow-up was 25 months (1-80 months). Median progression-free and overall survival were 26.3 and 68.5 months, respectively. An anastomotic leak was associated with increased LOS, decreased progression-free survival (15.3 months, p&lt; 0.05) and overall survival (15.3 months, p&lt; 0.005). Conclusions: Despite being stage IV disease, perioperative morbidity/mortality for cytoreduction/HIPEC is comparable to surgical treatment of primary upper GI malignancies. Patient selection and meticulous technique may be critical to avoid anastomotic leaks associated with decreased survival.
Changes to NHS health checks must be evidence based and beneficial, say GPs
Authors: Elisabeth Mahase
Journal: BMJ (2019)

A review of NHS health checks—which will look at tailoring checks based on risk and increasing the range of checks offered—must involve a “rigorous evaluation” to ensure they are safe, accurate, and of benefit to patients, GPs have warned.

The Department of Health and Social Care announced the review in the prevention green paper last month,1 and has now fleshed out its scope.

It says it will consider including additional checks to prevent musculoskeletal problems and hearing loss, as well as how the checks can be digitised and tailored so people are offered “personalised interventions” based on risk, location, predisposition to diseases, and their DNA.

While some experts welcomed the more targeted approach, others said the current scheme still needs to be evaluated for cost effectiveness and questioned how GPs will take on the extra work.

Health checks are currently offered to everyone aged …
Trichosanthes kirilowii tuber extract induce cell cycle arrest in Hep G2 cells at G2/M phase through inhibition of tubulin polymerization
Authors: Jang Woo Shin, Se Mi Oh, Jin Young Son, Jong Koo Kang, Chong Kwan Cho, Chang Gue Son
Journal: Cancer Research (2007)

4363  Plants have been a good source of effective anti-cancer agents. Plant-derived compounds have been used clinically as useful anti-cancer agents such as vinblastine, vincristine, the camptothecin derivatives, topotecan and irinotecan, etoposide, derived from epipodophyllotoxin, and paclitaxel and are over 60% of currently used anti-cancer agents. Trichosanthes kirilowii tuber has been used in traditional medicine in east Asia as an avortifacient and anti-diabetes. Trichosanthin (TCS) isolated from the roots is well known as a type 1 ribosome inactivating protein (RIPs) and induced an abortion in the second trimester of pregnancy. Anti-tumor effects of RIPs of Trichosanthes kirilowii such as TCS and trichomislin were reported, however the potency was weaky. To investigate anti-tumor activivites of extract of Trichosanthes kirilowii tuber with 50% MeOH (TKE) , we tested cytotoxicity of TKE using CCK-8 (WST-8). TKE inhibited growth of Hep G2 cells in a dose dependent manner and the cells treated with TKE were shrunk under microscopy. So we also determined released LDH to know that TKE kill Hep G2 cells. LDH release was not observed for 48 h treatment. Above the results, we thought TKE inhibit cell growth through not kill but cell cycle arrest. In FACS analysis of cells treated with TKE, G2/M phase arrest was observed. We thought that cell cycle arrest by TKE was associated with tubulin polymerization like paclitaxel or colchicine. We observed intracellular tubulin by immunofluorescence and we knew that cell shrinkage due to tubulin change. Although this change looks like decrease of microtubulin, we performed in vivo polymerization assay to clear effect of TKE on tubulin polymerization. We confirmed that TKE inhibit polymerization of tubulin. In real-time PCR, we knew beta tubulin mRNA did’t affect by TKE treatemt, whereas alpha-tubulin mRNA expression was up-regulated in a time dependant manner. On the other hand, we verified that protein content of TKE is 0.58% and TKE don’t contain TCS using protein analysis. Therefore, anti-tubulin polymerization effect of TKE is not associated with TCS. In the event, TKE arrest cell cycle through inhibition of tubulin polymerization. These results suggest that Trichosanthes kirilowii would be a potent anti-tumor agent.
Exacerbation action plans for patients with COPD and comorbidities: a randomised controlled trial
Authors: Anke Lenferink, Job van der Palen, Paul D.L.P.M. van der Valk, Paul Cafarella, Anneke van Veen, Stephen Quinn, Catharina G.M. Groothuis-Oudshoorn, Morton G. Burt, Mary Young, Peter A. Frith, Tanja W. Effing
Journal: European Respiratory Journal (2019)

This international randomised controlled trial evaluated whether COPD patients with comorbidities, trained in using patient-tailored multidisease exacerbation action plans, had fewer COPD exacerbation days than usual care (UC). COPD patients (Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification II–IV) with ≥1 comorbidity (ischaemic heart disease, heart failure, diabetes, anxiety, depression) were randomised to a patient-tailored self-management intervention (n=102) or UC (n=99). Daily symptom diaries were completed for 12 months. The primary outcome “COPD exacerbation days per patient per year” was assessed using intention-to-treat analyses. No significant difference was observed in the number of COPD exacerbation days per patient per year (self-management: median 9.6 (interquartile range (IQR) 0.7–31.1); UC: median 15.6 (IQR 3.0–40.3); incidence rate ratio (IRR) 0.87 (95% CI 0.54; 1.39); p=0.546). There was a significantly shorter duration per COPD exacerbation for self-management (self-management: median 8.1 (IQR 4.8–10.1) days; UC: median 9.5 (IQR 7.0–15.1) days; p=0.021), with no between-group differences in the total number of respiratory hospitalisations (IRR 0.76 (95% CI 0.42; 1.35); p=0.348), but a lower probability of ≥1 for respiratory-related hospitalisation compared to UC (relative risk 0.55 (95% CI 0.35; 0.87); p=0.008). No between-group differences were observed in all-cause hospitalisations (IRR 1.07 (95% CI 0.66; 1.72)) or mortality (self-management: n=4 (3.9%); UC: n=7 (7.1%); relative risk 0.55 (95% CI 0.17; 1.84)). Patient-tailored exacerbation action plans for COPD patients with comorbidities did not significantly reduce exacerbation days, but reduced the duration per COPD exacerbation and the risk of having at least one respiratory-related hospitalisation during follow-up, without excess all-cause mortality.
Coronary Access After Repeated Transcatheter Aortic Valve Implantation
Authors: Nicola Buzzatti, Vittorio Romano, Ole De Backer, Lars Soendergaard, Liesbeth Rosseel, Pal Maurovich-Horvat, Julia Karady, Bela Merkely, Stefania Ruggeri, Bernard Prendergast, Michele De Bonis, Antonio Colombo, Matteo Montorfano, Azeem Latib
Journal: JACC. Cardiovascular imaging (2019)
Effect of Erlotinib Plus Bevacizumab vs Erlotinib Alone on Progression-Free Survival in Patients With Advanced<i>EGFR</i>-Mutant Non–Small Cell Lung Cancer
Authors: Thomas E. Stinchcombe, Pasi A. Jänne, Xiaofei Wang, Erin M. Bertino, Jared Weiss, Lyudmila Bazhenova, Lin Gu, Christie Lau, Cloud Paweletz, Anthony Jaslowski, Gregory J. Gerstner, Maria Q. Baggstrom, Stephen Graziano, James Bearden, Everett E. Vokes
Journal: JAMA Oncology (2019)

Erlotinib is a standard first-line therapy for patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Median progression-free survival (PFS) with erlotinib is approximately 10 months.To determine whether adding bevacizumab to erlotinib treatment results in superior progression-free survival compared with erlotinib alone.This phase 2 randomized clinical trial compared erlotinib plus bevacizumab with erlotinib alone in EGFR-mutant NSCLC. The trial was conducted in 17 US academic and community medical centers among 88 patients with EGFR exon 19 deletion or exon 21 L858R mutation based on local testing and stage 4 NSCLC who were eligible for bevacizumab. Patients were enrolled between November 2, 2012, and August 22, 2016, and followed up for a median (range) of 33 (0.7-62.5) months. Data were analyzed on August 28, 2018, and included data from November 2, 2012, to August 20, 2018.Patients were randomized with equal allocation to 150 mg of oral erlotinib daily alone or with 15 mg/kg of intravenous bevacizumab every 3 weeks. Study therapy continued until disease progression, unacceptable adverse event, or withdrawal of consent.The primary outcome was PFS as assessed by the investigator; secondary outcomes were objective response rate (ORR), adverse events, and overall survival (OS). Analysis was designed to detect a hazard ratio (HR) of 0.667 for PFS (an improvement from a median PFS of 10 to 15 months).Among 88 patients enrolled, the median (range) age was 63 (31-84) years; 62 patients (70%) were female; 75 (85%) were white, 8 (9%) were African American, 3 (3%) were Asian, and for 2 (2%), data on race were not available. Forty-eight patients (55%) were never smokers, 45 patients (51%) were of Eastern Cooperative Oncology Group performance status 1, and 59 patients (67%) had EGFR exon 19 deletion. Compared with erlotinib, the combination did not result in a significant difference in PFS (HR, 0.81; 95% CI, 0.50-1.31; P = .39; median PFS 17.9 [combination] and 13.5 months [erlotinib]), ORR (81% vs 83%; P = .81), and OS (HR, 1.41; 95% CI, 0.71-2.81; P = .33; median OS, 32.4 months [combination] and 50.6 months [erlotinib]). Adverse events of grade 3 or higher observed in 5 or more patients in the combination and erlotinib arms were skin eruption in 11 (26%) vs 7 (16%) patients, diarrhea in 4 (9%) vs 6 (13%) patients, hypertension in 17 (40%) vs 9 (20%) patients, and proteinuria in 5 (12%) vs 0 (0%) patients.Erlotinib plus bevacizumab compared with erlotinib did not result in a significant improvement in PFS in EGFR-mutant NSCLC.ClinicalTrials.gov identifier: NCT01532089.
Acyl-CoA-Binding Protein Is a Lipogenic Factor that Triggers Food Intake and Obesity
Authors: José M. Bravo-San Pedro, Valentina Sica, Isabelle Martins, Jonathan Pol, Friedemann Loos, Maria Chiara Maiuri, Sylvère Durand, Noélie Bossut, Fanny Aprahamian, Gerasimos Anagnostopoulos, Mireia Niso-Santano, Fernando Aranda, Ignacio Ramírez-Pardo, Justine Lallement, Jessica Denom, Erwan Boedec, Philip Gorwood, Nicolas Ramoz, Karine Clément, Veronique Pelloux, Alili Rohia, François Pattou, Violeta Raverdy, Robert Caiazzo, Raphaël G.P. Denis, Patricia Boya, Lorenzo Galluzzi, Frank Madeo, Stéphanie Migrenne-Li, Céline Cruciani-Guglielmacci, Nektarios Tavernarakis, Carlos López-Otín, Christophe Magnan, Guido Kroemer
Journal: Cell Metabolism (2019)
Incidence and significance of K-RAS mutation in first line treatment of colorectal cancer (cc): Experience of a single institution (Hospital Universitario Central de Asturias (HUCA))
Authors: J. Vieitez, P. Jiménez Fonseca, M. Fernandez de Sanmamed, A. S. Pitiot, G. Crespo, J. Berros, C. Muriel, M. Izquierdo, P. Pardo, A. Lacave
Journal: Journal of Clinical Oncology (2009)

e15081 Background: Although the significance of K-RAS mutation and cetuximab/panitumumab has been established in first line (ASCO 08 abstract 2# and 4000#) and in previously treated patients (pts) (NEJM 2008; 359: 1757. JCO 2008; 26: 374. JCO 2008; 26: 1626), data of the significance of this mutation in relation to bevacizumab is scarcer (JNCI 2005; 97: 981). Methods: Sample tissue of alive patients diagnosed of stage IV colorectal cancer were analyzed for the presence of K-RAS mutation by PCR amplification and direct sequencing. Data regarding presence of K-RAS mutation were retrospectively analyzed in relation to clinical data. Results: From IV to XII 08 122 paraffin embedded samples were analyzed. The percentage of mutant cases were 41% (95% CI 32–51%). The most frequent mutant type was Gly12Asp (37%) followed by Gly12Val (25%) and Gly13Asp (19%). We have clinical data of 94 pts. 62 were men and 32 female. 25 pts had received previous complementary treatment; in 80 pts primary tumor was previously resected (85%); median number of affected organs was 1 (1–4); in first line 76 pts received bevacizumab and 18 did not received any biological agent. Response Rate (RR) between mutant and no mutant pts was 48% (95% CI 37–59%) vs 47.8% (95% CI 32–63%) (p=0.92). Median follow up was 15.4 months. Progression free survival was 15 months for mutant and native K-RAS. There were no differences in response or PFS in any subgroup studied. Multivariable Cox analysis did not find any significant difference between sex (p=0.78), primary resected organ (p=0.28), liver metastases (p=0.37), LDH value at diagnosis (p=0.0.43), employ of biological agents in first line (p=0.37) or mutation in K-RAS gene (p=0.68). Conclusions: The percentage of K-RAS mutants is coherent with the results of the literature; mutations Gly12Asp, Gly12Val, and Gly13Asp represents the majority of the cases (81%); no significant relation was found between responses or DFS and mutations in the gene. No significant financial relationships to disclose.
Integrated clinical, histopathological, and molecular data analysis of 190 central nervous system germ cell tumors from the iGCT Consortium
Authors: Hirokazu Takami, Kohei Fukuoka, Shintaro Fukushima, Taishi Nakamura, Akitake Mukasa, Nobuhito Saito, Takaaki Yanagisawa, Hideo Nakamura, Kazuhiko Sugiyama, Masayuki Kanamori, Teiji Tominaga, Taketoshi Maehara, Mitsutoshi Nakada, Yonehiro Kanemura, Akio Asai, Hideo Takeshima, Yuichi Hirose, Toshihiko Iuchi, Motoo Nagane, Koji Yoshimoto, Akira Matsumura, Kazuhiko Kurozumi, Hiroyuki Nakase, Keiichi Sakai, Tsutomu Tokuyama, Soichiro Shibui, Yoichi Nakazato, Yoshitaka Narita, Ryo Nishikawa, Masao Matsutani, Koichi Ichimura
Journal: Neuro-Oncology (2019)

We integrated clinical, histopathological, and molecular data of central nervous system germ cell tumors to provide insights into their management.Data from the Intracranial Germ Cell Tumor Genome Analysis (iGCT) Consortium were reviewed. A total of 190 cases were classified as primary germ cell tumors (GCTs) based on central pathological reviews.All but one of the cases that were bifocal (neurohypophysis and pineal glands) and cases with multiple lesions including neurohypophysis or pineal gland were germinomas (34 of 35). Age was significantly higher in patients with germinoma than other histologies. Comparison between tumor marker and histopathological diagnoses showed that 18.2% of histopathologically diagnosed germinomas were marker positive and 6.1% of non-germinomatous GCTs were marker negative, suggesting a limitation in the utility of markers or histopathology alone using small specimens for diagnosis. Comparison between local and central histopathological diagnoses revealed a discordance of 12.7%. Discordance was significantly less frequent in biopsy cases, implying difficulty in detecting all histopathological components of heterogeneous GCTs. Germinomas at the typical sites (neurohypophysis or pineal gland) showed a better progression-free survival than those at atypical sites (P = 0.03). A molecular clinical association study revealed frequent mitogen-activated protein kinase (MAPK) pathway mutations in males (51.4% vs 14.3%, P = 0.007), and phosphatidylinositol-3 kinase/mammalian target of rapamycin (PI3K/mTOR) pathway mutations in basal ganglia cases (P = 0.004). Basal ganglia cases also had frequent chromosomal losses. Some chromosomal aberrations (2q, 8q gain, 5q, 9p/q, 13q, 15q loss) showed potential prognostic significance.The in-depth findings of this study regarding clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.