tbuckley/cabot-search huggingface dataset:
Association of p53 mutations with progression-free survival (PFS) and overall survival (OS) in EGFR-mutated non-small cell lung cancer (NSCLC) patients (p) treated with erlotinib.
Authors: Amaya Gasco, Miguel Angel Molina-Vila, Jordi Bertran-Alamillo, Clara Mayo, Carlota Costa, Ana Gimenez Capitan, Bartomeu Massuti, Carlos Camps, Enric Carcereny Costa, Santiago Viteri Ramirez, Alejandro Martinez-Bueno, Susana Benlloch, Laia Capdevila, Sara Cros, Rut Porta, Felipe Cardenal, Joaquim Bosch, Jose Javier Sanchez, Miquel Taron, Rafael Rosell
Journal: Journal of Clinical Oncology (2012)

e18143 Background: Advanced NSCLC p with EGFR mutations have a median PFS of 14 months (m) and OS of 27 m when treated with erlotinib. In NSCLC cell lines, tyrosine kinase inhibitors (TKIs) induce p53 translocation from the cytoplasm to the nucleus and subsequent upregulation of Fas and caspase activation leading to apoptosis, but this mechanism was defective in p53-null cells. We tested whether TP53 mutations influence outcome to erlotinib in EGFR-mutated p. Expression levels of the p53 repressor MDM2 were also examined. Methods: We assessed p53 status in pretreatment paraffin-embedded tumor samples from 93 erlotinib-treated, EGFR-mutated advanced NSCLC p. Mutations in exons 5, 6, 7 and 8 were screened by High Resolution Melting analysis followed by sequencing of the amplified products with non-wild-type (wt) melt curves. All mutant samples were re-confirmed by standard PCR and sequencing. Expression levels of MDM2 mRNA were determined by quantitative RT-PCR. Results: Mutations in exons 5-8 of TP53 were detected in 26 of 93 p (28%). We found an unusually high frequency of in-frame and frameshift deletions (23% of mutations), indicating that the spectrum of p53 mutations might be different in EGFR-mutated NSCLC. Mutations were less frequent in p with ECOG PS &gt;2 and more frequent in p with the T790M mutation. OS was 15 m in the 16 p with missense mutations 31 m in p with wt p53 and not reached in p with non-missense mutations (P=0.04). PFS was 9 m for 14 p with mutations in one of the p53 DNA binding motifs (DBMs), compared to 19 m for wt p and 27 m for p with non-DBM mutations. MDM2 mRNA levels were significantly lower in tumors with p53 mutations, especially in DBM mutations. In the case of wt p, high MDM2 expression correlated with longer PFS and OS in p with wt p53. Conclusions: TP53 mutations co-exist with EGFR mutations in a significant number of p; missense mutations correlate with shorter OS and mutations in DBMs correlate with shorter PFS. This finding paves the way for the possibility of combining erlotinib with a drug restoring p53 function in those p harboring certain types of mutations in the TP53 gene.
Growing up on a farm may cut risk of allergic conditions in adulthood
Authors: Susan Mayor
Journal: BMJ (2016)

Growing up on a farm is associated with lower odds of allergic conditions in adulthood, including atopic asthma and rhinitis, than an inner city childhood, a European study has found.1

Evidence has shown that exposure to environmental or microbial biodiversity in early life may influence the subsequent risk of allergic conditions. To investigate this, researchers studied 10 201 people aged 26-54 from 14 countries taking …
Therapeutic Utility of PI3Kγ Inhibition in Leukemogenesis and Tumor Cell Survival
Authors: Thomas Diacovo, Dosh Whye, Evgeni Efimenko, Jianchung Chen, Valeria Tosello, Kim De Keersmaecker, Adam Kashishian, Mary Ann Thompson, Mireia Castillo, Carlos Cordon-Cardo, Utpal P. Dave, Adolfo A. Ferrando, Brian J. Lannutti, Prem Subramaniam
Journal: Blood (2012)
Salvage chemotherapy with CPT-11 for recurrent temolozomide-refractory anaplastic oligodendroglioma
Authors: M. C. Chamberlain
Journal: Journal of Clinical Oncology (2007)

12526 Background: There is no standard therapy for alkylator-resistant AO and hence a need exists for new therapies. Methods: Twenty patients (10 men; 10 women) ages 27–47 (median 38), with radiographically recurrent AO were treated. All patients had previously been treated with surgery, involved-field radiotherapy, and adjuvant chemotherapy (TMZ in 14; BCNU in 6). 13 patients were treated at first recurrence with an alternative chemotherapy (TMZ in 6 all previously treated with BCNU; 5 with PCV and 1 each with carboplatin, sorafenib, or cyclophosphamide). 11 patients underwent repeat surgery. All patients were treated at either first or second recurrence with CPT-11 administered intravenously once every 3 weeks (350mg/m 2 in patients on non-enzyme inducing anticonvulsants or no anticonvulsant; 600mg/m 2 in patients on enzyme inducing anticonvulsants), operationally defined as a single cycle. Neurological and neuroradiographic evaluations were performed every 8–9 weeks. Results: All patients were evaluable for toxicity and response. A total of 129 cycles of CPT-11 (median 4.5 cycles; range 3–18) was administered. CPT-11 related toxicity included diarrhea (4 patients; 2 [10%] grade 3), neutropenia (3; 3 [15%] grade 3), fatigue (3; 3 [15%] grade 3), and delayed nausea/vomiting (1; 1 [5%] grade 3). 5 patients (25%) demonstrated a partial radiographic response, 7 (35%) demonstrated stable disease and 8 (40%) had progressive disease following three cycles of CPT-11. Time to tumor progression ranged from 2 - 13.5 months (median: 4.5 months). Survival ranged from 3 - 21 months (median: 6 months). 6-month and 12-month PFS were 30% and 25% respectively. Conclusions: CPT-11 demonstrated modest efficacy with acceptable toxicity in this cohort of adult patients with recurrent AO all of whom had failed prior TMZ chemotherapy. No significant financial relationships to disclose.
Identification of a rabid dog in France illegally introduced from Morocco: comment
Authors: Lara Payne, Collective on behalf of the Preparedness and R
Journal: Eurosurveillance (2008)

As highlighted in the above article by a multidisciplinary investigation team from France, there have been previous reports of dogs being illegally introduced to France and subsequently identified with rabies infection. No human cases related to these events have been identified to date. Although exposure to rabies from animals in the European Union (EU) remains a rare event, in the absence of post-exposure prophylaxis before symptoms rabies is invariably a deadly infection in humans. The French authorities have implemented extensive measures, including the tracing of humans and animals possibly in contact with the suspected rabid dogs, and awareness of the event has been relayed to the general public through the media in order to assist in identifying other possible human or animal contacts.
Mental distress, chronic fatigue, and neuroticism as significant predictors of side effects in prostate cancer patients after radical prostatectomy (RP) or high-dose radiotherapy (RAD).
Authors: A. Stensvold, S. D. Fossa, A. A. Dahl, K. Axcrona, W. Lilleby, S. Smeland
Journal: Journal of Clinical Oncology (2010)

e15057 Background: Mental distress (MD) and chronic fatigue (CF) have been studied to some extent in prostate cancer patients (PCaPs), while that hardly is the case for the personality trait of neuroticism. We studied the above three factors as pre-treatment predictors of sexual, urinary and bowel bother in PCaPs 12 months after RP or RAD (>74Gy). Methods: The Extended UCLA Prostate Cancer Index form was completed pre-treatment and at 12 months post-treatment by patients treated with RP ( N:177) or RAD (N:116), none of them ever having radiotherapy or hormones after their local treatment. The primary outcome variables examined with logistic regression analyses was self-reported sexual, urinary, and bowel bothers at 12 month follow-up (present vs. absent). MD was defined as caseness by the Hospital Anxiety and Depression Scale, CF as caseness by the Fatigue Questionnaire, and neuroticism caseness by the Eysenck Personality Questionnaire. Other independent pre-treatment variables were demography, comorbidity, lifestyle and cancer-related parameters. Results: In univariate analyses within the combined RP/RAD group caseness of MD predicted both bowel (OR=4.66, p<0.001) and urinary bother (OR=5.04, p<0.001). Caseness of CF was associated with bowel (OR=12.40, p<0.001), sexual (OR=2.36, p=0.06) and urinary bother (OR=3.16, p=0.06). Caseness of neuroticism was associated with bowel (OR=6.53, p<0.001) and urinary bother (OR=3.58, p=0.007). In multivariate analyses, including treatment (RAD as reference), age, education, civil status, comorbidity and T-category, the associations between CF and bowel bother (OR=4.60, p=0.006) and neuroticism and bowel (OR=3.85, p=0.02) or urinary bother (OR=3.30, p=0.02) persisted. Further, compared to RAD significantly more patients reported sexual and urinary bother after RP, whereas the frequency of bowel bother was significantly decreased. Conclusions: Caseness of MD, CF and neuroticism significantly predicted side effects 12 months after curatively intended local treatment in PCaPs. Patient counselling before treatment should take these factors into account. No significant financial relationships to disclose.
Epidémie de gastro-entérite à salmonelle lors d’une soirée d’ouverture d’un restaurant en Grèce, juin 1998
Authors: C Hadjichristodoulou, E Nikolakopoulou, K Karabinis, E Karakou, A Markogiannakis, C Panoulis, M Lampiri, P Tassios
Journal: Eurosurveillance (1999)

Jusqu’a tres recemment en Grece, le systeme de declaration des maladies infectieuses a ete inadapte. En 1998, un nouveau systeme de declaration a ete mis en place impliquant une declaration hebdomadaire des laboratoires collaborateurs du pays – a l’aide de formulaires standard envoyes par e-mail ou par fax - et des rapports reguliers sur le nombre total de tests et de resultats positifs relatifs a certaines maladies transmissibles selectionnees. Alors qu’en 1997, seuls 326 cas d’infections a salmonelle avaient ete rapportes au Ministere de la Sante, 622 cas ont ete declares en 15 semaines en 1998 avec ce nouveau systeme.
Mutation analysis of the <i>BRCA1</i> and <i>BRCA2</i> genes in Turkish patients with breast cancer.
Authors: Angela Apessos, Nikolaos Tsoulos, Eirini Papadopoulou, Vasiliki Metaxa-Mariatou, Konstantinos Agiannitopoulos, Sualp Tansan, Ceyhun Irgil, Erhan Gokmen, Metin Cakmakci, Can Basaran, Ajlan Atasoy, Gul Basaran, George Nasioulas
Journal: Journal of Clinical Oncology (2015)

e12536 Background: Approximately 5-10% of breast cancer cases are hereditary. Germline mutations in the BRCA1 and BRCA2genes are responsible for 80% of inherited breast cancer cases. Carriers of such mutations are usually members of families with at least 1-2 cases of breast cancer diagnosed before the age of 40 years. Pathogenic mutations throughout the coding region of the two genes have been identified. Founder mutations have been identified in various populations. AIM: To date there have been limited data on the contribution of mutations in the BRCA1 and BRCA2genes in Turkish families with breast cancer. We aimed to identify mutations in high risk patients of this population, as judged by the age at diagnosis of breast cancer and the immunohistochemical characterisistcs of the patients’ tumours. Methods: In the past 2 years, 114 families have been analyzed by our group. Genomic DNA extracted from blood samples was subjected to PCR using the commercially available CE IVD BRCA MASTR Dx kit (MULTIPLICOM NV, J Mol Diag, 14:623-30, 2012) for the two genes. Sequencing was carried out using the Next Generation Sequencing platform MiSeq (Illumina). Large genomic rearrangements, in addition to the presence of the 1100delC mutation in the CHEK2 gene, were investigated by MLPA (BRCA1: P002, BRCA2, CHEK2:P045, MRC Holland; AJHG 67:841-50, 2000). Results: A pathogenic mutation has been identified in 16 (14%) of the 114 patients analyzed. Of the mutations identified, 7 were located in the BRCA1 gene and 9 in BRCA2. Of the mutations identified 5 (1 in BRCA1 and 4 in BRCA2) have not been previously described. Most interestingly, 7 of the mutations (4 in BRCA1 and 3 in BRCA2) were large genomic rearrangements, encompassing one or more exons of the gene. Finally, 15 variants which have not been previously described were identified. Conclusions: Our results indicate that in accordance to the frequency of mutations identified in other populations, pathogenic mutations in the BRCA1 and BRCA2 genes can be identified in 14% of high risk Turkish families. Of those, a striking 44% are large genomic rearrangements, indicating that analysis of these two genes in patients of Turkish origin must consist of a variety of methods, capable of detecting all types of mutations.
Role of FDG-PET/CT in the Staging of Patients with Follicular Lymphoma
Authors: Sayako Yuda, Dai Maruyama, Hiroaki Kurihara, Akiko Miyagi Maeshima, Kosuke Toyoda, Yamauchi Nobuhiko, Shin-ichi Makita, Suguru Fukuhara, Wataru Munakata, Yukio Kobayashi, Hirokazu Taniguchi, Kensei Tobinai
Journal: Blood (2015)
Case 30-2016
Authors: Kelly E. Irwin, Oliver Freudenreich, Jeffrey Peppercorn, Alphonse G. Taghian, Phoebe E. Freer, Thomas M. Gudewicz
Journal: New England Journal of Medicine (2016)

A 63-year-old woman with bipolar disorder and a history of cancer was admitted for electroconvulsive therapy. Chest CT revealed a new invasive breast cancer. The patient initially declined surgery and cancelled appointments. Management decisions were made.
Intracardiac Heart Rate Variability (HRV) of the Native Sinus Node (NS) in Heart Transplants. A New Method to Assess the Restoration of Autonomic Function After Cardiac Transplantation
Authors: D Ramaekers, André Aubert, F Beckers, Johan Van Cleemput, W Droogné, Johan Vanhaecke, Frans Van de Werf, Hugo Ector
Journal: Journal of the American College of Cardiology (1998)
Physiotherapy, and speech and language therapy intervention for patients with refractory chronic cough: a multicentre randomised control trial
Authors: Sarah A F Chamberlain Mitchell, Rachel Garrod, Lynne Clark, Abdel Douiri, Sean M Parker, Jenny Ellis, Stephen J Fowler, Siobhan Ludlow, James H Hull, Kian Fan Chung, Kai K Lee, H Bellas, Anand Pandyan, Surinder S Birring
Journal: Thorax (2016)

<h3>Background</h3> Physiotherapy, and speech and language therapy are emerging non-pharmacological treatments for refractory chronic cough. We aimed to investigate the efficacy of a physiotherapy, and speech and language therapy intervention (PSALTI) to improve health-related quality of life (HRQoL) and to reduce cough frequency in patients with refractory chronic cough. <h3>Methods</h3> In this multicentre randomised controlled trial, patients with refractory chronic cough were randomised to four weekly 1:1 sessions of either PSALTI consisting of education, laryngeal hygiene and hydration, cough suppression techniques, breathing exercises and psychoeducational counselling or control intervention consisting of healthy lifestyle advice. We assessed the change in HRQoL at week 4 with the Leicester Cough Questionnaire (LCQ). Secondary efficacy outcomes included 24-hour objective cough frequency (Leicester Cough Monitor) and cough reflex sensitivity. The primary analysis used an analysis of covariance adjusted for baseline measurements with the intention-to-treat population. This study was registered at UK Clinical Research Network (UKCRN ID 10678). <h3>Findings</h3> Between December 2011 and April 2014, we randomly assigned 75 participants who underwent baseline assessment (34 PSALTI and 41 controls). In the observed case analysis, HRQoL (LCQ) improved on average by 1.53 (95% CI 0.21 to 2.85) points more in PSALTI group than with control (p=0.024). Cough frequency decreased by 41% (95% CI 36% to 95%) in PSALTI group relative to control (p=0.030). The improvements within the PSALTI group were sustained up to 3 months. There was no significant difference between groups in the concentration of capsaicin causing five or more coughs. <h3>Interpretation</h3> Greater improvements in HRQoL and cough frequency were observed with PSALTI intervention. Our findings support the use of PSALTI for patients with refractory chronic cough. <h3>Trial registration number</h3> UKCRN ID 10678 and ISRCTN 73039760; Results.
Preclinical Validation of a Single-Treatment Infusion Modality That Can Eradicate Extremity Melanomas
Authors: Minhyung Kim, Nickolay Neznanov, Chandler D. Wilfong, Daria I. Fleyshman, Andrei A. Purmal, Gary Haderski, Patricia Stanhope-Baker, Catherine A. Burkhart, Katerina V. Gurova, Andrei V. Gudkov, Joseph J. Skitzki
Journal: Cancer Research (2016)

Abstract Isolated limb perfusion (ILP) with the chemotherapeutic agent melphalan is an effective treatment option for extremity in-transit melanoma but is toxic and technically challenging to deliver locoregionally. CBL0137 is an experimental clinical drug with broad anticancer activity in animal models, owing to its ability to bind DNA in a nongenotoxic manner and inactivate the FACT chromatin modulator essential for tumor cell viability. Here, we report that CBL0137 delivered by ILP in a murine melanoma model is as efficacious as melphalan, displaying antitumor activity at doses corresponding to only a fraction of the systemic MTD of CBL0137. The ability to bind DNA quickly combined with a favorable safety profile made it possible to substitute CBL0137 in the ILP protocol, using an intra-arterial infusion method, to safely achieve effective tumor suppression. Our findings of a preclinical proof of concept for CBL0137 and its administration via intra-arterial infusion as a superior treatment compared with melphalan ILP allows for locoregional treatment anywhere a catheter can be placed. Cancer Res; 76(22); 6620–30. ©2016 AACR.
Acute Graft Versus Host Disease (GVHD) Is Increased in Patients Receiving Cyclosporine/Cellcept as Frontline Prophylaxis Against GVHD in Pediatric Patients Undergoing Allogeneic Stem Cell Transplantation.
Authors: Sonali Lakshminarayanan, Paul Szabolcs, Vinod Prasad, Suhag Parikh, Susan Wood, Gilbert Ciocci, Lauren Stafford, Lynn Boyd, Timothy Driscoll, Paul L. Martin, Joanne Kurtzberg
Journal: Blood (2006)
P194 Inpatient adjustment of sub-optimal home mechanical ventilation (HMV) – an effective use of resources?: Abstract P194 Table 1
Authors: F Frost, B Al-Hakim, S Wordingham-Baker, V Ford, H Ashcroft, K Ward, R Parker, B Chakrabarti, R Angus, N Duffy
Journal: Thorax (2015)

<h3>Introduction</h3> HMV can be initiated and monitored as either inpatient or outpatient. There is little evidence for best practice in this field and inpatient ventilation beds are a scarce resource. We evaluated patients, with sub-optimal HMV, admitted to our tertiary unit for adjustments to consider whether these admissions were successful, and hence an effective use of resources. <h3>Methods</h3> Patients were identified from our ventilation unit’s database. Notes, oximetry and ventilator download from pre-admission, pre-discharge and post-discharge were retrospectively analysed. <h3>Results</h3> In a 6-month period (June–December 2013) 30 patients were admitted to our unit for adjustments of HMV. 43% were female. Obesity related sleep disorder formed the majority of underlying conditions (53%), with musculoskeletal deformities (20%) and neuromuscular conditions (10%) also frequently seen. Median length of stay was 2 days. HMV was discontinued during admission in 2 cases in line with patient wishes. 19 (63%) were deemed to have had successful admissions, defined as normalisation of at least one abnormal ventilation parameter (pCO<sub>2</sub> &gt;6.0, desaturations &gt;14/hr, time below 90% of &gt;30 min, mean saturations of &lt;88%, usage &gt;6 hrs, leak &lt;50 L/min). Of the 19 successful admissions, 6 showed sustained improvement post-discharge. 11 (37%) admissions were deemed unsuccessful, poor baseline usage and missed outpatient appointments were observed in this group. Noteworthy improvements were made to oximetry parameters during admission, although not all of these were maintained post-discharge (Table 1). Ventilator leak and usage information was available for 22 (73%) patients. Excess leak (50 &gt;L/min) was seen in 10 patients pre-admission, only 1 patient had excess leak post-discharge. Pre-admission usage of &lt;2 h/night was seen in 6 patients, only 1 showed sustained improvement in usage. 8 patients were admitted with usage of 2– 4 h, 4 improved post discharge usage to &gt;6 h and only 1 showed deterioration in usage. <h3>Conclusion</h3> Admitting patients for adjustments to HMV can improve ventilation parameters yet only some of these improvements are maintained after discharge. There appears to be a subset of patients who do not benefit from inpatient admissions, particularly patients with poor baseline usage. We suggest careful selection of patients to ensure effective use of limited resources.
BMA considers plans after suspending junior doctor strikes
Authors: Abi Rimmer
Journal: BMJ (2016)

The BMA is considering its plans for further action after announcing that three rounds of planned strikes by junior doctors in England have been suspended.

After a meeting of its Junior Doctors Committee on Saturday 24 September, the BMA announced that the planned series of five day strikes in October, November, and December would not go ahead.1 The association said that it was …
P0976 : Effect of rosuvastatin or/and β-carotene and dietary control on non-alcoholic fatty liver disease (NAFLD) in rats
Authors: O.A. Hammam, S.H. Seif el Din, N.M. El-Lakkany, A.A. El-Naggar, H.A. Abd El--Latif, A.A. Ain-Shoka, F.A. Ebeid
Journal: Journal of Hepatology (2015)
Bortezomib Added to the Standard Mobilization Regimen of G-CSF and High-Dose Cyclophosphamide Is a Safe and Effective Combination for a High Yield Stem Cell Collection While Promoting Further Tumor Mass Reduction in Myeloma.
Authors: Jessica L. Stern, Brian Di Carlo, Michael W. Schuster, Tsiporah B. Shore, John G. Harpel, Roger Pearse, Faiza Zafar, Joanne Dymek, Jessy Ryan, David Jayabalan, Selina Chen-Kiang, Scott Ely, John P. Leonard, Morton Coleman, Ruben Niesvizky
Journal: Blood (2006)