tbuckley/cabot-search huggingface dataset:
Boils—A Modern Take on the Plague of Egypt
Authors: Veronica Rodriguez, Eric Laurent Maranda, Jacqueline Cortizo, Aleksandra Augustynowicz, Lauren Duffey Crow, Joaquin J. Jimenez
Journal: JAMA Dermatology (2016)

Before modern science could explain ancient phenomena, people turned to religion and faith for answers. The Bible has long provided guidance for many religions, but it is often underappreciated as a historical text with insights into medical afflictions.
Recurrent otalgia in adults
Authors: Samuel Finnikin, Alistair Mitchell-Innes
Journal: BMJ (2016)

#### What you need to know

A 43 year old man presents with right sided earache. He says he’s had two or three similar episodes in the past year, which were treated elsewhere with drops. He’s not sure if it’s always the same ear

Earache or pain is a common presenting problem, usually caused by otitis media or otitis externa.1 Although data on the causes of recurrent otalgia are lacking, one year prevalence of otitis externa among UK adults is more than 1%, indicating a substantial burden of disease.2 Rarely eustachian tube dysfunction, mastoiditis, referred pain, or malignancy can present with recurrent ear pain.

Find out whether the pain is primary (originating from the ear) or secondary (referred). Malignancy tends to cause unilateral symptoms. Cover associated otological symptoms—for example, deafness and otorrhoea—and take a thorough ear, nose, and throat history, including previous conditions or surgery to rule out secondary otalgia. Think beyond the ear; recurrent otalgia can be referred from elsewhere. Ask about problems with swallowing, chewing, and facial …
Development of a nomogram to predict progression-free survival in patients with platinum-sensitive recurrent ovarian cancer based on the CALYPSO trial.
Authors: C. K. Lee, E. Guardiola, T. Hogberg, M. Friedlander, J. Bentley, U. Denison, I. B. Vergote, C. Pisano, G. Parma, P. Wimberger
Journal: Journal of Clinical Oncology (2010)

5105 Background: Patients (pts) with platinum-sensitive recurrent ovarian cancer (ROC) constitutes a heterogeneous group with variable prognosis. Standard definitions of platinum sensitivity cannot accurately predict survival outcomes. We seek to develop a prognostic nomogram using data from the CALYPSO trial comparing carboplatin-pegylated liposomal doxorubicin (CPLD) or carboplatin-paclitaxel (CP) therapy in ROC. Methods: The proportional hazards model, stratified by treatment arm, was used to develop the multivariable model (nomogram) for RECIST progression-free survival (PFS) based on pretreatment and patient demographic characteristics. Pts were grouped into high (score > 275), medium (score 125-275), and low (score < 125) risk groups. Results: 955 pts with a median PFS of 11.7 months (95% CI 11.0-11.9) were eligible. The following parameters predicted PFS significantly and independently: prior chemotherapy treatment ≤ 12 months, >1 metastatic site, size of largest tumor, elevated white blood cell, and elevated CA125. The nomogram provided good prognostic determination for these patients (Table). The concordance index between the observed and predicted survival was 0.637. A good agreement was evident between the actual and nomogram predicted PFS probabilities at 12 months. Stratification by risk groups suggested a trend for enhanced treatment benefit with CPLD over CP in the high-risk patients (HR = 1.06 [low risk], 0.80 [medium risk], 0.61 [high risk]) but test of treatment-by-risk group interaction is nonsignificant (p=0.22). Conclusions: A nomogram that combines 5 baseline characteristics improves prognostication of PFS and enabled the stratification of platinum-sensitive ROC pts into 3 risk groups. This risk grouping may be a useful tool for individualization of treatment and future stratification for pts in randomized trials. Risk group Median PFS Hazard ratio of disease progression across the whole risk group HR 95% CI Low (n=229) 16.1 1.00 – Medium (n=517) 11.7 2.17 1.75-2.70 High (n=209) 9.0 3.94 3.08-5.05 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering-Plough
Novel target of lapatinib enhances anti-tumor activity via TRAIL sensitization
Authors: Nathan Dolloff, Patrick Mayes, David Dicker, Robin Humphreys, Wafik El-Deiry
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

835 

The anti-Her2 and anti-EGFR dual kinase inhibitor lapatinib (Tykerb) in combination with capecitabine (Xeloda) was approved by the FDA on March 13, 2007 for treatment of Her2(+) breast cancer patients who received prior therapy with anthracyclines, taxanes and Herceptin. We hypothesized that targeting cancer cell survival pathways with lapatinib may synergize with TRAIL, which initiates extrinsic apoptotic cell death, and this may be of utility in therapy of solid tumors. We initially confirmed the high sensitivity of high Her2-expressing SKBR3 and BT474, and resistance of low Her2-expressing MDA-MB-231 and MDA-MB-468 breast cancer cell lines. In contrast, we identified a number of colon cancer cell lines with (+) EGFR (HCT116, SW480, HT29) or (+) Her2 (HCT116 and HT29) expression that were resistant to lapatinib up to 20 μM. SW620 expressed no detectable EGFR and low levels of Her2, and was also resistant to lapatinib. Lapatinib was found to sensitize TRAIL-resistant SW620, SW480-R6 and HT29 colon carcinoma cells to TRAIL-induced apoptosis, as determined by propidium iodide staining followed by FACS analysis, and Western blot analysis of caspase-3, 8, 9, and PARP processing. TRAIL-sensitization was evident with lapatinib concentrations higher than the EGFR and Her2 IC50s but similar to patient plasma concentrations achieved in clinical trials. In addition to recombinant TRAIL, lapatinib enhanced apoptosis triggered by agonistic TRAIL receptor antibodies mapatumumab and lexatumumab. Lapatinib sensitization to TRAIL was accompanied by up-regulation of death receptor (DR4 and DR5) expression and induction of Mcl-1 fragmentation. These novel effects are unrelated to EGFR and/or Her2 inhibition, as treatment with EGFR and Her2-specific inhibitors, AG1478 and AG825, respectively, alone or in combination, failed to recapitulate lapatinib-mediated TRAIL sensitization. The current studies point to a novel therapeutic combination of lapatinib and TRAIL or TRAIL receptor-targeted agonist antibodies. This combinatorial approach may be effective in colon and other tumors, and provides a preclinical mechanistic rationale for the anti-tumor effects.
Strengthening the Reporting of Observational Studies in Epidemiology for Newborn Infection (STROBE-NI): an extension of the STROBE statement for neonatal infection research
Authors: Elizabeth J A Fitchett, Anna C Seale, Stefania Vergnano, Michael Sharland, Paul T Heath, Samir K Saha, Ramesh Agarwal, Adejumoke I Ayede, Zulfiqar A Bhutta, Robert Black, Kalifa Bojang, Harry Campbell, Simon Cousens, Gary L Darmstadt, Shabir A Madhi, Ajoke Sobanjo-ter Meulen, Neena Modi, Janna Patterson, Shamim Qazi, Stephanie J Schrag, Barbara J Stoll, Stephen N Wall, Robinson D Wammanda, Joy E Lawn
Journal: The Lancet Infectious Diseases (2016)
Macro Trends and the Future of Public Health Practice
Authors: Paul Campbell Erwin, Ross C. Brownson
Journal: Annual Review of Public Health (2016)

Public health practice in the twenty-first century is in a state of significant flux. Several macro trends are impacting the current practice of governmental public health and will likely have effects for many years to come. These macro trends are described as forces of change, which are changes that affect the context in which the community and its public health system operate. This article focuses on seven such forces of change: the Patient Protection and Affordable Care Act, public health agency accreditation, climate change, health in all policies, social media and informatics, demographic transitions, and globalized travel. Following the description of each of these, this article then turns to possible approaches to measuring, tracking, and understanding the impact of these forces of change on public health practice, including the use of evidence-based public health, practice-based research, and policy surveillance.
Impact of primary coronary angioplasty delay on myocardial salvage, infarct size and microvascular damage in patients with ST-elevation myocardial infarction: insight from cardiovascular magnetic resonance. Melvin Judkins Young Investigator Award
Authors: Chiara Bucciarelli-Ducci, Marco Francone, Iacopo Carbone, Emanuele Canali, Raffaele Scardala, Francesca Calabrese, Gennaro Sardella, Massimo Mancone, Carlo Catalano, Francesco Fedele, Roberto Passariello, Jan Bogaert, Luciano Agati
Journal: Circulation (2009)
P1-019: Bronchoscopic cryotherapy treatment of obstructive tumors with respiratory failure
Authors: EunJoo Lee, Eunsil Ha, Sewha Yoo, Sungyong Lee, Jehyeong Kim, Chol Shin, Jaejeong Shim, Kwangho In, Kyungho Kang, Kihwan Jong
Journal: Journal of Thoracic Oncology (2007)
D6-02: Patient-to-patient and tumor sub-sample variations of gene expression in NSCLC
Authors: Michael A. Meister, Anton Belousov, Elizabeth C. Xu, Thomas R. Muley, Philipp A. Schnabel, Hans Hoffmann, Hendrik Dienemann, Heinz Bodenmueller, Werner Zolg, Felix J. Herth
Journal: Journal of Thoracic Oncology (2007)
Granulocytic Sarcoma, A Single-Institution Survey of Clinical Presentation and Trajectory
Authors: Hossein Sadrzadeh, Nathan Deysher, Layli Jamali, Andrew M. Brunner, Benjamin J. Drapkin, Karen K. Ballen, Eyal C. Attar, Philip C. Amrein, Steven L. McAfee, Amir T Fathi
Journal: Blood (2012)
BMA Council to consider options before proceeding with five day strikes
Authors: Susan Mayor
Journal: BMJ (2016)

The BMA Council is set to debate the next steps for junior doctors in their contract dispute at a meeting on Wednesday 14 September, against a backdrop of growing calls from junior doctors to ballot members again before pressing ahead with the five day strikes planned for October, November, and December.

Last week the BMA called off a five day strike that was due to start on Monday 12 September after thousands of junior doctors contacted the BMA to express concern about the safety of patients in the event of such a prolonged withdrawal of their labour.1

Several junior doctors have since raised the option of a second ballot in Twitter discussions. “The BMA has a duty to see …
A Phase II Trial of Bendamustine, Bortezomib, and Rituximab in Patients with Previously Untreated Low Grade Lymphoma
Authors: Ian W. Flinn, Thomas J. Ervin, Ralph V. Boccia, Douglas B. Flora, J. Daniel Cuevas, Dana S. Thompson, Dianna L. Shipley, Jesus G. Berdeja
Journal: Blood (2015)
Inhibition of interleukin-1 signaling enhances elimination of tyrosine kinase inhibitor–treated CML stem cells
Authors: Bin Zhang, Su Chu, Puneet Agarwal, Victoria L. Campbell, Lisa Hopcroft, Heather G. Jørgensen, Allen Lin, Karl Gaal, Tessa L. Holyoake, Ravi Bhatia
Journal: Blood (2016)
Jejunal catheter placement for levodopa–carbidopa infusion in a patient with Billroth I gastrectomy
Authors: Pave Markos, Branko Bilic, Vladimir Miletic, Nadan Rustemovic
Journal: Endoscopy (2016)

A new treatment method of continuous delivery of a gel suspension (20 mg/mL levodopa plus 5 mg/mL carbidopa; Duodopa, Abbvie, Maidenhead, UK) to the small intestine via a jejunal tube has recently been used with increased frequency in selected patients with advanced Parkinson's disease [1]. Usually a classic percutaneous endoscopic gastrostomy (PEG) kit is placed first, then a pigtail catheter is introduced through the PEG and deployed in the jejunum; a portable pump can then be attached externally [2]. There are no reports in the literature of levodopa–carbidopa infusion pump placement in patients with gastric resections.
Abstract 18406: Ulk1 Induces Mitochondrial Autophagy Through Rab9-dependent Phagophore Formation in Cardiomyocytes <i>(Best of Basic Science Abstract)</i>
Authors: Toshiro Saito, Junichi Sadoshima
Journal: Circulation (2015)

Rationale: Mitochondrial quality control mediated by mitochondrial autophagy (MA) is essential for cardiac homeostasis. Although the role of the Parkin-Pink1 pathway in MA is well established, recent reports have uncovered the existence of unconventional autophagy in mediating MA in embryonic reticulocytes and fibroblasts. Objective: To investigate the molecular mechanism of MA in cardiomyocytes (CMs) during energy stress. Methods and Results: MA in CMs was evaluated with mitochondria-targeted (Mito)-Keima, which fluoresces with a high 560nm/440nm ratio after lysosomal translocation. In control CMs, high ratio dots represented 1.1±0.3 % of the area in cells at baseline, and glucose deprivation (GD) upregulated this area to 6.7±0.6 % (p&lt;0.01), indicating stimulation of MA. Although knockdown of Ulk1 reduced the area to 1.3±0.1 % (p&lt;0.01) during GD, that of Atg7 did not (6.6±0.8 %), suggesting that MA takes place during GD in Ulk1-dependent but Atg7-independent fashion. Since Ulk1-dependent alternative autophagy utilizes membrane trafficking from the trans-Golgi to form autophagosomes, we examined the effect of Brefeldin A (BFA), an inhibitor of the membrane trafficking, on MA. Treatment with BFA reduced the high-ratio dot area to 0.4±0.1 % (p&lt;0.01) during GD without affecting the protein level of LC3-II, suggesting that MA induced by GD is mainly mediated by alternative autophagy. BFA did not suppress the Parkin-induced area of high-ratio dots, suggesting that GD-induced MA is distinct from Parkin-dependent MA. GFP-Rab9 formed puncta during GD. These puncta were upregulated in the presence of Bafilomycin, whereas they were downregulated by the knockdown of Ulk1 or Beclin1. The puncta merged with the acidic dots of Mito-Keima during GD. Treatment with Bafilomycin, which inhibits the fusion of autophagosomes with lysosomes, increased the puncta merged with neutral Mito-Keima during GD. RFP-Rab9 did not co-localize with GFP-LC3. These results indicate that Rab9 induces formation of autolysosomes or autophagosomes in MA independently of LC3. Knockdown of Rab9 reduced the area of Mito-Keima high-ratio dots to 3.3±0.4% during GD (p&lt;0.01). Conclusions: Ulk1 regulates Rab9-dependent phagophore formation and induces MA during energy stress in CMs.
Differential response of primary or secondary exon 13/14 and exon 17 c-kit mutant to nilotinib and sunitinib: Findings from a cell-based drug-screening platform
Authors: C. Chan, L. Chen, Y. Hsueh, W. Chuang, H. Lee, M. Huang, R. Heieh, W. Weng
Journal: Journal of Clinical Oncology (2009)

e15636 Background: Gastrointestinal stromal tumors (GIST) are frequently associated with mutation of c-kit oncogene that is accompanied with constitutional activation of c-kit protein. At present, imatinib is the drug of choice for unresectable or metastatic GIST, however, primary or acquired resistance to imatinib is frequently associated with the presence of an exon 13, 14 or 17 c-kit mutation. The current recommendations for GIST refractory to standard (400 mg/day) imatinib treatment include increasing dose of imatinib to 600–800 mg/day for tumors with primary exon 9 mutation or sunitinib. Several molecular targeted agents are also under investigation. With so many potential agents, personalized therapy based on c-kit mutant genotype for imatinib-resistant GIST deserves to explore. Methods: We prepared a series of c-kit cDNA constructs encoding mutant exon 9 (502AY insertion), 11 (V560D substitution and Δ555–576 deletion), 13 (V654A substitution), 14 (T670I substitution) and 17 (D820G and N822K substitutions) either alone or in combination to simulating the frequently occurred primary ± secondary c-kit mutants in GIST. We expressed these constructs in COS-1 cells to study the efficacy of different tyrosine kinase inhibitors (TKIs) on the autophosphorylation of various single or double mutant c- kit. Results: The efficacy of imatinib on single c-kit mutant was V560D &gt; Δ555–576 &gt; 502AY &gt; D820G or N822K, and ineffective for single and double mutants containing V654A or T670I. Sunitinib is a more potent inhibitor for single 502AY, D820G and N822K mutant than imatinib and nilotinib; while single V654A and T670I c-kit mutant are more sensitive to nilotinib. Interestingly, double exon 11 (V560D or Δ555–576)/V654A or T670I mutant c-kit are more sensitive to sunitinib; while exon 11 (V560D or Δ555–576)/D820G or N822K double mutant c-kit are more sensitive to nilotinib. Conclusions: Our system provides a useful platform to select/screen effective TKIs for GIST with single or double mutant c-kit. The findings of differential response of c-kit mutant to nilotinib and sunitinib may help to select therapy for GIST with primary or secondary exon 13 / 14 and exon 17 mutations. [Table: see text]
Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as a pharmacodynamic (PD) biomarker in phase I trials of the humanized monoclonal antibody (huMAb) anti-EGFL7 (MEGF0444A).
Authors: J. Fredrickson, I. Chang, M. Friesenhahn, E. Ashton, P. N. Munster, M. S. Gordon, D. S. Chen, L. Naumovski, A. de Crespigny, L. S. Rosen
Journal: Journal of Clinical Oncology (2011)

2539 Background: DCE-MRI allows for the functional analysis of tumor microcirculation and composition, and has been used to evaluate changes in vascular parameters in response to anti-angiogenic agents. In pre-clinical models, MEGF0444A resulted in anti-vascular, anti-angiogenic effects on tumor vasculature as well as inhibition of vascular re-growth in combination with anti-VEGF therapy. Based on these observations, DCE-MRI was incorporated as a PD marker in the MEGF0444A Phase 1a monotherapy trial and Phase 1b combination trial with bevacizumab (B). Methods: Both trials had a dose-escalation stage where DCE-MRI was optional, and a dose-expansion stage where it was mandatory, and two different doses of MEGF0444A were evaluated. Eligible patients had advanced solid tumors 2-10 cm in longest dimension (3-10 cm in liver) with intrathoracic lesions excluded. A standardized imaging protocol was implemented at three imaging sites. Two baseline scans were obtained prior to dosing on Cycle 1 Day 1 (C1D1) to assess reproducibility. On-treatment DCE-MRIs were performed on C1D15 and C2D8 (q3 wk dosing of MEGF0444A) in Phase 1a, and on C1D3 and C1D13 in Phase 1b (q2 wk dosing). Data were fit to a kinetic model to derive median values of vascular parameters such as Ktrans, and a linear mixed effects model was used to summarize results. Results: Across both studies, 109 scans were acquired and 90 (83%) were considered evaluable. Based on double baseline scans, the coefficient of variation (CV) for Ktrans was 10% in Phase 1a and 15% in Phase 1b. For pooled data In Phase 1a, the mean % change from baseline (CFB) in Ktrans was -15% at C1D15 and -17% at C2D8. In Phase 1b, the mean %CFB in Ktrans was -21% at C1D3. At C1D13, a trend in dose response was seen (-28%, -3%), pooled = -16%. Conclusions: DCE-MRI was successfully implemented across multiple imaging centers with a typical Phase I population. ΔKtrans and maintained response suggest potential vascular targeting by MEGF0444A as a single agent and in combination with B. These results, along with PK and PD data, support a 5 mg/kg q2 wk (flat dose equivalent, 400mg q2 or 600mg q3 wk) as the recommended Phase II dose.
Mixed Phenotype Acute Leukemia, T/Myeloid, NOS (MPAL-TM) Has a High DNMT3A Mutation Frequency and Carries Further Genetic Features of Both AML and T-ALL: Results of a Comprehensive Next-Generation Sequencing Study Analyzing 32 Genes
Authors: Wolfgang Kern, Vera Grossmann, Andreas Roller, Sandra Weissmann, Tamara Alpermann, Ulrike Schoeck, Claudia Haferlach, Susanne Schnittger, Torsten Haferlach, Alexander Kohlmann
Journal: Blood (2012)
Overtreating Hypertension
Authors: William Zinn
Journal: Annals of Internal Medicine (1992)

Letters15 September 1992Overtreating HypertensionWilliam Zinn, MDWilliam Zinn, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-117-6-536 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors:Kaplan (1) failed to address in his recent review of the overtreatment of hypertension whether merely treating rather than controlling hypertension is adequate for the prevention of morbid events. In the Systolic Hypertension in the Elderly Program (SHEP) (2) and the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) study (3), a relatively fixed dosage schedule was used and a number of elderly patients who were treated did not reach their target blood pressure level (28% in the case of the SHEP study). The authors did not do subgroup analysis to determine whether patients who did not...References1. Kaplan N. The appropriate goals of antihypertensive therapy: neither too much nor too little. Ann Intern Med. 1992;116:686-90. LinkGoogle Scholar2. . Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 1991;265:3255-64. CrossrefMedlineGoogle Scholar3. DahlofLindholmHanssonScherstenEkbomWester BLLBTP Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). Lancet. 1991;23;338: 1281-5. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Harvard Medical School Cambridge, MA 02139 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 September 1992Volume 117, Issue 6Page: 536-537KeywordsBlood pressureElderlyHypertension Issue Published: 15 September 1992 PDF DownloadLoading ...
Erratum: JAK2-V617F activating mutation in acute myeloid leukemia: prognostic impact and association with other molecular markers
Authors: C Vicente, I Vázquez, N Marcotegui, A Conchillo, C Carranza, G Rivell, E Bandrés, I Cristobal, I Lahortiga, M J Calasanz, M D Odero
Journal: Leukemia (2007)
Total liver volume measurement by CT corrected for body surface area is an objective parameter of the extent of polycystic liver disease
Authors: Frederik J Temmerman, Ragna Vanslembrouck, Walter Coudyzer, Bert Bammens, Wim Laleman, Chris Verslype, David Cassiman, Werner Van Steenbergen, Frederik Nevens, Jos van Pelt, Jacques Pirenne
Journal: Hepatology (2011)
“Something has to give,” warns leader of NHS trusts over finances
Authors: Anne Gulland
Journal: BMJ (2016)

The leader of the body representing NHS trusts has warned that the NHS is close to breaking point and that, if there is not extra funding, it must make “quick, clear choices on what gives.”

Writing in the Observer newspaper, Chris Hopson, chief executive of NHS Providers, made an impassioned plea for an honest public debate over the state of NHS finances. He wrote that national health chiefs and political leaders had to acknowledge publicly that the “NHS can no longer deliver what is …