tbuckley/cabot-search huggingface dataset:
Managing chronic myeloid leukaemia in the elderly with intermittent imatinib treatment
Authors: D Russo, M Malagola, C Skert, V Cancelli, D Turri, P Pregno, M Bergamaschi, M Fogli, N Testoni, A De Vivo, F Castagnetti, E Pungolino, F Stagno, M Breccia, B Martino, T Intermesoli, G R Cambrin, G Nicolini, E Abruzzese, M Tiribelli, C Bigazzi, E Usala, S Russo, A Russo-Rossi, M Lunghi, M Bocchia, A D'Emilio, V Santini, M Girasoli, R Di Lorenzo, S Bernardi, A Di Palma, B M Cesana, S Soverini, G Martinelli, G Rosti, M Baccarani
Journal: Blood Cancer Journal (2015)

Abstract The aim of this study was to investigate the effects of a non-standard, intermittent imatinib treatment in elderly patients with Philadelphia-positive chronic myeloid leukaemia and to answer the question on which dose should be used once a stable optimal response has been achieved. Seventy-six patients aged ⩾65 years in optimal and stable response with ⩾2 years of standard imatinib treatment were enrolled in a study testing a regimen of intermittent imatinib (INTERIM; 1-month on and 1-month off). With a minimum follow-up of 6 years, 16/76 patients (21%) have lost complete cytogenetic response (CCyR) and major molecular response (MMR), and 16 patients (21%) have lost MMR only. All these patients were given imatinib again, the same dose, on the standard schedule and achieved again CCyR and MMR or an even deeper molecular response. The probability of remaining on INTERIM at 6 years was 48% (95% confidence interval 35–59%). Nine patients died in remission. No progressions were recorded. Side effects of continuous treatment were reduced by 50%. In optimal and stable responders, a policy of intermittent imatinib treatment is feasible, is successful in about 50% of patients and is safe, as all the patients who relapsed could be brought back to optimal response.
A persistent vulval ulcer
Authors: Catriona M Maybury, Andrew Pink, Fiona Lewis
Journal: BMJ (2015)

An 84 year old woman presented with a seven month history of a gradually enlarging, tender, shallow ulcer on the outer aspect of the right labium majus (fig 1⇓). She reported no other active or previous skin or mucosal problems and had a background of ischaemic heart disease, hypertension, hypercholesterolaemia, and type II diabetes. She was taking lisinopril, indapamide, atenolol, atorvastatin, aspirin, isosorbide mononitrate, nicorandil, metformin, and omeprazole. She was a non-smoker and there was no family history of skin disease.





### 1. What should you cover in the history and examination of a patient with vulval ulceration?

#### Short answer

Take a detailed history. A thorough examination of the vulva, vagina, and perianal area is needed, followed by a general skin examination, including other mucosal sites. 

#### Discussion

Ask about the onset, triggers, and duration of the ulcer as well as the presence of fever or systemic symptoms. Has the patient had a previous episode? Does the patient have any other immune mediated problems? What personal care products does the patient use? Have smear test results been normal? Does the patient have a new partner? A full drug, sexual, and travel history could give important clues.

Examine the vulva, noting the number and size of ulcers. Is there associated excoriation, fissuring, or oedema? In addition, examine the vagina, perineum, perianal skin, and inguinal lymph nodes. A general examination of the skin, eyes, and mouth may also provide vital clues to the diagnosis. For example, eczema at other sites may raise the possibility of contact dermatitis.

### 2. What differential diagnoses should you consider in a patient with vulval ulceration?

#### Short answer

Differential diagnoses include infection (such as herpes simplex), inflammation, cancer, trauma, and iatrogenic (drug induced) causes. Infection is a more …
Genetic factors influencing the risk of multiple myeloma bone disease
Authors: D C Johnson, N Weinhold, J Mitchell, B Chen, O W Stephens, A Försti, J Nickel, M Kaiser, W A Gregory, D Cairns, G H Jackson, P Hoffmann, M M Noethen, J Hillengass, U Bertsch, B Barlogie, F E Davis, K Hemminki, H Goldschmidt, R S Houlston, G J Morgan
Journal: Leukemia (2015)

A major complication of multiple myeloma (MM) is the development of osteolytic lesions, fractures and bone pain. To identify genetic variants influencing the development of MM bone disease (MBD), we analyzed MM patients of European ancestry (totaling 3774), which had been radiologically surveyed for MBD. Each patient had been genotyped for ~6 00 000 single-nucleotide polymorphisms with genotypes for six million common variants imputed using 1000 Genomes Project and UK10K as reference. We identified a locus at 8q24.12 for MBD (rs4407910, OPG/TNFRSF11B, odds ratio=1.38, P=4.09 × 10–9) and a promising association at 19q13.43 (rs74676832, odds ratio=1.97, P=9.33 × 10–7). Our findings demonstrate that germline variation influences MBD and highlights the importance of RANK/RANKL/OPG pathway in MBD development. These findings will contribute to the development of future strategies for prevention of MBD in the early precancerous phases of MM.
Tuberculosis elimination, patients' lives and rational use of new drugs: revisited
Authors: Simon Tiberi, Lia D'Ambrosio, Saverio De Lorenzo, Pietro Viggiani, Rosella Centis, Giovanni Battista Migliori
Journal: European Respiratory Journal (2015)

The World Health Organization (WHO) has recently published a framework on tuberculosis (TB) elimination opening debates on elimination and multidrug-resistant (MDR)-TB [1, 2]. The document highlights MDR-TB as a core area, emphasising the moral duty of preventing the selection of MDR-TB (by treating susceptible cases correctly with first-line drugs) and the necessary efforts to treat it when diagnosed. Unfortunately, treating MDR- and extensively drug-resistant (XDR)-TB is much more onerous, lengthy and terribly expensive; treatment outcomes remain suboptimal, adverse events being frequent and severe [3–6]. The availability of new drugs has offered new possibilities for saving patients who were not previously treatable and posed new challenges related to their rational use in order to prevent selection of resistant strains of Mycobacterium tuberculosis [7–10]. The importance of not fostering resistance and conserving new TB drugs for subsequent generations <http://ow.ly/TkR8K>
Beclin 1 regulates neuronal transforming growth factor-β signaling by mediating recycling of the type I receptor ALK5
Authors: Caitlin E. O’Brien, Liana Bonanno, Hui Zhang, Tony Wyss-Coray
Journal: Molecular Neurodegeneration (2015)

Beclin 1 is a key regulator of multiple trafficking pathways, including autophagy and receptor recycling in yeast and microglia. Decreased beclin 1 levels in the CNS result in neurodegeneration, an effect attributed to impaired autophagy. However, neurons also rely heavily on trophic factors, and signaling through these pathways requires the proper trafficking of trophic factor receptors. We discovered that beclin 1 regulates signaling through the neuroprotective TGF-β pathway. Beclin 1 is required for recycling of the type I TGF-β receptor ALK5. We show that beclin 1 recruits the retromer to ALK5 and facilitates its localization to Rab11+ endosomes. Decreased levels of beclin 1, or its binding partners VPS34 and UVRAG, impair TGF-β signaling. These findings identify beclin 1 as a positive regulator of a trophic signaling pathway via receptor recycling, and suggest that neuronal death induced by decreased beclin 1 levels may also be due to impaired trophic factor signaling.
Timing of access to outpatient palliative care services: What’s in a name?
Authors: Shalini Dalal, Sebastian Bruera, Charles Masino, Janet L. Williams, Yi Zhang, Emmanuel Obasi, Natalie Schuren, Eduardo Bruera
Journal: Journal of Clinical Oncology (2014)

10 Background: We have previously shown the name “palliative” to be a barrier to early palliative care (PC) referral. Further, following service name change to supportive care (SC) in late 2007, we immediately observed an increased survival time of about 1.5 months from PC consultation suggesting earlier referral following the name change. This study was conducted to determine the timing of patient access to outpatient PC services over several years period after the name change. Methods: Records of consecutive outpatient referrals in fiscal years (FY) 2007 (pre-name change), 2008 (transition period), 2009-2013 (post-name change) were reviewed. Timing of PC access was determined by 3 time intervals: (a) survival from PC consultation; (b) advanced cancer diagnosis to PC (c) hospital registration to PC; Kruskal-Wallis, Kaplan Meir and Cox regression models were used. Results: 6,624 patients had their first outpatient PC consultation during FY 2007 to 2013. Each year we observed a consistent increase in new patient referrals, as well as a longer median survival time from PC consultation (logrank &lt;0.0001). The table below shows median survival and hazard ratio (HR) for FYs 2008-2013 as compared to FY 2007. In FY 2013 there were 63% greater number of outpatient referrals as compared to FY 2007 (p &lt;0.0001), longer median survival (months) (7.9 vs 4.8; p &lt;0.001), and shorter median interval (months) from advanced cancer diagnosis (5.9 vs 7.8; p&lt; 0.002) and from hospital registration (6.6 vs 14.8; p&lt; 0.0001) to PC consultation. Conclusions: Following the name change of service from PC to SC, there has been consistent annual increase in new patient referrals as well as earlier access to outpatient PC services. The outpatient setting facilitates earlier patient access to SC/PC services and should be established in more centers. [Table: see text]
Abstract 15869: Off-Pump Coronary Artery Bypass Grafting is Associated With Higher Rate of Percutaneous Coronary Intervention at 8-Year Follow-Up
Authors: Fabio Barili, Stefano Rosato, Paola D’Errigo, Alessandro Parolari, Lorenzo Menicanti, Fulvia Seccareccia
Journal: Circulation (2014)

Introduction: The debate on the advantages and limitations of off-pump (OPCAB) vs on pump CABG has not still arrived to a conclusion and concerns still exist on graft patency. This study was designed to compare the impact on mortality and morbidity of OPCAB and on-pump CABG, with a specific focus on mid-term need for percutaneous cardiac intervention (PCI). Methods: The PRIORITY project was designed to evaluate the mid-long term outcomes of 2 large prospective multicenter cohort studies on CABG conducted between 2002-2004 and 2007-2008. Data on isolated CABG performed both on-pump and off-pump were derived from clinical dataset and linked to 2 administrative datasets. Time-to event analyses were performed in a competing risk framework to evaluate the potential role of surgical techniques on outcomes. Results: The population consisted of 11020 patients who underwent isolated CABG (27.2% OPCAB). Several risk factor but surgical technique independently affected in-hospital mortality. The incidence of postoperative PCI was significantly higher in OPCAB group (p&lt;0.05) and the multivariate logistic regression demonstrated that on-pump CABG was the only factor that protects from PCI after surgery (OR 0.61). Although unadjusted long-term survival was significantly worst for OPCAB (Log-rank p-value 0.00), the adjustment for factors found significant in the univariate analysis did not confirm OPCAB as a risk factor for mortality (hazard ratio was 0.96 ± 0.05, p-value 0.407). On the contrary, the significantly better cumulative incidence function of hospitalization for PCI at follow-up (Gray test p-value 0.00) in the on-pump group was confirmed even by the adjustment for confounding factors (p-value 0.00, adjusted hazard ratio 0.70 ± 0.07) and hence OPCAB was demonstrated to be an independent risk factor for PCI with an hazard that is 42% higher than on-pump CABG. Conclusions: This study demonstrated that OPCAB did not affect short and long-term mortality. Nonetheless, it was a risk factor for re-hospitalization for PCI.
In veterans with PTSD, mindfulness-based group therapy reduced symptom severity
Authors: Patrick G. O’Malley
Journal: Annals of Internal Medicine (2015)

ACP Journal Club15 December 2015In veterans with PTSD, mindfulness-based group therapy reduced symptom severityPatrick G. O'Malley, MD, MPH, FACPPatrick G. O'Malley, MD, MPH, FACPUniformed Services University of the Health Sciences, Bethesda, Maryland, USA (P.G.O.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2015-163-12-009 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationPolusny MA, Erbes CR, Thuras P, et al. Mindfulness-based stress reduction for posttraumatic stress disorder among veterans: a randomized clinical trial. JAMA. 2015;314:456-65. https://pubmed.ncbi.nlm.nih.gov/26241597Clinical Impact RatingsGIM/FP/GP: Mental Health: Reference1. Steenkamp MM, Litz BT, Hoge CW, Marmar CR. Psychotherapy for military-related PTSD: a review of randomized clinical trials. JAMA. 2015;314:489-500. [PMID: 26241600] Google Scholar Author, Article, and Disclosure InformationAffiliations: Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA (P.G.O.)This article was published at Annals.org on 1 December 2015. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byTrauma- and Stressor-Related History and Symptoms Predict Distress Experienced during a Brief Mindfulness Meditation Sitting: Moving toward Trauma-Informed Care in Mindfulness-Based TherapyTreatment Engagement and Outcomes of Mindfulness-Based Cognitive Therapy for Veterans with Psychiatric Disorders"That Guy, Is He Really Sick at All?" An Analysis of How Veterans with PTSD Experience Nature-Based TherapyRationale, design, and implementation of a clinical trial of a mindfulness-based relapse prevention protocol for the treatment of women with comorbid post traumatic stress disorder and substance use disorder 15 December 2015Volume 163, Issue 12Page: JC9KeywordsDepressionGlobal healthMental health therapiesPosttraumatic stress disorderPsychiatry and mental healthQuality of lifeQuestionnairesVeteran care ePublished: 15 December 2015 Issue Published: 15 December 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Impact of EGFR and KRAS genotype on outcomes in a clinical trial registry of NSCLC patients initially treated with erlotinib or gefitinib
Authors: D. M. Jackman, L. V. Sequist, L. Cioffredi, M. Gallegos Ruiz, P. A. Janne, G. Giaccone, V. A. Miller, B. E. Johnson
Journal: Journal of Clinical Oncology (2008)

8035 Background: There is increasing interest in the impact of EGFR and KRAS genotype on patterns of response and resistance NSCLC pts treated with gefitinib or erlotinib. We created a mutation registry to track protocol-based clinical outcomes with specific mutations in NSCLC pts initially treated with an EGFR-TKI. Methods: To date, 5 clinical trials performed in the US and Europe have been included in this registry. These include: 1) erlotinib in pts age > 70 yrs; 2) erlotinib in unselected NSCLC pts; 3) gefitinib in pts with known EGFR mutations; 4) erlotinib in pts with bronchioloalveolar carcinoma (BAC) or adenocarcinoma with BAC features; and 5) erlotinib for women with adenocarcinoma who were former or never smokers. The registry includes only chemo-naïve pts, to assess the impact of EGFR-TKI’s on tumors that have not been exposed to the effects of cytotoxic chemotherapy. Results: 290 previously untreated pts have been enrolled and treated in these 5 trials from 2003 until the present. 277 chemo-naive pts were tested for EGFR mutations, and 180 were tested for KRAS mutations. A total of 121 mutations in EGFR or KRAS were detected. 75 pts had a sensitizing EGFR mutation. (RR = 63%, median PFS=11.4 m, median OS=23.8 m). Pts with exon 19 deletions had prolonged median TTP (13.0 vs 9.7 m) and median OS (30.8 vs 14.8 m) compared with pts with an L858R mutation. In the 75 pts found to have sensitizing EGFR mutations, there was no correlation between clinical outcomes and either smoking status, gender, or the type of EGFR-TKI administered (erlotinib vs gefitinib). KRAS mutations, EGFR exon 20 insertions, and T790M mutations were associated with resistance to EGFR-TKI therapy. There were no clinical responses in this group. For 40 pts with KRAS mutations alone, median progression-free survival was only 3.3 months; overall survival was 13.0 months. Conclusions: EGFR and KRAS genotype have an important impact on predicting clinical outcomes to treatment with an EGFR-TKI. The creation of a central genotype registry may help to yield more powerful insight into roles of these and other specific mutations and help guide treatment decisions. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca, Boehringer Ingelheim, Genentech, Genzyme, Roche Roche AstraZeneca, Genentech, Pfizer Genzyme, MolecularMD
Intracoronary Versus Intravenous Abciximab Bolus in Patients With ST-Segment Elevation Myocardial Infarction
Authors: Steffen Desch, Jochen Wöhrle, Rainer Hambrecht, Harald Rittger, Ralf Birkemeyer, Bernward Lauer, Petra Neuhaus, Oana Brosteanu, Peter Sick, Matthias Pauschinger, Sebastian Kerber, Klaus Kleinertz, Suzanne de Waha, Ingo Eitel, Gerhard Schuler, Holger Thiele
Journal: Journal of the American College of Cardiology (2013)
A Young Woman with Spotty Pigmentation, Acromegaly, Acoustic Neuroma and Cardiac Myxoma: Carney's Complex
Authors: P I Mansell, E Higgs, J P D Reckless
Journal: Journal of the Royal Society of Medicine (1991)

Case report A woman presented in 1981 at age 27 years with dizziness, diplopia, dysarthria and left arm weakness. She had leftsided sensorineural deafness, papilloedema and acromegalic features. She also described a pigmented spot on her left cheek which had faded at about age 9. She had long-standing mild wasting in the left leg following polio. A CT scan revealed a left cerebellopontine angle tumour and also a pituitary tumour with suprasellar extension. She underwent urgent decompression ofthe posterior fossa. A large acoustic neuroma was subsequently removed, with unavoidable sacrifice of the left facial nerve. Acromegaly was confirmed (Table 1) and she underwent transethmoidal hypophysectomy together with hypoglossal-facial nerve anastomosis to improve her facial palsy. A postoperative CT scan showed apparent complete removal ofboth intracranial tumours, and pituitary function was preserved. Continuing excess growth hormone (GH) secretion has subsequently shown a modest response to bromocriptine (Table 1). In 1983 a dense right hemiplegia occurred. A CT scan showed a large infarction in the left middle cerebral artery territory. Angiography revealed intraluminal obstruction of the left internal carotid artery, presumably due to embolization from a large left atrial myxoma demonstrated on echocardiography. The cardiac tumour was removed surgically. Grand mal fits occurred in 1984 and were well controlled on phenytoin. A few months later she became severely unwell with fever, lymphadenopathy and erythema multiforme. Initially this was thought to be a reaction to phenytoin, which was stopped. However, multiple milder episodes have continued and may be due to systemic effects of the myxoma. Four recurrent cardiac myxomas were removed in 1985 and two in 1987. A right homonymous hemianopia developed
Efficacy, safety, bone and metabolic effects of HIV nucleoside reverse transcriptase inhibitor BMS-986001 (AI467003): a phase 2b randomised, controlled, partly blinded trial
Authors: Samir K Gupta, Grace A McComsey, John Lombaard, Juan Echevarría, Catherine Orrell, Anchalee Avihingsanon, Olayemi Osiyemi, Mario Santoscoy, Neelanjana Ray, David A Stock, Samit R Joshi, George J Hanna, Max Lataillade
Journal: The Lancet HIV (2015)
Margaret McCartney: Blaming doctors won’t reduce antibiotic overuse
Authors: Margaret McCartney
Journal: BMJ (2015)

Seeing movement promotes survival. It results from an uncertain interplay between evolution and experience, making it hard to isolate the drivers of computational architectures found in brains. Here we seek insight into motion perception using a neural network (MotionNet) trained on moving images to classify velocity. The network recapitulates key properties of motion direction and speed processing in biological brains, and we use it to derive, and test, understanding of motion (mis)perception at the computational, neural, and perceptual levels. We show that diverse motion characteristics are largely explained by the statistical structure of natural images, rather than motion per se. First, we show how neural and perceptual biases for particular motion directions can result from the orientation structure of natural images. Second, we demonstrate an interrelation between speed and direction preferences in (macaque) MT neurons that can be explained by image autocorrelation. Third, we show that natural image statistics mean that speed and image contrast are related quantities. Finally, using behavioral tests (humans, both sexes), we show that it is knowledge of the speed-contrast association that accounts for motion illusions, rather than the distribution of movements in the environment (the “slow world” prior) as premised by Bayesian accounts. Together, this provides an exposition of motion speed and direction estimation, and produces concrete predictions for future neurophysiological experiments. More broadly, we demonstrate the conceptual value of marrying artificial systems with biological characterization, moving beyond “black box” reproduction of an architecture to advance understanding of complex systems, such as the brain. <b>SIGNIFICANCE STATEMENT</b> Using an artificial systems approach, we show that physiological properties of motion can result from natural image structure. In particular, we show that the anisotropic distribution of orientations in natural statistics is sufficient to explain the cardinal bias for motion direction. We show that inherent autocorrelation in natural images means that speed and direction are related quantities, which could shape the relationship between speed and direction tuning of MT neurons. Finally, we show that movement speed and image contrast are related in moving natural images, and that motion misperception can be explained by this speed-contrast association not a “slow world” prior.