tbuckley/cabot-search huggingface dataset:
RTRB-05DEFINING THE ROLE OF PROPHYLACTIC CRANIAL IRRADIATION IN NSCLC: A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE WORLD'S LITERATURE
Authors: Timothy Brown, Matthew Brennan, Minesh Mehta, Michael Glantz
Journal: Neuro-Oncology (2015)

INTRODUCTION: Brain metastases remain common in patients with  cell lung cancer despite markedly improved systemic therapy. Prophylactic cranial  (PCI) in NSCLC remains controversial even though nearly all studies show a clinically and statistically significant decrease in the rate of brain metastases. We present the results of a comprehensive meta-analysis to define the role of PCI in NSCLC. METHODS: An evidence-based literature search querying Medline and the Cochrane Database was completed with the assistance of an expert librarian using the search terms: prophylactic cranial irradiation AND non-small cell lung carcinoma. Primary outcomes were 1-year survival and the rate of brain metastases. Included studies were graded for level of evidence using AAN criteria. One-year survival was determined using pixel coordinates when not explicitly stated. Meta-analyses using a random effects model were performed using Cochrane software. RESULTS: The systematic review produced 112 unique citations. Seventeen studies were identified as potentially eligible for analysis. Of these, twelve studies provided information on the rate of brain metastases, and five provided data on 1-year survival. No study provided greater than Class III evidence. The meta-analysis showed a relative risk of brain metastases (PCI versus non-PCI) of 0.34 [95% CI 0.25-0.45], p < 0.001, NNT = 10. The relative risk for 1-year survival (PCI vs. non-PCI) did not achieve statistical significance (RR = 1.04 [95% CI 0.95-1.13]). Confidence in these results using GRADE criteria was low to very low. CONCLUSIONS: A systematic review of the literature demonstrates a dramatic reduction in the frequency of brain metastases in patients with NSCLC receiving PCI without an increase in one-year survival. Despite multiple randomized controlled trials, the quality of the evidence is low, however the flaws in study methodology are easily remediable. A multi-national effort to resolve this critical question should be a worldwide priority.
Longitudinal Electrophysiologic Assessment of Asymptomatic Patients with the Wolff–Parkinson–White Electrocardiographs Pattern
Authors: George J. Klein, Raymond Yee, Arjun D. Sharma
Journal: New England Journal of Medicine (1989)

Although most asymptomatic patients with the Wolff–Parkinson–White electrocardiographic pattern have a good prognosis, some die suddenly. The mechanism of sudden death is usually ventricular fibrillation, which is triggered by atrial fibrillation with a rapid ventricular response rate. Electrophysiologic testing has been proposed to identify asymptomatic patients who may be at risk for sudden death. Meaningful application of such testing requires a knowledge of whether the electrophysiologic measurements are reproducible over time. Consequently, we performed electrophysiologic studies on two occasions at least 36 months apart (mean ±SD, 54.7±14) in 29 asymptomatic patients with the pattern. Twenty-seven patients remained asymptomatic, and sustained supraventricular tachycardia developed in two during the follow-up period. Nine patients (31 percent) lost the capacity for preexcitation and anterograde conduction over the accessory pathway, which produces the Wolff–Parkinson–White pattern. The others had little change in measurements of conduction over the accessory pathway. Patients who lost conduction over the accessory pathway tended to be older (mean ±SD, 50±18 vs. 39±11 years; P = 0.06) than patients who retained preexcitation, and they had longer anterograde effective refractory periods at the first assessment (414±158 vs. 295±27 msec; P = 0.003). We conclude that a considerable number of asymptomatic patients with the Wolff–Parkinson–White pattern lose their capacity for anterograde conduction over the accessory pathway. This loss of capacity probably contributes to the low mortality among asymptomatic patients. (N Engl J Med 1989; 320:1229–33.)
‘Sideline Guidelines’ by Cleveland Clinic Innovations: a smartphone application for the on-field healthcare practitioner
Authors: Hopin Lee, Laura Struik, Osman Hassan Ahmed
Journal: British Journal of Sports Medicine (2016)

Sideline Guidelines —Cleveland Clinic Innovations.

Health and Fitness.

iOS 7.0 or later. Compatible with iPhone and iPad.

Free (no in-app purchases)—V.1.0 (9 July 2015).

A key role of the sports doctor, physiotherapist and athletic trainer is to detect, diagnose and treat sports injuries and medical emergencies on the sideline to ensure the health and safety of athletes.1 Sideline Guidelines, developed by Cleveland Clinic Innovations, is an app that is informed by a respected (US) national faculty, with the aim of assisting healthcare practitioners to manage sports injuries for high school, college and professional athletes from the sideline. The developers claim Sideline Guidelines to be the ‘first of its kind’.2 The overall purpose of this app is to provide sports …
High prevalence of restless legs syndrome in cancer patients undergoing chemotherapy: Relationship with anxiety, depression and quality of life perception
Authors: A. Saini, L. Ostacoli, E. Sguazzotti, S. Capogna, C. Castronovo, V. Dongiovanni, G. Gorzegno, P. M. Furlan, L. Dogliotti, A. Berruti
Journal: Journal of Clinical Oncology (2007)

9032 Background: The Restless Legs Syndrome (RLS) is one of the commonest neurological sensorimotor disorders consisting in periodic limbs movements during the sleeping time that lead to severe insomnia and quality of life deterioration. The prevalence of RLS in normal population is 7 and 11% in males and females respectively. RLS correlated with female sex and iron deficiency. Chronic pain, sensory polineuropathy and the use of dopamine antagonist drugs can induce or exacerbate RLS. Dopamine agonists are extremely active drugs in controlling RLS. The prevalence of RLS in cancer patients is unknown. Methods: The presence of RLS, by means of the essential diagnostic criteria provided by the International RLS Study Group (Allen RP, Sleep Med; 2003), was tested in 257 consecutive cancer patients (119 males and 138 females) with different malignancies belonging to two different Medical Oncology centres. All patients were receiving chemotherapy. Functional Assessment of Cancer Therapy General (FACT-G), Hospital Anxiety and Depression Scale (HADS) and Mini Mental Adjustment to Cancer Scale (Mini-MAC) questionnaires were administered concomitantly to assess the impact of RLS on quality of life, anxiety or depression and styles of coping, respectively. Results: RLS was present in 47 patients (18.3%), 14 males (11.8%) and 33 females (23.9%); (p=0.01). RLS directly correlated with pain (p&lt;0.0001), nausea (p&lt;0.001), worse physical well-being (p=0.007), emotional well- being (p=0.001) and functional well-being (p=0.02). RLS affected patients showed higher levels of anxiety (p&lt;0.001) and depression (p=0.001). The styles of coping consisting in anxious preoccupation and hopeless were also more represented in the RLS affected patients (p=0.04 and p=0.02 respectively) than their counterparts. Conclusions: RLS is frequent and underdiagnosed in cancer patients. It may cause anxiety, depression and quality of life deterioration. Early RLS detection and prompt introduction of dopamine agonists may improve patient quality of life. No significant financial relationships to disclose.
A longitudinal assessment of the quality of life (QOL) of older adults with newly diagnosed acute myeloid leukemia (AML): A pilot study
Authors: H. Kermalli, A. Schattner, G. Vikas, A. Schumacher, W. E. Berdel, J. Brandwein, M. D. Minden, A. Schuh, R. W. Wells, S. M. H. Alibhai
Journal: Journal of Clinical Oncology (2004)

8277 Background: Older patients with AML often have a poor prognosis and often do not tolerate intensive chemotherapy. When weighing alternate management strategies, impact upon QOL is an important consideration. However, there is limited published research in this area. Methods: Patients aged 60 or older with newly diagnosed AML were enrolled at diagnosis regardless of treatment intent. Patients were excluded if life expectancy was less than one month or they did not speak English. QOL was measured at baseline and at 1, 4, and 6 months. Questionnaires included the European Organization for the Research and Treatment of Cancer QLQ-C30 (global health, 5 QOL domains, 3 symptom domains) and the Functional Assessment of Cancer Therapy Anemia and Fatigue subscale. Demographic and clinical information was also recorded. Patients were stratified by intensive versus non-intensive treatment. Results: From June to December 2003, 14 patients (mean age 73) were enrolled. At baseline, global health, role function, and social function were the most affected domains. Fatigue was the predominant symptom. Among patients treated intensively, global health, role function, emotional function, cognitive function, and social function improved from baseline to 1-month and 4-month follow-up. Physical function and fatigue scores worsened at 1 month but improved by 4-months follow-up. Non-intensively managed patients had smaller improvements in global health, role function, cognitive function, and social function. Physical function and emotional function remained stable. Fatigue scores showed a similar pattern to intensively managed patients. Pain scores were higher in non-intensively managed patients. Conclusions: QOL in older patients appears to be significantly affected by AML. Intensive chemotherapy is associated with greater improvement or less decline in most domains of QOL and better control of pain but not fatigue. Further patient enrollment and follow-up may lead to an improved understanding of QOL in AML in older adults and may facilitate better symptom management and treatment decision-making. No significant financial relationships to disclose.
Renal Disease in Type I Glycogen Storage Disease
Authors: Y T Chen, R A Coleman, J I Scheinman, P C Kolbeck, J B Sidbury
Journal: New England Journal of Medicine (1988)

Although kidney enlargement occurs in Type I glycogen storage disease, renal disease has not been considered a major problem. Death from renal failure in three patients known to us prompted a study of renal function in this disorder. Of the 38 patients with Type I glycogen storage disease under our care, the 18 children under 10 years old had normal renal function. Fourteen of the 20 older patients (13 to 47 years) had disturbed renal function, manifested by persistent proteinuria; many also had hypertension, hematuria, or altered creatinine clearance. Progressive renal insufficiency developed in 6 of these 14 patients, leading to three deaths from renal failure. At the onset of proteinuria, creatinine clearance was increased in seven patients (3.05±0.68 ml per second per 1.73 m2 of body-surface area; range, 2.47 to 4.13 [normal range, 1.33 to 2.33 ml per second per 1.73 m2]). Renal biopsies were performed in three patients after an average of 10 years of proteinuria. All three biopsies demonstrated focal segmental glomerulosclerosis in various stages of progression. Our data suggest that chronic renal disease is a frequent and potentially serious complication of Type I glycogen storage disease. In addition to treating hypoglycemia vigorously, physicians should monitor renal function carefully in patients with this disorder. (N Engl J Med 1988; 318:7–11.)
Long-term cognitive function among testicular cancer survivors treated with chemotherapy
Authors: J. Skoogh, G. Steineck, U. K. Stierner, E. Cavllin-Ståhl, U. Olofsson, A. Wallin, M. Gatz, B. Johansson
Journal: Journal of Clinical Oncology (2008)

5035 Background: We have studied cognitive function among testicular cancer patients survivors treated with chemotherapy compared with those only treated surgically. Method: In Sweden, men diagnosed with non-seminomatous testicular cancer have prospectively been registered in SWENOTECA since 1981. During 2007 we followed up men diagnosed up to 2004; from the register we obtained clinical information about the treatment given. During a two-year period we developed a study-specific questionnaire primarily on cognitive functions. We also formulated questions about well-being and neurological symptoms. The questionnaire, extensively tested for validity, built on 40 in-depth interviews and a format developed at our division (Clinical Cancer Epidemiology). Results: We obtained information from 987/1220 (82%) testicular cancer patients survivors four to 21 years after the diagnosis. Prevalence of a “little, moderately or much” (versus none) affected well-being due difficulties “finding words and other language difficulties” was 17 percent among those having received no chemotherapy versus 36 percent among those having received 5 or more cycles, giving a prevalence ratio (“relative risk”, RR) of 2.1 with a 95 percent confidence interval of 1.4–3.1. Corresponding figures for “slow thinking speed” was 1.9 (1.2–3.0), “memory” 1.8 (1.2–2.7) and “concentration” 1.7 (1.2–2.4). We found statistically significant poorer results on 5 of 7 analyzed language questions for those treated with 5 cycles or more of chemotherapy compared with those only treated surgically. The highest risk was for ‘producing similar but incorrect words‘ were those treated with 5 cycles or more of chemotherapy had a 3.2 higher risk (95% CI, 1.5–6.8) compared with those only treated surgically. Five or more cycles, as compared to no chemotherapy, resulted in having decreased feeling of touch in finger and toes (RR 7.0, 3.1–15.9). Conclusion: Patients needing more than the 4 cycles of chemotherapy are at risk of developing not only neurological but also cognitive long-term side-effects, eg concerning language function, which can affect well-being. Our results can be used to provide patients (both before and after treatment) with information about cognitive side-effects that may develop due to chemotherapy. No significant financial relationships to disclose.
Early Diastolic Strain Rate in Relation to Systolic and Diastolic Function and Prognosis in Aortic Stenosis
Authors: Jordi S. Dahl, Sergio Barros-Gomes, Lars Videbæk, Mikael K. Poulsen, Issa F. Issa, Rasmus Carter-Storch, Nicolaj Lyhne Christensen, Anja Kumme, Patricia A. Pellikka, Jacob E. Møller
Journal: JACC. Cardiovascular imaging (2016)
Mutations in<i>NPC1L1</i>and Coronary Heart Disease
Authors: Uyenlinh L Mirshahi, David J Carey
Journal: New England Journal of Medicine (2015)

between lower thresholds for glycated hemoglobin (as well as albuminuria and possibly other variables of interest) and adverse cardiovascular events were beyond the scope of our study, we agree that such investigations would be valuable and should be pursued in future studies.In response to Magliano et al.: we agree that the proportion of deaths due to cardiovascular disease in our study is likely to be an underestimation and that cardiovascular disease probably contributed to a fair share of the deaths categorized as having diabetes as the underlying cause.However, because many of the deaths due to diabetes had multiple or unspecified complications (including cardiovascular disease), and furthermore, because we were not able to validate the final chain of events leading to death from the data in the register, we used a conservative approach.
Soundings: An oblique passion
Authors: Kevin Barraclough
Journal: BMJ (2005)

Throughout my life I have had a persistent, rather dilettante interest in mathematics. I dabble a little, drift away with pressures of work and family, but always seem to return.

It is, I think, the calm that draws me back. It is detached from the grit and noise of the medical world—a place of clean lines and perfect spheres, of abstract objects that glisten in the imagination in a sharp, multidimensional light. Sometimes I see them as solid shapes etched with dew. I suspect that this is very pathological.

I have mostly kept quiet about my interest as revealing it tends to provoke either incredulity or derision. I think part of the image problem lies with mathematicians themselves. They mostly have beards with dried soup stains, and an odd, childlike humour characterised by an abundance of puns, and they are prematurely good at crosswords. In fact they have all the attributes of a strange, priestly cult. They are unworldly, isolated, and unintelligible unless you are an initiate. They speak and write an arcane, runic script, which, somewhat bizarrely, seems to be the language of God.

It is this script that is, I think, one of the attractions for me. If I look at the mathematical notebooks I have kept over the years the symbols are rather beautiful. My handwriting has always been ugly. But the mathematical notation—the neat black narrative on the white page—seems a thing of beauty to me.

One of the things I find strange is that, despite covering quite a lot of mathematical ground over many years, I have rarely actually made it out of the 19th century. O level gets you past the Greeks. A level takes you as far as the 17th century. But it's almost impossible to get into the 20th century. There is presumably a vast century of work accessible to almost no one. And yet it will end up explaining the world because it always does.

Someone once said that in mathematics the answer often appears before the question. It seems to underlie the structure of everything, which is, I suppose, unsurprising since it is essentially the study of patterns abstracted from reality.

The other great thing about it is that there is no role play; and no one ever asks me, their voice pregnant with concern, how I feel about it.
Preclinical in vivo evaluation of a novel treatment strategy combining a Wee1 inhibitor with radiotherapy.
Authors: K. Mason, J. Pickett, C. Ware, H. Hirai, P. Strack, S. D. Shumway, K. Ang, T. A. Buchholz, L. Milas, C. A. Buser
Journal: Journal of Clinical Oncology (2010)

10596 Background: Wee1 regulates G2 checkpoint signaling by phosphorylating and inactivating cyclin-dependent kinase1 (Cdc2). Interference with this checkpoint is hypothesized to render p53 deficient cells, which lack a G1 checkpoint, more susceptible to DNA damaging agents by not allowing for sufficient DNA repair before entering mitosis. A novel Wee1 inhibitor (MK-1775) sensitized p53 deficient cells to in vitro cytotoxicity of gemcitabine, cisplatin, and carboplatin and increased in vivo antitumor effects (Mol Cancer Ther, 8:2992, 2009). The present study examined whether Wee1 inhibition improves radioresponse of human lung cancer models. Methods: Xenografts (p53 wild type [wt] A549, p53 mutant H1299 and p53 null Calu6) were generated in the leg of nude mice by i.m. injection of 1- 5 X 106 tumor cells grown in vitro. Tumors were measured twice weekly and treatments started at 8mm tumor diameter. Irradiation (IR) was given 24h before Wee1 inhibitor (gavage BID separated by 3h for 5 days). When fractionated (Fx) IR (2 or 5Gy for 5 days) was used, the 2nd-5th exposures were given 1h following the first dose of Wee1 inhibitor. Treatment endpoints included tumor growth delay (TGD), tumor cure (TCD50), and immunohistochemistry (IHC). Statisticalanalyses included Student's t-test for TGD and IHC and likelihood ratio test for TCD50. Results: Wee1 inhibition combined with single or Fx IR increased TGD of p53 deficient (but not p53 wt) tumors supra-additively. The best combination consisted of Fx IR combined with Wee1 inhibitor (Calu6 TGD enhancement factor [EF] 2.04, P 0.03). This schedule also improved curability of Calu6 by EF of 1.18 (Fx IR TCD50 41.2Gy reduced to 35Gy, P 0.05). Treatment was associated with rapid transient downregulation of pCDC2, upregulation of pChk1, pHH3 and γH2AX, and increased mitoses followed by mitotic catastrophe. Mechanistically, both cell cycle deregulation and inhibition of DNA repair likely contributed to the observed synergy. Conclusions: This novel Wee1 inhibitor (MK-1775) significantly enhanced IR response of p53 deficient human tumor xenografts in preclinical studies and shows high potential for translation to clinical trial(s) in combination with radiotherapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Merck
The Prognostic Role of Diabetes Mellitus for Cardiac Complications in a Large Cohort of Well Treated Thalassemia Major Patients
Authors: Antonella Meloni, Maria Rita Gamberini, Giuseppe Rossi, Francesco Sorrentino, Domenico Giuseppe D'Ascola, Anna Spasiano, Aldo Filosa, Liana Cuccia, Nicola Dello Iacono, Gianluca Forni, Vincenzo Caruso, Aurelio Maggio, Lorella Pitrolo, Angelo Peluso, Massimo Midiri, Massimiliano Missere, Maria Giovanna Neri, Alessia Pepe
Journal: Blood (2014)
OC-037 Epidemiology and resistance patterns of culture-positive spontaneous bacterial peritonitis in Leeds 2006–2008
Authors: J S R Jennings, D Greer, F Croxen, M Davies, J Sandoe
Journal: Gut (2010)

<h3>Introduction</h3> Spontaneous bacterial peritonitis (SBP) is a life threatening infection of ascitic fluid which occurs primarily in patients with pre-existing ascites in the setting of cirrhosis. Risk factors for developing SBP include: prior episode of SBP, gastrointestinal bleeding, ascitic total protein &lt;1.0 g/dl and Child-Pugh score.1 Causative microorganisms include members of the normal microbial flora of the gastrointestinal tract including <i>Escherichia coli</i> (70%), Klebsiella species (10%), Proteus species (4%), Enterococcus faecalis (4%) and Pseudomonas species (2%).1 The choice of antimicrobial therapy must take into consideration the increasing frequency of hospital acquired infections, such as <i>Clostridium difficile</i> infection. <h3>Aim</h3> To identify the local epidemiology and resistance patterns of culture-positive SBP. <h3>Methods</h3> We retrospectively assessed the culture results of all ascitic fluid samples that grew a single organism in Leeds during the 3 years 2006–2008. Patients case notes were assessed to establish a diagnosis of SBP. An ascitic fluid neutrophil count ≥ 250/mm<sup>3</sup> in patients with liver disease was used to confirm the diagnosis of SBP.12 We excluded culture-negative SBP. <h3>Results</h3> Single organism positive ascitic cultures were identifed in 42 patients with liver disease and an ascitic fluid neutrophil count ≥250/mm<sup>3</sup>. Mean age 52.1 years, 32/42 male. Underlying liver disease was ALD 35/42, HCV 3/42, PBC 1/42, NAFLD 1/42, Cryptogenic 1/42 and Post transplant 1/42. At the time of diagnosis of SBP the mean ascitic total white cell count 5.25, mean ascitic neutrophil count 4.08, mean serum Na+ 129.6 mmol/l and mean serum creatinine 147 mmol/l. Overall Child score A 0, B 8/42, C 34/42 and mean MELD score 24.1. The isolated organisms were <i>Escherichia coli</i> 15, Klebsiella spp. 7, other coliforms 10, Gram positive organisms 8 (including Enterococcus 2, Corynebacterium spp. 2). The Gram-negative isolates were resistant to a number of antibiotics: ciprofloxacin 38% (13/34), cefuroxime 29% (10/34), amoxycillin 32% (11/34) and tazocin 17% (6/34). The 30-day mortality was 50%. <h3>Conclusion</h3> Empirical treatment regimes need to take into account local resistance patterns. Ciprofloxacin has been widely used for treatment and prophylaxis in SBP. Resistance has now become a significant problem.