tbuckley/cabot-search huggingface dataset:
Resminostat in advanced hepatocellular carcinoma (HCC): Overall survival subgroup analysis of prognostic factors in the SHELTER trial.
Authors: Michael Bitzer, Tom M. Ganten, Marcus A. Woerns, Jens T. Siveke, Matthias M. Dollinger, Max E. Scheulen, Henning Wege, Edoardo G. Giannini, Umberto Cillo, Franco Trevisani, Armando Santoro, Vincenzo Montesarchio, Anna Mais, Bernhard Hauns, Julia Asche, Thomas Herz, Stefano Pegoraro, Aldo Ammendola, Stefan W. Henning, Bernd Hentsch
Journal: Journal of Clinical Oncology (2013)

e15088 Background: Previously published results of the phase I/II SHELTER study demonstrated efficacy and safety of the novel pan-HDAC inhibitor resminostat in second-line treatment of HCC patients (pts) who had progressed under first-line sorafenib. As patient baseline characteristics might influence treatment outcome, an analysis of their potential influence on overall survival (OS) was performed. Methods: 45 pts with advanced-stage HCC and centrally confirmed radiologic progression under first-line sorafenib were included in a multi-center, two-arm trial. Resminostat was administered either alone or in combination with sorafenib. A Cox proportional-hazards model was used to evaluate the interaction between baseline characteristics and the effect of the two treatment groups on overall survival. Results: In the combination group, pts with Child-Pugh-A, ECOG 0 or absence of vascular invasion had a statistically significant lower risk of death compared to pts with Child-Pugh-B (HR 0.19, 95% CI 0.06-0.55), ECOG 1 (HR 0.15, 95% CI 0.05-0.44), or vascular invasion (HR 0.37, 95% CI 0.15-0.93), respectively. For pts with BCLC-B there was a strong trend, although not statistically significant, of a lower risk of death when compared to pts with BCLC-C (HR 0.43, 95% CI 0.13-1.49). Etiology, prior TACE therapy, extrahepatic spread and interval between first- and second-line treatment had no impact on overall survival in this study. Similar findings were observed in the monotherapy group. Comparing the impact of these baseline characteristics in the combination and monotherapy group, no statistically significant different influence on OS between both treatment groups was observed. Conclusions: Resminostat in combination with sorafenib provides a substantial OS benefit (median OS of 8.1 months) for advanced HCC patients who had developed progressive tumor disease under first-line sorafenib therapy. Subgroup analysis of patient baseline characteristics revealed a significant influence of Child-Pugh index, ECOG classification, and vascular invasion on overall survival, whereas e.g. the interval between first- and second-line treatment had no impact on overall survival. Clinical trial information: NCT00943449.
Progression-free survival at 24 months (PFS24) and subsequent outcome for patients with diffuse large B-cell lymphoma (DLBCL) enrolled on randomized clinical trials
Authors: M.J. Maurer, T.M. Habermann, Q. Shi, N. Schmitz, D. Cunningham, M. Pfreundschuh, J.F. Seymour, U. Jaeger, C. Haioun, H. Tilly, H. Ghesquieres, F. Merli, M. Ziepert, R. Herbrecht, J. Flament, T. Fu, C.R. Flowers, B. Coiffier
Journal: Annals of Oncology (2018)

BackgroundPatients with diffuse large B-cell lymphoma treated with first-line anthracycline-based immunochemotherapy and remaining in remission at 2 years have excellent outcomes. This study assessed overall survival (OS) stratified by progression-free survival (PFS) at 24 months (PFS24) using individual patient data from patients with DLBCL enrolled in multi-center, international randomized clinical trials as part of the Surrogate Endpoint for Aggressive Lymphoma (SEAL) Collaboration.Patients and methodsPFS24 was defined as being alive and PFS24 after study entry. OS from PFS24 was defined as time from identified PFS24 status until death due to any cause. OS was compared with each patient's age-, sex-, and country-matched general population using expected survival and standardized mortality ratios (SMRs).ResultsA total of 5853 patients enrolled in trials in the SEAL database received rituximab as part of induction therapy and were included in this analysis. The median age was 62 years (range 18–92), and 56% were greater than 60 years of age. At a median follow-up of 4.4 years, 1337 patients (23%) had disease progression, 1489 (25%) had died, and 5101 had sufficient follow-up to evaluate PFS24. A total of 1423 assessable patients failed to achieve PFS24 with a median OS of 7.2 months (95% CI 6.8–8.1) after progression; 5-year OS after progression was 19% and SMR was 32.1 (95% CI 30.0–34.4). A total of 3678 patients achieved PFS24; SMR after achieving PFS24 was 1.22 (95% CI 1.09–1.37). The observed OS versus expected OS at 3, 5, and 7 years after achieving PFS24 was 93.1% versus 94.4%, 87.6% versus 89.5%, and 80.0% versus 83.7%, respectively.ConclusionPatients treated with rituximab containing anthracycline-based immunochemotherapy on clinical trials who are alive without progression at 24 months from the onset of initial therapy have excellent outcomes with survival that is marginally lower but clinically indistinguishable from the age-, sex-, and country-matched background population for 7 years after achieving PFS24.
SAT0334 Clinical and sonographic analysis of psoriasis patients without musculoskeletal complaints. preeliminary results of a prospective study: the pre-aps cohort
Authors: J. Ramírez García, A. Cuervo, M. Alsina, R. Celis, V. Ruiz-Esquide, R. Castellanos, M.V. Hernández, R. Sanmarti, J.D. Cañete
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Early diagnosis in psoriatic arthritis (PsA) is mandatory in order to initiate early therapy and prevent disability. Around 20% of patients with Psoriasis (PsO) routinely visited in Dermatology departments have PsA previously undiagnosed. <h3>Objectives</h3> The aim of this study is to evaluate the presence of inflammation by clinical examination and ultrasound in joints and enthesis of patients with PsO without musculoskeletal symptoms. <h3>Methods</h3> Patients with PsO under topic or PUVA therapy without musculoskeletal symptoms were referred to our Arhritis Unit. Clinical and demographic data were collected. The patients were evaluated for Body Surface Area (BSA), Swollen Joint Count (SJC) (66 joints), Tender Joint Count (TJC) (68 joints) and enthesis (MASES). Psoriatic Arthritis Impact of Disease tool questionnaire (PsAID) and Psoriasis Epidemiology Screening tool questionnaire (PEST) were used to assess the impact of the disease. A comprehensive ultrasound evaluation of 46 joints and 12 enthesis was made (ESAOTE MylabTwice, 12–18 Mhz probe). Enthesis score was calculated using the Madrid Sonographic Enthesis Index (MASEI) and a total score for synovitis (synovial hypertrophy and Power Doppler) was also calculated. <h3>Results</h3> 42 patients were included. 20 patients were female (48%), mean age (SD) was 48.3 y (14.6) and disease duration was 17.9 y (15.9). Mean BMI was 24.6 (5.2) and BSA 5 (8.7). 13 out of 42 (31%) had severe PsO (systemic treatment or BSA &gt;10% at any time of evolution). 4 patients (9.5%) had Power Doppler signal and 2 (4.8%) fulfilled criteria for ultrasound-defined active synovitis (SH ≥2 + PD) despite no signs or symptoms of musculoskeletal disease. However, although structural alterations such as calcifications and enthesophytes were frequent, no PD was found at any enthesis. In the univariate analysis, higher BMI (p=0.013), weight (p=0.010), waist (p=0.033) and hip (p=0.014) circumferences were significantly associated with severe PsO. In the same way, CRP serum levels were also significantly higher in patients with severe PsO (p=0.027). A strong trend was found between higher MASEI scores and onycopathy (p=0.09). pan&gt; <h3>Conclusions</h3> Patients with PsO under topic or PUVA therapy without musculoskeletal sympoms have a low prevalence of findings in the joints and enthesis ultrasound evaluation. Of note, 9.5% of PsO patients had subclinical synovitis defined as PD. No changes in those finding were found in a short follow-up (6 months) in these patients. A higher number of patients would be necessary to have strong results. These patients will be followed in order to confirm if they develop Psoriatic Arthritis. <h3>Acknowledgements</h3> This work was partially financed by Pfizer-Spain <h3>Disclosure of Interest</h3> None declared
Frailty and pre-frailty in middle-aged and older adults and its association with multimorbidity and mortality: a prospective analysis of 493 737 UK Biobank participants
Authors: Peter Hanlon, Barbara I Nicholl, Bhautesh Dinesh Jani, Duncan Lee, Ross McQueenie, Frances S Mair
Journal: The Lancet Public Health (2018)

Frailty is associated with older age and multimorbidity (two or more long-term conditions); however, little is known about its prevalence or effects on mortality in younger populations. This paper aims to examine the association between frailty, multimorbidity, specific long-term conditions, and mortality in a middle-aged and older aged population.Data were sourced from the UK Biobank. Frailty phenotype was based on five criteria (weight loss, exhaustion, grip strength, low physical activity, slow walking pace). Participants were deemed frail if they met at least three criteria, pre-frail if they fulfilled one or two criteria, and not frail if no criteria were met. Sociodemographic characteristics and long-term conditions were examined. The outcome was all-cause mortality, which was measured at a median of 7 years follow-up. Multinomial logistic regression compared sociodemographic characteristics and long-term conditions of frail or pre-frail participants with non-frail participants. Cox proportional hazards models examined associations between frailty or pre-frailty and mortality. Results were stratified by age group (37-45, 45-55, 55-65, 65-73 years) and sex, and were adjusted for multimorbidity count, socioeconomic status, body-mass index, smoking status, and alcohol use.493 737 participants aged 37-73 years were included in the study, of whom 16 538 (3%) were considered frail, 185 360 (38%) pre-frail, and 291 839 (59%) not frail. Frailty was significantly associated with multimorbidity (prevalence 18% [4435/25 338] in those with four or more long-term conditions; odds ratio [OR] 27·1, 95% CI 25·3-29·1) socioeconomic deprivation, smoking, obesity, and infrequent alcohol consumption. The top five long-term conditions associated with frailty were multiple sclerosis (OR 15·3; 99·75% CI 12·8-18·2); chronic fatigue syndrome (12·9; 11·1-15·0); chronic obstructive pulmonary disease (5·6; 5·2-6·1); connective tissue disease (5·4; 5·0-5·8); and diabetes (5·0; 4·7-5·2). Pre-frailty and frailty were significantly associated with mortality for all age strata in men and women (except in women aged 37-45 years) after adjustment for confounders.Efforts to identify, manage, and prevent frailty should include middle-aged individuals with multimorbidity, in whom frailty is significantly associated with mortality, even after adjustment for number of long-term conditions, sociodemographics, and lifestyle. Research, clinical guidelines, and health-care services must shift focus from single conditions to the requirements of increasingly complex patient populations.CSO Catalyst Grant and National Health Service Research for Scotland Career Research Fellowship.
Making progress on the global crisis of obesity and weight management
Authors: Michael E J Lean, Arne Astrup, Susan B Roberts
Journal: BMJ (2018)

Food and obesity are undoubtedly linked but the relation is complex. Michael Lean and colleagues discuss what we know, and what we don't know, about weight management Obesity is an unsolved crisis, generating long term distress and disabilities, reducing human capital, and increasing disease burdens and healthcare costs globally. Obesity has a complex aetiology, incurring controversies within both scientific and media arenas.1 Poor education and socioeconomic situations are important drivers of severe obesity, confounding country analyses by racial or ethnic groups. Data collected by EUROSTAT show wide variations in prevalences of people with a body mass index (BMI) >30 across European states.2 Age is important: by age 65-70, as many as 40% of all people in the UK reach a BMI >30, and 80% have a BMI >25.3 Many with BMI >30 will experience secondary medical consequences, although overall life expectancies of populations have increased steadily despite obesity and the disabilities it brings. Many factors have been associated with weight gain, difficulty achieving and maintaining weight loss, and secondary medical consequences of obesity. Some have causal influences, many are innocent bystanders, and some have no basis in science. We focus on those related to food. The energy equation—that calories consumed=calories expended +/- calories stored (as body fat or glycogen)—is always true. Obesity develops if absorbed dietary energy (calories) from foods exceeds energy expenditure for a considerable period (box 1). Similarly, excess body fat is lost if energy intake falls below expenditure. However, numerous multilevel factors contribute to determining energy expenditure, intake, and absorption, and small mismatches with food consumption over a long period can lead to large cumulative weight changes. Box 1 ### Energy balance explained Each kg of adipose tissue contains about 7000 kcal. Thus consuming just 100 kcal a day more than energy expenditure for a year could result in a … RETURN TO TEXT
Race as a risk factor for developing osteonecrosis of the jaw after long term bisphosphonate therapy in patients with metastatic breast cancer
Authors: T. Aiti, S. McDunn, L. Hussein, I. Ashkenazi, A. Jajeh, Y. Wang, H. A. Zaren
Journal: Journal of Clinical Oncology (2006)

596 Background: Association between osteonecrosis of the jaw (ONJ) and bisphosphonate treatment has been increasingly reported in the literature. Methods: This is a retrospective review of a single institution’s experience with patients diagnosed with bone metastasis secondary to breast cancer, who developed ONJ while treated with bisphosphonates (Zoledronic acid - Zometa; Pamidronate - Aredia), between 1.1.2001 and 10.30.2005. Presentation, age, race, and outcome were reviewed. Logistic Regression was used to test for statistical significance. Results: 161 patients with bone metastasis secondary to breast cancer treated with bisphosphonates were reviewed (82 African American, 29 Caucasians, 26 Hispanic, 15 Asian and 9 others.). ONJ developed in 6 (3.7%) patients, 5 of which were Caucasians. Logistic regression adjusting for dose shows that the odds ratio for developing ONJ comparing Caucasians with non-Caucasians is 45.7 (p=0.016). Age did not impact occurrence of ONJ. All 6 patients developed ONJ after a minimum of 31 months of treatment. Two patients had a history of previous tooth extraction. In four other patients, ONJ appeared spontaneously. One patient, who presented with an abscess, developed sepsis which resulted in the patient’s death. Two patients were treated with debridement and antibiotics and their lesions healed. Three other patients ended up suffering from a chronically exposed bone. Conclusion: ONJ is a serious complication of bisphosphonate therapy and it affected a significant proportion of our patients. Our data suggests that Caucasians may be more susceptible. Since sample size is small, determining if race is a risk factor for the development of ONJ, while on bisphosphonate therapy, will require further investigation. No significant financial relationships to disclose.
FRI0067 Trends in the incidence of felty’s syndrome in patients with rheumatoid arthritis in spain: an observational cohort study of hospital discharges from 1999 to 2015 (TREND-AR STUDY)
Authors: J.L. Morell, R. Mazzucchelli, E. Perez Fernandez, J. Quiros, C. Macia Villa, N. Crespi, M. Peña, C. Barbadillo, M. Espinosa, H. Godoy, M. Fernandez-Prada, M. Galindo, A. Garcia Vadillo, O. Guzon Illescas, A. Herranz, C. Martinez Prada, C. Morado Qiñoa, V. Villaverde
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Felty’s syndrome (FS) is an unfrequent entity realted to Rheumatoid Arthritis (RA) but it’s unknown the trend of FS in Spain. <h3>Objectives</h3> To analyse the incidence and trend of hospital admissions for FS in RA patients in Spain from 1999 to 2015. <h3>Methods</h3> We performed an observational retrospective population study analysing the spanish administrative database that includes a Minimun Basic Data Set (MBDS) of hospital admissions of RA patients from 1999 to 2015. We selected the MBDSs for FS. Cases were identified by the presence in primary and secondary diagnosis of its ICD9 code. The population at risk was estimated with an estimated prevalence of RA of 0,5% (0,8% women and 0,2% men). Crude and adjusted rates were calculated, and the trend was analysed using the Generalised Linear Model (GLM) with the year as the analysis variable. SPSS version 20 (SPSS Inc, Chicago, IL) was used. <h3>Results</h3> 338.343 RA hospital admissions were detected, being 802 (0,2%) due to FS, 455 (56,7%) women and 347 (43,3%) men. Mean age was 67,94(SD 13,76). There were 61 (7,6%) deaths. Age-adjusted rate during the period was 42,19/10<sup>5</sup> inhab. per year (19,76 women and 64,61 men). FS age-adjusted rate decreased from 25,90/10<sup>5</sup> inhab. per year in 1999 to 17,20 in 2015, both women (12,85 in 1999 to 11,75 in 2015) and men (80,15 in 1999 to 38,75 in 2015). An annual decrease in the FS rate of 0,5% is estimated (RRI 0,995; CI 95% 0,976–1,014). <h3>Conclusions</h3> In Spain FS hospital admissions in patients with RA decreased between 1999–2015 with an estimation of 0,5% annual reduction not statistically significative. <h3>Disclosure of Interest</h3> None declared
A Randomized Controlled Trial Comparing Efficacy and Safety of Insulin Glargine 300 Units/mL Versus 100 Units/mL in Older People With Type 2 Diabetes: Results From the SENIOR Study
Authors: Robert Ritzel, Stewart B. Harris, Helen Baron, Hermes Florez, Ronan Roussel, Melanie Espinasse, Isabel Muehlen-Bartmer, Nianxian Zhang, Monica Bertolini, Claire Brulle-Wohlhueter, Medha Munshi, Geremia B. Bolli
Journal: Diabetes Care (2018)

SENIOR compared the efficacy and safety of insulin glargine 300 units/mL (Gla-300) with glargine 100 units/mL (Gla-100) in older people (≥65 years old) with type 2 diabetes.SENIOR was an open-label, two-arm, parallel-group, multicenter phase 3b trial designed to enroll ∼20% of participants aged ≥75 years. Participants were randomized 1:1 to Gla-300 or Gla-100, titrated to a fasting self-monitored plasma glucose of 5.0-7.2 mmol/L (90-130 mg/dL).In total, 1,014 participants were randomized (mean age: 71 years). Comparable reductions in HbA1c were observed from baseline to week 26 for Gla-300 (-0.89%) and Gla-100 (-0.91%) in the overall population (least squares mean difference: 0.02% [95% CI -0.092 to 0.129]) and for participants aged ≥75 years (-0.11% [-0.330 to 0.106]). Incidence and rates of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycemia events were low and similar between both treatment groups, with lower rates of documented symptomatic hypoglycemia with Gla-300. The lower risk of hypoglycemia with Gla-300 versus Gla-100 was more apparent in the subgroup aged ≥75 years versus the overall population. Significantly lower annualized rates of documented symptomatic (≤3.9 mmol/L [≤70 mg/dL]) hypoglycemia were observed (Gla-300: 1.12; Gla-100: 2.71; rate ratio: 0.45 [95% CI 0.25-0.83]).Efficacy and safety of Gla-300 was demonstrated in older people (≥65 years of age) with type 2 diabetes, with comparable reductions in HbA1c and similarly low or lower risk of documented symptomatic hypoglycemia versus Gla-100. A significant benefit in hypoglycemia reduction was seen in participants aged ≥75 years.
Acute cholangitis complicating a chronic alveolar echinococcosis: an unusual therapeutic cholangioscopy
Authors: Jean-Phillip Le Mouel, Mathurin Fumery, Sami Hakim, Henri Thiebault, Franck Brazier, Eric Nguyen-Khac, Richard Delcenserie
Journal: Endoscopy (2018)

A 71-year-old man with a history of chronic alveolar echinococcosis presented with acute cholangitis and severe sepsis. Echinococcosis had been diagnosed 38 years previously. At this time, a left hepatectomy, associated with distal gastrectomy and gastro-jejunal anastomosis (Finsterer) was performed. Afterwards, despite parasitostatic therapy, the infection progressed slowly with chronic biliary compression, causing secondary biliary cirrhosis and episodes of recurrent acute cholangitis. Several endoscopic retrograde cholangiopancreatographies (ERCPs) with insertion of biliary plastic stents had been performed in another hospital.
FRI0513 The impact of depression, anxiety and fatigue in patients with behÇet’s disease
Authors: S. Can Sandikci, S. Colak, A. Omma, M.E. Enecik
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Behçet's disease (BD) is a type of systemic vasculitis and inflammatory disease with unknown etiology which is associated with fatigue and lower quality of life (QoL).<sup>1</sup> <h3>Objectives</h3> In this study we aimed to assess the relationship between BDCAF and BDQoL, depression, anxiety and fatigue in Behçet's disease. <h3>Methods</h3> This is a cross-sectional study of 155 Behcet's syndrome (BS) patients and 107 healthy controls in Turkey. All subjects completed the Multidimensional Assessment of Fatigue (MAF) questionnaire, Hospital Anxiety and Depression (HADS) scale. Disease activity among BS patients was assessed using the Behçet's Disease Current Activity Form (BDCAF), and the physician's global assessment (PGA). And BD patients completed the Behçet's Disease Quality of Life (BDQoL) questionnaire. <h3>Results</h3> There was no significant difference with age and gender between the groups. BS patients had significantly higher HADS-anxiety (HADS-A), HADS-depression (HADS-D) and MAF scores than the healthy controls (p&lt;0.05) (table 1). BS patients with active disease had significantly higher MAF and HADS-A scores compared to inactive BS patients (p&lt;0.05). MAF scores showed positive correlations with HADS-A, HADS-D, BDCAF and BDQoL (table 2). <h3>Conclusions</h3> Fatigue and anxiety is common in clinically active BS patients compared with healthy controls and inactive BD patients. <h3>Reference</h3> [1] Tascilar NF, Tekin NS, Ankarali H, et al. Sleep disorders in Behcet's disease, and their relationship with fatigue and quality of life. J Sleep Res2012;21(3):281–288. <h3>Disclosure of Interest</h3> None declared
Autopsy 2018
Authors: Lee Goldman
Journal: Circulation (2018)

he average autopsy rate in US hospitals was ≈50% in the 1940s and 41% in 1970, just before the Joint Commission on the Accreditation of Hospitals eliminated the requirement for a 20% autopsy rate.Since that time, autopsy rates have been in free fall, with estimated rates currently ≈8% overall, including forensic cases, but only 4% among in-hospital deaths.About 700 000 Americans die in acute-care hospitals each year, so these percentages translate into ≈28 000 hospital autopsies annually.Three explanations are commonly proposed for these falling rates: the lack of reimbursement for autopsies, the fear of disclosing mistakes that would lead to malpractice suits, and the belief that advances in medical technology, including but not limited to computed tomographic scans and magnetic resonance imaging, have made autopsies obsolete.The first 2 rationales could easily be resolved by effective legislation, such as Medicare reimbursement for autopsies, or regulation, such as reinstatement of a minimum required autopsy rate.From a scientific perspective, however, the key issue is whether autopsies remain as critical for measuring the quality of care and advancing medicine as they were 80 or even 50 years ago.