bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma cholesterol and lipoprotein levels in relation to tumor aggressiveness and survival in HCC patients
Authors: Carr Brian I. , Giannelli Gianluigi , Guerra Vito , Giannini Edoardo G , Farinati Fabio , Rapaccini Gian Ludovico , Marco Maria Di , Zoli Marco , Caturelli Eugenio , Masotto Alberto , Virdone Roberto , Sacco Rodolfo , Trevisani Franco 
Published: June 2018

Background and Aims: Hepatocellular carcinoma is associated with several chronic liver diseases, especially chronic hepatitis B virus, hepatitis C virus, and alcoholism. It is increasingly appreciated that obesity/metabolic syndrome is also associated with chronic liver disease and subsequent hepatocellular carcinoma. Methods: We retrospectively investigated the serum lipid profiles in a large hepatocellular carcinoma cohort, associated predominantly with the hepatitis B virus, hepatitis C virus, alcohol or nonalcoholic steatohepatitis. The cohort was examined both as a whole, as well as stratified by etiology. Results: We found significant associations between parameters of hepatocellular carcinoma biology such as maximum tumor diameter, portal vein thrombosis, tumor multifocality or alpha-fetoprotein levels and individual lipid components, including total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides and body mass index. In a final multiple linear regression model considering all lipid variables together, only high-density lipoprotein cholesterol was significantly associated with the tumor Tumor Aggressiveness Index. High-density lipoprotein cholesterol was found to have a statistically higher hazard ratio for death than low high-density lipoprotein cholesterol levels (Cox). On examination by etiological group, alpha-fetoprotein levels were significantly higher in patients with hepatitis C virus compared to those with alcohol or nonalcoholic steatohepatitis, but maximum tumor diameter, tumor multifocality and portal vein thrombosis were similar across etiological groups. Nonalcoholic steatohepatitis patients had significantly less cirrhosis than other groups and hepatitis B virus patients had significantly higher cholesterol and low-density lipoprotein cholesterol levels than hepatitis C virus patients. Conclusions: This is the first report, to our knowledge, of a relationship between serum lipid parameters and indices of hepatocellular carcinoma growth, invasion and aggressiveness, as well as with survival.
Prognostic implications of hepatitis B virus infection in intrahepatic cholangiocarcinoma treated with first-line gemcitabine plus cisplatin
Authors: Chae Heejung , Cho Hyungwoo , Yoo Changhoon , Kim Kyu-pyo , Jeong Jae Ho , Chang Heung-Moon , Kang Jihoon , Lee Han Chu , Lim Young-Suk , Kim Kang Mo , Shim Ju Hyun , Lee Sang Soo , Park Do Hyun , Song Tae Jun , Hwang Shin , Song Gi-Won , Moon Deok-Bog , Lee Young-Joo , Lee Jae Hoon , Ryoo Baek-Yeol 
Published: June 2018

Purpose: Hepatitis B virus infection is a well-known risk factor for intrahepatic cholangiocarcinoma. However, its prognostic impact has rarely been investigated in advanced intrahepatic cholangiocarcinoma. Methods: Between April 2010 and May 2015, 296 patients with unresectable or metastatic intrahepatic cholangiocarcinoma who received gemcitabine plus cisplatin (GemCis) were categorized into a hepatitis B virus group (n=62; 21%) and a non-hepatitis B virus group (n=234; 79%). Clinicopathological features and survival outcomes were retrospectively reviewed and analyzed. Results: The median age of patients was 59 years (range, 27–78). The median overall survival with first-line GemCis was 9.4 months (95% CI 8.4, 10.4). Compared to the non-hepatitis B virus group, the hepatitis B virus group was younger (median age, 57 vs. 61 years, P = 0.001), mainly male (74% vs. 57%, P = 0.02), and had lower frequency of elevated cancer antigen (CA) 19-9 (34% vs. 59%, P = 0.001) and alkaline phosphatase (43% vs. 61%, P = 0.01). In a univariate analysis, the hepatitis B virus infection showed a marginal relationship with poor overall survival compared to the non-hepatitis B virus infection (median, 8.3 vs. 10.0 months; P=0.13). A multivariate analysis of potential prognostic factors revealed a significant association with poor overall survival in the hepatitis B virus group (hazard ratio (HR) =1.50, P = 0.02). Initial metastatic disease (vs. recurrent/unresectable disease; HR=1.50), metastatic sites ⩾ 2 (vs. 0–1; HR=1.51), Eastern Cooperative Oncology Group performance status ⩾ 2 (vs. 0–1; HR=1.93), elevated total bilirubin (vs. normal; HR=1.83), and low albumin (vs. normal; HR=1.52) were significantly related to an unfavorable overall survival. Conclusions: This study suggests that the hepatitis B virus infection may be associated with distinctive clinicopathological characteristics and poor outcome in advanced intrahepatic cholangiocarcinoma treated with GemCis.
Morphometric changes over the whole brain in caffeine-containing combination-analgesic-overuse headache
Authors: Chen Xiaoyan , Chen Zhiye , Dong Zhao , Liu Mengqi , Yu Shengyuan 
Published: June 2018

Objective To investigate brain morphometric changes in medication-overuse headache with excessive intake of caffeine-containing combination analgesics. Materials and methods We recruited 32 medication-overuse headache patients overusing caffeine-containing combination analgesics and 26 normal controls with matched sex and age. Magnetic resonance T1-weighted images were processed by automatic volume algorithm of brain regions over the whole brain according to the neuromorphometrics template. We explored the volume differences between groups and correlation with clinical variables. Results Medication-overuse headache patients demonstrated decreased volume in cerebellum, optic chiasm, and increased volume in right lateral orbital gyrus, left calcarine, bilateral middle occipital gyrus, right superior parietal lobe, and right temporal transverse gyrus compared with normal controls. The increased volume was primarily contributed by patients of lower headache frequency (10–20 days/month) and with no psychological comorbidities. In regression analyses, the volume of bilateral middle occipital gyrus had negative association with migraine duration, and the volume of right lateral orbital gyrus and right superior parietal lobe was negatively correlated with number of medications per month. Conclusions Volume changes of brain regions involved in affective and cognitive processing, visual and auditory perception, and pain sensory/discrimination suggested a particular role of those regions in the pathogenesis of medication-overuse headache overusing caffeine-containing combination analgesics. Morphometric changes in multiple visual processing areas and volume gain in lower headache frequency and less anxiety and depression may be specific features related to overusing caffeine-containing combination analgesics.
Capitate osteotomy and transposition for type III Kienböck’s disease
Authors: Li Jianbing , Pan Zhijun , Zhao Yunzhen , Hu Xinlei , Zhao Xiang 
Published: June 2018

The aim of this study was to assess the results of capitate osteotomy and transposition for stage III Kienböck’s disease. Capitate osteotomy and transposition combined with an autologous iliac bone graft was carried out in 17 patients. At the final follow-up for a mean of 68 months (range 16–127 months) after surgery, the mean visual analogue scale score was 0.6 (range 0–5). The mean Wrightington wrist function score was 8. The mean grip strength was 79% of the unaffected side. There were 16 satisfactory results. The one unsatisfactory result occurred in a woman who developed a nonunion of the osteotomy. There were no other complications of the surgery. Our results show that capitate osteotomy and transposition is a simple and reliable method for the management of stage III Kienböck’s disease. Level of evidence: IV
Ensuring Capability to Provide Safe Patient Care Prior to Occupying Renovated Clinical Area
Authors: West Gordon F. , Rose Traceee J. 
Published: June 2018

Objective: To determine the effectiveness of simulation in improving staff confidence to provide safe patient care in a new or unfamiliar patient care area. Background: Hospitals undergo constant renovation to meet the needs of the populations they serve. Relocating to a newly renovated care area can potentially impact patient safety through workflow process changes. Method: Simulated patient care scenarios were used to assess functionality of equipment and staff orientation to a newly renovated ward. Additionally, staff confidence to provide safe patient care was assessed prior to patient relocation. Results: All participating staff reported feeling confident in their ability to provide safe patient care within the newly renovated ward at the conclusion of the exercise. Conclusions: In this case study, the use of simulated patient care scenarios was successful to orientate staff to a new clinical space. Additionally, staff were able to identify workflow changes and access the functionality of newly installed equipment. This exercise allowed staff to gain confidence in their ability to provide safe patient care in a newly renovated area.
Immunological corollary of the pulmonary mycobiome in bronchiectasis: the CAMEB study
Authors: Mac Aogáin Micheál , Chandrasekaran Ravishankar , Lim Albert Yick Hou , Low Teck Boon , Tan Gan Liang , Hassan Tidi , Ong Thun How , Hui Qi Ng Amanda , Bertrand Denis , Koh Jia Yu , Pang Sze Lei , Lee Zi Yang , Gwee Xiao Wei , Martinus Christopher , Sio Yang Yie , Matta Sri Anusha , Chew Fook Tim , Keir Holly R. , Connolly John E. , Abisheganaden John Arputhan , Koh Mariko Siyue , Nagarajan Niranjan , Chalmers James D. , Chotirmall Sanjay H. 
Published: June 2018

Understanding the composition and clinical importance of the fungal mycobiome was recently identified as a key topic in a “research priorities” consensus statement for bronchiectasis.Patients were recruited as part of the CAMEB study: an international multicentre cross-sectional Cohort of Asian and Matched European Bronchiectasis patients. The mycobiome was determined in 238 patients by targeted amplicon shotgun sequencing of the 18S–28S rRNA internally transcribed spacer regions ITS1 and ITS2. Specific quantitative PCR for detection of and conidial quantification for a range of airwayAspergillusspecies was performed. Sputum galactomannan,Aspergillusspecific IgE, IgG and TARC (thymus and activation regulated chemokine) levels were measured systemically and associated to clinical outcomes.The bronchiectasis mycobiome is distinct and characterised by specific fungal genera, includingAspergillus,CryptococcusandClavispora.Aspergillus fumigatus(in Singapore/Kuala Lumpur) andAspergillus terreus(in Dundee) dominated profiles, the latter associating with exacerbations. High frequencies ofAspergillus-associated disease including sensitisation and allergic bronchopulmonary aspergillosis were detected. Each revealed distinct mycobiome profiles, and associated with more severe disease, poorer pulmonary function and increased exacerbations.The pulmonary mycobiome is of clinical relevance in bronchiectasis. Screening forAspergillus-associated disease should be considered even in apparently stable patients.
Maternal age at delivery, lung function and asthma in offspring: a population-based survey
Authors: Gómez Real Francisco , Burgess John A. , Villani Simona , Dratva Julia , Heinrich Joachim , Janson Christer , Jarvis Debbie , Koplin Jennifer , Leynaert Bénédicte , Lodge Caroline , Lærum Birger N. , Matheson Melanie C. , Norbäck Dan , Omenaas Ernst R. , Skulstad Svein M. , Sunyer Jordi , Dharmage Shyamali C. , Svanes Cecilie 
Published: June 2018

There is limited information about potential impact of maternal age on the respiratory health of offspring. We investigated the association of maternal age at delivery with adult offspring's lung function, respiratory symptoms and asthma, and potential differences according to offspring sex.10 692 adults from 13 countries participating in the European Community Respiratory Health Survey (ECRHS) II responded to standardised interviews and provided lung function measurements and serum for IgE measurements at age 25–55 years. In logistic and linear multilevel mixed models we adjusted for participants’ characteristics (age, education, centre, number of older siblings) and maternal characteristics (smoking in pregnancy, education) while investigating for differential effects by sex. Maternal age was validated in a subsample using data from the Norwegian birth registry.Increasing maternal age was associated with increasing forced expiratory volume in 1 s (2.33 mL per year, 95% CI 0.34–4.32 mL per year), more consistent in females (ptrend0.025) than in males (ptrend0.14). Asthma (OR 0.85, 95% CI 0.79–0.92) and respiratory symptoms (OR 0.87, 95% CI 0.82–0.92) decreased with increasing maternal age (per 5 years) in females, but not in males (pinteraction0.05 and 0.001, respectively). The results were consistent across centres and not explained by confounding factors.Maternal ageing was related to higher adult lung function and less asthma/symptoms in females. Biological characteristics in offspring related to maternal ageing are plausible and need further investigation.
Precision medicine: Clinical outcomes including long-term survival according to the pathway targeted and treatment period–The IMPACT study.
Authors: Tsimberidou Apostolia Maria , Hong David S. , Wheler Jennifer J. , Falchook Gerald Steven , Naing Aung , Fu Siqing , Piha-Paul Sarina Anne , Janku Filip , Cartwright Carrie , Broaddus Russell , Nogueras-Gonzalez Graciela M. , Hwu Patrick , Kurzrock Razelle 
Published: June 2018

LBA2553 Background: We evaluated the impact of pathway targeted and long-term follow-up of patients (pts) with refractory cancers referred to phase I trials. Methods: Pts referred to our program (2007-2013) had CLIA molecular testing. Pts treated with matched targeted therapy (MTT) vs. non-matched therapy (NMT) were analyzed. Results: Of 3,743 pts who had testing, 1,307 had ≥1 alteration and received therapy (MTT 711, NMT 596): med. age 57 yrs, range 16-86; 39% men; med. no. of prior therapies 4, range 0-16. The most common tumors were gastrointestinal 24.2%, gynecologic 19.4%, breast 13.5%, melanoma 11.9%, and lung 8.7%. Targeting MEK/RAF and RET pathways correlated with higher rates of CR/PR/SD≥6 months (mos), PFS and OS compared to others (all P < .001) (Table). Plateau was noted in OS (start, 38 mos): 74 of 711 (10.4%) in the MTT (max 10.7+ yrs) vs. 24 of 596 (4%) in the NMT (max 6 yrs) group were alive (p < .0001). In the MTT group, factors predicting longer PFS were non-PI3K pathway MTT (p < .001), no liver metastases (p < .001), PS < 2 (p = .006), normal LDH (p < .001) and albumin (p = .01) levels, and non-single agent therapy (p = .02). Factors predicting longer OS were non-PI3K pathway MTT (p < .001), no liver metastases (p < .001), PS < 2 (p < .001), normal LDH (p < .001) and albumin (p = .001) levels, and normal PLT counts (p = .03). Conclusions: Outcomes were superior in pts matched to RET and MEK/RAF inhibitors. Factors predicting longer PFS and OS were identified. In the MTT group, 10.4% of patients had OS ≥ 38 mos, the plateau starting point. Clinical trial information: NCT00851032. [Table: see text]
A UNICANCER phase III trial of hyperthermic intra-peritoneal chemotherapy (HIPEC) for colorectal peritoneal carcinomatosis (PC): PRODIGE 7.
Authors: Quenet François , Elias Dominique , Roca Lise , Goere Diane , Ghouti Laurent , Pocard Marc , Facy Olivier , Arvieux Catherine , Lorimier Gerard , Pezet Denis , Marchal Frederic , Loi Valeria , Meeus Pierre , De Forges Hélène , Stanbury Trevor , Paineau Jacques , Glehen Olivier ,   UNICANCER-GI Group and the French BIG-Renape Group
Published: June 2018

LBA3503 Background: Promising results have been obtained during the last decade using cytoreductive surgery (CRS) plus HIPEC for selected patients with colorectal PC who are amenable to complete macroscopic resection. This is the first trial to evaluate the specific role of HIPEC, after CRS, for the treatment of PC of colorectal origin. Methods: Prodige 7 is a randomized phase III, multicenter trial. Patients with histologically proven and isolated PC, peritoneal cancer index (PCI) ≤25 were eligible. Randomization (1:1) was stratified by center, complete macroscopic resection (R0/1 vs R2), and neoadjuvant systemic chemotherapy. Patients were treated with CRS plus HIPEC with oxaliplatin or CRS alone, in association with systemic chemotherapy. The primary endpoint was the overall survival (OS). Secondary endpoints were relapse-free survival (RFS) and toxicity. 264 patients were required to show a gain in median OS from 30 to 48 months (HR = 0.625) with a two-sided α = 0,046 and 80% power. Results: 265 patients from 17 centers were included between February 2008 and January 2014: 132 in Arm without HIPEC and 133 in Arm with HIPEC. The median age was 60 years (range: 30-74). Baseline characteristics were well balanced. The overall post-operative mortality rate was 1.5% and was not different between the two arms. The morbidity rates did not differ statistically at 30 days. At 60 days, the grade 3-5 morbidity rate was significantly higher with HIPEC (24.1% vs. 13.6%, p= 0.030). After a median follow up of 63.8 months (95% CI: 58.9-69.8), the median OS was 41.2 months (95% CI 35.1-49.7) in the non-HIPEC Arm and 41.7 months (95% CI: 36.2-52.8) in the HIPEC Arm, HR = 1.00 (95% CI: 0.73-1.37) p = 0.995. The median RFS was 11.1 months (95% CI: 9-12.7) in non-HIPEC Arm and 13.1 months (95% CI: 12.1-15.7) in HIPEC Arm, HR = 0.90 (95% CI: 0.69-1.90) (p = 0.486), whilst the 1-year RFS rates were 46.1% in non-HIPEC Arm and 59 % in the HIPEC Arm. Conclusions: The therapeutic curative management of PC from colorectal cancer by CRS shows satisfactory survival results. While the addition of HIPEC with oxaliplatin does not influence the OS. Clinical trial information: NCT00769405.
Pembrolizumab (pembro) versus platinum-based chemotherapy (chemo) as first-line therapy for advanced/metastatic NSCLC with a PD-L1 tumor proportion score (TPS) ≥ 1%: Open-label, phase 3 KEYNOTE-042 study.
Authors: Lopes Gilberto , Wu Yi-Long , Kudaba Iveta , Kowalski Dariusz , Cho Byoung Chul , Castro Gilberto , Srimuninnimit Vichien , Bondarenko Igor , Kubota Kaoru , Lubiniecki Gregory M. , Zhang Jin , Kush Debra A. , Mok Tony 
Published: June 2018

LBA4 Background: In KEYNOTE-024, pembro significantly improved PFS (primary end point) and OS (secondary end-point) over chemo as first-line therapy for metastatic NSCLC without targetable alterations and PD-L1 TPS ≥50%. In KEYNOTE-042, we compared pembro with chemo at the lower TPS of ≥1% (NCT02220894). Methods: Eligible patients (pts) were randomized 1:1 to ≤35 cycles of pembro 200 mg Q3W or investigator’s choice of ≤6 cycles of paclitaxel + carboplatin or pemetrexed (peme) + carboplatin with optional peme maintenance (nonsquamous only). Randomization was stratified by region (east Asia vs non-east Asia), ECOG PS (0 vs 1), histology (squamous vs nonsquamous), and TPS (≥50% vs 1-49%). Primary end-points were OS in pts with TPS ≥50%, ≥20%, and ≥1%. OS differences were assessed sequentially using the stratified log-rank test. Efficacy boundaries at the prespecified second interim analysis were one-sided P = .0122, .01198, and .01238, respectively. Results: 1274 pts were randomized: 637 to each arm. 599 pts (47.0%) had TPS ≥50%, 818 (64.2%) had TPS ≥20%. After 12.8-mo median follow-up, 13.7% were still on pembro and 4.9% were receiving peme maintenance. Pembro significantly improved OS in pts with TPS ≥50% (HR 0.69), TPS ≥20% (HR 0.77), and TPS ≥1% (HR 0.81) (Table). Grade 3-5 drug-related AEs were less frequent with pembro (17.8% vs 41.0%). The external DMC recommended continuing the trial to evaluate PFS (secondary end-point). Conclusion: KEYNOTE-042 is the first study with a primary end-point of OS to demonstrate superiority of pembro over platinum-based chemo in pts with previously untreated advanced/metastatic NSCLC without sensitizing EGFR or ALK alterations and a PD-L1 TPS ≥1%. These data confirm and potentially extend the role of pembro monotherapy as a standard first-line treatment for PD-L1-expressing advanced/metastatic NSCLC. Clinical trial information: NCT02220894. [Table: see text]
IMpower131: Primary PFS and safety analysis of a randomized phase III study of atezolizumab + carboplatin + paclitaxel or nab-paclitaxel vs carboplatin + nab-paclitaxel as 1L therapy in advanced squamous NSCLC.
Authors: Jotte Robert M. , Cappuzzo Federico , Vynnychenko Ihor , Stroyakovskiy Daniil , Rodriguez Abreu Delvys , Hussein Maen A. , Soo Ross A. , Conter Henry Jacob , Kozuki Toshiyuki , Silva Carlos , Graupner Vilma , Sun Shawn , Lin Ray S , Kelsch Claudia , Kowanetz Marcin , Hoang Tien , Sandler Alan , Socinski Mark A. 
Published: June 2018

LBA9000 Background: Atezolizumab (atezo; anti–PD-L1) demonstrated OS benefit vs docetaxel in 2L+ NSCLC regardless of PD-L1 status or tumor histology. Because cytotoxic agents can exhibit positive immunomodulatory effects, combining atezo with chemotherapy may further improve outcomes. IMpower131 (NCT02367794) was designed to evaluate atezo + carboplatin (carbo) + paclitaxel (pac) or nab-paclitaxel (nab-pac) in 1L stage IV squamous NSCLC. Methods: Patients (pts) were randomized 1:1:1 to Arm A (atezo 1200 mg q3w + carbo AUC 6 q3w + pac 200 mg/m2 q3w), Arm B (atezo + carbo + nab-pac 100 mg/m2 weekly) or Arm C (carbo + nab-pac). Pts received chemotherapy for 4 or 6 cycles and atezo until loss of clinical benefit. We present the primary analysis of investigator (INV)-assessed PFS per RECIST v1.1 in the ITT population for Arm B vs Arm C. Data cutoff: 22 January 2018. Results: 338 pts (Arm A), 343 pts (Arm B) and 340 pts (Arm C) were enrolled. Minimum follow-up was 9.8 mo. INV-assessed median PFS was 6.3 mo in Arm B vs 5.6 mo in Arm C (HR, 0.715; 95% CI: 0.603, 0.848; P = 0.0001). PFS benefit was enriched in all PD-L1–positive IHC subgroups and was most pronounced in TC3 or IC3. AEs related to any treatment (TRAEs) were 91.3% (Arm A), 94.6% (Arm B) and 90.7% (Arm C); Grade 3-4 TRAEs were 42.8% (Arm A), 68.0% (Arm B) and 56.9% (Arm C); serious TRAEs were 22.3% (Arm A), 20.4% (Arm B) and 10.5% (Arm C). Preliminary OS data will be presented. Conclusions: IMpower131 met its co-primary endpoint of INV-assessed PFS in the ITT population in Arm B vs Arm C. The safety profile of atezo + carbo + nab-pac or pac was consistent with the known risks of the individual treatment components; no new safety signals were identified. Clinical trial information: NCT02367794. [Table: see text]