bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum Tumor Necrosis Factor-alpha and Interleukin-2 Concentrations in Newly Diagnosed ERBB2 (HER2/neu) Positive Breast Cancer Patients
Authors: Saglam Sezer , Suzme Rafi , Gurdol Figen 
Published: January 2018

Aim Cytokines have been associated with symptoms and adverse outcomes in breast cancer. Overexpression of ERBB2 (c-erb-b2; formerly HER2/neu), which is a member of the epidermal growth receptor family, is associated with involvement of lymph nodes, large tumor size, high grade, steroid receptor negativity, aneuploidy, high proliferation rate, and low overall survival in breast cancer. The aim of the study was to examine whether ERBB2 amplification has any effect on circulating levels of tumor necrosis factor-alpha (TNF-α) and interleukin-2 (IL-2) in breast cancer patients. Material and methods Fifty patients with primary breast carcinoma, classified as either ERBB2 (+) or (-) by the fluorescence in situ hybridization (FISH) technique, were included in the study. Cytokines were studied by ELISA according to the procedure described in the commercial kit. Results IL-2 levels were found significantly higher in ERBB2+ patients than in controls (p<0.05). A significant negative correlation existed between ERBB2 positivity and estrogen receptor status (p=0.004). Plasma TNF-α and IL-2 levels were positively correlated in ERBB2+ breast cancer patients (p<0.01). Conclusion The increase in IL-2 concentrations observed in our study suggests an activation of T cells by ERBB2 peptides.
Evaluation of Cell-free DNA in Urine as a Marker for Bladder Cancer Diagnosis
Authors: Zancan Matelda , Galdi Francesca , Di Tonno Fulvio , Mazzariol Chiara , Orlando Claudio , Malentacchi Francesca , Agostini Marco , Maran Michela , Del Bianco Paola , Fabricio Aline S.C. , Murer Bruno , Pianon Carlo , Gion Massimo 
Published: January 2018

The diagnosis and follow-up of bladder cancer are mainly based on cystoscopy, an invasive method which could be negative in case of flat malignancies such as carcinoma in situ. Other noninvasive diagnostic methods have not yet given satisfactory results. There is a need for a reliable yet noninvasive method for the detection of bladder cancer. Our aim was to investigate whether cell-free DNA quantified in urine (ucf-DNA) could be a useful marker for the diagnosis of bladder cancer. A standard urine test was performed in 150 naturally voided morning urine samples that were processed to obtain a quantitative evaluation of ucf-DNA. Leukocyturia and/or bacteriuria were found in 18 subjects, who were excluded from the study. Statistical analysis was performed on 45 bladder cancer patients and 87 healthy subjects. Ucf-DNA was extracted from urine samples by a spin column-based method and quantified using four different methods: GeneQuant Pro (Amersham Biosciences, Pittsburg, PA, USA), Quant-iT™ DNA high-sensitivity assay kit (Invitrogen, Carlsbad, CA, USA), Real-Time PCR (Applied Biosystems, Foster City, CA, USA), and NanoDrop 1000 (NanoDrop Technologies, Houston, TX, USA). Median free DNA quantification did not differ statistically between bladder cancer patients and healthy subjects. A receiver-operating characteristic (ROC) curve was developed to evaluate the diagnostic performance of ucf-DNA quantification for each method. The area under the ROC curve was 0.578 for GeneQuant Pro, 0.573 for the Quant-iT™ DNA high-sensitivity assay kit, 0.507 for Real-Time PCR, and 0.551 for NanoDrop 1000, which indicated that ucf-DNA quantification by these methods is not able to discriminate between the presence and absence of bladder cancer. No association was found between ucf-DNA quantification and tumor size or tumor focality. In conclusion, ucf-DNA isolated by a spin column-based method and quantified by GeneQuant Pro, Quant-iT™ DNA high-sensitivity assay kit, Real-Time PCR or NanoDrop 1000 does not seem to be a reliable marker for the diagnosis of bladder cancer.
Osteopontin-Igm as a Marker for the Diagnosis of Hepatocellular Carcinoma
Authors: Biasiolo Alessandra , Tono Natascia , Beneduce Luca , Zuin Jessica , Fassina Giorgio , Meo Sabrina , Paccagnella Daniela , Mazzucco Mauro , Farinati Fabio , Giacomin Anna , Vanin Veronica , Aldinio Maria Teresa , Miola Emanuela , Donà Silvio , Matteucci Claudia , Sorrentino Roberta , Rasi Guido , Gatta Angelo , Pontisso Patrizia 
Published: January 2018

Introduction Biomarkers for early hepatocellular carcinoma (HCC) detection are still a clinical need. Recent data indicate that cancer-associated antigens lead to the formation of circulating IgM-linked immune complexes as the result of natural IgM production by the innate immune response. The SCCA-IgM immune complex has already been described for primary liver cancer detection. Osteopontin (OPN) is a member of the SIBLING family of proteins recently shown to be related to tumorigenesis, progression and metastasis in various cancer types. Aim To evaluate the serum levels of the OPN-IgM complex in comparison to the SCCA-IgM complex in patients with HCC. Patients A total of 256 patients were analyzed including 151 patients with HCC (M/F 115/36; mean age ± SD: 67 ± 12 years) and 106 patients with cirrhosis (M/F 68/38; mean age ± SD: 62 ± 12 years). HCC, tested before any therapeutic approach, was mainly of viral etiology (58% HCV, 11% HBV), while alcohol abuse (22%) was the main risk factor for the remaining cases. A similar distribution was found in patients with cirrhosis (46% HCV, 15% HBV, 38% alcohol). Methods Serum levels of OPN-IgM were measured using a homemade ELISA assay with a polyclonal anti-human OPN antibody (Biodesign Int, USA). SCCA-IgM was detected in serum using an ELISA assay kit (Hepa-IC, Xeptagen). Results OPN-IgM was positive in 64/151 (42%) patients with HCC and in 45/106 (42%) patients with cirrhosis (specificity 58%), while the reference biomarker SCCA-IgM showed 35% sensitivity (49/139) and 71 % specificity. When patients were stratified on the basis of etiology, the sensitivity values for OPN-IgM and SCCA-IgM were 51% vs 44% in HCV patients, and 36% vs 23% in the other patients, while the specificity was lower for OPN-IgM (55% vs 69% in HCV patients; 62% vs 72% in the other patients). Combination of the two biomarkers resulted in an increase in sensitivity to 63% for viral etiology and to 40% for nonviral etiology. Conclusion Different IgM-linked biomarkers are detectable in primary liver cancer. OPN-IgM and SCCA-IgM showed a similar behavior, while the combination of these biomarkers increased the diagnostic performance for primary liver cancer.
Circulating Survivin-IGM is a Novel Candidate Biomarker of Cirrhosis and Increases with Child Score in Patients Affected by Liver Diseases
Authors: Matteucci Claudia , Sorrentino Roberta , Ettorre Giuseppe M. , Bellis Lia , Antenucci Anna , Beneduce Luca , Santoro Roberto , Vennarecci Giovanni , Zuin Jessica , Biasiolo Alessandra , Pontisso Patrizia , Pierimarchi Pasquale , Puoti Claudio , Rasi Guido 
Published: January 2018

Background Survivin, also known as BIRC5, is the smallest member of the mammalian IAP family and is a well recognized inhibitor of apoptosis with an important role in cell-cycle regulation. It is detected in fetal and neoplastic adult tissue, but not in normal tissues. Survivin acts on cancer promotion not only by the inhibition of apoptosis but also by acceleration of the proliferative activity of cancer cells and several papers have suggested the involvement of this protein in hepatocarcino-genesis. It has been reported that the detection of HCC biomarkers circulating as IgM immune complexes (ICs) improved the diagnosis and prognosis of HCC. The aim of this study was to compare the expression of survivin as an IgM immune complex in serum from healthy controls and of patients with cirrhosis and patients with HCC to identify a novel biomarker for the monitoring of liver diseases. Methods Serum levels of survivin-IgM from 1 97 individuals, including 39 healthy subjects, 94 patients with cirrhosis and 64 with HCC, were measured by ELISA and the relationship with clinical parameters was evaluated. Results Survivin-IgM was almost undetectable in sera from healthy subjects, high in patients with cirrhosis, and moderately lower in patients with HCC. The survivin-IgM assay was positive in 62 of 94 patients with cirrhosis (66%) and in 28 of 64 patients with HCC (43.7%) using a cut-off of 264.89 AU/mL (specificity of 94%). Statistical analysis showed that IC values were significantly different between groups (cirrhosis versus healthy control group, p<0.001; HCC versus cirrhosis group, p<0.001). Circulating survivin-IgM ICs in patients with HCC were lower than in patients with cirrhosis; in fact, the statistical significance in comparison with healthy subjects was lost. On the other hand, the concentration of circulating survivin-IgM ICs was found to increase with progression of Child score. Conclusions The high expression of survivin-IgM in sera from patients with cirrhosis and the values of sensitivity indicate that survivin-IgM could be a novel candidate biomarker for cirrhotic disease. Furthermore, the increase in ICs with the progression of Child score seems to promote the survivin-IgM immune complex as marker of liver failure. Survivin-IgM was found to be lower in sera from HCC patients. Follow-up studies are in progress to monitor patients with cirrhosis and to validate the association of the downregulation of this marker with progression towards hepatocellular carcinoma.
Clinical significance of cerebral microbleeds on MRI: A comprehensive meta-analysis of risk of intracerebral hemorrhage, ischemic stroke, mortality, and dementia in cohort studies (v1)
Authors: Charidimou Andreas , Shams Sara , Romero Jose R , Ding Jie , Veltkamp Roland , Horstmann Solveig , Eiriksdottir Gudny , van Buchem Mark A , Gudnason Vilmundur , Himali Jayandra J , Gurol M Edip , Viswanathan Anand , Imaizumi Toshio , Vernooij Meike W , Seshadri Sudha , Greenberg Steven M , Benavente Oscar R , Launer Lenore J , Shoamanesh Ashkan ,   for The International META-MICROBLEEDS Initiative
Published: January 2018

Background Cerebral microbleeds can confer a high risk of intracerebral hemorrhage, ischemic stroke, death and dementia, but estimated risks remain imprecise and often conflicting. We investigated the association between cerebral microbleeds presence and these outcomes in a large meta-analysis of all published cohorts including: ischemic stroke/TIA, memory clinic, “high risk” elderly populations, and healthy individuals in population-based studies. Methods Cohorts (with > 100 participants) that assessed cerebral microbleeds presence on MRI, with subsequent follow-up (≥3 months) were identified. The association between cerebral microbleeds and each of the outcomes (ischemic stroke, intracerebral hemorrhage, death, and dementia) was quantified using random effects models of (a) unadjusted crude odds ratios and (b) covariate-adjusted hazard rations. Results We identified 31 cohorts ( n = 20,368): 19 ischemic stroke/TIA ( n = 7672), 4 memory clinic ( n = 1957), 3 high risk elderly ( n = 1458) and 5 population-based cohorts ( n = 11,722). Cerebral microbleeds were associated with an increased risk of ischemic stroke (OR: 2.14; 95% CI: 1.58–2.89 and adj-HR: 2.09; 95% CI: 1.71–2.57), but the relative increase in future intracerebral hemorrhage risk was greater (OR: 4.65; 95% CI: 2.68–8.08 and adj-HR: 3.93; 95% CI: 2.71–5.69). Cerebral microbleeds were an independent predictor of all-cause mortality (adj-HR: 1.36; 95% CI: 1.24–1.48). In three population-based studies, cerebral microbleeds were independently associated with incident dementia (adj-HR: 1.35; 95% CI: 1.00–1.82). Results were overall consistent in analyses stratified by different populations, but with different degrees of heterogeneity. Conclusions Our meta-analysis shows that cerebral microbleeds predict an increased risk of stroke, death, and dementia and provides up-to-date effect sizes across different clinical settings. These pooled estimates can inform clinical decisions and trials, further supporting cerebral microbleeds role as biomarkers of underlying subclinical brain pathology in research and clinical settings.
Characteristics of adolescents requiring intensive care in the United Kingdom: A retrospective cohort study
Authors: Wood Dora , Goodwin Sarah , Pappachan John , Davis Peter , Parslow Roger , Harrison David , Ramnarayan Padmanabhan 
Published: January 2018

Objectives To describe the case mix, resource use and outcomes for adolescents admitted to intensive care units in the UK. Methods Analysis of national prospectively collected data for all adolescents aged 12–19 years admitted to UK adult or paediatric intensive care units. Results There were 37,320 admissions of adolescents during the eight–year study period. Excluding elective surgery, respiratory diagnoses were the most common reason for paediatric intensive care unit (PICU) admission, with trauma and intoxication the most common reasons for adult intensive care unit (AICU) admission. Intensive care unit mortality was 6.0% and 5.7% for those admitted to PICUs and AICUs, respectively. Conclusions Mortality is similar among adolescents admitted to AICUs and PICUs; however, these rates have not been corrected for severity of acute illness or underlying burden of chronic illness, which may be different between AICUs and PICUs. Services planned for the majority of AICU and PICU patients may not be optimal for critically ill adolescents treated in UK intensive care units, who may need special consideration.
Effectiveness of paliperidone long-acting injection in clinical practice
Authors: Deslandes Paul Nicholas , Ward Elan Haf , Norris Kathryn , Sewell Robert David 
Published: January 2018

Background: The efficacy of the long-acting injectable formulation of the antipsychotic paliperidone (paliperidone palmitate) has been investigated in randomized controlled trials. Due to the nature of study designs, these may not be representative of usual clinical practice. The aim of this study was to assess the clinical effectiveness of the long-acting injectable antipsychotic paliperidone palmitate using treatment continuation at 1 year as an outcome. Methods: Patients were initiated on paliperidone palmitate prior to December 2014 in a single health board in Wales (UK). Demographic factors that may have influenced outcome, including diagnosis, age at initiation, sex, inpatient or outpatient status on initiation, were analysed to assess whether they influenced patient outcome. For patients completing 1 year of treatment, inpatient stay in the 12 months prior to and following paliperidone palmitate initiation was compared. Results: Data were available for 64 patients; 41 had a diagnosis of schizophrenia and 7 had previously received clozapine. Continuation rates at 6 and 12 months were 69% and 63% respectively. Treatment continuation was not associated with demographic factors. For continuers, mean inpatient stay pre- and post-initiation was 83.2 ± 105.3 and 73.5 ± 103.3 days respectively ( p = 0.61). The most common reason for discontinuation was lack of effect ( n = 9). Conclusions: The proportion of patients remaining on treatment was comparable to that reported in other naturalistic studies. Prescribing for indications outside the product licence was relatively common, but did not appear to influence outcome, although the number of patients in each group was small. Treatment continuation at 6 months appeared to be a predictor of longer-term outcome.
Diagnostic accuracy of functional, imaging and biochemical tests for patients presenting with chest pain to the emergency department: A systematic review and meta-analysis
Authors: Iannaccone Mario , Gili Sebastiano , De Filippo Ovidio , D’Amico Salvatore , Gagliardi Marco , Bertaina Maurizio , Mazzilli Silvia , Rettegno Sara , Bongiovanni Federica , Gatti Paolo , Ugo Fabrizio , Boccuzzi Giacomo G , Colangelo Salvatore , Prato Silvia , Moretti Claudio , D’Amico Maurizio , Noussan Patrizia , Garbo Roberto , Hildick-Smith David , Gaita Fiorenzo , D’Ascenzo Fabrizio 
Published: January 2018

Background: Non-invasive ischaemia tests and biomarkers are widely adopted to rule out acute coronary syndrome in the emergency department. Their diagnostic accuracy has yet to be precisely defined. Methods: Medline, Cochrane Library CENTRAL, EMBASE and Biomed Central were systematically screened (start date 1 September 2016, end date 1 December 2016). Prospective studies (observational or randomised controlled trial) comparing functional/imaging or biochemical tests for patients presenting with chest pain to the emergency department were included. Results: Overall, 77 studies were included, for a total of 49,541 patients (mean age 59.9 years). Fast and six-hour highly sensitive troponin T protocols did not show significant differences in their ability to detect acute coronary syndromes, as they reported a sensitivity and specificity of 0.89 (95% confidence interval 0.79–0.94) and 0.84 (0.74–0.9) vs 0.89 (0.78–0.94) and 0.83 (0.70–0.92), respectively. The addition of copeptin to troponin increased sensitivity and reduced specificity, without improving diagnostic accuracy. The diagnostic value of non-invasive tests for patients without troponin increase was tested. Coronary computed tomography showed the highest level of diagnostic accuracy (sensitivity 0.93 (0.81–0.98) and specificity 0.90 (0.93–0.94)), along with myocardial perfusion scintigraphy (sensitivity 0.85 (0.77–0.91) and specificity 0.92 (0.83–0.96)). Stress echography was inferior to coronary computed tomography but non-inferior to myocardial perfusion scintigraphy, while exercise testing showed the lower level of diagnostic accuracy. Conclusions: Fast and six-hour highly sensitive troponin T protocols provide an overall similar level of diagnostic accuracy to detect acute coronary syndrome. Among the non-invasive ischaemia tests for patients without troponin increase, coronary computed tomography and myocardial perfusion scintigraphy showed the highest sensitivity and specificity.
Absolute lymphocyte and neutrophil counts in neonatal ischemic brain injury
Authors: Povroznik Jessica M , Engler-Chiurazzi Elizabeth B , Nanavati Tania , Pergami Paola 
Published: January 2018

Objectives: This study aimed to identify differences in absolute neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio between neonates with two forms of ischemic brain injury, hypoxic-ischemic encephalopathy, and acute ischemic stroke, compared to controls. We also aimed to determine whether this neutrophil/lymphocyte response pattern is associated with disease severity or is a consequence of the effects of total-body cooling, an approved treatment for moderate-to-severe hypoxic-ischemic encephalopathy. Methods: A retrospective chart review of 101 neonates with hypoxic-ischemic encephalopathy + total-body cooling (n = 26), hypoxic-ischemic encephalopathy (n = 12), acute ischemic stroke (n = 15), and transient tachypnea of the newborn (n = 48) was conducted; transient tachypnea of the newborn neonates were used as the control group. Absolute neutrophil count and absolute lymphocyte count at three time-intervals (0–12, 12–36, and 36–60 h after birth) were collected, and neutrophil-to-lymphocyte ratio was calculated. Results: Hypoxic-ischemic encephalopathy + total-body cooling neonates demonstrated significant time-interval-dependent changes in absolute lymphocyte count and neutrophil-to-lymphocyte ratio levels compared to transient tachypnea of the newborn and acute ischemic stroke patients. Pooled analysis of absolute lymphocyte count for neonates with acute ischemic stroke and hypoxic-ischemic encephalopathy (not hypoxic-ischemic encephalopathy + total-body cooling) revealed that absolute lymphocyte count changes occurring at 0–12 h are likely due to disease progression, rather than total-body cooling treatment. Conclusion: These data suggest that the neutrophil/lymphocyte response is modulated following neonatal ischemic brain injury, representing a possible target for therapeutic intervention. However, initial severity of hypoxic-ischemic encephalopathy among these patients could also account for the observed changes in the immune response to injury. Thus, additional work to clarify the contributions of cooling therapy and disease severity to neutrophil/lymphocyte response following hypoxic-ischemic encephalopathy in neonates is warranted.
Comparative outcomes of radiofrequency ablation for Barrett's oesophagus with different baseline histology
Authors: Tan Wei Keith , Rattan Arti , O’Donovan Maria , Nuckcheddy Tara , Alias Bincy , Sujendran Vijay , di Pietro Massimiliano 
Published: January 2018

BackgroundRadiofrequency ablation (RFA) is currently recommended for dysplastic Barrett's oesophagus (BO); however, there are limited data on treatment response when stratified by baseline histology.ObjectiveThe objective of this article is to evaluate RFA outcomes and durability for BO with different baseline histology.MethodsPatients treated with RFA between 2007 and 2017 at a single institution were retrospectively included. Outcome measures were: (a) complete remission of dysplasia (CRD) and intestinal metaplasia (CRIM) at 18 months, (b) complication rate and (c) durability of CRD and CRIM.ResultsA total of 148 patients underwent RFA, of whom 113 completed the treatment protocol (21 low‐grade dysplasia (LGD), 46 high‐grade dysplasia (HGD) and 46 intramucosal carcinoma (IMC)). CRD and CRIM were achieved in 94.7% and 78.8% of patients, respectively. When stratified by baseline histology, there was no significant difference in CRD between groups (LGD, 95.2%; HGD, 95.7%; and IMC, 93.5%; p = 0.89). Similarly, there was no significant difference in CRIM between groups (LGD, 71.4%; HGD, 76.1% and IMC, 87.0%; p = 0.39). CRD and CRIM durability at 24 months for LGD, HGD and IMC were 100%, 97.7% and 100% (log rank p = 0.31), and 100%, 89.0% and 95.5%, respectively (log rank p = 0.62).ConclusionBaseline histology is not a predictor of RFA response. Once CRD and CRIM are achieved, these effects are durable over time.
Congenital absence of the portal vein in a cat
Authors: Holloway Andrew , Groot Louise , van der Schaaf Klaartje 
Published: January 2018

Case summary A 9-month-old female neutered domestic shorthair cat presented with a history of episodic ptyalism, lethargy and abnormal behaviour. The clinical signs together with elevated pre- and post-prandial bile acid concentrations were consistent with hepatic encephalopathy (HE). In the absence of a portosystemic shunt (PSS) on abdominal ultrasound, medical management of HE was established with a protein-restricted diet and lactulose and the neurological signs resolved. Following an episode of acute vomiting and haemorrhagic diarrhoea at 19 months of age abdominal ultrasonography was repeated. The portal vein could not be demonstrated ultrasonographically; instead, portal vein tributaries were tortuous and communicated with the caudal vena cava (CdVC) at the level of the left kidney. CT angiography (CTA) confirmed the absence of the portal vein. CTA demonstrated the tortuous terminations of the portal tributaries, and several systemic veins, draining into the CdVC via a large-diameter paracaval vessel at the level of the left kidney. Gastrointestinal signs were stabilised and medical management for HE of a protein-restricted diet and lactulose was re-established. Relevance and novel information Congenital absence of the portal vein has not been described previously in the cat and should be considered in cats presenting with signs suggestive of a PSS and HE. The portal vein in the cat can be demonstrated using ultrasound, but complex congenital vascular malformations of the portal or systemic abdominal veins should be characterised using CTA and further distinguished from other vascular anomalies that may present with similar ultrasonographic features.