Cancer incidence is increasing in the United Kingdom, as well as on a global basis. Biochemical parameters, such as C-reactive protein and albumin (combined to form the modified Glasgow Prognostic ...Score, mGPS), alkaline phosphatase (Alk phos), gamma-glutamyl transferase (GGT) and serum calcium have been reported to be associated with cancer and non-cancer mortality. Therefore, to definitively examine the interrelationships between the above biochemical parameters, the mGPS and the presence of cancer, the Glasgow Inflammation Outcome Study was undertaken. The aim of this initial study was to examine the effect of cancer on markers of systemic inflammation induced by the liver (mGPS) and on levels of routine biochemical parameters.
Patients (n=223 303) who had a single incidental sample taken for C-reactive protein, albumin, calcium and serum liver function tests where available, between 2000 and 2008 were studied. Those with a pathological diagnosis of cancer (n=22 715) were identified. The mGPS was constructed and liver function tests classified in accordance with the local reference ranges.
Patients with cancer had higher C-reactive protein and lower albumin levels (and thus a higher mGPS), higher adjusted calcium, Alk phos and GGT levels, but lower aspartate transaminase (AST) and alanine transaminase (ALT) levels (all P<0.001). The strongest associations (Spearman's correlation > or =0.3) in both the non-cancer and cancer groups were found between albumin, C-reactive protein and Alk phos, AST and ALT, AST and GGT and ALT and GGT (all P<0.001). On multivariate analysis, the associations with the presence of cancer remained with age, deprivation, C-reactive protein, albumin, adjusted calcium, Alk phos and GGT (all P<0.01). Patients following a diagnosis of cancer had lower albumin levels and thus higher mGPS (all P<0.001). Also, post-diagnosis patients were more likely to have lower adjusted calcium, bilirubin, Alk Phos, AST, ALT and GGT levels (all P<0.05). When the cancer diagnoses were ranked from those with the lowest proportion of mGPS 1 or 2 to those with the highest, the percentage of cases with a mGPS of 1 or 2 ranged from 21% in breast cancer to 46% in prostate cancer and to 68% in pulmonary cancer. Compared with breast cancer the mGPS was significantly higher in those diagnosed with dermatological, bladder, endocrinological, gynaecological, prostate, musculoskeletal, gastroesophageal, haematological, renal, colorectal, head and neck, pancreaticobiliary and pulmonary cancers (all P<0.001).
The results of the present study indicate that the systemic inflammatory response is common in a large patient cohort, increased by the presence of cancer and associated with the perturbation of a number of biochemical parameters previously reported to be associated with mortality. There is a striking parallel between the proportions of cases with a mGPS of 1 or 2 and reported survival rates in these tumours.
A selective combination of C-reactive protein and albumin (termed the modified Glasgow Prognostic Score, mGPS) has been shown to have prognostic value, independent of tumour stage, in lung, ...gastrointestinal and renal cancers. It is also of interest that liver function tests such as bilirubin, alkaline phosphatase and γ-glutamyl transferase, as well as serum calcium, have also been reported to predict cancer survival. The aim of the present study was to examine the relationship between an inflammation-based prognostic score (mGPS), biochemical parameters, tumour site and survival in a large cohort of patients with cancer.
Patients (n=21,669) who had an incidental blood sample taken between 2000 and 2006 for C-reactive protein, albumin and calcium (and liver function tests where available) and a diagnosis of cancer were identified. Of this group 9608 patients who had an ongoing malignant process were studied (sampled within 2 years before diagnosis). Also a subgroup of 5397 sampled at the time of diagnosis (sampled within 2 months prior to diagnosis) were examined. Cancers were grouped by tumour site in accordance with International Classification of Diseases 10 (ICD 10).
On follow up, there were 6005 (63%) deaths of which 5122 (53%) were cancer deaths. The median time from blood sampling to diagnosis was 1.4 months. Increasing age, male gender and increasing deprivation was associated with a reduced 5-year overall and cancer-specific survival (all P<0.001). An elevated mGPS, adjusted calcium, bilirubin, alkaline phosphatase, aspartate transaminase, alanine transaminase and γ-glutamyl transferase were associated with a reduced 5-year overall and cancer-specific survival (independent of age, sex and deprivation in all patients sampled), as well as within the time of diagnosis subgroup (all P<0.001). An increasing mGPS was predictive of a reduced cancer-specific survival in all cancers (all P<0.001).
The results of the present study indicate that the mGPS is a powerful prognostic factor when compared with other biochemical parameters and independent of tumour site in patients with cancer.
The neutrophil lymphocyte ratio (NLR) has prognostic value in patients with a variety of cancers. Many chemotherapeutic trial databases hold information on white cell and neutrophil counts only. The ...aim of the present study was to compare the prognostic value of the NLR with a derived score (dNLR), composed of white cell and neutrophil counts.
Patients (n=27,031) who were sampled incidentally between 2000 and 2007 for neutrophil, lymphocyte and white cell counts, and also had a diagnosis of cancer (Scottish Cancer Registry), were identified. Of this group, 12,118 patients who had been sampled within 2 years of their cancer diagnosis were studied.
On follow-up, there were 7366 deaths, of which 6198 (84%) were cancer deaths. The median time from blood sampling to diagnosis was 2.1 months. The area under the receiver-operating characteristic (ROC) curve for cancer-specific survival was 0.650 for the NLR and 0.640 for the dNLR. The NLR and dNLR were independently associated with survival in all cancers studied (all P<0.001). The optimal thresholds, on the basis of hazard ratios and area under the curve, were 4 : 1 for the NLR and 2 : 1 for the dNLR.
The results of the present study show that the dNLR has similar prognostic value to the NLR. Therefore, the universally available dNLR is to be commended for use in the risk stratification of patients undergoing chemotherapy.
ABSTRACT Results of the application of pattern-recognition techniques to the problem of identifying giant radio sources (GRSs) from the data in the NVSS catalog are presented, and issues affecting ...the process are explored. Decision-tree pattern-recognition software was applied to training-set source pairs developed from known NVSS large-angular-size radio galaxies. The full training set consisted of 51,195 source pairs, 48 of which were known GRSs for which each lobe was primarily represented by a single catalog component. The source pairs had a maximum separation of and a minimum component area of 1.87 square arcmin at the 1.4 mJy level. The importance of comparing the resulting probability distributions of the training and application sets for cases of unknown class ratio is demonstrated. The probability of correctly ranking a randomly selected (GRS, non-GRS) pair from the best of the tested classifiers was determined to be 97.8 1.5%. The best classifiers were applied to the over 870,000 candidate pairs from the entire catalog. Images of higher-ranked sources were visually screened, and a table of over 1600 candidates, including morphological annotation, is presented. These systems include doubles and triples, wide-angle tail and narrow-angle tail, S- or Z-shaped systems, and core-jets and resolved cores. While some resolved-lobe systems are recovered with this technique, generally it is expected that such systems would require a different approach.
The morphology of selected groups of sources in the Faint Images of the Radio Sky at Twenty Centimeters (FIRST) survey and catalog is examined. Sources in the FIRST catalog (2003 April release, ...811,117 entries) were sorted into singles, doubles, triples, and groups of higher-count membership based on a proximity criteria. The 7106 groups with four or more components were examined individually for bent types including, but not limited to, wide-angle tail and narrow-angle tail types. In the process of this examination, ring, double-double, X-shaped, hybrid morphology, giant radio sources, and the herein described W-shaped and tri-axial morphology systems were also identified. For the convenience of the reader separate tables for distinctive types were generated. A few curiosities were found. For the 16,950 three-component groups and 74,788 two-component groups, catalogs with probability estimates for bent classification, as determined by pattern recognition techniques, are presented.
Inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease are chronic, relapsing and remitting disorders of intestinal inflammation with potential systemic manifestations. ...Despite the availability of current biologics, such as anti-tumor necrosis factor (anti-TNF), anti-integrins, anti-interleukins and small molecules such as tofacitinib, the rates of primary and secondary treatment failure remain high in IBD. This highlights the importance of continued development of new therapeutic targets and modifications of existing ones to improve the treatment response rates and to also improve the safety profile and tolerability of these medications. In this review we will discuss novel treatment target agents including selective janus kinase (JAK) inhibitors, anti-interleukin (IL) (IL-12/IL-23), leukocyte trafficking/migrating inhibitors (such as sphingosine-1-phosphate receptor modulator) and other small molecules currently in development.
Markers of the systemic inflammatory response, including C-reactive protein and albumin (combined to form the modified Glasgow Prognostic Score), as well as neutrophil, lymphocyte and platelet counts ...have been shown to be prognostic of survival in patients with cancer. The aim of the present study was to examine the prognostic relationship between these markers of the systemic inflammatory response and all-cause, cancer, cardiovascular and cerebrovascular mortality in a large incidentally sampled cohort.
Patients (n = 160 481) who had an incidental blood sample taken between 2000 and 2008 were studied for the prognostic value of C-reactive protein (>10mg/l, albumin (>35mg/l), neutrophil (>7.5×109/l) lymphocyte and platelet counts. Also, patients (n = 52 091) sampled following the introduction of high sensitivity C-reactive protein (>3mg/l) measurements were studied. A combination of these markers, to make cumulative inflammation-based scores, were investigated.
In all patients (n = 160 481) C-reactive protein (>10mg/l) (HR 2.71, p<0.001), albumin (>35mg/l) (HR 3.68, p<0.001) and neutrophil counts (HR 2.18, p<0.001) were independently predictive of all-cause mortality. These associations were also observed in cancer, cardiovascular and cerebrovascular mortality before and after the introduction of high sensitivity C-reactive protein measurements (>3mg/l) (n = 52 091). A combination of high sensitivity C-reactive protein (>3mg/l), albumin and neutrophil count predicted all-cause (HR 7.37, p<0.001, AUC 0.723), cancer (HR 9.32, p<0.001, AUC 0.731), cardiovascular (HR 4.03, p<0.001, AUC 0.650) and cerebrovascular (HR 3.10, p<0.001, AUC 0.623) mortality.
The results of the present study showed that an inflammation-based prognostic score, combining high sensitivity C-reactive protein, albumin and neutrophil count is prognostic of all-cause mortality.
HHT is an autosomal dominant disease with an estimated prevalence of at least 1/5000 which can frequently be complicated by the presence of clinically significant arteriovenous malformations in the ...brain, lung, gastrointestinal tract and liver. HHT is under-diagnosed and families may be unaware of the available screening and treatment, leading to unnecessary stroke and life-threatening hemorrhage in children and adults.
The goal of this international HHT guidelines process was to develop evidence-informed consensus guidelines regarding the diagnosis of HHT and the prevention of HHT-related complications and treatment of symptomatic disease.
The overall guidelines process was developed using the AGREE framework, using a systematic search strategy and literature retrieval with incorporation of expert evidence in a structured consensus process where published literature was lacking. The Guidelines Working Group included experts (clinical and genetic) from eleven countries, in all aspects of HHT, guidelines methodologists, health care workers, health care administrators, HHT clinic staff, medical trainees, patient advocacy representatives and patients with HHT. The Working Group determined clinically relevant questions during the pre-conference process. The literature search was conducted using the OVID MEDLINE database, from 1966 to October 2006. The Working Group subsequently convened at the Guidelines Conference to partake in a structured consensus process using the evidence tables generated from the systematic searches.
The outcome of the conference was the generation of 33 recommendations for the diagnosis and management of HHT, with at least 80% agreement amongst the expert panel for 30 of the 33 recommendations.
Diminished bioavailability of nitric oxide (NO), the gaseous signaling molecule involved in the regulation of numerous vital biological functions, contributes to the development and progression of ...multiple age- and lifestyle-related diseases. While l-arginine is the precursor for the synthesis of NO by endothelial-nitric oxide synthase (eNOS), oral l-arginine supplementation is largely ineffective at increasing NO synthesis and/or bioavailability for a variety of reasons. l-citrulline, found in high concentrations in watermelon, is a neutral alpha-amino acid formed by enzymes in the mitochondria that also serves as a substrate for recycling l-arginine. Unlike l-arginine, l-citrulline is not quantitatively extracted from the gastrointestinal tract (i.e., enterocytes) or liver and its supplementation is therefore more effective at increasing l-arginine levels and NO synthesis. Supplementation with l-citrulline has shown promise as a blood pressure lowering intervention (both resting and stress-induced) in adults with pre-/hypertension, with pre-clinical (animal) evidence for atherogenic-endothelial protection. Preliminary evidence is also available for l-citrulline-induced benefits to muscle and metabolic health (via vascular and non-vascular pathways) in susceptible/older populations. In this review, we examine the impact of supplementing this important urea cycle intermediate on cardiovascular and metabolic health outcomes and identify future directions for investigating its therapeutic impact on cardiometabolic health.
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