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C-Reactive Protein Is an Important Biomarker for Prognosis Tumor Recurrence and Treatment Response in Adult Solid Tumors: A Systematic Review
A systematic literature review was done to determine the relationship between elevated CRP and prognosis in people with solid tumors. C-reactive protein (CRP) is a serum acute phase reactant and a well-established inflammatory marker. We also examined the role of CRP to predict treatment response and tumor recurrence.
MeSH (Medical Subject Heading) terms were used to search multiple electronic databases (PubMed, EMBASE, Web of Science, SCOPUS, EBM-Cochrane). Two independent reviewers selected research papers. We also included a quality Assessment (QA) score. Reports with QA scores <50% were excluded. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) methodology was utilized for this review (S1 PRISMA Checklist).
271 articles were identified for final review. There were 45% prospective studies and 52% retrospective. 264 had intermediate QA score (≥50% but <80%); Seven were adequate (80% -100%); A high CRP was predictive of prognosis in 90% (245/271) of studies-80% of the 245 studies by multivariate analysis, 20% by univariate analysis. Many (52%) of the articles were about gastrointestinal malignancies (GI) or kidney malignancies. A high CRP was prognostic in 90% (127 of 141) of the reports in those groups of tumors. CRP was also prognostic in most reports in other solid tumors primary sites.
A high CRP was associated with higher mortality in 90% of reports in people with solid tumors primary sites. This was particularly notable in GI malignancies and kidney malignancies. In other solid tumors (lung, pancreas, hepatocellular cancer, and bladder) an elevated CRP also predicted prognosis. In addition there is also evidence to support the use of CRP to help decide treatment response and identify tumor recurrence. Better designed large scale studies should be conducted to examine these issues more comprehensively.
Journal Article
Definition and classification of cancer cachexia: an international consensus
To develop a framework for the definition and classification of cancer cachexia a panel of experts participated in a formal consensus process, including focus groups and two Delphi rounds. Cancer cachexia was defined as a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. Its pathophysiology is characterised by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism. The agreed diagnostic criterion for cachexia was weight loss greater than 5%, or weight loss greater than 2% in individuals already showing depletion according to current bodyweight and height (body-mass index [BMI] <20 kg/m
2) or skeletal muscle mass (sarcopenia). An agreement was made that the cachexia syndrome can develop progressively through various stages—precachexia to cachexia to refractory cachexia. Severity can be classified according to degree of depletion of energy stores and body protein (BMI) in combination with degree of ongoing weight loss. Assessment for classification and clinical management should include the following domains: anorexia or reduced food intake, catabolic drive, muscle mass and strength, functional and psychosocial impairment. Consensus exists on a framework for the definition and classification of cancer cachexia. After validation, this should aid clinical trial design, development of practice guidelines, and, eventually, routine clinical management.
Journal Article
The pathophysiology of cancer-related fatigue: current controversies
Fatigue is one of the most common and debilitating cancer symptoms, and is associated with impaired quality of life. The exact pathophysiology of cancer-related fatigue (CRF) is poorly understood, but in any individual, it is likely multifactorial and involves inter-related cytokine, muscular, neurotransmitter, and neuroendocrine changes. Underlying CRF mechanisms proposed include central and peripheral hypotheses. Central mechanisms include hypotheses about cytokine dysregulation, hypothalamic-pituitary-adrenal-axis disruption, circadian rhythm disruption, serotonin, and vagal afferent nerve function while peripheral mechanisms include hypotheses about adenosine triphosphate and muscle contractile properties. Currently, these hypotheses are largely based on evidence from other conditions in which fatigue is characteristic. The purpose of this article is to provide a narrative review of the literature and present the current controversies in the pathophysiology of CRF, particularly in relation to central and peripheral hypotheses for CRF. An understanding of pathophysiology may facilitate direct and simple therapeutic interventions for those with cancer.
Journal Article
Animal models of the cancer anorexia–cachexia syndrome
Background and aims
Cancer cachexia, a complex wasting syndrome, is common in palliative medicine. Animal models expand our understanding of its mechanisms. A review of cancer cachexia and anorexia animal models will help investigators make an informed choice of the study model.
Results and discussion
Cancer-anorexia cachexia animal models are numerous. No one is ideal. The choice should depend on the research question. To investigate cancer–anorexia cachexia independent of pro-inflammatory cytokine effects, the MAC16 ADK and XK1 are useful. MAC16 ADK helps study the host’s tumor metabolic effects, independent of any anorexia or inflammation. XK1 is both anorectic and cachectic, but data about it is limited. All other models induce a host inflammatory response. The Walker 256 ADK and MCG 101 are best avoided due to excessive tumor growth. Since individual models do not address all aspects of the syndrome, use of a combination seems wise. Suggested combinations: MAC16-ADK (non-inflammatory and non-anorectic) with YAH-130 (inflammatory, anorectic, and cachectic), Lewis lung carcinoma (slow onset anorexia) or prostate adenocarcinoma (inflammatory, anorectic but not cachectic) with YAH-130.
Journal Article
Serum C-reactive protein is an important and powerful prognostic biomarker in most adult solid tumors
Prognostication in cancer is challenging and inaccurate. C-Reactive Protein (CRP), a cheap and sensitive marker of inflammation may help. This study investigated the relationship between CRP and prognosis in a large cohort of solid tumors with mixed cancer diagnoses and stages.
Electronic medical records of 4931 adults with solid tumors who attended the Taussig Cancer Institute from 2006-2012 were reviewed. Demographic and clinical characteristics were recorded. Maximum CRP (mCRP) was identified for each individual. CRP was analysed as a time-dependent, continuous and categorical variable for association with survival.
Two thirds of patients had a high mCRP. This was consistently associated with shorter survival, even after correction for time from diagnosis, and when analysed as a continuous or a categorical variable. When mCRP values above 10 mg/L were subcategorized, a higher mCRP was always worse. Even among those with normal values, statistically and clinically significant shorter survival was noted at mCRP levels >5 mg/L.
In a large representative cohort of consecutive solid tumor patients the risk of death was clinically and statistically significantly greater with a high mCRP. This was independent of other variables and regardless of statistical method from both dates of diagnosis and test. CRP appeared to be underutilized. Our results support the routine use of CRP as a universal cost-effective independent prognostic indicator in most solid tumors.
Journal Article
Proton pump inhibitors and all-cause mortality in colorectal cancer
Proton pump inhibitors (PPIs) are commonly prescribed medications, but their relationship to mortality in colorectal cancer (CRC) remains poorly understood. This study aims to evaluate the association between PPI use and all-cause mortality IN newly diagnosed CRC. This retrospective cohort study utilized electronic medical records from a network comprising over 80 million patients across 57 healthcare organizations in the USA. We identified adult patients with a first-time CRC diagnosis between January 1, 2010, and December 31, 2022, ensuring at least one year of follow-up. Patients were classified as new users or non-users of PPIs at the time of CRC diagnosis. A lag time of 6 months was adopted to minimize protopathic bias. The primary outcome was all-cause mortality. Patients in the study group were matched with patients controls by using 1:1 propensity matching. The analysis included 252,022 patients (126,011 PPI users and 126,011 non-users) matched on propensity scores. PPI users had a higher mortality risk at 1 year (HR = 1.42), 2 years (HR = 1.44), and over the entire follow-up period (HR = 1.40). Sensitivity analyses, which excluded early outcomes, and ancillary analyses, which compared to those on histamine-2 receptor antagonists, confirmed the robustness of these results. Even for former PPI users, the all-cause mortality HR was 1.39. PPI use was associated with an increased risk of all-cause mortality in CRC patients. These findings highlight the need for further research to explore the underlying mechanisms and clinical implications of PPI use in this population. The study indicates that PPIs are associated with increased all-cause mortality in CRC. This highlights the need for careful consideration when prescribing PPIs to this population.
Journal Article
The psychometric properties of cancer multisymptom assessment instruments: a clinical review
Purpose
Various instruments are used to assess both individual and multiple cancer symptoms. We evaluated the psychometric properties of cancer multisymptom assessment instruments.
Methods
An Ovid MEDLINE search was done. All searches were limited to adults and in English. All instruments published from 2005 to 2014 (and with at least one validity test) were included. We excluded those who only reported content validity. Instruments were categorized by the three major types of symptom measurement scales employed as follows: visual analogue (VAS), verbal rating (VRS), and numerical rating (NRS) scales. They were then examined in two areas: (1) psychometric thoroughness (number of tests) and (2) psychometric strength of evidence (validity, reliability, generalizability). We also assigned an empirical global psychometric quality score (which combined the concepts of thoroughness and strength of evidence) to rank the instruments.
Results
We analyzed 57 instruments (17 original, 40 modifications). They varied in types of scales used, symptom dimensions measured, and time frames evaluated. Of the 57, 10 used VAS, 28 VRS, and 19 NRS. The Edmonton Symptom Assessment System (ESAS), ESAS-Spanish, Hospital Anxiety and Depression Scale (HADS), Profile of Mood States (POMS), Symptom Distress Scale (SDS), M.D. Anderson Symptom Inventory (MDASI)-Russian, and MDASI-Taiwanese were the most comprehensively tested for validity and reliability. The ESAS, ESAS-Spanish, ASDS-2, Memorial Symptom Assessment Scale (MSAS)-SF, POMS, SDS, MDASI (and some translations), and MDASI-Heart Failure all showed good validity and reliability.
Conclusions
The MDASI appeared to be the best overall from a psychometric perspective. This was followed by the ESAS, ESAS-Spanish, POMS, SDS, and some MDASI translations. VRS-based instruments were most common. There was a wide range of psychometric rigor in validation. Consequently, meta-analysis was not possible. Most cancer multisymptom assessment instruments need further extensive validation to establish the excellent reliability and validity required for clinical utility and meaningful research.
Journal Article
Weight Loss in Cancer and the 2017 Common Terminology Criteria for Adverse Events—Dangerous and Misleading
Accurate toxicity reporting in cancer clinical trials is necessary to promote regulatory decision making. Up to 85% of those with some cancers (e.g., oesophagus, head and neck, and pancreas) experience significant progressive weight loss (WL) throughout treatment. Therefore, it is necessary that investigators accurately grade and report WL. We have identified two dangerous and misleading approaches in the CTCAE specific to WL: (1) severity grades and associated clinical descriptions and (2) lack of pretreatment weight and longitudinal weight changes. This review highlights the critical importance of a more accurate, comprehensive and patient‐focused WL assessment in oncology clinical trials and the CTCAE. We offer a path forward for identification and management of this life‐threatening phenomenon, whether it is due to cancer or an antitumor treatment. The National Cancer Institute should consider the following five ideas and concrete action items for future CTCAE versions: (1) Weight assessment has important implications for toxicity determination and prognosis in clinical trials and should be consistently integrated into study reports; (2) Adverse event assessment should be patient‐focused and supported by clinically relevant definitions of each grade level; (3) the CTCAE grades and associated clinical descriptions for WL should be revised to better reflect the impact of WL on trial endpoints and patient safety; (4) WL should be assessed as a continuous variable to capture duration, severity, and trajectory; and (5) WL should be urgently incorporated into the PRO‐CTCAE to define the individual impact.
Journal Article
Review: Symptom clusters: myth or reality?
Clinical experience suggests that many symptoms occur together. In this paper, we examine the rationale and evidence base for symptom clusters in different medical fields, particularly the cluster phenomenon in cancer. Cancer symptom clusters are a reality. Various symptoms that cluster clinically have also been verified statistically. Specific clusters such as nausea—vomiting, anxiety—depression, and cough—dyspnea are evident on both clinical observation and in research investigation. Fatigue—pain and fatigue—insomnia—pain have also been demonstrated statistically as clusters. Another proposed cluster ‘depression—fatigue—pain’ seems relevant to clinical practice. Other clusters may serve only as theoretical models that illustrate possible common biological etiologies in cancer; they need to be validated in future research. Analysis of the literature is complicated by considerable inconsistencies across studies. Discrepancies between clinically defined and statistically obtained clusters raise important questions. We must consider the analytical techniques used, and how methodology might influence cluster occurrence and composition. Further research is warranted to establish universally accepted statistical methods and assessment tools for symptom cluster research.
Journal Article