Stephen T. McSorley

Immune profiling with a Salmonella Typhi antigen microarray identifies new diagnostic biomarkers of human typhoid

Current serological diagnostic assays for typhoid fever are based on detecting antibodies against Salmonella LPS or flagellum, resulting in a high false-positive rate. Here we used a protein microarray containing 2,724 Salmonella enterica serovar Typhi antigens (>63% of proteome) and identified antibodies against 16 IgG antigens and 77 IgM antigens that were differentially reactive among acute typhoid patients and healthy controls. The IgG target antigens produced a sensitivity of 97% and specificity of 80%, whereas the IgM target antigens produced 97% and 91% sensitivity and specificity, respectively. Our analyses indicated certain features such as membrane association, secretion, and protein expression were significant enriching features of the reactive antigens. About 72% of the serodiagnostic antigens were within the top 25% of the ranked antigen list using a Naïve bayes classifier. These data provide an important resource for improved diagnostics, therapeutics and vaccine development against an important human pathogen.

The role of the systemic inflammatory response in predicting outcomes in patients with advanced inoperable cancer: Systematic review and meta-analysis

INTRODUCTION Cancer remains a leading cause of death worldwide. While a curative intent is the aim of any surgical treatment many patients either present with or go onto develop disseminated disease requiring systemic anti-cancer therapy with a palliative intent. Given their limited life expectancy appropriate allocation of treatment is vital. It is recognised that systemic chemoradiotherapy may shorten the quality/quantity of life in patients with advanced cancer. It is against this background that the present systematic review and meta-analysis of the prognostic value of markers of the systemic inflammatory response in patients with advanced cancer was conducted. METHODS An extensive literature review using targeted medical subject headings was carried out in the MEDLINE, EMBASE, and CDSR databases until the end of 2016. Titles were examined for relevance and studies relating to duplicate datasets, that were not published in English and that did not have full text availability were excluded. Full texts of relevant articles were obtained and were then examined to identify any further relevant articles. RESULTS The majority of studies were retrospective. The systemic inflammatory response, as evidenced by a number of markers at clinical thresholds, was reported to have independent prognostic value, across tumour types and geographical locations. In particular, C-reactive protein (CRP, 63 studies), albumin (33 studies) the Glasgow Prognostic Score (GPS, 44 studies) and the Neutrophil Lymphocyte Ratio (NLR, 59 articles) were consistently validated across tumour types and geographical locations. There was considerable variation in the thresholds reported to have prognostic value when CRP and albumin were examined. There was less variation in the thresholds reported for NLR and still less for the GPS. DISCUSSION The systemic inflammatory response, especially as evidenced by the GPS and NLR, has reliable prognostic value in patients with advanced cancer. Further prospective studies of their clinical utility in randomised clinical trials and in treatment allocation are warranted.

Enhanced Recovery After Surgery: Which Components, If Any, Impact on The Systemic Inflammatory Response Following Colorectal Surgery?: A Systematic Review

AbstractEnhanced Recovery or Fast Track Recovery after Surgery protocols (ERAS) have significantly changed perioperative care following colorectal surgery and are promoted as reducing the stress response to surgery.The present systematic review aimed to examine the impact on the magnitude of the systemic inflammatory response (SIR) for each ERAS component following colorectal surgery using objective markers such as C-reactive protein (CRP) and interleukin-6 (IL-6).A literature search was performed of the US National Library of Medicine (MEDLINE), EMBASE, PubMed, and the Cochrane Database of Systematic Reviews using appropriate keywords and subject headings to February 2015.Included studies had to assess the impact of the selected ERAS component on the SIR using either CRP or IL-6.Nineteen studies, including 1898 patients, were included. Fourteen studies (1246 patients) examined the impact of laparoscopic surgery on the postoperative markers of SIR. Ten of these studies (1040 patients) reported that laparoscopic surgery reduced postoperative CRP. One study (53 patients) reported reduced postoperative CRP using opioid-minimising analgesia. One study (142 patients) reported no change in postoperative CRP following preoperative carbohydrate loading. Two studies (108 patients) reported conflicting results with respect to the impact of goal-directed fluid therapy on postoperative IL-6. No studies examined the effect of other ERAS components, including mechanical bowel preparation, antibiotic prophylaxis, thromboprophylaxis, and avoidance of nasogastric tubes and peritoneal drains on markers of the postoperative SIR following colorectal surgery.The present systematic review shows that, with the exception of laparoscopic surgery, objective evidence of the effect of individual components of ERAS protocols in reducing the stress response following colorectal surgery is limited.

The impact of the type and severity of postoperative complications on long-term outcomes following surgery for colorectal cancer: A systematic review and meta-analysis.

BACKGROUND This systematic review investigated the impact of complications by type (infective vs. non-infective) and severity (using the Clavien Dindo scale) on long-term outcome following surgery for colorectal cancer. METHODS A systematic review was performed using appropriate keywords. Meta-analysis using a random effects model was performed. RESULTS 14 studies were included with a total 18,611 patients. Infective complications had a significant impact on disease free (HR 1.41, 95%CI 1.08-1.83, p=0.01) and overall survival (1.37 95%CI 1.22-1.55, p<0.001). Non-infective complications had no significant impact on either disease free (HR 1.21, 95%CI 0.97-1.52, p=0.09) or overall survival (HR 1.35, 95%CI 0.92-1.97, p=0.12). Complication severity had a significant impact on both disease free (HR 1.41, 95%CI 1.18-1.68, p<0.001) and overall survival (HR 1.45, 95%CI 1.25-1.69, p<0.001). DISCUSSION Both type and severity of postoperative complications have an impact on long-term survival following surgery for colorectal cancer.

Unplanned reoperation within 30 days of surgery for colorectal cancer in NHS Lanarkshire

A recent study of unplanned reoperation within 28 days after colorectal surgery in England found a mean rate of 6.5% and suggested that this be used as a performance indicator. We aimed to find the unplanned 30‐day reoperation rate for patients having colorectal cancer surgery in NHS Lanarkshire.

The role of the systemic inflammatory response in predicting outcomes in patients with operable cancer: Systematic review and meta-analysis

Cancer remains a leading causes of death worldwide and an elevated systemic inflammatory response (SIR) is associated with reduced survival in patients with operable cancer. This review aims to examine the evidence for the role of systemic inflammation based prognostic scores in patients with operable cancers. A wide-ranging literature review using targeted medical subject headings for human studies in English was carried out in the MEDLINE, EMBASE, and CDSR databases until the end of 2016. The SIR has independent prognostic value, across tumour types and geographical locations. In particular neutrophil lymphocyte ratio (NLR) (n = 158), platelet lymphocyte ratio (PLR) (n = 68), lymphocyte monocyte ratio (LMR) (n = 21) and Glasgow Prognostic Score/ modified Glasgow Prognostic Score (GPS/mGPS) (n = 60) were consistently validated. On meta-analysis there was a significant relationship between elevated NLR and overall survival (OS) (p < 0.00001)/ cancer specific survival (CSS) (p < 0.00001), between elevated LMR and OS (p < 0.00001)/CSS (p < 0.00001), and elevated PLR and OS (p < 0.00001)/CSS (p = 0.005). There was also a significant relationship between elevated GPS/mGPS and OS (p < 0.00001)/CSS (p < 0.00001). These results consolidate the prognostic value of the NLR, PLR, LMR and GPS/mGPS in patients with resectable cancers. This is particularly true for the NLR/GPS/mGPS which should form part of the routine preoperative and postoperative workup.

The impact of preoperative corticosteroids on the systemic inflammatory response and postoperative complications following surgery for gastrointestinal cancer: A systematic review and meta-analysis

BACKGROUND This meta-analysis examined the impact of preoperative corticosteroids on interleukin 6 (IL-6), C-reactive protein (CRP), and complications following surgery for gastrointestinal cancer. METHODS A systematic review was performed using appropriate keywords. Random-effects meta-analysis was performed. RESULTS 11 RCTs with 474 patients, were included. Corticosteroids were significantly associated with lower IL-6 on postoperative day 1 (mean difference -148pg/mL, 95% CI -205 to -92, p<0.001), 2 (-33pg/mL, 95% CI -58 to -8, p=0.01), and 3 (-31pg/mL, 95% CI -52 to -11, p=0.002), lower CRP on day 3 (-45mg/L, 95% CI -68 to -21, p<0.001), and 7 (-14mg/L, 95% CI -27 to -1, p=0.04), and fewer postoperative infective complications (OR 0.47, 95% CI 0.26-0.83, p=0.01). CONCLUSION Corticosteroids were associated with reduction in the postoperative systemic inflammatory response and complications following surgery for gastrointestinal cancer.

Grand rounds: müllerianosis of the urinary bladder in a postmenopausal woman.

CASE REPORT 61-year-old postmenopausal woman was referred to our urology outpatient clinic by her general Apractitioner with a 3 month history of dysuria and urinary frequency. This was associated with microscopic hematuria detected on dip-stick urinalysis on 3 occasions over the prior year. She denied abdominal pain, gross hematuria, nocturia, or incontinence. She also denied any postmenopausal bleeding or vaginal discharge. She did not describe any change in bowel habit, rectal bleeding, weight loss, or perianal pain. Her medical history was of essential hypertension and macrocytic anemia, for which she was prescribed ramipril and folic acid. Her only surgical history was of 2 caesarean deliveries. She was a smoker with a 10-pack year history and denied excessive alcohol consumption. Physical examination in the clinic revealed no pallor, jaundice, or lymphadenopathy. Abdominal examination revealed a well-healed lower midline scar. The patient described mild discomfort on palpation of the suprapubic region, however, there were no hernia or masses. Both digital rectal and bimanual examinations were unremarkable.

How and why systemic inflammation worsens quality of life in patients with advanced cancer

ABSTRACT Introduction: The presence of an innate host systemic inflammatory response has been reported to be a negative prognostic factor in a wide group of solid tumour types in both the operable and advanced setting, both local and distant. In addition, this host systemic inflammatory response is associated with both clinician reported patient performance status and self-reported measures of quality of life in patients with cancer. Areas covered: A variety of mechanisms are thought to underlie this, including the influence of the host immune response on physical symptoms such as pain and fatigue, its effect on organ systems associated with physical ability and well being such as skeletal muscle, and bone marrow. Furthermore, this innate inflammatory response is thought to have a direct negative impact on mood through its action on the central nervous system. Expert commentary: It is clear that the host systemic inflammatory response represents a target for intervention in terms of both improving quality of life and prognosis in patients with advanced cancer. Based on this paradigm, future research should focus both on pathways which might be targeted by novel agents, but also on whether existing anti-inflammatory drugs might be of benefit.

The relationship between 18F-FDG-PETCT-derived markers of tumour metabolism and systemic inflammation in patients with recurrent disease following surgery for colorectal cancer

18F‐fluorodeoxyglucose positron emission tomography‐computed tomography (18F‐FDG‐PETCT)‐derived markers of tumour metabolism have been reported to have prognostic significance in a variety of tumours. Host inflammation is also recognized to have prognostic significance. The aim of the present study was to investigate the relationship between these markers and host systemic inflammation in patients undergoing elective surgery for colorectal cancer.