Interpreting iron studies

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An Evaluation of the BluePump in Kenya and The Gambia

This report presents the results of an evaluation of the Fairwater BluePump, an emerging rural water supply technology in sub-Saharan Africa. Claims about the BluePump’s durability and minimal maintenance requirements have provoked significant interest within the rural water sector. This evaluation set out to assess the suitability of the BluePump as a rural water supply technology, taking into account its operational performance, the experiences of water users, the views of local stakeholders, and the broader contextual factors that impinge upon its sustainability

The impact of preoperative dexamethasone on the magnitude of the postoperative systemic inflammatory response and complications following surgery for colorectal cancer

Background: The magnitude of the postoperative systemic inflammatory response (SIR), as evidenced by C-reactive protein (CRP), is associated with both short- and long-term outcomes following surgery for colorectal cancer. The present study examined the impact of preoperative dexamethasone on the postoperative SIR and complications following elective surgery for colorectal cancer. Methods: Patients who underwent elective surgery, with curative intent, for colorectal cancer at a single center between 2008 and 2016 were included (n = 556) in this study. Data on the use of preoperative dexamethasone were obtained from anesthetic records, and its impact on CRP on postoperative days (PODs) 3 and 4, as well as postoperative complications, was assessed using propensity score matching (n = 276). Results: In the propensity score-matched cohort, preoperative dexamethasone was associated with fewer patients exceeding the established CRP threshold of 150 mg/L on POD 3 (odds ratio [OR] 0.42, 95% confidence interval [CI] 0.26–0.70, p < 0.001) and fewer postoperative complications (OR 0.53, 95% CI 0.33–0.86, p = 0.009). Similar results for both POD 3 CRP and complications were observed when using propensity score-adjusted regression (OR 0.40, 95% CI 0.28–0.57 and OR 0.57, 95% CI 0.41–0.80, respectively) and propensity score stratification (OR 0.41, 95% CI 0.25–0.57 and OR 0.53, 95% CI 0.33–0.86, respectively). Conclusions: Preoperative dexamethasone was associated with a lower postoperative SIR and fewer complications following elective surgery for colorectal cancer

Attitudes of surgeons to the use of postoperative markers of the systemic inflammatory response following elective surgery

Background: Cancer is responsible for 7.6 million deaths worldwide and surgery is the primary modality of a curative outcome. Postoperative care is of considerable importance and it is against this backdrop that a questionnaire based study assessing the attitudes of surgeons to monitoring postoperative systemic inflammation was carried out. Method: A Web based survey including 10 questions on the “attitudes of surgeons to the use of postoperative markers of the systemic inflammatory response following elective surgery” was distributed via email. Two cohorts were approached to participate in the survey. Cohort 1 consisted of 1092 surgeons on the “Association of Coloproctology of Great Britain and Ireland (ACPGBI)” membership list. Cohort 2 consisted of 270 surgeons who had published in this field in the past as identified by two recent reviews. A reminder email was sent out 21 days after the initial email in both cases and the survey was closed after 42 days in both cases. Result: In total 29 surgeons (2.7%) from cohort 1 and 40 surgeons (14.8%) from cohort 2 responded to the survey. The majority of responders were from Europe (77%), were colorectal specialists (64%) and were consultants (84%) and worked in teaching hospitals (54%) and used minimally invasive techniques (87%). The majority of responders measured CRP routinely in the post-operative period (85%) and used CRP to guide their decision making (91%) and believed that CRP monitoring should be incorporated into postoperative guidelines (81%). Conclusion: Although there was a limited response the majority of surgeons surveyed measure the systemic inflammatory response following elective surgery and use CRP measurements together with clinical findings to guide postoperative care. The present results provide a baseline against which future surveys can be compared

Enhanced recovery after surgery

Enhanced 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 relationship between systemic inflammation and stoma formation following anterior resection for rectal cancer: a cross-sectional study

Introduction: There is evidence that temporary defunctioning stoma formation in patients undergoing anterior resection reduces the risk of anastomotic leakage. The aim of the present study was to investigate the relationship between stoma formation, the postoperative systemic inflammatory response and complications following anterior resection for rectal cancer. Methods: Data was recorded prospectively for patients who underwent anterior resection for histologically proven rectal cancer, from 2008 to 2015 at a single centre, n = 167. Patients had routine preoperative and postoperative blood sampling including serum C-reactive protein (CRP). Postoperative complications including anastomotic leakage were recorded. Results: Of the 167 patients, the majority were male (61%) and over 65 years old (56%) with node negative disease (60%). 36 patients (22%) underwent preoperative neoadjuvant treatment. 100 patients (60%) had a stoma formed at the time of surgery. Stoma formation was significantly associated with male sex (69% vs. 50%, p = 0.017), neoadjuvant chemoradiotherapy (30% vs 9%, p = 0.001) and open surgery (71% vs. 55%, p = 0.040). Of those 100 patients who had a stoma formed, 80 had it reversed. Permanent stoma was significantly associated with increasing age (p = 0.011), exceeding the established CRP threshold of 150 mg/L on postoperative day 4 (67% vs 37%, p = 0.039), higher incidence of postoperative complications (76% vs 47%, p = 0.035), anastomotic leakage (24% vs 2%, p = 0.003) and higher Clavien Dindo score (p = 0.036). Conclusions: There was no significant association between stoma formation during anterior resection and the postoperative systemic inflammatory response. However, in these patients both the postoperative systemic inflammatory response and complications were associated with permanent stoma

The relationship between cardiopulmonary exercise test variables, the systemic inflammatory response, and complications following surgery for colorectal cancer

Background: Both preoperative cardiopulmonary exercise test (CPET)-derived measures of fitness and postoperative C-reactive protein (CRP) concentrations are associated with complications following surgery for colorectal cancer. The aim of the present pilot study was to examine the relationship between CPET and postoperative CRP concentrations in this patient group. Methods: Patients who had undergone CPET prior to elective surgery for histologically confirmed colorectal cancer in a single centre between September 2008 and April 2017 were included. Preoperative VO2 at the anaerobic threshold (AT) and peak exercise were recorded, along with preoperative modified Glasgow Prognostic Score (mGPS) and CRP on each postoperative day. Results: Thirty-eight patients were included. The majority were male (30, 79%), over 65 years old (30, 79%), with colonic cancer (23, 61%) and node-negative disease (24, 63%). Fourteen patients (37%) had open surgery and 24 (63%) had a laparoscopic resection. A progressive reduction in VO2 at peak exercise was significantly associated with both increasing American Society of Anesthesiology (ASA) grade (median, ml/kg/min: ASA 1 = 22, ASA 2 = 19, ASA 3 = 15, ASA 4 = 12, p = 0.014) and increasing mGPS (median, ml/kg/min: mGPS 0 = 18, mGPS 1 = 16, mGPS 2 = 14, p = 0.039) There was no significant association between either VO2 at the AT or peak exercise and postoperative CRP. Conclusions: The present pilot study reports a possible association between preoperative CPET-derived measures of exercise tolerance, and the preoperative systemic inflammatory response, but not postoperative CRP in patients undergoing surgery for colorectal cancer

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

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

An investigation into the relationship between the postoperative systemic inflammatory response, complications, and oncologic outcomes following surgery for colorectal cancer

Colorectal cancer is the second most common cause of cancer death in the United Kingdom (UK). At present, surgery remains the cornerstone of its management and is the mainstay of curative treatment. However, surgery for colorectal cancer is associated with significant postoperative morbidity and mortality. These postoperative complications, whether classified by their type or severity, are associated with poorer quality of life, increased socioeconomic and direct healthcare costs, and poorer oncologic outcomes. The stress response to surgery is a neurohormonal and immune response to trauma which seeks to stop haemorrhage, prevent infection, and promote healing. However, an inappropriately exaggerated postoperative systemic inflammatory response is now understood to be associated with infective complications following surgery for colorectal cancer. It is thought that this may occur through the suppression of the adaptive immune system by this overwhelming innate response. However, it’s effect on the longer term and oncologic outcomes is less clear. In addition, the factors which influence this postoperative systemic inflammatory response are unclear. Furthermore, it remains to be determined whether attenuation of the postoperative systemic inflammatory response will improve short and long term outcomes following surgery for colorectal cancer. The work presented in this thesis further examines the relationship between the postoperative systemic inflammatory response, postoperative complications, and long term oncologic outcomes following surgery for colorectal cancer. Several perioperative factors which might influence the postoperative systemic inflammatory response are examined. Finally, the question as to whether attenuation of the postoperative systemic inflammatory response might result in improved outcomes following surgery for colorectal cancer is examined. The magnitude of the postoperative systemic inflammatory response, in particular, exceeding C-reactive protein (CRP) concentrations of 150mg/L on postoperative days 3 or 4, has been reported to be associated with the development of infective type postoperative complications. Chapter 3 examined the relationship between the postoperative systemic inflammatory response and complication severity, reporting that exceeding these CRP thresholds was associated with major complications as defined by Clavien Dindo grades 3 to 5. Although postoperative complications are recognised to have a negative prognostic impact, the relationship between the postoperative systemic inflammatory response and long term oncologic outcome is less clear. The results of Chapter 4 suggest that an exaggerated postoperative systemic inflammatory response has a negative prognostic impact independent of complications following surgery for colorectal cancer. There is already some evidence to suggest that patient and operative factors such as the use of laparoscopic surgery, body mass index (BMI), comorbid disease, and the presence of preoperative systemic inflammation influence the postoperative systemic inflammatory response. Chapters 5 to 11 examined some other important patient and perioperative factors which might have an influence on the postoperative systemic inflammatory response. Chapter 5 reported that BMI and visceral obesity measured by preoperative CT scans are associated with the magnitude of the postoperative systemic inflammatory response and complications in female patients only. Chapter 6 reported no significant association between poorer exercise tolerance, a lower anaerobic threshold as measured by cardiopulmonary exercise testing (CPEX), and the magnitude of the postoperative systemic inflammatory response in a small number of patients. Chapter 7 reported no association between the formation of a temporary defunctioning stoma (at the time of anterior resection for rectal cancer), and the magnitude of the postoperative systemic inflammatory response. Chapter 8 reported that operation duration is not directly associated with the postoperative systemic inflammatory response, instead suggesting that the surgical approach is more important. Chapter 9 reported no association between perioperative blood transfusion and the magnitude of the postoperative systemic inflammatory response, but did find a significant association between preoperative inflammation and anaemia. Chapter 10 reported no association between preoperative neoadjuvant chemoradiotherapy (nCRT) and the magnitude of the postoperative systemic inflammatory response in patients undergoing surgery for rectal cancer. Chapter 11 compared the postoperative systemic inflammatory response of patients undergoing surgery for colorectal cancer in the UK and Japan, using propensity scoring to match patients from each country by various demographic, pathological, and perioperative variables. The results suggest a significant difference in the magnitude of the postoperative systemic inflammatory response, possibly dependent on ethnicity, which appears to be confirmed on further examination of the literature. Chapter 12 examined the possibility of a new paradigm of postoperative care following surgery for colorectal cancer. At present the investigation of potential complications following surgery is primarily reactive in nature and based on markers of patient physiology such as heart rate, core body temperature, blood pressure etc. Chapter 12 proposed the use of CRP on day 4 to prompt early investigation of such potential complications by computed tomography (CT) in the presence of an exaggerated postoperative systemic inflammatory response. The results suggest that such a postoperative care protocol could result in the earlier and more accurate diagnosis of postoperative complications. Chapters 13 to 15 examined the use of single dose preoperative corticosteroids for the attenuation of the postoperative systemic inflammatory response and whether it might improve short term complications following surgery for colorectal cancer. Meta-analysis of the existing randomised controlled trials in gastrointestinal cancer surgery in Chapter 13 reported that corticosteroids result in lower postoperative CRP concentrations and fewer postoperative complications, but only in patients undergoing oesophageal and hepatic surgery and not in patients having a colorectal resection. In Chapter 14, a propensity score matched analysis of the GRI cohort of patients given dexamethasone at the induction of anaesthesia, for the prevention of postoperative nausea and vomiting (PONV), reported a significant reduction in postoperative CRP concentrations and complications. Finally, Chapter 15 set out a protocol for a randomised controlled trial of preoperative dexamethasone to assess dose response with relation to the magnitude of the postoperative systemic inflammatory response. In summary, the postoperative systemic inflammatory response may impact on the short and long term outcomes of patients undergoing surgery for colorectal cancer. Attenuation of this postoperative systemic inflammatory response might reduce the rate of postoperative complications, although the impact of such strategies on long term outcomes is as yet unknown. Future research in this area might examine various methods of attenuating the postoperative systemic inflammatory response; including anaesthetic techniques, the use of minimally invasive surgery, and pharmacological techniques such perioperative steroids and other anti-inflammatory drugs, and their impact on short and long term outcomes after surgery for colorectal cancer

Clinicopathological determinants of an elevated systemic inflammatory response following elective potentially curative resection for colorectal cancer

Introduction: The postoperative systemic inflammatory response (SIR) is related to both long- and short-term outcomes following surgery for colorectal cancer. However, it is not clear which clinicopathological factors are associated with the magnitude of the postoperative SIR. The present study was designed to determine the clinicopathological determinants of the postoperative systemic inflammatory response following colorectal cancer resection. Methods: Patients with a histologically proven diagnosis of colorectal cancer who underwent elective, potentially curative resection during a period from 1999 to 2013 were included in the study (n = 752). Clinicopathological data and the postoperative SIR, as evidenced by postoperative Glasgow Prognostic Score (poGPS), were recorded in a prospectively maintained database. Results: The majority of patients were aged 65 years or older, male, were overweight or obese, and had an open resection. After adjustment for year of operation, a high day 3 poGPS was independently associated with American Society of Anesthesiologists (ASA) grade (hazard ratio [HR] 1.96; confidence interval [CI] 1.25–3.09; p = 0.003), body mass index (BMI) (HR 1.60; CI 1.07–2.38; p = 0.001), mGPS (HR 2.03; CI 1.35–3.03; p = 0.001), and tumour site (HR 2.99; CI 1.56–5.71; p < 0.001). After adjustment for year of operation, a high day 4 poGPS was independently associated with ASA grade (HR 1.65; CI 1.06–2.57; p = 0.028), mGPS (HR 1.81; CI 1.22–2.68; p = 0.003), NLR (HR 0.50; CI 0.26–0.95; p = 0.034), and tumour site (HR 2.90; CI 1.49–5.65; p = 0.002). Conclusions: ASA grade, BMI, mGPS, and tumour site were consistently associated with the magnitude of the postoperative systemic inflammatory response, evidenced by a high poGPS on days 3 and 4, in patients undergoing elective potentially curative resection for colorectal cancer