Increased Glaucoma Case-finding Through Routine Optical Coherence Tomography in Optometry Practice.

OBJECTIVE: Timely detection of glaucoma is key to preventing or delaying vision loss. This study aimed to assess whether the routine use of optical coherence tomography (OCT) by optometrists for detection of glaucomatous changes in the optic nerve and retina increased glaucoma referrals to ophthalmologists. DESIGN: This study was a retrospective review of routinely-collected electronic medical records of patients from a chain of 331 optometry practices in Australia. PARTICIPANTS: Electronic medical records were reviewed for every patient aged 18-99 years who attended an included practice between January 1 and July 31, 2019. METHODS: Odds of referral for glaucoma assessment were compared between practices performing OCT routinely on all patients (OCT practices, n=175) and without OCT (non-OCT practices, n=20). A subset of referrals were assessed by ophthalmologists to determine the false positive referral rate. MAIN OUTCOME MEASURES: The primary outcome measure of this study was referral to an ophthalmologist for glaucoma assessment. A secondary outcome was the rate of false positive referrals, analysed in a subset of patients referred for glaucoma assessment. RESULTS: Records from 994,461 patients (59% female) were included and 10,475 (1.1%) were referred for glaucoma assessment. Most referrals were associated with normal intraocular pressure (non-OCT practices: n=496, 66%; OCT practices: n=6,603, 68%). Referral for glaucoma was higher in OCT practices (n=9,719, 1.1%) compared to non-OCT practices (n=756, 0.8%, age-, gender- and location-adjusted odds ratio 1.39, 95% confidence interval 1.10-1.76). Of 318 referred patients (3%, all from OCT practices) for whom ophthalmologist feedback was available, 68 (21%) were considered not to have glaucoma. CONCLUSIONS: The routine use of OCT in optometric practice may lead to more timely glaucoma detection and prevention of avoidable vision loss.

Neutrophil-Enriched Biomarkers and Long-Term Prognosis in Acute Coronary Syndrome: a Systematic Review and Meta-analysis.

Activated neutrophils release a range of inflammatory products that represent potential biomarkers, and there is interest in the prognostic value of these in acute coronary syndrome (ACS) patients. We conducted a systematic review to examine neutrophil-enriched biomarkers and the occurrence of major adverse cardiovascular events (MACE) in patients with ACS. We identified twenty-seven studies including 17,831 patients with ACS. The most studied biomarkers were neutrophil gelatinase-associated lipocalin (NGAL) and myeloperoxidase (MPO). Meta-analyses showed that elevated NGAL was associated with higher MACE rates (unadjusted risk ratio (RR) 1.52, 95% CI 1.12-2.06, p = 0.006) as were elevated MPO levels (unadjusted RR 1.61, 95% CI 1.22-2.13, p = 0.01). There was limited data suggesting that increased levels of calprotectin, proteinase-3 and double-stranded DNA were also associated with MACE. These results suggest that higher levels of neutrophil-enriched biomarkers may be predictive of MACE in patients with ACS, although higher-quality studies are needed to confirm these observations.

A comparison of operative autonomy between men and women in orthopaedic surgical training in Aotearoa New Zealand.

AIM: Recent studies have shown that women training in surgical and procedural specialties achieve less operative autonomy during training than men do. The aim of this study was to discern if there is a disparity in surgical autonomy for orthopaedic trainees by gender. METHODS: This was a retrospective study of operative procedures performed by 53 orthopaedic trainees (43 men, 10 women) in Aotearoa New Zealand over 10 years. The main outcome measure was the amount of surgical autonomy afforded to individual trainees as recorded in the training logbook, categorised as assisting a: primary surgeon with consultant scrubbed or present; or, primary surgeon unsupervised and teaching a colleague the procedure. RESULTS: Data was obtained for 41,622 procedures in total. Eighty point seven percent were performed by men and 19.3% by women. On average men performed 229 cases per year and women performed 251 cases per year. There was an overall significant difference in autonomy between men and women (p <0.001), with men performing more procedures unsupervised than women (45% of all cases versus 39% of all cases). This difference remained significant when trainee year group was accounted for. CONCLUSIONS: We conclude that women orthopaedic trainees in Aotearoa New Zealand perform fewer cases with meaningful autonomy than men. This disparity may have implications for the quality of training received by men versus women.

Diagnostic performance of S100B as a rule-out test for intracranial pathology in head-injured patients presenting to the emergency department who meet NICE Head Injury Guideline criteria for CT-head scan.

BACKGROUND: Traumatic brain injury is a common ED presentation. CT-head utilisation is escalating, exacerbating resource pressure in the ED. The biomarker S100B could assist clinicians with CT-head decisions by excluding intracranial pathology. Diagnostic performance of S100B was assessed in patients meeting National Institute of Health and Clinical Excellence Head Injury Guideline (NICE HIG) criteria for CT-head within 6 and 24 hours of injury. METHODS: This multicentre prospective observational study included adult patients presenting to the ED with head injuries between May 2020 and June 2021. Informed consent was obtained from patients meeting NICE HIG CT-head criteria. A venous blood sample was collected and serum was tested for S100B using a Cobas Elecsys-S100 module; >0.1 µg/mL was the threshold used to indicate a positive test. Intracranial pathology reported on CT-head scan by the duty radiologist was used as the reference standard to review diagnostic performance. RESULTS: This study included 265 patients of whom 35 (13.2%) had positive CT-head findings. Within 6 hours of injury, sensitivity of S100B was 93.8% (95% CI 69.8% to 99.8%) and specificity was 30.8% (22.6% to 40.0%). Negative predictive value (NPV) was 97.3% (95% CI 84.2% to 99.6%) and area under the curve (AUC) was 0.73 (95% CI 0.61 to 0.85; p=0.003). Within 24 hours of injury, sensitivity was 82.9% (95% CI 66.4% to 93.44%) and specificity was 43.0% (95% CI 36.6% to 49.7%). NPV was 94.29% (95% CI 88.7% to 97.2%) and AUC was 0.65 (95% CI 0.56 to 0.74; p=0.046). Theoretically, use of S100B as a rule-out test would have reduced CT-head scans by 27.1% (95% CI 18.9% to 36.8%) within 6 hours and 37.4% (95% CI 32.0% to 47.2%) within 24 hours. The risk of missing a significant injury with this approach would have been 0.75% (95% CI 0.0% to 2.2%) within 6 hours and 2.3% (95% CI 0.5% to 4.1%) within 24 hours. CONCLUSION: Within 6 hours of injury, S100B performed well as a diagnostic test to exclude significant intracranial pathology in low-risk patients presenting with head injury. In theory, if used in addition to NICE HIGs, CT-head rates could reduce by one-quarter with a potential miss rate of <1%.

Increased levels of low density neutrophils (LDNs) in myocardial infarction.

BACKGROUND: Recent evidence suggests that neutrophils are highly plastic cells that can display heterogeneous phenotypes. Low-density neutrophils (LDNs) have been described in many inflammatory conditions, and are thought to represent an immature, hyperactivated subtype of neutrophils. Neutrophils are significantly involved in the inflammatory response to myocardial infarction (MI), although we do not know the extent to which LDNs exist, or function, in MI. This study sought to determine the frequency and phenotype of LDNs in MI patients, compared to healthy subjects (HS). METHODS: LDNs and normal-density neutrophils (NDNs) were isolated from the peripheral blood of MI subjects (n = 12) and HSs (n = 12) using density gradient centrifugation. LDNs and NDNs were analysed by flow cytometry to identify neutrophils (CD66b+CD15+CD14-CD3-CD19- cells) and examine neutrophil activation (CD11b, CD66b and CD15) and maturity (CD33 and CD16). RESULTS: We identified LDNs within the peripheral blood mononuclear cell (PBMC) fraction of blood, and this population is significantly enriched in MI patients (1.04 ± 0.75% of PBMCs), compared to HS (0.29 ± 0.24%, p = .003). Across both cohorts, LDNs express significantly higher levels of CD66b and CD15, indicating a heightened state of activation compared to NDNs. In this study, LDNs were described as CD33highCD16low, compared to CD33lowCD16high NDNs, indicating the immaturity of this neutrophil subtype. CONCLUSIONS: An increase in the frequency of hyperactivated, immature LDNs is an immunological feature of MI. We highlight a potential pathological role of LDNs in MI, which underscores the need to expand our current understanding of this subtype in MI and other cardiovascular diseases (CVDs).

Cluster analysis of extracellular matrix biomarkers predicts the development of impaired systolic function within 1 year of acute myocardial infarction.

The clinical utility of combining extracellular matrix (ECM) biomarkers to predict the development of impaired systolic function following acute myocardial infarction (AMI) remains largely undetermined. A combination of ELISA and multiplexing assays were performed to measure matrix metalloproteinase (MMP)-2, MMP-3, MMP-8, MMP-9, periostin, N-terminal type I procollagen (PINP) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in plasma samples from 120 AMI patients. All patients had an echocardiogram within 1 year of AMI, and were divided into impaired (n = 37, LVEF < 50%) and preserved (n = 83, LVEF ≥ 50%) systolic function groups. Exploratory factor analysis was performed on log-transformed biomarkers using principle axis analysis with Oblimin rotation. Cluster analysis was performed on log-transformed and normalised biomarkers using Ward's method of minimum variance and the squared Euclidean distance metric. Upon univariate analysis, current smoking, prescription of ACE inhibitors at discharge, peak hsTnT > 610 ng/L (median), MMP-8 levels, Factor 1 scores and Cluster One assignment were predictive of impaired systolic function. Upon multivariate analysis, Cluster One assignment (odds ratio [95% CI], 2.74 [1.04-7.23], p = 0.04) remained an independent predictor of systolic dysfunction in combination with clinical variables. These observations support the usefulness of combining ECM biomarkers using cluster analysis for predicting the development of impaired systolic function in AMI patients.

Examining variation and temporal dynamics of extracellular matrix biomarkers following acute myocardial infarction.

Aim: This study investigated an optimal extracellular matrix (ECM) biomarker panel for measurement in acute myocardial infarction (AMI). Materials & methods: Blood samples were collected from 12 healthy volunteers, and from 23 patients during hospital admission (day 1-3) and 6 months following AMI. Protein assays measured: FGFb, MMP-2, -3, -8, -9, osteopontin, periostin, PINP, TGF-ß1, TIMP-1, -4 and VEGF. Results: When compared with healthy levels, seven ECM biomarkers were significantly altered in AMI patients, and six of these biomarkers displayed stable expression during hospital admission. Clinical characteristics and baseline cardiac function were not well correlated with ECM biomarkers. Conclusion: We suggest, MMP-2, MMP-3, MMP-8, MMP-9, periostin, PINP and TIMP-1 may be useful ECM biomarkers for future studies in AMI patients.

Plain language summary The cardiac extracellular matrix (ECM) maintains the structural integrity of the heart, and can be measured in human circulation using ECM biomarkers. Understanding the levels of variation and temporal dynamics that exist in ECM biomarkers following a heart attack is important for establishing an optimal biomarker panel that may be useful in heart research. A single blood sample was collected from 12 healthy volunteers. Multiple bloods samples were collected from 23 heart attack patients during hospital admission (day 1­3) and 6 months post heart attack. About 12 ECM biomarkers were measured from these blood samples. When compared with healthy levels, seven ECM biomarkers were significantly altered in heart attack patients, and six of these biomarkers displayed stable expression during hospital admission. Variability existed within biomarker levels and this was not well described by traditional heart attack risk factors, such as age or heart attack size. Thus, the source of biomarker variability remains unknown in this study. Overall, we suggest these seven ECM biomarkers may be of interest for future studies in the setting of heart attack research.

Nomogram of paediatric male urethral size: A systematic review.

INTRODUCTION: Knowledge of the normal size of the urethral meatus in boys is important for safely performing urethral catheterization and fundamental to the diagnosis and treatment of paediatric urological conditions. However, clinicians often rely subjectively on previous experience and clinical judgement, rather than a robust evidence-base. A systematic review of the literature was undertaken to define the calibre of the male urethral meatus in paediatric age-groups. METHODS: The MEDLINE and EMBASE databases were systematically searched from inception to December 2020 for studies measuring meatal calibre in boys up to 16 years of age. Google Scholar searches along with forward and backward citation tracking identified additional studies. Studies of subjects >16 years, females, or patients with urethral diseases were excluded. RESULTS: Nine articles (2084 paediatric subjects) were included in the final review. Mean meatal calibre increases non-linearly with age, with accelerated growth occurring during infancy (mini-puberty) and adolescence (puberty). Meatal calibre can be approximately grouped by age as follows: neonate (6-10Fr); infant (10-12Fr); child (12-14Fr); and adolescent (14-18Fr). There is substantial individual variability for same-aged children. Meatal calibre has been independently related to height, weight, and penile size, but the effects of ethnicity and circumcision remain unclear. CONCLUSIONS: The evidence-base for this fundamental aspect of paediatric urology includes only a few low-quality studies and is largely derived from one early study of circumcised American boys. Further studies are warranted to establish normative urethral size values based on rigorous, contemporary data with known dependent variables also included.

A combined biomarker approach for characterising extracellular matrix profiles in acute myocardial infarction.

Extracellular matrix (ECM) biomarkers are useful for measuring underlying molecular activity associated with cardiac repair following acute myocardial infarction (AMI). The aim of this study was to conduct exploratory factor analysis (EFA) to examine the interrelationships between ECM biomarkers, and cluster analysis to identify if distinct ECM profiles could distinguish patient risk in AMI. Ten ECM biomarkers were measured from plasma in 140 AMI patients: MMP-2, -3, -8, -9, periostin, procollagen I N-Terminal propeptide, osteopontin, TGF-ß1, TIMP-1 and -4. EFA grouped eight ECM biomarkers into a two-factor solution, which comprised three biomarkers in Factor 1 and five biomarkers in Factor 2. Notably, ECM biomarkers were not separated based on biological function. Cluster analysis grouped AMI patients into three distinct clusters. Cluster One (n = 54) had increased levels of MMP-8, MMP-9, and TGF-B1. Cluster Two (n = 43) had elevated levels of MMP-2, MMP-3, osteopontin, periostin and TIMP-1, and increased high-sensitivity troponin T and GRACE scores. Cluster Three (n = 43) had decreased levels of ECM biomarkers. Circulating ECM biomarkers demonstrated collinearity and entwined biological functions based on EFA analysis. Using cluster analysis, patients with similar clinical presentations could be separated into distinct ECM profiles that were associated with differential patient risk. Clinical significance remains to be determined.

Linking Neutrophil Extracellular Traps and Platelet Activation: A Composite Biomarker Score for Predicting Outcomes after Acute Myocardial Infarction.

BACKGROUND: Activation of both platelets and neutrophils can contribute to the risk of major adverse cardiovascular events (MACE) following acute myocardial infarction (AMI). Neutrophil extracellular traps (NETs) are an important product of the platelet-neutrophil axis and exaggerate vascular damage in cardiovascular disease. Additionally, activated platelets can drive NETosis and are directly linked to thromboembolic risk. Investigating the combined effect of biomarkers for NETosis and platelet activation represents a novel approach to risk prediction post-AMI. Here, we examined the utility of a composite biomarker score, inclusive of both pathways, for predicting MACE post-AMI. METHODS AND RESULTS: In a case-control design, 100 case patients who experienced MACE within 1 year of index admission were matched in a 1:2 ratio with control patients. Serum levels of myeloperoxidase-DNA, neutrophil elastase-DNA, and citrullinated histone H3 were assayed by enzyme-linked immunosorbent assay (ELISA) as markers of NET burden. To measure platelet activation, soluble P-selectin was assayed by ELISA in parallel. Platelet and neutrophil counts were also recorded. Composite biomarker scores, inclusive of biomarkers for NETosis and platelet activation, were assessed using multivariate regression modeling. These composite biomarker scores were independent predictors of 1-year MACE. The strongest association with MACE was observed using a composite of platelet count, soluble P-selectin, and all NET markers (odds ratio: 1.94; 1.16-3.25). CONCLUSION: Here, we demonstrate the importance of combining biomarkers of NETosis and platelet activation for risk prediction in patients with AMI. Combining biomarkers from closely linked, but distinct, biological pathways was more effective than utilizing either type of biomarker alone.

Reducing length of stay for patients presenting to general surgery with acute non-surgical abdominal pain.

BACKGROUND: Acute abdominal pain is a common surgical presentation. We previously found that over the last decade, more patients were admitted to hospital with non-surgical diagnoses (e.g. gastroenteritis, constipation and non-specific abdominal pain) and length of stay and use of imaging (mainly computed tomography scan) for these patients increased. This study aimed to reduce length of stay and use of imaging for patients admitted with non-surgical abdominal pain. METHODS: A prospective study was undertaken in a tertiary centre evaluating length of stay and use of additional imaging in patients with a non-surgical diagnosis after a quality improvement intervention was implemented. RESULTS: A total of 454 patients were included; 204 (44.9%) presented with non-surgical abdominal pain. During the study period, a significant reduction in computed tomography scan requests was observed (38.5-25.0%, P = 0.037) and an increasing proportion of these patients were discharged within 12 h (33.3-57.1%, P = 0.018). The number of re-presentations remained unchanged (P = 0.358). CONCLUSIONS: The study intervention increased the proportion of patients with non-surgical diagnoses that were successfully discharged within 12 h and reduced the use of additional imaging in this group. This may lead to improved use of health care resources for patients with more urgent diagnoses.

Cardiovascular Risk Factor Modification in Asymptomatic Adults and Implications for Pilots.

This study aims to examine the available evidence that supports a more aggressive approach to managing asymptomatic people with low to intermediate cardiovascular risks; to evaluate the appropriate threshold for initiating pharmacologic interventions to treat hyperglycaemia, hyperlipidaemia, and hypertension; and to describe the implications for airline pilots. A systematic search was performed employing an OvidSP interface, including all EBM Reviews, EMBASE, and Ovid MEDLINE databases. Data, including sixteen randomised controlled trials, on the appropriate threshold for initiating pharmacologic interventions were extracted. Studies on the treatment of hyperlipidaemia indicated that the threshold for initiation of intervention in intermediate-risk people is a LDL-C level of 3.36 mmol/l (130 mg/dl). There was no lower limit or optimal LDL-C level below which further reduction was no longer beneficial. Studies on the treatment of hyperglycaemia suggested that a threshold of fasting plasma glucose of ≥5.3 mmol/l (95 mg/dl) and 2-hour postprandial glucose level of 7.8 mmol/l (140 mg/dl) is reasonable for initiating pharmacologic intervention. Initiating treatment to people with a blood pressure of ≥130/≤89 mmHg or ≤139/≥85 mmHg significantly reduced the risk of developing stage 1 hypertension. Multifactorial intervention studies showed that, in hypertensive patients (BP ≥160/≥100 mmHg), initiating treatment to those with a total cholesterol of 6.5 mmol/l (251.35 mg/dl) or higher resulted in a significant reduction in the risk of developing fatal and non-fatal cardiovascular events. The available evidence from large quality trials supports a more aggressive approach to managing hyperglycaemia, hyperlipidaemia, and hypertension in asymptomatic pilots with a 5-year CVD risk of 5-10% and 10-15%.

Association between inflammatory cytokines and long-term adverse outcomes in acute coronary syndromes: A systematic review.

BACKGROUND: Inflammatory cytokines are involved in the pathophysiology of acute coronary syndromes (ACS) and have been associated with major adverse cardiovascular events (MACE). We systematically reviewed studies investigating the ability of multiple cytokines to predict MACE in ACS patients with follow-up of at least one year. METHODS: A Medical Subject Heading search criteria was applied on Ovid Medline(R), EMBASE, EMBASE Classic and Cochrane Library to systematically identify relevant studies published between 1945 and 2017 that had an observational study design or were randomised controlled trials. Studies were excluded if only one cytokine was analysed, follow-up period was less than one year, subjects were non-human, or blood samples were taken more than 10 days from symptom onset. RESULTS: Ten observational studies met the inclusion criteria. Six had acceptable internal validity when evaluated for quality. The studies were varied in terms of study methods (time of blood collection, study population, cytokines assessed, MACE definition, follow-up length) and result reporting, so a meta-analysis could not be conducted. Six of the studies found significant associations between individual cytokines and MACE. Four studies measured the combined effects of multiple cytokines to predict MACE, and all had statistically significant results. CONCLUSION: A combination of multiple cytokines had a better association with MACE than individual cytokines. It appears promising for future studies to determine the optimal multi-marker methodology and confirm its predictive value.

White blood cell subtypes as predictors of adverse cardiac events.

BACKGROUND: White blood cell (WBC) subtypes have been associated with major adverse cardiovascular events (MACEs) in acute myocardial infarction (AMI). More recently, combining neutrophil and lymphocyte counts or lymphocyte and monocyte counts into a ratio has found to be promising for predicting MACE. This study aimed to confirm the association between MACE and the following WBC subtypes: neutrophils, lymphocytes, monocytes, neutrophil-lymphocyte ratio (NLR) and lymphocyte-monocyte ratio (LMR). METHODS: In a cohort of 860 AMI patients, we collected levels of WBC subtypes from the earliest blood tests recorded prior to angiography. Data on baseline demographics and one-year outcomes were also collected. RESULTS: At one year, 130 patients (15.1%) developed MACE. NLR and LMR were significantly associated with MACE on univariate analysis (P = 0.006 and 0.005, respectively). However, when combined into a multivariate model with age, hypertension, prior myocardial infarction and Type 2 diabetes, neither NLR nor LMR had significant associations (odds ratio = 1.058 and 0.966, P = 0.069 and 0.612, respectively). CONCLUSION: As NLR and LMR were correlated with MACE only on univariate analysis, we do not believe that they are predictive enough to be used alone in a clinical setting. Further studies are required to assess the prognostic ability of these ratios in combination with other inflammatory markers.

An IL-6-IL-8 score derived from principal component analysis is predictive of adverse outcome in acute myocardial infarction.

INTRODUCTION: Many studies have shown that elevated biomarkers of inflammation following acute myocardial infarction (AMI) are associated with major adverse cardiovascular events (MACE). However, the optimal way of measuring the complex inflammatory response following AMI has not been determined. In this study we explore the use of principal component analysis (PCA) utilising multiple inflammatory cytokines to generate a combined cytokine score that may be predictive of MACE post-AMI. METHODS: Thirteen inflammatory cytokines were measured in plasma of 317 AMI patients, drawn 48-72 h following symptom onset. Patients were followed-up for one year to determine the incidence of MACE. PCA was used to generate a combined score using six cytokines that were detectable in the majority of patients (IL-1ß, -6, -8, and -10; MCP-1; and RANTES), and using a subset of cytokines that were associated with MACE on univariate analysis. Multivariate models using baseline characteristics, elevated individual cytokines and PCA-derived scores determined independent predictors of MACE. RESULTS: IL-6 and IL-8 were significantly associated with MACE on univariate analysis and were combined using PCA into an IL-6-IL-8 score. The combined cytokine score and IL-6-IL-8 PCA-derived score were both significantly associated with MACE on univariate analysis. In multivariate models IL-6-IL-8 scores (OR = 2.77, p = 0.007) and IL-6 levels (OR = 2.18, p = 0.035) were found to be independent predictors of MACE. CONCLUSION: An IL-6-IL-8 score derived from PCA was found to independently predict MACE at one year and was a stronger predictor than any individual cytokine, which suggests this may be an appropriate strategy to quantify inflammation post-AMI. Further investigation is required to determine the optimal set of cytokines to measure in this context.

Immunoglobulin G levels predicts risk of recurrent adverse cardiovascular events in myocardial infarction patients.

Background: Patients with myocardial infarction (MI) are at an increased risk of experiencing recurrent major adverse cardiovascular events (MACE) but predicting MACE has remained challenging. Immunoglobulins are implicated in cardiovascular disease, although the predictive value of total immunoglobulin G (IgG) has not yet been evaluated in a secondary prevention setting. This study examined whether total IgG is predictive of MACE in an MI population, and how total IgG compared to the predictive value of C-reactive protein (CRP), an acute inflammatory marker. Methods: We conducted a case-control study with 40 MI subjects (cases) who experienced MACE within 1 year of their index admission. Cases were matched for age, sex, diabetes and presentation with 77 controls who did not have MACE. Pre-discharge plasma samples were analysed for total IgG and CRP. Results: We observed higher levels of total plasma IgG in MI subjects with MACE (24.9 (16.2-43.7) mg/mL) compared to controls (18.4 (9.1-37.3) mg/mL; p < 0.05). Higher levels of IgG were associated with increased risk of MACE in our MI population. MI subjects within quartiles 3 and 4 of total IgG had 6 times and 4 times, respectively, the rate of MACE compared to subjects in quartile 1. There was no difference in CRP levels between cases and controls (1.1 (0.5-3.0) vs. 1.9 (0.6-6.1) mg/mL, p = 0.10), and no relationship was observed between CRP and MACE. Conclusion: Pre-discharge IgG level was a better marker for predicting MACE post-MI than CRP, which had no predictive value in this study.

Platelets modulate multiple markers of neutrophil function in response to in vitro Toll-like receptor stimulation.

INTRODUCTION: In addition to their role in facilitating leukocyte-mediated inflammation, platelets can dampen leukocyte pro-inflammatory responses in some contexts. Consequently, platelets are increasingly appreciated as regulators of inflammation. Together, platelets and neutrophils play a role in inflammation through Toll-like receptor (TLR) expression, although we do not fully understand how platelets shape neutrophil responses to TLR stimulation. Here, we aimed to determine the extent to which platelets can modulate neutrophil function in response to in vitro stimulation with TLR4, TLR2/1, and TLR2/6 agonists. METHODS: Neutrophils from 10 healthy individuals were cultured alone or with autologous platelets. Neutrophils ± platelets were left unstimulated or were stimulated with 1 or 100 ng/mL lipopolysaccharide (LPS; a TLR4 agonist), Pam3CSK4 (a TLR2/1 agonist) and fibroblast-stimulating lipopeptide (FSL)-1 (a TLR2/6 agonist). Neutrophil activation and phagocytic activity were assessed by flow cytometry, and elastase and interleukin-8 secretion were assessed by ELISA. RESULTS: The addition of platelets attenuated neutrophil CD66b and CD11b expression in response to various doses of Pam3CSK4 and FSL-1. Furthermore, platelet co-culture was associated with higher CD62L expression (indicating reduced CD62L shedding) in response to these TLR agonists. Platelets also reduced elastase secretion in unstimulated cultures and in response to low-dose TLR stimulation. Conversely, platelet co-culture increased neutrophil phagocytosis in unstimulated cultures and in response to low-dose Pam3CSK4 and FSL-1. Platelets also increased IL-8 secretion in response to low-dose LPS. CONCLUSION: Platelets are complex immunomodulators that can attenuate some, and simultaneously augment other, neutrophil functions. This modulation can occur both in the absence and presence of TLR stimulation.

Can Surgical Registrars Accurately Identify the Urgent from the Non-Urgent Patient Presenting with Acute Abdominal Pain?

BACKGROUND: Acute abdominal pain is a common surgical presentation with a wide range of causes. Differentiating urgent patients from non-urgent patients is important to optimise patient outcomes and the use of hospital resources. The aim of this study was to determine how accurately urgent and non-urgent patients presenting with abdominal pain can be identified. METHODS: A prospective study of consecutive patients admitted with abdominal pain was undertaken. Urgent patients were classified as requiring treatment (theatre, intensive care unit, endoscopy, or radiologic drainage) within 24 h. Differentiation between urgent and non-urgent was made on the basis of the initial assessment prior to the use of advanced imaging. Outcomes were compared to a final classification based on final diagnosis as adjudicated by an expert panel. RESULTS: Of the 301 patients included, 93 (30.9%) were deemed urgent based on initial assessment, compared to 83 (27.6%) on final diagnosis. Overall sensitivity for recognising urgent patients was 74.7% and specificity 89.9%, and overall accuracy was higher for senior registrars compared to junior registrars (p = 0.015). Urgent patients more often looked unwell or had peritonism on examination (39.8 vs. 17.4% and 56.6 vs. 14.7%, respectively, p < 0.001 for both). CONCLUSIONS: Registrars can accurately differentiate urgent from non-urgent patients with acute abdominal pain in the majority of cases. Accuracy was higher amongst senior registrars. The "end-of-the-bed-o-gram" and clinical examination are the most important features used for making this differentiation. This demonstrates that there is no substitute for exposure to acute presentations to improve a trainee's diagnostic skill.