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Pathogenic TMPRSS6 variants impairing matriptase-2 function result in inappropriately high hepcidin levels relative to body iron status, leading to iron refractory iron deficiency anemia (IRIDA). As diagnosing IRIDA can be challenging due to its genotypical and phenotypical heterogeneity, we assessed the transferrin saturation (TSAT)/hepcidin ratio to distinguish IRIDA from multi-causal iron deficiency anemia (IDA). We included 20 IRIDA patients from a registry for rare inherited iron disorders and then enrolled 39 controls with IDA due to other causes. Plasma hepcidin-25 levels were measured by standardized isotope dilution mass spectrometry. IDA controls had not received iron therapy in the last 3 months and C-reactive protein levels were <10.0 mg/L. IRIDA patients had significantly lower TSAT/hepcidin ratios compared to IDA controls, median 0.6%/nM (interquartile range, IQR, 0.4–1.1%/nM) and 16.7%/nM (IQR, 12.0–24.0%/nM), respectively. The area under the curve for the TSAT/hepcidin ratio was 1.000 with 100% sensitivity and specificity (95% confidence intervals 84–100% and 91–100%, respectively) at an optimal cut-off point of 5.6%/nM. The TSAT/hepcidin ratio shows excellent performance in discriminating IRIDA from TMPRSS6-unrelated IDA early in the diagnostic work-up of IDA provided that recent iron therapy and moderate-to-severe inflammation are absent. These observations warrant further exploration in a broader IDA population.

Background Studies on the reliability of the MTS and its predictive power for hospitalisation and mortality in the older population have demonstrated mixed results. The objective is to evaluate the performance of the Manchester Triage System (MTS) in older patients (≥65 years) by assessing the predictive ability of the MTS for emergency department resource utilisation, emergency department length of stay (ED-LOS), hospitalisation, and in-hospital mortality rate. The secondary goal was to evaluate the performance of the MTS in older surgical versus medical patients. Methods A retrospective cohort study was conducted of all emergency department visits by patients ≥65 years between 01 and 09-2011 and 31-08-2012. Performance of the MTS was assessed by comparing the association of the MTS with emergency department resource utilisation, ED-LOS, hospital admission, and in-hospital mortality in older patients and the reference group (18–64 years), and by estimating the area under the receiver operating characteristics curves. Results Data on 7108 emergency department visits by older patients and 13,767 emergency department visits by patients aged 18–64 years were included. In both patient groups, a higher emergency department resource utilisation was associated with a higher MTS urgency. The AUC for the MTS and hospitalisation was 0.74 (95%CI 0.73–0.75) in older patients and 0.76 (95%CI 0.76–0.77) in patients aged 18–64 years. Comparison of the predictive ability of the MTS for in-hospital mortality in older patients with patients aged 18–64 years revealed an AUC of 0.71 (95%CI 0.68–0.74) versus 0.79 (95%CI 0.72–0.85). The majority of older patients (54.8%) were evaluated by a medical specialty and 45.2% by a surgical specialty. The predictive ability of the MTS for hospitalisation and in-hospital mortality was higher in older surgical patients than in medical patients (AUC 0.74, 95%CI 0.72–0.76 and 0.74, 95%CI 0.68–0.81 versus 0.69, 95%CI 0.67–0.71 and 0.66, 95%CI 0.62–0.69). Conclusion The performance of the MTS appeared inferior in older patients than younger patients, illustrated by a worse predictive ability of the MTS for in-hospital mortality in older patients. The MTS demonstrated a better performance in older surgical patients than older medical patients regarding hospitalisation and in-hospital mortality.

ObjectiveTo compare the daily practice of two emergency departments (ED) in the Netherlands, where systemic inflammatory response syndrome (SIRS) criteria and quick Sequential Organ Failure Assessment (qSOFA) score are used differently as screening tools for culture-positive sepsis.DesignA prospective cross-sectional multicentre study.SettingTwo EDs at two European clinical teaching hospitals in the Netherlands.Participants760 patients with suspected infection who met SIRS criteria or had a qualifying qSOFA score who were treated at two EDs in the Netherlands from 1 January to 1 March 2018 were included.MethodsSIRS criteria and qSOFA score were calculated for each patient. The first hospital treated the patients who met SIRS criteria following the worldwide Surviving Sepsis Campaign protocol. At the second hospital, only patients who met the qualifying qSOFA score received this treatment. Therefore, patients could be divided into five groups: (1) SIRS+, qSOFA−, not treated according to protocol (reference group); (2) SIRS+, qSOFA−, treated according to protocol; (3) SIRS+, qSOFA+, treated according to protocol; (4) SIRS−, qSOFA+, not treated according to protocol; (5) SIRS−, qSOFA+, treated according to protocol.Primary and secondary outcome measuresTo prove culture-positive sepsis was present, cultures were used as the primary outcome. Secondary outcomes were in-hospital mortality and intensive care unit (ICU) admission.Results98.9% met SIRS criteria and 11.7% met qSOFA score. Positive predictive values of SIRS criteria and qSOFA score were 41.2% (95% CI 37.4% to 45.2%) and 48.1% (95% CI 37.4% to 58.9%), respectively. HRs were 0.79 (95% CI 0.40 to 1.56, p=0.500), 3.42 (95% CI 1.82 to 6.44, p<0.001), 18.94 (95% CI 2.48 to 144.89, p=0.005) and 4.97 (95% CI 1.44 to 17.16, p=0.011) for groups 2–5, respectively.ConclusionqSOFA score performed as well as SIRS criteria for identifying culture-positive sepsis and performed significantly better for predicting in-hospital mortality and ICU admission. This study shows that SIRS criteria are no longer necessary and recommends qSOFA score as the standard for identifying culture-positive sepsis in the ED.Trial registration numberNL8315.