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Inherited defects of vitamin B 2 (riboflavin) metabolism may cause different phenotypes with common biochemical markers of multiple acyl-CoA dehydrogenase deficiency (MADD). Most recently, mutations in FLAD1, which encodes flavin adenine dinucleotide (FAD) synthase, has been implicated in MADD with combined respiratory chain deficiency in nine patients. Here, we describe two siblings with FAD synthase deficiency, who were diagnosed post-mortem upon suspicion of this newly-described disease. Hypotonia was evident at two months of age in both infants, followed by feeding difficulties, respiratory distress and death in six months despite partial response to riboflavin. The older sibling had documented lipid storage myopathy and biochemical markers of MADD. Our observations support the previous reports of unexpected riboflavin-responsiveness in frameshift mutations in the second exon of FLAD1 and suggest dysmorphic auricular helix and hypospadias as possible additional clinical features. More reports and studies are needed to better describe and treat FAD synthase deficiency., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Prognostic uncertainty inhibits clinicians from initiating timely end-of-life discussions and advance care planning. This study evaluates the efficacy of the CriSTAL (Criteria for Screening and Triaging to Appropriate aLternative care) checklist in emergency departments., Methods: Prospective cohort study of patients aged ≥65 years with any diagnosis admitted via emergency departments in ten hospitals in Australia, Denmark and Ireland. Electronic and paper clinical records will be used to extract risk factors such as nursing home residency, physiological deterioration warranting a rapid response call, personal history of active chronic disease, history of hospitalisations or intensive care unit admission in the past year, evidence of proteinuria or ECG abnormalities, and evidence of frailty to be concurrently measured with Fried Score and Clinical Frailty Scale. Patients or their informal caregivers will be contacted by telephone around three months after initial assessment to ascertain survival, self-reported health, post-discharge frailty and health service utilisation since discharge. Logistic regression and bootstrapping techniques and AUROC curves will be used to test the predictive accuracy of CriSTAL for death within 90 days of admission and in-hospital death., Discussion: The CriSTAL checklist is an objective and practical tool for use in emergency departments among older patients to determine individual probability of death in the short-term. Its validation in this cohort is expected to reduce clinicians' prognostic uncertainty on the time to patients' death and encourage timely end-of-life conversations to support clinical decisions with older frail patients and their families about their imminent or future care choices., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Abstract: To determine the validity of the Australian clinical prediction tool Criteria for Screening and Triaging to Appropriate aLternative care (CRISTAL) based on objective clinical criteria to accurately identify risk of death within 3 months of admission among older patients., Methods: Prospective study of ≥ 65 year-olds presenting at emergency departments in five Australian (Aus) and four Danish (DK) hospitals. Logistic regression analysis was used to model factors for death prediction; Sensitivity, specificity, area under the ROC curve and calibration with bootstrapping techniques were used to describe predictive accuracy., Results: 2493 patients, with median age 78-80 years (DK-Aus). The deceased had significantly higher mean CriSTAL with Australian mean of 8.1 (95% CI 7.7-8.6 vs. 5.8 95% CI 5.6-5.9) and Danish mean 7.1 (95% CI 6.6-7.5 vs. 5.5 95% CI 5.4-5.6). The model with Fried Frailty score was optimal for the Australian cohort but prediction with the Clinical Frailty Scale (CFS) was also good (AUROC 0.825 and 0.81, respectively). Values for the Danish cohort were AUROC 0.764 with Fried and 0.794 using CFS. The most significant independent predictors of short-term death in both cohorts were advanced malignancy, frailty, male gender and advanced age. CriSTAL's accuracy was only modest for in-hospital death prediction in either setting., Conclusions: The modified CriSTAL tool (with CFS instead of Fried's frailty instrument) has good discriminant power to improve prognostic certainty of short-term mortality for ED physicians in both health systems. This shows promise in enhancing clinician's confidence in initiating earlier end-of-life discussions., Competing Interests: MC and KH developed the risk prediction tool in 2015 and have tested it retrospectively in several hospitals. This might be perceived by readers as non-financial conflict of interest given their knowledge of the subject matter or materials discussed in this manuscript. However, they have no affiliations with or involvement in any organisation or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; or expert testimony or patent-licensing arrangements), that may influence the validity of the study. All other authors certify that they have NO conflict of interest to report. The analyses were led by two co-authors (RMT and FG) who were not involved in the development of the tool, data collection or outcome ascertainment for this validation study.The study was approved in Australia by the hospital management teams and by the South Eastern Sydney Local Health District Ethics Committee [#15/026 HREC/15/POW/55 and data was stored in the UNSW secure server. The need for approval in Denmark was waivered by the Regional Ethics Committee of Southern Denmark, as this project was considered to be a quality improvement initiative without an intervention [42].Verbal information on the study preceded the request for written informed consent which was obtained from each individual if cognitively competent or their surrogate at the time of recruitment. Participants consented to being interviewed, giving access to hospital records during admission, and being contacted for follow-up outcome ascertainment. The original consent remained with the researchers and a copy went to the patient or their family.

This is a case report of a younger woman admitted to hospital with abdominal pain and weight loss. Four weeks after admittance, she was diagnosed with severe bowel ischaemia at laparotomy. Arteriography showed occlusive disease in the mesenteric arteries, which were treated with a stent. The entire intestine was preserved, apart from 10 cm of jejunum due to bowel perforation. The diagnosis of polyarteritis nodosa was confirmed based on biopsy and clinical symptoms.