Epidemiology of emergency department acute kidney injury

Aim The epidemiology of Acute Kidney Injury (AKI) diagnosed in the Emergency Department (ED) is poorly described. This study describes the incidence, demographics and outcomes of patients diagnosed with AKI in the ED (ED‐AKI). Methods A prospective cohort study was completed in a University Teaching Hospital, (UK) between April and August 2016. In total 20,421 adult patients attended the ED and had a serum creatinine measurement. The incident ED‐AKI patient episodes were compared to a randomly selected cohort of non‐AKI ED patients. Results 572 patients had confirmed eAlert ED‐AKI (548 incident cases), incidence 2.8% (of all ED attendances). ED‐AKI was associated with a 24.4% in‐patient mortality (non‐AKI 3.2%, p<0.001) of which 22.3% of deaths occurred within 24‐hours and 58% within 7‐days. Progression of the admission AKI stage to a higher AKI stage was associated with a 38.8% mortality compared to a 21.4% mortality in those who did not progress (p<0.001). In multivariate analysis ED‐AKI was an independent risk for mortality (HR, 6.293; 95% CI, 1.887 to 20.790, p=0.003). For those discharged from hospital 20.4% of ED‐AKI patients re‐attend for acute assessment within 30‐days post discharge (non‐AKI 7.6%, p<0.001). At 90‐days post discharge 10.0% of ED‐AKI patients died (non‐AKI 1.4%, p<0.001). 12‐months post discharge 17.8% of ED‐AKI patients developed CKD progression or de‐novo CKD (non‐AKI 6.0%). Conclusion ED‐AKI is an independent predictor of death. Mortality is predominantly in the early stages of hospital admission, but for those who survive to discharge have significant long‐term morbidity and mortality

Development of soft computing tools and IoT for improving the performance assessment of analysers in a clinical laboratory

This paper presents a three phase methodology to automate quality control in healthcare clinical laboratory. The first phase consists in the automation of the performance assessment of the equipment in MS Excel. With the smart tools included in Excel, a macro was developed that not only saves the user time and makes the process more efficient, but also gives a clear idea of the quality of the test results. The second phase deals with the quality control management of the generated data through the application of manufacturing techniques; a code in Matlab was created that would allow the user to visualise the current performance of the equipment according to some specified limits in Statistical Process Control (SPC) charts. This enables the user to select the relevant information to visualise by analysing the control levels and dates. In the final phase a prediction algorithm applying data mining and machine learning techniques was developed, based on the historical data, which is used as a small sample of big data that could be potentially generated by the IoT enabled equipment interconnected via the internet enabling them to send and receive data. Using the K-Nearest Neighbour (KNN) classifier a performance accuracy of 94% was achieved which allows the user to predict future behaviour of the equipment

Epidemiology and outcome of community-acquired acute kidney injury

Aims: Very little data exist regarding community-acquired acute renal injury (CA-AKI). We have identified and characterized a patient cohort with CA-AKI, and documented its impact on renal function and patient mortality. Methods: Using the database of the Medical Biochemistry Department of the Cardiff and Vale University Health Board we identified all patients with CA-AKI over a 1 month period in 2009. Follow-up biochemical and clinical data were used to determine short-term (3 months) and long-term (3 years) outcomes. Comparisons were made to a random and an age/sex matched group. Results: Patients with CA-AKI were older than a non-AKI cohort (70.3 vs 57.1 years; P < 0.0001), with a 61% male predominance. 38% had pre-existing chronic kidney disease (CKD) compared with 25% in the age- and sex-matched non-CA-AKI cohort (P = 0.007). 54% of CA-AKI were admitted for inpatient care. Admission was associated with a higher incidence of complete recovery of renal function. Mortality at 3 months was 16.5%, and was related to the severity of AKI. Over the 3 years of follow-up 71% of patients with CA-AKI developed progressive CKD which was more likely following incomplete/no recovery of renal function and in the context of pre-existing CKD. Three year mortality was 45%, which was higher than that of the age/sex matched control cohort (15.7%; P < 0.0001), but was not related to the development of progressive CKD. Conclusions: CA-AKI carries significant implications in terms of both development of progressive renal disease and high long-term patient mortality

Late diagnosis of hypophosphatasia in a case with Unverricht-Lundborg disease

A significant increase in the activity of serum alkaline phosphatase is commonly reported in patients on long-term antiepileptic treatment or after any uncomplicated fracture. We report a case of a 35-year-old male patient on five different anticonvulsant medications for treatment of the rare autosomal recessive neurodegenerative disorder, Unverricht-Lundborg disease. He presented with bilateral metatarsal fractures: however, his serum alkaline phosphatase activity remained below the lower limit of reference interval. Biochemical laboratory investigations revealed a longstanding low serum alkaline phosphatase and raised plasma pyridoxal-5′-phosphate concentration. Sequencing of genomic DNA revealed that he is heterozygous for a mutation in the ALPL gene, which is consistent with the diagnosis of hypophosphatasia

Functional characterization of novel ABCB6 mutations and their clinical implications in familial pseudohyperkalemia

Isolated familial pseudohyperkalemia is a dominant red cell trait characterized by cold-induced 'passive leak' of red cell potassium ions into plasma. The causative gene of this condition is ABCB6, which encodes an erythrocyte membrane ABC transporter protein bearing the Langereis blood group antigen system. In this study analyzing three new families, we report the first functional characterization of ABCB6 mutants, including the homozygous mutation V454A, heterozygous mutation R276W, and compound heterozygous mutations R276W and R723Q (in trans). All these mutations are annotated in public databases, suggesting that familial pseudohyperkalemia could be common in the general population. Indeed, we identified variant R276W in one of 327 random blood donors (0.3%). Four weeks' storage of heterozygous R276W blood cells resulted in massive loss of potassium compared to that from healthy control red blood cells. Moreover, measurement of cation flux demonstrated greater loss of potassium or rubidium ions from HEK-293 cells expressing ABCB6 mutants than from cells expressing wild-type ABCB6. The R276W/R723Q mutations elicited greater cellular potassium ion efflux than did the other mutants tested. In conclusion, ABCB6 missense mutations in red blood cells from subjects with familial pseudohyperkalemia show elevated potassium ion efflux. The prevalence of such individuals in the blood donor population is moderate. The fact that storage of blood from these subjects leads to significantly increased levels of potassium in the plasma could have serious clinical implications for neonates and infants receiving large-volume transfusions of whole blood. Genetic tests for familial pseudohyperkalemia could be added to blood donor pre-screening. Further study of ABCB6 function and trafficking could be informative for the study of other pathologies of red blood cell hydration

Clinical and laboratory characteristics of clozapine-treated patients with schizophrenia referred to a national immunodeficiency clinic reveals a B-cell signature resembling common variable immunodeficiency (CVID)

Aims: An association between antibody deficiency and clozapine use in individuals with schizophrenia has recently been reported. We hypothesised that if clozapine-associated hypogammaglobulinaemia was clinically relevant this would manifest in referral patterns. Methods: Retrospective case note review of patients referred and assessed by Immunology Centre for Wales (ICW) between January 2005 and July 2018 with extraction of clinical and immunological features for individuals with diagnosis of schizophrenia-like illness. Results: 1791 adult patients were assessed at ICW during this period; 23 patients had a psychiatric diagnosis of schizophrenia or schizoaffective disorder. Principal indications for referral were findings of low calculated globulin and immunoglobulins. Clozapine was the single most commonly prescribed antipsychotic (17/23), disproportionately increased relative to reported use in the general schizophrenia population (OR 6.48, 95% CI: 1.79 to 23.5). Clozapine therapy was noted in 6/7 (86%) of patients subsequently requiring immunoglobulin replacement therapy (IgRT). Marked reduction of class-switched memory B cells (CSMB) and plasmablasts were observed in clozapine-treated individuals relative to healthy age-matched controls. Clozapine duration is associated with CSMB decline. One patient discontinued clozapine, with gradual recovery of IgG levels without use of IgRT. Conclusions: Our findings are consistent with enrichment of clozapine-treatment within schizophrenic individuals referred for ICW assessment over the last 13 years. These individuals displayed clinical patterns closely resembling the primary immunodeficiency common variable immunodeficiency, however appears reversible on drug cessation. This has diagnostic, monitoring and treatment implications for psychiatry and immunology teams and directs prospective studies to address causality and the wider implications for this patient group

Phospholipase D activity is essential for actin localization and actin-based motility in Dictyostelium

PLD (phospholipase D) activity catalyses the generation of the lipid messenger phosphatidic acid, which has been implicated in a number of cellular processes, particularly the regulation of membrane traffic. In the present study, we report that disruption of PLD signalling causes unexpectedly profound effects on the actin-based motility of Dictyostelium. Cells in which PLD activity is inhibited by butan-1-ol show a complete loss of actin-based structures, accompanied by relocalization of F-actin into small clusters, and eventually the nucleus, without a visible fall in levels of F-actin. Addition of exogenous phosphatidic acid reverses the effects of butan-1-ol, confirming that these effects are caused by inhibition of PLD. Loss of motility correlates with complete inhibition of endocytosis and a reduction in phagocytosis. Inhibition of PLD caused a major decrease in the synthesis of PtdIns(4,5)P(2), which could again be reversed by exogenously applied phosphatidic acid. Thus the essential role of PLD signalling in both motility and endocytosis appears to be mediated directly via regulation of PtdIns(4)P kinase activity. This implies that localized PLD-regulated synthesis of PtdIns(4,5)P(2) is essential for Dictyostelium actin function