Pre-eclampsia is a hypertensive disorder of pregnancy characterised by hypertension and sodium retention by the kidneys. To identify changes in sodium uptake proteins in the tubules of the distal nephron, we studied their expression in urinary extracellular vesicles or exosomes (uEVs). Urine was collected from women with pre-eclampsia or during normal pregnancy, and from healthy non-pregnant controls. uEVs were isolated by centrifugation and analyzed by Western blot. Expression, proteolytic cleavage and phosphorylation was determined by densitometric analysis normalized to the exosome marker CD9. Results showed a significant increase in phosphorylation of the activating S130 site in NKCC2, the drug target for frusemide, in women with pre-eclampsia compared with normal pregnant women. Phosphorylation of the activating sites T101/105 in NKCC2 was similar but the activating T60 site in NCC, the drug target for thiazide diuretics, showed significantly less phosphorylation in pre-eclampsia compared with normal pregnancy. Expression of the larger forms of the α subunit of ENaC, the drug target for amiloride, was significantly greater in pre-eclampsia, with more fragmentation of theγ subunit. The differences observed are predicted to increase the activity of NKCC2 and ENaC while reducing that of NCC. This will increase sodium reabsorption, and so contribute to hypertension in pre-eclampsia.

Background There is no universally accepted age cut‐off for defining young strokes. Aims We aimed to determine, based on the profile of young stroke patients in our regional centre, an appropriate age cut‐off for young strokes. Methods A retrospective analysis of all ischaemic stroke patients admitted to our centre from 2015 to 2017. We identified 391 ischaemic stroke patients; 30 patients between the ages of ≤50, 40 between 51–60 inclusive and 321 ≥ 61 years of age. We collected data on demographic profiles, risk factors and stroke classification using the Trial of Org 10 172 in Acute Stroke Treatment criteria. Results We found significant differences between the ≤50 and ≥61 age groups for most of the risk factors and similarities between the 51–60 inclusive and ≥ 61 age groups. At least one of the six risk factors assessed in the study was present in 86.7% of the youngest group, 97.5% of the intermediate age group and 97.2% in the oldest group. In terms of the mechanisms of stroke, the youngest and oldest age groups in our study differed in the prevalence of cryptogenic, cardioembolic and other causes of stroke. The middle and older age groups had similar mechanisms of stroke. Conclusions The prevalence of vascular risk factors and mechanisms of stroke likewise differed significantly across age groups. This study suggests that 50 years is an appropriate age cut‐off for defining young strokes and reinforces the importance of primary prevention in all age groups.

Background Stroke and diabetes mellitus (DM) are significant interrelated healthcare issues but there is a dearth of data on the prevalence of DM among Australia's regional stroke population. Aims We aimed to determine the prevalence of DM in stroke patients at a large regional centre, including subanalyses on stroke subtypes, glycaemic control and renal function in ischaemic stroke (IS). Methods We conducted a retrospective analysis of all patients (n = 323) with IS or transient ischaemic attack (TIA) admitted to Ballarat Base Hospital from January 2015 to December 2016. Demographic data, cardiovascular risk factors, aetiology/territory of IS, pre‐morbid DM status, indicators of glycaemic control and renal impairment were recorded. Results DM was present in 28.5% of IS and TIA patients, including 4% being newly diagnosed. Among diabetic IS patients, 45.3% had poor glycaemic control (HbA1c ≥7.0%) while 16% had moderate to severe renal impairment (estimated glomerular filtration rate of <30). The majority of IS were partial anterior circulation stroke (53.4%) and cardioembolism was the commonest mechanism (43.5%). We found no significant association between DM and a specific stroke location or mechanism. Conclusions Almost one‐third of IS/TIA patients had DM, with a significant proportion showing poor glycaemic control. The DM prevalence in our cohort was comparable with reported rates from other developed countries. Although we found no association between DM and a particular stroke type or mechanism, it is likely a reflection of our cohort size. Our study demonstrated that DM, as a significant risk factor in IS, warrants early detection and better management strategies.

No abstract

Background Currently there are no guidelines on a safe neutrophil count for intravenous antibiotic (IVAB) cessation and hospital discharge in haematology patients recovering after myelosuppressive chemotherapy complicated by febrile neutropenia (FN). Aims We assessed the safety in stable afebrile patients after recent FN of (i) appropriately stopping IVAB and (ii) early hospital discharge respectively within 24 hrs of absolute neutrophil count (ANC) recovery to ≥0.2x10^9/L. Appropriate cessation required a minimum of 3 days of IVAB and no focus of unresolved infection. Safety was defined as the absence of (i) fever recurrence after IVAB cessation and (ii) readmission in the 10-days post discharge for non-line related bacterial sepsis. Barriers to early discharge were also evaluated. Methods A retrospective, single centre audit on adult haematology patients admitted with AML (n=73 courses of induction or consolidation; 27 patients) or for an autograft (n=68 admissions;65 patients) between 2017-2019 and 2016-2017 respectively. Exclusion criteria included patients with secondary AML, reduced intensity AML chemotherapy (low dose cytarabine or azacitidine) and outpatient IVAB use post-discharge. Patients who continued on oral antibiotics as inpatients or on discharge were included in the analysis. Data were analysed with Mann Whitney U test, Chi square test and Fisher's exact test where appropriate. Results Both cohorts had a median age of 59 years. Autograft conditioning consisted mostly of high dose melphalan alone (57%) or with busulfan (7%) and BEAM (19%). All of the AML regimens contained either intermediate or high-dose cytarabine and/or an anthracycline. Most admissions (n=128; 91%) were complicated by FN, 32% (n=41) with positive blood cultures. Nearly half (n=61; 48%) of FN episodes ceased IVAB appropriately with 22/61 (36%) transitioned to oral antibiotics; another 19 (15%) episodes ceased IVAB prior to ANC ≥0.2. None of these 80 episodes had recurrent fever requiring IVAB resumption. IVAB were continued in the remaining 48 (37%) episodes, due to (a) unresolved fever (n=21) (b) recent bacteraemia or unresolved infective focus (n=17) or (c) empirically at physician discretion (n=10), for a median (range) duration of 3 (1-10), 3 (1-15) and 2 (1-5) days respectively. Thirty-seven (29%) of all FN episodes were discharged on oral antibiotics. Discharge within 24h from ANC≥0.2 occurred in 47% overall; more frequently in AML (60%) vs autograft (32%; p=0.001) patients, predominantly due to less unresolved gastrointestinal toxicity (5% vs 59% respectively). Other barriers to early discharge with an incidence of &gt;5% included IVAB use, persistent fever, analgesia for mainly mucositis and transfusion requirement. Unplanned readmission rates were low (6% autograft, 3% AML) with none due to confirmed non-line related bacteraemia; these did not differ according to discharge ANC (≤0.5 or &gt;0.5; p=0.217). Conclusion In afebrile, clinically stable AML and autograft patients without medico-social barriers to early discharge, IVAB can be ceased and hospital discharges safely done within 24h from recovery ANC≥0.2. Disclosures No relevant conflicts of interest to declare.