Advances in understanding ischemic acute kidney injury

Acute kidney injury (AKI) is independently associated with increased morbidity and mortality. Ischemia is the leading cause of AKI, and short of supportive measures, no currently available therapy can effectively treat or prevent ischemic AKI. This paper discusses recent developments in the understanding of ischemic AKI pathophysiology, the emerging relationship between ischemic AKI and development of progressive chronic kidney disease, and promising novel therapies currently under investigation. On the basis of recent breakthroughs in understanding the pathophysiology of ischemic AKI, therapies that can treat or even prevent ischemic AKI may become a reality in the near future

Association between two distinct executive tasks in schizophrenia: a functional transcranial Doppler sonography study

BACKGROUND: Schizophrenia is a severe mental disorder involving impairments in executive functioning, which are important cognitive processes that can be assessed by planning tasks such as the Stockings of Cambridge (SOC), and tasks of rule learning/abstraction such as the Wisconsin Card Sorting Test (WCST). We undertook this study to investigate the association between performance during separate phases of SOC and WCST, including mean cerebral blood flow velocity (MFV) measurements in chronic schizophrenia. METHODS: Functional transcranial Doppler sonography (fTCD) was used to assess bilateral MFV changes in the middle (MCA) and anterior (ACA) cerebral arteries. Twenty-two patients with chronic schizophrenia and 20 healthy subjects with similar sociodemographic characteristics performed SOC and WCST during fTCD measurements of the MCA and the ACA. The SOC was varied in terms of easy and difficult problems, and also in terms of separate phases, namely mental planning and movement execution. The WCST performance was assessed separately for maintaining set and set shifting. This allowed us to examine the impact of problem difficulty and the impact of separate phases of a planning task on distinct intervals of WCST. Simultaneous registration of MFV was carried out to investigate the linkage of brain perfusion during the tasks. RESULTS: In patients, slowing of movement execution during easy problems (SOC) was associated with slowing during maintaining set (WCST) (P < 0.01). In healthy subjects, faster planning and movement execution during predominantly difficult problems were associated with increased performance of WCST during set shifting (P < 0.01). In the MCA, patients showed a significant and positive correlation of MFV between movement execution and WCST (P < 0.01). CONCLUSION: The results of this study demonstrate performance and brain perfusion abnormalities in the association pattern of two different tasks of executive functioning in schizophrenia, and they support the notion that executive functions have a pathological functional correlate predominantly in the lateral hemispheres of the brain. This study also underpins the scientific potential of fTCD in assessing brain perfusion in patients with schizophrenia

Factors that influence healing of chronic venous leg ulcers: a retrospective cohort

BACKGROUND: Venous ulcers have a significant impact on patient quality of life, and constitute a worldwide public health problem. Treatment is complex, with high failure rates.OBJECTIVES: To identify clinical and therapeutic factors that influence healing of venous ulcers.METHODS: Retrospective cohort study of patients with venous ulcers. Ulcer area was measured at the first visit (T0) and after 6 months (T6) and 1 year (T12). A reduction in ulcer area of 50% or more at T6 and T12 was the outcome of interest, weighted by clinical, demographic and treatment aspects.RESULTS: Ninety-four patients were included (137 ulcers). A reduction in ulcer area of 50% or more was seen in 40.1% of patients (95% CI 31.9 to 48.4%) at T6 and 49.6% (95% CI 41.2 to 58.1%) at T12. Complete healing occurred in 16.8% (95% CI 10.5 to 23.1%) at T6 and 27% (95% CI 19.5 to 39.5%) at T12. The lowest ulcer area reductions at T6 were associated with longstanding ulcer (RR=0.95; 95% CI 0.91 to 0.98), poor adherence to compression therapy (RR=4.04; 95% CI 1.31 to 12.41), and infection episodes (RR=0.42; 95% CI 0.23 to 0.76). At T12, lower reductions were associated with longstanding ulcer (RR=0.95; 95% CI 0.92 to 0.98), longer topical antibiotic use (RR=0.93; 95% CI 0.87 to 0.99), and systemic antibiotic use (RR=0.63; 95% CI 0.40 to 0.99).CONCLUSIONS: Longstanding ulcer, infection, poor adherence to compression therapy, and longer topical and systemic antibiotic use were independently correlated with worse healing rates.Univ Estadual Paulista, UNESP, Botucatu, SP, BrazilUniv Estadual Paulista, UNESP, Botucatu, SP, Brazi

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Assessment of alterations in regional cerebral blood flow in patients with hypothyroidism due to Hashimoto’s thyroiditis

Aim: The aim of this study was to assess regional cerebral blood flow (rCBF) using detailed semiquantative analysis of Tecnethium-99m hexamethylpropyleneamine (HMPAO) brain single-photon emission computered tomography (SPECT) in patients with hypothyroidism due to autoimmune thyroiditis. Patients, material and methods: Twenty patients (mean age: 42 +/- 9 yr) and 12 control subjects (mean age: 35.4 +/- 8.5 yr) were included in this study. The corticocerebellar rCBF ratios were obtained from 52 cerebral areas on 6 transaxial slices. By using control group rCBF ratios, lower reference values (RLV) (average ratio -2 SD) were calculated and the regions below RLV having an rCBF ratio were considered as abnormal decrease (hypoperfused) areas. Results: Significant reduced rCBF rates were measured for 15 (29%) cortical regions for the patient group. The areas in which significant reduced rCBF were demonstrated in the patient group were as follows: a) in the right hemisphere: superior frontal (slice 1 and 2), inferior frontal (slice 1), anterior temporal (slice 1 and 2), precentral gyrus (slice 1 and 2), postcentral gyrus (slice 1 and 2), and parietal cortex; b) in the left hemisphere: superior frontal (slice 1 and 2), inferior frontal (slice 1), caudate nucleus, and parietal cortex. The hypoperfusion was calculated in 154 (14%, 94 right and 60 left) cortical regions out of 1040 regions in the patient group. Conclusion: These findings indicate that the alteration of rCBF in patients with hypothyroidism due to Hashimoto's thyroiditis before T-4 therapy can be demonstrated with brain SPECT. Additionally, the degree of rCBF abnormalities could be determined with brain SPECT in patients with hypothyroidism due to Hashimoto's thyroiditis with or without neurologic or psychiatric symptoms