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Background: Preeclampsia is a syndrome of high blood pressure (BP) with end organ damage in late pregnancy that is associated with high circulating soluble VEGF receptor (sFlt1 [soluble Fms-like tyrosine kinase 1]). Women exposed to preeclampsia have a substantially increased risk of hypertension after pregnancy, but the mechanism remains unknown, leaving a missed interventional opportunity. After preeclampsia, women have enhanced sensitivity to hypertensive stress. Since smooth muscle cell mineralocorticoid receptors (SMC-MR) are activated by hypertensive stimuli, we hypothesized that high sFlt1 exposure in pregnancy induces a postpartum state of enhanced SMC-MR responsiveness., Methods: Postpartum BP response to high salt intake was studied in women with prior preeclampsia. MR transcriptional activity was assessed in vitro in sFlt1-treated SMC by reporter assays and PCR. Preeclampsia was modeled by transient sFlt1 expression in pregnant mice. Two months post-partum, mice were exposed to high salt and then to AngII (angiotensin II) and BP and vasoconstriction were measured., Results: Women exposed to preeclampsia had significantly enhanced salt sensitivity of BP verses those with a normotensive pregnancy. sFlt1 overexpression during pregnancy in mice induced elevated BP and glomerular endotheliosis, which resolved post-partum. The sFlt1 exposed post-partum mice had significantly increased BP response to 4% salt diet and to AngII infusion. In vitro, SMC-MR transcriptional activity in response to aldosterone or AngII was significantly increased after transient exposure to sFlt1 as was aldosterone-induced expression of AngII type 1 receptor. Post-partum, SMC-MR-KO mice were protected from the enhanced response to hypertensive stimuli after preeclampsia. Mechanistically, preeclampsia mice exposed to postpartum hypertensive stimuli develop enhanced aortic stiffness, microvascular myogenic tone, AngII constriction, and AngII type 1 receptor expression, all of which were prevented in SMC-MR-KO littermates., Conclusions: These data support that sFlt1-induced vascular injury during preeclampsia produces a persistent state of enhanced sensitivity of SMC-MR to activation. This contributes to postpartum hypertension in response to common stresses and supports testing of MR antagonism to mitigate the increased cardiovascular risk in women after PE.

Antagonists of the renin-angiotensin-aldosterone system (RAAS), including ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers), may prevent organ failure. We, therefore, investigated whether specific RAAS inhibitors are associated with reduced mortality in patients with sepsis.We conducted a population-based retrospective cohort study using multivariable propensity score-based regression to control for differences among patients using different RAAS inhibitors. A multivariable-adjusted Cox proportional-hazards regression model was used to determine the association between RAAS inhibitors and sepsis outcomes. To directly compare ACEI users, ARB users, and nonusers, a 3-way propensity score matching approach was performed. Results were pooled with previous evidence via a random-effects meta-analysis. A total of 52 727 patients were hospitalized with sepsis, of whom 7642 were prescribed an ACEI and 4237 were prescribed an ARB. Using propensity score-matched analyses, prior ACEI use was associated with decreased 30-day mortality (hazard ratio, 0.84 [95% CI, 0.75-0.94]) and 90-day mortality (hazard ratio, 0.83 [95% CI, 0.75-0.92]) compared with nonuse. Prior ARB use was associated with an improved 90-day survival (hazard ratio, 0.88 [95% CI, 0.83-0.94]). These results persisted in sensitivity analyses focusing on patients without cancer and patients with hypertension. By contrast, no beneficial effect was found for antecedent β-blockers exposure (hazard ratio, 0.99 [95% CI, 0.94-1.05]). The pooled estimates obtained from the meta-analysis was 0.71 (95% CI, 0.58-0.87) for prior use of ACEI/ARB.The short-term mortality after sepsis was substantially lower among those who were already established on RAAS inhibitor treatment when sepsis occurred.

Background Targeted temperature management (TTM) for out-of-hospital cardiac arrest is associated with improved functional survival and is a class I recommendation in resuscitation guidelines. However, patterns of utilization of TTM and adherence to recommended TTM guidelines in contemporary practice are unknown. Methods and Results In a multicenter, prospective cohort of consecutive adults with non-traumatic out-of-hospital cardiac arrest in the Resuscitation Outcomes Consortium in 2012 to 2015, we identified all adults (≥18 years) who were potential candidates for TTM. Of 37 898 out-of-hospital cardiac arrest patients at 186 hospitals across 10 Resuscitation Outcomes Consortium sites, 8313 survived for ≥4 hours after hospital arrival, of which, 2878 (34.6%) received TTM. Mean age was 61.5 years and 36.3% were women. Median hospital rate of TTM use was 27% (interquartile range [IQR]: 14%, 45%), with an over 2-fold difference across sites after accounting for differences in presentation characteristics (median odds ratio, 2.10 [1.83-2.26]). Notably, TTM utilization decreased during the study period (57.5% [2012] to 26.5% [2015], P<0.001) including among shockable out-of-hospital cardiac arrest (73.4% to 46.3%, P<0.001). When administered, the median rate of deviation from one or more recommended practices was 60% (IQR: 40%, 78%). The median rate for delayed onset of TTM was 13% (IQR: 0%, 25%), varying by 70% for identical patients across 2 randomly chosen hospitals (median odds ratio 1.70 [1.39-1.97]). Similarly, the median rate for TTM <24 hours was 20% (IQR: 0%, 34%) and for achieved temperature <32°C was 18% (IQR: 0%, 39%), with marked variation across sites (median odds ratios of 1.44 [1.18-1.64] and 1.98 [1.62-2.31], respectively). Conclusions There has been a substantial decline in the utilization of TTM with significant variation in its real-world implementation. Further standardization of contemporary post-resuscitation practices, like TTM, is critical to ensure that their potential survival benefit is realized.

Background and Purpose- Physiological effects of stroke are best assessed over entire brain networks rather than just focally at the site of structural damage. Resting-state functional magnetic resonance imaging can map functional-anatomic networks by analyzing spontaneously correlated low-frequency activity fluctuations across the brain, but its potential usefulness in predicting functional outcome after acute stroke remains unknown. We assessed the ability of resting-state functional magnetic resonance imaging to predict functional outcome after acute stroke. Methods- We scanned 37 consecutive reperfused stroke patients (age, 69±14 years; 14 females; 3-day National Institutes of Health Stroke Scale score, 6±5) on day 3 after symptom onset. After imaging preprocessing, we used a whole-brain mask to calculate the correlation coefficient matrices for every paired region using the Harvard-Oxford probabilistic atlas. To evaluate functional outcome, we applied the modified Rankin Scale at 90 days. We used region of interest analyses to explore the functional connectivity between regions and graph-computation analysis to detect differences in functional connectivity between patients with good functional outcome (modified Rankin Scale score ≤2) and those with poor outcome (modified Rankin Scale score >2). Results- Patients with good outcome had greater functional connectivity than patients with poor outcome. Although 3-day National Institutes of Health Stroke Scale score was the most accurate independent predictor of 90-day modified Rankin Scale (84.2%), adding functional connectivity increased accuracy to 94.7%. Preserved bilateral interhemispheric connectivity between the anterior inferior temporal gyrus and superior frontal gyrus and decreased connectivity between the caudate and anterior inferior temporal gyrus in the left hemisphere had the greatest impact in favoring good prognosis. Conclusions- These data suggest that information about functional connectivity from resting-state functional magnetic resonance imaging may help predict 90-day stroke outcome.

Giovanni Boccaccio's Decameron contains a novella that details the sudden death of a young man called Gabriotto, including a portrayal of the discomfort that the protagonist experienced and a rudimentary autopsy performed by local physicians. The intriguing description of symptoms and pathologies has made it possible to read a 7-century-old case through the modern clinical lens. Thanks to the medical and philological analysis of the text-despite the vast difference between modern and medieval medicine-2 hypothetical diagnoses have emerged: either an aortic dissection or an atrial myxoma., (© 2016 American Heart Association, Inc.)