Purpose: The DIANA study aimed to evaluate how often antimicrobial de-escalation (ADE) of empirical treatment is performed in the intensive care unit (ICU) and to estimate the effect of ADE on clinical cure on day 7 following treatment initiation. Methods: Adult ICU patients receiving empirical antimicrobial therapy for bacterial infection were studied in a prospective observational study from October 2016 until May 2018. ADE was defined as (1) discontinuation of an antimicrobial in case of empirical combination therapy or (2) replacement of an antimicrobial with the intention to narrow the antimicrobial spectrum, within the first 3 days of therapy. Inverse probability (IP) weighting was used to account for time-varying confounding when estimating the effect of ADE on clinical cure. Results: Overall, 1495 patients from 152 ICUs in 28 countries were studied. Combination therapy was prescribed in 50%, and carbapenems were prescribed in 26% of patients. Empirical therapy underwent ADE, no change and change other than ADE within the first 3 days in 16%, 63% and 22%, respectively. Unadjusted mortality at day 28 was 15.8% in the ADE cohort and 19.4% in patients with no change [p = 0.27; RR 0.83 (95% CI 0.60-1.14)]. The IP-weighted relative risk estimate for clinical cure comparing ADE with no-ADE patients (no change or change other than ADE) was 1.37 (95% CI 1.14-1.64). Conclusion: ADE was infrequently applied in critically ill-infected patients. The observational effect estimate on clinical cure suggested no deleterious impact of ADE compared to no-ADE. However, residual confounding is likely.

Background: While amyloid-β (Aβ) plaques and tau tangles are the well-recognized pathologies of Alzheimer’s disease (AD), they are more often observed in healthy individuals than in AD patients. This discrepancy makes it extremely challenging to utilize these two proteinopathies as reliable biomarkers for the early detection as well as later diagnosis of AD. Objective: We hypothesize and provide preliminary evidence that topographically overlapping Aβ and tau within the default mode network (DMN) play more critical roles in the underlying pathophysiology of AD than each of the tau and/or Aβ pathologies alone. Methods: We used our newly developed quantification methods and publicly available neuroimaging data from 303 individuals to provide preliminary evidence of our hypothesis. Results: We first showed that the probability of observing overlapping Aβ and tau is significantly higher within than outside the DMN. We then showed evidence that using Aβ and tau overlap can increase the reliability of the prediction of healthy individuals converting to mild cognitive impairment (MCI) and to a lesser degree converting from MCI to AD. Finally, we provided evidence that while the initial accumulations of Aβ and tau seems to be started independently in the healthy participants, the accumulations of the two pathologies interact in the MCI and AD groups. Conclusion: These findings shed some light on the complex pathophysiology of AD and suggest that overlapping Aβ and tau pathologies within the DMN might be a more reliable biomarker of AD for early detection and later diagnosis of the disease.

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Objectives One of the most important prognostic factors of cerebral venous sinus thrombosis (CVST) is intracranial hemorrhage (ICH). We studied the risk factors, clinical, and radiologic characteristics of early, delayed, and expanded ICH in Iranian patients with CVST. Materials and Methods In a retrospective study, from August 2012 to September 2016, all adult patients with a confirmed diagnosis of CVST were recruited. Demographic, clinical, and radiologic characteristics of the patients were recorded. The predictors of early, delayed, and expanded ICH were assessed through logistic regression analysis. Results Among 174 eligible patients, 35.1% of the patients had early ICH. Delayed and expanded hemorrhage occurred in 5% and 7.4% of the patients, respectively. Higher age was a risk factor (odds ratio [OR] = 1.038, 95% confidence interval [CI] = 1.008‐1.069), and involvement of multiple sinuses/veins was associated with lower risk of early ICH (OR = 0.432, CI = 0.226‐0.827). The risk of delayed ICH was higher in the patients with early hemorrhage (OR = 4.44, CI: 0.990‐19.94), men (OR = 4.18, CI: 0.919‐19.05), and those with a focal neurologic deficit on admission (OR = 16.05, CI: 1.82‐141.39). Acute onset was the predictor of the expansion of early ICH (OR = 8.92, CI: 1.81‐43.77), whereas female gender‐related conditions were associated with a lower risk of hemorrhage expansion (OR = 0.138, CI: 0.025‐0.770). Administration of anticoagulants was associated with neither delayed (P value = .140) nor expanded hemorrhage (P‐value = .623). Conclusions Male gender, early hemorrhages, acute onset, and presence of focal neurologic deficit are the risk factors for delayed and/or expanded hemorrhages in the patients with CVST.

Endoscopic therapy for LSG-related GSS or leaks with FCSEMS is highly effective and safe.