Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial.

Background: The evidence base regarding the safety of intravenous (IV) iron therapy in patients with chronic kidney disease (CKD) is incomplete and largely based on small studies of relatively short duration. Methods: FIND-CKD (ClinicalTrials.gov number NCT00994318) was a 1-year, open-label, multicenter, prospective study of patients with nondialysis-dependent CKD, anemia and iron deficiency randomized (1:1:2) to IV ferric carboxymaltose (FCM), targeting higher (400-600 µg/L) or lower (100-200 µg/L) ferritin, or oral iron. A post hoc analysis of adverse event rates per 100 patient-years was performed to assess the safety of FCM versus oral iron over an extended period. Results: The safety population included 616 patients. The incidence of one or more adverse events was 91.0, 100.0 and 105.0 per 100 patient-years in the high ferritin FCM, low ferritin FCM and oral iron groups, respectively. The incidence of adverse events with a suspected relation to study drug was 15.9, 17.8 and 36.7 per 100 patient-years in the three groups; for serious adverse events, the incidence was 28.2, 27.9 and 24.3 per 100 patient-years. The incidence of cardiac disorders and infections was similar between groups. At least one ferritin level ≥800 µg/L occurred in 26.6% of high ferritin FCM patients, with no associated increase in adverse events. No patient with ferritin ≥800 µg/L discontinued the study drug due to adverse events. Estimated glomerular filtration rate remained the stable in all groups. Conclusions: These results further support the conclusion that correction of iron deficiency anemia with IV FCM is safe in patients with nondialysis-dependent CKD

Clinical efficiency of operating room-based sliding gantry CT as compared to mobile cone-beam CT-based navigated pedicle screw placement in 853 patients and 6733 screws

Purpose!#!Multiple solutions for navigation-guided pedicle screw placement are available. However, the efficiency with regard to clinical and resource implications has not yet been analyzed. The present study's aim was to analyze whether an operating room sliding gantry CT (ORCT)-based approach for spinal instrumentation is more efficient than a mobile cone-beam CT (CBCT)-based approach.!##!Methods!#!This cohort study included a random sample of 853 patients who underwent spinal instrumentation using ORCT-based or CBCT-based pedicle screw placement due to tumor, degenerative, trauma, infection, or deformity disorders between November 2015 and January 2020.!##!Results!#!More screws had to be revised intraoperatively in the CBCT group due to insufficient placement (ORCT: 98, 2.8% vs. CBCT: 128, 4.0%; p = 0.0081). The mean time of patients inside the OR (Interval 5 Entry-Exit) was significantly shorter for the ORCT group (ORCT: mean, [95% CI] 256.0, [247.8, 264.3] min, CBCT: 283.0, [274.4, 291.5] min; p < 0.0001) based on shorter times for Interval 2 Positioning-Incision (ORCT: 18.8, [18.1, 19.9] min, CBCT: 33.6, [32.2, 35.5] min; p < 0.0001) and Interval 4 Suture-Exit (ORCT: 24.3, [23.6, 26.1] min, CBCT: 29.3, [27.5, 30.7] min; p < 0.0001).!##!Conclusions!#!The choice of imaging technology for navigated pedicle screw placement has significant impact on standard spine procedures even in a high-volume spine center with daily routine in such devices. Particularly with regard to the duration of surgeries, the shorter time needed for preparation and de-positioning in the ORCT group made the main difference, while the accuracy was even higher for the ORCT

Table_1_Biomarkers for differentiation of coronavirus disease 2019 or extracorporeal membrane oxygenation related inflammation and bacterial/fungal infections in critically ill patients: A prospective observational study.XLSX

Secondary infections in coronavirus disease 2019 (COVID-19) patients are difficult to distinguish from inflammation associated with COVID-19 and/or extracorporeal membrane oxygenation (ECMO). Therefore, highly specific and sensitive biomarkers are needed to identify patients in whom antimicrobial therapy can be safely withheld. In this prospective monocentric study, 66 COVID-19 patients admitted to the intensive care unit (ICU) for ECMO evaluation were included. A total of 46 (70%) patients with secondary infections were identified by using broad microbiological and virological panels and standardized diagnostic criteria. Various laboratory parameters including C-reactive protein (CRP), interleukin (IL)-6, procalcitonin (PCT), and IL-10 were determined at time of study inclusion. The best test performance for differentiating bacterial/fungal secondary infections and COVID-19 and/or ECMO associated inflammation was achieved by IL-10 (ROC-AUC 0.84) and a multivariant step-wise regression model including CRP, IL-6, PCT, and IL-10 (ROC-AUC 0.93). Data obtained in the present study highlights the use of IL-10 to differentiate secondary bacterial/fungal infections from COVID-19 and/or ECMO associated inflammation in severely ill COVID-19 patients.</p

Image_2_Biomarkers for differentiation of coronavirus disease 2019 or extracorporeal membrane oxygenation related inflammation and bacterial/fungal infections in critically ill patients: A prospective observational study.PNG

Secondary infections in coronavirus disease 2019 (COVID-19) patients are difficult to distinguish from inflammation associated with COVID-19 and/or extracorporeal membrane oxygenation (ECMO). Therefore, highly specific and sensitive biomarkers are needed to identify patients in whom antimicrobial therapy can be safely withheld. In this prospective monocentric study, 66 COVID-19 patients admitted to the intensive care unit (ICU) for ECMO evaluation were included. A total of 46 (70%) patients with secondary infections were identified by using broad microbiological and virological panels and standardized diagnostic criteria. Various laboratory parameters including C-reactive protein (CRP), interleukin (IL)-6, procalcitonin (PCT), and IL-10 were determined at time of study inclusion. The best test performance for differentiating bacterial/fungal secondary infections and COVID-19 and/or ECMO associated inflammation was achieved by IL-10 (ROC-AUC 0.84) and a multivariant step-wise regression model including CRP, IL-6, PCT, and IL-10 (ROC-AUC 0.93). Data obtained in the present study highlights the use of IL-10 to differentiate secondary bacterial/fungal infections from COVID-19 and/or ECMO associated inflammation in severely ill COVID-19 patients.</p

Table_2_Biomarkers for differentiation of coronavirus disease 2019 or extracorporeal membrane oxygenation related inflammation and bacterial/fungal infections in critically ill patients: A prospective observational study.DOCX

Secondary infections in coronavirus disease 2019 (COVID-19) patients are difficult to distinguish from inflammation associated with COVID-19 and/or extracorporeal membrane oxygenation (ECMO). Therefore, highly specific and sensitive biomarkers are needed to identify patients in whom antimicrobial therapy can be safely withheld. In this prospective monocentric study, 66 COVID-19 patients admitted to the intensive care unit (ICU) for ECMO evaluation were included. A total of 46 (70%) patients with secondary infections were identified by using broad microbiological and virological panels and standardized diagnostic criteria. Various laboratory parameters including C-reactive protein (CRP), interleukin (IL)-6, procalcitonin (PCT), and IL-10 were determined at time of study inclusion. The best test performance for differentiating bacterial/fungal secondary infections and COVID-19 and/or ECMO associated inflammation was achieved by IL-10 (ROC-AUC 0.84) and a multivariant step-wise regression model including CRP, IL-6, PCT, and IL-10 (ROC-AUC 0.93). Data obtained in the present study highlights the use of IL-10 to differentiate secondary bacterial/fungal infections from COVID-19 and/or ECMO associated inflammation in severely ill COVID-19 patients.</p

Early Aβ reduction prevents progression of cerebral amyloid angiopathy

OBJECTIVE: Clinical trials targeting Aβ for Alzheimer's disease (AD) failed for arguable reasons that include selecting the wrong stages of AD pathophysiology or Aβ being the wrong target at all. Targeting Aβ to prevent cerebral amyloid angiopathy (CAA) has not been rigorously followed although the causal role of Aβ for CAA and related hemorrhages is undisputed. CAA occurs with normal aging and to various degree in AD where its impact and treatment is confounded by the presence of parenchymal Aβ deposition. METHODS: APPDutch mice develop CAA in the absence of parenchymal amyloid, mimicking hereditary cerebral hemorrhage with amyloidosis - Dutch (HCHWA-D). Mice were treated with a BACE1 inhibitor. 3D-ultramicroscopy and immunoassays were used for visualizing CAA and assessing Aβ in CSF and brain. RESULTS: CAA onset in mice was at 22-24 mo of age, first in frontal leptomeningeal and superficial cortical vessels followed by vessels penetrating the cortical layers. CSF Aβ increased with aging followed by a decrease of both, Aβ40 and Aβ42 upon CAA onset supporting that combined reduction of CSF Aβ40 and 42 is a specific biomarker for vascular amyloid. BACE1 inhibitor treatment starting at CAA onset and continued for 4 mo revealed a 90% Aβ reduction in CSF and largely prevented CAA progression and associated pathologies. INTERPRETATION: This is the first study showing that Aβ reduction at early disease time points largely prevents CAA in the absence of parenchymal amyloid. Our observation provides a preclinical basis for Aβ-reducing treatments in patients at risk of CAA and in presymptomatic HCHWA-D. This article is protected by copyright. All rights reserved