Iron serum levels and iron homeostasis parameters in patients with nosocomial pneumonia treated with cefiderocol: post hoc analysis of the APEKS-NP study

Critically ill patients often present with low serum iron levels or anemia. We evaluated the impact of iron levels and iron homeostasis on the efficacy and safety of cefiderocol, an iron-chelator siderophore cephalosporin, in patients with nosocomial pneumonia in a post hoc analysis of the randomized, double-blind, Phase 3 APEKS-NP study (NCT03032380). Patients with Gram-negative nosocomial pneumonia received cefiderocol 2 g, 3-h infusion, q8h, or high-dose, extended-infusion meropenem 2 g, 3-h infusion, q8h, for 7–14 days. Efficacy and safety parameters, including specific iron homeostasis parameters (i.e., hepcidin, iron, total iron binding capacity, transferrin saturation), were analyzed according to baseline iron levels. In the cefiderocol and meropenem arms, 79.1% (117/148) and 83.3% (125/150) randomized patients, respectively, had low baseline serum iron levels. Rates of 14-day (12.3% [14/114] vs 11.6% [14/121]) and 28-day all-cause mortality (20.5% [23/112] vs 19.0% [23/121]), clinical cure (63.2% [72/114] vs 67.2% [82/122]), and microbiological eradication (43.6% [41/94] vs 48.1% [51/106]) at test of cure were similar in cefiderocol vs meropenem arms, respectively. In the overall safety population, rates of anemia-related adverse events were similar (cefiderocol arm 18.2% [27/148], meropenem arm 18.7% [28/150]). Changes from baseline to test of cure in hepcidin, iron, total iron binding capacity, and transferrin saturation were similar between treatment arms. Cefiderocol treatment did not affect iron homeostasis, and its efficacy and safety were not influenced by baseline serum iron levels. Clinicaltrials.gov registration: NCT03032380. Date of registration: 26 January 2017.

Free-water diffusion tensor imaging detects occult periependymal abnormality in the AQP4-IgG-seropositive neuromyelitis optica spectrum disorder

To compare free-water corrected diffusion tensor imaging (DTI) measures in the normal-appearing periependymal area between AQP4-IgG-seropositive NMOSD and multiple sclerosis (MS) to investigate occult pathophysiology. This prospective study included 44 patients (mean age, 39.52 ± 11.90 years; 14 men) with AQP4-IgG-seropositive NMOSD (n = 20) and MS (n = 24) who underwent DTI between April 2014 and April 2020. Based on free-water corrected DTI measures obtained from normal-appearing periependymal voxels of (1) lateral ventricles and (2) the 3rd and 4th ventricles as dependent variables, MANCOVA was conducted to compare the two groups, using clinical variables as covariates. A significant difference was found between AQP4-IgG-seropositive NMOSD and MS in the 3rd and 4th periependymal voxels (λ = 0.462, P = 0.001). Fractional anisotropy, axial diffusivity was significantly decreased and radial diffusivity was increased in AQP4-IgG-seropositive NMOSD in post-hoc analysis, compared with MS (F = 27.616, P < 0.001, F = 7.336, P = 0.011, and F = 5.800, P = 0.022, respectively). Free-water corrected DTI measures differ in the periependymal area surrounding the diencephalon and brain stem/cerebellum between MS and NMOSD, which may suggest occult white matter injury in areas with distribution of AQP-4 in NMOSD.

The impact of the COVID-19 pandemic on non-COVID induced sepsis survival

Background The COVID-19 pandemic has taken a toll on health care systems worldwide, which has led to increased mortality of different diseases like myocardial infarction. This is most likely due to three factors. First, an increased workload per nurse ratio, a factor associated with mortality. Second, patients presenting with COVID-19-like symptoms are isolated, which also decreases survival in cases of emergency. And third, patients hesitate to see a doctor or present themselves at a hospital. To assess if this is also true for sepsis patients, we asked whether non-COVID-19 sepsis patients had an increased 30-day mortality during the COVID-19 pandemic. Methods This is a post hoc analysis of the SepsisDataNet.NRW study, a multicentric, prospective study that includes septic patients fulfilling the SEPSIS-3 criteria. Within this study, we compared the 30-day mortality and disease severity of patients recruited pre-pandemic (recruited from March 2018 until February 2020) with non-COVID-19 septic patients recruited during the pandemic (recruited from March 2020 till December 2020). Results Comparing septic patients recruited before the pandemic to those recruited during the pandemic, we found an increased raw 30-day mortality in sepsis-patients recruited during the pandemic (33% vs. 52%, p = 0.004). We also found a significant difference in the severity of disease at recruitment (SOFA score pre-pandemic: 8 (5 - 11) vs. pandemic: 10 (8 - 13); p < 0.001). When adjusted for this, the 30-day mortality rates were not significantly different between the two groups (52% vs. 52% pre-pandemic and pandemic, p = 0.798). Conclusions This led us to believe that the higher mortality of non-COVID19 sepsis patients during the pandemic might be attributed to a more severe septic disease at the time of recruitment. We note that patients may experience a delayed admission, as indicated by elevated SOFA scores. This could explain the higher mortality during the pandemic and we found no evidence for a diminished quality of care for critically ill sepsis patients in German intensive care units.