Safety and Efficacy of Ferric Carboxymaltose in Heart Failure With Preserved Ejection Fraction and Iron Deficiency.

Heart Failure with Preserved Ejection Fraction (HFpEF) is a prevalent cardiovascular condition characterized by a complex pathophysiology and limited therapeutic options. Coinciding iron deficiency often compounds the clinical picture, contributing to symptom burden and adverse outcomes. The review underscores the urgency for effective treatments in light of its increasing incidence and considerable healthcare burden. It highlights the clinical significance of addressing iron deficiency in HFpEF patients. FCM emerges as a promising therapeutic modality, demonstrating the ability to rapidly restore iron stores and enhance patients' quality of life while reducing hospitalization rates and mortality. The review thoroughly elucidates the impact of iron deficiency on HFpEF symptoms and outcomes, elucidating how FCM effectively mitigates these challenges. Detailed discussions encompass FCM's mechanism of action, pharmacokinetics, and safety profile. Notably, FCM's adaptability to diverse patient profiles and clinical settings is emphasized, reinforcing its clinical utility. Clinical evidence, including study designs, patient cohorts, and key findings, affirms FCM's potential as a valuable therapeutic option. Real-world data analysis further underscores FCM's practicality and safety beyond controlled clinical trials. The review concludes by addressing future research directions and critical research gaps, accentuating the need for mechanistic insights, long-term outcome studies, and refined patient selection criteria. As FCM increasingly integrates into clinical practice, it offers promise in revolutionizing HFpEF management, addressing an unmet need in this intricate cardiovascular condition.

Utility of Cerebral Embolic Protection Devices in Transcatheter Procedures: A Systematic Review and Meta-Analysis.

With the emergence of the largest randomized control trial to date-the Stroke Protection With Sentinel During Transcatheter Aortic Valve Replacement (PROTECTED TAVR) study-we sought to conduct an updated meta-analyses to evaluate the utility of CEP devices on both clinical outcomes and neuroimaging parameters. Electronic databases were queried through November 2022 for clinical trials comparing the utility of Cerebral Embolic Protection (CEP) devices in Transcatheter Aortic Valve Replacement (TAVR) with non-CEP TAVR procedures. Meta-analyses were performed using the generic inverse variance technique, and a random-effects model, and results are presented as weighted mean differences (WMD) for continuous outcomes, and hazard ratios (HR) for dichotomous outcomes. Outcomes of interest included stroke, disabling stroke, nondisabling stroke, bleeding, mortality, vascular complications, new ischemic lesions, acute kidney injury (AKI), and total lesion volume. Thirteen studies (8 RCTs, 5 observational studies) consisting of 128,471 patients were included in the analysis. Results from our meta-analyses showed a significant reduction in stroke (OR: 0.84 [0.74-0.95]; P < 0.01; I2 = 0%), disabling stroke (OR: 0.37 [0.21-0.67]; P < 0.01; I2 = 0%) and bleeding events (OR: 0.91 [0.83-0.99]; P = 0.04; I2 = 0%) through CEP device use in TAVR. The use of CEP devices had no significant impact on nondisabling stroke (OR: 0.94 [0.65-1.37]; P < 0.01; I2 = 0%), mortality (OR: 0.78 [0.53-1.14]; P < 0.01; I2 = 17%), vascular complications (OR: 0.99 [0.63-1.57]; P < 0.01; I2 = 28%), AKI (OR: 0.78 [0.46-1.32]; P < 0.01; I2 = 0%), new ischemic lesions (MD: -1.72 [-4.01, 0.57]; P < 0.001; I2 = 95%) and total lesion volume (MD: -46.11 [-97.38, 5.16]; P < 0.001; I2 = 81%). The results suggest that CEP device use was associated with a lower risk of disabling stroke and bleeding events in patients undergoing TAVR.

Relationship of basal heart rate variability to in vivo cytokine responses after endotoxin exposure.

Autonomic inputs from the sympathetic and parasympathetic nervous systems, as measured by heart rate variability (HRV), have been reported to correlate to the severity injury and responses to infectious challenge among critically ill patients. In addition, parasympathetic/vagal activity has been shown experimentally to exert anti-inflammatory effects via attenuation of splanchnic tissue TNF-alpha production. We sought to define the influence of gender on HRV responses to in vivo endotoxin challenge in healthy humans and to determine if baseline HRV parameters correlated with endotoxin-mediated circulating cytokine responses. Young (<30 years of age), healthy subjects (n = 30) received endotoxin (2 ng/kg), and HRV and blood samples were obtained serially thereafter. Plasma cytokines were measured by enzyme-linked immunosorbent assay, and HRV parameters were determined by analysis of serial 5-min epochs of heart rate monitoring. In addition, calculation of multiscale entropy deriving from cardiac monitoring data was performed. The influence of factors such as gender, body mass index, and resting heart rate on HRV after endotoxin exposure was assessed. We found that gender, body mass index, or resting heart rate did not significantly alter the HRV response after endotoxin exposure. Using entropy analysis, we observed that females had significantly higher entropy values at 24 h after endotoxin exposure. Using a serially sampling protocol for cytokine determination, we found a significant correlation of several baseline HRV parameters (percentage of interval differences of successive interbeat intervals more than 50 ms, r = 0.42, P < 0.05; high-frequency variability, r = 0.4, P < 0.05; and low-frequency/high-frequency ratio, r = -0.43, P < 0.05) on TNF-alpha release after endotoxin exposure.

Influence of acute epinephrine infusion on endotoxin-induced parameters of heart rate variability: a randomized controlled trial.

OBJECTIVE: To determine whether the acute anti-inflammatory influence of epinephrine (EPI) extends to changes in heart rate variability (HRV) induced by the prototypical inflammatory stimulus, endotoxin (lipopolysaccharide [LPS]). SUMMARY BACKGROUND DATA: HRV reflects fluctuating cardiac autonomic inputs and is acutely reduced during the systemic inflammation induced by LPS as well as during severe critical illnesses such as sepsis and traumatic injury. While EPI may diminish proinflammatory cytokine release, it is unknown whether this net anti-inflammatory activity extends to HRV. METHODS: Healthy volunteers (n = 17) were randomized to either saline + LPS (2 ng/kg) or LPS + antecedent EPI infusion (30 ng/kg/min) from -3 to 6 hours relative to LPS. HRV and blood samples were obtained before EPI and LPS as well as hourly afterward. Plasma cytokines were measured by ELISA. Statistical analysis was by repeated measures analysis of variance. This study was registered at Clinicaltrials.gov and is listed under the following ID number: NCT00753402. RESULTS: LPS acutely influenced all measured parameters of HRV including standard deviation of the average beat to beat intervals over a 5-minute period, percentage of interval differences of successive interbeat intervals greater than 50 milliseconds and square root of the mean squared differences, high frequency (HF), low frequency, low frequency/HF, and very low frequency (all P < 0.01). EPI infusion reduced the inflammatory cytokine response to LPS as measured by decreased TNFalpha, IL-6, and IL-8 (P < 0.01). Relative to the saline + LPS group, antecedent EPI infusion was associated with further reductions in parameters of HRV measuring vagal/parasympathetic activity including, percentage of interval differences of successive interbeat intervals greater than 50 milliseconds, square root of the mean squared differences, and HF (P < 0.05). CONCLUSION: Prior EPI exposure exerts anti-inflammatory influences but also may reduce vagus nerve activity. Hence, acute EPI administration may be protective against early inflammatory challenges but diminish vagal nerve responsiveness to subsequent stimuli.

Reduction of Cr(VI) and bioaccumulation of chromium by gram positive and gram negative microorganisms not previously exposed to Cr-stress.

Resistance to Cr(VI) is usually associated with its cellular exclusion, precluding enrichment techniques for the isolation of organisms accumulating Cr(VI) via bioreduction to insoluble Cr(III). A technique was developed to screen for potential Cr(VI) reduction in approx. 2000 isolates from a coastal environment, based on the non-specific reduction of selenite and tellurite to Se0 and Te0, and reduction of tetrazolium blue to insoluble blue formazan. The most promising strains were further screened in liquid culture, giving three, which were identified by 16S rRNA sequence analysis as Bacillus pumilus, Exiguobacterium aurantiacum and Pseudomonas synxantha, all of which reduced 100 microM Cr(VI) anaerobically, without growth. The respective removal of Cr(VI) was 90% and 80% by B. pumilus and E. aurantiacum after 48 h and 80% and by P. synxantha after 192 h. With the gram positive strains Cr(VI) promoted loss of flagella and, in the case of B. pumilus, lysis of some cells, but Cr was deposited as an exocellular precipitate which was identified as containing Cr and P using energy dispersive X-ray microanalysis (EDAX). This prompted the testing of Citrobacter sp. N14 (subsequently re-assigned by 16S rRNA sequence analysis and biochemical studies as a strain of Serratia) which bioprecipitates metal cation phosphates via enzymatically-liberated phosphate. This strain reduced Cr(VI) at a rate comparable to that of P. synxantha but Cr(III) was not bioprecipitated where La(III) was removed as LaPO4, even though a similar amount of phosphate was produced in the presence of Cr(III). Since B. pumilus removed most of the Cr(VI), with the formation of cell-bound CrPO4 implicated, this suggests that this strain could have future bioprocess potential.

Biosorption of copper by a bacterial biofilm on a flexible polyvinyl chloride conduit.

Inexpensive technologies with less-than-optimal efficiencies as a strategy for countering economic restraints to pollution control have been evaluated by using a laboratory-scale biotreatment process for copper-containing effluent. Economizing measures include the use of polyvinyl chloride (PVC) cylinders fashioned from commercially available flexible PVC conduit to support a biofilm that was cultured in an inexpensive medium prepared in wastewater. The biofilm was challenged by aqueous copper solution in a bioreactor and subsequently analyzed under a scanning electron microscope with energy-dispersive X-ray microanalysis.