Seraph 100 Microbind Affinity Blood Filter Does Not Clear Antibiotics: An Analysis of Antibiotic Concentration Data from PURIFY-OBS.

INTRODUCTION: Novel hemoperfusion systems are emerging for the treatment of sepsis. These devices can directly remove pathogens, pathogen-associated molecular patterns, cytokines, and other inflammatory markers from circulation. However, significant safety concerns such as potential antibiotic clearance need to be addressed prior to these devices being used in large clinical studies. METHODS: Prospective, observational study of 34 participants undergoing treatment with the Seraph 100® Microbind Affinity Blood Filter (Seraph 100) device at 6 participating sites in the USA. Patients were included for analysis if they had a record of receiving an antibiotic concurrent with Seraph 100 treatment. Patients were excluded if there was missing information for blood flow rate. Blood samples were drawn pre- and post-filter at 1 h and 4 h after treatment initiation. These average pre- and post-filter time-concentration observations were then used to estimate antibiotic clearance in L/h (CLSeraph) due to the Seraph 100 device. RESULTS: Of the 34 participants in the study, 17 met inclusion and exclusion criteria for the antibiotic analysis. Data were obtained for 7 antibiotics (azithromycin, cefazolin, cefepime, ceftriaxone, linezolid, piperacillin, and vancomycin) and one beta-lactamase inhibitor. Mean CLSeraph for the antibiotics investigated ranged from -0.57 to 0.47 L/h. No antibiotic had a CLSeraph statistically significant from 0. DISCUSSION/CONCLUSION: The Seraph 100 did not significantly clear any measured antibiotic in clinical samples. These data give further evidence to suggest that these therapies may be safely administered to critically ill patients and will not impact concentrations of administered antibiotics.

A Multicenter Evaluation of the Seraph 100 Microbind Affinity Blood Filter for the Treatment of Severe COVID-19.

The Seraph100 Microbind Affinity Blood Filter (Seraph 100) (ExThera Medical, Martinez, CA) is an extracorporeal therapy that can remove pathogens from blood, including severe acute respiratory syndrome coronavirus 2. The aim of this study was to evaluate safety and efficacy of Seraph 100 treatment for COVID-19. DESIGN: Retrospective cohort study. SETTING: Nine participating ICUs. PATIENTS: COVID-19 patients treated with Seraph 100 (n = 53) and control patients matched by study site (n = 53). INTERVENTION: Treatment with Seraph 100. MEASUREMENTS AND MAIN RESULTS: At baseline, there were no differences between the groups in terms of sex, race/ethnicity, body mass index, and need for mechanical ventilation. However, patients in the Seraph 100 group were younger (median age, 54 yr; interquartile range [IQR], 41-65) compared with controls (median age, 64 yr; IQR, 56-69; p = 0.009). Charlson comorbidity index scores were lower in the Seraph 100 group (2; IQR, 0-3) compared with the control group (3; IQR, 2-4; p = 0.006). Acute Physiology and Chronic Health Evaluation II scores were also lower in Seraph 100 subjects (12; IQR, 9-17) compared with controls (16; IQR, 12-21; p = 0.011). The Seraph 100 group had higher vasopressor-free days with an incidence rate ratio of 1.30 on univariate analysis. This difference was not significant after adjustment. Seraph 100-treated subjects were less likely to die compared with controls (32.1% vs 64.2%; p = 0.001), a difference that remained significant after adjustment. However, no difference in mortality was observed in a post hoc analysis utilizing an external control group. In the full cohort of 86 treated patients, there were 177 total treatments, in which only three serious adverse events were recorded. CONCLUSIONS: Although this study did not demonstrate consistently significant clinical benefit across all endpoints and comparisons, the findings suggest that broad spectrum, pathogen agnostic, blood purification can be safely deployed to meet new pathogen threats while awaiting targeted therapies and vaccines.

Chronic Kidney Disease: Detection and Evaluation.

Chronic kidney disease affects 47 million people in the United States and is associated with significant health care costs, morbidity, and mortality. Because this disease can silently progress to advanced stages, early detection is critical for initiating timely interventions. Multiple guidelines recommend at least annual screening with serum creatinine, urine albumin/creatinine ratio, and urinalysis for patients with risk factors, particularly diabetes mellitus, hypertension, and a history of cardiovascular disease. The U.S. Preventive Services Task Force found insufficient evidence to assess the balance of benefits and harms of screening for chronic kidney disease in the general population, and the American College of Physicians recommends against screening asymptomatic adults without risk factors. Persistently elevated serum creatinine and albuminuria are diagnostic and prognostic hallmarks of chronic kidney disease. Lower levels of albuminuria are associated with adverse renal and cardiovascular outcomes. Serum cystatin C is a novel biomarker that is most useful when a false-positive decreased estimated glomerular filtration rate calculated from serum creatinine is suspected. New guidelines incorporate albuminuria into the classification framework for chronic kidney disease and elaborate on identification of the disease, the frequency of follow-up, and recommendations for nephrology referral. Nephrology consultation is indicated for patients with an estimated glomerular filtration rate less than 30 mL per minute per 1.73 m2, persistent urine albumin/creatinine ratio greater than 300 mg per g or urine protein/creatinine ratio greater than 500 mg per g, or if there is evidence of a rapid loss of kidney function. A multidisciplinary approach between primary care physicians, nephrologists, and other subspecialists for implementing early interventions, providing education, and planning for advanced renal disease is key for effective management.

Cost-Utility Analysis of Mycophenolate Mofetil versus Azathioprine Based Regimens for Maintenance Therapy of Proliferative Lupus Nephritis.

Background/Aims. We aimed to examine the cost-effectiveness of mycophenolate mofetil (MMF) and azathioprine (AZA) as maintenance therapy for patients with Class III and Class IV lupus nephritis (LN), from a United States (US) perspective. Methods. Using a Markov model, we conducted a cost-utility analysis from a societal perspective over a lifetime horizon. The modeled population comprised patients with proliferative LN who received maintenance therapy with MMF (2 gm/day) versus AZA (150 mg/day) for 3 years. Risk estimates of clinical events were based on a Cochrane meta-analysis while costs and utilities were retrieved from other published sources. Outcome measures included costs, quality-adjusted life-years (QALY), incremental cost-effectiveness ratios (ICER), and net monetary benefit. Results. The base-case model showed that, compared with AZA strategy, the ICER for MMF was $2,630,592/QALY at 3 years. Over the patients' lifetime, however, the ICER of MMF compared to AZA was $6,454/QALY. Overall, the ICER results from various sensitivity and subgroup analyses did not alter the conclusions of the model simulation. Conclusions. In the short term, an AZA-based regimen confers greater value than MMF for the maintenance therapy of proliferative LN. From a lifelong perspective, however, MMF is cost-effective compared to AZA.

P2 receptor regulation of [Ca2+]i in cultured mouse mesangial cells.

Experiments were performed to establish the pharmacological profile of purinoceptors and to identify the signal transduction pathways responsible for increases in intracellular calcium concentration ([Ca(2+)](i)) for cultured mouse mesangial cells. Mouse mesangial cells were loaded with fura 2 and examined using fluorescent spectrophotometry. Basal [Ca(2+)](i) averaged 102 +/- 2 nM (n = 346). One hundred micromolar concentrations of ATP, ADP, 2',3'-(benzoyl-4-benzoyl)-ATP (BzATP), ATP-gamma-S, and UTP in normal Ca(2+) medium evoked peak increases in [Ca(2+)](i) of 866 +/- 111, 236 +/- 18, 316 +/- 26, 427 +/- 37, and 808 +/- 73 nM, respectively. UDP or 2-methylthio-ATP (2MeSATP) failed to elicit significant increases in [Ca(2+)](i), whereas identical concentrations of adenosine, AMP, and alpha,beta-methylene ATP (alpha,beta-MeATP) had no detectable effect on [Ca(2+)](i). Removal of Ca(2+) from the extracellular medium had no significant effect on the peak increase in [Ca(2+)](i) induced by ATP, ADP, BzATP, ATP-gamma-S, or UTP compared with normal Ca(2+); however, Ca(2+)-free conditions did accelerate the rate of decline in [Ca(2+)](i) in cells treated with ATP and UTP. [Ca(2+)](i) was unaffected by membrane depolarization with 143 mM KCl. Western blot analysis for P2 receptors revealed expression of P2X(2), P2X(4), P2X(7), P2Y(2), and P2Y(4) receptors. No evidence of P2X(1) and P2X(3) receptor expression was detected, whereas RT-PCR analysis reveals mRNA expression for P2X(1), P2X(2), P2X(3), P2X(4), P2X(7), P2Y(2), and P2Y(4) receptors. These data indicate that receptor-specific P2 receptor activation increases [Ca(2+)](i) by stimulating calcium influx from the extracellular medium and through mobilization of Ca(2+) from intracellular stores in cultured mouse mesangial cells.