Excellent piece from Poland - read it - Baxter namedBest to all, do your own homework and seek professional advice on any financial matter > $100 USD or CAD.
This is just the last few paragraphs from the study. It is excellent - IMHEO
Pay attention to the 7.3 - VERY sick group ( EAA over .6 ), VERY good results ( ALl alive at day 28 ). IMHEO once more, this feels much like the phase 2 Euphas group. BEGS the question..
* If it is safe and we can effectively measure success along with both starting and ending points, WHY not many more patients? 11 pateints? WHY not 51 or 101 or 501?
HOW much "proof is the proof"? J. Cretian * small numbers reminds me of tiny focussed financing ( TFF ) being perpetucially broke has it's up$ide...thought for another day ; - )
Here is the last portion of the study -
The Rationale and Current Status of Endotoxin Adsorption in the Treatment of Septic Shock
by
Department of Anaesthesiology and Intensive Therapy, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland
Academic Editors: Karim Bendjelid and Barbara Adamik
Received: 7 December 2021 / Revised: 20 January 2022 / Accepted: 24 January 2022 / Published: 26 January 2022
6. COVID-19 and Endotoxemia
The presence of endotoxemia was demonstrated in patients with COVID-19 pneumonia [
88,
89]. Lipopolysaccharide was speculated to be of lung [
89] or intestinal origin [
88] and may have contributed to the pathogenesis of COVID-19. Of note, the presence of bacterial DNA in serum was detected in 49 of 50 samples from 19 COVID-19 pneumonia patients using the 16S rDNA sequencing method [
88].
Endotoxemia was also observed in 75% of 92 critically ill patients with COVID-19, with only two patients having positive blood cultures for Gram-negative organisms [
90]. Significant endotoxemia was found in a cohort of 22 patients with COVID-19-related pneumonia, together with increased serum zonula occludens-1 levels, a marker of the integrity of the intestinal paracellular barrier, implying that there was intestinal barrier dysfunction and supporting the speculation that bacterial translocation from the gastrointestinal tract may complicate severe COVID-19 and may contribute to the cytokine storm [
88,
91]. In another study, the co-existence of low-grade endotoxemia with enhanced levels of zonulin in patients with COVID-19 was observed, as well as an association with thrombotic events [
92].
Only case reports and case series describing the effects of endotoxin removal in patients with COVID-19 have been published to date; therefore, their results should be treated with caution. In a case series of 12 patients from the EUPHAS 2 registry with COVID-19 and endotoxic shock due to a secondary infection, the PMX HP treatment was associated with organ function recovery, hemodynamic improvement, and a reduction in the EAA level [
93]. Clinical improvement was observed after endotoxin adsorbent therapy in six critically ill patients with COVID-19 and an elevated EAA level. All six patients survived [
94]. PMX HP performed in 12 patients with COVID-19 resulted in a decrease in disease severity in 58.3% of the patients on day 14 after the first treatment. It is noteworthy that a high frequency of clotting of the adsorber was observed [
95].
7. Investigating Aspects of Endotoxin Removal
7.1. Timing of the Initiation of Endotoxin Adsorption
Non-randomized studies that compared an early vs. late initiation of the PMX HP treatment in patients with septic shock found better survival or reduced catecholamine requirements in the early treatment group. The initiation of PMX hemoperfusion within 6, 8, or 9 h after the administration of catecholamine or the diagnosis of septic shock resulted in a more favorable outcome compared to a later initiation [
96,
97,
98]. According to the results of these studies, PMX HP therapy should be performed as early as possible in patients with septic shock, and a delay in PMX HP therapy may contribute to increased mortality [
97].
7.2. Extended Endotoxin Adsorption Treatment
The recommended period for PMX HP treatment is 2 h. In studies where the time of treatment ranged from 8 to 24 h, there were improved hemodynamics and improved pulmonary oxygenation, but no improved mortality was observed [
99,
100,
101].
7.3. Endotoxin Removal Treatment Guided by Measuring the Endotoxin Level
In 11 patients diagnosed with postsurgical sepsis and
who had a high EAA (≥0.6), when the PMX HP treatment was performed and
repeated every 24 h until the EAA was low (<0.4), all patients survived until the 28-day follow-up [
102]. These findings are similar to an observation from the post-hoc analysis of the EUPHRATES trial. A trend toward lower mortality and a significant increase in ventilation-free days was found in patients with septic shock and a greater than median reduction in EAA on day 3 after the PMX HP treatment. The same was true for patients who achieved an EAA of less than 0.65 on day 3 [
103].
The authors of the study suggested that the dosing regimen of PMX therapy should be tailored according to measured endotoxin levels and/or patient’s clinical response, but this hypothesis needs to be validated in a prospective study [
103].
8. Conclusions
Adjuvant therapies have, at most, only a supportive role in the treatment of septic shock. Nevertheless, antibiotics, controlling the source, and organ support remain the mainstays of treating sepsis and septic shock. Endotoxin removal therapy, guided by the blood endotoxin level and applied early in the course of septic shock has the potential to improve organ function and improve survival. The adverse effects of endotoxin in the circulation support the timely removal of endotoxin in the course of sepsis, before the vicious spiral of progression to septic shock, multi-organ failure, or death occurs. Unfortunately, this has not been proven in large, randomized studies. Blood purification therapies need further clinical evaluation and their place in the therapy of sepsis/septic shock has not yet been determined.
Funding
This research received no external funding.
Institutional Review Board Statement
Not applicable.
Informed Consent Statement
Not applicable.
Data Availability Statement
No new data were created or analysed in this study. Data sharing is not applicable to this article.
Conflicts of Interest
Jakub Smiechowicz received speaker and consulting fees from Alteco Medical AB and speaker fees from Baxter. The funders had no role in the writing of the manuscript.