Poke Weed Mitogen Requires Toll-Like Receptor Ligands for Proliferative Activity in Human and Murine B Lymphocytes

Poke weed mitogen (PWM), a lectin purified from Phytolacca americana is frequently used as a B cell-specific stimulus to trigger proliferation and immunoglobulin secretion. In the present study we investigated the mechanisms underlying the B cell stimulatory capacity of PWM. Strikingly, we observed that highly purified PWM preparations failed to induce B cell proliferation. By contrast, commercially available PWM preparations with B cell activity contained Toll-like receptor (TLR) ligands such as TLR2-active lipoproteins, lipopolysaccharide and DNA of bacterial origin. We show that these microbial substances contribute to the stimulatory activity of PWM. Additional experimental data highlight the capacity of PWM to enable B cell activation by immunostimulatory DNA. Based on these findings we propose that the lectin sensitizes B cells for TLR stimulation as described for B cell receptor ligation and that B cell mitogenicity of PWM preparations results from synergistic activity of the poke weed lectin and microbial TLR ligands present in the PWM preparations

Driving change in dtap batch release testing

The complexity of vaccine manufacturing has raised the need to drive standardization and quality control requirements as well as batch release of vaccines. The purpose of release testing is to ensure that efficacy and safety of the vaccine product are maintained in all batches. Classical testing includes challenge experiments in animals that provide proof of vaccine potency and identify subpotent vaccines. However, novel concepts such as “consistency testing” question the continued need for in vivo experiments and propose to implement rigorous QC for lot-to-lot consistency testing with other methods at an earlier stage. Please click Download on the upper right corner to see the full abstract

A 5-year look-back at the notification and management of vaccine supply shortages in Germany

Background: Unavailability of vaccines endangers the overall goal to protect individuals and whole populations against infections. Methods: The German notification system includes the publication of vaccine supply shortages reported by marketing authorisation holders (MAH), information on the availability of alternative vaccine products, guidance for physicians providing vaccinations and an unavailability reporting tool to monitor regional distribution issues. Aim: This study provides a retrospective analysis of supply issues and measures in the context of European and global vaccine supply constraints. Results: between October 2015 and December 2020, the 250 notifications concerned all types of vaccines (54 products). Most shortages were caused by increased demand associated with immigration in Germany in 2015 and 2016, new or extended vaccine recommendations, increased awareness, or changes in global immunisation programmes. Shortages of a duration up to 30 days were mitigated using existing storage capacities. Longer shortages, triggered by high demand on a national level, were mitigated using alternative products and re-allocation; in a few cases, vaccines were imported. However, for long lasting supply shortages associated with increased global demand, often occurring in combination with manufacturing issues, few compensatory mechanisms were available. Nevertheless, only few critical incidents were identified: (i) shortage of hexavalent vaccines endangering neonatal immunisation programmes in 2015;(ii) distribution issues with influenza vaccines in 2018; and (iii) unmet demand for pneumococcal and influenza vaccines during the coronavirus disease (COVID)-19 pandemic. Conclusion: Vaccine product shortages in Germany resemble those present in neighbouring EU states and often reflect increased global demand not matched by manufacturing capacities.Peer Reviewe

Impact of rifaximin on the frequency and characteristics of spontaneous bacterial peritonitis in patients with liver cirrhosis and ascites

BACKGROUND: Rifaximin is a non-absorbable antibiotic used to prevent relapses of hepatic encephalopathy which may also be a candidate for prophylaxis of spontaneous bacterial peritonitis (SBP). AIM: To detect the impact of rifaximin on the occurrence and characteristics of SBP. METHODS: We prospectively studied all hospitalized patients that underwent a diagnostic paracentesis in our department from March 2012 to April 2013 for SBP and recorded all clinical data including type of SBP prophylaxis, prior use of rifaximin, concomitant complications of cirrhosis, as well as laboratory results and bacteriological findings. Patients were divided into the following three groups: no antibiotic prophylaxis, prophylaxis with rifaximin or with systemically absorbed antibiotic prophylaxis. RESULTS: Our study cohort comprised 152 patients with advanced liver cirrhosis, 32 of whom developed SBP during the study period. As expected, our study groups differed regarding a history of hepatic encephalopathy and SBP before inclusion into the study. None of the 17 patients on systemic antibiotic prophylaxis developed SBP while 8/27 patients on rifaximin and 24/108 without prophylaxis had SBP (p = 0.02 and p = 0.04 versus systemic antibiotics, respectively). In general, episodes of SBP were similar for patients treated with rifaximin and those without any prophylaxis. However, Escherichia coli and enterococci were dominant in the ascites of patients without any prophylaxis, while mostly klebsiella species were recovered from the ascites samples in the rifaximin group. CONCLUSION: Rifaximin pretreatment did not lead to a reduction of SBP occurrence in hospitalized patients with advanced liver disease. However, the bacterial species causing SBP were changed by rifaximin

Adjuvant Use of Ivabradine in Acute Heart Failure due to Myocarditis

We report two cases of young men in whom acute heart failure due to myocarditis was diagnosed. The patients had been transferred to the intensive care unit (ICU) with commencing symptoms of acute heart failure and consecutive multiorgan failure for further treatment and to evaluate the indication for implantation of a ventricular assist device or for high urgent orthotopic heart transplantation. In both patients, the If-channel inhibitor ivabradine was administered off-label to provide selective heart rate reduction, and thus support hemodynamic stabilization. Though currently considered off-label use in patients suffering from severe hypotension and acute heart failure, the use of ivabradine may beneficially influence outcome by allowing optimization of the patient's heart rate concomitant to initial measures of clinical stabilization