Prevalence of Linda Virus Neutralizing Antibodies in the Austrian Pig Population

A novel pestivirus species, termed Lateral-shaking Inducing Neuro-Degenerative Agent virus (LindaV), was discovered in a piglet-producing farm in Austria in 2015 related to severe congenital tremor cases. Since the initial outbreak LindaV has not been found anywhere else. In this study, we determined the seroprevalence of LindaV infections in the domestic pig population of Austria. A fluorophore labeled infectious cDNA clone of LindaV (mCherry-LindaV) was generated and used in serum virus neutralization (SVN) assays for the detection of LindaV specific neutralizing antibodies in porcine serum samples. In total, 637 sera from sows and gilts from five federal states of Austria, collected between the years 2015 and 2020, were analyzed. We identified a single serum showing a high neutralizing antibody titer, that originated from a farm (Farm S2) in the proximity of the initially affected farm. The analysis of 57 additional sera from Farm S2 revealed a wider spread of LindaV in this pig herd. Furthermore, a second LindaV strain originating from this farm could be isolated in cell culture and was further characterized at the genetic level. Possible transmission routes and virus reservoir hosts of this emerging porcine virus need to be addressed in future studies.     

Targeting prostate cancer: Prostate-specific membrane antigen based diagnosis and therapy

The high incidence rates of prostate cancer (PCa) raise demand for improved therapeutic strategies. Prostate tumors specifically express the prostate-specific membrane antigen (PSMA), a membrane-bound protease. As PSMA is highly overexpressed on malignant prostate tumor cells and as its expression rate correlates with the aggressiveness of the disease, this tumor-associated biomarker provides the possibility to develop new strategies for diagnostics and therapy of PCa. Major advances have been made in PSMA targeting, ranging from immunotherapeutic approaches to therapeutic small molecules. This review elaborates the diversity of PSMA targeting agents while focusing on the radioactively labeled tracers for diagnosis and endoradiotherapy. A variety of radionuclides have been shown to either enable precise diagnosis or efficiently treat the tumor with minimal effects to nontargeted organs. Most small molecules with affinity for PSMA are based on either a phosphonate or a urea-based binding motif. Based on these pharmacophores, major effort has been made to identify modifications to achieve ideal pharmacokinetics while retaining the specific targeting of the PSMA binding pocket. Several tracers have now shown excellent clinical usability in particular for molecular imaging and therapy as proven by the efficiency of theranostic approaches in current studies. The archetypal expression profile of PSMA may be exploited for the treatment with alpha emitters to break radioresistance and thus to bring the power of systemic therapy to higher levels.     

Efficacy and safety of adenosine in the treatment of supraventricular tachycardia in infants and children.

One hundred and seventeen episodes of supraventricular tachycardia in 50 children, including 28 infants, were treated with intravenous adenosine. Adenosine was prepared in a sterile solution of 0.9% saline (1 mg/ml) and given in incremental doses of 0.05 mg/kg every two minutes to a maximum of 0.25 mg/kg. Ninety of the 117 episodes were terminated. This included 88 of the 102 episodes of junctional tachycardia (79 of the 92 episodes of atrioventricular reentry tachycardia, seven of the eight episodes of atrioventricular nodal reentry tachycardia, and both of the episodes of long R-P' tachycardia). Only one of four episodes of His bundle tachycardia and one of the eight episodes of ectopic atrial tachycardia were terminated. None of the three episodes of atrial flutter were terminated. Side effects were frequent but mild and included transient complete atrioventricular block (less than 6 s), sinus bradycardia (less than 40 s), ventricular extrasystoles, flushing, nausea, headache, and respiratory disturbance. Reinitiation (within 5 s) of supraventricular tachycardia occurred in 13 of the terminated episodes. Although reinitiation limited its clinical efficacy in some patients, intravenous adenosine offered a safe and efficient method of rapid termination of most episodes of supraventricular tachycardia and in some cases facilitated diagnosis of the mechanism.     

Reduced prevalence of Plasmodium falciparum infection and of concomitant anaemia in pregnant women with heterozygous G6PD deficiency

Glucose-6-phosphate dehydrogenase (G6PD) deficiency confers protection against malaria in children, yet its role in malaria in pregnancy is unknown. In a cross-sectional study among 529 pregnant Ghanaian women, Plasmodium falciparum infection, anaemia and G6PD genotypes were assessed. Of these, 30.4% were heterozygous and 2.6% were homozygous for G6PD deficiency. The prevalence of P. falciparum infection decreased from 66% in G6PD-normal women to 58% in heterozygotes, and to 50% in individuals with homozygous G6PD deficiency (Chi2(trend) = 4.4, P = 0.04). Multivariate analysis revealed that in multigravid women but not in primigravidae, heterozygous G6PD deficiency was associated with a reduced risk of P. falciparum infection (Odds ratio (OR), 0.6; 95% confidence interval (95% CI), [0.4-0.9]). This protection against infection was limited to the third trimenon of pregnancy. In addition, heterozygous G6PD deficiency was associated with a reduced risk of anaemia among infected multigravidae (OR, 0.5 [0.3-1.0]). Pregnancy is a period of high vulnerability to malaria. The results of this study provide evidence for protection against malaria in pregnancy caused by heterozygous G6PD deficiency. This advantage, even if confined to multigravid women, may contribute to the selection of G6PD variants in malaria-endemic regions.     

Pembrolizumab with R-CHOP in previously untreated diffuse large B-cell lymphoma: potential for biomarker driven therapy

Tumor programmed death-ligand 1 (PD-L1) expression in diffuse large B-cell lymphoma (DLBCL) is associated with inferior outcomes. The first-line immunologically-replete setting may be an opportune time for PD-1 inhibition. We evaluated pembrolizumab in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in untreated patients with DLBCL. Eligible patients were age 18 or older, had adequate organ function, and had DLBCL requiring full-course therapy. Patients received pembrolizumab 200 mg/cycle with R-CHOP, primarily to assess toxicity. Response assessment utilized standard criteria, and PD-L1 staining was performed at a validated central laboratory. Among 30 patients, toxicity was comparable to standard R-CHOP but with two grade ≥3 immune related adverse events (rash, pneumonitis). The overall and complete response rate was 90% and 77%. With 25·5 months of median follow-up, 2-year progression-free survival (PFS) is 83%. PD-L1 expression was associated with non-GCB subtype, and improved PFS and survival. Pembrolizumab can safely be added to R-CHOP, and is associated with a high CR rate and 2-year PFS. Improved PFS with PR-CHOP in PD-L1 expressing tumors contradicts historical data in R-CHOP treated patients, supporting evaluation of PD-L1 as a biomarker to identify DLBCL patients who may benefit from this first-line strategy.