The impact of the updated EORTC/MSG criteria on the classification of hematological patients with suspected invasive pulmonary aspergillosis

ObjectivesOur aim was to evaluate the effect of the updated European Organization for Research and Treatment of Cancer (EORTC) and Mycoses Study Group 2019 definitions for invasive pulmonary aspergillosis (IPA) on patient classification and the related all-cause 12-week mortality.MethodsIn this retrospective cohort study from our tertiary care centre, we reclassified patients with haematological malignancy who underwent bronchoalveolar lavage between 2014 and 2019 for suspected IPA using the novel EORTC 2019 criteria. We performed receiver operating characteristic curve analysis to define the optimal cut-off for positive PCR and galactomannan and present survival analyses and their possible association with these diagnostic criteria through post hoc comparisons with log rank and Cox regression.ResultsFrom 323 episodes of suspected IPA in 282 patients, 73 were reclassified: 31 (42.5%) from possible to probable IPA, 5 (6.8%) from EORTC criteria not met to probable IPA, and 37 (50.7%) from EORTC criteria not met to possible IPA. Probable IPA increased therefore 11.1% (64/323, 19.8% to 100/323, 30.9%), mostly due to positive PCR (31/36, 86.1%). There was no difference in mortality between newly defined possible and probable IPA (log rank p = 0.950). Mortality was higher in probable cases with lower cycle thresholds (Ct values) versus higher Ct values (p = 0.004). Receiver operating characteristic curve analysis showed an optimal Ct value cut-off of 36.8 with a sensitivity of 75% (95% CI 64.9%–85.1%) and a specificity of 61.7% (95% CI 53.5–69.9) for 12-week mortality.DiscussionThe new EORTC criteria led to 11.1% more probable IPA diagnoses, mostly due to Aspergillus PCR. Restricting positive PCR to below a certain threshold might improve the discrimination of the new EORTC IPA categories for mortality.     

Positive Culture During Reimplantation Increases the Risk of Reinfection in Two-Stage Exchange Arthroplasty Despite Administrating Prolonged Antibiotics: A Retrospective Cohort Study and Meta-Analysis

Background

The significance of a positive culture at reimplantation remains an important topic of consideration given the lack of clear metrics for when reimplantation can be performed. The purpose of this study is thus to investigate the (1) association between a positive culture during reimplantation and failure following 2-stage exchange arthroplasty and the (2) influence of prolonged antibiotics on these patients.

The cultural responsibility of dance movement therapy: philosophical considerations

This paper examines the cultural situation and special responsibility of dance movement therapy, delineating certain philosophical and cultural-theoretical interpretations of the ‘corporeal turn’ and ‘therapeutic turn’ of contemporary culture. It aims to show how dance movement therapy’s theoretical horizon is inseparable from the body-mind integration of contemporary philosophies, and how corporeal turn is present in consumer culture, including some of its destructive forms of idealisation and malign regression. The question of how DMT is able to turn malignant regression to the body into benign regression is addressed, and an analysis of the correlating postmodern idea of resilience is offered. Finally, DMT groups are interpreted as social microcosms, and the way Hungarian psychodynamic movement and dance therapists apply their group therapeutic method for the development of democratic culture in the Civil Group Project is described.     

Sonication of Antibiotic Loaded Cement Spacers: A Valuable Technique for Detection of Infection Persistence in Two-stage Revision for Infected Joint Arthroplasty

We evaluated the diagnostic utility of sonication of antibiotic loaded cement spacers comparing with periprosthetic tissue cultures for the detection of persisting infection in 14 patients undergoing staged procedures. Sonication improved microbial detection of intraoperative cultures from 14.2% to 28.5% (P = 0.481). Routine sonication of spacers is recommended.     

Factors determining phage stability/activity: challenges in practical phage application

Introduction: Phages consist of nucleic acids and proteins that may lose their activity under different physico-chemical conditions. The production process of phage formulations may decrease phage infectivity. Ingredients present in the preparation may influence phage particles, although preparation and storage conditions may also cause variations in phage titer. Significant factors are the manner of phage application, the patient’s immune system status, the type of medication being taken, and diet.

Areas covered: We discuss factors determining phage activity and stability, which is relevant for the preparation and application of phage formulations with the highest therapeutic efficacy. Our article should be helpful for more insightful implementation of clinical trials, which could pave the way for successful phage therapy.

Expert opinion: The number of naturally occurring phages is practically unlimited and phages vary in their susceptibility to external factors. Modern methods offer engineering techniques which should lead to enhanced precision in phage delivery and anti-bacterial activity. Recent data suggesting that phages may also be used in treating nonbacterial infections as well as anti-inflammatory and immunomodulatory agents add further weight to such studies. It may be anticipated that different phage activities could have varying susceptibility to factors determining their actions.     

Development of suspension adapted Vero cell culture process technology for production of viral vaccines

Vero cells are considered as the most widely accepted continuous cell line by the regulatory authorities (such as WHO) for the manufacture of viral vaccines for human use. The growth of Vero cells is anchorage-dependent. Scale-up and manufacturing in adherent cultures are labor intensive and complicated. Adaptation of Vero cells to grow in suspension will simplify subcultivation and process scale-up significantly, and therefore reduce the production cost.Here we report on a successful adaptation of adherent Vero cells to grow in suspension in a serum-free and animal component-free medium (IHM03) developed in-house. The suspension adapted Vero cell cultures in IHM03 grew to similar or better maximum cell density as what was observed for the adherent Vero cells grown in commercial serum-free media and with a cell doubling time of 40–44 h. Much higher cell density (8 × 10⁶ cells/mL) was achieved in a batch culture when three volume of the culture medium was replaced during the batch culture process.Both adherent and suspension Vero cells from various stages were tested for their authenticity using short tandem repeat analysis. Testing result indicates that all Vero cell samples had 100% concordance with the Vero DNA control sample, indicating the suspension cells maintained their genetic stability. Furthermore, suspension Vero cells at a passage number of 163 were assayed for tumorigenicity, and were not found to be tumorigenic.The viral productivity of suspension Vero cells was evaluated by using vesicular stomatitis virus (VSV) as a model. The suspension cell culture showed a better productivity of VSV than the adherent Vero cell culture. In addition, the suspension culture could be infected at higher cell densities, thus improving the volumetric virus productivity. More than one log of increase in the VSV productivity was achieved in a 3L bioreactor perfusion culture infected at a cell density of 6.8 × 10⁶ cells/mL.     

Forced Oxidative Degradation Pathways of the Imidazole Moiety of Daclatasvir

Daclatasvir hydrochloride (DCV) is the active pharmaceutical ingredient of Daklinza, a marketed product for the treatment of hepatitis C viral infection. The intrinsic stability of daclatasvir was evaluated via a forced degradation study. DCV was found to be stable in the solid state. In solution, its carbamate moiety is susceptible to basic hydrolysis, whereas its imidazole is liable to base-mediated autoxidation to form degradants 1 and 3, 7-8, respectively. The imidazole moiety can also be oxidized to form degradants 6-7 in the presence of hydrogen peroxide or azobisisobutyronitrile. The chloro-adduct degradant 9 was also observed in hydrogen peroxide solution. Furthermore, the imidazole moiety is sensitive to photodegradation in solution. Degradants 2-8 were observed in a solution of DCV exposed to high intensity light/UV light; the formation of degradants 2 and 5-8 was postulated through 4 degradation pathways. The degradants 3 and 4 were deemed to be secondary degradants of 7 and 5, respectively.