Effects of sub-lethal doses of nisin on the virulence of Salmonella enterica in Galleria mellonella larvae

Salmonella enterica is a pathogen that induces self-limiting gastroenteritis and is of worldwide concern. Nisin, an antimicrobial peptide, has emerged as an alternative for the control of microbial growth but its effect on the virulence of pathogenic bacteria is not yet well-explored. This work aimed to evaluate the virulence of S. enterica in the presence of sub-inhibitory nisin using the experimental model Galleria mellonella. Sub-inhibitory concentrations of nisin of 11.72 and 46.88 μM did not affect the cellular viability of S. enterica but promoted changes in gene expression within 1 h of treatment, with increases of up to 3-fold of pagC, 1.8-fold of invA and 2.3-fold of invF. Larvae of G. mellonella inoculated with S. enterica combined with nisin at 46.88 μM presented mortality, and TL₅₀ noticeably increased to 50% and 80% at 24 and 48 h post-infection, respectively. Defence responses, such as melanisation, nodulation, pseudopodia, immune response, and expression of defence proteins of the larvae G. mellonella were enhanced when the treatments with S. enterica were combined with 11.72 or 46.88 μM nisin. These results show an increase in virulence of S. enterica by sub-MIC concentration of nisin that needs to be explored.     

Establishment of a cell processing laboratory to support hematopoietic stem cell transplantation and chimeric antigen receptor (CAR)-T cell therapy

Cell processing laboratories are an important part of cancer treatment centers. Cell processing laboratories began by supporting hematopoietic stem cell (HSC) transplantation programs. These laboratories adapted closed bag systems, centrifuges, sterile connecting devices and other equipment used in transfusion services/blood banks to remove red blood cells and plasma from marrow and peripheral blood stem cells products. The success of cellular cancer immunotherapies such as Chimeric Antigen Receptor (CAR) T-cells has increased the importance of cell processing laboratories. Since many of the diseases successfully treated by CAR T-cell therapy are also treated by HSC transplantation and since HSC transplantation teams are well suited to manage patients treated with CAR T-cells, many cell processing laboratories have begun to produce CAR T-cells. The methods that have been used to process HSCs have been modified for T-cell enrichment, culture, stimulation, transduction and expansion for CAR T-cell production. While processing laboratories are well suited to manufacture CAR T-cells and other cellular therapies, producing these therapies is challenging. The manufacture of cellular therapies requires specialized facilities which are costly to build and maintain. The supplies and reagents, especially vectors, can also be expensive. Finally, highly skilled staff are required. The use of automated equipment for cell production may reduce labor requirements and the cost of facilities. The steps used to produce CAR T-cells are reviewed, as well as various strategies for establishing a laboratory to manufacture these cells.     

The role of FDG-PET-CT is limited in initial staging of nodal metastasis for thin cutaneous melanoma

IntroductionPositron emission tomography computed tomography (PET-CT) is often used to stage nodal metastases in thin cutaneous melanoma, with limited evidence.MethodsA retrospective review of patients with cutaneous malignant melanoma treated at our institution was performed from 2005 to 2015, identifying those who received a PET-CT prior to lymphadenectomy. Biopsy features, lymph node status, and PET-CT results were collected. We calculated the overall sensitivity, specificity, accuracy, likelihood ratios, and positive predictive value of PET-CT in identifying nodal metastases. Results were stratified by initial biopsy tumor depth.ResultsWe identified 367 cases; 95 obtained a PET-CT prior to lymphadenectomy. Overall, sensitivity and specificity of PET-CT was 34.6% and 95.4%, respectively. The positive likelihood ratio and negative likelihood ratio were 7.62 and 0.68, respectively. The accuracy was 78.2%. The positive predictive value for T3 and T4 melanomas were 100% and 81.4%, respectively. For thin melanomas, specificity and accuracy was 88.2% and 88.2%, respectively.ConclusionsPET-CT has low specificity and its use alone is not recommended for initial staging of nodal metastases in thin cutaneous malignant melanoma.     

Evaluation of spin in the abstracts of orthopedic trauma literature: A cross-sectional review

ObjectivesA cross-sectional analysis of orthopedic trauma randomized controlled trial (RCT) abstracts to assess the frequency and manifestations of spin, the misrepresentation or distortion of research findings, in orthopedic trauma clinical trials.MethodsThe top 5 orthopedic trauma journals were searched from January 1, 2012, to December 31, 2017. RCTs with nonsignificant endpoints (p > .05) were analyzed for spin in the abstract. The primary endpoint of our investigation was the frequency and type of spin. The secondary endpoint was to assess whether funding source was associated with the presence of spin. Due to the low reporting of funding sources no statistics were able to be computed for this outcome.ResultsOur PubMed search yielded 517 articles. Primary screening excluded 303 articles, and full text evaluation excluded an additional 161. Overall, 53 articles were included. Spin was identified in 35 of the 53 (66.0%) abstracts analyzed. Evidence of spin was found in 21 (39.6%) abstract results sections and 22 (41.5%) abstract conclusion sections. Of the 21 RCTs reporting a clinical trial registry, 3 (14.3%) had evidence of selective reporting bias.ConclusionsOrthopedic trauma RCTs from highly ranked journals with nonsignificant endpoints published from 2012 to 2017 frequently have spin in their abstracts. Abstracts with evidence of spin may influence a reader's perception of new drugs or procedures. In orthopedic trauma, the implications of spin may affect the treatment of patients with orthopedic trauma, so efforts to mitigate spin in RCT abstracts must be prioritized.