Dynamic titanium prosthesis based on 3D-printed replica for chest wall resection and reconstruction

3D-printing technologies can assist the surgical planning and prosthesis engineering for the management of extended chest wall resection. Different types of prosthesis have been utilized over time, but some concerns remain about their impact on the respiratory function. Here we present a new kind of 3D-printed titanium prosthesis designed to be either strong and flexible. The prosthesis was created on a 1:1 3D-printed anatomic replica of the chest, used to delineate surgical margins and to define the reconstructive requirements

BCR-ABL1 doubling-times and halving-times may predict CML response to tyrosine kinase inhibitors

In Chronic Myeloid Leukemia (CML), successful treatment requires accurate molecular monitoring to evaluate disease response and provide timely interventions for patients failing to achieve the desired outcomes. We wanted to determine whether measuring BCR-ABL1 mRNA doubling-times (DTs) could distinguish inconsequential rises in the oncogene’s expression from resistance to tyrosine kinase inhibitors (TKIs). Thus, we retrospectively examined BCR-ABL1 evolution in 305 chronic-phase CML patients receiving imatinib mesylate (IM) as a first line treatment. Patients were subdivided in two groups: those with a confirmed rise in BCR-ABL1 transcripts without MR3.0 loss and those failing IM. We found that the DTs of the former patients were significantly longer than those of patients developing IM resistance (57.80 vs. 41.45 days, p = 0.0114). Interestingly, the DT values of individuals failing second-generation (2G) TKIs after developing IM resistance were considerably shorter than those observed at the time of IM failure (27.20 vs. 41.45 days; p = 0.0035). We next wanted to establish if decreases in BCR-ABL1 transcripts would identify subjects likely to obtain deep molecular responses. We therefore analyzed the BCR-ABL1 halving-times (HTs) of a different cohort comprising 174 individuals receiving IM in first line and observed that, regardless of the time point selected for our analyses (6, 12, or 18 months), HTs were significantly shorter in subjects achieving superior molecular responses (p = 0.002 at 6 months; p < 0.001 at 12 months; p = 0.0099 at 18 months). Moreover, 50 patients receiving 2G TKIs as first line therapy and obtaining an MR3.0 (after 6 months; p = 0.003) or an MR4.0 (after 12 months; p = 0.019) displayed significantly shorter HTs than individuals lacking these molecular responses. Our findings suggest that BCR-ABL1 DTs and HTs are reliable tools to, respectively, identify subjects in MR3.0 that are failing their assigned TKI or to recognize patients likely to achieve deep molecular responses that should be considered for treatment discontinuation

F-061 * A COMPARATIVE STUDY AMONG MINIATURIZED ULTRASOUND PROBES FOR PULMONARY NODULES DETECTION IN AN EX VIVO LUNG PERFUSION MODEL

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Using Administrative Data to Explore the Effect of Survey Nonresponse in the UK Employment Retention and Advancement Demonstration

Background: Even a well-designed randomized control trial (RCT) study can produce ambiguous results. This paper highlights a case in which full-sample results from a large-scale RCT in the United Kingdom (UK) differ from results for a sub-sample of survey respondents. Objectives: Our objective is to ascertain the source of the discrepancy in inferences across data sources and, in doing so, to highlight important threats to the reliability of the causal conclusions derived from even the strongest research designs. Research design: The study analyzes administrative data to shed light on the source of the differences between the estimates. We explore the extent to which heterogeneous treatment impacts and survey non-response might explain these differences. We suggest checks which assess the external validity of survey measured impacts, which in turn provides an opportunity to test the effectiveness of different weighting schemes to remove bias. The Subjects included 6,787 individuals who participated in a large-scale social policy experiment. Results: Our results were not definitive but suggest non-response bias is the main source of the inconsistent findings. Conclusions. The results caution against overconfidence in drawing conclusions from RCTs and highlight the need for great care to be taken in data collection and analysis. Particularly, given the modest size of impacts expected in most RCTs, small discrepancies in data sources can alter the results. Survey data remain important as a source of information on outcomes not recorded in administrative data. However, linking survey and administrative data is strongly recommended whenever possible

MC1568 inhibits HDAC6/8 activity and influenza A virus replication in lung epithelial cells: Role of Hsp90 acetylation

Aim: Histone deacetylases (HDACs) regulate the life cycle of several viruses. We investigated the ability of different HDAC inhibitors, to interfere with influenza virus A/Puerto Rico/8/34/H1N1 (PR8 virus) replication in Madin-Darby canine kidney and NCI cells. Results: 3-(5-(3-Fluorophenyl)-3-oxoprop-1-en-1-yl)-1-methyl-1H-pyrrol-2-yl)-N-hydroxyacrylamide (MC1568) inhibited HDAC6/8 activity and PR8 virus replication, with decreased expression of viral proteins and their mRNAs. Such an effect may be related to a decrease in intranuclear content of viral polymerases and, in turn, to an early acetylation of Hsp90, a major player in their nuclear import. Later, the virus itself induced Hsp90 acetylation, suggesting a differential and time-dependent role of acetylated proteins in virus replication. Conclusion: The inhibition of HDAC6/8 activity during early steps of PR8 virus replication could lead to novel anti-influenza strategy