Target sign in COVID-19, radiological interpretation and diagnostic contribution of digital thoracic tomosynthesis.

INTRODUCTION: Our objectives are: To describe the radiological semiology, clinical-analytical features and prognosis related to the target sign (TS) in COVID-19. To determine whether digital thoracic tomosynthesis (DTT) improves the diagnostic ability of radiography. MATERIAL AND METHODS: Retrospective, descriptive, single-centre, case series study, accepted by our ethical committee. Radiological, clinical, analytical and follow-up characteristics of patients with COVID-19 and TS on radiography and DTT between November 2020 and January 2021 were analysed. RESULTS: Eleven TS were collected in 7 patients, median age 35 years, 57% male. All TS presented with a central nodule and a peripheral ring, and in at least 82%, the lung in between was of normal density. All TS were located in peripheral, basal regions and 91% in posterior regions. TS were multiple in 43%. Contiguous TS shared the peripheral ring. Other findings related to pneumonia were associated in 86% of patients. DTT detected 82% more TS than radiography. Only one patient underwent a CT angiography of the pulmonary arteries, positive for acute pulmonary thromboembolism. Seventy-one per cent presented with pleuritic pain. No distinctive laboratory findings or prognostic worsening were detected. CONCLUSIONS: TS in COVID-19 predominates in peripheral and declining regions and can be multiple. Pulmonary thromboembolism was detected in one case. It occurs in young people, frequently with pleuritic pain and does not worsen the prognosis. DTT detects more than 80 % of TS than radiography.

Heparin versus aspirin thromboprophylaxis adds independent value to IMPEDE-VTE score for venous thrombosis prediction in multiple myeloma.

Multiple myeloma (MM) is associated to an increased incidence of venous thromboembolism (VTE). IMPEDE-VTE score constitutes a valuable risk assessment tool for VTE prediction in first-line MM patients. Nevertheless, refinement of the primary thromboprophylaxis category of this score (which pools aspirin and heparin) seems desirable. To investigate the role of the type of thromboprophylaxis, within IMPEDE-VTE score, for VTE prediction in MM patients. Retrospective analysis of a single-center cohort of 438 MM patients receiving first-line antimyeloma treatment (1991-2020). IMPEDE-VTE score was calculated. Primary thromboprophylaxis was additionally stratified into aspirin- and heparin-based regimen subgroups. VTE risk was analyzed by Cox regression. Median follow-up during first-line antimyeloma treatment was 6.0 months (IQR 4.1-9.0 months). Twenty-three patients developed VTE (5.3%, 95%CI 3.4-7.8%). IMPEDE-VTE score showed a notable predictive value (area under the ROC curve: 0.70, 95%CI 0.60-0.80). Cox analysis confirmed that 1-point increase in the score resulted in a 1.3-fold increase in VTE risk (HR 1.30, 95%CI 1.13-1.53, p < 0.001). In the multivariable analysis, the type of primary thromboprophylaxis (heparin versus aspirin) was an independent predictive factor (HR 0.15, 95% CI 0.05-0.47, p = 0.001). The combined model showed a higher goodness-of-fit (Akaike Information Criterion [AIC]: 99) than IMPEDE-VTE separately (AIC:235). Our analysis contributes to the external validation of IMPEDE-VTE score for the prediction of VTE in MM. But more interestingly, our results demonstrate that among those patients receiving thromboprophylaxis, the type of regimen (heparin versus aspirin) adds independent predictive value and should be explored for a more accurate risk assessment.

Safety and antitumor effect of oncolytic and helper-dependent adenoviruses expressing interleukin-12 variants in a hamster pancreatic cancer model.

Gene transfer of potent immunostimulatory cytokines such as interleukin-12 (IL-12) is a potential treatment for advanced cancer. Different vectors and IL-12 modifications have been developed to avoid side effects associated with high serum levels of the cytokine, while preserving its antitumor properties. Here we have evaluated two alternative strategies using the Syrian hamster as a model for pancreatic cancer metastatic to the liver. Local administration of an oncolytic adenovirus (OAV) expressing a single-chain version of IL-12 caused transient, very intense elevations of IL-12 in serum, resulting in severe toxicity at sub-therapeutic doses. Anchoring IL-12 to the membrane of infected cells by fusion with the transmembrane domain of CD4 reduced systemic exposure to IL-12 and increased the tolerance to the OAV. However, only a modest increase in the therapeutic range was achieved because antitumor potency was also reduced. In contrast, systemic administration of a helper-dependent adenoviral vector (HDAd) equipped with a Mifepristone-inducible expression system allowed sustained and controlled IL-12 production from the liver. This treatment was well tolerated and inhibited the progression of hepatic metastases. We conclude that HDAds are safer than OAVs for the delivery of IL-12, and are promising vectors for immunogene therapy approaches against pancreatic cancer.