Objectives
To investigate the contribution of whole-body post-mortem computed tomography (PMCT) in sudden unexpected death in infants and children.
Methods
Forty-seven cases of sudden unexpected ...death in children investigated with radiographic skeletal survey, whole-body PMCT and autopsy were enrolled. For imaging interpretation, non-specific post-mortem modifications and abnormal findings related to the presumed cause of death were considered separately. All findings were correlated with autopsy findings.
Results
There were 31 boys and 16 girls. Of these, 44 children (93.6 %) were younger than 2 years. The cause of death was found at autopsy in 18 cases (38.3 %), with 4 confirmed as child abuse, 12 as infectious diseases, 1 as metabolic disease and 1 as bowel volvulus. PMCT results were in accordance with autopsy in all but three of these 18 cases. Death remains unexplained in 29 cases (61.7 %) and was correlated with no abnormal findings on PMCT in 27 cases. Major discrepancies between PMCT and autopsy findings concerned pulmonary analysis.
Conclusions
Whole-body PMCT may detect relevant findings that can help to explain sudden unexpected death and is essential for detecting non-accidental injuries. We found broad concordance between autopsy and PMCT, except in a few cases of pneumonia. It is a non-invasive technique acceptable to relatives.
Key Points
• Whole-body post-mortem computed tomography (PMCT) is an effective non-invasive method.
• Whole-body PMCT is essential for detecting child abuse in unexpected death.
• There is concordance on cause of death between PMCT and autopsy.
• Whole-body PMCT could improve autopsy through dissection and sampling guidance.
• PMCT shows findings that may be relevant when parents reject autopsy.
Carriers of germline telomerase‐related gene (TRG) mutations can show poor prognosis, with an increase in common hematological complications after lung transplantation (LT) for pulmonary fibrosis. ...The aim of this study was to describe the outcomes after LT in recipients carrying a germline TRG mutation and to identify the predictors of survival. In a multicenter cohort of LT patients, we retrospectively reviewed those carrying pathogenic TRG variations (n = 38; TERT, n = 23, TERC, n = 9, RTEL1, n = 6) between 2009 and 2018. The median age at LT was 54 years (interquartile range IQR 46–59); 68% were male and 71% had idiopathic pulmonary fibrosis. During the diagnosis of pulmonary fibrosis, 28 (74%) had a hematological disease, including eight with myelodysplasia. After a median follow‐up of 26 months (IQR 15–46), 38 patients received LT. The overall post‐LT median survival was 3.75 years (IQR 1.8‐NA). The risk of death after LT was increased for patients with myelodysplasia (HR 4.1 95% CI 1.5–11.5) or short telomere (HR 2.2 1.0–5.0) before LT. After LT, all patients had anemia, 66% had thrombocytopenia, and 39% had neutropenia. Chronic lung allograft dysfunction frequency was 29% at 4 years. The present findings support the use of LT in TRG mutation carriers without myelodysplasia. Hematological evaluation should be systematically performed before LT.
Among patients with telomerase‐related gene mutations who undergo lung transplantation for idiopathic pulmonary fibrosis, pre‐transplant myelodysolasia is associated with reduced post‐transplant survival.
Pim kinases (proviral integration site for Moloney murine leukemia virus kinases) are overexpressed in various types of hematological malignancies and solid carcinomas, and promote cell proliferation ...and survival. Thus, Pim kinases are validated as targets for antitumor therapy. In this context, our combined efforts in natural product-inspired library generation and screening furnished very promising dibenzo
,
furan derivatives derived from cercosporamide. Among them, lead compound
was highlighted as a potent Pim-1/2 kinases inhibitor with an additional nanomolar IC
value against CLK1 (cdc2-like kinases 1) and displayed a low micromolar anticancer potency towards the MV4-11 (AML) cell line, expressing high endogenous levels of Pim-1/2 kinases. The design, synthesis, structure-activity relationship, and docking studies are reported herein and supported by enzyme, cellular assays, and
larvae testing for acute toxicity.
Therapeutic antibodies (Abs) are emerging as major drugs to treat respiratory diseases, and inhalation may provide substantial benefits for their delivery. Understanding the behavior of Abs after ...pulmonary deposition is critical for their development. We investigated the pharmacokinetics of a nebulized Ab by continuous sampling in lung parenchyma using microdialysis in non-human primates. We defined the optimal conditions for microdialysis of Ab and demonstrated that lung microdialysis of Ab is feasible over a period of several days. The concentration-profile indicated a two-phase non-linear elimination and/or distribution of inhaled mAbX. Lung exposition was higher than the systemic one over a period of 33 hours and above MabX affinity for its target. The microdialysis results were supported by an excellent relationship with dosages from lung extracts.
Abstract
In this controlled before–after study, wound swabs were only processed for culture, identification, and susceptibility testing if a quality metric, determined by the Q score, was met. ...Rejection of low-quality wound swabs resulted in a modest decrease in reflexive antibiotic initiation while reducing laboratory workload and generating few clinician requests.
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