Optimal pressure for mimicking clinical breath holding inspiratory CT in the deceased for VPMCT

Introduction Ventilated PMCT (VPMCT) has been reported to provide better quality of pulmonary structures in PMCT in adults and children. However, there are no consensus regarding optimal inflation pressure, and the practical use of VPMCT is still limited by cost of ventilation equipment. Here, we describe a simple and cost-efficient inflation-device for VPMCT and investigate optimal inflation pressure. Aim To elucidate the effect of different ventilation pressures on total lung volume and the volume of ground glass opacities (GGO), air-filled tissue, consolidations, and bronchi in VPMCT. Materials and method A precise inflation device was assembled using standard components: a back-pressure regulator, a water manometer and silicone tubing. Each case had PMCT performed at 0, 10, 20, 30 and 40 cmH2O pressure. Volumes were measured using stereology. Results 14 cases were enrolled in the study. The total lung volume increased significantly by 3612 mL (median) from 0 to 30 cmH2O (p = 0.001). The volume of consolidations was significantly reduced by 455.86 mL (median) between 0 and 30 cmH2O (p = 0.001). A significant reduction of GGO-volume of 133 mL (median) was observed at the pressure interval 30–40 cmH2O (p = 0.031), but not at lower pressures. Conclusion The constructed inflation device allowed precise and reproducible inflation of the lungs in deceased humans. We found a maximum effect of inflation at 30 cmH2O. At further inflation pressure, only the volume of GGOs decreased , but the effect was minor. For mimicking an in vivo breath-hold scan in PMCT we recommend inflation pressure of 30 cmH2O. + Graphical abstrac

Case report: Death caused by multi-organ metastatic calcifications as a result of intramuscular injections with paraffin oil

In this forensic case report, we present autopsy findings from a young male in his thirties who had been self-injecting paraffin oil into his upper extremities 8 years prior to death. The injections induced an inflammatory response, leading to granuloma formation. This, in turn, resulted in severe hypercalcemia. The external autopsy examination revealed gross macroscopic ulcerations and enlargement of upper extremities, while calcifications of ligaments, heart, kidneys and dura mater was revealed on postmortem CT-scans. Histopathological examination showed extensive multiorgan metastatic calcifications in several tissues including the lungs, heart and kidney. Cause of death was estimated to be the extensive calcific deposits in the heart likely resulting in cardiac arrest. To our knowledge this is the first case reporting findings from an autopsy in which the cause of death was linked to cosmetic oil injections

Population pharmacokinetics and pharmacogenetics of ritonavir-boosted darunavir in the presence of raltegravir or tenofovir disoproxil fumarate/emtricitabine in HIV-infected adults and the relationship with virological response : a sub-study of the NEAT001/ANRS143 randomized trial

OBJECTIVES: NEAT001/ANRS143 demonstrated non-inferiority of once-daily darunavir/ritonavir (800/100 mg) + twice-daily raltegravir (400 mg) versus darunavir/ritonavir + tenofovir disoproxil fumarate/emtricitabine (245/200 mg once daily) in treatment-naive patients. We investigated the population pharmacokinetics of darunavir, ritonavir, tenofovir and emtricitabine and relationships with demographics, genetic polymorphisms and virological failure. METHODS: Non-linear mixed-effects models (NONMEM v. 7.3) were applied to determine pharmacokinetic parameters and assess demographic covariates and relationships with SNPs (SLCO3A1, SLCO1B1, NR1I2, NR1I3, CYP3A5*3, CYP3A4*22, ABCC2, ABCC10, ABCG2 and SCL47A1). The relationship between model-predicted darunavir AUC0-24 and C24 with time to virological failure was evaluated by Cox regression. RESULTS: Of 805 enrolled, 716, 720, 347 and 361 were included in the darunavir, ritonavir, tenofovir and emtricitabine models, respectively (11% female, 83% Caucasian). No significant effect of patient demographics or SNPs was observed for darunavir or tenofovir apparent oral clearance (CL/F); coadministration of raltegravir did not influence darunavir or ritonavir CL/F. Ritonavir CL/F decreased by 23% in NR1I2 63396C>T carriers and emtricitabine CL/F was linearly associated with creatinine clearance (P < 0.001). No significant relationship was demonstrated between darunavir AUC0-24 or C24 and time to virological failure [HR (95% CI): 2.28 (0.53-9.80), P = 0.269; and 1.82 (0.61-5.41), P = 0.279, respectively]. CONCLUSIONS: Darunavir concentrations were unaltered in the presence of raltegravir and not associated with virological failure. Polymorphisms investigated had little impact on study-drug pharmacokinetics. Darunavir/ritonavir + raltegravir may be an appropriate option for patients experiencing NRTI-associated toxicity