Purpose: The purpose of the study was to evaluate the role of intravoxel incoherent motion (IVIM) diffusion model for the assessment of liver fibrosis and inflammation in diffuse liver disorders, also considering the presence of liver steatosis and iron deposits. Methods: Seventy-four patients were included, with liver biopsy and a 3 Tesla abdominal magnetic resonance imaging examination, with an IVIM diffusion-weighted sequence (single-shot spin-echo echo-planar sequence, with gradient reversal fat suppression; 6 b-values: 0, 50, 200, 400, 600, and 800 s/mm 2 ). Histological evaluation comprised the Ishak modified scale, for grading inflammation and fibrosis, plus steatosis and iron loading classification. The liver apparent diffusion coefficient (ADC) and IVIM parameters (D, D*, f) were calculated from the IVIM images. The relationship between IVIM parameters and histopathological scores were evaluated by ANOVA and Spearman correlation tests. A testretest experiment assessed reproducibility and repeatability in 10 healthy volunteers and 10 randomly selected patient studies. Results: ADC and f values were lower with higher fibrosis stages (p = 0.009, p = 0.006, respectively) and also with higher necro-inflammatory activity grades (p = 0.02, p = 0.017, respectively). Considered together, only fibrosis presented a significant effect on ADC and f measurements (p < 0.05), whereas inflammation had no significant effect (p > 0.05). A mild correlation was found between ADC and f with fibrosis (R S = -0.32 and R S = -0.38; p < 0.05) and inflammation (R S = -0.31 and R S = -0.32, p < 0.05; respectively). The AUROC for ADC and f measurements with the different dichotomizations between fibrosis or inflammation grades were only fair (0.670 to 0.749, p < 0.05). Neither D nor D* values were significantly different between liver fibrosis or inflammation grades. D measurements were significantly different across histologic grades of steatosis (p < 0.001) and iron overload (p < 0.001), whereas f measurements showed significant differences across histologic steatosis grades (p = 0.005).

Our findings suggest that proficiency in TBLC is achieved at approximately the 70th procedure; however they need to be validated in more series and cohorts.

Patients with chronic diffuse liver diseases have concomitant hepatic, splenic, and bone marrow iron loading. The highest hepatic iron scores and iron inside Kupffer cells were associated with the highest splenic and bone marrow deposits, suggesting systemic iron accumulation in the mononuclear phagocytic system.

Identification of targetable molecular changes is essential for selecting appropriate treatment in patients with advanced lung adenocarcinoma. Methods: In this study, a Sanger sequencing plus Fluorescence In Situ Hybridization (FISH) sequential approach was compared with a Next-Generation Sequencing (NGS)-based approach for the detection of actionable genomic mutations in an experimental cohort (EC) of 117 patients with advanced lung adenocarcinoma. Its applicability was assessed in small biopsies and cytology specimens previously tested for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutational status, comparing the molecular changes identified and the impact on clinical outcomes. Subsequently, an NGS-based approach was applied and tested in an implementation cohort (IC) in clinical practice. Using Sanger and FISH, patients were classified as EGFR-mutated (n = 22, 18.8%), ALK-mutated (n = 9, 7.7%), and unclassifiable (UC) (n = 86, 73.5%). Retesting the EC with NGS led to the identification of at least one gene variant in 56 (47.9%) patients, totaling 68 variants among all samples. Still, in the EC, combining NGS plus FISH for ALK, patients were classified as 23 (19.7%) EGFR; 20 (17.1%) KRAS; five (4.3%) B-Raf proto-oncogene (BRAF); one (0.9%) Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2); one (0.9%) STK11; one (0.9%) TP53, and nine (7.7%) ALK mutated. Only 57 (48.7%) remained genomically UC, reducing the UC rate by 24.8%. Fourteen (12.0%) patients presented synchronous alterations. Concordance between NGS and Sanger for EGFR status was very high (κ = 0.972; 99.1%). In the IC, a combined DNA and RNA NGS panel was used in 123 patients. Genomic variants were found in 79 (64.2%). In addition, eight (6.3%) EML4-ALK, four (3.1%), KIF5B-RET, four (3.1%) CD74-ROS1, one (0.8%) TPM3-NTRK translocations and three (2.4%) exon 14 skipping MET Proto-Oncogene (MET) mutations were detected, and 36% were treatable alterations. Conclusions: This study supports the use of NGS as the first-line test for genomic profiling of patients with advanced lung adenocarcinoma.

Unexpected child death investigation is a difficult area of forensic practice in view of the wide range of possible genetic, congenital, and acquired natural and nonnatural causes. Idiopathic infantile arterial calcification (IIAC) is a rare autosomic recessive disease usually diagnosed postmortem. Inactivating mutations of the ENPP1 gene were described in 80% of the cases with IIAC. We report a case of a 5-year-old girl submitted to a forensic autopsy due to sudden death and possible medical negligence/parents child abuse. Major alterations found (intimal proliferation and deposition of calcium hydroxyapatite around the internal elastic lamina and media of arteries; acute myocardial infarct, stenotic and calcified coronary artery; perivascular and interstitial myocardial fibrosis; and subendocardial fibroelastosis) were diagnostic of IIAC. We reviewed IIAC cases published in the English literature and highlight the importance of adequate autopsy evaluation in cases of sudden child death.

IntroductionAcute fibrinous and organizing pneumonia (AFOP) is a rare diffuse pulmonary disease, but it is not yet known whether it is a distinct form of interstitial pneumonia or simply a reflection of a tissue sampling issue.MethodsCross-sectional evaluation of clinical and radiological findings, treatments, and outcomes for patients with histologically confirmed AFOP at a tertiary university hospital between 2002 and 2015.ResultsThirteen patients (7 women, 53.8%) with a mean ± SD age of 53.5 ± 16.1 years were included. The main symptoms were fever (69.2%), cough (46.2%), and chest pain (30.8%). All patients presented a radiological pattern of consolidation and 5 (38.5%) had simultaneous ground-glass areas. Histology was obtained by computed tomography-guided transthoracic biopsy in 61.5% of cases and by surgical lung biopsy in the remaining cases. Several potential etiologic factors were identified. Eight patients (61.5%) had hematologic disorders and 3 had undergone an autologous hematopoietic cell transplant. Two (15.4%) had microbiologic isolates, 5 (38.4%) had drug-induced lung toxicity, and 2 (15.4%) were classified as having idiopathic AFOP. In addition to antibiotics and diuretics used to treat the underlying disease, the main treatment was corticosteroids, combined in some cases with immunosuppressants. Median survival was 78 months and 6 patients (46.2%) were still alive at the time of analysis.ConclusionOur findings for this series of patients confirm that AFOP is a nonspecific reaction to various agents with a heterogeneous clinical presentation and clinical course that seems to be influenced mainly by the severity of the underlying disorder.

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Cigarettes are well-recognized risk factors responsible for the emergence of a variety of pathologic conditions affecting both the airways and the lungs. Smoking-related lung diseases can be classified as chronic obstructive pulmonary disease (COPD) and several types of interstitial diseases, such as pulmonary Langerhans cell histiocytosis, bronchiolitis, desquamative interstitial pneumonitis, acute eosinophilic pneumonia, and interstitial fibrosing lung diseases. The evidence of combined lower lung fibrosis and predominant upper lung emphysema is renowned as a distinct clinical entity, named combined pulmonary fibrosis and emphysema. Although computerized tomography permits an adequate classification and distinction of these diseases, the clinical, imaging, and histological features often overlap and coexist in a single patient. Therefore, a combined radiologic and pathologic approach, in the appropriate clinical setting, is useful for best comprehension and distinction of these entities. Our goals are to describe the imaging features in smoking-related lung diseases and how the pathological manifestations translate on high-resolution computerized tomography.