In the 1990s, intensivists suggested a new type of sonography: lung ultrasound, based on artefacts that receive information even from physical acoustic phenomena not directly convertible into images ...of the human body. They compared the artefacts from the lung zones with no acoustic window with various computed tomography (CT) patterns. They used and still use US as a tool to evaluate patients bedside, i.e. monitoring of lung recruitment. They included Lung ultrasound in what was termed POCUS (Point-of-Care Ultrasound). Lung ultrasound has been progressively extended to paediatrics in general. The most appealing novelty has been the diagnosis of pneumothorax. Lung ultrasound was developed as a support tool for critical patients. Extrapolation with mass diffusion, in the absence of appropriate training, has led to misunderstandings and dangerous therapeutic diagnostic drifts.
In this article, we review the biological and clinical implication of the Recruitment-Secretory Block (“R-SB”) phenomenon. The phenomenon refers to the reaction of the liver with regard to protein ...secretion in conditions of clinical stimulation. Our basic knowledge of the process is due to the experimental work in animal models. Under basal conditions, the protein synthesis is mainly carried out by periportal (zone 1) hepatocytes that are considered the “professional” synthesizing protein cells. Under stimulation, midlobular and centrolobular (zones 2 and 3) hepatocytes, are progressively recruited according to lobular gradients and contribute to the increase of synthesis and secretion. The block of secretion, operated by exogenous agents, causes intracellular retention of all secretory proteins. The Pi MZ phenotype of Alpha-1-antitrypsin deficiency (AATD) has turned out to be the key for in vivo studies of the reaction of the liver, as synthesis and block of secretion are concomitant. Indeed, the M fraction of AAT is stimulated for synthesis and regularly exported while the Z fraction is mostly retained within the cell. For that reason, the phenomenon has been designated “Recruitment-Secretory Block” (“R-SB”). The “R-SB” phenomenon explains why: (a) the MZ individuals can correct the serum deficiency; (b) the resulting immonohistochemical and electron microscopic (EM) patterns are very peculiar and specific for the diagnosis of the Z mutation in tissue sections in the absence of genotyping; (c) the term carrier is no longer applicable for the heterozygous condition as all Pi MZ individuals undergo storage and the storage predisposes to liver damage. The storage represents the true elementary lesion and consequently reflects the phenotype-genotype correlation; (d) the site and function of the extrahepatic AAT and the relationship between intra and extracellular AAT; (e) last but not least, the concept of Endoplasmic Reticulum Storage Disease (ERSD) and of a new disease, hereditary hypofibrinogenemia with hepatic storage (HHHS). In the light of the emerging phenomenon, described in vitro, namely that M and Z AAT can form heteropolymers within hepatocytes as well as in circulation, we have reviewed the whole clinical and experimental material collected during forty years, in order to evaluate to what extent the polymerization phenomenon occurs in vivo. The paper summarizes similarities and differences between AAT and Fibrinogen as well as between the related diseases, AATD and HHHS. Indeed, fibrinogen gamma chain mutations undergo an aggregation process within the RER of hepatocytes similar to AATD. In addition, this work has clarified the intriguing phenomenon underlying a new syndrome, hereditary hypofibrinogenemia and hypo-APO-B-lipoproteinemia with hepatic storage of fibrinogen and APO-B lipoproteins. It is hoped that these studies could contribute to future research and select strategies aimed to simultaneously correct the hepatocytic storage, thus preventing the liver damage and the plasma deficiency of the two proteins.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objectives
Mutations affecting the
TMEM173
gene cause STING-associated vasculopathy with onset in infancy (SAVI). No standard immunosuppressive treatment approach is able to control disease ...progression in patients with SAVI. We studied the efficacy and safety of targeting type I IFN signaling with the Janus kinase inhibitor, ruxolitinib.
Methods
We used DNA sequencing to identify mutations in
TMEM173
in patients with peripheral blood type I IFN signature
.
The JAK1/2 inhibitor ruxolitinib was administered on an off-label basis.
Results
We identified three patients with SAVI presenting with skin involvement and progressive severe interstitial lung disease. Indirect echocardiographic signs of pulmonary hypertension were present in one case. Following treatment with ruxolitinib, we observed improvements of respiratory function including increased forced vital capacity in two patients, with discontinuation of oxygen therapy and resolution of echocardiographic abnormalities in one case. Efficacy was persistent in one patient and only transitory in the other two patients. Clinical control of skin complications was obtained, and one patient discontinued steroid treatment. One patient, who presented with kidney involvement, showed resolution of hematuria. One patient experienced increased recurrence of severe viral respiratory infections. Monitoring of peripheral blood type I interferon signature during ruxolitinib treatment did not show a stable decrease.
Conclusions
We conclude that targeting type I IFN receptor signaling may represent a promising therapeutic option for a subset of patients with SAVI syndrome and severe lung involvement. However, the occurrence of viral respiratory infection might represent an important cautionary note for the application of such form of treatment.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objective
The purpose of this study was to describe lung ultrasound (LUS) findings at baseline and 48 hours after the beginning of treatment and evaluate how they correlate with outcome
Design
We ...prospectively analyzed patients from 1 month to 17 years of age with community acquired pneumonia (CAP) evaluated at a tertiary level pediatric hospital. At baseline and 48 hours after the beginning of treatment, history, clinical examination, laboratory testing, chest X‐ray, and LUS were performed.
Results
One hundred one children were enrolled in the study (13 with complicated CAP). At baseline those who developed complications presented a larger size of the subpleural pulmonary parenchymal lesions (P = .001) often associated with a complex pleural effusion (63.6%, P = .013). Those with an uncomplicated CAP presented an air, arboriform, superficial and dynamic bronchogram, as opposed to complicated CAP which had an air and liquid bronchogram, deep, fixed (P = .001). At the 48‐hour control in the noncomplicated CAP group, bronchogram was more frequently superficial and dynamic (P = .050). Pleural effusion disappeared in half cases (P = .050). In all patients, neutrophilic leucocytosis with increased C‐reactive protein was detected and decreased at control (P = .001). The linear regression analyses showed the switch from a deep to a superficial bronchogram as the only explanatory variable (r = 0.97, R2 = 0.94, P = .001, t = 10.73).
Conclusions
Our study describe early LUS features of CAP that might be able to predict the development of complicated CAP.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Purpose To evaluate the diagnostic accuracy of shear-wave elastography (SWE) in identifying different degrees of fibrosis in a cohort of consecutive children and adolescents with nonalcoholic ...steatohepatitis (NASH). Materials and Methods Consecutive pediatric patients scheduled to undergo liver biopsy were studied with an ultrasonography-based SWE system. Elastography was performed in 68 of 69 patients with biopsy-proved NASH (37 boys and 31 girls; mean age, 12.6 years ± 2.48; age range, 8-17 years). The correlations among laboratory findings, liver stiffness, and fibrosis score were analyzed, and the area under the receiver operating characteristic curve (AUC) was used to assess the presence of any fibrosis (score ≥F1) or significant fibrosis (score ≥F2). Findings from histologic examination were used as the standard of reference. Results SWE showed a very high correlation with liver fibrosis (P < .001) at univariate and multivariate analyses. The AUCs for the association of any and significant fibrosis were 0.92 (95% confidence interval CI: 0.86, 0.98) and 0.97 (95% CI: 0.95, 0.99), respectively. The intraclass correlation coefficient for absolute agreement was 0.95 (95% CI: 0.90, 0.97). Conclusion SWE is an accurate and reproducible noninvasive technique that efficiently depicts the presence of significant liver fibrosis and, less accurately, mild liver fibrosis in pediatric patients with nonalcoholic fatty liver disease. Larger clinical prospective studies are warranted to confirm SWE accuracy and establish threshold values for fibrosis grading in comparison or in combination with other noninvasive methods.
RSNA, 2016.
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