Quantitative CT analysis in patients with pulmonary emphysema: is lung function influenced by concomitant unspecific pulmonary fibrosis?

Purpose: Quantitative analysis of CT scans has proven to be a reproducible technique, which might help to understand the pathophysiology of chronic obstructive pulmonary disease (COPD) and combined pulmonary fibrosis and emphysema. The aim of this retrospective study was to find out if the lung function of patients with COPD with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages III or IV and pulmonary emphysema is measurably influenced by high attenuation areas as a correlate of concomitant unspecific fibrotic changes of lung parenchyma. Patients and methods: Eighty-eight patients with COPD GOLD stage III or IV underwent CT and pulmonary function tests. Quantitative CT analysis was performed to determine low attenuation volume (LAV) and high attenuation volume (HAV), which are considered to be equivalents of fibrotic (HAV) and emphysematous (LAV) changes of lung parenchyma. Both parameters were determined for the whole lung, as well as peripheral and central lung areas only. Multivariate regression analysis was used to correlate HAV with different parameters of lung function. Results: Unlike LAV, HAV did not show significant correlation with parameters of lung function. Even in patients with a relatively high HAVof more than 10%, in contrast to HAV (p=0.786) only LAV showed a significantly negative correlation with forced expiratory volume in 1 second (r=−0.309, R2=0.096, p=0.003). A severe decrease of DLCO% was associated with both larger HAV (p=0.045) and larger LAV (p=0.001). Residual volume and FVC were not influenced by LAV or HAV. Conclusion: In patients with COPD GOLD stage III-IV, emphysematous changes of lung parenchyma seem to have such a strong influence on lung function, which is a possible effect of concomitant unspecific fibrosis is overwhelmed

Impact of quantitative pulmonary emphysema score on the rate of pneumothorax and chest tube insertion in CT-guided lung biopsies

The aim of this study was to evaluate the risk of pneumothorax and need for chest tube insertion in CT-guided lung biopsies and identify predictors focusing on pulmonary emphysema determined with quantitative computed tomography. To that end, we retrospectively analysed the incidence of pneumothorax and chest tube insertion in 371 CT-guided lung biopsies with respect to the quantitative emphysema score determined with the density mask technique. Other possible impact factors considered were lesion diameter, length of biopsy pathway within the lung parenchyma, lung lobe, needle size, puncture technique, patient positioning and interventionalist’s level of experience. Quantitative emphysema scores of the lung were significantly higher in patients who developed instant pneumothorax (27%, p < 0.0001), overall pneumothorax (38%, p = 0.001) and had chest tube insertion (9%, p = 0.006) compared to those who did not when analysed with the Mann–Whitney U-test. In logistic regression analysis with inclusion of the other possible impact factors, the quantitative emphysema score remained a statistically significant predictor for all three output parameters. This was confirmed with least absolute shrinkage and selection operator (Lasso) regression analysis. In conclusion, quantitatively determined pulmonary emphysema is a positive predictor of the pneumothorax rate in CT-guided lung biopsy and likelihood of chest tube insertion

Comparison of distinctive models for calculating an interlobar emphysema heterogeneity index in patients prior to endoscopic lung volume reduction

Background: The degree of interlobar emphysema heterogeneity is thought to play an important role in the outcome of endoscopic lung volume reduction (ELVR) therapy of patients with advanced COPD. There are multiple ways one could possibly define interlobar emphysema heterogeneity, and there is no standardized definition. Purpose: The aim of this study was to derive a formula for calculating an interlobar emphysema heterogeneity index (HI) when evaluating a patient for ELVR. Furthermore, an attempt was made to identify a threshold for relevant interlobar emphysema heterogeneity with regard to ELVR. Patients and methods: We retrospectively analyzed 50 patients who had undergone technically successful ELVR with placement of one-way valves at our institution and had received lung function tests and computed tomography scans before and after treatment. Predictive accuracy of the different methods for HI calculation was assessed with receiver-operating characteristic curve analysis, assuming a minimum difference in forced expiratory volume in 1 second of 100 mL to indicate a clinically important change. Results: The HI defined as emphysema score of the targeted lobe (TL) minus emphysema score of the ipsilateral nontargeted lobe disregarding the middle lobe yielded the best predicative accuracy (AUC =0.73, P=0.008). The HI defined as emphysema score of the TL minus emphysema score of the lung without the TL showed a similarly good predictive accuracy (AUC =0.72, P=0.009). Subgroup analysis suggests that the impact of interlobar emphysema heterogeneity is of greater importance in patients with upper lobe predominant emphysema than in patients with lower lobe predominant emphysema. Conclusion: This study reveals the most appropriate ways of calculating an interlobar emphysema heterogeneity with regard to ELVR

Impact of interventionalist’s experience and gender on radiation dose and procedural time in CT-guided interventions—a retrospective analysis of 4380 cases over 10 years

Objectives: To investigate the impact of the interventionalist's experience and gender on radiation dose and procedural time in CT-guided interventions. Methods: We retrospectively analyzed 4380 CT-guided interventions performed at our institution with the same CT scanner from 2009 until 2018, 1287 (29%) by female and 3093 (71%) by male interventionalists. Radiation dose, number of CT fluoroscopy images taken per intervention, total procedural time, type of intervention, and degree of difficulty were derived from the saved dose reports and images. All 16 interventionalists included in this analysis performed their first CT-guided interventions during the study period, and interventions performed by each interventionalist were counted to assess the level of experience for each intervention in terms of the number of prior interventions performed by her or him. The Mann-Whitney U test (MWU test), multivariate regression, and linear mixed model analysis were performed. Results: Assessment of the impact of gender with the MWU test revealed that female interventionalists took a significantly smaller number of images (p < 0.0001) and achieved a lower dose-length product per intervention (p < 0.0001) while taking more time per intervention (p = 0.0001). This finding was confirmed for most types of interventions when additionally accounting for other possible impact factors in multivariate regression analysis. In linear mixed model analysis, we found that radiation dose, number of images taken per intervention, and procedural time decreased statistically significantly with interventionalist's experience. Conclusions: Radiation doses of CT-guided interventions are reduced by interventionalist's experience and, for most types of interventions, when performed by female interventionalists. Key points: • Radiation doses in CT-guided interventions are lower when performed by female interventionalists. • Procedural times of CT-guided interventions are longer when performed by female interventionalists. • Radiation doses of CT-guided interventions decrease with the interventionalist's experience

An Integrative Approach of the Fissure Completeness Score and Chartis Assessment in Endobronchial Valve Treatment for Emphysema

Purpose: Lung volume reduction using one-way endobronchial valves is a bronchoscopic treatment for patients with severe emphysema without collateral ventilation between the treatment target lobe and the ipsilateral lobe(s). CT-scan fissure analysis is often used as a surrogate to predict the absence of collateral ventilation. We aimed to evaluate the predictive value of the fissure completeness score (FCS) compared to the functional Chartis measurement of collateral ventilation and to provide cut-off values of the FCS in patient selection. Patients and Methods: Multicenter study in patients eligible for treatment with one-way valves. The FCS was calculated by quantitative CT analysis (Thirona, the Netherlands) and compared to status of interlobar collateral ventilation measured with Chartis system (PulmonX, USA). Thresholds were calculated for the predictive values of the presence of collateral ventilation. Results: An FCS >95% of the left major fissure had a positive predictive value (PPV) of 91%, with 1 in 11 fissures demonstrating collateral ventilation with Chartis measurement, whereas an FCS of ≤80% had a negative predictive value (NPV) of 100% for the presence of collateral ventilation. For the right major fissure, the NPV was 100% for an FCS ≤90%, but 69.7% for the right upper lobe fissure. Conclusion: Quantitative CT analysis is recommended in all patients evaluated for endo-bronchial valves. Patients with incomplete fissures (left major fissure: FCS 95%

MTOR regulates endocytosis and nutrient transport in proximal tubular cells

Renal proximal tubular cells constantly recycle nutrients to ensure minimal loss of vital substrates into the urine. Although most of the transport mechanisms have been discovered at the molecular level, little is known about the factors regulating these processes. Here, we show that mTORC1 and mTORC2 specifically and synergistically regulate PTC endocytosis and transport processes. Using a conditional mouse genetic approach to disable nonredundant subunits of mTORC1, mTORC2, or both, we showed that mice lacking mTORC1 or mTORC1/mTORC2 but not mTORC2 alone develop a Fanconi-like syndrome of glucosuria, phosphaturia, aminoaciduria, low molecular weight proteinuria, and albuminuria. Interestingly, proteomics and phosphoproteomics of freshly isolated kidney cortex identified either reduced expression or loss of phosphorylation at critical residues of different classes of specific transport proteins. Functionally, this resulted in reduced nutrient transport and a profound perturbation of the endocytic machinery, despite preserved absolute expression of the main scavenger receptors, MEGALIN and CUBILIN. Our findings highlight a novel mTOR–dependent regulatory network for nutrient transport in renal proximal tubular cells

Protein Kinase C Delta (PKCδ) Affects Proliferation of Insulin-Secreting Cells by Promoting Nuclear Extrusion of the Cell Cycle Inhibitor p21Cip1/WAF1

BACKGROUND:High fat diet-induced hyperglycemia and palmitate-stimulated apoptosis was prevented by specific inhibition of protein kinase C delta (PKCδ) in β-cells. To understand the role of PKCδ in more detail the impact of changes in PKCδ activity on proliferation and survival of insulin-secreting cells was analyzed under stress-free conditions. METHODOLOGY AND PRINCIPAL FINDINGS:Using genetic and pharmacological approaches, the effect of reduced and increased PKCδ activity on proliferation, apoptosis and cell cycle regulation of insulin secreting cells was examined. Proteins were analyzed by Western blotting and by confocal laser scanning microscopy. Increased expression of wild type PKCδ (PKCδWT) significantly stimulated proliferation of INS-1E cells with concomitant reduced expression and cytosolic retraction of the cell cycle inhibitor p21(Cip1/WAF1). This nuclear extrusion was mediated by PKCδ-dependent phosphorylation of p21(Cip1/WAF1) at Ser146. In kinase dead PKCδ (PKCδKN) overexpressing cells and after inhibition of endogenous PKCδ activity by rottlerin or RNA interference phosphorylation of p21(Cip1/WAF1) was reduced, which favored its nuclear accumulation and apoptotic cell death of INS-1E cells. Human and mouse islet cells express p21(Cip1/WAF1) with strong nuclear accumulation, while in islet cells of PKCδWT transgenic mice the inhibitor resides cytosolic. CONCLUSIONS AND SIGNIFICANCE:These observations disclose PKCδ as negative regulator of p21(Cip1/WAF1), which facilitates proliferation of insulin secreting cells under stress-free conditions and suggest that additional stress-induced changes push PKCδ into its known pro-apoptotic role

Selecting Patients for Lobar Lung Volume Reduction Therapy: What Quantitative Computed Tomography Parameters Matter?

PURPOSE  Evaluation of emphysema distribution with quantitative computed tomography (qCT) prior to endoscopic lung volume reduction (ELVR) is recommended. The aim of this study was to determine which of the commonly assessed qCT parameters prior to endoscopic lung volume reduction (ELVR) best predicts outcome of treatment. MATERIALS AND METHODS  50 patients who underwent technically successful ELVR at our institution were retrospectively analyzed. We performed quantitative analysis of the CT scans obtained prior to ELVR and carried out Mann-Whitney U-tests and a logistic regression analysis to identify the qCT parameters that predict successful outcome of ELVR in terms of improved forced expiratory volume in 1 second (FEV1). RESULTS  In the Mann-Whitney U-test, the interlobar emphysema heterogeneity index (p = 0.008) and the pulmonary emphysema score (p = 0.022) showed a statistically significant difference between responders and non-responders. In multiple logistic regression analysis only the interlobar emphysema heterogeneity index (p = 0.008) showed a statistically significant impact on the outcome of ELVR, while targeted lobe volume, total lung volume, targeted lobe emphysema score and total lung emphysema score did not. CONCLUSION  Of all commonly assessed quantitative CT parameters, only the heterogeneity index definitely allows prediction of ELVR outcome in patients with advanced chronic obstructive pulmonary disease (COPD). KEY POINTS   · Quantitative CT is recommended prior to ELVR.. · The relevance of the obtained parameters from quantitative CT remains controversial.. · This study confirms that only the emphysema heterogeneity index has a definite impact.. CITATION FORMAT · Theilig DC, Huebner R, Neumann K et al. Selecting Patients for Lobar Lung Volume Reduction Therapy: What Quantitative Computed Tomography Parameters Matter?. Fortschr Röntgenstr 2018; DOI: 10.1055/a-0638-0058

Combined morphological and functional liver MRI using spin-lattice relaxation in the rotating frame (T1ρ) in conjunction with Gadoxetic Acid-enhanced MRI

Abstract Noninvasive early detection of liver cirrhosis and fibrosis is essential for management and therapy. The aim was to investigated whether a combination of the functional parameter relative enhancement (RE) on Gadoxetic Acid magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI) and the fibrosis parameter T1ρ distinguishes cirrhosis and healthy liver. We analyzed patients with Gd-EOB-DTPA-enhanced MRI and T1ρ mapping. Signal intensity was measured before and after contrast; RE was calculated. T1ρ was measured with circular regions of interest (T1ρ-cROI). A quotient of RE and T1ρ-cROI was calculated: the fibrosis function quotient (FFQ). Cirrhosis was evaluated based on morphology and secondary changes. 213 datasets were included. The difference between cirrhotic and noncirrhotic liver was 51.11 ms vs. 47.56 ms for T1ρ-cROI (p < 0.001), 0.59 vs. 0.70 for RE (p < 0.001), and 89.53 vs. 70.83 for FFQ (p < 0.001). T1ρ-cROI correlated with RE, r = −0.14 (p < 0.05). RE had an AUC of 0.73. The largest AUC had the FFQ with 0.79. The best cutoff value was 48.34 ms for T1ρ-cROI, 0.70 for RE and 78.59 ms for FFQ. In conclusion T1ρ and RE can distinguish between cirrhotic and noncirrhotic liver. The FFQ, which is the combination of the two, improves diagnostic performance