Evaluation of spirometry-gated computed tomography to measure lung volumes in emphysema patients

INTRODUCTION: In emphysema patient being evaluated for bronchoscopic lung volume reduction (BLVR), accurate measurement of lung volumes is important. Total lung capacity (TLC) and residual volume (RV) are commonly measured by body plethysmography but can also be derived from chest computed tomography (CT). Spirometry-gated CT scanning potentially improves the agreement of CT and body plethysmography. The aim of this study was to compare lung volumes derived from spirometry-gated CT and “breath-hold-coached” CT to the reference standard: body plethysmography. METHODS: In this single-centre retrospective cohort study, emphysema patients being evaluated for BLVR underwent body plethysmography, inspiration (TLC) and expiration (RV) CT scan with spirometer guidance (“gated group”) or with breath-hold-coaching (“non-gated group”). Quantitative analysis was used to calculate lung volumes from the CT. RESULTS: 200 patients were included in the study (mean±sd age 62±8 years, forced expiratory flow in 1 s 29.2±8.7%, TLC 7.50±1.46 L, RV 4.54±1.07 L). The mean±sd CT-derived TLC was 280±340 mL lower compared to body plethysmography in the gated group (n=100), and 590±430 mL lower for the non-gated group (n=100) (both p<0.001). The mean±sd CT-derived RV was 300±470 mL higher in the gated group and 700±720 mL higher in the non-gated group (both p<0.001). Pearson correlation factors were 0.947 for TLC gated, 0.917 for TLC non-gated, 0.823 for RV gated, 0.693 for RV non-gated, 0.539 for %RV/TLC gated and 0.204 for %RV/TLC non-gated. The differences between the gated and non-gated CT results for TLC and RV were significant for all measurements (p<0.001). CONCLUSION: In severe COPD patients with emphysema, CT-derived lung volumes are strongly correlated to body plethysmography lung volumes, and especially for RV, more accurate when using spirometry gating

Effect of Chest Computed Tomography Kernel Use on Emphysema Score in Severe Chronic Obstructive Pulmonary Disease Patients Evaluated for Lung Volume Reduction

Background: Chest computed tomography (CT) emphysema quantification is a vital diagnostic tool in patient evaluation for bronchoscopic lung volume reduction (BLVR). Smooth kernels for CT image reconstruction are generally recommended for quantitative analyses. This recommendation is not always followed, which may affect quantification of emphysema extent and eventually, treatment decisions. Objective: The main goal is to demonstrate the influence of CT reconstruction kernels on emphysema quantification in patients with severe COPD, considered for BLVR. Methods: Chest CT scans were acquired with one multi-detector CT system and reconstructed using three different kernels: smooth, medium smooth, and sharp. Other parameters were kept constant. Emphysema scores (ESs), meaning the percentage of voxels below-950 Hounsfield units, were calculated and compared to the smooth reference kernel using paired t tests. Bland-Altman plots were made to assess the biases and limits of agreement between kernels. Results: Ninety-eight COPD patient CT scans were analyzed. The sharp kernel had a systematic bias of 6.2% and limits of agreement of 16.6% to-4.2% compared to the smooth kernel. The medium smooth kernel had a systematic bias of 5.7% and limits of agreement of 9.2% and 2.2% compared to the smooth kernel. The ES differed, for a single patient, up to 18% for different kernels. Conclusions: Chest CT kernel reconstruction can lead to a significant difference in emphysema severity quantification. This may cause invalid treatment selection in COPD patients evaluated for BLVR. Standardization of a smooth CT kernel setting and/or normalization to a standard kernel is strongly recommended

In vivo synergistic interaction of liposome-coencapsulated gentamicin and ceftazidime

Antimicrobial agents may interact synergistically. But to ensure synergy in vivo, the drugs should both be present at the site of infection at sufficiently high concentrations for an adequate period of time. Coencapsulation of the drugs in a drug carrier may ensure parallel tissue distributions. Since liposomes localize preferentially at sites of infection, this mode of drug delivery could, in addition, increase drug concentrations at the focus of infection. The therapeutic efficacy of gentamicin and ceftazidime coencapsulated into liposomes was examined by monitoring survival in a rat model of an acute unilateral pneumonia caused by antibiotic-susceptible and antibiotic-resistant Klebsiella pneumoniae strains. It is shown that administration of gentamicin in combination with ceftazidime in the free form either as single dose or as 5-day treatment resulted in an additive effect on rat survival in both models. In contrast, targeted delivery of liposome-coencapsulated gentamicin and ceftazidime resulted in a synergistic interaction of the antibiotics in both models. Consequently, liposome coencapsulation of gentamicin and ceftazidime allowed both a shorter course of treatment at lower cumulative doses compared with administration of the antibiotics in the free form to obtain complete survival of rats. Liposomal coencapsulation of synergistic antibiotics may open new perspectives in the treatment of severe infections

Changes in membrane sphingolipid composition modulate dynamics and adhesion of integrin nanoclusters

Sphingolipids are essential constituents of the plasma membrane (PM) and play an important role in signal transduction by modulating clustering and dynamics of membrane receptors. Changes in lipid composition are therefore likely to influence receptor organisation and function, but how this precisely occurs is difficult to address given the intricacy of the PM lipid-network. Here, we combined biochemical assays and single molecule dynamic approaches to demonstrate that the local lipid environment regulates adhesion of integrin receptors by impacting on their lateral mobility. Induction of sphingomyelinase (SMase) activity reduced sphingomyelin (SM) levels by conversion to ceramide (Cer), resulting in impaired integrin adhesion and reduced integrin mobility. Dual-colour imaging of cortical actin in combination with single molecule tracking of integrins showed that this reduced mobility results from increased coupling to the actin cytoskeleton brought about by Cer formation. As such, our data emphasizes a critical role for the PM local lipid composition in regulating the lateral mobility of integrins and their ability to dynamically increase receptor density for efficient ligand binding in the process of cell adhesion

Community standards for open cell migration data

Cell migration research has become a high-content field. However, the quantitative information encapsulated in these complex and high-dimensional datasets is not fully exploited owing to the diversity of experimental protocols and non-standardized output formats. In addition, typically the datasets are not open for reuse. Making the data open and Findable, Accessible, Interoperable, and Reusable (FAIR) will enable meta-analysis, data integration, and data mining. Standardized data formats and controlled vocabularies are essential for building a suitable infrastructure for that purpose but are not available in the cell migration domain. We here present standardization efforts by the Cell Migration Standardisation Organisation (CMSO), an open community-driven organization to facilitate the development of standards for cell migration data. This work will foster the development of improved algorithms and tools and enable secondary analysis of public datasets, ultimately unlocking new knowledge of the complex biological process of cell migration

A replication study of genetic risk loci for ischemic stroke in a Dutch population: A case-control study

We aimed to replicate reported associations of 10 SNPs at eight distinct loci with overall ischemic stroke (IS) and its subtypes in an independent cohort of Dutch IS patients. We included 1,375 IS patients enrolled in a prospective multicenter hospital-based cohort in the Netherlands, and 1,533 population-level controls of Dutch descent. We tested these SNPs for association with overall IS and its subtypes (large artery atherosclerosis, small vessel disease and cardioembolic stroke (CE), as classified by TOAST) using an additive multivariable logistic regression model, adjusting for age and sex. We obtained odds ratios (OR) with 95% confidence intervals (95% CI) for the risk allele of each SNP analyzed and exact p-values by permutation. We confirmed the association at 4q25 (PITX2) (OR 1.43; 95% CI, 1.13-1.81, p = 0.029) and 16q22 (ZFHX3) (OR 1.62; 95% CI, 1.26-2.07, p = 0.001) as risk loci for CE. Locus 16q22 was also associated with overall IS (OR 1.24; 95% CI, 1.08-1.42, p = 0.016). Other loci previously associated with IS and/or its subtypes were not confirmed. In conclusion, we validated two loci (4q25, 16q22) associated with CE. In addition, our study may suggest that the association of locus 16q22 may not be limited to CE, but also includes overall IS

The Influence of Radiograph Obliquity on Böhler's and Gissane's Angles in Calcanei

In calcaneal fractures, Böhler's and Gissane's angles are considered important parameters to guide treatment strategy and provide prognostic information during follow-up visits. Therefore, lateral radiographs have to be accurate. The aim of this study was to evaluate the effect of craniocaudal and posteroanterior angular variations (i.e., simulate lower leg malposition) from the true lateral radiograph on Böhler's and Gissane's angles. In this radioanatomical study, 15 embalmed, skeletally mature, human anatomic lower limb specimens were used. Using predefined criteria, a true lateral radiograph (i.e., 0° angular variation) was obtained. Angular variations from this true lateral radiograph were made from –30° to +30° deviation in the craniocaudal and posteroanterior direction at 5° intervals. Böhler's and Gissane angles were independently assessed by 2 experienced trauma surgeons. Böhler's angle decreased with increasing caudal angular variations (maximum –4.3° deviation at –30°). With increasing of the posterior angular variations, Böhler's angle increased (maximum 5.0° deviation at +30°) from the true lateral radiograph, but all deviations were within the measurement error. The deviation of the angle of Gissane was most pronounced in the cranial direction, with the mean angle decreasing by