Novel positron emission tomography/computed tomography of diffuse parenchymal lung disease combining a labeled somatostatin receptor analogue and 2-deoxy-2[¹⁸F]fluoro-D-glucose

We prospectively investigated the potential of positron emission tomography (PET) using the somatostatin receptor (SSTR) analogue ⁶⁸Ga-DOTATATE and 2-deoxy-2[¹⁸F]fluoro-D-glucose (¹⁸F-FDG) in diffuse parenchymal lung disease (DPLD). Twenty-six patients (mean age 68.9 ± 11.0 years) with DPLD were recruited for ⁶⁸Ga-DOTATATE and ¹⁸F-FDG combined PET/high-resolution computed tomography (HRCT) studies. Ten patients had idiopathic pulmonary fibrosis (IPF), 12 patients had nonspecific interstitial pneumonia (NSIP), and 4 patients had other forms of DPLD. Using PET, the pulmonary tracer uptake (maximum standardized uptake value [SUV(max)]) was calculated. The distribution of PET tracer was compared to the distribution of lung parenchymal changes on HRCT. All patients demonstrated increased pulmonary PET signal with ⁶⁸Ga-DOTATATE and ¹⁸F-FDG. The distribution of parenchymal uptake was similar, with both tracers corresponding to the distribution of HRCT changes. The mean SUV(max) was 2.2 ± 0.7 for ⁶⁸Ga-DOTATATE and 2.8 ± 1.0 (t-test, p  =  .018) for ¹⁸F-FDG. The mean ⁶⁸Ga-DOTATATE SUV(max) in IPF patients was 2.5 ± 0.9, whereas it was 2.0 ± 0.7 (p  =  .235) in NSIP patients. The correlation between ⁶⁸Ga-DOTATATE SUV(max) and gas transfer (transfer factor of the lung for carbon monoxide [TLCO]) was r  =  -.34 (p  =  .127) and r  =  -.49 (p  =  .028) between ¹⁸F-FDG SUV(max) and TLCO. We provide noninvasive in vivo evidence in humans showing that SSTRs may be detected in the lungs of patients with DPLD in a similar distribution to sites of increased uptake of ¹⁸F-FDG on PET.

Detection of gelatinolytic activity in developing basement membranes of the mouse embryo head by combining sensitive in situ zymography with immunolabeling

Genetic evidence indicates that the major gelatinases MMP-2 and MMP-9 are involved in mammalian craniofacial development. Since these matrix metalloproteinases are secreted as proenzymes that require activation, their tissue distribution does not necessarily reflect the sites of enzymatic activity. Information regarding the spatial and temporal expression of gelatinolytic activity in the head of the mammalian embryo is sparse. Sensitive in situ zymography with dye-quenched gelatin (DQ-gelatin) has been introduced recently; gelatinolytic activity results in a local increase in fluorescence. Using frontal sections of wild-type mouse embryo heads from embryonic day 14.5-15.5, we optimized and validated a simple double-labeling in situ technique for combining DQ-gelatin zymography with immunofluorescence staining. MMP inhibitors were tested to confirm the specificity of the reaction in situ, and results were compared to standard SDS-gel zymography of tissue extracts. Double-labeling was used to show the spatial relationship in situ between gelatinolytic activity and immunostaining for gelatinases MMP-2 and MMP-9, collagenase 3 (MMP-13) and MT1-MMP (MMP-14), a major activator of pro-gelatinases. Strong gelatinolytic activity, which partially overlapped with MMP proteins, was confirmed for Meckel's cartilage and developing mandibular bone. In addition, we combined in situ zymography with immunostaining for extracellular matrix proteins that are potential gelatinase substrates. Interestingly, gelatinolytic activity colocalized precisely with laminin-positive basement membranes at specific sites around growing epithelia in the developing mouse head, such as the ducts of salivary glands or the epithelial fold between tongue and lower jaw region. Thus, this sensitive method allows to associate, with high spatial resolution, gelatinolytic activity with epithelial morphogenesis in the embryo.

Predictors of Clinical Outcomes in Patients With Severe Aortic Stenosis Undergoing TAVI: A Multistate Analysis

Patients with severe aortic stenosis at increased surgical risk continue to experience compromised long-term survival despite successful transcatheter aortic valve implantation. We used time-related pathways in a multistate analysis to identify predictors of adverse long-term outcome in patients who underwent transcatheter aortic valve implantation.

Predictors of functional decline in elderly patients undergoing transcatheter aortic valve implantation (TAVI)

Aims This study aimed to assess functional course in elderly patients undergoing transcatheter aortic valve implantation (TAVI) and to find predictors of functional decline. Methods and results In this prospective cohort, functional course was assessed in patients ≥70 years using basic activities of daily living (BADL) before and 6 months after TAVI. Baseline EuroSCORE, STS score, and a frailty index (based on assessment of cognition, mobility, nutrition, instrumental and basic activities of daily living) were evaluated to predict functional decline (deterioration in BADL) using logistic regression models. Functional decline was observed in 22 (20.8%) of 106 surviving patients. EuroSCORE (OR per 10% increase 1.18, 95% CI: 0.83-1.68, P = 0.35) and STS score (OR per 5% increase 1.64, 95% CI: 0.87-3.09, P = 0.13) weakly predicted functional decline. In contrast, the frailty index strongly predicted functional decline in univariable (OR per 1 point increase 1.57, 95% CI: 1.20-2.05, P = 0.001) and bivariable analyses (OR: 1.56, 95% CI: 1.20-2.04, P = 0.001 controlled for EuroSCORE; OR: 1.53, 95% CI: 1.17-2.02, P = 0.002 controlled for STS score). Overall predictive performance was best for the frailty index [Nagelkerke's R(2) (NR(2)) 0.135] and low for the EuroSCORE (NR(2) 0.015) and STS score (NR(2) 0.034). In univariable analyses, all components of the frailty index contributed to the prediction of functional decline. Conclusion Over a 6-month period, functional status worsened only in a minority of patients surviving TAVI. The frailty index, but not established risk scores, was predictive of functional decline. Refinement of this index might help to identify patients who potentially benefit from additional geriatric interventions after TAVI.

Epidemiology and predictors of cervical spine injury in adult major trauma patients: a multicenter cohort study

Patients with cervical spine injuries are a high-risk group, with the highest reported early mortality rate in spinal trauma.