This study aimed to assess the clinical impact of 68 Ga-DOTATATE and 18 F-FDG with respect to the management plan and to evaluate the prognostic value of both tracers. Methods: A total of 104 patients (55 male and 49 female; median age, 58 y; range, 20-90 y) with histologically proven neuroendocrine tumors (NETs) underwent both 68 Ga-DOTATATE and 18 F-FDG PET/CT. . Results: The 68 Ga-DOTATATE and 18 F-FDG PET/CT findings were discordant in 65 patients (62.5%) and concordant in 39 patients (37.5%). The results changed the therapeutic plan in 84 patients (80.8%). In 22 patients (21.1%), decision making was based on the 18 F-FDG findings; in 32 (30.8%), on the findings with both radiotracers; and in 50 (48.1%), on the 68 Ga-DOTATATE findings. The most frequent management decision based on 18 F-FDG was initiation of chemotherapy (10 patients, 47.6%). The most common treatment decision due to 68 Ga-DOTATATE was initiation of peptide receptor radionuclide therapy (14 patients, 27.4%). In 11 (39.2%) of 28 patients with poorly differentiated NETs, the management decision was based on only the 18 F-FDG results. For 68 Ga-DOTATATE, SUV max was higher for G1 tumors and lower for G3 tumors (P 5 0.012). However, no significant differences in 18 F-FDGderived SUVs were observed between different grades (P 5 0.38). The Mann-Whitney test showed significant differences in 68 Ga-DOTATATE SUV max between tumors with a Ki-67 of less than 5% and tumors with a Ki-67 of more than 5% (P 5 0.004), without significance differences in 18 F-FDG SUV max . Log-rank analysis showed statistically significant differences in survival for patients with bone metastasis versus soft-tissue or no metastasis for both 18 F-FDG (P 5 0.037) and 68 Ga-DOTATATE (P 5 0.047). Overall survival declined rapidly with increasing grade (P 5 0.001), at an estimated 91 mo for G1, 59 mo for G2, and 48 mo for G3. Conclusion: 18 F-FDG PET/CT had no clinical impact on G1 NETs and a moderate impact on G2 NETs. However, in poorly differentiated NETs, 18 F-FDG PET/CT plays a significant clinical role in combination with 68 Ga-DOTATATE. 68 Ga DOTATATE SUV max relates to grade and Ki-67 and can be used prognostically.

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Background: Due to the high post-stroke frequency of dysphagia, dysarthria, and aphasia, we developed comprehensive neuroanatomical, clinical, and demographic models to predict their presence after acute ischemic stroke. Methods: The sample included 160 randomly selected first-ever stroke patients with confirmed infarction on magnetic resonance imaging from 1 tertiary stroke center. We documented acute lesions within 12 neuroanatomical regions and their associated volumes. Further, we identified concomitant chronic brain disease, including atrophy, white matter hyperintensities, and covert strokes. We developed predictive models using logistic regression with odds ratios (OR) and their 95% confidence intervals (95% CI) including demographic, clinical, and acute and chronic neuroanatomical factors. Results: Predictors of dysphagia included medullary (OR 6.2, 95% CI 1.5–25.8), insular (OR 4.8, 95% CI 2.0–11.8), and pontine (OR 3.6, 95% CI 1.2–10.1) lesions, followed by brain atrophy (OR 3.0, 95% CI 1.04–8.6), internal capsular lesions (OR 2.9, 95% CI 1.2–6.6), and increasing age (OR 1.4, 95% CI 1.1–1.8). Predictors of dysarthria included pontine (OR 7.8, 95% CI 2.7–22.9), insular (OR 4.5, 95% CI 1.8–11.4), and internal capsular (OR 3.6, 95% CI 1.6–7.9) lesions. Predictors of aphasia included left hemisphere insular (OR 34.4, 95% CI 4.2–283.4), thalamic (OR 6.2, 95% CI 1.6–24.4), and cortical middle cerebral artery (OR 4.7, 95% CI 1.5–14.2) lesions. Conclusion: Predicting outcomes following acute stroke is important for treatment decisions. Determining the risk of major post-stroke impairments requires consideration of factors beyond lesion localization. Accordingly, we demonstrated interactions between localized and global brain function for dysphagia and elucidated common lesion locations across 3 debilitating impairments.

Primary cilia are essential cellular organelles that are anchored at the cell surface membrane to sense and transduce signaling. Intraflagellar transport (IFT) proteins are indispensable for cilia formation and function. Although major advances in understanding the roles of these proteins in bone development have been made, the mechanisms by which IFT proteins regulate bone repair have not been identified. We investigated the role of the IFT80 protein in chondrocytes during fracture healing by creating femoral fractures in mice with conditional deletion of IFT80 in chondrocytes utilizing tamoxifen inducible Col2α1‐CreER mice. Col2α1creIFT80f/f mice had smaller fracture calluses than IFT80f/f (control) mice. The max‐width and max‐callus area were 31% and 48% smaller than those of the control mice, respectively. Col2α1creIFT80f/f mice formed low‐density/porous woven bony tissue with significantly lower ratio of bone volume, Trabecular (Tb) number and Tb thickness, and greater Tb spacing compared to control mice. IFT80 deletion significantly downregulated the expression of angiogenesis markers‐VEGF, PDGF and angiopoietin and inhibited fracture callus vascularization. Mechanistically, loss of IFT80 in chondrocytes resulted in a decrease in cilia formation and chondrocyte proliferation rate in fracture callus compared to the control mice. Meanwhile, IFT80 deletion downregulated the TGF‐β signaling pathway by inhibiting the expression of TGF‐βI, TGF‐βR, and phosphorylation of Smad2/3 in the fracture callus. In primary chondrocyte cultures in vitro, IFT80 deletion dramatically reduced chondrocyte proliferation, cilia assembly, and chondrogenic gene expression and differentiation. Collectively, our findings demonstrate that IFT80 and primary cilia play an essential role in fracture healing, likely through controlling chondrocyte proliferation and differentiation, and the TGF‐β signaling pathway. © 2019 American Society for Bone and Mineral Research.