Half-dose gadobenate dimeglumine versus standard-dose gadodiamide in dynamic magnetic resonance imaging of non-cirrhotic livers: a retrospective intra-individual crossover comparison.

PURPOSE: The purpose of this study was to compare enhancement characteristics of half-dose gadobenate dimeglumine (0.05 mmol kg(-1)) with standard-dose gadodiamide (0.10 mmol kg(-1)), in the assessment of hepatic vessels and lesions, using retrospective intra-individual crossover comparison methodology. METHODS: Ethics committee approval was obtained. From 2004 to 2012, 21 patients underwent MRI examination with both standard-dose gadodiamide and half-dose gadobenate dimeglumine, using the same liver MRI protocol at 1.5 T. Eighteen patients whose scans showed no artifacts were selected. Quality of liver lesion [12 hemangiomas, 7 focal nodular hyperplasias (FNHs)] and liver vessel enhancement, and the global diagnostic quality of studies were ranked on a scale of 1-4 by two independent radiologists. Contrast-to-noise ratio (CNR) and % enhancement of liver vessels and lesions were calculated based on region of interest, signal intensity, and noise standard deviation measurements performed at 0, 20 s, 1, 3, and 5 min post-contrast injection. Qualitative and quantitative results were compared using the paired Wilcoxon signed rank and Student's t-tests, respectively. RESULTS: No qualitative differences were noted in enhancement of liver vessels, hemangiomas, and FNHs. There was no statistically significant difference between the global diagnostic qualities of scans performed with the two contrast agents. Quantitatively, liver vessels and hemangiomas did not demonstrate statistically significant differences in contrast enhancement. At 20 s, FNHs achieved higher CNR (P = 0.02) with gadodiamide. CONCLUSION: Half-dose gadobenate dimeglumine results in similar contrast enhancement compared to standard-dose gadodiamide in assessment of liver vessels, hemangiomas, and FNHs, and is a reasonable alternative to standard doses of extracellular agents in dynamic liver MRI.

Selective Targeting of Protein Kinase C (PKC)-θ Nuclear Translocation Reduces Mesenchymal Gene Signatures and Reinvigorates Dysfunctional CD8+ T Cells in Immunotherapy-Resistant and Metastatic Cancers.

Protein kinase C (PKC)-θ is a serine/threonine kinase with both cytoplasmic and nuclear functions. Nuclear chromatin-associated PKC-θ (nPKC-θ) is increasingly recognized to be pathogenic in cancer, whereas its cytoplasmic signaling is restricted to normal T-cell function. Here we show that nPKC-θ is enriched in circulating tumor cells (CTCs) in patients with triple-negative breast cancer (TNBC) brain metastases and immunotherapy-resistant metastatic melanoma and is associated with poor survival in immunotherapy-resistant disease. To target nPKC-θ, we designed a novel PKC-θ peptide inhibitor (nPKC-θi2) that selectively inhibits nPKC-θ nuclear translocation but not PKC-θ signaling in healthy T cells. Targeting nPKC-θ reduced mesenchymal cancer stem cell signatures in immunotherapy-resistant CTCs and TNBC xenografts. PKC-θ was also enriched in the nuclei of CD8+ T cells isolated from stage IV immunotherapy-resistant metastatic cancer patients. We show for the first time that nPKC-θ complexes with ZEB1, a key repressive transcription factor in epithelial-to-mesenchymal transition (EMT), in immunotherapy-resistant dysfunctional PD1+/CD8+ T cells. nPKC-θi2 inhibited the ZEB1/PKC-θ repressive complex to induce cytokine production in CD8+ T cells isolated from patients with immunotherapy-resistant disease. These data establish for the first time that nPKC-θ mediates immunotherapy resistance via its activity in CTCs and dysfunctional CD8+ T cells. Disrupting nPKC-θ but retaining its cytoplasmic function may offer a means to target metastases in combination with chemotherapy or immunotherapy.

Subarachnoid hemorrhage following chronic dural venous sinus thrombosis.

Subarachnoid hemorrhage (SAH) in older individuals is most often due to aneurysmal rupture. Other vascular lesions are known to rarely cause SAH. In this article, we report a case of chronic dural sinus thrombosis with recurrent SAH, most probably due to raised venous pressure in draining venous tributaries. No aneurysm was detected on magnetic resonance angiography or on digital subtraction angiography. The patient improved with conservative management. The case report emphasizes inclusion of magnetic resonance venography in the diagnostic workup of SAH, particularly in those cases in which aneurysm is not detected.

Role of radiotherapy in a recurrent aneurysmal bone cyst of the temporal bone: case report.

OBJECTIVE AND IMPORTANCE: A rare case of aneurysmal bone cyst (ABC) of the temporal bone is presented which, following recurrence after surgery, was successfully treated with radiotherapy. The role of radiotherapy in such cases is reviewed. CLINICAL PRESENTATION: A 30-year-old man presented with a recurrent swelling and pain in right temporal region following surgery for ABC at that site. INTERVENTION: Local radiotherapy to a dose of 31.5 Gy in 18 fractions over 3.5 weeks was delivered to the site of recurrence. The patient had a near total regression of the ABC as evident clinically and on radiological images. CONCLUSION: To the best of our knowledge, radiation for the recurrent ABC at the temporal bone has not been described in the literature. However, in view of the response evident in this patient, radiotherapy seems to be effective for recurrent cases of ABC at the temporal bone and a dose of around 30 to 36 Gy could be effectively delivered with satisfactory results.