Transit time ultrasound perivascular flow probe technology is superior to MR imaging on hepatic blood flow measurement in a porcine model

Background: The hepatic hemodynamics is an essential parameter in surgical planning as well as in various disease processes. The transit time ultrasound(TTUS) perivascular flow probe technology is widely used in clinical practice to evaluate the hepatic inflow, yet invasive. The phase-contrast-MRI(PC-MRI) is not invasive and potentially applicable in assessing the hepatic blood flow. In the present study, we compared the hepatic inflow rates using the PC-MRI and the TTUS probe, and evaluated their predictive value of post-hepatectomy adverse events. Methods: Eighteen large white pigs were anaesthetized for PC-MRI and approximately 75% hepatic resection was performed under a unified protocol. The blood flow was measured in the hepatic artery(Qha), the portal vein(Qpv), and the aorta above the celiac trunk(Qca) using PC-MRI, and was compared to the TTUS probe. The Bland-Altman method was conducted and a partial least squares regression(PLS) model was implemented. Results: The mean Qpv measured in PC-MRI was 0.55 ± 0.12 L/min, and in the TTUS probe was 0.74 ± 0.17 L/min. Qca was 1.40 ± 0.47 L/min in the PC-MRI and 2.00 ± 0.60 L/min in the TTUS probe. Qha was 0.17 ± 0.10 L/min in the PC-MRI, and 0.13 ± 0.06 L/min in the TTUS probe. The Bland-Altman method revealed that the estimated bias of Qca in the PC-MRI was 32%(95% CI:-49% to 15%); Qha 17%(95% CI:-15% to 51%); and Qpv 40%(95% CI:-62% to 18%). The TTUS probe had a higher weight in predicting adverse outcomes after 75% resection compared to the PC-MRI( β= 0.35 and 0.43 vs β = 0.22 and 0.07, for tissue changes and premature death, respectively). Conclusions: There is a tendency of the PC-MRI to underestimate the flow measured by the TTUS probes. The TTUS probe measures are more predictive of relevant post-hepatectomy outcomes.     

Toxicity evaluation and nasal mucosal tissue deposition of dexamethasone-infused mucoadhesive in situ nasal gelling systems

To demonstrate safety of a developed intranasal dexamethasone-infused in situ gelling formulation, quantification of a validated clinical biomarker indicative of cytotoxic potential using a human sinonasal explant model was first confirmed. Systematic cytotoxicity studies using the lactate dehydrogenase (LDH) detection assay revealed no elevation from baseline, in LDH levels, with tissue integrity of explanted human nasal mucosa also maintained; this was further corroborated using tissue histopathological examination. Next, with safety confirmed ex vivo, freshly excised human nasal tissue was utilised to quantify dexamethasone release from the lead sol–gel systems; this being achieved through development and validation of a HPLC-UV analytical method, which reliably quantified controlled therapeutic release and deposition into mucosal tissue. Collectively, these findings indicate promise in the safety of each excipient within the concentrations employed in the functional sol–gel system, complemented by successful and reliable drug release and deposition into human nasal mucosal tissue. These findings pave the way for application of the dexamethasone-based sol–gel system to the extended delivery of corticosteroids to nasal mucosa in the management of localised inflammatory conditions of an acute and chronic nature, such as chronic rhinosinusitis, which can be expected to benefit from controlled and extended drug delivery characteristics imparted by appropriately engineered in situ gelling systems.     

Blood pressure regulation VII. The “morning surge” in blood pressure: measurement issues and clinical significance

In keeping with this review-series theme, we question whether the morning surge in blood pressure (MSBP) is a benign response to the physiological challenges during the first 3 h after waking, or is it clinically important? Therefore, we scrutinise the circadian-related mechanisms, the measurement methods and the prognostic value of the MSBP. The MSBP is relatively small (<2 mmHg) under constant routine conditions. Nevertheless, the blood pressure response to exercise can be 8–14 mm Hg greater in the morning vs. afternoon, even when prior sleep is controlled. Systematic bias between MSBP methods can be >10 mmHg. The “sleep-trough” method provides the largest MSBP (≈25 mmHg), but the sensitivity of MSBP to a treatment/intervention depends largely on its repeatability. The repeatability standard deviation (SD) for most MSBP methods is ≈8 mm Hg. While the magnitude of this SD precludes the use of MSBP for diagnostic decisions on individual patients, sample sizes for future intervention studies may be feasible, depending on the minimal clinically important difference in MSBP. This difference is somewhat unclear given that a large MSBP has recently been reported to predict a reduced, rather than a higher, risk of cardiovascular disease, although this particular study has been criticised. The MSBP is also naturally correlated to changes in physical activity and nocturnal “dipping” status. Therefore, it is important to account for these potential confounders of the MSBP, so that more precise knowledge about its clinical significance is gained, thereby providing a sound rationale for physiological investigation and translational research.     

SUDEP classification: Discordances between forensic investigators and epileptologists

We compared sudden unexpected death in epilepsy (SUDEP) diagnosis rates between North American SUDEP Registry (NASR) epileptologists and original death investigators, to determine degree and causes of discordance. In 220 SUDEP cases with post-mortem examination, we recorded the epileptologist adjudications and medical examiner- and coroner- (ME/C) listed causes of death (CODs). COD diagnosis concordance decreased with NASR’s uncertainty in the SUDEP diagnosis: highest for Definite SUDEP (84%, n = 158), lower in Definite Plus (50%, n = 36), and lowest in Possible (0%, n = 18). Rates of psychiatric comorbidity, substance abuse, and toxicology findings for drugs of abuse were all higher in discordant cases than concordant cases. Possible SUDEP cases, an understudied group, were significantly older, and had higher rates of cardiac, drug, or toxicology findings than more certain SUDEP cases. With a potentially contributing or competing COD, ME/Cs favored non–epilepsy-related diagnoses, suggesting a bias toward listing CODs with structural or toxicological findings; SUDEP has no pathognomonic features. A history of epilepsy should always be listed on death certificates and autopsy reports. Even without an alternate COD, ME/Cs infrequently classified COD as “SUDEP.” Improved collaboration and communication between epilepsy and ME/C communities improve diagnostic accuracy, as well as bereavement and research opportunities.     

Management of advanced adenoid cystic carcinoma infiltrating the skull base: a contemporary review

Journal of Neuro-Oncology - Due to the infiltrative nature of glioblastoma (GBM) outside of the contrast-enhancing region on MRI, there is interest in exploring supratotal resections (SpTR) that...