An Ex Vivo Human Kidney Perfusion Model Confirms Larger Microwave Ablation Dimensions After Transarterial Embolization.

PURPOSE: To utilize a novel ex vivo perfused human renal model and quantify microwave ablation (MWA) size differences in renal tissue when combining MWA with transarterial embolization (TAE). MATERIALS AND METHODS: Human kidneys (n = 5) declined for transplantation were obtained and connected to a fluoroscopic-compatible ex vivo perfusion system. Two ablations-1 standard MWA, 1 TAE-MWA-were performed in each kidney for 2 minutes at 100 Watts using a MWA system (Solero Angiodynamics). MWA alone was performed in the upper pole. In the lower pole, MWA was performed after TAE with M0 LUMI microspheres (Boston Scientific) to achieve angiographic stasis. Ablation zones of coagulative necrosis were sectioned along the long axis and segmented for maximal short axis diameter (SAD) and long axis diameter (LAD) measurements. RESULTS: A total of 10 ablations (5 MWA, 5 TAE-MWA) were performed in five human kidneys. TAE-MWA resulted in significantly increased SAD, LAD, volume, and sphericity compared to standard MWA + SD with mean measurements as follows (5 standard MWA + SD vs 5 TAE-MWA, two-tailed t-test): SAD, 1.8 ± 0.1 cm vs 2.5 ± 0.1 cm (p < 0.001); LAD, 2.9 ± 0.3 cm vs 3.2 ± 0.1 cm (p = 0.039); volume, 5.0 ± 0.5 mL vs 11.0 ± 0.7 mL (p < 0.001); sphericity, 0.4 ± 0.2 vs 0.6 ± 0.1 (p = 0.049). Histology demonstrated no differences in TAE-MWA other than concentrated microspheres. CONCLUSION: This study utilized a novel ex vivo human kidney perfusion model to confirm combined MWA-TAE significantly increases ablation size and spherical shape.

Concentration of voxelotor in sickle cell disease can be estimated using electrophoresis and high-performance liquid chromatography.

OBJECTIVES: Voxelotor can increase hemoglobin levels in patients living with sickle cell disease (SCD). A clinician who is monitoring voxelotor response may want to know whole-blood voxelotor concentration, but this cannot be measured in most clinical settings. However, voxelotor has been demonstrated to cause "peak splitting" in common methods of hemoglobin measurement such as capillary zone electrophoresis (CZE) and high-performance liquid chromatography (HPLC). We hypothesized that we could use the size of the peak split to estimate the whole-blood concentration. METHODS: Blood from people with SCD was dosed with known concentrations of voxelotor, and multiparameter regression was used to derive the relationship of voxelotor concentration to the degree of peak splitting observed. To validate these equations, 21 patients started on voxelotor at 1500 mg/d had blood samples drawn at days 0, 14, 30, and 60. Samples were sent out for gold standard voxelotor concentration testing. The derived equations were then used to calculate voxelotor concentration. RESULTS: Calculated concentrations correlated strongly with measured concentrations for both CZE (R2 = 0.83, P < .001) and HPLC (R2 = 0.76, P < .001). Voxelotor concentration also had a significant effect on increases in hemoglobin (R2 = 0.40, P < .001). CONCLUSIONS: Thus, peak splitting CZE and HPLC can be used to estimate voxelotor concentration.

Evaluation of the Catheter Clamp over Hydrophilic Guide Wire Central Venous Catheter Exchange Technique for Air Embolism Prophylaxis in an In Vitro Model.

PURPOSE: To develop a reproducible in vitro model simulating central venous catheter (CVC) exchange with high potential for air embolization and test the hypothesis that a closed catheter clamp over hydrophilic guide wire exchange technique will significantly reduce the volume of air introduced during CVC exchange. MATERIALS AND METHODS: The model consisted of a 16-F valved sheath, 240-mL container, and pressure transducer submerged in water in a 1,200-mL suction canister system. Continuous wall suction was applied to the canister to maintain negative pressure at -7 mm Hg or -11 mm Hg. Each trial consisted of 0.035-inch hydrophilic guide wire introduction, over-the-wire catheter exchange, and wire removal following clinical protocol. A total of 256 trials were performed, 128 trials at each pressure with the catheter clamp open (n = 64) or closed (n = 64) around the hydrophilic guide wire. RESULTS: There was a statistically significant lower volume of air introduced with closed clamp over-the-wire exchanges than with open clamp exchanges at both pressures (2-tailed t-test, P < .001). At -7 mm Hg, a mean of 48.0 mL (SD ± 9.3) of air was introduced with open clamp and 20.6 mL (SD ± 4.7) of air was introduced with closed clamp. At -11 mm Hg, 97.8 mL (SD ± 11.9) of air was introduced with open clamp and 37.8 mL (SD ± 6.3) of air was introduced with closed clamp. CONCLUSIONS: This study demonstrated the use of a reproducible in vitro model mimicking conditions causing air embolism during CVC exchange. Results showed that CVC exchange using closed catheter clamp over hydrophilic guide wire exchange technique significantly reduced the volume of air introduced per exchange.

GBT021601 improves red blood cell health and the pathophysiology of sickle cell disease in a murine model.

The pathophysiologic mechanism of sickle cell disease (SCD) involves polymerization of deoxygenated haemoglobin S (HbS), leading to red blood cell (RBC) sickling, decreased RBC deformability, microvascular obstruction, haemolysis, anaemia and downstream clinical complications. Pharmacological increase in the concentration of oxygenated HbS in RBCs has been shown to be a novel approach to inhibit HbS polymerization and reduce RBC sickling and haemolysis. We report that GBT021601, a small molecule that increases HbS-oxygen affinity, inhibits HbS polymerization and prevents RBC sickling in blood from patients with SCD. Moreover, in a murine model of SCD (SS mice), GBT021601 reduces RBC sickling, improves RBC deformability, prolongs RBC half-life and restores haemoglobin levels to the normal range, while improving oxygen delivery and increasing tolerance to severe hypoxia. Notably, oral dosing of GBT021601 in animals results in higher levels of Hb occupancy than voxelotor and suggests the feasibility of once-daily dosing in humans. In summary, GBT021601 improves RBC health and normalizes haemoglobin in SS mice, suggesting that it may be useful for the treatment of SCD. These data are being used as a foundation for clinical research and development of GBT021601.

The effect of non-invasive vagus nerve stimulation on memory recall in reading: A pilot study.

Expert reading acquisition is marked by fluent, effortless decoding, and adequate comprehension skills and is required for modern daily life. In spite of its importance, many individuals struggle with reading comprehension even when decoding skills are adequate. Unfortunately, effective reading comprehension interventions are limited, especially for adults. A growing body of research suggests that non-invasive transcutaneous stimulation of the auricular vagus nerve (taVNS) may drive neural plasticity for low-level reading skills such as speech sound perception and letter-sound learning, but it is unknown whether taVNS can improve higher level skills as well. Thus, the current pilot study was designed to evaluate the effect of taVNS paired with passage reading on reading comprehension performance. Twenty-four typically developing young adults were recruited and screened for baseline reading and working memory skills. Participants received either sham or active taVNS while reading short passages out loud. Immediately following each passage, participants answered a series of test questions that required either direct recall of passage details or more complete comprehension of the passage content. While taVNS did not improve the mechanics of reading (e.g., reading rate or accuracy), there was a significant effect of active taVNS on test performance. This effect was driven by significant improvement on accuracy for memory questions while there was no effect of taVNS on comprehension question accuracy. These findings suggest that taVNS may be beneficial for enhancing memory, but its efficacy may be limited in higher cognitive domains.

Creation of an Ex Vivo Renal Perfusion Model to Investigate Microwave Ablation.

This study hypothesized that an ex vivo renal perfusion model can create smaller microwave ablation (MWA) measurements during perfused states compared with nonperfused states across multiple device settings. Nine bovine kidneys, a fluoroscopic compatible perfusion model, and a commercially-available clinical MWA system were used to perform 72 ablations (36 perfused and 36 nonperfused) at 9 different device settings. Comparing perfused and nonperfused ablations at each device setting, significant differences in volume existed for 6 of 9 settings (P < .05). Collapsed across time settings, the ablation volumes by power were the following (perfused and nonperfused, P value): 60 W, 2.3 cm3 ± 1.0 and 7.2 cm3 ± 2.7, P < .001; 100 W, 5.4 cm3 ± 2.1 and 11.5 cm3 ± 5.6, P < .01; and 140 W, 11.2 cm3 ± 3.7 and 18.7 cm3 ± 6.3, P < .01. Applied power correlated with ablation volume: perfused, 0.021 cm3/W and R = 0.462, P = .004, and nonperfused, 0.029 cm3/W and R = 0.565, P < .001. These results support that an ex vivo perfused organ system can evaluate MWA systems and demonstrate heat sink perfusion effects of decreased ablation size.