Exposure–Response Analysis of Osimertinib in EGFR Mutation Positive Non-Small Cell Lung Cancer Patients in a Real-Life Setting

Pharmaceutical Research - Osimertinib, an irreversible inhibitor of the epidermal growth factor receptor (EGFR) is an important drug in the treatment of EGFR-mutation positive non-small cell lung...     

Effect of nerve graft porosity on the refractory period of regenerating nerve fibers

OBJECT: In the present study the authors consider the influence of the porosity of synthetic nerve grafts on peripheral nerve regeneration. METHODS: Microporous (1-13 microm) and nonporous nerve grafts made of a copolymer of trimethylene carbonate and epsilon-caprolactone were tested in an animal model. Twelve weeks after surgery, nerve and muscle morphological and electrophysiological results of regenerated nerves that had grown through the synthetic nerve grafts were compared with autografted and untreated (control) sciatic nerves. Based on the observed changes in the number and diameter of the nerve fibers, the predicted values of the electrophysiological parameters were calculated. RESULTS: The values of the morphometric parameters of the peroneal nerves and the gastrocnemius and anterior tibial muscles were similar if not equal in the rats receiving synthetic nerve grafts. The refractory periods, however, were shorter in porous compared with nonporous grafted nerves, and thus were closer to control values. CONCLUSIONS: A shorter refractory period enables the axon to follow the firing frequency of the neuron more effectively and allows a more adequate target organ stimulation. Therefore, porous are preferred over nonporous nerve grafts.     

The effects of tooth extraction on alveolar bone biomechanics in the miniature pig, Sus scrofa

Objective

This study investigated the role of occlusion in the development of biomechanical properties of alveolar bone in the miniature pig, Sus scrofa. The hypothesis tested was that the tissues supporting an occluding tooth would show greater stiffness and less strain than that of a non-occluding tooth.

Design

Maxillary teeth opposing the erupting lower first molar (M₁) were extracted on one side. Occlusion developed on the contralateral side. Serially administered fluorochrome labels tracked bone mineralisation apposition rate (MAR). A terminal experiment measured in vivo buccal alveolar bone strain on occluding and non-occluding sides during mastication. Ex vivo alveolar strains during occlusal loading were subsequently measured using a materials testing machine (MTS/Sintech). Whole specimen stiffness and principal strains were calculated.

Results

MAR tended to be higher on the extraction side during occlusion. In vivo buccal shear strains were higher in the alveolar bone of the occluding side vs. the extraction side (mean of 471 μ? vs. 281 μ?, respectively; p = 0.04); however, ex vivo shear strains showed no significant differences between sides. Stiffness differed between extraction and occlusion side specimens, significantly so in the low load range (344 vs. 668 MPa, respectively; p = 0.04).

Conclusions

Greater in vivo shear strains may indicate more forceful chews on the occluding side, whereas the similarity in ex vivo bone strain magnitude suggests a similarity in alveolar bone structure and occlusal load transmission regardless of occlusal status. The big overall change in specimen stiffness that was observed was likely attributable to differences in the periodontal ligament rather than alveolar bone.     

Low dose unenhanced helical computerized tomography for the evaluation of acute flank pain

PURPOSE: Unenhanced helical computerized tomography (CT) has proved to be an excellent diagnostic tool for evaluating acute flank pain with reported 95% to 100% sensitivity, 92% to 100% specificity, 96% to 100% positive and 91% to 100% negative predictive values. The diagnostic value of a new low dose protocol was prospectively studied and compared with the results of conventional unenhanced helical CT in a previous series with an effective dose equivalent (HE) of 3.1 to 4.3 mSv. and in current literature with an estimated HE of 4.3 to 4.7 mSv. MATERIALS AND METHODS: In 109 patients 18 to 86 years old with acute flank pain we performed low dose unenhanced helical CT in addition to abdominal ultrasound and urinalysis with new CT parameters (120 kV. 70 mA., 5 mm. collimation, pitch 2 and incremental reconstruction each 5 mm.) that led to a more than 50% decrease in radiation exposure to 1.50 mSv. in females and 0.98 mSv. in males. Ureteral calculi were confirmed or excluded by retrograde ureteropyelography in 51 cases. In the other cases the diagnosis was verified by the clinical and ultrasound course, and/or stone asservation. RESULTS: In 80 of the 109 patients the flank pain was caused by a ureteral calculus. Low dose unenhanced helical CT precisely identified 77 ureteral calculi with 1 false-positive finding. Thus, the sensitivity and specificity of low dose unenhanced helical CT were 96% and 97% with a 99% positive and 90% negative predictive value. In 15 of 29 patients with CT findings negative for stone disease different causes of pain were established by low dose unenhanced helical CT. CONCLUSIONS: Even with the significantly decreased radiation exposure of the low dose protocol unenhanced helical CT is still an excellent and rapid diagnostic tool for evaluating acute flank pain with lower radiation exposure than excretory urography (HE 1.3 to 2.3 mSv.) at our departments. Only in obese patients with a body mass index of greater than 31 kg./m.2 is conventional unenhanced helical CT with higher radiation exposure recommended to achieve adequate image quality.     

Cutting balloon for in-stent restenosis: acute and long-term results

INTRODUCTION: Conventional percutaneous coronary intervention for the treatment of in-stent restenosis (ISR) has shown a high rate of ISR (30-55%). Considering the need for both extrusion of hyperplastic intima and additional stent expansion, a cutting balloon might be more effective for the treatment of ISR. METHODS: We prospectively assessed the immediate and 8-month outcome of balloon angioplasty using the Barath Cutting Balloon in 100 consecutive patients (mean age: 60.5 +/- 10.8 years, 71% male). RESULTS: In 73 lesions (73%), a good result was reached with the cutting balloon only. In 21 lesions (21%) postdilatation and in 6 lesions (6%) predilatation with a conventional balloon was necessary. The mean inflation pressure was 8.7 +/- 2.0 (range: 6.0-18.0) atm. Before the procedure the mean minimal luminal diameter (MLD) was 0.95 +/- 0.45 mm. Quantitative coronary analysis showed a mean diameter stenosis of 65%+/- 16%. Immediately after the procedure the mean MLD was 2.42 +/- 0.54 mm with a mean diameter stenosis of 19%+/- 13%. Two patients died during the follow-up period (1 stroke, 1 nonvascular). At 8-month follow-up 26 patients (26%) reported to have anginal complaints CCS class II-IV of whom 16 (16%) needed target lesion revascularization. CONCLUSION: Treatment of ISR using the Barath Cutting Balloon can be performed safely with good immediate results and a relatively low need for repeated target lesion revascularization at 8-month follow-up.