Microdosimetric characterization of a clinical proton therapy beam: comparison between simulated lineal energy distributions in spherical water targets and experimental measurements with a silicon detector

Objective Treatment planning based on computer simulations were proposed to account for the increase in the relative biological effectiveness (RBE) of proton radiotherapy beams near to the edges of the irradiated volume. Since silicon detectors could be used to validate the results of these simulations, it is important to explore the limitations of this comparison. Approach Microdosimetric measurements with a MicroPlus Bridge V2 silicon detector (thickness = 10 µm) were performed along the Bragg peak of a clinical proton beam. The lineal energy distributions, the dose mean values, and the RBE calculated with a biological weighting function were compared with simulations with PHITS (microdosimetric target = 1 µm water sphere), and published clonogenic survival in vitro RBE data for the V79 cell line. The effect of the silicon-to-water conversion was also investigated by comparing three different methodologies (conversion based on a single value, novel bin-to-bin conversions based on SRIM and PSTAR). Main results Mainly due to differences in the microdosimetric targets, the experimental dose-mean lineal energy and RBE values at the distal edge were respectively up to 53% and 28% lower than the simulated ones. Furthermore, the methodology chosen for the silicon-to-water conversion was proven to affect the dose mean lineal energy and the RBE10 up to 32% and 11% respectively. The best methodology to compensate for this underestimation was the bin-to-bin silicon-to-water conversion based on PSTAR. Significance This work represents the first comparison between PHITS-simulated lineal energy distributions in water targets and corresponding experimental spectra measured with silicon detectors. Furthermore, the effect of the silicon-to-water conversion on the RBE was explored for the first time. The proposed methodology based on the PSTAR bin-to-bin conversion appears to provide superior results with respect to commonly used single scaling factors and is recommended for future studies.

“The Feasibility of Targeted Muscle Reinnervation for the Management of Morton’s Neuroma”

Background Despite multiple surgical modalities available for the management of Morton’s neuroma, complications remain common. Targeted muscle reinnervation (TMR) has yet to be explored as an option for the prevention of recurrence of Morton’s neuroma. The purpose of the present investigation was to determine the consistency of the relevant foot neurovascular and muscle anatomy and to demonstrate the feasibility of TMR as an option for Morton’s neuroma. Methods The anatomy of 5 fresh-tissue donor cadaver feet was studied, including the course and location of the medial and lateral plantar nerves (MPNs and LPNs), motor branches to abductor hallucis (AH) and flexor digitorum brevis (FDB), as well as the course of sensory plantar digital nerves. Measurements for the locations of the muscular and sensory branches were taken relative to landmarks including the navicular tuberosity (NT), AH, FDB, and the third metatarsophalangeal joint (third MTPJ). Results The mean number of nerve branches to FDB identified was 2. These branch points occurred at an average of 8.6 cm down the MPN or LPN, 9.0 cm from the third MTPJ, 3.0 cm distal to AH distal edge, and 4.8 cm from the NT. The mean number of nerves to AH was 2.2. These branch points occurred at an average of 6.3 cm down the MPN, 11.9 cm from the third MTPJ, 0.8 cm from the AH distal edge, and 3.8 cm from the NT. Conclusions Recurrent interdigital neuroma, painful scar, and neuropathic pain are common complications of operative management for Morton’s neuroma. Targeted muscle reinnervation is a technique that has demonstrated efficacy for the prevention and treatment of neuroma, neuropathic pain, and phantom limb pain in amputees. Herein, we have described the neuromuscular anatomy for the application of TMR for the management of Morton’s neuroma. Target muscles, including the AH and FDB, have consistent innervation patterns in the foot, and consequently, TMR represents a viable option to consider for the management of recalcitrant Morton’s neuroma. Levels of Evidence: V

Regenerative Polarity of the Fin Ray in Zebrafish Caudal Fin and Related Tissue Formation on the Cut Surface

Zebrafish caudal fin rays are used as a model system for regeneration because of their high regenerative ability, but studies on the regeneration polarity of the fin ray are limited. To investigate this regeneration polarity, we made a hole to excise part of the fin ray and analyzed the regeneration process. We confirmed that the fin rays always regenerated from the proximal margin toward the distal margin, as previously reported; however, regeneration-related genes were expressed at both the proximal and distal edges of the hole in the early stage of regeneration, suggesting that the regenerative response also occurs at the distal edge. One difference between the proximal and distal margins is a sheet-like tissue that is formed on the apical side of the regenerated tissue at the proximal margin. This sheet-like tissue was not observed at the distal edge. To investigate whether the distal margin was also capable of forming this sheet-like tissue and subsequent regeneration, we kept the distal margin separated from the proximal margin by manipulation. Consequently, the sheet-like tissue was formed at the distal margin and regeneration of the fin ray was also induced. The regenerated fin rays from the distal margin protruded laterally from the caudal fin and then bent distally, and their ends showed the same characteristics as those of the normal fin rays. These results suggest that fin rays have an ability to regenerate in both directions; however, under normal conditions, regeneration is restricted to the proximal margin because the sheet-like tissue is preferentially formed on the apical side of the regenerating tissue from the proximal margin.

Sinus Augmentation—Expect the Unexpected: Diagnostic Anatomical Study

“Big-nose variant” is an anatomical phenomenon defined as the pneumatization of inferior third of the nasal cavity within the alveolar ridge while simultaneously displacing the maxillary sinus laterally. The purpose of the present study was to assess the prevalence of the big-nose variant phenomenon and suggest a morphology classification system. Diagnostic anatomical evaluation was performed in a tertiary medical center on 321 randomly selected maxillary cone beam computerized tomography scans of patients who presented at an oral and maxillofacial department. Two anatomical categories were defined for anatomical identification: classes for horizontal mesiodistal distribution, and divisions for vertical distribution. Class 2, defined as location of the nasal/sinus border between the distal edge of the canine up to the distal edge of second premolar, was found to be the most prevalent (64.6%). Class 3, defined as location of the nasal/sinus border distal to mesial edge of the first molar, was found in 17.9% of cases. Regarding the divisions category, in 96% and 58.2% of teeth examined, nasal cavity alone was found to be superior to the canine and first premolar, respectively, defined as Division A. In 46.9% and 85.6% of teeth examined, maxillary sinus alone was located above the second premolar and first molar, respectively, defined as Division C. Identifying Class 3 on the paraxial reconstruction is the first step in identifying big-nose variant, with further assurance gained from each determining division. The use of the classes and divisions may enable better maxillary treatment planning, alert surgeons for the unexpected, and avoid complications.

Penetration of Dissected Membrane for False Lumen Embolization in a Case of Chronic Aortic Dissection

Background: Patent false lumens carry a high risk of aortic events including rupture. False lumen embolization is a useful method to promote thrombosis of false lumen. In the case presented here, direct penetration of the dissected membrane was employed to obtain access to the false lumen, enabling embolization. Case report: The case was a 64-year-old female who developed a Stanford type A acute aortic dissection. Replacement of ascending aorta and aortic arch with frozen elephant trunk technique was performed. After the operation, there was a residual flow through the false lumen in the descending thoracic and abdominal aorta. Twenty months later, the patient complained of sudden back pain, and a CT scan demonstrated another new dissection at the distal edge of the open stent. Additionally, the false lumen that had remained since the onset of the type A aortic dissection enlarged during the observation period. An endovascular procedure was planned to exclude the false lumen. Despite closing all communicating channels between true and false lumen using a vascular plug, coils, and stent grafts, the false lumen continued to expand due to the residual flow at the visceral segment. The origin responsible for the flow was not identified. To perform an embolization of the false lumen, access into the false lumen was obtained by penetration of the dissected flap using a trans-septal needle. Following the successful penetration of the flap, embolization of the false lumen was performed using coils and glue. After the embolization, an angiogram of the false lumen confirmed the significant reduction of leakage into the true lumen. The size of the aorta and false lumen decreased after the embolization. Conclusion: Direct penetration of the dissected membrane of the aorta was a safe and useful measure for regaining access to the false lumen and for the following endovascular intervention.

Aneurysmal Degeneration of Fluoropolymer-Coated Paclitaxel-Eluting Stent in the Superficial Femoral Artery. A Rising Concern

Background: Although several clinical reports demonstrated a durable patency rate after a novel fluoropolymer-coated paclitaxel-eluting stent (Eluvia™; Boston Scientific, Marlborough, MA, USA) implantation, aneurysmal degeneration after implanting Eluvia™ has raised clinical concerns. Here, we report a case with exacerbated aneurysmal degeneration on serial angiography and intravascular ultrasound 50 months after Eluvia™ implantation for a superficial femoral artery lesion.Case presentation: A 79-year-old woman with claudication in the right lower extremity decreasing her quality of life was referred to our hospital. Pre-procedural angiography showed severe stenosis from the middle-to-distal part of the right superficial femoral artery, and Eluvia™ was implanted with optimal expansion. However, the patient had a recurrence of intermittent claudication in the right lower extremity 25 months thereafter. Angiography revealed de novo stenosis in the distal part of the popliteal artery and proximal stent edge restenosis at the Eluvia™ implantation site. Subsequently, the patient underwent endovascular therapy for these lesions. In addition, intravascular ultrasound at the time of endovascular therapy revealed vessel enlargement with a mean vessel diameter of 7.2-9.9 mm at the distal edge of the Eluvia™ implantation site. However, intermittent claudication on the right side recurred again 50 months after Eluvia™ implantation. Angiography demonstrated de novo severe stenosis from the distal part of the superficial femoral artery to the middle part of the popliteal artery. Furthermore, peri-stent contrast staining was found at the distal part of the Eluvia™ implantation site. Intravascular ultrasound showed a further enlargement of mean vessel diameter to 11.9 mm at the distal edge of the Eluvia™ stent. Moreover, enlargement of the lumen and stent malapposition were also found, suggesting exacerbated aneurysmal degeneration 50 months after Eluvia™ implantation.Conclusions: We report a case with exacerbated aneurysmal degeneration on serial angiography and intravascular ultrasound 50 months after Eluvia™ implantation for an SFA lesion. Long-term follow-up should be mandatory for patients receiving Eluvia™ implants.

The medial tangent of the proximal tibia is a suitable extra-articular landmark in determining the tibial anteroposterior axis

Background Tibial rotational alignment in total knee arthroplasty (TKA) is generally determined based on intra-articular structure, and can be difficult to ascertain in some cases. The aim of this study was to investigate whether the medial tangent angle of the tibia (MTAT) could be useful in determining the anteroposterior axis of the tibia. Methods This study was performed on 103 lower limbs in 53 patients who underwent primary total hip arthroplasty. The selection criteria for our study were based on the assumption that knees in patients undergoing THA exhibit fewer degenerative changes than knees in patients undergoing TKA. Using computed tomography images, the MTAT, comprising the medial tangent of the proximal tibia and the anteroposterior (AP) axis of the tibia, was measured on three horizontal planes: at the distal edge of the tibial tubercle (A), at 5 cm distally (B), and at 10 cm further distally (C). The tibial medial surface was grouped into three classes according to shape: valley type, flat type, and hill type. The percentage at which these shapes were observed in each group was also calculated. Measurement reliability was calculated using the intraclass correlation coefficient. Results The angles were 45.2° (interquartile range: IR 43.0–47.7) at A, 42.7° (IR 38.7–45.9) at B, and 42.4° (IR 38.2–45.9) at C. Intra-rater reliability and inter-rater reliability was 0.982 and 0.974 at A, 0.810 and 0.411 at B, and 0.940 and 0.811 at C, respectively. Regarding the tibial medial surface, the valley type was observed in all cases at A, and the hill type was observed in the highest percentage of cases at B and C. Conclusions The MTAT was approximately 45° at level A, and reproducibility was the highest among the three groups. The two points forming the valley on the tibial medial surface were bony ridges. Therefore, the medial tangent of the tibia at level A could be easily determined. Because the distal edge of the tibial tubercle exists at the surgical area and the extra-articular area, it can be a suitable intraoperative, extra-articular landmark in determining the tibial AP axis, even for revision TKA.

Deer antler extract potentially facilitates xiphoid cartilage growth and regeneration and prevents inflammatory susceptibility by regulating multiple functional genes

Background Deer antler is a zoological exception due to its fantastic characteristics, including amazing growth rate and repeatable regeneration. Deer antler has been used as a key ingredient in traditional Chinese medicine relating to kidney and bone health for centuries. The aim of this study was to dissect the molecular regulation of deer antler extract (DAE) on xiphoid cartilage (XC). Methods The DAE used in this experiment was same as the one that was prepared as previously described. The specific pathogen-free (SPF) grade Sprague-Dawley (SD) rats were randomly divided into blank group (n =10) and DAE group (n =10) after 1-week adaptive feeding. The DAE used in this experiment was same as the one that was prepared as previously described. The rats in DAE group were fed with DAE for 3 weeks at a dose of 0.2 g/kg per day according to the body surface area normalization method, and the rats in blank group were fed with drinking water. Total RNA was extracted from XC located in the most distal edge of the sternum. Illumina RNA sequencing (RNA-seq) in combination with quantitative real-time polymerase chain reaction (qRT-PCR) validation assay was carried out to dissect the molecular regulation of DAE on XC. Results We demonstrated that DAE significantly increased the expression levels of DEGs involved in cartilage growth and regeneration, but decreased the expression levels of DEGs involved in inflammation, and mildly increased the expression levels of DEGs involved in chondrogenesis and chondrocyte proliferation. Conclusions Our findings suggest that DAE might serve as a complementary therapeutic regent for cartilage growth and regeneration to treat cartilage degenerative disease, such as osteoarthritis.