Comparison of two self-nanoemulsifying drug delivery systems using different solidification techniques for enhanced solubility and oral bioavailability of poorly water-soluble celecoxib.

In this study, we aimed to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) and a solid self-nanoemulsifying granule system (S-SNEGS) to enhance the solubility and oral bioavailability of celecoxib. This process involved the preparation of a liquid SNEDDS (L-SNEDDS) and its subsequent solidification into a S-SNEDDS and a S-SNEGS. The L-SNEDDS consisted of celecoxib (drug), Captex® 355 (Captex; oil), Tween® 80 (Tween 80; surfactant) and D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS; cosurfactant) in a weight ratio of 3.5:25:60:15 to produce the smallest nanoemulsion droplet size. The S-SNEDDS and S-SNEGS were prepared with L-SNEDDS/Ca-silicate/Avicel PH 101 in a weight ratio of 103.5:50:0 using a spray dryer and 103.5:50:100 using a fluid bed granulator, respectively. We compared the two novel developed systems and celecoxib powder based on their solubility, dissolution rate, physicochemical properties, flow properties and oral bioavailability in rats. S-SNEGS showed a significant improvement in solubility and dissolution rate compared to S-SNEDDS and celecoxib powder. Both systems had been converted from crystalline drug to amorphous form. Furthermore, S-SNEGS exhibited a significantly reduced angle of repose, compressibility index and Hausner ratio than S-SNEDDS, suggesting that S-SNEGS was significantly superior in flow properties. Compared to S-SNEDDS and celecoxib powder, S-SNEGS increased the oral bioavailability (AUC value) in rats by 1.3 and 4.5-fold, respectively. Therefore, S-SNEGS wolud be recommended as a solid self-nanoemulsifying system suitable for poorly water-soluble celecoxib.

Modification of microenvironmental pH of nanoparticles for enhanced solubility and oral bioavailability of poorly water-soluble celecoxib.

This study aimed to develop a novel pH-modified nanoparticle with improved solubility and oral bioavailability of poorly water-soluble celecoxib by modifying the microenvironmental pH. After assessing the impact of hydrophilic polymers, surfactants and alkaline pH modifiers on the drug solubility, copovidone, sodium lauryl sulfate (SLS) and meglumine were chosen. The optimal formulation of solvent-evaporated, surface-attached and pH-modified nanoparticles composed of celecoxib/copovidone/SLS/meglumine at weight ratios of 1:1:0.2:0, 1:0.375:1.125:0 and 1:1:1:0.2:0.02, respectively, were manufactured using spray drying technique. Their physicochemical characteristics, solubility, dissolution and pharmacokinetics in rats were evaluated compared to the celecoxib powder. The solvent-evaporated and pH-modified nanoparticles converted a crystalline to an amorphous drug, resulting in a spherical shape with a reduced particle size compared to celecoxib powder. However, the surface-attached nanoparticles with insignificant particle size exhibited the unchangeable crystalline drug. All of them gave significantly higher solubility, dissolution, and oral bioavailability than celecoxib powder. Among them, the pH-modified nanoparticles demonstrated the most significant improvement in solubility (approximately 1600-fold) and oral bioavailability (approximately 4-fold) compared to the drug powder owing to the alkaline microenvironment formation effect of meglumine and the conversion to the amorphous drug. Thus, the pH-modified nanoparticle system would be a promising strategy for improving the solubility and oral bioavailability of poorly water-soluble and weakly acidic celecoxib.

Dense Pixel-Level Interpretation of Dynamic Scenes With Video Panoptic Segmentation.

A holistic understanding of dynamic scenes is of fundamental importance in real-world computer vision problems such as autonomous driving, augmented reality and spatio-temporal reasoning. In this paper, we propose a new computer vision benchmark: Video Panoptic Segmentation (VPS). To study this important problem, we present two datasets, Cityscapes-VPS and VIPER together with a new evaluation metric, video panoptic quality (VPQ). We also propose VPSNet++, an advanced video panoptic segmentation network, which simultaneously performs classification, detection, segmentation, and tracking of all identities in videos. Specifically, VPSNet++ builds upon a top-down panoptic segmentation network by adding pixel-level feature fusion head and object-level association head. The former temporally augments the pixel features while the latter performs object tracking. Furthermore, we propose panoptic boundary learning as an auxiliary task, and instance discrimination learning which learns spatio-temporally clustered pixel embedding for individual thing or stuff regions, i.e., exactly the objective of the video panoptic segmentation problem. Our VPSNet++ significantly outperforms the default VPSNet, i.e., FuseTrack baseline, and achieves state-of-the-art results on both Cityscapes-VPS and VIPER datasets. The datasets, metric, and models are publicly available at https://github.com/mcahny/vps.

Recurrent Temporal Aggregation Framework for Deep Video Inpainting.

Video inpainting aims to fill in spatio-temporal holes in videos with plausible content. Despite tremendous progress on deep learning-based inpainting of a single image, it is still challenging to extend these methods to video domain due to the additional time dimension. In this paper, we propose a recurrent temporal aggregation framework for fast deep video inpainting. In particular, we construct an encoder-decoder model, where the encoder takes multiple reference frames which can provide visible pixels revealed from the scene dynamics. These hints are aggregated and fed into the decoder. We apply a recurrent feedback in an auto-regressive manner to enforce temporal consistency in the video results. We propose two architectural designs based on this framework. Our first model is a blind video decaptioning network (BVDNet) that is designed to automatically remove and inpaint text overlays in videos without any mask information. Our BVDNet wins the first place in the ECCV Chalearn 2018 LAP Inpainting Competition Track 2: Video Decaptioning. Second, we propose a network for more general video inpainting (VINet) to deal with more arbitrary and larger holes. Video results demonstrate the advantage of our framework compared to state-of-the-art methods both qualitatively and quantitatively. The codes are available at https://github.com/mcahny/Deep-Video-Inpainting, and https://github.com/shwoo93/video_decaptioning.

Free Flaps for Soft Tissue Reconstruction of Digits.

Soft tissue reconstruction of the digit is challenging for hand surgeons because it must satisfy both functional and aesthetic requirements. A wide variety of treatment options exist. A free flap can be an alternative solution in some clinical situations. This article has 2 purposes. First, it discusses various considerations for free-flap usage for reconstruction of soft tissue defects of the digits and the available options. Second, it provides more detailed information regarding the 3 commonly used free flaps, namely, the partial toe pulp flap, radial artery superficial palmar branch flap, and arterialized venous flap.

The clinical result of arthroscopic bone grafting and percutaneous K-wires fixation for management of scaphoid nonunions.

The purpose of this study is to analyze the clinical results of patients with scaphoid nonunion treated with arthroscopic bone grafting and K (Kirschner)-wires fixation.We retrospectively reviewed the records of 27 patients with scaphoid nonunion who had been treated with arthroscopic bone grafting and K-wires fixation method from November 2008 to February 2014. The average patient age was 35 years. The time from injury to treatment averaged 45 months. The average follow-up period was 18 months. Bone union was assessed using serial plain radiographs. The functional outcome was evaluated by comparing the modified Mayo wrist score with the visual analog scale (VAS) for pain, which were measured at the time of preoperation and at final follow-up.Union was achieved in 26 of the 27 nonunions (96.29%). The average radiologic union time was 10 weeks. The average VAS score decreased from 6.38 (range, 3-10) preoperatively to 1.59 (range, 0-3) at the final follow-up. The average modified Mayo wrist score improved from 60.19 preoperatively to 83.46 at the final follow-up. According to this score, there were 12 excellent, 6 good, and 9 fair results at the final follow-up.Arthroscopic bone grafting and percutaneous K-wires fixation is an effective treatment method for a scaphoid nonunion and has the advantages of allowing thorough assessment, enabling a comprehensive management approach for scaphoid nonunion in a minimally invasive manner, and this method can also be used for the scaphoid nonunion with SNAC stage I.

Hand and Wrist Injuries in Golfers and Their Treatment.

A thorough understanding of the swing phases and mechanisms of injury in golf allows accurate diagnosis, treatment, and future prevention of injuries. Recommended initial treatment starts with cessation of practice to rest the wrist, a splint or orthotic brace, and nonsteroidal antiinflammatory drug medication with corticosteroid injection and swing modification. Pisiform excision is the best treatment of the most severe chronic cases of pisiform ligament complex syndrome. Delayed diagnosis of hook of hamate fracture may lead to complications, including flexor tendon rupture. Prompt surgical resection is recommended to hasten return to sport and to prevent further complications.

Recent Advances in Immediate Toe-to-Hand Transfer.

Toe-to-hand transfer is the last option for definitive reconstruction of the hand when digits have been lost as a result of traumatic amputations, congenital anomalies, or tumor ablation. Immediate toe-to-hand transfer for the treatment of acute hand injuries is defined as an emergency operation performed when replantation is impossible or failed. The aim of this article is to propose the indications, advantages and disadvantages of immediate toe to hand transfer as well as to compare the overall results with elective cases.

Management of complications relating to finger amputation and replantation.

There are many options in the management of fingertip or finger amputations. Injudicious revision amputation may cause complications. These complications can be prevented by tension-free closure of the amputation stump or primary coverage with appropriate flap. Replantation is the best way to keep the original length and maintain digital function. Patent vein repair or venous drainage with bleeding until neovascularization to the replanted part is the key to successful replantation. Prevention and management of complications in replantation and revision amputation increase patients' satisfaction and decrease costs. Research is needed to define new indications of replantation for digital amputation.

Delayed and suspended replantation for complete amputation of digits and hands.

PURPOSE: To analyze the clinical outcome for delayed or suspended replantation of complete amputations of digits or hands, or both. METHODS: We analyzed 20 cases involving 28 digital and 4 hand amputations that underwent delayed or suspended replantation. In 15 cases of single-digit amputation, patients underwent delayed replantation the morning following amputation. With amputation of multiple digits, bilateral digits, or the hand, the important digits or dominant hand underwent immediate replantation, and we suspended the surgeries for the residual digits or non-dominant hand, or both, until the next morning. We then evaluated the mean warm and cold ischemic time for the operations, graft survival rates, and clinical outcomes. The mean follow-up period was 26 months. We evaluated the clinical results using the criteria of Chen. RESULTS: The mean warm and cold ischemic times in 15 cases of delayed replantation were 2 hours 4 minutes and 7 hours 21 minutes, respectively. In 8 cases of suspended replantation, the mean warm and cold ischemic times in the first operation were 5 hours 54 minutes and 2 hours 36 minutes, respectively. In the second operation, the cold ischemic time averaged 15 hours 48 minutes. In this series, 24 of 28 digits and all 4 hands survived. Total survival incidence in both delayed and suspended replantation was 88%, not statistically different from the overall survival incidence in 711 cases of immediate replantation during the same period (84%). In delayed replantation, we observed an excellent result with 6 digits and a good result with another 6 digits. In suspended cases, we observed a good result with one multiple-digit and one hand procedure and we obtained a fair result in 3 multiple-digit and 2 hand replantation procedures. CONCLUSIONS: Delayed and suspended replantations demonstrate results comparable to immediate replantation regarding graft survival and clinical outcome. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Hand replantation with proximal row carpectomy.

The purpose of this study is to present our operative technique and postoperative results of the hand replantation with proximal row carpectomy in cases of complete amputation at the level of wrist joint. From May 2003 to April 2005, five patients suffered from complete amputation of the hand due to industrial trauma. Amputation level was radiocarpal joint in three cases and midcarpal joint in two cases. Three cases represented guillotine type and two cases with local crush type injuries. All were men and the mean age was 26.6 years. The mean follow-up period was 26.8 months. At the time of replantation, the wrist joint was stabilized with transarticular fixation using three to four Kirschner's wires after performing proximal row carpectomy. Postoperatively, functional results such as muscle strength, range of motion of the wrist and fingers, and sensory recovery were assessed according to Chen's criteria. Joint width and arthritic changes of the radio-capitate joint were evaluated with radiologic tools. According to Chen's criteria, the overall results in five cases were classified as grade II. Intrinsic muscle power of hands was found to be grade 4. The mean grip and pinch powers were 41% and 45%, respectively, compared to contralateral hand. The mean arc of flexion-extension of wrist was 53 degrees . Total mean active motion of fingers was 215 degrees. Static two-point discrimination of fingertip ranged from 8 to 13 mm. On the follow-up, computerized tomography showed well-preserved radio-capitate joint space without any arthritic changes. While performing hand replantation after amputation at the radiocarpal or midcarpal level, proximal row carpectomy is a useful procedure to preserve joint motion of the wrist in selected cases.

A retrospective analysis of 154 arterialized venous flaps for hand reconstruction: an 11-year experience.

BACKGROUND: The purpose of this study was to present the authors' 11-year clinical experience involving 154 cases of arterialized venous flaps for hand reconstruction. METHODS: The authors classified the venous flaps based on their size and composition. According to their size, flaps smaller than 10 cm were classified as small (n = 48), flaps larger than 25 cm were classified as large (n = 42), and those in between were classified as medium (n = 64). Classified according to their composition, there were 88 cases (57.1 percent) of venous skin flaps, 28 cases (18.2 percent) of innervated venous flaps, 15 cases (9.7 percent) of tendocutaneous venous flaps, and 17 cases (11 percent) of conduit venous flaps to repair arterial defects. There were six cases (3.9 percent) of composite venous flaps. RESULTS: The success rate of the flap transfer was 98.1 percent. The incidence of partial flap necrosis was 5.2 percent. The mean number of included veins was 2.17 for a small flap, 2.60 for a medium-sized flap, and 4.07 for a large flap (p < 0.01). The mean area of flap necrosis was 45.0 percent, 31.67 percent, and 18.75 percent for small, medium, and large flaps, respectively (p = 0.807). In eight cases of innervated venous flaps, the average static two-point discrimination was 10 mm (range, 8 to 15 mm). In 12 cases of tendocutaneous venous flaps, active range of motion at the proximal interphalangeal, distal interphalangeal, and metacarpophalangeal joints was 60, 20, and 75 degrees, respectively. CONCLUSIONS: The authors conclude that the arterialized venous flap is a valuable and effective tool for reconstructing complex hand injuries and may have a more comprehensive set of indications.

Immediate partial great toe transfer for the reconstruction of composite defects of the distal thumb.

BACKGROUND: Thumb defects distal to the interphalangeal joint do not cause any disability; therefore, any consideration to reconstruct the thumb is governed by the lifestyle and cultural background of the patient. This study presents the excellent results achieved by immediate partial great toe-to-hand transfer to reconstruct acute composite defects of the distal thumb. METHODS: Fifty-three patients with amputation or crush injury of the distal thumb who underwent partial great toe-to-hand transfer at the authors' institute over an 11-year period were reviewed. Based on the amputation level of the distal thumb, the authors classified the injuries into three groups. Operative techniques used were osteo-onychocutaneous flap with partial or whole toenail from the great toe and partial great toe transfer with arthrodesis of the interphalangeal joint. Overall results were evaluated in terms of success rate, incidence of emergency reexploration, and number and type of secondary operation. Static two-point discrimination, range of motion, pinch strength, and subjective satisfaction were also evaluated. RESULTS: The success rate of immediate partial great toe-to-hand transfer was 100 percent. The incidence of inflammation and the reexploration rate were not significantly different from those in previously reported articles. In 35 cases where postoperative follow-up was possible, static two-point discrimination, total active range of motion, and pinch strength were generally excellent and the majority of the patients were satisfied with the final outcome. CONCLUSION: Immediate reconstruction with partial great toe transfer is an excellent option for reconstruction of composite defects of the distal thumb, not only for aesthetic reasons but also for functional purposes.

A biomechanical comparison of four extensor tendon repair techniques in zone IV.

BACKGROUND: This study was designed to evaluate the biomechanical parameters of four different suture techniques specifically designed for zone IV extensor tendon injuries: the double figure of eight, the double modified Kessler, the six-strand double-loop, and the modified Becker suturing techniques. Ease of repair, tendon shortening, strength to 1-mm gap, strength to 2-mm gap, ultimate strength, and mode of repair failure were evaluated. METHODS: Twelve fresh-frozen cadaver hand-forearm units (48 fingers) were randomly assigned to the four suture repair treatments. The speed of tendon repair as performed by two matched-hand surgeons was recorded. Prerepair and postrepair tendon lengths were measured to document tendon shortening. The repair was stressed by linear distraction at 2.0 mm/minute using a servohydraulic frame. Video recordings of each distraction were independently reviewed for biomechanical parameters by three physician-observers in a double-blind setup. A one-way analysis of variance and t test analysis was performed. RESULTS: Results show that the double figure-of-eight technique and the double modified Kessler were significantly (p < 0.05) easier to perform at 7 minutes 31 seconds and 7 minutes 58 seconds, respectively, than the other two techniques. Tendon shortening ranged from 1.9 to 2.4 mm. There was no statistically significant difference in tendon shortening among the four techniques. Strength to 1-mm gap was significantly higher with the modified Becker technique, with a mean 28.8 +/- 8.0 N. This was followed by the six-strand double-loop technique, with 21.0 +/- 6.6 N, the double modified Kessler at 17.7 +/- 4.5 N, and the figure-of-eight technique at 17.5 +/- 2.4 N. Strength to 2-mm gap was significantly (p < 0.05) greater for the modified Becker technique and the modified Kessler technique at 56.0 +/- 9.2 N and 48.6 +/- 12.6 N, respectively, as compared with the other two suture methods. The modified Becker technique showed the highest ultimate strength at maximal loading at 63.3 +/- 7.8 N, followed by the double modified Kessler technique with strength of 56.8 +/- 14.8 N. Both were significantly stronger than the other two techniques. CONCLUSIONS: This study shows that the modified Becker suture technique, although not easily performed, proved to be the strongest repair, with a significantly greater resistance to 1-mm and 2-mm gap and the greatest ultimate strength on maximal loading.

Immediate toe-to-hand transfer in acute hand injuries: overall results, compared with results for elective cases.

In the past 5 years, 25 mutilated digits were reconstructed with immediate toe-to-hand transfers after acute hand injuries, for 21 patients. The overall results of the immediate toe-to-hand transfers were evaluated and compared with the results of 65 elective procedures performed during the same period by the same surgeon. There were 15 cases of great toe-to-hand transfer for thumb reconstruction, two cases of second toe transfer for index finger reconstruction, and four cases of simultaneous two-toe transfer for reconstruction of multiple-digit amputations. Two cases (two of 25 cases, 8 percent) were successfully salvaged with emergency reexploration. The incidences of emergency reexploration and postoperative infection were not significantly different from those for elective toe-to-hand transfer cases. The duration of industrial insurance coverage was much shorter than for elective cases, averaging 225 days (p < 0.001). Approximately 44 percent of the patients maintained their original jobs after immediate toe-to-hand transfer. The subjective satisfaction self-assessment scores of aesthetic appearance and function for the newly reconstructed thumb averaged 80 and 88 (of a total score of 100), respectively. Although satisfaction was lower than for elective reconstruction (p < 0.001), it was higher than for reconstruction of other digits. The donor-site appearance after great toe harvesting was mostly unsatisfactory. Immediate toe-to-hand transfer provides many advantages over the elective procedure in acute hand injuries, including single-stage reconstruction, shortened convalescence, early return to work, and socioeconomic efficiency. Because there were no significant differences in the success rates, frequencies of complications, or ultimate functional results, immediate toe-to-hand transfer is a safe and reliable procedure that is indicated for specific cases of acute digital amputation.