Melanin-targeted [18F]-PFPN PET imaging may shed light for clear cell sarcoma.

PURPOSE: Intracytoplasmic melanin pigment is a characteristic of clear cell sarcoma (CCS), which is a particularly deadly type of soft-tissue sarcoma. [18F]-N-(2-(diethylamino)ethyl)-5-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)picolinamide ([18F]-PFPN) is a positron emission tomography (PET) probe characterized by high melanin affinity. Therefore, this study aimed to investigate the feasibility of melanin-targeted [18F]-PFPN PET in patients with CCS. METHODS: This prospective single-centre study recruited patients with pathologically confirmed CCS. [18F]-FDG PET/computed tomography and [18F]-PFPN PET/magnetic resonance imaging scans were performed within 1 week of each other. The lesion numbers and [18F]-FDG and [18F]-PFPN PET parameters (maximum standardized uptake value [SUVmax], mean standardized uptake value [SUVmean], metabolic/melanotic tumour volume [MTV/MLTV], and total lesion glycolysis/melanin [TLG/TLM]) were collected. RESULTS: Three patients with CCS were recruited and received PET imaging. A total of 56 lesions were detected on [18F]-PFPN PET, including primary tumour and distant metastases. Identical lesions were not detected on [18F]-PFPN and [18F]-FDG PET. Twelve lesions (12/39, 30.77%) on [18F]-FDG imaging were missed on [18F]-PFPN, and 20 lesions (20/47, 42.55%) on [18F]-PFPN imaging were missed on [18F]-FDG. In quantitative analysis, the [18F]-FDG SUVmean (4.60 ± 3.24) was higher than the [18F]-PFPN SUVmean (3.0 ± 2.63) in all lesions (P = 0.01). No significant correlations were found between the SUVmax, SUVmean, MLTV/MTV, and TLM/TLG values of [18F]-PFPN and [18F]-FDG (P > 0.05). CONCLUSION: Melanin-targeted [18F]-PFPN PET imaging is feasible for the diagnosis of CCS. Different imaging features were displayed on [18F]-PFPN and [18F]-FDG PET imaging, demonstrating the complementary role of the tracers. Combined use of the two imaging modalities would be preferred in patients with CCS. CLINICAL TRIAL REGISTRATION: NCT05963035.

Melanin-targeted [18F]-PFPN PET imaging for prognosticating patients with melanoma.

PURPOSE: Positron emission tomography (PET) using [18F]-PFPN, a melanin-targeted imaging tracer, has excellent diagnostic performance in patients with melanoma. This study aimed to investigate its value in prognostication and determine predictors of progression-free survival (PFS) and overall survival (OS). METHODS: We reviewed melanoma patients who underwent [18F]-PFPN and [18F]-FDG PET from February 2021 to July 2022. Clinical characteristics, follow-up data, and the following [18F]-PFPN PET parameters were recorded: maximum standardized uptake value (SUVmax), whole-body melanotic tumoral volume (WBMTV), and whole-body total lesion melanin (WBTLM). Receiver operating characteristic (ROC), Kaplan-Meier and Cox regression analyses were performed. RESULTS: Seventy-six patients (47 men and 29 women; mean age, 57.99 ± 10.72 years) were included for analysis. Median follow-up was 12.0 months (range: 1-22 months). Eighteen patients died and 38 experienced progression. Median OS was 17.60 months (95% confidence interval, 15.89-19.31). In the ROC analysis, [18F]-PFPN PET parameters were superior to those of [18F]-FDG PET in prognosticating death and disease progression. PFS and OS were significantly better in patients with lower SUVmax, WBMTV, and WBTLM on [18F]-PFPN PET (log-rank, P < 0.05). In the univariate analyses, distant metastasis, SUVmax, WBMTV, and WBTLM were significantly associated with cumulative incidence of PFS and OS (P < 0.05). In the multivariate analysis, SUVmax was an independent predictor of PFS and OS. CONCLUSIONS: [18F]-PFPN PET has a role in prognostication of melanoma patients. Patients with higher [18F]-PFPN SUVmax have worse prognosis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT05645484. Registered 9 December, 2022, https://clinicaltrials.gov/ct2/show/NCT05645484?cond=The+Prognostic+Value+of+18F-PFPN+PET+Imaging+in+Patients+With+Malignant+Melanoma&draw=2&rank=1.

COVID-19 and Computer Audition: An Overview on What Speech & Sound Analysis Could Contribute in the SARS-CoV-2 Corona Crisis.

At the time of writing this article, the world population is suffering from more than 2 million registered COVID-19 disease epidemic-induced deaths since the outbreak of the corona virus, which is now officially known as SARS-CoV-2. However, tremendous efforts have been made worldwide to counter-steer and control the epidemic by now labelled as pandemic. In this contribution, we provide an overview on the potential for computer audition (CA), i.e., the usage of speech and sound analysis by artificial intelligence to help in this scenario. We first survey which types of related or contextually significant phenomena can be automatically assessed from speech or sound. These include the automatic recognition and monitoring of COVID-19 directly or its symptoms such as breathing, dry, and wet coughing or sneezing sounds, speech under cold, eating behaviour, sleepiness, or pain to name but a few. Then, we consider potential use-cases for exploitation. These include risk assessment and diagnosis based on symptom histograms and their development over time, as well as monitoring of spread, social distancing and its effects, treatment and recovery, and patient well-being. We quickly guide further through challenges that need to be faced for real-life usage and limitations also in comparison with non-audio solutions. We come to the conclusion that CA appears ready for implementation of (pre-)diagnosis and monitoring tools, and more generally provides rich and significant, yet so far untapped potential in the fight against COVID-19 spread.

Computer Audition for Fighting the SARS-CoV-2 Corona Crisis-Introducing the Multitask Speech Corpus for COVID-19.

Computer audition (CA) has experienced a fast development in the past decades by leveraging advanced signal processing and machine learning techniques. In particular, for its noninvasive and ubiquitous character by nature, CA-based applications in healthcare have increasingly attracted attention in recent years. During the tough time of the global crisis caused by the coronavirus disease 2019 (COVID-19), scientists and engineers in data science have collaborated to think of novel ways in prevention, diagnosis, treatment, tracking, and management of this global pandemic. On the one hand, we have witnessed the power of 5G, Internet of Things, big data, computer vision, and artificial intelligence in applications of epidemiology modeling, drug and/or vaccine finding and designing, fast CT screening, and quarantine management. On the other hand, relevant studies in exploring the capacity of CA are extremely lacking and underestimated. To this end, we propose a novel multitask speech corpus for COVID-19 research usage. We collected 51 confirmed COVID-19 patients' in-the-wild speech data in Wuhan city, China. We define three main tasks in this corpus, i.e., three-category classification tasks for evaluating the physical and/or mental status of patients, i.e., sleep quality, fatigue, and anxiety. The benchmarks are given by using both classic machine learning methods and state-of-the-art deep learning techniques. We believe this study and corpus cannot only facilitate the ongoing research on using data science to fight against COVID-19, but also the monitoring of contagious diseases for general purpose.

Transparent PDMS Bioreactors for the Fabrication and Analysis of Multi-Layer Pre-vascularized Hydrogels Under Continuous Perfusion.

Tissue engineering in combination with stem cell technology has the potential to revolutionize human healthcare. It aims at the generation of artificial tissues that can mimic the original with complex functions for medical applications. However, even the best current designs are limited in size, if the transport of nutrients and oxygen to the cells and the removal of cellular metabolites waste is mainly dependent on passive diffusion. Incorporation of functional biomimetic vasculature within tissue engineered constructs can overcome this shortcoming. Here, we developed a novel strategy using 3D printing and injection molding technology to customize multilayer hydrogel constructs with pre-vascularized structures in transparent Polydimethysiloxane (PDMS) bioreactors. These bioreactors can be directly connected to continuous perfusion systems without complicated construct assembling. Mimicking natural layer-structures of vascular walls, multilayer vessel constructs were fabricated with cell-laden fibrin and collagen gels, respectively. The multilayer design allows functional organization of multiple cell types, i.e., mesenchymal stem cells (MSCs) in outer layer, human umbilical vein endothelial cells (HUVECs) the inner layer and smooth muscle cells in between MSCs and HUVECs layers. Multiplex layers with different cell types showed clear boundaries and growth along the hydrogel layers. This work demonstrates a rapid, cost-effective, and practical method to fabricate customized 3D-multilayer vascular models. It allows precise design of parameters like length, thickness, diameter of lumens and the whole vessel constructs resembling the natural tissue in detail without the need of sophisticated skills or equipment. The ready-to-use bioreactor with hydrogel constructs could be used for biomedical applications including pre-vascularization for transplantable engineered tissue or studies of vascular biology.

Verapamil inhibits scar formation after peripheral nerve repair in vivo.

The calcium channel blocker, verapamil, has been shown to reduce scar formation by inhibiting fibroblast adhesion and proliferation in vitro. It was not clear whether topical application of verapamil after surgical repair of the nerve in vivo could inhibit the formation of excessive scar tissue. In this study, the right sciatic nerve of adult Sprague-Dawley rats was transected and sutured with No. 10-0 suture. The stoma was wrapped with gelfoam soaked with verapamil solution for 4 weeks. Compared with the control group (stoma wrapped with gelfoam soaked with physiological saline), the verapamil application inhibited the secretion of extracellular matrix from fibroblasts in vivo, suppressed type I and III collagen secretion and increased the total number of axons and the number of myelinated axons. These findings suggest that verapamil could reduce the formation of scar tissue and promote axon growth after peripheral nerve repair.

The Distally Based Sural Flap for the Reconstruction of Ankle and Foot Defects in Pediatric Patients.

BACKGROUND: Skin and soft tissue defects at the level of the ankle and the heel remain a great challenge for plastic and reconstructive surgeons. There were just a few reports on the use of distal-based sural flap in pediatric patients. The purpose of this study was to introduce our experience in the treatment of skin and soft tissue defects of the pediatric feet by using this distally based sural neurocutaneous flap together with some technical modifications for a large-sized defect. METHODS: From July 2004 to October 2012, a total of 36 children younger than 12 years were treated with distally based sural flap for a variety of soft tissue defects of the foot and the ankle. All patients experienced a traffic accident. Thirty-four patients received standard distal-based reverse sural flaps, and 2 children received the flaps with nerve and vein sparing. RESULTS: The duration of follow-up varied from 3 to 48 months. All flaps survived completely. Two flaps presented vascular insufficiency and resulted in partial distal superficial necrosis (10%-20%). Two children had a compressive ulcer because of improper shoes wearing. There were no complaints related to the killing of the sural nerve. CONCLUSIONS: The distally based sural flap is an excellent choice in pediatric patients for covering defects of the lower leg and the foot because of its simplicity, versatility, low risk, and minimal donor site morbidity.

Hydrogels for Engineering of Perfusable Vascular Networks.

Hydrogels are commonly used biomaterials for tissue engineering. With their high-water content, good biocompatibility and biodegradability they resemble the natural extracellular environment and have been widely used as scaffolds for 3D cell culture and studies of cell biology. The possible size of such hydrogel constructs with embedded cells is limited by the cellular demand for oxygen and nutrients. For the fabrication of large and complex tissue constructs, vascular structures become necessary within the hydrogels to supply the encapsulated cells. In this review, we discuss the types of hydrogels that are currently used for the fabrication of constructs with embedded vascular networks, the key properties of hydrogels needed for this purpose and current techniques to engineer perfusable vascular structures into these hydrogels. We then discuss directions for future research aimed at engineering of vascularized tissue for implantation.

Dorsal plane-shaped advancement flap for the reconstruction of web space in syndactyly without skin grafting: A preliminary report.

BACKGROUND: Skin grafting for syndactyly repair is time-consuming, and it has the potential risks of scar contracture and web creep. Several techniques have been described for web reconstruction without skin grafts in simple syndactyly. Based on the hexagonal advancement flap, we designed a "plane-shaped" advancement flap on the dorsal hand or foot for a web reconstruction with primary closure. METHODS: Between June 2010 and August 2013, a "plane-shaped" advancement flap was used for web reconstruction in 24 syndactylies of 20 pediatric patients. The patients' age ranged from 1.5 to 8 years (mean age: 2.5 years). The patients were followed up for 15-48 months (mean: 28 months). RESULTS: The mean operation time was 60 min (range: 50-75 min). All incisions were closed primarily without skin grafting. All the flaps survived completely without early complications such as infection, vascular compromise or delayed healing. The mean hospitalization time was 3.5 days. There was no occurrence of long-term complications including web creep, flexion contractures, angulation deformity, or obvious keloid formation during the 15-48 months follow-up. Cosmetic and functional satisfactory outcomes were achieved in all cases without secondary revision. CONCLUSION: The dorsal plane-shaped advancement flap without skin graft is a solution for web space reconstruction in simple syndactyly, especially in the foot.

Free lateral great toe flap for the reconstruction of finger pulp defects.

INTRODUCTION: The aim of this study was to evaluate the esthetic and sensory outcomes after reconstruction of finger pulp defects with free toe flaps from the lateral aspect of the great toe. METHODS: From June 2006 to October 2011, we performed 48 free toe pulp transfers for finger pulp reconstruction in 43 patients; 18 male and 25 female patients with a mean age of 31.8 years (range, 16-47 years). Six patients suffered multiple digital pulp defects and five received two synchronous pulp transfers. The defects involved 20 thumbs, 15 index fingers, 10 long fingers, and 4 ring fingers, and flap size ranged from 24 × 18 to 55 × 30 mm. Follow-up evaluation included the functional and esthetic outcomes of the reconstructed pulps and donor toes. RESULTS: All but one flap survived completely. Overall, 32 cases (35 pulp flaps) were followed for more than 1 year (range, 12-48 months; average, 22.8 months). The Semmes-Weinstein sensitivity score was 2.83 to 4.74 at the flaps and the mean static two-point discrimination was 6.17 mm (range, 3-10 mm). A total of 13 patients (40.6%) experienced mild (10 cases) to moderate (3 cases) cold intolerance, and 1 patient (3.1%) suffered severe cold intolerance. According to the Michigan Hand Outcome Questionnaire the mean esthetic appearance score was 16 (range, 12-19). CONCLUSION: The free neurovascular great toe pulp flap is an efficient and reliable flap for the reconstruction of finger pulp defects.

Free conjoined or chimeric medial sural artery perforator flap for the reconstruction of multiple defects in hand.

BACKGROUND: One-stage coverage of multiple or jumping defects in the hand remains a great challenge in reconstructive surgery. A medial sural artery perforator-based conjoined or chimeric flap can be a potential candidate for reconstruction and a versatile donor site for tendon and nerve grafts. METHODS: Between September 2009 and December 2012, two free conjoined and three free chimeric medial sural artery perforator flaps were transferred to reconstruct multiple soft tissue defects in the hands. Only patients with more than two perforators in the preoperative Doppler analysis were admitted to this surgical approach. The anatomy, surgical technique, and clinical follow-up for up to 24 months are described. RESULTS: A variation of two to four perforators was found during dissection. All the flaps survived completely, and one patient developed wound dehiscence, which healed after continuous dressing changes. Two patients received tendon and nerve grafts simultaneously. Three donor sites received an additional free skin graft from the groin region. Follow-up of the five patients ranged from 6 to 24 months (mean 13 months) postoperatively. No obvious donor-site morbidity was observed. The patients were satisfied with the single-stage procedure and the aesthetic outcome of the hands. CONCLUSION: The free conjoined or chimeric medial sural artery perforator flap can provide a single-stage solution for multiple defects in the hand. The versatile donor site also provides the option to harvest a segment of a tendon or nerve graft for single-stage composite tissue reconstruction.

Modified technique for one-stage treatment of proximal phalangeal enchondromas with pathologic fractures.

PURPOSE: To evaluate the treatment outcome for enchondromas of the proximal phalanx with pathological fracture. METHODS: Between June 2008 and October 2012, we treated 9 patients with solitary proximal phalanx enchondromas and pathologic fractures by curetting the tumor, filling the void with a block of autogenous bone chip, and applying a low-profile miniplate. Postoperative follow-up included clinical assessment, pain evaluation, and radiographs. RESULTS: Follow-up time ranged from 13 to 42 months (mean, 30 mo). No major complications such as notable malalignment, nonunion, infection, or tumor recurrence were observed. All fractures healed after a mean of 8 weeks postoperatively. Full motion was achieved in 5 patients and extension lag (5° to 10°) of the proximal interphalangeal joint persisted in 4. Function was excellent in all patients according to the Takigawa criteria. All patients reported they were pain free and had resumed presurgical function within 12 weeks after surgery. CONCLUSIONS: Tumor curettage, reconstruction of the bone defect with a block of autogenous bone chip, and low-profile miniplate fixation provided one-stage treatment with immediate rigid stabilization and good functional outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Free distal ulnar artery perforator flaps for the reconstruction of a volar defect in fingers.

BACKGROUND: A volar defect in finger is a common manifestation in hand injuries, and proper volar coverage of fingers is of great significance for hand function and cosmetic appearance. PURPOSE: The aim of our study is to investigate the feasibility of reconstructing a volar defect in fingers with the free ipsilateral distal ulnar artery perforator flap under the brachial plexus block. METHODS: Eight free distal ulnar artery perforator flaps were used to reconstruct volar defects in eight fingers. The involved fingers were three index fingers, three long fingers, one thumb, and one ring finger. The sizes of flaps ranged from 3.0 × 4.0 to 3.0 × 11.0 cm. All the flaps were harvested from the ipsilateral forearm of the injured fingers. The donor sites were primarily closed except in one case with a skin graft. The operation time ranged from 120 to 150 min, with an average of 130 min. All the operations were performed under brachial plexus block. RESULTS: All flaps survived completely without any complications during the 4-18 months follow-up. All the patients were satisfied with the hand function and the cosmetic appearance. CONCLUSION: It might be a good workhorse flap to reconstruct the volar defects in fingers in hand surgery with the free distal ulnar artery perforator flaps.

Establishment of canine models of lunatomalacia through liquid nitrogen freezing.

The aim of this study was to investigate the feasibility of establishing dog models of lunatomalacia through liquid nitrogen freezing. Twelve adult crossbred dogs were divided into three groups. Unilateral lunates were peeled off the parenchyma and frozen to result in avascular necrosis. They were observed dynamically through X-ray, computed tomography (CT) and magnetic resonance imaging (MRI). Furthermore, gross and histomorphological observations of samples were performed. Disseminated punctate hyperintense images and abnormal manifestations were detected, respectively. At 12 weeks after surgery, uneven bone density of the lunate and a flattened lunate of irregular shape were detected. A large area of irregular hypointense foci and hyperintensity was observed. Gross sample observation revealed a large area of dead bone. A decrease in the density of the trabecular bones and several vacant bone lacunas were visible. Liquid nitrogen freezing is a successful and reliable method for preparing animal models of lunatomalacia.