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BACKGROUND: Behavioral and neuropsychological functions are frequent longterm sequelae of severe traumatic brain injury (TBI). Neuropeptides, such as nerve growth factor (NGF), can enhance neurogenesis and improve cognitive functions after TBI, playing a pivotal role in neuroplasticity. A limited number of studies documented the safety and efficacy of intranasal NGF administration in children with severe TBI. CASE REPORT: A fourteen-year-old boy with a diffuse axonal injury secondary to severe TBI was treated with human-recombinant NGF administration. This patient underwent treatment with intranasal hr-NGF administration at a total dose of 50 gamma/kg, three times a day for seven consecutive days. The treatment schedule was performed for 4 cycles, at one month distance each. NGF administration improved radiologic functional assessment evaluated with positron emission tomography scan (PET) and single photon emission computed tomography (SPECT), with an important improvement in clinical conditions. Significant improvements were also observed, mainly in cognitive processes, memory, the planning of a communication strategy, execution skills, attention, and verbal expression. No side effects were reported. CONCLUSIONS: Additional studies are required to gain a deeper insight into this neurotrophin's neuroprotective function, but our findings reveal a potential efficacy of intranasal hr-NGF administration in enhancing cognitive and clinical outcomes among children with diffuse axonal injury after severe TBI. [ABSTRACT FROM AUTHOR]

Introduction: Tendon injures rank as the second most common hand injuries, and unsatisfactory repair can significantly impact a patient's everyday life. Over the years, various suture techniques have been studied in the pursuit of finding the optimal repair method. The ideal tendon repair should achieve maximum strength, while being easy to perform and minimizing tissue trauma. This study aims to compare the mechanical properties of the cross-locked U-Tang 4-strand suture to its unmodified version, the U-Tang 4-strand suture, to assess which technique offers greater repair strength., Methods: Sixteen Achilles tendons from New Zealand White rabbits were randomly assigned to one of two suture technique groups; an original U-Tang 4-strand suture or a cross-locked U-Tang 4-strand suture, both performed using a 4-0 Supramid thread. The specimens were tested in uniaxial tension after a preconditioning phase. Cross-sectional area, load until failure, gap formation, stiffness, elastic modulus, and failure stress were determined., Results: The standard U-Tang 4-strand suture withstood a maximum force of 25.48 ± 6.06 N, while the cross-locked version endured 33.90 ± 6.09 N. This indicates that the modified version demonstrated significantly greater strength (p = 0.021). The elastic modulus of the cross-locked U-Tang 4-strand suture (0.02 ± 0.003 MPa) was significantly higher than that of the original version (0.01 ± 0.006 MPa) (p = 0.028). No significant differences were observed regarding the cross-sectional area, load at 2 mm gap formation, stiffness and failure stress., Conclusion: Employing the cross-locked U-Tang 4-strand suture results in a significantly greater maximum force and elastic modulus compared to the original U-Tang 4-strand suture, utilizing the same thread and number of strands and knots. Therefore, the cross-locking version provides an alternative for achieving more stable initial repair strength., Competing Interests: The cadaver specimen were tendons from two previous studies, each of which had already undergone ethical review. They were collected from dead New Zealand White rabbits at the end-point. The veterinary application numbers were: ZH 115/2015 and ZH 090/2021. This corresponding project was licensed by the Animal Ethics Committee at local authorities in Switzerland (Canton Zurich ZH). Therefore, no additional veterinary application was required. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Johanna Buschmann reports financial support was provided by 10.13039/501100009396University Hospital Zurich. Johanna Buschmann reports a relationship with University Hospital Zurich that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The first set of data refers to PAR-2 gene expression with the target gene rbF2rl1 assessed in tenocytes harvested from New Zealand White Rabbits' Achilles tendons. These tenocytes were stimulated in vitro with 20 ng/mL platelet-derived growth factor-BB (PDGF-BB) and compared to the corresponding cell culture without growth factor PDGF-BB. In addition, three inhibitors were tested. In the presence or absence of 40 µM inhibitor concentration and 5 % fetal bovine serum, the following inhibitors were applied: SB203580 = inhibitor for MAPK; LY-294002 = inhibitor for PI3K; PD153035 = inhibitor for EGFR. As control, gene expression was assessed under DMSO = dimethyl sulfoxide (solvent of the inhibitors) or in medium = basal culture medium (with 10 % fetal bovine serum). The second set of data represents morphological aspects of cytoskeletal reorganization for rabbit Achilles tenocytes stimulated in vitro with 20 ng/mL PDGF-BB compared to the corresponding cell culture without PDGF-BB. Data on cell size, on F-actin immunohistochemical labeling intensity, α-tubulin immunohistochemical labeling intensity and on cell aspect ratio (length of the cell divided by its width) are presented. Moreover, analogous to the first set of data, cytoskeletal rearrangement in the presence or absence of the inhibitors SB203580, LY-294002 and PD153035 in the presence or absence of PDGF-BB were assessed., (© 2024 The Author(s).)

Background: Several surgical techniques have been reported for flexor tendon zone 1a-b lacerations without a clear consensus on the gold standard treatment. The purpose of this multicentre study was to measure the outcomes of zone 1a-b flexor tendon injuries treated with a pull-out suture (POS) versus direct suture (DS) technique., Patients and Methods: Fifteen patients were treated with the pull-out technique and 22 patients with a direct suture technique between 2014 and 2020. The controlled active motion (CAM) regimen protocol and a standardised follow-up schedule were used in both groups. Data on the demographics, surgery, and treatment characteristics were collected at baseline as well as at week 6 and 13 post-operatively. The primary outcome measurement was the complication rate. Secondary outcome measurements were reoperation rate, finger range of motion (ROM), strength as well as patient satisfaction., Results: The patient age ranged from 18 to 75 years in both groups with all patients having a complete FDP lesion after a clean-cut injury. The complication rate was 41% in the POS group and 16% in the DS group. The reoperation rate was 29% in the POS group and 8% in the DS group. Significant between-group differences in favour of the DS group were found in the passive DIP and passive PIP+DIP ROM at week 6 and week 13. Mean hand strength was 28.7 (11.6) kg in the POS group at week 13 and 21.3 (7.9) kg in the DS group. This difference was statistically significant (p=0.012) with a medium effect size (r=-0.41). Average patient satisfaction at week 13 was 7.5 (2.2) points in the POS and 7.7 (1.3) points in the DS group. The difference between groups was not significant (p=0.839)., Conclusion: This register-based study demonstrates lower complication and reoperation rates with the direct suture approach compared with a pull-out button technique. Although clinical results were similar between the two surgery techniques at week 13 post-surgery, a direct suture approach should always be attempted whenever possible. If necessary, other local structures should be included to increase suture strength and allow for early active motion rehabilitation regimens., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Multiple sclerosis (MS) disease-modifying treatments (DMTs) are tested in patients preselected for favorable risk/benefits ratios but prescribed broadly in clinical practice. We aimed to establish data-driven computations of individualized risk/benefit ratios to optimize MS care., Methods: We derived determinants of DMTs efficacy on disability progression from re-analysis and integration of 61 randomized, blinded Phase 2b/3 clinical trials that studied 46,611 patients for 91,787 patient-years. From each arm we extracted 80 and computed 30 features to identify and adjust for biases, and to use in multiple regression models. DMTs mortality risks were estimated from age mortality tables modified by published hazard ratios., Findings: Baseline characteristics of the recruited patients determine disability progression rates and DMTs efficacies with high effect sizes. DMTs efficacies increase with MS lesional activity (LA) measured by relapses or contrast-enhancing lesions and decrease with increasing age, disease duration and disability. Unexpectedly, as placebo arms' relapse rate rapidly declines with trial duration, efficacy of MS DMTs likewise decreases quickly with treatment duration. Conversely, DMTs morbidity/mortality risks increase with age, advanced disability, and comorbidities. We integrated these results into an interactive personalized web based DMTs risk/benefit estimator., Interpretation: Results predict that prescribing DMTs to patients traditionally excluded from MS clinical trials causes more harm than benefit. Treatment with high efficacy drugs at MS onset followed by de-escalation to DMTs that do not increase infectious risks would optimize risk/benefit. DMTs targeting mechanisms of progression independent of LA are greatly needed as current DMTs inhibit disability caused by LA only., Competing Interests: Potential Conflicts of Interest Nothing to report.

A major problem after tendon injury is adhesion formation to the surrounding tissue leading to a limited range of motion. A viable strategy to reduce adhesion extent is the use of physical barriers that limit the contact between the tendon and the adjacent tissue. The purpose of this study was to fabricate an electrospun bilayered tube of hyaluronic acid/polyethylene oxide (HA/PEO) and biodegradable DegraPol® (DP) to improve the anti-adhesive effect of the implant in a rabbit Achilles tendon full laceration model compared to a pure DP tube. Additionally, the attachment of rabbit tenocytes on pure DP and HA/PEO containing scaffolds was tested and Scanning Electron Microscopy, Fourier-transform Infrared Spectroscopy, Differential Scanning Calorimetry, Water Contact Angle measurements, and testing of mechanical properties were used to characterize the scaffolds. In vivo assessment after three weeks showed that the implant containing a second HA/PEO layer significantly reduced adhesion extent reaching levels comparable to native tendons, compared with a pure DP implant that reduced adhesion formation only by 20 %. Tenocytes were able to attach to and migrate into every scaffold, but cell number was reduced over two weeks. Implants containing HA/PEO showed better mechanical properties than pure DP tubes and with the ability to entirely reduce adhesion extent makes this implant a promising candidate for clinical application in tendon repair., Competing Interests: Declaration of competing interest The authors declare that they do not have any competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Measuring the outcome of peripheral nerve surgery is challenging because of the spectrum of functional impairment is dependent on the level and severity of the lesion. There are no nerve-specific patient-reported outcome measures, and no universally accepted outcome measurement both in terms of the parameters to be assessed and the methods and timing of the assessment. Nevertheless, the use of patient-reported outcome measures is fundamental to better understand the needs and expectations of patients, to take advantage of all treatment opportunities to offer the best possible support to these patients. This paper outlines current concepts in the measurement of outcome in peripheral nerve surgery., Competing Interests: Declaration of conflicting interestsThe authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Carpal tunnel syndrome (CTS) is the most common nerve entrapment disorder worldwide. The epidemiology and risk factors, including family burden, for developing CTS are multi-factorial. Despite much research, its intricate pathophysiological mechanism(s) are not fully understood. An underlying subclinical neuropathy may indicate an increased susceptibility to developing CTS. Although surgery is often performed for CTS, clear international guidelines to indicate when to perform non-surgical or surgical treatment, based on stage and severity of CTS, remain to be elucidated. Neurophysiological examination, using electrophysiology or ultrasonography, performed in certain circumstances, should correlate with the history and findings in clinical examination of the person with CTS. History and clinical examination are particularly relevant globally owing to lack of other equipment. Various instruments are used to assess CTS and treatment outcomes as well as the effect of the disorder on quality of life. The surgical treatment options of CTS - open or endoscopic - offer an effective solution to mitigate functional impairments and pain. However, there are risks of post-operative persistent or recurrent symptoms, requiring meticulous diagnostic re-evaluation before any additional surgery. Health-care professionals should have increased awareness about CTS and all its implications. Future considerations of CTS include use of linked national registries to understand risk factors, explore possible screening methods, and evaluate diagnosis and treatment with a broader perspective beyond surgery, including psychological well-being., (© 2024. Springer Nature Limited.)

Climbing is a fast-growing sport, with one of the most common injuries being a rupture of the finger flexor tendon pulley. The strain on pulleys increases as finger joints flex. However, to our knowledge, no study has conducted a kinematic analysis of climbers' fingers. Thus, this study aimed to examine finger kinematics during typical climbing tasks. Eleven elite climbers performed a sequence of four climbing moves, which were recorded by an optical motion capture system. Participants used crimp, half-crimp, and open-hand grips for three trials each, with the fourth condition involving campusing using any grip except crimp. Mean proximal interphalangeal joint (PIP) flexion during the holding phase was 87° (SD 12°), 70° (14°) and 39° (27°) for the crimp, half-crimp and open-hand grip, respectively. Hence, inter-individual PIP flexion ranges overlap between different gripping conditions. Two different movement patterns emerged in the open-hand grip, possibly influenced by the use of the little finger, leading to varying degrees of flexion in the middle and ring fingers. Avoiding little finger usage in the open-hand grip may reduce load during pulley rupture rehabilitation. The implications of PIP joint angle variability on individual pulley injury risk or prevention warrant further investigation. Motion capture proved effective for understanding finger kinematics during climbing and could guide future studies on pulley injury risk factors.

Large bone defects after trauma demand for adequate bone substitutes. Bone void fillers should be antibacterial and pro-angiogenic. One viable option is the use of composite materials like the combination of PLGA and amorphous calcium phosphate (aCaP). Copper stimulates angiogenesis and has antibacterial qualities. Either copper oxide (CuO) nanoparticles (NPs) were therefore added to PLGA/aCaP/CuO in different concentrations (1, 5 and 10 w/w %) or copper-doped tricalcium phosphate NPs (TCP with 2% of copper) were electrospun into PLGA/CuTCP nanocomposites. Bi-layered nanocomposites of PLGA/aCaP with different copper NPs (CuO or TCP) and a second layer of pristine PLGA were fabricated. Two clinical bacterial isolates ( Staphylococcus aureus and Staphylococcus epidermidis ) were used to assess antibacterial properties of the copper-containing materials. For angiogenesis, the chorioallantoic membrane (CAM) assay of the chicken embryo was performed. The higher the CuO content, the higher were the antibacterial properties, with 10 % CuO reducing bacterial adhesion most effectively. Vessel and cell densities were highest in the 5 % CuO containing scaffolds, while tissue integration was more pronounced at lower CuO content. The PLGA/aCaP/CuO (1 % CuO) behaved similar like PLGA/CuTCP in all angiogenic and antibacterial readouts, based on the same copper fraction. We conclude that CuO NPs or CuTCP NPs are useful components to increase angiogenic properties of nanocomposites and at the same time exhibiting antibacterial characteristics., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Johanna Buschmann reports financial support was provided by 10.13039/501100009396University Hospital Zurich. Johanna Buschmann reports a relationship with University Hospital Zurich that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The surgical repair of a ruptured tendon faces two major problems: specifically increased fibrous adhesion to the surrounding tissue and inferior mechanical properties of the scar tissue compared to the native tissue. Bacterial attachment to implant materials is an additional problem as it might lead to severe infections and impaired recovery. To counteract adhesion formation, two novel implant materials were fabricated by electrospinning, namely, a random fiber mesh containing hyaluronic acid (HA) and poly(ethylene oxide) (PEO) in a ratio of 1:1 (HA/PEO 1:1) and 1:4 (HA/PEO 1:4), respectively. Electrospun DegraPol (DP) treated with silver nanoparticles (DP-Ag) was developed to counteract the bacterial attachment. The three novel materials were compared to the previously described DP and DP with incorporated insulin-like growth factor-1 (DP-IGF-1), two implant materials that were also designed to improve tendon repair. To test whether the materials are prone to bacterial adhesion and biofilm formation, we assessed 10 strains of Staphylococcus aureus , Staphylococcus epidermidis , Pseudomonas aeruginosa, and Enterococcus faecalis , known for causing nosocomial infections. Fiber diameter, pore size, and water contact angle, reflecting different degrees of hydrophobicity, were used to characterize all materials. Generally, we observed higher biofilm formation on the more hydrophobic DP as compared to the more hydrophilic DP-IGF-1 and a trend toward reduced biofilm formation for DP treated with silver nanoparticles. For the two HA/PEO implants, a similar biofilm formation was observed. All tested materials were highly prone to bacterial adherence and biofilm formation, pointing toward the need of further material development, including the optimized incorporation of antibacterial agents such as silver nanoparticles or antibiotics.

Background: Robotic systems have successfully been introduced into other surgical fields in the past. First attempts with different setups are made in the field of microsurgery. The Symani® Surgical System, a flexible platform consisting of two robotic arms, features motion scaling with tremor filtration to address the demands and complexity of microsurgery. Symani's NanoWrist Instruments are the world's smallest, wristed surgical instruments, intended to improve a surgeon's range of motion beyond the capability of the human hand. This combination allows surgeons to scale their hand movements while seamlessly articulating the robotic micro instruments. Purpose: We report on our experience in extremity reconstruction with this novel system. Research Design: The Symani Surgical System ® was used for 6 cases of extremity reconstruction. The surgeon controlled the manipulators along with the footswitch while either sitting away from the operating table relying on 3D visualization with an exoscope or sitting at the operating table using a standard microscope. Data Collection: Microsurgical anastomoses were performed in 4 patients (3 end-to-end arterial anastomoses and one end-to-side arterial anastomosis) and nerve grafting was performed in 2 patients. Results: Microvascular anastomoses were slower vs conventional microsurgery, but all anastomoses were patent. Epineural coaptation showed proper fascicle alignment and tissue manipulation could be kept to a minimum. The platform's motion scaling allows the surgeon to perform precise micro-movements with only minimal tissue manipulation and hard-to-reach anatomy becomes accessible more easily. Conclusions: Robotic microsurgery might gain importance in the nearer future but more data will need to be collected., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Nicole Lindenblatt acts as a consultant and scientific advisor for Medical Microinstruments.

Background: Due to its partially superficial course, the superficial branch of the radial nerve is vulnerable to injury by trauma or surgery, potentially leading to painful neuroma. Surgical treatment is difficult. Among other factors, smoking and duration of pain before revision surgery have been suggested as risk factors for persistent pain after surgical revision, without concrete evidence. The aim of this study was therefore to identify factors influencing the outcome of revision surgery in SBRN neuropathic pain in our department., Methods: All 51 patients receiving revision surgery of the superficial branch of the radial nerve for neuropathic pain from 2010 to 2020 were contacted; 19 agreed to return for assessment. A medical chart review was performed to collect patient-, pain- and treatment-specific factors. Outcomes were recorded. In an outpatient consultation, clinical follow-up was performed and patients filled out the DASH, MHQ and painDETECT questionnaires., Results: After revision surgery, all patients experienced persistent pain. On multivariate logistic regression evaluating the risk of persistent pain, only smoking emerged as an independent risk factor. Age, gender, dominant side, location, time between trigger and surgery or diagnosis did not emerge as risk factors. No predictor for successful return to work could be identified., Conclusions: Treatment of painful neuroma of the superficial branch of the radial nerve is a challenge. Patients with neuropathic pain should be coached toward smoking cessation before neuroma surgery. Surgery can show benefit even after long symptom duration. No correlations between study clinical variables or test results and return to work could be identified, suggesting that other factors play a role in return to work., (Copyright © 2024 SFCM. Published by Elsevier Masson SAS. All rights reserved.)

The duodenum acts as a vital organ that performs fundamental physiological functions like digestion and nutrient absorption. Situated in the lower abdomen, the duodenum is located between the stomach and the jejunum. Usually, the duodenum is divided into four anatomical portions. We here compare paraffin embedded and cryosections of the healthy rabbit duodenum for research purposes. This analysis evaluates the differential outcomes resulting from the application of these fixation methodologies in conjunction with immunohistochemical assays targeting extracellular matrix markers collagen I, collagen III, fibronectin, α-smooth muscle actin (α-SMA), and proliferation marker ki67 as well as inflammatory marker PAR-2. Subsequent recommendations are provided based on our findings. Furthermore, the advantage of an antigen retrieval step in immunohistochemical labelling of paraffin sections was demonstrated and confirmed with an isotype negative control. Basic classical histological stainings as HE, GT and elastin were also performed. Comparison of different stainings and labellings was performed in serial sections, showing that adjacent to the circular muscle of the duodenum, the connective tissue was composed of collagen I and fibronectin, while the artery and vein walls were predominantly α-SMA positive. Moreover, PAR-2 immunohistochemical staining was performed, where particularly a type of gland adjacent to Brunner's glands showed prominent PAR-2 positive areas, while the Brunner's glands themselves were PAR-2 negative. Proliferating ki67 positive cells facing the lumen were highly abundant in all kinds of glands except for the Brunner's glands. This effort serves to furnish the research community with reference imagery pertinent to scientists opting for the rabbit duodenum model. The diversity of staining techniques employed herein establishes a foundational repository of images, primed for comparative analysis against pathological conditions. Furthermore, these images hold the potential to illustrate inter-species variations. For instance, they can be juxtaposed against murine or rat intestinal tracts, or even offer insights into the human context., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

In the oral cavity the tongue is an important muscular organ that supports the swallowing of food and liquids. It is responsible for the sense of taste, based on the many different taste buds it contains. Research in the field of tongue diseases demands for suitable preclinical models. The healthy rabbit tongue may therefore serve as baseline and reference for the pathological situation. With this consideration, we covered the fixation and histological stainings as well as the immunohistochemical labelling of the healthy rabbit tongue. In this technical note, initial choice of the fixative is discussed, with a comparison of formalin fixation and subsequent paraffin embedding versus cryopreservation. Moreover, we delineate the effect of an antigen retrieval step for formalin fixation by several examples. Finally, we provide ECM markers collagen I, collagen III, fibronectin, α-SMA and elastin staining as well as ki67 for proliferative status and PAR-2 protein expression as a marker for inflammatory status and nociception in tongue sections, mainly from the tongue body. Technically, we found superiority of paraffin sections for collagen I, collagen III, fibronectin, ki67 and α-SMA labelling, for selected detections systems. As for ECM components, the lamina propria was very rich in collagen and fibronectin, while the muscular body of the tongue showed only collagen and fibronectin positive areas between the muscle fibers. Moreover, α-SMA was clearly expressed in the walls of arteries and veins. The inflammatory marker PAR-2 on the other hand was prominently expressed in the salivary glands and to some extent in the walls of the vessels. Particular PAR-2 expression was found in the excretory ducts of the tongue. This technical note has the aim to provide baseline images that can be used to compare the pathological state of the diseased rabbit tongue as well as for inter-species comparison, such as mouse or rat tongue. Finally, it can be used for the comparison with the human situation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier GmbH.)

In this retrospective multicentre cohort study, we present the results of primary single-finger flexor tendon repairs in zones 1 to 3 between 2014 and 2021. Data from 218 patients were retrieved with their demographics, injury and surgery characteristics and therapy outcomes. The data were systematically collected and analysed at predefined time points up to 1 year after surgery. A good to excellent return of motion was achieved by 77% (Tang classification) and 92% (American Association for Surgery of the Hand classification) of patients at 1 year. The tendon rupture rate was 8.7%. Time had a significant impact on the recovery of finger motion and grip strength of up to 1 year, of patient satisfaction and upper extremity function up to 26 weeks, and of pain up to 13 weeks after surgery. Our results demonstrate that it is worthwhile to assess therapy outcomes over various measurement periods, as some outcomes may continue to improve up to 1 year after flexor tendon repair surgery. Level of evidence: III., Competing Interests: Declaration of conflicting interestsThe authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Situated in the oral cavity, the rabbit palatine tonsils are part of the mucosal immune system and help to defend the body against foreign pathogens. Expressed as two oval protrusions in the wall of the oropharynx, the rabbit palatine tonsils are characterized by excretory ducts and trabeculae. We here compare paraffin embedded and cryosections of the healthy rabbit tonsils. This analysis centers on evaluating the differential outcomes resulting from the application of these fixation methodologies in conjunction with immunohistochemical assays targeting collagen I, collagen III, fibronectin, α-smooth muscle actin (α-SMA), and ki67. Subsequent recommendations are provided based on our findings. Furthermore, we demonstrate the advantage of an antigen retrieval step in immunohistochemical labeling of paraffin sections. Basic classical histological stainings as HE, GT and elastin were also performed. Comparison of different stainings and labelings was furthermore performed in serial sections, showing that adjacent to the excretory ducts, the tonsillar tissue was particularly composed of collagen I and fibronectin, while the vessel walls were predominantly α-SMA positive. Moreover, PAR-2 immunohistochemical staining was performed, where a small fraction of the cells found in the tonsillar connective tissue were PAR-2 positive (probably a subpopulation of mast cells), as well as the lumen of some excretory ducts and trabeculae. Collagen III on the other hand was only weakly expressed in the tonsils. Proliferating ki67 positive cells were rare. This endeavor serves to furnish the scientific community with reference imagery pertinent to researchers opting for the rabbit palatine tonsil model. The diversity of staining techniques employed herein establishes a foundational repository of images, primed for comparative analysis against pathological conditions. Furthermore, these images hold the potential to illustrate inter-species variations. For instance, they can be juxtaposed against murine or rodent tonsils, or even offer insights into the human context., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

The aim of this paper is to offer a narrative review of the literature regarding the influence of transition metals on angiogenesis, excluding lanthanides and actinides. To our knowledge there are not any reviews up to date offering such a summary, which inclined us to write this paper. Angiogenesis describes the process of blood vessel formation, which is an essential requirement for human growth and development. When the complex interplay between pro- and antiangiogenic mediators falls out of balance, angiogenesis can quickly become harmful. As it is so fundamental, both its inhibition and enhancement take part in various diseases, making it a target for therapeutic treatments. Current methods come with limitations, therefore, novel agents are constantly being researched, with metal agents offering promising results. Various transition metals have already been investigated in-depth, with studies indicating both pro- and antiangiogenic properties, respectively. The transition metals are being applied in various formulations, such as nanoparticles, complexes, or scaffold materials. Albeit the increasing attention this field is receiving, there remain many unanswered questions, mostly regarding the molecular mechanisms behind the observed effects. Notably, approximately half of all the transition metals have not yet been investigated regarding potential angiogenic effects. Considering the promising results which have already been established, it should be of great interest to begin investigating the remaining elements whilst also further analyzing the established effects., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Purpose: Trapeziectomy has frequently been used to treat basal thumb osteoarthritis. However, complications, such as shortening of the thumb ray and reduced mobility and strength, can occur. The aim of this study was to present a 10-year follow-up of distraction arthroplasty without trapeziectomy., Methods: Fifteen patients were followed for a mean of 121 months (range, 121-124 months). Subjective outcomes were evaluated with the Disabilities of the Arm, Shoulder, and Hand questionnaire, while the pain intensity was assessed with a Visual Analog Scale both before surgery and at the end of follow-up. Objective outcomes were obtained using the Kapandji score and an assessment of grip and pinch strength. Preoperative and final postoperative x-rays were obtained to evaluate metacarpal subsidence and progression of trapezial-metacarpal joint arthritis., Results: The Visual Analog Scale score was reduced from 9.4 ± 0.5 before surgery to 2.5 ± 1 at follow-up. The mean Disabilities of the Arm, Shoulder, and Hand questionnaire score was 75.6 ± 12.6 before surgery and 16.9 ± 4 at 10 years. Hand grip strength of the operated side (26 ± 5.5 kg) achieved 95% of functionality compared to the opposite side, while key pinch strength (6.4 ± 1.6 kg) reached 93%. A Kapandji opposition score of 10 points was found in 12 patients, a score of 9 was found in 1, and a score of 8 was found in 2., Conclusions: Distraction arthroplasty of the trapeziometacarpal joint ensures good results in long-term follow-up, when performed in patients with stage I-II basal thumb osteoarthritis., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2023. Published by Elsevier Inc.)

Background: The purpose of this study is to assess outcomes in flexor pollicis longus tendon repairs with 6-strand core sutures with and without circumferential sutures., Methods: A 6-strand core suture technique with and without circumferential sutures was used. Thirty-three patients were summarized in the C group (circumferential group) and 16 patients in the NC group (non-circumferential group). After the surgery, the wrist was stabilized with a dorsal blocking splint and a controlled early active motion protocol was applied. At weeks 6, 13, and 26 data on demographics, type of injury, surgery, postoperative rehabilitation, complications such as re-rupture and the following outcome measurements were collected: range of motion and its recovery according to the Tang criteria, Kapandji score, thumb and hand strengths, Disabilities of the Arm, Shoulder and Hand score, and satisfaction., Results: There were no significant differences in range of motion and strength between the 2 treatment groups. In both groups, the outcome measurements increased over time and they expressed similar satisfaction with the surgical treatment. In 4 patients of the C group tendon repair ruptured and in 1 patient of the NC group., Conclusions: Six-strand repair technique is an effective procedure to assure early active motion after flexor pollicis longus tendon injuries and good results can also be achieved by omitting the circumferential suture.

Tendon injuries can result in two major drawbacks. Adhesions to the surrounding tissue may limit the range of motion, while fibrovascular scar formation can lead to poor biomechanical outcomes. Prosthetic devices may help to mitigate those problems. Emulsion electrospinning was used to develop a novel three-layer tube based on the polymer DegraPol (DP), with incorporated insulin-like growth factor-1 (IGF-1) in the middle layer. Scanning electron microscopy was utilized to assess the fiber diameter in IGF-1 containing pure DP meshes. Further characterization was performed with Fourier Transformed Infrared Spectroscopy, Differential Scanning Calorimetry, and water contact angle, as well as through the assessment of mechanical properties and release kinetics from ELISA, and the bioactivity of IGF-1 by qPCR of collagen I , ki67, and tenomodulin in rabbit Achilles tenocytes. The IGF-1-containing tubes exhibited a sustained release of the growth factor up to 4 days and showed bioactivity by significantly upregulated ki67 and tenomodulin gene expression. Moreover, they proved to be mechanically superior to pure DP tubes (significantly higher fracture strain, failure stress, and elastic modulus). The novel three-layer tubes intended to be applied over conventionally sutured tendons after a rupture may help accelerate the healing process. The release of IGF-1 stimulates proliferation and matrix synthesis of cells at the repair site. In addition, adhesion formation to surrounding tissue can be reduced due to the physical barrier.

Introduction: The influence of pain and a concomitant digital nerve injury on the course of rehabilitation after flexor tendon injury remains ambiguous. The objectives of the study were to: i) analyse the evolution of pain spanning one year after a primary flexor tendon repair in zones 1-3; ii) examine the differences in pain levels in patients with and without digital nerve injury; and iii) evaluate the relationship between pain, digital nerve injury and pain medication, total active motion (TAM), DASH scores and patient satisfaction., Methods: Data from 189 patients were retrieved from a flexor tendon registry between 2014 and 2020. Differences in pain, TAM, DASH and patient satisfaction were analysed. Multiple linear and binary logistic regression analyses were performed to determine the relationship between clinical outcomes., Results: Pain significantly decreased in the course of rehabilitation ( p < 0.001 to 0.006). No relationship could be identified between nerve injury and pain ( p = 0.21-0.97). In week 6, the presence of pain and a nerve injury were significantly associated with lower TAM scores ( p = 0.001). In week 13, pain during motion ( p < 0.001) and the presence of a nerve injury ( p = 0.036) were significantly associated with worse DASH scores. Patient satisfaction was significantly inversely correlated to pain during motion in weeks 13 and 26 ( p < 0.001)., Conclusion: We found a significant relationship between pain during motion and pain medication intake, TAM, DASH scores and patient satisfaction. It is therefore advisable to closely monitor this parameter after flexor tendon injuries., Study Registration: This multi-center cohort study is registered under https://clinicaltrials.gov: NCT04312412., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

This study aimed to analyse which factors contribute to pain and limited hand function after dorsal wrist ganglion excision. We included 308 patients who underwent surgery between September 2017 and August 2021. Patients completed baseline questionnaires and the patient-rated wrist/hand evaluation questionnaire at baseline and 3 months postoperatively. We observed an improvement in postoperative pain and hand function, but individual outcomes were highly variable. We performed stepwise linear regression analyses to examine which patient characteristics, disease characteristics and psychological factors were associated with postoperative pain and hand function. Higher postoperative pain intensity was associated with recurrence following previous surgery, treatment of the dominant hand, higher baseline pain intensity, lower credibility the patient attributes to the treatment and longer symptom duration. Worse hand function was associated with recurrence following prior surgery, worse baseline hand function and lower treatment credibility. Clinicians should take these findings into account during patient counselling and expectation management. Level of evidence: II.

Purpose: The aims of this retrospective cohort study were to present outcomes of zone 2 and 3 primary flexor tendon repairs and to evaluate how clinical outcomes change over time within and between zones of injury at weeks 6, 13, and 26., Methods: Data were retrieved from a multicenter flexor tendon cohort registry from 2014 to 2021. The inclusion criteria were: (1) adult patients after primary flexor tendon surgery in zone 2 or 3, (2) flexor digitorum profundus laceration of >50%, (3) 4-6 multistrand flexor digitorum profundus core suture, and (4) early active motion protocol. The primary outcome was the range of motion. Secondary outcomes were strength, patient satisfaction on an 11-point Likert scale, and self-reported physical function measured with the Disability of the Arm, Shoulder, and Hand questionnaire 6, 13, and 26 weeks after surgery., Results: We evaluated 33 patients after 39 tendon repairs in zone 3 and 174 repairs in zone 2 of 163 patients. Range of motion significantly improved over time in both zones ( P < .001 to .01). Between-group range of motion differences were nonsignificant except for week 26 ( P < .001) for the zone 3 group. Hand strength significantly improved in both zones over time ( P < .001 to .01), while between-zone strength differences were statistically nonsignificant ( P  = .37 to .93). Patient satisfaction was generally good to high (mean 6.8 to 8.0 points) with significant within-group changes in both zones ( P < .001). There were no relevant between-zone differences in Disability of the Arm, Shoulder, and Hand scores at any time point., Conclusions: Patients had significantly improved clinical outcomes in both zones. The zone of injury significantly affected the total active motion scores at the final assessment after 26 weeks for the zone 3 injuries. For the secondary outcomes hand strength, patient satisfaction, and Disability of the Arm, Shoulder, and Hand scores, we discovered no significant between-group differences., Type of Study/level of Evidence: Therapeutic IV., (© 2023 The Authors.)

Adipose tissue presents a comparably easy source for obtaining stem cells, and more studies are increasingly investigating the therapeutic potential of adipose-derived stem cells. Wound healing, especially in chronic wounds, and treatment of skin diseases are some of the fields investigated. In this narrative review, the authors give an overview of some of the latest studies concerning wound healing as well as treatment of several skin diseases and concentrate on the different forms of application of adipose-derived stem cells., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Different factors have to be considered and weighted in the treatment algorithm of lower extremity reconstruction. A combination of both clinicians' and patients' perspectives is necessary to provide a conclusive picture. Currently, there aren't any standardized and validated measurement data sets for lower extremity reconstructions. This makes it necessary to identify the relevant domains. We, therefore, performed a systematic review and metanalysis of outcome measurements and evaluated their ability to measure outcomes after lower extremity reconstruction. A systematic review and metanalysis according to the 'Preferred Reporting Items for Systematic Reviews and Meta-Analyses' protocol were performed for studies reporting at least one structured outcome measurement of lower extremity reconstruction. Both Patient (PROMs)- and Clinician reported outcome measurements (CROMs)were analyzed. Of the 2827 identified articles, 102 were included in the final analysis. In total 86 outcome measurements were identified, 34 CROMs, 44 PROMs and 8 (9.3%) outcome measurements that have elements of both. Twenty-four measure functional outcome, 3 pain, 10 sensations and proprioception, 9 quality of life, 8 satisfaction with the result, 5 measure the aesthetic outcome, 6 contours and flap stability and 21 contain multidomain elements. A multitude of different outcome measurements is currently used in lower extremity reconstruction So far, no consensus has been reached on what to measure and how. Validation and standardization of both PROMs and CROMs in plastic surgery is needed to improve the outcome of our patients, better meet their needs and expectations and eventually optimize extremity reconstruction by enabling a direct comparison of studies' results.

Bite Injuries - Diagnosis and Treatment Abstract. In Switzerland 50% of the people get bitten by an animal once in their lifetime. Almost 20% of all bite injuries lead to infections. All bite wounds should be debrided and irrigated with saline. Primary wound management is critical in terms of reducing the risk of infection. Injuries to the hands and face should be treated by a hand or plastic surgeon.

The anatomy and technique of free muscle flaps - in particular gracilis flap and latissimus dorsi flap - in lower extremity reconstruction have been well described. There is a paucity of data on potential risk factors in larger patient series that affect the outcome. The objective of this study was to address this lack of knowledge by reporting outcomes and complications of free muscle flaps as a primary option in lower extremity reconstruction. From 2009 to 2020, a total of 253 consecutive patients with soft tissue defects of the lower limb from trauma, infection or malignancies underwent lower extremity reconstructive surgery with 266 free muscle flaps. Complications requiring revision surgery were noted in 36.1% of cases. Total flap loss occurred in 10.5% of cases. Patients requiring revision surgery were older, more likely to be female, more likely to be active smokers, and more likely to have a higher ASA score. Lower extremity reconstruction with free muscle flaps has a relevant complication rate that both patient and reconstructive surgeon need to be aware of. Prospective studies should try to further assess the factors affecting the outcome.

Tendon injuries suffer from a slow healing, often ending up in fibrovascular scar formation, leading to inferior mechanical properties and even re-rupture upon resumption of daily work or sports. Strategies including the application of growth factors have been under view for decades. Insulin-like growth factor-1 (IGF-1) is one of the used growth factors and has been applied to tenocyte in vitro cultures as well as in animal preclinical models and to human patients due to its anabolic and matrix stimulating effects. In this narrative review, we cover the current literature on IGF-1, its mechanism of action, in vitro cell cultures (tenocytes and mesenchymal stem cells), as well as in vivo experiments. We conclude from this overview that IGF-1 is a potent stimulus for improving tendon healing due to its inherent support of cell proliferation, DNA and matrix synthesis, particularly collagen I, which is the main component of tendon tissue. Nevertheless, more in vivo studies have to be performed in order to pave the way for an IGF-1 application in orthopedic clinics.

Heart failure poses a big health problem and may result from obesity, smoking, alcohol and/or growing age. Studying pathological heart tissue demands accurate histological and immunohistochemical stainings in animal models, including chromogenic and fluorescent approaches. Moreover, a reliable set of healthy heart stainings and labeling are required, in order to provide a reference for the pathological situation. Heart and brain tissue of a healthy rabbit were collected, and different histological key steps were compared, such as paraffin embedding after formalin fixation versus cryopreservation; an antigen retrieval (AR) step in processing paraffin sections versus the same procedure without AR; or a chromogenic with a fluorescent detection system, respectively. Using serial sections, we stained the same morphological structure with classic approaches (HE, Masson Goldner Trichrome (GT) and Elastica van Gieson (EL)) and with different markers, including collagen I, collagen III, fibronectin, α-SMA, protease-activated receptor-2 (PAR-2) which is an inflammation-related marker, and ki67 for proliferating cells. Differences between conditions were quantitatively assessed by measuring the color intensity. Generally, cryosections exhibited a more prominent signal intensity in immunohistochemically labeled sections than in paraffin sections, but the strong staining was slurry, which sometimes impeded proper identification of morphological structures, particularly at higher magnifications. In addition, the advantage of an AR step was observed when compared to the condition without AR, where signal intensities were significantly lower. Different stainings of the heart arteries and the myocardium revealed a clear distribution of extracellular matrix components, with prominent collagen III in the artery wall, but an absence of collagen III in the myocardium. Moreover, paraffin-embedded sections provided more distinct structures compared to cryosections after collagen III, ki67, fibronectin, and α-SMA labeling. As for the Purkinje cells that were depicted in the heart and the cerebellum (Purkinje neurons), we found GT staining most suitable to depict them in the heart, while HE as well as EL staining was ideal to depict Purkinje neurons in the cerebellum. In sum, we provide useful reference images with different stainings for researchers using the rabbit heart or brain model. Such images can help to decide which of the immunohistochemical protocols are valuable to reach a specific aim. Recommendations are given for the best visualization of the target structures and specific (immunohistochemical) staining., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Sural nerve neuroma is often caused by an injury during prior surgery, for example, osteosynthesis or ligament refixations at ankle level. Different surgical techniques to treat neuroma have been described. Neurectomy of an injured symptomatic sural nerve has been described as a treatment option for neuropathic pain. The aim of this study was to evaluate the outcomes of this technique to operatively treat sural nerve neuroma in our department., Methods: From 2010 to 2020, a total of 30 consecutive patients with neuropathic pain and suspected neuroma of the sural nerve underwent sural nerve neurectomy. A medical chart review was performed to collect patient-, pain-, and treatment-specific factors. Outcomes were registered., Results: After neurectomy, 22 patients (73.3%) had persisting pain. In logistic regression models evaluating the risk of persisting pain after sural nerve neurectomy, no independent predictor of higher risk of persisting pain could be identified., Conclusion: For sural nerve neuromas, neurectomy remains an option as the surgical morbidity is minor, but patients need to be counseled that only a fourth of those undergoing surgery will be pain-free afterward., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Human lung cancer ranks among the most frequently treated cancers worldwide. As copper appears critical to angiogenesis and tumor growth, selective removal of copper represents a promising strategy to restrict tumor growth. To this end, we explored the activity of the novel high-affinity membrane-permeant Cu(I) chelator PSP-2 featuring a low-zeptomolar dissociation constant. Using H460 human lung cancer cells, we generated small tumors on the chorioallantoic membrane of the chicken embryo (CAM assay) and studied the effects of topical PSP-2 application on their weight and vessel density after one week. We observed a significant angiosuppression along with a marked decrease in tumor weight under PSP-2 application compared to controls. Moreover, PSP-2 exposure resulted in lower ki67 + cell numbers at a low dose but increased cell count under a high dose. Moreover, HIF-1α + cells were significantly reduced with low-dose PSP-2 exposure compared to high-dose and control. The total copper content was considerably lower in PSP-2 treated tumors, although statistically not significant. Altogether, PSP-2 shows promising potential as an anti-cancer drug. Nevertheless, further animal experiments and application to different tumor types are mandatory to support these initial findings, paving the way toward clinical trials.

Introduction  The purpose of the study was to evaluate the results of treatment of the nonunion of long bones using nonvascularized iliac crest grafts (ICGs) or vascularized bone grafts (VBGs), such as medial femoral condyle corticoperiosteal flaps (MFCFs) and fibula flaps (FFs). Although some studies have examined the results of these techniques, there are no reports that compare these treatments and perform a multifactorial analysis. Methods  The study retrospectively examined 28 patients comprising 9 women and 19 men with an average age of 49.8 years (range: 16-72 years) who were treated for nonunion of long bones between April 2007 and November 2018. The patients were divided into two cohorts: group A had 17 patients treated with VBGs (9 patients treated with MFCF and 8 with FF), while group B had 11 patients treated with ICG. The following parameters were analyzed: radiographic patterns of nonunion, trauma energy, fracture exposure, associated fractures, previous surgeries, diabetes, smoking, age, and donor-site morbidity. Results  VBGs improved the healing rate (HR) by 9.42 times more than the nonvascularized grafts. Treatment with VBGs showed a 25% decrease in healing time. Diabetes increased the infection rate by 4.25 times. Upper limbs showed 70% lower infection rate. Smoking among VBG patients was associated with a 75% decrease in the HR, and diabetes was associated with an 80% decrease. Conclusion  This study reports the highest success rates in VBGs. The MFCFs seem to allow better clinical and radiological outcomes with less donor-site morbidity than FFs., Competing Interests: Conflict of Interest The authors declared no potential conflict of interest with respect to the research, authorship, and/or publication of this article. Dr. Calcagni reports nonfinancial support from Sobi, nonfinancial support from Medartis, nonfinancial support from Silk Biomaterials, nonfinancial support from DyCare, outside the submitted work., (Society of Indian Hand Surgery & Microsurgeons. All rights reserved.)

Background and Objectives: Retrograde free venous flaps represent a separate entity among free venous flaps: their physiology is still unclear, but they provide an immediate visible refill after reconnection, with a similar behaviour to conventional flaps. Therefore, the dimensions and the indications of these flaps can be extended beyond what was previously believed, and they can be easily customized, including with respect to tendons and nerves. Nevertheless, they are still debated and regarded as unsafe. Materials and Methods: From 2012 to 2019, we performed 31 retrograde free venous flaps on 31 patients to reconstruct hands, digits, and in one case the heel. All the flaps were arterialized in a retrograde manner; the donor site was the forearm in 28 cases, the foot in 2 cases, and the calf in 1 case. We recorded the size, vein architecture, donor site, donor artery, donor morbidity, function for composite and non-composite flaps, immediate complications, late complications, survival rate, and the number of revisions. We recorded the hand function when appropriate. A total of 10 flaps were also intraoperatively studied with indocyanine green to monitor their hemodynamical behaviour. Results: All the patients were followed for an average of 8 months (6−15). The flap dimensions ranged from 6 cm2 to 136 cm2. All the flaps, except two that had complete necrosis, survived. Two flaps had partial necrosis. There was no correlation between necrosis and the size of the flap, with one case of necrosis and one of partial necrosis in the small flaps (<10 cm2). None of the cases with partial necrosis needed a new flap. Two flaps developed a late arterio-venous shunt that was ligated. Conclusions: The retrograde free venous flaps proved to be a useful tool for complex reconstructions of the hand and extremities. They can provide a large island of pliable skin and composite tissue with tendons and nerves, but surgeons must be aware of some caveats., Competing Interests: The authors declare no conflict of interest.

(1) Background: Surgical tendon repair often leads to adhesion formation, leading to joint stiffness and a reduced range of motion. Tubular implants set around sutured tendons might help to reduce peritendinous adhesions. The lubricant hyaluronic acid (HA) is a viable option for optimizing such tubes with the goal of further enhancing the anti-adhesive effect. As the implant degrades over time and diffusion is presumed, the impact of HA on tendon cells is important to know. (2) Methods: A culture medium of rabbit Achilles tenocytes was supplemented with high-molecular-weight (HMW) HA and the growth curves of the cells were assessed. Additionally, after 3, 7 and 14 days, the gene expression of several markers was analyzed for matrix assembly, tendon differentiation, fibrosis, proliferation, matrix remodeling, pro-inflammation and resolution. (3) Results: The addition of HA decreased matrix marker genes, downregulated the fibrosis marker α-SMA for a short time and slightly increased the matrix-remodeling gene MMP-2. Of the pro-inflammatory marker genes, only IL-6 was significantly upregulated. IL-6 has to be kept in check, although IL-6 is also needed for a proper initial inflammation and efficient resolution. (4) Conclusions: The observed effects in vitro support the intended anti-adhesion effect and therefore, the use of HMW HA is promising as a biodegradable implant for tendon repair.