IMP3 Immunohistochemical Expression Is Related with Progression and Metastases in Xenografted and Cutaneous Melanomas.

INTRODUCTION: Insulin-like growth factor-II messenger RNA-binding protein-3 (IMP3) over-expression is a predictor of tumor recurrence and metastases in some types of human melanoma. Our objective was to evaluate the immunohistochemical expression of IMP3 and other molecules related to tumor prognosis in melanoma-xeno-tumors undergoing treatment. We test the effect of radiotherapy (RT) and mesenchymal stromal cells (MSCs) treatment, analyzing the tumorigenic and metastatsizing capacity in a mice melanoma xenograft model. MATERIALS AND METHODS: We inoculated A375 and G361 human melanoma cell lines into NOD/SCID gamma mice (n = 64). We established a control group, a group treated with MSCs, a group treated with MSCs plus RT, and a group treated with RT. We assessed the immunohistochemical expression of IMP3, E-cadherin, N-cadherin, PARP1, HIF-1α, and the proliferation marker Ki-67. Additionally, we performed a retrospective study including 114 histological samples of patients diagnosed with malignant cutaneous superficial spreading melanoma (n = 104) and nodular melanoma (n = 10) with at least 5 years of follow-up. RESULTS: Most morphological and immunohistochemical features show statistically significant differences between the 2 cell lines. The A375 cell line induced the formation of metastases, while the G361 cell line provoked tumor formation but not metastases. All three treatments reduced the cell proliferation evaluated by the Ki-67 nuclear antigen (p = 0.000, one-way ANOVA test) and reduced the number of metastases (p = 0.004, one-way ANOVA test). In addition, the tumor volumes reduced in comparison with the control groups, 31.74% for RT + MSCs in the A357 tumor cell line, and 89.84% RT + MSCs in the G361 tumor cell line. We also found that IMP3 expression is associated with greater tumor aggressiveness and was significantly correlated with cell proliferation (measured by the expression of Ki-67), the number of metastases, and reduced expression of adhesion molecules. CONCLUSIONS: The combined treatment of RT and MSCs on xenografted melanomas reduces tumor size, metastases frequency, and the epithelial to mesenchymal transition/PARP1 metastatic phenotype. This treatment also reduces the expression of molecules related to cellular proliferation (Ki-67), molecules that facilitate the metastatic process (E-cadherin), and molecules related with prognosis (IMP3).

Radiographic evaluation of radial flexion osteotomy effect on static scapholunate instability: a preliminary cadaveric study.

INTRODUCTION: The optimal treatment of chronic scapholunate instability has yet to be established. Scapholunate ligament grafts are still far from being the ideal solution. We conducted an experimental study to evaluate whether flexion-opening wedge osteotomy of the distal radius improves misalignment and avoids rotatory subluxation of the scaphoid in a cadaveric model of static scapholunate dissociative instability. MATERIALS AND METHODS: Radiographic studies were performed on 15 cryopreserved specimens after recreating a model of scapholunate instability by division of the scapholunate interosseous ligament (SLIL) and secondary stabilizers, taking radiographs at baseline, after the instability model, and after distal radius osteotomy. Static and dynamic (under controlled tendon traction) anteroposterior and lateral views were obtained to measure the length (in mm) of the carpal scaphoid and scapholunate interval, scapholunate angle, radio-lunate angle, and palmar tilt of the distal joint surface of the radius and to measure the dorsal scaphoid translation by the concentric circles method. The Wilcoxon test was used for statistical comparisons. RESULTS: The scapholunate interval was significantly decreased after osteotomy in all static anteroposterior views and in all lateral views under tendon traction. Dorsal scaphoid translation was significantly reduced in static lateral view in extension and in dynamic lateral view under 5-pound flexor carpi radialis tendon tension controlled by a digital dynamometer. CONCLUSIONS: Flexion-addition osteotomy of the distal radius appears to improve carpal alignment parameters in a cadaveric model of static scapholunate instability, achieving similar values to those obtained before instability.

Density mapping of nerve endings in the skin of the palm and flexor retinaculum of the hand. Application to open carpal tunnel release.

In order to re-evaluate the safest area to incise skin and the flexor retinaculum (FR) when performing a carpal tunnel release (CTR), we carried out a mapping study of the nerve endings in the skin and FR on cadaver specimens, which, unlike previous studies for the first time, includes histomorphometry and image digital analysis. After dividing the skin and FR into 20 and 12 sections, respectively, we carried out a histomorphological analysis of nerve endings. The analysis was performed by two neutral observers on 4-µm histological sections stained with hematoxylin-eosin (H-E), and Klüver-Barrera with picrosirius red (KB + PR) methods. A semi-automatic image digital analysis was also used to estimate the percentage of area occupied per nerve. We observed a lower quantity of nerve endings in the skin of the palm of the hand in line with the ulnar aspect of the 4th finger. The ulnar aspect of the FR was the most densely innervated. However, there are no statistically significant differences between sections in the percentage of area occupied per nerve both in the skin and in the FR. We concluded that there is not a safe area to incise when performing carpal tunnel surgery, but taking into account the quantity of nerve endings present in skin and FR, we recommend an incision on the axis of the ulnar aspect of 4th finger when incising skin and on the middle third of the FR for CTR.

Expression of Musashi-1 Increases in Bone Healing.

Musashi-1 (MSI1) is an RNA-binding protein that regulates progenitor cells in adult and developing organisms to maintain self-renewal capacities. The role of musashi-1 in the bone healing environment and its relation with other osteogenic factors is unknown. In the current study, we analyze the expression of MSI1 in an experimental model of rat femoral bone fractures. We also analyze the relation between MSI1 expression and the expression of two osteogenic markers: periostin (POSTN) and runt-related transcription factor 2 (RUNX2). We use histological, immunohistochemical, and qPCR techniques to evaluate bone healing and the expression of MSI1, POSTN, and RUNX2 over time (4, 7, and 14 days). We compare our findings with non-fractured controls. We find that in bone calluses, the number of cells expressing MSI1 and RUNX2 increase over time and the intensity of POSTN expression decreases over time. Within bone calluses, we find the presence of MSI1 expression in mesenchymal stromal cells, osteoblasts, and osteocytes but not in hypertrophic chondrocytes. After 14 days, the expression of MSI1, POSTN, and RUNX2 was significantly correlated. Thus, we conclude that musashi-1 potentially serves in the osteogenic differentiation of mesenchymal stromal cells and bone healing. Therefore, further studies are needed to determine the possibility of musashi-1's role as a clinical biomarker of bone healing and therapeutic agent for bone regeneration.

Anatomic study of pedicled bipolar teres major transfer for irreparable posterosuperior rotator cuff tears.

BACKGROUND: Treatment of rotator cuff (RC) tears has not included bipolar muscle-tendon transfers to date. The objective of this study was to verify the feasibility of pedicled bipolar teres major (TM) transfer over and under the long head of the triceps brachii (LHT) and compare its versatility with monopolar transfer in a model of supraspinatus (SS) tears in cadavers. METHODS: In 6 shoulders of cryopreserved cadavers, we re-created complete SS tears, conducting monopolar and bipolar TM transfers over and under LHT. We compared the morphology of the SS and TM, defect coverage, angle between the transferred TM and major SS axis, and axillary nerve overlap with each technique. RESULTS: The TM and SS were morphologically similar. Defect coverage was significantly lower with monopolar transfer (12 ± 4 mm) than with bipolar transfer (39 ± 9 mm under the LHT, P = .003, and 38 ± 8 mm over the LHT, P = .004). The bipolar transfer course over the LHT was the nearest to the SS axis (39° ± 11°, P = .005). We found a greater axillary nerve overlap with bipolar transfer under the LHT (27 ± 8 mm) than with bipolar transfer over the LHT (1 ± 2 mm, P = .005) or monopolar transfer (0 mm, P < .001). CONCLUSION: Bipolar TM transfer is possible without neurovascular pedicle interference, obtaining greater RC defect coverage and the closest path to the SS axis when conducted over the LHT compared with monopolar or bipolar transfer under the LHT. Accordingly, it can be considered an alternative option for the treatment of posterosuperior RC defects.

Cortistatin inhibits migration and proliferation of human vascular smooth muscle cells and decreases neointimal formation on carotid artery ligation.

RATIONALE: Proliferation and migration of smooth muscle cells (SMCs) are key steps for the progression of atherosclerosis and restenosis. Cortistatin is a multifunctional neuropeptide belonging to the somatostatin family that exerts unique functions in the nervous and immune systems. Cortistatin is elevated in plasma of patients experiencing coronary heart disease and attenuates vascular calcification. OBJECTIVE: To investigate the occurrence of vascular cortistatin and its effects on the proliferation and migration of SMCs in vitro and in vivo and to delimitate the receptors and signal transduction pathways governing its actions. METHODS AND RESULTS: SMCs from mouse carotid and human aortic arteries and from human atherosclerotic plaques highly expressed cortistatin. Cortistatin expression positively correlated with the progression of arterial intima hyperplasia. Cortistatin inhibited platelet-derived growth factor-stimulated proliferation of human aortic SMCs via binding to somatostatin receptors (sst2 and sst5) and ghrelin receptor, induction of cAMP and p38-mitogen-activated protein kinase, and inhibition of Akt activity. Moreover, cortistatin impaired lamellipodia formation and migration of human aortic SMCs toward platelet-derived growth factor by inhibiting, in a ghrelin-receptor-dependent manner, Rac1 activation and cytosolic calcium increases. These effects on SMC proliferation and migration correlated with an inhibitory action of cortistatin on the neointimal formation in 2 models of carotid arterial ligation. Endogenous cortistatin seems to play a critical role in regulating SMC function because cortistatin-deficient mice developed higher neointimal hyperplasic lesions than wild-type mice. CONCLUSIONS: Cortistatin emerges as a natural endogenous regulator of SMCs under pathological conditions and an attractive candidate for the pharmacological management of vascular diseases that course with neointimal lesion formation.

Morphological evidences of Bio-Oss® colonization by CD44-positive cells.

OBJECTIVES: Our objectives were to examine vascular and cellular colonization in anorganic bovine bone (ABB) after 6 months of healing in human maxillary sinus augmentation grafts. MATERIAL AND METHODS: Fifty unilateral maxillary sinus augmentation procedures were performed on 50 consecutive patients. Bone cores were obtained through the implant receptor sites 6 months later and evaluated with morphological image analysis and immunohistochemical techniques. RESULTS: Image analysis revealed a mean of 35.44 ± 16% vital bone, 31.66 ± 15% non-mineralized tissue, and 32.72 ± 25% remnant ABB particles. In our patients, neovascularization in 46.3% of cases was demonstrated within ABB particles 6 months after sinus floor augmentation surgery. Neovascularization of ABB particles was inversely related to age, directly to osteoclast number per mm², and not influenced by habits or disease. CD44-positive cells colonization was found in 74% of cases. An important correlation was found regarding CD44 expression and number of vessel in ABB particles (r = 0.624 P < 0.001, Pearson). Osteopontin expression was detected on the interstitial boundary of bone with ABB particles and within the osteocyte lacunae and bone canaliculi and was relationship with presence of CD44-positive cells inside ABB particles (r = 0.388, P = 0.046, Pearson). CONCLUSION: In conclusion, images compatible with osteone colonized by osteocytes CD44 positive and neovascularization in ABB particles were observed after 6 months of graft maturation. These biologic events have not previously been morphologically and immunohistochemically documented.

Association between radioulnar impingement and salvage surgical procedures of the distal radioulnar joint: influence of confounding variables.

We conducted an ambispective cohort study to assess the association between symptomatic radioulnar impingement syndrome (SRUIS) and distal radioulnar joint (DRUJ) salvage surgery to examine the influence of confounders on the final effect. The outcome variable was the incidence of SRUIS and the exposure variable was the surgical procedure. Seventy-two patients with median age of 48 years (IQR 25-78) were examined using bivariate and logistic regression multivariate analyses, and confounders were analysed in 15 multivariate models. Overall, SRUIS occurred in 21 patients (29%). Bivariate analysis showed a significant association between SRUIS and type of surgical procedure, observed in 71% after Sauvé-Kapandji, 50% after Bowers and 15% after Darrach procedure. When adjusted for age, aetiology and previous surgery, the significant association disappeared. Confounding is an important factor when accounting for SRUIS after DRUJ salvage surgery. The risk of SRUIS did not depend on the procedure, but rather on patient's age, aetiology and previous surgery.Level of evidence: II.

Histological characterization of the human scapholunate ligament.

The scapholunate interosseous ligament (SLIL) plays a fundamental role in stabilizing the wrist bones, and its disruption is a frequent cause of wrist arthrosis and disfunction. Traditionally, this structure is considered to be a variety of fibrocartilaginous tissue and consists of three regions: dorsal, membranous and palmar. Despite its functional relevance, the exact composition of the human SLIL is not well understood. In the present work, we have analyzed the human SLIL and control tissues from the human hand using an array of histological, histochemical and immunohistochemical methods to characterize each region of this structure. Results reveal that the SLIL is heterogeneous, and each region can be subdivided in two zones that are histologically different to the other zones. Analysis of collagen and elastic fibers, and several proteoglycans, glycoproteins and glycosaminoglycans confirmed that the different regions can be subdivided in two zones that have their own structure and composition. In general, all parts of the SLIL resemble the histological structure of the control articular cartilage, especially the first part of the membranous region (zone M1). Cells showing a chondrocyte-like phenotype as determined by S100 were more abundant in M1, whereas the zone containing more CD73-positive stem cells was D2. These results confirm the heterogeneity of the human SLIL and could contribute to explain why certain zones of this structure are more prone to structural damage and why other zones have specific regeneration potential. RESEARCH HIGHLIGHTS: Application of an array of histological analysis methods allowed us to demonstrate that the human scapholunate ligament is heterogeneous and consists of at least six different regions sharing similarities with the human cartilage, ligament and other anatomical structures.

Anthropometric study of the scapula in a contemporary population from granada. Sex estimation and glenohumeral osteoarthritis prevalence.

Anthropometric studies of the scapula have been rare in Spanish populations, nevertheless they are of current interest in forensic anthropology for estimation of sex. Although the estimation of sex is usually carried out on the pelvis and skull, other measurements related to the scapula can be helpful when the skeletal remains are incomplete. Glenohumeral osteoarthritis development is influenced, among others, by the morphology of the scapula, which is one of the less studied aspects. We carried out a descriptive study of anthropometric parameters in a series of 157 scapulae (82 individuals) on bone remains dated to the 20th century from a population of Granada (Southern Spain). Seventy seven (49%) were right-side and 80 (51%) left-side; 72 (45.9%) were from males and 85 (54.1%) from females, and the mean age at death was 70.76±11.7 years. The objective was to develop a discrimination function for sex estimation based on anthropometric parameters of the scapula other than those considered to date, and to analyze the prevalence of glenohumeral osteoarthritis in relation to selected anthropometric parameters. A logistic regression model based on parameters of the upper-external segment of the scapula was done. The obtained formula: 1/1+e^ (- (-57.911 + 0.350*B + 0283*C + 0.249*b + 0.166*a +-0.100*ß) classifies male sex with 98.3% accuracy and female sex with 92.1%. Glenohumeral osteoarthritis was detected in 16.6% of individuals and was related to age (p<0.05), scapular length (p<0.05), glenoid width (p<0.05), glenopolar angle (p<0.05), and α angle (p<0.05) in bivariate analyses but showed no significant associations in multivariate analyses. This approach can be useful for anthropological-forensic identification when scapula remains are incomplete. Glenohumeral osteoarthritis is significantly associated with a smaller α angle.

Surgical Treatment in Post-Stroke Spastic Hands: A Systematic Review.

Background: For more than two decades, the surgical treatment of post-stroke spastic hands has been displaced by botulinum toxin therapy and is currently underutilized. Objectives: This article aimed to assess the potential of surgery for treating a post-stroke spastic upper extremity through a systematic review of the literature on surgical approaches that are adopted in different profiles of patients and on their outcomes and complications. Methods: Medline PubMed, Web of Science, SCOPUS, and Cochrane Library databases were searched for observational and experimental studies published in English up to November 2022. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluations (GRADE) system. Results: The search retrieved 501 abstracts, and 22 articles were finally selected. The GRADE-assessed quality of evidence was low or very low. The results of the reviewed studies suggest that surgery is a useful, safe, and enduring treatment for post-stroke spastic upper extremities, although most studied patients were candidates for hygienic improvements alone. Patients usually require an individualized combination of techniques. Over the past ten years, interest has grown in procedures that act on the peripheral nerve. Conclusions: Despite the lack of comparative studies on the effectiveness, safety, and cost of the treatments, botulinum toxin has displaced surgery for these patients. Studies to date have found surgery to be an effective and safe approach, but their weak design yields only poor-quality evidence, and clinical trials are warranted to compare these treatment options.

PARP inhibition attenuates histopathological lesion in ischemia/reperfusion renal mouse model after cold prolonged ischemia.

We test the hypothesis that PARP inhibition can decrease acute tubular necrosis (ATN) and other renal lesions related to prolonged cold ischemia/reperfusion (IR) in kidneys preserved at 4°C in University of Wisconsin (UW) solution. Material and Methods. We used 30 male Parp1(+/+) wild-type and 15 male Parp1(0/0) knockout C57BL/6 mice. Fifteen of these wild-type mice were pretreated with 3,4-dihydro-5-[4-(1-piperidinyl)butoxyl]-1(2H)-isoquinolinone (DPQ) at a concentration of 15 mg/kg body weight, used as PARP inhibitor. Subgroups of mice were established (A: IR 45 min/6 h; B: IR + 48 h in UW solution; and C: IR + 48 h in UW solution plus DPQ). We processed samples for morphological, immunohistochemical, ultrastructural, and western-blotting studies. Results. Prolonged cold ischemia time in UW solution increased PARP-1 expression and kidney injury. Preconditioning with PARP inhibitor DPQ plus DPQ supplementation in UW solution decreased PARP-1 nuclear expression in renal tubules and renal damage. Parp1(0/0) knockout mice were more resistant to IR-induced renal lesion. In conclusion, PARP inhibition attenuates ATN and other IR-related renal lesions in mouse kidneys under prolonged cold storage in UW solution. If confirmed, these data suggest that pharmacological manipulation of PARP activity may have salutary effects in cold-stored organs at transplantation.

Physico-chemical and biological characterization of a new bovine bone mineral matrix available for human usage.

BACKGROUND: Anorganic bovine bone has been deeply studied for bone regeneration in the oral cavity. Different manufacturing processes can modify the final composition of the biomaterial and the responses that induce. AIM: To evaluate the physico-chemical characteristics of a bovine bone mineral matrix and the clinical, radiographical, histological, and mRNA results after using it for maxillary sinus floor augmentation in humans. MATERIALS AND METHODS: First, the physical-chemical characteristics of the biomaterial were evaluated by X-ray powder diffraction, X-ray fluorescence, and electron microscopy. A frequently used biomaterial with the same animal origin was used as comparator. Then, a clinical study was designed for evaluating clinical, radiographical, histological, and mRNA outcomes. Patients in need of two-stage maxillary sinus floor augmentation were included in the study. Six months after the grafting procedure, a bone biopsy was collected for evaluation. RESULTS: In terms of physico-chemical characteristics, no differences were found between both biomaterials. Clinically, 10 patients were included in the study. After 6 months, clinical and radiographical data showed adequate outcomes for allowing implant placement. Histological, immunohistochemical and mRNA analyses showed that the biomaterial in use provides biological support to induce responses similar to those of other commonly used biomaterials. CONCLUSION: Bovine bone mineral matrix (Creos™ Xenogain) used as a single material for maxillary sinus floor augmentation shows adequate biological, clinical, and radiological outcomes. In fact, the results from this study are similar to those reported in the literature for another bovine bone-derived biomaterial with whom it shares composition and micro- and nanoscale characteristics.

Complications associated with implant migration into the maxillary sinus cavity.

BACKGROUND: Migration of dental implants into the maxillary sinus is an uncommon, but increasingly reported complication. Implant migration may result from initial lack of primary stability, intrasinusal and nasal pressure changes, autoimmune reaction to the implant or incorrect distribution of occlusal forces. This retrospective study aims at analyzing the factors that may influence implant migration into the maxillary sinus cavity. MATERIAL AND METHODS: Fourteen patients presenting a total 15 implants that migrated into the maxillary sinus were recruited. Diagnosis of this complication was based on imaging techniques, such as cone beam computerized tomography scan and panoramic radiography. Clinical data were recorded in all cases and processed for statistical analysis. RESULTS: ABH was below 6 mm in the majority of cases. However, almost 50% of the patients did not receive any site preparation treatment prior to implant insertion. Five patients (33.3%) were treated by osteotome techniques, but only one of them had bone grafting. Therefore, 73.3% of sites did not receive any biomaterial to increase available bone height. The most common complication-associated factors found on this study were related to implant design (cylindrical), implant dimension (diameter), implant restoration/rehabilitation method (partial removable denture), site-specific anatomy (initial residual bone height between 5 and 6.9 mm), demographics (age), and biomaterials. CONCLUSION: Patient selection and proper treatment planning, as well as the application of the appropriate sinus augmentation technique, are critical aspects that should be controlled to minimize the risk of implant migration into the maxillary sinus cavity.

Extensor Pollicis Brevis Transosseous Tenodesis Technique for Treatment of Acquired Metacarpophalangeal Hyperextension Deformity of the Thumb: A Preliminary Report.

SUMMARY: Hyperextension deformity of the metacarpophalangeal joint of the thumb causes pain and loss of function. Although many treatments have been proposed, none of them are universally accepted as ideal. The authors report a study of 12 symptomatic hyperextension deformities of the thumb metacarpophalangeal joint in 10 patients who underwent surgical correction. The purpose of this study was to describe a new technique of tenodesis of the thumb metacarpophalangeal joint using the extensor pollicis brevis tendon. The technique consists of extensor pollicis brevis tenotomy at the wrist and tendon transfer through two bone tunnels to the palmar aspect of the metacarpophalangeal joint before metacarpal fixation with a flexor tenodesis effect. Correction of hyperextension and range of motion were assessed. Functional changes were evaluated by Quick Disabilities of the Arm, Shoulder, and Hand score, pain visual analogue scale, Kapandji opposition scheme, and pinch strength. The Wilcoxon test was used for statistical analysis. Mean preoperative and postoperative metacarpophalangeal joint hyperextension deformities were +50.83 ± 5.57 degrees and -17.91 ± 7.82 degrees, respectively. Thumb opposition improved by one point on Kapandji's scheme. Mean perceived pain decreased from 7.66 to 1.16. On average, the Quick Disabilities of the Arm, Shoulder, and Hand score was reduced by 34.4 points and pinch strength increased by 50.42 percent. The authors found that extensor pollicis brevis transosseous tenodesis is a safe and minimally invasive method for successfully correcting the functionality and cosmetic appearance of metacarpophalangeal joint hyperextension deformities in posttraumatic and trapeziometacarpal osteoarthritis cases. The patients retained functional active flexion, even in deformities greater than 40 degrees. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Dental implant migration in grafted maxillary sinus.

BACKGROUND: Migration of oral implants through a previously consolidated graft is an extremely rare event. We reported 2 cases of migration at least 6 months postimplantation in sinus grafted in 2 stages, consequently over 6-month graft maturation period. CASE DESCRIPTION: Sinus elevations and implants placement in 2 patients were performed. Clinical and radiographic follow-up after the prosthetic rehabilitation showed displacement of 1 implant in each patient through the histopathologically verified stable grafts. CLINICAL IMPLICATIONS: Implants migration through composite graft after maxillary sinus elevation was reported. Reasons for this to occur might be due to the following: fail to achieve implant primary stability, Schneiderian membrane perforation, or graft resorption due to increased osteoclastic activity.

Eight-year analysis of bullfighting injuries in Spain, Portugal and southern France.

Improving knowledge on the epidemiology and analysing the prognostic factors of severity for injuries caused by fighting bulls in Spain, Portugal and southern France. Observational retrospective study including 1239 patients with a reported history of bull horn injuries between January 2012 and November 2019 in Spain, Portugal or southern France. A multiple logistic regression test was used to analyse the prognostic factors of severity and mortality rate of these lesions. The mean accident rate was 9.13% and the mortality rate was 0.48%. The most frequent mechanism of trauma was goring, and the commonest locations of the lesions were thigh and groin. Vascular lesion was found in 20% of thigh/groin gorings. Prognostic factors of severity were vascular lesion, head trauma, fracture, goring injuries and age of the animal. The most reliable prognostic factors of mortality were vascular lesion and goring in the back. Lesions caused by fighting bulls are common in the bullfighting events held in Spain, Portugal and southern France. Although the mortality rate is low, there is a higher morbidity rate, which is conditioned by vascular lesion. All medical teams should include a surgeon experienced in vascular surgery and an anaesthesiologist.

Biomechanical Finite Element Method Model of the Proximal Carpal Row and Experimental Validation.

The Finite Element Method (FEM) models are valuable tools to create an idea of the behavior of any structure. The complexity of the joints, materials, attachment areas, and boundary conditions is an open issue in biomechanics that needs to be addressed. Scapholunate instability is the leading cause of wrist pain and disability among patients of all ages. It is needed a better understanding of pathomechanics to develop new effective treatments. Previous models have emulated joints like the ankle or the knee but there are few about the wrist joint. The elaboration of realistic computational models of the carpus can give critical information to biomedical research and surgery to develop new surgical reconstructions. Hence, a 3D model of the proximal carpal row has been created through DICOM images, making a reduced wrist model. The materials, contacts, and ligaments definition were made via open-source software to extract results and carry on a reference comparison. Thus, considering the limitations that a reduced model could carry on (unbalanced forces and torques), the stresses that result in the scapholunate interosseous ligament (SLIL) lead us to a bones relative displacement, which support the kinematics hypothesis in the literature as the distal carpal row moves as a rigid solid with the capitate bone. Also, experimental testing is performed, successfully validating the linear strength values of the scapholunate ligament from the literature.

The Neuropeptide Cortistatin Alleviates Neuropathic Pain in Experimental Models of Peripheral Nerve Injury.

Neuropathic pain is one of the most severe forms of chronic pain caused by the direct injury of the somatosensory system. The current drugs for treating neuropathies have limited efficacies or show important side effects, and the development of analgesics with novel modes of action is critical. The identification of endogenous anti-nociceptive factors has emerged as an attractive strategy for designing new pharmacological approaches to treat neuropathic pain. Cortistatin is a neuropeptide with potent anti-inflammatory activity, recently identified as a natural analgesic peptide in several models of pain evoked by inflammatory conditions. Here, we investigated the potential analgesic effect of cortistatin in neuropathic pain using a variety of experimental models of peripheral nerve injury caused by chronic constriction or partial transection of the sciatic nerve or by diabetic neuropathy. We found that the peripheral and central injection of cortistatin ameliorated hyperalgesia and allodynia, two of the dominant clinical manifestations of chronic neuropathic pain. Cortistatin-induced analgesia was multitargeted, as it regulated the nerve damage-induced hypersensitization of primary nociceptors, inhibited neuroinflammatory responses, and enhanced the production of neurotrophic factors both at the peripheral and central levels. We also demonstrated the neuroregenerative/protective capacity of cortistatin in a model of severe peripheral nerve transection. Interestingly, the nociceptive system responded to nerve injury by secreting cortistatin, and a deficiency in cortistatin exacerbated the neuropathic pain responses and peripheral nerve dysfunction. Therefore, cortistatin-based therapies emerge as attractive alternatives for treating chronic neuropathic pain of different etiologies.

Modification of intra-carpal tunnel pressure after Z-lengthening of the transverse carpal ligament.

Background Flexor retinaculum reconstruction techniques or simply Flexor Retinaculum Z-lengthening have been proposed to preserve Flexor Retinaculum continuity after carpal tunnel release. Their effectiveness is based solely on symptom relief. There has been no analysis of the effects on intra-carpal tunnel pressure of Flexor Retinaculum-lengthening techniques. Objective was to compare intra-carpal tunnel pressure outcomes between complete division and Z-lengthening of the Retinaculum in a cadaveric model of carpal tunnel release. Methods Experimental study of carpal tunnel pressure after surgical Flexor Retinaculum modification in 10 fresh-frozen forearm and hand cadaveric specimens. The Kyphon™ Balloon Kyphoplasty system was used to measure the pressure before and after infusing 1, 2, 3, 4 and 5 ml of saline solution when untreated (Flexor Retinaculum continuity stage I), when Z-lengthened (Flexor Retinaculum continuity stage II), and after complete Flexor Retinaculum division (Flexor Retinaculum continuity stage III). Finding Intra-carpal tunnel pressure increased with larger volume of infused saline solution, although mean pressures were lower after Z lengthening or complete division of the Retinaculum than at baseline. Analysis of linear regression coefficients indicated significant differences as a function of FR continuity stage (F(2,18) = 18.38, p < 0.001), while the Bonferroni test revealed significant differences in slopes between stages I and III (p = 0.003), between stages I and II (p < 0.02), but not between stages II and III (p > 0.05). Interpretation The effectiveness of carpal tunnel release and the reduction in intra-carpal tunnel pressures obtained by Z-lengthening of the FR were similar to those observed after its complete division, while preserving FR continuity.