Vascularization of the menisci: a descriptive study of the peri-meniscal archs.

PURPOSE: The meniscal vascularization remains poorly documented, particularly its origin. The aim of this cadaveric study was to describe the origin of the arterial vascularization of the menisci. METHODS: This is an anatomical study on human specimens. Twenty knees were used. The average age of the subjects was 82.7 years old (56-97). Ten knees were injected with latex-neoprene and ten knees were injected with colored gelatin mixed with India ink. The same protocol for dissection was used in all cases. RESULTS: The meniscal vascularization is provided by the genicular arteries of the knee originating from the popliteal artery. The superior medial, superior lateral, inferior medial, inferior lateral, and middle genicular arteries had constant pathways. A second middle genicular artery was found in 55% of cases. The inferior lateral genicular artery ran alongside the meniscal's periphery. The inferior medial genicular artery followed the proximal tibial metaphysis. In all dissections, a previously undocumented small artery originated from under the middle genicular arteries. This artery remained extracapsular and followed the medial meniscal periphery. This artery has been named the "medial capsulo-meniscal artery". The genicular arteries formed an extensive peri-articular anastomotic vascularization for the menisci and thus referred to the "peri-meniscal arterial archs". The lateral peri-meniscal arch was predominantly supplied by the inferior lateral genicular artery, while the medial peri-meniscal arch was mainly supplied by the medial capsulo-meniscal artery. CONCLUSION: The peri-meniscal arterial archs are a vascular complex formed by the genicular arteries of the knee and an artery not previously described: the "capsulo-meniscal artery". These archs have a constant presence but their formation and distribution is different between the medial and lateral menisci.

Human MuStem cells are competent to fuse with nonhuman primate myofibers in a clinically relevant transplantation context: A proof-of-concept study.

We previously reported that human muscle-derived stem cells (hMuStem cells) contribute to tissue repair after local administration into injured skeletal muscle or infarcted heart in immunodeficient rodent models. However, extrapolation of these findings to a clinical context is problematic owing to the considerable differences often seen between in vivo findings in humans versus rodents. Therefore, we investigated whether the muscle regenerative behavior of hMuStem cells is maintained in a clinically relevant transplantation context. Human MuStem cells were intramuscularly administered by high-density microinjection matrices into nonhuman primates receiving tacrolimus-based immunosuppression thereby reproducing the protocol that has so far produced the best results in clinical trials of cell therapy in myopathies. Four and 9 weeks after administration, histological analysis of cell injection sites revealed large numbers of hMuStem cell-derived nuclei in all cases. Most graft-derived nuclei were distributed in small myofiber groups in which no signs of a specific immune response were observed. Importantly, hMuStem cells contributed to simian tissue repair by fusing mainly with host myofibers, demonstrating their capacity for myofiber regeneration in this model. Together, these findings obtained in a valid preclinical model provide new insights supporting the potential of hMuStem cells in future cell therapies for muscle diseases.

Bilateral Obturator Osteotomy: A Novel Osteotomy for Bladder Exstrophy Closure.

BACKGROUND: Abdominal and pelvic closure remains a challenge during bladder exstrophy initial repair. We aimed to report on the feasibility and results of a novel technique of bilateral obturator osteotomy. METHODS: Retrospective study of prospective collected data of children who underwent single-stage delayed bladder exstrophy closure combined with RSTM (Radical Soft Tissue Mobilization) for BEEC (Bladder Exstrophy Epispadias Complex) by the same team at different institutions between December 2017 and May 2021. When pubic approximation was not feasible at the end of the procedure, bilateral obturator osteotomy was performed through the same approach, consisting in bilateral divisions of the ilio-pubic rami, ischio-pubic rami, obturator membrane, and detachment of the internal obturator muscle. Pubic bone fragments were approximated together on the midline. Immobilization in a thermoformed posterior splint was indicated for 3 weeks. The main outcome criterion was the bladder dehiscence rate at 6 months, assessed by physical inspection. Secondary outcome criteria included neurovascular obturator pedicle injury, analyzed during orthopedic physical examination, wound or bone infections, gait acquisition, reported by parents and evaluated during medical examination, and vascular penile impairment, judged by penile and glans coloration. RESULTS: 17 children (11 males, 6 females) were included, at a median age of 2 months [1-33]; and representing 29% (17/58) of the children with bladder exstrophy who underwent the same surgical approach during the time of study. There was no postoperative bladder dehiscence with a median follow-up of 34 months [6-47]. No complication was observed. Pelvic X-rays showed bilateral normal ossification process. Neither gait abnormality, nor clinical indication of obturator nerve deficiency was observed during follow-up. CONCLUSION: When pubic bones approximation is not possible, bilateral obturator osteotomy is a useful adjunct in bladder exstrophy closure, feasible by the pediatric urologist through the same approach, and not requiring external fixator. LEVEL OF EVIDENCE: IV.

Composition of encephalic arteries and origin of the basilar artery are different between vertebrates.

Intracranial arterial anatomy is lacking for most mammalian and non-mammalian model species, especially concerning the origin of the basilar artery (BA). Enhancing the knowledge of this anatomy can improve animal models and help understanding anatomical variations in humans. We have studied encephalic arteries in three different species of birds and eight different species of mammals using formalin-fixed brains injected with arterial red latex. Our results and literature analysis indicate that, for all vertebrates, the internal carotid artery (ICA) supplies the brain and divides into two branches: a cranial and a caudal branch. The difference between vertebrates lies in the caudal branch of the ICA. For non-mammalian, the caudal branch is the origin of the BA, and the vertebral artery (VA) is not involved in brain supply. For mammals, the VA supplies encephalic arteries in two different ways. In the first type of organization, mostly found in ungulates, the carotid rete mirabile supplies the encephalic arteries, the caudal branch is the origin of the BA, and the VA is indirectly involved in carotid rete mirabile blood supply. The second type of encephalic artery organization for mammals is the same as in humans. The caudal branch of the ICA serves as the posterior communicating artery, and the BA originates from both VAs. We believe that knowledge of comparative anatomy of encephalic arteries contributes to a better understanding of animal models applicable to surgical or radiological techniques. It improves the understanding of rare encephalic variations that may be present in humans.

How Does Customized Cutting Guide Design Affect Accuracy and Ergonomics in Pelvic Tumor Resection? A Study in Cadavers.

BACKGROUND: Customized cutting guides are technical aids that make primary pelvic bone tumor resection safer and more reliable. Although the effectiveness of such devices appears to be widely accepted, their conception and design remain varied. Two main designs have been reported: the heavier block-type customized cutting guides and the lighter patch-type customized cutting guides. As recent tools, there must be more evidence regarding the impact of design on their accuracy and ergonomics. Thus, an evaluation of their respective performances appears warranted. QUESTIONS/PURPOSES: In a cadaver model, we assessed whether (1) a thinner, patch-type customized cutting guide design results in resections that are closer to the planned resections than the heavier block-type customized cutting guides, and (2) the patch-type customized cutting guide design is more ergonomic than the block-type customized cutting guide with improved usability in surgery (in terms of bulkiness, ease of placement, primary and secondary stability, and stability during cutting). METHODS: We conducted an experimental study involving five fresh whole-body anatomic specimens (three women and two men with a median age of 79 years and median weight of 66 kg) by simulating six virtual tumors in three areas according to the Enneking classification (Zones I: iliac wing, II: periacetabular area, and I and IV: sacroiliac joint area). We compared the impact of the customized cutting guide's design on performance in terms of the resection margin accuracy using CT scan analysis (deviation from the planned margin at the closest point and the maximum deviation from the planned margin) and the intraoperative ergonomic score under conditions simulating those of an oncologic resection of a bone tumor (with a range of 0 to 100, with 100 being best). RESULTS: The patch customized cutting guides performed slightly better than the block customized cutting guides regarding deviation from the planned margin at the closest point, with median values of 1 mm versus 2 mm (difference of medians 1 mm; p = 0.02) and maximum deviation from the planned margin of 3 versus 4 mm (difference of medians 1 mm; p = 0.002). In addition, the patch design was perceived to be slightly more ergonomic than the block design, with a 92% median score versus 84% for the block design (difference of medians 8%; p = 0.03). CONCLUSION: We observed an equivalence in performance regarding accuracy and ergonomics, with slight advantages for patch customized cutting guides, especially in complex zones (Zone I and IV). Owing to a small cohort in a cadaver study, these results need independent replication. CLINICAL RELEVANCE: The patch-type customized cutting guide with thinner contact spots to the bone in specific areas and less soft tissue dissection might offer an advantage over a larger block design for achieving negative oncologic bony margins, but it does not address issues of soft tissue margins.

Osteoarthritic chondrocytes undergo a glycolysis-related metabolic switch upon exposure to IL-1b or TNF.

BACKGROUND: Osteoarthritis is an age-related disease that currently faces a lack of symptomatic treatment. Inflammation, which is mainly sustained by pro-inflammatory cytokines such as IL-1b, TNF, and IL-6, plays an important role in osteoarthritis progression. In this context, pro-inflammatory cytokines are widely used to mimic the inflammatory component of osteoarthritis in vitro. However, the therapeutic failures of clinical trials evaluating anti-cytokines drugs highlight the lack of overall understanding of the effects of these cytokines on chondrocytes. METHODS: Here, we generated a comprehensive transcriptomic and proteomic dataset of osteoarthritic chondrocytes treated with these cytokines to describe their pro-inflammatory signature and compare it to the transcriptome of non-osteoarthritic chondrocytes. Then, the dysregulations highlighted at the molecular level were functionally confirmed by real-time cellular metabolic assays. RESULTS: We identified dysregulation of metabolic-related genes in osteoarthritic chondrocytes but not in non-osteoarthritic chondrocytes. A metabolic shift, toward increased glycolysis at the expense of mitochondrial respiration, was specifically confirmed in osteoarthritic chondrocytes treated with IL-1b or TNF. CONCLUSION: These data show a strong and specific association between inflammation and metabolism in osteoarthritic chondrocytes, which was not found in non-osteoarthritic chondrocytes. This indicates that the link between inflammation and metabolic dysregulation may be exacerbated during chondrocyte damage in osteoarthritis. Video Abstract.

Comparison of MRI T1, T2, and T2* mapping with histology for assessment of intervertebral disc degeneration in an ovine model.

An easy, reliable, and time-efficient standardized approach for assessing lumbar intervertebral disc (IVD) degeneration with relaxation times measurements in pre-clinical and clinical studies is lacking. This prospective study aims to determine the most appropriate method for lumbar IVD degeneration (IDD) assessment in sheep by comparing three quantitative MRI sequences (variable-flip-angle T1 mapping, and multi-echo T2 and T2* mapping), correlating them with Pfirrmann grading and histology. Strong intra- and interrater agreements were found for Nucleus pulposus (NP) regions-of-interest (ROI). T1, T2, and T2* mapping correlated with Pfirrmann grading and histological scoring (p < 0.05) except for the most ventral rectangular ROI on T2 maps. Correlations were excellent for all of the T1 ROIs and the T2* NP ROIs. Highly significant differences in T1 values were found between all Pfirrmann grades except between grades I/II and between grades III/IV. Significant differences were identified in the T2 and the T2* values between all grades except between grades I/III. T1, T2, and T2* relaxation times measurements of the NP are an accurate and time-efficient tool to assess lumbar IDD in sheep. Variable-flip-angle T1 mapping may be further considered as a valuable method to investigate IDD and to assess the efficacy of regenerative treatments in longitudinal studies.

Arthroscopic suture-fixation of anterior tibial intercondylar eminence fractures by retensioning of the ACL and hollowing of the tibial footprint: Objective and subjective clinical results in a paediatric population.

INTRODUCTION: Anterior tibial intercondylar eminence fractures (ATIEF) of the knee are rare in children. They are associated with prefracture intraligamental distention of the anterior cruciate ligament (ACL). OBJECTIVE: The objective of this study was to evaluate the subjective and objective clinical results of an arthroscopic surgical technique by suture-fixation of the fracture and tensioning of the ACL through hollowing of the tibial footprint. HYPOTHESIS: Suture-tensioning of ATIEF arthroscopically helps to achieve treatment objectives by leaving the knee joint free of any hardware. MATERIALS AND METHODS: This single-operator monocentric retrospective study involved twenty children operated on over a period of 2-years and 10 months, from March 2013, and with a minimum of one-year follow-up. Surgery was indicated for Stage II to IV fractures according to the Meyers and McKeever classification. Type I fractures were excluded. Seventeen out of 20 patients were reviewed. The median age was 12 years at the time of surgery and the mean follow-up was 28 months. The fractures were 5 of stage II, 9 of III and 3 of IV. The scores of Lysholm, objective and subjective IKDC were collected. Residual objective laxity was measured using the GNRB arthrometer at 150N. A standard X-ray evaluation permitted detection of possible growth disorders. RESULTS: At 28 months of mean follow-up, the mean scores of Lysholm and subjective IKDC were 99 (95; 100) and 97 (92; 100), respectively. As for the objective IKDC, 14 knees were rated A and 3 were rated B. The mean differential residual laxity via GNRB was 0.94mm (0; 2.4). No radiological growth disorder was observed at the last follow-up. CONCLUSION: The ACL suture-tensioning technique is simple and reliable. It also preserves the joint of the adult to remain free of any residual hardware. LEVEL OF EVIDENCE: IV; retrospective cohort study.

Human MuStem cells repress T-cell proliferation and cytotoxicity through both paracrine and contact-dependent pathways.

BACKGROUND: Muscular dystrophies (MDs) are inherited diseases in which a dysregulation of the immune response exacerbates disease severity and are characterized by infiltration of various immune cell types leading to muscle inflammation, fiber necrosis and fibrosis. Immunosuppressive properties have been attributed to mesenchymal stem cells (MSCs) that regulate the phenotype and function of different immune cells. However, such properties were poorly considered until now for adult stem cells with myogenic potential and advanced as possible therapeutic candidates for MDs. In the present study, we investigated the immunoregulatory potential of human MuStem (hMuStem) cells, for which we previously demonstrated that they can survive in injured muscle and robustly counteract adverse tissue remodeling. METHODS: The impact of hMuStem cells or their secretome on the proliferative and phenotypic properties of T-cells was explored by co-culture experiments with either peripheral blood mononucleated cells or CD3-sorted T-cells. A comparative study was produced with the bone marrow (BM)-MSCs. The expression profile of immune cell-related markers on hMuStem cells was determined by flow cytometry while their secretory profile was examined by ELISA assays. Finally, the paracrine and cell contact-dependent effects of hMuStem cells on the T-cell-mediated cytotoxic response were analyzed through IFN-γ expression and lysis activity. RESULTS: Here, we show that hMuStem cells have an immunosuppressive phenotype and can inhibit the proliferation and the cytotoxic response of T-cells as well as promote the generation of regulatory T-cells through direct contact and via soluble factors. These effects are associated, in part, with the production of mediators including heme-oxygenase-1, leukemia inhibitory factor and intracellular cell adhesion molecule-1, all of which are produced at significantly higher levels by hMuStem cells than BM-MSCs. While the production of prostaglandin E2 is involved in the suppression of T-cell proliferation by both hMuStem cells and BM-MSCs, the participation of inducible nitric oxide synthase activity appears to be specific to hMuStem cell-mediated one. CONCLUSIONS: Together, our findings demonstrate that hMuStem cells are potent immunoregulatory cells. Combined with their myogenic potential, the attribution of these properties reinforces the positioning of hMuStem cells as candidate therapeutic agents for the treatment of MDs.

A Short-Course Antibiotic Prophylaxis Is Associated with Limited Antibiotic Resistance Emergence in Post-Operative Infection of Pelvic Primary Bone Tumor Resection.

Resections of primary pelvic bone tumors are frequently complicated by surgical site infections (SSIs), thereby impairing the functional prognosis of patients, especially in case of implant removal. Although prophylactic antibiotics play an essential role in preventing SSIs, there are presently no recommendations that support their appropriate use. This study aimed to assess the impact of a 24 h prophylactic protocol on the bacterial ecology, the resistance pattern, and the SSI healing rate. We hypothesized that this protocol not only limits the emergence of resistance but also results in a good cure rate with implant retention in case of SSI. A retrospective study was performed that included all patients with an SSI following a pelvic bone tumoral resection between 2005 and 2017 who received a 24 h antibiotic prophylaxis protocol. Twenty-nine patients with an SSI were included. We observed a 75.9% rate of polymicrobial infection, with a high prevalence of digestive flora microorganisms and a majority of wild-type phenotypes. We confirmed that there was no significant emergence of resistant flora. After first-line debridement, antibiotics (DA) if any implant was used, or debridement, antibiotics, and implant retention (DAIR) whenever possible, we obtained a 79.3% cure rate, with implant removal in 20% of cases. The absence of an implant was significantly associated with SSI healing. Early infection management and low resistance profiles may also have a positive effect, but this needs to be confirmed in a larger cohort. In light of this, the use of a 24 h prophylactic protocol in primary pelvic bone tumor resections is associated with a favorable infection cure rate and implant retention in case of SSI, and minimal selection of resistant microorganisms.

Posterior cruciate ligament: Anatomy, femoral insertion and relationships with the anterior menisco-femoral ligament in 23 cadaver knees.

BACKGROUND: Abundant anatomic descriptions exist of the posterior cruciate ligament (PCL) and menisco-femoral ligaments (MFLs). There is broad agreement that the PCL is composed of two bundles and inserts on the femur near the distal cartilage. However, a different configuration with a single bundle and a complex femoral insertion has been reported. The main objective of our cadaver study was to determine the number of anatomical bundles forming the PCL. We also described the insertion of the PCL and its relationships with the anterior menisco-femoral ligament (AMFL). HYPOTHESIS: The PCL consists of a single ribbon-like bundle and inserts on the femur separately from the AMFL. MATERIAL AND METHODS: We used 23 knees of fresh unembalmed cadavers, which we dissected under a microsurgery loupe. Inclusion criteria for the knees were freedom from trauma and scars. No age limits were set. The features of the PCL were studied using the clock method. Measurements were taken using callipers with a precision of 0.01mm. RESULTS: No knees were excluded from the final analysis. Macroscopically, the PCL appeared as a single bundle forming a slender flat ribbon. With the knee flexed at 90°, the ligament footprint extended from 58min to 25min on the right and from 48min to 2min on the left. The femoral insertion of the AMFL started 2.07mm from the distal cartilage and masked the distal insertion of the PCL. After removal of the AMFL, the middle of the femoral insertion of the PCL started on average 5.99mm from the distal cartilaginous rim when the knee was flexed at 90°. DISCUSSION: Our study confirms descriptions of the PCL as a single bundle shaped as a flat ribbon. The presence of the AMFL gives the appearance of a double bundle and partially masks the femoral insertion of the PCL, which is located further back relative to the distal joint cartilage. LEVEL OF EVIDENCE IV: Experimental cadaver study.

The Common Femoral Artery Is a Fixed Arterial Segment.

BACKGROUND: The risk of stent fracture caused by the movements of the hip joint is one of the limitations of the endovascular treatment of the common femoral artery (CFA). The aim of this study was to describe and analyze the deformations of the iliofemoral axis during flexion and extension of the hip, and to evaluate the impact of stents implanted in the CFA on the deformations observed. MATERIALS AND METHODS: This monocentric descriptive study was carried out on the pelvis obtained from three fresh cadavers (two men aged 72 and 71 years, respectively, and one 94-year-old woman). Arteriography was carried out to appreciate the deformations of the external iliac and common femoral arteries, and to analyze the femoral junctions. A first arteriography was carried out on native arteries, and a second one was carried out after the implantation of a stent in the CFA (Zilver PTX, Cook Medical, Bloomington, IN, USA). In all the cases, anterior and lateral images were obtained, with the hip maintained in extension (0°) or flexion (45°, 90°). RESULTS: In a neutral position (extension), four points of deformation of the iliofemoral axis were identified in the frontal (A, B, C, and D) and sagittal (A', B', C', D') planes. These points were the vertices of the angles formed by the arterial deformation in the frontal and sagittal planes. These four points of deformation observed in the two planes appeared overlapping (A/A', B/B', C/C', and D/D') and were located on the external iliac artery, the origin of the CFA, the femoral bifurcation and the superficial femoral artery, respectively. In the frontal plane, all the angles closed during flexion, and the closure of the angle increased with the degree of flexion. In the sagittal plane, we observed that the angles with the A', C', and D' vertices closed during the flexion of the hip, and that the angle with the B' vertex opened during flexion. The higher was the degree of flexion, the more the angles were accentuated. The implantation of one stent in the CFA modified neither the localization of the points of deformation nor the modifications of angles previously observed on the frontal and the sagittal sections. CONCLUSIONS: As seen from the front and side, the CFA is a fixed segment during the movements of extension and flexion of the hip. The implantation of a stent does not modify this observation.

Collateral effects of targeting the nucleus pulposus via a transpedicular or transannular surgical route: a combined X-ray, MRI, and histological long-term descriptive study in sheep.

PURPOSE: In the context of regenerative medicine strategies, based in particular on the injection of regenerative cells, biological factors, or biomaterials into the nucleus pulposus (NP), two main routes are used: the transpedicular approach (TPA) and the transannular approach (TAA). The purpose of our study was to compare the long-term consequences of the TPA and the TAA on intervertebral disc (IVD) health through a longitudinal follow-up in an ovine model. METHODS: The TPA and the TAA were performed on 12 IVDs from 3 sheep. Six discs were left untreated and used as controls. The route and injection feasibility, as well as the IVD environment integrity, were assessed by MRI (T2-weighted signal intensity), micro-CT scan, and histological analyses (Boos' scoring). The sheep were assessed at 1, 3, and 7 months. RESULTS: Both the TPA and the TAA allowed access to the NP. They both induced NP degeneration, as evidenced by a decrease in the T2wsi and an increase in the Boos' scores. The TPA led to persistent end-plate defects and herniation of NP tissue (Schmorl's node-like) after 7 months as well as the presence of osseous fragments in the NP. CONCLUSIONS: The TPA induced more severe lesions in IVDs and vertebrae compared to the TAA. The lesions induced by the TPA are reason to consider whether or not this route is optimal for studying IVD regenerative medicine approaches.

[Musculoskeletal tumour surgery for adolescent and young-adult population: Collaboration between adult and pediatric surgeons is necessary]. / Collaboration pédiatre-adulte dans la chirurgie des tumeurs musculosquelettiques.

Orthopaedic surgery I has a key role on the medical pathway of adolescent and young-adult (AYA) patients with musculo-skeletal tumor from diagnosis, tumor resection, musculo-skeletal immediate or delayed reconstruction, to dealing with late complications and sequelae following reconstruction during childhood. Administrative authorizations, organization by health authorities as well as training courses are quite different for adult and pediatric surgery. However, surgery for musculo-skeletal tumors in AYA patients have neither adult nor pediatric specifities; resection-reconstruction rules and technics are the same for adult or pediatric patients, with nevertheless lower complication rate and more biologic reconstructions for the youngest, and more prosthetic reconstructions for the oldest. Late complications after bone and soft-tissue reconstructions in childhood and musculo-skeletal deformation after surgery and/or radiotherapy in childhood need the vision from "adult" orthopaedic teams for long and very long term success of the surgical project with a good knowledge of pediatric technics previously used. Thus, formal shared time and transition care are necessary between pediatric and adult surgical teams to prepare long-term follow-up of these childhood cancer survivors. Participation to the same specialized Multi-Disciplinary Board, scientific society gathering adult and pediatric surgeons, clinical trials with no age-limitation might help to erase barriers and to ease collaboration between adult and pediatric ortho-oncologic teams.

Dural arteries of the dorsoclival area.

OBJECTIVE: In the literature, there is a lack of complete description of dural arteries of the dorsoclival area with contradictory data. However, dorsoclival area is a site of tumors and vascular malformation or the skull base. That is why, the knowledge of dural arteries is very important. METHODS: Using a colored silicone mix preparation, fifteen sides of eight cranial bases were studied using 4-20× magnification of the surgical microscope. RESULTS: Dorsoclival area is supplying by three arterial complexes, internal carotid artery complex with always the dorsal meningeal artery for the superior two-third of the clivus, medial clival artery for the dorsum sellae, the external carotid artery complex with the hypoglossal and jugular branches of the ascending pharyngeal artery for the inferior one-third of the clivus, and the vertebral artery complex with the anterior meningeal artery for the most inferior part of the clivus and the anterior edge of the foramen magnum. Moreover, there are many anastomoses between those three arterial complexes at this area. CONCLUSION: Dural arterial supply of the dorsoclival area is very opulent. Its knowledge is important for surgical approaches and endovascular procedures.

RPL13 Variants Cause Spondyloepimetaphyseal Dysplasia with Severe Short Stature.

Variants in genes encoding ribosomal proteins have thus far been associated with Diamond-Blackfan anemia, a rare inherited bone marrow failure, and isolated congenital asplenia. Here, we report one de novo missense variant and three de novo splice variants in RPL13, which encodes ribosomal protein RPL13 (also called eL13), in four unrelated individuals with a rare bone dysplasia causing severe short stature. The three splice variants (c.477+1G>T, c.477+1G>A, and c.477+2 T>C) result in partial intron retention, which leads to an 18-amino acid insertion. In contrast to observations from Diamond-Blackfan anemia, we detected no evidence of significant pre-rRNA processing disturbance in cells derived from two affected individuals. Consistently, we showed that the insertion-containing protein is stably expressed and incorporated into 60S subunits similar to the wild-type protein. Erythroid proliferation in culture and ribosome profile on sucrose gradient are modified, suggesting a change in translation dynamics. We also provide evidence that RPL13 is present at high levels in chondrocytes and osteoblasts in mouse growth plates. Taken together, we show that the identified RPL13 variants cause a human ribosomopathy defined by a rare skeletal dysplasia, and we highlight the role of this ribosomal protein in bone development.

Implication of the inferolateral trunk of the cavernous internal CAROTID artery in cranial nerve blood supply: Anatomical study and review of the literature.

The inferolateral trunk (ILT) is one of the two more common branches of the cavernous internal carotid artery (ICA). Its knowledge is important for skull base surgery and endovascular interventional procedures. The ILT is described with superior, anterior and posterior branch, which is the complete form. These branches vascularize the oculomotor, trochlear, trigeminal and abducens nerves into the cavernous sinus and superior orbital fissure (SOF) courses, and through the foramens rotundum and ovale. We performed 21 injected embalmed cadaveric dissections combined with six specimen tomodensitometry. The ILT originates from the horizontal ICA segment and passes above the abducens nerve. Three branches arise from the ILT between the cavernous ICA and the ophthalmic and maxillary nerves initial courses. The main differences with the literature are the number of branches and their cranial nerves' blood supply. The more frequent ILT conformation is the incomplete form with anterior and posterior branch (13/21); the complete form is present in 5/13 sides (38%) and the ILT is in common with the meningohypophyseal trunk in 3/21 (14%) sides. The anterior branch always vascularizes the cranial nerves into the SOF course and most often the maxillary nerve through the foramen rotundum. The posterior branch always vascularizes the mandibular nerve through the foramen ovale course and sometimes the maxillary nerve. This study has demonstrated that there are anastomoses between these branches and arteries arising from the external carotid. This study explains why the sacrifice of a branch of the ILT does not implicate cranial nerve palsy.

Descriptive and dynamic study of the medial patellofemoral ligament (MPFL).

PURPOSE: The goal of this study was to evaluate the anatomy of the medial patellar retinaculum and the medial patellofemoral ligament (MPFL) to provide an anatomical validation of a pediatric reconstruction technique. METHODS: Fifteen knees were dissected to study the MPFL and its relationship with the medial patellar retinaculum and the femoral insertion of the medial collateral ligament (MCL). The distances between the insertions of the MPFL of eight knees, and the patellar insertion of the MPFL and the femoral insertion of the MCL of four knees, were measured during the flexion to evaluate the isometricity of the native and reconstructed MPFL. RESULTS: The medial patellar retinaculum includes four structures: the fascia, fibrous expansions of the vastus muscles, the MPFL and the medial patellomeniscal ligament. The femoral insertion of the MPFL was located just behind the femoral insertion of the MCL in 12 knees. During flexion, the distance between the insertion on the upper patella and the femoral insertion of the MPFL increased while the distance between the insertion on the lower patella and the femoral insertion of the MPFL decreased. The variation in the distances measured during the flexion was greater between the MPFL insertions (nsup = 6.5 mm, ninf = 6.5 mm) than between the patellar insertion of the MPFL and the femoral insertion of the MCL (n'sup = 2.5 mm, n'inf = 5.75 mm). CONCLUSION: The MPFL is not isometric. Even though the results were obtained from knees of elderly specimens, this study demonstrates reconstruction of the MPFL should take into account its anatomy and biomechanical role in the knee.

In vitro and in vivo evaluation of an electrospun-aligned microfibrous implant for Annulus fibrosus repair.

Annulus fibrosus (AF) impairment is associated with reherniation, discogenic pain, and disc degeneration after surgical partial discectomy. Due to a limited intrinsic healing capacity, defects in the AF persist over time and it is hence necessary to adopt an appropriate strategy to close and repair the damaged AF. In this study, a cell-free biodegradable scaffold made of polycaprolactone (PCL), electrospun, aligned microfibers exhibited high levels of cell colonization, alignment, and AF-like extracellular matrix deposition when evaluated in an explant culture model. The biomimetic multilayer fibrous scaffold was then assessed in an ovine model of AF impairment. After 4 weeks, no dislocation of the implants was detected, and only one sample out of six showed a partial delamination. Histological and immunohistochemical analyses revealed integration of the implant with the surrounding tissue as well as homogeneously aligned collagen fiber organization within each lamella compared to the disorganized and scarcer fibrous tissue in a randomly organized control fibrous scaffold. In conclusion, this biomimetic electrospun implant exhibited promising properties in terms of AF defect closure, with AF-like neotissue formation that fully integrated with the surrounding ovine tissue.

Skeletal Muscle Regenerative Potential of Human MuStem Cells following Transplantation into Injured Mice Muscle.

After intra-arterial delivery in the dystrophic dog, allogeneic muscle-derived stem cells, termed MuStem cells, contribute to long-term stabilization of the clinical status and preservation of the muscle regenerative process. However, it remains unknown whether the human counterpart could be identified, considering recent demonstrations of divergent features between species for several somatic stem cells. Here, we report that MuStem cells reside in human skeletal muscle and display a long-term ability to proliferate, allowing generation of a clinically relevant amount of cells. Cultured human MuStem (hMuStem) cells do not express hematopoietic, endothelial, or myo-endothelial cell markers and reproducibly correspond to a population of early myogenic-committed progenitors with a perivascular/mesenchymal phenotypic signature, revealing a blood vessel wall origin. Importantly, they exhibit both myogenesis in vitro and skeletal muscle regeneration after intramuscular delivery into immunodeficient host mice. Together, our findings provide new insights supporting the notion that hMuStem cells could represent an interesting therapeutic candidate for dystrophic patients.