Joint-sparing arthroscopic management of avascular necrosis of the capitate.

Avascular necrosis of the proximal pole of the capitate is an exceedingly rare pathology with few therapeutic solutions. The largest published series concerned a cohort of 6 cases over 10 years. The present case concerns our experience with avascular necrosis of the capitate in a 20-year-old woman. Due to her age and high functional demand, we opted for a minimally invasive solution using arthroscopy. We performed an X-shaped palmaris longus tendon interposition arthroplasty at the midcarpal joint between the capitate and the lunate. We here report 2 years' follow-up.

Applying the WALANT technique to surgical treatment of distal radius fractures.

The Wide-Awake Local Anesthesia No Tourniquet (WALANT) method is a recent anesthesia option for surgery of the upper limbs based on the injection of an anesthetic solution containing adrenaline at the surgical site, hence circumventing tourniquet use. In a prospective study, we compared the functional outcomes using this anesthesia technique with those of the regional anesthesia (RA) technique for the surgical care of distal radius fractures (DRF). From November 2019 to June 2020, a non-randomized, single-center study was conducted with a cohort of 41 patients suffering from a DRF and who received volar plate fixation at a university hospital center. Twenty-one patients had WALANT surgery and 20 had RA with installation of a tourniquet. Over a period of 7 months, the clinical and radiological outcomes as well as the QuickDASH functional score were evaluated. Recovery of wrist function return to work, and analgesic withdrawal for the WALANT group occurred earlier than for the RA group. No noticeable differences were found regarding surgery duration or radiographic results. Using WALANT, functional wrist recovery occurs earlier than with RA. In our study, earlier analgesic stoppage, a quicker return to work and resumption of activity were observed with WALANT. As such, it should become part of the therapeutic arsenal for surgical treatment of DRF.

Combined strategies following surgical drainage for perianal fistulizing Crohn's disease: failure rates and prognostic factors.

AIM: The medico-surgical strategy for the treatment of perianal fistulizing Crohn's disease (CD) following surgical drainage remains challenging and debated. Our aims were to describe the failure rate of therapeutic interventions after drainage of the fistula tract and determine the factors associated with failure to optimize medico-surgical strategies. METHOD: All consecutive patients with perianal fistulizing CD who underwent surgical drainage with at least a 12-week follow-up were included. Failure was defined as the occurrence of at least one of the following items: abscess recurrence, purulent discharge from the tract, visible external opening and further drainage procedure(s). RESULTS: One hundred and sixty-nine patients were included. The median follow-up was 4.0 years. The cumulative failure rates were 20%, 30% and 36% at 1, 3 and 5 years, respectively. The cumulative failure rates in patients who had sphincter-sparing surgeries or seton removal were significantly higher than in those who had a fistulotomy. Anterior fistula [hazard ratio (HR) = 2.52 (1.13-5.61), P = 0.024], supralevator extension [HR = 20.78 (3.38-127.80), P = 0.001] and the absence or discontinuation of immunosuppressants after anal drainage [HR = 3.74 (1.11-12.5), P = 0.032] were significantly associated with failure in the multivariate analysis model. CONCLUSION: Combined strategies for perianal fistulizing CD lead to a failure rate of 36% at 5 years. Where advisable, fistulotomy may be preferred because it has a lower rate of recurrence. The benefits of immunosuppressants require a dedicated prospective randomized trial.

Solitary rectal ulcer syndrome in 102 patients: Do different phenotypes make sense?

BACKGROUND: Little is known about the pathophysiological mechanisms of solitary rectal ulcer syndrome (SRUS). AIMS: We aim to identify the different phenotypes, taking into account complaints, anatomy and anorectal physiology. METHODS: Complaints, endoscopy results, and physiology data of patients with histologically proven SRUS were collected and analysed. The associated anorectal diseases were faecal incontinence and obstructed defecation. The clinical aspects of SRUS were compared, and factors associated with anorectal diseases were identified. RESULTS: Overall, 102 consecutive patients were included. The predominant lesion was a rectal ulcer (66%), and inflammation of the rectal wall was present in 42% of patients. Abnormal rectal capacities and/or rectal perception was observed in more than half. Nearly half (52%) of the patients met the criteria for obstructed defecation and they tended to more frequently have psychiatric disease (66.7% vs 33.3%; p=0.07). Patients with faecal incontinence (17%) reported more self-perception of anal procidentia (p=0.01) and were more likely to have inflammation of the rectal wall (p=0.02), high-grade internal rectal procidentia (p=0.06) and anal hypotonia (p=0.004); their maximum tolerable volume was lower (p=0.004). CONCLUSION: The characteristics of patients with SRUS suggest different phenotypes. This may be a way to develop a comprehensive treatment strategy.

Incidental anal 18fluorodeoxyglucose uptake: Should we further examine the patient?

BACKGROUND: There are no studies on incidental anal 18F-fluorodeoxyglucose (18FDG) uptake. AIM: To assess the rate and aetiologies of incidental anal 18FDG uptake and to evaluate the correlation between 18FDG positron-emission tomography/computed tomography (PET/CT) parameters and the diagnosis of an anorectal disease. METHODS: The data from patients with incidental anal 18FDG uptake were retrospectively analysed. Patients who underwent anorectal examinations were identified and compared to those who did not undergo examinations. Patients who were offered treatment were then identified and compared to those who did not receive treatment. RESULTS: Among the 43020 18FDG PET/CT scans performed, 197 18FDG PET/CT scans of 146 patients (0.45%) reported incidental anal uptake. Among the 134 patients included, 48 (35.8%) patients underwent anorectal examinations, and anorectal diseases were diagnosed in 33 (69.0%) of these patients and treated in 18/48 (37.5%) patients. Among the examined patients, those with a pathology requiring treatment had significantly smaller metabolic volumes (MV) 30 and MV41 values and higher maximal and mean standardized uptake value measurements than those who did not require treatment. CONCLUSION: Incidental anal 18FDG uptake is rare, but a reliable anorectal diagnosis is commonly obtained when an anorectal examination is performed. The diagnosis of an anorectal disease induces treatment in more than one-third of the patients. These data should encourage practitioners to explore incidental anal 18FDG uptake systematically.

Sphincter-sparing surgery for complex anal fistulas: radiofrequency thermocoagulation of the tract is of no help.

AIM: To compare the rate of failure of radiofrequency thermocoagulation for anal fistula with that of rectal advancement flap in a case-matched study. METHOD: Patients who underwent radiofrequency treatment were compared with age- and sex-matched patients with Crohn's disease (CD) who underwent a rectal flap procedure. Fistula features, general characteristics and the main clinical events were recorded in a prospective database. Failure was defined by at least one of following: abscess, purulent discharge, visible external opening or further drainage procedure. RESULTS: A total of 62 patients [median age 45 (range 36.8-57.5) years; 22 women, 40 men; 22 with CD] were analysed. The failure rate of radiofrequency treatment was higher than that of rectal flap treatment (74.2% vs 32.2%; P = 0.004). The cumulative probabilities of failure of the radiofrequency treatment were 53.8% (38.8-68.3), 71.8% (55.3-84.0) and 87.4% (70.6-95.3) at 3, 6 and 12 months, respectively. Three patients in the radiofrequency group required drainage for an abscess and one had severe thermal ulceration. The Cox proportional hazards regression model (surgical procedure, obesity, CD) showed rectal flap treatment [3.48 (1.60-8.07); P = 0.001] and CD [2.60 (1.16-6.41); P = 0.02] to be the main independent predictors of healing. CONCLUSION: Radiofrequency thermocoagulation is a less satisfactory sphincter-sparing treatment for the management of anal fistula than a rectal flap procedure.

Advancement flap procedure in Crohn and non-Crohn perineal fistulas: a simple surgical approach.

AIM: Rectal flap advancement is still a part of therapeutic management of anal fistulas. Data on the outcome of rectal flap advancement in patients with Crohn's disease (CD) is scarce. Our objective was to ascertain rates of failure of rectal flap advancement and to determine predictive factors for failure, with a special focus on CD METHOD: The patients' details, the characteristics of the fistula and the main clinical and therapeutic events were prospectively assessed among patients who underwent rectal flap advancement. All patients had a partial-thickness rectal flap advancement. Failure of primary rectal flap advancement was defined as the occurrence of at least one of the following: abscess, discharge, visible external opening, further drainage procedure. The rates of failure of rectal flap and the predictive factors of failure were assessed. RESULTS: Eighty-seven patients (34 patients with CD) were included. The median (interquartile range) follow-up was 13.3 (3.8-38.1) months. The cumulative failure rates were 15.9% (10.3-23.6), 23.0% (16.0-31.8), 31.6% (22.9-41.8) and 41.3% (30.5-53.0) at 3, 6, 12 and 24 months respectively. These data were comparable in Crohn's patients. Those with a supralevator fistula [hazard ratio 2.53 (1.01-7.71), P = 0.0476] and patients who had fewer than two fistula drainages before rectal flap [hazard ratio 3.19 (1.40-8.23), P = 0.005] were associated with higher rectal flap failure rates. In CD patients, the absence of biological therapy at referral was predictive of failure. CONCLUSION: Rectal flap advancement is a satisfactory option for the therapeutic management of anal fistula, including CD populations. Fistula drainage is needed before performing this surgical technique.

Poor outcomes of fusion with Trabecular Metal implants after failed total ankle replacement: Early results in 11 patients.

INTRODUCTION: One of the reasons for revision of total ankle replacement (TAR) implants is loosening due to subchondral cysts. Reconstruction and fusion of the ankle is often the first choice for revision procedures due to the large bone defects, which are typically filled with autograft and/or allograft. Filling the defect with a trabecular metal tantalum implant is a potential alternative given the biomechanical properties of this component. HYPOTHESIS: Using tantalum as a spacer provides primary stability and contributes to fusion of the ankle joint after removal of failed TAR implants. METHODS: Eleven patients underwent arthrodesis an average of 6.9 years after TAR. The mean height of the bone defect was 32mm. It was filled with a specially designed quadrangular implant (Trabecular Metal™, Zimmer/Biomet) combined with an iliac crest graft. Ten patients underwent tibio-talo-calcaneal (TTC) arthrodesis fixed with an angled retrograde nail and one patient underwent talocrural arthrodesis fixed with two plates (anterolateral and anteromedial). The clinical, functional (AOFAS and SF36 scores) and radiological (plain X-rays and CT scan) outcomes were determined. RESULTS: At a mean follow-up of 19.3 months, the mean total AOFAS score was 56 (21-78) and the mean SF36 score was 60.5 (19-84). One patient was lost to follow-up and four patients still had pain. The tantalum implant was integrated in six patients. Five patients achieved fusion of the subtalar joint and 8 achieved fusion of the talocrural joint. Three patients required surgical revision. DISCUSSION: Our hypothesis was not confirmed. The clinical outcomes after more than 1 year of follow-up are disappointing, as was the large number of nonunion cases and the lack of tantalum integration. These technical failures can be explained by insufficient construct stability and/or insufficient implant porosity. LEVEL OF EVIDENCE: IV (retrospective cohort study).

Anal ulcerations in Crohn's disease: Natural history in the era of biological therapy.

BACKGROUND: The natural history of anal ulcerations in Crohn's disease remains unknown. AIMS: To assess the long-term outcomes of anorectal ulcerations. METHODS: Data from consecutive patients with perineal Crohn's disease were prospectively recorded. The data of patients with anal ulceration were extracted. RESULTS: Anal ulcerations were observed in 154 of 282 patients (54.6%), and 77 cases involved cavitating ulcerations. The cumulative healing rates were 47%, 70% and 82% at 1, 2 and 3 years, respectively. Patients with a primary fistula phenotype had a shorter median time to healing of their anal ulceration (28 [13-83] weeks) than those with a stricture (81 [28-135] weeks) or those with isolated ulceration (74 [31-181] weeks) (p=0.004). Among patients with ulcerations but no fistula at referral (n=67), only 4 (6%) developed de novo abscesses and/or fistula during follow-up. There was no benefit associated with introducing or optimising biologics, nor with combining immunosuppressants and biologics. CONCLUSION: Anal ulceration in Crohn's disease usually requires a long time to achieve sustained healing. Determining the impact of biologics on healing rates will require dedicated randomised trials although it does not show a significant healing benefit in the present study.

Hemi-arthroplasty for distal radius fracture in the independent elderly.

INTRODUCTION: The authors report their experience with hemi-arthroplasty in irreparable fresh distal radius fracture in independent elderly patients as first-line treatment (12 fractures in 11 women; mean age, 74 years) or in second line after clinically disabling primary failure (4 fractures in 4 women; mean age, 78 years). RESULTS: In the 12 primary surgeries, at a mean 32 months' follow-up, there were no complications requiring implant ablation; mean pain score was 1/10, flexion-extension 62°, Lyon Wrist score 75%, and Patient-Related Wrist Evaluation (PRWE) 22 points. In 2 of the 4 secondary surgeries, at a mean 24 months' follow-up, there were no complications requiring implant ablation; mean pain score was 2.5/10, flexion-extension 62°, Lyon Wrist score 58%, and PRWE 50 points: i.e., slightly poorer results than in primary surgery. CONCLUSION: Salvage of complex fracture in independent elderly patients by hemi-arthroplasty, whether primary or secondary to failure, seems to be a considerable progress, to be confirmed in larger series.

Reasons for and functional results of repeated hip arthroscopy: A continuous prospective study of 17 revisions out of 295 primary hip arthroscopies at mean 28months' follow-up.

INTRODUCTION: The rate of iterative arthroscopy has been increasing over the last decade as the technique has grown. The results of and reasons for these revision procedures, however, are not exactly known. We therefore conducted a prospective study to shed light on: 1) functional results and patient satisfaction following repeated arthroscopy, and 2) the relevant indications. HYPOTHESIS: Functional scores and patient satisfaction increase following repeated arthroscopy. MATERIALS AND METHOD: A single-center continuous prospective study without control group included patients undergoing repeated hip arthroscopy between September 2010 and September 2014, with a mean 28months' follow-up (median, 23.3months; range, 12-62months). Preoperative and follow-up functional assessment used the modified Harris hip, WOMAC and Christensen (NHAS) questionnaires, and a satisfaction scale. On etiological analysis, repeated arthroscopy was indicated if a cause of recurrent or persistent pain accessible to arthroscopic treatment was identified. RESULTS: Seventeen patients were included out of 295 primary arthroscopies (5.7%): 9 male, 8 female; median age, 29.6years (range, 16-48years). Indications for primary arthroscopy comprised 13 cases of femoroacetabular impingement, 3 labrum lesions with instability, 1 chondromatosis and 1 case of osteoarthritis. Eleven of the 17 primary lesions showed persistence, including 9 of the 13 cases of femoroacetabular impingement. There were 3 failures in 17 repeated arthroscopies. All functional scores improved, with a gain of 7 points (P<0.06) on modified Harris hip score, 25 points (P<0.0006) on WOMAC score, and 27 points (P<0.001) on NHAS score. Ten of the 17 patients were satisfied or very satisfied with the repeated arthroscopy (59%). CONCLUSION: Although less good than on primary arthroscopy, functional results on repeated hip arthroscopy were satisfactory in the short term. The main reason for repeated arthroscopy was persistence of initial abnormality due to insufficient treatment.

TGF-ß1 differentially modulates the collagen VI α5 and α6 chains in human tendon cultures.

Collagen VI is a microfibrillar collagen with a potential regulatory role in tendon repair mechanism. We studied the expression of collagen VI α5 and α6 chains in normal human tendon fibroblast cultures, both under basal condition and in response to TGF-ß1, a potent regulator of tendon healing. Under basal condition, we found that the α5 chain was expressed, although to a lesser extent with respect to the α3 chain; in contrast, the α6 chain was absent. The treatment with TGFß1 induced an opposite effect on the expression of the α5 and α6 chains; in fact, while the α5 chain was dramatically reduced, the α6 chain was induced and released in the culture medium. These data indicate that collagen VI α5 and α6 chains are differentially involved in tendon matrix homeostasis. The α6 chain may represent a new potential biomarker for monitoring TGFß1-related events in tendon, as healing and fibrotic scar formation.

Widespread intracranial calcifications in the follow-up of a patient with cartilage-hair hypoplasia--anauxetic dysplasia spectrum disorder: a coincidental finding?

BACKGROUND/PURPOSE: Intracranial calcifications have been identified in many neurological disorders. To our knowledge, however, such findings have not been described in cartilage-hair hypoplasia - anauxetic dysplasia spectrum disorders (CHH-AD), a group of conditions characterized by a wide spectrum of clinical manifestations. METHODS/RESULTS: We report a 22-year old female patient, diagnosed with this disorder during her first year of life, and in whom bilateral intracranial calcifications (frontal lobes, basal ganglia, cerebellar dentate nuclei) were discovered by brain MRI at the age of 17 years. CONCLUSION: The etiology of this finding remains unclear. Some causes of such deposits can be of a reversible nature, thus prompting early recognition although their consequences on clinical outcome remain mostly unknown.

Monoamine oxidase inhibition prevents mitochondrial dysfunction and apoptosis in myoblasts from patients with collagen VI myopathies.

Although mitochondrial dysfunction and oxidative stress have been proposed to play a crucial role in several types of muscular dystrophy (MD), whether a causal link between these two alterations exists remains an open question. We have documented that mitochondrial dysfunction through opening of the permeability transition pore plays a key role in myoblasts from patients as well as in mouse models of MD, and that oxidative stress caused by monoamine oxidases (MAO) is involved in myofiber damage. In the present study we have tested whether MAO-dependent oxidative stress is a causal determinant of mitochondrial dysfunction and apoptosis in myoblasts from patients affected by collagen VI myopathies. We find that upon incubation with hydrogen peroxide or the MAO substrate tyramine myoblasts from patients upregulate MAO-B expression and display a significant rise in reactive oxygen species (ROS) levels, with concomitant mitochondrial depolarization. MAO inhibition by pargyline significantly reduced both ROS accumulation and mitochondrial dysfunction, and normalized the increased incidence of apoptosis in myoblasts from patients. Thus, MAO-dependent oxidative stress is causally related to mitochondrial dysfunction and cell death in myoblasts from patients affected by collagen VI myopathies, and inhibition of MAO should be explored as a potential treatment for these diseases.

Defective collagen VI α6 chain expression in the skeletal muscle of patients with collagen VI-related myopathies.

Collagen VI is a non-fibrillar collagen present in the extracellular matrix (ECM) as a complex polymer; the mainly expressed form is composed of α1, α2 and α3 chains; mutations in genes encoding these chains cause myopathies known as Ullrich congenital muscular dystrophy (UCMD), Bethlem myopathy (BM) and myosclerosis myopathy (MM). The collagen VI α6 chain is a recently identified component of the ECM of the human skeletal muscle. Here we report that the α6 chain was dramatically reduced in skeletal muscle and muscle cell cultures of genetically characterized UCMD, BM and MM patients, independently of the clinical phenotype, the gene involved and the effect of the mutation on the expression of the "classical" α1α2α3 heterotrimer. By contrast, the collagen VI α6 chain was normally expressed or increased in the muscle of patients affected by other forms of muscular dystrophy, the overexpression matching with areas of increased fibrosis. In vitro treatment with TGF-ß1, a potent collagen inducer, promoted the collagen VI α6 chain deposition in the ECM of normal muscle cells, whereas, in cultures derived from collagen VI-related myopathy patients, the collagen VI α6 chain failed to develop a network outside the cells and accumulated in the endoplasmic reticulum. The defect of the α6 chain points to a contribution to the pathogenesis of collagen VI-related disorders.

Whole-body magnetic resonance imaging: an essential tool for diagnosis and work up of non-oncological systemic diseases in children.

AIM: Whole-body MRI (WBMRI) is a non-irradiating imaging technique, suitable to investigate the extent of multisystemic diseases in pediatric patients. However its real impact on diagnosis and management of non-oncological pediatric diseases remains unclear. We present our experience of pediatric WBMRI in various pathologies. METHODS: We retrospectively reviewed medical files of all non- oncologic patients who underwent WBMRI from January 2008 to November 2012. The MRI protocol included T1 weighted and 3D SPACE Inversion Recovery (IR) and fat saturated diffusion weighted (DWI) sequence. We reviewed medical records in order to determine if performing WBMRI added useful information for diagnostic purposes and/or changed clinical management. RESULTS: Forty-two children were included in the study (19 F, 23 M) (median age 4.7 years). Twenty-one children underwent general anesthesia. WBMRI was a useful tool to provide correct diagnosis in chronic recurrent multifocal osteomyelitis (CRMO), and to identify the origin of fever or arthralgia of unknown etiology. WBMRI allowed to determine the extent of disease in juvenile idiopathic arthritis (JIA), chronic granulomatous disorder, enchondromatosis, Langerhans cell histiocytosis, and in the assessment of tumor burden in neurofibromatosis type I. For the battered child syndrome, the influence on management was rather minimal. For each of these pathologies we performed a review of recent literature. CONCLUSION: WBMRI is easy to perform in children and allows the assessment of systemic diseases or discovery of lesions ignored by clinical examination. WBMRI influenced the decisional process and clinical management of various pathologies in our series.

Early-onset or rapidly progressive scoliosis in children: check the eyes!

Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare autosomal recessive disorder characterized by the absence of conjugate horizontal eye movements, and progressive scoliosis developing in childhood and adolescence, caused by mutations in the ROBO3 gene which has an important role in axonal guidance and neuronal migration. We describe two female children aged 12 years and 18 months, with progressive scoliosis, in whom the neurological examination showed absent conjugate horizontal eye movements, but preserved vertical gaze and convergence. Cerebral Magnetic resonance imaging findings included pontine hypoplasia, absent facial colliculi, butterfly configuration of the medulla and a deep midline pontine cleft, while Diffusion tensor imaging (DTI) maps showed the absence of decussating ponto-cerebellar fibers and superior cerebellar peduncles. Somatosensory and motor evoked potential studies demonstrated ipsilateral sensory and motor responses. The diagnosis was confirmed by the identification of bi-allelic mutations in the ROBO3 gene.

Review of the principal extra spinal pathologies causing sciatica and new MRI approaches.

In this paper we illustrate the principal extraspinal pathologies causing sciatica and new approaches for the study of structures such as the lumbosacral plexus (LSP). Visualisation of the LSP in its entirety is difficult with conventional two-dimensional MRI sequences owing to its oblique orientation. In our institution, we have found that the utilisation of three-dimensional short tau inversion-recovery sampling perfection with application-optimised contrasts using different flip angle evolutions sequence is helpful, allowing multiplanar and maximum intensity projection reconstructions in the coronal oblique plane and curvilinear reformats through the plexus. Diffusion tensor imaging enables the observation of microstructural changes and can be useful in surgical planning. The normal anatomy of the LSP, its different extraspinal pathologies and differential diagnoses are thoroughly presented.

Critical evaluation of the use of cell cultures for inclusion in clinical trials of patients affected by collagen VI myopathies.

Collagen VI myopathies (Ullrich congenital muscular dystrophy (UCMD), Bethlem myopathy (BM), and myosclerosis myopathy) share a common pathogenesis, that is, mitochondrial dysfunction due to deregulation of the permeability transition pore (PTP). This effect was first identified in the Col6a1(-/-) mouse model and then in muscle cell cultures from UCMD and BM patients; the normalizing effect of cyclosporin A (CsA) confirmed the pathogenic role of PTP opening. In order to determine whether mitochondrial performance can be used as a criterion for inclusion in clinical trials and as an outcome measure of the patient response to therapy, it is mandatory to establish whether mitochondrial dysfunction is conserved in primary cell cultures from UCMD and BM patients. In this study we report evidence that mitochondrial dysfunction and the consequent increase of apoptotic rate can be detected not only, as previously reported, in muscle, but also in fibroblast cell cultures established from muscle biopsies of collagen VI-related myopathic patients. However, the mitochondrial phenotype is no longer maintained after nine passages in culture. These data demonstrate that the dire consequences of mitochondrial dysfunction are not limited to myogenic cells, and that this parameter can be used as a suitable diagnostic criterion, provided that the cell culture conditions are carefully established.

Prelamin A-mediated recruitment of SUN1 to the nuclear envelope directs nuclear positioning in human muscle.

Lamin A is a nuclear lamina constituent expressed in differentiated cells. Mutations in the LMNA gene cause several diseases, including muscular dystrophy and cardiomyopathy. Among the nuclear envelope partners of lamin A are Sad1 and UNC84 domain-containing protein 1 (SUN1) and Sad1 and UNC84 domain-containing protein 2 (SUN2), which mediate nucleo-cytoskeleton interactions critical to the anchorage of nuclei. In this study, we show that differentiating human myoblasts accumulate farnesylated prelamin A, which elicits upregulation and recruitment of SUN1 to the nuclear envelope and favors SUN2 enrichment at the nuclear poles. Indeed, impairment of prelamin A farnesylation alters SUN1 recruitment and SUN2 localization. Moreover, nuclear positioning in myotubes is severely affected in the absence of farnesylated prelamin A. Importantly, reduced prelamin A and SUN1 levels are observed in Emery-Dreifuss muscular dystrophy (EDMD) myoblasts, concomitant with altered myonuclear positioning. These results demonstrate that the interplay between SUN1 and farnesylated prelamin A contributes to nuclear positioning in human myofibers and may be implicated in pathogenetic mechanisms.