Muscle involvement in systemic sclerosis: high mortality not associated with nature of histological lesions.

OBJECTIVES: The aim of this study was to determine the association between different histological patterns and prognosis in patients with SSc and histologically proven muscle involvement. METHODS: A multicentre retrospective study was conducted of a cohort of scleroderma patients who had undergone muscle biopsy. The biopsies were reviewed in a coordinated manner to classify patients based on histological findings. Three different patterns were observed: fibrosing myopathy (FM), inflammatory myopathy (IM) and necrotizing myopathy (NM). Rates of survival, muscle relapse, and cardiac and pulmonary events were compared between these three groups. RESULTS: Among 71 scleroderma patients with muscle biopsy specimens available for review, 33 (46.5%) were classified in the FM group, 18 (25.5%) in the IM group, and 20 (28%) in the NM group. The median follow-up time was 6.4 years (interquartile range, 2.2-10.9 years) and 21 patients died during follow-up, primarily from heart disease and infections. The 10-year survival rate after the first non-Raynaud's disease symptom was 80% and the cumulative incidence of muscle relapse was 25%. Neither factor differed significantly between the three groups. The risk of pulmonary events was lowest in the OM group, significantly lower than in the FM group (hazard ratio, 0.17; 95% CI, 0.04-0.67) and non-significantly lower than in the IMNM group (hazard ratio, 0.28; 95% CI, 0.06-1.24). The risk of cardiac events did not differ significantly between the three groups. CONCLUSION: The mortality rate of scleroderma patients with muscle involvement was not associated with their histological patterns.

Receptor interacting protein kinase-3 mediates both myopathy and cardiomyopathy in preclinical animal models of Duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a progressive muscle degenerative disorder, culminating in a complete loss of ambulation, hypertrophic cardiomyopathy and a fatal cardiorespiratory failure. Necroptosis is the form of necrosis that is dependent upon the receptor-interacting protein kinase (RIPK) 3; it is involved in several inflammatory and neurodegenerative conditions. We previously identified RIPK3 as a key player in the acute myonecrosis affecting the hindlimb muscles of the mdx dystrophic mouse model. Whether necroptosis also mediates respiratory and heart disorders in DMD is currently unknown. METHODS: Evidence of activation of the necroptotic axis was examined in dystrophic tissues from Golden retriever muscular dystrophy (GRMD) dogs and R-DMDdel52 rats. A functional assessment of the involvement of necroptosis in dystrophic animals was performed on mdx mice that were genetically depleted for RIPK3. Dystrophic mice aged from 12 to 18 months were analysed by histology and molecular biology to compare the phenotype of muscles from mdxRipk3+/+ and mdxRipk3-/- mice. Heart function was also examined by echocardiography in 40-week-old mice. RESULTS: RIPK3 expression in sartorius and biceps femoris muscles from GRMD dogs positively correlated to myonecrosis levels (r = 0.81; P = 0.0076). RIPK3 was also found elevated in the diaphragm (P ≤ 0.05). In the slow-progressing heart phenotype of GRMD dogs, the phosphorylated form of RIPK1 at the Serine 161 site was dramatically increased in cardiomyocytes. A similar p-RIPK1 upregulation characterized the cardiomyocytes of the severe DMDdel52 rat model, associated with a marked overexpression of Ripk1 (P = 0.007) and Ripk3 (P = 0.008), indicating primed activation of the necroptotic pathway in the dystrophic heart. MdxRipk3-/- mice displayed decreased compensatory hypertrophy of the heart (P = 0.014), and echocardiography showed a 19% increase in the relative wall thickness (P < 0.05) and 29% reduction in the left ventricle mass (P = 0.0144). Besides, mdxRipk3-/- mice presented no evidence of a regenerative default or sarcopenia in skeletal muscles, moreover around 50% less affected by fibrosis (P < 0.05). CONCLUSIONS: Our data highlight molecular and histological evidence that the necroptotic pathway is activated in degenerative tissues from dystrophic animal models, including the diaphragm and the heart. We also provide the genetic proof of concept that selective inhibition of necroptosis in dystrophic condition improves both histological features of muscles and cardiac function, suggesting that prevention of necroptosis is susceptible to providing multiorgan beneficial effects for DMD.

Unfractionated Bulk Culture of Mouse Skeletal Muscle to Recapitulate Niche and Stem Cell Quiescence.

Skeletal muscle is the largest tissue of the body and performs multiple functions, from locomotion to body temperature control. Its functionality and recovery from injuries depend on a multitude of cell types and on molecular signals between the core muscle cells (myofibers, muscle stem cells) and their niche. Most experimental settings do not preserve this complex physiological microenvironment, and neither do they allow the ex vivo study of muscle stem cells in quiescence, a cell state that is crucial for them. Here, a protocol is outlined for the ex vivo culture of muscle stem cells with cellular components of their niche. Through the mechanical and enzymatic breakdown of muscles, a mixture of cell types is obtained, which is put in 2D culture. Immunostaining shows that within 1 week, multiple niche cells are present in culture alongside myofibers and, importantly, Pax7-positive cells that display the characteristics of quiescent muscle stem cells. These unique properties make this protocol a powerful tool for cell amplification and the generation of quiescent-like stem cells that can be used to address fundamental and translational questions.

TEVAR Stent to the False Lumen of a Chronic Type B Aortic Dissection With Aneurysmal Dilatation, When no Other Options Are Left.

We report a case of a 72 years-old male referred to us with a 2-year history of an enlarging aortic aneurysm secondary to a chronic Type B aortic dissection and a complete occlusion of the true lumen in the thoracic and abdominal aorta except at the level of visceral arteries origins. Several attempts to recanalize the true lumen was not successful. Because of the patient's high risk for an open repair and the normal size of his thoracic aorta proximal to the celiac artery, we deployed the TEVAR stent to the false lumen to prevent aneurysmal enlargement and rupture. The operation was successful, and the patient recovered without complications and with complete exclusion of the aneurysm on two years follow up.

Isolated Idiopathic Right Common Iliac Artery Aneurysm Presenting as Acute Appendicitis in a 9-Year-Old Girl: A Case Report and Literature Review.

The prevalence of iliac artery aneurysms is extremely rare in children. The most common etiologies for developing an aneurysm in children are infections, inflammatory diseases, and trauma. An idiopathic or congenital etiology is the least common cause in the pediatric population. We report a case of a 9-year-old girl with no previous history of trauma, intervention, or family history of vascular diseases who presented with a sudden severe right lower quadrant pain suggesting appendicitis. Upon examination, a large tender pulsatile mass was felt in the right lower quadrant. Ultrasound and computed tomography scans revealed a large right common iliac aneurysm. The aneurysm was noted to have a high risk of rupture due to the sudden symptomatic presentation and its large size. Therefore, the patient underwent an urgent operation, during which an aneurysmal repair was performed with an interposition graft. Postoperative ultrasound imaging showed a patent graft and no residual aneurysm. The patient has been followed up for two years, and no complications were found.

Long standing biliary colic masking chylous ascites in laparoscopic roux-en-Y gastric bypass; a case report.

BACKGROUND: Chylous ascites is considered to be an intra-abdominal collection of creamy colored fluid with triglyceride content of > 110 mg/dL. Chylous ascites is an uncommon but serious complication of numerous surgical interventions. However, it is a rare complication of LRYGB. An internal hernia limb defect is thought to be the underlying etiology, where the hernia will cause lymphatic vessel engorgement and lymphatic extravasation. CASE PRESENTATION: We report a case of a 29 years old male with a 9 year history of laparoscopic Roux en y gastric bypass (LRGYB), presenting with recurrent abdominal pain for 2 months radiating to the right shoulder. Ultrasound examination revealed gallstones and the patient was subsequently admitted for laparoscopic cholecystectomy. Intraoperatively, whitish colored fluid, high in triglycerides content was aspirated. During exploration, an internal hernia limb defect was found and corrected. CONCLUSION: Post LRGYB patients with symptoms of recurrent abdominal pain should be suspected for chylous ascites reflecting an internal hernia.