Does Retrograde Femoral Nailing through a Normal Physis Impair Growth?:An Experimental Porcine Model

MATERIALS AND METHODS: The study was carried out using an experimental porcine model. Eleven juvenile female porcines were randomized for insertion of a retrograde femoral nail in one limb. The other limb acted as a control. The animals were housed for 8 weeks before the nail was removed and housed for 8 additional weeks, that is, 16 weeks in total. Growth was assessed by interphyseal distance on 3D magnetic resonance imaging (MRI) after 16 weeks and the operated limb was compared to the non-operated limb. Histomorphometric analysis of the physeal canal was performed. RESULTS: No difference in longitudinal growth was observed when comparing the operated femur to the non-operated femur using MRI after 16 weeks. No osseous tissue crossing the physis was observed on MRI or histology. The empty canal in the physis after nail removal was filled with fibrous tissue 16 weeks after primary surgery. CONCLUSION: Growth was not impaired and no bone bridges were seen on MRI or histology 16 weeks after insertion and later removal of the retrograde femoral nail. CLINICAL SIGNIFICANCE: The insertion of a retrograde intramedullary femoral nail centrally through the physis and later removal might be safe, however, long-term follow-up is needed. AIM AND OBJECTIVE: The insertion of an intramedullary nail may be beneficial in certain cases of leg length discrepancy (LLD) in children. However, it is unknown if the physeal injury due to the surgery may cause bone bridge formation and thereby growth arrest after removal. This study aimed to assess longitudinal interphyseal growth 16 weeks after insertion and later removal of a retrograde femoral nail passing through the physis. Moreover, to analyse the tissue forming in the empty physeal canal after removal of the nail. HOW TO CITE THIS ARTICLE: Abood AA, Rahbek O, Olesen ML, et al. Does Retrograde Femoral Nailing through a Normal Physis Impair Growth? An Experimental Porcine Model. Strategies Trauma Limb Reconstr 2021;16(1):8–13

Reversible insulin resistance in muscle and fat unrelated to the metabolic syndrome in patients with acromegaly

BACKGROUND: Patients with active acromegaly exhibit insulin resistance despite a lean phenotype whereas controlled disease improves insulin sensitivity and increases fat mass. The mechanisms underlying this paradox remain elusive, but growth hormone (GH)-induced lipolysis plays a central role. The aim of the study was to investigative the molecular mechanisms of insulin resistance dissociated from obesity in patients with acromegaly. METHODS: In a prospective study, twenty-one patients with newly diagnosed acromegaly were studied at diagnosis and after disease control obtained by either surgery alone (n=10) or somatostatin analogue (SA) treatment (n=11) with assessment of body composition (DXA scan), whole body and tissue-specific insulin sensitivity and GH and insulin signalling in adipose tissue and skeletal muscle. FINDINGS: Disease control of acromegaly significantly reduced lean body mass (p<0.001) and increased fat mass (p<0.001). At diagnosis, GH signalling (pSTAT5) was constitutively activated in fat and enhanced expression of GH-regulated genes (CISH and IGF-I) were detected in muscle and fat. Insulin sensitivity in skeletal muscle, liver and adipose tissue increased after disease control regardless of treatment modality. This was associated with enhanced insulin signalling in both muscle and fat including downregulation of phosphatase and tensin homolog (PTEN) together with reduced signalling of GH and lipolytic activators in fat. INTERPRETATION: In conclusion, the study support that uncontrolled lipolysis is a major feature of insulin resistance in active acromegaly, and is characterized by upregulation of PTEN and suppression of insulin signalling in both muscle and fat. FUNDING: This work was supported by a grant from the Independent Research Fund, Denmark (7016-00303A) and from the Alfred Benzon Foundation, Denmark

Major Cardiac Events in Patients and Relatives With Hereditary Hypertrophic Cardiomyopathy

BackgroundLittle evidence is available on the disease expression in relatives of index patients with hypertrophic cardiomyopathy (HCM). This information has important implications for family screening programs, genetic counseling, and management of affected families.ObjectivesThe purpose of this study was to investigate the disease expression and penetrance in relatives of index patients carrying pathogenic/likely pathogenic (P/LP) variants in recognized HCM genes.MethodsA total of 453 consecutive and unrelated HCM index patients underwent clinical and genetic investigations. A total of 903 relatives of genotype-positive index patients were invited for clinical investigations and genetic testing. Penetrance, disease expression, and incidence rates of major adverse cardiac events (MACEs) were investigated in individuals carrying P/LP variants.ResultsForty percent (183/453) of index patients carried a P/LP variant. Eighty-four percent (757/903) of all relatives of index patients with P/LP variants were available for the investigation, of whom 54% (407/757) carried a P/LP variant. The penetrance of HCM among relatives was 39% (160/407). Relatives with HCM and index patients were diagnosed at a similar age (43 ± 18 years vs 46 ± 15 years; P = 0.11). There were no differences in clinical characteristics or incidence rates of MACE during 8 years of follow-up.ConclusionsThe disease expression of HCM among index patients and affected relatives carrying P/LP variants in recognized disease genes was similar, with an equal risk of experiencing MACE. These findings provide evidence to support family screening and follow-up of genotype-positive HCM families to improve management and diminish the number of adverse disease complications among relatives

Carbon black nanoparticle instillation induces sustained inflammation and genotoxicity in mouse lung and liver

<p>Abstract</p> <p>Background</p> <p>Widespread occupational exposure to carbon black nanoparticles (CBNPs) raises concerns over their safety. CBNPs are genotoxic <it>in vitro </it>but less is known about their genotoxicity in various organs <it>in vivo</it>.</p> <p>Methods</p> <p>We investigated inflammatory and acute phase responses, DNA strand breaks (SB) and oxidatively damaged DNA in C57BL/6 mice 1, 3 and 28 days after a single instillation of 0.018, 0.054 or 0.162 mg Printex 90 CBNPs, alongside sham controls. Bronchoalveolar lavage (BAL) fluid was analyzed for cellular composition. SB in BAL cells, whole lung and liver were assessed using the alkaline comet assay. Formamidopyrimidine DNA glycosylase (FPG) sensitive sites were assessed as an indicator of oxidatively damaged DNA. Pulmonary and hepatic acute phase response was evaluated by <it>Saa3 </it>mRNA real-time quantitative PCR.</p> <p>Results</p> <p>Inflammation was strongest 1 and 3 days post-exposure, and remained elevated for the two highest doses (i.e., 0.054 and 0.162 mg) 28 days post-exposure (P < 0.001). SB were detected in lung at all doses on post-exposure day 1 (P < 0.001) and remained elevated at the two highest doses until day 28 (P < 0.05). BAL cell DNA SB were elevated relative to controls at least at the highest dose on all post-exposure days (P < 0.05). The level of FPG sensitive sites in lung was increased throughout with significant increases occurring on post-exposure days 1 and 3, in comparison to controls (P < 0.001-0.05). SB in liver were detected on post-exposure days 1 (P < 0.001) and 28 (P < 0.001). Polymorphonuclear (PMN) cell counts in BAL correlated strongly with FPG sensitive sites in lung (r = 0.88, P < 0.001), whereas no such correlation was observed with SB (r = 0.52, P = 0.08). CBNP increased the expression of <it>Saa3 </it>mRNA in lung tissue on day 1 (all doses), 3 (all doses) and 28 (0.054 and 0.162 mg), but not in liver.</p> <p>Conclusions</p> <p>Deposition of CBNPs in lung induces inflammatory and genotoxic effects in mouse lung that persist considerably after the initial exposure. Our results demonstrate that CBNPs may cause genotoxicity both in the primary exposed tissue, lung and BAL cells, and in a secondary tissue, the liver.</p