Protein synthesis rates of muscle, tendon, ligament, cartilage, and bone tissue in vivo in humans

Skeletal muscle plasticity is reflected by a dynamic balance between protein synthesis and breakdown, with basal muscle tissue protein synthesis rates ranging between 0.02 and 0.09%/h. Though it is evident that other musculoskeletal tissues should also express some level of plasticity, data on protein synthesis rates of most of these tissues in vivo in humans is limited. Six otherwise healthy patients (62±3 y), scheduled to undergo unilateral total knee arthroplasty, were subjected to primed continuous intravenous infusions with L-[ring-13C6]-Phenylalanine throughout the surgical procedure. Tissue samples obtained during surgery included muscle, tendon, cruciate ligaments, cartilage, bone, menisci, fat, and synovium. Tissue-specific fractional protein synthesis rates (%/h) were assessed by measuring the incorporation of L-[ring-13C6]-Phenylalanine in tissue protein and were compared with muscle tissue protein synthesis rates using a paired t test. Tendon, bone, cartilage, Hoffa’s fat pad, anterior and posterior cruciate ligament, and menisci tissue protein synthesis rates averaged 0.06±0.01, 0.03±0.01, 0.04±0.01, 0.11±0.03, 0.07±0.02, 0.04±0.01, and 0.04±0.01%/h, respectively, and did not significantly differ from skeletal muscle protein synthesis rates (0.04±0.01%/h; P>0.05). Synovium derived protein (0.13±0.03%/h) and intercondylar notch bone tissue protein synthesis rates (0.03±0.01%/h) were respectively higher and lower compared to skeletal muscle protein synthesis rates (P<0.05 and P<0.01, respectively). Basal protein synthesis rates in various musculoskeletal tissues are within the same range of skeletal muscle protein synthesis rates, with fractional muscle, tendon, bone, cartilage, ligament, menisci, fat, and synovium protein synthesis rates ranging between 0.02 and 0.13% per hour in vivo in humans

Percutaneous radiofrequency lesions adjacent to the dorsal root ganglion alleviate spasticity and pain in children with cerebral palsy: pilot study in 17 patients

BACKGROUND: Cerebral palsy (CP) may cause severe spasticity, requiring neurosurgical procedures. The most common neurosurgical procedures are continuous infusion of intrathecal baclofen and selective dorsal rhizotomy. Both are invasive and complex procedures. We hypothesized that a percutaneous radiofrequency lesion of the dorsal root ganglion (RF-DRG) could be a simple and safe alternative treatment. We undertook a pilot study to test this hypothesis. METHODS: We performed an RF-DRG procedure in 17 consecutive CP patients with severe hip flexor/adductor spasms accompanied by pain or care-giving difficulties. Six children were systematically evaluated at baseline, and 1 month and 6 months after treatment by means of the Modified Ashworth Scale (MAS), Gross Motor Function Measure (GMFM) and a self-made caregiver's questionnaire. Eleven subsequent children were evaluated using a Visual Analogue Scale (VAS) for spasticity, pain and ease of care. RESULTS: A total of 19 RF-DRG treatments were performed in 17 patients. We found a small improvement in muscle tone measured by MAS, but no effect on the GMFM scale. Despite this, the caregivers of these six treated children unanimously stated that the quality of life of their children had indeed improved after the RF-DRG. In the subsequent 11 children we found improvements in all VAS scores, in a range comparable to the conventional treatment options. CONCLUSION: RF-DRG is a promising new treatment option for severe spasticity in CP patients, and its definitive effectiveness remains to be defined in a randomised controlled trial

Carbon-Fiber-Reinforced PEEK Intramedullary Nails Defining the Niche

Background. Carbon-fiber-reinforced Polyetheretherketone (CFR-PEEK) nails are gaining interest as they have biomechanical properties potentially capable of overcoming disadvantages of conventional metal nails. Case Summary. Three cases are illustrated which required superior mechanical toughness, compatibility with radiotherapy, and postoperative advanced imaging. Conclusion. CFR-PEEK nails seem to have a niche role in distinct groups of patients

Returning to Elective Orthopedic Surgery During the COVID-19 Pandemic: A Multidisciplinary and Pragmatic Strategy for Initial Patient Selection

OBJECTIVE: The aim of the study was to design an objective, transparent, pragmatic, and flexible workflow to assist with patient selection during the initial phase of return to elective orthopedic surgery during the COVID-19 pandemic with the main purpose of enhancing patient safety. METHODS: A multidisciplinary working group was formed consisting of representatives for orthopedics, epidemiology, ethics, infectious diseases, cardiovascular diseases, and intensive care medicine. Preparation for upcoming meetings consisted of reading up on literature and testing of proposed methodologies on our own waiting lists. RESULTS: A workflow based on 3 domains, that is, required resources, patient fitness, and time sensitivity of the procedure, was considered most useful. All domains function as standalones, in a specific order, and no sum score is used. The domain of required resources demands input from the surgical team, results in a categorical (yes or no) outcome, and generates a list of potential patients who can be scheduled for surgery under these particular circumstances. The (weighted) items for the domain of patient fitness are the same for every patient, are scored on a numerical scale, but are likely to change during the pandemic as more data become available. Time sensitivity of the procedure is again scored on a numerical scale and becomes increasingly important when returning to elective surgery proves to be acceptably safe. After patient selection, an augmented informed consent, screening, and testing according to local guidelines will take place. CONCLUSIONS: A workflow is proposed for patient selection aiming for the safest possible return to elective orthopedic surgery during the COVID-19 pandemic.status: publishe

Clinical and Molecular Phenotype of Aicardi-Goutières Syndrome

Aicardi-Goutières syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3′→5′ exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNASEH2B, and RNASEH2C were observed in 31, 3, 47, and 18 families, respectively. In five families, we identified an RNASEH2A or RNASEH2B mutation on one allele only. In one child, the disease occurred because of a de novo heterozygous TREX1 mutation. In 22 families, no mutations were found. Null mutations were common in TREX1, although a specific missense mutation was observed frequently in patients from northern Europe. Almost all mutations in RNASEH2A, RNASEH2B, and RNASEH2C were missense. We identified an RNASEH2C founder mutation in 13 Pakistani families. We also collected clinical data from 123 mutation-positive patients. Two clinical presentations could be delineated: an early-onset neonatal form, highly reminiscent of congenital infection seen particularly with TREX1 mutations, and a later-onset presentation, sometimes occurring after several months of normal development and occasionally associated with remarkably preserved neurological function, most frequently due to RNASEH2B mutations. Mortality was correlated with genotype; 34.3% of patients with TREX1, RNASEH2A, and RNASEH2C mutations versus 8.0% RNASEH2B mutation–positive patients were known to have died (P=.001). Our analysis defines the phenotypic spectrum of AGS and suggests a coherent mutation-screening strategy in this heterogeneous disorder. Additionally, our data indicate that at least one further AGS-causing gene remains to be identified