γ-Linolenic acid in maternal milk drives cardiac metabolic maturation.

Birth presents a metabolic challenge to cardiomyocytes as they reshape fuel preference from glucose to fatty acids for postnatal energy production1,2. This adaptation is triggered in part by post-partum environmental changes3, but the molecules orchestrating cardiomyocyte maturation remain unknown. Here we show that this transition is coordinated by maternally supplied γ-linolenic acid (GLA), an 18:3 omega-6 fatty acid enriched in the maternal milk. GLA binds and activates retinoid X receptors4 (RXRs), ligand-regulated transcription factors that are expressed in cardiomyocytes from embryonic stages. Multifaceted genome-wide analysis revealed that the lack of RXR in embryonic cardiomyocytes caused an aberrant chromatin landscape that prevented the induction of an RXR-dependent gene expression signature controlling mitochondrial fatty acid homeostasis. The ensuing defective metabolic transition featured blunted mitochondrial lipid-derived energy production and enhanced glucose consumption, leading to perinatal cardiac dysfunction and death. Finally, GLA supplementation induced RXR-dependent expression of the mitochondrial fatty acid homeostasis signature in cardiomyocytes, both in vitro and in vivo. Thus, our study identifies the GLA-RXR axis as a key transcriptional regulatory mechanism underlying the maternal control of perinatal cardiac metabolism.

Basal joint arthroplasty and carpal tunnel release comparing a single versus double incision: a prospective randomized study.

PURPOSE: Basal thumb joint osteoarthritis frequently coexists with carpal tunnel syndrome. The two conditions have traditionally been treated surgically through separate incisions. We sought to determine whether carpal tunnel release using a single incision during basal joint arthroplasty is as effective as a two-incision approach in patients with concomitant carpal tunnel syndrome and basal thumb joint osteoarthritis. METHODS: For this purpose, 40 patients were randomly allocated to either a single-incision or double-incision approach, all of whom completed the full follow-up period. The Boston Carpal Tunnel Questionnaire, QuickDASH, and a 10-point visual analog scale pain-severity rating were obtained from patients 3, 6 and 12 months post-operatively. RESULTS: The two treatment groups experienced comparable, progressive improvement in all symptom-, function-, and pain-related outcomes, with mean surgery time significantly shorter with the single-incision approach, and four versus zero patients in the double-incision group developing pillar pain (p = 0.035). CONCLUSIONS: Concomitant basal thumb joint osteoarthritis and carpal tunnel syndrome might be effectively performed through a single-incision approach, potentially avoiding any morbidity classically associated with a second incision. LEVEL OF EVIDENCE: Level II/Therapeutic Study. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04391751, 04/29/2020, retrospectively registered.

Effect of vascularized periosteum on revitalization of massive bone isografts: An experimental study in a rabbit model.

INTRODUCTION: In the last years, limb salvage has become the gold standard treatment over amputation. Today, 90% of extremity osteogenic sarcomas can be treated with limb salvage surgery. However, these reconstructions are not exempt from complications. Massive allografts have been associated to high risk of nonunion (12-57%), fracture (7-30%) and infection (5-21%). Association of vascularized periosteum flap to a massive bone allograft (MBA) has shown to halve the average time of allograft union in clinical series, even compared to vascularized fibular flap. Creeping substitution process has been reported in massive allograft when periosteum flap was associated. However, we have little data about whether it results into allograft revitalization. We hypothesize that the association of a periosteum flap to a bone isograft promotes isograft revitalization, defined as the colonization of the devitalized bone by new-form vessels and viable osteocytes, turning it vital. MATERIALS AND METHODS: Forty-four New Zealand white male rabbits underwent a 10 mm segmental radial bone defect. In 24 rabbits the bone excision included the periosteum (controls); in 20 rabbits (periosteum group) bone excision was performed carefully detaching periosteum in order to preserve it. Cryopreserved bone isograft from another rabbit was trimmed and placed to the defect gap and was fixed with a retrograde intramedullar 0.6 mm Kirschner wire. Rabbits were randomized and distributed in 3 subgroups depending on the follow-up (control group: 5 rabbits in 5-week follow up group, 8 rabbits in 10-week follow-up group, 7 rabbits in 20-week follow-up group; periosteum group: 5 rabbits in 5-week follow up group, 7 rabbits in 10-week follow-up group, 7 rabbits in 20-week follow-up group). Fluoroscopic images of rabbit forelimb were taken after sacrifice to address union. Each specimen was blindly evaluated in optical microscope (magnification, ×4) after hematoxylin and eosin staining to qualitative record: presence of new vessels and osteocytes in bone graft lacunae (yes/no) to address revitalization, presence of callus (yes/no) and woven bone and cartilage tissue area (mm2 ) to address remodeling (osteoclast resorption of old bone and substitution by osteoblastic new bone formation). RESULTS: No isograft revitalization occurred in any group, but it was observed bone graft resorption and substitution by new-formed bone in periosteum group. This phenomenon was accelerated in 5-week periosteum group (control group: 49.5 ± 9.6 mm2 vs. periosteum group: 34.9 ± 10.4 mm2 ; p = .07). Remodeled lamellar bone was observed in both 20-week groups (control group: 6.1 ± 6.3 mm2 vs. periosteum group: 5.8 ± 3.0 mm2 , p = .67). Periosteum group showed complete integration and graft substitution, whereas devitalized osteons were still observed in 20-week controls. All periosteum group samples showed radiographic union through a bone callus, whereas controls showed nonunion in eight specimens (Union rate: control group 60% vs. periosteum group 100%, p = .003). CONCLUSIONS: Association of vascularized periosteum to a massive bone isograft has shown to accelerate bone graft substitution into a newly formed bone, thus, no bone graft revitalization occurs.

Vascularized Periosteal Flaps Accelerate Osteointegration and Revascularization of Allografts in Rats.

BACKGROUND: Surgical reconstruction of large bone defects with structural bone allografts can restore bone stock but is associated with complications such as nonunion, fracture, and infection. Vascularized reconstructive techniques may provide an alternative in the repair of critical bone defects; however, no studies specifically addressing the role of vascularized periosteal flaps in stimulating bone allograft revascularization and osseointegration have been reported. QUESTIONS/PURPOSES: (1) Does a vascularized periosteal flap increase the likelihood of union at the allograft-host junction in a critical-size defect femoral model in rats? (2) Does a vascularized periosteal flap promote revascularization of a critical-size defect structural bone allograft in a rat model? (3) What type of ossification occurs in connection with a vascularized periosteal flap? METHODS: Sixty-four rats were assigned to two equal groups. In both the control and experimental groups, a 5-cm critical size femoral defect was created in the left femur and then reconstructed with a cryopreserved structural bone allograft and intramedullary nail. In the experimental group, a vascularized periosteal flap from the medial femoral condyle, with a pedicle based on the descending genicular vessels, was associated with the allograft. The 32 rats of each group were divided into subgroups of 4-week (eight rats), 6-week (eight rats), and 10-week (16 rats) followup. At the end of their assigned followup periods, the animals were euthanized and their femurs were harvested for semiquantitative and quantitative analysis using micro-CT (all followup groups), quantitative biomechanical evaluation (eight rats from each 10-week followup group), qualitative confocal microscopic, backscattered electron microscopic, and histology analysis (4-week and 6-week groups and eight rats from each 10-week followup group). When making their analyses, all the examiners were blinded to the treatment groups from which the samples came. RESULTS: There was an improvement in allograft-host bone union in the 10-week experimental group (odds ratio [OR], 19.29 [3.63-184.50], p < 0.05). In contrast to control specimens, greater bone neoformation in the allograft segment was observed in the experimental group (OR [4-week] 63.3 [39.6-87.0], p < 0.05; OR [6-week] 43.4 [20.5-66.3], p < 0.05; OR [10-week] 62.9 [40.1-85.7], p < 0.05). In our biomechanical testing, control samples were not evaluable as a result of premature breakage during the embedding and assembly processes. Therefore, experimental samples were compared with untreated contralateral femurs. No difference in torsion resistance pattern was observed between both groups. Both backscattered electron microscopy and histology showed newly formed bone tissue and osteoclast lacunae, indicating a regulated process of bone regeneration of the initial allograft in evaluated samples from the experimental group. They also showed intramembranous ossification produced by the vascularized periosteal flap in evaluated samples from the experimental group, whereas samples from the control group showed an attempted endochondral ossification in the allograft-host bone junctions. CONCLUSIONS: A vascularized periosteal flap promotes and accelerates allograft-host bone union and revascularization of cryopreserved structural bone allografts through intramembranous ossification in a preclinical rat model. CLINICAL RELEVANCE: If large-animal models substantiate the findings made here, this approach might be used in allograft reconstructions for critical defects using fibular or tibial periosteal flaps as previously described.

TRest as a New Diagnostic Variable for Chronic Exertional Compartment Syndrome of the Forearm: A Prospective Cohort Analysis of 124 Athletes.

OBJECTIVES: To measure the accuracy of currently used intracompartmental pressure (ICP) diagnostic variables for forearm chronic exertional compartment syndrome (CECS) and a new ICP diagnostic variable, TRest, the recovery time between the maximum ICP and return to resting pressure. DESIGN: Retrospective cohort. Level evidence IV. SETTING: University-affiliated tertiary hospital. PARTICIPANTS: Patients with suspected forearm CECS, 1990 to 2014. INTERVENTIONS: All patients underwent physical examination and exertional stress test, preceded and followed by measuring ICP in all suspicious CECS. Surgery was proposed when indicated. Minimum follow-up was 18 months. Final diagnosis was established at the final follow-up. MAIN OUTCOME MEASURES: Intracompartmental pressure measurements: PRest (baseline/pre-exercise pressure), P1 min (pressure 1 minute after exercise), P5 min (pressure 5 minutes after exercise), and TRest. Patients rated their pain and completed Quick-DASH in all follow-ups. Patients ultimately were classified into 4 groups (true positives, true negatives, false positives, and false negatives) for each ICP measurement relative to the final diagnosis. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. RESULTS: A total of 124 male athletes were diagnosed with CECS, 27 bilateral. Accuracy with standard ICP diagnostic variables was lower (sensitivity 73.5%, specificity 84.2%, positive predictive value 97%, and negative predictive value 31.4%) than with TRest (SN 100%, SP 94.7%, PPV 99.3%, and NPV 100%); 23% of patients would have been missed following the standard ICP diagnostic criteria. CONCLUSIONS: Diagnostic thresholds for current standard ICP measurements should be lowered. TRest, a new measure, might be more accurate.

Analysis of dynamic elbow flexion deformity in children with hemiplegic cerebral palsy.

BACKGROUND: Cerebral palsy affects 1 per 1.000 children, and in 83% of the cases upper extremity is involved. Dynamic elbow flexion deformity is a movement disorder observed in individuals with hemiparesis secondary to cerebral palsy. We sought to determine whether children with hemiplegic cerebral palsy exhibit dynamic elbow flexion deformity during daily activities and its influence to reaching function. METHODS: Sixteen children with upper limb hemiparesis and cerebral palsy (age 11y 7mo (SD 3y 2mo); 11 boys, 5 girls; Gross Motor Function Classification System level I or II) were included in this observational descriptive study. Manual Ability Classification System, Children's Hand-use Experience Questionnaire and Shriners Hospital for Children Upper Extremity Evaluation were used to evaluate affected upper extremity function. Spasticity was assessed with Modified Ashworth scale. Involuntary elbow flexion was recorded in eight daily activities. Elbow motion during reach function was measured. FINDINGS: Fifteen out of 16 individuals showed dynamic elbow flexion deformity. There was a significative increase of involved median elbow flexion in all the activities studied, except for "high speed stairs climbing" evaluation. Children's Hand-use Experience Questionnaire showed that children were independent in most of the daily activities (21 out of 29). Correlation between dynamic elbow flexion deformity and Shriners Hospital for Children Upper Extremity Evaluation was observed only in sitting-standing activity (Spearman's ρ 0.549, P = 0.028). INTERPRETATION: Dynamic elbow flexion deformity is very common in hemiplegic cerebral palsy and occurs proportionally to the degree of the effort demanded by the activities. Despite of presenting this movement disorder, it does not affect in children participation in daily activities.

Analysis of 3 Different Operative Techniques for Extra-articular Fractures of the Phalanges and Metacarpals.

Background: Several techniques have been described for treating metacarpal and phalangeal fractures. We sought to compare the 3 techniques most frequently used for extra-articular metacarpal and phalangeal fractures: plate screw (PS), Kirschner wire (KW), and retrograde intramedullary screw (RIS) fixation. We aimed to determine whether using an RIS provides better clinical outcomes than using either a PS or a KW fixation. Methods: We conducted a retrospective review of patients who underwent surgical treatment of metacarpal and phalangeal fractures from January 2011 to December 2017 in our department. Only patients with an acutely displaced short oblique or transverse extra-articular metacarpal or phalangeal fracture were included. Patients were classified into 3 groups depending on the treatment they received: PS, KW, or RIS fixation. The duration of each procedure was recorded. Clinical assessments included measuring total active motion (TAM), grip strength, and an evaluation of plain radiographs through to ultimate healing. A Disabilities of the Arm, Shoulder and Hand (QuickDASH) score was collected on all patients. Data were analyzed by analysis of variance or Kruskal-Wallis rank test, as indicated. Results: A total of 253 fractures (202 metacarpal and 51 phalangeal) in 230 patients were included in analysis. In all, 135 fractures (53.3%) underwent PS fixation; 53 (20.9%), KW fixation; and 65 (25.6%), RIS fixation. In the KW fixation group, Bouquet pinning was performed for metacarpal fractures and cross pinning for phalangeal fractures. When more than 1 fracture coexisted in the same patient, they were considered separate instances. No differences among the 3 groups were observed when evaluating mean time to radiological union, grip strength, TAM, or QuickDASH score. Mean surgery time was significantly shorter with KW (20 minutes) and RIS (25 minutes), than with PS (32 minutes). Mean return to work or routine activities time was significantly less in the RIS (7.8 weeks) group than in the PS and KW groups (8.3 and 9.2 weeks, respectively). Conclusions: Surgical treatment is recommended in patients with unstable metacarpal and phalangeal fractures. The use of RIS was associated with shorter mean surgery duration and return to work times than PS and KW, respectively.

Trigger Digit Incidence After Carpal Tunnel Release: Reconstruction in Elongated Position Versus Traditional Carpal Tunnel Release.

Background: The development of trigger digit after carpal tunnel syndrome release surgery has been widely reported. Lluch described reconstruction of the flexor retinaculum in elongated position to prevent such complication. Methods: We conducted a retrospective review to determine whether patients who undergo reconstruction in elongated position of the flexor retinaculum have a lower incidence of trigger digit postoperatively. In total, 1050 patients were included, 865 of whom had undergone traditional carpal tunnel release and 185 flexor retinaculum reconstruction. Results: No differences were found in the incidence of trigger digit after surgery (8.7% of the patients who underwent traditional release vs 11.9% in the reconstruction group). Neither difference was found when comparing mean time with the development of trigger digit. Conclusions: In the absence of randomized long-term studies comparing traditional release and reconstruction in elongated position after carpal tunnel release, given our results, we see no reason to favor reconstruction over standard carpal tunnel release as a means to prevent postoperative triggering of digits.

Core Decompression Combined with Implantation of Autologous Bone Marrow Concentrate with Tricalcium Phosphate Does Not Prevent Radiographic Progression in Early Stage Osteonecrosis of the Hip.

BACKGROUD: Untreated osteonecrosis of the femoral head ultimately leads to secondary coxarthrosis. The aim of this study was to determinate if the core decompression of the femoral head combined with implantation of autologous bone marrow concentrate with tricalcium phosphate could be used to prevent radiographic progression of early stage osteonecrosis of the hip. We also sought to determine whether this treatment improved clinical outcomes and reduced the need for total hip arthroplasty. METHODS: Eighteen hips were included in the present study. All of them underwent core decompression of the femoral head combined with implantation of autologous bone marrow concentrate with tricalcium phosphate between 2007 and 2012. The cell concentrate was obtained from the posterior iliac crest and processed and implanted during the same surgical procedure. Patient demographic data, clinical data including modified Harris hip score, and radiological data were collected preoperatively, postoperatively, and during the follow-up period. Also, survival endpoints were analyzed: time of femoral head collapse and need for total hip arthroplasty. RESULTS: The mean age of patients was 37.8 years (standard deviation [SD], 9.31 years). The mean follow-up was 68.9 months (SD, 15.0 months). In most cases (70.6%), the etiology of the osteonecrosis of the femoral head was corticosteroid use; in the remaining cases, secondary to alcohol use. Core decompression of the femoral head combined with implantation of autologous bone marrow concentrate with tricalcium phosphate did not prevent progression to collapse (< 80% at 5 years) although modified Harris hip scores improved. Overall median survival with the total hip arthroplasty as endpoint was 23 months (95% confidence interval [CI], 14.9 to 31.1 months). Overall median survival time with any degree of collapse as endpoint was 7 months (95% CI, 2.0 to 12.0 months). CONCLUSIONS: The results obtained in this study suggest that core decompression combined with implantation of autologous bone marrow concentrate and tricalcium phosphate will not prevent radiographic progression of early stage osteonecrosis of the hip. These finding also suggest that the absence of indications for hip replacement alone is not an indicator of good response to the treatment, and it is important to note the radiological results.

New and safe experimental model of radiation-induced neurovascular histological changes for microsurgical research.

The aim is to create a new and safe experimental model of radiation-induced neurovascular histological changes with reduced morbidity and mortality for use with experimental microsurgical techniques. Seventy-two Sprague-Dawley rats (250-300 g) were divided as follows: Group I: control group, 24 rats clinically evaluated during six weeks; Group II: evaluation of acute side-effects (two-week follow-up period), 24 irradiated (20 Gy) rats; and Group III: evaluation of subacute side-effects (six-week follow-up period), 24 irradiated (20 Gy) rats. Variables included clinical assessments, weight, vascular permeability (arterial and venous), mortality and histological studies. No significant differences were observed between groups with respect to the variables studied. Significant differences were observed between groups I vs II-III regarding survival rates and histological changes to arteries, veins and nerves. Rat body weights showed progressive increases in all groups, and the mortality rate of the present model is 10.4% compared with 30-40% in the previous models. In conclusion, the designed model induces selective changes by radiotherapy in the neurovascular bundle without histological changes affecting the surrounding tissues. This model allows therapeutic experimental studies to be conducted, including the viability of microvascular and microneural sutures post radiotherapy in the cervical neurovascular bundle.

Effect of Previous Irradiation on Vascular Thrombosis of Microsurgical Anastomosis: A Preclinical Study in Rats.

BACKGROUND: The objective of the present investigation was to compare the effect of neoadjuvant irradiation on the microvascular anastomosis in cervical bundle using an experimental model in rats. METHODS: One hundred forty male Sprague-Dawley rats were allocated into 4 groups: group I, control, arterial microanastomosis; group II, control, venous microanastomosis; group III, arterial microanastomosis with previous irradiation (20 Gy); and group IV, venous microanastomosis with previous irradiation (20 Gy). Clinical parameters, technical values of anastomosis, patency, and histopathological parameters were evaluated. RESULTS: Irradiated groups (III and IV) and vein anastomosis groups (II and IV) showed significantly increased technical difficulties. Group IV showed significantly reduced patency rates (7/35) when compared with the control group (0/35). Radiotherapy significantly decreased the patency rates of the vein (7/35) when compared with the artery (1/35). Groups III and IV showed significantly reduced number of endothelial cells and also showed the presence of intimal thickening and adventitial fibrosis as compared with the control group. CONCLUSION: Neoadjuvant radiotherapy reduces the viability of the venous anastomosis in a preclinical rat model with a significant increase in the incidence of vein thrombosis.

Increased infection risk after hip hemiarthroplasty in institutionalized patients with proximal femur fracture.

In patients undergoing hip hemiarthroplasty (HHA) secondary to proximal femur fracture, acute periprosthetic joint infection (PJI) is one of the most important complications. We have detected an increased risk of PJI in chronic institutionalized patients (CIPs), and a higher number of early postoperative infections are caused by Gram-negative bacteria (GNB), not covered by the current prophylaxis (cefazolin in noninstitutionalized patients (NIPs) and cotrimoxazole in CIPs). We sought to compare infection characteristics between NIPs and CIPs, analyzing predisposing factors, causative pathogens, and antibiotic prophylaxis-related microbiological characteristics. We performed a retrospective review of our prospective institutional database to identify all patients consecutively admitted for HHA to treat proximal femur fracture at our centre between 2011 and 2013. PJI was diagnosed in 21 of 381 (5.51%) patients, with 10 of 105 (9.52%) in the CIP group and 11 of 276 (3.99%) in the NIP group, and statistical significance was achieved. GNB accounted for PJI in 14 (66.67%) patients. We detected a single case of methicillin-resistant Staphylococcus aureus (MRSA) infection in the NIP group. We confirm a higher risk of acute PJI among institutionalized patients, commonly caused by Gram-negative microorganisms, which are not covered by the current prophylaxis. New prophylactic strategies should be investigated in order to reduce this problem.