Executive summary: Guidelines for the diagnosis and treatment of septic arthritis in adults and children, developed by the GEIO (SEIMC), SEIP and SECOT.

Infection of a native joint, commonly referred to as septic arthritis, is a medical emergency because of the risk of joint destruction and subsequent sequelae. Its diagnosis requires a high level of suspicion. These guidelines for the diagnosis and treatment of septic arthritis in children and adults are intended for use by any physician caring for patients with suspected or confirmed septic arthritis. They have been developed by a multidisciplinary panel with representatives from the Bone and Joint Infections Study Group (GEIO) belonging to the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Paediatric Infections (SEIP) and the Spanish Society of Orthopaedic Surgery and Traumatology (SECOT), and two rheumatologists. The recommendations are based on evidence derived from a systematic literature review and, failing that, on the opinion of the experts who prepared these guidelines. A detailed description of the background, methods, summary of evidence, the rationale supporting each recommendation, and gaps in knowledge can be found online in the complete document.

Lateralized overgrowth as a guiding sign of abdominal neoplasms for pediatric orthopedic surgeons.

OBJECTIVES: This study aims to increase the awareness of the association between lateralized overgrowth (LO) and abdominal tumor among the pediatric orthopedic community and to evaluate its incidence in our center. PATIENTS AND METHODS: Between January 1997 and December 2021, a total of 166 patients with Wilms tumors and hepatoblastomas were retrospectively analyzed. Data including age, sex, initial clinical signs (hematuria, abdominal mass with or without general discomfort), type of asymmetric regional body overgrowth (isolated or in relation with any syndrome), and tumor stage at diagnosis were recorded. In addition, age at which asymmetric regional body overgrowth was described and age at the time of tumor diagnosis were noted. RESULTS: Of a total of 166 patients, 133 were diagnosed with Wilms tumors (nephroblastomas) and 33 were diagnosed with hepatoblastomas. In 94% of the cases, the initial clinical signs were an abdominal mass and/or hematuria. Overall, five (3%) patients presented with LO. Four patients with Wilms tumor presented it at the initial clinical examinations. In three of these cases (2.3%), we found it isolated and, in the remaining patient (0.75%), it was associated with Beckwith-Wiedemann spectrum. Only one patient affected from hepatoblastoma (3%) presented with an isolated LO at the time of tumor diagnosis. CONCLUSION: Our study results show an incidence of LO in relation to intra-abdominal tumors of 3%. The latest updates recommend genetic testing to identify subgroups with a higher risk for tumor development that are more likely to benefit from tumor protocol surveillance.

Poland syndrome: a new classification system based on a retrospective analysis of 74 cases.

LEVEL OF EVIDENCE: III.

Seymour fracture: Better do not underestimate it.

OBJECTIVES: This study aims to analyze the functional results, management, and complications of acute Seymour fracture treatment and to generalize the understanding of Seymour fractures, as well as awareness about its controversial treatment and critical sequelae. PATIENTS AND METHODS: Between January 1994 and December 2019, a total of 29 patients (20 males, 9 females; mean age: 7.9±3.9 years; range, 1 to 15 years) who presented within the first 24 h of injury and were diagnosed with Seymour fractures and treated in the emergency setting were retrospectively analyzed. Clinical and radiological data were collected from medical records at the time of diagnosis and during follow-up, within a week after the treatment and in the visits required until fracture healing, and no sequelae were observed. In the event of complications, a minimum of one year of follow-up was carried out. Radiographs were taken of the anteroposterior and lateral views during each visit. RESULTS: The mean follow-up was 10.8±8.6 (range, 2 to 36) months. Surgical treatment in the operating room was performed in 24 (82.7%) patients using a single longitudinal Kirschner wire (K-wire) fixation through the distal phalanx and the distal interphalangeal joint in 21 patients. Non-operative treatment based on closed reduction and splinting was performed in five (17.3%) patients. There was no statistically significant difference in the final passive range of motion and physeal growth arrest in relation to the use or non-use of K-wires. The use of antibiotics in any of the three possible administrations (intravenous antibiotic regimen, intravenous and later oral antibiotic at-home or oral antibiotics), in relation to the non-use of antibiotics seemed to be a protective factor against infections (odds ratio=0.04; 95% confidence interval: 0.006-0.2; p=0.001). CONCLUSION: The identification of Seymour fractures is crucial for applying the correct treatment and reducing the risk of complications, such as osteomyelitis and physeal alterations. Based on our study results, we can suggest that the use of an antibiotic regimen causes a lower risk of infections in acute Seymour fractures. The prompt identification of these fractures with a standardized protocol covering irrigation, debridement, reduction, fixation, and prophylactic antibiotics is needed to avoid complications.

Elbow flexion reconstruction with nerve transfer or grafting in patients with brachial plexus injuries: A systematic review and comparison study.

INTRODUCTION: Posttraumatic brachial plexus (BP) palsy was used to be treated by reconstruction with nerve grafts. For the last two decades, nerve transfers have gained popularity and believed to be more effective than nerve grafting. The aim of this systematic review was to compare elbow flexion restoration with nerve transfers or nerve grafting after traumatic BP injury. METHODS: PRISMA-IPD structure was used for 52 studies included. Patients were allocated as C5-C6 (n = 285), C5-C6-C7 (n = 150), and total BP injury (n = 245) groups. In each group, two treatment modalities were compared, and effects of age and preoperative interval were analyzed. RESULTS: In C5-C6 injuries, 93.1% of nerve transfer patients achieved elbow flexion force ≥M3, which was significantly better when compared to 69.2% of nerve graft patients (p < 0.001). For improved outcomes of nerve transfer patients, shorter preoperative interval was a significant factor in all injury patterns (p < 0.001 for C5-C6 injuries and total BP injuries, p = 0.018 for C5-C6-C7 injuries), and young age was a significant factor in total BP injury pattern (p = 0.022). CONCLUSIONS: Our analyses showed that nerve transfers appear superior to nerve graftings especially in patients with a C5-C6 injury. Unnecessary delays in surgery must be prevented, and younger patients may have more chance for better recovery. LEVEL OF EVIDENCE: Level II.

Assessment of biodistribution using mesenchymal stromal cells: Algorithm for study design and challenges in detection methodologies.

BACKGROUND AIMS: Biodistribution of candidate cell-based therapeutics is a critical safety concern that must be addressed in the preclinical development program. We aimed to design a decision tree based on a series of studies included in actual dossiers approved by competent regulatory authorities, noting that the design, execution and interpretation of pharmacokinetics studies using this type of therapy is not straightforward and presents a challenge for both developers and regulators. METHODS: Eight studies were evaluated for the definition of a decision tree, in which mesenchymal stromal cells (MSCs) were administered to mouse, rat and sheep models using diverse routes (local or systemic), cell labeling (chemical or genetic) and detection methodologies (polymerase chain reaction [PCR], immunohistochemistry [IHC], fluorescence bioimaging, and magnetic resonance imaging [MRI]). Moreover, labeling and detection methodologies were compared in terms of cost, throughput, speed, sensitivity and specificity. RESULTS: A decision tree was defined based on the model chosen: (i) small immunodeficient animals receiving heterologous MSC products for assessing biodistribution and other safety aspects and (ii) large animals receiving homologous labeled products; this contributed to gathering data not only on biodistribution but also on pharmacodynamics. PCR emerged as the most convenient technique despite the loss of spatial information on cell distribution that can be further assessed by IHC. DISCUSSION: This work contributes to the standardization in the design of biodistribution studies by improving methods for accurate assessment of safety. The evaluation of different animal models and screening of target organs through a combination of techniques is a cost-effective and timely strategy.

Isolation, characterization, and differentiation of multipotent neural progenitor cells from human cerebrospinal fluid in fetal cystic myelomeningocele.

Despite benefits of prenatal in utero repair of myelomeningocele, a severe type of spina bifida aperta, many of these patients will still suffer mild to severe impairment. One potential source of stem cells for new regenerative medicine-based therapeutic approaches for spinal cord injury repair is neural progenitor cells (NPCs) in cerebrospinal fluid (CSF). To this aim, we extracted CSF from the cyst surrounding the exposed neural placode during the surgical repair of myelomeningocele in 6 fetuses (20 to 26weeks of gestation). In primary cultured CSF-derived cells, neurogenic properties were confirmed by in vitro differentiation into various neural lineage cell types, and NPC markers expression (TBR2, CD15, SOX2) were detected by immunofluorescence and RT-PCR analysis. Differentiation into three neural lineages was corroborated by arbitrary differentiation (depletion of growths factors) or explicit differentiation as neuronal, astrocyte, or oligodendrocyte cell types using specific induction mediums. Differentiated cells showed the specific expression of neural differentiation markers (ßIII-tubulin, GFAP, CNPase, oligo-O1). In myelomeningocele patients, CSF-derived cells could become a potential source of NPCs with neurogenic capacity. Our findings support the development of innovative stem-cell-based therapeutics by autologous transplantation of CSF-derived NPCs in damaged spinal cords, such as myelomeningocele, thus promoting neural tissue regeneration in fetuses.

Femoral head bone viability after free vascularized fibular grafting for osteonecrosis: SPECT/CT study.

PURPOSE: To evaluate femoral head bone viability following free vascularized fibular grafting (FVFG) for osteonecrosis using SPECT/CT imaging. METHODS: Ten hips (9 patients) with osteonecrosis of the femoral head (ONFH) undergoing FVFG were prospectively enrolled. Four cases showed ARCO stage II, while six showed ARCO stage III. The mean age at surgery was 15.7 years (range, 13-22 years). Hip Harris Score (HHS) was measured pre- and post-operative. Bone scintigraphy with SPECT/CT was performed at 2 weeks and 6 months following surgery. RESULTS: Mean follow-up was 4.0 years (range, 2-5.9 years). Mean HHS increased from 37.2 to 92.3. SPECT/CT findings revealed a progressive increase of femoral head uptake in all cases, suggesting subchondral graft bone viability. No progressive deformation of the femoral head was evidenced in radiographic evaluation at final follow-up. CONCLUSIONS: This study demonstrates FVFG's capacity for revitalizing femoral head subchondral bone grafting in patients with ONFH, surgically treated following Urbaniak's technique. © 2015 Wiley Periodicals, Inc. Microsurgery 36:573-577, 2016.

An ultrasound-guided technique for axillary brachial plexus nerve block in rabbits.

Regional anesthesia techniques, such as nerve blocks, are routinely used in humans and can contribute to multimodal approaches to pain management in research animals. Ultrasound guidance is an emerging aspect of regional anesthesia that has the potential to optimize local delivery and distribution of anesthetic agents, thereby reducing the amounts of these agents that must be administered. The authors developed an ultrasound-guided technique for effective block of the axillary brachial plexus in rabbits. They used this technique to carry out nerve block in 14 rabbits. The procedure was accomplished in a relatively short amount of time and achieved successful nerve block in all rabbits with no adverse effects. Sonographic visualization of the distribution of the local anesthetic ropivacaine led to administration of smaller anesthetic doses in eight of the rabbits without affecting the duration of nerve block. The authors conclude that their technique is feasible and safe and provides effective analgesia of the thoracic limb in rabbits. They recommend that this technique be integrated into multimodal approaches to pain management in rabbits undergoing thoracic limb surgery.

Severe Sprengel deformity associated with Klippel-Feil syndrome and a complex vascular abnormality that determined the corrective surgery technique.

Sprengel deformity (SD), a congenital condition characterized by elevation of the scapula, is a cause of functional and aesthetic defects that can be improved by surgical correction. Many cases of SD are associated with Klippel-Feil syndrome (KFS), in which there may be abnormalities of the supra-aortic vessels. We present the case of an 11-year-old girl with severe SD and KFS. The left vertebral artery arose from the subclavian artery in a very high cervical location, which made surgical descent of the scapula unfeasible. The patient was treated using a Mears procedure, with osteotomy of the scapula and tenotomy of the long head of the triceps. The appearance and range of motion of the shoulders improved considerably, and there were no vascular complications. A morphologic vascular assessment is essential in children with SD and concomitant KFS to avoid potentially serious iatrogenic vascular injury when performing a scapular-descending surgical technique.

The role of subscapularis muscle denervation in the pathogenesis of shoulder internal rotation contracture after neonatal brachial plexus palsy: a study in a rat model.

We assessed the role of subscapularis muscle denervation in the development of shoulder internal rotation contracture in neonatal brachial plexus injury. Seventeen newborn rats underwent selective denervation of the subscapular muscle. The rats were evaluated at weekly intervals to measure passive shoulder external rotation. After 4 weeks, the animals were euthanized. The subscapularis thickness was measured using 7.2T MRI axial images. The subscapularis muscle was then studied grossly, and its mass was registered. The fiber area and the area of fibrosis were measured using collagen-I inmunostained muscle sections. Significant progressive decrease in passive shoulder external rotation was noted with a mean loss of 58° at four weeks. A significant decrease in thickness and mass of the subscapularis muscles in the involved shoulders was also found with a mean loss of 69%. Subscapularis muscle fiber size decreased significantly, while the area of fibrosis remained unchanged. Our study shows that subscapularis denervation, per se, could explain shoulder contracture after neonatal brachial plexus injury, though its relevance compared to other pathogenic factors needs further investigation.

The role of muscle imbalance in the pathogenesis of shoulder contracture after neonatal brachial plexus palsy: a study in a rat model.

BACKGROUND: An internal rotation contracture of the shoulder is common after neonatal brachial plexus injuries due to subscapularis shortening and atrophy. It has been explained by 2 theories: muscle denervation and muscle imbalance between the internal and external rotators of the shoulder. The goal of this study was to test the hypothesis that muscle imbalance alone could cause subscapularis changes and shoulder contracture. MATERIALS AND METHODS: We performed selective neurectomy of the suprascapular nerve in 15 newborn rats to denervate only the supraspinatus and the infraspinatus muscles, leaving the subscapularis muscle intact. After 4 weeks, passive shoulder external rotation was measured and a 7.2-T magnetic resonance imaging scan of the shoulders was used to determine changes in the infraspinatus and subscapularis muscles. The subscapularis muscle was weighed to determine the degree of mass loss. An additional group of 10 newborn rats was evaluated to determine the sectional muscle fiber size and muscle area of fibrosis by use of images from type I collagen immunostaining. RESULTS: There was a significant decrease in passive shoulder external rotation, with a mean loss of 66°; in the thickness of the denervated infraspinatus, with a mean loss of 40%; and in the thickness and weight of the non-denervated subscapularis, with mean losses of 28% and 25%, respectively. No differences were found in subscapularis muscle fiber size and area of fibrosis between shoulders after suprascapular nerve injury. CONCLUSIONS: Our study supports the theory that shoulder muscle imbalance is a cause of shoulder contracture in patients with neonatal brachial plexus palsy.

Single-Access Fetal Endoscopy (SAFE) for myelomeningocele in sheep model I: amniotic carbon dioxide gas approach.

BACKGROUND: This study aimed to assess the feasibility of single-access fetal endoscopy (SAFE) for the management of myelomeningocele (MMC) using intrauterine carbon dioxide as a distension medium in a sheep model. METHODS: This prospective experimental case-control study investigated 12 lamb fetuses that had a myelomeningocele-like defect surgically created on the 75th day of gestation. Four fetuses remained untreated (control group), and eight fetuses had MMC repair using two fetoscopic approaches with carbon dioxide used to distend the amniotic cavity. A collagen patch was placed over the defect and secured with surgical sealant. Four animals had a two-port fetoscopic procedure, and four animals had SAFE. Clinical and pathologic studies were performed after delivery. RESULTS: This study confirmed the validity of the animal MMC model. None of the control animals was able to stand or walk, and all had a significant defect in the lumbar area with continuous leakage of cerebrospinal fluid, ventriculomegaly, and a Chiari-II malformation. All the treated animals, independently of the number of ports used in the repair, were able to walk and had a closed defect with resolution of the Chiari malformation. CONCLUSIONS: The SAFE patch and glue coverage of surgically created fetal MMC is feasible and effective in restoring gross neurologic function in the fetal lamb model.

Muscular and glenohumeral changes in the shoulder after brachial plexus birth palsy: an MRI study in a rat model.

BACKGROUND: Shoulder abnormalities are the major cause of morbidity in upper brachial plexus birth palsy (BPBP). We developed a rat model of upper trunk BPBP and compared our findings to previously reported animal models and to clinical findings in humans. METHODS: Forty-three 5-day-old newborn rats underwent selective upper trunk neurectomy of the right brachial plexus and were studied 3 to 20 weeks after surgery. The passive shoulder external rotation was measured and the shoulder joint was assessed bilaterally by a 7.2T MRI bilaterally. RESULTS: We found a marked decrease in passive shoulder external rotation, associated with a severe subscapularis muscle atrophy and contracture. None however developed the typical pattern of glenohumeral dysplasia. CONCLUSIONS: In contradiction with previous reports, our study shows that the rat model is not adequate for preclinical studies of shoulder dysplasia. However, it might serve as a useful model for studies analyzing shoulder contracture occurring after upper BPBP.

Maldevelopment of the cerebral cortex in the surgically induced model of myelomeningocele: implications for fetal neurosurgery.

PURPOSE: The purpose of this study is to describe the malformations of cortical development detected in a model of cerebrospinal fluid (CSF) leakage and the influence of surgical closure technique on developmental outcome. METHODS: Using a surgically induced model of myelomeningocele (MMC) in sheep, we studied the effects of different repair methods upon the development of hydrocephalus, the presence of the Arnold-Chiari II (AC-II) hindbrain malformation, and cerebral cortex developmental anomalies using gross and histologic (hematoxylin and eosin and Nissl staining) study techniques. RESULTS: A malformed cerebral cortex, including 2 anomalous cortical folding patterns, and lower brain weights were observed in the untreated animals. Hydrocephalus and AC-II malformations were also found in this group. These malformations were mostly prevented with prenatal 2-layer closure. CONCLUSIONS: Cerebral cortical malformations and hydrocephalus, in addition to the AC-II hindbrain malformation, are disorders caused by fetal CSF leakage. These malformations were prevented with the technique of MMC closure currently used in humans. Both observations magnify the importance of the second hit associated with chronic CSF leakage, in addition to the primary defect causing the MMC, in the development of the malformation complex.

Fetoscopic coverage of experimental myelomeningocele in sheep using a patch with surgical sealant.

OBJECTIVE: Assess the feasibility of a fetoscopic patch coverage method for myelomeningocele repair in a sheep model. STUDY DESIGN: Experimental study. A myelomeningocele-like defect was created in 15 fetal sheep on day 75 of gestation. Six remained untreated, whereas 9 underwent fetoscopic coverage of the defect on day 95 of gestation using an inert patch secured with surgical sealant. Clinical and histological examinations were performed after delivery. RESULTS: Four valid newborn lambs were obtained in each group. Mean fetoscopic surgical time was 26.9 (SD=7.4)min. All untreated animals had an open lumbar defect with cerebrospinal fluid leakage, paraplegia, urinary incontinence, and Chiari malformation. All treated animals had a closed defect and were able to walk; one had weak bladder control, and another mild Chiari malformation. CONCLUSION: In a chronic myelomeningocele model in fetal sheep, fetoscopic repair using a sealed patch results in simple, fast, satisfactory neural tube closure and averts neurological damage and Chiari malformation.

Effects of birth advancement in Chiari malformation in a surgical myelomeningocele model in rabbits.

BACKGROUND/PURPOSE: In myelomeningocele (MMC), Chiari II malformation progresses during gestation because of the continuous loss of cerebrospinal fluid at the site of the defect. Our purpose was to assess the impact of birth advancement (BA) and prenatal corticosteroid treatment (PCT) on Chiari malformation in a surgical MMC model in rabbits. METHODS: A surgical MMC-like defect was created in 75 fetal rabbits. Animals were distributed into 4 groups depending on the treatment received: not treated and those undergoing BA + PCT, BA, or PCT. The degree of Chiari malformation in newborn rabbits was defined as the percentage of downward protrusion of the hindbrain between the end of the occipital bone and the beginning of the first vertebral arch. RESULTS: The degree of hindbrain herniation was 80% (8.15) in the not treated group, 36.8% (10.57) in BA + PCT, 41.8% (8.27) in BA, and 44.4% (8.32) in PCT. The BA + PCT, BA, and PCT groups showed less severe hindbrain herniation than not treated animals (mean decrease, 39.86%; SD, 10.57; P = .000). There were no significant differences between the BA + PCT, BA, and PCT groups (P = .311). CONCLUSIONS: Birth advancement and prenatal administration of corticosteroids decrease the severity of the hindbrain herniation component of Chiari II malformation in surgical MMC in fetal rabbits.

Inert patch with bioadhesive for gentle fetal surgery of myelomeningocele in a sheep model.

OBJECTIVE: Current techniques used in foetal myelomeningocele repair can require considerable manipulation of fragile foetal tissues to obtain tension-free closure. The aim of this study was to assess the feasibility of a simple foetal coverage method without foetal tissue manipulation to provide closure of the neural tube defect in myelomeningocele. STUDY DESIGN: This is an experimental study performed in 15 foetal sheep with lumbar myelomeningocele, surgically created on day 75 of gestation. Five foetuses remained untreated. Ten underwent coverage with inert sheeting (5 Silastic; 5 Silastic+Marlex) secured by surgical tissue adhesive without suturing on day 95; none of them underwent foetal muscle or skin manipulation. Clinical and subsequent histological examinations were performed at 48h after birth. The Chi-square, Fisher exact, and Mann-Whitney U tests, when appropriate, were used for the comparisons. RESULTS: The mean operating time for foetal coverage was 7.1 (SD=1.6)min. All untreated animals were unable to walk, had sphincter incontinence, showed an open defect, histological spinal cord damage, and a large Chiari malformation. All covered animals were able to walk, had sphincter continence, showed almost complete closure of the defect with regeneration of several soft tissue layers, and minimum Chiari malformation. CONCLUSION: In a surgical myelomeningocele model in sheep, a simple, fast and gentle coverage method using a sealed patch avoids foetal tissue manipulation and enables adequate closure of the neural tube defect, providing regeneration of several tissue layers that protect the spinal cord, and significantly reducing Chiari II malformation.

Fetoscopic release of extremity amniotic bands with risk of amputation.

With the advent of less-invasive fetal surgery techniques, nonlethal disorders are considered amenable to intrauterine treatment. Extremity amniotic band syndrome fulfils the criteria of intrauterine disorders conformable with fetal treatment: capability of prenatal diagnosis and severity. We report 2 cases of extremity amniotic bands with risk of limb amputation released fetoscopically with YAG laser.