Collagenase treatment decreases muscle stiffness in cerebral palsy: A preclinical ex vivo biomechanical analysis of hip adductor muscle fiber bundles.

AIM: To determine the dose-response relationship of collagenase Clostridium histolyticum (CCH) on collagen content and the change in muscle fiber bundle stiffness after ex vivo treatment of adductor longus biopsies with CCH in children with cerebral palsy (CP). METHOD: Biopsy samples of adductor longus from children with CP (classified in Gross Motor Function Classification System levels IV and V) were treated with 0 U/mL, 200 U/mL, 350 U/mL, or 500 U/mL CCH; percentage collagen reduction was measured to determine the dose-response. Peak and steady-state stresses were determined at 1%, 2.5%, 5%, and 7.5% strain increments; Young's modulus was calculated. RESULTS: Eleven patients were enrolled (nine males, two females, mean age at surgery 6 years 5 months; range: 2-16 years). A linear CCH dose-response relationship was determined. Peak and steady-state stress generation increased linearly at 5.9/2.3mN/mm2 , 12.4/5.3mN/mm2 , 22.2/9.7mN/mm2 , and 33.3/15.5mN/mm2 at each percentage strain increment respectively. After CCH treatment, peak and steady-state stress generation decreased to 3.2/1.2mN/mm2 , 6.5/2.9mN/mm2 , 12.2/5.7mN/mm2 , and 15.4/7.7mN/mm2 respectively (p < 0.004). Young's modulus decreased from 205 kPa to 100 kPa after CCH (p = 0.003). INTERPRETATION: This preclinical ex vivo study provides proof of concept for the use of collagenase to decrease muscle stiffness in individuals with CP.

What is the best treatment for a child with an acute tear of the anterior cruciate ligament?

With the heightened popularity of childhood sporting activity, the number of paediatric anterior cruciate ligament (ACL) ruptures has increased. Management of these injuries presents a particular challenge due to the open femoral and tibial growth plates. Physeal damage has the potential to cause angular deformity or length discrepancy. This review was conducted to determine the best way to treat this injury. A primary search of Ovid MEDLINE (1 October 2017) used the terms: (ACL or anterior cruciate ligament) and (young or child or children or pediatric or immature or pre-pubescent). Titles/Abstracts of 369 articles were screened for relevance. A total of 217 were excluded, leaving 152 articles for full-paper retrieval. Of these, 9 articles remained with one further article identified during cross-referencing; 10 papers (1 level 2 and 9 level 3) were included for analysis. Comparative studies investigating surgical (140 knees) versus conservative (110 knees) treatment provide evidence in favour of the former, in reducing instability and meniscal tears and improving return to previous activity. Of the papers analysed (163 reconstructions), there was only one case of growth arrest (0.6%) and no cases of length discrepancy. In those studies investigating early (218 patients) versus delayed (140 patients) reconstruction, medial meniscal tears and chondral injuries occurred more frequently in the delayed group. To conclude, for children, there is level 2/3 evidence that early operative ACL reconstruction offers the best chance of a return to pre-injury sporting activity and minimises the risks of further structural damage. Iatrogenic growth disturbance remains a rare but worrying complication.

Evidence-based Pediatric Orthopaedics: How Safe is "Safe"?

BACKGROUND: The aim of minimizing the risks of complications and adverse events is at the center of surgical practice.This study aimed to assess the evidence on which pediatric orthopaedic surgical procedures are described as "safe." In particular, the objective was to ascertain the proportion of studies describing a procedure as "safe," which achieved a 95% upper limit confidence interval of risk of 5% or less for major adverse events. METHOD: A primary search of Journal of Paediatric Orthopaedics 2009 to 2014 for the single term "safe" returned 71 papers appropriate for analysis. Of these, 60 positively identified at least 1 intervention as "safe." These papers were analyzed and the number of interventions and the number of complications recorded. Data sets (n=67) were created and the 95% upper confidence interval calculated for the probability of a complication. RESULTS: Only 16 data sets (ex 67) provided evidence that the probability of a major complication was under 5%. CONCLUSIONS: This work suggests there is widespread failure of understanding of how low sample sizes or can lead to an unjustifiable claim that procedures are "safe." LEVEL OF EVIDENCE: Unclassifiable.

Introduction of a simple guideline to improve neurological assessment in paediatric patients presenting with upper limb fractures.

BACKGROUND: Neurological examination in children presenting with upper limb fractures is often poorly performed in the Emergency Department (ED). We aimed to assess the improvement in documented neurological examination for children presenting with upper limb fractures following introduction of a simple guideline. METHODS: We developed and introduced a simple guideline for upper limb neurological assessment in children ('rock, paper, scissors, OK'). We compared documentation of neurological examination and nerve injury detection at our hospital before and after introduction of this guideline, as well as for children admitted from external hospitals (where the guideline had not been introduced). RESULTS: In the period following guideline introduction, 97 children with upper limb fractures were admitted (46% presenting directly to our ED and 54% admitted from external hospitals). This cohort was similar in number and distribution to the cohort reviewed prior to the guideline. Documentation of neurological examination in our ED increased from 92% to 98% after guideline introduction. Documented information on nerves examined also increased from 2% to 68% (p<0.01). Prior to the guideline, there were six nerve injuries, all of which were missed in our ED. After guideline introduction, there were four nerve injuries, all of which were detected in our ED. Documentation and nerve injury detection at external hospitals over the same time period showed no improvement. CONCLUSIONS: A simple guideline to assist neurological examination in children with upper limb fractures can significantly improve the quality of documented neurological assessment and nerve injury detection.

Integrative "omic" analysis of experimental bacteremia identifies a metabolic signature that distinguishes human sepsis from systemic inflammatory response syndromes.

RATIONALE: Sepsis is a leading cause of morbidity and mortality. Currently, early diagnosis and the progression of the disease are difficult to make. The integration of metabolomic and transcriptomic data in a primate model of sepsis may provide a novel molecular signature of clinical sepsis. OBJECTIVES: To develop a biomarker panel to characterize sepsis in primates and ascertain its relevance to early diagnosis and progression of human sepsis. METHODS: Intravenous inoculation of Macaca fascicularis with Escherichia coli produced mild to severe sepsis, lung injury, and death. Plasma samples were obtained before and after 1, 3, and 5 days of E. coli challenge and at the time of killing. At necropsy, blood, lung, kidney, and spleen samples were collected. An integrative analysis of the metabolomic and transcriptomic datasets was performed to identify a panel of sepsis biomarkers. MEASUREMENTS AND MAIN RESULTS: The extent of E. coli invasion, respiratory distress, lethargy, and mortality was dependent on the bacterial dose. Metabolomic and transcriptomic changes characterized severe infections and death, and indicated impaired mitochondrial, peroxisomal, and liver functions. Analysis of the pulmonary transcriptome and plasma metabolome suggested impaired fatty acid catabolism regulated by peroxisome-proliferator activated receptor signaling. A representative four-metabolite model effectively diagnosed sepsis in primates (area under the curve, 0.966) and in two human sepsis cohorts (area under the curve, 0.78 and 0.82). CONCLUSIONS: A model of sepsis based on reciprocal metabolomic and transcriptomic data was developed in primates and validated in two human patient cohorts. It is anticipated that the identified parameters will facilitate early diagnosis and management of sepsis.

Photographic recording of the features of the Pirani classification for club feet--a case study.

Club foot is a common congenital abnormality, and a complex deformity. In the past twenty years, the deformity has been better classified by considering the different components of deformity. The Pirani scoring system is widely used--and analogous standardised photographic views can be used to document this condition and its progress. Here I describe four views that aid in deformity assessment, correlating to component deformities assessed in the Pirani score.

Diagnosing and managing hip problems in childhood.

The hip and proximate tissues are implicated in a variety of childhood conditions, and in the differential diagnosis of many more. To a large extent the possible diagnoses are limited by the child's age, an accurate history and thorough examination. Developmental dysplasia of the hip (DDH) is a spectrum disorder of joint development and/or instability. It is a major cause of morbidity in children and adults. It can be classified into three types: neuromuscular; teratological; and idiopathic (the most common type). Examination of the hips is carried out neonatally using Ortolani and Barlow manoeuvres to look for dislocation. These tests have high sensitivity but low specificity, and this is one reason why DDH is still picked up late. When a limping child presents it is important that the less common diagnoses, including infection, neoplasia and slipped femoral epiphysis are kept in mind and urgent referral made if necessary. In one study, where a diagnosis was made, the hip joint was the culprit in the majority of cases. Of these, 40% were diagnosed as irritable hip or transient synovitis. Other inflammatory arthritides/tendinoses accounted for 3.2%, Perthes' disease 2%, and infection 3.6%. Any age group is vulnerable to infection such as septic arthritis, osteomyelitis and pelvic pyomyositis. Early diagnosis and treatment, comprising antibiotics with or without surgery, is critical. In the limping child, fever with focal tenderness or restricted range of movement is indicative of infection unless investigations show otherwise.

Optimising the management of congenital talipes.

Congenital talipes equinovarus (CTEV) is a condition of the lower limb in which there is fixed structural cavus, forefoot adductus, hindfoot varus and ankle equinus. In Caucasian populations the incidence is around 1.2 per 1,000 live births, with a male to female ratio of 2.25:1. The left and right feet are equally commonly affected, and 50% of cases are bilateral. It is important to differentiate CTEV from a non-structural or positional talipes which is fully correctable. This positional variant occurs about five times as commonly as CTEV. The latter condition does not require casting or surgical treatment. The majority of CTEV cases are picked up at the early baby check or on prenatal ultrasound, and referred to the paediatric orthopaedic service. However, some cases are mistaken early on as the positional variant, and may therefore present to the GP e.g. at the six week check. Urgent referral is warranted as the Ponseti treatment should be started early. The feet must be examined directly to see if the components of the deformity are fixed, defining CTEV. The hips (stability, length equivalence, range and symmetry of abduction) and spine (in particular looking for peripheral stigmata of spina bifida) must also be examined. Most cases of CTEV occur in isolation i.e. without other anomalies. However, a proportion are syndromic. In a recent study of patients with fixed CTEV, 27.7% had a syndromal cause. Over the past 25 years there has been a dramatic shift away from extensive surgical releases to manipulative methods/serial casting such as the Ponseti technique. The technique involves a series of manipulations and casts, usually on a weekly basis, in which the foot is brought round to a corrected position. The boots and bar splintage is a vital part of the Ponseti technique and relapse is strongly correlated with non-compliance.

The thin red line.

This sonnet is a brief symbolic meditation on the brevity of life and the "thin red line": by turns blood (stream/supply and life-giving), a boundary to be crossed (the Rubicon), the limit of our medical (and surgical) endeavors, and finally our horizon. "The thin red line" is also a metaphor for resistance, attributed in part to Kipling's poem Tommy: in particular to resilience by the few, against ostensibly superior forces. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Rapid prototyping in orthopaedic surgery: a user's guide.

Rapid prototyping (RP) is applicable to orthopaedic problems involving three dimensions, particularly fractures, deformities, and reconstruction. In the past, RP has been hampered by cost and difficulties accessing the appropriate expertise. Here we outline the history of rapid prototyping and furthermore a process using open-source software to produce a high fidelity physical model from CT data. This greatly mitigates the expense associated with the technique, allowing surgeons to produce precise models for preoperative planning and procedure rehearsal. We describe the method with an illustrative case.

Foot anomalies and proximal symphalangism.

We report the case of a 2-week-old girl born at term (by vaginal delivery and without antenatal or perinatal events) who was referred as having "bilateral talipes and bilateral proximal symphalangism of little and ring fingers." The "talipes" was atypical with marked equinus and varus, but no cavus or adductus of the midfoot. Her mother had both symphalangism (absence of proximal interphalangeal joints) of middle, ring, and little fingers bilaterally and fixed pes planus with a rigid fixed hindfoot-and these deformities had also been present from birth. The maternal grandmother was similarly affected. However, the neonatal subject has an unaffected older sibling; maternal siblings are also unaffected. The three affected people did not have other obvious musculoskeletal abnormalities. Because of the coalitions, the child's atypical talipes was managed by a modified Kite's procedure. Symphalangism-coalition syndromes may be associated with conductive deafness because of fusion of the auditory ossicles.

Revisional surgery for hallux valgus with serial osteotomies at two levels.

The aetiology and form of hallux valgus (HV) is varied with many corrective procedures described. We report a 39-year-old woman, previously treated with a Chevron osteotomy, who presented with recurrent right HV, metatarsus primus varus, and associated bunion. Osteotomies were performed at two levels as a revisional procedure. This report highlights (1) limitations of the Chevron osteotomy and (2) the revisional procedure of the two level osteotomies: (i) proximal opening-wedge basal osteotomy and (ii) distal short Scarf with medial closing wedges. If a Chevron osteotomy is used inappropriately, for example, in an attempt to correct too large a deformity, it may angulate laterally causing a malunion with an increased distal metatarsal articular angle. Secondly, it is feasible to correct this combined deformity using a combination of proximal opening-wedge and distal short Scarf osteotomies.

Profiles of biomarkers of excess alcohol consumption in patients undergoing total hip replacement: correlation with function.

AIMS: Patients who misuse alcohol may be at increased risk of surgical complications and poorer function following hip replacement. Identification and intervention may lead to harm reduction and improve the outcomes of surgery. The aim of this study was to determine the prevalence of biomarker elevation in patients undergoing hip replacement and to investigate any correlation with functional scores and complications. METHODS: We performed a retrospective study that examined the profile of biomarkers of alcohol misuse in 1049 patients undergoing hip replacement. Results. Gamma-glutamyltransferase was elevated in 150 (17.6%), and mean corpuscular volume was elevated in 23 (4%). At one year general physical health was poorer where there was elevation of γGT, and the mental health and hip function was poorer with elevation of MCV. There were no differences in complications. DISCUSSION: Raised biomarkers can alert clinicians to potential problems. They also provide an opportunity to perform further investigation and offer intervention. Future research should focus on the use in orthopaedic practice of validated screening questionnaires and more sensitive biomarkers of alcohol misuse. CONCLUSION: This study demonstrates a potential substantial proportion of unrecognised alcohol misuse that is associated with poorer functional scores in patients after total hip replacement.

Swelling around a child's knee.

Swellings around the paediatric knee have a large differential diagnosis, although the majority can be diagnosed clinically. Some swellings merit further investigation by Magnetic Resonance Imaging (MRI).

A 45-year-old man presenting with anterior compartment syndrome three weeks following conservative treatment of an Achilles tendon rupture.

Compartment syndrome complicating a ruptured Achilles tendon has previously been reported in a surgically treated patient. However--to our knowledge--this is the first report of compartment syndrome following conservative treatment. A 45-year-old man ruptured his Achilles tendon and elected to have treatment in an equinus cast. Three weeks later, he developed compartment syndrome and despite fasciotomy, required surgical debridement of his anterior compartment. Delay in both diagnosis and subsequent fasciotomy resulted in a poor outcome. Any suspicion of compartment syndrome mandates early compartmental pressure monitoring. The exact aetiology is uncertain but we speculate that the equinus position of his ankle combined with weight-bearing, was a major contributing factor.

Meiosis-specific gene discovery in plants: RNA-Seq applied to isolated Arabidopsis male meiocytes.

BACKGROUND: Meiosis is a critical process in the reproduction and life cycle of flowering plants in which homologous chromosomes pair, synapse, recombine and segregate. Understanding meiosis will not only advance our knowledge of the mechanisms of genetic recombination, but also has substantial applications in crop improvement. Despite the tremendous progress in the past decade in other model organisms (e.g., Saccharomyces cerevisiae and Drosophila melanogaster), the global identification of meiotic genes in flowering plants has remained a challenge due to the lack of efficient methods to collect pure meiocytes for analyzing the temporal and spatial gene expression patterns during meiosis, and for the sensitive identification and quantitation of novel genes. RESULTS: A high-throughput approach to identify meiosis-specific genes by combining isolated meiocytes, RNA-Seq, bioinformatic and statistical analysis pipelines was developed. By analyzing the studied genes that have a meiosis function, a pipeline for identifying meiosis-specific genes has been defined. More than 1,000 genes that are specifically or preferentially expressed in meiocytes have been identified as candidate meiosis-specific genes. A group of 55 genes that have mitochondrial genome origins and a significant number of transposable element (TE) genes (1,036) were also found to have up-regulated expression levels in meiocytes. CONCLUSION: These findings advance our understanding of meiotic genes, gene expression and regulation, especially the transcript profiles of MGI genes and TE genes, and provide a framework for functional analysis of genes in meiosis.

Increasing the osmolarity of joint irrigation solutions may avoid injury to cartilage: a pilot study.

Saline (0.9%, 285 mOsm) and Hartmann's solution (255 mOsm) are two commonly used joint irrigation solutions that alter the extracellular osmolarity of in situ chondrocytes during articular surgery. We asked whether varying the osmolarity of these solutions influences in situ chondrocyte death in mechanically injured articular cartilage. We initially exposed osteochondral tissue harvested from the metacarpophalangeal joints of 3-year-old cows to solutions of 0.9% saline and Hartmann's solution of different osmolarity (100-600 mOsm) for 2 minutes to allow in situ chondrocytes to respond to the altered osmotic environment. The full thickness of articular cartilage then was "injured" with a fresh scalpel. Using confocal laser scanning microscopy, in situ chondrocyte death at the injured cartilage edge was quantified spatially as a function of osmolarity at 2.5 hours. Increasing the osmolarity of 0.9% saline and Hartmann's solution to 600 mOsm decreased in situ chondrocyte death in the superficial zone of injured cartilage. Compared with 0.9% saline, Hartmann's solution was associated with greater chondrocyte death in the superficial zone of injured cartilage, but not when the osmolarity of both solutions was increased to 600 mOsm. These experiments may have implications for the design of irrigation solutions used during arthroscopic and open articular surgery.

Epidemiology of Irritable Hip in Western Scotland: A Follow-Up Study.

Background A 'limping child' commonly presents to the emergency department (ED). In the absence of trauma, many are diagnosed with irritable hip (IH). The aetiology of IH is not well understood and there may be geographical and seasonal variations. We previously established one year (2016) epidemiological data of IH presenting to the Royal Hospital for Children (RHCG) ED in Glasgow, Scotland. The sentinel findings in that year were (i) an age distribution shift to younger (peak at two years of age), (ii) no marked association with social class, and (iii) a spring preponderance. We sought to strengthen or refute these findings by repeating our study to obtain comparative data for 2017. Methods We performed a retrospective analysis of all children discharged from the RHCG ED from January to December 2017. Relevant discharge codes were determined, and patient records screened. Patients without a discharge code had their presenting complaint and medical record screened. These data were compared to that of the previously published study from the same ED (2016). Results Several findings were consistent with the conclusions of the 2016 study. The incidence was similar with 362 and 354 cases diagnosed in 2017 and 2016 respectively. The boy-girl ratio was consistent across both data-sets, 2:1 and 1.9:1 respectively. The mean age of presentation was similar (3.3 vs 3.5 years) across both years, with the same medians (three years) and peaks (two years). There was no overt difference in incidence or correlation to social deprivation. However, in 2016, a spring preponderance was seen whereas there was an autumn preponderance in 2017. Pooling data from the two cohorts, 93% (n=668) of patients were managed exclusively by ED physicians, with 70% (n=504) not requiring any further follow-up. The majority of patients who required follow-up were seen in ED clinics (169/212, 79.7%). No patient initially diagnosed as IH was found to have septic arthritis (SA). Conclusion In this follow-up study, we again found (i) a younger age profile than other studies, and (ii) no overt association with social deprivation. The major difference between the previous (2016) and current (2017) study was the apparent seasonal peaks: spring (2016), and autumn (2017). This difference does not negate the 'antecedent infection' hypothesis, but any aetiological proposal should be capable of accounting for this discrepancy. Additionally, our studies highlight that the majority of these patients can be managed in the ED alone.

Evolution of the opossum major histocompatibility complex: evidence for diverse alternative splice patterns and low polymorphism among class I genes.

The opossum major histocompatibility complex (MHC) shares a similar organization with that of non-mammals while containing a diverse set of class I genes more like that of eutherian (placental) mammals. There are 11 class I loci in the opossum MHC region, seven of which are known to be transcribed. The previously described Monodelphis domestica (Modo)-UA1 and Modo-UG display characteristics consistent with their being classical and non-classical class I genes, respectively. Here we describe the characteristics of the remaining five transcribed class I loci (Modo-UE, -UK, -UI, -UJ and -UM). All five genes have peptide-binding grooves with low or no polymorphism, contain unpaired cysteines with the potential to produce homodimer formation and display genomic organizational features that would be unusual for classical class I loci. In addition, Modo-UJ and -UM were expressed in alternatively spliced mRNA forms, including a potentially soluble isoform of Modo-UJ. Thus, the MHC region of the opossum contains a single class I gene that is clearly classical and six other class I genes each with its own unique characteristics that probably perform roles other than or in addition to antigen presentation.