Hyperthermia elevates brain temperature and improves behavioural signs in animal models of autism spectrum disorder.

BACKGROUND: Autism spectrum disorders (ASD) are predominantly neurodevelopmental and largely genetically determined. However, there are human data supporting the idea that fever can improve symptoms in some individuals, but those data are limited and there are almost no data to support this from animal models. We aimed to test the hypothesis that elevated body temperature would improve function in two animal models of ASD. METHODS: We used a 4 h whole-body hyperthermia (WBH) protocol and, separately, systemic inflammation induced by bacterial endotoxin (LPS) at 250 µg/kg, to dissociate temperature and inflammatory elements of fever in two ASD animal models: C58/J and Shank3B- mice. We used one- or two-way ANOVA and t-tests with normally distributed data and Kruskal-Wallis or Mann-Whitney with nonparametric data. Post hoc comparisons were made with a level of significance set at p < 0.05. For correlation analyses, data were adjusted by a linear regression model. RESULTS: Only LPS induced inflammatory signatures in the brain while only WBH produced fever-range hyperthermia. WBH reduced repetitive behaviours and improved social interaction in C58/J mice and significantly reduced compulsive grooming in Shank3B- mice. LPS significantly suppressed most activities over 5-48 h. LIMITATIONS: We show behavioural, cellular and molecular changes, but provide no specific mechanistic explanation for the observed behavioural improvements. CONCLUSIONS: The data are the first, to our knowledge, to demonstrate that elevated body temperature can improve behavioural signs in 2 distinct ASD models. Given the developmental nature of ASD, evidence that symptoms may be improved by environmental perturbations indicates possibilities for improving function in these individuals. Since experimental hyperthermia in patients would carry significant risks, it is now essential to pursue molecular mechanisms through which hyperthermia might bring about the observed benefits.

Effectiveness of an Antibiotic-impregnated Bioabsorbable Carrier for the Treatment of Chronic Intramedullary and Diffuse Osteomyelitis.

Aim: The surgical management of chronic intramedullary osteomyelitis involves debridement of affected non-viable tissue and the use of antibiotics. Where surgery leaves a cavity, dead-space management is often through antibiotic-impregnated bone cement. These depots of local antibiotics are variable in elution properties and need removal. We review our unit's experience using a bioabsorbable synthetic calcium sulphate to deliver gentamicin as an adjunct in the treatment of osteomyelitis involving the medullary canal. Materials and methods: We retrospectively reviewed 34 patients with chronic osteomyelitis who were treated using this method in our institute. Variables recorded included aetiology, previous interventions, diagnostic criteria, radiological features, serology, and microbiology. The Cierny-Mader system was used to classify. Follow-up involved a survival analysis to time to recurrence, clinical and functional assessment (AOFAS-Ankle/IOWA knee/Oxford Hip/DASH scores) and a general health outcome questionnaire (SF36). The primary outcome measure was clinical recurrence of infection. Results: There were 24 male and 10 female patients. The mean age at presentation was 47 years (20-67). Clinical, laboratory, radiological, and patient reported outcomes were obtained at a median follow-up of 2.5 years (1.4-6.6 years). The bones involved were the femur (14, 41%), tibia (16, 47%), radius (1, 3%), and humerus (3, 9%). There were 13 cases classified as Cierny-Mader stage IV (diffuse with intramedullary osteomyelitis) and 21 cases as Cierny-Mader stage I. The median Oxford Hip score was 38 (11 patients, range 9-48). The median AOFAS score was 78 (14 patients, range 23-100). The median IOWA knee score was 71 (25 patients, range 22-95). The median DASH score was 33 (2 patients, range 1.7-64.2). There were two recurrences. The treatment success to date is 94%. Conclusion: In our series of patients, bioabsorbable carriers of antibiotics appear to be effective adjuncts to surgical treatment of osteomyelitis and were associated with high clinical success rates. How to cite this article: Selvaratnam V, Roche A, Narayan B, et al. Effectiveness of an Antibiotic-impregnated Bioabsorbable Carrier for the Treatment of Chronic Intramedullary and Diffuse Osteomyelitis. Strategies Trauma Limb Reconstr 2023;18(3):148-154.

What is the evidence for efficacy, effectiveness and safety of surgical interventions for plantar fasciopathy? A systematic review.

AIMS: To systematically review randomised control trials (RCT's) assessing the effectiveness and safety of surgical interventions in adults with plantar fasciopathy (PF). MATERIALS AND METHODS: We searched MEDLINE, EMBASE, Web of Science, Google Scholar, the Cochrane Central Register of Controlled Trials, trial registries and references lists. RCT's comparing surgical interventions with non-surgical or surgical comparisons in adults with PF were included. Primary outcomes were changes in first step pain severity/intensity, and incidence/nature of adverse events. Secondary outcomes included foot and ankle related disability/function, health related quality of life, cost effectiveness, changes in other reported measures of pain and medication use. Data were extracted at short-term (≤3 months post-intervention), medium-term (>3months-≤6 months post-intervention) or long-term (>6 months-≤2 years post-treatment). Certainty of evidence was evaluated using the modified Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: From 3620 screened records, we included 8 studies comprising 345 patients. Substantial variation across trials precluded meta-analysis, hence a narrative synthesis was conducted. We judged all studies to have high risk of bias. For all outcome comparisons our GRADE judgement for the certainty of the evidence was very low. Three studies compared one type of surgery with another largely showing little to no difference in outcomes for pain, function or quality of life. Five studies compared surgery with non-surgical interventions-three providing very low certainty evidence that surgery may improve pain and function at long-term follow-up compared to non-surgical comparisons, whereas two studies provided no long-term between-group differences. Reporting of adverse events were inadequate, inconsistent or absent across all studies. CONCLUSION: There is a paucity of high certainty evidence to support or refute the effectiveness and safety of surgical interventions in the management of PF. We make recommendations for improving the evidence base in this field.

Foot and ankle injuries related to the use of E-scooters - A case series and a review of literature.

INTRODUCTION: As E-scooter use is increasing with the introduction of urban rental schemes in the United Kingdom, associated foot and ankle injuries will become more prevalent. The aim of this study is to assess the injury pattern and injury severity of foot and ankle trauma associated with E-scooter use. METHODS: A retrospective case analysis of all E-scooter foot and ankle injuries presenting to three London hospitals between 1st January and 31st December 2020 was conducted. Data including demographics, mechanism and location of injury sustained, management, duration of hospital stay and mortality were collected. RESULTS: 20 patients were identified with a total of 27 foot and ankle fractures. Eight patients had fracture dislocations, four sustained open injuries and 45% (9/20) of patients required surgical treatment. Those travelling over 15.5 mph were significantly more likely to require operative intervention (70%) than those travelling below 15.5 mph (20%) (P < 0.033) and were more likely to have an open fracture (40% compared to 0%) (P < 0.0886), however the latter was not of statistical significance. 85% (17/20) of rider's injuries involved the foot and/or ankle only. There were no mortalities at 30 days. CONCLUSIONS: E-scooter use can cause serious foot and ankle injuries. Robust guidelines and legislation restricting top speeds and enforcing the wearing of protective clothing could be implemented. This may protect the E-scooter user from significant foot and ankle injury.

What is the evidence for efficacy, effectiveness and safety of surgical interventions for plantar fasciopathy? Protocol for a systematic review.

INTRODUCTION: Plantar fasciopathy (PF) is a degenerative condition of the plantar fascia, secondary to repetitive overloading. For the majority, PF is self-limiting with greater than 80% of those affected gaining complete resolution within 1 year. However, persistent symptoms develop in approximately 10% of cases. Clinical practice guidelines for first-line treatment of PF recommend conservative management. For people with persistent symptoms that have not resolved following a trial of 6-12 months of conservative management, surgery may be offered. However, to date there are no systematic reviews of the effectiveness of the various surgical procedures for PF. We aim to systematically review quantitative studies assessing the effectiveness of surgical interventions in the management of PF. METHODS AND ANALYSIS: We will search for all published and unpublished randomised clinical trials evaluating surgical interventions in the management of PF. Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE (OVID), EMBASE (OVID), Web of Science (ISI) and Google Scholar will be searched without restrictions on date or language of publication. Inclusion criteria will include people over 18 years, diagnosed by clinical examination with PF, or with an alternative diagnostic label (eg, plantar fasciitis, plantar heel pain, plantar fasciosis). The primary outcomes are changes in pain severity/intensity for first-step pain, and incidence and nature of adverse events. Secondary outcomes include foot and ankle-related disability/function, health-related quality of life, cost-effectiveness, changes in other reported measures of pain (eg, overall pain) and medication use. Outcomes will be assessed (1) short term (≤3 months after intervention), (2) medium term (>3 months to ≤6 months after intervention) or (3) long term (>6 months to ≤2 years after treatment). All data extraction will be performed by at least two independent reviewers on the basis of a priori developed extraction form. Where adequate data are found meta-analysis will be used to combine the results of studies for all core comparisons and outcomes using random effects models. Overall certainty of the evidence for each outcome will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: This systematic review does not require ethical approval as primary data will not be collected. The results of the study will be published in a peer-reviewed journal and presented at appropriate conferences. PROSPERO REGISTRATION NUMBER: CRD42019133563.

Return to Training and Playing After Acute Lisfranc Injuries in Elite Professional Soccer and Rugby Players.

BACKGROUND: Lisfranc joint injuries are increasingly recognized in elite soccer and rugby players. Currently, no evidence-based guidelines exist on time frames for return to training and competition after surgical treatment. PURPOSE: To assess the time to return to training and playing after Lisfranc joint injuries. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A consecutive series of 17 professional soccer and rugby players in the English Premier/Championship leagues was assessed using prospectively collected data. All were isolated injuries sustained during training or competitive matches. Each player had clinical and radiological evidence of an unstable Lisfranc injury and required surgical treatment. A standardized postoperative regimen was used. The minimum follow-up time was 2 years. RESULTS: Clinical and radiological follow-up was obtained in all 17 players. Seven players had primarily ligamentous injuries, and 10 had bony injuries. The time from injury to fixation ranged from 8 to 31 days, and hardware was removed at 16 weeks postoperatively. One athlete retired after a ligamentous injury; the remaining 16 players returned to training and full competition. Excluding the retired player, the mean time to return to training was 20.1 weeks (range, 18-24 weeks) and to full competition was 25.3 weeks (range, 21-31 weeks). There was a significant difference between the mean time to return to competition for rugby (27.8 weeks) and soccer players (24.1 weeks; P = .02) and for ligamentous (22.5 weeks) compared with bony injuries (26.9 weeks; P = .003). Three patients suffered deep peroneal nerve sensation loss, from which 1 patient did not fully recover. CONCLUSION: Return to competitive elite-level soccer and rugby is possible after surgically treated Lisfranc injuries. Return to training can take up to 24 weeks and return to playing up to 31 weeks, with bony injuries taking longer.

An atraumatic turf toe in an elite soccer player--a stress related phenomenon?

Plantar plate injuries to the hallux in elite athlete could potentially be career threatening. Reports in the literature are invariably linked to a significant traumatic episode. The occurrence of an atraumatic severe plantar plate injury in the presence of a bipartite sesamoid may suggest a stress related phenomenon. We present a case in an elite soccer player who was treated surgically and returned to top-level competition. The case is reported in detail and differences to other reports in the literature discussed.

Posterior ankle impingement in dancers and athletes.

The diagnosis of posterior ankle impingement requires an accurate history and specific examination. Computed tomography is a useful investigation to diagnose bony impingement, especially where plain radiography and/or magnetic resonance imaging are sometimes inconclusive. Accurate ultrasound-guided steroid/anesthetic injections are useful interventions to locate the symptomatic lesions and reduce symptoms and occasionally prove curative. If surgical debridement or excision is deemed necessary, arthroscopic surgery via a posterior approach is recommended to excise impingement lesions with a quicker return to sport expected and minimal complications. Open surgical excision, however, remains a viable treatment option.

Treatment and return to sport following a Jones fracture of the fifth metatarsal: a systematic review.

PURPOSE: The aim of this study is to better inform the sports surgeon of current evidence for the treatment of Jones fractures of the base of the 5th metatarsal. The study aimed to establish what the outcomes were for different treatments modalities. By doing this, the clinician will be better prepared to institute a logical, evidence-based approach to the treatment of their patients with this injury. METHODS: A thorough literature search was performed from 1980 to present day. Studies were included based on set criteria and analysed for their validity, and their results were scrutinised. Jones fractures were segregated into acute fractures, delayed unions and non-unions. RESULTS: Twenty-six studies were included, of which 22 were level 4 evidence, with only 1 randomised controlled trial. Functional outcome data were limited to return to sports in most studies with few studies using established scoring systems. Return to sports following intra-medullary screw fixation for acute fractures ranged from 4 to 18 weeks. Acute fractures treated non-operatively had a union rate of 76 % (pooled), whereas in fractures treated with a screw it was 96 % (pooled). Delayed unions treated non-operatively had a union rate of 44 and 97 % treated operatively. Non-unions treated with screw fixation healed in 97 % of cases. CONCLUSIONS: Although supported by mostly level 4 evidence, intra-medullary screw fixation is more likely to lead to successful union of all types of Jones fractures compared to non-operative treatments. Early return to play in athletes prior to full radiological union is not advised in case of re-fracture.

Lateral column lengthening osteotomies.

Lateral column lengthening procedures, either an Evans-type procedure or a calcaneocuboid distraction arthrodesis, clearly have a role to play in the management of a pes planovalgus foot deformity, as is evident from clinical outcome studies. Despite an abundance of literature intricately detailing the biomechanical effects of different operative procedures on the hindfoot, there is no clear consensus as to the best procedure or procedures to perform for a flexible pes planovalgus foot deformity. There is, therefore, no single solution to this problem; the surgeon must treat each patient as an individual and choose the procedure that will work best in their hands for any given foot pathology they are presented with. The surgeon must also be aware that to improve the kinematics of a planovalgus foot deformity, one may often have to perform multiple procedures and not a lateral column lengthening in isolation.

A hip resurfacing implant in an adolescent with cerebral palsy.

Pain or skin irritation due to the femoral stump after proximal femoral resection for chronic spastic hip dislocation in children with severe cerebral palsy may be encountered. We describe a technique that, to our knowledge, has been unreported earlier and can deal with this phenomenon to improve the patient's comfort level and help the patient to sit more comfortably.

Characterization of renal papillary antigen 1 (RPA-1), a biomarker of renal papillary necrosis.

Renal papillary necrosis (RPN) is a relatively common toxicity observed in preclinical drug safety testing. It is also observed in a variety of human diseases. RPN is difficult to diagnose without expensive scanning methods or histopathology. A noninvasive biomarker that could be detected at early stages of kidney damage would be of great value both to preclinical drug safety testing and in the clinic. An antibody raised to an unknown epitope of an antigen in rat kidney papilla was found to be specific for collecting duct cells in the kidney; this was termed renal papillary antigen 1 (RPA-1). In this study, the authors show that RPA-1 is an early biomarker of RPN in two different rat models of toxicity: 2-bromoethanamine (BEA) and N-phenylanthranilic acid (NPAA). RPA-1 can be detected in urine at early stages of toxicity and correlates well with the histopathology observed. We also characterized the biochemical properties of RPA-1 and found that the antigen is a high molecular weight membrane bound glycoprotein, with the epitope likely to be carried on an N-linked carbohydrate structure. This study demonstrates that RPA-1 is an excellent marker of RPN that can be used to detect this toxicity in preclinical safety testing.