Lithium isotopes differentially modify mitochondrial amorphous calcium phosphate cluster size distribution and calcium capacity.

Lithium is commonly prescribed as a mood stabilizer in a variety of mental health conditions, yet its molecular mode of action is incompletely understood. Many cellular events associated with lithium appear tied to mitochondrial function. Further, recent evidence suggests that lithium bioactivities are isotope specific. Here we focus on lithium effects related to mitochondrial calcium handling. Lithium protected against calcium-induced permeability transition and decreased the calcium capacity of liver mitochondria at a clinically relevant concentration. In contrast, brain mitochondrial calcium capacity was increased by lithium. Surprisingly, 7Li acted more potently than 6Li on calcium capacity, yet 6Li was more effective at delaying permeability transition. The size distribution of amorphous calcium phosphate colloids formed in vitro was differentially affected by lithium isotopes, providing a mechanistic basis for the observed isotope specific effects on mitochondrial calcium handling. This work highlights a need to better understand how mitochondrial calcium stores are structurally regulated and provides key considerations for future formulations of lithium-based therapeutics.

Para-spinal abscess presenting with abdominal pain-a case report of 'red herring' symptoms.

INTRODUCTION: Paraspinal abscesses are rare infections affecting the paraspinal muscles and soft tissues. An evolving abscess may pose a threat to the spinal cord via the compressive effect which can manifest as impaired motor or sensory function at the corresponding vertebral level. Paraspinal abscess is often a late diagnosis due to non-specific symptoms at presentation. This results in high morbidity and mortality. CASE PRESENTATION: We describe the case of a 59-year-old female with a paraspinal abscess presenting with epigastric pain who was initially worked up for a suspected intra-abdominal pathology, however computerised tomography of the chest, abdomen, and pelvis (CTCAP) revealed no abnormality. Later, rising inflammatory markers, accompanied by worsening cervicalgia, prompted a CT of the head, neck and thorax which revealed a soft tissue abscess compressing the thecal sac at cervical levels 1 to 3 (C1-3). This was successfully managed with radiologically guided drainage and long-term intravenous antibiotics. Our patient made a full recovery and a repeat MRI demonstrated resolution of the abscess. CONCLUSION: We demonstrate that spinal abscess can present with a misleading combination of symptoms and highlight the importance of considering rarer differentials in the face of an evolving clinical picture. Our case also demonstrates that once the correct diagnosis is reached, patients can make an excellent recovery from uncomplicated spinal abscesses.

Search for lithium isotope effects in neuronal HT22 cells.

Lithium has been used as a treatment for bipolar disorder for over half a century, but there has thus far been no clinical differentiation made between the two naturally occurring stable isotopes (6Li and 7Li). While the natural lithium salts commonly used in treatments are composed of a mixture of these two stable isotopes (approximately 7.59% 6Li and 92.41% 7Li), some preliminary research indicates the above two stable isotopes of lithium may have differential effects on rat behaviour and neurophysiology. Here, we evaluate whether lithium isotopes may have distinct effects on HT22 neuronal cell viability, GSK-3-ß phosphorylation in HT22 cells, and GSK-3-ß kinase activity. We report no significant difference in lithium isotope toxicity on HT22 cells, nor in GSK-3-ß phosphorylation, nor in GSK-3-ß kinase activity between the two isotopes of lithium.

Spondylodiscitis-a cohort analysis of its identification and management.

PURPOSE: Discitis represents infection of the intervertebral disc and osteomyelitis of the adjacent end plates. Classically, patients present with fever and back pain. Varied presentations and lack of adherence to guidelines lead to great variation in its identification and management. The primary objective of this study was to conduct a cohort analysis, assessing the identification and management of discitis, in a busy secondary orthopaedic centre. METHODS: A retrospective study was conducted, of cases diagnosed and treated for discitis, in a secondary orthopaedic department, within the UK from January 2017 to October 2019. During this time period, all patients who underwent magnetic resonance imaging (MRI) spine were identified. Patients with MRI-proven discitis were then added into the study. RESULTS: A total of 152 MRIs showed radiographic features of discitis. Of these, only 38 had a clear clinical correlation. Back pain was the most common presenting complaint followed by fever. The commonest site of involvement was vertebral levels L5 and S1. All patients had baseline bloods, and most, but not all, had blood cultures taken. Staphylococcus aureus was the most frequently isolated, causative organism. The mainstay of treatment was intravenous flucloxacillin, with most patients requiring a minimum of six weeks. CONCLUSION: Our study has helped define the population of patients presenting with discitis, in a busy secondary orthopedic center. Analyzing over two years of data has provided us with valuable insight into the most appropriate diagnostics and management for discitis.

Comparing predicted and observed morbidity and mortality between emergency laparotomies conducted during the day and overnight at a district general hospital.

BACKGROUND: It is generally expected that emergency laparotomies performed at night confer a higher risk and thus outcomes are worse. This study hopes to determine whether there is a difference in risk of cases presenting at night, and overall outcome. METHODS: Data were retrospectively obtained using local notes archival software to obtain predicted and observed mortality, ASA (American Society of Anesthesiologists) grade and length of stay of emergency laparotomies conducted between August 2019 and March 2020. Day cases were defined as knife to skin time (KTS) between 08:00 and 19:59, whilst night cases were defined as KTS between 20:00 and 07:59. RESULTS: In all, 81 emergency laparotomies were performed during day-time hours over the 8­month period; 32 were performed overnight. Median ASA grade was 3 for both. Median length of stay was similar: 11 day, 12 overnight. Median P-POSSUM (Portsmouth Physiological and Operative Severity Score for enUmeration of Mortality and Morbidity) morbidity score of day cases was 52% compared to 53.2% at night. Median mortality score of day cases was 5.6%, whilst at night was 2.7% (p = 0.27). Observed mortality after day cases was 13.5%, and overnight was 9.3%. Observed morbidity was 46.9% after day cases and 50% overnight. CONCLUSION: There was no statistically significant difference between predicted or observed morbidity and mortality between emergency laparotomies conducted during the day and those conducted overnight.

A Case of Bilateral Baxter's Neuropathy Secondary to Plantar Fasciitis.

Heel pain is 1 of the most common presentations to the foot surgeon, and its causes are multifactorial. Baxter's neuropathy is caused by an impingement of the inferior calcaneal nerve and has been reported to be responsible for up to 20% of heel pain. The diagnostic imaging features are striking, with inflammation or atrophy of the abductor digiti minimi muscle. Multiple studies have found that the prevalence of this finding is much greater than initially thought. However, it is more unusual to find bilateral and symmetrical features. The possible causes of this condition lie along the course of the inferior calcaneal nerve. Management is focused on treating the underlying condition, with conservative therapy and steroid injection as the mainstay. Refractory cases may require surgical release. We present the case of a 56-year-old female presenting with bilateral foot pain. Imaging reveals symmetrical abductor digiti minimi atrophy associated with bilateral plantar fasciitis. These appearances are well demonstrated on both magnetic resonance imaging and ultrasound.

Interobserver and intraobserver reliability assessment of calcaneal fracture classification systems.

The aim of the present study was to assess the reliability of commonly used intra-articular calcaneal fracture classification systems and to compare them with the newer AO Integral Classification of Injuries (ICI) system. Forty computed tomography and radiographic images of 40 intra-articular calcaneal fractures were reviewed independently by 3 reviewers on 2 separate occasions and classified according to the Essex-Lopresti, Atkins, Zwipp and Tscherne, Sanders, and AO-ICI classification systems. The reviewers were unaware of the patients' identity and all aspects of clinical care. The data were analyzed using kappa (κ) statistics to assess the intra- and interobserver reliability. The κ values were calculated for Essex-Lopresti (κ = 0.85 intraobserver, κ = 0.78 interobserver), Atkins (κ = 0.42 intraobserver, κ = 0.73 interobserver), Zwipp and Tscherne (κ = 0.40 intraobserver, κ = 0.47 interobserver), Sanders (κ = 0.31 intraobserver, κ = 0.35 interobserver), and AO-ICI (κ = 0.41 intraobserver, κ = 0.33 interobserver). The AO-ICI classification system had levels of reproducibility similar to that of the Sanders classification, currently the most widely used system. The Essex-Lopresti classification demonstrated improved reliability compared with that reported in previous studies. This can be attributed to using sagittal computed tomography images, in addition to the originally described plain radiographs, for assessment. This improvement is relevant because of its accepted prognostic predictability.

Informed consent in trauma: does written information improve patient recall of risks? A prospective randomised study.

Informed consent is vital to good surgical practice. Pain, sedative medication and psychological distress resulting from trauma are likely to adversely affect a patient's ability to understand and retain information thus impairing the quality of the consent process. This study aims to assess whether provision of written information improves trauma patient's recall of the risks associated with their surgery. 121 consecutive trauma patients were randomised to receive structured verbal information or structured verbal information with the addition of supplementary written information at the time of obtaining consent for their surgery. Patients were followed up post-operatively (mean 3.2 days) with a questionnaire to assess recall of risks discussed during the consent interview and satisfaction with the consent process. Recall of risks discussed in the consent interview was found to be significantly improved in the group receiving written and verbal information compared to verbal information alone (mean questionnaire score 41% vs. 64%), p=0.0014 using the Mann-Whitney U test. Patient satisfaction with the consent process was improved in the group receiving written and verbal information and 90% of patients in both groups expressed a preference for both written and verbal information compared to verbal information alone. Patients awaiting surgery following trauma can pose a challenge to adequately inform about benefits conferred, the likely post operative course and potential risks. Written information is a simple and cost-effective means to improve the consent process and was popular with patients.

Tibiotalocalcaneal arthrodesis with a curved, interlocking, intramedullary nail.

BACKGROUND: Tibiotalocalcaneal fusion with a straight rod has a risk of damaging the lateral plantar neurovascular structures and may interfere with maintaining normal heel valgus position.We report the results of a prospective study of tibiotalocalcaneal (TTC) arthrodesis with a short, anatomically curved interlocking, intramedullary nail. MATERIAL AND METHODS: Forty-five arthrodesis in 42 patients, performed between Jan 2003 and Oct 2008, were prospectively followed. The mean followup was 48 (range, 10 to 74) months. The main indications for the procedure were failed ankle arthrodesis with progressive subtalar arthritis, failed ankle arthroplasty and complex hindfoot deformity. The outcome was measured by a combination of pre and postoperative clinical examination, AOFAS hindfoot scores, SF-12 scores and radiological assessment. RESULTS: Union rate was 89% (40/45). Eighty-two percent (37/45) reported improvement in pain and 73% (33/45) had improved foot function. Satisfactory hindfoot alignment was achieved in 84% (38/45). Postoperatively there was a mean improvement in the AOFAS score of 37. Complications included a below knee amputation for persistent deep infection, five nonunions, and three delayed unions. Four nails, six proximal and six distal locking screws were removed for various causes. Other complications included two perioperative fractures, four superficial wound infections and one case of lateral plantar nerve irritation. CONCLUSION: With a short, anatomically curved intramedullary nail, we had a high rate of tibiotalocalcaneal fusion with minimal plantar neurovascular complications. We believe a short, curved intramedullary nail, with its more lateral entry point, helped maintain hindfoot alignment.

Posttraumatic proximal tibial growth arrest: a rare injury managed successfully with ring fixators.

A ring fixator was used in the treatment of five patients (ages 11 to 16 years) with proximal tibial growth arrest after trauma. The mean corrections were 14.2 degrees (maximum 28 degrees , minimum 0 degrees ) in the saggital plane and 14 degrees (maximum 38 degrees , minimum 2 degrees ) in the coronal plane. Leg length discrepancy was also corrected (max 1 cm). The average time in frame was 17.8 weeks, with an average correction time of 29.8 days. Knee Society Clinical Rating System scores post operatively ranged from 95-100. All patients returned to full activity, and would accept the same treatment if offered again. The circular fixator is an effective, minimally invasive method for treating the complex deformities arising from this rare injury. Patients remain active during treatment, encouraging a rapid return to school/work activities.

The bicipital aponeurosis may be involved in the anatomical etiology of arterial compromise after swelling in supracondylar fracture.

A 7-year-old girl presented with a Gartland grade III supracondylar fracture and no radial pulse. After open reduction, it was established that the brachial artery was free of the fracture site; the limb however remained nonviable. The brachial artery was then approached anteriorly and the bicipital aponeurosis was seen to kink the artery. Once the bicipital aponeurosis was released and the remaining spasm treated with arteriotomy and papaverine, a good pulse returned. Despite the fracture being reduced and the artery remaining free of it, there remained a structural impediment to flow in the brachial artery. If the pulse does not return after fixation of a supracondylar fracture, then exploration of the brachial artery is indicated. When a patient is taken to the operating room for fixation of a supracondylar fracture, the facilities and expertise to explore the brachial artery must be made available. In centers where an on-call vascular service is not available, we recommend that the orthopaedic training programs give consideration to including "exploration of the brachial artery" as a facet of orthopaedic surgical training.

Complex regional pain syndrome (type 1): a comparison of 2 diagnostic criteria methods.

BACKGROUND: Complex regional pain syndrome (CRPS) is a common problem presenting to orthopedic surgeons or pain therapists, most frequently encountered after trauma or surgery to a limb. Because of a lack of a simple objective diagnostic test, diagnosis is reliant on clinical assessment. Prospective studies have repeatedly demonstrated a higher incidence than retrospective studies, an observation that has been challenged owing to the lack of uniformity of diagnostic criteria across specialties and workers researching the condition. METHODS: A series of 262 adult patients presenting to the Bristol Royal Infirmary with a closed unilateral distal radial fracture were assessed at a mean of 9.47 weeks after their injury by a single clinician (J.A.L.). Each assessment made allowed comparison of the modified International Association for the Study of Pain (Bruehl) criteria for the presence of CRPS with the criteria described by Atkins. FINDINGS: The incidence of CRPS was similar using either criteria (Bruehl 20.61% vs. Atkins 22.52%). Using the Bruehl criteria as a gold standard, there was strong diagnostic agreement (kappa=0.79, sensitivity=0.87, specificity=0.94). Disagreements between the 2 criteria methods were found in 19 patients. The majority of these discordances were due to differences in pain and sensory abnormality assessment. INTERPRETATION: These findings show that the Bruehl and Atkins criteria are basically concordant. The differences reflect only minor variations in the assessment of pain. Agreement between researchers in the orthopedic and pain therapy communities will allow improved understanding of CRPS.

Taylor Spatial Frame application with the aid of a fine wire half frame.

The Taylor Spatial Frame has become an important part of the trauma and reconstruction surgeon's armamentarium. We describe a technique to assist in the application of this device that does not hinder the use of the image intensifier or rely on an assistant to hold a constant position and aids provisional fracture reduction.

Computer hexapod assisted orthopaedic surgery (CHAOS) in the correction of long bone fracture and deformity.

SUMMARY: We describe a surgical technique using the Taylor Spatial Frame intraoperatively to correct complex multiplanar deformities of the distal femur prior to definitive internal fixation using minimally invasive stabilization techniques. Eight procedures were done in 7 patients. All deformities were complex oblique plane deformities, often with a rotational component, and ranged from 10 degrees valgus to 35 degrees varus; up to 45 degrees of external rotation; 10 mm of translation and in 1 case, 100 mm of shortening. All patients underwent acute intraoperative deformity correction mediated by the Taylor Spatial Frame prior to definitive internal fixation using either a percutaneous locking plate or locked intramedullary nail. Deformity correction and restoration of the mechanical axis were achieved in all cases. There were no cases of wound breakdown, infection, nerve palsy or compartment syndrome. We believe the Taylor Spatial Frame can be effectively and safely used to assist the acute correction and subsequent internal fixation of limb deformity.