The Cost-Effectiveness of Financial Incentives to Achieve Heroin Abstinence in Individuals With Heroin Use Disorder Starting New Treatment Episodes: A Cluster Randomized Trial-Based Economic Evaluation.

OBJECTIVES: Cost-effectiveness analysis of two 12-week contingency management (CM) schedules targeting heroin abstinence or attendance at weekly keyworker appointments for opioid agonist treatment compared with treatment as usual (TAU). METHODS: A cost-effectiveness analysis was conducted alongside a cluster randomized trial of 552 patients from 34 clusters (drug treatment clinics) randomly allocated 1:1:1 to opioid agonist treatment plus weekly keyworker appointments with (1) CM targeted at heroin abstinence (CM abstinence), (2) CM targeted at on-time attendance at weekly appointments (CM attendance), or (3) no CM (TAU). The primary cost-effectiveness analysis at 24 weeks after randomization took a societal cost perspective with effects measured in heroin-negative urine samples. RESULTS: At 24 weeks, mean differences in weekly heroin-negative urine results compared with TAU were 0.252 (95% confidence interval [CI] -0.397 to 0.901) for CM abstinence and 0.089 (95% CI -0.223 to 0.402) for CM attendance. Mean differences in costs were £2562 (95% CI £32-£5092) for CM abstinence and £317 (95% CI -£882 to £1518) for CM attendance. Incremental cost-effectiveness ratios were £10 167 per additional heroin-free urine for CM abstinence and £3562 for CM attendance with low probabilities of cost-effectiveness of 3.5% and 36%, respectively. Results were sensitive to timing of follow-up for CM attendance, which dominated TAU (better outcomes, lower costs) at 12 weeks, with an 88.4% probability of being cost-effective. Probability of cost-effectiveness remained low for CM abstinence (8.6%). CONCLUSIONS: Financial incentives targeted toward heroin abstinence and treatment attendance were not cost-effective over the 24-week follow-up. Nevertheless, CM attendance was cost-effective over the treatment period (12 weeks), when participants were receiving keyworker appointments and incentives.

Large tumour volume reduction of IDH-mutated anaplastic glioma involving the insular region following radiotherapy.

BACKGROUND: The impact of near-total resection of IDH-mutated anaplastic glioma (IDHmutAG) is well-established but there remains uncertainty of benefit in tumours of the insular cortex where the extent of safe resection may be limited. This study aimed to assess tumour volume reduction in patients following IMRT and impact of residual post-surgical volume. METHODS AND MATERIALS: Patients with IDHmutAG involving insular cortex managed with IMRT from 2008 to 2019 had baseline patient, tumour and treatment factors recorded. Volumetric assessment of residual disease on MRI was performed at baseline, month+ 3 and month+ 12 post-IMRT. Potential prognostic factors were analysed for tumour reduction and relapse-free survival, and assessed by log-rank and Cox regression analyses. RESULTS: Thirty two patients with IDHmutAG of the insular cortex were managed with median follow-up post-IMRT of 67.2 months. Pathology was anaplastic astrocytoma (AAmut) in 20, and anaplastic oligodendroglioma (AOD) in 12 patients. Median pre-IMRT volume on T1 and T2Flair was 24.3cm3 and 52.2cm3. Twenty-seven patients were alive with 5-year relapse-free survival of 80%. There was a median 67 and 64% reduction from baseline occurring at 3 months post-IMRT for T1 and T2Flair respectively; and subsequent median 78 and 73% at 12 months. At 12 months AOD patients had median 83% T1 volume reduction compared to 63% in AAmut (p < 0.01). There was no difference on T2Flair volume (p = 0.64). No other pathological factors influenced volume reduction at 12 months. No factors were associated with relapse-free survival including baseline T1 (p = 0.52) and T2Flair (p = 0.93) volume. CONCLUSION: IMRT provides large tumour volume reduction in IDHmutAG of the insular cortex. While maximal safe debulking remains standard of care when feasible, this patient cohort reported no significant negative impact of residual disease volume on relapse-free survival.

Tumor-Associated Fibroblast-Targeting Nanoparticles for Enhancing Solid Tumor Therapy: Progress and Challenges.

Even though nanoparticle drug delivery systems (nanoDDSs) have improved antitumor efficacy by delivering more drugs to tumor sites compared to free and unencapsulated therapeutics, achieving satisfactory distribution and penetration of nanoDDSs inside solid tumors, especially in stromal fibrous tumors, remains challenging. As one of the most common stromal cells in solid tumors, tumor-associated fibroblasts (TAFs) not only promote tumor growth and metastasis but also reduce the drug delivery efficiency of nanoparticles through the tumor's inherent physical and physiological barriers. Thus, TAFs have been emerging as attractive targets, and TAF-targeting nanotherapeutics have been extensively explored to enhance the tumor delivery efficiency and efficacy of various anticancer agents. The purpose of this Review is to opportunely summarize the underlying mechanisms of TAFs on obstructing nanoparticle-mediated drug delivery into tumors and discuss the current advances of a plethora of nanotherapeutic approaches for effectively targeting TAFs.

Lymphocytic Hypophysitis Presenting as Bilateral Abducens Nerve Palsy: A Case Report.

Lymphocytic hypophysitis (LYH) is a neuroendocrine disorder characterised by autoimmune inflammation of the pituitary gland with varying degrees of pituitary dysfunction, visual field defects and ocular motility disturbance. The authors report an interesting case of a 50-year-old woman presenting with intermittent bilateral abduction deficits. Neuroimaging and histopathological findings are presented. To the authors' knowledge, this is the first report of recurrent horizontal binocular diplopia and complete bilateral internal carotid artery occlusion in association with LYH.

Use of contingency management incentives to improve completion of hepatitis B vaccination in people undergoing treatment for heroin dependence: a cluster randomised trial.

BACKGROUND: Poor adherence to treatment diminishes its individual and public health benefit. Financial incentives, provided on the condition of treatment attendance, could address this problem. Injecting drug users are a high-risk group for hepatitis B virus (HBV) infection and transmission, but adherence to vaccination programmes is poor. We aimed to assess whether contingency management delivered in routine clinical practice increased the completion of HBV vaccination in individuals receiving opioid substitution therapy. METHODS: In our cluster randomised controlled trial, we enrolled participants at 12 National Health Service drug treatment services in the UK that provided opioid substitution therapy and nurse-led HBV vaccination with a super-accelerated schedule (vaccination days 0, 7, and 21). Clusters were randomly allocated 1:1:1 to provide vaccination without incentive (treatment as usual), with fixed value contingency management (three £10 vouchers), or escalating value contingency management (£5, £10, and £15 vouchers). Both contingency management schedules rewarded on-time attendance at appointments. The primary outcome was completion of clinically appropriate HBV vaccination within 28 days. We also did sensitivity analyses that examined vaccination completion with full adherence to appointment times and within a 3 month window. The trial is registered with Current Controlled Trials, number ISRCTN72794493. FINDINGS: Between March 16, 2011, and April 26, 2012, we enrolled 210 eligible participants. Compared with six (9%) of 67 participants treated as usual, 35 (45%) of 78 participants in the fixed value contingency management group met the primary outcome measure (odds ratio 12·1, 95% CI 3·7-39·9; p<0·0001), as did 32 (49%) of 65 participants in the escalating value contingency management group (14·0, 4·2-46·2; p<0·0001). These differences remained significant with sensitivity analyses. INTERPRETATION: Modest financial incentives delivered in routine clinical practice significantly improve adherence to, and completion of, HBV vaccination programmes in patients receiving opioid substitution therapy. Achievement of this improvement in routine clinical practice should now prompt actual implementation. Drug treatment providers should employ contingency management to promote adherence to vaccination programmes. The effectiveness of routine use of contingency management to achieve long-term behaviour change remains unknown. FUNDING: National Institute for Health Research (RP-PG-0707-10149).

Elbow hemiarthroplasty using a "triceps-on" approach for the management of acute distal humeral fractures.

BACKGROUND: Total elbow arthroplasty is an established option for the primary treatment of acute distal humeral fractures, but there are sparse data regarding elbow hemiarthroplasty (EHA) as an alternative. We present the outcome of EHA performed with a modular anatomic prosthesis and a "triceps-on" surgical technique. METHODS: Eighteen consecutive patients underwent EHA for an acute fracture. Two patients died, leaving a study group of 16 patients with minimum 2-year follow-up. Clinical evaluation included range of motion; Mayo Elbow Performance Score; Quick Disabilities of the Arm, Shoulder, and Hand score; and Oxford Elbow Score. Radiographic assessment looked at alignment, evidence of loosening, ulnar and radial head wear, heterotopic ossification, and whether healing of the condyles had occurred. RESULTS: Mean follow-up was 35 months (24-79 months). The mean scores were as follows: Mayo Elbow Performance Score, 89.6; shortened Disabilities of the Arm, Shoulder, and Hand score, 11.2; and Oxford Elbow Score, 43.7. The mean flexion and pronation-supination arcs were 116° and 172° respectively. Radial head wear was absent in 13 patients and mild in 3. Ulnar wear was absent in 6 patients, mild in 8, and moderate in 2. Wear was not associated with greater pain or inferior functional scores. There was no sign of aseptic loosening, and complete condylar bone union occurred in 15 elbows. There was 1 complication, a transient ulnar nerve neurapraxia that resolved without intervention. CONCLUSION: EHA with a modular anatomic implant using a triceps-on approach is a reliable technique for the management of acute unreconstructible distal humeral fractures in older patients.

MGMT expression and pituitary tumours: relationship to tumour biology.

Over the past half decade, temozolomide, an oral akylating chemotherapeutic agent, has been shown to have significant activity in the management of aggressive pituitary tumours. The expression of 06-methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme, is an important predictor of response to therapy. Low MGMT expression has been reported with a higher frequency amongst more aggressive pituitary tumours, suggesting MGMT may play a role in pituitary tumour progression. In this study, we performed a microarray analysis to determine whether there was a distinct gene expression profile between tumours with low MGMT and high MGMT expression. Overall, 1,403 differentially expressed genes were identified with raw p values less than 0.05. Gene set enrichment analysis (GSEA) revealed significant differences in the gene expression profile between high and low MGMT expressing pituitary tumours. High MGMT expressing pituitary tumours were found to have upregulation of components of the FGFR family and downstream signaling cascades such as PI3 K/Akt and MAPK pathways. Activation of genes involved in the DNA damage response and DNA repair pathways, as well as genes involved in transcription, were identified in pituitary tumours with low MGMT expression. These results form the basis of our proposed model to describe the role of MGMT in pituitary tumorigenesis.

Immunogenic camptothesome nanovesicles comprising sphingomyelin-derived camptothecin bilayers for safe and synergistic cancer immunochemotherapy.

Despite the enormous therapeutic potential of immune checkpoint blockade (ICB), it benefits only a small subset of patients. Some chemotherapeutics can switch 'immune-cold' tumours to 'immune-hot' to synergize with ICB. However, safe and universal therapeutic platforms implementing such immune effects remain scarce. We demonstrate that sphingomyelin-derived camptothecin nanovesicles (camptothesomes) elicit potent granzyme-B- and perforin-mediated cytotoxic T lymphocyte (CTL) responses, potentiating PD-L1/PD-1 co-blockade to eradicate subcutaneous MC38 adenocarcinoma with developed memory immunity. In addition, camptothesomes improve the pharmacokinetics and lactone stability of camptothecin, avoid systemic toxicities, penetrate deeply into the tumour and outperform the antitumour efficacy of Onivyde. Camptothesome co-load the indoleamine 2,3-dioxygenase inhibitor indoximod into its interior using the lipid-bilayer-crossing capability of the immunogenic cell death inducer doxorubicin, eliminating clinically relevant advanced orthotopic CT26-Luc tumours and late-stage B16-F10-Luc2 melanoma, and achieving complete metastasis remission when combined with ICB and folate targeting. The sphingomyelin-derived nanotherapeutic platform and doxorubicin-enabled transmembrane transporting technology are generalizable to various therapeutics, paving the way for transformation of the cancer immunochemotherapy paradigm.

Using a pragmatically adapted, low-cost contingency management intervention to promote heroin abstinence in individuals undergoing treatment for heroin use disorder in UK drug services (PRAISE): a cluster randomised trial.

INTRODUCTION: Most individuals treated for heroin use disorder receive opioid agonist treatment (OAT)(methadone or buprenorphine). However, OAT is associated with high attrition and persistent, occasional heroin use. There is some evidence for the effectiveness of contingency management (CM), a behavioural intervention involving modest financial incentives, in encouraging drug abstinence when applied adjunctively with OAT. UK drug services have a minimal track record of applying CM and limited resources to implement it. We assessed a CM intervention pragmatically adapted for ease of implementation in UK drug services to promote heroin abstinence among individuals receiving OAT. DESIGN: Cluster randomised controlled trial. SETTING AND PARTICIPANTS: 552 adults with heroin use disorder (target 660) enrolled from 34 clusters (drug treatment clinics) in England between November 2012 and October 2015. INTERVENTIONS: Clusters were randomly allocated 1:1:1 to OAT plus 12× weekly appointments with: (1) CM targeted at opiate abstinence at appointments (CM Abstinence); (2) CM targeted at on-time attendance at appointments (CM Attendance); or (3) no CM (treatment as usual; TAU). Modifications included monitoring behaviour weekly and fixed incentives schedule. MEASUREMENTS: Primary outcome: heroin abstinence measured by heroin-free urines (weeks 9-12). SECONDARY OUTCOMES: heroin abstinence 12 weeks after discontinuation of CM (weeks 21-24); attendance; self-reported drug use, physical and mental health. RESULTS: CM Attendance was superior to TAU in encouraging heroin abstinence. Odds of a heroin-negative urine in weeks 9-12 was statistically significantly greater in CM Attendance compared with TAU (OR=2.1; 95% CI 1.1 to 3.9; p=0.030). CM Abstinence was not superior to TAU (OR=1.6; 95% CI 0.9 to 3.0; p=0.146) or CM Attendance (OR=1.3; 95% CI 0.7 to 2.4; p=0.438) (not statistically significant differences). Reductions in heroin use were not sustained at 21-24 weeks. No differences between groups in self-reported heroin use. CONCLUSIONS: A pragmatically adapted CM intervention for routine use in UK drug services was moderately effective in encouraging heroin abstinence compared with no CM only when targeted at attendance. CM targeted at abstinence was not effective. TRIAL REGISTRATION NUMBER: ISRCTN 01591254.

Self-assembling prodrug nanotherapeutics for synergistic tumor targeted drug delivery.

Self-assembling prodrugs represents a robust and effective nanotherapeutic approach for delivering poorly soluble anticancer drugs. With numerous intrinsic advantages, self-assembling prodrugs possess the maximum drug loading capacity, controlled drug release kinetics, prolonged blood circulation, and preferential tumor accumulation based on the enhanced permeability and retention (EPR) effect. These prodrug conjugates allow for efficient self-assembly into nanodrugs with the potential of encapsulating other therapeutic agents that have different molecular targets, enabling simultaneous temporal-spatial release of drugs for synergistic antitumor efficacy with reduced systemic side effects. The aim of this review is to summarize the recent progress of self-assembling prodrug cancer nanotherapeutics that are made through conjugating therapeutically active agents to Polyethylene glycol, Vitamin E, or drugs with different physicochemical properties via rational design, for synergistic tumor targeted drug delivery. STATEMENT OF SIGNIFICANCE: All current FDA-approved nanomedicines use inert biomaterials as drug delivery carriers. These biomaterials lack any therapeutic potential, contributing not only to the cost, but may also elicit severe unfavorable adverse effects. Despite the reduction in toxicity associated with the payload, these nanotherapeutics have been met with limited clinical success, likely due to the monotherapy regimen. The self-assembling prodrug (SAP) has been emerging as a powerful platform for enhancing efficacy through co-delivering other therapeutic modalities with distinct molecular targets. Herein, we opportunely present a comprehensive review article summarizing three unique approaches of making SAP for synergistic drug delivery: pegylation, vitamin E-derivatization, and drug-drug conjugation. These SAPs may inevitably pave the way for developing more efficacious, clinically translatable, combination cancer nanotherapies.

Arthroscopic stabilisation for shoulder instability.

Since its first description over 30 years ago arthroscopic stabilisation has evolved. With improvements in knowledge, surgical techniques and materials technology, arthroscopic bankart repair has become the most widely used method for treating patients with symptomatic anterior shoulder instability. These procedures are typically performed in a younger, high demand patient population after a primary dislocation or to treat recurrent instability. A thorough clinical evaluation is required in the clinic setting not only to fully understand the injury pattern but also consider patient expectations prior to embarking on surgery. Diagnostic imaging will aid the clinician in determining the soft tissue pathology as well as assessing bone loss, which facilitates surgical decision-making. Selected patients may benefit from adjunctive procedures such as a remplissage for an "engaging" Hill-sachs lesion. This review will focus on the indications, pre-operative considerations, surgical techniques and outcomes of arthroscopic stabilisation.

Low O6-methylguanine-DNA methyltransferase (MGMT) expression and response to temozolomide in aggressive pituitary tumours.

CONTEXT: Recent case reports detail the successful use of temozolomide in the management of aggressive pituitary tumours. O(6)-methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein that counteracts the effect of temozolomide. OBJECTIVE: To study MGMT expression in pituitary tumours and consider whether MGMT expression is associated with response to temozolomide therapy in aggressive pituitary tumours. PATIENTS: We report two patients with aggressive pituitary tumours treated with temozolomide, one who responded to temozolomide and the other who did not. MGMT expression was assessed in a further 88 archived pituitary tumour samples. DESIGN: MGMT expression was assessed by immunohistochemistry. MGMT promoter methylation was studied by methylation-specific polymerase chain reaction (MSP), sequencing of MGMT was performed and loss of heterozygosity (LOH) analysis undertaken. RESULTS: Low MGMT expression and MGMT promoter methylation were found in the pituitary tumour of the patient who responded to temozolomide. Conversely, high MGMT expression was seen in the patient demonstrating a poor response to temozolomide. Eleven out of 88 archived tumour samples (13%) had low MGMT expression. Prolactinomas were more likely to have low MGMT expression compared with other pituitary tumour subtypes (P < 0.001). There was no significant difference in MGMT expression between invasive and noninvasive tumours, or between recurrent and nonrecurrent tumours. A significant inverse correlation was found between MGMT expression and promoter methylation (P = 0.012). CONCLUSION: MGMT expression as assessed by immunohistochemistry may predict response to temozolomide therapy in patients with aggressive pituitary tumours. MGMT promoter methylation is likely to explain low MGMT expression in some, but not all, pituitary tumours.

Loss of prostaglandin D2 synthase: a key molecular event in the transition of a low-grade astrocytoma to an anaplastic astrocytoma.

Reduction in the mRNA and protein expression of lipocalin-like prostaglandin D(2) (PGD(2)) synthase (PGDS), the main arachidonic acid metabolite produced in neurons and glial cells of the central nervous system, is a significant biological event involved in the malignant progression of astrocytomas and is predictive of poor survival. In vitro, the addition of the main PGDS metabolite, PGD(2), to A172 glioblastoma cells devoid of PGDS resulted in antiproliferative activity and cell death. In vitro PGD(2) substitution also enhanced the efficacy of cyclo-oxygenase-2 inhibitors. This finding has exciting implications for early interventional efforts for the grade 2 and 3 astrocytomas.

Focal radiation therapy for limited brain metastases is associated with high rates of local control and low subsequent whole brain radiation therapy.

BACKGROUND: Assess clinical outcomes of focal radiotherapy (RT) in patients with limited brain metastasis (LBM) with whole brain RT (WBRT) avoidance. METHODS: Patients diagnosed with LBM were entered into a database between January 2010 and February 2017. Patients were recommended WBRT avoidance with focal therapy and three-monthly magnetic resonance imaging. The primary endpoint was overall survival. Secondary endpoints included progression-free survival, initial-site failure (ISF), distant brain relapse (DBF), leptomeningeal disease and rate of WBRT. Analysis involved Kaplan-Meier survival estimate with log-rank tests and Cox-regression analysis. RESULTS: One hundred and sixty-six patients were managed with median follow-up of 13 months and median overall survival of 15 months (95% confidence interval (CI) 10.8-19.2). Eighty-three patients had central nervous system (CNS) relapse with median progression-free survival of 11 months (95% CI 6.7-15.3), of which most failures were DBF (83.1%) with 27 ISF (32.5%). Of the ISFs, 12 (43%) had surgery alone, six had chemotherapy alone and nine received RT. Surgery or chemotherapy alone compared with RT had a significantly higher incidence of ISF with a hazard ratio of 4.96 (P < 0.0001, 95% CI 2.10-11.83) and 6.54 (P = 0.001, 95% CI 2.26-18.87), respectively. WBRT was utilized in only 24 patients, with 83% patients free of WBRT at 12 months. On univariate analysis, number of metastases (P = 0.04), symptomatic extracranial disease (P = 0.04) and early CNS relapse within 6 months (P < 0.01) had worse survival. No grade 3-4 toxicity events were noted in 129 patients undergoing RT. CONCLUSION: Focal RT has a low rate of ISF with low toxicity in patients with LBMs. CNS progression was mainly DBF with low rates of salvage WBRT.

Wnt pathway inhibitors are strongly down-regulated in pituitary tumors.

The etiology of sporadic pituitary tumors is currently unknown. The Wnt pathways have been implicated in the pathogenesis of a variety of human tumors, but the role of these pathways in pituitary tumors is unclear. Microarray analysis using the Affymetrix HG U133 plus 2.0 GeneChips identified four secreted frizzled-related protein (sFRP) family members of Wnt pathway inhibitors that were differentially expressed in both nonfunctioning and clinically functioning pituitary tumors (n = 20) compared with normal pituitary controls (n = 3). Reduced tumor expression of Wnt inhibitory factor-1 (WIF1), sFRP2, and sFRP4 mRNA was confirmed by real-time quantitative RT-PCR (P <0.001 and P = 0.002 and 0.013, respectively) in all pituitary subtypes. Hypermethylation of the WIF1 promoter was present in 88% of the pituitary tumors (n = 41). Seventy-six percent of pituitary tumors demonstrated absent or weak cytoplasmic WIF1 staining by immunohistochemistry (n = 41), although preserved staining was seen in some functioning tumors, with strong staining in 92% of normal pituitary controls (n = 13). The Wnt pathway target gene cyclin D1 was found to be up-regulated specifically in the nonfunctioning pituitary tumors compared with controls at both mRNA and protein level, supportive of activation of the Wnt-beta-catenin pathway. Nuclear accumulation of beta-catenin, however, was not observed in any pituitary tumors (n = 70). By transfecting GH3 cells with WIF1, decreased cell proliferation and colony formation was observed compared with empty vector controls. In conclusion, our data suggest that WIF1 may be a tumor suppressor, specifically in nonfunctioning pituitary tumors, and that the Wnt pathways are important in pituitary tumorigenesis.

Chiari malformation, cervical disc prolapse and syringomyelia--always think twice.

We present the case of a 36-year-old man with neck pain and parasthesia of both upper limbs. Magnetic resonance imaging demonstrated a cervical disc protrusion with spinal cord compression, a Chiari I malformation and cervical syringomyelia. On clinical grounds it was suspected that the cervical stenosis was the symptomatic pathology and an anterior cervical decompression was performed, followed by arthroplasty. Post-operative imaging demonstrated adequate canal decompression, preserved cervical mobility and near-complete resolution of the syrinx. Syringomyelia has a multitude of causes and synchronous pathology can occur. Cervical spondylosis is infrequently associated with syringomyelia. Chiari I malformations are increasingly incidentally detected and asymptomatic. This first report of arthroplasty for cervical spondylosis associated with syringomyelia adds to the growing body of experience with this new technology.

IQGAP1 and IGFBP2: valuable biomarkers for determining prognosis in glioma patients.

Clinical treatment decisions and the survival outcomes of patients with gliomas are directly impacted by accurate tumor classification. New and more reliable prognostic markers are needed to better identify the variable duration of survival among histologically defined glioma grades. Microarray expression analysis and immunohistochemistry were used to identify biomarkers associated with gliomas with more aggressive biologic behaviors. The protein expression of IQGAP1 and IGFBP2, when used in conjunction with the World Health Organization grading system, readily identified and defined a subgroup of patients with grade III gliomas whose prognosis was poor. In addition, in patients with glioblastoma multiforme, in whom IQGAP1 and IGFBP2 were absent, long-term survival of more than 3 years was observed. The use of these markers confirmed a nonuniform distribution of survival in those with World Health Organization grade III and IV tumors. Thus, IQGAP1 and IGFBP2 immunostaining supplements current histologic grading by offering additional prognostic and predictive information.

Idiopathic intradural dorsal thoracic arachnoid cysts: A case series and review of the literature.

BACKGROUND: Spinal intradural arachnoid cysts (SIAC) are cerebrospinal fluid (CSF) filled sacs formed by arachnoid membranes and may be either idiopathic or acquired. Idiopathic cysts represent a separate entity and their aetiology remains uncertain. By far the most difficult differential diagnosis is distinguishing between idiopathic anterior spinal cord herniation (IASCH) and dorsal thoracic intradural arachnoid cysts (TIAC), due to their similarity in radiological appearance. Cine-mode (SSFP) is emerging as a novel technique in the diagnosis and operative planning of SIAC. METHOD: Retrospective analysis of patients with idiopathic TIACs that were surgically managed at Royal North Shore Hospital and North Shore Private Hospital between November 2000 and November 2015. RESULTS: Ten patients were included in this study. Age ranged from 20 to 77years with a mean age of 60years and a female preponderance. The most common clinical features were progressive gait ataxia and lower limb myelopathy. Radicular pain tends to improve following surgery, however gait ataxia may not. DISCUSSION: While there are circumstances in which the distinction between dorsal thoracic intradural arachnoid cysts and idiopathic anterior spinal cord herniation are radiologically obvious, in cases where the appearances are less clear, cine-mode SSFP MRI imaging can provide an invaluable tool to differentiate these pathologies and lead the clinician towards the correct diagnosis and management. The mainstay of surgical management for dorsal TIACs is laminectomy and cyst excision or fenestration. Surgery for gait ataxia should be aimed towards preventing deterioration, while maintaining the potential for symptomatic improvement, whereas surgery for radicular pain should be curative.

Survival of glioblastoma patients related to presenting symptoms, brain site and treatment variables.

This retrospective study of 133 patients with glioblastoma multiforme evaluates survival times post-radiation in patients stratified in respect to age, presenting symptoms, tumour location, extent of surgery, and radiation dose delivered. Presenting features were coded as seizure, loss of consciousness, headache, speech or visual disturbance, weakness and confusion, as were tumour sites within the brain. Other parameters assessed included side of brain, age, extent of surgery and radiation dose. Statistical evaluation was undertaken by univariate and multivariate analyses to identify factors leading to enhanced survival. The median survival post-radiation was 10 months. A trend to improved early survival was demonstrated in patients presenting with acute and debilitating symptoms. The data presented reveals improved outcomes for patients younger than 60 years, particularly if radical surgery is undertaken with higher dose radiation. It is postulated that patients presenting with acute signs and symptoms are investigated earlier and are referred more promptly for treatment.

Intramedullary fixation of pertrochanteric fractures after hip resurfacing arthroplasty - Do we have the answer? Case report and literature review.

OBJECTIVE: To report a case of a peri-prosthetic hip fracture fixed using a previously unreported technique of intramedullary nailing with dual proximal fixation. CASE SUMMARY: An 81-year-old nursing home resident suffered a multi-fragmentary peri-prosthetic hip fracture around a Birmingham Hip Resurfacing arthroplasty (BHR), which was fixed using a novel technique. DISCUSSION: Such fractures pose a significant surgical dilemma with regards to the optimal method of treatment. The increasing popularity of these implants suggests that these fractures will become increasingly common. CONCLUSION: We believe that our technique provides a practical and satisfactory solution to these fractures.