Discordant dry eye disease and chronic pain: A systematic review and meta-analysis.

PURPOSE: To evaluate the relative contributions of objective and subjective indicators of dry eye disease (DED) in individuals with chronic pain conditions compared with controls. METHODS: A systematic review and meta-analysis was conducted of studies that reported the signs and symptoms of DED and/or their prevalence in individuals with chronic pain compared with controls. International Association for the Study of Pain (IASP) International Classification of Diseases (ICD)-11 codes for chronic pain conditions were applied, and outcomes defined as DED signs and symptoms. A search strategy utilised the EMBASE, Web of Science, Cochrane Library and MEDLINE databases. Risk of bias assessment was performed with the Newcastle-Ottawa scale. Random effects meta-analysis calculated mean differences (MD) and odds ratios (OR), while subgroup analysis of different chronic pain conditions explored their relative association with the signs and symptoms of DED. Evidence certainty was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE). RESULTS: Fourteen observational studies comprising 3,281,882 individuals were included. Meta-analysis found high quality evidence that individuals with chronic pain were more likely to experience symptoms of DED than controls (OR = 3.51 [95 %CI: 3.45,3.57]). These symptoms were more severe (MD = 18.53 [95 %CI: 11.90, 25.15]) than controls with a clinically meaningful effect size. Individuals with chronic pain had more rapid tear film disruption (MD = -2.45 [95 %CI: -4.20, -0.70]) and reduced tear production (MD = -5.57 [95 %CI: -9.56, -1.57]) compared with controls (with moderate evidence quality). High quality evidence revealed individuals with chronic pain had lower basal tear production (anaesthetised) than controls (MD = -2.59 [95 %CI: -3.60, -1.58]). Tear film osmolarity showed no significant differences between the chronic pain and pain-free groups. Group differences for DED signs were not considered clinically meaningful. CONCLUSION: More severe, clinically meaningful symptoms of DED were reported in individuals with chronic pain than controls, however group differences for the signs of DED were typically of limited or questionable clinical relevance. This ocular phenotype where DED is felt more than it is seen in chronic pain may reflect underlying sensory hypersensitivity, shared by both conditions and contributing to their frequent comorbidity. Advancing understanding of this potential pathophysiological mechanism may guide clinical management.

Letter to the Editor on: "The Effects of Physical Exercise on Tumor Vasculature: Systematic Review and Meta-Analysis."

Dear Editor,We read with interest the recent article "The Effects of Physical Exercise on Tumor Vasculature: Systematic Review and Meta-analysis" 1 and after careful appraisal and consideration we feel that some aspects of the data and analysis warrant further review. The study reported some promising results, namely that both chronic and acute exercise appear to improve intratumoral vascularisation in animal models. This is an important finding given increased vascularisation through tumor modulation may have the potential to improve chemotherapy delivery and efficacy 2. However, after conducting further investigations, we query several details in the data extraction and analysis decision-making that we believe impact the conclusions of this article.

Oxford knee score 1 year after TKR for osteoarthritis with reference to a normative population: What can patients expect?

Objectives: Total knee replacement (TKR) procedure is commonly carried out in patients with advanced osteoarthritis to reduce pain and increase mobility, with on average 84% rated satisfactory outcome, but some (some suggest 44%) continue to experience debilitating pain. The study aimed to investigate factors affecting pain and function outcomes (using Oxford Knee Score, OKS) one year after TKR, with normative comparison to a reference population. Design: We recruited TKR patients from one hospital (Nottinghamshire, UK); collected pre- and post-operative OKS; graded radiographs for severity of osteoarthritis (K-L grade) in a sub-group. We also collected OKS by postal survey from the local area, calculated age and sex specific normative scores and z-scores of post-operative OKS (Z-OKS). The associations between K-L grade, pre-operative OKS, age, sex, against change in OKS and Z-OKS were analysed. Results: There were 536 TKR cases, 91 in radiographic sub-group and 360 people in reference cohort. Post-operative Z-OKS was associated with K-L grade (ߠ​= â€‹0.368; p<0.001). Change in OKS was associated with K-L grade (ߠ​= â€‹0.247; p â€‹= â€‹0.003); pre-operative OKS (ߠ​= â€‹-0.449; p<0.001); age (ߠ​= â€‹0.276; p â€‹= â€‹0.001); and female sex protective (ߠ​= â€‹-0.213; p â€‹= â€‹0.008). On average TKR patients returned to 74% of their normative age and sex adjusted OKS, with younger women achieving worst outcomes. More severe radiographic osteoarthritis predicted greater improvement and better post-operative outcome when compared to normative population. Conclusion: This study identified factors and provided normative OKS data intended to guide clinicians in counselling patients regarding likely surgical outcomes. This could help manage patients' expectations, aid decision making and increase post-surgery satisfaction rate.

Prospective analysis of health-related quality of life after surgery for spinal metastases.

PURPOSE: Most spinal metastases are detected late, and thus, the impact of treatment on the health-related quality of life (HRQOL) is an important consideration. This study investigated the HRQOL following surgery for spinal metastases. METHODS: A prospective study of patients operated for symptomatic spinal metastases, at a single tertiary referral spine centre (2011-2013). Data were collected pre-operatively and up to 2 years following surgery (if alive). The HRQOL assessment was performed using recognised systems including the Frankel score (neurological status), EQ-5D, and the Oswestry Disability Index. RESULTS: A total of 199 patients were studied (median age 65 years, 43% (86) F; 57% (113) M). The Frankel score improved significantly after surgery in 69 patients (35%), worsened in 17 (8%), with 20/39 patients regaining the ability to walk (51%). All the HRQOL scores improved significantly following surgery. The complication rate was 27% and median survival 270 days, and 44 patients (22%) survived at 2 years. CONCLUSIONS: This large prospective study showed that surgical treatment for spinal metastases significantly improved the HRQOL.

Does surgical site infection influence neurological outcome and survival in patients undergoing surgery for metastatic spinal cord compression?

PURPOSE: Most of the literature on infection after surgery for spinal metastases focuses on incidence and risk factors for surgical site infection (SSI). To the best of our knowledge, there is no report on the influence of infection on neurological outcome and survival in patients undergoing emergent surgery for metastatic spinal cord compression (MSCC). METHODS: Our aim was to establish if SSIs adversely affected the neurological outcome and survival in patients with MSCC. We reviewed 318 consecutive patients admitted for surgical intervention for MSCC from October 2005 to October 2012. Morbidity (neurological outcome, length of hospital stay and additional procedures) and survival rates were analysed. RESULTS: During this study period, the incidence of infection was 29/318 (9.1%). The median length of stay in hospital in the infected group was 25 days compared to 13 days in the non-infected group (p = 0.001). Twenty out of the 29 (69%) infected patients underwent an additional procedure (29 procedures in total) compared to 9/289 (3%) non-infected patients (p = 0.001). There was no statistical difference between the two groups with regard to neurological outcome (p = 0.37) but the survival rate was statistically different between the two groups [infected group: median survival 131 days (19-1558) vs. non-infected group: 258 days (5-2696; p = 0.03)]. CONCLUSION: Surgical site infection increased the morbidity with considerably longer hospital stay and requirement for additional procedures. Although there was no difference in neurological outcome, the infected group of patients had a significantly shorter survival. These slides can be retrieved under Electronic Supplementary Material.

Latent autoimmune diabetes of adulthood (LADA) is associated with small fibre neuropathy.

AIM: To assess if latent autoimmune diabetes of adulthood (LADA) is associated with small fibre neuropathy. METHODS: Participants with LADA (n=31), Type 2 diabetes (n=31) and healthy control participants without diabetes (n=31) underwent a detailed assessment of neurologic deficits, quantitative sensory testing, electrophysiology, skin biopsy and corneal confocal microscopy. RESULTS: The groups were matched for age (healthy control without diabetes: 53.5±9.1 vs. Type 2 diabetes: 58.0±6.5 vs. LADA: 53.2±11.6 years), duration of diabetes (Type 2 diabetes: 10.0±8.3 vs. LADA: 11.0±9.1 years) and blood pressure. However, BMI (P=0.01) and triglycerides (P=0.0008) were lower and HbA1c (P=0.0005), total cholesterol (P=0.01) and HDL (P=0.002) were higher in participants with LADA compared with Type 2 diabetes. Peroneal motor nerve conduction velocity (P=0.04) and sural sensory nerve conduction velocity (P=0.008) were lower in participants with latent autoimmune diabetes in adults compared with Type 2 diabetes. Intra-epidermal nerve fibre density (P=0.008), corneal nerve fibre density (P=0.003) and corneal nerve branch density (P=0.006) were significantly lower in participants with LADA compared with Type 2 diabetes. There were no significant differences in the other neuropathy parameters. CONCLUSIONS: Despite comparable age and duration of diabetes, participants with LADA demonstrate more severe neuropathy and particularly small fibre neuropathy, compared with participants with Type 2 diabetes.

The effect of exercise on local and systemic adverse reactions after vaccinations - Outcomes of two randomized controlled trials.

INTRODUCTION: An adverse reaction associated with vaccination is considered to be a key barrier to vaccinate, yet little attention has been given to interventions to reduce their occurrence. Exercise is a behavioural adjuvant which may also influence adverse reactions. Here, two randomized controlled trials are reported, examining the effects of exercise on self-reported adverse reactions following vaccination in adolescents and young adults. METHODS: Study one; 116 adolescents receiving the HPV vaccine were randomly allocated to either Control (n = 56) or Pre-vaccine Exercise (n = 60) group (2015-2016). Exercise consisted of 15-minutes upper body exercise. Study two; 78 young adults receiving the influenza vaccine were randomly allocated to either Control (n = 19), or one of 3 exercise groups: Pre-vaccine Arm (n = 19), Pre-vaccine Leg (n = 20) or Post-vaccine Arm (n = 20) (2017). Exercise included 15-minutes of arm or leg exercises prior to or after vaccination. All participants in both studies completed an adverse events diary for seven-days post-vaccination. RESULTS: Study one; Reported days of tenderness in female adolescents that exercised were significantly lower than control (p = 0.032), with a similar trend in reported days of pain (p = 0.050). Furthermore, days of feeling ill (p = 0.070) and reduced appetite (p = 0.067) were found to be lower with exercise, although not significant. Overall, female adolescents reported significantly more days of pain (p = 0.003), tenderness (p < 0.001), swelling (p = 0.011), and feeling ill (p = 0.0040). Study two; Exercise groups reported reduced days of swelling (p = 0.018), fever (p = 0.013), and lowered appetite (p = 0.011) across both genders. Furthermore, females reported reduced days of medication use with exercise (p = 0.034), and a trend toward reduced days of swelling (p = 0.052). DISCUSSION: In two separate trials, a short bout of exercise reduced reported adverse reactions after vaccinations for local and systemic adverse reactions. Gender differences in reported local and systemic adverse reactions were more evident among adolescents than young adults. These findings support the need for further work to examine the potential benefit of exercise in improving vaccination procedures.

The effect of exercise on vaccine-related pain, anxiety and fear during HPV vaccinations in adolescents.

INTRODUCTION: With increased school-based vaccinations for improved coverage rates and practicality, the World Health Organization (WHO) recently endorsed research to identify possible interventions to reduce vaccine-related pain in mass clinical and school-based settings. In particular, the lack of research in adolescents indicate a particular need in this population. Acute exercise has analgesic effects and has been used as a behavioural adjuvant to vaccination. Here, we examine the effect of exercise on vaccine-related pain, anxiety and fear in adolescents, during a school-based program for HPV vaccinations. METHODS: 116 students (Female: 61, Male: 55) aged 11-13 years were randomly allocated to either an Exercise (n = 60) or Control (n = 56) group. All participants completed demographic and Trait-anxiety questionnaires prior to receiving the vaccine according to usual care. The Exercise group also performed upper body exercise for 15 min prior to receiving the vaccine. Immediately after the vaccine administration, all participants reported on pain, anxiety and fear at the time of receiving the vaccine. RESULTS: Female adolescents in the Exercise group reported significantly less pain (3.64; 95% CI, 2.98-4.30) than Controls (4.58; 95% CI, 3.96-5.19; p = 0.04). Further, females reported greater pain and anxiety than males in the Control group but not the Exercise group. CONCLUSION: This study supports the use of exercise prior to vaccine administration, especially in female adolescents who are particularly vulnerable to negative experiences during vaccination procedures. Furthermore, the ease of application, as well as the benefit of exercise, provides support for the use of simple exercise prior to vaccination in mass vaccination settings. Clinical trial registry: ANZCTR, ACTRN12614001185651.

Milk-fat globule epidermal growth factor 8 (MFGE8) is expressed at the embryo- and fetal-maternal interface in equine pregnancy.

Milk-fat globule epidermal growth factor (EGF) 8 protein (MFGE8), also known as lactadherin, promotes cell adhesion in an Arg-Gly-Asp (RGD)-dependent modus via integrins. In the present study, the expression of MFGE8 was examined in equine endometrium during oestrus and at Days 12 and 16 after ovulation in pregnant and non-pregnant mares and in mares during the 5th month of gestation. Results demonstrated that MFGE8 is expressed at the embryo- and fetal-maternal interface in equine pregnancy. In non-pregnant endometrium its expression was upregulated by oestrogen, a finding that was confirmed using endometrial explant culture. MFGE8 was expressed at similar levels by conceptuses collected 13 and 14 days after ovulation and by allantochorion sampled during the 5th month of gestation. Pericytes of endometrial blood vessels displayed strong MFGE8 expression upon in situ hybridisation. During the 5th month of gestation, the fetal side of the allantochorionic villi in particular displayed pronounced staining upon in situ hybridisation, confirming that MFGE8 expression is not restricted to early pregnancy but persists and is present at the fetal-maternal interface. Potential roles of MFGE8 in equine pregnancy include mediating cell-cell adhesion, promotion of angiogenesis and placental transfer of fatty acids.

A reference genome for Nicotiana tabacum enables map-based cloning of homeologous loci implicated in nitrogen utilization efficiency.

BACKGROUND: Tobacco (Nicotiana tabacum) is an important plant model system that has played a key role in the early development of molecular plant biology. The tobacco genome is large and its characterisation challenging because it is an allotetraploid, likely arising from hybridisation between diploid N. sylvestris and N. tomentosiformis ancestors. A draft assembly was recently published for N. tabacum, but because of the aforementioned genome complexities it was of limited utility due to a high level of fragmentation. RESULTS: Here we report an improved tobacco genome assembly, which, aided by the application of optical mapping, achieves an N50 size of 2.17 Mb and enables anchoring of 64% of the genome to pseudomolecules; a significant increase from the previous value of 19%. We use this assembly to identify two homeologous genes that explain the differentiation of the burley tobacco market class, with potential for greater understanding of Nitrogen Utilization Efficiency and Nitrogen Use Efficiency in plants; an important trait for future sustainability of agricultural production. CONCLUSIONS: Development of an improved genome assembly for N. tabacum enables what we believe to be the first successful map-based gene discovery for the species, and demonstrates the value of an improved assembly for future research in this model and commercially-important species.

Do smokers have greater risk of delayed and non-union after fracture, osteotomy and arthrodesis? A systematic review with meta-analysis.

OBJECTIVES: Systematic review and meta-analysis of published observational cohort studies. To quantify the increased risk smokers have of experiencing a delayed and/or non-union in fractures, spinal fusion, osteotomy, arthrodesis or established non-unions. SETTING: Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Allied and Complementary Medicine Database (AMED) and Web of Science Core Collection from 1966 to 2015. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: Observational cohort studies that reported adult smokers and non-smokers with delayed and/or non-union or time to union of the fracture, spinal fusion, osteotomy, arthrodesis or established non-union were eligible. DATA EXTRACTION AND OUTCOME MEASURES: 2 authors screen titles, abstracts and full papers. Data were extracted by 1 author and checked independently by a second. The relative risk ratios of smoking versus non-smoking and the mean difference in time to union patients developing a delayed and/or non-union were calculated. RESULTS: The search identified 3013 articles; of which, 40 studies were included. The meta-analysis of 7516 procedures revealed that smoking is linked to an increased risk of delayed and/or non-union. When considered collectively, smokers have 2.2 (1.9 to 2.6) times the risk of experiencing delayed and/or non-union. In all the subgroups, the increased risk was always ≥1.6 times that of non-smokers. In the patients where union did occur, it was a longer process in the smokers. The data from 923 procedures were included and revealed an increase in time to union of 27.7 days (14.2 to 41.3). CONCLUSIONS: Smokers have twice the risk of experiencing a non-union after fracture, spinal fusion, osteotomy, arthrodesis or treatment of non-union. Time to union following fracture, osteotomy, arthrodesis or treatment of an established non-union is longer in smokers. Smokers should be encouraged to abstain from smoking to improve the outcome of these orthopaedic treatments.

Inferior epigastric artery pseudoaneurysms.

INTRODUCTION: Inferior epigastric artery (IEA) pseudoaneurysms are recognised complications of abdominal wall procedures, and a variety of approaches including surgical excision and ligation, percutaneous procedures and conservative management have been employed in treating this rare complication. METHODS: We describe a case of an IEA pseudoaneurysm diagnosed on computed tomography (CT) angiography, 14 days following a laparoscopic assisted low anterior resection, which was managed successfully with surgical excision and ligation. A review of the literature identified 32 reports of this complication since 1973 with 69% of cases occurring since 2000. FINDINGS: The main aetiology of IEA pseudoaneurysm was abdominal surgery (n=20); 65% of cases were attributable to abdominal wound closure or laparoscopic surgery. Two-thirds (66%) of patients presented between 11 and 63 days, and all except 1 case presented with discomfort, abdominal mass or haemodynamic instability. Colour Doppler ultrasonography was the imaging modality of choice (n=18), either alone or in combination with computed tomography and/or angiography. Surgical ligation and excision and percutaneous coil embolisation formed the mainstay of attempted treatments (69%), particularly following treatment failure using an alternative technique. CONCLUSIONS: The incidence of iatrogenic IEA pseudoaneurysms appears to be increasing. Awareness of this rare complication is of clinical importance to avoid excessive morbidity for affected individuals.

Role of Combined Sentinel Lymph Node Biopsy and Axillary Node Sampling in Clinically Node-Negative Breast Cancer.

Axillary lymph node status is a prognostic marker in breast cancer management, and axillary surgery plays an important role in staging and local control. This study aims to assess whether a combination of sentinel lymph node biopsy (SLNB) using patent blue dye and axillary node sampling (ANS) offers equivalent identification rate to dual tracer technique. Furthermore, we aim to investigate whether there are any potential benefits to this combined technique. Retrospective study of 230 clinically node-negative patients undergoing breast-conserving surgery for single T1-T3 tumours between 2006 and 2011. Axillae were staged using a combined blue dye SLNB/ANS technique. SLNs were localized in 226/230 (identification rate 98.3 %). Three of one hundred ninety-two patients with a negative SLN were found to have positive ANS nodes and 1/4 failed SLNB patients had positive ANS nodes. Thirty-four of two hundred twenty-six patients had SLN metastases and 11/34 (32.4 %) also had a positive non-sentinel lymph node on ANS. Twenty-one of twenty-four (87.5 %) node-positive T1 tumours had single node involvement. Nine of thirty-eight node-positive patients progressed to completion axillary clearance (cALND), and the rest were treated with axillary radiotherapy. Axillary recurrence was nil at median 5 year follow-up. Complementing SLNB with axillary node sampling (ANS) decreases the unavoidable false-negative rate associated with SLNB. Appropriate operator experience and technique can result in an SLN localization rate of 98 %, rivalling a dual tracer technique. The additional insight offered by ANS into the status of non-sentinel nodes has potential applications in an era of less frequent cALND.

Metastatic spinal cord compression as a result of the unknown primary tumour.

PURPOSE: Patients presenting with metastatic spinal cord compression (MSCC) due to an unknown primary tumour (UPT) present an interesting problem with limited literature available to provide guidance on management. Our aim was twofold-first, to analyse all our patients with MSCC due to a UPT pre-operatively, to review their treatment and outcome; second, make comparisons with those patients who presented with MSCC due to a known primary tumour (KPT) during the same period. METHODS: All data was collected retrospectively from October 2004 to October 2009, then prospectively from October 2009 to October 2012 (8 years). We reviewed all patient records held on the database, including patient demographics, primary tumour, neurological outcome (Frankel grade), complications and survival. RESULTS: During the 8-year study period, out of the 382 patients who underwent emergency surgery for MSCC, 285 patients were included in whom complete information was available. Of these, 17 patients presented with MSCC due to a UPT (6 %; mean age 61 years, 5 M, 12 F). When compared to those with a known primary, the UPT group trended to a longer duration of symptoms prior to surgery (200 vs. 156 days, p = 0.86). They had a similar neurological outcome (88 % remained the same or improved post-operatively vs. 90 % in KPT group; p = 0.42), similar complication rate (23.5 vs. 33.6 %; p = 0.32) and survival (222 vs. 251 days, p = 0.42). The primary site in the UPT group was confirmed in 10/17 (58.8 %)-all 10 were adenocarcinoma [lung (6) and GI (4)]. DISCUSSION: In our series, the incidence of MSCC due to an unknown primary was 6 %. They had similar overall outcome (neurology post-operatively, complications and survival) to those patients with MSCC from a known primary. Our experience would suggest that we need to treat these patients expeditiously with thorough evaluation and urgent treatment.

Carbon adsorption onto Fe oxyhydroxide stalks produced by a lithotrophic iron-oxidizing bacteria.

Iron (Fe)-oxidizing bacteria have the potential to produce morphologically unique structures that may be used as biosignatures in geological deposits. One particular example is Mariprofundus ferrooxydans, which produces extracellular twisted ribbon-like stalks consisting of ferrihydrite, co-located with organic and inorganic elements. It is currently thought that M. ferrooxydans excrete and co-precipitate polysaccharides and Fe simultaneously; however, the cellular production of these polysaccharides has yet to be confirmed. Here, we report on a time-series study that used scanning transmission X-ray microscopy and C 1s and Ca 2p near-edge X-ray adsorption fine structure spectroscopy to investigate production of polysaccharides over the growth cycle of M. ferrooxydans. The production and morphology of twisted iron stalks were consistent with previous observations, but unexpectedly, in the log phase, the carbon content of the stalks was extremely low. It was not until stationary growth phase that a significant component of carbon was detected on the stalks. During the log phase, low levels of carbon, only detectable when the stalks were thin, suggested that M. ferrooxydans produce an extracellular polysaccharide template onto which the Fe precipitates. By stationary phase, the increased carbon association with the stalks was a result of adsorption of organic compounds that were released during osmotic shock post-stalk production. In the environment, elevated concentrations of DOC could adsorb onto the Fe stalks as well as a number of other elements, for example, Si, P, Ca, which, by preventing chemical interactions between the Fe nanoparticles, will prevent structural deformation during recrystallization and preserve the structure of these filaments in the rock record.

Effect of timing of surgery on neurological outcome and survival in metastatic spinal cord compression.

PURPOSE: Metastatic spinal cord compression (MSCC) requires expeditious treatment. While there is no ambiguity in the literature about the urgency of care for patients with MSCC, the effect of timing of surgical intervention has not been investigated in detail. The objective of our study was to investigate whether or not the 'timing of surgery' is an important factor in survival and neurological outcome in patients with MSCC. METHODS: All patients with MSCC presenting to our unit from October 2005 to March 2010 were included in this study. Patients were divided into three groups-those who underwent surgery within 24 h (Group 1, n = 45), between 24 and 48 h (Group 2, n = 23) and after 48 h (Group 3, n = 53) from acute presentation of neurological symptoms. The outcome measures studied were neurological outcome (change in Frankel grade post-operatively), survival (survival rate and median survival in days), incidence of infection, length of stay and complications. RESULTS: Patients' age, gender, revised Tokuhashi score, level of spinal metastasis and primary tumour type were not significantly different between the three groups. Greatest improvement in neurology was observed in Group 1, although not significantly when compared against Group 2 (24-48 h; (p = 0.09). When comparisons of neurological outcome were performed for all patients having surgery within 48 h (Groups 1 and 2) versus after 48 h (Group 3), the Frankel grade improvement was significant (p = 0.048) favouring surgery within 48 h of presentation. There was a negative correlation (-0.17) between the delay in surgery and the immediate neurological improvement, suggesting less improvement in those who had delayed surgery. There was no difference in length of hospital stay, incidence of infection, post-operative complications or survival between the groups. CONCLUSIONS: Our results show that surgery should be performed sooner rather than later. Furthermore, earlier surgical treatment within 48 h in patients with MSCC resulted in significantly better neurological outcome. However, the timing of surgery did not influence length of hospital stay, complication rate or patient survival.

Accuracy of the revised Tokuhashi score in predicting survival in patients with metastatic spinal cord compression (MSCC).

PURPOSE: The revised Tokuhashi score has been widely used to evaluate indications for surgery and predict survival in patients with metastatic spinal disease. Our aim was to analyse the actual survival time of patients treated for metastatic spinal cord compression (MSCC) in comparison with the predicted survival based on the revised Tokuhashi score. This would thereby allow us to determine the overall predictive value of this scoring system. METHODS: This study was a semi-prospective clinical study of all patients with MSCC presenting to our unit over 8 years-data from October 2003 to December 2009 were collected retrospectively and from December 2009, all data collected prospectively to October 2011. Patients were divided into three groups--Group 1 (Tokuhashi score 0-8, n = 84), Group 2 (Tokuhashi score 9-11, n = 83) and Group 3 (Tokuhashi score 12-15, n = 34). Data collected included demographic data, primary tumour histology, surgery type and complications, neurological outcome (Frankel grade) and survival. RESULTS: A total of 233 patients with MSCC were managed surgically in our unit during this time. Out of these complete data were available on 201 patients for analysis. Mean age of patients was 61 years (range 18-86; 127 M, 74 F). The primary tumour type was Breast (n = 29, 15 %), Haematological (n = 28, 14 %), Renal (n = 26, 13 %), Prostate (n = 26, 13 %), Lung (n = 23, 11 %), Gastro-intestinal (n = 11, 5 %), Sarcoma (n = 9, 4 %) and others (n = 49, 24 %). All patients included in the study had surgical intervention in the form of decompression and stabilisation. Posterior decompression and stabilisation was performed in 171 patients (with vertebrectomy in 31), combined anterior and posterior approaches were used in 18 patients and 12 had an anterior approach only. The overall complication rate was 19 % (39/201)--the most common being wound infection (n = 15, 8 %). There was no difference in the neurological outcome (Frankel grade) between Groups 1 and 2 (p = 0.34) or Groups 2 and 3 (p = 0.70). However, there was a significant difference between Groups 1 and 3 (p = 0.001), with Group 3 having a significantly better neurological outcome. Median survival was 93 days in Group 1, 229 days in Group 2 and 875 days in Group 3 (p = 0.001). The predictive value between the actual and predicted survival was 64 % (Group 1), 64 % (Group 2) and 69 % (Group 3). The overall predictive value of the revised Tokuhashi score using Cox regression for all groups was 66 %. CONCLUSION: We would conclude that although the predictive value of the Tokuhashi score in terms of survival time is at best modest (66 %), the fact that there were statistically significant differences in survival between the groups looked at in this paper indicates that the scoring system, and the components which it consists of, are important in the evaluation of these patients when considering surgery.

Surgical treatment of cauda equina compression as a result of metastatic tumours of the lumbo-sacral junction and sacrum.

PURPOSE: We performed a retrospective analysis of all cases of lumbo-sacral or sacral metastases presenting with compression of the cauda equina who underwent urgent surgery at our institution. Our objective was to report our experience on the clinical presentation, management and finally the surgical outcome of this cohort of patients. METHODS: We reviewed medical notes and images of all patients with compression of the cauda equina as a result of lumbo-sacral or sacral metastases during the study period (2004-2011). The collected clinical data consisted of time of onset of symptoms, neurology (Frankel grade), ambulatory status and continence. Operative data analysed were details of surgical procedure and complications. Post-operatively, we reviewed neurological outcome, ambulation, continence, destination of discharge and survival. RESULTS: During the 8-year study period, 20 patients [11 males, 9 females; mean age 61.8 years (29-87)] had received urgent surgery for metastatic spinal cauda compression caused by lumbo-sacral or sacral metastases. The majority of patients presented with symptoms of pain and neurological deterioration (n = 14) with onset of pain considerably longer than neurology symptoms [197 days (3-1,825) vs. 46 days (1-540)]; all patients were Frankel C (n = 2, both non-ambulatory), D (n = 13) or E (n = 5) at presentation and three patients were incontinent of urine. Operative procedures performed were posterior decompression with (out) fusion (n = 12), posterior decompression with sacroplasty (n = 1), decompression with lumbo-pelvic stabilisation with (out) kyphoplasty/sacroplasty (n = 7) and posterior decompression/reconstruction with anterior corpectomy/stabilisation (n = 2). Post-operatively, 5/20 (20 %) patients improved one Frankel grade, 1/20 (5 %) improved two grades, 13/20 (65 %) remained stable (8 D, 5 E) and 1/20 (5 %) deteriorated. All patients were ambulatory and 19/20 were continent on discharge. The mean length of stay was 7 days (4-22). There were 6/20 (30 %) complications: three major (PE, deep wound infection, implant failure) and three minor (superficial wound infection, incidental durotomy, chest infection). All patients returned back to their own home (n = 14/20, 70 %) or a nursing home (n = 6/20, 35 %). Thirteen patients are deceased (mean survival 367 days (120-603) and seven are still alive [mean survival 719 days (160-1,719)]. CONCLUSION: Surgical intervention for MSCC involving the lumbo-sacral junction or sacral spine has a high but acceptable complication rate (6/20, 30 %), and can be important in restoring/preserving neurological function, assisting with ambulatory function and allowing patients to return to their previous residence.

In vitro evaluation and biodistribution of HER2-targeted liposomes loaded with an (125)I-labelled DNA-intercalator.

BACKGROUND: Increasing attention is currently focussed on the issue of finding strategies for the delivery of Auger-electron-emitting radionuclides into tumor cell nuclei. PURPOSE: In this study, we investigated tumor-cell uptake and cell-killing ability in vitro as well as in vivo biodistribution of an (125)I-labelled anthracycline derivative administered by means of HER2-targeted liposomes. METHODS: Anthracycline derivative Comp1 was radiolabelled with Auger-emitting (125)I and encapsulated in liposomes (DSPC:Chol:DSPE-PEG) using pH-gradient loading. Single-chain fragment F5 was anchored to the liposomes as targeting device for HER2. Uptake and specificity of (125)I-Comp1 delivered via targeting and non-targeting liposomes were analysed in cultured HER2-overexpressing cells. Cell-killing efficacy was evaluated in SKOV3 cells and biodistribution for up to 48 h was studied after intraperitoneal injection in tumor-bearing female BALB/c nu/nu mice. RESULTS: (125)I-Comp1 was specifically taken up by the cultured cells when administered by means of HER2-targeted liposomes and a clear dose-effect correlation in survival of cells was seen with increasing specific activity. The biodistribution studies revealed that (125)I-Comp1 accumulated in tumors when distributed using HER2-targeted liposomes and that this effect was absent when using non-targeting liposomes. CONCLUSION: The HER2-targeted liposomes possess the properties needed to bring about tumor-specific delivery and therapeutic effect of (125)I-Comp1.

In three brain regions central to maternal behaviour, neither male nor female Phodopus dwarf hamsters show changes in oestrogen receptor alpha distribution with mating or parenthood.

Oestrogen receptor (ER)alpha immunoreactivity in three brain regions relevant to maternal behaviour (medial preoptic area, bed nucleus of the stria terminalis and medial amygdala) was measured in two species of dwarf hamster that both mate during a postpartum oestrous but differ in expression of paternal behaviour. Male and female Phodopus campbelli and Phodopus sungorus were sampled as sexually naive adults, following mating to satiety, and as new parents. In all brain regions, females expressed higher levels of ER alpha than males. Species did not have an effect on ER alpha distribution except in the medial amygdala, where P. sungorus females had higher expression levels than all other groups. Behavioural status was not associated with altered ER alpha expression. These results were not expected for females and suggest that a primary activational role for oestrogen, acting through ER alpha in these regions, does not generalize to maternal behaviour in Phodopus. In males, these results are consistent with previous manipulations of the ER alpha ligand, oestrogen, and suggest that paternal behaviour in P. campbelli is likely to be regulated by developmental effects of oestrogen on the brain during early life (similar to Microtus ochrogaster), rather than through activation by oestrogen at the time of fatherhood (similar to Peromyscus californicus).