Recurrence of low back pain: A difficult outcome to predict. Development and validation of a multivariable prediction model for recurrence in patients recently recovered from an episode of non-specific low back pain.

BACKGROUND: Recurrence of low back pain (LBP) is common. If clinicians could identify an individual's risk of recurrence, this would enhance clinical decision-making and tailored patient care. OBJECTIVE/DESIGN: To develop and validate a simple tool to predict the probability of a recurrence of LBP by 3- or 12-months following recovery. METHODS: Data utilised for the prediction model development came from a prospective inception cohort study of participants (n = 250) recently recovered from LBP, who had sought care from chiropractic or physiotherapy services. The outcome measure was a recurrence of activity-limiting LBP. Candidate predictor variables (e.g., basic demographics, LBP history, levels of physical activity, etc) collected at baseline were considered for inclusion in a multivariable Cox model. The model's performance was tested in a separate validation dataset of participants (n = 261) involved in a randomised controlled trial investigating exercise for the prevention of LBP recurrences. RESULTS: The final model included the number of previous episodes, total sitting time, and level of education. In the development sample, discrimination was acceptable (Harrell's C-statistic = 0.61, 95% CI, 0.59-0.62), but in the validation sample, discrimination was poor (0.56, 95% CI, 0.54-0.58). Calibration of the model in the validation dataset was acceptable at 3 months but was less precise at 12 months. CONCLUSION: The developed prediction model, which included number of previous episodes, total sitting time, and level of education, did not perform adequately in the validation sample to recommend its use in clinical practice. Predicting recurrence of LBP in clinical practice remains challenging.

Convolutional neural networks for the automatic segmentation of lumbar paraspinal muscles in people with low back pain.

The size, shape, and composition of paraspinal muscles have been widely reported in disorders of the cervical and lumbar spine. Measures of size, shape, and composition have required time-consuming and rater-dependent manual segmentation techniques. Convolutional neural networks (CNNs) provide alternate timesaving, state-of-the-art performance measures, which could realise clinical translation. Here we trained a CNN for the automatic segmentation of lumbar paraspinal muscles and determined the impact of CNN architecture and training choices on segmentation performance. T2-weighted MRI axial images from 76 participants (46 female; age (SD): 45.6 (12.8) years) with low back pain were used to train CNN models to segment the multifidus, erector spinae, and psoas major muscles (left and right segmented separately). Using cross-validation, we compared 2D and 3D CNNs with and without data augmentation. Segmentation accuracy was compared between the models using the Sørensen-Dice index as the primary outcome measure. The effect of increasing network depth on segmentation accuracy was also investigated. Each model showed high segmentation accuracy (Sørensen-Dice index ≥ 0.885) and excellent reliability (ICC2,1 ≥ 0.941). Overall, across all muscles, 2D models performed better than 3D models (p = 0.012), and training without data augmentation outperformed training with data augmentation (p < 0.001). The 2D model trained without data augmentation demonstrated the highest average segmentation accuracy. Increasing network depth did not improve accuracy (p = 0.771). All trained CNN models demonstrated high accuracy and excellent reliability for segmenting lumbar paraspinal muscles. CNNs can be used to efficiently and accurately extract measures of paraspinal muscle health from MRI.

Characteristics and Effectiveness of Interventions That Target the Reporting, Communication, or Clinical Interpretation of Lumbar Imaging Findings: A Systematic Review.

BACKGROUND: Patients and clinicians may misinterpret the clinical importance of imaging findings in patients with low back pain, leading to potential harm related to overdiagnosis. PURPOSE: Our aims were to qualitatively summarize the characteristics of tested interventions that target the reporting, communication, or clinical interpretation of lumbar imaging findings and determine whether interventions are effective in improving low back pain-related health outcomes, health care use, or health care costs. DATA SOURCES: PubMed, MEDLINE, CINAHL, EMBASE, PsycINFO, and the Cochrane Library were searched from inception to October 20, 2021. STUDY SELECTION: The search retrieved 4394 articles, nine articles (seven studies) met the inclusion criteria to summarize intervention characteristics. Five of these studies had an adequate design for evaluating intervention effectiveness. DATA ANALYSES: Intervention characteristics were summarized using the Template for Intervention Description and Replication checklist. Effectiveness data were extracted from short, intermediate, and long-term follow-up points. Studies were assessed for risk of bias, and Grading of Recommendations Assessment, Development and Evaluation methodology was used to determine the certainty of the evidence. DATA SYNTHESIS: Four studies investigated the insertion of prevalence information into imaging reports. Single studies investigated withholding diagnostic information, education, and reassurance. Moderate-quality evidence (from 1 study) suggests that inserting prevalence information into imaging reports probably does not change the overall health care use in the long-term but may reduce opioid prescribing. LIMITATIONS: The available evidence is limited, and a meta-analysis was not possible. CONCLUSIONS: Further work is required to develop and test interventions that target the reporting, communication, and clinical interpretation of lumbar imaging findings that may reduce overdiagnosis and improve the management of low back pain.

Use of remote monitoring with continuous glucose monitoring in young children with Type 1 diabetes: the parents' perspective.

AIM: Remote monitoring with continuous glucose monitoring (CGM) in children with Type 1 diabetes mellitus has recently become available, but little is known about caregivers' experiences of its use, particularly in younger children. The aim of this study was to explore parents' everyday experiences of using this technology. METHODS: The parents of children with Type 1 diabetes diagnosed for > 1 year, aged 2-12 years were invited to participate in a semi-structured interview. Interviews were the second phase of a randomized cross-over study using standard insulin therapy with or without CGM and remote monitoring for two 3-month periods. Open-ended questions were used to explore parents' real-life experiences of the remote monitoring and CGM system. Interviews were analysed using thematic analysis. RESULTS: Five themes related to remote monitoring emerged: (i) impact on sleep quality for the parents, (ii) peace of mind, (iii) impact on anxiety, (iv) freedom and confidence for the parents and children, and (v) impact on relationships. Furthermore, parents reported on themes related to CGM in general, such as better understanding of how to manage and control their child's diabetes and experiences related to physical or technical aspects. CONCLUSION: Overall, parents of primary school children reported that using remote monitoring and CGM was a mostly beneficial experience. However, negative aspects within the themes were also reported. These findings will help to provide a structure to discuss parent and child expectations and provide targeted education at the start of using remote monitoring and CGM.

Prospective Comparison of Changes in Lumbar Spine MRI Findings over Time between Individuals with Acute Low Back Pain and Controls: An Exploratory Study.

BACKGROUND AND PURPOSE: The clinical importance of lumbar MR imaging findings is unclear. This study was an exploratory investigation of whether lumbar spine MR imaging findings change more commonly during a 12-week period in individuals with acute low back pain compared with pain-free controls. MATERIALS AND METHODS: Twenty individuals with recent-onset low back pain and 10 pain-free controls were recruited into an exploratory prospective cohort study. All participants had a lumbar spine MR imaging at baseline and repeat MR imaging scans at 1, 2, 6, and 12 weeks. The proportion of individuals who had MR imaging findings that changed during the 12-week period was compared with the same proportion in the controls. RESULTS: In 85% of subjects, we identified a change in at least 1 MR imaging finding during the 12 weeks; however, the proportion was similar in the controls (80%). A change in disc herniation, annular fissure, and nerve root compromise was reported more than twice as commonly in the subjects as in controls (65% versus 30%, 25% versus 10%, and 15% versus 0%, respectively). Caution is required in interpreting these findings due to wide confidence intervals, including no statistical difference. For all other MR imaging findings, the proportions of subjects and controls in whom MR imaging findings were reported to change during 12 weeks were similar. CONCLUSIONS: Changes in MR imaging findings were observed in a similar proportion of the low back pain and control groups, except for herniations, annular fissures, and nerve root compromise, which were twice as common in subjects with low back pain.

Do older adults with chronic low back pain differ from younger adults in regards to baseline characteristics and prognosis?

BACKGROUND: Low back pain (LBP) in older adults is poorly understood because the vast majority of the LBP research has focused on the working aged population. The aim of this study was to compare older adults consulting with chronic LBP to middle aged and young adults consulting with chronic LBP, in terms of their baseline characteristics, and pain and disability outcomes over 1 year. METHODS: Data were systematically collected as part of routine care in a secondary care spine clinic. At initial presentation patients answered a self-report questionnaire and underwent a physical examination. Patients older than 65 were classified as older adults and compared to middle aged (45-65 years old) and younger adults (17-44 years old) for 10 baseline characteristics. Pain intensity and disability were collected at 6 and 12 month follow-ups and compared between age groups. RESULTS: A total of 14,479 participants were included in the study. Of these 3087 (21%) patients were older adults, 6071 (42%) were middle aged and 5321 (37%) were young adults. At presentation older adults were statistically different to the middle aged and younger adults for most characteristics measured (e.g. less intense back pain, more leg pain and more depression); however, the differences were small. The change in pain and disability over 12 months did not differ between age groups. CONCLUSIONS: This study found small baseline differences in older people with chronic LBP compared to middle aged and younger adults. There were no associations between age groups and the clinical course. SIGNIFICANCE: Small baseline differences exist in older people with chronic low back pain compared to middle aged and younger adults referred to secondary care for chronic low back pain. Older adults present with slightly less intense low back pain but slightly more intense leg pain. Changes in pain intensity and disability over a 12 month period were similar across all age groups.

Predicting recovery in patients with acute low back pain: A Clinical Prediction Model.

BACKGROUND: There is substantial variability in the prognosis of acute low back pain (LBP). The ability to identify the probability of individual patients recovering by key time points would be valuable in making informed decisions about the amount and type of treatment to provide. Predicting recovery based on presentation 1-week after initially seeking care is clinically important and may be more accurate than predictions made at initial presentation. The aim of this study was to predict the probability of recovery at 1-week, 1-month and 3-months after 1-week review in patients who still have LBP 1-week after initially seeking care. METHODS: The study sample comprised 1070 patients with acute LBP, with a pain score of ≥2 1-week after initially seeking care. The primary outcome measure was days to recovery from pain. Ten potential prognostic factors were considered for inclusion in a multivariable Cox regression model. RESULTS: The final model included duration of current episode, number of previous episodes, depressive symptoms, intensity of pain at 1-week, and change in pain over the first week after seeking care. Depending on values of the predictor variables, the probability of recovery at 1-week, 1-month and 3-months after 1-week review ranged from 4% to 59%, 19% to 91% and 30% to 97%, respectively. The model had good discrimination (C = 0.758) and calibration. CONCLUSIONS: This study found that a model based on five easily collected variables could predict the probability of recovery at key time points in people who still have LBP 1-week after seeking care. SIGNIFICANCE: A clinical prediction model based on five easily collected variables was able to predict the likelihood of recovery from an episode of acute LBP at three key time points. The model had good discrimination (C = 0.758) and calibration.

Understanding patient beliefs regarding the use of imaging in the management of low back pain.

BACKGROUND: Imaging for low back pain (LBP) remains common despite guidelines recommending against routine imaging. Patient beliefs about imaging may contribute to the problem. This study aimed to quantitatively investigate patient beliefs regarding the need for imaging in managing LBP and to investigate whether personal characteristics, pain characteristics or back pain beliefs are associated with imaging beliefs. METHODS: A survey was performed of consecutive patients presenting to general medical practitioners in Sydney, Australia. Nine medical clinics were selected across varied socioeconomic regions. Survey questions assessed beliefs about the importance of imaging for LBP, collected demographic information, LBP history and general beliefs about back pain. Descriptive statistics and multivariate logistic regression were used to analyse findings. RESULTS: Three hundred completed surveys were collected with a 79.6% response rate. The mean age was 44 years and 60.7% of respondents were women. Exactly, 54.3% (95% CI: 48.7-58.9%) believed that imaging was necessary for the best medical care for LBP. Exactly, 48.0% (95% CI: 42.4-53.6%) believed that everyone with LBP should obtain imaging. Increased age, lower education level, non-European or non-Anglo-saxon cultural background, history of previous imaging and Back Beliefs Questionnaire scores were associated with beliefs that imaging was necessary. CONCLUSION: Approximately, half of all patients presenting to a medical doctor consider low back imaging to be necessary. This may have important implications for overutilization of low back imaging investigations. Knowledge of the factors associated with the patient's belief that imaging is necessary may be helpful in designing appropriate interventions to reduce unnecessary imaging for LBP.

Surface Polysaccharide Mutants Reveal that Absence of O Antigen Reduces Biofilm Formation of Actinobacillus pleuropneumoniae.

Actinobacillus pleuropneumoniae is a Gram-negative bacterium belonging to the Pasteurellaceae family and the causative agent of porcine pleuropneumonia, a highly contagious lung disease causing important economic losses. Surface polysaccharides, including lipopolysaccharides (LPS) and capsular polysaccharides (CPS), are implicated in the adhesion and virulence of A. pleuropneumoniae, but their role in biofilm formation is still unclear. In this study, we investigated the requirement for these surface polysaccharides in biofilm formation by A. pleuropneumoniae serotype 1. Well-characterized mutants were used: an O-antigen LPS mutant, a truncated core LPS mutant with an intact O antigen, a capsule mutant, and a poly-N-acetylglucosamine (PGA) mutant. We compared the amount of biofilm produced by the parental strain and the isogenic mutants using static and dynamic systems. Compared to the findings for the biofilm of the parental or other strains, the biofilm of the O antigen and the PGA mutants was dramatically reduced, and it had less cell-associated PGA. Real-time PCR analyses revealed a significant reduction in the level of pgaA, cpxR, and cpxA mRNA in the biofilm cells of the O-antigen mutant compared to that in the biofilm cells of the parental strain. Specific binding between PGA and LPS was consistently detected by surface plasmon resonance, but the lack of O antigen did not abolish these interactions. In conclusion, the absence of the O antigen reduces the ability of A. pleuropneumoniae to form a biofilm, and this is associated with the reduced expression and production of PGA.

Does the addition of visceral manipulation alter outcomes for patients with low back pain? A randomized placebo controlled trial.

BACKGROUND: This study aimed to investigate whether the addition of visceral manipulation, to a standard physiotherapy algorithm, improved outcomes in patients with low back pain. METHODS: Sixty-four patients with low back pain who presented for treatment at a private physiotherapy clinic were randomized to one of two groups: standard physiotherapy plus visceral manipulation (n = 32) or standard physiotherapy plus placebo visceral manipulation (n = 32). The primary outcome was pain (measured with the 0-10 Numerical Pain Rating Scale) at 6 weeks. Secondary outcomes were pain at 2 and 52 weeks, disability (measured with the Roland-Morris Disability Questionnaire) at 2, 6 and 52 weeks and function (measured with the Patient-Specific Functional Scale) at 2, 6 and 52 weeks. This trial was registered with the Australia and New Zealand Clinical Trials Registry (ACTRN12611000757910). RESULTS: The addition of visceral manipulation did not affect the primary outcome of pain at 6 weeks (-0.12, 95% CI = -1.45 to 1.21). There were no significant between-group differences for the secondary outcomes of pain at 2 weeks or disability and function at 2, 6 or 52 weeks. The group receiving addition of visceral manipulation had less pain than the placebo group at 52 weeks (mean 1.57, 95% CI = 0.32 to 2.82). Participants were adequately blinded to group status and there were no adverse effects reported in either group. CONCLUSIONS: Our study suggests that visceral manipulation in addition to standard care is not effective in changing short-term outcomes but may produce clinically worthwhile improvements in pain at 1 year.

Induction cetuximab, paclitaxel, and carboplatin followed by chemoradiation with cetuximab, paclitaxel, and carboplatin for stage III/IV head and neck squamous cancer: a phase II ECOG-ACRIN trial (E2303).

BACKGROUND: E2303 evaluated cetuximab, paclitaxel, and carboplatin used as induction therapy and concomitant with radiation therapy in patients with stage III/IV head and neck squamous cell carcinoma (HNSCC) determining pathologic complete response (CR), event-free survival (EFS), and toxicity. PATIENTS AND METHODS: Patients with resectable stage III/IV HNSCC underwent induction therapy with planned primary site restaging biopsies (at week 8 in clinical complete responders and at week 14 if disease persisted). Chemoradiation (CRT) began week 9. If week 14 biopsy was negative, patients completed CRT (68-72 Gy); otherwise, resection was carried out. p16 protein expression status was correlated with response/survival. RESULTS: Seventy-four patients were enrolled; 63 were eligible. Forty-four (70%) were free of surgery to the primary site, progression, and death 1-year post-treatment. Following induction, 41 (23 CR) underwent week 8 primary site biopsy and 24 (59%) had no tumor (pathologic CR). Week 14 biopsy during chemoradiation (50 Gy) in 34 (15 previously positive biopsy; 19 no prior biopsy) was negative in 33. Thus 90% of eligible patients completed CRT. Overall survival and EFS were 78% and 55% at 3 years, respectively. Disease progression in 23 patients (37%) was local only in 10 (16%), regional in 5 (8%), local and regional in 2 (3%), and distant in 5 patients (8%). There were no treatment-related deaths. Toxicity was primarily hematologic or radiation-related. p16 AQUA score was not associated with response/survival. CONCLUSIONS: Induction cetuximab, paclitaxel, and carboplatin followed by the same drug CRT is safe and induces high primary site response and promising survival. CLINICAL TRIALS NUMBER: NCT 00089297.

Heritability and lifestyle factors in chronic low back pain: results of the Australian twin low back pain study (The AUTBACK study).

BACKGROUND: Heritability and population-specific lifestyle factors are considered to significantly contribute to chronic low back pain (LBP), but traditional population studies fail to (1) adjust for genetics; and (2) use standard and validated definitions for LBP and for lifestyle factors. METHODS: Using a classical and a co-twin control study design and validated definitions for chronic LBP and lifestyle variables, we explored the relative contribution of genetics and environment on the prevalence of chronic LBP in a sample of adult Australian twins. RESULTS: Data from 105 twin pairs showed that the prevalence of chronic LBP is significantly determined by genetic factors (heritability = 32%). Additionally, monozygotic twins were five times more likely to have chronic LBP than dizygotic twins when one of the siblings of the pair was affected. In a case-control analysis (n = 38 twin pairs), an exploratory analysis showed higher prevalence of chronic LBP associated with light walking exercises and vigorous gardening or heavy work around the house. Daily time spent in sitting was also positively associated with chronic LBP, but not moderate physical activities such as jogging, cycling and gentle swimming. In the final multivariate model, only time spent in vigorous gardening or heavy work around the house remained associated with chronic LBP (odds ratio 6.5; 95% confidence interval 1.47-28.8). CONCLUSIONS: The type, frequency and duration of physical activity may be important to understand risk factors for chronic LBP. The causation path between chronic LBP and people's engagement in activities involving frequent bending and twisting such as gardening and housework should be further investigated.

Predicting rapid recovery from acute low back pain based on the intensity, duration and history of pain: a validation study.

BACKGROUND: Clinical prediction rules can assist clinicians to identify patients with low back pain (LBP) who are likely to recover quickly with minimal treatment; however, there is a paucity of validated instruments to assist with this task. METHOD: We performed a pre-planned external validation study to assess the generalizability of a simple 3-item clinical prediction rule developed to estimate the probability of recovery from acute LBP at certain time points. The accuracy of the rule (calibration and discrimination) was determined in a sample of 956 participants enrolled in a randomized controlled trial. RESULTS: The calibration of the rule was reasonable in the new sample with predictions of recovery typically within 5-10% of observed recovery. Discriminative performance of the rule was poor to moderate and similar to that found in the development sample. CONCLUSIONS: The results suggest that the rule can be used to provide accurate information about expected recovery from acute LBP, within the first few weeks of patients presenting to primary care. Impact analysis to determine if the rule influences clinical behaviours and patient outcomes is required.

Does magnetic resonance imaging predict future low back pain? A systematic review.

BACKGROUND AND OBJECTIVE: Magnetic resonance imaging (MRI) has the potential to identify pathology responsible for low back pain (LBP). However, the importance of findings on MRI remains controversial. We aimed to systematically review whether MRI findings of the lumbar spine predict future LBP in different samples with and without LBP. DATABASES AND DATA TREATMENT: MEDLINE, CINAHL and EMBASE databases were searched. Included were prospective cohort studies investigating the relationship between baseline MRI abnormalities of the lumbar spine and clinically important LBP outcome at follow-up. We excluded cohorts with specific diseases as the cause of their LBP. Associations between MRI findings and LBP pain outcomes were extracted from eligible studies. RESULTS: A total of 12 studies met the inclusion criteria. Six studies presented data on participants with current LBP; one included a sample with no current LBP, three included a sample with no history of LBP and two included mixed samples. Due to small sample size, poor overall quality and the heterogeneity between studies in terms of participants, MRI findings and clinical outcomes investigated, it was not possible to pool findings. No consistent associations between MRI findings and outcomes were identified. Single studies reported significant associations for Modic changes type 1 with pain, disc degeneration with disability in samples with current LBP and disc herniation with pain in a mixed sample. CONCLUSIONS: The limited number, heterogeneity and overall quality of the studies do not permit definite conclusions on the association of MRI findings of the lumbar spine with future LBP (PROSPERO: CRD42012002342).

How is radiating leg pain defined in randomized controlled trials of conservative treatments in primary care? A systematic review.

Many terms exist to describe radiating leg pain or symptoms associated with back pain (e.g., sciatica or radiculopathy) and it appears that these terms are used inconsistently. We examined the terms used to describe, and the eligibility criteria used to define, radiating leg pain in randomized controlled trials of conservative treatments, and evaluated how the eligibility criteria compared to an international pain taxonomy. Eligible studies were identified from two systematic reviews and an updated search of their search strategy. Studies were included if they recruited adults with radiating leg pain associated with back pain. Two independent reviewers screened the studies and extracted data. Studies were grouped according to the terms used to describe radiating leg pain. Thirty-one of the seventy-seven included studies used multiple terms to describe radiating leg pain; the most commonly used terms were sciatica (60 studies) and disc herniation (19 studies). Most studies that used the term sciatica included pain distribution in the eligibility criteria, but studies were inconsistent in including signs (e.g., neurological deficits) and imaging findings. Similarly, studies that used other terms to describe radiating leg pain used inconsistent eligibility criteria between studies and to the pain taxonomy, except that positive imaging findings were required for almost all studies that used disc herniation to describe radiating leg pain. In view of the varying terms to describe, and eligibility criteria to define, radiating leg pain, consensus needs to be reached for each of communication and comparison between studies.

Short term effects of kinesiotaping on acromiohumeral distance in asymptomatic subjects: a randomised controlled trial.

OBJECTIVES: The first aim of this study was to investigate whether kinesiotaping (KT) can increase the acromiohumeral distance (AHD) in asymptomatic subjects in the short term. The second aim was to investigate whether the direction of kinesiotaping application influences AHD. BACKGROUND: In recent years, the use of KT has become increasingly popular for a range of musculoskeletal conditions and for sport injuries. To date, we are unaware of any research investigating the effect of kinesiotaping on AHD. Moreover, it is unknown whether the direction of kinesiotaping application for the shoulder is important. METHODS: Forty nine participants were randomly assigned to one of three groups: kinesiotaping group 1 (KT1), kinesiotaping group 2 (KT2) and sham kinesiotaping (KT3). AHD ultrasound measurements at 0° and 60° of shoulder elevation were collected at baseline and immediately after kinesiotape application. RESULTS: The results showed significant improvements in AHD after kinesiotaping, compared with sham taping. The mean difference in AHD between KT1 and KT3 groups was 1.28 mm (95% CI: 0.55, 2.03), and between KT2 and KT3 was 0.98 mm (95% CI: 0.23, 1.74). Comparison of KT1 and KT2 groups, which was performed to identify whether the direction of taping influences the AHD, indicated there were no significant differences. CONCLUSION: KT increases AHD in healthy individuals immediately following application, compared with sham kinesiotape. No differences were found with respect to the direction in which KT was applied.

Cardioplegic strategies to protect the hypertrophic heart during cardiac surgery.

Cardioplegic arrest and cardiopulmonary bypass are key triggers of myocardial injury during aortic valve surgery. Cardioplegic ischaemic arrest is associated with disruption to metabolic and ionic homeostasis in cardiomyocytes. These changes predispose the heart to reperfusion injury caused by elevated intracellular reactive oxygen species and calcium. Cardiopulmonary bypass is associated with an inflammatory response that can generate systemic oxidative stress which, in turn, provokes further damage to the heart. Techniques of myocardial protection are routinely applied to all hearts, irrespective of their pathology, although different cardiomypathies respond differently to ischaemia and reperfusion injury. In particular, the efficacy of cardioprotective interventions used to protect the hypertrophic heart in patients with aortic valve disease remains controversial. This review will describe key cellular changes in hypertrophy, response to ischaemia and reperfusion and cardioplegic arrest and highlight the importance of optimising cardioprotective strategies to suit hypertrophic hearts.

Increased level of arginase activity correlates with disease severity in HIV-seropositive patients.

Infection with human immunodeficiency virus (HIV) results in a chronic infection that progressively impairs the immune system. Although depletion of CD4(+) T cells is frequently used to explain immunosuppression, chronicity of infection and progressive loss of CD4(+) T cells are not sufficient to fully account for immune dysregulation. Arginase-induced l-arginine deprivation is emerging as a key mechanism for the down-regulation of immune responses. Here, we hypothesized that the level of arginase activity increases with disease severity in HIV-seropositive patients. We determined the levels of arginase activity in peripheral blood mononuclear cells from HIV-seropositive patients and uninfected control participants. Our results show that peripheral blood mononuclear cells from HIV-seropositive patients with low CD4(+) T cell counts expressed statistically significantly higher levels of arginase activity, compared with patients with high CD4(+) T cell counts or uninfected control participants. Furthermore, we found a statistically significant correlation between high level of arginase activity and high viral load in HIV-seropositive patients.

Anti-myelin antibodies modulate clinical expression of childhood multiple sclerosis.

Anti-myelin basic protein (MBP) antibodies in pediatric-onset MS and controls were characterized. Serum samples were obtained from 94 children with MS and 106 controls. Paired CSF and serum were obtained from 25 children with MS at time of their initial episode of acute demyelinating syndrome (ADS). Complementary assays were applied across samples to evaluate the presence, and the physical binding properties, of anti-MBP antibodies. While the prevalence and titers of serum anti-MBP antibodies against both immature and mature forms of MBP were similar in children with MS and in controls, binding characteristics and formal Surface Plasmon Resonance (SPR) studies indicated surprisingly high binding affinities of all pediatric anti-MBP antibodies. Serum levels of anti-MBP antibodies correlated significantly with their CSF levels, and their presence in children with MS was associated with significantly increased risk of an acute disseminated encephalomyelitis-like initial clinical presentation. While antibodies to both immature and mature forms of MBP can be present as part of the normal pediatric humoral repertoire, these anti-myelin antibodies are of surprisingly high affinity, can access the CNS during inflammation, and have the capacity to modulate disease expression. Our findings identify an immune mechanism that could contribute to the observed heterogeneity in spectrum of clinical presentations in early-onset MS.

Systematic review of tests to identify the disc, SIJ or facet joint as the source of low back pain.

Clinical practice guidelines state that the tissue source of low back pain cannot be specified in the majority of patients. However, there has been no systematic review of the accuracy of diagnostic tests used to identify the source of low back pain. The aim of this systematic review was therefore to determine the diagnostic accuracy of tests available to clinicians to identify the disc, facet joint or sacroiliac joint (SIJ) as the source of low back pain. MEDLINE, EMBASE and CINAHL were searched up to February 2006 with citation tracking of eligible studies. Eligible studies compared index tests with an appropriate reference test (discography, facet joint or SIJ blocks or medial branch blocks) in patients with low back pain. Positive likelihood ratios (+LR) > 2 or negative likelihood ratios (-LR) < 0.5 were considered informative. Forty-one studies of moderate quality were included; 28 investigated the disc, 8 the facet joint and 7 the SIJ. Various features observed on MRI (high intensity zone, endplate changes and disc degeneration) produced informative +LR (> 2) in the majority of studies increasing the probability of the disc being the low back pain source. However, heterogeneity of the data prevented pooling. +LR ranged from 1.5 to 5.9, 1.6 to 4.0, and 0.6 to 5.9 for high intensity zone, disc degeneration and endplate changes, respectively. Centralisation was the only clinical feature found to increase the likelihood of the disc as the source of pain: +LR = 2.8 (95%CI 1.4-5.3). Absence of degeneration on MRI was the only test found to reduce the likelihood of the disc as the source of pain: -LR = 0.21 (95%CI 0.12-0.35). While single manual tests of the SIJ were uninformative, their use in combination was informative with +LR of 3.2 (95%CI 2.3-4.4) and -LR of 0.29 (95%CI 0.12-0.35). None of the tests for facet joint pain were found to be informative. The results of this review demonstrate that tests do exist that change the probability of the disc or SIJ (but not the facet joint) as the source of low back pain. However, the changes in probability are usually small and at best moderate. The usefulness of these tests in clinical practice, particularly for guiding treatment selection, remains unclear.