Angiotensinogen and HLA class II predict bevacizumab response in recurrent glioblastoma patients

Background Bevacizumab combination therapy is among the most frequently used treatments in recurrent glioblastoma and patients who achieve response to bevacizumab have improved survival as well as quality of life. Accordingly, the aim of this study was to identify predictive biomarkers for bevacizumab response in recurrent glioblastoma patients. Methods The study included a total of 82 recurrent glioblastoma patients treated with bevacizumab combination therapy whom were both response and biomarker evaluable. Gene expression of tumor tissue was analyzed by using a customized NanoString platform covering 800 genes. Candidate gene predictors associated with response were analyzed by multivariate logistic and Cox regression analysis. Results Two genes were independently associated with response: Low expression of angiotensinogen (2‐fold decrease in AGT; OR = 2.44; 95% CI: 1.45–4.17; P = 0.0009) and high expression of a HLA class II gene (2‐fold increase in HLA‐DQA1; OR = 1.22; 95% CI: 1.01–1.47; P = 0.04). These two genes were included in a model that is able predict response to bevacizumab combination therapy in clinical practice. When stratified for a validated prognostic index, the predictive model for response was significantly associated with improved overall survival. Conclusion Two genes (low angiotensinogen and high HLA‐class II expression) were predictive for bevacizumab response and were included in a predictive model for response. This model can be used in clinical practice to identify patients who will benefit from bevacizumab combination therapy

Physical examination for lumbar radiculopathy due to disc herniation in patients with low-back pain

Background: Low-back pain with leg pain (sciatica) may be caused by a herniated intervertebral disc exerting pressure on the nerve root. Most patients will respond to conservative treatment, but in carefully selected patients, surgical discectomy may provide faster relief of symptoms. Primary care clinicians use patient history and physical examination to evaluate the likelihood of disc herniation and select patients for further imaging and possible surgery. Objectives: (1) To assess the performance of tests performed during physical examination (alone or in combination) to identify radiculopathy due to lower lumbar disc herniation in patients with low-back pain and sciatica; (2) To assess the influence of sources of heterogeneity on diagnostic performance. Search strategy: We searched electronic databases for primary studies: PubMed (includes MEDLINE), EMBASE, and CINAHL, and (systematic) reviews: PubMed and Medion (all from earliest until 30 April 2008), and checked references of retrieved articles. Selection criteria: We considered studies if they compared the results of tests performed during physical examination on patients with back pain with those of diagnostic imaging (MRI, CT, myelography) or findings at surgery. Data collection and analysis: Two review authors assessed the quality of each publication with the QUADAS tool, and extracted details on patient and study design characteristics, index tests and reference standard, and the diagnostic two-by-two table. We presented information on sensitivities and specificities with 95% confidence intervals (95% CI) for all aspects of physical examination. Pooled estimates of sensitivity and specificity were computed for subsets of studies showing sufficient clinical and statistical homogeneity. Main results: We included 16 cohort studies (median N = 126, range 71 to 2504) and three case control studies (38 to100 cases). Only one study was carried out in a primary care population. When used in isolation, diagnostic performance of most physical tests (scoliosis, paresis or muscle weakness, muscle wasting, impaired reflexes, sensory deficits) was poor. Some tests (forward flexion, hyper-extension test, and slump test) performed slightly better, but the number of studies was small. In the one primary care study, most tests showed higher specificity and lower sensitivity compared to other settings. Most studies assessed the Straight Leg Raising (SLR) test. In surgical populations, characterized by a high prevalence of disc herniation (58% to 98%), the SLR showed high sensitivity (pooled estimate 0.92, 95% CI: 0.87 to 0.95) with widely varying specificity (0.10 to 1.00, pooled estimate 0.28, 95% CI: 0.18 to 0.40). Results of studies using imaging showed more heterogeneity and poorer sensitivity. The crossed SLR showed high specificity (pooled estimate 0.90, 95% CI: 0.85 to 0.94) with consistently low sensitivity (pooled estimate 0.28, 95% CI: 0.22 to 0.35). (aut. ref.

Influence of Lamina Terminalis Fenestration on the Occurrence of the Shunt-Dependent Hydrocephalus in Anterior Communicating Artery Aneurysmal Subarachnoid Hemorrhage

Recently, it was reported that fenestration of the lamina terminalis (LT) may reduce the incidence of shunt-dependent hydrocephalus in aneurysmal subarachnoid hemorrhage (SAH). The authors investigated the efficacy of the LT opening on the incidence of shunt-dependent hydrocephalus in the ruptured anterior communicating artery (ACoA) aneurysms. The data of 71-ruptured ACoA aneurysm patients who underwent aneurysmal clipping in acute stage were reviewed retrospectively. Group I (n=36) included the patients with microsurgical fenestration of LT during surgery, Group II (n=35) consisted of patients in whom fenestration of LT was not feasible. The rate of shunt-dependent hydrocephalus was compared between two groups by logistic regression to control for confounding factors. Ventriculo-peritoneal shunts were performed after aneurysmal obliteration in 18 patients (25.4%). The conversion rates from acute hydrocephalus on admission to chronic hydrocephalus in each group were 29.6% (Group I) and 58.8% (Group II), respectively. However, there was no significant correlation between the microsurgical fenestration and the rate of occurrence of shunt-dependent hydrocephalus (p>0.05). Surgeons should carefully decide the concomitant use of LT fenestration during surgery for the ruptured ACoA aneurysms because of the microsurgical fenestration of LT can play a negative role in reducing the incidence of chronic hydrocephalus

Chiropractic and self-care for back-related leg pain: design of a randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Back-related leg pain (BRLP) is a common variation of low back pain (LBP), with lifetime prevalence estimates as high as 40%. Often disabling, BRLP accounts for greater work loss, recurrences, and higher costs than uncomplicated LBP and more often leads to surgery with a lifetime incidence of 10% for those with severe BRLP, compared to 1-2% for those with LBP.</p> <p>In the US, half of those with back-related conditions seek CAM treatments, the most common of which is chiropractic care. While there is preliminary evidence suggesting chiropractic spinal manipulative therapy is beneficial for patients with BRLP, there is insufficient evidence currently available to assess the effectiveness of this care.</p> <p>Methods/Design</p> <p>This study is a two-site, prospective, parallel group, observer-blinded randomized clinical trial (RCT). A total of 192 study patients will be recruited from the Twin Cities, MN (n = 122) and Quad Cities area in Iowa and Illinois (n = 70) to the research clinics at WHCCS and PCCR, respectively.</p> <p>It compares two interventions: chiropractic spinal manipulative therapy (SMT) plus home exercise program (HEP) to HEP alone (minimal intervention comparison) for patients with subacute or chronic back-related leg pain.</p> <p>Discussion</p> <p>Back-related leg pain (BRLP) is a costly and often disabling variation of the ubiquitous back pain conditions. As health care costs continue to climb, the search for effective treatments with few side-effects is critical. While SMT is the most commonly sought CAM treatment for LBP sufferers, there is only a small, albeit promising, body of research to support its use for patients with BRLP.</p> <p>This study seeks to fill a critical gap in the LBP literature by performing the first full scale RCT assessing chiropractic SMT for patients with sub-acute or chronic BRLP using important <b>patient-oriented </b>and <b>objective biomechanical </b>outcome measures.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00494065">NCT00494065</a></p