Cognitive behavioral therapy for the management of multiple sclerosis–related pain: a randomized clinical trial

BACKGROUND: Pain is a common and often debilitating symptom among persons with multiple sclerosis (PwMS). Besides interfering with daily functioning, pain in MS is associated with higher levels of depression and anxiety. While cognitive-behavioral therapy (CBT) for pain has been found to be an effective treatment in other populations, there has been a dearth of research in PwMS. METHODS: PwMS with at least moderate pain severity (N = 20) were randomly assigned to one of two groups: CBT plus standard care (CBT/SC) or MS-related education plus standard care (ED/SC), each of which met for 12 sessions. Changes in pain severity, pain interference, and depressive symptom severity from baseline to the 15 week follow-up were assessed using a 2×2 factorial design. Participants also rated their satisfaction with their treatment and accomplishment of personally meaningful behavioral goals. RESULTS: Both treatment groups rated their treatment satisfaction as very high and their behavioral goals as largely met, although only the CBT/SC group's mean goal accomplishment ratings represented significant improvement. While there were no significant differences between groups post-treatment on the three primary outcomes, there was an overall improvement over time for pain severity, pain interference, and depressive symptom severity. CONCLUSIONS: CBT or education-based programs may be helpful adjunctive treatments for PwMS experiencing pain.Accepted manuscrip

Reduction of freezing of gait in Parkinson's disease by repetitive robot-assisted treadmill training: a pilot study

<p>Abstract</p> <p>Background</p> <p>Parkinson's disease is a chronic, neurodegenerative disease characterized by gait abnormalities. Freezing of gait (FOG), an episodic inability to generate effective stepping, is reported as one of the most disabling and distressing parkinsonian symptoms. While there are no specific therapies to treat FOG, some external physical cues may alleviate these types of motor disruptions. The purpose of this study was to examine the potential effect of continuous physical cueing using robot-assisted sensorimotor gait training on reducing FOG episodes and improving gait.</p> <p>Methods</p> <p>Four individuals with Parkinson's disease and FOG symptoms received ten 30-minute sessions of robot-assisted gait training (Lokomat) to facilitate repetitive, rhythmic, and alternating bilateral lower extremity movements. Outcomes included the FOG-Questionnaire, a clinician-rated video FOG score, spatiotemporal measures of gait, and the Parkinson's Disease Questionnaire-39 quality of life measure.</p> <p>Results</p> <p>All participants showed a reduction in FOG both by self-report and clinician-rated scoring upon completion of training. Improvements were also observed in gait velocity, stride length, rhythmicity, and coordination.</p> <p>Conclusions</p> <p>This pilot study suggests that robot-assisted gait training may be a feasible and effective method of reducing FOG and improving gait. Videotaped scoring of FOG has the potential advantage of providing additional data to complement FOG self-report.</p

Targeting fibroblast activation protein in tumor stroma with chimeric antigen receptor T cells can inhibit tumor growth and augment host immunity without severe toxicity.

The majority of chimeric antigen receptor (CAR) T-cell research has focused on attacking cancer cells. Here, we show that targeting the tumor-promoting, nontransformed stromal cells using CAR T cells may offer several advantages. We developed a retroviral CAR construct specific for the mouse fibroblast activation protein (FAP), comprising a single-chain Fv FAP [monoclonal antibody (mAb) 73.3] with the CD8α hinge and transmembrane regions, and the human CD3ζ and 4-1BB activation domains. The transduced muFAP-CAR mouse T cells secreted IFN-γ and killed FAP-expressing 3T3 target cells specifically. Adoptively transferred 73.3-FAP-CAR mouse T cells selectively reduced FAP(hi) stromal cells and inhibited the growth of multiple types of subcutaneously transplanted tumors in wild-type, but not FAP-null immune-competent syngeneic mice. The antitumor effects could be augmented by multiple injections of the CAR T cells, by using CAR T cells with a deficiency in diacylglycerol kinase, or by combination with a vaccine. A major mechanism of action of the muFAP-CAR T cells was the augmentation of the endogenous CD8(+) T-cell antitumor responses. Off-tumor toxicity in our models was minimal following muFAP-CAR T-cell therapy. In summary, inhibiting tumor growth by targeting tumor stroma with adoptively transferred CAR T cells directed to FAP can be safe and effective, suggesting that further clinical development of anti-human FAP-CAR is warranted

IKK/NF-κB signaling contributes to glioblastoma stem cell maintenance

// Amanda L. Rinkenbaugh 1,2 , Patricia C. Cogswell 2,3 , Barbara Calamini 4 , Denise E. Dunn 4 , Anders I. Persson 5,6 , William A. Weiss 5,6 , Donald C. Lo 4 and Albert S. Baldwin 2 1 Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA 2 Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA 3 Chordoma Foundation, Durham, NC, USA 4 Center for Drug Discovery and Department of Neurobiology, Duke University Medical Center, Durham, NC, USA 5 Helen Diller Family Comprehensive Cancer Center and Department of Neurology, University of California, San Francisco, CA, USA 6 Department of Neurological Surgery and Brain Tumor Research Center, University of California, San Francisco, CA, USA Correspondence to: Albert Baldwin, email: // Keywords : NF-κB, glioblastoma, cancer stem cells, tumor-initiating cells Received : March 14, 2016 Accepted : September 24, 2016 Published : October 06, 2016 Abstract Glioblastoma multiforme (GBM) carries a poor prognosis and continues to lack effective treatments. Glioblastoma stem cells (GSCs) drive tumor formation, invasion, and drug resistance and, as such, are the focus of studies to identify new therapies for disease control. Here, we identify the involvement of IKK and NF-κB signaling in the maintenance of GSCs. Inhibition of this pathway impairs self-renewal as analyzed in tumorsphere formation and GBM expansion as analyzed in brain slice culture. Interestingly, both the canonical and non-canonical branches of the NF-κB pathway are shown to contribute to this phenotype. One source of NF-κB activation in GBM involves the TGF-β/TAK1 signaling axis. Together, our results demonstrate a role for the NF-κB pathway in GSCs and provide a mechanistic basis for its potential as a therapeutic target in glioblastoma

Survival Analysis of Re-resection Versus Radiofrequency Ablation for Intrahepatic Recurrence After Hepatectomy for Hepatocellular Carcinoma

Ó The Author(s) 2011. This article is published with open access at Springerlink.com Background Tumor recurrence after resection of hepatocellular carcinoma is a common phenomenon. Re-resection and radiofrequency ablation (RFA) are good options for treating recurrent HCC. This study compared the efficacy of these two modalities in the treatment of intrahepatic HCC recurrence after hepatectomy. Methods From January 2001 to December 2008, a total of 179 patients developed intrahepatic HCC recurrence after hepatectomy. To treat the recurrence, 29 patients underwent re-resection and 45 patients had RFA. Patient characteristics, clinicopathologic data, and survival outcomes were reviewed. Results Child-Pugh status, time to develop first recurrence (12.2 vs. 8.7 months), and recurrent tumor size (2.1 vs. 2.1 cm) were comparable for the two groups. Time to develop a second intrahepatic recurrence after re-resection and RFA was 5.9 and 4.0 months respectively. The 1-, 3-, and 5-year disease-free survival rates were 41.4%, 24.2%, and 24.2 % after re-resection and 32.2%, 12.4%, and 9.3% after RFA (p = 0.14). The 1-, 3-, and 5-year overall survival rates were 89.7%, 56.5%, and 35.2 % after re-resection and 83.7%, 43.1%, and 29.1 % after RFA (p = 0.48). For the second recurrence, 33.3 % of patients underwent a second round of RFA and 10.0 % underwent a third resection

A powerful and efficient multivariate approach for voxel-level connectome-wide association studies

We describe an approach to multivariate analysis, termed structured kernel principal component regression (sKPCR), to identify associations in voxel-level connectomes using resting-state functional magnetic resonance imaging (rsfMRI) data. This powerful and computationally efficient multivariate method can identify voxel-phenotype associations based on the whole-brain connectivity pattern of voxels, and it can detect linear and non-linear signals in both volume-based and surface-based rsfMRI data. For each voxel, sKPCR first extracts low-dimensional signals from the spatially smoothed connectivities by structured kernel principal component analysis, and then tests the voxel-phenotype associations by an adaptive regression model. The method's power is derived from appropriately modelling the spatial structure of the data when performing dimension reduction, and then adaptively choosing an optimal dimension for association testing using the adaptive regression strategy. Simulations based on real connectome data have shown that sKPCR can accurately control the false-positive rate and that it is more powerful than many state-of-the-art approaches, such as the connectivity-wise generalized linear model (GLM) approach, multivariate distance matrix regression (MDMR), adaptive sum of powered score (aSPU) test, and least-square kernel machine (LSKM). Moreover, since sKPCR can reduce the computational cost of non-parametric permutation tests, its computation speed is much faster. To demonstrate the utility of sKPCR for real data analysis, we have also compared sKPCR with the above methods based on the identification of voxel-wise differences between schizophrenic patients and healthy controls in four independent rsfMRI datasets. The results showed that sKPCR had better between-sites reproducibility and a larger proportion of overlap with existing schizophrenia meta-analysis findings. Code for our approach can be downloaded from https://github.com/weikanggong/sKPCR. [Abstract copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Using Radiological Data to Estimate Ischemic Stroke Severity

Background Risk-adjusted poststroke mortality has been proposed for use as a measure of stroke care quality. Although valid measures of stroke severity (e.g., the National Institutes of Health Stroke Scale [NIHSS]) are not typically available in administrative datasets, radiology reports are often available within electronic health records. We sought to examine whether admission head computed tomography data could be used to estimate stroke severity. Materials and Methods Using chart review data from a cohort of acute ischemic stroke patients (1998-2003), we developed a radiographic measure ([BIS]) of stroke severity in a two-third development set and assessed in a one-third validation set. The retrospective NIHSS was dichotomized as mild/moderate (<10) and severe (≥10). We compared the association of this radiographic score with NIHSS and in-hospital mortality at the patient level. Results Among 1348 stroke patients, 86.5% had abnormal findings on initial head computed tomography. The c-statistic for the BIS for modeling severe stroke (development, .581; validation, .579) and in-hospital mortality (development, .623; validation, .678) were generated. Conclusions Although the c-statistics were only moderate, the BIS provided significant risk stratification information with a 2-variable score. Until administrative data routinely includes a valid measure of stroke severity, radiographic data may provide information for use in risk adjustment

Prevalence, predictors, and outcomes of poststroke falls in acute hospital setting

Abstract—Falls are a serious medical complication following stroke. The objectives of this study were to (1) confirm the prevalence of falls among patients with stroke during acute hospitalization, (2) identify factors associated with falls during the acute stay, and (3) examine whether in-hospital falls were associated with loss of function after stroke (new dependence at discharge). We completed a secondary analysis of data from a retrospective cohort study of patients with ischemic stroke who were hospitalized at one of four hospitals. We used logistic regression to identify factors associated with inpatient falls and examine the association between falls and loss of function. Among 1,269 patients with stroke, 65 (5%) fell during the acute hospitalization period. We found two characteristics independently associated with falls: greater stroke severity (National Institutes of Health Stroke Scale [NIHSS] 8, adjusted odds ratio [OR] = 3.63, 95% confidence interval [CI]: 1.46–9.00) and history of anxiety (adjusted OR = 4.90, 95% CI: 1.70–13.90). Falls were independently associated with a loss of function (adjusted OR = 9.85, 95% CI: 1.22–79.75) even after adjusting for age, stroke severity, gait abnormalities, and past stroke. Stroke severity (NIHSS 8) may be clinically useful during the acute inpatient setting in identifying those at greatest risk of falling. Given the association between falls and poor patient outcomes, rehabilitation interventions should be implemented to prevent falls poststroke

Surveillance of emerging drugs of abuse in Hong Kong: Validation of an analytical tool

© 2015, Hong Kong Academy of Medicine Press. All rights reserved. Objective: To validate a locally developed chromatography-based method to monitor emerging drugs of abuse whilst performing regular drug testing in abusers. Design: Cross-sectional study. Setting: Eleven regional hospitals, seven social service units, and a tertiary level clinical toxicology laboratory in Hong Kong. Participants: A total of 972 drug abusers and high-risk individuals were recruited from acute, rehabilitation, and high-risk settings between 1 November 2011 and 31 July 2013. A subset of the participants was of South Asian ethnicity. In total, 2000 urine or hair specimens were collected. Main outcome measures: Proof of concept that surveillance of emerging drugs of abuse can be performed whilst conducting routine drug of abuse testing in patients. Results: The method was successfully applied to 2000 samples with three emerging drugs of abuse detected in five samples: PMMA (paramethoxymethamphetamine), TFMPP [1-(3-trifluoromethylphenyl)piperazine], and methcathinone. The method also detected conventional drugs of abuse, with codeine, methadone, heroin, methamphetamine, and ketamine being the most frequently detected drugs. Other findings included the observation that South Asians had significantly higher rates of using opiates such as heroin, methadone, and codeine; and that ketamine and cocaine had significantly higher detection rates in acute subjects compared with the rehabilitation population. Conclusions: This locally developed analytical method is a valid tool for simultaneous surveillance of emerging drugs of abuse and routine drug monitoring of patients at minimal additional cost and effort. Continued, proactive surveillance and early identification of emerging drugs will facilitate prompt clinical, social, and legislative management.Link_to_subscribed_fulltex