Outcomes in patients admitted for rehabilitation with spinal cord or cauda equina lesions following degenerative spinal stenosis

Purpose. To evaluate outcome measures and the factors affecting them in patients treated between 1962 and 2000 at Loewenstein Rehabilitation Hospital, Israel.

Method. This retrospective cohort study included 262 patients with spinal neurological lesions (spinal cord or cauda equina lesions) following degenerative spinal stenosis. Data were collected retrospectively. Survival was assessed using the Kaplan-Meier method and the relative mortality risk by the Cox model. Neurological recovery was evaluated by the change in Frankel grades, and factors that affect it were assessed by logistic regression. Associations of length of stay in rehabilitation were analyzed with ANOVA.

Results. Median age at lesion onset was 61 years and median survival 17.6 years. Age at spinal neurological lesion onset was found to be the only factor with a significant effect on survival. Of the 148 patients who had Frankel grades A, B, or C on admission, 58% achieved recovery to grades D and E. Frankel grade at admission, age, and spinal neurological level had a significant effect on recovery. The mean length of stay was 99.7 days, and only Frankel grade had a significant effect on length of stay.

Conclusions. Patients with spinal stenosis and disabling spinal neurological lesions can achieve significant neurological recovery and survive for many years. They require adequate care in a specialist rehabilitation system.     

Ashkenazi Jewish Origin Protects Against Formation of Antibodies to Infliximab and Therapy Failure

Infliximab is an anti-tumor necrosis factor (TNF) used for treatment of inflammatory bowel disease (IBD) as well as rheumatoid arthritis, psoriasis, and other inflammatory conditions. Antibodies to infliximab (ATI) develop in approximately 45% of infliximab-treated IBD patients and are correlated with loss of clinical response. Scarce data exist as to factors which predict infliximab immunogenicity.To investigate factors that may predict formation of antibodies to infliximab (ATI) and infliximab therapy failure an observational study of consecutive IBD patients treated with infliximab between 2009 and 2013 was performed. Trough levels of ATI were measured. Patients were monitored for disease activity using clinical activity indexes and were classified according to ATI formation and clinical response. All clinical and demographic parameters were analyzed for association with the designated outcomes.One hundred fifty-nine patients were included and 1505 sera were tested. On multivariate analysis, Jewish Ashkenazi ethnicity was protective against both development of ATI (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.17–0.7, P = 0.005) and treatment failure (OR 0.29, 95% CI 0.13–0.66, P = 0.003). Concomitant immunomodulator therapy was also negatively associated with immunogenicity and infliximab therapy failure (OR 0.31, 95% CI 0.15–0.65, P = 0.002; OR 0.42 95% CI 0.18−0.99, p = 0.04, respectively), whereas episodic therapy was positively associated with both outcomes (OR 4.2 95% CI 1.07−16.1, p = 0.04, OR 4.45 95% CI 1.2−16.6, p = 0.026 respectively). All other variables, including IBD type, gender, weight, age, smoking status and disease duration, were not predictive of ATI formation or clinical failure. However, among Crohn''s disease patients, a non-stricturing non-penetrating phenotype was protective against ATI formation (OR 0.4, 95% CI 0.14−0.96, p = 0.04). P = 0.04, respectively), whereas episodic/interrupted therapy was positively associated with both outcomes (OR 4.2, 95% CI 1.07–16.1, P = 0.04; OR 4.45, 95% CI 1.2–16.6, P = 0.026, respectively). All other variables, including IBD type, sex, weight, age, smoking status, and disease duration, were not predictive of ATI formation or clinical failure. However, among Crohn disease patients, a nonstricturing nonpenetrating phenotype was protective against ATI formation (OR 0.4, 95% CI 0.14–0.96, P = 0.04).Jewish Ashkenazi ethnicity is protective of ATI formation and infliximab therapy failure. These findings suggest a role for ethnicity, and implicitly for genetic predisposition, in modulating the risk of anti-TNF immunogenicity and treatment unresponsiveness.     

Decorrelation of retinal response to natural scenes by fixational eye movements

Under natural viewing conditions the input to the retina is a complex spatiotemporal signal that depends on both the scene and the way the observer moves. It is commonly assumed that the retina processes this input signal efficiently by taking into account the statistics of the natural world. It has recently been argued that incessant microscopic eye movements contribute to this process by decorrelating the input to the retina. Here we tested this theory by measuring the responses of the salamander retina to stimuli replicating the natural input signals experienced by the retina in the presence and absence of fixational eye movements. Contrary to the predictions of classic theories of efficient encoding that do not take behavior into account, we show that the response characteristics of retinal ganglion cells are not sufficient in themselves to disrupt the broad correlations of natural scenes. Specifically, retinal ganglion cells exhibited strong and extensive spatial correlations in the absence of fixational eye movements. However, the levels of correlation in the neural responses dropped in the presence of fixational eye movements, resulting in effective decorrelation of the channels streaming information to the brain. These observations confirm the predictions that microscopic eye movements act to reduce correlations in retinal responses and contribute to visual information processing.Much effort has been devoted to understanding how the neural code of the retina and downstream neurons can represent visual information efficiently given the statistical structure of the natural world (1–6). Although these theories have contributed tremendously to current understanding of early visual processing, they do not consider the observer’s motor activity but rather rely on the simplifying assumption that the input to the retina is a stationary image. However, even during fixation on a single point, small movements of the eye, head, and other parts of the body continually modulate visual input signals. Experiments have shown that elimination of retinal image motion leads to fading of vision (7, 8). Therefore, eye movements are essential for the normal functioning of the visual system.It has been proposed that, rather than simply preventing adaptation in neural responses, fixational eye movements are a critical stage of information processing, in which predictable spatial correlations are discarded to enable encoding of luminance discontinuities by synchronous neural activity (9, 10). Thus, fixational eye movements counterbalance the spectral density of natural scenes and yield temporal modulations with equalized power over a broad range of spatial frequencies. Because spectral equalization is equivalent to decorrelation in space, this theory predicts that fixational eye movements should attenuate correlations in the responses of the retinal ganglion cells. Modeling results have provided support to this hypothesis (9, 10).     

International, multicenter, randomized, controlled study comparing dynamically individualized versus standard treatment in patients with chronic hepatitis C

BACKGROUND/AIMS: The aim of this study was to increase virologic response rates by individualized treatment according to the early virologic response. METHODS: Serum HCV-RNA was frequently quantified in patients with chronic hepatitis C (n=270) treated with peginterferon alfa-2a (180 microg/week) and ribavirin (1000-1200 mg/day). After 6 weeks patients were classified as rapid (RVR), slow (SPR), flat (FPR), or null responders (NUR) and randomized within each viral kinetic class to continue therapy either with an individualized or standard regimen. Individualized therapy comprised peginterferon monotherapy (48 weeks) or shorter combination therapy (24 weeks) for RVR, triple therapy with histamine (1 mg/day) (48 weeks) or prolonged combination therapy (72 weeks) for SPR, triple therapy for FPR, and high-dose peginterferon (360 microg/week) plus ribavirin for NUR patients. RESULTS: Patients were categorized as RVR (n=171), SPR (n=65), FPR (n=10), or NUR (n=22). Overall end-of-treatment and sustained virologic response rates were 77 and 60% in the individualized and 77 and 66% in the standard treatment arm, respectively. Histamine in addition to peginterferon and ribavirin and high-dose peginterferon plus ribavirin did not improve virologic response rates in patients with FPR and NUR, respectively. CONCLUSIONS: An improvement in virologic efficacy was not achieved with the available individualized treatment options.