Lesions in the Posterior Visual Pathway Promote Trans-Synaptic Degeneration of Retinal Ganglion Cells

Objective

Retrograde trans-synaptic degeneration of retinal ganglion cell layer (GCL) has been proposed as one of the mechanisms contributing to permanent disability after visual pathway damage. We set out to test this mechanism taking advantage of the new methods for imaging the macula with high resolution by optical coherence tomography (OCT) in patients with lesions in the posterior visual pathway. Additionally, we explored the association between thinning of GCL as an imaging marker of visual impairment such as visual field defects.

Methods

Retrospective case note review of patients with retrogeniculate lesions studied by spectral domain OCT of the macula and quadrant pattern deviation (PD) of the visual fields.

Results

We analysed 8 patients with either hemianopia or quadrantanopia due to brain lesions (stroke  = 5; surgery  = 2; infection  = 1). We found significant thinning of the GCL in the projecting sector of the retina mapping to the brain lesion. Second, we found strong correlation between the PD of the visual field quadrant and the corresponding macular GCL sector for the right (R = 0.792, p<0.001) and left eyes (R = 0.674, p<0.001).

Conclusions

The mapping between lesions in the posterior visual pathway and their projection in the macula GCL sector corroborates retrograde trans-synaptic neuronal degeneration after brain injury as a mechanism of damage with functional consequences. This finding supports the use of GCL thickness as an imaging marker of trans-synaptic degeneration in the visual pathway after brain lesions.     

Progressive Levels of Physical Dependence to Tobacco Coincide with Changes in the Anterior Cingulum Bundle Microstructure

Background

The tobacco withdrawal syndrome indicates the development of neurophysiologic dependence. Clinical evidence indicates that neurophysiologic dependence develops through a set sequence of symptom presentation that can be assessed with a new 3-item survey measure of wanting, craving, and needing tobacco, the Level of Physical Dependence (PD). This study sought to determine if advancing neurophysiologic dependence as measured by the Level of PD correlates with characteristics of white matter structure measured by Fractional Anisotropy (FA).

Methods

Diffusion-MRI based FA and diffusion tensor imaging probabilistic tractography were used to evaluate 11 smokers and 10 nonsmokers. FA was also examined in relation to two additional measures of dependence severity, the Hooked on Nicotine Checklist (HONC), and the Fagerström Test for Nicotine Dependence (FTND).

Results

Among smokers, FA in the left anterior cingulate bundle (ACb) correlated negatively with the Level of PD (r = −0.68, p = 0.02) and HONC scores (r = −0.65, p = 0.03), but the correlation for the FTND did not reach statistical significance (r = −49, p = 0.12). With advancing Levels of PD, the density of streamlines between the ACb and precuneus increased (r = −0.67, p<0.05) and those between the ACb and white matter projecting to the superior-frontal cortex (r = −0.86, p = 0.0006) decreased significantly.

Conclusions

The correlations between neural structure and both the clinical Level of PD survey measure and the HONC suggest that the Level of PD and the HONC may reflect the microstructural integrity of white matter, as influenced by tobacco abuse. Given that the Level of PD is measuring a sequence of symptoms of neurophysiologic dependence that develops over time, the correlation between the Level of PD and neural structure suggests that these features might represent neuroplastic changes that develop over time to support the development of neurophysiologic dependence.     

Photoacoustic Imaging of Breast Microcalcifications: A Preliminary Study with 8-Gauge Core-Biopsied Breast Specimens

Background

We presented the photoacoustic imaging (PAI) tool and to evaluate whether microcalcifications in breast tissue can be detected on photoacoustic (PA) images.

Methods

We collected 21 cores containing microcalcifications (n = 11, microcalcification group) and none (n = 10, control group) in stereotactic or ultrasound (US) guided 8-gauge vacuum-assisted biopsies. Photoacoustic (PA) images were acquired through ex vivo experiments by transmitting laser pulses with two different wavelengths (700 nm and 800 nm). The presence of microcalcifications in PA images were blindly assessed by two radiologists and compared with specimen mammography. A ratio of the signal amplitude occurring at 700 nm to that occurring at 800 nm was calculated for each PA focus and was called the PAI ratio.

Results

Based on the change of PA signal amplitude between 700 nm and 800 nm, 10 out of 11 specimens containing microcalcifications and 8 out of 10 specimens without calcifications were correctly identified on blind review; the sensitivity, specificity, accuracy, positive predictive and negative predictive values of our blind review were 90.91%, 80.0%, 85.71%, 83.33% and 88.89%. The PAI ratio in the microcalcification group was significantly higher than that in the control group (the median PAI ratio, 2.46 versus 1.11, respectively, P = .001). On subgroup analysis in the microcalcification group, neither malignant diagnosis nor the number or size of calcification-foci was proven to contribute to PAI ratios.

Conclusion

Breast microcalcifications generated distinguishable PA signals unlike breast tissue without calcifications. So, PAI, a non-ionizing and non-invasive hybrid imaging technique, can be an alternative in overcoming the limitations of conventional US imaging.     

Is R2* a New MRI Biomarker for the Progression of Parkinson’s Disease? A Longitudinal Follow-Up

Purpose

To study changes of iron content in basal ganglia in Parkinson’s disease (PD) through a three-year longitudinal follow-up of the effective transverse relaxation rate R₂*, a validated MRI marker of brain iron content which can be rapidly measured under clinical conditions.

Methods

Twenty-seven PD patients and 26 controls were investigated by a first MRI (t₀). Longitudinal analysis was conducted among the 18 controls and 14 PD patients who underwent a second MRI (t₁) 3 years after. The imaging protocol consisted in 6 gradient echo images obtained at different echo-times for mapping R₂*. Quantitative exploration of basal ganglia was performed by measuring the variation of R₂* [R₂*(t₁) – R₂*(t₀)] in several regions of interest.

Results

During the three-year evolution of PD, R₂* increased in Substantia nigra (SN) (by 10.2% in pars compacta, p = 0.001, and 8.1% in pars reticulata, p = 0.013) and in the caudal putamen (11.4%, p = 0.011), without significant change in controls. Furthermore, we showed a positive correlation between the variation of R₂* and the worsening of motor symptoms of PD (p = 0.028).

Conclusion

Significant variation of R₂* was longitudinally observed in the SN and caudal putamen of patients with PD evolving over a three-year period, emphasizing its interest as a biomarker of disease progression. Our results suggest that R₂* MRI follow-up could be an interesting tool for individual assessment of neurodegeneration due to PD, and also be useful for testing the efficiency of disease-modifying treatments.     

A Meta-Analysis of Randomised Placebo-Controlled Treatment Trials for Depression and Anxiety in Parkinson’s Disease

Background

Psychopharmacotherapy currently constitutes the first-line treatment for depression and anxiety in Parkinson’s disease (PD) however the efficacy of antidepressant treatments in PD is unclear. Several alternative treatments have been suggested as potentially more viable alternatives including dopamine agonists, repetitive transcranial magnetic stimulation, and cognitive behavioural therapy (CBT).

Method

A meta-analysis of randomised placebo-controlled trials for depression and/or anxiety in PD was conducted to systematically examine the efficacy of current treatments for depression and anxiety in PD.

Results

Nine trials were included. There was only sufficient data to calculate a pooled effect for antidepressant therapies. The pooled effect of antidepressants for depression in PD was moderate but non-significant (d = .71, 95% CI = −1.33 to 3.08). The secondary effect of antidepressants on anxiety in PD was large but also non-significant (d = 1.13, 95% CI = −.67 to 2.94). Two single-trials of non-pharmacological treatments for depression in PD resulted in significant large effects; Omega-3 supplementation (d = .92, 95% CI = .15 to 1.69) and CBT (d = 1.57, 95% CI = 1.06 to 2.07), and warrant further exploration.

Conclusions

There remains a lack of controlled trials for both pharmacological and non-pharmacological treatments for depression and anxiety in PD which limits the conclusions which can be drawn. While the pooled effects of antidepressant therapies in PD were non-significant, the moderate to large magnitude of each pooled effect is promising. Non-pharmacological approaches show potential for depression in PD however more research is required.     

Aerobic Exercise for Parkinson's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

Although some trials assessed the effectiveness of aerobic exercise for Parkinson''s disease (PD), the role of aerobic exercise in the management of PD remained controversial.

Objective

The purpose of this systematic review is to evaluate the evidence about whether aerobic exercise is effective for PD.

Methods

Seven electronic databases, up to December 2013, were searched to identify relevant studies. Two reviewers independently extracted data and assessed methodological quality based on PEDro scale. Standardised mean difference (SMD) and 95% confidence intervals (CI) of random-effects model were calculated. And heterogeneity was assessed based on the I² statistic.

Results

18 randomized controlled trials (RCTs) with 901 patients were eligible. The aggregated results suggested that aerobic exercise should show superior effects in improving motor actions (SMD, −0.57; 95% CI −0.94 to −0.19; p = 0.003), balance (SMD, 2.02; 95% CI 0.45 to 3.59; p = 0.01), and gait (SMD, 0.33; 95% CI 0.17 to 0.49; p<0.0001) in patients with PD, but not in quality of life (SMD, 0.11; 95% CI −0.23 to 0.46; p = 0.52). And there was no valid evidence on follow-up effects of aerobic exercise for PD.

Conclusion

Aerobic exercise showed immediate beneficial effects in improving motor action, balance, and gait in patients with PD. However, given no evidence on follow-up effects, large-scale RCTs with long follow-up are warrant to confirm the current findings.     

Occupational Complexity and Risk of Parkinson's Disease

Background

The etiology of Parkinson''s disease (PD) remains unclear, and environmental risk-factors such as occupation have attracted interest.

Objective

The goal was to investigate occupational complexity in relation to PD.

Methods

We conducted a population-based cohort study based on the Swedish Twin Registry that included 28,778 twins born between 1886 and 1950. We identified 433 PD cases during the study period. Data on occupation were collected from either the 1970 or 1980 Swedish census, and occupational complexity was assessed via a job exposure matrix. Cox proportional hazard regression analyses with age as the underlying time scale were used to assess PD risk as a function of the three domains of occupational complexity: data, people, and things. Sex and smoking were included as covariates. Analyses stratified by twin pair were conducted to test for confounding by familial factors.

Results

High occupational complexity with data and people was associated with increased risk overall (Hazard Ratio [HR] = 1.07, 95% confidence interval [CI] 1.02–1.14, and HR = 1.10, 95% CI 1.01–1.21, respectively), and in men (HR = 1.08, 95% CI 1.01–1.16, and HR = 1.15, 95% CI 1.03–1.28, respectively). Complexity with things was not associated with risk of PD. When the analyses were stratified by twin pair, the HRs for occupational complexity with data and people were attenuated in men.

Conclusions

High complexity of work with data and people is related to increased risk of PD, particularly in men. The attenuation of risk observed in the twin pair-stratified analyses suggests that the association may partly be explained by familial factors, such as inherited traits contributing to occupational selection or other factors shared by twins.     

Factors Influencing Turning and Its Relationship with Falls in Individuals with Parkinson’s Disease

Background

Falls are a major problem for people with Parkinson’s disease (PD). Many studies indicate that more than 50% of people with PD have difficulty in turning that may lead to falls during daily activities. The aims of this study were to identify the relationship between turning performance and falls, and to determine the factors that influence turning performance.

Methods

This study examined 45 patients with idiopathic PD (Hoehn and Yahr stage 1–3) using a battery of tests, including 180° turn time, balance, and muscle strength. The levels of disease severity and freezing of gait were also measured. The number of falls in the past 6 months was recorded.

Results

Sixteen out of forty-five participants experienced falls in the past 6 months. A receiver operating characteristic curve showed that turn time was highly related to falls [more affected side: sensitivity = 0.81, specificity = 0.79, area under the curve (AUC) = 0.83; less affected side: sensitivity = 0.88, specificity = 0.76, AUC = 0.83]. The most important factor influencing turn time was balance ability (both sides: p = 0.000) according to the regression model. Correlations between turn time and dynamic balance were further established with reaction time, movement velocity, endpoint excursion, and maximal excursion of the LOS (limits of stability) test.

Conclusion

The time needed to complete a 180° turn during the SQT (step/quick turn) test is a good index to differentiate fallers from non-fallers in persons with PD. Turn time is most influenced by balance. Furthermore, balance control, especially in an anterior or sideways direction, is important for turning performance.     

Histological Criteria for Encapsulating Peritoneal Sclerosis – A Standardized Approach

Background

The two most relevant pathologies of long-term peritoneal dialysis (PD) are simple sclerosis and encapsulating peritoneal sclerosis (EPS). The histological differentiation of those two entities is difficult. The Aim of the study was to establish a method to standardize and facilitate the differentiation between simple sclerosis and EPS

Methods

We investigated 58 peritoneal biopsies - 31 EPS patients and 27 PD patients. Two blinded investigators analyzed 20 histological characteristics in EPS and PD patients.

Results

The following findings were significantly more common in EPS than in patients on PD without EPS: fibroblast like cells (FLC) (p<0.0001), mesothelial denudation (p<0.0001), decreased cellularity (p = 0.008), fibrin deposits (p<0.03), Fe deposits (p = 0.05), podoplanin vascular (p<0.0001), podoplanin avascular (p<0.0001). Using all predictor variables we trained the classification method Random Forest to categorize future cases. Podoplanin vascular and avascular were taken together (p<0.0001), FLC (p<0.0001), mesothelial denudation (p = 0.0005), calcification (p = 0.0026), acellular areas (p = 0.0094), and fibrin deposits (p = 0.0336) showed up as significantly important predictor variables. Estimated misclassification error rate when classifying new cases turned out to be 14%.

Conclusion

The introduced statistical method allows discriminating between simple sclerosis and EPS. The misclassification error will likely improve with every new case added to the database.     

Predictors of Two Months Culture Conversion in Multidrug-Resistant Tuberculosis: Findings from a Retrospective Cohort Study

Background

Various studies have reported culture conversion at two months as a predictor of successful treatment outcome in multidrug-resistant tuberculosis (MDR-TB).

Objectives

The present study was conducted with the aim to evaluate the rate and predictors of culture conversion at two months in MDR-TB patients.

Methods

All confirmed pulmonary MDR-TB patients enrolled for treatment at Lady Reading Hospital Peshawar, Pakistan from 1 January to 31 December 2012 and met the inclusion criteria were reviewed retrospectively. Rate and predictors of culture conversion at two months were evaluated.

Results

Eighty seven (53.4%) out of 163 patients achieved culture conversion at two months. In a multivariate analysis lung cavitation at baseline chest X-ray (P = 0.006, OR = 0.349), resistance to ofloxacin (P = 0.041, OR = 0.193) and streptomycin (P = 0.017, OR = 0.295) had statistically significant (P<0.05) negative association with culture conversion at two months.

Conclusion

A reasonable proportion of patients achieved culture conversion at two months. Factors negatively associated with culture conversion at two months can be easily identified either before diagnosis or early in the course of MDR-TB treatment. This may help in better care of individual patients by identifying them early and treating them vigorously.     

Meta-Analysis: Narrow Band Imaging for Diagnosis of Gastric Intestinal Metaplasia

Background

Distinguishing early gastric cancer is challenging with current imaging techniques. Narrow band imaging (NBI) is effective for characterizing gastric lesions.

Objectives

The aim of this meta-analysis was to estimate the diagnostic accuracy of NBI in the gastric intestinal metaplasia (GIM).

Methods

We performed data analysis using Meta-DiSc (version 1.4) and STATA (version 11.0) software. To assess study quality and potential for bias, we used the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool.

Results

Six studies involving 347 patients were included. On a per-patient basis, the sensitivity of NBI for diagnosis of GIM was 0.65 (95% CI  =  0.56–0.74), and the specificity was 0.93 (95% CI  =  0.88–0.97). The area under the summary receiver operating characteristic (SROC) curve was 0.8731. However, on a per-lesion basis, the sensitivity and specificity of NBI were 0.69 (95% CI  =  0.63–0.74) and 0.91 (95% CI  =  0.87–0.94), respectively. The SROC was 0.9009. The pooled sensitivity and specificity of magnification endoscopy (NBI-ME) were 0.76 (95% CI  =  0.61–0.87) and 0.89 (95% CI  =  0.80–0.94), respectively, on per-patient analysis. On a per-lesion basis, the pooled sensitivity and specificity of NBI-ME were 0.84 (95% CI  =  0.76–0.89) and 0.93 (95% CI  =  0.89–0.96), respectively. Heterogeneity was observed with an I² for diagnostic odds ratio (DOR) of 0.01% and 85.8%, respectively. There was no statistical significance for the evaluation of publication bias.

Conclusions

Our meta-analysis shows that NBI is a useful tool for differential diagnosis of GIM with relatively low sensitivity and high specificity.     

Predictors of Seizure Outcomes in Children with Tuberous Sclerosis Complex and Intractable Epilepsy Undergoing Resective Epilepsy Surgery: An Individual Participant Data Meta-Analysis

Objective

To perform a systematic review and individual participant data meta-analysis to identify preoperative factors associated with a good seizure outcome in children with Tuberous Sclerosis Complex undergoing resective epilepsy surgery.

Data Sources

Electronic databases (MEDLINE, EMBASE, CINAHL and Web of Science), archives of major epilepsy and neurosurgery meetings, and bibliographies of relevant articles, with no language or date restrictions.

Study Selection

We included case-control or cohort studies of consecutive participants undergoing resective epilepsy surgery that reported seizure outcomes. We performed title and abstract and full text screening independently and in duplicate. We resolved disagreements through discussion.

Data Extraction

One author performed data extraction which was verified by a second author using predefined data fields including study quality assessment using a risk of bias instrument we developed. We recorded all preoperative factors that may plausibly predict seizure outcomes.

Data Synthesis

To identify predictors of a good seizure outcome (i.e. Engel Class I or II) we used logistic regression adjusting for length of follow-up for each preoperative variable.

Results

Of 9863 citations, 20 articles reporting on 181 participants were eligible. Good seizure outcomes were observed in 126 (69%) participants (Engel Class I: 102(56%); Engel class II: 24(13%)). In univariable analyses, absence of generalized seizure semiology (OR = 3.1, 95%CI = 1.2–8.2, p = 0.022), no or mild developmental delay (OR = 7.3, 95%CI = 2.1–24.7, p = 0.001), unifocal ictal scalp electroencephalographic (EEG) abnormality (OR = 3.2, 95%CI = 1.4–7.6, p = 0.008) and EEG/Magnetic resonance imaging concordance (OR = 4.9, 95%CI = 1.8–13.5, p = 0.002) were associated with a good postoperative seizure outcome.

Conclusions

Small retrospective cohort studies are inherently prone to bias, some of which are overcome using individual participant data. The best available evidence suggests four preoperative factors predictive of good seizure outcomes following resective epilepsy surgery. Large long-term prospective multicenter observational studies are required to further evaluate the risk factors identified in this review.     

Potential Usefulness of FDG PET/CT in Patients with Sepsis of Unknown Origin

Purpose

The role of FDG PET in the evaluation of patients with sepsis of unknown origin remains unclear. We sought to assess the value of FDG PET/CT in patients with sepsis of unknown cause and to define its priority in this group of subjects.

Methods

A total of 53 patients with sepsis of unknown origin underwent FDG PET/CT within two weeks of diagnosis. All of the patients were followed up for at least 3 months after discharge to determine the clinical outcomes. The impact of FDG PET/CT was assessed according to the number of cases who had their treatment modified on the basis of the imaging results. Logistic regression analysis was used to identify the independent predictors of positive FDG PET/CT findings.

Results

Of the 53 study patients, 35 (66%) had positive FDG PET/CT findings, and 13 (25%) had their treatment modified on the basis of the imaging results. Logistic regression analysis identified normal serum aspartate aminotransferase (odds ratio [OR]  = 6.134; 95% confidence interval [CI]  = 1.443–26.076, P = 0.014) and increased serum alkaline phosphatase levels (OR = 5.813; 95% CI = 1.386–24.376, P = 0.016) at diagnosis as independent predictors of positive FDG PET/CT findings. A scoring system using these two covariates was developed, which defined three distinct priority groups for FDG PET/CT imaging.

Conclusion

Our findings suggest that FDG PET/CT may be clinically useful for the detection of occult foci of infection in patients with sepsis of unknown origin.     

Eradication of Helicobacter pylori Infection Improves Levodopa Action,Clinical Symptoms and Quality of Life in Patients with Parkinson's Disease

Background

Previous studies have demonstrated a higher prevalence of Helicobacter pylori (H. pylori) infection in patients with Parkinson''s disease (PD) compared to controls. H. pylori infection affects levodopa absorption and its eradication significantly improves clinical response to levodopa. Here, we studied the prevalence of H. pylori infection and its eradication effects among our PD patients.

Methods

A prospective study involving idiopathic PD patients on levodopa therapy. ¹³C-urea breath test (UBT) was used to detect H. pylori. UBT-positive patients were given standard eradication therapy and followed up at 6 and 12 weeks in an open label single arm design. Repeat UBT was performed at 12 weeks. The UPDRS, PD NMQ, PD NMSS and PDQ-39 were administered at baseline and post-eradication (6 and 12 weeks). Levodopa ‘onset’ time and ON-duration were recorded.

Results

Of 82 patients recruited, 27 (32.9%) had positive UBT. H. pylori-positive patients had significantly poorer total UPDRS (p = 0.005) and PDQ39 (p<0.0001) scores compared to H. pylori-negative patients. At 12 weeks post-eradication, the mean levodopa onset time shortened by 14 minutes (p = 0.011). The mean ON duration time increased by 56 minutes at week 6 (p = 0.041) and 38 minutes at week 12 (p = 0.035). The total UPDRS scores (p<0.0001), scores for parts II (p = 0.001), III (p<0.0001) and IV (p = 0.009) were significantly better. The total PDQ-39 scores (p = 0.001) and subdomains mobility (p = 0.002), ADL (p = 0.001), emotional well being (p = 0.026) and stigma (p = 0.034) significantly improved. The PD NMSQ did not show significant improvement.

Conclusions

H. pylori eradication improved levodopa onset time, ON duration, motor severity and quality of life parameters. Screening and eradication of H. pylori is inexpensive and should be recommended in PD patients, particularly those with erratic response to levodopa.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02112812","term_id":"NCT02112812"}}NCT02112812     

Cranialization of the Frontal Sinus for Secondary Mucocele Prevention following Open Surgery for Benign Frontal Lesions

Objective

To compare frontal sinus cranialization to obliteration for future prevention of secondary mucocele formation following open surgery for benign lesions of the frontal sinus.

Study Design

Retrospective case series.

Setting

Tertiary academic medical center.

Patients

Sixty-nine patients operated for benign frontal sinus pathology between 1994 and 2011.

Interventions

Open excision of benign frontal sinus pathology followed by either frontal obliteration (n = 41, 59%) or frontal cranialization (n = 28, 41%).

Main Outcome Measures

The prevalence of post-surgical complications and secondary mucocele formation were compiled.

Results

Pathologies included osteoma (n = 34, 49%), mucocele (n = 27, 39%), fibrous dysplasia (n = 6, 9%), and encephalocele (n = 2, 3%). Complications included skin infections (n = 6), postoperative cutaneous fistula (n = 1), telecanthus (n = 4), diplopia (n = 3), nasal deformity (n = 2) and epiphora (n = 1). None of the patients suffered from postoperative CSF leak, meningitis or pneumocephalus. Six patients, all of whom had previously undergone frontal sinus obliteration, required revision surgery due to secondary mucocele formation. Statistical analysis using non-inferiority test reveal that cranialization of the frontal sinus is non-inferior to obliteration for preventing secondary mucocele formation (P<0.0001).

Conclusion

Cranialization of the frontal sinus appears to be a good option for prevention of secondary mucocele development after open excision of benign frontal sinus lesions.     

Is IP-10 a Better Biomarker for Active and Latent Tuberculosis in Children than IFNγ?

Background

The blood based interferon-gamma release assays (IGRA) for the diagnosis of tuberculosis do not discriminate between active TB disease and latent TB infection (LTBI). The search for distinguishing biomarkers therefore continues, as the accurate diagnosis of tuberculosis is particularly challenging in children. IFN-γ-inducible protein 10 (IP-10/CXCL10) has recently been evaluated as a marker for active TB in adults with promising results.

Aim

To investigate this new biomarker for active TB and LTBI in paediatrics.

Method

We measured IP-10 levels using ELISA in supernatants of whole blood samples stimulated with TB-specific-antigens and negative control antigen.

Results

IP-10 is produced in high levels following mycobacterial antigen stimulation in active TB (n = 17) and LTBI (n = 16) compared to controls (n = 16) and to IFN-γ. The baseline levels of IP-10 are increased in active TB and in LTBI, but there is no significant difference of stimulated levels of IP-10 between active TB and LTBI.

Conclusions

IP-10 is a biomarker for tuberculosis in children. However like IFNγ, IP-10 also does not distinguish between active TB and LTBI.     

Downregulation of 14-3-3σ Correlates with Multistage Carcinogenesis and Poor Prognosis of Esophageal Squamous Cell Carcinoma

Aims

The asymptomatic nature of early-stage esophageal squamous cell carcinoma (ESCC) results in late presentation and consequent dismal prognosis This study characterized 14-3-3σ protein expression in the multi-stage development of ESCC and determined its correlation with clinical features and prognosis.

Materials and Methods

Western blot was used to examine 14-3-3σ protein expression in normal esophageal epithelium (NEE), low grade intraepithelial neoplasia (LGIN), high grade intraepithelial neoplasia (HGIN), ESCC of TNM I to IV stage and various esophageal epithelial cell lines with different biological behavior. Immunohistochemistry was used to estimate 14-3-3σ protein in 110 biopsy samples of NEE, LGIN or HGIN and in 168 ESCC samples all of whom had follow-up data. Support vector machine (SVM) was used to develop a classifier for prognosis.

Results

14-3-3σ decreased progressively from NEE to LGIN, to HGIN, and to ESCC. Chemoresistant sub-lines of EC9706/PTX and EC9706/CDDP showed high expression of 14-3-3σ protein compared with non-chemoresistant ESCC cell lines and immortalized NEC. Furthermore, the downregulation of 14-3-3σ correlated significantly with histological grade (P = 0.000) and worse prognosis (P = 0.004). Multivariate Cox regression analysis indicated that 14-3-3σ protein (P = 0.016) and T stage (P = 0.000) were independent prognostic factors for ESCC. The SVM ESCC classifier comprising sex, age, T stage, histological grade, lymph node metastasis, clinical stage and 14-3-3σ, distinguished significantly lower- and higher-risk ESCC patients (91.67% vs. 3.62%, P = 0.000).

Conclusions

Downregulation of 14-3-3σ arises early in the development of ESCC and predicts poor survival, suggesting that 14-3-3σ may be a biomarker for early detection of high-risk subjects and diagnosis of ESCC. Our seven-feature SVM classifier for ESCC prognosis may help to inform clinical decisions and tailor individual therapy.     

Quantitative Analysis of Coronary Vessels with Optimized Intracoronary CT Number

Background

Variability in intracoronary computed tomography (CT) number may influence vessel quantification. We confirmed the feasibility of a novel method for measuring vessel diameter and area using coronary CT angiography (CCTA) with an optimized intracoronary CT number, 350 HU.

Methods

We performed intravascular ultrasound (IVUS) imaging in 52 patients with significant stenosis detected by coronary CT angiography targeting 350 HU using a CT number-controlling system. We measured 0-to-0 HU distances in the cross-sectional coronary images of 32 patients. We analyzed the ratio of 0-to-0 HU distances in CT images to media-to-media distances in IVUS images (C:I ratio). The area of ≥0 HU for 103 representative points in the remaining 20 patients was compared to the area of the traced external elastic membrane (EEM) in IVUS images.

Results

There was a strong correlation between 0-to-0 HU distance in CT images and media-to-media diameter in IVUS images (r = 0.97, p<0.001). The C:I ratio was 1.1. EEM area was estimated by dividing the area of ≥0 HU by the square of C:I. There was also a strong correlation between the estimated EEM area and the EEM area in IVUS images (r = 0.95, p<0.001).

Conclusions

Media-to-media diameter and EEM area can be estimated by CCTA targeting the optimized intracoronary CT number when blood vessel borders are defined at 0 HU.     

IOL Tilt and Decentration Estimation from 3 Dimensional Reconstruction of OCT Image

Purpose

To evaluate intraocular lens (IOL) tilt and decentration by anterior segment optical coherence tomography (AS-OCT) using 3-dimensional (3D) reconstruction method.

Design

Prospective observational case series.

Participants

Thirty-nine patients (39 eyes) were included.

Methods

The IOL positions of all eyes were examined by AS-OCT. Images were obtained in 4 axes (0–180 degrees, 45–225 degrees, 90–270 degrees, and 135–315 degrees) using the quadrant-scan model. The cross-sectional images were analyzed with MATLAB software.

Main Outcome Measures

The angle (θ) between the reference pupillary plane and the IOL plane, the distances between the center points of the pupil circle and the IOL on the x-axis (dx) and y-axis (dy) and the spatial distance (ds) were calculated after 3D-reconstruction.

Results

The mean angle (θ) between the pupillary plane and the IOL plane was 2.94±0.99 degrees. The mean IOL decentration of dx and dy was 0.32±0.26 mm and 0.40±0.27 mm, respectively. The ds of the IOL decentration was 0.56±0.31 mm. There was no significant correlation between the ocular residual astigmatism (ORA) and the tilted angle or the decentration distance. There was a significant correlation between the ORA and total astigmatism (r = 0.742, P<0.001). There was no significant correlation between the postoperative best corrected visual acuity (BCVA) and the ORA (r = 0.156; P = 0.344), total astigmatism (r = 0.012; P = 0.942), tilted angle (θ; r = 0.172; P = 0.295) or decentration distance (dx: r = 0.191, P = 0.244; dy: r = 0.253, P = 0.121; ds: r = 0.298, P = 0.065).

Conclusions

AS-OCT can be used as an alternative for the analysis of IOL tilt and decentration using 3D-reconstruction.     

Subthalamic Nucleus Deep Brain Stimulation Does Not Improve Visuo-Motor Impairment in Parkinson’s Disease

Objective

To evaluate how bilateral subthalamic nucleus deep brain stimulation (STN-DBS) affects visuo-motor coordination (VMC) in patients with Parkinson’s disease (PD).

Background

VMC involves multi-sensory integration, motor planning, executive function and attention. VMC deficits are well-described in PD. STN-DBS conveys marked motor benefit in PD, but pyscho-cognitive complications are recognized and the effect on VMC is not known.

Methods

Thirteen PD patients with bilateral STN-DBS underwent neurological, cognitive, and mood assessment before VMC testing with optimal DBS stimulation parameters (‘on-stimulation’) and then, on the same day without any medication changes, after DBS silencing and establishing motor function deterioration (‘off-stimulation’). Twelve age-matched healthy controls performed 2 successive VMC testing sessions, with a break of similar duration to that of the PD group. The computer cursor was controlled with a dome-shaped ‘mouse’ hidden from view that minimized tremor effects. Movement duration, hand velocity, tracking continuity, directional control variables, and feedback utilization variables were measured. MANOVA was performed on (1) clinically measured motor function, (2) VMC performance and (3) mood and attention, looking for main and interaction effects of: (1) group (controls/PD), (2) test-order (controls: first/second, PD: on-stimulation/off-stimulation), (3) path (sine/square/circle) and (4) hand (dominant/non-dominant).

Results

Unified PD Rating Scale (UPDRS) Part III worsened off-stimulation versus on-stimulation (mean: 42.3 versus 21.6, p = 0.02), as did finger tapping (p = 0.02), posture-gait (p = 0.01), upper limb function (p<0.001) and backwards digit span (p = 0.02). Stimulation state did not affect mood. PD patients performed worse in non-velocity related VMC variables than controls (F_(5,18) = 8.5, p<0.001). In the control group there were significant main effects of hand (dominant/non-dominant), path (sine/square/circle) and test-order (Test_1/Test_2). In the PD group, hand and path effects, but no test-order (on-stimulation/off-stimulation), were found.

Conclusions

‘Low-level’ clinically-measured motor function responds to STN-DBS but ‘high-level’ motor and cognitive functions relating to VMC may be unresponsive to STN-DBS.