Comparison of electroretinographic measurements between tabletop and handheld stimulators in healthy subjects.

PURPOSE: To compare full-field electroretinography (ffERG) parameters obtained from handheld and tabletop electroretinography (ERG) devices in normal subjects. METHODS: Twenty volunteers underwent ffERG using a tabletop and handheld stimulator. The responses obtained from the right eyes were compared. The coefficient of variation and intraclass correlation coefficient (ICC) were derived to assess inter- and intra-individual reliability. RESULTS: The b-wave in the rod response, a- and b-waves in the maximal combined response, a-wave in the cone response, and the 30-Hz flicker response showed significantly greater amplitudes when recorded with the tabletop stimulator than with the handheld stimulator. The implicit time of response (ITR) in the 30-Hz flicker response was longer when recorded with the handheld stimulator than when recorded with the tabletop stimulator. With regard to amplitude, the ICC indicated moderate-to-high reliability in the measurement of the b-wave in the rod response, and a- and b-waves in the maximal combined response. With regard to ITR, measurement of the b-wave in the rod response and a-wave in the maximal combined response showed moderate-to-high reliability. CONCLUSION: Despite the significantly lower ERG amplitude measurements recorded by the handheld stimulator, there were no significant differences in variability between the two stimulators.

The mechanism of attenuation of epithelial-mesenchymal transition by a phosphodiesterase 5 inhibitor via renal klotho expression.

Phosphodiesterase-5 (PDE-5) inhibitors induces vasodilation in several organs by blocking cyclic GMP (guanosine monophosphate) degradation. However, the existence of alternative mechanism of action in case of an impaired nitric oxide (NO) system remains controversial. Previous studies suggested that decreased NO bioavailability may result in the downregulation of klotho expression, but the relationship between klotho and NO remains obscure. Therefore, we investigated whether a PDE-5 inhibitor could preserve epithelial-mesenchymal transition (EMT) and relationship exists between the NO and renal klotho expression. Ten-week-old SD rats (N = 24, 200 g, male) were divided (N = 6) into four groups, which received: A LSD, L-NAME 1 mg/mL in drinking water, Udenafil 5 mg/kg subcutaneously and both for 4 weeks. Urine nitrate/nitrite, NGAL (Neutrophil gelatinase-associated lipocalin), and cGMP were measured using ELISA. Kidney was subjected to evaluate PCNA (proliferative cell nuclear antigen), α-SMA (smooth muscle cell antigen), E-cadherin, and klotho expression. Urine cGMP decreased after treatment of PDE-5 inhibitor compared with control due to blocking degradation of cGMP (P < .05, control vs Udenafil and L-NAME with Udenafil groups). Urine NGAL increased after treating of L-NAME and attenuated after using PDE-5 inhibitor (P < .05, control vs L-NAME and L-NAME with Udenafil). PCNA, α-SMA, and E-cadherin (EMT markers) increased after L-NAME treatment and normalized after using PDE-5 inhibitor. Klotho expression showed trend to increase in the L-NAME with PDE-5 inhibitor group compared with the L-NAME group, however, eNOS expression did not change after treatment of L-NAME or PDE-5 inhibitor compared with control. PDE-5 inhibitor alleviates EMT in the kidney via klotho modulation independent of the NO system.

Is Dominant-Side Onset Associated With a Better Motor Compensation in Parkinson's Disease?

INTRODUCTION: Unilateral onset and persistent asymmetry of motor signs are unique features of PD. The dominant hemisphere may have more efficient motor networks with greater neural reserve to cope with pathological changes. Therefore, this study compared dominant-side onset and non-dominant-side onset PD to evaluate whether dominant-side onset patients have greater neural reserve and fewer motor deficits despite similar pathological changes. METHODS: We included the data of 157 consecutive, de novo PD patients with documented right-handedness who underwent dopamine transporter PET scans for an initial diagnostic workup. Among them, 118 patients with significant asymmetric motor deficits were selected for the analyses. RESULTS: Dominant-side patients (i.e., the majority of motor deficits on the right side) showed significantly fewer motor deficits (i.e., the part III score of the UPDRS) than non-dominant-side patients (18.0 ± 8.1 and 22.9 ± 10.1, respectively; P = 0.005). Other variables, including symptom duration and striatal dopaminergic activities, were similar between the two groups. A general linear model showed that this difference in motor deficits remained statistically significant after controlling for patient age, sex, symptom duration, and striatal dopaminergic activity in the posterior putamen (P = 0.013). CONCLUSION: These results suggest that dominant-side patients have greater neural reserve, allowing them to better cope with PD-related pathological changes (i.e., fewer motor deficits despite similar dopamine reduction) compared to non-dominant-side patients.

Clinical and radiological outcomes with an augmented baseplate for superior glenoid wear in reverse shoulder arthroplasty.

Aims: This study aimed to assess the impact of using the metal-augmented glenoid baseplate (AGB) on improving clinical and radiological outcomes, as well as reducing complications, in patients with superior glenoid wear undergoing reverse shoulder arthroplasty (RSA). Methods: From January 2016 to June 2021, out of 235 patients who underwent primary RSA, 24 received a superior-AGB after off-axis reaming (Group A). Subsequently, we conducted propensity score matching in a 1:3 ratio, considering sex, age, follow-up duration, and glenoid wear (superior-inclination and retroversion), and selected 72 well-balanced matched patients who received a standard glenoid baseplate (STB) after eccentric reaming (Group B). Superior-inclination, retroversion, and lateral humeral offset (LHO) were measured to assess preoperative glenoid wear and postoperative correction, as well as to identify any complications. Clinical outcomes were measured at each outpatient visit before and after surgery. Results: There were no significant differences in demographic data and preoperative characteristics between the two groups. Both groups showed significant improvements in patient-reported outcome measures (visual analogue scale for pain, visual analogue scale for function, American Shoulder and Elbow Surgeons, Constant, and Simple Shoulder Test scores) from preoperative to final assessment (p < 0.001). However, AGB showed no additional benefit. Notably, within range of motion, Group B showed significant postoperative decrease in both external rotation and internal rotation, unlike Group A (p = 0.028 and 0.003, respectively). Both groups demonstrated a significant correction of superior-inclination after surgery, while patients in Group B exhibited a significant decrease in LHO postoperatively (p = 0.001). Regarding complications, Group A experienced more acromial stress fractures (3 cases; 12.5%), whereas Group B had a higher occurrence of scapular notching (24 cases; 33.3%) (p = 0.008). Conclusion: Both eccentric reaming with STB and off-axis reaming with AGB are effective methods for addressing superior glenoid wear in RSA, leading to improved clinical outcomes. However, it is important to be aware of the potential risks associated with eccentric reaming, which include excessive bone loss leading to reduced rotation and scapular notching.

In silico modeling to predict drug-induced phospholipidosis.

Drug-induced phospholipidosis (DIPL) is a preclinical finding during pharmaceutical drug development that has implications on the course of drug development and regulatory safety review. A principal characteristic of drugs inducing DIPL is known to be a cationic amphiphilic structure. This provides evidence for a structure-based explanation and opportunity to analyze properties and structures of drugs with the histopathologic findings for DIPL. In previous work from the FDA, in silico quantitative structure-activity relationship (QSAR) modeling using machine learning approaches has shown promise with a large dataset of drugs but included unconfirmed data as well. In this study, we report the construction and validation of a battery of complementary in silico QSAR models using the FDA's updated database on phospholipidosis, new algorithms and predictive technologies, and in particular, we address high performance with a high-confidence dataset. The results of our modeling for DIPL include rigorous external validation tests showing 80-81% concordance. Furthermore, the predictive performance characteristics include models with high sensitivity and specificity, in most cases above ≥80% leading to desired high negative and positive predictivity. These models are intended to be utilized for regulatory toxicology applied science needs in screening new drugs for DIPL.

Effect of using a small baseplate on the radiological and clinical outcomes of reverse total shoulder arthroplasty in Asian patients.

Aims: The aim of this study was to compare the clinical and radiological outcomes of reverse shoulder arthroplasty (RSA) using small and standard baseplates in Asian patients, and to investigate the impact of a mismatch in the sizes of the glenoid and the baseplate on the outcomes. Methods: This was retrospective analysis of 50 and 33 RSAs using a standard (33.8 mm, ST group) and a small (29.5 mm, SM group) baseplate of the Equinoxe reverse shoulder system, which were undertaken between January 2017 and March 2021. Radiological evaluations included the size of the glenoid, the ß-angle, the inclination of the glenoid component, inferior overhang, scapular notching, the location of the central cage in the baseplate within the vault and the mismatch in size between the glenoid and baseplate. Clinical evaluations included the range of motion (ROM) and functional scores. In subgroup analysis, comparisons were performed between those in whom the vault of the glenoid was perforated (VP group) and those in whom it was not perforated (VNP group). Results: Perforation of the vault of the glenoid (p = 0.018) and size mismatch in height (p < 0.001) and width (p = 0.013) were significantly more frequent in the ST group than in the SM group. There was no significant difference in the clinical scores and ROM in the two groups, two years postoperatively (all p > 0.05). In subgroup analysis, the VP group had significantly less inferior overhang (p = 0.009), more scapular notching (p = 0.018), and more size mismatch in height (p < 0.001) and width (p = 0.025) than the VNP group. Conclusion: In Asian patients with a small glenoid, using a 29.5 mm small baseplate at the time of RSA was more effective in reducing size mismatch between the glenoid and the baseplate, decreasing the incidence of perforation of the glenoid vault, and achieving optimal positioning of the baseplate compared with the use of a 33.8 mm standard baseplate. However, longer follow-up is required to assess the impact of these findings on the clinical outcomes.

Scanning laser ophthalmoscope imaging stabilized microperimetry in dry age-related macular degeneration.

PURPOSE: To determine the effect of drusen and geographic atrophy (GA) in dry age-related macular degeneration on retinal sensitivity using an eye tracking scanning laser ophthalmoscope microperimetry. METHODS: A total of 44 eyes from 22 patients with dry age-related macular degeneration and drusen and 11 patients with GA were imaged with scanning laser ophthalmoscope microperimetry (OPKO Health, Miami, FL). A custom microperimetry pattern was used to evaluate retinal sensitivity to a Goldmann III size target (108 µm on the retina). The perimetry used a 4-2 stepladder algorithm to determine maximal sensitivity. Microperimetry and optical coherence tomography were performed using a standardized protocol. Twenty-eight eyes with drusen and 16 eyes with GA were analyzed. RESULTS: Retinal sensitivity overlying drusen was significantly reduced compared with the adjacent uninvolved retina. There was a significant correlation between retinal sensitivity and drusen volume, as well as the grading of the photoreceptor inner segment/outer segment junction score. In patients with GA, an absolute scotoma was confirmed. Retinal sensitivity at the margin of GA was significantly decreased compared with the adjacent uninvolved retina. CONCLUSION: Scanning laser ophthalmoscope microperimetry is able to detect changes in retinal sensitivity in AMD patients overlying drusen and at the margin of GA. It is a useful device to grade focal retinal sensitivity in patients with dry age-related macular degeneration.

The effect of hypercholesterolemia on rotator cuff disease.

BACKGROUND: The causes of rotator cuff tendon rupture are multifactorial and still unclear. Intrinsic and extrinsic factors have been implicated as predisposing risk factors for rotator cuff rupture. Previous studies have suggested a relationship between elevated serum lipid profiles and tendon ruptures, although not rotator cuff tears specifically. QUESTIONS/PURPOSES: We therefore asked whether patients with rotator cuff tears were more likely to have higher levels of hypercholesterolemia than patients with shoulder pain but without tears. METHODS: We prospectively collected serum cholesterol and lipid profiles on two age-matched populations of patients; 74 (mean age, 66.3 years) had ruptures of their rotator cuff tendons, whereas a control group of 73 patients (mean age, 67.4 years) were seen for nontendon-related shoulder complaints. RESULTS: Total cholesterol, triglycerides, and low-density lipoprotein cholesterol concentrations of the patients with rotator cuff tendon tears were higher, and their high-density lipoprotein cholesterol showed a trend to being lower than the control group. Forty-seven of 74 patients (63%) with rotator cuff tears had an elevated serum cholesterol (total cholesterol greater than 240 mg/dL) as compared with an overall rate of 28% in our control group. CONCLUSIONS: Patients with rotator cuff tears were more likely to have hypercholesterolemia when compared with the control group. CLINICAL RELEVANCE: Measurement of serum cholesterol in patients presenting with torn rotator cuff tendons should be considered in patients whose cholesterol profiles are unknown. Future consideration of drug treatment may reduce risk for future tendon degeneration, as well as improve quality of life and reduce mortality. LEVEL OF EVIDENCE: Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Functional brain imaging in pure akinesia with gait freezing: [18F] FDG PET and [18F] FP-CIT PET analyses.

Pure akinesia with gait freezing (PAGF) has characteristic features, including freezing of gait and prominent speech disturbance without rigidity or tremor. The purpose of this study was to investigate changes in brain glucose metabolism and presynaptic dopaminergic function in PAGF. By using [(18)F] fluorodeoxyglucose (FDG) PET, 11 patients with PAGF were compared with 14 patients with probable progressive supranuclear palsy (PSP), 13 patients with Parkinson's disease (PD), and 11 normal controls. [(18)F] N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane (FP-CIT) PET was performed in 11 patients with PAGF and with 10 normal controls. The PAGF patients showed decreased glucose metabolism in the midbrain when compared with normal controls. PSP patients showed a similar topographic distribution of glucose hypometabolism with additional areas, including the frontal cortex, when compared with normal controls. The FP-CIT PET findings in patients with PAGF revealed severely decreased uptake bilaterally in the basal ganglia. These findings suggest that both PAGF and PSP may be part of the same pathophysiologic spectrum of disease. However, the reason why PAGF manifests clinically in a different manner needs to be further elucidated.

Clinical role of 18F-FDG PET-CT in suspected and potentially operable cholangiocarcinoma: a prospective study compared with conventional imaging.

OBJECTIVES: This study was conducted to evaluate the clinical role of integrated positron emission and computed tomography (PET-CT) in patients with suspected and potentially operable cholangiocarcinoma. METHODS: Between October 2005 and May 2007, 123 patients with suspected cholangiocarcinoma were enrolled in this study after diagnostic workup, including biliary dynamic computed tomography (CT) and magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRI/MRCP) with magnetic resonance (MR) angiography. Patients with overt unresectable cholangiocarcinoma or gallbladder cancer diagnosed via conventional imaging were excluded. Consecutively, each enrolled patient underwent PET-CT. Data were prospectively collected and analyzed in comparison with CT and MRI/MRCP. RESULTS: The overall values for sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET-CT in primary tumor detection were 84.0%, 79.3%, 92.9%, 60.5%, and 82.9%, respectively. PET-CT demonstrated no statistically significant advantage over CT and MRI/MRCP in the diagnosis of primary tumor. According to different morphologic characteristics of cholangiocarcinoma, PET-CT showed no significant difference in detecting those of mass-forming, periductal-infiltrating, and intraductal-growing types. PET-CT revealed significantly higher accuracy over CT in the diagnosis of regional lymph nodes metastases (75.9%vs 60.9%, P= 0.004) and distant metastases (88.3%vs 78.7%, P= 0.004). Additional use of PET-CT for assessing resectability correctly showed different results from those determined by conventional imaging in 15 (15.9%) of 94 patients with cholangiocarcinoma. CONCLUSIONS: PET-CT improved the accuracy of preoperative staging in patients with cholangiocarcinoma planning to undergo curative resection. Thus, PET-CT had an important clinical impact on the selection of proper treatment.

Lymph node standardized uptake values at pre-treatment 18F-fluorodeoxyglucose positron emission tomography as a valuable prognostic factor for distant metastasis in nasopharyngeal carcinoma.

OBJECTIVE: The aim of the present study was to evaluate prognostic values of pre-treatment fluorine-18 fludeoxyglucose (18F-FDG) positron emission tomography (PET) parameters for predicting the distant metastasis (DM) of nasopharyngeal cancer. METHODS: 73 patients diagnosed with nasopharyngeal cancer with regional lymph node (LN) involvement, who underwent pre-treatment 18F-FDG PET evaluation between January 2005 and December 2012, were retrospectively reviewed. We assessed the 18F-FDG PET parameters of the primary tumours (T-) and regional LNs (N-). For patients with bilateral retropharyngeal, bilateral neck and/or supraclavicular LN involvement, we also assessed the 18F-FDG PET parameters of the farthest LN station [N(f)-]. The following 18F-FDG PET parameters were evaluated: maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), peak standardized uptake value (SUVpeak), metabolic tumour volumes (MTVs) (MTV30-MTV70, which were calculated as the tumour volume with 30%, 40%, 50%, 60% and 70% of the SUVmax as the threshold, respectively) and total lesion glycolysis (TLG) (TLG30-TLG70, which were determined by the product of each MTV and the corresponding SUVmean within that MTV). Distant metastasis-free survival (DMFS) rates were estimated from the date of the start of radiotherapy to the date of DM or last follow-up by the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify prognostic factors for DMFS. The median follow-up period was 53 months (range 12-110 months). RESULTS: Most patients (95%) received concurrent chemoradiotherapy. The major failure pattern was DM (15 of all patients, 21%) and the 5-year DMFS was 79%. In univariate analysis, the T-SUVmax, T-SUVmean, T-SUVpeak, N-SUVmax, N-SUVpeak, N(f)-SUVmax and N(f)-SUVpeak were significant prognostic factors for DMFS. In multivariate analysis, the T-SUVmax, T-SUVpeak, N(f)-SUVmax and N(f)-SUVpeak were significant prognostic factors for DMFS. Of these parameters, the N(f)-SUVmax (hazard ratio = 6.524; p = 0.001) and N(f)-SUVpeak (hazard ratio = 5.399; p = 0.001) were the strongest prognostic factors for DMFS. CONCLUSION: In patients with nasopharyngeal cancer with LN involvement, the standardized uptake value parameter of the farthest LN station seems to be an important 18F-FDG PET parameter for predicting DM. Further studies are needed to validate its clinical significance. Advances in knowledge: We found that pre-treatment 18F-FDG PET parameters of primary tumours and regional LNs (the SUVmax and SUVpeak of the primary tumour and the farthest LN station) were significant prognostic factors for DMFS in patients with nasopharyngeal carcinoma with LN involvement.

Premorbid exercise engagement and motor reserve in Parkinson's disease.

BACKGROUND: Life-long experiences of cognitive activity could enhance cognitive reserve, which may lead individuals to show less cognitive deficits in Alzheimer's disease, despite similar pathological changes. We performed this study to test whether premorbid physical activity may enhance motor reserve in Parkinson's disease (PD) (i.e., less motor deficits despite similar degrees of dopamine depletion). METHODS: We assessed engagement in premorbid leisure-time exercise among 102 drug naive PD patients who had been initially diagnosed at our hospital by dopamine transporter scanning. Patients were classified into tertile groups based on the frequency, duration, and intensity of the exercises in which they participated. RESULTS: Among patients with mild to moderate reductions in striatal dopaminergic activity (above the median dopaminergic activity), the exercise group of the highest tertile showed significantly lower motor scores (i.e., fewer motor deficits, 15.53 ± 6.25), despite similar degrees of dopamine reduction, compared to the combined group of the middle and the lowest tertiles (21.57 ± 8.34, p = 0.01). Nonetheless, the highest tertile group showed a more rapid decline in motor function related to reductions in striatal dopaminergic activity than the other two groups (p = 0.002 with the middle tertile group and p = 0.001 with the lowest tertile group). CONCLUSIONS: These results suggest that engagement in premorbid exercise acts as a proxy for an active reserve in the motor domain (i.e., motor reserve) in patients with PD.

Association of body mass index and the depletion of nigrostriatal dopamine in Parkinson's disease.

Several antecedent studies had reported close relationship between low body weight and Parkinson's disease (PD). However, there have been few investigations about the role of body weight to nigrostriatal dopaminergic neurodegeneration. This study enrolled 398 de novo patients with PD whom underwent [18F] N-(3-Fluoropropyl)-2ß-carbon ethoxy-3ß-(4-iodophenyl) nortropane positron emission tomography scan and body mass index (BMI) measurement. The relationships between BMI and dopamine transporter (DAT) activity were analyzed using linear regression analysis. A multivariate analysis adjusted for age, gender, disease duration, smoking status, coffee and tea consumption, and residence area revealed that BMI remained independently and significantly associated with DAT activity in all striatal subregions. Moreover, multiple logistic regression analyses showed that BMI was a significant predictor for the lowest quartile of DAT activity in the anterior putamen, ventral striatum, caudate nucleus, and total striatum. The present findings suggest that a low BMI might be closely associated with low density of nigrostriatal dopaminergic neurons in PD, which could support the evidence for the role of low body weight to PD-related pathologies.

Is normosmic Parkinson disease a unique clinical phenotype?

OBJECTIVE: Olfactory dysfunction is present in the majority of patients with early-stage Parkinson disease (PD) and can precede the onset of motor symptoms by many years. We performed this study to evaluate whether normosmic patients with PD had different clinical features compared to hyposmic patients. METHODS: We analyzed the data of 208 de novo patients with PD (mean age, 65.4 ± 9.7 years; range, 38-85 years; 104 men) who underwent both olfactory function tests and dopamine transporter (DAT) scans. RESULTS: Normosmic patients were significantly younger and had fewer motor deficits than hyposmic patients with PD. Striatal subregional DAT activities were comparable between the 2 groups, but intersubregional gradients were significantly higher in normosmic than hyposmic PD. A general linear model showed that normosmic patients with PD showed significantly fewer motor deficits after controlling the patient's age, sex, symptom duration, and DAT activity in the posterior putamen (p = 0.016). Levodopa-equivalent dose at approximately 2.5 years follow-up tended to be lower in normosmic than in hyposmic PD (p = 0.055). CONCLUSIONS: These results suggest that normosmic PD is a unique clinical phenotype with a more benign course, compared to hyposmic PD. Either less pathologic involvement in the olfactory system or a greater potential for olfactory neurogenesis in normosmic PD may contribute to this benign process compared to hyposmic PD.

Acromioclavicular joint pain in patients with adhesive capsulitis: a prospective outcome study.

Diagnosis of adhesive capsulitis is a clinical diagnosis based on history and physical examination. Afflicted patients exhibit active and passive loss of motion in all planes and a positive capsular stretch sign. The effect of adhesive capsulitis on acromioclavicular biomechanics leading to tenderness has not been documented in the literature. This study reports on the incidence of acromioclavicular tenderness in the presence of adhesive capsulitis. Furthermore, we note the natural history of such acromioclavicular joint pain in relation to that of adhesive capsulitis. Over a 2-year period (2005-2007), 84 patients undergoing initial evaluation for adhesive capsulitis were prospectively examined with the use of validated outcome measures and physical examination. Acromioclavicular joint tenderness results were compared and analyzed on initial evaluation and final follow-up of at least 1 year. Forty-eight patients (57%) with adhesive capsulitis had acromioclavicular joint pain on examination. At final follow-up, as range of motion improved, a significant increase in American Shoulder and Elbow Surgeons/Penn shoulder score and decrease in number of patients with acromioclavicular pain was noted with only 6 patients with residual pain (P<.05). In the presence of adhesive capsulitis, there is not only compensatory scapulothoracic motion but also acromioclavicular motion. This often results in transient symptoms at the acromioclavicular joint, which abate as the frozen shoulder resolves and glenohumeral motion improves. This is important to recognize to avoid unnecessary invasive treatment of the acromioclavicular joint when the patient presents with adhesive capsulitis.

Comparison of brain MRI and 18F-FDG PET in the differential diagnosis of multiple system atrophy from Parkinson's disease.

To investigate the diagnostic value of brain magnetic resonance image (MRI) and (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in the differentiation of multiple system atrophy (MSA) from Parkinson's disease (PD). Thirty-five patients with MSA (23 MSA-P and 12 MSA-C) and 17 patients with PD were included in this study. Overall correct diagnosis rates between clinical and imaging diagnosis among MSA-P, MSA-C, and PD patients were 80% for visual MRI analysis, 88.5% for visual (18)F-FDG PET analysis, and 84.3% for SPM-supported analysis of (18)F-FDG PET. The sensitivity of brain MRI, and visual and SPM analysis of (18)F-FDG PET in differentiating MSA from PD was 72.7%, 90.9%, and 95.5%, respectively, the specificity was 100% for each imaging analysis, the positive predictive value was 100% for each imaging analysis, and the negative predictive value was 60%, 81.8%, and 90%, respectively. Our results suggest that brain MRI and (18)F-FDG PET are diagnostically useful in differentiating MSA (MSA-P and MSA-C) from PD, and indicate that (18)F-FDG PET has a tendency toward higher sensitivity compared to brain MRI, but a larger longitudinal study including pathological data will be required to confirm our findings.

Clinical outcomes of chronic hepatitis B patients with persistently detectable serum hepatitis B virus DNA during lamivudine therapy.

BACKGROUND AND AIM: A small proportion of chronic hepatitis B patients have persistently detectable serum hepatitis B virus (HBV) DNA despite lamivudine therapy. The incidence and clinical outcomes of patients who persistently have detectable serum HBV-DNA during lamivudine therapy was investigated. METHOD: We enrolled 221 chronic hepatitis B patients who underwent lamivudine therapy for more than 6 months. Among them, 180 were HBeAg positive. Serum HBV-DNA, HBeAg, anti-HBe and alanine aminotransferase (ALT) levels were serially monitored. The study groups were defined, using a hybridization assay, as patients with reductions in serum HBV-DNA below the detectable level (group I) or patients with persistently detectable serum HBV-DNA (group II) during the initial 6 months of lamivudine therapy. RESULTS: The incidence of patients who had persistently detectable HBV-DNA was 7.7%. After the first year, the rates of viral breakthrough, HBeAg loss and serum ALT normalization of group I versus group II were 21% versus 63%, 38% versus 0%, and 71% versus 28%, respectively (P < 0.001). The log(10) reduction of serum HBV-DNA at 6 months was -4.58 log(10) for group I and -1.97 log(10) for group II (P < 0.001, bDNA assay). There were no pretreatment lamivudine-resistant mutants in group II. CONCLUSION: Lamivudine had little effect on serum HBV-DNA suppression, viral breakthrough suppression and rate of HBeAg loss and ALT normalization in chronic hepatitis B patients with persistently detectable serum HBV-DNA during the initial 6 months of therapy. Early termination of lamivudine therapy is advocated for these patients.