Search

Aims/Introduction Clinical studies show that either heart rate variability (HRV) or electrochemical skin conductance (ESC) alone can serve as a simple and objective method for screening cardiovascular autonomic neuropathy (CAN). We tested the hypothesis that combining these two quantitative approaches can not only reinforce accuracy in CAN screening but also provide a better estimate of CAN severity in patients with type 2 diabetes (T2DM) who had already had CAN in outpatient clinics. Materials and Methods Each patient received a complete battery of cardiovascular autonomic reflex tests (CARTs), with ESC measured by SUDOSCAN, time domain of HRV measured by standard deviation of all normal RR intervals (SDNN) and frequency domain of HRV (low frequency [LF], high frequency [HF], and LF/HF ratio), and peripheral blood studies for vascular risk factors. Severity of CAN was measured by CAN score. Results The 90 T2DM patients included 50 males and 40 females. Those with more severe CAN had lower values in feet ESC (P = 0.023) and SDNN (P

Background. Myasthenia gravis (MG) is an immune-mediated disorder characterized by muscle fatigue and fluctuating weakness. Impairment in respiratory strength and endurance has been described in patients with generalized MG. We tested the hypothesis that respiratory muscle training (RMT) can improve functional outcomes and reduce fatigue in patients with MG. Methods. Eighteen patients with mild to moderate MG participated in this study. The training group underwent home-based RMT three times a week for 12 weeks. Sixteen patients with MG without RMT were enrolled as a disease control group. Lung function, autonomic testing, Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF), and functional outcome measurement by using quantitative myasthenia gravis (QMG) score and myasthenia gravis composite (MGC) scale were measured before and after the 12-week RMT. Results. The 12-week RMT significantly increased forced vital capacity (FVC) from 77.9±12.6% to 83.8±17.7% (p=0.03), forced expiratory volume in one second (FEV1) from 75.2±18.3% to 83.3±19.0% (p=0.002), and 6-minute walking distance from 403.4±72.2 m to 466.1±68.5 m (p=0.003). The QMG score improved from 9.6±4.1 to 8.1±4.3 (p=0.04) and the MGC scale from 4.4±3.5 to 2.7±2.9 (p=0.02). The fatigue score (MFSI-SF) reduced from 17.1±14.7 to 13.5±16.9 (p=0.03). Conclusion. The home-based RMT is an effective pulmonary function training for MG patients. The RMT can not only improve short-term outcomes but also reduce fatigue in patients with mild to moderate generalized MG.

Studies showed a relatively prolonged blink R1 latency in patients with diabetic distal symmetrical polyneuropathy (DSPN) compared to that without DSPN. We tested the hypothesis that blink R1 latency would provide a diagnostic alternative to nerve conduction studies (NCS) in DSPN and act as a marker of the severity of NCS abnormalities in DSPN.A total of 109 patients with type 2 diabetes underwent blink reflex studies and NCS. We used the composite amplitude scores of nerve conductions (CAS), which consisted of motor (tibial, peroneal and ulnar) and sensory (sural and ulnar) amplitudes for estimating the severity of NCS.Patients with DSPN had longer blink R1, R2, and contralateral R2 latencies (P 0.0001, P = 0.001, and P = 0.031, respectively) and higher CAS (P 0.0001). Area under curve on receiver operating characteristic curve analysis in diagnosing occurrence of DSPN in blink R1 latency was 0.772 (P 0.0001). Multiple linear regression analysis showed that blink R1 latency was independently associated with CAS.Blink R1 latency may be valuable in auxiliary diagnosis and in determining the severity of NCS abnormalities in DSPN.Blink R1 latency can be added as a supplemental marker of severity of NCS in DSPN, especially if the patient's sural amplitudes has a floor effect.

INTRODUCTION The sural sensory nerve action potential (SNAP) amplitude is a measure of the number of axons. We tested the hypothesis that sural SNAP amplitude can be used as a marker in screening, severity evaluation, and follow-up of diabetic distal symmetrical polyneuropathy (DSPN). METHODS Patients with type 2 diabetes underwent nerve conduction studies and were followed for 6 years. Composite amplitude scores (CASs) were determined to evaluate DSPN severity. RESULTS Sural SNAP amplitudes were negatively correlated with CAS (r = -.790, P

Atrial fibrillation (AF)-related stroke causes severe disability and poor prognosis. Adjunctive statin therapy has been recommended for atherosclerotic-related stroke but not AF-related stroke. This study investigated the effects of statin in AF patients who experienced acute ischemic stroke.Data from patients with AF experiencing first-ever ischemic stroke between 2001 and 2010 were collected from the Taiwan National Health Insurance Research Database and categorized into non-statin and statin groups. The statin group was further divided into pre-stroke statin (those who began statin therapy before stroke) and post-stroke statin (those who began statin therapy after stroke) groups. The risks for recurrent ischemic stroke, coronary artery disease (CAD), intracranial hemorrhage (ICH), and 1-year mortality were compared among the groups.A total of 43,242 patients were in the non-statin, 2858 in the pre-stroke statin and 4640 in post-stroke statin groups. Comparing the risk for recurrent stroke and CAD among the three groups, the pre-stroke statin and post-stroke statin groups did not exhibit a significant difference compared with the non-statin group. In terms of ICH risk, the statin group had a lower risk for ICH (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.68-0.90; p = 0.0007) compared with the non-statin group. The overall 1-year mortality in both statin subgroups was lower than that in the non-statin group (pre-stroke statin, OR 0.55 [95% CI 0.49-0.61]; p 0.0001 versus post-stroke statin, OR 0.53 [95% CI 0.48-0.58]; p 0.0001).Statin therapy reduced the risk of ICH and 1-year mortality in AF patients who experienced acute ischemic stroke.

Decompressive craniectomy (DC) has been performed increasingly to control medically refractory intracranial hypertension in patients with traumatic brain injury (TBI). Although DC is a potentially life-saving procedure and technically straightforward, it is associated with some significant complications that include subdural hygroma (SDG) and posttraumatic hydrocephalus (PTH). A retrospective analysis of 143 TBI patients who underwent unilateral DC was undertaken to investigate the incidence and risk factors of PTH and investigate the relationship between the types of SDG and PTH. Among these patients, the incidence of PTH was 30.1%. SDG was noted in 25 patients (58.1%) who developed PTH. SDG was noted in 27 patients (27%) without PTH. The patients with PTH had a significantly unfavorable outcome (p < 0.0001). After stepwise logistic regression analyses, only age (p = 0.004, odds ratio [OR] = 1.036, 95% confidence interval [CI] = 1.011-1.061) and contralateral SDG (p < 0.0001, OR = 5.613, 95% CI = 2.232-14.115) remained independently associated with PTH development, and PTH development rate increased by 3.6% with every 1-year increase in age. Close surveillance is indicated in older TBI patients with contralateral SDG after unilateral DC to prompt early detection and timely management of PTH.

Background Cerebellar hemorrhage is a potentially life-threatening condition and neurologic deterioration during hospitalization could lead to severe disability and poor outcome. Finds out the factors influencing neurologic deterioration during hospitalization is essential for clinical decision-making. Methods One hundred fifty-five consecutive patients who suffered a first spontaneous cerebellar hemorrhage (SCH) were evaluated in this 10-year retrospective study. This study aimed to identify potential clinical, radiological and clinical scales risk factors for neurologic deterioration during hospitalization and outcome at discharge. Results Neurologic deterioration during hospitalization developed in 17.4% (27/155) of the patient cohort. Obliteration of basal cistern (p≦0.001) and hydrocephalus (p≦0.001) on initial brain computed tomography (CT), median Glasgow Coma Scale (GCS) score at presentation (p≦0.001) and median intracerebral hemorrhage (ICH) score (P≦0.001) on admission were significant factors associated with neurologic deterioration. Stepwise logistic regression analysis showed that patients with obliteration of basal cistern on initial brain CT scan had an odds ratio (OR) of 9.17 (p = 0.002; 95% confidence interval (CI): 0.026 to 0.455) adjusted risk of neurologic deterioration compared with those without obliteration of basal cistern. An increase of 1 point in the ICH score on admission would increase the neurologic deterioration rate by 83.2% (p = 0.010; 95% CI: 1.153 to 2.912). The ROC curves showed that the AUC for ICH score on presentation was 0.719 (p = 0.000; 95% CI: 0.613–0.826) and the cutoff value was 2.5 (sensitivity 80.5% and specificity 73.7%). Conclusion Patients had obliteration of basal cistern on initial brain CT and ICH score greater or equal to 3 at admission implies a greater danger of neurologic deterioration during hospitalization. Cautious clinical assessments and repeated brain images study are mandatory for those high-risk patients to prevent neurologic deterioration during hospitalization.

Background The elderly, and especially those with an immuno-compromised status, are vulnerable to infectious diseases. The purpose of this study was to examine the clinical characteristics and therapeutic outcomes of cryptococcal meningitis (CM) in elderly patients in Taiwan. Methods Ninety-nine adult patients with CM were identified during a 15-year study period (2002–2016), of whom 38 elderly (≥ 65 years) patients (16 men and 22 women, median age 72.9 years; range 65–86 years) were included for analysis. The clinical characteristics and therapeutic outcomes of these patients were analyzed and compared to non-elderly adult patients (

MINI: In this study, respiratory function at the time of extubation can be useful optimal clinical guidelines for weaning and extubation attempts in patients with acute cervical spinal cord injury. Serum thiobarbituric acid-reactive substances level at admission can be a useful predictor for severity in acute cervical patients with spinal cord injury.Patients who had suffered from acute blunt cervical spinal cord injury (SCI) and admitted our hospital within 24 hours after injury were included in the study.We compared the respiratory function and serum reactive oxidative stress (ROS) after acute cervical SCI, and tried to find out the valuable predictors of weaning in patients with acute cervical SCI.Ventilation impairment is a major complication of acute cervical SCI. Evidence of oxygen radical formation in secondary injury from animal SCI models demonstrates an immediate postinjury increase in ROS production after SCI. We hypothesize that the serum ROS is associated with the severity of patients with acute cervical SCI.Thirty-eight adult patients who had acute cervical SCI and 58 healthy volunteers were enrolled. Respiratory function at admission, at the time of extubation and at 48 hours after extubation, serum oxidative stress, Injury Severity Score and Japanese Orthopaedic Association score at admission were compared.The most notable predictor of mechanical ventilation more than 48 hours was serum thiobarbituric acid-reactive substances (TBARS) level at admission (P = 0.027), and the cut-off value of serum TBARS level was 731.7 μmol/L (sensitivity 87.5% and specificity 78.9%). For the reventilation ≤5 days, the notable predictors were respiratory function at the time of extubation (maximal inspiratory pressure, P = 0.040; maximal expiratory pressure, P = 0.020; and tidal volume, P = 0.036) and serum TBARS level at admission (P = 0.013), the cut-off value of serum TBARS level at admission was 762.3 μmol/L (sensitivity 100% and specificity 90.0%).In this study, respiratory function (maximal inspiratory pressure, maximal expiratory pressure, and tidal volume) at the time of extubation can be useful optimal clinical guidelines for weaning and extubation attempts in patients with acute cervical SCI. Serum TBARS level at admission can be a useful predictor for severity in acute cervical SCI patients.3.Patients who had suffered from acute blunt cervical spinal cord injury (SCI) and admitted our hospital within 24 hours after injury were included in the study. We compared the respiratory function and serum reactive oxidative stress (ROS) after acute cervical SCI, and tried to find out the valuable predictors of weaning in patients with acute cervical SCI. Ventilation impairment is a major complication of acute cervical SCI. Evidence of oxygen radical formation in secondary injury from animal SCI models demonstrates an immediate postinjury increase in ROS production after SCI. We hypothesize that the serum ROS is associated with the severity of patients with acute cervical SCI. Thirty-eight adult patients who had acute cervical SCI and 58 healthy volunteers were enrolled. Respiratory function at admission, at the time of extubation and at 48 hours after extubation, serum oxidative stress, Injury Severity Score and Japanese Orthopaedic Association score at admission were compared. The most notable predictor of mechanical ventilation more than 48 hours was serum thiobarbituric acid-reactive substances (TBARS) level at admission (P = 0.027), and the cut-off value of serum TBARS level was 731.7 μmol/L (sensitivity 87.5% and specificity 78.9%). For the reventilation ≤5 days, the notable predictors were respiratory function at the time of extubation (maximal inspiratory pressure, P = 0.040; maximal expiratory pressure, P = 0.020; and tidal volume, P = 0.036) and serum TBARS level at admission (P = 0.013), the cut-off value of serum TBARS level at admission was 762.3 μmol/L (sensitivity 100% and specificity 90.0%). In this study, respiratory function (maximal inspiratory pressure, maximal expiratory pressure, and tidal volume) at the time of extubation can be useful optimal clinical guidelines for weaning and extubation attempts in patients with acute cervical SCI. Serum TBARS level at admission can be a useful predictor for severity in acute cervical SCI patients. Level of Evidence: 3.

Background: Systemic inflammation with elevated oxidative stress causing neuroinflammation is considered a major factor in the pathogenesis of Parkinson’s disease (PD).The interface between systemic circulation and the brain parenchyma is the blood - brain barrier (BBB), which also plays a role in maintaining neurovascular homeostasis. Relatedly, intermediate vascular inflammation causing BBB dysfunction is a key component of PD pathogenesis. Vascular cell adhesion molecule-1 (VCAM-1) and microRNAs (miRNAs) regulate brain endothelial function, neoangiogenesis, and, in turn, neuronal homeostasis regulation, such that their dysregulation can result in neurodegeneration, such as gray matter atrophy, in PD. In this study, our aim was to evaluate the associations among specific levels of gray matter atrophy, peripheral vascular adhesion molecules, miRNAs, and clinical disease severity in order to achieve a clearer understanding of PD pathogenesis.Methods: Blood samples were collected from 33 patients with PD and 27 healthy volunteers, and the levels of VCAM-1 and several miRNAs in those samples were measured. Voxel-based morphometry (VBM) analysis was performed using 3T magnetic resonance imaging (MRI) and SPM (Statistical Parametric Mapping software program). The associations among the vascular parameter, miRNAs, gray matter volume and clinical disease severity measurements were evaluated by partial correlation analysis.Results: The levels of VCAM-1, miRNA-22 and miRNA-29a expression were significantly elevated in the PD patients. The gray matter volume atrophy in the left parahippocampus, bilateral posterior cingulate gyrus, fusiform gyrus, left temporal gyrus, and cerebellum was significantly correlated with increased clinical disease severity, the upregulation of miRNA levels, and increased vascular inflammation.Conclusions: Patients with PD seem to have abnormal levels of vascular inflammatory markers and miRNAs in the peripheral circulation, and these levels are correlated with specific brain volume changes. This study reinforces the associations among peripheral inflammation, the BBB interface, and gray matter atrophy in PD, and further demonstrates that BBB dysfunction with neurovascular impairment may play an important role in PD progression.

Background. Several comorbidities contribute to an increased risk of infections in Parkinson’s disease (PD) as the disease progresses. However, few studies have examined the correlation between sepsis and PD. Aim. The aim of this study is to disclose the presentation and outcome of serious infection in patients with PD in the emergency department. Methods. This retrospective cohort study enrolled patients with PD who had serious infection and were admitted to the emergency department between January 2007 and December 2013. For clinical comparison, we compared the clinical features, laboratory data, and outcomes with those of age- and sex-matched patients who had serious infection but not PD. Results. There were a total of 1,200 episodes of infected PD patients and 2,400 age- and sex-matched infected patients without PD as disease controls. PD patients had fewer comorbidities and lower severity of infectious disease but longer hospital stays than control group patients. The incidences of respiratory tract and urinary tract infections were higher in PD patients. The levels of inflammatory and organ dysfunction biomarkers in PD were lower and compatible with the severity of infectious disease. A total of 86 (7.2%) infected PD patients died during the 28-day admission compared to 339 (14.1%) in non-PD patients. Serum C-reactive protein, bandemia, and lactate could be used to predict mortality in infected PD patients. Conclusions. In infected patients with PD, respiratory and urinary tract infections were the two most common infectious sources. Empiric therapy based on experience could treat both respiratory and urinary tract infections. Early diagnosis and treatment are essential for survival.

Background.Peritoneal dialysis (PD) is an increasingly popular therapeutic option for patients with advanced renal failure. However, intra-abdominal adhesions (IAA) represent a major unsolved problem in adequate PD performance. In this study, we investigated the role of previous abdominal surgery on the presence of subsequent IAA as well as outcomes in those patients with PD who had subsequent IAA.Methods.Two hundred and two patients who received continuous ambulatory peritoneal dialysis were prospectively enrolled in this study. We compared the PD adequacy indices and outcomes for technical failure in patients with and without subsequent IAA at presentation and a minimum of 2 years of follow-up.Results.Subsequent IAA accounted for 19% (38/202) of patients. Patients who had previous abdominal surgery had higher risks of subsequent IAA especially those patients who had higher mean ages (P=0.023). PD adequacy indices including both 24-hour dialysate volume and peritoneal WCcr L/week/1.73 m2were significantly lower in patients who had, as compared to those who did not have subsequent IAA (P=0.003 and 0.018, respectively). Although patients who had subsequent IAA had decreased PD adequacy, the development of technical failures during PD maintenance did not show significant differences at the 2-year minimum follow-up study.Conclusions.Subsequent IAA is not rare, especially in high-risk patients including those with previous abdominal surgery and higher mean ages. Although decreased PD adequacy after IAA was found, the development of technical failures was not significantly different at the 2-year minimum follow-up study.

The prognostic significance of clinical characteristics and neuroimaging features, especially cranial magnetic resonance imaging (MRI)-based neuroimaging features, in patients with human immunodeficiency virus (HIV)-negative cryptococcal meningitis (CM) has rarely been examined in the literature. We analyzed the clinical characteristics and MRI findings of 65 HIV-negative patients (43 men, 22 women, age 19–86 years) collected during a study period of 15 years (January 2001–December 2015). Their underlying conditions included diabetes mellitus, liver cirrhosis, hematologic disorders, autoimmune disorders, malignancy, chronic obstructive pulmonary disease, adrenal insufficiency and organ transplantation, and their clinical presentations included headache, altered consciousness, fever, seizure, visual disturbance and hearing impairment. The main cranial MRI findings were basal meningeal enhancement (44.6%, 29/65), dilated Virchow-Robin space/pseudocyst (43.1%, 28/65), “dirty” cerebrospinal fluid sign (38.5%, 25/65), hydrocephalus (36.9%, 21/65), acute/subacute cerebral infarct (ASCI, 21.5%, 14/65), cryptococcoma (9.2%, 6/65), and hazy brain base (1.5%, 1/65). The therapeutic results of the 65 patients were evaluated using the Glasgow Outcome Scale (GOS). A comparison of the good outcome group (GOS score = 4–5, n = 37) and poor outcome group (GOS score = 1–3, n = 28) revealed that both the presence of seizures and ASCI were significantly associated with the prognosis. A comparison of the groups with ASCI (n = 14) and without ASCI (n = 51) revealed that the presence of basal meningeal enhancement was a significant factor for the development of ASCI, and that this correlation may be associated with intense basal meningeal inflammation in adjacent small vessels.

Cardiovascular autonomic function impairment has been reported in patients with type 2 diabetes mellitus and is associated with cardiovascular events. In this study, we test the hypothesis that the severity of cardiovascular autonomic neuropathy is a predictor associated with subsequent 3-point major adverse cardiovascular events (3-P MACE; combined endpoint of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke).In this prospective study, we enrolled 168 patients with type 2 diabetes mellitus over a 6-year follow-up period. We constructed the Composite Autonomic Scoring Scale as a measure of the severity of cardiovascular autonomic neuropathy and examined baseline clinical and laboratory data of 168 patients with diabetes. Cardiovascular autonomic testing included heart rate response to deep breathing, Valsalva ratio and baroreflex sensitivity. Therapeutic outcome was defined as 3-P MACE.The overall incidence of new 3-P MACE was 23.2% and overall fatality rate was 9.5% during the 6-year follow-up period. Only underlying coronary heart disease and Composite Autonomic Scoring Scale were independently associated with subsequent 3-P MACE in the Cox proportional hazards model. Any increase of 1 point in Composite Autonomic Scoring Scale would increase the risk of new 3-P MACE by 9.7%. Area under the curve on receiver-operating characteristic curve analysis was 0.72 in predicting subsequent 3-point MACE in combined heart rate response to deep breathing and Valsalva ratio.Besides underlying coronary heart disease, the severity of cardiovascular autonomic neuropathy is strongly associated with subsequent 3-P MACE. Combined heart rate response to deep breathing and Valsalva ratio testing can increase sensitivity and specificity in predicting subsequent 3-point MACE, and it can serve as a time-effective cardiovascular autonomic screening service in the outpatient clinic sitting.

Purpose: Shunt procedures used to treat cryptococcal meningitis complicated with hydrocephalus and/or increased intracranial pressure (IICP) could result in cerebrospinal fluid (CSF) overdrainage, thereby presenting therapeutic challenges. Methods: We analyzed the clinical features and neuroimaging findings after the ventriculoperitoneal (VP) shunt procedure in 51 HIV (Human Immunodeficiency Virus)-negative patients with cryptococcal meningitis, to assess the risk factors associated with post-shunt CSF overdrainage. Results: Symptomatic CSF overdrainage occurred in 12% (6/51) of patients with cryptococcal meningitis who underwent the shunt procedure. Rapid deterioration of neurological conditions was found in 6 patients after the shunt procedure was performed, including disturbed consciousness, quadriparesis, and dysphasia in 5 patients and severe ataxia in 1. The mean duration of CSF overdrainage after the shunting procedure was 2–7 days (mean 4 days). The mean interval between meningitis onset to shunting procedure remained independently associated with CSF overdrainage, and the cut-off value for predicting CSF overdrainage in interval between meningitis onset to shunting procedure was 67.5 days. Conclusions: CSF overdrainage after the VP shunt procedure is not rare, especially in patients with a high-risk of cryptococcal meningitis who also have a prolonged duration of hydrocephalus and/or IICP. Keywords: CSF overdrainage, HIV-Negative cryptococcal meningitis, Outcome, Risk factor, Ventriculoperitoneal shunt procedures

Background A standard post-concomitant radiochemotherapy involving adjuvant temozolomide (TMZ) was stopped after 6 cycles for high-grade gliomas (HGG). Several studies demonstrated that prolonged TMZ treatment increased survival for these patients. Methods This retrospective study aimed to compare changes in tumor volume during and after adjuvant TMZ treatment and overall survival (OS). Results There were 90 patients were administered adjuvant TMZ treatment. Comparing average tumor volume changes during TMZ treatment and after TMZ was stopped, a significant decrease in tumor volume was observed during TMZ treatment in the total patient population, the anaplastic astrocytoma (AA) group, and the glioblastoma multiforme (GBM) group (P ≤ 0.001, P = 0.042, and P = 0.005, respectively). Median overall survival was 78.4 weeks, which was significant regarding the surgical tumor resection rate (r = 0.241; P = 0.04) and total TMZ treatment cycles (r = 0.631; P ≤ 0.001). Conclusions During adjuvant TMZ treatment, tumor volume decreased significantly (P = 0.042, and P = 0.005, respectively) in patients with GBM and AA. Prolonged TMZ administration improved OS, without increased toxicity.

Background The respiratory dysfunction of patients with Parkinson’s disease (PD) has drawn increasing attention. This study evaluated the relationship between gray matter volume (GMV), as determined by voxel-based morphometry (VBM), and respiratory dysfunction in patients with PD and correlated it with systemic inflammatory markers. Methods Whole-brain VBM analysis was performed on 3-dimensional T1-weighted images in 25 PD patients with abnormal pulmonary function (13 men, 12 women; mean age: 62.9 ± 10.8 years) and, for comparison, on 25 sex- and age-matched PD patients with normal pulmonary function (14 men, 11 women; mean age: 62.3 ± 6.9 years). Inflammatory markers were determined by flow cytometry. The differences and correlations in regional GMV, clinical severity and inflammatory markers were determined after adjusting for age, gender and total intracranial volume (TIV). Results Compared with the normal pulmonary function group, the abnormal pulmonary function group had smaller GMV in several brain regions, including the left parahippocampal formation, right fusiform gyrus, right cerebellum crus, and left postcentral gyri. Forced expiratory volume in 1 s (FEV1) and maximal expiratory flow after expiration of 50% of forced vital capacity (MEF50) were positively correlated with regional GMV. There were no significant differences in the level of serum inflammatory markers between two groups. Conclusion Our findings suggested that involvement of the central autonomic network and GM loss may underlie the respiratory dysfunction in PD patients.

To identify disease-related spatial covariance patterns of grey matter volume as an aid in the classification of Parkinson’s disease (PD). Seventy structural covariance networks (SCNs) based on grey matter volume covariance patterns were defined using independent component analysis with T1-weighted structural MRI scans (discovery sample, 70 PD patients and 70 healthy controls). An image-based classifier was constructed from SCNs using a multiple logistic regression analysis with a leave-one-out cross-validation-based feature selection scheme. A validation sample (26 PD patients and 26 healthy controls) was further collected to evaluate the generalization ability of the constructed classifier. In the discovery sample, 13 SCNs, including the cerebellum, anterior temporal poles, parahippocampal gyrus, parietal operculum, occipital lobes, supramarginal gyri, superior parietal lobes, paracingulate gyri and precentral gyri, had higher classification performance for PD. In the validation sample, the classifier had moderate generalization ability, with a mean sensitivity of 81%, specificity of 69% and overall accuracy of 75%. Furthermore, certain individual SCNs were also associated with disease severity. Although not applicable for routine care at present, our results provide empirical evidence that disease-specific, large-scale structural networks can provide a foundation for the further improvement of diagnostic MRI in movement disorders. • Disease-specific, large-scale SCNs can be identified from structural MRI. • A new network-based framework for PD classification is proposed. • An SCN-based classifier had moderate generalization ability in PD classification. • The selected SCNs provide valuable functional information regarding PD patients.

Reduced baroreflex sensitivity (BRS) has been reported in patients with acute cardiovascular events. We tested the hypothesis that BRS is substantially reduced in patients with spontaneous intracerebral hemorrhage (ICH) and that BRS can predict treatment outcomes.We examined BRS and other cardiovascular autonomic parameters in 35 patients with ICH over the course of 30 days. Cardiovascular autonomic parameters also were evaluated in 30 healthy volunteer subjects during the study period. Outcome was assessed at 30 days with the modified Rankin Scale (mRS). Good outcome was defined as an mRS1, whereas patients defined as having a poor outcome had either an mRS ≥2 or died shortly after the stroke event.Twenty patients had a poor outcome, and 15 patients had a good outcome. BRS values in the patients with poor outcome group were lower in comparison with the healthy subjects, and BRS values in patients with poor outcomes were significantly lower than that those in patients with good outcomes on day 1, day 4, and day 10. BRS was associated independently with outcome and the cut-off value of BRS on day 1 in the poor outcome group was 6.79.Based on our results, BRS value at admission is a more powerful predictor of outcome than the Glasgow Coma Scale score at admission. An assay of BRS could be added as a biomarker for outcome prediction among patients with spontaneous ICH in clinical practice.

Adult bacterial meningitis (ABM) caused by non-Pseudomonas (Ps.) aeruginosa Pseudomonas (NPAP) species infection has rarely been reported. The clinical characteristics of 52 cases of Pseudomonas ABM (11 NPAP- and 41 Ps. aeruginosa-related meningitis) collected during a 30-year study period (1986-2015) were included. Eleven cases of NPAP ABM were identified in the literature, and their clinical data were also collected. Therefore, a total of 22 NPAP ABM cases were enrolled. The clinical characteristics of the NPAP ABM and Ps. aeruginosa ABM groups were compared. Of the implicated NPAP strains, Ps. putida and Ps. stutzeri were the most common (7 cases each), followed by Ps. mendocina in 4, Ps. fluorescens in 1, Ps. fulva in 1, Ps. alcaligenes in 1, and Ps. mosselii in 1. Of the 22 cases, 50% (11/22) had an underlying postneurosurgical state. Fever (77.3%, 17/22) and altered consciousness (45.5%, 10/22) were the most common clinical presentations. Antibiotic non-susceptibility was found in 3 strains of Ps. putida and 1 Ps. mosselii strain. Compared to the patients with Ps. aeruginosa ABM, those with NPAP ABM had a higher incidence of spontaneous infections and a better survival rate. In conclusion, although Ps. putida, Ps. stutzeri and Ps. mendocina were the major implicated strains of NPAP ABM, the clinical characteristics of this specific group of ABM demonstrated marked heterogeneity. Even though the cases with NPAP ABM had better therapeutic results than those with Ps. aeruginosa ABM, further large-scale studies are needed to better delineate this specific group of ABM.

Osteoporosis is easily overlooked in male patients, especially in the field of rheumatic diseases mostly prevalent with female patients, and its link to pathogenesis is still lacking. Attenuated monocyte apoptosis from a transcriptome-wide expression study illustrates the role of monocytes in osteoporosis. This study tested the hypothesis that the monocyte percentage among leukocytes could be a biomarker of osteoporosis in rheumatic diseases. Eighty-seven males with rheumatic diseases were evaluated in rheumatology outpatient clinics for bone mineral density (BMD) and surrogate markers, such as routine peripheral blood parameters and autoantibodies. From the total number of 87 patients included in this study, only 15 met the criteria for diagnosis of osteoporosis. Both age and monocyte percentage remained independently associated with the presence of osteoporosis. Steroid dose (equivalent prednisolone dose) was negatively associated with BMD of the hip area and platelet counts were negatively associated with BMD and T score of the spine area. Besides age, monocyte percentage meets the major requirements for osteoporosis in male rheumatic diseases. A higher monocyte percentage in male rheumatic disease patients, aged over 50 years in this study, and BMD study should be considered in order to reduce the risk of osteoporosis-related fractures.

This paper aims to examine the effectiveness of structural imaging as an aid in the diagnosis of Parkinson’s disease (PD). High-resolution T 1-weighted magnetic resonance imaging was performed in 72 patients with idiopathic PD (mean age, 61.08 years) and 73 healthy subjects (mean age, 58.96 years). The whole brain was parcellated into 95 regions of interest using composite anatomical atlases, and region volumes were calculated. Three diagnostic classifiers were constructed using binary multiple logistic regression modeling: the (i) basal ganglion prior classifier, (ii) data-driven classifier, and (iii) basal ganglion prior/data-driven hybrid classifier. Leave-one-out cross validation was used to unbiasedly evaluate the predictive accuracy of imaging features. Pearson’s correlation analysis was further performed to correlate outcome measurement using the best PD classifier with disease severity. Smaller volume in susceptible regions is diagnostic for Parkinson’s disease. Compared with the other two classifiers, the basal ganglion prior/data-driven hybrid classifier had the highest diagnostic reliability with a sensitivity of 74%, specificity of 75%, and accuracy of 74%. Furthermore, outcome measurement using this classifier was associated with disease severity. Brain structural volumetric analysis with multiple logistic regression modeling can be a complementary tool for diagnosing PD.

Objectives:The condition of caregivers is important to the quality of care received by people with Parkinson’s disease (PD), especially at the late disease stages. This study addresses the distress placed on caregivers by participants’ neuropsychiatric symptoms at different stages of PD in TaiwanMethods:This prospective study enrolled 108 people with PD. All participants were examined with the Unified Parkinson’s Disease Rating Scale (UPDRS), Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), Cognitive Abilities Screening Instrument (CASI), and Clinical Dementia Rating (CDR) scale. Caregiver distress was measured using the Neuropsychiatric Inventory Caregiver Distress Scale (NPI-D). Statistical analysis was used to explore the PD-related factors that contribute to caregiver distress.Results:The mean follow-up interval in the 108 PD participants were 24.0 ± 10.2 months with no participant lost to follow-up due to death. NPI-distress (the sum of NPI caregiver distress scale across the 12 domains of the NPI) was positively correlated with NPI-sum (the total score across the 12 domains of the NPI) (r = 0.787, p < 0.001), CDR (r = 0.403, p < 0.001), UPRDS (r = 0.276, p = 0.004), and disease duration (r = 0.246, p = 0.002), but negatively correlated with CASI (r = −0.237, p = 0.043) and MMSE (r = −0.281, p < 0.001). Multiple linear regression analysis showed that only NPI-sum and disease duration were independently correlated with NPI-distress.Conclusion:The disease duration and NPI-sum are independent predictors of caregiver distress in Taiwanese populations with PD. Early detection and reduction of neuropsychiatric symptoms in people with PD can help decrease caregiver distress.

Background Acute traumatic cervical spinal cord injury (SCI) is a leading cause of disability in adolescents and young adults worldwide. Evidence from previous studies suggests that circulating cell-free DNA is associated with severity following acute injury. The present study determined whether plasma DNA levels in acute cervical SCI are predictive of outcome. Methods In present study, serial plasma nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) levels were obtained from 44 patients with acute traumatic cervical SCI at five time points from day 1 to day 180 post-injury. Control blood samples were obtained from 66 volunteers. Results Data showed a significant increase in plasma nDNA and mtDNA concentrations at admission in SCI patients compared to the control group. Plasma nDNA levels at admission, but not plasma mtDNA levels, were significantly associated with the Japanese Orthopaedic Association (JOA) score and Injury Severity Score in patients with acute traumatic cervical SCI. In patients with non-excellent outcomes, plasma nDNA increased significantly at days 1, 14 and 30 post-injury. Furthermore, its level at day 14 was independently associated with outcome. Higher plasma nDNA levels at the chosen cutoff point (> 45.6 ng/ml) predicted poorer outcome with a sensitivity of 78.9% and a specificity of 78.4%. Conclusions These results indicate JOA score performance and plasma nDNA levels reflect the severity of spinal cord injury. Therefore, the plasma nDNA assays can be considered as potential neuropathological markers in patients with acute traumatic cervical SCI.

Objective. As cell-free DNA levels in the pleural fluid and serum of parapneumonic pleural effusion (PPE) patients have not been thoroughly explored, we evaluated their diagnostic potential. Methods. Twenty-two PPE and 16 non-PPE patients were evaluated. Serum and pleural fluids were collected, and cell-free DNA was quantified. All biomarkers were assessed for correlation with days after admission. Receiver operating characteristic (ROC) curve analysis was used to determine diagnostic accuracy and optimal cut-off point. Results. Nuclear and mitochondrial DNA levels in the pleural fluid and nuclear DNA levels in serum of PPE patients were significantly higher than in those of the non-PPE patients. However, only cell-free DNA levels in pleural fluid correlated with days after admission among PPE patients (r= 0.464, 0.538, respectively). ROC curve analysis showed that nuclear and mitochondrial DNA in pleural fluid had AUCs of 0.945 and 0.889, respectively. With cut-off values of 134.9 and 17.8 ng/ml for nuclear and mitochondrial DNA in pleural fluid, respectively, 96% sensitivity and 81% specificity were observed for PPE diagnosis. Conclusion. Nuclear and mitochondrial DNA in pleural fluid possess PPE diagnostic potential and correlated with disease severity. Serum nuclear DNA could also be used to distinguish freshly admitted PPE patients (Day 1) from non-PPE patients, but with less accuracy.

Cryptococcal meningitis (CM) is a serious infectious disease of the central nervous system, and associated brain injuries can be found in the very early stage of disease. In this study, 92 adult CM patients (59 men, 33 women; median age 54.66 years, range 20–86 years) were enrolled, and their clinical, laboratory, neuroimaging features and therapeutic outcomes were analyzed. Two main clinical comparative analyses of the clinical characteristics and laboratory and neuroimaging features were made in this study. The first compared clinical differences between the survivors and non-survivors of all enrolled patients, and the second compared differences between the following three groups: Group I, the patients who died within 14 days of initiating treatment; Group II, the patients who died within 15 days to 1 year of initiating treatment, and Group III, the patients who survived for more than 1 year after initiating treatment. Prognostic factors including initial altered consciousness, increased cerebrospinal fluid (CSF) lactate level and the presence of cryptococcemia were significantly different between the different groups. The patients with early mortality had a higher CSF lactate level and higher rate of cryptococcemia. The presence of cryptococcemia was an important prognostic factor, and the patients with cryptococcemia had a higher incidence of positive CSF India ink stain. Further large-scale studies are needed to delineate the clinical and laboratory features of CM patients with early mortality.

Background. Reduced baroreflex sensitivity (BRS) has been reported in patients with acute cardiovascular events. We tested the hypothesis that BRS varies in different subtypes of acute ischemic stroke (AIS) and that BRS is a predictor of clinical outcomes. Methods. We examined autonomic parameters in 34 patients with AIS, including the small deep hemisphere infarction, the large hemisphere infarction, and the brainstem infarction groups on Day 1, Day 7, and Day 30 after AIS. Autonomic parameters were also evaluated in 18 age- and sex-matched healthy volunteers as a control group. The clinical outcomes were analyzed using the modified Rankin scale at 30 days after stroke. Results. The BRS, Valsalva ratio, and heart rate response to deep breathing (HR-DB) were significantly lower in patients after AIS on admission than in controls (ppp Conclusion. Beside NIHSS score on admission, BRS is a potential prognostic factor of 1-month outcomes in patients with AIS. Patients with large hemisphere infarction or brainstem infarction have more blunting BRS than do those with lacunar infarction, which provides some insight into which patients may be expected to have a poor outcome.

Objective Both diabetic distal symmetrical polyneuropathy (DSPN) and cardiac autonomic neuropathy (CAN) indicate the length-dependent pattern of disease. Decreased parasympathetic activity has been found in the early phase of CAN and sural sensory nerve action potential (SNAP) imply axonal loss in DSPN. Method All patients with type 2 diabetes underwent cardiovascular autonomic function and nerve conduction studies (NCS). We constructed modified composite autonomic scoring scale (CASS) and composite score of NCS to measure the severity of CAN and DSPN, respectively. Results Patients with a longer duration of diabetes had a lower heart rate response to deep breathing (HR_DB), Valsalva ratio (VR), and baroreflex sensitivity (BRS), higher CASS, a higher percentage of CAN, lower sural SNAP, higher composite score of NCS, and a higher percentage of DSPN. Multiple linear regression analysis showed that only sural SNAPs were independently associated with mean HR_DB. Conclusion Sural SNAP was closely correlated with parameters of cardiovagal functions in patients with different durations of diabetes. The percentage and severity of CAN and DSPN increase with longer duration of diabetes. Significance The independent association of sural sensory nerve action potential amplitude and heart rate response to deep breathing with type 2 diabetes is important because combined testing increases diagnostic sensitivity and specificity.

Background Septic acute kidney injury (AKI) is a common complication of severe sepsis. We tested the hypothesis that serum cell adhesion molecule levels are substantially increased in early septic AKI and decreased after antimicrobial therapy and their level can predict prognosis. Methods Seventy-two nontraumatic, nonsurgical adult patients with severe sepsis admitted to the emergency department were evaluated. Serum adhesion molecules were collected and assessed. We evaluated their relationship with early septic AKI compared with other clinical predictors and biomarkers. Results Forty-five patients (62.5%) experienced early septic AKI. Patients with septic AKI also were more likely to experience septic shock and respiratory failure and had higher in-hospital mortality. Stepwise logistic regression model revealed that E-selectin level, septic shock, and respiratory failure were independently associated with septic AKI and each 1 ng/ml increase in serum E-selectin level increased the risk of septic AKI by 1%. Furthermore, the E-selectin levels in the septic AKI group were significantly higher than those in the non-AKI group at two different times (days 1 and 4). Conclusion WE show that early septic AKI implies a higher mortality in severe sepsis patients and that E-selectin level at presentation is a powerful predictor of early septic AKI.

Background Oxidative stress is thought to participate in the pathobiology of secondary brain injury after acute traumatic brain injury (TBI). This study posits that oxidative stress levels in acute TBI are predictive of outcome. Methods Two hundred and twenty-nine blood samples from 88 patients admitted within 24 hours after TBI were obtained on admission and on days 4 and 7. Serial plasma oxidative level and antioxidant were examined in 88 patients with acute TBI and 27 control individuals. Results Compared with controls, patients with TBI had significantly increased serum glutathione (GSH) levels on presentation and significantly decreased erythrocyte superoxide dismutase levels. Outcome was assessed on discharge using the Glasgow Outcome Scale. Serum GSH and erythrocyte superoxide dismutase levels were significantly higher in the good outcome group than in the poor outcome group on day 1 ( P = 0.008 and P = 0.026, respectively). In the logistic regression analysis, only motor deficits and GSH levels on presentation were independently associated with outcome. A GSH cutoff value of 1.106 μmol/L on presentation was associated with good outcome in patients with acute TBI. Conclusions Quantifying biomarkers of oxidative stress and antioxidant status of serum correlate with trauma severity and may be used to predict outcomes after TBI. Higher serum GSH levels on admission are associated with better outcome.

Autonomic disorders have been recognized as an important non-motor feature in Parkinson&rsquo, s disease (PD). However, there is a paucity of information on the presence and severity of cardiovascular autonomic neuropathy (CAN) among different motor phenotypes. The aims of this study were to examine the feasibility of electrochemical skin conductance (ESC) measured by Sudoscan as a screening service for CAN in patients with PD and investigate the severity of CAN among different motor phenotypes. Design: This was a cross-sectional observational study that enrolled 63 patients with PD. Patients were divided into three phenotypes, postural instability/gait difficulty (PIGD), tremor-dominant (TD), and akinetic-rigid (AR), according to their motor symptoms. Cardiovascular autonomic function was measured, and the presence and severity of CAN was determined according to the composite autonomic scoring scale (CASS). Functional scores were measured by the Hoehn and Yahr (HY) stage and the Unified Parkinson&rsquo, s Disease Rating Scale (UPDRS). The median HY stage was 2.0 [1.5, 3.0]. Median UPDRS total score was 23.0 (17.5, 30.5), 10.0 (6.0, 11.0) and 14.0 (6.3, 23.8) in groups of PIGD, TD and AR, respectively (p = 0.001). Mean CASS was 1.7 &plusmn, 1.3, 0.6 &plusmn, 0.4, and 1.8 &plusmn, 1.5 in groups of PIGD, TD and AR, respectively (p = 0.204). Although the ESC was not strongly associated with the cardiovascular autonomic parameters, the CAN risk score provided by Sudoscan significantly correlated with parameters of cardiovascular autonomic function, including heart rate response to deep breathing (HR_DB), Valsalva ratio (VR), and baroreflex sensitivity (BRS). By receiver-operating characteristic (ROC) analysis, if a patient&rsquo, s CAN risk score is higher than 33.5 (%), it is recommended to be aware of the presence of CAN even in PD patients who are asymptomatic. The area under ROC curve was 0.704. Based on our results, CAN risk score may be used for screening of CAN in patients with PD before resorting to the more sophisticated and specific, but ultimately more time-consuming, complete autonomic function testing.

Purpose: Oxidative stress has been shown to reflect on the development of sepsis and disease severity. In the present study, we evaluated the effects of increased levels of oxidative stress and decreased antioxidant coactivity in patients with sepsis, and the importance of oxidative stress on treatment outcomes. Methods: Biomarkers of oxidative stress (thiobarbituric acid-reactive substances [TBARS]) and antioxidant capacity (glutathione peroxidase [GPx] and glutathione content [thiol]) were prospectively evaluated along with biochemical and clinical data in 100 patients with sepsis on days 1, 4, and 7 after admission. Results: The TBARS level of the non-survivor group was significantly higher than that of the survivor group on day 1 and day 4 and negatively correlated with thiol upon admission. However, thiol was positively correlated with lactate concentration. The TBARS and lactate levels upon admission were independent predictors of fatality. Conclusions: We conclude that a TBARS cut-off value of 18.30 μM can be used to predict fatality, and an increase in the TBARS concentration by 1 μM will increase the fatality rate by 0.94%. In the panel of biomarkers, the TBARS assay can be considered as a prognostic biomarker for the treatment of patients with sepsis.

To investigate the clinical characteristics, laboratory features and prognostic factors of elderly patients with postneurosurgical bacterial meningitis.Five hundred and forty patients with adult bacterial meningitis (ABM) were collected from 1986-2015, of whom 167 were ≥ 65 years. Of these 167 elderly patients, 82 had postneurosurgical infections and 85 had spontaneous infections. Clinical, laboratory and therapeutic data of these two groups were compared.The 82 elderly ABM patients with postneurosurgical infections included 48 men and 34 women with a median age of 71 years (range: 65-84 years). In addition to the postneurosurgical condition, the other most common underlying conditions included diabetes mellitus (29.3%) and hydrocephalus (29.3%). The major clinical presentations were fever (80.5%), altered consciousness (50.0%), hydrocephalus (43.9%), seizure (24.4%) and septic shock (15.9%). Of the implicated pathogens, staphylococcal species (spp.) were the most common (31.7%), followed by Acinetobacter spp. (12.2%), Enterobacter spp. (7.3%), Pseudomonas spp. (7.3%), Enterococcus faecalis (7.3%) and Escherichia coli (6.1%). The implicated staphylococcal spp. had a high rate of non-susceptibility to methicillin (84.6%), and the implicated Acinetobacter spp. and Enterobacter spp. had non-susceptible rates to ceftazidime of 60% and 50%, respectively. The mortality rate was 28.1%, and septic shock was the most significant prognostic factor. Compared with the clinical characteristics of the other 85 elderly patients with spontaneous ABM, there were significant differences in underlying condition, clinical and laboratory features and therapeutic outcomes.Elderly patients accounted for 30.9% of all cases of ABM, of whom 49.1% had postneurosurgical ABM. The clinical characteristics of the elderly patients with postneurosurgical ABM were non-specific, and cerebrospinal fluid studies were needed to confirm the diagnosis. The mortality rate of this group of patients was high, and septic shock was an important prognostic factor. The clinical and laboratory features and therapeutic outcomes were different between the elderly patients with postneurosurgical and spontaneous ABM.

Objective Depressed baroreflex sensitivity (BRS) is reported in obstructive sleep apnea (OSA). Improvement of BRS short-term after surgical treatment is also reported. We tested the hypothesis that surgical treatment not only improves clinical outcomes, but also improves BRS after 18 months. Methods Cardiovascular autonomic tests, polysomnography (PSG), and biochemical testing were prospectively evaluated in 54 OSA patients at three time points (preoperatively, 6 months and 18 months postoperatively) and compared with 20, age- and body mass index (BMI)-matched, healthy controls. Results The BRS increased after surgical treatment at 18-month follow-up, with results similar to the healthy control. Additionally, average O2, mO2 Conclusions Besides improvement in clinical outcomes, depressed BRS in OSA patients is reversible and these patients have the potential for total recovery of baroreflex function after 18 months of treatment.

Although corticosteroids are an effective anti-inflammatory adjuvant therapy, the role of adjunctive steroid therapy in treating adult bacterial meningitis in Taiwan remains controversial.Cases of acute bacterial meningitis were identified from the annual hospitalization discharge claims of the National Health Insurance Research Database using International Classification of Diseases, Ninth Revision codes from January 2000 to December 2013. Patients were classified into two groups: (1) steroid group (adjunctive steroids and empirical antibiotics) and (2) placebo group (empirical antibiotics only).There were 15,037 patients enrolled in this study; of these, 57% (7175/15,037) and 52% (7862/15,037) were placed in the placebo and steroid groups, respectively. The case-fatality rates were 11.5% (826/7175) in the placebo group and 19.9% (1562/7862) in the steroid groups during hospitalization (P = 0.77). Further, the hazard ratio (relative to placebo group) of in-hospital and one-year case fatality rate were 0.923 (95% confidence interval [CI]: 0.846-1.007, P = 0.073) and 1.514 (95% CI: 1.425-1.608, P 0.0001) according to the multivariate Cox model after adjustment for age and sex.On the basis of these results, steroid group had a more fulminant clinical course (e.g., acute respiratory failure and pneumonia, etc.), and unfavorable outcomes than placebo group. Therefore, more prospective, randomized, double-blind trials are warranted to evaluate the efficacy of adjunctive steroid therapy in treating adult bacterial meningitis in Taiwan.

To investigate the structural changes of the brain that correlate with physical frailty and cognitive impairments in Parkinson’s disease (PD) patients. Sixty-one PD patients and 59 age- and sex-matched healthy controls were enrolled. For each participant, a frailty assessment using Fried’s criteria and comprehensive neuropsychological testing using the Wechsler Adult Intelligence Scale-III and Cognitive Ability Screening Instrument were conducted, and structural brain MR images were acquired for voxel-based morphometric analysis. The neuropsychological testing includes various tests in these five domains: attention, executive, memory, speech and language, and visuospatial functions. Exploratory group-wise comparisons of gray matter volume (GMV) in the PD patients and controls were conducted. Voxel-wise multiple linear regression analyses were conducted for physical frailty–related and cognitive impairment–related GMV changes in the PD patients. Voxel-wise multiple linear regressions were also performed with the five cognitive domains separated using the same model. The PD patients exhibited diffuse GMV reductions in comparison to the controls. In the PD patients, physical frailty–related decreases in GMV were observed in the bilateral frontal and occipital cortices, while cognitive impairment–related decreases in GMV were observed in the bilateral frontal, occipital, and temporal cortices. These regions overlap in the lateral occipital cortex. After the five domains of cognitive functions were analyzed separately, physical frailty–related decreases in GMV still overlap in lateral occipital cortices with every domain of cognitive impairment–related decreases in GMV. Reduced GMV in the lateral occipital cortex is associated with cognitive impairment and physical frailty in PD patients. • Physical frailty in PD was associated with decreased GMV in the frontal and occipital cortices, while cognitive impairment was associated with decreased GMV in the frontal, temporal, and occipital cortices. • Physical frailty and cognitive impairment were both associated with decreased GMV in the lateral occipital cortex, which is part of the ventral object-based visual pathway. • Decreased GMV in the lateral occipital cortex may serve as a potential imaging biomarker for physical frailty and cognitive impairment in PD.

Background Endothelial dysfunction plays a central role in severe sepsis. Endocan is constitutively expressed in human endothelial cells when sepsis occurs. We tested the hypothesis that endocan concentrations are substantially increased in severe sepsis and decrease after antimicrobial therapy, and that endocan concentrations can predict treatment outcomes. Methods Biomarkers of the endothelium including endocan and cell adhesion molecules were prospectively evaluated in 153 patients with severe sepsis on days 1, 4, and 7 after admission along with biochemical and clinical data. Results Sepsis non-survivors had significantly higher endocan, ICAM-1, and VCAM-1 concentrations and lower platelet concentrations upon admission than the survivors. Non-survivors had significantly higher endocan and VCAM-1 concentrations than the survivors on serial analysis (days 1, 4, and 7). After stepwise logistic regression model and AUC analysis, endocan was revealed as a good predictor of outcome in severe sepsis, and the cut-off value for predicting fatality was 6.28 ng/ml. An increase in the endocan concentration by one ng/ml indicated an increase in fatality rate by 11.1%. Conclusions Based on our results, serial endocan concentration meets the major requirements for predicting outcome in patients with severe sepsis. An assay of endocan concentration may be a good prognostic biomarker in the clinic for severe sepsis.

Background To identify the vulnerable areas associated with systemic oxidative stress and further disruption of these vulnerable areas by measuring the associated morphology and functional network alterations in Parkinson’s disease (PD) patients with and without cognitive impairment. Methods This prospective study was approved by the institutional review board of KCGMH, and written informed consent was obtained. Between December 2010 and May 2015, 41 PD patients with different levels of cognitive functions and 29 healthy volunteers underwent peripheral blood sampling to quantify systemic oxidative stress, as well as T1W volumetric and resting state functional MRI (rs-fMRI) scans. Rs-fMRI was used to derive the healthy intrinsic connectivity patterns seeded by the vulnerable areas associated with any of the significant oxidative stress markers. The two groups were compared in terms of the functional connectivity correlation coefficient (fc-CC) and gray matter volume (GMV) of the network seeded by the vulnerable areas. Results The levels of oxidative stress markers, including leukocyte apoptosis and adhesion molecules, were significantly higher in the PD group. Using whole-brain VBM-based correlation analysis, the bilateral mesial temporal lobes (MTLs) were identified as the most vulnerable areas associated with lymphocyte apoptosis (P

Purpose To evaluate the correlation between microstructural damage in the corpus callosum (CC) and the cognitive performance of patients with or without delayed encephalopathy (DE) after carbon monoxide (CO) intoxication in the chronic stage. Methods Diffusion tensor imaging (DTI) was performed more than 6 months after CO intoxication for 10 patients with DE and 10 patients without DE recruited from out-patient clinics, as well as for 15 normal controls (NCs). Using a probabilistic tractography method to parcel the CC based on fiber projections to cortical connectivity patterns, the DTI indices were calculated in the CC subregions and further correlated with cognitive performance. Results The DE group exhibited significantly lower fractional anisotropy (FA) and higher radial diffusivity (RD) values in the prefrontal, premotor, primary motor, primary sensory, parietal, and occipital CC subregions than did the NCs. The DE group also exhibited significantly lower FA values in the prefrontal and premotor subregions than did the non-DE group. Lower FA and higher RD values in the CC subregions were associated with poorer scores on the symbol search test. Conclusions CO intoxication may cause lower FA and higher RD in the CC subregions, with subsequent cognitive impairment. This finding suggests that selective CC damage after CO intoxication is more profound in patients with DE.

STUDY OBJECTIVES To evaluate white matter integrity in patients with obstructive sleep apnea (OSA) using diffusion tensor imaging (DTI) and to assess its relationship with systemic inflammation. DESIGN Cross-sectional study. SETTING One tertiary medical center research institute. PATIENTS OR PARTICIPANTS Twenty patients with severe OSA (apnea-hypopnea index [AHI] > 30, 18 men and 2 women) and 14 healthy volunteers (AHI < 5, 11 men and 3 women). INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Patients with severe OSA and healthy volunteers underwent polysomnography to determine the severity of sleep apnea, and DTI scanning to determine fiber integrity. Early or late phase changes in leukocyte apoptosis and its subsets were determined by flow cytometry. DTI-related indices (including fractional anisotropy [FA], axial diffusivity [AD], radial diffusivity [RD], and mean diffusivity [MD]) were derived from DTI. The FA maps were compared using voxel-based statistics to determine differences between the severe OSA and control groups. The differences in DTI indices, clinical severity, and leukocyte apoptosis were correlated after adjusting for age, sex, body mass index, and systolic blood pressure. Exploratory group-wise comparison between the two groups revealed that patients with OSA exhibited low FA accomplished by high RD in several brain locations, without any differences in AD and MD. The FA values were negatively correlated with clinical disease severity and leukocyte early apoptosis. CONCLUSIONS Obstructive sleep apnea impairs white matter integrity in vulnerable regions, and this impairment is associated with increased disease severity. The possible interactions between systemic inflammation and central nervous system microstructural damage may represent variant hypoxic patterns and their consequent processes in OSA.

Background and aim Cell apoptosis in critically ill patients plays a pivotal role in the pathogenesis of sepsis. This study aimed to determine the prognostic value of leukocyte apoptosis in patients with severe sepsis. Methods Leukocyte apoptosis was determined by flow cytometry. The values of annexin V, APO2.7, and 7-amino-actinomycin D (7AAD) for each subtype of leukocyte were analyzed in 87 patients with severe sepsis and 27 controls. Results The percentages of apoptosis (APO2.7 [%]) in the leukocyte subsets were significantly higher in the patients with severe sepsis than in the controls. The percentages of APO2.7 in leukocyte apoptosis, APO2.7 in lymphocytes apoptosis, and annexin V + 7AAD in monocytes apoptosis were significantly higher in non-survivors than in survivors. Levels of APO2.7 in lymphocytes apoptosis, annexin V + 7AAD in monocytes apoptosis, and serum lactate were all independently predictive of mortality. Conclusion Leukocyte apoptosis is significantly higher in patients with severe sepsis. The percentages of late lymphocyte and monocyte apoptosis may be predictive of outcome in such patients. Aside from serum lactate, APO2.7 level in lymphocyte apoptosis is also a useful predictor of outcome on admission to the emergency department.

Anaerobic infection is a very uncommon condition in adult bacterial meningitis (ABM), and its clinical characteristics have yet to be clarified. We enrolled 540 patients with culture-proven bacterial meningitis during a study period of 30 years (1986–2015), of whom 13 (2.4%) had anaerobic infections. These 13 patients were eight men and five women, aged 22–77 years. Among them, 53.8% (7/13) had a postneurosurgical state as the preceding event, and 79.6% (10/13) had underlying medical conditions including diabetes mellitus, malignancy, liver cirrhosis, cerebral infarct and alcoholism. Nosocomial and mixed infections were found in 15.5% (2/13) and 46.1% (6/13) of the patients, respectively. A total of 14 anaerobic strains were isolated from cerebrospinal fluid specimens, including nine Gram-negative (G(−)) strains: Fusobacterium nucleatum (3), Prevotella species (3) and Bacteroides fragilis (3), and five Gram-positive (G(+)) strains: Propionibacterium acnes (3) and Peptostreptococcus micros (also known as Parvimonas micra) (2). All of the implicated G(+) anaerobic bacteria were susceptible to penicillin, and no multiple drug-resistant strains were found among the implicated G(−) anaerobic bacteria. Despite treatment, 30.8% (4/13) of the patients died. Of the nine survivors, 22.2% (2/9) had a full recovery, while the other 77.8% (7/9) had varying degrees of neurological deficits. Compared with the good outcome group (n = 6, modified Rankin scale (mRS) scores: 0–2), the poor outcome group (n = 7, mRS scores ≧3) had higher incidence of seizure. These results may offer a preliminary view of the clinical characteristics of anaerobic ABM.

Background Systemic inflammation and white matter (WM) alterations have been noted as effects of Parkinson’s disease (PD). This study sought to evaluate WM integrity in PD patients using diffusion tensor imaging (DTI) and to assess its relationship with systemic inflammation. Methods Sixty-six patients with PD (23 men and 43 women) and 67 healthy volunteers (29 men and 38 women) underwent blood sampling to quantify inflammatory markers and DTI scans to determine fiber integrity. The inflammatory markers included leukocyte apoptosis, as well as cellular and serum adhesion molecules, in each peripheral blood sample. DTI-related indices [including fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD)] were derived from DTI scans. The resulting FA maps were compared using voxel-based statistics to determine differences between the PD and control groups. The differences in the DTI indices, clinical severity, and inflammatory markers were correlated. Results Exploratory group-wise comparison between the two groups revealed that the PD patients exhibited extensive DTI index differences. Low FA accompanied by high RD and MD, without significant differences in AD, suggesting a demyelination process, were found in the parietal, occipital, cerebellar, and insular WM of the PD patients. The declined DTI indices were significantly correlated with increased clinical disease severity, adhesion molecules, and leukocyte apoptosis. Conclusions Patients with PD experience WM integrity damage in vulnerable regions, and these impairments are associated with increased disease severity and systemic inflammation. The possible interactions among them may represent variant neuronal injuries and their consequent processes in PD. Electronic supplementary material The online version of this article (doi:10.1186/s12868-017-0367-y) contains supplementary material, which is available to authorized users.

Serum adhesion molecules play a pivotal role in the pathogenesis of sepsis syndrome. This study aimed to evaluate the prognostic value of serum adhesion molecules in patients with severe sepsis and mechanical ventilation (MV) at the emergency department.Eighty-seven consecutive patients with severe sepsis, including 35 with MV, were evaluated. Serum samples were collected for analysis of serum adhesion molecules. The patients' clinical and laboratory data on admission were also recorded.The maximum 24-h APACHE II and 24-h SOFA scores were significantly higher in the severe sepsis patients requiring MV than in patients without MV (p=0.02 and p0.001). Mortality rate was significantly higher in severe sepsis patients requiring MV than in patients without MV (40% [14/35] vs. 9.6% [5/52], p=0.001). Both VCAM-1 level (p=0.03) and lactate concentration (p=0.04) on admission had significant differences between survivors and non-survivors in patients requiring MV. In the logistic regression model, only VCAM-1 level (p=0.049) was independently predictive of mortality. By correlation analysis, lactate concentration significantly correlated with the mean VCAM-1 level on admission (γ=0.484, p=0.004). The area under the ROC curve for VCAM-1 level was 0.747 (p=0.02, 95% CI: 0.576-0.918). The cut-off value of VCAM-1 level for predicting hospital mortality in severe sepsis patients receiving MV was 1870ng/mL, with 77% sensitivity and 71% specificity; then the likelihood ratio equals 2.7.In this study, VCAM-1 level is a more powerful outcome predictor of hospital mortality in severe sepsis patients requiring MV than lactate concentration and other conventional parameters on admission. This suggests that increased plasma VCAM-1 concentration may be useful in identifying who are at risk of hospital mortality among severely septic patients requiring MV.

Increased plasma deoxyribonucleic acid (DNA) levels may be associated with disease severity after acute traumatic brain injury (TBI). This study posits that increased plasma DNA levels in acute TBI are predictive of outcome. Both serial plasma nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) levels were examined in 88 consecutive patients with acute TBI and 66 control subjects. Additional samples were obtained on day 4 and day 7. Results showed that plasma nDNA and mtDNA on admission were significantly increased in patients with TBI compared with controls. Plasma nDNA, but not plasma mtDNA, levels in patients with acute TBI significantly correlated with Glasgow Coma Scale (GCS) score and Injury Severity Score (ISS) on presentation. Plasma nDNA increased significantly from day 1 to day 7 in patients with poor outcome. Its levels on presentation were independently associated with outcome and higher levels (cutoff value72.95 ng/mL) were associated with poorer outcomes. These findings suggest plasma nDNA levels reflect the severity of cerebral damage and can be considered a neuropathologic marker of patients with acute TBI. Further studies with bigger patient populations are warranted for better unbiased comparison.

Purpose Fall-related fracture is one of the most disabling features of idiopathic Parkinson's disease (PD). A better understanding of the associated factors is needed to predict PD patients who will require treatment. Methods This prospective study enrolled 100 adult idiopathic PD patients. Stepwise logistic regressions were used to evaluate the relationships between clinical factors and fall-related fracture. Results Falls occurred in 56 PD patients, including 32 with fall-related fractures. The rate of falls in the study period was 2.2 ± 1.4 per 18 months. The percentage of osteoporosis was 34% (19/56) and 11% in PD patients with and without falls, respectively. Risk factors associated with fall-related fracture were sex, underlying knee osteoarthritis, mean Unified Parkinson's Disease Rating Scale score, mean Morse fall scale, mean Hoehn and Yahr stage, and exercise habit. By stepwise logistic regression, sex and mean Morse fall scale were independently associated with fall-related fracture. Females had an odds ratio of 3.8 compared to males and the cut-off value of the Morse fall scale for predicting fall-related fracture was 72.5 (sensitivity 72% and specificity 70%). Discussion Higher mean Morse fall scales (>72.5) and female sex are associated with higher risk of fall-related fractures. Preventing falls in the high-risk PD group is an important safety issue and highly relevant for their quality of life.

Objectives. This study investigated serum thiobarbituric acid-reactive substances (TBARS) and free thiol levels in different subtypes of acute ischemic stroke (AIS) and evaluated their association with clinical outcomes.Methods. This prospective study evaluated 100 AIS patients, including 75 with small-vessel and 25 with large-vessel diseases. Serum oxidative stress (TBARS) and antioxidant (thiol) were determined within 48 hours and days 7 and 30 after stroke. For comparison, 80 age- and sex-matched participants were evaluated as controls.Results. Serum TBARS was significantly higher and free thiol was lower in stroke patients than in the controls on days 1 and 7 after AIS. The level of free thiol was significantly lower in the large-vessel disease than in the small-vessel disease on day 7 after stroke. Using the stepwise logistic regression model for potential variables, only stroke subtype, NIHSS score, and serum TBARS level were independently associated with three-month outcome. Higher TBARS and lower thiol levels in the acute phase of stroke were associated with poor outcome.Conclusions. Patients with large-vessel disease have higher oxidative stress but lower antioxidant defense compared to those with small-vessel disease after AIS. Serum TBARS level at the acute phase of stroke is a potential predictor for three-month outcome.

Apoptosis of both brain neurons and peripheral blood leukocyte is believed to be an important biomarker for evaluating the functional status of Parkinson’s disease (PD). However, their correlation remains unknown. A better understanding of the pathophysiology of neurodegeneration is essential for the treatment and prevention of PD. The present study demonstrated that leukocyte apoptosis is significantly higher in PD patients and is associated with central dopamine neuron loss by usingTc99m-TRODAT-1 SPECT. The leukocyte apoptosis and striatal dopamine transporter uptake ratios were further associated with increased severity and longer duration of disease. The interaction between brain and systemic inflammation may be responsible for the neurodegenerative disease progression.

Background and Aim. The sensitivity and specificity of biomarkers used for predicting peripheral neuropathy of Sjogren’s syndrome (SJS) patients remain unsatisfactory. This study aimed to determine the prognostic value of circulating autoantibodies levels in SJS patients with peripheral neuropathy.Methods. Two hundred and fifty serological positive (either anti-Ro or anti-La positive) SJS patients’ data were collected retrospectively. The titers of autoantibodies, electrophysiology reports, and clinical manifestation were reviewed.Results. The prevalence rate of peripheral neuropathy is 7.2% in our study. Regarding classification of peripheral neuropathy, 12 had mixed sensorimotor polyneuropathy, six had cranial neuropathy. After stepwise logistic regression analysis, anti-β2 glycoprotein I (aβ2GP I) and perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) were significantly associated with peripheral neuropathy in serology positive SJS (P=0.01,P=0.046, resp.).Conclusion. The occurrence of peripheral neuropathy among SJS patients is not frequent and easily overlooked. Our study demonstrated that aβ2GP I and p-ANCA levels may imply the danger of the occurrence of neuropathy in SJS patients, and they can be considered a biomarker that should be added to the panel of conventional autoantibody in SJS patients.

The purpose of this study is to analyze recent epidemiologic trend of adult bacterial meningitis (ABM) in Taiwan. The clinical features, laboratory data and therapeutic outcomes of 157 patients with ABM from 2006-2015 were analyzed. The results were compared with those of our previous two epidemiologic studies of ABM (1st study: 202 cases, January 1986-June 1999; 2nd study: 181 cases, July 1999-December 2005). Of the 157 patients with ABM, 96 were men and 61 women, and 68.2% (107/157) of them had a postneurosurgical state as the underlying condition. Monomicrobial infections and mixed infections were found in 92.4% (145/157) and 7.6% (12/145) of the cases, respectively. Of the implicated pathogens of monomicrobial infections, staphylococcal species were the most common, accounting for 27.6% (40/145) of them and Klebsiella species were the second common accounting for 13.8% (20/145) of them. The other common Gram-negative pathogens were Pseudomonas species and Acinetobacter species, accounting for 10.3% (15/145) and 7.6% (11/145), respectively. The overall mortality rate was 25.5% (40/157), and septic shock and liver cirrhosis were significant prognostic factors. This study revealed a change in the epidemiologic trend of ABM and the study results may offer important information for clinicians managing patients with ABM.