Serial plasma DNA levels as predictors of outcome in patients with acute traumatic cervical spinal cord injury.

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.

Anti-CCP-positive patients with RA have a higher 10-year probability of fracture evaluated by FRAX®: a registry study of RA with osteoporosis/fracture.

BACKGROUND: Positive anticyclic citrullinated peptide (anti-CCP+) is associated with bone loss in patients with rheumatoid arthritis (RA). However, whether overall positivity or specific levels of anti-CCP are associated with prevalent fracture or a 10-year probability of fracture remains unclear. METHODS: This interim analysis of an RA registry was conducted at Chang Gung Memorial Hospital in Kaohsiung (CGMHK) for RA-related osteoporosis/fracture. Consecutive patients with RA who had visited the rheumatology clinic at CGMHK since September 1, 2014, and fulfilled the classification criteria of RA were enrolled. The demographics, disease duration, Disease activity in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR), lifestyle, evidence of previous fracture, risk factors of fracture in the Fracture Risk Assessment Tool (FRAX®), and FRAX® score of each participant were collected. Anti-CCP, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and bone mineral density (BMD) were measured at enrollment. The patients were grouped by positivity or quartiles of anti-CCP level (I-IV). RESULTS: Five hundred twenty-one patients with RA were enrolled through May 31, 2016. In total, 359 (68.9%) patients were anti-CCP+. Compared with anti-CCP- patients, anti-CCP+ patients had a significantly higher DAS28-ESR (p = 0.0001) and 10-year probability of major (15.0 [18.9] vs. 12.0 [15.3], p = 0.0461) or hip (5.0 [9.2] vs. 3.6 [8.2], p = 0.0118) fracture, but a significantly lower BMD of the FN (p = 0.0196). The rates of osteoporosis and previous fracture were comparable. There were 130, 127, 132, and 132 patients in groups I-IV, respectively. The DAS28-ESR was significantly different (p = 0.0001) among the groups and correlated to anti-CCP levels. The BMD and 10-year probability of major (p = 0.0067) and hip (p = 0.0013) fracture among the groups were also different. CONCLUSIONS: Anti-CCP+ RA patients had a higher 10-year probability of major or hip fracture, independent of anti-CCP levels, and a lower BMD of the FN than anti-CCP- patients.

Delayed anti-TNF therapy increases the risk of total knee replacement in patients with severe rheumatoid arthritis.

BACKGROUND: This study evaluated the effect of early anti-tumor necrosis factor (TNF) therapy in patients with severe rheumatoid arthritis (RA) on the subsequent risk of total knee replacement (TKR) surgery. METHODS: This retrospective observational study included a hospital-based cohort of 200 patients diagnosed with severe RA who received treatment with anti-TNF therapy between 2003 and 2014. Clinical parameters including age, sex, body mass index, and the time from the diagnosis of RA to the initiation of anti-TNF therapy were analyzed. RESULTS: Of the 200 enrolled patients, 84 underwent an early intervention (≤3 years from the diagnosis of RA to the initiation of anti-TNF therapy), and 116 underwent a late intervention(>3 years from the diagnosis of RA to the initiation of anti-TNF therapy). Five (6.0%) patients in the early intervention group underwent TKR compared to 31 (26.7%) in the late intervention group (p = 0.023). After adjusting for confounding factors, the late intervention group still had a significantly higher risk of TKR (p = 0.004; odds ratio, 5.572; 95% confidence interval, 1.933-16.062). Those receiving treatment including methotrexate had a lower risk of TKR (p = 0.004; odds ratio, 0.287; 95% confidence interval, 0.122-0.672). CONCLUSIONS: Delayed initiation of anti-TNF therapy in the treatment of severe RA was associated with an increased risk of TKR surgery. Adding methotrexate treatment decreased the risk of future TKR.

Beyond bone mineral density, FRAX-based tailor-made intervention thresholds for therapeutic decision in subjects on glucocorticoid: A nationwide osteoporosis survey.

Glucocorticoid-induced osteoporosis (GIOP) is the most common cause of secondary osteoporosis and confers a substantial risk for future fractures. Several recent guidelines for GIOP management have recommended the use of intervention thresholds to direct pharmacological therapy in those at high risk of fracture. The aim of this study was to analyze the characteristics of subjects on a glucocorticoid (GC) and to implement the Fracture Risk Assessment Tool (FRAX)-based intervention threshold for therapeutic decision-making.This was a cohort substudy of a nationwide osteoporosis screening program conducted in Taiwan from 2008 to 2011. All participants were requested to complete a questionnaire including FRAX elements, and antiosteoporosis medication (AOM) history was assessed before bone mineral density (BMD) measurement. GC users were recruited as the study group. Controls comprised randomly selected age- and sex-matched non-GC users. Individual intervention threshold (IIT) was set at individual-specific FRAX probability of a major osteoporotic fracture, relative to subjects with prior fractures. The characteristics and calculated IIT of all participants were analyzed.A total of 8704 participants were enrolled, including GC users (n = 807) and controls (n = 7897). There was no significant difference in BMD between GC users and controls. Clinical fracture risks, including previous fracture, parental hip fracture, rheumatoid arthritis, and secondary osteoporosis were higher in GC users than in controls. GC users had a higher 10-year probability of either major or hip fracture than controls. The proportion of GC users with a 10-year probability of major osteoporotic fracture above IIT was higher than in controls (75.0% vs 10.6%; P < 0.001). Only 20.3% of GC users and 30.5% of controls whose fracture risk was above IIT reported taking AOM.These findings suggest that more GC users should receive active intervention based on IIT, regardless of BMD. However, less than one-fourth of GC users whose fracture risk was above IIT received AOM, indicating that GIOP is markedly undertreated. We recommend commencing AOM for GIOP according to IIT, instead of BMD alone.

Serial plasma deoxyribonucleic acid levels as predictors of outcome in acute traumatic brain injury.

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 value >72.95 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.

Adherence to osteoporosis regimens among men and analysis of risk factors of poor compliance: a 2-year analytical review.

BACKGROUND: To investigate adherence and patient-specific factors associated with poor compliance with osteoporosis regimens among men. METHODS: In this retrospective chart review study, we collected data on male patients with osteoporosis treated in accordance with therapeutic recommendations. Adherence was determined by the compliance and persistence of those patients who had been dispensed an osteoporosis regimen after an index prescription. All osteoporosis regimens were considered equivalent for the purpose of investigating adherence. RESULTS: The prescriptions of 333 males met the inclusion criteria for data collection. The mean age was 68.6 ± 10.4 years. The median medication possession ratio (MPR, %) at years 1 and 2 was 90.1% (interquartile range (IQR) 19-100) and 53.7% (IQR 10.4-100), respectively; 52.3% of male patients at year 1 and 37.5% at year 2 had good compliance (defined as a MPR≧80%). The 1- and 2-year persistence rates were 45.9% and 30.0%, respectively. Patient-specific factors associated with poor compliance (MPR < 80%) during year 1 were first prescriptions given by orthopedists (odds ratio (OR) = 2.67; 95% confidence interval (CI) = 1.58-4.53; adjusted OR = 2.30, 95% CI = 1.26-4.22, p = 0.007). Male patients with rheumatoid arthritis (RA) (OR = 0.22, 95% CI = 0.06-0.78, adjusted OR = 0.19, 95% CI = 0.04-0.81, p = 0.025) and baseline bone mineral density (BMD) measurements (OR = 0.52, 95% CI = 0.32-0.85; adjusted OR = 0.51; 95% CI = 0.28-0.93, p = 0.029) were less likely to have poor compliance. CONCLUSIONS: Adherence to osteoporosis regimens in males was suboptimal in our study. Poor compliance was more likely in prescription of the first anti-osteoporotic regimen by an orthopedist. Men with RA and BMD measurements before therapy had a lower risk of non-adherence. Healthcare professionals need to target patients with specific factors to improve adherence to osteoporotic regimens.

Differences in adherence to osteoporosis regimens: a 2-year analysis of a population treated under specific guidelines.

BACKGROUND: Patients' adherence to antiosteoporotic drug therapy is essential to prevent fracture and complications of osteoporosis over the long term. The guidance given in treating osteoporosis can potentially enhance adherence. OBJECTIVE: This study was conducted to compare adherence to osteoporosis regimens by patients treated under specific guidelines in a medical center. METHODS: This study used a database pertaining to the use of antiosteoporotic medication, including alendronate, raloxifene, and calcitonin, between 2001 and 2007. We selected patients who were being treated following the therapeutic recommendations of the National Osteoporosis Foundation or the guideline for glucocorticoid-induced osteoporosis recommended by the American College of Rheumatology. Adherence was determined by compliance and the persistence ratio (PR). Compliance was estimated by using the medication possession rate, and PR was determined by the percentage of patients with no medication refill gap for a period of ≥30 days. RESULTS: A total of 2975 patients met the inclusion criteria. The patients were grouped according to treatment regimen: alendronate, n = 1745; raloxifene, n = 711; and calcitonin, n = 519. The good compliance rate (GCR; medication possession rate ≥80%) for alendronate, raloxifene, and calcitonin was 61.9%, 54.6%, and 36.4% at year 1 (P < 0.001), respectively. The GCR of alendronate was significantly higher than that for either raloxifene (P = 0.001) or calcitonin (P < 0.001). The GCR of the alendronate, raloxifene, and calcitonin groups at year 3 was 47.9%, 43.7%, and 36.4% of the included patients (P < 0.001). The PR of the alendronate, raloxifene, and calcitonin groups at year 1 was 57.1%, 50.2%, and 32.9% (P < 0.001) and 41.8%, 40.1%, and 23.5% (P < 0.001) at year 2. CONCLUSIONS: Alendronate had a better adherence profile than raloxifene and calcitonin at the end of year 1 and a better adherence profile than calcitonin at the end of year 2.

Serum adhesion molecules, outcome and neuro-psychological function in acute traumatic brain injury patients.

BACKGROUND: Serum concentrations of adhesion molecules may be associated with secondary brain injury after acute traumatic brain injury (TBI). METHODS: Blood samples of 68 patients admitted within 24h after TBI were obtained on admission and on Days 4 and 7 after TBI. Patients received neuro-psychological testing on discharge and at 3 months after TBI. RESULTS: Compared to controls, patients with acute TBI had markedly increased sICAM-1 and sVCAM-1 on presentation (p=0.002 and p=0.021, respectively), but markedly decreased sL-selectin and sE-selectin (p=0.009 and p≤0.001, respectively). Outcome was assessed upon discharge using the Glasgow Outcome Scale (GOS). Good outcome was defined as GOS ≥4 and poor outcome as GOS ≤3. Motor deficits on admission (p≤0.001), Glasgow Coma Scale score on admission (p=0.002), Injury Severity Score on admission (p=0.009), neuro-surgical intervention (p=0.004), post-traumatic seizure (p=0.04), and sVCAM-1 level on admission (p=0.033) were significant risk factors of outcome. A sVCAM-1 cut-off value of 752.5ng/ml on admission had 80.0% sensitivity and 68.1% specificity for predicting outcome. CONCLUSION: Serum adhesion molecules are not specific for predicting outcome in patients with TBI. However, higher mean levels of these molecules on admission may imply more severe inflammatory response causing secondary brain injury and worse neuro-psychological function. These molecules may be added as evaluation markers in clinical practice.

Bacterial brain abscess in patients with nasopharyngeal carcinoma following radiotherapy: microbiology, clinical features and therapeutic outcomes.

BACKGROUND: This study aimed to analyze the clinical features, causative pathogens, neuro-imaging findings, and therapeutic outcomes of bacterial brain abscess in patients with nasopharyngeal carcinoma (NPC) following radiotherapy. METHODS: NPC patients with bacterial brain abscess were evaluated. Their clinical data were collected over a 22-year period. For comparison, the clinical features, causative pathogens, neuro-imaging findings, and therapeutic outcomes between NPC and non-NPC patients were analyzed. RESULTS: NPC accounted for 5.7% (12/210) of the predisposing factors, with Viridans streptococci and Staphylococcus aureus as the two most common causative pathogens. Significant statistical analysis between the two groups (NPC and non-NPC patients) included chronic otitis media (COM) as the underlying disease, post-radiation necrosis by neuro-imaging, and the temporal lobe as the most common site of brain abscesses. The fatality rate in patients with and without NPC was 16.7% and 20.7%, respectively. CONCLUSIONS: NPC patients with bacterial brain abscess frequently have COM as the underlying disease. Neuro-imaging often reveals both post-radiation necrosis and the temporal lobe as the most common site of brain abscesses, the diagnosis of which is not always a straightforward process. Radiation necrosis can mimic brain abscess on neuro-imaging and pose significant diagnostic challenges. Early diagnosis and treatment is essential for survival.

Predictors and outcomes of shunt-dependent hydrocephalus in patients with aneurysmal sub-arachnoid hemorrhage.

BACKGROUND: Hydrocephalus following spontaneous aneurysmal sub-arachnoid hemorrhage (SAH) is often associated with unfavorable outcome. This study aimed to determine the potential risk factors and outcomes of shunt-dependent hydrocephalus in aneurysmal SAH patients but without hydrocephalus upon arrival at the hospital. METHODS: One hundred and sixty-eight aneurysmal SAH patients were evaluated. Using functional scores, those without hydrocephalus upon arrival at the hospital were compared to those already with hydrocephalus on admission, those who developed it during hospitalization, and those who did not develop it throughout their hospital stay. The Glasgow Coma Score, modified Fisher SAH grade, and World Federation of Neurosurgical Societies grade were determined at the emergency room. Therapeutic outcomes immediately after discharge and 18 months after were assessed using the Glasgow Outcome Score. RESULTS: Hydrocephalus accounted for 61.9% (104/168) of all episodes, including 82 with initial hydrocephalus on admission and 22 with subsequent hydrocephalus. Both the presence of intra-ventricular hemorrhage on admission and post-operative intra-cerebral hemorrhage were independently associated with shunt-dependent hydrocephalus in patients without hydrocephalus on admission. After a minimum 1.5 years of follow-up, the mean Glasgow outcome score was 3.33 ± 1.40 for patients with shunt-dependent hydrocephalus and 4.21 ± 1.19 for those without. CONCLUSIONS: The presence of intra-ventricular hemorrhage, lower mean Glasgow Coma Scale score, and higher mean scores of the modified Fisher SAH and World Federation of Neurosurgical grading on admission imply risk of shunt-dependent hydrocephalus in patients without initial hydrocephalus. These patients have worse short- and long-term outcomes and longer hospitalization.

Plasma nuclear and mitochondrial DNA levels as predictors of outcome in severe sepsis patients in the emergency room.

BACKGROUND AND AIM: The sensitivity and specificity of biomarkers and scoring systems used for predicting fatality of severe sepsis patients remain unsatisfactory. This study aimed to determine the prognostic value of circulating plasma DNA levels in severe septic patients presenting at the Emergency Department (ED). METHODS: Sixty-seven consecutive patients with severe sepsis and 33 controls were evaluated. Plasma DNA levels were estimated by real-time quantitative polymerase chain reaction assay using primers for the human ß-hemoglobin and ND2 gene. The patients' clinical and laboratory data on admission were analyzed. RESULTS: The median plasma nuclear and mitochondria DNA levels for severe septic patients on admission were significantly higher than those of the controls. The mean plasma nuclear DNA level on admission correlated with lactate concentration (γ = 0.36, p = 0.003) and plasma mitochondrial DNA on admission (γ = 0.708, p < 0.001). Significant prognostic factors for fatality included mechanical ventilation within the first 24 hours (p = 0.013), mean sequential organ failure assessment (SOFA) score on admission (p = 0.04), serum lactate (p < 0.001), and both plasma nuclear and mitochondrial DNA on admission (p < 0.001). Plasma mitochondrial DNA was an independent predictor of fatality by stepwise logistic regression such that an increase by one ng/mL in level would increase fatality rate by 0.7%. CONCLUSION: Plasma DNA has potential use for predicting outcome in septic patients arriving at the emergency room. Plasma mitochondrial DNA level on admission is a more powerful predictor than lactate concentration or SOFA scores on admission.

Gout and type 2 diabetes have a mutual inter-dependent effect on genetic risk factors and higher incidences.

OBJECTIVE: To explore the causal relationship between gout and Type 2 diabetes based on genetic evidence and national outpatient database. METHODS: Twenty male gout patients with early-onset, gout family history, without a habit of alcohol consumption or obesity before the first attack of gout were selected from hospital in 2010; and 42 unrelated male Chinese subjects were selected from HapMap as controls for genome-wide analysis study (GWAS). The comorbid diseases with gout were revealed by applying the significant single nucleotide polymorphisms (SNPs) to MetaCore platform, and the comorbid relationship was analysed by standardized incidence ratio (SIR) from outpatient database. RESULTS: A total of 334 SNPs were significantly related to gout in GWAS (P < 10(-7)), and Type 2 diabetes was the most significantly associated disease with gout as recognized by 36 gene symbols correspondent to the above significant SNPs. The analysis of national outpatient database showed that the overall incident Type 2 diabetes was 1.50 cases per 1000 person-months among gout patients, which was higher than the overall incident gout (1.06 cases) among Type 2 diabetes. The age-adjusted SIR of incident Type 2 diabetes among gout was 2.59 (95% CI 2.42, 2.78), whereas the age-adjusted SIR for incident gout among Type 2 diabetes was 1.61 (95% CI 1.48, 1.74). CONCLUSION: After excluding obesity and alcohol consumption behaviour, this study showed that patients with gout and Type 2 diabetes shared the common genetic factors most, and that there existed a mutual inter-dependent effect on higher incidences.

Ischemia heart disease and greater waist circumference are risk factors of renal function deterioration in male gout patients.

We examined the incidence of renal function deterioration (RFD) in a population of male gout patients and to identify associated risk factors. Subjects who had been regularly followed up for more than 2 years and had visited Chang Gung Memorial Hospital-Kaohsiung Medical Center Rheumatology Clinic between June 1, 2006 and January 31, 2007 were enrolled. Four subjects were excluded as secondary gout was suspected. Group I (Gr I) comprised subjects without RFD and group II (Gr II) comprised subjects with RFD during the follow-up period. RFD was defined as absolute increment in creatinine (Cr) levels over 0.4 mg/dl for subjects with baseline Cr levels 1.4 mg/dl. Clinical parameters were analyzed to study the potential risk factors of RFD. Of 318 male gout patients, 296 (93.1%) were categorized as Gr I, and 22 (6.9%) were categorized as Gr II. The observation periods for Gr I and Gr II were 81.20+/-53.29 and 92.41+/-46.72 months, respectively (p=0.338). Initial Cr levels are similar between the two groups (1.25+/-0.51 vs 1.25+/-0.61, p=0.963). Multiple logistic regression analysis revealed that current age, age at disease onset, disease duration, treatment duration, body weight, height, family history of gout, tophi, urolithiasis, tobacco use, alcohol consumption, history of cerebral vascular accident, hypertension, diabetes mellitus, dyslipidemia, base-line and final Cr, blood urea nitrogen level, serum uric acid level, and body-mass index were not independent risk factors. However, history of ischemic heart disease [IHD; odds ratio (OR) 7.68, 95% confidence interval (CI) 1.99-29.70] and greater waist circumference (WC; OR 1.06, 95% CI 1.01-1.11) were two independent risk factors of RFD. Additionally, the Cox multivariable analysis disclosed that IHD (p<0.001) and greater WC (p=0.011) deteriorated kidney function in these patients. The incidence of RFD in male gout patients is 6.9%. History of IHD and greater WC are two independent risk factors for developing RFD.

Incidental discovery of high systemic lupus erythematosus disease activity associated with cytomegalovirus viral activity.

We try to find the association of cytomegalovirus (CMV) infection and anti-beta2 glycoprotein 1 autoantibodies (anti-beta2 GP1), a key antibody in antiphospholipid syndrome (APS), among systemic lupus erythematosus (SLE) and cerebral vascular accident (CVA) patients. This retrospective study enrolled serum samples obtained from 87 SLE and 97 CVA patients who have been checked for the existence of anti-beta2 GP1. First, the prevalence rate of anti-CMV IgG and IgM in patients with and without anti-beta2 GP1 were compared. Second, the prevalence of anti-CMV IgG and IgM were compared between SLE and CVA patients. Last, this study analyzed the clinical characteristics and disease activity in SLE patients with positive anti-CMV IgM and IgG. No difference existed in the prevalence rate of anti-CMV IgG and IgM between positive or negative anti-beta2 GP1 serum samples in both SLE and CVA patients. However, the prevalence of anti-CMV IgM was significantly higher in the SLE group than in the CVA group. Severity of clinical features and SLEDAI scores were considerably higher in patients with positive anti-CMV IgM than in SLE patients with negative anti-CMV IgM. Very impressively, all IgM-positive SLE samples (9/9) carrying highest levels of anti-CMV IgG, indicated reactivation of the latent CMV infection. Hence, it suggests that CMV reactivation might contribute toward the disease flare in some SLE patients. In future, a prospective and longitudinal study is stongly indicated.