Cervical spinal manipulation is considered to be a safe procedure for treating patients with neck pain and muscle-tension headache. Rarely has acute cervical spinal epidural hematoma after spinal manipulation been reported. Here, we report a 16-year-old healthy male adolescent who presented with progressive weakness in the right extremities following acute neck and shoulder pain after spinal manipulation from Acute cervical spinal epidural hematoma with compression of spinal cord. After emergency surgery the patient had full recovery from the profound neurological deficits.
Hematoma, Epidural, Spinal

BACKGROUNDEstrogen deficiency results in loss of bone mass. Phytoestrogens are plant-derived non-steroidal compounds with estrogen-like activity that bind to estrogen receptors. The main aim of this study was to investigate the effect of the phytoestrogen puerarin on adult mouse osteoblasts.

METHODSOsteoblast cells were harvested from 8-month old female imprinting control region (ICR) mice. The effects of puerarin stimulation on the proliferation, differentiation and maturation of osteoblasts were examined. The production of nitric oxide (NO) and the expression of bone morphogenetic protein-2 (BMP-2), SMAD4, mitogen-activated protein kinases (MAPK), core binding factor α1/ runt-related transcription factor 2 (Cbfa1/Runx2), osteoprotegerin (OPG), and receptor activator of NF-κB ligand (RANKL) genes were analyzed. The activation of signal pathways was further confirmed by specific pathway inhibitors.

RESULTSThe osteoblast viability reached its maximum at 10(-8) mol/L puerarin. At this concentration, puerarin increases the proliferation and matrix mineralization of osteoblasts and promotes NO synthesis. With 10(-8) mol/L puerarin treatment, BMP-2, SMAD4, Cbfa1/Runx2, and OPG gene expression were up-regulated, while the RANKL gene expression is down-regulated. Concurrent treatment involving the (bone morphogenetic protein) BMP antagonist Noggin or the NOS inhibitor L-NAME diminishes puerarin induced cell proliferation, Alkaline phosphatase (ALP) activity, NO production, as well as the BMP-2, SMAD4, Cbfa1/Runx2, OPG, and RANKL gene expression.

CONCLUSIONSIn this in vitro study, we demonstrate that puerarin is a bone anabolic agent that exerts its osteogenic effects through the induction of BMP-2 and NO synthesis, subsequently regulating Cbfa1/Runx2, OPG, and RANKL gene expression. This effect may contribute to its induction of osteoblast proliferation and differentiation, resulting in bone formation.

Animals ; Bone Morphogenetic Protein 2 ; genetics ; physiology ; Cell Differentiation ; drug effects ; Cell Survival ; drug effects ; Cells, Cultured ; Female ; Isoflavones ; pharmacology ; MAP Kinase Signaling System ; physiology ; Mice ; Mice, Inbred ICR ; Nitric Oxide ; physiology ; Osteoblasts ; drug effects ; metabolism ; Osteogenesis ; drug effects ; Phytoestrogens ; pharmacology ; RANK Ligand ; genetics

Objective: The purpose of this study is to investigate the safety, tolerability and efficacy of titrating dose of rivastigmine oral solution in patients with mild to moderate Alzheimer’s disease (AD) in Taiwan. Methods: We recruited 108 mild to moderate AD patients with RivastⓇ (rivastigmine oral solution 2 mg/ml) treatment for 52 weeks. We recorded the demographic characteristics, initial cognition by mini-mental state examination (MMSE), initial global status by clinical dementia rating (CDR) with CDR-Sum of Boxes (CDR-SB), initial dose, and titrating dose at each visit. We investigated the adherence, proportion of possible side effects, optimal dose, and time to optimal dose. We demonstrated the proportion of cognitive decline and its possible risk factors. Results: During the course, 9 patients discontinued the rivastigmine oral solution due to poor compliance or preference. Twelve out of 99 patients (12.1%) reported possible side effects. Among 87 patients, the mean age was 77.2 ± 9.0 years ago with female predominant (65.2%). The optimal dose was 3.6 ± 1.4 ml in average and 4 ml (n = 31, 35.6%) in mode. The duration to optimal dose was 12.5 ± 10.2 weeks and 24 weeks (n = 35, 40.2%) in mode. It presented 25% with cognitive decline in MMSE, 27% with global function decline in CDR and 63% with global function decline in CDR-SB. Conclusion We demonstrated the clinical experience of rivastigmine oral solution in mild to moderate AD patients. It suggested rivastigmine oral solution 4ml is the optimal dose with 24 weeks to the optimal dose for at least one third of patients.

Objective: The purpose of this study is to investigate the safety, tolerability and efficacy of titrating dose of rivastigmine oral solution in patients with mild to moderate Alzheimer’s disease (AD) in Taiwan. Methods: We recruited 108 mild to moderate AD patients with RivastⓇ (rivastigmine oral solution 2 mg/ml) treatment for 52 weeks. We recorded the demographic characteristics, initial cognition by mini-mental state examination (MMSE), initial global status by clinical dementia rating (CDR) with CDR-Sum of Boxes (CDR-SB), initial dose, and titrating dose at each visit. We investigated the adherence, proportion of possible side effects, optimal dose, and time to optimal dose. We demonstrated the proportion of cognitive decline and its possible risk factors. Results: During the course, 9 patients discontinued the rivastigmine oral solution due to poor compliance or preference. Twelve out of 99 patients (12.1%) reported possible side effects. Among 87 patients, the mean age was 77.2 ± 9.0 years ago with female predominant (65.2%). The optimal dose was 3.6 ± 1.4 ml in average and 4 ml (n = 31, 35.6%) in mode. The duration to optimal dose was 12.5 ± 10.2 weeks and 24 weeks (n = 35, 40.2%) in mode. It presented 25% with cognitive decline in MMSE, 27% with global function decline in CDR and 63% with global function decline in CDR-SB. Conclusion We demonstrated the clinical experience of rivastigmine oral solution in mild to moderate AD patients. It suggested rivastigmine oral solution 4ml is the optimal dose with 24 weeks to the optimal dose for at least one third of patients.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.