Discovering Hair Biomarkers of Alzheimer's Disease Using High Resolution Mass Spectrometry-Based Untargeted Metabolomics.

Hair may be a potential biospecimen to discover biomarkers for Alzheimer's disease (AD) since it reflects the integral metabolic profiles of body burden over several months. Here, we described the AD biomarker discovery in the hair using a high-resolution mass spectrometry (HRMS)-based untargeted metabolomics approach. A total of 24 patients with AD and 24 age- and sex-matched cognitively healthy controls were recruited. The hair samples were collected 0.1-cm away from the scalp and further cut into 3-cm segments. Hair metabolites were extracted by ultrasonication with methanol/phosphate-buffered saline 50/50 (v/v) for 4 h. A total of 25 discriminatory chemicals in hair between the patients with AD and controls were discovered and identified. The AUC value achieved 0.85 (95% CI: 0.72~0.97) in patients with very mild AD compared to healthy controls using a composite panel of the 9 biomarker candidates, indicating high potential for the initiation or promotion phase of AD dementia in the early stage. A metabolic panel combined with the nine metabolites may be used as biomarkers for the early detection of AD. The hair metabolome can be used to reveal metabolic perturbations for biomarker discovery. Investigating perturbations of the metabolites will offer insight into the pathogenesis of AD.

A study of correlations between metabolic syndrome factors and osteosarcopenic adiposity.

BACKGROUND: Aging reduces the quality and strength of bones and muscles and increases body fat, which can lead to the simultaneous occurrence of sarcopenia, osteopenia, and adiposity, a condition referred to as OsteoSarcopenic Adiposity (OSA). While previous studies have demonstrated that metabolic syndrome is associated with sarcopenia, osteopenia, and adiposity, the relationship between metabolic syndrome and OSA remains largely unknown. METHODS: We analyzed data for a sample of middle-aged individuals from a Health Management Center database, which was collected in 2016-2018. There are 2991 cases of people over 50 years from a physical examination center in a hospital in Taiwan during 2016-2018. In addition to descriptive statistics, chi-squared test, analysis of variance, and multinomial logistic regression analysis were conducted to examine OSA risk and associated factors. RESULTS: Based on multinomial logistic regression analysis, in different OSA severity level (1-3 more serious), those who are with metabolic syndrome has increased the 2.49-2.57 times risk of OSA (p < 0.001) in OSA = 2 and 3 groups while there is no significant difference in OSA =1 group. CONCLUSION: The prevalence of OSA may impair the health and quality of life in the elderly group, especially those diagnosed with metabolic syndrome, increasing the risk of OSA. These results can help promote early diagnosis and treatment of OSA in clinical settings, particularly among aging individuals with abnormal physical function, the group with the highest OSA incidence.

Safety and Effectiveness of Intravenous Thrombolysis for Acute Ischemic Stroke Outside the Coverage of National Health Insurance in Taiwan.

PURPOSE: Only a small percentage of ischemic stroke patients were treated with intravenous thrombolysis in Taiwan, partly because of the narrow reimbursement criteria of the National Health Insurance (NHI). We aimed to assess the safety and effectiveness of intravenous thrombolysis not covered by the NHI. METHODS: This is a retrospective analysis of register data from four hospitals. All patients who received intravenous tissue plasminogen activator and fulfilled the American Heart Association/American Stroke Association (AHA/ASA) thrombolysis guidelines between January 2007 and June 2012 were distinguished into two groups: those in accordance (reimbursement group) and those not in accordance (non-reimbursement group) with the NHI reimbursement criteria. Primary outcome was symptomatic intracerebral hemorrhage (SICH). Secondary outcomes were dramatic improvement in the National Institutes of Health Stroke Scale (NIHSS) score at discharge, good functional outcome (modified Rankin Scale ≤2) at discharge, and all-cause in-hospital mortality. RESULTS: In 569 guideline-eligible patients, 177 (31%) were treated without reimbursement. The reasons for exclusion from reimbursement included age >80 (n=42), baseline NIHSS less than 6 (n=29), baseline NIHSS >25 (n=15), thrombolysis beyond 3 hours (n=49), prior stroke with diabetes (n=28), use of oral anticoagulant (n=2), and more than one contraindication (n=12). Overall, we observed no differences between the reimbursement and non-reimbursement groups in the rate of SICH (7% versus 6%), dramatic improvement (36% versus 36%), good functional outcome (39% versus 37%), and in-hospital mortality (8% versus 6%) Conclusion: In stroke patients treated with intravenous thrombolysis according to the AHA/ASA guidelines, the outcomes were comparable between the reimbursement and non-reimbursement groups.

Massive Spontaneous Symptomatic Hemorrhagic Transformation Following Pontine Infarction - A Case Report.

PURPOSE: Spontaneous hemorrhagic transformation is common in anterior circulation infarction, but is rarely seen in brainstem infarction. We report a case of massive symptomatic brainstem hemorrhagic transformation in a patient with pontine infarction treated with only antiplatelet agents. CASE REPORT: A 59-year-old man presented with acute dysarthria and right sided weakness. His Glasgow coma scale was E3 V5 M6. His pupils were pinpoint in size and minimally reactive to light. He showed complete horizontal gaze palsy, right facial weakness, severe dysarthria, dysphagia, and right hemiplegia. Computed tomography showed a dense basilar artery sign without evidence of acute infarction or hemorrhage. After treated with aspirin and dipyridamole, he had massive symptomatic brainstem hemorrhagic transformation on the next day. After medical treatment, he survived but remained in locked-in state with occasional drowsiness. CONCLUSION: Hemorrhagic transformation following brainstem infarction is a rare yet potentially devastating condition in patients without thrombolytic therapy. It should be considered when neurological deterioration develops in patients with brainstem infarction. Follow-up brain imaging studies are warranted because antithrombotic agents should be discontinued in case of hemorrhagic transformation.

Clinical Profile and Outcome of Myasthenic Crisis In Central Taiwan.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease caused by antibodies to acetylcholine receptors of the skeletal muscle. Myasthenic crisis (MC) is a complication observed during both early and late stage MG cases. In this study, we examined current treatments and three years outcomes in patients with MG and MC. We also investigated the impact of thymectomy and systemic lupus erythematosus (SLE) in patients with MG and MC. METHODS: In this retrospective study, we reviewed the medical records of all patients admitted to one teaching hospital between January 2006 and December 2014 and identified those for whom discharge diagnosis included the International Classification of Diseases, ninth revision (ICD-9) codes corresponding to MG (358.X, all extensions and all positions). RESULTS: We identified 29 patients and 49 hospitalizations. Among these patients, the cause for initial hospitalization was MG in 16 cases and MC in 13 cases. Six out of the 16 MG patients were readmitted within 3 years; with 2 of the cases due to MC. Eight of the initial 13 MC patients were readmitted within 3 years, and 6 of the cases due to MC. Among these 15 MC patients, 14 were admitted to the intensive care unit (ICU), and 8 were intubation and put on mechanical ventilators. The median ICU stay was 7 days (3-45). Both MG patients who were also diagnosed with SLE experienced MC. One patient died during the first-time hospitalization, and one patient died during re-hospitalization within 2 years. CONCLUSION: Plasma exchange (PE) is the main treatment modality of MC, and most patients in our cohort had a good response. Infection is the most common trigger of MC and a significant cause of death. Despite significant morbidity and mortality in patients with MC, a favorable long-term outcome is possible with intensive treatment. Key Words: myathenia gravis, myasthenic crisis, systemic lupus erythematosus, outcome.

Underestimated Rate of Status Epilepticus according to the Traditional Definition of Status Epilepticus.

PURPOSE: Status epilepticus (SE) is an important neurological emergency. Early diagnosis could improve outcomes. Traditionally, SE is defined as seizures lasting at least 30 min or repeated seizures over 30 min without recovery of consciousness. Some specialists argued that the duration of seizures qualifying as SE should be shorter and the operational definition of SE was suggested. It is unclear whether physicians follow the operational definition. The objective of this study was to investigate whether the incidence of SE was underestimated and to investigate the underestimate rate. METHODS: This retrospective study evaluates the difference in diagnosis of SE between operational definition and traditional definition of status epilepticus. Between July 1, 2012, and June 30, 2014, patients discharged with ICD-9 codes for epilepsy (345.X) in Chia-Yi Christian Hospital were included in the study. A seizure lasting at least 30 min or repeated seizures over 30 min without recovery of consciousness were considered SE according to the traditional definition of SE (TDSE). A seizure lasting between 5 and 30 min was considered SE according to the operational definition of SE (ODSE); it was defined as underestimated status epilepticus (UESE). RESULTS: During a 2-year period, there were 256 episodes of seizures requiring hospital admission. Among the 256 episodes, 99 episodes lasted longer than 5 min, out of which 61 (61.6%) episodes persisted over 30 min (TDSE) and 38 (38.4%) episodes continued between 5 and 30 min (UESE). In the 38 episodes of seizure lasting 5 to 30 minutes, only one episode was previously discharged as SE (ICD-9-CM 345.3). Conclusion. We underestimated 37.4% of SE. Continuing education regarding the diagnosis and treatment of epilepsy is important for physicians.

Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan.

BACKGROUND: Carbamazepine, an anticonvulsant and a mood-stabilizing drug, is the main cause of the Stevens-Johnson syndrome (SJS) and its related disease, toxic epidermal necrolysis (TEN), in Southeast Asian countries. Carbamazepine-induced SJS-TEN is strongly associated with the HLA-B*1502 allele. We sought to prevent carbamazepine-induced SJS-TEN by using HLA-B*1502 screening to prospectively identify subjects at genetic risk for the condition. METHODS: From 23 hospitals in Taiwan, we recruited 4877 candidate subjects who had not taken carbamazepine. We genotyped DNA purified from the subjects' peripheral blood to determine whether they carried the HLA-B*1502 allele. Those testing positive for HLA-B*1502 (7.7% of the total) were advised not to take carbamazepine and were given an alternative medication or advised to continue taking their prestudy medication; those testing negative (92.3%) were advised to take carbamazepine. We interviewed the subjects by telephone once a week for 2 months to monitor them for symptoms. We used the estimated historical incidence of SJS-TEN as a control. RESULTS: Mild, transient rash developed in 4.3% of subjects; more widespread rash developed in 0.1% of subjects, who were hospitalized. SJS-TEN did not develop in any of the HLA-B*1502-negative subjects receiving carbamazepine. In contrast, the estimated historical incidence of carbamazepine-induced SJS-TEN (0.23%) would translate into approximately 10 cases among study subjects (P<0.001). CONCLUSIONS: The identification of subjects carrying the HLA-B*1502 allele and the avoidance of carbamazepine therapy in these subjects was strongly associated with a decrease in the incidence of carbamazepine-induced SJS-TEN. (Funded by the National Science Council of Taiwan and the Taiwan Drug Relief Foundation.).

Association Between Abnormal Course of Carotid Artery and Cerebrovascular Disease.

PURPOSE: Abnormal course of the carotid artery (ABCA) is commonly identified during carotid sonography studies. Whether ABCA is related to the risk of stroke and stroke risk factors remains unclear. The purpose of the study is to investigate the prevalence of ABCA and the relationship with stroke and the risk factors of stroke. METHODS: Color duplex ultrasound scanning of carotid arteries was performed on 615 subjects (between January 1, 2012 and March 31, 2012). ABCA and intimal thickness were recorded. Risk factors of stroke such as hypertension, diabetes mellitus, dyslipidemia, atherosclerosis, stroke history, and heart disease were recorded. The prevalence of ABCA was analyzed and its relationship with stroke and stroke risk factors was evaluated. RESULTS: ABCA was found in 4.1% (25/615) patients, 6.29% (19/302) in women, and 1.91% (6/313) in men. ABCA in 1 vessel was noted in 18 patients, 2 vessels in 3 patients, 3 vessels in 3 patients, and 4 vessels in 1 patient. The frequency of ABCA was significantly higher in women than in men (6.3% vs 1.9%, p = 0.01). There was no difference in the prevalence of ABCA between stroke patients and nonstroke subjects ( p = 0.60). ABCA was more frequent in patients older than 65 years. (5.91% (22/372) vs. 1.23% (3/243) p = 0.01). Logistic regression analysis did not reveal associations between ABCA and stroke risk factors (hypertension, diabetes mellitus, dyslipidemia, stroke history, heart disease and atherosclerosis). During 1 year follow-up, 2.88% (17/590) of non-ABCA patients and 4.0% (1/25) of ABCA patients had event of stroke or transient ischemic attack (TIA) ( p =0.08). CONCLUSION: The prevalence of ABCA in the present study is significantly lower than that in previous studies (Togay-Isikay et al., 24.6%, Del Corso et al., 58%). ABCA is more frequent in women and older patients. ABCA is not related to stroke and stroke risk factors. From our results, we suggest that patients with ABCA be placed under observation unless they exhibit neurological symptoms.

Effects of Adding Extracorporeal Shockwave Therapy (ESWT) to Platelet-Rich Plasma (PRP) among Patients with Rotator Cuff Partial Tear: A Prospective Randomized Comparative Study.

A rotator cuff tear is a prevalent ailment affecting the shoulder joint. The clinical efficacy of combined therapy remains uncertain for partial rotator cuff tears. In this study, we integrated extracorporeal shockwave therapy (ESWT) with platelet-rich plasma (PRP) injection, juxtaposed with PRP in isolation. Both cohorts exhibited significant improvements in visual analogue scale (VAS), Constant-Murley score (CMS), degrees of forward flexion, abduction, internal rotation, and external rotation, and the sum of range of motion (SROM) over the six-month assessment period. The application of ESWT in conjunction with PRP exhibited notable additional enhancements in both forward flexion (p = 0.033) and abduction (p = 0.015) after one month. Furthermore, a substantial augmentation in the range of shoulder motion (SROM) (p < 0.001) was observed after six months. We employed isobaric tag for relative and absolute quantitation (iTRAQ) to analyze the differential plasma protein expression in serum samples procured from the two groups after one month. The concentrations of S100A8 (p = 0.042) and S100A9 (p = 0.034), known to modulate local inflammation, were both lower in the ESWT + PRP cohort. These findings not only underscore the advantages of combined therapy but also illuminate the associated molecular changes.

Monitoring long-term chemical exposome by characterizing the hair metabolome using a high-resolution mass spectrometry-based suspect screening approach.

Hair has recently emerged as a biospecimen for characterizing the long-term chemical exposome in biomonitoring investigations spanning several months, as chemical compounds circulating in the bloodstream accumulate in hair. Although there has been interest in using human hair as a biospecimen for exposome studies, it has yet to be widely adopted compared to blood and urine. Here, we applied a high-resolution mass spectrometry (HRMS)-based suspect screening strategy to characterize the long-term chemical exposome in human hair. Hair samples were collected from 70 subjects and cut into 3 cm segments, which were then mixed to prepare pooled samples. The pooled hair samples underwent a sample preparation procedure, and the hair extracts were further analyzed using an HRMS-based suspect screening approach. An in-house chemical suspect list containing 1227 chemical entries from National Report on Human Exposure to Environmental Chemicals (Report) published by the U.S. CDC and the Exposome-Explorer 3.0 database developed by the WHO was subsequently used to screen and filter the suspect features against the HRMS dataset. Overall, we matched 587 suspect features in the HRMS dataset to 246 unique chemical formulas in the suspect list, and the structures of 167 chemicals were further identified through a fragmentation analysis. Among these, chemicals such as mono-2-ethylhexyl phthalate, methyl paraben, and 1-naphthol, which have been detected in the urine or blood for exposure assessment, were also identified in human hair. This suggests that hair reflects the accumulation of environmental compounds to which an individual is exposed. Exposure to exogenous chemicals may exert adverse effects on cognitive function, and we discovered 15 chemicals in human hair that may contribute to the pathogenesis of Alzheimer's disease. This finding suggests that human hair may be a promising biospecimen for monitoring long-term exposure to multiple environmental chemicals and perturbations in endogenous chemicals in biomonitoring investigations.

Increased use of thrombolytic therapy and shortening of in-hospital delays following acute ischemic stroke: experience on the establishment of a primary stroke center at a community hospital.

PURPOSE: To improve and standardize stroke care, the establishment of primary stroke centers (PSCs) has been advised. Thrombolytic therapy has been proved to improve the outcome of acute ischemic stroke (AIS). We assessed the use of thrombolytic therapy before and after setting up a PSC at a community hospital. METHODS: In November 2007, a PSC was established at our hospital. Following guidelines based on national recommendations, we administered intravenous tissue plasminogen activator (tPA) to patients who met the criteria. To study the effects of the establishment of the PSC on tPA treatment rates, we examined our database of stroke patients dating back to January 2004. RESULTS: Before the establishment of the PSC, there have been 2,420 patients admitted to our hospital diagnosed with AIS. Only 1.2% of these patients were treated with intravenous tPA. Following the establishment of the PSC, 2.8% of 1151 AIS patients were treated with tPA. Time of patient arrival to patient treatment was also diminished. CONCLUSION: The establishment of the PSC significantly increases the usage of tPA treatment. Furthermore, response time to patient cases was also quicker. However, for maximum effectiveness, the public still needs to be made more aware of the risks of stroke and the importance of seeking medical care at the first signs of stroke.

The Impact of Loading Dose on Outcome in Stroke Patients Receiving Low-Dose Tissue Plasminogen Activator Thrombolytic Therapy.

BACKGROUND: Intravenous tissue plasminogen activator (tPA) (0.9 mg/kg, maximum 90 mg) with a bolus of 10% of the total dose given within 1-2 mins is the standard therapy for patients receiving thrombolytic therapy. Low-dose (0.6 mg/kg) tPA is also approved for thrombolytic therapy for ischemic stroke patients. Low-dose tPA is associated with a low bolus dose. It is unknown whether increasing the bolus dose in patients receiving low-dose tPA thrombolysis may improve outcomes or increase the risk of hemorrhagic transformation (HT). AIM: This study investigated the impact of the bolus dose on the outcome in ischemic stroke patients receiving low-dose tPA thrombolytic therapy. METHODS: In this retrospective, observational study, we enrolled 214 ischemic stroke patients receiving low-dose tPA thrombolytic therapy. Of these 214 patients, 107 patients received 10% of the total dose as a bolus dose, and 107 patients received 15% of the total dose as a bolus dose. The National Institutes of Health Stroke Score (NIHSS) were evaluated before tPA infusion, 24 h after thrombolytic therapy, and at discharge. Stroke severity was categorized as mild (0-5), moderate (6-14), severe (15-24), or very severe (≥25). Neurological improvement (NI) was defined as an improvement of 6 or more points in the NIHSS, and no response (NR) was defined as an increase in the NIHSS of ≤4 points or a decrease ≤6 points. Neurological deterioration (ND) was defined as an increase in the NIHSS >4 points. A good outcome was defined as a modified Ranking Score (mRS) of 0 or 1. We compared the NI, NR, and ND rates at 24 hrs after thrombolytic therapy and discharge between the 15% and 10% bolus dose groups. RESULTS: In patients with mild and moderate stroke, there was no significant difference in the NI, NR, ND, and HT rates and 6-month outcomes between the 15% and 10% bolus groups. In patients with severe and very severe stroke, outcomes at 6 months were significantly better in the 15% bolus group than in the 10% bolus group. The factors affecting the outcomes of severe and very severe stroke patients are hypertension and bolus dose. CONCLUSION: In severe and very severe stroke patients receiving low-dose tPA thrombolytic therapy, a bolus dose of 15% of the total dose can improve outcomes.

Slide-free clinical imaging of melanin with absolute quantities using label-free third-harmonic-generation enhancement-ratio microscopy.

The capability to image the 3D distribution of melanin in human skin in vivo with absolute quantities and microscopic details will not only enable noninvasive histopathological diagnosis of melanin-related cutaneous disorders, but also make long term treatment assessment possible. In this paper, we demonstrate clinical in vivo imaging of the melanin distribution in human skin with absolute quantities on mass density and with microscopic details by using label-free third-harmonic-generation (THG) enhancement-ratio microscopy. As the dominant absorber in skin, melanin provides the strongest THG nonlinearity in human skin due to resonance enhancement. We show that the THG-enhancement-ratio (erTHG) parameter can be calibrated in vivo and can indicate the melanin mass density. With an unprecedented clinical imaging resolution, our study revealed erTHG-microscopy's unique capability for long-term treatment assessment and direct clinical observation of melanin's micro-distribution to shed light into the unknown pathway and regulation mechanism of melanosome transfer and translocation.

Impact of silent infarction on the outcome of stroke patients.

BACKGROUND/PURPOSE: Silent infarcts (SIs) are commonly found on brain computed tomography (CT) or magnetic resonance imaging (MRI) among elderly subjects, but their risk factors and impact on outcome in stroke patients are unknown. We evaluated the prevalence, risk factors and impact of SIs on the outcome of patients admitted with first-ever ischemic stroke or transient ischemic attack (TIA). METHODS: A prospective study of 446 patients admitted consecutively to the neurology service with a diagnosis of TIA or stroke between July 2003 and June 2005, including 226 without any history of prior TIA or stroke. All patients underwent brain CT on the day of admission to the hospital. Risk factors analyzed included age, history of hypertension, diabetes mellitus, cardiovascular disease or stroke, smoking habit and alcohol use. Cholesterol and triglyceride levels were measured on the second day of admission. We monitored these patients for 24 months after stroke onset. RESULTS: The frequency of SIs among the 226 patients with first-ever stroke or TIA was 20%. Most of the SIs were small and deep. Small-artery disease was more frequently observed in patients with SIs. Age, hypertension, diabetes mellitus, hypercholesterolemia, hypertriglyceridemia, alcohol use, smoking habits and atrial fibrillation did not significantly differ between patients with SIs and those without SIs. During the 24-month follow-up period, the frequency of recurrent stroke was higher in patients with SIs than those without SIs. The mortality rate was higher in patients without SIs than those with SIs. The interval from stroke onset to rehospitalization was shorter in patients without SIs than in those with SIs. CONCLUSION: The study showed a higher frequency of small artery disease in patients with SIs. First-ever stroke patients with SIs should be considered at high risk for recurrent stroke.

Intravenous thrombolytic therapy for acute ischemic stroke: the experience of a community hospital.

BACKGROUND AND PURPOSE: Tissue plasminogen activator (tPA) is a standard therapy for acute ischemic stroke (AIS) but only limited data are noted in Taiwan. The purpose of this study was to assess the safety, feasibility, and efficacy of treatment in a community hospital setting. METHODS: We retrospectively reviewed the medical records of all patients who had received intravenous tPA therapy from 1998 to 2007 in our hospital. We compared the characteristics, complications, and outcomes in our patients with those of patients in the National Institute of Neurological Disorders and Stroke (NINDS) trial. RESULTS: A total of 43 patients were reviewed with a mean age of 63 years and a male predominance (64%). The median pretreatment National Institutes of Health Stroke Scale score was 18. In our patients, cardioembolism was the leading course of the strokes. The mean time from stroke onset to treatment was 134 minutes, and the mean door-to-computed tomography-time was 34 minutes while the mean door-to-needle time was 93 minutes. Within 36 hours symptomatic intracerebral hemorrhage occurred in two patients (4.7%). Four patients (9.3%) developed brain herniation with fatality. At follow-up, fourteen patients (33%) had a favorable outcome on the modified Rankin Scale (0-1). Patient outcome was not significantly different from that in the NINDS trial. CONCLUSION: Although the number of patients with AIS receiving tPA in this study was small, thrombolytic therapy can be performed safely and effectively by physicians in the community hospital setting.

Ethic issue in ischemic stroke patients wit thrombolytic therapy.

OBJECTIVE: To discuss the ethical challenge in thrombolytic therapy. BACKGROUND: Thrombolytic therapy with recombinant tissue-type plasminogen activator (rt-Pa) has been found to be beneficial to the outcome of patients who had a stroke. However, the ethic issue that is related to intravenous rt-Pa infusion has not been discussed. PATIENTS: Four patients with a middle cerebral artery (MCA) infarct arrived at the emergency department (ER) of our hospital within 3 hours of stroke onset. All of them violated the guidelines of thrombolytic therapy for patients. The families of three patients insisted on the thrombolytic therapy. Two patients received rt-Pa infusion and two did not. RESULTS: Two patients who received rt-Pa infusion experienced hemorrhagic transformation. One died on the fifth day after stroke, and the other one had a poor outcome with a modified ranking scale (mRS) of 5. One of the two patients who did not receive rt-Pa infusion suffered from hemorrhagic transformation and died on the third day after stroke, and the other one had a poor outcome with mRS of 5. CONCLUSIONS: These 4 cases highlight the complexity of thrombolytic therapy in patients who violate the guidelines because the families insisted on thrombolytic therapy. No one is sure that the family's decision was the patient's wish. When a stroke patient violates the guidelines of thrombolytic therapy and the family of the patient insists on the thrombolytic therapy, a conversation between patients, patients' families and clinicians is necessary. Physician should tell patient and their families about the high risk of hemorrhagic transformation and mortality. If the family wants to make a decision, physician should request patient or patient's families to sign an against medical advice form and follow the patient's or their family's decision for the outcome.

In vivo third-harmonic generation microscopy study on vitiligo patients.

Melanin is known to provide strong third-harmonic generation (THG) contrast in human skin. With a high concentration in basal cell cytoplasm, THG contrast provided by melanin overshadows other THG sources in human skin studies. For better understanding of the THG signals in keratinocytes without the influence of melanin, an in vivo THG microscopy (THGM) study was first conducted on vitiliginous skin. As a result, the THG-brightness ratio between the melanin-lacking cytoplasm of basal cells and collagen fibers is about 1.106 at the dermal-epidermal junctions of vitiliginous skin, indicating high sensitivity of THGM for the presence of melanin. We further applied the in vivo THGM to assist evaluating the therapeutic outcome from the histopathological point of view for those showed no improvement under narrowband ultraviolet B therapy based on the seven-point Physician Global Assessment score. Our clinical study indicates the high potential of THGM to assist the histopathological assessment of the therapeutic efficacy of vitiligo treatments.

Applying natural language processing techniques to develop a task-specific EMR interface for timely stroke thrombolysis: A feasibility study.

OBJECTIVE: To reduce errors in determining eligibility for intravenous thrombolytic therapy (IVT) in stroke patients through use of an enhanced task-specific electronic medical record (EMR) interface powered by natural language processing (NLP) techniques. MATERIALS AND METHODS: The information processing algorithm utilized MetaMap to extract medical concepts from IVT eligibility criteria and expanded the concepts using the Unified Medical Language System Metathesaurus. Concepts identified from clinical notes by MetaMap were compared to those from IVT eligibility criteria. The task-specific EMR interface displays IVT-relevant information by highlighting phrases that contain matched concepts. Clinical usability was assessed with clinicians staffing the acute stroke team by comparing user performance while using the task-specific and the current EMR interfaces. RESULTS: The algorithm identified IVT-relevant concepts with micro-averaged precisions, recalls, and F1 measures of 0.998, 0.812, and 0.895 at the phrase level and of 1, 0.972, and 0.986 at the document level. Users using the task-specific interface achieved a higher accuracy score than those using the current interface (91% versus 80%, p = 0.016) in assessing the IVT eligibility criteria. The completion time between the interfaces was statistically similar (2.46 min versus 1.70 min, p = 0.754). DISCUSSION: Although the information processing algorithm had room for improvement, the task-specific EMR interface significantly reduced errors in assessing IVT eligibility criteria. CONCLUSION: The study findings provide evidence to support an NLP enhanced EMR system to facilitate IVT decision-making by presenting meaningful and timely information to clinicians, thereby offering a new avenue for improvements in acute stroke care.

Progression of Mild to Moderate Stenosis in the Internal Carotid Arteries of Patients With Ischemic Stroke.

Background and purpose: Severe stenosis in the internal carotid artery may increase the risk of ischemic stroke. The factors that affect the progression of carotid artery stenosis in patients with ischemic stroke are poorly studied. No guidelines for the duration of follow-up of patients with ischemic stroke through carotid ultrasonography exist. Methods: In this retrospective study, 179 patients (108 men; mean age, 68 years) with ischemic stroke and mild to moderate stenosis in the internal carotid artery (ICA) were recruited. Carotid artery ultrasonography was performed over the period of January 2013 to June 2016 with a median follow-up of 36 months (mean 36.5 ± 3.5 months). The severity of carotid artery stenosis was estimated with the following equation: 1- (narrowest ICA diameter/total lumen diameter at the narrowest site). The severity of stenosis was categorized into grades I (0-29%), II (30-49%), III (50-59%), and IV (60-69%). The patient's stenosis grade was defined on the basis of the stenosis rate of the ICA side with most severe stenosis. Results: Stenosis progressed in 17.9% (64/358) of the vessels in 30.7% (55/179) of patients. The risk of stenosis progression increased as the severity of ICA stenosis increased. Patients with stenosis rates of above 50% are at a higher risk of stenosis progression than those with stenosis rate of < 50%. Relative to the patient group with an ICA stenosis rate of 0-29%, the adjusted odds ratios of stenosis progression were 2.33 (p = 0.03; 95% CI: 1.05~5.17), 3.50 (p = 0.09; 95% CI: 0.81~15.84), and 6.61 (p = 0.03; 95% CI: 1.01~39.61) in patient groups with ICA stenosis rates of 30-49%, 50-59%, and 60-69%, respectively. Hyper-LDL-cholesterolemia (Hyper-LDL-c) also increased the risk of stenosis progression, with an adjusted odds ratio of 2.22 (p = 0.03; 95% CI: 1.05~4.71). Conclusion: The rate of ICA stenosis progression increases with stenosis grade. Patients with ICA stenosis severity >50% and Hyper-LDL-c have high rates of stenosis progression. For the patients with stroke and ICA stenosis severity >50%, annual follow up through carotid artery ultrasonography may be necessary.