Cerebrospinal Fluid Biomarkers for the Diagnosis and Classification of Alzheimer's Disease Spectrum

Background@#Cerebrospinal fluid (CSF) biomarkers are increasingly used in clinical practice for the diagnosis of Alzheimer's disease (AD). We aimed to 1) determine cutoff values of CSF biomarkers for AD, 2) investigate their clinical utility by estimating a concordance with amyloid positron emission tomography (PET), and 3) apply ATN (amyloid/taueurodegeneration) classification based on CSF results. @*Methods@#We performed CSF analysis in 51 normal controls (NC), 23 mild cognitive impairment (MCI) and 65 AD dementia (ADD) patients at the Samsung Medical Center in Korea. We attempted to develop cutoff of CSF biomarkers for differentiating ADD from NC using receiver operating characteristic analysis. We also investigated a concordance between CSF and amyloid PET results and applied ATN classification scheme based on CSF biomarker abnormalities to characterize our participants. @*Results@#CSF Aβ42, total tau (t-tau) and phosphorylated tau (p-tau) significantly differed across the three groups. The area under curve for the differentiation between NC and ADD was highest in t-tau/Aβ42 (0.994) followed by p-tau/Aβ42 (0.963), Aβ42 (0.960), t-tau (0.918), and p-tau (0.684). The concordance rate between CSF Aβ42 and amyloid PET results was 92%. Finally, ATN classification based on CSF biomarker abnormalities led to a majority of NC categorized into A-T-N-(73%), MCI as A+T-N-(30%)/A+T+N+(26%), and ADD as A+T+N+(57%). @*Conclusion@#CSF biomarkers had high sensitivity and specificity in differentiating ADD from NC and were as accurate as amyloid PET. The ATN subtypes based on CSF biomarkers may further serve to predict the prognosis.

The Cortical Neuroanatomy Related to Specific Neuropsychological Deficits in Alzheimer's Continuum

BACKGROUND AND PURPOSE: In Alzheimer's continuum (a comprehensive of preclinical Alzheimer's disease [AD], mild cognitive impairment [MCI] due to AD, and AD dementia), cognitive dysfunctions are often related to cortical atrophy in specific brain regions. The purpose of this study was to investigate the association between anatomical pattern of cortical atrophy and specific neuropsychological deficits. METHODS: A total of 249 participants with Alzheimer's continuum (125 AD dementia, 103 MCI due to AD, and 21 preclinical AD) who were confirmed to be positive for amyloid deposits were collected from the memory disorder clinic in the department of neurology at Samsung Medical Center in Korea between September 2013 and March 2018. To analyze neuropsychological test-specific neural correlates representing the relationship between cortical atrophy measured by cortical thickness and performance in specific neuropsychological tests, a linear regression analysis was performed. Two neural correlates acquired by 2 different standardized scores in neuropsychological tests were also compared. RESULTS: Cortical atrophy in several specific brain regions was associated with most neuropsychological deficits, including digit span backward, naming, drawing-copying, verbal and visual recall, semantic fluency, phonemic fluency, and response inhibition. There were a few differences between 2 neural correlates obtained by different z-scores. CONCLUSIONS: The poor performance of most neuropsychological tests is closely related to cortical thinning in specific brain areas in Alzheimer's continuum. Therefore, the brain atrophy pattern in patients with Alzheimer's continuum can be predict by an accurate analysis of neuropsychological tests in clinical practice.

Correction to: Engineered M13 Nanofiber Accelerates Ischemic Neovascularization by Enhancing Endothelial Progenitor Cells

There is a minor spelling error in the last of name of the 9th author in the originally published article.

Reversible Cerebral Vasoconstriction Syndrome after Heart Transplantation

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by severe headaches with or without other acute neurological symptoms, and diffuse segmental constriction of cerebral arteries that resolves spontaneously within 3 months. A 44-year-old woman underwent heart transplantation due to primary amyloidosis with heart involvement. She started to have a seizure after three hours after the heart transplantation, and her consciousness was not recovered. Computed tomography and transcranial doppler sonography were used to diagnose RCVS, and contracted vessels were recovered after oral nimodipine administration.

Clinical significance of the lymph node ratio in N1 breast cancer

PURPOSE: The purpose of this study was to evaluate the prognostic value of the lymph node ratio (LNR), which was defined as the proportion of involved nodes of all dissected nodes, in pN1 breast cancer. MATERIALS AND METHODS: We retrospectively analyzed the clinical data of patients with pN1 breast cancer (N = 144) treated at Keimyung University Dongsan Medical Center, Daegu, Korea between 2001 and 2010. The median age was 46 years (range, 27 to 66 years). The LNR was 0.01–0.15 (low LNR) in 130 patients and >0.15 (high LNR) in 14 patients. Sixty-five patients (45.1%) had T1 tumors, 74 (51.4%) had T2 tumors, and 5 (3.5%) had T3 tumors. Eighty-eight patients (61.1%) underwent total mastectomy and 56 (38.9%) underwent partial mastectomy. Fifty-nine patients (41.0%) underwent radiotherapy and 12 (8.3%) underwent regional radiotherapy. The median follow-up period was 65 months. RESULTS: The 5- and 10-year disease-free survival (DFS) rates were 92.7% and 82.4%, respectively. Univariate analyses revealed that high LNR (p = 0.004), total mastectomy (p = 0.006), no local radiotherapy (p = 0.036), and stage T2 or T3 (p = 0.010) were associated with worse DFS. In multivariable analysis, only high LNR (p = 0.015) was associated with worse DFS. CONCLUSION: High LNR is an independent prognostic factor in pN1 breast cancer and could be an indication for adjuvant radiotherapy in these patients.

Clinical significance of the lymph node ratio in N1 breast cancer

PURPOSE: The purpose of this study was to evaluate the prognostic value of the lymph node ratio (LNR), which was defined as the proportion of involved nodes of all dissected nodes, in pN1 breast cancer. MATERIALS AND METHODS: We retrospectively analyzed the clinical data of patients with pN1 breast cancer (N = 144) treated at Keimyung University Dongsan Medical Center, Daegu, Korea between 2001 and 2010. The median age was 46 years (range, 27 to 66 years). The LNR was 0.01–0.15 (low LNR) in 130 patients and >0.15 (high LNR) in 14 patients. Sixty-five patients (45.1%) had T1 tumors, 74 (51.4%) had T2 tumors, and 5 (3.5%) had T3 tumors. Eighty-eight patients (61.1%) underwent total mastectomy and 56 (38.9%) underwent partial mastectomy. Fifty-nine patients (41.0%) underwent radiotherapy and 12 (8.3%) underwent regional radiotherapy. The median follow-up period was 65 months. RESULTS: The 5- and 10-year disease-free survival (DFS) rates were 92.7% and 82.4%, respectively. Univariate analyses revealed that high LNR (p = 0.004), total mastectomy (p = 0.006), no local radiotherapy (p = 0.036), and stage T2 or T3 (p = 0.010) were associated with worse DFS. In multivariable analysis, only high LNR (p = 0.015) was associated with worse DFS. CONCLUSION: High LNR is an independent prognostic factor in pN1 breast cancer and could be an indication for adjuvant radiotherapy in these patients.

Engineered M13 Nanofiber Accelerates Ischemic Neovascularization by Enhancing Endothelial Progenitor Cells

Dysfunction or loss of blood vessel causes several ischemic diseases. Although endothelial progenitor cells (EPCs) are a promising source for cell-based therapy, ischemia-induced pathophysiological condition limits the recovery rate by causing drastic cell death. To overcome this issue, we attempted to develop a cell-targeted peptide delivery and priming system to enhance EPCbased neovascularization using an engineered M13 bacteriophage harboring nanofibrous tubes displaying ∼ 2700 multiple functional motifs. The M13 nanofiber was modified by displaying RGD, which is an integrin-docking peptide, on the minor coat protein, and bymutilayering SDKPmotifs,which are the key active sites for thymosin b4, on themajor coat protein. The engineered M13 nanofiber dramatically enhanced ischemic neovascularization by activating intracellular and extracellular processes such as proliferation, migration, and tube formation in the EPCs. Furthermore, transplantation of the primed EPCs with the M13 nanofiber harboring RGD and SDKP facilitated functional recovery and neovascularization in a murine hindlimb ischemia model. Overall, this study demonstrates the effectiveness of theM13 nanofiber-based novel peptide deliveryandprimingstrategy inpromotingEPC bioactivity and neovessel regeneration. To our knowledge, this is first report onM13 nanofibers harboring dual functional motifs, the use of which might be a novel strategy for stem and progenitor cell therapy against cardiovascular ischemic diseases.

Multiple Intracranial Aneurysms Associated with Behçet's Disease

Behçet's disease is an inflammatory disorder involving multiple organs. Its cause is still unknown, but vasculitis is the major pathologic characteristic. The common vascular lesions associated with Behçet's disease are aneurysm formation, arterial or venous occlusive diseases, and varices. Arterial aneurysms mostly occur in large arteries. Intracranial aneurysms hardly occur with Behçet's disease. We would like to present a 41-year-old female patient with Behçet's disease who showed symptoms of severe headache due to subarachnoid hemorrhage. Brain computed tomography revealed multiple aneurysms. We also present a literature review of intracranial arterial aneurysms associated with Behçet's disease.

A Survey on the Prevalence of Musculoskeletal Symptoms and Related Factors among Korea Seamen / 예방의학회지

The purpose of this study is provide a basic data for the prevention and management of musculoskeletal symptoms in Korea seamen. 569 seamen's questionnaire had been acquired at Korea Marine Training and Research Institute from February 24 to March 31 in 1997. The results of this study were as follows; Prevalence in musculoskeletal symptom within recent 12 months was 68.5%. It was 76.3% in seamen who had graduated from colleges or universities and 56.0% in seamen who had graduated from elementary school(p<0.01). The more working hours(p<0.01), services on the vessel(p<0.01), and the less job atisfaction(p<0.05), the higher prevalence of musculoskeletal symptoms were. The distribution of musculoskeletal symptoms by the part of the body was turned out as Back ; 43.6%, knee ; 23.9%, shoulder ; 19.3%. The officers had more frequency of symptom around the neck than the ratings(p<0.01) and the seamen who work at the engine room were more frequent in elbow than those at deck department(p<0.05). In the duration of pain, 55.4% were less than one week, 20.6% less than 30 days, and 24.0% 30 days and more. the cause of symptom was turned out as 34.5% by excessive hard work and 30.1% was unknown. For the treatment of the musculoskeletal symptoms, 40.3% with symptomes did not have any medical treatment, 27.6% was self-treated and 22.7% was treated at hospital. This study shows that musculoskeletal disorders are seamen's important health problem and they can not properly take medical service due to the out of home for a long period as characteristics of occupation.

Anatomic Characteristics of Upper Eyelid Structures Important in Ptosis Surgery

Exact understanding of the upper eyelids is essential to the success of an anterior surgical approach for the correction of blepharoptosis. Therfore, we undertook this study using cadaver dissection, histologic sections, surgical observations, and review of MRI findings to gain a better understanding of the anatomical characteristics of the orbital septum and associated connective tissue structures which are important in ptosis surgery. The basic distinction of the upper eyelid structures between Oriental and Occidental is the relationship of the orbital septum and the levator aponeurosis. The orbital septum appears as a thick multilayered connective tissue originating just inside the superior orbital rim, but its inferior extension become thin progressively and blends with levator aponeurosis on an average of 1.6mm below the superior tarsal horder. Therefore the preaponeurotic fat is allowed to proceed to the anterior tarsal surface, resulting in a characteristic appearance of oriental eyelids. The levator aponeurosis maintains its thick and obvious structure continuously to the anterior tarsal surface near the lower margin of the upper lid. We resected levator aponeurosis with Muller's muscle which plays a important role in lid elevation for the correction of congenital htepharoptosis, and obtained excellent results.

Ophthalmic Complications After Paranasal Sinus Surgery

Various ophthalmic complications can occur after intranasal sinus surgery due to closed anatomic relation between orbit and paranasal sinuses. A study was undertaken to identify those patients with ophthalmic complication after intranasal sinus surgery. A consecutive series of 80 cases undergoing sinus surgery at department of ENT between Jan. 1992 and Jul. 1992 was studied prospectively. We recorded preoperative and postoperative best corrected visual acuity, intraocular pressure, exophthalmometric measurement, levator function, funding, lacrimal excretory function, extraocular muscle motility. Several patients were noticed a variety of ophthalmic problems after intranasal sinus surgery: 1 case of orbital hematoma and transient blepharoptosis, 2 cases of diplopia with limited duction, 4 cases of subcutaneous hemorrhage, tearing and blurring, 5 cases of conjunctival injection with chemosis, 7 cases of ocular discomfort, 42 cases of lid swelling. Orbital hematoma was treated with puncture and aspiration but other problems were recovered spontaneously within several days.

A Case of Acute Posterior Multifocal Placoid Pigment Epitheliopathy

Acute posterior multifocal placoid pigment epitheliopathy usually occurs in young or middle-aged adults and is usually bilateral. This syndrome is characterized by the acute onset of multiple, flat, yellow-white lesion of the posterior pole at the level of the retinal pigment epithelium and by the rapid loss of vision. These lesions resolve spontaneously, leaving extensive degeneration of pigment epithelium within a few weeks and visual acuity spontaneously improves in most cases. In the acute stage, fluorescein angiographic appearance of condition is characterized by placoid lesions blocking transmission of choroidal fluorescence in the initial phase, which are gradually stained and fluorescence faintly in the late phase. Older lesions represent residual defects in the pigment epithelium and appear as transmission defect without late staining or leakage of dye. Authors experienced and treated a case of acute posterior multifocal placoid pigment epitheliopathy in 19-years old male patient, and had a good visual improvement.