Stroke causes systemic immunosuppression. T lymphocytes are involved in infarct size in the early stages of stroke. However, the phenotypes of T lymphocytes and their functions in peripheral immune organs and the brain have not been well analyzed in the acute and chronic phases of stroke. Here, we investigated pathological phenotypic alterations in the systemic immune response, especially changes in T lymphocytes, from one day to six months after ischemic stroke in mice. Impairment in thymocyte numbers, development, proliferation, and apoptosis were observed for up to two weeks. The number of mature T cells in the spleen and blood decreased and showed reduced interferon-γ production. Increased numbers of CD4-CD8-CD3+ double-negative T cells were observed in the mouse brain during the early stages of stroke, whereas interleukin (IL)-10+Foxp3+ regulatory T lymphocytes increased from two weeks during the chronic phase. These phenotypes correlated with body weight and neurological severity scores. The recovery of T lymphocyte numbers and increases in IL-10+Foxp3+ regulatory T lymphocytes may be important for long-term neurological outcomes. Dynamic changes in T lymphocytes between the acute and chronic phases may play different roles in pathogenesis and recovery. This study provides fundamental information regarding the T lymphocyte alterations from the brain to the peripheral immune organs following stroke.

Stroke causes systemic immunosuppression. T lymphocytes are involved in infarct size in the early stages of stroke. However, the phenotypes of T lymphocytes and their functions in peripheral immune organs and the brain have not been well analyzed in the acute and chronic phases of stroke. Here, we investigated pathological phenotypic alterations in the systemic immune response, especially changes in T lymphocytes, from one day to six months after ischemic stroke in mice. Impairment in thymocyte numbers, development, proliferation, and apoptosis were observed for up to two weeks. The number of mature T cells in the spleen and blood decreased and showed reduced interferon-γ production. Increased numbers of CD4-CD8-CD3+ double-negative T cells were observed in the mouse brain during the early stages of stroke, whereas interleukin (IL)-10+Foxp3+ regulatory T lymphocytes increased from two weeks during the chronic phase. These phenotypes correlated with body weight and neurological severity scores. The recovery of T lymphocyte numbers and increases in IL-10+Foxp3+ regulatory T lymphocytes may be important for long-term neurological outcomes. Dynamic changes in T lymphocytes between the acute and chronic phases may play different roles in pathogenesis and recovery. This study provides fundamental information regarding the T lymphocyte alterations from the brain to the peripheral immune organs following stroke.

Purpose: Preoperative tumor size is associated with clinical stage, treatment plan and even survival rate of patient. We investigated the accuracy of tumor size estimation between magnetic resonance imaging (MRI) and ultrasonography (US) findings, comparing these with pathologic tumor size in the diagnosis of early breast carcinoma. Methods: Between 2011 and 2016, 136 patients with early breast cancer were analyzed and their tumor size on US and MRI findings were compared with their pathologic tumor size retrospectively. The background parenchymal enhancement of MRI was categorized as minimal, mild, moderate, and extreme. The patients who underwent neoadjuvant chemotherapy, had positive resection margins, underwent excisional biopsy for cancer diagnosis, and had non-mass lesions on MRI scans, were excluded. Results: In all, 83.1% of the cases showed concordance between MRI findings and pathologic tumor size within 0.5cm. MRI overestimated the findings by 10.3% and underestimated them by 6.6%; 78.7% showed concordance between US findings and pathologic tumor size within 0.5cm. US overestimated the findings by 5.9% and underestimated them by 15.4%. The tumor size on MRI (r=0.87) showed a stronger correlation to the pathologic tumor size than that on US (r=0.64) in early breast cancer patients. US had a tendency to underestimate the tumor size. The degree of breast parenchyma did not affect the accuracy of the measurement of preoperative tumor size. Conclusion MRI is relatively more accurate than US for assessing preoperative tumor size in breast cancer patients. US tends to underestimate tumor size.

BACKGROUND: Few scales are currently available to evaluate changes in hand volume. We aimed to develop a hand grading scale for quantitative assessments of dorsal hand volume with additional consideration of changes in skin texture; to validate and prove the precision and reproducibility of the new scale; and to demonstrate the presence of clinically significant differences between grades on the scale. METHODS: Five experienced plastic surgeons developed the Hand Volume Rating Scale (HVRS) and rated 91 images. Another five plastic surgeons validated the scale using 50 randomly selected images. Intra- and inter-rater agreement was calculated using the weighted kappa statistic and intraclass correlation coefficients (ICCs). Paired images were also evaluated to verify whether the scale reflected clinical differences. RESULTS: The intra-rater agreement was 0.95 (95% confidence interval, 0.922–0.974). The interrater ICCs were excellent (first rating, 0.94; second rating, 0.94). Image pairs that differed by 1, 2, and 3 grades were considered to contain clinically relevant differences in 80%, 100%, and 100% of cases, respectively, while 84% of image pairs of the same grade were found not to show clinically relevant differences. This confirmed that the scale of the HVRS corresponded to clinically relevant distinctions. CONCLUSIONS: The scale was proven to be precise, reproducible, and reflective of clinical differences.
Asian Continental Ancestry Group ; Hand ; Humans ; Plastics ; Rejuvenation ; Skin ; Skin Aging ; Surgeons ; Weights and Measures

Korea is located within the East Asian-Australian flyway of wild migratory birds during the fall and winter seasons. Consequently, the likelihood of introduction of numerous subtypes and pathotypes of the Avian influenza (AI) virus to Korea has been thought to be very high. In the current study, we surveyed wild bird feces for the presence of AI virus that had been introduced to Korea between September 2017 and February 2018. To identify and characterize the AI virus, we employed commonly used methods, namely, virus isolation (VI) via egg inoculation, real-time reverse transcription-polymerase chain reaction (rRT-PCR), conventional RT-PCR (cRT-PCR) and a newly developed next generation sequencing (NGS) approach. In this study, 124 out of 11,145 fresh samples of wild migratory birds tested were rRT-PCR positive; only 52.0% of VI positive samples were determined as positive by rRT-PCR from fecal supernatant. Fifty AI virus specimens were isolated from fresh fecal samples and typed. The cRT-PCR subtyping results mostly coincided with the NGS results, although NGS detected the presence of 11 HA genes and four NA genes that were not detected by cRT-PCR. NGS analysis confirmed that 12% of the identified viruses were mixed-subtypes which were not detected by cRT-PCR. Prevention of the occurrence of AI virus requires a workflow for rapid and accurate virus detection and verification. However, conventional methods of detection have some limitations. Therefore, different methods should be combined for optimal surveillance, and further studies are needed in aspect of the introduction and application of new methods such as NGS.
Animals ; Birds ; Feces ; Influenza in Birds ; Korea ; Methods ; Ovum ; Seasons

Spinal accessory nerve (SAN) injury mostly occurs during surgical procedures. SAN injury caused by manipulation therapy has been rarely reported. We present a rare case of SAN injury associated with manipulation therapy showing scapular winging and droopy shoulder. A 42-year-old woman visited our outpatient clinic complaining of pain and limited active range of motion (ROM) in right shoulder and scapular winging after manipulation therapy. Needle electromyography and nerve conduction study suggested SAN injury. Physical therapy (PT) three times a week for 2 weeks were prescribed. After a total of 6 sessions of PT and modality, the patient reported that the pain was gradually relieved during shoulder flexion and abduction with improved active ROM of shoulder. Over the course of 2 months follow-up, the patient reported almost recovered shoulder ROM and strength as before. She did not complain of shoulder pain any more.
Accessory Nerve Injuries* ; Accessory Nerve* ; Adult ; Ambulatory Care Facilities ; Electromyography ; Female ; Follow-Up Studies ; Humans ; Musculoskeletal Manipulations* ; Needles ; Neural Conduction ; Range of Motion, Articular ; Shoulder ; Shoulder Pain

OBJECTIVE: To identify the prevalence of antiphospholipid antibodies (aPL) in systemic lupus erythematosus (SLE) patients and determine the relationship between aPL and the clinical outcomes. METHODS: SLE patients with aPL test results within 2 years of enrollment were selected from Korean lupus network study. They were classified into two groups: aPL (+) group, patients positive for at least one aPL, and aPL (−) group, patients without an aPL. The clinical characteristics of the two groups were compared and the role of aPL in the risk of chronic kidney disease (CKD) in SLE patients was examined. RESULTS: Among the 469 SLE patients, 69 (14.7%) had at least one aPL. The prevalence of cerebrovascular disease and CKD was higher in the aPL (+) group than in the aPL (−) group (10.1% vs. 1.8% and 13.8% vs. 5.1%, p < 0.05). Multivariable regression analysis showed that the aPL positivity (odds ratio=3.93, 95% confidence interval=1.48∼10.47) was associated with the risk of CKD after adjusting for age, disease duration, and lupus nephritis history. CONCLUSION: Among the 469 SLE patients, 69 (14.7%) had at least one aPL. The prevalence of cerebrovascular disease and CKD was higher in the aPL (+) group than in the aPL (−) group (10.1% vs. 1.8% and 13.8% vs. 5.1%, p < 0.05). Multivariable regression analysis showed that the aPL positivity (odds ratio=3.93, 95% confidence interval=1.48∼10.47) was associated with the risk of CKD after adjusting for age, disease duration, and lupus nephritis history.
Antibodies, Antiphospholipid* ; Cerebrovascular Disorders ; Humans ; Lupus Erythematosus, Systemic* ; Lupus Nephritis ; Prevalence ; Renal Insufficiency, Chronic

OBJECTIVE: To estimate the cardiovascular (CV) and gastrointestinal (GI) risks of etoricoxib in the treatment of osteoarthritis (OA) compared to a placebo and other non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: A systematic review of randomized, controlled trials (RCTs) of etoricoxib were performed. Bayesian network meta-analysis was used over a duration of 12 weeks. The incidence of CV and GI events for a duration ≥26 weeks were also tabulated and presented using descriptive statistics. RESULTS: From this search, 10 studies were identified. Of these, 6 and 5 RCTs that measured the CV and GI events at 12 weeks were included in meta-analysis. They showed that etoricoxib did not increase the CV events compared to the placebo or NSAIDs during the 12 week period (odds ratio [OR]=0.59 compared to celecoxib, OR=0.89 with ibuprofen, OR=0.70 with placebo, and OR=2.16 with naproxen). The risk of GI events was comparable to that of most comparators, with the exception of naproxen, which had a significantly lower risk of GI events (OR=0.18) during the 12 week period. For a duration ≥26 weeks, the incidence of CV and GI events with etoricoxib increased with increasing duration. CONCLUSION: Etoricoxib is an alternative short-term treatment option for OA, showing comparable CV and GI complications to other NSAIDs. Nevertheless, further studies will be needed to elucidate the long-term safety of etoricoxib in the treatment of OA.
Anti-Inflammatory Agents ; Anti-Inflammatory Agents, Non-Steroidal ; Celecoxib ; Ibuprofen ; Incidence ; Naproxen ; Osteoarthritis*

Glucagon like peptide-1 (GLP-1) stimulates glucose-dependent insulin secretion. Dipeptidyl peptidase-4 (DPP-4) inhibitors, which block inactivation of GLP-1, are currently in clinical use for type 2 diabetes mellitus. Recently, GLP-1 has also been reported to have neuroprotective effects in cases of cerebral ischemia. We therefore investigated the neuroprotective effects of GLP-1 receptor (GLP-1R) agonist, exendin-4 (ex-4), after cerebral ischemia-reperfusion injury. Transient middle cerebral artery occlusion (tMCAO) was induced in rats by intracerebroventricular (i.c.v.) administration of ex-4 or ex9-39. Oxygen-glucose deprivation was also induced in primary neurons, bEnd.3 cells, and BV-2. Ischemia-reperfusion injury reduced expression of GLP-1R. Additionally, higher oxidative stress in SOD2 KO mice decreased expression of GLP-1R. Downregulation of GLP-1R by ischemic injury was 70% restored by GLP-1R agonist, ex-4, which resulted in significant reduction of infarct volume. Levels of intracellular cyclic AMP, a second messenger of GLP-1R, were also increased by 2.7-fold as a result of high GLP-1R expression. Moreover, our results showed that ex-4 attenuated pro-inflammatory cyclooxygenase-2 (COX-2) and prostaglandin E₂ after MCAO. C-Jun NH₂ terminal kinase (JNK) signaling, which stimulates activation of COX-2, was 36% inhibited by i.c.v. injection of ex-4 at 24 h. Islet-brain 1 (IB1), a scaffold regulator of JNK, was 1.7-fold increased by ex-4. GLP-1R activation by ex-4 resulted in reduction of COX-2 through increasing IB1 expression, resulting in anti-inflammatory neuroprotection during stroke. Our study suggests that the anti-inflammatory action of GLP-1 could be used as a new strategy for the treatment of neuroinflammation after stroke accompanied by hyperglycemia.
Animals ; Brain Ischemia ; Cyclic AMP ; Cyclooxygenase 2 ; Diabetes Mellitus, Type 2 ; Down-Regulation ; Glucagon* ; Glucagon-Like Peptide 1 ; Glucagon-Like Peptide-1 Receptor ; Hyperglycemia ; Infarction, Middle Cerebral Artery ; Insulin ; Mice ; Neurons ; Neuroprotection ; Neuroprotective Agents ; Oxidative Stress ; Phosphotransferases ; Rats ; Reperfusion Injury ; Second Messenger Systems ; Stroke*

The use of novel oral anticoagulants (NOACs) has increased in recent times in an effort to overcome the shortcomings of warfarin. They are being used primarily for the prevention of thrombosis caused by atrial fibrillation and offer the advantages of having fewer drug interactions than warfarin, no dietary restrictions, and no requirement for regular blood tests. Although there is reportedly less postoperative bleeding even if the drug is not discontinued during procedures that can cause local bleeding, such as dental procedures, no well-designed clinical studies have assessed postoperative bleeding associated with the use of these drugs. This article reports a case of a 74-year-old male patient who was taking rivaroxaban. The patient underwent a dental implant procedure after discontinuing rivaroxaban for one day and subsequently suffered delayed bleeding on postoperative day 6. Accordingly, this article also reports that the use of NOACs may also lead to delayed bleeding.
Aged ; Anticoagulants* ; Atrial Fibrillation ; Dental Implants ; Drug Interactions ; Emergencies ; Hematologic Tests ; Hemorrhage* ; Humans ; Male ; Rivaroxaban ; Thrombosis ; Warfarin