OBJECTIVE: A substantial portion of granulomatosis with polyangiitis (GPA) patients present with localized disease limited to the upper respiratory tract, however; disease spectrum and prognosis of these patients are unclear. The aim of this study is to describe the clinical characteristics and outcome of patients with localized GPA. METHODS: This was a retrospective descriptive case series of patients with a biopsy proven localized GPA presenting to a single tertiary rheumatology service between January 1995 and September 2015. RESULTS: A total of 5 patients, median age 56 years (range 48 to 59 years) at diagnosis and 80% female, were identified. The median follow-up period was 42 months (range 15 to 62 months). Diagnosis was delayed with median time to diagnosis of 12 months (range 3 to 36 months), and patients underwent 1-3 ear, nose, and throat surgeries during the period of diagnostic delay. Sinusitis was the most frequent symptom in all patients, followed by otomastoiditis with cranial nerve palsies (n=2) and orbital mass (n=1). Antineutrophil cytoplasmic antibody (ANCA) was positive initially in 2/5 patients (40%). Two patients with otomastoiditis and cranial nerve palsies progressed to systemic disease with ANCA positive conversion. These two cases along with a case with orbital mass were refractory to standard treatment of cyclophosphamide with glucocorticoids requiring rituximab treatment. CONCLUSION: Patients with localized GPA may progress to systemic disease over the disease course, and may have aggressive disease refractory to standard treatment. Close monitoring for systemic symptoms and repeated ANCA testing is required in patients with localized GPA.
Antibodies, Antineutrophil Cytoplasmic ; Biopsy ; Cranial Nerve Diseases ; Cyclophosphamide ; Diagnosis ; Ear ; Female ; Follow-Up Studies ; Glucocorticoids ; Granulomatosis with Polyangiitis* ; Humans ; Nose ; Orbit ; Pharynx ; Prognosis ; Respiratory System ; Retrospective Studies ; Rheumatology ; Rituximab ; Sinusitis

In post-stroke patients, the pain or paresthesia of the affected limb is common. These symptoms may be caused by a variety of pathologic conditions. Considering the debilitating effects of the pain, it is important to determine the exact cause and manage appropriately. A 41-year-old woman who had experienced a hemorrhagic lesion in the right basal ganglia and corona radiata 4 months previously presented with an irritating tingling sensation in her left upper extremity. She failed to respond to a number of treatment options including medications and physical agent modalities. Following a diagnosis of disputed thoracic outlet syndrome (TOS) caused by scalene muscle dysfunctions, she received ultrasound-guided electrical twitch-obtaining intramuscular stimulation (ETOIMS) which significantly alleviated the pain. This case suggests that the disputed TOS should be considered as one of the possible causes of post-stroke pain, and that detailed history-taking and physical examination, as well as imaging or electrophysiological studies, might be required for accurate diagnosis. Furthermore, ultrasound-guided ETOIMS can be used as a safe and minimally invasive technique for the treatment of the disputed TOS with fewer systemic and local side effects.
Adult ; Basal Ganglia ; Diagnosis ; Extremities ; Female ; Humans ; Muscles* ; Paresthesia* ; Physical Examination ; Sensation ; Stroke ; Thoracic Outlet Syndrome ; Upper Extremity*

Background and Objectives: The increased expression for the Fms-related tyrosine kinase-4 (FLT-4, known as VEGFR-3) is relevant to dysfunctional natural killer (NK) cells in acute myeloid leukemia (AML). MAZ51 (M), a VEGFR-3 inhibiting chemical, was effectively restored the function of NK cells via the high expression of interferon-gamma (IFN-γ) in NK cells, as shown in our previous study. Although tremendous amount of clinical data using peptides are currently available in real clinic, peptides targeting FLT-4 in modulating immune cells such as NK cells are not fully elucidated. Methods: and Results: In present study, we developed peptides targeting FLT-4 (P), which is inhibiting an affinity for AML-NK expressing FLT-4 in vitro and in vivo. Bone marrow (BM) and peripheral blood (PB) mononuclear cells (MNCs) from AML patients were treated with combinational cocktails of the three agents including P, M, ara-C (A) and FLT-4 expression and IFN-γ release were examined. In an AML mouse model, IFN-γ expression were examined in T and NK cells from mouse BM, spleen, and liver to address relevance between peptides and immune cell activation. We found that AML-NK cells both in human and mouse samples showed a gradual increase the IFN-γ levels compared to the controls. There was a trend toward a reduction in leukemic blasts in the BM, spleen, and liver from the AML mice, when we compared the effects of combinational treatments. Conclusions Our results suggest that the function of AML-NK cells was synergistically activated by P in combination with M or A.

Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common genetic cause of Parkinson's disease (PD). LRRK2 contains a functional kinase domain and G2019S, the most prevalent LRRK2 pathogenic mutation, increases its kinase activity. LRRK2 regulates mitochondria morphology and autophagy in neurons. LPS treatment increases LRRK2 protein level and mitochondrial fission in microglia, and down-regulation of LRRK2 expression or inhibition of its kinase activity attenuates microglia activation. Here, we evaluated the direct role of LRRK2 G2019S in mitochondrial dynamics in microglia. Initial observation of microglia in G2019S transgenic mice revealed a decrease in mitochondrial area and shortage of microglial processes compared with their littermates. Next, we elucidated the molecular mechanisms of these phenotypes. Treatment of BV2 cells and primary microglia with LPS enhanced mitochondrial fission and increased Drp1, a mitochondrial fission marker, as previously reported. Importantly, both phenotypes were rescued by treatment with GSK2578215A, a LRRK2 kinase inhibitor. Finally, the protein levels of CD68, an active microglia marker, Drp1 and TNF-α were significantly higher in brain lysates of G2019S transgenic mice compared with the levels in their littermates. Taken together, our data suggest that LRRK2 could promote microglial mitochondrial alteration via Drp1 in a kinase-dependent manner, resulting in stimulation of pro-inflammatory responses. This mechanism in microglia might be a potential target to develop PD therapy since neuroinflammation by active microglia is a major symptom of PD.
Animals ; Autophagy ; Brain ; Down-Regulation ; Mice ; Mice, Transgenic ; Microglia* ; Mitochondria ; Mitochondrial Dynamics* ; Neurons ; Parkinson Disease ; Phenotype ; Phosphotransferases*

The accuracy and convenience of continuous glucose monitoring (CGM), which efficiently evaluates glycemic variability and hypoglycemia, are improving. There are two types of CGM: professional CGM and personal CGM. Personal CGM is subdivided into real-time CGM (rt-CGM) and intermittently scanned CGM (isCGM). CGM is being emphasized in both domestic and foreign diabetes management guidelines. Regardless of age or type of diabetes, CGM is useful for diabetic patients undergoing multiple insulin injection therapy or using an insulin pump. rt-CGM is recommended for all adults with type 1 diabetes (T1D), and can also be used in type 2 diabetes (T2D) treatments using multiple insulin injections. In some cases, short-term or intermittent use of CGM may be helpful for patients with T2D who use insulin therapy other than multiple insulin injections and/or oral hypoglycemic agents. CGM can help to achieve A1C targets in diabetes patients during pregnancy. CGM is a safe and cost-effective alternative to self-monitoring blood glucose in T1D and some T2D patients. CGM used in diabetes management works optimally with proper education, training, and follow up. To achieve the activation of CGM and its associated benefits, it is necessary to secure sufficient repetitive training and time for data analysis, management, and education. Various supports such as compensation, insurance coverage expansion, and reimbursement are required to increase the effectiveness of CGM while considering the scale of benefit recipients, policy priorities, and financial requirements.