Ankle-Brachial Index Is Independently Associated With Cardiovascular Outcomes and Foot Ulcers in Asian Patients With Type 2 Diabetes Mellitus.

Background and Aims: The ankle-brachial index (ABI) is an efficient tool for objectively documenting the presence of lower-extremity peripheral arterial disease (PAD). The predictive factors of cardiovascular events and diabetic foot ulcer were not clear from the ABI examination in Taiwanese patients with type 2 diabetes mellitus (DM). Methods: We enrolled 482 patients with type 2 DM who regularly visited the outpatient department of Chang Gung Memorial Hospital and received ABI as well as brachial-ankle pulse wave velocity (ba-PWV) examinations from 2010 to 2017. Age, gender, PAD symptoms, comorbidities, family history of chronic diseases, lifestyle (smoking, alcohol consumption, and exercise), height, weight, waist circumference, monofilament testing and foot ulcer status were studied. Results: There were 104 (22%) patients (mean age, 67.8 years) with the ABI <1.0. These patients with low ABI (ABI<1.0) had a significantly older age (p=0.001), higher delta PWV (p<0.001), higher rates of stroke (p=0.007), myocardial infarction (p=0.016), and foot ulcer (p=0.039). In a multivariable analysis model, the adjusted odds ratio (aOR) for myocardial infarction, stroke, and foot ulcers associated with low ABI were 1.219 (0.397-3.743, p=0.729), 1.204 (0.556-2.610, p=0.638), and 2.712 (1.199-6.133, p=0.017), respectively. The patients with low PWV (PWV<1400 cm/s) were significantly younger (p<0.001) and had a lower rate of hypertension (p<0.001), and higher percentages of stroke (p=0.027) and dialysis (p=0.041) family history. Conclusions: Low ABI was associated with cardiovascular events and diabetic foot ulcer independently in patients with type 2 DM.

Association of stiff-person syndrome with autoimmune endocrine diseases.

BACKGROUND: Stiff-person syndrome (SPS) and its subtype, stiff limb syndrome (SLS), are rare neurological disorders characterized by progressive muscular rigidity and spasms. Glutamic acid decarboxylase (GAD) is the enzyme that catalyzes the production of γ-aminobutyric acid (GABA), a major inhibitory neurotransmitter of the central nervous system. SPS is an autoimmune disease triggered by anti-glutamic acid decarboxylase antibody (anti-GAD Ab). Clinically, anti-GAD Ab is associated with SPS, type 1 diabetes mellitus (T1DM), and other autoimmune diseases. AIM: To investigate the link of autoimmune endocrine disorders with anti-GAD Ab in SPS subjects. METHODS: This retrospective study was approved by the Institutional Review Board of Chang Gung Memorial Hospital, Taiwan. We collected the patients with SPS from January 2001 to June 2018. By reviewing 14 patients from medical records, we analyzed the clinical findings with coexisting autoimmune diseases, particularly diabetes mellitus and thyroid disease, which are associated with anti-GAD antibody titers or other immunological test results (anti-thyroid peroxidase and anti-nuclear antibodies). We also evaluated malignancies, major complications, and reported treatment to improve symptoms. Anti-GAD antibodies were measured using radioimmunoassay and enzyme-linked immunosorbent assay (ELISA). The cut-off values of these tests are < 1 U/mL and < 5 U/mL, respectively. RESULTS: The median age of all patients was 39.3 (range, 28.0-54.0) years with a median follow-up period of 6.0 (2.7-13.3) years. Five (35.7%) patients were female; twelve (85.7%) were diagnosed with classic SPS and two (14.3%) with SLS. The median age of onset of symptoms was 35.0 (26.0-56.0) years with a median follow-up duration of 9.0 (2.1-14.9) years in the classic SPS group; the SLS group had a median age of onset of 46.7 years and a shorter follow-up duration of 4.3 years. Among nine classic SPS patients who underwent the anti-GAD Ab test, three were anti-GAD Ab seropositive and each of these three patients also had T1DM, latent autoimmune diabetes in adults, and autoimmune thyroid disease, respectively. In contrast, other rare autoimmune diseases co-existed in six anti-GAD Ab seronegative SPS patients. None of the SLS patients had additional autoimmune diseases. CONCLUSION: While typical clinical symptoms are crucial for the diagnosis of SPS, the presence of anti-GAD autoantibody may consolidate the diagnosis and predict the association with other autoimmune diseases.

Computer-Aided Diagnostic Technique in 2-Deoxy-2-[18F]fluoro-D-glucose-Positive Thyroid Nodule: Clinical Experience of 74 Non-thyroid Cancer Patients.

This study verified the value of a computer-aided diagnosis (CAD) technique assisting in ultrasonography (US) diagnosis of 2-deoxy-2-[18F]fluoro-D-glucose (18FDG)-avid thyroid incidentalomas on positron emission tomography. A total of 82 18FDG-avid thyroid incidentalomas from 74 non-thyroid cancer patients were retrospectively analyzed with respect to US and CAD parameters (anechoic area, hyper-echoic foci, hypo-echogenicity, heterogeneity, margin, taller-than-wide shape, eccentric area) and were compared with 38 other non-18FDG-avid nodules found in the same patient group. Fine-needle aspiration cytology or surgical intervention pathology was performed for diagnosis. No significant differences in nodule size or CAD parameters were found in 18FDG-avid nodules reported as benign, indeterminate or malignant. Significantly more taller-than-wide nodules were thyroid originating than metastatic (0.30 vs. 0.16, p < 0.05). Nevertheless, combined CAD and positron emission tomography/computed tomography scores and a discrimination point of 4 resulted in a sensitivity of 75% and a specificity of 80% in prediction of incidentaloma benignity.

The Arctic mutation accelerates Aß aggregation in SDS through reducing the helical propensity of residues 15-25.

Mutations within the ß-amyloid peptide (Aß) sequence that cause early onset familial Alzheimer's disease (FAD) have been shown to promote Aß aggregation. How these FAD-related mutants increase the aggregative ability of Aß is not fully understood. Here, we characterized the effect of the Arctic variant (E22G) on the conformational stability of Aß using various forms of spectroscopy and kinetic analyses, including nuclear magnetic resonance (NMR), circular dichroism (CD) spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy and transmission electron microscopy (TEM). The E22G mutation in the Arctic variant reduced the α-helical propensity and conformational stability of Aß on residues 15-25. This mutation also caused an increase in both α-helix-to-ß-strand conversion and fibril nucleation rates. Our results suggest that the α-helical propensity of residues 15-25 may play a determinant role in the aggregative ability of Aß. This may provide a structural basis for understanding the molecular mechanism of Aß aggregation.

Effect of alanine replacement of l17 and f19 on the aggregation and neurotoxicity of arctic-type aß40.

Alzheimer's disease is the most common form of neurodegenerative disease. Beta-amyloid peptides (Aß) are responsible for neuronal death both in vitro and in vivo. Previously, L17 and F19 residues were identified as playing key roles in the stabilization of the Aß40 conformation and in the reduction of its neurotoxicity. In this study, the effects of L17A/F19A mutations on the neurotoxicity of Aß genetic mutant Arctic-type Aß40(E22G) were tested. The results showed that compared to Aß40(E22G), Aß40(L17A/F19A/E22G) reduced the rate of conformation conversion, aggregation, and cytotoxicity, suggesting that L17 and F19 are critical residues responsible for conformational changes which may trigger the neurotoxic cascade of Aß. Aß40(L17A/F19A/E22G) also had decreased damage due to reactive oxygen species. The results are consistent with the discordant helix hypothesis, and confirm that residues 17-25 are in the discordant helix region. Compared to Aß40(L17A/F19A), reduction in aggregation of Aß40(L17A/F19A/E22G) was less significantly decreased. This observation provides an explanation based on the discordant helix hypothesis that the mutation of E22 to G22 of Aß40(E22G) alters the propensity of the discordant helix. Arctic-type Aß40(E22G) aggregates more severely than wild-type Aß40, with a consequential increase in toxicity.

Aß40(L17A/F19A) mutant diminishes the aggregation and neurotoxicity of Aß40.

Aggregated ß-amyloid peptides (Aß) are neurotoxic and responsible for neuronal death both in vitro and in vivo. From the structural point of view, Aß self-aggregation involves a conformational change in the peptide. Here, we investigated the relationship between conformational changes and amino acid residues of Aß(40). Urea unfolding in combination with NMR spectroscopy was applied to probe the stabilization of Aß(40) conformation. L17 and F19 residues were found more sensitive to environmental changes than the other residues. Replacement of these two residues with alanine could stabilize the conformation of Aß(40). Further analysis indicated that the Aß(40)(L17A/F19A) mutant could diminish the aggregation and reduce the neurotoxicity. These results suggest that L17 and F19 are the critical residues responsible for conformational changes which may trigger neurotoxic cascade of Aß(40).

Characteristics of Klebsiella pneumoniae bacteremia in community-acquired and nosocomial infections in diabetic patients.

BACKGROUND: Although diabetes mellitus is known as a major risk factor for Klebsiella pneumoniae infection, the differences in clinical characteristics between community-acquired and nosocomial K. pneumoniae bacteremia in diabetic patients have been rarely reported. METHODS: This retrospective analysis enrolled 193 adult diabetic patients with K. pneumoniae bacteremia hospitalized between January 2005 and December 2006. The chi-squared test, analysis of variance (ANOVA), Student's t test, Fisher exact test, and Cox regression model were used for statistical analysis. RESULTS: Of the enrolled patients, 147 had community-acquired infections and 46 had nosocomial infections. Compared with the community group, the nosocomial group had higher rates of in-hospital mortality (41.3% vs. 18.4%, p=0.001), malignancy (50.0% vs. 19.0%, p<0.001), and leukopenia (21.7% vs. 5.4%, p=0.001) but had lower levels of serum C-reactive protein (124.3 mg/L vs. 188.7 mg/L, p=0.018) and HbA1c (8.1% vs. 9.5%, p=0.025). The rate of infection with the extended-spectrum ß-lactamase-producing strain (ESBL infection) in the nosocomial group was 11 times higher than that in the community group (45.7% vs. 4.1%, p<0.001). ESBL infection accounted for 53% of mortality in the nosocomial group. Pneumonia was more common in the nosocomial group, while local abscess was more common in the community group. The risk factors for mortality were pneumonia, leukopenia, cirrhosis, and a high serum creatinine ratio (creatinine level at admission/baseline). CONCLUSIONS: The nosocomial group had more ESBL infections which might account for the higher mortality. The HbA1c level during the course of infection did not affect the outcome. Pneumonia, leukopenia, cirrhosis, and a high serum creatinine ratio at admission were the risk factors for poor outcome.

Obstructive sleep apnea syndrome in an adolescent girl with hypertrophic lingual thyroid.

We present a 14-year-old girl whose initial diagnosis was obstructive sleep apnea syndrome (OSAS) with symptoms of habitual snore, sleep breath holding, shortness of breath, and lump in throat. Lingual thyroid was diagnosed by thyroid scan and histology, and was treated by radioactive iodine therapy and endoscopic carbon dioxide laser therapy. Her OSAS completely subsided after lingual thyroid surgery. Physicians should be aware of rare causes of OSAS in children, such as lingual thyroid and certainly if accompanied by difficulties in swallowing and speech problems.

Adrenal incidentalomas in Taiwan: high prevalence and malignancy rate.

BACKGROUND: The endocrine adrenal gland has 3 zones comprised of the cortex and medulla. The character of multi-hormonal expression results in multiple clinical manifestations. To define the clinical characteristics of adrenal tumors in Taiwan, we reviewed 336 pathologically proven adrenal tumors at Chang Gung Memorial Hospital in Linkou. METHODS: We retrospectively analyzed 258 pathologically proven adrenal tumors with sufficient data treated from 1983 to 2000. Among them, 174 (67%) were functional and 84 (33%) were nonfunctional. The diagnosis was based on clinical features, hormonal status, imaging studies, and pathology. RESULTS: Of the 258 patients, 161 were women (mean age, 38.5 +/- 15.4; range, 1-75 years) and 97 men (mean age, 41.6 +/- 17.8; range, 1-81 years). The prevalence of cortical tumors was much higher in females than in males. Fifty-two percent of patients with an adrenal tumor were diagnosed at an age between 30 and 50 years. Incidentalomas (N = 84) accounted for about 1/3 of total tumor cases. Of the 46 cases proven to be malignant, 40 (87%) were found incidentally. All malignant tumors had a diameter of greater than 3 cm. Postoperative adrenal insufficiency was present in 18% of cases, and overall mortality in this study was 0.4%. CONCLUSIONS: In our series, adrenal incidentalomas corresponded to about 1/3 of adrenal tumors and accounted for 87% of malignancies. It is mandatory to increase medical attention for incidentally found adrenal masses in Taiwan. Those incidentalomas with a diameter of more than 3 cm should undergo a pathological examination.