Baroreflex Sensitivity as a Surrogate Biomarker for Concurrently Assessing the Severity of Arterial Stiffness and Cardiovascular Autonomic Neuropathy in Individuals with Type 2 Diabetes.

This study aimed to investigate whether baroreflex sensitivity (BRS) could serve as a reliable metric for assessing cardiovascular autonomic neuropathy (CAN) and concurrently act as a surrogate biomarker for evaluating the severity of arterial stiffness and CAN in individuals diagnosed with type 2 diabetes mellitus (T2DM). Participants underwent brachial-ankle pulse wave velocity (baPWV) as well as autonomic function evaluations encompassing the Sudoscan-based modified composite autonomic scoring scale (CASS), baroreflex sensitivity, and heart rate variability in time domains and frequency domains. Linear regression analysis was performed to evaluate the influence of independent variables on baPWV and modified CASS. Participants with higher baPWV values were older, with longer diabetes duration, lower body weight, body mass index, waist circumference, elevated systolic and diastolic blood pressure, and mean arterial blood pressure. They also exhibited a higher prevalence of retinopathy as the underlying disease and reduced estimated glomerular filtration rate. Multiple linear regression analysis revealed that age and BRS were significantly associated with baPWV while diabetes duration, UACR, and BRS were significantly associated with modified CASS. Our study confirms the significant association of BRS with baPWV and modified CASS in T2DM, highlighting its pivotal role in linking microvascular and macrovascular complications. This supports BRS as a surrogate marker for assessing both the severity of arterial stiffness and cardiovascular autonomic neuropathy in T2DM, enabling the early identification of complications.

Prognostic factors and treatment responses among patients with gross residual disease in differentiated thyroid cancer.

BACKGROUND: Various postoperative staging systems were developed to assess the outcome of differentiated thyroid cancer from initial risk after surgery to dynamic changing prognosis during follow-up. The objective of our retrospective cohort study was to identify risk factors contributing to macroscopic positive surgical margin (R2 resection) and parameters in discriminating the treatment responses and prognosis among R2 patients. METHODS: In total, 242 differentiated thyroid cancer patients with extrathyroidal extension who underwent a thyroidectomy at Kaohsiung Chang Gung Memorial Hospital between January 2013 and July 2018, were included. The patients were grouped according to the presence or absence of gross residual disease (R2). The R2 patients were further classified into two categories according to their treatment response into excellent and nonexcellent groups. The parameters and treatment outcomes were compared between these groups. RESULTS: The mean follow-up time was 45.3 months. Two hundred seven (85.5%) patients had either surgery-free or microscopic margins (R0/R1), while 35 (14.5%) had R2 resection. In the R2 group (n = 35), 15 (42.9%) patients achieved an excellent response, while 20 (57.1%) achieved a nonexcellent response. Statistically significant differences were observed in the extent of neck dissection, TSH-Tg level, post-RAI Tg level, nodal status, and recurrence between the two groups. The Kaplan-Meier curves for 5-year local and distant recurrence-free survival of R0/R1 versus R2 patients were 90.0% versus 66.3%, and 98.4% versus 90.7%, respectively ( p < 0.001). Among the R2 patients, the excellent responders had a higher local recurrence-free survival than nonexcellent responders (93.3% vs. 45.1%, p = 0.008). CONCLUSION: There are significant disparities in recurrence-free survival among R2 patients with different treatment responses. The nodal status of papillary thyroid cancer and thyroglobulin level after thyroidectomy and RAI were factors contributing to difference in their treatment responses.

Recombinant human thyrotropin versus thyroid hormone withdrawal preparation for radioiodine ablation in differentiated thyroid cancer: Experience in a South Taiwanese medical center.

This retrospective study was designed to compare the treatment response of patients with differentiated thyroid cancer (DTC) prepared for radioiodine ablation (RIA) with thyroid hormone withdrawal (THW) or recombinant human thyrotropin (rhTSH) stimulation. Patients with DTC were followed-up retrospectively between 2013 and 2018 in Kaohsiung Chang Gung Memorial Hospital, Taiwan. We compared the excellent response ratios between THW (49.9%) and rhTSH (50.1%) stimulation. Patients were then divided into subgroups, on the basis of age, sex, extrathyroidal extension, lymph node metastasis, and tumor-node-metastasis stage, for analysis. In all, 647 patients were followed-up after RIA. The ratios of THW or rhTSH use in the different subgroups were not statistically significant. In all the patients, the excellent response rate with THW and rhTSH was 80% and 76.5%, respectively, which was not statistically significant. The subgroup analysis, including age, sex, extrathyroidal extension, lymph node metastasis, and tumor-node-metastasis stage (low and high risk), showed similar results. Furthermore, the logistic regression analysis revealed no statistically significant differences among the subgroups. The multivariate analysis showed extrathyroidal extension, lymph node metastasis, and high I131 dose were the prognostic factors affecting the excellent response rate. In conclusion, the THW and rhTSH preparations for RIA were similar in terms of the excellent response rates and subgroup clinical outcomes.

Hypocalcemia Is a Common Risk Factor for Osteoporosis in Taiwanese Patients with Cushing's Syndrome.

Background: Osteoporosis is a cardinal manifestation of Cushing's syndrome. There is a lack of relevant research on risk factors for osteoporosis among patients with Cushing's syndrome (CS) in Taiwan. Thus, this study was designed to explore the possible risk factors of osteoporosis. Methods: We gathered patients with a diagnosis of CS between 2001 and 2017 in the Chang Gung Research Database (CGRD). We extracted data including diagnoses and biochemistry from hospital records. The diagnosis of CS was based on ICD-9-CM codes (255.0). Osteoporosis was defined by a T value equal to or less than −2.5 in BMD examination and hypocalcemia was defined as serum calcium concentrations < 8.0 mg/dL. Results: A total of 356 patients with CS who made regular visits to the outpatient department were enrolled in this study. The mean age was 68.6 years, and 74.9% of the patients were female. Of them, 207 patients (58.1%) were diagnosed with osteoporosis. Multivariable logistic regression models indicated that serum calcium level was negatively associated with osteoporosis (OR 0.70, CI 0.54−0.91, p < 0.001) after adjustment for age, sex, and other confounding risk factors. In addition, hypocalcemia was associated with heart failure (HF) (OR 2.14, CI 1.02−4.47, p < 0.05), stroke (OR 2.58, CI 1.21−5.46, p < 0.05) and osteoporosis (OR 3.04, CI 1.24−7.41, p < 0.05) in multivariate analysis. Conclusions: Our study found that lower serum calcium levels were common among patients with CS and osteoporosis. Furthermore, CS patients with HF or stroke had high proportion of hypocalcemia. Therefore, these patients must pay more attention to adequate calcium supplementation and undergo the appropriate osteoporosis drug treatment to reduce the risk of subsequent fracture and disability.

Analysis of overall survival in differentiated thyroid cancer patients with double primary malignancy.

Differentiated thyroid cancer (DTC) survivors are at increased risk of developing double primary malignancy (DPM). The aim of this study was to investigate clinicopathological characteristics and survival in DTC patients diagnosed with DPM. A total of 975 patients with DTC diagnosed between 2013 and 2017, treated, and followed at a medical center in Taiwan were retrospectively reviewed. Data from enrolled patients were analyzed for differences in prognosis dependent on the presence of DPM, and which clinicopathological variables affected their prognosis. Among 975 thyroid cancer patients, 94 (9.6%) were diagnosed with DPMs and 16 (1.6%) patients died of any cause. DPM patients had a greater proportion of males, had a higher mean age, more commonly presented with a thyroid mass incidentally by imaging and cervical lymph node metastases, showed a more advanced thyroid cancer stage, and had a higher proportion of lymph node metastases. Overall survival (OS) was significantly lower in patients diagnosed with DPM. Male gender (hazard ratio [HR] = 4.597), two or more DPMs (HR = 8.071), and shorter time interval between two cancers occurrences (HR = 7.101) were significantly risk factors for DPM-related death. In conclusion, the risk of developing DPM in DTC patients was elevated in older, male patients with an advanced tumor-node-metastasis stage. DPM adversely affected the OS of thyroid cancer patients. Male gender, two or more DPMs, and shorter time interval between occurrences were significant risk factors for OS in DPM patients.

Association between Pro12Ala polymorphism and albuminuria in type 2 diabetic nephropathy.

AIMS/INTRODUCTION: Diabetic nephropathy (DN) is a complication of diabetes mellitus that is characterized by the gradual loss of kidney function, which results in increased levels of albumin in the urine. The Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-γ2 gene has been confirmed to improve insulin sensitivity, but its association with susceptibility to DN in patients with type 2 diabetes remains inconclusive. MATERIALS AND METHODS: To examine whether the Pro12Ala polymorphism leads to the development of DN, a case-control study was carried out in 554 patients with type 2 diabetes. The genotypes of Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma 2 gene were analyzed by real-time polymerase chain reaction with TaqMan® probe genotyping assay in all patients. RESULTS: The mean age of the study population was 57.7 ± 8.8 years, with average diabetes duration of 12.8 ± 6.9 years. The prevalence of albuminuria was 43.5%. The frequency of genotype Pro12Pro, Pro12Ala and Ala12Ala genotype were 92.6%, 7.0%, 0.4% in our study population, and 90.4%, 8.9% and 0.7% in normal urinary albumin-to-creatinine ratio group, respectively. The Ala carriers (Pro12Ala + Ala12Ala) had significantly lower urinary albumin-to-creatinine ratio (15.0 vs 20.5 mg/g, P = 0.001) and better renal function (estimated glomerular filtration rate 81.8 [69.8-97.6] vs 78.7 mL/min/1.73 m2 [61.6-96.2]; P = 0.05) compared with those with the genotype Pro12Pro. After adjustment for age, sex and other confounders, the odds ratio of albuminuria for the Ala12 allele was 0.428 (95% confidence interval 0.195-0.940, P = 0.034]). CONCLUSIONS: Our results suggest that the peroxisome proliferator-activated receptor gamma 2 Ala12 variant has significant protective effects against albuminuria and DN.

The spatial-verbal difference in the n-back task: an ERP study.

The spatial-verbal dichotomy of working memory tasks was investigated using event-related potentials. Using an n-back task with three levels of n (0-, 1-, and 2-back), participants either matched words presented at a fixed screen position (verbal task) or matched the locations of non-word symbols presented at various positions across the screen (spatial task). Therefore, these two conditions were separated without confound of location and stimulus. Factors of match and task loading (Stimulus and N-Back effect) were found significant in P2a, N2 and P3, whereas domain-specific lateralization (Hemisphere x Task interaction, the feature of perception) was found significant in EPC, P2a and N2 but not in P3. These results hint time course of match (before P2a beginning, 200 ms) and perception (before P3 beginning, 300 ms).

Distinctions between spatial and verbal working memory: a study using event-related potentials.

BACKGROUND: The main manifestation of dementia is a defect in working memory. N-back tasks are frequently used in research on working memory. Researchers can study differences between different loadings by controlling N factors. Furthermore, the interface of N-back tasks can be verbal or visual-spatial. METHODS: Event-related potentials under verbal and spatial tasks and different loadings were recorded using a digital electroencephalogram, and analyzed together with behavior results. RESULTS: The differences between spatial and verbal processing were found mainly inter-component, where P3 was enhanced in verbal tasks and P2a was enhanced in spatial tasks. Furthermore, P3 was only enhanced in the left hemisphere in the target stimulus. N2 was enhanced by verbal non-target with similar amplitudes. The lateralization was not significant between spatial and verbal tasks. CONCLUSION: The difference between spatial and verbal N-back tasks is not only lateralization but also more complex presentations, including P2a (for spatial tasks),P3 (for verbal tasks), and N2 (for non-target detection in verbal tasks).

Sub-processes of working memory in the N-back task: an investigation using ERPs.

OBJECTIVE: The N-back task is frequently used in working memory studies. N-parameters allow experimental psychologists to analyze the sub-processes of N-back tasks in addition to general processing. However, previous imaging studies have not closely scrutinized these sub-processes. In the current study, three sub-processes in the N-back task were proposed using a logical task analysis: matching, replacement and shift. Domain-specific lateralization in spatial and verbal working memory was investigated in terms of this model. METHODS: This model was tested with two ERP experiments during N-back tasks, one conceptual (top-down) and one data-driven (bottom-up). RESULTS: Domain-specific lateralization was observed as predicted in the shift sub-process of the conceptual task and in the replacement sub-process of the data-driven task. Match-specific lateralization was also found. CONCLUSIONS: The results support our three-sub-process model of the N-back task and our hypothesis that replacement is a data-driven process with a posterior locus whereas shift is a more conceptual process with a more frontal locus. SIGNIFICANCE: The proposed model correctly predicted ERP patterns in conceptual and data-driven N-back tasks and is potentially useful in understanding the neurophysiologic basis of N-back task performance. The similarity between match- and domain-specific lateralization in N-back tasks raised several issues for further investigation.

Interference from the irrelevant domain in n-back tasks: an ERP study.

Selective attention and interference from the irrelevant domain are frequently neglected factors in working memory experiments. Here identical stimuli were employed in n-back tasks under spatial and verbal task instructions to test whether information in the irrelevant domain was really irrelevant. The results reveal interference from the irrelevant domain in the replacement sub-process of the n-back task, and highlight the importance of taking cross-domain interference into account when drawing conclusions from neuropsychological experiments.

Maternally inherited diabetes and deafness (MIDD) syndrome: a clinical and molecular genetic study of a Taiwanese family.

We report on a case of a 48-year-old woman presenting with maternally inherited diabetes mellitus and deafness (MIDD) syndrome. Molecular genetic analysis and clinical evaluation were conducted in the patient and her 4 children to investigate the interrelation between an MIDD-associated mitochondrial DNA (mtDNA) mutation and clinical manifestations. Various symptoms and markers of MIDD, including seizures, migraines, short stature, mental retardation, and stroke-like episodes, were reviewed. Diabetes mellitus (DM) was studied by oral glucose tolerance and glucagon stimulation tests. Hearing impairment was determined by standard hearing tests and a brainstem auditory evoked potential test. The A3243G and T3271C transitional mutations of mtDNA were investigated from muscle and/or leukocytes and hair follicles. Mitochondrial-related symptoms were not found in the children, although they all harbored a heteroplasmic A3243G transition of mtDNA, as detected in screened samples. For the patient, the proportion of mutant mtDNA was highest in muscle cells followed by hair follicles and then leukocytes. Moreover, the proportion of mutant mtDNA was also higher in hair follicles than in leukocytes for asymptomatic family members. This Taiwanese MIDD family was found to have the A3243G point mutation as revealed from molecular genetic studies of leukocytes, hair follicles, and muscle tissue. However, no correlation was found between the proportion of mutant mtDNA and clinical features of any family member.