Association of sodium-glucose cotransporter 2 inhibitors with risk of incident dementia and all-cause mortality in older patients with type 2 diabetes: A retrospective cohort study using the TriNetX US collaborative networks.

BACKGROUND: Limited evidence exists to support any specific medication over others to prevent dementia in older patients with type 2 diabetes (T2D). We investigated whether treatment with sodium-glucose cotransporter 2 (SGLT-2) inhibitors is associated with a lower risk of incident dementia and all-cause mortality, relative to dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RA). METHODS: In this retrospective, active-comparator cohort study, we used data from the TriNetX electronic health records network. Our primary cohort comprised patients with T2D aged ≥50 years, registered between January 2012 and December 2022. Patients with a history of dementia were excluded. We used Kaplan-Meier survival analysis to estimate the incidence of dementia and all-cause mortality in our cohort after they had used glucose-lowering drugs for at least 12 months. Propensity score matching was performed to balance the SGLT-2 inhibitor, DPP-4 inhibitor and GLP-1 RA cohorts. Subgroup analyses for sex and age were also conducted. RESULTS: Our first cohort comprised 193 948 patients treated with metformin and SGLT-2 inhibitors and an equal number of patients treated with metformin and DPP-4 inhibitors. In this cohort, the risk of dementia and all-cause mortality was lower in patients treated with SGLT-2 inhibitors than in those treated with DPP-4 inhibitors (hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.59-0.65, for dementia; HR: 0.54, 95% CI: 0.52-0.56, for all-cause mortality). Our second cohort comprised 165 566 patients treated with metformin and SGLT-2 inhibitors and an equal number of patients treated with metformin and GLP-1 RAs. In this cohort, the risk of dementia and all-cause mortality was lower in those treated with SGLT-2 inhibitors than in those treated with GLP-1 RAs (HR: 0.92, 95% CI: 0.87-0.98, for dementia; HR: 0.88, 95% CI: 0.85-0.91, for all-cause mortality). CONCLUSIONS: The use of SGLT-2 inhibitor was associated with a lower risk of incident dementia and all-cause mortality in older adults with T2D compared to DPP-4 inhibitor and GLP-1 RA.

A Case Report: An Acute Spinal Epidural Hematoma after Acupuncture Mimicking Stroke.

BACKGROUND: Spinal epidural hematoma (SEH) after acupuncture is rare and may present with acute or subacute onset and varied symptoms, making it difficult to diagnose. This condition can mimic acute stroke, so it is vital to establish a clear diagnosis before considering thrombolytic therapy, which could be disastrous if applied inappropriately. CASE REPORT: We describe a 52-year-old man who presented to our emergency department (ED) with acute onset of unilateral weakness of the limbs for 3.5 h immediately after receiving acupuncture at the bilateral neck and back. The acute stroke team was activated. In the ED, computer tomography angiography from the aortic arch to the head revealed spinal epidural hematoma. The patient was admitted to the ward for conservative treatment and was discharged with subtle residual symptoms of arm soreness 5 days later. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Acute spinal epidural hematoma rarely presents with unilateral weakness of the limbs, mimicking a stroke. Because inappropriate thrombolysis can lead to devastating symptoms, spinal epidural hematoma should be excluded when evaluating an acute stroke patient with a history of acupuncture who is a possible candidate for thrombolytic therapy.

Monoclonal antibodies for chronic pain: a practical review of mechanisms and clinical applications.

Context: Monoclonal antibodies are being investigated for chronic pain to overcome the shortcomings of current treatment options. Objective: To provide a practical overview of monoclonal antibodies in clinical development for use in chronic pain conditions, with a focus on mechanisms of action and relevance to specific classes. Methods: Qualitative review using a systematic strategy to search for randomized controlled trials, systematic and nonsystematic (narrative) reviews, observational studies, nonclinical studies, and case reports for inclusion. Studies were identified via relevant search terms using an electronic search of MEDLINE via PubMed (1990 to June 2017) in addition to hand-searching reference lists of retrieved systematic and nonsystematic reviews. Results: Monoclonal antibodies targeting nerve growth factor, calcitonin gene-related peptide pathways, various ion channels, tumor necrosis factor-α, and epidermal growth factor receptor are in different stages of development. Mechanisms of action are dependent on specific signaling pathways, which commonly involve those related to peripheral neurogenic inflammation. In clinical studies, there has been a mixed response to different monoclonal antibodies in several chronic pain conditions, including migraine, neuropathic pain conditions (e.g., diabetic peripheral neuropathy), osteoarthritis, chronic back pain, ankylosing spondylitis, and cancer. Adverse events observed to date have generally been mild, although further studies are needed to ensure safety of monoclonal antibodies in early stages of development, especially where there is an overlap with non-pain-related pathways. High acquisition cost remains another treatment limitation. Conclusion: Monoclonal antibodies for chronic pain have the potential to overcome the limitations of current treatment options, but strategies to ensure their appropriate use need to be determined.

Exome sequencing identifies GNB4 mutations as a cause of dominant intermediate Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of inherited neuropathies. Mutations in approximately 45 genes have been identified as being associated with CMT. Nevertheless, the genetic etiologies of at least 30% of CMTs have yet to be elucidated. Using a genome-wide linkage study, we previously mapped a dominant intermediate CMT to chromosomal region 3q28-q29. Subsequent exome sequencing of two affected first cousins revealed heterozygous mutation c.158G>A (p.Gly53Asp) in GNB4, encoding guanine-nucleotide-binding protein subunit beta-4 (Gß4), to cosegregate with the CMT phenotype in the family. Further analysis of GNB4 in an additional 88 unrelated CMT individuals uncovered another de novo mutation, c.265A>G (p.Lys89Glu), in this gene in one individual. Immunohistochemistry studies revealed that Gß4 was abundant in the axons and Schwann cells of peripheral nerves and that expression of Gß4 was significantly reduced in the sural nerve of the two individuals carrying the c.158G>A (p.Gly53Asp) mutation. In vitro studies demonstrated that both the p.Gly53Asp and p.Lys89Glu altered proteins impaired bradykinin-induced G-protein-coupled-receptor (GPCR) signaling, which was facilitated by the wild-type Gß4. This study identifies GNB4 mutations as a cause of CMT and highlights the importance of Gß4-related GPCR signaling in peripheral-nerve function in humans.

Pulse Blood Pressure Correlates with Late Outcome in Acute Ischemic Stroke without Significant Culprit Artery Stenosis.

BACKGROUND: This study was conducted to test the hypothesis that elevated blood pressure at the early stage is associated with unfavorable outcome in acute ischemic stroke patients with stenosis of less than 50% of the culprit artery. METHODS: Patients with acute ischemic stroke onset within 48 hours and stenosis of less than 50% of the culprit artery from a prospective stroke registry were analyzed. A modified Rankin Scale score of 1 or lower at 3 months was defined as a favorable late outcome. Univariate and multivariate logistic regression analyses were used to analyze the association between hemodynamic parameters and outcome. RESULTS: One hundred thirty-six patients fulfilled the selection criteria. Patients with favorable outcome had lower pulse pressure at emergency department (ED) triage, lower systolic blood pressure (SBP) at 24 hours, lower pulse pressure at 24 hours, and lower heart rate (HR) at 24 hours. The univariate logistic regression analysis showed that history of stroke, elevated SBP at 24 hours, elevated HR at 24 hours, elevated pulse pressure at 24 hours, and higher National Institutes of Health Stroke Scale score at ED triage were associated with a less favorable late outcome. Two separate models of multivariate logistic regression analyses showed that pulse pressure at ED triage and pulse pressure at 24 hours, respectively, were significantly associated with less favorable outcome. CONCLUSIONS: Elevated pulse pressure at the early stage is independently associated with unfavorable late outcome in acute ischemic stroke patients with culprit artery stenosis less than 50%.

Comparison of activities of daily living impairments in Parkinson's disease patients as defined by the Pill Questionnaire and assessments by neurologists.

OBJECTIVES: To compare the clinical judgment of experienced neurologists after interviewing Parkinson's disease (PD) patients and their caregivers with the use of the Pill Questionnaire to determine the presence of impairments on activities of daily living (ADL). BACKGROUND: ADL impairment is a criterion for the diagnosis of dementia associated with PD. The Pill Questionnaire has been recommended as a screening tool to assess ADL impairment in PD patients, but its usefulness and validity have not been fully investigated. METHODS: We recruited idiopathic PD patients from 12 hospitals in Taiwan, and the patients underwent clinical assessments, a neuropsychological test battery and the Unified Parkinson Disease Rating Scale evaluation. The Pill Questionnaire was administered by study assistants. Patient and caregiver interviews were performed by experienced neurologists who were blinded to the Pill Questionnaire results. RESULTS: In total, 284 PD patients (mean age 71.8±9 years, mean education 8.7±5.3 years, mean disease duration 5.4±5.3 years) were recruited. 63 patients showed ADL impairment by the Pill Questionnaire, and 108 patients showed ADL impairment by neurologists' clinical interviews. κ Statistics showed moderate agreement between the two methods (κ=0.521, p<0.001). Of the 108 patients who were diagnosed with ADL impairment by neurologists, only 56 patients (51.9%) showed impairment according to the Pill Questionnaire. Most of the missed patients had milder cognitive impairment and lower motor disability. CONCLUSIONS: A comprehensive interview is essential to determine the presence of ADL impairment in PD patients, especially in patients with early PD.

Usefulness of phase-contrast magnetic resonance imaging for diagnosis and treatment evaluation in patients with SIH.

BACKGROUND: Most diagnostic tools for spontaneous intracranial hypotension (SIH) are either invasive or occasionally inconsistent with the clinical condition. In this study, we examined the cerebrospinal fluid (CSF) dynamics in SIH using phase-contrast magnetic resonance (PC-MR) imaging. MATERIALS AND METHOD: Seventeen SIH patients and 32 healthy individuals, matched by sex and age, were recruited. Each person underwent brain and PC-MR imaging using 3-Tesla MRI. We evaluated the differences in image parameters among patients during the initial and recovery stages against the status of the control group. RESULTS: SIH patients had lower CSF flow-volume, flux, peak velocity, and higher systolic-to-diastolic time ratio, as well as systolic-to-diastolic volume ratio compared to the control group and the conditions when they recovered. The flow time and volume of the diastolic phase markedly increased after treatment. The discriminating power of PC-MR for SIH was good. Diffuse pachymeningeal enhancement and venous engorgement were present when their PC-MR values were lower than the cut-off values for SIH diagnosis. The headache scores correlated with the peak velocity and pituitary volume. CONCLUSION: Noninvasive PC-MR could provide valid parameters for diagnosis and treatment follow-up in SIH patients. It may be more sensitive than conventional brain MRI.

Paraneoplastic Limbic Encephalitis Associated with Adenocarcinoma of Lung.

PURPOSE: Paraneoplastic limbic encephalitis (PLE) is a rare, immune-mediated entity. We present an unusual case of a patient who has double cancers and two different paraneoplastic neurological syndromes. CASE REPORT: A 58-year-old gentleman has histories of adenocarcinoma of lung and malignant thymoma associated with myasthenia gravis, which underwent surgery and chemotherapy 3 years ago. This time, he presented to our ward with rapidly progressive memory decline and myoclonic jerks in his limbs for two weeks. Magnetic resonance imaging (MRI) of brain showed increased signal intensity over bilateral mesial temporal regions on T2 Fluid Attenuated Inversion Recover (FLAIR) series. Chest computed tomography showed cancer recurrence. He received steroid pulse therapy firstly and right lung lower lobe lobectomy later. Pathology report of the tumor was recurrent adenocarcinoma. After the immunotherapy and tumor resection, his mentality improved gradually. Six months later, brain MRI showed resolution of bilateral temporal hyperintensity with residual mesial temporal atrophy. CONCLUSION: From our case, we would like to emphasize that paraneoplastic limbic encephalitis should be considered among the differential diagnosis of rapidly progressive dementia associated with myoclonus, along with other neurodegenerative diseases. Depending on its underlying malignancy, the cognitive impairment may be substantially reversible, despite atrophy of mesial temporal lobes.

Impact of olfactory function on the trajectory of cognition, motor function, and quality of life in Parkinson's disease.

Background: Olfactory dysfunction in Parkinson's disease (PD) is associated with more severe phenotypes, but trajectories of cognitive function, disease severity, and subdomains of quality-of-life measurements in patients with distinct olfactory profiles remain underexplored. Objective: To analyze the influence of olfaction on trajectories of clinical parameters in patients with PD. Design: Retrospective cohort study. Subjects: From October 2016 to May 2021, the study tracked 58 participants over 3 years. Participants completed follow-up assessments using tools including the Chinese version of the University of Pennsylvania's Smell Identification Test (UPSIT), Montreal Cognitive Assessment (MoCA), Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale, and the Chinese translation of the 39-item Parkinson's Disease Questionnaire (PDQ-39). Methods: Participants were divided into anosmia (UPSIT < 19) and non-anosmia (UPSIT ≥ 19) groups based on initial scores. Generalized estimating equations and repeated measures correlations were used to examine longitudinal associations and correlations between olfaction and clinical parameters. Results: Divergent cognitive trajectories were observed between groups. The anosmia group exhibited a faster cognitive decline (adjusted B [beta coefficient] = -1.8, p = 0.012) according to the interaction effect of olfaction and time on the MoCA score. The anosmia group exhibited no longitudinal correlation between cognition and olfactory function but showed correlations with age (rrm [coefficient of repeated measures correlation] = -0.464, p = 0.004) and disease duration (rrm = -0.457, p = 0.005). The non-anosmia group's UPSIT scores decreased over time (B = -2.3, p = 0.005) alongside a significant correlation with motor function (rrm = -0.479, p = 0.006). Conclusion: The anosmia group's accelerated cognitive decline correlated with age and disease duration, but not olfactory function, suggesting a poor cognitive outcome in this population despite the lack of longitudinal correlation between cognition and olfaction. The non-anosmia group exhibited progressive olfactory degradation and notable correlations between motor function and UPSIT scores, implying pathological accumulation in the olfactory structure and basal ganglia.

Diabetic peripheral neuropathy: age-stratified glycemic control.

Background: We explore the effect of suboptimal glycemic control on the incidence of diabetic peripheral neuropathy (DPN) in both non-elderly and elderly patients with type 2 diabetes mellitus (T2DM). Methods: A 6-year follow-up study (2013-2019) enrolled T2DM patients aged >20 without DPN. Participants were classified into two groups: those below 65 years (non-elderly) and those 65 years or older (elderly). Biochemical measurements, including glycated hemoglobin (HbA1C), were recorded regularly. DPN was diagnosed using the Michigan Neuropathy Screening Instrument examination. The outcome was DPN occurrence in 2019. Results: In 552 enrollments (69% non-elderly), DPN occurred in 8.4% non-elderly and 24.0% elderly patients. A higher initial HbA1C level was significantly linked with a higher risk of future DPN in the non-elderly group (adjusted odds ratio [AOR] 1.46, 95% CI 1.13-1.89, p=0.004). In comparison, HbA1c at the end of the study period was not associated with DPN in the non-elderly group (AOR 1.17, 95% CI 0.72-1.90, p=0.526). In the elderly group, no statistical relationship was found between HbA1C levels and DPN, either in 2013 or in 2019. Conclusion: Suboptimal glycemic control at baseline, rather than at the end of the study period, predicts an increased risk of future DPN in individuals with T2DM under age 65. This correlation is not seen in elderly patients. Therefore, we recommend implementing enhanced glycemic control early in middle-aged T2DM patients and propose individualized therapeutic strategies for diabetes in different age groups.

The greatest loss of unpleasant smells may be related to the risk of more severe PD symptoms.

Background: Limited research has explored the relationship between the valence of olfactory dysfunction and PD clinical symptoms. This study aimed to investigate correlations between the emotional valence of olfactory impairment and different domains of PD symptoms. Methods: PD patients who fulfilled the clinically probable PD diagnostic criteria of the International Parkinson and Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's Disease were recruited from the Center for Parkinson and Movement Disorders at Taichung Veterans General Hospital between October 2016 and April 2022. Demographic data and serial clinical assessments were collected, including the traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC) and Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Thirty-five odors from the UPSIT-TC were classified into neutral, pleasant or unpleasant groups. Group comparisons, correlation analyses, and linear regression analyses were conducted to examine the relationship between olfactory impairment of UPSIT-TC odors, considering emotional valence, and MDS-UPDRS subscores across various domains. Results: A total of 176 PD patients were recruited for analysis. Patients in the predominantly neutral/unpleasant odor impairment groups had higher MDS-UPDRS part III scores compared to those in the predominantly pleasant odor impairment group (pleasant vs. neutral vs. unpleasant odor impairment groups: 26.79 ± 13.59 vs. 35.33 ± 16.36 vs. 31.57 ± 12.37, p = 0.009). This trend was also noted in MDS-UPDRS rigidity, bradykinesia, and akinetic-rigid subscores (p = 0.003, p = 0.012, and p = 0.001, respectively). Correlation analysis revealed a weak but significant correlation between rigidity/akinetic-rigid subscores and misidentification numbers for neutral/unpleasant odors (all p < 0.05), with age, gender, LEDD, and disease duration as covariates. All significances were retained in the linear regression analysis. Conclusion: Our results emphasize the link between olfactory impairment of specific emotional valence, neutral/unpleasant odors, and PD severity, particularly with respect to akinetic-rigid symptoms. A concise olfactory test that focuses on both neutral and unpleasant odors may offer deeper insights into PD symptoms.

Sequential change in olfaction and (non) motor symptoms: the difference between anosmia and non-anosmia in Parkinson's disease.

Introduction: Hyposmia is a common prodrome in patients with Parkinson's disease (PD). This study investigates whether olfactory changes in PD differ according to the degree of olfactory dysfunction and whether there are changes in motor and non-motor symptoms. Methods: The 129 subjects with PD were divided into two groups: anosmia and non-anosmia. All cases were reassessed within 1-3 years after the initial assessment. The assessment included the MDS-Unified PD Rating Scale (MDS-UPDRS), the University of Pennsylvania Smell Identification Test (UPSIT), Beck's Depression Inventory-II (BDI-II), Montreal Cognitive Assessment (MoCA), and equivalence dose of daily levodopa (LEDD). The generalized estimating equation (GEE) model with an exchangeable correlation structure was used to analyze the change in baseline and follow-up tracking and the disparity in change between these two groups. Results: The anosmia group was older and had a longer disease duration than the non-anosmia group. There was a significant decrease in UPSIT after follow-up in the non-anosmia group (ß = -3.62, p < 0.001) and a significant difference in the change between the two groups (group-by-time effect, ß = 4.03, p < 0.001). In the third part of the UPDRS motor scores, there was a tendency to increase the score in the non-anosmia group compared to the anosmia group (group-by-time effect, ß = -4.2, p < 0.038). There was no significant difference in the group-by-time effect for UPDRS total score, LEDD, BDI-II, and MoCA scores. Discussion: In conclusion, this study found that olfactory sensation may still regress in PD with a shorter disease course without anosmia, but it remains stable in the anosmia group. Such a decline in olfaction may not be related to cognitive status but may be associated with motor progression.

The association between hyperlipidemia, lipid-lowering drugs and diabetic peripheral neuropathy in patients with type 2 diabetes mellitus.

AIMS: Previous studies showed conflicting relationship between hyperlipidemia, lipid-lowering therapy and diabetic peripheral neuropathy (DPN). As most of these works emerges from the Western and Australian countries, our study aims to investigate whether hyperlipidemia or lipid-lowering therapy (LLT) is associated with DPN in Taiwanese patients with type 2 diabetes (T2D). METHODS: A cross-sectional, hospital-based observation study in adults with T2D was conducted from January to October 2013. DPN was screened using the Michigan Neuropathy Screening Instrument. Data were obtained at the time of enrollment, including medication usage, anthropometric measurements and laboratory examinations. RESULTS: 2,448 participants were enrolled, 524 (21.4%) of whom had DPN. Patients with DPN had significantly lower plasma total cholesterol (185.6 ± 38.6 vs 193.4 ± 42.3 mg/dL) and low-density lipoprotein cholesterol levels (114.6 ± 32.7 vs 119 ± 30.8 mg/dL). Multivariate analysis demonstrated that neither hyperlipidemia (adjusted OR (aOR), 0.81; 95% confidence interval (CI), 0.49-1.34) nor LLT (aOR, 1.10; 95% CI, 0.58-2.09) was associated with DPN. Subgroup analysis revealed that neither total cholesterol (aOR, 0.72; 95% CI, 0.2-2.62), low-density lipoprotein cholesterol levels (aOR, 0.75; 95% CI, 0.2-2.79), statin (aOR, 1.09; 95% CI, 0.59-2.03) nor fibrate (aOR, 1.73; 95% CI, 0.33-1.61) was associated with DPN. CONCLUSION: Our results suggest that neither hyperlipidemia nor lipid-lowering medication was associated with DPN in adults with T2D. DPN is a multifactorial disease, and our findings indicate that lipid metabolism may play a minor role in its pathogenesis.

UPSIT subitems may predict motor progression in Parkinson's disease.

Background: The relationship between hyposmia and motor progression is controversial in Parkinson's disease (PD). The aim of this study was to investigate whether preserved identification of Chinese-validated University of Pennsylvania Smell Identification Test (UPSIT) odors could predict PD motor progression. Methods: PD patients with two consecutive clinical visits while taking medication were recruited. Based on mean changes in Movement Disorder Society Unified Parkinson's Disease Rating Scale part 3 score and levodopa equivalent daily dosage, the participants were categorized into rapid progression, medium progression, and slow progression groups. Odors associated with the risk of PD motor progression were identified by calculating the odds ratios of UPSIT item identification between the rapid and slow progression groups. Receiver operating characteristic curve analysis of these odors was conducted to determine an optimal threshold for rapid motor progression. Results: A total of 117 PD patients were screened for group classification. Preserved identification of neutral/pleasant odors including banana, peach, magnolia, and baby powder was significantly correlated with rapid motor progression. The risk of rapid progression increased with more detected risk odors. Detection of ≥1.5 risk odors could differentiate rapid progression from slow progression with a sensitivity of 85.7%, specificity of 45.8%, and area under the receiver operating characteristic curve of 0.687. Conclusion: Preserved identification of neutral/pleasant odors may help to predict PD motor progression, and detection of ≥1.5 UPSIT motor progression risk odors could improve the predictive power. In PD patients with a similar level of motor disability during initial screening, preserved pleasant/neutral odor identification may imply relatively better cortical odor discriminative function, which may suggest the body-first (caudo-rostral) subtype with faster disease progression.

Dysosmia Is a Predictor of Motor Function and Quality of Life in Patients with Parkinson's Disease.

(1) Background: The correlation between dysosmia with quality of life (QoL) in patients with PD was rarely reported. The study aimed to examine the effect of dysosmia on motor function and QoL in PD. (2) Methods: This cross-sectional study, performed between October 2016 and February 2021, recorded the traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT), the Montreal Cognitive Assessment (MoCA), the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS UPDRS), and the 39-item Parkinson's Disease Questionnaire (PDQ-39) in patients with PD. UPSIT = 19 was applied to separate the total anosmia and non-anosmia groups. (3) Results: 243 patients with PD were recruited. The total anosmia group had higher MDS UPDRS total, part II, and part III scores than the non-anosmia group. They also had worse scores on the dimensions of activities of daily living (ADL) and cognition of the PDQ-39 than the non-anosmia group. The UPSIT score correlated MDS UPDRS part III score (p < 0.0001), PDQ-39 ADL quartile (p = 0.0202), and Dopamine transporter scan (p = 0.0082) in the linear regression. (4) Conclusions: Dysosmia in PD predicted a phenotype with defective motor function, ADL, and cognition QoL. The findings supported the olfactory transmission of α-synuclein to the cortices, substantia nigra.

Renal impairment is one of appropriate predictors of future diabetic peripheral neuropathy: a hospital-based 6-year follow-up study.

The relationship between renal impairment and diabetic peripheral neuropathy (DPN) remains inconclusive. We aim to investigate the risk factors for the occurrence of DPN in Taiwanese adults with type 2 diabetes mellitus (T2DM) and focus on renal impairment. A hospital-based study was conducted from 2013 to 2019 and 552 Taiwanese people who had T2DM without DPN at baseline were enrolled. DPN was diagnosed using the Michigan Neuropathy Screening Instrument. Potential risk factors were recorded, including patient's sociodemographic factors, current medication usage and biochemical markers. As of 2019, 73 developed DPN and 479 had no DPN. The cumulative incidence during the 6-year period was 13.22%. Multivariable logistic regression analysis revealed that lower estimated glomerular filtration rate (eGFR) (odds ratio [OR] 0.98, p = 0.005), advanced age (OR 1.06, p = 0.001), increased body weight (OR 1.04, p = 0.018), duration of DM (OR 1.05, p = 0.036) and male gender (OR 3.69, p = 0.011) were significantly associated with future DPN. In addition, patients with T2DM under the age of 65 with higher serum creatinine concentration (OR 8.91, p = 0.005) and higher baseline HbA1C (OR 1.71, p < 0.001) revealed significantly associated with future DPN. In conclusion, this is the first large scaled hospital-based study with long term follow-up to investigate risk factors for DPN in Taiwanese. Lower eGFR and higher serum creatinine concentration, particularly in people under the age of 65, are predictors of future DPN in Taiwanese people with T2DM. Other predictors included advanced age, increased body weight, duration of DM, male gender for all ages and HbA1c in enrolled patients under the age of 65. Our study not only confirms the association between renal impairment and future DPN but also provides a commonly available assessment to predict the future DPN.

Safety and efficacy of pulse-induced contour cardiac output monitoring in elderly patients with coronary artery disease and severe heart failure at coronary care units.

Background: The optimal treatment for elderly patients with severe heart failure depends on the accurate assessment of their hemodynamic status. Due to its less invasive nature, the safety and efficacy of invasive pulse-induced contour cardiac output (PiCCO)-based hemodynamic monitoring remains uncertain. Methods: This was a prospective observational study. Between January 2016 and July 2020, 190 elderly patients with severe heart failure were consecutively enrolled. The PiCCO group (89 patients) and non-invasive hemodynamic monitoring group (101 patients) were observed. Hospital stays results were evaluated. Results: No significant difference in clinical data (P > 0.05) or the incidence of 1-month mortality (16.0 vs. 35.0%, P = 0.141) were observed between groups. The coronary care unit (CCU) stay was shorter in the PiCCO group than in the non-invasive group (40.0 vs. 43.0%, P = 0.049). Indicators such as low Extravascular Lung Water Index (EVLWI), high Body Mass Index (BMI), low Pulmonary Artery Pressure (PAP), and high Left Ventricular Ejection Time (LVET), were associated with favorable clinical results. Conclusion: Early invasive PiCCO monitoring is safe in critically ill elderly patients with severe heart failure. The hospital stay was reduced using PiCCO monitoring. These encouraging PiCCO results favor its use in elderly patients with severe heart failure at CCUs.

BRAP Activates Inflammatory Cascades and Increases the Risk for Carotid Atherosclerosis.

The BRCA-1 associated protein gene (BRAP) was recently identified as a susceptibility gene for myocardial infarction (MI). In the present study we aimed to decipher the association between the BRAP polymorphism and carotid atherosclerosis and the mechanism underlying its proatherogenic effect. A total of 1749 stroke/MI-free volunteers received carotid ultrasonic examinations for the measurement of intima-medial thickness (IMT) and plaque. The promoter polymorphism rs11066001 was selected because it affects the transcription of BRAP. We found that the GG genotype was associated with a 1.58-fold increased risk for having at least one plaque compared to carrying the A allele (P = 0.021). When subjects were divided by the cutoff value of IMT above the mean plus 1 standard deviation, there was an overrepresentation of the GG genotype in the subjects with thicker IMT (P = 0.004). The expression of BRAP increased significantly when human aortic smooth muscle cells (HASMCs) were treated with lipopolysaccharide (LPS). HASMCs were transfected with small interfering RNA against BRAP or scrambled sequences before treatment with LPS. Knockdown of BRAP led to attenuated HASMC proliferation and reduced secretion of monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) in response to LPS. Downregulation of BRAP did not affect the protein levels of nuclear factor-κB (NF-κB), but prohibited its nuclear translocation. Coimmunoprecipitation experiments confirmed an interaction between BRAP and the two major components of the IKK signalosome, IκBß and IKKß. Collectively, BRAP conferred a risk for carotid plaque and IMT. Inflammatory stimuli upregulated BRAP expression, and BRAP activated inflammatory cascades by regulating NF-κB nuclear translocation.

Sesamin ameliorates oxidative stress and mortality in kainic acid-induced status epilepticus by inhibition of MAPK and COX-2 activation.

BACKGROUND: Kainic acid (KA)-induced status epilepticus (SE) was involved with release of free radicals. Sesamin is a well-known antioxidant from sesame seeds and it scavenges free radicals in several brain injury models. However the neuroprotective mechanism of sesamin to KA-induced seizure has not been studied. METHODS: Rodents (male FVB mice and Sprague-Dawley rats) were fed with sesamin extract (90% of sesamin and 10% sesamolin), 15 mg/kg or 30 mg/kg, for 3 days before KA subcutaneous injection. The effect of sesamin on KA-induced cell injury was also investigated on several cellular pathways including neuronal plasticity (RhoA), neurodegeneration (Caspase-3), and inflammation (COX-2) in PC12 cells and microglial BV-2 cells. RESULTS: Treatment with sesamin extract (30 mg/kg) significantly increased plasma α-tocopherol level 50% and 55.8% from rats without and with KA treatment, respectively. It also decreased malondialdehyde (MDA) from 145% to 117% (p=0.017) and preserved superoxide dismutase from 55% of the vehicle control mice to 81% of sesamin-treated mice, respectively to the normal levels (p=0.013). The treatment significantly decreased the mortality from 22% to 0% in rats. Sesamin was effective to protect PC12 cells and BV-2 cells from KA-injury in a dose-dependent manner. It decreased the release of Ca2+, reactive oxygen species, and MDA from PC12 cells. Western blot analysis revealed that sesamin significantly reduced ERK1/2, p38 mitogen-activated protein kinases, Caspase-3, and COX-2 expression in both cells and RhoA expression in BV-2 cells. Furthermore, Sesamin was able to reduce PGE2 production from both cells under KA-stimulation. CONCLUSIONS: Taken together, it suggests that sesamin could protect KA-induced brain injury through anti-inflammatory and partially antioxidative mechanisms.

The Association of Olfactory Dysfunction With Depression, Cognition, and Disease Severity in Parkinson's Disease.

Background: Non-motor subtypes of Parkinson's disease (PD) include the limbic, cognitive, and brainstem phenotype, which may have different pathological pathways with olfaction. In this work, we aim to clarify the association between olfactory dysfunction, depression, cognition, and disease severity in PD. Methods: A total of 105 PD subjects were included and divided into anosmia and non-anosmic groups, using the University of Pennsylvania Smell Identification Test (UPSIT). All patients were evaluated with the movement disorder society unified Parkinson's disease rating scale (MDS-UPDRS), the Beck depression inventory (BDI)-II, and the Montreal cognitive assessment (MoCA). Results: The BDI-II and UPSIT scores had a trend of reverse correlation without statistical significance (ß-coefficient -0.12, p = 0.232). However, the odds ratio (OR) in anosmia was 2.74 (95% CI 1.01-7.46) for depression and 2.58 (95% CI 1.06-6.29) for cognitive impairment. For the MDS-UPDRS total and Part 3 score, the anosmia had a ß-coefficient of 12.26 (95% CI 5.69-18.82) and 8.07 (95% CI 3.46-12.67), respectively. Neither depression nor cognitive impairment is associated with motor symptoms. Conclusion: More severe olfactory dysfunction in PD is associated with cognitive impairment and greater disease severity. Depression in PD may involve complex pathways, causing relatively weak association with olfactory dysfunction.