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Sudoscan as substitute for quantitative sudomotor axon reflex test in composite autonomic scoring scale and its correlation with composite autonomic symptom scale 31 in type 2 diabetes

ObjectiveThis study aims to evaluate the feasibility of substituting electrochemical skin conductance measurement using SUDOSCAN for sudomotor function testing in the Composite Autonomic Scoring Scale (CASS) and to correlate the results with the Composite Autonomic Symptom Scale 31 (COMPASS 31) among patients with type 2 diabetes mellitus (T2DM). MethodsFifty patients with T2DM underwent cardiovascular autonomic function testing and the SUDOSCAN test and completed the COMPASS 31 questionnaire. We developed a SUDOSCAN-based sudomotor subscore as a substitute for the original sudomotor subscore (based on the quantitative sudomotor axon reflex test [QSART]). The modified CASS score (SUDOSCAN-based sudomotor subscore combined with the adrenergic and cardiovagal subscores) and the original CASS score without suomotor assessment (sum of the adrenergic and cardiovagal subscores) were obtained according to the results of the cardiovascular autonomic function and SUDOSCAN tests. ResultsThe total COMPASS 31 score was significantly correlated with the modified CASS score (p = 0.019 and 0.037 for the raw and weighted scores, respectively) but not with the CASS score without sudomotor assessment. After adding the SUDOSCAN-based sudomotor subscore, the number of patients identified as having diabetic autonomic neuropathy (DAN) increased from 24 (48 %, based on the CASS score without sudomotor assessment) to 35 (70 %, based on the modified CASS score). The modified CASS score enhances the accuracy of assessing autonomic function and improves the diagnosis of diabetic autonomic neuropathy (DAN) among patients with T2DM. In medical settings where QSART is not accessible, SUDOSCAN testing offers a practical and efficient alternative.

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The Utilization of Glucagon-like Peptide 1 Agonists and Risk of Following External Eye Diseases in Type 2 Diabetes Mellitus Individuals: A Population-Based Study.

The glucagon-like peptide 1 (GLP-1) agonist showed anti-hyperglycemic and anti-inflammatory effects, which may retard the risk of external eye disease. The protective effect of GLP-1 agonist and dry eye disease (DED) was found, while the relationship between GLP-1 agonist and other corneal diseases was not clear. Herein, we aim to evaluate the association between the usage of GLP-1 agonists and the development of the following external eye disease in type 2 diabetes mellitus (T2DM) patients. A retrospective cohort study using the National Health Insurance Research Database (NHIRD) of Taiwan was conducted. The T2DM patients were divided into those with GLP-1 treatment and those without GLP-1 treatment and matched with a 1:2 ratio. The main outcomes were the development of dry eye disease (DED), superficial keratitis, and infectious keratitis. The Cox proportional hazard regression was adopted to produce the adjusted hazard ratio (aHR) with a 95% confidence interval (CI) of external eye diseases between groups. There were 115, 54, and 11 episodes of DED, superficial keratitis, and infectious keratitis in the GLP-1 group. Another 280, 168, and 31 events of DED, superficial keratitis, and infectious keratitis were recorded in the control group. The GLP-1 group demonstrated a significantly lower incidence of DED (aHR: 0.853, 95% CI: 0.668-0.989, p = 0.0356) and superficial keratitis (aHR: 0.670, 95% CI: 0.475-0.945, p = 0.0107) compared to the control group. In the subgroup analyses, the correlation of GLP-1 agonist and DED development was more prominent in patients younger than 60 years old (p = 0.0018). In conclusion, the GLP-1 agonist treatments are significantly associated with a lower incidence of subsequent DED and superficial keratitis, while the relationship was not significant between GLP-1 agonist usage and infectious keratitis.

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Open Access
Partial Replacement of Diet with Dehulled Adlay Ameliorates Hepatic Steatosis, Inflammation, Oxidative Stress, and Gut Dysbiosis in Rats with Nonalcoholic Fatty Liver Disease.

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing worldwide, and the average age at NAFLD diagnosis has been decreasing. Although some components of adlay can ameliorate lipid metabolism, oxidative stress, inflammatory response, and gut microbiota, few studies have explored the effects of the dietary intake of intact dehulled adlay on liver diseases. Therefore, in this study, we investigated the effects of the dietary intake of dehulled adlay on NAFLD progression and explored the potential underlying mechanisms. Rats were randomized into a control group; a high-fat, high-sucrose diet (60% total energy derived from fat and 9.4% from sucrose)-induced NAFLD group (N); or a high-fat, high-sucrose diet with dehulled adlay group (received the same amounts of dietary fiber and total energy as did the N group). The experimental duration was 16 weeks. The diet containing dehulled adlay mitigated hepatic fat accumulation, proinflammatory cytokine levels, and oxidative stress by regulating the AMPK-Nrf2-NLRP3 inflammasome pathway and ferroptosis. Additionally, the dietary intake of dehulled adlay modulated the composition of the gut microbiota. In conclusion, a diet containing dehulled adlay may decelerate the progression of NAFLD by ameliorating hepatic steatosis, inflammation, oxidative stress, and gut dysbiosis.

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Open Access
Impact of Previous Conventional Cardiac Surgery on the Clinical Outcomes After Heart Transplantation.

The impact of the type, purpose, and timing of prior surgery on heart transplantation (HT) remains unclear. This study investigated the influence of conventional cardiac surgery (PCCS) on HT outcomes. This study analyzed HTs performed between 1999 and 2019 at a single institution. Patients were categorized into two groups: those with and without PCCS. Short-term outcomes, including post-transplant complications and mortality rates, were evaluated. Cox proportional and Kaplan-Meier survival analyses were used to identify risk factors for mortality and assess long-term survival, respectively. Of 368 patients, 29% had PCCS. Patients with PCCS had a higher incidence of post-transplant complications. The in-hospital and 1year mortality rates were higher in the PCCS group. PCCS and cardiopulmonary bypass time were significant risk factors for 1year mortality (hazard ratios = 2.485 and 1.005, respectively). The long-term survival rates were lower in the PCCS group, particularly in the first year. In sub-analysis, patients with ischemic cardiomyopathy and PCCS had the poorest outcomes. The era of surgery and timing of PCCS in relation to HT did not significantly impact outcomes. In conclusion, PCCS worsen the HT outcomes, especially in patients with ischemic etiology. However, the timing of PCCS and era of HT did not significantly affect this concern.

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Open Access
Consensus recommendations on the use of injectable poly-l-lactic acid in Asian patients.

Injectable poly-L-lactic acid (PLLA) has been proven safe and effective with numerous medical applications for more than 25 years. The product has been approved in over 40 countries and is being used for soft tissue augmentation in the face and certain body parts. With the increased demand for subtle and natural-looking aesthetic treatments in the Asia-Pacific region, there is also a heightened need for consistent preparation and effective treatment methodologies to optimize outcomes for Asian patients. The body of evidence in medical literature, clinical data of presented case reports, and the collective experience of the authors are reflected in these consensus recommendations, which also take under consideration the availability of biostimulators in the Asia-Pacific region. The resulting consensus recommendations include patient selection and assessment, management of treatment expectations, appropriate preparation and storage, proper injection techniques and treatment plans, management of adverse effects, PLLA combination with other facial rejuvenation procedures, and other constructive considerations. In the above consensus recommendations, the authors shared their best practices in accordance with the updated preparation and treatment protocols of PLLA. These recommendations represent the clinical and real-world techniques utilized by authors in providing PLLA treatments for Asian patients.

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Open Access
Effect of Annual Influenza Vaccination on the Risk of Lung Cancer Among Patients With Hypertension: A Population-Based Cohort Study in Taiwan.

Objectives: Lung cancer is a main contributor to all newly diagnosed cancers worldwide. The chemoprotective effect of the influenza vaccine among patients with hypertension remains unclear. Methods: A total of 37,022 patients with hypertension were retrospectively enrolled from the Taiwan National Health Insurance Research Database. These patients were further divided into a vaccinated group (n = 15,697) and an unvaccinated group (n = 21,325). Results: After adjusting for sex, age, comorbidities, medications, level of urbanization and monthly income, vaccinated patients had a significantly lower risk of lung cancer occurrence than unvaccinated patients (adjusted hazard ratio [aHR]: 0.56, 95% confidence interval [CI]: 0.47-0.67). A potential protective effect was observed for both sexes and in the elderly age group. With a greater total number of vaccinations, a potentially greater protective effect was observed (aHR: 0.75, 95% CI 0.60-0.95; aHR: 0.66, 95% CI: 0.53-0.82; aHR: 0.26, 95% CI: 0.19-0.36, after receiving 1, 2-3 and ≥4 vaccinations, respectively). Conclusion: Influenza vaccination was associated with a lower risk of lung cancer among patients with hypertension. The potentially chemoprotective effect appeared to be dose dependent.

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Open Access
Proteomic Analysis Reveals Potential Exosomal Biomarkers in Patients With Sporadic Alzheimer Disease.

Despite substantial progress made in the past decades, the pathogenesis of sporadic Alzheimer disease (sAD) and related biological markers of the disease are still controversially discussed. Cerebrospinal fluid and functional brain imaging markers have been established to support the clinical diagnosis of sAD. Yet, due to the invasiveness of such diagnostics, less burdensome markers have been increasingly investigated in the past years. Among such markers, extracellular vesicles may yield promise in (early) diagnostics and treatment monitoring in sAD. In this pilot study, we collected the blood plasma of 18 patients with sAD and compared the proteome of extracted extracellular vesicles with the proteome of 11 age-matched healthy controls. The resulting proteomes were characterized by Gene Ontology terms and between-group statistics. Ten distinct proteins were found to significantly differ between sAD patients and controls (P<0.05, False Discovery Rate, corrected). These proteins included distinct immunoglobulins, fibronectin, and apolipoproteins. These findings lend further support for exosomal changes in neurodegenerative disorders, and particularly in sAD. Further proteomic research could decisively advance our knowledge of sAD pathophysiology as much as it could foster the development of clinically meaningful biomarkers.

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The Role of Additional Staining in the Assessment of the Peritoneal Regression Grading Score (PRGS) in Peritoneal Metastasis of Gastric Origin.

The Peritoneal Regression Grading Score (PRGS) is a 4-tied histologic regression grading score for determining the response of peritoneal metastasis to chemotherapy. Peritoneal biopsies in every abdominal quadrant are recommended. A positive therapy response is defined as a decreasing or stable mean PRGS between 2 therapy cycles. The added value of periodic acid satin (PAS) and Ber-EP4 staining over HE staining for diagnosing PRGS1 (the absence of vital tumor cells) is unclear. A total of 339 biopsies obtained during 76 laparoscopies in 33 patients with peritoneal metastasis of gastric cancer were analyzed. Biopsies classified as PRGS 1 (no residual tumor, n=95) or indefinite (n=50) were stained with PAS, and remaining indefinite or PRGS1 cases additionally stained with BerEP4. After PAS-staining tumor cells were detected in 28 out of 145 biopsies (19%), the remaining 117 biopsies were immunostained with Ber-EP4. Tumor cells were detected in 22 biopsies (19%). In total, additional staining allowed the detection of residual tumor cells in 50 out of 339 biopsies (15%) and changed the therapy response assessment in 7 out of 33 (21%) patients. In summary, 25% (24 out of 95) of initially tumor-free samples (PRGS1) showed residual tumor cells after additional staining with PAS and/or BerEp4. Immunohistochemistry provided important additional information (the presence of tumor cells) in 22 of all 339 biopsies (11.2%). Further staining reduced the instances of unclear diagnosis from 50 to 0 and changed the therapy response assessment in 7 out of 33 patients (21%). We recommend additional staining in PRGS1 or unclear cases.

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Application of Intestinal Barrier Molecules in the Diagnosis of Acute Cellular Rejection After Intestinal Transplantation.

Diagnosing acute rejection after intestinal transplantation currently heavily relies on histopathological analysis of graft biopsies. However, the invasive risks associated with ileoscopic examination and the inaccessibility for biopsy after ileostomy closure hinder real-time detection of rejection responses. Molecules comprising the intestinal barrier have been identified as physiological and molecular biomarkers for various bowel conditions and systemic diseases. To investigate the potential of barrier function-related molecules in diagnosing rejection after intestinal transplantation, plasma samples were collected longitudinally from transplant recipients. The samples were categorized into "indeterminate for rejection (IND)" and "acute rejection (AR)" groups based on clinical diagnoses at each time point. The longitudinal association between plasma levels of these barrier function-related molecules and acute rejection was analyzed using the generalized estimating equations (GEE) method. Logistic GEE models revealed that plasma levels of claudin-3, occludin, sIgA, and zonulin were independent variables correlated with the clinical diagnosis of acute rejection. The subsequent prediction model demonstrated moderate ability in discriminating between IND and AR samples, with a sensitivity of 76.0%, specificity of 89.2%, and accuracy of 84.6%. In conclusion, monitoring plasma levels of claudin-3, occludin, sIgA, and zonulin shows great potential in aiding the diagnosis of acute rejection after intestinal transplantation.

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Open Access