Sodium-Glucose Cotransporter 2 Inhibitors Reduce the Risk of Hospitalization for Heart Failure and Amputation Rate Compared With Incretin-Based Therapy in Patients With Diabetic Foot Disease: A Nationwide Population-Based Study.

OBJECTIVE: Major adverse cardiovascular event (MACE) outcomes associated with sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapies remain unclear in patients with type 2 diabetes and newly diagnosed diabetic foot complications (DFCs). This study examined the impact of SGLT2i and GLP-1 RA use on the rates of MACEs and amputations in patients with type 2 diabetes and without cardiovascular disease. METHODS: Data from the Taiwan National Health Insurance Research Database (2004-2017) were analyzed, focusing on patients with type 2 diabetes without previous MACE and newly diagnosed DFCs. The primary outcome was the first MACE occurrence, and the secondary outcomes included MACE components, all-cause mortality, and lower extremity amputation (LEA) rates. RESULTS: SGLT2i users showed a significant decrease in the MACE (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.46-0.88) and hospitalization for heart failure (HR, 0.54; 95% CI, 0.35-0.83) rates compared with dipeptidyl peptidase-4 inhibitor users. The amputation rates were also lower in SGLT2i users without LEA at the first DFC diagnosis (HR, 0.28; 95% CI, 0.10-0.75) and did not increase in those with a history of peripheral artery disease or LEA. No significant differences were observed between dipeptidyl peptidase-4 inhibitor and GLP-1 RA users in terms of the primary or secondary outcomes. CONCLUSION: In patients with type 2 diabetes initially diagnosed with DFC, SGLT2i are effective in significantly reducing the hospitalization for heart failure and MACE rates. SGLT2i lower the amputation rates, especially in patients who have not previously had a LEA, than the dipeptidyl peptidase-4 inhibitor therapy.

Depressive symptoms and daily living dependence in older adults with type 2 diabetes mellitus: the mediating role of positive and negative perceived stress.

BACKGROUND: Higher stress is associated with higher levels of depression and instrumental-activities-of-daily-living (IADL) dependence, and depression is strongly associated with specific IADL disabilities. Accordingly, the aim of this study was to investigate the mediating effect of perceived stress on the association between depression and IADL dependence among older adults with diabetes mellitus (DM). METHODS: We examined baseline data collected from a longitudinal study that recruited 110 patients with DM aged ≥ 65 years from the endocrinology outpatient clinic of a district hospital. The instruments used for our measurement processes comprised a demographic data sheet and Chinese versions of the Perceived Stress Scale (PSS), the short form of the Geriatric Depression Scale (GDS-S), and the Lawton IADL Scale. We assessed the mediating effects of positive perceived stress (PPS) and negative perceived stress (NPS) after controlling for five covariates by using a regression-based model run through the SPSS macro PROCESS. RESULTS: We observed negative correlations between GDS-S scores and PPS and between PPS and IADL dependence; we noted positive correlations between GDS-S scores and NPS and between NPS and IADL dependence (all P < 0.01). The indirect effect is coefficient = 0.12, [95% confidence interval = (0.0, 0.33)], suggesting that PPS achieves a mediating effect between depressive symptoms and IADL dependence. However, the NPS does not achieve a mediating effect in the relationship between depressive symptoms and IADL dependence (coefficient = 0.06, 95% CI = - 0.03, 0.15). CONCLUSIONS: Personal PPS mediates the association between depression and IADL dependence in older adults with DM. This finding suggests that providing patients with psychological education to promote their PPS may help prevent their functional decline.

The association between plasma angiopoietin-like protein 4, glucose and lipid metabolism during pregnancy, placental function, and risk of delivering large-for-gestational-age neonates.

BACKGROUND: Large-for-gestational-age (LGA) neonates have increased risk of adverse pregnancy outcomes and adult metabolic diseases. We aimed to investigate the relationship between plasma angiopoietin-like protein 4 (ANGPTL4), a protein involved in lipid and glucose metabolism during pregnancy, placental function, growth factors, and the risk of LGA. METHODS: We conducted a prospective cohort study and recruited women with singleton pregnancies at the National Taiwan University Hospital between 2013 and 2018. First trimester maternal plasma ANGPTL4 concentrations were measured. RESULTS: Among 353 pregnant women recruited, the LGA group had higher first trimester plasma ANGPTL4 concentrations than the appropriate-for-gestational-age group. Plasma ANGPTL4 was associated with hemoglobin A1c, post-load plasma glucose, plasma triglyceride, plasma free fatty acid concentrations, plasma growth hormone variant (GH-V), and birth weight, but was not associated with cord blood growth factors. After adjusting for age, body mass index, hemoglobin A1c, and plasma triglyceride concentrations, plasma ANGPTL4 concentrations were significantly associated with LGA risk, and its predictive performance, as measured by the area under the receiver operating characteristic curve, outperformed traditional risk factors for LGA. CONCLUSIONS: Plasma ANGPTL4 is associated with glucose and lipid metabolism during pregnancy, plasma GH-V, and birth weight, and is an early biomarker for predicting the risk of LGA.

Aldosterone-to-renin ratio (ARR) as a screening tool for primary aldosteronism (PA).

The aldosterone-to-renin ratio (ARR) is the standard screening test for primary aldosteronism (PA). Because of the poor reproducibility of the ARR, repeat testing is recommended if the result is not compatible with the clinical condition. Various methods to measure renin are used in different hospitals in Taiwan, and the ARR cutoff values also differ among laboratories. The Task Force of Taiwan PA recommend using plasma renin activity (PRA) to calculate ARR instead of direct renin concentration (DRC) unless PRA is unavailable, because PRA is widely used in international guidelines and most studies.

Advanced maternal age-related clustering of metabolic abnormalities is associated with risks of adverse pregnancy outcomes.

AIMS: Advanced maternal age (AMA) is correlated with higher risk of adverse pregnancy outcomes while the pathophysiology remains unclear. Our study aimed to investigate whether AMA is linked to the clustering of metabolic abnormalities, which in turn is associated with an increased risk of adverse pregnancy outcomes. METHOD: A total of 857 pregnant woman were recruited in a prospective cohort at National Taiwan University Hospital, from November 2013 to April 2018. Metabolic abnormalities during pregnancy were defined as following: fasting plasma glucose ≥92 mg/dl, body mass index (BMI) ≥24 kg/m2, plasma high-density lipoprotein cholesterol <50 mg/dl, hyper-triglyceridemia (≥140 mg/dl in the first trimester or ≥220 mg/dl in the second trimester), and blood pressure ≥130/85 mmHg. RESULT: Incidence of large for gestational age (LGA), primary caesarean section (CS), and the presence of any adverse pregnancy outcome increased with age. The advanced-age group tended to have more metabolic abnormalities in both the first and the second trimesters. There was a significant association between the number of metabolic abnormalities in the first and the second trimesters and the incidence of LGA, gestational hypertension or preeclampsia, primary CS, preterm birth, and the presence of any adverse pregnancy outcome, adjusted for maternal age. CONCLUSION: AMA is associated with clustering of metabolic abnormalities during pregnancy, and clustering of metabolic abnormalities is correlated with increased risk of adverse pregnancy outcomes.

Understanding Healthcare Providers' Care for Patients with Medications Treating Opioid Use Disorder in the Emergency Department: A Scoping Review.

BACKGROUND: There is limited research exploring the changing clinical practices among healthcare providers (HPs) care for patients with Emergency Department (ED)-initiated Medication for Opioid Use Disorder (MOUD). METHODS: This scoping review followed the methodological framework of Arksey and O'Malley to map relevant evidence and synthesize the findings. We searched PubMed, EMBASE, CINAHL, Web of Science, and Scopus for related studies from inception through October 12, 2022. Following the application of inclusion and exclusion criteria, 16 studies were included. Subsequently, they were charted and analyzed thematically based on ecological systems theory. RESULTS: The main determinants in the four ecological systems were generated as follows: (1) microsystem: willingness and attitude, professional competence, readiness, and preference; (2) mesosystem: ED clinical practices, departmental factors; (3) exosystem: multidisciplinary approaches, discharge planning, and (4) macrosystem: stigma, health insurance, policy. The findings have implications for HPs and researchers, as insufficient adoption, implementation, and retention of MOUD in the ED affect clinical practices. CONCLUSIONS: Across the four ecological systems, ED-initiated MOUD is shaped by multifaceted determinants. The microsystem underscores pivotal patient-HP trust dynamics, while the mesosystem emphasizes interdepartmental synergies. Exosystemically, resource allocation and standardized training remain paramount. The macrosystem reveals profound effects of stigma, insurance disparities, and evolving policies on treatment access and efficacy. Addressing these interconnected barriers is crucial for optimizing patient outcomes in the context of MOUD.

A 20-year study of autoimmune polyendocrine syndrome type II and III in Taiwan.

Purpose: Autoimmune polyendocrine syndrome (APS) is a rare immune-endocrinopathy characterized by the failure of at least two endocrine organs. Clinical characteristics have mainly been described in the Western population. This study comprehensively analyzed the demographic and clinical manifestations of APS II and APS III in Taiwan. Methods: Patients aged ≥20 years with a diagnosis of APS II or APS III in ten hospitals between 2001 and 2021 were enrolled. The clinical and serological characteristics of the patients were retrospectively reviewed. Results: Among the 187 enrolled patients (45 men and 142 women); only seven (3.7%) had APS II, while the others had APS III. Fifty-five patients developed hyperthyroidism and 44 patients developed hypothyroidism. Men were diagnosed with APS at a younger age than women (16.8 vs 27.8 years old, P = 0.007). Most patients were initially diagnosed with type 1 diabetes mellitus. There was a positive correlation between age at diagnosis and the likelihood of developing thyroid dysfunction. For every year older patients were diagnosed with APS III, the risk of developing hyperthyroidism increased by 3.6% (P = 0.002), and the risk of developing hypothyroidism increased by 3.7% (P = 0.035). Positive anti-parietal cell antibodies (APCA) were associated with a higher risk of anemia in patients with APS III (P < 0.001). Conclusion: This study provides the most comprehensive analysis of APS II and APS III in Asia. The percentage of patients with APS II was significantly lower than in the Western population. A second autoimmune endocrinopathy may develop several years after the first one. APCA examination is valuable when evaluating anemia in patients with APS.

Traits of Patients With Pituitary Tumors in Multiple Endocrine Neoplasia Type 1 and Comparing Different Mutation Status.

CONTEXT: Recent studies suggest that the clinical characteristics and biological behavior of pituitary tumors (PITs) in patients with multiple endocrine neoplasia type 1 (MEN1) may not be as aggressive as previously reported. Increased imaging of the pituitary as recommended by screening guidelines identifies more tumors, potentially at an earlier stage. However, it is unknown if these tumors have different clinical characteristics in different MEN1 mutations. OBJECTIVE: To assess characteristics of patients with MEN1 with and without PITs, and compare among different MEN1 mutations. METHODS: Data of patients with MEN1 in a tertiary referral center from 2010 to 2023 were retrospectively analyzed. RESULTS: Forty-two patients with MEN1 were included. Twenty-four patients had PITs, 3 of which were invasive and managed with transsphenoidal surgery. One PIT enlarged during follow-up. Patients with PITs had a higher median age at MEN1 diagnosis than those without PITs. MEN1 mutations were identified in 57.1% of patients, including 5 novel mutations. In patients with PITs, those with MEN1 mutations (mutation+/PIT+ group) had more additional MEN1-associated tumors than those without (mutation-/PIT+ group). The mutation+/PIT+ group had a higher incidence of adrenal tumors and a lower median age at initial manifestation of MEN1 than the mutation-/PIT+ group. The most common neuroendocrine neoplasm was nonfunctional in the mutation+/PIT+ group and insulin-secreting in the mutation-/PIT+ group. CONCLUSION: This is the first study comparing characteristics of patients with MEN1 with and without PITs harboring different mutations. Patients without MEN1 mutations tended to have less organ involvement and it might be reasonable for them to receive less intensive follow-up.

Custom-designed sensors embedded 3D-printed wearable device for improving the hemodialysis-related vascular dysfunction detection.

BACKGROUND: The increasing prevalence of end-stage renal disease (ESRD) imposes a substantial economic burden on public health-care systems. Hemodialysis (HD) is a pivotal treatment modality for patients with ESRD. However, prolonged use of HD vessels may result in stenosis, thrombosis, and occlusion due to repeated daily punctures. Thus, early detection and prevention of the dysfunction of dialysis routes are crucial. OBJECTIVE: In this study, we designed a wearable device for the early and accurate detection of arteriovenous access (AVA) stenosis in HD patients. METHODS: A personalized three-dimensional (3D) printed wearable device was designed by combining the phonoangiography (PAG) and photoplethysmography (PPG) techniques. The capability of this device to monitor AVA dysfunction before and after percutaneous transluminal angioplasty (PTA) was evaluated. RESULTS: After PTA, the amplitudes of both PAG and PPG signals increased in patients with arteriovenous fistulas and those with arteriovenous grafts; this might be due to increased blood flow. CONCLUSION: Our designed multi-sensor wearable medical device using PAG, PPG, and 3D printing appears suitable for early and accurate detection of AVA stenosis in HD patients.

Taiwan's National Health Insurance at the Emergency Department following the COVID-19 outbreak.

Taiwan's National Health Insurance (NHI) is a widely acclaimed universal healthcare system. In the past few years, particularly following the COVID-19 outbreak, challenges related to maintaining the NHI system have surfaced. Since 2020, NHI has faced a series of challenges, including excessive patient visits to the hospital emergency department, a lack of an effective primary care and referral system, and a high turnover rate of healthcare workers. We review major problems related to Taiwan's NHI, emphasizing input from frontline healthcare workers. We provide recommendations for potential policies addressing the concerns around NHI, for example, strengthening the role of primary care services under the NHI administration, reducing the high turnover rate of healthcare workers, and increase the premium and copayments. We hope that this policy analysis may allow policymakers and scholars to understand both the merits and critical problems related to NHI from the clinical perspective.

Effects of Physical Therapy on Joint Pain, Joint Range of Motion, Joint Health, Strength, and Mobility in Patients With Hemophilia: A Systematic Review and Meta-analysis.

OBJECTIVE: This study investigated the effects of physical therapy, including exercise, manual therapy, and physical agent modality, on joints, muscle strength, and mobility of patients with hemophilia. METHODS: PubMed, Embase, MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus were searched from inception to September 10, 2022. Randomized controlled trials comparing pain, range of motion, and health of joints, as well as muscle strength and mobility (timed up and go test) between physical therapy and control groups were included. RESULTS: Fifteen randomized controlled trials with 595 male patients with hemophilia were included. In comparisons between physical therapy and control groups, physical therapy significantly reduced joint pain (standardized mean difference = -0.87; 95% confidence interval, -1.14 to -0.60), increased joint range of motion (standardized mean difference = 0.24; 95% confidence interval, 0.14-0.35), enhanced joint health (standardized mean difference = -1.08; 95% confidence interval, -1.38 to -0.78), improved muscle strength (standardized mean difference = 1.42; 95% confidence interval, 1.16-1.69), and timed up and go test performance (standardized mean difference = -1.25; 95% confidence interval, -1.89 to -0.60). The comparisons demonstrate moderate to high evidentiary quality grades. CONCLUSIONS: Physical therapy is effective in reducing pain, increasing joint range of motion, enhancing joint health, as well as improving muscle strength and mobility in patients with hemophilia. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Recognize the overall effectiveness of physical therapy for patients with hemophilia; (2) Determine how therapeutic exercise can help improve various outcomes of major joints in these patients; and (3) Appraise that physical therapy is safe and can be implemented in clinical practice for these patients. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s) ™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Cognitive appraisals and coping strategies of registered nurses in the emergency department combating COVID-19: A scoping review.

OBJECTIVE: Explore the relevant evidence about stress-related cognitive appraisal and coping strategies among registered nurses in the emergency department (EDRNs) coping with the COVID-19 pandemic. METHODS: This scoping review followed the methodological framework of Arksey and O'Malley to map relevant evidence and synthesize the findings. We searched PubMed, EMBASE, CINAHL, Web of Science, and Scopus electronic databases for related studies from inception through February 2, 2022. This review further conducted study selection based on the PRISMA flow diagram and applied Lazarus and Folkman's Psychological Stress and Coping Theory to systematically organize, summarize, and report the findings. FINDINGS: Sixteen studies were included for synthesis. Most of the studies showed that the majority of EDRNs were overwhelmed by the COVID-19 pandemic. Depression, triaging distress, physical exhaustion, and intention to leave ED nursing were cited as major threats to their wellness. Additionally, comprehensive training, a modified triage system, a safe workplace, psychological support, promotion of resilience, and accepting responsibility may help EDRNs cope with pandemic-related challenges effectively. CONCLUSION: The long-lasting pandemic has affected the physical and mental health of EDRNs because they have increased their effort to respond to the outbreak with dynamically adjusted strategies. Future research should address a modified triage system, prolonged psychological issues, emergency healthcare quality, and solutions facing EDRNs during the COVID-19 or related future pandemics. CLINICAL RELEVANCE: EDRNs have experienced physical and psychological challenges during the pandemic. The ED administrators need to take action to ensure EDRNs' safety in the workplace, an up-to-date triage system, and mental health of frontline nurses to provide high-quality emergency care for combating COVID-19.

Abundance of Prevotella copri in gut microbiota is inversely related to a healthy diet in patients with type 2 diabetes.

While the gut microbiota is known to be influenced by habitual food intake, this relationship is seldom explored in type 2 diabetes patients. This study aims to investigate the relationship between dietary patterns and gut microbial species abundance in 113 type 2 diabetes patients (mean age, 58 years; body mass index, 29.1; glycohemoglobin [HbA1c], 8.1%). We analyzed the gut microbiota using 16S amplicon sequencing, and all patients were categorized into either the Bacteroides enterotype (57.5%, n = 65) or the Prevotella enterotype (42.5%, n = 48) using the partitioning around medoids clustering algorithm, based on the most representative genera. Patients with the Bacteroides enterotype showed better glycemic control with a 2.71 odds of HbA1c ≤ 7.0% compared to the Prevotella enterotype (95% confidence interval, 1.02-7.87; P, 0.034). Dietary habits and the nutrient composition of all patients were assessed using a validated food frequency questionnaire. It was observed that the amounts of dietary fiber consumed were suboptimal, with an average intake of 16 g per day. Additionally, we extracted four dietary patterns through factor analysis: eating-out, high-sugar foods, fish-vegetable, and fermented foods patterns. Patients with the Bacteroides enterotype had higher scores for the fish-vegetable pattern compared to the Prevotella enterotype (0.17 ± 0.13 versus -0.23 ± 0.09; P, 0.010). We further investigated the relationship between the microbiota and the four dietary patterns and found that only the fish-vegetable dietary pattern scores were correlated with principal coordinate values. A lower pattern score was associated with the accumulated abundance of the 31 significant microbial features. Among these features, Prevotella copri was identified as the most significant by using a random forest model, with an area under the receiver operating characteristic of 0.93 (95% confidence interval, 0.88-0.98). To validate these results, we conducted a custom quantitative polymerase chain reaction assay. This assay confirmed the presence of P. copri (sensitivity, 0.96; specificity, 0.97) in our cohort, with a prevalence of 47.8%, and a mean relative abundance of 21.0% in subjects harboring P. copri. In summary, type 2 diabetes patients with the Prevotella enterotype demonstrated poorer glycemic control and deviations from a healthy dietary pattern. The abundance of P. copri, as a major contributing microbial feature, was associated with the severity in the deficiency in dietary fish and vegetables. Emphasis should be placed on promoting a healthy dietary pattern and understanding the microbial correlations.

Serum vascular adhesion protein-1 is associated with twelve-year risk of incident cancer, cancer mortality, and all-cause mortality: a community-based cohort study.

Background: Vascular adhesion protein-1 (VAP-1), a dual-function glycoprotein, has been reported to play a crucial role in inflammation and tumor progression. We conducted a community-based cohort study to investigate whether serum VAP-1 could be a potential biomarker for predicting incident cancers and mortality. Method: From 2006 to 2018, we enrolled 889 cancer-free subjects at baseline. Serum VAP-1 levels were measured using a time-resolved immunofluorometric assay. Cancer and vital status of the participants were obtained by linking records with the computerized cancer registry and death certificates in Taiwan. Results: During a median follow-up of 11.94 years, 69 subjects developed incident cancers and 66 subjects died, including 29 subjects who died from malignancy. Subjects in the highest tertile of serum VAP-1 had a significantly higher risk of cancer incidence (p=0.0006), cancer mortality (p=0.0001), and all-cause mortality (p=0.0002) than subjects in the other tertiles. The adjusted hazard ratios per one standard deviation increase in serum VAP-1 concentrations were 1.28 for cancer incidence (95% CI=1.01-1.62), 1.60 for cancer mortality (95% CI=1.14-2.23), and 1.38 for all-cause mortality (95% CI=1.09-1.75). The predictive performance of serum VAP-1 was better than that of gender, smoking, body mass index, hypertension, diabetes, and estimated glomerular filtration rate but lower than that of age for cancer incidence, cancer mortality, and all-cause mortality, as evidenced by higher increments in concordance statistics and area under the receiver operating characteristic curve. Conclusion: Serum VAP-1 levels are associated with a 12-year risk of incident cancer, cancer mortality, and all-cause mortality in a general population.

Regimen comprising GLP-1 receptor agonist and basal insulin can decrease the effect of food on glycemic variability compared to a pre-mixed insulin regimen.

BACKGROUND: Increasing evidence suggests that glucagon-like peptide 1 (GLP-1) receptor agonists (RA) can stabilize glycemic variability (GV) and interfere with eating behavior. This study compared the impact of insulin, GLP-1 RA, and dietary components on GV using professional continuous glucose monitoring (CGM). METHODS: Patients with type 2 diabetes underwent CGM before and after switching from a twice-daily pre-mixed insulin treatment regimen to a GLP-1 RA (liraglutide) plus basal insulin regimen. The dietary components were recorded and analyzed by a certified dietitian. The interactions between the medical regimen, GV indices, and nutrient components were analyzed. RESULTS: Sixteen patients with type 2 diabetes were enrolled in this study. No significant differences in the diet components and total calorie intake between the two regimens were found. Under the pre-mixed insulin regimen, for increase in carbohydrate intake ratio, mean amplitude of glucose excursion (MAGE) and standard deviation (SD) increased; in contrast, under the new regimen, for increase in fat intake ratio, MAGE and SD decreased, while when the protein intake ratio increased, the coefficient of variation (CV) decreased. The impact of the food intake ratio on GV indices disappeared under the GLP-1 RA regimen. After switching to the GLP-1 RA regimen, the median MAGE, SD, and CV values decreased significantly. However, the significant difference in GV between the two regimens decreased during the daytime. CONCLUSION: A GLP-1 RA plus basal insulin regimen can stabilize GV better than a regimen of twice-daily pre-mixed insulin, especially in the daytime, and can diminish the effect of food components on GV.

The impact of BRAF targeting agents in advanced anaplastic thyroid cancer: a multi-institutional retrospective study in Taiwan.

Anaplastic thyroid cancer (ATC) is a rare but lethal thyroid cancer. Dabrafenib and trametinib has been the standard treatment for the patients with BRAF mutation based on phase II study. This study aimed to exam the impact of dabrafenib and trametinib in ATC patients. ATC patients treated in three institutes in Taiwan were retrospectively reviewed. The clinical features, BRAF status, and survivals were collected. Multivariate analysis was performed to determine the independent prognostic factors. A total of 44 ATC patients were enrolled in current study. Twelve (50%) out of 24 detected patients had BRAF V600E mutation and eleven received dabrafenib and trametinib treatment. Patients treated with dabrafenib and trametinib had longer overall survival (OS) than the patients without treatment with dabrafenib and trametinib (median OS: 10.4 months vs. 3.3 months, P=0.05). The objective response rate was 81.8% and progress-free survival was 7.4 months. Multivariate analysis identified prior surgery, treatment with dabrafenib and trametinib and metastasis to lung, brain, and bone were significant prognostic factors for OS. The benefit of prior surgery was significant in patients receiving dabrafenib and trametinib (P=0.017) rather than those without dabrafenib and trametinib (P=0.067). The current study provides the real-world evidence that targeted therapy with dabrafenib and trametinib was effective and significantly improved the OS for ATC patients. The role of prior surgery became important in the era of targeted therapy. Future studies should focus on resistance mechanisms and combination with immunotherapy for ATC patients.

Diabetic foot disease in subjects with End-stage renal Disease: A nationwide study over 14 years highlighting an emerging threat.

AIMS: To disclose prevalence, demographic, foot characteristics as well as management and lower-extremity amputations (LEAs) of subjects with end-stage renal disease (ESRD) on diabetic foot diseases (DFDs). METHODS: Data were derived from the Taiwan National Health Insurance Research Database between 2004 and 2017. DFDs were defined as ulcers, infections, or severe peripheral arterial diseases (PADs) in patients with type 2 diabetes. Clinical characteristics were analyzed between subjects with and without ESRD. RESULTS: Subjects with ESRD have increased impacts on the DFD population either from annual prevalence (2.7 % to 10.42 %, P for trend < 0.001), or proportional representation in LEAs (7.91 % to 26.37 %, P < 0.001) over 14 years. The annual trends for major-LEAs rates have decreased in both subjects with and without ESRD (13.67 % to 5.82 % and 3.48 % to 1.47 %, both P < 0.001). Notably, the concomitant increase of endovascular treatments (EVTs) (7.09 % to 29.41 %, P < 0.001) was associated with the decrease of major-LEAs (P for interaction < 0.001) in subjects with ESRD. CONCLUSIONS: As the annual prevalence of subjects with ESRD has increased 3.9-fold over years, they now account for more than 30% of annual major-LEA of the total DFD population. Interdisciplinary team approach and aggressive EVTs might reduce major-LEAs in these patients.

Fallopia Japonica and Prunella vulgaris inhibit myopia progression by suppressing AKT and NFκB mediated inflammatory reactions.

BACKGROUND: The increased global incidence of myopia requires the establishment of therapeutic approaches. This study aimed to investigate the effect of Fallopia Japonica (FJ) and Prunella vulgaris (PV) extract on myopia caused by monocular form deprivation (MFD). METHODS: We used human retinal pigment epithelial cell to study the molecular mechanisms on how FJ extract (FJE) and PV extract (PVE) lowering the inflammation of the eye. The effect of FJE and PVE in MFD induced hamster model and explore the role of inflammation cytokines in myopia. RESULTS: FJE + PVE reduced IL-6, IL-8, and TNF-α expression in RPE cells. Furthermore, FJE and PVE inhibited inflammation by attenuating the phosphorylation of protein kinase B (AKT), and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) pathway. In addition, we report two resveratrol + ursolic acid compounds from FJ and PV and their inhibitory activities against IL-6, IL-8, and TNF-α expression levels in RPE cells treated with IL-6 and TNF-α. FJE, PVE, and FJE + PVE were applied to MFD hamsters and their axial length was measured after 21 days. The axial length showed statistically significant differences between phosphate-buffered saline- and FJE-, PVE-, and FJE + PVE-treated MFD eyes. FJE + PVE suppressed expressions of IL-6, IL-8, and TNF-α. They also inhibited myopia-related transforming growth factor-beta (TGF)-ß1, matrix metalloproteinase (MMP)-2, and NF-κB expression while increasing type I collagen expression. CONCLUSIONS: Overall, these results suggest that FJE + PVE may have a therapeutic effect on myopia and be used as a potential treatment option.

Use of expert consensus to improve the diagnosis and management of type 1 diabetes mellitus.

BACKGROUND: Although type 1 diabetes mellitus (T1DM) is recognized as a catastrophic disease among the different types of diabetes, it is often confusedly diagnosed in clinical practice and difficult in care. The objective of this study is to reach a multidisciplinary consensus for the establishment of clinical recommendations on T1DM to optimize its undoubtedly diagnostic evaluation and transitional care. METHODS: Scientific evidence was reviewed by a committee of researchers, based on which recommendations related to T1DM diagnosis were formulated. A two-round method was conducted to compare the opinions of a panel of 32 specialists (adult endocrinologists [53.1%], pediatric endocrinologists [43.8%], a diabetes educator for child and adolescent [3.1%]) on these issues. RESULTS: The panel reached consensus on two of the six items discussed. The four items on which no consensus was reached were related to autoantibody detection and age of onset. Up to 80% of the panelists favored items related to the glucagon test and diabetic ketoacidosis history for T1DM diagnosis. Consensus regarding transitional care through diabetes educators was established. CONCLUSION: The assessment conducted by experts on T1DM showed a high level of professional agreement regarding the proposed diagnostic and transitional care recommendations. A comprehensive analysis of the latest evidence is warranted for the items on which consensus was not established.

A genome-wide association study for melatonin secretion.

Melatonin exerts a wide range of effects among various tissues and organs. However, there is currently no study to investigate the genetic determinants of melatonin secretion. Here, we conducted a genome-wide association study (GWAS) for melatonin secretion using morning urine 6-hydroxymelatonin sulfate-to-creatinine ratio (UMCR). We initially enrolled 5000 participants from Taiwan Biobank in this study. After excluding individuals that did not have their urine collected in the morning, those who had history of neurological or psychiatric disorder, and those who failed to pass quality control, association of single nucleotide polymorphisms with log-transformed UMCR adjusted for age, sex and principal components of ancestry were analyzed. A second model additionally adjusted for estimated glomerular filtration rate (eGFR). A total of 2373 participants underwent the genome-wide analysis. Five candidate loci associated with log UMCR (P value ranging from 6.83 × 10-7 to 3.44 × 10-6) encompassing ZFHX3, GALNT15, GALNT13, LDLRAD3 and intergenic between SEPP1 and FLJ32255 were identified. Similar results were yielded with further adjustment for eGFR. Interestingly, the identified genes are associated with circadian behavior, neuronal differentiation, motor disorders, anxiety, and neurodegenerative diseases. We conducted the first GWAS for melatonin secretion and identified five candidate genetic loci associated with melatonin level. Replication and functional studies are needed in the future.