Higher fasting glucose is associated with poorer survival in non-diabetic subjects having ischemia with non-obstructive coronary arteries.

Subjects who have ischemia with non-obstructive coronary arteries (INOCA) experience angina pectoris with evidence of myocardial ischemia but without coronary stenosis. Few studies have investigated factors associated with its survival, especially insulin resistance. In this study, subjects with angina pectoris, without known diabetes mellites (DM), and with non-invasive tests showing myocardial ischemia were admitted for coronary angiography (CAG). Those whose CAG did not reveal stenosis and agreed to receive an oral glucose tolerance test (OGTT) 2 weeks after hospital discharge were enrolled for analysis. All-cause mortality was recorded, which served as the outcome of the study. A total of 587 subjects with INOCA, without known DM, and with OGTT data were analyzed. After OGTT and HbA1c tests, 86 subjects (14.7%) were newly diagnosed with DM and 59.8% had pre-DM. The median duration of follow-up was 7.03 years. Thirty-nine subjects died during the follow-up period. The incidence rate of mortality was 9.9 /1000 person-year. Those who died had a higher fasting glucose (101 ± 17 vs. 94 ± 13 mg/dl, p = 0.003) but a lower estimated glomerular filtration rate (eGFR) (54 ± 22 vs. 87 ± 30 ml/min, p < 0.001). In the Cox survival analysis, a higher fasting glucose (hazard ratio 1.053, p = 0.007) was associated with worse mortality for INOCA without DM (N = 501). On the contrary, a higher eGFR (hazard ratio 0.967, p = 0.012) was protective of better survival for non-diabetic INOCA (N = 501). In conclusion, for non-diabetic INOCA, higher fasting glucose was associated with worse mortality and higher eGFR was protective for better survival.

Effects of Periarticular Multimodal Drug Injection on Pain Control, Early Mobilization, and Length of Hospital Stay in Patients Undergoing Total Knee Arthroplasty.

We investigated the effects of periarticular multimodal drug injection (PMDI) on postoperative pain control, patients' mobilization, and length of hospital stay in patients undergoing total knee arthroplasty (TKA). We retrospectively enrolled patients who underwent unilateral TKA between 2019 and 2020. The formula for PMDI included 0.5 mL epinephrine (1 mg/mL), 1 mL ketorolac (30 mg/mL), 0.5 mL morphine (10 mg/mL), and 20 mL bupivacaine hydrochloride (5 mg/mL), mixed with 60 mL normal saline. The outcomes of interest included (1) the amount of patient-controlled anesthesia (PCA) consumption in the first 24 h after the surgery, (2) early mobilization within 24 h after the surgery, and (3) the length of hospital stay. A total of 127 patients were analyzed. Compared with patients who did not receive PMDI, those who received PMDI had lower consumption of PCA in the first 24 h (ß coefficient -29.9, 95% CI -51.9 to -7.9, p = 0.008), higher odds of early mobilization within 24 h (odds ratio 8.263, 95% CI 3.041 to 22.453, p < 0.001), and shorter length of hospital stay (ß coefficient -0.705, 95% CI -1.158 to -0.252, p = 0.003). We suggest that PMDI may be considered for patients undergoing TKA to improve the quality of care and shorten their length of hospital stay.

Relationship between preoperative glucose level and all-cause mortality in patients with osteoporotic vertebral compression fracture who underwent percutaneous vertebroplasty.

To investigate the relationship between preoperative blood glucose levels and long-term all-cause mortality in patients with osteoporotic vertebral compression fractures (OVCF) who underwent percutaneous vertebroplasty (VP). This single-center retrospective study involved a chart review of patients admitted for VP to treat OVCF between 2013 and 2020. Patients with pathological or multiple fractures or those who did not undergo bone mineral density assessment were excluded. All relevant information was collected from electronic medical records. The survival status of all patients was confirmed at the end of March 2021. Cox proportional hazard models with multivariate adjustments were used to examine the effects of blood glucose levels on all-cause mortality. Overall, 131 patients were retrospectively analyzed (mean age: 75.8 ± 9.3 years, male patients: 26.7%) with a median follow-up period of 2.1 years. Preoperative hyperglycemia (hazard ratio: 2.668, 95% confidence interval [CI] 1.064, 6.689; p = 0.036) and glucose levels (hazard ratio: 1.007, 95% CI 1.002-1.012; p = 0.006) were found to be independently associated with a higher risk of all-cause mortality. This correlation remained significant even after adjusting for age and sex, and other factors and comorbidities that might affect outcomes (hazard ratio: 2.708, 95% CI 1.047, 7.003, p = 0.040 and 1.007; 95% CI 1.001, 1.013, p = 0.016, respectively). Furthermore, a history of diabetes mellitus was not a significant factor influencing long-term all-cause mortality. Preoperative glucose levels were found to be independently associated with survival outcomes in patients with OVCF who underwent VP. Conversely, diabetes mellitus was not associated with long-term all-cause mortality. Our findings highlight that preoperative hyperglycemia is a risk factor for long-term mortality in this aging surgical population.

Associations of overweight/obesity with patient-reported outcome measures after oblique lumbar interbody fusion.

Background: Oblique lateral interbody fusion (OLIF) combined with transpedicular screw fixation has been practiced for degenerative spinal diseases of elderly patients for years. However, overweight patients have been shown to have longer operative times and more complications from surgery. The effect on clinical outcome is still uncertified. The objective of this study was to determine is overweight a risk factor to clinical outcome of OLIF combined with transpedicular screw fixation technique. Material and methods: A retrospective study in patients submitted to OLIF combined with transpedicular screw fixation from January 2018 to August 2019 was conducted. VAS score, ODI score and EQ5D were measured before the operation and one year after the operation. Results: A total of 111 patients were included with 48 patients in the non-obese group and 55 patients in the overweight/obese group. There was no significant difference between the two groups in gender, age, smoking history, hypertension, chronic kidney disease and diabetes mellitus. Overweight/obese group has higher BMI (28.4 vs. 22.7, p < 0.001) than non-obese group. There was no difference between the two groups in pre-operative VAS score, ODI score and EQ5D score. However, the healthy weight group improved much more than the overweight score in VAS score, ODI score and EQ5D score. Conclusion: The overweight/obese patient group had clinical outcomes worse than the non-obese group in terms of pain relief and life functions.

Validation of a Prediction Model for Acute Kidney Injury after Cardiac Surgery in a Retrospective Asian Cohort.

Background: The incidence of postoperative acute kidney injury (AKI) is relatively high in some Asian regions. The objective of this study was to examine the performance of an AKI prediction model developed based on data from a White-dominant population in a retrospective Asian cohort of patients undergoing cardiovascular surgery. Methods: We retrospectively identified 549 patients who underwent elective major cardiovascular surgery (coronary artery bypass graft, valve surgery, and aorta surgery), and excluded those who underwent a percutaneous cardiovascular procedure. Patients with a baseline estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 were also excluded. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) definition. Performance of the prediction model for AKI was expressed as area under the receiver operating characteristic curve (AUC). Results: The prediction model had a good predictive accuracy for postoperative AKI (all AUC > 0.92). The AUC of the prediction model in subgroups of age (<65 years and ≥65 years), sex (male and female), hypertension, and diabetes were all >0.85 (all p values < 0.001). Conclusions: The model could be used to predict postoperative AKI in Asian patients undergoing cardiovascular surgery with a baseline eGFR ≥ 60 mL/min/1.73 m2.

Sex Disparity in the Association of Metabolic Syndrome with Cognitive Impairment.

Background/Objectives: Metabolic syndrome (MS) is a constellation of several cardiometabolic risk factors. We investigated sex disparity in the associations between MS and cognitive impairment using cross-sectional data from Taiwan Biobank. Methods: We determined the associations of MS and its five components with cognitive impairment (mini-mental state examination, MMSE < 24) and the five domains of MMSE using logistic regression analyses. Results: A total of 7399 men and 11,546 women were included, and MS was significantly associated with cognitive impairment only in women (adjusted OR 1.48, 95% CI 1.29-1.71, p = 0.001) (p for interaction 0.005). In women, the association with MS was significant in orientation (adjusted OR 1.21, 95% CI 1.07-1.37, p = 0.003), memory (adjusted OR 1.12, 95% CI 1.01-1.25, p = 0.034) and design copying (adjusted OR 1.41, 95% CI 1.23-1.62, p = 0.001) (p value for interaction 0.039, 0.023, and 0.093, respectively). Among the components of MS, a large waist circumference (adjusted OR 1.25, 95% CI 1.08-1.46, p = 0.003), high fasting glucose (adjusted OR 1.16, 95% CI 1.00-1.34, p = 0.046), and low HDL cholesterol (adjusted OR 1.16, 95% CI 1.00-1.34, p = 0.049) were significantly associated with cognitive impairment in women. Conclusions: Our findings suggest that sex has a significant influence on the association between MS and cognitive dysfunction, especially in orientation and memory.

Maintenance Chemotherapy in Patients with Platinum-Sensitive Relapsed Epithelial Ovarian Cancer after Second-Line Chemotherapy.

(1) Background: Our aim was to evaluate the efficacy and adverse effects of maintenance chemotherapy in platinum-sensitive recurrent epithelial ovarian cancer after second-line chemotherapy. (2) Methods: A total of 72 patients from a single institute who had been diagnosed with platinum-sensitive recurrent ovarian cancer and had experienced either complete or partial response after six cycles of second-line chemotherapy were divided into a standard group (n = 31) with six cycles or a maintenance group (n = 41) with more than six cycles. We then compared patient characteristics and survival outcomes between these two groups. (3) Results: In all patients, after primary management for the first recurrence, the maintenance group showed worse survival outcomes. Patients who had not undergone either surgery or radiotherapy were divided into complete response and partial response groups after six cycles of chemotherapy. In patients with partial response, maintenance chemotherapy led to a significant improvement in PFS (median, 3.6 vs. 6.7 months, p = 0.007), but no significant change in in OS. The median cycle number of maintenance chemotherapy was four. (4) Conclusions: Maintenance chemotherapy may still play an important role in patients with platinum-sensitive recurrent ovarian cancer, particularly in selected patient groups.

Hepatitis Flares or Hepatic Decompensation after Discontinuation of Tenofovir Disoproxil Fumarate and Entecavir in Non-Cirrhotic Hepatitis B e Antigen-Negative Patients.

Hepatic events can occur after discontinuing antiviral therapy. We investigated factors associated with hepatitis flares and hepatic decompensation after discontinuing tenofovir disoproxil fumarate (TDF) and entecavir (ETV). Hepatitis flares within 6 months and hepatic decompensation were compared between non-cirrhotic hepatitis B e antigen-negative patients after discontinuing TDF or ETV by using the Cox proportional hazard model. The cumulative rates of hepatitis flare at 6 months after discontinuing ETV and TDF were 2% and 19%, respectively (p < 0.001). The respective rates of hepatic decompensation at 6 months were 0% and 7% (p = 0.009). Higher alanine aminotransferase (ALT) (AASLD criteria) at the end of treatment (EOT) (HR = 4.93; p = 0.001), an off-therapy dynamic change in HBV DNA (rapid rebound of HBV DNA from the nadir, ≥1 log10 IU/mL per month) (HR = 10.7; p < 0.001), and the discontinuation of TDF (HR = 6.44; p = 0.006) were independently associated with hepatitis flares within 6 months. Older age (HR = 1.06; p < 0.001) and an off-therapy dynamic change in HBV DNA (HR = 3.26; p = 0.028) were independently associated with hepatic decompensation after the discontinuation of antiviral therapy. In summary, we demonstrated several factors associated with hepatitis flares and hepatic decompensation after discontinuing antiviral therapy in non-cirrhotic hepatitis B e antigen-negative patients.

Liposomal bupivacaine administration is not superior to traditional periarticular injection for postoperative pain management following total knee arthroplasty: a meta-analysis of randomized controlled trials.

BACKGROUND: Liposomal bupivacaine (LB) is a relatively new formulation that slowly releases bupivacaine to extend its efficacy for 72-96 h. It is inconclusive whether LB offers better efficacy than traditional periarticular injection (TPAI) following total knee arthroplasty (TKA). METHODS: Relevant randomized controlled trials (RCTs) were searched using electronic databases, including PubMed, Cochrane Library, EMBASE, and Web of Science. Review Manager 5.4.1 was used for calculations. RESULTS: Sixteen RCTs were included in this meta-analysis. LB had better effects on morphine consumption equivalents during postoperative 24-48 h than TPAI. No significant difference was observed in pain relief, incidence of nausea and vomiting, or length of hospital stay between the two groups. CONCLUSION: LB administration during TKA is not superior to TPAI. Studies with larger sample size are needed to validate our findings. PROSPERO registration number: CRD42022355094.

Associations of Long-Term Physical Activity Trajectories With All-Cause Mortality in a General Population.

Objectives: We investigated the associations of mean levels of leisure-time physical activity (LTPA) and latent LTPA trajectories with all-cause mortality risk. Methods: Trajectories of LTPA were established using group-based trajectory analysis with a latent class growth model in a population-based cohort between 1996 and 2014. A Cox-proportional hazard model was conducted to examine the associations of LTPA quintiles and LTPA trajectories with all-cause mortality. Results: A total of 21,211 participants (age 18-90 years) were analyzed (median follow-up 16.8 years). The study participants were divided into five groups according to percentiles of LTPA (<20th, 20th-<40th, 40th-<60th, 60th-<80th, ≥80th) and LTPA trajectories (low/stable, medium/stable, increasing, decreasing, and fluctuating), respectively. Participants with a decreasing trajectory did not have a significantly lower risk of all-cause mortality despite having the highest baseline level of LTPA. In contrast, participants with a medium/stable (HR 0.84, 95% CI 0.72-0.98, p = 0.031) or an increasing (HR 0.57, 95% CI 0.33-0.97, p = 0.037) trajectory had a significantly lower risk of all-cause mortality. Conclusion: Promotion of maintaining stable LTPA is beneficial for public health and survival.

Improved Progression-Free Survival Associated with Tumor-Infiltrating Lymphocytes in High-Grade Endometrial Cancer.

Tumor-infiltrating lymphocytes (TILs) have emerged as a prognostic marker in endometrial cancer (EC). However, the role of TILs in EC with distinct histology grades and molecular types (such as mismatch repair [MMR] deficiency) has not yet been made clear. We retrospectively included 237 patients with primary EC who underwent a standard staging operation of laparoscopic or laparotomy total hysterectomy and bilateral salpingo-oophorectomy for analyses. An independent pathologist who was blind to the study patients' information reviewed the pathologic slides to assess TILs according to the method introduced by the International Immuno-Oncology Biomarkers Working Group in 2017. The outcomes of interest included both progression-free survival (PFS) and overall survival (OS). The Kaplan-Meier method was used to determine the curves of PFS and OS according to TILs, and also in the relevant subgroups (low-grade vs. high-grade, MMR-proficient vs. MMR-deficient). After a median follow-up duration of 1.82 years, 18 patients had experienced either disease progression or death. Overall, TILs (+) were not associated with PFS or OS. We did observe, however, that TILs (+) were associated with a better PFS (p = 0.045) in patients with high-grade EC, but not in those with low-grade tumors (p = 0.733). The effect of TILs on PFS was not observed in patients with MMR-proficient (p = 0.347) or MMR-deficient (p = 0.168) EC. TILs were associated with a better PFS in patients with high-grade EC. Our results suggest that TILs may be a potential prognostic marker in these patients.

Correlation of Foraminal Parameters with Patient-Reported Outcomes in Patient with Degenerative Lumbar Foraminal Stenosis.

The relationship between quantitative anatomic parameters in MRI and patient-reported outcomes (PROs) before and after surgery in degenerative lumbar foraminal stenosis remains unknown. We included 58 patients who underwent transforaminal lumbar interbody fusion (TLIF) for single-level degenerative disc disease with foraminal stenosis between February 2013 and June 2020. PROs were evaluated using the visual analog scale (VAS) for back and leg pain, Oswestry Disability Index (ODI), and EuroQol-5D (EQ-5D). The foraminal parameters assessed using preoperative MRI included foraminal height, posterior intervertebral disc height, superior and inferior foraminal width, and foraminal area. The correlation between foraminal parameters and PROs before operation, at 1 year follow-up, and change from baseline were assessed. The associations between the aforementioned parameters were examined using linear regression analysis. The analysis revealed that among these parameters, superior foraminal width was found to be significantly correlated with ODI and EQ-5D at the 1 year follow-up and with change in ODI and EQ-5D from baseline. The associations remained significant after adjustment for confounding factors including age, sex, body mass index, and duration of hospital stay. The results indicated that in degenerative lumbar foraminal stenosis, decreased superior foraminal width was associated with better improvement in disability and quality of life after TLIF.

Risk of all-cause mortality in subjects with varying degrees of renal impairment with or without dietary protein restriction.

BACKGROUND AND OBJECTIVE: Low-protein diet (less than 0.8g/kg/day) has been practiced in the management of chronic kidney disease (estimated glomerular filtration rate [eGFR]<60ml/min/1.73m2 or urine albumin-to-creatinine ratios [UACR] ≥30mg/g) for decades. However, its effect on all-cause mortality is unclear. We investigated the association between a low-protein intake and all-cause mortality in subjects with varying degrees of renal impairment. MATERIALS AND METHODS: We analyzed participants in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2010. They were divided into four groups according to their eGFR (≥60 or <60ml/min/1.73m2) and UACR (≥30 or <30mg/g). Daily protein intake of the NHANES participants could be assessed using information from the dietary interview questionnaires. The mortality data was retrieved by linking to the National Death Index till the end of 2011. The hazard ratios for all-cause mortality were evaluated by the weighted Cox proportional hazards regression models. RESULTS: A total of 8093 participants were analyzed. During a median follow-up of 4.7 years, participants with UACR≥30mg/g (with or without eGFR<60ml/min/1.73m2) had a higher risk of all-cause mortality compared with those having UACR<30mg/g and eGFR≥60ml/min/1.73m2 (reference group). The higher risk of mortality in participants with UACR≥30mg/g was consistently observed in those with or without a low-protein intake. CONCLUSIONS: A low-protein intake was not associated with a lower risk of all-cause mortality in subjects with varying degrees of renal impairment.

Trends in hospitalizations and emergency department visits among women with hyperglycemia in pregnancy between 2008 and 2017 in Taiwan.

Introduction: We investigated health service utilization, including hospitalizations and emergency department visits, for women with hyperglycemia in pregnancy between 2008 and 2017 in Taiwan. Methods: Data from the Health and Welfare Data Science Center were used to conduct this nationwide population-based study. We identified pregnant women and the date of childbirth according to Birth Certificate Applications from 2007 to 2018. The study population was divided into four groups: known DM, newly diagnosed DM, GDM, and no DM/GDM. To assess quality of healthcare during the gestation period, trends in 30-day readmission rate, number of emergency department visits/hospitalizations per 100 childbirths, and length of hospital stay from 2008 to 2017 were examined. Results: A total of 1830511 childbirths and 990569 hospitalizations were identified for analyses. Between 2008 and 2017, women with hyperglycemia in pregnancy (known DM, newly diagnosed DM, and GDM) had a higher rate of hospitalization, a longer length of hospital stay, and higher rates of various maternal and fetal outcomes, compared with women with no DM/GDM. Nevertheless, the differences between women with GDM and those with no DM/GDM in the aforementioned outcome measures were modest. Women with GDM had a modest decrease in the 30-day readmission rate (p for trend 0.046) with no significant difference in the number of emergency department visits during the study period. Discussion: Our findings provide evidence of the quality of healthcare for women with GDM between 2008 and 2017 in Taiwan.

Pre-operative anemia was associated with all-cause mortality in patients with vertebral fracture who underwent percutaneous vertebroplasty.

Purpose: We investigated the association between pre-operative anemia and long-term all-cause mortality in patients with vertebral fracture who underwent a vertebroplasty. Materials and methods: We retrospectively selected patients who were admitted for vertebroplasty for vertebral compression fracture between 2013 and 2020. Patients who had pathologic fractures or had no assessment of bone mineral density were excluded. Relevant information was collected from electronic medical records. Patients' survival status was confirmed at the end of March 2021. Cox-proportional hazard models were conducted to examine the effects of anemia (<12 g/dL vs. ≥12 g/dL) and pre-operative hemoglobin levels (as a continuous variable) on all-cause mortality with multivariate adjustments. Results: A total of 167 patients were analyzed (mean age 75.8 ± 9.3 years, male 25.7%). After a median follow-up duration of 2.1 years, pre-operative anemia (hemoglobin <12 g/dL vs. ≥12 g/dL) was independently associated with a higher risk of all-cause mortality (hazard ratio 2.762, 95% CI 1.184 to 6.442, p = 0.019). An increase in pre-operative hemoglobin was associated with a lower risk of all-cause mortality after multivariate adjustment (hazard ratio 0.775, 95% CI 0.606 to 0.991, p = 0.042). Conclusion: Pre-operative anemia (<12 g/dL) was independently associated with survival outcome among patients with vertebral compression fractures who underwent vertebroplasty. Our findings highlight anemia as a risk factor of long-term mortality in this elderly surgical population.

Association of Body Mass Index with Long-Term All-Cause Mortality in Patients Who Had Undergone a Vertebroplasty for a Vertebral Compression Fracture.

We aimed to investigate the association between preoperative body mass index (BMI) and postoperative long-term mortality in patients who underwent a vertebroplasty. We retrospectively enrolled patients with a vertebral compression fracture who underwent a vertebroplasty between May 2013 and June 2020 in a medical center in Taiwan. The survival status of the study sample was confirmed by the end of March 2021. Cox-proportional hazard models were conducted to examine the effects of being overweight/obese (≥25 kg/m2 vs. <25 kg/m2) and BMI (as a continuous variable) on all-cause mortality after adjusting for age, sex, history of smoking, diabetes, hypertension, chronic kidney disease, and osteoporosis. A total of 164 patients were analyzed (mean age 75.8 ± 9.3 years, male 25.6%, mean BMI 24.0 ± 4.1 kg/m2) after a median follow-up of 785 days. Compared with a BMI < 25 kg/m2, a BMI ≥ 25 kg/m2 was associated with a significantly lower risk of all-cause mortality (HR 0.297, 95% CI 0.101 to 0.878, p = 0.028). These findings were consistent when BMI was examined as a continuous variable (HR 0.874, 95% CI 0.773 to 0.988, p = 0.031). A low BMI (<22 kg/m2) should be considered as a risk factor for postoperative long-term mortality in this ageing population.

Adherence to the dietary approaches to stop hypertension diet and all-cause mortality in patients with a history of heart failure.

Background and aims: We investigated the association of adherence to the Dietary Approaches to Stop Hypertension (DASH) diet with all-cause mortality in patients with a history of heart failure. Methods: We analyzed data from the National Health and Nutrition Examination Survey (NHANES). Dietary information was obtained from a 24-h dietary recall interview. Adherence to the DASH diet was assessed using the DASH score. The primary outcome was all-cause mortality which was confirmed by the end of 2011. Weighted Cox proportional hazards regression models were used to determine the hazard ratios and 95% CI for the association of the DASH score and all-cause mortality with multivariate adjustment. Results: The median DASH score was 2 among the 832 study participants. There were 319 participants who died after a median follow-up duration of 4.7 years. A higher DASH score (>2 vs. ≤ 2) was not associated with a decrease in the risk of all-cause mortality (adjusted HR 1.003, 95% CI 0.760-1.323, p = 0.983). With respect to the components of the DASH score, a lower sodium intake was not associated with a decreased risk of mortality (adjusted HR 1.045, 95% CI 0.738-1.478, p = 0.803). Conclusion: A higher DASH score (>2 vs. ≤ 2) was not associated with all-cause mortality in patients with heart failure.

Associations of insulin resistance and insulin secretion with bone mineral density and osteoporosis in a general population.

We investigated the associations of insulin resistance and ß-cell secretion with bone mineral density (BMD) and osteoporosis using data from the National Health and Nutrition Examination Survey. Data on BMD assessed using dual-energy x-ray absorptiometry from 5292 participants were analyzed. Insulin resistance and ß-cell secretion were assessed using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and ß-cell function (HOMA-ß), respectively. We divided the study population into four groups according to HOMA-IR (<2 vs. ≥ 2) and HOMA-ß (<100 vs. ≥ 100). BMD and T score at the lumbar spine, hip joint, and femur were used for analyses. Osteoporosis was defined as a T score ≤ -2.5. Logistic regression analyses were conducted to examine the associations of HOMA-IR and HOMA-ß with osteoporosis, and the joint effects of HOMA-IR and HOMA-ß on osteoporosis. We found a positive association between HOMA-IR and osteoporosis in participants with a HOMA-ß ≥ 100 (OR 8.773, 95% CI 2.160-35.637, p=0.002 at the femoral neck). A negative association between HOMA-ß and osteoporosis was noted in those with a HOMA-IR <2 (OR 0.183, 95% CI 0.038-0.882, p=0.034 at the femoral neck). Compared with participants who had HOMA-IR <2 and HOMA-ß <100, those with HOMA-IR <2 and HOMA-ß ≥ 100 had a lower risk of osteoporosis (OR 0.126, 95% CI 0.020-0.805, p=0.032 at the femoral neck). In conclusion, the association between HOMA-ß and BMD/osteoporosis changed as HOMA-IR increased. HOMA-ß was negatively associated with osteoporosis when HOMA-IR <2. The association was not significant when HOMA-IR ≥ 2.

Aryl hydrocarbon receptor deficiency augments dysregulated microangiogenesis and diabetic retinopathy.

Diabetic retinopathy (DR) is a pathophysiologic vasculopathic process with obscure mechanisms and limited effective therapeutic strategies. Aryl hydrocarbon receptor (AhR) is an important regulator of xenobiotic metabolism and an environmental sensor. The aim of the present study was to investigate the role of AhR in the development of DR and elucidate the molecular mechanism of its downregulation. DR was evaluated in diabetes-induced retinal injury in wild type and AhR knockout (AhR-/-) mice. Retinal expression of AhR was determined in human donor and mice eyes by immunofluorescence since AhR activity was examined in diabetes. AhR knockout (AhRKO) mice were used to induce diabetes with streptozotocin, high-fat diet, or genetic double knockout with diabetes spontaneous mutation (Leprdb) (DKO; AhR-/-×Leprdb/db) for investigating structural, functional, and metabolic abnormalities in vascular and epithelial retina. Structural molecular docking simulation was used to survey the pharmacologic AhR agonists targeting phosphorylated AhR (Tyr245). Compared to diabetic control mice, diabetic AhRKO mice had aggravated alterations in retinal vasculature that amplified hallmark features of DR like vasopermeability, vascular leakage, inflammation, blood-retinal barrier breakdown, capillary degeneration, and neovascularization. AhR agonists effectively inhibited inflammasome formation and promoted AhR activity in human retinal microvascular endothelial cells and pigment epithelial cells. AhR activity and protein expression was downregulated, resulting in a decrease in DNA promoter binding site of pigment epithelium-derived factor (PEDF) by gene regulation in transcriptional cascade. This was reversed by AhR agonists. Our study identified a novel of DR model that target the protective AhR/PEDF axis can potentially maintain retinal vascular homeostasis, providing opportunities to delay the development of DR.