RETINAL VASCULAR OCCLUSION AND COVID-19 DIAGNOSIS: A Multicenter Population-Based Study.

BACKGROUND: Several ocular diseases have been reported in patients with coronavirus disease 2019 (COVID-19), especially retinal vascular occlusion. This study aimed to examine the risk of retinal vascular occlusion after COVID-19 diagnosis. METHODS: This retrospective cohort study was based on 46 health care organizations in the United States using the TriNetX network. Individuals who had laboratory confirmation of COVID-19 from January 1, 2020, to December 31, 2021, were included. Multivariate analysis was adjusted on age, sex, race, and comorbidities, and hazard ratio was calculated using the Cox proportional hazard regression model. RESULTS: A total of 1,460,634 paired individuals were enrolled for analysis. Patients with COVID-19 had a significantly higher risk of branch retinal vein occlusion (hazard ratio 1.27, 95% confidence interval [CI] 1.04-1.52) than those without COVID-19. The cumulative incidence rate of branch retinal vein occlusion was also significantly higher in patients with COVID-19 compared with those without COVID-19 (log-rank P = 0.014). Within 12 weeks after COVID-19 diagnosis, the transient effect of central retinal vein occlusion (hazard ratio 1.59, 95% confidence interval 1.15-2.17) and branch retinal vein occlusion (hazard ratio 2.11, 95% confidence interval 1.51-2.95) were observed. CONCLUSION: This large-scale multicenter study demonstrated that retinal vein occlusion may be associated with COVID-19.

The risk assessment of uveitis after COVID-19 diagnosis: A multicenter population-based study.

Reports on uveitis after COVID-19 have been limited. Our objective was to examine the risk of uveitis among COVID-19 patients. This was a retrospective cohort study based on the TriNetX platform. The exposure group was patients with positive laboratory test result for SARS-CoV-2 and the comparison group was those tested negative for COVID-19 throughout the study period. The endpoint is the new diagnoses of uveitis. This study composed of 2 105 424 patients diagnosed with COVID-19 (55.4% female; 62.5% white; mean age at index 40.7 years) and 2 105 424 patients (55.4% female; 62.4% white; mean age at index 40.7 years) who never had COVID-19. There was significantly increased risk of new diagnosis of uveitis since the first month after diagnosis of COVID-19 compared with matched controls (HR: 1.18, 95% CI: 1.03-1.34) up to 24 months (HR: 1.16, 95% CI: 1.09-1.22). Our findings strengthen those previously raised by case series with a larger and multicenter study. We found that uveitis was significantly associated with COVID-19 infection. Our findings reiterate the need for careful investigation as well as increased awareness from ophthalmologists in considering the possibility of COVID-19 in vulnerable patients with new presentation of uveitis.

Genetic Variations of Ionotropic Glutamate Receptor Pathways on Interferon-α-induced Depression in Patients with Hepatitis C Viral Infection.

IMPORTANCE: The most supportive evidence of the inflammation theory of depression is that up to one-third of patients with Hepatitis C virus infection (HCV) develop clinical depressive episodes during interferon-α (IFN-α) therapy. As glutamate-mediated excitotoxicity has been found to be a consequence of excessive inflammation and a pathogenic mechanism of depression, it is plausible to investigate genes on ionotropic glutamate receptor pathways. OBJECTIVE: To identify the at-risk genetic variations on ionotropic glutamate receptor pathways for interferon-α-induced depression. METHOD: We assessed 291 patients with chronic HCV undergoing IFN-α therapy and analyzed the single nucleotide polymorphisms (SNPs) in genes related to ionotropic glutamate receptors in this prospective case-control study. Patients who developed IFN-α-induced depression anytime during the treatment were defined as the case group, while those who did not were defined as the control group. Genomic DNA was extracted from peripheral blood and analyzed by Affymetrix TWB array. Allelic and haplotype association tests were conducted using χ2 tests to assess the difference in allele and haplotype frequencies between cases and controls. Additionally, we performed 5000 permutations to control gene-wide family-wise error rates and create empirical p-values. Stratified analyses were then done to control for confounders and adjust odds ratios for our significant SNPs. We also did an additional stratified analysis to re-assess genes with near-significant SNPs (empirical p-value=0.05-0.10), employing Bonferroni correction with the effective number of independent tests to control gene-wide family-wise error rates. RESULTS: The minor and major allele frequencies of rs7542 (empirical p-value=0.0310) in MAPK3, rs3026685 (empirical p-value=0.0378) in PICK1, rs56005409 (empirical p-value=0.0332) in PRKCA, rs12914792 (empirical p-value=0.0096), rs17245773 (empirical p-value=0.0340) in RASGRF1, and rs78387863 (empirical p-value=0.0086), rs74365480 (empirical p-value=0.0200) in RASGRF2 were found significantly different between cases and controls. Haplotype association tests also revealed one significant haplotype in PRKCA (empirical p-value=0.0200) and one in RASGRF1 (empirical p-value=0.0048). Stratified analyses showed no signs of confounders for most of our significant SNPs, except for rs78387863 in RASGRF2. After a re-assessment of our near-significant genes by stratified analyses, two SNPs in GRIN2B turned significant. CONCLUSIONS: This study provided supportive evidence of the involvement of the RAS/RAF/mitogen-activated protein kinase (MAPK) signaling pathway and glutamate ionotropic receptor AMPA type subunit 2(GluR2) transportation in the pathogenesis of IFN-α-induced depression.

Off-pump anteroapical aneurysm plication following left ventricular postinfarction aneurysm: effect on cardiac function, clinical status and survival.

BACKGROUND: In patients with coronary disease and aneurysm, ventricular reconstruction with revascularization is a surgical option. Details of patient selection and optimal surgical technique are still debated. We report our results with off-pump aneurysm plication after ventricular aneurysm with relative wall thinning. METHODS: We retrospectively reviewed the records of 248 patients who had an operation for postinfarction left ventricular aneurysm. Reconstruction was accomplished by off-pump anteroapical aneurysm plication. The following variables were recorded: preoperative clinical, angiographic and echocardiographic findings and operative procedures. Outcomes were early mortality, long-term survival and poor 5-year result, defined as the need for transplantation or repeated hospitalization for congestive heart failure. Risk factors were pinpointed using the t test and survival curves. Independent risk factors were identified using Cox regression methods. RESULTS: Hospital mortality was low (2.0%). Mean follow-up was 5.8 (standard deviation [SD] 3.8) years. Actuarial survival at 1 and 5 years was 94% and 84%. Among the 232 survivors, 200 were in functional class I or II, and the average increase in ejection fraction was 14.0% (SD 3.1%). As determined by multivariable analysis, factors predicting poor outcome were advanced age, ejection fraction less than 0.35, conicity index less than 1, end-systolic volume index greater than 80 mL/m2, advanced New York Heart Association functional class and congestive heart failure. CONCLUSION: Using wall thinning as a criterion for patient selection, the technique of off-pump anteroapical aneurysm plication can be performed with low operative mortality and provides good symptomatic relief and long-term survival.

Strong association of lumbar disk herniation with diabetes mellitus: a 12-year nationwide retrospective cohort study.

Background: Despite reports on the association between diabetes mellitus (DM) and lumbar disk herniation (LDH), large-scale, nationwide studies exploring this relationship are lacking. We aimed to examine the profiles of DM in individuals with LDH and explore the potential mechanisms underlying the development of these disorders. Methods: This retrospective, population-based study was conducted between 2008 and 2019 using data from the National Health Insurance (NHI) research database in Taiwan. The primary outcome was the date of initial LDH diagnosis, death, withdrawal from the NHI program, or end of the study period. Results: In total, 2,662,930 individuals with and 16,922,546 individuals without DM were included in this study; 719,068 matched pairs were established following propensity score matching (1:1 ratio) for sex, age, comorbidities, smoking, alcohol consumption, antihyperglycemic medications, and index year. The adjusted risk for developing LDH was 2.33-fold (95% confidence interval: 2.29-2.37; P<0.001), age-stratified analysis revealed a significantly greater risk of LDH in every age group, and both males and females were approximately twice as likely to develop LDH in the DM compared with non-DM cohort. Individuals with DM and comorbidities had a significantly higher risk of developing LDH than those without, and the serial models yielded consistent results. Treatment with metformin, sulfonylureas, meglitinides, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, or alpha-glucosidase inhibitors was associated with a more than 4-fold increased risk of LDH in the DM cohort. DM was strongly associated with the long-term development of LDH; over the 12-year follow-up period, the cumulative risk of LDH was significantly higher in patients with than without DM (log-rank P<0.001). Conclusion: DM is associated with an increased risk of LDH, and advanced DM may indicate a higher risk of LDH.

A chronological review of COVID-19 case fatality rate and its secular trend and investigation of all-cause mortality and hospitalization during the Delta and Omicron waves in the United States: a retrospective cohort study.

Introduction: Coronavirus disease 2019 (COVID-19) has caused more than 690 million deaths worldwide. Different results concerning the death rates of the Delta and Omicron variants have been recorded. We aimed to assess the secular trend of case fatality rate (CFR), identify risk factors associated with mortality following COVID-19 diagnosis, and investigate the risks of mortality and hospitalization during Delta and Omicron waves in the United States. Methods: This study assessed 2,857,925 individuals diagnosed with COVID-19 in the United States from January 2020, to June 2022. The inclusion criterion was the presence of COVID-19 diagnostic codes in electronic medical record or a positive laboratory test of the SARS-CoV-2. Statistical analysis was bifurcated into two components, longitudinal analysis and comparative analysis. To assess the discrepancies in hospitalization and mortality rates for COVID-19, we identified the prevailing periods for the Delta and Omicron variants. Results: Longitudinal analysis demonstrated four sharp surges in the number of deaths and CFR. The CFR was persistently higher in males and older age. The CFR of Black and White remained higher than Asians since January 2022. In comparative analysis, the adjusted hazard ratios for all-cause mortality and hospitalization were higher in Delta wave compared to the Omicron wave. Risk of all-cause mortality was found to be greater 14-30 days after a COVID-19 diagnosis, while the likelihood of hospitalization was higher in the first 14 days following a COVID-19 diagnosis in Delta wave compared with Omicron wave. Kaplan-Meier analysis revealed the cumulative probability of mortality was approximately 2-fold on day 30 in Delta than in Omicron cases (log-rank p < 0.001). The mortality risk ratio between the Delta and Omicron variants was 1.671 (95% Cl 1.615-1.729, log-rank p < 0.001). Delta also had a significantly increased mortality risk over Omicron in all age groups. The CFR of people aged above 80 years was extremely high as 17.33%. Conclusion: Male sex and age seemed to be strong and independent risk factors of mortality in COVID-19. The Delta variant appears to cause more hospitalization and death than the Omicron variant.

Risk assessment of retinal vascular occlusion after COVID-19 vaccination.

Coronavirus disease 2019 (COVID-19) vaccines are associated with several ocular manifestations. Emerging evidence has been reported; however, the causality between the two is debatable. We aimed to investigate the risk of retinal vascular occlusion after COVID-19 vaccination. This retrospective cohort study used the TriNetX global network and included individuals vaccinated with COVID-19 vaccines between January 2020 and December 2022. We excluded individuals with a history of retinal vascular occlusion or those who used any systemic medication that could potentially affect blood coagulation prior to vaccination. To compare the risk of retinal vascular occlusion, we employed multivariable-adjusted Cox proportional hazards models after performing a 1:1 propensity score matching between the vaccinated and unvaccinated cohorts. Individuals with COVID-19 vaccination had a higher risk of all forms of retinal vascular occlusion in 2 years after vaccination, with an overall hazard ratio of 2.19 (95% confidence interval 2.00-2.39). The cumulative incidence of retinal vascular occlusion was significantly higher in the vaccinated cohort compared to the unvaccinated cohort, 2 years and 12 weeks after vaccination. The risk of retinal vascular occlusion significantly increased during the first 2 weeks after vaccination and persisted for 12 weeks. Additionally, individuals with first and second dose of BNT162b2 and mRNA-1273 had significantly increased risk of retinal vascular occlusion 2 years following vaccination, while no disparity was detected between brand and dose of vaccines. This large multicenter study strengthens the findings of previous cases. Retinal vascular occlusion may not be a coincidental finding after COVID-19 vaccination.

The risk of ischemic stroke significantly increases in individuals with blepharitis: A population-based study involving 424,161 patients.

INTRODUCTION: To investigate the association of blepharitis and ischemic stroke. METHODS: This nationwide retrospective cohort study used population-based data in Taiwan. Individuals aged 20 and above with diagnosis of blepharitis was included based on electrical medical records. After exclusion of ineligible cases, 424,161 patients were identified between 2008 and 2018. The blepharitis and non-blepharitis cohorts were matched based on sex, age, and comorbidities. Multivariable-adjusted Cox proportional hazards model was adopted to calculate the hazard ratio and 95% confidence interval (CI) between blepharitis and non-blepharitis cohorts. The incidence of ischemic stroke was estimated by Kaplan-Meier analysis. RESULTS: 424,161 pairs of blepharitis cohort and non-blepharitis cohort were 1:1 propensity score matched for statistical analysis. Patients with blepharitis had significantly increased risk of ischemic stroke compared with the individuals without blepharitis (adjusted hazard ratio 1.32, 95% CI 1.29-1.34, P < 0.001). A significantly higher risk of ischemic stroke was observed in blepharitis cohort with a previous diagnosis of cancer than in those without cancer (P for interaction < 0.0001). Kaplan-Meier survival analysis revealed the cumulative incidence of ischemic stroke increased in the blepharitis cohort compared with that in the non-blepharitis cohort in 10 years (log-rank P < 0.001). The follow-up period analysis further indicated 1.41-fold adjusted hazard (95% CI 1.35-1.46, P < 0.001) of ischemic stroke within a year after blepharitis diagnosis. CONCLUSIONS: Patients with blepharitis had an elevated risk of developing ischemic stroke. Early treatment and active surveillance are suggested for patients with chronic blepharitis. Further research is required to determine the casual relationship between blepharitis and ischemic stroke, as well as the underlying mechanism.

Sodium-glucose co-transporter 2 inhibitor add-on therapy for metformin delays diabetic retinopathy progression in diabetes patients: a population-based cohort study.

To investigate how sodium-glucose co-transporter 2 inhibitors (SGLT2is) add-on therapy for metformin affects diabetic retinopathy (DR) progression in patients with type 2 diabetes mellitus (T2DM). This nationwide population-based study conducted from January 1, 2016, to December 31, 2018 involved 3,432,911 adults with T2DM in Taiwan. To adjust for potential confounders, data on sex, age, income, comorbidities, diabetes complication severity index score, staging of kidney disease, anti-diabetic medications, and index year were included. The outcome was DR progression, determined by procedure codes or the addition of ICD-9-CM or ICD-10-CM codes to the medical records of the patients during the study. Sensitivity analyses were performed to validate the findings. The adjusted hazard ratio (aHR) of DR progression was 0.89 for the SGLT2is add-on group, relative to the control group [95% confidence interval (CI) 0.81-0.99, P = 0.026]. The Kaplan-Meier curve of the cumulative incidence rate showed that the cumulative incidence of DR progression was considerably decreased in the SGLT2is cohort (log-rank P = 0.0261). The use of SGLT2is for less than 1 year and 1-2 years were associated with a significant increase in the risk of DR progression (aHR 1.56 and 1.88, respectively); however, the risk markedly reduced if the SGLT2is regimen was used for more than 2 years (aHR 0.41, 95% Cl 0.35-0.48; P < 0.001). The serial sensitivity analysis showed consistent findings. The aHR of DR progression was 0.82 for the SGLT2is cohort relative to the non-SGLT2is cohort based on the fundoscopy or indirect ophthalmoscopy findings within 1 year before the outcome date (95% Cl 0.71-0.95; P = 0.009). Co-administration of metformin and SGLT2is may reduce the risk of DR progression. Short-term use of SGLT2is may markedly increase the risk of DR, whereas prolonged use SGLT2is may significantly decrease it.

Secular Trends in Systemic Sclerosis Mortality in the United States from 1981 to 2020.

BACKGROUND: Systemic sclerosis (SSc) has the highest mortality rate among autoimmune disorders. Individuals with SSc frequently die from complications or infections related to SSc. Nonetheless, the sex-age-period interaction of SSc is complex and remains unclear. The study aims to analyze the secular trend of SSc mortality based on data regarding underlying cause of death (UCD) and multiple causes of death (MCD) and clarify the sex-age interaction with time. METHODS: The multiple-cause mortality statistics provided by the National Center for Health Statistics were used to identify all deaths in the United States from 1981 to 2020 in which SSc was indicated anywhere on the death certificates. The age-standardized mortality rate (ASMR) was determined for both sexes, as well as the variations in these rates. Joinpoint regression analysis was utilized to determine the annual percentage change (APC) of ASMR. RESULTS: A total of 44,672 and 66,259 individuals who died between 1981 and 2020 were identified based on the UCD and MCD data, respectively. According to the UCD data, SSc-related AMSR (SSc-ASMR) of the male and female decedents, respectively, declined from 5.01 and 1.94 in 1981-1990 to 4.77 and 1.32 in 2011-2020, respectively (mortality rate ratio 0.95, 95% confidence interval 0.92-0.98). From 1986 to 1999, the APC of SSc-ASMR in female decedents decreased except for those aged 45-64 years (APC 2.1%, p = 0.002). For MCD analysis, in trend 1, only APC of SSc-ASMR in male decedents aged 45-64 years decreased. The SSc-ASMR of both male and female decedents fell on trend 2 arm. In 2011-2020, the ratio of UCD to MCD increased across all age groups for both sexes compared to 1981-1990. Overall, compared to the male decedents, the SSc-ASMR in female decedents increased significantly before 1999, peaked in 1999, followed by continuous decrease until 2020 according to UCD and MCD statistics. CONCLUSIONS: Over the past four decades, the SSc deaths based on the MCD data were 1.48 times more than the UCD data, and the proportion of UCD over MCD increased over time. The SSc-ASMRs in all the sex-age groups significantly decreased over the past two decades. Notably, the mortality rate ratio of women to men with SSc increased in the past four decades.

The Prevalence of Ocular Extra-Intestinal Manifestations in Adults Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

Patients with inflammatory bowel disease (IBD) have a greater frequency of ocular extra-intestinal manifestations (O-EIMs) than the general population, while Crohn's disease (CD) and ulcerative colitis (UC) have inconsistent prevalence, according to previous studies. This study aimed to examine the prevalence of O-EIMs in CD and UC, respectively. We systemically reviewed O-EIMs and IBD across several online databases. Inclusion criteria are as follows: (1) observational studies examining the association between O-EIMs and IBD, such as cross-sectional, case-control, or cohort studies; (2) human and adult individuals; and (3) with case and control groups consisting of patients with and without O-EIMs, respectively. Patients under the age of 18 or any study on pediatric IBD will be excluded. The prevalence of uveitis in adults was determined by 21 studies comprising 190,941 individuals with IBD, including 62,874 CD and 128,067 UC. The pooled analysis revealed significantly increased odds of uveitis in patients with CD than with UC (pooled odd ratio (OR) 1.603, 95% confidence interval 1.254-2.049). The subgroup analysis revealed that European populations had significantly higher odds of developing uveitis and episcleritis in patients with CD than UC (pooled OR 1.683 and 2.401, respectively). Although O-EIMs may be the prodrome of IBD, no consistent finding was obtained as a result of the high heterogeneity from the two included studies. This meta-analysis indicates the significantly increased odds of uveitis in adults with CD than those with UC. In subgroup analysis, European with CD seemed to have higher odds of uveitis and episcleritis than those with UC. Nonetheless, the link between O-EIMs and IBD remained unclear.

Lifitegrast Ophthalmic Solution 5% Is a Safe and Efficient Eyedrop for Dry Eye Disease: A Systematic Review and Meta-Analysis.

Dry eye disease (DED) is a multifactorial disease that causes ocular discomfort and visual impairment on a damaged ocular surface. Lifitegrast, a novel T-cell integrin antagonist, was approved in the United States in July 2016 as a 5% (50 mg/mL) ophthalmic solution for DED management. Currently, no meta-analysis and systemic review based on relevant studies have been conducted. This study aimed to evaluate the efficacy and safety of lifitegrast in patients with DED. We systematically searched Embase, Medline, PubMed, and Web of Science for randomized controlled trials (RCTs) and nonrandomized studies evaluating lifitegrast effects on symptomatic DED. Then, inferior corneal staining score, total corneal staining score (TCSS), nasal lissamine staining score (NLSS), total lissamine staining score, ocular discomfort score (ODS), eye discomfort score (visual analog scale (VAS) score), eye dryness score (EDS), ocular surface disease index score (OSDI-S), and tear break-up time (TBUT) were assessed. Clinical global impression and safety profiles were also evaluated. The studies were pooled in a random-effects model. We included five RCTs, one case-control study, and four longitudinal or retrospective studies, comprising 3197 participants. In the meta-analysis, lifitegrast was superior to the placebo because it improved TCSS, NLSS, TBUT, ODS, eye discomfort score, EDS, and OSDI-Sin DED. However, lifitegrast showed higher risks for ocular and non-ocular treatment-emergent adverse events (TEAEs) overall or at a mild or moderate level. Nonetheless, its incidence of adverse events slightly differed from that in the placebo, especially instillation site discomforts and dysgeusia, thereby considered safe and tolerable. Claims of withdrawal during follow-up caused by TEAEs were extremely rare. Lifitegrast improves DED, although dysgeusia, installation site pain, and irritation may be a concern for some. Overall, most of the adverse events are tolerable. Lifitegrast can alleviate refractory DED and improves patients' quality of life.

New Proximal Anastomosis Technique for Calcified Ascending Aorta in Coronary Artery Bypass Grafting.

To deal with calcified ascending aorta during coronary artery bypass grafting, we describe an alternative technique to create a clampless proximal anastomosis using a Foley catheter and polypropylene suture. In 30 patients, the number of distal anastomoses averaged 3.1 ± 0.7, and mean time of proximal anastomosis was 18.9 ± 1.3 minutes. Neither early nor late death occurred. Stroke occurred in 2 high-risk patients. At mean 1.6 ± 0.5 years of follow-up, 1 patient sustained recurrent angina, and graft patency was 93%. These favorable outcomes show that this alternative technique is a safe and effective approach to calcified ascending aorta in coronary artery bypass grafting.

Predictive Genetic Variations in the Kynurenine Pathway for Interferon-α-Induced Depression in Patients with Hepatitis C Viral Infection.

Importance: The high incidence of major depressive episodes during interferon-α (IFN-α) therapy is considered the most powerful supportive evidence for the inflammation theory of depression. As the kynurenine pathway plays an important role connecting inflammation and depression, it is plausible to investigate this pathway for predictive genetic markers for IFN-α-induced depression. Methods: In this prospective case-control study, we assessed 291 patients with chronic hepatitis C viral infection taking IFN-α therapy and analyzed the single nucleotide polymorphisms (SNPs) in genes in the kynurenine pathway. Our case group contained patients who developed IFN-α-induced depression during the treatment, and others were defined as the control group. Genomic DNA was extracted from leukocytes in the peripheral blood and analyzed by Affymetrix TWB array. We first tested allelic, dominant, and recessive models on each of our SNPs using Fisher's exact test. We then conducted 5000 gene-wide max(T) permutations based on the best model of each SNP to provide strong gene-wide family-wise error rate control. Finally, we preformed logistic regression for the significant SNPs acquired in previous procedures, with sex and education level as covariates to build predictive models. Additional haplotype analyses were conducted with Haploview 4.2 to investigate the combining effect of multiple significant SNPs within a gene. Results: With sex and education level as covariates, rs8082252 (p = 0.0015, odds ratio = 2.716), rs8082142 (p = 0.0031, odds ratio = 2.499) in arylformamidase (AFMID), and rs12477181 (p = 0.0004, odds ratio = 0.3478) in kynureninase (KYNU) were significant in logistic regression models with dominant modes of inheritance. Haplotype analyses showed the two significant SNPs in AFMID to be in the same haploblock and highly correlated (r2 = 0.99). There were two significant haplotypes (by the sequence of rs8082252, rs8082142): AT (χ2 = 7.734, p = 0.0054) and GC (χ2 = 6.874, p = 0.0087). Conclusions: This study provided supportive evidence of the involvement of the kynurenine pathway in IFN-α-induced depression. SNPs in this pathway were also predictive of this disease.

Human vascular smooth muscle cells and endothelial cells cocultured on polyglycolic acid (70/30) scaffold in tissue engineered vascular graft.

BACKGROUND: Current prosthetic, small diameter vascular grafts showing poor long term patency rates have led to the pursuit of other biological materials. Biomaterials that successfully integrate into surrounding tissue should match not only the mechanical properties of tissues, but also topography. Polyglycolic acid (70/30) has been used as synthetic grafts to determine whether human vascular smooth muscle cells and endothelial cells attach, survive and secrete endothelin and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha). METHODS: Endothelial cells and smooth muscle cells were isolated from adult human great saphenous vein. They were seeded on polyglycolic acid scaffold in vitro separately to grow vascular patch (Groups A and B respectively) and cocultured in vitro to grow into vascular patch (Group C). Smooth muscle cells and endothelial cells were identified by immunohistochemical analysis and growth of cells on polyglycolic acid was investigated using scanning electron microscopy. The levels of endothelin and 6-keto-PGF1alpha in the culturing solutions were examined by radioimmunology to measure endothelial function. RESULTS: Seed smooth muscle cells adhered to polyglycolic acid scaffold and over 28 days grew in the interstices to form a uniform cell distribution throughout the scaffold. Then seed endothelial cells formed a complete endothelial layer on the smooth muscle cells. The levels of endothelin and 6-keto-prostaglandin F1 alpha in the culturing solution were (234 +/- 29) pg/ml and (428 +/- 98) pg/ml respectively in Group C and (196 +/- 30) pg/ml and (346 +/- 120) pg/ml in Group B; both significantly higher than in Groups A and D (blank control group, all P < 0.05). CONCLUSIONS: Cells could be grown successfully on polyglycolic acid and retain functions of secretion. Our next step is to use human saphenous vein smooth muscle cells and endothelial cells to grow tubular vascular grafts in vitro.

[Blood vessel tissue engineering: seeding vascular smooth muscle cells and endothelial cells sequentially on biodegradable scaffold in vitro].

OBJECTIVE: To evaluate the effect of seeding vascular smooth muscle cells and endothelial cells sequentially on biodegradable scaffold in vitro. METHODS: Venous endothelial cells and smooth muscle cells of artery were isolated from the umbilical cord of newborn and cultured in vitro. The cultured arterial smooth muscle cells and cultured endothelial cells were seeded on the polyglycolic acid and polylactide (PLGA) nonwoven mesh as tissue scaffolds respectively (group A and group B). And cultured endothelial cells were seeded on the scaffold already seeded with smooth muscle cells sequentially to construct vascular patch (group C). One month after cultivation the patches of the 3 groups underwent HE staining and microscopic examination and scanning electron microscopy. Immunohistochemistry was used to examine the existence of actin and factor VIII-related antigen, secreted by endothelial cells, in the cells. The levels of endothelin and 6-Keto-PGF1alpha in the culture solution were examined by means of radioimmunology so as to measure the endothelial function. Pure culture solution was used as blank control (group D). RESULTS: Microscopy showed that cells were fused into patch in the group C. HE staining showed that the smooth muscle cells were embedded into the PLGA scaffold and grew in multiple layers covered by a layer of endothelial cells on the surface. The types of cells could be identified by immunohistochemical procedure. The levels of endothelin and 6-Keto-PGF1alpha in the culture solution were 229 pg/ml +/- 34 pg/ml and 402 pg/ml +/- 108 pg/ml respectively in the group C, and 200 pg/ml +/- 31 pg/ml and 336 pg/ml +/- 121 pg/ml in the group B, both significantly higher than those in the groups A and D (blank control group, all P < 0.05 or P < 0.05). CONCLUSION: Tissue engineering blood vessel with normal morphological and functional characters to a certain degree can be constructed through seeding cultured vascular smooth muscle cells and endothelial cells sequentially on PLGA scaffold.