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Introduction: To investigate the association of blepharitis and ischemic stroke (IS). Methods This retrospective cohort study used population-based data in Taiwan. We identified 424,161 patients with blepharitis between 2008 and 2018. 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 risks of IS compared with the individuals without blepharitis (adjusted hazard ratio 1.32, 95% CI 1.29–1.34, P P for interaction P P

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.

BACKGROUND Coronavirus disease 2019 (COVID-19) has caused more than 640 million deaths worldwide. OBJECTIVE We aimed to investigate the mortality trend of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from its outbreak in late 2019 up to the present. METHODS This cohort study assessed 2 693 458 adults diagnosed with COVID-19 at 48 healthcare organizations (HCOs) in the United States from January 1, 2020, to June 30, 2022. The inclusion criterion was the documentation of the International Classification of Diseases, 10th Revision, Clinical Modification (ICD–10–CM) codes or a positive result of the SARS-CoV-2 laboratory test. RESULTS Four sharp surges in the number of deaths and case fatality rate (CFR) from January 2020 to June 2022 were identified. The highest CFR occurred in January 2021 (0.28%). The mortality trends of both sexes positively correlated with the whole follow-up period. In a subgroup analysis, the CFR was always higher in males than in females. The CFR was age dependent, and older people had a higher CFR. Furthermore, racial disparity during the pandemic was remarkable. Regarding the survival rate at each wave of variants, Kaplan–Meier analysis revealed that Delta had a 1.671-fold cumulative mortality risk (95% confidence interval [Cl], 1.615–1.729) compared with Omicron on day 30. Delta also had a significantly increased mortality risk over Omicron in all age groups, except for ages below 19 years. For ages 0–18 years, mortality risk was highest in the Alpha wave. Death attributed by COVID-19 was age dependent for all age groups. Moreover, the CFR of ages above 80 years was as high as 17.33% across the study period. CONCLUSIONS This study is the first longitudinal study on COVID-19 fatality using the TriNetX dataset, and a comprehensive review of the literature and pivotal events on fatality fluctuations. Results suggest that age and male sex are strong mortality risk factors for COVID-19–infected patients. This study also further ascertained the CFR of each SARS-CoV-2 variant retrospectively. Additionally, nonpharmaceutical interventions seem important in lowering the CFR. CLINICALTRIAL none

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.

Objective To review the clinical experience with on pimp mitral valve repair (MVP) and off-pump coronary artery bypass grafting (OPCABG) for coronary atherosclerotic heart disease (CAD). Methods From April 2017 to March 2018, a total of 32 patients received MVP combined with OPCABG in Beijing Anzhen Hospital. The echocardiographic results before and after the operation were compared and SPSS 20.0 statistical software was used to analyze the clinical data of these patients. Results There were 3.69 grafts per case. Artificial ring forming was performed in 26 cases, quadrangular resection in 4, chordal replacement in 2. No death of these patients occurred in the hospital. Thirty patients were followed up from 6 months to 30 mouths with improved heart function. Heart function was class Ⅰ in 26 and class Ⅱ in 4. The postoperative cardiac ultrasonography for reexaminations indicated that 8 with slight mitral regurgitation, 20 with mild regurgitation and 2 with moderate regurgitation. Patients' cardiac function and size of heart (LVESD, LVEDD and LVEF) were remarkably improved. Conclusions OPCABG and MVP should be performed concomitantly when CAD and mitral insufficiency disease present simultaneously. OPCABG operation at the same time line for the treatment of MVP effect is better. The patients' quality of life could be significantly improved. DOI: 10.11855/j.issn.0577-7402.2020.09.13

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.

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.

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.

The temporal response to off-pump anteroapical aneurysm plication has not been well defined. We have evaluated the long-term clinical and functional results of this technique and compared the efficacy with the patch modeling repair.From March 2005 to May 2010, 163 (115 men and 48 women) consecutive patients were operated on for post-infarction left ventricular aneurysm (LVA), 54 patients underwent patch remodeling (group A) and 109 patients underwent off-pump anteroapical aneurysm plication repair (group B). All patients had simultaneous coronary revascularization, other operative procedures included septoplasty in eight and ablation of ventricular tachycardia in six. Follow-up ranged from 1 to 5 years, short-term and mid-term outcomes, including complications, cardiac function, and mortality, were assessed.Early mortality was 1.8% for all patients (group A 1 death vs. group B 2 deaths, not significant (NS)). Peri-operative support included intraaortic balloon pumping in 16 (9.8%), (group A 6 patients vs. group B 10 patients, NS) and inotropic drugs in 84 (51.5%), (group A 34 vs. group B 50, NS). During a mean follow-up of (3.7±0.8) years, eight patients died, with four due to cardiac-related causes. No patient required transplantation, and two required use of an implantable cardioverter-defibrillator for ventricular tachycardia. Survival at 1 and 5 years was 95% and 86%, respectively. It did not differ significantly between group A and group B. Functional class improved from 2.90 ± 0.59 to 1.65 ± 0.54 among the mid-term survivors (P0.001), with no significant difference between the two groups. Pre-operative risk factors for mortality or poor function were ejection fraction (EF)0.35 (OR = 7.9, 95%CI 1.6 - 40.0); congestive heart failure (CHF) (OR = 4.4, 95%CI 1.0 - 19.0); end-systolic volume index (ESVI)80 ml/m(2) (OR = 3.7, 95%CI 1.0 - 14.0); and advanced age70 years (OR = 2.4, 95%CI 1.0 - 12.0).The technique of off-pump anteroapical aneurysm plication associated with coronary grafting can be performed with low operative mortality, providing good symptomatic relief and long-term survival, and similar results can be achieved with patch modeling repair.

Endothelial progenitor cells (EPCs) are used in vascular tissue engineering and clinic therapy. Some investigators get EPCs from the peripheral blood for clinic treatment, but the number of EPCs is seldom enough. We have developed the cultivation and purification of EPCs from the bone marrow of children with congenital heart disease, to provide enough seed cells for a small calibre vascular tissue engineering study.The 0.5-ml of bone marrow was separated from the sternum bone, and 5-ml of peripheral blood was collected from children with congenital heart diseases who had undergone open thoracic surgery. CD34+ and CD34+/VEGFR+ cells in the bone marrow and peripheral blood were quantified by flow cytometry. CD34+/VEGFR+ cells were defined as EPCs. Mononuclear cells in the bone marrow were isolated by Ficoll(®) density gradient centrifugation and cultured by the EndoCult Liquid Medium Kit(™). Colony forming endothelial cells was detected. Immunohistochemistry staining for Dil-ac-LDL and FITC-UEA-1 confirmed the endothelial lineage of these cells.CD34+ and CD34+/VEGFR+ cells in peripheral blood were (0.07 ± 0.05)% and (0.05 ± 0.02)%, respectively. The number of CD34+ and CD34+/VEGFR+ cells in bone marrow were significantly higher than in blood, (4.41 ± 1.47)% and (0.98 ± 0.65)%, respectively (P0.0001). Many colony forming units formed in the culture. These cells also expressed high levels of Dil-ac-LDL and FITC-UEA-1.This is a novel and feasible approach that can cultivate and purify EPCs from the bone marrow of children with congenital heart disease, and provide seed cells for small calibre vascular tissue engineering.

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.

To evaluate the effect of seeding vascular smooth muscle cells and endothelial cells sequentially on biodegradable scaffold in vitro.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).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 P0.05 or P0.05).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.