Enhanced immune capture of extracellular vesicles with gelatin nanoparticles and acoustic mixing.

Extracellular vesicles (EVs) originating from cancer cells incorporate various critical biomolecules that can aid in early cancer diagnosis. However, the rapid analysis of these micro vesicles remains challenging due to their nano-scale size and overlapping dimensions, hindering sufficient capture in terms of quantity and purity. In this study, an acoustofluidic device was developed to enhance the yield of immune-captured EVs. The channel of the device was modified with degradable gelatin nanoparticles (∼220 nm) to increase the surface roughness, and subsequently treated with CD63 antibodies. The acoustic-induced streaming would prolong the rotation time of the EVs in the targeted continuous flow area, improving their aggregation towards the surrounding pillars and subsequent capture by the specific CD63 antibodies. Consequently, the capture efficiency of the device was improved when the signal was on, as evidenced by enhanced fluorescence intensity in the main channel. It is demonstrated that the acoustofluidic device could enhance the immune capture of EVs through acoustic mixing, showcasing great potential in the rapid and fast detection of EVs in liquid biopsy applications.

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.

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.

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.

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.

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.

Aging Characteristics and Ecological Effects of Primary Microplastics in Cosmetic Products Under Different Aging Processes.

Microplastics are becoming an increasingly environmental concern, but only a few studies have focused on primary microplastics. Herein, four primary microplastics (Lapis, Jade, Topaz and White) commonly used in cosmetic products were selected to investigate the effects of sunlight, seawater, and soil aging on their environmental behaviors. After sunlight and seawater aging, the surfaces of all four microplastics developed breaks and cracks, with particle sizes decreased and specific surface areas increased. Topaz exhibited the most significant changes under sunlight and seawater aging and its maximum adsorption capacity of phenanthrene significantly increased by 22.50% and 47.86%, respectively. Under soil aging, amending with either White or Topaz changed the soil bacterial community composition and diversity, but they had less ecological impacts than polyvinyl chloride plastic. The results of this study provide vital information for understanding the aging characteristics, environmental behavior, and ecological effects of primary microplastics under natural aging processes.

Transcription factor GATA1 represses oxidized-low density lipoprotein-induced pyroptosis of human coronary artery endothelial cells.

BACKGROUND: Atherosclerosis (AS) is defined as a chronic inflammatory disorder underly the pathogenesis of cardiovascular diseases (CVDs). Endothelial pyroptosis is associated with AS-like diseases and other CVDs. OBJECTIVE: This work was designed to expound on the effect of GATA-binding protein 1 (GATA1) on pyroptosis of human coronary artery endothelial cells (HCAECs) in AS. METHODS: HCAECs were treated with oxidized-low density lipoprotein (ox-LDL) to establish HCAEC injury models. Plasmids for overexpressing GATA1 or silencing retinoic acid-related orphan receptor α (RORα) were transfected into HCAECs. Thereafter, the mRNA levels of GATA1 and RORα in HCAECs were detected using real-time quantitative polymerase chain reaction. HCAEC viability was examined using the cell counting kit-8 method. The levels of pyroptosis-related proteins NOD-like receptor protein 3 (NLRP3), cleaved-Caspase-1, N-terminal of gasdermin D (GSDMD-N), and pyroptosis-related inflammatory cytokines interleukin (IL)-1ß and IL-18 were determined using Western blot and enzyme-linked immunosorbent assays, respectively. The targeting relationship between GATA1 and RORα was verified using the chromatin-immunoprecipitation assay. Then, the rescue experiment was conducted to explore the effect of RORα on pyroptosis of ox-LDL-treated HCAECs. RESULTS: In ox-LDL-treated HCAECs, GATA1 and RORα expressions were decreased, HCAEC viability was reduced, and the levels of NLRP3, cleaved-Caspase1, GSDMD-N, IL-1ß, and IL-18 were elevated. GATA1 overexpression increased HCAEC viability and attenuated pyroptosis. GATA1 bound to the RORα promoter region to stimulate RORα transcription, and RORα suppression facilitated ox-LDL-induced pyroptosis of HCAECs. CONCLUSIONS: GATA1 activated RORα transcription and therefore limited pyroptosis of ox-LDL-treated HCAECs.

Comparative study of coronary artery bypass grafting combined with off-pump mitral valvuloplasty versus coronary artery bypass grafting alone in patients with moderate ischemic mitral regurgitation.

INTRODUCTION: Whether mitral surgery should be performed simultaneously with coronary artery bypass grafting (CABG) in patients with moderate ischemic mitral regurgitation (MIMR) is controversial. This study was performed to introduce a method of off-pump mitral valvuloplasty after off-pump CABG (OPCABG) and compare it with OPCABG alone. METHODS: Eighty-three patients with MIMR underwent OPCABG. Among them, 21 patients (Group A) underwent posterior mitral annuloplasty without cardiopulmonary bypass, and 62 patients (Group B) underwent OPCABG alone. The primary endpoint of follow-up was the mitral regurgitation area. RESULTS: The mean mitral regurgitant area in Group A and B was 6.42 ± 1.02 and 5.49 ± 1.24 cm2 preoperatively (p = .479), 2.93 ± 1.35 and 3.28 ± 1.93 cm2 at 1 week postoperatively (p = .516), 3.06 ± 2.16 and 3.09 ± 1.85 cm2 at 3 months postoperatively (p = .839), and 3.02 ± 1.60 and 3.7 cm2 (median) at 1 year postoperatively (p = .043). There was less regurgitation in Group A at the mid-term. Intragroup comparison showed significant differences between the preoperative and postoperative values in both groups, with no difference in the regurgitant area at each postoperative time point in Group A but a significant difference between 3 months and 1 year postoperatively in Group B (p = .042). Multiple linear regression showed that the mid-term mitral regurgitant area changes were negatively correlated with graft flow and positively correlated with age. CONCLUSION: In patients with MIMR who underwent OPCABG plus off-pump mitral valve annuloplasty, the mitral regurgitant area was smaller and mitral regurgitation recurrence was less frequent at the mid-term follow-up.

Distal end side-to-side anastomosis of sequential coronary bypass for size mismatched saphenous vein grafts and coronary arteries.

INTRODUCTION: The distal end anastomosis is critical to the entire sequential grafts in coronary artery bypass grafting (CABG), but caliber mismatch diminishes the quality of the anastomosis. We aimed to introduce a modified distal end side-to-side (deSTS) anastomosis to handle the size mismatch and compared with classic distal end end-to-side (deETS) anastomosis. METHODS: From January 2014 to December 2018, 185 patients who underwent off-pump CABG with size mismatched sequential vein grafts (≥3.5 mm) and target coronaries (1.0-1.5 mm) at the distal end anastomoses were included. We retrospectively reviewed the data of the patients, perioperative and follow-up outcomes were analyzed. RESULTS: The deSTS group (n = 67) showed higher anastomotic flow (19.8 ± 8.0 vs 14.9±6.8 mL/min; p < 0.001) and lower pulsatility index (2.7 ± 0.8 vs 3.2 ± 1.0; p = 0.001) than the deETS group (n = 118). Higher incidence of in-hospital myocardial infarction (MI) was found in the deETS group but without significant difference (9.0% vs. 15.3%; p = 0.220). Kaplan-Meier analysis illustrated a relatively lower MI and major adverse cardiovascular and cerebrovascular events (MACCE) incidence in the deSTS group, and the deSTS group was associated with a reduction in long-term death, MI and MACCE in the adjusted Cox regression model. In addition, relatively higher graft patency was found in the deSTS group. CONCLUSIONS: The deSTS anastomosis showed superiority in solving size mismatch in sequential CABG, including better intraoperative flow dynamics, ideal long-term graft patency and reduced the incidence of perioperative and follow-up adverse events especially in MI.

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.

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.

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.

Combined Non-Invasive Prediction and New Biomarkers of Oral and Fecal Microbiota in Patients With Gastric and Colorectal Cancer.

Background: There is no information on the commonality and specificity of oral and fecal microbiota in patients with gastric cancer (GC) and colorectal cancer (CRC). Methods: The high-throughput 16S rRNA gene V4 region sequencing was used to perform bioinformatics analysis of oral, fecal, and tissue microbiota in GC (76 subjects), CRC (53), and healthy controls (HC, 70). Furthermore, we determined the microbial characteristics of each part, constructed and verified three classifiers for GC and CRC, and evaluated curves of receiver operating characteristic and precision-recall with probability of disease. Results: Compared to HC, the microbial richness and diversity of GC and CRC decreased in oral cavity and increased in stool; additionally, these indexes in GC tissue were higher than those in CRC tissue. In GC and CRC patients, Haemophilus, Neisseria, Faecalibacterium, and Romboutsia were significantly reduced compared to the relative abundance value of oral or fecal bacterial genera in the HC group, while the Streptococcus, Gemella, Escherichia-Shigella, and Fusobacterium were significantly increased. The oral and tissue microbiota have similar and abundant shared bacterial networks. The single and combined microbial detection have good AUC values based on POD indices for predicting GC, CRC, and gastrointestinal (GI) cancers (GC and CRC). Conclusion: This study is the first to examine the characteristics of oral, fecal, and tumor microbiota in GC and CRC patients, and the similarities and differences in their microbial changes are reported. These oral or fecal bacteria (Haemophilus, Neisseria, Faecalibacterium, Romboutsia, Streptococcus, Gemella, Escherichia-Shigella, and Fusobacterium) may be involved in tumor evolution as potentially characteristic genera. In addition, both oral and fecal microbial detection may provide a solid theoretical foundation for the non-invasive prediction of these cancers.

A clinical study of genetic testing to guide the dosing of warfarin after heart valve replacement.

OBJECTIVE: To explore the role of genetic testing of VKORC1 and CYP2C9 in determining the dosage of warfarin after aortic valve replacement. METHODS: A total of 172 patients receiving warfarin after aortic valve replacement were divided into a control group (n = 86) and an experimental (n = 86) group based on acceptance of genetic testing. In the experimental group, three loci of VKORC1 and CYP2C9 were tested by polymerase chain reaction-restriction fragment length polymorphism technique, and the initial dose of warfarin was determined based on the genetic testing results and warfarin oral-dose table recommended by U.S. Food and Drug Administration (FDA). In the control group, warfarin (3 mg per night) was used as the initial dose. The international normalized ratio (INR) of each patient was continuously monitored after medication. The percentages of patients meeting the target INR in the two groups at specific time points and at 3-month follow-up after discharge from the hospital were monitored, and the incidence of various adverse events was compared between the groups. RESULTS: Based on the results of genetic testing, 68 patients received 3-4 mg/d (79.1%), 10 patients received 0.5-2 mg/d (11.6%), and eight patients received 5-7 mg/d (9.3%) as the initial dosages of warfarin in the experimental group. The percentages of the patients meeting the target INR on the third and sixth day of postoperative medication were 45.3% and 73.3%, respectively, in the experimental group, and 29.8% and 58.3%, respectively, in the control group. The INR critical values during hospitalization occurred in 2.3% in the experimental group and in 7.1% in the control group, while the percentage of the patients meeting the target INR after 3 months was 86.1% in the experimental group and 83.1% in the control group. CONCLUSION: Genetic testing may guide the selection of the initial dose of warfarin after heart valve replacement to rapidly achieve a stable dose.