Disease Clinical Outcome Research Articles

Sex-differences in the clinical features, managements and outcomes of early-onset atherosclerotic coronary artery disease in China

Abstract Background/Introduction There is an alarming rise in the incidence of atherosclerotic coronary artery disease (CAD) among young adults, particularly in young women. Sex disparities of early-onset CAD in the context of contemporary cardiovascular practice are not well understood. Purpose We aimed to delineate the differences in clinical profiles and prognosis between young men and women with established early-onset CAD. Methods This is a nationwide, hospital-based, longitudinal prospective cohort study. Young patients (aged ≥18 years and ≤ 45 years) with angiographically confirmed severe atherosclerotic obstructive coronary arteries (luminal narrowing ≥ 70%) were included from 38 hospitals across China between May 2017 and May 2020. Coronary risk factors, clinical features and treatments were compared between men and women at baseline. Participants were followed for 3 years. The outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, non-fatal myocardial infarction (MI), unplanned revascularization, and ischemic stroke. The Cox regression analyses were used to estimate hazard ratios (HR) with 95% confidence intervals (CIs) for outcome. Results There were 1524 patients (female: 4.4%) included in this study. The female patients were older than the male patients (41.1±4.0 years for females vs. 39.6±4.4 years for males, p=0.006). They showed a lower prevalence of hypertension, lipid disorders, and smoking or drinking (all p<0.01). The female patients were less likely to have at least 1 modifiable risk factors (female: n=45 (67.2%) vs. male: n=1382 [94.6 %], p<0.001); they showed more favorable laboratory results at baseline, including lipids, serum creatinine and uric acid (all p<0.05) as compared to male patients. Besides, young females presented more often with stable angina on admission, whereas young males tended to present with acute MI (p<0.001). There was no significant sex difference in Gensini Score (p=0.15). Female patients were less likely to undergo revascularization procedures than male patients (73.1% vs. 85.3%, p=0.01). During the 3 years of follow-up, female patients were at a significantly higher risk of MACE compared to their male counterparts (13.4% vs. 5.8%, adjusted HR: 3.07, 95% CI:1.36–6.94, p=0.007) after adjusting for age, smoking, drinking, body mass index, hypertension, diabetes, dyslipidemia, diagnosis and revascularization. Conclusions Distinct sex disparities, unfavorable to young females, were documented among patients with early-onset CAD, with the largest gaps noted in the treatment and prognosis. Despite more favorable baseline profiles, young female patients had insufficient care and 3-fold greater risk for MACE compared to young males. These results highlight the need for strengthening the treatment strategies for this vulnerable disease entity.Figure 1

Utilizing unsupervised machine learning to uncover novel phenogroups within the broad QRS complex

Abstract Background Conduction disease can manifest as a broad QRS complex on the ECG. Broad QRS is conventionally categorised as left bundle branch block (LBBB) and right bundle branch block (RBBB) or non-specific intraventricular conduction delay (IVCD), based on QRS morphology. These subgroups were coined over a century ago and have been relevant for heart failure with reduced ejection fraction and cardiac resynchronization therapy (CRT). However, there may be more precise phenogroups underlying broad QRS complexes. Purpose Using unsupervised machine learning to define novel broad QRS phenogroups and characterise them using clinical variables and disease outcomes. Methods We extracted 51 relevant features using a Variational Autoencoder from 47,456 median-beat ECGs with broad QRS intervals (QRS ≥ 130ms) from a secondary care cohort. These were input into Discriminative Dimensionality Reduction via Learning a Tree (DDRTree), a clustering method that models the continuum of heterogeneity by projecting the underlying distribution as a tree structure in a low-dimensional space, while assigning distinct branch/cluster labels. Results Six distinct phenogroups were identified within broad QRS morphologies (Figure-1). Two branches were RBBB dominant (Branch 1: more males, high-comorbidity; Branch 6: low-comorbidity/healthy-RBBB). Two branches were LBBB dominant (Branch 4: mixed IVCD with CHB burden; Branch 5: more females, CRT responders). Two branches were IVCD/mixed-phenotype (Branch 2: IVCD-dominant, high risk of future cardiovascular events; Branch 3: average/core branch). Within LBBB, Branch 4 and 5 showed similar trends with improving echocardiography profiles and CRT response when adjusted for covariates, each compared against the core branch. Branch 5 was distinct due its high risk of future HF (HR 1.19 [1.07-1.33] p < 0.01), cardiovascular death (HR 1.35 [1.20-1.50] p < 0.0001), all-cause mortality (HR 1.08 [1.01-1.16] p < 0.05) and CHB (HR 1.35 [1.16-1.56] p < 0.0001) (Figure-2). Conversely within RBBB, Branch 1 and 6 showed stark differences across various traits. Branch 1 captured a high-risk profile associated to higher risk of cardiovascular death (HR 1.37 [1.24-1.52] p < 0.0001), all-cause mortality (HR 1.20 [1.12-1.29] p < 0.0001) and CHB (HR 1.15 [1.01-1.32] p < 0.05) (Figure-2), while Branch 6 retained a low-risk phenotype. The tree dimensions also revealed relevant trends in cardiac anatomy and valvular dysfunction; the top-left region in Figure-1 associated with higher left ventricular ejection fraction and lower left ventricular end-diastolic dimension, lower left ventricular end-systolic dimension and a greater CRT response. Conclusion Through unsupervised methods we have identified conduction disease phenogroups with additive value for disease prognosis and CRT response prediction beyond traditional LBBB and RBBB labels. These novel phenogroups may help guide precision care for patients with a broad QRS complex.Figure-1Figure-2

Impact of age on clinical characteristics and 1-year outcomes of non-disabling ischemic cerebrovascular events: A multicenter prospective cohort study

BackgroundThe exploration of age-related clinical features and adverse outcomes of non-disabling ischemic cerebrovascular disease (NICE) has been largely unaddressed in current research. This study aimed to analyze the differences in clinical characteristics and prognostic outcomes of NICE across various age groups, utilizing data from the Xi’an Stroke Registry Study in China.MethodsThe age distribution of NICE was categorized into four groups: age ≤ 54 years, age 55–64 years, age 65–74 years, and age ≥ 75 years. Multivariate Cox logistic regression analysis was employed to evaluate the 1-year risk of outcome events in each age group of patients with NICE. A subgroup analysis was conducted to explore interaction factors influencing age-dependent outcomes in patients with NICE.ResultsThis study included 1,121 patients with NICE aged between 23 and 96 years, with an average age of 63.7 ± 12.2 years. Patients aged ≥ 75 years had a higher proportion of women, lower education levels, and a greater likelihood of having urban employee medical insurance. Those aged < 55 years had a higher prevalence of smoking, while individuals aged > 65 years showed a higher prevalence of comorbidities. Furthermore, there was a significant decrease in body mass index among patients aged ≥ 75 years. Laboratory tests indicated well-controlled blood lipids, liver function, and inflammation across all age groups, but renal function was notably reduced in patients with NICE aged ≥ 75 years. Adjusting for potential confounding factors revealed a significant increase in the one-year risk of all-cause mortality and poor prognosis among patients aged ≥ 75 years compared to those aged < 55 years, with no significant gender difference observed. Subgroup analysis indicated that patients with NICE who consumed alcohol were more prone to experience all-cause mortality with advancing age.ConclusionsAge significantly influences the clinical characteristics and prognostic outcomes of NICE patients. Clinicians should consider age-specific characteristics when diagnosing, treating, and developing prevention strategies. Tailored prevention and treatment strategies for different age groups can enhance prognosis and reduce adverse outcomes in NICE patients.

Long term outcome of Immunoglobulin M (IgM) Nephropathy of Children in National Institute of Kidney Diseases &amp; Urology (NIKDU), Dhaka, Bangladesh

Background: Immunoglobulin M nephropathy (IgMN) is a new clinicoimmunopathologic entity which present mainly as idiopathic nephrotic syndrome in both children and adults. The clinical manifestation of IgMN are highly variable presenting with isolated haematuria or asymptomatic proteinuria. About 6 to 23 percent of IgMN patient developed end stage kidney disease. Usually treated with immunosuppressive agents (cyclosporine/tacrolimus) along with corticosteroid has response rates up to 50%. In our institute last few years we have observed a surprisingly rise of IgM nephropathy in children. Objective: To see the response of IgMN children treated with tacrolimus or mycophenolate mofetil(MMF) and long term follow up to observe their outcome. Methodology : This was a prospective observational study done in the Department of Paediatric Nephrology, National Institute of Kidney Diseases &amp; Urology, Dhaka, starting from January/2014 to December/2017. The study population consists of 86 IgMN children, age ranges from 2 to 12 years. The study was approved by institutional ethical review committee and informed written consent was taken from every parents. Twenty seven patients(Group-I) were selected purposively and treated with MMF and 59 patients (Group- II) treated with tacrolimus for 2 years. Patients were followed up three monthly onward in a prescribed form including adverse effect of drugs. Clinical outcome data like remission, active disease, active disease with renal impairment and dependency on renal replacement therapy(RRT) were documented for statistical analysis. Results: Of 86 IgMN children most of them were older than &gt;8-12 years in both groups and the highest percentage were clinically diagnosed as frequently relapsing nephrotic syndrome. In Group I 43.48% children remain on remission, 13.04% have active disease, 30.43% are active disease with impaired renal function and 4.35 % went into RRT. In Group II 55.56% children remain on remission, 12.96 % have active disease, 16.67% are active disease with impaired renal function and 5.56% dependent on RRT. Conclusion: From above observations, the overall prognosis of IgMN children is not good. The clinical course and disease outcome did not differ significantly between two groups treated with mycophenolate mofetil and tacrolimus. BANGLADESH J CHILD HEALTH 2023; VOL 47 (1) : 34-38

Cipaglucosidase alfa plus miglustat: linking mechanism of action to clinical outcomes in late-onset Pompe disease

Enzyme replacement therapy (ERT) is the only approved disease-modifying treatment modality for Pompe disease, a rare, inherited metabolic disorder caused by a deficiency in the acid α-glucosidase (GAA) enzyme that catabolizes lysosomal glycogen. First-generation recombinant human GAA (rhGAA) ERT (alglucosidase alfa) can slow the progressive muscle degeneration characteristic of the disease. Still, most patients experience diminished efficacy over time, possibly because of poor uptake into target tissues. Next-generation ERTs aim to address this problem by increasing bis-phosphorylated high mannose (bis-M6P) N-glycans on rhGAA as these moieties have sufficiently high receptor binding affinity at the resultant low interstitial enzyme concentrations after dosing to drive uptake by the cation-independent mannose 6-phosphate receptor on target cells. However, some approaches introduce bis-M6P onto rhGAA via non-natural linkages that cannot be hydrolyzed by natural human enzymes and thus inhibit the endolysosomal glycan trimming necessary for complete enzyme activation after cell uptake. Furthermore, all rhGAA ERTs face potential inactivation during intravenous delivery (and subsequent non-productive clearance) as GAA is an acid hydrolase that is rapidly denatured in the near-neutral pH of the blood. One new therapy, cipaglucosidase alfa plus miglustat, is hypothesized to address these challenges by combining an enzyme enriched with naturally occurring bis-M6P N-glycans with a small-molecule stabilizer. Here, we investigate this hypothesis by analyzing published and new data related to the mechanism of action of the enzyme and stabilizer molecule. Based on an extensive collection of in vitro, preclinical, and clinical data, we conclude that cipaglucosidase alfa plus miglustat successfully addresses each of these challenges to offer meaningful advantages in terms of pharmacokinetic exposure, target-cell uptake, endolysosomal processing, and clinical benefit.

Association between clinician team segregation, receipt of cardiovascular care and outcomes in valvular heart diseases.

Racial disparities exist in clinical outcomes for valvular heart disease (VHD). It is unknown whether clinician segregation contributes to these disparities. Among an adequately insured population, we evaluated the relationship between clinician segregation in a hospital and receipt of care by a cardiologist according to patient race. We also evaluated the association between clinician segregation, race and care by a cardiologist on 30-day readmission and 1-year survival. Using Optum's Clinformatics® Data Mart Database (CDM, US commercial and Medicare beneficiaries) from 2010 to 2018, we identified patients with a primary diagnosis of VHD. Hospitals were categorized into low, medium and high segregation groups (SG), according to clinician segregation index (SI). SI can range from 0-1 (0: the ratio of Black to White patients is the same for all clinicians; 1: each clinician treats only Black or only White patients). Outcomes were analysed using generalized linear mixed effect models. Among 8649 patients [median age 75 (67-82), 45.4% female, 16.1% Black, 83.9% White], odds of care from a cardiologist did not vary across race for all SGs [Low SG adjusted odds ratio (aOR): 0.79 (95% CI: 0.58-1.08), P=0.14; Medium SG aOR: 0.86 (95% CI: 0.60-1.25), P=0.43; High SG aOR: 1.07 (95% CI: 0.68-1.69), P=0.76]. Among those that received care from a cardiologist, there was no difference in the 30-day readmission between Black and White patients across SGs [Low SG aOR: 1.05 (95% CI: 0.83-1.31), P=0.70; Medium SG aOR: 1.22 (95% CI: 0.92-1.61), P=0.17; High SG aOR: 0.81 (95% CI: 0.57-1.17), P=0.27]. Among patients that did not receive care from a cardiologist, Black patients in low SG had higher odds of 30-day readmission compared to White patients [aOR: 2.74 (95%CI:1.38-5.43), P<0.01]. Odds of 1-year survival were similar across race for all SG irrespective of receipt of care from a cardiologist [seen by a cardiologist: Low SG aOR: 1.13 (95% CI: 0.86-1.48), P=0.38; Medium SG aOR: 0.83 (95% CI: 0.59-1.17), P=0.29; High SG aOR: 1.01 (95% CI: 0.66-1.52), P=0.98; not seen by a cardiologist: Low SG aOR: 0.56 (95% CI: 0.23-1.34), P=0.19; Medium SG aOR: 0.81 (95% CI: 0.28-2.37), P=0.70; High SG aOR: 0.63 (95% CI: 0.23-1.74), P=0.37]. Among an insured population, race was not associated with care by a cardiologist for VHD or survival. Black patients not seen by cardiologists had higher odds of 30-day readmission in low clinician SG.

Baseline characteristics of Ghanaian children and adults enrolled in PIVOT, a randomised clinical trial of hydroxyurea in HbSC disease in sub-Saharan Africa.

HbSC disease is a common form of sickle cell disease with significant morbidity and early mortality. Whether hydroxyurea is beneficial for HbSC disease is unknown. Prospective Identification of Variables as Outcomes for Treatment (PIVOT, Trial ID PACTR202108893981080) is a double-blind, randomised, placebo-controlled phase II trial of hydroxyurea for people with HbSC, age 5-50 years, in Ghana. After screening, participants were randomised to placebo (standard of care) or hydroxyurea. The primary outcome is the cumulative incidence of haematological toxicities during 12 months of blinded treatment; secondary outcomes include multiple laboratory and clinical assessments. Between April 2022 and June 2023, 112 children and 102 adults were randomised, including 44% females and average age 21.6 ± 14.5 years. Participants had substantial morbidity including previous hospitalisations (93%), vaso-occlusive events (86%), malaria (79%), often received transfusions (20%), with baseline haemoglobin 11.0 ± 1.2 g/dL and foetal haemoglobin 1.8% ± 1.5%. The spleen was palpable in six children and one adult, and ultrasonographic volumes were collected. Proliferative sickle retinopathy was common (30% children, 75% adults), but proteinuria was less common (3% children, 8% adults). Whole blood viscosity, ektacytometry, point-of-sickling, transcranial Doppler, near-infrared spectrometry (NIRS), 6-minute walk, and quality of life were also measured. Now fully enrolled, PIVOT will document the safety and potential benefits of hydroxyurea on clinical and laboratory outcomes in HbSC disease.

Disease progression for histologic diagnosis of metabolic dysfunction-associated steatotic liver disease in the real-world - a nationwide U.S. study.

We compared clinical characteristics and outcomes in real-world metabolic dysfunction-associated steatotic liver disease (MASLD) patients with or without liver biopsy using a nationwide cohort in United States (US) to fill in gaps in selection of biopsy patients. We conducted a retrospective cohort study of adult MASLD patients using Marketscan® Databases (1/2007-12/2021). Patients were categorized into those with or without liver biopsy during follow-up. We analyzed 540,326 MASLD patients: 23,732 with and 516,594 without biopsy. Only 4% of MASLD patients received liver biopsy and biopsy rate decreased in the last 5 years (9.4% to 3.6%). After 1:5 propensity score matching on baseline characteristics including age, sex, and comorbidities, a total of 23,731 patients with biopsy and 118,396 matched patients without biopsy were analyzed. The incidence per 1,000 person-years for hepatocellular carcinoma (HCC) were 0.22 vs. 2.18, cirrhosis 29.75 vs. 90.44 and hepatic decompensation 15.84 vs. 28.25 compared patients with and without biopsy. In multivariable analysis, patients with biopsy had more than 9 times higher risk of developing HCC, 3 times higher risk of cirrhosis, and 78% higher risk of hepatic decompensation. In subgroup analysis, the association remained consistent when stratified by age (&lt;50 and ≥50), sex, and diabetes mellitus. Predictors of having biopsy included age, metabolic disease, and living in North central or Northeast of US. These data can inform clinical patient management that biopsy patients likely represent a selected group at higher risk for disease progression, especially in clinical trials for MASLD therapies.

The Expression of miR-211-5p in Sentinel Lymph Node Metastases of Malignant Melanoma Is a Potential Marker for Poor Prognosis

Metastatic primary cutaneous melanoma is a frequently fatal disease despite recent therapeutic advances. Biomarkers to stratify patients’ prognosis are lacking. MicroRNAs (miRNAs) are small, non-coding RNAs. We aimed to determine the expression of miR-211-5p in primary tumors and metastases of malignant melanoma and its potential use as a prognostic biomarker. We performed in situ hybridization for miRNA-211-5p on 109 FFPE melanoma samples from 76 patients, including 31 paired primary tumor/metastasis samples. For validation, we performed in silico analyses of TCGA skin cutaneous melanoma (SKCM) cohort. High miR-211-5p expression was more frequent in primary tumors (70.8%) compared to metastases (39.3%). In metastases, it was associated with a significantly worse overall survival. Data from TCGA SKCM cohort confirmed that high miR-211-5p expression in melanoma metastases, but not primary tumors, is associated with worse overall survival. MiR-211-5p expression in metastases is associated with a shorter survival, emphasizing the potential of miR-211-5p as a risk predictor for a less favorable clinical outcome in metastatic disease. In situ hybridization could be implemented in a routine laboratory workflow and can be performed on diagnostic tissue.

B-251 Comprehensive Proteomics Analysis Reveals an Exosomal Biomarker Signature Useful for Detection of Non-Small Cell Lung Cancer

Abstract Background Lung cancer is the second most commonly diagnosed lung cancer in the world, and Non-Small Cell Lung Cancer is the most prevalent subtype. Tissue biopsy is the gold standard for detecting lung cancer, but is highly invasive as it necessitates the extraction of a sample of tissue for histologic analysis. It also carries risks of bleeding and/or infection, and is inconvenient from a patient perspective. The development of a minimally invasive test, such as one utilizing a blood or urine sample, capable of providing accurate results for lung cancer detection and/or subtyping, would significantly enhance the clinical landscape and streamline patient care. Methods In this study we utilize A549 and H1299 human lung cancer cell lines, differing in cell type, location within the lung, and genetic composition (Kras &amp; p53 status), along with two additional cancer cell lines (HeLa/cervical cancer and SCBO/bladder cancer), as controls. Cell lysate and exosome proteomics data were obtained using data independent acquisition- liquid chromatography mass spectrometry (DIA-LCMS) and analyzed using ProteoDisco 2.0, a custom-designed software application in R. Raw mass spectra data was subject to quantile normalization to mitigate external, non-biological differences between the samples. Differential protein expression was performed and Student's t-test was used to identify significantly different proteins across the sample types. A correlation coefficient matrix and Principal Component Analysis were used to assess global differences, and hierarchical clustering and heat maps allowed for visualizing of specific groups of proteins that separated all sample types. Results Over 1000 proteins were identified in each of the exosome samples, and &amp;gt;7500 proteins were detected in the lysates. Correlation coefficient matrix and PCA demonstrate that exosomal protein profiles, relative to cell lysates, are better at differentiating between the two lung cancer cell lines and controls. Surprisingly, exosomal proteomic patterns are different for the two lung cancers, implicating activation of different signaling pathways. Specifically, hierarchical clustering identified protein clusters showing enrichment for multiple biological processes: H1299 cells manifest enrichment of apical junction proteins and in epithelial-mesenchymal transition (EMT) ontology, while A549 cell lines show enrichment in proteins involved in oxidative phosphorylation. This combination of functional pathways can be used as a biomarker signature to distinguish between these two lung cancer subtypes, and from controls. Conclusions A short list of exosomal proteins, comprising apical junction, EMT, and oxidative phosphorylation constituents can detect lung cancer and further distinguish between subtypes represented by A549 and H1299 lung cancer cells. This biomarker signature has potential for detecting and subtyping lung cancer, to allow for early detection of disease, development of personalized treatment strategies, and result in improved clinical outcomes for this deadly disease.

S1497 Prevalence and Impact of Zinc Deficiency on Clinical Outcomes in Inflammatory Bowel Disease

S1497 Prevalence and Impact of Zinc Deficiency on Clinical Outcomes in Inflammatory Bowel Disease

TCT-774 Sex Differences in Prevalence, Clinical Presentation, Management Strategies and Clinical Outcomes of Valvular Heart Disease in Hospitalized Patients: Insights From a Single-Center Registry at a Tertiary Care Hospital in India

TCT-774 Sex Differences in Prevalence, Clinical Presentation, Management Strategies and Clinical Outcomes of Valvular Heart Disease in Hospitalized Patients: Insights From a Single-Center Registry at a Tertiary Care Hospital in India

Treatment with trimetazidine dihydrochloride and lung cancer survival: Implications on metabolic re-programming

BackgroundMetabolic re-wiring with preferential fatty acid oxidation has been observed in lung cancer cells. Whether the use of trimetazidine, an anti-anginal agent that inhibits fatty acid oxidation, alters clinical outcomes in ischemic heart disease (IHD) patients with lung cancers is unknown. MethodsWe carried out this territory-wide, retrospective cohort study of 279,894 IHD patients prescribed with trimetazidine or long-acting oral nitrates in Hong Kong (population coverage of 7.5 millions, January 1999 − December 2020). A total of 6561 patients with pre-existing or de novo lung cancers were identified. Clinical outcomes of all-cause mortality were longitudinally compared between lung cancer patients who received trimetazidine (n = 547) versus non-users (control, n = 6014). ResultsOver 902.9 ± 1410.6 days, lower incidence of deaths occurred in the trimetazidine group (79.0 %, n = 432/547) compared to controls (90.5 %, n = 5442/6014, P < 0.001). Kaplan-Meier analyses showed that trimetazidine use was associated with significantly higher survival from all-cause mortality in IHD patients (trimetazidine: mean survival = 1840.6 [95 %CI 1596.0–2085.3], versus control: 1056.7 [95 %CI 1011.3–1102.0] days, Log Rank = 69.4, P < 0.001). Cox regression showed that trimetazidine use was significantly associated with reduced risk of all-cause mortality in crude (HR = 0.60 [95 %CI: 0.53 to 0.68], P < 0.001) and multivariable models (HR = 0.65 [95 % CI: 0.57 to 0.74], P < 0.001). Pre-specified analyses amongst patients with pre-existing lung cancers yielded similar findings (HR = 0.49 [95 %CI: 0.35 to 0.67], P < 0.001). Survival benefits related to trimetazidine use was predominantly restricted to non-cardiovascular mortality (P < 0.001). ConclusionsTrimetazidine use is associated with higher overall survival in IHD patients with lung cancers, particularly from non-cardiovascular death. These findings need to be confirmed by randomized controlled trials.

Comparison of the activity of IL-6 and IL22 as more inflammatory cytokines related to the pathogenesis of celiac disease between active and gluten-free diet patient

This study aimed to investigate the activity of anti-inflammatory IL-6 (aIL-6) and pro-regenerative IL-22 in celiac disease patients based on their dietary habits. By comparing cytokine levels between patients on active gluten-containing diets and those on gluten-free diets, we sought to elucidate the potential role of diet in modulating inflammatory responses and clinical outcomes in celiac disease. The study made use of an enzyme-linked immunosorbent assay (ELISA) to evaluate the serum levels of interleukins IL6 and IL22. This was performed on three different groups: Group 1, which consisted of 40 recently identified active celiac patients; Group 2, which included 20 patients following a gluten-free diet; and Group 3, which contained 40 apparently healthy individuals .the individuals included in the study had been previously confirmed as celiac patients through serology, specifically by detecting both anti-IgA and IgG antibodies against tTG and gliadin using indirect immunofluorescence. The findings revealed a notable difference in IL6 levels between the patient and control groups, with a P-value of 0.041. However, when the patient groups were compared using the least significant difference (LSD) method, there were no significant differences between Group 1 (G1) and Group 2 (G2) with a P-value of 0.101, and between Group 1 and Group 3 (G3) with a P-value of 0.720. Yet, a more pronounced difference was observed between Group2 and Group3,with a P-value less than 0.015.Regarding IL22 levels, there was a significant difference between the patient and control groups, with a P-value of 0.002. Further comparisons using the LSD method revealed no significant differences between Group 1 and Group 2, with a P-value less than 0.154. However, a highly significant difference was found between Group 1 and Group 3, with a P-value less than 0.01. Also, significant differences were observed between Group 2 and Group 3, with a P-value less than 0.012. In conclusion, there is important role of the inflammatory cytokines il-6 and il-22 in the inflammation of celiac disease and potential role for these cytokines in the pathogenesis and management of the disease. Adherence to a gluten-free diet appears to have a beneficial effect on modulating the inflammatory response and improving clinical outcomes in celiac disease..

Comparison of the Activity of IL-6 and IL22 as More Inflammatory Cytokines Related to the Pathogenesis of celiac Disease Between Active and Gluten-Free Diet Patient

This study aimed to investigate the activity of anti-inflammatory IL-6 (aIL-6) and pro-regenerative IL-22 in celiac disease patients based on their dietary habits. By comparing cytokine levels between patients on active gluten-containing diets and those on gluten-free diets, we sought to elucidate the potential role of diet in modulating inflammatory responses and clinical outcomes in celiac disease. The study made use of an enzyme-linked immunosorbent assay (ELISA) to evaluate the serum levels of interleukins IL6 and IL22. This was performed on three different groups: Group 1, which consisted of 40 recently identified active celiac patients; Group 2, which included 20 patients following a gluten-free diet; and Group 3, which contained 40 apparently healthy individuals .the individuals included in the study had been previously confirmed as celiac patients through serology, specifically by detecting both anti-IgA and IgG antibodies against tTG and gliadin using indirect immunofluorescence. The findings revealed a notable difference in IL6 levels between the patient and control groups, with a P-value of 0.041. However, when the patient groups were compared using the least significant difference (LSD) method, there were no significant differences between Group 1 (G1) and Group 2 (G2) with a P-value of 0.101, and between Group 1 and Group 3 (G3) with a P-value of 0.720. Yet, a more pronounced difference was observed between Group2 and Group3,with a P-value less than 0.015.Regarding IL22 levels, there was a significant difference between the patient and control groups, with a P-value of 0.002. Further comparisons using the LSD method revealed no significant differences between Group 1 and Group 2, with a P-value less than 0.154. However, a highly significant difference was found between Group 1 and Group 3, with a P-value less than 0.01. Also, significant differences were observed between Group 2 and Group 3, with a P-value less than 0.012. In conclusion, there is important role of the inflammatory cytokines il-6 and il-22 in the inflammation of celiac disease and potential role for these cytokines in the pathogenesis and management of the disease. Adherence to a gluten-free diet appears to have a beneficial effect on modulating the inflammatory response and improving clinical outcomes in celiac disease.

Clinical Presentation and Treatment Outcomes of Adult-Onset Coats Disease

Purpose: To study the clinical profile, treatment, and outcomes of patients 35 years or older diagnosed with Coats disease. Methods: A cross-sectional observational hospital-based study was performed. Results: The study included 74 eyes diagnosed with adult-onset Coats disease. The mean age at presentation was 50 years (range, 35-75). Most patients were men (72.5%) and had a unilateral presentation (92.8%). The most common stage at presentation was 2A (extrafoveal exudation) (39.2%) followed by 2B (foveal exudation (33.7%). Optical coherence tomography was performed in 40 eyes; 32 eyes (80.0%) had intraretinal fluid (IRF), 31 eyes (77.5%) had hard exudates, and 22 eyes (55.0%) had a disorganized retinal inner layer. Fluorescein angiography was performed in 35 eyes and showed an irregular foveal avascular zone in 28 eyes (80.0%). Multiple leaking microaneurysms were seen in 32 eyes (91.4%), with extensive vascular abnormalities involving the macula (86%) and extramacular zones (91%). Treatment modalities comprised laser photoablation (43.4%), cryotherapy with or without laser application (5.7%), and intravitreal injections (49%), alone or in combination. At a mean follow-up of 28 months (range, 3-293), 23 eyes (39.6%) had anatomic resolution of subretinal fluid and/or IRF. No statistical improvement was found in the mean best-corrected visual acuity (VA) between preoperatively and postoperatively ( P &gt; .05). Conclusions: Patients with adult-onset Coats disease have a unilateral presentation with a less severe stage than patients with childhood-onset disease. Despite the good anatomic responses after treatment, the final VA remained unchanged.

Clinical Manifestations and Outcomes of Ocular Graft Versus Host Disease following Allogeneic Stem Cell Transplantation.

To evaluate clinical presentation of chronic ocular graft-versus-host disease (GVHD), laterality of presentation, and longitudinal changes in patients undergoing allogeneic stem cell transplantation. This is a retrospective longitudinal analysis of 60 eyes from 30 patients who had undergone hematopoietic stem cell transplantation. Demographic characteristics, clinical history, comorbidities, and other organ involvements were taken into account for analysis. We also undertook complete evaluation of the eyes, including cornea and anterior segment, posterior segment, Schirmer test, tear break-up time, ocular surface disease index, and intraocular pressure. The mean age of the patients was 34.3 11 years. The mean time for the diagnosis of ocular GVHD was 232.8 days (95% CI: 153.6, 311.9). The common findings at the first visit were bilateral blepharitis (n = 5, 17%), meibomitis (n = 4, 13%), and conjunctival congestion (n = 3, 10%). While bilateral cataract was present in one (3%) patient at the first visit, at 18 months, five (17%) patients had bilateral cataract and one (3%) patient had unilateral cataract. Grade 1 (n = 17), grade 2 (n = 9), and grade 3 (n = 4) superficial punctate epithelial erosions (SPEEs) were also observed at the first visit. However, SPEEs were seen in only 11 eyes at 18 months; all of these cases were grade 1 SPEEs. Long-term findings included cataract, telangiectasia, blepharospasm, conjunctival congestion, grade 1 SPEEs, corneal filaments, and tear film debris. Although the initial presentations were SPEEs, meibomitis, blepharitis, and conjunctival congestion, these inflammatory conditions were reduced over time with proper management. However, there was an increase in the proportion of patients with cataract. It is important to regularly monitor these patients in order to identify and manage the initial as well as the late ocular manifestations of chronic GVHD.

The impact of hypertension on clinical outcomes in moyamoya disease: a multicenter, propensity score-matched analysis

BackgroundMoyamoya disease (MMD) is a rare cerebrovascular disorder characterized by progressive steno-occlusive changes in the internal carotid arteries, leading to an abnormal vascular network. Hypertension is prevalent among MMD patients, raising concerns about its impact on disease outcomes. This study aims to compare the clinical characteristics and outcomes of MMD patients with and without hypertension.MethodsWe conducted a multicenter, retrospective study involving 598 MMD patients who underwent surgical revascularization across 13 academic institutions in North America. Patients were categorized into hypertensive (n=292) and non-hypertensive (n=306) cohorts. Propensity score matching (PSM) was performed to adjust for baseline differences.ResultsThe mean age was higher in the hypertension group (46 years vs. 36.8 years, p < 0.001). Hypertensive patients had higher rates of diabetes mellitus (45.2% vs. 10.7%, p < 0.001) and smoking (48.8% vs. 27.1%, p < 0.001). Symptomatic stroke rates were higher in the hypertension group (16% vs. 7.1%; OR: 2.48; 95% CI: 1.39-4.40, p = 0.002) before matching. After PSM, there were no significant differences in symptomatic stroke rates (11.1% vs. 7.7%; OR: 1.5; CI: 0.64-3.47, p = 0.34), perioperative strokes (6.2% vs. 2.1%; OR 3.13; 95% CI: 0.83-11.82, p = 0.09), or good functional outcomes at discharge (93% vs. 92.3%; OR 1.1; 95% CI: 0.45-2.69, p = 0.82).ConclusionNo significant differences in symptomatic stroke rates, perioperative strokes, or functional outcomes were observed between hypertensive and non-hypertensive Moyamoya patients. Appropriate management can lead to similar outcomes in both groups. Further prospective studies are required to validate these findings.

Clinical characteristics of pyoderma gangrenosum: Case series and literature review.

Pyoderma gangrenosum (PG) is a neutrophilic skin disease characterized by recurrent painful cutaneous ulcers, often accompanied by inflammatory bowel disease, joint pain, and other systemic damage. This disease is relatively rare in clinical practice and its diagnosis and treatment are often delayed, leading to secondary infections in the skin lesions, prolonged disease course, and increased disease burden on patients. This study retrospectively analyzed the clinical characteristics and treatment strategies of patients with PG admitted to our hospital and conducted a literature review, in order to improve the understanding of the disease among clinical doctors, enable patients to receive better diagnosis and treatment, and ultimately improve patient prognosis. Clinical data of patients diagnosed with PG and hospitalized in Beijing Chaoyang Hospital, Capital Medical University from January 2014 to December 2022 were retrospectively collected. The clinical manifestations, treatment strategies, efficacy, and disease outcomes were analyzed. A total of 14 patients, including 8 males and 6 females, aged 14 to 66 years, were included. Skin lesion types: 13 cases were ulcer-type, 1 case was pustule combined with ulcer-type, and the lower limbs were the most commonly affected areas. All the 14 patients presented with comorbidities. All patients were treated with glucocorticoids, with a daily dose equivalent to 20 to 100 mg prednisone and a median dose of 40 mg. Among them, 3 patients were treated with minocycline in combination, 1 patient was treated with mycophenolate mofetil 0.5 twice daily in combination, 1 patient was treated with cyclophosphamide 0.1 once daily in combination, and 1 patient was treated with thalidomide 0.1 every night in combination. PG is a relatively rare immune-related skin disease. Our small sample data analysis found that male PG is not uncommon in the Chinese population. Systemic glucocorticoids can quickly control the symptoms of PG in most patients with PG. In patients with poor efficacy or limited use of glucocorticoids, immunosuppressive drugs or novel targeted drugs such as biologics or small-molecule drugs should be used in combination as early as possible. Skin lesion care focuses on preventing infection, avoiding surgical debridement, and emphasizing pain management and the symptomatic treatment of comorbidities.

Cardiovascular adverse effects of antiviral therapies for COVID-19: Evidence and plausible mechanisms.

Antiviral therapeutics have made a critical contribution in mitigating the symptoms and clinical outcomes of the coronavirus disease of 2019 (COVID-19), in which a single-stranded RNA viral pathogen, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes multi-organ injuries. Several antivirals were widely prescribed to treat COVID-19, either through the emergency use authorization (EUA) by the governmental regulatory agencies (i.e., remdesivir, paxlovid, molnupiravir, and the SARS-CoV-2-targeted monoclonal antibodies - tixagevimab and cilgavimab), as well as the repurposed use of the existing antiviral or antimalarial drugs (e.g., hydroxychloroquine, chloroquine, and ivermectin). Despite their efficacy in ameliorating COVID-19 symptoms, some adverse side-effects of the antivirals were also reported during the COVID-19 pandemic. Our current review has aimed to gather and extrapolate the recently published information concerning cardiovascular adverse effects caused by each of the antivirals. We also provide further discussion on the potential cellular mechanisms underlying the cardiovascular adverse effects of the selected antiviral drugs, which should be carefully considered when evaluating risk factors in managing patients with COVID-19 or similar infectious diseases. It is foreseeable that future antiviral drug development assisted with the newest artificial intelligence platform may improve the accuracy to predict the structures of biomolecules of antivirals and therefore to mitigate their associated cardiovascular adversities.