Disease Clinical Outcome Research Articles

Sphingosine-1-Phosphate as Lung and Cardiac Vasculature Protecting Agent in SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may cause severe respiratory illness with high mortality. SARS-CoV-2 infection results in a massive inflammatory cell infiltration into the infected lungs accompanied by excessive pro-inflammatory cytokine production. The lung histology of dead patients shows that some areas are severely emphysematous, with enormously dilated blood vessels and micro-thromboses. The inappropriate inflammatory response damaging the pulmonary interstitial arteriolar walls suggests that the respiratory distress may come in a large part from lung vasculature injuries. It has been recently observed that low plasmatic sphingosine-1-phosphate (S1P) is a marker of a worse prognosis of clinical outcome in severe coronavirus disease (COVID) patients. S1P is an angiogenic molecule displaying anti-inflammatory and anti-apoptotic properties, that promote intercellular interactions between endothelial cells and pericytes resulting in the stabilization of arteries and capillaries. In this context, it can be hypothesized that the benefit of a normal S1P level is due to its protective effect on lung vasculature functionality. This paper provides evidence supporting this concept, opening the way for the design of a pharmacological approach involving the use of an S1P lyase inhibitor to increase the S1P level that in turn will rescue the lung vasculature functionality.

Evaluation of a Clinical Outcome of Resistant Gastroesophageal Reflux Disease after Treatment with Full Thickness Endoscopic Device

Abstract Introduction The full-thickness Plicator® (Ethicon Endosurgery, Sommerville, NJ, USA) was developed for endoscopic treatment of gastroesophageal reflux disease (GERD). The goal is to restructure the antireflux barrier by delivering transmural pledgeted sutures through the gastric cardia. To date, studies using this device have involved the placement of a single suture to create the plication, Aim of the Work To evaluate clinical efficacy of endosural suturing using gastroscope for patients with resistant GERD, Patients and Methods This is A Prospective study, was carried out on 25 adult patients having resistant GERD or Hiatus hernia at Gastroenterology outpatient's clinic, endoscopic center, From September 2020 to March 2020, Result According to Endoscopy, there were 20 with Esophagitis in found GERD, and 1 case with Incompetent cardia in no GERD finding, Conclusion Endoscopic full-thickness plication using the GERDx™ device improves the distal acid exposure of the esophagus, typical reflux-related symptoms and QoL in well-selected patients. This procedure might constitute an option for patients with mild GERD. Long-term outcomes are required to expand our knowledge on the effects of this procedure,

The Lone Star tick, Amblyomma americanum, salivary factors exacerbate the clinical outcome of Heartland virus disease in a small animal model

Heartland virus was first isolated in 2009 from two patients in Missouri and is transmitted by the Lone Star tick, Amblyomma americanum. To understand disease transmission and pathogenesis, it is necessary to develop an animal model which utilizes the natural route of transmission and manifests in a manner similar to documented human cases. Herein we describe our investigations on identifying A129 mice as the most appropriate small animal model for HRTV pathogenesis that mimics human clinical outcomes. We further investigated the impact of tick saliva in enhancing pathogen transmission and clinical outcomes. Our investigations revealed an increase in viral load in the groups of mice that received both virus and tick salivary gland extract (SGE). Spleens of all infected mice showed extramedullary hematopoiesis (EH), depleted white pulp, and absence of germinal centers. This observation mimics the splenomegaly observed in natural human cases. In the group that received both HRTV and tick SGE, the clinical outcome of HRTV infection was exacerbated compared to HRTV only infection. EH scores and the presence of viral antigens in spleen were higher in mice that received both HRTV and tick SGE. In conclusion, we have developed a small animal model that mimics natural human infection and also demonstrated the impact of tick salivary factors in exacerbating the HRTV infection.

An integrated organoid omics map extends modeling potential of kidney disease

Kidney organoids are a promising model to study kidney disease, but their use is constrained by limited knowledge of their functional protein expression profile. Here, we define the organoid proteome and transcriptome trajectories over culture duration and upon exposure to TNFα, a cytokine stressor. Older organoids increase deposition of extracellular matrix but decrease expression of glomerular proteins. Single cell transcriptome integration reveals that most proteome changes localize to podocytes, tubular and stromal cells. TNFα treatment of organoids results in 322 differentially expressed proteins, including cytokines and complement components. Transcript expression of these 322 proteins is significantly higher in individuals with poorer clinical outcomes in proteinuric kidney disease. Key TNFα-associated protein (C3 and VCAM1) expression is increased in both human tubular and organoid kidney cell populations, highlighting the potential for organoids to advance biomarker development. By integrating kidney organoid omic layers, incorporating a disease-relevant cytokine stressor and comparing with human data, we provide crucial evidence for the functional relevance of the kidney organoid model to human kidney disease.

The Impact of Cannabis Use on Clinical Outcomes in Inflammatory Bowel Disease: A Population-based Longitudinal Cohort Study.

Cannabis use is common in inflammatory bowel disease (IBD). Recent studies demonstrated that use of cannabis may relieve symptoms; however, it is still unclear how safe cannabis and its derivatives are for IBD patients. We performed this study to evaluate the impact of cannabis use on several key clinical outcomes in IBD. We performed a retrospective study using the TriNetX Diamond Network. Cannabis use and noncannabis use subcohorts were identified for 3 patient groups: (1) IBD, (2) Crohn's disease (CD), and (3) ulcerative colitis (UC). Baseline differences between subcohorts for each group were controlled by propensity score matching. In each group, we compared relative incidence of emergency department (ED) visits, hospitalization, corticosteroid use, opioid use, IBD-related surgery, and death between cannabis users and noncannabis users. Inflammatory bowel disease cannabis users demonstrated an increased risk for corticosteroid use (risk ratios [R],1.095; 95% CI, 1.021-1.174; P = .011), ED visits (RR, 2.143; 95% CI, 2.034-2.257; P < .001), hospitalizations (RR, 1.925; 95% CI, 1.783-2.079; P < .001) and opioid use (RR, 1.35; 95% CI, 1.14-1.6); P < .001), but not an increased risk of IBD-related surgery or death. The CD and UC groups exhibited similar outcomes, except only CD demonstrated an increased risk for corticosteroid and opioid use. Cannabis use in IBD patients is associated with several poor clinical outcomes, including increased risk of corticosteroid and opioid use, ED visits and hospitalization, though not IBD-related surgery or death. It is not clear what drives these risks or whether they are directly related to IBD-associated disease activity or other factors. Further prospective studies are warranted to more carefully investigate these relationships.

Clinical Profile and Quality of Life in Patients with Resistant to Treatment Vitiligo Lesions in Iran: Vitiligo Patients need Medico-psycho-social Assistance

Background: Vitiligo is a common chronic disease associated with physical effects, psychological impacts, and impaired quality of life (QoL). Lesions in acral areas are resistant to treatments. Since these areas are exposed and visible, they have a profound effect on patients' self-confidence. Despite the high prevalence of these conditions, information in this field, especially for Iranian patients, is scarce. Objectives: To study the clinical profile of patients with vitiligo lesions in the acral areas, assess the burden of QoL impairment, and investigate the association between patient's characteristics and their QoL outcomes Methods: A total of 84 patients with non-segmental vitiligo who had involvement in resistant treatment areas were recruited in this study. Clinical characteristics and disease outcomes, with a special emphasis on the quality of life (QoL), were investigated using the Dermatology Life Quality Index (DLQI) questionnaire. Furthermore, the extent of the disease was calculated by utilizing the Vitiligo Area Scoring Index (VASI). Descriptive and comparative analyses were conducted using SPSS software (version 29). Results: The most common comorbidity observed among the patients was various types of immune diseases. The mean total score of DLQI was 8.1, indicating a moderate effect of the disease on the patient's life since the score falls within the range of 6-10. The Kruskal-Wallis non-parametric test illustrated a significant difference in QoL among different age groups (P=0.020). The results indicated a positive, direct, and significant relationship between the extent of the disease and DLQI (r=0.269,;P=0.013). Nonetheless, the relationship between the engagement of the genital area in married patients and difficulties in sexual relations was not found to be statistically significant at α=0.05. Conclusion: The involvement of end-extremities based on existing studies is a frequent occurrence in vitiligo. These affected areas hold considerable significance in terms of the patient's quality of life (QoL) due to their prominent visibility and resistance to available treatments. Considering the high prevalence of psychological consequences, diversity in skin phototypes, and social acceptance, regional studies are necessary for more efficient and responsive medical management integrated with psychosocial assistance.

Frailty Prevalence and Association with Clinical Outcomes in Interstitial Lung Disease, Asthma, and Pleural Disease.

Frailty is a syndrome characterised by increased vulnerability to negative outcomes. Interstitial lung disease (ILD), asthma, and pleural disease are leading causes of morbidity and mortality. We aimed to investigate the prevalence and impact of frailty in adult patients with these diseases. We conducted a systematic review and meta-analysis, searching PubMed, Web of Science, The Cochrane Library, and EMBASE for studies reporting on frailty in ILD, asthma, and pleural disease. MeSH terms including interstitial lung disease, Idiopathic Pulmonary Fibrosis, Non-specific Interstitial Pneumonia, Chronic Hypersensitivity Pneumonitis, systemic sclerosis-associated ILD, connective tissue disease-associated ILD, and frailty were used as key words. The primary outcome was prevalence of frailty. Where enough contextually homogeneous studies were included, a pooled random-effects meta-analysis was performed with mortality and hospitalisation as the outcomes. The review found three studies relating to frailty in asthma. No studies relating to pleural disease and frailty were identified. The median prevalence in asthma was 9.5% (IQR, 7.8-11.3). Six relevant studies incorporating 1471 ILD patients (age 68.3 ± SD2.38; 50% male) were identified, which were either cohort or cross-sectional design rated either good or fair. The median prevalence of frailty was 48% (IQR, 25-50). There was a positive association between frail ILD patients and increased risk of long-term mortality (pooled OR, 2.33 95%CI 1.31-4.15, I2 9%). One study reported a hospitalization rate of HR = 1.97(1.32-3.06) within 6 months in frail ILD patients. Frailty is very common and associated with increased mortality in patients with ILD. There are still minimal data regarding the prevalence of frailty and its influence on the risk in this population.

Exploration of Clinical Characteristics and Drug Treatment of Inflammatory Bowel Disease Complicated with Autoimmune Diseases

Objective: To analyze the clinical characteristics and drug treatment outcomes of inflammatory bowel disease (IBD) complicated with autoimmune diseases. Methods: A total of 200 patients with IBD and autoimmune diseases were selected as the observation group from January 2022 to June 2023. In addition, 200 patients with simple IBD during the same period were selected as the control group. The general and clinical data of the two groups of patients were collected and analyzed to compare their clinical characteristics and drug treatment outcomes. Results: ① There were no significant differences in gender, age, lesion location, and clinical type between the two groups (P &gt; 0.05). However, the two groups differed significantly in terms of disease duration, severity of the condition, and extraintestinal symptoms (P &lt; 0.05). ② There was no significant difference in the use of microbial preparations between the two groups (P &gt; 0.05). The observation group had a higher usage rate of steroids compared to the control group, while the usage rate of aminosalicylate suppositories was lower in the observation group than in the control group (P &lt; 0.05). ③ There was no significant difference in treatment efficacy between the two groups (P &gt; 0.05). Conclusion: Patients with IBD complicated by autoimmune diseases have longer disease duration, more severe conditions, and more extraintestinal symptoms compared to those with simple IBD. The usage rate of steroids is higher, while the usage rate of aminosalicylate suppositories is lower in the treatment plan for the former group. Nevertheless, the overall effectiveness is comparable to that of patients with simple IBD, and the overall prognosis is relatively favorable.

Autoantibodies against the melanoma differentiation-associated protein 5 in patients with dermatomyositis target the helicase domains.

Clinical observations in patients with dermatomyositis (DM) and autoantibodies against the melanoma differentiation-associated protein 5 (MDA5) suggest that the autoantibodies contribute to the pathogenesis of MDA5(+) DM. To gain insight into the role of the anti-MDA5 autoantibodies, we aimed to identify their binding sites on the different domains of the MDA5 protein. We developed an in-house ELISA to assess the reactivity against the MDA5 domains (conformational epitopes) in plasma (n = 8) and serum (n = 24) samples from MDA5(+) patients with varying clinical manifestations and disease outcomes. The reactivities were also assessed using western blot (linearized epitopes). An ELISA-based depletion assay was developed to assess cross-reactivity among the different MDA5 domains. All eight plasma samples consistently showed reactivity towards conformational and linearized epitopes on the helicase domains of the MDA5 protein. The ELISA-based depletion assay suggests that anti-MDA5 autoantibodies specifically target each of the three helicase domains. Twenty-two of the 24 serum samples showed reactivity in the in-house ELISA and all 22 displayed reactivity towards the helicase domains of the MDA5 protein. Our data revealed that the main immunogenic targets of anti-MDA5 autoantibodies from MDA5(+) patients are the helicase domains. Considering that the helicase domains are responsible for the enzymatic activity and subsequent triggering of an inflammatory response, our findings suggest that binding of anti-MDA5 autoantibodies could alter the canonical activity of the MDA5 protein and potentially affect the downstream induction of a pro-inflammatory cascade.

Low Skeletal Muscle Mass and Clinical Outcomes in Chronic Obstructive Pulmonary Disease.

In patients with chronic obstructive pulmonary disease (COPD), decreased muscle mass is a frequently encountered comorbidity in clinical practice. However, the evaluation of muscle mass in patients with COPD in real-world practice is rare. We retrospectively reviewed the electronic medical records of all patients with COPD who underwent bioelectrical impedance analysis at least once between January 2011 and December 2021 in three hospitals. Then, we analyzed the performance rate of muscle mass measurement in the patients and the correlation between muscle mass, clinical parameters, and COPD prognosis. Among the 24,502 patients with COPD, only 270 (1.1%) underwent muscle mass measurements. The total skeletal muscle mass index was significantly correlated with albumin, alanine transaminase, and creatinine to cystatin C ratio in patients with COPD (r=0.1614, p=0.011; r=0.2112, p=0.001; and r=0.3671, p=0.001, respectively). Acute exacerbation of COPD (AE COPD) was significantly correlated with muscle mass, especially the truncal skeletal muscle mass index (TSMI) in males (r=-0.196, p=0.007). In the multivariate analysis, TSMI and cystatin C were significant risk factors for AE COPD (hazard ratio, 0.200 [95% confidence interval, CI, 0.048 to 0.838] and 4.990 [95% CI, 1.070 to 23.278], respectively). Low muscle mass negatively affects the clinical outcomes in patients with COPD. Despite its clinical significance, muscle mass measurement is performed in a small proportion of patients with COPD. Therefore, protocols and guidelines for the screening of sarcopenia in patients with COPD should be established.

A proportional incidence rate model for aggregated data to study the vaccine effectiveness against COVID-19 hospital and ICU admissions.

We develop a proportional incidence model that estimates vaccine effectiveness (VE) at the population level using conditional likelihood for aggregated data. Our model assumes that the population counts of clinical outcomes for an infectious disease arise from a superposition of Poisson processes with different vaccination statuses. The intensity function in the model is calculated as the product of per capita incidence rate and the at-risk population size, both of which are time-dependent. We formulate a log-linear regression model with respect to the relative risk, defined as the ratio between the per capita incidence rates of vaccinated and unvaccinated individuals. In the regression analysis, we treat the baseline incidence rate as a nuisance parameter, similar to the Cox proportional hazard model in survival analysis. We then apply the proposed models and methods to age-stratified weekly counts of COVID-19-related hospital and ICU admissions among adults in Ontario, Canada. The data spanned from 2021 to February 2022, encompassing the Omicron era and the rollout of booster vaccine doses. We also discuss the limitations and confounding effects while advocating for the necessity of more comprehensive and up-to-date individual-level data that document the clinical outcomes and measure potentialconfounders.

Exploring the role of tryptophanyl-tRNA synthetase and associations with inflammatory markers and clinical outcomes in COVID-19 patients: A case-control study

Tryptophanyl-tRNA synthetase (WRS) is a critical enzyme involved in protein synthesis, responsible for charging tRNA with the essential amino acid tryptophan. Recent studies have highlighted its novel role in stimulating innate immunity against bacterial and viral infections. However, the significance of WRS in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains elusive. In this study, we aimed to investigate the complex interplay between WRS, inflammatory markers, Toll-like receptor-4 (TLR-4), and clinical outcomes in coronavirus disease 19 (COVID-19) patients. A case-control investigation comprised 127 COVID-19 patients, carefully classified as severe or moderate upon admission, and 112 healthy individuals as a comparative group. Blood samples were meticulously collected before treatment initiation, and WRS, interleukin-6 (IL-6), and C-reactive protein (CRP) concentrations were quantified using a well-established commercial ELISA kit. Peripheral blood mononuclear cells (PBMCs) were isolated from the blood samples, and RNA was extracted for cDNA synthesis. Semi-quantitative real-time polymerase chain reaction (PCR) was employed to assess the relative expression of TLR-4. COVID-19 patients exhibited elevated levels of WRS, IL-6, CRP, and TLR-4 expression compared to healthy individuals, with the severe group displaying significantly higher levels than the moderate group. Notably, severe patients demonstrated substantial fluctuations in CRP, IL-6, and WRS levels over time, a pattern not observed in their moderate counterparts. Although no significant distinctions were observed in the dynamic alterations of WRS, IL-6, CRP, and TLR-4 expression between deceased and surviving patients, a trend emerged indicating higher IL-6_1 levels in deceased patients and elevated lactate dehydrogenase (LDH) levels in severe patients who succumbed to the disease. This pioneering research highlights the dynamic alterations of WRS in COVID-19 patients, providing valuable insights into the correlation between WRS, inflammatory markers, and disease severity within this population. Understanding the role of WRS in SARS-CoV-2 infection may open new avenues for therapeutic interventions targeting innate immunity to combat COVID-19.

Disc prosthesis versus fusion with cage in single level cervical degenerative spine disease – A retrospective case-control patient reported outcome study

AimTo compare the clinical outcome of single level cervical degenerative spine disease treated surgically with motion preserving anterior cervical disc arthroplasty versus anterior cervical discectomy and fusion (ACDF). MethodsPatients treated with cervical disc arthroplasty at Aalborg University Hospital and ACDF at Aarhus University Hospital were matched 1:2.Primary outcome measures were Neck Disability Index (NDI), EQ-5D-3 L and Numeric rating scale (NRS) for arm- and neck pain.Data was collected by telephone interviews regarding present and retrospective data. Results50 patients treated with cervical disc arthroplasty were matched to 100 ACDF patients covering November 2011 to December 2018.Mean improvements for NRS neck pain three-months postoperative, and NDI were significantly better in the cervical disc arthroplasty group, with intergroup differences of 1.56 (p = 0.02) and 5.01 (p = 0.01) respectively.A subgroup analysis of the half of the cohort with the longest follow-up (mean 7.6 years) showed, in favour of cervical disc arthroplasty, mean improvements of NDI: 8.80 (p = 0.00), EQ5D: − 0.19 (p = 0.04), NRS neck three months follow-up: 3.70 (p = 0.00) and long follow-up: 2.54 (p = 0.01) and NRS arm three months follow-up: 2.02 (p = 0.01).Radiologic examination indicated preserved mobility in 80% of the implanted protheses at 24-month post-surgical follow-up. ConclusionSurgical treatment of one level degenerative cervical spine disease with cervical disc arthroplasty or anterior cervical discectomy and fusion has a similar good clinical outcome after a mean follow-up of 5.6 years.However, cervical disc arthroplasty displayed long-term superiority in the half of the cohort with the longest follow-up time averaging 7.6 years.

Abstract P1163: Identifying Novel Intracellular Interactions Driving Membrane-bound Tumour Necrosis Factor-mediated Signalling In The Microvasculature

Elevated total peripheral resistance (TPR) is a hallmark of many cardiovascular diseases and furthers disease progression. We previously demonstrated that myogenic tone, regulated by membrane-bound tumour necrosis factor (mTNF) reverse signalling, is a primary modulator of TPR. Thus, inhibiting mTNF reverse signalling should reduce TPR with the potential to improve disease outcome. However, since mTNF is a ubiquitous protein with critical biological functions, its indiscriminate inhibition can cause widespread side effects. Therefore, therapeutics aiming to reduce myogenic tone and TPR must target other elements of mTNF reverse signalling. To identify these unknown participants of mTNF reverse signalling, we used proximity-dependent biotinylation coupled to mass spectrometry (BioID). Our search identified 42 high confidence hits that interact with and/or are proximal to mTNF’s cytoplasmic domain. Gene ontology (GO) analysis revealed that molecularly, these proteins are structural constituents of the cytoskeleton involved in actin and cell adhesion molecule binding. This aligns with our underlying hypothesis that mTNF functions as a mechanosensor that tethers to its receptors and initiates myogenic vasoconstriction in response to changes in transmural pressure. GO also identified proteins involved in MAPK and RhoA signalling, which are critically involved in myogenic vasoconstriction. Our most abundant hit (fold change = 12.6, p-value = 0.0023) is a cytoskeletal protein that plays a role in maintaining the structural integrity of cells. This protein also interacts with proteins involved in various signalling cascades, namely, RhoA and calcium-dependent signalling pathways. Thus, we hypothesize that this protein is essential for formation of signalling complexes with mTNF and interacts with other proteins to mediate reverse signalling . We will employ a bioluminescence-based approach to quantify the strength of all interactions detected by BioID and identify small molecule inhibitors that can disrupt these interactions. These newly discovered inhibitors could potentially be used as novel therapeutics targeting myogenic tone and hence, elevated TPR to improve disease management and clinical outcome of cardiovascular diseases.

The role of N-acetylcysteine in decreasing neutrophil-lymphocyte ratio in COVID-19 patients: A double-blind, randomized controlled trial.

N-acetylcysteine has antioxidant and anti-inflammatory activities that could potentially improve the clinical outcomes of coronavirus disease 2019 (COVID-19) patients. N-acetylcysteine potentially inhibits NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome and results in control oxidative stress and cytokine release in COVID-19 patients. The aim of this study was to assess the effect of N-acetylcysteine in reducing the neutrophil-lymphocyte ratio (NLR) in COVID-19 patients. A randomized controlled clinical trial was conducted among severe and moderate COVID-19 patients. The treatment group received oral 1200 mg daily of N-acetylcysteine (three times a day) and the standard care for COVID-19, while the control group received standard care for COVID-19 and a placebo. The NLR was determined on the first day of admission and after the seventh day of treatment. A paired Student t-test was used to compare the NLR before and after treatment while independent Student t-test was used to compare the NLR between treatment and control groups. A total of 40 severe and moderate COVID-19 were enrolled, 20 people in each group, with a mean age was 44.68±13.24 years old. The mean NLR on the first day was 9.44 in the treatment group and 8.84 in the control group. After the seventh day, the mean NLR was 4.27 and 11.54 in the treatment group and control group, respectively. The mean changes of NLR (the pre-treatment compared to post-treatment) in the treatment and control group were reduced 4.05 and increased 3.34, respectively. The NLR in treatment group significantly decreased compared to the control group (p<0.001). In conclusion, N-acetylcysteine 1200 mg daily could reduce the NLR in severe and moderate COVID-19 patients.

Impact of sex difference on clinical outcomes in acute myocardial infarction patients with single-vessel and multi-vessel disease: based on Korea Acute Myocardial Infarction Registry-National Institute of Health.

Several studies have compared clinical outcomes according to sex in patients with acute myocardial infarction (AMI). However, studies evaluating sex differences in clinical outcomes of single-vessel disease (SVD) and multi-vessel disease (MVD) in Korean patients with AMI are lacking. Therefore, this study aimed to analyze sex differences in the clinical characteristics of patients with AMI with SVD and MVD and to evaluate the impact of sex differences on the clinical outcomes in patients with AMI with SVD and MVD. A total of 11,002 AMI patients from November 2011 to June 2015 in the Korea AMI Registry, National Institute of Health, were enrolled. The current study was retrospective observational study. Patients were divided into SVD (n=5,644) and MVD (n=5,358) groups, and clinical impact of sex difference were analyzed by propensity score matching analysis and Cox proportional hazard regression model. Women were older and had poor baseline clinical characteristics than men. Propensity score-matched analysis of men and women with SVD and MVD revealed that the adjusted 3-year risk of major adverse cardiac event (MACE) (15.0% vs. 9.4%; hazard ratio, 1.86; 95% confidence interval, 1.10-3.13; P=0.020) was higher in women with SVD aged <65 years. However, the incidence and risk of MACE were similar for men and women with MVD, and those with SVD aged ≥65 years. In the present study of Korean patients with AMI, women were older and exhibited a higher prevalence of comorbidities than men. Women with SVD aged <65 years had a significantly higher risk of MACE.

Precise Assessments of Dissection Following Drug-Coated Balloon Treatment and Its Impact on Clinical Outcomes in De Novo Small Vessel Disease

Precise Assessments of Dissection Following Drug-Coated Balloon Treatment and Its Impact on Clinical Outcomes in De Novo Small Vessel Disease

Angiographic Coronary Calcification: A Simple Predictor of Long-Term Clinical Outcomes in Patients with Acute Myocardial Infarction.

Coronary calcification detected by coronary angiography is a simple risk marker for long-term clinical outcomes in stable coronary artery disease. However, the significance of angiographic coronary calcification in the culprit lesion of acute myocardial infarction (AMI) has not been fully discussed. The purpose of this retrospective study was to assess the usefulness of angiographic coronary calcification as a risk marker for long-term clinical outcomes following percutaneous coronary intervention to the culprit lesions of AMI. We included 1209 patients with AMI and divided them into the none-mild calcification group (n=923) and the moderate-severe calcification group (n=286) according to angiographic coronary calcification in the culprit lesion of AMI. The primary endpoint was the occurrence of major adverse cardiac events (MACE), which was defined as a composite of all-cause death, nonfatal MI, readmission for heart failure, and ischemia-driven target vessel revascularization. The median follow-up duration was 542 (Q1: 182, Q3: 990) days. A total of 345 MACE were observed during the study period. The occurrence of MACE was significantly greater in the moderate-severe calcification group than in the none-mild calcification group (43.4% vs. 23.9%, p＜0.001). In the multivariate Cox hazard model, moderate-severe calcification was significantly associated with MACE (hazard ratio 1.302, 95% confidence interval 1.011-1.677, p=0.041) after controlling multiple confounding factors. Angiographically moderate to severe calcification in AMI culprit lesion was associated with long-term worse clinical outcomes. Angiographic coronary calcification can be a simple risk marker in patients after AMI.

Clinical Outcomes in Patients With COVID-19 and Hematologic Disease.

Patients with hematologic diseases are at higher risk of the SARS-CoV-2 infection and more severe clinical outcomes of the coronavirus disease. CHRONOS19 is an observational prospective cohort study with the aim to determine the short and longer-term clinical outcomes, risk factors for disease severity and mortality, and rates of postinfectious immunity in patients with malignant and nonmalignant hematologic diseases and COVID-19. Overall, 666 patients were enrolled in the study, of which 626 were included in the final data analysis. The primary endpoint was 30-days all-cause mortality. Secondary endpoints included COVID-19 complications, rates of ICU admission and mechanical ventilation, outcomes of a hematologic disease in SARS-CoV-2 infected patients, overall survival, and risk factors for disease severity and mortality. Data from 15 centers were collected at 30, 90, and 180 days after COVID-19 was diagnosed and were managed using a web-based e-data capture platform. All evaluations were performed in the pre-omicron period of COVID-19 pandemic. Thirty-days all-cause mortality was 18.9%. The predominant cause of death (in 80% of cases) were COVID-19 complications. At 180 days, the majority (70%) of additional deaths were due to hematologic disease progression. At a median follow-up of 5.7 [0.03-19.04] months, 6-months overall survival was 72% [95% CI: 0.69-0.76]. One-third of patients had severe SARS-CoV-2 disease. The rate of ICU admission was 22% with 77% of these patients requiring mechanical ventilation, with poor survival rate. A univariate analysis revealed that older age (≥ 60 years), male sex, malignant hematologic disease, myelotoxic agranulocytosis, transfusion dependence, refractory disease or relapse, diabetes among comorbidities, any complications, especially ARDS alone or in combination with CRS, admission to an ICU, and mechanical ventilation were associated with higher risks of mortality. Treatment of the hematologic disease was changed, postponed, or canceled in 63% of patients. At a longer follow-up (90 and 180 days), the status of the hematologic disease changed in 7.5% of patients. Patients with hematologic disease and COVID-19 have high mortality rates, predominantly due to COVID-19 complications. At a longer-term follow-up, no significant impact of COVID-19 on the course of a hematologic disease was revealed.

More to Offer Than Direct Clinical Benefit: FDA's Vaccine Licensure Process Ignores Population Health and Social Determinants of Disease.

The current US Food and Drug Administration (FDA) licensure process underestimates the potential benefits of vaccines at both the individual and population levels by considering only direct clinical outcomes of vaccination. While all approved vaccines do protect the person who takes them from poor clinical outcomes for a specific infectious disease, many vaccines also have the potential to offer measurable, direct nonclinical benefits. For example, coronavirus disease 2019 (COVID-19) vaccinations for school-aged children may prevent school absenteeism. Also, by preventing infection or reducing its length and severity, some vaccines also protect-to some extent-the patient's immediate contacts from contracting the same disease. These nonclinical and population-level benefits are not considered as part of the FDA's current vaccine approval process, but they could be. We argue that the FDA's structured benefit-risk assessment framework, used for vaccine approvals, can and should consider both clinical and nonclinical benefits of vaccination when sufficient evidence exists to make an informed assessment. Including them could incentivize vaccine developers to measure additional vaccination effects, inform population health, and address health inequalities-including inequalities in the social determinants of health.