ABSTRACT
Introduction
While risk factors for severe COVID-19 infections have been well explored among the public, population-specific studies for the U.S. Veteran community are limited in the ...literature. By performing a comprehensive analysis of the demographics, comorbidities, and symptomatology of a population of COVID-19 positive Veterans Affairs (VA) patients, we aim to uncover predictors of death, survival, need for intubation, and need for nasal cannula oxygen support among this understudied community.
Materials and Methods
A retrospective review was conducted of 124 COVID-19 Veteran patients who were admitted from March to October 2020 to the VA Greater Los Angeles Healthcare System (IRB#2020-000272). Chi-square and Fisher’s exact tests were employed to assess differences in baseline demographic and clinical variables between Veterans who survived COVID-19 versus those who succumbed to COVID-19 illness. Multivariate logistic regression and Cox regression analyses were employed to assess predictors of outcome variables, including death, survival, need for intubation, and need for oxygen support (via nasal cannula). Covariates included a wide range of demographic, comorbidity-related, symptom-related, and summary index variables.
Results
Our study population consisted of primarily senior (average age was 73) Caucasian and African American (52.5% and 40.7%, respectively) Veterans. Bivariate analyses indicated that need for intubation was significantly associated with mortality (P = 0.002). Multivariate analyses revealed that age (P < 0.001, adjusted odds ratio (OR) = 1.16), dyspnea (P = 0.015, OR = 7.73), anorexia (P = 0.022, OR = 16.55), initial disease severity as classified by WHO (P = 0.031, OR = 4.55), and having more than one of the three most common comorbidities (hypertension, diabetes, and cardiac disease) and symptoms (cough, fever, and dyspnea) among our sample (P = 0.009; OR = 19.07) were independent predictors of death. Furthermore, age (P < 0.001, hazard ratio (HR) = 1.14), cerebrovascular disease (P = 0.022, HR = 3.76), dyspnea (P < 0.001, HR = 7.71), anorexia (P < 0.001, HR = 16.75), and initial disease severity as classified by WHO (P = 0.025, HR = 3.30) were independent predictors of poor survival. Finally, dyspnea reliably predicted need for intubation (P = 0.019; OR = 29.65).
Conclusions
Several independent predictors of death, survival, and need for intubation were identified. These risk factors may provide guidelines for risk-stratifying Veterans upon admission to VA hospitals. Additional investigations of COVID-19 prognosis should be conducted on the larger U.S. Veteran population to confirm our findings and add to the current body of literature.
Liver transplantation is the last resort for liver failure patients. However, due to the shortage of donor organs, bioengineered liver generated from decellularized whole liver scaffolds and induced ...pluripotent stem cell (iPSC)-derived hepatocytes (iPSC-Heps) is being studied as an alternative approach to treat liver disease. Nevertheless, there has been no report on both the interaction of iPSC-Heps with a liver extracellular matrix (ECM) and the analysis of recellularized iPSC-Heps into the whole liver scaffolds. In this study, we produced porcine iPSC-Heps, which strongly expressed the hepatic markers α-fetoprotein and albumin and exhibited hepatic functionalities, including glycogen storage, lipid accumulation, low-density lipoprotein uptake, and indocyanine green metabolism. Supplementation of ECM from porcine decellularized liver containing liver-derived growth factors stimulated the albumin expression of porcine iPSC-Heps during differentiation procedures. The iPSC-Heps were reseeded into decellularized liver scaffolds, and the recellularized liver was cultured using a continuous perfusion system. The recellularized liver scaffolds were transplanted into rats for a short term, and the grafts expressed hepatocyte markers and did not rupture. These results provide a foundation for development of bioengineered liver using stem cell and decellularized scaffolds.
Pulmonary fibrosis (PF) is a fatal chronic disease characterized by accumulation of extracellular matrix and thickening of the alveolar wall, ultimately leading to respiratory failure. PF is thought ...to be initiated by the dysfunction and aberrant activation of a variety of cell types in the lung. In particular, several studies have demonstrated that macrophages play a pivotal role in the development and progression of PF through secretion of inflammatory cytokines, growth factors, and chemokines, suggesting that they could be an alternative therapeutic source as well as therapeutic target for PF. In this review, we describe the characteristics, functions, and origins of subsets of macrophages involved in PF and summarize current data on the generation and therapeutic application of macrophages derived from pluripotent stem cells for the treatment of fibrotic diseases. Additionally, we discuss the use of macrophage-derived exosomes to repair fibrotic lung tissue.
Artificial bone grafting is widely used in current orthopedic surgery for bone defect problems. Unfortunately, surgeons remain unsatisfied with the current commercially available products. One of the ...major complaints is that these products cannot provide sufficient mechanical strength to support the human skeletal structure. In this study, we aimed to develop a bone scaffold with better mechanical property and good cell affinity by 3D printing (3DP) techniques. A self-developed 3D printer with laser-aided gelling (LAG) process was used to fabricate bioceramic scaffolds with inter-porous structures. To improve the mechanical property of the bioceramic parts after heating, CaCO3 was added to the silica ceramic slurry. CaCO3 was blended into a homogenous SiO2-sol dispersion at weight ratios varying from 0/100 to 5/95 to 9/91 (w/w). Bi-component CaCO3/SiO2-sol was prepared as a biocomposite for the 3DP scaffold. The well-mixed biocomposite was used to fabricate the bioceramic green part using the LAG method. The varied scaffolds were sintered at different temperatures ranging from 900 to 1500°C, and the mechanical property was subsequently analyzed. The scaffolds showed good property with the composite ratio of 5:95 CaCO3:SiO2 at a sintering temperature of 1300°C. The compressive strength was 47 MPa, and the porosity was 34%. The topography of the sintered 3DP bioceramic scaffold was examined by SEM, EDS and XRD. The silica bioceramic presented no cytotoxicity and good MG-63 osteoblast-like cell affinity, demonstrating good biocompatibility. Therefore, the new silica biocomposite is viable for fabricating 3DP bone bioceramics with improved mechanical property and good cell affinity.
Adipokines contribute directly to the atherosclerotic process, connecting metabolic disorders such as obesity and diabetes to cardiovascular disease. Omentin-1 is a recently discovered novel ...adipokine, so data about the relationship of this adipokine to vascular health in type 2 diabetes is limited.
We enrolled 60 people with type 2 diabetes, with or without carotid plaque, and 30 participants with normal glucose tolerance. We measured serum omentin-1, high-sensitivity C-reactive protein (hsCRP) levels, and the homeostasis model assessment of insulin resistance (HOMA-IR), as well as other cardiovascular risk factors. Vascular health was assessed by brachial ankle pulse wave velocity (baPWV) and carotid intima-media thickness (IMT).
Serum omentin-1 levels were significantly decreased in type 2 diabetes patients compared to normal glucose controls and was further reduced in type 2 diabetes patients with carotid plaque compared to those without carotid plaque. Multiple stepwise regression analysis showed that age, systolic blood pressure, history of use of statins, angiotensin receptor blockers or angiotensin-converting enzyme inhibitors, and serum omentin-1 level were independent factors determining baPWV in people with type 2 diabetes (r2 = 0.637). Furthermore, in multivariate logistic regression analysis, circulating omentin-1 level was an independent decisive factor for the presence of carotid plaque in type 2 diabetes patients, even after adjusting for age, gender, body mass index, systolic blood pressure, fasting blood glucose, low density lipoprotein cholesterol, and history of smoking and medication (odds ratio, 0.621; 95% confidence interval, 0.420-0.919; P = 0.017).
Circulating omentin-1 level was independently correlated with arterial stiffness and carotid plaque in type 2 diabetes, even after adjusting for other cardiovascular risk factors and detailed medication history.
Abstract
Ear- and hearing-related conditions pose a significant global health burden, yet public health policy surrounding ear and hearing care (EHC) in low- and middle-income countries is poorly ...understood. The present study aims to characterize the inclusion of EHC in national health policy by analysing national health policies, strategies and plans in English, French, Spanish, Portuguese and Arabic. Three EHC keywords were searched, including ear*, hear* and deaf*. The terms ‘human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS)’, ‘tuberculosis’ and ‘malaria’ were included as comparison keywords as these conditions have historically garnered political priority in global health. Of the 194 World Health Organization Member States, there were 100 national policies that met the inclusion criteria of document availability, searchable format, language and absence of an associated national EHC strategy. These documents mentioned EHC keywords significantly less than comparison terms, with mention of hearing in 15 documents, ears in 11 documents and deafness in 3 documents. There was a mention of HIV/AIDS in 92 documents, tuberculosis in 88 documents and malaria in 70 documents. Documents in low- and middle-income countries included significantly fewer mentions of EHC terms than those of high-income countries. We conclude that ear and hearing conditions pose a significant burden of disease but are severely underrepresented in national health policy, especially in low- and middle-income countries.
Context The long-term effects of metformin in women with polycystic ovarian syndrome (PCOS) are inadequately studied. Objective The effects of metformin on women with PCOS during 24 months with ...respect to menses, hormones, and metabolic profiles are assessed. Design Prospective cohort. Setting A reproductive endocrinology clinic in a university-affiliated medical center. Patients One hundred nineteen women with PCOS, defined by the Rotterdam criteria, were enrolled. Intervention Metformin was given daily for 24 months. Main Outcome Measures The primary outcome was the proportion of patients with regular menstruation during treatment. Changes in anthropometric, hormonal, and metabolic parameters were also assessed. Analyses were performed using segmented regression analysis with a generalized estimating equation methodology. Outcomes are expressed as magnitude of change from the baseline. Results Both overweight (OW) and normal-weight (NW) women with PCOS had increased menstrual frequency and decreased body mass index (BMI), testosterone, and luteinizing hormone levels in the first 6 months. Further stratification showed that NW women exhibiting elevated testosterone at baseline had the largest magnitude of improvement at 6 months odds ratio (OR), 7.21; 95% confidence interval (CI), 2.35 to 22.17, whereas OW patients with normal testosterone were most likely to achieve normal menses at 12 months (OR, 0.63; 95% CI, 0.47 to 0.77). Conclusions Metformin was associated with improvements in the menstrual cycle and most hormonal profiles in OW and NW women with PCOS during 24 months of treatment. Most parameters reached maximal response and steady-state after 6 months. Phenotypic differences in baseline BMI and testosterone level can be used as patient selection criteria or treatment prognostics.
We evaluated whether Alberta Stroke Program Early Computed Tomography Score (ASPECTS) with some modifications could be used to predict neurological outcomes in patients after extracorporeal ...cardiopulmonary resuscitation (ECPR).
This was a retrospective, multicenter, observational study of adult unconscious patients who were evaluated by brain computed tomography (CT) within 48 hours after ECPR between May 2010 and December 2016. ASPECTS, bilateral ASPECTS (ASPECTS-b), and modified ASPECTS (mASPECTS) were assessed by ROC curves to predict neurological outcomes. The primary outcome was neurological status upon hospital discharge assessed with the Cerebral Performance Categories (CPC) scale.
Among 58 unconscious patients, survival to discharge was identified in 25 (43.1%) patients. Of these 25 survivors, 19 (32.8%) had good neurological outcomes (CPC score of 1 or 2). Interrater reliability of CT scores was excellent. Intraclass correlation coefficients of ASPECTS, ASPECTS-b, and mASPECTS were 0.918 (95% CI, 0.865-0.950), 0.918 (95% CI, 0.866-0.951), and 0.915 (95% CI, 0.860-0.949), respectively. The predictive performance of mASPECTS for poor neurological outcome was better than that of ASPECTS or ASPECTS-b (C-statistic for mASPECTS vs. ASPECTS, 0.922 vs. 0.812, p = 0.004; mASPECTS vs. ASPECTS-b, 0.922 vs. 0.818, p = 0.003). A cutoff of 25 for poor neurological outcome had a sensitivity of 84.6% (95% CI, 69.5-94.1%) and a specificity of 89.5% (95% CI, 66.9-98.7%) in mASPECTS.
mASPECTS might be useful for predicting neurological outcomes in patients after ECPR.
Upadacitinib is an oral Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, and tyrosine kinase 2. We aimed to assess the efficacy and safety of upadacitinib ...compared with placebo for the treatment of moderate-to-severe atopic dermatitis.
Measure Up 1 and Measure Up 2 were replicate multicentre, randomised, double-blind, placebo-controlled, phase 3 trials; Measure Up 1 was done at 151 clinical centres in 24 countries across Europe, North and South America, Oceania, and the Asia-Pacific region; and Measure Up 2 was done at 154 clinical centres in 23 countries across Europe, North America, Oceania, and the Asia-Pacific region. Eligible patients were adolescents (aged 12–17 years) and adults (aged 18–75 years) with moderate-to-severe atopic dermatitis (≥10% of body surface area affected by atopic dermatitis, Eczema Area and Severity Index EASI score of ≥16, validated Investigator's Global Assessment for Atopic Dermatitis vIGA-AD score of ≥3, and Worst Pruritus Numerical Rating Scale score of ≥4). Patients were randomly assigned (1:1:1) using an interactive response technology system to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily for 16 weeks, stratified by baseline disease severity, geographical region, and age. Coprimary endpoints were the proportion of patients who had achieved at least a 75% improvement in EASI score from baseline (EASI-75) and the proportion of patients who had achieved a vIGA-AD response (defined as a vIGA-AD score of 0 clear or 1 almost clear with ≥2 grades of reduction from baseline) at week 16. Efficacy was analysed in the intention-to-treat population and safety was analysed in all randomly assigned patients who received at least one dose of study drug. These trials are registered with ClinicalTrials.gov, NCT03569293 (Measure Up 1) and NCT03607422 (Measure Up 2), and are both active but not recruiting.
Between Aug 13, 2018, and Dec 23, 2019, 847 patients were randomly assigned to upadacitinib 15 mg (n=281), upadacitinib 30 mg (n=285), or placebo (n=281) in the Measure Up 1 study. Between July 27, 2018, and Jan 17, 2020, 836 patients were randomly assigned to upadacitinib 15 mg (n=276), upadacitinib 30 mg (n=282), or placebo (n=278) in the Measure Up 2 study. At week 16, the coprimary endpoints were met in both studies (all p<0·0001). The proportion of patients who had achieved EASI-75 at week 16 was significantly higher in the upadacitinib 15 mg (196 70% of 281 patients) and upadacitinib 30 mg (227 80% of 285 patients) groups than the placebo group (46 16% of 281 patients) in Measure Up 1 (adjusted difference in EASI-75 response rate vs placebo, 53·3% 95% CI 46·4–60·2 for the upadacitinib 15 mg group; 63·4% 57·1–69·8 for the upadacitinib 30 mg group) and Measure Up 2 (166 60% of 276 patients in the upadacitinib 15 mg group and 206 73% of 282 patients in the upadacitinib 30 mg group vs 37 13% of 278 patients in the placebo group; adjusted difference in EASI-75 response rate vs placebo, 46·9% 39·9–53·9 for the upadacitinib 15 mg group; 59·6% 53·1–66·2 for the upadacitinib 30 mg group). The proportion of patients who achieved a vIGA-AD response at week 16 was significantly higher in the upadacitinib 15 mg (135 48% patients) and upadacitinib 30 mg (177 62% patients) groups than the placebo group (24 8% patients) in Measure Up 1 (adjusted difference in vIGA-AD response rate vs placebo, 39·8% 33·2–46·4 for the upadacitinib 15 mg group; 53·6% 47·2–60·0 for the upadacitinib 30 mg group) and Measure Up 2 (107 39% patients in the upadacitinib 15 mg group and 147 52% patients in the upadacitinib 30 mg group vs 13 5% patients in the placebo group; adjusted difference in vIGA-AD response rate vs placebo, 34·0% 27·8–40·2 for the upadacitinib 15 mg group; 47·4% 41·0–53·7 for the upadacitinib 30 mg group). Both upadacitinib doses were well tolerated. The incidence of serious adverse events and adverse events leading to study drug discontinuation were similar among groups. The most frequently reported treatment-emergent adverse events were acne (19 7% of 281 patients in the upadacitinib 15 mg group, 49 17% of 285 patients in the upadacitinib 30 mg group, and six 2% of 281 patients in the placebo group in Measure Up 1; 35 13% of 276 patients in the upadacitinib 15 mg group, 41 15% of 282 patients in the upadacitinib 30 mg group, and six 2% of 278 patients in the placebo group in Measure Up 2), upper respiratory tract infection (25 9% patients, 38 13% patients, and 20 7% patients; 19 7% patients, 17 16% patients, and 12 4% patients), nasopharyngitis (22 8% patients, 33 12% patients, and 16 6% patients; 16 6% patients, 18 6% patients, and 13 5% patients), headache (14 5% patients, 19 7% patients, and 12 4% patients; 18 7% patients, 20 7% patients, and 11 4% patients), elevation in creatine phosphokinase levels (16 6% patients, 16 6% patients, and seven 3% patients; nine 3% patients, 12 4% patients, and five 2% patients), and atopic dermatitis (nine 3% patients, four 1% patients, and 26 9% patients; eight 3% patients, four 1% patients, and 26 9% patients).
Monotherapy with upadacitinib might be an effective treatment option and had a positive benefit–risk profile in adolescents and adults with moderate-to-severe atopic dermatitis.
AbbVie.
In ischemic stroke patients undergoing endovascular treatment (EVT), we aimed to test the hypothesis that cerebral microbleeds (CMBs) are associated with clinical outcomes, while estimating the ...mediating effects of hemorrhagic transformation (HT), small-vessel disease burden (white matter hyperintensities, WMH), and procedural success. From a multicenter EVT registry, patients who underwent pretreatment MR imaging were analyzed. They were trichotomized according to presence of CMBs (none vs. 1-4 vs. ≥ 5). The association between CMB burden and 3-month mRS was evaluated using multivariable ordinal logistic regression, and mediation analyses were conducted to estimate percent mediation. Of 577 patients, CMBs were present in 91 (15.8%); 67 (11.6%) had 1-4 CMBs, and 24 (4.2%) had ≥ 5. Increases in CMBs were associated with hemorrhagic complications (β = 0.27 0.06-0.047, p = 0.010) in multivariable analysis. The CMB effect on outcome was partially mediated by post-procedural HT degree (percent mediation, 14% 0-42), WMH (23% 7-57) and lower rates of successful reperfusion (6% 0-25). In conclusion, the influence of CMBs on clinical outcomes is mediated by small-vessel disease burden, post-procedural HT, and lower reperfusion rates, listed in order of percent mediation size.
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