bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low Levels of Vitamin D Are Associated With Markers of Immuno-Inflammatory Response and Clinical Outcome in Covid-19
Authors: Filippo Luigi di , Allora Agnese , Doga Mauro , Querini Patrizia Rovere , Locatelli Massimo , Frara Stefano , Giustina Andrea 
Published: May 2021

Abstract
High prevalence of vitamin D (VD) deficiency in COVID-19 patients was reported by several studies. Since VD is a key regulating factor of both innate and adaptive immunity, it was hypothesized that VD deficiency may predispose to SARS-CoV-2 infection and lower levels of VD could be related to increased COVID-19 severity and worse outcome risks. However, to date, only few studies partially investigated the relationship between VD and inflammatory and immune response and clinical features of COVID-19 patients. The aim of this study is to evaluate the influence of vitamin D levels on COVID-19 inflammatory activity, clinical pattern and disease severity. Patients admitted to San Raffaele University Hospital for COVID-19 from February 2020 were enrolled in this study. We excluded patients with comorbidities and therapies influencing VD metabolism. 25OH-Vitamin D levels were evaluated at admission in hospital and VD insufficiency and deficiency were defined as VD level below 30 ng/mL and 20 ng/mL, respectively. A total of 88 patients were included in the study. Median (IQR) VD levels were 16.3 (11.2–23.9) ng/mL. VD insufficiency and deficiency were found in 88.6% and in 68.2% of patients, respectively. Linear regression analyses showed a positive correlation between VD levels and PaO2/FiO2 ratio (p=0.019; r=0.254), and negative correlations between VD levels and Neutrophil/Lymphocyte (N/L) ratio (p=0.04; r=-0.19), C-reactive protein (CRP) levels (p=0.047; r=-0.18) and Interleukin 6 (IL-6) levels (p=0.04; r=-0.22). Lower VD levels were found in patients affected by severe disease (needs for high-flow oxygen therapy and/or noninvasive mechanical ventilation, admitted to ICU and/or dead) than non-severe patients (13.4 ng/mL [10.37–19.15] vs 18.45 ng/mL [15.15–24.95]; p=0.007). Moreover, patients with VD deficiency had higher levels of CRP, LDH, IL-6, IFN-gamma (p=0.04, p=0.01, p=0.002, p=0.04; respectively), lower PaO2/FiO2 and higher N/L ratios (p=0.008, p=0.004; respectively), and higher rate of severe disease (65% vs 39%, p=0.02), as compared to VD non-deficient ones. In conclusion, low VD levels are widely found in hospitalized COVID-19 and may lead to increased disease severity through an excessive immune-inflammatory response. Our data suggest that reaching adequate vitamin D levels in risky population may contribute to prevention of COVID-19 occurrence and severity.
Secondary Hyperparathyroidism, Bone Density and Bone Turnover After Bariatric Surgery: Differences Between Roux-en-Y Gastric Bypass and Sleeve Gastrectomy
Authors: Holanda Narriane Chaves Pereira , Borges Heloisa Calegari , Limeira Caio Chaves de Holanda , Bezerra Louise Raya , Lima Silvane Katarine Medeiros , Carvalho Carolina Cabral , Menezes Kaue Tavares , Carvalho Nara Nóbrega Crispim , Montenegro Ana Carla , Bandeira Francisco Farias 
Published: May 2021

Abstract
Introduction: Although malabsorption of nutrients and changes in intestinal adipokines and gut hormones induced by Roux-en-Y gastric bypass (RYGB) are considerably different than sleeve gastrectomy (SG), little is known about the consequences on bone health resulted by these two procedures. Objective: to compare the prevalence of secondary hyperparathyroidism (SHPT), bone mineral density (BMD), bone turnover markers and serum leptin in obese patients undergoing RYGB and SG, according to the time of surgery and percent weight loss. Methods: we studied 117 patients (91% female, 51% RYGB, mean age 41.8 ± 6.7 years, mean time of surgery 4.3 ± 3.4 years) who were divided into two groups according to the surgical procedure adopted (SG vs. RYGB). They were evaluated at different times after surgery (1–2 years, &gt; 2 and &lt;5 years and ≥5 years) and according to the percentage of weight loss (10–20%, &gt;20% and &lt;40%, ≥40%). Anthropometric measurements, body composition and BMD, bone parameters (PTH, corrected serum calcium, 25OHD, alkaline phosphatase -AP, C-telopeptide - CTX), and biochemical tests were compared. Results: The prevalence of SHPT (PTH ≥ 65pg/ml) was 26%, higher in the RYGB vs. SG (35% vs. 17%, respectively, p = 0.039), despite no significant differences in serum 25OHD (28.5 ± 7.3 vs. 27.6 ± 7.7 ng/ml, p=0.519) and corrected serum calcium (9.8 ± 0.6 vs. 9.8 ± 0.5 mg/dl, p = 0.466) between the groups. Mean serum PTH, CTX and AP was higher in the RYGB vs. SG (61.3 ± 29.5 vs 49.5 ± 32.3 pg/mL, p = 0.001; 0.596 ± 0.24 vs. 0.463 ± 0.23 ng/mL; 123.9 ± 60.8 vs. 100.7 ± 62.0 U/L, respectively). There were 13.5% decreases in femoral neck BMD in all patients, over the study period. After 5 years of surgery, the RYGB group showed greater bone loss in total body BMD (1.016 vs. 1.151g/cm2, -8.1%, p = 0.003) and total femur BMD (1.164 vs. 1.267g/cm2, - 11.7%, p = 0.007). Mean serum leptin was lower in the RYGB group, when compared to SG (7.6 ± 5.8ng/mL vs. 14.0 ± 9.9, p = 0.001), with no correlation with BMD in any site. There were no significant differences between the RYGB and SG regarding the other metabolic parameters. Conclusion: We found a more deleterious effect of RYGB on bone health up to 5 years postoperatively in comparison with SG.
Vitamin D Status as a Potential Modifiable Risk Factor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Authors: Saponaro Federica 
Published: May 2021

Abstract
In March 2020, the infection COVID-19 spread as a pandemic emergence. Among multiple biological and environmental factors, hypovitaminosis D is a credible candidate. The aim of this study is to shed light on the pathogenic role of vitamin D deficiency in the susceptibility to SARS-CoV-2 and in the aggressive immune and inflammatory response by the host. We retrospectively analyzed the biochemical panel of immune system markers and the tandem mass spectrometry coupled to liquid chromatography (LC-MS-MS) measured vitamin D, in the serum samples of patients with SARS-CoV-2 studied in all aspects of clinical relevant parameters. RESULTS between 18th March and 20th April 2020 we enrolled 29 consecutive patients with COVID-19. They were 17 (58.6%) males and 12 (41.4) females, and the median age was 79 (69–88) years. Mean 25OHD was 17.3±2.1 ng/ml, with a median of 15.7 1 ng/ml (i.r. 6.7–25). Twenty-five patients (86.2%) had 25OHD levels &lt;30 ng/ml, 18 patients (62.0%) had 25OHD levels &lt;20 ng/ml and 10 patients (34.5%) had severe vitamin D deficiency (&lt;10 ng/ml). In the group of patients with severe disease (ARDS, cardiovascular complications, CID) 69.2% (n=9/13) of patients presented hypovitaminosis D (&lt;20 ng/ml). All patients who dead for COVID-19 during hospitalization (n=6) had 25OHD≤30 ng/ml and 5/6 had 25OHD≤20 ng/ml. IL-6 and CRP were measured in all patients and were considered surrogate markers of cytokines storm. The majority of patients had levels of IL-6 (n=22, 75.8%) and CRP (n=25, 86.2%) above the upper limit of the reference range of our laboratory (IL6 6.59 and CRP 1 mg/dl) and the median was IL 6=16.1 (i.r. 7.3–36.3) and CRP=6.67 (2.64–11.52). Patients with 25OHD &lt;20 ng/ml had higher levels of IL-6 (p=0.004; 19.9 vs 10.4) and CRP (p=0.009, 9.85 vs 1.40) and did not differ for the other clinical and biochemical variables. If we considered as 25OHD cut-off the mean value in our population (17.3 ng/ml), patients with lower levels of 25OHD had higher age (p=0.033) and higher levels of IL6 (p=0.016), CRP (p=0.04), troponin (p=0.04) and D-dimer (p=0.017), compared to the others. An inverse correlation was found between 25OHD levels and IL-6, CRP, and troponin. In a univariate regression analysis hypovitaminosis D (&lt;20 ng/ml) was a predictive factor for IL6 (expressed as LnIL6) levels (β=0.57, P=0.003) and for PCR levels (β=0.42, P=0.034). We also performed a multivariate regression analysis with hypovitaminosis D (&lt;20 ng/ml), sex, BMI, age (&lt;70 years) and ARDS as independent variables. Notably, hypovitaminosis D (β=0.49, P&lt;0.02), BMI (β=0.4, P=0.04) and ARDS (β=0.44, P=0.02) were confirmed to be significant variables for IL6 (expressed as LnIL6) level prediction. In the same multivariate model hypovitaminosis D (β=0.49, P=0.034) was confirmed as independent predictor of CRP levels. In conclusion, hypovitaminosis D is related to the negative prognostic inflammatory status in patients with SARS-Cov2.
Effect of Chronic Kidney Disease on Outcome of Adult Patient Admitted With Hyperthyroidism: Analysis of the National Inpatient Sample 2016–2017
Authors: Shaka Hafeez , Asemota Iriagbonse , Akuna Emmanuel , Edigin Ehizogie , Velazquez Genaro , Ojemolon Pius , Asotibe Jennifer Chiagoziem 
Published: May 2021

Abstract
Introduction: Kidney and thyroid function and dysfunction are interrelated through several mechanisms. Thyroid hormones can also have significant impact on kidney disease so it is important to consider the physiological association of thyroid dysfunction in relation to chronic kidney disease (CKD). Research shows that hyperthyroidism is usually not associated with CKD but is known to accelerate it. We sought to determine the effect of chronic kidney disease on patient admitted with hyperthyroidism.
Methods: We queried the National Inpatient Sample (NIS) databases from 2016 to 2017 for adults aged 18 and above with hyperthyroidism as a principle diagnosis with and without hypertriglyceridemia using ICD-10 codes. Multivariate logistic and linear regression analysis was used accordingly to adjust for confounders
Results: There were over 71 million discharges in the combined 2016 and 2017 NIS database. Out of 17,705 hyperthyroidism hospitalizations, 4% had chronic kidney disease. Chronic kidney disease with hyperthyroidism had a similar odd of inpatient mortality (AOR 0.79, CI 0.34–4.52, P= 0.787) and cardiogenic shock (AOR 2.66, CI 0.35–20.50, P=0.347). There was a statistically significant increase in odds of acute kidney injury (AOR 2.77, CI 1.60- 4.80, P &lt;0.001) in those hospitalized with hyperthyroidism and chronic kidney disease compared to those with hyperthyroidism alone
Conclusion: Chronic kidney disease is associated with similar odds of hospital mortality and cardiogenic shock among patients hospitalized for hyperthyroidism with increased odds of acute kidney injury compared to those without hyperthyroidism. It is very important to consider all clinical features and thyroid manifestations in those patients with CKD.
Identification of Diagnostic Plasma Biomarkers of Coronary Microvascular Disease in Postmenopausal Women Using Machine Learning Methods
Authors: Eve Alicia Arredondo , Tunc Elif , Liu Yu-Jeh , Agrawal Saumya , Yilmaz Huriye Huriye Erbak , Emren Sadik Volkan , Akcay Filiz Akyildiz , Mainzer Luidmila , Zurauskiene Justina , Madak-Erdogan Zeynep 
Published: May 2021

Abstract
Introduction: Coronary microvascular disease (CMD) affects small arteries that feed the heart and is more prevalent in postmenopausal women. Since CMD and Coronary artery disease (CAD) have distinct pathologies, but are treated the same way, the majority of the patients with CMD do not receive a proper diagnosis and treatment, which in turn results in higher rates of adverse future events such as heart failure, sudden cardiac death, and acute coronary syndrome (ACS). Previously, we performed full metabolite profiling of plasma samples using GC-MS analysis and tested their classification performance using machine learning approaches. This initial proof-of-concept study showed that plasma metabolite profiles can be used to develop diagnostic signatures for CMD. In the current study, we hypothesize that plasma metabolite and protein composition is different for postmenopausal women with no heart disease, with CAD, or with CMD. Methods: We obtained plasma samples from 70 postmenopausal women who are healthy, women who have CMD, and women who have CAD at the time of blood collection. In addition to GC-MS metabolite profiles, we performed LC-MS metabolomic profiling, and proteomic profiling of a panel of 92 proteins that were implicated in cardiometabolic disease. We identified a combination of metabolites and proteins, and further tested their classification performance using machine learning approaches to identify potential circulating biomarkers for CMD. Results: We identified a comprehensive list of metabolites and proteins that were involved in endothelial cell function, nitric oxide metabolism and inflammation, which significantly different in plasma from women with CMD. We further validated difference in the level of several protein biomarkers, such as RAGE, PTX3, AGRP, CNTN1, and MMP-3, which are statistically significantly higher in postmenopausal women with CMD when compared with healthy women or women with CAD. Conclusion: Our research identified a group of potential molecules that can be used in the design of easy and low-cost blood biomarkers for the clinical diagnosis of CMD.
Improvement in Quality of Life and Psychological Symptoms After Treatment for Primary Aldosteronism
Authors: Puar Troy , Kwan Yu Heng , Tan Pei Ting , Teo David , Ng Keng Sin , Zhang Meifen , Deinum Jaap , Velema Marieke Stientje , Tan Yen Kheng 
Published: May 2021

Abstract
Background: Primary aldosteronism (PA) is the most common treatable cause of secondary hypertension. In addition to increased cardiovascular risk, patients also suffer from impaired quality of life (QoL) and psychological symptoms. We assessed for changes in QoL and depressive symptoms in a cohort of Asian patients with PA, after surgical and medical therapy. Methods: We administered questionnaires to 34 patients with PA, mean age, 51.3 years, 29.4% females, in a prospective observational study from 2017 to 2020. QoL was assessed using RAND-36 and EQ-5D-3L, and depressive symptoms was assessed using Beck Depression Inventory (BDI-II) at baseline, 6 months, and 1 year post-treatment. Results: Significant improvement was observed 1 year after treatment in both physical and mental summative scores of RAND-36 from baseline, +3.65 (p = 0.023) and +3.41 (p = 0.033) respectively, as well as four subscale domains (physical functioning, bodily pain, role emotional and mental health). Significant improvement was also seen in EQ-5D dimension of anxiety/depression at 1 year post-treatment. Patients treated with surgery (N=21) had significant improvement in EQ-5D index score post-treatment, and better EQ-5D outcomes compared to medical group (N=13) at 1 year post-treatment. 37.9%, 41.6% and 60.7% of patients had symptoms in the cognitive, affective and somatic domains of the BDI-II respectively. There was significant improvement in the affective domain of BDI after 1 year of treatment. Conclusion: Appropriate treatment with surgical and medical therapy improves QoL and psychological symptoms in patients with PA, highlighting the importance of early diagnosis and treatment of this common condition.
Prevalence of Dyslipidemia and Evaluation of the Influence of Body Composition, Physical Activity and Food Standard in the Serum Lipids of Low Risk Pregnant Women: A Cross-Study
Authors: Bomfim Boaventura Olivia Carla , Feitosa Alina Coutinho Rodrigues 
Published: May 2021

Abstract
The impact of maternal dyslipidemia (DLP) on fetal injury development occurs even in situations of transient DLP during pregnancy. Some authors define gestational DLP when the CT, LDL and TG concentrations are above the 95th percentile (P95%) and HDL, below the 5th percentile (P5%) for gestational age, but there is no consensus. OBJECTIVE: To compare the prevalence of DLP in pregnant women using percentiles criteria with the V Brazilian Guidelines on Dyslipidemia and to evaluate the association of lipid profile with body composition, physical activity(PA) practice and dietary pattern. Methods: A unicentric cross-sectional study that evaluated low-risk pregnant women between 18 and 45 years old in two maternity hospitals in the city of Salvador-BA. Using a standardized questionnaire, sociodemographic data and clinical and health characteristics, nutritional status and PA practice were evaluated, as well as lipid profile measurement in any trimester of pregnancy, classifying pregnant women according to presence of DLP by two criteria. The food intake was quantified through the 24-hour food survey, obtaining the nutritional composition of the food with the aid of the NutWin® program and the intensity of the PA was assessed by means of the PA questionnaire for pregnant women (PAQP). Bioimpedance was used for body composition analysis. Statistical analysis was performed and a p value &lt;0.05 was considered. Results: 165 pregnant women aged 28.6 ± 6.3 years were studied, with 57.6% in the 3rd trimester. Although only 13.9% of pregnant women were obese, with an average PGC of 36.2 ± 5.6%, there was distortion of self body image. Dairy and carbohydrate intake was out of the international recommendation range. The prevalence of any lipid alterations, according to the National Guideline criteria, was 84.7%:TC ≥ 200 mg / dL was found in 62.9%; LDL ≥ 160 mg / dL in 15.3%, HDL ≤ 50 mg / dL in 12.6% and TG ≥ 150 mg / dL in 59.6%. The prevalence of dyslipidemia by the percentile criterion was found in only 4%, with an increase higher than P95% for TC was found in 0.7%; for LDL, in 0.7%; for TG in 2.6% and below P5% for HDL in 2%. About 99.4% of the pregnant women had energy expenditure above 6.0 metabolic equivalents (METs). There was a positive correlation (p = 0.035, r=0.276) between body fat percentage and LDL values, between VLDL concentration and amount of carbohydrates ingested (p = 0.047, r 0.168) and an inversely proportional association between HDL analyzes and cervical circumference (p = 0.010, r= -0.227). There was no association of lipid profile with perception of body self-image, physical activity or eating pattern. Conclusion: The prevalence of dyslipidemia assessed by the criterion of the V Brazilian Dyslipidemia Guideline for adults was significantly higher than the prevalence identified by the criterion of specific pregnancy percentiles.
Stable Serum Potassium After Intracerebral Hemorrhage Is Predictive of Primary Aldosteronism
Authors: Arai Makoto , Kiko Katsunari , Oya Shigeru 
Published: May 2021

Abstract
Background: Primary aldosteronism (PA) is a well-known risk factor for cardiovascular complications including intracerebral hemorrhage (ICH). Still, there seem to be many PA patients who have been missing the opportunities for the diagnosis of PA even after stroke. PA screening tests in all stroke patients are, however, inefficient. Here we focused on ICH, where hypertension has a great contribution, and searched for the indications of performing PA screening tests in ICH patients. Methods: 1) Out of 181 ICH patients admitted to our hospital between June 2016 and February 2017, 126 patients of hypertensive ICH were enrolled in this study. Plasma aldosterone concentration (PAC), plasma renin activity (PRA) and other hormones were measured in the morning two days after admission. 2) 1,242 hypertensive ICH patients admitted to our hospital after January 2013 were retrospectively reviewed Results: 1) After excluding those who had been taking medications which could intervene with PAC or PRA on admission, nine patients were positive for PA screening (PAC/PRA ratio &gt;200 and PAC &gt;120 pg/mL) and 46 were negative. Age (68.6 vs 67.1 y), sex (male 66.7 vs 67.3 %) and blood pressure (172/97 vs 177/100 mmHg) were similar between these two groups. Serum potassium was slightly lower in positive group on admission (3.6 vs 3.9 mmol/L; P=0.108), and the difference became more evident two days later (3.7 vs 4.0 mmol/L; P=0.042). There were no differences in other hormones including cortisol and catecholamine on day 2. PA positive patients had more severe motor or cognitive impairments (Functional independence measure 58 vs 95; P=0.015). 2) After collecting 25 clinical parameters in 1,242 hypertensive ICH patients, dimension reduction procedure using t-SNE certainly divided these patients into clusters compatible with PA screening tests. Only 4% of PA positive group showed serum potassium lower than 3.5 mmol/L on admission (sensitivity 97%), and the increase in serum potassium during the first 2 days were milder in PA positive group (P=0.001). Discussion: This is the largest study ever that investigated the clinical features of PA in ICH patients. We uncovered that transitional changes of serum potassium after the onset of ICH were efficient markers to decide who should go on to PA screening tests. ICH increases sympathetic activity and subsequent renin secretion, resulting in low serum potassium even in PA negative group. But about two days later, when its activity peaked out, serum potassium in PA negative group restores to their original states while that in PA positive group are stable due to constitutive secretion of aldosterone. Since ICH patients with PA are at higher risk for recurrent hemorrhage and other complications, diagnosis of PA is important even after the occurrence of ICH. PA screening should not be awaited just because they have developed ICH.
Vitamin D Deficiency Induces Macrophage Pro-Inflammatory Phenotype via ER Stress-Mediated Activation of Renin-Angiotensin System
Authors: Bauerle Kevin Thomas , Oh Jisu , Riek Amy Elizabeth , Dusso Adriana , Castro-Grattoni Anabel L , Gomez R Ariel , Sequeira-Lopez Maria L , Bernal-Mizrachi Carlos 
Published: May 2021

Abstract
Chronic inflammation and local activation of the renin-angiotensin-aldosterone system (RAAS) play a pivotal role in the pathogenesis and progression of diabetic complications. In patients with type 2 diabetes (T2DM), the prevalence of vitamin D deficiency is almost twice that of non-diabetics, and vitamin d deficiency nearly doubles the risk of developing hypertension and cardiovascular complications compared to diabetics with normal vitamin D levels. Interestingly, mice lacking the vitamin D receptor (VDR) in macrophages (KODMAC) develop renin-dependent hypertension, insulin resistance, and inflammation via up-regulation of macrophage ER stress. Macrophages also express all major components of the RAAS system. However, little is known about the regulation of macrophage-generated renin and its role in modulating the sequelae of VDR signaling in macrophage function and cytokine production. This study found that KODMAC macrophages and vitamin D-deficient macrophages have increased expression and secretion of renin, angiotensin II, ACE, and AT1 receptor and that adhesion, migration, and cytokine release were also increased. Inhibition of ER stress in KODMAC macrophages and vitamin D-deficient macrophages with 4-Phenylbutyric acid (PBA) reduced RAS gene expression and macrophage pro-inflammatory phenotype. Renin 1c gene deletion decreased macrophage adhesion, migration, and cytokine release compared to macrophages with disrupted VDR signaling. Notably, disruption of VDR signaling induced peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) expression in macrophages, and upregulation of renin expression in response to vitamin D deficiency was blunted in PCG1α-deficient macrophages. In conclusion, our findings delineate a mechanism by which impaired VDR signaling induces ER stress to drive PGC1α-dependent expression of renin and RAAS hyperactivation, thereby altering macrophage function and cytokine production. These data implicate RAAS as an essential mediator of VDR-mediated macrophage function and support ongoing investigations of VDR and RAAS modulation as therapeutic approaches in the management of T2DM and its complications.