bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association Between Population Vitamin D Status and SARS-CoV-2 Related Serious-Critical Illness and Deaths
Authors: Papadimitriou Dimitrios T , Vassaras Alexandros K , Holick Michael F 
Published: May 2021

Abstract
Background: Vitamin-D population status may have possible unappreciated consequences to the COVID-19 pandemic. Α significant association between vitamin-D sufficiency and reduction in clinical severity and inpatient mortality from COVID-19 disease was recently shown while a recent study has claimed lower COVID-19 cases in European countries with a better vitamin D status. Aims: To further elucidate the possible role of vitamin D population status in the COVID-19 pandemic, we examined the associations between published representative and standardized population vitamin D data on European population vitamin D status and the Worldometer COVID-19 data. Methods: Data from the Worldometer on 26 European countries populated &gt;4 million (M) were analyzed. Results: On 19-June-2020, linear regression found no correlation between published representative-standardized population vitamin-D concentrations and the total cases-recovered/M, but negative correlations predicting a reduction of 47-64-80% in serious-critical illnesses/M and of 61-82-102.4% in deaths/M, further enhanced when adapting for life expectancy by 133-177-221% if 25(OH)D concentrations reach 100-125-150 nmol/L. On 15-August-2020 these correlations were sustained indicating a truthful association, yet not proving causality. Weighted ANOVA was performed to evaluate serious-critical/M (R2=0.22) by the vitamin-D population status (deficient-D &lt;50, insufficient-IN 50–62.5, mildly insufficient-MIN &gt;62.5–75 and sufficient-S &gt;75 nmol/L) and ANCOVA the deaths/M (R2=0.629) after controlling for life expectancy (R2=0.47). Serious-critical showed a decreasing trend (p&lt;0.001) from population status D (p&lt;0.001) to IN: 9.2%, p&lt;0.001, MIN: 47.6%, p&lt;0.044 and S: 100% (reference). For deaths/M the respective decreasing trend (p&lt;0.001) was 62.9% from D (p&lt;0.001) to IN (p&lt;0.001), 65.15% to MIN (p&lt;0.001) and 78.8% to S (p=0.041). Conclusions: Following the Endocrine Society’s expert committee recommendations, without previous testing being necessary, reaching and maintaining a serum 25(OH)D of 100–150 nmol/L (40–60 ng/ml) could be achieved by an initial supplementation with the upper tolerable daily intake doses (IU/day) for up to two months: &lt;1yr 2000, 1-18yrs 4000 and all adults 10,000 (obese x 2–3 times more) and then with the maintenance proposed doses that do not require medical supervision, practically identical with the IOM’s upper tolerable limits: 1000 &lt;6m, 1500 6m-1yr, 2500 1-3yrs, 3000 4-8yrs, and 4000 &gt;8yrs, with adults and adolescents requiring 4000–5000 (obese x 2). Vitamin D may not prevent SARS-CoV-2 from spreading but may protect, without any risk of toxicity, from serious-critical illness and death from COVID-19 disease. While awaiting well-designed prospective studies, following the proposed approach, the gain for global public health and not only against SARS-CoV-2 may just prove invaluable.
Increasing Pediatric Hospitalizations With Severe Vitamin D Deficiency: A Concerning Trend
Authors: Carlton Jared , Lahoti Amit 
Published: May 2021

Abstract
Background: Deficiency of vitamin D can lead to multiple health issues in children. Though it can be asymptomatic in early stages, it can lead to symptomatic illnesses if severe/ prolonged including seizures and rickets. Deficiency can be prevented by adequate dietary vitamin D intake with/without supplementation in those at higher risk. However, there has been a recent reemergence and increase in the incidence of vitamin D deficiency in European nations, noted as early as 2008 and at least upto 2018. Hence, we performed a 10 year retrospective study of severe vitamin D deficiency in hospitalized patients at a Children’s Hospital in USA.
Methods: Electronic medical record was searched to identify patients with the following inclusion criteria: admitted at our hospital between 1/1/2010 and 12/31/2019 and had a 25-OH vitamin D (25-OH D) level &lt;13 ng/mL with/without hypocalcemia or had a diagnosis of rickets. The study was approved by our institutional review board and consent was waived. Patient demographics, medical history and data on laboratory results, treatment given were extracted. We then ran a summative analysis of most of the data collected, analyzed trends for the number of admissions per year and the response time of calcium levels.
Results: Between 1/1/2010 and 12/31/2019, there were 109 hospital admissions with 25-OH D deficiency with or without hypocalcemia. Median 25-OH D level was 9.7 ng/mL. Admissions per year increased from 2010 to 2019 as follows: 2 in 2010, 5 in 2011, 4 in 2012, 6 in 2013, 6 in 2014, 7 in 2015, 12 in 2016, 13 in 2017, 23 in 2018, 25 in 2019. Median patient age was 27 months (range 0,228). Of those &lt;/=1 year (n=39), 13% were preterm, 38% were exclusively breastfed and 44% were formula fed. Ninety percent of these infants were not receiving vitamin D supplementation prior to hospitalization. Of the entire cohort of 109 patients, 63% were males and race distribution was as follows: 13% were White, 77% were Blacks and 10% were others. Seventy percent patients were on state sponsored insurance. About 33% had some diet restrictions/ peculiarities, 40% had a presenting complaint related to hypocalcemia including seizures, while 44% had hypocalcemia but it was not their primary reason for presentation. Seventy eight percent patients had hypocalcemia. Of the patients with initial calcium &lt;7.5 mg/dL (n=64), it took a median of 72 hours (range 7,468) to improve to &gt;/= 7.5 mg/dL.
Conclusions: Our hospital has witnessed a significant increase in severe vitamin D deficiency in admitted patients between 2010 and 2019. A large proportion of these were Blacks, on state sponsored insurances and infants not on vitamin D supplementation. Greater than 3/4th of patients had hypocalcemia and over 50% patients had hypocalcemia that required a median of 3 days to correct. This is a concerning trend of an often easily preventable morbidity and another health issue that highlights disparities in our health system.
Lack of Association Between 25-Hydroxyvitamin D Level and Outcomes in Hospitalized Indian Patients With COVID-19
Authors: Jevalikar Ganesh , Sharma Rutuja , Farooqui Khalid J , Singh Anshu , Budhiraja Sandeep , Dewan Arun , Mithal Ambrish 
Published: May 2021

Abstract
Vitamin D deficiency (VDD) is thought to play a role in determining the outcomes of COVID-19. India has a high prevalence of VDD. We hypothesized that VDD as measured by serum 25-hydroxyvitamin D (25OHD) &lt;20 ng/mL is associated with severe COVID-19 infection. Outcomes were assessed by the WHO ordinal scale for clinical improvement (OSCI)1, the need for oxygen therapy, admission to an intensive care unit (ICU), and inflammatory markers. The diagnosis of COVID-19 was proven by RT-PCR on the nasopharyngeal swab for SARS-CoV2. Serum 25OHD and PTH were measured in addition to the standard protocol for COVID-19. Clinical and laboratory data were extracted from electronic medical records and analyzed using SPSS v22.0. Patients with OSCI score &lt; 5 were classified as mild and ≥5 as severe disease. The study was approved by the Institutional Ethics Committee. A total of 410 patients (127 females, 9 pediatric, 17 asymptomatic) were included with a median age of 54 years (6–92 years) with 272(66.3%) having at least one co-morbid condition, including diabetes (190, 46.3%) and hypertension (164,40%). Patients with VDD (197,48%) were significantly younger (46.7±17.1 vs. 57.8±14.7 years) and had lesser prevalence of diabetes and hypertension (39.1% vs 52.4%, 29.4% vs 49.5%). Proportion of severe cases (26,13.2% vs. 31,14.6%), mortality (4, 2% vs. 11, 5.2%), oxygen requirement (68,34.5% vs.92,43.4), ICU admission (29, 14.7% vs. 42, 19.8%), need for inotropes (7,3.6% vs.12,5.7%) was not significantly different between patients with VDD and those with normal 25OHD level. The proportion of severe cases was similar across all 25OHD categories. There was no significant correlation between 25OHD levels and outcome OSCI, inflammatory markers (CRP, IL-6, D-dimer, ferritin, LDH). PTH levels positively correlated with D-dimer (r 0.117, p- 0.019), ferritin (r 0.132, p-0.010) and LDH (r0.124, p-0.018). Amongst VDD patients, 128(64.9%) were treated with cholecalciferol with a median dose of 60000 IU. The proportion of severe cases, oxygen, or ICU admission was not significantly different in the treated vs. untreated group. In conclusion, baseline levels of 25OHD did not determine the severe clinical outcomes of COVID-19 or levels of inflammatory markers. Treatment with cholecalciferol did not make any difference to the clinical outcomes of those with VDD. Reference:1WHO R&D Blueprint, novel Coronavirus. Retrieved from: https://www.who.int/blueprint/priority-diseases/key-action/COVID-19_Treatment_Trial_Design_Master_Protocol_synopsis_Final_18022020.pdf
The Impact of Glucose Tolerance States on Bone Mineral Density and Fracture Rate
Authors: Villacreses Maria Chang , Panjawatanan Panadeekarn , Karnchanasorn Rudruidee , Ou Horng-Yih , Feng Wei , Samoa Raynald , Chuang Lee-Ming , Chiu Ken C 
Published: May 2021

Abstract
It is generally acknowledged that fracture rate is higher in diabetic subjects than non-diabetic subjects. However, the impact of diabetes on bone is less clear due to contradictory results of bone mineral density (BMD) and fracture rate. To date, most of reports were based on the studies from relatively small sample sizes. To clarify the issues, we examined the fracture rates and BMD across a spectrum of glucose tolerance in a representative US population.
The participants of the National Health and Nutrition Survey 2005–2010 were used in this study. Among adult subjects (age≥20 years old) with reported BMI, we were able to define the states of glucose tolerance in 31,073 subjects cording to the diagnostic criteria based on HbA1c, fasting glucose, and/or 2-h post-changed glucose with established diabetes and using diabetes medications, into normal glucose tolerance (NGT), abnormal glucose tolerance (AGT), and diabetes mellitus (DM). Those who received osteoporosis medications were excluded from BMD analysis. Fracture information was available in 15,547 subjects; validated hip BMD was available in 12,317 subjects; and validated lumbar spine BMD was available in 10,329 subjects. Fracture rates were compared among 3 groups of glucose tolerance states and odds ratio (OR) with 95% confidence intervals (95% CI) were calculated in reference to the NGT group with sample weighting. BMD was compared among 3 groups of glucose tolerance with consideration of covariates.
The reported osteoporosis diagnosed rate differed among 3 groups of glucose tolerances (3.99%, 5.77%, and 8.41%, P&lt;0.001, for NGT, AGT, and DM respectively). Worsening states of glucose tolerance were associated increased fracture OR at Hip [AGT, 2.1770 (95% CI: 2.1732–2.1807) and DM, 2.7369 (95% CI: 2.7315–2.7423)], spine [AGT, 0.9924 (95% CI: 0.9912–0.9936); DM, 1.2405 (95% CI: 1.2387–1.2423)]. In contrast, a different trend was observed on the wrist fracture rate [AGT, 0.9556 (95% CI: 0.9551–0.9562); DM, 0.9053 (95% CI: 0.9045–0.9060)]. After adjustment for covariates, higher BMD was noted in AGT and DM when compared to NGT at total femur (NGT, 0.9760±0.0015 gm/cm2; AGT, 0.9853±0.0021 gm/cm2; DM 0.9847±0.0034 gm/cm2, mean±SE, P=0.001) and femoral neck (NGT, 0.8388±0.0015 gm/cm2; AGT, 0.8474±0.0020 gm/cm2; DM, 0.8496±0.0032 gm/cm2, P=0.0007) while no difference was found in lumbar spine BMD (NGT, 0.1.0441±0.0018 gm/cm2; AGT, 1.0406±0.0025 gm/cm2; DM, 1.0464±0.0041 gm/cm2, P=0.35).
Our observed significant increased fracture risk at hip (OR: 2.7369) and lumbar spine (OR: 1.2405) in DM subjects when compared to NGT subjects. DM subjects had higher BMD at total femur and femoral neck than NGT subjects while no difference was noted at lumbar spine BMD when compared to NGT subjects. Further studies are required to explore the discrepancy between the increased fracture risk with higher BMDs in diabetes.
Association Between Thyroid Hormones and Lipids Stratified by Race and Sex
Authors: Shakoor Musa , Ahmad Zahid 
Published: May 2021

Abstract
It has been well-established that thyroid hormones play a role in cholesterol and lipoprotein metabolism. However, there is limited data assessing the variability in the association between thyroid hormones and lipids across sex and race. We hypothesized that thyroid dysfunction is associated with changes in lipids and lipoproteins with no substantial variability in this association between races and sex. The electronic medical record of a large county hospital in Dallas, TX was queried to obtain data on all patients who had lipid panels and thyroid function tests checked on the same day from 1/1/2013 to 1/1/2018. The results were stratified into hypothyroid (TSH greater than 4.5 mcIU/L and Free T4 less than 0.8 ng/dL), hyperthyroid (TSH less than 0.5 mcIU/L and Free T4 greater than 1.8 ng/dL) and normal (TSH between 0.5 and 4.5 mcIU/L, Free T4 between 0.8 and 1.8 ng/dL). Results consistent with subclinical thyroid disease were excluded from further analysis. There were 25,290 unique results for thyroid hormones and lipid panels checked on the same day. The results were further stratified by race and sex, and the relationship between thyroid function and lipids was assessed. The correlation coefficient (r) was compared between sexes within each race for the following variables: TSH vs HDL-C, TSH vs LDL-C, TSH vs Total Cholesterol, TSH vs triglycerides, FT4 vs HDL-C, FT4 vs LDL-C, FT4 vs Total Cholesterol, and FT4 vs triglycerides. Among black males with hypothyroidism, there was a notably stronger correlation when compared to black females in the relationship between TSH vs LDL-C, and TSH vs Total Cholesterol. Specifically, the correlation coefficient of TSH vs LDL-C among Black males with hypothyroidism was 0.582, compared to 0.133 among Black females with hypothyroidism (P=0.0053). Furthermore, the correlation coefficient of TSH vs Total Cholesterol among Black males was 0.567 compared to 0.184 among Black females (P=0.016). In contrast, no difference in any of the relationships between thyroid and lipids was demonstrated between sexes amongst Whites, Asians, and Hispanics. Overall, we found differences in Black patients compared to patients of other races with regards to the association between thyroid and lipids. Specifically, it was found that Black males with hypothyroidism had a stronger positive correlation in TSH vs LDL-C and TSH vs Total Cholesterol than Black females. This type of difference between sexes was not found amongst any other race. These findings suggest that thyroid dysfunction is associated with changes in lipids, and the way these changes manifest may vary depending on the race and sex. This further highlights the importance of checking lipid panels in patients with thyroid dysfunction. Further research is needed to more clearly characterize the variation that is seen in thyroid and lipid function amongst races.
Exploring Cardio-Metabolic Effects of Liraglutide in Patients With Type 2 Diabetes Through a Proteomic Approach
Authors: Ekhzaimy Aishah Ali , Masood Afshan , Benabdelkamel Hicham , Elhassan Tasnem , Alfadda Assim A 
Published: May 2021

Abstract
Background: Diabetes is associated with complications that increase the risk of cardiovascular events in diabetic patients by 3 folds compared to healthy population. Liraglutide is a GLP-1 receptors agonist that showed cardiovascular benefits beside its glycemic advantage and weight reduction. The cardioprotective benefit of liraglutide in diabetic patients is unclear. Objective: To explore potential cardiovascular-protective and metabolic effects of Liraglutide treatment in patients with T2DM, through evaluation of alterations in circulatory proteins using a proteomics approach. To relate the altered proteins to identify pathways using bioinformatics and network pathway analysis. Methods: Twenty adult patients with T2DM were recruited with HbA1c of 8–11 %, on oral anti-diabetic agents or insulin in whom liraglutide was indicated, after obtaining the consent. At baseline: anthropometric measurements, basal blood for HBA1c, Renal function, creatinine clearance, lipid profile and urine in the fasting state. Then Liraglutide 1.8 mg subcutaneous once daily injection was initiated as prescribed by the treating physician. AT 3 months follow up visit post-treatment, similar parameters were measured. Primary endpoint was the reduction from baseline in HbA1c for ≥ 0.5 %. Results: Alterations in the abundance of urinary proteins, analyzed by Progenesis software, revealed statistically significant differential abundance in a total of 80 spots corresponding to 71 proteins, 14 up and 57 down (≥1.5-fold change, ANOVA, p ≤ 0.05) in the post treatment group. The proteins identified in our study are known to regulate processes related to acute phase response (APR), cellular metabolism and transport. The post treatment group demonstrated an increased abundance of proteins that included alpha-1-antitrypsin, alpha-1-antichymotrypsin, serotransferrin, transthyretin, plasma protease C1 inhibitor, adenosylhomocysteinase 3 and beta-2-glycoprotein 1. The proteins with a decrease in abundance following treatment included transthyretin, serotransferrin, haptoglobin, complement C3, retinol binding protein and ceruloplasmin. Bioinformatic analysis using Ingenuity Pathway Analysis (IPA) identified dysregulation of pathways related cellular compromise, inflammatory response, and neurological disease. It also identified the involvement of the inflammatory signalling pathways, NFκb, AKT, p38 MAPK via their interactions with interleukin 12 as the central nodes.
Conclusion: The altered proteins identified in the present study showed an increase in the APR in patients with diabetes before treatment with liraglutide which was significantly reduced in the post treatment group. Increase in the APR is known to lead to a state of chronic inflammation predisposing individuals to cardiometabolic stress and disease.
Patients With Obesity-Related Hypertension Treated With Renin-Angiotensin-Aldosterone System Antagonists Exhibit Lower Mortality And Less Severe COVID-19: A Retrospective Study
Authors: Kamalumpundi Vijayvardhan , Shams Elham , Cheng Linhai , Taiwo Adeyinka , Shibli-Rahhal Amal A , Dokun Ayotunde O , Correia Marcelo 
Published: May 2021

Abstract
Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been found to exploit the cell’s ACE2 receptor for viral entry. Renin-angiotensin-aldosterone system (RAAS) antagonism with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) increases the expression of ACE2 receptors which, coupled with the metabolic changes associated with obesity-related hypertension, can make hypertensive patients with obesity more vulnerable to severe COVID-19. Although current evidence suggests that ACEI/ARB use does not increase risk of severe COVID-19 in the general population, potential interactions with obesity-related hypertension are unknown. Methods: We conducted a retrospective study of COVID-19 patients admitted to the University of Iowa Hospitals and Clinics between March 1st and July 8th, 2020. We included adults who are overweight (BMI ≥ 25 kg/m2) or obese (BMI ≥ 30 kg/m2) with hypertension treated as outpatients with or without ACEIs/ARBs. Patients without exposure to RAAS antagonists served as controls. We assessed mortality and the severity of COVID-19 reflected by admission to ICU and usage of supplemental O2, non-invasive ventilation, mechanical ventilation, extracorporeal membrane oxygenation (ECMO) and vasopressors. Results: Of the 369 inpatients with COVID-19, we identified 138 exhibiting obesity-related hypertension who were then allocated into the control (n=59) and ACEI/ARB (n=79) groups. The BMIs between groups at baseline were not statistically significant (Control: 33.6 ± 0.96 vs. ACEI/ARB: 34.99 ± 0.97; p=.32). Women were less represented in the ACEI/ARB group (Control: 47% vs. ACEI/ARB: 24%). The controls had a substantially higher mortality rate (Control: 32.2% vs. ACEI/ARB: 15.1%). In regard to the severity of COVID-19, the ACEI/ARB cohort showed lower usage of supplemental O2 (Control: 52.5% vs. ACEI/ARB: 49.3%), mechanical ventilation (Control: 37.2% vs. ACEI/ARB: 1.2%), vasopressors (Control: 38.9% vs. ACEI/ARB: 31.6%), and had lower ICU admissions (Control: 57.6% vs. ACEI/ARB: 46.8%). However, the ACEI/ARB group had higher rates of: ECMO (Control: 0% vs. ACEI/ARB: 20.2%) and non-invasive ventilation (Control: 18.6% vs. ACEI/ARB: 20.2%). Of note, the rate of diabetes was higher in the ACEI/ARB cohort (Control: 45.7% vs. ACEI/ARB: 63.2%). Conclusion: Our results suggest that a history of RAAS antagonism is associated with lower mortality and less severity of COVID-19 in patients with obesity-related hypertension requiring hospital admission.
Re-Evaluating Absent Clinical Success After Adrenalectomy in Unilateral Primary Aldosteronism
Authors: Puar Troy , Chan Yvonne , Loh Lih-Ming , Foo Roger , Kek Peng Chin 
Published: May 2021

Abstract
Introduction: Adrenalectomy cures unilateral primary aldosteronism (PA), and improves or cures hypertension. However, a significant proportion of patients are classified with absent clinical success post-surgery, suggesting that surgery was ineffective. Methods: We assessed all patients 6–12 months after unilateral adrenalectomy for clinical outcomes using Primary Aldosteronism Surgical Outcomes (PASO), AVIS-2 and CONNsortium criteria. We estimated blood pressure (BP) changes after adjustment for changes in defined daily dosages (DDD) of antihypertensive medications. Finally, patients were reassessed using PASO at their most recent clinical visit. Results: 104 patients with unilateral PA underwent adrenalectomy at two tertiary centres from 2000–2019. 24 (23%), 31(30%) and 54 (52%) patients were classified with absent clinical success using PASO, AVIS-2 and CONNsortium criteria respectively. Amongst 24 patients with absent clinical success using PASO criteria, 10 had complete biochemical cure, 3 partial, 2 absent, and 9 had resolution of hypokalemia. On multivariate analysis, absent clinical success was associated with presence of hyperlipidemia, diabetes mellitus and lower DDD at baseline. After adjustment for changes in DDD, 7 of 24 patients showed BP improvement ≥20/10mmHg. After follow-up of mean 5.6 years, 12 of 24 patients showed partial or complete clinical success when reassessed using PASO criteria. Only 6 of 104 (5.8%) patients failed to show any clinical improvement after surgery. Conclusions: Although some patients may be classified with absent clinical success post-surgery, majority demonstrate evidence of clinical benefit. Unilateral adrenalectomy remains the recommended treatment option for patients with unilateral PA.