bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic Accuracy of Different Screening Tools for Identifying Osteoporosis Risk Among Post-Menopausal Filipino Women Aged 45–65 Years
Authors: Alcantara Danga Justiene Mia Klarisse , Lim Steven Johnson , Sulit Jacquelyn , Pacheco Elizabeth P
Published: May 2021

Early screening of osteoporosis decreases fracture risk. Several identified clinical risk factors led to the development of screening tools to estimate osteoporosis risk. Bone Mineral Densitometry (BMD) as a diagnostic tool for screening is not practical because of high cost and poor availability. The extensively studied osteoporosis screening tools are: Simple Calculated Osteoporosis Risk Estimation (SCORE), the Osteoporosis Risk Assessment Instrument (ORAI), the Age Bulk One or Never Estrogen (ABONE), body weight (WEIGHT), and the Osteoporosis Risk Index (OSIRIS). These tools were developed and validated in Caucasians. Validation of these tools for specific populations is necessary because of the observed variations in BMD across geographic and ethnic groups. To date, the utility of these screening tools in the Philippines is unknown. We conducted a cross-sectional analysis of all patients who underwent BMD screening for osteoporosis in a tertiary hospital from January 2015 to September 2020. The study participants were postmenopausal Filipino women aged 45 to 65 years. The subjects had no history of osteopenia, osteoporosis, hip or spine fractures, use of osteoporosis medications, renal insufficiency, bilateral oophorectomy, hysterectomy, or early menopause. We identified demographic and clinical risk factors. These risk factors were used to calculate the risk score of five osteoporosis risk assessment tools: ORAI, ABONE, WEIGHT, OSTA, and ORISIS. Using the DEXA T-score as an external criterion, the sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and diagnostic accuracy for each tool were calculated. Included were 1869 subjects with a mean age of 57.9 + 4.3 years old. Osteoporosis, with a T-score of <-2.5 at the lumbar or femoral neck area, was seen in 665 (35.58%). Risk factors such as weight, height, BMI, menopausal years, history of previous fractures, and intake of oral calcium supplements correlated significantly with a higher risk (OR=1.025, 95%CI: 0.974–1.079; OR=1.059, 95%CI: 0.84–1.338; OR=1.063, 95%CI: 0.817–1.383; OR=1.74, 95%CI: 1.198–2.528; and OR=1.088, 95%CI: 0.869–1.319), of having osteoporosis in the said population. ORAI and WEIGHT have the highest probability of identifying patients with a sensitivity of 88.42% and 91.28%, and accuracy of 85.71% and 87.98%. Both performed equally in screening for osteoporosis in this setting. However, ABONE, OSTA, and ORISIS underestimated the number of high-risk osteoporosis patients, because of their low sensitivity and diagnostic accuracy. Both ORAI and WEIGHT are simple and easy to calculate and can serve as an initial screening tool to identify Filipino postmenopausal women who are at high risk for osteoporosis. A prospective study with a correlation of fracture occurrences may provide evidence for the value of these tools as a screening test.
Factors Associated With Inadequate Response to Bisphosphonate Therapy in Patients With Osteoporosis in Real-Life Clinical Practice: a Single-Center Retrospective Analysis of 300 Patients
Authors: Valadares Luciana Pinto , de Araujo Ferreira Bruno Silva , Cunha Bernardo Matos , Moreira Larissa Aniceto , Albinati Batista Frederico Gideoni , Hottz Cristiane Fonseca , Rafael Magalhaes Gabriel Galvao , Rodolpho Ramalho Sergio Henrique
Published: May 2021

Introduction: Bone mineral density (BMD) measurement by dual X-ray absorptiometry (DXA) is a useful tool to monitor response to osteoporosis treatment in clinical practice. Despite bisphosphonates therapy, some patients may exhibit bone loss during treatment for different reasons. These patients may have greater fracture risk than responders and may have unrecognized secondary causes that require further attention and treatment. Objectives: To identify factors associated with inadequate response (IR) to bisphosphonates therapy in patients with osteoporosis in real-life clinical practice. Methods: This is a single-center case-control study of patients with osteoporosis treated with bisphosphonates as recommended. Baseline and follow-up (12–24 months/apart) DXA scans were performed on same device (GE-Lunar Prodigy). IR was defined as loss of BMD greater than the least significant change (LSC) on the follow-up DXA. Clinical, biochemical and densitometric parameters of patients with IR were compared to responders using t-test or Mann-Whitney test (continuous), or chi-square test (categorical variables), as appropriated. We used logistic regression to assess the association magnitude between exposures and IR. Results: From 300 patients included from 2014 to 2018 (13% males, mean age 68 ±10 years), 198(66%) were treated with oral bisphosphonates and 102(34%) with zoledronic acid (ZA). IR was observed in 44(15%) patients. All parameters were similar at baseline, except for greater prevalence of oral bisphosphonates (82% vs 63%, p=0.016) and anticonvulsants use (18% vs 7%, p=0.015) in patients with IR compared to responders. Additionally, patients with IR exhibited a lower % change in CTX following therapy in comparison to responders (median -37% [IQR -68; -16%] vs -57% [-74; -32], p=0.029, respectively), and higher serum CTX levels after treatment (median 236pg/mL [IQR 162; 344] vs 165pg/mL [119; 254], p=0.004). The likelihood of IR was greater with oral bisphosphonates then with ZA (OR 2.61, IC95% 1.16–5.81, p=0.002), and with anticonvulsants use (OR 2.94. IC95% 1.19–7.25, p=0.019). The association with IR persisted for both variables (p≤0.01), when accounted simultaneously in the same model, along with age and gender. Conclusion: Inadequate bisphosphonate response was present in 15% of individuals, which was independently associated with anticonvulsant use and particularly among those on oral bisphosphonate therapy rather than ZA. This knowledge may help to clinically identify potential modifiable factors related to unresponsiveness and to optimize treatment accordingly.
Impact of Measuring Bone Mineral Density at Bilateral Hip
Authors: Singh Abhilasha , Sharma Anu
Published: May 2021

Osteoporosis is a systemic disease characterized by low bone mineral density (BMD) leading to an increased risk of fracture. The current guidelines vary regarding the measurement of BMD at unilateral versus bilateral hip. We hypothesized that a discordance exists between bone densities measured at both hips and that patients undergoing unilateral hip imaging are at risk for under diagnosis. A retrospective chart review was performed to include all patients age 18 years and older, who underwent bone density measurement in 2019 at a single center using Hologic densitometer. Data gathering included BMD and T- scores at bilateral hip for all postmenopausal women and men above the age of 50 yrs. The continuous variables were expressed as means with standard deviation for normal distribution and analyzed with a two-sample t-test. Multiple regression analysis was used to test the effect of underlying medical conditions on T-score at bilateral hips. For all analyses, a p-value of <0.05 was considered significant. 150 patients were included in the study (127 females and 23 males) with a mean age at imaging of 65.2 + 9.7 years and body mass index (BMI) of 27.2 + 6.1 kg/m2. 9% (n=14) of patients were observed to have discordance between T scores at both hips, out of which 13 individuals would have been underdiagnosed if one side was measured alone. There was a significant difference between mean BMD at total hip (left hip 0.84 + 0.14 g/cm2 vs right hip 0.82 + 0.14 g/cm2; p<0.05). Among individuals with discordant T scores, a positive correlation was observed with BMI at the left femoral neck (r= 0.54, p= 0.04). Results: of multiple regression analysis showed that 67% of variation in the T score at right femoral neck could be accounted for by underlying medical conditions. Appointment duration and cost were unchanged when scanning unilateral or bilateral hip, 30 minutes, and $250 respectively. In summary, scanning bilateral hips provides treatment opportunities for patients who would otherwise be underdiagnosed without an additional increase in cost.
Use Machine Learning Methods to Explore the Associated Risk Factors of Osteoporosis or Bone Loss in Chinese People With Type 2 Diabetes: A Clinical Prediction Model
Authors: Mao Yaqian , Liang Jixing , Lin Wei , Wen Junping , Chen Gang
Published: May 2021

Objective: This study aimed to use machine learning (ML) methods to explore the risk factors associated with OP and bone loss in the Chinese T2DM population, so as to construct useful clinical prediction models. Methods: This was a two-center, retrospective study. The data came from a chronic disease epidemiological investigation database conducted in Ningde City and Wuyishan City, Fujian Province, China from March 2011 to December 2014. Finally, 798 T2DM patients who met the enrollment criteria were included in the final analysis. In order to control gender as a confounding factor that affects the results, we constructed two clinical prediction models based on different genders. We used the least absolute shrinkage and selection operator (LASSO) algorithm to filter relevant feature variables. The selected characteristic variables were modeled by logistic regression (LR), and clinical nomograms were used for more intuitive expression. The stability, clinical applicability and recognition of the model were evaluated by C-index, receiver operating characteristic (ROC) curve, calibration chart and decision curve analysis (DCA). Internal verification was achieved through bootstrapping validation. Results: In exploring the related risk factors of OP or bone loss in female T2DM patients. There were a total of 9 related predictors, namely age, marital status, glutamyl transpeptidase, fracture, coronary heart disease, fruit-flavored drinks, moderate-intensity exercise, menopause and nap time were determined by LASSO analysis from a total of 69 variables. The model we constructed using these 9 related predictors showed medium prediction ability (C-index value: 0.738, 95%CI[0.692, 0.784]), the C-index in bootstrapping validation was 0.714, and the area under the ROC curve (AUC) was 0.738. The DCA showed that if the risk threshold was between 4% and 100%, the nomogram could be used clinically. In exploring the related risk factors of OP and bone loss in male T2DM patients. A total of 12 related predictors were identified from 65 variables through LASSO analysis, including age, marital status, fasting serum insulin, alanine aminotransferase, coronary heart disease, respiratory diseases, diabetic retinopathy, seafood, desserts, fruit-flavored beverages, coffee, high-intensity exercise. The model we constructed using these 12 related predictors showed medium prediction ability (C-index value: 0.751, 95%CI[0.694–0.808]), the C-index in bootstrapping validation was 0.704, and the AUC value was 0.751. The DCA showed that if the risk threshold was between 3% and 68%, the nomogram could be used clinically. Conclusion: We explored the associated risk factors of osteoporosis or bone Loss in Chinese people with type 2 diabetes, and developed a risk nomogram with moderate predictive power. The nomogram can help clinicians and patients make joint decisions before treatment.
Assessment of Hypercalcemia Management at an Academic Institution
Authors: Nagelberg Jodi , Hakim Robert , Kimura Brad , McCowen Karen C , Block Shanna
Published: May 2021

Background: Currently, there is no widely accepted clinical practice guideline for the management of severe hypercalcemia in hospitalized patients.

Objective: The purpose of this project was to analyze management of hypercalcemia in hospitalized patients at an academic medical center, then establish and implement a clinical practice guideline for hypercalcemia treatment.

Design: Retrospective chart review of all patients admitted for management of hypercalcemia over 37 consecutive months.

Setting: Urban academic tertiary referral center

Measurements: We examined which calcium- lowering medications were used, how often 2 medications were needed, average time to normocalcemia, incidence of hypocalcemia post treatment, serum phosphorus nadir and serum creatinine peak. We also assessed medication appropriateness (dose and frequency).

Results: Seventy-two patients were included; 58 patients with hypercalcemia of malignancy and 14 patients with hypercalcemia of other diagnoses. In the malignancy group the most common treatment was a combination of calcitonin + bisphosphonate (43%), followed by bisphosphonate alone (29%) and calcitonin alone (24%). In the non-malignancy group, calcitonin alone was used in 50%, calcitonin + bisphosphonate in 21% and a bisphosphonate alone in 14%. Denosumab was rarely used in both groups. The median time to normocalcemia was 3.0 days irrespective of diagnostic group. Seventy two percent of the patients with malignancy and 86% of the non-malignancy group achieved normocalcemia. The incidence of hypocalcemia was 21% (12/58) in the malignancy subgroup and 29% (4/14) in the others after treatment. Serum creatinine did not change from baseline to post-treatment in either population. Median serum phosphorus dropped from 2.9 mg/dL to 1.8 mg/dL in the malignancy group and 4.2 mg/dL to 2.1 mg/dL in the non-malignancy group. Only 41% of patients that received calcitonin, were given recommended dose, route, and frequency.

Conclusion: Based on the results of this study, a hypercalcemia treatment guideline was developed, highlighting appropriate medication dose and frequency. This guideline recommends zoledronic acid alone for asymptomatic malignancy patients, and in combination with calcitonin for symptomatic patients. In contrast, calcitonin alone is considered first line for non-malignant conditions.
Rare Case of Severe Hypercalcemia Secondary to Atypical Sestamibi Negative Parathyroid Cystic Adenoma
Authors: Gusov Timur , Liu John Chen , Naha Sowjanya , Marium F N U , Parimi Joseph Theressa Nehu , Gundluru Rajani , Syed Hasan
Published: May 2021

Primary hyperparathyroidism (PHPT) is defined as excessive secretion of parathyroid hormone (PTH) originating from the parathyroid gland. The most common cause is a single parathyroid adenoma which is typically solid. Cystic parathyroid adenomas (CPA) are the cause of about 1–2% of cases of primary hyperparathyroidism. It is known that cystic parathyroid adenomas are a result of degeneration of an existing parathyroid adenoma. SestaMIBI is an imaging study based on uptake of radioactive technetium99 and used to localize parathyroid adenomas. We describe an unusual case of severe hypercalcemia secondary to 99mTc sestaMIBI negative atypical parathyroid cystic adenoma. A 56-year-old male presented to our facility with nausea and vomiting. His past medical history included hypertension and hepatitis C with no history of fractures or kidney disease. Physical examination was normal. Upon admission the patient was afebrile with blood pressure of 170/120 mmHg and heart rate of 62 bpm. Chemistry showed Calcium of 14.5 mg/dL (8.6–10.2mg/dL), phosphorus 2.2 (2.7–4.5) mh/dL, magnesium 1.8 (1.7–2.6)mg/dL, intact PTH of 375 (15–65) pg/mL, PTH-related peptide <2.0 pmol/L(<2 pmol/L), 25-OH vitamin D of 19 ng/ml (30–80), Creatinine 1.22 (0.7–1.2)mg/dL, alkaline phosphatase 95 (40–129) units/L. He was started on aggressive hydration, calcitonin 4 units/kg, 4 mg of IV Zolendroninc acid. Neck sonogram revealed a large, complex, predominantly anechoic lesion with solid vascular components and thick internal septations in the inferior and medial aspect of the right thyroid lobe measuring 3 x 2 x 5.5 cm. Findings were confirmed with CT of the neck. Since Sestamibi scan (planar and SPECT/CT) did not show uptake in parathyroid glands, the cyst was thought to be of thyroid origin. Fine needle aspiration was not able to detect cellular material, but PTH was >100 pg/ml on the FNA sample. Otolaryngology service was consulted for parathyroidectomy. During the surgical treatment, the right upper parathyroid gland was removed with no changes in serum PTH. Next, the cystic lesion was removed with normalization of serum PTH (from 218 pg/ml to 35.2 pg/ml respectively). Intraoperative frozen section analysis was read as a cystic parathyroid adenoma. The final pathology report revealed cystic parathyroid tissue favoring parathyroid adenoma with focal atypia. Hypercalcemia resolved. Conclusions: Atypical cystic parathyroid adenomas are a rare cause of PHPT. 90% of parathyroid cysts are nonfunctional. Above mention is a case of a patient presenting with hypercalcemic crisis secondary to cystic parathyroid adenoma, which posed a diagnostic challenge as both neck ultrasound and 99mTc sestaMIBI scan were inconclusive. These findings should trigger suspicion for functional parathyroid lesions. Cystic components should be evaluated for PTH levels and if significantly elevated should be treated as a parathyroid adenoma.
The Calcium-Sensing Receptor (CaSR) Variants at rs1801725 Increase the Risk of Developing Secondary Malignant Cancers
Authors: Beasley Heather K , Actkins Ky’Era , Annika Faucon , Davis Lea , Sakwe Amos M
Published: May 2021

The dysregulation of systemic calcium homeostasis during malignancy is common in most patients with high-grade tumors. The associated comorbidity is known as cancer-induced hypercalcemia (CIH) which affects up to 30% of cases, in the absence of metastasis. In the course of breast cancer progression, the secretion of parathyroid hormone-related protein (PTHrP) by tumor cells and the associated destruction of bone tissues, leads to a progressive increase in systemic calcium or CIH. The increase in circulating Ca2+ is sensed by the calcium-sensing receptor (CaSR), which plays a significant role in maintaining Ca2+ homeostasis. More than 200 mutations and single nucleotide polymorphisms (SNPs) in the CaSR gene have been described, including the A986S CaSR at rs1801725 and Q1011E CaSR at rs1801726 SNPs with reduced sensitivity to Ca2+. Interestingly, high circulating Ca2+ is associated with aggressive breast tumors in premenopausal women and larger tumors in postmenopausal women; however, the contribution of the CaSR in breast cancer progression remains poorly understood. Unlike SNPs at rs1801726, up to 20% of breast cancer patients with SNPs at rs1801725 may be predisposed to higher circulating Ca2+ in the course of their disease. Since breast cancer frequently metastasizes to Ca2+ rich skeletal tissues, we hypothesize that the development of CIH and subsequent desensitization of the CaSR by sustained high Ca2+ is critical for both the adaptation of TNBC cells to CIH in Ca2+ rich microenvironments and TNBC progression. Our preliminary data reveal that the expression level and mutational status of the CaSR is cell type-specific, and that sustained high Ca2+ desensitizes the receptor, but promotes tumor cell growth and motility. Sustained high Ca2+ also triggers the expression of metastasis promoting genes, including the cancer/testis antigen, MAGEC2, and Plasminogen Activator Inhibitor, PAI-2, potentially via the early response genes FOS/FOSB. In addition, our preliminary data show that the A986S SNP is associated with hypercalcemia, secondary malignancy of bone and respiratory organs, and deficiency of humoral immunity. This study provides novel insights into not only the adaptation of TNBC cells to high circulating Ca2+, but also suggests that mutations of the CaSR at rs1801725 are predictive of the likelihood for metastasis to lungs and bone.
Circulating Lipocalin-2 Predicts Changes in Lumbar Spine Bone Mineral Density After Parathyroidectomy in Primary Hyperparathyroidism
Authors: Lee Seunghyun , Hong Namki , Kim Kyoung Jin , Jeong Jong Ju , Rhee Yumie
Published: May 2021

Lipocalin-2(LCN2), known as neutrophil gelatinase-associated lipocalin is known to a regulator of bone homeostasis. Upregulation of LCN2 in mice reduces osteoblast differentiation and stimulates the NF-kB pathway, promoting osteoclastogenesis. High serum LCN2 level was associated with elevated risk of fracture-related hospitalization in elderly women. Bone mineral density(BMD) of primary hyperparathyroidism(PHPT) patients tends to recover after parathyroidectomy, but with different extent. Whether circulating LCN2 can predict the extent of BMD recovery after parathyroidectomy in PHPT remains unclear. Clinical data and preoperative serum samples obtained from 35 PHPT patients (women n=30) who underwent parathyroidectomy at Severance hospital, Seoul, Korea between 2016 and 2019 were analyzed. Among 35 patients, 25 patients underwent BMD before surgery and two years after surgery. LCN2 was measured using enzyme-linked immunosorbent assay kit (DLCN20, R&D Systems, USA). Primary outcome was two-year lumbar spine BMD change (%). Mean age of study subjects was 57±13 years. Calcium and parathyroid hormone (PTH) levels restored to normal range after parathyroidectomy in all subjects (calcium [mean 8.7±0.4mg/dL]; PTH [median 33.3], 25.9 to 47.4 pg/mL). Baseline BMD of lumbar spine(LS), femoral neck(FN), and total hip(TH) were 0.776±0.177 g/cm2, 0.578±0.138 g/cm2, and 0.695±0.150 g/cm2, respectively. At 1 year after parathyroidectomy, BMD increased up to 5.5%, 6.1%, and 4.5% at LS, FN, and TH, respectively. At 2 years after parathyroidectomy, BMD increased up to 8.6%, 7.6%, and 7.2% at LS, FN, and TH, respectively. Log-transformed LCN2 at baseline showed positive correlation with LS BMD changes (%) after 2 years (β Coefficient = 3.46, 95% CI = 0.83 to 6.10, p-value = 0.012). In multiple linear regression model, one log-unit increment in LCN2 was associated with 4.7 percent point increase in LSBMD at two years after parathyroidectomy (adjusted β=4.72, 95% CI = 1.62 to 7.82, p-value = 0.005) after adjustment of PTH, creatinine level, and body mass index. This result remained robust for 3 year change in LSBMD (in subgroup, n=14; adjusted β=4.70, 95% CI = 0.9 to 8.5, p-value = 0.021). In conclusion, preoperative high circulating LCN2 level was associated with more LSBMD gain after parathyroidectomy in patients with PHPT.
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

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

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, > 2 and <5 years and ≥5 years) and according to the percentage of weight loss (10–20%, >20% and <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

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 <30 ng/ml, 18 patients (62.0%) had 25OHD levels <20 ng/ml and 10 patients (34.5%) had severe vitamin D deficiency (<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 (<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 <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 (<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 (<20 ng/ml), sex, BMI, age (<70 years) and ARDS as independent variables. Notably, hypovitaminosis D (β=0.49, P<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

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 <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

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

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

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 <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

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 >200 and PAC >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

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.
Why Should We Measure Low-Density Lipoprotein Cholesterol Directly? Comparison of Low-Density Lipoprotein Cholesterol Assessment by Friedewald Estimation, and Direct Measurement
Authors: Cohen Hofit
Published: May 2021

Intorduction: Plasma levels of low-density lipoprotein cholesterol (LDL-C) are an important biomarker for coronary artery disease. In clinical and research settings worldwide, levels LDL-C are often not measured and are estimated using the Friedewald equation (total cholesterol - HDL cholesterol - triglycerides)/5). Bias of either over or underestimation of LDL-C can be corrected by direct measurement of LDL-C. We assessed the precision of the Friedewald equation in a heterogonous patients population within a wide range of lipid levels. Methods: A sample of consecutive fasting lipid profiles was obtained from ambulatory and hospitalized patients at the Chaim Sheba Medical Center, Tel-Hashomer. LDL-C concentrations were directly measured (dir LDL-C) (Olympus, Ireland) and correspondingly calculated at by the Friedewald equation (calc LDL-C). Results: 32,245 samples were analyzed. In 93% of the samples, underestimation of plasma levels of LDL-C was observed using the Friedewald equation. In 11,054 patients (34.3%), the difference between dir LDL and calc LDL were over 10mg/dl. In 7,693 patients (23.8%), the difference between dir LDL and calc LDL were over 20mg/dl. The difference between dir LDL and calc LDL correlated with plasma TG levels, including TG levels within the normal range. The difference between cal LDL and dir LDL levels is inversely correlated to cholesterol plasma levels. Conclusions: Direct measurement of LDL-C is more precise than Friedewald’s formula and overcomes the inaccurateness, due to elevated TG levels or relatively low LDL-C levels, in the setting of a heterogeneous Israeli population. In the era of extremely low LDL-C treatment goals, our findings require consideration due to their clinical importance and direct measurement of plasma LDL-C should be implemented as underestimation of LDL levels may lead to inappropriate therapeutic decisions.