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Correction: Vitamin D status and supplementation before and after Bariatric Surgery: Recommendations based on a systematic review and meta‑analysis.
Giustina, A, di Filippo, L, Facciorusso, A, Adler, RA, Binkley, N, Bollerslev, J, Bouillon, R, Casanueva, FF, Cavestro, GM, Chakhtoura, M, et al
Reviews in endocrine & metabolic disorders. 2024;(2):447-448
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Vitamin D status and supplementation before and after Bariatric Surgery: Recommendations based on a systematic review and meta-analysis.
Giustina, A, di Filippo, L, Facciorusso, A, Adler, RA, Binkley, N, Bollerslev, J, Bouillon, R, Casanueva, FF, Cavestro, GM, Chakhtoura, M, et al
Reviews in endocrine & metabolic disorders. 2023;(6):1011-1029
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Abstract
Bariatric surgery is associated with a postoperative reduction of 25(OH) vitamin D levels (25(OH)D) and with skeletal complications. Currently, guidelines for 25(OH)D assessment and vitamin D supplementation in bariatric patients, pre- and post-surgery, are still lacking. The aim of this work is to analyse systematically the published experience on 25(OH)D status and vitamin D supplementation, pre- and post-surgery, and to propose, on this basis, recommendations for management. Preoperatively, 18 studies including 2,869 patients were evaluated. Prevalence of vitamin D insufficiency as defined by 25(OH)D < 30 ng/mL (75 nmol/L) was 85%, whereas when defined by 25(OH)D < 20 ng/mL (50 nmol/L) was 57%. The median preoperative 25(OH)D level was 19.75 ng/mL. After surgery, 39 studies including 5,296 patients were analysed and among those undergoing either malabsorptive or restrictive procedures, a lower rate of vitamin D insufficiency and higher 25(OH)D levels postoperatively were observed in patients treated with high-dose oral vitamin D supplementation, defined as ≥ 2,000 IU/daily (mostly D3-formulation), compared with low-doses (< 2,000 IU/daily). Our recommendations based on this systematic review and meta-analysis should help clinical practice in the assessment and management of vitamin D status before and after bariatric surgery. Assessment of vitamin D should be performed pre- and postoperatively in all patients undergoing bariatric surgery. Regardless of the type of procedure, high-dose supplementation is recommended in patients after bariatric surgery.
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A suggested protocol for the endocrine postoperative management of patients undergoing pituitary surgery.
Zarzour, F, Hage, M, Sanson, MR, Baussart, B, Chakhtoura, M
Annales d'endocrinologie. 2023;(4):413-423
Abstract
PURPOSE Endocrine disorders are the most frequent postoperative complications in patients undergoing pituitary surgery. Given the absence of recent guidelines on the postoperative care following pituitary surgery, this article summarizes the available evidence on the topic. METHOD We conducted a systematic search of PubMed up to 2021 and updated the search in December 2022. We retrieved 119 articles and included 53 full-text papers. RESULTS The early postoperative care consists of the assessment for cortisol deficiency and diabetes insipidus (DI). Experts suggest that all patients should receive a glucocorticoid (GC) stress dose followed by a rapid taper. The decision for GC replacement after discharge depends on the morning plasma cortisol level on day 3 after surgery. Experts suggest that patients with a morning plasma cortisol<10 mcg/dL should receive GC replacement at discharge, and those with 10-18 mcg/dL a morning dose only, with formal assessment of the hypothalamic-pituitary-adrenal axis at week 6 postoperatively. When the cortisol level is>18 mcg/dL, the patient can be discharged safely without GC, as suggested by observational studies. Postoperative care also includes a close monitoring of water balance. If DI develops, desmopressin is used only in case of uncomfortable polyuria or hypernatremia. The assessment of other hormones is indicated at 3 months postoperatively and beyond. CONCLUSION The evaluation and treatment of patients following pituitary surgery are based on expert opinion and a few observational studies. Further research is needed to provide additional evidence on the most appropriate approach.
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The Genetic Architecture of Vitamin D Deficiency among an Elderly Lebanese Middle Eastern Population: An Exome-Wide Association Study.
Hendi, NN, Chakhtoura, M, Al-Sarraj, Y, Basha, DS, Albagha, O, Fuleihan, GE, Nemer, G
Nutrients. 2023;(14)
Abstract
The Middle East region experiences a high prevalence of vitamin D deficiency, yet most genetic studies on vitamin D have focused on European populations. Furthermore, there is a lack of research on the genomic risk factors affecting elderly people, who are more susceptible to health burdens. We investigated the genetic determinants of 25-hydroxyvitamin D concentrations in elderly Lebanese individuals (n = 199) through a whole-exome-based genome-wide association study. Novel genomic loci displaying suggestive evidence of association with 25-hydroxyvitamin D levels were identified in our study, including rs141064014 in the MGAM (p-value of 4.40 × 10-6) and rs7036592 in PHF2 (p-value of 8.43 × 10-6). A meta-analysis of the Lebanese data and the largest European genome-wide association study confirmed consistency replication of numerous variants, including rs2725405 in SLC38A10 (p-value of 3.73 × 10-8). Although the polygenic risk score model derived from European populations exhibited lower performance than European estimations, it still effectively predicted vitamin D deficiency among our cohort. Our discoveries offer novel perspectives on the genetic mechanisms underlying vitamin D deficiency among elderly Middle Eastern populations, facilitating the development of personalized approaches for more effective management of vitamin D deficiency. Additionally, we demonstrated that whole-exome-based genome-wide association study is an effective method for identifying genetic components associated with phenotypes.
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Classical and Nonclassical Manifestations of Primary Hyperparathyroidism.
El-Hajj Fuleihan, G, Chakhtoura, M, Cipriani, C, Eastell, R, Karonova, T, Liu, JM, Minisola, S, Mithal, A, Moreira, CA, Peacock, M, et al
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2022;(11):2330-2350
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Abstract
This narrative review summarizes data on classical and nonclassical manifestations of primary hyperparathyroidism (PHPT). It is based on a rigorous literature search, inclusive of a Medline search for systematic reviews from 1940 to December 2020, coupled with a targeted search for original publications, covering four databases, from January 2013-December 2020, and relevant articles from authors' libraries. We present the most recent information, identify knowledge gaps, and suggest a research agenda. The shift in the presentation of PHPT from a predominantly symptomatic to an asymptomatic disease, with its varied manifestations, has presented several challenges. Subclinical nephrolithiasis and vertebral fractures are common in patients with asymptomatic disease. The natural history of asymptomatic PHPT with no end organ damage at diagnosis is unclear. Some observational and cross-sectional studies continue to show associations between PHPT and cardiovascular and neuropsychological abnormalities, among the different disease phenotypes. Their causal relationship is uncertain. Limited new data are available on the natural history of skeletal, renal, cardiovascular, neuropsychological, and neuromuscular manifestations and quality of life. Normocalcemic PHPT (NPHPT) is often diagnosed without the fulfillment of rigorous criteria. Randomized clinical trials have not demonstrated a consistent long-term benefit of parathyroidectomy (PTX) versus observation on nonclassical manifestations. We propose further refining the definition of asymptomatic disease, into two phenotypes: one without and one with evidence of target organ involvement, upon the standard evaluation detailed in our recommendations. Each of these phenotypes can present with or without non-classical manifestations. We propose multiple albumin-adjusted serum calcium determinations (albumin-adjusted and ionized) and exclusion of all secondary causes of high parathyroid hormone (PTH) when establishing the diagnosis of NPHPT. Refining the definition of asymptomatic disease into the phenotypes proposed will afford insights into their natural history and response to interventions. This would also pave the way for the development of evidence-based guidance and recommendations. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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Long Term Weight Loss Diets and Obesity Indices: Results of a Network Meta-Analysis.
Jabbour, J, Rihawi, Y, Khamis, AM, Ghamlouche, L, Tabban, B, Safadi, G, Hammad, N, Hadla, R, Zeidan, M, Andari, D, et al
Frontiers in nutrition. 2022;9:821096
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Obesity is associated with a decreased lifetime expectancy of 5–20 years, depending on the severity and the presence of comorbidities. Diet therapy remains one of the cornerstones of the multi-disciplinary approach to weight management. The aim of this study was to evaluate the association of long-term dietary interventions, categorised using the Acceptable Macronutrient Distribution Ranges, with changes in weight parameters. This study is a systematic review and network meta-analysis of fifty studies. Results indicate that compared with the usual diet, all dietary interventions allow a sustained modest weight loss during the follow-up of 12 months and beyond. Diets did not differ among each other, with the exception of the high-fat low-carbohydrate diet that was slightly better than the low-carbohydrate, low-fat, and moderate macronutrients diet, with a larger weight loss (of 0.8 kg) and body mass index loss (0.4 kg/m2 ). Authors conclude that even though their findings apply to the general population of patients with overweight/obesity, the long-term impact of dietary approaches on patients with chronic diseases should be further investigated.
Abstract
Background: Scientists have been investigating efficient interventions to prevent and manage obesity. This network meta-analysis (NMA) compared the effect of different diets [moderate macronutrients (MMs), low fat/high carbohydrate (LFHC), high fat/low carbohydrate (HFLC), and usual diet (UD)] on weight, body mass index (BMI), and waist circumference (WC) changes at ≥12 months. Methods: We searched Medline, Embase, PubMed databases, and the Cochrane Library. We systematically assessed randomized controlled trials (RCTs) evaluating dietary interventions on adults (mean BMI ≥ 25 kg/m2) receiving active dietary counseling for ≥12 months. We pooled the data using a random-effect NMA. We assessed the quality of the included RCTs using the Cochrane risk of bias (ROB) tool. Results: We included 36 trials, 14 of which compared HFLC with MM diets. Compared with UD, all diets were associated with a significant weight loss (WL) at ≥12 months, HFLC [mean difference in kg (95% CI): -5.5 (-7.6; -3.4)], LFHC [-5.0 (-7.1; -2.9)] and MM [-4.7 (-6.8; -2.7)]. HFLC, compared with MM diet, was associated with a slightly higher WL (of -0.77 kg) and drop in BMI (of -0.36 kg/m2), while no significant difference was detected in other dietary comparisons. WC was lower with all diets compared to UD, with no significant difference across specific diets. There was no significant interaction of the results with the pre-specified sub-groups. The ROB was moderate to high, mostly related to unclear allocation concealment, high dropout rate and unclear or lack of blinding of participants, providers, and outcome assessors. Conclusion: Dietary interventions extending over ≥12 months are superior to UD in inducing weight, BMI and WC loss. HFLC might be associated with a slightly higher WL compared with MM diets. Systematic Trial Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=103116, PROSPERO (CRD42018103116).
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Effect of antiresorptive therapy on aromatase inhibitor induced bone loss in postmenopausal women with early-stage breast cancer: A systematic review and meta-analysis of randomized controlled trials.
Bassatne, A, Bou Khalil, A, Chakhtoura, M, Arabi, A, Van Poznak, C, El-Hajj Fuleihan, G
Metabolism: clinical and experimental. 2022;:154962
Abstract
BACKGROUND Aromatase inhibitors (AIs) are routinely used to treat postmenopausal women with early-stage breast cancer. Although AIs improve breast cancer outcomes, they increase the risk of osteoporosis and fractures. This systematic review and meta-analysis assesses the effect of antiresorptive drugs on AI induced bone loss in postmenopausal women with non-metastatic breast cancer. METHODS We searched four databases until November 4th 2020. We included Randomized controlled trials (RCTs) of antiresorptive drugs in postmenopausal women with breast cancer treated with AI. Two authors screened studies, extracted data and assessed the risk of bias independently and in duplicate. RESULTS We identified 14 RCTs: 7 on zoledronic acid, 6 on oral bisphosphonates and 1 on denosumab. The mean difference in bone mineral density (BMD) was 5% at the lumbar spine and 4% at the total hip, at 12 months, favoring zoledronic acid compared to control. The certainty of the evidence was low for lumbar spine and moderate for total hip BMD. Similarly, the mean difference was 3% at the lumbar spine and 2% at the total hip, favoring oral bisphosphonates with moderate certainty. The mean difference was 6% at the lumbar spine, and 4% at the total hip BMD favoring denosumab compared to placebo. In addition, zoledronic acid resulted in a mean difference in bone turnover marker levels of -35-41%, and the relarive risk for morphometric vertebral fractures was 0.7 [0.3-1.4], compared to control. Denosumab reduced fracture incidence by 50% compared to placebo. CONCLUSION Evidence suggests a protective effect of antiresorptive drugs on BMD and bone turnover markers in postmenopausal women with non-metastatic breast cancer on AI. However, data on fracture risk reduction remains unclear.
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Fracture risk following bariatric surgery: a systematic review and meta-analysis.
Saad, RK, Ghezzawi, M, Habli, D, Alami, RS, Chakhtoura, M
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2022;(3):511-526
Abstract
Bariatric surgery may negatively impact bone health. We aimed to compare fracture risk following bariatric surgery by type (malabsorptive, restrictive), or to non-surgical weight loss, or to controls with obesity. We systematically searched four databases from inception until October 2020. We included observational and interventional studies on adults. We screened articles and abstracted data in duplicate and independently and assessed the risk of bias. We conducted random-effects model meta-analyses (Review Manager v5.3), to calculate the relative risk of any or site-specific fracture (CRD42019128536). We identified four trials of unclear-to-high risk of bias and 15 observational studies of fair-to-good quality. Data on fracture risk following bariatric surgery compared to medical weight loss is scarce and limited by the small number of participants. In observational studies, at a mean/median post-operative follow-up > 2 years, the relative risk of any fracture was 45% (p < 0.001) and 61% (p = 0.04) higher following malabsorptive procedures compared to obese controls and restrictive procedures, respectively, with moderate to high heterogeneity. Site-specific relative fracture risk (hip and wrist) was one- to two-folds higher post malabsorptive procedures compared to obese controls or restrictive procedures. The risks of any and of site-specific fracture were not increased following restrictive procedures compared to obese controls. Fracture risk seems to increase following malabsorptive bariatric surgeries, at a mean/median follow-up > 2 years. The risk is not increased with restrictive surgeries. The available evidence has several limitations. A prospective and rigorous long-term follow-up of patients following bariatric surgery is needed for a better assessment of their fracture risk with aging.
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Vitamin D Supplementation and Fractures in Adults: A Systematic Umbrella Review of Meta-Analyses of Controlled Trials.
Chakhtoura, M, Bacha, DS, Gharios, C, Ajjour, S, Assaad, M, Jabbour, Y, Kahale, F, Bassatne, A, Antoun, S, Akl, EA, et al
The Journal of clinical endocrinology and metabolism. 2022;(3):882-898
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Abstract
CONTEXT The growing number of systematic reviews/meta-analyses (SR/MAs) on vitamin D (± calcium) for fracture prevention has led to contradictory guidelines. OBJECTIVE This umbrella review aims to assess the quality and explore the reasons for the discrepancy of SR/MAs of trials on vitamin D supplementation for fracture risk reduction in adults. METHODS We searched 4 databases (2010-2020), Epistemonikos, and references of included SRs/MAs, and we contacted experts in the field. We used A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR-2) for quality assessment. We compared results and investigated reasons for discordance using matrices and subgroup analyses (PROSPERO registration: CRD42019129540). We included 13 SR/MAs on vitamin D and calcium (Ca/D) and 19 SR/MAs on vitamin D alone, compared to placebo/control. RESULTS Only 2 from 10 SRs/MAs on Ca/D were of moderate quality. Ca/D reduced the risk of hip fractures in 8 of 12 SRs/MAs (relative risk [RR] 0.61-0.84), and any fractures in 7 of 11 SR/MAs (RR 0.74-0.95). No fracture risk reduction was noted in SRs/MAs exclusively evaluating community-dwelling individuals or in those on vitamin D alone compared to placebo/control. Discordance in results between SRs/MAs stems from inclusion of different trials, related to search periods and eligibility criteria, and varying methodology (using intention to treat, per-protocol, or complete case analysis from individual trials). CONCLUSION Ca/D reduces the risk of hip and any fractures, possibly driven by findings from institutionalized individuals. Individual participant data meta-analyses of patients on Ca/D with sufficient follow-up periods, and subgroup analyses, would unravel determinants for a beneficial response to supplementation.
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Abdominal Visceral Adipose Tissue and All-Cause Mortality: A Systematic Review.
Saad, RK, Ghezzawi, M, Horanieh, R, Khamis, AM, Saunders, KH, Batsis, JA, Chakhtoura, M
Frontiers in endocrinology. 2022;:922931
Abstract
INTRODUCTION Increased abdominal visceral adipose tissue (VAT) implies an adverse cardio-metabolic profile. We examined the association of abdominal VAT parameters and all-cause mortality risk. METHODS We systematically searched four databases. We performed citations/articles screening, data abstraction, and quality assessment in duplicate and independently (CRD42020205021). RESULTS We included 12 cohorts, the majority used computed tomography to assess abdominal VAT area. Six cohorts with a mean age ≤ 65 years, examining all-cause mortality risk per increment in VAT area (cm2) or volume (cm3), showed a 11-98% relative risk increase with higher VAT parameters. However, the association lost significance after adjusting for glycemic indices, body mass index, or other fat parameters. In 4 cohorts with a mean age >65 years, the findings on mortality were inconsistent. Conversely, in two cohorts (mean age 73-77 years), a higher VAT density, was inversely proportional to VAT area, and implied a higher mortality risk. CONCLUSION A high abdominal VAT area seems to be associated with increased all-cause mortality in individuals ≤ 65 years, possibly mediated by metabolic complications, and not through an independent effect. This relationship is weaker and may reverse in older individuals, most likely secondary to confounding bias and reverse causality. An individual participant data meta-analysis is needed to confirm our findings, and to define an abdominal VAT area cutoff implying increased mortality risk. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=205021, identifier CRD42020205021.