Triglyceride-Glucose Index, HOMA Index and metabolic syndrome in a sample of adult men.

BACKGROUND: Metabolic syndrome (MetS) and its components are directly associated with cardiovascular risk. Insulin resistance (IR) is the most common pathophysiological feature of MetS. A novel index, the triglyceride-glucose index (TyG), is considered a surrogate marker of IR. Hence, we estimated the ability of TyG to predict the risk to develop MetS over a follow-up period of 8 years. In addition, we compared the predictive role of TyG and that of the HOmeostatis Model Assessment (HOMA) of IR index (a widely used tool to evaluate IR). METHODS: The analysis included 440 adult men (The Olivetti Heart Study) without MetS at baseline. The optimal cut-off point of the association of continuous TyG or HOMA-IR with MetS was identified by ROC analysis. RESULTS: During the follow-up period, 21.6% of participants developed MetS. Baseline TyG and HOMA-IR were both significantly greater in those who developed MetS than in those who did not. These results were confirmed upon adjustment for the main confounders. After stratification by the optimal cut-off point, TyG >4.78 was a significant predictor of MetS, also after adjustment for main confounders. Likewise, HOMA-IR >2.14 was associated with the risk of MetS development in multivariate models. CONCLUSIONS: The results of this prospective study indicate a significant predictive role of TyG on the risk of MetS, independently of the main confounders. They suggest that TyG may serve as a low-cost and simple non-invasive marker for cardio-metabolic risk stratification, with respect to more complex and expensive assays of IR requiring the insulin measurement.

Adherence to Mediterranean Diet, Dietary Salt Intake, and Susceptibility to Nephrolithiasis: A Case-Control Study.

Unhealthy dietary habits play a key role in the pathogenesis of nephrolithiasis (NL). The aims of this case-control study were to evaluate (i) the adherence to the Mediterranean Diet (MD) and the dietary salt intake in stone-forming patients (SF), (ii) the relationship occurring between MD adherence, salt intake and NL-related metabolic risk factors in SF, and (iii) the impact of combined high MD adherence and low salt intake on NL susceptibility. From 1 January 2018 to 31 December 2019, we recruited all SF consecutively referred to the Extracorporeal Shock Wave Lithotripsy (ESWL) center of Federico II University, and at least two control subjects without a personal history of NL, age-, sex-, and body mass index-matched to SF (NSF). All study participants were interviewed using the validated MEDI-LITE and MINISAL questionnaires. In an SF subgroup, the NL-related metabolic risk factors were also evaluated. SF showed a lower MD adherence and a higher salt intake compared with NSF. The NL susceptibility decreased by 36% [OR: 0.64 (0.59-0.70); p < 0.01] for each point of increase in MEDI-LITE score, while it increased by 13% [OR: 1.13 (1.03-1.25); p = 0.01] for each point of increase in MINISAL score. The SF prevalence was higher among subjects showing combined low MD adherence and high salt intake. In SF, the MEDI-LITE score directly correlated with 24 h-citraturia, whereas the MINISAL score directly correlated with urinary sodium and uric acid excretion. In conclusion, high MD adherence and low salt intake are associated with a reduced NL susceptibility, both separately and in combination.

Integrated Management of an Adult Patient with Mucopolysaccharidosis type IVA: A Case Report with a Six-Year Follow-up.

Mucopolysaccharidosis type IVA (MPS-IVA) is a rare lysosomal storage disease caused by N-acetylglucosamine-6-sulfate-sulfatase enzyme deficiency. MPS-IVA patients show severe extra-skeletal and skeletal manifestations, featured by bone pain and deformities, frailty fractures and early onset osteoporosis. The enzyme replacement therapy (ERT) with elosulfase-α stabilizes the MPS-IVA extra-skeletal manifestations but does not significantly improve MPS-IVA skeletal manifestations. We administered an integrated therapy to an MPS-IVA 41-year-old male patient, composed of zoledronic acid, cholecalciferol and a normocalcemic (calcium intake ≥1 g/day), hyposodic (sodium intake ≤5 g/day), and normocaloric diet (bone-diet), other than ERT. During the six-year follow-up, the patient did not develop any adverse events, obtaining an improvement of bone mineral density and quality of life. Given our results, we propose this integrated treatment (i.e. ERT, zoledronic acid, cholecalciferol, and bone diet) in the management of MPS-IVA adult patients. LEARNING POINTS: Mucopolysaccharidosis type IVA (MPS-IVA) is a genetic, rare, and degenerative spondylo-epiphyso-metaphyseal dysplasia characterized by extra-skeletal and skeletal manifestations. The latter impacts on MPS-IVA patient daily activities, and enzyme replacement therapy has a poor efficacy in improving skeletal involvement.The proposed integrated management with enzyme replacement therapy, zoledronic acid, cholecalciferol and bone diet improve both bone mineral density and the prognosis quoad valetudinem of our MPS-IVA patient.

Calcium-phosphate homeostasis and insulin resistance in men.

BACKGROUND AND AIMS: Data on P homeostasis in insulin resistance (IR) are still conflicting. We investigated calcium-phosphate homeostasis parameters in men with/without IR. METHODS AND RESULTS: 177 volunteers (aged 61.62 ± 12.11), whose body mass index (BMI) was 29.97 ± 6.35, were studied. On fasting blood and spot urine samples, we measured serum creatinine, sodium (sNa), potassium (sK), chloride (sCl), calcium (sCa), phosphate (sP), alkaline phosphatase total activity (ALP), glucose, insulin, parathyroid hormone (PTH), 25-hydroxy-vitamin D [25(OH)D], and urinary electrolytes corrected for creatinine (uNa/Cr, uK/Cr, uCl/Cr, uCa/Cr, and uP/Cr). Through the QUICKI index, we separated subjects with (IR+, n = 68) or without (IR-, n = 109) IR, and their parameters were compared. Associations were assessed by age-adjusted partial correlation, whose coefficients were compared by Fisher's transform. IR + had higher sP (3.54 ± 0.65 vs. 3.35 ± 0.47, p = 0.044) and lower uCa/Cr levels (0.073 ± 0.056 vs. 0.095 ± 0.072, p = 0.047) than IR-. BMI correlated with sP (r = 0.21, p < 0.05) and PTH (r = 0.29, p < 0.01). QUICKI negatively correlated with sCa (r = -0.22, p < 0.05) and positively with uCa/Cr (r = 0.21, p < 0.05), in turn correlating with uNa/Cr (r = 0.45, p < 0.001). In both groups, uCa/Cr correlated with eGFR and uNa/Cr (p < 0.05 to p < 0.001). In IR + only, sP correlated with BMI, PTH with insulin, and uP/Cr (p < 0.05 for all). IR+ and IR-coefficients differed (p < 0.05 to p < 0.001) for the correlation of sP with BMI and of PTH with insulin and uP/Cr. CONCLUSION: The higher sP and lower uCa/Cr levels found in men with IR + suggest that IR could modulate calcium-phosphate homeostasis, likely by affecting their renal handling.

Clinical Characteristics of Malignant Phosphaturic Mesenchymal Tumor Causing Tumor-Induced Osteomalacia.

CONTEXT: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome usually caused by oversecretion of fibroblast growth factor 23 (FGF23) from a phosphaturic mesenchymal tumor (PMT). PMTs are usually benign neoplasms but some of them show malignant characteristics. OBJECTIVE: The aim of this study was to compare the clinical characteristics of benign and malignant PMTs inducing TIO. METHODS: On March 31, 2023, we performed a systematic review of individual patient data analysis in Medline, Google Scholar, Google book, and Cochrane Library using the terms "tumor induced osteomalacia," "oncogenic osteomalacia," "hypophosphatemia," with no language restrictions and according to Preferred Reporting Items for Systematic reviews and Meta-Analyses criteria. RESULTS: Overall, we collected data from 837 patients with TIO in which the diagnosis of benign and malignant PMT was specified. Of them, 89 were affected by malignant PMT and 748 by benign PMT. Patients with malignant PMTs were younger and presented bone pain, functional impairment, and bone deformities more frequently. Malignant PMTs showed higher values of intact FGF23 and a higher mortality rate. CONCLUSION: The study results identify the clinical characteristics of patients with malignant TIO, permitting the early identification of patients with PMT at increased risk of malignancy. This may significantly improve the diagnostic approach to disease. Further experimental studies are mandatory to clarify the role of FGF23 in the pathogenesis of malignancy in PMTs.

Venous thromboembolism and major bleeding in severe and critical COVID-19 hospitalized patients.

Venous thromboembolism (VTE) and major bleeding (MB) are life-threatening complications described in COVID-19 hospitalized patients and they can be considered as two sides of the same coin. This retrospective study aims to evaluate the risk factors for VTE and MB in COVID-19 patients admitted to two Italian hospitals. The medical records of all COVID-19 patients (males 139; 62.3%, mean age 67.2±13.6 years, body weight 88.2±20.6 kg) hospitalized from March 11th to July 31st, 2020 to the Federico II University Hospital and to Sea Hospital, Naples, Italy, were analyzed. The COVID-19 patients were classified into four groups: COVID-19 patients developing VTE and/or MB, COVID-19 patients developing only VTE, COVID-19 patients developing only MB, and COVID-19 patients not developing neither VTE nor MB. During the hospitalization, 53 COVID-19 patients (24.7%; males 40; 75.5%, mean age 67.2±13.6 years, weight 88.2±20.6 kg) developed VTE, 33 COVID-19 patients (15.3 %; males 17; 51.5, mean age 67.3±14.9 years, weight 74.1±14.3 kg) developed MB, and 129 COVID-19 patients not developed neither TVP nor MB. No parameters to identify severe COVID-19 complicated by VTE and/or MB were found. However, some clinical and biochemical parameters can be evaluated to predict the risk of MB in order to modify the treatment and take prompt action to reduce mortality.

Low Potassium Intake: A Common Risk Factor for Nephrolithiasis in Patients with High Blood Pressure.

Hypertension (Htn) is a crucial cause of cardio-vascular and chronic kidney disease. Moreover, it is an independent risk factor for nephrolithiasis (NL). A diet rich in vegetables and fruits is indicated for both Htn and NL prevention, and the 24-h urinary potassium excretion can be used as a warning light for adherence. The aim of this study is to demonstrate the association between urinary potassium excretion and recurrent nephrolithiasis among patients affected by Htn. We have analyzed medical records of 119 patients affected by Htn and NL (SF-Hs) referring to Bone and Mineral Metabolism laboratory and 119 patients affected by Htn but without NL (nSF-Hs) referring to Hypertension and Organ Damage Hypertension related laboratory, both in Federico II University of Naples. The potassium 24-h urinary levels in SF-Hs were significantly lower compared to nSF-Hs. This difference was confirmed by the multivariable linear regression analysis in the unadjusted model and adjusted model for age, gender, metabolic syndrome, and body mass index. In conclusion, a higher potassium urinary excretion in 24-h is a protective factor against NL in patients affected by Htn and dietary interventions can be considered for kidney protection.

Drug treatment strategies for paget's disease: relieving pain and preventing progression.

INTRODUCTION: Paget's disease of bone (PDB) is a focal bone disorder caused by a marked dysregulation of osteoblasts and osteoclasts in basic multicellular units, leading to abnormal and disorganized deposition of collagen fibers (the so-called 'woven bone'). Therefore, pagetic bones are increased in size, and at increased risk for bone pain, deformities, fractures, osteoarthritis, and, more rarely, neoplastic degeneration. AREAS COVERED: In this review, we revise the available information concerning the pharmacological treatment of PDB. EXPERT OPINION: PDB progresses slowly within the affected skeletal sites and, if untreated, often leads to bone overgrowth, with bone pain, deformity, and a likely increased risk of complications. Thus, the primary goal of treatment is the restoration of a normal bone turnover, in order to relieve bone pain or other symptoms and possibly prevent the complications. PDB long remained a poorly treatable disorder until the discovery of antiresorptive agents such as calcitonin first and bisphosphonates (BPs) later. With the recent development of potent intravenous BPs like zoledronate, allowing a better control of disease activity over the long term with a single infusion, has contributed to a marked improvement of the clinical management of this invalidating disorder.

Effect of Potassium Supplementation on Endothelial Function: A Systematic Review and Meta-Analysis of Intervention Studies.

(1) Background: Endothelial dysfunction is an early predictor of cardiovascular diseases. Although a large body of evidence shows an inverse association between potassium intake and cardiovascular risk, the studies on endothelial function provided contrasting results. Thus, we carried out a systematic review and a meta-analysis of the available intervention studies of the potassium supplementation on endothelial function. (2) Methods: A systematic search of the online databases available (up to December 2022) was conducted including the intervention trials that reported flow-mediated dilation (FMD) changes-a non-invasive method of assessing endothelial function-after two different potassium intake regimens. For each study, the mean difference (MD) and 95% confidence intervals were pooled using a random effect model. (3) Results: Five studies met the pre-defined inclusion criteria and provided eight cohorts with 332 participants. In the pooled analysis, potassium supplementation was associated with a significant increase in FMD (MD: 0.74%), with a higher effect for a urinary potassium excretion higher than 90 mmol/day. There was a moderate heterogeneity among studies (I2 = 59%), explained by the different amount of potassium supplementation. (4) Conclusions: The results of our meta-analysis indicate that dietary potassium supplement improves endothelial function. This effect is directly associated with the amount of potassium supplement. The findings support the campaigns in favour of an increase in dietary potassium intake to reduce cardiovascular risk.

Reply to Wimalawansa, S.J. Comment on "Bertoldo et al. Definition, Assessment, and Management of Vitamin D Inadequacy: Suggestions, Recommendations, and Warnings from the Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS). Nutrients 2022, 14, 4148".

With regard to Dr. Wimalawansa's comment [...].

25-Hydroxy-Vitamin D and Risk of Recurrent Stroke: A Dose Response Meta-Analysis.

Stroke recurrence significantly improves the prognosis quoad vitam et valetudinem of patients with a first ischemic or haemorrhagic stroke. Other than in bone and skeletal metabolism, vitamin D is involved in the pathogenesis of cardiovascular disorders. This meta-analysis was performed to evaluate the relationship between 25OH-vitamin D [25(OH)D] levels at the first stroke and the stroke recurrence. To 31 July 2022, four prospective studies were identified. The potential non-linear relationship was evaluated by modelling 25(OH)D, using restricted cubic splines of 25(OH)D distribution. The pooled estimated risk (and 95% CI) of the recurrence of stroke, comparing the highest and the lowest levels, was assessed using a random-effect model. A non-linear association was found by dose-response analysis. This study found that 25(OH)D levels at the first stroke ≥9.3 ng/mL were associated with a lower risk of stroke recurrence, compared with 25(OH)D levels ≤8.5 ng/mL. In the pooled analysis, higher 25(OH)D levels at the first stroke significantly reduce the risk of stroke recurrence, with a significant heterogeneity among studies. In conclusion, 25(OH)D levels ≤8.5 ng/mL at the first stroke are significantly associated with a higher risk of recurrent stroke.

Hypertension and mortality in SARS-COV-2 infection: A meta-analysis of observational studies after 2 years of pandemic.

BACKGROUND: The worldwide pandemic SARS-CoV-2 infection is associated with clinical course including a very broad spectrum of clinical manifestations, including death. Several studies and meta-analyses have evaluated the role of hypertension on prognosis, but with important limitations and conflicting results. Therefore, we decided to perform a new meta-analysis of the observational studies that explored the relationship between pre-existing hypertension and mortality risk in patients with SARS-CoV-2 infection, using more stringent inclusion criteria to overcome the limitations inherent previous meta-analyses. METHODS: A systematic search of the on-line databases available up to 31 March 2022 was conducted, including peer-reviewed original articles, involving the adult population, where the role of hypertension on mortality due to SARS-CoV-2 infection was determined by Cox-proportional hazard models. Pooled hazard ratio (HR) was calculated by a random effect model. Sensitivity, heterogeneity, publication bias, subgroup and meta-regression analyses were performed. RESULTS: Twenty-six studies (222,083 participants) met the pre-defined inclusion criteria. In the pooled analysis, pre-existing hypertension was significantly associated with mortality due to SARS-CoV-2 infection, both in unadjusted and adjusted models (HR: 1.55; 95% CI: 1.22 to 1.97). However, in separate analyses including results adjusted for crucial and strong predictors of mortality during SARS-CoV-2 infection (e.g. body weight), the association disappeared. CONCLUSIONS: The results of this meta-analysis indicate that pre-existing hypertension is not an independent predictor of mortality during SARS-CoV-2 infection. Further studies should nevertheless be carried out worldwide to evaluate this role, independent of, or in interaction with, other confounders that may affect the mortality risk.

Validation of the clinical consensus recommendations on the management of fracture risk in postmenopausal women with type 2 diabetes.

BACKGROUND AND AIMS: Bone fragility is recognized as a complication of type 2 diabetes (T2D). However, the fracture risk in T2D is underestimated using the classical assessment tools. An expert panel suggested the diagnostic approaches for the detection of T2D patients worthy of bone-active treatment. The aim of the study was to apply these algorithms to a cohort of T2D women to validate them in clinical practice. METHODS AND RESULTS: The presence of T2D-specific fracture risk factors (T2D ≥ 10 years, ≥1 T2D complications, insulin or thiazolidinedione use, poor glycaemic control) was assessed at baseline in 107 postmenopausal T2D women. In all patients at baseline and in 34 patients after a median follow-up of 60.2 months we retrospectively evaluated bone mineral density and clinical and morphometric vertebral fractures. No patient was treated with bone-active drug. Following the protocols, 34 (31.8%) and 73 (68.2%) patients would have been pharmacologically and conservatively treated, respectively. Among 49 patients without both clinical fractures and major T2D-related risk factors, who would have been, therefore, conservatively followed-up without vertebral fracture assessment, only one showed a prevalent vertebral fracture (sensitivity 90%, negative predictive value 98%). The two patients who experienced an incident fracture would have been pharmacologically treated at baseline. CONCLUSIONS: The clinical consensus recommendations showed a very good sensitivity in identifying T2D postmenopausal women at high fracture risk. Among those with treatment indication as many as 13% of patients experienced an incident fracture, and, conversely, among those without treatment indication no incident fractures were observed.

The role of the general practictioner in the management of urinary calculi.

BACKGROUND: The prevalence of kidney stones tends to increase worldwide due to dietary and climate changes. Disease management involves a high consumption of healthcare system resources which can be reduced with primary prevention measures and prophylaxis of recurrences. In this field, collaboration between general practitioners (GPs) and hospitals is crucial. METHODS: a panel composed of general practitioners and academic and hospital clinicians expert in the treatment of urinary stones met with the aim of identifying the activities that require the participation of the GP in the management process of the kidney stone patient. RESULTS: Collaboration between GP and hospital was found crucial in the treatment of renal colic and its infectious complications, expulsive treatment of ureteral stones, chemolysis of uric acid stones, long-term follow-up after active treatment of urinary stones, prevention of recurrence and primary prevention in the general population. CONCLUSIONS: The role of the GP is crucial in the management and prevention of urinary stones. Community hospitals which are normally led by GPs in liaison with consultants and other health professional can have a role in assisting multidisciplinary working as extended primary care.

Definition, Assessment, and Management of Vitamin D Inadequacy: Suggestions, Recommendations, and Warnings from the Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS).

In the recent years, both the prescriptions of serum 25(OH)D levels assay, and vitamin D supplementation are constantly increasing, as well as the costs to be incurred relating to these specific aspects. As in many other countries, the risk of vitamin D deficiency is particularly high in Italy, as recently confirmed by cohort studies in the general population as well as in patients with metabolic bone disorder. Results confirmed the North-South gradient of vitamin D levels described among European countries, despite the wide use of supplements. Although vitamin D supplementation is also recommended by the Italian Medicine Agency for patients at risk for fragility fracture or for initiating osteoporotic medication, the therapeutic gap for osteoporosis in Italy is very high. There is a consistent proportion of osteoporotic patients not receiving specific therapy for osteoporosis following a fragility fracture, with a poor adherence to the recommendations provided by national guidelines and position paper documents. The failure or inadequate supplementation with vitamin D in patients on antiresorptive or anabolic treatment for osteoporosis is thought to further amplify the problem and exposes patients to a high risk of re-fracture and mortality. Therefore, it is important that attention to its possible clinical consequences must be given. Thus, in light of new evidence from the literature, the SIOMMMS board felt the need to revise and update, by a GRADE/PICO system approach, its previous original recommendations about the definition, prevention, and treatment of vitamin D deficiency in adults, released in 2011. Several key points have been here addressed, such as the definition of the vitamin D status: normality values and optimal values; who are the subjects considered at risk of hypovitaminosis D; opportunity or not of performing the biochemical assessment of serum 25(OH)D levels in general population and in subjects at risk of hypovitaminosis D; the need or not to evaluate baseline serum 25(OH)D in candidate subjects for pharmacological treatment for osteoporosis; how and whether to supplement vitamin D subjects with hypovitaminosis D or candidates for pharmacological treatment with bone active agents, and the general population; how and whether to supplement vitamin D in chronic kidney disease and/or chronic liver diseases or under treatment with drugs interfering with hepatic metabolism; and finally, if vitamin D may have toxic effects in the subject in need of supplementation.

Update on the pathogenesis and genetics of Paget's disease of bone.

Studies over the past two decades have led to major advances in the pathogenesis of Paget's disease of bone (PDB) and particularly on the role of genetic factors. Germline mutations of different genes have been identified, as a possible cause of this disorder, and most of the underlying pathways are implicated in the regulation of osteoclast differentiation and function, whereas other are involved in cell autophagy mechanisms. In particular, about 30 different germline mutations of the Sequestosome 1 gene (SQSTM1) have been described in a significant proportion of familial and sporadic PDB cases. The majority of SQSTM1 mutations affect the ubiquitin-binding domain of the protein and are associated to a more severe clinical expression of the disease. Also, germline mutations in the ZNF687 and PFN1 genes have been associated to severe, early onset, polyostotic PDB with increased susceptibly to neoplastic degeneration, particularly giant cell tumor. Mutations in the VCP (Valosin Containing Protein) gene cause the autosomal dominant syndrome "Inclusion Body Myopathy, PDB, Fronto-temporal Dementia," characterized by pagetic manifestations, associated with myopathy, amyotrophic lateral sclerosis and fronto-temporal dementia. Moreover, germline mutations in the TNFRSF11A gene, which encodes for RANK, were associated with rare syndromes showing some histopathological, radiological, and clinical overlap with PDB and in two cases of early onset PDB-like disease. Likewise, genome wide association studies performed in unrelated PDB cases identified other potential predisposition genes and/or susceptibility loci. Thus, it is likely that polygenic factors are involved in the PDB pathogenesis in many individuals and that modifying genes may contribute in refining the clinical phenotype. Moreover, the contribution of somatic mutations of SQSTM1 gene and/or epigenetic mechanisms in the pathogenesis of skeletal pagetic abnormalities and eventually neoplastic degeneration, cannot be excluded. Indeed, clinical and experimental observations indicate that genetic susceptibility might not be a sufficient condition for the clinical development of PDB without the concomitant intervention of viral infection, in primis paramixoviruses, and/or other environmental factors (e.g., pesticides, heavy metals or tobacco exposure), at least in a subset of cases. This review summarizes the most important advances that have been made in the field of cellular and molecular biology PDB over the past decades.

Vitamin D Status, Cardiovascular Risk Profile, and miRNA-21 Levels in Hypertensive Patients: Results of the HYPODD Study.

The vitamin D and microRNA (miR) systems may play a role in the pathogenesis of cardiometabolic disorders, including hypertension. The HYPODD study was a double-blind placebo-controlled trial aiming to assess the effects of cholecalciferol treatment in patients with well-controlled hypertension and hypovitaminosis D (25OHD levels < 50 nmol/L). In addition to this clinical trial, we also evaluated the effects of cholecalciferol and calcitriol treatment on miR-21 expression in vivo and in vitro, respectively. Changes in the cardiovascular risk profiles were evaluated in HYPODD patients treated with cholecalciferol (C-cohort) or with placebo (P-cohort). The miR-21circulating levels were measured in four C-cohort patients and five P-cohort patients. In vitro, the miR-21 levels were measured in HEK-293 cells treated with calcitriol or with ethanol vehicle control. Cholecalciferol treatment increased 25OHD levels and reduced parathormone, total cholesterol, and low-density lipoprotein cholesterol levels in C-cohort patients, whereas no significant changes in these parameters were observed in P-cohort patients. The miR-21 circulating levels did not change in the C- or the P-cohort patients upon treatment. Calcitriol treatment did not affect miR-21 levels in HEK-293 cells. In conclusion, hypovitaminosis D correction ameliorated the cardiovascular risk profiles in hypertensive patients treated with cholecalciferol but did not influence the miR-21 expression.

Iodine Requirements in Pediatrics: From Fetal Life to Adolescence.

The aim of this mini-review is to present the current knowledge on iodine requirements in developmental age, from conception to adolescence. It is based on the analysis of updated national and international guidelines on iodine intake and the prevention of iodine deficiency. Health policy initiatives carried out in industrialized countries in previous decades have led to a dramatic improvement in nutritional iodine status in the general population. However, the prevention of iodine deficit continues to be a concern, especially for vulnerable categories, like adolescents and pregnant women.

Tumor-induced Osteomalacia: A Systematic Review and Individual Patient's Data Analysis.

CONTEXT: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome, usually caused by small, benign, and slow-growing phosphaturic mesenchymal tumors. Clinically, TIO is characterized by renal phosphate leak, causing hypophosphatemia and osteomalacia. This review was performed to assess the clinical characteristics of TIO patients described worldwide so far. EVIDENCE ACQUISITION: On June 26, 2021, a systematic search was performed in Medline, Google Scholar, Google book, and Cochrane Library using the terms: "tumor induced osteomalacia," "oncogenic osteomalacia," "hypophosphatemia." There were no language restrictions. This review was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses criteria. EVIDENCE RESULTS: Overall, 1725 TIO cases were collected. TIO was more frequent in adult men, who showed a higher incidence of fractures compared with TIO women. The TIO-causing neoplasms were identified in 1493 patients. The somatostatin receptor-based imaging modalities have the highest sensitivity for the identification of TIO-causing neoplasms. TIO-causing neoplasms were equally located in bone and soft tissues; the latter showed a higher prevalence of fractures and deformities. The surgery is the preferred TIO definitive treatment (successful in > 90% of patients). Promising nonsurgical therapies are treatments with burosumab in TIO patients with elevated fibroblast growth factor-23 levels, and with radiolabeled somatostatin analogs in patients with TIO-causing neoplasm identified by somatostatin receptor-based imaging techniques. CONCLUSION: TIO occurs preferentially in adult men. The TIO clinical expressiveness is more severe in men as well as in patients with TIO-causing neoplasms located in soft tissues. Treatments with burosumab and with radiolabeled somatostatin analogs are the most promising nonsurgical therapies.