FGF23 Beyond the Kidney: A New Bone Mass Regulator in the General Population.

Clinical studies investigating the relationship between fibroblast growth factor 23 (FGF23) and bone mass are controversial, especially in the healthy renal population. Our study is one of the forefronts investigating the relationship between FGF23 and bone mass parameters in the general population, according to age, sex, menopausal, and nutritional status. Cross-sectional study enrolling 123 volunteers between 20-80 years of age without primary osteoporosis under treatment nor secondary osteoporosis, where bone mass (bone mineral density-BMD, bone mineral content-BMC; assessed by Dual X-Ray Absorptiometry-DXA), body composition (DXA evaluation), and also the serum levels of FGF23, parathormone (PTH), 25(OH)D, bone resorption marker C-terminal telopeptide of type I collagen (CTx) and leptin were determined. FGF23 was negatively and independently associated with BMD and/or BMC in all groups. FGF23 contributed to up to 10% (p <0.05) of femoral neck BMD variance in postmenopausal women, but was not an accurate discriminator of normal versus low bone mass (AUC=0.622±0.076). FGF23 did not correlate with 25(OH)D, CTx, body weight, body composition parameters or leptin. FGF23 was independently associated with PTH in premenopausal women and men only. FGF23 was negatively associated with bone mass parameters in both sexes, but was not a fine discriminator between normal bone mass and osteopenia/osteoporosis. The mechanism through which FGF23 acts upon the bone seems independent of the nutritional status, requiring further investigation.

Management of Labour and Delivery in a Patient With Acquired Factor VII Deficiency With Inhibitor: A Case Report.

BACKGROUND: Acquired factor VII (FVII) deficiency with inhibitor increases the risk of hemorrhage during pregnancy. However, there are no published reports guiding its management in the peripartum period. CASE: A 24-year-old woman with inhibitory antibodies to FVII delivered at 34 weeks of gestation. The patient was administered recombinant factor VIIa (rFVIIa) and tranexamic acid. There were no bleeding-related complications; however, the FVII level was supratherapeutic. The patient returned during a second pregnancy. A reduced dose of rFVIIa was administered. The delivery was complicated by postpartum hemorrhage, which resolved with the addition of uterotonic agents. CONCLUSION: Recombinant FVIIa and tranexamic acid offer an effective peripartum treatment in women with inhibitory antibody to FVII. Further research should delineate the optimal time of administration.

Coincidence or Causality: Parathyroid Carcinoma in Chronic Kidney Disease-Case Report and Literature Review.

Parathyroid carcinoma (PC) associated with primary hyperparathyroidism (PHPT) has been well investigated in recent years. Data regarding PC evolution in secondary hyperparathyroidism (SHPT) due to chronic kidney disease (CKD) are, however, scarce. Most features that raise the suspicion of PC in PHPT are part of the usual SHPT evolution in CKD, mirroring the natural changes undergone by the parathyroid glands. Therefore, pre-surgically establishing the malignant or benign character of the lesions is cumbersome. We present two cases of PC in end-stage renal disease, one of which was bilateral, diagnosed after total parathyroidectomy in a high-volume parathyroid surgery center. A literature review of the data was also performed. A systematic search of the PubMed/MEDLINE database until January 2024 identified 42 cases of PC associated with SHPT. Understanding the PC features in CKD might improve associated bone and mineral disease management, and reduce the risk of metastasis, parathyromatosis, or recurrence. Irradiation, prolonged immunosuppression, long dialysis vintage, and genotype may predispose to the malignant transformation of chronically stimulated parathyroids. Despite postsurgical diagnosis, favorable outcomes occurred when distant metastases were absent, even without "en bloc" resection. Further research is warranted to delineate specific diagnostic and therapeutic approaches tailored to this particular patient subpopulation.

Body composition, adipokines, FGF23-Klotho and bone in kidney transplantation: Is there a link?

BACKGROUND: Kidney transplantation-associated mineral and bone disorder (KT-MBD) still represents a black box on the long-term due to scarce available data. We aimed to investigate the impact of non-classical bone regulating factors (body composition, adipokines, inflammatory markers, fibroblast growth factor 23-FGF23 and α-Klotho) in long-standing kidney transplant (KT) recipients compared to the general population. METHODS: Our cross-sectional study, enrolling 59 KT patients and age, sex and body mass index-matched healthy general population volunteers, assessed the predictive role of the body composition, serum adipokines (leptin, adiponectin, resistin), inflammatory markers (erythrocyte sedimentation rate, C-reactive protein) and parathyroid hormone (PTH)-FGF23/α-Klotho axis upon bone mineral density (BMD) and osteocalcin, using correlation and linear multiple regression. RESULTS: The 59 KT recipients (mean transplantation span of 57.7 ± 7.2 months) had similar body composition but significantly lower BMD (p < 0.01) compared to the general population group. Total lean mass was independently associated with BMD in both groups. In KT patients, age, time spent on dialysis and PTH were the main negative independent predictors of BMD, after adjusting for possible confounders. Resistin and α-Klotho also negatively predicted lumbar bone density (p < 0.001), while adiponectin and α-Klotho positively predicted osteocalcin levels (p < 0.001) in KT recipients, independently of inflammatory markers. No significant associations were found between FGF23 and bone parameters in any of the groups. CONCLUSIONS: Age, PTH, time on dialysis and lean mass are among the main bone density predictors in long-standing KT patients. The bone impact of adipokine dysregulation and of α-Klotho merits further investigations in KT-MBD. Preserving lean mass for improved bone outcomes should be part of KT-MBD management on the long-term.

New insights into the metabolic-bone crosstalk in active acromegaly.

INTRODUCTION: Body composition (BC) and adipokines share bone active properties and display an altered profile in acromegaly. The fibroblast growth factor 23 (FGF23)/α-Klotho system, also involved in bone metabolism, is upregulated in growth hormone (GH) excess states. Hence, we aimed to investigate their impact on bone in active acromegaly, compared to controls. MATERIAL AND METHODS: BC, bone mineral density (BMD) (via dual X-ray absorptiometry), serum adipokines (leptin, adiponectin, resistin), parathyroid hormone (PTH), FGF23, α-Klotho, and osteocalcin were assessed in a cross-sectional study enrolling 35 patients with active acromegaly (Acro), compared to 35 sex, age, and body mass index (BMI) one-to-one matched healthy controls (CTL). RESULTS: The Acro group had higher bone density scores (p < 0.05), lower visceral fat depots (p = 0.011), and lower serum leptin (p < 0.001) but elevated adiponectin (p < 0.001) and resistin (p = 0.001) concentrations when compared to the CTL group. α-Klotho was not related to the GH/IGF1 axis in the Acro group. Resistin was higher in both diabetic and non-diabetic Acro compared to CTL (p < 0.05). Age and BC were the main independent BMD predictors in regression analysis in both groups, while IGF1 was a positive predictor of osteocalcin levels in the Acro (ß = 0.48, p = 0.006). The correlations between adipokines, the FGF23/α-Klotho system, and bone parameters, respectively, were lost after adjusting for age and BC. CONCLUSIONS: Age and BC were the main independent BMD predictors in the acromegalic patients with active disease, while IGF1 was independently associated with serum osteocalcin concentrations. The role of α-Klotho in evaluating acromegaly and the associated osteopathy in the long-term appears to be limited. Our study is among the first to report significant serum resistin changes in patients with active acromegaly, opening new insights in the GH-mediated insulin resistance. The GH-resistin relationship merits further investigations.

Paraquat induces oxidative stress, neuronal loss in substantia nigra region and parkinsonism in adult rats: neuroprotection and amelioration of symptoms by water-soluble formulation of coenzyme Q10.

BACKGROUND: Parkinson's disease, for which currently there is no cure, develops as a result of progressive loss of dopamine neurons in the brain; thus, identification of any potential therapeutic intervention for disease management is of a great importance. RESULTS: Here we report that prophylactic application of water-soluble formulation of coenzyme Q10 could effectively offset the effects of environmental neurotoxin paraquat, believed to be a contributing factor in the development of familial PD. In this study we utilized a model of paraquat-induced dopaminergic neurodegeneration in adult rats that received three weekly intra-peritoneal injections of the herbicide paraquat. Histological and biochemical analyses of rat brains revealed increased levels of oxidative stress markers and a loss of approximately 65% of dopamine neurons in the substantia nigra region. The paraquat-exposed rats also displayed impaired balancing skills on a slowly rotating drum (rotorod) evidenced by their reduced spontaneity in gait performance. In contrast, paraquat exposed rats receiving a water-soluble formulation of coenzyme Q10 in their drinking water prior to and during the paraquat treatment neither developed neurodegeneration nor reduced rotorod performance and were indistinguishable from the control paraquat-untreated rats. CONCLUSION: Our data confirmed that paraquat-induced neurotoxicity represents a convenient rat model of parkinsonian neurodegeneration suitable for mechanistic and neuroprotective studies. This is the first preclinical evaluation of a water-soluble coenzyme Q10 formulation showing the evidence of prophylactic neuroprotection at clinically relevant doses.

Primary and secondary prevention of preterm birth: a review of systematic reviews and ongoing randomized controlled trials.

BACKGROUND: Preterm birth (PTB) is a leading cause of perinatal morbidity and mortality. Interventions aimed at preventing PTB can be classified as primary, secondary, or tertiary prevention. OBJECTIVE: To conduct a review of systematic reviews on the effectiveness and safety of primary and secondary preterm birth prevention interventions. SEARCH STRATEGY: A systematic literature search of the Cochrane, PubMed/Medline, EMBASE and CINAHL databases was conducted on 2 September 2015, and updated on 21 November 2016. SELECTION CRITERIA: We included any published systematic review of randomized controlled trials (RCTs) or individual patient data (IPD) of RCTs related to primary or secondary prevention of PTB, published between 2005-2016 where gestational age at birth (of any interval) was a pre-specified outcome. Individual trials and non-systematic reviews were not eligible. DATA COLLECTION AND ANALYSIS: The population of interest was all pregnant women, regardless of PTB risk. The primary outcome was PTB < 37 weeks. MAIN RESULTS: In total, 112 reviews were included in this study. Overall there were 49 Cochrane and 63 non-Cochrane reviews. Eight were individual participant data (IPD) reviews. Sixty reviews assessed the effect of primary prevention interventions on risk of PTB. Positive effects were reported for lifestyle and behavioural changes (including diet and exercise); nutritional supplements (including calcium and zinc supplementation); nutritional education; screening for lower genital tract infections. Eighty-three systematic reviews were identified relating to secondary PTB prevention interventions. Positive effects were found for low dose aspirin among women at risk of preeclampsia; clindamycin for treatment of bacterial vaginosis; treatment of vaginal candidiasis; progesterone in women with prior spontaneous PTB and in those with short midtrimester cervical length; L-arginine in women at risk for preeclampsia; levothyroxine among women with tyroid disease; calcium supplementation in women at risk of hypertensive disorders; smoking cessation; cervical length screening in women with history of PTB with placement of cerclage in those with short cervix; cervical pessary in singleton gestations with short cervix; and treatment of periodontal disease. CONCLUSION: The overview serves as a guide to current evidence relevant to PTB prevention. Only a few interventions have been demononstrated to be effective, including cerclage, progesterone, low dose aspirin, and lifestyle and behavioural changes. For several of the interventions evaluated, there was insufficient evidence to assess whether they were effective or not.

Research prioritization of interventions for the primary prevention of preterm birth: An international survey.

OBJECTIVE: To identify research priorities of interventions for the primary prevention of preterm birth (PTB), by conducting an international stakeholder survey. STUDY DESIGN: A prospective cross-sectional online survey was conducted in November 2016. Fifteen interventions to prevent spontaneous PTB were identified and ranked by stakeholders (n = 159) in the field of maternal and perinatal health research, using nine equally weighted criteria. Medians and interquartile ranges (IQRs) were calculated and the interventions ranked accordingly. RESULTS: Respondents to the survey were from 46 different countries, mostly from low and middle-income countries (62%, 99/159) and were mainly clinicians (80%, 127/159). Of the fifteen interventions ranked, the following five were identified as research priorities in the primary prevention of PTB: dietary counselling and nutritional education, risk scoring, vitamin D supplementation, exercise and antioxidant supplementation. CONCLUSION: We have identified research priorities of interventions to prevent spontaneous PTB through a global stakeholder survey. The interventions prioritized in this exercise can be used by researchers, grant funding bodies and research-policy decision makers to inform calls on future clinical trials or individual patient data meta-analyses on the primary prevention of PTB.

Sublingual desmopressin is efficient and safe in the therapy of lithiasic renal colic.

PURPOSE: To evaluate the effects of newer sublingual desmopressin administration in lithiasic renal colic, alone or combined with a nonsteroidal anti-inflammatory drug (NSAID). METHODS: Prospective single-blind study including an initial number of 249 patients with lithiasic renal colic was randomized as follows: group NSAID (71 patients) received ketorolac tromethamine (ketorolac) 30 mg im and sublingual placebo (vitamin C), groups D1 and D2 (57 and 62 patients) received sublingual desmopressin (Minirin Melt), 60 and 120 µg, respectively, whereas group C (59 patients) received a combination of 30 mg im ketorolac and 60 µg sublingual desmopressin. Pain intensity was assessed using the visual analogue scale before and thirty minutes after drug administration. Patients experiencing pain aggravation were rescued and excluded from the study. RESULTS: Dropout incidence was higher in the NSAID group than in the groups treated with desmopressin in monotherapy or combined with ketorolac (p < 0.05). Pain intensity was diminished at least as potently by the monotherapy with desmopressin and ketorolac. The higher dose of desmopressin and the combination therapy decreased pain intensity with 56 and 59%, respectively, significantly more than the 47% decrease obtained with ketorolac alone (p < 0.05 and p < 0.001). Mean pain decrease was higher in the combination group (C) than in the NSAID or D1 groups (p < 0.001 and p < 0.05, respectively), suggesting drug additivity. Patients did not experience severe side effects. CONCLUSIONS: Sublingual desmopressin is at least as potent as NSAID in the treatment of lithiasic renal colic. The combination of sublingual desmopressin and NSAID has additive analgesic effects.