Real-world data of Brazilian adults with X-linked hypophosphatemia (XLH) treated with burosumab and comparison with other worldwide cohorts.

BACKGROUND: Disease-related variants in PHEX cause XLH by an increase of fibroblast growth factor 23 (FGF23) circulating levels, resulting in hypophosphatemia and 1,25(OH)2 vitamin D deficiency. XLH manifests in early life with rickets and persists in adulthood with osseous and extraosseous manifestations. Conventional therapy (oral phosphate and calcitriol) improves some symptoms, but evidence show that it is not completely effective, and it can lead to nephrocalcinosis (NC) and hyperparathyroidism (HPT). Burosumab (anti-FGF23 antibody) has shown to be effective and safety in the clinical trials. METHODS: The current real-world collaborative study evaluated genetic, clinical and laboratory data of XLH Brazilian adult patients treated with burosumab. RESULTS: Nineteen unrelated patients were studied. Patients reported pain, limb deformities and claudication, before burosumab initiation. 78% of them were previously treated with conventional therapy. The severity of the disease was moderate to severe (15 patients with score >5). At the baseline, 3 patients presented NC (16.7%) and 12 HPT (63%). After 16 ± 8.4 months under burosumab, we observed a significant: increase in stature (p = 0.02), in serum phosphate from 1.90 ± 0.43 to 2.67 ± 0.52 mg/dL (p = 0.02); in TmP/GFR from 1.30 ± 0.46 to 2.27 ± 0.64 mg/dL (p = 0.0001), in 1,25 (OH)2 D from 50.5 ± 23.3 to 71.1 ± 19.1 pg/mL (p = 0.03), and a decrease in iPTH from 86.8 ± 37.4 pg/mL to 66.5 ± 31.1 (p = 0.002). Nineteen variants were found (10 novel). HPT tended to develop in patients with truncated PHEX variants (p = 0.06). CONCLUSIONS: This study confirms the efficacy and safety of burosumab on XLH adult patients observed in clinical trials. Additionally, we observed a decrease in iPTH levels in patients with moderate to severe HPT at the baseline.

Performance of collagen-based matrices from Nile tilapia skin: A pilot proteomic study in a murine model of wound healing.

Full-thickness cutaneous trauma, due to the lack of dermis, leads to difficulty in epithelialization by keratinocytes, developing a fibrotic scar, with less elasticity than the original skin, which may have disorders in predisposed individuals, resulting in hypertrophic scar and keloids. Biomedical materials have excellent characteristics, such as good biocompatibility and low immunogenicity, which can temporarily replace traditional materials used as primary dressings. In this work, we developed two dermal matrices based on Nile tilapia collagen, with (M_GAG) and without (M) glycosaminoglycans, using a sugarcane polymer membrane as a matrix support. To assess the molecular mechanisms driving wound healing, we performed qualitative proteomic analysis on the wound bed in an in vivo study involving immunocompetent murine models at 14 and 21 days post-full-thickness skin injury. Gene Ontology and Pathway analysis revealed that both skins were markedly represented by modulation of the immune system, emphasizing controlling the acute inflammation response at 14 and 21 days post-injury. Furthermore, both groups showed significant enrichment of pathways related to RNA and protein metabolism, suggesting an increase in protein synthesis required for tissue repair and proper wound closure. Other pathways, such as keratinization and vitamin D3 metabolism, were also enriched in the groups treated with M matrix. Finally, both matrices improved wound healing in a full post-thick skin lesion. However, our preliminary molecular data reveals that the collagen-mediated healing matrix lacking glycosaminoglycan (M) exhibited a phenotype more favorable to tissue repair, making it more suitable for use before skin grafts.

Prevalence of hyperapolipoprotein B and associations with other cardiovascular risk factors among human immunodeficiency virus-infected patients in Pernambuco, Brazil.

BACKGROUND: Hypertriglyceridemia associated with low high-density lipoprotein (HDL) levels and hypercholesterolemia is the most common metabolic disorder among human immunodeficiency virus (HIV)-infected patients using antiretroviral therapy. This atherogenic profile is associated with increased cardiovascular risk among these patients. Apolipoprotein B (apoB) is a better parameter than low-density lipoprotein (LDL) for evaluating lipids and cardiovascular risk among patients with diabetes and metabolic syndrome, but studies of apoB among HIV-infected patients are scarce. METHODS: A cross-sectional study was conducted to estimate hyperapolipoprotein B (hyperapoB) prevalence and its association with other factors among HIV-infected patients attended in Recife, Pernambuco, Brazil. RESULTS: The prevalence of hyperapoB was 32.4% among 256 patients (62.1% male), with 90 mg/dL as the cutoff point. It was associated with prolonged use (>3 years) of antiretroviral therapy [odds ratio (OR), 3.63; 95% confidence interval (CI), 1.24-10.6], hypertriglyceridemia (OR, 2.45; 95% CI, 1.22-4.91), insulin resistance according to homeostasis model assessment of insulin resistance (HOMA-IR) (OR, 2.12; 95% CI, 1.03-4.35), past history of diabetes (OR, 3.58; 95% CI, 1.0-12.7), and hypertension (OR, 1.98; 95% CI, 0.92-4.28). It was not associated with low HDL levels or self-report lipodystrophy. ApoB was higher in patients with metabolic syndrome according to the National Cholesterol Education Program (NCEP) criteria and in those with higher Framingham scores. CONCLUSIONS: ApoB is a good parameter for evaluating lipid levels in HIV-infected patients with hypertriglyceridemia, among whom LDL measurements may not be appropriate. ApoB might be useful for diagnosing and treating hypertriglyceridemia in this population. The association between hyperapoB and hypertriglyceridemia and diseases relating to insulin resistance among HIV-infected patients suggests that this group of patients presents higher cardiovascular risk.

Risk factors in human immunodeficiency virus/acquired immunodeficiency syndrome patients undergoing antiretroviral therapy in the state of Pernambuco, Brazil: a case-control study.

BACKGROUND: Although human immunodeficiency virus (HIV)-associated lipodystrophy has been reported for more than a decade, there is still considerable uncertainty regarding the mechanisms involved in its pathogenesis. METHODS: A case-control study was performed that aimed to identify the risk factors for lipodystrophy in HIV/acquired immunodeficiency syndrome (AIDS) patients undergoing antiretroviral therapy in Pernambuco, Brazil. RESULTS: Between July and November, 2007, a total of 332 patients were enrolled in the study: 182 cases and 150 controls. The following factors were independently associated with lipodystrophy: Use of stavudine [odds ratio (OR), 4.0; 95% confidence interval (CI), 2.3-6.9], use of didanosine (OR, 1.8; 95% CI, 1.0-3.4), use of lopinavir/ritonavir for less than 3 years (OR, 0.5; 95% CI, 0.2-1.0) and use of nucleoside/nucleotide analogue reverse transcriptase inhibitors (NTRIs) for more than 3 years (OR, 2.9; 95% CI, 1.6-5.2). Other associated factors were: duration of antiretroviral therapy (OR, 4.3; 95% CI, 2.4-7.9) and duration of HIV infection (OR, 2.9; 95% CI, 1.8-4.7). There was no association with the use of protease inhibitor when it was adjusted for the use of NRTIs. CONCLUSION: In this study, factors related to antiretroviral therapy were the main risk factors for lipodystrophy, corroborating the literature, but the findings also point to the need for further exploration into some of these associations, especially with the use of didanosine and lopinavir/ritonavir, which are less frequently reported. Future studies with a larger number of patients and a prospective design could provide valuable information for understanding this disorder.