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.

Body mass index in individuals with HIV infection and factors associated with thinness and overweight/obesity.

A cross-sectional study was conducted using body mass index (BMI) to estimate the prevalence of thinness and overweight/obesity and associated factors in 2,018 individuals with HIV/AIDS attending health services referral centers. The dependent variable was classified as thinness, overweight/obesity and eutrophy. Multinomial logistic regression analyses were performed considering eutrophy as the reference level. The prevalence of thinness was 8.8% and of overweight/obesity, 32.1%. The variables associated with thinness were anemia and CD4 cell count < 200mm³. The variables associated with risk of overweight/obesity were age > 40 years and diabetes, and the variables identified as decreasing likelihood of overweight/obesity were having no long-term partner, smoking, presence of an opportunistic disease, anemia, and albumin levels < 3.5mg/dL. The main nutritional problem observed in this population was overweight and obesity, which were much more prevalent than thinness. Older individuals with diabetes should be targeted for nutritional interventions and lifestyle changes.

Body mass index in individuals with HIV infection and factors associated with thinness and overweight/obesity / Índice de massa corporal em indivíduos com infecção pelo HIV e fatores associados com magreza e sobrepeso/obesidade

A cross-sectional study was conducted using body mass index (BMI) to estimate the prevalence of thinness and overweight/obesity and associated factors in 2,018 individuals with HIV/AIDS attending health services referral centers. The dependent variable was classified as thinness, overweight/obesity and eutrophy. Multinomial logistic regression analyses were performed considering eutrophy as the reference level. The prevalence of thinness was 8.8 percent and of overweight/obesity, 32.1 percent. The variables associated with thinness were anemia and CD4 cell count < 200mm³. The variables associated with risk of overweight/obesity were age > 40 years and diabetes, and the variables identified as decreasing likelihood of overweight/obesity were having no long-term partner, smoking, presence of an opportunistic disease, anemia, and albumin levels < 3.5mg/dL. The main nutritional problem observed in this population was overweight and obesity, which were much more prevalent than thinness. Older individuals with diabetes should be targeted for nutritional interventions and lifestyle changes.

Estudo seccional para estimar a prevalência de magreza e sobrepeso/obesidade e fatores associados em 2.018 indivíduos com HIV/AIDS, atendidos em serviços de referência em Recife, Pernambuco, Brasil, utilizando o índice de massa corporal. A variável dependente foi classificada como magreza, sobrepeso/obesidade e eutrofia. Realizou-se análise de regressão logística multinomial considerando-se como referência os eutróficos. A prevalência de magreza foi de 8,8 por cento e a de sobrepeso/obesidade de 32,1 por cento. Permaneceram associados à magreza ter anemia e contagem de células TCD4 < 200mm³. Os fatores associados à maior chance de sobrepeso/obesidade foram: idade > 40 anos e presença de diabetes, e aqueles inversamente associados com sobrepeso/obesidade: não ter companheiro fixo, tabagismo, história recente de doença oportunista, anemia e níveis de albumina < 3,5mg/dL. O principal desvio nutricional observado foi o sobrepeso/obesidade, superando a magreza. Os indivíduos mais velhos com diabetes devem ser alvos de intervenções nutricionais e de estilo de vida.

First description of pseudohypoparathyroidism with frontal lobe calcification and normal serum calcium at the initial manifestation in an otherwise healthy seven-year-old girl.

Pseudohypoparathyroidism (PHP) is characterized by resistance to the peripheral action of parathyroid hormone. We present a case of a seven-year-old girl who was admitted at the service of Instituto Materno Infantil de Pernambuco, IMIP, with motor episodes affecting the arms. Her calcium level was normal. Computed tomography showed calcifications in frontal lobes and basal ganglia. After six years: calcium was 5.5 mg/dL; phosphorus, 8.3 mg/dL and serum parathyroid hormone was 1,318 pg/mL. Pseudohypoparathyroidism diagnosis was considered. This is the first description of a case of pseudohypoparathyroidism without Albright's stigma, with cerebral calcification, and no calcium abnormalities at the initial clinical manifestation.

Comparison between the Framingham and prospective cardiovascular of Münster scores for risk assessment of coronary heart disease in human immunodeficiency virus-positive patients in Pernambuco, Brazil.

BACKGROUND: The Framingham score is used in most studies on human immunodeficiency virus (HIV)-positive patients to estimate the risk for coronary heart disease; however, it may have some limitations for detecting risk among these individuals. OBJECTIVE: The aim of this study was to evaluate the agreement between the Framingham and Prospective Cardiovascular of Münster (PROCAM) scores among HIV-positive individuals and to investigate the factors associated with disagreement between the two scores. METHOD: A cross-sectional study was conducted in a population of HIV/acquired immunodeficiency syndrome (AIDS) patients attending the outpatient's clinics of two reference centers for HIV/AIDS in Pernambuco, Brazil. Agreement between the Framingham and PROCAM scores was evaluated using the kappa index. From this analysis, a variable called "disagreement between scores" was created, and univariate and multivariate analysis were performed to investigate the factors associated with this variable. RESULTS: The prevalence of low, moderate, and high risk were, respectively, 78.7%, 13.5%, and 7.8% by Framingham score and 88.5%, 4.3%, and 7.2% by PROCAM (kappa = 0.64, P ≤ 0.0001). Agreement in the subgroup with metabolic syndrome by the International Diabetes Federation (IDF) (kappa = 0.51, P ≤ 0.0001) and the National Cholesterol Education Program (NCEP) (kappa = 0.59, P ≤ 0.0001) criteria was moderate. The Framingham score identified greater proportion of women with moderate risk. Factors independently associated with disagreement were: smoking, sex, age, low-density lipoprotein cholesterol, diastolic blood pressure, and metabolic syndrome. CONCLUSION: There was a good agreement between the Framingham and PROCAM scores in HIV-positive patients, but a higher proportion of moderate-high risk was identified by the Framingham score. This disagreement should be evaluated in cohort studies to observe clinical outcomes over the course of time.

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.

Bone mineral density in HIV-infected women taking antiretroviral therapy: a systematic review.

There is a high prevalence of osteoporosis in HIV-infected patients. Initially described in HIV-positive men, studies have also demonstrated a high prevalence of osteoporosis in HIV-infected women. It would appear that antiretroviral therapy (ART) plays an important role in the pathogenesis of osteoporosis in HIV-infected patients, although little is known about its importance in relation to osteoporosis and fractures in HIV-positive women. The aim of this systematic review was to evaluate the frequency of bone loss, bone mineral density (BMD) and fractures in HIV-positive women taking ART or protease inhibitors (PI). After screening 597 citations from the databases of PubMed, EMBASE and Lilacs, five studies were selected for the review. A difference was demonstrated of over 3% in the BMD at the femoral neck of HIV-positive women taking PI/ART. No difference was registered in the BMD at the lumbar spine between users and non-users of PI/ART. The lack of studies has made it impossible to reach any conclusion regarding the occurrence of fractures.

Bone mineral density in HIV-infected women taking antiretroviral therapy: a systematic review / Densidade mineral óssea em mulheres infectadas pelo vírus do HIV e tratadas com terapia antirretroviral: uma revisão sistemática

There is a high prevalence of osteoporosis in HIV-infected patients. Initially described in HIV-positive men, studies have also demonstrated a high prevalence of osteoporosis in HIV-infected women. It would appear that antiretroviral therapy (ART) plays an important role in the pathogenesis of osteoporosis in HIV-infected patients, although little is known about its importance in relation to osteoporosis and fractures in HIV-positive women. The aim of this systematic review was to evaluate the frequency of bone loss, bone mineral density (BMD) and fractures in HIV-positive women taking ART or protease inhibitors (PI). After screening 597 citations from the databases of PubMed, EMBASE and Lilacs, five studies were selected for the review. A difference was demonstrated of over 3 percent in the BMD at the femoral neck of HIV-positive women taking PI/ART. No difference was registered in the BMD at the lumbar spine between users and non-users of PI/ART. The lack of studies has made it impossible to reach any conclusion regarding the occurrence of fractures.

A prevalência de osteoporose é elevada em indivíduos infectados pelo HIV. Inicialmente descrita em homens HIV-positivos, estudos demonstraram alta prevalência de osteoporose também em mulheres HIV-positivas. A terapia antirretroviral parece exercer papel importante na patogênese da osteoporose dos indivíduos com HIV. Pouco se sabe sobre sua importância para a osteoporose e fraturas nas mulheres HIV-positivas. Esta revisão objetivou avaliar a frequência de perda de massa óssea, densidade mineral óssea (DMO) e fraturas em mulheres HIV-positivas em uso de terapia antirretroviral (TARV) ou inibidores de protease (IP). Após busca nos bancos de dados PubMed, EMBASE e Lilacs, de 597 citações, cinco estudos permaneceram na revisão. Demonstrou-se haver uma diferença superior a 3 por cento na DMO no colo do fêmur de mulheres HIV-positivas em uso de IP/TARV. Não se evidenciou diferença na DMO da coluna lombar entre usuárias e não usuárias de IP/TARV. A escassez de estudos impossibilitou qualquer conclusão sobre a ocorrência de fraturas.

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.