An update on clinical presentation and responses to therapy of patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH).

Pathogenic variants in solute carrier family 34, member 3 (SLC34A3), the gene encoding the sodium-dependent phosphate cotransporter 2c (NPT2c), cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH). Here, we report a pooled analysis of clinical and laboratory records of 304 individuals from 145 kindreds, including 20 previously unreported HHRH kindreds, in which two novel SLC34A3 pathogenic variants were identified. Compound heterozygous/homozygous carriers show above 90% penetrance for kidney and bone phenotypes. The biochemical phenotype for heterozygous carriers is intermediate with decreased serum phosphate, tubular reabsorption of phosphate (TRP (%)), fibroblast growth factor 23, and intact parathyroid hormone, but increased serum 1,25-dihydroxy vitamin D, and urine calcium excretion causing idiopathic hypercalciuria in 38%, with bone phenotypes still observed in 23% of patients. Oral phosphate supplementation is the current standard of care, which typically normalizes serum phosphate. However, although in more than half of individuals this therapy achieves correction of hypophosphatemia it fails to resolve the other outcomes. The American College of Medical Genetics and Genomics score correlated with functional analysis of frequent SLC34A3 pathogenic variants in vitro and baseline disease severity. The number of mutant alleles and baseline TRP (%) were identified as predictors for kidney and bone phenotypes, baseline TRP (%) furthermore predicted response to therapy. Certain SLC34A3/NPT2c pathogenic variants can be identified with partial responses to therapy, whereas with some overlap, others present only with kidney phenotypes and a third group present only with bone phenotypes. Thus, our report highlights important novel clinical aspects of HHRH and heterozygous carriers, raises awareness to this rare group of disorders and can be a foundation for future studies urgently needed to guide therapy of HHRH.

Determinants of health-related quality of life and global functioning and health in axSpA, pSpA, and PsA: results from the ASAS-PerSpA study.

OBJECTIVES: We aim to identify determinants of health-related quality of life (HRQoL) and global functioning and health (GH) in axial spondyloarthritis (axSpA), peripheral spondyloarthritis (pSpA), and psoriatic arthritis (PsA). METHODS: ASAS-perSpA study data were analyzed. Models for the three patient groups were performed separately to explore factors associated with HRQoL and GH, assessed by EQ-5D and ASAS-HI, respectively. RESULTS: The analyses included 4185 patients: 2719 with axSpA, 433 with pSpA, and 1033 with PsA.In axSpA, disease activity (DA) (ß=-0.061), physical function (ß=-0.041), female sex (ß=-0.019), and fibromyalgia (ß=-0.068) were associated with worse HRQoL; age (ß = 0.001) and university education (ß = 0.014) with better HRQoL. In pSpA, DA (ß=-0.04) and physical function (ß=-0.054) were associated with worse HRQoL. In PsA, DA (ß=-0.045), physical function (ß=-0.053), axial disease (ß=-0.041), and female sex (ß=-0.028) were associated with worse HRQoL.In axSpA, DA (ß = 0.889), physical function (ß = 0.887), peripheral disease (ß = 0.564), female sex (ß = 0.812) and fibromyalgia (ß = 1.639) were associated with worse GH; age (ß=-0.013) and university education (ß=-0.274) with better GH. In pSpA, physical function (ß = 1.142), and female sex (ß = 1.060) were associated with worse GH; university education (ß=-0.611) with better GH. In PsA, DA (ß = 0.703), physical function (ß = 1.025), axial involvement (ß = 0.659), female sex (ß = 0.924), and fibromyalgia (ß = 1.387) were associated with worse GH; age (ß=-0.024) and university education (ß=-0.856) with better GH. CONCLUSIONS: DA and physical function are major HRQoL and GH determinants across spondyloarthritis types, and clinical characteristics and sociodemographic factors play an important role, highlighting the importance of a holistic approach for individual patients.

Topical Administration of a Marine Oil Rich in Pro-Resolving Lipid Mediators Accelerates Wound Healing in Diabetic db/db Mice through Angiogenesis and Macrophage Polarization.

Impaired wound healing in patients with type 2 diabetes (DM2) is characterized by chronic inflammation, which delays wound closure. Specialized pro-resolving lipid mediators (SPMs) are bioactive molecules produced from essential polyunsaturated fatty acids (PUFAs), principally omega-3 docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). SPMs are potent regulators of inflammation and have been used to suppress chronic inflammation in peripheral artery disease, non-alcoholic fatty liver disease, and central nervous system syndromes. LIPINOVA® is a commercially available safe-grade nutritional supplement made from a fractionated marine lipid concentrate derived from anchovy and sardine oil that is rich in SPMs and EPA, as well as DHA precursors. Here, we assessed the effect of LIPINOVA® in wound dressing applications. LIPINOVA® showed biocompatibility with keratinocytes and fibroblasts, reduced the abundance of pro-inflammatory macrophages (Mφ1), and promoted in vitro wound closure. Daily application of the marine oil to open wounds made by punch biopsy in db/db mice promoted wound closure by accelerating the resolution of inflammation, inducing neoangiogenesis and Mφ1/Mφ2 macrophage polarization. In conclusion, LIPINOVA® displays pro-resolutive properties and could be exploited as a therapeutic agent for the treatment of diabetic ulcers.

Targeted Isolation of Anti-inflammatory Lignans from Justicia aequilabris by Molecular Networking Approach.

Herein, the isolation of secondary metabolites from the aerial parts of Justicia aequilabris guided by HPLC-MSn and molecular networking analyses is reported. Twenty-two known compounds were dereplicated. Three new lignans (aequilabrines A-C (1-3)) and three known compounds (lariciresinol-4'-O-ß-glucose (4), roseoside (5), and allantoin (6)) were obtained. The anti-inflammatory activity of compounds 1-3 was evaluated in vitro by inhibiting the nitric oxide production (NO) and pro-inflammatory activity on the cytokine IL-1ß. Compounds 2 and 3 showed significant inhibitory activity against NO production, with IC50 values of 9.1 and 7.3 µM, respectively. The maximum inhibition of IL-1ß production was 23.5% (1), 27.3% (2), and 32.5% (3).

Motor Rehabilitation of Upper Limbs Using a Gesture-Based Serious Game: Evaluation of Usability and User Experience.

Objective: Gesture-based serious games can be based on playful and interactive scenarios to enhance user engagement and experience during exercises, thereby increasing efficiency in the motor rehabilitation process. This study aimed to develop the Rehabilite Game (RG) as a complementary therapy tool for upper limb rehabilitation in clinics and home environments and to evaluate aspects of usability and user experience of it. Materials and Methods: The evaluation consisted of the use of a gesture-based serious game with motor rehabilitation sessions managed in a web platform. Thirty-three participants were recruited (21 physiotherapists and 12 patients). The protocol allowed each participant to have the experience of playing sessions with different combinations of settings. The User Experience Questionnaire (UEQ) was used to evaluate aspects of usability and user experience. The study was approved by the Research Ethics Board of the Federal University of Piaui (number 3,429,494). Results: The level of satisfaction with the RG was positive, with an excellent Net Promoter Score for 85.7% of physiotherapists and 100% of patients. All six UEQ scales (attractiveness, perspicuity, efficiency, dependability, stimulation, and novelty) reflected acceptance. Conclusion: The study demonstrated that, according to the results obtained in the experiments, the RG had positive feedback from physiotherapists and patients, indicating that the game can be used in a clinical trial to be compared with other rehabilitation techniques.

PCOS: A Chronic Disease That Fails to Produce Adequately Specialized Pro-Resolving Lipid Mediators (SPMs).

INTRODUCTION: Polycystic ovary syndrome (PCOS) is an endocrinological disorder that affects 5-15% of women of their reproductive age and is a frequent cause of infertility. Major symptoms include hyperandrogenism, ovulatory dysfunction, and often obesity and/or insulin resistance. PCOS also represents a state of chronic low-grade inflammation that is closely interlinked with the metabolic features. "Classical" pro-inflammatory lipid mediators such as prostaglandins (PG), leukotrienes (LT), or thromboxanes (TX) are derived from arachidonic acid (AA) and are crucial for the initial response. Resolution processes are driven by four families of so-called specialized pro-resolving mediators (SPMs): resolvins, maresins, lipoxins, and protectins. The study aimed to establish lipid mediator profiles of PCOS patients compared to healthy women to identify differences in their resolutive and pro-inflammatory lipid parameters. MATERIAL AND METHODS: Fifteen female patients (18-45 years) were diagnosed with PCOS according to Rotterdam criteria, and five healthy women, as a comparator group, were recruited for the study. The main outcome measures were: pro-inflammatory lipid mediators (PG, LT, TX) and their precursor AA, SPMs (resolvins, maresins, protectins, lipoxins), their precursors EPA, DHA, DPA, and their active biosynthesis pathway intermediates (18-HEPE, 17-HDHA, 14-HDHA). RESULTS: The level of pro-inflammatory parameters in serum was significantly higher in PCOS-affected women. The ratio (sum of pro-inflammatory molecules)/(sum of SPMs plus hydroxylated intermediates) reflecting the inflammatory state was significantly lower in the group of healthy women. CONCLUSION: There is a strong pro-inflammatory state in PCOS patients. Further research will clarify whether supplementation with SPMs or their precursors may improve this state.

Production and analysis of capsules containing microorganisms consortiated for future application in petroleum bioremediation.

Oil spills cause severe environmental and economic impacts, so the use of bioremediation techniques has been widely studied to solve this problem. Due to its complex composition, the oil prevents the full action of microorganisms, and in this way, the microbial consortium encapsulation technique is an innovation in the use of bacteria and biomass in the face of possible oil degradation, with the possibility of overcoming techniques such as bio-enhancement and biostimulation in the face of factors such as nutrient availability, oxygenation and temperature. Therefore, this work aims to produce capsules containing microbiological consortium and analyze its characteristics using the techniques TGA, DSC, FESEM, viable cell count, emulsification index and surface tension, in order to propose the best conditions to be applied. TGA and DSC results showed that the capsules have thermal stability in the range of 25-40 °C. Viable cell counts were more effective in capsules containing 1% (w/v) sodium alginate, and the emulsification index showed a large increase (80%) from day 5, as well as surface tension had a large drop (48%) in the same period. The increase in the emulsification index is caused by the increase in the production of biosurfactants (amphipathic molecules) by the bacteria consortium and this offers a greater contact between the microorganisms and the oil, providing best conditions for the degradation of oil. Therefore, all analyzes showed excellent results for future application in oil spills.

Phenotypic characterization of X-linked hypophosphatemia in pediatric Spanish population.

BACKGROUND: X-linked hypophosphatemia (XLH) is a hereditary rare disease caused by loss-of-function mutations in PHEX gene leading tohypophosphatemia and high renal loss of phosphate. Rickets and growth retardation are the major manifestations of XLH in children, but there is a broad phenotypic variability. Few publications have reported large series of patients. Current data on the clinical spectrum of the disease, the correlation with the underlying gene mutations, and the long-term outcome of patients on conventional treatment are needed, particularly because of the recent availability of new specific medications to treat XLH. RESULTS: The RenalTube database was used to retrospectively analyze 48 Spanish patients (15 men) from 39 different families, ranging from 3 months to 8 years and 2 months of age at the time of diagnosis (median age of 2.0 years), and with XLH confirmed by genetic analysis. Bone deformities, radiological signs of active rickets and growth retardation were the most common findings at diagnosis. Mean (± SEM) height was - 1.89 ± 0.19 SDS and 55% (22/40) of patients had height SDS below-2. All cases had hypophosphatemia, serum phosphate being - 2.81 ± 0.11 SDS. Clinical manifestations and severity of the disease were similar in both genders. No genotype-phenotype correlation was found. Conventional treatment did not attenuate growth retardation after a median follow up of 7.42 years (IQR = 11.26; n = 26 patients) and failed to normalize serum concentrations of phosphate. Eleven patients had mild hyperparathyroidism and 8 patients nephrocalcinosis. CONCLUSIONS: This study shows that growth retardation and rickets were the most prevalent clinical manifestations at diagnosis in a large series of Spanish pediatric patients with XLH confirmed by mutations in the PHEX gene. Traditional treatment with phosphate and vitamin D supplements did not improve height or corrected hypophosphatemia and was associated with a risk of hyperparathyroidism and nephrocalcinosis. The severity of the disease was similar in males and females.

Cuidados paliativos nas mídias sociais: revisão integrativa de literatura / Palliative care in social media: integrative literature review / Atención paliativa en medios sociales: revisión integrativa de la literatura

Este artigo traz o estudo realizado com o objetivo de identificar as publicações sobre como os cuidados paliativos são abordados nas mídias sociais. Trata-se de uma revisão integrativa de literatura, com pesquisa de artigos nas bases Medical Literature Analysis and Retrieval System Online (Medline), Literatura Latino Americana e do Caribe em Ciências da Saúde (Lilacs) e Scientific Eletronic Library Online (SciELO), em português, inglês e espanhol. Foram selecionados quinze artigos que atendiam aos critérios de seleção propostos, e são aqui apresentados por meio da construção de um quadro sinóptico, contendo título do estudo, periódico, ano de publicação e abordagem dos cuidados paliativos nas mídias sociais. Os resultados dos estudos demonstram que os cuidados paliativos necessitam ser melhor difundidos nas mídias sociais. Entretanto, tal evolução deve ocorrer com cautela, de modo a evitar riscos de comprometer a qualidade das informações e a respeitar questões éticas que envolvem pacientes e profissionais de saúde. Cabe destacar o papel do enfermeiro em ações de educação em saúde relacionadas com cuidados paliativos.

The study presented in this article aims to identify publications which reveal how palliative care is approached on social media. It is an integrative literature review, using search of articles in the bases Medical Literature Analysis and Retrieval System Online (Medline), Latin American and Caribbean Health Sciences Literature (Lilacs) and Scientific Electronic Library Online (SciELO), in Portuguese, English and Spanish languages. Fifteen articles that met the proposed selection criteria were selected, and they are presented here through the construction of a synoptic table, containing the title of the study, the journal in which it was published, its publication date and the specific approaches to palliative care in social media. The results of the studies demonstrate that the palliative care needs to be better disseminated on social media. However, caution should be taken while such dissemination occuring, in order to prevent risks damaging the quality of information and to follow ethical issues involving patients and health professionals. The role of nurses in health education actions regarding the palliative care should be highlighted.

El estudio presentado en este artículo tiene el objetivo de identificar publicaciones sobre cómo se aborda el cuidado paliativo en las redes sociales. Es una revisión literaria integrativa, haciendo una búsqueda de artículos en las bases del Medical Literature Analysis and Retrieval System Online (Medline), Literatura Latinoamericana y del Caribe en Ciencias de la Salud (Lilacs) y Scientific Eletronic Library Online (SciELO), en portugués, inglés y español. Se seleccionaron quince artículos que cumplían los criterios de selección propuestos, y ellos son presentados aquí a través de la construcción de un cuadro sinóptico, que contiene el título del estudio, la revista en la cual ha sido publicado, el año de publicación y el abordaje de los cuidados paliativos en las redes sociales. Los resultados de los estudios demuestran que los cuidados paliativos deben ser mejor difundidos en las redes sociales. Sin embargo, dicha difusión debe ocurrir con precaución para evitar riesgos de perjudicar la calidad de la información y para cumplir las cuestiones éticas que involucran pacientes y profesionales de la salud. El papel de los enfermeros y de las enfermeras en las acciones de educación en salud relacionadas con cuidados paliativos debe ser destacado.

Pro resolving inflammatory effects of the lipid mediators of omega 3 fatty acids and its implication in SARS COVID-19.

COVID-19 is a new disease caused by coronavirus SARS-CoV-2. It was first described in 2019, developed into an epidemic in January 2020 and has spread the global to the present COVID-19 pandemic. Specialized pro­resolving mediators (SPMs) may play a new role in the management of this lung disease because SPM actively stimulate the resolution of infectious inflammation and are organ protective in animal disease models. Many tissues have been suitable targets for treating inflammation with SPMs or their active precursors 18-HEPE, 17-HDHA and the 14-HDHA, in order to elicit dynamic resolution of inflammation. Here we discuss the possible mode of action of these substances in the management of SARS Covid 19.

Why we should use topological data analysis in ageing: Towards defining the "topological shape of ageing".

Living systems are subject to the arrow of time; from birth, they undergo complex transformations (self-organization) in a constant battle for survival, but inevitably ageing and disease trap them to death. Can ageing be understood and eventually reversed? What tools can be employed to further our understanding of ageing? The present article is an invitation for biologists and clinicians to consider key conceptual ideas and computational tools (known to mathematicians and physicists), which potentially may help dissect some of the underlying processes of ageing and disease. Specifically, we first discuss how to classify and analyse complex systems, as well as highlight critical theoretical difficulties that make complex systems hard to study. Subsequently, we introduce Topological Data Analysis - a novel Big Data tool - which may help in the study of complex systems since it extracts knowledge from data in a holistic approach via topological considerations. These conceptual ideas and tools are discussed in a relatively informal way to pave future discussions and collaborations between mathematicians and biologists studying ageing.

Structure Elucidation and Absolute Configuration Determination of Nortriterpenoids from Picramnia glazioviana.

In this study, HPLC-PDA-HRMS-SPE-NMR data were used for initial analysis of the CH2Cl2 fraction of an EtOH extract of the leaves of Picramnia glazioviana. The HRMS, UV, and NMR data obtained from the HPLC-PDA-HRMS-SPE-NMR analysis were used to direct semipreparative HPLC isolation toward nortriterpenoids, which resulted in the isolation of 18 new and highly oxygenated nortriterpenoids (1-3, 5-10, 12-19, and 21), named picravianes C-T. Their structures were determined on the basis of analysis of UV, HRMS, and 2D NMR spectroscopic data, including determination of the relative configuration on the basis of coupling pattern analysis and nuclear Overhauser effect correlations. The absolute configurations of compounds 7, 9, 10, 14, 15, 17, 18, 19, and 21 were assigned using electronic circular dichroism data, and the cytotoxicity of compounds 6, 10, 14, 16, 17, 18, 19, and 21 was evaluated against MDA-MB-231 triple-negative breast cancer, SKBR-3 Her2-overexpressing breast cancer, and A549 lung cancer cells lines. The isolated compounds contain a hitherto undescribed modification of the terminal backbone and/or E-ring, and a possible biosynthetic pathway for their formation is proposed.

Positive Response to One-Year Treatment With Burosumab in Pediatric Patients With X-Linked Hypophosphatemia.

X-linked hypophosphatemia (XLH) causes significant burden in pediatric patients in spite of maintained treatment with phosphate supplements and vitamin D derivatives. Administration of burosumab has shown promising results in clinical trial but studies assessing its effect in the everyday practice are missing. With this aim, we analyzed the response to one-year treatment with burosumab, injected subcutaneously at 0.8 mg/kg every 2 weeks, in five children (three females) aged from 6 to 16 years, with genetically confirmed XLH. Patients were being treated with phosphate and vitamin D analogs until the beginning of burosumab treatment. In all children, burosumab administration led to normalization of serum phosphate in association with marked increase of tubular reabsorption of phosphate and reduction of elevated serum alkaline phosphatase levels. Baseline height of patients, from -3.56 to -0.46 SD, increased in the three prepubertal children (+0.84, +0.89, and +0.16 SD) during burosumab treatment. Growth improvement was associated with reduction in body mass index (-1.75, -1.47, and -0.17 SD, respectively), suggesting a salutary effect of burosumab on physical activity and body composition. Burosumab was well-tolerated, mild local pain at the injection site and transient and mild headache following the initial doses of burosumab being the only reported undesirable side effects. No patient exhibited hyperphosphatemia, progression of nephrocalcinosis, worsening of metabolic control or developed hyperparathyroidism. Mild elevation of serum PTH present at the beginning of treatment in one patient 4 was not modified by burosumab administration. These results indicate that in the clinical setting, beyond the strict conditions and follow-up of clinical trials, burosumab treatment for 1 year exerts positive effects in pediatric patients with XLH without major adverse events.

An Overview on the Properties of Ximenia Oil Used as Cosmetic in Angola.

Ximenia (Ximeniaamericana L.) is a shrub, or small tree, native from Africa and spread across different continents. In Angola, the seeds oil is used by local populations, to prevent sunburn, to smooth and hydrate the skin, and to give it a pleasant color and elasticity, to prevent stretch marks, in pregnant woman, and also as hair conditioner. Herein, an oil sold in the region (LPO), and two others extracted in laboratory, from seeds collected in the same region, were investigated in terms of their composition, chemical properties, UV transmission. The three oils are similar although the LPO is more acidic, 0.48 mg KOH/g. GC-MS analysis indicated that the major components are the fatty acids, oleic (31.82%), nervonic (11.09%), ximenic (10.22%), and hexacosa-17,20,23-trienoic acids (14.59%). Long chain fatty acids, n ≥ 20, accounted for 51.1% of the total fatty acids. A thin film of the oil showed a reduction in transmittance from 200 to 300 nm. Viscosity studies of the LPO indicated that at normal temperature of skin, the oil can be spread over the skin as a thin film. At concentrations up to 10 µg/mL, the LPO is not toxic to human keratinocytes, suggesting the safety of this oil.

Is a combined programme of manual therapy and exercise more effective than usual care in patients with non-specific chronic neck pain? A randomized controlled trial.

OBJECTIVE: The aim of this study was to compare the effectiveness of a combined intervention of manual therapy and exercise (MET) versus usual care (UC), on disability, pain intensity and global perceived recovery, in patients with non-specific chronic neck pain (CNP). DESIGN: Randomized controlled trial. SETTING: Outpatient care units. SUBJECTS: Sixty-four non-specific CNP patients were randomly allocated to MET (n = 32) or UC (n = 32) groups. INTERVENTIONS: Participants in the MET group received 12 sessions of mobilization and exercise, whereas the UC group received 15 sessions of usual care in physiotherapy. MAIN MEASURES: The primary outcome was disability (Neck Disability Index). The secondary outcomes were pain intensity (Numeric Pain Rating Scale) and global perceived recovery (Patient Global Impression Change). Patients were assessed at baseline, three weeks, six weeks (end of treatment) and at a three-month follow-up. RESULTS: Fifty-eight participants completed the study. No significant between-group difference was observed on disability and pain intensity at baseline. A significant between-group difference was observed on disability at three-week, six-week and three-month follow-up (median (P25-P75): 6 (3.25-9.81) vs. 15.5 (11.28-20.75); P < 0.001), favouring the MET group. Regarding pain intensity, a significant between-group difference was observed at six-week and three-month follow-up (median (P25-P75): 2 (1-2.51) vs. 5 (3.33-6); P < 0.001), with superiority of effect in MET group. Concerning the global perceived recovery, a significant between-group difference was observed only at the three-month follow-up (P = 0.001), favouring the MET group. CONCLUSION: This study's findings suggest that a combination of manual therapy and exercise is more effective than usual care on disability, pain intensity and global perceived recovery.

New Benzaldehyde and Benzopyran Compounds from the Endophytic Fungus Paraphaeosphaeria sp. F03 and Their Antimicrobial and Cytotoxic Activities.

Three new benzaldehyde derivatives, sporulosaldeins A - C (1: -3: ), and 3 new benzopyran derivatives, sporulosaldeins D - F (4: -6: ), were discovered from an endophytic fungus, Paraphaeosphaeria sp. F03, which was isolated from Paepalanthus planifolius leaves. Compounds 1: -6: were elucidated by 1- and 2-dimensional nuclear magnetic resonance experiments and high-resolution mass spectrometry analysis. The absolute configuration of compound 5: was determined through the comparison of experimental and calculated electronic circular dichroism data. Compounds 1: -6: were found to exhibit antifungal activity with minimum inhibitory concentration (MIC) values of 7.8 - 250 µg/mL and racemic mixture of compound 6: exhibited weak cytotoxicity against MCF-7 and LM3 with IC50 values of 34.4 and 39.2 µM, respectively.

Risk of cardiovascular involvement in pediatric patients with X-linked hypophosphatemia.

OBJECTIVE: To find out if cardiovascular alterations are present in pediatric patients with X-linked hypophosphatemia (XLH). STUDY DESIGN: Multicentre prospective clinical study on pediatric patients included in the RenalTube database ( www.renaltube.com ) with genetically confirmed diagnosis of XLH by mutations in the PHEX gene. The study's protocol consisted of biochemical work-up, 24-h ambulatory blood pressure monitoring (ABPM), carotid ultrasonography, and echocardiogram. All patients were on chronic treatment with phosphate supplements and 1-hydroxy vitamin D metabolites. RESULTS: Twenty-four patients (17 females, from 1 to 17 years of age) were studied. Serum concentrations (X ± SD) of phosphate and intact parathyroid hormone were 2.66 ± 0.60 mg/dl and 58.3 ± 26.8 pg/ml, respectively. Serum fibroblast growth factor 23 (FGF23) concentration was 278.18 ± 294.45 pg/ml (normal < 60 pg/ml). Abnormally high carotid intima media thickness was found in one patient, who was obese and hypertensive as revealed by ABPM, which disclosed arterial hypertension in two other patients. Z scores for echocardiographic interventricular septum end diastole and left ventricular posterior wall end diastole were + 0.77 ± 0.77 and + 0.94 ± 0.86, respectively. Left ventricular mass index (LVMI) was 44.93 ± 19.18 g/m2.7, and four patients, in addition to the obese one, had values greater than 51 g/m2.7, indicative of left ventricular hypertrophy. There was no correlation between these echocardiographic parameters and serum FGF23 concentrations. CONCLUSIONS: XLH pediatric patients receiving conventional treatment have echocardiographic measurements of ventricular mass within normal reference values, but above the mean, and 18% have LVMI suggestive of left ventricular hypertrophy without correlation with serum FGF23 concentrations. This might indicate an increased risk of cardiovascular involvement in XLH.

Marker of vitamin D status in healthy children: Free or total 25-hydroxyvitamin D?

OBJECTIVE: To assess if serum free 25-hydroxyvitamin D (25OHD) is a better indicator of vitamin D status than total 25OHD in healthy children. METHODS: Cross-sectional prospective clinical study was designed. We measured serum free 25OHD concentrations and its correlation with calculated free 25OHD, total 25OHD, intact parathyroid hormone (PTH), and vitamin D binding protein (DBP) in children. The influence of age, sex, ethnicity, body mass index (BMI), season of the year, diet intake, vitamin supplements, time spent outdoors and albumin concentrations on free 25OHD was also analyzed. 241 children aged from 0 days to 14 years, and living in the northern Spain (latitude 43° N), were included. RESULTS: Mean (SD) free 25OHD concentrations were 2.48 (1.39), 5.46 (3.12), 4.12 (1,72), 3.82 (1.43) pg/ml in children aged 0 days, 1 month-2 years, 2-6 years and >6 years, respectively. Correlation between directly measured and calculated free 25OHD was high and significant (r = 0.66) as well as the correlation between serum free and total 25OHD concentrations (r = 0.61). No significant correlation was found between PTH and free 25OHD (r = -0.08). The total 25OHD and PTH concentrations' correlation was inverse (r = -0.25) and significant. Neither free nor total 25OHD concentrations correlated with DBP concentrations. Among the analyzed variables, free 25OHD values were higher in spring/summer than in autumn/winter in children older than 6 years. CONCLUSIONS: : These findings do not support that free 25OHD is a better marker of vitamin D deficiency than total 25OHD in healthy pediatric population.

Portuguese recommendations for the use of biological therapies in patients with axial spondyloarthritis - 2016 update.

OBJECTIVE: To update the recommendations for the treatment of axial spondyloarthritis (axSpA) with biological therapies, endorsed by the Portuguese Society of Rheumatology. METHODS: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. At a national meeting, the 7 recommendations included in this document were discussed and updated. A draft of the full text of the recommendations was then circulated and suggestions were incorporated. A final version was again circulated before publication and the level of agreement among Portuguese Rheumatologists was anonymously assessed using an online survey. RESULTS: A consensus was achieved regarding the initiation, assessment of response and switching of biological therapies in patients with axSpA. In total, seven recommendations were produced. The first recommendation is a general statement indicating that biological therapy is not a first-line drug treatment option and should only be used after conventional treatment has failed. The second recommendation is also a general statement about the broad concept of axSpA adopted by these recommendations that includes both non-radiographic and radiographic axSpA. Recommendations 3 to 7 deal with the definition of active disease (including the recommended threshold of 2.1 for the Ankylosing Spondylitis Disease Activity Score [ASDAS] or the threshold of 4 [0-10 scale] for the Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), conventional treatment failure (nonsteroidal anti-inflammatory drugs being the first-line drug treatment), assessment of response to treatment (based on an ASDAS improvement  of at least 1.1 units or a BASDAI improvement of at least 2 units [0-10 scale] or at least 50%), and strategy in the presence of an inadequate response (where switching is recommended) or in the presence of long-term remission (where a process of biological therapy optimization can be considered, either a gradual increase in the interval between doses or a decrease of each dose of the biological therapy). CONCLUSION: These recommendations may be used for guidance in deciding which patients with axSpA should be treated with biological therapies. They cover a rapidly evolving area of therapeutic intervention. As more evidence becomes available and more biological therapies are licensed, these recommendations will have to be updated.