Management of Vertebral Fragility Fracture in Older People: Recommendations from a Spanish Consensus of Experts.

Vertebral fragility fractures (VFF) pose a challenge for appropriate care. The aim of this study was to develop consensus recommendations for the management of VFF in older people from a multidisciplinary approach. Specialists in osteoporosis belonging to different scientific societies reviewed the main clinical practice guidelines published in Spain in 2014. Thirty-five recommendations for the management of VFF were evaluated by seven experts using an anonymous survey. Consensus was defined as 80% of responses of 8 (agree) and 9 (strongly agree) on a Likert scale. Consensus was achieved in 22 recommendations (62.8%). The experts agreed on the need for anamnesis, clinical assessment, and laboratory tests, including erythrocyte sedimentation rate, proteinography, and the assessment of levels of calcium, vitamin D, alkaline phosphatase, and thyroid-stimulating hormone. Optional tests, such as bone turnover markers (BTMs), magnetic resonance imaging, bone scintigraphy, or using a fracture risk assessment tool (FRAX®), did not achieve an agreed consensus. Also, there was consensus regarding the administration of calcium/vitamin D supplements, the withdrawal of toxic habits, and personalized physical exercise. Participants agreed on the administration of teriparatide for 24 months and then a switch to denosumab or bisphosphonates in patients at high risk of fracture. Specialists in osteoporosis, primary care physicians, and geriatricians should be involved in the follow-up of patients with VFF. Although there was multidisciplinary agreement on diagnostic tests and non-pharmacological and pharmacological treatment in frail older people, therapeutic objectives should be individualized for every patient. In addition to the specific recommendations, close collaboration between the geriatrician and the primary care physician is essential for the optimal chronic management of frail patients with fragility fractures.

Bone loss induced by cancer treatments in breast and prostate cancer patients

Cancer and cancer therapies are a major factor risk for osteoporosis due to bone loss and deterioration of bone microarchitecture. Both factors contribute to a decrease in bone strength and, consequently, increased bone fragility and risk of fracture. Cancer-associated bone loss is a multifactorial process, and optimal interdisciplinary management of skeletal health, accurate assessment of bone density, and early diagnosis are essential when making decisions aimed at reducing bone loss and fracture risk in patients who have received or are receiving treatment for cancer. In this document, a multidisciplinary group of experts collected the latest evidence on the pathophysiology of osteoporosis and its prevention, diagnosis, and treatment with the support of the Spanish scientific society SEOM. The aim was to provide an up-to-date and in-depth view of osteoporotic risk and its consequences, and to present a series of recommendations aimed at optimizing the management of bone health in the context of cancer. (AU)

Correction to: Bone loss induced by cancer treatments in breast and prostate cancer patients

In the sentence beginning ‘In this document…’ in the Abstract section of this article, the text ‘In this document, a multidisciplinary group of experts collected the latest evidence on the pathophysiology of osteoporosis and its prevention, diagnosis, and treatment with the support of the Spanish scientific societies SEOM, SER, SEIOMM, and SECOT’ should have read ‘In this document, a multidisciplinary group of experts collected the latest evidence on the pathophysiology of osteoporosis and its prevention, diagnosis, and treatment with the support of the Spanish scientific society SEOM’. (AU)

Recomendaciones de práctica clínica para el diagnóstico y el tratamiento de la hipofosfatemia ligada al cromosoma X: un consenso basado en el método ADAPTE / Clinical practice recommendations for the diagnosis and treatment of X-linked hypophosphatemia: A consensus based on the ADAPTE method

Antecedentes y objetivoEl objetivo de este proyecto fue adaptar la primera guía de práctica clínica en la hipofosfatemia ligada al cromosoma X (XLH) aparecida en 2019 a nuestro medio siguiendo un proceso sistemático basado en el método ADAPTE.Materiales y métodosLa adaptación de las guías a nuestro ámbito de aplicación e implementación se llevó a cabo en 3 fases —puesta en marcha, adaptación y finalización— mediante un grupo de expertos implicados en el manejo de los pacientes con XLH.ResultadosSiguiendo la guía original, se presentan las recomendaciones acordadas por el grupo elaborador de las guías para el diagnóstico, la frecuencia y el ámbito de las visitas y el seguimiento específico en niños y adultos. Por otro lado, se establecen las recomendaciones para ambas franjas de edad con tratamiento convencional, así como con burosumab en niños o adultos y las relacionadas al controvertido uso de hormona de crecimiento en niños. También se proponen sugerencias en cuanto al seguimiento y al manejo de las alteraciones del aparato locomotor y tratamiento ortopédico en niños, la salud dental y la audición y las complicaciones neuroquirúrgicas. Por último, se plantean una serie de cuestiones y áreas en las que profundizar en una posible investigación futura.ConclusionesEstas recomendaciones constituyen la adaptación sistemática a nuestro medio de la primera guía de práctica clínica basada en la evidencia para el diagnóstico y el manejo de la XLH, y esperamos que pueda contribuir al manejo adecuado de la enfermedad. (AU)

Background and objectiveThe objective of this project was to adapt to our setting following a systematic process based on the ADAPTE method the first clinical practice guidelines on X-linked hypophosphatemia (XLH) that were published in 2019.Materials and methodsThe adaptation of the guidelines to our application and implementation setting was carried out in three phases —start-up, adaptation, and finalization— by a group of experts involved in the management of patients with XLH.ResultsFollowing the original guide, the recommendations agreed by the group that elaborated the guidelines for diagnosis, frequency and scope of visits and specific follow-up in children and adults are presented. On the other hand, recommendations are established for both age groups with conventional treatment, as well as with burosumab in children or adults and those related to the controversial use of growth hormone in children. Suggestions are also proposed regarding the monitoring and management of musculoskeletal disorders and orthopedic treatment in children, dental health and hearing, and neurosurgical complications. Finally, a series of questions and areas are raised in order to deepen the possible future investigation.ConclusionsThese recommendations constitute the systematic adaptation to our setting of the first evidence-based clinical practice guide for the diagnosis and management of XLH and we hope that they can contribute to the adequate management of the disease. (AU)

Bone loss induced by cancer treatments in breast and prostate cancer patients.

Cancer and cancer therapies are a major factor risk for osteoporosis due to bone loss and deterioration of bone microarchitecture. Both factors contribute to a decrease in bone strength and, consequently, increased bone fragility and risk of fracture. Cancer-associated bone loss is a multifactorial process, and optimal interdisciplinary management of skeletal health, accurate assessment of bone density, and early diagnosis are essential when making decisions aimed at reducing bone loss and fracture risk in patients who have received or are receiving treatment for cancer. In this document, a multidisciplinary group of experts collected the latest evidence on the pathophysiology of osteoporosis and its prevention, diagnosis, and treatment with the support of the Spanish scientific society SEOM. The aim was to provide an up-to-date and in-depth view of osteoporotic risk and its consequences, and to present a series of recommendations aimed at optimizing the management of bone health in the context of cancer.

Clinical practice recommendations for the diagnosis and treatment of X-linked hypophosphatemia: A consensus based on the ADAPTE method. / Recomendaciones de práctica clínica para el diagnóstico y el tratamiento de la hipofosfatemia ligada al cromosoma X: un consenso basado en el método ADAPTE.

BACKGROUND AND OBJECTIVE: The objective of this project was to adapt to our setting following a systematic process based on the ADAPTE method the first clinical practice guidelines on X-linked hypophosphatemia (XLH) that were published in 2019. MATERIALS AND METHODS: The adaptation of the guidelines to our application and implementation setting was carried out in three phases -start-up, adaptation, and finalization- by a group of experts involved in the management of patients with XLH. RESULTS: Following the original guide, the recommendations agreed by the group that elaborated the guidelines for diagnosis, frequency and scope of visits and specific follow-up in children and adults are presented. On the other hand, recommendations are established for both age groups with conventional treatment, as well as with burosumab in children or adults and those related to the controversial use of growth hormone in children. Suggestions are also proposed regarding the monitoring and management of musculoskeletal disorders and orthopedic treatment in children, dental health and hearing, and neurosurgical complications. Finally, a series of questions and areas are raised in order to deepen the possible future investigation. CONCLUSIONS: These recommendations constitute the systematic adaptation to our setting of the first evidence-based clinical practice guide for the diagnosis and management of XLH and we hope that they can contribute to the adequate management of the disease.

Adult height and long-term outcomes after rhIGF-1 therapy in two patients with PAPP-A2 deficiency.

PAPP-A2 deficiency is a novel syndrome characterized by short stature due to low IGF bioactivity, skeletal abnormalities and decreased bone mineral density (BMD). Treatment with recombinant human IGF-1 (rhIGF-1) for 1 year demonstrated to increase growth velocity and BMD, without reported adverse effects, but data regarding the long-term efficacy and safety of rhIGF-1 administration in this entity has not yet been reported. Two Spanish siblings with short stature due to a homozygous loss-of-function mutation in the PAPP-A2 gene (p.D643fs25*) were treated with rhIGF-1 twice daily for six years. Growth velocity continued to increase and both patients achieved their target height. Free IGF-1 concentrations increased notably after rhIGF-1 administration, with serum IGFBP-3, IGFBP-5 and ALS levels also being higher during treatment. BMD was progressively normalized and an increase in lean mass was also noted during treatment. No episodes of hypoglycemia or any other adverse effects were documented. An increase in the growth of kidney and spleen length was observed in one of the patients.

Trabecular bone score and bone mineral density in patients with long-term controlled acromegaly.

OBJECTIVE: Acromegaly is associated with increased vertebral fracture (VFs) risk not correlated to bone mineral density (BMD). Trabecular bone score (TBS), related to bone microarchitecture, provides information on bone strength. This cross-sectional study considered the usefulness of TBS and BMD to assess bone status in long-term controlled acromegalic patients. DESIGN, PATIENTS, MEASUREMENTS: 26 acromegaly patients (14 female and 12 males) were included in the study. A further 117 subjects were recruited as controls (58 females and 57 males). BMD was measured using dual-energy X-ray absorptiometry (DXA), TBS was obtained applying Medimaps software 2.0. Biochemical parameters were determined by standardized techniques. RESULTS: 73% of patients with acromegaly exhibited normal lumbar spine (LS) BMD. TBS was normal in 38% of acromegalic patients and partially degraded or degraded in 31% of patients, respectively. No differences were found in LS BMD between acromegalic patients and controls. TBS values were significantly lower in patients with acromegaly (1.27 ± 0.13 vs. 1.35 ± 0.17, p = .01). Postsurgical remission was associated with higher TBS values (1.35 ± 0.10 vs. 1.23 ± 0.13, p = .02) and pituitary radiotherapy treatment with lower TBS values (1.18 ± 0.12 vs. 1.31 ± 0.12, p = .004). On multivariate analysis, age, BMI and LS BMD were predictors of TBS changes in patients with acromegaly (p < .05). CONCLUSIONS: Patients with long-term controlled acromegaly can exhibit deterioration of bone microstructure measured with TBS, despite BMD measurement not showing bone loss. Our study suggests that TBS is useful for monitoring the bone status changes in acromegalic patients.

Identification of Compound Heterozygous Variants in LRP4 Demonstrates That a Pathogenic Variant outside the Third ß-Propeller Domain Can Cause Sclerosteosis.

Sclerosteosis is a high bone mass disorder, caused by pathogenic variants in the genes encoding sclerostin or LRP4. Both proteins form a complex that strongly inhibits canonical WNT signaling activity, a pathway of major importance in bone formation. So far, all reported disease-causing variants are located in the third ß-propeller domain of LRP4, which is essential for the interaction with sclerostin. Here, we report the identification of two compound heterozygous variants, a known p.Arg1170Gln and a novel p.Arg632His variant, in a patient with a sclerosteosis phenotype. Interestingly, the novel variant is located in the first ß-propeller domain, which is known to be indispensable for the interaction with agrin. However, using luciferase reporter assays, we demonstrated that both the p.Arg1170Gln and the p.Arg632His variant in LRP4 reduced the inhibitory capacity of sclerostin on canonical WNT signaling activity. In conclusion, this study is the first to demonstrate that a pathogenic variant in the first ß-propeller domain of LRP4 can contribute to the development of sclerosteosis, which broadens the mutational spectrum of the disorder.

Association of Low Serum 25OHD Levels with Abnormal Bone Microarchitecture in Well-Differentiated Thyroid Cancer.

The association of low levels of 25 hydroxyvitamin D (25OHD) with papillary thyroid cancer (PTC) is being studied, as to whether it is a risk factor or as a coincidental one. This study aimed to evaluate serum levels of deficiency, insufficiency, and sufficiency of 25OHD in PTC and its relationship with the trabecular bone score (TBS) and bone mineral density (BMD). This study includes 134 postmenopausal women with PTC, followed for 10 years. BMD was measured with DXA Hologic QDR 4500, and TBS with Med-Imaps iNsight2.0 Software. Mean serum 25OHD was 23.09 ± 7.9 ng/mL and deficiency, insufficiency, and sufficiency levels were 15.64 ± 2.9, 25.27 ± 2.7, and 34.7 ng/mL, respectively. Parathyroid hormone (PTH) and bone alkaline phosphatase (BAP) were higher in deficiency (57.65 ± 22.6 ng/mL; 29.5 ± 14 U/L) and in insufficiency (45.88 ± 19.8 ng/mL; 23.47 ± 8.8 U/L) compared with sufficiency of 25OHD (47.13 ± 16 and 22.14± 9.7 ng/mL) (p = 0.062 and p = 0.0440, respectively). TBS was lower in patients with 25OHD < 20 ng/mL (1.24 ± 0.13) compared with between 20-29 (1.27 ± 0.13, p < 0.05) and 30 ng/mL (1.31 ± 0.11, p < 0.01). We found low TBS in patients with PTC and long-term follow-up associated with low serum 25OHD levels, not associated with cancer stage, or accumulative iodine radioactive dose. Low 25OHD associated with deleterious bone quality in patients with PTC should be restored for the prevention of fractures.

Trabecular bone deterioration in differentiated thyroid cancer: Impact of long-term TSH suppressive therapy.

BACKGROUND: Conflicting results has been reported regard osteoporosis and fractures in patients with Differentiated Thyroid Cancer (DTC). Our objective was to evaluate the long-term effects of TSH suppression therapy with Levothyroxine (LT4) on trabecular bone score (TBS) and bone mineral density (BMD) in females with DTC after thyroidectomy. METHODS: About 145 women with resected DTC and receiving long-term TSH therapy, were stratified according to the degree of TSH suppression. Mean duration of follow-up was 12.3 ± 6.1 years. BMD and TBS, were assessed using dual-energy X-ray absorptiometry (DXA) and TBS iNsight (Med-Imaps), at baseline (1-3 months after surgery) and at the final study visit. RESULTS: In patients stratified by duration of TSH suppression therapy (Group I, 5-10 years; Group II, >10 years), slight increases from baseline TSH levels were observed. Significant decreases in LS-BMD and FN-BMD were seen in patients after >10 years. TBS values were lower in Groups I (1.289 ± 0.122) and II (1.259 ± 0.129) compared with baseline values (P = .0001, both groups). Regarding the degree of TSH suppression, TBS was significantly reduced in those with TSH < 0.1 µU/mL (P = .0086), and not in patients with TSH suppression of 0.1.-0.5 or >0.5 µU/mL. CONCLUSIONS: We found deterioration of trabecular structure in patients with DTC and TSH suppression therapy below 0.1 µU/mL and after 5-10 years of follow-up. Significant changes in BMD according to TSH levels were not observed. Trabecular Bone Score is a useful technique for identifying thyroid cancer patients with risk of bone deterioration.

Hypophosphataemic Rickets: Similar Phenotype of Different Diseases.

Hypophosphataemic rickets (HR) is a group of rare disorders caused by excessive renal phosphate wasting in which the participation of fibroblast growth factor 23 (FGF23) can be prominent. These diseases pose therapeutic challenges with important consequences for growth and bone development in childhood, with higher risk of fractures and poorer bone healing, dental problems, and nephrolithiasis or nephrocalcinosis. In some cases, the diagnostic delay can be very long; laboratory findings and an exhaustive anamnesis could help distinguish between various pathologies, and FGF23 values-although currently not routinely measured-have implications for the differential diagnosis. Genetic testing is encouraged, especially in sporadic or insidious cases. In this review we discuss the clinical features of HR, with a particular emphasis on the differential diagnosis and the therapeutic implications.

Low trabecular bone score in postmenopausal women with differentiated thyroid carcinoma after long-term TSH suppressive therapy.

The effect of thyroid suppression therapy (TST) on trabecular bone scores (TBS) and bone mineral density (BMD) in thyroidectomized women with differentiated thyroid carcinoma (DTC) on long-term follow-up is presently not conclusive. PATIENTS AND METHODS: We carried out a study in 61 premenopausal and 84 postmenopausal Caucasian women with DTC. Serum biochemistry, bone markers, TBS, BMD, and bone fractures were evaluated 1-3 months post surgery and after a median follow-up of 10 years. RESULTS: In the final study, patients belonged to Group I Premenopausal (n = 14) who remained in this status; Group II Premenopausal who became postmenopausal (n = 47); Group III patients who were and continued as postmenopausal (n = 84). Baseline premenopausal patients had a normal TBS mean value of 1.39 ± 0.14 significantly higher than that found in postmenopausal 1.31 ± 0.12 (p = 001). In the final study, premenopausal patients continued to have a normal TBS of 1.46 ± 0.08 compared to the significantly lower value of postmenopausal patients 1.25 ± 0.11 (p = 0.0009). Lumbar BMD (L-BMD) loss after the long-term study was significant in Group II (0.99 g/cm2 ± 0.13 vs. 0.91 ± 0.12 g/cm2, p < 0.0001) and there was a slight, but not significant, bone loss in Group I (1.00 ± 0.12 vs. 0.98 ± 0.11, p = 0.1936) and in Group III (0.86 ± 0.12 vs. 0.84 ± 0.15, p = 0.1924) compared with baseline values. CONCLUSION: Longer-term suppression therapy in female patients with DTC did not increase significantly the risk of bone loss, although we found in postmenopausal patients deterioration of bone microarchitecture. TBS study should be considered in the evaluation of postmenopausal DTC patients on long-term DTC for the evaluation of the risk of fractures.

Documento de consenso de osteoporosis del varón / Consensus document on osteoporosis in males

Objetivo: Proporcionar unas recomendaciones prácticas para la evaluación y tratamiento de la osteoporosis del varón. Participantes. Miembros del Grupo de Metabolismo Mineral de la Sociedad Española de Endocrinología y Nutrición. Métodos: Las recomendaciones se formularon de acuerdo con el sistema Grading of Recommendations, Assessment, Development and Evaluation (GRADE) para establecer tanto la fuerza de las recomendaciones como el grado de evidencia. Se realizó una búsqueda sistemática en Medline de la evidencia disponible sobre la osteoporosis del varón usando las siguientes palabras claves asociadas: osteoporosis, men, fractures, bone mineral density, treatment, hypogonadism y prostate cancer. Se revisaron artículos escritos en inglés y español con fecha de inclusión hasta el 30 de agosto del 2017; cada tema fue revisado por 2 personas del grupo. Tras la formulación de las recomendaciones, estas se discutieron en una reunión conjunta del grupo de trabajo. Conclusiones: El documento establece unas recomendaciones prácticas basadas en la evidencia acerca del diagnóstico, evaluación y tratamiento de la osteoporosis del varón y situaciones especiales como el hipogonadismo y el tratamiento con terapia de déficit androgénico en el carcinoma de próstata

Objective: To provide practical recommendations to assess and treat osteoporosis in males. Participants. Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology. Methods: Recommendations were formulated using the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in Medline (PubMed) using the following associated terms: «osteoporosis», «men», «fractures», «bone mineral density», «treatment», «hypogonadism», and «prostate cancer». Papers in English and Spanish with publication date before 30 August 2017 were included. Current evidence for each disease was reviewed by 2 group members. Finally, recommendations were discussed in a meeting of the working group. Conclusions: The document provides evidence-based practical recommendations for diagnosis, assessment, and management of osteoporosis in men and special situations such as hypogonadism and prostate cancer

Identificación de hipofosfatasia en la práctica clínica: manifestaciones clínicas y recomendaciones diagnósticas en pacientes adultos / Identification of hypophosphatasia in a clinical setting: Clinical manifestations and diagnostic recommendations in adult patients

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Seven years of follow up of trabecular bone score, bone mineral density, body composition and quality of life in adults with growth hormone deficiency treated with rhGH replacement in a single center.

BACKGROUND: Adult growth hormone deficiency (AGHD) is characterized by impaired physical activity, diminished quality of life (QoL), weight and fat mass gain, decreased muscle mass and decreased bone mineral density (BMD). The aim of this study was to evaluate the effects of long-term treatment (7 years) with recombinant human growth hormone (rhGH) on metabolic parameters, body composition (BC), BMD, bone microarchitecture and QoL. PATIENTS AND METHODS: In this prospective study, BMD and BC were assessed by dual-energy X-ray absorptiometry (DXA). Bone microarchitecture was assessed with the trabecular bone score (TBS). The QoL-AGHDA test was used to assess QoL. RESULTS: A total of 18 AGHD patients (mean age, 37.39 ± 12.42) were included. Body weight and body mass index (BMI) showed a significant increase after 7 years (p = 0.03 and p = 0.001, respectively). There was a significant tendency of body fat mass (BFM) (p = 0.028) and lean body mass (LBM) (p = 0.005) to increase during the 7 years of rhGH treatment. There was a significant increase in lumbar spine (LS) BMD (p = 0.01). TBS showed a nonsignificant decrease after 7 years of treatment, with a change of -0.86% ± 1.95. QoL showed a large and significant improvement (p = 0.02). CONCLUSION: Long-term rhGH treatment in AGHD patients induces a large and sustained improvement in QoL. Metabolic effects are variable with an increase in LBM as well as in BMI and BFM. There is a positive effect on BMD based on the increase in LS BMD, which stabilizes during long-term therapy and is not associated with a similar increase in bone microarchitecture.

Recalcitrant hypocalcaemia in a patient with post-thyroidectomy hypoparathyroidism and Roux-en-Y gastric bypass.

INTRODUCTION: Roux-en-Y gastric bypass (RYGB) places patients at an increased risk of hypocalcaemia due to the reduction in calcium absorption (because the procedure bypasses the duodenum and jejunum) and vitamin D deficiency. Subsequent thyroid surgery increases the risk of severe hypocalcaemia due to potential post-operative hypoparathyroidism. Only a few cases have been published before of this type of treatment-challenging hypocalcaemia. CLINICAL PRESENTATION: We report the case of a 31-year-old woman with a previous RYGB, who suffered severe and symptomatic chronic hypocalcaemia after total thyroidectomy. She required aggressive therapy with oral calcium and calcitriol and frequent calcium infusions, but there was no improvement in serum calcium level. Due to the lack of response to standard therapy, teriparatide treatment was started (first with subcutaneous injections and thereafter with a multipulse subcutaneous infusor) but the results were disappointing. As there was no response to different medical treatments, reversal of RYGB was performed with no complications and a subsequent sustained increase in serum calcium level. CONCLUSIONS: This case shows that patients with postoperative hypoparathyroidism and RYGB have increased risk of severe recalcitrant symptomatic hypocalcaemia. In our case teriparatide was ineffective but, as this is the first patient reported, more results are needed to evaluate properly the effect of teriparatide in this multifactorial hypocalcaemia. Reversal of RYGB should be considered when medical therapy has failed, because surgery restores an adequate absorption of calcium and vitamin D from previously bypassed duodenum and proximal jejunum.

Trabecular bone score in patients with liver transplants after 1 year of risedronate treatment.

The aim of this study was to analyse the effect of risedronate on Trabecular Bone Score in liver transplant patients with low bone mass, during 1-year follow-up. In this retrospective cohort study, trabecular bone score (TBS) was calculated from dual X-ray absorptiometry images of the lumbar spine (LS), collected from a prospective randomized open-label 1-year trial performed in liver recipient patients. A total of 89 patients with osteopenia or osteoporosis were randomized to receive RIS plus calcium and vitamin D3 or calcium and vitamin D3. TBS was low in both groups at baseline, 6 and 12 months. Baseline TBS at the LS showed degraded microarchitecture in 22.8% of patients, partially degraded in 40.3%, and normal values in 36.8% of the patients. After 1 year of treatment, no difference in TBS was observed between both groups. No correlations were found between bone mineral density (BMD) and TBS values at any follow-up time point. No relationship was found between BMD, TBS or immunosuppressive drugs with incidental fracture. No significant effect in TBS was observed in liver transplant patients treated with RIS or calcium and vitamin D3 after 1 year of follow-up. In these patients, the clinical usefulness of this new tool should be established.