El manejo multidisciplinar mejora el diagnóstico genético de las enfermedades renales hereditarias en la era de next generation sequencing (NGS) / Multidisciplinary management improves the genetic diagnosis of hereditary kidney diseases in the next generation sequencing (NGS) era

Antecedentes y objetivo Las enfermedades renales hereditarias (ERH) son una causa frecuente de enfermedad renal crónica, habiéndose incrementado su diagnóstico desde la introducción de la secuenciación masiva (NGS). En 2018 se fundó la Unidad multidisciplinar de Enfermedades Renales Hereditarias de la Región de Murcia basándose en el estudio genético de las ERH mediante panel de genes. El objetivo de este estudio es analizar los resultados obtenidos en los primeros tres años de funcionamiento, así como analizar los factores clínicos que se asocian a la obtención de un diagnóstico genético final. Materiales y métodos Se incluyeron los pacientes estudiados mediante panel de genes de ERH y se compararon las características entre los que obtuvieron un diagnóstico genético final y los que no. Resultados Se estudiaron un total de 360 pacientes, detectándose variantes genéticas en 164 pacientes (45,6%) no relacionados familiarmente. Cuarenta y cinco de estas variantes eran de significado clínico incierto precisando estudio de cosegregación familiar, facilitado por la unidad multidisciplinar. Globalmente, considerando los resultados obtenidos con el panel de NGS realizado en el CBGC y los estudios genómicos ampliados, se consiguió un rendimiento diagnóstico final de ERH del 33,3% (120/360), contando hallazgos incidentales, del 35,6% (128/360). Se estudiaron 223 pacientes con sospecha de síndrome de Alport, confirmándose el diagnóstico en un 28,5% (gen más frecuente COL4A4), los cuales eran con más frecuencia mujeres, y con clara historia familiar compatible. También tenían con más frecuencia microhematuria, aunque 5 pacientes sin microhematuria confirmaron diagnóstico. No hubo diferencias en la edad, proteinuria, función renal, hipoacusia o alteraciones oftalmológicas (AU)

Background and objective Hereditary kidney diseases (HKD) are a frequent cause of chronic kidney disease, and their diagnosis has increased since the introduction of next generation sequencing (NGS). In 2018, the Multidisciplinary Unit for Hereditary Kidney Diseases of the Region of Murcia (UMERH-RM) was founded based on the genetic study of HKD. The objective of this study is to analyze the results obtained in the first 3 years of operation, and to analyze the clinical factors associated to a final genetic diagnosis. Materials and methods All the patients studied with the HKD gene panel were included. The characteristics between those who obtained a final genetic diagnosis and those who did not were compared. Results A total of 360 patients were studied, detecting genetic variants in 164 not related patients (45.6%). 45 of these were variants of uncertain significance requiring a family co-segregation study, which was facilitated by the multidisciplinary unit. Overall, considering the results obtained with the NGS panel and the extended genomic studies, a final diagnostic yield of HRD of 33.3% (120/360) was achieved, and including incidental findings 35.6% (128/360). Two hundred and twenty-three patients with suspected Alport syndrome were studied. Diagnosis was confirmed in 28.5% (COL4A4 most frequent gene), more frequently women with an obvious compatible family history. They also had frequently microhematuria, although 5 patients without microhematuria confirmed the diagnosis. There were no differences in age, proteinuria, renal function, hearing loss, or ophthalmologic abnormalities. The most frequent finding in the renal biopsy was mesangial proliferation. We estimate that 39 patients avoided renal biopsy (AU)

Multidisciplinary management improves the genetic diagnosis of hereditary kidney diseases in the next generation sequencing (NGS) era.

BACKGROUND AND OBJECTIVE: Hereditary kidney diseases (HKD) are a frequent cause of chronic kidney disease, and their diagnosis has increased since the introduction of next generation sequencing (NGS). In 2018, the Multidisciplinary Unit for Hereditary Kidney Diseases of the Region of Murcia (UMERH-RM) was founded based on the genetic study of HKD. The objective of this study is to analyze the results obtained in the first 3 years of operation, and to analyze the clinical factors associated to a final genetic diagnosis. MATERIALS AND METHODS: All the patients studied with the HKD gene panel were included. The characteristics between those who obtained a final genetic diagnosis and those who did not were compared. RESULTS: A total of 360 patients were studied, detecting genetic variants in 164 not related patients (45.6%). 45 of these were variants of uncertain significance requiring a family co-segregation study, which was facilitated by the multidisciplinary unit. Overall, considering the results obtained with the NGS panel and the extended genomic studies, a final diagnostic yield of HRD of 33.3% (120/360) was achieved, and including incidental findings 35.6% (128/360). Two hundred and twenty-three patients with suspected Alport syndrome were studied. Diagnosis was confirmed in 28.5% (COL4A4 most frequent gene), more frequently women with an obvious compatible family history. They also had frequently microhematuria, although 5 patients without microhematuria confirmed the diagnosis. There were no differences in age, proteinuria, renal function, hearing loss, or ophthalmologic abnormalities. The most frequent finding in the renal biopsy was mesangial proliferation. We estimate that 39 patients avoided renal biopsy. A total of 101 patients with suspected PKD were also studied, 49.5% had a conclusive genetic result (most frequent gene PKD1), more frequently women, with larger kidney sizes (although 9 patients with normal kidney size confirmed diagnosis). Again, the most predictive characteristic of genetic outcome was family history. CONCLUSIONS: The implementation of an NGS panel for HKD, together with the multidisciplinary approach to cases, has improved the diagnostic performance of HKD. In our sample, autosomal dominant Alport syndrome is of highest incidence. Ophthalmological and auditory examinations did not contribute to the diagnosis. We have seen a significant decrease in the indication of renal biopsies thanks to molecular diagnosis. The multidisciplinary approach, with the active participation of nephrologists, paediatricians, clinical and molecular geneticists, with insistence on adequate patient phenotyping and review of their family history, offers a better interpretation of genetic variants, allowing reclassification of the diagnosis of some nephropathies, thus improving their management and genetic advice.

A multidisciplinary dermatology-gastroenterology-rheumatology (DER.RE.GA) unit for the care of patients with immune-mediated inflammatory diseases: analysis of the first 5 years from the dermatologist's perspective.

Immune-mediated inflammatory diseases (IMIDs) constitute a heterogenous group of chronic and highly disabling conditions. The clinical challenges they often pose led to formation of numerous dermo-rheumatological interdisciplinary units around the world, which are reported to benefit their patients in various ways. The present paper describes our experience with a multidisciplinary dermatology-rheumatology-gastroenterology unit DERREGA at the IRCCS Foundation Policlinico San Matteo of Pavia over a period of 5 years of its activity (2017-2022). A digital database was created, containing the medical records of 146 patients referred to the dermatology unit only by rheumatologists or gastroenterologists belonging to the multidisciplinary unit DERREGA. Then, aspects such as demographics, initial basis of referral and final diagnosis among the patients were analyzed retrospectively. Patients were classified as either gastroenterological or rheumatological, and then categorized according to the specific basis of referral. Most of the gastroenterological patients (97%) were affected by inflammatory bowel diseases (IBDs). Rheumatological patients were divided in three subgroups, including patients referred with vasculitis, arthropathies (undifferentiated arthritis, psoriatic arthritis and other arthritis) and other rheumatological diseases. Then, final diagnoses were evaluated in each group. Almost a third of IBD patients received a diagnosis of paradoxical psoriasis. Dermatological examination allowed diagnosis of minimal psoriasis based on Caspar criteria in over 70% of the patients admitted with undifferentiated arthritis. A multidisciplinary approach is suggested to provide more effective management of IMIDs and, specifically, from a dermatological perspective, allows for the diagnosis of minimal manifestations of psoriasis in patients with a provisional diagnosis of undifferentiated arthritis.

Clinical-epidemiological profile of the patient attended in a fracture liaison service (FLS) of a regional hospital in north-west of Spain. / [Artículo traducido] Perfil clínico-epidemiológico del paciente atendido en una unidad multidisciplinar de fractura de cadera de un hospital de primer nivel en el noroeste de España.

INTRODUCTION: Hip fractures constitute a capital public health issue associated with aging and frailty because of its impact on both quality of life and morbidity and mortality in older people. Fracture liaison services (FLS) have been proposed as tools to minimize this emergent problem. MATERIAL AND METHODS: A prospective observational study was conducted with 101 patients treated for hip fracture by the FLS of a regional hospital between October 2019 and June 2021 (20 months). Epidemiological, clinical, surgical, and management variables were collected during admission and up to 30 days after discharge. RESULTS: Mean age of patients was 87.6 ± 6.1 years and 77.2% were female. Some degree of cognitive impairment was detected at admission in 71.3% of patients using the Pfeiffer questionnaire, and 13.9% were nursing home residents, and 76.24% could walk independently before the fracture. Fractures were more commonly pertrochanteric (45.5%). Patients were receiving antiosteoporotic therapy in 10.9% of cases. The median surgical delay from admission was 26 h (RIC 15-46 h), the median length of stay was 6 days (RIC 3-9 days) and in-hospital mortality was 10.9%, and 19.8% at 30 days, with a readmission rate of 5%. DISCUSSION: Patients treated in our FLS at the beginning of its activity were similar to the general picture in our country in terms of age, sex, type of fracture, and proportion of patients treated surgically. A high mortality rate was observed, and low rates of pharmacological secondary prevention were followed at discharge. Clinical results of FLS implementation in regional hospitals should be assessed prospectively in order to decide their suitability.

Uso de NT-proBNP en el seguimiento ambulatorio de pacientes con insuficiencia cardiaca con fracción de eyección del ventrículo izquierdo reducida en una unidad multidisciplinaria de insuficiencia cardiaca

Introducción: La insuficiencia cardíaca (IC) es un síndrome clínico prevalente a nivel mundial, que se beneficia del abordaje multidisciplinario, pero su seguimiento ambulatorio sigue siendo un reto. La utilidad diagnóstica y pronóstica del NT-proBNP está apoyada en la evidencia actual; pero su uso en el seguimiento aún no ha sido definido. En el presente estudio se busca determinar si la variación en el tiempo del valor de NT-proBNP se relacionó con modificación en el tratamiento farmacológico de pacientes ambulatorios con IC y fracción de eyección del ventrículo izquierdo reducida (FEVI ≤ 40%) de una unidad multidisciplinaria de insuficiencia cardíaca (UMIC). Metodología: Estudio cohorte retrospectivo, de pacientes que cumplieron con los criterios de inclusión: 2 o más cuantificaciones de NT-proBNP en 12 meses y un seguimiento mínimo de 2 años entre los años 2013 y 2017. Resultados: De un total de 566 sujetos integrantes de cohorte activa de UMIC se incluyeron 107 que cumplieron criterios de inclusión; la mayoría hombres (58%), edad mediana de 63 años (Q1;Q3: 55,9;71,2 años), la principal comorbilidad fue hipertensión arterial (71%). En 56% de la población la etiología de IC fue no isquémica y el 50% tenía una clase funcional - NYHA I. La mediana de NT-proBNP basal fue de 698 pg/ml (Q1;Q3: (218;1564 pg/ml), con FEVI basal mediana de 30% (Q1;Q3: 27%;40%). En 55% de los pacientes la variación del valor de NT-proBNP durante el seguimiento se relacionó con modificaciones en el tratamiento farmacológico. Conclusiones: En la mitad de la población de nuestra cohorte se evidenció que los valores de NT-proBNP se relacionaron con cambios en el tratamiento farmacológico, independientemente de la situación clínica.

Introduction: Heart failure (HF) is a prevalent clinical syndrome worldwide, which benefits from a multidisciplinary approach, but its outpatient follow-up remains a challenge. The diagnostic and prognostic utility of NT-proBNP is supported by current evidence, but its use in monitoring has not yet been defined. The present study sought to determine whether the variation over time in the value of NT-proBNP was related to changes in the pharmacological treatment of outpatients with HF and reduced left ventricular ejection fraction (LVEF ≤ 40%) in a multidisciplinary heart failure unit. (MHFU). Methodology: Retrospective cohort study of patients, who met the inclusion criteria: 2 or more quantifications of NT-proBNP in 12 months and a minimum follow-up of 2 years between 2013 and 2017. Results: Of 566 members of the MHFU active cohort, 107 met the inclusion criteria; most men (58%), median age 63 years (Q1;Q3: 55.9;71.2), the main comorbidity was arterial hypertension (71%). The etiology of HF was non-ischemic in 56% of the population, and 50% had a functional class - NYHA I. Median baseline NT-proBNP was 698 pg/ml (Q1;Q3: (218;1564), with median baseline LVEF of 30% (Q1;Q3: 27;40). In 55% of the patients, the variation in the NT-proBNP value during follow-up was related to changes in pharmacological treatment. Conclusions: In half of the population of our cohort, it was shown that NT-proBNP values were related to changes in pharmacological treatment, regardless of the clinical situation.

Introdução: A insuficiência cardíaca (IC) é uma síndrome clínica prevalente em todo o mundo, que se beneficia de uma abordagem multidisciplinar, mas seu acompanhamento ambulatorial continua sendo um desafio. A utilidade diagnóstica e prognóstica do NT-proBNP é suportada pelas evidências atuais, mas seu uso no monitoramento ainda não foi definido. O presente estudo procurou determinar se a variação ao longo do tempo no valor do NT-proBNP estava relacionada a mudanças no tratamento farmacológico de pacientes ambulatoriais com IC e fração de ejeção do ventrículo esquerdo (FEVE ≤ 40%) reduzida em uma unidade multidisciplinar de insuficiência cardíaca. (UMIC). Metodologia: Estudo de coorte retrospectivo de pacientes que preencheram os critérios de inclusão: 2 ou mais quantificações de NT-proBNP em 12 meses e seguimento mínimo de 2 anos entre 2013 e 2017. Resultados: Dos 566 membros da coorte ativa do UMIC, 107 preencheram os critérios de inclusão; maioria dos homens (58%), idade mediana 63 anos (Q1;Q3: 55,9;71,2), a principal comorbidade foi hipertensão arterial (71%). A etiologia da IC foi não-isquêmica em 56% da população, e 50% tinham classe funcional - NYHA I. A mediana basal do NT-proBNP foi de 698 pg/ml (Q1;Q3: (218;1564), com mediana basal FEVE de 30% (Q1;Q3: 27;40). Em 55% dos pacientes, a variação do valor de NT-proBNP durante o seguimento esteve relacionada a mudanças no tratamento farmacológico. Conclusões: Em metade da população do nosso coorte, foi demonstrado que os valores de NT-proBNP estavam relacionados a mudanças no tratamento farmacológico, independentemente da situação clínica.

Unidad multidisciplinar especializada en el tratamiento del pie diabético: evaluación y resultados / Multidisciplinary unit specialized in the treatment of diabetic foot: Evaluation and results

Introducción: En este estudio se realiza la evaluación del proceso asistencial del pie diabético tras la implantación de una vía clínica intrahospitalaria y una consulta multidisciplinar. Objetivos: Evaluar la influencia en factores relacionados con la asistencia, amputaciones y rehabilitación del paciente amputado. Metodología: Estudio retrospectivo en el que se realiza la comparación de tres períodos. Primero (3años): antes de la implantación de la vía. Segundo (5años): posterior a la implantación de la vía. Tercero (10años): posterior a la implantación de la consulta. Resultados: Una consulta especializada en la atención del pie diabético contribuye a una reducción de las amputaciones femorales y menores. Se han optimizado la valoración y el tratamiento por parte de rehabilitación de los pacientes sometidos a amputación mayor. Conclusión: La implantación de vía y consulta contribuye a aumentar la preservación del miembro inferior. Sin embargo, la incidencia sigue siendo alta, sugiriendo que los cuidados del pie diabético permanecen subóptimos.(AU)

Introduction: In this study the evaluation of the care process of the diabetic foot will be carried out after the implementation of an intra-hospital clinical pathway and a multidisciplinary consultation. Objectives: Evaluate the influence on factors related to the care, amputations, and rehabilitation of the amputee patient. Methodology: Retrospective study, in which the comparison of three periods has been made. First (3years): Before the implantation of the pathway. Second (5years): After the implementation of the pathway. Third (10years): After the implementation of the consultation. Results: A specialized consultation in diabetic foot care contributes to a reduction in femoral and minor amputations. The assessment and treatment by rehabilitation of patients undergoing major amputation has been optimized. Conclusion: The implantation of the pathway and consultation contributes to the preservation of the lower limb. However, the incidence remains high, suggesting that diabetic foot care remains suboptimal.(AU)

[Multidisciplinary unit specialized in the treatment of diabetic foot: Evaluation and results]. / Unidad multidisciplinar especializada en el tratamiento del pie diabético: evaluación y resultados.

INTRODUCTION: In this study the evaluation of the care process of the diabetic foot will be carried out after the implementation of an intra-hospital clinical pathway and a multidisciplinary consultation. OBJECTIVES: Evaluate the influence on factors related to the care, amputations, and rehabilitation of the amputee patient. METHODOLOGY: Retrospective study, in which the comparison of three periods has been made. First (3years): Before the implantation of the pathway. Second (5years): After the implementation of the pathway. Third (10years): After the implementation of the consultation. RESULTS: A specialized consultation in diabetic foot care contributes to a reduction in femoral and minor amputations. The assessment and treatment by rehabilitation of patients undergoing major amputation has been optimized. CONCLUSION: The implantation of the pathway and consultation contributes to the preservation of the lower limb. However, the incidence remains high, suggesting that diabetic foot care remains suboptimal.

Clinical, genetic and quality-of-life study of a cohort of adult patients with tuberous sclerosis.

BACKGROUND AND OBJECTIVE: Tuberous sclerosis (TS) is a condition whose manifestations in childhood have been extensively described, but whose presentation in adults is less well known. This study describes the clinical and genetic characteristics, therapeutic management and quality of life of a cohort of adult patients with TS. A comparative study of the characteristics of patients diagnosed in childhood and adulthood is also carried out. MATERIAL AND METHODS: This observational, retrospective, cross-sectional study included a large cohort of adult patients (≥ 16 years old) followed for 5 years in a specific rare diseases unit. RESULTS: Fifty-seven patients with a diagnosis of tuberous sclerosis were included, more than 50% of whom were diagnosed as adults. The mean age of the patients was 42 years (20-86). The central nervous system was the main area affected (97%), followed by the skin (80.7%) and kidneys (73%). The most frequent genetic alteration was a mutation in the TSC2 gene (47.7%). Among patients diagnosed in adulthood, there was less neurological involvement, with less frequency of epileptic seizures (30.8% vs 60.79% of patients diagnosed in childhood) and astrocytomas (3.8% vs 53.6%), less intellectual disability (11.5% vs 71.4%) and less expressiveness of the condition. 42% of patients were treated with mTOR pathway inhibitors, and presence of an angiomyolipoma was the main indication. In a quality-of-life analysis, the means of the summary indices were below the scores of the average Spanish population: (47.42 (SD ± 9.82) on the physical health scale, 45.61 (SD ± 7.99) on the mental health scale) versus 50 (SD ± 10) for the general population. CONCLUSIONS: Up to 50% of adult patients with TS were diagnosed in adulthood, and the condition is less severe with less frequent epileptic seizures and intellectual disability. 42% require treatment with mTOR inhibitors, in most cases due to the presence of AMLs. The quality of life of adult patients with TS is diminished compared to the general population.

National digestive disease specialists survey on cardiovascular risk management in non-alcoholic fatty liver disease in spanish hospitals.

BACKGROUND & AIMS: Cardiovascular disease (CVD) is the main cause of mortality among non-alcoholic fatty liver disease (NAFLD) patients. The aim was to explore the level of knowledge and clinical management of cardiovascular risk (CVR) in NAFLD patients by Digestive Disease specialists. METHODS: An anonymous web-based survey was designed with 44 close-ended questions, divided into five sections, that were based on current guidelines on CVD prevention. Between November 2019 and January 2020, Digestive Disease specialists from Spanish hospitals were invited to participate in this survey via email and Twitter. Student's t, chi-square and Fishers' exact tests, and logistic regression were used for data analysis. RESULTS: 208 clinicians completed the survey. Most respondents (83.2%) believe that NAFLD is an independent risk factor for CVD, especially in the presence of NASH and fibrosis. Personal history of CVDs and cardiovascular risk-related comorbidities are collected by more than 75% of respondents. However, less than 17% perform an elementary physical examination to address the CVR, except weight which is evaluated by 69.8%. Over 54% of respondents do not perform or request any supplementary tests for CVR assessment, and only 10.2% use specific calculators. Furthermore, 54.3% spend less than 5 minutes giving lifestyle advice, and more than 52% do not start drug treatment after a recent diagnosis of any cardiovascular comorbidity. Only 25.6% have a multidisciplinary Unit for metabolic comorbidities in their hospitals, although 89% of the respondents would support the implementation of this Unit. CONCLUSIONS: Cardiovascular risk management in daily clinical practice by Digestive Disease specialists in Spain remains suboptimal.

Profile of patients with uveitis referred to a multidisciplinary unit in northern Spain. / Caracterización de los pacientes con uveítis remitidos a una unidad multidisciplinar de referencia en el norte de España.

OBJECTIVE: To describe the main characteristics of a cohort of patients with uveitis referred to a multidisciplinary unit in northern Spain. MATERIAL AND METHODS: Retrospective analysis of clinical records of patients evaluated in the Multidisciplinary Unit of the Navarra Hospital Complex from the period January 2010 until March 2015. An analysis was performed on the demographic characteristics, origin, types of uveitis, laterality, and aetiology. The present series was also compared with 2 previous series from Castilla y León and Barcelona. RESULTS: A total of 500 patients were identified, with a mean age of 47.9±16.4 years, with 50% women. The most frequent type of uveitis was anterior uveitis (65.4%), followed by posterior uveitis (17.6%), panuveitis (15.2%), and intermediate uveitis (1.8%). The origin was unclassifiable in 31.2%, followed by non-infectious systemic disease in 29.2%. Ankylosing spondylitis was the most frequent cause in 10.8% of patients, followed by herpes infection in 9.2%, and toxoplasmosis in 7.8%, respectively. Compared with the 2other cohorts, the present cohort showed a higher proportion of unilateral anterior uveitis. Furthermore, the patients from the Navarra series had a higher prevalence of unilateral and idiopathic uveitis compared to the series from Barcelona. CONCLUSIONS: The main characteristics of the present cohort of patients with uveitis are similar to those of patients from other regions of our country. Unilateral anterior uveitis and idiopathic uveitis were the most frequent in our series.