Estimating dyskinesia severity in Parkinson's disease by using a waist-worn sensor: concurrent validity study.

Our research team previously developed an accelerometry-based device, which can be worn on the waist during daily life activities and detects the occurrence of dyskinesia in patients with Parkinson's disease. The goal of this study was to analyze the magnitude of correlation between the numeric output of the device algorithm and the results of the Unified Dyskinesia Rating Scale (UDysRS), administered by a physician. In this study, 13 Parkinson's patients, who were symptomatic with dyskinesias, were monitored with the device at home, for an average period of 30 minutes, while performing normal daily life activities. Each patient's activity was simultaneously video-recorded. A physician was in charge of reviewing the recorded videos and determining the severity of dyskinesia through the UDysRS for every patient. The sensor device yielded only one value for dyskinesia severity, which was calculated by averaging the recorded device readings. Correlation between the results of physician's assessment and the sensor output was analyzed with the Spearman's correlation coefficient. The correlation coefficient between the sensor output and UDysRS result was 0.70 (CI 95%: 0.33-0.88; p = 0.01). Since the sensor was located on the waist, the correlation between the sensor output and the results of the trunk and legs scale sub-items was calculated: 0.91 (CI 95% 0.76-0.97: p < 0.001). The conclusion is that the magnitude of dyskinesia, as measured by the tested device, presented good correlation with that observed by a physician.

Expanding the clinical features of autoinflammation and phospholipase Cγ2-associated antibody deficiency and immune dysregulation by description of a novel patient.

BACKGROUND: Autoinflammation and phospholipase Cγ2-associated antibody deficiency and immune dysregulation (APLAID) is an exceedingly rare monogenic autoinflammatory disease. To date, only five cases have been reported with four distinct pathogenic mutations. OBJECTIVES: We present a novel case of APLAID, corroborated by molecular analysis, with newly described clinical findings including central nervous system vasculitis (CNSV); and distinctive histopathological characteristics that may expand our knowledge of this rare disease's phenotype. METHODS: This is a case report presentation of a 3-year-old boy, seen at a reference paediatric hospital in Mexico. His parents authorized the use of his clinical information and photographs. RESULTS: A 3-day-old boy presented to the emergency department with a vesiculo-pustular rash that resolved within 1 week. Two months later, he developed widespread papules and pseudovesicles that evolved into infiltrated plaques. He also had periodical flares of conjunctivitis, diarrhoea and erythematous blistering acral plaques triggered by upper respiratory infections. By the age of 10 months, he experienced seizures and CNSV. Laboratory work-up showed mild neutropenia, decreased serum levels of immunoglobulins and B-cell lymphopenia. A skin biopsy revealed a dense, perivascular and interstitial histiocytic and granulomatous infiltrate, with palisading granulomas, and leucocytoclastic vasculitis with karyorrhexis. APLAID syndrome was confirmed by Sanger sequencing of PLCG2 gene [heterozygous genotype LRG_376t1:c.2543T>C or p.(Leu848Pro)]. CONCLUSIONS: Presence of CNSV has not been previously described in APLAID, however as the number of reported patients with APLAID is very small, it is possible that the overall spectrum of clinical manifestations has not been completely elucidated. The herein identified p.(Leu848Pro) variant was also documented in a Portuguese patient, suggesting that it could be a PLCG2 gene 'hot-spot'.

Corrigendum: Analysis of Correlation between an Accelerometer-Based Algorithm for Detecting Parkinsonian Gait and UPDRS Subscales.

[This corrects the article on p. 431 in vol. 8, PMID: 28919877.].

Analysis of Correlation between an Accelerometer-Based Algorithm for Detecting Parkinsonian Gait and UPDRS Subscales.

BACKGROUND: Our group earlier developed a small monitoring device, which uses accelerometer measurements to accurately detect motor fluctuations in patients with Parkinson's (On and Off state) based on an algorithm that characterizes gait through the frequency content of strides. To further validate the algorithm, we studied the correlation of its outputs with the motor section of the Unified Parkinson's Disease Rating Scale part-III (UPDRS-III). METHOD: Seventy-five patients suffering from Parkinson's disease were asked to walk both in the Off and the On state while wearing the inertial sensor on the waist. Additionally, all patients were administered the motor section of the UPDRS in both motor phases. Tests were conducted at the patient's home. Convergence between the algorithm and the scale was evaluated by using the Spearman's correlation coefficient. RESULTS: Correlation with the UPDRS-III was moderate (rho -0.56; p < 0.001). Correlation between the algorithm outputs and the gait item in the UPDRS-III was good (rho -0.73; p < 0.001). The factorial analysis of the UPDRS-III has repeatedly shown that several of its items can be clustered under the so-called Factor 1: "axial function, balance, and gait." The correlation between the algorithm outputs and this factor of the UPDRS-III was -0.67 (p < 0.01). CONCLUSION: The correlation achieved by the algorithm with the UPDRS-III scale suggests that this algorithm might be a useful tool for monitoring patients with Parkinson's disease and motor fluctuations.

Estimating bradykinesia severity in Parkinson's disease by analysing gait through a waist-worn sensor.

Bradykinesia is a cardinal symptom of Parkinson's disease (PD) and describes the slowness of movement revealed in patients. Current PD therapies are based on dopamine replacement, and given that bradykinesia is the symptom that best correlates with the dopaminergic deficiency, the knowledge of its fluctuations may be useful in the diagnosis, treatment and better understanding of the disease progression. This paper evaluates a machine learning method that analyses the signals provided by a triaxial accelerometer placed on the waist of PD patients in order to automatically assess bradykinetic gait unobtrusively. This method employs Support Vector Machines to determine those parts of the signals corresponding to gait. The frequency content of strides is then used to determine bradykinetic walking bouts and to estimate bradykinesia severity based on an epsilon-Support Vector Regression model. The method is validated in 12 PD patients, which leads to two main conclusions. Firstly, the frequency content of the strides allows for the dichotomic detection of bradykinesia with an accuracy higher than 90%. This process requires the use of a patient-dependant threshold that is estimated based on a leave-one-patient-out regression model. Secondly, bradykinesia severity measured through UPDRS scores is approximated by means of a regression model with errors below 10%. Although the method has to be further validated in more patients, results obtained suggest that the presented approach can be successfully used to rate bradykinesia in the daily life of PD patients unobtrusively.

Manifestaciones neurológicas en la enfermedad de Erdheim-Chester: a propósito de 2 casos / Neurological manifestations in Erdheim-Chester disease: Two case reports

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A double closed loop to enhance the quality of life of Parkinson's Disease patients: REMPARK system.

This paper presents REMPARK system, a novel approach to deal with Parkinson's Disease (PD). REMPARK system comprises two closed loops of actuation onto PD. The first loop consists in a wearable system that, based on a belt-worn movement sensor, detects movement alterations that activate an auditory cueing system controlled by a smartphone in order to improve patient's gait. The belt-worn sensor analyzes patient's movement through real-time learning algorithms that were developed on the basis of a database previously collected from 93 PD patients. The second loop consists in disease management based on the data collected during long periods and that enables neurologists to tailor medication of their PD patients and follow the disease evolution. REMPARK system is going to be tested in 40 PD patients in Spain, Ireland, Italy and Israel. This paper describes the approach followed to obtain this system, its components, functionalities and trials in which the system will be validated.

Type I leucocyte adhesion deficiency (LAD I). Report of a case

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Neutropenia congénita grave: análisis de las características clínicas, estudios diagnósticos, tratamiento y seguimiento a largo plazo / Severe congenital neutropenia: analysis of clinical features, diagnostic methods, treatment and long-term outcome

Introducción: La NCG es una entidad heterogénea que se manifiesta en edades precoces de la vida y se caracteriza por un fallo primario en la mielopoyesis con un RAN < 0,5 x 109/l, infecciones graves y riesgo de transformación leucémica. Objetivo: Conocer el curso evolutivo a largo plazo de los pacientes diagnosticados de NCG. Material y métodos: Se analizaron las características clínicas, los métodos diagnósticos, el tratamiento y la evolución de 11 pacientes afectados de NCG. Resultados: La mediana de edad al diagnóstico fue de 4 meses (rango: 3 días-12 años). Clínica inicial en todos los casos: infección grave. Mediana de RAN al diagnóstico: 0,2 x 109/l (rango: 0-0,37). El aspirado de médula ósea mostró en todos los casos stop madurativo a nivel de promielocito. El estudio genético mostró en 3 mutaciones, 2 que afectaban al gen ELA2 y una en el gen G6PC3. El G-CSF fue el tratamiento de elección en 9 pacientes. Seis presentaron una buena respuesta a las dosis de entre 5-15 μg/kg/día administrado de 3 a 7días por semana. Tres no respondieron a G-CSF, indicándose un TPH alogénico. En 2 pacientes el TPH fue el tratamiento de primera elección. Mediana de seguimiento de 5 años (rango: 1-10), con una supervivencia del 100% sin ningún caso de transformación leucémica. Conclusiones: A la vista de los datos podemos concluir que el estudio genético de la NCG es útil para establecer una correlación entre genotipo y fenotipo. El tratamiento de elección es la administración G-CSF por vía subcutánea, al que responden las dos terceras partes de los pacientes, indicándose el TPH para los casos de mala respuesta o en aquellos que evolucionan a SMD o leucemia, por lo que el seguimiento de esta entidad es fundamental (AU)

Introduction: Severe congenital neutropenia (SCN), a heterogeneous condition with onset at early ages, is characterised by primary myelopoiesis failure with an absolute neutrophil count (ANC) < 0.5 x109/L, severe infections and risk of leukaemic transformation. Objective: The aim of the study was to ascertain the long term outcome of patients with SCN. Material and methods: The clinical features, diagnostic methods, treatment and outcome of 11 patients with SCN were analysed. Results: The median age at diagnosis was 4 months (range: 3 days-12 years). The primary clinical manifestation was severe infection. Median ANC at diagnosis: 0.2 x 109/L (range: 0-0.37). Bone marrow aspirate showed maturation arrest at promyelocyte stage in all cases. Genetic studies revealed 3 mutations, two in ELA-2 gene and 1 in G6PC3 gene, showing a correlation between genotype and phenotype. Granulocyte Colony Stimulating Factor (G-CSF) was the first-line treatment in 9 patients; six of whom showed a good response at doses between 5 and 15 μg/kg/day for 3-7 days/week. The remaining 3 patients failed to respond to G-CSF and allogeneic stem cell transplantation (SCT) was indicated. Furthermore, SCT was the treatment of choice in two cases. Median follow-up of the cohort was 5 years (range: 1-10 years) with 100% survival and no cases of leukaemic transformation. Conclusions: We conclude that genetic study is useful for establishing a correlation between genotype and phenotype. The treatment of choice for SCN is G-CSF to which 2/3 of patients should respond; while SCT is reserved for cases of poor response or those evolving to myelodysplastic syndrome (MDS) or leukaemia; thus close follow-up of this condition is essential (AU)

[Severe congenital neutropenia: analysis of clinical features, diagnostic methods, treatment and long-term outcome]. / Neutropenia congénita grave: análisis de las características clínicas, estudios diagnósticos, tratamiento y seguimiento a largo plazo.

INTRODUCTION: Severe congenital neutropenia (SCN), a heterogeneous condition with onset at early ages, is characterised by primary myelopoiesis failure with an absolute neutrophil count (ANC) < 0.5 x10(9)/L, severe infections and risk of leukaemic transformation. OBJECTIVE: The aim of the study was to ascertain the long term outcome of patients with SCN. MATERIAL AND METHODS: The clinical features, diagnostic methods, treatment and outcome of 11 patients with SCN were analysed. RESULTS: The median age at diagnosis was 4 months (range: 3 days-12 years). The primary clinical manifestation was severe infection. Median ANC at diagnosis: 0.2 x 10(9)/L (range: 0-0.37). Bone marrow aspirate showed maturation arrest at promyelocyte stage in all cases. Genetic studies revealed 3 mutations, two in ELA-2 gene and 1 in G6PC3 gene, showing a correlation between genotype and phenotype. Granulocyte Colony Stimulating Factor (G-CSF) was the first-line treatment in 9 patients; six of whom showed a good response at doses between 5 and 15 µg/kg/day for 3-7 days/week. The remaining 3 patients failed to respond to G-CSF and allogeneic stem cell transplantation (SCT) was indicated. Furthermore, SCT was the treatment of choice in two cases. Median follow-up of the cohort was 5 years (range: 1-10 years) with 100% survival and no cases of leukaemic transformation. CONCLUSIONS: We conclude that genetic study is useful for establishing a correlation between genotype and phenotype. The treatment of choice for SCN is G-CSF to which 2/3 of patients should respond; while SCT is reserved for cases of poor response or those evolving to myelodysplastic syndrome (MDS) or leukaemia; thus close follow-up of this condition is essential.

Documento de Consenso de la Sociedad de Infectología Pediatrica y la Sociedad de Reumatología Pediatrica sobre el diagnóstico diferencial y el abordaje terapéutico de la fiebre recurrente / Consensus Document on the differential diagnosis and therapeutic approach to recurrent fever by the Paediatric Infectology Society and the Paediatric Rheumatology Society

La fiebre recurrente es un problema relativamente frecuente en la infancia. En la mayoría de las ocasiones es sencillo establecer su etiología generalmente asociada a episodios infecciosos banales. No obstante, en un pequeño porcentaje de casos estos episodios se deben a procesos de causa no infecciosa a menudo de complejo diagnóstico. En este documento se analiza el diagnóstico diferencial de la fiebre recurrente o periódica frente a otros procesos, con especial atención a las enfermedades autoinflamatorias (EA). Las EA son alteraciones de la inmunidad innata recientemente incluidas dentro de las inmunodeficiencias, sin embargo no se caracterizan por presentar infecciones lo que las diferencia de las inmunodeficiencias clásicas. Un importante número de las EA tienen una base genética conocida. La sintomatología que ocasionan se deriva de una inflamación sistémica que puede dar clínica y procesos muy variados. Uno de los grupos mejor conocidos es el formado por los síndromes hereditarios de fiebre periódica. Este grupo se caracteriza por presentar fiebre recurrente, asociada a diversos síntomas, con una relativa periodicidad y con intervalos libres o casi libres de síntomas. Para algunas de las entidades más frecuentes se dispone de criterios diagnósticos que son aquí recogidos, así como las características que deben hacernos iniciar el estudio genético. El tratamiento debe ser individualizado dada la complejidad de estos cuadros si bien se pueden dar algunas recomendaciones generales (AU)

Recurrent fever is a relatively common problem during childhood. Diagnosis is often easy and related to mild viral infections. However a small proportion of these cases originate from an underlying non-infectious process that is generally difficult to diagnose. In this paper we describe the differential diagnosis of recurrent or periodic fever versus other processes, with especial attention to autoinflammatory disorders (AD). AD are alterations of innate immunity, and they have been recently classified as an immunodeficiency. Anyhow, since infections are not present, these processes are different to the classic primary immunodeficiency. An important part of AD is of known genetic aetiology. The symptoms originate from an underlying inflammatory process and can have different clinical expressions. One of the most relevant groups is the hereditary syndromes of periodic fever. This group of diseases associates recurrent fever and several clinical symptoms with a relative periodicity, separated by intervals free or almost free of symptoms. We include the diagnostic criteria for some processes as well as the characteristics that should, eventually, lead to a genetic study. Although treatment should be individualised, we also include some general recommendations (AU)

[Consensus Document on the differential diagnosis and therapeutic approach to recurrent fever by the Paediatric Infectology Society and the Paediatric Rheumatology Society]. / Documento de Consenso de la Sociedad de Infectología Pediatrica y la Sociedad de Reumatología Pediatrica sobre el diagnóstico diferencial y el abordaje terapéutico de la fiebre recurrente.

Recurrent fever is a relatively common problem during childhood. Diagnosis is often easy and related to mild viral infections. However a small proportion of these cases originate from an underlying non-infectious process that is generally difficult to diagnose. In this paper we describe the differential diagnosis of recurrent or periodic fever versus other processes, with especial attention to autoinflammatory disorders (AD). AD are alterations of innate immunity, and they have been recently classified as an immunodeficiency. Anyhow, since infections are not present, these processes are different to the classic primary immunodeficiency. An important part of AD is of known genetic aetiology. The symptoms originate from an underlying inflammatory process and can have different clinical expressions. One of the most relevant groups is the hereditary syndromes of periodic fever. This group of diseases associates recurrent fever and several clinical symptoms with a relative periodicity, separated by intervals free or almost free of symptoms. We include the diagnostic criteria for some processes as well as the characteristics that should, eventually, lead to a genetic study. Although treatment should be individualised, we also include some general recommendations.

Simulated geochemical weathering of a mineral ash-rich biochar in a modified Soxhlet reactor.

Although there are many studies on the characterization of C in biochar and its C sequestration potential, there is little knowledge on the mineral fraction in biochar and its weathering. The latter, however, can have powerful implications on nutrient availability. In the present study, a modified Soxhlet reactor was used to simulate the long-term geochemical weathering of an ash-rich biochar produced from sewage sludge of a non-industrial area in New Zealand. The weathering process took place during a period of 300 h, with and without the addition of humic acid (1.00 g added to 20.00 g of biochar), and the treatments were referred to as treatment BC-HA and BC-B, respectively. Both the leaching kinetics and the transformations within the solid phase were studied. The results revealed that substantial amounts of K (8.5-10.2%) and S (20.2-28.3%) were recovered in the weathering solutions. Noticeable Ca (17.9-20.7%) and P (15.4%) in the solid were released but only a few were recovered in the weathering solutions because of the precipitation. The presence of humic acids increased this dissolution and thus the availability of K, S, Ca, Mg and P, but induced N immobilization. Nitrogen availability was already very low (<1.0% of the total N) due to the probable recalcitrant heterocyclic N structure. The pH of the biochar samples dropped from 8.4 to 7.5; this was mainly attributed to loss of base cations through leaching and probable carbonation of the system. The XPS spectra evidenced the oxidation of C in biochar during the weathering process with the formation of carbonyl and carboxylic functional groups. The results obtained in this study showed some promise for the positive use of modified Soxhlet extractor in simulating the geochemical weathering in ash-rich biochars and providing a better understanding on the kinetics of nutrient release. This will be key information in assessing the added value of biochars as soil amendments.

Possible association between NOD2 variants and joint surgery in psoriatic arthritis.

BACKGROUND: Psoriatic arthritis (PsA) has been inconsistently associated with common NOD2 gene variants, although some of these studies did not include patient stratification by clinical phenotype. OBJECTIVES: To analyse the association between the three common NOD2 variants (R702W, G908R and L1007fs) and clinical phenotypes of PsA, particularly with surrogate markers of severe joint destruction. PATIENTS AND METHODS: A total of 183 unrelated PsA patients and 187 controls were included. Demographic, clinical, biological and immunological characteristics were collected. Genotypes for the three common NOD2 gene variants were obtained by PCR and direct sequencing. RESULTS: NOD2 variants in PsA patients (7.6%) are just as prevalent as in healthy controls (7.5%). 18.5% of PsA patients carrying at least one NOD2 variant underwent joint surgery compared with 4.5% of those without these variants (p=0.019). Multivariate analysis confirmed this finding (OR 8.82, CI 1.7-46.3). There was no requirement for early surgery in patients carrying the NOD2 variants but there was an increased possibility of requiring surgery at similar times of disease duration. No other association with clinical features and NOD2 status carrier was found. CONCLUSIONS: Common NOD2 gene variants are not associated with PsA, but might increase the risk of undergoing joint replacement surgery, suggesting that this autoinflammatory-associated gene could act as a phenotypic modifier gene in PsA patients by increasing the risk of joint destruction. Given the small number of PsA patients with joint surgery included, we consider our findings a new hypothesis that will need further testing.

Copy number variation in the CCL4L gene is associated with susceptibility to acute rejection in lung transplantation.

Lung transplantation (LT) has become an accepted therapy for selected patients with advanced lung disease. One of the main limitations to successful LT is rejection of the transplanted organ where chemokines are pivotal mediators. Here, we test the relationship between copy number variation (CNV) in the CCL4L chemokine gene and rejection risk in LT patients (n=161). Patients with no acute rejection showed a significantly lower mean number of CCL4L copies than patients that showed acute rejection (1.66 vs 1.96, P=0.014), with an even greater number of gene copies seen in patients with more than one episode of acute rejection (1.66 vs 2.30, P=0.001). Additionally, patients with > or =2 CCL4L copies had a significantly higher risk of acute rejection compared with patients that had 0-1 CCL4L copies (odds ratio 2.65; 95% confidence interval, 1.33-5.28; P=0.0046). A combined analysis of CCL4L CNV and the rs4796195 CCL4L single nucleotide polymorphism demonstrated that the effect of CCL4L copy number in acute rejection is mainly because of the number of copies of the CCL4L1 allelic variant. This finding constitutes the first report of CNV as a correlate factor in allograft rejection.