Cost-effectiveness analysis of the diagnosis of temporal arteritis.

Temporal arteritis (TA) is the most common form of systemic vasculitis. Its diagnosis is based on criteria proposed by the American College of Rheumatology (1990), and its treatment is high-dose corticosteroids. Our objective is to assess the cost of diagnosing TA, and secondarily, cost-effective analysis of different diagnostic strategies (clinical, biopsy, doppler ultrasound) and therapeutic strategies (corticosteroid suspension). MATERIAL AND METHOD: Observational, retrospective study has been carried out on patients with AT (2012-2021). Demographic data, comorbidities, signs and symptoms suggestive of AT were collected. AT was diagnosed with a score ≥ 3 according to American College of Rheumatoloy criteria (ACR-SCORE). The costs of diagnosis and treatment modification were analysed. RESULTS: Seventy-five patients have been included, median age 77 (46-87) years. Headache, temporal pain and jaw claudication were significant for the diagnosis of TA. Patients with a halo on Doppler ultrasound and a positive biopsy have significantly elevated ESR and CRP compared to patients who do not. The cost of the AT diagnosis was 414.7 euros/patient. If we use ACR-SCORE ≥ 3-echodoppler it is 167.2 є/patient (savings 59.6%) and ACR-SCORE ≥ 3-biopsy 339.75 є/patient (savings 18%). If the corticosteroid was removed and a biopsy was performed, 21.6 є/patient (94.7% savings), if the corticosteroid was removed and Doppler ultrasound was performed, 10.6 є/patient (97.4% savings). CONCLUSIONS: Headache, temporary pain and jaw claudication are predictors of AT. Elevated ESR and CRP are predictors of positive biopsy and presence of halo on ultrasound. The uses of ACR-SCORE ≥ 3 with Doppler ultrasound or biopsy, and with corticosteroid suspension, are cost-effective.

Análisis coste/efectivo del diagnóstico de la arteritis de la temporal / Cost-effectiveness analysis of the diagnosis of temporal arteritis

La arteritis de la temporal (AT) es la forma más frecuente de vasculitis sistémica, su diagnóstico está basado en criterios propuestos por el Colegio Americano de Reumatología (1990), y su tratamiento son corticoides a dosis elevadas. Nuestro objetivo es valorar el gasto del diagnóstico de la AT, y secundariamente análisis coste/efectivo de distintas estrategias diagnósticas (clínica, biopsia, eco-Doppler) y terapéuticas (suspensión del corticoide). Material y método: Estudio observacional, retrospectivo de pacientes con AT (2012-2021). Se recogieron datos demográficos, comorbilidades, signos y síntomas sugestivos de AT. Se diagnosticó AT con una puntuación ≥3 según los criterios del American College of Reumatology (ACR-SCORE). Se analizaron los gastos del diagnóstico y modificación de tratamiento. Resultados: Setenta y cinco pacientes, mediana edad 77 (6-87) años. Cefalea, dolor temporal y claudicación mandibular fueron significativos para el diagnóstico de AT. Los pacientes con halo en eco-Doppler y biopsia positiva, presentaron elevación de VSG y PCR de forma significativa en comparación con los pacientes que no. El gasto diagnóstico de AT fue de 414,7€/paciente. Si empleamos ACR-SCORE≥3-eco-Doppler serían 167,2€/paciente (ahorro del 59,6%) y ACR-SCORE≥3-biopsia 339,75€/paciente (ahorro del 18%). Si se retiraba corticoide y se realizaba biopsia hubiesen sido 21,6€/paciente (ahorro del 94,7%), si se retiraba corticoide y se realizaba eco-Doppler hubiesen sido 10,6€/paciente (ahorro del 97,4%). Conclusiones: Cefalea, dolor temporal y claudicación mandibular son predictores de AT. La elevación de VSG y PCR son predictores de biopsia positiva y presencia de halo en la ecografía.El empleo de ACR-SCORE≥3 con eco-Doppler o con biopsia, y con suspensión del corticoide son coste/efectivos.(AU)

Temporal arteritis (TA) is the most common form of systemic vasculitis. Its diagnosis is based on criteria proposed by the American College of Rheumatology (1990), and its treatment is high-dose corticosteroids. Our objective is to assess the cost of diagnosing TA, and secondarily, cost-effective analysis of different diagnostic strategies (clinical, biopsy, Doppler ultrasound) and therapeutic strategies (corticosteroid suspension).Material and method: Observational, retrospective study has been carried out on patients with TA (2012–2021). Demographic data, comorbidities, signs and symptoms suggestive of TA were collected. TA was diagnosed with a score ≥3 according to American College of Rheumatoloy criteria (ACR-SCORE). The costs of diagnosis and treatment modification were analysed. Results: Seventy-five patients have been included, median age 77 (46-87) years. Headache, temporal pain and jaw claudication were significant for the diagnosis of TA. Patients with a halo on Doppler ultrasound and a positive biopsy have significantly elevated ESR and CRP compared to patients who do not.: The cost of the TA diagnosis was 414.7 euros/patient. If we use ACR-SCORE≥3-echodoppler it is 167.2 €/patient (savings 59.6%) and ACR-SCORE≥3-biopsy 339.75 €/patient (savings 18%). If the corticosteroid was removed and a biopsy was performed, 21.6 €/patient (94.7% savings), if the corticosteroid was removed and Doppler ultrasound was performed, 10.6 €/patient (97.4% savings).Conclusions: Headache, temporary pain and jaw claudication are predictors of TA. Elevated ESR and CRP are predictors of positive biopsy and presence of halo on ultrasound. The uses of ACR-SCORE≥3 with Doppler ultrasound or biopsy, and with corticosteroid suspension, are cost-effective.(AU)

Topical Immunotherapy for Actinic Keratosis and Field Cancerization.

This comprehensive review delves into various immunotherapeutic approaches for the management of actinic keratoses (AKs), precancerous skin lesions associated with UV exposure. Although there are treatments whose main mechanism of action is immune modulation, such as imiquimod or diclofenac, other treatments, apart from their main effect on dysplastic cells, exert some immunological action, which in the end contributes to their efficacy. While treatments like 5-fluorouracil, imiquimod, photodynamic therapy, and nicotinamide are promising in the management of AKs, especially in immunocompetent individuals, their efficacy is somewhat reduced in solid organ transplant recipients due to immunosuppression. The analysis extends to optimal combination, focusing on cryoimmunotherapy as the most relevant. New immunotherapies include resimiquimod, ingenol disoxate, N-phosphonacetyl-L-aspartate (PALA), or anti-PD1 that have shown promising results, although more studies are needed in order to standardize their use.

Construct Validity of the Gait Deviation Index for People With Incomplete Spinal Cord Injury (GDI-SCI).

BACKGROUND: The Gait Deviation Index for Spinal Cord Injury (SCI-GDI) was recently proposed as a dimensionless multivariate kinematic measure based on 21 gait features derived from 3-dimensional kinematic data which quantifies gait impairment of adult population with incomplete spinal cord injury (iSCI) relative to the normative gait of a healthy group. Nevertheless, no validity studies of the SCI-GDI have been published to date. OBJECTIVE: To assess the construct validity of the SCI-GDI in adult population following iSCI. Methods. SCI-GDI data were obtained from a sample of 50 healthy volunteers and 35 adults with iSCI. iSCI group was also assessed with the following measures: 10-Meter Walk Test (10MWT) at both self-selected (SS) and maximum speeds, Timed Up and Go Test (TUGT), SS and maximum levels of the Walking Index for Spinal Cord Injury (WISCI) II, mobility items of the Spinal Cord Independence Measure III (SCIM IIIIOMob), Lower Extremity Motor Score (LEMS), and Modified Ashworth Scale (MAS). Spearman's correlation coefficient was used to investigate the relationship with the SCI-GDI. RESULTS: SCI-GDI shows strong correlation with the 10MWT (r ≥ -.716) and good correlation with LEMS (r = .638), TUGT (r = -.582), SS WISCI II levels (r = .521), and SCIM IIIIOMob (r = .501). No significant correlations were found with maximum WISCI II levels and MAS (P > .006). CONCLUSIONS: Construct validity of the SCI-GDI was demonstrated with the 10MWT, TUGT, LEMS, SCIM IIIIOMob, and SS WISCI II levels for independently walking adults with iSCI. Future work will include assessing the psychometric characteristics with a more heterogeneous sample, also considering the pediatric population.

Estudio coste-efectividad del diagnóstico de trombosis venosa profunda en el medio hospitalario / Cost-effectiveness study of deep venous thrombosis diagnosis at the hospital setting

Introducción y objetivos: la trombosis venosa profunda (tVP) supone una importante carga económica. nuestro objetivo primario es comparar dos estrategias diagnósticas en cuanto a costes y a efectividad: la prueba del dímero d a todos los pacientes con sospecha con condicionarla a la probabilidad clínica pretest. el secundario, analizar el coste del diagnóstico en nuestro centro y los factores asociados a su presentación. Material y métodos: estudio prospectivo de los pacientes atendidos con sospecha de tVP de extremidad inferior entre mayo y octubre de 2019. Se analizaron las variables de la escala de Wells, el teP asociado, el dímero d, el resultado del eco Doppler y los costes (atención en urgencias, el reactivo del dímero d y la realización de un eco Doppler, obtenidos del Boletín oficial de la comunidad y de la unidad de cobros del hospital). el análisis estadístico se realizó con SPSS, pruebas de χ2 y el test exacto de Fisher. Resultados: se estudiaron 249 pacientes. 116 (46,59 %) presentaron tVP. La edad media fue de 70 años (21-95). aquellos con tVP presentaron con más frecuencia: sexo masculino (52,6 % frente a 39,8 %, p = 0,04), cáncer (29,3 % frente a 16,5 %, p = 0,016), dolor (80,2 % frente a 45,1 %, p < 0,001), edema (93,1 % frente a 57,1 %, p < 0,001), empastamiento (72,4 % frente a 14,3 %, p < 0,001), teP (25,9 % frente a 13,5 %, p = 0,014), menor diagnóstico alternativo (0,9 % frente a 62,4 %, p < 0,001) y menor obesidad (7,8 % frente a 18,8 %, p = 0,011). el gasto generado fue de 192,49 euros por paciente. Para el objetivo primario se analizaron a 144 pacientes (aquellos con dímero d). La estrategia 1 generó un gasto de 190,41 euros por paciente, con una sensibilidad del 100 % y una especificidad del 7,1 %; la estrategia 2, 188,51 euros por paciente, con una sensibilidad del 88,3 % y una especificidad del 78,5 %. ambas estrategias son un 1 % y un 2 % más económicas que el gasto generado, respectivamente...(AU)

Introduction and objective: deep venous thrombosis (dVt) is a significant economic burden. the study primaryendpoint is to compare two diagnostic strategies in terms of cost and effectiveness: d-dimer to all patients withsuspected dVt vs conditioning it to the pre-test clinical probability; the secondary endpoint is to analyze the costof dVt diagnosis in our center and the factors associated with its presentation. Material and methods: this was a prospective study of patients with suspected dVt of lower extremities con-ducted between may and october 2019. the variables of the Wells scale, associated Pte, d-dimer levels, dopplerechocardiography and costs (emergency care, d-dimer and doppler echocardiography obtained from the regionofficial Bulletin and the hospital billing unit) were analyzed. the statistical analysis was performed with SPSS, thechi-square test, and Fisher's exact test. Results: a total of 249 patients were studied, 116 of whom (46.59 %) presented with dVt. the mean age was70 years (21-95). those with dVt were predominantly men (52.6 % vs 39.8 %; p = .04), had cancer (29.3 %vs 16.5 %, p = 0.016), pain (80.2 % vs 45.1 %; p < .001), edema (93.1 % vs 57.1 %, p < .001), slurring (72.4 % vs14.3 %; p < .001), Pte (25.9 % vs 13.5 %, p = .014), less alternative diagnosis (0.9 % vs 62.4 %; p = .001) and lessobesity (7.8 % vs 18.8 %; p = .011). the cost generated was € 192.49 per patient. Regarding the primary endpoint,144 patients (those with d-dimer) were analyzed. Strategy #1 resulted in a cost of €190.41 per patient with100 % sensitivity and 7.1 % specificity; strategy # 2, resulted in a cost of €188.51/patient, with 88.3 % and 78.5 %sensitivity and specificity rates, respectively. Both strategies are 1 % and 2 % cheaper than the cost generated.Conclusion: the application of diagnostic algorithms for suspected dVt is cost-effective, so its use should begeneralized.(AU)

An SPG7 mutation as a novel cause of monogenic progressive muscular atrophy.

BACKGROUND: Progressive muscular atrophy (PMA) is a rare adult-onset neurological disease that is characterized by isolated lower motor neuron degeneration. While it is still disputable whether PMA is a subtype of amyotrophic lateral sclerosis (ALS) or an isolated disorder, it is well-established as a clinically defined entity. About 5% of PMA cases are monogenic, and the implicated genes largely overlap with those causing monogenic ALS. CASE DESCRIPTION: Here we describe a 68-year-old female patient with progressive and asymmetric upper-limb weakness throughout an 18-month period, with muscle atrophy, dysphagia and slurring of speech. The lower limbs were unaffected, and there was no sign of upper motor neuron dysfunction. Comprehensive genetic testing for single nucleotide and copy-number variants revealed a pathogenic monoallelic variant c.1529C>T, p.(Ala510Val) in the SPG7 gene. DISCUSSION: Pathogenic biallelic SPG7 variants have been originally associated with hereditary spastic paraplegia, but other phenotypes are nowadays known to be linked to these variants, such as ALS. However, there is no report of this (or any) other SPG7 variant in association with PMA, whether it progressed to ALS or not. In conclusion, we present the first known case of PMA associated with a monoallelic SPG7 mutation.

Variant in CACNA1G as a Possible Genetic Modifier of Neonatal Epilepsy in an Infant with a De Novo SCN2A Mutation.

Mutations in SCN2A genes have been described in patients with epilepsy, finding a large phenotypic variability, from benign familial epilepsy to epileptic encephalopathy. To explain this variability, it was proposed the existence of dominant modifier alleles at one or more loci that contribute to determine the severity of the epilepsy phenotype. One example of modifier factor may be the CACNA1G gene, as proved in animal models. We present a 6-day-old male newborn with recurrent seizures in which a mutation in the SCN2A gene is observed, in addition to a variant in CACNA1G gene. Our patient suffered in the first days of life myoclonic seizures, with pathologic intercritical electroencephalogram pattern, requiring multiple drugs to achieve adequate control of them. During the next weeks, the patient progressively improved until complete remission at the second month of life, being possible to withdraw the antiepileptic treatment. We propose that the variant in CACNA1G gene could have acted as a modifier of the epilepsy syndrome produced by the mutation in SCN2A gene in our patient.

Exoskeleton-based training improves walking independence in incomplete spinal cord injury patients: results from a randomized controlled trial.

BACKGROUND: In recent years, ambulatory lower limb exoskeletons are being gradually introduced into the clinical practice to complement walking rehabilitation programs. However, the clinical evidence of the outcomes attained with these devices is still limited and nonconclusive. Furthermore, the user-to-robot adaptation mechanisms responsible for functional improvement are still not adequately unveiled. This study aimed to (1) assess the safety and feasibility of using the HANK exoskeleton for walking rehabilitation, and (2) investigate the effects on walking function after a training program with it. METHODS: A randomized controlled trial was conducted including a cohort of 23 patients with less than 1 year since injury, neurological level of injury (C2-L4) and severity (American Spinal Cord Injury Association Impairment Scale [AIS] C or D). The intervention was comprised of 15 one-hour gait training sessions with lower limb exoskeleton HANK. Safety was assessed through monitoring of adverse events, and pain and fatigue through a Visual Analogue Scale. LEMS, WISCI-II, and SCIM-III scales were assessed, along with the 10MWT, 6MWT, and the TUG walking tests (see text for acronyms). RESULTS: No major adverse events were reported. Participants in the intervention group (IG) reported 1.8 cm (SD 1.0) for pain and 3.8 (SD 1.7) for fatigue using the VAS. Statistically significant differences were observed for the WISCI-II for both the "group" factor (F = 16.75, p < 0.001) and "group-time" interactions (F = 8.87; p < 0.01). A post-hoc analysis revealed a statistically significant increase of 3.54 points (SD 2.65, p < 0.0001) after intervention for the IG but not in the CG (0.7 points, SD 1.49, p = 0.285). No statistical differences were observed between groups for the remaining variables. CONCLUSIONS: The use of HANK exoskeleton in clinical settings is safe and well-tolerated by the patients. Patients receiving treatment with the exoskeleton improved their walking independence as measured by the WISCI-II after the treatment.

A Novel Homozygous Splice Site Variant in AIMP1 Gene Causing Hypomyelinating Leukodystrophy: Case Report and Review of the Literature.

BACKGROUND: Biallelic pathogenic variants in AIMP1 gene cause hypomyelinating leukodystrophy type 3, a severe neurodegenerative disorder with early onset characterized by microcephaly, axial hypotonia, epilepsy, spasticity, and developmental delay. METHODS: Clinical exome sequence was performed on patient's DNA and Sanger sequencing was used to confirm the candidate variant. To better characterize the effect of the genetic variant, functional analysis based on Sanger sequencing of the proband's complementary DNA (cDNA) was performed. RESULTS: We report a case of 2-year-old girl with microcephaly, significant global developmental delay, refractory epilepsy, flaccid paralysis, hypomyelination, leukodystrophy, and cerebral atrophy on brain magnetic resonance imaging (MRI). Clinical exome sequencing revealed a novel splice site variant c.603 + 1G > A in homozygosity in the AIMP1 gene. Studies on patient's cDNA showed that the variant disrupts the canonical donor splice site of intron 5, with the recognition of a cryptic splice site within exon 5, leading to the skipping of the last 24 nucleotides of this exon together with the flanking intron. This alteration is predicted to cause an in-frame deletion of eight amino acids (p.Val194_Gln201del) belonging to the tRNA-biding domain of the protein. CONCLUSION: To the best of our knowledge, this is the first report of a splice site variant in the AIMP1 gene causing hypomyelinating leukodystrophy. The description of this patient not only expands the mutational spectrum of AIMP1 but also provides deeper insights on genotype-phenotype correlation by comparing the clinical features of our patient with previously reported affected individuals.

A Randomized Clinical Trial in a Public Health Context: Inclusion of Emotional Techniques in Group Therapy for Anxiety Disorders / Un estudio clínico aleatorizado en un contexto de sanidad pública: inclusión de técnicas emocionales en una terapia grupal para trastornos de ansiedad

Se realizó un ensayo clínico aleatorio con dos grupos de tratamiento: uno que recibió terapia cognitivo-conductual (TCC) y otro con la inclusión de técnicas emocionales (TCCE), ambos de 20 sesiones. La muestra consistió en 237 pacientes, todos ellos con diagnóstico principal de trastornos de ansiedad, y todos remitidos por sus médicos de cabecera. Hubo mejoras significativas en la sintomatología (rasgo de ansiedad, depresión, sintomatología clínica), pero la única diferencia significativa encontrada en la comparación intergrupal fue para la variable "satisfacción vital subjetiva" (p= .017), que fuemayor en el grupo de TCCE. Este grupo también mostró una mayor adherencia al programa de tratamiento (p= .019). Esto refuerza la conveniencia de incluir el tratamiento de terapia de grupo con componentes emocionales en los entornos de atención primaria, destacando la importancia de hacer hincapié en la autoestima.(AU)

A randomized clinical trial was carried out with two treatment groups: one receiving cognitive-behavioral therapy (CBT) and the other with the inclusion of emotional techniques (CEBT), both lasting 20 sessions. The sample consisted of 237 patients, all of them with principal diagnoses of anxiety disorders, and all referred by their general practitioners. There were significant improvements in symptomatology (anxiety trait, depression, clinical symptomatology), but the only significant difference found in the intergroup comparison was for the variable “subjective life satisfaction” (p = .017), which was greater in the CEBT group. This group also displayed better adherence to the treatment program (p = .019). This reinforces the case for including group therapy treatment with emotional components in primary care settings, highlighting the importance of emphasizing self-esteem.(AU)

Genetic Variation in ATXN3 (Ataxin-3) 3'UTR: Insights into the Downstream Regulatory Elements of the Causative Gene of Machado-Joseph Disease/Spinocerebellar Ataxia Type 3.

Untranslated regions are involved in the regulation of transcriptional and post-transcriptional processes. Characterization of these regions remains poorly explored for ATXN3, the causative gene of Machado-Joseph disease (MJD). Although a few genetic modifiers have been identified for MJD age at onset (AO), they only explain a small fraction of the AO variance. Our aim was to analyse variation at the 3'UTR of ATXN3 in MJD patients, analyse its impact on AO and attempt to build haplotypes that might discriminate between normal and expanded alleles.After assessing ATXN3 3'UTR variants in molecularly confirmed MJD patients, an in silico analysis was conducted to predict their functional impact (e.g. their effect on miRNA-binding sites). Alleles in cis with the expanded (CAG)n were inferred from family data, and haplotypes were built. The effect of the alternative alleles on the AO and on SARA and NESSCA ataxia scales was tested.Nine variants, all previously described, were found. For eight variants, in silico analyses predicted (a) deleterious effects (rs10151135; rs55966267); (b) changes on miRNA-binding sites (rs11628764; rs55966267; rs709930) and (c) alterations of RNA-binding protein (RBP)-binding sites (rs1055996; rs910369; rs709930; rs10151135; rs3092822; rs7158733). Patients harbouring the alternative allele at rs10151135 had significantly higher SARA Axial subscores (p = 0.023), comparatively with those homozygous for the reference allele. Ten different haplotypes were obtained, one of which was exclusively found in cis with the expanded and four with the normal allele. These findings, which are relevant for the design of allele-specific therapies, warrant further investigation in independent MJD cohorts.

TREX1 p.A129fs and p.Y305C variants in a large multi-ethnic cohort of CADASIL-like unrelated patients.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and retinal vasculopathy with cerebral leukodystrophy and systemic manifestations (RVCL-S) are the most common forms of rare monogenic early-onset cerebral small vessel disease and share clinical, and, to different extents, neuroradiological and neuropathological features. However, whether CADASIL and RVCL-S overlapping phenotype may be explained by shared genetic risk or causative factors such as TREX1 coding variants remains poorly understood. To investigate this intriguing hypothesis, we used exome sequencing to screen TREX1 protein-coding variability in a large multi-ethnic cohort of 180 early-onset independent familial and apparently sporadic CADASIL-like Caucasian patients from the USA, Portugal, Finland, Serbia and Turkey. We report 2 very rare and likely pathogenic TREX1 mutations: a loss of function mutation (p.Ala129fs) clustering in the catalytic domain, in an apparently sporadic 46-year-old patient from the USA and a missense mutation (p.Tyr305Cys) in the well conserved C-terminal region, in a 57-year-old patient with positive family history from Serbia. In concert with recent findings, our study expands the clinical spectrum of diseases associated with TREX1 mutations.

Pediatric cutaneous mucormicosis.

A 9-year-old boy diagnosed with acute myeloblastic leukemia and undergoing chemotherapy, was admitted with febrile neutropenia. During his admission, several violaceous plaques appeared on the upper extremities and anterior left hemithorax, which worsened and acquired a necrotic center. We performed a biopsy and histology showed a cutaneous infarction at the dermoepidermal and subcutaneous level. We observed abundant wide hyphae with right-angled branching and a culture isolated Rhizopus oryzae. A plastic surgery consultant performed a surgical debridement of the lesions and treatment was started with intravenous amphotericin B. The patient did well on treatment and after almost a month of hospitalization, he was discharged with oral posaconazole. Mucormycosis is an opportunistic fungal infection associated with immunosuppression, particularly involving prematurity and hematological diseases in the pediatric age group. Multiple lesions, as in our case, are infrequent. The clinical presentation is variable. Direct smear or histological observation is the quickest diagnostic technique whereas culture is the most definitive. The combination of surgical debridement and amphotericin B is the treatment with the highest survival rates.

Derivation of the Gait Deviation Index for Spinal Cord Injury.

The Gait Deviation Index (GDI) is a dimensionless multivariate measure of overall gait pathology represented as a single score that indicates the gait deviation from a normal gait average. It is calculated using kinematic data recorded during a three-dimensional gait analysis and an orthonormal vectorial basis with 15 gait features that was originally obtained using singular value decomposition and feature analysis on a dataset of children with cerebral palsy. Ever since, it has been used as an outcome measure to study gait in several conditions, including spinal cord injury (SCI). Nevertheless, the validity of implementing the GDI in a population with SCI has not been studied yet. We investigate the application of these mathematical methods to derive a similar metric but with a dataset of adults with SCI (SCI-GDI). The new SCI-GDI is compared with the original GDI to evaluate their differences and assess the need for a specific GDI for SCI and with the WISCI II to evaluate its sensibility. Our findings show that a 21-feature basis is necessary to account for most of the variance in gait patterns in the SCI population and to provide high-quality reconstructions of the gait curves included in the dataset and in foreign data. Furthermore, using only the first 15 features of our SCI basis, the fidelity of the reconstructions obtained in our population is higher than that when using the basis of the original GDI. The results showed that the SCI-GDI discriminates most levels of the WISCI II scale, except for levels 12 and 18. Statistically significant differences were found between both indexes within each WISCI II level except for 12, 20, and the control group (p < 0.05). In all levels, the average GDI value was greater than the average SCI-GDI value, but the difference between both indexes is larger in data with greater impairment and it reduces progressively toward a normal gait pattern. In conclusion, the implementation of the original GDI in SCI may lead to overestimation of gait function, and our new SCI-GDI is more sensitive to larger gait impairment than the GDI. Further validation of the SCI-GDI with other scales validated in SCI is needed.

Socioeconomic, Clinical, and Molecular Features of Breast Cancer Influence Overall Survival of Latin American Women.

Molecular profile of breast cancer in Latin-American women was studied in five countries: Argentina, Brazil, Chile, Mexico, and Uruguay. Data about socioeconomic characteristics, risk factors, prognostic factors, and molecular subtypes were described, and the 60-month overall cumulative survival probabilities (OS) were estimated. From 2011 to 2013, 1,300 eligible Latin-American women 18 years or older, with a diagnosis of breast cancer in clinical stage II or III, and performance status ≦̸1 were invited to participate in a prospective cohort study. Face-to-face interviews were conducted, and clinical and outcome data, including death, were extracted from medical records. Unadjusted associations were evaluated by Chi-squared and Fisher's exact tests and the OS by Kaplan-Meier method. Log-rank test was used to determine differences between cumulative probability curves. Multivariable adjustment was carried out by entering potential confounders in the Cox regression model. The OS at 60 months was 83.9%. Multivariable-adjusted death hazard differences were found for women living in Argentina (2.27), Chile (1.95), and Uruguay (2.42) compared with Mexican women, for older (≥60 years) (1.84) compared with younger (≤40 years) women, for basal-like subtype (5.8), luminal B (2.43), and HER2-enriched (2.52) compared with luminal A subtype, and for tumor clinical stages IIB (1.91), IIIA (3.54), and IIIB (3.94) compared with stage IIA women. OS was associated with country of residence, PAM50 intrinsic subtype, age, and tumor stage at diagnosis. While the latter is known to be influenced by access to care, including cancer screening, timely diagnosis and treatment, including access to more effective treatment protocols, it may also influence epigenetic changes that, potentially, impact molecular subtypes. Data derived from heretofore understudied populations with unique geographic ancestry and sociocultural experiences are critical to furthering our understanding of this complexity.

The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients.

Purposes: Most molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches. Patients and Methods: We collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival (DFS) stages, was compared. Pathway analyses (GSEA, GSVA and MetaCore) were performed to explore differences among intrinsic subtypes. Results: PAM50 classification of the MPBCS cohort defined 42·6% of tumors as LumA, 21·3% as LumB, 13·3% as HER2E and 16·6% as Basal. Both OSC and DFS for LumA tumors were significantly better than for other subtypes, while Basal tumors had the worst prognosis. While the prognostic power of traditional subtypes calculated with hormone receptors (HR), HER2 and Ki67 determinations showed an acceptable performance, PAM50-derived risk of recurrence best discriminated low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Terms related to both innate and adaptive immune responses were seen predominantly upregulated in Basal tumors, and, to a lesser extent, in HER2E, with respect to LumA and B tumors. Conclusions: This is the first study that assesses molecular features at the transcriptomic level in a multicountry Latin American breast cancer patient cohort. Hormone-related and proliferation pathways that predominate in PAM50 and other breast cancer molecular classifications are also the main tumor-driving mechanisms in this cohort and have prognostic power. The immune-related features seen in the most aggressive subtypes may pave the way for therapeutic approaches not yet disseminated in Latin America. Clinical Trial Registration: ClinicalTrials.gov (Identifier: NCT02326857).

Clinical and Genetic Characterization of Brazilian Patients with Ataxia and Oculomotor Apraxia.

BACKGROUND: Ataxia with oculomotor apraxia (AOA) is characterized by early-onset cerebellar ataxia associated with oculomotor apraxia. AOA1, AOA2, AOA3, and AOA4 subtypes may present pathogenic variants in APTX, SETX, PIK3R5, and PNKP genes, respectively. Mutations in XRCC1 have been found to cause autosomal recessive spinocerebellar ataxia-26 (SCAR26) now considered AOA5. OBJECTIVES: To examine a cohort of Brazilians with autosomal recessive cerebellar ataxia plus oculomotor apraxia and determine the frequencies of AOA subtypes through genetic investigation. METHODS: We evaluated clinical, biomarkers, electrophysiological, and radiological findings of 52 patients with AOA phenotype and performed a genetic panel including APTX, SETX, PIK3R5, PNKP, and XRCC1. RESULTS: We found pathogenic variants in SETX (15 patients), PNKP (12), and APTX (5). No mutations in PIK3R5 or XRCC1 were identified. CONCLUSIONS: AOA2 and AOA4 were the most common forms of AOA in Brazil. Mutations in PIK3R5 and XRCC1 were not part of this genetic spectrum. © 2022 International Parkinson and Movement Disorder Society.

Application of the Gait Deviation Index to Study Gait Impairment in Adult Population With Spinal Cord Injury: Comparison With the Walking Index for Spinal Cord Injury Levels.

The Gait Deviation Index (GDI) is a multivariate measure of overall gait pathology based on 15 gait features derived from three-dimensional (3D) kinematic data. GDI aims at providing a comprehensive, easy to interpret, and clinically meaningful metric of overall gait function. It has been used as an outcome measure to study gait in several conditions: cerebral palsy (CP), post-stroke hemiparetic gait, Duchenne muscular dystrophy, and Parkinson's disease, among others. Nevertheless, its use in population with Spinal Cord Injury (SCI) has not been studied yet. The aim of the present study was to investigate the applicability of the GDI to SCI through the assessment of the relationship of the GDI with the Walking Index for Spinal Cord Injury (WISCI) II. 3D gait kinematics of 34 patients with incomplete SCI (iSCI) was obtained. Besides, 3D gait kinematics of a sample of 50 healthy volunteers (HV) was also gathered with Codamotion motion capture system. A total of 302 (iSCI) and 446 (HV) strides were collected. GDI was calculated for each stride and grouped for each WISCI II level. HV data were analyzed as an additional set. Normal distribution for each group was assessed with Kolmogorov-Smirnov tests. Afterward, ANOVA tests were performed between each pair of WISCI II levels to identify differences among groups (p < 0.05). The results showed that the GDI was normally distributed across all WISCI II levels in both iSCI and HV groups. Furthermore, our results showed an increasing relationship between the GDI values and WISCI II levels in subjects with iSCI, but only discriminative in WISCI II levels 13, 19, and 20. The index successfully distinguished HV group from all the individuals with iSCI. Findings of this study indicated that the GDI is not an appropriate multivariate walking metric to represent the deviation of gait pattern in adult population with iSCI from a normal gait profile when it is compared with the levels of walking impairment described by the WISCI II. Future work should aim at defining and validating an overall gait index derived from 3D kinematic gait variables appropriate for SCI, additionally taking into account other walking ability outcome measures.