Relative cerebral blood volume as response predictor in the treatment of recurrent glioblastoma with anti-angiogenic therapy.

BACKGROUND: Glioblastoma is one of the most common brain tumors in adult populations, usually carrying a poor prognosis. While several studies have researched the impact of anti-angiogenic therapies, especially anti-VEFG treatments in glioblastoma, few have attempted to assess its progress using imaging studies. PURPOSE: We attempted to analyze whether relative cerebral blood volume (rCBV) from dynamic susceptibility-weighted contrast-enhanced MRI (DSC-MRI) could predict response in patients with glioblastoma undergoing Bevacizumab (BVZ) treatment. METHODS: We performed a retrospective study evaluating patients with recurrent glioblastoma receiving anti-angiogenic therapy with BVZ between 2012 and 2017 in our institution. Patients were scheduled for routine MRIs at baseline and first-month follow-up visits. Studies were processed for DSC-MRI, cT1, and FLAIR images, from which relative cerebral blood volume measurements were obtained. We assessed patient response using the Response Assessment in Neuro-Oncology (RANO) working group criteria and overall survival. RESULTS: 40 patients were included in the study and were classified as Bevacizumab responders and non-responders. The average rCBV before treatment was 4.5 for both groups, and average rCBV was 2.5 for responders and 5.4 for non-responders. ROC curve set a cutoff point of 3.7 for rCBV predictive of response to BVZ. Cox Multivariate analysis only showed rCBV as a predictive factor of OS. CONCLUSION: A statistically significant difference was found in rCBV between patients who responded and those who did not respond to BVZ treatment. rCBV may be a low-cost and effective marker to assess response to Bevacizumab treatment in GBM.

Inequity and vulnerability in Latin American Indigenous and non-Indigenous populations with rheumatic diseases: a syndemic approach.

Syndemics are a framework that documents health inequities and vulnerabilities in populations with rheumatic diseases. Compared with other approaches, syndemics are able to conjunctly consider epidemiological, biological, sociodemographic and economic factors, and their interactions. OBJECTIVE: To estimate health inequity and vulnerability among Indigenous and non-Indigenous populations with rheumatic and musculoskeletal diseases (RMD) in Latin America using the syndemic approach. DESIGN: This is a secondary analysis of a previously published large-scale study on the prevalence of RMD. SETTING: Studies carried out in five Latin American countries (Argentina, Colombia, Ecuador, Mexico and Venezuela). Health inequity and vulnerability in RMD were identified through a syndemic approach using network and cluster analysis. PARTICIPANTS: A total of 44 560 individuals were studied: 29.78% self-identified as Indigenous, 60.92% were female, the mean age was 43.25 years. Twenty clusters were identified in the Indigenous population and 17 in the non-Indigenous population. RESULTS: The variables associated with RMD among Indigenous populations were rurality, public health system, high joint biomechanical stress, greater pain, disability and alcoholism; and among non-Indigenous people they were being a woman, urban origin, older age, private health system, joint biomechanical stress, greater pain and disability. We identified different health inequities among patients with RMD (ie, lower educational attainment, more comorbidities), associated with factors such as Indigenous self-identification and rural residence. CONCLUSIONS: A syndemic approach enables us to identify health inequities in RMD, as shown by higher prevalence of comorbidities, disability and socioeconomic factors like lower educational attainment. These inequities exist for the overall population of patients with RMD, although it is more evident in Indigenous groups with added layers of vulnerability.

Assessing the Malignancy Risk of a Meningioma by Its Location.

BACKGROUND: Meningiomas represent 30% of primary intracranial tumors. The current incidence is up to 4.5 cases per 100,000 habitants worldwide. Although there is no prognostic difference among benign histopathological subtypes, atypical meningiomas and malignant meningiomas (WHO grade II and III respectively) may extend to the adjacent brain parenchyma, dura mater, and osseous tissue with a recurrence score (21-49%). This manuscript analyzes the malignancy risk according to neoplastic localization through a logistic retrospective analysis from a total sample of 452 patients with grade I, II, and III (WHO) meningiomas. METHODS: Detailed data collection through a three-year retrospective analysis (January 2008 to December 2011) was applied at Mexico's National Neurology and Neurosurgery Institute including patients with intracranial or spinal-cord meningioma, preoperative imaging study availability and post-surgical histopathological diagnosis. Formal written consent was not required with a waiver by the appropriate national research ethics committee in accordance with the provisions of the regulations of the general health law of Mexico. RESULTS: Convexity lesions displayed an increased risk of malignancy turning for non-benign meningiomas with an odds ratio of 3.1 (95% CI 1.6 to 5.7, p=0.0002) meanwhile skull-base meningiomas present an inverse risk with an odds ratio of 0.4 (95% CI 0.2 to 0.9, p=0.02), as well as spinal-cord meningiomas with an odds ratio of 0.3 (95% CI 0.1 to 0.9). CONCLUSION: Skull base and spinal cord meningiomas usually have benign behavior, meanwhile grade II or III meningiomas within this location are rare. The present work provides an additional criterion for decision making, according to the meningioma's location.

Experiencia sobre el proceso de salud-enfermedad-atención en pacientes con artritis reumatoidea pertenecientes a la comunidad Wichí de Misión Chaqueña "El Algarrobal", Salta / Experience on the health-disease-care process in patients with rheumatoid arthritis belonging to the Wichí community of Mission Chaqueña "El Algarrobal", Salta

Introducción: se ha reportado que la prevalencia de artritis reumatoidea (AR) en la comunidad Wichí representa la más alta informada por el Grupo Latinoamericano para el Estudio de las Enfermedades Reumáticas en los Pueblos Originarios (GLADERPO). El objetivo de este estudio fue describir la experiencia sobre el proceso de salud-enfermedad-atención de pacientes con AR de la comunidad Wichí de Misión Chaqueña "El Algarrobal", Salta. Materiales y métodos: estudio narrativo. Diseño de corte etnográfico. Se realizaron entrevistas semi-estructuradas y observaciones registradas. Se utilizaron guías de entrevistas y observación. Los aspectos incluidos fueron: concepción del proceso salud-enfermedad, percepción de la AR en la vida diaria, el acceso al sistema de salud, utilización de recursos tradicionales y de medicina tradicional. Resultados: se realizaron 10 entrevistas. Los aspectos más relevantes fueron la concepción del proceso salud-enfermedad asociado al trauma social pasado y al concepto de voluntad Wichí. Se evidenció la combinación de estrategias para mejorar el dolor (biomedicina, medicina tradicional y acompañamiento religioso). Además, se observó una relación unidireccional con el sistema de salud. Conclusiones: la AR es una enfermedad con un impacto negativo en la comunidad Wichí. Se requieren otras actividades, desde otras disciplinas, para mejorar el acceso al sistema de salud y la continuidad de los tratamientos.

Introduction: the prevalence of rheumatoid arthritis (RA) in the Wichí community has already been published, representing the highest reported by the Grupo Latinoamericano para el Estudio de las Enfermedades Reumáticas en los Pueblos Originarios (GLADERPO). The objective was to describe the experience of the health-disease-care process of patients with RA from the Wichí community of Misión Chaqueña "El Algarrobal", Salta. Materials and methods: study with ethnographic design. Semi-structured interviews and recorded observations were conducted. Interview and observation guides were used. The aspects included were: conception of the health-disease process; perception of RA in daily life, access to the health system, use of traditional resources and traditional medicine. Results: ten interviews were conducted. The most relevant aspects were the conception of the health-disease process, associated with past social trauma and the concept of "Wichí good will". The combination of strategies to improve pain (biomedicine, traditional medicine and religious accompaniment) was evidenced. In addition, a unidirectional relationship with the health system was observed. Conclusions: RA is a disease with a negative impact on the Wichí community. Other activities from other disciplines are necessary to improve access to the health system and continuity of treatment.

Primary Sjögren syndrome and development of another autoimmune rheumatic disease during the follow-up.

BACKGROUND: Primary Sjögren syndrome (pSS) is a chronic autoimmune disease with its main target being exocrine glands, and is the connective tissue disease more frequently associated with other autoimmune diseases. The aim of this study was to assess the frequency of another autoimmune rheumatic disease (ARD) developed in primary Sjögren syndrome (pSS) patients and to describe it's clinical, serological and histologic characteristics. MATERIALS AND METHODS: This is a retrospective cohort study. Data of patients with pSS diagnosis (American-European criteria 2002), included in the GESSAR database (Grupo de Estudio Síndrome de Sjögren, Sociedad Argentina de Reumatología) were analyzed. The development of a second ARD was registered during the follow up. RESULTS: 681 patients were included, 94.8% female. The mean age was 54 (SD 14) years and mean age at diagnosis of 50 (SD 13) years. The mean follow-up was 4.7 (SD 4.9) years; 30 patients (4.41%, CI 95%: 3.1-5.7) developed a second ARD during the follow up, incidence rate was 9.1/1000 patients-year (IR 95%: 5.8-12.4/1000 patients-year), the most frequent being rheumatoid arthritis (RA). 96% out of these 30 patients had xerophthalmia, 86.2% xerostomia, 92% positive Schirmer test, 88.24% positive Rosa Bengala test, lisamine green or Ocular Staining Score, 81.2% positive unstimulated salivary flow, 82.1% Ro(+) and 33.33% La(+). Minor salivary gland biopsy had been performed in 14 of the 30 patients, 12 with positive results. There were no statistically significant differences respect baseline characteristics when comparing the patients who developed another ARD to the ones that did not. CONCLUSIONS: Of all the patients analyzed, 4.4% presented another ARD during their follow-up. It is important to be aware of this, to make an early and proper diagnosis and treatment of our patients.

Clinical and Serological Features in Latin American IgG4-Related Disease Patients Differ According to Sex, Ethnicity, and Clinical Phenotype.

BACKGROUND/OBJECTIVE: Data on IgG4-related disease (IgG4-RD) come almost exclusively from cohorts from Asia, Europe, and North America. We conducted this study to describe the clinical presentation, phenotype distribution, and association with sex, ethnicity, and serological markers in a large cohort of Latin American patients with IgG4-RD. METHODS: We performed a multicenter medical records review study including 184 Latin American IgG4-RD patients. We assigned patients to clinical phenotypes: group 1 (pancreato-hepato-biliary), group 2 (retroperitoneal/aortic), group 3 (head and neck-limited), group 4 (Mikulicz/systemic), and group 5 (undefined). We focused the analysis on how sex, ethnicity, and clinical phenotype may influence the clinical and serological presentation. RESULTS: The mean age was 50.8 ± 15 years. Men and women were equally affected (52.2% vs 48.8%). Fifty-four patients (29.3%) were assigned to group 1, 21 (11.4%) to group 2, 57 (30.9%) to group 3, 32 (17.4%) to group 4, and 20 (10.8%) to group 5. Male sex was associated with biliary tract (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.36-8.26), kidney (OR, 3.4; 95% CI, 1.28-9.25), and retroperitoneal involvement (OR, 5.3; 95% CI, 1.45-20). Amerindian patients presented more frequently with atopy history and gallbladder involvement. Group 3 had a female predominance. CONCLUSIONS: Latin American patients with IgG4-RD were younger, and men and women were equally affected compared with White and Asian cohorts. They belonged more commonly to group 1 and group 3. Retroperitoneal and aortic involvement was infrequent. Clinical and serological features differed according to sex, ethnicity, and clinical phenotype.

Primary Sjögren syndrome and development of another autoimmune rheumatic disease during the follow-up

Abstract Background: Primary Sjögren syndrome (pSS) is a chronic autoimmune disease with its main target being exocrine glands, and is the connective tissue disease more frequently associated with other autoimmune diseases. The aim of this study was to assess the frequency of another autoimmune rheumatic disease (ARD) developed in primary Sjögren syndrome (pSS) patients and to describe it's clinical, serological and histologic characteristics. Materials and methods: This is a retrospective cohort study. Data of patients with pSS diagnosis (American-European criteria 2002), included in the GESSAR database (Grupo de Estudio Síndrome de Sjögren, Sociedad Argentina de Reumatología) were analyzed. The development of a second ARD was registered during the follow up. Results: 681 patients were included, 94.8% female. The mean age was 54 (SD 14) years and mean age at diagnosis of 50 (SD 13) years. The mean follow-up was 4.7 (SD 4.9) years; 30 patients (4.41%, CI 95%: 3.1-5.7) developed a second ARD during the follow up, incidence rate was 9.1/1000 patients-year (IR 95%: 5.8-12.4/1000 patients-year), the most frequent being rheumatoid arthritis (RA). 96% out of these 30 patients had xerophthalmia, 86.2% xerostomia, 92% positive Schirmer test, 88.24% positive Rosa Bengala test, lisamine green or Ocular Staining Score, 81.2% positive unstimulated salivary flow, 82.1% Ro(+) and 33.33% La(+). Minor salivary gland biopsy had been performed in 14 of the 30 patients, 12 with positive results. There were no statistically significant differences respect baseline characteristics when comparing the patients who developed another ARD to the ones that did not. Conclusions: Of all the patients analyzed, 4.4% presented another ARD during their follow-up. It is important to be aware of this, to make an early and proper diagnosis and treatment of our patients. Key points Patients with primary Sjögren's Syndrome may develop another connective tissue disease during follow-up. The most frequently connective tissue disease developed during follow-up in the population of patients with primary Sjogren's Syndrome studied was rheumatoid arthritis. It is important to be aware of this to make an early and proper diagnosis.

Midkine Interaction with Chondroitin Sulfate Model Synthetic Tetrasaccharides and Their Mimetics: The Role of Aromatic Interactions.

Midkine (MK) is a neurotrophic factor that participates in the embryonic central nervous system (CNS) development and neural stem cell regulation, interacting with sulfated glycosaminoglycans (GAGs). Chondroitin sulfate (CS) is the natural ligand in the CNS. In this work, we describe the interactions between a library of synthetic models of CS-types and mimics. We did a structural study of this library by NMR and MD (Molecular Dynamics), concluding that the basic shape is controlled by similar geometry of the glycosidic linkages. Their 3D structures are a helix with four residues per turn, almost linear. We have studied the tetrasaccharide-midkine complexes by ligand observed NMR techniques and concluded that the shape of the ligands does not change upon binding. The ligand orientation into the complex is very variable. It is placed inside the central cavity of MK formed by the two structured beta-sheets domains linked by an intrinsically disordered region (IDR). Docking analysis confirmed the participation of aromatics residues from MK completed with electrostatic interactions. Finally, we test the biological activity by increasing the MK expression using CS tetrasaccharides and their capacity in enhancing the growth stimulation effect of MK in NIH3T3 cells.

Expresión clínica del Síndrome de Sjögren primario en pacientes adultos diagnosticados a edad menor o igual a 35 años versus mayores de 35 años / Clinical expression of primary Sjögren's syndrome in adult patients diagnosed at an age less than or equal to 35 years versus those older than 35 years

Objetivo: Describir y comparar las manifestaciones clínicas en pacientes adultos diagnosticados con Síndrome de Sjögren primario (SSp) a edad menor o igual a 35 años versus mayores a 35 años. Materiales y métodos: Se incluyeron pacientes mayores de 18 años de edad, con diagnóstico de SSp de acuerdo a los criterios de clasificación ACR - EULAR 2002/2016, registrados en la base de datos GESSAR (Grupo de Estudio Síndrome de Sjögren Sociedad Argentina de Reumatología). Resultados: Se incluyeron 665 pacientes. Cien (15,04%) con edad al diagnóstico ≤ 35 años, 92% mujeres. El promedio de edad del grupo > 35 años, fue de 54 + 11 años, 96% mujeres. Se encontraron diferencias estadísticamente significativas entre < 35 años vs > 35 años, en xeroftalmia (90,72% vs 95,64%, p: 0,04) y xerodermia (42,35% vs 57,36%, p: 0,03) y en los siguientes dominios del ESSDAI (EULAR Activity Index for primary Sjögren's syndrome): sistema nervioso periférico (4,05 vs 11,32, p: 0,03), respiratorio (6% vs 15,40%, p: 0,01) y renal (6% vs 1,59%, p: 0,02). Conclusión: Nuestro estudio sugiere un menor compromiso glandular en pacientes con SSp diagnosticados a menor edad, sin un patrón diferencial característico en cuanto al compromiso sistémico.

Objective: To describe and compare the clinical manifestations, in adult patients diagnosed with primary Sjögren's Syndrome at age less than or equal to 35 years versus those over 35 years of age. Materials and Methods: We analyzed the data of patients older than 18 years, with diagnosis of primary Sjögren's syndrome (American - European criteria 2002), included in the GESSAR database (Sjögren Syndrome Study Group of the Argentine Society of Rheumatology). Results: 665 patients were included. One hundred of them with an age at diagnosis less than or equal to 35 years and with a mean age at diagnosis of 29 + 4 years, 92% of them women. The average age at diagnosis of the group over 35 years was 54 + 11 years, 96% women. Statistically significant differences were found between less than or equal to 35 years vs over 35 years, in xerophthalmia (90.72% vs 95.64%, p: 0.04) and xeroderma (42.35% vs 57.36% , p: 0.03), and in the following domains of ESSDAI (EULAR Activity Index for primary Sjögren's syndrome): peripheral nervous system (4.05 vs 11.32, p: 0.03), respiratory (6% vs 15.40%, p: 0.01) and renal (6% vs 1.59%, p: 0.02). Conclusion: Our study suggests less glandular involvement in patients with pSS diagnosed at a younger age, without a characteristic differential pattern regarding systemic involvement.

The Sumo proteome of proliferating and neuronal-differentiating cells reveals Utf1 among key Sumo targets involved in neurogenesis.

Post-translational modification by covalent attachment of the Small ubiquitin-like modifier (Sumo) polypeptide regulates a multitude of processes in vertebrates. Despite demonstrated roles of Sumo in the development and function of the nervous system, the identification of key factors displaying a sumoylation-dependent activity during neurogenesis remains elusive. Through a SILAC (stable isotope labeling by/with amino acids in cell culture)-based proteomic approach, we have identified the Sumo proteome of the model cell line P19 under proliferation and neuronal differentiation conditions. More than 300 proteins were identified as putative Sumo targets differentially associated with one or the other condition. A group of proteins of interest were validated and investigated in functional studies. Among these, Utf1 was revealed as a new Sumo target. Gain-of-function experiments demonstrated marked differences between the effects on neurogenesis of overexpressing wild-type and sumoylation mutant versions of the selected proteins. While sumoylation of Prox1, Sall4a, Trim24, and Utf1 was associated with a positive effect on neurogenesis in P19 cells, sumoylation of Kctd15 was associated with a negative effect. Prox1, Sall4a, and Kctd15 were further analyzed in the vertebrate neural tube of living embryos, with similar results. Finally, a detailed analysis of Utf1 showed the sumoylation dependence of Utf1 function in controlling the expression of bivalent genes. Interestingly, this effect seems to rely on two mechanisms: sumoylation modulates binding of Utf1 to the chromatin and mediates recruitment of the messenger RNA-decapping enzyme Dcp1a through a conserved SIM (Sumo-interacting motif). Altogether, our results indicate that the combined sumoylation status of key proteins determines the proper progress of neurogenesis.

A Clinical Prognostic Scoring System for Neurocysticercosis.

Objectives In patients with neurocysticercosis (NCC), an accurate risk prediction would allow a better therapeutic approach; however, there are currently no tools that can enhance the accuracy of risk prediction. We designed a prognostic scoring system to be used by neurologists and other physicians managing patients with NCC. Materials and Methods Using data from clinical records of patients from a third-level national reference center for neurological diseases, we assessed demographic, clinical, and tomographic variables among 293 patients diagnosed with NCC. Multivariable logistic regression analyses were used to develop a clinical prognostic scoring instrument. Patients with NCC were assessed for neurological impairment at 3 months after diagnosis. Statistical Analysis Score accuracy was assessed by receiver operating characteristic (ROC) curve analysis. The primary outcome was the presence of neurological impairment, resulting in disability according to self-report or caregiver reports; this outcome was assessed during follow-up visits at 3 ± 1 months after discharge. Results The most common symptoms at presentation were headache (67%) and seizure (63%). A six-item (total score from -4 to + 2) prognostic instrument was constructed on the basis of the presence of seizures/headache at presentation, a leukocyte count above 12x 109/dL, the presence of six to ten parasites, subarachnoid localization, and the use of anthelmintic drugs. Among 113 patients with negative scores, 79.6% developed neurological deficits. Among patients with scores of 1 to 2, 64.6% recovered completely, with an overall accuracy of prediction of 74.7% and area under the ROC curve = 0.722 (95% CI, 0.664-0.780, p < 0.0001). Conclusions The clinical prognostic scoring system for NCC described in this study is a new instrument for use in daily clinical practice. It is simple to administer, and it has a prognostic accuracy of 75%. Its use has the potential to improve the quality of care by guiding appropriate decision-making and early management of patients with NCC.

Prevalence of musculoskeletal disorders and rheumatic diseases in an Argentinean indigenous Wichi community.

OBJECTIVE: To estimate the prevalence of musculoskeletal disorders (MSK) and rheumatic diseases in an indigenous Wichi population in Argentina. METHODS: This is a cross-sectional, community-based study using the Community-Oriented Program for the Control of Rheumatic Diseases (COPCORD) methodology in ≥ 18-year-old subjects. Validated surveys were conducted by trained interviewers. Subjects with MSK pain (positive cases) were evaluated by internists and rheumatologists for diagnosis and treatment. RESULTS: A total of 648 interviews were performed (90.4% of the census population). Mean age was 37.5 years (SD 14.8), and 379 (58.5%) were female. The mean years of education was 7.0 (SD 3.7); 552 subjects (85.2%) were covered by the public health care system. A total of 216 (33.3%) subjects had MSK pain in the last 7 days. Rheumatic disease prevalence was as follows: mechanical back pain (19.0%), rheumatic regional pain syndrome (5.2%), osteoarthritis (3.2%), rheumatoid arthritis (RA) (3.2%), inflammatory back pain (1.2%), undifferentiated arthritis (0.3%), Sjögren syndrome (0.15%), and fibromyalgia (0.15%). RA patients included 19 (90.5%) women and 9 (42.9%) with RA family history. One hundred percent were seropositive and 66.7% showed radiologic erosions. The mean of Disease Activity Score [DAS-28 (ESR)] at the time of diagnosis was 5.1 (SD 1.5) and the Health Assessment Questionnaire Disability Index (HAQ-DI) was 0.8 (SD 0.4). CONCLUSION: RA prevalence was 3.2%, one of the highest reported using the COPCORD methodology in indigenous and non-indigenous peoples in Latin America, with a high percentage of family cases. Pain and functional capacity were the variables allowing patients' early referral to a specialist. Key Points • The RA prevalence was 3.2%, one of the highest reported using COPCORD methodology in indigenous and non-indigenous peoples in Latin America. • The patients with RA had high percentage of familiar history of RA. • The pain and functional capacity were the variables associated with a diagnosis of any rheumatic disease and should be considered for early referral. • The mean of the delay in the diagnosis was 5.8 years. In this community, the lack of the "migration health" phenomenon may be a social determinant that negatively impacts their health.

Asociación entre Artritis Reumatoidea y otras enfermedades autoinmunes / Association between Rheumatoid Arthritis and other autoimmune diseases

Objetivos: Determinar la frecuencia de enfermedades autoinmunes (EAI) en pacientes con Artritis Reumatoidea (AR) y comparar la frecuencia de EAI entre pacientes con AR y sin AR ni otra EAI reumatológica. Material y Métodos: Estudio multicéntrico, observacional, analítico, retrospectivo. Se incluyeron pacientes consecutivos con AR (ACR/EULAR 2010) y como grupo control pacientes con diagnóstico inicial de Osteoartritis primaria (OA). Resultados: Se incluyeron 1549 pacientes: 831 con AR (84% mujeres, edad media 55.2 años [DE 13.6]) y 718 con OA (82% mujeres, edad media 67 años [DE 11.1]). La frecuencia de EAI en el grupo AR fue del 22% (n=183). Estos presentaron mayor frecuencia de EAI reumatológicas (9.4 vs 3.3%, p< 0.001), y menor frecuencia de EAI no reumatológicas que aquellos con OA (15.3 vs 20.5, p=0.007). La EAI reumatológica más prevalente fue el Síndrome de Sjögren, el cual fue más frecuente en el grupo AR (87.2 vs 29.2%, p< 0,001). La frecuencia de EAI reumatológicas en los pacientes con AR fue mayor en la forma erosiva (11 vs 6.8%, p=0.048). Conclusión: La frecuencia de EAI en los pacientes con AR fue del 22%, en quienes predominaron las de etiología reumatológica mientras que, las no reumatológicas predominaron en pacientes con OA.

Objectives: To determine the frequency of autoimmune diseases (AID) in Rheumatoid Arthritis (RA) patients and to compare this frequency between patients with and without RA or other rheumatologic AID. Methods: Multicenter, observational, analytical, retrospective study. Consecutive patients with diagnosis of RA (ACR/EULAR 2010) were included. Patients with initial diagnosis of primary ostearthritis (OA) were used as control group. Results: A total of 1549 patients were included: 831 RA (84% women, mean age 55.2 [±13.6]) and 718 OA (82% women, mean age 67 [± 11.1]). The frequency of AID in the RA group was 22% (n=183). RA patients showed higher frequency of rheumatologic AID (9.4 vs 3.3%, p< 0.001), and lower frequency of non-rheumatologic AID than OA patients (15.3 vs 20.5%, p= 0.007). The most prevalent rheumatic AID was Sjögren's Syndrome, which was more frequent in the AR group (87.2 vs 29.2%, p<0.001). The frequency of rheumatologic AID in RA patients was higher in those with erosive RA (11 vs 6.8%, p=0.048). Conclusion: The frequency of AID in RA patients was 22%. Rheumatologic AID were more frequent in RA patients, whereas non-rheumatologic AID prevailed in OA patients.

Syndemic and syndemogenesis of low back pain in Latin-American population: a network and cluster analysis.

INTRODUCTION: Although low back pain (LBP) is a high-impact health condition, its burden has not been examined from the syndemic perspective. OBJECTIVE: To compare and assess clinical, socioeconomic, and geographic factors associated with LBP prevalence in low-income and upper-middle-income countries using syndemic and syndemogenesis frameworks based on network and cluster analyses. METHODS: Analyses were performed by adopting network and cluster design, whereby interrelations among the individual and social variables and their combinations were established. The required data was sourced from the databases pertaining to the six Latin-American countries. RESULTS: Database searches yielded a sample of 55,724 individuals (mean age 43.38 years, SD = 17.93), 24.12% of whom were indigenous, and 60.61% were women. The diagnosed with LBP comprised 6.59% of the total population. Network analysis showed higher relationship individuals' variables such as comorbidities, unhealthy habits, low educational level, living in rural areas, and indigenous status were found to be significantly associated with LBP. Cluster analysis showed significant association between LBP prevalence and social variables (e.g. Gender inequality Index, Human Development Index, Income Inequality). CONCLUSIONS: LBP is a highly prevalent condition in Latin-American populations with a high impact on the quality of life of young adults. It is particularly debilitating for women, indigenous individuals, and those with low educational level, and is further exacerbated by the presence of comorbidities, especially those in the mental health domain. Thus, the study findings demonstrate that syndemic and syndemogenesis have the potential to widen the health inequities stemming from LBP in vulnerable populations. Key points • Syndemic and syndemogenesis evidence health disparities in Latin-American populations, documenting the complexity of suffering from a disease such as low back pain that is associated with comorbidities, unhealthy habits, and the social and regional context where they live. • The use of network and cluster analyses are useful tools for documenting the complexity and the multifaceted impact in health in large populations as well as the differences between countries. • The variability and impact of socioeconomic indicators (e.g., Gini index) related to low back pain and comorbidities could be felt through the use of cluster analysis, which generates evidence of regional inequality in Latin America. • Populations can be studied from different models (network and cluster analysis) and grouping, presenting new interpretations beyond geographical groupings, such as syndemic and inequity in health.

The Comparative Treatment of Intraventricular Chemotherapy by Ommaya Reservoir vs. Lumbar Puncture in Patients With Leptomeningeal Carcinomatosis.

Object: Leptomeningeal Carcinomatosis (LCM) represents a state of systemic malignant disease with poor prognosis. The purpose of this study is to compare overall survival (OS) between intraventricular chemotherapy through Ommaya reservoir (OR) and chemotherapy through lumbar puncture (LP) in LCM. Patients and Methods: Forty adult patients with LCM were included. All patients underwent lumbar puncture and Magnetic resonance imaging (MRI). Thirty patients received chemotherapy through LP and 10 undergone colocation of Ommaya reservoir for intraventricular chemotherapy. Results: The most common symptom was headache (Present in 50%). The cranial nerves most affected were VI and VII. Leptomeningeal enhancement was the most frequent finding in MRI. The OS in the LP group was 4 months and Ommaya group was 9.2 months (p = 0.0006; CI:1.8-3), with statistical differences in favor to Intraventricular treatment. Proportional hazard regression showed that receiving chemotherapy through Ommaya reservoir was a protective factor (Hazard ratio = 0.258, Standard Error = 0.112, p = 0.002 and 95% CI 0.110-0.606). Using KPS as a factor did not affect the hazard ratio of Ommaya reservoir itself. Conclusions: OS was significantly higher in patients with Ommaya reservoir in spite of Karnofsky Performance Status (KPS) previous to chemotherapy. Therefore, intraventricular chemotherapy should be preferred over lumbar puncture chemotherapy administration if there are resources available.

[Primary Tumors of the Central Nervous System. Clinical Experience at a Third Level Center].

Background: Central nervous system (CNS) tumors are a group of neoplasms that originate from various cells in the CNS. The increasing incidence and prevalence of this type of tumor in developing countries are striking; however, there are few current studies in Latin America including Mexico estimating the impact of these pathological entities on the general population. Objective: The objective of the study was to study the characteristics of primary CNS tumors over a period of 52 years. Methods: A review of records from patients with a histopathological diagnosis of CNS neoplasm over a period of 52 years was conducted at a tertiary-care academic medical center. Patients were grouped by sex, age, and the tumor's anatomical location. Results: A sample of 9615 patients with tumor lesions was obtained; 51% were female, 49% were male, and their mean age was 42 years. The tumors with the highest prevalence were neuroepithelial tumors (38.6%), followed by meningeal tumors (22.8%). Neuroepithelial tumors accounted for 64% in the group of patients under 40 years of age and 56% among those above 40 years of age. The most frequently involved location was supratentorial, in 78.9% of cases. Conclusions: Although retrospective in nature and based on a small sample, this study reports the epidemiology and characteristics of primary brain tumors in the Mexican population.

The Diabetes-Linked Transcription Factor PAX4: From Gene to Functional Consequences.

Paired box 4 (PAX4) is a key factor in the generation of insulin producing ß-cells during embryonic development. In adult islets, PAX4 expression is sequestered to a subset of ß-cells that are prone to proliferation and more resistant to stress-induced apoptosis. The importance of this transcription factor for adequate pancreatic islets functionality has been manifested by the association of mutations in PAX4 with the development of diabetes, independently of its etiology. Overexpression of this factor in adult islets stimulates ß-cell proliferation and increases their resistance to apoptosis. Additionally, in an experimental model of autoimmune diabetes, a novel immunomodulatory function for this factor has been suggested. Altogether these data pinpoint at PAX4 as an important target for novel regenerative therapies for diabetes treatment, aiming at the preservation of the remaining ß-cells in parallel to the stimulation of their proliferation to replenish the ß-cell mass lost during the progression of the disease. However, the adequate development of such therapies requires the knowledge of the molecular mechanisms controlling the expression of PAX4 as well as the downstream effectors that could account for PAX4 action.

Long-term Outcome of Lupus Nephritis Class II in Argentine Patients: An Open Retrospective Analysis.

BACKGROUND: There is controversy in medical literature over the outcome of patients with lupus nephritis (LN) class II. The aim of this study was to explore the risk of histological transformation (HT) and possible factors related to negative response to treatment in patients with mesangial LN class II. METHODS: A retrospective and multicenter study was carried out that includes patients who had received a diagnosis of LN class II on their first renal biopsy. Creatinine, urine sediment, and proteinuria were recorded at the time of the first biopsy, 6 months, and 1, 2, and 5 years after the first biopsy. Response to treatment, HT, and long-term outcome were evaluated. RESULTS: Forty-one patients were included. The manifestation at first biopsy was proteinuria greater than 0.5 g/d in 28 patients (68.29%; 8 [28.57%] of 28 patients had nephrotic syndrome), hematuria in 18 patients (43.90%), and deterioration of renal function in 3 patients (7.31%). During the follow-up (median, 8 years; range, 1-35 years), a new biopsy was performed in 18 patients (43.90%), and in 17 patients (17/18 [94.44%]), there was HT. Median time at rebiopsy was 32 months (range, 11-305 months). Of the 18 patients who had a second biopsy, 10 (55.55%) were on hydroxychloroquine versus 100% (19/19) of patients who did not undergo the procedure (P = 0.001). A year after the first renal biopsy, there are data available from 34 patients; of them, 24 patients (70.58%) had achieved response, and 10 patients (29.41%) had no response (NR) (missing data in 7). A higher 24-hour urinary protein at 6 months was predictor of worse outcome at 1 year, with statistical significance difference for the nonresponder group (median proteinuria, 2.3 g/d [range, 0-4.7 g/d]) compared with responders (median proteinuria, 0.28 g/d [range, 0-1.7 g/d]) (P = 0.0133).In the long-term follow-up (5 years), HT was the main cause of unfavorable outcome and was measured in 78.57% of patients (11/14 patients). CONCLUSIONS: This series shows a high rate of HT in long-term follow-up. Proteinuria at 6 months made it possible to set aside patients who will have an unfavorable outcome in the long term and who will thus benefit from a more aggressive treatment. The results suggest that hydroxychloroquine had a nephroprotective effect.

The Sumo protease Senp7 is required for proper neuronal differentiation.

Covalent attachment of the Small ubiquitin-like modifier (Sumo) polypeptide to proteins regulates many processes in the eukaryotic cell. In the nervous system, Sumo has been associated with the synapsis and with neurodegenerative diseases. However, its involvement in regulating neuronal differentiation remains largely unknown. Here we show that net Sumo deconjugation is observed during neurogenesis and that Sumo overexpression impairs this process. In an attempt to shed light on the underlying mechanisms, we have analyzed the expression profile of genes coding for components of the sumoylation pathway following induction of neuronal differentiation. Interestingly, we observed strong upregulation of the Senp7 protease at both mRNA and protein levels under differentiation conditions. Sumo proteases, by removing Sumo from targets, are key regulators of sumoylation. Strikingly, loss-of-function analysis demonstrated that Senp7 is required for neuronal differentiation not only in a model cell line, but also in the developing neural tube. Finally, reporter-based analysis of the Senp7 promoter indicated that Senp7 was transiently activated at early stages of neuronal differentiation. Thus, the Sumo protease Senp7 adds to the list of factors involved in vertebrate neurogenesis.

Effects of cigarette smoking on early arthritis: a cross-sectional study-data from the Argentine Consortium for Early Arthritis (CONAART).

Our objective was to analyze the effects of cigarette smoking on disease activity, functional capacity, radiographic damage, serology and presence of extraarticular manifestations in patients with rheumatoid arthritis and undifferentiated arthritis. This is a cross-sectional study of 1,305 patients (729 with rheumatoid arthritis and 576 with undifferentiated arthritis) from CONAART, the Argentine Consortium for Early Arthritis that includes patients older than 16 years with <2 years of disease. Sociodemographic data, clinical characteristics of the disease and smoking history were collected. In patients with rheumatoid arthritis the disease activity score of 28 joints was 5.4 ± 1.3 in current smokers, 5.2 ± 1.4 in former smokers and 5.1 ± 1.4 in never smokers (p = 0.011). The simple erosion narrowing score was higher in current smokers and former smokers than in never smokers (M 14.0, R Q 6.0-21.0; M 15.0, R Q 7.0-24.0; M 10.0, R Q 5.0-17.0; p = 0.006). Current smokers had higher rheumatoid factor titer (M 160.0, R Q 80.0-341.0) than former smokers (M 146.8, R Q 6.03-255.5) and never smokers (M 15.0, R Q 9.0-80.0) (p = 0.004). The variable independently associated with tobacco exposure was simple erosion narrowing score (OR = 1.03, 95 % CI 1.00-1.05; p = 0.012). In patients with undifferentiated arthritis, an association between smoking status and parameters of activity or radiographic damage was not observed. Neither was tobacco exposure related to the presence of extraarticular manifestations or to the degree of disability in any of the two groups of patients. No relation was found between disease activity and severity, and number of packs smoked per year. Tobacco.