Proximity extension assay proteomics and renal single cell transcriptomics uncover novel urinary biomarkers for active lupus nephritis.

OBJECTIVE: To identify urinary biomarkers that can distinguish active renal involvement in Lupus Nephritis (LN), a severe manifestation of systemic lupus erythematosus (SLE). METHODS: Urine from 117 subjects, comprised of inactive SLE, active non-renal lupus, active LN, and healthy controls, were subjected to Proximity Extension Assay (PEA) based comprehensive proteomics followed by ELISA validation in an independent, ethnically diverse cohort. Proteomic data is also cross-referenced to renal transcriptomic data to elucidate cellular origins of biomarkers. RESULTS: Systems biology analyses revealed progressive activation of cytokine signaling, chemokine activity and coagulation pathways, with worsening renal disease. In addition to validating 30 previously reported biomarkers, this study uncovers several novel candidates. Following ELISA validation in an independent cohort of different ethnicity, the six most discriminatory biomarkers for active LN were urinary ICAM-2, FABP4, FASLG, IGFBP-2, SELE and TNFSF13B/BAFF, with ROC AUC ≥80%, with most correlating strongly with clinical disease activity. Transcriptomic analyses of LN kidneys mapped the likely origin of these proteins to intra-renal myeloid cells (CXCL16, IL-1RT2, TNFSF13B/BAFF), T/NK cells (FASLG), leukocytes (ICAM2) and endothelial cells (SELE). CONCLUSION: In addition to confirming the diagnostic potential of urine ALCAM, CD163, MCP1, SELL, ICAM1, VCAM1, NGAL and TWEAK for active LN, this study adds urine ICAM-2, FABP4, FASLG, IGFBP-2, SELE, and TNFSF13B/BAFF as additional markers that warrant systematic validation in larger cross-sectional and longitudinal cohorts.

Reporte de caso: síndrome de absorción intravascular en histeroscopia, intoxicación por glicina / Case report: Intravascular absorption syndrome in hysteroscopy, glycine intoxication

El síndrome de absorción intravascular en histeroscopia se origina por la rápida absorción vascular de soluciones isotónicas e hipotónicas utilizadas en irrigación intrauterina, ocasionando hipervolemia y dilución de electrolitos, especialmente hiponatremia. Cuando este síndrome es debido a intoxicación por glicina al 1,5% causa acidosis severa y neurotoxicidad. La incidencia de este síndrome es baja pero puede aumentar por factores como: falta de control de altura de bolsas de irrigación, ausencia de equilibrio de fluidos de soluciones de irrigación, tejidos altamente vascularizados como miomas uterinos y uso de sistema de electrocirugía monopolar. Se reporta el caso de una paciente con miomas uterinos, programada para resección mediante histeroscopia que cursa con síndrome de absorción intravascular por glicina, el temprano diagnóstico y rápido tratamiento intraoperatorio y postoperatorio permitió una evolución favorable. El manejo se basó en el uso de diuréticos, restricción de fluidos y soluciones hipertónicas de sodio.

Intravascular absorption syndrome in hysteroscopy is caused by rapid vascular absorption of isotonic and hypotonic solutions used in intrauterine irrigation, causing hypervolemia and electrolyte dilution, especially hyponatremia. When this syndrome is due to 1.5% glycine toxicity, it causes severe acidosis and neurotoxicity. The incidence of this syndrome is low but may increase due to factors such as: lack of control of the height of irrigation bags, lack of fluid balance in irrigation solutions, highly vascularized tissues such as uterine myomas and use of a monopolar electrosurgery system. The case of a patient with uterine myomas, scheduled for resection by hysteroscopy, who presents with intravascular glycine absorption syndrome, is reported. Early diagnosis and rapid intraoperative and postoperative treatment allowed a favorable evolution. Management was based on the use of diuretics, fluid restriction, and hypertonic sodium solutions.

Third National Registry of Cardiac Rehabilitation Programs in Mexico (RENAPREC III-2022) / Tercer Registro Nacional de Programas de Rehabilitación Cardiaca en México (RENAPREC III-2022)

Abstract Introduction: In Mexico, cardiac rehabilitation (CR) as an interdisciplinary intervention with therapeutic impact in patients with heart disease is growing. There is the need to know actual conditions of CR in our country. Objectives: The objective of this National Registry is to follow-up those existing and new CR units in Mexico through the comparison between the two previous registries, RENAPREC-2009 and RENAPREC II-2015 studies. This is a descriptive study focused on diverse CR activities such as assistance training, and certification of health professionals, barriers, reference, population attended, interdisciplinarity, permanence over time, growth prospects, regulations, post-pandemic condition, integrative characteristics, and scientific research. Results: Data were collected from 45 CR centers in the 32 states, 75.5% are private practice units, 67% are new, 33% were part of RENAPREC II-2015, and 17 have continued since 2009. With a better distribution of CR units along the territory, the median reference of candidates for CR programs is 9% with a significant reduction into tiempo of enrollment to Phase II admission (19 ± 11 days). Regarding to previous registries, the coverance of Phases I, II, and III is 71%, 100%, and 93%, respectively; and a coverance increases in evaluation, risk stratification, and prescription, more comprehensive attendance and prevention strategies. Conclusions: CR in Mexico has grown in the past 7 years. Even there is still low reference and heterogeneity in specific processes, there are strengths such as interdisciplinarity, scientific professionalization of specialists, national diversification, and an official society that are consolidated over time.

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Corrigendum: Urine L-selectin reflects clinical and histological renal disease activity and treatment response in lupus nephritis across multi-ethnicity.

[This corrects the article DOI: 10.3389/fimmu.2023.1200167.].

Urine L-selectin reflects clinical and histological renal disease activity and treatment response in lupus nephritis across multi-ethnicity.

Objective: There is an urgent need for novel biomarkers in lupus nephritis (LN). We report a non-invasive urinary biomarker, L-selectin, in two independent multi-ethnic cohorts. Methods: uL-selectin was tested cross-sectionally in a Chinese cohort (n=255) and a US cohort (n=219) of SLE patients and controls using ELISA. A longitudinal cohort includes 20 active Chinese LN patients. Results: uL-selectin was significantly increased in active LN patients compared to active non-renal SLE, inactive LN, inactive non-renal SLE, chronic kidney disease patients, and healthy controls. uL-selectin positively correlated with global and renal disease activities as well as histological activity index and chronicity index (CI). Low uL-selectin was an independent predictor for high CI. During follow-up, uL-selectin levels decreased significantly in the complete renal remission group. Conclusion: uL-selectin is a novel biomarker of disease activity and renal histopathology in LN across multiple ethnicities. It also reflects treatment response in LN patients during follow up.

Integrated genomic, proteomic and cognitive assessment in Duchenne Muscular Dystrophy suggest astrocyte centric pathology.

Introduction: Documented Duchenne Muscular Dystrophy (DMD) biomarkers are confined to Caucasians and are poor indicators of cognitive difficulties and neuropsychological alterations. Materials and methods: This study correlates serum protein signatures with cognitive performance in DMD patients of South Asian origin. Study included 25 DMD patients aged 6-16 years. Cognitive profiles were assessed by Wechsler Intelligence Scale for Children. Serum proteome profiling of 1317 proteins was performed in eight DMD patients and eight age-matched healthy volunteers. Results: Among the several novel observations we report, better cognitive performance in DMD was associated with increased serum levels of MMP9 and FN1 but decreased Siglec-3, C4b, and C3b. Worse cognitive performance was associated with increased serum levels of LDH-H1 and PDGF-BB but reduced GDF-11, MMP12, TPSB2, and G1B. Secondly, better cognitive performance in Processing Speed (PSI) and Perceptual Reasoning (PRI) domains was associated with intact Dp116, Dp140, and Dp71 dystrophin isoforms while better performance in Verbal Comprehension (VCI) and Working Memory (WMI) domains was associated with intact Dp116 and Dp140 isoforms. Finally, functional pathways shared with Alzheimer's Disease (AD) point towards an astrocyte-centric model for DMD. Conclusion: Astrocytic dysfunction leading to synaptic dysfunction reported previously in AD may be a common pathogenic mechanism underlying both AD and DMD, linking protein alterations to cognitive impairment. This new insight may pave the path towards novel therapeutic approaches targeting reactive astrocytes.

[Third National Registry of Cardiac Rehabilitation Programs in Mexico (RENAPREC III-2022)]. / Tercer Registro Nacional de Programas de Rehabilitación Cardiaca en México (RENAPREC III-2022).

Introduction: In Mexico, cardiac rehabilitation (CR) as an interdisciplinary intervention with therapeutic impact in patients with heart disease is growing. There is the need to know actual conditions of CR in our country. Objectives: The objective of this National Registry is to follow-up those existing and new CR units in Mexico through the comparison between the two previous registries, RENAPREC-2009 and RENAPREC II-2015 studies. This is a descriptive study focused on diverse CR activities such as assistance training, and certification of health professionals, barriers, reference, population attended, interdisciplinarity, permanence over time, growth prospects, regulations, post-pandemic condition, integrative characteristics, and scientific research. Results: Data were collected from 45 CR centers in the 32 states, 75.5% are private practice units, 67% are new, 33% were part of RENAPREC II-2015, and 17 have continued since 2009. With a better distribution of CR units along the territory, the median reference of candidates for CR programs is 9% with a significant reduction into tiempo of enrollment to Phase II admission (19 ± 11 days). Regarding to previous registries, the coverance of Phases I, II, and III is 71%, 100%, and 93%, respectively; and a coverance increases in evaluation, risk stratification, and prescription, more comprehensive attendance and prevention strategies. Conclusions: CR in Mexico has grown in the past 7 years. Even there is still low reference and heterogeneity in specific processes, there are strengths such as interdisciplinarity, scientific professionalization of specialists, national diversification, and an official society that are consolidated over time.

Introducción: En México, la Rehabilitación Cardíaca (RC) como intervención interdisciplinaria con impacto terapéutico en paciente con cardiopatía está en crecimiento. Existe la necesidad de conocer las condiciones actuales de la RC en nuestro país. Objetivo: El objetivo de este Registro es dar seguimiento comparativo de las unidades nuevas y existentes entre los registros anteriores, RENAPREC-2009 y RENAPREC II-2015. Se trata de un estudio descriptivo centrado en diversas actividades de la RC: formación asistencial y certificación de sus profesionales, barreras, referencia, población atendida, interdisciplinariedad, permanencia en el tiempo, perspectivas de crecimiento, normativa, condición pospandemia, características integradoras e investigación. Resultados: Se recolectaron datos de 45 centros en los 32 estados, 67% son nuevos 75.5% son de práctica privada, 33% fueron parte de RENAPREC II-2015 y 17 desde 2009. Con una mejor distribución de las unidades de RC a lo largo del territorio, la mediana de referencia de pacientes candidatos a RC es ahora del 9% con reducción significativa del tiempo de admisión a Fase II (19 ± 11 días). Respecto a registros anteriores las coberturas de las Fases I, II y III son del 71%, 100% y 93%, respectivamente; con un aumento de la cobertura en evaluación, estratificación de riesgo y prescripción, atención más integral y estrategias de prevención. Conclusiones: La RC en México ha crecido en los últimos 7 años. Si bien aún existe baja referencia y heterogeneidad en procesos específicos, existen fortalezas como la interdisciplinariedad, la profesionalización científica de los especialistas, la diversificación nacional y una sociedad oficial que se consolida en el tiempo.

Quantitative proteomic screening uncovers candidate diagnostic and monitoring serum biomarkers of ankylosing spondylitis.

BACKGROUND: We sought to discover serum biomarkers of ankylosing spondylitis (AS) for diagnosis and monitoring disease activity. METHODS: We studied biologic-treatment-naïve AS and healthy control (HC) patients' sera. Eighty samples matched by age, gender, and race (1:1:1 ratio) for AS patients with active disease, inactive disease, and HC were analyzed with SOMAscan™, an aptamer-based discovery platform. T-tests tests were performed for high/low-disease activity AS patients versus HCs (diagnosis) and high versus low disease activity (Monitoring) in a 2:1 and 1:1 ratio, respectively, to identify differentially expressed proteins (DEPs). We used the Cytoscape Molecular Complex Detection (MCODE) plugin to find clusters in protein-protein interaction networks and Ingenuity Pathway Analysis (IPA) for upstream regulators. Lasso regression analysis was performed for diagnosis. RESULTS: Of the 1317 proteins detected in our diagnosis and monitoring analyses, 367 and 167 (317 and 59, FDR-corrected q < .05) DEPs, respectively, were detected. MCODE identified complement, IL-10 signaling, and immune/interleukin signaling as the top 3 diagnosis PPI clusters. Complement, extracellular matrix organization/proteoglycans, and MAPK/RAS signaling were the top 3 monitoring PPI clusters. IPA showed interleukin 23/17 (interleukin 22, interleukin 23A), TNF (TNF receptor-associated factor 3), cGAS-STING (cyclic GMP-AMP synthase, Stimulator of Interferon Gene 1), and Jak/Stat (Signal transducer and activator of transcription 1), signaling in predicted upstream regulators. Lasso regression identified a Diagnostic 13-protein model predictive of AS. This model had a sensitivity of 0.75, specificity of 0.90, a kappa of 0.59, and overall accuracy of 0.80 (95% CI: 0.61-0.92). The AS vs HC ROC curve was 0.79 (95% CI: 0.61-0.96). CONCLUSION: We identified multiple candidate AS diagnostic and disease activity monitoring serum biomarkers using a comprehensive proteomic screen. Enrichment analysis identified key pathways in AS diagnosis and monitoring. Lasso regression identified a multi-protein panel with modest predictive ability.

Comprehensive proteomics and platform validation of urinary biomarkers for bladder cancer diagnosis and staging.

BACKGROUND: Bladder cancer (BC) is among the most common cancers diagnosed in men in the USA. The current gold standards for the diagnosis of BC are invasive or lack the sensitivity to correctly identify the disease. METHODS: An aptamer-based screen analyzed the expression of 1317 proteins in BC compared to urology clinic controls. The top hits were subjected to systems biology analyses. Next, 30 urine proteins were ELISA-validated in an independent cohort of 68 subjects. Three of these proteins were next validated in an independent BC cohort of differing ethnicity. RESULTS: Systems biology analysis implicated molecular functions related to the extracellular matrix, collagen, integrin, heparin, and transmembrane tyrosine kinase signaling in BC susceptibility, with HNF4A and NFKB1 emerging as key molecular regulators. STEM analysis of the dysregulated pathways implicated a functional role for the immune system, complement, and interleukins in BC disease progression. Of 21 urine proteins that discriminated BC from urology clinic controls (UC), urine D-dimer displayed the highest accuracy (0.96) and sensitivity of 97%. Furthermore, 8 urine proteins significantly discriminated MIBC from NMIBC (AUC = 0.75-0.99), with IL-8 and IgA being the best performers. Urine IgA and fibronectin exhibited the highest specificity of 80% at fixed sensitivity for identifying advanced BC. CONCLUSIONS: Given the high sensitivity (97%) of urine D-dimer for BC, it may have a role in the initial diagnosis or detection of cancer recurrence. On the other hand, urine IL-8 and IgA may have the potential in identifying disease progression during patient follow-up. The use of these biomarkers for initial triage could have a significant impact as the current cystoscopy-based diagnostic and surveillance approach is costly and invasive when compared to a simple urine test.

Distinct gene dysregulation patterns herald precision medicine potentiality in systemic lupus erythematosus.

OBJECTIVES: We aimed at investigating the whole-blood transcriptome, expression quantitative trait loci (eQTLs), and levels of selected serological markers in patients with SLE versus healthy controls (HC) to gain insight into pathogenesis and identify drug targets. METHODS: We analyzed differentially expressed genes (DEGs) and dysregulated gene modules in a cohort of 350 SLE patients and 497 HC from the European PRECISESADS project (NTC02890121), split into a discovery (60%) and a replication (40%) set. Replicated DEGs qualified for eQTL, pathway enrichment, regulatory network, and druggability analysis. For validation purposes, a separate gene module analysis was performed in an independent cohort (GSE88887). RESULTS: Analysis of 521 replicated DEGs identified multiple enriched interferon signaling pathways through Reactome. Gene module analysis yielded 18 replicated gene modules in SLE patients, including 11 gene modules that were validated in GSE88887. Three distinct gene module clusters were defined i.e., "interferon/plasma cells", "inflammation", and "lymphocyte signaling". Predominant downregulation of the lymphocyte signaling cluster denoted renal activity. By contrast, upregulation of interferon-related genes indicated hematological activity and vasculitis. Druggability analysis revealed several potential drugs interfering with dysregulated genes within the "interferon" and "PLK1 signaling events" modules. STAT1 was identified as the chief regulator in the most enriched signaling molecule network. Drugs annotated to 15 DEGs associated with cis-eQTLs included bortezomib for its ability to modulate CTSL activity. Belimumab was annotated to TNFSF13B (BAFF) and daratumumab was annotated to CD38 among the remaining replicated DEGs. CONCLUSIONS: Modulation of interferon, STAT1, PLK1, B and plasma cell signatures showed promise as viable approaches to treat SLE, pointing to their importance in SLE pathogenesis.

Personal and Work-Related Burnout Is Associated with Elevated Diastolic Blood Pressure and Diastolic Hypertension among Working Adults in Chile.

We aimed at investigating the association of personal and work-related burnout with blood pressure and hypertension among working adults in Chile. We conducted a cross-sectional study among 1872 working adults attending the Hospital del Trabajador in Santiago, Chile, between September 2015 and February 2018. The Copenhagen Burnout Inventory was used to assess personal and work-related burnout. Blood pressure was measured by medical practitioners. Multivariable linear and logistic regressions were used to estimate the association of burnout status with systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension. After adjusting for confounders, participants with both types of burnout had a 1.66 (95% confidence interval [CI]: 0.02-3.30) mmHg higher mean DBP than those without burnout. The odds of isolated diastolic hypertension among the participants with only personal burnout and both types of burnout were 2.00-fold (odds ratio [OR] = 2.00; 95% CI: 1.21-3.31) and 2.08-fold (OR = 2.08; 95% CI: 1.15-3.78) higher than those without burnout. The odds of combined systolic/diastolic hypertension among the participants with only work-related burnout increased by 59% (OR = 1.59; 95% CI: 1.01-2.50) compared with those without burnout. Both work-related and personal burnouts were associated with increased DBP and odds of diastolic hypertension among working adults in Chile.

Urinary CD163 is a marker of active kidney disease in childhood-onset lupus nephritis.

OBJECTIVE: The objective of this study was to evaluate the utility of urine CD163 for detecting disease activity in childhood-onset SLE (cSLE) patients. METHODS: Sixty consecutive pediatric patients fulfilling four or more ACR criteria for SLE and 20 healthy controls were recruited for testing of urinary CD163 using ELISA. SLE disease activity was assessed using the SLEDAI-2K. RESULTS: Urine CD163 was significantly higher in patients with active LN than inactive SLE patients and healthy controls, with receiver operating characteristics area under the curve values ranging from 0.93 to 0.96. LN was ascertained by kidney biopsy. Levels of CD163 significantly correlated with the SLEDAI, renal SLEDAI, urinary protein excretion and C3 complement levels. Urine CD163 was also associated with high renal pathology activity index and chronicity index, correlating strongly with interstitial inflammation and interstitial fibrosis based on the examination of concurrent kidney biopsies. CONCLUSION: Urine CD163 emerges as a promising marker for identifying cSLE patients with active kidney disease. Longitudinal studies are warranted to validate the clinical utility of urine CD163 in tracking kidney disease activity in children with lupus.

Pain, mood, and suicidal behavior among injured working adults in Chile.

BACKGROUND: Chronic pain is comorbid with psychiatric disorders, but information on the association of chronic pain with depressive symptoms, generalized anxiety, and suicidal behavior among occupational cohorts is inadequate. We investigated these associations among employed Chilean adults. METHODS: A total of 1946 working adults were interviewed during their outpatient visit. Pain was assessed using the Short Form McGill Pain questionnaire (SF-MPG) while depression and generalized anxiety were examined using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. The Columbia-Suicide Severity Rating Scale was used to assess suicidal behavior and suicidal ideation. Multivariable logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (95%CI) for the association of chronic pain with mood disorders, as well as suicidal behavior. RESULTS: High chronic pain (SF-MPG > 11) was reported by 46% of participants. Approximately two-fifths of the study participants (38.2%) had depression, 23.8% generalized anxiety, 13.4% suicidal ideation, and 2.4% suicidal behavior. Compared to those with low pain (SF-MPG ≤11), participants with high chronic pain (SF-MPG > 11) had increased odds of experiencing depression only (aOR = 2.87; 95% CI: 2.21-3.73), generalized anxiety only (aOR = 2.38; 95% CI: 1.42-3.99), and comorbid depression and generalized anxiety (aOR = 6.91; 95% CI: 5.20-9.19). The corresponding aOR (95%CI) for suicidal ideation and suicidal behavior were (aOR = 2.20; 95% CI: 1.58-3.07) and (aOR = 2.18 = 95% CI: 0.99-4.79), respectively. CONCLUSIONS: Chronic pain is associated with increased odds of depression, generalized anxiety, and suicidal behavior. Mental health support and appropriate management of patients experiencing chronic pain are critical.

Oligoclonal M bands unveil occult inflammation in multiple sclerosis.

INTRODUCTION: Recent works demonstrate that patients with multiple sclerosis (pwMS) and oligoclonal M bands (OCMB) in cerebrospinal fluid (CSF) are at higher risk of conversion to secondary progressive course, suggesting a distinct pathophysiology pathway in these patients. OBJECTIVES: To analyze the relationship of serum neurofilament light chain (s-NFL) in absence of inflammatory activity in people with multiple sclerosis (pwMS) according to the presence of OCMB versus healthy controls (HC), and the effect of aging. METHODS: Two cohorts of HC were compared to a cohort of pwMS without clinical or radiological signs of acute inflammation. Lack of inflammation was defined as the absence of relapses or gadolinium-enhancing lesions (GEL) brain in an MRI performed within three months before and after s-NFL determination. S-NFL was measured with SIMOa technology. OCMB in the cerebrospinal fluid (CSF) were analyzed with isoelectric focusing and immunoblotting. RESULTS: 254 people were studied: 124 healthy voluntary controls and 130 pwMS. Despite the absence of inflammatory activity, pwMS and OCMB showed higher levels of s-NFL compared to those without OCMB and HC (11.4 pg/mL, 8.9 pg/mL and 9.0 pg/mL, respectively). A positive and exponential correlation between age and s-NFL was observed, with highest increases among pwMS and OCMB in the CSF. DISCUSSION: In absence of overt inflammatory activity, pwMS and OCMB exhibit higher s-NFL levels, and a greater age-related increase. Thus, OCMB may portray an underlying inflammatory process not detected by conventional MRI studies and may explain the poorer prognosis of these patients.

Case Report: Exacerbation of Relapses Following mRNA COVID-19 Vaccination in Multiple Sclerosis: A Case Series.

Introduction: mRNA coronavirus disease 2019 (COVID-19) vaccination has been widely used to arrest the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Rarely, autoimmune events such as relapses in patients with multiple sclerosis (MS) have been reported after vaccination. However, the possible effects of vaccination in a patient already experiencing the symptoms of a relapse represent an unusual scenario that has not been described. Patients and Methods: This is a retrospective case series of four patients from three major tertiary referral centers that received mRNA COVID-19 vaccination after starting with symptoms of acute demyelination of the central nervous system due to non-recognized MS. A detailed description of each case, including MRI studies, serum light-neurofilament levels, and cerebrospinal fluid (CSF) cytokine profile, is provided. Case Description: All patients presented exacerbation of ongoing symptoms after vaccination (range 14-112 days first dose). All patients presented MRI features suggestive of highly active MS and fulfilled McDonald 2017 criteria at the time of presentation. All patients presented high serum light-neurofilament levels and oligoclonal G bands restricted to the CSF. Higher levels of interleukin-6 in the CSF were present in the more severe cases. Discussion: We describe exacerbation of relapses after mRNA COVID-19 vaccination. We hypothesize RNA sensors such as Toll-like receptor 7 may be activated and contribute to amplify the inflammatory response during a relapse. Conclusion: Patients should seek medical attention if experiencing acute neurological symptoms, especially before vaccination. Fast diagnostic procedures and prompt treatment should be performed in these patients. Pharmacovigilance and further study are warranted to confirm causality.

Evaluating the performance of the Pain Interference Index and the Short Form McGill Pain Questionnaire among Chilean injured working adults.

BACKGROUND: Chronic pain can lead to economic instability, decreased job productivity, and poor mental health. Therefore, reliable identification and quantification of chronic pain is important for clinical diagnosis and treatment. OBJECTIVE: To determine the psychometric properties of the Spanish language versions of the Pain Interference Index (PII) and the Short Form McGill Pain Questionnaire (SF-MPG) among a population of working adults who experienced injury in Santiago, Chile. METHODS: A total of 1,975 participants with work-related injuries were interviewed to collect sociodemographic, occupational, and chronic pain characteristics. Construct validity and factorial structure of the PII and SF-MPG were assessed through exploratory factor analyses (EFA). Cronbach's alpha was used to evaluate internal consistency. RESULTS: The PII mean score was 3.84 ± 1.43 among all participants. The SF-MPG median score was 11 [IQR: 6-16] in this study population. Cronbach's alpha for the PII was 0.90 and 0.87 for the SF-MP. EFA resulted in a one factor solution for the PII. A two-factor solution was found for the SF-MPG. The two-factors for SF-MPG were sensory and affective subscales with Cronbach's alpha of 0.82 and 0.714, respectively. When the two scales were combined, an EFA analysis confirmed the PII and SF-MPG measure different aspects of chronic pain. CONCLUSIONS: The PII and SF-MPG had good construct validity and reliability for assessing different aspects of chronic pain among working Chilean adults.

Effectiveness of rituximab vs. ocrelizumab for the treatment of primary progressive multiple sclerosis: a real-world observational study.

INTRODUCTION: Ocrelizumab, an antiCD-20 antibody, is the only drug approved to treat patients with primary progressive multiple sclerosis (pwPPMS). Not all candidates receive this treatment due to prescription limitations. Rituximab, another antiCD-20 antibody, has been used off-label in pwPPMS before and after ocrelizumab approval. However, studies comparing effectiveness of both drugs are lacking. OBJECTIVE: To evaluate effectiveness of rituximab and ocrelizumab in pwPPMS under real-life conditions. METHODS: We conducted a multicentric observational study of pwPPMS that started ocrelizumab or rituximab according to clinical practice, with a minimum follow-up of 1 year. Data was collected prospectively and retrospectively. Primary outcome was time to confirmed disability progression at 3 months (CDW). Secondary outcome was serum neurofilament light chain levels (sNFL) at the end of follow-up. RESULTS: 95 out 111 pwPPMS fulfilled inclusion criteria and follow-up data availability: 49 (51.6%) received rituximab and 46 (48.4%) ocrelizumab. Rituximab-treated patients had significantly higher baseline EDSS, disease duration and history of previous disease-modifying treatment (DMT) than ocrelizumab-treated patients. After a mean follow-up of 18.3 months (SD 5.9), 26 patients experienced CDW (21.4%); 15 (30.6%) in the rituximab group; and 11 (23.9%) in the ocrelizumab group. Survival analysis revealed no differences in time to CDW. sNFL were measured in 60 patients and no differences between groups were found. INTERPRETATION: We provide real-world evidence of effectiveness of ocrelizumab and rituximab in pwPPMS. No differences in time to CDW were found between treatments. However, this study cannot establish equivalence of treatments and warrant clinical trial to confirm our findings.

Characteristics of patients in inpatient psychiatry during the COVID-19 pandemic.

To date, there have been limited publications examining the characteristics of psychiatric patients with COVID-19 in an inpatient setting. In this retrospective cohort review, we attempted to categorize the differences between patients admitted to the COVID unit versus the non-COVID unit using data from a community hospital located on Long Island, NY. We found that patients admitted to the COVID-19 unit had on average longer lengths of stay, were more likely to belong to non-white racial groups, and were less likely to be smokers.