Gastrointestinal dysmotility is associated with proton pump inhibitor refractory esophagitis in patients with systemic sclerosis.

OBJECTIVES: Patients with systemic sclerosis present with severe gastroesophageal reflux disease, often refractory to proton-pump inhibitors (PPI) treatment. The aim of the present study was to identify factors associated with PPI-refractory esophagitis. METHODS: We performed a cross-sectional study in a single-center cohort of patients diagnosed with systemic sclerosis. We included patients who underwent an esophagogastroduodenoscopy while on PPI treatment. Patients with PPI-refractory erosive esophagitis were compared with those with endoscopically normal esophageal mucosa. RESULTS: A total of 69 patients were included, from these, 23 patients (33%) had PPI-refractory esophagitis (Grade A, n = 11; Grade B, n = 7; Grade C, n = 2; Grade D, n = 3) and 46 (67%) had an endoscopically normal esophageal mucosa. On univariate analysis, patients with PPI-refractory esophagitis were more frequently diffuse SSc subset (43% vs 17%; p= 0.041). Evaluating gastrointestinal motility tests, neither absent esophageal contractility (39% vs 25%, p= 0.292) nor hypotensive lower esophageal sphincter (47% vs 44%, p= 0.980) were significantly associated with PPI-refractory esophagitis. Gastrointestinal dysmotility, defined as abnormal gastric emptying and/or small bowel dilated loops, was significantly associated with PPI-refractory esophagitis (66 vs 8%, p = <0.001). On a multivariate regression model to evaluate the association between motility test results adjusted for the diffuse subset, gastrointestinal dysmotility (ß = 0.751, p= 0.010) was independently associated with PPI-refractory esophagitis, while absent esophageal contractility (ß = 0.044, p= 0.886) or a hypotensive LES were not (ß=-0.131, p= 0.663). CONCLUSIONS: Our findings suggest that gastric and small intestinal motor dysfunction may be an important contributor to the development of PPI-refractory esophagitis in patients with systemic sclerosis.

Prevalence and prognostic implications of the no-reflux phenomenon in patients undergoing primary percutaneous coronary intervention at a university center in a middle-income country.

OBJECTIVE: To analyze the prevalence of no-reflow and the 30-day mortality in a university center in a middle-income country. METHOD: We analyzed 2463 patients who underwent primary PCI from January 2006 to December 2021. The outcome measure was 30-day mortality. RESULTS: Of a total of 2463 patients, no-reflow phenomenon was found in 413 (16.8%) patients, 30-day mortality was 16.7 vs. 4.29% (p < 0.001). Patients with no-reflow were older 60 (53-69.5) vs. 59 (51-66) (p = 0.001), with a higher delay in onset of symptom to emergency department arrival 270 vs. 247 min (p = 0.001). No-reflow patients also had had fewer previous myocardial infarction, 11.6 vs. 18.4 (p = 0.001) and a Killip class > 1, 37 vs. 26% (p < 0.001). No-reflow patients were more likely to have an anterior myocardial infarction (55.4 vs. 47.8%; p = 0.005) and initial TIMI flow 0 (76 vs. 68%; p < 0.001). CONCLUSION: No-reflow occurred in 16.8% of STEMI patients undergoing primary PCI and was more likely with older age, delayed presentation, anterior myocardial infarction and Killip class > 1. No-reflow was associated with a higher mortality at 30-day follow-up.

OBJETIVOS: Analizar la prevalencia de no reflujo y la mortalidad a 30 días en un centro universitario de un país de ingresos medios. MÉTODO: Analizamos 2,463 pacientes que se sometieron a ICP primaria desde enero de 2006 hasta diciembre de 2021. La medida de resultado fue la mortalidad a los 30 días. RESULTADOS: Del total de 2,463 pacientes, se encontró fenómeno de no reflujo en 413 (16.8%), la mortalidad a los 30 días fue del 16.7 vs. 4.29% (p < 0.001). Los pacientes sin reflujo tenían mayor edad 60 (53-69.5) vs. 59 (51-66) (p = 0.001), con mayor retraso del inicio de los síntomas a la llegada a urgencias, 270 vs. 247 min (p = 0.001). Los pacientes sin reflujo también tenían menos infarto de miocardio previo, 11.6 vs. 18.4 (p = 0.001), y una clase Killip > 1, 37 vs. 26% (p < 0.001). Los pacientes sin reflujo tenían más probabilidades de tener un infarto de miocardio anterior (55.4 vs. 47.8%; p = 0.005) y flujo TIMI inicial 0 (76 vs. 68%; p < 0.001). CONCLUSIÓN: Ocurrió ausencia de reflujo en el 16.8% de los pacientes con IAMCEST sometidos a ICP primaria y fue más probable con la edad avanzada, presentación tardía, infarto de miocardio anterior y clase Killip > 1. El no reflujo se asoció con una mayor mortalidad a los 30 días de seguimiento.

Pathological autoantibody internalisation in myositis.

OBJECTIVES: Autoantibodies targeting intracellular proteins are common in various autoimmune diseases. In the context of myositis, the pathologic significance of these autoantibodies has been questioned due to the assumption that autoantibodies cannot enter living muscle cells. This study aims to investigate the validity of this assumption. METHODS: Confocal immunofluorescence microscopy was employed to localise antibodies and other proteins of interest in myositis muscle biopsies. Bulk RNA sequencing was used to examine the transcriptomic profiles of 669 samples, including those from patients with myositis, disease controls and healthy controls. Additionally, antibodies from myositis patients were introduced into cultured myoblasts through electroporation, and their transcriptomic profiles were analysed using RNA sequencing. RESULTS: In patients with myositis autoantibodies, antibodies accumulated inside myofibres in the same subcellular compartment as the autoantigen. Bulk RNA sequencing revealed that muscle biopsies from patients with autoantibodies targeting transcriptional regulators exhibited transcriptomic patterns consistent with dysfunction of the autoantigen. For instance, in muscle biopsies from patients with anti-PM/Scl autoantibodies recognising components of the nuclear RNA exosome complex, an accumulation of divergent transcripts and long non-coding RNAs was observed; these RNA forms are typically degraded by the nuclear RNA exosome complex. Introducing patient antibodies into cultured muscle cells recapitulated the transcriptomic effects observed in human disease. Further supporting evidence suggested that myositis autoantibodies recognising other autoantigens may also disrupt the function of their targets. CONCLUSIONS: This study demonstrates that, in myositis, autoantibodies are internalised into living cells, causing biological effects consistent with the disrupted function of their autoantigen.

Prognostic value of anti-IFI16 autoantibodies in pulmonary arterial hypertension and mortality in patients with systemic sclerosis / Valor pronóstico de los autoanticuerpos anti-IFI16 en la hipertensión arterial pulmonar y en la mortalidad en los pacientes con esclerodermia sistémica

Objectives: To determine the diagnostic value of anti-interferon gamma inducible protein 16 (IFI16) autoantibodies in systemic sclerosis (SSc) patients negative for all tested SSc-specific autoantibodies (SSc-seronegative patients) and to evaluate the clinical significance of these autoantibodies, whether isolated or in the presence of anti-centromere autoantibodies (ACA). Methods: Overall, 58 SSc-seronegative and 66 ACA-positive patients were included in the study. All patients were tested for anti-IFI16 autoantibodies by an in-house direct ELISA. Associations between clinical parameters and anti-IFI16 autoantibodies were analysed. Results: Overall, 17.2% of SSc-seronegative and 39.4% of ACA-positive patients were positive for anti-IFI16 autoantibodies. Anti-IFI16 autoantibodies were found only in patients within the limited cutaneous SSc (lcSSc) subset. A positive association between anti-IFI16 positivity and isolated pulmonary arterial hypertension (PAH) was found (odds ratio [OR]=5.07; p=0.014) even after adjusting for ACA status (OR=4.99; p=0.019). Anti-IFI16-positive patients were found to have poorer overall survival than negative patients (p=0.032). Cumulative survival rates at 10, 20 and 30 years were 96.9%, 92.5% and 68.7% for anti-IFI16-positive patients vs. 98.8%, 97.0% and 90.3% for anti-IFI16-negative-patients, respectively. Anti-IFI16-positive patients also had worse overall survival than anti-IFI16-negative patients after adjusting for ACA status in the multivariate Cox analysis (hazard ratio [HR]=3.21; p=0.043). Conclusion: Anti-IFI16 autoantibodies were associated with isolated PAH and poorer overall survival. Anti-IFI16 autoantibodies could be used as a supplementary marker of lcSSc in SSc-seronegative patients and for identifying ACA-positive patients with worse clinical outcome. (AU)

Objetivos: Determinar el valor diagnóstico de los autoanticuerpos anti-interferon gamma inducible protein 16 (IFI16) en los pacientes con esclerodermia sistémica (SSc) negativos para todos los autoanticuerpos específicos de SSc (pacientes SSc seronegativos) y evaluar el significado clínico de estos autoanticuerpos, aislados o en combinación con autoanticuerpos anticentrómero (ACA). Métodos: Se incluyeron 58 pacientes SSc seronegativos y 66 pacientes ACA positivos. Todos los pacientes se testaron para los autoanticuerpos anti-IFI16 mediante un ELISA directo «in-house». Las asociaciones entre parámetros clínicos y los autoanticuerpos anti-IFI16 fueron analizadas. Resultados: En total, el 17,2% de los pacientes SSc seronegativos y el 39,4% de los pacientes ACA positivos fueron positivos para anti-IFI16. Los autoanticuerpos anti-IFI16 se detectaron solamente en los pacientes con la forma limitada cutánea de SSc (lcSSc). Se encontró una asociación entre la positividad de anti-IFI16 y la hipertensión arterial pulmonar (HAP) aislada (odds ratio [OR]: 5,07; p=0,014), incluso cuando se ajustó el análisis a la presencia o ausencia de ACA (OR: 4,99; p=0,019). Los pacientes anti-IFI16 positivos mostraron una peor supervivencia general que los pacientes negativos (p=0,032). Las ratios de supervivencia acumulada a 10, 20 y 30 años fueron respectivamente del 96,9, 92,5 y 68,7% para los pacientes anti-IFI16 positivos frente al 98,8, 97,0 y 90,3% para los anti-IFI16 negativos. Los pacientes anti-IFI16 positivos también tenían una supervivencia general menor que los pacientes anti-IFI16 negativos tras ajustar para la presencia o ausencia de ACA mediante análisis multivariado de Cox (hazard ratio [HR]: 3,21; p=0,043)... (AU)

Nailfold capillaroscopy findings of a multicentric multi-ethnic cohort of patients with idiopathic inflammatory myopathies.

OBJECTIVES: To assess nailfold video capillaroscopic (NVC) abnormalities and their association with clinical features, myositis-specific autoantibodies (MSA), and myositis-associated antibodies (MAA) in a large multi-ethnic cohort of patients with idiopathic inflammatory myopathies (IIM). METHODS: We recruited 155 IIM patients from three centres in Mexico, Spain, and the USA. We evaluated the clinical and laboratory features of the patients and performed semiquantitative and quantitative analyses of the NVC. Each NVC study was defined as having a normal, non-specific, early systemic sclerosis (SSc), active SSc, or late SSc pattern. Twenty-three patients had at least one follow-up NVC when disease control was achieved. Quantitative variables were expressed as medians and interquartile range (IQR) and were compared with the Kruskal-Wallis, the Mann-Whitney U-test, and the Wilcoxon test for paired medians. Associations between qualitative variables were assessed with the χ2 test. RESULTS: Most patients were women (68.3%), Hispanic (73.5%), and had dermatomyositis (DM) (61.2%). Fourteen patients (9%) had a normal NVC. A non-specific abnormality pattern was the most frequent (53.9%), and was associated with joint involvement, interstitial lung disease, Jo1 autoantibodies, anti-synthetase syndrome, and immune-mediated necrotising myopathy. The SSc pattern was observed mostly in DM and overlap myositis and was associated with cutaneous features and anti-TIF-1g autoantibodies. After treatment, there was a decrease in the capillaroscopic score, the capillary diameter, and the number of avascular areas, and an increase in capillary density and bushy capillary number. CONCLUSIONS: NVC abnormalities are related to the diagnosis, clinical features, disease activity, and autoantibodies of patients with IIM.

Prognostic value of anti-IFI16 autoantibodies in pulmonary arterial hypertension and mortality in patients with systemic sclerosis.

OBJECTIVES: To determine the diagnostic value of anti-interferon gamma inducible protein 16 (IFI16) autoantibodies in systemic sclerosis (SSc) patients negative for all tested SSc-specific autoantibodies (SSc-seronegative patients) and to evaluate the clinical significance of these autoantibodies, whether isolated or in the presence of anti-centromere autoantibodies (ACA). METHODS: Overall, 58 SSc-seronegative and 66 ACA-positive patients were included in the study. All patients were tested for anti-IFI16 autoantibodies by an in-house direct ELISA. Associations between clinical parameters and anti-IFI16 autoantibodies were analysed. RESULTS: Overall, 17.2% of SSc-seronegative and 39.4% of ACA-positive patients were positive for anti-IFI16 autoantibodies. Anti-IFI16 autoantibodies were found only in patients within the limited cutaneous SSc (lcSSc) subset. A positive association between anti-IFI16 positivity and isolated pulmonary arterial hypertension (PAH) was found (odds ratio [OR]=5.07; p=0.014) even after adjusting for ACA status (OR=4.99; p=0.019). Anti-IFI16-positive patients were found to have poorer overall survival than negative patients (p=0.032). Cumulative survival rates at 10, 20 and 30 years were 96.9%, 92.5% and 68.7% for anti-IFI16-positive patients vs. 98.8%, 97.0% and 90.3% for anti-IFI16-negative-patients, respectively. Anti-IFI16-positive patients also had worse overall survival than anti-IFI16-negative patients after adjusting for ACA status in the multivariate Cox analysis (hazard ratio [HR]=3.21; p=0.043). CONCLUSION: Anti-IFI16 autoantibodies were associated with isolated PAH and poorer overall survival. Anti-IFI16 autoantibodies could be used as a supplementary marker of lcSSc in SSc-seronegative patients and for identifying ACA-positive patients with worse clinical outcome.

Long-Term Outcomes of Pharmacoinvasive Strategy Versus Primary Percutaneous Coronary Intervention in ST-Elevation Myocardial Infarction: A Study from Mexico City.

Although primary percutaneous coronary intervention (pPCI) is the treatment of choice in ST-elevation myocardial infarction (STEMI), challenges may arise in accessing this intervention for certain geodemographic groups. Pharmacoinvasive strategy (PIs) has demonstrated comparable outcomes when delays in pPCI are anticipated, but real-world data on long-term outcomes are limited. The aim of the present study was to compare long-term outcomes among real-world patients with STEMI who underwent either PIs or pPCI. This was a prospective registry including patients with STEMI who received reperfusion during the first 12 hours from symptom onset. The primary objective was cardiovascular mortality at 12 months according to the reperfusion strategy (pPCI vs PIs) and major cardiovascular events (cardiogenic shock, recurrent myocardial infarction, and congestive heart failure), and Bleeding Academic Research Consortium type 3 to 5 bleeding events were also evaluated. A total of 799 patients with STEMI were included; 49.1% underwent pPCI and 50.9% received PIs. Patients in the PIs group presented with more heart failure on admission (Killip-Kimbal >I 48.1 vs 39.7, p = 0.02) and had a lower proportion of pre-existing heart failure (0.2% vs 1.8%, p = 0.02) and atrial fibrillation (0.25% vs 1.2%, p = 0.02). No statistically significant difference was observed in cardiovascular mortality at the 12-month follow-up (hazard ratio for PIs 0.74, 95% confidence interval 0.42 to 1.30, log-rank p = 0.30) according to the reperfusion strategy used. The composite of major cardiovascular events (hazard ratio for PIs 0.98, 95% confidence interval 0.75 to 1.29, p = 0.92) and Bleeding Academic Research Consortium type 3 to 5 bleeding rates were also comparable. A low socioeconomic status, Killip-Kimball >2, age >60 years, and admission creatinine >2.0 mg/100 ml were predictors of the composite end point after multivariate analysis. In conclusion, this prospective real-world registry provides additional support that long-term major cardiovascular outcomes and bleeding are not different between patients who underwent PIs versus primary PCI.

Pathogenic autoantibody internalization in myositis.

Objectives: Myositis is a heterogeneous family of autoimmune muscle diseases. As myositis autoantibodies recognize intracellular proteins, their role in disease pathogenesis has been unclear. This study aimed to determine whether myositis autoantibodies reach their autoantigen targets within muscle cells and disrupt the normal function of these proteins. Methods: Confocal immunofluorescence microscopy was used to localize antibodies and other proteins of interest in myositis muscle biopsies. Bulk RNA sequencing was used to study the transcriptomic profiles of 668 samples from patients with myositis, disease controls, and healthy controls. Antibodies from myositis patients were introduced into cultured myoblasts by electroporation and the transcriptomic profiles of the treated myoblasts were studied by bulk RNA sequencing. Results: In patients with myositis autoantibodies, antibodies accumulated inside myofibers in the same subcellular compartment as the autoantigen. Each autoantibody was associated with effects consistent with dysfunction of its autoantigen, such as the derepression of genes normally repressed by Mi2/NuRD in patients with anti-Mi2 autoantibodies, the accumulation of RNAs degraded by the nuclear RNA exosome complex in patients with anti-PM/Scl autoantibodies targeting this complex, and the accumulation of lipids within myofibers of anti-HMGCR-positive patients. Internalization of patient immunoglobulin into cultured myoblasts recapitulated the transcriptomic phenotypes observed in human disease, including the derepression of Mi2/NuRD-regulated genes in anti-Mi2-positive dermatomyositis and the increased expression of genes normally degraded by the nuclear RNA exosome complex in anti-PM/Scl-positive myositis. Conclusions: In myositis, autoantibodies are internalized into muscle fibers, disrupt the biological function of their autoantigen, and mediate the pathophysiology of the disease.

Does the Impact of COVID-19 on Patients With Systemic Sclerosis Change Over Time?

OBJECTIVE: The outcome of patients with COVID-19 improved over the pandemic, including patients with systemic rheumatic diseases. However, data on patients with systemic sclerosis (SSc) are lacking. This study aimed to assess the outcome of patients with both SSc and COVID-19 over several waves. METHODS: Patients with both SSc and COVID-19 who were registered in the European Scleroderma Trials and Research group (EUSTAR) were collected between April 2020 and April 2021. Patients were assigned to waves 1, 2, or 3 depending on the date of their COVID-19 diagnosis. Primary endpoints were death, intensive care unit stay, or ventilatory support (severe outcome). Subgroup analyses of patients who were hospitalized or died were conducted. General and SSc-specific characteristics and treatment were compared over the waves. Descriptive statistics and multivariate logistic regression were applied. RESULTS: A total of 333 patients were included; 57 patients (17%) had a severe outcome, and 30 patients (9%) died. Compared to wave 1, significantly fewer patients with SSc suffered from severe COVID-19 in waves 2 and 3 (28.2% vs 9.8% and 12.7%; P < 0.001), fewer patients required hospitalization (46.7% vs 19.6% and 25.5%; P < 0.001) or ventilatory support (24.0% vs 8.7% and 10.9%; P = 0.001), and fewer patients died (15.7% vs 5.0% and 7.5%; P = 0.011). Patients were significantly younger, more often men, had less frequent arterial hypertension, and less SSc cardiac involvement over waves 1 to 3. Patients received significantly less medium to high doses of corticosteroids as they did SSc treatment. CONCLUSION: The outcome of patients with both SSc and COVID-19 improved significantly over time because of intrinsic and extrinsic factors.

Contribution of Telomere Length to Systemic Sclerosis Onset: A Mendelian Randomization Study.

Although previous studies have suggested a relationship between telomere shortening and systemic sclerosis (SSc), the association between these two traits remains poorly understood. The objective of this study was to assess the causal relationship between telomere length in leukocytes (LTL) and SSc using the two-sample Mendelian randomization approach, with the genome-wide association study data for both LTL and SSc. The results of inverse-variance weighted regression (OR = 0.716 [95% CI 0.528-0.970], p = 0.031) and the Mendelian randomization pleiotropy residual sum and outlier method (OR = 0.716 [95% CI 0.563-0.911], p = 0.035) indicate an association between telomere length and SSc. Specifically, longer genetically predicted LTL is associated with a reduced risk of SSc. Sensitivity tests highlight the significant roles of the variants rs10936599 and rs2736100 annotated to the TERC and TERT genes, respectively. Our findings suggest an influence of telomere length in leukocytes on the development of SSc.

Analysis of immortal-time effect in post-infarction ventricular septal defect.

Introduction: Time-fixed analyses have traditionally been utilized to examine outcomes in post-infarction ventricular septal defect (VSD). The aims of this study were to: (1) analyze the relationship between VSD closure/non-closure and mortality; (2) assess the presence of immortal-time bias. Material and methods: In this retrospective cohort study, patients with ST-elevation myocardial infarction (STEMI) complicated by VSD. Time-fixed and time-dependent Cox regression methodologies were employed. Results: The study included 80 patients: surgical closure (n = 26), transcatheter closure (n = 20), or conservative management alone (n = 34). At presentation, patients without VSD closure exhibited high-risk clinical characteristics, had the shortest median time intervals from STEMI onset to VSD development (4.0, 4.0, and 2.0 days, respectively; P = 0.03) and from STEMI symptom onset to hospital arrival (6.0, 5.0, and 0.8 days, respectively; P < 0.0001). The median time from STEMI onset to closure was 22.0 days (P = 0.14). In-hospital mortality rate was higher among patients who did not undergo defect closure (50%, 35%, and 88.2%, respectively; P < 0.0001). Closure of the defect using a fixed-time method was associated with lower in-hospital mortality (HR = 0.13, 95% CI 0.05-0.31, P < 0.0001, and HR 0.13, 95% CI 0.04-0.36, P < 0.0001, for surgery and transcatheter closure, respectively). However, when employing a time-varying method, this association was not observed (HR = 0.95, 95% CI 0.45-1.98, P = 0.90, and HR 0.88, 95% CI 0.41-1.87, P = 0.74, for surgery and transcatheter closure, respectively). These findings suggest the presence of an immortal-time bias. Conclusions: This study highlights that using a fixed-time analytic approach in post-infarction VSD can result in immortal-time bias. Researchers should consider employing time-dependent methodologies.

Real-World Evaluation of a Pharmacoinvasive Strategy for STEMI in Latin America: A Cost-Effective Approach with Short-Term Benefits.

Purpose: While pharmacoinvasive strategy (PI) is a safe and effective approach whenever access to primary percutaneous intervention (pPCI) is limited, data on each strategy's economic cost and impact on in-hospital stay are scarce. The objective is to compare the cost-effectiveness of a PI with that of pPCI for the treatment of ST-elevation myocardial infarction (STEMI) in a Latin-American country. Patients and Methods: A total of 1747 patients were included, of whom 470 (26.9%) received PI, 433 (24.7%) pPCI, and 844 (48.3%) NR. The study's primary outcome was the incremental cost-effectiveness ratio (ICER) for PI compared with those for pPCI and non-reperfused (NR), calculated for 30-day major cardiovascular events (MACE), 30-day mortality, and length of stay. Results: For PI, the ICER estimates for MACE showed a decrease of $-35.81/per 1% (95 confidence interval, -114.73 to 64.81) compared with pPCI and a decrease of $-271.60/per 1% (95% CI, -1086.10 to -144.93) compared with NR. Also, in mortality, PI had an ICER decrease of $-129.50 (95% CI, -810.57, 455.06) compared to pPCI and $-165.27 (-224.06, -123.52) with NR. Finally, length of stay had an ICER reduction of -765.99 (-4020.68, 3141.65) and -283.40 (-304.95, -252.76) compared to pPCI and NR, respectively. Conclusion: The findings of this study suggest that PI may be a more efficient treatment approach for STEMI in regions where access to pPCI is limited or where patient and system delays are expected.

[Acute myocardial infarction patients without COVID-19 manifestations in the pandemic may have high thrombus burden]. / Pacientes con infarto agudo de miocardio sin manifestaciones de COVID-19 pueden tener alta carga de trombo.

Objective: The objective of the study is to identify clinical and angiographic characteristics of patients with ST-segment elevation myocardial infarction (STEMI) but without clinical manifestations of COVID-19 infection during the pandemic, compared with patients 1 year before the pandemic. Methods: Observational study that included 138 consecutive patients hospitalized with STEMI who underwent primary percutaneous coronary intervention (PCI) without COVID-19 infection during the 2020 pandemic. A group of 175 STEMI patients treated with PCI in the year before the pandemic served as the control group. Results: During the periods analyzed, compared with the control group, patients admitted during the pandemic without clinical manifestations of COVID-19 did not have significant differences in demographic characteristics, comorbidities, or delayed time and location of the acute myocardial infarction. Furthermore, there were no differences between the two groups concerning levels of CK-MB and NT-proBNP, or in inflammation markers and left ventricular ejection fraction. In patients without COVID-19 during the pandemic compared with control, we found a higher intracoronary thrombus burden (thrombus grade 5; 78.3% vs. 62.9%, respectively. p = 0.002). Accordingly, the use of glycoprotein IIB/IIIa inhibitors (37.7% vs. 26.3%, p = 0.03) was higher in these patients. Conclusions: This study demonstrates an increased thrombus burden in STEMI patients without clinical manifestation of COVID-19 during the pandemic compared with the same time period in the previous year.

Objetivo: Identificar las características clínicas y angiográficas de los pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST) sin manifestaciones clínicas de COVID-19 durante la pandemia y compararlos con los pacientes en el año previo. Métodos: Estudio observacional que incluyó 138 pacientes consecutivos que fueron hospitalizados por IAMCEST y que fueron tratados con angioplastía primaria (ACTP) sin manifestaciones clínicas de COVID-19 durante la pandemia de 2020. Se seleccionó a un grupo control de 175 pacientes con IAMCEST tratados con ACTP en el año previo a la pandemia. Resultados: Los pacientes atendidos durante la pandemia no tuvieron diferencias significativas en cuanto a las características clínicas, demográficas, comorbilidades, tiempo de retraso y localización del infarto. Además, no hubo diferencias entre ambos grupos en los niveles de CK-MB, NT-proBNP, marcadores de inflamación ni en la fracción de eyección del ventrículo izquierdo. En los pacientes sin COVID-19 tratados durante la pandemia encontramos mayor carga trombótica intracoronaria (trombo grado 5; 78.3% vs. 62.9%, respectivamente. p = 0.002). De igual manera, el uso de inhibidores de la glucoproteina IIB/IIIa (37.7% vs. 26.3%, p = 0.03) fue mayor. Conclusiones: Este studio demostró un aumento en la carga trombótica en los pacientes con IAMCEST sin manifestaciones clínicas de COVID-19 durante la pandemia al compararlos con los pacientes tratados por la misma patología en el año previo.

Anti-nuclear valosin-containing protein-like autoantibody is associated with calcinosis and higher risk of cancer in systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc)-specific autoantibodies allow the diagnosis and predict the prognosis of SSc patients with different clinical characteristics. The aim of this study was to describe new SSc-related autoantibodies by a novel protein immunoprecipitation (IP) assay. METHODS: Serum samples and clinical data were collected from 307 SSc patients. Antinuclear autoantibodies were tested in all patients by indirect immunofluorescence (IIF) on HEp-2 cells. SSc-specific autoantibodies were evaluated with a commercial immunoblot and chemiluminescence immunoassay, and traditional RNA-IP. Patients negative for all these autoantibodies (n = 51) were further tested with a non-radioactive protein IP assay. Protein bands detected on SDS-PAGE were then analysed by mass spectrometry (MS) and confirmed by western blot (WB). Additional 56 patients with nucleolar pattern by IIF were tested by protein IP-WB. RESULTS: Five patients who underwent protein IP testing showed a 110-115kDa molecular weight band on SDS-PAGE and a homogeneous nucleolar pattern by IIF. MS identified the bands as nuclear valosin-containing protein-like (NVL). An additional positive patient was detected by IP-WB. As compared with the remaining 101 negative patients, anti-NVL positive patients showed a greater prevalence of calcinosis (100% vs 18.9%, p< 0.001), and cancer (66.7% vs 8.9%, p= 0.002), with a particular association with synchronous cancer (OR = 16.3; p= 0.024). CONCLUSION: We identified NVL as a new autoantibody target by a novel protein IP assay in SSc patients with a homogeneous nucleolar IIF pattern, testing negative for all known SSc-specific autoantibodies by commercial assays and RNA IP. Anti-NVL identifies a new clinical phenotype, characterized by calcinosis and cancer.

Nailfold videocapillaroscopy patterns in systemic sclerosis: implications for cutaneous subsets, disease features and prognostic value for survival.

OBJECTIVES: To assess the associations and prognostic value of scleroderma patterns by nailfold videocapillaroscopy (NVC) in patients with systemic sclerosis (SSc) and cutaneous subsets. METHODS: At baseline, 1356 SSc patients from the RESCLE registry were compared according to the scleroderma pattern as Late pattern and non-Late pattern, which included Early and Active patterns. Patient characteristics, disease features, survival time and causes of death were analysed. RESULTS: Late pattern was identified in 540 (39.8%), and non-Late pattern in 816 (60.2%) patients (88% women; 987 lcSSc/251 dcSSc). Late pattern was associated to dcSSc (OR=1.96; p<0.001), interstitial lung disease (ILD) (OR=1.29; p=0.031), and scleroderma renal crisis (OR=3.46; p<0.001). Once the cutaneous subset was disregarded in an alternative analysis, both digital ulcers (DU) (OR=1.29; p<0.037) and anti-topoisomerase I antibodies (OR=1.39; p< 0.036) emerged associated with the Late pattern. By cutaneous subsets, associations with Late pattern were: (1) in dcSSc, acro-osteolysis (OR=2.13; p=0.022), and systolic pulmonary artery pressure >40 mmHg by Doppler echocardiogram (OR=2.24; p<0.001); and (2) in lcSSc, ILD (OR=1.38; p=0.028). Survival was reduced in dcSSc with Late pattern compared to non-Late pattern (p=0.049). Risk factors for SSc mortality in multivariate regression Cox analysis were age at diagnosis (HR=1.03; p<0.001), dcSSc (HR=2.48; p<0.001), DU (HR=1.38; p=0.046), ILD (HR=2.81; p<0.001), and pulmonary arterial hypertension (HR=1.99; p<0.001). CONCLUSIONS: SSc patients with Late pattern more frequently present dcSSc and develop more fibrotic and vascular manifestations. Advanced microangiopathy by NVC identifies dcSSc patients at risk of reduced survival due to SSc-related causes.

External clinical validation of automated software to identify structural abnormalities and microhaemorrhages in nailfold videocapillaroscopy images.

OBJECTIVES: Automated systems to analyse nailfold videocapillaroscopy (NVC) images are needed to promptly and comprehensively characterise patients with systemic sclerosis (SSc) or Raynaud's phenomenon (RP). We previously developed, and validated in-house, a deep convolutional neural network-based algorithm to classify NVC-captured images according to the presence/absence of structural abnormalities and/or microhaemorrhages. We present its external clinical validation. METHODS: A total of 1,164 NVC images of RP patients were annotated by 5 trained capillaroscopists according to the following categories: normal capillary; dilation; giant capillary; abnormal shape; tortuosity; microhaemorrhage. The images were also presented to the algorithm. Matches and discrepancies between algorithm predictions and those annotations obtained by consensus of ≥3 or ≥4 interobservers were analysed. RESULTS: Consensus among ≥3 capillaroscopists was achieved in 86.9% of images, 75.8% of which were correctly predicted by the algorithm. Consensus among ≥4 experts occurred in 52.0% of cases, in which 87.1% of the algorithm's results matched with those of the expert panel. The algorithm's positive predictive value was >80% for microhaemorrhages and unaltered, giant or abnormal capillaries. Sensitivity was >75% for dilations and tortuosities. Negative predictive value and specificity were >89% for all categories. CONCLUSIONS: This external clinical validation suggests that this algorithm is useful to assist in the diagnosis and follow-up of SSc or RP patients in a timely manner. It may also be helpful in the management of patients with any pathology presenting with microvascular changes, as the algorithm has been designed to also be useful for research aiming at extending the usage of nailfold capillaroscopy to more conditions.