Evaluating remission and low disease activity from the perspective of the patient with axial spondyloarthritis: The cross-sectional ConREspAx study.

OBJECTIVES: To evaluate the properties of a single question to determine patient perception of remission and disease activity; to compare this with existing definitions for remission and low disease activity (LDA). METHODS: Single-center, cross-sectional study in a tertiary care hospital. Patients with axSpA (fulfilling ASAS criteria) were consecutively included. Both the patient's perception of remission and LDA and that of the physician were evaluated with a single question. Agreement between the patients' perception and other current definitions was tested using the prevalence-adjusted and bias-adjusted kappa (PABAK). The sensitivity (S) and specificity (Sp) of current definitions of disease states were tested against the patient's perception as the gold standard. RESULTS: The study population included 105 axSpA patients (63.8% males; 67.6% with radiographic sacroiliitis). Patients considered themselves to be in remission in 21% of cases and in LDA in 51.4%; physicians considered patients to be in remission in 45.7% of cases and in LDA in 35.2%. The poorest agreement was recorded for the patient's and the physician's perception of remission. The best agreement for patients' perception of remission was for a BASDAI < 2 and normal C-reactive protein values. This definition was also the most sensitive (S=72.7%) and specific (Sp=83.1%) when the patient's perception was taken as the gold standard. CONCLUSION: In a real-life setting, the evaluation of remission by the patient through a single question was the hardest criterion to achieve, although it did prove to be a feasible, valid, and specific way to assess remission.

Progressive multifocal leukoencephalopathy, advanced ductal breast carcinoma, systemic sclerosis, and checkpoint inhibitors: a therapeutic dilemma.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating central nervous system disease infection by JC virus (JCV) in patients with a significant decline in cellular immunity. No specific treatment has demonstrated efficacy, and the disease progresses to death in most patients. Recent findings have shown stabilization or improvement of PML lesions after treatment with checkpoint inhibitors (CPI) based on immune reconstitution. Nevertheless, immunotherapy may specifically cause autoimmune diseases or may deteriorate pre-existing ones. We report a case of a patient under treatment for advanced ductal breast carcinoma and systemic sclerosis, who developed PML. The therapeutic approach included withdrawal of drugs with possible immunosuppressive effect and treatment with pembrolizumab. In the absence of reliable markers to predict CPIs response and a concern for an autoimmune worsening, immunotherapy was administered late in the course of the disease. Finally, she did not experience an autoimmune disease flare-up; however, pembrolizumab could not prevent disease progression. We believe that potential autoimmune complications should not delay treatment initiation with CPIs in PML.

Stratification in systemic sclerosis according to autoantibody status versus skin involvement: a study of the prospective EUSTAR cohort.

BACKGROUND: The current subclassification of systemic sclerosis into cutaneous subtypes does not fully capture the heterogeneity of the disease. We aimed to compare the performances of stratification into LeRoy's cutaneous subtypes versus stratification by autoantibody status in systemic sclerosis. METHODS: For this cohort study, we assessed people with systemic sclerosis in the multicentre international European Scleroderma Trials and Research (EUSTAR) database. Individuals positive for systemic-sclerosis autoantibodies of two specificities were excluded, and remaining individuals were classified by cutaneous subtype, according to their systemic sclerosis-specific autoantibodies, or both. We assessed the performance of each model to predict overall survival, progression-free survival, disease progression, and different organ involvement. The three models were compared by use of the area under the curve (AUC) of the receiver operating characteristic and the net reclassification improvement (NRI). Missing data were imputed. FINDINGS: We assessed the database on July 26, 2019. Of 16 939 patients assessed for eligibility, 10 711 patients were included: 1647 (15·4%) of 10 709 were male, 9062 (84·6%) were female, mean age was 54·4 (SD 13·8) years, and mean disease duration was 7·9 (SD 8·2) years. Information regarding cutaneous subtype was available for 10 176 participants and antibody data were available for 9643 participants. In the prognostic analysis, there was no difference in AUC for overall survival (0·82, 95% CI 0·81-0·84 for cutaneous only vs 0·84, 0·82-0·85 for antibody only vs 0·84, 0·83-0·86 for combined) or for progression-free survival (0·70, 0·69-0·71 vs 0·71, 0·70-0·72 vs 0·71, 0·70-0·72). However, at 4 years the NRI showed substantial improvement for the antibody-only model compared with the cutaneous-only model in prediction of overall survival (0·57, 0·46-0·71 for antibody only vs 0·29, 0·19-0·39 for cutaneous only) and disease progression (0·36, 0·29-0·46 vs 0·21, 0·14-0·28). The antibody-only model did better than the cutaneous-only model in predicting renal crisis (AUC 0·72, 0·70-0·74 for antibody only vs 0·66, 0·64-0·69 for cutaneous only) and lung fibrosis leading to restrictive lung function (AUC 0·76, 0·75-0·77 vs 0·71, 0·70-0·72). The combined model improved the prediction of digital ulcers and elevated systolic pulmonary artery pressure, but did poorly for cardiac involvement. INTERPRETATION: The autoantibody-only model outperforms cutaneous-only subsetting for risk stratifying people with systemic sclerosis in the EUSTAR cohort. Physicians should be aware of these findings at the time of decision making for patient management. FUNDING: World Scleroderma Foundation.

Risk of Severe COVID-19 Infection in Patients With Inflammatory Rheumatic Diseases.

OBJECTIVE: To describe the cohort of patients with inflammatory rheumatic diseases (IRD) hospitalized due to SARS-CoV-2 infection in the Ramón y Cajal Hospital, and to determine the increased risk of severe coronavirus disease 2019 (COVID-19) in patients with no IRD. METHODS: This is a retrospective single-center observational study of patients with IRD actively monitored in the Department of Rheumatology who were hospitalized due to COVID-19. RESULTS: Forty-one (1.8%) out of 2315 patients admitted due to severe SARS-CoV-2 pneumonia suffered from an IRD. The admission OR for patients with IRD was 1.91 against the general population, and it was considerably higher in patients with Sjögren syndrome, vasculitis, and systemic lupus erythematosus. Twenty-seven patients were receiving treatment for IRD with corticosteroids, 23 with conventional DMARDs, 12 with biologics (7 rituximab [RTX], 4 anti-tumor necrosis factor [anti-TNF], and 1 abatacept), and 1 with Janus kinase inhibitors. Ten deaths were registered among patients with IRD. A higher hospitalization rate and a higher number of deaths were observed in patients treated with RTX (OR 12.9) but not in patients treated with anti-TNF (OR 0.9). CONCLUSION: Patients with IRD, especially autoimmune diseases and patients treated with RTX, may be at higher risk of severe pneumonia due to SARS-CoV-2 compared to the general population. More studies are needed to analyze this association further in order to help manage these patients during the pandemic.

LAUDES Study: impact of digital ulcers on hand functional limitation, work productivity and daily activities, in systemic sclerosis patients.

The objective of this study was to evaluate the impact of digital ulcers (DUs) in daily life of systemic sclerosis (SSc) Spanish patients. We developed a multicenter observational study to compare functional disability in SSc patients with active DUs vs. those without DUs. An additional correlation between perception of patients and physicians on disability due to DUs was performed. A total of 199 patients were enrolled, 70 (35%) with DUs. Patients with DUs were younger (48 vs. 58 years; p < 0.001) and had more frequently the diffuse subtype of SSc (45 vs. 24%; p = 0.004) than patients without DUs. Patients with DUs showed significantly higher scores in the Cochin Hand Function Scale overall (p < 0.002) and for each of its five dimensions. They also showed higher scores in the Systemic Sclerosis Health Assessment Questionnaire items related to hand function such as, dress and self-care (p < 0.013), eat (p < 0.013) and grip (p < 0.03), and higher Visual Analogic Scale scores for pain (p < 0.013), trouble related with Raynaud's Phenomenon (p < 0.001) and sense of severity (p < 0.004). Impact on daily activities was significantly higher in patients with DUs (p = 0.002), with a non-significant trend to experience higher impact on work productivity (p = 0.07). A high correlation was found between DUs patients and physicians opinion on the impact of DUs (daily life: Pearson R = 0.86; work productivity: Pearson R = 0.87). Study findings show an impaired hand function and increased disability for daily life activities and work productivity in SSc patients with DUs compared with patients without DUs in Spanish population.

A multicenter phase II study of irinotecan (CPT-11) alternated with 5-fluorouracil and leucovorin as first-line treatment of patients with metastatic colorectal cancer.

PURPOSE: In this multicenter phase II study the efficacy and safety of the alternating schedule of irinotecan (CPT-11) with bolus 5-fluorouracil (5-FU) and leucovorin (LV) were assessed as first-line chemotherapy in patients with metastatic colorectal cancer (CRC). PATIENTS AND METHODS: Enrolled in the study were 43 patients with advanced CRC. They received CPT-11 350 mg/m2 i.v. on day 1, alternating with LV 20 mg/m2 i.v. and 5-FU 425 mg/m2 i.v. daily for five consecutive days, on days 22-26 (Mayo Clinic regimen). One cycle consisted of 6 weeks. RESULTS: A total of 179 cycles were administered with a median of four per patient (range one to nine). Efficacy was analyzed on an intention-to-treat basis. The overall objective response rate was 30% (95% CI 16-44), with four complete responses and nine partial responses, whereas 20 patients (4%) showed stable disease. The median time to disease progression was 9.0 months and median survival was 18.5 months. Grade 3/4 diarrhea was mainly related to CPT-11 rather than to 5-FU (9.3% vs 4.7% of patients), whereas grade 3/4 neutropenia was higher during 5-FU administration (16.3% vs 7.0% of patients). CONCLUSIONS: The alternating schedule of CPT-11 with 5 days bolus of 5-FU and low-dose LV showed a clinical benefit in terms of tumor growth control as first-line treatment of patients with metastatic CRC. The overall safety data confirmed this alternating combination as a well-tolerated treatment.

Los graves problemas del Perú ante el congreso

En la presente publicación, aparecen reunidos los proyectos que conceptúo de urgente necesidad y de mayor trascendencia nacionales. Su primera página consigna mi proyecto de ley creando el Consejo Nacional de Control Alimenticio, y siguiendo la trayectoria de cuatro años consagrados al estudio de las causas que más directamente afectan al potencial humano, termina con una autorización constitucional destinada a intensificar la campaña antituberculosa(AU)

Los graves problemas del Perú ante el congreso

En la presente publicación, aparecen reunidos los proyectos que conceptúo de urgente necesidad y de mayor trascendencia nacionales. Su primera página consigna mi proyecto de ley creando el Consejo Nacional de Control Alimenticio, y siguiendo la trayectoria de cuatro años consagrados al estudio de las causas que más directamente afectan al potencial humano, termina con una autorización constitucional destinada a intensificar la campaña antituberculosa