Rituximab in the treatment of progressive interstitial lung disease associated with the antisynthetase syndrome.

OBJECTIVE: To assess the real-world, long-term effectiveness of rituximab (RTX) as a rescue therapy in patients with antisynthetase syndrome and progressive interstitial lung disease (ASS-ILD). METHODS: Multicentre observational retrospective longitudinal study of a cohort of patients with ASS-ILD that started treatment with RTX due to recurrent or ongoing progressive ILD despite therapy with glucocorticoids and immunosuppressants. RESULTS: Twenty-eight patients were analyzed. Examining the entire study population, before treatment with RTX the mean decline in %pFVC and %pDLCO from the ASS-ILD diagnosis to the initiation of RTX treatment (T0) was -6.44% and -14.85%, respectively. After six months of treatment, RTX reversed the decline in pulmonary function test (PFT) parameters: ∆%pFVC +6.29% (95% CI: -10.07 to 2.51; p=0.002 compared to T0) and ∆%pDLCO +6.15% (95% CI: -10.86 to -1.43; p=0.013). Twenty-four patients completed one year of therapy and 22 two years, maintaining the response in PFT: ∆%pFVC: +9.93% (95% CI: -15.61 to -4.25; p=0.002) and ∆%pDLCO: +7.66% (95% CI: -11.67 to -3.65; p<0.001). In addition, there was a significant reduction in the median dose of prednisone, and it could be suspended in 18% of cases. In 33% of patients who required oxygen therapy at the start of treatment, it could be discontinued. The frequency of adverse events reached 28.5% of cases. CONCLUSION: Based on our results, RTX appears to be effective as rescue therapy in most patients with recurrent or progressive ASS-ILD unresponsive to conventional treatment. The use of RTX was well tolerated in the majority of patients.

Effectiveness of a thrombin-gelatin flowable for treating severe liver bleeding: an experimental study.

BACKGROUND: Current scientific evidence has pointed out the relevance of hemostatic products for improving clinical outcomes in liver trauma, including increased survival rates and reductions in bleeding-related complications. The purpose of this study was to compare the use of the gelatin-thrombin flowable (Flowable) versus the standard technique of Packing in a new experimental liver injury model. METHODS: Twenty-four swine were prospectively randomized to receive either Flowable or standard packing technique. We used a novel severe liver injury model, in which the middle and left suprahepatic veins were selectively injured, causing an exsanguinating hemorrhage. The main outcome measure was the percentage of lost blood volume. RESULTS: The median total percentage of total blood volume per animal lost, from injury to minute 120, was significantly lower in the Flowable group (15.2%; interquartile range: 10.7-46.7%) than in the Packing group (64.9%; Interquartile range: 53.4-73.0%) (Hodges-Lehmann median difference: 41.1%; 95% CI: 18.9-58.0%, p = 0.0034). The 24-hour survival rate was significantly higher in the Flowable group (87.0%) than in the Packing group (0.0%) (Hazard ratio (HR) 0.08; 95% confidence interval 0.102 to 0.27; p < 0.0001). Mean-arterial pressure was significantly lower at minute 60 and 120 in the Flowable group than in the packing group (p = 0.0258 and p = 0.0272, respectively). At minute 120, hematocrit was higher in the Flowable than in the packing group (Hodges-Lehmann median difference: 5.5%; 95%CI: 1.0 to11.0, p = 0.0267). Finally, the overall-surgical-procedure was significantly shorter with Flowable than with Packing (Hodges-Lehmann median difference: 39.5 s, 95% CI: 25.0 to 54.0 s, p = 0.0004). CONCLUSIONS: The use of the Flowable was more effective in achieving hemostasis, reducing blood loss, and improving survival rates than standard packing in a severe porcine-liver bleeding model.

Multicentre cohort study of acute cholecystitis management during the COVID-19 pandemic.

PURPOSE: To analyse acute cholecystitis (AC) management during the first pandemic outbreak after the recommendations given by the surgical societies estimating: morbidity, length of hospital stay, mortality and hospital-acquired SARS-CoV-2 infection rate. METHODS: Multicentre-combined (retrospective-prospective) cohort study with AC patients in the Community of Madrid between 1st March and 30th May 2020. 257 AC patients were involved in 16 public hospital. Multivariant binomial logistic regression (MBLR) was applied to mortality. RESULTS: Of COVID-19 patients, 30 were diagnosed at admission and 12 patients were diagnosed during de admission or 30 days after discharge. In non-COVID-19 patients, antibiotic therapy was received in 61.3% of grade I AC and 40.6% of grade II AC. 52.4% of grade III AC were treated with percutaneous drainage (PD). Median hospital stay was 5 [3-8] days, which was higher in the non-surgical treatment group with 7.51 days (p < 0.001) and a 3.25% of mortality rate (p < 0.21). 93.3% of patients with SARS-CoV-2 infection at admission were treated with non-surgical treatment (p = 0.03), median hospital stay was 11.0 [7.5-27.5] days (p < 0.001) with a 7.5% of mortality rate (p > 0.05). In patients with hospital-acquired SARS-CoV-2 infection, 91.7% of grade I-II AC were treated with non-surgical treatment (p = 0.037), with a median hospital stay of 16 [4-21] days and a 18.2% mortality rate (p > 0.05). Hospital-acquired infection risk when hospital stay is > 7 days is OR 4.7, CI 95% (1.3-16.6), p = 0.009. COVID-19 mortality rate was 11.9%, AC severity adjusted OR 5.64 (CI 95% 1.417-22.64). In MBLR analysis, age (OR 1.15, CI 95% 1.02-1.31), SARS-CoV-2 infection (OR 14.49, CI 95% 1.33-157.81), conservative treatment failure (OR 8.2, CI 95% 1.34-50.49) and AC severity were associated with an increased odd of mortality. CONCLUSION: In our population, during COVID-19 pandemic, there was an increase of non-surgical treatment which was accompanied by an increase of conservative treatment failure, morbidity and hospital stay length which may have led to an increased risk hospital-acquired SARS-CoV-2 infection. Age, SARS-CoV-2 infection, AC severity and conservative treatment failure were mortality risk factors.

Real-world clinical effectiveness of rituximab rescue therapy in patients with progressive rheumatoid arthritis-related interstitial lung disease.

OBJECTIVE: To assess the real-world, long-term effectiveness of rituximab (RTX) as a rescue therapy in patients with progressive rheumatoid arthritis-related interstitial lung disease (RA-ILD) in whom more conventional therapy has failed. METHODS: Longitudinal retrospective observational study of a cohort of patients with RA-ILD that started treatment with RTX due to ongoing progressive ILD despite treatment with glucocorticoids and csDMARDs or immunosuppressants (IS). All patients were treated with two or more cycles of RTX and evaluated for at least 12 months. Ongoing therapy with csDMARDs or IS remained unchanged. RESULTS: Thirty-one patients were analyzed. Before initiation of RTX the mean decline (delta) in %pFVC and %pDLCO from the ILD diagnosis (median 21 months) was -16.5% and -19.7%, respectively. After 1 year of treatment, RTX was able to reverse the decline of pulmonary function test (PFTs) parameters: ∆%pFVC +8.06% compared to baseline (95% CI: -10.9 to -5.2; p<0.001) and ∆%pDLCO +12.7% (95% CI: -16.3 to -9.1; p<0.001). In addition, there was a significant reduction in the median dose of prednisone, and it could be suspended in 26% of cases. Dividing the population into UIP and non-UIP patterns, we observed a significant increase in PFTs parameters in both groups. In the 25 patients (80.6%) that completed 2 years of treatment, the statistically significant amelioration in PFTs parameters observed at one year was maintained: ∆%pFVC +11.2% (95% CI: -15.6 to -6.8; p<0.001) and ∆%pDLCO +14.8% (95% CI: -19.3 to -10.3; p<0.001). At the end of the follow-up period (median 32 months; IQR 25th-75th 26-64), only 23 of the 31 patients (74.2%) were still undergoing treatment with RTX: in 3 cases (10%) it was stopped due to adverse events, in another 3 (10%) treatment failed ultimately requiring a lung transplant, and 2 patients (6%) died due to progression of the ILD and infectious complications. The frequency of adverse events reached 32% of cases. CONCLUSION: Based on our results, RTX appears to be effective as rescue therapy in a considerable proportion of patients with progressive RA-ILD unresponsive to conventional treatment.

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.

Incidence, associated factors and clinical impact of severe infections in a large, multicentric cohort of patients with systemic lupus erythematosus.

OBJECTIVES: To estimate the incidence of severe infection and investigate the associated factors and clinical impact in a large systemic lupus erythematosus (SLE) retrospective cohort. METHODS: All patients in the Spanish Rheumatology Society Lupus Registry (RELESSER) who meet ≥4 ACR-97 SLE criteria were retrospectively investigated for severe infections. Patients with and without infections were compared in terms of SLE severity, damage, comorbidities, and demographic characteristics. A multivariable Cox regression model was built to calculate hazard ratios (HRs) for the first infection. RESULTS: A total of 3658 SLE patients were included: 90% female, median age 32.9 years (DQ 9.7), and mean follow-up (months) 120.2 (±87.6). A total of 705 (19.3%) patients suffered ≥1 severe infection. Total severe infections recorded in these patients numbered 1227. The incidence rate was 29.2 (95% CI: 27.6-30.9) infections per 1000 patient years. Time from first infection to second infection was significantly shorter than time from diagnosis to first infection (p < 0.000). Although respiratory infections were the most common (35.5%), bloodstream infections were the most frequent cause of mortality by infection (42.0%). In the Cox regression analysis, the following were all associated with infection: age at diagnosis (HR = 1.016, 95% CI: 1.009-1.023), Latin-American (Amerindian-Mestizo) ethnicity (HR = 2.151, 95% CI: 1.539-3.005), corticosteroids (≥10mg/day) (HR = 1.271, 95% CI: 1.034-1.561), immunosuppressors (HR = 1.348, 95% CI: 1.079-1.684), hospitalization by SLE (HR = 2.567, 95% CI: 1.905-3.459), Katz severity index (HR = 1.160, 95% CI: 1.105-1.217), SLICC/ACR damage index (HR = 1.069, 95% CI: 1.031-1.108), and smoking (HR = 1.332, 95% CI: 1.121-1.583). Duration of antimalarial use (months) proved protective (HR = 0.998, 95% CI: 0.997-0.999). CONCLUSIONS: Severe infection constitutes a predictor of poor prognosis in SLE patients, is more common in Latin-Americans and is associated with age, previous infection, and smoking. Antimalarials exerted a protective effect.

Shrinking lung syndrome in systemic lupus erythematosus: A case series and review of the literature.

Shrinking lung syndrome (SLS) is a rare and less known complication mainly associated with systemic lupus erythematosus (SLE). In this study, we analyze the clinical features, investigation findings, approaches to management, and outcome in a case series of 9 adult patients with SLE and SLS diagnosed during a 35-year period in 3 referral tertiary care hospitals in Spain. Additionally, we reviewed 80 additional cases previously reported (PubMed 1965-2015). These 80 cases, together with our 9 patients, form the basis of the present analysis.The overall SLS prevalence in our SLE population was 1.1% (9/829). SLS may complicate SLE at any time over its course, and it usually occurs in patients without previous or concomitant major organ involvement. More than half of the patients had inactive lupus according to SELENA-systemic lupus erythematosus disease activity index (SLEDAI) scores. Typically, it presents with progressive exertional dyspnea of variable severity, accompanied by pleuritic chest pain in 76% of the cases.An important diagnostic delay is common. The diagnostic tools that showed better yield for SLS detection are the imaging techniques (chest x-ray and high-resolution computed tomography) along with pulmonary and diaphragmatic function tests. Evaluation of diaphragm dome motion by M-mode ultrasonography and phrenic nerve conduction studies are less useful.There are no standardized guidelines for the treatment of SLS in SLE. The majority of patients were treated with medium or high doses of glucocorticoids. Several immunosuppressive agents have been used in conjunction with steroids either if the patient fails to improve or since the beginning of the treatment. Theophylline and beta-agonists, alone or in combination with glucocorticoids, have been suggested with the intent to increase diaphragmatic strength.The overall long-term prognosis was good. The great majority of patients had significant clinical improvement and stabilization, or mild to moderate improvement on pulmonary function tests. The mortality rate was very low.

Relationship between damage clustering and mortality in systemic lupus erythematosus in early and late stages of the disease: cluster analyses in a large cohort from the Spanish Society of Rheumatology Lupus Registry.

OBJECTIVES: To identify patterns (clusters) of damage manifestations within a large cohort of SLE patients and evaluate the potential association of these clusters with a higher risk of mortality. METHODS: This is a multicentre, descriptive, cross-sectional study of a cohort of 3656 SLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestations were identified. Then, overall clusters were compared as well as the subgroup of patients within every cluster with disease duration shorter than 5 years. RESULTS: Three damage clusters were identified. Cluster 1 (80.6% of patients) presented a lower amount of individuals with damage (23.2 vs 100% in clusters 2 and 3, P < 0.001). Cluster 2 (11.4% of patients) was characterized by musculoskeletal damage in all patients. Cluster 3 (8.0% of patients) was the only group with cardiovascular damage, and this was present in all patients. The overall mortality rate of patients in clusters 2 and 3 was higher than that in cluster 1 (P < 0.001 for both comparisons) and in patients with disease duration shorter than 5 years as well. CONCLUSION: In a large cohort of SLE patients, cardiovascular and musculoskeletal damage manifestations were the two dominant forms of damage to sort patients into clinically meaningful clusters. Both in early and late stages of the disease, there was a significant association of these clusters with an increased risk of mortality. Physicians should pay special attention to the early prevention of damage in these two systems.