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Background: Platelet transfusions are frequently used in the intensive care unit (ICU), but current practices including used product types, volumes, doses and effects are unknown., Study Design and Methods: Sub-study of the inception cohort study 'Thrombocytopenia and Platelet Transfusions in the ICU (PLOT-ICU)', including acutely admitted, adult ICU patients with thrombocytopenia (platelet count <150 × 10 9 /L). The primary outcome was the number of patients receiving platelet transfusion in ICU by product type. Secondary outcomes included platelet transfusion details, platelet increments, bleeding, other transfusions and mortality., Results: Amongst 504 patients with thrombocytopenia from 43 hospitals in 10 countries in Europe and the United States, 20.8% received 565 platelet transfusions; 61.0% received pooled products, 21.9% received apheresis products and 17.1% received both with a median of 2 (interquartile range 1-4) days from admission to first transfusion. The median volume per transfusion was 253 mL (180-308 mL) and pooled products accounted for 59.1% of transfusions, however, this varied across countries. Most centres (73.8%) used fixed dosing (medians ranging from 2.0 to 3.5 × 10 11 platelets/transfusion) whilst some (mainly in France) used weight-based dosing (ranging from 0.5 to 0.7 × 10 11 platelets per 10 kg body weight). The median platelet count increment for a single prophylactic platelet transfusion was 2 (-1 to 8) × 10 9 /L. Outcomes of patients with thrombocytopenia who did and did not receive platelet transfusions varied., Conclusions: Among acutely admitted, adult ICU patients with thrombocytopenia, 20.8% received platelet transfusions in ICU of whom most received pooled products, but considerable variation was observed in product type, volumes and doses across countries. Prophylactic platelet transfusions were associated with limited increases in platelet counts., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Purpose: Thrombocytopenia (platelet count < 150 × 10 9 /L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients., Methods: We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses., Results: We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4-46.1) had thrombocytopenia; 23.4% (20-26) had thrombocytopenia at ICU admission, and 19.8% (17.6-22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19-2.42)., Conclusion: Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic., (© 2023. The Author(s).)

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapy resulting in increased definitive cure rates or extended disease-free survival in various malignant and nonmalignant hematologic diseases. However, because of the high risk of severe complications of this therapy, up to 50% of patients may require being admitted to the intensive care unit (ICU) to manage life-threatening conditions. We aimed to evaluate the in-hospital mortality of allo-HSCT recipients admitted to the ICU and to identify those variables associated with in-hospital mortality. A 10-year (January 2010 to December 2019), single-center, retrospective study was conducted in Vall d´Hebron University Hospital, Barcelona. We included all consecutive allo-HSCT patients who required admission to the ICU. Baseline and disease-related characteristics were registered. Severity scores and the need for organ support were also assessed on days 1, 3, and 5 of ICU admission. In-hospital mortality-associated independent variables were identified using the Cox proportional hazards regression model. Three hundred twenty-three patients underwent allo-HSCT during the study period, of whom 82 (25%) were admitted to the ICU; 53 (65%) male, with a median age of 51 (38-59) years. Most patients received allo-HSCT for the treatment of lymphoma (20 patients [24%]) or acute leukemia (44 patients [54%]). The median Acute Physiology And Chronic Health Evaluation II score was 23 (17-28), and the median Sequential Organ Failure Assessment (SOFA) score on admission was 9 (7-11). Forty-nine (60%) patients died in the ICU, and 11 (13%) died in the hospital after being discharged from the ICU. Disease-related characteristics were not associated with mortality. Yet, SOFA score on day 1 (hazard ratio [HR]: 1.11 [95% confidence interval {CI}: 1.04-1.02]; P = .002), the need for vasopressors on day 3 (HR: 2.35 [95% CI: 1.27-4.36]; P = .007), and a nondecreasing SOFA score on day 5 (HR: 2.13 [95% CI: 1.03-4.39]; P = .04), were independently associated with in-hospital mortality. Mortality in allo-HSCT patients who require ICU admission remains high. In the present study, SOFA score, the need for vasopressors on day 3, and a nondecreasing SOFA score on day 5 predicted in-hospital mortality., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Chimeric antigen receptor (CAR) T-cell therapy provides long-term remissions in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL). Total metabolic tumor volume (TMTV) assessed by 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) has a confirmed prognostic value in the setting of chemoimmunotherapy, but its predictive role with CAR T-cell therapy is not fully established. Thirty-five patients with R/R LBCL who received CAR T-cells were included in the study. TMTV and maximum standardized uptake value (SUVmax) were measured at baseline and 1-month after CAR T-cell infusion. Best response included 9 (26%) patients in complete metabolic response (CMR) and 16 (46%) in partial metabolic response (PMR). At a median follow-up of 7.6 months, median PFS and OS were 3.4 and 8.2 months, respectively. A high baseline TMTV (≥ 25 cm 3 ) was associated with a lower PFS (median PFS, 2.3 vs. 8.9 months; HR = 3.44 [95% CI 1.18-10.1], p = 0.02). High baseline TMTV also showed a trend towards shorter OS (HR = 6.3 [95% CI 0.83-47.9], p = 0.08). Baseline SUVmax did not have a significant impact on efficacy endpoints. TMTV and SUVmax values showed no association with adverse events. Metabolic tumor burden parameters measured by 18FDG-PET before CAR T-cell infusion can identify LBCL patients who benefit most from this therapy., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Immunotherapy seeks to harness the power of the immune system to eradicate malignant tissues. Despite impressive therapeutic success, however, it can be accompanied by severe adverse effects such as cytokine release syndrome (CRS). These therapies cause the release of a great amount of cytokines, with IL-6 playing a central role, that can potentially lead to multiple organ dysfunction. The diagnosis is based on the presence of compatible clinical symptoms, elevated biomarkers and recent treatment with a biological agent. Mild cases can be managed through symptomatic treatment and fluids, while more severe episodes may need supportive therapy and specific care with the anti-IL-6 receptor monoclonal antibody tocilizumab. Although corticosteroids are also effective, they suppress T-cell activity, and so should only be considered as second line therapy or in cases of severe neurological involvement, since tocilizumab does not cross the blood-brain barrier. Cytokine release syndrome generally has a good prognosis, often being reversible and with a good response to specific treatment. Despite possible concerns about the admission of such patients (mainly with advanced oncological disease), we consider that the Intensive Care Unit should remain an option, since these individuals present a potentially reversible drug-related adverse event and are being treated with a new drug that could change the prognosis of the disorder. Intensive care medicine will become a key component in the management of the complications of modern cancer therapies, dealing with patients presenting an overactive immune system producing organ dysfunction while also trying to maintain treatment efficacy. This is the new paradigm., (Copyright © 2019 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.)

Cryoglobulinemia is characterized by a wide range of causes, symptoms, and outcomes. Hepatitis C virus (HCV) infection is detected in 30%-100% of patients with cryoglobulins. Although more than half the patients with cryoglobulinemic vasculitis present a relatively benign clinical course, some may present with potentially life-threatening situations. We conducted the current study to analyze the clinical characteristics and outcomes of HCV patients presenting with life-threatening cryoglobulinemic vasculitis. We evaluated 181 admissions from 89 HCV patients diagnosed with cryoglobulinemic vasculitis consecutively admitted to our department between 1995 and 2010. In addition, we performed a systematic analysis of cases reported to date through a MEDLINE search.The following organ involvements were considered to be potentially life-threatening in HCV patients with cryoglobulinemic vasculitis: cryoglobulinemic, biopsy-proven glomerulonephritis presenting with renal failure; gastrointestinal vasculitis; pulmonary hemorrhage; central nervous system (CNS) involvement; and myocardial involvement. A total of 279 patients (30 from our department and 249 from the literature search) fulfilled the inclusion criteria: 205 presented with renal failure, 45 with gastrointestinal vasculitis, 38 with CNS involvement, 18 with pulmonary hemorrhage, and 3 with myocardial involvement; 30 patients presented with more than 1 life-threatening cryoglobulinemic manifestation. There were 146 (52%) women and 133 (48%) men, with a mean age at diagnosis of cryoglobulinemia of 54 years (range, 25-87 yr) and a mean age at life-threatening involvement of 55 years (range, 25-87 yr). In 232 (83%) patients, life-threatening involvement was the first clinical manifestation of cryoglobulinemia. Severe involvement appeared a mean of 1.2 years (range, 1-11 yr) after the diagnosis of cryoglobulinemic vasculitis. Patients were followed for a mean of 14 months (range, 3-120 mo) after the diagnosis of life-threatening cryoglobulinemia. Sixty-three patients (22%) died. The main cause of death was sepsis (42%) in patients with glomerulonephritis, and cryoglobulinemic vasculitis itself in patients with gastrointestinal, pulmonary, and CNS involvement (60%, 57%, and 62%, respectively). In conclusion, HCV-related cryoglobulinemia may result in progressive (renal involvement) or acute (pulmonary hemorrhage, gastrointestinal ischemia, CNS involvement) life-threatening organ damage. The mortality rate of these manifestations ranges between 20% and 80%. Unfortunately, this may be the first cryoglobulinemic involvement in almost two-thirds of cases, highlighting the complex management and very elevated mortality of these cases., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To present a pooled analysis of the efficacy of rituximab from European cohorts diagnosed with biopsy-proven lupus nephropathy (LN) who were treated with rituximab., Methods: Consecutive patients with biopsy-proven LN treated with rituximab in European reference centers were included. Complete response (CR) was defined as normal serum creatinine with inactive urinary sediment and 24-hour urinary albumin <0.5 g, and partial response (PR) as a >50% improvement in all renal parameters that were abnormal at baseline, with no deterioration in any parameter., Results: 164 patients were included (145 women and 19 men, with a mean age of 32.3 years). Rituximab was administered in combination with corticosteroids (162 patients, 99%) and immunosuppressive agents in 124 (76%) patients (cyclophosphamide in 58 and mycophenolate in 55). At 6- and 12-months, respectively, response rates were 27% and 30% for CR, 40% and 37% for PR and 33% for no response. Significant improvement in 24-h proteinuria (4.41 g. baseline vs 1.31 g. post-therapy, p=0.006), serum albumin (28.55 g. baseline to 36.46 g. post-therapy, p<0.001) and protein/creatinine ratio (from 421.94 g/mmol baseline to 234.98 post-therapy, p<0.001) at 12 months was observed. A better response (CR+PR) was found in patients with type III LN in comparison with those with type IV and type V (p=0.007 and 0.03, respectively). Nephrotic syndrome and renal failure at the time of rituximab administration predicted a worse response (no achievement of CR at 12 months) (p<0.001 and p=0.024, respectively)., Conclusion: Rituximab is currently being used to treat refractory systemic autoimmune diseases. Rituximab may be an effective option for patients with lupus nephritis, especially those refractory to standard treatment or who experience a new flare after intensive immunosuppressive treatment., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Introduction: The purpose of this observational study was to analyze the rates, characteristics and associated risk factors of severe infections in patients with systemic autoimmune diseases (SAD) who were treated off-label with biological agents in daily practice., Methods: The BIOGEAS registry is an ongoing Spanish prospective cohort study investigating the long-term safety and efficacy of the off-label use of biological agents in adult patients with severe, refractory SAD. Severe infections were defined according to previous studies as those that required intravenous treatment or that led to hospitalization or death. Patients contributed person-years of follow-up for the period in which they were treated with biological agents., Results: A total of 344 patients with SAD treated with biological agents off-label were included in the Registry until July 2010. The first biological therapies included rituximab in 264 (77%) patients, infliximab in 37 (11%), etanercept in 21 (6%), adalimumab in 19 (5%), and 'other' agents in 3 (1%). Forty-five severe infections occurred in 37 patients after a mean follow-up of 26.76 months. These infections resulted in four deaths. The crude rate of severe infections was 90.9 events/1000 person-years (112.5 for rituximab, 76.9 for infliximab, 66.9 for adalimumab and 30.5 for etanercept respectively). In patients treated with more than two courses of rituximab, the crude rate of severe infection was 226.4 events/1000 person-years. A pathogen was identified in 24 (53%) severe infections. The most common sites of severe infection were the lower respiratory tract (39%), bacteremia/sepsis (20%) and the urinary tract (16%). There were no significant differences relating to gender, SAD, agent, other previous therapies, number of previous immunosuppressive agents received or other therapies administered concomitantly. Cox regression analysis showed that age (P = 0.015) was independently associated with an increased risk of severe infection. Survival curves showed a lower survival rate in patients with severe infections (log-rank and Breslow tests < 0.001)., Conclusions: The rates of severe infections in SAD patients with severe, refractory disease treated depended on the biological agent used, with the highest rates being observed for rituximab and the lowest for etanercept. The rate of infection was especially high in patients receiving three or more courses of rituximab. In patients with severe infections, survival was significantly reduced. Older age was the only significant predictive factor of severe infection.

We describe the natural history of lupus nephritis (LN) in a historical cohort of 190 white patients with the diagnosis of biopsy-proven LN followed in a single reference center.We evaluated 670 patients with systemic lupus erythematosus (SLE) consecutively followed in our department from 1970 until 2006. All patients fulfilled the 1997 revised criteria for the classification of SLE. White patients (Spanish-born) with biopsy-proven LN were selected as the study population.The cohort included 190 patients (170 female patients and 20 male) with a mean age at LN diagnosis of 31 years. Renal biopsy revealed type I LN in 8 (4%) patients, type II in 33 (17%), type III in 46 (24%), type IV in 72 (38%), type V in 28 (15%), and type VI in 3 (2%) patients. Induction remission was achieved in 85% of patients with types I and II, 78% with type III, 70% with type IV, and 32% of patients with type V. After a mean follow-up of 2391 patient-years, 62 (33%) patients developed chronic renal failure and 18 (9%) evolved to end-stage renal disease. Adjusted multivariate Cox regression analysis identified male sex (hazard ratio [HR], 4.33) and elevated creatinine at LN diagnosis (HR, 5.18) as independent variables for renal failure. Survival was 92% at 10 years of follow-up, 80% after 20 years, and 72% after 30 years.Our results suggest that biopsy-proven LN in white patients has an excellent prognosis. Ethnicity should be considered a key factor when evaluating the prognosis and therapeutic response to different agents in patients with LN.

Objectives: To analyse the safety and efficacy of the off-label use of rituximab in patients with severe, refractory systemic autoimmune diseases., Methods: In 2006, the Study Group on Autoimmune Diseases of the Spanish Society of Internal Medicine created the BIOGEAS project, a multicenter study devoted to collecting data on the use of biological agents in adult patients with systemic autoimmune diseases refractory to standard therapies (failure of at least two immunosuppressive agents)., Results: One hundred and ninety-six patients with systemic autoimmune diseases treated with rituximab have been included in the Registry (158 women and 38 men, mean age 43 years). Systemic autoimmune diseases included systemic lupus erythematosus (107 cases), inflammatory myopathies (20 cases), ANCA-related vasculitides (19 cases), Sjögren's syndrome (15 cases) and other diseases (35 cases). A therapeutic response was evaluable in 194 cases: 99 (51%) achieved a complete response, 51 (26%) a partial response and 44 (23%) were classified as non-responders. After a mean follow-up of 27.56+/-1.32 months, 44 (29%) out of the 150 responders patients relapsed. There were 40 adverse events reported in 33 (16%) of the 196 patients. The most frequent adverse events were infections, with 24 episodes being described in 19 patients. Thirteen (7%) patients died, mainly due to disease progression (7 cases) and infection (3 cases)., Conclusions: Although not yet licensed for this use, rituximab is currently used to treat severe, refractory systemic autoimmune diseases, with the most favourable results being observed in Sjögren's syndrome, inflammatory myopathies, systemic lupus erythematosus and cryoglobulinemia.

Objective: To analyze published evidence about adalimumab use in autoimmune diseases., Methods: Systematic review of MEDLINE database of citations included from January 1990 to December 2008 employing the terms "adalimumab" and the different systemic autoimmune diseases., Results: Our search identified 241 potentially relevant citations. 154 were retrieved for detailed evaluation. Finally, 18 were selected as relevant, including 54 patients. The reported diseases were as follow: Behçet disease in 16 patients, idiopathic uveitis in 13, sarcoidosis in 5, uveitis associated with rheumatologic diseases in 5 (psoriasis in 2, ankylosing spondylitis in 1, juvenile idiopathic arthritis in 1, Crohn disease in 1), Vogt-Koyanagi-Harada disease in 4, Birdshot uveitis in 4, vasculitis in 3 (1 temporal arteritis, 1 Takayasu's disease, 1 skin vasculitis associated with rheumatoid arthritis), adult onset Still disease in 2, relapsing polychondritis in 1 and systemic sclerosis in 1. The clinical spectrum included uveitis (39 cases), skin and/or mucosae (9), vasculitis (3), arthritis (6), lung (3). These patients were refractory to standard therapy, including corticosteroids (42 cases, 78%), immunosuppressants (42, 78%) and biologics (29, 54%). Fifty (93%) patients responded to adalimumab. The clinical response was similar in those patients who had been treated with other biologic and in those who had not received biologic therapy before adalimumab. The patients were followed for 11.9 months. Twelve (22%) patients relapsed. Five (9%) patients suffer some side effect (3 local skin reaction, 1 angioedema, 1 lung fibrosis). One patient (2%) died due to progression of her disease., Conclusions: Available data about the use of adalimumab in autoinmune diseases come from case reports and uncontrolled studies, that include patients with severe disease and refractory to standard therapy. In this setting, it seems to be an effective and safe treatment option, especially in patients with uveitis and Behçet's disease. This initial data must be confirmed by controlled assays before extending adalimumab use., (Copyright © 2009 Elsevier España, S.L. All rights reserved.)