Systemic lupus erythematosus (SLE) is the prototypical autoimmune disease that can affect any organ of the body. Multiple mechanisms may contribute to the pathophysiology of systemic lupus, including failure to remove apoptotic bodies, hyperactivity of self-reactive B and T lymphocytes, abnormal exposure to autoantigens, and increased levels of B-cell stimulatory cytokines. The involvement of the kidney, called lupus nephritis (LN), during the course of the disease affects between 30% and 60% of adult SLE patients, and up to 70% of children. LN is an immune-mediated glomerulonephritis that is a common and serious finding in patients with SLE. Nowadays, renal biopsy is considered the gold standard for classifying LN, besides its degree of activity or chronicity. Nevertheless, renal biopsy lacks the ability to predict which patients will respond to immunosuppressive therapy and is a costly and risky procedure that is not practical in the monitoring of LN because serial repetitions would be necessary. Consequently, many serum and urinary biomarkers have been studied in SLE patients for the complementary study of LN, existing conventional biomarkers like proteinuria, protein/creatinine ratio in spot urine, 24 h urine proteinuria, creatinine clearance, among others and non-conventional biomarkers, like Monocyte chemoattractant protein-1 (MCP-1), have been correlated with the histological findings of the different types of LN. In this article, we review the advances in lupus nephritis urinary biomarkers. Such markers ideally should be capable of predicting early sub-clinical flares and could be used to follow response to therapy. In addition, some of these markers have been found to be involved in the pathogenesis of lupus nephritis.
Background: We aimed to examine whether using a high fraction of inspired oxygen (FIO 2 ) in the context of an individualised intra-and postoperative open-lung ventilation approach could decrease surgical site infection (SSI) in patients scheduled for abdominal surgery. Methods: We performed a multicentre, randomised controlled clinical trial in a network of 21 university hospitals from June 6, 2017 to July 19, 2018. Patients undergoing abdominal surgery were randomly assigned to receive a high (0.80) or conventional (0.3) FIO 2 during the intraoperative period and during the first 3 postoperative hours. All patients were mechanically ventilated with an open-lung strategy, which included recruitment manoeuvres and individualised positive end-expiratory pressure for the best respiratory-system compliance, and individualised continuous postoperative airway pressure for adequate peripheral oxyhaemoglobin saturation. The primary outcome was the prevalence of SSI within the first 7 postoperative days. The secondary outcomes were composites of systemic complications, length of intensive care and hospital stay, and 6-month mortality. Results: We enrolled 740 subjects: 371 in the high FIO 2 group and 369 in the low FIO 2 group. Data from 717 subjects were available for final analysis. The rate of SSI during the first postoperative week did not differ between high (8.9%) and low (9.4%) FIO 2 groups (relative risk [RR]: 0.94; 95% confidence interval [CI]: 0.59e1.50; P¼0.90]). Secondary outcomes, such as atelectasis (7.7% vs 9.8%; RR: 0.77; 95% CI: 0.48e1.25; P¼0.38) and myocardial ischaemia (0.6% [n¼2] vs 0% [n¼0]; P¼0.47) did not differ between groups. Conclusions: An oxygenation strategy using high FIO 2 compared with conventional FIO 2 did not reduce postoperative SSIs in abdominal surgery. No differences in secondary outcomes or adverse events were found. Clinical trial registration: NCT02776046.
Cathelicidin LL-37 is an antimicrobial peptide that is synthesized by epithelial cells, neutrophils, or lymphocytes and act as an essential defense mechanism against bacterial, viral, or fungi infection of eukaryotic organisms. However, in recent years, this cathelicidin has gained the interest of the scientific community because, besides its antimicrobial properties, LL-37 is an immunomodulator that can contribute to the development of autoimmune diseases. The other non-antimicrobial function of this cathelicidin is its ability to form complexes with the DNA, stimulating plasmacytoid dendritic cells (pDCs) to produce type I IFN, deciding the course of autoimmune diseases, including systemic lupus erythematosus (SLE). The chronic activation of pDCs by surrounding complexes is a crucial factor for the early development of autoimmunity in SLE patients. This stimulation is given by the complexes (LL-37-DNA/anti-DNA) recognized by the receptor FcγRII on pDCs, allowing its endocytosis and its recognition via TLR9, leading to the activation of pDCs and enhanced type I IFN production. In this article, we reviewed the structure, function, and importance of LL-37 in innate immunity, as well as its biological plausibility in the pathophysiology of autoimmune diseases such as SLE. In this narrative review, we included primary journal articles describing the function, structure, prevalence, and importance of LL-37 in various manifestations of SLE, as well as LL-37 and anti-LL37 antibodies in patients with SLE or other autoimmune diseases. In conclusion, LL-37 is an essential molecule in the pathophysiology of SLE, mainly by its role in increasing the production of IFN by pDCs, which postulates it as a crucial molecule in the pathophysiology of SLE and, given plausibility biology, could serve as a biomarker of the disease.
Background Intravenous immunoglobulin (IVIG) is prepared using purified human plasma. IVIG therapy has immunomodulatory effects on autoimmune diseases, including severe systemic lupus erythematosus (SLE). However, reports of its effects on large cohorts are scarce. Methods This single-center retrospective study included SLE patients treated with at least one IVIG cycle for SLE complications. Demographic data, indications, cycle numbers, and clinical improvement with IVIG were evaluated. SLE Disease Activity Index 2000 (SLEDAI-2K) scores were calculated at admission and after IVIG treatment in order to measure clinical improvement. Results Sixty-three SLE patients treated with IVIG (median age: 29 years; interquartile range 21–36 years; 84.13% female) were included, who received 2 g/kg IVIG for two to five days. Main indications were immune thrombocytopenia, hypogammaglobulinemia, infection during a SLE flare, bicytopenia, and immune hemolytic anemia. Seven patients received more than one IVIG cycle without severe adverse effects. Significant differences were found in SLEDAI-2K scores when the indications were immune thrombocytopenia and hypogammaglobulinemia, with a trend for hemolytic anemia. Patients with concomitant infection, myopathy, and gastrointestinal involvement showed a considerable reduction in their last SLEDAI-2K scores. Fourteen patients died during hospitalization, mainly due to septic shock and active SLE. Conclusions IVIG showed adequate tolerance and effectiveness in selected severe SLE manifestations, mainly hematological involvement. It was useful for concomitant infection.
Introduction. Therapeutic plasma exchange (TPE) is commonly used as treatment of certain autoimmune neurological diseases (ANDs), and its main objective is the removal of pathogenic autoantibodies. Our aim was to describe the clinical profile and the experience with the usage of TPE in patients with ANDs at our institution. Methods. This is an observational retrospective study, including medical records of patients with diagnosis of ANDs who received TPE, between 2011 and 2018. Characteristics of TPE, such as number of cycles, type of replacement solution, and adverse effects, were evaluated. The modified Rankin Scale (mRS) was applied to measure the clinical response after the therapy. Results. 187 patients were included with the following diagnoses: myasthenia gravis (MG), n = 70 (37%); Guillain–Barré syndrome (GBS), n = 53 (28.3%), neuromyelitis optica spectrum disorders (NMOSD), n = 35 (18.7%); chronic inflammatory demyelinating polyneuropathy (CIDP), n = 23 (12.2%); and autoimmune encephalitis (AE), n = 6 (3.2%). The most used types of replacement solution were albumin (n = 131, 70%) and succinylated gelatin (n = 45, 24%). All patients received a median of five cycles (IQR 5-5). Hypotension and hydroelectrolytic disorders were the main complications. After TPE, 99 patients (52.9%) showed improvement in the mRS scores and a statistical significance (p<0.05) was seen between the admission score and after TPE for every diagnosis except for CIDP. Conclusion. TPE has an adequate safety profile, and improvement in functionality in treated patients reflects its effectiveness.
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