Search

Background: Diagnosis of urinary tract infections (UTIs) is a frequent challenge at the emergency department (ED). The clinical usefulness of the urine Gram stain (GS) is uncertain. Objective: We studied the GS performance to clarify its clinical utility at the ED. Methods: Urine dipstick (UD), automated urinalysis (UF-1000i), GS and urine culture (UC) were performed in a cohort of consecutive adults presenting at the ED suspected of a UTI. GS performance was assessed and compared to UD and UF-1000i. Results: A UTI diagnosis was established in 487/1358 (35.9%) episodes. Sensitivity and specificity for 'many' GS leucocytes was 33.7% and 95.4%; for 'many' GS bacteria 51.3% and 91.0%. GS diagnostic performance by ROC analysis was 0.796 for leucocytes and 0.823 for bacteria. GS bacteria performed better than UD nitrite comparable to UF-1000i bacteria. GS leucocytes underperformed compared to UD leucocyte esterase and UF-1000i leucocytes. UC was positive in 455 episodes. GS correctly predicted urine culture of gram-negative rods (PPV 84.6%). Prediction was poor for gram-positive bacteria (PPV 38.4% (cocci), 1.0% (rods)). Conclusion: With the exception of a moderate prediction of gram-negative bacteria in the UC, urine GS does not improve UTI diagnosis at the ED compared to other urine parameters. [ABSTRACT FROM AUTHOR]

Objectives Granulomatosis with polyangiitis (GPA) is a chronic relapsing systemic autoimmune vasculitis. Current treatment of GPA is unsatisfactory, as it relies on strong immunosuppressive regimens, with either CYC or rituximab, which reduce the immunogenicity of several vaccines and are risk factors for a severe form of COVID-19. This emphasizes the need to identify new drug targets and to develop treatment strategies with less harmful side effects. Since CD4+ effector memory T cells (TEM) play a key role in the pathogenesis of GPA, we aimed in this study to modulate CD4+TEM cell activity via Kv1.3 blockade using the specific peptide inhibiter, ShK-186. Methods Peripheral blood samples from 27 patients with GPA in remission and 16 age- and sex-matched healthy controls (HCs) were pre-incubated in vitro in the presence or absence of ShK-186, followed by stimulation with phorbol myristate acetate, calcium ionophore and brefeldin-A. The effect of ShK-186 on the cytokine production (IFNγ, TNFα, IL-4, IL-17, IL-21) within total and subsets of CD4+ T helper (CD4+TH) cells were assessed using flow cytometry. Results ShK-186 reduced the expression level of IFNγ, TNFα, IL-4, IL-17 and IL-21 in CD4+TH cells from patients with GPA in vitro. Further analysis performed on sorted CD4+T cell subsets, revealed that ShK-186 predominantly inhibited the cytokine production of CD4+TEM cells. ShK-186 treatment reduced the production of the pro-inflammatory cytokines to the level seen in CD4+ TH cells from HCs. Conclusions Modulation of cellular effector function by ShK-186 may constitute a novel treatment strategy for GPA with high specificity and less harmful side effects. [ABSTRACT FROM AUTHOR]

Anti-neutrophil cytoplasmic antibody--associated (ANCA-associated) small vessel necrotizing vasculitis is caused by immune-mediated inflammation of the vessel wall and is diagnosed in some cases by the presence of myeloperoxidase-specific antibodies (MPO-ANCA). [...]

A multicenter, randomized, double-blind, double-dummy, noninferiority trial of rituximab was conducted to compare rituximab with standard cytotoxic therapy for the induction of complete remission by 6 months in patients with severe ANCA-associated vasculitis. Rituximab therapy was not found to be inferior to daily cyclophosphamide treatment for induction of remission in severe ANCA-associated vasculitis and might be superior in relapsing disease.

Renal expression of MMP-2, -9, and tissue inhibitor of MMP-1 (TIMP-1) correlates with histological disease activity in anti-neutrophil cytoplasm autoantibody (ANCA)-associated vasculitis (AAV). We studied whether urinary and plasma levels of MMP-2, -9, and TIMP-1 reflect renal expression of these proteins and renal disease-activity in AAV. Urine and plasma samples of patients with AAV who underwent a renal biopsy were collected (n = 32). Urinary activity of MMP-2 and -9 was measured by activity assays. Urinary and plasma levels of MMP-2, MMP-9, and TIMP-1 proteins were measured by ELISA. Healthy controls provided plasma and urine for comparison (n = 31). In patients, the relationship of urinary and plasma levels with renal expression of MMP-2 and MMP-9 and clinical and histological disease activity was studied. Renal MMP expression was compared between patients and controls (n = 8). Urinary MMP-2 and MMP-9 activity and urinary and plasma TIMP-1 levels were significantly higher in patients than in controls. In glomeruli of patients, both MMP-2 and MMP-9 expression reflected active glomerular inflammation. Urinary activity of MMP-2 and MMP-9 did not correlate with renal MMP expression or plasma levels. Urinary MMP activity correlated negatively with glomerular inflammation, but positively with fibrous crescents. Urinary MMP-2 and TIMP-1 levels showed a positive correlation with tubulointersritial damage and a negative correlation with creatinine clearance. Urinary MMP-2, MMP-9, and TIMP-1 are elevated in AAV but do not reflect renal MMP expression and glomerular inflammation. However, urinary MMP-2 activity and TIMP-1 levels reflect tubulointersritial damage and correlate negatively with creatinine clearance at biopsy. ANCA-associated vasculitis; crescentic glomerulonephritis; MMP-2; MMP-9; TIMP-1; immunohistochemistry; urinary levels; plasma levels