Plasma Wnt7b protein in rheumatoid arthritis: Detection of interstitial lung disease.

OBJECTIVE: To determine the plasma level of Wingless-related integration site 7b (Wnt7b) protein in rheumatoid arthritis (RA) patients (with and without interstitial lung disease (ILD)) and in idiopathic pulmonary fibrosis (IPF) patients and its relationship with RA disease activity and/or severity of pulmonary fibrosis. To assess the validity of plasma Wnt7b for the detection of ILD among RA patients. METHOD: This case-control study included 128 subjects (32 RA-ILD, 32 RA, 32 IPF, and 32 healthy controls). RA and RA-ILD Patients were evaluated for disease activity by DAS28 and disease activity grades were recorded according to DAS28 grades. Laboratory parameters as Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Rheumatoid Factor (RF), Anti-citrullinated peptide (Anti-CCP) were recorded. Plasma Wnt7b levels were measured by ELISA. Diagnosis of pulmonary fibrosis (for RA-ILD and IPF patients) was done by high resolution computed tomography (HRCT) and its severity was assessed mainly by pulmonary function test using forced vital capacity (FVC) grading. RESULTS: Comparison of Wnt7b plasma levels showed a significant difference between the studied groups with the P-value < 0.018 (RA-ILD had the highest levels). Post hoc analysis revealed a significant difference in Wnt7b plasma levels between RA-ILD and IPF groups (P = 0.008). Also, RA-ILD and control groups had a significant difference (P = 0.039). However, there was a non-significant relationship between Wnt7b plasma levels and RA disease activity as well as the severity of pulmonary fibrosis. ROC curve analysis for the plasma Wnt7b levels revealed that a level  ≥285.1 pg/ml had a sensitivity of 87.5% and a specificity of 43.8% for the detection of ILD in RA patients with positive likelihood ratio of 1.56 and negative likelihood ratio of 0.29. CONCLUSION: RA-ILD patients had significantly higher plasma Wnt7b levels than the controls and IPF patients. These data suggest that the Wnt7b secretion is augmented by the concomitant presence of RA with pulmonary fibrosis. In addition, plasma Wnt7b may be used as a highly sensitive test for the detection of immunologically induced fibrotic changes in lung tissue among RA patients.

Carbapenem-Resistant Klebsiella pneumoniae Among Patients with Ventilator-Associated Pneumonia: Evaluation of Antibiotic Combinations and Susceptibility to New Antibiotics.

Background: Carbapenemase-producing Gram-negative bacteria, particularly Klebsiella pneumoniae (K. pneumoniae), are at the forefront of the list of causative agents of ventilator-associated pneumonia (VAP). The treatment options for such infections are limited, and various antimicrobial combinations have been suggested as alternatives in clinical practice. New antibiotics, such as ceftazidime/avibactam, ceftolozane/tazobactam and cefiderocol, have shown advantages in both in vitro and clinical studies. Purpose: To evaluate the in vitro effect of meropenem-ciprofloxacin and meropenem-colistin combinations on carbapenem-resistant (CR) K. pneumoniae VAP isolates and to determine their susceptibility to new antibiotics. Methods: Seventy-three K. pneumoniae isolates from 176 endotracheal samples from VAP cases were studied. Antibiotic susceptibility testing and phenotypic detection of extended-spectrum ß lactamase (ESBL) and carbapenemase production were done. CR K. pneumoniae isolates were tested for the five predominant carbapenemase genes (bla KPC, bla OXA-48, bla NDM, bla VIM, and bla IMP). In vitro evaluation of meropenem-ciprofloxacin and meropenem-colistin combinations was done by MIC test strips. Susceptibility to new antibiotics was tested by disk diffusion method. Results: Sixty-three (86.3%) of the isolates were ESBL producers and 52 (71.2%) were carbapenem resistant. Bla NDM was the most prevalent carbapenemase gene (50%), followed by bla OXA-48, (36.5%) then bla KPC in (11.5%). Bla VIM and bla IMP were not detected. Meropenem-ciprofloxacin combination showed indifferent effect on all isolates, while meropenem-colistin combination showed 25% synergism, 15.4% addition and 59.6% indifference. All (100%) CR K. pneumoniae isolates were resistant to ceftolozane/tazobactam and 79% were resistant to ceftazidime/avibactam, while 96% were sensitive to cefiderocol. Conclusion: A high rate of carbapenem resistance exists among VAP K. pneumoniae isolates. Meropenem-colistin combination and cefiderocol appear to be potential treatment options for infections caused by CR K. pneumoniae. Resistance to the tested new ß-lactam/ß-lactamase inhibitors was high, signifying a major threat.