Profile of Metalloproteinases and Their Association with Inflammatory Markers in Pleural Effusions.

BACKGROUND: Matrix metalloproteinases (MMPs) are responsible for the breakdown of the extracellular matrix and play an important role in the inflammatory processes of pleural exudates. The imbalance between MMPs and their inhibitors (TIMPs) is present in various pathological processes. OBJECTIVE: To evaluate the profile of MMPs and TIMPs in pleural effusions of different etiologies correlated with inflammatory markers. METHODS: The patients with pleural effusion due to tuberculosis (TB), cancer (CA) or transudate were prospectively evaluated. Pleural fluid was submitted to cytological, biochemical, cytokines, MMP, and TIMP analysis. Statistical analysis was performed using ANOVA and Spearman's correlation, and p < 0.05 was considered significant. RESULTS: One hundred and fourteen patients were enrolled, 80 exudates (41 TB and 39 CA) and 34 transudates. The levels of MMP-8 and MMP-9 were higher in exudates compared to transudates. The level of MMP-8 was significantly higher in TB than in CA. TIMP-1 levels were higher in exudates. IL-6, VEGF, and TGF-ß1 showed differences between exudates and transudates. However, IL-6 level was higher in TB than in CA. We found a significant correlation between MMPs and TIMPs with inflammation markers. MMP-1 was correlated with LDH levels. MMP-8 was correlated with LDH, total cell count, neutrophils, and ADA as well as MMP-1 levels. MMP-9 was correlated with IL-6, TGF-ß1, and VEGF. TIMP-1 was correlated with MMP-9 and IL-6. CONCLUSIONS: MMPs and TIMPs are expressed in pleural fluid of different etiologies and correlate with inflammatory mediators. MMPs may be useful in determining the cause of fluid, but more studies are needed to determine the spectrum of diseases associated with the various isoforms of MMPS and TIMPs.

Twelve Months and Counting: Following Clinical Outcomes in Critical COVID-19 Survivors.

Rationale: Recent reports suggest that patients with severe coronavirus disease (COVID-19) often experience long-term consequences of the infection. However, studies on intensive care unit (ICU) survivors are underrepresented. Objectives: We aimed to explore 12-month clinical outcomes after critical COVID-19, describing the longitudinal progress of disabilities, frailty status, frequency of cognitive impairment, and clinical events (rehospitalization, institutionalization, and falls). Methods: We performed a prospective cohort study of survivors of COVID-19 ICU admissions in Sao Paulo, Brazil. We assessed patients every 3 months for 1 year after hospital discharge and obtained information on 15 activities of daily living (basic, instrumental, and mobility activities), frailty, cognition, and clinical events. Results: We included 428 patients (mean age of 64 yr, 61% required invasive mechanical ventilation during ICU stay). The number of disabilities peaked at 3 months compared with the pre-COVID-19 period (mean difference, 2.46; 99% confidence interval, 1.94-2.99) and then decreased at 12 months (mean difference, 0.67; 99% confidence interval, 0.28-1.07). At 12-month follow-up, 12% of patients were frail, but half of them presented frailty only after COVID-19. The prevalence of cognitive symptoms was 17% at 3 months and progressively decreased to 12.1% (P = 0.012 for trend) at the end of 1 year. Clinical events occurred in all assessments. Conclusions: Although a higher burden of disabilities and cognitive symptoms occurred 3 months after hospital discharge of critical COVID-19 survivors, a significant improvement occurred during the 1-year follow-up. However, one-third of the patients remained in worse conditions than their pre-COVID-19 status.