In routine intensive care unit (ICU) practice, fluids are often administered without a safety limit, which may lead to fluid overload and decreased survival. Recently, B-lines score (BLS) has been validated as a lung ultrasound (LUS) quantification of pulmonary congestion. This suggests that LUS may provide a safety threshold to conduct fluid therapy and to avoid overhydration. However, there is no randomized study to test the utility of LUS in guiding fluid management in ICU patients by using a pre-specified BLS cut-off value as a threshold for fluid removal. LUS Guided Fluid Management Protocol for the Critically Ill Patient is a prospective, multi-centre, randomized controlled trial. Five hundred ICU patients will be randomly assigned in a 1:1 ratio, to protocolized LUS-based fluid management or usual care. The trial intervention will start on ICU admission and will consist in daily assessment of BLS and triggered evacuation of excessive fluids with loop diuretics (Furosemide) when BLS ≥ 15. If rebalancing volume status with diuretics fails, forced evacuation by ultrafiltration will be used. The main endpoint is death from all causes at 28 days from randomization. The secondary outcomes are presence and time-course evolution of organ dysfunctions, ICU- and hospital length of stay, all-cause mortality at 90 days, and health economics data. If study results will show that LUS guided fluid management protocol improves outcome in ICU patients, it will be the base for other studies to refine this protocol or track those categories of critically ill patients to whom it may bring maximum benefits. ClinicalTrials.gov, NCT03393065 . Registered on 8 January 2018.

Lupus nephritis (LN) is a common clinical manifestation of systemic lupus erythematosus (SLE). Our study aims to quantitatively analyze CD4+ and CD8+ lymphocytes in different areas and LN classes and describe a specific distribution pattern that is correlated with the severity of LN-specific lesions. In total, 53 LN renal biopsies were immunohistochemically investigated using anti-CD4 and anti-CD8 antibodies. T lymphocytes were counted in 3 areas, including intraglomerular, periglomerular, and interstitial regions. The severity of glomerular and tubulo-interstitial lesions was assessed using an original semi-quantitative algorithm based on the renal corpuscle score (RC_S) and the tubulo-interstitial score (TI_S). The number of CD8+ T lymphocytes was higher than that of CD4+ T lymphocytes in each of the three areas and in each LN class, showing statistically significant differences. ANOVA analysis of all LN classes showed significant differences between periglomerular and interstitial CD4+ and CD8+ T lymphocytes, respectively. Irrespective of location, the number of CD8+ T lymphocytes statistically correlates with the RC_S and the TI_S; no significant correlations were found between the number of CD4+ T lymphocytes and the RC_S and the TI_S for all three considered areas. Our data provide strong evidence supporting the major role of CD8+ lymphocytes in LN lesion progression, with CD4+ lymphocytes playing a limited role.

The value of lung ultrasound (LU) in assessing extravascular lung water (EVLW) was demonstrated by comparing LU with gold-standard methods for EVLW assessment. However, few studies have analysed the value of B-Line score (BLS) in guiding fluid management during critical illness. The purpose of this trial was to evaluate if a BLS-guided fluid management strategy could improve fluid balance and short-term mortality in surgical intensive care unit (ICU) patients. We conducted a randomised, controlled trial within the ICUs of two university hospitals. Critically ill patients were randomised upon ICU admission in a 1:1 ratio to BLS-guided fluid management (active group) or standard care (control group). In the active group, BLS was monitored daily until ICU discharge or day 28 (whichever came first). On the basis of BLS, different targets for daily fluid balance were set with the aim of avoiding or correcting moderate/severe EVLW increase. The primary outcome was 28-day mortality. Over 24 months, 166 ICU patients were enrolled in the trial and included in the final analysis. Trial results showed that daily BLS monitoring did not lead to a different cumulative fluid balance in surgical ICU patients as compared to standard care. Consecutively, no difference in 28-day mortality between groups was found (10.5% vs. 15.6%, p = 0.34). However, at least 400 patients would have been necessary for conclusive results.