Prognostic role of NK cell percentages in bronchoalveolar lavage from patients with different fibrotic interstitial lung diseases.

BAL cellularity and lymphocyte immunophenotyping offer insights into lung inflammatory status. Natural killer (NK) cells are efficient effector cells, producing pro-inflammatory cytokines. A better understanding of the biology of NK cells in BAL in the lungs is necessary to improve the pathogenesis of fibrotic ILD and develop prospective targeted treatments. Our aim was to analyse NK and NKT-like cell percentages in BAL from 159 patients with different ILD: f-HP, f-NSIP, IPF and CTD-ILD, to evaluate their potential diagnostic/prognostic role. BAL NK cell percentages showed significantly higher values in IPF than in f-HP and f-NSIP, while BAL NKT-like cells showed significantly lower values in the f-NSIP than the f-HP and IPF. A cut-off of 4%NK cells in BAL of IPF showed a significant difference in survival rate. It suggests a possible new marker of survival and raises the possibility of new targeted approach in treatment and management of IPF.

Serial KL-6 measurements in COVID-19 patients.

SARS-CoV2-induced direct cytopathic effects against type II pneumocytes are suspected to play a role in mediating and perpetuating lung damage. The aim of this study was to evaluate serum KL-6 behavior in COVID-19 patients to investigate its potential role in predicting clinical course. Sixty patients (median age IQR, 65 (52-69), 43 males), hospitalized for COVID-19 at Siena COVID Unit University Hospital, were prospectively enrolled. Twenty-six patients were selected (median age IQR, 63 (55-71), 16 males); all of them underwent follow-up evaluations, including clinical, radiological, functional, and serum KL-6 assessments, after 6 (t1) and 9 (t2) months from hospital discharge. At t0, KL-6 concentrations were significantly higher than those at t1 (760 (311-1218) vs. 309 (210-408) p = 0.0208) and t2 (760 (311-1218) vs 324 (279-458), p = 0.0365). At t0, KL-6 concentrations were increased in patients with fibrotic lung alterations than in non-fibrotic group (755 (370-1023) vs. 305 (225-608), p = 0.0225). Area under the receiver operating curve (AUROC) analysis showed that basal KL-6 levels showed good accuracy in discriminating patients with fibrotic sequelae radiologically documented (AUC 85%, p = 0.0404). KL-6 concentrations in patients with fibrotic involvement were significantly reduced at t1 (755 (370-1023) vs. 290 (197-521), p = 0.0366) and t2 (755 (370-1023) vs. 318 (173-435), p = 0.0490). Serum concentrations of KL-6 in hospitalized COVID-19 patients may contribute to identify severe patients requiring mechanical ventilation and to predict those who will develop pulmonary fibrotic sequelae in the follow-up.

Paricalcitol and endothelial function in chronic kidney disease trial.

Altered vitamin D metabolism and low levels of the active form of this vitamin, 1,25-dihydroxy-vitamin D, is a hallmark of chronic kidney disease (CKD), but there is still no randomized controlled trial testing the effect of active forms of vitamin D on vascular function in patients with CKD. Paricalcitol and ENdothelial fuNction in chronic kidneY disease (PENNY) is a double-blinded randomized controlled trial (ClinicalTrials.gov, NCT01680198) testing the effect of an active form of vitamin D, paricalcitol (2 µg/d×12 weeks) on endothelium-dependent and endothelium-independent vasodilatation in 88 patients with stage 3 to 4 CKD and parathormone >65 pg/mL (paricalcitol, n=44; placebo, n=44). Paricalcitol treatment reduced parathormone (-75 pg/mL; 95% confidence interval, -90 to -60), whereas parathormone showed a small rise during placebo (21 pg/mL; 95% confidence interval, 5-36). Blood pressure did not change in both study arms. Baseline flow-mediated dilation was identical in patients on paricalcitol (3.6±2.9%) and placebo (3.6±2.9%) groups. After 12 weeks of treatment, flow-mediated dilation rose in the paricalcitol but not in the placebo group, and the between-group difference in flow-mediated dilation changes (the primary end point, 1.8%; 95% confidence interval, 0.3-3.1%) was significant (P=0.016), and the mean proportional change in flow-mediated dilation was 61% higher in paricalcitol-treated patients than in placebo-treated patients. Such an effect was abolished 2 weeks after stopping the treatment. No effect of paricalcitol on endothelium-independent vasodilatation was registered. Paricalcitol improves endothelium-dependent vasodilatation in patients with stage 3 to 4 CKD. Findings in this study support the hypothesis that vitamin D may exert favorable effects on the cardiovascular system in patients with CKD.

Ultrafiltration intensification in hemodialysis patients improves hypertension but increases AV fistula complications and cardiovascular events.

INTRODUCTION: Hypertension remains a major problem in hemodialysis (HD) patients. METHODS: We performed a pragmatic trial (Pragmatic Clinical Intervention on Blood Pressure Driven by Audit [CLINIDEA]) testing the effectiveness and safety of a 6-month multimodal intervention in hypertensive HD patients regarding the application of higher ultrafiltration (UF) rates or longer or more frequent dialyses in UF-intolerant patients, and an educational intervention to encourage patients to lower their salt and fluid intake. RESULTS: Blood pressure (BP) in hypertensive patients (n=32) fell from 156.8 ± 13.3 / 81.1 ± 8.9 mm Hg to 147.9 ± 18.8 / 77.5 ± 11.1 mm Hg. UF intensification was well tolerated, and the BP goal was achieved without resorting to longer or more frequent dialyses. BP changes were paralleled by a consistent (p<0.01) fall in dry body weight. The trial largely failed at increasing compliance with salt prescription (salt intake: baseline: 156.9 ± 64 mEq/day, 6-month: 150.7 ± 60.3 mEq/day). During the 12 months preceding the trial, the hospitalization rates for arteriovenous (AV) fistula complications and cardiovascular (CV) events were identical in hypertensive and in normotensive patients. However, these complications selectively increased (AV complications: relative risk [RR] = 7.6; CV complication: RR=8.4) in hypertensive patients coinciding with UF intensification during the trial. Increasing the UF rate is an effective BP-lowering intervention in HD patients. However, this intervention is associated with a higher risk for AV complications and CV events. CONCLUSION: Longer and/or more frequent dialyses and better efforts to increase compliance to low salt diets than those put in place in this study are needed to reduce the high prevalence of hypertension in the HD population.