Fluid resuscitation, along with the early administration of antibiotics, is the cornerstone of treatment for patients with sepsis. However, whether differences in resuscitation fluids impact on the ...requirements for renal replacement therapy (RRT) remains unclear. To examine this issue, we performed a network meta-analysis (NMA), including direct and indirect comparisons, that addressed the effect of different resuscitation fluids on the use of RRT in patients with sepsis. The data sources MEDLINE, EMBASE, ACPJC, CINAHL and Cochrane Central Register were searched up to March 2014. Eligible studies included randomized trials reported in any language that enrolled adult patients with sepsis or septic shock and addressed the use of RRT associated with alternative resuscitation fluids. The risk of bias for individual studies and the overall certainty of the evidence were assessed. Ten studies (6664 patients) that included a total of nine direct comparisons were assessed. NMA at the four-node level showed that an increased risk of receiving RRT was associated with fluid resuscitation with starch versus crystalloid odds ratio (OR) 1.39, 95 % credibility interval (CrI) 1.17–1.66, high certainty. The data suggested no difference between fluid resuscitation with albumin and crystalloid (OR 1.04, 95 % CrI 0.78–1.38, moderate certainty) or starch (OR 0.74, 95 % CrI 0.53–1.04, low certainty). NMA at the six-node level showed a decreased risk of receiving RRT with balanced crystalloid compared to heavy starch (OR 0.50, 95 % CrI 0.34–0.74, moderate certainty) or light starch (OR 0.70, 95 % CrI 0.49–0.99, high certainty). There was no significant difference between balanced crystalloid and saline (OR 0.85, 95 % CrI 0.56–1.30, low certainty) or albumin (OR 0.82, 95 % CrI 0.49–1.37, low certainty). Of note, these trials vary in terms of case mix, fluids evaluated, duration of fluid exposure and risk of bias. Imprecise estimates contributed to low confidence in most estimates of effect. Among the patients with sepsis, fluid resuscitation with crystalloids compared to starch resulted in reduced use of RRT; the same may be true for albumin versus starch.
Myocardial injury after non-cardiac surgery (MINS), a complication with unclear pathogenesis, occurs within the first 30 days after surgery and worsens prognosis. Hypercoagulability induced by ...surgery might contribute to plaque rupture, with subsequent thrombosis and myocardial injury. This study assessed haemostatic markers before surgery and evaluated their association with MINS.
This is a substudy of VISION, a prospective cohort study of perioperative cardiovascular events. Of 475 consecutive vascular surgery patients, 47 (9.9%) developed MINS, defined as postoperative high-sensitivity troponin ≥50 ng litre−1, with ≥20% elevation from the preoperative concentration. The control group consisted of 84 non-MINS patients matched for patient characteristics and co-morbidities. The following preoperative markers of hypercoagulability and fibrinolysis were measured: antithrombin, factor VIII activity, von Willebrand factor concentration and activity, fibrinogen, D-dimer, plasmin–antiplasmin complex, and tissue plasminogen activator. Moreover, C-reactive protein and CD40L concentrations were measured to assess inflammatory activity.
Patients with MINS compared with the non-MINS group had a significantly higher concentration of factor VIII (186 vs 155%, P=0.006), von Willebrand factor activity (223 vs 160%, P<0.001), von Willebrand factor concentration (317 vs 237%, P=0.02), concentrations of fibrinogen (5.6 vs 4.2 g litre−1, P=0.03), D-dimer (1680.0 vs 1090.0 ng ml−1, P=0.04), plasmin–antiplasmin complex (747 vs 512 ng ml−1, P=0.002) and C-reactive protein (10 vs 4.5 mg litre−1, P=0.02) but not antithrombin (95 vs 94%, P=0.89), tissue plasminogen activator (11 vs 9.7 ng ml−1, P=0.06) and CD40L (8790 vs 8580 pg ml−1, P=0.73).
Preoperative elevation of blood markers of hypercoagulability in patients undergoing vascular surgery is associated with a higher risk of MINS.
NCT00512109.
Objective
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare small to medium-size vessel systemic diseases. As their clinical picture, organ involvement, and factors ...influencing outcome may differ between countries and geographical areas, we decided to describe a large cohort of Polish AAV patients coming from several referral centers—members of the Scientific Consortium of the Polish Vasculitis Registry (POLVAS).
Methods
We conducted a systematic multicenter retrospective study of adult patients diagnosed with AAV between Jan 1990 and Dec 2016 to analyze their clinical picture, organ involvement, and factors influencing outcome. Patients were enrolled to the study by nine centers (14 clinical wards) from seven Voivodeships populated by 22.3 mln inhabitants (58.2% of the Polish population).
Results
Participating centers included 625 AAV patients into the registry. Their distribution was as follows: 417 patients (66.7%) with GPA, 106 (17.0%) with MPA, and 102 (16.3%) with EGPA. Male-to-female ratios were almost 1:1 for GPA (210/207) and MPA (54/52), but EGPA was twice more frequent among women (34/68). Clinical manifestations and organ involvement were analyzed by clinical phenotype. Their clinical manifestations seem very similar to other European countries, but interestingly, men with GPA appeared to follow a more severe course than the women. Fifty five patients died. In GPA, two variables were significantly associated with death: permanent renal replacement therapy (PRRT) and respiratory involvement (univariate analysis). In multivariate analysis, PRRT (OR = 5.3; 95% confidence interval (CI) = 2.3–12.2), respiratory involvement (OR = 3.2; 95% CI = 1.06–9.7), and, in addition, age > 65 (OR = 2.6; 95% CI = 1.05–6.6) were independently associated with death. In MPA, also three variables were observed to be independent predictors of death: PRRT (OR = 5.7; 95% CI = 1.3–25.5), skin involvement (OR = 4.4; 95% CI = 1.02–19.6), and age > 65 (OR = 6.3; 95% CI = 1.18–33.7).
Conclusions
In this first multicenter retrospective study of the Polish AAV patients, we have shown that their demographic characteristics, disease manifestations, and predictors of fatal outcome follow the same pattern as those from other European countries, with men possibly suffering from more severe course of the disease.
The aim of the study was to compare the course of the disease and treatment outcomes in ANCA-positive and ANCA-negative eosinophilic granulomatosis with polyangiitis (EGPA) patients from one Polish ...tertiary referral centre.
Retrospective and prospective cohort study carried out on 50 patients treated in our department between 1998 and 2012. EGPA diagnosis was based on the American College of Rheumatology (ACR) criteria. Treatment protocol was based primarily on the predictive Five Factor Score (FFS) scale. Clinical characteristics of the patients, general symptoms, organ involvement, treatment regimen, and follow-up outcomes were evaluated according to ANCA status.
Fifteen ANCA-positive patients and 35 ANCA-negative patients were enrolled. At the time of diagnosis ANCA-positive patients had a higher incidence of renal involvement (53% vs. 7.7%; p<0.001), skin involvement (93.3% vs. 57.1%; p=0.03), and peripheral neuropathy in the form of mononeuritis multiplex (60% vs. 25.7%; p=0.021). ANCA-negative patients had significantly more frequent cardiac manifestations, but only with regard to the entire period of follow-up (68.6% vs. 33.3%; p=0.021). Patients in both groups were under the same treatment regimens, however steroid dose necessary to maintain remission of the disease was significantly higher in the group of ANCA-positive patients (9±2.5 vs. 7.4±1.9 mg/day of methylprednisolone; p=0.023). The presence of ANCA did not affect the frequency of relapses.
Our results confirm the differences in clinical disease presentation based on ANCA status and indicate that ANCA-positive patients should be treated more aggressively.
New therapies for refractory angina are needed.
Assessment of transendocardial delivery of bone marrow CD133
cells in patients with refractory angina.
Randomized, double-blinded, placebo-controlled ...trial enrolled 31 patients with recurrent Canadian Cardiovascular Society II-IV angina, despite optimal medical therapy, ≥1 myocardial segment with inducible ischemia in Tc-99m SPECT who underwent bone marrow biopsy and were allocated to cells (n=16) or placebo (n=15). Primary end point was absolute change in myocardial ischemia by SPECT. Secondary end points were left ventricular function and volumes by magnetic resonance imaging and angina severity. After 4 months, there were no significant differences in extent of inducible ischemia between groups (summed difference score mean ±SD: 2.60 2.6 versus 3.63 3.6,
=0.52; total perfusion deficit: 3.60 3.6 versus 5.01 4.3,
=0.32; absolute changes of summed difference score: -1.38 5.2 versus -0.73 1.9,
=0.65; and total perfusion deficit: -1.33 3.3 versus -2.19 6.6,
=0.65). There was a significant reduction of left ventricular volumes (end-systolic volume: -4.3 11.3 versus 7.4 11.8,
=0.02; end-diastolic volume: -9.1 14.9 versus 7.4 15.8,
=0.02) and no significant change of left ventricular ejection fraction in the cell group. There was no difference in number of patients showing improvement of ≥1 Canadian Cardiovascular Society class after 1 (41.7% versus 58.3%;
=0.68), 4 (50% versus 33.3%;
=0.63), 6 (70% versus 50.0%;
=0.42), and 12 months (55.6% versus 81.8%;
=0.33) and use of nitrates after 12 months.
Transendocardial CD133
cell therapy was safe. Study was underpowered to conclusively validate the efficacy, but it did not show a significant reduction of myocardial ischemia and angina versus placebo.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01660581.
The microRNAs (miRs) are small non-coding RNAs which regulate expression of multiple genes involved in atherogenesis. MicroRNA are also present in circulation. The aims of this study were: 1) ...assessment of expression level of miR-1, miR-208a and miR-423-5p in plasma in patients with STEMI, stable CAD and healthy individuals; 2) evaluation of correlation between plasma miRs and left ventricle ejection fraction, end- systolic and end-diastolic diameters and troponin release in patients with STEMI.
Study group consisted of 26 patients: 1) acute MI group (N.=17); 2) stable CAD group (N.=4); and 3) subjects with no history of CAD (control group, N.=5). Expression of miR-423-5p, miR-208 and miR-1 was measured in plasma before PCI, 6, 12 and 24 hours later. Expression level ofmiRs was measured using TaqMan® MicroRNA Assays. Expression was assessed by Pfaffl method, and miR-39 was used for normalization of the results.
In stable CAD in comparison to control group the expression level of miR-1, miR-208a and miR-423-5p did not show significant differences. Also there was no significant increase of number of miR copies at 6, 12 and 24 hours after PCI. There was a significantly higher number of miR-423-5p copies in patients with acute MI before the pPCI. After 6, 12 and 24 hours post-procedure the expression level was similar to the control group and significantly lower than the baseline level. Conversely, the expression level of miR-1 and miR-208a were not significantly different than in the control group. In patients with acute MI there were no significant correlations between the expression level of miRs and any of the echocardiographic parameters of LV as well as level of troponin I at any time-point of the follow-up.
Early in acute myocardial infarction the expression of miR-423-5p in plasma is significantly increased with subsequent normalization within 6 hours. Potentially it is an early marker of myocardial necrosis.
Aims
Ischaemic heart failure (IHF) patients have a poor prognosis even with current guideline‐derived therapy. Intramyocardial injections of autologous or allogeneic mesenchymal stromal cells might ...improve cardiac function leading to better clinical outcome.
Methods
The SCIENCE (Stem Cell therapy in IschEmic Non‐treatable Cardiac diseasE) consortium has initiated a Horizon 2020 funded multicentre phase II study in six European countries. It is a double‐blind, placebo‐controlled trial testing the safety and efficacy of allogeneic Cardiology Stem Cell Centre Adipose‐derived Stromal Cells (CSCC_ASC) from healthy donors or placebo in 138 symptomatic IHF patients. Main inclusion criteria are New York Heart Association class II–III, left ventricular ejection fraction < 45% and N‐terminal pro‐B‐type natriuretic peptide levels > 300 pg/mL. Patients are randomized in a 2:1 pattern to receive intramyocardial injections of either CSCC_ASC or placebo. CSCC_ASC and placebo treatments are prepared centralized at Rigshospitalet in 5 mL vials as an off‐the‐shelf product. Vials are distributed to all clinical partners and stored in nitrogen vapour tanks ready to be used directly after thawing. A total of 100 × 106 CSCC_ASC or placebo are injected directly into viable myocardium in the infarct border zone using the NOGA XP system (BDS, Cordis, Johnson & Johnson, USA). Primary endpoint is a centralized core‐laboratory assessed change in left ventricular end‐systolic volume at 6‐month follow‐up measured by echocardiography. The trial started in January 2017, 58 patients were included and treated until July 2018.
Conclusion
The SCIENCE trial will provide clinical data on efficacy and safety of intramyocardial cell therapy of allogeneic adipose‐derived stromal cells from healthy donors in patients with IHF.
Introduction
Granulomatosis with polyangiitis (GPA) is a small vessel vasculitis with a complex pathomechanism. Organ damage in GPA is also mediated by extracellular trap formation (NETosis). We ...analyzed the functional status of phosphoproteins modulating NETosis in neutrophils by the mammalian target of rapamycin (mTOR) pathway in GPA along with NETosis biomarkers.
Methods
Phosphoproteins levels measured in isolated neutrophils from 42 patients with GPA (exacerbation n=21; remission n=21) and 21 healthy controls were compared to serum biomarkers of the disease.
Results
Neutrophils in active disease manifested lowered levels of phosphorylated mTOR
(Ser2448),
PTEN
(Ser380)
and ULK1
(Ser555)
, whereas phosphorylated GSK-3α/β
(Ser21/Ser9)
was elevated. Exacerbation of GPA was characterized by elevated neutrophil dsDNA in serum, circulating mitochondrial DNA, and DNA-MPO complexes. A significant negative correlation between mTOR or PTEN phosphoproteins and biomarkers of GPA activity was also present, reflecting the clinical activity score of GPA. Positive correlations between phosphorylated GSK-3 α/β and circulating mtDNA, DNA-MPO complexes, neutrophil-released dsDNA, or circulating proteins were also significant. Increased serum levels of IGFBP-2, TFF-3, CD147, and CHI3L1 accompanied GPA exacerbation, whereas DPP-IV levels were the lowest in active GPA. Using a principal component analysis basigin, PTEN and mTOR had the highest loadings on the discrimination function, allowing classification between active, remission, and control subjects with 98% performance.
Conclusions
We present evidence that inhibited mTOR signaling accompanies NETosis in patients with GPA. The functional status of phosphoproteins suggests simultaneous activation of NETosis and autophagy. These results give rise to the study of autophagy as a mechanism underlying granuloma formation in GPA.
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