13 research outputs found
Safety of procuring research tissue during a clinically indicated kidney biopsy from patients with lupus: data from the Accelerating Medicines Partnership RA/SLE Network
Objectives In lupus nephritis the pathological diagnosis from tissue retrieved during kidney biopsy drives treatment and management. Despite recent approval of new drugs, complete remission rates remain well under aspirational levels, necessitating identification of new therapeutic targets by greater dissection of the pathways to tissue inflammation and injury. This study assessed the safety of kidney biopsies in patients with SLE enrolled in the Accelerating Medicines Partnership, a consortium formed to molecularly deconstruct nephritis.Methods 475 patients with SLE across 15 clinical sites in the USA consented to obtain tissue for research purposes during a clinically indicated kidney biopsy. Adverse events (AEs) were documented for 30 days following the procedure and were determined to be related or unrelated by all site investigators. Serious AEs were defined according to the National Institutes of Health reporting guidelines.Results 34 patients (7.2%) experienced a procedure-related AE: 30 with haematoma, 2 with jets, 1 with pain and 1 with an arteriovenous fistula. Eighteen (3.8%) experienced a serious AE requiring hospitalisation; four patients (0.8%) required a blood transfusion related to the kidney biopsy. At one site where the number of cores retrieved during the biopsy was recorded, the mean was 3.4 for those who experienced a related AE (n=9) and 3.07 for those who did not experience any AE (n=140). All related AEs resolved.Conclusions Procurement of research tissue should be considered feasible, accompanied by a complication risk likely no greater than that incurred for standard clinical purposes. In the quest for targeted treatments personalised based on molecular findings, enhanced diagnostics beyond histology will likely be required
Transverse-momentum correlations on from mean- fluctuations in Au-Au collisions at 200 GeV
We present first measurements of the pseudorapidity and azimuth
bin-size dependence of event-wise mean transverse momentum
fluctuations for Au-Au collisions at GeV. We invert that
dependence to obtain autocorrelations on differences
interpreted to represent velocity/temperature
distributions on (). The general form of the autocorrelations
suggests that the basic correlation mechanism is parton fragmentation. The
autocorrelations vary strongly with collision centrality, which suggests that
fragmentation is strongly modified by a dissipative medium in the more central
Au-Au collisions relative to peripheral or p-p collisions. \\Comment: 7 pages, 3 figure
A novel non-invasive method of measuring microcirculatory perfusion and blood velocity in infants:a pilot study
Current haemodynamic monitoring is mainly aimed at the macrocirculation. Multiple studies have demonstrated the importance of the microcirculation in relation to the patient’s condition and impact of treatment strategies. However, continuous monitoring of the microcirculation is not yet possible in the neonatal field. A novel dynamic light scattering (DLS) sensor technology for continuous monitoring of the microcirculation was investigated in the neonatal population. Thirty-one haemodynamically stable infants were included. Sequential measurements at the forehead, upper extremity, thorax, abdomen and lower extremity were conducted with the DLS sensor. For analyses stable measurements were selected. The DLS parameters, total blood flow (TBF) and relative blood velocity (RBV), were compared between measurement locations. Changes in relative haemodynamic indices (relHIs), indicating the distribution of blood flow in the microcirculatory blood vessels, were associated with heart rate decelerations. Measurements performed at the forehead had significantly lower TBF levels, compared to measurements at other locations. Early changes in relHIs around a heart rate deceleration were recorded a median (IQR) of 22.0 (13.5–27.0) s before the onset. Measurement of the currently unavailable parameters TBF, RBV and relHIs is possible with DLS technology. Validation of the DLS technology is needed for clinical implementation
Increased Paracetamol Bioavailability after Sleeve Gastrectomy: A Crossover Pre- vs. Post-Operative Clinical Trial
Oral drug bioavailability may be significantly altered after laparoscopic sleeve gastrectomy (LSG), the most popular bariatric procedure worldwide. Paracetamol (acetaminophen) is the post-bariatric analgesic/antipyretic drug of choice. In this work we studied and analyzed the LSG effects on systemic bioavailability and pharmacokinetics of paracetamol after oral administration of solid vs. liquid dosage form. A 4-armed, pharmacokinetic, crossover trial was performed in patients enrolled for LSG. Single paracetamol dose (500 mg), as caplet (n = 7) or syrup (n = 5), was administered before vs. 4–6 months post-LSG. Bioavailability was enhanced after LSG; in the caplet groups, average AUC0–t increased from 9.1 to 18.6 µg·h/mL with AUC0–t difference of 9.5 µg·h/mL (95% CI 4.6–14.5, p = 0.003). Cmax increased from 1.8 (95% CI 1.2–2.5) to 4.2 µg/mL (3.6–4.8) after LSG (p = 0.032). In the syrup groups, AUC0–t increased from 13.4 to 25.6 µg·h/mL, with AUC0–t difference of 12.2 µg·h/mL (95% CI 0.9–23.5, p = 0.049). Cmax changed from 5.4 (95% CI 2.5–8.4) to 7.8 µg/mL (6.1–9.6), and systemic bioavailability was complete (102%) after the surgery. Overall, decreased paracetamol exposure in obesity, with recovery to normal drug levels (caplet) or even higher (syrup) post-LSG, was revealed. In conclusion, attention to paracetamol effectiveness/safety in obesity, and after bariatric surgery, is prudent
Local recurrence outcomes using the 32P intraoperative brachytherapy plaque in the management of malignant lesions of the spine involving the dura
Local tsunami run-up depending on initial localization of the landslide body at submarine slope
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High incidence of proliferative and membranous nephritis in SLE patients with low proteinuria in the Accelerating Medicines Partnership.
ObjectiveDelayed detection of LN associates with worse outcomes. There are conflicting recommendations regarding a threshold level of proteinuria at which biopsy will likely yield actionable management. This study addressed the association of urine protein:creatinine ratios (UPCR) with clinical characteristics and investigated the incidence of proliferative and membranous histology in patients with a UPCR between 0.5 and 1.MethodsA total of 275 SLE patients (113 first biopsy, 162 repeat) were enrolled in the multicentre multi-ethnic/racial Accelerating Medicines Partnership across 15 US sites at the time of a clinically indicated renal biopsy. Patients were followed for 1 year.ResultsAt biopsy, 54 patients had UPCR <1 and 221 had UPCR ≥1. Independent of UPCR or biopsy number, a majority (92%) of patients had class III, IV, V or mixed histology. Moreover, patients with UPCR <1 and class III, IV, V, or mixed had a median activity index of 4.5 and chronicity index of 3, yet 39% of these patients had an inactive sediment. Neither anti-dsDNA nor low complement distinguished class I or II from III, IV, V or mixed in patients with UPCR <1. Of 29 patients with baseline UPCR <1 and class III, IV, V or mixed, 23 (79%) had a UPCR <0.5 at 1 year.ConclusionIn this prospective study, three-quarters of patients with UPCR <1 had histology showing class III, IV, V or mixed with accompanying activity and chronicity despite an inactive sediment or normal serologies. These data support renal biopsy at thresholds lower than a UPCR of 1