A physical hydrogel cross-linked via the host-guest interactions of cucurbit[8]uril and utilised as an implantable drug-delivery vehicle for the brain is described herein. Constructed from hyaluronic acid, this hydrogel is biocompatible and has a high water content of 98%. The mechanical properties have been characterised by rheology and compared with the modulus of human brain tissue demonstrating the production of a soft material that can be moulded into the cavity it is implanted into following surgical resection. Furthermore, effective delivery of therapeutic compounds and antibodies to primary human glioblastoma cell lines is showcased by a variety of in vitro and ex vivo viability and immunocytochemistry based assays.
Introduction We aimed to determine the mortality rate, cause of death, and rate of end-stage kidney disease (ESKD) in adults with nephrotic syndrome (NS). Methods We conducted a national registry–based study, including all 522 adults who had a kidney biopsy for NS in Scotland in 2014–2017. We linked the Scottish Renal Registry to death certificate data. We performed survival and Cox proportional hazards analyses, accounting for competing risks of death and ESKD. We compared mortality rates with those in the age- and sex-matched general population. Results A total of 372 patients had primary NS; 150 had secondary NS. Over a median follow-up of 866 days, 110 patients (21%) died. In patients with primary NS, observed versus population 3-year mortality was 2.1% (95% CI 0.0%–4.6%) versus 0.9% (0.8%–1.0%) in patients aged <60 years and 24.9% (18.4%–30.8%) versus 9.4% (8.3%–10.5%) in those aged ≥60 years. In secondary NS, this discrepancy was 17.1% (5.6%–27.2%) versus 1.1% (0.9%–1.2%) in <60-year-olds and 49.4% (36.6%–59.7%) versus 8.1% (6.6%–9.6%) in ≥60-year-olds. In primary NS, cardiovascular causes accounted for 28% of deaths, compared with 18% in the general population. Eighty patients (15%) progressed to ESKD. Incidence of ESKD by 3 years was 8.4% (95% CI 4.9%–11.7%) in primary and 35.1% (24.3%–44.5%) in secondary NS. Early remission of proteinuria and the absence of early acute kidney injury (AKI) were associated with lower rates of death and ESKD. Conclusions Adults with NS have high rates of death and ESKD. Cardiovascular causes account for excess mortality in primary NS.
Background: There is little information concerning the invasive coronary angiography (ICA) findings of patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) with elevated troponin levels and suspected myocardial infarction (MI). This study analyzed patient characteristics associated with ICA outcomes.Methods: A total of 8,322 patients with AIS or TIA, treated between March 2010 and May 2020, were retrospectively screened for elevated serum troponin I at hospital admission. Patients in whom ICA was performed, due to suspected type 1 MI based on symptoms, echocardiography, and ECG, were categorized according to ICA results (non-obstructive coronary artery disease (CAD): ≥1 stenosis ≥50% but no stenosis ≥80%; obstructive CAD: any stenosis ≥80% or hemodynamically relevant stenosis assessed by FFR/iwFR).Results: Elevated troponin levels were detected in 2,205 (22.5%) patients, of whom 123 (5.6%) underwent ICA (mean age 71 ± 12 years; 67% male). CAD was present in 98 (80%) patients, of whom 51 (41%) were diagnosed with obstructive CAD. Thus, ICA findings of obstructive CAD accounted for 2.3% of patients with troponin elevation and 0.6% of all stroke patients. The clinical hallmarks of myocardial ischemia, including angina pectoris (31 vs. 15%, p < 0.05) and regional wall motion abnormalities (49 vs. 32%, p = 0.07), and increased cardiovascular risk indicated obstructive CAD. While there was no association between lesion site or stroke severity and ICA findings, causal large-artery atherosclerosis was significantly more common in patients with obstructive coronary disease (p < 0.05).Conclusion: The rate of obstructive CAD in patients with stroke or TIA and elevated troponin levels with suspected concomitant type I MI is low. The cumulation of several cardiovascular risk factors and clinical signs of MI were predictive. AIS patients with large-artery atherosclerosis and elevated troponin may represent an especially vulnerable subgroup of stroke patients with risk for obstructive CAD.
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