Acute Kidney Allograft Rejection Following Coronavirus mRNA Vaccination: A Case Report.

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Multi-Disciplinary Vascular Access Care and Access Outcomes in People Starting Hemodialysis Therapy.

BACKGROUND AND OBJECTIVES: Fistulas, the preferred form of hemodialysis access, are difficult to establish and maintain. We examined the effect of a multidisciplinary vascular access team, including nurses, surgeons, and radiologists, on the probability of using a fistula catheter-free, and rates of access-related procedures in incident patients receiving hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We examined vascular access outcomes in the first year of hemodialysis treatment before (2004-2005, preteam period) and after the implementation of an access team (2006-2008, early-team period; 2009-2011, late-team period) in the Calgary Health Region, Canada. We used logistic regression to study the probability of fistula creation and the probability of catheter-free fistula use, and negative binomial regression to study access-related procedure rates. RESULTS: We included 609 adults (mean age, 65 [±15] years; 61% men; 54% with diabetes). By the end of the first year of hemodialysis, 102 participants received a fistula in the preteam period (70%), 196 (78%) in the early-team period (odds ratios versus preteam, 1.47; 95% confidence interval, 0.92 to 2.35), and 139 (66%) in the late-team period (0.85; 0.54 to 1.35). Access team implementation did not affect the probability of catheter-free use of the fistula (odds ratio, 0.87; 95% confidence interval, 0.52 to 1.43, for the early; and 0.89; 0.52 to 1.53, for the late team versus preteam period). Participants underwent an average of 4-5 total access-related procedures during the first year of hemodialysis, with higher rates in women and in people with comorbidities. Catheter-related procedure rates were similar before and after team implementation; relative to the preteam period, fistula-related procedure rates were 40% (20%-60%) and 30% (10%-50%) higher in the early-team and late-team periods, respectively. CONCLUSION: Introduction of a multidisciplinary access team did not increase the probability of catheter-free fistula use, but resulted in higher rates of fistula-related procedures.

Clinical trials in minimal change disease.

Minimal change disease (MCD) is a pathological condition characterized by subtle glomerular lesions causing massive and reversible proteinuria that is usually steroid sensitive. Recurrence of symptoms of active disease following successful treatment (including proteinuria, oedema and oliguria) and steroid toxicity requires the use of other drugs to attain or maintain remission. Unresolved MCD is considered the initial step in the pathological pathway leading to focal and segmental glomerulosclerosis (FSGS). Historically, cyclophosphamide, chlorambucil, mycophenolate and calcineurin inhibitors have been utilized with success in MCD; however, the chronic nature of the disease and the toxicity of long-term use of these medications has pushed the development of new therapies. Synthetic corticotropin (adrenocorticotropic hormone) and anti-CD20 monoclonal antibodies, for example, are currently under investigation in clinical trials. In addition, these new interventions have dramatically impacted our understanding of the mechanisms of the disease. Phase II-IV clinical trials targeting new mechanisms and/or molecules are in progress. The list is long and includes drugs blocking the adaptive immune system (abatacept and anti-CD40 antibodies), as well as retinoids and the sialic acid precursor N-acetyl-D-mannosamine (ManNAc), two agents that affect the sieving properties of the glomerular basement membrane. Other drugs are being tested against FSGS and, if successful, could also be utilized against MCD. Clinical trials currently in progress should furnish a proper solution to what appears to be a solvable problem.

Atrial fibrillation and chronic kidney disease: struggling through thick and thin.

The prevalence of atrial fibrillation and the risk of stroke display an age-related increase in the chronic kidney disease (CKD) population. Evidence from large randomized controlled trials conducted in the general population supports the use of anticoagulation to reduce the risk of stroke in the setting of non-valvular atrial fibrillation. However, data in the non-dialysis-dependent and dialysis-dependent CKD populations are limited largely to observational studies, which demonstrate conflicting results regarding the risk-benefit profile of anticoagulation. The paradoxical increase in bleeding and thromboembolism that is observed in CKD further complicates decision-making on the use of anticoagulation. Several observational studies suggest an increased risk of bleeding that parallels the decline in renal function, with the highest rates of bleeding seen in the dialysis-dependent population, whereas other studies have not demonstrated any appreciable increase in bleeding risks with anticoagulation. Bleeding rates are largely driven by increased rates of gastrointestinal bleeding with anticoagulation, with minimal contribution of intra-cranial bleeding. Similarly, several studies have suggested lower rates of ischemic stroke and systemic thromboembolism with anticoagulation in people with CKD, whereas other studies have demonstrated no difference in rates of ischemic stroke. Given the paucity of high-quality evidence, and the high prevalence of atrial fibrillation in people with CKD, large randomized control trials are needed to provide recommendations for anticoagulation in this setting.

Real-time imaging of interactions between dipalmitoylphosphatidylcholine monolayers and gelatin based nanoparticles using Brewster angle microscopy.

Given the current interest in the pulmonary route for targeted drug delivery, assessing the impact of drug delivery vehicles on the surfactant layer lining the surface of the lung alveoli is critical. As gelatin-based nanoparticles are one such vehicle, this study addresses their interaction with the major saturated phospholipid component of native lung surfactant, dipalmitoylphosphatidylcholine (DPPC). Nanoparticles are colloidal particles in the size range of 1 to 1000 nm that are presently investigated for site-specific drug delivery in the emerging field of nanomedicine. Monolayer studies of DPPC films were performed both in the presence and absence of nanoparticles in order to assess the interaction in terms of average molecular areas occupied at given surface pressures. In Brewster angle microscopy experiments, nanoparticles significantly changed the shape and reduced the size of DPPC domains suggesting a considerable interaction of the two systems. For safe pulmonary drug delivery, understanding this interaction is a prerequisite so nanoparticles can be a feasible alternative to more conventional therapies in the future.

Size dependent interactions of nanoparticles with lung surfactant model systems and the significant impact on surface potential.

The relationship between a model pulmonary surfactant system and various sized nanoparticles was investigated in this study. Diplamitoylphosphatidylcholine (DPPC) is the main lipid constituent of lung surfactant and has the ability to reach very high surface pressures (around 70 mN/m) upon compression. Due to these properties it was used as a model to simulate the lung surfactant film in vitro. The first objective of this study was to investigate the relationship between DPPC and various sized nanoparticles within the subphase through surface pressure-area isotherms. The second objective was to measure the surface potential of the different preparations (conducted on a mini-Langmuir trough) and to determine if an optimal nanoparticle size exists possessing a greater affinity for the DPPC film compared to other sizes. The results from the pressure area isotherms indicate that the interaction between DPPC and the nanoparticles is stable and that the 235 nm particles may represent an optimal size. Furthermore, the results from the surface potential experiments confirm that an interaction of the nanoparticles with the monolayer exists as indicated by surface-pressure area isotherms. Any even moderate interaction between nanoparticles and lung surfactant film might reduce or increase the surface potential of the surfactant film, and this might impact the deposition of the nanoparticles or other ligands which may be positively or negatively charged drugs within the surfactant film. Thus changes in surface potential due to nanoparticle interactions have to be taken into account for future drug targeting studies using nano-sized drug carriers.

An elevated level of cholesterol impairs self-assembly of pulmonary surfactant into a functional film.

In adult respiratory distress syndrome, the primary function of pulmonary surfactant to strongly reduce the surface tension of the air-alveolar interface is impaired, resulting in diminished lung compliance, a decreased lung volume, and severe hypoxemia. Dysfunction coincides with an increased level of cholesterol in surfactant which on its own or together with other factors causes surfactant failure. In the current study, we investigated by atomic force microscopy and Kelvin-probe force microscopy how the increased level of cholesterol disrupts the assembly of an efficient film. Functional surfactant films underwent a monolayer-bilayer conversion upon contraction and resulted in a film with lipid bilayer stacks, scattered over a lipid monolayer. Large stacks were at positive electrical potential, small stacks at negative potential with respect to the surrounding monolayer areas. Dysfunctional films formed only few stacks. The surface potential of the occasional stacks was also not different from the surrounding monolayer. Based on film topology and potential distribution, we propose a mechanism for formation of stacked bilayer patches whereby the helical surfactant-associated protein SP-C becomes inserted into the bilayers with defined polarity. We discuss the functional role of the stacks as mechanically reinforcing elements and how an elevated level of cholesterol inhibits the formation of the stacks. This offers a simple biophysical explanation for surfactant inhibition in adult respiratory distress syndrome and possible targets for treatment.