Tunneled Hemodialysis Catheter Tip Design and Risk of Catheter Dysfunction: An Australian Nationwide Cohort Study.

RATIONALE & OBJECTIVE: Hemodialysis catheter dysfunction is an important problem for patients with kidney failure. The optimal design of the tunneled catheter tip is unknown. This study evaluated the association of catheter tip design with the duration of catheter function. STUDY DESIGN: Observational cohort study using data from the nationwide REDUCCTION trial. SETTING & PARTICIPANTS: 4,722 adults who each received hemodialysis via 1 or more tunneled central venous catheters in 37 Australian nephrology services from December 2016 to March 2020. EXPOSURE: Design of tunneled hemodialysis catheter tip, classified as symmetrical, step, or split. OUTCOME: Time to catheter dysfunction requiring removal due to inadequate dialysis blood flow assessed by the treating clinician. ANALYTICAL APPROACH: Mixed, 3-level accelerated failure time model, assuming a log-normal survival distribution. Secular trends, the intervention, and baseline differences in service, patient, and catheter factors were included in the adjusted model. In a sensitivity analysis, survival times and proportional hazards were compared among participants' first tunneled catheters. RESULTS: Among the study group, 355 of 3,871 (9.2%), 262 of 1,888 (13.9%), and 38 of 455 (8.4%) tunneled catheters with symmetrical, step, and split tip designs, respectively, required removal due to dysfunction. Step tip catheters required removal for dysfunction at a rate 53% faster than symmetrical tip catheters (adjusted time ratio, 0.47 [95% CI, 0.33-0.67) and 76% faster than split tip catheters (adjusted time ratio, 0.24 [95% CI, 0.11-0.51) in the adjusted accelerated failure time models. Only symmetrical tip catheters had performance superior to step tip catheters in unadjusted and sensitivity analyses. Split tip catheters were infrequently used and had risks of dysfunction similar to symmetrical tip catheters. The cumulative incidence of other complications requiring catheter removal, routine removal, and death before removal were similar across the 3 tip designs. LIMITATIONS: Tip design was not randomized. CONCLUSIONS: Symmetrical and split tip catheters had a lower risk of catheter dysfunction requiring removal than step tip catheters. FUNDING: Grants from government (Queensland Health, Safer Care Victoria, Medical Research Future Fund, National Health and Medical Research Council, Australia), academic (Monash University), and not-for-profit (ANZDATA Registry, Kidney Health Australia) sources. TRIAL REGISTRATION: Registered at ANZCTR with study number ACTRN12616000830493. PLAIN-LANGUAGE SUMMARY: Central venous catheters are widely used to facilitate vascular access for life-sustaining hemodialysis treatments but often fail due to blood clots or other mechanical problems that impede blood flow. A range of adaptations to the design of tunneled hemodialysis catheters have been developed, but it is unclear which designs have the greatest longevity. We analyzed data from an Australian nationwide cohort of patients who received hemodialysis via a tunneled catheter and found that catheters with a step tip design failed more quickly than those with a symmetrical tip. Split tip catheters performed well but were infrequently used and require further study. Use of symmetrical rather than step tip hemodialysis catheters may reduce mechanical failures and unnecessary procedures for patients.

Effect of a Multifaceted Intervention on the Incidence of Hemodialysis Catheter Dysfunction in a National Stepped-Wedge Cluster Randomized Trial.

Introduction: Effective strategies to prevent hemodialysis (HD) catheter dysfunction are lacking and there is wide variation in practice. Methods: In this post hoc analysis of the REDUcing the burden of dialysis Catheter ComplicaTIOns: a national (REDUCCTION) stepped-wedge cluster randomized trial, encompassing 37 Australian nephrology services, 6361 participants, and 9872 catheters, we investigated whether the trial intervention, which promoted a suite of evidence-based practices for HD catheter insertion and management, reduced the incidence of catheter dysfunction, which is defined by catheter removal due to inadequate dialysis blood flow. We also analyzed outcomes among tunneled cuffed catheters and sources of event variability. Results: A total of 873 HD catheters were removed because of dysfunction over 1.12 million catheter days. The raw incidence was 0.91 events per 1000 catheter days during the baseline phase and 0.68 events per 1000 catheter days during the intervention phase. The service-wide incidence of catheter dysfunction was 33% lower during the intervention after adjustment for calendar time (incidence rate ratio = 0.67; 95% confidence interval [CI], 0.50-0.89; P = 0.006). Results were consistent among tunneled cuffed catheters (adjusted incidence rate ratio = 0.68; 95% CI, 0.49-0.94), which accounted for 75% of catheters (n = 7403), 97.4% of catheter exposure time and 88.2% of events (n = 770). Among tunneled catheters that survived for 6 months (21.5% of tunneled catheters), between 2% and 5% of the unexplained variation in the number of catheter dysfunction events was attributable to service-level differences, and 18% to 36% was attributable to patient-level differences. Conclusion: Multifaceted interventions that promote evidence-based catheter care may prevent dysfunction, and patient factors are an important source of variation in events.

Multifaceted Quality Improvement Interventions to Prevent Hemodialysis Catheter-Related Bloodstream Infections: A Systematic Review.

RATIONALE & OBJECTIVE: Central venous catheters (CVCs) are widely used for hemodialysis but are prone to burdensome and costly bloodstream infections. We determined whether multifaceted quality improvement interventions in hemodialysis units can prevent hemodialysis catheter-related bloodstream infections (HDCRBSI). STUDY DESIGN: Systematic review. SETTING & STUDY POPULATIONS: PubMed, EMBASE, and CENTRAL were searched from inception to April 23, 2022, to identify randomized trials, time-series analyses, and before-after studies that examined the effect of multifaceted quality improvement interventions on the incidence of HDCRBSI or access-related bloodstream infections (ARBSI) among people receiving hemodialysis outside of the intensive care unit (ICU). DATA EXTRACTION: Two people independently extracted data and assessed the risk of bias and quality of evidence using validated tools. ANALYTICAL APPROACH: Intervention effects, validity, and characteristics of studies with the same design were compared. Differences between study designs were described. RESULTS: We included 21 studies from 8,824 identified by our search. Among 15 studies that measured HDCRBSI, 2 methodologically heterogenous cluster randomized trials reported discordant intervention effects, 2 interrupted time-series analyses reported favorable interventions with discordant patterns of effect, and 11 before-after studies reported favorable interventions with a very high risk of bias. Among 6 studies that only measured ARBSI, 1 time-series analysis and 1 before-after study did not find a favorable intervention effect, and 4 before-after studies reported a favorable effect with a very high risk of bias. The overall quality of evidence was low for HDCRBSI and very low for ARBSI. LIMITATIONS: Nine definitions of HDCRBSI were used. Ten studies included hospital-based and satellite facilities but did not report separate intervention effects for each type of facility. CONCLUSIONS: Multifaceted quality improvement interventions may prevent HDCRBSI outside the ICU. However, evidence supporting them is of low quality, and further carefully conducted studies are warranted. REGISTRATION: Registered at PROSPERO with registration number CRD42021252290. PLAIN-LANGUAGE SUMMARY: People with kidney failure rely on central venous catheters to facilitate life-sustaining hemodialysis treatments. Unfortunately, hemodialysis catheters are a common source of problematic bloodstream infections. Quality improvement programs have effectively prevented catheter-related infections in intensive care units, but it is unclear whether they can be adapted to patients using hemodialysis catheters in the community. In a systematic review that included 21 studies, we found that most quality improvement programs were reported to be successful. However, the findings were mixed among higher-quality studies, and overall the quality of evidence was low. Ongoing quality improvement programs should be complemented by more high-quality research.

Energy Absorption and Ballistic Performance of Epoxy Composite Reinforced with Arapaima Scales.

Arapaima scales possess a hierarchical structure capable of absorbing a considerable amount of energy before fracture. These natural dermal armors present significant potential in the sustainable development of cost-effective composites. This work aimed, for the first time, to analyze the impact resistance and ballistic performance of arapaima scale-reinforced epoxy composites and their potential application in multilayered armor systems (MAS). Composite plates were prepared with 20%, 30%, and 40 vol% of arapaima scales. Composite specimens were subjected to notched Izod impact and residual velocity stand-alone tests and their MAS through backface signature (BFS) tests, with their fracture surfaces studied using SEM. The Izod tests confirmed the effect of scales' volume fraction on the energy absorbed by the composites, showing an increase with volume fraction. Residual velocity tests showed that composites with 30 vol% of scales resulted in the most significant improvement in absorbed energy. All MAS formulations presented BFS depths lower than the trauma limit specified by the NIJ standard. Fractographic analysis showed that the scales' toughening mechanisms improved the composites' energy absorption capacity. The experimental results substantiate the potential use of arapaima scales as a reinforcement agent in polymeric composites, with 30 vol% being the optimal volume fraction for energy-absorbing applications.

Jackfruit: Composition, structure, and progressive collapsibility in the largest fruit on the Earth for impact resistance.

The jackfruit is the largest fruit on the Earth, reaching upwards of 35 kg and falling from heights of 25 m. To survive such high energy impacts, it has evolved a unique layered configuration with a thorny exterior and porous tubular underlayer. During compression, these layers exhibit a progressive collapse mechanism where the tubules are first to deform, followed by the thorny exterior, and finally the mesocarp layer in between. The thorns are composed of lignified bundles which run longitudinally from the base of the thorn to the tip and are embedded in softer parenchymal cells, forming a fiber reinforced composite. The mesocarp contains more lignin than any of the other layers while the core appears to contain more pectin giving rise to variations in compressive and viscoelastic properties between the layers. The surface thorns provide a compelling impact-resistant feature for bioinspiration, with a cellular structure that can withstand large deformation without failing and wavy surface features which densify during compression without fracturing. Even the conical shape of the thorns is valuable, presenting a gradually increasing surface area during axial collapse. A simplified model of this mechanism is put forward to describe the force response of these features. The thorns also distribute damage laterally during impact and deflect cracks along their interstitial valleys. These phenomena were observed in 3D printed, jackfruit-inspired designs which performed markedly better than control prints with the same mass. STATEMENT OF SIGNIFICANCE: Many biological materials have evolved remarkable structures that enhance their mechanical performance and serve as sources of inspiration for engineers. Plants are often overlooked in this regard yet certain botanical components, like nuts and fruit, have shown incredible potential as blueprints for improved impact resistant designs. The jackfruit is the largest fruit on Earth and generates significant falling impact energies. Here, we explore the jackfruit's structure and its mechanical capabilities for the first time. The progressive failure imparted by its multilayered design and the unique collapse mode of the surface thorns are identified as key mechanisms for improving the fruit's impact resistance. 3D printing is used to show that these structure-property benefits can be successfully transferred to engineering materials.

Hierarchical modeling of elastic moduli of equine hoof wall.

This study predicts analytically effective elastic moduli of substructures within an equine hoof wall. The hoof wall is represented as a composite material with a hierarchical structure comprised of a sequence of length scales. A bottom-up approach is employed. Thus, the outputs from a lower spatial scale serve as the inputs for the following scale. The models include the Halpin-Tsai model, composite cylinders model, a sutured interface model, and classical laminate theory. The length scales span macroscale, mesoscale, sub-mesoscale, microscale, sub-microscale, and nanoscale. The macroscale represents the hoof wall, consisting of tubules within a matrix at the mesoscale. At the sub-mesoscale, a single hollow tubule is reinforced by a tubule wall made of lamellae; the surrounding intertubular material also has a lamellar structure. The lamellae contain sutured and layered cells at the microscale. A single cell is made of crystalline macrofibrils arranged in an amorphous matrix at the sub-microscale. A macrofibril contains aligned crystalline rod-like intermediate filaments at the nanoscale. Experimentally obtained parameters are used in the modeling as inputs for geometry and nanoscale properties. The predicted properties of the hoof wall material agree with experimental measurements at the mesoscale and macroscale. We observe that the hierarchical structure of the hoof wall leads to a decrease in the elastic modulus with increasing scale, from the nanoscale to the macroscale. Such behavior is an intrinsic characteristic of hierarchical biological materials. This study can serve as a framework for designing impact-resistant hoof-inspired materials and structures.

Development and Characterization of LLDPE Blends with Different UHMWPE Concentrations Obtained by Hot Pressing.

To modify its characteristics, expand its applicability, and, in some cases, its processability, new blends using ultra-high-molecular-weight polyethylene (UHMWPE) have been developed. In this study, three different formulations of linear low-density polyethylene (LLDPE) and UHMWPE blends were prepared with 15, 30, and 45% (% w/w) UHMWPE in the LLDPE matrix. All mixtures were prepared by hot pressing and were immersed in water for one hour afterwards at a controlled temperature of 90 °C to relieve the internal stresses that developed during the forming process. The thermal characterization showed that the blends showed endothermic peaks with different melting temperatures, which may be the result of co-crystallization without mixing between the polymers during the forming process. The mechanical characteristics presented are typical of a ductile material, but with the increase in the percentage of UHMWPE, there was a decrease in the ductility of the blends, as the elongation at rupture of the blends was higher than that of the pure components. The morphologies observed by SEM indicate that there were two phases in the blends. This is the result of the system's immiscibility due to the mode of preparation of the blends, wherein the two polymers may not have mixed intimately, confirming the results found with the thermal analyses.

Equine hoof wall: Structure, properties, and bioinspired designs.

The horse hoof wall exhibits exceptional impact resistance and fracture control due to its unique hierarchical structure which contains tubular, lamellar, and gradient configurations. In this study, structural characterization of the hoof wall was performed revealing features previously unknown. Prominent among them are tubule bridges, which are imaged and quantified. The hydration-dependent viscoelasticity of the hoof wall is described by a simplified Maxwell-Weichert model with two characteristic relaxation times corresponding to nanoscale and mesoscale features. Creep and relaxation tests reveal that the specific hydration gradient in the hoof keratin likely leads to reduced internal stresses that arise from spatial stiffness variations. To better understand realistic impact modes for the hoof wall in-vivo, drop tower tests were executed on hoof wall samples. Fractography revealed that the hoof wall's reinforced tubular structure dominates at lower impact energies, while the intertubular lamellae are dominant at higher impact energies. Broken fibers were observed on the surface of the tubules after failure, suggesting that the physically intertwined nature of the tubule reinforcement and intertubular matrix improves the toughness of this natural fiber reinforced composite. The augmented understanding of the structure-mechanical property relationship in dynamic loading led to the design of additively manufactured bioinspired structures, which were evaluated in quasistatic and dynamic loadings. The inclusion of gradient structures and lamellae significantly reduced the damage sustained in drop tower tests, while tubules increased the energy absorption of samples tested in compact tension. The samples most similar to the hoof wall displayed remarkably consistent fracture control properties. STATEMENT OF SIGNIFICANCE: The horse hoof wall, capable of withstanding large, repeated, dynamic loads, has been touted as a candidate for impact-resistant bioinspiration. However, our understanding of this biological material and its translation into engineered designs is incomplete. In this work, new features of the horse hoof wall are quantified and the hierarchical failure mechanisms of this remarkable material under near-natural loading conditions are uncovered. A model of the hoof wall's viscoelastic response, based on studies of other keratinous materials, was developed. The role of hydration, strain rate, and impact energy on the material's response were elucidated. Finally, multi-material 3D printed designs based on the hoof's meso/microstructure were fabricated and exhibited advantageous energy absorption and fracture control relative to control samples.

Polymeric Composite Reinforced with PET Fiber Waste for Application in Civil Construction as a Cladding Element.

The construction industry contributes enormously to the high levels of carbon dioxide on the planet. For this reason, the sector has been investing in the development of new products that reduce the environmental impact. This study developed a fibrous polymeric composite using industrial residues of polyethylene terephthalate (PET) fibers for application in civil construction as a cladding element. The thermal and morphological characterization of the fiber was performed using Thermogravimetry (TG) and Scanning Electron Microscopy (SEM). Composites with 1, 3, and 5% PET fibers were obtained. Mechanical, morphological properties, chemical resistance, the effect of ultraviolet radiation and water absorption of the composites were evaluated. The results were compared to parameters established by the Brazilian standard NBR 15.575-3. Fibers had a smooth surface but with small surface defects, diameter between 20 and 30 µm and thermal stability up to 325.44 °C. The addition of 5% PET fibers resulted in an increase of more than 300% in the impact resistance of the composites, but with a reduction in the flexural strength. The mechanical and chemical resistance results met the parameters established by the standard used in the study. The degradation chamber test indicated that PET fibers suffered more from exposure to ultraviolet radiation than the polymeric matrix.

The Effect of Dialkyl Peroxide Crosslinking on the Properties of LLDPE and UHMWPE.

Peroxide has been considered a chemical agent that can be used to tune the properties of polymeric materials. This research evaluated the influence of different concentrations of dialkyl peroxides on the mechanical, thermal, and morphological properties of linear low-density polyethylene (LLDPE) and ultra-high molecular weight polyethylene (UHMWPE). The neat polymer, as well as those with the addition of 1% and 2% by mass of dialkyl peroxides, were subjected to compression molding and immersion in water for 1 h, under controlled temperatures of 90 °C. The values of the gel content found in the samples indicated that the addition of peroxide to the LLDPE and to the UHMWPE promoted the formation of a reticulated network. The structure obtained by the crosslinking led to less reorganization of the chains during the crystallization process, resulting in the formation of imperfect crystals and, consequently, in the reduction in melting temperatures, crystallization and enthalpy. The mechanical properties were altered with the presence of the crosslinker. The polymers presented had predominant characteristics of a ductile material, with the occurrence of crazing with an increased peroxide content.

Engineering with keratin: A functional material and a source of bioinspiration.

Keratin is a highly multifunctional biopolymer serving various roles in nature due to its diverse material properties, wide spectrum of structural designs, and impressive performance. Keratin-based materials are mechanically robust, thermally insulating, lightweight, capable of undergoing reversible adhesion through van der Waals forces, and exhibit structural coloration and hydrophobic surfaces. Thus, they have become templates for bioinspired designs and have even been applied as a functional material for biomedical applications and environmentally sustainable fiber-reinforced composites. This review aims to highlight keratin's remarkable capabilities as a biological component, a source of design inspiration, and an engineering material. We conclude with future directions for the exploration of keratinous materials.

Pregnancy Prolongation After Eculizumab Use in Early-Onset Preeclampsia.

BACKGROUND: Untreated microangiopathic hemolytic anemia in pregnancy is associated with adverse maternal and perinatal outcomes. Accurate diagnosis is challenging owing to nonspecific clinical features and pathologic findings. Timely initiation of appropriate management is essential to optimize maternal and perinatal outcomes. CASE: A 26-year-old primiparous woman presented at 20 weeks of gestation with new-onset microangiopathic hemolytic anemia on a background of poorly controlled type 1 diabetes. She received eculizumab for presumed atypical hemolytic uremic syndrome. At 24 weeks of gestation, she developed superimposed early-onset preeclampsia; she delivered at 27 weeks of gestation after continuing eculizumab. CONCLUSION: Eculizumab may prolong pregnancy in early-onset preeclampsia. Additional research is needed to assess short-term and long-term maternal and newborn outcomes.

Association of Metformin Use With Risk of Lactic Acidosis Across the Range of Kidney Function: A Community-Based Cohort Study.

Importance: Approximately 1 million patients in the United States with type 2 diabetes mellitus and mild-to-moderate kidney disease do not receive guideline-directed therapy with metformin. This may reflect uncertainty regarding the risk of acidosis in patients with chronic kidney disease. Objective: To quantify the association between metformin use and hospitalization with acidosis across the range of estimated glomerular filtration rate (eGFR), accounting for change in eGFR stage over time. Design, Setting, and Participants: Community-based cohort of 75 413 patients with diabetes in Geisinger Health System, with time-dependent assessment of eGFR stage from January 2004 until January 2017. Results were replicated in 67 578 new metformin users and 14 439 new sulfonylurea users from 2010 to 2015, sourced from 350 private US health systems. Exposures: Metformin use. Main Outcomes and Measures: Hospitalization with acidosis (International Classification of Diseases, Ninth Revision, Clinical Modification code of 276.2). Results: In the primary cohort (n = 75 413), mean (SD) patient age was 60.4 (15.5) years, and 51% (n = 38 480) of the participants were female. There were 2335 hospitalizations with acidosis over a median follow-up of 5.7 years (interquartile range, 2.5-9.9 years). Compared with alternative diabetes management, time-dependent metformin use was not associated with incident acidosis overall (adjusted hazard ratio [HR], 0.98; 95% CI, 0.89-1.08) or in patients with eGFR 45 to 59 mL/min/1.73 m2 (adjusted HR, 1.16; 95% CI, 0.95-1.41) and eGFR 30 to 44 mL/min/1.73 m2 (adjusted HR, 1.09; 95% CI, 0.83-1.44). On the other hand, metformin use was associated with an increased risk of acidosis at eGFR less than 30 mL/min/1.73 m2 (adjusted HR, 2.07; 95% CI, 1.33-3.22). Results were consistent when new metformin users were compared with new sulfonylurea users (adjusted HR for eGFR 30-44 mL/min/1.73 m2, 0.77; 95% CI, 0.29-2.05), in a propensity-matched cohort (adjusted HR for eGFR 30-44 mL/min/1.73 m2, 0.71; 95% CI, 0.45-1.12), when baseline insulin users were excluded (adjusted HR for eGFR 30-44 mL/min/1.73 m2, 1.16; 95% CI, 0.87-1.57), and in the replication cohort (adjusted HR for eGFR 30-44 mL/min/1.73 m2, 0.86; 95% CI, 0.37-2.01). Conclusions and Relevance: In 2 real-world clinical settings, metformin use was associated with acidosis only at eGFR less than 30 mL/min/1.73 m2. Our results support cautious use of metformin in patients with type 2 diabetes and eGFR of at least 30 mL/min/1.73 m2.