Tissue Failure Research Articles

Limb Salvage and Pelvic Reconstruction With Endoprosthesis After Pelvic Tumor Resection: A Narrative Review.

Periacetabular defects following tumor resection present formidable challenges in reconstruction and continue to pose clinical difficulties. Historically, treatment approaches leaned towards hindquarter amputation; however, due to associated morbidities and functional limitations, limb-sparing procedures gained prominence in the 1980s. Nevertheless, the intricacies of pelvic anatomy and the imperative of achieving wide surgical margins while preserving essential structures make pelvic tumor resection and subsequent reconstruction inherently complex. Various reconstruction modalities have been explored, including non-vascularized fibular grafts and prosthetic implants. Among these options, the LUMiC® endoprosthesis stands out as a promising solution for pelvic reconstruction post-tumor resection. Characterized by a modular design featuring a hydroxyapatite-coated stem and acetabular cup, this device has shown favorable implant survival rates in studies, despite encountering complications primarily associated with soft tissue failure, dislocation, and infection. Notably, the incidence of complications varies across studies. The Henderson classification system delineates these complications, encompassing soft tissue issues, aseptic loosening, periprosthetic fractures, infections, and tumor recurrence. Despite the encouraging functional outcomes associated with the LUMiC® endoprosthesis, it is not immune to limitations. Concerns persist regarding complications such as dislocation and infection, underscoring the imperative for further research to evaluate the long-term durability and reliability of this reconstructive approach. Moreover, advancements in surgical techniques, perioperative management, and the advent of navigation-assisted procedures hold promise for enhancing outcomes and mitigating complication rates in pelvic reconstruction surgeries.

From the past to the present, optical coherence tomography in glaucoma: a practical guide to a common disease.

Glaucoma comprises a group of disorders of the optic nerve that cause degenerative optic neuropathy, characterised by failure of neuroretinal rim tissue in the optic nerve head, retinal nerve fibre layer, and retinal ganglion cells. Glaucoma imposes a serious epidemiological threat, with an steady increase in the global number of cases. In the current ophthalmological practice, glaucoma is diagnosed via a series of examinations, including routine funduscopic examination, ocular tonometry, gonioscopy, measurement of the visual field, and assessment using the optical coherence tomography (OCT) technique. Nowadays, the OCT technique helps in systematising the diagnostic pathway and is a basic diagnostic tool for detection of early glaucomatous eye changes. It is also vital in assessing progression and monitoring treatment results of patients. The aim of this review was to present the OCT technique as a main tool in diagnosing and monitoring glaucoma.

Detrimental Effects of Chlorhexidine on Articular Cartilage Viability, Matrix, and Mechanics

Background: Chlorhexidine gluconate (CHG) solution is commonly used as an antiseptic irrigation for bacterial decontamination during orthopaedic surgery. Although the chondrotoxicity of CHG on articular cartilage has been reported, the full extent of CHG-related chondrotoxicity and its effects on the extracellular matrix and mechanical properties are unknown. Purpose: To investigate the in vitro effects of a single 1-minute CHG exposure on the viability, biochemical content, and mechanics of native articular cartilage explants. Study Design: Controlled laboratory study. Methods: Articular cartilage explants (6 per group) were harvested from femoral condyles of the porcine stifle and sectioned at tidemark. Explants were bathed in CHG solution (0.05% CHG in sterile water) at varying concentrations (0% control, 0.01% CHG, and 0.05% CHG) for 1 minute, followed by complete phosphate-buffered saline wash and culture in chondrogenic medium. At 7 days after CHG exposure, cell viability, matrix content (collagen and glycosaminoglycan [GAG]), and compressive mechanical properties (creep indentation testing) were assessed. Results: One-minute CHG exposure was chondrotoxic to explants, with both 0.05% CHG (2.6% ± 4.1%) and 0.01% CHG (76.3% ± 8.6%) causing a decrease in chondrocyte viability compared with controls (97.5% ± 0.6%; P < .001 for both). CHG exposure at either concentration had no significant effect on collagen content, while 0.05% CHG exposure led to a significant decrease in mean GAG per wet weight compared with the control group (2.6% ± 1.7% vs 5.2% ± 1.9%; P = .029). There was a corresponding weakening of mechanical properties in explants treated with 0.05% CHG compared with controls, with decreases in mean aggregate modulus (177.8 ± 90.1 kPa vs 280.8 ± 19.8 kPa; P < .029) and shear modulus (102.6 ± 56.5 kPa vs 167.9 ± 16.2 kPa; P < .020). Conclusion: One-minute exposure to CHG for articular cartilage explants led to dose-dependent decreases in chondrocyte viability, GAG content, and compressive mechanical properties. This raises concern for the risk of mechanical failure of the cartilage tissue after CHG exposure. Clinical Relevance: Clinicians should be judicious regarding the use of CHG irrigation at these concentrations in the presence of native articular cartilage.

Epicardial Adipose Tissue and Heart Failure, Friend or Foe?

Heart failure (HF) management guidelines recommend individualized assessments based on HF phenotypes. Adiposity is a known risk factor for HF. Recently, there has been an increased interest in organ-specific adiposity, specifically the role of the epicardial adipose tissue (EAT), in HF risk. EAT is easily assessable through various imaging modalities and is anatomically and functionally connected to the myocardium. In pathological conditions, EAT secretes inflammatory cytokines, releases excessive fatty acids, and increases mechanical load on the myocardium, resulting in myocardial remodeling. EAT plays a pathophysiological role in characterizing both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). In HFrEF, EAT volume is reduced, reflecting an impaired metabolic reservoir, whereas in HFpEF, the amount of EAT is associated with worse biomarker and hemodynamic profiles, indicating increased EAT activity. Studies have examined the possibility of therapeutically targeting EAT, and recent studies using sodium glucose cotransporter 2 inhibitors have shown potential in reducing EAT volume. However, further research is required to determine the clinical implications of reducing EAT activity in patients with HF.

Multilayered Shape-Morphing Scaffolds with a Hierarchical Structure for Uterine Tissue Regeneration.

Owing to dysfunction of the uterus, millions of couples around the world suffer from infertility. Different from conventional treatments, tissue engineering provides a new and promising approach to deal with difficult problems such as human tissue or organ failure. Adopting scaffold-based tissue engineering, three-dimensional (3D) porous scaffolds in combination with stem cells and appropriate biomolecules may be constructed for uterine tissue regeneration. In this study, a hierarchical tissue engineering scaffold, which mimicked the uterine tissue structure and functions, was designed, and the biomimicking scaffolds were then successfully fabricated using solvent casting, layer-by-layer assembly, and 3D bioprinting techniques. For the multilayered, hierarchical structured scaffolds, poly(l-lactide-co-trimethylene carbonate) (PLLA-co-TMC, "PLATMC" in short) and poly(lactic acid-co-glycolic acid) (PLGA) blends were first used to fabricate the shape-morphing layer of the scaffolds, which was to mimic the function of myometrium in uterine tissue. The PLATMC/PLGA polymer blend scaffolds were highly stretchable. Subsequently, after etching of the PLATMC/PLGA surface and employing estradiol (E2), polydopamine (PDA), and hyaluronic acid (HA), PDA@E2/HA multilayer films were formed on PLATMC/PLGA scaffolds to build an intelligent delivery platform to enable controlled and sustained release of E2. The PDA@E2/HA multilayer films also improved the biological performance of the scaffold. Finally, a layer of bone marrow-derived mesenchymal stem cell (BMSC)-laden hydrogel [which was a blend of gelatin methacryloyl (GelMA) and gelatin (Gel)] was 3D printed on the PDA@E2/HA multilayer films of the scaffold, thereby completing the construction of the hierarchical scaffold. BMSCs in the GelMA/Gel hydrogel layer exhibited excellent cell viability and could spread and be released eventually upon biodegradation of the GelMA/Gel hydrogel. It was shown that the hierarchically structured scaffolds could evolve from the initial flat shape into the tubular structure completely in an aqueous environment at 37 °C, fulfilling the requirement for curved scaffolds for uterine tissue engineering. The biomimicking scaffolds with a hierarchical structure and curved shape, high stretchability, and controlled and sustained E2 release appear to be very promising for uterine tissue regeneration.

New Antimicrobial Strategies to Treat Multi-Drug Resistant Infections Caused by Gram-Negatives in Cystic Fibrosis.

People with cystic fibrosis (CF) suffer from recurrent bacterial infections which induce inflammation, lung tissue damage and failure of the respiratory system. Prolonged exposure to combinatorial antibiotic therapies triggers the appearance of multi-drug resistant (MDR) bacteria. The development of alternative antimicrobial strategies may provide a way to mitigate antimicrobial resistance. Here we discuss different alternative approaches to the use of classic antibiotics: anti-virulence and anti-biofilm compounds which exert a low selective pressure; phage therapies that represent an alternative strategy with a high therapeutic potential; new methods helping antibiotics activity such as adjuvants; and antimicrobial peptides and nanoparticle formulations. Their mechanisms and in vitro and in vivo efficacy are described, in order to figure out a complete landscape of new alternative approaches to fight MDR Gram-negative CF pathogens.

Persistence of Urachus in A 7-Month-Old Male Patient with Surgical Resolution: Case Report

Introduction: Patent urachus refers to a rare condition called urachus anomaly. These conditions are caused by the failure of the normal fetal tissue used to empty the fetal bladder to degenerate. Some of these urachal abnormalities are obvious at birth, while others are more subtle and are not diagnosed until adulthood or are discovered only incidentally after imaging for other reasons. Urachal anomalies in children with wet umbilical cord, persistent drainage, recurrent urinary tract infections, and recurrent umbilical cord infections require accurate and timely diagnosis to help relieve symptoms, prevent recurrent serious infections, and ensure timely treatment. Clinical case: The case of a 7-month-old male patient is presented. The mother reports umbilical granuloma of several months of evolution. He goes to a doctor where he suggests an ultrasound examination that rules out persistence of urachus. Mass in umbilical region persists, which is why she comes again. Evolution: By laparoscopic vision, umbilical hernia plus persistence of urachus is evident, findings such as the presence of indirect bilateral inguinal hernia are found. After surgery, the patient recovered satisfactorily. Conclusions: Diagnosis of urachal anomalies can be elusive, but continued drainage of the umbilical cord is a concern in the case of urachal anomalies. Although this condition is usually an isolated finding, the possibility of posterior urethral valves in infants with a patent urachus should not be ruled out.

Two-to-three times increase in natural hip and lumbar non-sagittal plane kinematics can lead to anterior cruciate ligament injury and cartilage failure scenarios during single-leg landings

BackgroundAnalyzing sports injuries is essential to mitigate risk for injury, but inherently challenging using in vivo approaches. Computational modeling is a powerful engineering tool used to access biomechanical information on tissue failure that cannot be obtained otherwise using traditional motion capture techniques. MethodsWe extrapolated high-risk kinematics associated with ACL strain and cartilage load and stress from a previous motion analysis of 14 uninjured participants. Computational simulations were used to induce ACL failure strain and cartilage failure load, stress, and contact pressure in two age- and BMI-matched participants, one of each biological sex, during single-leg cross drop and single-leg drop tasks. The high-risk kinematics were exaggerated in 20% intervals, within their physiological range of motion, to determine if injury occurred in the models. Where injury occurred, we reported the kinematic profiles that led to tissue failure. FindingsOur findings revealed ACL strains up to 9.99%, consistent with reported failure values in existing literature. Cartilage failure was observed in all eight analyzed conditions when increasing each high-risk kinematic parameter by 2.61 ± 0.67 times the participants' natural landing values. The kinematics associated with tissue failure included peak hip internal rotation of 22.48 ± 19.04°, peak hip abduction of 22.51 ± 9.09°, and peak lumbar rotation away from the stance limb of 11.56 ± 9.78°. InterpretationOur results support the ability of previously reported high-risk kinematics in the literature to induce injury and add to the literature by reporting extreme motion limits leading to injurious cases. Therefore, training programs able to modify these motions during single-leg landings may reduce the risk of ACL injury and cartilage trauma.

Transplante de órgãos e tecidos sob o olhar dos profissionais

Abstract The aim of this literature review was to provide theoretical considerations on organ and tissue donation, an effective therapeutic alternative in the treatment of various diseases and in the control of terminal insufficiency of some organs and failure of certain tissues, with the potential to improve the quality of life and living outlook for transplant patients. The main obstacles to carrying out the procedure are the refusal of potential donors’ families, lack of knowledge about the donation-transplant process and scarcity of continuing education policies for health professionals working in the area, and the consequences of lack of knowledge. To change public opinion, this professional must act as an educator, encouraging the population participate in debates on organ transplants and legislation. The number of people on the waiting list is high compared to the total number of donations, despite the positive attitude of the general population towards organ donation.

АНАЛИЗ РЕАЛИЗАЦИИ ПРОГРАММ ЛЕКАРСТВЕННОГО ОБЕСПЕЧЕНИЯ ФЕДЕРАЛЬНЫХ И РЕГИОНАЛЬНЫХ ЛЬГОТОПОЛУЧАТЕЛЕЙ, СТРАДАЮЩИХ САХАРНЫМ ДИАБЕТОМ 2 ТИПА В КАБАРДИНО-БАЛКАРСКОЙ РЕСПУБЛИКЕ

Diabetes mellitus refers to a group of metabolic diseases with chronic hyperglycemia due to impaired insulin secretion or function. At the present stage, many countries are on the threshold of a global "epidemic" of diabetes mellitus. Chronic hyperglycemia leads to damage and failure of various organs and tissues. Therefore, diabetes mellitus, and especially its most common form - type 2 diabetes (DM2), is a serious medical and social problem. An effective approach to therapy of DM2 is highly relevant and depends on many factors and pathogenetic mechanisms. But despite the great progress in this direction, there are still many unresolved issues concerning individualization of treatment, creation of new or selection of already available drugs. This study is devoted to the dynamic analysis of prescription forms prescribed and dispensed to patients suffering from DM2 in the Kabardino-Balkar Republic for 2020-2023. The study found an increase in the total volume of drugs dispensed, the financial volume of expenditures on pharmaceutical care for diabetics with DM2 and costs per patient per year. A significant increase in the number of DM2 patients during the study period is shown. The analysis of prescriptions of oral medicines revealed the continuing trends of predominance of sugar-lowering therapy in medical organizations of the Republic of traditional approaches. Innovative drugs are available only to a small number of patients. It is concluded that the current situation with drug assistance to patients suffering from DM2 requires special attention and control on the part of the republic's health care authorities.

Simulation of fracture in vascular tissue: coupling a continuum damage formulation with an embedded representation of fracture

The fracture of vascular tissue, and load-bearing soft tissue in general, is relevant to various biomechanical and clinical applications, from the study of traumatic injury and disease to the design of medical devices and the optimisation of patient treatment outcomes. The fundamental mechanisms associated with the inception and development of damage, leading to tissue failure, have yet to be wholly understood. We present the novel coupling of a microstructurally motivated continuum damage model that incorporates the time-dependent interfibrillar failure of the collagenous matrix with an embedded phenomenological representation of the fracture surface. Tissue separation is therefore accounted for through the integration of the cohesive crack concept within the partition of unity finite element method. A transversely isotropic cohesive potential per unit undeformed area is introduced that comprises a rate-dependent evolution of damage and accounts for mixed-mode failure. Importantly, a novel crack initialisation procedure is detailed that identifies the occurrence of localised deformation in the continuum material and the orientation of the inserted discontinuity. Proof of principle is demonstrated by the application of the computational framework to two representative numerical simulations, illustrating the robustness and versatility of the formulation.

Tension Parameters of Junctional Tethers in Proximal Junction Kyphosis: A Cadaveric Biomechanical Study

Proximal junctional failure following surgical correction for adult spinal deformity significantly impacts quality of life and increases the economic burden of treating underlying spinal deformity. The objective of this cadaver study was to determine optimal tension parameters in junctional tethers for proximal junctional kyphosis prevention. Cadaveric specimens were used to establish the optimal tension range in polyethylene tethering devices, such as the VersaTie (NuVasive) used in this study. Three specimens were instrumented to test tether tensions of 0, 75, and 150Newtons (N) at L1-L2, T9-T10, and T3-T4. An optical tracking system was used to measure when specimens reached proximal junctional kyphosis, experienced instrumentation or tissue failure, or reached a cap of 2500 cycles. Radiographs were obtained before and after testing. At all levels, use of a tether at tension forces of 75N and 150N elicited a protective effect. The only level in which a higher tension on the tether resulted in more protection was at T3-T4. When averaged, the use of a tether at tension forces of 75N and 150N showed 1000 cycles of protection at L1-L2, 2000 cycles at T9-T10, and 1426 cycles at T3-T4. Radiographic analysis corroborated these findings. The use of a tether in a cadaveric model prevents the development of proximal junctional kyphosis across all tested levels and an increased tension force of 150N is protective at the proximal thoracic spine. These data can be used to develop further models for a tether system that reproducibly applies a fixed tension force above the thoracolumbar rod construct.

Characterizing the Suture Pullout Force for Human Small Bowel.

Performing a small bowel anastomosis, or reconnecting small bowel segments, remains a core competency and critical step for the successful surgical management of numerous bowel and urinary conditions. As surgical education and technology moves toward improving patient outcomes through automation and increasing training opportunities, a detailed characterization of the interventional biomechanical properties of the human bowel is important. This is especially true due to the prevalence of anastomotic leakage as a frequent (3.02%) postoperative complication of small bowel anastomoses. This study aims to characterize the forces required for a suture to tear through human small bowel (suture pullout force, SPOF), while analyzing how these forces are affected by tissue orientation, suture material, suture size, and donor demographics. 803 tests were performed on 35 human small bowel specimens. A uni-axial test frame was used to tension sutures looped through 10 × 20 mm rectangular bowel samples to tissue failure. The mean SPOF of the small bowel was 4.62±1.40 N. We found no significant effect of tissue orientation (p = 0.083), suture material (p = 0.681), suture size (p = 0.131), age (p = 0.158), sex (p = .083), or body mass index (BMI) (p = 0.100) on SPOF. To our knowledge, this is the first study reporting human small bowel SPOF. Little research has been published about procedure-specific data on human small bowel. Filling this gap in research will inform the design of more accurate human bowel synthetic models and provide an accurate baseline for training and clinical applications.

Achilles tendon rupture prevention in physical activity and sports: predisposition factors

Objective: to summarize all clinically significant factors determining the Achilles tendon predisposition to rupture.Materials and methods: the basis of this scientific-analytical review was the analysis of data from the electronic portals PubMed-NCBI, Google Academy, and “Scientific electronic e-Library.ru”.Results: the presented literature review indicates that injuries and ruptures of the Achilles tendon can be provoked by numerous factors, among which genetic predisposition, individual anatomico-morphological features of the tendon complex structure, initial connective tissue failure, pathological changes in the Achilles tendon structure itself, foot and ankle deformities are of great importance. Men are more susceptible to this injury. Tendon injuries are most common either in 30–40 years, or in the period from 60 to 80 years. Professional athletes and people who lead sedentary lifestyles and do not exercise properly are at risk of Achilles tendon ruptures. Concomitant metabolic disorders and use of some medications also play an important role in the predisposition to this injury. Local corticosteroid injections pose a particular tendon rupture risk. The combination of several established factors significantly increases the likelihood of this emergency.Conclusions: early detection of predisposition to Achilles tendon rupture will allow timely development of effective measures for its prevention in physical training and sports.

Translating Cadaveric Injury Risk to Dummy Injury Risk at Iso-energy.

Injury risk assessment based on cadaver data is essential for informing safety standards. The common 'matched-pair' method matches energy-based inputs to translate human response to anthropometric test devices (ATDs). However, this method can result in less conservative human injury risk curves due to intrinsic differences between human and ATDs. Generally, dummies are stiffer than cadavers, so force and displacement cannot be matched simultaneously. Differences in fracture tolerance further influence the dummy risk curve to be less conservative under matched-pair. For example, translating a human lumbar injury risk curve to a dummy of equivalent stiffness using matched-pair resulted in a dummy injury risk over 80% greater than the cadaver at 50% fracture risk. This inevitable increase arises because the dummy continues loading without fracture to attenuate energy beyond the 'matched' cadaver input selected. Human injury response should be translated using an iso-energy approach, as strain energy is well associated with failure in biological tissues. Until cadaver failure, dummy force is related to cadaver force at iso-energy. Beyond cadaver failure, dummy force is related to cadaver force through failure energy. This method does not require perfect cadaver/dummy biofidelity and ensures that energy beyond cadaver failure does not influence the injury risk function.

Aneurysm Rupture Prediction Based on Strain Energy-CFD Modelling.

This paper presents a Patient-Specific Aneurysm Model (PSAM) analyzed using Computational Fluid Dynamics (CFD). The PSAM combines the energy strain function and stress-strain relationship of the dilated vessel wall to predict the rupture of aneurysms. This predictive model is developed by analyzing ultrasound images acquired with a 6-9 MHz Doppler transducer, which provides real-time data on the arterial deformations. The patient-specific cyclic loading on the PSAM is extrapolated from the strain energy function developed using historical stress-strain relationships. Multivariant factors are proposed to locate points of arterial weakening that precede rupture. Biaxial tensile tests are used to calculate the material properties of the artery wall, enabling the observation of the time-dependent material response in wall rupture formation. In this way, correlations between the wall deformation and tissue failure mode can predict the aneurysm's propensity to rupture. This method can be embedded within the ultrasound measures used to diagnose potential AAA ruptures.

Immunosenescence and Inflammaging in COVID-19.

Despite knowledge gaps in understanding the full spectrum of the hyperinflammatory phase caused by SARS-CoV-2, according to the World Health Organization (WHO), COVID-19 is still the leading cause of death worldwide. Susceptible people to severe COVID-19 are those with underlying medical conditions or those with dysregulated and senescence-associated immune responses. As the immune system undergoes aging in the elderly, such drastic changes predispose them to various diseases and affect their responsiveness to infections, as seen in COVID-19. At-risk groups experience poor prognosis in terms of disease recovery. Changes in the quantity and quality of immune cell function have been described in numerous literature sites. Impaired immune cell function along with age-related metabolic changes can lead to features such as hyperinflammatory response, immunosenescence, and inflammaging in COVID-19. Inflammaging is related to the increased activity of the most inflammatory factors and is the main cause of age-related diseases and tissue failure in the elderly. Since hyperinflammation is a common feature of most severe cases of COVID-19, this pathway, which is not fully understood, leads to immunosenescence and inflammaging in some individuals, especially in the elderly and those with comorbidities. In this review, we shed some light on the age-related abnormalities of innate and adaptive immune cells and how hyperinflammatory immune responses contribute to the inflammaging process, leading to clinical deterioration. Further, we provide insights into immunomodulation-based therapeutic approaches, which are potentially important considerations in vaccine design for elderly populations.

Association of Myeloma in Patients of Chronic Kidney Disease; A Single Centered Study

Objective: To evaluate the frequency along with socio-demographic factors and clinical features of myeloma in patients with chronic kidney disease (CKD) presenting at a tertiary care hospital in Karachi, Pakistan. Study design and setting: It was a cross-sectional study conducted at the Department of Nephrology and Hematology, Liaquat National Hospital, Karachi, Pakistan from Jan 2022 to Jul 2022. Methodology: Patients of age&gt;18 years of either gender having chronic kidney disease were included in the study. Detailed data regarding socio-demographic factors, clinical features and presence of multiple myeloma was obtained. Myeloma was diagnosed in the patients using WHO criteria i.e. presence of M-protein in urine or serum, presence of clonal plasma cells in bone marrow, and related tissue or organ failure. Data was entered and analyzed using SPSS version 25. Results: The median age of the patients with chronic kidney disease was 54 years and most of them were males (63%). Myeloma was detected in only 14 patients with CKD. The proportion of myeloma was similar across chronic kidney disease stages, and statistically there was no significant association between chronic kidney disease stages and myeloma with pvalue=0.08. There were no differences in hemoglobin, serum calcium, serum albumin, serum total protein, albumin/globulin (A/G) ratio, ESR, comorbid in patients with and without myeloma (p&gt;0.05). Conclusion: The frequency of myeloma among patients with chronic kidney disease was low.

Amphiphilic (di-)gradient copoly(2-oxazoline)s are potent amyloid fibril formation inhibitors.

Amyloidoses are diseases caused by the accumulation of normally soluble proteins in the form of insoluble amyloids, leading to the gradual dysfunction and failure of various organs and tissues. Inhibiting amyloid formation is therefore an important therapeutic target. We hypothesized that mono- and di-gradient amphiphilic copolymers of hydrophilic 2-(m)ethyl-2-oxazoline and hydrophobic 2-aryl-2-oxazolines may inhibit amyloid fibril formation. In the model system with hen egg white lysozyme (HEWL) as amyloidogenic protein we determined the effect of these polymers on the amyloid formation by making use of the thioflavin T fluorescence, transmission electron microscopy, isothermal titration calorimetry, and dynamic light scattering. We found that some gradient copolymers possess very potent concentration-dependent inhibitory effects on HEWL amyloid formation. Structure-activity relationship revealed that copolymers with higher ratios of aromatic monomeric units had stronger amyloid suppression effects, most plausibly due to the combination of hydrophobic and π-π interactions. The measurements also revealed that the polymers that inhibit amyloid formation most plausibly do so in the form of micelles that interact with the growing amyloid fibril ends, not with isolated HEWL molecules in solution. These findings suggest the potential use of these gradient copolymers as therapeutic agents for amyloidoses.

Hypersensitivity to metals in metal-on-metal hip arthroplasty: a prospective study of one hundred and thirty five lymphocyte transformation tests

BackgroundMetal allergy remains a controversial topic in the orthopaedic community. It is not known if or to what degree metal sensitivity contributes to inflammatory soft tissue failures, unexplained residual pain, or clinical complications after total joint replacement with metal prostheses.MethodsWe investigated the efficacy of the lymphocyte transformation test (LTT) in predicting adverse outcomes in patients after receiving a metal joint replacement. Our study cohort consists of 135 metal-on-metal hip resurfacing arthroplasty cases performed between 2013 and 2015. All study patients had an LTT preoperatively. We retrospectively analyzed clinical outcomes and failures for our cohort.ResultsThere was no difference in LTT reactivity between men and women. Of the 135 patients tested, 46 (34.1% of cohort) tested positive to at least one of the materials comprising their implant, and 78 patients (57.8%) had at least one reactive score to any component of the LTT. After a minimum follow-up of two years, we did not observe an allergic response to the implant in any patients. There were no failures requiring revision. We observed a 2.2% rate of moderate residual pain; no patients with residual pain tested positive for metal sensitivity. When patients with moderate-high LTT reactivity (30.4% of cohort) were compared to the remainder of the study group, there was no difference in HHS or UCLA activity score. There was no correlation between blood metal ion levels and LTT reactivity.ConclusionWe were unable to prove any predictive value of the LTT. We failed to identify hypersensitivity to metals in patients with metal-on-metal hip resurfacing arthroplasty.