Management of Extensive Talar Osteolysis with Agility™ Total Ankle Replacement Systems Using Geometric Metal-reinforced Polymethylmethacrylate Cement Augmentation

The Agility™ Total Ankle Replacement System, almost exclusively without polymethylmethacrylate cement fixation, was the most commonly used implant in the United States from 1998 to 2007. Much attention has been given to the intraoperative complications and incision healing-related problems. However, it is the intermediate- and long-term complications, specifically, aseptic osteolysis, talar component loosening, subsidence, and progressive malalignment, that require careful consideration, because the revision options are limited. We describe a technique for management of extensive talar aseptic osteolysis for revision of Agility™ total ankle replacement systems with use of geometric metal-reinforced polymethylmethacrylate cement augmentation. This technique preserves the subtalar joint, provides immediate component stability and restoration of component alignment and height, and is a cost-effective alternative to other available options and still allows for additional revision should late failure occur.     

Innovation in Chemistry,Manufacturing, and Controls—A Regulatory Perspective From Industry

This review describes the landscape of novel modalities such as cell and gene therapies, viruses, other novel biologics, oligomers, and emerging technologies, including modern analytics. We summarize the regulatory history and recent landmark developments in some major markets and examine specific chemistry, manufacturing, and controls (CMC) challenges, including suggestions for exploration of potential science-based approaches in support of regulatory strategy development from an industry perspective. In addition, we evaluate the economic factors contributing to patient access to innovation and discuss the impact of regulation. There is a desperate need for a consistent form of regulation where global approaches to regulatory strategies can be harmonized, and specific CMC challenges can be dealt with using the appropriate science and risk-based tools. Although these tools are well described in current guidance documents, the specifics of applicability to complex novel modalities can still result in differing regulatory advice and outcomes. The future goals for efficiently regulating innovative modalities and technologies could be aided by more regulatory harmonization, regulatory education, and industry cooperation through consortia, enabling industry to supply key information to regulators in a transparent yet well-defined manner, and utilizing mutually understood risk-benefit analyses to produce drugs with appropriate safety, efficacy, and quality characteristics.     

Nanomedicine for acute respiratory distress syndrome: The latest application,targeting strategy,and rational design

Acute respiratory distress syndrome (ARDS) is characterized by the severe inflammation and destruction of the lung air–blood barrier, leading to irreversible and substantial respiratory function damage. Patients with coronavirus disease 2019 (COVID-19) have been encountered with a high risk of ARDS, underscoring the urgency for exploiting effective therapy. However, proper medications for ARDS are still lacking due to poor pharmacokinetics, non-specific side effects, inability to surmount pulmonary barrier, and inadequate management of heterogeneity. The increased lung permeability in the pathological environment of ARDS may contribute to nanoparticle-mediated passive targeting delivery. Nanomedicine has demonstrated unique advantages in solving the dilemma of ARDS drug therapy, which can address the shortcomings and limitations of traditional anti-inflammatory or antioxidant drug treatment. Through passive, active, or physicochemical targeting, nanocarriers can interact with lung epithelium/endothelium and inflammatory cells to reverse abnormal changes and restore homeostasis of the pulmonary environment, thereby showing good therapeutic activity and reduced toxicity. This article reviews the latest applications of nanomedicine in pre-clinical ARDS therapy, highlights the strategies for targeted treatment of lung inflammation, presents the innovative drug delivery systems, and provides inspiration for strengthening the therapeutic effect of nanomedicine-based treatment.     

(iii) Bearing surfaces

Alternative bearings surfaces to polyethylene have reduced wear and have led to improved patient outcomes, allowing younger and more active patients to be considered for joint replacements. These bearing surfaces have been developed largely as a response to osteolysis and loosening associated with polyethylene particulate debris. This has led to the evolution of various forms of cross-linked polyethylene and to the greater use of hard-on-hard bearings. The use of metal-on-metal led to resurfacing hip replacements and to the use of large head metal-on-metal hip replacements. Although metal-on-metal bearings have a number of theoretical advantages, the release of metal debris and ions from some designs has been catastrophic. In the future new bearing surfaces must be more thoroughly tested pre-clinically and in well-designed clinical series.     

Interaction between the photosensitizer lumichrome and human serum albumin: effect of excipients

Lumichrome (Lc) is a photodegradation product of riboflavin that can be used as a photosensitizer (PS) in antibacterial photodynamic therapy (aPDT). The binding of Lc with plasma proteins such as human serum albumin (HSA) could affect its efficiency as PS. Excipients are necessary to prepare stable formulations to be used in aPDT and they may affect the PS-HSA binding. Hydroxypropyl (HP)-α, β, γ-cyclodextrin (CD), polyethylene glycol 400 (PEG400) and Pluronic^® F-127 (PF127) were selected as model excipients in this study. The intrinsic HSA fluorescence quenching and absorption and fluorescence spectroscopy were used to evaluate the Lc-HSA interaction in the absence and presence of excipients. Nano-differential scanning calorimetry (DSC) was used to determine the effect of excipients on HSA. The photostability of the samples was also evaluated. The combined results showed a modest interaction between Lc and HSA which was reduced mainly by HPβCD. No major alterations of the HSA nano-DSC thermogram were observed after addition of excipients. HSA did enhance Lc photodegradation. The presence of PF127 did also induce photochemical destabilization of Lc independent of HSA. In conclusion, HPαCD, HPγCD and PEG400 seemed to be the excipients more suitable for use in topical preparations containing Lc.     

Improvement of Oral Bioavailability and Anti-Tumor Effect of Zingerone Self-Microemulsion Drug Delivery System

This study sought to prepare a self-microemulsion drug delivery system containing zingerone (Z-SMEDDS) to improve the low oral bioavailability of zingerone and anti-tumor effect. Z-SMEDDS was characterized by particle size, zeta potential and encapsulation efficiency, while its pharmacokinetics and anti-tumor effects were also evaluated. Z-SMEDDS had stable physicochemical properties, including average particle size of 17.29 ± 0.07 nm, the zeta potential of -22.81 ± 0.29 mV, and the encapsulation efficiency of 97.96% ± 0.02%. In vitro release studies have shown the release of zingerone released by Z-SMEDDS was significantly higher than free zingerone in different release media. The relative oral bioavailability of Z-SMEDDS was 7.63 times compared with free drug. Meanwhile, the half inhibitory concentration （IC50）of Z-SMEDDS and free zingerone was 8.45 μg/mL and 13.30 μg/mL, respectively on HepG2. This study may provide a preliminary basis for further clinical research and application of Z-SMEDDS.     

大黄贴敷联合复方聚乙二醇电解质散口服对便秘患者肠道准备给药时机的影响

目的探讨大黄贴敷神阙穴和天枢穴联合口服复方聚乙二醇电解质散(PGEP)在便秘患者肠道准备中的给药时机。方法选择行结肠镜检查的便秘患者300例,分3组,各100例。A组检查前1天晚上9点,行中药贴敷神阙穴和天枢穴,检查当天早上5~7点服完PGEP 139.12 g(2 000 ml);B组检查前1天晚上9点行中药贴敷神阙穴和天枢,检查当天上午10~12点服完相同剂量的PGEP;C组检查当天早上5点行中药贴敷神阙穴和天枢穴,早上5~7点服完相同剂量的PGEP。服药后4 h行结肠镜检查。应用Boston肠道准备量表(BBPS)评分,并对肠腔内气泡进行评分,比较3组患者肠道准备有效性、耐受性及安全性。结果 A组的肠镜检查时间(7.25±0.60)min明显短于B组(9.10±0.80)min和C组(10.50±0.55)min;A组的BBPS评分(8.50±0.35)分明显高于B组(7.35±1.25)分和C组(6.65±1.30)分;A组的肠腔内气泡评分(0.25±0.15)分明显低于B组(0.75±0.65)分和C组(0.55±0.50)分;A组肠道准备接受率、再次肠道准备接受率(96.00%、93.00%)明显高于B组(85.00%、70.00%)和C组(90.00%、88.00%);A组的总体不良反应评分(1.45±0.04)分明显低于B组(1.75±0.55)分和C组(1.60±0.25)分。差异均有统计学意义(P0.05)。结论检查前1天晚上9点大黄穴位贴敷联合检查当天早上5~7点口服PGEP对便秘患者行结肠镜检查肠道准备效果好。