Correction: Clodronate-nintedanib-loaded exosome-liposome hybridization enhances the liver fibrosis therapy by inhibiting Kupffer cell activity.

Correction for 'Clodronate-nintedanib-loaded exosome-liposome hybridization enhances the liver fibrosis therapy by inhibiting Kupffer cell activity' by Keqin Ji et al., Biomater. Sci., 2022, 10, 702-713, https://doi.org/10.1039/D1BM01663F.

Comparison of Glenohumeral Bone Morphology Between Patients With Versus Without Anterior Shoulder Instability.

Background: The stability of the glenohumeral joint is associated with anatomic characteristics including bony structures and soft tissues. Purpose: To compare the differences in specific bony glenohumeral geometries between shoulders with anterior shoulder instability (ASI), unaffected contralateral shoulders, and healthy control shoulders. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Shoulder computed tomography (CT) scans of 36 patients with ASI and 36 matched healthy controls were retrieved and 3-dimensionally reconstructed. We measured the glenoid radius of curvature (GROC) in the anterior-posterior (AP) and superior-inferior directions, humeral head radius of curvature (HROC) in the AP direction, conformity index, glenoid height, glenoid width, glenoid index, stability angle, glenoid version, and glenoid depth. The differences between the groups were statistically calculated. CT scans of the unaffected contralateral shoulders from 21 of the ASI patients were also collected to identify the consistency of the bony structures in bilateral shoulders. Results: Patients with ASI had greater GROC in the AP direction (P < .001), HROC in the AP direction (P = .002), glenoid height (P = .005), and glenoid index (P < .001) and smaller conformity index (P < .001), glenoid width (P = .002), stability angle (P < .001), and glenoid depth (P < .001). In addition, the glenoid of the ASI patients was more anteverted compared with that of controls (P = .001). There was no statistical difference in half the measurements between the bilateral shoulder joints in patients with ASI. Conclusion: In this study, glenohumeral geometric differences were found between ASI patients and healthy control participants. Glenoid curvature and conformity index, based on bilateral comparisons of affected and contralateral shoulders, appear inherent and may predict ASI risk.

Efficacy of DAIR in managing Candida parapsilosis-infected total knee arthroplasty with five-year follow-up: A case report and review of literature.

RATIONALE: Fungal periprosthetic joint infections (fPJIs) are relatively uncommon, accounting for approximately 1% of all PJIs. Revision surgery is typically recommended for fungal infections; however, the physical and financial impact on patients is significant. In this report, we present a case of fPJI successfully treated with debridement, antibiotics, and implant retention (DAIR) with a favorable outcome over a 5-year period. PATIENT CONCERN: A 56-year-old male patient presented with a non-healing surgical incision 1 week after undergoing primary total knee arthroplasty on the right side. DIAGNOSIS: Microbiological culture of the wound effusion identified Candida parapsilosis. Postoperatively, the patient exhibited a significant decrease in serum albumin levels and poor glycemic control. Both C-reactive protein and erythrocyte sedimentation rate were elevated. INTERVENTIONS: A comprehensive DAIR procedure was performed, along with continuous closed irrigation using fluconazole for 1 week. The patient received intravenous voriconazole for 4 weeks, followed by oral fluconazole for an additional 3 months. OUTCOMES: At 1- and 5-year follow-up appointments, the patient C-reactive protein and erythrocyte sedimentation rate levels were within normal limits, and there was no evidence of swelling, erythema, or tenderness in the right knee joint, indicating no signs of infection. LESSONS: DAIR is an effective treatment for early fPJIs, and continuous closed irrigation may provide specific advantages. The patient nutritional status plays a crucial role in the management of periprosthetic infections.

Biological Hyperthermia-Inducing Nanoparticles for Specific Remodeling of the Extracellular Matrix Microenvironment Enhance Pro-Apoptotic Therapy in Fibrosis.

The extracellular matrix (ECM) is a major driver of fibrotic diseases and forms a dense fibrous barrier that impedes nanodrug delivery. Because hyperthermia causes destruction of ECM components, we developed a nanoparticle preparation to induce fibrosis-specific biological hyperthermia (designated as GPQ-EL-DNP) to improve pro-apoptotic therapy against fibrotic diseases based on remodeling of the ECM microenvironment. GPQ-EL-DNP is a matrix metalloproteinase (MMP)-9-responsive peptide, (GPQ)-modified hybrid nanoparticle containing fibroblast-derived exosomes and liposomes (GPQ-EL) and is loaded with a mitochondrial uncoupling agent, 2,4-dinitrophenol (DNP). GPQ-EL-DNP can specifically accumulate and release DNP in the fibrotic focus, inducing collagen denaturation through biological hyperthermia. The preparation was able to remodel the ECM microenvironment, decrease stiffness, and suppress fibroblast activation, which further enhanced GPQ-EL-DNP delivery to fibroblasts and sensitized fibroblasts to simvastatin-induced apoptosis. Therefore, simvastatin-loaded GPQ-EL-DNP achieved an improved therapeutic effect on multiple types of murine fibrosis. Importantly, GPQ-EL-DNP did not induce systemic toxicity to the host. Therefore, the nanoparticle GPQ-EL-DNP for fibrosis-specific hyperthermia can be used as a potential strategy to enhance pro-apoptotic therapy in fibrotic diseases.

Clodronate-nintedanib-loaded exosome-liposome hybridization enhances the liver fibrosis therapy by inhibiting Kupffer cell activity.

Liver fibrosis therapy remains limited due to the inefficiency of drug delivery and inflammation induced by Kupffer cells. In this study, an exosome-liposome hybrid drug delivery system (LIEV) was developed to increase the efficacy of clodronate (CLD)-inhibition of Kupffer cells and to effectively deliver nintedanib (NIN) to liver fibroblasts to ensure enhanced anti-fibrosis therapy. CLD and NIN co-loaded LIEV (CLD/NIN@LIEV) exerted non-specific inhibition of phagocytosis by Kupffer cells, reduced inflammatory cytokines, and showed homologous homing properties mediated by fibroblast-derived exosomes, thereby achieving superior antifibrotic effects in a CCl4-induced fibrosis mouse model by inhibiting the proliferation of fibroblasts. Furthermore, the inhibited Kupffer cells regenerated within 10 days after dosage withdrawal. Unlike carrier-free NIN treatment, CLD/NIN@LIEV induced a marked decrease in liver enzymes, indicating improved safety and anti-fibrosis efficacy. These results indicate its great potential for treatment with the combined anti-fibrosis agent and Kupffer cell inhibition strategies to enhance the liver fibrosis therapy.

Clodronate-loaded liposomal and fibroblast-derived exosomal hybrid system for enhanced drug delivery to pulmonary fibrosis.

Pulmonary fibrosis is a rapidly progressive and fatal fibrotic lung disease with high mortality and morbidity. However, pulmonary fibrosis therapy in the clinic has been limited by poor selectivity and inefficiency of drug delivery to fibroblasts. Herein, a clodronate (CLD)-loaded liposome and fibroblast-derived exosome (EL-CLD) hybrid drug delivery system with non-specific phagocytosis inhibition and fibroblast homing properties, was designed for the treatment of pulmonary fibrosis. EL-CLD effectively depleted Kupffer cells via apoptosis by passive targeting after intravenous injection, and thus significantly reduced accumulation in the liver. Notably, the EL-CLD hybrid system preferentially accumulated in the fibrotic lung, and significantly increased penetration inside pulmonary fibrotic tissue by targeted delivery due to the specific affinity for fibroblasts of the homologous exosome. Nintedanib (NIN), an anti-fibrotic agent used to treat pulmonary fibrosis, was loaded in the EL-CLD system, and achieved a remarkable improvement in curative effects. The enhanced therapeutic efficacy of NIN was a result of enhanced pulmonary fibrotic tissue accumulation and delivery, combined with a diminished macrophage-induced inflammatory response. Hence, the EL-CLD hybrid system acts as an efficient carrier for pulmonary anti-fibrotic drug delivery and should be developed as an efficient fibroblast specific therapy.