Biomimetic platelet-like nanoparticles enhance targeted hepatocellular carcinoma therapy.

Curcumin (CUR) is a promising natural product for hepatocellular carcinoma (HCC) therapy. However, its clinical application has been limited by some issues such as rapid clearance and inadequate tumor accumulation. To address these drawbacks, we developed platelet membrane-coated CUR-loaded PLGA nanoparticles (PCPNPs). In this work, due to the bioinspired strategy, the PCPNPs exhibited immune evasion, prolonged circulation, and improved accumulation at tumor sites compared to the traditional CUR formulation. The superior tumor targeting of PCPNPs was likely due to the interactions between platelet P-selectin and tumoral CD44. Furthermore, both in vitro and in vivo assays revealed that the PCPNPs showed outstanding anticancer efficacy without obvious toxicity. Therefore, PCPNPs represent a biosafe and promising anti-tumor strategy, overcoming the limitations associated with CUR. These findings not only contribute to the advancement of natural compound nano-formulation but also open new avenues for targeted cancer treatment.

Pan-analysis reveals CACYBP to be a novel prognostic and predictive marker for multiple cancers.

OBJECTIVES: Cancer has emerged as a global issue in terms of public health care and treatment. The significance of calcyclin binding protein (CACYBP) in various neoplasms suggests that it may serve as a novel biomarker for numerous types of human tumors. METHODS: Our research investigated the differences in CACYBP expression between cancer tissues and normal tissues using a total of 18,787 samples from multiple centers. To explore the prognostic factor of CACYBP in cancers, we utilized Cox regression analysis and Kaplan-Meier curves. We also conducted Spearman's rank correlation analyses to determine the associations of CACYBP expression with the immune microenvironment, etc. Additionally, we applied gene set enrichment analysis to explore the underlying mechanisms of CACYBP in cancers. A partial validation of CacyBP expression in cancer tissues was performed through lung adenocarcinoma samples using Western blotting and paired t-test. RESULTS: Compared to normal tissues, CACYBP exhibited high expression levels in 14 cancer types, including breast invasive carcinoma, and low expression levels in six cancers, including glioblastoma multiforme (P < 0.05). CACYBP expression was found to be significantly associated with the prognosis of 13 cancers, including adrenocortical carcinoma (P < 0.05). CACYBP demonstrated a robust ability to distinguish 15 cancers, including cholangiocarcinoma, from their control samples (area under the curve > 0.8). Furthermore, CACYBP expression was correlated with tumor mutational burden, microsatellite instability, and immune infiltration levels, indicating its potential as an exciting target for cancer treatment. CACYBP may exert its effects on several signaling pathways, including cytokine-cytokine receptor interaction, in various cancers. Compared with paired adjacent specimens, the expression level of CacyBP protein was up-regulated in lung adenocarcinoma specimens (P < 0.05), partially validating the increased expression of CACYBP in cancers. CONCLUSIONS: CACYBP has the potential to serve as a novel prognostic and predictive marker for multiple human cancers.

Exploring thermal isomerisation in gas chromatography analyses using natural pyrethrins: Comparison of comprehensive two-dimensional and one-dimensional gas chromatography.

This study aims to assess and qualitatively compare the visual presentation of chromatographic data from the isomerisation of natural pyrethrins - a group of pesticides derived from Chrysanthemum flowers - using one-dimensional gas chromatography (1DGC) and comprehensive two-dimensional gas chromatography (GC×GC). Molecular structural changes, such as thermal isomerisation in this case, occur during gas chromatography injection and separation, to provide characteristic patterns which may not be routinely recognised on the 1D chromatogram. To demonstrate the influence of analytical method parameters on isomerisation processes, variations in oven temperature (isothermal vs. temperature programmed analysis), inlet mode (split vs. splitless), inlet temperature, and carrier gas flow rate were investigated. Increasing oven temperature was the most significant factor affecting isomerisation. Splitless injection mode and increasing inlet temperature promoted isopyrethrin formation, while the effect of inlet temperature appeared minimal with a split injection technique, most likely due to the short residence time in the inlet. Increased carrier gas flow rates in a temperature programmed analysis reduced retention time and minimised isomerisation. The unique presentation of isopyrethrin peaks on a GC×GC contour plot allows for facile recognition of isomerisation especially at low concentrations, simplifies chromatogram interpretation, and aids in analyte identification. It also confirms that the isomerisation process is irreversible since the pyrethrin I and II compounds are absent throughout the bridge formation. These benefits support the use of GC×GC over 1DGC to study isomerisation. Additionally, due to limited data in the literature, Kováts retention indices and linear retention indices of the natural pyrethrins, including isopyrethrins, were experimentally determined on four columns: DB-5 ms UI, Rxi-17Sil MS, SLB-IL60i, and SLB-IL111i.

Xanthotoxin, a novel inducer of platelet formation, promotes thrombocytopoiesis via IL-1R1 and MEK/ERK signaling.

BACKGROUND: Thrombocytopenia is a common hematological disease caused by many factors. It usually complicates critical diseases and increases morbidity and mortality. The treatment of thrombocytopenia remains a great challenge in clinical practice, however, its treatment options are limited. In this study, the active monomer xanthotoxin (XAT) was screened out to explore its medicinal value and provide novel therapeutic strategies for the clinical treatment of thrombocytopenia. METHODS: The effects of XAT on megakaryocyte differentiation and maturation were detected by flow cytometry, Giemsa and phalloidin staining. RNA-seq identified differentially expressed genes and enriched pathways. The signaling pathway and transcription factors were verified through WB and immunofluorescence staining. Tg (cd41: eGFP) transgenic zebrafish and mice with thrombocytopenia were used to evaluate the biological activity of XAT on platelet formation and the related hematopoietic organ index in vivo. RESULTS: XAT promoted the differentiation and maturation of Meg-01 cells in vitro. Meanwhile, XAT could stimulate platelet formation in transgenic zebrafish and recover platelet production and function in irradiation-induced thrombocytopenia mice. Further RNA-seq prediction and WB verification revealed that XAT activates the IL-1R1 target and MEK/ERK signaling pathway, and upregulates the expression of transcription factors related to the hematopoietic lineage to promote megakaryocyte differentiation and platelet formation. CONCLUSION: XAT accelerates megakaryocyte differentiation and maturation to promote platelet production and recovery through triggering IL-1R1 and activating the MEK/ERK signaling pathway, providing a new pharmacotherapy strategy for thrombocytopenia.

Saturated fatty acids dampen the immunogenicity of cancer by suppressing STING.

Oncogenes destabilize STING in epithelial cell-derived cancer cells, such as head and neck squamous cell carcinomas (HNSCCs), to promote immune escape. Despite the abundance of tumor-infiltrating myeloid cells, HNSCC presents notable resistance to STING stimulation. Here, we show how saturated fatty acids in the microenvironment dampen tumor response to STING stimulation. Using single-cell analysis, we found that obesity creates an IFN-I-deprived tumor microenvironment with a massive expansion of suppressive myeloid cell clusters and contraction of effector T cells. Saturated fatty acids, but not unsaturated fatty acids, potently inhibit the STING-IFN-I pathway in HNSCC cells. Myeloid cells from obese mice show dampened responses to STING stimulation and are more suppressive of T cell activation. In agreement, obese hosts exhibited increased tumor burden and lower responsiveness to STING agonist. As a mechanism, saturated fatty acids induce the expression of NLRC3, depletion of which results in a T cell inflamed tumor microenvironment and IFN-I-dependent tumor control.

Curcumin-Loaded Platelet Membrane Bioinspired Chitosan-Modified Liposome for Effective Cancer Therapy.

Cancer is a serious threat to human health, and chemotherapy for cancer is limited by severe side effects. Curcumin (CUR) is a commonly used natural product for antitumor treatment without safety concerns. However, low bioavailability and poor tumor accumulation are great obstacles for its clinical application. Our previous research has demonstrated that platelet membrane-camouflaged nanoparticles can efficiently ameliorate the in vivo kinetic characteristics and enhance the tumor affinity of payloads. Nevertheless, the antitumor efficiency of this formulation still needs to be thoroughly investigated, and its drug release behavior is limited. Herein, CUR-loaded platelet membrane bioinspired chitosan-modified liposome (PCLP-CUR) was constructed to improve CUR release. PCLP-CUR was shown to have long retention time, improved bioavailability, strong tumor targeting capacity and effective cellular uptake. The incorporation of chitosan enabled PCLP-CUR to release cargoes quickly under mild acidic tumor conditions, leading to more complete drug release and favoring subsequent treatment. Both in vitro and in vivo investigations showed that PCLP-CUR could significantly enhance the anticancer efficacy of CUR with minimal side effects through biomimetic membrane and chitosan modification. In summary, this developed delivery system can provide a promising strategy for tumor-targeting therapy and phytochemical delivery.

The combination of machine learning and transcriptomics reveals a novel megakaryopoiesis inducer, MO-A, that promotes thrombopoiesis by activating FGF1/FGFR1/PI3K/Akt/NF-κB signaling.

Radiation-induced thrombocytopenia (RIT) occurs widely and causes high mortality and morbidity in cancer patients who receive radiotherapy. However, specific drugs for treating RIT remain woefully inadequate. Here, we first developed a drug screening model using naive Bayes, a machine learning (ML) algorithm, to virtually screen the active compounds promoting megakaryopoiesis and thrombopoiesis. A natural product library was screened by the model, and methylophiopogonanone A (MO-A) was identified as the most active compound. The activity of MO-A was then validated in vitro and showed that MO-A could markedly induce megakaryocyte (MK) differentiation of K562 and Meg-01 cells in a concentration-dependent manner. Furthermore, the therapeutic action of MO-A on RIT was evaluated, and MO-A significantly accelerated platelet level recovery, platelet activation, megakaryopoiesis, MK differentiation in RIT mice. Moreover, RNA-sequencing (RNA-seq) indicated that the PI3K cascade was closely related to MK differentiation induced by MO-A. Finally, experimental verification demonstrated that MO-A obviously induced the expression of FGF1 and FGFR1, and increased the phosphorylation of PI3K, Akt and NF-κB. Blocking FGFR1 with its inhibitor dovitinib suppressed MO-A-induced MK differentiation, and PI3K, Akt and NF-κB phosphorylation. Similarly, inhibition of PI3K-Akt signal pathway by its inhibitor LY294002 suppressed MK differentiation, and PI3K, Akt and NF-κB phosphorylation induced by MO-A. Taken together, our study provides an efficient drug discovery strategy for hematological diseases, and demonstrates that MO-A is a novel countermeasure for treating RIT through activation of the FGF1/FGFR1/PI3K/Akt/NF-κB signaling pathway.

Fabrication, Optimization, and Evaluation of Paclitaxel and Curcumin Coloaded PLGA Nanoparticles for Improved Antitumor Activity.

Codelivery of chemotherapeutic drugs in nanoparticles can enhance the therapeutic effects against tumors. However, their anticancer properties and physiochemical characteristics can be severely influenced by many formulation parameters during the preparation process. It is a complicated development phase to select the optimal parameters for preparation of nanoparticles based on the commonly used one single parameter method, which consumes a lot of money, time, and effort, and sometimes even fails. Therefore, the statistical analysis based on Box-Behnken design (BBD) has attracted much attention in bioengineering fields because it can illustrate the influence of parameters, build mathematical models, and predict the optimal combinational factors in a decreased number of experiments. In this study, we used a three-factor three-level BBD design to optimize the preparation of poly(lactic-co-glycolic acid) (PLGA) nanoparticles coloaded with two anticancer drugs curcumin and paclitaxel (PLGA-CUR-PTX nanoparticles). The surfactant concentration, polymer concentration, and oil-water ratio were selected as independent variables. An optimized model of the formulation for PLGA-CUR-PTX nanoparticles was validated. The optimal nanoparticles possessed a uniform spherical shape, with an average size of 99.94 nm, and the drug encapsulation efficiencies of CUR and PTX were 63.53 and 80.64%, respectively. The drug release from nanoparticles showed a biphasic release behavior, with a release mechanism via diffusion and fundamentally quasi-Fickian diffusion. The optimized nanoparticles demonstrated an enhanced cytotoxicity effect with lower IC50 values to 4T1 and MCF-7 breast cancer cell lines compared to free drugs. In summary, BBD optimization of CUR and PTX coloaded nanoparticles yielded a favorable drug carrier that holds potential as an alternative treatment for anticancer therapy.

Novel chemical-structure TPOR agonist, TMEA, promotes megakaryocytes differentiation and thrombopoiesis via mTOR and ERK signalings.

BACKGROUND: Non-peptide thrombopoietin receptor (TPOR) agonists are promising therapies for the mitigation and treatment of thrombocytopenia. However, only few agents are available as safe and effective for stimulating platelet production for thrombocytopenic patients in the clinic. PURPOSE: This study aimed to develop a novel small molecule TPOR agonist and investigate its underlying regulation of function in megakaryocytes (MKs) differentiation and thrombopoiesis. METHODS: A potential active compound that promotes MKs differentiation and thrombopoiesis was obtained by machine learning (ML). Meanwhile, the effect was verified in zebrafish model, HEL and Meg-01 cells. Next, the key regulatory target was identified by Drug Affinity Responsive Target Stabilization Assay (DARTS), Cellular Thermal Shift Assay (CETSA), and molecular simulation experiments. After that, RNA-sequencing (RNA-seq) was used to further confirm the associated pathways and evaluate the gene expression induced during MK differentiation. In vivo, irradiation (IR) mice, C57BL/6N-TPORem1cyagen (Tpor-/-) mice were constructed by CRISPR/Cas9 technology to examine the therapeutic effect of TMEA on thrombocytopenia. RESULTS: A natural chemical-structure small molecule TMEA was predicted to be a potential active compound based on ML. Obvious phenotypes of MKs differentiation were observed by TMEA induction in zebrafish model and TMEA could increase co-expression of CD41/CD42b, DNA content, and promote polyploidization and maturation of MKs in HEL and Meg-01 cells. Mechanically, TMEA could bind with TPOR protein and further regulate the PI3K/AKT/mTOR/P70S6K and MEK/ERK signal pathways. In vivo, TMEA evidently promoted platelet regeneration in mice with radiation-induced thrombocytopenia but had no effect on Tpor-/- and C57BL/6 (WT) mice. CONCLUSION: TMEA could serve as a novel TPOR agonist to promote MKs differentiation and thrombopoiesis via mTOR and ERK signaling and could potentially be created as a promising new drug to treat thrombocytopenia.

Bioinspired Platelet-like Nanovector for Enhancing Cancer Therapy via P-Selectin Targeting.

Cancer is a major threat to the health of humans. Recently, various natural products including curcumin (CCM) have attracted enormous interest for efficacious cancer therapy. However, natural therapeutic agents still encounter certain challenges such as rapid clearance, low bioavailability, and poor tumor targeting. Recently, the platelet membrane (PM) camouflaged nanoparticle has provided a promising solution for cancer targeting therapy. Nevertheless, only limited efforts have been dedicated to systematically explore the mechanism of affinity between PM bioinspired nanoparticles and various tumor cells. Herein, a CCM-encapsulated platelet membrane biomimetic lipid vesicle (CCM@PL) with a size of 163.2 nm, zeta potential of -31.8 mV and encapsulation efficiency of 93.62% was developed. The values of the area under the concentration-time curve and mean residence time for CCM@PL were 3.08 times and 3.04 times those of CCM, respectively. Furthermore, this PM biomimetic carrier showed an excellent affinity against Huh-7, SK-OV-3 and MDA-MB-231 cell lines due to the biomolecular interaction between P-selectin on the PM and tumoral CD44 receptors. In addition, CCM@PL displayed enhanced cytotoxicity compared with free CCM and the synthetic formulation. Overall, our results suggest that this developed PM biomimetic lipid nanovector has great potential for targeted cancer treatment and natural components delivery.

Targeting TLR2/Rac1/cdc42/JNK Pathway to Reveal That Ruxolitinib Promotes Thrombocytopoiesis.

BACKGROUND: Thrombocytopenia has long been considered an important complication of chemotherapy and radiotherapy, which severely limits the effectiveness of cancer treatment and the overall survival of patients. However, clinical treatment options are extremely limited so far. Ruxolitinib is a potential candidate. METHODS: The impact of ruxolitinib on the differentiation and maturation of K562 and Meg-01 cells megakaryocytes (MKs) was examined by flow cytometry, Giemsa and Phalloidin staining. A mouse model of radiation-injured thrombocytopenia (RIT) was employed to evaluate the action of ruxolitinib on thrombocytopoiesis. Network pharmacology, molecular docking, drug affinity responsive target stability assay (DARTS), RNA sequencing, protein blotting and immunofluorescence analysis were applied to explore the targets and mechanisms of action of ruxolitinib. RESULTS: Ruxolitinib can stimulate MK differentiation and maturation in a dose-dependent manner and accelerates recovery of MKs and thrombocytopoiesis in RIT mice. Biological targeting analysis showed that ruxolitinib binds directly to Toll Like Receptor 2 (TLR2) to activate Rac1/cdc42/JNK, and this action was shown to be blocked by C29, a specific inhibitor of TLR2. CONCLUSIONS: Ruxolitinib was first identified to facilitate MK differentiation and thrombocytopoiesis, which may alleviate RIT. The potential mechanism of ruxolitinib was to promote MK differentiation via activating the Rac1/cdc42/JNK pathway through binding to TLR2.

Macrophage cell membrane-based nanoparticles: a new promising biomimetic platform for targeted delivery and treatment.

Synthetic nanoparticles with surface bioconjugation are promising platforms for targeted therapy, but their simple biological functionalization is still a challenging task against the complex intercellular environment. Once synthetic nanoparticles enter the body, they are phagocytosed by immune cells by the immune system. Recently, the cell membrane camouflage strategy has emerged as a novel therapeutic tactic to overcome these issues by utilizing the fundamental properties of natural cells. Macrophage, a type of immune system cells, plays critical roles in various diseases, including cancer, atherosclerosis, rheumatoid arthritis, infection and inflammation, due to the recognition and engulfment function of removing substances and pathogens. Macrophage membranes inherit the surface protein profiles and biointerfacing properties of source cells. Therefore, the macrophage membrane cloaking can protect synthetic nanoparticles from phagocytosis by the immune cells. Meanwhile, the macrophage membrane can make use of the natural correspondence to accurately recognize antigens and target inflamed tissue or tumor sites. In this review, we have summarized the advances in the fabrication, characterization and homing capacity of macrophage membrane cloaking nanoparticles in various diseases, including cancers, immune diseases, cardiovascular diseases, central nervous system diseases, and microbial infections. Although macrophage membrane-camouflaged nanoparticles are currently in the fetal stage of development, there is huge potential and challenge to explore the conversion mode in the clinic.

Methyl Gallate Alleviates Acute Ulcerative Colitis by Modulating Gut Microbiota and Inhibiting TLR4/NF-κB Pathway.

Ulcerative colitis (UC) is a complex immune-mediated inflammatory disease. In recent years, the incidence of UC has increased rapidly, however, its exact etiology and mechanism are still unclear. Based on the definite anti-inflammatory and antibacterial activities of Sanguisorba officinalis L., we studied its monomer, methyl gallate (MG). In this study, we employed flow cytometry and detected nitric oxide production, finding MG regulated macrophage polarization and inhibited the expression of proinflammatory cytokines in vitro. MG also exhibited anti-inflammatory activity accompanying with ameliorating body weight loss, improving colon length and histological damage in dextran sulfate sodium-induced UC mice. Meanwhile, transcription sequencing and 16S rRNA sequencing analyzed the key signaling pathways and changes in the gut microbiota of MG for UC treatment, proving that MG could alleviate inflammation by regulating the TLR4/NF-κB pathway in vivo and in vitro. Additionally, MG altered the diversity and composition of the gut microbiota and changed the abundance of metabolic products. In conclusion, our results are the first to demonstrate that MG has obvious therapeutic effects against acute UC, which is related to macrophage polarization, improved intestinal flora dysbiosis and inhibition of TLR4/NF-κB signaling pathway, and MG may be a promising therapeutic agent for UC treatment.

Preparation and optimization of poly (lactic-co-glycolic acid) rod-shaped particles in nano size range for paclitaxel delivery.

Nanoparticle shape has been acknowledged as an important design parameter due to its influence on nanoparticle interaction with biological systems. However, there is lacking of simple and scalable preparation technique for drug loaded non-spherical polymeric nanoparticles for a long time, thus hindering the potential applications. Although our previous research has modified the traditional emulsion solvent evaporation technique by adding guest molecules to prepare non-spherical poly (lactic-co-glycolic acid) (PLGA) particles, it is difficult to obtain nano-sized rods with minor axis less than 200 nm, which may have great potential in cancer therapy. Herein, in present research, the two-step ESE method was used and optimized to prepare poly (lactic-co-glycolic acid) nanorods for paclitaxel delivery. Firstly, the single-factor experiment was used to screen the influence of multi-factors including type of guest molecules, concentration of guest molecules, emulsification method, surfactant concentration, oil volume, poly (lactic-co-glycolic acid) concentration on the size and shape to determine the range of variables; based on the above range, a multi-factor and multi-level orthogonal experiment was designed. The formula is evaluated by the rod fabrication yield and the aspect ratio of major axis to minor axis. The results showed that the yield of nanorods in the optimal formula was 99% and the aspect ratio was 5.35 ± 2.05 with the minor axis of 135.49 ± 72.66 nm, and major axis of 657.77 ± 307.63 nm. In addition, the anti-cancer drug paclitaxel was successfully encapsulated in PLGA nanorods by the same technique. Our results not only enrich the ESE technique for preparing small sized poly (lactic-co-glycolic acid) nanorods, but also envision the potential application of nanorods for targeted cancer therapy with the delivery of paclitaxel.

Apoptosis in megakaryocytes: Safeguard and threat for thrombopoiesis.

Platelets, generated from precursor megakaryocytes (MKs), are central mediators of hemostasis and thrombosis. The process of thrombopoiesis is extremely complex, regulated by multiple factors, and related to many cellular events including apoptosis. However, the role of apoptosis in thrombopoiesis has been controversial for many years. Some researchers believe that apoptosis is an ally of thrombopoiesis and platelets production is apoptosis-dependent, while others have suggested that apoptosis is dispensable for thrombopoiesis, and is even inhibited during this process. In this review, we will focus on this conflict, discuss the relationship between megakaryocytopoiesis, thrombopoiesis and apoptosis. In addition, we also consider why such a vast number of studies draw opposite conclusions of the role of apoptosis in thrombopoiesis, and try to figure out the truth behind the mystery. This review provides more comprehensive insights into the relationship between megakaryocytopoiesis, thrombopoiesis, and apoptosis and finds some clues for the possible pathological mechanisms of platelet disorders caused by abnormal apoptosis.

DMAG, a novel countermeasure for the treatment of thrombocytopenia.

BACKGROUND: Thrombocytopenia is one of the most common hematological disease that can be life-threatening caused by bleeding complications. However, the treatment options for thrombocytopenia remain limited. METHODS: In this study, giemsa staining, phalloidin staining, immunofluorescence and flow cytometry were used to identify the effects of 3,3'-di-O-methylellagic acid 4'-glucoside (DMAG), a natural ellagic acid derived from Sanguisorba officinalis L. (SOL) on megakaryocyte differentiation in HEL cells. Then, thrombocytopenia mice model was constructed by X-ray irradiation to evaluate the therapeutic action of DMAG on thrombocytopenia. Furthermore, the effects of DMAG on platelet function were evaluated by tail bleeding time, platelet aggregation and platelet adhesion assays. Next, network pharmacology approaches were carried out to identify the targets of DMAG. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to elucidate the underling mechanism of DMAG against thrombocytopenia. Finally, molecular docking simulation, molecular dynamics simulation and western blot analysis were used to explore the relationship between DAMG with its targets. RESULTS: DMAG significantly promoted megakaryocyte differentiation of HEL cells. DMAG administration accelerated platelet recovery and megakaryopoiesis, shortened tail bleeding time, strengthened platelet aggregation and adhesion in thrombocytopenia mice. Network pharmacology revealed that ITGA2B, ITGB3, VWF, PLEK, TLR2, BCL2, BCL2L1 and TNF were the core targets of DMAG. GO and KEGG pathway enrichment analyses suggested that the core targets of DMAG were enriched in PI3K-Akt signaling pathway, hematopoietic cell lineage, ECM-receptor interaction and platelet activation. Molecular docking simulation and molecular dynamics simulation further indicated that ITGA2B, ITGB3, PLEK and TLR2 displayed strong binding ability with DMAG. Finally, western blot analysis evidenced that DMAG up-regulated the expression of ITGA2B, ITGB3, VWF, p-Akt and PLEK. CONCLUSION: DMAG plays a critical role in promoting megakaryocytes differentiation and platelets production and might be a promising medicine for the treatment of thrombocytopenia.

Total hip arthroplasty using a combined anterior and posterior approach via a lateral incision in patients with ankylosed hips.

BACKGROUND: For most patients with severely ankylosed hips, traditional surgical approaches do not provide sufficient exposure during THAs. We report our experience with a combined anterior and posterior approach using a lateral incision for total hip arthroplasty (THA) in patients with severe, spontaneous bony hip ankylosis. METHODS: Between January 2004 and December 2008, patients with severe, spontaneous bony hip ankylosis underwent THA via a combined anterior and posterior approach using a lateral incision. RESULTS: We included 47 patients (76 hips) with a mean age of 53 (range 22-72) years in our study. All surgeries were successful, and no significant postoperative complications occurred. The mean operative duration was 1.5 (range 1.3-1.7) hours, and mean blood loss was 490 (range 450-580) mL. The mean duration of follow-up was 5.5 (range 2-11) years. Harris hip score improved from 53 to 88 points postoperatively, and the outcome was good to excellent in 88.37% of cases. Heterotopic ossification occurred in 6 hips, and infection, which resolved with antibiotics, occurred in 1 patient. CONCLUSION: This combined anterior and posterior approach to THA using a lateral incision in patients with severe, spontaneous ankylosis provides very good exposure, protects the abduction unit and results in good to excellent postoperative recovery.

CONTEXTE: Pour la plupart des patients atteints d'une grave ankylose de la hanche, les approches chirurgicales classiques n'exposent pas suffisamment l'articulation lors des interventions pour prothèse totale de la hanche (PTH). Nous faisons état de notre expérience d'une approche antéro-postérieure à l'aide d'une incision latérale pour la PTH chez des patients atteints d'une grave ankylose ostéoarticulaire spontanée de la hanche. MÉTHODES: Entre janvier 2004 et décembre 2008, nous avons effectué des interventions pour PTH par l'approche antéro-postérieure à l'aide d'une incision latérale chez des patients présentant une grave ankylose ostéoarticulaire spontanée de la hanche. RÉSULTANTS: Nous avons inclus dans notre étude 47 patients (76 hanches) âgés en moyenne de 53 (entre 22 et 72) ans. Toutes les interventions ont réussi et on n'a eu à déplorer aucune complication postopératoire significative. La durée moyenne de l'intervention a été de 1,5 (entre 1,3 et 1,7) heure et la perte de sang moyenne a été de 490 (entre 450 et 580) mL. La durée moyenne du suivi a été de 5,5 (entre 2 et 11) ans. Le score de Harris pour la hanche s'est amélioré, passant de 53 à 88 points après l'intervention, et les résultats ont été de bons à excellents dans 88,37 % des cas. On a observé une ossification hétérotopique dans 6 hanches, et 1 patient a présenté une infection traitée avec succès par antibiothérapie. CONCLUSIONS: Cette approche antéro-postérieure à l'aide d'une incision latérale pour la PTH chez des patients présentant une grave ankylose ostéoarticulaire spontanée offre une excellente visibilité. Elle protège le système d'abduction et permet un rétablissement postopératoire de bon à excellent.

Results of hip resurfacing for developmental dysplasia of the hip of Crowe type I and II.

BACKGROUND: Recently, the new generation of metal-on-metal total hip resurfacing arthroplasty is well known for preserving the proximal femoral bone stock, minimizing the risk of postoperative dislocation using large femoral heads, and expecting low wear of metal-on-metal articulation for longer prosthesis survival. It also has the advantage in biomechanical loading in the proximal femur. The osteoarthritis secondary to developmental dysplasia of the hip (DDH) has been the most common reason for total hip arthroplasty. Most of the patients are young and active, who require improved range of motion of the hip besides relief of the pain, even expect to resume the ability to run and jump after the joint arthroplasty, thus to be allowed an active lifestyle. The objective of the current study was to evaluate the early outcome of resurfacing arthroplasty for the mild DDH cases (Crowe type I and II). METHODS: Between September 2005 and May 2007, twenty-one consecutive patients (twenty-six hips) with the diagnosis of osteoarthritis secondary to DDH underwent metal-on-metal resurfacing arthroplasty. The average age at the time of surgery was 46.5 years (range, 37-59 years). Six patients (28.6%) were male and fifteen (71.4%) were female. Clinical and radiographic results were observed. The follow-up was performed at 6 weeks, 3, 6, 9 months and then yearly. RESULTS: All patients were followed for a mean of 18 months (9-29 months). During the follow-up period no complications, such as dislocation of hip joints, infection or femoral neck fracture occurred. The clinical outcomes, as rated with the Harris hip score, improved significantly compared with the preoperative ratings. The mean postoperative Harris hip score was 90.7, compared to 35.5 preoperatively. The radiographic analysis showed that all prostheses were fixed with no radiolucencies. All of the patients who had equal limb lengths preoperatively had equal lengths postoperatively. Of the nine patients with preoperative limb-length discrepancy of 0.8 to 1.2 cm, all regained equal limb length postoperatively. In addition the pain was nearly completely relieved, the range of motion was remarkably improved and no restriction was needed after operation regarding early exercise. CONCLUSIONS: The new generation of metal-on-metal resurfacing arthroplasty may be a reasonable option for DDH of the Crowe types I and II.