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2.
Chin Med J (Engl) ; 134(2): 164-172, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33410616

RESUMO

BACKGROUND: Aspirin has demonstrated safety and efficacy for venous thromboembolism (VTE) prophylaxis following total hip arthroplasty (THA); however, inconsistent dose regimens have been reported in the literature. This study aimed to evaluate and compare the safety and efficacy of 100 mg aspirin twice daily with rivaroxaban in VTE prophylaxis following THA. METHODS: Patients undergoing elective unilateral primary THA between January 2019 and January 2020 were prospectively enrolled in the study and randomly allocated to receive 5 weeks of VTE prophylaxis with either oral enteric-coated aspirin (100 mg twice daily) or rivaroxaban (10 mg once daily). Medication safety and efficacy were comprehensively evaluated through symptomatic VTE incidence, deep vein thrombosis (DVT) on Doppler ultrasonography, total blood loss (TBL), laboratory bloodwork, Harris hip score (HHS), post-operative recovery, and the incidence of other complications. RESULTS: We included 70 patients in this study; 34 and 36 were allocated to receive aspirin and rivaroxaban prophylaxis, respectively. No cases of symptomatic VTE occurred in this study. The DVT rate on Doppler ultrasonography in the aspirin group was not significantly different from that in the rivaroxaban group (8.8% vs. 8.3%, χ2 = 0.01, P = 0.91), confirming the non-inferiority of aspirin for DVT prophylaxis (χ2 = 2.29, P = 0.01). The calculated TBL in the aspirin group (944.9 mL [658.5-1137.8 mL]) was similar to that in the rivaroxaban group (978.3 mL [747.4-1740.6mL]) (χ2 = 1.55, P = 0.12). However, there were no significant inter-group differences in HHS at post-operative day (POD) 30 (Aspirin: 81.0 [78.8-83.0], Rivaroxaban: 81.0 [79.3-83.0], χ2 = 0.43, P = 0.67) and POD 90 (Aspirin: 90.0 [89.0-92.0], Rivaroxaban: 91.5 [88.3-92.8], χ2 = 0.77, P = 0.44), the incidence of bleeding events (2.9% vs. 8.3%, χ2 = 0.96, P = 0.33), or gastrointestinal complications (2.9% vs. 5.6%, χ2 = 1.13, P = 0.29). CONCLUSION: In terms of safety and efficacy, the prophylactic use of 100 mg aspirin twice daily was not statistically different from that of rivaroxaban in preventing VTE and reducing the risk of blood loss following elective primary THA. This supports the use of aspirin chemoprophylaxis following THA as a less expensive and more widely available option for future THAs. TRIAL REGISTRATION: Chictr.org, ChiCTR18000202894; http://www.chictr.org.cn/showproj.aspx?proj=33284.

3.
Acta Pharmacol Sin ; 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33495516

RESUMO

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by toxic aggregates of mutant huntingtin protein (mHTT) in the brain. Decreasing mHTT is a potential strategy for therapeutic purpose of HD. Valosin-containing protein (VCP/p97) is a crucial regulator of proteostasis, which regulates the degradation of damaged protein through proteasome and autophagy pathway. Since VCP has been implicated in pathogenesis of HD as well as other neurodegenerative diseases, small molecules that specifically regulate the activity of VCP may be of therapeutic benefits for HD patients. In this study we established a high-throughput screening biochemical assay for VCP ATPase activity measurement and identified gossypol, a clinical approved drug in China, as a novel modulator of VCP. Gossypol acetate dose-dependently inhibited the enzymatic activity of VCP in vitro with IC50 of 6.53±0.6 µM. We further demonstrated that gossypol directly bound to the interface between the N and D1 domains of VCP. Gossypol acetate treatment not only lowered mHTT levels and rescued HD-relevant phenotypes in HD patient iPS-derived Q47 striatal neurons and HD knock-in mouse striatal cells, but also improved motor function deficits in both Drosophila and mouse HD models. Taken together, gossypol acetate acted through a gain-of-function way to induce the formation of VCP-LC3-mHTT ternary complex, triggering autophagic degradation of mHTT. This study reveals a new strategy for treatment of HD and raises the possibility that an existing drug can be repurposed as a new treatment of neurodegenerative diseases.

4.
Arch Gynecol Obstet ; 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33471216

RESUMO

PURPOSE: Adenomyosis is a diffuse or localized disease. Our previous study has indicated that tanshinone IIA (TSIIA) inhibits the proliferation, migration, and induces apoptosis of ectopic endometrial stromal cells (EESCs) of adenomyosis. However, the complex molecular mechanism of TSIIA in adenomyosis remains unclear. The objective of this study was to explore the complex molecular mechanism of TSIIA on EESCs. METHODS: In our present study, we used the proteomics approach iTRAQ (isobaric tags for relative and absolute quantitation) combined with LC-MS/MS (liquid chromatography-mass spectrometry) to investigate changes in the protein profile of EESCs treated with TSIIA. Differential proteins were analyzed by employing bioinformatics tools and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. In TSIIA treated EESCs, the protein expression levels of TNFRSF10D, PLEKHM1, FECH, and TPM1A were detected by western blotting. RESULTS: Quantitative results revealed 267 significantly differential proteins in TSIIA pretreated EESCs. Gene Ontology (GO) analysis presented an overview of dysregulated proteins in the biological process (BP), cell component (CC), and molecular function (MF) categories. Interestingly, we observed that differential proteins in the extracellular matrix (ECM)-receptor interaction pathway and estrogen signaling pathway were all involved in the focal adhesion pathway, which plays essential roles in the TSIIA-mediated inhibition of EESC proliferation and migration. Furthermore, some significantly differential proteins, which may be potential targets for the treatment of adenomyosis in the future, were validated by western blotting. CONCLUSIONS: Our study provides a useful method to detect the detailed mechanism underlying the efficacy of TSIIA on EESCs.

5.
Eur J Med Chem ; 213: 113162, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33493826

RESUMO

Based on the previous research results of our research group, to further improve the anti-inflammatory activity of hesperetin, we substituted triazole at the 7-OH branch of hesperetin. We also evaluated the anti-inflammatory activity of 39 new hesperetin derivatives. All compounds showed inhibitory effects on nitric oxide (NO) and inflammatory factors in lipopolysaccharide-induced RAW264.7 cells. Compound d5 showed a strong inhibitory effect on NO (half maximal inhibitory concentration = 2.34 ± 0.7 µM) and tumor necrosis factor-α, interleukin (IL)-1ß, and (IL-6). Structure-activity relationships indicate that 7-O-triazole is buried in a medium-sized hydrophobic cavity that binds to the receptor. Compound d5 can also reduce the reactive oxygen species production and significantly inhibit the expression of inducible NO synthase and cyclooxygenase-2 through the nuclear factor-κB signaling pathway. In vivo results indicate that d5 can reduce liver inflammation in mice with acute liver injury (ALI) induced by CCI4. In conclusion, d5 may be a candidate drug for treating inflammation associated with ALI.

6.
Int Immunopharmacol ; 91: 107235, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33326919

RESUMO

Paeonol is a natural phenolic compound and isolated as an active ingredient from Moutan Cortex. Paeonol derivative-6 (DPF-6) is a derivative of paeonol improved in water solubility and bioavailability. Previous studies have reported that paeonol possesses a variety of pharmacological activities, such as antioxidant and anti-inflammatory properties. Moreover, we have previously verified that DPF-6 has anti-inflammatory effects. However, the role and fundamental mechanism of DPF-6 in acute liver injury (ALI) was still unclear. In this study, we indicated that DPF-6 inhibited inflammation and the expression of TNF-α, IL-6 and IL-1ß in liver tissues and LPS-mediated L-02 cells, concomitant with the upregulated expression of ZEB2. More importantly, it was demonstrated that overexpression of ZEB2 inhibited the expression level of TNF-α, IL-6 and IL-1ß in LPS-mediated L-02 cells. In contrast, knockdown of ZEB2 increased the expression level of TNF-α, IL-6 and IL-1ß in LPS-mediated L-02 cells. Further studies showed that ZEB2 inhibited the inflammation cytokine secretion via JNK signaling pathway in L-02 cells. Taken together, all the above results indicate that DPF-6 increased the expression of ZEB2, consequently inhibited inflammation cytokine secretion through JNK signaling pathway, which may be utilized as a potential anti-inflammation monomeric compound in the treatment of ALI.

7.
Carbohydr Polym ; 254: 117281, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33357857

RESUMO

Practical application of powder photocatalysts is far from satisfying due to their low photon utilization, inconvenient recovery and potential environmental risk. In this study, an easily recoverable, environmentally friendly and highly transparent floatable magnetic photocatalyst carrier was prepared based on biopolymer alginate and Fe3O4 particles. Further, three different types of photocatalysts were chosen as model semiconductor photocatalysts and loaded on the shell of the carriers. The freeze process facilitated the formation of internal cavities that enhanced floating ability and transparency of the spheres. Meanwhile, the excellent floating performance offered massive reaction sites for pollutants reacting with photocatalysts, O2 and photons on the air/water interface. Photodegradation results showed all three floatable hybrid photocatalysts exhibited enhanced photocatalytic efficiencies compared to the virgin photocatalysts. In short, the carrier can integrate excellent floating ability, environmental friendliness and full recycling with good stability, and it can greatly improve the photocatalytic efficiency of various powder semiconductor photocatalysts.

8.
Int Immunopharmacol ; 90: 107214, 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33278748

RESUMO

We previously revealed that the overexpression of synovial aquaporin 1 (AQP1) aggravated collagen-induced arthritis (CIA) in rats via regulating ß-catenin signaling. This study was to demonstrate the therapeutic effect of acetazolamide (AZ, an AQP1 inhibitor) on rat CIA and explored its underlying mechanisms. Paw swelling, arthritis index, pathological assessments, and serum levels of collagen type II (Col II) antibody, IL-1ß and TNF-α were measured to evaluate the anti-arthritic effect of AZ on rat CIA. Ki67 immunohistochemistry and TUNEL assay were performed to reveal the anti-proliferative and pro-apoptotic effects of AZ on synovial cells in vivo. The protein levels of apoptosis-related genes and Wnt/ß-catenin pathway key members were detected by western blot. We found that AZ treatment on CIA rats could inhibit paw swelling, reduce arthritis index, alleviate the pathologic changes of ankle joint and decrease the serum levels of Col II antibody, TNF-α and IL-1ß. AZ could reduce Ki67 expression and increase apoptosis index in CIA synovial tissues by reducing Bcl-2 protein level, increasing Bax and caspase 3 protein levels and normalizing Bcl-2/Bax ratio. Moreover, AZ could reduce the protein levels of Wnt1, ß-catenin, p-GSK-3ß (Ser9), c-myc, cyclin D1 and MMP9, while increase GSK-3ß protein level in CIA synovial tissues. Importantly, these mentioned effects of AZ (60 mg/kg) on CIA rats could be reversed by the combined use of lithium chloride (LiCl), an activator of Wnt/ß-catenin pathway. In short, AZ exerted potent anti-arthritic effects on CIA rats by inducing synovial apoptosis and inhibiting Wnt/ß-catenin pathway.

9.
Chem Biol Interact ; : 109350, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33307048

RESUMO

A series of 7-O-amide hesperetin derivatives were subjected to multi-target biological evaluation of anti-Alzheimer's disease. Most of the compounds showed good in vitro inhibitory activity against cholinesterase, of which compound 7c (7-O-(4-(morpholinoethyl)-acetamide) hesperetin) was the most effective anti-eqBuChE derivative (IC50 = 0.28 ± 0.05 µM) and exerted neuroprotective effects. Further biological evaluation found that compounds 4d, 4e and 7c showed strong antioxidant, anti-Aß self-aggregation and anti-neuroinflammatory activities. Compound 7c could inhibit the expression of iNOS and COX-2 proteins and prevent LPS-induced inflammatory response in BV2 cells. In addition, compound 7c could chelate biometal ions such as Cu2+ and Zn2+. In the vivo study, the MWM test confirmed that compound 7c could improve the cognitive impairment caused by scopolamine. In summary, the above studies have shown that the optimized compound 7c has great development potential as MTDL for the treatment of AD.

10.
Hepatol Int ; 14(6): 1034-1047, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33369707

RESUMO

BACKGROUND AND AIMS: Microvascular invasion (MVI) is a key pathological factor that severely affects the postoperative prognosis of patients with hepatocellular carcinoma (HCC). However, no MVI classification schemes based on standardized gross sampling protocols of HCC are available at present. METHODS: 119 HCC specimens were sampled at multiple sites (3-, 7-, and 13 points) for the optimum MVI detection rate. 16,144 resected HCCs were graded as M0, M1 or M2 by adopting three-tiered MVI grading (MVI-TTG) scheme based on the seven-point sampling protocol (SPSP). Survival analyses were performed on 2573 patients to explore the advantages of MVI-TTG. RESULTS: The MVI detection rate determined by SPSP was significantly higher than that determined by the 3-point sampling method (34.5% vs. 47.1%, p = 0.048), but was similar to that determined by the 13-point sampling method (47.1% vs. 51.3%, p = 0.517). Among 16,144 resected HCCs, the proportions of M0, M1 and M2 specimens according to SPSP were 53.4%, 26.2% and 20.4%, respectively. Postoperative survival analysis in 2573 HCC patients showed that the 3-year recurrence rates in M0, M1 and M2 MVI groups were 62.5%, 71.6% and 86.1%, respectively (p < 0.001), and the corresponding 3-year overall survival (OS) rates were 94.1%, 87.5% and 67.0%, respectively (p < 0.001). M1 grade was associated with early recurrence, while M2 grade was associated with both early and late recurrence. MVI-TTG had a larger area under the curve and net benefit rate than the two-tiered MVI grading scheme for predicting time to recurrence and OS. CONCLUSIONS: SPSP is a practical method to balance the efficacy of sampling numbers and MVI detection rates. MVI-TTG based on SPSP is a better prognostic predictor than the two-tiered MVI scheme. The combined use of SPSP and MVI-TTG is recommended for the routine pathological diagnosis of HCC.

11.
Nutr Cancer ; : 1-10, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33356605

RESUMO

The Geriatric Nutritional Risk Index (GNRI) is widely applied as a prognostic factor in different cancers. We aimed to analyze the prognostic value of the GNRI in 257 patients diagnosed with advanced non-small-cell lung cancer (NSCLC). Patients with GNRI >98, 92-98, and <92 were grouped into normal, low risk and moderate/high risk groups, respectively. There were 45.1% patients at risk for malnutrition. Kaplan-Meier survival curves indicated that patients with lower GNRI scores had a poorer overall survival (OS). Two-year OS for normal, low risk and moderate/high risk groups were 57.4%, 42.3% and 15.8%, respectively. In multivariate survival analysis, GNRI (<92), body mass index (BMI, ≥24 kg/m2), combined therapy, hemoglobin and neutrophil-to-lymphocyte ratio (NLR) were independent prognostic factors of OS. Stratifying by age groups, GNRI (<92), hemoglobin and NLR were independent prognostic factors of OS in patients aged <65 years. GNRI (<92), smoking, BMI (≥24 kg/m2) and platelet-to-lymphocyte ratio were independent prognostic factors of OS in patients aged ≥65 years. In conclusion, GNRI was a significant prognostic factor in advanced NSCLC patients regardless of age. A decreased GNRI may be considered as a clinical trigger for nutritional support in advanced NSCLC patients, though additional studies are still required to confirm the best cut-point.

12.
Lancet ; 396(10266): 1914, 2020 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-33308473
13.
Int J Biol Macromol ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33189756

RESUMO

Bone related-bacterial diseases including wound infections and osteomyelitis (OM) remain a serious problem accompanied with amputation in most severe cases. In this work, we report an exceptional effective antibacterial alginate aerogel, which consists of tigecycline (TGC) and octahedral Cu crystal as an organo-inorganic synergy platform for antibacterial and local infection therapy applications. The alginate aerogel could greatly prolong the release of copper ions and maintain effective antibacterial concentration over 18 days. The result of in-vitro experiments demonstrated that the alginate aerogel has an exceptional effective function on antibacterial activity. Cytotoxicity tests indicated that the alginate aerogel has low biological toxicity (average cell viability >75%). These remarkable results suggested that the alginate aerogel exhibits great potential for the treatment of OM, and has a prosperous future of application in bone tissue engineering.

14.
Sci Total Environ ; : 143142, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33168253

RESUMO

Modifying the surface of an anode can improve electroactive bacteria (EAB) enrichment, thereby enhancing the performance of the associated microbial electrochemical systems (MESs). In this study, biosynthetic FeS nanoparticles were used to modify the anode in MESs. The experimental results demonstrated that the stable maximum voltage of the FeS composited biochar (FeS/BC)-modified anode reached 0.72 V, which is 20% higher than that of the control. The maximum power density with the FeS/BC anode was 793 mW/m2, which is 46.31% higher than that obtained with the control (542 mW/m2). According to cyclic voltammetry (CV) analysis, FeS/BC facilitates the direct electron transfer between bacteria and the electrode. The biomass protein concentration of the FeS/BC anode was 841.75 µg/cm2, which is almost 1.5 times higher than that of the carbon cloth anode (344.25 µg/cm2); hence, FeS/BC modification can promote biofilm formation. The composition of Geobacter species on the FeS/BC anode (75.16%) was much higher than that on the carbon cloth anode (4.81%). All the results demonstrated that the use of the biosynthetic FeS/BC anode is an environmentally friendly and efficient strategy for enhancing the electroactive biofilm formation and EAB enrichment in MESs.

15.
Eur J Med Chem ; 209: 112874, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33017743

RESUMO

Pleiotropic intervention has prominent advantages for complex pathomechanisms, such as Alzheimer's disease (AD). In this study, a series of novel 3-(4-pyridyl)-5-(4- sulfamido-phenyl)-1,2,4-oxadiazole derivatives were designed and synthesized following the multitarget-directed ligand-based strategy. All compounds were evaluated for glycogen synthase kinase 3ß (GSK-3ß) inhibition and antineuroinflammatory and neuroprotective activities. Given that abnormal glucose metabolism plays an important role in AD occurrence and development, the effects of all compounds on glucose consumption in HepG2 cells was evaluated. Compounds 5e and 10b showed good dual potency in GSK-3ß inhibition (IC50: 5e = 1.52 µM, 10b = 0.19 µM) and antineuroinflammatory potency (IC50: 5e = 0.47 ± 0.64 µM, 10b = 6.94 ± 2.33 µM). The effect of compound 10b on glucose consumption was higher than that of positive drug metformin. These compounds exerted a certain neuroprotective effect. Compound 10b dramatically reduced Aß-induced Tau hyperphosphorylation, thus inhibiting GSK-3ß at the cellular level. Notably, compounds 5e and 10b exhibited good inhibitory effects on the formation of intracellular reactive oxygen species (ROS). Moreover, these compounds displayed proper blood-brain barrier permeability and lacked neurotoxicity up to 50 µM concentration. Finally, in vivo experiments revealed that compound 10b improved cognitive impairment in scopolamine-induced mouse models. Results indicated that compound 10b deserves further study as a multifunctional lead compound.

16.
Lab Chip ; 20(18): 3470, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32812612

RESUMO

Correction for 'High-throughput cell focusing and separation via acoustofluidic tweezers' by Mengxi Wu et al., Lab Chip, 2018, 18, 3003-3010, DOI: .

17.
Life Sci ; 258: 118228, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32781071

RESUMO

AIMS: Cyclin-dependent kinase 9 (CDK9) is a member of the CDK subfamily and plays a major role in the regulation of transcriptional elongation. It has attracted widespread attention as a therapeutic target for cancer. Here, we aimed to explore novel CDK 9 inhibitors by using a hybrid virtual screening strategy. MAIN METHODS: A hybrid virtual screening strategy was constructed with computer-aided drug design (CADD). First, compounds were filtered in accordance with Lipinski's rule of five and adsorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. Second, a 3D-QSAR pharmacophore model was built and used as a 3D query to screen the obtained hit compounds. Third, the hit compounds were subjected to molecular docking studies. Fourth, molecular dynamics (MD) simulations were performed on CDK9 in complex with the final hits to examine the structural stability. Finally, CDK9 kinase biochemical assay was performed to identify the biological activity of the hit compounds. KEY FINDINGS: Seven hit compounds were screened out. These hit compounds showed drug-like properties in accordance with Lipinski's rule of five and ADMET. Complexes involving the six hit compounds bound to CDK9 exhibited good structural stability in the MD simulation. Furthermore, these six hit compounds had strong inhibitory activity against CDK9 kinase. In particular, hit 3 showed the most promising activity with the percentage of 71%. SIGNIFICANCE: The six hit compounds may be promising novel CDK9 inhibitors, and the hybrid virtual screening strategy designed in this study provides an important reference for the design and synthesis of novel CDK9 inhibitors.


Assuntos
Quinase 9 Dependente de Ciclina/antagonistas & inibidores , Quinase 9 Dependente de Ciclina/metabolismo , Simulação de Acoplamento Molecular/métodos , Simulação de Dinâmica Molecular , Inibidores de Proteínas Quinases/metabolismo , Quinase 9 Dependente de Ciclina/química , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/fisiologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Estrutura Secundária de Proteína
18.
Acta Pharmacol Sin ; 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32796956

RESUMO

Grincamycins (GCNs) are a class of angucycline glycosides isolated from actinomycete Streptomyces strains that have potent antitumor activities, but their antitumor mechanisms remain unknown. In this study, we tried to identify the cellular target of grincamycin B (GCN B), one of most dominant and active secondary metabolites, using a combined strategy. We showed that GCN B-selective-induced apoptosis of human acute promyelocytic leukemia (APL) cell line NB4 through increase of ER stress and intracellular reactive oxygen species (ROS) accumulation. Using a strategy of combining phenotype, transcriptomics and protein microarray approaches, we identified that isocitrate dehydrogenase 1(IDH1) was the putative target of GCN B, and confirmed that GCNs were a subset of selective inhibitors targeting both wild-type and mutant IDH1 in vitro. It is well-known that IDH1 converts isocitrate to 2-oxoglutarate (2-OG), maintaining intracellular 2-OG homeostasis. IDH1 and its mutant as the target of GCN B were validated in NB4 cells and zebrafish model. Knockdown of IDH1 in NB4 cells caused the similar phenotype as GCN B treatment, and supplementation of N-acetylcysteine partially rescued the apoptosis caused by IDH1 interference in NB4 cells. In zebrafish model, GCN B effectively restored myeloid abnormality caused by overexpression of mutant IDH1(R132C). Taken together, we demonstrate that IDH1 is one of the antitumor targets of GCNs, suggesting wild-type IDH1 may be a potential target for hematological malignancies intervention in the future.

19.
Haemophilia ; 26(5): 882-890, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32741019

RESUMO

BACKGROUND: The characteristics of the haemophilia may endanger the patient with haemophilia (PWH) to higher ratio of wound complication, even lead to the refractory wound problem. The early wound complication in PWH has not been well studied in literature. METHODS: Between the period from 2002 to 2018, 250 patients underwent 323 elective orthopaedic surgical procedures for the treatment of haemophilic musculoskeletal disorders. The medical records were retrospectively reviewed. The patients were evaluated for postoperative wound complications within 30 days. Risk factors related to wound complications were further analysed. The patients underwent vacuum sealing drainage (VSD) for refractory wound healing problem were further analysed. RESULTS: Twenty-four patients of 250 patients experienced early wound complication within postoperative 30 days. The incidence of wound complication in the patients without preoperative infection was 6.5%. Positive inhibitor and surgery for pseudotumour were associated with higher rate of wound complication after logistic regression, with the odds ratios (OR) of 5.7 (95% CI, 1.08 to 30.3) and 4.9 (95% CI, 1.3 to 18.5), respectively. Eight patients underwent VSD treatment for refractory wound healing problem and recovered uneventfully. The total VSD treatment cycle was 2.25 (from 2 to 4). The average factor consumption was 26.1 IU kg-1  d-1 . The patients complicated with infection had higher, but not statistically significantly, treatment duration, factor consumption and peri-VSD total blood loss than the patients without infection. CONCLUSIONS: PWH had an incidence of 6.5% of early wound healing problem after elective orthopaedic surgery for musculoskeletal disorder in the present study. The presence of positive inhibitor and surgical procedure for haemophiliac pseudotumour are associated with higher incidence of wound healing problem. The VSD is an effective alternative for the treatment of refractory wound healing problem for PWH, especially for the patients complicated with infection.

20.
Haemophilia ; 26(5): 861-866, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32720447

RESUMO

INTRODUCTION: Patients with haemophilia are prone to haemophilic arthropathy (HA). For end-stage HA, total knee arthroplasty (TKA) is an effective procedure. However, limited data were available regarding complications of TKA in HA patients. AIM: To provide comprehensive comparisons of TKA complications among patients with osteoarthritis (OA), rheumatoid arthritis (RA) or HA. METHODS: The present study was a single-surgeon cohort study including patients who underwent TKAs for OA, HA or RA from January 1997 to December 2017. The information of patients was extracted from medical records and follow-up database. The primary outcome was complications. Potential risk factors of complications in HA patients were also evaluated. RESULTS: A total of 1515 patients with 2083 TKAs were selected following the criteria. The overall complication rate in the HA group was 21.79%, which was much higher than the OA or RA group (7.08% and 8.70%, respectively, P < .05). The dominate complications were prosthetic loosening and wound dehiscence. For HA, more complications occurred in the period more than 1 year after TKA when compared with OA (33.33% vs 11.43%, P = .028). Among the potential risk factors, patients with haemophilia B and severe haemophilia had significantly higher complication rates (P < .05 for both). CONCLUSION: When compared with OA or RA, HA patients had different characteristics on complications, including the higher complication rate, different complication distribution and later occurring time. In HA patients who underwent TKA, haemophilia B and severe haemophilia were risk factors of complications which should be paid more attention to.

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