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1.
Clin Biomech (Bristol, Avon) ; 70: 249-256, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31675680

RESUMO

BACKGROUND: This study aimed to provide a comprehensive investigation into factors influencing the thermal effect in robot assisted osteotomies utilizing a piezoelectric osteotome and to identify an optimal combination of factors that minimize the thermal effect in an orthogonal experimental design. METHODS: Fresh bovine cortical bone was cut under standardized conditions using a robot arm, a piezoelectric osteotome, and a cooling system. Temperature was monitored and the histological depth of osteocyte thermal necrosis was examined to quantify the thermal effect(s). Eighteen experimental trials were conducted according to the standard L18 (21 × 37) orthogonal design table to explore the roles of 6 factors: power of the piezoelectric osteotome, cutting depth, cutting speed, coolant type, coolant flow velocity, and coolant temperature. FINDINGS: Our data showed that coolant flow velocity, coolant temperature and cutting speed significantly influenced temperature (p < .05), while no significant temperature increase was identified relating to cutting depth, power of the piezoelectric osteotome and coolant type. The findings of histological osteocyte thermal necrosis correlated with the results of the temperature change. INTERPRETATION: Coolant flow velocity, coolant temperature and cutting speed were key factors influencing the thermal impact of the piezoelectric osteotome. With proper combination of these 3 factors, a piezoelectric osteotome is safe to use from a thermal perspective.

2.
ACS Appl Mater Interfaces ; 11(44): 41626-41639, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31596568

RESUMO

Regeneration of an injured meniscus continues to be a scientific challenge due to its poor self-healing potential. Tissue engineering provides an avenue for regenerating a severely damaged meniscus. In this study, we first investigated the superiority of five concentrations (0%, 0.5%, 1%, 2%, and 4%) of meniscus extracellular matrix (MECM)-based hydrogel in promoting cell proliferation and the matrix-forming phenotype of meniscal fibrochondrocytes (MFCs). We found that the 2% group strongly enhanced chondrogenic marker mRNA expression and cell proliferation compared to the other groups. Moreover, the 2% group showed the highest glycosaminoglycan (GAG) and collagen production by day 14. We then constructed a hybrid scaffold by 3D printing a wedge-shaped poly(ε-caprolactone) (PCL) scaffold as a backbone, followed by injection with the optimized MECM-based hydrogel (2%), which served as a cell delivery system. The hybrid scaffold (PCL-hydrogel) clearly yielded favorable biomechanical properties close to those of the native meniscus. Finally, PCL scaffold, PCL-hydrogel, and MFCs-loaded hybrid scaffold (PCL-hydrogel-MFCs) were implanted into the knee joints of New Zealand rabbits that underwent total medial meniscectomy. Six months postimplantation we found that the PCL-hydrogel-MFCs group exhibited markedly better gross appearance and cartilage protection than the PCL scaffold and PCL-hydrogel groups. Moreover, the regenerated menisci in the PCL-hydrogel-MFCs group had similar histological structures, biochemical contents, and biomechanical properties as the native menisci in the sham operation group. In conclusion, PCL-MECM-based hydrogel hybrid scaffold seeded with MFCs can successfully promote whole meniscus regeneration, and cell-loaded PCL-MECM-based hydrogel hybrid scaffold may be a promising strategy for meniscus regeneration in the future.

3.
Lung Cancer ; 137: 100-107, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31568886

RESUMO

OBJECTIVES: Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare subtype of primary lung cancer. Due to the lack of prospective studies, the optimal first-line chemotherapy regimens and survival outcomes remain unclear. MATERIALS AND METHODS: This real-world, retrospective study enrolled consecutive patients with unresectable pulmonary LELC. The survival outcomes, prognosis, and comparative efficacy of different chemotherapy regimens were investigated. RESULTS: In total, 127 patients were included in the analyses. The first-line chemotherapy regimens included gemcitabine plus platinum (GP, n = 19 [15.0%]), taxanes plus platinum (TP, n = 70 [55.1%]) and pemetrexed plus platinum (AP, n = 38 [30.0%]). 25 (19.7%) patients underwent palliative thoracic radiotherapy. 60 (47.2%) patients had detectable baseline Epstein-Barr virus (EBV) DNA. For the entire cohort, objective response was obtained in 41 patients (32.3%). Median progression-free survival (PFS) and overall survival (OS) were 7.7 months (95% CI, 6.6-8.8) and 36.7 months (95% CI, 30.9-42.5), respectively. Among the three chemotherapy regimens, GP achieved the highest response rate (GP, 63.2% vs. TP, 30.0% vs. AP, 21.1%; p = 0.005). Median PFS in the GP group (8.8 months) was also significantly longer than that in the TP group (7.9 months) and AP group (6.4 months) (p = 0.031). In the multivariate model, cycles of first-line chemotherapy (p < 0.001), palliative thoracic radiotherapy (p < 0.001), and chemotherapy regimens (p = 0.031) remained independent prognostic factors for PFS; while cycles of first-line chemotherapy (p = 0.002), baseline EBV DNA (p = 0.033) and palliative thoracic radiotherapy (p = 0.041) were significantly associated with OS. CONCLUSION: Gemcitabine-based chemotherapy and palliative thoracic radiotherapy are active in pulmonary LELC. These data provide added evidence for the similarity between pulmonary LELC and nasopharyngeal carcinoma in endemic area. Randomized controlled studies are needed to further define the standard-of-care for patients with advanced pulmonary LELC.

4.
J Biomech ; : 109415, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31630776

RESUMO

Intraoperative measurement of hip posture is the basis for assessing hip range of motion (ROM) and predicting postoperative functional limits allowable for activities of daily living. Although computer navigation for total hip arthroplasty (THA) has improved the accuracy of intraoperative ROM evaluation, it has not gained widespread popularity due to its complex and time-consuming protocol. We therefore developed an inertial measurement unit-based hip smart trial system (IMUHST) for intraoperative monitoring of hip posture. An in vitro validation experiment was conducted using bone models with a three-dimensional measurement model as the reference standard. The absolute mean error, Bland - Altman analysis and intra-class correlation coefficient demonstrated that the validity and reliability of this system meets the requirement for clinical application. Given that monitoring posture is the basis for evaluating the direction(s) of potential impingement, subluxation and dislocation, the IMUHST is a promising development direction of computer assisted surgery in THA.

5.
Orthop Surg ; 11(5): 811-818, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31549788

RESUMO

OBJECTIVE: To evaluate the mid-term clinical and radiographic results of revision total hip arthroplasty (THA) using jumbo cups in Chinese patients. METHODS: We retrospectively studied 61 patients (63 hips; 29 men [30 hips], 32 women [33 hips]) who underwent acetabular revision with jumbo cups between January 2001 and April 2016 at our institution. The mean age at the index operation was 59.4 ± 11.4 years. The mean body mass index of the patients was 24.9 ± 3.8 kg/m2 . Clinical evaluation was determined using the Harris hip score preoperatively and at follow up. Major complications (including instability, sepsis, and revision of the femoral or acetabular component) were recorded. Radiographic measurements included inclination and anteversion angles of the acetabular components, and the vertical and horizontal distances of the centers of rotation (V-COR and H-COR, respectively). In the 42 patients with normal contralateral hip joints, the postoperative V-COR and H-COR were compared between right and left sides. Their improvement in leg-length discrepancy (LLD) after revision THA was also evaluated. Cup survival was evaluated using the Kaplan-Meier analysis. Clinical and radiographic outcomes were analyzed. RESULTS: Mean follow up was 5.7 years (2-16 years). At the latest follow-up, the average Harris hip score (preoperative vs postoperative values) had improved from 46 to 83 (P < 0.001). No acetabular component was radiographically defined as loosened. Four hips (6.3%) had major complications: one hip was revised because of periprosthetic infection (at 3 months); one underwent femoral open reduction and internal fixation (with implant retention) because of a periprosthetic femoral fracture (at 13 months); one operated hip developed a deep infection (at 2.5 years), which was treated with antibiotics; one hip experienced recurrent dislocation (at 4.5 years). The average cup inclination angle was 40.8° ± 6.8° and the average anteversion angle was 14.9° ± 6.6°. Average V-COR decreased from 29.7 ± 10.4 mm to 22.3 ± 7.6 mm (P < 0.001). The average postoperative H-COR was 29.5 ± 3.7 mm compared with 30.8 ± 6.6 mm preoperatively (P = 0.145). Among the 42 patients with normal contralateral hips, the average postoperative V-COR were 22.2 ± 8.3 mm (operated side) and 14.0 ± 3.7 mm (contralateral side) (P < 0.001). LLD improved from -16.8 ± 17.1 mm to -5.6 ± 11.8 mm (P < 0.001). When failure was defined as any reoperation involving the hip, the mean 16-year hip survival was 96.8% (95% confidence interval [CI] 87.9%-99.2%). When defined as any hip reoperation or major complication, it was 92.7% (95%CI 81.2%-97.2%). CONCLUSION: Use of jumbo cups for revision THA resulted in excellent mid-term cup survival and helped restore the COR.

6.
Clin Biomech (Bristol, Avon) ; 70: 158-163, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31525656

RESUMO

BACKGROUND: The primary anti-rotational stability is critical to preventing cup tilting failure following revision total hip arthroplasty, but is frequently compromised by severe ischial bone loss. A novel technique of "inferior extended fixation" was introduced by securing a porous metal augment into the deficient ischium. This study evaluated the effect of this technique on primary anti-rotational stability in revision total hip arthroplasty. METHODS: Composite hemipelvis specimens, acetabular components and "lotus" augments were used to simulate total hip arthroplasty surgeries. Three different cementless operative settings of cup implantation were simulated: (1) native ischium without defects; (2) ischium with a defect not reconstructed; (3) ischial defect reconstructed with inferior extended fixation using a lotus augment. Lever-out testing was used to examine primary anti-rotational stability, which was measured as interface stiffness and yield moment. FINDINGS: Compared with the native ischium setting, the mean interface stiffness decreased by 53.1% in the ischial defect setting (p < 0.001). In the inferior extended fixation setting, the mean value was 110% greater than that in the ischial defect setting (p = 0.014), and comparable to that in the native ischium setting (p = 1). Similar results were observed for the yield moment (declined by 63.1%, p < 0.001; 200% higher, p < 0.001; and p = 0.395; respectively). INTERPRETATION: In revision total hip arthroplasty with severe ischial defects, inferior extended fixation with a lotus porous titanium augment restores anti-rotational stability of the acetabular component to the level of that with a native ischium, which provides the mechanical environment for bone ingrowth and prevents cup tilting failure.

7.
Knee ; 26(5): 1073-1079, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31402093

RESUMO

PURPOSE: This study aimed to evaluate the anthropometry of resected distal femurs in valgus knees at the level of standard cuts during total knee arthroplasty (TKA), and to compare these measurements to neutrally aligned knees. METHODS: Anteroposterior and mediolateral measurements of the distal femur were performed on three-dimensional computed tomography reconstructions of 57 valgus knees (34 intra-articular valgus and 23 juxta-articular valgus) and 40 neutrally aligned knees. The measured dimensions and calculated aspect ratios (ARs) were subsequently compared. RESULTS: Juxta-articular valgus knees had similar ARs when compared with neutrally aligned knees (1.14 ±â€¯0.06 vs. 1.12 ±â€¯0.05, P = 0.103). However, intra-articular valgus knees had smaller ARs (1.09 ±â€¯0.07) when compared with juxta-articular valgus (P = 0.002) or neutrally aligned knees (P = 0.023). CONCLUSION: Different origins of valgus deformity in the femur can significantly affect the AR values on the resected surface of the distal femur. Pre-operative evaluation of a valgus deformity may assist in estimating the morphology of the resected distal femur during TKA.

8.
J Immunother Cancer ; 7(1): 179, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300050

RESUMO

BACKGROUND: Immune cells play a key role in cancer progression and treatment. It is unclear whether the clinicopathologic characteristics and blood indexes of colorectal cancer (CRC) patients could predict immune cell concentrations in the tumor microenvironment. METHODS: CRC patients with detailed data and tumor tissue who visited Sun Yat-sen University Cancer Center between April 1, 2004, and September 1, 2017, were enrolled. The densities of CD3+ and CD8+ T cells examined by immunohistochemistry in both the core of the tumor (CT) and the invasive margin (IM) were summed as the Immunoscore. The relationships between the Immunoscore and clinicopathologic characteristics and blood indexes, including tumor biomarkers (carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9)), inflammatory markers (lactate dehydrogenase (LDH), C-reactive protein (CRP), albumin (ALB), neutrophils, lymphocytes, monocytes, platelets, NLR (neutrophil-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio) and LMR (lymphocyte-to-monocyte ratio)) and lipid metabolism markers (cholesterol (CHO), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB)), were analyzed using SPSS. RESULTS: Older patients had lower CD3+ and CD8+ T cell expression in the IM and a lower Immunoscore than did younger patients. CD8+ T cell expression in the IM and the Immunoscore were lower in right-side tumors than in left-sided tumors. High CD8+ T cell expression in the CT was found in the T4 stage group. The higher the CEA level in the blood, the fewer CD8+ T cells were in the CT. Either fewer monocytes or a higher LMR in the blood, the larger number of CD3+ T cells in the CT. The more ApoA1 was in the blood, the more CD3+ T cells were in both the CT and the IM. CONCLUSION: Age, T stage, tumor location, CEA, monocytes, LMR and ApoA1 could reflect immune cells infiltrating the tumor microenvironment of CRC.

9.
Mol Med Rep ; 20(2): 1725-1735, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31257504

RESUMO

MicroRNAs (miRNAs) have been found to play important regulatory roles in certain neurodegenerative diseases. The aim of the present study was to investigate the effect of miRNA­153 (miR­153) on the neural differentiation of HT­22 cells. Overexpression of miR­153 induced the differentiation of HT­22 cells, increasing the number of protrusions and branches, reducing the S phase distribution of the cell cycle, and attenuating the cell proliferation rate as determined using the Cell Counting Kit­8 assay. Furthermore, miR­153 increased the expression of neuron­specific γ­enolase (NSE), neuronal nuclei (NeuN), and N­ethylmaleimide­sensitive fusion attachment protein 23 (SNAP23) and SNAP25 at the transcriptional and protein level by PCR and western blot analysis. Moreover, miR­153 caused obvious upregulation of peroxiredoxin 5 (PRX5), which has been found to protect neural cells from death and apoptosis. miR­153 promoted neural differentiation and protected neural cells by upregulating the neuron markers γ­enolase, neuronal nuclei, and the functional proteins SNAP23, SNAP25 and PRX5. Therefore, miR­153 may be a potential target for the treatment of certain neurodegenerative diseases.

10.
Orthop Traumatol Surg Res ; 105(5): 967-974, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31227461

RESUMO

BACKGROUND: With increasing recognition of the importance of biofilm formation in the pathogenesis of periprosthetic joint infection (PJI), a push towards finding solutions to prevent PJI via surface modification of prostheses is occurring. Unlike the promising in vitro antimicrobial effects of these surface modifications, the preclinical and clinical prophylactic effects vary and are debated. Therefore, we performed this systematic review to answer: (1) what kinds of methods of surface modification are used in preclinical and clinical studies to prevent PJI, (2) whether these modifications are effective to prevent PJI. METHODS: Electronic searches were performed using PubMed, Embase and the Cochrane library databases up to and including December 2017 with predetermined criteria: (1) in vivo studies with (2) surface modification for prophylactic effects against infection. Both animal studies and clinical trials were included. Data were extracted and presented systematically. RESULTS: Overall, 21 studies were included. Among these, fourteen were carried out in animal models and seven were clinical studies. In the animal studies, six used antibiotics and six silver modifications, while copper and Cationic Steroidal Antimicrobial-13 were each used for one study. In the seven clinical studies targeting patients with high infection risk, five of them focused on silver-coated prostheses and the remaining two studied iodine-coated implants. In all of the animal studies, when compared with the control group, the surface modified groups had a lower infection risk (RR ranging from 0 to 0.71). Clinical studies using silver-coated prostheses also demonstrated a lower infection risk (RR ranging from 0.24 to 0.70), while iodine-coated implants showed a 0% and 5% incidence of PJI in the two case series included. DISCUSSION: The results from the publications included in this review indicate that surface modification, especially antibiotic and silver modifications, are helpful preventing PJI in both preclinical animal models and in clinical trials. LEVEL OF EVIDENCE: III, systematic review of level III retrospective comparative studies and level IV case series and animal experiments.

11.
J Immunother Cancer ; 7(1): 120, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31053172

RESUMO

Pembrolizumab monotherapy has become the preferred treatment for patients with advanced non-small cell lung carcinoma (NSCLC) and a programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS) of at least 50%. However, little is known about the value of adding chemotherapy to pembrolizumab in this setting. Therefore, we performed an indirect comparison for pembrolizumab plus chemotherapy versus pembrolizumab, using the frequentist methods. The primary outcomes were overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). Data were retrieved from randomized trials comparing pembrolizumab plus chemotherapy or pembrolizumab monotherapy against chemotherapy. Five trials involving 1289 patients were included. Direct meta-analysis showed that both pembrolizumab plus chemotherapy (ORR: relative risk (RR) 2.16; PFS: hazard ratio (HR) 0.36; OS: HR 0.51) and pembrolizumab alone (ORR: RR 1.33; PFS: HR, 0.65; OS: HR 0.67) improved clinical outcomes compared with chemotherapy. Indirect comparison showed that pembrolizumab plus chemotherapy was superior to pembrolizumab alone, in terms of ORR (RR 1.62, 1.18-2.23) and PFS (HR 0.55, 0.32-0.97). A trend towards improved OS was also observed (HR 0.76, 0.51-1.14). In conclusion, the addition of chemotherapy to pembrolizumab further improves the outcomes of patients with advanced NSCLC and a PD-L1 TPS of at least 50%.

12.
J Bone Joint Surg Am ; 101(7): 613-619, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30946195

RESUMO

BACKGROUND: The search for potential markers for a timely and accurate diagnosis of periprosthetic joint infection (PJI) is ongoing. Previous studies have focused on inflammatory markers and have rarely examined coagulation-related indicators. The purpose of this study was to evaluate the values of plasma fibrinogen, D-dimer, and other blood markers for the diagnosis of PJI through a multicenter retrospective study. METHODS: A total of 565 revision total hip and knee arthroplasty cases were enrolled in this study from January 2016 through December 2017, 126 of which had coagulation-related comorbidities and were analyzed separately. The remaining 439 cases included 76 PJI and 363 non-PJI patients. The definition of PJI was based on the International Consensus Meeting (ICM) on Periprosthetic Infection criteria. The diagnostic values of D-dimer, plasma fibrinogen, the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and white blood-cell (WBC) count were analyzed using receiver operating characteristic (ROC) curves. RESULTS: ROC curves showed that plasma fibrinogen had the highest area under the curve (AUC), 0.852, followed by 2 classical markers, the CRP level and ESR, which had an AUC of 0.810 and 0.808, respectively. D-dimer had an AUC of 0.657, which was the second lowest value and only slightly higher than that of the WBC count, 0.590. The optimal threshold for plasma D-dimer was 1.25 µg/mL, with a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 0.645, 0.650, 0.278, and 0.897, respectively. The optimal threshold for plasma fibrinogen was 4.01 g/L, which showed good sensitivity, specificity, PPV, and NPV, with values of 0.763, 0.862, 0.537, and 0.946, respectively. CONCLUSIONS: Plasma D-dimer may have a very limited diagnostic value for PJI, while plasma fibrinogen, another coagulation-related indicator, exhibits promising performance. Plasma fibrinogen has good sensitivity and specificity for diagnosing PJI, with values similar to those of classical markers, including CRP level and ESR. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

13.
J Bone Joint Surg Am ; 101(6): 531-538, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30893234

RESUMO

BACKGROUND: To our knowledge, no previous studies have compared periprosthetic bone remodeling around monoblock versus modular tapered fluted titanium stems with different stem length and thickness. METHODS: A retrospective comparative study was performed on 139 consecutive total hip arthroplasties (THAs) revised with a tapered fluted modular titanium stem and 114 consecutive THAs revised with a tapered fluted monoblock titanium stem. The latest follow-up radiographs were compared with immediate postoperative radiographs to assess bone restoration in residual osteolytic areas, femoral stress-shielding, spot-welds, and radiolucent lines. Diameter and medullary canal filling of the 2 stems were measured. RESULTS: More patients in the monoblock group demonstrated osseous restoration than in the modular group (p = 0.009), and the modular stem exerted more severe stress-shielding on the femur (p < 0.001). Stem tip spot-welds developed in 88.5% of modular stems compared with 47.4% of the monoblock stems (p < 0.001). Spot-welds developed in 38.8% of modular stems at the modular junction. Partial or circumferential radiolucent lines were observed at the proximal segment of 30.9% of modular stems, compared with 14.0% of monoblock stems (p = 0.002). CONCLUSIONS: Compared with the longer and thinner monoblock stems, modular stems had less proximal osseous restoration in residual osteolytic areas and more severe femoral stress-shielding, stem tip spot-welds, and radiolucent lines around the stems, which were stiffer and had a shorter distal section. The stem diameter and stiffness (which were influenced by stem length, curvature, and modularity) determined bone remodeling patterns. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

14.
Pak J Pharm Sci ; 32(1): 43-51, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30772789

RESUMO

This meta-analysis aimed to confirm the efficacy and safety (side effect) of curcumin for osteoarthritis (OA). Two researchers independently searched the database of Pub Med, EMBASE and Cochrane Library updated to November 2015 to find randomized controlled trials that reported the effect of curcumin on OA. The outcomes of this meta-analysis were Visual analogue scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index scale (WOMAC) and side effect. Furthermore, the quality assessment was performed with Cochrane Collaboration's tool. In addition, standardized mean difference (SMD) and 95% confidence interval (CI) were used for the analysis of continuous data, and the risk ratio (RR) and 95% CI were used to analyze dichotomous data. Sensitivity analysis was performed by using Stata 12.0. A total of 5 studies with 599 patients were included in this study. The results showed that curcumin could significantly improve the WOMAC score (SMD=-0.96; 95% CI:-1.81, -0.10; P=0.03) and VAS score of OA patients (SMD=-1.65; 95% CI:-2.11, -1.19). Furthermore, the side effect rate of curcumin treatment was 0.81times higher than that of ibuprofen treatment. Curcumin can treat OA patients effectively, improving WOMAC score and VAS score, and the side effect of curcumin was not higher than that of ibuprofen.


Assuntos
Antirreumáticos/uso terapêutico , Curcumina/uso terapêutico , Articulações/efeitos dos fármacos , Osteoartrite/tratamento farmacológico , Antirreumáticos/efeitos adversos , Curcumina/efeitos adversos , Avaliação da Deficiência , Humanos , Articulações/fisiopatologia , Osteoartrite/diagnóstico , Osteoartrite/fisiopatologia , Medição da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Resultado do Tratamento
15.
J Immunother Cancer ; 6(1): 155, 2018 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-30577837

RESUMO

BACKGROUND: Immune-checkpoint inhibitors plus chemotherapy are emerging as effective first-line treatment in advanced non-small-cell lung carcinoma (NSCLC), but little is known about the magnitude of benefits and potential clinical predictors. METHODS: We performed a meta-analysis of randomized trials that compared PD-1/PD-L1 inhibitor plus chemotherapy with chemotherapy in first line of treatment for advanced NSCLC. The outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and treatment-related adverse events (AEs). A fixed-effect or random-effects model was adopted depending on between-study heterogeneity. RESULTS: Six trials involving 3144 patients were included. PD-1/PD-L1 inhibitor plus chemotherapy was significantly associated with improvement of PFS (hazards ratio [HR], 0.62; 95% CI 0.57-0.67; P < .001), OS (HR, 0.68; 95% CI 0.53-0.87; P = .002) and ORR (relative ratio [RR], 1.56; 95% CI 1.29-1.89; P < .001), irrespective of PD-L1 expression level. The significant predictor(s) for treatment benefit with combination therapy versus chemotherapy alone were PD-L1 expression level for PFS (P < .001); types of checkpoint inhibitor for ORR (P < .001); histology (P = .025), age (P = .038), gender (P < .001), and types of checkpoint inhibitor (P < .001) for OS. In safety analyses, PD-1/PD-L1 inhibitor plus chemotherapy had significantly higher incidence of adverse events (AEs) of grade 3 or higher (RR, 1.14; P = .007), AEs leading to treatment discontinuation (RR, 1.29; P = .022), serious AEs (RR 1.70; P = .006), immune mediated AEs of any grade (RR, 2.37; P < .001), and immune mediated AEs of grade 3 or higher (RR, 3.71; P < .001). CONCLUSIONS: PD-1/PD-L1 inhibitor plus chemotherapy, compared with chemotherapy, is associated with significantly improved PFS, ORR, and OS in first-line therapy in NSCLC, at the expense of increased treatment-related AEs.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Terapia de Alvo Molecular , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Ensaios Clínicos como Assunto , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Resultado do Tratamento
17.
J Cancer ; 9(19): 3570-3576, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30310514

RESUMO

Background: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for gastric cancer incorporated several new changes. We aimed to assess the comparative prognostic values of the 7th and 8th AJCC pTNM staging systems in patients with gastric cancer (GC), and accordingly, to put forward a refined staging classification. Methods: The SEER database was queried to identify GC patients between 2004 and 2009. GC patients from Sun Yat-sen University Cancer Center (SYSUCC) were used as external validation data. The Kaplan-Meier method and Cox proportional hazards regression models were used to analyze cause-specific survival (CSS). The prognostic performance of different staging schemes was assessed using the concordance index (c-index), Akaike's information criterion (AIC), and likelihood ratio χ2 test. Results: In the SEER cohort, stage migration occurred in 8.74% of patients. Survival analysis showed that it was better to treat T4bN0M0 + T4aN2M0 as stage IIIB and T4bN3bM0 as stage IV. Based on this, we established a new staging system which exhibited a superior c-index (0.7501) to the 7th and 8th AJCC staging systems (0.7498 and 0.7500, respectively). The new staging system also outperformed the 7th and 8th AJCC staging systems in terms of AIC and the likelihood ratio χ2 test. The predictive superiority of the new staging system remained valid in the SYSUCC database. Conclusions: We demonstrated that some stage modifications in the 8th AJCC pathologic staging were unnecessary. Therefore we established a new staging system, which was superior to the 7th and 8th staging systems.

18.
Pain Physician ; 21(5): 483-488, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30282392

RESUMO

BACKGROUND: Total hip arthroplasty (THA) is a well-accepted surgical treatment for terminal hip diseases. OBJECTIVE: To evaluate the effect of preemptive analgesia with parecoxib in patients undergoing primary unilateral THA. STUDY DESIGN: A randomized, double-blind, placebo-controlled study. SETTING: This study was conducted at Peking Union Medical College Hospital and Beijing Jishuitan Hospital in Beijing, China. METHODS: A total of 94 patients scheduled for primary unilateral THA in 2 centers (Peking Union Medical College Hospital and Beijing Jishuitan Hospital) were randomly assigned to receive 40 mg parecoxib (n = 48) or 0.9% normal saline solution (n = 46) 30 minutes before incision. All patients received standardized intravenous patient-controlled analgesia (PCA) postoperatively. Preoperative baseline data, surgery-related conditions, postoperative Visual Analog Scale (VAS) pain score, cumulative narcotic consumption of PCA, and complications were compared between the parecoxib group and the placebo group. RESULTS: There were no significant differences in postoperative VAS pain score, cumulative narcotic consumption of PCA, proportion of analgesic remedy, and complications between the 2 groups. LIMITATIONS: Only a single dose of parecoxib was used without including a dose-dependent control group. CONCLUSION: A single dose of parecoxib 30 minutes before incision did not provide effective preemptive analgesia for the management of postoperative pain after primary unilateral THA. The possible effect of preemptive analgesia with parecoxib needs further investigation. KEY WORDS: Total hip arthroplasty, pain, parecoxib, COX-2 selective inhibitor, preemptive analgesia, clinical trial, patient-controlled analgesia, analgesics.

19.
Photodiagnosis Photodyn Ther ; 24: 182-184, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30290230

RESUMO

A case of recalcitrant dissecting cellulitis of the scalp (DCS) in a 23-year-old male patient was treated with 4 times of topical ALA-PDT at intervals of 10-15 days. The patient responded well without any unbearable adverse effects and presented satisfactory effects. Before applying this therapy, the patient and his doctors had tried other methods, specifically glucocorticoids, intradermal injection, and even surgical treatment, but none of them had presented satisfactory effects. This suggests that topical ALA-PDT could be an effective and safe alternative for DCS patients who are refractory to other standard therapies.

20.
J Arthroplasty ; 33(12): 3724-3733, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30243881

RESUMO

BACKGROUND: Reconstructing the normal hip biomechanics is important for a successful revision total hip arthroplasty (THA). Little is known about whether using metal augments in revision THA is biomechanically superior to traditional techniques. METHODS: A retrospective review was conducted on 74 consecutive THAs revised using metal augments with a cementless hemispherical cup and 77 consecutive THAs revised using the jumbo cup, all with a minimum 2-year follow-up. Biomechanical parameters were measured before and immediately after the revision. Radiological and clinical outcomes at follow-ups were also evaluated. RESULTS: The metal augment group had a reconstructed center of rotation (COR) that was 6.5 mm closer to the anatomic COR in height (P < .001), had 3.6 m smaller cup size (P < .001), and had 5.7 mm less head-cup difference (P < .001). Moreover, there was a reconstructed COR that was much closer to the anatomic COR (vertical distance: 1.8 vs 14.1 mm, P < .001; horizontal distance: -2.1 vs 7.9 mm, P = .013), had 4.1 mm greater femoral offset (P = .006), and had 8 mm less leg length discrepancy (P = .035) in the subgroup of Paprosky type III bone defects when compared to the jumbo cup group. All cup-augment constructs were radiologically stable with a higher mean postoperative Harris Hip Score (P = .012). One jumbo cup was radiologically unstable. CONCLUSION: In revision THA, utilizing metal augments helps to restore the COR position more precisely, avoid using a larger cup, reduce head-cup difference, rebuild femoral offset, and decrease leg length discrepancy, particularly with Paprosky type III bone defects. Moreover, it provides satisfactory radiological and clinical outcomes in the short term.

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