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Clin Cancer Res ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526363


PURPOSE: Targeted therapy and immunotherapy are transforming the treatment approach for intrahepatic cholangiocarcinoma (ICC). However, little is known about the intertumor heterogeneity (ITH) of multifocal ICC and its impacts on patient response to these treatments. We aimed to characterize the immunogenomic and epigenomic heterogeneity of multifocal ICC to guide treatment decision making. EXPERIMENTAL DESIGN: We obtained 66 tumor samples from 16 patients with multifocal ICC and characterized the tumor and immune heterogeneity using whole-exome sequencing, bulk and single-cell RNA sequencing, methylation microarray, and multiplex immunostaining. Patients were divided into high- or low-ITH groups according to the median ITH index. Two independent cohorts were used to validate findings. Responses to anti-PD-1 therapy were assessed. RESULTS: Multifocal ICC presented considerable intertumor genomic, transcriptional, and epigenomic heterogeneity within a patient in high ITH group. The immune profile among multiple tumors within a patient was relatively less heterogeneous in high- or low-ITH group, and consistent responses of multiple tumors to anti-PD-1 immunotherapy were observed. Unsupervised clustering of immune markers identified one low and one high immune subtype, with higher immune cell infiltration, closer tumor-immune cell interactions, and upregulated IFN-signature expression in high-immune subtype. Determining expression levels of CD8B and ICOS facilitated this immune classification and prediction of patient prognosis. Finally, promoter DNA methylation contributed to different immune profiles of two subtypes by regulating immune-gene expression. CONCLUSIONS: There is comprehensive heterogeneity in the genome, transcriptome, and epigenome of multifocal ICC. On the basis of the less heterogeneous immune profile of ICC, we suggest an immune classification that stratifies patients' prognosis and may support personalized immunotherapy.

Hemodial Int ; 25(4): 465-472, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34133063


INTRODUCTION: The use of Acuseal arteriovenous graft (AAVG) is spreading in end-stage renal disease (ESRD) patients for its advantages in early cannulation. However, comparison of clinical outcomes between AAVGs and standard arteriovenous grafts (SAVGs) is limited. In this study, we compared the performance of AAVGs and SAVGs. METHODS: Consecutive ESRD patients underwent prosthetic vascular access between October 2017 and May 2019 at a single center were identified. Patients were divided into AAVG group and SAVG group. Patients' demographics, perioperative characteristics, and clinical outcomes were collected. Primary, primary assisted, and secondary patency rates were compared using Kaplan-Meier analyses. Postsurgery complications were compared using chi-square test or the Fisher's exact test. FINDINGS: A total of 304 arteriovenous grafts (AVGs) were implanted in 145 males and 159 females (mean age, 60.1 years; range, 20-91 years), comprising 143 AAVGs and 161 SAVGs. Median time to first cannulation was 3 days (interquartile range [IQR], 1-15 days) in the AAVG group and 30 days (IQR, 20-52 days) in the SAVG group (P < 0.001). Adjusted primary, primary assisted, and secondary patency at 12 months were not significant different between AAVGs and SAVGs (P = 0.911, P = 0.945, and P = 0.640, respectively). There was no statistical significance in regards to thrombosis (AAVG, 34.3%; SAVG, 26.1%; P = 0.120) and infection (AAVG, 4.9%; SAVG, 2.5%; P = 0.261) between the groups. DISCUSSION: Acuseal grafts provide comparable patency, and complication rates to SAVGs, with less time to first cannulation from the graft implanted.

Biomed Pharmacother ; 131: 110767, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33152929


Increasing evidence suggests that an exogenous electromagnetic field might be involved in many biologic processes which are of great importance for therapeutic interventions. Pulsed electromagnetic fields (PEMFs) are known to be a noninvasive, safe and effective therapy agent without apparent side effects. Numerous studies have shown that PEMFs possess the potential to become a stand-alone or adjunctive treatment modality for treating musculoskeletal disorders. However, several issues remain unresolved. Prior to their widely clinical application, further researches from well-designed, high-quality studies are still required to standardize the treatment parameters and derive the optimal protocol for health-care decision making. In this review, we aim to provide current evidence on the mechanism of action, clinical applications, and controversies of PEMFs in musculoskeletal disorders.

Campos Eletromagnéticos , Terapia de Campo Magnético/métodos , Doenças Musculoesqueléticas/terapia , Animais , Ensaios Clínicos como Assunto/métodos , Tomada de Decisões , Humanos , Projetos de Pesquisa
Photodiagnosis Photodyn Ther ; 31: 101918, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32663613


Condyloma acuminatum is a sexually transmitted disease caused by human papillomavirus infection, which mostly occurs in the external genitalia, vulva, perianal, and the Intraurethral condyloma acuminatum is relatively rare. Treatment of urethral warts present a challenge especially if the proximal urethra is involved. Here, we report a case of intractable urethral condyloma acuminatum involving the urethral meatus and mid penile urethra with scar. This case suggested that local Photodynamic therapy in condyloma of the whole anterior urethra appears to be not only safe and effective, but also might be able to improve existing scars.

Condiloma Acuminado , Fotoquimioterapia , Condiloma Acuminado/tratamento farmacológico , Feminino , Humanos , Masculino , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Triazenos , Uretra
Cancer Manag Res ; 11: 10665-10673, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31920376


Background: The reverse shoulder arthroplasty (RSA) may be a promising alternative for proximal humerus tumours because of good postoperative shoulder function. However, the conventional reverse shoulder prosthesis can not meet individual needs and RSA has been associated with a relatively high complication rate. Therefore, implant design and surgical reconstruction technique warrant further study. Methods: Between September 2015 and May 2018, 7 patients were treated via RSA after en-bloc resection of the proximal humerus tumours. A 3D-printed guiding baseplate was used to assist the implant of the 3D-printed glenoid prosthesis; a personalized humerus prosthesis was used to reconstruct the proximal humerus. The functional outcomes were assessed by range of motion (ROM) of the shoulder joint, Musculoskeletal Tumour Society (MSTS) functional score, and Toronto Extremity Salvage Score (TESS). We also analyzed tumour recurrence, metastases, and complications associated with the reconstruction procedure. Results: All patients were observed for 14 to 36 months, with an average of 23.6 months. At the final follow-up, the mean MSTS score was 85.7% (range, 73.3-93.3%), and the mean TESS score was 90.0% (range, 84.1-95.9%). No instability, infection, scapular notching, loosening or fracture were observed in this series. One patient with GCT suffered from pulmonary metastasis, while one with osteosarcoma died because of pulmonary metastasis. Conclusion: The 3D-printed guiding baseplate facilitated the accurate implantation of the glenoid prosthesis. The RSA based on a 3D-printed glenoid prosthesis and a personalized custom-made humerus prosthesis significantly improved the shoulder function and decreased the complication rate. Further studies of a larger scale with longer follow-up are required to validate this technology.