泌尿肿瘤免疫检查点抑制剂相关性肌炎的临床特征

目的: 分析泌尿肿瘤免疫检查点抑制剂(immune checkpoint inhibitor, ICI)相关性肌炎的临床特征及治疗转归。方法: 选择2018年3月—2022年3月北京大学第一医院泌尿外科诊治的8例泌尿肿瘤ICI治疗后免疫相关性肌炎患者的临床资料进行回顾性分析，对人口学特征、用药方案、临床症状、实验室指标、肌电图检查、病理表现、治疗转归等信息进行分析。结果: 8例患者包含女性2例、男性6例，中位年龄68岁，均因泌尿肿瘤接受ICI治疗，包括2例上尿路尿路上皮癌(upper tract urothelial carcinoma，UTUC)、3例肾细胞癌(renal cell carcinoma，RCC)和3例膀胱癌(bladder cancer, BCa)。首次ICI治疗至发现免疫相关性肌炎的中位时间为39.5 d，中位疗程为2个疗程。主要症状为肌肉酸痛乏力，5例伴眼睑下垂，3例继发横纹肌溶解，5例合并心肌炎，1例合并重症肌无力，1例合并肠炎。发现合并免疫相关性心肌炎的患者首次接受ICI治疗至肌炎起病的间隔时间更短(P=0.042)。8例患者均有转氨酶及肌酶谱指标显著升高，5例患者出现自身抗体阳性。3例患者完善了肌肉活检，表现出典型的骨骼肌炎性肌病样病理改变，伴CD3⁺、CD4⁺、CD8⁺、CD20⁺淋巴细胞和CD68⁺巨噬细胞浸润。诊断免疫相关性肌炎后8例患者均立即停用ICI治疗，使用甲泼尼龙单独或合并丙种球蛋白静脉注射后病情均好转。结论: ICI治疗后免疫相关性肌炎是具有独特临床及病理特征的免疫相关不良反应(immune-related adverse events, irAEs)，常见合并心血管不良反应，立即停用ICI并开始糖皮质激素治疗可以及时改善患者病情。     

Multifocal heterotopic ossification in a man with germline variants of LIM Mineralization Protein-1 (LMP-1)

A 54-year-old man with a history of unimelic, post-traumatic multifocal heterotopic ossification (HO) and normal genetic analysis of ACVR1 and GNAS had variants of unknown significance (VUS) in PDLIM-7 (PDZ and LIM Domain Protein 7), the gene encoding LMP-1 (LIM Mineralization Protein-1), an intracellular protein involved in the bone morphogenetic protein (BMP) pathway signaling and ossification. In order to determine if the LMP-1 variants were plausibly responsible for the phenotype observed, a series of in vitro experiments were conducted. C2C12 cells were co-transfected with a BMP-responsive reporter as well as the LMP-1 wildtype (wt) construct or the LMP-1^T161I or the LMP-1^D181G constructs (herein designated as LMP-161 or LMP-181) corresponding to the coding variants detected in the patient. A significantly increased BMP-reporter activity was observed in LMP-161 or LMP-181 transfected cells compared to the wt cells. The LMP-181 variant exhibited BMP-reporter activity with a four-fold increase over the LMP-1 wt protein. Similarly, mouse pre-osteoblastic MC3T3 cells transfected with the patient's LMP-1 variants expressed higher levels of osteoblast markers both at mRNA and protein levels and preferentially mineralized when stimulated with recombinant BMP-2 compared to control cells. Presently, there are no pathogenic variants of LMP-1 known to induce HO in humans. Our findings suggest that the germline variants in LMP-1 detected in our patient are plausibly related to his multifocal HO (LMP1-related multifocal HO). Further observations will be required to firmly establish this gene–disease relationship.     

Facial myonecrosis following COVID-19

Myositis and myonecrosis are rare sequela of coronavirus disease 2019 (COVID-19). Until now, it has not been seen in muscles of the head and neck. We present a 22-year-old male with 4 months of retroauricular headaches following COVID-19 infection. Magnetic resonance imaging revealed rim-enhancing fluid collections in the bilateral masticator spaces which were sampled by fine-needle aspiration. We also discuss this case in the context of the current understanding of COVID-19-related myositis.     

Radiología de las tumoraciones palpables en el paciente pediátrico. Parte 2

Palpable tumors in children are a common reason for consulting a radiologist. The origin of these lesions varies widely, and although they are common, classic radiology books do not cover some of them.This series of two articles aims to review the clinical and radiological characteristics of a selection of palpable tumors in children that radiologists need to be familiar with.