简介:

深圳市宝安区人民医院（深圳大学第二附属医院、深圳市第八人民医院）始建于1984年，2011年评定为综合性“三级甲等”医院，是深圳市西部急救、医疗、康复、教学、科研和公共卫生的重要基地，先后荣获“全国百佳医院”、“国家级青年文明号”、“全国卫生系统先进集体”、“全国卫生文化建设先进单位”、“全国卫生系统行风建设先进集体”、“全国卫生系统思想政治工作先进单位”等殊荣。医院占地面积5.3万平方米，总建筑面积14万平方米，编制床位1250张，实际开放床位1097张。医院二期改扩建项目总投资60亿元，建筑面积66万平方米，规划床位3300张，将于2024年开始逐步交付使用。医院现有职工2348人，其中高级职称505人，博士生导师10人，硕士生导师36人，博士研究生90人，硕士研究生418人。深圳市地方级领军人才1人，海外高层次人才C类4人，深圳市后备人才7人。在全国学术团体中，有国家级学会专业组主任委员及副主任委员共7名，省级学会主任委员及副主任委员共21名，深圳市级学会主任委员及副主任委员55名。医院设有46个临床学科，15个医技科室，19个社区健康服务中心，形成完备的内、外、妇产、儿、五官、医技等的三级医院学科体系。医院创建了省级重点学科2个（急诊医学科、临床护理）、深圳市医学重点学科1个（急诊医学科），区重点学科9个（急诊医学科、创伤骨科、肾病科、康复医学科、内分泌科、泌尿外科、重症医学科、普通外科、脊柱外科）。目前医院已建成5大急救中心（胸痛中心、创伤中心、卒中中心、重症孕产妇救治中心、危重儿童及危重新生儿救治中心），其中胸痛中心和卒中中心分别获得中国胸痛中心和中国卒中中心认证。在2020—2021年中国医院科技量值排行榜中，我院急诊科排名均为100名以内，是唯一进入全国百强的县区级医院急诊医学科。医院先后引进解放军总医院付小兵院士创伤团队、福建中医药大学陈立典教授康复团队、北京协和医院于学忠教授急诊医学团队、广东省心血管病研究所陈纪言教授团队、澳大利亚昆士兰大学脑研究院团队等五个高水平“三名工程”学术团队。依托医学“三名工程”和高层次医学团队，医院不断开展新技术、新项目，大病重病救治能力持续提升。腹腔镜全膀胱切除术/肾盂癌根治术/前列腺癌根治术、显微镜联合计算机导航上颈椎畸形减压复位固定融合术、巨大肝癌极限肝切除术、复杂下肢畸形微创矫形术/胫骨横向骨搬移（TTT）技术、高位动静脉内瘘翻转术/人造血管动静脉内瘘成形术、ERCP胆道取石术/经口食道括约肌切除术等，在区域内处于领先水平；颅内动脉狭窄支架成形术、颅内动脉狭窄球囊扩张术等达到省市领先水平。现有固定资产10.32亿元，其中设备资产8.47亿元，拥有原值大于1万元医疗设备3226台/套，100万以上设备183台，1000万以上设备6台。医院拥有西门子3.0TMRI2台，64排螺旋CT2台，DSA2台，高档四维彩超仪多台，可实现术中CT导航的O型臂系统1套，骨科3D打印设备1台，可用于神经外科及骨科手术的手术导航系统1套，全自动生化流水线等大型先进医疗设备。医院坚持医教研协同发展，1998年被评定为广东省高等医学院校教学医院，2015年建立深圳市博士后创新实践基地，2016年经评审成为广东医科大学宝安临床医学院、广东省住院医师规范化培训协同单位，2018年挂牌深圳大学第二附属医院。在教学管理上，形成“教学管理委员会－科教科－教研室（组）”三级管理体系，院长任主任委员；成立了内科、外科、妇产、儿科、急诊、全科、口腔、麻醉共8个教研室、35个临床教学组。2019—2022年，共接收“3+2”模式临床医学专业理论授课及随堂见习小班化教学236人、“2+2”模式护理专业191人；接收医疗实习生1195人、护理实习生522人；累计招收全科医师34人；累计招收硕士研究生89名，全日制博士研究生1名，其中66名研究生完成毕业论文答辩并顺利毕业；先后培养博士后5名。近5年医院获批科研立项共317项，其中国家自然科学基金6项，省部级课题8项，市厅级课题39项，区局级264项；累计发表论文1012篇，其中SCI论文151篇，北大中文核心期刊121篇，中国科技论文统计源期刊182篇；累计出版专著45部；累计获得授权专利46项。2019年“骨与关节多组织损伤创新型模型构建及分子治疗的基础研究”荣获深圳市科学技术奖自然科学奖二等奖。医院在打造基层区域医疗中心和医疗集团化建设过程中，不断创新“两融合一协同”的服务模式，搭建起以宝安区人民医院互联网医院为平台、九大“智慧医学服务中心”为支撑的5G互联网智慧医疗服务体系，在不断探索“AI+5G+云”等新一代技术深度融入医疗服务过程中，平台逐步实现“医疗集团上下（1家区域三甲综合医院+1家街道三级医院+1家分院+32家社区健康服务中心）”和“医共体内外（三甲医院+对口帮扶县人民医院+区域合作医疗机构+合作企业门诊部）”的处方评审、病理诊断、心电诊断、超声诊断、影像诊断、检验危急值管理等远程医疗服务的高度同质化、精准化和高效化，打造出“一点触网，全网协同”的智慧医疗服务“宝安样板间”。医院十分重视党建工作，实行党委领导下的院长负责制，健全组织领导体系，优化党支部设置，目前有党员706名，下设17个党支部，落实“把支部建在科室上”。院党委2020年获评“深圳市先进基层党组织”、“深圳市抗击新冠肺炎疫情先进集体”、深圳市委卫生工委“2019—2020年度先进基层党组织”荣誉等。2019年创新开展“党员志愿者到人民中去”活动，获评健康报2019年“寻找卫生健康基层党建创新案例”活动“创新案例奖”、2020年深圳市现代医院管理创新项目“簕杜鹃”奖、“2019年度宝安区党建创新示范项目”等，该项目被宝安区委写进2021年度党建工作报告。风雨荣光四十载，继往开来谱新篇。宝医人将秉承“厚德、敬业、精医、卓越”的院训，坚持“生命至上，医术至精，服务至诚”的办院理念，扬帆起航，为将宝安区人民医院建设成为高水平三级甲等综合医院而不懈奋斗。男性乳腺纤维囊性增生的原因和内分泌失调以及精神因素直接相关，内分泌失调以及精神因素，乳房，口服药物或者是手术的方法来处理，乳腺癌，忌口油脂类食物,忌食生冷和辛辣等刺激性的食物。，一般临床的望、触即可做出诊断，。

true 许向前主任医师

三级甲等深圳市宝安区人民医院

好评率：- 接诊量：- 平均响应：-

脱发、痤疮（痘痘）、湿疹，皮炎，荨麻疹，性传播疾病等

true 孔庆元副主任医师

三级甲等深圳市宝安区人民医院

好评率：- 接诊量：- 平均响应：-

肝脏、胆囊、胆管、胰腺、胃、小肠、结直肠、腹外疝等常见病、危重症、疑难杂症的诊断与治疗。尤其擅长胃癌、结肠癌、直肠癌、胃肠间质瘤以及各种腹外疝（腹股沟疝、股疝、脐疝、切口疝、白线疝等）的微创手术及胃肠道恶性肿瘤的综合治疗。熟练掌握各种腹腔镜手术及消化内镜的诊疗。

false 王霞副主任医师

三级甲等深圳市宝安区人民医院

好评率：- 接诊量：- 平均响应：-

婚恋关系咨询、个人成长咨询、亲子关系咨询及各种类神经症、抑郁症等的心理咨询和治疗。

false 邱立副主任医师

三级甲等深圳市宝安区人民医院

好评率：- 接诊量：- 平均响应：-

临床病理诊断，特别是女性生殖系统，淋巴造血系统

true 张泉水主任医师

三级甲等深圳市宝安区人民医院

好评率：- 接诊量：- 平均响应：-

心理咨询，睡眠

true 卢震辉主任医师

三级其他深圳市前海蛇口自贸区医院

好评率：99% 接诊量：1791 平均响应：-

肝癌、胆管癌、胆管结石、胆囊结石、胰腺疾病等

true 黄呈辉主任医师

三级甲等深圳市宝安区人民医院

好评率：95% 接诊量：24 平均响应：2小时

主要从事肝病和感染病临床工作，擅长乙肝、丙肝、肝硬化、脂肪肝、自身免疫肝病和疑难肝病等诊治

true 柳晖主任医师

三级甲等深圳市宝安区人民医院

好评率：100% 接诊量：9 平均响应：-

重睑术，眼袋切除，瘢痕综合治疗，微整形，脂肪注射，烧伤重症救治，慢性创面修复。

true 刘尚典副主任医师

三级甲等深圳市宝安区人民医院

好评率：100% 接诊量：54 平均响应：-

冠心病，心脏瓣膜病，先天性心脏病，主动脉疾病的外科诊治；微创心外科。参与心脏置换5例。对重症心脏病患者，心脏终末期患者的治疗有自己独到的见解。

true 杨梅主治医师

三级甲等深圳市宝安区人民医院

好评率：99% 接诊量：5864 平均响应：15分钟

新型冠状病毒肺炎，社区获得性肺炎，高血压，糖尿病，冠心病，痛风，幽门螺旋杆菌感染，慢性胃炎，肝病

接诊医生：

2024-10-31 13:31:20

科普文章

男人要长点心，这种病不是女人的专利，男人也会出现

乳腺增生是一种比较常见的疾病，但是在人们传统的认知当中，乳腺增生早已被打上女性的“专利”，很多人都认为乳腺增生是只有女性才会患有的病症。但事实上，乳腺增生这种问题不论男性还是女性，都有罹患的可能性，只是女性患者多一点而男性患者少一点罢了。

男性患乳腺增生的原因

乳腺的正常发育，无论是男性还是女性，都是通过人体内的雌激素、孕酮、生长激素、催乳激素等激素的作用和平衡来实现的。雌激素是主要存在于女性体内的重要激素，但在男性的体内，除了雄性激素外，也有由睾丸和肾上腺皮质分泌的少量的雌激素。正常情况下，男性的乳房会因其体内占主导地位的雄激素的制约而处于不发育状态的，但当其体内的雌激素分泌过多或者出现排泄障碍时，就会导致男性体内的激素水平失衡，从而导致男性的乳腺因受到刺激而出现组织增生。经相关的研究表明，男性乳腺发育最主要的原因就是其体内雌激素的量增多。

男性乳腺增生的症状与分类

男性出现乳腺增生时，其单侧或双侧可触及的乳腺组织一般会呈现圆盘状结节或者弥漫性增大，有时还可能会伴有乳头和乳晕的增大；另外，患有乳腺则生的男性，其乳房的局部通常还有隐痛不是或者触痛感，少数患者在挤压乳头时甚至还可能会有少量白色的分泌物溢出。

男性乳腺增生的危害及预防

男性患乳腺增生的几率虽然要原低于女性，但一旦男性患上此疾病，不但会在身体上可能会导致男性不育，出现癌变的可能性也比女性要大。男性患有乳腺增生后，也会给患者带来巨大的心理压力。所以，预防乳腺增生对于男同志来说同样重要。在预防乳腺增生方面，男性需要做的与女性基本相同，如平日里应该保持乐观的心态及平稳的情绪，要知道不良的心理因素，如过度紧张、刺激忧虑、悲伤等情绪容易造成神经衰弱，从而会加速内分泌失调，以促使乳腺增生的加重；另外，养成良好的饮食、睡眠、运动等生活习惯，不但对于保持健康的体重、提升体质意义重大，最重要的是可以有助于保持体内的内分泌平衡，进而利于男性乳腺增生的预防。

男性乳腺增生各期的表现

在临床上，大部分患者认为只有女性患者才有乳腺增生症，实际上男性朋友也有可能会患有乳腺疾病，并且乳腺增生的各个期的症状表现也是不一样的，具体男性乳腺增生个期的症状表现大致有以下几个方面。

第一，乳腺小叶增生期，这也是初期的一个表现，男性患者乳腺增生初期，一般起病年龄都是比较年轻的，大约在20岁到30岁之间，只是轻微的增生，症状不是很明显，往往不受到重视，大部分患者不会选择治疗，任由其发展，这种情况可能会继续的进展，发展到下一期。

第二，乳腺腺病，也就是乳腺增生的第二期，这时多伴有乳腺导管扩张，是由乳腺小叶增生期演变而来的，发病年龄稍晚一些，大约在30到40岁左右的人群当中，症状表现也是比较明显的并且比较严重，会见到明显增大的乳房，有的会伴有疼痛感、刺痛感、胀痛感，这时需要引起我们的重视，往往治疗也是比较困难的，久不治愈对男性心理有一定的影响，甚至会出现内分泌紊乱、精神抑郁等等。

第三，囊性增生期，这也是在第二期进一步加重的情况下发展而来的，年龄也是更往后一些，大约在男性患者40到55岁之间，这时患者会出现乳腺导管扩张合并上皮细胞增生，这时需要注意防止癌变，因为囊性增生期恶变率可达到70%以上，必须积极的进行治疗，切勿耽误病情引起严重的后果。

乳腺增生：正常的生理现象

在临床中提到的乳腺增生，多是良性的。比如青春期女孩子乳房发育长大；比如妊娠哺乳期间乳房发育长大、为新生儿做准备；比如乳房随着月经周期而发生的周期性乳房疼痛，这些都属于正常乳腺发育与退化中失常范畴，这样的乳腺增生不是病，通常无需用药和治疗。

提醒大家，乳腺增生的好与坏，不是根据疼痛的程度区分，大多“坏的”东西不一定痛。有增生、有包块及时找医生排查，确认良性就不必担心了。

凭胸而论，这7个乳房问题，女性也一定不知道

乳房一直是「性感」的代言，男性为之痴狂，女性为之迷茫。

根据《中国乳腺疾病调查报告》显示：我国城市乳腺癌的死亡率增长了38.1% 。在无症状女性人群中，各种乳腺疾病患者竟达到 52.4%。

美好的胸型是女人自信的源泉，但是很多疑问也同时存在。

我们整理了7大问题，一起来看看吧。

问题1：乳房是个器官吗？

答：当然是。

器官都是在人体的构成里起到一定的作用，乳房的作用就是分泌乳汁。

乳汁产生于乳腺小叶，之后沿着乳房内的小导管到达乳头开口分泌出来。那男性为什么不能泌乳呢？因为他们的乳房内没有乳房小叶呀。

问题2：两边乳房一样大吗？

答：两边一样几乎是不可能的。

日本人曾在成熟女性上涂抹石膏，然后在石膏里面盛水来计算乳房的大小，结果发现每个女人的乳房两边都不是一样大小。

但是，如果两侧乳房大小差异很大，可能要怀疑一种罕见的疾病——波兰综合征。男性患者大多数表现为两边胸部不对称；而女性患者胸壁的畸形就会使双侧乳房的大小不一样。

主要原因是患病一侧锁骨下的血液供给有问题，导致这侧上肢和胸壁发育不良而出现畸形。如出现这种情况，请尽快就医。

问题3：内衣都买合适了吗？

答：超过7成女性觉得内衣不合适。

内衣尺寸小了，穿着相当难受，肩勒的疼不说，背上还勒出一道道的赘肉。尺寸大了，内衣老滑动，或者被人一戳就空了...

内衣尺寸不对可能会导致内衣对乳房的支撑不足，从而引发一系列的毛病，包括不良体态、脖子和背部疼痛，甚至影响手部和肩部的神经。

女性的胸部在不同时期，尺寸变化可以很大，比如在减肥前后、绝经前后和生产前后；而且不仅是大小，女性胸部的紧实度也会发生变化。

所以，不同时期要买有不同支撑力的内衣，不能一直穿着少女款，而且买之前，一定要试穿。

问题4：乳腺增生会癌变吗？

答：一般不会，但…

乳腺增生是指乳腺的良性疾病，表现为周期性的乳房疼痛与增生性肿块。

部分乳腺增生症患者可以出现乳腺增生结节，结节本身发生癌变的机会并不大，但是乳腺的恶性结节经常与乳腺增生结节同时存在。

所以，乳腺增生伴有结节时，需要每3-6个月左右进行乳腺彩超检查1次，以及时了解病情的变化。

问题5：男性乳房也发育吗？

答：会，分生理性和病理性的。

男性乳腺发育症现在是越来越多了。很多男性只是觉得「就是胖的」，但还有很多疾病要引起重视。

男性乳腺发育可以和其他诸多疾病同时并存，比如睾丸功能低下、先天性性腺发育不足、甲亢、肝硬化、恶性肿瘤、睾丸肿瘤等。

外源性的雌激素也可以引起，因此在日常生活中要注意避免含有激素的饮料、食物等。长期口服一些药物西咪替丁、螺内酯、洋地黄、抗精神药等可以引起雌激素增高。

问题6：喝豆浆能丰胸吗？

答：当然不能。

女性的乳房发育主要是靠雌激素的作用。而豆浆中的植物雌激素，也就是大豆异黄酮，只是结构上比较类似雌激素。

当体内植物雌激素含量很高时，它与受体的结合妨碍了生理雌激素与受体的正常结合，反而起到了抑制性效果，相当于降低雌激素水平、削弱雌激素作用，也就是说会「适得其反」。

所以，豆浆不会有任何丰胸的作用。

问题7：副乳危险吗？需要就医吗？

答：看情况。

很多人的腋下其实都有些「肉」，但未必是副乳。

因为副乳有真性副乳和假性副乳之分，假性副乳里只有脂肪，并没有得癌危险；它的手感摸上去像嘴唇一样是柔软，但是乳腺摸上去像鼻子的触感，是有韧性的。

您不妨按照我们的方法自己检查一下！但如模棱两可无法判断，您可以到医院做B超检查，能准确判断是乳腺还是脂肪哦~

参考文献：

[1] 《中国抗癌协会乳腺癌诊治指南与规范》（2017版）

审稿医生 | 洛阳市妇女儿童医疗保健中心乳腺外科侯毅

责任编辑 | 黑凤梨

乳腺囊性增生病的检查有哪些？

一、实验室检查:

总物细针吸取细胞学检查乳腺囊性增生病肿物多呈两侧性、多肿块性,肿块病变的发展情况不一,采取多点细针吸取细胞学检查常能全面反应各肿快的病变情况或性质,特别能为大多的病例提供早期诊断意见。

二、乳头溢液细胞学检查:

少数患者有乳头溢液肉眼所见多为浆液性、浆液血性,涂片镜检可见导管上皮泡沫细胞、红细胞、少许炎症细胞及脂肪蛋白质等无形物。

三、辅助检查包括:

1. 钼靶 x 射线,在过去我们钼靶 x 射线比较常用,它能很清楚的显示病变部位呈现棉花团或毛玻璃状边缘模糊不清的高密度增高影,可见不规则增强阴影中有圆形透亮阴影。乳腺囊性增生病肿块需与乳腺癌的肿块进行鉴别:前者无血运增加,皮肤增厚和毛刺等恶性征象,若有钙化也多散在,不像乳腺癌那样密集。

2. B 超检查, B 超诊断技术发展很快诊断率也不断提高,对本病检查时常显示增生部位成不均匀低回声和无肿块的回声囊肿区。

3. 磁共振成像检查,典型的磁共振成像表现为乳腺导管扩张,形态不规则,边界不清楚,扩张导管的信号强度在 1 加全相上低于正常腺体组织,病变局限于某一区也可弥漫于分布整个区域或在整个乳腺,本病的 MRI 通常呈对称性改变。

案件31-2023：一名79岁男性，身体不自主运动、一过性反应迟钝

以下内容来源于新英格兰医学杂志。

Presentation of Case

Dr. Carrie Chui (Neurology): A 79-year-old man was admitted to this hospital because of involuntary movements on the left side and transient unresponsiveness.

The patient had been in his usual state of health until 9 months before admission, when involuntary movements of the left shoulder and left side of the face developed. The movements were described by the patient as twitching, were not associated with a change in the level of consciousness, and resolved after 1 to 2 minutes. During the next 6 months, the patient had similar episodes approximately once per month, but the episodes increased in duration, lasting 5 to 6 minutes.

Three months before admission, the episodes of involuntary movements increased in frequency, and the patient was evaluated by his primary care physician. The physical examination was normal. Results of kidney-function tests were normal, as were blood levels of glucose and electrolytes, except for the sodium level, which was 129 mmol per liter (reference range, 135 to 145). There was a history of inappropriate antidiuretic hormone secretion, and the sodium level was similar to levels obtained during the past 4 years. Magnetic resonance imaging (MRI) of the head (Figure 1A), performed before and after the administration of intravenous contrast material, revealed a focus of enhancement in the right middle frontal gyrus that was thought to be a small vascular anomaly. Electroencephalography (EEG), performed with the patient in awake and drowsy states, revealed rare, brief, focal slowing in the left temporal lobe during drowsiness; no epileptiform abnormalities were present.

Figure 1

MRI of the Head and CT Angiogram of the Head and Neck.

Two months before admission, the patient was evaluated in the epilepsy clinic affiliated with this hospital. He reported that the episodes of involuntary movements had increased in both frequency and duration, occurring once or twice per day and lasting approximately 10 minutes. Episodes began with tingling and numbness in the left leg that prompted the patient to voluntarily stomp the left foot to relieve the uncomfortable sensation. Then, the patient had involuntary movements that he described as an uncontrollable invisible force moving the left leg and arm, with hyperextension of the arm backward and pronation of the wrist. There was associated numbness in the distal portions of the left third, fourth, and fifth fingers and involuntary movement of the left cheek. No prodromal symptoms occurred. The patient had awareness during the episodes, and after the episodes, he felt fatigued but had a normal level of consciousness, without confusion. The examination in the epilepsy clinic was normal. A diagnosis of seizure disorder was considered, and treatment with levetiracetam was started.

Three weeks before admission, the patient was again evaluated in the epilepsy clinic. He reported that the episodes of involuntary movements still occurred on a daily basis but had decreased in duration and involved only the left leg, without abnormal movements of the arm or face. Dizziness, headache, and weakness had developed and were attributed to the use of levetiracetam. The patient’s family had recorded a video of one of the episodes of involuntary movements. After reviewing the video, the patient’s neurologist thought that the episodes were less likely to be caused by seizures and more consistent with choreoathetoid movements. Cross-tapering of medications — with the simultaneous administration of levetiracetam in decreasing doses and clobazam in increasing doses — was initiated, and the patient was referred to the movement disorders clinic affiliated with this hospital.

On the morning of admission, an episode of involuntary movements of the left leg and left shoulder occurred and persisted for 1 hour. Several hours after the symptoms abated, the patient’s wife found the patient to be unresponsive; he was sitting in a chair. Emergency medical services were called, and when they arrived, the patient was responsive. The fingerstick blood glucose level was 180 mg per deciliter (10.0 mmol per liter) and the blood pressure 110/80 mm Hg. The patient was transported to the emergency department of this hospital for further evaluation.

In the emergency department, the patient reported dysuria and increased urinary frequency. The patient’s daughter noted that he had been more anxious during the past 3 years and occasionally had trouble with memory. Other medical history included Barrett’s esophagus, benign prostatic hypertrophy, chronic hepatitis B virus infection, eczema, gastroesophageal reflux disease, hypertension, nonischemic cardiomyopathy, and osteoporosis. There was no history of head trauma or extended loss of consciousness. Medications included aspirin, atorvastatin, doxazosin, finasteride, omeprazole, metoprolol, sacubitril, and valsartan. There were no known drug allergies. The patient was a lifelong nonsmoker and drank alcohol rarely; he did not use illicit drugs. His mother had had gastric cancer, and his sister had had esophageal cancer; there was no family history of seizures.

On examination, the temporal temperature was 36.8°C, the blood pressure 152/97 mm Hg, the pulse 65 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 96% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 21.7. The blood pressure decreased to 130/63 mm Hg with standing. The patient was alert and interactive. The lower jaw was held to the left, but the nasolabial folds and smile were symmetric with activation. There were nonrhythmic, nonstereotyped, writhing movements of the left arm. Tone was normal, and strength was assessed as 5 out of 5 in the arms and legs. Results of liver-function and kidney-function tests were normal, as were blood levels of glucose and electrolytes, except for the sodium level, which was 125 mmol per liter. The lactate level was 2.1 mmol per liter (19 mg per deciliter; reference range, 0.5 to 2.0 mmol per liter [5 to 18 mg per deciliter]). The urinalysis was normal. Intravenous fluids were administered. Imaging studies were obtained.

Dr. Rajiv Gupta: Computed tomographic (CT) angiography of the head and neck (Figure 1B) revealed extensively calcified plaque with severe stenosis of the distal right common carotid artery (CCA), extending into the proximal right internal carotid artery (ICA), as well as stenosis of the right and left paraclinoid ICAs and the left vertebral artery at its origin. There was no vascular abnormality on the CT angiogram that corresponded to the abnormality in the right middle frontal gyrus seen on the previous MRI.

Dr. Chui: The patient was admitted to the hospital. On the second hospital day, the sodium level had increased to 130 mmol per liter, and the lactate level was normal. Additional imaging studies were obtained.

Dr. Gupta: MRI of the head showed no evidence of acute infarction. The focus of enhancement in the right frontal lobe that had been noted previously was not seen on the current MRI.

Dr. Chui: Blood levels of thyrotropin, cobalamin, and glycated hemoglobin and results of coagulation tests were normal. Screening tests for Lyme disease, tuberculosis, and syphilis were negative, as were tests for antibodies to cardiolipin and β₂-glycoprotein. A test for antinuclear antibodies was positive, at a titer of 1:160 in a homogeneous pattern. During a physical therapy session, the patient had abnormal movements of the left leg, left arm, and left side of the face. The abnormal movements diminished when the patient used distraction techniques, such as thigh tapping, finger snapping, and walking while holding a glass of water.

The transient unresponsiveness that led to the patient’s admission was attributed to a combination of sedation from clobazam and hypovolemia. Treatment with clobazam was stopped, and hydration was encouraged. A diagnosis of functional neurologic disorder was considered; outpatient physical therapy with continued use of distraction techniques was recommended. The patient was discharged home on the third hospital day.

Episodes of involuntary movements continued to occur on a daily basis at home. Two weeks after discharge, when the patient was doing exercises while sitting in a chair and having a conversation with his wife, he suddenly stopped talking. She found him slumped in the chair with his eyes closed, no longer exercising. When she asked him questions, he repeatedly said “yes.” Emergency medical services were called, and when they arrived, the patient was alert, diaphoretic, and nonverbal. He had a facial droop on the left side and a right gaze preference. The fingerstick blood glucose level was 130 mg per deciliter (7.2 mmol per liter) and the blood pressure 120/60 mm Hg. The patient was transported to the emergency department of this hospital for further evaluation.

In the emergency department, the temporal temperature was 36.6°C, the blood pressure 143/63 mm Hg, the pulse 66 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while the patient was breathing ambient air. He was alert and interactive. There was a facial droop on the left side. There was no effort against gravity in the left arm. The patient was able to lift the left leg off the bed for 1 to 2 seconds. He had a right gaze deviation that could not be overcome and mild dysarthria. The remainder of the examination was normal. A diagnosis of stroke was considered, and emergency CT angiography was performed.

Dr. Gupta: CT angiography showed no evidence of acute territorial infarction and no changes in cerebrovascular disease.

Dr. Chui: On repeat physical examination performed after CT angiography, the gaze deviation and dysarthria had resolved, and strength was normal. Mild facial paralysis was present.

A diagnosis was made.

Differential Diagnosis

Dr. Albert Y. Hung: This 79-year-old man initially presented with involuntary movements of the left shoulder and face without associated loss of consciousness. Diagnosis of an unusual movement disorder, especially one that is present episodically, can be challenging. Videos brought in by the patient can be very useful.¹ Most movement disorders result from abnormal functioning of extrapyramidal circuits involving the basal ganglia, rather than a specific neuroanatomical lesion, and the first step toward diagnosis is to identify the type of abnormal movements.²

Four salient aspects of this patient’s involuntary movements can help in characterizing the movement disorder before generating a differential diagnosis. First, the movements were paroxysmal, lasting for short periods of time with resolution between episodes. Second, the movements were nonstereotyped, appearing randomly and variably. Third, the movements were restricted to the left side of his body throughout the course, localizing the disease process to the right cerebral hemisphere. Finally, the symptoms were progressive, increasing in both duration and frequency.

Movement Disorders

This patient had abnormal involuntary movements, symptoms indicative of a hyperkinetic movement disorder. Tremor, the most common hyperkinetic disorder, is unlikely because the patient did not have rhythmic movements. Dystonia is also unlikely, because he did not have sustained muscle contractions that were causing twisting or abnormal postures of the legs, arms, head, neck, or face. Although the patient initially described the movements as twitching, his later descriptions are not suggestive of myoclonus or tics, which manifest as sudden, rapid, recurrent movements.

This patient’s neurologist described the involuntary movements as “choreoathetoid” after reviewing a video of an episode. Chorea, athetosis, and ballism make up a spectrum of involuntary movements that often occur in combination. Chorea refers to involuntary movements that are “dancelike” — irregular, random, unintended, and flowing from one body part to another. When these movements are slow and writhing (with a lower amplitude) and involve the distal limbs, the term athetosis is used. The presence of both chorea and athetosis in the same patient is referred to as choreoathetosis. When the movements are fast and flinging (with a higher amplitude) and involve the proximal limbs, the term ballism is used. Although the description of this patient’s movements was not clearly suggestive of ballism, hemichorea and hemiballismus often occur together.

The term dyskinesia can refer to any abnormal movements and is often used to describe hyperkinetic disorders that are induced by specific drugs, such as tardive dyskinesia induced by dopamine antagonists or dyskinesia induced by levodopa in patients with Parkinson’s disease. Often, dyskinesia manifests as chorea or choreoathetoid movements, but chorea and dyskinesia are not synonymous. This patient appears to have involuntary dyskinesia with choreoathetosis as the primary phenomenology. Before constructing a differential diagnosis for dyskinesia in this patient, I will consider two conditions that mimic dyskinesia: seizures and functional movement disorder.

Seizures

Various movement disorders may be mistaken for seizures, although these movement disorders are not associated with EEG abnormalities during the episode. Patients with some forms of epilepsy may present with abnormal movements without other features that are typically associated with seizures, such as aura, change in responsiveness, incontinence, or a postictal state.^3,4 Seizures were initially suspected in this patient, and he was referred to the epilepsy clinic. Recurrent focal seizures were probably suspected because of the transient nature of the episodes. Initial MRI had shown a small abnormality in the right middle frontal gyrus, but this finding was not seen on follow-up imaging, which makes it unlikely to be related to the overall presentation. Baseline EEG had shown only brief left temporal slowing, without epileptiform abnormalities. The EEG was an interictal study, so the findings do not rule out seizures. However, the slowing was ipsilateral to the abnormal movements, so it is unlikely to be related to the episodes. In addition, the patient’s involuntary movements were nonstereotyped and nonrhythmic, which makes his presentation unlikely to be due to a seizure disorder.

Functional Movement Disorder

Because this patient’s movements diminished with the use of distraction techniques, a diagnosis of functional movement disorder was considered. Most cases of functional movement disorder begin abruptly after a trigger, such as a mild physical injury or illness; a psychological stressor can be present but is not required for diagnosis. Symptoms are typically most severe around the time of onset and may wax and wane over time. Although distractibility is a finding associated with functional disorders, abnormal movements that occur with nonfunctional syndromes can sometimes be suppressed by action or incorporated into voluntary movements in a manner that may appear distractible. Several clinical features in this patient make a diagnosis of functional disorder unlikely. Functional movement disorder is more common in women than in men, and the average age at onset is 40 years.⁵ In addition, tremor is the most common clinical phenotype seen in patients with functional movement disorder; chorea or choreoathetosis, which was seen in this patient, is very unusual in patients with functional movement disorder. Overall, functional movement disorder is unlikely to explain this patient’s presentation.

Dyskinesia

Primary paroxysmal dyskinesia refers to a group of heterogeneous syndromes characterized by recurrent involuntary movements that occur episodically and abruptly, without loss of consciousness.⁶ These disorders usually begin in childhood or young adulthood. Both the age of this patient and the described phenomenology make a diagnosis of primary paroxysmal dyskinesia unlikely.

The differential diagnosis in this case is therefore focused on causes of secondary dyskinesia, of which there are many.⁷ MRI ruled out the presence of a mass lesion suggestive of cancer. The patient had no history of acute illness suggestive of a viral or other infectious encephalitis, and there was no history of trauma or exposure to drugs or other toxins. Although his daughter mentioned trouble with memory, there was no compelling history suggestive of a neurodegenerative disease.

A common metabolic cause of secondary dyskinesia is diabetic striatopathy, a syndrome involving the acute-to-subacute onset of chorea and ballism in the context of hyperglycemia.⁸ This syndrome can occur as the initial manifestation of type 2 diabetes mellitus or as a complication of poorly controlled diabetes. Diabetic striatopathy is more likely to develop in women than in men, and the average age at onset is 70 years. Most patients present with hemichorea and hemiballismus, rather than bilateral symptoms. CT shows hyperdensity, and T1-weighted MRI shows hyperintensity, in the contralateral basal ganglia. However, this patient had no history of diabetes and had a normal blood glycated hemoglobin level, features that rule out a diagnosis of diabetic striatopathy.

Choreiform movements can also be a manifestation of autoimmune conditions.⁹ This patient’s initial presentation with unilateral shoulder and face movements would have suggested the possibility of faciobrachial dystonic seizures associated with anti–leucine-rich, glioma-inactivated 1 (anti-LGI1) encephalitis.¹⁰ This condition is often associated with hyponatremia, which was present in this patient. However, as the case evolved, leg involvement and sensory changes developed that would be atypical for anti-LGI1 encephalitis.

One key clue in this case is that the patient did not have an isolated movement disorder. In addition to motor symptoms, he had a variety of sensory symptoms involving both the left arm and the left leg. His first hospital admission was precipitated by an episode of unresponsiveness. The clinical event that led to his second presentation to the emergency department was distinctly different: an acute onset of speech difficulty accompanied by left hemiparesis and right gaze deviation that was worrisome for an acute right middle cerebral artery (MCA) syndrome. The symptoms resolved without intervention, which indicates that he may have had an acute transient ischemic attack (TIA). The most relevant imaging finding was severe cerebrovascular disease, including severe stenosis of the distal right CCA and proximal right ICA. Could this patient’s movement disorder be explained by a vascular lesion?

Limb-Shaking TIAs

Limb-shaking TIAs were first described by C. Miller Fisher in 1962.¹¹ In most case reports, these episodes are associated with high-grade stenosis of the ICA, which was seen in this patient.^12,13 The mechanism is thought to be cerebral hypoperfusion, and changes in posture or head position that decrease cerebral blood flow can precipitate these episodes. In this patient, the first episode of unresponsiveness that led to hospital admission occurred when he was sitting. He then had an acute episode involving right gaze preference that was provoked by exercise and was very suggestive of a TIA in the right MCA territory. These findings are highly suggestive of a diagnosis of limb-shaking TIAs, and I would refer this patient for emergency carotid endarterectomy.

Clinical Impression and Initial Management

Dr. Scott B. Silverman: When I evaluated this patient, his transient right gaze preference and left hemiparesis were consistent with a right MCA syndrome due to a TIA from symptomatic severe stenosis of the right ICA. The mechanism of this event was either artery-to-artery embolism or hypoperfusion. His previous, recurrent episodes of transient choreoathetosis on the left side that had occurred mainly while he was sitting, standing, or exercising were consistent with limb-shaking TIAs from hypoperfusion or low flow.

The pathogenesis of a low-flow state related to severe carotid stenosis resulting in limb-shaking TIAs is described in a small case series.¹⁴ In six out of eight patients, the transient, stereotyped, involuntary movements were eliminated with carotid artery revascularization. Positional cerebral ischemia in patients without orthostatic hypotension has been described.¹⁵

Treatment with atorvastatin was continued, the dose of aspirin was increased to 325 mg per day, and an intravenous heparin infusion was started. The strategy of permissive hypertension was used, with high blood pressure allowed to a maximum systolic blood pressure of 180 mm Hg. The patient was admitted to the stroke service, and carotid artery duplex ultrasonography was performed.

Dr. Gupta: Doppler ultrasonography of the carotid arteries (Figure 2) revealed markedly elevated Doppler flow velocities within the proximal right ICA. There was a parvus et tardus waveform in the distal right ICA, a finding indicative of low flow related to the more proximal high-grade stenosis. The Doppler waveform contours had poststenotic turbulence.

Figure 2

Doppler Ultrasound Image.

Dr. Silverman: The vascular surgery service was consulted, and the patient underwent right carotid endarterectomy.

Clinical Diagnosis

Limb-shaking transient ischemic attacks.

Dr. Albert Y. Hung’s Diagnosis

Limb-shaking transient ischemic attacks due to severe carotid stenosis, with secondary paroxysmal dyskinesia.

Pathological Discussion

Dr. Caroline F. Hilburn: The endarterectomy specimen included the carotid bifurcation and was notable for firm arterial walls, a finding consistent with calcification. On gross examination (Figure 3A), a large plaque was centered at the carotid bifurcation and protruded into the lumen, resulting in a maximal luminal stenosis of 80%. The plaque had an irregular and focally friable surface. On microscopic examination (Figure 3B), the plaque was characterized by extensive calcification. Some regions of the plaque had a smooth, healed fibrous cap, whereas other regions had an irregular surface suggestive of ulceration, which indicated potential sites of plaque rupture. Multiple smaller calcified plaques were present, affecting both branches of the artery.

Figure 3

Endarterectomy Specimen.

Pathological Diagnosis

Complex atherosclerotic plaque with portions of attached media.

Additional Management

Dr. Silverman: After the procedure, the patient had an uneventful recovery and was discharged home on the fifth hospital day. He was seen 1 month after discharge in the stroke prevention clinic. There had been no further episodes of involuntary movements or choreoathetosis and no stroke or TIA. The patient continues to take aspirin, atorvastatin, and antihypertensive medications.

Final Diagnosis

Limb-shaking transient ischemic attacks.

病例28-2024：一名75岁女性，患有水肿、关节炎和蛋白尿

以下内容来源于新英格兰医学杂志。

Presentation of Case

Dr. Christine M. Parsons (Medicine): A 75-year-old woman was evaluated at this hospital because of arthritis, abdominal pain, edema, malaise, and fever.

Three weeks before the current admission, the patient noticed waxing and waning “throbbing” pain in the right upper abdomen, which she rated at 9 (on a scale of 0 to 10, with 10 indicating the most severe pain) at its maximal intensity. The pain was associated with nausea and fever with a temperature of up to 39.0°C. Pain worsened after food consumption and was relieved with acetaminophen. During the 3 weeks before the current admission, edema developed in both legs; it had started at the ankles and gradually progressed upward to the hips. When the edema began to affect her ambulation, she presented to the emergency department of this hospital.

A review of systems that was obtained from the patient and her family was notable for intermittent fever, abdominal bloating, anorexia, and fatigue that had progressed during the previous 3 weeks. The patient reported new orthopnea and nonproductive cough. Approximately 4 weeks earlier, she had had diarrhea for several days. During the 6 weeks before the current admission, the patient had lost 9 kg unintentionally; she also had had pain in the wrists and hands, 3 days of burning and dryness of the eyes, and diffuse myalgias. She had not had night sweats, dry mouth, jaw claudication, vision changes, urinary symptoms, or oral, nasal, or genital ulcers.

The patient’s medical history was notable for multiple myeloma (for which treatment with thalidomide and melphalan had been initiated 2 years earlier and was stopped approximately 1 year before the current admission); hypothyroidism; chikungunya virus infection (diagnosed 7 years earlier); seropositive erosive rheumatoid arthritis affecting the hands, wrists, elbows, and shoulders (diagnosed 3 years earlier); vitiligo; and osteoarthritis of the right hip, for which she had undergone arthroplasty. Evidence of gastritis was reportedly seen on endoscopy that had been performed 6 months earlier. Medications included daily treatment with levothyroxine and acetaminophen and pipazethate hydrochloride as needed for cough. The patient consumed chamomile and horsetail herbal teas. She had no known allergies to medications, but she had been advised not to take nonsteroidal antiinflammatory drugs after her diagnosis of multiple myeloma.

Approximately 5 months before the current admission, the patient had emigrated from Central America. She lived with her daughter and grandchildren in an urban area of New England. She had previously worked in health care. She had no history of alcohol, tobacco, or other substance use. There was no family history of cancer or autoimmune, renal, gastrointestinal, pulmonary, or cardiac disease.

On examination, the temporal temperature was 37.1°C, the heart rate 106 beats per minute, the blood pressure 152/67 mm Hg, and the oxygen saturation 100% while the patient was breathing ambient air. She had a frail appearance and bitemporal cachexia. The weight was 41 kg and the body-mass index (the weight in kilograms divided by the square of the height in meters) 15.2. Her dentition was poor; most of the teeth were missing, caries were present in the remaining teeth, and the mucous membranes were dry. She had abdominal tenderness on the right side and mild abdominal distention, without organomegaly or guarding. Bilateral axillary lymphadenopathy was palpable. Infrequent inspiratory wheezing was noted.

The patient had swan-neck deformity, boutonnière deformity, ulnar deviation, and distal hyperextensibility of the thumbs (Fig. 1). Subcutaneous nodules were observed on the proximal interphalangeal joints of the second and third fingers of the right hand and on the proximal interphalangeal joint of the fourth finger of the left hand. Synovial thickening of the metacarpophalangeal joints of the second fingers was noted. There was mild swelling and tenderness of the wrists. She had pain with flexion of the shoulders and right hip, and there was subtle swelling of the shoulders and right knee. Pitting edema (3+) and vitiligo were noted on the legs. No sclerodactyly, digital pitting, telangiectasias, appreciable calcinosis, nodules, nail changes (including pitting), or tophi were present. The remainder of the examination was normal.

Figure 1

Photograph of the Hands.

The blood levels of glucose, alanine aminotransferase, aspartate aminotransferase, bilirubin, globulin, lactate, lipase, magnesium, and phosphorus were normal, as were the prothrombin time and international normalized ratio; other laboratory test results are shown in Table 1. Urinalysis showed 3+ protein and 3+ blood, and microscopic examination of the sediment revealed 5 to 10 red cells per high-power field and granular casts. Urine and blood were obtained for culture. An electrocardiogram met (at a borderline level) the voltage criteria for left ventricular hypertrophy.

Table 1

Laboratory Data.

Dr. Rene Balza Romero: Computed tomography (CT) of the chest, abdomen, and pelvis, performed after the intravenous administration of contrast material, revealed scattered subcentimeter pulmonary nodules (including clusters in the right middle lobe and patchy and ground-glass opacities in the left upper lobe), trace pleural effusion in the left lung, coronary and valvular calcifications, and trace pericardial effusion, ascites, and anasarca. The scans also showed slight enlargement of the axillary lymph nodes (up to 11 mm in the short axis) bilaterally and a chronic-appearing compression fracture involving the T12 vertebral body.

Dr. Parsons: Morphine and lactated Ringer’s solution were administered intravenously. On the second day in the emergency department (also referred to as hospital day 2), the blood levels of haptoglobin, folate, and vitamin B₁₂ were normal; other laboratory test results are shown in Table 1. A rapid antigen test for malaria was positive. Wright–Giemsa staining of thick and thin peripheral-blood smears was negative for parasites; the smears also showed Döhle bodies and basophilic stippling. Antigliadin antibodies and anti–tissue transglutaminase antibodies were not detected. Tests for hepatitis A IgG and hepatitis C antibodies were positive. Tests for hepatitis B core and surface antibodies were negative. A test for human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) was negative.

Findings on abdominal ultrasound imaging performed on the second day (Fig. 2A and 2B) were notable for a small volume of ascites and kidneys with echogenic parenchyma. Ultrasonography of the legs showed no deep venous thrombosis. An echocardiogram showed normal ventricular size and function, aortic sclerosis with mild aortic insufficiency, moderate tricuspid regurgitation, a right ventricular systolic pressure of 39 mm Hg, and a small circumferential pericardial effusion. Intravenous hydromorphone was administered, and the patient was admitted to the hospital.

Figure 2

Imaging Studies of the Abdomen and Hands.

On the third day (also referred to as hospital day 3), nucleic acid testing for cytomegalovirus, Epstein–Barr virus, and hepatitis C virus was negative, and a stool antigen test for Helicobacter pylori was negative. An interferon-γ release assay for Mycobacterium tuberculosis was also negative. Oral acetaminophen and ivermectin and intravenous hydromorphone and furosemide were administered.

Dr. Balza Romero: Radiographs of the hands (Fig. 2C through 2F) showed joint-space narrowing of both radiocarpal joints and proximal interphalangeal erosions involving both hands. Radiographs of the shoulders showed arthritis of the glenohumeral joint and alignment suggestive of a tear of the right rotator cuff. A radiograph of the pelvis showed diffuse joint-space narrowing of the left hip, without osteophytosis, and an intact right hip prosthesis.

Dr. Parsons: Diagnostic tests were performed, and management decisions were made.

Differential Diagnosis

Dr. Beth L. Jonas: This patient is a 75-year-old woman who recently emigrated from Central America. She presented to this hospital with a multisystem disease involving the respiratory, gastrointestinal, renal, and musculoskeletal systems. Her medical history is notable for seropositive erosive rheumatoid arthritis and multiple myeloma, which had been treated with melphalan and thalidomide. Relevant clinical features on presentation include unintended weight loss and cachexia, axillary lymphadenopathy, serositis, cytopenia in two cell lines, hypocomplementemia, and elevated serum free kappa and lambda light-chain levels (with a normal free light-chain ratio) with no monoclonal spike. The white-cell count was elevated, but she had no eosinophilia. CT images of the chest showed scattered subcentimeter pulmonary nodules. With respect to the patient’s anemia, no schistocytes were present, the haptoglobin level was normal, and the iron studies were unremarkable. These findings, in combination with the elevated ferritin level, indicate anemia of chronic inflammation. The renal findings are most salient in the context of the patient’s hypertension, anasarca, elevated cystatin C level, active urinary sediment with proteinuria in the nephrotic range, and small, echogenic kidneys on ultrasonography.

In constructing a differential diagnosis, I will consider medication use, cancer, infectious disease, and autoimmune disease. Medications can be eliminated as the cause of this patient’s illness, since she was taking only levothyroxine, acetaminophen, and the antitussive agent pipazethate.

Cancer

The patient has a history of multiple myeloma, which may manifest with a multisystem disease involving the kidneys, but serum protein electrophoresis showed no monoclonal protein. Given the presence of nephrotic syndrome in the context of multiple myeloma, systemic immunoglobulin light-chain amyloidosis would be highest on the differential diagnosis with respect to cancer; however, the patient’s normal light-chain ratio makes this diagnosis unlikely. The development of myeloid neoplasms, such as acute myeloid leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms, is important to consider in the context of previous treatment with alkylating agents,¹ which this patient had received. However, the peripheral-blood smear showed no findings that would indicate a hematologic cancer, and such a diagnosis would not explain the patient’s acute kidney injury with nephrotic-range proteinuria.

Infectious Disease

Several features of this patient’s case warrant special consideration, including her history of immunosuppression due to rheumatoid arthritis and to previously treated myeloma, along with the fact that she had emigrated from Central America, where certain infections may be prevalent. Infection with hepatitis A virus, hepatitis B virus, hepatitis C virus, HIV-1 and HIV-2, cytomegalovirus, Epstein–Barr virus, H. pylori, and M. tuberculosis can be ruled out on the basis of laboratory studies. A rapid antigen test for plasmodium species was reported to be positive, but this assay has a known cross-reactivity with rheumatoid factor.² Moreover, the thick and thin peripheral-blood smears were negative. Thus, malaria would be an unlikely diagnosis.

The patient has a history of infection with chikungunya virus, an arbovirus transmitted by a mosquito vector that has been responsible for large epidemics in the Americas since 2013.³ Acute symptoms include fever, rash, arthralgia, and myalgia. The development of a chronic arthritis that may meet the classification criteria for rheumatoid arthritis, as defined by the American College of Rheumatology and the European Alliance of Associations for Rheumatology, has been reported in up to 60% of patients infected with chikungunya virus.^4,5 In the context of this discussion, I considered whether chikungunya virus infection could be the cause of this patient’s symptoms, since this infection occurred before the diagnosis of rheumatoid arthritis. However, the degree of erosion and loss of joint space that was visible on radiographs would be most unusual for arthritis associated with chikungunya virus infection and would not explain the renal manifestations.

Strongyloidiasis is a helminth infection (caused by Strongyloides stercoralis) that is widespread in developing countries. Infection usually occurs through contact with soil, and most affected persons are asymptomatic. However, in immunosuppressed persons, strongyloides hyperinfection syndrome or a disseminated infection can develop as a consequence of accelerated autoinfection.⁶ The clinical presentation of strongyloides hyperinfection syndrome can include gastrointestinal symptoms (diarrhea, constipation, nausea, or vomiting), respiratory symptoms (cough, dyspnea, or wheezing), and rash due to migration of larvae through the subcutaneous tissues. Of note, only a minority of patients present with eosinophilia. Several case reports describe the development of nephrotic-range proteinuria, thrombotic microangiopathy, and IgA vasculitis in patients with strongyloides hyperinfection syndrome.^7-9 However, strongyloidiasis would not explain this patient’s cytopenias and hypocomplementemia.

Autoimmune Disease

The patient has a 3-year history of rheumatoid arthritis, although her clinical features of swan-neck deformity, boutonnière deformity, and joint instability suggest a longer duration of disease. We do not know whether she had received previous treatment with disease-modifying antirheumatic drugs or biologic agents, but the possible use of such treatments may be a consideration with respect to her progression of disease and overall degree of immunosuppression. The blood levels of rheumatoid factor and anti–cyclic citrullinated peptide antibodies were elevated, and radiographs of the hands showed erosive disease, although there was a relative paucity of metacarpophalangeal findings. A review of systems was negative for dry mouth, but her physical examination showed poor dentition and dry mouth — findings that make secondary Sjögren’s syndrome a consideration.

Renal disease can occur in patients with Sjögren’s syndrome. The two most typical presentations are tubulointerstitial nephritis and, less commonly, nephritic syndrome (membranoproliferative glomerulonephritis related to cryoglobulinemia). Tubulointerstitial nephritis may manifest with renal disease of varying severity, usually with a bland urinary sediment and often with abnormalities of tubular function such as distal renal tubular acidosis. Membranoproliferative glomerulonephritis caused by cryoglobulinemia is the most common glomerular disease associated with Sjögren’s syndrome. Although nephrotic-range proteinuria can occur with Sjögren’s syndrome, it is relatively uncommon.¹⁰ Renal disease is uncommon in patients with rheumatoid arthritis and is usually related to coexisting cardiovascular conditions. Medications used in the treatment of autoimmune disease — mainly nonsteroidal antiinflammatory drugs — may be associated with renal disease, but I would not expect the presence of an active urinary sediment, as was seen in this patient.

Amyloid A (AA) amyloidosis, a condition that is rare in the era of aggressive management of rheumatoid arthritis, has been described in patients with severe, long-standing seropositive erosive rheumatoid arthritis. Serum amyloid A (SAA) is a protein that is produced in the liver in response to chronic inflammation associated with interleukin-1, interleukin-6, and tumor necrosis factor α (TNF-α) in the context of chronic infections, autoimmune disease (classically rheumatoid arthritis), autoinflammatory disease, and cancers including renal cell carcinoma and non-Hodgkin’s lymphoma.¹¹ Signs and symptoms of AA amyloidosis are related to the deposition of the protein in organs, and patients often present with multisystem signs and symptoms. The kidney is the organ that is most often affected, but deposition can occur in the heart, gastrointestinal tract, nervous system, musculoskeletal system, and lungs. Proteinuria is the first clinical manifestation in almost 95% of patients with AA amyloidosis, and 50% of affected patients present with nephrotic syndrome.¹² The urinary sediment is generally bland, and complement levels in the blood are normal. AA amyloidosis remains on the differential diagnosis in this patient, but it would not completely explain her renal disease.

Hypocomplementemia

The key to this case is understanding the cause of this patient’s hypocomplementemia. Hypocomplementemia can be due to decreased complement production in the context of liver disease, congenital complement deficiency, or increased complement consumption resulting from activation of the innate immune system. This patient has no history of chronic liver disease and her laboratory test results indicated good hepatic synthetic function. Classical complement deficiency (including C4 deficiency) that begins early in life is associated with autoimmune disease, and early C3 deficiency is characterized by severe pyogenic infections. It would be unusual for a patient of this age to be deficient in both C3 and C4 without earlier clinical consequences. I therefore concluded that the hypocomplementemia in this case was related to complement consumption.

Rheumatic diseases that may be associated with prominent renal manifestations include antineutrophil cytoplasmic antibody–associated vasculitis, systemic sclerosis with renal crisis, cryoglobulinemic vasculitis, antiglomerular basement membrane disease, and systemic lupus erythematosus (SLE). Of those conditions, SLE would be the most likely to be manifested by an active urinary sediment and nephrotic-range proteinuria with consumption of both C3 and C4 in the context of fever, thrombocytopenia, and serositis. This patient’s fever, thrombocytopenia, and serositis also fit with this diagnosis.¹³

Because the patient has long-standing seropositive erosive rheumatoid arthritis, a diagnosis of AA amyloidosis is strongly suspected. Moreover, given the presence of thrombocytopenia, hypocomplementemia, and an active urinary sediment, I would recommend a kidney biopsy to evaluate for lupus nephritis and AA amyloidosis.

Dr. Beth L. Jonas’s Diagnosis

Overlap syndrome of rheumatoid arthritis and systemic lupus erythematosus with amyloid A amyloidosis.

Pathological Discussion

Dr. Claire Trivin-Avillach: Testing for autoimmune antibodies was performed. A test for antinuclear antibodies was positive at a titer of 1:5120 with a homogeneous pattern, and a test for anti–double-stranded DNA antibodies was positive at a titer of 1:2560.

The diagnostic procedure in this case was a core-needle biopsy of the kidney. Examination of the specimen with light microscopy revealed 20 glomeruli, 45% of which were globally sclerosed, along with fibrosis involving approximately 60% of the interstitium and tubular atrophy. Diffusely enlarged glomeruli with thickened capillary walls and an expanded mesangium were weakly positive on periodic acid–Schiff staining; the glomeruli stained pale blue on Masson’s trichrome staining. Congo red staining revealed metachromatic salmon-colored deposition involving the glomeruli, the blood-vessel walls, and the interstitium, which was associated with apple-green birefringence when viewed under polarized light (Fig. 3A). In addition, mesangial and endocapillary hypercellularity was identified in approximately 30% of the nonsclerosed glomeruli and was associated with karyorrhexis (Fig. 3B). One cellular crescent was also detected. These features are characteristic of active proliferative glomerulonephritis.

Figure 3

Biopsy Specimen of the Kidney.

Immunofluorescence microscopy revealed prominent granular staining for IgG (4+), IgM (4+), C3 (3+), C1q (3+), IgA (1+), kappa (3+), and lambda (3+) along the glomerular basement membranes and within the mesangium, as well as focal granular deposits of IgG and C3 along the tubular basement membrane (Fig. 3C and 3D). Additional immunofluorescence studies showed strong positivity (4+) for SAA within the glomeruli, the blood-vessel walls, and the interstitium (Fig. 3E), whereas staining for beta₂-microglobulin, transthyretin, and apolipoprotein A1 was faint.

Electron microscopy revealed the presence of subendothelial and mesangial electron-dense deposits (with no substructure identified) adjacent to randomly arranged fibrils (measuring 8.2 to 10.6 nm in diameter) within the glomerular basement membranes and the mesangium (Fig. 3F). Glomerular endothelial cells appeared reactive and contained tubuloreticular inclusions, features that were suggestive of interferon-mediated activation.

The findings on Congo red staining were characteristic of amyloidosis with typical birefringent material. The strong positivity of SAA within the deposits as compared with the faint staining of other reactants identified the type of amyloid as SAA, which is consistent with the patient’s history of rheumatoid arthritis. The biopsy also showed an immune complex–mediated proliferative glomerulonephritis with a “full house” pattern (defined as positivity for the three immunoglobulin classes IgG, IgM, and IgA and the two complement components C3 and C1q, in reference to the “full house” hand in a poker game). Immune complex–mediated proliferative glomerulonephritis has been reported in patients with rheumatoid arthritis who were receiving anti–TNF-α therapy,¹⁴ which was not the case in this patient. The positive test for hepatitis C antibodies prompted consideration of hepatitis C–related membranoproliferative glomerulonephritis. However, taken together, the negative nucleic acid test for hepatitis C virus, the full house pattern on immunofluorescence, the tubular basement membrane deposits, and the positive test for anti–double-stranded DNA antibodies favor a diagnosis of lupus nephritis of at least class III (defined as focal proliferative glomerulonephritis), according to the criteria of the International Society of Nephrology and the Renal Pathology Society, superimposed on AA amyloidosis.

Pathological Diagnosis

Proliferative lupus nephritis of International Society of Nephrology and Renal Pathology Society class III, superimposed on amyloid A amyloidosis.

Discussion of Management

Dr. Pui W. Cheung: On the basis of the finding of echogenic kidneys on ultrasonography and the findings of extensive interstitial fibrosis and tubular atrophy on kidney biopsy, we know that this patient has advanced chronic kidney disease that is unlikely to be reversible. The patient is also noted to have a markedly lower glomerular filtration rate (GFR) than that predicted by the blood creatinine level owing to the presence of cachexia, and this is substantiated by the cystatin C–based GFR and a 24-hour creatinine clearance of 22 ml per minute per 1.73 m² of body-surface area. The typical induction therapy for stage III or IV lupus nephritis consists of high-dose glucocorticoids and either mycophenolate mofetil or cyclophosphamide. Other reasonable alternatives for initial therapy include mycophenolate mofetil in combination with either a calcineurin inhibitor or belimumab, or cyclophosphamide in combination with belimumab.¹⁵ Hydroxychloroquine is also recommended as part of the therapy, since it has shown benefits in improving the response to treatment and reducing disease flare.¹⁶ Mycophenolate mofetil and cyclophosphamide have similar efficacy with respect to clinical response, which includes a reduction in proteinuria and either an improvement in renal function or stabilization of renal function; the risks of infections and adverse events associated with these medications are also similar.^17,18

Given the severity of the lupus nephritis with overlying AA amyloidosis from active rheumatoid arthritis, the treatment options proposed were high-dose glucocorticoids and rituximab with either mycophenolate mofetil or cyclophosphamide.¹⁹ After discussions with multidisciplinary consultants from rheumatology, infectious diseases, and nephrology, lingering concerns were raised about infection and patient frailty; ultimately, the decision was made to initiate high-dose glucocorticoid therapy in combination with mycophenolate mofetil, rituximab, and hydroxychloroquine.

The patient’s mycophenolate mofetil dose regimen was inconsistent owing to gastrointestinal side effects, and the treatment was eventually withheld because of pancytopenia and fever. Unfortunately, her kidney function worsened, and renal replacement therapy was initiated within 3 weeks after the start of the induction therapy. The cause of her renal failure was thought to be disease progression, compounded by hemodynamically mediated tubular injury in the context of infection. While the administration of mycophenolate mofetil was stopped, treatment with rituximab was continued, with slow tapering of the glucocorticoid dose at the direction of the rheumatologist. She remained dependent on dialysis and was deemed to have end-stage kidney disease after 3 months of dialysis.

Dr. Lisa G. Criscione-Schreiber: The patient has SLE with nephritis, seropositive erosive rheumatoid arthritis, and systemic AA amyloidosis. AA amyloidosis is rare owing to the availability of effective therapies for rheumatoid arthritis and is managed through aggressive treatment of inflammation due to rheumatoid arthritis. Reports addressing the management of rheumatoid arthritis–induced AA amyloidosis generally cite stability of end-organ damage caused by AA amyloid as evidence of effective management of the condition (through treatment of the inflammation of rheumatoid arthritis). Methotrexate, the cornerstone of treatment for rheumatoid arthritis, is contraindicated in this case owing to the presence of kidney disease. The alkylating agent cyclophosphamide has been reported to be effective for the treatment of AA amyloidosis from rheumatoid arthritis²⁰ and has known efficacy in patients with lupus nephritis, both of which make it a viable treatment option. Rituximab has also been reported to be effective for managing rheumatoid arthritis–induced AA amyloidosis,²¹ is approved for the treatment of rheumatoid arthritis, and is used for manifestations of SLE, including thrombocytopenia and nephritis. Although anti–TNF-α agents, abatacept, and Janus kinase inhibitors are reported to be effective for the treatment of AA amyloidosis in patients with rheumatoid arthritis,²² recent publications have coalesced on the ability of anti–interleukin-6 therapy to block interleukin-6–induced hepatic production of SAA.^23-25

The overlap of seropositive erosive rheumatoid arthritis and SLE (sometimes termed “rhupus”) usually resembles rheumatoid arthritis more than SLE; manifestations include thrombocytosis, leukocytosis, an elevated erythrocyte sedimentation rate, an elevated blood level of C-reactive protein, and the presence of marginal erosions on radiographs.²⁶ In contrast, SLE without seropositive erosive rheumatoid arthritis characteristically manifests with thrombocytopenia, leukopenia, and an elevated erythrocyte sedimentation rate but usually not an elevated C-reactive protein level; in addition, nonerosive inflammatory arthritis with reversible deformities is commonly observed. This patient had a mixed laboratory profile, on the basis of the results of antinuclear antibody and anti–double-stranded DNA antibody tests. The challenge of treating an overlap syndrome of rheumatoid arthritis and SLE is choosing disease-modifying antirheumatic drugs that are effective and safe in both conditions. This patient’s most severe disease manifestation is lupus nephritis; therefore, the treatment regimen must target nephritis along with the AA amyloidosis and inflammatory arthritis.

As noted earlier, current induction therapy for lupus nephritis includes either mycophenolate mofetil or cyclophosphamide. Mycophenolate mofetil may provide inadequate treatment of the rheumatoid arthritis and amyloidosis, whereas cyclophosphamide would treat the lupus nephritis, has possible efficacy for treatment of the AA amyloidosis, and would treat the rheumatoid arthritis. Rituximab could be added to cyclophosphamide or mycophenolate mofetil to treat the rheumatoid arthritis and resultant AA amyloidosis and could also possibly help treat the lupus nephritis. The addition of anti–interleukin-6 therapy to mycophenolate mofetil or cyclophosphamide is an intriguing option that may effectively treat the rheumatoid arthritis and subsequent AA amyloidosis. The addition of belimumab to mycophenolate mofetil or cyclophosphamide has been reported to improve renal response in patients with lupus nephritis,²⁷ as has the addition of voclosporin to mycophenolate mofetil.²⁸ However, belimumab is ineffective for the treatment of rheumatoid arthritis, and voclosporin has not been studied in patients with rheumatoid arthritis or in those with a GFR of 45 milliliters per minute or less. The high-dose glucocorticoids that are used in induction therapy for lupus nephritis will effectively manage this patient’s inflammatory arthritis and probably also the subsequent AA amyloidosis. Finally, it is important that every patient with lupus nephritis receive hydroxychloroquine, which improves the treatment response to induction therapy.²⁹

Follow-up

Dr. Parsons: The patient’s hospital course was further complicated by suspected immune-mediated thrombocytopenia, for which she received intravenous immune globulin. Her pancytopenia and arthritis ultimately abated. Unfortunately, she did not have renal recovery and continues to receive hemodialysis. After a prolonged hospital course, she was discharged home.

Final Diagnosis

Overlap syndrome of rheumatoid arthritis and systemic lupus erythematosus complicated by proliferative lupus nephritis, superimposed on amyloid A amyloidosis.

戈沙妥珠单抗（SG）用于HR+/HER2−转移性乳腺癌：3期试验EVER-132-002结果

以下内容来源于PubMed。

Abstract

Sacituzumab govitecan (SG) significantly improved progression-free survival (PFS) and overall survival (OS) versus chemotherapy in hormone receptor-positive human epidermal growth factor receptor 2-negative (HR⁺HER2^-) metastatic breast cancer (mBC) in the global TROPiCS-02 study. TROPiCS-02 enrolled few Asian patients. Here we report results of SG in Asian patients with HR⁺HER2^- mBC from the EVER-132-002 study. Patients were randomized to SG (n = 166) or chemotherapy (n = 165). The primary endpoint was met: PFS was improved with SG versus chemotherapy (hazard ratio of 0.67, 95% confidence interval 0.52-0.87; P = 0.0028; median 4.3 versus 4.2 months). OS also improved with SG versus chemotherapy (hazard ratio of 0.64, 95% confidence interval 0.47-0.88; P = 0.0061; median 21.0 versus 15.3 months). The most common grade ≥3 treatment-emergent adverse events were neutropenia, leukopenia and anemia. SG demonstrated significant and clinically meaningful improvement in PFS and OS versus chemotherapy, with a manageable safety profile consistent with prior studies. SG represents a promising treatment option for Asian patients with HR⁺HER2^- mBC (ClinicalTrials.gov identifier no. NCT04639986 ).

压力导致亚精胺增多并抑制树突状细胞中1型干扰素（IFN-α）诱发腹泻型肠易激综合征

以下内容来源于PubMed。

Abstract

Irritable bowel syndrome with diarrhea (IBS-D) is a common and chronic gastrointestinal disorder that is characterized by abdominal discomfort and occasional diarrhea. The pathogenesis of IBS-D is thought to be related to a combination of factors, including psychological stress, abnormal muscle contractions, and inflammation and disorder of the gut microbiome. However, there is still a lack of comprehensive analysis of the logical regulatory correlation among these factors. In this study, we found that stress induced hyperproduction of xanthine and altered the abundance and metabolic characteristics of Lactobacillus murinus in the gut. Lactobacillus murinus-derived spermidine suppressed the basal expression of type I interferon (IFN)-α in plasmacytoid dendritic cells by inhibiting the K63-linked polyubiquitination of TRAF3. The reduction in IFN-α unrestricted the contractile function of colonic smooth muscle cells, resulting in an increase in bowel movement. Our findings provided a theoretical basis for the pathological mechanism of, and new drug targets for, stress-exposed IBS-D.

Keywords: AdorA2B; Lactobacillus murinus; irritable bowel syndrome with diarrhea; spermidine; stress; type I interferon; xanthine.

婴儿重症细支气管炎的鼻咽部宏基因组与哮喘遗传风险亚型联合分析及其与儿童哮喘风险的相关性

以下内容来源于PubMed。

Abstract

The severe bronchiolitis endotype characterized by a high abundance of H. influenzae, high proportion of RV-A and RV-C infections, and high asthma genetic risk had a significantly higher risk for developing asthma.

Background: Infants with bronchiolitis are at increased risk for developing asthma. Growing evidence suggests bronchiolitis is a heterogeneous condition. However, little is known about its biologically distinct subgroups based on the integrated metagenome and asthma genetic risk signature and their longitudinal relationships with asthma development.

Methods: In a multi-center prospective cohort study of infants with severe bronchiolitis (i.e., bronchiolitis requiring hospitalization), we profiled nasopharyngeal airway metagenome and virus at hospitalization, and calculated the polygenic risk score of asthma. Using similarity network fusion clustering approach, we identified integrated metagenome-asthma genetic risk endotypes. We also examined their longitudinal association with the risk of developing asthma by age six years.

Results: Of 450 infants with bronchiolitis (median age, 3 months), we identified five distinct endotypes-characterized by their nasopharyngeal metagenome, virus, and asthma genetic risk profiles. Compared with endotype A infants (who clinically resembled "classic" bronchiolitis), endotype E infants (characterized by a high abundance of H. influenzae, high proportion of RV-A and RV-C infections, and high asthma genetic risk) had a significantly higher risk for developing asthma (35.9% versus 16.7%; OR_adj, 2.24; 95%CI, 1.02-4.97; p=0.046). The pathway analysis showed that endotype E had enriched microbial pathways (e.g., glycolysis, L-lysine, arginine metabolism) and host pathways (e.g., IFNs, IL-6/JAK/STAT3, fatty acids, MHC, and immunoglobin-related) (FDR<0.05). Additionally, endotype E had a significantly higher proportion of neutrophils (FDR<0.05).

Conclusion: In this multi-center prospective cohort study of infant bronchiolitis, the clustering analysis of integrated-omics data identified biologically distinct endotypes with differential risks for developing asthma.

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