简介:

广西医科大学第二附属医院（第二临床医学院）是广西医科大学直属附属医院，成立于2003年3月27日，同年10月9日并入广西医科大学第一附属医院，更名为广西医科大学第一附属医院西院（为延伸管理的院区），2017年1月1日重新独立运营管理。经过六年的建设与发展，医院整体综合实力快速提升，区域辐射能力明显增强，行业地位和社会声誉显著提高，已成为集医疗、教学、科研、保健及康复为一体的三级甲等综合性医院，是广西重要的优质医疗资源和广西医科大学主要的临床教学基地，是国家药物临床试验机构（呼吸、消化、心血管、肾病、内分泌、免疫、放射治疗、肿瘤、血液、器官移植共10个专业）、通过中国胸痛中心、国家级卒中中心认证单位、获中国县域医院院长联盟批准为“共建县域医院综合能力提升培训基地”（全国首家）、中国肺癌防治联盟结节诊治分中心、国家首批疼痛质控中心哨点医院、广西首家航空医学救援基地医院、广西航空医学救援培训基地、广西首家“全民健康管理示范医院”、国家第一批肿瘤（消化系统）多学科诊疗试点医院、广西急救医学质量控制中心、广西疼痛医学质量控制中心的挂靠单位、广西首家“血友病治疗中心”、广西呼吸系统疾病临床医学研究中心、广西器官移植临床医学研究中心、广西壮族自治区新增残疾儿童康复救助人工耳蜗手术定点医院、国内首家通过DNV国际医院标准认证的公立综合医院、广西首家通过ISO15189医学实验室质量和能力认可的自治区级医院、广西唯一临床营养建设示范单位。医院先后荣获2017年度国家卫计委“改善医疗服务示范医院”、2018年度国家级“管理创新医院”、2019年“自治区卫生系统集体二等功医院”、2019年“全国人文爱心医院”，2020年国家卫生健康委、中央政法委等十部委联合授予的全国平安医院工作表现突出集体称号、2019-2020年度“全国医院医疗保险服务规范先进单位”、2020年度国家卫健委“改善医疗服务示范医院”“改善医疗服务十大亮点单位”（广西唯一获此殊荣的医院），标准化、精细化管理案例荣获2021年中南六省（区）医院院长高峰论坛医院管理创新奖一等奖，2022年荣获广西援沪抗击新冠肺炎疫情先进集体称号等荣誉。一、医院环境与规模医院位于南宁市西乡塘区的相思湖畔大学东路166号，毗邻高新技术开发区，周边高校云集，环境优美，交通便利，区域医疗资源薄弱，具有得天独厚的地域优势。占地面积158亩，总建筑面积185532.55㎡。实际开放床位1909张，现设有33个临床科室，48个病区，37个专科门诊、12个医技科室，设有临床技能模拟训练中心、临床医学研究中心、遗传与基因组医学中心、高新工业园社区卫生服务中心，提供特色专病门诊、疑难病多学科会诊等诊疗服务。2022年门急诊患者超过115万人次，出院患者近5万人次，手术2.2万台次。医院新建成的病房医技综合楼于2022年12月26日正式投入使用，同时正规划建设自治区突发急性传染病临床救治中心。二、人才队伍与结构截至目前，医院职工3068人，其中医师739人，护士1178人，医技人员210人，药学人员75人，卫生技术人员占全院技术人员比例为89.4%。卫生技术人员中，正高职称132人，副高职称201人，学科首席和特聘专家17人，医师队伍中博士110人（另有职工在读博士70人），硕士565人，博士生导师17人，硕士生导师109人，医生中具有硕士以上学历比例近91.4%。拥有广西“十百千人才工程”1名，广西医学高层次人才7名，二级教授7名，人才队伍迅速壮大。国家级学（协）会副会长2人，主任委员2人，常务理事1人、副主任委员5人、常务委员27人；省级学（协）会主任委员33人、副主任委员96人，常务委员146人、常务理事18人。三、学科建设与优势医院学科设置齐全，技术力量雄厚，综合实力排在自治区前列。与广西医科大学第一附属医院共享国家临床重点专科6个（重症医学科、急诊医学科、呼吸与危重症医学科、普通外科、肿瘤科、临床护理专业），拥有广西临床重点专科建设项目12个（内分泌科、康复医学科、精神科、血液内科、医学影像科、医学检验科、创伤外科、呼吸与危重症医学科、普通外科、耳鼻咽喉头颈外科、风湿免疫科、心胸外科），拥有广西临床重点专科培育项目2个（泌尿外科、病理科），广西医疗卫生重点学科12个（心血管内科、儿科、麻醉科、重症医学科、呼吸内科、急诊医学科、康复医学科、肿瘤内科、骨科、神经内科、消化内科、心胸外科），广西医疗卫生重点培育学科2个（普通外科、产科）。移植医学中心具有肝脏、肾脏、心脏、肺脏、胰腺5个种类器官移植执业资质。特色优势学科－急诊科是广西医学救援协会会长单位、广西航空医学救援培训基地和广西航空医学救援联盟会长单位，应急救援力量强大，2018年牵头成立中国—东盟医院合作联盟急诊专科跨境医联体，承担着区域内重大突发公共卫生事件的救治任务。医院共组建7个专科/专病联盟，其中包括胆胰疾病内镜诊治专科联盟、食管胃底静脉曲张内镜治疗专科联盟、内痔内镜微创治疗专科联盟、康复医学合作发展联盟、疼痛专科联盟、眩晕联盟、航空医疗救援专科联盟，共有联盟成员单位490个。医院“自治区突发急性传染病临床救治中心”获批列为自治区重大疫情救治基地建设项目（2021-2023年）。打造多个品牌医疗中心（移植医学中心、微创外科中心、创伤急救中心、肺癌诊疗中心、遗传与基因组医学中心、精神卫生与康复中心、卒中中心、疾病健康管理中心等），不断完善多学科协作的综合治疗体系，不断强化学科建设。四、医疗技术与特色在提供全面医疗保健服务前提下，形成以重点学科为引领的特色医疗体系，特别是移植医学中心年捐献器官移植量超500例，在肝移植、肾移植、肝肾联合移植、胰肾联合移植、捐献器官功能评估与修复、移植围手术期处理、移植重症等专业领域处于国际先进、国内领先水平，器官移植手术量位居国内前列。创伤急救、微创外科、心脏射频消融、呼吸内科气管内介入诊疗、眩晕症外科治疗、气管－食道瘘等复杂瘘修补、消化内镜诊疗、危重症救治（ECMO技术）、心理疾病早期规范化诊疗、小儿脑瘫与重症康复、各种慢性及顽固性疼痛治疗等多项特色技术处于区内领先、国内先进水平。五、主要设备与平台拥有大批高精尖医疗设备，包括西门子PET/CT、飞利浦显微256CT、GE与西门子3.0T磁共振、瓦里安VitalBeam直线加速器、迈柯维ECMO、STORZ一体化手术室、GEIGS530数字减影血管造影机（DSA）、贝克曼大型全自动生化分析仪、高档彩色多普勒超声仪、进口腹腔镜、OLYMPUS电子胃镜与支气管镜、立体定向导航手术系统、共焦激光眼底扫描系统、人工心肺系统、医用空气加压氧舱、广西区内首台世界领先的颈腰痛治疗设备——非手术脊柱减压系统IDD、手术实时转播系统等，是全国首家（飞利浦）“规范化影像检查质控培训基地”和广西首家“绿色CT扫描中心”。六、医学教育与培训医院临床医学专业是一级学科硕士、博士学位授权点，是国家住院医师规范化培训基地、首批专科医师规范化培训基地（普通外科）；临床技能模拟训练中心是国家医学考试中心医师资格考试临床类别分阶段考试第一、第二阶段实证研究基地、美国心脏协会（AHA）心血管急救培训中心、广西住院医师规范化培训结业考核基地，可满足多学科、多层次技能培训需求。目前，承担临床医学、麻醉、康复、精神、护理等专业实习、全日制研究生（硕士、博士）的临床轮转及科研指导工作，同时，积极承接东盟留学生教学工作，已接收东盟国家留学生120多名。七门课程已在“国家高等教育智慧教育平台”上线；《临床技能学》课程入选自治区级线上一流本科课程、线上线下混式一流本科课程、《儿科学》入选自治区级线上线下混式一流本科课程。七、科研学术与实力医院致力于医教研协同发展，推动医教进步的同时，致力于提升科研实力，获批省级重点实验室1个：广西移植医学工程技术中心（共建）。省级临床医学研究中心2个：广西呼吸系统疾病临床研究中心、广西器官移植临床医学研究中心。自治区卫生健康委重点实验室3个：广西器官捐献与移植研究重点实验室、广西医学遗传与基因组学研究重点实验室、广西急危重症医学重点实验室（重点培育）。先后建立科研平台4个（医院临床医学研究中心、联合生命科学研究中心、广西医科大学第二附属医院－加拿大神经精神疾病重点实验室、广西医科大学第二附属医院－美国密西西比大学药理学与毒理学联合实验室）。五年以来，科研立项920余项（其中国家自然科学基金22项），发表论文2300余篇（其中高水平论文953篇），科研获奖27项（其中广西科学技术奖二等奖1项、三等奖3项），获得国家专利授权370余项。八、国际交流与合作医院包容并蓄，国际合作日趋活跃。已连续成功举办三届“中国－东盟国际急诊医学高峰论坛”、两届“中国－东盟卫生应急合作论坛”，牵头成立中国－东盟医院合作联盟急诊专科跨境医联体、环南海-中国东盟海上医学救援联盟，初步形成东盟辐射网络。与美国克利夫兰医学中心、密西西比大学医学中心、上海复旦大学中山医院、国家“双一流”高校电子科技大学等多家国内外单位开展跨区域学科合作，为人才培养搭建交流平台。牵头编纂出版《广西（东盟）航空医学救援培训手册》，填补了中国航空医学救援方面参考用书空白，是国内首部航空医学救援实操性指导用书。九、社会服务与责任医院始终将公益性摆在突出地位，勇于承担社会责任。认真开展紧密型医联体建设与对口支援工作，积极推动优质医疗资源下沉和共享，已帮助开展新技术、新业务达171项，建立远程医疗协作关系，开展远程会诊，在高质量推进健康扶贫和出色完成自治区重大医疗保障任务中体现二附院人的责任与担当。积极贯彻党中央关于新冠肺炎疫情防控部署，先后派出自治区级专家、医疗队员前往湖北、上海、香港、贵州、桂林、北海、河池、崇左、百色、龙州等地区支援疫情救治及核酸检测工作，出色完成各项疫情防控和救治任务。牵头完成自治区抗疫科研重大攻关项目，为抗击疫情提供“广西方案”、贡献广西智慧和力量。全院荣获3项全国先进个人表彰、1项全国先进集体、7项自治区级个人荣誉，得到国家、自治区卫生系统和广大人民群众的充分肯定。医院是中国县域医院院长联盟县域医院综合能力提升基地（全国首家，广西唯一）。是广西首家开启“黄昏门诊”的医院。十、医院文化与愿景医院始终坚持“文化建院依法治院科教兴院人才强院”的办院宗旨，遵循“仁爱、至诚，求实、至臻”的院训，深耕“患者至上员工为本”的服务理念，牢记使命担当，砥砺前行赶超跨越，全力将医院建设成为具有一流管理、一流技术、一流服务、一流环境的现代化医院，力争特色优势学科进入全国先进行列，达到国内一流水平，努力将医院打造成为具有一定国际影响力、区域高水平的医科大学附属医院，为人民群众提供高品质的卫生与健康服务。垂体前叶功能减退症系腺垂体分泌激素不足所引起的征群。本病可分为部分性与完全性二类,前者受累激素仅1～7种;后者则为全部垂体前叶激素合成与分泌不足，任何引起垂体前叶或下丘脑破坏的损伤均可引起垂体前叶功能减退症，垂体，治疗的方向在于使功能减退的靶腺的激素得到替代，不确定，无，实验室检查，。

true 袁海宁主任医师

三级甲等广西医科大学第二附属医院

好评率：100% 接诊量：117 平均响应：10小时

长期从事传染性疾病临床救治工作，能熟练完成以下疾病的诊治工作：慢性乙型、丙型病毒性肝炎、肝硬化、重症肝炎、肝衰竭、各种病因引起的肝损伤、艾滋病、伤寒、疟疾、流感、恙虫病、肝吸虫病等传染病与寄生虫病。

true 蔡正文主任医师

三级甲等广西医科大学第二附属医院

好评率：- 接诊量：- 平均响应：-

擅长恶性肿瘤疾病、血液肿瘤的诊断与治疗。尤其对恶性肿瘤的靶向治疗和免疫治疗，以及造血干细胞移植有较高的造诣，达到国内先进水平。

false 李敏副主任医师

三级甲等广西医科大学第二附属医院

好评率：100% 接诊量：1 平均响应：-

待补充

false 江永美主治医师

三级甲等广西医科大学第二附属医院

好评率：100% 接诊量：6 平均响应：-

女性情感问题，青少年情绪障碍及抑郁症、焦虑症等心理科常见问题的诊疗

false 叶小龙主治医师

三级甲等广西医科大学第二附属医院

好评率：100% 接诊量：71 平均响应：-

业务专长：带状疱疹后神经痛、骨关节疼痛、三叉神经痛、癌症疼痛的规范化治疗。

true 廖国林主治医师

三级甲等广西医科大学第二附属医院

好评率：100% 接诊量：206 平均响应：-

消化系统疾病，如胃食管疾病（胃炎、反流性食管炎）、肝病、肠道疾病、胆胰疾病（急性胰腺炎、胆石症）等

false 梁佳维主治医师

三级甲等广西医科大学第二附属医院

好评率：100% 接诊量：4 平均响应：-

脊柱疾病

true 刘文洲主治医师

三级甲等广西医科大学第二附属医院

好评率：- 接诊量：- 平均响应：-

熟悉对肺部良恶性肿瘤、食管疾病、纵隔肿瘤、胸部外伤、先天性心脏病、心脏瓣膜病、血管疾病等心胸外科疾病的诊治，熟悉胸外科及心脏外科各种微创手术治疗技术。

true 李郭乔主治医师

三级甲等广西医科大学第二附属医院

好评率：100% 接诊量：1 平均响应：-

甲状腺良性、恶性结节消融、甲亢消融，甲旁亢消融；甲状腺结节诊治、甲状腺结节穿刺活检术、甲状腺癌的筛检，其他甲状腺疾病诊治，其他如糖尿病等常见内分泌疾病诊治。

true 徐小龙主治医师

三级甲等广西医科大学第二附属医院

好评率：100% 接诊量：26 平均响应：15分钟

擅长泌尿系结石、肿瘤及前列腺疾病的微创手术治疗，尤其是小儿泌尿系疾病的诊断及治疗。

接诊医生：

2024-10-31 01:26:54

科普文章

催乳素分泌不足怎么办？

在临床上催乳素也称之为“泌乳素”，是人体分泌的重要激素，催乳素分泌不足在临床上比较常见，而催乳素分泌不足具体的原因可能是因为内分泌失调所导致，出现这种情况应该怎么办呢？大致有以下几个方面。

第一，如果是孕妇出现催乳素偏低，需要给予营养的补充，在平时的日常生活中保证营养均衡，保证微量元素、矿物质以及必需氨基酸的摄入，其中多吃一些含有蛋白质的食物，比如在平时的日常生活中可以吃鸡蛋、牛奶、豆制品等，同时也应该注意休息，避免劳累，不要过度的用脑，保持充足的睡眠，这些都是非常重要的，通过积极的调养，催乳素偏低的情况可以得到改善。

第二，垂体功能减退或垂体病变所导致的催乳素偏低，这时需要去医院进行详细的检，其中包括脑垂体的磁共振检查，一旦发现垂体瘤或者垂体增生以及垂体的其他病变，主要采取针对性的治疗，必要时需要进行外科手术治疗，临床上催乳素偏低可能会引起女性患者月经紊乱、月经先后期不定，严重者会导致不孕不育的发生。

总结，在临床上催乳素偏低，往往需要结合生活方式的注意、饮食的改善、劳逸结合综合进行。同时可以配合中医的方法进行治疗，比如应用鹿胎膏帮助缓解催乳素偏低，而垂体的问题导致催乳素偏低，根据情况可以选择外科手术治疗等。

病例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.

术前CT肿瘤轮廓不规则性预测肾细胞癌预后

以下内容来源于PubMed。

Summary

Background

Radiology-based prognostic biomarkers play a crucial role in patient counseling, enhancing surveillance, and designing clinical trials effectively. This study aims to assess the predictive significance of preoperative CT-based tumor contour irregularity in determining clinical outcomes among patients with renal cell carcinoma (RCC).

Methods

We conducted a retrospective multi-institutional review involving 2218 patients pathologically diagnosed with RCC. The training and internal validation sets included patients at Zhongshan Hospital between January 2009 and August 2019. The external test set comprised patients from the First Affiliated Hospital, Zhejiang University School of Medicine (January 2016 to January 2018), the Xiamen Branch of Zhongshan Hospital (November 2017 to June 2023), and the Cancer Imaging Archive. The contour irregularity degree (CID), quantified as the ratio of irregular cross-sections to the total tumor cross-sections, was analyzed for its prognostic relevance across different subgroups of RCC patients. A novel CID-based scoring system was developed, and its predictive efficacy was evaluated and compared with existing prognostic models.

Findings

The CID exhibited significant discriminatory power in predicting overall survival (OS), recurrence-free survival (RFS), and disease-specific survival (DSS) among patients with RCC tumors measuring 3 cm or larger (all p < 0.001). Multivariate analyses confirmed the CID as an independent prognostic indicator. Notably, the CID augmented prognostic stratification among RCC patients within distinct risk subgroups delineated by SSIGN models and ISUP grades. The CID-based nomogram (C-Model) demonstrated robust predictive performance, with C-index values of 0.88 (95%CI: 0.84–0.92) in the training set, 0.92 (95%CI: 0.88–0.98) in the internal validation set, and 0.86 (95%CI: 0.81–0.90) in the external test set, surpassing existing prognostic models.

Interpretation

Routine imaging-based assessment of the CID serves as an independent prognostic factor, offering incremental prognostic value to existing models in RCC patients with tumors measuring 3 cm or larger.

Funding

This study was funded by grants from National Natural Science Foundation of China; Shanghai Municipal Health Commission; China National Key R&D Program and Science and Technology Commission of Shanghai Municipality.