更新于：2024-04-01

Blood Coagulation Disorders

凝血障碍

更新于：2024-04-01

基本信息

别名

Abnormal;coagulation、Abnormality of the coagulation cascade、BLOOD COAGULATION DEFECT

+ [103]

简介

Hemorrhagic and thrombotic disorders that occur as a consequence of abnormalities in blood coagulation due to a variety of factors such as COAGULATION PROTEIN DISORDERS; BLOOD PLATELET DISORDERS; BLOOD PROTEIN DISORDERS or nutritional conditions.

关联

597

项与凝血障碍相关的药物

Trenonacog alfa

重组凝血因子9

靶点

factor IX

作用机制

factor IX刺激剂

在研机构

Medexus Pharma, Inc. [+1]

原研机构

Inspiration Biopharmaceuticals, Inc.

在研适应症

血友病B

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2024-03-26

Fidanacogene elaparvovec

靶点

factor IX

作用机制

凝血因子IX基因转移

在研机构

Pfizer Inc.

原研机构

The Children's Hospital of Philadelphia

在研适应症

血友病B

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

加拿大

首次获批日期2023-12-27

Iptacopan

盐酸伊普可泮

靶点

CFB

作用机制

CFB抑制剂

在研机构

Novartis Pharmaceuticals Corp. [+5]

原研机构

Novartis Pharma AG

在研适应症

阵发性睡眠性血红蛋白尿症 [+10]

非在研适应症

溶血 [+3]

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2023-12-05

3,928

项与凝血障碍相关的临床试验

NCT05583539 / Not yet recruitingN/AIIT

A Pilot Study of Thromboelastography Guided Blood Product Transfusion for Patient With Cirrhosis and Upper Gastrointestinal Bleeding

The goal of this clinical trial is to compare resuscitation strategies in patients with cirrhosis and gastrointestinal bleeding. The main question it aims to answer is whether thromboelastography guided resuscitation decreased the amount of fresh frozen plasma patients receive. Patients will receive blood products guided by thromboelastography in the intervention group. Researchers will compare the patients who undergo thromboelastography guided resuscitation to those who receive usual care to see which strategy leads to the use of less blood products, specifically less fresh frozen plasma.

开始日期2025-01-16

申办/合作机构

Vanderbilt University Medical Center

NCT05830916 / Not yet recruitingN/AIIT

Diagnostic Role of Antiphospholipid Antibodies and Microparticles in Immune Thrombocytopenic Patients With Thrombosis

Identify the procoagulant profile in immune thrombocytopenic patients with thrombosis.
Clinical implications of antiphospholipid antibodies in ITP patients with thrombosis.
Diagnostic role of microparticles in ITP patients with thrombosis.

开始日期2024-09-01

申办/合作机构

Assiut University

NCT04418414 / Not yet recruiting临床1期

ET3-201: Phase 1 Study of Hematopoietic Stem Cell Transplantation (HSCT) Gene Therapy Incorporating a Lentiviral Vector (LV) Encoding a High Expressing Factor VIII Transgene for Treatment of Severe Hemophilia A

This is a first-in-human, non-randomized, open label, single treatment, Phase 1 study in approximately 7 patients with severe hemophilia A. The study will evaluate gene therapy by transplantation of autologous CD34+ hematopoietic stem cells transduced ex vivo with the CD68-ET3 lentiviral vector.

开始日期2024-09-01

申办/合作机构

Expression Therapeutics LLC

100 项与凝血障碍相关的临床结果

登录后查看更多信息

100 项与凝血障碍相关的转化医学

登录后查看更多信息

0 项与凝血障碍相关的专利（医药）

登录后查看更多信息

128,639

项与凝血障碍相关的文献（医药）

2024-12-01·Platelets

Transcription factor 3 is dysregulated in megakaryocytes in myelofibrosis.

Article

作者: Ryan J Collinson ; Lynne Wilson ; Darren Boey ; Zi Yun Ng ; Bob Mirzai ; Hun S Chuah ; Rebecca Howman ; Carolyn S Grove ; Jacques A J Malherbe ; Michael F Leahy ; Matthew D Linden ; Kathryn A Fuller ; Wendy N Erber ; Belinda B Guo

Transcription factor 3 (TCF3) is a DNA transcription factor that modulates megakaryocyte development. Although abnormal TCF3 expression has been identified in a range of hematological malignancies, to date, it has not been investigated in myelofibrosis (MF). MF is a Philadelphia-negative myeloproliferative neoplasm (MPN) that can arise de novo or progress from essential thrombocythemia [ET] and polycythemia vera [PV] and where dysfunctional megakaryocytes have a role in driving the fibrotic progression. We aimed to examine whether TCF3 is dysregulated in megakaryocytes in MPN, and specifically in MF. We first assessed TCF3 protein expression in megakaryocytes using an immunohistochemical approach analyses and showed that TCF3 was reduced in MF compared with ET and PV. Further, the TCF3-negative megakaryocytes were primarily located near trabecular bone and had the typical "MF-like" morphology as described by the WHO. Genomic analysis of isolated megakaryocytes showed three mutations, all predicted to result in a loss of function, in patients with MF; none were seen in megakaryocytes isolated from ET or PV marrow samples. We then progressed to transcriptomic sequencing of platelets which showed loss of TCF3 in MF. These proteomic, genomic and transcriptomic analyses appear to indicate that TCF3 is downregulated in megakaryocytes in MF. This infers aberrations in megakaryopoiesis occur in this progressive phase of MPN. Further exploration of this pathway could provide insights into TCF3 and the evolution of fibrosis and potentially lead to new preventative therapeutic targets.

2024-12-01·Hematology (Amsterdam, Netherlands)

Real-world long-term safety and effectiveness of turoctocog alfa in the treatment of haemophilia A in Japan: results from a multicentre, non-interventional, post-marketing study.

Article

作者: Azusa Nagao ; Ayumi Deguchi ; Keiji Nogami

OBJECTIVES:

To assess the safety and effectiveness of turoctocog alfa in previously treated patients (PTPs) and previously untreated patients (PUPs) with haemophilia A in a real-world setting in Japan.

METHODS:

This multicentre, non-interventional, post-marketing study recruited patients with haemophilia A who initiated treatment with turoctocog alfa from 18 sites (08/2014-12/2018). The primary endpoint was adverse events (AEs) during the 2-year study period.

RESULTS:

The safety and effectiveness analysis set included 39 patients. In total, 13 (33.3%) patients reported ≥1 AE; incidence rate was 60.4 events/100 patient-years of exposure (PYE). Treatment was withdrawn in two cases: pruritus in a PTP and factor VIII inhibitor development in a PUP. Inhibitor development occurred in 2.6% of all patients, with an incidence rate of 3.8 events/100 PYE. The rate of inhibitor development was 0%, 25% and 20% in PTPs, PUPs and PUPs with severe type, respectively. The haemostatic success rate was 91.4% for 383 bleeding episodes and 85.7% for 14 surgeries. The negative binomial annualised bleeding rate for the prophylaxis regimen was 6.19 episodes/year (95% CI, 3.69-10.38). The mean (SD) total consumption of turoctocog alfa (n = 34; excluding FVIII inhibitors) was 5,382.6 (7,180.1) IU/kg/year/patient; consumption was 4,133.1 (1,452.4) IU/kg/year/patient for prophylaxis.

DISCUSSION:

The effectiveness and safety profiles were comparable to those observed in other turoctocog alfa trials; effectiveness analysis and consumption were not affected by treatment regimens.

CONCLUSION:

Long-term use of turoctocog alfa therapy in clinical practice posed no newly identified safety issues and was effective for prophylaxis and treatment of bleeds in patients with haemophilia A in Japan.

2024-12-01·Platelets

Development of a super-hydrophilic anaerobic tube for the optimization of platelet-rich fibrin.

Article

作者: Yan Wei ; Yihong Cheng ; Hongjiang Wei ; Yulan Wang ; Xiaoxin Zhang ; Richard J Miron ; Yufeng Zhang ; Shanglan Qing

Horizontal platelet-rich fibrin (H-PRF) contains a variety of bioactive growth factors and cytokines that play a key role in the process of tissue healing and regeneration. The blood collection tubes used to produce Solid-PRF (plasmatrix (PM) tubes) have previously been shown to have a great impact on the morphology, strength and composition of the final H-PRF clot. Therefore, modification to PM tubes is an important step toward the future optimization of PRF. To this end, we innovatively modified the inner wall surface of the PM tubes with plasma and adjusted the gas environment inside the PM tubes to prepare super-hydrophilic anaerobic plasmatrix tubes (SHAP tubes). It was made anaerobic for the preparation of H-PRF with the aim of improving mechanical strength and bioactivity. The findings demonstrated that an anaerobic environment stimulated platelet activation within the PRF tubes. After compression, the prepared H-PRF membrane formed a fibrous cross-linked network with high fracture strength, ideal degradation characteristics, in addition to a significant increase in size. Thereafter, the H-PRF membranes prepared by the SHAP tubes significantly promoted collagen synthesis of gingival fibroblast and the mineralization of osteoblasts while maintaining excellent biocompatibility, and advantageous antibacterial properties. In conclusion, the newly modified PRF tubes had better platelet activation properties leading to better mechanical strength, a longer degradation period, and better regenerative properties in oral cell types including gingival fibroblast and alveolar osteoblasts. It also improves the success rate of H-PRF preparation in patients with coagulation dysfunction and expands the clinical application scenario.

3,636

项与凝血障碍相关的新闻（医药）

2024-03-31

·米内网

千亿市场再掀热浪！9款罕见病新药上市可期，华东、诺华蓄势待发，42个品种“解锁”新用法

精彩内容罕见病“用药短缺”备受关注。近年来国家频频出台利好政策，以推动罕见病新药研发及市场准入。据不完全统计，2024年以来，至少有5款罕见病新药登场亮相，涵盖血液、皮肤、消化系统等治疗领域；9款新品有望于年内获批，涉及华东、诺华等知名药企。临床用药需求的激增，催生超说明书用药的规范化和普遍化，42个罕见血液病治疗药“解锁”新用法，人免疫球蛋白注射剂、利妥昔单抗注射剂等多款2022年在中国三大终端六大市场（统计范围见文末）销售额超30亿元的重磅品种在列。激励政策层出不穷，千亿罕见病药市场再起波澜“无药可用”是大多数罕见病患者的常态。据统计，目前全球共发现7000多种罕见病，有药可治的比例不足10%。我国有2000多万罕见病患者，每年新增患者超20万。确诊难、治疗方法少、可用药品少等难题交织，让罕见病群体身陷困境。近年来，随着罕见病药进保提速，罕见病目录相继发布，驱动罕见病新药研发及市场准入的利好政策陆续出台，叠加罕见病领域未被满足的需求大、市场竞争小等特点，越来越多企业加码布局罕见病药物的研发。一些“无药可治”的罕见病患者，或能在与时间的生死赛跑中等来“救命良药”。近年来国家发布的部分鼓励罕见病药研发和生产的相关政策来源：国家卫健委、国家药监局等，米内网整理《2023年度药品审评报告》显示，2023年国家药监局共批准45个罕见病药（不含化药4类罕见病药），获批产品涵盖血液、神经、代谢、免疫、罕见肿瘤等多个治疗领域，填补了我国多个罕见病的临床用药空白。如2023年4月获批上市的硫酸氢司美替尼胶囊，成为首个获批的Ⅰ型神经纤维瘤病（NF1）相关丛状神经纤维瘤（PN）治疗药；同年6月获批上市的卡谷氨酸分散片，用于N-乙酰谷氨酸合成酶缺乏症（NAGSD）、丙酸血症（PA）等引起的高氨血症，是我国首个获批用于该类疾病的治疗药物。从审评审批路径上看，共有15个品种通过优先审评审批程序得以加快上市，其中纳鲁索拜单抗注射液为石药集团的1类创新药，是全球首个IgG4 RANKL抑制剂，用于治疗不可手术切除或手术切除可能导致严重功能障碍的骨巨细胞瘤。与原有治疗药（地舒单抗）开展头对头研究显示，纳鲁索拜单抗具有显著临床优势，米内网数据显示，2022年在中国三大终端六大市场地舒单抗合计销售额超过8亿元，同比增长110.94%。2023年通过优先审评审批程序获批的罕见病药来源：国家药监局官网，米内网整理伴随临床用药需求的推动，以及激励创新研发政策的出台，罕见病药物市场持续升温。有业内专业机构指出，中国罕见病药市场于2016年及2020年分别占全球罕见病市场的0.4%及1%，预计2030年将激增至259亿美元，约合1872亿元（按实时汇率换算），市场潜力十足。9款罕见病新药上市可期，华东、诺华......蓄势待发据不完全统计，今年以来已有5款罕见病新药获批上市，包括C5抑制剂可伐利单抗注射液、铜吸收抑制剂醋酸锌片、GLP-2类似物替度格鲁肽、重组猪FⅧ（rpFⅧ）药物注射用舒索凝血素α和IL-36R抑制剂佩索利单抗注射液。这些产品的到来，将为阵发性睡眠性血红蛋白尿症、肝豆状核变性、短肠综合征、获得性血友病A、泛发性脓疱型银屑病等罕见病患者带来了新的治疗选择。展望2024年，还有哪些备受关注的罕见病新药在国内登场亮相，惠及更多患者？笔者结合公开资料及CDE优先审评公示信息，筛选出9款有望于今年获批上市的罕见病新药，以供大家参考。2024年有望获批的罕见病新药来源：米内网中国申报进度（MED）数据库注射用利纳西普由华东医药与Kiniksa Pharmaceuticals合作研发，是一款IL-1免疫抑制剂。米内网数据显示，2022年中国三大终端六大市场免疫抑制剂市场规模超过280亿元，2023年上半年突破155亿元，全年销售额有望再创新高。近年来中国三大终端六大市场免疫抑制剂销售趋势（单位：万元）来源：米内网格局数据库CDE官网显示，2023年1月和12月，该药相继被CDE纳入优先审评，分别针对成人和12岁及以上青少年冷吡啉相关周期性综合征（CAPS）、成人和12岁及以上青少年复发性心包炎（RP）。目前，国内暂无用于冷吡啉相关周期性综合征，以及复发性心包炎的有效治疗药物。2018年11月，注射用利纳西普被纳入CDE发布的《临床急需境外新药名单（第一批）》；2023年9月，CAPS及复发性心包炎均被收录于国家卫健委发布的《第二批罕见病目录》。盐酸伊普可泮胶囊是诺华研发的一款靶向补体旁路途径B因子的口服抑制剂。2023年6月，该药的上市申请被CDE纳入优先审评，用于治疗成人阵发性睡眠性血红蛋白尿症（PNH）患者。靶向抑制补体C5是PNH的标准疗法，米内网数据显示，目前全球仅有2款针对PNH治疗的C5抑制剂获批上市，其中阿斯利康的依库珠单抗已在国内获批。现有的C5抑制剂以输注的方式给药，且可能无法控制PNH症状，部分患者在接受抗C5治疗后仍有残存贫血和依赖输血。而盐酸伊普可泮胶囊是一种B因子抑制剂，B因子驱动了PNH中补体介导的溶血。该药通过作用免疫系统的补体旁路途径中的近端通路，可全面控制血管内外的红细胞破坏（血管内和血管外溶血）。该药已于2023年12月获FDA批准，作为口服单药疗法治疗成人PNH。盐酸伊普可泮胶囊项目进度来源：米内网项目进度数据库注射用Vonicog alfa是武田研发的一款重组血管性血友病因子。2023年1月，该产品的上市申请被CDE纳入优先审评，适应症为成人血管性血友病（VWD）患者，包括按需治疗和出血事件的控制，以及围手术期出血管理。血管性血友病为常见的遗传性出血性疾病之一，是因血管性血友病因子（VWF）基因突变引起血浆中的血管性血友病因子数量减少或质量异常所引起的疾病。注射用Vonicog alfa包含完整的VWF多聚体，含有超大多聚体（ULMs），半衰期长，可有效实现血管性血友病的替代治疗，并为患者提供个性化的出血控制方法。据悉，该药是全球首个且唯一一个重组血管性血友病因子产品，目前已在美国、欧盟、加拿大、瑞士、澳大利亚和日本等地获得上市许可，用于18岁及以上血管性血友病患者的按需治疗和出血事件控制，以及围手术期出血管理。注射用Vonicog alfa全球获批及申报上市情况来源：米内网全球药物研发数据库42个品种“解锁”新用法，多款超30亿重磅产品在列除了加快罕见病药上市步伐，针对罕见病用药可及性低等问题，广东省药学会于近日发布了《血液系统罕见病超药品说明书用药专家共识（2024版）》（下文简称《共识》），有望进一步提高部分罕见血液病获得治疗的可能性。来源：广东省药学会官网据梳理，《共识》由广东省药学会罕见病专家委员会组织编写，从12种血液系统罕见病共42种治疗药物遴选出62条用药方案凝结而成。从超说明书内容上看，新增针对血友病及其相关疾病治疗的用药信息最多，合计11条；用于朗格汉斯细胞组织细胞增生症（8条）、原发性轻链型淀粉样变（8条）、Castleman综合症（7条）、Erdheim-Chester病（7条）、湿疹-血小板减少-免疫缺陷综合征（7条）等位居其后。具体产品情况方面，超说明书适应症达3项及以上的品种有5个，分别为泼尼松片剂、环磷酰胺注射剂/片剂、环孢素注射剂/胶囊剂/溶液剂、沙利度胺片剂以及硼替佐米注射剂。从治疗亚类上看，抗肿瘤药为主力，占据14个席位；免疫抑制剂、止血药分别占9个和8个，免疫刺激剂和全身用皮质激素类则各占2个。罕见病药超说明书用药专家共识（血液系统-2024版）来源：广东省药学会官网，米内网整理环孢素是由11个氨基酸残基组成的环状多肽药物，主要用于器官移植后的免疫抑制、银屑病、肾病综合征等。在中国公立医疗机构终端，该品种2022年销售额超过20亿元，2023年上半年同比增长7.01%，中美华东制药、诺华、兴齐眼药市占比均达两位数。在本版《共识》中，环孢素新增了3项超说明书适应症，包括获得性血友病免疫抑制治疗、Castleman综合症及朗格汉斯细胞组织细胞增生症，将为罕见血液病患者提供了新的用药选择。2023年上半年中国公立医疗机构终端环孢素品牌格局来源：米内网中国公立医疗机构药品终端竞争格局硼替佐米是双肽基硼酸盐类似物，是全球首款人工合成的新型蛋白酶体竞争性抑制剂，主要用于多发性骨髓瘤和套细胞淋巴瘤的治疗。受国采影响，该品种在中国公立医疗机构终端销售额逐年下滑，从2020年的超17亿元跌至2022年的约6亿元。在本版《共识》中，硼替佐米被允许超说明书用于血液疾病治疗领域，涉及Castleman综合症、POEMS综合征、原发性轻链型淀粉样变等，有望拉动其销售市场的复苏。42个纳入本版《共识》的品种中，还包括人免疫球蛋白注射剂、利妥昔单抗注射剂、重组血小板生成素注射剂、吗替麦考酚酯注射剂/片剂/胶囊剂等2022年在中国三大终端六大市场销售规模超30亿元的重磅药，产品潜力有望进一步释放。来源：米内网数据库、国家药监局等注：米内网《中国三大终端六大市场药品竞争格局》，统计范围是：城市公立医院和县级公立医院、城市社区中心和乡镇卫生院、城市实体药店和网上药店，不含民营医院、私人诊所、村卫生室，不含县乡村药店；上述销售额以产品在终端的平均零售价计算。数据统计截至3月29日，如有疏漏，欢迎指正！本文为原创稿件，转载请注明来源和作者，否则将追究侵权责任。投稿及报料请发邮件到872470254@qq.com稿件要求详询米内微信首页菜单栏商务及内容合作可联系QQ：412539092【分享、点赞、在看】点一点不失联哦

上市批准优先审批申请上市免疫疗法

2024-03-29

·梅斯医学

手足口病即将到达感染高峰期，快来收藏这份诊疗指南

随着气温升高，手足口病即将进入高发季节。手足口病是由多种肠道病毒引起的5岁及以下儿童常见急性传染性疾病，4-7月为手足口病春夏季感染高峰。病原学肠道病毒属于小RNA病毒科肠道病毒属。手足口病（HFMD）由肠道病毒引起，主要致病血清型包括柯萨奇病毒(Coxsackievirus，CV)A组4～7、9、10、16型和B组1～3、5型，埃可病毒(Echovirus)的部分血清型和肠道病毒71型(Enterovirus A71，EV-A71)等，其中以CV-A16和EV-A71最为常见，其中EV-A71具有致病性强、传染性高、嗜神经等特点,可致严重甚至致命的神经系统及心肺并发症，重症及死亡病例多由EV-A71所致。流行病学1、常见亚型：亚基因型EV-A71_C4、CVA16_B1b、CVA6_D3a、CVA10_ F目前在中国占主导地位。2、传染源：患儿和隐性感染者，可通过感染者的粪便、咽喉分泌物、唾液和疱疹液等广泛传播。3、传播途径：密切接触，通过接触被病毒污染的手、毛巾、手绢、牙杯、玩具、食具、奶具以及床上用品、内衣等引起感染；呼吸道飞沫传播；饮用或食入被病毒污染的水和食物。4、易感人群：婴幼儿和儿童普遍易感，以5岁以下儿童为主。5、好发季节：该病全年都可以发病，在北方地区夏秋高发，但有逐渐提早的趋势。在南方地区以春夏为主高峰，秋冬季节为次高峰。临床表现1、潜伏期：多为2～10 d，平均3～5 d。2、出疹期：主要表现为发热，手、足、口、臀等部位出疹，可伴有咳嗽、流涕、食欲不振等症状。典型皮疹表现为斑丘疹、丘疹、疱疹。皮疹周围有炎性红晕，疱疹内液体较少，不疼不痒，皮疹恢复时不结痂、不留疤。不典型皮疹通常小、厚、硬、少，有时可见瘀点、瘀斑。某些型别肠道病毒如CV-A6和CV-A10所致皮损严重，皮疹可表现为大疱样改变，伴疼痛及痒感，且不限于手、足、口部位。此期属于手足口病普通型，绝大多数在此期痊愈。3、神经系统受累期：少数病例可出现中枢神经系统损害，多发生在病程1～5 d，表现为精神差、嗜睡、吸吮无力、易惊、头痛、呕吐、烦躁、肢体抖动、肌无力、颈项强直等。此期属于手足口病重症病例重型，大多数可痊愈。4、心肺功能衰竭前期：多发生在病程5 d内，表现为心率和呼吸增快、出冷汗、四肢末梢发凉、皮肤发花、血压升高。此期属于手足口病重症病例危重型。及时识别并正确治疗，是降低病死率的关键。5、心肺功能衰竭期：可在心肺功能衰竭前期的基础上迅速进入该期。临床表现为心动过速(个别患儿心动过缓)、呼吸急促、口唇紫绀、咳粉红色泡沫痰或血性液体、血压降低或休克。亦有病例以严重脑功能衰竭为主要表现，临床可见抽搐、严重意识障碍等。此期属于手足口病重症危重型，病死率较高。6、恢复期：此期体温逐渐恢复正常，对血管活性药物的依赖逐渐减少，神经系统受累症状和心肺功能逐渐恢复，少数可遗留神经系统后遗症。部分手足口病例(多见于CV-A6、CV-A10感染者)在病后2～4周有脱甲的症状，新甲于1～2月长出。辅助检查1、实验室检查（1）血常规及C-反应蛋白(CRP)多数病例白细胞计数正常，部分病例白细胞计数、中性粒细胞比例及CRP可升高。（2）病原学及血清学临床样本（咽拭子、粪便或肛拭子、血液等标本）肠道病毒特异性核酸检测阳性或分离到肠道病毒。急性期血清相关病毒IgM抗体阳性。恢复期血清CV-A16、EV-A71或其他可引起手足口病的肠道病毒中和抗体比急性期有4倍及以上升高。（3）血生化部分病例丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、肌酸激酶同工酶（CK-MB）轻度升高，病情危重者肌钙蛋白、血糖、乳酸升高。（4）脑脊液神经系统受累时，脑脊液符合病毒性脑膜炎和/或脑炎改变，表现为外观清亮，压力增高，白细胞计数增多，以单核细胞为主（早期以多核细胞升高为主），蛋白正常或轻度增多，糖和氯化物正常。2、影像学检查（1）影像学：轻症患儿肺部无明显异常。重症及危重症患儿并发神经源性肺水肿时，两肺野透亮度减低，磨玻璃样改变，局限或广泛分布的斑片状、大片状阴影，进展迅速。（2）颅脑CT和/或MRI颅脑CT检查可用于鉴别颅内出血、脑疝、颅内占位等病变。神经系统受累者MRI检查可出现异常改变，合并脑干脑炎者可表现为脑桥、延髓及中脑的斑点状或斑片状长T1长T2信号。并发急性弛缓性麻痹者可显示受累节段脊髓前角区的斑点状对称或不对称的长T1长T2信号。（3）心电图可见窦性心动过速或过缓，Q-T间期延长，ST-T改变。（4）脑电图神经系统受累者可表现为弥漫性慢波，少数可出现棘(尖)慢波。（5）超声心动图重症患儿可出现心肌收缩和/或舒张功能减低，节段性室壁运动异常，射血分数降低等。诊断标准在临床诊断病例基础上，具有下列之一者即可确诊。1、肠道病毒（CV-A16、EV-A71等）特异性核酸检查阳性。2、分离出肠道病毒，并鉴定为CV-A16、EV-A71或其他可引起手足口病的肠道病毒。3、急性期血清相关病毒IgM抗体阳性。4、恢复期血清相关肠道病毒的中和抗体比急性期有4倍及以上升高。重症病例的早期识别重症病例诊疗关键在于及时准确地识别第2期和第3期，阻止发展为第4期。年龄3岁以下、病程3天以内和EV-A71感染为重症高危因素，下列指标提示患儿可能发展为重症病例危重型：1、持续高热：体温大于39℃，常规退热效果不佳；2、神经系统表现：出现精神萎靡、头痛、眼球震颤或上翻、呕吐、易惊、肢体抖动、吸吮无力、站立或坐立不稳等；3、呼吸异常：呼吸增快、减慢或节律不整，安静状态下呼吸频率超过30～40次/分；4、循环功能障碍：心率增快（＞160次/分）、出冷汗、四肢末梢发凉、皮肤发花、血压升高、毛细血管再充盈时间延长（＞2秒）5、外周血白细胞计数升高：外周血白细胞计数≥15×109/L，除外其他感染因素；6、血糖升高：出现应激性高血糖，血糖＞8.3mmol/L；7、血乳酸升高：出现循环功能障碍时，通常血乳酸≥2.0mmol/L，其升高程度可作为判断预后的参考指标。治疗目前尚无特效抗肠道病毒药物，手足口病的治疗仍以对症支持治疗为主。研究显示，干扰素α喷雾或雾化、利巴韦林静脉滴注早期使用可有一定疗效，若使用利巴韦林应关注其不良反应和生殖毒性。不应使用阿昔洛韦、更昔洛韦、单磷酸阿糖腺苷等药物治疗。1、一般治疗注意隔离，避免交叉感染；清淡饮食；做好口腔和皮肤护理。积极控制高热，体温超过38.5℃者，采用物理降温（温水擦浴、使用退热贴等）或应用退热药物治疗。惊厥病例需要及时止惊2、液体疗法重症病例可出现脑水肿、肺水肿及心功能衰竭，应控制液体入量，给予生理需要量60～80ml/（kg·d）（脱水剂不计算在内），建议匀速给予，即2.5～3.3ml/（kg·h），注意维持血压稳定。休克病例在应用血管活性药物同时，给予生理盐水5～10ml/（kg·次）进行液体复苏，15～30分钟内输入，此后酌情补液，避免短期内大量扩容。仍不能纠正者给予胶体液（如白蛋白或血浆）输注。有条件的医疗机构可依据中心静脉压（CVP）、动脉血压（ABP）等指导补液。3、降颅压常用甘露醇，严重颅内高压或低钠血症患儿可考虑联合使用高渗盐水（3%氯化钠）。有心功能障碍者，可使用利尿剂，如呋塞米1～2mg/kg静脉注射。4、血管活性药物心肺功能衰竭前期患儿血流动力学改变为高动力高阻力型，以使用扩血管药物为主。心肺功能衰竭期血压下降时，可应用正性肌力及升压药物治疗。5、静脉丙种球蛋白有脑脊髓炎和持续高热等表现者以及危重病例可酌情使用，剂量1.0g/（kg·d），连用2天。6、糖皮质激素有脑脊髓炎和持续高热等表现者以及危重病例酌情使用。7、机械通气（1）机械通气指征：出现以下表现之一者，可予气管插管机械通气：①呼吸急促、减慢或节律改变；②气道分泌物呈淡红色或血性；③短期内肺部出现湿性啰音；④胸部X线检查提示肺部明显渗出性病变；⑤脉搏血氧饱和度（SpO2）或动脉血氧分压（PaO2）下降；⑥面色苍白、紫绀、皮温低、皮肤发花、血压下降；⑦频繁抽搐或昏迷。（2）撤机指征①自主呼吸恢复正常，咳嗽反射良好；②氧合指数（PaO2/FiO2）≥200mmHg，PEEP＜10cmH2O时，开始做撤机评估；③血气分析好转，胸片肺部渗出与肺水肿好转；④意识状态好转；⑤循环稳定。预防1、一般预防措施保持良好的个人卫生习惯。勤洗手，不要让儿童喝生水，吃生冷食物。儿童玩具和常接触到的物品应当定期进行清洁消毒。避免儿童与患手足口病儿童密切接触。2、接种疫苗EV-A71型灭活疫苗可用于6月龄～5岁儿童预防EV-A71感染所致的手足口病，基础免疫程序为2剂次，间隔1个月，鼓励在12月龄前完成接种。撰文 | 梅斯医学编辑 | Swagpp● 震惊！大三甲医生惨痛教训：35岁住院医，工作6年，跟风读研后反而找不到工作了！网友：为读研而读研你太傻！学历贬值你不懂?● 柳叶刀最新：全球生育率持续下降，逼近临界值！25年后，近50%国家的自然增长率为负，中国人口将持续减少● 重磅！！国家卫健委：2024年将推进“先诊疗后付费”等新模式！依靠信用，“花呗”版看病真的来了！意味着什么？版权说明：梅斯医学（MedSci）是国内领先的医学科研与学术服务平台，致力于医疗质量的改进，为临床实践提供智慧、精准的决策支持，让医生与患者受益。欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。点击下方「阅读原文」立刻下载梅斯医学APP！

临床2期临床结果

2024-03-29

·FierceBiotech

Chutes & Ladders—Ex-Biogen leader John Cox continues biotech CEO run, taking Dyne job

None Welcome to this week's Chutes & Ladders, our roundup of hirings, firings and retirings throughout the industry. Please send the good word—or the bad—from your shop to Max Bayer or Gabrielle Masson, and we will feature it here at the end of each week. Former longtime Biogen exec John Cox continues biotech run, tapped as new Dyne CEO Dyne Therapeutics John Cox cut his teeth at Biogen, where over nearly 14 years he ascended from the director of manufacturing sciences to the executive vice president of global commercial and technical operations. Most of his final year was spent orchestrating the spinoff of the company’s hemophilia business into a standalone biotech, Bioverativ. Despite that company getting acquired by Sanofi, Cox’s career was catapulted into its second chapter as a perennial biotech CEO. Dyne Therapeutics has taken notice, hiring Cox as its new CEO. Current CEO Joshua Brumm is stepping down to pursue jobs in healthcare investing, the company said in its announcement. Following Bioverativ, Cox was CEO of Flagship biotech Torque Therapeutics before helming Repertoire Immune Medicines, a merger of Torque and Cogen Immune Medicines. He left Repertoire in November 2022, holding a couple of board positions since. Release Madrigal’s former US sales leader joins Nuvation as CCO Nuvation Bio A few months before Mirati’s KRAS inhibitor was approved, VP of U.S. sales Colleen Sjogren left for a similar role at Madrigal. A few months before Madrigal won FDA approval for the first MASH treatment, Sjogren bolted as part of a larger leadership overhaul. Now, the veteran commercial executive is back, called on to lead the commercial unit at Nuvation Bio, which itself is expected to have a licensed product in less than two years. It’s a critical hire for the company, with Sjogren sporting one of the most consistent track records in recent years. Prior to her gigs at Mirati and Madrigal, she was VP of the national cell therapy team at Gilead’s Kite, one of the most successful wings of the company. Nuvation is advancing its own oncology pipeline, led by two clinical-stage solid tumor meds, NUV-868 and NUV-1511. The former is slightly in the lead and preparing to launch into a phase 2 trial, with Nuvation CEO David Hung, M.D., saying in a release that the company is working to become commercial stage by the end of 2025. Release The revolving door between biopharma and federal health agencies sweeps up 35-year vet Calico When Michael Lenardo, M.D., joined the National Institutes of Health's (NIH's) National Institute for Allergy and Infectious Diseases (NIAID), director Anthony Fauci, M.D., was just five years into the job. The latter legend left in 2022 after working through the toughest days of the pandemic and completing a directorial stint that spanned numerous presidents of both major parties. Leonardo is now heading for the exits himself, taking a gig in the biopharma industry as chief scientific officer at Calico. The biotech was founded by Google parent company Alphabet and is working on age-related diseases. Leonardo is co-director of NIAID’s clinical genomics program and also chief of the institute’s molecular development of the immune system team. The NIH division credits him with founding or co-founding numerous joint ventures with well-known research institutions and scholar programs. He'll join Calico in August once his NIAID term ends. Release > George Eliades, Ph.D., has ended a three-year stint at Jazz Pharmaceuticals, traversing over to Mythic Therapeutics to helm the ADC-focused biotech. Before joining Mythic as president and CEO, Eliades was Jazz’s SVP of corporate development and chief transformation officer. Release > Caribou Biosciences’ former chief medical officer Syed Rizvi, M.D., is switching CAR-T teams, heading over to serve as Poseida Therapeutics’ CMO starting April 1. Rizvi has clocked in extensive experience in the industry, holding leadership roles at Chimeric Therapeutics, Legend Biotech, Celgene, Novartis and Merck. Release > Ardelyx has hired Mike Kelliher to serve as the company’s EVP of corporate development and strategy. Before Ardelyx, Kelliher served as Horizon’s group VP of M&A and business development before the company’s $27.8 billion Amgen buyout. Release > Paris-based Egle Therapeutics is adding two new members to the team, bringing on Monica Gostissa, Ph.D., to serve as chief scientific officer and Reno Winter, Ph.D., as chief technical officer. Gostissa most recently served as VP of preclinical sciences for Jounce Therapeutics, while Winter is a biochemist that joined Egle in 2023 to help with manufacturing and supply strategy. Release > As Replimune revs up for a potential market approval, the company is remixing its leadership team, with Chief Strategy Officer Sushil Patel, Ph.D., set to succeed CEO Philip Astley-Sparke on April 1. Furthermore, Robert Coffin, Ph.D., co-founder, president and chief R&D officer, will move to an advisory role as Paul Bullock steps on as chief manufacturing officer after the retirement of co-founder and Chief Operations Officer Colin Love, Ph.D. Meanwhile, Chief Business Officer Pamela Esposito, Ph.D., and Chief Development Operations Officer Tanya Lewis are departing from their executive positions. Release > Precision therapy company IDRx has chosen David Kerstein, M.D., to serve as chief medical officer. Kerstein joins from Theseus Pharmaceuticals, where he held the same title, and has experience working across Anchiano Therapeutics, Takeda and Boston Biomedical. Release > Rocket Pharmaceuticals is revamping its leadership team, welcoming former Mirati (acquired by Bristol Myers Squibb) CFO Aaron Ondrey to lead Rocket’s financial team. Other changes include current Chief Operating Officer Kinnari Patel tacking on the role of president, head of R&D to her title, while Chief Medical Officer Jonathan Schwartz, M.D., has been appointed chief medical and gene therapy officer. Mark White, also listed as chief medical officer at Rocket on LinkedIn, has now been appointed general manager of commercial affairs, while previous general counsel and Chief Compliance Officer Martin Wilson will now serve as general counsel and chief corporate officer. Release > Synthego CEO Paul Dabrowski has stepped down, with Craig Christianson taking the helm as the company zooms its focus into therapeutic applications of CRISPR. New leader Christianson has been chosen after an “extensive search process” and joins the company from Water Street Healthcare Partners. Release > TransCode Therapeutics has tapped Daniel Vlock, M.D., to serve as the Boston-based biotech’s chief medical officer. The medical oncologist has served as Alopexx Pharmaceuticals' CMO and also led Alopexx Enterprises as CEO for more than 18 years. Release