Annals for Educators - 16 January 2018.,Annals of Internal Medicine

当前位置： X-MOL 学术 › Ann. Intern. Med. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Annals for Educators - 16 January 2018.
Annals of Internal Medicine ( IF 19.6 ) Pub Date : 2018-01-16 , DOI: 10.7326/afed201801160
Darren B. Taichman

Clinical Practice Points

Use of Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Autoimmune Disease. A Systematic Review

This systematic review describes adverse events in patients with cancer and concomitant autoimmune disease who received cancer immunotherapy with checkpoint inhibitors (CPIs).

Use this review to:

Start a teaching session with a multiple-choice question. We've provided one below!
Ask your learners what CPIs are. How do they work as antitumor agents? For what types of cancer have they been shown to be successful? Invite an oncologist to join your discussion.
Why have patients with autoimmune disease been excluded from clinical trials of CPIs? Why might the mechanism of action of CPIs lead to autoimmune adverse events?
Review the results of this study. What are the limitations of the available data? Use the authors' discussion and the accompanying editorial to help answer this question.
How are the observational reports identified in this review helpful for clinical practice and further research, despite their weaknesses?

Comparison of Five Major Guidelines for Statin Use in Primary Prevention in a Contemporary General Population

Five professional organizations in Europe and North America have published guidelines for using statins to prevent atherosclerotic cardiovascular disease. Application of the different guidelines to a single population aged 40 to 75 years would result in as few as 15% or as many as 44% of participants receiving statins. This study estimated how many cardiovascular events would be prevented using each guideline.

Use this paper to:

Ask your learners how they decide which patients should use statins for primary prevention of cardiovascular disease.
What do the guidelines recommend? Which ones do your learners know about?
Review Table 1, which summarizes the approaches taken by each of the 5 major guidelines. What are the key differences?
Ask your learners why following each of the guidelines results in a different number of patients recommended for statin use in the population modeled here and why the number of cardiovascular events differs.
Why do guideline groups issue different recommendations despite using largely the same evidence? Use the accompanying editorial to help frame your discussion.
What approach do your learners intend to follow? Why? What are the risks and benefits of their planned approaches?

Comparative Effectiveness of Implementation Strategies for Blood Pressure Control in Hypertensive Patients. A Systematic Review and Meta-analysis

This meta-analysis of data from 100 trials examines the comparative effectiveness of 8 implementation strategies for blood pressure control in adults with hypertension.

Use this review to:

Ask your learners what strategies are used in their practices to help patients reach blood pressure treatment goals.
Review the list of implementation strategies in Table 1. Which ones are used at your center? Before reviewing this study's results, ask your learners how well they think each of the listed strategies performs.
Review the results. Are your learners surprised?
Why do your learners think certain strategies work better than others?
If team-based approaches to blood pressure control are used at your institution's outpatient practices, who is involved? Who monitors performance in your practice? How is performance assessed? Invite a quality improvement officer to join your discussion.
Why do your learners think that involvement of nonphysician team members was found to be useful? What are the potential benefits, as well as barriers to their involvement? Use the accompanying editorial to help frame your discussion.
Log on and answer the accompanying questions to earn CME/MOC credit for yourself!

Diagnosis of Venous Thromboembolism: 20 Years of Progress

This special article details state-of-the-art algorithms for diagnosing deep venous thrombosis (DVT) and pulmonary embolism (PE) in adults, including pregnant women.

Use this paper to:

Ask your learners why establishing a pretest clinical probability of either DVT or PE is important. How does the pretest probability affect the choice of test and the interpretation of results?
How do your learners assess pretest probability? Do they do so in a systematic manner?
What is the PERC tool, and when is it useful?
Review the algorithms for evaluation of potential DVT and PE. Are these the approaches followed by your learners? Why or why not?
What imaging tests should be used for suspected DVT or PE in a pregnant patient? Does a V/Q or CT angiographic study expose the patient or fetus to more radiation?

Getting Credit for What You Do

By simply logging on when you click through to see the papers highlighted in this alert, you'll be eligible to claim point-of-care CME and MOC points. Logging on at the top right of the Web site takes seconds. Papers you look at when logged in will be recorded, allowing you to claim CME/MOC credit later by answering 2 simple questions about how you used the content. Give yourself the credit you deserve!

MKSAP 17 Question

A 55-year-old woman is evaluated in the emergency department for a 3-day history of diarrhea. She reports seven to eight stools daily without vomiting. She also notes abdominal cramping without vomiting and has been able to maintain adequate fluid intake. Medical history is significant for metastatic malignant melanoma, for which she recently completed the third of four planned doses of ipilimumab therapy. She has no history of inflammatory bowel disease, recent antibiotic use, recent travel, or consumption of uncooked foods. The remainder of the medical history is noncontributory, and she takes no other medications.

On physical examination, temperature is 37.5 °C (99.5 °F), blood pressure is 125/85 mm Hg, pulse rate is 90/min without orthostatic changes, and respiration rate is 14/min. The abdomen is soft and nontender with increased bowel sounds. The remainder of the physical examination is normal.

Laboratory studies:

Hemoglobin	12.2 g/dL (122 g/L)
Leukocyte count	9300/μL (9.3 × 10⁹/L) with normal differential
Alanine aminotransferase	120 U/L
Aspartate aminotransferase	160 U/L
Creatinine	1.2 mg/dL (106.1 μmol/L)
Fecal occult blood test	Negative

Hemoglobin	12.2 g/dL (122 g/L)
Leukocyte count	9300/μL (9.3 × 10⁹/L) with normal differential
Alanine aminotransferase	120 U/L
Aspartate aminotransferase	160 U/L
Creatinine	1.2 mg/dL (106.1 μmol/L)
Fecal occult blood test	Negative

A chest radiograph is normal and abdominal films show nondilated bowel loops with no free air.

In addition to discontinuing the ipilimumab and providing supportive care, which of the following is the most appropriate next step in treatment?

A. Broad-spectrum intravenous antibiotics

B. Granulocyte-macrophage colony-stimulating factor

C. High-dose intravenous glucocorticoids

D. Observation

Correct Answer

C. High-dose intravenous glucocorticoids

Educational Objective

Manage ipilimumab-induced toxicity.

Critique

Initiation of high-dose intravenous glucocorticoids and aggressive supportive care in addition to discontinuing the offending medication is the most appropriate treatment for this patient with ipilimumab toxicity with severe diarrhea and evidence of autoimmune hepatitis. Ipilimumab is a new class of antineoplastic therapy that inhibits the function of T-cell checkpoint receptors (ipilimumab or PD-1 and PD-L1 inhibitors), thereby enhancing the function of the immune system and inducing remissions in patients with various solid tumors, particularly metastatic melanoma. However, T-cell checkpoint inhibitors also can cause many potentially permanent and life-threatening organ toxicities that are autoimmune-mediated based on their enhancement of immune function. These include dermatologic (rash, mucositis), gastrointestinal (diarrhea, colitis), liver (autoimmune hepatitis), and endocrine (hypothalamic/pituitary, thyroid, and adrenal insufficiency). Other organ involvement (eye, kidney, hematologic, pulmonary, and neurologic) has also been reported. Because the toxicity results from triggering an exaggerated immune response, treatment of these toxicities involves removing the causative agent and providing immunosuppression, preferably with high-dose glucocorticoids due to their nonspecific immune-suppressing effects and rapid onset of action. Recognition of the autoimmune effect of the treatment is critical since the autoimmune-triggered toxicity from this class of medications can be fatal if immunosuppressive therapy is delayed.

Because the mechanism of toxicity is not directly related to leukopenia and this patient has a normal leukocyte count with no objective evidence of infection, broad-spectrum antibiotics are not indicated, and delayed recognition of the drug-related syndrome from treatment of possible bacterial infection could be detrimental.

Similarly, because the toxicity of T-cell checkpoint inhibitors is not due to leukopenia, treatment with growth factors, such as granulocyte-macrophage colony-stimulating factor, does not have a role in either the prevention or treatment of complications associated with this class of drugs.

Because rapid immunosuppression may reverse the severe autoimmune reactions triggered by ipilimumab, discontinuation of the medication and supportive care alone is inadequate therapy for this patient.

Key Point

Patients with acute ipilimumab toxicity should receive fluid replacement and immediate glucocorticoid therapy to reverse the damage this agent can cause; delay in treatment can be fatal.

Bibliography

Weber JS, O’Day S, Urba W, et al. Phase I/II study of ipilimumab for patients with metastatic melanoma. J Clin Oncol. 2008 Dec 20;26(36):5950-6.

Do you like reading Annals for Educators? Receive it direct to your inbox. Sign up for the Annals for Educators alert today.

中文翻译：

教育家年鉴-2018年1月16日。

临床实践要点

免疫检查点抑制剂在治疗癌症和自身免疫性疾病患者中的用途。系统评价

这篇系统的综述描述了接受检查点抑制剂（CPI）进行癌症免疫治疗的癌症和伴发自身免疫性疾病的患者的不良事件。

使用此评论可以：

从选择题开始教学。我们在下面提供了一个！
询问您的学习者什么是CPI。它们如何作为抗肿瘤药起作用？他们针对哪种类型的癌症被证明是成功的？邀请肿瘤科医生参加您的讨论。
为什么患有自身免疫性疾病的患者被排除在CPI的临床试验之外？CPI的作用机制为什么会导致自身免疫不良事件？
查看本研究的结果。现有数据的局限性是什么？利用作者的讨论和随附的社论来回答这个问题。
尽管有这些缺点，但本次综述中确定的观察报告如何对临床实践和进一步研究有所帮助？

当代普通人群中一级预防中他汀类药物使用的五种主要指南的比较

欧洲和北美的五个专业组织已发布使用他汀类药物预防动脉粥样硬化性心血管疾病的指南。对40至75岁的单个人群应用不同的指南将导致接受他汀类药物的参与者中只有15％或多达44％。这项研究估计了使用每条指南可以预防多少心血管事件。

使用本文可以：

询问您的学习者，他们如何决定哪些患者应使用他汀类药物进行心血管疾病的一级预防。
准则建议什么？您的学习者知道哪些知识？
查看表1，该表总结了5条主要指南中的每条指南所采取的方法。主要区别是什么？
询问您的学习者，为什么在此处建模的人群中遵循每条指南会导致推荐使用他汀类药物的患者人数不同，以及心血管事件的数量为何有所不同。
为什么指南组尽管使用了大致相同的证据，但还是发布了不同的建议？使用随附的社论来帮助您进行讨论。
您的学习者打算采用哪种方法？为什么？他们计划的方法有哪些风险和收益？

高血压患者血压控制实施策略的比较有效性。系统评价和荟萃分析

这项来自100个试验的数据的荟萃分析检验了8种实施策略对成年人高血压控制血压的相对有效性。

使用此评论可以：

询问您的学习者他们的实践中使用了哪些策略来帮助患者达到血压治疗目标。
查看表1中的实施策略列表。您的中心使用了哪些策略？在审查本研究的结果之前，请询问您的学习者他们对所列策略的执行情况有多满意。
查看结果。您的学习者感到惊讶吗？
为什么您的学习者认为某些策略比其他策略更好？
如果您所在机构的门诊实践使用基于团队的血压控制方法，那么谁参与其中？谁来监督您的实践表现？如何评估绩效？邀请质量改进人员参加您的讨论。
为什么您的学习者认为非医师团队成员的参与被认为是有用的？有哪些潜在的好处，以及阻碍他们参与的障碍？使用随附的社论来帮助您进行讨论。
登录并回答随附的问题，以自己赚取CME / MOC积分！

静脉血栓栓塞的诊断：20年的进步

这篇特别文章详细介绍了诊断成人（包括孕妇）深静脉血栓形成（DVT）和肺栓塞（PE）的最新算法。

使用本文可以：

问你的学习者为什么建立DVT或PE的预测试临床概率很重要。预测概率如何影响测验的选择和结果的解释？
您的学习者如何评估预测概率？他们是否有系统地这样做？
什么是PERC工具，什么时候有用？
查看用于评估潜在DVT和PE的算法。这些是您的学习者遵循的方法吗？为什么或者为什么不？
怀孕患者的可疑DVT或PE应该使用什么成像检查？V / Q或CT血管造影研究是否会使患者或胎儿受到更多的辐射？

因您的所作所为而获得好评

通过简单地单击并单击以查看此警报中突出显示的论文，您就有资格索取即时护理CME和MOC积分。在网站右上方登录需要花费几秒钟的时间。您登录时查看的论文将被记录下来，以便您稍后通过回答有关您如何使用内容的两个简单问题来主张CME / MOC信用。给自己应得的信誉！

MKSAP 17问题

一名55岁的妇女在急诊室接受了3天的腹泻病史评估。她每天报告七到八次大便而没有呕吐。她还注意到腹部绞痛没有呕吐，并且能够保持足够的液体摄入量。病史对于转移性恶性黑色素瘤具有重要意义，为此，她最近完成了ipilimumab治疗的四个计划剂量中的第三个剂量。她没有炎症性肠病，近期使用抗生素，近期旅行或未食用食物的病史。病史的其余部分是无贡献的，并且她没有服用其他药物。

体格检查的温度为37.5°C（99.5°F），血压为125/85 mm Hg，脉搏速率为90 / min，无立位性改变，呼吸速率为14 / min。腹部柔软而无压痛，肠鸣音增加。其余的身体检查是正常的。

实验室研究：

血红蛋白	12.2克/分升（122克/升）
白细胞计数	9300 /μL（9.3×10 ⁹ / L），带正常差
丙氨酸氨基转移酶	120个U / L
天冬氨酸转氨酶	160 U / L
肌酐	1.2 mg / dL（106.1μmol/ L）
粪便潜血测试	消极的

血红蛋白	12.2克/分升（122克/升）
白细胞计数	9300 /μL（9.3×10 ⁹ / L），带正常差
丙氨酸氨基转移酶	120个U / L
天冬氨酸转氨酶	160 U / L
肌酐	1.2 mg / dL（106.1μmol/ L）
粪便潜血测试	消极的

胸部X线片正常，腹部片显示未扩张的肠loop，没有自由空气。

除了中止ipilimumab并提供支持治疗外，以下哪项是治疗中最合适的下一步？

A.广谱静脉注射抗生素

B.粒细胞巨噬细胞集落刺激因子

C.大剂量静脉注射糖皮质激素

D.观察

正确答案

C.大剂量静脉注射糖皮质激素

教育目标

处理ipilimumab诱导的毒性。

批判

对于停用依立木单抗并伴有严重腹泻和自身免疫性肝炎证据的伊匹木单抗，最有效的治疗方法是开始大剂量静脉注射糖皮质激素和积极的支持治疗，同时还要中止有问题的药物治疗。伊匹木单抗是一类新型的抗肿瘤疗法，可抑制T细胞检查点受体（伊匹单抗或PD-1和PD-L1抑制剂）的功能，从而增强免疫系统的功能并诱导各种实体瘤患者的缓解，特别是转移性黑色素瘤。但是，T细胞检查点抑制剂还可以引起许多潜在的永久性和危及生命的器官毒性，这些毒性基于自身免疫功能的增强而由自身免疫介导。这些包括皮肤病学（皮疹，粘膜炎），胃肠道（腹泻，结肠炎），肝（自身免疫性肝炎）和内分泌（下丘脑/垂体，甲状腺和肾上腺功能不全）。也有其他器官受累（眼，肾，血液，肺和神经系统）的报道。由于毒性是由触发过度的免疫反应引起的，因此，处理这些毒性涉及去除病原体并提供免疫抑制作用，由于其非特异性的免疫抑制作用和起效迅速，因此优选使用大剂量的糖皮质激素。认识到治疗的自身免疫效果至关重要，因为如果延缓免疫抑制治疗，这类药物的自身免疫触发毒性可能是致命的。和神经系统的）也有报道。由于毒性是由触发过度的免疫反应引起的，因此，处理这些毒性涉及去除病原体并提供免疫抑制作用，由于其非特异性的免疫抑制作用和起效迅速，因此优选使用大剂量的糖皮质激素。认识到治疗的自身免疫效果至关重要，因为如果延缓免疫抑制治疗，这类药物的自身免疫触发毒性可能是致命的。和神经系统的）也有报道。由于毒性是由触发过度的免疫反应引起的，因此，处理这些毒性涉及去除病原体并提供免疫抑制作用，由于其非特异性的免疫抑制作用和起效迅速，因此优选使用大剂量的糖皮质激素。认识到治疗的自身免疫效果至关重要，因为如果延缓免疫抑制治疗，这类药物的自身免疫触发毒性可能是致命的。由于具有非特异性免疫抑制作用和起效快，因此最好与大剂量糖皮质激素一起使用。认识到治疗的自身免疫效果至关重要，因为如果延缓免疫抑制治疗，这类药物的自身免疫触发毒性可能是致命的。由于具有非特异性免疫抑制作用和起效快，因此最好与大剂量糖皮质激素一起使用。认识到治疗的自身免疫效果至关重要，因为如果延缓免疫抑制治疗，这类药物的自身免疫触发毒性可能是致命的。

由于毒性机制与白细胞减少症没有直接关系，并且该患者的白细胞计数正常，没有客观的感染证据，因此不建议使用广谱抗生素，并且从可能的细菌感染治疗中延迟识别与药物相关的综合征可能有害的。

同样，由于T细胞检查点抑制剂的毒性并非由白细胞减少症引起，因此用生长因子（如粒细胞巨噬细胞集落刺激因子）进行的治疗在预防或治疗与此类疾病相关的并发症中均无作用。毒品。

由于快速的免疫抑制可能会逆转由ipilimumab引发的严重自身免疫反应，因此仅停药和支持治疗对该患者而言是不足的治疗方法。

重点

具有急性ipilimumab毒性的患者应接受补液并立即进行糖皮质激素治疗，以逆转该药可能造成的损害；延误治疗可能是致命的。

参考书目

Weber JS，O'Day S，Urba W等。ipilimumab用于转移性黑色素瘤患者的I / II期研究。J临床Oncol。2008年12月20日； 26（36）：5950-6。

你喜欢读《教育家年鉴》吗？直接将其接收到您的收件箱。立即注册“教育者年鉴”警报。

更新日期：2018-01-16

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11