Typical Clinical manifestation and Differential diagnosis

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of clinical significance

of clinical significance“of clinical significance”这个短语通常用于医疗保健和医学研究的语境中，用来描述具有在临床环境中实际重要性或相关性的发现、结果或观察。

当某事被认为“of clinical significance”时，这意味着它对于患者病情的诊断、治疗或管理具有有意义的影响。

在评估研究结果或医学检测结果的实际影响时，这个概念是至关重要的。

For example:1.Research Findings: In clinical studies, researchers may identify a statistical differencebetween two groups. However, to be considered "of clinical significance," this difference should have a meaningful impact on patient outcomes or healthcare practices.研究结果：在临床研究中，研究人员可能会发现两组之间存在统计学差异。

然而，要被认为是“of clinical significance”，这种差异应该对患者的结果或医疗实践产生有意义的影响。

2.Diagnostic Tests: A diagnostic test may detect a slight variation in a parameter, but it is onlyconsidered "clinically significant" if that variation is relevant to the diagnosis, prognosis, or treatment decisions for the patient.诊断测试：诊断测试可能会检测到某个参数的轻微变化，但只有在这种变化对患者的诊断、预后或治疗决策具有相关性时，才被认为是“of clinical significance”。

慢性胰腺炎患者消化不良的诊治进展

慢性胰腺炎患者消化不良的诊治进展胡良皞，金震东海军军医大学第一附属医院消化内科，上海 200433通信作者：金震东，****************（ORCID：0000-0003-1196-9047）摘要：消化不良是临床常见的一组症状，可以分为器质性和功能性两类。

慢性胰腺炎（CP）时常出现脂肪泻、腹胀、腹痛等消化不良症状，其中大部分患者伴有胰腺外分泌功能不全（PEI），属于器质性消化不良。

临床上，PEI和消化不良的诊断需综合评估患者的临床表现、营养状况和胰腺外分泌功能，并以此制订个性化的治疗方案。

但部分患者外分泌功能良好却有消化不良的症状，其诊断和治疗仍为临床难点。

本文针对CP患者消化不良的诊治研究进展进行综述。

关键词：胰腺炎，慢性；胰腺外分泌功能不全；消化不良；诊断；治疗学Advances in the diagnosis and treatment of dyspepsia in chronic pancreatitis patientsHU Lianghao，JIN Zhendong.（Department of Gastroenterology，The First Affiliated Hospital of Navy Medical University，Shanghai 200433， China）Corresponding author： JIN Zhendong，****************（ORCID： 0000-0003-1196-9047）Abstract：Dyspepsia is a common group of clinical symptoms and can be classified into organic and functional dyspepsia. Patients with chronic pancreatitis （CP） often have the symptoms of dyspepsia such as fatty diarrhea， abdominal distention，and abdominal pain， and most patients have pancreatic exocrine insufficiency （PEI）， which belongs to organic dyspepsia. In clinical practice，the diagnosis of PEI and dyspepsia requires a comprehensive assessment of clinical manifestations，nutritional status， and pancreatic exocrine function， and an individualized treatment regimen should be developed based on such factors. However， some patients with normal exocrine function may have the symptoms of dyspepsia， and the diagnosis and treatment of such patients are still difficulties in clinical practice. This article reviews the advances in the diagnosis and treatment of dyspepsia in CP patients.Key words：Pancreatitis， Chronic； Exocrine Pancreatic Insufficiency； Dyspepsia； Diagnosis； Therapeutics消化不良指的是胃和十二指肠的不适症状，主要包括上腹部胀气、上腹疼痛或烧灼感、餐后饱胀及早饱、嗳气、恶心等，若存在器质性、代谢性疾病等病因（如消化性溃疡、胃肠道肿瘤、胰腺疾病、甲状腺功能亢进、药物不良反应等）则为器质性消化不良，其余无法用疾病原因解释的则为功能性消化不良［1］。

医学美容咨询的渐进性流程

医学美容咨询的渐进性流程英文回答：The progressive process of medical aesthetic consultation involves several steps to ensure that the client's needs and expectations are met. Here is a breakdown of the typical flow:1. Initial Consultation: This is the first step where the client meets with a medical aesthetician or consultant. During this consultation, the client discusses their concerns, goals, and expectations. The consultant will ask questions about the client's medical history, lifestyle, and any previous cosmetic procedures. This helps to determine the client's suitability for various treatments and to customize a plan.2. Assessment and Analysis: After the initial consultation, the medical aesthetician will conduct a detailed assessment and analysis of the client's skincondition or body concerns. This may involve examining the skin's texture, pigmentation, elasticity, or body measurements. The aesthetician may also take photographs or use specialized equipment to evaluate the client's condition.3. Treatment Options: Based on the assessment, the medical aesthetician will recommend suitable treatment options. They will explain the benefits, risks, andexpected outcomes of each treatment. The client will have the opportunity to ask questions and discuss their preferences.4. Customized Treatment Plan: Once the client has chosen the desired treatment, the medical aesthetician will create a customized treatment plan. This plan may include a series of treatments, such as laser therapy, chemical peels, injectables, or body contouring procedures. The plan will outline the number of sessions, intervals between treatments, and any necessary preparation or aftercare instructions.5. Informed Consent: Before proceeding with any treatment, the client will be required to sign an informed consent form. This form ensures that the client understands the risks, benefits, and potential side effects of the chosen treatment. It also confirms that the client has been provided with all necessary information and has given their consent to proceed.6. Treatment Sessions: The client will attend the scheduled treatment sessions as outlined in the customized plan. The medical aesthetician will perform the selected procedures, ensuring the client's comfort and safety throughout the process. Depending on the treatment,multiple sessions may be required to achieve the desired results.7. Follow-up and Maintenance: After completing the recommended treatment sessions, the client will havefollow-up appointments to assess the results and discuss any further maintenance or touch-up treatments. The medical aesthetician will provide guidance on skincare routines, lifestyle modifications, and any necessary post-treatmentcare.中文回答：医学美容咨询的渐进性流程包括以下几个步骤，以确保满足客户的需求和期望。

术前诊断英文单词

术前诊断英文单词全文共四篇示例，供读者参考第一篇示例：Preoperative diagnosis refers to the process of identifying a medical condition or disease before a surgical procedure is performed. This is an essential step in ensuring the success of the surgery and the overall health and wellbeing of the patient. Preoperative diagnosis involves a comprehensive evaluation of the patient's medical history, physical examination, and diagnostic tests to determine the precise nature of the condition that requires surgical intervention. In this article, we will discuss the importance of preoperative diagnosis, the various methods and tests used in the process, and how it impacts the overall outcome of the surgery.There are several methods and tests used in the preoperative diagnosis process, each with its own strengths and limitations. These include:第二篇示例：Preoperative diagnosis refers to the process of determining a patient's medical condition before surgery. This is a critical stepin the overall surgical process, as the diagnosis will help guide the surgeon in planning and carrying out the procedure. There are various methods and tools that can be used to make a preoperative diagnosis, including physical examinations, diagnostic tests, and medical imaging.第三篇示例：Preoperative diagnosis refers to the process of identifying a medical condition or disease before a surgical procedure. It plays a crucial role in ensuring the success of the surgery and the overall health outcomes of the patient. In this article, we will explore the importance of preoperative diagnosis and some commonly used English words related to this topic.The first step in the preoperative diagnosis process is the evaluation of the patient's medical history. This involves gathering information about the patient's past medical conditions, surgeries, allergies, medications, and lifestyle habits.A thorough review of the patient's medical history can help the healthcare team identify any potential risks or complications that could arise during surgery.Another important aspect of preoperative diagnosis is the physical examination. This involves a comprehensive assessmentof the patient's vital signs, physical appearance, and overall health status. The healthcare team may also perform specific tests and screenings to evaluate the patient's organ function, blood levels, and overall fitness for surgery.Laboratory tests are often used as part of the preoperative diagnosis process to help identify any underlying medical conditions or abnormalities. Common laboratory tests include blood tests, urine tests, imaging studies, and electrocardiograms. These tests can help the healthcare team determine the appropriate course of treatment and surgical intervention for the patient.Imaging studies, such as X-rays, CT scans, and MRIs, are also essential tools in the preoperative diagnosis process. These tests can provide detailed images of the patient's internal organs, bones, and tissues, helping the healthcare team identify any abnormalities, tumors, or other conditions that may require surgical intervention.In addition to medical tests and screenings, the healthcare team may also use diagnostic procedures such as biopsies, endoscopies, and cardiac catheterizations to further evaluate the patient's condition before surgery. These procedures can helpthe team gather more information about the extent of the disease or condition and determine the best course of treatment.Once the preoperative diagnosis is complete, the healthcare team can develop a comprehensive treatment plan for the patient. This plan may include medication management, lifestyle changes, physical therapy, and surgical intervention. The goal of the treatment plan is to optimize the patient's health andwell-being before, during, and after surgery.Commonly used English words related to preoperative diagnosis include:1. Diagnosis: The identification of a medical condition or disease based on the patient's symptoms, medical history, and test results.2. Preoperative: Referring to the period before surgery, including the evaluation, preparation, and planning for the surgical procedure.3. Evaluation: The process of assessing the patient's medical history, physical examination, and test results to determine the appropriate course of treatment.4. Medical history: A record of the patient's past medical conditions, surgeries, medications, and lifestyle habits that can help guide the preoperative diagnosis process.5. Screening: The process of testing or examining a group of people to identify those who may be at risk for a particular medical condition.6. Laboratory tests: Blood tests, urine tests, and other diagnostic tests used to assess the patient's organ function, blood levels, and overall health status.7. Imaging studies: X-rays, CT scans, MRIs, and other tests that provide detailed images of the patient's internal organs, bones, and tissues.8. Treatment plan: A detailed outline of the patient's course of treatment, including medication management, lifestyle changes, and surgical intervention.9. Surgical intervention: The use of surgery to treat a medical condition or disease, typically after a thorough preoperative diagnosis process.In conclusion, preoperative diagnosis is a critical step in ensuring the success of a surgical procedure and the overall health outcomes of the patient. By conducting a thoroughevaluation of the patient's medical history, performing physical examinations and tests, and using diagnostic procedures as needed, the healthcare team can develop a comprehensive treatment plan to optimize the patient's health and well-being. By familiarizing yourself with the commonly used English words related to preoperative diagnosis, you can better understand the importance of this process and play an active role in your own healthcare journey.第四篇示例：Preoperative diagnosis is a crucial step in the medical field, as it allows healthcare professionals to accurately assess a patient's condition before they undergo surgery. This process typically involves a series of tests and examinations to determine the nature of the patient's illness or injury, and to plan the appropriate treatment.。

临床指南中的建议整理

临床指南中的建议整理英文回答：Clinical guidelines provide evidence-based recommendations for healthcare professionals to guide their clinical practice. These guidelines are developed by expert panels and are based on a thorough review of the available scientific evidence. The recommendations aim to provide the best possible care for patients and improve health outcomes.To organize the recommendations in clinical guidelines, several steps are usually followed. First, the guideline development panel identifies the key questions that need to be addressed. These questions are typically related to the diagnosis, treatment, or management of a specific condition or disease. Once the questions are identified, a systematic review of the literature is conducted to gather theavailable evidence. This evidence is then evaluated and graded based on its quality and relevance to the clinical question.After the evidence is evaluated, the guideline panel formulates the recommendations. These recommendations are usually presented in a structured format, including the strength of the recommendation and the quality of the evidence supporting it. The strength of a recommendation indicates the level of confidence that healthcare professionals should have in the recommendation, while the quality of the evidence reflects the certainty or accuracy of the supporting evidence.In addition to the recommendations, clinical guidelines often include information on the potential benefits and harms of the recommended interventions, as well as any special considerations or circumstances that may affect the implementation of the recommendations. This additional information helps healthcare professionals make informed decisions and tailor the recommendations to individual patients.Clinical guidelines are regularly updated to incorporate new evidence and reflect changes in clinicalpractice. This ensures that healthcare professionals have access to the most up-to-date and relevant recommendations. However, it is important to note that guidelines are not meant to replace clinical judgment or individualizedpatient care. Healthcare professionals should use their expertise and consider the unique characteristics and preferences of each patient when applying the recommendations in clinical practice.中文回答：临床指南提供了基于证据的建议，以指导医疗专业人员的临床实践。

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Section Ⅱ
Acute Cholecystitis 急性胆囊炎
chole- 胆，胆汁 cholecyst: 胆囊 -itis: 炎症
Assessment
ethnic group: 种族 food preferences: 饮食爱好 …determines whether excessive fat and cholesterol are included in the diet: 确定饮食中脂肪和胆固醇是否过量 tolerate: v. 耐受 gastrointestinal (GI) symptoms:胃肠道症状 fatty food: 脂类食物

recumbent position: 卧位 heartburn: n. 烧心感 complaint: n. 疾病 palpation: n. 触诊 percussion: n. 叩诊 light palpation: 浅触诊 rebound tenderness: 反跳痛 peritoneal irritation: 腹膜刺激

meperidine: 度冷丁 hydrochloride: 氢氯化物 hydro-: 水，氢的 spasm: n. 痉挛 antispasmodic agent: 解痉药 smooth muscles: 平滑肌 biliary contraction: 胆道收缩 cholecystectomy: 胆囊切除术 laparoscopic: a. 腹腔镜的 lapro-: 腹

typical presentation: 典型的表现 clinical manifestation: 临床表现 precipitating factor: 诱发因素 indigestion of varying intensity: 不同程度的消化不良 range from… to…: 从…到… quadrant: n. 象限 radiate to: 放射 scapula: n. 肩胛骨

临床试验中增加入组以及防止患者脱落的策略

Strategies to enhance patient recruitment and retention in research involving patients with a ﬁrst episode of mental illnessIvana Furimsky a ,⁎,Amy H.Cheung b ,Carolyn S.Dewa b ,c ,Robert B.Zipursky da Mental Health and Addictions Program,St.Joseph's Healthcare Hamilton,100West 5th Street,Box 585,Hamilton,ON,Canada L8N 3K7b Department of Psychiatry,University of Toronto,Toronto,Ontario,Canadac Health Systems Research and Consulting Unit at the Centre for Addiction and Mental Health,Toronto,ON,Canada dDepartment of Psychiatry and Behavioural Neurosciences,McMaster University,Hamilton,Ontario,Canadaa r t i c l e i n f o ab s t r ac tArticle history:Received 5May 2008Accepted 28July 2008Recruitment and retention of research participants is often the most labor-intensive and dif ﬁcult component of clinical trials.Poor recruitment and retention frequently pose as a major barrier in the successful completion of clinical trials.In fact,many studies are prematurely terminated,or their ﬁndings questioned due to low recruitment and retention rates.The conduct of clinical trials involving youth with a ﬁrst episode of mental illness comes with additional challenges in recruitment and retention including barriers associated with engagement and family involvement.To develop effective early interventions for ﬁrst episode mental illness,it is necessary to develop strategies to enhance recruitment and retention in this patient population.This article presents the recruitment and retention challenges experienced in two clinical trials:one involving participants experiencing a ﬁrst episode of depression and one involving participants experiencing a ﬁrst episode psychosis.Challenges with recruitment and retention are identi ﬁed and reviewed at both the patient level and clinician level.Strategies that were implemented to enhance recruitment and retention in these two studies are also discussed.Finally,ethical issues to consider when implementing these strategies are also highlighted.©2008Elsevier Inc.All rights reserved.Keywords:Recruitment Retention Clinical trial Psychosis Depression First episode1.IntroductionMental illnesses frequently present for the ﬁrst time in adolescence or young adulthood [1].Early identi ﬁcation of these disorders may improve outcomes in adulthood [2–4].Wright and Russell [5]conducted a systematic review of interventions for psychosis in adolescents,and found that many of the interventions used in this patient population are reliant on evidence from studies conducted with adults.They highlighted the fact that clinical trials relating speci ﬁcally to youth are required to provide evidence for treating youth in the same way as adults.However,due to many barriers,including dif ﬁculty with the conduct of clinical trials,there is no de ﬁnitive evidence that early detection and intervention can improve prognosis.As a result,most of the clinical interventions used in the ﬁrst episode population are not well researched and there is limited evidence on which to base best practices [2,6].A major barrier to the conduct of clinical trials in this population relates to the recruitment and retention of research subjects.The problem with recruitment and retention is not speci ﬁc to studies involving ﬁrst episode populations [6–8].Recruitment of research participants often represents the most labor-intensive component of a research project.Studies that have examined the effectiveness of solutions to overcome problems with recruitment and retention have generally found few strategies to be effective [8–10].In a systematic literature review,Ross et al [11]identi ﬁed barriers to participation in RCTs in a variety of patient populations.Barriers were encountered at the clinician and at the patient level.Contemporary Clinical Trials 29(2008)862–866⁎Corresponding author.Tel.:+19055221155x36774;fax:+19053815601.E-mail addresses:ifurimsk@stjoes.ca ,ivanafurimsky@ (I.Furimsky).1551-7144/$–see front matter ©2008Elsevier Inc.All rights reserved.doi:10.1016/t.2008.07.005Contents lists available at ScienceDirectContemporary Clinical Trialsj o u r n a l h o me p a g e :w w w.e l sev i e r.c o m /l oc a t e /c on c l i n t r i a lIn the most recent Cochrane review,Mapstone and colleagues reviewed studies that evaluated strategies to improve recruitment to research studies[9].Their review focused on recruitment strategies for RCTs.In total,15studies evaluating5types of strategies were reviewed.The5types of strategies were:1)pre-warning(i.e.,patient receives study information prior to being approached for recruitment),2)extra information given at the time of consent,3)change in study design,4)changes in consent process,and5)monetary incentives.Two strategies were found to be effective in improving recruitment into RCTs.First,the use of incentives for subjects to participate in research studies was found to improve recruitment.A second strategy that was also found to be effective in improving recruitment involved artiﬁcially manipulating the magnitude of the difference in efﬁcacy between an experimental treatment compared to the standard treatment.That is,when patients were told that the experi-mental treatment worked two times faster than the standard treatment,they were more likely to participate in the study. However,the authors of the review questioned the strategy's applicability in real-world settings.In their review,the authors were not able to identify any studies that evaluated recruitment strategies for patients with mental illness.In this paper,we examine major challenges to recruitment and retention for RCTs with youth presenting with theirﬁrst episodes of major mental illness.We will speciﬁcally focus on issues that are the most relevant to this population.Little has been published describing the challenges encountered in conducting research in youth.This paper draws from experiences from two RCTs that were conducted with individuals experiencing early onset of2mental illnesses, depression and ing examples from these studies, we will describe both the challenges,and the strategies that we found effective in addressing the challenges with recruit-ment and retention in this population.1.1.Description of twoﬁrst episode RCTsTheﬁrst study we will describe in this paper is a12-month RCT conducted in a First Episode Psychosis program in a large psychiatric teaching hospital in Toronto,Canada.It was conducted from2003–2005.The purpose of the study was to evaluate a mobile treatment team for young people experien-cing theirﬁrst psychotic episode.The comparison program was theﬁrst episode psychosis outpatient clinic.Henceforth,the study will be referred to as the psychosis study.The second study is a clinical trial for adolescent depres-sion conducted in5tertiary care settings across Canada.This study examined the beneﬁt of citalopram in adolescents with depression and was conducted from2004–2007.There were2 phases to the study:1)12-week acute phase and2)24-week continuation phase.Subjects who responded to open label treatment of citalopram in the acute phase were randomized to either citalopram or placebo during the continuation phase. Throughout this paper,this study will be referred to as the depression study.Ethics approval was obtained from the respective institu-tions where the studies were conducted(Sunnybrook Health Sciences Centre and the Centre for Addiction and Mental Health,Toronto,Canada).Each participant provided informed consent.2.Challenges2.1.Recruitment2.1.1.Patient acceptance of the diagnosisSeveral factors hindered the recruitment of subjects in theirﬁrst episode of psychosis or depression.First,during the early stage in the course of their treatment for a newly diagnosed mental illness,many patients are trying to under-stand the implications of their diagnosis,the treatment options,and the roles of the various clinicians in their care [12].It may also take time for patients to develop insight into their illness and accept the diagnosis.Enrolling in a study is problematic if the patient has not accepted the diagnosis already.In the psychosis study,30%of the patients who were eligible for the study and were approached to participate refused psychiatric services of any kind.2.1.2.Family acceptance of the diagnosisManyﬁrst episode patients are at a stage in life when they may still be dependent on the resources of their families of origin including housing,money and transportation.Family members may work full-time and may not be able to take time off work to bring patients to study appointments.This has been shown to be signiﬁcant barrier to enrollment and retention in clinical trials[13].Family support is a critical element of early engagement into outpatient treatment[12]. Therefore,both the patients'and families'acceptance of the diagnosis and treatment are critical to full participation in research studies.Ross et al[11]also identiﬁed that patients were less likely to participate in research if someone important to them was against it.This highlights the fact that strategies to improve recruitment must address barriers with both the patients and their families.In the depression study,50%of the eligible subjects declined enrollment because of concerns from parents/family members.2.1.3.Extra burden of additional study visitsManyﬁrst episode patients are enrolled in school and due to their illness,are likely to be already struggling to maintain their academic status[14,15].Therefore,taking time from school to come to research or clinic appointments can signiﬁcantly impact on their academic endeavors.Although this may be especially problematic in theﬁrst episode population,the extra burden of appointments and procedures involved with parti-cipation in a research study has been shown to be a major barrier to research participation in other patient populations [11].This issue was raised by many of the parents of eligible subjects in the depression study as the reason for refusing participation.In fact,this issue was also raised by all of the subjects who agreed to participate who were also enrolled in school full-time.In the psychosis study,missing school or work was also a concern for most patients and their families.2.1.4.Reluctance of clinicians to refer their patients to researchAnother set of barriers relate to clinicians who are treating the patient population[6,11].Front-line clinicians are the most logical referral sources for potential study participants. However,during the initial stages of treatment when they are developing therapeutic alliance with their patients,some clinicians may be reluctant to enroll their patients in RCTs for863I.Furimsky et al./Contemporary Clinical Trials29(2008)862–866fear that enrollment will impede engagement[7].Previous research in other areas of medicine also identiﬁes inter-ference with the doctor–patient relationship as a signiﬁcant barrier to clinicians encouraging research participation[11]. Given the nature of the therapeutic relationship between mental health clinicians and their patients,this issue may be even more relevant in this population.Furthermore,partici-pation may create extra work demands for the clinician and the protocol may be incompatible with usual practice[7,11]. Therefore,if clinicians do not feel that the research is important,they will be reluctant to support the study because of the extra time and effort required.In the depression trial,the clinicians'willingness to participate signiﬁcantly impaired recruitment.In the largest study site with7full-time physicians who had over200new depression referrals annually,only19subjects were recruited over the course of the study,while a smaller site with only one physician,recruited24subjects.Out of the110admissions to the First Episode Psychosis Program,the psychosis study team was able to make arrangements with the clinicians to speak with85%of the admissions that were thought to be eligible for the study.In the end,43%of these patients agreed to participate in the psychosis study.2.2.Retention of subjects2.2.1.Decreased need for treatmentRetention of subjects can also be a signiﬁcant challenge in the conduct of RCTs.Over time,a patient's motivation to remain in a study may decrease.Reasons that may inﬂuence a patient's decision to drop out of a research study include:failing to respond to the treatment being studied,side effects,added appointments/expenses,and incompatibilities of the protocol with usual clinical practice[11].Like most clinical trials subjects,ﬁrst episode patients are reluctant to continue in a study when their symptoms have improved or resolved.Some patients ﬁrmly believe that once their initial episode of psychosis has resolved,they will never experience another episode again and as a result,many will stop treatment[16].In the psychosis study 8%of the patients withdrew because they did not feel they had a serious mental illness that required continuous care.In addition,patients'families may also see the improve-ment in symptoms and functioning as a‘cure’and therefore, discourage patients from returning for follow-up or continue with treatment[17].This is especially signiﬁcant in long-term studies such as the depression study where subjects discon-tinued the study because their depression had improved and they no longer wanted to take the medication.In the depression study,the drop out rate was highest among those who responded to treatment and were then rando-mized to continuation treatment or placebo.In total,20out of 60subjects who responded dropped out of the study.3.Solutions3.1.Integration of research and treatment teams3.1.1.Introducing the idea of research at theﬁrst appointmentDuring the course of the two studies,several strategies were effective in overcoming the challenges with recruit-ment and retention.Introducing the research study at the patient'sﬁrst point of contact with mental health services is important in identifying eligible patients.In the psychosis study,the treatment team would tell the patient that a member of the research team would come and speak to them to discuss opportunities to participate in research.At initial assessments,the research staff should be introduced to all potential subjects as a key component of the overall program of care for patients.This strategy is similar to pre-warning, identiﬁed by Mapstone et al[9],where patients received information,by mail or phone,prior to being approached for participation.The authors of the review did notﬁnd pre-warning to be an effective strategy to increase recruitment in RCTs.However,in the psychosis study,93potentially eligible patients were approached by the research team after the treatment team introduced the idea of research. Verbal pre-warning by the treatment team also showed patients,that the treatment team and research teams were working together,which may further enhanced engagement with patients.3.1.2.Research team provides research information and obtains consentWhile integration of research and treatment teams aids in the recruitment and retention of patients in clinical trials, some ethical issues pertaining to the roles of the two teams, need to be acknowledged.Firstly,research participation is a personal,voluntary choice and there should not be any undue inﬂuence on a patient's decision to participate in research [18].The treatment team's primary responsibility was to advocate for what was in the patient's best interest and the patient needed to be conﬁdent that their treatment team was acting in their best interest and not balancing their needs with the research team's needs to recruit study participants. To avoid potential conﬂict of interest,the treatment team was not involved in obtaining consent to participate in research. This role was designated to a member of the research team who was not involved in the patient's care[19].In the psychosis study,the treatment team brieﬂy introduced the study to their patients.If a patient expressed an interest in the study,a member of the research team met with them to further discuss participation.The researcher also obtained consent when the patient was willing to enroll and offered the patient the option of having their clinician present to support them throughout this process.3.1.3.Streamlining clinical and research assessmentsThe integration of the research and treatment teams may also facilitate the engagement and assessment of patients and their families.In both the psychosis and depression studies, the results of research assessments were provided to the treatment team to enhance their efforts at diagnosis and treatment planning.In fact,this advantage has often been cited by families of children participating in research as a reason for participation[13].Also,by streamlining the initial research and clinical assessments,the time burden of an additional research assessment can be alleviated,particularly if family involvement is needed.In subsequent visits,the research appointments can be scheduled on the same day as clinical visits and this can decrease the total number of trips made to the clinic.In the psychosis study,we aimed to decrease the amount of times the patient had to come to the864I.Furimsky et al./Contemporary Clinical Trials29(2008)862–866clinic and therefore,we made an effort to always schedule study visits the same day as the visit with the treatment team.3.1.4.Sharing patient information between the treatment and research teamsA patient's decision to participate in research should be kept conﬁdential and all efforts should be made to protect research participants'information[20].This issue was con-sidered during the process of integrating the research and treatment teams.Since much of the research inﬁrst episode mental disorders involves interventions such as medications or psychotherapies,the safety of the patient may be com-promised if the treatment team is not aware that their patient may be receiving a particular intervention.Therefore,dis-closure of study participation and personal health informa-tion collected as part of the study were shared with the treatment team.Vise a versa,the treatment team provided the research team with additional information about the patient's progress.In the psychosis study,sharing of personal health information in this manner was approved by the research ethics board as long as the patients were fully informed that this was going to take place.In turn,the informed consent document included this information,as well,the researcher made sure that the patient understood this during the consent process.3.1.5.LeadershipHowever,integration is often a difﬁcult task.The most effective integration is when both the treatment and research teams have a common goal.This is most likely to be the case if the teams have similar leadership.This was seen in the depression study where at one site,the same clinician led both the treatment and research teams.The retention was the greatest at that particular site.Also in the psychosis study,the same clinician provided leadership to both teams and at this site,members of the research team met regularly with the treatment team.3.2.Incentives3.2.1.Financial compensationIn their review,Mapstone et al found that monetary incentive tended to improve recruitment in RCTs[9].In the psychosis study we found thatﬁnancial incentives helped in the recruitment process.Patients were offered transportation costs andﬁnancial compensation for the time it took to complete the study procedures.3.2.2.Volunteer creditAn incentive for the adolescents in the depression study was the volunteer credit patients received for participating in the research study.In some jurisdictions,volunteer experi-ences are required for high school graduation.The volunteer credit encouraged both patients and their families to come to appointments with the treatment/research team.This credit was especially helpful with retention after patients improved with treatment and had less motivation to attend appoint-ments.In the depression study,recruitment was improved with incentives.Approximately5%of subjects agreed to participate after learning about the provision of the volunteer credit they would receive for participation.3.2.3.Access to treatmentA controversial incentive is access to treatment.For many patients,access to care may be signiﬁcantly improved if they agree to participate in a research study.This is particularly relevant toﬁrst episode patients with depression compared with patients with psychosis,who tend to have more access to integrated services.In certain regions,participation in a research study may be the only way to access treatment.This issue needs to be addressed by local ethics boards but currently it is an accepted practice.In the depression study, several family physicians referred their patients to the study because it expedited their patients'access to mental health services by2–3months compared to if they were referred through the standard intake route.These referrals made up approximately15–20%of screened participants in the study. In the psychosis study,this was not seen as an incentive,since patients would have still received treatment for their illness if they chose not to participate in the study.3.3.Flexibility in scheduling study visitsFlexibility in scheduling appointments was identiﬁed by Aitken et al[10]as a major factor in increasing recruitment and retention of research participants.In the psychosis study,the research team accommodated study participants'work and school schedules by arranging study visits in the evenings and on weekends,if necessary.In the end,only one subject was lost due to not having the time to come for the study visits.4.LimitationsThe challenges identiﬁed in this paper focus on a popula-tion of patients that are in their teens and early twenties with a ﬁrst episode of mental illness.However,we feel that many similar challenges can be identiﬁed within an older patient population with other diagnosis.The reluctance of clinicians to refer patients to research may be increased in aﬁrst episode mental illness population compared to other populations of patients who may have more chronic conditions.Some of the solutions identiﬁed in this paper may not be effective in other patient populations.For example,volunteer credits may not be an incentive to patients that are not in school.Also in some jurisdictions,where there are many similar services,access to treatment would not be an incentive.We also note that integration of the two teams can be more easily accomplished in a setting where the teams work in close proximity and where the leadership may be similar.5.ConclusionsThis paper discusses two of the most challenging aspects of conducting research in theﬁrst episode of mental illness population.The challenges and solutions described in this paper are speciﬁc to these two RCTs and the sites where they were conducted.The challenges identiﬁed focused on the patient,family and clinicians.The solutions identiﬁed focused on integrating the research and treatment teams,the use of incentives andﬂexibility in scheduling.We found two strategies identiﬁed in the Cochrane review[14],pre-warning and monetary incentives,to be useful in recruitment of patients.865I.Furimsky et al./Contemporary Clinical Trials29(2008)862–866Although innovative strategies may address many of the barriers to recruitment and retention,there are other barriers that may be context speci ﬁc and cannot be generalized from the studies reviewed in this paper.An example is the possible adverse effects from speci ﬁc treatments that may in ﬂuence recruitment and retention.Other barriers such as stigma can be partially circumvented through speci ﬁc strategies on the study level but will only be fully addressed through large-scale public health initiatives to increase awareness and acceptance of mental illness.It is our hope that in writing this paper,new challenges and solutions have been identi ﬁed which may help other research teams.Given the lack of research evidence to support the use of speci ﬁc strategies to improve recruitment and retention in clinical trials,the strategies developed from these two RCTs should be evaluated in clinical trials in order to demonstrate their potential ef ﬁcacy.AcknowledgementsBoth studies reviewed in this manuscript were funded by the Canadian Institutes of Health Research (CIHR)(Psychosis study —grant HSM-52358).Dr.Dewa gratefully acknowledges funding from the CIHR/PHAC Applied Public Health Chair.Dr.Cheung would like to acknowledge generous salary support from the Randomized Controlled Trials Committee Mentoring Program.References[1]Kessler RC,Wang PS.The descriptive epidemiology of commonlyoccurring mental disorders in the United States.Annu Rev Public Health 2008;29:115–29.[2]Marshall M,Rathbone J.Early intervention for psychosis.CochraneDatabase Syst Rev 2004(2)___________________________________,doi:10.1002/14651858.CD004718.pub2.[3]Lieberman JA.Investigating the early stages of schizophrenia.In:Zipursky RB,Schulz SC,editors.The early stages of schizophrenia.American Psychiatric Publishing,Inc;2002.p.55–77.[4]McGlashan T.Early detection and intervention of schizophrenia:rationale and research.Br J Psychiatry 1998;172(supplement 33):3–6.[5]Wright S,Russel P.Interventions for psychosis in adolescents (protocol).The Chochrane Library 2007(3)______________________________,doi:10.1002/14651858.CD004965.[6]Hinshaw SP,Hoagwood K,Jensen PS,et al.AACAP 2001research forum:challenges and recommendations regarding recruitment and retention of participants in research investigations.J Am Acad Child Adolesc Psych 2004;43(8):1037–45.[7]Fayter D,McDaid C,Eastwood A.A systematic review highlights threatsto validity in studies of barriers to cancer trial participation.J Clin Epidemiol 2007;60:990–1001.[8]McDaid C,Hodges Z,Fayter D,et al.Increasing participation of cancerpatients in randomised controlled trials:a systematic review.Trials 2006;7:16Published online.[9]Mapstone J,Elbourne D,Roberts I.Strategies to improve recruitment toresearch studies (review).The Chochrane Library 2008(1)___________,doi:10.1002/________________________14651858.MR000013.pub3.[10]Aitken L,Gallagher R,Madronio C,et al.Principles of recruitment andretention in clinical trails.Int J Nurs Pract 2003;9:338–46.[11]Ross S,Grant A,Counsell C,Gillespie W,Russell I,Pescott R.Barriers toparticipation in randomised controlled trials:a systematic review.J clin Epidemiol 1999;52:1143–56.[12]Compton SN,March JS,Brent D,Albano AM,Weersing R,Curry J.Cognitive-behavioral psychotherapy for anxiety and depressive dis-orders in children and adolescents:an evidence-based medicine review.J Am Acad Child Adolesc Psych 2004;43:930–59.[13]van Stuijvenber M,Suur JH,de Vos S,et rmed consent,parentalawareness,and reasons for participating in a randomized controlled study.Arch Dis Child 1998;79(2):120–5.[14]Vitiello B,Rohde P,Silva S,et al.Functioning and quality of life in theTreatment for Adolescents with Depression Study (TADS).J Am Acad Child Adolesc Psych 2006;45(12):1419–26.[15]Addington J,van Mastrigt S,Hutchinson J,Addington D.Pathways tocare:help seeking behavior in ﬁrst episode psychosis.Acta Psychiatr Scand 2002;106:358–64.[16]McCay E,Ryan K.Meeting the patient's emotional needs.In:ZipurskyRB,Schulz SC,editors.The early stages of schizophrenia.American Psychiatric Publishing,Inc.;2002.p.107–27.[17]Czuchta DM,McCay E.Help-seeking for parents of individualsexperiencing a ﬁrst episode of schizophrenia.Arch Psychiatr Nurs 2001;15(4):159–70.[18]National Commission for the Protection of Human Subjects ofBiomedical and Behavioural Research.The Belmont Report.Washing-ton,DC:US Government Printing Of ﬁce;1978.DHEW prublication OS-78-0012.[19]Canadian Institutes of Health Research,Natural Sciences and Engineer-ing Research Council of Canada,social Sciences and Humanities Research Council of Canada.Section 2:Free and Informed Consent.In the Tri-Council Policy Statement:Ethical Conduct for Research Involving Humans,1998(with 2000,2002,2005amendments).[20]Canadian Institutes of Health Research,Natural Sciences and Engineer-ing Research Council of Canada,social Sciences and Humanities Research Council of Canada.Section 3:Privacy and Con ﬁdentiality.In the Tri-Council Policy Statement:Ethical Conduct for Research Involving Humans,1998(with 2000,2002,2005amendments).866I.Furimsky et al./Contemporary Clinical Trials 29(2008)862–866。

侵袭性肺部真菌感染的实验室检测方法

专家述评侵袭性肺部真菌感染的实验室检测方法郭鹏豪，廖康，伍众文，何宇婷，陈怡丽，刘敏基金项目：中山大学校级本科教学质量工程类建设项目(编号：80000-18832601)作者单位：510080广州，中山大学附属第一医院医学检验科作者简介：郭鹏豪(1984-),男，医学硕士，副主任技师，研究方向:真菌的流行病学及耐药机制。

**********************通讯作者；刘敏(1964-),女，大学本科，医学学士，主任技师，研究方向:感染及肿瘤标志物研究。

E-mail：137****************刘敏，中山大学附属第一医院医学检验科主任，中山大学医学检验学系主任。

本科毕业于中山大学中山医学院医学系临床医学专业,研究方向为感染及肿瘤标志物研究。

担任广东省医师协会检验医师分会、医院协会临床实验室管理专委会、精准医学应用学会精准检测分会、生物工程学会临床实验室分会、预防医学微生物及免疫分会、医疗行业协会检验分会、健康管理学会检验分会副主任委员；中国女医师协会检验分会常委;广东省女医师协会检验分会主任委员；中国医师协会检验医师分会委员。

主要从事临床医学检验、教学和科研及临床实验室管理等方面的工作，尤其是在感染、肿瘤标志物、自身免疫及产前筛查等方面有丰富的经验。

承担或参与国家自然科学基金项目、863子课题项目、广东省科技厅项目及广州市协同创新重大专项基金项目等多项课题，发表SCI收录及中文核心期刊等论文数十篇。

其中2020年在BMJ以第一作者发表Use of p ersonal protective equipment against coronavirus disease2019by healthcare professionals in在《中华检验医学杂志》上以通讯作者发表文章《不同方式灭活口咽拭子标本对2019新型冠状病毒实时荧光定量PCR检测结杲的影响》，参与的项目“新型冠状病毒肺炎综合防控诊治体系"获广东省科技进步一等奖。

内科学_支气管哮喘-陈小东

Etiology
•The pathogenesis of asthma is complicated •Affected by genetics and the environment •It is a multigene disorder and closely related to atopy •Most patients have prior history of eczema, allergic rhinitis, food or drug allergy, and quite a few patients have family history •The formation and attack of asthma is also a consequence of the function of multiple environmental factors such as inhalation of allergens, respiratory tract virus infection, and coldness
Hyper-reactivity of the airway
• Bronchial reactivity refers to the contractive reaction of the airway to various stimuli including those chemical, physical or pharmacologic in nature
Endocrine factors
Asthma disappears in puberty in some patients; aggravated in menstruation period , during pregnancy, and when there is hyperthyroidism

急性播散性脑脊髓炎伴结核性脑膜炎一例

·论　著·急性播散性脑脊髓炎伴结核性脑膜炎一例邢君娜　孔　鹏　武彦敏　刘　婷　李　彬【摘要】　目的　探讨急性播散性脑脊髓炎（ADEM）伴结核性脑膜炎1例的临床表现及治疗。

方法　患者男31岁，以腰部及双下肢疼痛13d，双下肢麻木伴乏力6d，小便障碍4d收入河北医科大学第二医院神经内科。

既往“乙型肝炎”病史31年。

入院后行颈髓MRI示脊髓内异常信号，头颅增强MRI考虑脱髓鞘病变，腰椎穿刺示脑脊液蛋白及淋巴细胞增加，结合临床表现、实验室及典型的影像学特征考虑ADEM，给予丙种球蛋白0.4g·kg-1×3d，甲泼尼龙1000mg·d-1×3d冲击治疗，并逐渐减量，随后继续口服泼尼松治疗。

患者症状明显好转，但仍持续间断低热，最高达37.5℃。

为明确病因，复查脑脊液（CSF）及结核相关抗体检查，抗酸染色阳性，结核相关抗体阳性，立即给予异烟肼、利福平、吡嗪酰胺、乙胺丁醇，抗结核治疗，患者无发热，病情明显好转，可自行行走，并遵医嘱出院。

结果　①本例患者临床表现、头颅及颈髓MRI符合ADEM的诊断，给予大剂量激素冲击治疗有效；②复查患者CSF细胞学，抗酸染色阳性，检测结核相关抗体阳性，考虑抗酸染色阳性杆菌感染；③给予抗结核治疗后，患者体温恢复正常，病情明显缓解，可自行行走，表明抗结核治疗有效。

结论　本例患者自出生即有乙型肝炎病毒感染，机体免疫功能紊乱，ADEM作为自身免疫性疾病，患者自身免疫机能受损与ADEM的发生发展密切相关，此外还伴有抗酸染色阳性杆菌感染，且抗结核治疗有效，而此类病例目前尚未见报道。

因此，当临床ADEM病因不明确时，可筛查乙型肝炎、结核分枝杆菌感染，进一步明确诊断及鉴别诊断，早期治疗，改善患者预后。

【关键词】　急性播散性脑脊髓炎；抗酸染色阳性杆菌；结核性脑膜炎中图分类号：R529.3 文献标识码：A 文章编号：1006-351X（2019）09-0568-06One case of acute disseminated encephalomyelitis with acid-fast staining positive bacilli infection Xing Junna,Kong Peng, Wu Yanmin, Liu Ting, Li Bin. Department of Neurology, the Second Hospital of Hebei Medical University, KeyLaboratory of Hebei Neurology, Shijiazhuang 05000, ChinaCorresponding author:Li Bin, Email: jack511@【Abstract】Objective To investigate the clinical manifestations and treatment of acute disseminated encephalomyelitis （ADEM） with acid-fast staining-positive bacilli infection. Method　A 31-year-old manexperienced the pain in the waist and lower limbs for 13 days, numbness in both lower limbs with fatigue for 6 days,and with dysuria for 4 day. His MRI and cerebrospinal fluid （CSF） were done on the second hospital day. Cervicalspinal MRI showed abnormal signal in the spinal cord, brain-enhanced MRI considering demyelinating lesions. Wedid a lumbar puncture and found there is a protein and lymphocytes increased in the CSF. Combined with his clinicalmanifestation, CSF and typical imaging features, he was diagnosed ADEM. The immunoglobulin （0.4 g·kg-1 for 3days）, methylprednisolone pulse therapy （1,000 mg·d-1 for 3 days） were given, and gradually reduced, followed byoral prednisone, the patient's clinically symptoms improved. But the patient continued to have a fever, up to 37.5℃.To find the reason, then the cerebrospinal fluid acid-fast staining and tuberculosis-related antibody were reexamined.His acid-fast staining is positive, and some tuberculosis-related antibody were positive too. Then the isoniazid,rifampicin, pyrazinamide, ethambutol, 4 anti-tuberculosis treatment were immediately given. After given that, the patient基金项目：国家自然科学基金资助项目（81471228）作者单位：050000 石家庄，河北医科大学第二医院神经内科，河北省神经病学重点实验室（邢君娜、刘婷、李彬）；邯郸市第一医院（孔鹏）；德国哥廷根大学（武彦敏）通信作者：李彬，Email：jack511@急性播散性脑脊髓炎（acute disseminated encephalomyelitis，ADEM）是一种广泛累及中枢神经系统（central nervous system，CNS）白质的急性炎症性脱髓鞘疾病。

阑尾炎临床诊断金标准

阑尾炎临床诊断金标准英文回答：The clinical diagnosis of appendicitis is primarily based on the patient's symptoms, physical examination findings, and laboratory tests. However, there is no single gold standard for the diagnosis of appendicitis, as the presentation can vary widely among individuals. The accuracy of the diagnosis depends on the experience and expertise of the healthcare provider.Typically, the most common presenting symptom of appendicitis is abdominal pain, which usually starts around the umbilicus and then migrates to the right lower quadrant of the abdomen. The pain is often described as sharp and constant, and it may be worsened by movement or coughing. Other symptoms that may accompany the pain include nausea, vomiting, loss of appetite, and low-grade fever.During the physical examination, the healthcareprovider may perform several tests to assess for signs of appendicitis. These include the rebound tenderness test, where pressure is applied to the abdomen and then quickly released, causing pain when the inflamed appendix rebounds against the peritoneum. The healthcare provider may also check for a positive psoas sign or obturator sign, which are indicative of irritation of the adjacent muscles due to inflammation of the appendix.Laboratory tests, such as a complete blood count (CBC), may be performed to evaluate for an elevated white blood cell count, which is a common finding in appendicitis. However, it is important to note that an elevated white blood cell count is not specific to appendicitis and can be seen in other conditions as well.Imaging studies, such as ultrasound or computed tomography (CT) scan, may be ordered to further evaluate the appendix and surrounding structures. These imaging modalities can help confirm the diagnosis of appendicitis and rule out other possible causes of abdominal pain.In some cases, a clinical scoring system, such as the Alvarado score or the Pediatric Appendicitis Score (PAS), may be used to help assess the likelihood of appendicitis. These scoring systems take into account various clinical factors, such as symptoms, physical examination findings, and laboratory results, to provide a numerical score that indicates the probability of appendicitis.It is important to note that the clinical diagnosis of appendicitis is not always straightforward, and there can be cases where the diagnosis remains uncertain even after a thorough evaluation. In such cases, the healthcare provider may opt for a watchful waiting approach or may recommend exploratory surgery to definitively diagnose and treat the appendicitis.中文回答：阑尾炎的临床诊断主要依据患者的症状、体格检查结果和实验室检测。

【医学ppt课件】化脓性脑膜炎(英文版)

stain +
Viral
Normal or Normal Normal or Normal or normal
-
土
meningitis/
个
个
个
encephalitis
(MN)
(<1)
Байду номын сангаасFungal
Normal or Normal
个
个
meningitis
个
or
(MN)
cloudy
India ink 土 prep +
Cerebrospinal fluid in neurologic infection
Disease
normal
Pressure (Kpa)
0.69-1.96 (0.29-0.78)
aspect clear
Total WBC (x106/L)
0-5 (0-20)
Protein (g/L)
0.2-0.4 (0.2-1.2)
. Tuberculous meningitis Subacute onset and progress A history of close contact with known cases of tuberculosis Evidence of acute or healed tubercular infection on chest x-ray Tuberculin skin test : PPD CSF
. Subacute onset: Precede by several days of upper respiratory tract or gastrointestinal symptoms; difficult to pinpoint the exact onset of meningitis; usually with meningitis due to Haemophilus influenzae ( H influenzae) and streptococcus pneumococcus ( S pneumococcus) .

疾病检查的一般流程

疾病检查的一般流程When it comes to the general process of disease testing, it is important to understand that it typically involves several key steps. 说到疾病检查的一般流程，重要的是要理解通常涉及几个关键步骤。

From the initial consultation with a healthcare provider to the actual testing procedures, each stage plays a crucial role in determining the individual's health status. 从与医疗保健提供者的初步咨询到实际的检测程序，每个阶段都在确定个人的健康状况方面发挥着至关重要的作用。

One of the first steps typically involves discussing symptoms and medical history with a healthcare professional. 通常，第一步涉及与医疗专业人员讨论症状和病史。

This initial consultation helps the healthcare provider understand the individual's concerns and develop a personalized testing plan. 这次初步咨询帮助医疗保健提供者了解个体的关注点，并制定个性化的检测计划。

It is crucial for individuals to provide accurate and detailed information during this stage to ensure the most effective testing process. 在这个阶段，个人提供准确和详细的信息至关重要，以确保最有效的测试过程。

外周动静脉畸形的治疗

EVIDENCE SUMMARYPeter wrence,MD,Section EditorEvaluation and management of congenital peripheral arteriovenous malformationsNaiem Nassiri,MD,a Nolan C.Cirillo-Penn,BA,b and Jones Thomas,BA,b New Brunswick,NJThe International Society for Study of Vascular Anomalies(ISSVA)broadly categorizes vascular anomalies into vascular tumors and vascular malformations.Vascular malformations are further divided based on theirﬂow properties into slow-ﬂow venous and lymphatic malformations,high-ﬂow arteriovenous malformations(AVMs),and congenital mixed syn-dromes,which can include combinations thereof.Whether occurring in isolation or as part of a broader syndrome, congenital high-ﬂow AVMs are arguably the most complicated,challenging,and gratifying of all vascular malformations to diagnose and manage.Various conﬁgurations exist depending on location and coexisting clinical features.Trans-catheter embolization has evolved into the mainstay of treatment for most congenital peripheral AVMs with surgical excision playing a growingly limited role as an adjunctive modality.Successful treatment requires technical precision, creativity,patience,and persistence given the ever-evolving angioarchitecture and hemodynamic proﬁle of these lesions. Despite these challenges,certain fundamental principles have been established as our understanding of the pathogenesis, natural history,hemodynamics,and treatment outcomes has expanded and evolved over the last few decades.These principles are crucial to adhere to in the overall management of these lesions and are highlighted and expanded upon herein.(J Vasc Surg2015;62:1667-76.)In a seminal article,Mulliken and Glowacki1provided appropriate histologic distinction between hemangiomas and vascular malformations(VMs).Hemangiomas were found to be generally benign vascular tumors of endothelial cell origin with speciﬁc antigenic proﬁle,tumor markers, and clinical behavior patterns depending on the type of hemangioma2,3(Table I).Vascular malformations,on the other hand,do not arise from a neoplastic process, but are rather caused by developmental errors during vas-culogenesis.4-7This important histologic distinction was adopted by the International Society for Study of Vascular Anomalies(ISSVA)and further expanded upon to formu-late a clinically oriented classiﬁcation scheme(Table I).The ISSVA classiﬁcation categorizes vascular malformations primarily based on their hemodynamics andﬂow proper-ties.As such,they are broken down into slow-ﬂow venous and lymphatic malformations,high-ﬂow arteriovenous malformations(AVMs),and congenital mixed syndromes (Figs1and2).VMs can occur as simple isolated lesions or in combination with other bined malformations are more commonly encountered when part of a syndrome(Table I).The Hamburg classiﬁcation represents another fre-quently used organization scheme preferred by some clini-cians with an emphasis on the proposed embryogenesis of VMs and their anatomic relationship with major named vascular trunks.2,5With a stronger emphasis on the clinical and hemodynamic proﬁle of VMs,the ISSVA classiﬁcation has a broader day-to-day clinical applicability and is preferred by most experts in theﬁeld.It will be the classi-ﬁcation scheme referenced in this article,which focuses on general diagnostic and therapeutic principles involved in management of high-ﬂow peripheral AVMs. PREVALENCE AND PATHOPHYSIOLOGY AVMs represent pathologic connections between arteries and veins anywhere upstream of capillary level. Congenital AVMs are rarer than their acquired and slow-ﬂow counterparts,although the true prevalence remains elusive and roughly estimated according to autopsy and population-based studies(approximately1per100,000 person-years with>50%involving the head and neck).8-10 Congenital AVMs occur most often spontaneously andFrom the Vascular Anomalies&Malformations Program(VAMP)at theDivision of Vascular Surgery,Department of Surgery,Rutgers RobertWood Johnson Medical School,Robert Wood Johnson University Hos-pital,Bristol-Myers Squibb Children’s Hospital a;and the Rutgers RobertWood Johnson Medical School.bAuthor conﬂict of interest:none.Correspondence:Naiem Nassiri,MD,Assistant Professor,Vascular Surgery,Department of Surgery,Division of Vascular Surgery,Director,VascularAnomalies&Malformations Program(VAMP),Rutgers Robert WoodJohnson Medical School,Robert Wood Johnson University Hospital,Bristol-Myers Squibb Children’s Hospital,One Robert Wood JohnsonPlace,MEB541,New Brunswick,NJ08901(e-mail:nn207@rutgers.edu).The editors and reviewers of this article have no relevantﬁnancial relationshipsto disclose per the JVS policy that requires reviewers to decline review of anymanuscript for which they may have a conﬂict of interest.0741-5214CopyrightÓ2015by the Society for Vascular Surgery.Published byElsevier Inc./10.1016/j.jvs.2015.08.0521667less commonly as part of a broader syndrome such as Parkes-Weber syndrome,phosphatase and tensin homolog hamartoma syndrome,Osler-Weber-Rendu(OWR)syn-drome,and congenital lipomatous overgrowth,vascular malformations,epidermal nevi,and skeletal deformities (CLOVES)syndrome.Most of these syndromes are sec-ondary to sporadic gene mutations although a few are inheritable(ie,OWR).6,11-14Recently,an association has been made between AVMs and a constitutively active form of NOTCH-4,a signaling protein involved in endothelial cell differentiation during vasculogenesis and-angiogenesis.15-18Moreover,upstream manipulation of NOTCH-4expression has been associated with AVM regression and formation of higher resistance capil-laries.16,19These newly discovered biomolecular pathways can serve as potential therapeutic targets for treatment of both sporadic and syndromic AVMs.Although AVMs are congenital lesions,symptoms do not develop until the lesion grows large enough to cause hemodynamic disturbance.1,20,21Growth can be triggered by environmental factors such as activity,trauma,and/or changes in the hormonal milieu as occurs during puberty and pregnancy.6,22,23Symptomatology is greatly variable and largely dependent on location and extent of the AVM.The extremities are the most common anatomic distribution outside the head and neck,followed by the pelvis and the viscerum.9Upper and lower extremities are affected equally and there is no sex predilection for sporadic AVMs.9,22Natural history,expected symptomatology,and indications for treatment can vary based on location and size of the lesion.CLINICAL PRESENTATION AND PHYSICAL EXAMINATION FINDINGSPhysical examination can be limited by the accessibility of the AVM.Pulse examination can be highly variable. Most superﬁcial,accessible lesions present as a com-pressible mass(Fig1).A palpable thrill may be present. Handheld Doppler interrogation can be a reliable and consistently reproducible measure for rapid assessment of the quality and quantity ofﬂow through the lesion.Widespread,long-standing lesions may have much more prominent physical examinationﬁndings,including dilated,tortuous,and often aneurysmal draining veins, lipodermatosclerosis,edema,lymphedema,and rarely signs and symptoms of cardiac overload.Neurosensory def-icits and acral tissue loss may be present in severe cases.In-ternal and visceral AVMs are much more difﬁcult to detect based on physical examination alone.Audible bruits may not always be present.A detailed history combined with precise imaging,therefore,become essential for accurate diagnosis.9,11,24The earliest clinical manifestation particularly when the extremities are involved is the presence of venous hyperten-sion,which can cause aneurysmal degeneration of draining veins,axial reﬂux,edema,and chronic inﬂammatory changes.9,14,25-27Arterial steal resulting in acral tissue loss is a later manifestation of larger,more widespread AVMs and is exacerbated by the preceding venous hyperten-sion.11,14,22,25,27A high-output cardiac state with subse-quent cardiopulmonary overload is a rare occurrence with extremity AVMs(<1%of cases)but can potentially develop in extensive,widespread cases.9In the absence of overt symptoms,focal isolated extremity AVMs can be observed safely.Close clinical follow-up and patient education is important under these circumstances.28Larger,more extensive lesions and those accompanied by symptoms require more urgent angiographic evaluation to assess the angioarchitecture and to evaluate for angioembolization, which is often performed in a coordinated,staged fashion.Most internal and visceral lesions are asymptomatic or associated with vague,general symptoms such as aches and pain,throb,and bleeding diathesis depending on the location and size of the lesion.While a high-output cardiac state remains a rare occurrence in these locations, occurring in fewer than1%of peripheral AVMs,9,27an exception to this rule involves AVMs in low-resistanceTable I.Updated2014International Society for Study of Vascular Anomalies(ISSVA)Classiﬁcation for Vascular AnomaliesVascular tumorsBenignInfantile hemangiomaCongenital hemangiomaRapidly involutingNoninvolutingLocally aggressiveKaposiform hemangioendotheliomaMalignantAngiosarcomaKaposi sarcomaVascular MalformationsSimple isolated lesionsSlowﬂowLymphatic malformationsVenous malformationsCapillary malformationsHighﬂowAVMs andﬁstulasCombined lesionsLymphovenous malformationsCapillary venous malformationsCapillary lymphatic malformationsCapillary AVMsCongenital syndromesKlippel-Trenaunay syndromeParkes Weber syndromeOWR/hereditary hemorrhagic telangiectasiaCLOVES syndromeProteus syndromePTEN hamartomaBannyan-Riley-RuvalcabaCowden syndromeMaffucci syndromeBlue rubber bleb nevus syndromeSturge-Weber syndromeAVM,Arteriovenous malformation;CLOVES,congenital lipomatous overgrowth,vascular malformations,epidermal nevi,and skeletal/spinal deformities;OWR,Osler-Weber-Rendu;PTEN,phosphatase and tensin homolog.JOURNAL OF VASCULAR SURGERY1668Nassiri et al December2015vascular beds such as the renal circulation.29Renal AVMs have a more direct,ﬁstulous arteriovenous connection and almost always require treatment regardless of the severity of symptoms given the morbidity associated with persistent growth and paradoxic embolization.29Renovas-cular hypertension,pain,hematuria,abdominal or ﬂank bruit,and cardiopulmonary overload are typical features of most congenital renal AVMs.29The presence of a pulmonary AVM should raise the suspicion for OWR syndrome as 80%of pulmonary AVMs are associated with this syndrome (Fig 2).12,30-32Nearly all require treatment at the time of detection,although ﬁstulas $3mm in diameter have had a stronger association with paradoxic embolization in a few retrospec-tive series.12,30,31Physical exam ﬁndings are often subtle but can include pulmonary bruit,cyanosis,clubbing,and hypoxemia.Depending on the location and size of the lesion,rare but serious complications such as hemoptysis,hemothorax,congestive heart failure,palpitations,and par-adoxic intracerebral embolization can be present and have been reported with variable incidence in the literature.30,32Visceral AVMs can occur anywhere along the alimentarytract.9Examples include oral mucosal telangiectasias in OWR syndrome and colonic angiodysplasias.33Associated gastrointestinal bleeding can range from slow ooze to massive,life-threatening hemorrhage depending on the size,location,and chronicity of the lesion.9Portal venous hypertension,ascites,and variceal bleeding can also accom-pany larger,more widespread lesions.9,26,34-36IMAGINGDuplex ultrasonography can be an adequate initial screening modality for more focal,super ﬁcial AVMs.24B-mode imaging and color-ﬂow Doppler characteristically reveal a hypervascular network of dilated,tortuous channels including multiple arterial feeders and venous drainers.The latter may at times undergo aneurysmal degeneration as a result of long-standing arterialization of the venous system.Spectral waveform analysis reveals a high-ﬂow,low-resistance vascular bed.De ﬁnitive diagnosis,however,is often made via contrast-enhanced magnetic resonance imaging.9,25,28AVMs characteristically feature moderate T2enhancement with interspersed ﬂow voids which represent foci of high-ﬂow shunting within the lesion (Figs 1and 3).MagneticFig 1.A,Isolated high-ﬂow arteriovenous malformation (AVM)of the right hypothenar region.B,Arteriogram re-veals prominent palmar arch nidus fed by the radial artery with decreased distal digital ﬂow.C,Transvenous coil embolization of venous drainage was performed (note guidewire in distal cephalic vein and anchored detachable coil (white arrow )deposited in nidus venous drainage tract.This was followed by transarterial and direct percutaneous nidus embolization using Onyx.Note Onyx deposit cast in completion angiogram (white arrowhead ).There is signi ﬁcant improvement in distal digital ﬂow with no evidence of nontarget embolization.D,Asymmetric,compressible soft tissue masses along anterolateral leg in Cowden syndrome suspicious for AVMs.E,Note moderate T2enhancement on magnetic resonance imaging with scattered ﬂow-void foci.JOURNAL OF VASCULAR SURGERY Volume 62,Number 6Nassiri et al 1669resonance angiography and/or computed tomography angi-ography can be helpful adjunctive modalities for delineation of the angioarchitecture of the AVM particularly when plan-ning an intervention.9,28,37-39The gold standard imaging modality,however,remains catheter-directed angiography.Characteristic angiographic features include enlarged,dilated,often tortuous arterial in ﬂow into an intervening nidus of various con ﬁgurations with prompt shunting into dilated,occasionally aneurysmal draining veins.9Renal and pulmonary AVMs tend to lack this intervening nidus and have a more direct,ﬁstulous arteriovenous connection.9,32TREATMENTIndications for AVM treatment vary based on size,loca-tion,and symptom severity.9,25,28,40-44Focal,asymptomatic AVMs affecting the trunk and extremities can be observed safely with regular clinical follow-up after initial magnetic resonance imaging con ﬁrms the extent and con ﬁguration of the lesion.Patient compliance with regular interval follow-up d generally at 3-,6-,and 12-month intervals and annually thereafter if lesion remains quiescent d is empha-sized.Repeat imaging and/or angiographic interrogation is reserved generally for situations warranting more urgent therapy or in case of any changes in local or systemic hemody-namics,development of symptoms,or interval growth of lesion.Most peripheral AVMs,particularly those involving the extremities,pelvis,and viscerum,characteristically feature a nidus interpositioned between the feeding arteries and the draining veins (Figs 1,2,4,and 5).This nidus is a convoluted network of densely packed,tortuous,poorly differentiated blood vessels with an extremely low-resistancevascularFig 2.A and B,Scattered erythematous macules (telangiectasias)along volar digital and tongue distribution.C,Computed tomography angiography reveals a pelvic arteriovenous malformation (AVM)fed by the left ovarian artery.Findings strongly suggestive of Osler-Weber-Rendu (OWR)syndrome.D,Transarterial access into the AVM nidus was not possible given the extreme tortuosity of the feeding artery.Therefore,retrograde transvenous access was attempted.Note (D)extremely tortuous,elongated left ovarian artery feeding an AVM nidus with (E)subsequent shunting into an aneurysmal draining ovarian vein on delayed arterial phase runs.F,Retrograde,transvenous access is achieved via coaxial microcatheter system via the left renal vein with (G)nidus embolization using detachable coils and Onyx.H,Completion angiogram shows complete obliteration of the AVM with no evidence of nontarget embolization.JOURNAL OF VASCULAR SURGERY1670Nassiri et alDecember 2015tone (Figs 1,2,4,and 5).9,25,28It can act as a low-pressure sump,aggressively recruiting collateral in ﬂow and promot-ing angiogenesis.9,27Without adequate nidus penetration,proximal occlusion techniques such as surgical ligation,clipping,coil embolization,and covered stent exclusion of AVMs are futile endeavors,despite impressive initial results.9,25,28New collateral feeders will inevitably develop to continuously supply the low-resistance nidus bed.9The main goal of AVM therapy,therefore,is nidus in ﬁltration as a means of increasing distal transcapillary ﬂow and eliminating arterialization of the venous system.Nidus access is best achieved via development of a coaxial,microcatheter system for superselective delivery of liquid embolic agents that penetrate and thrombose the nidus (Figs 1,2,4,and 5).9Not all AVMs,however,feature a nidus.As mentioned earlier,those involving the pulmonary and renal circulation have a more direct ﬁstulous connection.Proximal occlusive devices such as coils and plugs can be curative in these speci ﬁc locations.12,28,30,45Operative intervention plays a limited role in high-ﬂow AVM treatment.9,26-28,40,46,47It is best reserved for exci-sion of focal,isolated,super ﬁcial lesions or as an adjunctive modality after embolization of exophytic,dis ﬁguring lesions.9,26-28,40,46,47The latter approach requires a multi-disciplinary strategy for adequate excision and subsequent reconstruction.26,28AVM nidus access can be performed via transarterial,transvenous,or direct puncture routes (Figs 1,2,4,and 5).9,48,49Sometimes,a combination of these approaches may be necessary (Fig 1).Although transarterial access is the most common and straightforward,it may not always be achievable owing to extreme tortuosity of feeding ves-sels,vasospasm,and innumerable arterial feeders (Figs 2and 4).Under these circumstances,the transvenous route is another viable option for nidus penetration that is gain-ing popularity and has proven technically successful.9,49-53The use of liquid embolic agents via the transvenous route is technically challenging given directionality of blood ﬂow.48,49This may require adjunctive,ﬂow-limiting tech-niques such as balloon-facilitated out ﬂow and/or in ﬂow control,and deliberate use of polymerizing embolic agents so as to minimize nontarget embolization.9,48,49,51-53Direct,percutaneous access into the AVM nidus is another viable option that can be used alone or in conjunction with other techniques (Figs 1and 5).9The location of the nidus plays an important role in determining the feasibility of this option and is not always possible.Transarterial road map guidance is always required with this technique and famil-iarity with the polymerization properties of the embolic agent used is crucial for successful delivery and avoidance of disastrous complications associated with nontarget embolization and extravasation.9,27There are no absolute contraindications to AVM ther-apy.Relative contraindications depend on the treatment modality and the embolic agent used.By far the most important relative contraindication is a lack of experience and expertise with AVM treatment.Each embolic agent has its own unique set of advantages and disadvantages,which one must be familiar with before treatment.Other relative contraindications include known allergic reactions to the embolic agent,previous complications from embolo-therapy,and inadequate nidus access.LIQUID EMBOLIC AGENTSA variety of different liquid embolic agents exist d some off-label d for use within the peripheral circulation,each with its own unique advantages,risks,andtechnicalFig 3.Contrast-enhanced,cross sectional fat suppressed T2magnetic resonance imaging demonstrating characteristic features differentiating (A)slow-ﬂow venous malformations from (B)high-ﬂow arteriovenous malformations (AVMs).A,Note T2-hyperintensity without ﬂow voids.B,Note mild to moderate peripheral T2enhancement with interspersed ﬂow voids suggestive of high-ﬂow shunts.(A,Courtesy of Dr Orhan Konez,MD;available at:/MRI.htm .)JOURNAL OF VASCULAR SURGERY Volume 62,Number 6Nassiri et al 1671idiosyncrasies.9,11,22,25,40,46,49,54Experience with tech-nique and familiarity with the embolic agents available and their respective nuances in various vascular beds can be important determinants of clinical outcome.9,22,25The agents most commonly used for peripheral AVM emboliza-tion nidus in ﬁltration include particulate agents (such as Embosphere Microspheres;Merit Medical,Systems,Inc,South Jordan,Utah),absolute ethanol (most effective but highly toxic),n -butyl cyanoacrylate (n-BCA;Tru-ﬁll;Cordis Neurovascular Inc,Fremont Calif;rapidly polymer-izing adhesive agent),and ethylene-vinyl alcohol copol-ymer (Onyx;ev3,Irvine,Calif;slowly polymerizing nonadhesive agent;available in various viscosity formula-tions).9,14,22,25These agents are discussed in more depth.Particulate agents.These agents are exempli ﬁed by microspheres and are highly effective embolic agents for treatment of hypervascular tumors,acute hemorrhagic episodes,and prophylactic embolization before planned surgical excision of hypervascular lesions.9Unlike poly-merizing embolic agents,microspheres play a limited role in AVM embolization given lack of adequate control over conformation to nidus con ﬁguration.A variety of sizes are available ranging from 300to 1200microns in microsphere diameter.If sized too large,they fail to provide adequate nidus penetration and are prone to recanalization and recurrence,despite impressive initial angiographic results.If sized too small,they fail to adequately occlude the nidus and can potentially lead to nontarget embolization.For these reasons,the current authors avoid using particulate agents in high-ﬂow AVM treatment.Polymerizing agents.These include n-BCA and Onyx and are delivered superselectively via the transarterialroute into the AVM nidus through a coaxial,microcatheter system.Alternatively,nidus delivery via direct stick emboli-zation and/or retrograde,transvenous approach are also achievable depending on the angioarchitecture of the AVM.9,48-50n-BCA is an acrylic adhesive that rapidly polymerizes and expands via an exothermic reaction when exposed to an ionic medium such as blood,thereby forming an almost instantaneous cast.The polymerization rate can be pro-longed by the addition of iodized ethyl esters (Lipiodol;Guerbet USA,Bloomington Ind),which can allow for more distal penetration of n-BCA.It also renders the mixture radiopaque for the purposes of ﬂuoroscopic moni-toring during delivery.During preparation of the mixture,care must be taken to avoid exposure of n-BCA to ionic media such as blood,saline,and contrast.The delivery sys-tem should be ﬂushed with D5W before injection so as to avoid premature polymerization and plugging of the deliv-ery system.By developing a coaxial delivery system,multi-ple microcatheter exchanges can be performed through a strategically located diagnostic catheter.This prevents plugging of the microcatheter and minimizes the risk of gluing the microcatheter tip in place.The latter complica-tion is more commonly reported in the neurointerventional literature given the smaller pro ﬁle of the coaxial delivery system used within that particular vascular bed.9,27Other major adverse reactions d such as nontarget embolization and premature polymerization d typically stem from inade-quate experience and lack of familiarity with technique and delivery.9Unlike,n-BCA,Onyx is a nonadhesive,slowly poly-merizing agent used in combination withdimethylFig 4.High-ﬂow AVM in the distal left leg.A and C,Note arterial feeders from the distal peroneal artery and posterior tibial artery feeding the nidus of the AVM with premature shunting into draining veins.B and D,Microcatheter access into the nidus of the AVM was performed with embolization of the nidus using Onyx.Note preservation and augmentation of distal out ﬂow and elimination of the nidus.JOURNAL OF VASCULAR SURGERY1672Nassiri et alDecember 2015sulfoxide.The latter is a solvent used to ﬂush the delivery system before Onyx injection so as to avoid premature polymerization.As a result,only dimethyl sulfoxide-compatible microcatheters d such as Direxion (Boston Scienti ﬁc,Marlborough,Mass),Rebar (ev3),Marathon (ev3)d can be used for Onyx infusion.Onyx is currently available in three different viscosity formulations d Onyx 18,Onyx 20,and Onyx 34.These three formulations can be used alone depending on the location,size,and resistance of the vascular bed treated or in combination with one another to provide more distal penetration of the AVM nidus without risking retrograde nontarget embolization.The technique of Onyx delivery is unique in that an initial plug is often formed around distal tip of microcatheter by injecting higher viscosity Onyx slowly via “gentle taps ”on the delivery syringe.This step requires patience and caution so as to avoid excessive (>1cm)retrograde ﬂow around microcatheter tip,which can make microcatheter retrieval dif ﬁcult and risks distal tip fracture during withdrawal.Once the plug is formed,however,the same or lower viscosity Onyx can be “pushed forward ”more rapidly to conform to and plug the AVM nidus.49Contin-uous ﬂuoroscopic monitoring is crucial.Given its slow poly-merization time,Onyx allows for a more controlled embolization with the ability to stop and restart delivery depending on ﬂow patterns during ﬂuoroscopic monitoring.This does,however,lead to signi ﬁcantly longer proceduretimes and greater radiation exposure.9,55The use of Onyx in super ﬁcially located AVMs is typically avoided given reports of permanent skin pigmentation and local ulcera-tion.56We have been able to avoid these complications by plugging the needle entry tracts during direct stick Onyx embolization with Surgi ﬂo collagen matrix (Ethicon,Somerville,NJ).Liquid sclerosing agents.Absolute ethanol is argu-ably the most effective and toxic embolic agent used in treatment of AVMs.9,25,28,41-44As a sclerosing agent,it denatures proteins and causes direct endothelial damage and thrombosis of the AVM nidus upon injection.Popu-larized by Yakes,it has evolved into one of the most widely used embolic agents for treatment of high-ﬂow AVMs.9,25,57-62It does,however,pose signi ﬁcantly higher risk compared with the other available agents dis-cussed.Reported adverse reactions include nerve injury,skin ulceration,and lethal central cardiopulmonary com-plications.9,25,41-44,56-65The potential for these adverse reactions is augmented by lack of radiopacity as addition of contrast renders the mixture less effective.9,11A maximum dose of 1mL/kg is used per session so as to avoid he-molysis,acute kidney injury,hemodynamic collapse,and sudden death.9,25Some authors have advocated for the routine use of a Swan-Ganz catheter during treatment as a result of these complications.9,25The use of ethanol for embolization of high-ﬂow AVMs should be restrictedtoFig 5.Isolated high-ﬂow AVM of the right foot fed by numerous branches of the dorsalis pedis artery (A).Given the extensive network of arterial feeders that would make catheterization of each and every one extremely arduous and time consuming,direct stick embolization of the nidus was performed using a micropuncture needle and injection of Onyx.Onyx cast at multiple nidus foci can be appreciated (B).Completion angiogram shows signi ﬁcant reduction of ﬂow through the nidus while preserving distal digital ﬂow (C).JOURNAL OF VASCULAR SURGERY Volume 62,Number 6Nassiri et al 1673those with extensive experience and expertise with this agent and its high risk proﬁle.MECHANICAL OCCLUSIVE DEVICESThe use of mechanical occlusive devices such as plugs and coils in the treatment of high-ﬂow AVMs is restricted to those situations where there exists a direct,ﬁstulous connection between the artery and vein without an inter-vening nidus,such as those which occur in the renal and pulmonary circulations.29Alternatively,these devices may provide a scaffold upon which further embolization via liquid embolic agents can be performed,thereby decreasing the volume of embolic agent needed to shut down the AVM.26,48They can also be deployed asﬂow rate control adjunctive modalities typically within aneu-rysmal draining veins so as to minimize risk of nontarget embolization of liquid embolic agents during transarterial or direct access delivery.29OUTCOMESGiven rarity of peripheral AVMs,variability in thera-peutic modalities of choice,diversity of embolothera-peutic options,and absence of reporting standards,the evaluation and analysis of treatment outcomes is difﬁ-cult.26,28,40,46,66,67The literature remains limited to case reports and retrospective case series mostly from a few cen-ters of excellence that employ a multidisciplinary approach to management of these complicated lesions.28,68Despite these limitations,some general trends are encountered.It is recommended that AVM treatment should be restricted to those with adequate experience and expertise within the framework of a multidisciplinary,dedicated center of excel-lence.28With the rare exception of readily accessible,focal, isolated lesions,transcatheter embolization provides the ﬁrst-line and often sole therapeutic modality.Choice of embolic agent remains at the discretion of the treating interventionalist and should be based on experience and expertise.No agent has proven superior to others.In fact,a variety of different embolic agents may be used at times for optimal results.26,66In general,in experienced hands,the technical success rate deﬁned as successful delivery of embolic agent into AVM nidus has been approximately80%and reported as high as100%in some small series.9,25,26,28,40-44,46,57-62,66,67,69Cure is achieved in 10%or fewer of cases.9,25,26,28,40-44,46,57-62,66,67,69Between 40%and80%of patients report improvement in symptoms after successful embolization.9,25,26,28,40,42-44,46,57-62,66,67,69 However,recurrence is common(as high as50%)particu-larly in diffuse AVMs affecting the extremities.41-44,46,67,69 Recurrence can either be due to recanalization of pre-viously embolized lesions or continued expansion.Time to recurrence,therefore,remains greatly variable and unpre-dictable,despite successful treatment.Complication rates are also greatly variable,depending on the location and extent of the AVM and embolic agent used.41,41-44,46,54,67,69Although highly effective,ethanol is by far the most toxic embolic agent available with compli-cation rates as high as65%in some series.56-65SUMMARYCongenital high-ﬂow AVMs are pathologic connec-tions between arteries and veins anywhere upstream of capillary level.These can either be direct,ﬁstulous con-nections or,more commonly,contain an intervening nidus d a convoluted network of blood vessels with poorly differentiated endothelial cells.Natural history and symp-tomatology largely depend on extent and location of the lesion.Venous hypertension as a result of chronic arterial-ization of the draining veins is a major source of early morbidity.Distal ischemia is a later manifestation.Endo-vascular treatment has evolved into a mainstay of treat-ment.Although direct arteriovenousﬁstulas can be cured by use of proximal occluding devices,AVMs with a nidus require inﬁltration with a liquid embolic agent delivered superselectively via a coaxial,microcatheter-based system.Without this,all attempts at more proximal inﬂow control are futile.Given their convoluted and evolving angioarchitecture,AVMs readily render them-selves to creativity and technical innovation during treat-ment.Experience and expertise with various therapeutic modalities remain the most important determinants of clinical outcomes.AUTHOR CONTRIBUTIONSConception and design:NNAnalysis and interpretation:NNData collection:NN,NC,JTWriting the article:NN,NC,JTCritical revision of the article:NNFinal approval of the article:NNStatistical analysis:Not applicableObtained funding:Not applicableOverall responsibility:NNREFERENCES1.Mulliken JB,Glowacki J,Thomson HG.Hemangiomas and vascularmalformations in infants and children:a classiﬁcation based on endo-thelial characteristics.Plast Reconstr Surg1982;69:412-22.2.Lee BB,Laredo J,Lee TS,Huh S,Neville R.Terminology and clas-siﬁcation of congenital vascular malformations.Phlebol Venous Forum R Soc Med2007;22:249-52.3.ISSVA Classiﬁcation of Vascular Anomalies[Internet].InternationalSociety for the Study of Vascular Anomalies;2014.Available at:issva.org/classiﬁcation.Accessed July31,2015.4.Nassiri N,TMJ O,Rosen RJ,Moritz J,Waner M.Staged endovascularand surgical treatment of slow-ﬂow vulvar venous malformations.Am J Obstet Gynecol2013;208:366.e1-6.5.Lee BB,Baumgartner I,Berlien P,Bianchini G,Burrows P,Gloviczki P,et al.Guideline.Diagnosis and treatment of venous malformations.Consensus document of the International Union of 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确切的病史可为贫血的诊断提供重要线索，应全面、详尽而有重点地询问。
（1）贫血表现（2）致病因素（3）原发疾病（4）遗传因素（5）治疗反应
2.体格检查
（1）一般状况：患者的发育、营养、表情、血压及体温等（2）特殊体征：可为明确贫血性质提供重要依据（3）神经系统表现：触觉、位置和震颤感觉减退或消失，行动不便
致死性
并发症
脑血管意外（AVC）视网膜病急性胸痛综合征心腔扩大性心肥大结石肾功能不全假外科性疼痛脾扣留股骨坏死阴茎异常勃起 “手-足”综合征溃疡
鉴别诊断
DIFFERENTIAL DIAGNOSIS
贫血诊断三步曲
确认贫血的存在及其程度
了解贫血的形态学类型
落实贫血的病因学诊断
1.了解病史
TYPICAL CLINICAL MANIFESTATION AND DIFFERENTIAL DIAGNOSIS
典型临床表现及鉴别诊断
临床表现

早年发病患者多有生长和发育不良，一般状况较差，易发生感染 ,尤其是肺炎球菌性感染。心、肺功能常受损，可发生充血性心力衰竭。肾脏受累可表现为等渗尿血尿、多尿，部分患者发展为肾病综合征、肾功能衰竭。骨质疏松，导致脊柱变形呈双凹形或鱼嘴形股骨头无菌性坏死。眼部症状由视网膜梗死、眼底出血、视网膜脱离等病变引起。神经系统表现有脑血栓形成、蛛网膜下隙出血。男性患者可有性

简要定义：红细胞成球形，使膜脆性增加而引起溶
血性贫血相似体征：脾肿大，黄疸鉴别方法：通过直接coomb’s 试验（抗人球蛋白试验）
3.实验室检查

实验室检查是确定贫血的存在及其程度，明确贫血性质与病因的重要方法。
红细胞的镜下鉴别
镰状细胞筛查实验
阳性（箭头所指）和阴性（清亮）的实验结果对照
与海洋性贫血的鉴别

简要定义：先天性血红蛋白量的异常相似体征：脾肿大，黄疸鉴别方法：在酸性和碱性ＰＨ下进行血红蛋白
电泳

发炎时姆趾缩短

患者的红血球呈镰刀形或半月形，与正常的双凹盘状红血球不同。患者红血球的生命期较短，易造成患者贫血现象。患者镰刀型红血球细胞会使血流减缓并阻断小血管，因而使组织受损并发生疼痛现象。患者经常出现周期性的疼痛和急性胸部症候群，引起发烧和呼吸道症状，例如呼吸困难。寿命比正常人短（30岁以下）。