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Research Guides

Multiple Case Studies

Nadia Alqahtani and Pengtong Qu

Description

The case study approach is popular across disciplines in education, anthropology, sociology, psychology, medicine, law, and political science (Creswell, 2013). It is both a research method and a strategy (Creswell, 2013; Yin, 2017). In this type of research design, a case can be an individual, an event, or an entity, as determined by the research questions. There are two variants of the case study: the single-case study and the multiple-case study. The former design can be used to study and understand an unusual case, a critical case, a longitudinal case, or a revelatory case. On the other hand, a multiple-case study includes two or more cases or replications across the cases to investigate the same phenomena (Lewis-Beck, Bryman & Liao, 2003; Yin, 2017). …a multiple-case study includes two or more cases or replications across the cases to investigate the same phenomena

The difference between the single- and multiple-case study is the research design; however, they are within the same methodological framework (Yin, 2017). Multiple cases are selected so that “individual case studies either (a) predict similar results (a literal replication) or (b) predict contrasting results but for anticipatable reasons (a theoretical replication)” (p. 55). When the purpose of the study is to compare and replicate the findings, the multiple-case study produces more compelling evidence so that the study is considered more robust than the single-case study (Yin, 2017).

To write a multiple-case study, a summary of individual cases should be reported, and researchers need to draw cross-case conclusions and form a cross-case report (Yin, 2017). With evidence from multiple cases, researchers may have generalizable findings and develop theories (Lewis-Beck, Bryman & Liao, 2003).

Creswell, J. W. (2013). Qualitative inquiry and research design: Choosing among five approaches (3rd ed.). Los Angeles, CA: Sage.

Lewis-Beck, M., Bryman, A. E., & Liao, T. F. (2003). The Sage encyclopedia of social science research methods . Los Angeles, CA: Sage.

Yin, R. K. (2017). Case study research and applications: Design and methods . Los Angeles, CA: Sage.

Key Research Books and Articles on Multiple Case Study Methodology

Yin discusses how to decide if a case study should be used in research. Novice researchers can learn about research design, data collection, and data analysis of different types of case studies, as well as writing a case study report.

Chapter 2 introduces four major types of research design in case studies: holistic single-case design, embedded single-case design, holistic multiple-case design, and embedded multiple-case design. Novice researchers will learn about the definitions and characteristics of different designs. This chapter also teaches researchers how to examine and discuss the reliability and validity of the designs.

Creswell, J. W., & Poth, C. N. (2017). Qualitative inquiry and research design: Choosing among five approaches . Los Angeles, CA: Sage.

This book compares five different qualitative research designs: narrative research, phenomenology, grounded theory, ethnography, and case study. It compares the characteristics, data collection, data analysis and representation, validity, and writing-up procedures among five inquiry approaches using texts with tables. For each approach, the author introduced the definition, features, types, and procedures and contextualized these components in a study, which was conducted through the same method. Each chapter ends with a list of relevant readings of each inquiry approach.

This book invites readers to compare these five qualitative methods and see the value of each approach. Readers can consider which approach would serve for their research contexts and questions, as well as how to design their research and conduct the data analysis based on their choice of research method.

Günes, E., & Bahçivan, E. (2016). A multiple case study of preservice science teachers’ TPACK: Embedded in a comprehensive belief system. International Journal of Environmental and Science Education, 11 (15), 8040-8054.

In this article, the researchers showed the importance of using technological opportunities in improving the education process and how they enhanced the students’ learning in science education. The study examined the connection between “Technological Pedagogical Content Knowledge” (TPACK) and belief system in a science teaching context. The researchers used the multiple-case study to explore the effect of TPACK on the preservice science teachers’ (PST) beliefs on their TPACK level. The participants were three teachers with the low, medium, and high level of TPACK confidence. Content analysis was utilized to analyze the data, which were collected by individual semi-structured interviews with the participants about their lesson plans. The study first discussed each case, then compared features and relations across cases. The researchers found that there was a positive relationship between PST’s TPACK confidence and TPACK level; when PST had higher TPACK confidence, the participant had a higher competent TPACK level and vice versa.

Recent Dissertations Using Multiple Case Study Methodology

Milholland, E. S. (2015). A multiple case study of instructors utilizing Classroom Response Systems (CRS) to achieve pedagogical goals . Retrieved from ProQuest Dissertations & Theses Global. (Order Number 3706380)

The researcher of this study critiques the use of Classroom Responses Systems by five instructors who employed this program five years ago in their classrooms. The researcher conducted the multiple-case study methodology and categorized themes. He interviewed each instructor with questions about their initial pedagogical goals, the changes in pedagogy during teaching, and the teaching techniques individuals used while practicing the CRS. The researcher used the multiple-case study with five instructors. He found that all instructors changed their goals during employing CRS; they decided to reduce the time of lecturing and to spend more time engaging students in interactive activities. This study also demonstrated that CRS was useful for the instructors to achieve multiple learning goals; all the instructors provided examples of the positive aspect of implementing CRS in their classrooms.

Li, C. L. (2010). The emergence of fairy tale literacy: A multiple case study on promoting critical literacy of children through a juxtaposed reading of classic fairy tales and their contemporary disruptive variants . Retrieved from ProQuest Dissertations & Theses Global. (Order Number 3572104)

To explore how children’s development of critical literacy can be impacted by their reactions to fairy tales, the author conducted a multiple-case study with 4 cases, in which each child was a unit of analysis. Two Chinese immigrant children (a boy and a girl) and two American children (a boy and a girl) at the second or third grade were recruited in the study. The data were collected through interviews, discussions on fairy tales, and drawing pictures. The analysis was conducted within both individual cases and cross cases. Across four cases, the researcher found that the young children’s’ knowledge of traditional fairy tales was built upon mass-media based adaptations. The children believed that the representations on mass-media were the original stories, even though fairy tales are included in the elementary school curriculum. The author also found that introducing classic versions of fairy tales increased children’s knowledge in the genre’s origin, which would benefit their understanding of the genre. She argued that introducing fairy tales can be the first step to promote children’s development of critical literacy.

Asher, K. C. (2014). Mediating occupational socialization and occupational individuation in teacher education: A multiple case study of five elementary pre-service student teachers . Retrieved from ProQuest Dissertations & Theses Global. (Order Number 3671989)

This study portrayed five pre-service teachers’ teaching experience in their student teaching phase and explored how pre-service teachers mediate their occupational socialization with occupational individuation. The study used the multiple-case study design and recruited five pre-service teachers from a Midwestern university as five cases. Qualitative data were collected through interviews, classroom observations, and field notes. The author implemented the case study analysis and found five strategies that the participants used to mediate occupational socialization with occupational individuation. These strategies were: 1) hindering from practicing their beliefs, 2) mimicking the styles of supervising teachers, 3) teaching in the ways in alignment with school’s existing practice, 4) enacting their own ideas, and 5) integrating and balancing occupational socialization and occupational individuation. The study also provided recommendations and implications to policymakers and educators in teacher education so that pre-service teachers can be better supported.

Multiple Case Studies Copyright © 2019 by Nadia Alqahtani and Pengtong Qu is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License , except where otherwise noted.

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• What Is a Case Study? | Definition, Examples & Methods

What Is a Case Study? | Definition, Examples & Methods

Published on May 8, 2019 by Shona McCombes . Revised on November 20, 2023.

A case study is a detailed study of a specific subject, such as a person, group, place, event, organization, or phenomenon. Case studies are commonly used in social, educational, clinical, and business research.

A case study research design usually involves qualitative methods , but quantitative methods are sometimes also used. Case studies are good for describing , comparing, evaluating and understanding different aspects of a research problem .

Table of contents

When to do a case study, step 1: select a case, step 2: build a theoretical framework, step 3: collect your data, step 4: describe and analyze the case, other interesting articles.

A case study is an appropriate research design when you want to gain concrete, contextual, in-depth knowledge about a specific real-world subject. It allows you to explore the key characteristics, meanings, and implications of the case.

Case studies are often a good choice in a thesis or dissertation . They keep your project focused and manageable when you don’t have the time or resources to do large-scale research.

You might use just one complex case study where you explore a single subject in depth, or conduct multiple case studies to compare and illuminate different aspects of your research problem.

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Once you have developed your problem statement and research questions , you should be ready to choose the specific case that you want to focus on. A good case study should have the potential to:

• Provide new or unexpected insights into the subject
• Challenge or complicate existing assumptions and theories
• Propose practical courses of action to resolve a problem
• Open up new directions for future research

TipIf your research is more practical in nature and aims to simultaneously investigate an issue as you solve it, consider conducting action research instead.

Unlike quantitative or experimental research , a strong case study does not require a random or representative sample. In fact, case studies often deliberately focus on unusual, neglected, or outlying cases which may shed new light on the research problem.

Example of an outlying case studyIn the 1960s the town of Roseto, Pennsylvania was discovered to have extremely low rates of heart disease compared to the US average. It became an important case study for understanding previously neglected causes of heart disease.

However, you can also choose a more common or representative case to exemplify a particular category, experience or phenomenon.

Example of a representative case studyIn the 1920s, two sociologists used Muncie, Indiana as a case study of a typical American city that supposedly exemplified the changing culture of the US at the time.

While case studies focus more on concrete details than general theories, they should usually have some connection with theory in the field. This way the case study is not just an isolated description, but is integrated into existing knowledge about the topic. It might aim to:

• Exemplify a theory by showing how it explains the case under investigation
• Expand on a theory by uncovering new concepts and ideas that need to be incorporated
• Challenge a theory by exploring an outlier case that doesn’t fit with established assumptions

To ensure that your analysis of the case has a solid academic grounding, you should conduct a literature review of sources related to the topic and develop a theoretical framework . This means identifying key concepts and theories to guide your analysis and interpretation.

There are many different research methods you can use to collect data on your subject. Case studies tend to focus on qualitative data using methods such as interviews , observations , and analysis of primary and secondary sources (e.g., newspaper articles, photographs, official records). Sometimes a case study will also collect quantitative data.

Example of a mixed methods case studyFor a case study of a wind farm development in a rural area, you could collect quantitative data on employment rates and business revenue, collect qualitative data on local people’s perceptions and experiences, and analyze local and national media coverage of the development.

The aim is to gain as thorough an understanding as possible of the case and its context.

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In writing up the case study, you need to bring together all the relevant aspects to give as complete a picture as possible of the subject.

How you report your findings depends on the type of research you are doing. Some case studies are structured like a standard scientific paper or thesis , with separate sections or chapters for the methods , results and discussion .

Others are written in a more narrative style, aiming to explore the case from various angles and analyze its meanings and implications (for example, by using textual analysis or discourse analysis ).

In all cases, though, make sure to give contextual details about the case, connect it back to the literature and theory, and discuss how it fits into wider patterns or debates.

If you want to know more about statistics , methodology , or research bias , make sure to check out some of our other articles with explanations and examples.

• Normal distribution
• Degrees of freedom
• Null hypothesis
• Discourse analysis
• Control groups
• Mixed methods research
• Non-probability sampling
• Quantitative research
• Ecological validity

Research bias

• Rosenthal effect
• Implicit bias
• Cognitive bias
• Selection bias
• Negativity bias
• Status quo bias

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Home » Case Study – Methods, Examples and Guide

Case Study – Methods, Examples and Guide

Table of Contents

A case study is a research method that involves an in-depth examination and analysis of a particular phenomenon or case, such as an individual, organization, community, event, or situation.

It is a qualitative research approach that aims to provide a detailed and comprehensive understanding of the case being studied. Case studies typically involve multiple sources of data, including interviews, observations, documents, and artifacts, which are analyzed using various techniques, such as content analysis, thematic analysis, and grounded theory. The findings of a case study are often used to develop theories, inform policy or practice, or generate new research questions.

Types of Case Study

Types and Methods of Case Study are as follows:

Single-Case Study

A single-case study is an in-depth analysis of a single case. This type of case study is useful when the researcher wants to understand a specific phenomenon in detail.

For Example , A researcher might conduct a single-case study on a particular individual to understand their experiences with a particular health condition or a specific organization to explore their management practices. The researcher collects data from multiple sources, such as interviews, observations, and documents, and uses various techniques to analyze the data, such as content analysis or thematic analysis. The findings of a single-case study are often used to generate new research questions, develop theories, or inform policy or practice.

Multiple-Case Study

A multiple-case study involves the analysis of several cases that are similar in nature. This type of case study is useful when the researcher wants to identify similarities and differences between the cases.

For Example, a researcher might conduct a multiple-case study on several companies to explore the factors that contribute to their success or failure. The researcher collects data from each case, compares and contrasts the findings, and uses various techniques to analyze the data, such as comparative analysis or pattern-matching. The findings of a multiple-case study can be used to develop theories, inform policy or practice, or generate new research questions.

Exploratory Case Study

An exploratory case study is used to explore a new or understudied phenomenon. This type of case study is useful when the researcher wants to generate hypotheses or theories about the phenomenon.

For Example, a researcher might conduct an exploratory case study on a new technology to understand its potential impact on society. The researcher collects data from multiple sources, such as interviews, observations, and documents, and uses various techniques to analyze the data, such as grounded theory or content analysis. The findings of an exploratory case study can be used to generate new research questions, develop theories, or inform policy or practice.

Descriptive Case Study

A descriptive case study is used to describe a particular phenomenon in detail. This type of case study is useful when the researcher wants to provide a comprehensive account of the phenomenon.

For Example, a researcher might conduct a descriptive case study on a particular community to understand its social and economic characteristics. The researcher collects data from multiple sources, such as interviews, observations, and documents, and uses various techniques to analyze the data, such as content analysis or thematic analysis. The findings of a descriptive case study can be used to inform policy or practice or generate new research questions.

Instrumental Case Study

An instrumental case study is used to understand a particular phenomenon that is instrumental in achieving a particular goal. This type of case study is useful when the researcher wants to understand the role of the phenomenon in achieving the goal.

For Example, a researcher might conduct an instrumental case study on a particular policy to understand its impact on achieving a particular goal, such as reducing poverty. The researcher collects data from multiple sources, such as interviews, observations, and documents, and uses various techniques to analyze the data, such as content analysis or thematic analysis. The findings of an instrumental case study can be used to inform policy or practice or generate new research questions.

Case Study Data Collection Methods

Here are some common data collection methods for case studies:

Interviews involve asking questions to individuals who have knowledge or experience relevant to the case study. Interviews can be structured (where the same questions are asked to all participants) or unstructured (where the interviewer follows up on the responses with further questions). Interviews can be conducted in person, over the phone, or through video conferencing.

Observations

Observations involve watching and recording the behavior and activities of individuals or groups relevant to the case study. Observations can be participant (where the researcher actively participates in the activities) or non-participant (where the researcher observes from a distance). Observations can be recorded using notes, audio or video recordings, or photographs.

Documents can be used as a source of information for case studies. Documents can include reports, memos, emails, letters, and other written materials related to the case study. Documents can be collected from the case study participants or from public sources.

Surveys involve asking a set of questions to a sample of individuals relevant to the case study. Surveys can be administered in person, over the phone, through mail or email, or online. Surveys can be used to gather information on attitudes, opinions, or behaviors related to the case study.

Artifacts are physical objects relevant to the case study. Artifacts can include tools, equipment, products, or other objects that provide insights into the case study phenomenon.

How to conduct Case Study Research

Conducting a case study research involves several steps that need to be followed to ensure the quality and rigor of the study. Here are the steps to conduct case study research:

• Define the research questions: The first step in conducting a case study research is to define the research questions. The research questions should be specific, measurable, and relevant to the case study phenomenon under investigation.
• Select the case: The next step is to select the case or cases to be studied. The case should be relevant to the research questions and should provide rich and diverse data that can be used to answer the research questions.
• Collect data: Data can be collected using various methods, such as interviews, observations, documents, surveys, and artifacts. The data collection method should be selected based on the research questions and the nature of the case study phenomenon.
• Analyze the data: The data collected from the case study should be analyzed using various techniques, such as content analysis, thematic analysis, or grounded theory. The analysis should be guided by the research questions and should aim to provide insights and conclusions relevant to the research questions.
• Draw conclusions: The conclusions drawn from the case study should be based on the data analysis and should be relevant to the research questions. The conclusions should be supported by evidence and should be clearly stated.
• Validate the findings: The findings of the case study should be validated by reviewing the data and the analysis with participants or other experts in the field. This helps to ensure the validity and reliability of the findings.
• Write the report: The final step is to write the report of the case study research. The report should provide a clear description of the case study phenomenon, the research questions, the data collection methods, the data analysis, the findings, and the conclusions. The report should be written in a clear and concise manner and should follow the guidelines for academic writing.

Examples of Case Study

Here are some examples of case study research:

• The Hawthorne Studies : Conducted between 1924 and 1932, the Hawthorne Studies were a series of case studies conducted by Elton Mayo and his colleagues to examine the impact of work environment on employee productivity. The studies were conducted at the Hawthorne Works plant of the Western Electric Company in Chicago and included interviews, observations, and experiments.
• The Stanford Prison Experiment: Conducted in 1971, the Stanford Prison Experiment was a case study conducted by Philip Zimbardo to examine the psychological effects of power and authority. The study involved simulating a prison environment and assigning participants to the role of guards or prisoners. The study was controversial due to the ethical issues it raised.
• The Challenger Disaster: The Challenger Disaster was a case study conducted to examine the causes of the Space Shuttle Challenger explosion in 1986. The study included interviews, observations, and analysis of data to identify the technical, organizational, and cultural factors that contributed to the disaster.
• The Enron Scandal: The Enron Scandal was a case study conducted to examine the causes of the Enron Corporation’s bankruptcy in 2001. The study included interviews, analysis of financial data, and review of documents to identify the accounting practices, corporate culture, and ethical issues that led to the company’s downfall.
• The Fukushima Nuclear Disaster : The Fukushima Nuclear Disaster was a case study conducted to examine the causes of the nuclear accident that occurred at the Fukushima Daiichi Nuclear Power Plant in Japan in 2011. The study included interviews, analysis of data, and review of documents to identify the technical, organizational, and cultural factors that contributed to the disaster.

Application of Case Study

Case studies have a wide range of applications across various fields and industries. Here are some examples:

Business and Management

Case studies are widely used in business and management to examine real-life situations and develop problem-solving skills. Case studies can help students and professionals to develop a deep understanding of business concepts, theories, and best practices.

Case studies are used in healthcare to examine patient care, treatment options, and outcomes. Case studies can help healthcare professionals to develop critical thinking skills, diagnose complex medical conditions, and develop effective treatment plans.

Case studies are used in education to examine teaching and learning practices. Case studies can help educators to develop effective teaching strategies, evaluate student progress, and identify areas for improvement.

Social Sciences

Case studies are widely used in social sciences to examine human behavior, social phenomena, and cultural practices. Case studies can help researchers to develop theories, test hypotheses, and gain insights into complex social issues.

Law and Ethics

Case studies are used in law and ethics to examine legal and ethical dilemmas. Case studies can help lawyers, policymakers, and ethical professionals to develop critical thinking skills, analyze complex cases, and make informed decisions.

Purpose of Case Study

The purpose of a case study is to provide a detailed analysis of a specific phenomenon, issue, or problem in its real-life context. A case study is a qualitative research method that involves the in-depth exploration and analysis of a particular case, which can be an individual, group, organization, event, or community.

The primary purpose of a case study is to generate a comprehensive and nuanced understanding of the case, including its history, context, and dynamics. Case studies can help researchers to identify and examine the underlying factors, processes, and mechanisms that contribute to the case and its outcomes. This can help to develop a more accurate and detailed understanding of the case, which can inform future research, practice, or policy.

Case studies can also serve other purposes, including:

• Illustrating a theory or concept: Case studies can be used to illustrate and explain theoretical concepts and frameworks, providing concrete examples of how they can be applied in real-life situations.
• Developing hypotheses: Case studies can help to generate hypotheses about the causal relationships between different factors and outcomes, which can be tested through further research.
• Providing insight into complex issues: Case studies can provide insights into complex and multifaceted issues, which may be difficult to understand through other research methods.
• Informing practice or policy: Case studies can be used to inform practice or policy by identifying best practices, lessons learned, or areas for improvement.

Advantages of Case Study Research

There are several advantages of case study research, including:

• In-depth exploration: Case study research allows for a detailed exploration and analysis of a specific phenomenon, issue, or problem in its real-life context. This can provide a comprehensive understanding of the case and its dynamics, which may not be possible through other research methods.
• Rich data: Case study research can generate rich and detailed data, including qualitative data such as interviews, observations, and documents. This can provide a nuanced understanding of the case and its complexity.
• Holistic perspective: Case study research allows for a holistic perspective of the case, taking into account the various factors, processes, and mechanisms that contribute to the case and its outcomes. This can help to develop a more accurate and comprehensive understanding of the case.
• Theory development: Case study research can help to develop and refine theories and concepts by providing empirical evidence and concrete examples of how they can be applied in real-life situations.
• Practical application: Case study research can inform practice or policy by identifying best practices, lessons learned, or areas for improvement.
• Contextualization: Case study research takes into account the specific context in which the case is situated, which can help to understand how the case is influenced by the social, cultural, and historical factors of its environment.

Limitations of Case Study Research

There are several limitations of case study research, including:

• Limited generalizability : Case studies are typically focused on a single case or a small number of cases, which limits the generalizability of the findings. The unique characteristics of the case may not be applicable to other contexts or populations, which may limit the external validity of the research.
• Biased sampling: Case studies may rely on purposive or convenience sampling, which can introduce bias into the sample selection process. This may limit the representativeness of the sample and the generalizability of the findings.
• Subjectivity: Case studies rely on the interpretation of the researcher, which can introduce subjectivity into the analysis. The researcher’s own biases, assumptions, and perspectives may influence the findings, which may limit the objectivity of the research.
• Limited control: Case studies are typically conducted in naturalistic settings, which limits the control that the researcher has over the environment and the variables being studied. This may limit the ability to establish causal relationships between variables.
• Time-consuming: Case studies can be time-consuming to conduct, as they typically involve a detailed exploration and analysis of a specific case. This may limit the feasibility of conducting multiple case studies or conducting case studies in a timely manner.
• Resource-intensive: Case studies may require significant resources, including time, funding, and expertise. This may limit the ability of researchers to conduct case studies in resource-constrained settings.

About the author

Muhammad Hassan

Researcher, Academic Writer, Web developer

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Home > JCPS > Vol. 15 (2022) > No. 2

Journal of Counselor Preparation and Supervision

A systematic approach to multiple case study design in professional counseling and counselor education.

Charmayne R. Adams , University of Nebraska at Omaha Follow Casey A. Barrio Minton , University of Tennessee Follow Jennifer Hightower , Idaho State University Follow Ashley J. Blount , University of Nebraska at Omaha Follow

Document Type

Case study, multiple case study, qualitative research, research design, counseling

Subject Area

Counseling, Counselor Education, Higher Education Counseling, Mental Health Counseling, Rehabilitation Counseling, School Counseling

Case study research is a qualitative methodology that allows researchers to explore complex phenomena in a structured way, that is rigorous and provides an enormous amount of depth. Three scholars are credited with major contributions to the case study literature: Merriam (1998), Stake (1995/2006), and Yin (1994). The purpose of this paper is to explore case study design for use in the counseling profession. The authors provide instruction on the case study scholars, data collection, analysis, and reporting for both single and multiple case study research designs. Finally, implications for student counselors, counselor educators, and counseling professionals are provided.

Recommended Citation

Adams, C. R., Barrio Minton, C. A., Hightower, J., & Blount, A. J. (2022). A Systematic Approach to Multiple Case Study Design in Professional Counseling and Counselor Education. Journal of Counselor Preparation and Supervision, 15 (2). Retrieved from https://digitalcommons.sacredheart.edu/jcps/vol15/iss2/24

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A Case Study Progression to Multiple Myeloma

Mary ann yancey.

Medical Oncology Branch at the Center for Cancer Research at the National Cancer Institute of the National Institutes of Health in Bethesda, MD.

Adam J. Waxman

Ola landgren.

Multiple myeloma consistently is preceded by precursor states, which often are diagnosed incidentally in the laboratory. This case report illustrates the clinical dilemma of progression from precursor to full malignancy. The article also discusses future directions in management and research focusing on myelomagenesis.

Multiple myeloma, characterized by the clonal proliferation of plasma cells in the bone marrow, is the second most common hematologic malignancy, with more than 20,000 new cases diagnosed per year in the United States ( Laubach, Richardson, & Anderson, 2010 ). Typical clinical features include anemia, renal failure, hypercalcemia, and skeletal lytic lesions ( Kyle & Rajkumar, 2004 ) (see Table 1 ). Despite significant advances in treatment, multiple myeloma has high morbidity and mortality reflected by an overall length of survival of about four to seven years ( Kumar et al., 2008 , Turesson, Velez, Kristinsson, & Landgren, 2009 ).

Diagnostic Criteria for Multiple Myeloma and Precursor States

MGUS—monoclonal gammopathy of undetermined significance; MM—multiple myeloma; SMM—smoldering multiple myeloma

Note . From “Criteria for the Classification of Monoclonal Gammopathies, Multiple Myeloma and Related Disorders” by the International Myeloma Working Group, 2003 , British Journal of Haematology , 121, pp. 752–753. Copyright 2003 by John Wiley and Sons. All rights reserved. Adapted with permission.

Multiple myeloma has two precursor states: monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma. MGUS is asymptomatic and affects about 3% of Caucasians older than age 50. MGUS has a 1% average annual risk for progression to multiple myeloma or related lymphoproliferative malignancies ( Kyle et al., 2002 , 2007 ) (see Figure 1 ). Two independent studies showed that multiple myeloma consistently is preceded by MGUS ( Landgren et al., 2009 ; Weiss, Abadie, Verma, Howard, & Kuehl, 2009 ). Smoldering multiple myeloma is another asymptomatic precursor to multiple myeloma with a substantially higher annual risk of progression. Smoldering multiple myeloma is defined by a monoclonal-protein concentration of 3 g/dl or higher or 10% or higher bone marrow plasma cells in the absence of end-organ damage ( International Myeloma Working Group, 2003 ). To date, an estimated 3,000 smoldering multiple myeloma cases are diagnosed annually in the United States; however, the numbers likely are not reliable because of prior inconsistent diagnostic criteria and under diagnosis from the malignancy’s asymptomatic nature ( Rajkumar, Lacy, & Kyle, 2007 ). Based on retrospective data from the Mayo Clinic, the average annual risk of progression from smoldering multiple myeloma to multiple myeloma is 10% for the first five years following smoldering multiple myeloma diagnosis, decreasing to 3% annually for the following five years, and becoming the same 1% annual rate of progression as MGUS thereafter ( Kyle et al., 2007 ).

Note . From “Clinical Course and Prognosis of Smoldering (Asymptomatic) Multiple Myeloma,” by R.A. Kyle, E.D. Remstein, T.M. Therneau, A. Dispenzieri, P.J. Kurtin, J.M. Hodnefield, and S.V. Rajkumar, 2007, New England Journal of Medicine, 356 , p. 2582. Copyright 2007 by Massachusetts Medical Society. All rights reserved.

In the late 1990s, Mr. A, an otherwise healthy 65-year-old Caucasian man, underwent a regular health check-up. As part of the blood work, serum protein electrophoresis was conducted. During the work-up, a monoclonal protein was detected and confirmed with immunofixation electrophoresis. The monoclonal protein was defined as immunoglobulin-G kappa with a concentration of 1.25 g/dl; the quantitative uninvolved immunoglobulin levels all were found to be normal. In addition, the complete blood count revealed normal hemoglobin, calcium, and creatinine levels. Mr. A was diagnosed with MGUS. Given the features of the serum protein abnormalities, Mr. A was recommended to have annual follow-up appointments to monitor his blood work. For several years, his monoclonal-protein level stayed in the range of 1–2 g/dl and he did not have other laboratory abnormalities or symptoms.

In early 2009, Mr. A’s monoclonal-protein level increased to 3.2 g/dl. He underwent a bone marrow biopsy with immunohistochemistry (CD138, kappa and lambda stains). Results of the biopsy showed 30%–40% plasma cells with kappa light-chain restriction. In addition, flow cytometry of the bone marrow aspirate showed that more than 99% of the plasma cells were abnormal. Serum calcium and creatinine levels were within normal limits. Albumin level was 3.2 g/dl, and the beta-2-microglobulin level was 2.3 mg/L. Skeletal survey was negative for lytic lesions. Taken together, the observations changed Mr. A’s diagnosis from MGUS to smoldering multiple myeloma.

After diagnosis, Mr. A was monitored every two months and assessed with serum protein electrophoresis, immunofixation electrophoresis, and routine laboratory tests (including calcium, albumin, complete blood count, and creatinine). The monoclonal-protein concentration increased by 0.3–0.5 g/dl at each visit, whereas calcium levels gradually increased and hemoglobin gradually decreased, despite the absence of clear symptoms.

In late 2009, Mr. A reported diffuse back pain and unspecific weak pain from the pelvis, so magnetic resonance imaging was done to exclude spinal cord compression; the result was negative. An 18-F-fluoro-deoxy-2-glucose positron-emission tomography/computed tomography (18-FDG PET/CT) scan had been done in early 2009 when the monoclonal-protein levels started to increase; the examination showed suspicious lesions in the vertebrae, whereas the skeletal survey was negative. Another 18-FDG PET/CT scan was conducted to compare to the previously noted abnormalities in the vertebrae. The scan revealed low intensity focal lesions in the sacrum and left iliac bone consistent with lytic lesions; again, the skeletal survey was negative for lytic lesions. According to diagnostic criteria, either lytic lesions or “abnormal compression fractures of vertebrae” detected by skeletal survey qualify for a diagnosis of multiple myeloma ( International Myeloma Working Group, 2003 ). In the context of Mr. A’s increasingly abnormal laboratory values, increased focal lesions on PET/CT, and symptoms in the area of abnormality, he was interpreted biologically and clinically as having multiple myeloma. He then began treatment for multiple myeloma.

Progression to Multiple Myeloma

To date, predicting whether an individual patient with MGUS or smoldering multiple myeloma will ultimately progress to multiple myeloma is not possible. However, two schemas have been developed to help define patients at higher or lower than average risk of progression (see Tables 2 and ​ and3). 3 ). Using the results of serum-protein assays including quantity of monoclonal protein, type of immunoglobulin heavy chain, and serum-free light chain ratio, as well as percentage of bone marrow plasma cells by biopsy in smoldering multiple myeloma, the Mayo Clinic developed a scheme to stratify patients based on risk of progression to multiple myeloma ( Dispenzieri et al., 2008 ; Rajkumar et al., 2005 ). The Spanish Programa Para el Estudio de la Terapéutica en Hemopatía Maligna (Program for the Study of Therapy in Hematologic Malignancies) (PETHEMA) study group developed a risk stratifications scheme based primarily on the results of immunophenotyping by flow cytometry, which requires a bone marrow aspirate sample ( Perez-Persona et al., 2007 ). Mr. A was at the highest risk for progression to multiple myeloma by the PETHEMA scheme (95% or higher abnormal plasma cells and decreased uninvolved immunoglobulins) and intermediate risk for progression by the Mayo Clinic criteria (monoclonal protein 3 g/dl or higher, bone marrow plasma cells 10% or higher, but serum-free light chain ratio lower than 8).

Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma: Predictors of Progression

PETHEMA—Programa Para el Estudio de la Terapéutica en Hemopatía Maligna (Program for the Study of Therapy in Hematologic Malignancies)

Note . Based on information from Perez-Persona et al., 2007 ; Rajkumar et al., 2005 .

Smoldering Multiple Myeloma to Multiple Myeloma: Predictors of Progression at Five Years

Note . Based on information from Dispenzieri et al., 2008 ; Perez-Persona et al., 2007 .

Although no formal guidelines exist for evaluation and follow-up, the Mayo Clinic recommends follow-up at two- to three-month intervals for the first year with monitoring of monoclonal-protein levels, serum chemistry, complete blood count, and urine protein studies ( Blade, Dimopoulos, Rosinol, Rajkumar, & Kyle, 2010 ). After that time, follow-up intervals may be extended to up to six months and maintained or reduced based on the patient’s risk profile. Because of the heterogeneous prognosis, thoughtful patient education is critical at all visits.

Outside of clinical trials, patients with smoldering multiple myeloma should not be treated unless progression to multiple myeloma occurs ( Kyle et al., 2007 ). Current guidelines do not endorse treatment of patients with smoldering multiple myeloma ( Kyle et al., 2007 ). In fact, prior clinical trials have not shown an increase in overall survival for patients with smoldering multiple myeloma treated with melphalan-prednisone, thalidomide, or bisphosonates, but zolendronate therapy decreased the risk of pathologic fractures following progression ( Barlogie et al., 2008 ; Hjorth et al., 1993 ; Musto et al., 2008 ). Preliminary data from an ongoing phase III trial using lenalidomide-dexamethasone versus observation in high-risk smoldering multiple myeloma has shown lower risk of progression for patients assigned to the treatment arm; overall survival data are not yet available ( Mateos et al., 2009 ). The goal of treating smoldering multiple myeloma is to cure the disease outright or to manage it chronically, delaying progression to full myeloma and improving survival. However, clinicians should consider the possibilities of significant drug toxicities, development of refractory disease, and long-term adverse events in asymptomatic patients ( Waxman, Kuehl, Balakumaran, Weiss, & Landgren , in press).

Multiple myeloma is a diagnosis based on clinical, laboratory, and radiographic assessment for myeloma-related end-organ damage. In contrast, MGUS and smoldering multiple myeloma often are incidental laboratory diagnoses based on presence and size of the monoclonal protein and percentage of bone marrow plasma cells. Current criteria for the diagnosis of MGUS, smoldering multiple myeloma, and multiple myeloma were developed by the International Myeloma Working Group in 2003. However, as in the case of Mr. A, the clinical picture can be highly complex, requiring very careful history and physical examination correlated with laboratory values and newer imaging studies.

Prospective molecular profiling studies are ongoing, with the expectation of gaining more accurate risk stratification for individuals with MGUS and smoldering multiple myeloma. Knowledge of present and future predictors of risk for progression may allow for better monitoring of patients with myeloma precursor disease. Future goals are to identify high-risk individuals and develop effective therapies with limited side effects aimed at delaying progression or cure in high-risk patients. At the National Institutes of Health in Bethesda, MD, ongoing studies focus on molecular profiling and the development of novel therapies for high-risk myeloma precursor disease. For more information, visit www.clinicaltrials.gov .

Acknowledgments

The authors take full responsibility for the content of the article. This work was supported by the Intramural Research Program of the National Cancer Institute of the National Institutes of Health. The content of this article has been reviewed to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the editorial staff.

Contributor Information

Mary Ann Yancey, Medical Oncology Branch at the Center for Cancer Research at the National Cancer Institute of the National Institutes of Health in Bethesda, MD.

Adam J. Waxman, Medical Oncology Branch at the Center for Cancer Research at the National Cancer Institute of the National Institutes of Health in Bethesda, MD.

Ola Landgren, Medical Oncology Branch at the Center for Cancer Research at the National Cancer Institute of the National Institutes of Health in Bethesda, MD.

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KYV-101 helps 2 hard-to-treat progressive MS patients: Case study

Treatment addresses 'one of the most difficult challenges in MS therapy'

by Steve Bryson, PhD | April 4, 2024

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Kyverna Therapeutics ‘ cell-based therapy KYV-101 had an acceptable safety profile and promising treatment effects when given to two people with hard-to-treat progressive multiple sclerosis (MS), according to a case study.

“We are very pleased about offering this potentially paradigm-shifting treatment opportunity to patients that have exhausted other medical recourses,” senior co-author Christoph Heesen, MD, professor for clinical and rehabilitative MS research at the University Medical Center Hamburg-Eppendorf, said in a Kyverna press release .

“Emerging findings indicating that this approach may affect disease biology in the central nervous system are promising, as preventing disease progression remains one of the most difficult challenges in MS therapy,” Heesen said. The central nervous system is comprised of the brain and spinal cord.

The case study, “ CD19-targeted chimeric antigen receptor T cell therapy in two patients with multiple sclerosis ,” was published in the journal Med .

MS is marked by immune-mediated damage to healthy parts of the spinal cord and brain. More than 20 therapies are approved for relapsing forms of MS , but far fewer options exist for people with progressive and nonactive disease forms of the disease.

Unraveling my ‘authentically human’ multiple sclerosis story

Targeting b-cells for elimination.

KYV-101 is designed to ease MS and other autoimmune conditions by eliminating B-cells, immune cells that generate self-reactive antibodies that mistakenly target healthy tissues and drive these disorders.

Treatment involves collecting a patient’s immune T-cells and modifying them in a lab to produce a chimeric antigen receptor (CAR) that selectively binds to CD19, a protein found at the surface of B-cells. Modified T-cells are then expanded in the lab and infused back into the patient with the goal of eliminating CD19-producing B-cells.

Researchers at Stanford University teamed up with Kyverna in March to conduct an investigator-initiated, open-label Phase 1 trial (NCT06138132) to test KYV-101 in as many as 12 people with primary progressive MS (PPMS) or secondary progressive MS (SPMS) who have not experienced recent relapses.

In January, the U.S. Food and Drug Administration (FDA) cleared the launch of an open-label, Phase 2 clinical trial called KYSA-7 to evaluate KYV-101 in a similar patient population.

Heesen and colleagues in Germany tested the feasibility and safety profile of KYV-101 in two patients with progressive MS. Both were treated as part of a named patient program, which allows treatment with unauthorized medicines in critically ill patients who fail to respond to conventional therapies.

The first case was a woman with a 23-year history of MS. She was initially diagnosed with relapsing-remitting MS (RRMS) and started taking Ocrevus (ocrelizumab) in 2021 due to progressive neurological deterioration. Despite receiving Fampyra (fampridine), sold in the U.S. as Ampyra , to address walking difficulty, her disease continued to worsen.

Within a few hours of KYV-101 infusion, she developed a recurring fever and was diagnosed with mild cytokine release syndrome (CRS), a large release of inflammatory molecules that can cause potentially life-threatening symptoms, for which she was treated. There were no signs of immune effector cell-associated neurotoxicity syndrome (ICANS), a potentially serious neurotoxic side effect associated with CAR-T cell therapies.

She experienced a temporary worsening of MS-related symptoms due to the fever, which eventually resolved. By day 100, her self-reported walking distance increased from 400 meters to 700 meters. Other neurological assessments remained unchanged.

Blood tests showed a peak expansion of CAR-T cells six and seven days after infusion, which remained detectable up to day 100, and B-cell counts were depleted by day 2. Treatment-related cells were also found in the cerebrospinal fluid (CSF), which surrounds the spinal cord and brain, and resulted in a drop in self-reactive antibodies.

Learning to walk for the umpteenth time with multiple sclerosis

Progressive ms patient’s disability remained stable.

The second case was a male patient diagnosed with PPMS in 2019 after a two-year history of worsening walking abilities and lesions on MRI scans. Despite treatment with Ocrevus, his walking disability worsened.

After the KYV-101 infusion, he showed no signs of CRS or ICANS over 28 days of follow-up, and no other adverse events were noted. No new lesions or neurological symptoms were observed, and his disability remained stable for one month after the infusion.

The patient showed only a modest expansion of CAR-T cells in blood and CSF, but B-cells, which were already undetectable during treatment with Ocrevus, remained so in the bloodstream. Antibody levels in the blood were reduced on day 14 post-infusion, but no changes in the levels of CSF self-reactive antibodies were noted.

“If safe administration can be replicated in other patients and efficacy be formally established in clinical trials, this may bring a relevant therapeutic option to patients with MS,” said senior co-author Nicolaus Kröger, MD, professor of clinical and rehabilitative MS research at the University Medical Center Hamburg-Eppendorf.

We are committed to transforming the standard treatment for patients living with multiple sclerosis.

The FDA granted fast-track status to KYV-101 as a potential treatment for progressive MS. Fast track designation is intended to advance the development of therapies that address the unmet medical needs of people with serious or life-threatening conditions.

KIV-101 also is being assessed in other autoimmune disorders, including lupus , myasthenia gravis , and systemic scleroderma .

“We are committed to transforming the standard of treatment for patients living with multiple sclerosis,” said Peter Maag, PhD, CEO of Kyverna. “The pioneering work done with KYV-101 by medical teams in Hamburg and in our trials in the U.S. helps build the data backbone needed to further advance our knowledge and hopefully accelerate development of CAR T-cell therapies in autoimmune diseases.”

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Multiple samples

Case study: the Spock consipracy trial

Sums of squares

Case study A: does diet affect longevity?

One-way anova model: generalization of two-sample, model details.

Data: \(Y_{ij}, 1 \leq i \leq n_j, j \in {\tt [lopro, N/N85, N/R40, N/R50, NP, R/R50]}\)

Model: \(Y_{ij} \sim N(\mu_j, \sigma^2)\) (Note: assumed equal variance here!)

Null: \(H_0\) no difference: \(\mu_{\tt lopro}=\dots=\mu_{\tt R/R50}\)

Alternative: \(H_a\) model holds for some values \(\mu_{\tt lopro},\dots,\mu_{\tt R/R50}\)

Fitting the model

Comparing the models, how much better a fit is model then model0 , extra sum of squares, \(f\) -statistic, convert “extra” sum of squares to unitless quantity, using anova, comparing two groups: n/n85 vs n/r50, confidence interval, comparing two groups: r/r50 vs n/r50, case study b: is the jury pool representative, any differences between judges, how about spock’s judge vs. others, how about variation only among others, summarizing all 3 models, some diagnostic plots, residual vs. fitted.

• Case Report
• Open access
• Published: 06 April 2024

Surgical management of multiple coronary artery to coronary sinus fistulas with giant left circumflex artery and multivalvular infective endocarditis

• Sang Bin Shin 1 ,
• Won Kyoun Park 2 ,
• Jae Won Choi 2 ,
• Jong Pil Jung 2 ,
• Chang Ryul Park 2 ,
• Yong Jik Lee 2 &
• Gwan Sic Kim   ORCID: orcid.org/0000-0002-0648-0178 2  

Journal of Cardiothoracic Surgery volume  19 , Article number:  186 ( 2024 ) Cite this article

Metrics details

Coronary artery fistula (CAF) is characterized as a congenital or acquired abnormal communication between a coronary artery and any of the four chambers of the heart (coronary–cameral fistula) or great vessels (coronary arteriovenous fistula) bypassing the capillaries within myocardium. CAF is a rare disease, challenging to diagnose and treat depending on the anatomical location and type of the fistula and accompanying diseases. This study aims to report a case with multiple coronary artery to coronary sinus (CS) fistulas with giant left circumflex artery and multivalvular infective endocarditis.

Peer Review reports

Introduction

CAF denotes a direct connection between coronary arteries and the heart chambers or great vessels. The drain flow through the fistula triggers a steal effect, diminishing capillary flow and heightening the risk of concurrent cardiac diseases. While asymptomatic cases discovered incidentally may warrant observation, patients diagnosed with other cardiac conditions—such as chronic ischemic damage, heart failure, aneurysmal changes, valve disease, or infective endocarditis—could benefit from corrective surgical intervention during procedures.

This study involves a 39-year-old male patient with no previous medical history who visited our hospital complaining of intermittent fever for 1 month. He had no history of recent overseas travel or invasive procedures, such as dental care or oriental acupuncture. The patient’s vital signs upon arrival were as follows: blood pressure 140/73 mmHg, regular heart rate 89 beats/min, respiratory rate 18 cycles/min, and body temperature 38.5℃. The laboratory test results indicated white blood cell count 8,410/mm 3 , hemoglobin 9.6 g/dl, total bilirubin 2.1 g/dl, C-reactive protein 4.59 mg/dl, and pro brain natriuretic peptide (pro BNP) 4,287 pg/mL. Conversely, other parameters were within normal limits. The chest radiographic findings showed a cardiothoracic (CT) ratio of 0.53, reflecting mild cardiomegaly. The electrocardiography indicated a normal sinus rhythm. The patient was initially admitted to the internal medicine department for evaluation of fever, and received empirical antibiotic treatment for 3 days before surgery. On the third day after admission, the transthoracic echocardiography (TTE) images indicated severe aortic regurgitation, severe mitral regurgitation, and moderate tricuspid regurgitation. Moreover, hyper-mobile vegetations of 3.0 × 1.2 cm 2 and 1.2 × 0.7 cm 2 in size were observed on aortic and mitral valves. The left and right ventricular sizes and systolic function were within normal limits. The report of the computerized tomography (CT) coronary angiogram exhibited that LCx was enlarged to an overall diameter of approximately 1.2 cm, and multiple left circumflex CAFs draining into CS were identified (Fig.  1 ). The patient was immediately referred to the cardiovascular and thoracic surgery department for surgery. On the account of the potential systemic embolic risk of hyper-mobile vegetations and progressing heart failure owing to multiple valve dysfunction, urgent surgery was performed with a diagnosis of multiple coronary sinus fistulas with giant left circumflex artery aneurysm and multivalvular infective endocarditis. The operation was conducted using conventional ascending aorta and bicaval bypass under moderate hypothermia. The retrograde infusion of histidine-tryptophan-ketoglutarate cardioplegic solution (Custodiol®) was utilized for myocardial protection. Vegetations were observed on aortic and mitral valve leaflets. Double valve replacement (St. Jude Medical Regent [23 and 29 mm in aortic and mitral positions]; St. Jude Medical Inc, St Paul, MN) was performed. After completing the valve replacements, the CS and tricuspid valve were examined through a right atriotomy. Four fistulas were visually confirmed inside the CS. Each fistula was approximately 1.5 mm in diameter. No vegetation on the tricuspid valve was observed, but significant central regurgitation was present. After direct suturing was implemented with pledgetted 4 − 0 Prolene to close the CS fistulas, de-airing maneuvers followed and the cross clamp was released. At that point we assessed whether any remaining shunt flow through the fistula was present. At this time, a strong shunt flow was observed inside CS (Fig.  2 ), because it was difficult to secure a surgical view due to the strong shunt flow just inside the coronary sinus, we first tried to secure a view by inserting a pump sucker into the coronary sinus to drain the blood. Nevertheless, because the visibility was poor, we were able to secure the view by blocking the entrance of the strong shunt flow with forcep. And additional direct suturing was performed, and additional direct suturing was performed. Moreover, tricuspid annuloplasty (TAP) was performed using 32 mm Edwards MC 3 ring (Edwards LifeSciences, Irvine, CA), and the surgery was completed. The postoperative course was uneventful, and there were no complications. On the follow-up, the transthoracic echocardiogram and chest computed tomography did not demonstrate any abnormal findings (Fig. 3 ). The preoperative blood culture grew Propionibacterium propionicum . Empirical antibiotic treatment was initiated with ceftriaxone, doxycycline, and vancomycin. However, intraoperative tissue culture showed no growth. After a discussion with the Department of Infectious Diseases, doxycycline was discontinued, and intravenous antibiotics (ceftriaxone; 2 g one a day, vancomycin; 1 g one a day) were administered for 8 weeks. To assess the remnant shunt of CS fistula, first-pass radionuclide angiocardiography using technetium 99 m diethylamine triamine pentaacetic acid (TC99m-DTPA) was performed. The Qp/Qs ratio was measured at 1.2, indicating no residual shunt flow due to fistulas. The patient was discharged after switching to oral antibiotics (amoxicillin 1 g tid) and ≥ 2 weeks of medication. He did not complain of any symptoms or showed abnormal murmurs during the follow-up. No prosthetic valve dysfunction or recurrent abnormal flow were recorded were recorded at TTE over 18 months of follow up.

Cardiac computed tomography indicated that (A) LCx (white solid arrow) was enlarged to an overall diameter of approximately 1.2 cm while (B) multiple left circumflex CAFs (white blank arrow) draining into CS were identified

Intraoperative images; (A) direct suturing was performed using 4 − 0 prolene with pledget to close CS fistulas; (B) after de-airing and releasing aortic cross-clamp, it was checked whether any remaining shunt flow through fistula was observed; at this time, a strong shunt flow (white dotted arrow) was observed inside CS (white oval solid line)

Postoperative images; (A) postoperative chest x-ray, (B) postoperative cardiac computed tomography indicated no residual (white blank arrow) fistula between LCx and CS

CAF is a rare disease, occurring in 0.002% general population and representing 0.4% cardiac malformations [ 1 ]. The origin of CAF is found in the right coronary artery, left anterior descending coronary artery, and LCx in 50–60%, 25–42%, and 18.8% of cases. The termination of the fistula is drained in this order: pulmonary artery, right ventricle, right atrium, and CS. Single fistulas are the most commonly observed, ranging from 74 to 90%, whereas multiple fistulas occur in 10.7–16% of all cases of CAFs [ 1 , 2 ]. Thus, the present case (multiple LCx to CS fistulas) is a rare case among CAFs, considering the origin, termination, and number of fistulas.

Most CAFs are asymptomatic; however, when symptoms occur, the most commonly observed symptoms are exertional dyspnea, fatigue and angina. In addition, CAFs tend to grow larger with age and may be accompanied by various complications in older age. These complications primarily include the following:

Volume overload of the cardiac chamber can cause congestive heart failure, left ventricle hypertrophy, and arrhythmia.

Coronary dilation and aneurysmal changes due to shunt flow, and myocardial ischemia, may occur. When the diameter is four times larger than normal, or > 8 mm, it is classified as a giant aneurysm.

It may be accompanied by valvular dysfunction and infective endocarditis [ 1 , 2 ].

In this case, the 39-year-old patient showed no previous major symptoms but giant aneurysmal changes in the LCx which was enlarged by > 8 mm and associated with infective endocarditis. Therefore, even if small CAFs and asymptomatic cases are detected, long-term follow-up is deemed necessary.

Diagnostic evaluation was performed by detecting anatomical abnormalities via TTE, transesophageal echocardiography, and computed tomography angiography. Moreover, to quantitatively evaluate the amount of left-to-right shunt, Qp/Qs ratio can be measured via first-pass radionuclide angiocardiography with 93% sensitivity and 97% specificity [ 3 ]. Although this test was not performed preoperatively due to emergency surgery, no significant remaining shunts were observed post-surgery.

CAF can be categorized into two types based on the connection method between origin and drain. “Side-to-side fistula” is proximal CAF. In this type, fistula connects to the coronary artery in the middle, resulting in dilation of the coronary artery at the proximal site of fistula opening. On the contrary, “End-to-side fistula” is distal CAF. Unlike proximal CAF, it is characterized by diffuse dilation, as the coronary artery’s endpoint forms the fistula while connecting to the drain site. The present case was diagnosed as an end-to-side fistula, which has diffuse dilatation.

Based on the 2009 ACC/AHA guidelines, for fistulas accompanied by symptoms, percutaneous or surgical closure should be indicated, which is Class I recommendation with Level of Evidence C [ 4 ]. Even if the indications for interventional treatment are not met, ongoing close monitoring is necessary due to the possibility of dilation and tortuous changes developing over time.

The surgical approach to treat fistulas depends on the anatomical conditions and type of fistula. If the fistula is exposed on epicardium, it can be divided and ligated or oversewn by making an arteriotomy. In cases where accessing fistula externally is challenging, an intracardiac approach can be applied [ 1 ]. The present case was diagnosed as “end-to-side” type, and an intracardiac approach was performed. After opening RA and confirming multiple fistulas in CS, direct suturing was attempted. If fistulas near CS are relatively confirmed, direct suturing is sufficiently possible. Moreover, it is possible to visually check whether any shunts remain immediately after releasing ACC, allowing additional suture to be taken. In this case, the surgery was able to be completed with additional sutures due to the presence of a strong remaining shunt after ACC was released. In this case, we report a rare case of multiple coronary artery to CS fistulas with giant left circumflex artery and multivalvular infective endocarditis.

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Data were obtained from health medical examination data from Ulsan University Hospital. Data sharing is not applicable.

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Acknowledgements

The authors would like to thank Enago ( www.enago.co.kr ) for the English language review.

The authors declare that they have received no external funding for this study.

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Sang Bin Shin

Department of Thoracic and Cardiovascular Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, 877, Bangeojinsunhwando-ro, Dong-gu, Ulsan, 44033, Republic of Korea

Won Kyoun Park, Jae Won Choi, Jong Pil Jung, Chang Ryul Park, Yong Jik Lee & Gwan Sic Kim

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Shin and Kim wrote the main manuscripts. Shin, Park, and Choi prepared Figs. 1 and 2. All authors reviewed the manuscript.

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Shin, S.B., Park, W.K., Choi, J.W. et al. Surgical management of multiple coronary artery to coronary sinus fistulas with giant left circumflex artery and multivalvular infective endocarditis. J Cardiothorac Surg 19 , 186 (2024). https://doi.org/10.1186/s13019-024-02657-3

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DOI : https://doi.org/10.1186/s13019-024-02657-3

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Exploring the Relationship between Urban Vibrancy and Built Environment Using Multi-Source Data: Case Study in Munich

• Sun, Maopeng
• Zhao, Xiyang

Urbanization has profoundly reshaped the patterns and forms of modern urban landscapes. Understanding how urban transportation and mobility are affected by spatial planning is vital. Urban vibrancy, as a crucial metric for monitoring urban development, contributes to data-driven planning and sustainable growth. However, empirical studies on the relationship between urban vibrancy and the built environment in European cities remain limited, lacking consensus on the contribution of the built environment. This study employs Munich as a case study, utilizing night-time light, housing prices, social media, points of interest (POIs), and NDVI data to measure various aspects of urban vibrancy while constructing a comprehensive assessment framework. Firstly, the spatial distribution patterns and spatial correlation of various types of urban vibrancy are revealed. Concurrently, based on the 5Ds built environment indicator system, the multi-dimensional influence on urban vibrancy is investigated. Subsequently, the Geodetector model explores the heterogeneity between built environment indicators and comprehensive vibrancy along with its economic, social, cultural, and environmental dimensions, elucidating their influence mechanism. The results show the following: (1) The comprehensive vibrancy in Munich exhibits a pronounced uneven distribution, with a higher vibrancy in central and western areas and lower vibrancy in northern and western areas. High-vibrancy areas are concentrated along major roads and metro lines located in commercial and educational centers. (2) Among multiple models, the geographically weighted regression (GWR) model demonstrates the highest explanatory efficacy on the relationship between the built environment and vibrancy. (3) Economic, social, and comprehensive vibrancy are significantly influenced by the built environment, with substantial positive effects from the POI density, building density, and road intersection density, while mixed land use shows little impact. (4) Interactions among built environment factors significantly impact comprehensive vibrancy, with synergistic interactions among the population density, building density, and POI density generating positive effects. These findings provide valuable insights for optimizing the resource allocation and functional layout in Munich, emphasizing the complex spatiotemporal relationship between the built environment and urban vibrancy while offering crucial guidance for planning.

• urban vibrancy;
• built environment;
• spatiotemporal effect;
• multi-source data;
• Geodetector;
• GIS Analysis;

Multiple case study design: the example of place marketing research

• Original Article
• Published: 05 February 2020
• Volume 17 , pages 50–62, ( 2021 )

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• Marek Ćwiklicki   ORCID: orcid.org/0000-0002-5298-0210 1 &
• Kamila Pilch 1  

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The objective of this paper is to discuss the specificity of multiple case study (MCS) research design using analysis of research description realized according to this strategy in the field of place branding and place marketing published between 1976 and 2016 in scholarly journals. Selecting cases and cases’ context are most frequently explained in place marketing articles where findings are results of MCS research. The choice of a case study as a research strategy and limitations of the studies are less frequently justified in investigated papers. Our analysis shows that the authors should pay more attention to elements characteristic for methodological rigour in their descriptions of the research method. For this purpose, we prepared a checklist. We have discussed in detail key methodological issues for MCS. Moreover, we have formulated guidelines for improving research methodology’s descriptions in scholarly papers. It should lead to an increase in methodological rigour in future research reports. Therefore, researchers will find out suggestions for studying phenomena within place branding domain.

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Acknowledgements

We would like to thank dr Renaud Vuignier for sharing his journal database and the reviewers of this journal for their insightful and constructive comments towards improving our manuscript.

Funding was provided by Cracow University of Economics.

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Ćwiklicki, M., Pilch, K. Multiple case study design: the example of place marketing research. Place Brand Public Dipl 17 , 50–62 (2021). https://doi.org/10.1057/s41254-020-00159-2

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Revised : 07 September 2019

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DOI : https://doi.org/10.1057/s41254-020-00159-2

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