SAN DIEGO – Oral, once-daily treatment with canagliflozin significantly reduced the risk of cardiovascular events, compared with placebo, among more than 10,000 patients with type 2 diabetes at high risk of cardiovascular disease.

After an average of 188 weeks of follow-up, the combined rate of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke was 26.9 events per 1,000 person-years of canagliflozin treatment and 31.5 events per 1,000 person-years of placebo treatment (hazard ratio, 0.86; 95% confidence interval, 0.75-0.97; P less than .001 for noninferiority; P = .02 for superiority) in the Canagliflozin Cardiovascular Assessment Study (CANVAS) and its sister trial, CANVAS-R, investigators reported at the annual scientific sessions of the American Diabetes Association. The report was published simultaneously in the New England Journal of Medicine (N Engl J Med. 2017 Jun 12. doi: 10.1056/NEJMoa1611925).

SAN DIEGO – Oral, once-daily treatment with canagliflozin significantly reduced the risk of cardiovascular events, compared with placebo, among more than 10,000 patients with type 2 diabetes at high risk of cardiovascular disease.

After an average of 188 weeks of follow-up, the combined rate of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke was 26.9 events per 1,000 person-years of canagliflozin treatment and 31.5 events per 1,000 person-years of placebo treatment (hazard ratio, 0.86; 95% confidence interval, 0.75-0.97; P less than .001 for noninferiority; P = .02 for superiority) in the Canagliflozin Cardiovascular Assessment Study (CANVAS) and its sister trial, CANVAS-R, investigators reported at the annual scientific sessions of the American Diabetes Association. The report was published simultaneously in the New England Journal of Medicine (N Engl J Med. 2017 Jun 12. doi: 10.1056/NEJMoa1611925).

SAN DIEGO – Oral, once-daily treatment with canagliflozin significantly reduced the risk of cardiovascular events, compared with placebo, among more than 10,000 patients with type 2 diabetes at high risk of cardiovascular disease.

After an average of 188 weeks of follow-up, the combined rate of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke was 26.9 events per 1,000 person-years of canagliflozin treatment and 31.5 events per 1,000 person-years of placebo treatment (hazard ratio, 0.86; 95% confidence interval, 0.75-0.97; P less than .001 for noninferiority; P = .02 for superiority) in the Canagliflozin Cardiovascular Assessment Study (CANVAS) and its sister trial, CANVAS-R, investigators reported at the annual scientific sessions of the American Diabetes Association. The report was published simultaneously in the New England Journal of Medicine (N Engl J Med. 2017 Jun 12. doi: 10.1056/NEJMoa1611925).

The Diagnosis: Nevus Lipomatosus Cutaneous Superficialis

A punch biopsy was obtained from a skin lesion, which showed orthokeratosis, irregular acanthosis, papillomatosis, intense edema in the upper dermis, and mature fat lobules that dissected collagen fibers in the reticular dermis (Figure). Classical-type nevus lipomatosus cutaneous superficialis (NLCS) was diagnosed based on these clinical and histopathological findings. The patient was referred to the plastic surgery clinic for total excision of all lesions.

Nevus lipomatosus cutaneous superficialis is a rare hamartoma characterized by ectopic deposition of mature adipose tissue in the dermis.¹ It was first described by Hoffmann and Zurhelle² in 1921. Clinically, NLCS is classified into 2 subtypes: classical (multiple) and solitary. Classical-type NLCS is characterized by multiple pedunculated or sessile, soft, cerebriform, yellowish papules and nodules, especially in the pelvic area. Solitary-type NLCS presents as a sessile papule or nodule with no predilection for localization. Although the classical form of NLCS generally occurs in the first 2 decades of life, the solitary form usually appears in adulthood.³ Nevus lipomatosus cutaneous superficialis has no gender predilection and there is no genetic or congenital defect association.^1,4

The pathogenesis of NLCS still is unknown, but some theories have been proposed, such as the development of adipose metaplasia secondary to degeneration of connective tissue, the formation of a true nevus resulting from heterotopic development of adipose tissue, and the development of mature adipocytes from pericytes in dermal vessels.^1,5 

Histopathology of NLCS shows clusters of ectopic mature adipose tissue in varying rates (10%-50%) between collagen bundles in the dermis. Characteristically, there is no connection between the ectopic mature adipose tissue and the subcutaneous adipose tissue.³ The differential diagnosis of NLCS includes neurofibroma, lymphangioma, sebaceous nevus, fibroepithelial polyps, leiomyoma, and lipomas.^1,6

Treatment of NLCS generally involves basic surgical excision; however, patients treated with CO₂ laser also have been reported in the literature.⁵ Because of the growth tendency and the large size of the classical form of NLCS, recurrence may occur, as in our case. In such cases, gradual surgical excision is recommended.⁵ We present this case to indicate that undesirable surgical results or relapse may occur in untreated patients because of lesion growth and delayed diagnosis.

The Diagnosis: Nevus Lipomatosus Cutaneous Superficialis

A punch biopsy was obtained from a skin lesion, which showed orthokeratosis, irregular acanthosis, papillomatosis, intense edema in the upper dermis, and mature fat lobules that dissected collagen fibers in the reticular dermis (Figure). Classical-type nevus lipomatosus cutaneous superficialis (NLCS) was diagnosed based on these clinical and histopathological findings. The patient was referred to the plastic surgery clinic for total excision of all lesions.

Nevus lipomatosus cutaneous superficialis is a rare hamartoma characterized by ectopic deposition of mature adipose tissue in the dermis.¹ It was first described by Hoffmann and Zurhelle² in 1921. Clinically, NLCS is classified into 2 subtypes: classical (multiple) and solitary. Classical-type NLCS is characterized by multiple pedunculated or sessile, soft, cerebriform, yellowish papules and nodules, especially in the pelvic area. Solitary-type NLCS presents as a sessile papule or nodule with no predilection for localization. Although the classical form of NLCS generally occurs in the first 2 decades of life, the solitary form usually appears in adulthood.³ Nevus lipomatosus cutaneous superficialis has no gender predilection and there is no genetic or congenital defect association.^1,4

The pathogenesis of NLCS still is unknown, but some theories have been proposed, such as the development of adipose metaplasia secondary to degeneration of connective tissue, the formation of a true nevus resulting from heterotopic development of adipose tissue, and the development of mature adipocytes from pericytes in dermal vessels.^1,5 

Histopathology of NLCS shows clusters of ectopic mature adipose tissue in varying rates (10%-50%) between collagen bundles in the dermis. Characteristically, there is no connection between the ectopic mature adipose tissue and the subcutaneous adipose tissue.³ The differential diagnosis of NLCS includes neurofibroma, lymphangioma, sebaceous nevus, fibroepithelial polyps, leiomyoma, and lipomas.^1,6

Treatment of NLCS generally involves basic surgical excision; however, patients treated with CO₂ laser also have been reported in the literature.⁵ Because of the growth tendency and the large size of the classical form of NLCS, recurrence may occur, as in our case. In such cases, gradual surgical excision is recommended.⁵ We present this case to indicate that undesirable surgical results or relapse may occur in untreated patients because of lesion growth and delayed diagnosis.

The Diagnosis: Nevus Lipomatosus Cutaneous Superficialis

A punch biopsy was obtained from a skin lesion, which showed orthokeratosis, irregular acanthosis, papillomatosis, intense edema in the upper dermis, and mature fat lobules that dissected collagen fibers in the reticular dermis (Figure). Classical-type nevus lipomatosus cutaneous superficialis (NLCS) was diagnosed based on these clinical and histopathological findings. The patient was referred to the plastic surgery clinic for total excision of all lesions.

Nevus lipomatosus cutaneous superficialis is a rare hamartoma characterized by ectopic deposition of mature adipose tissue in the dermis.¹ It was first described by Hoffmann and Zurhelle² in 1921. Clinically, NLCS is classified into 2 subtypes: classical (multiple) and solitary. Classical-type NLCS is characterized by multiple pedunculated or sessile, soft, cerebriform, yellowish papules and nodules, especially in the pelvic area. Solitary-type NLCS presents as a sessile papule or nodule with no predilection for localization. Although the classical form of NLCS generally occurs in the first 2 decades of life, the solitary form usually appears in adulthood.³ Nevus lipomatosus cutaneous superficialis has no gender predilection and there is no genetic or congenital defect association.^1,4

The pathogenesis of NLCS still is unknown, but some theories have been proposed, such as the development of adipose metaplasia secondary to degeneration of connective tissue, the formation of a true nevus resulting from heterotopic development of adipose tissue, and the development of mature adipocytes from pericytes in dermal vessels.^1,5 

Histopathology of NLCS shows clusters of ectopic mature adipose tissue in varying rates (10%-50%) between collagen bundles in the dermis. Characteristically, there is no connection between the ectopic mature adipose tissue and the subcutaneous adipose tissue.³ The differential diagnosis of NLCS includes neurofibroma, lymphangioma, sebaceous nevus, fibroepithelial polyps, leiomyoma, and lipomas.^1,6

Treatment of NLCS generally involves basic surgical excision; however, patients treated with CO₂ laser also have been reported in the literature.⁵ Because of the growth tendency and the large size of the classical form of NLCS, recurrence may occur, as in our case. In such cases, gradual surgical excision is recommended.⁵ We present this case to indicate that undesirable surgical results or relapse may occur in untreated patients because of lesion growth and delayed diagnosis.

An investigational quadrivalent flu vaccine formulated to be less pyrogenic had noninferior immunogenicity, compared with a U.S.-licensed vaccine, in children aged 5-17 years, Jolanta Airey, MD, of Seqirus in Parkville, Australia, and her associates reported.

In 2010, in Australia and New Zealand, use of a trivalent flu vaccine was associated with unexpected reports of fever and febrile seizures in children aged younger than 9 years. Research into the issue suggested that “degraded RNA fragments delivered by residual lipids activated the release of proinflammatory cytokines, which stimulated the pyrogenic response in children,” the study authors noted. “Increasing the level of sodium taurodeoxycholate (TDOC) to split the B strain in particular resulted in decreased levels of residual lipids and attenuated proinflammatory cytokine signals.”

copyright luiscar/Thinkstock

[email protected]

An investigational quadrivalent flu vaccine formulated to be less pyrogenic had noninferior immunogenicity, compared with a U.S.-licensed vaccine, in children aged 5-17 years, Jolanta Airey, MD, of Seqirus in Parkville, Australia, and her associates reported.

In 2010, in Australia and New Zealand, use of a trivalent flu vaccine was associated with unexpected reports of fever and febrile seizures in children aged younger than 9 years. Research into the issue suggested that “degraded RNA fragments delivered by residual lipids activated the release of proinflammatory cytokines, which stimulated the pyrogenic response in children,” the study authors noted. “Increasing the level of sodium taurodeoxycholate (TDOC) to split the B strain in particular resulted in decreased levels of residual lipids and attenuated proinflammatory cytokine signals.”

copyright luiscar/Thinkstock

[email protected]

An investigational quadrivalent flu vaccine formulated to be less pyrogenic had noninferior immunogenicity, compared with a U.S.-licensed vaccine, in children aged 5-17 years, Jolanta Airey, MD, of Seqirus in Parkville, Australia, and her associates reported.

In 2010, in Australia and New Zealand, use of a trivalent flu vaccine was associated with unexpected reports of fever and febrile seizures in children aged younger than 9 years. Research into the issue suggested that “degraded RNA fragments delivered by residual lipids activated the release of proinflammatory cytokines, which stimulated the pyrogenic response in children,” the study authors noted. “Increasing the level of sodium taurodeoxycholate (TDOC) to split the B strain in particular resulted in decreased levels of residual lipids and attenuated proinflammatory cytokine signals.”

copyright luiscar/Thinkstock

[email protected]

As lifelong learners, physicians are encouraged and expected to share their knowledge base with budding residents and students. Effective communication is essential to the utmost delivery of clinical knowledge and pearls. Lecture delivery is important for all stages of learning, and adapting efficient techniques early in one's career is critical for the transmission of ideas and teaching points. These tips were created to help formulate guidelines for physician presentations and are open for interpretation. These well-meaning suggestions can be integrated into one's toolbox to foster an enthusiastic educational arena.

Step 1: Know Your Key Message 

First and foremost, one should ruminate over the overall message of the lecture. Consider at least 3 main points you want the learner to gain and remember on completion of the lecture. Additionally, it is crucial to think about the audience who will be present for your message and how to deliver your ideas clearly and effectively. Be cognizant of the knowledge base of your listeners and gauge how much initial background information is needed; conversely, if the audience is familiar with the material, excessive introductory material may be unnecessary and cause inattentiveness. Simplicity, both within the inherent message itself and the content and layout, can ameliorate the transmission of data regardless of the audience. A mentor once told me that no slide should contain more than 13 lines of text. Furthermore, if you are counting the number of lines, then you likely need to reduce the text and simplify the slide. Each slide should contain a maximum of 3 or 4 bullet points.¹ Convoluted figures should be avoided and key points should be highlighted. Overall, know your take-home message and provide the listener with simplistic text and images to convey the key ideas at their educational level.

Step 2: Prepare

Preparation is of utmost importance. Reading over the slides several times prior to the presentation is vital. You are the assumed expert on the topic and meticulously knowing the subject matter helps with the confidence of your delivery. Ease of subject matter also helps you, as the presenter, to rely less on verbatim reading of the slides and allows you to interact more with your audience. It is important to be familiar with the order of your presentation as well as the phrases and figures provided.² Flipping back and forth through slides can be distracting to the audience and can make the order of your presentation seem incongruous, presenting as a hastily constructed lecture. If you are prepared, you can engage your audience and provide additional information that is not on the slides to maintain interest. Remember that reading the slides can reduce your voice to a monotone, subtracting enthusiasm and energy from the delivery of your talk.² Rehearsal helps give you the freedom to confidently and proudly present your subject material.

Step 3: Be Animated 

You are the main attraction and the performer of this lecture. Radiate the confidence you gained from being prepared with the ability to engage in eye contact and gestures as needed to convey your point. Regularly shift your focus around the room to attempt to involve as many people as possible in your talk.² Your main focus should be your audience and not your slides; the slides should simply help guide your talk.³ During your presentation, you also can ask rhetorical questions that you can then answer to keep the group engaged (eg, "So, what does this tell us?" or "What would you do next?"). These questions demonstrate to your audience that you are interested in their attention and can help reciprocate the enthusiasm. Use language that involves your audience as a group participant. For example, when looking at visual aids, introduce them by saying "If we look at this table, we can see that . . ." or "This figure shows us that . . ."^2,3 Additionally, be cognizant of the volume and pace of your voice. During key points, you may want to slightly raise your voice and slow your pace for emphasis. Anxiety can make all presenters speed through their material; however, try to be mindful of the rhythm of your speech. With preparation you should be able to accurately gauge the length of your presentation but also adapt to the necessary time constraints if too much time is spent on one point early on. Most would believe that all good lectures end at least a few minutes early to allow for questions and comprehension of the material as well as to provide your audience with time to move on to their next engagement or clinical duty. 

Step 4: Encourage Active Participation

Active audience participation is shown by a multitude of studies to provide the highest level of comprehension.^4,5 In a crossover study conducted by Bleske et al,⁴ 30 students were divided into 2 groups and were taught 6 therapeutic topics, with 3 topics provided by conventional lecture and 3 topics taught by team-based learning. At the end of the educational series, the students were surveyed to evaluate their confidence and attitudes. Students demonstrated not only higher examination scores with team-based learning but higher confidence in their ability to transmit the information garnered through therapeutic recommendations.⁴ Although small, this study highlights the intuitive notion that active learning with subject material, either by sharing ideas with colleagues or having small brainstorming discussions throughout lectures, helps consolidate the information for long-term memory and comprehension.

Additionally, teaching in a medical environment can present unique challenges, as participants may feel anxiety over having right or wrong answers due to fear of inadequacy among their scholarly peers. Neher et al⁶ proposed a 5-step "microskills" model for teaching young physicians, and although it is intended for a clinical setting, it also can be applied to engaging and answering questions from a medical audience in general. Their model focuses on the teacher, or in our case the lecturer, asking a question and then applying the following model: (1) get a commitment, (2) probe for supporting evidence, (3) teach general rules, (4) reinforce what was done right, and (5) correct mistakes.⁶ After asking your question, the student commits to an answer and must then provide supporting details for their choice, thus feeling more responsible for their collaborative role in problem-solving. Based on their answer, you can then teach your general rule, provide positive feedback on what the student said accurately, and ultimately correct any erroneous information. This prototype of learning is best utilized in the clinical setting but also can enhance participant engagement in lectures while maintaining an inviting educational environment. 

Step 5: Summarize 

Lastly, conclude your presentation with at least 3 memorable points. What was the point of the presentation? What message do you want your audience to take with them and apply to clinical care? Reiterating the key points through repetition is crucial for long-term memory. Leave the audience with additional thoughts for exploration and subsequent discussion. How can your work or topic be further translated into additional projects for investigation? If the lecture material contains abundant clinical information beyond 3 points, a handout can be helpful to avoid having learners struggling to keep up with notes. This piece of take-home material can serve as a tool for subsequent study and to stimulate enhanced memory of the subject material provided. A strong concluding message can consolidate and remind learners of the scope of the topic and highlight the vital information that should be retained.

Final Thoughts

In summary, the clinical lecturer provides a unique teaching experience, and all physicians should feel proficient in formulating and delivering an educational lecture. These simple tips that call for the teacher to know and prepare his/her key message to deliver an animated and engaged presentation and then to summarize key findings are suggestions for the utmost transmission of data and ideas for all learners.

Acknowledgment
A special thank you to Joan E. St. Onge, MD (Miami, Florida), for her help providing resources for this topic. 

As lifelong learners, physicians are encouraged and expected to share their knowledge base with budding residents and students. Effective communication is essential to the utmost delivery of clinical knowledge and pearls. Lecture delivery is important for all stages of learning, and adapting efficient techniques early in one's career is critical for the transmission of ideas and teaching points. These tips were created to help formulate guidelines for physician presentations and are open for interpretation. These well-meaning suggestions can be integrated into one's toolbox to foster an enthusiastic educational arena.

Step 1: Know Your Key Message 

First and foremost, one should ruminate over the overall message of the lecture. Consider at least 3 main points you want the learner to gain and remember on completion of the lecture. Additionally, it is crucial to think about the audience who will be present for your message and how to deliver your ideas clearly and effectively. Be cognizant of the knowledge base of your listeners and gauge how much initial background information is needed; conversely, if the audience is familiar with the material, excessive introductory material may be unnecessary and cause inattentiveness. Simplicity, both within the inherent message itself and the content and layout, can ameliorate the transmission of data regardless of the audience. A mentor once told me that no slide should contain more than 13 lines of text. Furthermore, if you are counting the number of lines, then you likely need to reduce the text and simplify the slide. Each slide should contain a maximum of 3 or 4 bullet points.¹ Convoluted figures should be avoided and key points should be highlighted. Overall, know your take-home message and provide the listener with simplistic text and images to convey the key ideas at their educational level.

Step 2: Prepare

Preparation is of utmost importance. Reading over the slides several times prior to the presentation is vital. You are the assumed expert on the topic and meticulously knowing the subject matter helps with the confidence of your delivery. Ease of subject matter also helps you, as the presenter, to rely less on verbatim reading of the slides and allows you to interact more with your audience. It is important to be familiar with the order of your presentation as well as the phrases and figures provided.² Flipping back and forth through slides can be distracting to the audience and can make the order of your presentation seem incongruous, presenting as a hastily constructed lecture. If you are prepared, you can engage your audience and provide additional information that is not on the slides to maintain interest. Remember that reading the slides can reduce your voice to a monotone, subtracting enthusiasm and energy from the delivery of your talk.² Rehearsal helps give you the freedom to confidently and proudly present your subject material.

Step 3: Be Animated 

You are the main attraction and the performer of this lecture. Radiate the confidence you gained from being prepared with the ability to engage in eye contact and gestures as needed to convey your point. Regularly shift your focus around the room to attempt to involve as many people as possible in your talk.² Your main focus should be your audience and not your slides; the slides should simply help guide your talk.³ During your presentation, you also can ask rhetorical questions that you can then answer to keep the group engaged (eg, "So, what does this tell us?" or "What would you do next?"). These questions demonstrate to your audience that you are interested in their attention and can help reciprocate the enthusiasm. Use language that involves your audience as a group participant. For example, when looking at visual aids, introduce them by saying "If we look at this table, we can see that . . ." or "This figure shows us that . . ."^2,3 Additionally, be cognizant of the volume and pace of your voice. During key points, you may want to slightly raise your voice and slow your pace for emphasis. Anxiety can make all presenters speed through their material; however, try to be mindful of the rhythm of your speech. With preparation you should be able to accurately gauge the length of your presentation but also adapt to the necessary time constraints if too much time is spent on one point early on. Most would believe that all good lectures end at least a few minutes early to allow for questions and comprehension of the material as well as to provide your audience with time to move on to their next engagement or clinical duty. 

Step 4: Encourage Active Participation

Active audience participation is shown by a multitude of studies to provide the highest level of comprehension.^4,5 In a crossover study conducted by Bleske et al,⁴ 30 students were divided into 2 groups and were taught 6 therapeutic topics, with 3 topics provided by conventional lecture and 3 topics taught by team-based learning. At the end of the educational series, the students were surveyed to evaluate their confidence and attitudes. Students demonstrated not only higher examination scores with team-based learning but higher confidence in their ability to transmit the information garnered through therapeutic recommendations.⁴ Although small, this study highlights the intuitive notion that active learning with subject material, either by sharing ideas with colleagues or having small brainstorming discussions throughout lectures, helps consolidate the information for long-term memory and comprehension.

Additionally, teaching in a medical environment can present unique challenges, as participants may feel anxiety over having right or wrong answers due to fear of inadequacy among their scholarly peers. Neher et al⁶ proposed a 5-step "microskills" model for teaching young physicians, and although it is intended for a clinical setting, it also can be applied to engaging and answering questions from a medical audience in general. Their model focuses on the teacher, or in our case the lecturer, asking a question and then applying the following model: (1) get a commitment, (2) probe for supporting evidence, (3) teach general rules, (4) reinforce what was done right, and (5) correct mistakes.⁶ After asking your question, the student commits to an answer and must then provide supporting details for their choice, thus feeling more responsible for their collaborative role in problem-solving. Based on their answer, you can then teach your general rule, provide positive feedback on what the student said accurately, and ultimately correct any erroneous information. This prototype of learning is best utilized in the clinical setting but also can enhance participant engagement in lectures while maintaining an inviting educational environment. 

Step 5: Summarize 

Lastly, conclude your presentation with at least 3 memorable points. What was the point of the presentation? What message do you want your audience to take with them and apply to clinical care? Reiterating the key points through repetition is crucial for long-term memory. Leave the audience with additional thoughts for exploration and subsequent discussion. How can your work or topic be further translated into additional projects for investigation? If the lecture material contains abundant clinical information beyond 3 points, a handout can be helpful to avoid having learners struggling to keep up with notes. This piece of take-home material can serve as a tool for subsequent study and to stimulate enhanced memory of the subject material provided. A strong concluding message can consolidate and remind learners of the scope of the topic and highlight the vital information that should be retained.

Final Thoughts

In summary, the clinical lecturer provides a unique teaching experience, and all physicians should feel proficient in formulating and delivering an educational lecture. These simple tips that call for the teacher to know and prepare his/her key message to deliver an animated and engaged presentation and then to summarize key findings are suggestions for the utmost transmission of data and ideas for all learners.

Acknowledgment
A special thank you to Joan E. St. Onge, MD (Miami, Florida), for her help providing resources for this topic. 

As lifelong learners, physicians are encouraged and expected to share their knowledge base with budding residents and students. Effective communication is essential to the utmost delivery of clinical knowledge and pearls. Lecture delivery is important for all stages of learning, and adapting efficient techniques early in one's career is critical for the transmission of ideas and teaching points. These tips were created to help formulate guidelines for physician presentations and are open for interpretation. These well-meaning suggestions can be integrated into one's toolbox to foster an enthusiastic educational arena.

Step 1: Know Your Key Message 

First and foremost, one should ruminate over the overall message of the lecture. Consider at least 3 main points you want the learner to gain and remember on completion of the lecture. Additionally, it is crucial to think about the audience who will be present for your message and how to deliver your ideas clearly and effectively. Be cognizant of the knowledge base of your listeners and gauge how much initial background information is needed; conversely, if the audience is familiar with the material, excessive introductory material may be unnecessary and cause inattentiveness. Simplicity, both within the inherent message itself and the content and layout, can ameliorate the transmission of data regardless of the audience. A mentor once told me that no slide should contain more than 13 lines of text. Furthermore, if you are counting the number of lines, then you likely need to reduce the text and simplify the slide. Each slide should contain a maximum of 3 or 4 bullet points.¹ Convoluted figures should be avoided and key points should be highlighted. Overall, know your take-home message and provide the listener with simplistic text and images to convey the key ideas at their educational level.

Step 2: Prepare

Preparation is of utmost importance. Reading over the slides several times prior to the presentation is vital. You are the assumed expert on the topic and meticulously knowing the subject matter helps with the confidence of your delivery. Ease of subject matter also helps you, as the presenter, to rely less on verbatim reading of the slides and allows you to interact more with your audience. It is important to be familiar with the order of your presentation as well as the phrases and figures provided.² Flipping back and forth through slides can be distracting to the audience and can make the order of your presentation seem incongruous, presenting as a hastily constructed lecture. If you are prepared, you can engage your audience and provide additional information that is not on the slides to maintain interest. Remember that reading the slides can reduce your voice to a monotone, subtracting enthusiasm and energy from the delivery of your talk.² Rehearsal helps give you the freedom to confidently and proudly present your subject material.

Step 3: Be Animated 

You are the main attraction and the performer of this lecture. Radiate the confidence you gained from being prepared with the ability to engage in eye contact and gestures as needed to convey your point. Regularly shift your focus around the room to attempt to involve as many people as possible in your talk.² Your main focus should be your audience and not your slides; the slides should simply help guide your talk.³ During your presentation, you also can ask rhetorical questions that you can then answer to keep the group engaged (eg, "So, what does this tell us?" or "What would you do next?"). These questions demonstrate to your audience that you are interested in their attention and can help reciprocate the enthusiasm. Use language that involves your audience as a group participant. For example, when looking at visual aids, introduce them by saying "If we look at this table, we can see that . . ." or "This figure shows us that . . ."^2,3 Additionally, be cognizant of the volume and pace of your voice. During key points, you may want to slightly raise your voice and slow your pace for emphasis. Anxiety can make all presenters speed through their material; however, try to be mindful of the rhythm of your speech. With preparation you should be able to accurately gauge the length of your presentation but also adapt to the necessary time constraints if too much time is spent on one point early on. Most would believe that all good lectures end at least a few minutes early to allow for questions and comprehension of the material as well as to provide your audience with time to move on to their next engagement or clinical duty. 

Step 4: Encourage Active Participation

Active audience participation is shown by a multitude of studies to provide the highest level of comprehension.^4,5 In a crossover study conducted by Bleske et al,⁴ 30 students were divided into 2 groups and were taught 6 therapeutic topics, with 3 topics provided by conventional lecture and 3 topics taught by team-based learning. At the end of the educational series, the students were surveyed to evaluate their confidence and attitudes. Students demonstrated not only higher examination scores with team-based learning but higher confidence in their ability to transmit the information garnered through therapeutic recommendations.⁴ Although small, this study highlights the intuitive notion that active learning with subject material, either by sharing ideas with colleagues or having small brainstorming discussions throughout lectures, helps consolidate the information for long-term memory and comprehension.

Additionally, teaching in a medical environment can present unique challenges, as participants may feel anxiety over having right or wrong answers due to fear of inadequacy among their scholarly peers. Neher et al⁶ proposed a 5-step "microskills" model for teaching young physicians, and although it is intended for a clinical setting, it also can be applied to engaging and answering questions from a medical audience in general. Their model focuses on the teacher, or in our case the lecturer, asking a question and then applying the following model: (1) get a commitment, (2) probe for supporting evidence, (3) teach general rules, (4) reinforce what was done right, and (5) correct mistakes.⁶ After asking your question, the student commits to an answer and must then provide supporting details for their choice, thus feeling more responsible for their collaborative role in problem-solving. Based on their answer, you can then teach your general rule, provide positive feedback on what the student said accurately, and ultimately correct any erroneous information. This prototype of learning is best utilized in the clinical setting but also can enhance participant engagement in lectures while maintaining an inviting educational environment. 

Step 5: Summarize 

Lastly, conclude your presentation with at least 3 memorable points. What was the point of the presentation? What message do you want your audience to take with them and apply to clinical care? Reiterating the key points through repetition is crucial for long-term memory. Leave the audience with additional thoughts for exploration and subsequent discussion. How can your work or topic be further translated into additional projects for investigation? If the lecture material contains abundant clinical information beyond 3 points, a handout can be helpful to avoid having learners struggling to keep up with notes. This piece of take-home material can serve as a tool for subsequent study and to stimulate enhanced memory of the subject material provided. A strong concluding message can consolidate and remind learners of the scope of the topic and highlight the vital information that should be retained.

Final Thoughts

In summary, the clinical lecturer provides a unique teaching experience, and all physicians should feel proficient in formulating and delivering an educational lecture. These simple tips that call for the teacher to know and prepare his/her key message to deliver an animated and engaged presentation and then to summarize key findings are suggestions for the utmost transmission of data and ideas for all learners.

Acknowledgment
A special thank you to Joan E. St. Onge, MD (Miami, Florida), for her help providing resources for this topic. 

SAN DIEGO – For patients with type 2 diabetes at high risk of cardiovascular disease, the ultra–long-acting, once-daily basal insulin degludec produced a similar risk of major adverse cardiovascular events as glargine with a significantly lower risk of severe hypoglycemia, new data show.

Nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death occurred in 325 (8.5%) patients on degludec and 356 (9.3%) patients on glargine (hazard ratio, 0.91; 95% confidence interval, 0.78 to 1.06; P = .21) in DEVOTE (the Trial Comparing Cardiovascular Safety of Insulin Degludec versus Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events). Rates of severe hypoglycemia were 4.9% and 6.6%, respectively (P less than .001), investigators reported at the annual scientific sessions of the American Diabetes Association and simultaneously in the New England Journal of Medicine (2017 Jun 12. doi: 10.1056/NEJMoa1615692).

Amy Karon/Frontline Medical News

SAN DIEGO – For patients with type 2 diabetes at high risk of cardiovascular disease, the ultra–long-acting, once-daily basal insulin degludec produced a similar risk of major adverse cardiovascular events as glargine with a significantly lower risk of severe hypoglycemia, new data show.

Nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death occurred in 325 (8.5%) patients on degludec and 356 (9.3%) patients on glargine (hazard ratio, 0.91; 95% confidence interval, 0.78 to 1.06; P = .21) in DEVOTE (the Trial Comparing Cardiovascular Safety of Insulin Degludec versus Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events). Rates of severe hypoglycemia were 4.9% and 6.6%, respectively (P less than .001), investigators reported at the annual scientific sessions of the American Diabetes Association and simultaneously in the New England Journal of Medicine (2017 Jun 12. doi: 10.1056/NEJMoa1615692).

Amy Karon/Frontline Medical News

SAN DIEGO – For patients with type 2 diabetes at high risk of cardiovascular disease, the ultra–long-acting, once-daily basal insulin degludec produced a similar risk of major adverse cardiovascular events as glargine with a significantly lower risk of severe hypoglycemia, new data show.

Nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death occurred in 325 (8.5%) patients on degludec and 356 (9.3%) patients on glargine (hazard ratio, 0.91; 95% confidence interval, 0.78 to 1.06; P = .21) in DEVOTE (the Trial Comparing Cardiovascular Safety of Insulin Degludec versus Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events). Rates of severe hypoglycemia were 4.9% and 6.6%, respectively (P less than .001), investigators reported at the annual scientific sessions of the American Diabetes Association and simultaneously in the New England Journal of Medicine (2017 Jun 12. doi: 10.1056/NEJMoa1615692).

Amy Karon/Frontline Medical News

WASHINGTON – Adding angiotensin II to available vasopressor therapies correlated with significantly improved arterial pressure in patients with catecholamine-resistant vasodilatory shock and less adverse effects, according to a study presented at the recent international conference of the American Thoracic Society.

In a double blind, controlled, phase III study, 70% of 163 patients given angiotensin II reached arterial pressure of at least 75 mm HG or improved by at least 10 mm Hg three hours later, compared with 23.4% of the 158 patients given a placebo (P less than .001).

Those in the angiotensin II group also saw a mean pressure increase of 12.5 mm Hg in the first 3 hours after initiating treatment, compared with 2.9 mm Hg in the placebo group (P less than .001), according to Ashish Khanna, MD, FCCP, of the Cleveland Clinic, and his fellow researchers (N Engl J Med. 2017 May 21. doi: 10.1056/NEJMoa1704154).

Current vasopressor therapies for vasodilatory patients are associated with dangerous side effects and a 30-day mortality rate of more than 50%, which is a major concern for patients who do not have many options to begin with, the researchers noted.

“Treatment options for patients with catecholamine-resistant vasodilatory shock are limited, and the treatments that are available are often associated with side effects,” said Dr. Khanna and his colleagues.

The researchers added the naturally occurring peptide hormone angiotensin II to vasodilatory patients’ treatment regimen in order to “more closely [mimic] natural physiologic responses to shock, which include increased secretion of catecholamines, vasopressin, and RAAS hormones.”

To test the efficacy of angiotensin II, researchers gathered patients with a median age of 64 years and a mean arterial pressure of 66.3 mm Hg.

Sepsis was the predominant cause of shock for 80.7% of the study’s participants.

Patients were injected with either 20 ng/kg of body weight per minute of angiotensin II or an equivalent dose of a placebo until mean arterial pressure reached 75 mm Hg. After 3 hours and 15 minutes of treatment, the dosages were adjusted to keep pressure between 65 and 75 mm Hg for the next 48 hours.

Among patients in the angiotensin II group, 67% of patients were able to decrease angiotensin II and vasopressor doses within 30 minutes of injection, according to researchers.

When researchers measured improvement using the cardiovascular Sequential Organ Failure Assessment, patients in the angiotensin II group saw an average decrease of 1.75 points, compared with 1.28 points in patients in the placebo group (P = .01) 48 hours after treatment.

The Sequential Organ Failure Assessment is scaled from 0-4, with higher scores indicating more severe organ failure.

When measuring for adverse affects, serious effects occurred in 60.7% of the angiotensin II patients, compared with in 67.1% of those in the placebo group.

At the 28-day mark, 75 angiotensin II patients (46.0%) died, compared with 85 patients (53.8%) of the placebo group.

This study was limited by the small sample size, “so the possibility of clinically important side effects attributable to angiotensin II therapy cannot be exuded,” the researches warned.

Also, the follow-up timeline of 28 days, may not have given researchers enough time to uncover the full extent of positive and negative long-term effects associated with angiotensin II.

This study was supported by La Jolla Pharmaceutical, from which multiple researchers reported receiving financial support in the form of personal fees and grants. Two of the researchers reported having patents related to administering angiotensin II and additional patents pending.

[email protected]

On Twitter @eaztweets

WASHINGTON – Adding angiotensin II to available vasopressor therapies correlated with significantly improved arterial pressure in patients with catecholamine-resistant vasodilatory shock and less adverse effects, according to a study presented at the recent international conference of the American Thoracic Society.

In a double blind, controlled, phase III study, 70% of 163 patients given angiotensin II reached arterial pressure of at least 75 mm HG or improved by at least 10 mm Hg three hours later, compared with 23.4% of the 158 patients given a placebo (P less than .001).

Those in the angiotensin II group also saw a mean pressure increase of 12.5 mm Hg in the first 3 hours after initiating treatment, compared with 2.9 mm Hg in the placebo group (P less than .001), according to Ashish Khanna, MD, FCCP, of the Cleveland Clinic, and his fellow researchers (N Engl J Med. 2017 May 21. doi: 10.1056/NEJMoa1704154).

Current vasopressor therapies for vasodilatory patients are associated with dangerous side effects and a 30-day mortality rate of more than 50%, which is a major concern for patients who do not have many options to begin with, the researchers noted.

“Treatment options for patients with catecholamine-resistant vasodilatory shock are limited, and the treatments that are available are often associated with side effects,” said Dr. Khanna and his colleagues.

The researchers added the naturally occurring peptide hormone angiotensin II to vasodilatory patients’ treatment regimen in order to “more closely [mimic] natural physiologic responses to shock, which include increased secretion of catecholamines, vasopressin, and RAAS hormones.”

To test the efficacy of angiotensin II, researchers gathered patients with a median age of 64 years and a mean arterial pressure of 66.3 mm Hg.

Sepsis was the predominant cause of shock for 80.7% of the study’s participants.

Patients were injected with either 20 ng/kg of body weight per minute of angiotensin II or an equivalent dose of a placebo until mean arterial pressure reached 75 mm Hg. After 3 hours and 15 minutes of treatment, the dosages were adjusted to keep pressure between 65 and 75 mm Hg for the next 48 hours.

Among patients in the angiotensin II group, 67% of patients were able to decrease angiotensin II and vasopressor doses within 30 minutes of injection, according to researchers.

When researchers measured improvement using the cardiovascular Sequential Organ Failure Assessment, patients in the angiotensin II group saw an average decrease of 1.75 points, compared with 1.28 points in patients in the placebo group (P = .01) 48 hours after treatment.

The Sequential Organ Failure Assessment is scaled from 0-4, with higher scores indicating more severe organ failure.

When measuring for adverse affects, serious effects occurred in 60.7% of the angiotensin II patients, compared with in 67.1% of those in the placebo group.

At the 28-day mark, 75 angiotensin II patients (46.0%) died, compared with 85 patients (53.8%) of the placebo group.

This study was limited by the small sample size, “so the possibility of clinically important side effects attributable to angiotensin II therapy cannot be exuded,” the researches warned.

Also, the follow-up timeline of 28 days, may not have given researchers enough time to uncover the full extent of positive and negative long-term effects associated with angiotensin II.

This study was supported by La Jolla Pharmaceutical, from which multiple researchers reported receiving financial support in the form of personal fees and grants. Two of the researchers reported having patents related to administering angiotensin II and additional patents pending.

[email protected]

On Twitter @eaztweets

WASHINGTON – Adding angiotensin II to available vasopressor therapies correlated with significantly improved arterial pressure in patients with catecholamine-resistant vasodilatory shock and less adverse effects, according to a study presented at the recent international conference of the American Thoracic Society.

In a double blind, controlled, phase III study, 70% of 163 patients given angiotensin II reached arterial pressure of at least 75 mm HG or improved by at least 10 mm Hg three hours later, compared with 23.4% of the 158 patients given a placebo (P less than .001).

Those in the angiotensin II group also saw a mean pressure increase of 12.5 mm Hg in the first 3 hours after initiating treatment, compared with 2.9 mm Hg in the placebo group (P less than .001), according to Ashish Khanna, MD, FCCP, of the Cleveland Clinic, and his fellow researchers (N Engl J Med. 2017 May 21. doi: 10.1056/NEJMoa1704154).

Current vasopressor therapies for vasodilatory patients are associated with dangerous side effects and a 30-day mortality rate of more than 50%, which is a major concern for patients who do not have many options to begin with, the researchers noted.

“Treatment options for patients with catecholamine-resistant vasodilatory shock are limited, and the treatments that are available are often associated with side effects,” said Dr. Khanna and his colleagues.

The researchers added the naturally occurring peptide hormone angiotensin II to vasodilatory patients’ treatment regimen in order to “more closely [mimic] natural physiologic responses to shock, which include increased secretion of catecholamines, vasopressin, and RAAS hormones.”

To test the efficacy of angiotensin II, researchers gathered patients with a median age of 64 years and a mean arterial pressure of 66.3 mm Hg.

Sepsis was the predominant cause of shock for 80.7% of the study’s participants.

Patients were injected with either 20 ng/kg of body weight per minute of angiotensin II or an equivalent dose of a placebo until mean arterial pressure reached 75 mm Hg. After 3 hours and 15 minutes of treatment, the dosages were adjusted to keep pressure between 65 and 75 mm Hg for the next 48 hours.

Among patients in the angiotensin II group, 67% of patients were able to decrease angiotensin II and vasopressor doses within 30 minutes of injection, according to researchers.

When researchers measured improvement using the cardiovascular Sequential Organ Failure Assessment, patients in the angiotensin II group saw an average decrease of 1.75 points, compared with 1.28 points in patients in the placebo group (P = .01) 48 hours after treatment.

The Sequential Organ Failure Assessment is scaled from 0-4, with higher scores indicating more severe organ failure.

When measuring for adverse affects, serious effects occurred in 60.7% of the angiotensin II patients, compared with in 67.1% of those in the placebo group.

At the 28-day mark, 75 angiotensin II patients (46.0%) died, compared with 85 patients (53.8%) of the placebo group.

This study was limited by the small sample size, “so the possibility of clinically important side effects attributable to angiotensin II therapy cannot be exuded,” the researches warned.

Also, the follow-up timeline of 28 days, may not have given researchers enough time to uncover the full extent of positive and negative long-term effects associated with angiotensin II.

This study was supported by La Jolla Pharmaceutical, from which multiple researchers reported receiving financial support in the form of personal fees and grants. Two of the researchers reported having patents related to administering angiotensin II and additional patents pending.

[email protected]

On Twitter @eaztweets

The VA and the Department of Energy (DoE) have formed a new partnership focused on secure analysis of “big data.” The VA-DoE Big Data Science Initiative will use digital health and genomic data from the Million Veteran Program (MVP), the VA’s electronic health records system, DoD, Centers for Medicare and Medicaid Services, and the CDC’s National Death Index.

The partnership is based in DoE’s National Laboratory system, one of the world’s top resources for supercomputing, where machines are capable of millions of billions of calculations per second. The partnership will allow thousands of researchers access to this unprecedented data resource over time in a secure environment, said VA Secretary David J. Shulkin, MD.

An initial suite of specific studies is already being planned, the VA says. One group of researchers will build algorithms to generate “highly tailored” risk scores for suicide, which could help VA clinicians and researchers predict which patients are at highest risk and evaluate prevention strategies.

Other projects include one to find new ways to distinguish lethal from nonlethal prostate cancer and another to determine which risk factors best predict certain forms of cardiovascular disease.

“The transformative science that will be developed through this partnership,” Shulkin says, “will improve health care for veterans and all Americans.”

The VA and the Department of Energy (DoE) have formed a new partnership focused on secure analysis of “big data.” The VA-DoE Big Data Science Initiative will use digital health and genomic data from the Million Veteran Program (MVP), the VA’s electronic health records system, DoD, Centers for Medicare and Medicaid Services, and the CDC’s National Death Index.

The partnership is based in DoE’s National Laboratory system, one of the world’s top resources for supercomputing, where machines are capable of millions of billions of calculations per second. The partnership will allow thousands of researchers access to this unprecedented data resource over time in a secure environment, said VA Secretary David J. Shulkin, MD.

An initial suite of specific studies is already being planned, the VA says. One group of researchers will build algorithms to generate “highly tailored” risk scores for suicide, which could help VA clinicians and researchers predict which patients are at highest risk and evaluate prevention strategies.

Other projects include one to find new ways to distinguish lethal from nonlethal prostate cancer and another to determine which risk factors best predict certain forms of cardiovascular disease.

“The transformative science that will be developed through this partnership,” Shulkin says, “will improve health care for veterans and all Americans.”

The VA and the Department of Energy (DoE) have formed a new partnership focused on secure analysis of “big data.” The VA-DoE Big Data Science Initiative will use digital health and genomic data from the Million Veteran Program (MVP), the VA’s electronic health records system, DoD, Centers for Medicare and Medicaid Services, and the CDC’s National Death Index.

The partnership is based in DoE’s National Laboratory system, one of the world’s top resources for supercomputing, where machines are capable of millions of billions of calculations per second. The partnership will allow thousands of researchers access to this unprecedented data resource over time in a secure environment, said VA Secretary David J. Shulkin, MD.

An initial suite of specific studies is already being planned, the VA says. One group of researchers will build algorithms to generate “highly tailored” risk scores for suicide, which could help VA clinicians and researchers predict which patients are at highest risk and evaluate prevention strategies.

Other projects include one to find new ways to distinguish lethal from nonlethal prostate cancer and another to determine which risk factors best predict certain forms of cardiovascular disease.

“The transformative science that will be developed through this partnership,” Shulkin says, “will improve health care for veterans and all Americans.”

Photo courtesy of Merck

Merck announced that it is pausing enrollment onto 2 phase 3 trials of pembrolizumab (Keytruda®) in combination with other agents to treat multiple myeloma (MM).

An external Data Monitoring Committee recommended the trial be interrupted “to allow for additional information be collected to better understand more reports of death” in the pembrolizumab groups in the KEYNOTE-183 and KEYNOTE-185 trials.

Patients currently enrolled on the trials can continue to receive treatment. Other pembrolizumab trials are continuing without changes.

Merck in its statement did not disclose the number of deaths nor provide any other details on the deaths.

Pembrolizumab is a humanized monoclonal antibody that blocks interaction between the programmed cell death protein 1 (PD-1) and its receptor ligands, PD-L1 and PD-L2.

The US Food & Drug Administration approved pembrolizumab to treat unresectable or metastatic melanoma after ipilimumab treatment.

Pembrolizumab has also been approved to treat non-small cell lung cancer, head and neck squamous cell cancer, classical Hodgkin lymphoma, urothelial carcinoma, and microsatellite instability-high solid tumors.

KEYNOTE-183 (NCT02576977), which has an estimated enrollment of 300 patients, is comparing the combination of pembrolizumab, pomalidomide, and low-dose dexamethasone to pomalidomide and low-dose dexamethasone alone in patients with relapsed or refractory MM who have undergone at least 2 lines of prior therapy.

KEYNOTE-185 (NCT02579863), which has an estimated enrollment of 640 patients, is comparing the combination of pembrolizumab, lenalidomide, and low-dose dexamethasone to lenalidomide and low-dose desamethasone alone in patients with newly diagnosed and treatment-native MM who are ineligible for autologous stem cell transplant.

The comparator agents pomalidomide (Pomalyst®) and lenalidomide (Revlimid®) are products of Celgene Corporation. 

Photo courtesy of Merck

Merck announced that it is pausing enrollment onto 2 phase 3 trials of pembrolizumab (Keytruda®) in combination with other agents to treat multiple myeloma (MM).

An external Data Monitoring Committee recommended the trial be interrupted “to allow for additional information be collected to better understand more reports of death” in the pembrolizumab groups in the KEYNOTE-183 and KEYNOTE-185 trials.

Patients currently enrolled on the trials can continue to receive treatment. Other pembrolizumab trials are continuing without changes.

Merck in its statement did not disclose the number of deaths nor provide any other details on the deaths.

Pembrolizumab is a humanized monoclonal antibody that blocks interaction between the programmed cell death protein 1 (PD-1) and its receptor ligands, PD-L1 and PD-L2.

The US Food & Drug Administration approved pembrolizumab to treat unresectable or metastatic melanoma after ipilimumab treatment.

Pembrolizumab has also been approved to treat non-small cell lung cancer, head and neck squamous cell cancer, classical Hodgkin lymphoma, urothelial carcinoma, and microsatellite instability-high solid tumors.

KEYNOTE-183 (NCT02576977), which has an estimated enrollment of 300 patients, is comparing the combination of pembrolizumab, pomalidomide, and low-dose dexamethasone to pomalidomide and low-dose dexamethasone alone in patients with relapsed or refractory MM who have undergone at least 2 lines of prior therapy.

KEYNOTE-185 (NCT02579863), which has an estimated enrollment of 640 patients, is comparing the combination of pembrolizumab, lenalidomide, and low-dose dexamethasone to lenalidomide and low-dose desamethasone alone in patients with newly diagnosed and treatment-native MM who are ineligible for autologous stem cell transplant.

The comparator agents pomalidomide (Pomalyst®) and lenalidomide (Revlimid®) are products of Celgene Corporation. 

Photo courtesy of Merck

Merck announced that it is pausing enrollment onto 2 phase 3 trials of pembrolizumab (Keytruda®) in combination with other agents to treat multiple myeloma (MM).

An external Data Monitoring Committee recommended the trial be interrupted “to allow for additional information be collected to better understand more reports of death” in the pembrolizumab groups in the KEYNOTE-183 and KEYNOTE-185 trials.

Patients currently enrolled on the trials can continue to receive treatment. Other pembrolizumab trials are continuing without changes.

Merck in its statement did not disclose the number of deaths nor provide any other details on the deaths.

Pembrolizumab is a humanized monoclonal antibody that blocks interaction between the programmed cell death protein 1 (PD-1) and its receptor ligands, PD-L1 and PD-L2.

The US Food & Drug Administration approved pembrolizumab to treat unresectable or metastatic melanoma after ipilimumab treatment.

Pembrolizumab has also been approved to treat non-small cell lung cancer, head and neck squamous cell cancer, classical Hodgkin lymphoma, urothelial carcinoma, and microsatellite instability-high solid tumors.

KEYNOTE-183 (NCT02576977), which has an estimated enrollment of 300 patients, is comparing the combination of pembrolizumab, pomalidomide, and low-dose dexamethasone to pomalidomide and low-dose dexamethasone alone in patients with relapsed or refractory MM who have undergone at least 2 lines of prior therapy.

KEYNOTE-185 (NCT02579863), which has an estimated enrollment of 640 patients, is comparing the combination of pembrolizumab, lenalidomide, and low-dose dexamethasone to lenalidomide and low-dose desamethasone alone in patients with newly diagnosed and treatment-native MM who are ineligible for autologous stem cell transplant.

The comparator agents pomalidomide (Pomalyst®) and lenalidomide (Revlimid®) are products of Celgene Corporation. 

Mesenchymal stromal cells

Researchers report that infusions of bone marrow-derived mesenchymal stromal cells (BM-MSCs) may be a treatment option for patients with aplastic anemia (AA) who are refractory to immunosuppressive therapy (IST).

They conducted a phase 2, non-comparative multicenter study to assess the safety and efficacy of this approach and found that after 12 months, 28.4% of patients responded, with 6.8% achieving a complete response (CR) and 21.6% a partial response (PR).

The trial involved 74 patients at 7 centers in China. The research team reported its findings in Stem Cells Translational Medicine.

About 30% to 40% of patients with severe AA (sAA) don’t respond well to IST and continue to have abnormally low levels of red blood cells, white blood cells, and platelets.

The benefit of treatment with BM-MSCs is they support hematopoiesis, express low levels of major histocompatibility (MHC)-I, and lack expression of MHC-II surface molecules.

And BM-MSCs have been reported to cure diseases, including graft-versus-host disease, arthritis, lupus, and other immune and non-immune disorders.

The current study, led by Yan Pang, MD, and Yang Xiao, MD, PhD, of Guangzhou General Hospital of Guangzhou Military Command in China, is based on their previous data evaluating intravenous administration of MSCs from a related donor in 18 patients with refractory AA.

This earlier data showed that 33% of patients with AA refractory to IST achieved a CR or PR to BM-MSC treatment.

So the team undertook to further investigate the use of BM-MSCs in AA.

Study design

Each of the 74 patients received 4 doses of BM-MSCs over a period of 4 weeks. If patients responded after the first month, they continued to receive 4 doses.

Investigators obtained the BM-MSCs from 74 healthy donors—48 males and 26 females. Forty were related donors, 27 haploidentical donors, and 7 unrelated donors.

Patients with AA by standard criteria had to be 16 years or older, had an incomplete response to antithymocyte globulin (ATG) and cyclosporine for at leas 6 months or cyclosporine alone for at least 12 months, did not have a donor available for bone marrow transplantation, and had at least one of the following: hemoglobin <70 g/L, neutrophilic granulocytes <1 × 10⁹/L, or platelet count <30 × 10⁹/L.

Almost half the patients (47%) were between 20 and 40 years, 54% were male, and 32% had severe aplastic anemia.

Patients’ previous therapy for aplastic anemia included cyclosporine and andriol (65%) cyclosporine and ATG (19%), and cyclosporine (16%).

Patients could continue cyclosporine, but no immunosuppressive agents were permitted.

Fifty-three patients (71.6%) completed 1 course of therapy, and 21 patients (18.4%) completed 2 courses.

Response

 At 1 year, the overall response rate was 28.4% (n=21) and the PR rate was 21.6% (n=16).

The median time to a leukocyte response was 19 days (range, 11 – 29), to an erythrocyte response 17 days (range, 12 – 25), and to a megakaryocyte response 31 days (range, 26 – 84).

Ten of the patients with hematologic response had normalization of cellularity for more than 1 year.

The median follow-up among survivors was 17 months (range, 3 – 24). The 2-year overall survival was 87.8%.

Three patients progressed to myelodysplasia, 1 with refractory anemia with excess blasts (RAEB)-I and 2 with RAEB-II.

The median time to progression was 11 months (range, 8 – 12).

Nine patients died, all of whom had severe AA. One patient with RAEB-II died of disease progression, two patients died of intracranial hemorrhage, and six patients died of serious infection.

 Safety

Adverse events included grade 1 (n=5) and grade 2 (n=2) fever. Two of these patients also had grade 1 headache.

The investigators observed no other adverse events.

Response predictors

The investigators determined that 2 factors predicted response in patients: prior treatment with antithymocyte globulin (ATG) and absence of infection throughout the treatment.

The odds ratio for patients treated with ATG was 1.41 (95% CI: -0.50, 3.31) and for patients without infection, 2.19 (95% CI: 0.50, 3.87).

“Our study strongly indicates that MSC infusion is a promising therapy for severe AA," Dr Pang said, “but improved MSC cultures in vitro and the MSC doses need further study to maximize their therapeutic potential." 

Mesenchymal stromal cells

Researchers report that infusions of bone marrow-derived mesenchymal stromal cells (BM-MSCs) may be a treatment option for patients with aplastic anemia (AA) who are refractory to immunosuppressive therapy (IST).

They conducted a phase 2, non-comparative multicenter study to assess the safety and efficacy of this approach and found that after 12 months, 28.4% of patients responded, with 6.8% achieving a complete response (CR) and 21.6% a partial response (PR).

The trial involved 74 patients at 7 centers in China. The research team reported its findings in Stem Cells Translational Medicine.

About 30% to 40% of patients with severe AA (sAA) don’t respond well to IST and continue to have abnormally low levels of red blood cells, white blood cells, and platelets.

The benefit of treatment with BM-MSCs is they support hematopoiesis, express low levels of major histocompatibility (MHC)-I, and lack expression of MHC-II surface molecules.

And BM-MSCs have been reported to cure diseases, including graft-versus-host disease, arthritis, lupus, and other immune and non-immune disorders.

The current study, led by Yan Pang, MD, and Yang Xiao, MD, PhD, of Guangzhou General Hospital of Guangzhou Military Command in China, is based on their previous data evaluating intravenous administration of MSCs from a related donor in 18 patients with refractory AA.

This earlier data showed that 33% of patients with AA refractory to IST achieved a CR or PR to BM-MSC treatment.

So the team undertook to further investigate the use of BM-MSCs in AA.

Study design

Each of the 74 patients received 4 doses of BM-MSCs over a period of 4 weeks. If patients responded after the first month, they continued to receive 4 doses.

Investigators obtained the BM-MSCs from 74 healthy donors—48 males and 26 females. Forty were related donors, 27 haploidentical donors, and 7 unrelated donors.

Patients with AA by standard criteria had to be 16 years or older, had an incomplete response to antithymocyte globulin (ATG) and cyclosporine for at leas 6 months or cyclosporine alone for at least 12 months, did not have a donor available for bone marrow transplantation, and had at least one of the following: hemoglobin <70 g/L, neutrophilic granulocytes <1 × 10⁹/L, or platelet count <30 × 10⁹/L.

Almost half the patients (47%) were between 20 and 40 years, 54% were male, and 32% had severe aplastic anemia.

Patients’ previous therapy for aplastic anemia included cyclosporine and andriol (65%) cyclosporine and ATG (19%), and cyclosporine (16%).

Patients could continue cyclosporine, but no immunosuppressive agents were permitted.

Fifty-three patients (71.6%) completed 1 course of therapy, and 21 patients (18.4%) completed 2 courses.

Response

 At 1 year, the overall response rate was 28.4% (n=21) and the PR rate was 21.6% (n=16).

The median time to a leukocyte response was 19 days (range, 11 – 29), to an erythrocyte response 17 days (range, 12 – 25), and to a megakaryocyte response 31 days (range, 26 – 84).

Ten of the patients with hematologic response had normalization of cellularity for more than 1 year.

The median follow-up among survivors was 17 months (range, 3 – 24). The 2-year overall survival was 87.8%.

Three patients progressed to myelodysplasia, 1 with refractory anemia with excess blasts (RAEB)-I and 2 with RAEB-II.

The median time to progression was 11 months (range, 8 – 12).

Nine patients died, all of whom had severe AA. One patient with RAEB-II died of disease progression, two patients died of intracranial hemorrhage, and six patients died of serious infection.

 Safety

Adverse events included grade 1 (n=5) and grade 2 (n=2) fever. Two of these patients also had grade 1 headache.

The investigators observed no other adverse events.

Response predictors

The investigators determined that 2 factors predicted response in patients: prior treatment with antithymocyte globulin (ATG) and absence of infection throughout the treatment.

The odds ratio for patients treated with ATG was 1.41 (95% CI: -0.50, 3.31) and for patients without infection, 2.19 (95% CI: 0.50, 3.87).

“Our study strongly indicates that MSC infusion is a promising therapy for severe AA," Dr Pang said, “but improved MSC cultures in vitro and the MSC doses need further study to maximize their therapeutic potential." 

Mesenchymal stromal cells

Researchers report that infusions of bone marrow-derived mesenchymal stromal cells (BM-MSCs) may be a treatment option for patients with aplastic anemia (AA) who are refractory to immunosuppressive therapy (IST).

They conducted a phase 2, non-comparative multicenter study to assess the safety and efficacy of this approach and found that after 12 months, 28.4% of patients responded, with 6.8% achieving a complete response (CR) and 21.6% a partial response (PR).

The trial involved 74 patients at 7 centers in China. The research team reported its findings in Stem Cells Translational Medicine.

About 30% to 40% of patients with severe AA (sAA) don’t respond well to IST and continue to have abnormally low levels of red blood cells, white blood cells, and platelets.

The benefit of treatment with BM-MSCs is they support hematopoiesis, express low levels of major histocompatibility (MHC)-I, and lack expression of MHC-II surface molecules.

And BM-MSCs have been reported to cure diseases, including graft-versus-host disease, arthritis, lupus, and other immune and non-immune disorders.

The current study, led by Yan Pang, MD, and Yang Xiao, MD, PhD, of Guangzhou General Hospital of Guangzhou Military Command in China, is based on their previous data evaluating intravenous administration of MSCs from a related donor in 18 patients with refractory AA.

This earlier data showed that 33% of patients with AA refractory to IST achieved a CR or PR to BM-MSC treatment.

So the team undertook to further investigate the use of BM-MSCs in AA.

Study design

Each of the 74 patients received 4 doses of BM-MSCs over a period of 4 weeks. If patients responded after the first month, they continued to receive 4 doses.

Investigators obtained the BM-MSCs from 74 healthy donors—48 males and 26 females. Forty were related donors, 27 haploidentical donors, and 7 unrelated donors.

Patients with AA by standard criteria had to be 16 years or older, had an incomplete response to antithymocyte globulin (ATG) and cyclosporine for at leas 6 months or cyclosporine alone for at least 12 months, did not have a donor available for bone marrow transplantation, and had at least one of the following: hemoglobin <70 g/L, neutrophilic granulocytes <1 × 10⁹/L, or platelet count <30 × 10⁹/L.

Almost half the patients (47%) were between 20 and 40 years, 54% were male, and 32% had severe aplastic anemia.

Patients’ previous therapy for aplastic anemia included cyclosporine and andriol (65%) cyclosporine and ATG (19%), and cyclosporine (16%).

Patients could continue cyclosporine, but no immunosuppressive agents were permitted.

Fifty-three patients (71.6%) completed 1 course of therapy, and 21 patients (18.4%) completed 2 courses.

Response

 At 1 year, the overall response rate was 28.4% (n=21) and the PR rate was 21.6% (n=16).

The median time to a leukocyte response was 19 days (range, 11 – 29), to an erythrocyte response 17 days (range, 12 – 25), and to a megakaryocyte response 31 days (range, 26 – 84).

Ten of the patients with hematologic response had normalization of cellularity for more than 1 year.

The median follow-up among survivors was 17 months (range, 3 – 24). The 2-year overall survival was 87.8%.

Three patients progressed to myelodysplasia, 1 with refractory anemia with excess blasts (RAEB)-I and 2 with RAEB-II.

The median time to progression was 11 months (range, 8 – 12).

Nine patients died, all of whom had severe AA. One patient with RAEB-II died of disease progression, two patients died of intracranial hemorrhage, and six patients died of serious infection.

 Safety

Adverse events included grade 1 (n=5) and grade 2 (n=2) fever. Two of these patients also had grade 1 headache.

The investigators observed no other adverse events.

Response predictors

The investigators determined that 2 factors predicted response in patients: prior treatment with antithymocyte globulin (ATG) and absence of infection throughout the treatment.

The odds ratio for patients treated with ATG was 1.41 (95% CI: -0.50, 3.31) and for patients without infection, 2.19 (95% CI: 0.50, 3.87).

“Our study strongly indicates that MSC infusion is a promising therapy for severe AA," Dr Pang said, “but improved MSC cultures in vitro and the MSC doses need further study to maximize their therapeutic potential."