From the Editor

I have nothing to disclose.

That is the first line on my second slide in just about every talk I give. I have no financial conflicts of interest. I no longer accept meals from pharmaceutical companies, I no longer conduct pharmaceutical company sponsored research, and I no longer give talks that include honoraria from pharmaceutical companies. I turn down payments from pharmaceutical companies when I participate in drug-monitoring safety boards and advisory committees. I do not have a financial conflict of interest.

Or do I?

I almost gave up when they asked me to provide a Physician Taxonomy Code. It took me a long time to find it. For those interested, the code for Hematology is 207RH0000X. With that code entered in the right box, I was only two pages away from being registered and ready to open the dispute. Failure hit me like a lake effect snow storm. Despite my diligence, I was not “vetted” and could not file a dispute. I must have done something wrong and cannot seem to investigate the payment further, but I’m sure the New York Times could.

Now, I don’t know if I have anything to disclose or not. I do know that I have to investigate my payment the best I can, that I have to disclose it if it is real, and that I have to check Open Payments every so often to make sure I am not surprised by an investigative journalist’s report in the future. Add these to the pantheon of onerous requirements for a successful academic career.

Onerous or not, we have an obligation to disclose our financial ties to industry no matter how entangled we are. Many wear their entanglements as a badge of honor on slides highlighting a long list of conflicts. One speaker joked that she had so many conflicts that she had no conflicts. Clearly, much like alarm fatigue, the constant display of financial conflict of interest disclosures rarely raises red flags in an audience of peers. To an audience of interested lay persons, though, those conflicts may be very important and relevant.

It is our duty to accurately account for and report them no matter the difficulty in doing so. Failure to do so can carry tragic consequences.

Dr. Kalaycio is editor in chief of Hematology News. He chairs the department of hematologic oncology and blood disorders at Cleveland Clinic Taussig Cancer Institute. Contact him at [email protected].

I have nothing to disclose.

That is the first line on my second slide in just about every talk I give. I have no financial conflicts of interest. I no longer accept meals from pharmaceutical companies, I no longer conduct pharmaceutical company sponsored research, and I no longer give talks that include honoraria from pharmaceutical companies. I turn down payments from pharmaceutical companies when I participate in drug-monitoring safety boards and advisory committees. I do not have a financial conflict of interest.

Or do I?

I almost gave up when they asked me to provide a Physician Taxonomy Code. It took me a long time to find it. For those interested, the code for Hematology is 207RH0000X. With that code entered in the right box, I was only two pages away from being registered and ready to open the dispute. Failure hit me like a lake effect snow storm. Despite my diligence, I was not “vetted” and could not file a dispute. I must have done something wrong and cannot seem to investigate the payment further, but I’m sure the New York Times could.

Now, I don’t know if I have anything to disclose or not. I do know that I have to investigate my payment the best I can, that I have to disclose it if it is real, and that I have to check Open Payments every so often to make sure I am not surprised by an investigative journalist’s report in the future. Add these to the pantheon of onerous requirements for a successful academic career.

Onerous or not, we have an obligation to disclose our financial ties to industry no matter how entangled we are. Many wear their entanglements as a badge of honor on slides highlighting a long list of conflicts. One speaker joked that she had so many conflicts that she had no conflicts. Clearly, much like alarm fatigue, the constant display of financial conflict of interest disclosures rarely raises red flags in an audience of peers. To an audience of interested lay persons, though, those conflicts may be very important and relevant.

It is our duty to accurately account for and report them no matter the difficulty in doing so. Failure to do so can carry tragic consequences.

Dr. Kalaycio is editor in chief of Hematology News. He chairs the department of hematologic oncology and blood disorders at Cleveland Clinic Taussig Cancer Institute. Contact him at [email protected].

I have nothing to disclose.

That is the first line on my second slide in just about every talk I give. I have no financial conflicts of interest. I no longer accept meals from pharmaceutical companies, I no longer conduct pharmaceutical company sponsored research, and I no longer give talks that include honoraria from pharmaceutical companies. I turn down payments from pharmaceutical companies when I participate in drug-monitoring safety boards and advisory committees. I do not have a financial conflict of interest.

Or do I?

I almost gave up when they asked me to provide a Physician Taxonomy Code. It took me a long time to find it. For those interested, the code for Hematology is 207RH0000X. With that code entered in the right box, I was only two pages away from being registered and ready to open the dispute. Failure hit me like a lake effect snow storm. Despite my diligence, I was not “vetted” and could not file a dispute. I must have done something wrong and cannot seem to investigate the payment further, but I’m sure the New York Times could.

Now, I don’t know if I have anything to disclose or not. I do know that I have to investigate my payment the best I can, that I have to disclose it if it is real, and that I have to check Open Payments every so often to make sure I am not surprised by an investigative journalist’s report in the future. Add these to the pantheon of onerous requirements for a successful academic career.

Onerous or not, we have an obligation to disclose our financial ties to industry no matter how entangled we are. Many wear their entanglements as a badge of honor on slides highlighting a long list of conflicts. One speaker joked that she had so many conflicts that she had no conflicts. Clearly, much like alarm fatigue, the constant display of financial conflict of interest disclosures rarely raises red flags in an audience of peers. To an audience of interested lay persons, though, those conflicts may be very important and relevant.

It is our duty to accurately account for and report them no matter the difficulty in doing so. Failure to do so can carry tragic consequences.

Dr. Kalaycio is editor in chief of Hematology News. He chairs the department of hematologic oncology and blood disorders at Cleveland Clinic Taussig Cancer Institute. Contact him at [email protected].

Surgeons have a time-honored institution of reflection, learning, and responsibility in the Morbidity & Mortality conference. The M&M is unique in the medical profession and we should look critically at efforts by hospitals and bureaucracies to change its character and its purpose.

A story in this issue (“Little overlap between surgical M&M and AHRQ” on adverse events, p. xx) covers a published study (Anderson J et al. J Am Coll Surg. 2018 Jul 5. doi: 10.1016/j.jamcollsurg.2018.06.008) of the ways in which surgeon-reported M&M cases do (but mostly, do not) overlap with those captured in the ubiquitous Patient Safety Indicators (PSIs).

I am reminded once again of the long road we have traveled from the M&M conference of my student and resident days in the 1970s to today’s version of this event.

At our institution, the M&M has evolved over the years to serve not only an educational venue from which all in attendance learn from the misadventures of others and (hopefully) avoid similar errors in the future, but also as a component of the institution’s overall patient safety and quality improvement program. The authors point out the inherent difference between the clinician-generated M&M cases, which may possess selection bias in the cases they identify as complications, and the strictly defined PSIs that are captured from an administrative database and often include cases overlooked by the clinicians as not relevant to the surgical M&M process.

Both kinds of data are valuable, but for surgeons, the M&M is the one venue where they can focus in the company of their colleagues on those instances where the best intentions go off the rails: erroneous decisions, faulty assessments, and unanticipated complications.

The surgical M&M conference traces its origins to the admirable practice of early 20th century Boston surgeon Ernest Codman, who tracked the treatment outcome of all of his patients on “End Result Cards” for at least a year with the goal of identifying errors to improve the care of his future patients. He established the first M&M conference at Harvard and was one of the founders of the American College of Surgeons and the forerunner of the Joint Commission. His idea that surgeon and hospital outcomes should be made public so that patients could make an informed choice about where and from whom to seek care was, however, vigorously resisted by Harvard and Dr. Codman lost his privileges there.

I would offer that the M&M conference and the PSIs are apples and oranges: both good, but different. Each serves a different purpose. But too much integration of the PSI into the M&M format could end up creating a formulaic adverse events conference that answers to bureaucratic needs of the hospital, but loses some of its value as a forum for learning.

It is worth reflecting on how and why the traditional M&M has such value to surgeons.

To begin with, the quality of the leadership matters. A good leader knows how to avoid blaming, shaming, or embarrassing the presenter, who likely feels bad enough about the complication without being tortured about it. The goal is that all salient factors that contributed to the complication are elicited and that everyone present comes away from the conference armed with alternative ways to prevent a repeat of the same complication.

As a resident I learned more at the Saturday morning M&M than I did at any other conference. I was there every Saturday morning almost without fail for 15 years as a medical student, resident, and faculty member. There I learned not only how to avoid errors and benefit from the accumulated wisdom of many gray hairs in the audience, but also how to present an embarrassing complication both honestly and even with some self-deprecating humor.

Chief residents such as Don Trunkey, Brent Eastman, and Theodore Schrock were gifted in being accountable for mistakes while simultaneously deflecting ire with some well-chosen props. I remember one vivid example: Ted Schrock stepping up to the podium to present a “case gone bad” while holding a garbage-can lid in front of his chest like a shield, ready to defend himself. I don’t remember the case, but the picture is still etched in my mind 45 years later.

Our chairman, Dr. J. Englebert Dunphy, was a master at zeroing in on the critical errors in decision-making or operative conduct that had led to a poor outcome. When the presenter was honest and well-meaning but lacking in sophisticated insight, Dr. Dunphy would calmly ask probing questions that guided the resident to understand why a complication had occurred and how it might have been avoided. If the complication was exceptionally egregious, or the resident was not forthright or was evasive in his “mea culpa,” Dr. Dunphy would turn to one of his staunch faculty allies in the front row and inquire, “Brodie, what do you think about that?” to which Brodie Stephens would typically reply, “Bert, I thought we were here to CURE disease, not CAUSE it!” (To add some colorful football lore to the story, Howard Brodie Stephens was the All-American end who caught a 53-yard pass from “Brick” Muller in the 1921 Rose Bowl victory of Cal Berkeley over Ohio State, the Pacific Coast Conference’s last win against a Big Ten team until 1953.)

Certain resident shortcomings were sure to raise Dr. Dunphy’s ire. These included failing to take responsibility for your mistake and attempting to blame the error on someone else or on another discipline or not adequately supervising an intern or junior resident if you were the chief resident. The latter crime was the subject of one of the most clever and resourceful chief resident M&M presentations of all time, that of past ACS President Brent Eastman as his final presentation from his vascular surgery rotation, the last of his chief year. This one took some moxie, considerable preparation, and the involvement of colleagues near and far. Brent enlisted his good friend and later distinguished cardiac surgeon Dr. Larry Cohn, then junior faculty at Harvard, to find a list of Dr. Dunphy’s complications while he was a resident in Boston in the 1930s. Although records were no longer available, Dr. Cohn mentioned the issue to Dr. Hartwell Harrison, who had been chief resident at the Peter Bent Brigham Hospital when Dr. Dunphy was a junior resident. Dr. Harrison remembered a case that Dr. Dunphy had performed in the outpatient clinic without supervision in which he encountered uncontrolled bleeding.

Armed with the perfect case to present, Brent coached Dr. Edwin (Jack) Wylie to be his “plant” in the audience. At M&M, Brent sheepishly admitted that the case he had to present was that of an unsupervised junior resident who incurred uncontrolled bleeding in the outpatient setting. On cue, Dr. Wylie asked, “Who the hell WAS that resident?” Dr. Eastman then shuffled through his papers to find the correct sheet and announced, “Dr. John E. Dunphy, Peter Bent Brigham Hospital, 1937.” The room exploded in uproarious laughter, joined heartily by Dr. Dunphy.

That was then, and this is now. I can’t envision such a spectacle ever occurring these days. The M&M conference of 2018 has become far more standardized and endowed with greater scientific rigor. Its evolution has likely made M&M more precise and valuable as an educational tool for surgeons to learn from the mistakes of others, but of course, it has lost an element of surprise and hilarity that kept all of us sleep-deprived residents awake and alert. The lessons learned from the traditional M&M lasted this surgeon’s lifetime, and we should consider preserving some of the give-and-take, admission of failure, and reflection that made the M&M so unforgettable.
 

Dr. Deveney is professor of surgery and vice chair of education in the department of surgery at Oregon Health & Science University, Portland. She is the coeditor of ACS Surgery News.

Surgeons have a time-honored institution of reflection, learning, and responsibility in the Morbidity & Mortality conference. The M&M is unique in the medical profession and we should look critically at efforts by hospitals and bureaucracies to change its character and its purpose.

A story in this issue (“Little overlap between surgical M&M and AHRQ” on adverse events, p. xx) covers a published study (Anderson J et al. J Am Coll Surg. 2018 Jul 5. doi: 10.1016/j.jamcollsurg.2018.06.008) of the ways in which surgeon-reported M&M cases do (but mostly, do not) overlap with those captured in the ubiquitous Patient Safety Indicators (PSIs).

I am reminded once again of the long road we have traveled from the M&M conference of my student and resident days in the 1970s to today’s version of this event.

At our institution, the M&M has evolved over the years to serve not only an educational venue from which all in attendance learn from the misadventures of others and (hopefully) avoid similar errors in the future, but also as a component of the institution’s overall patient safety and quality improvement program. The authors point out the inherent difference between the clinician-generated M&M cases, which may possess selection bias in the cases they identify as complications, and the strictly defined PSIs that are captured from an administrative database and often include cases overlooked by the clinicians as not relevant to the surgical M&M process.

Both kinds of data are valuable, but for surgeons, the M&M is the one venue where they can focus in the company of their colleagues on those instances where the best intentions go off the rails: erroneous decisions, faulty assessments, and unanticipated complications.

The surgical M&M conference traces its origins to the admirable practice of early 20th century Boston surgeon Ernest Codman, who tracked the treatment outcome of all of his patients on “End Result Cards” for at least a year with the goal of identifying errors to improve the care of his future patients. He established the first M&M conference at Harvard and was one of the founders of the American College of Surgeons and the forerunner of the Joint Commission. His idea that surgeon and hospital outcomes should be made public so that patients could make an informed choice about where and from whom to seek care was, however, vigorously resisted by Harvard and Dr. Codman lost his privileges there.

I would offer that the M&M conference and the PSIs are apples and oranges: both good, but different. Each serves a different purpose. But too much integration of the PSI into the M&M format could end up creating a formulaic adverse events conference that answers to bureaucratic needs of the hospital, but loses some of its value as a forum for learning.

It is worth reflecting on how and why the traditional M&M has such value to surgeons.

To begin with, the quality of the leadership matters. A good leader knows how to avoid blaming, shaming, or embarrassing the presenter, who likely feels bad enough about the complication without being tortured about it. The goal is that all salient factors that contributed to the complication are elicited and that everyone present comes away from the conference armed with alternative ways to prevent a repeat of the same complication.

As a resident I learned more at the Saturday morning M&M than I did at any other conference. I was there every Saturday morning almost without fail for 15 years as a medical student, resident, and faculty member. There I learned not only how to avoid errors and benefit from the accumulated wisdom of many gray hairs in the audience, but also how to present an embarrassing complication both honestly and even with some self-deprecating humor.

Chief residents such as Don Trunkey, Brent Eastman, and Theodore Schrock were gifted in being accountable for mistakes while simultaneously deflecting ire with some well-chosen props. I remember one vivid example: Ted Schrock stepping up to the podium to present a “case gone bad” while holding a garbage-can lid in front of his chest like a shield, ready to defend himself. I don’t remember the case, but the picture is still etched in my mind 45 years later.

Our chairman, Dr. J. Englebert Dunphy, was a master at zeroing in on the critical errors in decision-making or operative conduct that had led to a poor outcome. When the presenter was honest and well-meaning but lacking in sophisticated insight, Dr. Dunphy would calmly ask probing questions that guided the resident to understand why a complication had occurred and how it might have been avoided. If the complication was exceptionally egregious, or the resident was not forthright or was evasive in his “mea culpa,” Dr. Dunphy would turn to one of his staunch faculty allies in the front row and inquire, “Brodie, what do you think about that?” to which Brodie Stephens would typically reply, “Bert, I thought we were here to CURE disease, not CAUSE it!” (To add some colorful football lore to the story, Howard Brodie Stephens was the All-American end who caught a 53-yard pass from “Brick” Muller in the 1921 Rose Bowl victory of Cal Berkeley over Ohio State, the Pacific Coast Conference’s last win against a Big Ten team until 1953.)

Certain resident shortcomings were sure to raise Dr. Dunphy’s ire. These included failing to take responsibility for your mistake and attempting to blame the error on someone else or on another discipline or not adequately supervising an intern or junior resident if you were the chief resident. The latter crime was the subject of one of the most clever and resourceful chief resident M&M presentations of all time, that of past ACS President Brent Eastman as his final presentation from his vascular surgery rotation, the last of his chief year. This one took some moxie, considerable preparation, and the involvement of colleagues near and far. Brent enlisted his good friend and later distinguished cardiac surgeon Dr. Larry Cohn, then junior faculty at Harvard, to find a list of Dr. Dunphy’s complications while he was a resident in Boston in the 1930s. Although records were no longer available, Dr. Cohn mentioned the issue to Dr. Hartwell Harrison, who had been chief resident at the Peter Bent Brigham Hospital when Dr. Dunphy was a junior resident. Dr. Harrison remembered a case that Dr. Dunphy had performed in the outpatient clinic without supervision in which he encountered uncontrolled bleeding.

Armed with the perfect case to present, Brent coached Dr. Edwin (Jack) Wylie to be his “plant” in the audience. At M&M, Brent sheepishly admitted that the case he had to present was that of an unsupervised junior resident who incurred uncontrolled bleeding in the outpatient setting. On cue, Dr. Wylie asked, “Who the hell WAS that resident?” Dr. Eastman then shuffled through his papers to find the correct sheet and announced, “Dr. John E. Dunphy, Peter Bent Brigham Hospital, 1937.” The room exploded in uproarious laughter, joined heartily by Dr. Dunphy.

That was then, and this is now. I can’t envision such a spectacle ever occurring these days. The M&M conference of 2018 has become far more standardized and endowed with greater scientific rigor. Its evolution has likely made M&M more precise and valuable as an educational tool for surgeons to learn from the mistakes of others, but of course, it has lost an element of surprise and hilarity that kept all of us sleep-deprived residents awake and alert. The lessons learned from the traditional M&M lasted this surgeon’s lifetime, and we should consider preserving some of the give-and-take, admission of failure, and reflection that made the M&M so unforgettable.
 

Dr. Deveney is professor of surgery and vice chair of education in the department of surgery at Oregon Health & Science University, Portland. She is the coeditor of ACS Surgery News.

Surgeons have a time-honored institution of reflection, learning, and responsibility in the Morbidity & Mortality conference. The M&M is unique in the medical profession and we should look critically at efforts by hospitals and bureaucracies to change its character and its purpose.

A story in this issue (“Little overlap between surgical M&M and AHRQ” on adverse events, p. xx) covers a published study (Anderson J et al. J Am Coll Surg. 2018 Jul 5. doi: 10.1016/j.jamcollsurg.2018.06.008) of the ways in which surgeon-reported M&M cases do (but mostly, do not) overlap with those captured in the ubiquitous Patient Safety Indicators (PSIs).

I am reminded once again of the long road we have traveled from the M&M conference of my student and resident days in the 1970s to today’s version of this event.

At our institution, the M&M has evolved over the years to serve not only an educational venue from which all in attendance learn from the misadventures of others and (hopefully) avoid similar errors in the future, but also as a component of the institution’s overall patient safety and quality improvement program. The authors point out the inherent difference between the clinician-generated M&M cases, which may possess selection bias in the cases they identify as complications, and the strictly defined PSIs that are captured from an administrative database and often include cases overlooked by the clinicians as not relevant to the surgical M&M process.

Both kinds of data are valuable, but for surgeons, the M&M is the one venue where they can focus in the company of their colleagues on those instances where the best intentions go off the rails: erroneous decisions, faulty assessments, and unanticipated complications.

The surgical M&M conference traces its origins to the admirable practice of early 20th century Boston surgeon Ernest Codman, who tracked the treatment outcome of all of his patients on “End Result Cards” for at least a year with the goal of identifying errors to improve the care of his future patients. He established the first M&M conference at Harvard and was one of the founders of the American College of Surgeons and the forerunner of the Joint Commission. His idea that surgeon and hospital outcomes should be made public so that patients could make an informed choice about where and from whom to seek care was, however, vigorously resisted by Harvard and Dr. Codman lost his privileges there.

I would offer that the M&M conference and the PSIs are apples and oranges: both good, but different. Each serves a different purpose. But too much integration of the PSI into the M&M format could end up creating a formulaic adverse events conference that answers to bureaucratic needs of the hospital, but loses some of its value as a forum for learning.

It is worth reflecting on how and why the traditional M&M has such value to surgeons.

To begin with, the quality of the leadership matters. A good leader knows how to avoid blaming, shaming, or embarrassing the presenter, who likely feels bad enough about the complication without being tortured about it. The goal is that all salient factors that contributed to the complication are elicited and that everyone present comes away from the conference armed with alternative ways to prevent a repeat of the same complication.

As a resident I learned more at the Saturday morning M&M than I did at any other conference. I was there every Saturday morning almost without fail for 15 years as a medical student, resident, and faculty member. There I learned not only how to avoid errors and benefit from the accumulated wisdom of many gray hairs in the audience, but also how to present an embarrassing complication both honestly and even with some self-deprecating humor.

Chief residents such as Don Trunkey, Brent Eastman, and Theodore Schrock were gifted in being accountable for mistakes while simultaneously deflecting ire with some well-chosen props. I remember one vivid example: Ted Schrock stepping up to the podium to present a “case gone bad” while holding a garbage-can lid in front of his chest like a shield, ready to defend himself. I don’t remember the case, but the picture is still etched in my mind 45 years later.

Our chairman, Dr. J. Englebert Dunphy, was a master at zeroing in on the critical errors in decision-making or operative conduct that had led to a poor outcome. When the presenter was honest and well-meaning but lacking in sophisticated insight, Dr. Dunphy would calmly ask probing questions that guided the resident to understand why a complication had occurred and how it might have been avoided. If the complication was exceptionally egregious, or the resident was not forthright or was evasive in his “mea culpa,” Dr. Dunphy would turn to one of his staunch faculty allies in the front row and inquire, “Brodie, what do you think about that?” to which Brodie Stephens would typically reply, “Bert, I thought we were here to CURE disease, not CAUSE it!” (To add some colorful football lore to the story, Howard Brodie Stephens was the All-American end who caught a 53-yard pass from “Brick” Muller in the 1921 Rose Bowl victory of Cal Berkeley over Ohio State, the Pacific Coast Conference’s last win against a Big Ten team until 1953.)

Certain resident shortcomings were sure to raise Dr. Dunphy’s ire. These included failing to take responsibility for your mistake and attempting to blame the error on someone else or on another discipline or not adequately supervising an intern or junior resident if you were the chief resident. The latter crime was the subject of one of the most clever and resourceful chief resident M&M presentations of all time, that of past ACS President Brent Eastman as his final presentation from his vascular surgery rotation, the last of his chief year. This one took some moxie, considerable preparation, and the involvement of colleagues near and far. Brent enlisted his good friend and later distinguished cardiac surgeon Dr. Larry Cohn, then junior faculty at Harvard, to find a list of Dr. Dunphy’s complications while he was a resident in Boston in the 1930s. Although records were no longer available, Dr. Cohn mentioned the issue to Dr. Hartwell Harrison, who had been chief resident at the Peter Bent Brigham Hospital when Dr. Dunphy was a junior resident. Dr. Harrison remembered a case that Dr. Dunphy had performed in the outpatient clinic without supervision in which he encountered uncontrolled bleeding.

Armed with the perfect case to present, Brent coached Dr. Edwin (Jack) Wylie to be his “plant” in the audience. At M&M, Brent sheepishly admitted that the case he had to present was that of an unsupervised junior resident who incurred uncontrolled bleeding in the outpatient setting. On cue, Dr. Wylie asked, “Who the hell WAS that resident?” Dr. Eastman then shuffled through his papers to find the correct sheet and announced, “Dr. John E. Dunphy, Peter Bent Brigham Hospital, 1937.” The room exploded in uproarious laughter, joined heartily by Dr. Dunphy.

That was then, and this is now. I can’t envision such a spectacle ever occurring these days. The M&M conference of 2018 has become far more standardized and endowed with greater scientific rigor. Its evolution has likely made M&M more precise and valuable as an educational tool for surgeons to learn from the mistakes of others, but of course, it has lost an element of surprise and hilarity that kept all of us sleep-deprived residents awake and alert. The lessons learned from the traditional M&M lasted this surgeon’s lifetime, and we should consider preserving some of the give-and-take, admission of failure, and reflection that made the M&M so unforgettable.
 

Dr. Deveney is professor of surgery and vice chair of education in the department of surgery at Oregon Health & Science University, Portland. She is the coeditor of ACS Surgery News.

What is the largest endocrine organ in the human body?

Here is a clue: It is also the largest immune organ in humans!

Still scratching your head? Here is another clue: This organ also contains a “second brain,” which is connected to big brain inside the head by the vagus nerve.

Okay, enough guessing: It’s the 30-foot long gastrointestinal (GI) tract, which is generally associated only with eating and digestion. But it is far more than a digestive tract. It is home to about 100 trillion diverse bacteria, including 1,000 known species, which together are known as “microbiota.” Its combined DNA is called the “microbiome” and is 10,000% larger than the human genome. Those trillions of bacteria in our guts are a symbiotic (commensal) organ that is vital for the normal functions of the human body.¹

While this vast array of microorganisms is vital to sustaining a healthy human existence, it can also be involved in multiple psychiatric disorders, including depression, psychosis, anxiety, autism, and attention-deficit/hyperactivity disorder (ADHD). Humans acquire their unique sets of microbiota as they pass through the mother’s vagina at birth and while breastfeeding, as well as from exposure to various environmental sources in the first few months of life.²

The microbiota in the GI tract are an intimate neighbor of the “enteric brain,” comprised of 100 million neurons plus glia-like support cell structures. This “second brain” produces over 30 neuro­transmitters, several of which (dopamine, serotonin, γ-aminobutyric acid [GABA], acetylcholine) have been implicated in major psychiatric disorders.³

The brain and gut have a dynamic bidirectional communication system, mediated by neural, hormonal, and immunological crosstalk and influences. The GI tract secretes dozens of peptides and other signaling molecules that influence the brain. The microbiota also interact with and are regulated by gut hormones such as oxytocin, ghrelin, neuropeptide Y, cholecystokinin, corticotrophin-releasing factor, and pancreatic polypeptide.⁴ The microbiota modulate brain development, functions, and behavior, and maintain the intestinal barrier, which, if disrupted, would result in the gut becoming “leaky” and triggering low-grade inflammation such as that associated with depression.⁵

Continue to: But don't overlook the importance of...

But don’t overlook the importance of diet. It is a major factor in shaping the composition of the microbiota. What we eat can have a preventative or reparative effect on neuroimmune or neuroinflammatory disease. An emerging body of evidence suggests that the diet and its effects on the gut microbiota can modify a person’s genes by epi­genetic mechanisms (altering DNA methylation and histone effects). Probiotics can exert epigenetic effects by influencing cytokines, by producing short-chain fatty acids (SCFAs), by vitamin synthesis, and by producing several well-known neurotransmitters.⁶

The bidirectional trafficking across the microbiome-gut-brain axis includes reciprocal effects. The brain influences the microbiome composition by regulating satiety, the hypothalamic-pituitary axis, and with neuropeptides.⁷ In return, the microbiome conveys information to the brain about the intestinal status via infectious agents, intestinal neuro­transmitters and modulators, cytokines, sensory vagal fibers, and various metabolites. Failure of these normal interactions can lead to a variety of pathological processes, including inflammatory, autoimmune, degenerative, metabolic, cognitive, mood, and behavioral adverse effects. Therapeutic interventions for these adverse consequences can be implemented through microbiome manipulations (such as fecal transplants), nutritional strategies, and reinforcement of the enteric and brain barriers.

Alterations in the microbiota, such as by the intake of antibiotics or by intestinal inflammation, can lead to psychiatric disorders.⁸ The following findings link gut microbiome disruptions with several psychiatric disorders:

Schizophrenia prodrome. Fecal bacteria show an increase in SCFAs, which can activate microglia (the initial step in triggering psychosis).⁹ These bacteria have been shown to lead to an increase in choline levels in the anterior cingulate, a known biomarker for membrane dysfunction, which is one of the biological models of schizophrenia.

Schizophrenia—first-episode. A recent study reported abnormalities in the gut microbiota of patients with first-episode psychosis, with a lower number of certain fecal bacteria (including bifidobacterium, E. coli, and lactobacillus) and high levels of Clostridium coccoides. After 6 months of risperidone treatment, the above changes were reversed.¹⁰

Continue to: Another study of fecal microbiota...

Another study of fecal microbiota in a first-episode psychosis cohort found significant differences in several bacterial strains compared with a healthy control group, and those with the strongest difference had more severe psychotic symptoms and poorer response after 12 months of antipsychotic treatment.¹¹

Autism has been linked to increased microbiota diversity, and an excess of bacteroides has been associated with a higher diversity of autism. Fecal samples from autistic children were reported to have an increase in SCFAs. Interestingly, a certain strain of lactobacillus can modulate oxytocin or reverse some autistic symptoms.

Depression has been associated with increased diversity of microbiota alpha. Patients with depression have been reported to have low numbers of bifidobacterium and lactobacillus. Certain strains have been reported to reduce depression and anxiety behaviors in animal studies. The microbiota-friendly Mediterranean diet, but not the Western diet, appears to mitigate the risk of depression. Certain probiotics have been reported to increase resilience to stress.^12,13

ADHD. Some studies suggest that ADHD may be linked to factors that can alter gut microbiota, including birthing mode, type of infant feeding, maternal health, and early stressors. In addition, dietary influences on gut microbiota can modify ADHD symptoms.¹⁴

Alzheimer’s disease. Metabolic dysregulation, such as obesity and diabetes, can inflame the gut microbiota, and are known risk factors for Alzheimer’s disease.¹⁵

Continue to: Irritable bowel sydrome...

Irritable bowel syndrome (IBS). Fecal microbiota transplantation has been shown to improve IBS by increasing the diversity of gut microbiota.¹⁶ It also improves patients’ mood, not just their IBS symptoms.

Alcohol use. Both alcohol consumption and alcohol withdrawal have been shown to cause immune dysregulation in the brain leading to neuroinflammation. This is attributed to the alteration in the composition of the microbiome (dysbiosis), which has a negative effect on the microbe-host homeostasis.¹⁷

The discovery of microbiome-gut-brain interactions and their bidirectional immune, endocrine, and neurotransmitter effects has been a momentous paradigm shift in health, neuroscience, and psychiatry.¹⁸ It has opened wide vistas of research for potential innovations in the prevention and treatment of various psychiatric disorders. Radical medical interventions that were previously inconceivable, such as fecal transplantation,¹⁹ are an example of the bold insights this new field of microbiome-gut-brain interaction is bringing to the landscape of medicine, including psychiatry. It has also highlighted the previously underappreciated importance of nutrition in health and disease.²⁰

What is the largest endocrine organ in the human body?

Here is a clue: It is also the largest immune organ in humans!

Still scratching your head? Here is another clue: This organ also contains a “second brain,” which is connected to big brain inside the head by the vagus nerve.

Okay, enough guessing: It’s the 30-foot long gastrointestinal (GI) tract, which is generally associated only with eating and digestion. But it is far more than a digestive tract. It is home to about 100 trillion diverse bacteria, including 1,000 known species, which together are known as “microbiota.” Its combined DNA is called the “microbiome” and is 10,000% larger than the human genome. Those trillions of bacteria in our guts are a symbiotic (commensal) organ that is vital for the normal functions of the human body.¹

While this vast array of microorganisms is vital to sustaining a healthy human existence, it can also be involved in multiple psychiatric disorders, including depression, psychosis, anxiety, autism, and attention-deficit/hyperactivity disorder (ADHD). Humans acquire their unique sets of microbiota as they pass through the mother’s vagina at birth and while breastfeeding, as well as from exposure to various environmental sources in the first few months of life.²

The microbiota in the GI tract are an intimate neighbor of the “enteric brain,” comprised of 100 million neurons plus glia-like support cell structures. This “second brain” produces over 30 neuro­transmitters, several of which (dopamine, serotonin, γ-aminobutyric acid [GABA], acetylcholine) have been implicated in major psychiatric disorders.³

The brain and gut have a dynamic bidirectional communication system, mediated by neural, hormonal, and immunological crosstalk and influences. The GI tract secretes dozens of peptides and other signaling molecules that influence the brain. The microbiota also interact with and are regulated by gut hormones such as oxytocin, ghrelin, neuropeptide Y, cholecystokinin, corticotrophin-releasing factor, and pancreatic polypeptide.⁴ The microbiota modulate brain development, functions, and behavior, and maintain the intestinal barrier, which, if disrupted, would result in the gut becoming “leaky” and triggering low-grade inflammation such as that associated with depression.⁵

Continue to: But don't overlook the importance of...

But don’t overlook the importance of diet. It is a major factor in shaping the composition of the microbiota. What we eat can have a preventative or reparative effect on neuroimmune or neuroinflammatory disease. An emerging body of evidence suggests that the diet and its effects on the gut microbiota can modify a person’s genes by epi­genetic mechanisms (altering DNA methylation and histone effects). Probiotics can exert epigenetic effects by influencing cytokines, by producing short-chain fatty acids (SCFAs), by vitamin synthesis, and by producing several well-known neurotransmitters.⁶

The bidirectional trafficking across the microbiome-gut-brain axis includes reciprocal effects. The brain influences the microbiome composition by regulating satiety, the hypothalamic-pituitary axis, and with neuropeptides.⁷ In return, the microbiome conveys information to the brain about the intestinal status via infectious agents, intestinal neuro­transmitters and modulators, cytokines, sensory vagal fibers, and various metabolites. Failure of these normal interactions can lead to a variety of pathological processes, including inflammatory, autoimmune, degenerative, metabolic, cognitive, mood, and behavioral adverse effects. Therapeutic interventions for these adverse consequences can be implemented through microbiome manipulations (such as fecal transplants), nutritional strategies, and reinforcement of the enteric and brain barriers.

Alterations in the microbiota, such as by the intake of antibiotics or by intestinal inflammation, can lead to psychiatric disorders.⁸ The following findings link gut microbiome disruptions with several psychiatric disorders:

Schizophrenia prodrome. Fecal bacteria show an increase in SCFAs, which can activate microglia (the initial step in triggering psychosis).⁹ These bacteria have been shown to lead to an increase in choline levels in the anterior cingulate, a known biomarker for membrane dysfunction, which is one of the biological models of schizophrenia.

Schizophrenia—first-episode. A recent study reported abnormalities in the gut microbiota of patients with first-episode psychosis, with a lower number of certain fecal bacteria (including bifidobacterium, E. coli, and lactobacillus) and high levels of Clostridium coccoides. After 6 months of risperidone treatment, the above changes were reversed.¹⁰

Continue to: Another study of fecal microbiota...

Another study of fecal microbiota in a first-episode psychosis cohort found significant differences in several bacterial strains compared with a healthy control group, and those with the strongest difference had more severe psychotic symptoms and poorer response after 12 months of antipsychotic treatment.¹¹

Autism has been linked to increased microbiota diversity, and an excess of bacteroides has been associated with a higher diversity of autism. Fecal samples from autistic children were reported to have an increase in SCFAs. Interestingly, a certain strain of lactobacillus can modulate oxytocin or reverse some autistic symptoms.

Depression has been associated with increased diversity of microbiota alpha. Patients with depression have been reported to have low numbers of bifidobacterium and lactobacillus. Certain strains have been reported to reduce depression and anxiety behaviors in animal studies. The microbiota-friendly Mediterranean diet, but not the Western diet, appears to mitigate the risk of depression. Certain probiotics have been reported to increase resilience to stress.^12,13

ADHD. Some studies suggest that ADHD may be linked to factors that can alter gut microbiota, including birthing mode, type of infant feeding, maternal health, and early stressors. In addition, dietary influences on gut microbiota can modify ADHD symptoms.¹⁴

Alzheimer’s disease. Metabolic dysregulation, such as obesity and diabetes, can inflame the gut microbiota, and are known risk factors for Alzheimer’s disease.¹⁵

Continue to: Irritable bowel sydrome...

Irritable bowel syndrome (IBS). Fecal microbiota transplantation has been shown to improve IBS by increasing the diversity of gut microbiota.¹⁶ It also improves patients’ mood, not just their IBS symptoms.

Alcohol use. Both alcohol consumption and alcohol withdrawal have been shown to cause immune dysregulation in the brain leading to neuroinflammation. This is attributed to the alteration in the composition of the microbiome (dysbiosis), which has a negative effect on the microbe-host homeostasis.¹⁷

The discovery of microbiome-gut-brain interactions and their bidirectional immune, endocrine, and neurotransmitter effects has been a momentous paradigm shift in health, neuroscience, and psychiatry.¹⁸ It has opened wide vistas of research for potential innovations in the prevention and treatment of various psychiatric disorders. Radical medical interventions that were previously inconceivable, such as fecal transplantation,¹⁹ are an example of the bold insights this new field of microbiome-gut-brain interaction is bringing to the landscape of medicine, including psychiatry. It has also highlighted the previously underappreciated importance of nutrition in health and disease.²⁰

What is the largest endocrine organ in the human body?

Here is a clue: It is also the largest immune organ in humans!

Still scratching your head? Here is another clue: This organ also contains a “second brain,” which is connected to big brain inside the head by the vagus nerve.

Okay, enough guessing: It’s the 30-foot long gastrointestinal (GI) tract, which is generally associated only with eating and digestion. But it is far more than a digestive tract. It is home to about 100 trillion diverse bacteria, including 1,000 known species, which together are known as “microbiota.” Its combined DNA is called the “microbiome” and is 10,000% larger than the human genome. Those trillions of bacteria in our guts are a symbiotic (commensal) organ that is vital for the normal functions of the human body.¹

While this vast array of microorganisms is vital to sustaining a healthy human existence, it can also be involved in multiple psychiatric disorders, including depression, psychosis, anxiety, autism, and attention-deficit/hyperactivity disorder (ADHD). Humans acquire their unique sets of microbiota as they pass through the mother’s vagina at birth and while breastfeeding, as well as from exposure to various environmental sources in the first few months of life.²

The microbiota in the GI tract are an intimate neighbor of the “enteric brain,” comprised of 100 million neurons plus glia-like support cell structures. This “second brain” produces over 30 neuro­transmitters, several of which (dopamine, serotonin, γ-aminobutyric acid [GABA], acetylcholine) have been implicated in major psychiatric disorders.³

The brain and gut have a dynamic bidirectional communication system, mediated by neural, hormonal, and immunological crosstalk and influences. The GI tract secretes dozens of peptides and other signaling molecules that influence the brain. The microbiota also interact with and are regulated by gut hormones such as oxytocin, ghrelin, neuropeptide Y, cholecystokinin, corticotrophin-releasing factor, and pancreatic polypeptide.⁴ The microbiota modulate brain development, functions, and behavior, and maintain the intestinal barrier, which, if disrupted, would result in the gut becoming “leaky” and triggering low-grade inflammation such as that associated with depression.⁵

Continue to: But don't overlook the importance of...

But don’t overlook the importance of diet. It is a major factor in shaping the composition of the microbiota. What we eat can have a preventative or reparative effect on neuroimmune or neuroinflammatory disease. An emerging body of evidence suggests that the diet and its effects on the gut microbiota can modify a person’s genes by epi­genetic mechanisms (altering DNA methylation and histone effects). Probiotics can exert epigenetic effects by influencing cytokines, by producing short-chain fatty acids (SCFAs), by vitamin synthesis, and by producing several well-known neurotransmitters.⁶

The bidirectional trafficking across the microbiome-gut-brain axis includes reciprocal effects. The brain influences the microbiome composition by regulating satiety, the hypothalamic-pituitary axis, and with neuropeptides.⁷ In return, the microbiome conveys information to the brain about the intestinal status via infectious agents, intestinal neuro­transmitters and modulators, cytokines, sensory vagal fibers, and various metabolites. Failure of these normal interactions can lead to a variety of pathological processes, including inflammatory, autoimmune, degenerative, metabolic, cognitive, mood, and behavioral adverse effects. Therapeutic interventions for these adverse consequences can be implemented through microbiome manipulations (such as fecal transplants), nutritional strategies, and reinforcement of the enteric and brain barriers.

Alterations in the microbiota, such as by the intake of antibiotics or by intestinal inflammation, can lead to psychiatric disorders.⁸ The following findings link gut microbiome disruptions with several psychiatric disorders:

Schizophrenia prodrome. Fecal bacteria show an increase in SCFAs, which can activate microglia (the initial step in triggering psychosis).⁹ These bacteria have been shown to lead to an increase in choline levels in the anterior cingulate, a known biomarker for membrane dysfunction, which is one of the biological models of schizophrenia.

Schizophrenia—first-episode. A recent study reported abnormalities in the gut microbiota of patients with first-episode psychosis, with a lower number of certain fecal bacteria (including bifidobacterium, E. coli, and lactobacillus) and high levels of Clostridium coccoides. After 6 months of risperidone treatment, the above changes were reversed.¹⁰

Continue to: Another study of fecal microbiota...

Another study of fecal microbiota in a first-episode psychosis cohort found significant differences in several bacterial strains compared with a healthy control group, and those with the strongest difference had more severe psychotic symptoms and poorer response after 12 months of antipsychotic treatment.¹¹

Autism has been linked to increased microbiota diversity, and an excess of bacteroides has been associated with a higher diversity of autism. Fecal samples from autistic children were reported to have an increase in SCFAs. Interestingly, a certain strain of lactobacillus can modulate oxytocin or reverse some autistic symptoms.

Depression has been associated with increased diversity of microbiota alpha. Patients with depression have been reported to have low numbers of bifidobacterium and lactobacillus. Certain strains have been reported to reduce depression and anxiety behaviors in animal studies. The microbiota-friendly Mediterranean diet, but not the Western diet, appears to mitigate the risk of depression. Certain probiotics have been reported to increase resilience to stress.^12,13

ADHD. Some studies suggest that ADHD may be linked to factors that can alter gut microbiota, including birthing mode, type of infant feeding, maternal health, and early stressors. In addition, dietary influences on gut microbiota can modify ADHD symptoms.¹⁴

Alzheimer’s disease. Metabolic dysregulation, such as obesity and diabetes, can inflame the gut microbiota, and are known risk factors for Alzheimer’s disease.¹⁵

Continue to: Irritable bowel sydrome...

Irritable bowel syndrome (IBS). Fecal microbiota transplantation has been shown to improve IBS by increasing the diversity of gut microbiota.¹⁶ It also improves patients’ mood, not just their IBS symptoms.

Alcohol use. Both alcohol consumption and alcohol withdrawal have been shown to cause immune dysregulation in the brain leading to neuroinflammation. This is attributed to the alteration in the composition of the microbiome (dysbiosis), which has a negative effect on the microbe-host homeostasis.¹⁷

The discovery of microbiome-gut-brain interactions and their bidirectional immune, endocrine, and neurotransmitter effects has been a momentous paradigm shift in health, neuroscience, and psychiatry.¹⁸ It has opened wide vistas of research for potential innovations in the prevention and treatment of various psychiatric disorders. Radical medical interventions that were previously inconceivable, such as fecal transplantation,¹⁹ are an example of the bold insights this new field of microbiome-gut-brain interaction is bringing to the landscape of medicine, including psychiatry. It has also highlighted the previously underappreciated importance of nutrition in health and disease.²⁰

Some drugs exhibit a dose-toxicity relationship that is sufficiently predictable to permit drug-level monitoring to limit renal or other toxicity. Others cause ocular or marrow toxicity that can be limited by weight-based dosing and careful monitoring. With azathioprine, some toxicity can be predicted by assessing the activity of the enzyme thiopurine methyltransferase, which metabolizes the drug. Other approaches to using pharmacogenomics have included HLA-B locus haplotyping to detect increased risk of immune-mediated toxicities of drugs such as carbamazepine and allopurinol. Both of these drugs exhibit serious systemic toxicities that are incompletely understood, but these are nascent and significant steps toward providing personalized (precision) medical care.

Adverse effects of some drugs may result from their intracellular effects, which are only partially predictable by drug levels or dosing. Colchicine, hydroxychloroquine, and amiodarone all affect intracellular vacuolar transport and lysosomal processing. Yet, although the footprints of drug effect can be seen in many histopathology samples, only some patients—but maybe more than currently recognized—suffer cardiac and skeletal muscle vacuolar myopathy, axonal neuropathies, or pulmonary or retinal cell toxicity from these drugs. But distinguishing the histopathologic footprints of drug exposure and the biologic effect from true drug toxicity with organ damage is not always straightforward.

Rare adverse effects may only become apparent with frequent use of a drug in the general community. These often remain mechanistically unexplained: Why can minoxidil cause pericardial effusions or a nonsteroidal anti-inflammatory drug cause aseptic meningitis? Some effects may be due to altering of the unique balance of biochemical pathways in a given patient, leading to unexpected drug metabolism with generation of toxic metabolites.

More interesting to me are effects that are seemingly off-target biologic outcomes caused by disrupting normal physiologic homeostasis and stimulating counterregulatory pathways in such a way that unexpected biologic effects occur. Angioedema and cough in some patients who have taken angiotensin-converting enzyme inhibitors are examples, but why the disturbed control mechanisms lead to these effects in only occasional patients is still incompletely elucidated.

Two additional classes of drugs with unique systemic adverse effects are discussed in this issue of the Journal. The “flulike” syndrome after bisphosphonate treatment, presumably resulting from selective cytokine release by macrophages that have ingested certain bisphosphonates, is a not uncommon and significant annoyance to many patients, and in my experience it is a reason patients discontinue the treatment. Lim and Bolster describe the reaction and their approach to its management, and comment on the fairly obscure pathway that may explain its occurrence. Again, it is not clear to me why only relatively few patients experience the reaction. Is there a genetic predisposition? Or is it influenced by the patient’s baseline “inflammatory tone,” as influenced by the state of his or her microbiome or other still uncharacterized factors? And why does this reaction often diminish with repeated dosing of the drug?

Most striking is the description and discussion by Khan et al of the management of autoimmune colitis after administration of immune checkpoint inhibitor anticancer therapies. These drugs represent important advances in the therapy of various cancers. They are novel in that they are not specific to tumor type, although certain drugs within this new class of immunotherapy seem to exhibit more dramatic and enduring responses against one type of cancer than against another. These therapies are not directly tumor-reactive, but act by down-regulating the normal “brakes” or checkpoints of the immune system that normally play a role in reigning in the immune-inflammatory system response to infection once the offending infective agent is neutralized. These checkpoints have also been thought to limit the development of autoimmunity. Many cancers seem to capitalize on the activation of these brakes to evade tumor immunity. That these checkpoint therapies are so effective in some patients with heretofore unresponsive cancers is obviously a major advance. But equally striking is the scientific proof of the immunologic concept that by inhibiting these normal brakes on inflammation there is loss of normal regulation of the immune response and autoimmunity ensues unchecked. Khan et al discuss the colitis that can occur with these therapies, but a host of fascinating and potentially life-threatening organ-specific complications can be invoked by the checkpoint inhibitors, including hypophysitis, myositis, nephritis, and pneumonitis. What determines which patient will suffer these immune complications, which organs will be affected in a given patient, and the relationships between preexisting autoimmune disease, antitumor response, and these autoimmune complications are still being unraveled.

If you have not yet encountered patients with these complications in your practice, it is quite likely you will. The topic is worth reading about now (see the review by June et al¹), and we will provide additional reviews in the future.

Some drugs exhibit a dose-toxicity relationship that is sufficiently predictable to permit drug-level monitoring to limit renal or other toxicity. Others cause ocular or marrow toxicity that can be limited by weight-based dosing and careful monitoring. With azathioprine, some toxicity can be predicted by assessing the activity of the enzyme thiopurine methyltransferase, which metabolizes the drug. Other approaches to using pharmacogenomics have included HLA-B locus haplotyping to detect increased risk of immune-mediated toxicities of drugs such as carbamazepine and allopurinol. Both of these drugs exhibit serious systemic toxicities that are incompletely understood, but these are nascent and significant steps toward providing personalized (precision) medical care.

Adverse effects of some drugs may result from their intracellular effects, which are only partially predictable by drug levels or dosing. Colchicine, hydroxychloroquine, and amiodarone all affect intracellular vacuolar transport and lysosomal processing. Yet, although the footprints of drug effect can be seen in many histopathology samples, only some patients—but maybe more than currently recognized—suffer cardiac and skeletal muscle vacuolar myopathy, axonal neuropathies, or pulmonary or retinal cell toxicity from these drugs. But distinguishing the histopathologic footprints of drug exposure and the biologic effect from true drug toxicity with organ damage is not always straightforward.

Rare adverse effects may only become apparent with frequent use of a drug in the general community. These often remain mechanistically unexplained: Why can minoxidil cause pericardial effusions or a nonsteroidal anti-inflammatory drug cause aseptic meningitis? Some effects may be due to altering of the unique balance of biochemical pathways in a given patient, leading to unexpected drug metabolism with generation of toxic metabolites.

More interesting to me are effects that are seemingly off-target biologic outcomes caused by disrupting normal physiologic homeostasis and stimulating counterregulatory pathways in such a way that unexpected biologic effects occur. Angioedema and cough in some patients who have taken angiotensin-converting enzyme inhibitors are examples, but why the disturbed control mechanisms lead to these effects in only occasional patients is still incompletely elucidated.

Two additional classes of drugs with unique systemic adverse effects are discussed in this issue of the Journal. The “flulike” syndrome after bisphosphonate treatment, presumably resulting from selective cytokine release by macrophages that have ingested certain bisphosphonates, is a not uncommon and significant annoyance to many patients, and in my experience it is a reason patients discontinue the treatment. Lim and Bolster describe the reaction and their approach to its management, and comment on the fairly obscure pathway that may explain its occurrence. Again, it is not clear to me why only relatively few patients experience the reaction. Is there a genetic predisposition? Or is it influenced by the patient’s baseline “inflammatory tone,” as influenced by the state of his or her microbiome or other still uncharacterized factors? And why does this reaction often diminish with repeated dosing of the drug?

Most striking is the description and discussion by Khan et al of the management of autoimmune colitis after administration of immune checkpoint inhibitor anticancer therapies. These drugs represent important advances in the therapy of various cancers. They are novel in that they are not specific to tumor type, although certain drugs within this new class of immunotherapy seem to exhibit more dramatic and enduring responses against one type of cancer than against another. These therapies are not directly tumor-reactive, but act by down-regulating the normal “brakes” or checkpoints of the immune system that normally play a role in reigning in the immune-inflammatory system response to infection once the offending infective agent is neutralized. These checkpoints have also been thought to limit the development of autoimmunity. Many cancers seem to capitalize on the activation of these brakes to evade tumor immunity. That these checkpoint therapies are so effective in some patients with heretofore unresponsive cancers is obviously a major advance. But equally striking is the scientific proof of the immunologic concept that by inhibiting these normal brakes on inflammation there is loss of normal regulation of the immune response and autoimmunity ensues unchecked. Khan et al discuss the colitis that can occur with these therapies, but a host of fascinating and potentially life-threatening organ-specific complications can be invoked by the checkpoint inhibitors, including hypophysitis, myositis, nephritis, and pneumonitis. What determines which patient will suffer these immune complications, which organs will be affected in a given patient, and the relationships between preexisting autoimmune disease, antitumor response, and these autoimmune complications are still being unraveled.

If you have not yet encountered patients with these complications in your practice, it is quite likely you will. The topic is worth reading about now (see the review by June et al¹), and we will provide additional reviews in the future.

Some drugs exhibit a dose-toxicity relationship that is sufficiently predictable to permit drug-level monitoring to limit renal or other toxicity. Others cause ocular or marrow toxicity that can be limited by weight-based dosing and careful monitoring. With azathioprine, some toxicity can be predicted by assessing the activity of the enzyme thiopurine methyltransferase, which metabolizes the drug. Other approaches to using pharmacogenomics have included HLA-B locus haplotyping to detect increased risk of immune-mediated toxicities of drugs such as carbamazepine and allopurinol. Both of these drugs exhibit serious systemic toxicities that are incompletely understood, but these are nascent and significant steps toward providing personalized (precision) medical care.

Adverse effects of some drugs may result from their intracellular effects, which are only partially predictable by drug levels or dosing. Colchicine, hydroxychloroquine, and amiodarone all affect intracellular vacuolar transport and lysosomal processing. Yet, although the footprints of drug effect can be seen in many histopathology samples, only some patients—but maybe more than currently recognized—suffer cardiac and skeletal muscle vacuolar myopathy, axonal neuropathies, or pulmonary or retinal cell toxicity from these drugs. But distinguishing the histopathologic footprints of drug exposure and the biologic effect from true drug toxicity with organ damage is not always straightforward.

Rare adverse effects may only become apparent with frequent use of a drug in the general community. These often remain mechanistically unexplained: Why can minoxidil cause pericardial effusions or a nonsteroidal anti-inflammatory drug cause aseptic meningitis? Some effects may be due to altering of the unique balance of biochemical pathways in a given patient, leading to unexpected drug metabolism with generation of toxic metabolites.

More interesting to me are effects that are seemingly off-target biologic outcomes caused by disrupting normal physiologic homeostasis and stimulating counterregulatory pathways in such a way that unexpected biologic effects occur. Angioedema and cough in some patients who have taken angiotensin-converting enzyme inhibitors are examples, but why the disturbed control mechanisms lead to these effects in only occasional patients is still incompletely elucidated.

Two additional classes of drugs with unique systemic adverse effects are discussed in this issue of the Journal. The “flulike” syndrome after bisphosphonate treatment, presumably resulting from selective cytokine release by macrophages that have ingested certain bisphosphonates, is a not uncommon and significant annoyance to many patients, and in my experience it is a reason patients discontinue the treatment. Lim and Bolster describe the reaction and their approach to its management, and comment on the fairly obscure pathway that may explain its occurrence. Again, it is not clear to me why only relatively few patients experience the reaction. Is there a genetic predisposition? Or is it influenced by the patient’s baseline “inflammatory tone,” as influenced by the state of his or her microbiome or other still uncharacterized factors? And why does this reaction often diminish with repeated dosing of the drug?

Most striking is the description and discussion by Khan et al of the management of autoimmune colitis after administration of immune checkpoint inhibitor anticancer therapies. These drugs represent important advances in the therapy of various cancers. They are novel in that they are not specific to tumor type, although certain drugs within this new class of immunotherapy seem to exhibit more dramatic and enduring responses against one type of cancer than against another. These therapies are not directly tumor-reactive, but act by down-regulating the normal “brakes” or checkpoints of the immune system that normally play a role in reigning in the immune-inflammatory system response to infection once the offending infective agent is neutralized. These checkpoints have also been thought to limit the development of autoimmunity. Many cancers seem to capitalize on the activation of these brakes to evade tumor immunity. That these checkpoint therapies are so effective in some patients with heretofore unresponsive cancers is obviously a major advance. But equally striking is the scientific proof of the immunologic concept that by inhibiting these normal brakes on inflammation there is loss of normal regulation of the immune response and autoimmunity ensues unchecked. Khan et al discuss the colitis that can occur with these therapies, but a host of fascinating and potentially life-threatening organ-specific complications can be invoked by the checkpoint inhibitors, including hypophysitis, myositis, nephritis, and pneumonitis. What determines which patient will suffer these immune complications, which organs will be affected in a given patient, and the relationships between preexisting autoimmune disease, antitumor response, and these autoimmune complications are still being unraveled.

If you have not yet encountered patients with these complications in your practice, it is quite likely you will. The topic is worth reading about now (see the review by June et al¹), and we will provide additional reviews in the future.

As summer winds down and we begin to gear up to return to school or work, I was thinking about new and returning hem-onc residents, fellows, and young attendings and a question I routinely get from them: what should I do next in my career? I always answer by holding up 3 fingers and telling them that they can practice 1, at a university hospital; 2, at a university teaching affiliate; or 3, at a community hospital or practice with a little or no university affiliation. These days, trainees in hematology-oncology are often advised to be highly specialty-specific when they plan their long-term careers and to focus on a particular cancer or hematologic disorder. That is fine if you want to remain in an academic or university-based practice, but not if community practice is your preference. So, what are the differences among these 3 options?

Option 1, to remain in a university setting where you can be highly focused and specialized in a single narrowly defined area, could be satisfying, but keep in mind that the institution expects results! You will be carefully monitored for research output and teaching and administration commitments, and your interaction with patients could add up to less than 50% of your time. Publication and grant renewal will also play a role and therefore take up your time.

If you are considering option 2 – to work at a university teaching affiliate hospital – you need to bear in mind that you likely will see a patient population with a much broader range of diagnoses than would be the case with the first option. Patient care for option 2 will take up more than 50% of your time, so it might be a little more challenging to stay current, but perhaps more refreshing if you enjoy contact with patients. Teaching, research, and administration will surely be available, and publication and grant renewal will play as big or small a role as you want.

Option 3 would be to join a community hospital or practice where the primary focus is on patient care and the diagnoses will span the hematology and oncology spectrum. This type of practice can be very demanding of one’s time, but as rewarding as the other options, especially if you value contact with patients. With this option, one is more likely to practice as a generalist, perhaps with an emphasis in one of the hem-onc specialties, but able to treat a cluster of different types of cancer as well.

I always advise trainees to be sure they ask physicians practicing in each of these options to give examples of what their best and worst days are like so that they can get some idea of what the daily humdrum and challenges would encompass. What did I choose? I have always gone with option 2 and have been very happy in that setting.

In this issue…

More biosimilars head our way. Turning to the current issue of the journal, on page e181, Dr Jane de Lartigue discusses 2 new biosimilars recently approved by the United States Food and Drug Administration (FDA) – epoetin alfa-epbx (Retacrit; Hospira, a Pfizer company) for chemotherapy-induced anemia (CIA), and pegfilgrastim-jmdb (Fulphila; Mylan and Biocon) for prevention of febrile neutropenia. As Dr de Lartigue notes, biosimilars are copies of FDA-approved biologic drugs that cannot be identical to the reference drug but demonstrate a high similarity to it. In this case, the reference drug for epoetin alfa-epbx is epoetin alfa (Epogen/Procrit, Amgen) and for pegfilgrastim-jmdb, it is pegfilgrastim (Neulasta, Amgen). As the reference drugs’ patents expire, biosimilars are being developed to increase competition in the marketplace in an effort to reduce costs and improve patient access to these therapies. Indeed, the FDA is working to streamline the biosimilar approval process to facilitate that access.

Reading this article got me thinking about something I often have to consider in the course of my work: transfusion versus erythropoiesis-stimulating agents (ESAs)? Recombinant erythropoietin drugs such as the biosimilar, epoetin alfa-epbx, and its reference drug are grouped together as ESAs, and have been used to treat CIA since the late 1980s. However, there were a few trials that used higher-dose ESA or set high hemoglobin targets, and their findings suggested that ESAs may shorten survival in patients with cancer or increase tumor growth, or both. The use of ESAs took a nosedive after the 2007 decision by the FDA’s Oncologic Drugs Advisory Committee to rein in their use for a hard start of ESA treatment at less than 10 g/dL hemoglobin, and not higher. Subsequent trials addressed the concerns about survival and tumor growth. A meta-analysis of 60 randomized, placebo-controlled trials of ESAs in CIA found that there was no difference in overall survival between the study and control groups.¹ Likewise, findings from an FDA-mandated trial with epoetin alfa (Procrit) in patients with metastatic breast cancer have reported that there was no significant difference in overall survival between the study and control groups.² The results of a second FDA-mandated trial with darbepoetin alfa (Aranesp, Amgen) in patients with metastatic lung cancer are expected to be released soon. The FDA lifted the ESA Risk Evaluation and Mitigation Strategy based on those findings. However, many practitioners, both young and old, continue to shy away from using ESAs because of the FDA black box warning that remains in place despite the latest data.³The use of transfusion ticked up reciprocally with the decline in ESA use, but perhaps we should re-evaluate the use of these agents in our practice, especially now that the less costly, equally safe and effective biosimilars are becoming available and we have the new survival data. Transfusions are time consuming and have side effects, including allergic reaction and infection risk, whereas ESAs are easily administered by injection, which patients might find preferable.

Malignancies in patients with HIV-AIDS. On page e188, Koppaka and colleagues report on a study in India of the patterns of malignancies in patients with HIV-AIDS. I began my career just as the first reports of what became known as HIV-AIDS emerged, and we were all mystified by what was killing these patients and the curious hematologic and oncologic problems they developed. Back then, the patients were profoundly immunosuppressed, and the immunosuppression cancers of non-Hodgkin lymphoma, usually higher grade, and Kaposi sarcoma were most prevalent and today are collectively labeled AIDS-defining malignancies (ADMs).

Fast forward to present day, and we have extremely effective antiretroviral therapies that have resulted in a significant reduction in mortality among HIV-infected individuals who are now living long enough to get what we call non–AIDS-defining malignancies (NADMs) such as anal or cervical cancers, hepatoma (hepatocellular carcinoma), Hodgkin lymphoma, and lung cancer. Of note is that these NADMs are all highly viral associated, with anal and cervical cancers linked to infection with the human papillomavirus; hepatoma linked to the hepatitis B/C viruses; Hodgkin lymphoma to the Epstein-Barr virus; and lung cancer, possibly also HPV. Fortunately, these days we can use standard-dose chemoradiation therapy for all HIV-related cancers because the patients’ immune systems are much better reconstituted and the modern-day antiretroviral therapies have much less drug–drug interaction thanks to the advent of the integrase inhibitors. The researchers give an excellent breakdown of the occurrence of these malignancies, as well as an analysis of the correlation between CD4 counts and the different malignancies.

Immunotherapy-related side effects in the ED. What happens when our patients who are on immunotherapy end up in the emergency department (ED) with therapy-related symptoms? And what can the treating oncologist do to help the ED physician achieve the best possible outcome for the patient? I spoke to Dr Maura Sammon, an ED physician, about some of the more common of these side effects – lung, gastrointestinal, rash, and endocrine-related problems – and she describes in detail how physicians in the ED would triage and treat the patient. Dr Sammon also emphasizes the importance of communication: first, between the treating oncologist and patient, about the differences between chemotherapy and immunotherapy; and second, between the ED physician and the treating oncologist as soon as possible after the patient has presented to ensure a good outcome. The interview is part of The JCSO Interview series. It is jam-packed with useful, how-to information, and you can read a transcript of it on page e216 of this issue, or you can listen to it online.⁴

We round off the issue with a selection of Case Reports (pp. e200-e209), an original report on the characteristics of urgent palliative cancer care consultations encountered by radiation oncologists (p. e193), and a New Therapies feature, also by Dr de Lartigue, focusing on the rarity and complexities of sarcomas (p. e210).

Those are my dog-day-of-summer thoughts as we head toward another Labor Day and a new academic year. Since we are all online now, we encourage you to listen to my bimonthly podcast of each issue on our website at www.jcso-online.com, and of course, follow us on Twitter (@jcs_onc) and Instagram (@jcsoncology) and like us on Facebook.

As summer winds down and we begin to gear up to return to school or work, I was thinking about new and returning hem-onc residents, fellows, and young attendings and a question I routinely get from them: what should I do next in my career? I always answer by holding up 3 fingers and telling them that they can practice 1, at a university hospital; 2, at a university teaching affiliate; or 3, at a community hospital or practice with a little or no university affiliation. These days, trainees in hematology-oncology are often advised to be highly specialty-specific when they plan their long-term careers and to focus on a particular cancer or hematologic disorder. That is fine if you want to remain in an academic or university-based practice, but not if community practice is your preference. So, what are the differences among these 3 options?

Option 1, to remain in a university setting where you can be highly focused and specialized in a single narrowly defined area, could be satisfying, but keep in mind that the institution expects results! You will be carefully monitored for research output and teaching and administration commitments, and your interaction with patients could add up to less than 50% of your time. Publication and grant renewal will also play a role and therefore take up your time.

If you are considering option 2 – to work at a university teaching affiliate hospital – you need to bear in mind that you likely will see a patient population with a much broader range of diagnoses than would be the case with the first option. Patient care for option 2 will take up more than 50% of your time, so it might be a little more challenging to stay current, but perhaps more refreshing if you enjoy contact with patients. Teaching, research, and administration will surely be available, and publication and grant renewal will play as big or small a role as you want.

Option 3 would be to join a community hospital or practice where the primary focus is on patient care and the diagnoses will span the hematology and oncology spectrum. This type of practice can be very demanding of one’s time, but as rewarding as the other options, especially if you value contact with patients. With this option, one is more likely to practice as a generalist, perhaps with an emphasis in one of the hem-onc specialties, but able to treat a cluster of different types of cancer as well.

I always advise trainees to be sure they ask physicians practicing in each of these options to give examples of what their best and worst days are like so that they can get some idea of what the daily humdrum and challenges would encompass. What did I choose? I have always gone with option 2 and have been very happy in that setting.

In this issue…

More biosimilars head our way. Turning to the current issue of the journal, on page e181, Dr Jane de Lartigue discusses 2 new biosimilars recently approved by the United States Food and Drug Administration (FDA) – epoetin alfa-epbx (Retacrit; Hospira, a Pfizer company) for chemotherapy-induced anemia (CIA), and pegfilgrastim-jmdb (Fulphila; Mylan and Biocon) for prevention of febrile neutropenia. As Dr de Lartigue notes, biosimilars are copies of FDA-approved biologic drugs that cannot be identical to the reference drug but demonstrate a high similarity to it. In this case, the reference drug for epoetin alfa-epbx is epoetin alfa (Epogen/Procrit, Amgen) and for pegfilgrastim-jmdb, it is pegfilgrastim (Neulasta, Amgen). As the reference drugs’ patents expire, biosimilars are being developed to increase competition in the marketplace in an effort to reduce costs and improve patient access to these therapies. Indeed, the FDA is working to streamline the biosimilar approval process to facilitate that access.

Reading this article got me thinking about something I often have to consider in the course of my work: transfusion versus erythropoiesis-stimulating agents (ESAs)? Recombinant erythropoietin drugs such as the biosimilar, epoetin alfa-epbx, and its reference drug are grouped together as ESAs, and have been used to treat CIA since the late 1980s. However, there were a few trials that used higher-dose ESA or set high hemoglobin targets, and their findings suggested that ESAs may shorten survival in patients with cancer or increase tumor growth, or both. The use of ESAs took a nosedive after the 2007 decision by the FDA’s Oncologic Drugs Advisory Committee to rein in their use for a hard start of ESA treatment at less than 10 g/dL hemoglobin, and not higher. Subsequent trials addressed the concerns about survival and tumor growth. A meta-analysis of 60 randomized, placebo-controlled trials of ESAs in CIA found that there was no difference in overall survival between the study and control groups.¹ Likewise, findings from an FDA-mandated trial with epoetin alfa (Procrit) in patients with metastatic breast cancer have reported that there was no significant difference in overall survival between the study and control groups.² The results of a second FDA-mandated trial with darbepoetin alfa (Aranesp, Amgen) in patients with metastatic lung cancer are expected to be released soon. The FDA lifted the ESA Risk Evaluation and Mitigation Strategy based on those findings. However, many practitioners, both young and old, continue to shy away from using ESAs because of the FDA black box warning that remains in place despite the latest data.³The use of transfusion ticked up reciprocally with the decline in ESA use, but perhaps we should re-evaluate the use of these agents in our practice, especially now that the less costly, equally safe and effective biosimilars are becoming available and we have the new survival data. Transfusions are time consuming and have side effects, including allergic reaction and infection risk, whereas ESAs are easily administered by injection, which patients might find preferable.

Malignancies in patients with HIV-AIDS. On page e188, Koppaka and colleagues report on a study in India of the patterns of malignancies in patients with HIV-AIDS. I began my career just as the first reports of what became known as HIV-AIDS emerged, and we were all mystified by what was killing these patients and the curious hematologic and oncologic problems they developed. Back then, the patients were profoundly immunosuppressed, and the immunosuppression cancers of non-Hodgkin lymphoma, usually higher grade, and Kaposi sarcoma were most prevalent and today are collectively labeled AIDS-defining malignancies (ADMs).

Fast forward to present day, and we have extremely effective antiretroviral therapies that have resulted in a significant reduction in mortality among HIV-infected individuals who are now living long enough to get what we call non–AIDS-defining malignancies (NADMs) such as anal or cervical cancers, hepatoma (hepatocellular carcinoma), Hodgkin lymphoma, and lung cancer. Of note is that these NADMs are all highly viral associated, with anal and cervical cancers linked to infection with the human papillomavirus; hepatoma linked to the hepatitis B/C viruses; Hodgkin lymphoma to the Epstein-Barr virus; and lung cancer, possibly also HPV. Fortunately, these days we can use standard-dose chemoradiation therapy for all HIV-related cancers because the patients’ immune systems are much better reconstituted and the modern-day antiretroviral therapies have much less drug–drug interaction thanks to the advent of the integrase inhibitors. The researchers give an excellent breakdown of the occurrence of these malignancies, as well as an analysis of the correlation between CD4 counts and the different malignancies.

Immunotherapy-related side effects in the ED. What happens when our patients who are on immunotherapy end up in the emergency department (ED) with therapy-related symptoms? And what can the treating oncologist do to help the ED physician achieve the best possible outcome for the patient? I spoke to Dr Maura Sammon, an ED physician, about some of the more common of these side effects – lung, gastrointestinal, rash, and endocrine-related problems – and she describes in detail how physicians in the ED would triage and treat the patient. Dr Sammon also emphasizes the importance of communication: first, between the treating oncologist and patient, about the differences between chemotherapy and immunotherapy; and second, between the ED physician and the treating oncologist as soon as possible after the patient has presented to ensure a good outcome. The interview is part of The JCSO Interview series. It is jam-packed with useful, how-to information, and you can read a transcript of it on page e216 of this issue, or you can listen to it online.⁴

We round off the issue with a selection of Case Reports (pp. e200-e209), an original report on the characteristics of urgent palliative cancer care consultations encountered by radiation oncologists (p. e193), and a New Therapies feature, also by Dr de Lartigue, focusing on the rarity and complexities of sarcomas (p. e210).

Those are my dog-day-of-summer thoughts as we head toward another Labor Day and a new academic year. Since we are all online now, we encourage you to listen to my bimonthly podcast of each issue on our website at www.jcso-online.com, and of course, follow us on Twitter (@jcs_onc) and Instagram (@jcsoncology) and like us on Facebook.

As summer winds down and we begin to gear up to return to school or work, I was thinking about new and returning hem-onc residents, fellows, and young attendings and a question I routinely get from them: what should I do next in my career? I always answer by holding up 3 fingers and telling them that they can practice 1, at a university hospital; 2, at a university teaching affiliate; or 3, at a community hospital or practice with a little or no university affiliation. These days, trainees in hematology-oncology are often advised to be highly specialty-specific when they plan their long-term careers and to focus on a particular cancer or hematologic disorder. That is fine if you want to remain in an academic or university-based practice, but not if community practice is your preference. So, what are the differences among these 3 options?

Option 1, to remain in a university setting where you can be highly focused and specialized in a single narrowly defined area, could be satisfying, but keep in mind that the institution expects results! You will be carefully monitored for research output and teaching and administration commitments, and your interaction with patients could add up to less than 50% of your time. Publication and grant renewal will also play a role and therefore take up your time.

If you are considering option 2 – to work at a university teaching affiliate hospital – you need to bear in mind that you likely will see a patient population with a much broader range of diagnoses than would be the case with the first option. Patient care for option 2 will take up more than 50% of your time, so it might be a little more challenging to stay current, but perhaps more refreshing if you enjoy contact with patients. Teaching, research, and administration will surely be available, and publication and grant renewal will play as big or small a role as you want.

Option 3 would be to join a community hospital or practice where the primary focus is on patient care and the diagnoses will span the hematology and oncology spectrum. This type of practice can be very demanding of one’s time, but as rewarding as the other options, especially if you value contact with patients. With this option, one is more likely to practice as a generalist, perhaps with an emphasis in one of the hem-onc specialties, but able to treat a cluster of different types of cancer as well.

I always advise trainees to be sure they ask physicians practicing in each of these options to give examples of what their best and worst days are like so that they can get some idea of what the daily humdrum and challenges would encompass. What did I choose? I have always gone with option 2 and have been very happy in that setting.

In this issue…

More biosimilars head our way. Turning to the current issue of the journal, on page e181, Dr Jane de Lartigue discusses 2 new biosimilars recently approved by the United States Food and Drug Administration (FDA) – epoetin alfa-epbx (Retacrit; Hospira, a Pfizer company) for chemotherapy-induced anemia (CIA), and pegfilgrastim-jmdb (Fulphila; Mylan and Biocon) for prevention of febrile neutropenia. As Dr de Lartigue notes, biosimilars are copies of FDA-approved biologic drugs that cannot be identical to the reference drug but demonstrate a high similarity to it. In this case, the reference drug for epoetin alfa-epbx is epoetin alfa (Epogen/Procrit, Amgen) and for pegfilgrastim-jmdb, it is pegfilgrastim (Neulasta, Amgen). As the reference drugs’ patents expire, biosimilars are being developed to increase competition in the marketplace in an effort to reduce costs and improve patient access to these therapies. Indeed, the FDA is working to streamline the biosimilar approval process to facilitate that access.

Reading this article got me thinking about something I often have to consider in the course of my work: transfusion versus erythropoiesis-stimulating agents (ESAs)? Recombinant erythropoietin drugs such as the biosimilar, epoetin alfa-epbx, and its reference drug are grouped together as ESAs, and have been used to treat CIA since the late 1980s. However, there were a few trials that used higher-dose ESA or set high hemoglobin targets, and their findings suggested that ESAs may shorten survival in patients with cancer or increase tumor growth, or both. The use of ESAs took a nosedive after the 2007 decision by the FDA’s Oncologic Drugs Advisory Committee to rein in their use for a hard start of ESA treatment at less than 10 g/dL hemoglobin, and not higher. Subsequent trials addressed the concerns about survival and tumor growth. A meta-analysis of 60 randomized, placebo-controlled trials of ESAs in CIA found that there was no difference in overall survival between the study and control groups.¹ Likewise, findings from an FDA-mandated trial with epoetin alfa (Procrit) in patients with metastatic breast cancer have reported that there was no significant difference in overall survival between the study and control groups.² The results of a second FDA-mandated trial with darbepoetin alfa (Aranesp, Amgen) in patients with metastatic lung cancer are expected to be released soon. The FDA lifted the ESA Risk Evaluation and Mitigation Strategy based on those findings. However, many practitioners, both young and old, continue to shy away from using ESAs because of the FDA black box warning that remains in place despite the latest data.³The use of transfusion ticked up reciprocally with the decline in ESA use, but perhaps we should re-evaluate the use of these agents in our practice, especially now that the less costly, equally safe and effective biosimilars are becoming available and we have the new survival data. Transfusions are time consuming and have side effects, including allergic reaction and infection risk, whereas ESAs are easily administered by injection, which patients might find preferable.

Malignancies in patients with HIV-AIDS. On page e188, Koppaka and colleagues report on a study in India of the patterns of malignancies in patients with HIV-AIDS. I began my career just as the first reports of what became known as HIV-AIDS emerged, and we were all mystified by what was killing these patients and the curious hematologic and oncologic problems they developed. Back then, the patients were profoundly immunosuppressed, and the immunosuppression cancers of non-Hodgkin lymphoma, usually higher grade, and Kaposi sarcoma were most prevalent and today are collectively labeled AIDS-defining malignancies (ADMs).

Fast forward to present day, and we have extremely effective antiretroviral therapies that have resulted in a significant reduction in mortality among HIV-infected individuals who are now living long enough to get what we call non–AIDS-defining malignancies (NADMs) such as anal or cervical cancers, hepatoma (hepatocellular carcinoma), Hodgkin lymphoma, and lung cancer. Of note is that these NADMs are all highly viral associated, with anal and cervical cancers linked to infection with the human papillomavirus; hepatoma linked to the hepatitis B/C viruses; Hodgkin lymphoma to the Epstein-Barr virus; and lung cancer, possibly also HPV. Fortunately, these days we can use standard-dose chemoradiation therapy for all HIV-related cancers because the patients’ immune systems are much better reconstituted and the modern-day antiretroviral therapies have much less drug–drug interaction thanks to the advent of the integrase inhibitors. The researchers give an excellent breakdown of the occurrence of these malignancies, as well as an analysis of the correlation between CD4 counts and the different malignancies.

Immunotherapy-related side effects in the ED. What happens when our patients who are on immunotherapy end up in the emergency department (ED) with therapy-related symptoms? And what can the treating oncologist do to help the ED physician achieve the best possible outcome for the patient? I spoke to Dr Maura Sammon, an ED physician, about some of the more common of these side effects – lung, gastrointestinal, rash, and endocrine-related problems – and she describes in detail how physicians in the ED would triage and treat the patient. Dr Sammon also emphasizes the importance of communication: first, between the treating oncologist and patient, about the differences between chemotherapy and immunotherapy; and second, between the ED physician and the treating oncologist as soon as possible after the patient has presented to ensure a good outcome. The interview is part of The JCSO Interview series. It is jam-packed with useful, how-to information, and you can read a transcript of it on page e216 of this issue, or you can listen to it online.⁴

We round off the issue with a selection of Case Reports (pp. e200-e209), an original report on the characteristics of urgent palliative cancer care consultations encountered by radiation oncologists (p. e193), and a New Therapies feature, also by Dr de Lartigue, focusing on the rarity and complexities of sarcomas (p. e210).

Those are my dog-day-of-summer thoughts as we head toward another Labor Day and a new academic year. Since we are all online now, we encourage you to listen to my bimonthly podcast of each issue on our website at www.jcso-online.com, and of course, follow us on Twitter (@jcs_onc) and Instagram (@jcsoncology) and like us on Facebook.

When I grow up, I want to be a fireman. Not long ago, I had occasion to revisit why firefighters are such heroes to young and old. In the process, I learned quite a bit about how fires are managed and realized that a really good surgeon has much in common with a fire Incident Commander.

Gilitukha/Thinkstock

In late June 2018, a man started a fire in Southern Colorado. That small campfire became the Spring Fire, the third-largest forest fire in Colorado history, which is saying a lot. By the time the fire was mostly contained 2 weeks later, 175 square miles of land had been burned and 1,800 firefighters were involved in the disaster. More than 150 homes were destroyed. Not one person died in or as a result of this fire. Only the most grudging of critics would deny that, while the fire itself was a disaster, the response and outcome constituted a good definition of success.

This story was more than just 30 seconds on the nightly news to me because I was one of the people whose property and 32 years of precious family memories were in danger. I clung to any news of the fire. My own daughter had to evacuate our place there when smoke and flame were visible just a few miles away. I was helpless to do anything but hoped that somehow this conflagration could be stopped.

Within 48 hours, Rocky Mountain Black Team – headed by a man named Shane Greer – arrived in the area. Mr. Greer is the Incident Commander of the Black Team. Over the next 10 days he was the personification of the response to the Spring Fire. He was the main person carrying the overall responsibility for controlling the fire.

The fire is over now, but I reflect frequently on the parallels between surgery and firefighting. I identified with Mr. Greer as probably many did. He didn’t actually stop the fire, but he led the people who did. I was intrigued by this role and I did a little research in fire Incident Commanders. Here’s a list of their numerous roles and responsibilities that I gleaned from an article on the website Firehouse by editor Dennis Rubin from several years ago:
 

• The Incident Commander (IC) must be a qualified, single, central, and well-supported individual.
• The IC’s main concern is safety of lives and must be conversant in fire-safety procedures.
• The IC must have an understanding of his/her personal limitations. An IC must have firsthand experience at firefighting so that the IC is an individual well informed of the difficulties being experienced on the front line of the fire.
• The priorities of the IC are a) life safety; b) incident stabilization; and c) property conservation.
• The IC develops strategies (what to do) and tactics (how to do it) and follows action plans to achieve these goals.
• The IC develops a management structure that uses span of control (one supervisor per five subordinates) with each unit having a single boss.
• A good IC is a good delegator and calls for help early in the incident including placement of resources in staging areas.
• The IC is responsible for all communication among the team and to the media/public.
• The IC coordinates with outside agencies.

Does this sound familiar to you? Substitute surgeon for IC and you have today’s profile of a good surgeon. When executed well, everyone involved in an incident gets to be a hero and feels a part of something bigger than themselves. The IC (surgeon) gets a lot of credit, but that person also makes sure the whole team gets all the credit and thanks they deserve.

What I see happening in some situations is that we in medicine are putting the wrong ICs in charge or abdicating our positions as IC to others because being an IC is a hard, demanding, full-time job. I also see medicine violating the principles in the first bullet point above – a single, central, and well-supported individual. We get the job of IC and then payers, administrators, and outside agencies drop the support part of the ball. We also have a tendency to violate the “qualified” part of the job description. Someone who has put on the gown and gloves and borne the responsibility of operating should be the quarterback and not someone who has only observed that process.

I can’t thank enough the Black Team and all those who fought the Spring Fire. I hope we all aspire to be ICs in our surgical world. There is a great nobility in such professions as firefighting and surgery, where we jump in to help others who can’t help themselves. The Black Team showed that to me and my community in Colorado. It makes one proud of what we human beings can do when we decide to work together.

True leadership and teamwork do not fragment but instead pull resources together. Patients need that. They need to know that a qualified, single, central, and well-supported person is directing their incident. The existence of such a person fulfilling that role is key to keep the trust that the public places in us. May all our “fires” be led by a good surgeon, er, Incident Commander surgeon.

Dr. Hughes is clinical professor in the department of surgery and director of medical education at the Kansas University School of Medicine, Salina Campus, and Co-Editor of ACS Surgery News.

When I grow up, I want to be a fireman. Not long ago, I had occasion to revisit why firefighters are such heroes to young and old. In the process, I learned quite a bit about how fires are managed and realized that a really good surgeon has much in common with a fire Incident Commander.

Gilitukha/Thinkstock

In late June 2018, a man started a fire in Southern Colorado. That small campfire became the Spring Fire, the third-largest forest fire in Colorado history, which is saying a lot. By the time the fire was mostly contained 2 weeks later, 175 square miles of land had been burned and 1,800 firefighters were involved in the disaster. More than 150 homes were destroyed. Not one person died in or as a result of this fire. Only the most grudging of critics would deny that, while the fire itself was a disaster, the response and outcome constituted a good definition of success.

This story was more than just 30 seconds on the nightly news to me because I was one of the people whose property and 32 years of precious family memories were in danger. I clung to any news of the fire. My own daughter had to evacuate our place there when smoke and flame were visible just a few miles away. I was helpless to do anything but hoped that somehow this conflagration could be stopped.

Within 48 hours, Rocky Mountain Black Team – headed by a man named Shane Greer – arrived in the area. Mr. Greer is the Incident Commander of the Black Team. Over the next 10 days he was the personification of the response to the Spring Fire. He was the main person carrying the overall responsibility for controlling the fire.

The fire is over now, but I reflect frequently on the parallels between surgery and firefighting. I identified with Mr. Greer as probably many did. He didn’t actually stop the fire, but he led the people who did. I was intrigued by this role and I did a little research in fire Incident Commanders. Here’s a list of their numerous roles and responsibilities that I gleaned from an article on the website Firehouse by editor Dennis Rubin from several years ago:
 

• The Incident Commander (IC) must be a qualified, single, central, and well-supported individual.
• The IC’s main concern is safety of lives and must be conversant in fire-safety procedures.
• The IC must have an understanding of his/her personal limitations. An IC must have firsthand experience at firefighting so that the IC is an individual well informed of the difficulties being experienced on the front line of the fire.
• The priorities of the IC are a) life safety; b) incident stabilization; and c) property conservation.
• The IC develops strategies (what to do) and tactics (how to do it) and follows action plans to achieve these goals.
• The IC develops a management structure that uses span of control (one supervisor per five subordinates) with each unit having a single boss.
• A good IC is a good delegator and calls for help early in the incident including placement of resources in staging areas.
• The IC is responsible for all communication among the team and to the media/public.
• The IC coordinates with outside agencies.

Does this sound familiar to you? Substitute surgeon for IC and you have today’s profile of a good surgeon. When executed well, everyone involved in an incident gets to be a hero and feels a part of something bigger than themselves. The IC (surgeon) gets a lot of credit, but that person also makes sure the whole team gets all the credit and thanks they deserve.

What I see happening in some situations is that we in medicine are putting the wrong ICs in charge or abdicating our positions as IC to others because being an IC is a hard, demanding, full-time job. I also see medicine violating the principles in the first bullet point above – a single, central, and well-supported individual. We get the job of IC and then payers, administrators, and outside agencies drop the support part of the ball. We also have a tendency to violate the “qualified” part of the job description. Someone who has put on the gown and gloves and borne the responsibility of operating should be the quarterback and not someone who has only observed that process.

I can’t thank enough the Black Team and all those who fought the Spring Fire. I hope we all aspire to be ICs in our surgical world. There is a great nobility in such professions as firefighting and surgery, where we jump in to help others who can’t help themselves. The Black Team showed that to me and my community in Colorado. It makes one proud of what we human beings can do when we decide to work together.

True leadership and teamwork do not fragment but instead pull resources together. Patients need that. They need to know that a qualified, single, central, and well-supported person is directing their incident. The existence of such a person fulfilling that role is key to keep the trust that the public places in us. May all our “fires” be led by a good surgeon, er, Incident Commander surgeon.

Dr. Hughes is clinical professor in the department of surgery and director of medical education at the Kansas University School of Medicine, Salina Campus, and Co-Editor of ACS Surgery News.

When I grow up, I want to be a fireman. Not long ago, I had occasion to revisit why firefighters are such heroes to young and old. In the process, I learned quite a bit about how fires are managed and realized that a really good surgeon has much in common with a fire Incident Commander.

Gilitukha/Thinkstock

In late June 2018, a man started a fire in Southern Colorado. That small campfire became the Spring Fire, the third-largest forest fire in Colorado history, which is saying a lot. By the time the fire was mostly contained 2 weeks later, 175 square miles of land had been burned and 1,800 firefighters were involved in the disaster. More than 150 homes were destroyed. Not one person died in or as a result of this fire. Only the most grudging of critics would deny that, while the fire itself was a disaster, the response and outcome constituted a good definition of success.

This story was more than just 30 seconds on the nightly news to me because I was one of the people whose property and 32 years of precious family memories were in danger. I clung to any news of the fire. My own daughter had to evacuate our place there when smoke and flame were visible just a few miles away. I was helpless to do anything but hoped that somehow this conflagration could be stopped.

Within 48 hours, Rocky Mountain Black Team – headed by a man named Shane Greer – arrived in the area. Mr. Greer is the Incident Commander of the Black Team. Over the next 10 days he was the personification of the response to the Spring Fire. He was the main person carrying the overall responsibility for controlling the fire.

The fire is over now, but I reflect frequently on the parallels between surgery and firefighting. I identified with Mr. Greer as probably many did. He didn’t actually stop the fire, but he led the people who did. I was intrigued by this role and I did a little research in fire Incident Commanders. Here’s a list of their numerous roles and responsibilities that I gleaned from an article on the website Firehouse by editor Dennis Rubin from several years ago:
 

• The Incident Commander (IC) must be a qualified, single, central, and well-supported individual.
• The IC’s main concern is safety of lives and must be conversant in fire-safety procedures.
• The IC must have an understanding of his/her personal limitations. An IC must have firsthand experience at firefighting so that the IC is an individual well informed of the difficulties being experienced on the front line of the fire.
• The priorities of the IC are a) life safety; b) incident stabilization; and c) property conservation.
• The IC develops strategies (what to do) and tactics (how to do it) and follows action plans to achieve these goals.
• The IC develops a management structure that uses span of control (one supervisor per five subordinates) with each unit having a single boss.
• A good IC is a good delegator and calls for help early in the incident including placement of resources in staging areas.
• The IC is responsible for all communication among the team and to the media/public.
• The IC coordinates with outside agencies.

Does this sound familiar to you? Substitute surgeon for IC and you have today’s profile of a good surgeon. When executed well, everyone involved in an incident gets to be a hero and feels a part of something bigger than themselves. The IC (surgeon) gets a lot of credit, but that person also makes sure the whole team gets all the credit and thanks they deserve.

What I see happening in some situations is that we in medicine are putting the wrong ICs in charge or abdicating our positions as IC to others because being an IC is a hard, demanding, full-time job. I also see medicine violating the principles in the first bullet point above – a single, central, and well-supported individual. We get the job of IC and then payers, administrators, and outside agencies drop the support part of the ball. We also have a tendency to violate the “qualified” part of the job description. Someone who has put on the gown and gloves and borne the responsibility of operating should be the quarterback and not someone who has only observed that process.

I can’t thank enough the Black Team and all those who fought the Spring Fire. I hope we all aspire to be ICs in our surgical world. There is a great nobility in such professions as firefighting and surgery, where we jump in to help others who can’t help themselves. The Black Team showed that to me and my community in Colorado. It makes one proud of what we human beings can do when we decide to work together.

True leadership and teamwork do not fragment but instead pull resources together. Patients need that. They need to know that a qualified, single, central, and well-supported person is directing their incident. The existence of such a person fulfilling that role is key to keep the trust that the public places in us. May all our “fires” be led by a good surgeon, er, Incident Commander surgeon.

Dr. Hughes is clinical professor in the department of surgery and director of medical education at the Kansas University School of Medicine, Salina Campus, and Co-Editor of ACS Surgery News.