Bleeding wound

The US Food and Drug Administration (FDA) has approved marketing of an expandable, multi-sponge wound dressing to control bleeding from certain types of wounds inflicted in battle.

The dressing, called XSTAT, is for military use only. It is intended for use on gunshot or shrapnel wounds in areas where a tourniquet cannot be placed, such as the groin or armpit.

The dressing can be used for up to 4 hours, which could allow time for a patient to receive surgical care.

XSTAT consists of 3 syringe-style applicators containing 92 compressed cellulose sponges that have an absorbent coating.

The sponges expand and swell to fill the wound cavity, after approximately 20 seconds upon contact with water from blood or bodily fluid. This creates a temporary physical barrier to blood flow.

The number of sponges needed for effective hemorrhage control will vary depending on the size and depth of the wound. Up to 3 applicators may be used on a patient.

The tablet-shaped sponges are each 9.8 mm in diameter and 4 mm to 5 mm in height. They can absorb 3 mL of blood or body fluid. An applicator filled with 92 sponges, therefore, can absorb about 300 mL of fluid.

The sponges cannot be absorbed by the body, and all sponges must be removed before a wound is closed. For ease of visualization and to confirm removal of every sponge, each sponge contains a marker that is visible via X-ray.

The FDA reviewed XSTAT through its de novo classification process, a regulatory pathway for some novel, low-to-moderate-risk medical devices that are the first of their kind.

Before approving XSTAT, the FDA reviewed data from animal studies demonstrating the product’s ability to stop bleeding and its absorption capacity. The agency also reviewed non-clinical biocompatibility data and results of human factors testing.

XSTAT is manufactured by RevMedX, Inc., in Wilsonville, Oregon. For more information on XSTAT, see the company’s website.

Bleeding wound

The US Food and Drug Administration (FDA) has approved marketing of an expandable, multi-sponge wound dressing to control bleeding from certain types of wounds inflicted in battle.

The dressing, called XSTAT, is for military use only. It is intended for use on gunshot or shrapnel wounds in areas where a tourniquet cannot be placed, such as the groin or armpit.

The dressing can be used for up to 4 hours, which could allow time for a patient to receive surgical care.

XSTAT consists of 3 syringe-style applicators containing 92 compressed cellulose sponges that have an absorbent coating.

The sponges expand and swell to fill the wound cavity, after approximately 20 seconds upon contact with water from blood or bodily fluid. This creates a temporary physical barrier to blood flow.

The number of sponges needed for effective hemorrhage control will vary depending on the size and depth of the wound. Up to 3 applicators may be used on a patient.

The tablet-shaped sponges are each 9.8 mm in diameter and 4 mm to 5 mm in height. They can absorb 3 mL of blood or body fluid. An applicator filled with 92 sponges, therefore, can absorb about 300 mL of fluid.

The sponges cannot be absorbed by the body, and all sponges must be removed before a wound is closed. For ease of visualization and to confirm removal of every sponge, each sponge contains a marker that is visible via X-ray.

The FDA reviewed XSTAT through its de novo classification process, a regulatory pathway for some novel, low-to-moderate-risk medical devices that are the first of their kind.

Before approving XSTAT, the FDA reviewed data from animal studies demonstrating the product’s ability to stop bleeding and its absorption capacity. The agency also reviewed non-clinical biocompatibility data and results of human factors testing.

XSTAT is manufactured by RevMedX, Inc., in Wilsonville, Oregon. For more information on XSTAT, see the company’s website.

Bleeding wound

The US Food and Drug Administration (FDA) has approved marketing of an expandable, multi-sponge wound dressing to control bleeding from certain types of wounds inflicted in battle.

The dressing, called XSTAT, is for military use only. It is intended for use on gunshot or shrapnel wounds in areas where a tourniquet cannot be placed, such as the groin or armpit.

The dressing can be used for up to 4 hours, which could allow time for a patient to receive surgical care.

XSTAT consists of 3 syringe-style applicators containing 92 compressed cellulose sponges that have an absorbent coating.

The sponges expand and swell to fill the wound cavity, after approximately 20 seconds upon contact with water from blood or bodily fluid. This creates a temporary physical barrier to blood flow.

The number of sponges needed for effective hemorrhage control will vary depending on the size and depth of the wound. Up to 3 applicators may be used on a patient.

The tablet-shaped sponges are each 9.8 mm in diameter and 4 mm to 5 mm in height. They can absorb 3 mL of blood or body fluid. An applicator filled with 92 sponges, therefore, can absorb about 300 mL of fluid.

The sponges cannot be absorbed by the body, and all sponges must be removed before a wound is closed. For ease of visualization and to confirm removal of every sponge, each sponge contains a marker that is visible via X-ray.

The FDA reviewed XSTAT through its de novo classification process, a regulatory pathway for some novel, low-to-moderate-risk medical devices that are the first of their kind.

Before approving XSTAT, the FDA reviewed data from animal studies demonstrating the product’s ability to stop bleeding and its absorption capacity. The agency also reviewed non-clinical biocompatibility data and results of human factors testing.

XSTAT is manufactured by RevMedX, Inc., in Wilsonville, Oregon. For more information on XSTAT, see the company’s website.

A sickled red blood cell

and a normal one

Betty Pace

The UK’s National Institute for Health and Care Excellence (NICE) has published a new quality standard to improve care for patients with acute painful episodes resulting from sickle cell disease (SCD).

NICE quality standards include statements that describe high-priority areas for improvement in a defined care or service area.

The current standard builds upon the 2012 NICE clinical guideline for the management of acute painful sickle cell episodes.

The standard states that SCD patients who present at the hospital with a pain episode should have a thorough assessment and receive appropriate pain relief within 30 minutes.

They should then be assessed regularly until satisfactory pain relief has been achieved, with careful monitoring of adverse events in those who are taking strong opioids.

Patients should be assessed for symptoms of acute chest syndrome, such as chest pain, fever, and abnormal respiratory signs.

Healthcare professionals must have access to locally agreed protocols on treatment and management, as well as support from specialist centers.

Healthcare professionals should also provide SCD patients with clear written information to encourage involvement in their continuing care.

“We know that the management of this condition is variable across the country, and there is a need to address patient concerns, such as unacceptable delays in receiving pain relief,” said Gillian Leng, Deputy Chief Executive and Director of Health and Social Care at NICE.

“This new standard will drive up the quality of care people with sickle cell receive, so that they can be confident they will be comfortable during their stay in hospital.”

NICE quality standards are not requirements or targets, but the health and social care system is obliged to consider them in planning and delivering services.

A sickled red blood cell

and a normal one

Betty Pace

The UK’s National Institute for Health and Care Excellence (NICE) has published a new quality standard to improve care for patients with acute painful episodes resulting from sickle cell disease (SCD).

NICE quality standards include statements that describe high-priority areas for improvement in a defined care or service area.

The current standard builds upon the 2012 NICE clinical guideline for the management of acute painful sickle cell episodes.

The standard states that SCD patients who present at the hospital with a pain episode should have a thorough assessment and receive appropriate pain relief within 30 minutes.

They should then be assessed regularly until satisfactory pain relief has been achieved, with careful monitoring of adverse events in those who are taking strong opioids.

Patients should be assessed for symptoms of acute chest syndrome, such as chest pain, fever, and abnormal respiratory signs.

Healthcare professionals must have access to locally agreed protocols on treatment and management, as well as support from specialist centers.

Healthcare professionals should also provide SCD patients with clear written information to encourage involvement in their continuing care.

“We know that the management of this condition is variable across the country, and there is a need to address patient concerns, such as unacceptable delays in receiving pain relief,” said Gillian Leng, Deputy Chief Executive and Director of Health and Social Care at NICE.

“This new standard will drive up the quality of care people with sickle cell receive, so that they can be confident they will be comfortable during their stay in hospital.”

NICE quality standards are not requirements or targets, but the health and social care system is obliged to consider them in planning and delivering services.

A sickled red blood cell

and a normal one

Betty Pace

The UK’s National Institute for Health and Care Excellence (NICE) has published a new quality standard to improve care for patients with acute painful episodes resulting from sickle cell disease (SCD).

NICE quality standards include statements that describe high-priority areas for improvement in a defined care or service area.

The current standard builds upon the 2012 NICE clinical guideline for the management of acute painful sickle cell episodes.

The standard states that SCD patients who present at the hospital with a pain episode should have a thorough assessment and receive appropriate pain relief within 30 minutes.

They should then be assessed regularly until satisfactory pain relief has been achieved, with careful monitoring of adverse events in those who are taking strong opioids.

Patients should be assessed for symptoms of acute chest syndrome, such as chest pain, fever, and abnormal respiratory signs.

Healthcare professionals must have access to locally agreed protocols on treatment and management, as well as support from specialist centers.

Healthcare professionals should also provide SCD patients with clear written information to encourage involvement in their continuing care.

“We know that the management of this condition is variable across the country, and there is a need to address patient concerns, such as unacceptable delays in receiving pain relief,” said Gillian Leng, Deputy Chief Executive and Director of Health and Social Care at NICE.

“This new standard will drive up the quality of care people with sickle cell receive, so that they can be confident they will be comfortable during their stay in hospital.”

NICE quality standards are not requirements or targets, but the health and social care system is obliged to consider them in planning and delivering services.

Doctor consulting

with a cancer patient

NCI/Mathews Media Group

The American Society of Clinical Oncology (ASCO) has issued 3 practice guidelines for preventing and managing symptoms that can affect adult cancer survivors—neuropathy, fatigue, and depression/anxiety.

The guideline on chemotherapy-induced peripheral neuropathy (CIPN) lists a few options for treating the condition but discourages interventions to prevent CIPN, as there is insufficient evidence that these interventions benefit patients.

The guideline on fatigue recommends that healthcare providers start screening cancer patients for the condition at diagnosis and emphasizes the importance of educating patients about fatigue.

The guideline on depression and anxiety recommends periodic evaluations for symptoms of depression and anxiety in all cancer patients. It also suggests that all patients be offered supportive care services.

All 3 of these guidelines are published in the Journal of Clinical Oncology.

Treating and preventing CIPN

ASCO’s guideline on CIPN lists a handful of drugs that may be helpful in diminishing the symptoms of CIPN, but it does not recommend any agents for preventing the condition.

In fact, the guideline provides a list of agents that should not be offered for the prevention of CIPN, including acetyl-L-carnitine, amifostine, amitriptyline, CaMg, diethyldithio-carbamate, glutathione, nimodipine, Org 2766, all-trans retinoic acid, rhuLIF, and vitamin E.

“There is no clear panacea for neuropathy,” said Gary Lyman, MD, MPH, co-chair of the ASCO Survivorship Guidelines Advisory Group.

“Some of the drugs used for prevention or treatment of neuropathy may cause side effects or interfere with other drugs. We want to be clear that if there is no evidence of benefit from those drugs, it’s probably best not to take them.”

As for treatment, the guideline states that data support a “moderate” recommendation for duloxetine.

It also notes that there is no strong evidence of benefit for the use of tricyclic antidepressants, gabapentin, and a topical gel containing baclofen, amitriptyline, and ketamine. However, it may be reasonable to try those agents in select patients.

To develop this guideline, an ASCO panel conducted a systematic review of relevant medical literature. They analyzed data from 48 randomized, clinical trials focused on managing CIPN.

Screening and managing fatigue

ASCO’s guideline on fatigue recommends that all patients be screened for fatigue from the point of diagnosis onward. Healthcare providers should assess fatigue history, disease status, and treatable contributing factors.

All patients should be educated about the differences between normal and cancer-related fatigue, causes of fatigue, and contributing factors.

Healthcare providers should discuss with patients strategies to manage fatigue, including physical activity, psychosocial interventions (such as cognitive and behavioral therapies or psycho-educational therapies), and mind-body interventions (such as yoga or acupuncture).

To develop this guideline, an ASCO panel conducted a systematic review of clinical practice guideline databases and relevant medical literature. The adaptation is based on a Pan-Canadian guideline on fatigue and 2 National Comprehensive Cancer Network guidelines on cancer-related fatigue and survivorship.

Handling anxiety and depression

ASCO’s guideline on anxiety and depression recommends that healthcare providers periodically evaluate all cancer patients for symptoms of depression and anxiety. The assessments should be performed using validated, published measures and procedures.

All patients should have the option of receiving supportive care services, such as education about the normalcy of stress in the context of cancer, signs and symptoms of distress, and stress reduction strategies.

Patients who display moderate or severe symptoms of anxiety and depression should be referred for the appropriate psychological, psychosocial, or psychiatric interventions.

“Doctors sometimes don’t give these symptoms much attention because they think it’s normal that their patients are a little anxious or depressed about their disease,” Dr Lyman said. “But it’s important to keep an eye on the symptoms and step in when they start to interfere with the patients’ quality of life.”

To develop this guideline, an ASCO panel conducted a systematic review of clinical practice guideline databases and relevant medical literature. The adaptation is based on a Pan-Canadian practice guideline on psychological distress in adults with cancer.

Doctor consulting

with a cancer patient

NCI/Mathews Media Group

The American Society of Clinical Oncology (ASCO) has issued 3 practice guidelines for preventing and managing symptoms that can affect adult cancer survivors—neuropathy, fatigue, and depression/anxiety.

The guideline on chemotherapy-induced peripheral neuropathy (CIPN) lists a few options for treating the condition but discourages interventions to prevent CIPN, as there is insufficient evidence that these interventions benefit patients.

The guideline on fatigue recommends that healthcare providers start screening cancer patients for the condition at diagnosis and emphasizes the importance of educating patients about fatigue.

The guideline on depression and anxiety recommends periodic evaluations for symptoms of depression and anxiety in all cancer patients. It also suggests that all patients be offered supportive care services.

All 3 of these guidelines are published in the Journal of Clinical Oncology.

Treating and preventing CIPN

ASCO’s guideline on CIPN lists a handful of drugs that may be helpful in diminishing the symptoms of CIPN, but it does not recommend any agents for preventing the condition.

In fact, the guideline provides a list of agents that should not be offered for the prevention of CIPN, including acetyl-L-carnitine, amifostine, amitriptyline, CaMg, diethyldithio-carbamate, glutathione, nimodipine, Org 2766, all-trans retinoic acid, rhuLIF, and vitamin E.

“There is no clear panacea for neuropathy,” said Gary Lyman, MD, MPH, co-chair of the ASCO Survivorship Guidelines Advisory Group.

“Some of the drugs used for prevention or treatment of neuropathy may cause side effects or interfere with other drugs. We want to be clear that if there is no evidence of benefit from those drugs, it’s probably best not to take them.”

As for treatment, the guideline states that data support a “moderate” recommendation for duloxetine.

It also notes that there is no strong evidence of benefit for the use of tricyclic antidepressants, gabapentin, and a topical gel containing baclofen, amitriptyline, and ketamine. However, it may be reasonable to try those agents in select patients.

To develop this guideline, an ASCO panel conducted a systematic review of relevant medical literature. They analyzed data from 48 randomized, clinical trials focused on managing CIPN.

Screening and managing fatigue

ASCO’s guideline on fatigue recommends that all patients be screened for fatigue from the point of diagnosis onward. Healthcare providers should assess fatigue history, disease status, and treatable contributing factors.

All patients should be educated about the differences between normal and cancer-related fatigue, causes of fatigue, and contributing factors.

Healthcare providers should discuss with patients strategies to manage fatigue, including physical activity, psychosocial interventions (such as cognitive and behavioral therapies or psycho-educational therapies), and mind-body interventions (such as yoga or acupuncture).

To develop this guideline, an ASCO panel conducted a systematic review of clinical practice guideline databases and relevant medical literature. The adaptation is based on a Pan-Canadian guideline on fatigue and 2 National Comprehensive Cancer Network guidelines on cancer-related fatigue and survivorship.

Handling anxiety and depression

ASCO’s guideline on anxiety and depression recommends that healthcare providers periodically evaluate all cancer patients for symptoms of depression and anxiety. The assessments should be performed using validated, published measures and procedures.

All patients should have the option of receiving supportive care services, such as education about the normalcy of stress in the context of cancer, signs and symptoms of distress, and stress reduction strategies.

Patients who display moderate or severe symptoms of anxiety and depression should be referred for the appropriate psychological, psychosocial, or psychiatric interventions.

“Doctors sometimes don’t give these symptoms much attention because they think it’s normal that their patients are a little anxious or depressed about their disease,” Dr Lyman said. “But it’s important to keep an eye on the symptoms and step in when they start to interfere with the patients’ quality of life.”

To develop this guideline, an ASCO panel conducted a systematic review of clinical practice guideline databases and relevant medical literature. The adaptation is based on a Pan-Canadian practice guideline on psychological distress in adults with cancer.

Doctor consulting

with a cancer patient

NCI/Mathews Media Group

The American Society of Clinical Oncology (ASCO) has issued 3 practice guidelines for preventing and managing symptoms that can affect adult cancer survivors—neuropathy, fatigue, and depression/anxiety.

The guideline on chemotherapy-induced peripheral neuropathy (CIPN) lists a few options for treating the condition but discourages interventions to prevent CIPN, as there is insufficient evidence that these interventions benefit patients.

The guideline on fatigue recommends that healthcare providers start screening cancer patients for the condition at diagnosis and emphasizes the importance of educating patients about fatigue.

The guideline on depression and anxiety recommends periodic evaluations for symptoms of depression and anxiety in all cancer patients. It also suggests that all patients be offered supportive care services.

All 3 of these guidelines are published in the Journal of Clinical Oncology.

Treating and preventing CIPN

ASCO’s guideline on CIPN lists a handful of drugs that may be helpful in diminishing the symptoms of CIPN, but it does not recommend any agents for preventing the condition.

In fact, the guideline provides a list of agents that should not be offered for the prevention of CIPN, including acetyl-L-carnitine, amifostine, amitriptyline, CaMg, diethyldithio-carbamate, glutathione, nimodipine, Org 2766, all-trans retinoic acid, rhuLIF, and vitamin E.

“There is no clear panacea for neuropathy,” said Gary Lyman, MD, MPH, co-chair of the ASCO Survivorship Guidelines Advisory Group.

“Some of the drugs used for prevention or treatment of neuropathy may cause side effects or interfere with other drugs. We want to be clear that if there is no evidence of benefit from those drugs, it’s probably best not to take them.”

As for treatment, the guideline states that data support a “moderate” recommendation for duloxetine.

It also notes that there is no strong evidence of benefit for the use of tricyclic antidepressants, gabapentin, and a topical gel containing baclofen, amitriptyline, and ketamine. However, it may be reasonable to try those agents in select patients.

To develop this guideline, an ASCO panel conducted a systematic review of relevant medical literature. They analyzed data from 48 randomized, clinical trials focused on managing CIPN.

Screening and managing fatigue

ASCO’s guideline on fatigue recommends that all patients be screened for fatigue from the point of diagnosis onward. Healthcare providers should assess fatigue history, disease status, and treatable contributing factors.

All patients should be educated about the differences between normal and cancer-related fatigue, causes of fatigue, and contributing factors.

Healthcare providers should discuss with patients strategies to manage fatigue, including physical activity, psychosocial interventions (such as cognitive and behavioral therapies or psycho-educational therapies), and mind-body interventions (such as yoga or acupuncture).

To develop this guideline, an ASCO panel conducted a systematic review of clinical practice guideline databases and relevant medical literature. The adaptation is based on a Pan-Canadian guideline on fatigue and 2 National Comprehensive Cancer Network guidelines on cancer-related fatigue and survivorship.

Handling anxiety and depression

ASCO’s guideline on anxiety and depression recommends that healthcare providers periodically evaluate all cancer patients for symptoms of depression and anxiety. The assessments should be performed using validated, published measures and procedures.

All patients should have the option of receiving supportive care services, such as education about the normalcy of stress in the context of cancer, signs and symptoms of distress, and stress reduction strategies.

Patients who display moderate or severe symptoms of anxiety and depression should be referred for the appropriate psychological, psychosocial, or psychiatric interventions.

“Doctors sometimes don’t give these symptoms much attention because they think it’s normal that their patients are a little anxious or depressed about their disease,” Dr Lyman said. “But it’s important to keep an eye on the symptoms and step in when they start to interfere with the patients’ quality of life.”

To develop this guideline, an ASCO panel conducted a systematic review of clinical practice guideline databases and relevant medical literature. The adaptation is based on a Pan-Canadian practice guideline on psychological distress in adults with cancer.

SAN DIEGO—A dual kinase inhibitor shows potential for treating the heterogeneous acute myeloid leukemia (AML) population, researchers say.

The inhibitor, SEL24-B489, targets both PIM and FLT3 mutants. In experiments, it exhibited more consistent activity across AML cell lines than inhibitors directed only at PIM or FLT3.

SEL24-B489 also demonstrated synergistic activity with cytarabine, both in AML cell lines and mouse models of the disease.

The researchers believe these results suggest SEL24-B489 could potentially treat a range of AML patients and might prove effective regardless of FLT3 status.

“When you have a very heterogeneous population of AML patients, some of them have different FLT mutations, and the problem with FLT inhibitors has been the resistance that occurs in the tyrosine kinase domain,” said Krzysztof D. Brzózka, PhD, of Selvita, the Kraków, Poland-based company developing SEL24-B489.

“We believe that since FLT is upstream, and PIM kinases are downstream of the FLT signaling, we will have higher chances

of overcoming resistance because we are targeting the same pathway at 2 independent nodes.”

Dr Brzózka and his colleagues presented research to support this theory at the AACR Annual Meeting 2014 as abstract 1749.*

The researchers evaluated SEL24-B489 in a range of AML cell lines: MV4-11, MOLM-13, MOLM-16, KG-1, CMK, and HL-60. The drug showed “strong cytotoxicity” across the cell lines, independent of FLT3 status.

The team also compared SEL24-B489 to the PIM inhibitor AZD1208 and the FLT3 inhibitor AC220 in MV4-11 cell lines and MOLM-16 cell lines.

In MV4-11 cells, the IC₅₀ was 0.003 μM for AC220, 0.15 μM for SEL24-B489, and 2.24 μM for AZD1208. In MOLM-16 cells, the IC₅₀ was 0.07 μM for AZD1208, 0.1 μM for SEL24-B489, and >10 μM for AC220.

The researchers then evaluated SEL24-B489 in combination with cytarabine.

“The molecule shows very strong synergistic effects with cytarabine, both in vitro and in vivo,” Dr Brzózka said. “The combination index in vitro is approximately 0.1, 0.2. And in vivo, that translates to [nearly] 100% tumor growth inhibition.”

Tumor growth inhibition (TGI) measured 60% when mice received cytarabine alone at 50 mg/kg. TGI was 77% with SEL24-B489 alone at 25 mg/kg and 82% with SEL24-B489 alone at 50 mg/kg.

But with 25 mg/kg of SEL24-B489 and 50 mg/kg of cytarabine, TGI was 89%. And when both drugs were given at 50 mg/kg, TGI was 99%.

The researchers also assessed SEL24-B489 alone in mouse models of AML. In mice injected with MV4-11 cells, SEL24-B489 at 25 mg/kg BID reduced tumor volume by more than 50%, when compared to untreated control mice. And SEL24-B489 at 75 mg/kg BID reduced tumor volume by more than 80%.

In mice injected with MOLM-16 cells, SEL24-B489 at 25 mg/kg BID reduced tumor volume by more than 80%, when compared to untreated control mice. And SEL24-B489 at 75 mg/kg BID reduced tumor volume by more than 100%.

Finally, the team evaluated the safety of SEL24-B489 via repeated 5-day and 10-day toxicology studies in rats.

And they concluded that doses of 100 mg/kg QD x 5 and 25 mg/kg BID x 10 were safe, based on data concerning body weight gain, as well as results of clinical chemistry, hematology, necropsy, and histological analyses.

“Overall, SEL24-B489 has very good oral bioavailability and initial safety profiling,” Dr Brzózka said. “Both in vitro and in vivo, it shows a pretty promising therapeutic index.”

He and his colleagues are now studying SEL24-B489 in dogs, and Selvita is looking for a partner company to help move the drug to phase 1 trials.

*Information in the abstract differs from that presented at the meeting.

SAN DIEGO—A dual kinase inhibitor shows potential for treating the heterogeneous acute myeloid leukemia (AML) population, researchers say.

The inhibitor, SEL24-B489, targets both PIM and FLT3 mutants. In experiments, it exhibited more consistent activity across AML cell lines than inhibitors directed only at PIM or FLT3.

SEL24-B489 also demonstrated synergistic activity with cytarabine, both in AML cell lines and mouse models of the disease.

The researchers believe these results suggest SEL24-B489 could potentially treat a range of AML patients and might prove effective regardless of FLT3 status.

“When you have a very heterogeneous population of AML patients, some of them have different FLT mutations, and the problem with FLT inhibitors has been the resistance that occurs in the tyrosine kinase domain,” said Krzysztof D. Brzózka, PhD, of Selvita, the Kraków, Poland-based company developing SEL24-B489.

“We believe that since FLT is upstream, and PIM kinases are downstream of the FLT signaling, we will have higher chances

of overcoming resistance because we are targeting the same pathway at 2 independent nodes.”

Dr Brzózka and his colleagues presented research to support this theory at the AACR Annual Meeting 2014 as abstract 1749.*

The researchers evaluated SEL24-B489 in a range of AML cell lines: MV4-11, MOLM-13, MOLM-16, KG-1, CMK, and HL-60. The drug showed “strong cytotoxicity” across the cell lines, independent of FLT3 status.

The team also compared SEL24-B489 to the PIM inhibitor AZD1208 and the FLT3 inhibitor AC220 in MV4-11 cell lines and MOLM-16 cell lines.

In MV4-11 cells, the IC₅₀ was 0.003 μM for AC220, 0.15 μM for SEL24-B489, and 2.24 μM for AZD1208. In MOLM-16 cells, the IC₅₀ was 0.07 μM for AZD1208, 0.1 μM for SEL24-B489, and >10 μM for AC220.

The researchers then evaluated SEL24-B489 in combination with cytarabine.

“The molecule shows very strong synergistic effects with cytarabine, both in vitro and in vivo,” Dr Brzózka said. “The combination index in vitro is approximately 0.1, 0.2. And in vivo, that translates to [nearly] 100% tumor growth inhibition.”

Tumor growth inhibition (TGI) measured 60% when mice received cytarabine alone at 50 mg/kg. TGI was 77% with SEL24-B489 alone at 25 mg/kg and 82% with SEL24-B489 alone at 50 mg/kg.

But with 25 mg/kg of SEL24-B489 and 50 mg/kg of cytarabine, TGI was 89%. And when both drugs were given at 50 mg/kg, TGI was 99%.

The researchers also assessed SEL24-B489 alone in mouse models of AML. In mice injected with MV4-11 cells, SEL24-B489 at 25 mg/kg BID reduced tumor volume by more than 50%, when compared to untreated control mice. And SEL24-B489 at 75 mg/kg BID reduced tumor volume by more than 80%.

In mice injected with MOLM-16 cells, SEL24-B489 at 25 mg/kg BID reduced tumor volume by more than 80%, when compared to untreated control mice. And SEL24-B489 at 75 mg/kg BID reduced tumor volume by more than 100%.

Finally, the team evaluated the safety of SEL24-B489 via repeated 5-day and 10-day toxicology studies in rats.

And they concluded that doses of 100 mg/kg QD x 5 and 25 mg/kg BID x 10 were safe, based on data concerning body weight gain, as well as results of clinical chemistry, hematology, necropsy, and histological analyses.

“Overall, SEL24-B489 has very good oral bioavailability and initial safety profiling,” Dr Brzózka said. “Both in vitro and in vivo, it shows a pretty promising therapeutic index.”

He and his colleagues are now studying SEL24-B489 in dogs, and Selvita is looking for a partner company to help move the drug to phase 1 trials.

*Information in the abstract differs from that presented at the meeting.

SAN DIEGO—A dual kinase inhibitor shows potential for treating the heterogeneous acute myeloid leukemia (AML) population, researchers say.

The inhibitor, SEL24-B489, targets both PIM and FLT3 mutants. In experiments, it exhibited more consistent activity across AML cell lines than inhibitors directed only at PIM or FLT3.

SEL24-B489 also demonstrated synergistic activity with cytarabine, both in AML cell lines and mouse models of the disease.

The researchers believe these results suggest SEL24-B489 could potentially treat a range of AML patients and might prove effective regardless of FLT3 status.

“When you have a very heterogeneous population of AML patients, some of them have different FLT mutations, and the problem with FLT inhibitors has been the resistance that occurs in the tyrosine kinase domain,” said Krzysztof D. Brzózka, PhD, of Selvita, the Kraków, Poland-based company developing SEL24-B489.

“We believe that since FLT is upstream, and PIM kinases are downstream of the FLT signaling, we will have higher chances

of overcoming resistance because we are targeting the same pathway at 2 independent nodes.”

Dr Brzózka and his colleagues presented research to support this theory at the AACR Annual Meeting 2014 as abstract 1749.*

The researchers evaluated SEL24-B489 in a range of AML cell lines: MV4-11, MOLM-13, MOLM-16, KG-1, CMK, and HL-60. The drug showed “strong cytotoxicity” across the cell lines, independent of FLT3 status.

The team also compared SEL24-B489 to the PIM inhibitor AZD1208 and the FLT3 inhibitor AC220 in MV4-11 cell lines and MOLM-16 cell lines.

In MV4-11 cells, the IC₅₀ was 0.003 μM for AC220, 0.15 μM for SEL24-B489, and 2.24 μM for AZD1208. In MOLM-16 cells, the IC₅₀ was 0.07 μM for AZD1208, 0.1 μM for SEL24-B489, and >10 μM for AC220.

The researchers then evaluated SEL24-B489 in combination with cytarabine.

“The molecule shows very strong synergistic effects with cytarabine, both in vitro and in vivo,” Dr Brzózka said. “The combination index in vitro is approximately 0.1, 0.2. And in vivo, that translates to [nearly] 100% tumor growth inhibition.”

Tumor growth inhibition (TGI) measured 60% when mice received cytarabine alone at 50 mg/kg. TGI was 77% with SEL24-B489 alone at 25 mg/kg and 82% with SEL24-B489 alone at 50 mg/kg.

But with 25 mg/kg of SEL24-B489 and 50 mg/kg of cytarabine, TGI was 89%. And when both drugs were given at 50 mg/kg, TGI was 99%.

The researchers also assessed SEL24-B489 alone in mouse models of AML. In mice injected with MV4-11 cells, SEL24-B489 at 25 mg/kg BID reduced tumor volume by more than 50%, when compared to untreated control mice. And SEL24-B489 at 75 mg/kg BID reduced tumor volume by more than 80%.

In mice injected with MOLM-16 cells, SEL24-B489 at 25 mg/kg BID reduced tumor volume by more than 80%, when compared to untreated control mice. And SEL24-B489 at 75 mg/kg BID reduced tumor volume by more than 100%.

Finally, the team evaluated the safety of SEL24-B489 via repeated 5-day and 10-day toxicology studies in rats.

And they concluded that doses of 100 mg/kg QD x 5 and 25 mg/kg BID x 10 were safe, based on data concerning body weight gain, as well as results of clinical chemistry, hematology, necropsy, and histological analyses.

“Overall, SEL24-B489 has very good oral bioavailability and initial safety profiling,” Dr Brzózka said. “Both in vitro and in vivo, it shows a pretty promising therapeutic index.”

He and his colleagues are now studying SEL24-B489 in dogs, and Selvita is looking for a partner company to help move the drug to phase 1 trials.

*Information in the abstract differs from that presented at the meeting.

HOLLYWOOD, FLA. – The treatment of patients with lymphomatoid papulosis depends on the presentation, according to new National Comprehensive Cancer Network guidelines for managing primary cutaneous CD30+ T-cell lymphoproliferative disorders.

No treatment is needed in patients with lymphomatoid papulosis (LyP) who present without symptoms because spontaneous remission is extremely common in this disease, and these patients typically won’t have problems with progressive disease, Dr. Andrew D. Zelenetz said at the annual conference of the National Comprehensive Cancer Network.

For those who are symptomatic, topical or systemic treatments are useful in some cases.

Topical steroids "are effective, but not great," commented Dr. Zelenetz, vice chairman of medical informatics at Memorial Sloan Kettering Cancer Center, New York; professor of medicine at Cornell University, New York; and chair of the NCCN Non-Hodgkin's Lymphomas Guidelines panel.

Reported response rates are in the 50%-60% range, he said.

Bexarotene is another treatment option, although experience with this drug is quite limited. The largest series included only 11 patients. Unpublished data from that series at Memorial Sloan Kettering Cancer Center show a response rate of 45% at a maximum oral dose of 600 mg daily, Dr. Zelenetz said.

However, where this is a response, it is "dramatic and quite obvious," he noted, adding that treatment duration needs to be adequate before a patient is considered a nonresponder; the median duration of treatment in the 11-patient series was 35.5 weeks.

In a series of 57 patients from Memorial Sloan Kettering Cancer Center (including the 11 treated systemically with bexarotene), 16 received no therapy; 19 received topical treatment with steroids (13 patients), bexarotene (2 patients), UVB (2 patients), cryotherapy (1 patient), or nitrogen mustard (1 patient); and 5 received systemic treatment with methotrexate.

At follow-up, 14% of patients had no evidence of disease, and, with the exception of one who died of another cause, the remaining patients were alive with disease, Dr. Zelenetz said.

LyP is a rare CD30+ cutaneous lymphoproliferative disorder characterized by self-healing cropped or generalized eruptions of papules that come and go on the trunk or proximal extremities. In rare cases they present as solitary lesions.

"Even though many patients actually have intermittent recurrent disease ... the death rate from LyP is zero. So this is a very manageable disease; don’t overtreat these tumors," he said.

At the other end of the spectrum of CD30+ lymphoproliferative disorders addressed in the new NCCN guidelines is anaplastic large cell lymphoma (ALCL).

Primary cutaneous ALCL is characterized by skin-only presentation that is often localized but which can be disseminated in some cases. Lesions also tend to be larger and "more piled up" than those seen with LyP.

"You can get clustering in a specific area, but we don’t tend to have these big crops of lesions that we see with LyP," Dr. Zelenetz said.

The pathology is also different, with diffuse infiltration of the subcutaneous tissue. The cells are large and anaplastic, and there is intense expression of CD30.

The course of disease is usually indolent, with progression to extracutaneous sites in about 10%-15% of cases.

Nodules or tumors in cases of ALCL are less likely than LyP lesions to regress spontaneously, Dr. Zelenetz said.

This disease must be distinguished from a skin presentation of systemic ALCL, he noted.

"So what’s the big difference? In anaplastic large cell lymphoma that’s systemic, you will have multiple nodules all over and happen to have skin disease. With primary cutaneous ALCL, you have skin only or skin and some regional lymph nodes but nothing beyond that," he said, adding that these primary cutaneous tumors do extremely well nevertheless, with cumulative survival rates above 90%.

Those with systemic ALCL, however, have much lower cumulative survival, in the 25% range.

As with LyP, treatment for primary cutaneous ALCL is based on presentation.

For solitary or grouped lesions, the preferred treatment is surgical excision if needed for diagnosis or radiation if the diagnosis is already established.

Methotrexate is the preferred treatment for multifocal lesions.

The subtype that includes regional lymph nodes is typically treated with very mild chemotherapy including methotrexate or pralatrexate. Radiation can be used for locoregional disease, Dr. Zelenetz said.

An exception to the rule that patients with primary cutaneous ALCL do well is in cases of extensive limb disease. Patients with involvement of a single limb – usually lower extremity, but not always – have poor survival, and their disease is refractory to chemotherapy and radiation. It is unclear why there is a distinction in this presentation, but it is important to be aware of it, he said.

Dr. Zelenetz is a scientific adviser for Cancer Genetics Inc. and Gilead and has received consulting fees, honoraria, and/or grant or other research support from Celgene Corp., Cephalon Inc., Genentech Inc., GlaxoSmithKline, Roche Laboratories Inc., sanofi-aventis U.S., and Seattle Genetics Inc.

HOLLYWOOD, FLA. – The treatment of patients with lymphomatoid papulosis depends on the presentation, according to new National Comprehensive Cancer Network guidelines for managing primary cutaneous CD30+ T-cell lymphoproliferative disorders.

No treatment is needed in patients with lymphomatoid papulosis (LyP) who present without symptoms because spontaneous remission is extremely common in this disease, and these patients typically won’t have problems with progressive disease, Dr. Andrew D. Zelenetz said at the annual conference of the National Comprehensive Cancer Network.

For those who are symptomatic, topical or systemic treatments are useful in some cases.

Topical steroids "are effective, but not great," commented Dr. Zelenetz, vice chairman of medical informatics at Memorial Sloan Kettering Cancer Center, New York; professor of medicine at Cornell University, New York; and chair of the NCCN Non-Hodgkin's Lymphomas Guidelines panel.

Reported response rates are in the 50%-60% range, he said.

Bexarotene is another treatment option, although experience with this drug is quite limited. The largest series included only 11 patients. Unpublished data from that series at Memorial Sloan Kettering Cancer Center show a response rate of 45% at a maximum oral dose of 600 mg daily, Dr. Zelenetz said.

However, where this is a response, it is "dramatic and quite obvious," he noted, adding that treatment duration needs to be adequate before a patient is considered a nonresponder; the median duration of treatment in the 11-patient series was 35.5 weeks.

In a series of 57 patients from Memorial Sloan Kettering Cancer Center (including the 11 treated systemically with bexarotene), 16 received no therapy; 19 received topical treatment with steroids (13 patients), bexarotene (2 patients), UVB (2 patients), cryotherapy (1 patient), or nitrogen mustard (1 patient); and 5 received systemic treatment with methotrexate.

At follow-up, 14% of patients had no evidence of disease, and, with the exception of one who died of another cause, the remaining patients were alive with disease, Dr. Zelenetz said.

LyP is a rare CD30+ cutaneous lymphoproliferative disorder characterized by self-healing cropped or generalized eruptions of papules that come and go on the trunk or proximal extremities. In rare cases they present as solitary lesions.

"Even though many patients actually have intermittent recurrent disease ... the death rate from LyP is zero. So this is a very manageable disease; don’t overtreat these tumors," he said.

At the other end of the spectrum of CD30+ lymphoproliferative disorders addressed in the new NCCN guidelines is anaplastic large cell lymphoma (ALCL).

Primary cutaneous ALCL is characterized by skin-only presentation that is often localized but which can be disseminated in some cases. Lesions also tend to be larger and "more piled up" than those seen with LyP.

"You can get clustering in a specific area, but we don’t tend to have these big crops of lesions that we see with LyP," Dr. Zelenetz said.

The pathology is also different, with diffuse infiltration of the subcutaneous tissue. The cells are large and anaplastic, and there is intense expression of CD30.

The course of disease is usually indolent, with progression to extracutaneous sites in about 10%-15% of cases.

Nodules or tumors in cases of ALCL are less likely than LyP lesions to regress spontaneously, Dr. Zelenetz said.

This disease must be distinguished from a skin presentation of systemic ALCL, he noted.

"So what’s the big difference? In anaplastic large cell lymphoma that’s systemic, you will have multiple nodules all over and happen to have skin disease. With primary cutaneous ALCL, you have skin only or skin and some regional lymph nodes but nothing beyond that," he said, adding that these primary cutaneous tumors do extremely well nevertheless, with cumulative survival rates above 90%.

Those with systemic ALCL, however, have much lower cumulative survival, in the 25% range.

As with LyP, treatment for primary cutaneous ALCL is based on presentation.

For solitary or grouped lesions, the preferred treatment is surgical excision if needed for diagnosis or radiation if the diagnosis is already established.

Methotrexate is the preferred treatment for multifocal lesions.

The subtype that includes regional lymph nodes is typically treated with very mild chemotherapy including methotrexate or pralatrexate. Radiation can be used for locoregional disease, Dr. Zelenetz said.

An exception to the rule that patients with primary cutaneous ALCL do well is in cases of extensive limb disease. Patients with involvement of a single limb – usually lower extremity, but not always – have poor survival, and their disease is refractory to chemotherapy and radiation. It is unclear why there is a distinction in this presentation, but it is important to be aware of it, he said.

Dr. Zelenetz is a scientific adviser for Cancer Genetics Inc. and Gilead and has received consulting fees, honoraria, and/or grant or other research support from Celgene Corp., Cephalon Inc., Genentech Inc., GlaxoSmithKline, Roche Laboratories Inc., sanofi-aventis U.S., and Seattle Genetics Inc.

HOLLYWOOD, FLA. – The treatment of patients with lymphomatoid papulosis depends on the presentation, according to new National Comprehensive Cancer Network guidelines for managing primary cutaneous CD30+ T-cell lymphoproliferative disorders.

No treatment is needed in patients with lymphomatoid papulosis (LyP) who present without symptoms because spontaneous remission is extremely common in this disease, and these patients typically won’t have problems with progressive disease, Dr. Andrew D. Zelenetz said at the annual conference of the National Comprehensive Cancer Network.

For those who are symptomatic, topical or systemic treatments are useful in some cases.

Topical steroids "are effective, but not great," commented Dr. Zelenetz, vice chairman of medical informatics at Memorial Sloan Kettering Cancer Center, New York; professor of medicine at Cornell University, New York; and chair of the NCCN Non-Hodgkin's Lymphomas Guidelines panel.

Reported response rates are in the 50%-60% range, he said.

Bexarotene is another treatment option, although experience with this drug is quite limited. The largest series included only 11 patients. Unpublished data from that series at Memorial Sloan Kettering Cancer Center show a response rate of 45% at a maximum oral dose of 600 mg daily, Dr. Zelenetz said.

However, where this is a response, it is "dramatic and quite obvious," he noted, adding that treatment duration needs to be adequate before a patient is considered a nonresponder; the median duration of treatment in the 11-patient series was 35.5 weeks.

In a series of 57 patients from Memorial Sloan Kettering Cancer Center (including the 11 treated systemically with bexarotene), 16 received no therapy; 19 received topical treatment with steroids (13 patients), bexarotene (2 patients), UVB (2 patients), cryotherapy (1 patient), or nitrogen mustard (1 patient); and 5 received systemic treatment with methotrexate.

At follow-up, 14% of patients had no evidence of disease, and, with the exception of one who died of another cause, the remaining patients were alive with disease, Dr. Zelenetz said.

LyP is a rare CD30+ cutaneous lymphoproliferative disorder characterized by self-healing cropped or generalized eruptions of papules that come and go on the trunk or proximal extremities. In rare cases they present as solitary lesions.

"Even though many patients actually have intermittent recurrent disease ... the death rate from LyP is zero. So this is a very manageable disease; don’t overtreat these tumors," he said.

At the other end of the spectrum of CD30+ lymphoproliferative disorders addressed in the new NCCN guidelines is anaplastic large cell lymphoma (ALCL).

Primary cutaneous ALCL is characterized by skin-only presentation that is often localized but which can be disseminated in some cases. Lesions also tend to be larger and "more piled up" than those seen with LyP.

"You can get clustering in a specific area, but we don’t tend to have these big crops of lesions that we see with LyP," Dr. Zelenetz said.

The pathology is also different, with diffuse infiltration of the subcutaneous tissue. The cells are large and anaplastic, and there is intense expression of CD30.

The course of disease is usually indolent, with progression to extracutaneous sites in about 10%-15% of cases.

Nodules or tumors in cases of ALCL are less likely than LyP lesions to regress spontaneously, Dr. Zelenetz said.

This disease must be distinguished from a skin presentation of systemic ALCL, he noted.

"So what’s the big difference? In anaplastic large cell lymphoma that’s systemic, you will have multiple nodules all over and happen to have skin disease. With primary cutaneous ALCL, you have skin only or skin and some regional lymph nodes but nothing beyond that," he said, adding that these primary cutaneous tumors do extremely well nevertheless, with cumulative survival rates above 90%.

Those with systemic ALCL, however, have much lower cumulative survival, in the 25% range.

As with LyP, treatment for primary cutaneous ALCL is based on presentation.

For solitary or grouped lesions, the preferred treatment is surgical excision if needed for diagnosis or radiation if the diagnosis is already established.

Methotrexate is the preferred treatment for multifocal lesions.

The subtype that includes regional lymph nodes is typically treated with very mild chemotherapy including methotrexate or pralatrexate. Radiation can be used for locoregional disease, Dr. Zelenetz said.

An exception to the rule that patients with primary cutaneous ALCL do well is in cases of extensive limb disease. Patients with involvement of a single limb – usually lower extremity, but not always – have poor survival, and their disease is refractory to chemotherapy and radiation. It is unclear why there is a distinction in this presentation, but it is important to be aware of it, he said.

Dr. Zelenetz is a scientific adviser for Cancer Genetics Inc. and Gilead and has received consulting fees, honoraria, and/or grant or other research support from Celgene Corp., Cephalon Inc., Genentech Inc., GlaxoSmithKline, Roche Laboratories Inc., sanofi-aventis U.S., and Seattle Genetics Inc.

"Why do I need to do research if I’m going into private practice anyway?"

I have heard this question multiple times throughout my career as a resident, fellow, and attending thoracic surgeon. The truth is, there are multiple reasons, any of which is sufficient to justify your participation in clinical research during training. First, and perhaps most importantly, it teaches you to critically appraise the literature. This is a skill that will serve you well throughout your career, guiding your clinical decision-making, regardless if you choose private practice or academic surgery. Another reason is that performing clinical research allows you to become a content expert on a specific topic early in your career. This knowledge base is something that will serve as a foundation for ongoing learning and may help in designing future studies. Once your project is complete, it will be your ticket to attend and present at regional, national, or international meetings. There is no better forum to gain public recognition for your investigative efforts and network with potential future partners than societal meetings. Formal and informal interviews routinely occur at these gatherings and you do not want to be left out because you chose not to participate in research as a trainee. Finally, it is your responsibility to the patients that you have sworn to treat. There are many ways to care for patients, and pushing back the frontiers of medical knowledge is as important as the day-to-day tasks that you perform on the ward or in the operating room.

So, now that you have decided that you want to participate in a research project as a trainee, how do you make it happen? Before you begin a project, you will have to choose a mentor, a topic, a clear, novel question, and the appropriate study design. Chances are that at some point, a mentor helped guide you toward a career in cardiothoracic surgery. A research mentor is just as important as a clinical mentor for a young surgeon.

The most important trait that you should seek out in a research mentor is the ability to delineate important questions. All too often, residents and fellows are approached by attending surgeons with good intentions, but bad research ideas. Trainees then feel obligated to take them up on the project (in order to not appear like a slacker) and for various reasons, it does not result in an abstract, presentation, or publication. In fact, all it results in is frustration, a distaste for investigation, and wasted time. The bottom line is that only you can protect your time, and as a surgical trainee, you must guard it ferociously. Look for a mentor who is an expert in your field of interest and who has a track record of publications.

He or she must be a logical thinker who can help you delineate a clear, novel question, choose the appropriate study design, guide your writing of the manuscript, and direct your submission to the appropriate meetings and journals. Finally, your mentor must be dedicated to your success. We are all busy, but if your mentor cannot find the time to routinely meet with you at every step of your project, you need to find a new mentor.

Choosing a clear, novel clinical question starts with choosing an appropriate topic (Table 1). With the right topic and question, the hypothesis is obvious, it is easy to define your endpoints, and your study design will fall into place. But with the wrong question, your study will lack focus, it will be difficult to explain the relevance of your study, and you will not want to present your data on the podium. An example of a good question is "Do patients with a given disease treated with operation X live longer than those treated with operation Y?" Stay away from the lure of "Let’s review our experience of operation X..." or "Why don’t I see how many of operation Y we’ve done over the past 10 years..." These topics are vague and do not ask a specific question. There must be a clear hypothesis for any study that is expected to produce meaningful results.

Once you have chosen an appropriate question, you must decide on a study design. Although case reports are marginally publishable, they will not answer your clinical questions. For many reasons, randomized, controlled trials, the gold standard of research, are difficult to design, carry out, and complete in your short time as a trainee. The good news is that well-designed and sufficiently powered observational studies often give similar results as randomized, controlled studies. Examples of common observational study designs include cohort studies, case control studies, and cross-sectional studies (Table 2). Each study design is different and your mentor should be able to help you decide which is the best to answer the question you want to ask.

When designing a study, one of the most important principles is defining a priori endpoints. Every study will have one primary endpoint that reflects the hypothesis. Secondary endpoints are interesting and potentially helpful, but are not the main message. It will be important to meet with a statistician before you start data collection. Understanding the statistics to be used will allow you to collect your data in the correct way (categorical vs. continuous, etc.). Reviewing charts is very time consuming and you have to do everything in your power to ensure you only do it once.

The next step is to create a research proposal. To do this, you will need to go to the literature, and see what published data relate to your study. Perhaps there are previous studies examining your question with conflicting results. Or if your question has not been previously investigated, what supporting literature suggests that yours is the next logical study? Your proposal should include a background section (1-2 paragraphs), hypothesis (1 sentence), the specific aims of the study (1-3 sentences), methods (2-4 paragraphs), anticipated results (1 paragraph), proposed timeline, and anticipated meeting to which it will be submitted. Your mentor will revise and critique the proposal and eventually give you a signature of approval.

This proposal serves many purposes. It will allow you to fully understand the study before you begin, some form of it is usually required for the Institutional Review Board (IRB) application, it will serve as the outline for your eventual manuscript, and it sets a timeline for completion of the project. Without an agreed upon deadline, too many good studies are left in various states of completion when the trainee moves on, and are never finished. The deadline should be based on the meeting that you and your mentor agree is appropriate for reporting your results.

Most would agree that data collection is the most painful part of doing clinical research. However, there are a few tricks to ease your pain. First, there are many databases available that you may be able to harvest data from to minimize your chart work (Table 3). Before you hit the charts, it is essential to think through every step of the project.

Anticipate problems (where in the chart will you locate each data point), do not collect unnecessary data points (postoperative data #3 serum [Na⁺] when looking at survival of thoracoscopic vs. open lobectomy), meet with your statistician beforehand to collect data for the correct analysis, collect the raw data (creatinine and weight, not presence of renal failure and obesity). Finally, be sure that your data are backed up in multiple places. Some prefer to collect data on paper then enter it later into a spreadsheet. This ensures a hard copy of the data regardless of whether the electronic version is lost.

After the data are collected and the statistics are done, you will be faced with interpreting your results and composing an abstract and manuscript. If your study is focused and hypothesis driven, this step should be fairly straightforward.

Schedule time with your mentor and discuss the results to ensure your interpretation of the data is correct. Next, using your proposal as an outline, put together a rough draft of a manuscript.

Remember that manuscripts are the currency of academia. If you do not present and publish your work, you have not fully capitalized on the hard work you have put in to your study. Your mentor will need to revise your manuscript repeatedly; use it as a learning experience for critiquing the literature and writing future manuscripts. He or she likely knows what editors and readers will be looking for in your finished product.

Remember, you will need multiple revisions of the abstract and manuscript, so plan adequate time prior to your deadline for writing. Most institutions have medical illustrators available for hire; consider including a drawing or photograph if it legitimately adds content to your manuscript.

The final step in the process is presenting your work in front of experts who likely know more about cardiothoracic surgery than you. Just remember, no one knows more about your data than you. Prepare relentlessly for your talk, take a deep breath before you walk on stage, speak with confidence, and if you don’t know the answer to a given question from the audience, admit it. Soon enough you will be the expert in the audience asking the tough questions.

Then spend as much time as possible after the session speaking with audience members about you and your study. You will meet lifelong colleagues, and maybe even your future partner. For many, research is a rewarding lifelong endeavor. For others, it is a means of learning to critically appraise the literature and landing a job. Either way, you cannot afford not to do research as a trainee.

Acknowledgement: I would like to thank my friend and colleague, Dr. Stephen H. McKellar (University of Utah), for his advice on performing research as a cardiothoracic trainee.

Dr. Seder is in the department of cardiovascular and thoracic surgery at Rush University Medical Center.

"Why do I need to do research if I’m going into private practice anyway?"

I have heard this question multiple times throughout my career as a resident, fellow, and attending thoracic surgeon. The truth is, there are multiple reasons, any of which is sufficient to justify your participation in clinical research during training. First, and perhaps most importantly, it teaches you to critically appraise the literature. This is a skill that will serve you well throughout your career, guiding your clinical decision-making, regardless if you choose private practice or academic surgery. Another reason is that performing clinical research allows you to become a content expert on a specific topic early in your career. This knowledge base is something that will serve as a foundation for ongoing learning and may help in designing future studies. Once your project is complete, it will be your ticket to attend and present at regional, national, or international meetings. There is no better forum to gain public recognition for your investigative efforts and network with potential future partners than societal meetings. Formal and informal interviews routinely occur at these gatherings and you do not want to be left out because you chose not to participate in research as a trainee. Finally, it is your responsibility to the patients that you have sworn to treat. There are many ways to care for patients, and pushing back the frontiers of medical knowledge is as important as the day-to-day tasks that you perform on the ward or in the operating room.

So, now that you have decided that you want to participate in a research project as a trainee, how do you make it happen? Before you begin a project, you will have to choose a mentor, a topic, a clear, novel question, and the appropriate study design. Chances are that at some point, a mentor helped guide you toward a career in cardiothoracic surgery. A research mentor is just as important as a clinical mentor for a young surgeon.

The most important trait that you should seek out in a research mentor is the ability to delineate important questions. All too often, residents and fellows are approached by attending surgeons with good intentions, but bad research ideas. Trainees then feel obligated to take them up on the project (in order to not appear like a slacker) and for various reasons, it does not result in an abstract, presentation, or publication. In fact, all it results in is frustration, a distaste for investigation, and wasted time. The bottom line is that only you can protect your time, and as a surgical trainee, you must guard it ferociously. Look for a mentor who is an expert in your field of interest and who has a track record of publications.

He or she must be a logical thinker who can help you delineate a clear, novel question, choose the appropriate study design, guide your writing of the manuscript, and direct your submission to the appropriate meetings and journals. Finally, your mentor must be dedicated to your success. We are all busy, but if your mentor cannot find the time to routinely meet with you at every step of your project, you need to find a new mentor.

Choosing a clear, novel clinical question starts with choosing an appropriate topic (Table 1). With the right topic and question, the hypothesis is obvious, it is easy to define your endpoints, and your study design will fall into place. But with the wrong question, your study will lack focus, it will be difficult to explain the relevance of your study, and you will not want to present your data on the podium. An example of a good question is "Do patients with a given disease treated with operation X live longer than those treated with operation Y?" Stay away from the lure of "Let’s review our experience of operation X..." or "Why don’t I see how many of operation Y we’ve done over the past 10 years..." These topics are vague and do not ask a specific question. There must be a clear hypothesis for any study that is expected to produce meaningful results.

Once you have chosen an appropriate question, you must decide on a study design. Although case reports are marginally publishable, they will not answer your clinical questions. For many reasons, randomized, controlled trials, the gold standard of research, are difficult to design, carry out, and complete in your short time as a trainee. The good news is that well-designed and sufficiently powered observational studies often give similar results as randomized, controlled studies. Examples of common observational study designs include cohort studies, case control studies, and cross-sectional studies (Table 2). Each study design is different and your mentor should be able to help you decide which is the best to answer the question you want to ask.

When designing a study, one of the most important principles is defining a priori endpoints. Every study will have one primary endpoint that reflects the hypothesis. Secondary endpoints are interesting and potentially helpful, but are not the main message. It will be important to meet with a statistician before you start data collection. Understanding the statistics to be used will allow you to collect your data in the correct way (categorical vs. continuous, etc.). Reviewing charts is very time consuming and you have to do everything in your power to ensure you only do it once.

The next step is to create a research proposal. To do this, you will need to go to the literature, and see what published data relate to your study. Perhaps there are previous studies examining your question with conflicting results. Or if your question has not been previously investigated, what supporting literature suggests that yours is the next logical study? Your proposal should include a background section (1-2 paragraphs), hypothesis (1 sentence), the specific aims of the study (1-3 sentences), methods (2-4 paragraphs), anticipated results (1 paragraph), proposed timeline, and anticipated meeting to which it will be submitted. Your mentor will revise and critique the proposal and eventually give you a signature of approval.

This proposal serves many purposes. It will allow you to fully understand the study before you begin, some form of it is usually required for the Institutional Review Board (IRB) application, it will serve as the outline for your eventual manuscript, and it sets a timeline for completion of the project. Without an agreed upon deadline, too many good studies are left in various states of completion when the trainee moves on, and are never finished. The deadline should be based on the meeting that you and your mentor agree is appropriate for reporting your results.

Most would agree that data collection is the most painful part of doing clinical research. However, there are a few tricks to ease your pain. First, there are many databases available that you may be able to harvest data from to minimize your chart work (Table 3). Before you hit the charts, it is essential to think through every step of the project.

Anticipate problems (where in the chart will you locate each data point), do not collect unnecessary data points (postoperative data #3 serum [Na⁺] when looking at survival of thoracoscopic vs. open lobectomy), meet with your statistician beforehand to collect data for the correct analysis, collect the raw data (creatinine and weight, not presence of renal failure and obesity). Finally, be sure that your data are backed up in multiple places. Some prefer to collect data on paper then enter it later into a spreadsheet. This ensures a hard copy of the data regardless of whether the electronic version is lost.

After the data are collected and the statistics are done, you will be faced with interpreting your results and composing an abstract and manuscript. If your study is focused and hypothesis driven, this step should be fairly straightforward.

Schedule time with your mentor and discuss the results to ensure your interpretation of the data is correct. Next, using your proposal as an outline, put together a rough draft of a manuscript.

Remember that manuscripts are the currency of academia. If you do not present and publish your work, you have not fully capitalized on the hard work you have put in to your study. Your mentor will need to revise your manuscript repeatedly; use it as a learning experience for critiquing the literature and writing future manuscripts. He or she likely knows what editors and readers will be looking for in your finished product.

Remember, you will need multiple revisions of the abstract and manuscript, so plan adequate time prior to your deadline for writing. Most institutions have medical illustrators available for hire; consider including a drawing or photograph if it legitimately adds content to your manuscript.

The final step in the process is presenting your work in front of experts who likely know more about cardiothoracic surgery than you. Just remember, no one knows more about your data than you. Prepare relentlessly for your talk, take a deep breath before you walk on stage, speak with confidence, and if you don’t know the answer to a given question from the audience, admit it. Soon enough you will be the expert in the audience asking the tough questions.

Then spend as much time as possible after the session speaking with audience members about you and your study. You will meet lifelong colleagues, and maybe even your future partner. For many, research is a rewarding lifelong endeavor. For others, it is a means of learning to critically appraise the literature and landing a job. Either way, you cannot afford not to do research as a trainee.

Acknowledgement: I would like to thank my friend and colleague, Dr. Stephen H. McKellar (University of Utah), for his advice on performing research as a cardiothoracic trainee.

Dr. Seder is in the department of cardiovascular and thoracic surgery at Rush University Medical Center.

"Why do I need to do research if I’m going into private practice anyway?"

I have heard this question multiple times throughout my career as a resident, fellow, and attending thoracic surgeon. The truth is, there are multiple reasons, any of which is sufficient to justify your participation in clinical research during training. First, and perhaps most importantly, it teaches you to critically appraise the literature. This is a skill that will serve you well throughout your career, guiding your clinical decision-making, regardless if you choose private practice or academic surgery. Another reason is that performing clinical research allows you to become a content expert on a specific topic early in your career. This knowledge base is something that will serve as a foundation for ongoing learning and may help in designing future studies. Once your project is complete, it will be your ticket to attend and present at regional, national, or international meetings. There is no better forum to gain public recognition for your investigative efforts and network with potential future partners than societal meetings. Formal and informal interviews routinely occur at these gatherings and you do not want to be left out because you chose not to participate in research as a trainee. Finally, it is your responsibility to the patients that you have sworn to treat. There are many ways to care for patients, and pushing back the frontiers of medical knowledge is as important as the day-to-day tasks that you perform on the ward or in the operating room.

So, now that you have decided that you want to participate in a research project as a trainee, how do you make it happen? Before you begin a project, you will have to choose a mentor, a topic, a clear, novel question, and the appropriate study design. Chances are that at some point, a mentor helped guide you toward a career in cardiothoracic surgery. A research mentor is just as important as a clinical mentor for a young surgeon.

The most important trait that you should seek out in a research mentor is the ability to delineate important questions. All too often, residents and fellows are approached by attending surgeons with good intentions, but bad research ideas. Trainees then feel obligated to take them up on the project (in order to not appear like a slacker) and for various reasons, it does not result in an abstract, presentation, or publication. In fact, all it results in is frustration, a distaste for investigation, and wasted time. The bottom line is that only you can protect your time, and as a surgical trainee, you must guard it ferociously. Look for a mentor who is an expert in your field of interest and who has a track record of publications.

He or she must be a logical thinker who can help you delineate a clear, novel question, choose the appropriate study design, guide your writing of the manuscript, and direct your submission to the appropriate meetings and journals. Finally, your mentor must be dedicated to your success. We are all busy, but if your mentor cannot find the time to routinely meet with you at every step of your project, you need to find a new mentor.

Choosing a clear, novel clinical question starts with choosing an appropriate topic (Table 1). With the right topic and question, the hypothesis is obvious, it is easy to define your endpoints, and your study design will fall into place. But with the wrong question, your study will lack focus, it will be difficult to explain the relevance of your study, and you will not want to present your data on the podium. An example of a good question is "Do patients with a given disease treated with operation X live longer than those treated with operation Y?" Stay away from the lure of "Let’s review our experience of operation X..." or "Why don’t I see how many of operation Y we’ve done over the past 10 years..." These topics are vague and do not ask a specific question. There must be a clear hypothesis for any study that is expected to produce meaningful results.

Once you have chosen an appropriate question, you must decide on a study design. Although case reports are marginally publishable, they will not answer your clinical questions. For many reasons, randomized, controlled trials, the gold standard of research, are difficult to design, carry out, and complete in your short time as a trainee. The good news is that well-designed and sufficiently powered observational studies often give similar results as randomized, controlled studies. Examples of common observational study designs include cohort studies, case control studies, and cross-sectional studies (Table 2). Each study design is different and your mentor should be able to help you decide which is the best to answer the question you want to ask.

When designing a study, one of the most important principles is defining a priori endpoints. Every study will have one primary endpoint that reflects the hypothesis. Secondary endpoints are interesting and potentially helpful, but are not the main message. It will be important to meet with a statistician before you start data collection. Understanding the statistics to be used will allow you to collect your data in the correct way (categorical vs. continuous, etc.). Reviewing charts is very time consuming and you have to do everything in your power to ensure you only do it once.

The next step is to create a research proposal. To do this, you will need to go to the literature, and see what published data relate to your study. Perhaps there are previous studies examining your question with conflicting results. Or if your question has not been previously investigated, what supporting literature suggests that yours is the next logical study? Your proposal should include a background section (1-2 paragraphs), hypothesis (1 sentence), the specific aims of the study (1-3 sentences), methods (2-4 paragraphs), anticipated results (1 paragraph), proposed timeline, and anticipated meeting to which it will be submitted. Your mentor will revise and critique the proposal and eventually give you a signature of approval.

This proposal serves many purposes. It will allow you to fully understand the study before you begin, some form of it is usually required for the Institutional Review Board (IRB) application, it will serve as the outline for your eventual manuscript, and it sets a timeline for completion of the project. Without an agreed upon deadline, too many good studies are left in various states of completion when the trainee moves on, and are never finished. The deadline should be based on the meeting that you and your mentor agree is appropriate for reporting your results.

Most would agree that data collection is the most painful part of doing clinical research. However, there are a few tricks to ease your pain. First, there are many databases available that you may be able to harvest data from to minimize your chart work (Table 3). Before you hit the charts, it is essential to think through every step of the project.

Anticipate problems (where in the chart will you locate each data point), do not collect unnecessary data points (postoperative data #3 serum [Na⁺] when looking at survival of thoracoscopic vs. open lobectomy), meet with your statistician beforehand to collect data for the correct analysis, collect the raw data (creatinine and weight, not presence of renal failure and obesity). Finally, be sure that your data are backed up in multiple places. Some prefer to collect data on paper then enter it later into a spreadsheet. This ensures a hard copy of the data regardless of whether the electronic version is lost.

After the data are collected and the statistics are done, you will be faced with interpreting your results and composing an abstract and manuscript. If your study is focused and hypothesis driven, this step should be fairly straightforward.

Schedule time with your mentor and discuss the results to ensure your interpretation of the data is correct. Next, using your proposal as an outline, put together a rough draft of a manuscript.

Remember that manuscripts are the currency of academia. If you do not present and publish your work, you have not fully capitalized on the hard work you have put in to your study. Your mentor will need to revise your manuscript repeatedly; use it as a learning experience for critiquing the literature and writing future manuscripts. He or she likely knows what editors and readers will be looking for in your finished product.

Remember, you will need multiple revisions of the abstract and manuscript, so plan adequate time prior to your deadline for writing. Most institutions have medical illustrators available for hire; consider including a drawing or photograph if it legitimately adds content to your manuscript.

The final step in the process is presenting your work in front of experts who likely know more about cardiothoracic surgery than you. Just remember, no one knows more about your data than you. Prepare relentlessly for your talk, take a deep breath before you walk on stage, speak with confidence, and if you don’t know the answer to a given question from the audience, admit it. Soon enough you will be the expert in the audience asking the tough questions.

Then spend as much time as possible after the session speaking with audience members about you and your study. You will meet lifelong colleagues, and maybe even your future partner. For many, research is a rewarding lifelong endeavor. For others, it is a means of learning to critically appraise the literature and landing a job. Either way, you cannot afford not to do research as a trainee.

Acknowledgement: I would like to thank my friend and colleague, Dr. Stephen H. McKellar (University of Utah), for his advice on performing research as a cardiothoracic trainee.

Dr. Seder is in the department of cardiovascular and thoracic surgery at Rush University Medical Center.

Injection of botulinum toxin type A continues to be the most popular form of minimally invasive cosmetic surgery, with a total of more than 6.3 million procedures performed in 2013, the American Society of Plastic Surgeons reported.

Overall, botulinum toxins such as Botox and Dysport accounted for 47% of the market for minimally invasive procedures, which totaled 13.4 million procedures in 2013, according to the ASPS.

The second most popular surgery was injection of soft tissue fillers, with 2.2 million procedures performed, followed by chemical peels (1.2 million procedures), laser hair removal (1.1 million), and microdermabrasion (970,000), the ASPS said.

The total number of minimally invasive procedures increased by 3% from 2012, as did the number of botulinum injections. The largest increase for a single type of procedure was seen for the soft tissue fillers, with hyaluronic acid injections up 18% from 2012 to 2013, the ASPS noted.

The estimates for 2013 are based on data from a national database and survey responses from 800 dermatologists, ENTs, and plastic surgeons.

[email protected]

Injection of botulinum toxin type A continues to be the most popular form of minimally invasive cosmetic surgery, with a total of more than 6.3 million procedures performed in 2013, the American Society of Plastic Surgeons reported.

Overall, botulinum toxins such as Botox and Dysport accounted for 47% of the market for minimally invasive procedures, which totaled 13.4 million procedures in 2013, according to the ASPS.

The second most popular surgery was injection of soft tissue fillers, with 2.2 million procedures performed, followed by chemical peels (1.2 million procedures), laser hair removal (1.1 million), and microdermabrasion (970,000), the ASPS said.

The total number of minimally invasive procedures increased by 3% from 2012, as did the number of botulinum injections. The largest increase for a single type of procedure was seen for the soft tissue fillers, with hyaluronic acid injections up 18% from 2012 to 2013, the ASPS noted.

The estimates for 2013 are based on data from a national database and survey responses from 800 dermatologists, ENTs, and plastic surgeons.

[email protected]

Injection of botulinum toxin type A continues to be the most popular form of minimally invasive cosmetic surgery, with a total of more than 6.3 million procedures performed in 2013, the American Society of Plastic Surgeons reported.

Overall, botulinum toxins such as Botox and Dysport accounted for 47% of the market for minimally invasive procedures, which totaled 13.4 million procedures in 2013, according to the ASPS.

The second most popular surgery was injection of soft tissue fillers, with 2.2 million procedures performed, followed by chemical peels (1.2 million procedures), laser hair removal (1.1 million), and microdermabrasion (970,000), the ASPS said.

The total number of minimally invasive procedures increased by 3% from 2012, as did the number of botulinum injections. The largest increase for a single type of procedure was seen for the soft tissue fillers, with hyaluronic acid injections up 18% from 2012 to 2013, the ASPS noted.

The estimates for 2013 are based on data from a national database and survey responses from 800 dermatologists, ENTs, and plastic surgeons.

[email protected]

It was the worst of days. It was the best of days.

When I opened the mail one day last week, I found a letter from someone I’ll call Thelma. It read, in part:

"Last Monday you were kind enough to look at my rash, which you thought was just eczema. You gave me cream and asked me to e-mail you Thursday about my condition. When I did and said I was still itchy, you said I should stick with the same and that I could come back Monday, but I couldn’t wait because I itched so bad I couldn’t take it anymore. I saw another doctor Friday who said the patch was host to something called pityriasis rosea. He said the rash was so textbook it should have been picked up immediately. I had to be put on an oral steroid right away.

"I am so upset that I’m sending you back your bill [for a $15 co-pay] because I had to go to another doctor who could really help me."

I thought of a few choice words for my esteemed Friday colleague, but kept them to myself. A single scaly patch is a textbook case of pityriasis rosea? Oral steroids for pityriasis? Really?

As far as this patient is concerned, I must be a bum. Thirty-five years on the job, and I haven’t mastered the textbook yet.

Sunk in gloom, I opened an e-mail sent to my website by a patient I’ll call Louise:

"I suffer from psoriasis and have been to countless dermatologists since I was 8 years old. I recently had a terrible outbreak and was really hesitant to even go to a dermatologist because I’ve never been satisfied with any of them. Your associate is wonderful! I can’t say enough about her. She is warm, thorough, and really takes the time to sit with you and listen. You can tell she truly cares about her patients and loves her job."

I looked at the patient’s chart. What was the wonderful and satisfying treatment that my associate had prescribed to deal with this patient’s lifelong, recalcitrant psoriasis?

Betamethasone dipropionate cream 0.05%. Wow.

I e-mailed my associate at once and we shared a gratified chuckle. Guess no one ever thought of treating Louise’s psoriasis with a topical steroid before. We must be geniuses, right out there on the cutting edge.

So which are we, dear colleagues – geniuses or bums?

We’re neither, of course, which doesn’t stop our patients from forming firm opinions one way or the other. Which they can share by angry letter, fulsome e-mail, or, of course, any on-line reviews they can slip past the mysterious algorithms of the Yelps and Angie’s Lists of the world.

When I get messages like Thelma’s and Louise’s, I show them to my students and make three suggestions:

• Don’t try to look smart at someone else’s expense. Next time around a patient will be in somebody else’s office calling you a fool.

• Don’t respond to snippy patients’ complaints by contacting the complainer and trying to justify yourself. Learn something if you can, and move on.

• Be grateful for praise. Just don’t take it too seriously.

In the meantime, the insurers and assorted bureaucrats who run our lives these days are busy defining good care and claiming to measure it so they can reward quality and punish inefficiency. I’m sure they think they’re doing a fine job, although I remain deeply skeptical that what they choose to measure has much relevance to what actually goes on in offices like ours.

I could, of course, try to tell them why I think so. (I have tried, in fact.) Getting through to people with a completely different way of looking at things than yours is not very rewarding, even when large sums of money are not involved. I would have as good a chance of winning them over as I would of convincing Thelma that a scaly patch is not textbook pityriasis that needs prednisone and Louise that betamethasone cream is not the breakthrough that will change her life.

So: Not the best of times. Not the worst of times. Just another day at the office.

Dr. Rockoff practices dermatology in Brookline, Mass. He is on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. Dr. Rockoff has contributed to the Under My Skin column in Skin & Allergy News since 1997.

It was the worst of days. It was the best of days.

When I opened the mail one day last week, I found a letter from someone I’ll call Thelma. It read, in part:

"Last Monday you were kind enough to look at my rash, which you thought was just eczema. You gave me cream and asked me to e-mail you Thursday about my condition. When I did and said I was still itchy, you said I should stick with the same and that I could come back Monday, but I couldn’t wait because I itched so bad I couldn’t take it anymore. I saw another doctor Friday who said the patch was host to something called pityriasis rosea. He said the rash was so textbook it should have been picked up immediately. I had to be put on an oral steroid right away.

"I am so upset that I’m sending you back your bill [for a $15 co-pay] because I had to go to another doctor who could really help me."

I thought of a few choice words for my esteemed Friday colleague, but kept them to myself. A single scaly patch is a textbook case of pityriasis rosea? Oral steroids for pityriasis? Really?

As far as this patient is concerned, I must be a bum. Thirty-five years on the job, and I haven’t mastered the textbook yet.

Sunk in gloom, I opened an e-mail sent to my website by a patient I’ll call Louise:

"I suffer from psoriasis and have been to countless dermatologists since I was 8 years old. I recently had a terrible outbreak and was really hesitant to even go to a dermatologist because I’ve never been satisfied with any of them. Your associate is wonderful! I can’t say enough about her. She is warm, thorough, and really takes the time to sit with you and listen. You can tell she truly cares about her patients and loves her job."

I looked at the patient’s chart. What was the wonderful and satisfying treatment that my associate had prescribed to deal with this patient’s lifelong, recalcitrant psoriasis?

Betamethasone dipropionate cream 0.05%. Wow.

I e-mailed my associate at once and we shared a gratified chuckle. Guess no one ever thought of treating Louise’s psoriasis with a topical steroid before. We must be geniuses, right out there on the cutting edge.

So which are we, dear colleagues – geniuses or bums?

We’re neither, of course, which doesn’t stop our patients from forming firm opinions one way or the other. Which they can share by angry letter, fulsome e-mail, or, of course, any on-line reviews they can slip past the mysterious algorithms of the Yelps and Angie’s Lists of the world.

When I get messages like Thelma’s and Louise’s, I show them to my students and make three suggestions:

• Don’t try to look smart at someone else’s expense. Next time around a patient will be in somebody else’s office calling you a fool.

• Don’t respond to snippy patients’ complaints by contacting the complainer and trying to justify yourself. Learn something if you can, and move on.

• Be grateful for praise. Just don’t take it too seriously.

In the meantime, the insurers and assorted bureaucrats who run our lives these days are busy defining good care and claiming to measure it so they can reward quality and punish inefficiency. I’m sure they think they’re doing a fine job, although I remain deeply skeptical that what they choose to measure has much relevance to what actually goes on in offices like ours.

I could, of course, try to tell them why I think so. (I have tried, in fact.) Getting through to people with a completely different way of looking at things than yours is not very rewarding, even when large sums of money are not involved. I would have as good a chance of winning them over as I would of convincing Thelma that a scaly patch is not textbook pityriasis that needs prednisone and Louise that betamethasone cream is not the breakthrough that will change her life.

So: Not the best of times. Not the worst of times. Just another day at the office.

Dr. Rockoff practices dermatology in Brookline, Mass. He is on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. Dr. Rockoff has contributed to the Under My Skin column in Skin & Allergy News since 1997.

It was the worst of days. It was the best of days.

When I opened the mail one day last week, I found a letter from someone I’ll call Thelma. It read, in part:

"Last Monday you were kind enough to look at my rash, which you thought was just eczema. You gave me cream and asked me to e-mail you Thursday about my condition. When I did and said I was still itchy, you said I should stick with the same and that I could come back Monday, but I couldn’t wait because I itched so bad I couldn’t take it anymore. I saw another doctor Friday who said the patch was host to something called pityriasis rosea. He said the rash was so textbook it should have been picked up immediately. I had to be put on an oral steroid right away.

"I am so upset that I’m sending you back your bill [for a $15 co-pay] because I had to go to another doctor who could really help me."

I thought of a few choice words for my esteemed Friday colleague, but kept them to myself. A single scaly patch is a textbook case of pityriasis rosea? Oral steroids for pityriasis? Really?

As far as this patient is concerned, I must be a bum. Thirty-five years on the job, and I haven’t mastered the textbook yet.

Sunk in gloom, I opened an e-mail sent to my website by a patient I’ll call Louise:

"I suffer from psoriasis and have been to countless dermatologists since I was 8 years old. I recently had a terrible outbreak and was really hesitant to even go to a dermatologist because I’ve never been satisfied with any of them. Your associate is wonderful! I can’t say enough about her. She is warm, thorough, and really takes the time to sit with you and listen. You can tell she truly cares about her patients and loves her job."

I looked at the patient’s chart. What was the wonderful and satisfying treatment that my associate had prescribed to deal with this patient’s lifelong, recalcitrant psoriasis?

Betamethasone dipropionate cream 0.05%. Wow.

I e-mailed my associate at once and we shared a gratified chuckle. Guess no one ever thought of treating Louise’s psoriasis with a topical steroid before. We must be geniuses, right out there on the cutting edge.

So which are we, dear colleagues – geniuses or bums?

We’re neither, of course, which doesn’t stop our patients from forming firm opinions one way or the other. Which they can share by angry letter, fulsome e-mail, or, of course, any on-line reviews they can slip past the mysterious algorithms of the Yelps and Angie’s Lists of the world.

When I get messages like Thelma’s and Louise’s, I show them to my students and make three suggestions:

• Don’t try to look smart at someone else’s expense. Next time around a patient will be in somebody else’s office calling you a fool.

• Don’t respond to snippy patients’ complaints by contacting the complainer and trying to justify yourself. Learn something if you can, and move on.

• Be grateful for praise. Just don’t take it too seriously.

In the meantime, the insurers and assorted bureaucrats who run our lives these days are busy defining good care and claiming to measure it so they can reward quality and punish inefficiency. I’m sure they think they’re doing a fine job, although I remain deeply skeptical that what they choose to measure has much relevance to what actually goes on in offices like ours.

I could, of course, try to tell them why I think so. (I have tried, in fact.) Getting through to people with a completely different way of looking at things than yours is not very rewarding, even when large sums of money are not involved. I would have as good a chance of winning them over as I would of convincing Thelma that a scaly patch is not textbook pityriasis that needs prednisone and Louise that betamethasone cream is not the breakthrough that will change her life.

So: Not the best of times. Not the worst of times. Just another day at the office.

Dr. Rockoff practices dermatology in Brookline, Mass. He is on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. Dr. Rockoff has contributed to the Under My Skin column in Skin & Allergy News since 1997.