Article

Type 2 diabetes has been increasing in incidence and prevalence over the past 20 years, with worldwide prevalence estimated at 6.28%.¹ The estimated cost of diagnosed diabetes in the United States was $327 billion in 2017; this included direct medical costs and reduced productivity.² Type 2 diabetes can be prevented in most patients, given that it is a metabolic derangement caused by a complicated interaction between a patient’s genetic predisposition and lifestyle. A consensus statement by the American Academy of Clinical Endocrinologists (AACE) and American College of Endocrinology indicates that the recommended lifestyle modifications for diabetes include medical nutrition therapy with healthy eating patterns, regular physical activity, adequate sleep, behavioral support/counseling, and smoking cessation.³ Evidence shows that adherence to these lifestyle changes alone yields a relative reduction in type 2 diabetes mortality of 57%.⁴

IMAGE: ©ALICIA BUELOW; PATIENT IMAGE © GETTY IMAGES

In the discussion that follows, we review the current guideline recommendations for dietary modifications and physical activity and summarize their effectiveness in the treatment of type 2 diabetes. We also describe practical clinical strategies to promote change in patient behavior, and examine current literature supporting intensive lifestyle changes that, if achieved, may induce disease remission.⁵

Dietary strategies

Low, or very low, carbohydrate diet  

Carbohydrates can affect blood glucose levels in varying degrees depending on their intrinsic properties such as fiber content, sugars, and starches . ⁶ According to the American Diabetes Association’s (ADA) 2019 consensus report, ⁶ the carbohydrate quality that generally should be recommended is high in fiber, vitamins, and minerals, and low in added sugars, fats, and sodium (processed carbohydrates) ( TABLE 1 ^7-10 ). A low-carbohydrate diet (LCD) typically has a carbohydrate content < 130 g/d or < 26% of a 2000 kcal/d diet. ¹¹ A very low–carbohydrate diet (VLCD) is 20-50 g/d or < 10% of the 2000 kcal/day diet. ¹¹

Adherence to lifestyle changes alone yields a relative reduction in type 2 diabetes mortality of 57%.

In a meta-analysis by Goldenberg et al¹¹, the LCD was shown to reduce A1C by 0.47% at 6 months (95% CI, –0.6 to –0.34) and by 0.23% at 12 months when compared with control diets. A review of multiple meta-­analyses also showed a significant reduction in A1C especially with VLCD patterns; however, the results waned at the 12-month follow-up.⁵ In addition, confounding factors were seen when comparing adherence between LCD and VLCD, with patients in the latter group having larger problems with adherence, which decreased the benefit seen in the overall group comparison.¹¹

Very low–carbohydrate/high-fat (ketogenic) diet  

Ketogenic diets generally follow a VLCD with the carbohydrate portion set at 5% to 10% of total caloric intake (generally < 30 g/d) and the rest of the calories taken up by protein (typically 1 g/kg/d) and fat (TABLE 1^7-10).¹² The fat content recommended is primarily polyunsaturated fat such as olive oil, while saturated fats such as butter and lard (animal fat) should be limited.

A recent meta-analysis by Choi et al¹² showed that in overweight or obese patients with type 2 diabetes, the average A1C reduction was 0.62% (95% CI, –0.89 to –0.35) in the ketogenic intervention group. Another meta-analysis showed an even more significant A1C reduction at 1.07% (95% CI, –1.37 to –0.78).¹³ Concerns have been raised about the ketogenic diet, particularly as it relates to lipid metabolism and cholesterol levels; however, in the 2 referenced meta-analyses, the total cholesterol and triglyceride levels actually declined in the ketogenic intervention groups with minimal effect on LDL-C.^12,13 This may alleviate some of the concerns of lipid management with this diet.

Plant-based diet  

Popularized by Dr. T. Colin Campbell, a plant-based diet refers to a low-fat, high-fiber, whole-foods diet (whole fruits, vegetables, and naturally occurring carbohydrates, as opposed to processed foods). Examples of this type of diet include the popular vegan diet, which restricts all animal-derived products, and the vegetarian diet, which is generally limited to foods in the plant category with some addition of animal products, such as milk and cheese. Other variations of these diets exist and include other sources of protein (eg, chicken, eggs, or fish) (TABLE 1^7-10).

Continue to: A review by...

A review by Salas-Salvadó et al¹⁴ showed that a vegan diet yields an average A1C reduction of 0.41% (95% CI, –0.58 to –0.23).Several meta-analyses report similar effects on A1C with vegetarian and vegan eating patterns.^6,15,16 The ADA review notes that weight loss was more significant in the vegan group and concluded that this diet should be studied further while controlling for weight loss.⁶

Mediterranean  diet

The Mediterranean diet emphasizes vegetables, whole grains, fruits, lean meats, nuts, and olive oil. The benefits of the Mediterranean diet are well known and, as a result, the diet is recommended by organizations including the American Heart Association as part of a strategy to reduce cardiovascular risk (TABLE 1^7-10).

Mediterranean diet interventions have generally shown mixed effects on A1C reduction, weight management, and lipid control in type 2 diabetes. ⁶ The PREDIMED trial is the largest and longest randomized controlled trial to date comparing the Mediterranean diet to a low-fat diet. ¹⁷ This trial has reliably shown a reduced risk for type 2 diabetes and a trend to reduced A1C. ¹⁷ A reduction in the need for glucose-lowering medications was demonstrated in a subgroup analysis of the intervention group (adjusted hazard ratio = 0.78; 95% CI, 0.62-0.98). ¹⁸ Also, the Mediterranean diet has shown a significant reduction in the incidence of cardiovascular disease in patients with type 2 diabetes. ⁶

Physical activity and exercise

What do current guidelines recommend?

For most adults with type 2 diabetes, current guidelines by the ADA and by the National Institute of Diabetes and Digestive and Kidney Diseases recommend at least 150 minutes of moderate-to-vigorous intensity exercise every week spread out over at least 3 days, with no more than 2 consecutive days without exercise; and resistance training at least 2 other days per week which should balance all major muscle groups (TABLE 2^19-21). The benefits of exercise for type 2 diabetes have been well reviewed: positive effects on glucose control, insulin sensitivity, cardiovascular disease, lipid profiles, skeletal muscle metabolism, and solid-organ functioning.^19,22,23

Grace et al²⁴ showed in a meta-analysis that moderate aerobic exercise reduced A1C by 0.69% (95% CI, –1.09 to –0.3) at 13 weeks, and a Cochrane review showed an average A1C reduction of 0.6% with moderate-­intensity exercise.²⁵ Borror et al²⁶ demonstrated in a systematic review that postprandial moderate-intensity aerobic exercise starting 1 hour after meals results in a reduced 24-hour prevalence of hyperglycemia (33.5% reduction vs control). A meta-analysis in China showed an average A1C reduction of 0.68% for patients performing a Tai Chi physical activity intervention.²⁷

Continue to: Consider high-intensity interval training

Multiple randomized controlled trials highlight the benefits of high-intensity interval training (HIIT) (TABLE 2^19-21) compared with moderate-intensity continuous training (MICT) on improving A1C. A meta-analysis showed a weighted mean difference in A1C of 0.23% (95% CI, –0.43 to –0.02%).²⁸ Also, a patient could spend less time performing HIIT as opposed to MICT to achieve the same benefits. For example, a patient typically performing 30 minutes of MICT may only need to perform 15 minutes of HIIT,a time-saving option for patients.^20,22

Interrupt sedentary behavior

Risk for incident type 2 diabetes increases when someone is sedentary for more than 6 to 8 hours daily or watches TV for 3 to 4 hours (relative risk [RR] = 1.12).²⁹ Recommendations for interrupting a sedentary lifestyle include standing from a seated position at least every 30 minutes and engaging in a light activity during the break interval for at least 3 minutes.¹⁹ Most studies have reliably shown that interrupting sedentary behavior reduces postprandial and 24-hour average blood glucose levels.¹⁹ Interrupted sitting/sedentary behavior has also been shown to reduce resting blood pressure in patients with type 2 diabetes.³⁰

Other important lifestyle factors

Encourage 7 to 8 hours of sleep

There is a U-shaped association between glycemic control and sleep quantity based on a meta-analysis by Lee et al ³¹ that showed a 0.23% increase in A1C in patients with insufficient sleep (< 4.5-6 hours/night) and a 0.13% increase in patients with ≥ 8 hours of sleep per night. Patients should be encouraged to obtain 7 to 8 hours of sleep per night to help maximize their diabetes control.  

Address stress reduction

Although evidence for stress reduction interventions on glycemic control is mixed, there does seem to be a benefit in diminishing emotional distress in patients with diabetes. A systematic review by Noordali et al³² demonstrated that patients who received mindfulness-based interventions had improvements in stress, anxiety, and depression symptoms which resulted in improved quality of life. These psychological benefits may subsequently lead to positive behavioral changes.

Assist patients with smoking cessation 

A large meta-analysis showed that active smoking increases the risk of cardiovascular events in patients with type 2 diabetes (RR = 1.44; 95% CI, 1.34-1.54).³³ Former smokers still have an increased risk (RR = 1.09; 95% CI, 1.05-1.13), but it is lower than that of current smokers, so patients should be encouraged to quit smoking.^3,33

Continue to: How can I get my patient to change?

How can I get my patient to change?

The AACE recommends using motivational interviewing, behavioral therapy consultation, and wearable feedback devices (eg, accelerometers/pedometers) to stimulate behavioral change in patients.³ Motivational interviewing is the principal counseling strategy and is supported by multiple studies showing the benefits of using this technique in a clinical encounter to induce behavioral changes.³⁴ In general, offer receptive patients intensive behavioral interventions and provide them with resources to accomplish their goals.³⁵ For example, a 7-step yearly intensive behavioral counseling intervention over 3 years showed significant improvements in activity of any intensity, reduced sedentary time, and led to favorable metabolic outcomes.³⁶ Wearable devices result in up to a 1 hour increase in physical activity per week for the wearers vs control, although there was no appreciable effect on A1C.³⁷

A meta-analysis showed that moderate aerobic exercise reduced A1C by 0.69% at 13 weeks.

One systematic review showed a 0.5% reduction in A1C (95% CI, –0.65 to –0.34) by focusing on environmental changes related to the diet, with the most effective intervention being full meal replacement for calorie control (ie, each meal was pre-made and provided to the patients based on macronutrient and caloric goals).³⁸ Additionally, diabetes self-management education includes coping strategies, problem solving, self-­advocacy, and health care system navigation, which have been shown to reduce A1C by an average of 0.6%.²¹ Patient resources are available for further assistance with lifestyle modifications (TABLE 3).

Can your patient achieve remission?

Emerging evidence suggests that patients may achieve remission from type 2 diabetes with intensive lifestyle interventions.³⁹ This is supported by the American College of Lifestyle Medicine.⁵ Although there is no consensus definition for remission, in general it is reasonable to presume remission if a patient achieves normo-glycemia (A1C < 5.7%) for at least 1 year without any medication therapy.⁵ These intensive lifestyle interventions would include a mostly plant-based diet with moderate calorie restriction, appropriate and sustained physical activity, adequate sleep, and stress-reduction techniques.⁵ One study found that 46% of patients in a weight-management program across multiple primary care clinics achieved remission at 12 months.⁴⁰ A meta-analysis showed that a low-carbohydrate diet induced remission at 6 months in 32% of patients (although the result was not controlled for weight loss as a possible confounding factor and an A1C cutoff of 6.5% was used).¹¹ Thus far, most studies have focused on short-term follow-up intervals, but evidence is emerging that with intensive lifestyle interventions the effects are sustained at the 2-year mark.⁴¹

The American Academy of Clinical Endocrinologists recommends using motivational interviewing and wearable feedback devices to stimulate behavioral change in patients.

This evidence could reframe our understanding of type 2 diabetes therapy and could change the conversations we have with patients regarding their treatment. Instead of focusing on an A1C goal that is adequate for control of type 2 diabetes, we would instead focus on achieving remission.

CORRESPONDENCE
Stephen McMullan, MD, Mayo Clinic College of Medicine and Science, 4500 San Pablo Road, Jacksonville, FL 32224; [email protected]

Type 2 diabetes has been increasing in incidence and prevalence over the past 20 years, with worldwide prevalence estimated at 6.28%.¹ The estimated cost of diagnosed diabetes in the United States was $327 billion in 2017; this included direct medical costs and reduced productivity.² Type 2 diabetes can be prevented in most patients, given that it is a metabolic derangement caused by a complicated interaction between a patient’s genetic predisposition and lifestyle. A consensus statement by the American Academy of Clinical Endocrinologists (AACE) and American College of Endocrinology indicates that the recommended lifestyle modifications for diabetes include medical nutrition therapy with healthy eating patterns, regular physical activity, adequate sleep, behavioral support/counseling, and smoking cessation.³ Evidence shows that adherence to these lifestyle changes alone yields a relative reduction in type 2 diabetes mortality of 57%.⁴

IMAGE: ©ALICIA BUELOW; PATIENT IMAGE © GETTY IMAGES

In the discussion that follows, we review the current guideline recommendations for dietary modifications and physical activity and summarize their effectiveness in the treatment of type 2 diabetes. We also describe practical clinical strategies to promote change in patient behavior, and examine current literature supporting intensive lifestyle changes that, if achieved, may induce disease remission.⁵

Dietary strategies

Low, or very low, carbohydrate diet  

Carbohydrates can affect blood glucose levels in varying degrees depending on their intrinsic properties such as fiber content, sugars, and starches . ⁶ According to the American Diabetes Association’s (ADA) 2019 consensus report, ⁶ the carbohydrate quality that generally should be recommended is high in fiber, vitamins, and minerals, and low in added sugars, fats, and sodium (processed carbohydrates) ( TABLE 1 ^7-10 ). A low-carbohydrate diet (LCD) typically has a carbohydrate content < 130 g/d or < 26% of a 2000 kcal/d diet. ¹¹ A very low–carbohydrate diet (VLCD) is 20-50 g/d or < 10% of the 2000 kcal/day diet. ¹¹

Adherence to lifestyle changes alone yields a relative reduction in type 2 diabetes mortality of 57%.

In a meta-analysis by Goldenberg et al¹¹, the LCD was shown to reduce A1C by 0.47% at 6 months (95% CI, –0.6 to –0.34) and by 0.23% at 12 months when compared with control diets. A review of multiple meta-­analyses also showed a significant reduction in A1C especially with VLCD patterns; however, the results waned at the 12-month follow-up.⁵ In addition, confounding factors were seen when comparing adherence between LCD and VLCD, with patients in the latter group having larger problems with adherence, which decreased the benefit seen in the overall group comparison.¹¹

Very low–carbohydrate/high-fat (ketogenic) diet  

Ketogenic diets generally follow a VLCD with the carbohydrate portion set at 5% to 10% of total caloric intake (generally < 30 g/d) and the rest of the calories taken up by protein (typically 1 g/kg/d) and fat (TABLE 1^7-10).¹² The fat content recommended is primarily polyunsaturated fat such as olive oil, while saturated fats such as butter and lard (animal fat) should be limited.

A recent meta-analysis by Choi et al¹² showed that in overweight or obese patients with type 2 diabetes, the average A1C reduction was 0.62% (95% CI, –0.89 to –0.35) in the ketogenic intervention group. Another meta-analysis showed an even more significant A1C reduction at 1.07% (95% CI, –1.37 to –0.78).¹³ Concerns have been raised about the ketogenic diet, particularly as it relates to lipid metabolism and cholesterol levels; however, in the 2 referenced meta-analyses, the total cholesterol and triglyceride levels actually declined in the ketogenic intervention groups with minimal effect on LDL-C.^12,13 This may alleviate some of the concerns of lipid management with this diet.

Plant-based diet  

Popularized by Dr. T. Colin Campbell, a plant-based diet refers to a low-fat, high-fiber, whole-foods diet (whole fruits, vegetables, and naturally occurring carbohydrates, as opposed to processed foods). Examples of this type of diet include the popular vegan diet, which restricts all animal-derived products, and the vegetarian diet, which is generally limited to foods in the plant category with some addition of animal products, such as milk and cheese. Other variations of these diets exist and include other sources of protein (eg, chicken, eggs, or fish) (TABLE 1^7-10).

Continue to: A review by...

A review by Salas-Salvadó et al¹⁴ showed that a vegan diet yields an average A1C reduction of 0.41% (95% CI, –0.58 to –0.23).Several meta-analyses report similar effects on A1C with vegetarian and vegan eating patterns.^6,15,16 The ADA review notes that weight loss was more significant in the vegan group and concluded that this diet should be studied further while controlling for weight loss.⁶

Mediterranean  diet

The Mediterranean diet emphasizes vegetables, whole grains, fruits, lean meats, nuts, and olive oil. The benefits of the Mediterranean diet are well known and, as a result, the diet is recommended by organizations including the American Heart Association as part of a strategy to reduce cardiovascular risk (TABLE 1^7-10).

Mediterranean diet interventions have generally shown mixed effects on A1C reduction, weight management, and lipid control in type 2 diabetes. ⁶ The PREDIMED trial is the largest and longest randomized controlled trial to date comparing the Mediterranean diet to a low-fat diet. ¹⁷ This trial has reliably shown a reduced risk for type 2 diabetes and a trend to reduced A1C. ¹⁷ A reduction in the need for glucose-lowering medications was demonstrated in a subgroup analysis of the intervention group (adjusted hazard ratio = 0.78; 95% CI, 0.62-0.98). ¹⁸ Also, the Mediterranean diet has shown a significant reduction in the incidence of cardiovascular disease in patients with type 2 diabetes. ⁶

Physical activity and exercise

What do current guidelines recommend?

For most adults with type 2 diabetes, current guidelines by the ADA and by the National Institute of Diabetes and Digestive and Kidney Diseases recommend at least 150 minutes of moderate-to-vigorous intensity exercise every week spread out over at least 3 days, with no more than 2 consecutive days without exercise; and resistance training at least 2 other days per week which should balance all major muscle groups (TABLE 2^19-21). The benefits of exercise for type 2 diabetes have been well reviewed: positive effects on glucose control, insulin sensitivity, cardiovascular disease, lipid profiles, skeletal muscle metabolism, and solid-organ functioning.^19,22,23

Grace et al²⁴ showed in a meta-analysis that moderate aerobic exercise reduced A1C by 0.69% (95% CI, –1.09 to –0.3) at 13 weeks, and a Cochrane review showed an average A1C reduction of 0.6% with moderate-­intensity exercise.²⁵ Borror et al²⁶ demonstrated in a systematic review that postprandial moderate-intensity aerobic exercise starting 1 hour after meals results in a reduced 24-hour prevalence of hyperglycemia (33.5% reduction vs control). A meta-analysis in China showed an average A1C reduction of 0.68% for patients performing a Tai Chi physical activity intervention.²⁷

Continue to: Consider high-intensity interval training

Multiple randomized controlled trials highlight the benefits of high-intensity interval training (HIIT) (TABLE 2^19-21) compared with moderate-intensity continuous training (MICT) on improving A1C. A meta-analysis showed a weighted mean difference in A1C of 0.23% (95% CI, –0.43 to –0.02%).²⁸ Also, a patient could spend less time performing HIIT as opposed to MICT to achieve the same benefits. For example, a patient typically performing 30 minutes of MICT may only need to perform 15 minutes of HIIT,a time-saving option for patients.^20,22

Interrupt sedentary behavior

Risk for incident type 2 diabetes increases when someone is sedentary for more than 6 to 8 hours daily or watches TV for 3 to 4 hours (relative risk [RR] = 1.12).²⁹ Recommendations for interrupting a sedentary lifestyle include standing from a seated position at least every 30 minutes and engaging in a light activity during the break interval for at least 3 minutes.¹⁹ Most studies have reliably shown that interrupting sedentary behavior reduces postprandial and 24-hour average blood glucose levels.¹⁹ Interrupted sitting/sedentary behavior has also been shown to reduce resting blood pressure in patients with type 2 diabetes.³⁰

Other important lifestyle factors

Encourage 7 to 8 hours of sleep

There is a U-shaped association between glycemic control and sleep quantity based on a meta-analysis by Lee et al ³¹ that showed a 0.23% increase in A1C in patients with insufficient sleep (< 4.5-6 hours/night) and a 0.13% increase in patients with ≥ 8 hours of sleep per night. Patients should be encouraged to obtain 7 to 8 hours of sleep per night to help maximize their diabetes control.  

Address stress reduction

Although evidence for stress reduction interventions on glycemic control is mixed, there does seem to be a benefit in diminishing emotional distress in patients with diabetes. A systematic review by Noordali et al³² demonstrated that patients who received mindfulness-based interventions had improvements in stress, anxiety, and depression symptoms which resulted in improved quality of life. These psychological benefits may subsequently lead to positive behavioral changes.

Assist patients with smoking cessation 

A large meta-analysis showed that active smoking increases the risk of cardiovascular events in patients with type 2 diabetes (RR = 1.44; 95% CI, 1.34-1.54).³³ Former smokers still have an increased risk (RR = 1.09; 95% CI, 1.05-1.13), but it is lower than that of current smokers, so patients should be encouraged to quit smoking.^3,33

Continue to: How can I get my patient to change?

How can I get my patient to change?

The AACE recommends using motivational interviewing, behavioral therapy consultation, and wearable feedback devices (eg, accelerometers/pedometers) to stimulate behavioral change in patients.³ Motivational interviewing is the principal counseling strategy and is supported by multiple studies showing the benefits of using this technique in a clinical encounter to induce behavioral changes.³⁴ In general, offer receptive patients intensive behavioral interventions and provide them with resources to accomplish their goals.³⁵ For example, a 7-step yearly intensive behavioral counseling intervention over 3 years showed significant improvements in activity of any intensity, reduced sedentary time, and led to favorable metabolic outcomes.³⁶ Wearable devices result in up to a 1 hour increase in physical activity per week for the wearers vs control, although there was no appreciable effect on A1C.³⁷

A meta-analysis showed that moderate aerobic exercise reduced A1C by 0.69% at 13 weeks.

One systematic review showed a 0.5% reduction in A1C (95% CI, –0.65 to –0.34) by focusing on environmental changes related to the diet, with the most effective intervention being full meal replacement for calorie control (ie, each meal was pre-made and provided to the patients based on macronutrient and caloric goals).³⁸ Additionally, diabetes self-management education includes coping strategies, problem solving, self-­advocacy, and health care system navigation, which have been shown to reduce A1C by an average of 0.6%.²¹ Patient resources are available for further assistance with lifestyle modifications (TABLE 3).

Can your patient achieve remission?

Emerging evidence suggests that patients may achieve remission from type 2 diabetes with intensive lifestyle interventions.³⁹ This is supported by the American College of Lifestyle Medicine.⁵ Although there is no consensus definition for remission, in general it is reasonable to presume remission if a patient achieves normo-glycemia (A1C < 5.7%) for at least 1 year without any medication therapy.⁵ These intensive lifestyle interventions would include a mostly plant-based diet with moderate calorie restriction, appropriate and sustained physical activity, adequate sleep, and stress-reduction techniques.⁵ One study found that 46% of patients in a weight-management program across multiple primary care clinics achieved remission at 12 months.⁴⁰ A meta-analysis showed that a low-carbohydrate diet induced remission at 6 months in 32% of patients (although the result was not controlled for weight loss as a possible confounding factor and an A1C cutoff of 6.5% was used).¹¹ Thus far, most studies have focused on short-term follow-up intervals, but evidence is emerging that with intensive lifestyle interventions the effects are sustained at the 2-year mark.⁴¹

The American Academy of Clinical Endocrinologists recommends using motivational interviewing and wearable feedback devices to stimulate behavioral change in patients.

This evidence could reframe our understanding of type 2 diabetes therapy and could change the conversations we have with patients regarding their treatment. Instead of focusing on an A1C goal that is adequate for control of type 2 diabetes, we would instead focus on achieving remission.

CORRESPONDENCE
Stephen McMullan, MD, Mayo Clinic College of Medicine and Science, 4500 San Pablo Road, Jacksonville, FL 32224; [email protected]

Type 2 diabetes has been increasing in incidence and prevalence over the past 20 years, with worldwide prevalence estimated at 6.28%.¹ The estimated cost of diagnosed diabetes in the United States was $327 billion in 2017; this included direct medical costs and reduced productivity.² Type 2 diabetes can be prevented in most patients, given that it is a metabolic derangement caused by a complicated interaction between a patient’s genetic predisposition and lifestyle. A consensus statement by the American Academy of Clinical Endocrinologists (AACE) and American College of Endocrinology indicates that the recommended lifestyle modifications for diabetes include medical nutrition therapy with healthy eating patterns, regular physical activity, adequate sleep, behavioral support/counseling, and smoking cessation.³ Evidence shows that adherence to these lifestyle changes alone yields a relative reduction in type 2 diabetes mortality of 57%.⁴

IMAGE: ©ALICIA BUELOW; PATIENT IMAGE © GETTY IMAGES

In the discussion that follows, we review the current guideline recommendations for dietary modifications and physical activity and summarize their effectiveness in the treatment of type 2 diabetes. We also describe practical clinical strategies to promote change in patient behavior, and examine current literature supporting intensive lifestyle changes that, if achieved, may induce disease remission.⁵

Dietary strategies

Low, or very low, carbohydrate diet  

Carbohydrates can affect blood glucose levels in varying degrees depending on their intrinsic properties such as fiber content, sugars, and starches . ⁶ According to the American Diabetes Association’s (ADA) 2019 consensus report, ⁶ the carbohydrate quality that generally should be recommended is high in fiber, vitamins, and minerals, and low in added sugars, fats, and sodium (processed carbohydrates) ( TABLE 1 ^7-10 ). A low-carbohydrate diet (LCD) typically has a carbohydrate content < 130 g/d or < 26% of a 2000 kcal/d diet. ¹¹ A very low–carbohydrate diet (VLCD) is 20-50 g/d or < 10% of the 2000 kcal/day diet. ¹¹

Adherence to lifestyle changes alone yields a relative reduction in type 2 diabetes mortality of 57%.

In a meta-analysis by Goldenberg et al¹¹, the LCD was shown to reduce A1C by 0.47% at 6 months (95% CI, –0.6 to –0.34) and by 0.23% at 12 months when compared with control diets. A review of multiple meta-­analyses also showed a significant reduction in A1C especially with VLCD patterns; however, the results waned at the 12-month follow-up.⁵ In addition, confounding factors were seen when comparing adherence between LCD and VLCD, with patients in the latter group having larger problems with adherence, which decreased the benefit seen in the overall group comparison.¹¹

Very low–carbohydrate/high-fat (ketogenic) diet  

Ketogenic diets generally follow a VLCD with the carbohydrate portion set at 5% to 10% of total caloric intake (generally < 30 g/d) and the rest of the calories taken up by protein (typically 1 g/kg/d) and fat (TABLE 1^7-10).¹² The fat content recommended is primarily polyunsaturated fat such as olive oil, while saturated fats such as butter and lard (animal fat) should be limited.

A recent meta-analysis by Choi et al¹² showed that in overweight or obese patients with type 2 diabetes, the average A1C reduction was 0.62% (95% CI, –0.89 to –0.35) in the ketogenic intervention group. Another meta-analysis showed an even more significant A1C reduction at 1.07% (95% CI, –1.37 to –0.78).¹³ Concerns have been raised about the ketogenic diet, particularly as it relates to lipid metabolism and cholesterol levels; however, in the 2 referenced meta-analyses, the total cholesterol and triglyceride levels actually declined in the ketogenic intervention groups with minimal effect on LDL-C.^12,13 This may alleviate some of the concerns of lipid management with this diet.

Plant-based diet  

Popularized by Dr. T. Colin Campbell, a plant-based diet refers to a low-fat, high-fiber, whole-foods diet (whole fruits, vegetables, and naturally occurring carbohydrates, as opposed to processed foods). Examples of this type of diet include the popular vegan diet, which restricts all animal-derived products, and the vegetarian diet, which is generally limited to foods in the plant category with some addition of animal products, such as milk and cheese. Other variations of these diets exist and include other sources of protein (eg, chicken, eggs, or fish) (TABLE 1^7-10).

Continue to: A review by...

A review by Salas-Salvadó et al¹⁴ showed that a vegan diet yields an average A1C reduction of 0.41% (95% CI, –0.58 to –0.23).Several meta-analyses report similar effects on A1C with vegetarian and vegan eating patterns.^6,15,16 The ADA review notes that weight loss was more significant in the vegan group and concluded that this diet should be studied further while controlling for weight loss.⁶

Mediterranean  diet

The Mediterranean diet emphasizes vegetables, whole grains, fruits, lean meats, nuts, and olive oil. The benefits of the Mediterranean diet are well known and, as a result, the diet is recommended by organizations including the American Heart Association as part of a strategy to reduce cardiovascular risk (TABLE 1^7-10).

Mediterranean diet interventions have generally shown mixed effects on A1C reduction, weight management, and lipid control in type 2 diabetes. ⁶ The PREDIMED trial is the largest and longest randomized controlled trial to date comparing the Mediterranean diet to a low-fat diet. ¹⁷ This trial has reliably shown a reduced risk for type 2 diabetes and a trend to reduced A1C. ¹⁷ A reduction in the need for glucose-lowering medications was demonstrated in a subgroup analysis of the intervention group (adjusted hazard ratio = 0.78; 95% CI, 0.62-0.98). ¹⁸ Also, the Mediterranean diet has shown a significant reduction in the incidence of cardiovascular disease in patients with type 2 diabetes. ⁶

Physical activity and exercise

What do current guidelines recommend?

For most adults with type 2 diabetes, current guidelines by the ADA and by the National Institute of Diabetes and Digestive and Kidney Diseases recommend at least 150 minutes of moderate-to-vigorous intensity exercise every week spread out over at least 3 days, with no more than 2 consecutive days without exercise; and resistance training at least 2 other days per week which should balance all major muscle groups (TABLE 2^19-21). The benefits of exercise for type 2 diabetes have been well reviewed: positive effects on glucose control, insulin sensitivity, cardiovascular disease, lipid profiles, skeletal muscle metabolism, and solid-organ functioning.^19,22,23

Grace et al²⁴ showed in a meta-analysis that moderate aerobic exercise reduced A1C by 0.69% (95% CI, –1.09 to –0.3) at 13 weeks, and a Cochrane review showed an average A1C reduction of 0.6% with moderate-­intensity exercise.²⁵ Borror et al²⁶ demonstrated in a systematic review that postprandial moderate-intensity aerobic exercise starting 1 hour after meals results in a reduced 24-hour prevalence of hyperglycemia (33.5% reduction vs control). A meta-analysis in China showed an average A1C reduction of 0.68% for patients performing a Tai Chi physical activity intervention.²⁷

Continue to: Consider high-intensity interval training

Multiple randomized controlled trials highlight the benefits of high-intensity interval training (HIIT) (TABLE 2^19-21) compared with moderate-intensity continuous training (MICT) on improving A1C. A meta-analysis showed a weighted mean difference in A1C of 0.23% (95% CI, –0.43 to –0.02%).²⁸ Also, a patient could spend less time performing HIIT as opposed to MICT to achieve the same benefits. For example, a patient typically performing 30 minutes of MICT may only need to perform 15 minutes of HIIT,a time-saving option for patients.^20,22

Interrupt sedentary behavior

Risk for incident type 2 diabetes increases when someone is sedentary for more than 6 to 8 hours daily or watches TV for 3 to 4 hours (relative risk [RR] = 1.12).²⁹ Recommendations for interrupting a sedentary lifestyle include standing from a seated position at least every 30 minutes and engaging in a light activity during the break interval for at least 3 minutes.¹⁹ Most studies have reliably shown that interrupting sedentary behavior reduces postprandial and 24-hour average blood glucose levels.¹⁹ Interrupted sitting/sedentary behavior has also been shown to reduce resting blood pressure in patients with type 2 diabetes.³⁰

Other important lifestyle factors

Encourage 7 to 8 hours of sleep

There is a U-shaped association between glycemic control and sleep quantity based on a meta-analysis by Lee et al ³¹ that showed a 0.23% increase in A1C in patients with insufficient sleep (< 4.5-6 hours/night) and a 0.13% increase in patients with ≥ 8 hours of sleep per night. Patients should be encouraged to obtain 7 to 8 hours of sleep per night to help maximize their diabetes control.  

Address stress reduction

Although evidence for stress reduction interventions on glycemic control is mixed, there does seem to be a benefit in diminishing emotional distress in patients with diabetes. A systematic review by Noordali et al³² demonstrated that patients who received mindfulness-based interventions had improvements in stress, anxiety, and depression symptoms which resulted in improved quality of life. These psychological benefits may subsequently lead to positive behavioral changes.

Assist patients with smoking cessation 

A large meta-analysis showed that active smoking increases the risk of cardiovascular events in patients with type 2 diabetes (RR = 1.44; 95% CI, 1.34-1.54).³³ Former smokers still have an increased risk (RR = 1.09; 95% CI, 1.05-1.13), but it is lower than that of current smokers, so patients should be encouraged to quit smoking.^3,33

Continue to: How can I get my patient to change?

How can I get my patient to change?

The AACE recommends using motivational interviewing, behavioral therapy consultation, and wearable feedback devices (eg, accelerometers/pedometers) to stimulate behavioral change in patients.³ Motivational interviewing is the principal counseling strategy and is supported by multiple studies showing the benefits of using this technique in a clinical encounter to induce behavioral changes.³⁴ In general, offer receptive patients intensive behavioral interventions and provide them with resources to accomplish their goals.³⁵ For example, a 7-step yearly intensive behavioral counseling intervention over 3 years showed significant improvements in activity of any intensity, reduced sedentary time, and led to favorable metabolic outcomes.³⁶ Wearable devices result in up to a 1 hour increase in physical activity per week for the wearers vs control, although there was no appreciable effect on A1C.³⁷

A meta-analysis showed that moderate aerobic exercise reduced A1C by 0.69% at 13 weeks.

One systematic review showed a 0.5% reduction in A1C (95% CI, –0.65 to –0.34) by focusing on environmental changes related to the diet, with the most effective intervention being full meal replacement for calorie control (ie, each meal was pre-made and provided to the patients based on macronutrient and caloric goals).³⁸ Additionally, diabetes self-management education includes coping strategies, problem solving, self-­advocacy, and health care system navigation, which have been shown to reduce A1C by an average of 0.6%.²¹ Patient resources are available for further assistance with lifestyle modifications (TABLE 3).

Can your patient achieve remission?

Emerging evidence suggests that patients may achieve remission from type 2 diabetes with intensive lifestyle interventions.³⁹ This is supported by the American College of Lifestyle Medicine.⁵ Although there is no consensus definition for remission, in general it is reasonable to presume remission if a patient achieves normo-glycemia (A1C < 5.7%) for at least 1 year without any medication therapy.⁵ These intensive lifestyle interventions would include a mostly plant-based diet with moderate calorie restriction, appropriate and sustained physical activity, adequate sleep, and stress-reduction techniques.⁵ One study found that 46% of patients in a weight-management program across multiple primary care clinics achieved remission at 12 months.⁴⁰ A meta-analysis showed that a low-carbohydrate diet induced remission at 6 months in 32% of patients (although the result was not controlled for weight loss as a possible confounding factor and an A1C cutoff of 6.5% was used).¹¹ Thus far, most studies have focused on short-term follow-up intervals, but evidence is emerging that with intensive lifestyle interventions the effects are sustained at the 2-year mark.⁴¹

The American Academy of Clinical Endocrinologists recommends using motivational interviewing and wearable feedback devices to stimulate behavioral change in patients.

This evidence could reframe our understanding of type 2 diabetes therapy and could change the conversations we have with patients regarding their treatment. Instead of focusing on an A1C goal that is adequate for control of type 2 diabetes, we would instead focus on achieving remission.

CORRESPONDENCE
Stephen McMullan, MD, Mayo Clinic College of Medicine and Science, 4500 San Pablo Road, Jacksonville, FL 32224; [email protected]

THE COMPARISON

A Areas of alopecia with erythema and scale in a young Black boy with tinea capitis. He also had an enlarged posterior cervical lymph node (arrow) from this fungal infection.

B White patches of scale from tinea capitis in a young Black boy with no obvious hair loss; however, a potassium hydroxide preparation from the scale was positive for fungus.

C A subtle area of tinea capitis on the scalp of a Latina girl showed comma hairs.

Tinea capitis is a common dermatophyte infection of the scalp in school-aged children. The infection is spread by close contact with infected people or with their personal items, including combs, brushes, pillowcases, and hats, as well as animals. It is uncommon in adults.

Epidemiology

Tinea capitis is the most common fungal infection among school-aged children worldwide.¹ In a US-based study of more than 10,000 school-aged children, the prevalence of tinea capitis ranged from 0% to 19.4%, with Black children having the highest rates of infection at 12.9%.² However, people of all races and ages may develop tinea capitis.³

Tinea capitis most commonly is caused by Trichophyton tonsurans and Microsporum canis. Dermatophyte scalp infections caused by T tonsurans produce fungal spores that may occur within the hair shaft (endothrix) or with fungal elements external to the hair shaft (exothrix) caused by M canis. M canis usually fluoresces an apple green color on Wood lamp examination because of the location of the spores.

Key clinical features

Tinea capitis has a variety of clinical presentations:

• broken hairs that appear as black dots on the scalp
• diffuse scale mimicking seborrheic dermatitis
• well-demarcated annular plaques
• exudate and tenderness caused by inflammation
• scalp pruritus
• occipital scalp lymphadenopathy.

Worth noting

Tinea capitis impacts all patient groups, not just Black patients. In the United States, Black and Hispanic children are most commonly affected.⁴ Due to a tendency to have dry hair and hair breakage, those with more tightly coiled, textured hair may routinely apply oil and/or grease to the scalp. However, the application of heavy emollients, oils, and grease to camouflage scale contributes to false-negative fungal cultures of the scalp if applied within 1 week of the fungal culture, which may delay diagnosis. If tinea capitis is suspected, occipital lymphadenopathy on physical examination should prompt treatment for tinea capitis, even without a fungal culture.⁵

Health disparity highlight

A risk factor for tinea capitis is crowded living environments. Some families may live in crowded environments due to economic and housing disparities. This close contact increases the risk for conditions such as tinea capitis.⁶ Treatment delays may occur due to some cultural practices of applying oils and grease to the hair and scalp, camouflaging the clinical signs of tinea capitis.

THE COMPARISON

A Areas of alopecia with erythema and scale in a young Black boy with tinea capitis. He also had an enlarged posterior cervical lymph node (arrow) from this fungal infection.

B White patches of scale from tinea capitis in a young Black boy with no obvious hair loss; however, a potassium hydroxide preparation from the scale was positive for fungus.

C A subtle area of tinea capitis on the scalp of a Latina girl showed comma hairs.

Tinea capitis is a common dermatophyte infection of the scalp in school-aged children. The infection is spread by close contact with infected people or with their personal items, including combs, brushes, pillowcases, and hats, as well as animals. It is uncommon in adults.

Epidemiology

Tinea capitis is the most common fungal infection among school-aged children worldwide.¹ In a US-based study of more than 10,000 school-aged children, the prevalence of tinea capitis ranged from 0% to 19.4%, with Black children having the highest rates of infection at 12.9%.² However, people of all races and ages may develop tinea capitis.³

Tinea capitis most commonly is caused by Trichophyton tonsurans and Microsporum canis. Dermatophyte scalp infections caused by T tonsurans produce fungal spores that may occur within the hair shaft (endothrix) or with fungal elements external to the hair shaft (exothrix) caused by M canis. M canis usually fluoresces an apple green color on Wood lamp examination because of the location of the spores.

Key clinical features

Tinea capitis has a variety of clinical presentations:

• broken hairs that appear as black dots on the scalp
• diffuse scale mimicking seborrheic dermatitis
• well-demarcated annular plaques
• exudate and tenderness caused by inflammation
• scalp pruritus
• occipital scalp lymphadenopathy.

Worth noting

Tinea capitis impacts all patient groups, not just Black patients. In the United States, Black and Hispanic children are most commonly affected.⁴ Due to a tendency to have dry hair and hair breakage, those with more tightly coiled, textured hair may routinely apply oil and/or grease to the scalp. However, the application of heavy emollients, oils, and grease to camouflage scale contributes to false-negative fungal cultures of the scalp if applied within 1 week of the fungal culture, which may delay diagnosis. If tinea capitis is suspected, occipital lymphadenopathy on physical examination should prompt treatment for tinea capitis, even without a fungal culture.⁵

Health disparity highlight

A risk factor for tinea capitis is crowded living environments. Some families may live in crowded environments due to economic and housing disparities. This close contact increases the risk for conditions such as tinea capitis.⁶ Treatment delays may occur due to some cultural practices of applying oils and grease to the hair and scalp, camouflaging the clinical signs of tinea capitis.

THE COMPARISON

A Areas of alopecia with erythema and scale in a young Black boy with tinea capitis. He also had an enlarged posterior cervical lymph node (arrow) from this fungal infection.

B White patches of scale from tinea capitis in a young Black boy with no obvious hair loss; however, a potassium hydroxide preparation from the scale was positive for fungus.

C A subtle area of tinea capitis on the scalp of a Latina girl showed comma hairs.

Tinea capitis is a common dermatophyte infection of the scalp in school-aged children. The infection is spread by close contact with infected people or with their personal items, including combs, brushes, pillowcases, and hats, as well as animals. It is uncommon in adults.

Epidemiology

Tinea capitis is the most common fungal infection among school-aged children worldwide.¹ In a US-based study of more than 10,000 school-aged children, the prevalence of tinea capitis ranged from 0% to 19.4%, with Black children having the highest rates of infection at 12.9%.² However, people of all races and ages may develop tinea capitis.³

Tinea capitis most commonly is caused by Trichophyton tonsurans and Microsporum canis. Dermatophyte scalp infections caused by T tonsurans produce fungal spores that may occur within the hair shaft (endothrix) or with fungal elements external to the hair shaft (exothrix) caused by M canis. M canis usually fluoresces an apple green color on Wood lamp examination because of the location of the spores.

Key clinical features

Tinea capitis has a variety of clinical presentations:

• broken hairs that appear as black dots on the scalp
• diffuse scale mimicking seborrheic dermatitis
• well-demarcated annular plaques
• exudate and tenderness caused by inflammation
• scalp pruritus
• occipital scalp lymphadenopathy.

Worth noting

Tinea capitis impacts all patient groups, not just Black patients. In the United States, Black and Hispanic children are most commonly affected.⁴ Due to a tendency to have dry hair and hair breakage, those with more tightly coiled, textured hair may routinely apply oil and/or grease to the scalp. However, the application of heavy emollients, oils, and grease to camouflage scale contributes to false-negative fungal cultures of the scalp if applied within 1 week of the fungal culture, which may delay diagnosis. If tinea capitis is suspected, occipital lymphadenopathy on physical examination should prompt treatment for tinea capitis, even without a fungal culture.⁵

Health disparity highlight

A risk factor for tinea capitis is crowded living environments. Some families may live in crowded environments due to economic and housing disparities. This close contact increases the risk for conditions such as tinea capitis.⁶ Treatment delays may occur due to some cultural practices of applying oils and grease to the hair and scalp, camouflaging the clinical signs of tinea capitis.

Dermoscopy revealed a uniform, sharply demarcated, slightly scaly lesion on a background of occasional scale and solar-damaged skin. This appearance, paired with the absence of abnormal blood vessels or suspicious, irregular pigmentation, pointed to a diagnosis of benign lichenoid keratosis also known as lichenoid keratosis (LK) or lichen planus-like keratosis. (It’s worth noting that in some cases, a dermoscopic evaluation will reveal blue-grey dots rather than the uniform, velvety brown pigmentation that was seen here.)

LK is a benign reactive inflammatory lesion that usually manifests as a solitary lesion in middle age. LKs can be found on the trunk or lower extremities. As the alternative name “lichen planus-like keratosis” implies, the lesions can be purple, polygonal, raised, and have stria. The etiology is unknown but thought to be a reaction to a lentigo or another lesion, resulting in an inflammatory infiltrate.¹

If dermoscopic evaluation of the lesion is unclear, biopsy is warranted. Maor et al¹ reported the pathology results of 263 consecutive patients with a histologic diagnosis of LK. Of those cases, 47% were clinically thought to be basal cell carcinoma (BCC) and 18% were submitted with a diagnosis of seborrheic keratosis.¹ The high rate of concern for BCC and not listing a diagnosis of LK may have been the result of clinicians doing biopsies on the atypical lesions and clinically following the typical banal lesions.

At the patient’s request, he was given a written list of the diagnoses of his various skin lesions and advised that his LK was benign and did not require treatment. He was advised to continue coming in for serial skin examinations and report any concerning lesions in the interim.

‌

Image and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo.

Dermoscopy revealed a uniform, sharply demarcated, slightly scaly lesion on a background of occasional scale and solar-damaged skin. This appearance, paired with the absence of abnormal blood vessels or suspicious, irregular pigmentation, pointed to a diagnosis of benign lichenoid keratosis also known as lichenoid keratosis (LK) or lichen planus-like keratosis. (It’s worth noting that in some cases, a dermoscopic evaluation will reveal blue-grey dots rather than the uniform, velvety brown pigmentation that was seen here.)

LK is a benign reactive inflammatory lesion that usually manifests as a solitary lesion in middle age. LKs can be found on the trunk or lower extremities. As the alternative name “lichen planus-like keratosis” implies, the lesions can be purple, polygonal, raised, and have stria. The etiology is unknown but thought to be a reaction to a lentigo or another lesion, resulting in an inflammatory infiltrate.¹

If dermoscopic evaluation of the lesion is unclear, biopsy is warranted. Maor et al¹ reported the pathology results of 263 consecutive patients with a histologic diagnosis of LK. Of those cases, 47% were clinically thought to be basal cell carcinoma (BCC) and 18% were submitted with a diagnosis of seborrheic keratosis.¹ The high rate of concern for BCC and not listing a diagnosis of LK may have been the result of clinicians doing biopsies on the atypical lesions and clinically following the typical banal lesions.

At the patient’s request, he was given a written list of the diagnoses of his various skin lesions and advised that his LK was benign and did not require treatment. He was advised to continue coming in for serial skin examinations and report any concerning lesions in the interim.

‌

Image and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo.

Dermoscopy revealed a uniform, sharply demarcated, slightly scaly lesion on a background of occasional scale and solar-damaged skin. This appearance, paired with the absence of abnormal blood vessels or suspicious, irregular pigmentation, pointed to a diagnosis of benign lichenoid keratosis also known as lichenoid keratosis (LK) or lichen planus-like keratosis. (It’s worth noting that in some cases, a dermoscopic evaluation will reveal blue-grey dots rather than the uniform, velvety brown pigmentation that was seen here.)

LK is a benign reactive inflammatory lesion that usually manifests as a solitary lesion in middle age. LKs can be found on the trunk or lower extremities. As the alternative name “lichen planus-like keratosis” implies, the lesions can be purple, polygonal, raised, and have stria. The etiology is unknown but thought to be a reaction to a lentigo or another lesion, resulting in an inflammatory infiltrate.¹

If dermoscopic evaluation of the lesion is unclear, biopsy is warranted. Maor et al¹ reported the pathology results of 263 consecutive patients with a histologic diagnosis of LK. Of those cases, 47% were clinically thought to be basal cell carcinoma (BCC) and 18% were submitted with a diagnosis of seborrheic keratosis.¹ The high rate of concern for BCC and not listing a diagnosis of LK may have been the result of clinicians doing biopsies on the atypical lesions and clinically following the typical banal lesions.

At the patient’s request, he was given a written list of the diagnoses of his various skin lesions and advised that his LK was benign and did not require treatment. He was advised to continue coming in for serial skin examinations and report any concerning lesions in the interim.

‌

Image and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo.

THE COMPARISON

A Areas of alopecia with erythema and scale in a young Black boy with tinea capitis. He also had an enlarged posterior cervical lymph node (arrow) from this fungal infection.

B White patches of scale from tinea capitis in a young Black boy with no obvious hair loss; however, a potassium hydroxide preparation from the scale was positive for fungus.

C A subtle area of tinea capitis on the scalp of a Latina girl showed comma hairs.

Photographs courtesy of Richard P. Usatine, MD.

Tinea capitis is a common dermatophyte infection of the scalp in school-aged children. The infection is spread by close contact with infected people or with their personal items, including combs, brushes, pillowcases, and hats, as well as animals. It is uncommon in adults.

Epidemiology

Tinea capitis is the most common fungal infection among school-aged children worldwide.¹ In a US-based study of more than 10,000 school-aged children, the prevalence of tinea capitis ranged from 0% to 19.4%, with Black children having the highest rates of infection at 12.9%.² However, people of all races and ages may develop tinea capitis.³

Tinea capitis most commonly is caused by Trichophyton tonsurans and Microsporum canis. Dermatophyte scalp infections caused by T tonsurans produce fungal spores that may occur within the hair shaft (endothrix) or with fungal elements external to the hair shaft (exothrix) such as M canis. Microsporum canis usually fluoresces an apple green color on Wood lamp examination because of the location of the spores.

Key clinical features

Tinea capitis has a variety of clinical presentations: • broken hairs that appear as black dots on the scalp • diffuse scale mimicking seborrheic dermatitis • well-demarcated annular plaques • exudate and tenderness caused by inflammation • scalp pruritus • occipital scalp lymphadenopathy. Worth noting Tinea capitis impacts all patient groups, not just Black patients. In the United States, Black and Hispanic children are most commonly affected.4 Due to a tendency to have dry hair and hair breakage, those with more tightly coiled, textured hair may routinely apply oil and/or grease to the scalp; however, the application of heavy emollients, oils, and grease to camouflage scale contributes to falsenegative fungal cultures of the scalp if applied within 1 week of the fungal culture, which may delay diagnosis. If tinea capitis is suspected, occipital lymphadenopathy on physical examination should prompt treatment for tinea capitis, even without a fungal culture.5 Health disparity highlight A risk factor for tinea capitis is crowded living environments. Some families may live in crowded environments due to economic and housing disparities. This close contact increases the risk for conditions such as tinea capitis.6 Treatment delays may occur due to some cultural practices of applying oils and grease to the hair and scalp, camouflaging the clinical signs of tinea capitis.

THE COMPARISON

A Areas of alopecia with erythema and scale in a young Black boy with tinea capitis. He also had an enlarged posterior cervical lymph node (arrow) from this fungal infection.

B White patches of scale from tinea capitis in a young Black boy with no obvious hair loss; however, a potassium hydroxide preparation from the scale was positive for fungus.

C A subtle area of tinea capitis on the scalp of a Latina girl showed comma hairs.

Photographs courtesy of Richard P. Usatine, MD.

Tinea capitis is a common dermatophyte infection of the scalp in school-aged children. The infection is spread by close contact with infected people or with their personal items, including combs, brushes, pillowcases, and hats, as well as animals. It is uncommon in adults.

Epidemiology

Tinea capitis is the most common fungal infection among school-aged children worldwide.¹ In a US-based study of more than 10,000 school-aged children, the prevalence of tinea capitis ranged from 0% to 19.4%, with Black children having the highest rates of infection at 12.9%.² However, people of all races and ages may develop tinea capitis.³

Tinea capitis most commonly is caused by Trichophyton tonsurans and Microsporum canis. Dermatophyte scalp infections caused by T tonsurans produce fungal spores that may occur within the hair shaft (endothrix) or with fungal elements external to the hair shaft (exothrix) such as M canis. Microsporum canis usually fluoresces an apple green color on Wood lamp examination because of the location of the spores.

Key clinical features

Tinea capitis has a variety of clinical presentations: • broken hairs that appear as black dots on the scalp • diffuse scale mimicking seborrheic dermatitis • well-demarcated annular plaques • exudate and tenderness caused by inflammation • scalp pruritus • occipital scalp lymphadenopathy. Worth noting Tinea capitis impacts all patient groups, not just Black patients. In the United States, Black and Hispanic children are most commonly affected.4 Due to a tendency to have dry hair and hair breakage, those with more tightly coiled, textured hair may routinely apply oil and/or grease to the scalp; however, the application of heavy emollients, oils, and grease to camouflage scale contributes to falsenegative fungal cultures of the scalp if applied within 1 week of the fungal culture, which may delay diagnosis. If tinea capitis is suspected, occipital lymphadenopathy on physical examination should prompt treatment for tinea capitis, even without a fungal culture.5 Health disparity highlight A risk factor for tinea capitis is crowded living environments. Some families may live in crowded environments due to economic and housing disparities. This close contact increases the risk for conditions such as tinea capitis.6 Treatment delays may occur due to some cultural practices of applying oils and grease to the hair and scalp, camouflaging the clinical signs of tinea capitis.

THE COMPARISON

A Areas of alopecia with erythema and scale in a young Black boy with tinea capitis. He also had an enlarged posterior cervical lymph node (arrow) from this fungal infection.

B White patches of scale from tinea capitis in a young Black boy with no obvious hair loss; however, a potassium hydroxide preparation from the scale was positive for fungus.

C A subtle area of tinea capitis on the scalp of a Latina girl showed comma hairs.

Photographs courtesy of Richard P. Usatine, MD.

Tinea capitis is a common dermatophyte infection of the scalp in school-aged children. The infection is spread by close contact with infected people or with their personal items, including combs, brushes, pillowcases, and hats, as well as animals. It is uncommon in adults.

Epidemiology

Tinea capitis is the most common fungal infection among school-aged children worldwide.¹ In a US-based study of more than 10,000 school-aged children, the prevalence of tinea capitis ranged from 0% to 19.4%, with Black children having the highest rates of infection at 12.9%.² However, people of all races and ages may develop tinea capitis.³

Tinea capitis most commonly is caused by Trichophyton tonsurans and Microsporum canis. Dermatophyte scalp infections caused by T tonsurans produce fungal spores that may occur within the hair shaft (endothrix) or with fungal elements external to the hair shaft (exothrix) such as M canis. Microsporum canis usually fluoresces an apple green color on Wood lamp examination because of the location of the spores.

Key clinical features

Tinea capitis has a variety of clinical presentations: • broken hairs that appear as black dots on the scalp • diffuse scale mimicking seborrheic dermatitis • well-demarcated annular plaques • exudate and tenderness caused by inflammation • scalp pruritus • occipital scalp lymphadenopathy. Worth noting Tinea capitis impacts all patient groups, not just Black patients. In the United States, Black and Hispanic children are most commonly affected.4 Due to a tendency to have dry hair and hair breakage, those with more tightly coiled, textured hair may routinely apply oil and/or grease to the scalp; however, the application of heavy emollients, oils, and grease to camouflage scale contributes to falsenegative fungal cultures of the scalp if applied within 1 week of the fungal culture, which may delay diagnosis. If tinea capitis is suspected, occipital lymphadenopathy on physical examination should prompt treatment for tinea capitis, even without a fungal culture.5 Health disparity highlight A risk factor for tinea capitis is crowded living environments. Some families may live in crowded environments due to economic and housing disparities. This close contact increases the risk for conditions such as tinea capitis.6 Treatment delays may occur due to some cultural practices of applying oils and grease to the hair and scalp, camouflaging the clinical signs of tinea capitis.

SAN DIEGO—Before the pandemic, an estimated one-third of oncologists worldwide suffered a high level of burnout. Cancer physicians face many of the same risk factors as their colleagues—high workloads, lack of autonomy, and no support—along with the added pressure of working in a medical field where patients often die. Then COVID-19 hit, and the burnout crisis got even worse.

This tide can be reversed with a focus on best practices and resilience, a mental health researcher told cancer professionals at the September 2022 annual meeting of the Association of VA Hematology/Oncology. Assessments, long-term interventions, and communication are all key, said Fay J. Hlubocky, PhD, MA, a clinical health psychologist and ethicist at the University of Chicago.

Even simple actions like taking time for “mindful moments” and checking in with a colleague can make a difference, she said. But institutions must act, she said. “Long-term tailored strategies are incredibly important to promote well-being.”

Hlubocky, who led an American Society of Clinical Oncology committee on burnout prior to the pandemic, noted that statistics about burnout in American medicine and oncology specifically, are grim. In 2017, a systematic review and meta-analysis found that significant numbers of oncologists suffered from high burnout (32%), high psychiatric morbidity (27%), depression (at least 12%), and alcohol misuse (as many as 30%).

The pandemic piled on more stressors. In the second half of 2020, researchers interviewed 25 American oncologists in focus groups and found that their “underlying oncologist burnout exacerbated stressors associated with disruptions in care, education, research, financial practice health, and telemedicine. Many feared delays in cancer screening, diagnosis, and treatment [and] strongly considered working part-time or taking early retirement.”

As one participant put it, “everyone is seeing a lot of death and heartache and social isolation and anger that they’re not used to encountering and in very new and different ways.”

Major contributors to oncologist burnout, Hlubocky said, include moral distress, moral injury, and compassion fatigue. “Moral distress occurs when that individual believes he or she knows the right thing to do, but institutional constraints make it really difficult to do what is right,” Hlubocky said. “The individual is aware of the moral problem, acknowledges and takes moral responsibility, makes some moral judgments, but yet—as a result of these constraints — participates in perceived moral wrongdoing.”

Moral injury refers to the damage that can be caused by moral distress or by witnessing acts that violate morals, such as during military service. Compassion fatigue, meanwhile, is defined by the American Stress Institute as “a low level, chronic clouding of caring and concern for others in your life.”

What can be done? Hlubocky highlighted multiple interventions, such as adjustment of work patterns, cognitive behavioral therapy, and training in mindfulness, relaxation, and communication. One strategy is to adopt multiple in-person interventions simultaneously.

But first it’s crucial for administrators to understand the problem in a specific workplace: “You have to know what’s going on in your organization to intervene on it,” she said. “There are multiple tools that have been validated in other health care fields and can be used on a regular basis over time to measure burnout, satisfaction, and engagement.”

For individuals, other strategies include daily check-ins with colleagues to catch signs of stress, she said, as Toronto oncologists started doing amid the pandemic. The check-ins can include simple questions like: How are you doing? How are you feeling? Are you sleeping, eating and exercising? Do you need help?

As for resilience, Hlubocky said it must grow at the individual level. “We can't rely so much on the organization. We need to develop our personal resilience in order for professional resilience to flourish again, and we have to do a lot to protect ourselves. It’s about focusing on the strength of the individual—that empowerment to rise above adversity, that vitality, that engagement, that self-efficacy. It supports health and enhances coping, and it is the key element of physician and clinician well-being.”

Research into resilience offers guidance about how to achieve it, she said. A 2013 German study of 200 physicians found that the most resilient physicians change their attitudes and behaviors, take time off, set boundaries, spend time with family and friends, and ask colleagues for help. And they gained resilience, the study found, by getting older and becoming more experienced.

Hlubocky pointed to several useful resources for burned-out medical professionals, including mindfulness, cognitive behavioral therapy and breathing apps: She highlighted Breathe2Relax, Headspace, MoodGYM, Stress Gym, and guided audio files from the University of California at San Diego. And she said ASCO has resources on combatting burnout and promoting well-being.

Hlubocky has no relevant disclosures.

SAN DIEGO—Before the pandemic, an estimated one-third of oncologists worldwide suffered a high level of burnout. Cancer physicians face many of the same risk factors as their colleagues—high workloads, lack of autonomy, and no support—along with the added pressure of working in a medical field where patients often die. Then COVID-19 hit, and the burnout crisis got even worse.

This tide can be reversed with a focus on best practices and resilience, a mental health researcher told cancer professionals at the September 2022 annual meeting of the Association of VA Hematology/Oncology. Assessments, long-term interventions, and communication are all key, said Fay J. Hlubocky, PhD, MA, a clinical health psychologist and ethicist at the University of Chicago.

Even simple actions like taking time for “mindful moments” and checking in with a colleague can make a difference, she said. But institutions must act, she said. “Long-term tailored strategies are incredibly important to promote well-being.”

Hlubocky, who led an American Society of Clinical Oncology committee on burnout prior to the pandemic, noted that statistics about burnout in American medicine and oncology specifically, are grim. In 2017, a systematic review and meta-analysis found that significant numbers of oncologists suffered from high burnout (32%), high psychiatric morbidity (27%), depression (at least 12%), and alcohol misuse (as many as 30%).

The pandemic piled on more stressors. In the second half of 2020, researchers interviewed 25 American oncologists in focus groups and found that their “underlying oncologist burnout exacerbated stressors associated with disruptions in care, education, research, financial practice health, and telemedicine. Many feared delays in cancer screening, diagnosis, and treatment [and] strongly considered working part-time or taking early retirement.”

As one participant put it, “everyone is seeing a lot of death and heartache and social isolation and anger that they’re not used to encountering and in very new and different ways.”

Major contributors to oncologist burnout, Hlubocky said, include moral distress, moral injury, and compassion fatigue. “Moral distress occurs when that individual believes he or she knows the right thing to do, but institutional constraints make it really difficult to do what is right,” Hlubocky said. “The individual is aware of the moral problem, acknowledges and takes moral responsibility, makes some moral judgments, but yet—as a result of these constraints — participates in perceived moral wrongdoing.”

Moral injury refers to the damage that can be caused by moral distress or by witnessing acts that violate morals, such as during military service. Compassion fatigue, meanwhile, is defined by the American Stress Institute as “a low level, chronic clouding of caring and concern for others in your life.”

What can be done? Hlubocky highlighted multiple interventions, such as adjustment of work patterns, cognitive behavioral therapy, and training in mindfulness, relaxation, and communication. One strategy is to adopt multiple in-person interventions simultaneously.

But first it’s crucial for administrators to understand the problem in a specific workplace: “You have to know what’s going on in your organization to intervene on it,” she said. “There are multiple tools that have been validated in other health care fields and can be used on a regular basis over time to measure burnout, satisfaction, and engagement.”

For individuals, other strategies include daily check-ins with colleagues to catch signs of stress, she said, as Toronto oncologists started doing amid the pandemic. The check-ins can include simple questions like: How are you doing? How are you feeling? Are you sleeping, eating and exercising? Do you need help?

As for resilience, Hlubocky said it must grow at the individual level. “We can't rely so much on the organization. We need to develop our personal resilience in order for professional resilience to flourish again, and we have to do a lot to protect ourselves. It’s about focusing on the strength of the individual—that empowerment to rise above adversity, that vitality, that engagement, that self-efficacy. It supports health and enhances coping, and it is the key element of physician and clinician well-being.”

Research into resilience offers guidance about how to achieve it, she said. A 2013 German study of 200 physicians found that the most resilient physicians change their attitudes and behaviors, take time off, set boundaries, spend time with family and friends, and ask colleagues for help. And they gained resilience, the study found, by getting older and becoming more experienced.

Hlubocky pointed to several useful resources for burned-out medical professionals, including mindfulness, cognitive behavioral therapy and breathing apps: She highlighted Breathe2Relax, Headspace, MoodGYM, Stress Gym, and guided audio files from the University of California at San Diego. And she said ASCO has resources on combatting burnout and promoting well-being.

Hlubocky has no relevant disclosures.

SAN DIEGO—Before the pandemic, an estimated one-third of oncologists worldwide suffered a high level of burnout. Cancer physicians face many of the same risk factors as their colleagues—high workloads, lack of autonomy, and no support—along with the added pressure of working in a medical field where patients often die. Then COVID-19 hit, and the burnout crisis got even worse.

This tide can be reversed with a focus on best practices and resilience, a mental health researcher told cancer professionals at the September 2022 annual meeting of the Association of VA Hematology/Oncology. Assessments, long-term interventions, and communication are all key, said Fay J. Hlubocky, PhD, MA, a clinical health psychologist and ethicist at the University of Chicago.

Even simple actions like taking time for “mindful moments” and checking in with a colleague can make a difference, she said. But institutions must act, she said. “Long-term tailored strategies are incredibly important to promote well-being.”

Hlubocky, who led an American Society of Clinical Oncology committee on burnout prior to the pandemic, noted that statistics about burnout in American medicine and oncology specifically, are grim. In 2017, a systematic review and meta-analysis found that significant numbers of oncologists suffered from high burnout (32%), high psychiatric morbidity (27%), depression (at least 12%), and alcohol misuse (as many as 30%).

The pandemic piled on more stressors. In the second half of 2020, researchers interviewed 25 American oncologists in focus groups and found that their “underlying oncologist burnout exacerbated stressors associated with disruptions in care, education, research, financial practice health, and telemedicine. Many feared delays in cancer screening, diagnosis, and treatment [and] strongly considered working part-time or taking early retirement.”

As one participant put it, “everyone is seeing a lot of death and heartache and social isolation and anger that they’re not used to encountering and in very new and different ways.”

Major contributors to oncologist burnout, Hlubocky said, include moral distress, moral injury, and compassion fatigue. “Moral distress occurs when that individual believes he or she knows the right thing to do, but institutional constraints make it really difficult to do what is right,” Hlubocky said. “The individual is aware of the moral problem, acknowledges and takes moral responsibility, makes some moral judgments, but yet—as a result of these constraints — participates in perceived moral wrongdoing.”

Moral injury refers to the damage that can be caused by moral distress or by witnessing acts that violate morals, such as during military service. Compassion fatigue, meanwhile, is defined by the American Stress Institute as “a low level, chronic clouding of caring and concern for others in your life.”

What can be done? Hlubocky highlighted multiple interventions, such as adjustment of work patterns, cognitive behavioral therapy, and training in mindfulness, relaxation, and communication. One strategy is to adopt multiple in-person interventions simultaneously.

But first it’s crucial for administrators to understand the problem in a specific workplace: “You have to know what’s going on in your organization to intervene on it,” she said. “There are multiple tools that have been validated in other health care fields and can be used on a regular basis over time to measure burnout, satisfaction, and engagement.”

For individuals, other strategies include daily check-ins with colleagues to catch signs of stress, she said, as Toronto oncologists started doing amid the pandemic. The check-ins can include simple questions like: How are you doing? How are you feeling? Are you sleeping, eating and exercising? Do you need help?

As for resilience, Hlubocky said it must grow at the individual level. “We can't rely so much on the organization. We need to develop our personal resilience in order for professional resilience to flourish again, and we have to do a lot to protect ourselves. It’s about focusing on the strength of the individual—that empowerment to rise above adversity, that vitality, that engagement, that self-efficacy. It supports health and enhances coping, and it is the key element of physician and clinician well-being.”

Research into resilience offers guidance about how to achieve it, she said. A 2013 German study of 200 physicians found that the most resilient physicians change their attitudes and behaviors, take time off, set boundaries, spend time with family and friends, and ask colleagues for help. And they gained resilience, the study found, by getting older and becoming more experienced.

Hlubocky pointed to several useful resources for burned-out medical professionals, including mindfulness, cognitive behavioral therapy and breathing apps: She highlighted Breathe2Relax, Headspace, MoodGYM, Stress Gym, and guided audio files from the University of California at San Diego. And she said ASCO has resources on combatting burnout and promoting well-being.

Hlubocky has no relevant disclosures.

It took 609 days, but the US Senate has finally (unanimously) confirmed President Biden’s choice to head the Indian Health Service (IHS: Roselyn Tso.)

President Biden nominated Tso in March 2022, and she was formally sworn in on September 27, 2022. The long-awaited confirmation filled a space that hadn’t had a permanent director since Michael Weahkee, a Pueblo of Zuni citizen, stepped down in 2021. In the interim, Elizabeth Fowler, of the Comanche Nation, served as acting director.

Tso’s resume includes almost 40 years of professional experience working at all levels of the IHS. Before taking over as IHS director, she led the IHS Navajo area, the largest IHS regional area, managing more than 4000 employees and a budget of nearly $1 billion.

She also brings “decades of lived experience as a member of the Navajo Nation,” she said in a 40-minute Senate hearing with the US Senate Committee on Indian Affairs in May.

The first Navajo Nation citizen to head the IHS (and only the second woman to do so), Tso introduced herself in Navajo: Deeschii’nii (Start of the Red Streak People) and born for Hashk’aa hadzohi (Yucca Fruit Strung Out). “This is a historic achievement for all of our Navajo people and tribal nations across the country,” Navajo Nation President Jonathan Nez said. “To have one of our own Navajo members in the highest position with IHS is remarkable.”

Tso spoke of having to “navigate the services provided by the Agency for myself, family, and friends.” Her personal and professional backgrounds, she said, help her understand how patients experience the system and how that can be improved. “The health care provided at IHS is critical for those we serve. I understand this not just because I work there,” she said. “My family relies on IHS. My friends rely on IHS. I rely on the IHS.”

The long lacuna in confirming a permanent IHS director left the Native peoples particularly vulnerable—when the COVID-19 pandemic essentially worsened the existing problems they faced, such as diabetes mellitus and cancer. Life expectancy for Native people fell by more than 6 years between 2019 and 2021, to 65 years, compared with the US average of 76 years.

Without a full-time IHS leader, the National Council of Urban Indian Health said in a statement, tribal nations and other Native health care providers struggled to raise and address the issues they were facing amid the pandemic. “Since the resignation of Rear Admiral Weahkee, there have been countless requests from Indian Country calling on Congress and the Administration to nominate a new IHS director to address the growing health disparities experienced by AI/ANs.”

Tso laid out her priorities in her May testimony: creating a more unified health care system using the latest technology to develop centralized systems; improving accountability, transparency, and patient safety; addressing workforce needs and challenges, improving recruitment and retention.

Meeting her goals, she noted, would take “strong partnerships and communication with our Tribal partners…. Each tribe has unique needs, and those needs cannot be met if you do not understand them.”

Last year, President Joseph R. Biden asked Congress to significantly increase IHS funding, but his proposal was cut to $400 million. “For years, IHS has been funded at a rate that is far below its level of need, and the results of this historical neglect can be seen in the disparities in health outcomes for AI/AN people,” William Smith, Valdez Native Tribe, Chairman of the National Indian Health Board (NIHB), wrote to the Senate Committee on Indian Affairs, on the topic of the next IHS director. “Perhaps one of the greatest challenges facing the [Indian, tribal and urban] system is the chronic and severe underfunding and budgetary instability for health care and public health services infrastructure and delivery. Since its creation in 1955, IHS has been chronically underfunded, with annual appropriations never exceeding 50% of demonstrated need. This underfunding has contributed to substandard investment in health delivery systems, some of the worst health disparities among any US population and a severe lack of public health infrastructure and services for our people. At the start of the COVID-19 pandemic these vulnerabilities were starkly exposed and while Congress moved decisively to invest into Tribal health and public health, the new Director must work to maintain these one-time investments.”

Stacy Bohlen, NIHB chief executive, told The Oklahoman that tribal leaders will look to Tso to press Congress for more money and to secure mandatory full funding for IHS—in contrast with the current annual appropriations, where Congress includes IHS in much larger budget bills. “When those bills stall, so does the money tribal clinics need to pay employees and suppliers,” making it hard to recruit and retain employees. “In the Indian Health System,” Bohlen says, “we simply can’t afford that kind of vulnerability.”

Securing advance appropriations and, ultimately, full mandatory funding for IHS, Smith wrote in his letter to the Senate committee, “fulfills the commitment made to our people generations ago and breaks down the systemic healthcare funding inequities the federal government tolerates for Tribes.”

Tso emphasized her intent to “improve the physical, mental, social, and spiritual health and well-being of all American Indians and Alaskan Natives served by the Agency.” Tso “understands the healthcare needs that many first people of this country deal with,” President Nez said. “Her work ethic, value system and approach to problem solving demonstrates the resilience of Indigenous peoples and the commitment to combat the systemic inequities that impact tribal nations.”

It took 609 days, but the US Senate has finally (unanimously) confirmed President Biden’s choice to head the Indian Health Service (IHS: Roselyn Tso.)

President Biden nominated Tso in March 2022, and she was formally sworn in on September 27, 2022. The long-awaited confirmation filled a space that hadn’t had a permanent director since Michael Weahkee, a Pueblo of Zuni citizen, stepped down in 2021. In the interim, Elizabeth Fowler, of the Comanche Nation, served as acting director.

Tso’s resume includes almost 40 years of professional experience working at all levels of the IHS. Before taking over as IHS director, she led the IHS Navajo area, the largest IHS regional area, managing more than 4000 employees and a budget of nearly $1 billion.

She also brings “decades of lived experience as a member of the Navajo Nation,” she said in a 40-minute Senate hearing with the US Senate Committee on Indian Affairs in May.

The first Navajo Nation citizen to head the IHS (and only the second woman to do so), Tso introduced herself in Navajo: Deeschii’nii (Start of the Red Streak People) and born for Hashk’aa hadzohi (Yucca Fruit Strung Out). “This is a historic achievement for all of our Navajo people and tribal nations across the country,” Navajo Nation President Jonathan Nez said. “To have one of our own Navajo members in the highest position with IHS is remarkable.”

Tso spoke of having to “navigate the services provided by the Agency for myself, family, and friends.” Her personal and professional backgrounds, she said, help her understand how patients experience the system and how that can be improved. “The health care provided at IHS is critical for those we serve. I understand this not just because I work there,” she said. “My family relies on IHS. My friends rely on IHS. I rely on the IHS.”

The long lacuna in confirming a permanent IHS director left the Native peoples particularly vulnerable—when the COVID-19 pandemic essentially worsened the existing problems they faced, such as diabetes mellitus and cancer. Life expectancy for Native people fell by more than 6 years between 2019 and 2021, to 65 years, compared with the US average of 76 years.

Without a full-time IHS leader, the National Council of Urban Indian Health said in a statement, tribal nations and other Native health care providers struggled to raise and address the issues they were facing amid the pandemic. “Since the resignation of Rear Admiral Weahkee, there have been countless requests from Indian Country calling on Congress and the Administration to nominate a new IHS director to address the growing health disparities experienced by AI/ANs.”

Tso laid out her priorities in her May testimony: creating a more unified health care system using the latest technology to develop centralized systems; improving accountability, transparency, and patient safety; addressing workforce needs and challenges, improving recruitment and retention.

Meeting her goals, she noted, would take “strong partnerships and communication with our Tribal partners…. Each tribe has unique needs, and those needs cannot be met if you do not understand them.”

Last year, President Joseph R. Biden asked Congress to significantly increase IHS funding, but his proposal was cut to $400 million. “For years, IHS has been funded at a rate that is far below its level of need, and the results of this historical neglect can be seen in the disparities in health outcomes for AI/AN people,” William Smith, Valdez Native Tribe, Chairman of the National Indian Health Board (NIHB), wrote to the Senate Committee on Indian Affairs, on the topic of the next IHS director. “Perhaps one of the greatest challenges facing the [Indian, tribal and urban] system is the chronic and severe underfunding and budgetary instability for health care and public health services infrastructure and delivery. Since its creation in 1955, IHS has been chronically underfunded, with annual appropriations never exceeding 50% of demonstrated need. This underfunding has contributed to substandard investment in health delivery systems, some of the worst health disparities among any US population and a severe lack of public health infrastructure and services for our people. At the start of the COVID-19 pandemic these vulnerabilities were starkly exposed and while Congress moved decisively to invest into Tribal health and public health, the new Director must work to maintain these one-time investments.”

Stacy Bohlen, NIHB chief executive, told The Oklahoman that tribal leaders will look to Tso to press Congress for more money and to secure mandatory full funding for IHS—in contrast with the current annual appropriations, where Congress includes IHS in much larger budget bills. “When those bills stall, so does the money tribal clinics need to pay employees and suppliers,” making it hard to recruit and retain employees. “In the Indian Health System,” Bohlen says, “we simply can’t afford that kind of vulnerability.”

Securing advance appropriations and, ultimately, full mandatory funding for IHS, Smith wrote in his letter to the Senate committee, “fulfills the commitment made to our people generations ago and breaks down the systemic healthcare funding inequities the federal government tolerates for Tribes.”

Tso emphasized her intent to “improve the physical, mental, social, and spiritual health and well-being of all American Indians and Alaskan Natives served by the Agency.” Tso “understands the healthcare needs that many first people of this country deal with,” President Nez said. “Her work ethic, value system and approach to problem solving demonstrates the resilience of Indigenous peoples and the commitment to combat the systemic inequities that impact tribal nations.”

It took 609 days, but the US Senate has finally (unanimously) confirmed President Biden’s choice to head the Indian Health Service (IHS: Roselyn Tso.)

President Biden nominated Tso in March 2022, and she was formally sworn in on September 27, 2022. The long-awaited confirmation filled a space that hadn’t had a permanent director since Michael Weahkee, a Pueblo of Zuni citizen, stepped down in 2021. In the interim, Elizabeth Fowler, of the Comanche Nation, served as acting director.

Tso’s resume includes almost 40 years of professional experience working at all levels of the IHS. Before taking over as IHS director, she led the IHS Navajo area, the largest IHS regional area, managing more than 4000 employees and a budget of nearly $1 billion.

She also brings “decades of lived experience as a member of the Navajo Nation,” she said in a 40-minute Senate hearing with the US Senate Committee on Indian Affairs in May.

The first Navajo Nation citizen to head the IHS (and only the second woman to do so), Tso introduced herself in Navajo: Deeschii’nii (Start of the Red Streak People) and born for Hashk’aa hadzohi (Yucca Fruit Strung Out). “This is a historic achievement for all of our Navajo people and tribal nations across the country,” Navajo Nation President Jonathan Nez said. “To have one of our own Navajo members in the highest position with IHS is remarkable.”

Tso spoke of having to “navigate the services provided by the Agency for myself, family, and friends.” Her personal and professional backgrounds, she said, help her understand how patients experience the system and how that can be improved. “The health care provided at IHS is critical for those we serve. I understand this not just because I work there,” she said. “My family relies on IHS. My friends rely on IHS. I rely on the IHS.”

The long lacuna in confirming a permanent IHS director left the Native peoples particularly vulnerable—when the COVID-19 pandemic essentially worsened the existing problems they faced, such as diabetes mellitus and cancer. Life expectancy for Native people fell by more than 6 years between 2019 and 2021, to 65 years, compared with the US average of 76 years.

Without a full-time IHS leader, the National Council of Urban Indian Health said in a statement, tribal nations and other Native health care providers struggled to raise and address the issues they were facing amid the pandemic. “Since the resignation of Rear Admiral Weahkee, there have been countless requests from Indian Country calling on Congress and the Administration to nominate a new IHS director to address the growing health disparities experienced by AI/ANs.”

Tso laid out her priorities in her May testimony: creating a more unified health care system using the latest technology to develop centralized systems; improving accountability, transparency, and patient safety; addressing workforce needs and challenges, improving recruitment and retention.

Meeting her goals, she noted, would take “strong partnerships and communication with our Tribal partners…. Each tribe has unique needs, and those needs cannot be met if you do not understand them.”

Last year, President Joseph R. Biden asked Congress to significantly increase IHS funding, but his proposal was cut to $400 million. “For years, IHS has been funded at a rate that is far below its level of need, and the results of this historical neglect can be seen in the disparities in health outcomes for AI/AN people,” William Smith, Valdez Native Tribe, Chairman of the National Indian Health Board (NIHB), wrote to the Senate Committee on Indian Affairs, on the topic of the next IHS director. “Perhaps one of the greatest challenges facing the [Indian, tribal and urban] system is the chronic and severe underfunding and budgetary instability for health care and public health services infrastructure and delivery. Since its creation in 1955, IHS has been chronically underfunded, with annual appropriations never exceeding 50% of demonstrated need. This underfunding has contributed to substandard investment in health delivery systems, some of the worst health disparities among any US population and a severe lack of public health infrastructure and services for our people. At the start of the COVID-19 pandemic these vulnerabilities were starkly exposed and while Congress moved decisively to invest into Tribal health and public health, the new Director must work to maintain these one-time investments.”

Stacy Bohlen, NIHB chief executive, told The Oklahoman that tribal leaders will look to Tso to press Congress for more money and to secure mandatory full funding for IHS—in contrast with the current annual appropriations, where Congress includes IHS in much larger budget bills. “When those bills stall, so does the money tribal clinics need to pay employees and suppliers,” making it hard to recruit and retain employees. “In the Indian Health System,” Bohlen says, “we simply can’t afford that kind of vulnerability.”

Securing advance appropriations and, ultimately, full mandatory funding for IHS, Smith wrote in his letter to the Senate committee, “fulfills the commitment made to our people generations ago and breaks down the systemic healthcare funding inequities the federal government tolerates for Tribes.”

Tso emphasized her intent to “improve the physical, mental, social, and spiritual health and well-being of all American Indians and Alaskan Natives served by the Agency.” Tso “understands the healthcare needs that many first people of this country deal with,” President Nez said. “Her work ethic, value system and approach to problem solving demonstrates the resilience of Indigenous peoples and the commitment to combat the systemic inequities that impact tribal nations.”

The Diagnosis: Metastatic Carcinoid Tumor

Carcinoid tumors are derived from neuroendocrine cell compartments and generally arise in the gastrointestinal tract, with a quarter of carcinoids arising in the small bowel.¹ Carcinoid tumors have an incidence of approximately 2 to 5 per 100,000 patients.² Metastasis of carcinoids is approximately 31.2% to 46.7%.¹ Metastasis to the skin is uncommon; we present a rare case of a carcinoid tumor of the terminal ileum with metastasis to the scalp.

Unlike our patient, most patients with carcinoid tumors have an indolent clinical course. The most common cutaneous symptom is flushing, which occurs in 75% of patients.³ Secreted vasoactive peptides such as serotonin may cause other symptoms such as tachycardia, diarrhea, and bronchospasm; together, these symptoms comprise carcinoid syndrome. Carcinoid syndrome requires metastasis of the tumor to the liver or a site outside of the gastrointestinal tract because the liver will metabolize the secreted serotonin. However, even in patients with liver metastasis, carcinoid syndrome only occurs in approximately 10% of patients.⁴ Common skin findings of carcinoid syndrome include pellagralike dermatitis, flushing, and sclerodermalike changes.⁵ Our patient experienced several episodes of presyncope with symptoms of dyspnea, lightheadedness, and flushing but did not have bronchospasm or recurrent diarrhea. Intramuscular octreotide improved some symptoms.

The scalp accounts for approximately 15% of cutaneous metastases, the most common being from the lung, renal, and breast cancers.⁶ Cutaneous metastases of carcinoid tumors are rare. A PubMed search of articles indexed for MEDLINE using the terms metastatic AND [carcinoid OR neuroendocrine] tumors AND [skin OR cutaneous] revealed 47 cases.^7-11 Similar to other skin metastases, cutaneous metastases of carcinoid tumors commonly present as firm erythematous nodules of varying sizes that may be asymptomatic, tender, or pruritic (Figure 1). Cases of carcinoid tumors with cutaneous metastasis as the initial and only presenting sign are exceedingly rare.¹²

Histology of carcinoid tumors reveals a dermal neoplasm composed of loosely cohesive, mildly atypical, polygonal cells with salt-and-pepper chromatin and eosinophilic cytoplasm, which are similar findings to the primary tumor. The cells may grow in the typical trabecular or organoid neuroendocrine pattern or exhibit a pseudoglandular growth pattern with prominent vessels (quiz image, top).¹² Positive chromogranin and synaptophysin immunostaining are the most common and reliable markers used for the diagnosis of carcinoid tumors.

An important histopathologic differential diagnosis is the aggressive Merkel cell carcinoma, which also demonstrates homogenous salt-and-pepper chromatin but exhibits a higher mitotic rate and positive cytokeratin 20 staining (Figure 2).¹³ Basal cell carcinoma (BCC) also may display similar features, including a blue tumor at scanning magnification and nodular or infiltrative growth patterns. The cell morphology of BCC is characterized by islands of basaloid cells with minimal cytoplasm and frequent apoptosis, connecting to the epidermis with peripheral palisading, retraction artifact, and a myxoid stroma; BCC lacks the salt-and-pepper chromatin commonly seen in carcinoid tumors (Figure 3). Basal cell carcinoma is characterized by positive BerEP4 (epithelial cell adhesion molecule immunostain), cytokeratin 5/6, and cytokeratin 14 uptake. Cytokeratin 20, often used to diagnose Merkel cell carcinoma, is negative in BCC. Chromogranin and synaptophysin occasionally may be positive in BCC.¹⁴

The superficial Ewing sarcoma family of tumors also may be included in the differential diagnosis of small round cell tumors of the skin, but they are very rare. These tumors possess strong positive membranous staining of cytokeratin 99 and also can stain positively for synaptophysin and chromogranin.¹⁵ Epithelial membrane antigen, which is negative in Ewing sarcomas, is positive in carcinoid tumors.¹⁶ Neuroendocrine tumors of all sites share similar basic morphologic patterns, and multiple primary tumors should be considered, including small cell lung carcinoma (Figure 4).^17,18 Red granulations and true glandular lumina typically are not seen in the lungs but are common in gastrointestinal carcinoids.¹⁸ Regarding immunohistochemistry, TTF-1 is negative and CDX2 is positive in gastroenteropancreatic carcinoids, suggesting that these 2 markers can help distinguish carcinoids of unknown primary origin.¹⁹

Metastases in carcinoid tumors are common, with one study noting that the highest frequency of small intestinal metastases was from the ileal subset.²⁰ At the time of diagnosis, 58% to 64% of patients with small intestine carcinoid tumors already had nonlocalized disease, with frequent sites being the lymph nodes (89.8%), liver (44.1%), lungs (13.6%), and peritoneum (13.6%). Regional and distant metastases are associated with substantially worse prognoses, with survival rates of 71.7% and 38.5%, respectively.¹ Treatment of symptomatic unresectable disease focuses on symptomatic management with somatostatin analogs that also control tumor growth.²¹

We present a rare case of scalp metastasis of a carcinoid tumor of the terminal ileum. Distant metastasis is associated with poorer prognosis and should be considered in patients with a known history of a carcinoid tumor.

Acknowledgment—We would like to acknowledge the Research Histology and Tissue Imaging Core at University of Illinois Chicago Research Resources Center for the immunohistochemistry studies.

The Diagnosis: Metastatic Carcinoid Tumor

Carcinoid tumors are derived from neuroendocrine cell compartments and generally arise in the gastrointestinal tract, with a quarter of carcinoids arising in the small bowel.¹ Carcinoid tumors have an incidence of approximately 2 to 5 per 100,000 patients.² Metastasis of carcinoids is approximately 31.2% to 46.7%.¹ Metastasis to the skin is uncommon; we present a rare case of a carcinoid tumor of the terminal ileum with metastasis to the scalp.

Unlike our patient, most patients with carcinoid tumors have an indolent clinical course. The most common cutaneous symptom is flushing, which occurs in 75% of patients.³ Secreted vasoactive peptides such as serotonin may cause other symptoms such as tachycardia, diarrhea, and bronchospasm; together, these symptoms comprise carcinoid syndrome. Carcinoid syndrome requires metastasis of the tumor to the liver or a site outside of the gastrointestinal tract because the liver will metabolize the secreted serotonin. However, even in patients with liver metastasis, carcinoid syndrome only occurs in approximately 10% of patients.⁴ Common skin findings of carcinoid syndrome include pellagralike dermatitis, flushing, and sclerodermalike changes.⁵ Our patient experienced several episodes of presyncope with symptoms of dyspnea, lightheadedness, and flushing but did not have bronchospasm or recurrent diarrhea. Intramuscular octreotide improved some symptoms.

The scalp accounts for approximately 15% of cutaneous metastases, the most common being from the lung, renal, and breast cancers.⁶ Cutaneous metastases of carcinoid tumors are rare. A PubMed search of articles indexed for MEDLINE using the terms metastatic AND [carcinoid OR neuroendocrine] tumors AND [skin OR cutaneous] revealed 47 cases.^7-11 Similar to other skin metastases, cutaneous metastases of carcinoid tumors commonly present as firm erythematous nodules of varying sizes that may be asymptomatic, tender, or pruritic (Figure 1). Cases of carcinoid tumors with cutaneous metastasis as the initial and only presenting sign are exceedingly rare.¹²

Histology of carcinoid tumors reveals a dermal neoplasm composed of loosely cohesive, mildly atypical, polygonal cells with salt-and-pepper chromatin and eosinophilic cytoplasm, which are similar findings to the primary tumor. The cells may grow in the typical trabecular or organoid neuroendocrine pattern or exhibit a pseudoglandular growth pattern with prominent vessels (quiz image, top).¹² Positive chromogranin and synaptophysin immunostaining are the most common and reliable markers used for the diagnosis of carcinoid tumors.

An important histopathologic differential diagnosis is the aggressive Merkel cell carcinoma, which also demonstrates homogenous salt-and-pepper chromatin but exhibits a higher mitotic rate and positive cytokeratin 20 staining (Figure 2).¹³ Basal cell carcinoma (BCC) also may display similar features, including a blue tumor at scanning magnification and nodular or infiltrative growth patterns. The cell morphology of BCC is characterized by islands of basaloid cells with minimal cytoplasm and frequent apoptosis, connecting to the epidermis with peripheral palisading, retraction artifact, and a myxoid stroma; BCC lacks the salt-and-pepper chromatin commonly seen in carcinoid tumors (Figure 3). Basal cell carcinoma is characterized by positive BerEP4 (epithelial cell adhesion molecule immunostain), cytokeratin 5/6, and cytokeratin 14 uptake. Cytokeratin 20, often used to diagnose Merkel cell carcinoma, is negative in BCC. Chromogranin and synaptophysin occasionally may be positive in BCC.¹⁴

The superficial Ewing sarcoma family of tumors also may be included in the differential diagnosis of small round cell tumors of the skin, but they are very rare. These tumors possess strong positive membranous staining of cytokeratin 99 and also can stain positively for synaptophysin and chromogranin.¹⁵ Epithelial membrane antigen, which is negative in Ewing sarcomas, is positive in carcinoid tumors.¹⁶ Neuroendocrine tumors of all sites share similar basic morphologic patterns, and multiple primary tumors should be considered, including small cell lung carcinoma (Figure 4).^17,18 Red granulations and true glandular lumina typically are not seen in the lungs but are common in gastrointestinal carcinoids.¹⁸ Regarding immunohistochemistry, TTF-1 is negative and CDX2 is positive in gastroenteropancreatic carcinoids, suggesting that these 2 markers can help distinguish carcinoids of unknown primary origin.¹⁹

Metastases in carcinoid tumors are common, with one study noting that the highest frequency of small intestinal metastases was from the ileal subset.²⁰ At the time of diagnosis, 58% to 64% of patients with small intestine carcinoid tumors already had nonlocalized disease, with frequent sites being the lymph nodes (89.8%), liver (44.1%), lungs (13.6%), and peritoneum (13.6%). Regional and distant metastases are associated with substantially worse prognoses, with survival rates of 71.7% and 38.5%, respectively.¹ Treatment of symptomatic unresectable disease focuses on symptomatic management with somatostatin analogs that also control tumor growth.²¹

We present a rare case of scalp metastasis of a carcinoid tumor of the terminal ileum. Distant metastasis is associated with poorer prognosis and should be considered in patients with a known history of a carcinoid tumor.

Acknowledgment—We would like to acknowledge the Research Histology and Tissue Imaging Core at University of Illinois Chicago Research Resources Center for the immunohistochemistry studies.

The Diagnosis: Metastatic Carcinoid Tumor

Carcinoid tumors are derived from neuroendocrine cell compartments and generally arise in the gastrointestinal tract, with a quarter of carcinoids arising in the small bowel.¹ Carcinoid tumors have an incidence of approximately 2 to 5 per 100,000 patients.² Metastasis of carcinoids is approximately 31.2% to 46.7%.¹ Metastasis to the skin is uncommon; we present a rare case of a carcinoid tumor of the terminal ileum with metastasis to the scalp.

Unlike our patient, most patients with carcinoid tumors have an indolent clinical course. The most common cutaneous symptom is flushing, which occurs in 75% of patients.³ Secreted vasoactive peptides such as serotonin may cause other symptoms such as tachycardia, diarrhea, and bronchospasm; together, these symptoms comprise carcinoid syndrome. Carcinoid syndrome requires metastasis of the tumor to the liver or a site outside of the gastrointestinal tract because the liver will metabolize the secreted serotonin. However, even in patients with liver metastasis, carcinoid syndrome only occurs in approximately 10% of patients.⁴ Common skin findings of carcinoid syndrome include pellagralike dermatitis, flushing, and sclerodermalike changes.⁵ Our patient experienced several episodes of presyncope with symptoms of dyspnea, lightheadedness, and flushing but did not have bronchospasm or recurrent diarrhea. Intramuscular octreotide improved some symptoms.

The scalp accounts for approximately 15% of cutaneous metastases, the most common being from the lung, renal, and breast cancers.⁶ Cutaneous metastases of carcinoid tumors are rare. A PubMed search of articles indexed for MEDLINE using the terms metastatic AND [carcinoid OR neuroendocrine] tumors AND [skin OR cutaneous] revealed 47 cases.^7-11 Similar to other skin metastases, cutaneous metastases of carcinoid tumors commonly present as firm erythematous nodules of varying sizes that may be asymptomatic, tender, or pruritic (Figure 1). Cases of carcinoid tumors with cutaneous metastasis as the initial and only presenting sign are exceedingly rare.¹²

Histology of carcinoid tumors reveals a dermal neoplasm composed of loosely cohesive, mildly atypical, polygonal cells with salt-and-pepper chromatin and eosinophilic cytoplasm, which are similar findings to the primary tumor. The cells may grow in the typical trabecular or organoid neuroendocrine pattern or exhibit a pseudoglandular growth pattern with prominent vessels (quiz image, top).¹² Positive chromogranin and synaptophysin immunostaining are the most common and reliable markers used for the diagnosis of carcinoid tumors.

An important histopathologic differential diagnosis is the aggressive Merkel cell carcinoma, which also demonstrates homogenous salt-and-pepper chromatin but exhibits a higher mitotic rate and positive cytokeratin 20 staining (Figure 2).¹³ Basal cell carcinoma (BCC) also may display similar features, including a blue tumor at scanning magnification and nodular or infiltrative growth patterns. The cell morphology of BCC is characterized by islands of basaloid cells with minimal cytoplasm and frequent apoptosis, connecting to the epidermis with peripheral palisading, retraction artifact, and a myxoid stroma; BCC lacks the salt-and-pepper chromatin commonly seen in carcinoid tumors (Figure 3). Basal cell carcinoma is characterized by positive BerEP4 (epithelial cell adhesion molecule immunostain), cytokeratin 5/6, and cytokeratin 14 uptake. Cytokeratin 20, often used to diagnose Merkel cell carcinoma, is negative in BCC. Chromogranin and synaptophysin occasionally may be positive in BCC.¹⁴

The superficial Ewing sarcoma family of tumors also may be included in the differential diagnosis of small round cell tumors of the skin, but they are very rare. These tumors possess strong positive membranous staining of cytokeratin 99 and also can stain positively for synaptophysin and chromogranin.¹⁵ Epithelial membrane antigen, which is negative in Ewing sarcomas, is positive in carcinoid tumors.¹⁶ Neuroendocrine tumors of all sites share similar basic morphologic patterns, and multiple primary tumors should be considered, including small cell lung carcinoma (Figure 4).^17,18 Red granulations and true glandular lumina typically are not seen in the lungs but are common in gastrointestinal carcinoids.¹⁸ Regarding immunohistochemistry, TTF-1 is negative and CDX2 is positive in gastroenteropancreatic carcinoids, suggesting that these 2 markers can help distinguish carcinoids of unknown primary origin.¹⁹

Metastases in carcinoid tumors are common, with one study noting that the highest frequency of small intestinal metastases was from the ileal subset.²⁰ At the time of diagnosis, 58% to 64% of patients with small intestine carcinoid tumors already had nonlocalized disease, with frequent sites being the lymph nodes (89.8%), liver (44.1%), lungs (13.6%), and peritoneum (13.6%). Regional and distant metastases are associated with substantially worse prognoses, with survival rates of 71.7% and 38.5%, respectively.¹ Treatment of symptomatic unresectable disease focuses on symptomatic management with somatostatin analogs that also control tumor growth.²¹

We present a rare case of scalp metastasis of a carcinoid tumor of the terminal ileum. Distant metastasis is associated with poorer prognosis and should be considered in patients with a known history of a carcinoid tumor.

Acknowledgment—We would like to acknowledge the Research Histology and Tissue Imaging Core at University of Illinois Chicago Research Resources Center for the immunohistochemistry studies.

Misoprostol: Clinical pharmacology in obstetrics and gynecology

ROBERT L. BARBIERI, MD (JULY 2022)

Outcomes from my practice’s pilot study

In his recent editorial, Dr. Barbieri addressed the important topic of office-based cervical ripening prior to inpatient induction of labor. In order to decrease the length of labor and increase the success of vaginal delivery, the cervical factor is of prime importance. Patients with an unfavorable cervix (Bishop score of ≥6) are more likely to experience longer labor, risk of infection, fetal distress, etc, and may end up with an unwanted cesarean delivery. To prevent the above, numerous approaches (mechanical methods, double-balloon catheter, laminaria, misoprostol among others) have been discussed.

The inclusion criteria for office-based cervical ripening are low-risk patients, singleton pregnancies between 39 and 40 weeks of gestation, and cephalic presentation. The details of inclusion and exclusion criteria have to be determined by each practice individually. Our practice went a step further. We performed a small pilot study to assess the safety and efficacy of office cervical ripening in low-risk primigravid patients with low Bishop scores who were not scheduled for induction in anticipation of labor. Ten primigravid patients with poor Bishop scores (6 or less) were administered 50 µg misoprostol at 39+ weeks of pregnancy in the office setting. Bishop scores were taken twice per week until delivery. In 7 out of 10 patients, the Bishop score became favorable within a week of treatment, and in 3 patients the Bishop score remained the same. Three out of 10 patients experienced self-limited episodes of uterine contractility, and 2 of the patients went into labor within 3 days of using misoprostol. All patients were delivered within 2 weeks of treatment without an induction: 8 delivered vaginally, and 2 by cesarean delivery.²

Cesarean delivery was done for fetal distress (1 case) and prolonged second stage of labor (1 case). All neonates were born in satisfactory condition with Apgar scores between 7 and 10. Our preliminary results demonstrated marked improvement in cervical ripening judged by the Bishop score in 70% of patients.²

A prospective randomized study should be performed with the following agenda:

• Does late pregnancy medical cervical ripening in low-risk patients affect labor course and cesarean delivery rate?
• What is the optimal dose and route of administration of misoprostol?^3,4

References

1. Barbieri R. Office-based ambulatory cervical ripening prior to in patient induction of labor. OBG Manag. 2021;33:9-13.
2. Petrikovsky B. Should cervical ripening become routine in primigravid low risk patients [In press]. Neonat Int Care. 2022:1, 4-6.
3. Sharami SH, Milani F, Faraji R. Comparison of 25 µg sublingual and 50 µg intravaginal misoprostol for cervical ripening and labor: a randomized controlled equivalence trial. Arch Med. 2014:10:653-656.
4. Barbieri R. Misoprostol: clinical pharmacology in obstetrics and gynecology. OBG Manag. 2022:34:7, 8-12.

B. Petrikovsky, MD, PhD

New Hyde Park, New York

Dr. Barbieri responds

I appreciate that Dr. Petrikovsky took time from a busy practice to provide our readers with his very innovative idea. I agree with him that a clinical trial is warranted to test the effects of late pregnancy medical cervical ripening in low-risk patients on labor course and birth outcome. Maybe one of our readers will take on the challenge to complete such a trial! ●

Misoprostol: Clinical pharmacology in obstetrics and gynecology

ROBERT L. BARBIERI, MD (JULY 2022)

Outcomes from my practice’s pilot study

In his recent editorial, Dr. Barbieri addressed the important topic of office-based cervical ripening prior to inpatient induction of labor. In order to decrease the length of labor and increase the success of vaginal delivery, the cervical factor is of prime importance. Patients with an unfavorable cervix (Bishop score of ≥6) are more likely to experience longer labor, risk of infection, fetal distress, etc, and may end up with an unwanted cesarean delivery. To prevent the above, numerous approaches (mechanical methods, double-balloon catheter, laminaria, misoprostol among others) have been discussed.

The inclusion criteria for office-based cervical ripening are low-risk patients, singleton pregnancies between 39 and 40 weeks of gestation, and cephalic presentation. The details of inclusion and exclusion criteria have to be determined by each practice individually. Our practice went a step further. We performed a small pilot study to assess the safety and efficacy of office cervical ripening in low-risk primigravid patients with low Bishop scores who were not scheduled for induction in anticipation of labor. Ten primigravid patients with poor Bishop scores (6 or less) were administered 50 µg misoprostol at 39+ weeks of pregnancy in the office setting. Bishop scores were taken twice per week until delivery. In 7 out of 10 patients, the Bishop score became favorable within a week of treatment, and in 3 patients the Bishop score remained the same. Three out of 10 patients experienced self-limited episodes of uterine contractility, and 2 of the patients went into labor within 3 days of using misoprostol. All patients were delivered within 2 weeks of treatment without an induction: 8 delivered vaginally, and 2 by cesarean delivery.²

Cesarean delivery was done for fetal distress (1 case) and prolonged second stage of labor (1 case). All neonates were born in satisfactory condition with Apgar scores between 7 and 10. Our preliminary results demonstrated marked improvement in cervical ripening judged by the Bishop score in 70% of patients.²

A prospective randomized study should be performed with the following agenda:

• Does late pregnancy medical cervical ripening in low-risk patients affect labor course and cesarean delivery rate?
• What is the optimal dose and route of administration of misoprostol?^3,4

References

1. Barbieri R. Office-based ambulatory cervical ripening prior to in patient induction of labor. OBG Manag. 2021;33:9-13.
2. Petrikovsky B. Should cervical ripening become routine in primigravid low risk patients [In press]. Neonat Int Care. 2022:1, 4-6.
3. Sharami SH, Milani F, Faraji R. Comparison of 25 µg sublingual and 50 µg intravaginal misoprostol for cervical ripening and labor: a randomized controlled equivalence trial. Arch Med. 2014:10:653-656.
4. Barbieri R. Misoprostol: clinical pharmacology in obstetrics and gynecology. OBG Manag. 2022:34:7, 8-12.

B. Petrikovsky, MD, PhD

New Hyde Park, New York

Dr. Barbieri responds

I appreciate that Dr. Petrikovsky took time from a busy practice to provide our readers with his very innovative idea. I agree with him that a clinical trial is warranted to test the effects of late pregnancy medical cervical ripening in low-risk patients on labor course and birth outcome. Maybe one of our readers will take on the challenge to complete such a trial! ●

Misoprostol: Clinical pharmacology in obstetrics and gynecology

ROBERT L. BARBIERI, MD (JULY 2022)

Outcomes from my practice’s pilot study

In his recent editorial, Dr. Barbieri addressed the important topic of office-based cervical ripening prior to inpatient induction of labor. In order to decrease the length of labor and increase the success of vaginal delivery, the cervical factor is of prime importance. Patients with an unfavorable cervix (Bishop score of ≥6) are more likely to experience longer labor, risk of infection, fetal distress, etc, and may end up with an unwanted cesarean delivery. To prevent the above, numerous approaches (mechanical methods, double-balloon catheter, laminaria, misoprostol among others) have been discussed.

The inclusion criteria for office-based cervical ripening are low-risk patients, singleton pregnancies between 39 and 40 weeks of gestation, and cephalic presentation. The details of inclusion and exclusion criteria have to be determined by each practice individually. Our practice went a step further. We performed a small pilot study to assess the safety and efficacy of office cervical ripening in low-risk primigravid patients with low Bishop scores who were not scheduled for induction in anticipation of labor. Ten primigravid patients with poor Bishop scores (6 or less) were administered 50 µg misoprostol at 39+ weeks of pregnancy in the office setting. Bishop scores were taken twice per week until delivery. In 7 out of 10 patients, the Bishop score became favorable within a week of treatment, and in 3 patients the Bishop score remained the same. Three out of 10 patients experienced self-limited episodes of uterine contractility, and 2 of the patients went into labor within 3 days of using misoprostol. All patients were delivered within 2 weeks of treatment without an induction: 8 delivered vaginally, and 2 by cesarean delivery.²

Cesarean delivery was done for fetal distress (1 case) and prolonged second stage of labor (1 case). All neonates were born in satisfactory condition with Apgar scores between 7 and 10. Our preliminary results demonstrated marked improvement in cervical ripening judged by the Bishop score in 70% of patients.²

A prospective randomized study should be performed with the following agenda:

• Does late pregnancy medical cervical ripening in low-risk patients affect labor course and cesarean delivery rate?
• What is the optimal dose and route of administration of misoprostol?^3,4

References

1. Barbieri R. Office-based ambulatory cervical ripening prior to in patient induction of labor. OBG Manag. 2021;33:9-13.
2. Petrikovsky B. Should cervical ripening become routine in primigravid low risk patients [In press]. Neonat Int Care. 2022:1, 4-6.
3. Sharami SH, Milani F, Faraji R. Comparison of 25 µg sublingual and 50 µg intravaginal misoprostol for cervical ripening and labor: a randomized controlled equivalence trial. Arch Med. 2014:10:653-656.
4. Barbieri R. Misoprostol: clinical pharmacology in obstetrics and gynecology. OBG Manag. 2022:34:7, 8-12.

B. Petrikovsky, MD, PhD

New Hyde Park, New York

Dr. Barbieri responds

I appreciate that Dr. Petrikovsky took time from a busy practice to provide our readers with his very innovative idea. I agree with him that a clinical trial is warranted to test the effects of late pregnancy medical cervical ripening in low-risk patients on labor course and birth outcome. Maybe one of our readers will take on the challenge to complete such a trial! ●

ILLUSTRATION: COPYRIGHT KIMBERLY MARTENS FOR OBG MANAGEMENT

CASE Patient desires prolapse repair

A 65-year-old postmenopausal patient (G3P3) presents to your office with symptoms of a vaginal bulge for more than 1 year. She has no urinary incontinence symptoms and no bowel dysfunction symptoms. On examination, you diagnose stage 2 uterovaginal prolapse with both anterior and apical defects. The patient declines expectant and pessary management and desires surgery, but she states that she feels her uterus “is important for me to keep, as my babies grew in there and it is part of me.” She denies any family or personal history of breast, endometrial, or ovarian cancer and has no history of abnormal cervical cancer screening or postmenopausal bleeding. What are the options for this patient?

Who is the appropriate hysteropexy patient, and how do we counsel her?

Uterine prolapse is the third leading cause of benign hysterectomy, with approximately 70,000 procedures performed each year in the United States. It has long been acknowledged that the uterus is a passive bystander to the prolapse process,¹ but modern practice often involves a hysterectomy as part of addressing apical prolapse. However, more and more uterine-preserving surgeries are being performed, with one study showing an increase from 1.8% to 5% from 2002 and 2012.²

When presented with the option to keep or remove their uterus during the time of prolapse surgery, 36% of patients indicated that they would prefer to keep their uterus with similar outcomes while 21% would still prefer uterine preservation even if outcomes were inferior compared with hysterectomy.³ Another study showed that 60% of patients would decline concurrent hysterectomy if there were equal surgical outcomes,⁴ and popular platforms, such as Health magazine (www.health.com) and AARP magazine (www.aarp.org), have listed benign hysterectomy as a “top surgery to avoid.”

Patients desire uterine preservation for many reasons, including concerns about sexual function and pleasure, the uterus being important to their sense of identity or womanhood, and concerns around menopausal symptoms. Early patient counseling and discussion of surgical goals can help clinicians fully understand a patient’s thoughts toward uterine preservation. Women who identified their uterus as important to their sense of self had a 28.2-times chance of preferring uterine preservation.³ Frequently, concerns about menopausal symptoms are more directly related to hormones and ovary removal, not uterus removal, but clinicians should be careful to also counsel patients on the increased risk of menopause in the 5 years after hysterectomy, even with ovarian preservation.⁵

There are some patients for whom experts do not recommend uterine preservation.⁶ Patients with an increased risk of cervical or endometrial pathology should be counseled on the benefits of hysterectomy. Additionally, patients who have abnormal uterine bleeding from benign pathology should consider hysterectomy to treat these issues and avoid future workups (TABLE). For postmenopausal patients with recent postmenopausal bleeding, we encourage hysterectomy. A study of patients undergoing hysterectomy at the time of prolapse repair found a rate of 13% unanticipated endometrial pathology with postmenopausal bleeding and negative preoperative workup.⁷

At this time, a majority of clinicians consider the desire for future fertility to be a relative contraindication to surgical prolapse repair and advise conservative management with pessary until childbearing is complete. This is reasonable, given the paucity of safety data in subsequent pregnancies as well as the lack of prolapse outcomes after those pregnancies.^8,9 Lastly, cervical elongation is considered a relative contraindication, as it represents a risk for surgical failure.^10,11 This may be counteracted with trachelectomy at the time of hysteropexy or surgeries such as the Manchester repair, which involve a trachelectomy routinely,¹² but currently there is no strong evidence for this as routine practice.

Continue to: Uterine preservation surgical techniques and outcomes...

Uterine preservation surgical techniques and outcomes

Le Fort colpocleisis

First described in 1840 by Neugebauer of Poland and later by Le Fort in Paris in 1877, the Le Fort colpocleisis repair technique remains the most reliable prolapse surgery to date.¹⁴ The uterus is left in place while the vagina is narrowed and shortened. It typically also is performed with a levator plication to reduce the genital hiatus.

This procedure is quick and effective, with a 90% to 95% success rate. If necessary, it can be performed under local or regional anesthesia, making it a good option for medically frail patients. It is not an option for everyone, however, as penetrative intercourse is no longer an option after surgery. Studies suggest an approximately 13% dissatisfaction rate after the procedure, with most of that coming from postoperative urinary symptoms, such as urgency or stress incontinence,¹⁵ and some studies show a dissatisfaction rate as low as 0% in a well-counseled patient population.^16,17

Vaginal native tissue hysteropexy

Many patients who elect for uterine preservation at the time of prolapse surgery are “minimalists,” meaning that a vaginal native tissue procedure appeals to them due to the lack of abdominal incisions, decreased operating room time, and lack of permanent graft materials.

Of all the hysteropexy procedures, sacrospinous hysteropexy (SSHP) has the most robust data available. The approach to SSHP can be tailored to the patient’s anatomy and it is performed in a manner similar to posthysterectomy sacrospinous ligament fixation. The traditional posterior approach can be used with predominantly posterior prolapse, while an apical approach through a semilunar paracervical incision can be used for predominantly apical prolapse. Expert surgeons agree that one key to success is anchoring the suspension sutures through the cervical stroma, not just the vaginal epithelium.

Researchers in the Netherlands published the 5-year outcomes of a randomized trial that compared SSHP with vaginal hysterectomy with uterosacral ligament suspension.¹⁸ Their data showed no difference between groups in composite failure, reoperation rates, quality of life measures, and postoperative sexual function. Adverse events were very similar to those reported for posthysterectomy sacrospinous ligament fixation, including 15% transient buttock pain. Of note, the same authors explored risk factors for recurrence after SSHP and found that higher body mass index, smoking, and a large point Ba measurement were risk factors for prolapse recurrence.¹⁹

A randomized, controlled trial in the United Kingdom (the VUE trial) compared vaginal hysterectomy with apical suspension to uterine preservation with a variety of apical suspension techniques, mostly SSHP, and demonstrated no significant differences in outcomes.²⁰ Overall, SSHP is an excellent option for many patients interested in uterine preservation.

Uterosacral ligament hysteropexy (USHP), when performed vaginally, is very similar to uterosacral ligament suspension at the time of vaginal hysterectomy, with entry into the peritoneal cavity through a posterior colpotomy. The uterosacral ligaments are grasped and delayed absorbable suture placed through the ligaments and anchored into the posterior cervical stroma. Given the maintenance of the normal axis of the vagina, USHP is a good technique for patients with isolated apical defects. Unfortunately, the least amount of quality data is available for USHP at this time. Currently, evidence suggests that complications are rare and that the procedure may offer acceptable anatomic and symptomatic outcomes.²¹ Some surgeons approach the uterosacral suspension laparoscopically, which also has mixed results in the literature, with failure rates between 8% and 27% and few robust studies.^22–24

The Manchester-Fothergill operation, currently not common in the United States but popular in Europe, primarily is considered a treatment for cervical elongation when the uterosacral ligaments are intact. In this procedure, trachelectomy is performed and the uterosacral ligaments are plicated to the uterine body. Sturmdorf sutures are frequently placed to close off the endometrial canal, which can lead to hematometra and other complications of cervical stenosis. Previous unmatched studies have shown similar outcomes with the Manchester procedure compared with vaginal hysterectomy.^25,26

The largest study currently available is a registry study from Denmark, with matched cohort populations, that compared the Manchester procedure, SSHP, and total vaginal hysterectomy with uterosacral ligament suspension.²⁷ This study indicated less morbidity related to the Manchester procedure, decreased anterior recurrence compared with SSHP, and a 7% reoperation rate.²⁷ The same authors also established better cost-effectiveness with the Manchester procedure as opposed to vaginal hysterectomy with uterosacral ligament suspension.²⁸

Continue to: Vaginal mesh hysteropexy...

Hysteropexy using vaginal mesh is limited in the United States given the removal of vaginal mesh kits from the market by the US Food and Drug Administration in 2019. However, a Pelvic Floor Disorders Network randomized trial compared vaginal mesh hysteropexy using the Uphold LITE transvaginal mesh support system (Boston Scientific) and vaginal hysterectomy with uterosacral ligament suspension.²⁹ At 5 years, mesh hysteropexy had fewer failures than hysterectomy (37% vs 54%) and there was no difference in retreatment (9% vs 13%). The authors noted an 8% mesh exposure rate in the mesh hysteropexy group but 12% granulation tissue and 21% suture exposure rate in the hysterectomy group.²⁹

While vaginal mesh hysteropexy was effective in the treatment of apical prolapse, the elevated mesh exposure rate and postoperative complications ultimately led to its removal from the market.

Sacrohysteropexy

Lastly, prolapse surgery with uterine preservation may be accomplished abdominally, most commonly laparoscopically with or without robotic assistance.

Sacrohysteropexy (SHP) involves the attachment of permanent synthetic mesh posteriorly to the posterior vagina and cervix with or without the additional placement of mesh to the anterior vagina and cervix. When the anterior mesh is placed, the arms are typically routed through the broad ligament bilaterally and joined with the posterior mesh for attachment to the anterior longitudinal ligament, overlying the sacrum.

Proponents of this technique endorse the use of mesh to augment already failing native tissues and propose similarities to the durability of sacrocolpopexy. While no randomized controlled trials have compared hysterectomy with sacrocolpopexy or supracervical hysterectomy with sacrocolpopexy to sacrohysteropexy, a meta-analysis suggests that sacrohysteropexy may have a decreased risk of mesh exposure but a higher reoperation rate with lower anatomic success.⁹ Randomized trials that compared abdominal sacrohysteropexy with vaginal hysterectomy and suspension indicate that apical support may be improved with sacrohysteropexy,³⁰ but reoperations, postoperative pain and disability, and urinary dysfunction was higher with SHP.^31,32

What further research is needed?

With the increasing patient and clinician interest in uterine preservation, more research is needed to improve patient counseling and surgical planning. Much of the current research compares hysteropexy outcomes with those of traditional prolapse repairs with hysterectomy, with only a few randomized trials. We are lacking robust, prospective comparison studies between hysteropexy methods, especially vaginal native tissue techniques, long-term follow-up on the prevalence of uterine or cervical pathology after hysteropexy, and pregnancy or postpartum outcomes following uterine preservation surgery.

Currently, work is underway to validate and test the effectiveness of a questionnaire to evaluate the uterus’s importance to the patient seeking prolapse surgery in order to optimize counseling. The VUE trial, which randomizes women to vaginal hysterectomy with suspension versus various prolapse surgeries with uterine preservation, is continuing its 6-year follow-up.²⁰ In the Netherlands, an ongoing randomized, controlled trial (the SAM trial) is comparing the Manchester procedure with sacrospinous hysteropexy and will follow patients up to 24 months.³³ Fortunately, both of these trials are rigorously assessing both objective and patient-centered outcomes.

CASE Counseling helps the patient weigh surgical options

After thorough review of her surgical options, the patient elects for a uterine-preserving prolapse repair. She would like to have the most minimally invasive procedure and does not want any permanent mesh used. You suggest, and she agrees to, a sacrospinous ligament hysteropexy, as it is the current technique with the most robust data. ●

ILLUSTRATION: COPYRIGHT KIMBERLY MARTENS FOR OBG MANAGEMENT

CASE Patient desires prolapse repair

A 65-year-old postmenopausal patient (G3P3) presents to your office with symptoms of a vaginal bulge for more than 1 year. She has no urinary incontinence symptoms and no bowel dysfunction symptoms. On examination, you diagnose stage 2 uterovaginal prolapse with both anterior and apical defects. The patient declines expectant and pessary management and desires surgery, but she states that she feels her uterus “is important for me to keep, as my babies grew in there and it is part of me.” She denies any family or personal history of breast, endometrial, or ovarian cancer and has no history of abnormal cervical cancer screening or postmenopausal bleeding. What are the options for this patient?

Who is the appropriate hysteropexy patient, and how do we counsel her?

Uterine prolapse is the third leading cause of benign hysterectomy, with approximately 70,000 procedures performed each year in the United States. It has long been acknowledged that the uterus is a passive bystander to the prolapse process,¹ but modern practice often involves a hysterectomy as part of addressing apical prolapse. However, more and more uterine-preserving surgeries are being performed, with one study showing an increase from 1.8% to 5% from 2002 and 2012.²

When presented with the option to keep or remove their uterus during the time of prolapse surgery, 36% of patients indicated that they would prefer to keep their uterus with similar outcomes while 21% would still prefer uterine preservation even if outcomes were inferior compared with hysterectomy.³ Another study showed that 60% of patients would decline concurrent hysterectomy if there were equal surgical outcomes,⁴ and popular platforms, such as Health magazine (www.health.com) and AARP magazine (www.aarp.org), have listed benign hysterectomy as a “top surgery to avoid.”

Patients desire uterine preservation for many reasons, including concerns about sexual function and pleasure, the uterus being important to their sense of identity or womanhood, and concerns around menopausal symptoms. Early patient counseling and discussion of surgical goals can help clinicians fully understand a patient’s thoughts toward uterine preservation. Women who identified their uterus as important to their sense of self had a 28.2-times chance of preferring uterine preservation.³ Frequently, concerns about menopausal symptoms are more directly related to hormones and ovary removal, not uterus removal, but clinicians should be careful to also counsel patients on the increased risk of menopause in the 5 years after hysterectomy, even with ovarian preservation.⁵

There are some patients for whom experts do not recommend uterine preservation.⁶ Patients with an increased risk of cervical or endometrial pathology should be counseled on the benefits of hysterectomy. Additionally, patients who have abnormal uterine bleeding from benign pathology should consider hysterectomy to treat these issues and avoid future workups (TABLE). For postmenopausal patients with recent postmenopausal bleeding, we encourage hysterectomy. A study of patients undergoing hysterectomy at the time of prolapse repair found a rate of 13% unanticipated endometrial pathology with postmenopausal bleeding and negative preoperative workup.⁷

At this time, a majority of clinicians consider the desire for future fertility to be a relative contraindication to surgical prolapse repair and advise conservative management with pessary until childbearing is complete. This is reasonable, given the paucity of safety data in subsequent pregnancies as well as the lack of prolapse outcomes after those pregnancies.^8,9 Lastly, cervical elongation is considered a relative contraindication, as it represents a risk for surgical failure.^10,11 This may be counteracted with trachelectomy at the time of hysteropexy or surgeries such as the Manchester repair, which involve a trachelectomy routinely,¹² but currently there is no strong evidence for this as routine practice.

Continue to: Uterine preservation surgical techniques and outcomes...

Uterine preservation surgical techniques and outcomes

Le Fort colpocleisis

First described in 1840 by Neugebauer of Poland and later by Le Fort in Paris in 1877, the Le Fort colpocleisis repair technique remains the most reliable prolapse surgery to date.¹⁴ The uterus is left in place while the vagina is narrowed and shortened. It typically also is performed with a levator plication to reduce the genital hiatus.

This procedure is quick and effective, with a 90% to 95% success rate. If necessary, it can be performed under local or regional anesthesia, making it a good option for medically frail patients. It is not an option for everyone, however, as penetrative intercourse is no longer an option after surgery. Studies suggest an approximately 13% dissatisfaction rate after the procedure, with most of that coming from postoperative urinary symptoms, such as urgency or stress incontinence,¹⁵ and some studies show a dissatisfaction rate as low as 0% in a well-counseled patient population.^16,17

Vaginal native tissue hysteropexy

Many patients who elect for uterine preservation at the time of prolapse surgery are “minimalists,” meaning that a vaginal native tissue procedure appeals to them due to the lack of abdominal incisions, decreased operating room time, and lack of permanent graft materials.

Of all the hysteropexy procedures, sacrospinous hysteropexy (SSHP) has the most robust data available. The approach to SSHP can be tailored to the patient’s anatomy and it is performed in a manner similar to posthysterectomy sacrospinous ligament fixation. The traditional posterior approach can be used with predominantly posterior prolapse, while an apical approach through a semilunar paracervical incision can be used for predominantly apical prolapse. Expert surgeons agree that one key to success is anchoring the suspension sutures through the cervical stroma, not just the vaginal epithelium.

Researchers in the Netherlands published the 5-year outcomes of a randomized trial that compared SSHP with vaginal hysterectomy with uterosacral ligament suspension.¹⁸ Their data showed no difference between groups in composite failure, reoperation rates, quality of life measures, and postoperative sexual function. Adverse events were very similar to those reported for posthysterectomy sacrospinous ligament fixation, including 15% transient buttock pain. Of note, the same authors explored risk factors for recurrence after SSHP and found that higher body mass index, smoking, and a large point Ba measurement were risk factors for prolapse recurrence.¹⁹

A randomized, controlled trial in the United Kingdom (the VUE trial) compared vaginal hysterectomy with apical suspension to uterine preservation with a variety of apical suspension techniques, mostly SSHP, and demonstrated no significant differences in outcomes.²⁰ Overall, SSHP is an excellent option for many patients interested in uterine preservation.

Uterosacral ligament hysteropexy (USHP), when performed vaginally, is very similar to uterosacral ligament suspension at the time of vaginal hysterectomy, with entry into the peritoneal cavity through a posterior colpotomy. The uterosacral ligaments are grasped and delayed absorbable suture placed through the ligaments and anchored into the posterior cervical stroma. Given the maintenance of the normal axis of the vagina, USHP is a good technique for patients with isolated apical defects. Unfortunately, the least amount of quality data is available for USHP at this time. Currently, evidence suggests that complications are rare and that the procedure may offer acceptable anatomic and symptomatic outcomes.²¹ Some surgeons approach the uterosacral suspension laparoscopically, which also has mixed results in the literature, with failure rates between 8% and 27% and few robust studies.^22–24

The Manchester-Fothergill operation, currently not common in the United States but popular in Europe, primarily is considered a treatment for cervical elongation when the uterosacral ligaments are intact. In this procedure, trachelectomy is performed and the uterosacral ligaments are plicated to the uterine body. Sturmdorf sutures are frequently placed to close off the endometrial canal, which can lead to hematometra and other complications of cervical stenosis. Previous unmatched studies have shown similar outcomes with the Manchester procedure compared with vaginal hysterectomy.^25,26

The largest study currently available is a registry study from Denmark, with matched cohort populations, that compared the Manchester procedure, SSHP, and total vaginal hysterectomy with uterosacral ligament suspension.²⁷ This study indicated less morbidity related to the Manchester procedure, decreased anterior recurrence compared with SSHP, and a 7% reoperation rate.²⁷ The same authors also established better cost-effectiveness with the Manchester procedure as opposed to vaginal hysterectomy with uterosacral ligament suspension.²⁸

Continue to: Vaginal mesh hysteropexy...

Hysteropexy using vaginal mesh is limited in the United States given the removal of vaginal mesh kits from the market by the US Food and Drug Administration in 2019. However, a Pelvic Floor Disorders Network randomized trial compared vaginal mesh hysteropexy using the Uphold LITE transvaginal mesh support system (Boston Scientific) and vaginal hysterectomy with uterosacral ligament suspension.²⁹ At 5 years, mesh hysteropexy had fewer failures than hysterectomy (37% vs 54%) and there was no difference in retreatment (9% vs 13%). The authors noted an 8% mesh exposure rate in the mesh hysteropexy group but 12% granulation tissue and 21% suture exposure rate in the hysterectomy group.²⁹

While vaginal mesh hysteropexy was effective in the treatment of apical prolapse, the elevated mesh exposure rate and postoperative complications ultimately led to its removal from the market.

Sacrohysteropexy

Lastly, prolapse surgery with uterine preservation may be accomplished abdominally, most commonly laparoscopically with or without robotic assistance.

Sacrohysteropexy (SHP) involves the attachment of permanent synthetic mesh posteriorly to the posterior vagina and cervix with or without the additional placement of mesh to the anterior vagina and cervix. When the anterior mesh is placed, the arms are typically routed through the broad ligament bilaterally and joined with the posterior mesh for attachment to the anterior longitudinal ligament, overlying the sacrum.

Proponents of this technique endorse the use of mesh to augment already failing native tissues and propose similarities to the durability of sacrocolpopexy. While no randomized controlled trials have compared hysterectomy with sacrocolpopexy or supracervical hysterectomy with sacrocolpopexy to sacrohysteropexy, a meta-analysis suggests that sacrohysteropexy may have a decreased risk of mesh exposure but a higher reoperation rate with lower anatomic success.⁹ Randomized trials that compared abdominal sacrohysteropexy with vaginal hysterectomy and suspension indicate that apical support may be improved with sacrohysteropexy,³⁰ but reoperations, postoperative pain and disability, and urinary dysfunction was higher with SHP.^31,32

What further research is needed?

With the increasing patient and clinician interest in uterine preservation, more research is needed to improve patient counseling and surgical planning. Much of the current research compares hysteropexy outcomes with those of traditional prolapse repairs with hysterectomy, with only a few randomized trials. We are lacking robust, prospective comparison studies between hysteropexy methods, especially vaginal native tissue techniques, long-term follow-up on the prevalence of uterine or cervical pathology after hysteropexy, and pregnancy or postpartum outcomes following uterine preservation surgery.

Currently, work is underway to validate and test the effectiveness of a questionnaire to evaluate the uterus’s importance to the patient seeking prolapse surgery in order to optimize counseling. The VUE trial, which randomizes women to vaginal hysterectomy with suspension versus various prolapse surgeries with uterine preservation, is continuing its 6-year follow-up.²⁰ In the Netherlands, an ongoing randomized, controlled trial (the SAM trial) is comparing the Manchester procedure with sacrospinous hysteropexy and will follow patients up to 24 months.³³ Fortunately, both of these trials are rigorously assessing both objective and patient-centered outcomes.

CASE Counseling helps the patient weigh surgical options

After thorough review of her surgical options, the patient elects for a uterine-preserving prolapse repair. She would like to have the most minimally invasive procedure and does not want any permanent mesh used. You suggest, and she agrees to, a sacrospinous ligament hysteropexy, as it is the current technique with the most robust data. ●

ILLUSTRATION: COPYRIGHT KIMBERLY MARTENS FOR OBG MANAGEMENT

CASE Patient desires prolapse repair

A 65-year-old postmenopausal patient (G3P3) presents to your office with symptoms of a vaginal bulge for more than 1 year. She has no urinary incontinence symptoms and no bowel dysfunction symptoms. On examination, you diagnose stage 2 uterovaginal prolapse with both anterior and apical defects. The patient declines expectant and pessary management and desires surgery, but she states that she feels her uterus “is important for me to keep, as my babies grew in there and it is part of me.” She denies any family or personal history of breast, endometrial, or ovarian cancer and has no history of abnormal cervical cancer screening or postmenopausal bleeding. What are the options for this patient?

Who is the appropriate hysteropexy patient, and how do we counsel her?

Uterine prolapse is the third leading cause of benign hysterectomy, with approximately 70,000 procedures performed each year in the United States. It has long been acknowledged that the uterus is a passive bystander to the prolapse process,¹ but modern practice often involves a hysterectomy as part of addressing apical prolapse. However, more and more uterine-preserving surgeries are being performed, with one study showing an increase from 1.8% to 5% from 2002 and 2012.²

When presented with the option to keep or remove their uterus during the time of prolapse surgery, 36% of patients indicated that they would prefer to keep their uterus with similar outcomes while 21% would still prefer uterine preservation even if outcomes were inferior compared with hysterectomy.³ Another study showed that 60% of patients would decline concurrent hysterectomy if there were equal surgical outcomes,⁴ and popular platforms, such as Health magazine (www.health.com) and AARP magazine (www.aarp.org), have listed benign hysterectomy as a “top surgery to avoid.”

Patients desire uterine preservation for many reasons, including concerns about sexual function and pleasure, the uterus being important to their sense of identity or womanhood, and concerns around menopausal symptoms. Early patient counseling and discussion of surgical goals can help clinicians fully understand a patient’s thoughts toward uterine preservation. Women who identified their uterus as important to their sense of self had a 28.2-times chance of preferring uterine preservation.³ Frequently, concerns about menopausal symptoms are more directly related to hormones and ovary removal, not uterus removal, but clinicians should be careful to also counsel patients on the increased risk of menopause in the 5 years after hysterectomy, even with ovarian preservation.⁵

There are some patients for whom experts do not recommend uterine preservation.⁶ Patients with an increased risk of cervical or endometrial pathology should be counseled on the benefits of hysterectomy. Additionally, patients who have abnormal uterine bleeding from benign pathology should consider hysterectomy to treat these issues and avoid future workups (TABLE). For postmenopausal patients with recent postmenopausal bleeding, we encourage hysterectomy. A study of patients undergoing hysterectomy at the time of prolapse repair found a rate of 13% unanticipated endometrial pathology with postmenopausal bleeding and negative preoperative workup.⁷

At this time, a majority of clinicians consider the desire for future fertility to be a relative contraindication to surgical prolapse repair and advise conservative management with pessary until childbearing is complete. This is reasonable, given the paucity of safety data in subsequent pregnancies as well as the lack of prolapse outcomes after those pregnancies.^8,9 Lastly, cervical elongation is considered a relative contraindication, as it represents a risk for surgical failure.^10,11 This may be counteracted with trachelectomy at the time of hysteropexy or surgeries such as the Manchester repair, which involve a trachelectomy routinely,¹² but currently there is no strong evidence for this as routine practice.

Continue to: Uterine preservation surgical techniques and outcomes...

Uterine preservation surgical techniques and outcomes

Le Fort colpocleisis

First described in 1840 by Neugebauer of Poland and later by Le Fort in Paris in 1877, the Le Fort colpocleisis repair technique remains the most reliable prolapse surgery to date.¹⁴ The uterus is left in place while the vagina is narrowed and shortened. It typically also is performed with a levator plication to reduce the genital hiatus.

This procedure is quick and effective, with a 90% to 95% success rate. If necessary, it can be performed under local or regional anesthesia, making it a good option for medically frail patients. It is not an option for everyone, however, as penetrative intercourse is no longer an option after surgery. Studies suggest an approximately 13% dissatisfaction rate after the procedure, with most of that coming from postoperative urinary symptoms, such as urgency or stress incontinence,¹⁵ and some studies show a dissatisfaction rate as low as 0% in a well-counseled patient population.^16,17

Vaginal native tissue hysteropexy

Many patients who elect for uterine preservation at the time of prolapse surgery are “minimalists,” meaning that a vaginal native tissue procedure appeals to them due to the lack of abdominal incisions, decreased operating room time, and lack of permanent graft materials.

Of all the hysteropexy procedures, sacrospinous hysteropexy (SSHP) has the most robust data available. The approach to SSHP can be tailored to the patient’s anatomy and it is performed in a manner similar to posthysterectomy sacrospinous ligament fixation. The traditional posterior approach can be used with predominantly posterior prolapse, while an apical approach through a semilunar paracervical incision can be used for predominantly apical prolapse. Expert surgeons agree that one key to success is anchoring the suspension sutures through the cervical stroma, not just the vaginal epithelium.

Researchers in the Netherlands published the 5-year outcomes of a randomized trial that compared SSHP with vaginal hysterectomy with uterosacral ligament suspension.¹⁸ Their data showed no difference between groups in composite failure, reoperation rates, quality of life measures, and postoperative sexual function. Adverse events were very similar to those reported for posthysterectomy sacrospinous ligament fixation, including 15% transient buttock pain. Of note, the same authors explored risk factors for recurrence after SSHP and found that higher body mass index, smoking, and a large point Ba measurement were risk factors for prolapse recurrence.¹⁹

A randomized, controlled trial in the United Kingdom (the VUE trial) compared vaginal hysterectomy with apical suspension to uterine preservation with a variety of apical suspension techniques, mostly SSHP, and demonstrated no significant differences in outcomes.²⁰ Overall, SSHP is an excellent option for many patients interested in uterine preservation.

Uterosacral ligament hysteropexy (USHP), when performed vaginally, is very similar to uterosacral ligament suspension at the time of vaginal hysterectomy, with entry into the peritoneal cavity through a posterior colpotomy. The uterosacral ligaments are grasped and delayed absorbable suture placed through the ligaments and anchored into the posterior cervical stroma. Given the maintenance of the normal axis of the vagina, USHP is a good technique for patients with isolated apical defects. Unfortunately, the least amount of quality data is available for USHP at this time. Currently, evidence suggests that complications are rare and that the procedure may offer acceptable anatomic and symptomatic outcomes.²¹ Some surgeons approach the uterosacral suspension laparoscopically, which also has mixed results in the literature, with failure rates between 8% and 27% and few robust studies.^22–24

The Manchester-Fothergill operation, currently not common in the United States but popular in Europe, primarily is considered a treatment for cervical elongation when the uterosacral ligaments are intact. In this procedure, trachelectomy is performed and the uterosacral ligaments are plicated to the uterine body. Sturmdorf sutures are frequently placed to close off the endometrial canal, which can lead to hematometra and other complications of cervical stenosis. Previous unmatched studies have shown similar outcomes with the Manchester procedure compared with vaginal hysterectomy.^25,26

The largest study currently available is a registry study from Denmark, with matched cohort populations, that compared the Manchester procedure, SSHP, and total vaginal hysterectomy with uterosacral ligament suspension.²⁷ This study indicated less morbidity related to the Manchester procedure, decreased anterior recurrence compared with SSHP, and a 7% reoperation rate.²⁷ The same authors also established better cost-effectiveness with the Manchester procedure as opposed to vaginal hysterectomy with uterosacral ligament suspension.²⁸

Continue to: Vaginal mesh hysteropexy...

Hysteropexy using vaginal mesh is limited in the United States given the removal of vaginal mesh kits from the market by the US Food and Drug Administration in 2019. However, a Pelvic Floor Disorders Network randomized trial compared vaginal mesh hysteropexy using the Uphold LITE transvaginal mesh support system (Boston Scientific) and vaginal hysterectomy with uterosacral ligament suspension.²⁹ At 5 years, mesh hysteropexy had fewer failures than hysterectomy (37% vs 54%) and there was no difference in retreatment (9% vs 13%). The authors noted an 8% mesh exposure rate in the mesh hysteropexy group but 12% granulation tissue and 21% suture exposure rate in the hysterectomy group.²⁹

While vaginal mesh hysteropexy was effective in the treatment of apical prolapse, the elevated mesh exposure rate and postoperative complications ultimately led to its removal from the market.

Sacrohysteropexy

Lastly, prolapse surgery with uterine preservation may be accomplished abdominally, most commonly laparoscopically with or without robotic assistance.

Sacrohysteropexy (SHP) involves the attachment of permanent synthetic mesh posteriorly to the posterior vagina and cervix with or without the additional placement of mesh to the anterior vagina and cervix. When the anterior mesh is placed, the arms are typically routed through the broad ligament bilaterally and joined with the posterior mesh for attachment to the anterior longitudinal ligament, overlying the sacrum.

Proponents of this technique endorse the use of mesh to augment already failing native tissues and propose similarities to the durability of sacrocolpopexy. While no randomized controlled trials have compared hysterectomy with sacrocolpopexy or supracervical hysterectomy with sacrocolpopexy to sacrohysteropexy, a meta-analysis suggests that sacrohysteropexy may have a decreased risk of mesh exposure but a higher reoperation rate with lower anatomic success.⁹ Randomized trials that compared abdominal sacrohysteropexy with vaginal hysterectomy and suspension indicate that apical support may be improved with sacrohysteropexy,³⁰ but reoperations, postoperative pain and disability, and urinary dysfunction was higher with SHP.^31,32

What further research is needed?

With the increasing patient and clinician interest in uterine preservation, more research is needed to improve patient counseling and surgical planning. Much of the current research compares hysteropexy outcomes with those of traditional prolapse repairs with hysterectomy, with only a few randomized trials. We are lacking robust, prospective comparison studies between hysteropexy methods, especially vaginal native tissue techniques, long-term follow-up on the prevalence of uterine or cervical pathology after hysteropexy, and pregnancy or postpartum outcomes following uterine preservation surgery.

Currently, work is underway to validate and test the effectiveness of a questionnaire to evaluate the uterus’s importance to the patient seeking prolapse surgery in order to optimize counseling. The VUE trial, which randomizes women to vaginal hysterectomy with suspension versus various prolapse surgeries with uterine preservation, is continuing its 6-year follow-up.²⁰ In the Netherlands, an ongoing randomized, controlled trial (the SAM trial) is comparing the Manchester procedure with sacrospinous hysteropexy and will follow patients up to 24 months.³³ Fortunately, both of these trials are rigorously assessing both objective and patient-centered outcomes.

CASE Counseling helps the patient weigh surgical options

After thorough review of her surgical options, the patient elects for a uterine-preserving prolapse repair. She would like to have the most minimally invasive procedure and does not want any permanent mesh used. You suggest, and she agrees to, a sacrospinous ligament hysteropexy, as it is the current technique with the most robust data. ●