Vials of drug

A phase 2 study of the antibody BI-505 in patients with multiple myeloma (MM) has been placed on full clinical hold.

BioInvent International, the company developing BI-505, said it has received verbal notice of the clinical hold from the US Food and Drug Administration (FDA).

The clinical hold means no new subjects can be enrolled on the trial, and there can be no further dosing of subjects who are already enrolled.

BioInvent International said it has yet to receive written notice of the clinical hold from the FDA. However, based on verbal communications, the clinical hold is due to an adverse cardiopulmonary event.

The study (NCT02756728) is being conducted by BioInvent International in collaboration with investigators at the University of Pennsylvania.

The goal of the study is to determine if BI-505 can deepen therapeutic response and thereby prevent or delay relapse in MM patients undergoing autologous stem cell transplant with high-dose melphalan.

BioInvent International said it will analyze the possibility to obtain release of the clinical hold and will provide updates when there is further information to report.

About BI-505

BI-505 is a human antibody targeting ICAM-1, a protein that is elevated in MM cells. BI-505 has been shown to attack MM in 2 ways—by inducing apoptosis in MM cells and by engaging macrophages to attack and kill MM cells.

According to BioInvent International, the development strategy for BI-505 is focused on eliminating residual disease by combining the antibody with modern standard-of-care drugs used to treat MM.

The company said BI-505 proved safe in a phase 1 trial of patients with relapsed/refractory MM, as well as demonstrating “signs of a positive effect against the disease.” This study was published in Clinical Cancer Research in June 2015.

BI-505 has received orphan drug designation as a treatment for MM from both the FDA and the European Medicines Agency.

Vials of drug

A phase 2 study of the antibody BI-505 in patients with multiple myeloma (MM) has been placed on full clinical hold.

BioInvent International, the company developing BI-505, said it has received verbal notice of the clinical hold from the US Food and Drug Administration (FDA).

The clinical hold means no new subjects can be enrolled on the trial, and there can be no further dosing of subjects who are already enrolled.

BioInvent International said it has yet to receive written notice of the clinical hold from the FDA. However, based on verbal communications, the clinical hold is due to an adverse cardiopulmonary event.

The study (NCT02756728) is being conducted by BioInvent International in collaboration with investigators at the University of Pennsylvania.

The goal of the study is to determine if BI-505 can deepen therapeutic response and thereby prevent or delay relapse in MM patients undergoing autologous stem cell transplant with high-dose melphalan.

BioInvent International said it will analyze the possibility to obtain release of the clinical hold and will provide updates when there is further information to report.

About BI-505

BI-505 is a human antibody targeting ICAM-1, a protein that is elevated in MM cells. BI-505 has been shown to attack MM in 2 ways—by inducing apoptosis in MM cells and by engaging macrophages to attack and kill MM cells.

According to BioInvent International, the development strategy for BI-505 is focused on eliminating residual disease by combining the antibody with modern standard-of-care drugs used to treat MM.

The company said BI-505 proved safe in a phase 1 trial of patients with relapsed/refractory MM, as well as demonstrating “signs of a positive effect against the disease.” This study was published in Clinical Cancer Research in June 2015.

BI-505 has received orphan drug designation as a treatment for MM from both the FDA and the European Medicines Agency.

Vials of drug

A phase 2 study of the antibody BI-505 in patients with multiple myeloma (MM) has been placed on full clinical hold.

BioInvent International, the company developing BI-505, said it has received verbal notice of the clinical hold from the US Food and Drug Administration (FDA).

The clinical hold means no new subjects can be enrolled on the trial, and there can be no further dosing of subjects who are already enrolled.

BioInvent International said it has yet to receive written notice of the clinical hold from the FDA. However, based on verbal communications, the clinical hold is due to an adverse cardiopulmonary event.

The study (NCT02756728) is being conducted by BioInvent International in collaboration with investigators at the University of Pennsylvania.

The goal of the study is to determine if BI-505 can deepen therapeutic response and thereby prevent or delay relapse in MM patients undergoing autologous stem cell transplant with high-dose melphalan.

BioInvent International said it will analyze the possibility to obtain release of the clinical hold and will provide updates when there is further information to report.

About BI-505

BI-505 is a human antibody targeting ICAM-1, a protein that is elevated in MM cells. BI-505 has been shown to attack MM in 2 ways—by inducing apoptosis in MM cells and by engaging macrophages to attack and kill MM cells.

According to BioInvent International, the development strategy for BI-505 is focused on eliminating residual disease by combining the antibody with modern standard-of-care drugs used to treat MM.

The company said BI-505 proved safe in a phase 1 trial of patients with relapsed/refractory MM, as well as demonstrating “signs of a positive effect against the disease.” This study was published in Clinical Cancer Research in June 2015.

BI-505 has received orphan drug designation as a treatment for MM from both the FDA and the European Medicines Agency.

Panobinostat (Farydak)

Photo courtesy of Novartis

Researchers say they have identified a high-risk subtype of acute lymphoblastic leukemia (ALL) that may respond to treatment with the histone deacetylase (HDAC) inhibitor panobinostat.

The ALL subtype is characterized by chromosomal rearrangements that involve the MEF2D gene and 1 of 6 partner genes, most often BCL9.

The researchers described this subtype, known as MEF2D-rearranged ALL, in Nature Communications.

“MEF2D is a transcription factor that switches on expression of other genes during normal development,” said study author Charles Mullighan, MD, MBBS, of the St. Jude Children’s Research Hospital in Memphis, Tennessee.

“We found that MEF2D chromosomal rearrangements disrupt expression of those genes and create a vulnerability to at least one targeted therapy, the drug panobinostat.”

Dr Mullighan and his colleagues performed genomic analyses on samples from a total of 1724 children, adolescents, and adults with ALL. This revealed 52 patients with MEF2D rearrangements.

MEF2D-rearranged ALL

The researchers calculated that MEF2D-rearranged ALL accounted for 5.3% of the ALL cases whose genetic basis was unknown.

The team also noted that MEF2D-rearranged ALL occurred most frequently in adolescents. Although, overall, ALL occurs most often in children between 3 and 5 years old, the average patient with MEF2D-rearranged ALL was 14.

In addition, MEF2D-rearranged ALL was associated with reduced survival when compared to some other ALL subtypes. The 5-year cancer-free survival for MEF2D-rearranged ALL patients was 71.6%.

The researchers also found that a fusion protein resulting from the MEF2D rearrangement led to sustained growth of mouse cells when compared to wild-type MEF2D or other proteins.

“That indicates the MEF2D fusion is a key step in transforming a normal white blood cell with a finite lifespan into a leukemic cell that is immortal,” Dr Mullighan said.

Role for panobinostat

MEF2D-rearranged leukemic cells produced high levels of HDAC9, which is targeted by panobinostat.

The researchers tested panobinostat in the lab and found the drug stopped proliferation of human MEF2D-rearranged leukemic cells.

Dr Mullighan said MEF2D-rearranged leukemic cells were exquisitely sensitive to panobinostat, which suggested the drug might function in a more targeted manner against cells with the rearrangement.

“If further testing of panobinostat, either alone or in combination therapy, confirms the anti-proliferative activity, that would lay the foundation for a clinical trial in patients, particularly patients with high-risk disease or those who have relapsed,” he said. 

Panobinostat (Farydak)

Photo courtesy of Novartis

Researchers say they have identified a high-risk subtype of acute lymphoblastic leukemia (ALL) that may respond to treatment with the histone deacetylase (HDAC) inhibitor panobinostat.

The ALL subtype is characterized by chromosomal rearrangements that involve the MEF2D gene and 1 of 6 partner genes, most often BCL9.

The researchers described this subtype, known as MEF2D-rearranged ALL, in Nature Communications.

“MEF2D is a transcription factor that switches on expression of other genes during normal development,” said study author Charles Mullighan, MD, MBBS, of the St. Jude Children’s Research Hospital in Memphis, Tennessee.

“We found that MEF2D chromosomal rearrangements disrupt expression of those genes and create a vulnerability to at least one targeted therapy, the drug panobinostat.”

Dr Mullighan and his colleagues performed genomic analyses on samples from a total of 1724 children, adolescents, and adults with ALL. This revealed 52 patients with MEF2D rearrangements.

MEF2D-rearranged ALL

The researchers calculated that MEF2D-rearranged ALL accounted for 5.3% of the ALL cases whose genetic basis was unknown.

The team also noted that MEF2D-rearranged ALL occurred most frequently in adolescents. Although, overall, ALL occurs most often in children between 3 and 5 years old, the average patient with MEF2D-rearranged ALL was 14.

In addition, MEF2D-rearranged ALL was associated with reduced survival when compared to some other ALL subtypes. The 5-year cancer-free survival for MEF2D-rearranged ALL patients was 71.6%.

The researchers also found that a fusion protein resulting from the MEF2D rearrangement led to sustained growth of mouse cells when compared to wild-type MEF2D or other proteins.

“That indicates the MEF2D fusion is a key step in transforming a normal white blood cell with a finite lifespan into a leukemic cell that is immortal,” Dr Mullighan said.

Role for panobinostat

MEF2D-rearranged leukemic cells produced high levels of HDAC9, which is targeted by panobinostat.

The researchers tested panobinostat in the lab and found the drug stopped proliferation of human MEF2D-rearranged leukemic cells.

Dr Mullighan said MEF2D-rearranged leukemic cells were exquisitely sensitive to panobinostat, which suggested the drug might function in a more targeted manner against cells with the rearrangement.

“If further testing of panobinostat, either alone or in combination therapy, confirms the anti-proliferative activity, that would lay the foundation for a clinical trial in patients, particularly patients with high-risk disease or those who have relapsed,” he said. 

Panobinostat (Farydak)

Photo courtesy of Novartis

Researchers say they have identified a high-risk subtype of acute lymphoblastic leukemia (ALL) that may respond to treatment with the histone deacetylase (HDAC) inhibitor panobinostat.

The ALL subtype is characterized by chromosomal rearrangements that involve the MEF2D gene and 1 of 6 partner genes, most often BCL9.

The researchers described this subtype, known as MEF2D-rearranged ALL, in Nature Communications.

“MEF2D is a transcription factor that switches on expression of other genes during normal development,” said study author Charles Mullighan, MD, MBBS, of the St. Jude Children’s Research Hospital in Memphis, Tennessee.

“We found that MEF2D chromosomal rearrangements disrupt expression of those genes and create a vulnerability to at least one targeted therapy, the drug panobinostat.”

Dr Mullighan and his colleagues performed genomic analyses on samples from a total of 1724 children, adolescents, and adults with ALL. This revealed 52 patients with MEF2D rearrangements.

MEF2D-rearranged ALL

The researchers calculated that MEF2D-rearranged ALL accounted for 5.3% of the ALL cases whose genetic basis was unknown.

The team also noted that MEF2D-rearranged ALL occurred most frequently in adolescents. Although, overall, ALL occurs most often in children between 3 and 5 years old, the average patient with MEF2D-rearranged ALL was 14.

In addition, MEF2D-rearranged ALL was associated with reduced survival when compared to some other ALL subtypes. The 5-year cancer-free survival for MEF2D-rearranged ALL patients was 71.6%.

The researchers also found that a fusion protein resulting from the MEF2D rearrangement led to sustained growth of mouse cells when compared to wild-type MEF2D or other proteins.

“That indicates the MEF2D fusion is a key step in transforming a normal white blood cell with a finite lifespan into a leukemic cell that is immortal,” Dr Mullighan said.

Role for panobinostat

MEF2D-rearranged leukemic cells produced high levels of HDAC9, which is targeted by panobinostat.

The researchers tested panobinostat in the lab and found the drug stopped proliferation of human MEF2D-rearranged leukemic cells.

Dr Mullighan said MEF2D-rearranged leukemic cells were exquisitely sensitive to panobinostat, which suggested the drug might function in a more targeted manner against cells with the rearrangement.

“If further testing of panobinostat, either alone or in combination therapy, confirms the anti-proliferative activity, that would lay the foundation for a clinical trial in patients, particularly patients with high-risk disease or those who have relapsed,” he said. 

IN THIS ARTICLE

• Clinical presentation
• Disease triggers
• Outcome for the case patient

A 4-month-old white boy is brought to the allergy office for evaluation of a lesion on his back, first noticed when he was one month old. His parents report that on two separate occasions he developed a bright red, whole-body rash that resolved on its own. He is described as a “fussy” baby who has been on both milk- and soy-based formulas. Aside from mild eczema and infantile seborrheic ­dermatitis, his medical history is unremarkable.

Physical examination reveals a reddish, 3-cm plaque on his left upper back that, when stroked, exhibits an immediate urticarial response. The patient is given cetirizine in the office and within 45 minutes, the flushing resolves. A normal tryptase level is obtained. The patient is diagnosed with a solitary mastocytoma.

DISCUSSION

Mast cells play a central role in allergic rhinitis, asthma, eczema, and anaphylaxis; they are also a vital component in the inflammatory process. Cutaneous mastocytosis is a pathologic increase in mast cells that, when degranulated, release histamine and tryptase.¹ Histamine is produced equally by both mast cells and basophils, while the production of tryptase is relatively specific to mast cells. An elevated tryptase level is indicative of mast cell activation. The signs and symptoms associated with cutaneous mastocytosis are due to the release of these ­mediators.²

While there is no gender bias for cutaneous mastocytosis, there is a bimodal distribution: Children from birth to age 2 account for 55% of cases, whereas 35% of cases occur in those older than 15—the remaining 10% are between these ages.¹ During the first year of life, 60% to 80% of patients with cutaneous mastocytosis will develop lesions. Familial cases are rare.²

Clinical presentation

The presentation of cutaneous mastocytosis can vary. It is often mistaken for common childhood rashes such as poison ivy, eczema, or hives. The effects of histamine and tryptase cause children to present with pruritus, flushing, and headache. Gastrointestinal symptoms, such as abdominal pain and diarrhea, can also occur as a result of histamine release. Symptoms can occur spontaneously or be induced by certain triggers (see Table).³

There are three types of cutaneous mastocytosis: urticarial pigmentosa (UP), solitary mastocytoma, and diffuse cutaneous mastocytosis (DCM). UP is the most common, representing 70% to 90% of all cases.³ It typically manifests as multiple red, brown, or yellow lesions that are small (usually < 2 cm). A positive Darier sign (the formation of a wheal and flare after stroking one or several lesions) is common in these patients.^2,3

Solitary mastocytomas are single, indurated, red-brown macules, papules, or plaques.⁴ Frequently seen on the trunk, extremities, head, or neck, these lesions resemble UP but are larger (up to several centimeters in diameter).^2,4 A positive Darier sign is elicited in approximately 50% of these patients.⁴ Solitary mastocytomas are seen in 10% to 15% of children with cutaneous mastocytosis.⁴

DCM accounts for only 1% to 3% of cases and typically involves the entire skin, which is usually thick, with a normal or yellowish brown color.³ Affected patients may experience blistering and bullae. Severe symptoms, including whole-body flushing, pruritus, diarrhea, intestinal bleeding, hypotension, anemia, and hypovolemic shock, can occur; deaths have been reported.²

Following a thorough history and physical exam, the diagnosis of cutaneous mastocytosis can be made based on clinical findings.⁵ It can be confirmed by a punch biopsy of the lesion and measurement of serum tryptase levels; higher levels have been shown to correlate to the number of mast cells in the skin and the child’s cutaneous disease burden.^2,4 Ordering baseline tryptase levels can also help distinguish children at risk for severe episodes of mast cell activation from those who may just have a mild case.⁶

If the patient exhibits symptoms suggestive of systemic mastocytosis (an abnormal increase in mast cells in extracutaneous organs, including bone marrow) or there is suspicion for malignancy, efforts must be made to rule out these more serious diagnoses. A complete white blood cell count with differential, metabolic profile with liver enzymes, and sedimentation rate should be obtained.⁴

Treatment

The treatment of cutaneous mastocytosis is symptomatic, as it is typically a benign disease. The goal of therapy is to prevent mast cell activation, and hence the symptoms that occur when mast cells release their mediators, by avoiding obvious triggers.⁴

NSAIDs have been reported to cause mast cell mediator release and should therefore be avoided. Since extremes in temperature—particularly heat—can lead to mast cell activation, it is important to control the temperature of a bath or swimming pool and to be wary of exposure to air conditioning. Though easier said than done, soothing crying babies and children is also helpful, as irritability is a known trigger. Management of anxiety and avoidance of stress when possible is recommended.²

Treatment usually begins with H₁ and H₂ blockers. Cetirizine and diphenhydramine work to control the itching, while ranitidine and famotidine help manage gastric acid secretion when there are symptoms of abdominal pain and peptic ulcer disease.³ Hydroxyzine is effective in controlling both itch and gastric acid secretion.⁴ Water-soluble cromolyn sodium cream helps to decrease the itch and flare of a mastocytoma; the oral form is also effective.³ Another option to relieve itching is to apply topical corticosteroids with an occlusive dressing.

An epinephrine auto-injector is recommended due to the risk for anaphylaxis; this risk, however, has not been clearly established in cutaneous mastocytosis, specifically in DCM. During an acute and severe flare that induces hypotension, wheezing, and/or laryngeal edema, epinephrine should be administered while the child is lying down.^3,4

Surgical excision can be considered when other treatment options fail, or if the lesion is located on the scalp, flexure area, palm, or sole.^3,4

Prognosis

The prognosis for a child with a solitary mastocytoma is extremely good. By the time the child reaches puberty, there is typically spontaneous regression.

If any type of mastocytoma persists beyond adolescence, or tryptase levels continue to rise after puberty, however, that raises concern for progression to systemic mastocytosis. Although this diagnosis is rare in children, bone marrow studies may be necessary to determine the patient’s course.¹

OUTCOME FOR THE CASE PATIENT

The patient was placed on daily cetirizine. His parents were advised not to irritate the lesion and were educated on possible triggers, including the need to avoid NSAIDs. They were also trained in the use of an epinephrine auto-injector.

CONCLUSION

Cutaneous mastocytosis should be included in the differential diagnosis of rashes and skin lesions in pediatric patients. It is important to be able to recognize the presenting signs and symptoms of a mastocytoma and to monitor the lesion over time.⁴ Educating the child’s parents, teachers, and caregivers about potential triggers and treatment of a mast cell activation attack can help minimize the symptoms.

IN THIS ARTICLE

• Clinical presentation
• Disease triggers
• Outcome for the case patient

A 4-month-old white boy is brought to the allergy office for evaluation of a lesion on his back, first noticed when he was one month old. His parents report that on two separate occasions he developed a bright red, whole-body rash that resolved on its own. He is described as a “fussy” baby who has been on both milk- and soy-based formulas. Aside from mild eczema and infantile seborrheic ­dermatitis, his medical history is unremarkable.

Physical examination reveals a reddish, 3-cm plaque on his left upper back that, when stroked, exhibits an immediate urticarial response. The patient is given cetirizine in the office and within 45 minutes, the flushing resolves. A normal tryptase level is obtained. The patient is diagnosed with a solitary mastocytoma.

DISCUSSION

Mast cells play a central role in allergic rhinitis, asthma, eczema, and anaphylaxis; they are also a vital component in the inflammatory process. Cutaneous mastocytosis is a pathologic increase in mast cells that, when degranulated, release histamine and tryptase.¹ Histamine is produced equally by both mast cells and basophils, while the production of tryptase is relatively specific to mast cells. An elevated tryptase level is indicative of mast cell activation. The signs and symptoms associated with cutaneous mastocytosis are due to the release of these ­mediators.²

While there is no gender bias for cutaneous mastocytosis, there is a bimodal distribution: Children from birth to age 2 account for 55% of cases, whereas 35% of cases occur in those older than 15—the remaining 10% are between these ages.¹ During the first year of life, 60% to 80% of patients with cutaneous mastocytosis will develop lesions. Familial cases are rare.²

Clinical presentation

The presentation of cutaneous mastocytosis can vary. It is often mistaken for common childhood rashes such as poison ivy, eczema, or hives. The effects of histamine and tryptase cause children to present with pruritus, flushing, and headache. Gastrointestinal symptoms, such as abdominal pain and diarrhea, can also occur as a result of histamine release. Symptoms can occur spontaneously or be induced by certain triggers (see Table).³

There are three types of cutaneous mastocytosis: urticarial pigmentosa (UP), solitary mastocytoma, and diffuse cutaneous mastocytosis (DCM). UP is the most common, representing 70% to 90% of all cases.³ It typically manifests as multiple red, brown, or yellow lesions that are small (usually < 2 cm). A positive Darier sign (the formation of a wheal and flare after stroking one or several lesions) is common in these patients.^2,3

Solitary mastocytomas are single, indurated, red-brown macules, papules, or plaques.⁴ Frequently seen on the trunk, extremities, head, or neck, these lesions resemble UP but are larger (up to several centimeters in diameter).^2,4 A positive Darier sign is elicited in approximately 50% of these patients.⁴ Solitary mastocytomas are seen in 10% to 15% of children with cutaneous mastocytosis.⁴

DCM accounts for only 1% to 3% of cases and typically involves the entire skin, which is usually thick, with a normal or yellowish brown color.³ Affected patients may experience blistering and bullae. Severe symptoms, including whole-body flushing, pruritus, diarrhea, intestinal bleeding, hypotension, anemia, and hypovolemic shock, can occur; deaths have been reported.²

Following a thorough history and physical exam, the diagnosis of cutaneous mastocytosis can be made based on clinical findings.⁵ It can be confirmed by a punch biopsy of the lesion and measurement of serum tryptase levels; higher levels have been shown to correlate to the number of mast cells in the skin and the child’s cutaneous disease burden.^2,4 Ordering baseline tryptase levels can also help distinguish children at risk for severe episodes of mast cell activation from those who may just have a mild case.⁶

If the patient exhibits symptoms suggestive of systemic mastocytosis (an abnormal increase in mast cells in extracutaneous organs, including bone marrow) or there is suspicion for malignancy, efforts must be made to rule out these more serious diagnoses. A complete white blood cell count with differential, metabolic profile with liver enzymes, and sedimentation rate should be obtained.⁴

Treatment

The treatment of cutaneous mastocytosis is symptomatic, as it is typically a benign disease. The goal of therapy is to prevent mast cell activation, and hence the symptoms that occur when mast cells release their mediators, by avoiding obvious triggers.⁴

NSAIDs have been reported to cause mast cell mediator release and should therefore be avoided. Since extremes in temperature—particularly heat—can lead to mast cell activation, it is important to control the temperature of a bath or swimming pool and to be wary of exposure to air conditioning. Though easier said than done, soothing crying babies and children is also helpful, as irritability is a known trigger. Management of anxiety and avoidance of stress when possible is recommended.²

Treatment usually begins with H₁ and H₂ blockers. Cetirizine and diphenhydramine work to control the itching, while ranitidine and famotidine help manage gastric acid secretion when there are symptoms of abdominal pain and peptic ulcer disease.³ Hydroxyzine is effective in controlling both itch and gastric acid secretion.⁴ Water-soluble cromolyn sodium cream helps to decrease the itch and flare of a mastocytoma; the oral form is also effective.³ Another option to relieve itching is to apply topical corticosteroids with an occlusive dressing.

An epinephrine auto-injector is recommended due to the risk for anaphylaxis; this risk, however, has not been clearly established in cutaneous mastocytosis, specifically in DCM. During an acute and severe flare that induces hypotension, wheezing, and/or laryngeal edema, epinephrine should be administered while the child is lying down.^3,4

Surgical excision can be considered when other treatment options fail, or if the lesion is located on the scalp, flexure area, palm, or sole.^3,4

Prognosis

The prognosis for a child with a solitary mastocytoma is extremely good. By the time the child reaches puberty, there is typically spontaneous regression.

If any type of mastocytoma persists beyond adolescence, or tryptase levels continue to rise after puberty, however, that raises concern for progression to systemic mastocytosis. Although this diagnosis is rare in children, bone marrow studies may be necessary to determine the patient’s course.¹

OUTCOME FOR THE CASE PATIENT

The patient was placed on daily cetirizine. His parents were advised not to irritate the lesion and were educated on possible triggers, including the need to avoid NSAIDs. They were also trained in the use of an epinephrine auto-injector.

CONCLUSION

Cutaneous mastocytosis should be included in the differential diagnosis of rashes and skin lesions in pediatric patients. It is important to be able to recognize the presenting signs and symptoms of a mastocytoma and to monitor the lesion over time.⁴ Educating the child’s parents, teachers, and caregivers about potential triggers and treatment of a mast cell activation attack can help minimize the symptoms.

IN THIS ARTICLE

• Clinical presentation
• Disease triggers
• Outcome for the case patient

A 4-month-old white boy is brought to the allergy office for evaluation of a lesion on his back, first noticed when he was one month old. His parents report that on two separate occasions he developed a bright red, whole-body rash that resolved on its own. He is described as a “fussy” baby who has been on both milk- and soy-based formulas. Aside from mild eczema and infantile seborrheic ­dermatitis, his medical history is unremarkable.

Physical examination reveals a reddish, 3-cm plaque on his left upper back that, when stroked, exhibits an immediate urticarial response. The patient is given cetirizine in the office and within 45 minutes, the flushing resolves. A normal tryptase level is obtained. The patient is diagnosed with a solitary mastocytoma.

DISCUSSION

Mast cells play a central role in allergic rhinitis, asthma, eczema, and anaphylaxis; they are also a vital component in the inflammatory process. Cutaneous mastocytosis is a pathologic increase in mast cells that, when degranulated, release histamine and tryptase.¹ Histamine is produced equally by both mast cells and basophils, while the production of tryptase is relatively specific to mast cells. An elevated tryptase level is indicative of mast cell activation. The signs and symptoms associated with cutaneous mastocytosis are due to the release of these ­mediators.²

While there is no gender bias for cutaneous mastocytosis, there is a bimodal distribution: Children from birth to age 2 account for 55% of cases, whereas 35% of cases occur in those older than 15—the remaining 10% are between these ages.¹ During the first year of life, 60% to 80% of patients with cutaneous mastocytosis will develop lesions. Familial cases are rare.²

Clinical presentation

The presentation of cutaneous mastocytosis can vary. It is often mistaken for common childhood rashes such as poison ivy, eczema, or hives. The effects of histamine and tryptase cause children to present with pruritus, flushing, and headache. Gastrointestinal symptoms, such as abdominal pain and diarrhea, can also occur as a result of histamine release. Symptoms can occur spontaneously or be induced by certain triggers (see Table).³

There are three types of cutaneous mastocytosis: urticarial pigmentosa (UP), solitary mastocytoma, and diffuse cutaneous mastocytosis (DCM). UP is the most common, representing 70% to 90% of all cases.³ It typically manifests as multiple red, brown, or yellow lesions that are small (usually < 2 cm). A positive Darier sign (the formation of a wheal and flare after stroking one or several lesions) is common in these patients.^2,3

Solitary mastocytomas are single, indurated, red-brown macules, papules, or plaques.⁴ Frequently seen on the trunk, extremities, head, or neck, these lesions resemble UP but are larger (up to several centimeters in diameter).^2,4 A positive Darier sign is elicited in approximately 50% of these patients.⁴ Solitary mastocytomas are seen in 10% to 15% of children with cutaneous mastocytosis.⁴

DCM accounts for only 1% to 3% of cases and typically involves the entire skin, which is usually thick, with a normal or yellowish brown color.³ Affected patients may experience blistering and bullae. Severe symptoms, including whole-body flushing, pruritus, diarrhea, intestinal bleeding, hypotension, anemia, and hypovolemic shock, can occur; deaths have been reported.²

Following a thorough history and physical exam, the diagnosis of cutaneous mastocytosis can be made based on clinical findings.⁵ It can be confirmed by a punch biopsy of the lesion and measurement of serum tryptase levels; higher levels have been shown to correlate to the number of mast cells in the skin and the child’s cutaneous disease burden.^2,4 Ordering baseline tryptase levels can also help distinguish children at risk for severe episodes of mast cell activation from those who may just have a mild case.⁶

If the patient exhibits symptoms suggestive of systemic mastocytosis (an abnormal increase in mast cells in extracutaneous organs, including bone marrow) or there is suspicion for malignancy, efforts must be made to rule out these more serious diagnoses. A complete white blood cell count with differential, metabolic profile with liver enzymes, and sedimentation rate should be obtained.⁴

Treatment

The treatment of cutaneous mastocytosis is symptomatic, as it is typically a benign disease. The goal of therapy is to prevent mast cell activation, and hence the symptoms that occur when mast cells release their mediators, by avoiding obvious triggers.⁴

NSAIDs have been reported to cause mast cell mediator release and should therefore be avoided. Since extremes in temperature—particularly heat—can lead to mast cell activation, it is important to control the temperature of a bath or swimming pool and to be wary of exposure to air conditioning. Though easier said than done, soothing crying babies and children is also helpful, as irritability is a known trigger. Management of anxiety and avoidance of stress when possible is recommended.²

Treatment usually begins with H₁ and H₂ blockers. Cetirizine and diphenhydramine work to control the itching, while ranitidine and famotidine help manage gastric acid secretion when there are symptoms of abdominal pain and peptic ulcer disease.³ Hydroxyzine is effective in controlling both itch and gastric acid secretion.⁴ Water-soluble cromolyn sodium cream helps to decrease the itch and flare of a mastocytoma; the oral form is also effective.³ Another option to relieve itching is to apply topical corticosteroids with an occlusive dressing.

An epinephrine auto-injector is recommended due to the risk for anaphylaxis; this risk, however, has not been clearly established in cutaneous mastocytosis, specifically in DCM. During an acute and severe flare that induces hypotension, wheezing, and/or laryngeal edema, epinephrine should be administered while the child is lying down.^3,4

Surgical excision can be considered when other treatment options fail, or if the lesion is located on the scalp, flexure area, palm, or sole.^3,4

Prognosis

The prognosis for a child with a solitary mastocytoma is extremely good. By the time the child reaches puberty, there is typically spontaneous regression.

If any type of mastocytoma persists beyond adolescence, or tryptase levels continue to rise after puberty, however, that raises concern for progression to systemic mastocytosis. Although this diagnosis is rare in children, bone marrow studies may be necessary to determine the patient’s course.¹

OUTCOME FOR THE CASE PATIENT

The patient was placed on daily cetirizine. His parents were advised not to irritate the lesion and were educated on possible triggers, including the need to avoid NSAIDs. They were also trained in the use of an epinephrine auto-injector.

CONCLUSION

Cutaneous mastocytosis should be included in the differential diagnosis of rashes and skin lesions in pediatric patients. It is important to be able to recognize the presenting signs and symptoms of a mastocytoma and to monitor the lesion over time.⁴ Educating the child’s parents, teachers, and caregivers about potential triggers and treatment of a mast cell activation attack can help minimize the symptoms.

The antidiabetic drugs that have recently shown efficacy for reducing cardiovascular-disease events in patients with type 2 diabetes have prompted some cardiologists to start acting a bit more like diabetologists.

The dramatic reduction in cardiovascular death and heart failure hospitalization seen during treatment with empagliflozin (Jardiance) in the EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial, for example, has prompted some cardiologists in the year since the first EMPA-REG report to become active prescribers of the drug to their patients who have type 2 diabetes and cardiovascular disease. The same evidence has driven other cardiologists who may not feel fully comfortable prescribing an antidiabetic drug on their own to enter into active partnerships with endocrinologists to work as a team to put diabetes patients with cardiovascular disease on empagliflozin.

Mitchel L. Zoler/Frontline Medical News

In Dr. Fitchett’s practice, “if a patient with type 2 diabetes has an endocrinologist, then I will send a letter to that physician saying I think the patient should be on one of these drugs,” empagliflozin or liraglutide, he said. “If the patient is being treated by a primary care physician, then I will prescribe empagliflozin myself because most primary care physicians are not willing to prescribe it. I think more and more cardiologists are doing this. The great thing about empagliflozin and liraglutide is that they do not cause hypoglycemia and the adverse effect profiles are relatively good. As long as drug cost is not an issue, then as cardiologists we need to adjust glycemia control with cardiovascular benefit as we did years ago with statin treatment,” explained Dr. Fitchett, a cardiologist at St. Michael’s Hospital in Toronto and a senior collaborator and coauthor on the EMPA-REG study.

When results from the 4S [Scandinavian Simvastatin Survival Study] came out in 1994, proving that long-term statin treatment was both safe and increased survival in patients with coronary heart disease, “cardiologists took over lipid management from endocrinologists,” he recalled. “We now have a safe and simple treatment for glucose lowering that also cuts cardiovascular disease events, so cardiologists have to also be involved, at least to some extent. Their degree of involvement depends on their practice and who provides a patient’s primary diabetes care,” he said.

Cardiologists vary on empagliflozin

Other cardiologists are mixed in their take on personally prescribing antidiabetic drugs to high-risk patients with type 2 diabetes. Greg C. Fonarow, MD, has also aggressively taken to empagliflozin over the past year, especially for his patients with heart failure or at high risk for developing heart failure. The EMPA-REG results showed that empagliflozin’s potent impact on reducing cardiovascular death in patients linked closely with a reduction in heart failure hospitalizations. In his recent experience, endocrinologists as well as other physicians who care for patients with type 2 diabetes “are often reluctant to make any changes [in a patient’s hypoglycemic regimen], and in general they have not gravitated toward the treatments that have been shown to improve cardiovascular outcomes and instead focus solely on a patient’s hemoglobin A_1c,” Dr. Fonarow said in an interview at the recent annual meeting of the Heart Failure Society of America.

Mitchel L. Zoler/Frontline Medical News

He said he prescribes empagliflozin to patients with type 2 diabetes if they are hospitalized for heart failure or as outpatients, and he targets it to patients diagnosed with heart failure – including heart failure with preserved ejection fraction – as well as to patients with other forms of cardiovascular disease, closely following the EMPA-REG enrollment criteria. It’s too early in the experience with empagliflozin to use it preferentially in diabetes patients without cardiovascular disease or patients who in any other way fall outside the enrollment criteria for EMPA-REG, he said.

“I am happy to consult with their endocrinologist, or I tell patients to discuss this treatment with their endocrinologist. If the endocrinologist prescribes empagliflozin, great; if not, I feel an obligation to provide the best care I can to my patients. This is not a hard medication to use. The safety profile is good. Treatment with empagliflozin obviously has renal-function considerations, but that’s true for many drugs. The biggest challenge is what is covered by the patient’s insurance. We often need preauthorization.

“So far I have seen excellent responses in patients for both metabolic control and clinical responses in patients with heart failure. Their symptoms seem to improve,” said Dr. Fonarow, professor of medicine and co-chief of cardiology at the University of Southern California , Los Angeles.

While Dr. Fonarow cautioned that he also would not start empagliflozin in a patient with a HbA_1c below 7%, he would seriously consider swapping out a patient’s drug for empagliflozin if it were a sulfonylurea or a dipeptidyl peptidase-4 inhibitor. He stopped short of suggesting a substitution of empagliflozin for metformin. In Dr. Fonarow’s opinion, the evidence for empagliflozin is also “more robust” than it has been for liraglutide or semaglutide. With what’s now known about the clinical impact of these drugs, he foresees a time when a combination between a SGLT-2 inhibitor, with its effect on heart failure, and a GLP-1 analogue, with its effect on atherosclerotic disease, may seem an ideal initial drug pairing for patients with type 2 diabetes and significant cardiovascular disease risk, with metformin relegated to a second-line role.

Other cardiologists endorsed a more collaborative approach to prescribing empagliflozin and liraglutide.

Mitchel L. Zoler/Frontline Medical News

Mitchel L. Zoler/Frontline Medical News

Impact of heart failure in EMPA-REG

Roughly 10% of the 7,020 patients enrolled in EMPA-REG had heart failure at the time they entered the trial. During a median follow-up of just over 3 years, the incidence of new-onset heart failure – tallied as either a new heart failure hospitalization or a clinical episode deemed to be heart failure by an investigator – occurred in 4.6% of patients on empagliflozin and in 6.5% of patients in the placebo arm, a 1.9-percentage-point difference and a 30% relative risk reduction linked with empagliflozin use, Dr. Fitchett reported.

The main EMPA-REG outcome was a composite of cardiovascular death, nonfatal MI, and nonfatal stroke. This positive outcome in favor of empagliflozin treatment was primarily driven by a difference in the rate of cardiovascular death. In the new analysis, the relative reduction in cardiovascular deaths with empagliflozin compared with placebo was 29% among patients with prevalent heart failure at baseline, 35% among those who had an incident heart failure hospitalization during follow-up, 27% among patients with an incident heart failure episode diagnosed by an investigator during follow-up, 33% among the combined group of trial patients with any form of heart failure at trial entry or during the trial (those with prevalent heart failure at baseline plus those with an incident event), and 37% among the large number of patients in the trial who remained free from any indication of heart failure during follow-up.

In short, treatment with empagliflozin “reduced cardiovascular mortality by the same relative amount” regardless of whether patients did or did not have heart failure during the trial,” Dr. Fitchett concluded.

Additional secondary analyses from EMPA-REG reported at the ESC congress in August also documented that the benefit from empagliflozin treatment was roughly the same regardless of the age of patients enrolled in the trial and regardless of patients’ blood level of LDL cholesterol at entry into the study. These findings provide “confidence in the consistency of the effect” by empagliflozin, Dr. Fitchett said.

The endocrinologists’ view

“Most cardiologists are not thoroughly familiar with the full palette of medications for hyperglycemia. Selection of medication should not be made solely on the basis of results from a cardiovascular outcomes trial,” said Helena W. Rodbard, MD, a clinical endocrinologist in Rockville, Md.

[email protected]

On Twitter @mitchelzoler

The antidiabetic drugs that have recently shown efficacy for reducing cardiovascular-disease events in patients with type 2 diabetes have prompted some cardiologists to start acting a bit more like diabetologists.

The dramatic reduction in cardiovascular death and heart failure hospitalization seen during treatment with empagliflozin (Jardiance) in the EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial, for example, has prompted some cardiologists in the year since the first EMPA-REG report to become active prescribers of the drug to their patients who have type 2 diabetes and cardiovascular disease. The same evidence has driven other cardiologists who may not feel fully comfortable prescribing an antidiabetic drug on their own to enter into active partnerships with endocrinologists to work as a team to put diabetes patients with cardiovascular disease on empagliflozin.

Mitchel L. Zoler/Frontline Medical News

In Dr. Fitchett’s practice, “if a patient with type 2 diabetes has an endocrinologist, then I will send a letter to that physician saying I think the patient should be on one of these drugs,” empagliflozin or liraglutide, he said. “If the patient is being treated by a primary care physician, then I will prescribe empagliflozin myself because most primary care physicians are not willing to prescribe it. I think more and more cardiologists are doing this. The great thing about empagliflozin and liraglutide is that they do not cause hypoglycemia and the adverse effect profiles are relatively good. As long as drug cost is not an issue, then as cardiologists we need to adjust glycemia control with cardiovascular benefit as we did years ago with statin treatment,” explained Dr. Fitchett, a cardiologist at St. Michael’s Hospital in Toronto and a senior collaborator and coauthor on the EMPA-REG study.

When results from the 4S [Scandinavian Simvastatin Survival Study] came out in 1994, proving that long-term statin treatment was both safe and increased survival in patients with coronary heart disease, “cardiologists took over lipid management from endocrinologists,” he recalled. “We now have a safe and simple treatment for glucose lowering that also cuts cardiovascular disease events, so cardiologists have to also be involved, at least to some extent. Their degree of involvement depends on their practice and who provides a patient’s primary diabetes care,” he said.

Cardiologists vary on empagliflozin

Other cardiologists are mixed in their take on personally prescribing antidiabetic drugs to high-risk patients with type 2 diabetes. Greg C. Fonarow, MD, has also aggressively taken to empagliflozin over the past year, especially for his patients with heart failure or at high risk for developing heart failure. The EMPA-REG results showed that empagliflozin’s potent impact on reducing cardiovascular death in patients linked closely with a reduction in heart failure hospitalizations. In his recent experience, endocrinologists as well as other physicians who care for patients with type 2 diabetes “are often reluctant to make any changes [in a patient’s hypoglycemic regimen], and in general they have not gravitated toward the treatments that have been shown to improve cardiovascular outcomes and instead focus solely on a patient’s hemoglobin A_1c,” Dr. Fonarow said in an interview at the recent annual meeting of the Heart Failure Society of America.

Mitchel L. Zoler/Frontline Medical News

He said he prescribes empagliflozin to patients with type 2 diabetes if they are hospitalized for heart failure or as outpatients, and he targets it to patients diagnosed with heart failure – including heart failure with preserved ejection fraction – as well as to patients with other forms of cardiovascular disease, closely following the EMPA-REG enrollment criteria. It’s too early in the experience with empagliflozin to use it preferentially in diabetes patients without cardiovascular disease or patients who in any other way fall outside the enrollment criteria for EMPA-REG, he said.

“I am happy to consult with their endocrinologist, or I tell patients to discuss this treatment with their endocrinologist. If the endocrinologist prescribes empagliflozin, great; if not, I feel an obligation to provide the best care I can to my patients. This is not a hard medication to use. The safety profile is good. Treatment with empagliflozin obviously has renal-function considerations, but that’s true for many drugs. The biggest challenge is what is covered by the patient’s insurance. We often need preauthorization.

“So far I have seen excellent responses in patients for both metabolic control and clinical responses in patients with heart failure. Their symptoms seem to improve,” said Dr. Fonarow, professor of medicine and co-chief of cardiology at the University of Southern California , Los Angeles.

While Dr. Fonarow cautioned that he also would not start empagliflozin in a patient with a HbA_1c below 7%, he would seriously consider swapping out a patient’s drug for empagliflozin if it were a sulfonylurea or a dipeptidyl peptidase-4 inhibitor. He stopped short of suggesting a substitution of empagliflozin for metformin. In Dr. Fonarow’s opinion, the evidence for empagliflozin is also “more robust” than it has been for liraglutide or semaglutide. With what’s now known about the clinical impact of these drugs, he foresees a time when a combination between a SGLT-2 inhibitor, with its effect on heart failure, and a GLP-1 analogue, with its effect on atherosclerotic disease, may seem an ideal initial drug pairing for patients with type 2 diabetes and significant cardiovascular disease risk, with metformin relegated to a second-line role.

Other cardiologists endorsed a more collaborative approach to prescribing empagliflozin and liraglutide.

Mitchel L. Zoler/Frontline Medical News

Mitchel L. Zoler/Frontline Medical News

Impact of heart failure in EMPA-REG

Roughly 10% of the 7,020 patients enrolled in EMPA-REG had heart failure at the time they entered the trial. During a median follow-up of just over 3 years, the incidence of new-onset heart failure – tallied as either a new heart failure hospitalization or a clinical episode deemed to be heart failure by an investigator – occurred in 4.6% of patients on empagliflozin and in 6.5% of patients in the placebo arm, a 1.9-percentage-point difference and a 30% relative risk reduction linked with empagliflozin use, Dr. Fitchett reported.

The main EMPA-REG outcome was a composite of cardiovascular death, nonfatal MI, and nonfatal stroke. This positive outcome in favor of empagliflozin treatment was primarily driven by a difference in the rate of cardiovascular death. In the new analysis, the relative reduction in cardiovascular deaths with empagliflozin compared with placebo was 29% among patients with prevalent heart failure at baseline, 35% among those who had an incident heart failure hospitalization during follow-up, 27% among patients with an incident heart failure episode diagnosed by an investigator during follow-up, 33% among the combined group of trial patients with any form of heart failure at trial entry or during the trial (those with prevalent heart failure at baseline plus those with an incident event), and 37% among the large number of patients in the trial who remained free from any indication of heart failure during follow-up.

In short, treatment with empagliflozin “reduced cardiovascular mortality by the same relative amount” regardless of whether patients did or did not have heart failure during the trial,” Dr. Fitchett concluded.

Additional secondary analyses from EMPA-REG reported at the ESC congress in August also documented that the benefit from empagliflozin treatment was roughly the same regardless of the age of patients enrolled in the trial and regardless of patients’ blood level of LDL cholesterol at entry into the study. These findings provide “confidence in the consistency of the effect” by empagliflozin, Dr. Fitchett said.

The endocrinologists’ view

“Most cardiologists are not thoroughly familiar with the full palette of medications for hyperglycemia. Selection of medication should not be made solely on the basis of results from a cardiovascular outcomes trial,” said Helena W. Rodbard, MD, a clinical endocrinologist in Rockville, Md.

[email protected]

On Twitter @mitchelzoler

The antidiabetic drugs that have recently shown efficacy for reducing cardiovascular-disease events in patients with type 2 diabetes have prompted some cardiologists to start acting a bit more like diabetologists.

The dramatic reduction in cardiovascular death and heart failure hospitalization seen during treatment with empagliflozin (Jardiance) in the EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial, for example, has prompted some cardiologists in the year since the first EMPA-REG report to become active prescribers of the drug to their patients who have type 2 diabetes and cardiovascular disease. The same evidence has driven other cardiologists who may not feel fully comfortable prescribing an antidiabetic drug on their own to enter into active partnerships with endocrinologists to work as a team to put diabetes patients with cardiovascular disease on empagliflozin.

Mitchel L. Zoler/Frontline Medical News

In Dr. Fitchett’s practice, “if a patient with type 2 diabetes has an endocrinologist, then I will send a letter to that physician saying I think the patient should be on one of these drugs,” empagliflozin or liraglutide, he said. “If the patient is being treated by a primary care physician, then I will prescribe empagliflozin myself because most primary care physicians are not willing to prescribe it. I think more and more cardiologists are doing this. The great thing about empagliflozin and liraglutide is that they do not cause hypoglycemia and the adverse effect profiles are relatively good. As long as drug cost is not an issue, then as cardiologists we need to adjust glycemia control with cardiovascular benefit as we did years ago with statin treatment,” explained Dr. Fitchett, a cardiologist at St. Michael’s Hospital in Toronto and a senior collaborator and coauthor on the EMPA-REG study.

When results from the 4S [Scandinavian Simvastatin Survival Study] came out in 1994, proving that long-term statin treatment was both safe and increased survival in patients with coronary heart disease, “cardiologists took over lipid management from endocrinologists,” he recalled. “We now have a safe and simple treatment for glucose lowering that also cuts cardiovascular disease events, so cardiologists have to also be involved, at least to some extent. Their degree of involvement depends on their practice and who provides a patient’s primary diabetes care,” he said.

Cardiologists vary on empagliflozin

Other cardiologists are mixed in their take on personally prescribing antidiabetic drugs to high-risk patients with type 2 diabetes. Greg C. Fonarow, MD, has also aggressively taken to empagliflozin over the past year, especially for his patients with heart failure or at high risk for developing heart failure. The EMPA-REG results showed that empagliflozin’s potent impact on reducing cardiovascular death in patients linked closely with a reduction in heart failure hospitalizations. In his recent experience, endocrinologists as well as other physicians who care for patients with type 2 diabetes “are often reluctant to make any changes [in a patient’s hypoglycemic regimen], and in general they have not gravitated toward the treatments that have been shown to improve cardiovascular outcomes and instead focus solely on a patient’s hemoglobin A_1c,” Dr. Fonarow said in an interview at the recent annual meeting of the Heart Failure Society of America.

Mitchel L. Zoler/Frontline Medical News

He said he prescribes empagliflozin to patients with type 2 diabetes if they are hospitalized for heart failure or as outpatients, and he targets it to patients diagnosed with heart failure – including heart failure with preserved ejection fraction – as well as to patients with other forms of cardiovascular disease, closely following the EMPA-REG enrollment criteria. It’s too early in the experience with empagliflozin to use it preferentially in diabetes patients without cardiovascular disease or patients who in any other way fall outside the enrollment criteria for EMPA-REG, he said.

“I am happy to consult with their endocrinologist, or I tell patients to discuss this treatment with their endocrinologist. If the endocrinologist prescribes empagliflozin, great; if not, I feel an obligation to provide the best care I can to my patients. This is not a hard medication to use. The safety profile is good. Treatment with empagliflozin obviously has renal-function considerations, but that’s true for many drugs. The biggest challenge is what is covered by the patient’s insurance. We often need preauthorization.

“So far I have seen excellent responses in patients for both metabolic control and clinical responses in patients with heart failure. Their symptoms seem to improve,” said Dr. Fonarow, professor of medicine and co-chief of cardiology at the University of Southern California , Los Angeles.

While Dr. Fonarow cautioned that he also would not start empagliflozin in a patient with a HbA_1c below 7%, he would seriously consider swapping out a patient’s drug for empagliflozin if it were a sulfonylurea or a dipeptidyl peptidase-4 inhibitor. He stopped short of suggesting a substitution of empagliflozin for metformin. In Dr. Fonarow’s opinion, the evidence for empagliflozin is also “more robust” than it has been for liraglutide or semaglutide. With what’s now known about the clinical impact of these drugs, he foresees a time when a combination between a SGLT-2 inhibitor, with its effect on heart failure, and a GLP-1 analogue, with its effect on atherosclerotic disease, may seem an ideal initial drug pairing for patients with type 2 diabetes and significant cardiovascular disease risk, with metformin relegated to a second-line role.

Other cardiologists endorsed a more collaborative approach to prescribing empagliflozin and liraglutide.

Mitchel L. Zoler/Frontline Medical News

Mitchel L. Zoler/Frontline Medical News

Impact of heart failure in EMPA-REG

Roughly 10% of the 7,020 patients enrolled in EMPA-REG had heart failure at the time they entered the trial. During a median follow-up of just over 3 years, the incidence of new-onset heart failure – tallied as either a new heart failure hospitalization or a clinical episode deemed to be heart failure by an investigator – occurred in 4.6% of patients on empagliflozin and in 6.5% of patients in the placebo arm, a 1.9-percentage-point difference and a 30% relative risk reduction linked with empagliflozin use, Dr. Fitchett reported.

The main EMPA-REG outcome was a composite of cardiovascular death, nonfatal MI, and nonfatal stroke. This positive outcome in favor of empagliflozin treatment was primarily driven by a difference in the rate of cardiovascular death. In the new analysis, the relative reduction in cardiovascular deaths with empagliflozin compared with placebo was 29% among patients with prevalent heart failure at baseline, 35% among those who had an incident heart failure hospitalization during follow-up, 27% among patients with an incident heart failure episode diagnosed by an investigator during follow-up, 33% among the combined group of trial patients with any form of heart failure at trial entry or during the trial (those with prevalent heart failure at baseline plus those with an incident event), and 37% among the large number of patients in the trial who remained free from any indication of heart failure during follow-up.

In short, treatment with empagliflozin “reduced cardiovascular mortality by the same relative amount” regardless of whether patients did or did not have heart failure during the trial,” Dr. Fitchett concluded.

Additional secondary analyses from EMPA-REG reported at the ESC congress in August also documented that the benefit from empagliflozin treatment was roughly the same regardless of the age of patients enrolled in the trial and regardless of patients’ blood level of LDL cholesterol at entry into the study. These findings provide “confidence in the consistency of the effect” by empagliflozin, Dr. Fitchett said.

The endocrinologists’ view

“Most cardiologists are not thoroughly familiar with the full palette of medications for hyperglycemia. Selection of medication should not be made solely on the basis of results from a cardiovascular outcomes trial,” said Helena W. Rodbard, MD, a clinical endocrinologist in Rockville, Md.

[email protected]

On Twitter @mitchelzoler

SAN FRANCISCO – The pornography industry has taken over children’s sense of self and sexuality and warped their concept of what sex and a sexual identity is, said Gail Dines, PhD.

She challenged pediatricians to shape policy and help parents in wrangling back that control in a presentation at the annual meeting of the American Academy of Pediatrics.

Ulianna/Thinkstock

SAN FRANCISCO – The pornography industry has taken over children’s sense of self and sexuality and warped their concept of what sex and a sexual identity is, said Gail Dines, PhD.

She challenged pediatricians to shape policy and help parents in wrangling back that control in a presentation at the annual meeting of the American Academy of Pediatrics.

Ulianna/Thinkstock

SAN FRANCISCO – The pornography industry has taken over children’s sense of self and sexuality and warped their concept of what sex and a sexual identity is, said Gail Dines, PhD.

She challenged pediatricians to shape policy and help parents in wrangling back that control in a presentation at the annual meeting of the American Academy of Pediatrics.

Ulianna/Thinkstock

The use of outdated criteria for the identification of systemic sclerosis in primary biliary cholangitis likely led to an underestimation of the comorbidity’s prevalence.

Furthermore, more recent criteria estimate the prevalence of systemic sclerosis in primary biliary cholangitis to be around 23%.

[[{"fid":"172520","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Clinical appearance of acrosclerotic piece-meal necrosis of the first digit in a patient with systemic sclerosis.","field_file_image_credit[und][0][value]":"BMC Dermatology 2004, 4:11. doi:10.1186/1471-5945-4-11 ","field_file_image_caption[und][0][value]":""},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]In 1980, the American College of Rheumatology defined “highly specific but not sensitive” criteria for the identification of primary biliary cholangitis patients who also had systemic sclerosis, reported the study’s lead investigator Dr. Boyang Zheng of the University of Montreal Hospital Center and associates (J Rheumatol. 2016 Oct 28. doi: 10.3899/jrheum.160243).

In 2001, LeRoy and Medsger proposed and validated a new set of criteria that centrally required the observation of Raynaud phenomenon and “allowed for greater sensitivity and diagnosis of earlier disease by incorporating advances in nailfold capillary microscopy and [systemic sclerosis]–specific antibodies,” the investigators wrote.

Most recently, the ACR and the European League Against Rheumatism jointly developed new “weighted-point criteria endorsed for use in systemic sclerosis inclusion studies.” These new criteria, which were published in 2013, “the addition of at least a clinical or radiological feature to be positive.”

The purpose of this study, the first of its kind, according to investigators, was to compare the prevalence estimates of systemic sclerosis in primary biliary cholangitis patients as predicted by each of the three criteria sets.

A total of 100 patients who had previously been diagnosed with primary biliary cholangitis but not systemic sclerosis were recruited into the study. The majority of the patients were female (91%), the mean age at first visit was 57 years, and the mean primary biliary cholangitis Mayo score of disease severity and survival was 4.14.

At time of study enrollment, medical histories were obtained. All patients also underwent nailfold capillary microscopy, and serum samples were collected and analyzed for the presence of primary biliary cholangitis antibodies and the following systemic sclerosis–specific antibodies: anti–CENP-B, anti–topo I, anti–RNAP III, anti-Th/To.

Clinical data, presence of antibodies, and capillarascopic patterns were analyzed, and patients were retroactively evaluated for the fulfillment of each of the three systemic sclerosis criteria sets.

“A total of 23 patients satisfied at least one set of criteria, with 22 being positive for LeRoy and Medsger criteria, 17 for ACR/EULAR criteria, and only 1 for the ACR 1980 criteria,” Dr. Zheng and his associates reported.

The most frequent systemic sclerosis–associated features in the study population were Raynaud phenomenon (39%), systemic sclerosis antibodies (26%), abnormal nailfold capillary microscopy (20%), and capillary telangiectases (17%), while clinically evident skin changes were the most rare, investigators explained.

The 1980 ACR criteria likely led to an underestimation of systemic sclerosis in primary biliary cirrhosis, and given the benefit of early diagnosis and treatment of systemic sclerosis, patients with primary biliary cholangitis should be screened for Raynaud phenomenon and systemic sclerosis antibodies and undergo nailfold capillaroscopic microscopy, the investigators recommended.

“Clinicians need to remain alert for this sometimes insidious comorbidity,” the researchers added.

Dr. Zheng had no relevant financial disclosures.

[email protected]

On Twitter @jessnicolecraig

The use of outdated criteria for the identification of systemic sclerosis in primary biliary cholangitis likely led to an underestimation of the comorbidity’s prevalence.

Furthermore, more recent criteria estimate the prevalence of systemic sclerosis in primary biliary cholangitis to be around 23%.

[[{"fid":"172520","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Clinical appearance of acrosclerotic piece-meal necrosis of the first digit in a patient with systemic sclerosis.","field_file_image_credit[und][0][value]":"BMC Dermatology 2004, 4:11. doi:10.1186/1471-5945-4-11 ","field_file_image_caption[und][0][value]":""},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]In 1980, the American College of Rheumatology defined “highly specific but not sensitive” criteria for the identification of primary biliary cholangitis patients who also had systemic sclerosis, reported the study’s lead investigator Dr. Boyang Zheng of the University of Montreal Hospital Center and associates (J Rheumatol. 2016 Oct 28. doi: 10.3899/jrheum.160243).

In 2001, LeRoy and Medsger proposed and validated a new set of criteria that centrally required the observation of Raynaud phenomenon and “allowed for greater sensitivity and diagnosis of earlier disease by incorporating advances in nailfold capillary microscopy and [systemic sclerosis]–specific antibodies,” the investigators wrote.

Most recently, the ACR and the European League Against Rheumatism jointly developed new “weighted-point criteria endorsed for use in systemic sclerosis inclusion studies.” These new criteria, which were published in 2013, “the addition of at least a clinical or radiological feature to be positive.”

The purpose of this study, the first of its kind, according to investigators, was to compare the prevalence estimates of systemic sclerosis in primary biliary cholangitis patients as predicted by each of the three criteria sets.

A total of 100 patients who had previously been diagnosed with primary biliary cholangitis but not systemic sclerosis were recruited into the study. The majority of the patients were female (91%), the mean age at first visit was 57 years, and the mean primary biliary cholangitis Mayo score of disease severity and survival was 4.14.

At time of study enrollment, medical histories were obtained. All patients also underwent nailfold capillary microscopy, and serum samples were collected and analyzed for the presence of primary biliary cholangitis antibodies and the following systemic sclerosis–specific antibodies: anti–CENP-B, anti–topo I, anti–RNAP III, anti-Th/To.

Clinical data, presence of antibodies, and capillarascopic patterns were analyzed, and patients were retroactively evaluated for the fulfillment of each of the three systemic sclerosis criteria sets.

“A total of 23 patients satisfied at least one set of criteria, with 22 being positive for LeRoy and Medsger criteria, 17 for ACR/EULAR criteria, and only 1 for the ACR 1980 criteria,” Dr. Zheng and his associates reported.

The most frequent systemic sclerosis–associated features in the study population were Raynaud phenomenon (39%), systemic sclerosis antibodies (26%), abnormal nailfold capillary microscopy (20%), and capillary telangiectases (17%), while clinically evident skin changes were the most rare, investigators explained.

The 1980 ACR criteria likely led to an underestimation of systemic sclerosis in primary biliary cirrhosis, and given the benefit of early diagnosis and treatment of systemic sclerosis, patients with primary biliary cholangitis should be screened for Raynaud phenomenon and systemic sclerosis antibodies and undergo nailfold capillaroscopic microscopy, the investigators recommended.

“Clinicians need to remain alert for this sometimes insidious comorbidity,” the researchers added.

Dr. Zheng had no relevant financial disclosures.

[email protected]

On Twitter @jessnicolecraig

The use of outdated criteria for the identification of systemic sclerosis in primary biliary cholangitis likely led to an underestimation of the comorbidity’s prevalence.

Furthermore, more recent criteria estimate the prevalence of systemic sclerosis in primary biliary cholangitis to be around 23%.

[[{"fid":"172520","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Clinical appearance of acrosclerotic piece-meal necrosis of the first digit in a patient with systemic sclerosis.","field_file_image_credit[und][0][value]":"BMC Dermatology 2004, 4:11. doi:10.1186/1471-5945-4-11 ","field_file_image_caption[und][0][value]":""},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]In 1980, the American College of Rheumatology defined “highly specific but not sensitive” criteria for the identification of primary biliary cholangitis patients who also had systemic sclerosis, reported the study’s lead investigator Dr. Boyang Zheng of the University of Montreal Hospital Center and associates (J Rheumatol. 2016 Oct 28. doi: 10.3899/jrheum.160243).

In 2001, LeRoy and Medsger proposed and validated a new set of criteria that centrally required the observation of Raynaud phenomenon and “allowed for greater sensitivity and diagnosis of earlier disease by incorporating advances in nailfold capillary microscopy and [systemic sclerosis]–specific antibodies,” the investigators wrote.

Most recently, the ACR and the European League Against Rheumatism jointly developed new “weighted-point criteria endorsed for use in systemic sclerosis inclusion studies.” These new criteria, which were published in 2013, “the addition of at least a clinical or radiological feature to be positive.”

The purpose of this study, the first of its kind, according to investigators, was to compare the prevalence estimates of systemic sclerosis in primary biliary cholangitis patients as predicted by each of the three criteria sets.

A total of 100 patients who had previously been diagnosed with primary biliary cholangitis but not systemic sclerosis were recruited into the study. The majority of the patients were female (91%), the mean age at first visit was 57 years, and the mean primary biliary cholangitis Mayo score of disease severity and survival was 4.14.

At time of study enrollment, medical histories were obtained. All patients also underwent nailfold capillary microscopy, and serum samples were collected and analyzed for the presence of primary biliary cholangitis antibodies and the following systemic sclerosis–specific antibodies: anti–CENP-B, anti–topo I, anti–RNAP III, anti-Th/To.

Clinical data, presence of antibodies, and capillarascopic patterns were analyzed, and patients were retroactively evaluated for the fulfillment of each of the three systemic sclerosis criteria sets.

“A total of 23 patients satisfied at least one set of criteria, with 22 being positive for LeRoy and Medsger criteria, 17 for ACR/EULAR criteria, and only 1 for the ACR 1980 criteria,” Dr. Zheng and his associates reported.

The most frequent systemic sclerosis–associated features in the study population were Raynaud phenomenon (39%), systemic sclerosis antibodies (26%), abnormal nailfold capillary microscopy (20%), and capillary telangiectases (17%), while clinically evident skin changes were the most rare, investigators explained.

The 1980 ACR criteria likely led to an underestimation of systemic sclerosis in primary biliary cirrhosis, and given the benefit of early diagnosis and treatment of systemic sclerosis, patients with primary biliary cholangitis should be screened for Raynaud phenomenon and systemic sclerosis antibodies and undergo nailfold capillaroscopic microscopy, the investigators recommended.

“Clinicians need to remain alert for this sometimes insidious comorbidity,” the researchers added.

Dr. Zheng had no relevant financial disclosures.

[email protected]

On Twitter @jessnicolecraig

WASHINGTON – The era of powerful biologics has led to unforeseen surgical outcomes in patients with ulcerative colitis.

Patients undergoing surgery for ulcerative colitis now are 38% more likely to die in the hospital than they were 15 years ago, before infliximab and other biologics were adopted as medical therapy for the disease. A database review covering 18 years found that other surgical outcomes are worse, too, Jonathan Abelson, MD, said at the annual clinical congress of the American College of Surgeons.

[email protected]

On Twitter @Alz_Gal

WASHINGTON – The era of powerful biologics has led to unforeseen surgical outcomes in patients with ulcerative colitis.

Patients undergoing surgery for ulcerative colitis now are 38% more likely to die in the hospital than they were 15 years ago, before infliximab and other biologics were adopted as medical therapy for the disease. A database review covering 18 years found that other surgical outcomes are worse, too, Jonathan Abelson, MD, said at the annual clinical congress of the American College of Surgeons.

[email protected]

On Twitter @Alz_Gal

WASHINGTON – The era of powerful biologics has led to unforeseen surgical outcomes in patients with ulcerative colitis.

Patients undergoing surgery for ulcerative colitis now are 38% more likely to die in the hospital than they were 15 years ago, before infliximab and other biologics were adopted as medical therapy for the disease. A database review covering 18 years found that other surgical outcomes are worse, too, Jonathan Abelson, MD, said at the annual clinical congress of the American College of Surgeons.

[email protected]

On Twitter @Alz_Gal

School-located influenza vaccination (SLIV) increased seasonal influenza vaccination rates countywide and in both suburban and urban settings, a study found.

“Schools have a stake in influenza vaccination because immunization of schoolchildren can reduce absenteeism throughout the community. Nevertheless, only 6% of childhood influenza vaccinations occur at school. SLIV poses logistical challenges: obtaining parental consent, ordering and administering vaccine, and billing,” said Peter G. Szilagyi, MD, of Mattel Children’s Hospital, Los Angeles, and his associates.

©itsmejust/Thinkstock

[email protected]

School-located influenza vaccination (SLIV) increased seasonal influenza vaccination rates countywide and in both suburban and urban settings, a study found.

“Schools have a stake in influenza vaccination because immunization of schoolchildren can reduce absenteeism throughout the community. Nevertheless, only 6% of childhood influenza vaccinations occur at school. SLIV poses logistical challenges: obtaining parental consent, ordering and administering vaccine, and billing,” said Peter G. Szilagyi, MD, of Mattel Children’s Hospital, Los Angeles, and his associates.

©itsmejust/Thinkstock

[email protected]

School-located influenza vaccination (SLIV) increased seasonal influenza vaccination rates countywide and in both suburban and urban settings, a study found.

“Schools have a stake in influenza vaccination because immunization of schoolchildren can reduce absenteeism throughout the community. Nevertheless, only 6% of childhood influenza vaccinations occur at school. SLIV poses logistical challenges: obtaining parental consent, ordering and administering vaccine, and billing,” said Peter G. Szilagyi, MD, of Mattel Children’s Hospital, Los Angeles, and his associates.

©itsmejust/Thinkstock

[email protected]

ROME – Cardiorespiratory fitness provided strong and graded protection against all-cause mortality and nonfatal MI in a study of more than 5,000 patients treated for depression, Amjad M. Ahmed, MD, reported at the annual congress of the European Society of Cardiology.

“These results highlight the importance of assessing fitness to identify risk as well as promoting an active lifestyle in patients with depression,” said Dr. Ahmed of Abdulaziz University for Health Sciences in Riyadh, Saudi Arabia.

Bruce Jancin/Frontline Medical News

[email protected]
 

ROME – Cardiorespiratory fitness provided strong and graded protection against all-cause mortality and nonfatal MI in a study of more than 5,000 patients treated for depression, Amjad M. Ahmed, MD, reported at the annual congress of the European Society of Cardiology.

“These results highlight the importance of assessing fitness to identify risk as well as promoting an active lifestyle in patients with depression,” said Dr. Ahmed of Abdulaziz University for Health Sciences in Riyadh, Saudi Arabia.

Bruce Jancin/Frontline Medical News

[email protected]
 

ROME – Cardiorespiratory fitness provided strong and graded protection against all-cause mortality and nonfatal MI in a study of more than 5,000 patients treated for depression, Amjad M. Ahmed, MD, reported at the annual congress of the European Society of Cardiology.

“These results highlight the importance of assessing fitness to identify risk as well as promoting an active lifestyle in patients with depression,” said Dr. Ahmed of Abdulaziz University for Health Sciences in Riyadh, Saudi Arabia.

Bruce Jancin/Frontline Medical News

[email protected]
 

Carcinoembryonic antigen (CEA) is often used as a marker for relapse in colorectal cancer. But in as many as 40% of recurrences, the serum CEA shows unmeasurable elevations. And some patients with resected colorectal cancer (CRC) have transient elevations of CEA levels; the false-positive rate during follow-up has been as high as 16%, say researchers from Kaohsiung Medical University, Taiwan. They propose “a more powerful tool”: a membrane array-based multigene biomarker assay, or biomarker chip, which detects circulating tumor cells in the peripheral blood.

Related: Colorectal Carcinoma and Emerging Targeted Therapies

The researchers conducted a study in 298 patients with CRC to test that alternative. The patients were enrolled after radical curative resection for primary CRC tumor; 82 were stage I, 102 were stage II, and 114 were stage III. Patients were followed for a median of 28.4 months, every 3 months for 3 years, then every 6 months. At each follow-up visit, laboratory studies included serum CEA levels. Elevated CEA levels were defined as 2 consecutive measurements of >5 ng/mL at a 3-month interval.

During the study period, 48 patients (16.1%) had postoperative relapse, and 26 (8.7%) died. Of all 298 patients, 62 (20.8%) had a total biomarker chip score higher than the cutoff value. Of the 48 who relapsed, 42 (87.5%) showed positive biochip results prior to relapse.

The positive biochip results were significantly associated with postoperative relapse. In fact, the biomarker chip was better for predicting relapse than were the postoperative serum CEA levels with higher sensitivity (87.5% vs 60.4%), specificity (92.0% vs 83.2%), positive predictive value (67.7% vs 40.8%), negative predictive value (97.5% vs 91.6%), and accuracy (91.3% vs 79.5%).

Moreover, the biochip predicted relapse “considerably earlier” than did CEA levels (10.7 vs 2.8 months). The researchers note that CRC-related deaths are largely attributable to clinical relapse. The sooner a relapse is diagnosed, the more amenable the tumor may be to resection, increasing the likelihood of long-term survival.

Related: Strollin’ the Colon: A Collaborated Effort to Provide Education and Screening Outreach for the Improvement of Awareness, Access, and Early Detection of Colorectal Cancer

In sum, the biomarker chip would be a more accurate tool for predicting relapse, the researchers say. They also suggest that, in clinical practice, combining the 2 tests could enhance confidence in the diagnosis.

Source:
Chang YT, Huang MY, Huang CW, et al. PLoS One. 2016;11(10):e0163264.
doi:  10.1371/journal.pone.0163264.

Carcinoembryonic antigen (CEA) is often used as a marker for relapse in colorectal cancer. But in as many as 40% of recurrences, the serum CEA shows unmeasurable elevations. And some patients with resected colorectal cancer (CRC) have transient elevations of CEA levels; the false-positive rate during follow-up has been as high as 16%, say researchers from Kaohsiung Medical University, Taiwan. They propose “a more powerful tool”: a membrane array-based multigene biomarker assay, or biomarker chip, which detects circulating tumor cells in the peripheral blood.

Related: Colorectal Carcinoma and Emerging Targeted Therapies

The researchers conducted a study in 298 patients with CRC to test that alternative. The patients were enrolled after radical curative resection for primary CRC tumor; 82 were stage I, 102 were stage II, and 114 were stage III. Patients were followed for a median of 28.4 months, every 3 months for 3 years, then every 6 months. At each follow-up visit, laboratory studies included serum CEA levels. Elevated CEA levels were defined as 2 consecutive measurements of >5 ng/mL at a 3-month interval.

During the study period, 48 patients (16.1%) had postoperative relapse, and 26 (8.7%) died. Of all 298 patients, 62 (20.8%) had a total biomarker chip score higher than the cutoff value. Of the 48 who relapsed, 42 (87.5%) showed positive biochip results prior to relapse.

The positive biochip results were significantly associated with postoperative relapse. In fact, the biomarker chip was better for predicting relapse than were the postoperative serum CEA levels with higher sensitivity (87.5% vs 60.4%), specificity (92.0% vs 83.2%), positive predictive value (67.7% vs 40.8%), negative predictive value (97.5% vs 91.6%), and accuracy (91.3% vs 79.5%).

Moreover, the biochip predicted relapse “considerably earlier” than did CEA levels (10.7 vs 2.8 months). The researchers note that CRC-related deaths are largely attributable to clinical relapse. The sooner a relapse is diagnosed, the more amenable the tumor may be to resection, increasing the likelihood of long-term survival.

Related: Strollin’ the Colon: A Collaborated Effort to Provide Education and Screening Outreach for the Improvement of Awareness, Access, and Early Detection of Colorectal Cancer

In sum, the biomarker chip would be a more accurate tool for predicting relapse, the researchers say. They also suggest that, in clinical practice, combining the 2 tests could enhance confidence in the diagnosis.

Source:
Chang YT, Huang MY, Huang CW, et al. PLoS One. 2016;11(10):e0163264.
doi:  10.1371/journal.pone.0163264.

Carcinoembryonic antigen (CEA) is often used as a marker for relapse in colorectal cancer. But in as many as 40% of recurrences, the serum CEA shows unmeasurable elevations. And some patients with resected colorectal cancer (CRC) have transient elevations of CEA levels; the false-positive rate during follow-up has been as high as 16%, say researchers from Kaohsiung Medical University, Taiwan. They propose “a more powerful tool”: a membrane array-based multigene biomarker assay, or biomarker chip, which detects circulating tumor cells in the peripheral blood.

Related: Colorectal Carcinoma and Emerging Targeted Therapies

The researchers conducted a study in 298 patients with CRC to test that alternative. The patients were enrolled after radical curative resection for primary CRC tumor; 82 were stage I, 102 were stage II, and 114 were stage III. Patients were followed for a median of 28.4 months, every 3 months for 3 years, then every 6 months. At each follow-up visit, laboratory studies included serum CEA levels. Elevated CEA levels were defined as 2 consecutive measurements of >5 ng/mL at a 3-month interval.

During the study period, 48 patients (16.1%) had postoperative relapse, and 26 (8.7%) died. Of all 298 patients, 62 (20.8%) had a total biomarker chip score higher than the cutoff value. Of the 48 who relapsed, 42 (87.5%) showed positive biochip results prior to relapse.

The positive biochip results were significantly associated with postoperative relapse. In fact, the biomarker chip was better for predicting relapse than were the postoperative serum CEA levels with higher sensitivity (87.5% vs 60.4%), specificity (92.0% vs 83.2%), positive predictive value (67.7% vs 40.8%), negative predictive value (97.5% vs 91.6%), and accuracy (91.3% vs 79.5%).

Moreover, the biochip predicted relapse “considerably earlier” than did CEA levels (10.7 vs 2.8 months). The researchers note that CRC-related deaths are largely attributable to clinical relapse. The sooner a relapse is diagnosed, the more amenable the tumor may be to resection, increasing the likelihood of long-term survival.

Related: Strollin’ the Colon: A Collaborated Effort to Provide Education and Screening Outreach for the Improvement of Awareness, Access, and Early Detection of Colorectal Cancer

In sum, the biomarker chip would be a more accurate tool for predicting relapse, the researchers say. They also suggest that, in clinical practice, combining the 2 tests could enhance confidence in the diagnosis.

Source:
Chang YT, Huang MY, Huang CW, et al. PLoS One. 2016;11(10):e0163264.
doi:  10.1371/journal.pone.0163264.