Melkersson-Rosenthal syndrome (MRS) is a rare condition comprised of unilateral peripheral facial nerve palsy, episodic or progressive facial edema, and lingua plicata (also known as fissured tongue). Melkersson-Rosenthal syndrome is a subtype of orofacial granulomatosis and often is mistaken for angioedema or pseudoangioedema due to the swelling of the lips and eyelids. We present a case of MRS that cleared in response to adalimumab therapy.

Case Report

A 69-year-old woman presented to our dermatology clinic with facial edema and a fissured tongue of 4 years’ duration. These symptoms had failed to improve with doxycycline, tacrolimus ointment 0.1%, and cortisone injections of the upper lip, as well as a balsam-free diet, fragrance-free skin products, and flavor-free toothpaste prescribed by multiple physicians over 4 years. Two weeks prior to the current presentation the patient developed left facial nerve palsy that was diagnosed by an outside physician as Bell palsy, and the patient completed a 7-day course of prednisone 1 day prior to presentation. The patient’s medical history was remarkable for type 2 diabetes mellitus controlled with metformin, hyperlipidemia controlled with ezetimibe-simvastatin, and psoriasis. She reported no family history of autoimmune or dermatologic disorders and denied any fever, unintentional weight loss, nausea, vomiting, or diarrhea.

On physical examination, the patient had considerable perioral edema and erythema without warmth or tenderness (Figure 1A). The tongue was fissured with notable scalloping at the lateral margins (Figure 1B). There were no aphthous ulcers or lymphadenopathy, and the remainder of the neurologic examination was normal. The patient had erythematous plaques with scaling on the bilateral elbows. Cardiopulmonary, musculoskeletal, and abdominal examinations were otherwise normal.

Laboratory data revealed an elevated white blood cell count of 17,500/µL (reference range, 4500–11,000/µL), an elevated absolute neutrophil count of 14,018/µL (reference range, 0–700/µL), and an absolute eosinophil count of 0/µL (reference range, 0–450/µL), with the rest of the complete blood cell count within reference range. A basic metabolic panel showed an elevated glucose level of 326 mg/dL (reference range, 70–110 mg/dL), consistent with diabetes and most likely exacerbated by the recent steroid course. A lipid panel was consistent with diagnosed hyperlipidemia (total cholesterol, 236 mg/dL [reference range, <200 mg/dL]; low-density lipoprotein, 134 mg/dL [reference range, 10–30 mg/dL]; triglycerides, 188 mg/dL [reference range, <160 mg/dL]). Hepatitis B and C tests were negative. A punch biopsy of the buccal and labial mucosa was taken, revealing a parakeratinized stratified squamous epithelium with an unusual pattern of surface keratinization with foci of intracellular and extracellular edema in the spinous layer. The underlying fibrous connective tissue was edematous with infiltrates of lymphocytes, mast cells, macrophages, and a few plasma cells. The pathology report listed the diagnosis as nonspecific “chronic mucositis,” with a list of differential diagnoses that included angioedema, hypersensitivity reaction, or other possible autoimmune disorders.

On consideration of these differential diagnoses, it was felt most likely to be MRS, which remains a primarily clinical diagnosis characterized by the triad of symptoms seen in this patient. Treatment of this condition emphasizes inflammation, and steroid therapy often is utilized, as it was in our patient. After the diagnosis of MRS was made, the patient received adalimumab 80 mg subcutaneously on day 1 and 40 mg on day 8 as a loading dose; she subsequently began a course of subcutaneous injections of adalimumab 40 mg once every other week for treatment of psoriasis with the goal of simultaneously treating the MRS. The symptoms did not completely resolve at this dose, so it was increased to 40 mg once weekly. The patient reported that the facial edema, lingua plicata, and facial nerve palsy resolved concomitantly over approximately 3 months with greater improvement at 5 months (Figure 2). The patient has had no relapses as of the last follow-up at 11 months.

Comment

Melkersson-Rosenthal syndrome usually presents sporadically, though there are reports of familial association,^1-3 and only 8% to 25% of patients worldwide present with the complete triad of symptoms.⁴ The pathogenesis of the syndrome is controversial. Granulomatous changes have been found in patients experiencing chronic edema. However, according to Zimmer et al⁵ in a study of 42 MRS patients, only 46% (19/42) had granulomatous changes; 36% (15/42) had nonspecific inflammation, 11% (5/42) had incidental findings, and 7% (3/42) showed no histopathologic abnormalities. Granulomatous cheilitis is a subtype of orofacial granulomatosis, an idiopathic process that causes swelling of the face and lips as well as intraoral swelling and ulceration. Orofacial granulomatosis is referred to as granulomatous cheilitis when the lip is involved. Melkersson-Rosenthal syndrome is another subtype of orofacial granulomatosis that includes facial palsy and fissured tongue.^6,7

In a clinical study of 7 patients with MRS, Liu and Yu¹ found 3 (42%) patients to have dysarthria, dysphagia, and tongue muscle atrophy; 1 patient to have migrainelike headaches; 1 patient to have decreased vision and an ocular movement disorder; 1 patient to have ipsilateral hearing loss; and 1 patient to lack any other symptoms. Halevy et al⁸ suggested a possible association of MRS with psoriasis. In their review of 12 patients, 1 (8%) had psoriatic arthritis, 2 (17%) had skin biopsy–proven psoriasis, and 3 (25%) had a family history of psoriasis.⁸ Because the disease is quite rare, it is difficult to determine other symptoms that may be associated with the disease.

Tumor necrosis factor α (TNF-α) is needed for granuloma formation, and TNF-α antagonists have been used to treat a number of granulomatous conditions including Crohn disease and sarcoidosis.^9-11 Two case reports indicate that infliximab, a mouse/human chimeric monoclonal antibody to TNF-α, has been used successfully to clear MRS.^12,13 One report cited the use of adalimumab for maintenance therapy of MRS,¹² and more recently, adalimumab has been reported for refractory MRS.¹⁴ However, there currently are no known reports regarding the efficacy of adalimumab as a first-line treatment of MRS.

Adalimumab is a fully human monoclonal antibody to TNF-α, which is administered via subcutaneous injections. Infliximab must be administered at an infusion center, making treatment logistically more difficult for patients, and can be associated with the development of infusion reactions, though the exact data on infusion reactions are difficult to estimate due to variations in reporting.^15,16

In 2014, Stein et al¹⁴ reported a case of refractory MRS in a 29-year-old man associated with acute attacks of hearing loss. The patient’s symptoms were controlled with high-dose prednisolone but were unable to be maintained on methotrexate or azathioprine as steroid-sparing agents. The patient was loaded with adalimumab 80 mg subcutaneously once on day 1 and was continued on 40 mg subcutaneously once every 3 weeks, gradually extending to once every 4 weeks when symptoms improved. The patient was slowly weaned off prednisolone 16 months after starting adalimumab. After 20 months, adalimumab therapy was discontinued and the patient remained recurrence free at 4 years’ follow-up.¹⁴ In another case, adalimumab was utilized as maintenance therapy after initial improvement with infliximab.¹² Kakimoto et al¹² reported a previously healthy 19-year-old woman with edema of the bilateral eyelids and upper lip. The authors determined the patient had MRS despite the lack of fissured tongue or facial nerve palsy and started infliximab. The condition resolved after the patient’s second infusion of infliximab and completely cleared after the third infusion; however, she had logistical difficulties reaching the infusion center and disliked the flulike response she experienced with the treatment. She was started on once weekly subcutaneous injections of adalimumab 40 mg and did not relapse.¹² Another patient with granulomatous cheilitis responded to adalimumab after corticosteroids, intralesional injections of triamcinolone, topical tacrolimus, roxithromycin, and clofazimine failed.¹⁷ The patient received adalimumab 80 mg for the first week and 40 mg for the second week and every 2 weeks thereafter. The patient began improving after the third dose and remained relapse free for at least 6 months of follow-up.¹⁷

Conclusion

We present a case of a 69-year-old woman who presented with facial nerve palsy, facial edema, and a fissured tongue, which is the classic triad of MRS, and all 3 symptoms improved with adalimumab.

Melkersson-Rosenthal syndrome (MRS) is a rare condition comprised of unilateral peripheral facial nerve palsy, episodic or progressive facial edema, and lingua plicata (also known as fissured tongue). Melkersson-Rosenthal syndrome is a subtype of orofacial granulomatosis and often is mistaken for angioedema or pseudoangioedema due to the swelling of the lips and eyelids. We present a case of MRS that cleared in response to adalimumab therapy.

Case Report

A 69-year-old woman presented to our dermatology clinic with facial edema and a fissured tongue of 4 years’ duration. These symptoms had failed to improve with doxycycline, tacrolimus ointment 0.1%, and cortisone injections of the upper lip, as well as a balsam-free diet, fragrance-free skin products, and flavor-free toothpaste prescribed by multiple physicians over 4 years. Two weeks prior to the current presentation the patient developed left facial nerve palsy that was diagnosed by an outside physician as Bell palsy, and the patient completed a 7-day course of prednisone 1 day prior to presentation. The patient’s medical history was remarkable for type 2 diabetes mellitus controlled with metformin, hyperlipidemia controlled with ezetimibe-simvastatin, and psoriasis. She reported no family history of autoimmune or dermatologic disorders and denied any fever, unintentional weight loss, nausea, vomiting, or diarrhea.

On physical examination, the patient had considerable perioral edema and erythema without warmth or tenderness (Figure 1A). The tongue was fissured with notable scalloping at the lateral margins (Figure 1B). There were no aphthous ulcers or lymphadenopathy, and the remainder of the neurologic examination was normal. The patient had erythematous plaques with scaling on the bilateral elbows. Cardiopulmonary, musculoskeletal, and abdominal examinations were otherwise normal.

Laboratory data revealed an elevated white blood cell count of 17,500/µL (reference range, 4500–11,000/µL), an elevated absolute neutrophil count of 14,018/µL (reference range, 0–700/µL), and an absolute eosinophil count of 0/µL (reference range, 0–450/µL), with the rest of the complete blood cell count within reference range. A basic metabolic panel showed an elevated glucose level of 326 mg/dL (reference range, 70–110 mg/dL), consistent with diabetes and most likely exacerbated by the recent steroid course. A lipid panel was consistent with diagnosed hyperlipidemia (total cholesterol, 236 mg/dL [reference range, <200 mg/dL]; low-density lipoprotein, 134 mg/dL [reference range, 10–30 mg/dL]; triglycerides, 188 mg/dL [reference range, <160 mg/dL]). Hepatitis B and C tests were negative. A punch biopsy of the buccal and labial mucosa was taken, revealing a parakeratinized stratified squamous epithelium with an unusual pattern of surface keratinization with foci of intracellular and extracellular edema in the spinous layer. The underlying fibrous connective tissue was edematous with infiltrates of lymphocytes, mast cells, macrophages, and a few plasma cells. The pathology report listed the diagnosis as nonspecific “chronic mucositis,” with a list of differential diagnoses that included angioedema, hypersensitivity reaction, or other possible autoimmune disorders.

On consideration of these differential diagnoses, it was felt most likely to be MRS, which remains a primarily clinical diagnosis characterized by the triad of symptoms seen in this patient. Treatment of this condition emphasizes inflammation, and steroid therapy often is utilized, as it was in our patient. After the diagnosis of MRS was made, the patient received adalimumab 80 mg subcutaneously on day 1 and 40 mg on day 8 as a loading dose; she subsequently began a course of subcutaneous injections of adalimumab 40 mg once every other week for treatment of psoriasis with the goal of simultaneously treating the MRS. The symptoms did not completely resolve at this dose, so it was increased to 40 mg once weekly. The patient reported that the facial edema, lingua plicata, and facial nerve palsy resolved concomitantly over approximately 3 months with greater improvement at 5 months (Figure 2). The patient has had no relapses as of the last follow-up at 11 months.

Comment

Melkersson-Rosenthal syndrome usually presents sporadically, though there are reports of familial association,^1-3 and only 8% to 25% of patients worldwide present with the complete triad of symptoms.⁴ The pathogenesis of the syndrome is controversial. Granulomatous changes have been found in patients experiencing chronic edema. However, according to Zimmer et al⁵ in a study of 42 MRS patients, only 46% (19/42) had granulomatous changes; 36% (15/42) had nonspecific inflammation, 11% (5/42) had incidental findings, and 7% (3/42) showed no histopathologic abnormalities. Granulomatous cheilitis is a subtype of orofacial granulomatosis, an idiopathic process that causes swelling of the face and lips as well as intraoral swelling and ulceration. Orofacial granulomatosis is referred to as granulomatous cheilitis when the lip is involved. Melkersson-Rosenthal syndrome is another subtype of orofacial granulomatosis that includes facial palsy and fissured tongue.^6,7

In a clinical study of 7 patients with MRS, Liu and Yu¹ found 3 (42%) patients to have dysarthria, dysphagia, and tongue muscle atrophy; 1 patient to have migrainelike headaches; 1 patient to have decreased vision and an ocular movement disorder; 1 patient to have ipsilateral hearing loss; and 1 patient to lack any other symptoms. Halevy et al⁸ suggested a possible association of MRS with psoriasis. In their review of 12 patients, 1 (8%) had psoriatic arthritis, 2 (17%) had skin biopsy–proven psoriasis, and 3 (25%) had a family history of psoriasis.⁸ Because the disease is quite rare, it is difficult to determine other symptoms that may be associated with the disease.

Tumor necrosis factor α (TNF-α) is needed for granuloma formation, and TNF-α antagonists have been used to treat a number of granulomatous conditions including Crohn disease and sarcoidosis.^9-11 Two case reports indicate that infliximab, a mouse/human chimeric monoclonal antibody to TNF-α, has been used successfully to clear MRS.^12,13 One report cited the use of adalimumab for maintenance therapy of MRS,¹² and more recently, adalimumab has been reported for refractory MRS.¹⁴ However, there currently are no known reports regarding the efficacy of adalimumab as a first-line treatment of MRS.

Adalimumab is a fully human monoclonal antibody to TNF-α, which is administered via subcutaneous injections. Infliximab must be administered at an infusion center, making treatment logistically more difficult for patients, and can be associated with the development of infusion reactions, though the exact data on infusion reactions are difficult to estimate due to variations in reporting.^15,16

In 2014, Stein et al¹⁴ reported a case of refractory MRS in a 29-year-old man associated with acute attacks of hearing loss. The patient’s symptoms were controlled with high-dose prednisolone but were unable to be maintained on methotrexate or azathioprine as steroid-sparing agents. The patient was loaded with adalimumab 80 mg subcutaneously once on day 1 and was continued on 40 mg subcutaneously once every 3 weeks, gradually extending to once every 4 weeks when symptoms improved. The patient was slowly weaned off prednisolone 16 months after starting adalimumab. After 20 months, adalimumab therapy was discontinued and the patient remained recurrence free at 4 years’ follow-up.¹⁴ In another case, adalimumab was utilized as maintenance therapy after initial improvement with infliximab.¹² Kakimoto et al¹² reported a previously healthy 19-year-old woman with edema of the bilateral eyelids and upper lip. The authors determined the patient had MRS despite the lack of fissured tongue or facial nerve palsy and started infliximab. The condition resolved after the patient’s second infusion of infliximab and completely cleared after the third infusion; however, she had logistical difficulties reaching the infusion center and disliked the flulike response she experienced with the treatment. She was started on once weekly subcutaneous injections of adalimumab 40 mg and did not relapse.¹² Another patient with granulomatous cheilitis responded to adalimumab after corticosteroids, intralesional injections of triamcinolone, topical tacrolimus, roxithromycin, and clofazimine failed.¹⁷ The patient received adalimumab 80 mg for the first week and 40 mg for the second week and every 2 weeks thereafter. The patient began improving after the third dose and remained relapse free for at least 6 months of follow-up.¹⁷

Conclusion

We present a case of a 69-year-old woman who presented with facial nerve palsy, facial edema, and a fissured tongue, which is the classic triad of MRS, and all 3 symptoms improved with adalimumab.

Melkersson-Rosenthal syndrome (MRS) is a rare condition comprised of unilateral peripheral facial nerve palsy, episodic or progressive facial edema, and lingua plicata (also known as fissured tongue). Melkersson-Rosenthal syndrome is a subtype of orofacial granulomatosis and often is mistaken for angioedema or pseudoangioedema due to the swelling of the lips and eyelids. We present a case of MRS that cleared in response to adalimumab therapy.

Case Report

A 69-year-old woman presented to our dermatology clinic with facial edema and a fissured tongue of 4 years’ duration. These symptoms had failed to improve with doxycycline, tacrolimus ointment 0.1%, and cortisone injections of the upper lip, as well as a balsam-free diet, fragrance-free skin products, and flavor-free toothpaste prescribed by multiple physicians over 4 years. Two weeks prior to the current presentation the patient developed left facial nerve palsy that was diagnosed by an outside physician as Bell palsy, and the patient completed a 7-day course of prednisone 1 day prior to presentation. The patient’s medical history was remarkable for type 2 diabetes mellitus controlled with metformin, hyperlipidemia controlled with ezetimibe-simvastatin, and psoriasis. She reported no family history of autoimmune or dermatologic disorders and denied any fever, unintentional weight loss, nausea, vomiting, or diarrhea.

On physical examination, the patient had considerable perioral edema and erythema without warmth or tenderness (Figure 1A). The tongue was fissured with notable scalloping at the lateral margins (Figure 1B). There were no aphthous ulcers or lymphadenopathy, and the remainder of the neurologic examination was normal. The patient had erythematous plaques with scaling on the bilateral elbows. Cardiopulmonary, musculoskeletal, and abdominal examinations were otherwise normal.

Laboratory data revealed an elevated white blood cell count of 17,500/µL (reference range, 4500–11,000/µL), an elevated absolute neutrophil count of 14,018/µL (reference range, 0–700/µL), and an absolute eosinophil count of 0/µL (reference range, 0–450/µL), with the rest of the complete blood cell count within reference range. A basic metabolic panel showed an elevated glucose level of 326 mg/dL (reference range, 70–110 mg/dL), consistent with diabetes and most likely exacerbated by the recent steroid course. A lipid panel was consistent with diagnosed hyperlipidemia (total cholesterol, 236 mg/dL [reference range, <200 mg/dL]; low-density lipoprotein, 134 mg/dL [reference range, 10–30 mg/dL]; triglycerides, 188 mg/dL [reference range, <160 mg/dL]). Hepatitis B and C tests were negative. A punch biopsy of the buccal and labial mucosa was taken, revealing a parakeratinized stratified squamous epithelium with an unusual pattern of surface keratinization with foci of intracellular and extracellular edema in the spinous layer. The underlying fibrous connective tissue was edematous with infiltrates of lymphocytes, mast cells, macrophages, and a few plasma cells. The pathology report listed the diagnosis as nonspecific “chronic mucositis,” with a list of differential diagnoses that included angioedema, hypersensitivity reaction, or other possible autoimmune disorders.

On consideration of these differential diagnoses, it was felt most likely to be MRS, which remains a primarily clinical diagnosis characterized by the triad of symptoms seen in this patient. Treatment of this condition emphasizes inflammation, and steroid therapy often is utilized, as it was in our patient. After the diagnosis of MRS was made, the patient received adalimumab 80 mg subcutaneously on day 1 and 40 mg on day 8 as a loading dose; she subsequently began a course of subcutaneous injections of adalimumab 40 mg once every other week for treatment of psoriasis with the goal of simultaneously treating the MRS. The symptoms did not completely resolve at this dose, so it was increased to 40 mg once weekly. The patient reported that the facial edema, lingua plicata, and facial nerve palsy resolved concomitantly over approximately 3 months with greater improvement at 5 months (Figure 2). The patient has had no relapses as of the last follow-up at 11 months.

Comment

Melkersson-Rosenthal syndrome usually presents sporadically, though there are reports of familial association,^1-3 and only 8% to 25% of patients worldwide present with the complete triad of symptoms.⁴ The pathogenesis of the syndrome is controversial. Granulomatous changes have been found in patients experiencing chronic edema. However, according to Zimmer et al⁵ in a study of 42 MRS patients, only 46% (19/42) had granulomatous changes; 36% (15/42) had nonspecific inflammation, 11% (5/42) had incidental findings, and 7% (3/42) showed no histopathologic abnormalities. Granulomatous cheilitis is a subtype of orofacial granulomatosis, an idiopathic process that causes swelling of the face and lips as well as intraoral swelling and ulceration. Orofacial granulomatosis is referred to as granulomatous cheilitis when the lip is involved. Melkersson-Rosenthal syndrome is another subtype of orofacial granulomatosis that includes facial palsy and fissured tongue.^6,7

In a clinical study of 7 patients with MRS, Liu and Yu¹ found 3 (42%) patients to have dysarthria, dysphagia, and tongue muscle atrophy; 1 patient to have migrainelike headaches; 1 patient to have decreased vision and an ocular movement disorder; 1 patient to have ipsilateral hearing loss; and 1 patient to lack any other symptoms. Halevy et al⁸ suggested a possible association of MRS with psoriasis. In their review of 12 patients, 1 (8%) had psoriatic arthritis, 2 (17%) had skin biopsy–proven psoriasis, and 3 (25%) had a family history of psoriasis.⁸ Because the disease is quite rare, it is difficult to determine other symptoms that may be associated with the disease.

Tumor necrosis factor α (TNF-α) is needed for granuloma formation, and TNF-α antagonists have been used to treat a number of granulomatous conditions including Crohn disease and sarcoidosis.^9-11 Two case reports indicate that infliximab, a mouse/human chimeric monoclonal antibody to TNF-α, has been used successfully to clear MRS.^12,13 One report cited the use of adalimumab for maintenance therapy of MRS,¹² and more recently, adalimumab has been reported for refractory MRS.¹⁴ However, there currently are no known reports regarding the efficacy of adalimumab as a first-line treatment of MRS.

Adalimumab is a fully human monoclonal antibody to TNF-α, which is administered via subcutaneous injections. Infliximab must be administered at an infusion center, making treatment logistically more difficult for patients, and can be associated with the development of infusion reactions, though the exact data on infusion reactions are difficult to estimate due to variations in reporting.^15,16

In 2014, Stein et al¹⁴ reported a case of refractory MRS in a 29-year-old man associated with acute attacks of hearing loss. The patient’s symptoms were controlled with high-dose prednisolone but were unable to be maintained on methotrexate or azathioprine as steroid-sparing agents. The patient was loaded with adalimumab 80 mg subcutaneously once on day 1 and was continued on 40 mg subcutaneously once every 3 weeks, gradually extending to once every 4 weeks when symptoms improved. The patient was slowly weaned off prednisolone 16 months after starting adalimumab. After 20 months, adalimumab therapy was discontinued and the patient remained recurrence free at 4 years’ follow-up.¹⁴ In another case, adalimumab was utilized as maintenance therapy after initial improvement with infliximab.¹² Kakimoto et al¹² reported a previously healthy 19-year-old woman with edema of the bilateral eyelids and upper lip. The authors determined the patient had MRS despite the lack of fissured tongue or facial nerve palsy and started infliximab. The condition resolved after the patient’s second infusion of infliximab and completely cleared after the third infusion; however, she had logistical difficulties reaching the infusion center and disliked the flulike response she experienced with the treatment. She was started on once weekly subcutaneous injections of adalimumab 40 mg and did not relapse.¹² Another patient with granulomatous cheilitis responded to adalimumab after corticosteroids, intralesional injections of triamcinolone, topical tacrolimus, roxithromycin, and clofazimine failed.¹⁷ The patient received adalimumab 80 mg for the first week and 40 mg for the second week and every 2 weeks thereafter. The patient began improving after the third dose and remained relapse free for at least 6 months of follow-up.¹⁷

Conclusion

We present a case of a 69-year-old woman who presented with facial nerve palsy, facial edema, and a fissured tongue, which is the classic triad of MRS, and all 3 symptoms improved with adalimumab.

Myth: Biologics Work Slowly

Biologics have demonstrated efficacy in psoriasis and often are used in psoriasis patients who have not achieved desired results with other treatments, patients who have had intolerable side effects from other treatments, and patients with concurrent diseases that preclude the use of systemic therapies. Because of the quality-of-life impact of psoriasis, patients look for quick clearance of their symptoms, but can biologics deliver fast results or do they work slowly?

Biologics such as etanercept and adalimumab block tumor necrosis factor α signaling, while ustekinumab targets IL-12 and IL-23 and others target IL-17. Some patients may begin to see improvement in skin lesions within 1 month of initiating biologic therapies because they target specific proinflammatory pathways that are critical to the pathogenesis of psoriasis, but response time varies among patients and specific therapy used.

The psoriasis area and severity index (PASI) measures psoriasis treatment success. Based on the American Academy of Dermatology’s guidelines of care for the management of psoriasis and psoriatic arthritis published in 2008, short-term response was achieved in 10 to 14 weeks for the following biologics:

• Adalimumab: 80% of patients achieved PASI 75 at week 12
• Etanercept: 49% of patients given 50 mg twice weekly achieved PASI 75 at 12 weeks; 34% of patients given 25 mg twice weekly achieved PASI 75 at 12 weeks
• Infliximab: 80% of patients achieved PASI 75 at week 10

Of the newer biologics, Premier Research recently noted that PASI 75 was achieved after 12 weeks with the following biologics:

• Brodalumab: 83% after 12 weeks
• Ixekizumab: 90% after 12 weeks
• Secukinumab: 80% after 12 weeks
• Ustekinumab: 70% after 12 weeks

There are a variety of factors to consider when determining which biologic to use for a psoriasis patient. These data may help in the decision process. However, dermatologists must educate psoriasis patients with a high body mass index that their disease may take longer to respond and may need combination therapy for optimal clearance.

Expert Commentary

All of the biologics, especially the IL-17 inhibitors, work very quickly to clear psoriasis. The only way they work “slowly” is that it may take time (usually a few days) for the payers to approve biologic prescriptions. 

—Jashin J. Wu, MD (Los Angeles, California)

Myth: Biologics Work Slowly

Biologics have demonstrated efficacy in psoriasis and often are used in psoriasis patients who have not achieved desired results with other treatments, patients who have had intolerable side effects from other treatments, and patients with concurrent diseases that preclude the use of systemic therapies. Because of the quality-of-life impact of psoriasis, patients look for quick clearance of their symptoms, but can biologics deliver fast results or do they work slowly?

Biologics such as etanercept and adalimumab block tumor necrosis factor α signaling, while ustekinumab targets IL-12 and IL-23 and others target IL-17. Some patients may begin to see improvement in skin lesions within 1 month of initiating biologic therapies because they target specific proinflammatory pathways that are critical to the pathogenesis of psoriasis, but response time varies among patients and specific therapy used.

The psoriasis area and severity index (PASI) measures psoriasis treatment success. Based on the American Academy of Dermatology’s guidelines of care for the management of psoriasis and psoriatic arthritis published in 2008, short-term response was achieved in 10 to 14 weeks for the following biologics:

• Adalimumab: 80% of patients achieved PASI 75 at week 12
• Etanercept: 49% of patients given 50 mg twice weekly achieved PASI 75 at 12 weeks; 34% of patients given 25 mg twice weekly achieved PASI 75 at 12 weeks
• Infliximab: 80% of patients achieved PASI 75 at week 10

Of the newer biologics, Premier Research recently noted that PASI 75 was achieved after 12 weeks with the following biologics:

• Brodalumab: 83% after 12 weeks
• Ixekizumab: 90% after 12 weeks
• Secukinumab: 80% after 12 weeks
• Ustekinumab: 70% after 12 weeks

There are a variety of factors to consider when determining which biologic to use for a psoriasis patient. These data may help in the decision process. However, dermatologists must educate psoriasis patients with a high body mass index that their disease may take longer to respond and may need combination therapy for optimal clearance.

Expert Commentary

All of the biologics, especially the IL-17 inhibitors, work very quickly to clear psoriasis. The only way they work “slowly” is that it may take time (usually a few days) for the payers to approve biologic prescriptions. 

—Jashin J. Wu, MD (Los Angeles, California)

Myth: Biologics Work Slowly

Biologics have demonstrated efficacy in psoriasis and often are used in psoriasis patients who have not achieved desired results with other treatments, patients who have had intolerable side effects from other treatments, and patients with concurrent diseases that preclude the use of systemic therapies. Because of the quality-of-life impact of psoriasis, patients look for quick clearance of their symptoms, but can biologics deliver fast results or do they work slowly?

Biologics such as etanercept and adalimumab block tumor necrosis factor α signaling, while ustekinumab targets IL-12 and IL-23 and others target IL-17. Some patients may begin to see improvement in skin lesions within 1 month of initiating biologic therapies because they target specific proinflammatory pathways that are critical to the pathogenesis of psoriasis, but response time varies among patients and specific therapy used.

The psoriasis area and severity index (PASI) measures psoriasis treatment success. Based on the American Academy of Dermatology’s guidelines of care for the management of psoriasis and psoriatic arthritis published in 2008, short-term response was achieved in 10 to 14 weeks for the following biologics:

• Adalimumab: 80% of patients achieved PASI 75 at week 12
• Etanercept: 49% of patients given 50 mg twice weekly achieved PASI 75 at 12 weeks; 34% of patients given 25 mg twice weekly achieved PASI 75 at 12 weeks
• Infliximab: 80% of patients achieved PASI 75 at week 10

Of the newer biologics, Premier Research recently noted that PASI 75 was achieved after 12 weeks with the following biologics:

• Brodalumab: 83% after 12 weeks
• Ixekizumab: 90% after 12 weeks
• Secukinumab: 80% after 12 weeks
• Ustekinumab: 70% after 12 weeks

There are a variety of factors to consider when determining which biologic to use for a psoriasis patient. These data may help in the decision process. However, dermatologists must educate psoriasis patients with a high body mass index that their disease may take longer to respond and may need combination therapy for optimal clearance.

Expert Commentary

All of the biologics, especially the IL-17 inhibitors, work very quickly to clear psoriasis. The only way they work “slowly” is that it may take time (usually a few days) for the payers to approve biologic prescriptions. 

—Jashin J. Wu, MD (Los Angeles, California)

If you were born in or after the 1970s, it is very likely that you have never watched a television show on a black and white set. Although the roots of its technology extend well back into the early 20th century, the first color broadcast on a national television network didn’t occur until 1954 with NBC’s coverage of the Tournament of Roses Parade.

When we compare the popularization of color television with the rapid pace at which we adopt new technology today, the popularization of color TV was glacial. In large part because of their expense, sales of color sets did not surpass black and white sets until 1972. Our family lagged behind the curve and finally caved in and junked our black and white television around 1977.

The observable change in our viewing behavior was dramatic. While programming in black and white was interesting, the color images were magnetic. We were drawn by the visual excitement and stimulation that color offered, and our family’s viewing standards took a precipitous dip. We seemed to watch anything that was colorful and moved. The quality of the content took a back seat. Viewing in color seemed to require much less cognitive effort. Ironically what attracted our attention allowed us to invest less energy in paying attention.

As a regular reader of Letters From Maine, you know that I am convinced that sleep deprivation is a major contributor to the emergence of the ADHD phenomenon. However, I can make a similar argument that the introduction of color television is an equally potent coconspirator or confounder. The magnetism inherent in a moving color image can tempt even the most health conscious among us to stay well past a brain-friendly bedtime. The invention of the electric light may have gotten the ball rolling, but the ubiquity of moving electronic color images has certainly greased what was already a very slippery slope into an abyss of unhealthy sleep habits.

©iStock/ThinkStockPhotos.com

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.”

If you were born in or after the 1970s, it is very likely that you have never watched a television show on a black and white set. Although the roots of its technology extend well back into the early 20th century, the first color broadcast on a national television network didn’t occur until 1954 with NBC’s coverage of the Tournament of Roses Parade.

When we compare the popularization of color television with the rapid pace at which we adopt new technology today, the popularization of color TV was glacial. In large part because of their expense, sales of color sets did not surpass black and white sets until 1972. Our family lagged behind the curve and finally caved in and junked our black and white television around 1977.

The observable change in our viewing behavior was dramatic. While programming in black and white was interesting, the color images were magnetic. We were drawn by the visual excitement and stimulation that color offered, and our family’s viewing standards took a precipitous dip. We seemed to watch anything that was colorful and moved. The quality of the content took a back seat. Viewing in color seemed to require much less cognitive effort. Ironically what attracted our attention allowed us to invest less energy in paying attention.

As a regular reader of Letters From Maine, you know that I am convinced that sleep deprivation is a major contributor to the emergence of the ADHD phenomenon. However, I can make a similar argument that the introduction of color television is an equally potent coconspirator or confounder. The magnetism inherent in a moving color image can tempt even the most health conscious among us to stay well past a brain-friendly bedtime. The invention of the electric light may have gotten the ball rolling, but the ubiquity of moving electronic color images has certainly greased what was already a very slippery slope into an abyss of unhealthy sleep habits.

©iStock/ThinkStockPhotos.com

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.”

If you were born in or after the 1970s, it is very likely that you have never watched a television show on a black and white set. Although the roots of its technology extend well back into the early 20th century, the first color broadcast on a national television network didn’t occur until 1954 with NBC’s coverage of the Tournament of Roses Parade.

When we compare the popularization of color television with the rapid pace at which we adopt new technology today, the popularization of color TV was glacial. In large part because of their expense, sales of color sets did not surpass black and white sets until 1972. Our family lagged behind the curve and finally caved in and junked our black and white television around 1977.

The observable change in our viewing behavior was dramatic. While programming in black and white was interesting, the color images were magnetic. We were drawn by the visual excitement and stimulation that color offered, and our family’s viewing standards took a precipitous dip. We seemed to watch anything that was colorful and moved. The quality of the content took a back seat. Viewing in color seemed to require much less cognitive effort. Ironically what attracted our attention allowed us to invest less energy in paying attention.

As a regular reader of Letters From Maine, you know that I am convinced that sleep deprivation is a major contributor to the emergence of the ADHD phenomenon. However, I can make a similar argument that the introduction of color television is an equally potent coconspirator or confounder. The magnetism inherent in a moving color image can tempt even the most health conscious among us to stay well past a brain-friendly bedtime. The invention of the electric light may have gotten the ball rolling, but the ubiquity of moving electronic color images has certainly greased what was already a very slippery slope into an abyss of unhealthy sleep habits.

©iStock/ThinkStockPhotos.com

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.”

ABSTRACT

The use of arthroscopy for purely diagnostic purposes has been largely supplanted by noninvasive technologies, such as magnetic resonance imaging (MRI). The mi-eye^+TM (Trice Medical) technology is a small-bore needle unit for in-office arthroscopy. We conducted a pilot study comparing the mi-eye^+TM unit with MRI, using surgical arthroscopy as a gold-standard reference. We hypothesized that the mi-eye^+TM needle arthroscope, which can be used in an office setting, would be equivalent to MRI for the diagnosis of intra-articular pathology of the knee.

This prospective, multicenter, observational study was approved by the Institutional Review Board. There were 106 patients (53 males, 53 females) in the study. MRIs were interpreted by musculoskeletally trained radiologists. The study was conducted in the operating room using the mi-eye^+TM device. The mi-eye^{+ TM} device findings were compared with the MRI findings within individual pathologies, and a “per-patient” analysis was performed to compare the arthroscopic findings with those of the mi-eye^+TM and the MRI. Additionally, we identified all mi-eye^+TM findings and MRI findings that exactly matched the surgical arthroscopy findings.

The mi-eye^+TM demonstrated complete accuracy of all pathologies for 97 (91.5%) of the 106 patients included in the study, whereas MRI demonstrated complete accuracy for 65 patients (61.3%) (P < .0001). All discrepancies between mi-eye^+TM and arthroscopy were false-negative mi-eye^+TM results, as the mi-eye^+TM did not reveal some aspect of the knee’s pathology for 9 patients. The mi-eye^+TM was more sensitive than MRI in identifying meniscal tears (92.6% vs 77.8%; P = .0035) and more specific in diagnosing these tears (100% vs 41.7%; P < .0001).

The mi-eye^+TM device proved to be more sensitive and specific than MRI for intra-articular findings at time of knee arthroscopy. Certainly there are contraindications to using the mi-eye^+TM, and our results do not obviate the need for MRI, but our study did demonstrate that the mi-eye^+TM needle arthroscope can safely provide excellent visualization of intra-articular knee pathology.

Continue to: Surgical arthroscopy is the gold standard...

Surgical arthroscopy is the gold standard for the diagnosis of intra-articular knee pathologies. Nevertheless, the use of arthroscopy for purely diagnostic purposes has been largely supplanted by noninvasive technologies, such as magnetic resonance imaging (MRI). Although MRI is considered the standard diagnostic tool for acute and chronic soft-tissue injuries of the knee, its use is not without contraindication and some potential inconveniences. Contraindications to MRI are well documented. In terms of inconvenience, MRI usually requires a separate visit followed by another visit to the prescribing physician. In addition, required interpretation by a radiologist may lead to a delay in care and increase in cost.

In the early 1990s, in-office needle arthroscopy was described as a viable means of diagnosing pathologies and obtaining synovial biopsies from the knee.^1-3 Initial results were good, and the procedures had very low complication rates. Nevertheless, in-office arthroscopy of the knee is not yet widely performed, likely given concerns about the technical difficulties of in-office arthroscopy, the potential for patient discomfort, and the cumbersomeness of in-office arthroscopy units. However, significant advances have been made in the resolution capability of small-bore needle arthroscopy, resulting in much less painful procedures. Additionally, the early hardware designs, which mimicked operating room setups using towers, fluid irrigation systems, and larger arthroscopes, have been replaced with small-needle arthroscopes that use syringes for irrigation and tablet computers for visualization (Figures 1A, 1B).  

The mi-eye^+TM technology (Trice Medical) is a small-bore needle unit for in-office arthroscopy with digital optics that does not need an irrigation tower. We conducted a pilot study of the sensitivity and specificity of the mi-eye^+TM unit in comparison with MRI, using surgical arthroscopy as a gold-standard reference. We hypothesized that the mi-eye^+TM needle arthroscope, which can be used in an office setting, would be equivalent to the standard of care (MRI) for the diagnosis of intra-articular pathology of the knee.

METHODS

Central regulatory approval for this prospective, multicenter, observational study was obtained from the Western Institutional Review Board for 3 of the sites, and 1 institution required and was granted internal Institutional Review Board approval.

The study was performed by 4 sports medicine orthopedic surgeons experienced in using the mi-eye^+TM in-office arthroscope. Patients were enrolled from December 2015 through June 2016. Inclusion criteria were an indication for an arthroscopic procedure of the knee based on history, physical examination, and MRI findings. Patients were excluded from the study if there were any contraindications to completing an MRI. Acute hemarthroses of the knee or active systemic infections were also excluded. Once a patient was identified as meeting the criteria for participation, informed consent was obtained. Of the 113 patients who enrolled, 7 did not have a complete study dataset available, leaving 106 patients (53 males, 53 females) in the study. Mean age was 47 years (range, 18-82 years).

Continue to: A test result form was used...

A test result form was used to record mi-eye^+TM, surgical arthroscopy, and MRI results. This form required a “positive” or “negative” result for all of several diagnoses: medial and lateral meniscal tears, intra-articular loose body, osteoarthritis (OA), osteochondritis dissecans (OCD), and tears of the anterior and posterior cruciate ligaments (ACL, PCL). MRI was performed at a variety of imaging facilities, but the images were interpreted by musculoskeletally trained radiologists.

The study was conducted in the operating room. After the patient was appropriately anesthetized, and the extremity prepared and draped, the mi-eye^+TM procedure was performed immediately prior to surgical arthroscopy. A tourniquet was not used. At surgeon discretion, medial, lateral, or both approaches were used with the mi-eye^+TM, and diagnostic arthroscopy was performed. During the procedure, the mi-eye^+TM was advanced into the knee. Once in the synovial compartment, the external 14-gauge needle was retracted, exposing the unit’s optics. Visualization was improved by injecting normal saline through the lure lock in the mi-eye^+TM needle arthroscope. An average of 20 mL of saline was used, though the amount varied with surgeon discretion. Subsequently, the surgeon visualized structures in the knee and documented all findings.

At the end of the mi-eye^+TM procedure, the scheduled surgical arthroscopy was performed. After the surgical procedure, if there were no issues or complications, the patient was discharged from the study. No follow-up was required for the study, as arthroscopic findings served as the conclusive diagnosis for each patient, and no interventions were being studied. There were no complications related to use of the mi-eye^+TM.

The mi-eye^+TM device findings were compared with the MRI findings within individual pathologies, and a “per-patient” analysis was performed to compare the arthroscopic findings with those of the mi-eye^+TM and the MRI. Additionally, we identified all mi-eye^+TM findings and MRI findings that exactly matched the surgical arthroscopy findings. When a test had no false-positive or false-negative findings in comparison with surgical arthroscopy, it was identified as having complete accuracy for all intra-articular knee pathologies. For these methods, the 95% confidence interval was determined based on binomial distribution.

RESULTS

The mi-eye^{+ TM} demonstrated complete accuracy of all pathologies for 97 (91.5%) of the 106 patients included in the study, whereas MRI demonstrated complete accuracy for 65 patients (61.3%) (P < .0001). All discrepancies between mi-eye^+TM and surgical arthroscopy were false-negative mi-eye^+TM results, as the mi-eye^+TM did not reveal some aspect of the knee’s pathology for 9 patients. On the other hand, MRI demonstrated both false-negative and false-positive results, failing to reveal some aspect of the knee’s pathology for 31 patients, and potentially overcalling some aspect of the knee’s pathology among 18 patients.

Continue to: The pathology most frequently...

The pathology most frequently identified in the study was a meniscal tear. The mi-eye^+TM was more sensitive than MRI in identifying meniscal tears (92.6% vs 77.8%; P = .0035) and more specific in diagnosing these tears (100% vs 87.5%; P < .0002). The difference in specificity resulted from the false MRI diagnosis of a meniscal tear among 24 patients, who were found to have no tear by both mi-eye^+TM and surgical arthroscopy.

Table 1. Raw Data of mi-eye^+TM and Magnetic Resonance Imaging Findings

The second most frequent pathology was an intra-articular loose body. The mi-eye^+TM was more sensitive than MRI in identifying loose bodies (86.7% vs 20%; P = .0007). The specificity of the mi-eye^+TM and the specificity of MRI were equivalent in diagnosing loose bodies (100%). Table 1 and Table 2 show the complete set of diagnoses and associated diagnostic profiles.

Table 2. Diagnostic Profiles: Sensitivity and Specificity of mi-eye^+TM and Magnetic Resonance Imaging

^aBold P values are significant. Abbreviations: CI, confidence interval; MRI, magnetic resonance imaging; N/A, not applicable.

DISCUSSION

The overall accuracy of the mi-eye^+TM was superior to that of MRI relative to the arthroscopic gold standard in this pilot study. Other studies have demonstrated the accuracy, feasibility, and cost-efficacy of in-office arthroscopy. However, likely because of the cumbersomeness of in-office arthroscopy equipment and the potential for patient discomfort, the technique is not yet standard in the field. Recent advances in small-bore technology, digital optics, and ergonomics have addressed the difficulties associated with in-office arthroscopy, facilitating a faster and more efficient procedure. Our goal in this study was to evaluate the diagnostic capability of the mi-eye^+TM in-office arthroscopy unit, which features a small bore, digital optics, and functionality without an irrigation tower.

This study of 106 patients demonstrated equivalent or better accuracy of the mi-eye^+TM relative to MRI when compared with the gold standard of surgical arthroscopy. This was not surprising given that both the mi-eye^+TM and surgical arthroscopy are based on direct visualization of intra-articular pathology. The mi-eye^+TM unit identified more meniscal tears, intra-articular loose bodies, ACL tears, and OCD lesions than MRI did, and with enough power to demonstrate statistically significant improved sensitivity for meniscal tears and loose bodies. Furthermore, MRI demonstrated false-positive meniscal tears, ACL tears, OCD lesions, and OA, whereas the mi-eye^+TM did not demonstrate any false-positive results in comparison with surgical arthroscopy. This study demonstrated statistically significant improved specificity of the mi-eye⁺ compared with MRI in the diagnosis of meniscal tears and OA.

There are several limitations to our study. We refer to it as a pilot study because it was performed in a standard operating room. Before taking the technology to an outpatient setting, we wanted to confirm efficacy and safety in an operating room. However, the techniques used in this study are readily transferable to the outpatient clinic setting and to date have been used in more than 2000 cases.

Continue to: The specificity of MRI...

The specificity of MRI for meniscal tears was unexpectedly low compared with previous studies, which may reflect the multi-institution, multi-surgeon, multi-radiologist involvement in MRI interpretation.^4-10 MRI was performed at a variety of institutions without a standardized protocol. This lack of standardization of image capture and interpretation may have contributed to the suboptimal performance of MRI, falsely decreasing the potential ideal specificity for meniscal tears. Although this study may have underestimated the specificity of MRI for meniscal tears, we think the mi-eye^+TM and MRI results reported here reflect the findings of standard practice, without the standardization usually applied in studies. For example, a study of 139 knee MRI reports at 14 different institutions confirmed arthroscopic findings and concluded that 37% of the operations supported by a significant MRI finding were unjustified.¹¹ The authors attributed the rate of false-positive MRI findings to the wide variety of places where patients had their MRIs performed, and the subsequent variation in quality of imaging and MRI reader skill level.¹¹

Before inserting the mi-eye^+TM needle arthroscope, the surgeons had a working diagnosis of the pathology based on their clinical examination and MRI results. Clearly, this introduced a bias. Further studies will be conducted in a prospective, blinded manner to address this limitation.

Although studies of in-office arthroscopy technology date to the 1990s, there is an overall lack of data comparing in-office arthroscopy with MRI. Halbrecht and Jackson² conducted a study of 20 knee patients with both MRI and in-office needle arthroscopy. Overall, MRI was poor in detecting cartilage defects, with sensitivity of 34.6%, using the in-office arthroscopy as the confirmatory diagnosis. Although the authors did not compare in-office diagnoses with surgical arthroscopic findings, they concluded that office arthroscopy is an accurate and cost-efficient alternative to MRI in diagnostic evaluation of knee patients. Xerogeanes and colleagues¹² studied 110 patients in a prospective, blinded, multicenter trial comparing a minimally invasive office-based arthroscopy with MRI, using surgical arthroscopy as the confirmatory diagnosis. They concluded that the office-based arthroscope was statistically equivalent to diagnostic surgical arthroscopy and that it outperformed MRI in helping make accurate diagnoses. The authors applied a cost analysis to their findings and determined that office-based arthroscopy could result in an annual potential savings of $177 million for the healthcare system.¹²

Modern imaging sequences on high-Tesla MRI machines provide excellent visualization. Nevertheless, a significant number of patients do not undergo MRI, owing to time constraints, contraindications, body habitus, or anxiety/claustrophobia. Our study results confirmed that doctors treating such patients now have a viable alternative to help diagnose pathology.

CONCLUSION

The mi-eye^+TM device proved to be more sensitive and specific than MRI for intra-articular findings at the time of knee arthroscopy. Certainly there are contraindications to using the mi-eye^+TM, and our results do not obviate the need for MRI; our study did demonstrate that the mi-eye^+TM needle arthroscope can safely provide excellent visualization of intra-articular knee pathology. More studies of the mi-eye^+TM device in a clinical setting are warranted.

ABSTRACT

The use of arthroscopy for purely diagnostic purposes has been largely supplanted by noninvasive technologies, such as magnetic resonance imaging (MRI). The mi-eye^+TM (Trice Medical) technology is a small-bore needle unit for in-office arthroscopy. We conducted a pilot study comparing the mi-eye^+TM unit with MRI, using surgical arthroscopy as a gold-standard reference. We hypothesized that the mi-eye^+TM needle arthroscope, which can be used in an office setting, would be equivalent to MRI for the diagnosis of intra-articular pathology of the knee.

This prospective, multicenter, observational study was approved by the Institutional Review Board. There were 106 patients (53 males, 53 females) in the study. MRIs were interpreted by musculoskeletally trained radiologists. The study was conducted in the operating room using the mi-eye^+TM device. The mi-eye^{+ TM} device findings were compared with the MRI findings within individual pathologies, and a “per-patient” analysis was performed to compare the arthroscopic findings with those of the mi-eye^+TM and the MRI. Additionally, we identified all mi-eye^+TM findings and MRI findings that exactly matched the surgical arthroscopy findings.

The mi-eye^+TM demonstrated complete accuracy of all pathologies for 97 (91.5%) of the 106 patients included in the study, whereas MRI demonstrated complete accuracy for 65 patients (61.3%) (P < .0001). All discrepancies between mi-eye^+TM and arthroscopy were false-negative mi-eye^+TM results, as the mi-eye^+TM did not reveal some aspect of the knee’s pathology for 9 patients. The mi-eye^+TM was more sensitive than MRI in identifying meniscal tears (92.6% vs 77.8%; P = .0035) and more specific in diagnosing these tears (100% vs 41.7%; P < .0001).

The mi-eye^+TM device proved to be more sensitive and specific than MRI for intra-articular findings at time of knee arthroscopy. Certainly there are contraindications to using the mi-eye^+TM, and our results do not obviate the need for MRI, but our study did demonstrate that the mi-eye^+TM needle arthroscope can safely provide excellent visualization of intra-articular knee pathology.

Continue to: Surgical arthroscopy is the gold standard...

Surgical arthroscopy is the gold standard for the diagnosis of intra-articular knee pathologies. Nevertheless, the use of arthroscopy for purely diagnostic purposes has been largely supplanted by noninvasive technologies, such as magnetic resonance imaging (MRI). Although MRI is considered the standard diagnostic tool for acute and chronic soft-tissue injuries of the knee, its use is not without contraindication and some potential inconveniences. Contraindications to MRI are well documented. In terms of inconvenience, MRI usually requires a separate visit followed by another visit to the prescribing physician. In addition, required interpretation by a radiologist may lead to a delay in care and increase in cost.

In the early 1990s, in-office needle arthroscopy was described as a viable means of diagnosing pathologies and obtaining synovial biopsies from the knee.^1-3 Initial results were good, and the procedures had very low complication rates. Nevertheless, in-office arthroscopy of the knee is not yet widely performed, likely given concerns about the technical difficulties of in-office arthroscopy, the potential for patient discomfort, and the cumbersomeness of in-office arthroscopy units. However, significant advances have been made in the resolution capability of small-bore needle arthroscopy, resulting in much less painful procedures. Additionally, the early hardware designs, which mimicked operating room setups using towers, fluid irrigation systems, and larger arthroscopes, have been replaced with small-needle arthroscopes that use syringes for irrigation and tablet computers for visualization (Figures 1A, 1B).  

The mi-eye^+TM technology (Trice Medical) is a small-bore needle unit for in-office arthroscopy with digital optics that does not need an irrigation tower. We conducted a pilot study of the sensitivity and specificity of the mi-eye^+TM unit in comparison with MRI, using surgical arthroscopy as a gold-standard reference. We hypothesized that the mi-eye^+TM needle arthroscope, which can be used in an office setting, would be equivalent to the standard of care (MRI) for the diagnosis of intra-articular pathology of the knee.

METHODS

Central regulatory approval for this prospective, multicenter, observational study was obtained from the Western Institutional Review Board for 3 of the sites, and 1 institution required and was granted internal Institutional Review Board approval.

The study was performed by 4 sports medicine orthopedic surgeons experienced in using the mi-eye^+TM in-office arthroscope. Patients were enrolled from December 2015 through June 2016. Inclusion criteria were an indication for an arthroscopic procedure of the knee based on history, physical examination, and MRI findings. Patients were excluded from the study if there were any contraindications to completing an MRI. Acute hemarthroses of the knee or active systemic infections were also excluded. Once a patient was identified as meeting the criteria for participation, informed consent was obtained. Of the 113 patients who enrolled, 7 did not have a complete study dataset available, leaving 106 patients (53 males, 53 females) in the study. Mean age was 47 years (range, 18-82 years).

Continue to: A test result form was used...

A test result form was used to record mi-eye^+TM, surgical arthroscopy, and MRI results. This form required a “positive” or “negative” result for all of several diagnoses: medial and lateral meniscal tears, intra-articular loose body, osteoarthritis (OA), osteochondritis dissecans (OCD), and tears of the anterior and posterior cruciate ligaments (ACL, PCL). MRI was performed at a variety of imaging facilities, but the images were interpreted by musculoskeletally trained radiologists.

The study was conducted in the operating room. After the patient was appropriately anesthetized, and the extremity prepared and draped, the mi-eye^+TM procedure was performed immediately prior to surgical arthroscopy. A tourniquet was not used. At surgeon discretion, medial, lateral, or both approaches were used with the mi-eye^+TM, and diagnostic arthroscopy was performed. During the procedure, the mi-eye^+TM was advanced into the knee. Once in the synovial compartment, the external 14-gauge needle was retracted, exposing the unit’s optics. Visualization was improved by injecting normal saline through the lure lock in the mi-eye^+TM needle arthroscope. An average of 20 mL of saline was used, though the amount varied with surgeon discretion. Subsequently, the surgeon visualized structures in the knee and documented all findings.

At the end of the mi-eye^+TM procedure, the scheduled surgical arthroscopy was performed. After the surgical procedure, if there were no issues or complications, the patient was discharged from the study. No follow-up was required for the study, as arthroscopic findings served as the conclusive diagnosis for each patient, and no interventions were being studied. There were no complications related to use of the mi-eye^+TM.

The mi-eye^+TM device findings were compared with the MRI findings within individual pathologies, and a “per-patient” analysis was performed to compare the arthroscopic findings with those of the mi-eye^+TM and the MRI. Additionally, we identified all mi-eye^+TM findings and MRI findings that exactly matched the surgical arthroscopy findings. When a test had no false-positive or false-negative findings in comparison with surgical arthroscopy, it was identified as having complete accuracy for all intra-articular knee pathologies. For these methods, the 95% confidence interval was determined based on binomial distribution.

RESULTS

The mi-eye^{+ TM} demonstrated complete accuracy of all pathologies for 97 (91.5%) of the 106 patients included in the study, whereas MRI demonstrated complete accuracy for 65 patients (61.3%) (P < .0001). All discrepancies between mi-eye^+TM and surgical arthroscopy were false-negative mi-eye^+TM results, as the mi-eye^+TM did not reveal some aspect of the knee’s pathology for 9 patients. On the other hand, MRI demonstrated both false-negative and false-positive results, failing to reveal some aspect of the knee’s pathology for 31 patients, and potentially overcalling some aspect of the knee’s pathology among 18 patients.

Continue to: The pathology most frequently...

The pathology most frequently identified in the study was a meniscal tear. The mi-eye^+TM was more sensitive than MRI in identifying meniscal tears (92.6% vs 77.8%; P = .0035) and more specific in diagnosing these tears (100% vs 87.5%; P < .0002). The difference in specificity resulted from the false MRI diagnosis of a meniscal tear among 24 patients, who were found to have no tear by both mi-eye^+TM and surgical arthroscopy.

Table 1. Raw Data of mi-eye^+TM and Magnetic Resonance Imaging Findings

The second most frequent pathology was an intra-articular loose body. The mi-eye^+TM was more sensitive than MRI in identifying loose bodies (86.7% vs 20%; P = .0007). The specificity of the mi-eye^+TM and the specificity of MRI were equivalent in diagnosing loose bodies (100%). Table 1 and Table 2 show the complete set of diagnoses and associated diagnostic profiles.

Table 2. Diagnostic Profiles: Sensitivity and Specificity of mi-eye^+TM and Magnetic Resonance Imaging

^aBold P values are significant. Abbreviations: CI, confidence interval; MRI, magnetic resonance imaging; N/A, not applicable.

DISCUSSION

The overall accuracy of the mi-eye^+TM was superior to that of MRI relative to the arthroscopic gold standard in this pilot study. Other studies have demonstrated the accuracy, feasibility, and cost-efficacy of in-office arthroscopy. However, likely because of the cumbersomeness of in-office arthroscopy equipment and the potential for patient discomfort, the technique is not yet standard in the field. Recent advances in small-bore technology, digital optics, and ergonomics have addressed the difficulties associated with in-office arthroscopy, facilitating a faster and more efficient procedure. Our goal in this study was to evaluate the diagnostic capability of the mi-eye^+TM in-office arthroscopy unit, which features a small bore, digital optics, and functionality without an irrigation tower.

This study of 106 patients demonstrated equivalent or better accuracy of the mi-eye^+TM relative to MRI when compared with the gold standard of surgical arthroscopy. This was not surprising given that both the mi-eye^+TM and surgical arthroscopy are based on direct visualization of intra-articular pathology. The mi-eye^+TM unit identified more meniscal tears, intra-articular loose bodies, ACL tears, and OCD lesions than MRI did, and with enough power to demonstrate statistically significant improved sensitivity for meniscal tears and loose bodies. Furthermore, MRI demonstrated false-positive meniscal tears, ACL tears, OCD lesions, and OA, whereas the mi-eye^+TM did not demonstrate any false-positive results in comparison with surgical arthroscopy. This study demonstrated statistically significant improved specificity of the mi-eye⁺ compared with MRI in the diagnosis of meniscal tears and OA.

There are several limitations to our study. We refer to it as a pilot study because it was performed in a standard operating room. Before taking the technology to an outpatient setting, we wanted to confirm efficacy and safety in an operating room. However, the techniques used in this study are readily transferable to the outpatient clinic setting and to date have been used in more than 2000 cases.

Continue to: The specificity of MRI...

The specificity of MRI for meniscal tears was unexpectedly low compared with previous studies, which may reflect the multi-institution, multi-surgeon, multi-radiologist involvement in MRI interpretation.^4-10 MRI was performed at a variety of institutions without a standardized protocol. This lack of standardization of image capture and interpretation may have contributed to the suboptimal performance of MRI, falsely decreasing the potential ideal specificity for meniscal tears. Although this study may have underestimated the specificity of MRI for meniscal tears, we think the mi-eye^+TM and MRI results reported here reflect the findings of standard practice, without the standardization usually applied in studies. For example, a study of 139 knee MRI reports at 14 different institutions confirmed arthroscopic findings and concluded that 37% of the operations supported by a significant MRI finding were unjustified.¹¹ The authors attributed the rate of false-positive MRI findings to the wide variety of places where patients had their MRIs performed, and the subsequent variation in quality of imaging and MRI reader skill level.¹¹

Before inserting the mi-eye^+TM needle arthroscope, the surgeons had a working diagnosis of the pathology based on their clinical examination and MRI results. Clearly, this introduced a bias. Further studies will be conducted in a prospective, blinded manner to address this limitation.

Although studies of in-office arthroscopy technology date to the 1990s, there is an overall lack of data comparing in-office arthroscopy with MRI. Halbrecht and Jackson² conducted a study of 20 knee patients with both MRI and in-office needle arthroscopy. Overall, MRI was poor in detecting cartilage defects, with sensitivity of 34.6%, using the in-office arthroscopy as the confirmatory diagnosis. Although the authors did not compare in-office diagnoses with surgical arthroscopic findings, they concluded that office arthroscopy is an accurate and cost-efficient alternative to MRI in diagnostic evaluation of knee patients. Xerogeanes and colleagues¹² studied 110 patients in a prospective, blinded, multicenter trial comparing a minimally invasive office-based arthroscopy with MRI, using surgical arthroscopy as the confirmatory diagnosis. They concluded that the office-based arthroscope was statistically equivalent to diagnostic surgical arthroscopy and that it outperformed MRI in helping make accurate diagnoses. The authors applied a cost analysis to their findings and determined that office-based arthroscopy could result in an annual potential savings of $177 million for the healthcare system.¹²

Modern imaging sequences on high-Tesla MRI machines provide excellent visualization. Nevertheless, a significant number of patients do not undergo MRI, owing to time constraints, contraindications, body habitus, or anxiety/claustrophobia. Our study results confirmed that doctors treating such patients now have a viable alternative to help diagnose pathology.

CONCLUSION

The mi-eye^+TM device proved to be more sensitive and specific than MRI for intra-articular findings at the time of knee arthroscopy. Certainly there are contraindications to using the mi-eye^+TM, and our results do not obviate the need for MRI; our study did demonstrate that the mi-eye^+TM needle arthroscope can safely provide excellent visualization of intra-articular knee pathology. More studies of the mi-eye^+TM device in a clinical setting are warranted.

ABSTRACT

The use of arthroscopy for purely diagnostic purposes has been largely supplanted by noninvasive technologies, such as magnetic resonance imaging (MRI). The mi-eye^+TM (Trice Medical) technology is a small-bore needle unit for in-office arthroscopy. We conducted a pilot study comparing the mi-eye^+TM unit with MRI, using surgical arthroscopy as a gold-standard reference. We hypothesized that the mi-eye^+TM needle arthroscope, which can be used in an office setting, would be equivalent to MRI for the diagnosis of intra-articular pathology of the knee.

This prospective, multicenter, observational study was approved by the Institutional Review Board. There were 106 patients (53 males, 53 females) in the study. MRIs were interpreted by musculoskeletally trained radiologists. The study was conducted in the operating room using the mi-eye^+TM device. The mi-eye^{+ TM} device findings were compared with the MRI findings within individual pathologies, and a “per-patient” analysis was performed to compare the arthroscopic findings with those of the mi-eye^+TM and the MRI. Additionally, we identified all mi-eye^+TM findings and MRI findings that exactly matched the surgical arthroscopy findings.

The mi-eye^+TM demonstrated complete accuracy of all pathologies for 97 (91.5%) of the 106 patients included in the study, whereas MRI demonstrated complete accuracy for 65 patients (61.3%) (P < .0001). All discrepancies between mi-eye^+TM and arthroscopy were false-negative mi-eye^+TM results, as the mi-eye^+TM did not reveal some aspect of the knee’s pathology for 9 patients. The mi-eye^+TM was more sensitive than MRI in identifying meniscal tears (92.6% vs 77.8%; P = .0035) and more specific in diagnosing these tears (100% vs 41.7%; P < .0001).

The mi-eye^+TM device proved to be more sensitive and specific than MRI for intra-articular findings at time of knee arthroscopy. Certainly there are contraindications to using the mi-eye^+TM, and our results do not obviate the need for MRI, but our study did demonstrate that the mi-eye^+TM needle arthroscope can safely provide excellent visualization of intra-articular knee pathology.

Continue to: Surgical arthroscopy is the gold standard...

Surgical arthroscopy is the gold standard for the diagnosis of intra-articular knee pathologies. Nevertheless, the use of arthroscopy for purely diagnostic purposes has been largely supplanted by noninvasive technologies, such as magnetic resonance imaging (MRI). Although MRI is considered the standard diagnostic tool for acute and chronic soft-tissue injuries of the knee, its use is not without contraindication and some potential inconveniences. Contraindications to MRI are well documented. In terms of inconvenience, MRI usually requires a separate visit followed by another visit to the prescribing physician. In addition, required interpretation by a radiologist may lead to a delay in care and increase in cost.

In the early 1990s, in-office needle arthroscopy was described as a viable means of diagnosing pathologies and obtaining synovial biopsies from the knee.^1-3 Initial results were good, and the procedures had very low complication rates. Nevertheless, in-office arthroscopy of the knee is not yet widely performed, likely given concerns about the technical difficulties of in-office arthroscopy, the potential for patient discomfort, and the cumbersomeness of in-office arthroscopy units. However, significant advances have been made in the resolution capability of small-bore needle arthroscopy, resulting in much less painful procedures. Additionally, the early hardware designs, which mimicked operating room setups using towers, fluid irrigation systems, and larger arthroscopes, have been replaced with small-needle arthroscopes that use syringes for irrigation and tablet computers for visualization (Figures 1A, 1B).  

The mi-eye^+TM technology (Trice Medical) is a small-bore needle unit for in-office arthroscopy with digital optics that does not need an irrigation tower. We conducted a pilot study of the sensitivity and specificity of the mi-eye^+TM unit in comparison with MRI, using surgical arthroscopy as a gold-standard reference. We hypothesized that the mi-eye^+TM needle arthroscope, which can be used in an office setting, would be equivalent to the standard of care (MRI) for the diagnosis of intra-articular pathology of the knee.

METHODS

Central regulatory approval for this prospective, multicenter, observational study was obtained from the Western Institutional Review Board for 3 of the sites, and 1 institution required and was granted internal Institutional Review Board approval.

The study was performed by 4 sports medicine orthopedic surgeons experienced in using the mi-eye^+TM in-office arthroscope. Patients were enrolled from December 2015 through June 2016. Inclusion criteria were an indication for an arthroscopic procedure of the knee based on history, physical examination, and MRI findings. Patients were excluded from the study if there were any contraindications to completing an MRI. Acute hemarthroses of the knee or active systemic infections were also excluded. Once a patient was identified as meeting the criteria for participation, informed consent was obtained. Of the 113 patients who enrolled, 7 did not have a complete study dataset available, leaving 106 patients (53 males, 53 females) in the study. Mean age was 47 years (range, 18-82 years).

Continue to: A test result form was used...

A test result form was used to record mi-eye^+TM, surgical arthroscopy, and MRI results. This form required a “positive” or “negative” result for all of several diagnoses: medial and lateral meniscal tears, intra-articular loose body, osteoarthritis (OA), osteochondritis dissecans (OCD), and tears of the anterior and posterior cruciate ligaments (ACL, PCL). MRI was performed at a variety of imaging facilities, but the images were interpreted by musculoskeletally trained radiologists.

The study was conducted in the operating room. After the patient was appropriately anesthetized, and the extremity prepared and draped, the mi-eye^+TM procedure was performed immediately prior to surgical arthroscopy. A tourniquet was not used. At surgeon discretion, medial, lateral, or both approaches were used with the mi-eye^+TM, and diagnostic arthroscopy was performed. During the procedure, the mi-eye^+TM was advanced into the knee. Once in the synovial compartment, the external 14-gauge needle was retracted, exposing the unit’s optics. Visualization was improved by injecting normal saline through the lure lock in the mi-eye^+TM needle arthroscope. An average of 20 mL of saline was used, though the amount varied with surgeon discretion. Subsequently, the surgeon visualized structures in the knee and documented all findings.

At the end of the mi-eye^+TM procedure, the scheduled surgical arthroscopy was performed. After the surgical procedure, if there were no issues or complications, the patient was discharged from the study. No follow-up was required for the study, as arthroscopic findings served as the conclusive diagnosis for each patient, and no interventions were being studied. There were no complications related to use of the mi-eye^+TM.

The mi-eye^+TM device findings were compared with the MRI findings within individual pathologies, and a “per-patient” analysis was performed to compare the arthroscopic findings with those of the mi-eye^+TM and the MRI. Additionally, we identified all mi-eye^+TM findings and MRI findings that exactly matched the surgical arthroscopy findings. When a test had no false-positive or false-negative findings in comparison with surgical arthroscopy, it was identified as having complete accuracy for all intra-articular knee pathologies. For these methods, the 95% confidence interval was determined based on binomial distribution.

RESULTS

The mi-eye^{+ TM} demonstrated complete accuracy of all pathologies for 97 (91.5%) of the 106 patients included in the study, whereas MRI demonstrated complete accuracy for 65 patients (61.3%) (P < .0001). All discrepancies between mi-eye^+TM and surgical arthroscopy were false-negative mi-eye^+TM results, as the mi-eye^+TM did not reveal some aspect of the knee’s pathology for 9 patients. On the other hand, MRI demonstrated both false-negative and false-positive results, failing to reveal some aspect of the knee’s pathology for 31 patients, and potentially overcalling some aspect of the knee’s pathology among 18 patients.

Continue to: The pathology most frequently...

The pathology most frequently identified in the study was a meniscal tear. The mi-eye^+TM was more sensitive than MRI in identifying meniscal tears (92.6% vs 77.8%; P = .0035) and more specific in diagnosing these tears (100% vs 87.5%; P < .0002). The difference in specificity resulted from the false MRI diagnosis of a meniscal tear among 24 patients, who were found to have no tear by both mi-eye^+TM and surgical arthroscopy.

Table 1. Raw Data of mi-eye^+TM and Magnetic Resonance Imaging Findings

The second most frequent pathology was an intra-articular loose body. The mi-eye^+TM was more sensitive than MRI in identifying loose bodies (86.7% vs 20%; P = .0007). The specificity of the mi-eye^+TM and the specificity of MRI were equivalent in diagnosing loose bodies (100%). Table 1 and Table 2 show the complete set of diagnoses and associated diagnostic profiles.

Table 2. Diagnostic Profiles: Sensitivity and Specificity of mi-eye^+TM and Magnetic Resonance Imaging

^aBold P values are significant. Abbreviations: CI, confidence interval; MRI, magnetic resonance imaging; N/A, not applicable.

DISCUSSION

The overall accuracy of the mi-eye^+TM was superior to that of MRI relative to the arthroscopic gold standard in this pilot study. Other studies have demonstrated the accuracy, feasibility, and cost-efficacy of in-office arthroscopy. However, likely because of the cumbersomeness of in-office arthroscopy equipment and the potential for patient discomfort, the technique is not yet standard in the field. Recent advances in small-bore technology, digital optics, and ergonomics have addressed the difficulties associated with in-office arthroscopy, facilitating a faster and more efficient procedure. Our goal in this study was to evaluate the diagnostic capability of the mi-eye^+TM in-office arthroscopy unit, which features a small bore, digital optics, and functionality without an irrigation tower.

This study of 106 patients demonstrated equivalent or better accuracy of the mi-eye^+TM relative to MRI when compared with the gold standard of surgical arthroscopy. This was not surprising given that both the mi-eye^+TM and surgical arthroscopy are based on direct visualization of intra-articular pathology. The mi-eye^+TM unit identified more meniscal tears, intra-articular loose bodies, ACL tears, and OCD lesions than MRI did, and with enough power to demonstrate statistically significant improved sensitivity for meniscal tears and loose bodies. Furthermore, MRI demonstrated false-positive meniscal tears, ACL tears, OCD lesions, and OA, whereas the mi-eye^+TM did not demonstrate any false-positive results in comparison with surgical arthroscopy. This study demonstrated statistically significant improved specificity of the mi-eye⁺ compared with MRI in the diagnosis of meniscal tears and OA.

There are several limitations to our study. We refer to it as a pilot study because it was performed in a standard operating room. Before taking the technology to an outpatient setting, we wanted to confirm efficacy and safety in an operating room. However, the techniques used in this study are readily transferable to the outpatient clinic setting and to date have been used in more than 2000 cases.

Continue to: The specificity of MRI...

The specificity of MRI for meniscal tears was unexpectedly low compared with previous studies, which may reflect the multi-institution, multi-surgeon, multi-radiologist involvement in MRI interpretation.^4-10 MRI was performed at a variety of institutions without a standardized protocol. This lack of standardization of image capture and interpretation may have contributed to the suboptimal performance of MRI, falsely decreasing the potential ideal specificity for meniscal tears. Although this study may have underestimated the specificity of MRI for meniscal tears, we think the mi-eye^+TM and MRI results reported here reflect the findings of standard practice, without the standardization usually applied in studies. For example, a study of 139 knee MRI reports at 14 different institutions confirmed arthroscopic findings and concluded that 37% of the operations supported by a significant MRI finding were unjustified.¹¹ The authors attributed the rate of false-positive MRI findings to the wide variety of places where patients had their MRIs performed, and the subsequent variation in quality of imaging and MRI reader skill level.¹¹

Before inserting the mi-eye^+TM needle arthroscope, the surgeons had a working diagnosis of the pathology based on their clinical examination and MRI results. Clearly, this introduced a bias. Further studies will be conducted in a prospective, blinded manner to address this limitation.

Although studies of in-office arthroscopy technology date to the 1990s, there is an overall lack of data comparing in-office arthroscopy with MRI. Halbrecht and Jackson² conducted a study of 20 knee patients with both MRI and in-office needle arthroscopy. Overall, MRI was poor in detecting cartilage defects, with sensitivity of 34.6%, using the in-office arthroscopy as the confirmatory diagnosis. Although the authors did not compare in-office diagnoses with surgical arthroscopic findings, they concluded that office arthroscopy is an accurate and cost-efficient alternative to MRI in diagnostic evaluation of knee patients. Xerogeanes and colleagues¹² studied 110 patients in a prospective, blinded, multicenter trial comparing a minimally invasive office-based arthroscopy with MRI, using surgical arthroscopy as the confirmatory diagnosis. They concluded that the office-based arthroscope was statistically equivalent to diagnostic surgical arthroscopy and that it outperformed MRI in helping make accurate diagnoses. The authors applied a cost analysis to their findings and determined that office-based arthroscopy could result in an annual potential savings of $177 million for the healthcare system.¹²

Modern imaging sequences on high-Tesla MRI machines provide excellent visualization. Nevertheless, a significant number of patients do not undergo MRI, owing to time constraints, contraindications, body habitus, or anxiety/claustrophobia. Our study results confirmed that doctors treating such patients now have a viable alternative to help diagnose pathology.

CONCLUSION

The mi-eye^+TM device proved to be more sensitive and specific than MRI for intra-articular findings at the time of knee arthroscopy. Certainly there are contraindications to using the mi-eye^+TM, and our results do not obviate the need for MRI; our study did demonstrate that the mi-eye^+TM needle arthroscope can safely provide excellent visualization of intra-articular knee pathology. More studies of the mi-eye^+TM device in a clinical setting are warranted.

Serotonin syndrome (SS) is diagnosed by the clinical triad of dysautonomia (fever, mydriasis, diaphoresis, tachycardia), neuromuscular signs (ataxia, hyperreflexia, tremor, myoclonus), and altered mental status (seizures, delirium). Two validated criteria groups are accepted, the Hunter criteria and the Sternbach criteria. These criteria require a menu-like approach of clinical manifestations of the above signs with known addition or increase of a serotonergic medication and the absence of other possible causes, such as neuroleptics.

In 2006, the FDA issued a clinical warning titled “Potentially Life-Threatening Serotonin Syndrome With Combined Use of SSRIs or SNRIs and Triptan Medications.” Subsequently, Randolph W. Evans, MD, and others conducted a close evaluation of the cases used by the FDA as the basis for their warning. They noted that none of the initial cases met Hunter criteria, only 10 of 29 met Sternbach criteria, and a second set of 11 patients also were questionable in terms of the diagnosis of serotonin toxicity. Serotonin (5-HT) toxicity is mediated by excessive activity of 5-HT_2A receptors, and triptans have no action at those receptors, only having activity at 5-HT_1B, _1D, and _1F receptors.

In 2010, the American Headache Society (AHS) published a position paper on this drug-drug interaction. In it, they stated, “with only Class IV evidence available in the literature and available through the FDA registration of adverse events, …the currently available evidence does not support limiting the use of triptans with SSRIs or SNRIs, or the use of triptan monotherapy, due to concerns for serotonin syndrome (Level U).”

Confirming the lack of evidence for an interaction, Dr. Yulia Orlova from the Graham Headache Center in Boston reported from the Partners Healthcare System Research Patient Data Registry on about 48,000 patients prescribed triptans, of whom about 19,000 were also co-prescribed SSRI or SNRI antidepressants. None of the cases met Hunter and Sternbach criteria and one patient who manifested serotonin toxicity had signs that preceded triptan use.  A previous trial of a cohort of 240,268 patients receiving pharmacy benefits reported that the frequency of co-prescription of triptans with SSRIs was about 20%. With the size of these reports, the absence of documented cases fulfilling both sets of criteria, and the lack of receptor plausibility as a cause for serotonin toxicity from triptans, the likelihood of the syndrome from triptan use is low, and the warning inappropriate. The co-occurrence of depression, anxiety, and migraine often makes co-prescription of triptans and antidepressants necessary, and the concern for co-prescription excessive.

—Stewart J. Tepper, MD
Professor of Neurology
Geisel School of Medicine at Dartmouth

Serotonin syndrome (SS) is diagnosed by the clinical triad of dysautonomia (fever, mydriasis, diaphoresis, tachycardia), neuromuscular signs (ataxia, hyperreflexia, tremor, myoclonus), and altered mental status (seizures, delirium). Two validated criteria groups are accepted, the Hunter criteria and the Sternbach criteria. These criteria require a menu-like approach of clinical manifestations of the above signs with known addition or increase of a serotonergic medication and the absence of other possible causes, such as neuroleptics.

In 2006, the FDA issued a clinical warning titled “Potentially Life-Threatening Serotonin Syndrome With Combined Use of SSRIs or SNRIs and Triptan Medications.” Subsequently, Randolph W. Evans, MD, and others conducted a close evaluation of the cases used by the FDA as the basis for their warning. They noted that none of the initial cases met Hunter criteria, only 10 of 29 met Sternbach criteria, and a second set of 11 patients also were questionable in terms of the diagnosis of serotonin toxicity. Serotonin (5-HT) toxicity is mediated by excessive activity of 5-HT_2A receptors, and triptans have no action at those receptors, only having activity at 5-HT_1B, _1D, and _1F receptors.

In 2010, the American Headache Society (AHS) published a position paper on this drug-drug interaction. In it, they stated, “with only Class IV evidence available in the literature and available through the FDA registration of adverse events, …the currently available evidence does not support limiting the use of triptans with SSRIs or SNRIs, or the use of triptan monotherapy, due to concerns for serotonin syndrome (Level U).”

Confirming the lack of evidence for an interaction, Dr. Yulia Orlova from the Graham Headache Center in Boston reported from the Partners Healthcare System Research Patient Data Registry on about 48,000 patients prescribed triptans, of whom about 19,000 were also co-prescribed SSRI or SNRI antidepressants. None of the cases met Hunter and Sternbach criteria and one patient who manifested serotonin toxicity had signs that preceded triptan use.  A previous trial of a cohort of 240,268 patients receiving pharmacy benefits reported that the frequency of co-prescription of triptans with SSRIs was about 20%. With the size of these reports, the absence of documented cases fulfilling both sets of criteria, and the lack of receptor plausibility as a cause for serotonin toxicity from triptans, the likelihood of the syndrome from triptan use is low, and the warning inappropriate. The co-occurrence of depression, anxiety, and migraine often makes co-prescription of triptans and antidepressants necessary, and the concern for co-prescription excessive.

—Stewart J. Tepper, MD
Professor of Neurology
Geisel School of Medicine at Dartmouth

Serotonin syndrome (SS) is diagnosed by the clinical triad of dysautonomia (fever, mydriasis, diaphoresis, tachycardia), neuromuscular signs (ataxia, hyperreflexia, tremor, myoclonus), and altered mental status (seizures, delirium). Two validated criteria groups are accepted, the Hunter criteria and the Sternbach criteria. These criteria require a menu-like approach of clinical manifestations of the above signs with known addition or increase of a serotonergic medication and the absence of other possible causes, such as neuroleptics.

In 2006, the FDA issued a clinical warning titled “Potentially Life-Threatening Serotonin Syndrome With Combined Use of SSRIs or SNRIs and Triptan Medications.” Subsequently, Randolph W. Evans, MD, and others conducted a close evaluation of the cases used by the FDA as the basis for their warning. They noted that none of the initial cases met Hunter criteria, only 10 of 29 met Sternbach criteria, and a second set of 11 patients also were questionable in terms of the diagnosis of serotonin toxicity. Serotonin (5-HT) toxicity is mediated by excessive activity of 5-HT_2A receptors, and triptans have no action at those receptors, only having activity at 5-HT_1B, _1D, and _1F receptors.

In 2010, the American Headache Society (AHS) published a position paper on this drug-drug interaction. In it, they stated, “with only Class IV evidence available in the literature and available through the FDA registration of adverse events, …the currently available evidence does not support limiting the use of triptans with SSRIs or SNRIs, or the use of triptan monotherapy, due to concerns for serotonin syndrome (Level U).”

Confirming the lack of evidence for an interaction, Dr. Yulia Orlova from the Graham Headache Center in Boston reported from the Partners Healthcare System Research Patient Data Registry on about 48,000 patients prescribed triptans, of whom about 19,000 were also co-prescribed SSRI or SNRI antidepressants. None of the cases met Hunter and Sternbach criteria and one patient who manifested serotonin toxicity had signs that preceded triptan use.  A previous trial of a cohort of 240,268 patients receiving pharmacy benefits reported that the frequency of co-prescription of triptans with SSRIs was about 20%. With the size of these reports, the absence of documented cases fulfilling both sets of criteria, and the lack of receptor plausibility as a cause for serotonin toxicity from triptans, the likelihood of the syndrome from triptan use is low, and the warning inappropriate. The co-occurrence of depression, anxiety, and migraine often makes co-prescription of triptans and antidepressants necessary, and the concern for co-prescription excessive.

—Stewart J. Tepper, MD
Professor of Neurology
Geisel School of Medicine at Dartmouth

LOS ANGELES – The benefits of mechanical thrombectomy observed in the DAWN trial for patients with acute ischemic stroke and a mismatch between core imaging and clinical presentation out to 24 hours appear to apply regardless of whether their eligibility is determined by CT perfusion or diffusion-weighted magnetic resonance imaging, according to a subanalysis of the trial data.

Diffusion-weighted magnetic resonance imaging (DW-MRI) is considered the gold standard, but it is not as widely available as CT perfusion (CTP) and previous studies have shown that MR is associated with longer times between stroke onset and treatment randomization. “Though MR was originally preferred in DAWN, it was pretty clear that CT perfusion was going to need to be employed in the trial as well,” Cathy Sila, MD, said during her presentation of the results of the subanalysis at the International Stroke Conference 2018, sponsored by the American Heart Association.

The research sought to determine if the two imaging methods perform similarly. CTP is more readily available, but it has some issues. In patients with severe heart failure, a severe proximal stenosis, or a contralateral severe stenosis, the technique may struggle to accurately image the core infarct, which has led some to wonder if the outcomes would be as good using CTP as selection criteria. “In our institution, we’ve had this conversation very frequently,” said Dr. Sila, who is a vascular neurologist and the director of the University Hospitals Systems stroke program in Cleveland.

To be eligible for DAWN, the core infarct had to correspond to at least a 30% decrease in regional blood flow in the CTP map, or an apparent diffusion coefficient of less than 620 on DW-MRI.

The researchers included all 206 patients in the DAWN study (N Engl J Med. 2018;378:11-21), separating them into DW-MRI or CTP groups based on which imaging method was used to randomize them during the trial. There were no statistically significant differences in any of the baseline characteristics between the two imaging groups.

The 26 sites participating in DAWN had clear differences in their preferences for imaging techniques; 19 exclusively used CTP, 4 used only DW-MRI, and 3 sites used a combination of both imaging methods.

There were no statistically significant differences between the two groups in any of the measured clinical outcomes, including neurologic deterioration in hospital (22.8% with CTP vs. 15.7% with DW-MRII, P = .286), symptomatic intracranial hemorrhage (4.1% with CTP vs. 4.8% with DW-MRI, P = 1.000), or death related to stroke (19.5% with CTP vs. 13.3% with DW-MRI, P = .263). Outcomes at 90 days proved to be similar between CTP and DW-MRI for achieving functional independence (29.3% vs. 34.9%, respectively; P = .445) and utility-weighted modified Rankin Scale scores (4.2 vs. 4.9, respectively; P = .172).

Multivariate analyses showed that 90-day functional independence was predicted by thrombectomy treatment, age, blood glucose level, baseline National Institutes of Health Stroke Scale score, and core lab ASPECTS (Alberta Stroke Program Early CT Score), but not the method of imaging.

“The efficacy and safety of mechanical thrombectomy for patients meeting those clinical mismatch criteria at 6-24 hours were comparable whether the small core infarcts were measured by diffusion imaging or cerebral blood flow imaging. I believe that future clinical trials aiming to extend the eligibility outside of this prespecified population should include both imaging modalities to determine whether these results are generalizable,” Dr. Sila said.

The DAWN study was funded by Stryker Neurovascular. Dr. Sila has reported receiving honoraria from Medtronic.

SOURCE: Sila C et al. ISC 2018, abstract LB11.

LOS ANGELES – The benefits of mechanical thrombectomy observed in the DAWN trial for patients with acute ischemic stroke and a mismatch between core imaging and clinical presentation out to 24 hours appear to apply regardless of whether their eligibility is determined by CT perfusion or diffusion-weighted magnetic resonance imaging, according to a subanalysis of the trial data.

Diffusion-weighted magnetic resonance imaging (DW-MRI) is considered the gold standard, but it is not as widely available as CT perfusion (CTP) and previous studies have shown that MR is associated with longer times between stroke onset and treatment randomization. “Though MR was originally preferred in DAWN, it was pretty clear that CT perfusion was going to need to be employed in the trial as well,” Cathy Sila, MD, said during her presentation of the results of the subanalysis at the International Stroke Conference 2018, sponsored by the American Heart Association.

The research sought to determine if the two imaging methods perform similarly. CTP is more readily available, but it has some issues. In patients with severe heart failure, a severe proximal stenosis, or a contralateral severe stenosis, the technique may struggle to accurately image the core infarct, which has led some to wonder if the outcomes would be as good using CTP as selection criteria. “In our institution, we’ve had this conversation very frequently,” said Dr. Sila, who is a vascular neurologist and the director of the University Hospitals Systems stroke program in Cleveland.

To be eligible for DAWN, the core infarct had to correspond to at least a 30% decrease in regional blood flow in the CTP map, or an apparent diffusion coefficient of less than 620 on DW-MRI.

The researchers included all 206 patients in the DAWN study (N Engl J Med. 2018;378:11-21), separating them into DW-MRI or CTP groups based on which imaging method was used to randomize them during the trial. There were no statistically significant differences in any of the baseline characteristics between the two imaging groups.

The 26 sites participating in DAWN had clear differences in their preferences for imaging techniques; 19 exclusively used CTP, 4 used only DW-MRI, and 3 sites used a combination of both imaging methods.

There were no statistically significant differences between the two groups in any of the measured clinical outcomes, including neurologic deterioration in hospital (22.8% with CTP vs. 15.7% with DW-MRII, P = .286), symptomatic intracranial hemorrhage (4.1% with CTP vs. 4.8% with DW-MRI, P = 1.000), or death related to stroke (19.5% with CTP vs. 13.3% with DW-MRI, P = .263). Outcomes at 90 days proved to be similar between CTP and DW-MRI for achieving functional independence (29.3% vs. 34.9%, respectively; P = .445) and utility-weighted modified Rankin Scale scores (4.2 vs. 4.9, respectively; P = .172).

Multivariate analyses showed that 90-day functional independence was predicted by thrombectomy treatment, age, blood glucose level, baseline National Institutes of Health Stroke Scale score, and core lab ASPECTS (Alberta Stroke Program Early CT Score), but not the method of imaging.

“The efficacy and safety of mechanical thrombectomy for patients meeting those clinical mismatch criteria at 6-24 hours were comparable whether the small core infarcts were measured by diffusion imaging or cerebral blood flow imaging. I believe that future clinical trials aiming to extend the eligibility outside of this prespecified population should include both imaging modalities to determine whether these results are generalizable,” Dr. Sila said.

The DAWN study was funded by Stryker Neurovascular. Dr. Sila has reported receiving honoraria from Medtronic.

SOURCE: Sila C et al. ISC 2018, abstract LB11.

LOS ANGELES – The benefits of mechanical thrombectomy observed in the DAWN trial for patients with acute ischemic stroke and a mismatch between core imaging and clinical presentation out to 24 hours appear to apply regardless of whether their eligibility is determined by CT perfusion or diffusion-weighted magnetic resonance imaging, according to a subanalysis of the trial data.

Diffusion-weighted magnetic resonance imaging (DW-MRI) is considered the gold standard, but it is not as widely available as CT perfusion (CTP) and previous studies have shown that MR is associated with longer times between stroke onset and treatment randomization. “Though MR was originally preferred in DAWN, it was pretty clear that CT perfusion was going to need to be employed in the trial as well,” Cathy Sila, MD, said during her presentation of the results of the subanalysis at the International Stroke Conference 2018, sponsored by the American Heart Association.

The research sought to determine if the two imaging methods perform similarly. CTP is more readily available, but it has some issues. In patients with severe heart failure, a severe proximal stenosis, or a contralateral severe stenosis, the technique may struggle to accurately image the core infarct, which has led some to wonder if the outcomes would be as good using CTP as selection criteria. “In our institution, we’ve had this conversation very frequently,” said Dr. Sila, who is a vascular neurologist and the director of the University Hospitals Systems stroke program in Cleveland.

To be eligible for DAWN, the core infarct had to correspond to at least a 30% decrease in regional blood flow in the CTP map, or an apparent diffusion coefficient of less than 620 on DW-MRI.

The researchers included all 206 patients in the DAWN study (N Engl J Med. 2018;378:11-21), separating them into DW-MRI or CTP groups based on which imaging method was used to randomize them during the trial. There were no statistically significant differences in any of the baseline characteristics between the two imaging groups.

The 26 sites participating in DAWN had clear differences in their preferences for imaging techniques; 19 exclusively used CTP, 4 used only DW-MRI, and 3 sites used a combination of both imaging methods.

There were no statistically significant differences between the two groups in any of the measured clinical outcomes, including neurologic deterioration in hospital (22.8% with CTP vs. 15.7% with DW-MRII, P = .286), symptomatic intracranial hemorrhage (4.1% with CTP vs. 4.8% with DW-MRI, P = 1.000), or death related to stroke (19.5% with CTP vs. 13.3% with DW-MRI, P = .263). Outcomes at 90 days proved to be similar between CTP and DW-MRI for achieving functional independence (29.3% vs. 34.9%, respectively; P = .445) and utility-weighted modified Rankin Scale scores (4.2 vs. 4.9, respectively; P = .172).

Multivariate analyses showed that 90-day functional independence was predicted by thrombectomy treatment, age, blood glucose level, baseline National Institutes of Health Stroke Scale score, and core lab ASPECTS (Alberta Stroke Program Early CT Score), but not the method of imaging.

“The efficacy and safety of mechanical thrombectomy for patients meeting those clinical mismatch criteria at 6-24 hours were comparable whether the small core infarcts were measured by diffusion imaging or cerebral blood flow imaging. I believe that future clinical trials aiming to extend the eligibility outside of this prespecified population should include both imaging modalities to determine whether these results are generalizable,” Dr. Sila said.

The DAWN study was funded by Stryker Neurovascular. Dr. Sila has reported receiving honoraria from Medtronic.

SOURCE: Sila C et al. ISC 2018, abstract LB11.

Emicizumab looks like it’s headed toward approval in Europe for the prevention and reduction of bleeding episodes in patients with hemophilia A with factor VIII inhibitors.

The European Medicines Agency’s Committee for Medicinal Products for Human Use recommended granting marketing authorization to the drug in January 2018, according to a statement. The recommendation will now be considered by the European Commission.

Crystal/Wikimedia Commons/Creative Commons Attribution 2.0

Emicizumab, which is marketed in the United States as Hemlibra, was approved by the Food and Drug Administration for adult and pediatric patients with hemophilia A with Factor VIII inhibitors in November. It is the first monoclonal antibody to be recommended for use in patients with hemophilia A with inhibitors, says the statement.

[email protected]

Emicizumab looks like it’s headed toward approval in Europe for the prevention and reduction of bleeding episodes in patients with hemophilia A with factor VIII inhibitors.

The European Medicines Agency’s Committee for Medicinal Products for Human Use recommended granting marketing authorization to the drug in January 2018, according to a statement. The recommendation will now be considered by the European Commission.

Crystal/Wikimedia Commons/Creative Commons Attribution 2.0

Emicizumab, which is marketed in the United States as Hemlibra, was approved by the Food and Drug Administration for adult and pediatric patients with hemophilia A with Factor VIII inhibitors in November. It is the first monoclonal antibody to be recommended for use in patients with hemophilia A with inhibitors, says the statement.

[email protected]

Emicizumab looks like it’s headed toward approval in Europe for the prevention and reduction of bleeding episodes in patients with hemophilia A with factor VIII inhibitors.

The European Medicines Agency’s Committee for Medicinal Products for Human Use recommended granting marketing authorization to the drug in January 2018, according to a statement. The recommendation will now be considered by the European Commission.

Crystal/Wikimedia Commons/Creative Commons Attribution 2.0

Emicizumab, which is marketed in the United States as Hemlibra, was approved by the Food and Drug Administration for adult and pediatric patients with hemophilia A with Factor VIII inhibitors in November. It is the first monoclonal antibody to be recommended for use in patients with hemophilia A with inhibitors, says the statement.

[email protected]

Body mass index accounts for a 43.7% discordance in fibrosis findings between magnetic resonance elastography (MRE) and transient elastography (TE), according to a study from the University of California, San Diego.

“This study demonstrates that BMI is a significant factor of discordancy between MRE and TE for the stage of significant fibrosis (2-4 vs. 0-1),” wrote Cyrielle Caussy, MD, and her colleagues (Clin Gastrolenterol Hepatol. 2018 Jan 15. doi: 10.1016/j.cgh.2017.10.037). “Furthermore, this study showed that the grade of obesity is also a significant predictor of discordancy between MRE and TE because the discordance rate between MRE and TE increases with the increase in BMI.”

Dr. Caussy of the University of California, San Diego, and her colleagues had noted that MRE and TE had discordant findings in obese patients. To ascertain under what conditions TE and MRE produce the same readings, Dr. Caussy and her associates conducted a cross-sectional study of two cohorts with nonalcoholic fatty liver disease (NAFLD) who underwent contemporaneous MRE, TE, and liver biopsy. TE utilized both M and XL probes during imaging. The training cohort involved 119 adult patients undergoing NAFLD testing from October 2011 through January 2017. The validation cohort, consisting of 75 adults with NAFLD undergoing liver imaging from March 2010 through May 2013, was formed to validate the findings of the training cohort.

The study revealed that BMI was a significant predictor of the difference between MRE and TE results and made it difficult to assess the stage of liver fibrosis (2-4 vs. 0-1). After adjustment for age and sex, BMI accounted for a 5-unit increase of 1.694 (95% confidence interval, 1.145-2.507; P = .008). This was not a static relationship, and as BMI increased, so did the discordance between MRE and TE (P = .0309). Interestingly, the discordance rate was significantly higher in participants with BMIs greater than 35 kg/m², compared with participants with BMIs below 35 (63.0% vs. 38.0%; P = .022), the investigators reported. In severely obese adults with liver disease caused mainly by NAFLD, the accuracy of MRE was higher than TE for diagnosing significant fibrosis and advanced fibrosis.

While the study revealed valuable information, it had both strengths and limitations. A strength of the study was the use of two cohorts, specifically the validation cohort. The use of the liver biopsy as a reference, which is the standard for assessing fibrosis, was also a strength of the study. A limitation was that the study was conducted at specialized, tertiary care centers using advanced imaging techniques that may not be available at other clinics. Additionally, the cohorts included a small number of patients with advanced fibrosis.

“The integration of the BMI in the screening strategy for the noninvasive detection of liver fibrosis in NAFLD should be considered, and this parameter would help to determine when MRE is not needed in future guidelines” wrote Dr. Caussy and her associates. “Further cost-effectiveness studies are necessary to evaluate the clinical utility of MRE, TE, and/or liver biopsy to develop optimal screening strategies for diagnosing NAFLD-associated fibrosis.”

Jun Chen, MD, Meng Yin, MD, and Richard L. Ehman, MD, all have intellectual property rights and financial interests in elastography technology. Dr. Ehman also serves as an noncompensated CEO of Resoundant. Claude B. Sirlin, MD, has served as a consultant to Bayer and GE Healthcare. All other authors did not disclose any conflicts.

[email protected]

SOURCE: Caussy C et al. Clin Gastrolenterol Hepatol. 2018 Jan 15. doi: 10.1016/j.cgh.2017.10.037.

Body mass index accounts for a 43.7% discordance in fibrosis findings between magnetic resonance elastography (MRE) and transient elastography (TE), according to a study from the University of California, San Diego.

“This study demonstrates that BMI is a significant factor of discordancy between MRE and TE for the stage of significant fibrosis (2-4 vs. 0-1),” wrote Cyrielle Caussy, MD, and her colleagues (Clin Gastrolenterol Hepatol. 2018 Jan 15. doi: 10.1016/j.cgh.2017.10.037). “Furthermore, this study showed that the grade of obesity is also a significant predictor of discordancy between MRE and TE because the discordance rate between MRE and TE increases with the increase in BMI.”

Dr. Caussy of the University of California, San Diego, and her colleagues had noted that MRE and TE had discordant findings in obese patients. To ascertain under what conditions TE and MRE produce the same readings, Dr. Caussy and her associates conducted a cross-sectional study of two cohorts with nonalcoholic fatty liver disease (NAFLD) who underwent contemporaneous MRE, TE, and liver biopsy. TE utilized both M and XL probes during imaging. The training cohort involved 119 adult patients undergoing NAFLD testing from October 2011 through January 2017. The validation cohort, consisting of 75 adults with NAFLD undergoing liver imaging from March 2010 through May 2013, was formed to validate the findings of the training cohort.

The study revealed that BMI was a significant predictor of the difference between MRE and TE results and made it difficult to assess the stage of liver fibrosis (2-4 vs. 0-1). After adjustment for age and sex, BMI accounted for a 5-unit increase of 1.694 (95% confidence interval, 1.145-2.507; P = .008). This was not a static relationship, and as BMI increased, so did the discordance between MRE and TE (P = .0309). Interestingly, the discordance rate was significantly higher in participants with BMIs greater than 35 kg/m², compared with participants with BMIs below 35 (63.0% vs. 38.0%; P = .022), the investigators reported. In severely obese adults with liver disease caused mainly by NAFLD, the accuracy of MRE was higher than TE for diagnosing significant fibrosis and advanced fibrosis.

While the study revealed valuable information, it had both strengths and limitations. A strength of the study was the use of two cohorts, specifically the validation cohort. The use of the liver biopsy as a reference, which is the standard for assessing fibrosis, was also a strength of the study. A limitation was that the study was conducted at specialized, tertiary care centers using advanced imaging techniques that may not be available at other clinics. Additionally, the cohorts included a small number of patients with advanced fibrosis.

“The integration of the BMI in the screening strategy for the noninvasive detection of liver fibrosis in NAFLD should be considered, and this parameter would help to determine when MRE is not needed in future guidelines” wrote Dr. Caussy and her associates. “Further cost-effectiveness studies are necessary to evaluate the clinical utility of MRE, TE, and/or liver biopsy to develop optimal screening strategies for diagnosing NAFLD-associated fibrosis.”

Jun Chen, MD, Meng Yin, MD, and Richard L. Ehman, MD, all have intellectual property rights and financial interests in elastography technology. Dr. Ehman also serves as an noncompensated CEO of Resoundant. Claude B. Sirlin, MD, has served as a consultant to Bayer and GE Healthcare. All other authors did not disclose any conflicts.

[email protected]

SOURCE: Caussy C et al. Clin Gastrolenterol Hepatol. 2018 Jan 15. doi: 10.1016/j.cgh.2017.10.037.

Body mass index accounts for a 43.7% discordance in fibrosis findings between magnetic resonance elastography (MRE) and transient elastography (TE), according to a study from the University of California, San Diego.

“This study demonstrates that BMI is a significant factor of discordancy between MRE and TE for the stage of significant fibrosis (2-4 vs. 0-1),” wrote Cyrielle Caussy, MD, and her colleagues (Clin Gastrolenterol Hepatol. 2018 Jan 15. doi: 10.1016/j.cgh.2017.10.037). “Furthermore, this study showed that the grade of obesity is also a significant predictor of discordancy between MRE and TE because the discordance rate between MRE and TE increases with the increase in BMI.”

Dr. Caussy of the University of California, San Diego, and her colleagues had noted that MRE and TE had discordant findings in obese patients. To ascertain under what conditions TE and MRE produce the same readings, Dr. Caussy and her associates conducted a cross-sectional study of two cohorts with nonalcoholic fatty liver disease (NAFLD) who underwent contemporaneous MRE, TE, and liver biopsy. TE utilized both M and XL probes during imaging. The training cohort involved 119 adult patients undergoing NAFLD testing from October 2011 through January 2017. The validation cohort, consisting of 75 adults with NAFLD undergoing liver imaging from March 2010 through May 2013, was formed to validate the findings of the training cohort.

The study revealed that BMI was a significant predictor of the difference between MRE and TE results and made it difficult to assess the stage of liver fibrosis (2-4 vs. 0-1). After adjustment for age and sex, BMI accounted for a 5-unit increase of 1.694 (95% confidence interval, 1.145-2.507; P = .008). This was not a static relationship, and as BMI increased, so did the discordance between MRE and TE (P = .0309). Interestingly, the discordance rate was significantly higher in participants with BMIs greater than 35 kg/m², compared with participants with BMIs below 35 (63.0% vs. 38.0%; P = .022), the investigators reported. In severely obese adults with liver disease caused mainly by NAFLD, the accuracy of MRE was higher than TE for diagnosing significant fibrosis and advanced fibrosis.

While the study revealed valuable information, it had both strengths and limitations. A strength of the study was the use of two cohorts, specifically the validation cohort. The use of the liver biopsy as a reference, which is the standard for assessing fibrosis, was also a strength of the study. A limitation was that the study was conducted at specialized, tertiary care centers using advanced imaging techniques that may not be available at other clinics. Additionally, the cohorts included a small number of patients with advanced fibrosis.

“The integration of the BMI in the screening strategy for the noninvasive detection of liver fibrosis in NAFLD should be considered, and this parameter would help to determine when MRE is not needed in future guidelines” wrote Dr. Caussy and her associates. “Further cost-effectiveness studies are necessary to evaluate the clinical utility of MRE, TE, and/or liver biopsy to develop optimal screening strategies for diagnosing NAFLD-associated fibrosis.”

Jun Chen, MD, Meng Yin, MD, and Richard L. Ehman, MD, all have intellectual property rights and financial interests in elastography technology. Dr. Ehman also serves as an noncompensated CEO of Resoundant. Claude B. Sirlin, MD, has served as a consultant to Bayer and GE Healthcare. All other authors did not disclose any conflicts.

[email protected]

SOURCE: Caussy C et al. Clin Gastrolenterol Hepatol. 2018 Jan 15. doi: 10.1016/j.cgh.2017.10.037.

Neurologists should recommend twice-weekly exercise to patients diagnosed with mild cognitive impairment (MCI) as part of an overall approach to management, according to a practice guideline update from the American Academy of Neurology (AAN). The Level B recommendation is based on six-month studies that suggest that such exercise possibly improves cognition. The update was published online ahead of print December 27, 2017, in Neurology.

“Regular physical exercise has long been shown to have heart health benefits, and now we can say exercise also may help improve memory for people with MCI,” said Ronald Petersen, MD, PhD, Director of the Alzheimer’s Disease Research Center at the Mayo Clinic in Rochester, Minnesota, and lead author of the update. “What is good for your heart can be good for your brain.”

Document Updates 2001 Practice Parameter

The current practice guideline update revises the AAN’s 2001 practice parameter that provided recommendations for the diagnosis and treatment of MCI. Dr. Petersen and colleagues based the update on a systematic review of articles about MCI prevalence, prognosis, and treatment. They classified evidence according to AAN criteria and based recommendations on modified Delphi consensus.

The authors found that the prevalence of MCI is 6.7% for people between ages 60 and 64, 8.4% for people between ages 65 and 69, 10.1% for people between ages 70 and 74, 14.8% for people between ages 75 and 79, and 25.2% for people between ages 80 and 84. Approximately 15% of people with MCI who are older than 65 develop dementia during two years of follow-up.

No Evidence for Pharmacologic Treatment

Evidence does not support a symptomatic cognitive benefit in MCI for any pharmacologic or dietary agents, according to the authors. The FDA has not approved any medication for treating MCI. If clinicians offer cholinesterase inhibitors to their patients with MCI, they must first discuss the fact that the treatment is off label and not backed by empirical evidence, according to the update. Gastrointestinal symptoms and cardiac concerns are common side effects of cholinesterase inhibitors.

Assessment for MCI is appropriate for patients who complain of impaired memory or cognition, as well as those who present for a Medicare Annual Wellness Visit, according to the update. Clinicians should evaluate patients with MCI for risk factors that are potentially modifiable. Patients with MCI also should undergo serial assessments over time so that clinicians can monitor them for changes in cognitive status.

—Erik Greb

Suggested Reading

Langa KM, Levine DA. The diagnosis and management of mild cognitive impairment: a clinical review. JAMA. 2014;312(23):2551-2561.

Petersen RC, Lopez O, Armstrong MJ, et al. Practice guideline update summary: Mild cognitive impairment: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2017 Dec 27 [Epub ahead of print].

Vega JN, Newhouse PA. Mild cognitive impairment: diagnosis, longitudinal course, and emerging treatments. Curr Psychiatry Rep. 2014;16(10):490.

Neurologists should recommend twice-weekly exercise to patients diagnosed with mild cognitive impairment (MCI) as part of an overall approach to management, according to a practice guideline update from the American Academy of Neurology (AAN). The Level B recommendation is based on six-month studies that suggest that such exercise possibly improves cognition. The update was published online ahead of print December 27, 2017, in Neurology.

“Regular physical exercise has long been shown to have heart health benefits, and now we can say exercise also may help improve memory for people with MCI,” said Ronald Petersen, MD, PhD, Director of the Alzheimer’s Disease Research Center at the Mayo Clinic in Rochester, Minnesota, and lead author of the update. “What is good for your heart can be good for your brain.”

Document Updates 2001 Practice Parameter

The current practice guideline update revises the AAN’s 2001 practice parameter that provided recommendations for the diagnosis and treatment of MCI. Dr. Petersen and colleagues based the update on a systematic review of articles about MCI prevalence, prognosis, and treatment. They classified evidence according to AAN criteria and based recommendations on modified Delphi consensus.

The authors found that the prevalence of MCI is 6.7% for people between ages 60 and 64, 8.4% for people between ages 65 and 69, 10.1% for people between ages 70 and 74, 14.8% for people between ages 75 and 79, and 25.2% for people between ages 80 and 84. Approximately 15% of people with MCI who are older than 65 develop dementia during two years of follow-up.

No Evidence for Pharmacologic Treatment

Evidence does not support a symptomatic cognitive benefit in MCI for any pharmacologic or dietary agents, according to the authors. The FDA has not approved any medication for treating MCI. If clinicians offer cholinesterase inhibitors to their patients with MCI, they must first discuss the fact that the treatment is off label and not backed by empirical evidence, according to the update. Gastrointestinal symptoms and cardiac concerns are common side effects of cholinesterase inhibitors.

Assessment for MCI is appropriate for patients who complain of impaired memory or cognition, as well as those who present for a Medicare Annual Wellness Visit, according to the update. Clinicians should evaluate patients with MCI for risk factors that are potentially modifiable. Patients with MCI also should undergo serial assessments over time so that clinicians can monitor them for changes in cognitive status.

—Erik Greb

Suggested Reading

Langa KM, Levine DA. The diagnosis and management of mild cognitive impairment: a clinical review. JAMA. 2014;312(23):2551-2561.

Petersen RC, Lopez O, Armstrong MJ, et al. Practice guideline update summary: Mild cognitive impairment: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2017 Dec 27 [Epub ahead of print].

Vega JN, Newhouse PA. Mild cognitive impairment: diagnosis, longitudinal course, and emerging treatments. Curr Psychiatry Rep. 2014;16(10):490.

Neurologists should recommend twice-weekly exercise to patients diagnosed with mild cognitive impairment (MCI) as part of an overall approach to management, according to a practice guideline update from the American Academy of Neurology (AAN). The Level B recommendation is based on six-month studies that suggest that such exercise possibly improves cognition. The update was published online ahead of print December 27, 2017, in Neurology.

“Regular physical exercise has long been shown to have heart health benefits, and now we can say exercise also may help improve memory for people with MCI,” said Ronald Petersen, MD, PhD, Director of the Alzheimer’s Disease Research Center at the Mayo Clinic in Rochester, Minnesota, and lead author of the update. “What is good for your heart can be good for your brain.”

Document Updates 2001 Practice Parameter

The current practice guideline update revises the AAN’s 2001 practice parameter that provided recommendations for the diagnosis and treatment of MCI. Dr. Petersen and colleagues based the update on a systematic review of articles about MCI prevalence, prognosis, and treatment. They classified evidence according to AAN criteria and based recommendations on modified Delphi consensus.

The authors found that the prevalence of MCI is 6.7% for people between ages 60 and 64, 8.4% for people between ages 65 and 69, 10.1% for people between ages 70 and 74, 14.8% for people between ages 75 and 79, and 25.2% for people between ages 80 and 84. Approximately 15% of people with MCI who are older than 65 develop dementia during two years of follow-up.

No Evidence for Pharmacologic Treatment

Evidence does not support a symptomatic cognitive benefit in MCI for any pharmacologic or dietary agents, according to the authors. The FDA has not approved any medication for treating MCI. If clinicians offer cholinesterase inhibitors to their patients with MCI, they must first discuss the fact that the treatment is off label and not backed by empirical evidence, according to the update. Gastrointestinal symptoms and cardiac concerns are common side effects of cholinesterase inhibitors.

Assessment for MCI is appropriate for patients who complain of impaired memory or cognition, as well as those who present for a Medicare Annual Wellness Visit, according to the update. Clinicians should evaluate patients with MCI for risk factors that are potentially modifiable. Patients with MCI also should undergo serial assessments over time so that clinicians can monitor them for changes in cognitive status.

—Erik Greb

Suggested Reading

Langa KM, Levine DA. The diagnosis and management of mild cognitive impairment: a clinical review. JAMA. 2014;312(23):2551-2561.

Petersen RC, Lopez O, Armstrong MJ, et al. Practice guideline update summary: Mild cognitive impairment: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2017 Dec 27 [Epub ahead of print].

Vega JN, Newhouse PA. Mild cognitive impairment: diagnosis, longitudinal course, and emerging treatments. Curr Psychiatry Rep. 2014;16(10):490.

SNOWMASS, COLO. – By 2020, 75% of all isolated aortic valve replacements will be done as endovascular procedures, Michael J. Mack, MD, predicted at the Annual Cardiovascular Conference at Snowmass.

That’s assuming, hypothetically, that two ongoing randomized trials – PARTNER 3 and EVOLUT R – comparing TAVR (transcatheter aortic valve replacement) and SAVR (surgical aortic valve replacement) in low-surgical-risk patients have positive results. If so, TAVR will be proven noninferior to SAVR, as has already been convincingly shown in randomized trials conducted in high- and intermediate-surgical-risk patients.

Bruce Jancin/Frontline Medical News

• Younger patients. Many younger, low-surgical-risk patients will be concerned about TAVR valves’ durability and the current higher pacemaker rate.

“We have some idea of what durability is in the surgical population. What we usually quote is 12-15 years. There has been no major signal of early valve deterioration in TAVR, but there aren’t yet a significant number of patients alive for more than 5 years. Be that as it may, no significant concerns yet, but the other shoe hasn’t dropped,” the cardiothoracic surgeon observed.

Both PARTNER 3 and the EVOLUT R low-risk trial will follow participants annually for 10 years, eventually providing a robust, combined 2,000-patient database to assess comparative device durability.

The 30-day rates of permanent pacemaker implantation in TAVR recipients without a preexisting pacemaker is in the 12%-16% range with the newer-generation Evolut R and Sapien 3 valves. The indication is often new-onset left bundle branch block or complete heart block.

“I don’t think the increased pacemaker incidence is a huge problem now, but with the younger population I think it’s going to be more of an issue,” according to Dr. Mack. “It’s one thing to need a pacemaker if you’re 80-85 years old, but it’s totally different in somebody who’s 55 or 65 that has 30-35 years to live. Pacemaker leads are not benign in that population.”

“On the other hand, there is a thought that younger patients have less intrinsic conduction system disease. It may be that they are less prone to needing a new pacemaker afterward,” he added.

TAVR valve leaflet thrombosis is a concern. While a change in transvalvular gradient on echocardiography provides a signal for this complication, the actual diagnosis of valve thrombosis requires four-dimensional CT. Much better data on the true incidence and clinical ramifications of valve thrombosis in both TAVR and SAVR are coming. For example, the PARTNER 3 and EVOLUT R LR trials will each include 400-patient substudies with four-dimensional CT aimed at answering questions about valve thrombosis. The GALILEO trial, involving 1,520 TAVR patients, is designed to determine whether low-dose rivaroxaban prevents valve thrombosis and periprocedural embolization. Results of this randomized trial are due in about a year. Similarly, the 1,509-patient randomized ATLANTIS trial is looking at the effects of apixaban versus warfarin versus dual or single antiplatelet therapy.

If long-term anticoagulation in TAVR patients is found to be beneficial, that may steer some patients toward SAVR, especially if they are physically active or at high bleeding risk.

• Aortic stenosis patients with a high Syntax score and multivessel coronary artery disease. This group is best served by concomitant SAVR and coronary artery bypass grafting surgery.
• Patients with low or intermediate surgical risk with multivalve disease. “We know that patients with moderate to severe mitral regurgitation and/or moderate to severe tricuspid regurgitation do not do well after TAVR,” the surgeon said.
• Rheumatic valve disease patients.
• Patients who present at a site that offers SAVR only. “There are about 1,150 cardiac surgery programs in the United States and about 560 TAVR programs. There is concern that patients who don’t come in to a center that offers TAVR will not be offered TAVR as an option. I think there’s probably some truth to that,” Dr. Mack said.
• Patients going to sites without a well-functioning collaborative heart team. “In institutions where surgeons and cardiologists don’t get along, turf is much more of an issue, and surgeons are going to hold on to those patients more closely,” he observed.
• Patient’s with certain preferences. “All other things being equal, the patient is always going to choose the less invasive option. However, we do see some patients – I think it’s about 1 out of 10 – who express a preference to stay with the tried and true surgery,” according to Dr. Mack.

He reported receiving research grants from Abbott Vascular, Edwards Lifesciences, and Medtronic.

[email protected]

SNOWMASS, COLO. – By 2020, 75% of all isolated aortic valve replacements will be done as endovascular procedures, Michael J. Mack, MD, predicted at the Annual Cardiovascular Conference at Snowmass.

That’s assuming, hypothetically, that two ongoing randomized trials – PARTNER 3 and EVOLUT R – comparing TAVR (transcatheter aortic valve replacement) and SAVR (surgical aortic valve replacement) in low-surgical-risk patients have positive results. If so, TAVR will be proven noninferior to SAVR, as has already been convincingly shown in randomized trials conducted in high- and intermediate-surgical-risk patients.

Bruce Jancin/Frontline Medical News

• Younger patients. Many younger, low-surgical-risk patients will be concerned about TAVR valves’ durability and the current higher pacemaker rate.

“We have some idea of what durability is in the surgical population. What we usually quote is 12-15 years. There has been no major signal of early valve deterioration in TAVR, but there aren’t yet a significant number of patients alive for more than 5 years. Be that as it may, no significant concerns yet, but the other shoe hasn’t dropped,” the cardiothoracic surgeon observed.

Both PARTNER 3 and the EVOLUT R low-risk trial will follow participants annually for 10 years, eventually providing a robust, combined 2,000-patient database to assess comparative device durability.

The 30-day rates of permanent pacemaker implantation in TAVR recipients without a preexisting pacemaker is in the 12%-16% range with the newer-generation Evolut R and Sapien 3 valves. The indication is often new-onset left bundle branch block or complete heart block.

“I don’t think the increased pacemaker incidence is a huge problem now, but with the younger population I think it’s going to be more of an issue,” according to Dr. Mack. “It’s one thing to need a pacemaker if you’re 80-85 years old, but it’s totally different in somebody who’s 55 or 65 that has 30-35 years to live. Pacemaker leads are not benign in that population.”

“On the other hand, there is a thought that younger patients have less intrinsic conduction system disease. It may be that they are less prone to needing a new pacemaker afterward,” he added.

TAVR valve leaflet thrombosis is a concern. While a change in transvalvular gradient on echocardiography provides a signal for this complication, the actual diagnosis of valve thrombosis requires four-dimensional CT. Much better data on the true incidence and clinical ramifications of valve thrombosis in both TAVR and SAVR are coming. For example, the PARTNER 3 and EVOLUT R LR trials will each include 400-patient substudies with four-dimensional CT aimed at answering questions about valve thrombosis. The GALILEO trial, involving 1,520 TAVR patients, is designed to determine whether low-dose rivaroxaban prevents valve thrombosis and periprocedural embolization. Results of this randomized trial are due in about a year. Similarly, the 1,509-patient randomized ATLANTIS trial is looking at the effects of apixaban versus warfarin versus dual or single antiplatelet therapy.

If long-term anticoagulation in TAVR patients is found to be beneficial, that may steer some patients toward SAVR, especially if they are physically active or at high bleeding risk.

• Aortic stenosis patients with a high Syntax score and multivessel coronary artery disease. This group is best served by concomitant SAVR and coronary artery bypass grafting surgery.
• Patients with low or intermediate surgical risk with multivalve disease. “We know that patients with moderate to severe mitral regurgitation and/or moderate to severe tricuspid regurgitation do not do well after TAVR,” the surgeon said.
• Rheumatic valve disease patients.
• Patients who present at a site that offers SAVR only. “There are about 1,150 cardiac surgery programs in the United States and about 560 TAVR programs. There is concern that patients who don’t come in to a center that offers TAVR will not be offered TAVR as an option. I think there’s probably some truth to that,” Dr. Mack said.
• Patients going to sites without a well-functioning collaborative heart team. “In institutions where surgeons and cardiologists don’t get along, turf is much more of an issue, and surgeons are going to hold on to those patients more closely,” he observed.
• Patient’s with certain preferences. “All other things being equal, the patient is always going to choose the less invasive option. However, we do see some patients – I think it’s about 1 out of 10 – who express a preference to stay with the tried and true surgery,” according to Dr. Mack.

He reported receiving research grants from Abbott Vascular, Edwards Lifesciences, and Medtronic.

[email protected]

SNOWMASS, COLO. – By 2020, 75% of all isolated aortic valve replacements will be done as endovascular procedures, Michael J. Mack, MD, predicted at the Annual Cardiovascular Conference at Snowmass.

That’s assuming, hypothetically, that two ongoing randomized trials – PARTNER 3 and EVOLUT R – comparing TAVR (transcatheter aortic valve replacement) and SAVR (surgical aortic valve replacement) in low-surgical-risk patients have positive results. If so, TAVR will be proven noninferior to SAVR, as has already been convincingly shown in randomized trials conducted in high- and intermediate-surgical-risk patients.

Bruce Jancin/Frontline Medical News

• Younger patients. Many younger, low-surgical-risk patients will be concerned about TAVR valves’ durability and the current higher pacemaker rate.

“We have some idea of what durability is in the surgical population. What we usually quote is 12-15 years. There has been no major signal of early valve deterioration in TAVR, but there aren’t yet a significant number of patients alive for more than 5 years. Be that as it may, no significant concerns yet, but the other shoe hasn’t dropped,” the cardiothoracic surgeon observed.

Both PARTNER 3 and the EVOLUT R low-risk trial will follow participants annually for 10 years, eventually providing a robust, combined 2,000-patient database to assess comparative device durability.

The 30-day rates of permanent pacemaker implantation in TAVR recipients without a preexisting pacemaker is in the 12%-16% range with the newer-generation Evolut R and Sapien 3 valves. The indication is often new-onset left bundle branch block or complete heart block.

“I don’t think the increased pacemaker incidence is a huge problem now, but with the younger population I think it’s going to be more of an issue,” according to Dr. Mack. “It’s one thing to need a pacemaker if you’re 80-85 years old, but it’s totally different in somebody who’s 55 or 65 that has 30-35 years to live. Pacemaker leads are not benign in that population.”

“On the other hand, there is a thought that younger patients have less intrinsic conduction system disease. It may be that they are less prone to needing a new pacemaker afterward,” he added.

TAVR valve leaflet thrombosis is a concern. While a change in transvalvular gradient on echocardiography provides a signal for this complication, the actual diagnosis of valve thrombosis requires four-dimensional CT. Much better data on the true incidence and clinical ramifications of valve thrombosis in both TAVR and SAVR are coming. For example, the PARTNER 3 and EVOLUT R LR trials will each include 400-patient substudies with four-dimensional CT aimed at answering questions about valve thrombosis. The GALILEO trial, involving 1,520 TAVR patients, is designed to determine whether low-dose rivaroxaban prevents valve thrombosis and periprocedural embolization. Results of this randomized trial are due in about a year. Similarly, the 1,509-patient randomized ATLANTIS trial is looking at the effects of apixaban versus warfarin versus dual or single antiplatelet therapy.

If long-term anticoagulation in TAVR patients is found to be beneficial, that may steer some patients toward SAVR, especially if they are physically active or at high bleeding risk.

• Aortic stenosis patients with a high Syntax score and multivessel coronary artery disease. This group is best served by concomitant SAVR and coronary artery bypass grafting surgery.
• Patients with low or intermediate surgical risk with multivalve disease. “We know that patients with moderate to severe mitral regurgitation and/or moderate to severe tricuspid regurgitation do not do well after TAVR,” the surgeon said.
• Rheumatic valve disease patients.
• Patients who present at a site that offers SAVR only. “There are about 1,150 cardiac surgery programs in the United States and about 560 TAVR programs. There is concern that patients who don’t come in to a center that offers TAVR will not be offered TAVR as an option. I think there’s probably some truth to that,” Dr. Mack said.
• Patients going to sites without a well-functioning collaborative heart team. “In institutions where surgeons and cardiologists don’t get along, turf is much more of an issue, and surgeons are going to hold on to those patients more closely,” he observed.
• Patient’s with certain preferences. “All other things being equal, the patient is always going to choose the less invasive option. However, we do see some patients – I think it’s about 1 out of 10 – who express a preference to stay with the tried and true surgery,” according to Dr. Mack.

He reported receiving research grants from Abbott Vascular, Edwards Lifesciences, and Medtronic.

[email protected]