Joint mice or loose/rice bodies are infrequently encountered within joints. Usually, they are either fibrin or cartilaginous. The fibrin type, typically results from bleeding within a joint from synovitis, rheumatoid arthritis (RA), or tuberculosis, and the cartilaginous/osteocartilaginous type develop from trauma or osteoarthritis.¹ A rare cause of osteocartilaginous joint mice is synovial chondromatosis(SC), which can produce multiple loose bodies that originate from the synovial membranes of joints, bursae, and tendon sheaths of large joints; the knee being the most common (50%-65 % of cases).^1,2

A case of a male who had multiple years of left knee pain and swelling without a documented traumatic cause is presented

Case Presentation

A 34-year-old male veteran was evaluated and treated in a VA orthopedic outpatient clinic by a physician assistant for anterior left knee pain and swelling of insidious onset that had persisted for 1.5 years. The patient reported experiencing no trauma. His primary care provider already was treating the patient with nonsteroidal anti-inflammatory medications (NSAIDs), icing, and bracing. He had full motion in his knee with extension/flexion 0° to 130°. Collateral and cruciate ligaments were stable. He had a positive McMurray test. The X-rays showed no pathology. Due to the positive meniscal tear signs, a magnetic resonance image (MRI) was ordered.

The patient was intermittently nonadherent with follow-up care. The MRI results were available at a subsequent appointment 3 months after the index evaluation, which revealed a large joint effusion with rice bodies, small erosion of the posterior tibialplateau, and synovial proliferation of the anterior knee joint. A steroid injection to his affected knee was given. Concerns for possible RA led to a workup. The laboratory results included rheumatoid factor (weakly positive), antinuclear-antibodies (negative), human immunodeficiency virus (positivewith western blot negative), C-reactive protein (< 0.02 mg/L), erythrocyte sedimentation rate (5 mm/h), white blood cell count (4.6 µL), hepatitis B surface antigen (reactive), hepatitis A antibody (IgG reactive), synovial fluid cultures, and Gram stain (negative).

The patient saw a rheumatologist 7 months after a RA referral was processed. The consulting rheumatologist was unconcerned by a weakly positive rheumatoid factor, which was later repeated and was negative. The rheumatologist excluded the possibility of RA, and the patient was diagnosed with oligoarthritis. The treatment rendered was to continue NSAIDs and to return to the orthopedic clinic for continued care.

The patient had irregular follow-up visits where he received multiple methylprednisolone acetate intra-articular injections. His motion regressed until extension/flexion had decreased to 5°/85°. At this point the patient was forwarded to an operative orthopedic surgeon for evaluation for surgical intervention. Recent anteroposterior and lateral left knee X-rays showed faint intra-articular calcification, joint effusion, with mild arthritic changes of the patellofemoral joint (Figures 1A and 1B).

At surgery, on placing the infralateral portal, clear straw-colored fluid exited the cannula followed by copious small white rice bodies, which were sent to pathology for evaluation.  The knee was surgically evaluated, and extensive rice bodies were encountered (Figure 3). These were extracted with a full radius shaver. The chondral surfaces were inspected. There were no arthritic changes, but the synovial lining of the joint was hypertrophied and reactive (Milgram phase 2). After all loose bodies were extracted, the patient’s incisions were closed with nylon suture, and he was placed in sterile dressings with a postoperative range of motion brace.

The patient presented for his routine postoperative visit 14 days after surgery. Pathology results showed synociocytes, and inflammatory cells were negative for malignancy. The patient was forwarded to a local hospital for further evaluation and treatment by an orthopedic oncologist due to a reported 5% chance of malignant transformation.^1-3

Discussion

Synovial chondromatosis or osteochondromatosis is a rare, benign, metaplastic, typically monoarticular disorder of the synovial lining of joints, bursae, and synovial sheaths, usually affecting large joints.^1-5 Although any joint can be involved, such as metacarpalphalangeal joints, temporomandibular joints, distal radio-ulnar joints, and the hips, the knee is the most common with an occurrence rate 50% to 65%.^3-5 Extra-articular proliferation can be seen in cases of osteochondromatosis.² It is characterized by the formation of intra-articular nodules of the synovium that can detach and become loose bodies, which can secondarily become calcified/ossified.^4,6 The differential diagnosis associated with SC should include synovial hemangioma, pigmented villonodular synovitis, synovial cyst, lipoma arborescence, and malignancies, such as synovial chondrosarcoma or synovial sarcoma.³

Men are affected twice as much as are women, usually in the fourth through sixth decades of life, and a mean age of 47.7 years.^1,3-5,7,8 The SC occurrence rate in adults is 1:100,000.² Patients typically present with insidious gradual mechanical symptoms, such as pain (> 85% of cases), swelling (42%-58%), and decreased motion (38%-55%) in the affected joint.^2,3,6 Often there is crepitus with motion, diffuse tenderness, effusion, and occasionally nodules can be palpated.^2,3 Histologically, the synovium exhibits condrocytic metaplasia of fibroblasts with influence from transforming growth factor-β and bone morphogenic proteins.^1,4

Synovial chondromatosis can mimic osteoarthritis or meniscal pathology.³ Because of a chance of malignant transformation, any patient with rapid late deterioration of clinical features should be evaluated for chondrosarcoma or synovial sarcoma.^1-4 Plain radiographs may help differentiate the cause showing calcific joint mice and peri-articular erosions. However, the intra-articular loose bodies are frequently radiolucent, and a MRI may be warranted to definitively differentiate the diagnosis.^2,7,8

Loose bodies tend to exhibit a low signal on T1-weighted images and a high signal on T2-weighted images, although there may a be low signal on all images where there is extensive calcification of the loose bodies.² Ultrasound also is a useful diagnostic tool that can show numerous echogenic bodies, effusion, and synovial hypertrophy.²

A classic article by Milgram discussed the phases of the proliferative changes associated with SC, where phase 1 shows active intrasynovial disease with no loose bodies.⁹ Phase 2 has transitional lesions with osteochondral nodules within the synovial membrane and free bodies within the joint cavity. Last, in phase 3, there are multiple osteochondral free bodies but quiescent intrasynovial disease. The patient in this case study exhibited intra-articular activity mimicking phase 2 with extensive intra-articular loose bodies and reactive synovial lining.^3,9

In the early phase of the disease, conservative management may be trialed with NSAIDs, bracing, and injections, but typically surgical intervention is warranted after free bodies are found present, because they limit motion and cause recalcitrant swelling.^2,8 There is a controversy whether arthroscopic removal of loose bodies or excision with synovectomy is the treatment of choice.⁶ Ogilvie-Harris and colleagues reviewed the results of both procedures and found that although removal of loose bodies alone may be sufficient, there is the potential for recurrence.^9,10 In order to reduce potential recurrence, removal of loose bodies with anterior and posterior synovectomy is the treatment of choice.⁹

If arthroscopic removal of loose bodies without synovectomy is performed, then the patient should be followed closely for recurrence, which Jesalpura and colleagues reported to occur for 11.5% of patients.^9,11 If there is a reappearance, then a synovectomy should be performed.¹⁰ A recommended treatment option for recalcitrant SC is radiation, but this carries the added risk of perpetuating malignant transformation.^1,7

Unfortunately, osteoarthritis can be a significant long-term postoperative adverse effect.^3,6-8 This typically is related to the amount of articular damage that is present at surgery. Many times, the arthritis becomes significant enough to require total joint arthroplasty.⁴ Close long-term follow-up is recommended, because although rare, there is a chance of malignant change.^1-4

Conclusion

Synovial chondromatosis is an uncommon cause of knee pain and swelling and should be included in the differential diagnosis when evaluating any adult aged 30 years to 50 years with knee pain of insidious onset. Appropriate workup, intervention, and treatment will allow final diagnosis and correlating care to be administered to the patient.

Joint mice or loose/rice bodies are infrequently encountered within joints. Usually, they are either fibrin or cartilaginous. The fibrin type, typically results from bleeding within a joint from synovitis, rheumatoid arthritis (RA), or tuberculosis, and the cartilaginous/osteocartilaginous type develop from trauma or osteoarthritis.¹ A rare cause of osteocartilaginous joint mice is synovial chondromatosis(SC), which can produce multiple loose bodies that originate from the synovial membranes of joints, bursae, and tendon sheaths of large joints; the knee being the most common (50%-65 % of cases).^1,2

A case of a male who had multiple years of left knee pain and swelling without a documented traumatic cause is presented

Case Presentation

A 34-year-old male veteran was evaluated and treated in a VA orthopedic outpatient clinic by a physician assistant for anterior left knee pain and swelling of insidious onset that had persisted for 1.5 years. The patient reported experiencing no trauma. His primary care provider already was treating the patient with nonsteroidal anti-inflammatory medications (NSAIDs), icing, and bracing. He had full motion in his knee with extension/flexion 0° to 130°. Collateral and cruciate ligaments were stable. He had a positive McMurray test. The X-rays showed no pathology. Due to the positive meniscal tear signs, a magnetic resonance image (MRI) was ordered.

The patient was intermittently nonadherent with follow-up care. The MRI results were available at a subsequent appointment 3 months after the index evaluation, which revealed a large joint effusion with rice bodies, small erosion of the posterior tibialplateau, and synovial proliferation of the anterior knee joint. A steroid injection to his affected knee was given. Concerns for possible RA led to a workup. The laboratory results included rheumatoid factor (weakly positive), antinuclear-antibodies (negative), human immunodeficiency virus (positivewith western blot negative), C-reactive protein (< 0.02 mg/L), erythrocyte sedimentation rate (5 mm/h), white blood cell count (4.6 µL), hepatitis B surface antigen (reactive), hepatitis A antibody (IgG reactive), synovial fluid cultures, and Gram stain (negative).

The patient saw a rheumatologist 7 months after a RA referral was processed. The consulting rheumatologist was unconcerned by a weakly positive rheumatoid factor, which was later repeated and was negative. The rheumatologist excluded the possibility of RA, and the patient was diagnosed with oligoarthritis. The treatment rendered was to continue NSAIDs and to return to the orthopedic clinic for continued care.

The patient had irregular follow-up visits where he received multiple methylprednisolone acetate intra-articular injections. His motion regressed until extension/flexion had decreased to 5°/85°. At this point the patient was forwarded to an operative orthopedic surgeon for evaluation for surgical intervention. Recent anteroposterior and lateral left knee X-rays showed faint intra-articular calcification, joint effusion, with mild arthritic changes of the patellofemoral joint (Figures 1A and 1B).

At surgery, on placing the infralateral portal, clear straw-colored fluid exited the cannula followed by copious small white rice bodies, which were sent to pathology for evaluation.  The knee was surgically evaluated, and extensive rice bodies were encountered (Figure 3). These were extracted with a full radius shaver. The chondral surfaces were inspected. There were no arthritic changes, but the synovial lining of the joint was hypertrophied and reactive (Milgram phase 2). After all loose bodies were extracted, the patient’s incisions were closed with nylon suture, and he was placed in sterile dressings with a postoperative range of motion brace.

The patient presented for his routine postoperative visit 14 days after surgery. Pathology results showed synociocytes, and inflammatory cells were negative for malignancy. The patient was forwarded to a local hospital for further evaluation and treatment by an orthopedic oncologist due to a reported 5% chance of malignant transformation.^1-3

Discussion

Synovial chondromatosis or osteochondromatosis is a rare, benign, metaplastic, typically monoarticular disorder of the synovial lining of joints, bursae, and synovial sheaths, usually affecting large joints.^1-5 Although any joint can be involved, such as metacarpalphalangeal joints, temporomandibular joints, distal radio-ulnar joints, and the hips, the knee is the most common with an occurrence rate 50% to 65%.^3-5 Extra-articular proliferation can be seen in cases of osteochondromatosis.² It is characterized by the formation of intra-articular nodules of the synovium that can detach and become loose bodies, which can secondarily become calcified/ossified.^4,6 The differential diagnosis associated with SC should include synovial hemangioma, pigmented villonodular synovitis, synovial cyst, lipoma arborescence, and malignancies, such as synovial chondrosarcoma or synovial sarcoma.³

Men are affected twice as much as are women, usually in the fourth through sixth decades of life, and a mean age of 47.7 years.^1,3-5,7,8 The SC occurrence rate in adults is 1:100,000.² Patients typically present with insidious gradual mechanical symptoms, such as pain (> 85% of cases), swelling (42%-58%), and decreased motion (38%-55%) in the affected joint.^2,3,6 Often there is crepitus with motion, diffuse tenderness, effusion, and occasionally nodules can be palpated.^2,3 Histologically, the synovium exhibits condrocytic metaplasia of fibroblasts with influence from transforming growth factor-β and bone morphogenic proteins.^1,4

Synovial chondromatosis can mimic osteoarthritis or meniscal pathology.³ Because of a chance of malignant transformation, any patient with rapid late deterioration of clinical features should be evaluated for chondrosarcoma or synovial sarcoma.^1-4 Plain radiographs may help differentiate the cause showing calcific joint mice and peri-articular erosions. However, the intra-articular loose bodies are frequently radiolucent, and a MRI may be warranted to definitively differentiate the diagnosis.^2,7,8

Loose bodies tend to exhibit a low signal on T1-weighted images and a high signal on T2-weighted images, although there may a be low signal on all images where there is extensive calcification of the loose bodies.² Ultrasound also is a useful diagnostic tool that can show numerous echogenic bodies, effusion, and synovial hypertrophy.²

A classic article by Milgram discussed the phases of the proliferative changes associated with SC, where phase 1 shows active intrasynovial disease with no loose bodies.⁹ Phase 2 has transitional lesions with osteochondral nodules within the synovial membrane and free bodies within the joint cavity. Last, in phase 3, there are multiple osteochondral free bodies but quiescent intrasynovial disease. The patient in this case study exhibited intra-articular activity mimicking phase 2 with extensive intra-articular loose bodies and reactive synovial lining.^3,9

In the early phase of the disease, conservative management may be trialed with NSAIDs, bracing, and injections, but typically surgical intervention is warranted after free bodies are found present, because they limit motion and cause recalcitrant swelling.^2,8 There is a controversy whether arthroscopic removal of loose bodies or excision with synovectomy is the treatment of choice.⁶ Ogilvie-Harris and colleagues reviewed the results of both procedures and found that although removal of loose bodies alone may be sufficient, there is the potential for recurrence.^9,10 In order to reduce potential recurrence, removal of loose bodies with anterior and posterior synovectomy is the treatment of choice.⁹

If arthroscopic removal of loose bodies without synovectomy is performed, then the patient should be followed closely for recurrence, which Jesalpura and colleagues reported to occur for 11.5% of patients.^9,11 If there is a reappearance, then a synovectomy should be performed.¹⁰ A recommended treatment option for recalcitrant SC is radiation, but this carries the added risk of perpetuating malignant transformation.^1,7

Unfortunately, osteoarthritis can be a significant long-term postoperative adverse effect.^3,6-8 This typically is related to the amount of articular damage that is present at surgery. Many times, the arthritis becomes significant enough to require total joint arthroplasty.⁴ Close long-term follow-up is recommended, because although rare, there is a chance of malignant change.^1-4

Conclusion

Synovial chondromatosis is an uncommon cause of knee pain and swelling and should be included in the differential diagnosis when evaluating any adult aged 30 years to 50 years with knee pain of insidious onset. Appropriate workup, intervention, and treatment will allow final diagnosis and correlating care to be administered to the patient.

Joint mice or loose/rice bodies are infrequently encountered within joints. Usually, they are either fibrin or cartilaginous. The fibrin type, typically results from bleeding within a joint from synovitis, rheumatoid arthritis (RA), or tuberculosis, and the cartilaginous/osteocartilaginous type develop from trauma or osteoarthritis.¹ A rare cause of osteocartilaginous joint mice is synovial chondromatosis(SC), which can produce multiple loose bodies that originate from the synovial membranes of joints, bursae, and tendon sheaths of large joints; the knee being the most common (50%-65 % of cases).^1,2

A case of a male who had multiple years of left knee pain and swelling without a documented traumatic cause is presented

Case Presentation

A 34-year-old male veteran was evaluated and treated in a VA orthopedic outpatient clinic by a physician assistant for anterior left knee pain and swelling of insidious onset that had persisted for 1.5 years. The patient reported experiencing no trauma. His primary care provider already was treating the patient with nonsteroidal anti-inflammatory medications (NSAIDs), icing, and bracing. He had full motion in his knee with extension/flexion 0° to 130°. Collateral and cruciate ligaments were stable. He had a positive McMurray test. The X-rays showed no pathology. Due to the positive meniscal tear signs, a magnetic resonance image (MRI) was ordered.

The patient was intermittently nonadherent with follow-up care. The MRI results were available at a subsequent appointment 3 months after the index evaluation, which revealed a large joint effusion with rice bodies, small erosion of the posterior tibialplateau, and synovial proliferation of the anterior knee joint. A steroid injection to his affected knee was given. Concerns for possible RA led to a workup. The laboratory results included rheumatoid factor (weakly positive), antinuclear-antibodies (negative), human immunodeficiency virus (positivewith western blot negative), C-reactive protein (< 0.02 mg/L), erythrocyte sedimentation rate (5 mm/h), white blood cell count (4.6 µL), hepatitis B surface antigen (reactive), hepatitis A antibody (IgG reactive), synovial fluid cultures, and Gram stain (negative).

The patient saw a rheumatologist 7 months after a RA referral was processed. The consulting rheumatologist was unconcerned by a weakly positive rheumatoid factor, which was later repeated and was negative. The rheumatologist excluded the possibility of RA, and the patient was diagnosed with oligoarthritis. The treatment rendered was to continue NSAIDs and to return to the orthopedic clinic for continued care.

The patient had irregular follow-up visits where he received multiple methylprednisolone acetate intra-articular injections. His motion regressed until extension/flexion had decreased to 5°/85°. At this point the patient was forwarded to an operative orthopedic surgeon for evaluation for surgical intervention. Recent anteroposterior and lateral left knee X-rays showed faint intra-articular calcification, joint effusion, with mild arthritic changes of the patellofemoral joint (Figures 1A and 1B).

At surgery, on placing the infralateral portal, clear straw-colored fluid exited the cannula followed by copious small white rice bodies, which were sent to pathology for evaluation.  The knee was surgically evaluated, and extensive rice bodies were encountered (Figure 3). These were extracted with a full radius shaver. The chondral surfaces were inspected. There were no arthritic changes, but the synovial lining of the joint was hypertrophied and reactive (Milgram phase 2). After all loose bodies were extracted, the patient’s incisions were closed with nylon suture, and he was placed in sterile dressings with a postoperative range of motion brace.

The patient presented for his routine postoperative visit 14 days after surgery. Pathology results showed synociocytes, and inflammatory cells were negative for malignancy. The patient was forwarded to a local hospital for further evaluation and treatment by an orthopedic oncologist due to a reported 5% chance of malignant transformation.^1-3

Discussion

Synovial chondromatosis or osteochondromatosis is a rare, benign, metaplastic, typically monoarticular disorder of the synovial lining of joints, bursae, and synovial sheaths, usually affecting large joints.^1-5 Although any joint can be involved, such as metacarpalphalangeal joints, temporomandibular joints, distal radio-ulnar joints, and the hips, the knee is the most common with an occurrence rate 50% to 65%.^3-5 Extra-articular proliferation can be seen in cases of osteochondromatosis.² It is characterized by the formation of intra-articular nodules of the synovium that can detach and become loose bodies, which can secondarily become calcified/ossified.^4,6 The differential diagnosis associated with SC should include synovial hemangioma, pigmented villonodular synovitis, synovial cyst, lipoma arborescence, and malignancies, such as synovial chondrosarcoma or synovial sarcoma.³

Men are affected twice as much as are women, usually in the fourth through sixth decades of life, and a mean age of 47.7 years.^1,3-5,7,8 The SC occurrence rate in adults is 1:100,000.² Patients typically present with insidious gradual mechanical symptoms, such as pain (> 85% of cases), swelling (42%-58%), and decreased motion (38%-55%) in the affected joint.^2,3,6 Often there is crepitus with motion, diffuse tenderness, effusion, and occasionally nodules can be palpated.^2,3 Histologically, the synovium exhibits condrocytic metaplasia of fibroblasts with influence from transforming growth factor-β and bone morphogenic proteins.^1,4

Synovial chondromatosis can mimic osteoarthritis or meniscal pathology.³ Because of a chance of malignant transformation, any patient with rapid late deterioration of clinical features should be evaluated for chondrosarcoma or synovial sarcoma.^1-4 Plain radiographs may help differentiate the cause showing calcific joint mice and peri-articular erosions. However, the intra-articular loose bodies are frequently radiolucent, and a MRI may be warranted to definitively differentiate the diagnosis.^2,7,8

Loose bodies tend to exhibit a low signal on T1-weighted images and a high signal on T2-weighted images, although there may a be low signal on all images where there is extensive calcification of the loose bodies.² Ultrasound also is a useful diagnostic tool that can show numerous echogenic bodies, effusion, and synovial hypertrophy.²

A classic article by Milgram discussed the phases of the proliferative changes associated with SC, where phase 1 shows active intrasynovial disease with no loose bodies.⁹ Phase 2 has transitional lesions with osteochondral nodules within the synovial membrane and free bodies within the joint cavity. Last, in phase 3, there are multiple osteochondral free bodies but quiescent intrasynovial disease. The patient in this case study exhibited intra-articular activity mimicking phase 2 with extensive intra-articular loose bodies and reactive synovial lining.^3,9

In the early phase of the disease, conservative management may be trialed with NSAIDs, bracing, and injections, but typically surgical intervention is warranted after free bodies are found present, because they limit motion and cause recalcitrant swelling.^2,8 There is a controversy whether arthroscopic removal of loose bodies or excision with synovectomy is the treatment of choice.⁶ Ogilvie-Harris and colleagues reviewed the results of both procedures and found that although removal of loose bodies alone may be sufficient, there is the potential for recurrence.^9,10 In order to reduce potential recurrence, removal of loose bodies with anterior and posterior synovectomy is the treatment of choice.⁹

If arthroscopic removal of loose bodies without synovectomy is performed, then the patient should be followed closely for recurrence, which Jesalpura and colleagues reported to occur for 11.5% of patients.^9,11 If there is a reappearance, then a synovectomy should be performed.¹⁰ A recommended treatment option for recalcitrant SC is radiation, but this carries the added risk of perpetuating malignant transformation.^1,7

Unfortunately, osteoarthritis can be a significant long-term postoperative adverse effect.^3,6-8 This typically is related to the amount of articular damage that is present at surgery. Many times, the arthritis becomes significant enough to require total joint arthroplasty.⁴ Close long-term follow-up is recommended, because although rare, there is a chance of malignant change.^1-4

Conclusion

Synovial chondromatosis is an uncommon cause of knee pain and swelling and should be included in the differential diagnosis when evaluating any adult aged 30 years to 50 years with knee pain of insidious onset. Appropriate workup, intervention, and treatment will allow final diagnosis and correlating care to be administered to the patient.

Image by Lance Liotta

New research suggests SHARP1 may be a therapeutic target in MLL-AF6 acute myeloid leukemia (AML).

Researchers found that SHARP1, a circadian clock transcription factor, is overexpressed in MLL-AF6 AML.

In mouse models, suppression of SHARP1 induced apoptosis in leukemic cells, while deletion of SHARP1 delayed AML development and weakened leukemia-initiating potential.

“We found that MLL-AF6 binds with SHARP1, leading to an increase in the level of SHARP1,” explained study author Dan Tenen, MD, of the Cancer Science Institute of Singapore.

“The increase of SHARP1 levels has the 2-fold effect of initiating leukemia development, as well as maintaining the growth of leukemic cells. [O]ur study also revealed that SHARP1 could act upon other target genes of MLL-AF6 to aggravate the progression of AML, but, by removing or reducing the level of SHARP1, the growth of leukemic cells could be stopped.”

Dr Tenen and his colleagues reported these findings in Nature Communications.

The researchers found that SHARP1 was overexpressed in MLL-AF6 AML, but its expression was decreased in most other subtypes of AML analyzed as well as in normal bone marrow CD34+ cells.

Experiments in AML cell lines revealed that SHARP1 expression is regulated by MLL-AF6/DOT1L. The researchers said MLL-AF6 and MEN1/LEDGF directly bind to the SHARP1 gene locus to positively regulate SHARP1 expression through DOT1L activity.

Dr Tenen and his colleagues performed knockdown experiments in mice and found that SHARP1 plays a “critical” role in maintaining clonogenic growth and preventing apoptosis in MLL-AF6 AML cells.

The team also assessed the effects of SHARP1 deletion in mouse models of MLL-AF6 AML.

SHARP1 knockout mice had superior survival compared to wild-type mice. In addition, the knockout mice exhibited signs of less aggressive disease—fewer AML cells, lower white blood cell counts, and higher red blood cell counts.

The researchers also found that SHARP1 deletion reduced MLL-AF6 leukemia-initiating ability but did not affect normal hematopoiesis.

Finally, the team discovered that SHARP1 cooperates with MLL-AF6 to regulate target genes in MLL-AF6 AML cells.

Image by Lance Liotta

New research suggests SHARP1 may be a therapeutic target in MLL-AF6 acute myeloid leukemia (AML).

Researchers found that SHARP1, a circadian clock transcription factor, is overexpressed in MLL-AF6 AML.

In mouse models, suppression of SHARP1 induced apoptosis in leukemic cells, while deletion of SHARP1 delayed AML development and weakened leukemia-initiating potential.

“We found that MLL-AF6 binds with SHARP1, leading to an increase in the level of SHARP1,” explained study author Dan Tenen, MD, of the Cancer Science Institute of Singapore.

“The increase of SHARP1 levels has the 2-fold effect of initiating leukemia development, as well as maintaining the growth of leukemic cells. [O]ur study also revealed that SHARP1 could act upon other target genes of MLL-AF6 to aggravate the progression of AML, but, by removing or reducing the level of SHARP1, the growth of leukemic cells could be stopped.”

Dr Tenen and his colleagues reported these findings in Nature Communications.

The researchers found that SHARP1 was overexpressed in MLL-AF6 AML, but its expression was decreased in most other subtypes of AML analyzed as well as in normal bone marrow CD34+ cells.

Experiments in AML cell lines revealed that SHARP1 expression is regulated by MLL-AF6/DOT1L. The researchers said MLL-AF6 and MEN1/LEDGF directly bind to the SHARP1 gene locus to positively regulate SHARP1 expression through DOT1L activity.

Dr Tenen and his colleagues performed knockdown experiments in mice and found that SHARP1 plays a “critical” role in maintaining clonogenic growth and preventing apoptosis in MLL-AF6 AML cells.

The team also assessed the effects of SHARP1 deletion in mouse models of MLL-AF6 AML.

SHARP1 knockout mice had superior survival compared to wild-type mice. In addition, the knockout mice exhibited signs of less aggressive disease—fewer AML cells, lower white blood cell counts, and higher red blood cell counts.

The researchers also found that SHARP1 deletion reduced MLL-AF6 leukemia-initiating ability but did not affect normal hematopoiesis.

Finally, the team discovered that SHARP1 cooperates with MLL-AF6 to regulate target genes in MLL-AF6 AML cells.

Image by Lance Liotta

New research suggests SHARP1 may be a therapeutic target in MLL-AF6 acute myeloid leukemia (AML).

Researchers found that SHARP1, a circadian clock transcription factor, is overexpressed in MLL-AF6 AML.

In mouse models, suppression of SHARP1 induced apoptosis in leukemic cells, while deletion of SHARP1 delayed AML development and weakened leukemia-initiating potential.

“We found that MLL-AF6 binds with SHARP1, leading to an increase in the level of SHARP1,” explained study author Dan Tenen, MD, of the Cancer Science Institute of Singapore.

“The increase of SHARP1 levels has the 2-fold effect of initiating leukemia development, as well as maintaining the growth of leukemic cells. [O]ur study also revealed that SHARP1 could act upon other target genes of MLL-AF6 to aggravate the progression of AML, but, by removing or reducing the level of SHARP1, the growth of leukemic cells could be stopped.”

Dr Tenen and his colleagues reported these findings in Nature Communications.

The researchers found that SHARP1 was overexpressed in MLL-AF6 AML, but its expression was decreased in most other subtypes of AML analyzed as well as in normal bone marrow CD34+ cells.

Experiments in AML cell lines revealed that SHARP1 expression is regulated by MLL-AF6/DOT1L. The researchers said MLL-AF6 and MEN1/LEDGF directly bind to the SHARP1 gene locus to positively regulate SHARP1 expression through DOT1L activity.

Dr Tenen and his colleagues performed knockdown experiments in mice and found that SHARP1 plays a “critical” role in maintaining clonogenic growth and preventing apoptosis in MLL-AF6 AML cells.

The team also assessed the effects of SHARP1 deletion in mouse models of MLL-AF6 AML.

SHARP1 knockout mice had superior survival compared to wild-type mice. In addition, the knockout mice exhibited signs of less aggressive disease—fewer AML cells, lower white blood cell counts, and higher red blood cell counts.

The researchers also found that SHARP1 deletion reduced MLL-AF6 leukemia-initiating ability but did not affect normal hematopoiesis.

Finally, the team discovered that SHARP1 cooperates with MLL-AF6 to regulate target genes in MLL-AF6 AML cells.

The US Food and Drug Administration (FDA) has placed a partial hold on clinical trials of tazemetostat, an EZH2 inhibitor being developed to treat solid tumors and lymphomas.

The hold has halted enrollment in US-based trials of tazemetostat, but study subjects who have not experienced disease progression may continue to receive the drug.

The hold is due to an adverse event observed in a pediatric patient on a phase 1 study of tazemetostat.

The patient, who had advanced poorly differentiated chordoma, developed a secondary T-cell lymphoma while taking tazemetostat.

The patient had been on study for approximately 15 months and had achieved a confirmed partial response. Now, the patient has discontinued tazemetostat and is being treated for T-cell lymphoma.

More than 750 patients have been treated with tazemetostat to date, and this is the only case of secondary lymphoma that has been observed, according to Epizyme, Inc., the company developing tazemetostat.

The company also noted that doses of tazemetostat explored in its phase 1 pediatric study are higher than those used in the phase 2 adult studies.

Epizyme has begun taking steps to address the hold on tazemetostat trials—updating the informed consent, investigator’s brochure, and study protocols.

The company will need to confirm alignment with the FDA in order to resume US enrollment.

“We are working expeditiously with clinical trial investigators and regulatory authorities to initiate the appropriate steps to resume enrollment,” said Robert Bazemore, president and chief executive officer of Epizyme.

“Epizyme, along with our global investigator community, has been very encouraged by the clinical responses and tolerability of tazemetostat observed in pediatric and adult patients with hematological malignancies and solid tumors enrolled in our trials. We remain encouraged by the potential of tazemetostat to address the unmet needs of many patients living with cancer.”

The US Food and Drug Administration (FDA) has placed a partial hold on clinical trials of tazemetostat, an EZH2 inhibitor being developed to treat solid tumors and lymphomas.

The hold has halted enrollment in US-based trials of tazemetostat, but study subjects who have not experienced disease progression may continue to receive the drug.

The hold is due to an adverse event observed in a pediatric patient on a phase 1 study of tazemetostat.

The patient, who had advanced poorly differentiated chordoma, developed a secondary T-cell lymphoma while taking tazemetostat.

The patient had been on study for approximately 15 months and had achieved a confirmed partial response. Now, the patient has discontinued tazemetostat and is being treated for T-cell lymphoma.

More than 750 patients have been treated with tazemetostat to date, and this is the only case of secondary lymphoma that has been observed, according to Epizyme, Inc., the company developing tazemetostat.

The company also noted that doses of tazemetostat explored in its phase 1 pediatric study are higher than those used in the phase 2 adult studies.

Epizyme has begun taking steps to address the hold on tazemetostat trials—updating the informed consent, investigator’s brochure, and study protocols.

The company will need to confirm alignment with the FDA in order to resume US enrollment.

“We are working expeditiously with clinical trial investigators and regulatory authorities to initiate the appropriate steps to resume enrollment,” said Robert Bazemore, president and chief executive officer of Epizyme.

“Epizyme, along with our global investigator community, has been very encouraged by the clinical responses and tolerability of tazemetostat observed in pediatric and adult patients with hematological malignancies and solid tumors enrolled in our trials. We remain encouraged by the potential of tazemetostat to address the unmet needs of many patients living with cancer.”

The US Food and Drug Administration (FDA) has placed a partial hold on clinical trials of tazemetostat, an EZH2 inhibitor being developed to treat solid tumors and lymphomas.

The hold has halted enrollment in US-based trials of tazemetostat, but study subjects who have not experienced disease progression may continue to receive the drug.

The hold is due to an adverse event observed in a pediatric patient on a phase 1 study of tazemetostat.

The patient, who had advanced poorly differentiated chordoma, developed a secondary T-cell lymphoma while taking tazemetostat.

The patient had been on study for approximately 15 months and had achieved a confirmed partial response. Now, the patient has discontinued tazemetostat and is being treated for T-cell lymphoma.

More than 750 patients have been treated with tazemetostat to date, and this is the only case of secondary lymphoma that has been observed, according to Epizyme, Inc., the company developing tazemetostat.

The company also noted that doses of tazemetostat explored in its phase 1 pediatric study are higher than those used in the phase 2 adult studies.

Epizyme has begun taking steps to address the hold on tazemetostat trials—updating the informed consent, investigator’s brochure, and study protocols.

The company will need to confirm alignment with the FDA in order to resume US enrollment.

“We are working expeditiously with clinical trial investigators and regulatory authorities to initiate the appropriate steps to resume enrollment,” said Robert Bazemore, president and chief executive officer of Epizyme.

“Epizyme, along with our global investigator community, has been very encouraged by the clinical responses and tolerability of tazemetostat observed in pediatric and adult patients with hematological malignancies and solid tumors enrolled in our trials. We remain encouraged by the potential of tazemetostat to address the unmet needs of many patients living with cancer.”

Photo by Bill Branson

A new checklist could improve education for parents and other caregivers of children newly diagnosed with cancer, according to a group of nurses.

The checklist is divided into topics that should be taught according to their level of urgency.

The list includes subjects that should be discussed prior to patients’ initial hospital discharge and topics that can be covered later, either within the first month of the patients’ cancer diagnosis or before patients complete therapy.

Cheryl Rodgers, PhD, RN, and her colleagues provided details on this checklist in the Journal of Pediatric Oncology Nursing.

A team of 19 nurses and 2 parent advocates from the Children’s Oncology Group developed the checklist based on existing education checklists, expert recommendations, and team-based activities and discussions.

The checklist is divided into primary, secondary, and tertiary topics.

Primary topics are those that should be discussed with caregivers before they leave the hospital the first time. Examples include home medication dose and frequency, who and when to call for help, preventing infection, and treatment side effects to know before the next appointment.

Secondary topics are those that can be covered during the first month after a child’s cancer diagnosis. Examples include an explanation of what cancer is, an overview of chemotherapy, and more details on the side effects of cancer treatment.

Tertiary topics can be discussed before the child finishes cancer treatment. Examples include details on tests and procedures, risky behaviors to avoid, coping skills, and insurance issues.

Dr Rodgers and her colleagues said this checklist provides nurses with a clear outline of topics that should be discussed with caregivers immediately and topics that can be safely deferred. This could prevent information overload and help caregivers remember the most important information.

Photo by Bill Branson

A new checklist could improve education for parents and other caregivers of children newly diagnosed with cancer, according to a group of nurses.

The checklist is divided into topics that should be taught according to their level of urgency.

The list includes subjects that should be discussed prior to patients’ initial hospital discharge and topics that can be covered later, either within the first month of the patients’ cancer diagnosis or before patients complete therapy.

Cheryl Rodgers, PhD, RN, and her colleagues provided details on this checklist in the Journal of Pediatric Oncology Nursing.

A team of 19 nurses and 2 parent advocates from the Children’s Oncology Group developed the checklist based on existing education checklists, expert recommendations, and team-based activities and discussions.

The checklist is divided into primary, secondary, and tertiary topics.

Primary topics are those that should be discussed with caregivers before they leave the hospital the first time. Examples include home medication dose and frequency, who and when to call for help, preventing infection, and treatment side effects to know before the next appointment.

Secondary topics are those that can be covered during the first month after a child’s cancer diagnosis. Examples include an explanation of what cancer is, an overview of chemotherapy, and more details on the side effects of cancer treatment.

Tertiary topics can be discussed before the child finishes cancer treatment. Examples include details on tests and procedures, risky behaviors to avoid, coping skills, and insurance issues.

Dr Rodgers and her colleagues said this checklist provides nurses with a clear outline of topics that should be discussed with caregivers immediately and topics that can be safely deferred. This could prevent information overload and help caregivers remember the most important information.

Photo by Bill Branson

A new checklist could improve education for parents and other caregivers of children newly diagnosed with cancer, according to a group of nurses.

The checklist is divided into topics that should be taught according to their level of urgency.

The list includes subjects that should be discussed prior to patients’ initial hospital discharge and topics that can be covered later, either within the first month of the patients’ cancer diagnosis or before patients complete therapy.

Cheryl Rodgers, PhD, RN, and her colleagues provided details on this checklist in the Journal of Pediatric Oncology Nursing.

A team of 19 nurses and 2 parent advocates from the Children’s Oncology Group developed the checklist based on existing education checklists, expert recommendations, and team-based activities and discussions.

The checklist is divided into primary, secondary, and tertiary topics.

Primary topics are those that should be discussed with caregivers before they leave the hospital the first time. Examples include home medication dose and frequency, who and when to call for help, preventing infection, and treatment side effects to know before the next appointment.

Secondary topics are those that can be covered during the first month after a child’s cancer diagnosis. Examples include an explanation of what cancer is, an overview of chemotherapy, and more details on the side effects of cancer treatment.

Tertiary topics can be discussed before the child finishes cancer treatment. Examples include details on tests and procedures, risky behaviors to avoid, coping skills, and insurance issues.

Dr Rodgers and her colleagues said this checklist provides nurses with a clear outline of topics that should be discussed with caregivers immediately and topics that can be safely deferred. This could prevent information overload and help caregivers remember the most important information.

Micrograph showing ALL

The US Food and Drug Administration (FDA) has granted orphan drug designation to LBS-007 as a treatment for acute lymphoblastic leukemia (ALL).

LBS-007 is a non-ATP cell-cycle inhibitor targeting a range of cancers.

LBS-007 functions by blocking the kinase activity of CDC7, a key regulator of the cancer cell cycle.

Inhibiting CDC7 stops the proliferation of tumor cells and results in cell death.

Lin BioScience, Inc., the company developing LBS-007, said the drug has demonstrated “very potent activity” against leukemia and solid tumors in preclinical studies.

The company is expected to launch a phase 1 trial of LBS-007 in drug-resistant and refractory acute leukemia in the fourth quarter of 2018.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Micrograph showing ALL

The US Food and Drug Administration (FDA) has granted orphan drug designation to LBS-007 as a treatment for acute lymphoblastic leukemia (ALL).

LBS-007 is a non-ATP cell-cycle inhibitor targeting a range of cancers.

LBS-007 functions by blocking the kinase activity of CDC7, a key regulator of the cancer cell cycle.

Inhibiting CDC7 stops the proliferation of tumor cells and results in cell death.

Lin BioScience, Inc., the company developing LBS-007, said the drug has demonstrated “very potent activity” against leukemia and solid tumors in preclinical studies.

The company is expected to launch a phase 1 trial of LBS-007 in drug-resistant and refractory acute leukemia in the fourth quarter of 2018.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Micrograph showing ALL

The US Food and Drug Administration (FDA) has granted orphan drug designation to LBS-007 as a treatment for acute lymphoblastic leukemia (ALL).

LBS-007 is a non-ATP cell-cycle inhibitor targeting a range of cancers.

LBS-007 functions by blocking the kinase activity of CDC7, a key regulator of the cancer cell cycle.

Inhibiting CDC7 stops the proliferation of tumor cells and results in cell death.

Lin BioScience, Inc., the company developing LBS-007, said the drug has demonstrated “very potent activity” against leukemia and solid tumors in preclinical studies.

The company is expected to launch a phase 1 trial of LBS-007 in drug-resistant and refractory acute leukemia in the fourth quarter of 2018.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

KAUAI, HAWAII – The recent report that the risk of a major adverse cardiovascular event increases by 1% more than in the general population for each additional year of psoriasis duration is sobering news for physicians who treat pediatric psoriasis.

“If I have a 16-year-old who has a 5-year history of psoriasis, what does that mean for when she’s 30 or 40? And should we be intervening more aggressively?” Lawrence F. Eichenfield, MD, asked at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Bruce Jancin/MDedge News

Psoriasis develops during childhood in almost one-third of patients.

The pediatric psoriasis screening guidelines describe a simple routine screening program and timeline for early identification of overweight or obesity, type 2 diabetes, hypertension, nonalcoholic fatty liver disease, anxiety, depression, substance abuse, inflammatory bowel disease, and quality of life issues, all of which are encountered with increased frequency in pediatric psoriasis patients. A fasting lipid panel is recommended in children aged 9-11 years with psoriasis and again at age 17-21 years.

“Don’t forget arthritis. For a kid with psoriasis, at every office visit, I ask about morning stiffness or limp. Those are probably the two most sensitive questions in screening for psoriatic arthritis,” according to Dr. Eichenfield.

It has been clear for some time that the skin is not the only organ affected by psoriatic inflammation. The study that quantified the relationship between psoriasis duration and cardiovascular risk – a 1% increase for each year of psoriasis – was a collaboration between investigators at the University of Copenhagen and the University of Pennsylvania, Philadelphia.

The two-part project included aortal imaging of 190 psoriasis patients using fludeoxyglucose F 18 PET/CT scan, which showed a strong relationship between duration of psoriasis and the degree of vascular inflammation. This was bolstered by a population-based study using Danish national registry data on 87,161 psoriasis patients and 4.2 million controls from the general Danish population (J Am Acad Dermatol. 2017 Oct;77[4]:650-56.e3).

Dr. Eichenfield reported serving as a consultant to and/or recipient of research grants from more than a dozen pharmaceutical companies.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]
 

KAUAI, HAWAII – The recent report that the risk of a major adverse cardiovascular event increases by 1% more than in the general population for each additional year of psoriasis duration is sobering news for physicians who treat pediatric psoriasis.

“If I have a 16-year-old who has a 5-year history of psoriasis, what does that mean for when she’s 30 or 40? And should we be intervening more aggressively?” Lawrence F. Eichenfield, MD, asked at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Bruce Jancin/MDedge News

Psoriasis develops during childhood in almost one-third of patients.

The pediatric psoriasis screening guidelines describe a simple routine screening program and timeline for early identification of overweight or obesity, type 2 diabetes, hypertension, nonalcoholic fatty liver disease, anxiety, depression, substance abuse, inflammatory bowel disease, and quality of life issues, all of which are encountered with increased frequency in pediatric psoriasis patients. A fasting lipid panel is recommended in children aged 9-11 years with psoriasis and again at age 17-21 years.

“Don’t forget arthritis. For a kid with psoriasis, at every office visit, I ask about morning stiffness or limp. Those are probably the two most sensitive questions in screening for psoriatic arthritis,” according to Dr. Eichenfield.

It has been clear for some time that the skin is not the only organ affected by psoriatic inflammation. The study that quantified the relationship between psoriasis duration and cardiovascular risk – a 1% increase for each year of psoriasis – was a collaboration between investigators at the University of Copenhagen and the University of Pennsylvania, Philadelphia.

The two-part project included aortal imaging of 190 psoriasis patients using fludeoxyglucose F 18 PET/CT scan, which showed a strong relationship between duration of psoriasis and the degree of vascular inflammation. This was bolstered by a population-based study using Danish national registry data on 87,161 psoriasis patients and 4.2 million controls from the general Danish population (J Am Acad Dermatol. 2017 Oct;77[4]:650-56.e3).

Dr. Eichenfield reported serving as a consultant to and/or recipient of research grants from more than a dozen pharmaceutical companies.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]
 

KAUAI, HAWAII – The recent report that the risk of a major adverse cardiovascular event increases by 1% more than in the general population for each additional year of psoriasis duration is sobering news for physicians who treat pediatric psoriasis.

“If I have a 16-year-old who has a 5-year history of psoriasis, what does that mean for when she’s 30 or 40? And should we be intervening more aggressively?” Lawrence F. Eichenfield, MD, asked at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Bruce Jancin/MDedge News

Psoriasis develops during childhood in almost one-third of patients.

The pediatric psoriasis screening guidelines describe a simple routine screening program and timeline for early identification of overweight or obesity, type 2 diabetes, hypertension, nonalcoholic fatty liver disease, anxiety, depression, substance abuse, inflammatory bowel disease, and quality of life issues, all of which are encountered with increased frequency in pediatric psoriasis patients. A fasting lipid panel is recommended in children aged 9-11 years with psoriasis and again at age 17-21 years.

“Don’t forget arthritis. For a kid with psoriasis, at every office visit, I ask about morning stiffness or limp. Those are probably the two most sensitive questions in screening for psoriatic arthritis,” according to Dr. Eichenfield.

It has been clear for some time that the skin is not the only organ affected by psoriatic inflammation. The study that quantified the relationship between psoriasis duration and cardiovascular risk – a 1% increase for each year of psoriasis – was a collaboration between investigators at the University of Copenhagen and the University of Pennsylvania, Philadelphia.

The two-part project included aortal imaging of 190 psoriasis patients using fludeoxyglucose F 18 PET/CT scan, which showed a strong relationship between duration of psoriasis and the degree of vascular inflammation. This was bolstered by a population-based study using Danish national registry data on 87,161 psoriasis patients and 4.2 million controls from the general Danish population (J Am Acad Dermatol. 2017 Oct;77[4]:650-56.e3).

Dr. Eichenfield reported serving as a consultant to and/or recipient of research grants from more than a dozen pharmaceutical companies.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]
 

The Food and Drug Administration Arthritis Advisory Committee has voted to recommend the 2-mg dose of baricitinib, an orally administered Janus kinase (JAK) inhibitor, to treat adults with moderate to severe rheumatoid arthritis who have responded inadequately or poorly to methotrexate but rejected a 4-mg dose of the same drug.

In separate votes on efficacy of the 2-mg and 4-mg doses of baricitinib (14-1 and 15-0, respectively), on their safety (9-6 and 4-11), and on their benefit-risk ratio (10-5 and 5-10), the advisory committee consistently backed the 2-mg dose, but the committee rejected the 4-mg dose despite its effectiveness in improving the symptoms of rheumatoid arthritis. Although the FDA does not always follow the advice of its advisory committees, it generally does.

The New Drug Application was resubmitted by Eli Lilly and Incyte. The proposed doses included a 2-mg once-daily dose and a 4-mg dose for some patients. The original submission was filed in January of 2016 with an indication to treat moderate to severe rheumatoid arthritis, but that application was rejected primarily because of concerns about thrombotic events. Other issues with the original application included inadequate safety exposure for the 2-mg dose of baricitinib, as well as inconsistent findings concerning the efficacy of the higher 4-mg dose.

The resubmission addressed several of the issues noted by the FDA, and changed the indication to treat patients with moderate to severe RA who have had an inadequate response to methotrexate. Along with the different indication, the dosing regimen shifted to 2 mg once daily. For patients who did not adequately respond to disease-modifying antirheumatic drugs (DMARDS) or had an intolerance for one or more of these drugs, a 4-mg dose was recommended; after disease activity had been controlled, a taper to 2 mg once daily could be considered.

Apart from changes in the drug dosage and indication, the resubmission also included accumulated safety data, comparative epidemiologic data concerning venous thromboembolism and pulmonary embolism, and efficacy analyses to support the new dosing recommendations.

“The risk-benefit ratio may be less good here,” stated Donald Miller, PharmD, a professor of pharmacy practice at North Dakota State University, Fargo. “If there is a safety issue, it’s more likely to be a problem with the 4-mg dose.”

Jon Russell, MD, PhD, medical director of Fibromyalgia Research and Consulting, San Antonio, felt that the manufacturer understood that the safety signal indicated that the benefits outweighed the risks with the 4-mg dose of baricitinib.

“The drug is efficacious in resistant rheumatoid arthritis, and rheumatoid arthritis is a devastating disease. Organs are being destroyed, joints as well as organs, and it’s war. We need to make the patient aware that it’s war and then fight it like it is,” he said.

Many of the committee members mentioned that the efficacies of the 2-mg and 4-mg doses were not in question, primarily based on the data from four phase 3 clinical trials.

The studies RA-BEACON (JADW), RA-BUILD (JADX), RA-BEGIN (JADZ), and RA-BEAM (JADV) were all randomized phase 3 trials that evaluated the efficacy of baricitinib in patients with moderate to severe RA.

RA-BEACON and RA-BUILD both had similar designs and compared 2-mg and 4-mg doses of baricitinib with placebo; the trials primarily differed in their patient populations.

RA-BEACON. Investigators looked at 527 randomized patients who had failed treatment with a biologic DMARD with nearly half failing multiple classes of this drug. The primary endpoint for this study was met, with the 4-mg dose showing superior results, compared with placebo, based on American College of Rheumatology (ACR) 20 scores (P less than .0001). As early as week 1 of the trial, both patients receiving 2 mg and those receiving 4 mg of baricitinib showed significant improvement, compared with placebo. By week 4, the 4-mg dose produced as much improvement as the 2-mg dose achieved over nearly 6 months. While the 4-mg dose was considered more effective, the 2-mg dose showed improvement in ACR 20 scores, change in Disease Activity Score 28 C-reactive protein (DAS28-CRP), and change in health assessment questionnaire disability index (HAQ-DI) (P less than .001). Neither the 4-mg nor the 2-mg dose was able to reduce Simple Disease Activity Index (SDAI) scores, a difficult endpoint to achieve, particularly in such a short time frame.

RA-BUILD. The researchers looked at patients who had failed treatment with conventional DMARDs and had not been treated with biologic DMARDS. The investigators looked at 684 randomized patients and saw similar results to RA-BEACON, with both the 2-mg and 4-mg doses displaying significant improvement in ACR 20, change in DAS28-CRP, and change in HAQ-DI, as well as SDAI remission which had been absent in RA-BEACON. Patients taking the 4-mg dose showed improvement in morning joint stiffness duration and severity (P less than .0001), as well as improvements in worst joint pain (P less than .0001) and tiredness (P less than .027).

RA-BEGIN. The investigators took a different approach and compared various drug combinations, including baricitinib 4 mg alone or in combination with oral methotrexate or in patients taking methotrexate who were DMARD-naive. Ultimately, this trial displayed that baricitinib 4 mg alone was superior to methotrexate, according to ACR 20 scores. This held true across all clinical measures at week 24 whether baricitinib was administered alone or in combination with methotrexate. As it had in the previously discussed trials, the 4-mg dose improved all of the previously mentioned test scores, compared with methotrexate (P less than .0001) except for modified Total Sharp Score (mTSS) (P = 0.158). When baricitinib 4 mg was used in conjunction with methotrexate, improvements in test scores, including mTSS, were statistically significant.

RA-BEAM. The researchers compared baricitinib 4 mg with placebo and adalimumab in 1,305 patients. All patients maintained a background level of methotrexate to improve the efficacy of adalimumab. Consistent with previous studies, baricitinib 4 mg outperformed other therapies and placebo in improvement in ACR 20, change in DAS28-CRP, change in HAQ-DI, and SDAI remission, as well as improvements in morning joint stiffness duration and severity, worst joint pain, and worst tiredness (P less than .0001).

Despite the clear efficacy of baricitinib 4 mg, the primary issue of contention was safety and benefit-to-risk ratio. The primary safety concerns were serious infection from opportunistic pathogens, herpes zoster, various malignancies, arterial and venous thrombosis, and laboratory abnormalities including elevated platelet counts and liver test elevations.

[email protected]

The Food and Drug Administration Arthritis Advisory Committee has voted to recommend the 2-mg dose of baricitinib, an orally administered Janus kinase (JAK) inhibitor, to treat adults with moderate to severe rheumatoid arthritis who have responded inadequately or poorly to methotrexate but rejected a 4-mg dose of the same drug.

In separate votes on efficacy of the 2-mg and 4-mg doses of baricitinib (14-1 and 15-0, respectively), on their safety (9-6 and 4-11), and on their benefit-risk ratio (10-5 and 5-10), the advisory committee consistently backed the 2-mg dose, but the committee rejected the 4-mg dose despite its effectiveness in improving the symptoms of rheumatoid arthritis. Although the FDA does not always follow the advice of its advisory committees, it generally does.

The New Drug Application was resubmitted by Eli Lilly and Incyte. The proposed doses included a 2-mg once-daily dose and a 4-mg dose for some patients. The original submission was filed in January of 2016 with an indication to treat moderate to severe rheumatoid arthritis, but that application was rejected primarily because of concerns about thrombotic events. Other issues with the original application included inadequate safety exposure for the 2-mg dose of baricitinib, as well as inconsistent findings concerning the efficacy of the higher 4-mg dose.

The resubmission addressed several of the issues noted by the FDA, and changed the indication to treat patients with moderate to severe RA who have had an inadequate response to methotrexate. Along with the different indication, the dosing regimen shifted to 2 mg once daily. For patients who did not adequately respond to disease-modifying antirheumatic drugs (DMARDS) or had an intolerance for one or more of these drugs, a 4-mg dose was recommended; after disease activity had been controlled, a taper to 2 mg once daily could be considered.

Apart from changes in the drug dosage and indication, the resubmission also included accumulated safety data, comparative epidemiologic data concerning venous thromboembolism and pulmonary embolism, and efficacy analyses to support the new dosing recommendations.

“The risk-benefit ratio may be less good here,” stated Donald Miller, PharmD, a professor of pharmacy practice at North Dakota State University, Fargo. “If there is a safety issue, it’s more likely to be a problem with the 4-mg dose.”

Jon Russell, MD, PhD, medical director of Fibromyalgia Research and Consulting, San Antonio, felt that the manufacturer understood that the safety signal indicated that the benefits outweighed the risks with the 4-mg dose of baricitinib.

“The drug is efficacious in resistant rheumatoid arthritis, and rheumatoid arthritis is a devastating disease. Organs are being destroyed, joints as well as organs, and it’s war. We need to make the patient aware that it’s war and then fight it like it is,” he said.

Many of the committee members mentioned that the efficacies of the 2-mg and 4-mg doses were not in question, primarily based on the data from four phase 3 clinical trials.

The studies RA-BEACON (JADW), RA-BUILD (JADX), RA-BEGIN (JADZ), and RA-BEAM (JADV) were all randomized phase 3 trials that evaluated the efficacy of baricitinib in patients with moderate to severe RA.

RA-BEACON and RA-BUILD both had similar designs and compared 2-mg and 4-mg doses of baricitinib with placebo; the trials primarily differed in their patient populations.

RA-BEACON. Investigators looked at 527 randomized patients who had failed treatment with a biologic DMARD with nearly half failing multiple classes of this drug. The primary endpoint for this study was met, with the 4-mg dose showing superior results, compared with placebo, based on American College of Rheumatology (ACR) 20 scores (P less than .0001). As early as week 1 of the trial, both patients receiving 2 mg and those receiving 4 mg of baricitinib showed significant improvement, compared with placebo. By week 4, the 4-mg dose produced as much improvement as the 2-mg dose achieved over nearly 6 months. While the 4-mg dose was considered more effective, the 2-mg dose showed improvement in ACR 20 scores, change in Disease Activity Score 28 C-reactive protein (DAS28-CRP), and change in health assessment questionnaire disability index (HAQ-DI) (P less than .001). Neither the 4-mg nor the 2-mg dose was able to reduce Simple Disease Activity Index (SDAI) scores, a difficult endpoint to achieve, particularly in such a short time frame.

RA-BUILD. The researchers looked at patients who had failed treatment with conventional DMARDs and had not been treated with biologic DMARDS. The investigators looked at 684 randomized patients and saw similar results to RA-BEACON, with both the 2-mg and 4-mg doses displaying significant improvement in ACR 20, change in DAS28-CRP, and change in HAQ-DI, as well as SDAI remission which had been absent in RA-BEACON. Patients taking the 4-mg dose showed improvement in morning joint stiffness duration and severity (P less than .0001), as well as improvements in worst joint pain (P less than .0001) and tiredness (P less than .027).

RA-BEGIN. The investigators took a different approach and compared various drug combinations, including baricitinib 4 mg alone or in combination with oral methotrexate or in patients taking methotrexate who were DMARD-naive. Ultimately, this trial displayed that baricitinib 4 mg alone was superior to methotrexate, according to ACR 20 scores. This held true across all clinical measures at week 24 whether baricitinib was administered alone or in combination with methotrexate. As it had in the previously discussed trials, the 4-mg dose improved all of the previously mentioned test scores, compared with methotrexate (P less than .0001) except for modified Total Sharp Score (mTSS) (P = 0.158). When baricitinib 4 mg was used in conjunction with methotrexate, improvements in test scores, including mTSS, were statistically significant.

RA-BEAM. The researchers compared baricitinib 4 mg with placebo and adalimumab in 1,305 patients. All patients maintained a background level of methotrexate to improve the efficacy of adalimumab. Consistent with previous studies, baricitinib 4 mg outperformed other therapies and placebo in improvement in ACR 20, change in DAS28-CRP, change in HAQ-DI, and SDAI remission, as well as improvements in morning joint stiffness duration and severity, worst joint pain, and worst tiredness (P less than .0001).

Despite the clear efficacy of baricitinib 4 mg, the primary issue of contention was safety and benefit-to-risk ratio. The primary safety concerns were serious infection from opportunistic pathogens, herpes zoster, various malignancies, arterial and venous thrombosis, and laboratory abnormalities including elevated platelet counts and liver test elevations.

[email protected]

The Food and Drug Administration Arthritis Advisory Committee has voted to recommend the 2-mg dose of baricitinib, an orally administered Janus kinase (JAK) inhibitor, to treat adults with moderate to severe rheumatoid arthritis who have responded inadequately or poorly to methotrexate but rejected a 4-mg dose of the same drug.

In separate votes on efficacy of the 2-mg and 4-mg doses of baricitinib (14-1 and 15-0, respectively), on their safety (9-6 and 4-11), and on their benefit-risk ratio (10-5 and 5-10), the advisory committee consistently backed the 2-mg dose, but the committee rejected the 4-mg dose despite its effectiveness in improving the symptoms of rheumatoid arthritis. Although the FDA does not always follow the advice of its advisory committees, it generally does.

The New Drug Application was resubmitted by Eli Lilly and Incyte. The proposed doses included a 2-mg once-daily dose and a 4-mg dose for some patients. The original submission was filed in January of 2016 with an indication to treat moderate to severe rheumatoid arthritis, but that application was rejected primarily because of concerns about thrombotic events. Other issues with the original application included inadequate safety exposure for the 2-mg dose of baricitinib, as well as inconsistent findings concerning the efficacy of the higher 4-mg dose.

The resubmission addressed several of the issues noted by the FDA, and changed the indication to treat patients with moderate to severe RA who have had an inadequate response to methotrexate. Along with the different indication, the dosing regimen shifted to 2 mg once daily. For patients who did not adequately respond to disease-modifying antirheumatic drugs (DMARDS) or had an intolerance for one or more of these drugs, a 4-mg dose was recommended; after disease activity had been controlled, a taper to 2 mg once daily could be considered.

Apart from changes in the drug dosage and indication, the resubmission also included accumulated safety data, comparative epidemiologic data concerning venous thromboembolism and pulmonary embolism, and efficacy analyses to support the new dosing recommendations.

“The risk-benefit ratio may be less good here,” stated Donald Miller, PharmD, a professor of pharmacy practice at North Dakota State University, Fargo. “If there is a safety issue, it’s more likely to be a problem with the 4-mg dose.”

Jon Russell, MD, PhD, medical director of Fibromyalgia Research and Consulting, San Antonio, felt that the manufacturer understood that the safety signal indicated that the benefits outweighed the risks with the 4-mg dose of baricitinib.

“The drug is efficacious in resistant rheumatoid arthritis, and rheumatoid arthritis is a devastating disease. Organs are being destroyed, joints as well as organs, and it’s war. We need to make the patient aware that it’s war and then fight it like it is,” he said.

Many of the committee members mentioned that the efficacies of the 2-mg and 4-mg doses were not in question, primarily based on the data from four phase 3 clinical trials.

The studies RA-BEACON (JADW), RA-BUILD (JADX), RA-BEGIN (JADZ), and RA-BEAM (JADV) were all randomized phase 3 trials that evaluated the efficacy of baricitinib in patients with moderate to severe RA.

RA-BEACON and RA-BUILD both had similar designs and compared 2-mg and 4-mg doses of baricitinib with placebo; the trials primarily differed in their patient populations.

RA-BEACON. Investigators looked at 527 randomized patients who had failed treatment with a biologic DMARD with nearly half failing multiple classes of this drug. The primary endpoint for this study was met, with the 4-mg dose showing superior results, compared with placebo, based on American College of Rheumatology (ACR) 20 scores (P less than .0001). As early as week 1 of the trial, both patients receiving 2 mg and those receiving 4 mg of baricitinib showed significant improvement, compared with placebo. By week 4, the 4-mg dose produced as much improvement as the 2-mg dose achieved over nearly 6 months. While the 4-mg dose was considered more effective, the 2-mg dose showed improvement in ACR 20 scores, change in Disease Activity Score 28 C-reactive protein (DAS28-CRP), and change in health assessment questionnaire disability index (HAQ-DI) (P less than .001). Neither the 4-mg nor the 2-mg dose was able to reduce Simple Disease Activity Index (SDAI) scores, a difficult endpoint to achieve, particularly in such a short time frame.

RA-BUILD. The researchers looked at patients who had failed treatment with conventional DMARDs and had not been treated with biologic DMARDS. The investigators looked at 684 randomized patients and saw similar results to RA-BEACON, with both the 2-mg and 4-mg doses displaying significant improvement in ACR 20, change in DAS28-CRP, and change in HAQ-DI, as well as SDAI remission which had been absent in RA-BEACON. Patients taking the 4-mg dose showed improvement in morning joint stiffness duration and severity (P less than .0001), as well as improvements in worst joint pain (P less than .0001) and tiredness (P less than .027).

RA-BEGIN. The investigators took a different approach and compared various drug combinations, including baricitinib 4 mg alone or in combination with oral methotrexate or in patients taking methotrexate who were DMARD-naive. Ultimately, this trial displayed that baricitinib 4 mg alone was superior to methotrexate, according to ACR 20 scores. This held true across all clinical measures at week 24 whether baricitinib was administered alone or in combination with methotrexate. As it had in the previously discussed trials, the 4-mg dose improved all of the previously mentioned test scores, compared with methotrexate (P less than .0001) except for modified Total Sharp Score (mTSS) (P = 0.158). When baricitinib 4 mg was used in conjunction with methotrexate, improvements in test scores, including mTSS, were statistically significant.

RA-BEAM. The researchers compared baricitinib 4 mg with placebo and adalimumab in 1,305 patients. All patients maintained a background level of methotrexate to improve the efficacy of adalimumab. Consistent with previous studies, baricitinib 4 mg outperformed other therapies and placebo in improvement in ACR 20, change in DAS28-CRP, change in HAQ-DI, and SDAI remission, as well as improvements in morning joint stiffness duration and severity, worst joint pain, and worst tiredness (P less than .0001).

Despite the clear efficacy of baricitinib 4 mg, the primary issue of contention was safety and benefit-to-risk ratio. The primary safety concerns were serious infection from opportunistic pathogens, herpes zoster, various malignancies, arterial and venous thrombosis, and laboratory abnormalities including elevated platelet counts and liver test elevations.

[email protected]

MADRID – A targeted antibiotic strategy that employed ertapenem in carriers of extended-spectrum beta-lactamase–producing Enterobacteriaceae reduced infections after colorectal surgery by 41%, compared with routine treatment with cefuroxime and metronidazole.

The strategy was even more effective at preventing surgical site infections caused by ESBL-producing bacteria, cutting the rate by 87%, Amir Nutman, MD, said at the European Congress of Clinical Microbiology and Infectious Diseases.

Michele G. Sullivan/MDedge News

The primary outcome was surgical site infection at 30 days. Secondary outcomes were the type of any surgical site infection (superficial, deep, or organ/space), and infections caused by ESBL-producing bacteria.

ESBL screening was carried out on 3,626 patients; carriage prevalence was 13.8%, but varied by center from 9% to 29%. Of the carriers, 468 were included in the study; 247 received routine prophylaxis and 221 received ertapenem.

Patients were a mean of 63 years old; 98% were living at home before admission. About 20% had diabetes; 5% had some type of immunodeficiency. The most common surgical indication was colon cancer (68%), and about a third had undergone prior colon surgery. Most of the surgeries were open, and about half involved a colectomy.

Patients in the ertapenem group had overall better scores on the National Nosocomial Infections Surveillance Basic SSI Risk Index and were less likely to have an intraoperative finding of colon dilation (20.8% vs. 27%).There were no other clinically compelling intraoperative differences between the two groups, including bleeding, bowel spillage, the need for drains, or stoma placement.

Patients who received prophylactic ertapenem had significantly better 30-day outcomes on all measures of infection than did patients who had standard prophylaxis, Dr. Nutman said.

There were 34 surgical site infections in the routine prophylaxis group and 19 in the ertapenem group. Among these, 17 in the routine group and three in the ertapenem group were caused by ESBL-producing bacteria. The ESBL-positive infections were as follows:

• E. coli (thirteen in the routine and one in the ertapenem group).
• Klebsiella species (four and one, respectively).
• Proteus species (one in the ertapenem group).

Other infections were caused by ESBL-nonproducers, including E. coli, Klebsiella, Proteus, Enterococci, Pseudomonas aeruginosa, Staphylococcus aureus, and other unspecified organisms. Polymicrobial infections occurred in 25 patients.

In an analysis that controlled for National Nosocomial Infections Surveillance score and colon dilation, patients who received ertapenem were 41% less likely to develop any surgical site infection (15.8% vs. 22.7%; odds ratio, 0.59); 17% less likely to develop a deep infection (9.5% vs. 11.3%; OR, 0.83); and 87% less likely to develop an infection caused by an ESBL-producing bacteria (0.9% vs. 6.5%; OR, 0.13).

Dr. Nutman made no financial declarations.

[email protected]

SOURCE: Nutman et al. ECCMID 2018, Abstract O1129.

MADRID – A targeted antibiotic strategy that employed ertapenem in carriers of extended-spectrum beta-lactamase–producing Enterobacteriaceae reduced infections after colorectal surgery by 41%, compared with routine treatment with cefuroxime and metronidazole.

The strategy was even more effective at preventing surgical site infections caused by ESBL-producing bacteria, cutting the rate by 87%, Amir Nutman, MD, said at the European Congress of Clinical Microbiology and Infectious Diseases.

Michele G. Sullivan/MDedge News

The primary outcome was surgical site infection at 30 days. Secondary outcomes were the type of any surgical site infection (superficial, deep, or organ/space), and infections caused by ESBL-producing bacteria.

ESBL screening was carried out on 3,626 patients; carriage prevalence was 13.8%, but varied by center from 9% to 29%. Of the carriers, 468 were included in the study; 247 received routine prophylaxis and 221 received ertapenem.

Patients were a mean of 63 years old; 98% were living at home before admission. About 20% had diabetes; 5% had some type of immunodeficiency. The most common surgical indication was colon cancer (68%), and about a third had undergone prior colon surgery. Most of the surgeries were open, and about half involved a colectomy.

Patients in the ertapenem group had overall better scores on the National Nosocomial Infections Surveillance Basic SSI Risk Index and were less likely to have an intraoperative finding of colon dilation (20.8% vs. 27%).There were no other clinically compelling intraoperative differences between the two groups, including bleeding, bowel spillage, the need for drains, or stoma placement.

Patients who received prophylactic ertapenem had significantly better 30-day outcomes on all measures of infection than did patients who had standard prophylaxis, Dr. Nutman said.

There were 34 surgical site infections in the routine prophylaxis group and 19 in the ertapenem group. Among these, 17 in the routine group and three in the ertapenem group were caused by ESBL-producing bacteria. The ESBL-positive infections were as follows:

• E. coli (thirteen in the routine and one in the ertapenem group).
• Klebsiella species (four and one, respectively).
• Proteus species (one in the ertapenem group).

Other infections were caused by ESBL-nonproducers, including E. coli, Klebsiella, Proteus, Enterococci, Pseudomonas aeruginosa, Staphylococcus aureus, and other unspecified organisms. Polymicrobial infections occurred in 25 patients.

In an analysis that controlled for National Nosocomial Infections Surveillance score and colon dilation, patients who received ertapenem were 41% less likely to develop any surgical site infection (15.8% vs. 22.7%; odds ratio, 0.59); 17% less likely to develop a deep infection (9.5% vs. 11.3%; OR, 0.83); and 87% less likely to develop an infection caused by an ESBL-producing bacteria (0.9% vs. 6.5%; OR, 0.13).

Dr. Nutman made no financial declarations.

[email protected]

SOURCE: Nutman et al. ECCMID 2018, Abstract O1129.

MADRID – A targeted antibiotic strategy that employed ertapenem in carriers of extended-spectrum beta-lactamase–producing Enterobacteriaceae reduced infections after colorectal surgery by 41%, compared with routine treatment with cefuroxime and metronidazole.

The strategy was even more effective at preventing surgical site infections caused by ESBL-producing bacteria, cutting the rate by 87%, Amir Nutman, MD, said at the European Congress of Clinical Microbiology and Infectious Diseases.

Michele G. Sullivan/MDedge News

The primary outcome was surgical site infection at 30 days. Secondary outcomes were the type of any surgical site infection (superficial, deep, or organ/space), and infections caused by ESBL-producing bacteria.

ESBL screening was carried out on 3,626 patients; carriage prevalence was 13.8%, but varied by center from 9% to 29%. Of the carriers, 468 were included in the study; 247 received routine prophylaxis and 221 received ertapenem.

Patients were a mean of 63 years old; 98% were living at home before admission. About 20% had diabetes; 5% had some type of immunodeficiency. The most common surgical indication was colon cancer (68%), and about a third had undergone prior colon surgery. Most of the surgeries were open, and about half involved a colectomy.

Patients in the ertapenem group had overall better scores on the National Nosocomial Infections Surveillance Basic SSI Risk Index and were less likely to have an intraoperative finding of colon dilation (20.8% vs. 27%).There were no other clinically compelling intraoperative differences between the two groups, including bleeding, bowel spillage, the need for drains, or stoma placement.

Patients who received prophylactic ertapenem had significantly better 30-day outcomes on all measures of infection than did patients who had standard prophylaxis, Dr. Nutman said.

There were 34 surgical site infections in the routine prophylaxis group and 19 in the ertapenem group. Among these, 17 in the routine group and three in the ertapenem group were caused by ESBL-producing bacteria. The ESBL-positive infections were as follows:

• E. coli (thirteen in the routine and one in the ertapenem group).
• Klebsiella species (four and one, respectively).
• Proteus species (one in the ertapenem group).

Other infections were caused by ESBL-nonproducers, including E. coli, Klebsiella, Proteus, Enterococci, Pseudomonas aeruginosa, Staphylococcus aureus, and other unspecified organisms. Polymicrobial infections occurred in 25 patients.

In an analysis that controlled for National Nosocomial Infections Surveillance score and colon dilation, patients who received ertapenem were 41% less likely to develop any surgical site infection (15.8% vs. 22.7%; odds ratio, 0.59); 17% less likely to develop a deep infection (9.5% vs. 11.3%; OR, 0.83); and 87% less likely to develop an infection caused by an ESBL-producing bacteria (0.9% vs. 6.5%; OR, 0.13).

Dr. Nutman made no financial declarations.

[email protected]

SOURCE: Nutman et al. ECCMID 2018, Abstract O1129.

Registration Now Open for 2018 ACS Quality and Safety Conference

Health care professionals dedicated to raising the bar on the quality of surgical care and patient safety are invited to attend the 2018 American College of Surgeons (ACS) Quality and Safety Conference, July 21–24 at the Hyatt Regency Orlando, FL.

• Trauma Quality Programs, including Pediatrics, Trauma Center Verification, the Trauma Quality Improvement Program, and Performance Improvement and Patient Safety

The conference theme, Partnering for Improvement, will set the tone for the meeting, as presenters and organizers strive to achieve the following:

• Provide a professional forum to discuss and apply the most recent knowledge on quality and safety initiatives in surgery

• Present methods used to analyze data from ACS Quality Programs and demonstrate practical ways to use the data for quality improvement (QI)

• Assist hospitals and providers in managing, analyzing, and interpreting data

• Enhance the learning experience by offering breakout sessions that educate attendees on topic areas of their interest

An additional track will be dedicated to Optimal Resources for Surgical Quality and Safety, the “red book,” which will explore concepts and resources from the manual, information on QI tools, methodology, nomenclature, and organizational design and infrastructure. Other notable sessions will highlight important clinical topics, including efficiency in surgical care, the opioid epidemic, and preoperative optimization.

Keynote speaker Rolf Benirschke, a former placekicker in the NFL, will discuss his experience collapsing on a cross-country team flight while battling ulcerative colitis and subsequently undergoing two emergency operations within six days.

Further details about the conference can be viewed on the Quality and Safety Conference website at www.facs.org/quality-programs/quality-safety-conference.

Registration Now Open for 2018 ACS Quality and Safety Conference

Health care professionals dedicated to raising the bar on the quality of surgical care and patient safety are invited to attend the 2018 American College of Surgeons (ACS) Quality and Safety Conference, July 21–24 at the Hyatt Regency Orlando, FL.

• Trauma Quality Programs, including Pediatrics, Trauma Center Verification, the Trauma Quality Improvement Program, and Performance Improvement and Patient Safety

The conference theme, Partnering for Improvement, will set the tone for the meeting, as presenters and organizers strive to achieve the following:

• Provide a professional forum to discuss and apply the most recent knowledge on quality and safety initiatives in surgery

• Present methods used to analyze data from ACS Quality Programs and demonstrate practical ways to use the data for quality improvement (QI)

• Assist hospitals and providers in managing, analyzing, and interpreting data

• Enhance the learning experience by offering breakout sessions that educate attendees on topic areas of their interest

An additional track will be dedicated to Optimal Resources for Surgical Quality and Safety, the “red book,” which will explore concepts and resources from the manual, information on QI tools, methodology, nomenclature, and organizational design and infrastructure. Other notable sessions will highlight important clinical topics, including efficiency in surgical care, the opioid epidemic, and preoperative optimization.

Keynote speaker Rolf Benirschke, a former placekicker in the NFL, will discuss his experience collapsing on a cross-country team flight while battling ulcerative colitis and subsequently undergoing two emergency operations within six days.

Further details about the conference can be viewed on the Quality and Safety Conference website at www.facs.org/quality-programs/quality-safety-conference.

Registration Now Open for 2018 ACS Quality and Safety Conference

Health care professionals dedicated to raising the bar on the quality of surgical care and patient safety are invited to attend the 2018 American College of Surgeons (ACS) Quality and Safety Conference, July 21–24 at the Hyatt Regency Orlando, FL.

• Trauma Quality Programs, including Pediatrics, Trauma Center Verification, the Trauma Quality Improvement Program, and Performance Improvement and Patient Safety

The conference theme, Partnering for Improvement, will set the tone for the meeting, as presenters and organizers strive to achieve the following:

• Provide a professional forum to discuss and apply the most recent knowledge on quality and safety initiatives in surgery

• Present methods used to analyze data from ACS Quality Programs and demonstrate practical ways to use the data for quality improvement (QI)

• Assist hospitals and providers in managing, analyzing, and interpreting data

• Enhance the learning experience by offering breakout sessions that educate attendees on topic areas of their interest

An additional track will be dedicated to Optimal Resources for Surgical Quality and Safety, the “red book,” which will explore concepts and resources from the manual, information on QI tools, methodology, nomenclature, and organizational design and infrastructure. Other notable sessions will highlight important clinical topics, including efficiency in surgical care, the opioid epidemic, and preoperative optimization.

Keynote speaker Rolf Benirschke, a former placekicker in the NFL, will discuss his experience collapsing on a cross-country team flight while battling ulcerative colitis and subsequently undergoing two emergency operations within six days.

Further details about the conference can be viewed on the Quality and Safety Conference website at www.facs.org/quality-programs/quality-safety-conference.

LOS ANGELES – Women treated surgically and with hormones for endometriosis may continue to experience pain, say investigators, and that pain frequently extends beyond the pelvis.

At the annual meeting of the American Academy of Neurology, Barbara Karp, MD, of the National Institute of Neurological Disorders and Stroke, presented results from an ongoing randomized trial of women with endometriosis receiving botulinum toxin to treat endometriosis-related chronic pelvic pain and pelvic spasm.

designer491/Thinkstock

All subjects had myofascial dysfunction. Most reported headaches and half reported orofacial pain, while 13 subjects reported myofascial trigger points in all the 26 spots assessed, which included head and facial muscles, shoulder and back muscles, and muscles in the buttocks, abdomen, and upper legs.

Dr. Karp said her group hypothesized that for patients with endometriosis, the widespread pain seen in the study “probably has some origin in sensitization initiated by pain associated with the endometriosis lesions, and that gives us a mechanism to think about peripheral and central sensitization.” But she noted that such sensitization can be easily missed in the clinic.

“One of the things that’s really underappreciated is how much women with chronic pelvic pain have pain elsewhere. So the neurologist or pain specialist may say, ‘that’s not my body territory, there’s something going on with your pelvis.’ And the gynecologist may be focused on the endometriosis and the endometriosis lesions. So you have these women with really widespread pain problems whose care is being fractionated.”

In another aspect of the study she also presented at the meeting, Dr. Karp, a neurologist who has studied the therapeutic use of neurotoxins such as botulinum for 30 years, showed results from an open-label extension of a randomized trial of botulinum toxin injections to treat pelvic spasm in the same cohort of women with confirmed endometriosis and confirmed pelvic muscle spasm.

“It’s an area of the body neurologists don’t feel comfortable injecting, and I don’t necessarily feel comfortable doing it myself,” Dr. Karp said.

The researchers had to develop their own procedure because at the time they started the research there was almost nothing in the literature on how to inject botulinum toxin for pelvic pain in women. “People in different specialties have been doing it [to relieve pelvic pain] and it’s really widespread, but they’re doing it all different ways,” Dr. Karp said. “We’re hoping to find a best approach.”

Dr. Karp and her colleagues’ research is supported by the NINDS and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. OnabotulinumtoxinA for the clinical trial is supplied by Allergan. Dr. Karp has received research support from Allergan and Merz.

SOURCE: Karp B et al. AAN 2018, Abstract P2.096; Karp B et al. AAN 2018, Abstract P2.098.

LOS ANGELES – Women treated surgically and with hormones for endometriosis may continue to experience pain, say investigators, and that pain frequently extends beyond the pelvis.

At the annual meeting of the American Academy of Neurology, Barbara Karp, MD, of the National Institute of Neurological Disorders and Stroke, presented results from an ongoing randomized trial of women with endometriosis receiving botulinum toxin to treat endometriosis-related chronic pelvic pain and pelvic spasm.

designer491/Thinkstock

All subjects had myofascial dysfunction. Most reported headaches and half reported orofacial pain, while 13 subjects reported myofascial trigger points in all the 26 spots assessed, which included head and facial muscles, shoulder and back muscles, and muscles in the buttocks, abdomen, and upper legs.

Dr. Karp said her group hypothesized that for patients with endometriosis, the widespread pain seen in the study “probably has some origin in sensitization initiated by pain associated with the endometriosis lesions, and that gives us a mechanism to think about peripheral and central sensitization.” But she noted that such sensitization can be easily missed in the clinic.

“One of the things that’s really underappreciated is how much women with chronic pelvic pain have pain elsewhere. So the neurologist or pain specialist may say, ‘that’s not my body territory, there’s something going on with your pelvis.’ And the gynecologist may be focused on the endometriosis and the endometriosis lesions. So you have these women with really widespread pain problems whose care is being fractionated.”

In another aspect of the study she also presented at the meeting, Dr. Karp, a neurologist who has studied the therapeutic use of neurotoxins such as botulinum for 30 years, showed results from an open-label extension of a randomized trial of botulinum toxin injections to treat pelvic spasm in the same cohort of women with confirmed endometriosis and confirmed pelvic muscle spasm.

“It’s an area of the body neurologists don’t feel comfortable injecting, and I don’t necessarily feel comfortable doing it myself,” Dr. Karp said.

The researchers had to develop their own procedure because at the time they started the research there was almost nothing in the literature on how to inject botulinum toxin for pelvic pain in women. “People in different specialties have been doing it [to relieve pelvic pain] and it’s really widespread, but they’re doing it all different ways,” Dr. Karp said. “We’re hoping to find a best approach.”

Dr. Karp and her colleagues’ research is supported by the NINDS and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. OnabotulinumtoxinA for the clinical trial is supplied by Allergan. Dr. Karp has received research support from Allergan and Merz.

SOURCE: Karp B et al. AAN 2018, Abstract P2.096; Karp B et al. AAN 2018, Abstract P2.098.

LOS ANGELES – Women treated surgically and with hormones for endometriosis may continue to experience pain, say investigators, and that pain frequently extends beyond the pelvis.

At the annual meeting of the American Academy of Neurology, Barbara Karp, MD, of the National Institute of Neurological Disorders and Stroke, presented results from an ongoing randomized trial of women with endometriosis receiving botulinum toxin to treat endometriosis-related chronic pelvic pain and pelvic spasm.

designer491/Thinkstock

All subjects had myofascial dysfunction. Most reported headaches and half reported orofacial pain, while 13 subjects reported myofascial trigger points in all the 26 spots assessed, which included head and facial muscles, shoulder and back muscles, and muscles in the buttocks, abdomen, and upper legs.

Dr. Karp said her group hypothesized that for patients with endometriosis, the widespread pain seen in the study “probably has some origin in sensitization initiated by pain associated with the endometriosis lesions, and that gives us a mechanism to think about peripheral and central sensitization.” But she noted that such sensitization can be easily missed in the clinic.

“One of the things that’s really underappreciated is how much women with chronic pelvic pain have pain elsewhere. So the neurologist or pain specialist may say, ‘that’s not my body territory, there’s something going on with your pelvis.’ And the gynecologist may be focused on the endometriosis and the endometriosis lesions. So you have these women with really widespread pain problems whose care is being fractionated.”

In another aspect of the study she also presented at the meeting, Dr. Karp, a neurologist who has studied the therapeutic use of neurotoxins such as botulinum for 30 years, showed results from an open-label extension of a randomized trial of botulinum toxin injections to treat pelvic spasm in the same cohort of women with confirmed endometriosis and confirmed pelvic muscle spasm.

“It’s an area of the body neurologists don’t feel comfortable injecting, and I don’t necessarily feel comfortable doing it myself,” Dr. Karp said.

The researchers had to develop their own procedure because at the time they started the research there was almost nothing in the literature on how to inject botulinum toxin for pelvic pain in women. “People in different specialties have been doing it [to relieve pelvic pain] and it’s really widespread, but they’re doing it all different ways,” Dr. Karp said. “We’re hoping to find a best approach.”

Dr. Karp and her colleagues’ research is supported by the NINDS and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. OnabotulinumtoxinA for the clinical trial is supplied by Allergan. Dr. Karp has received research support from Allergan and Merz.

SOURCE: Karp B et al. AAN 2018, Abstract P2.096; Karp B et al. AAN 2018, Abstract P2.098.